Letuda 2020

Letuda’s Note 2020
OVERVIEW
Symptoms/ history/ mode of presentation of ANY DISEASE
A= Asymptomatic!!
 Incidentally diagnosed….”literally NO symptoms” ANYWHERE in the body
 NOT literally asymptomatic….ASYMPTOMATIC from point of view of “affected/”culprit” organs/system
but SYMPTOMATIC of another system/organ. This occurs when the EFFECT(s) of
the disease of a particular organ AFFECTS another organ before affecting the primary organ(complicated English
isn’t it!!)
Cardio-respiratory: Gasrtointestinal( includes hepatobilary):
Angina (ischaemic pain) Abdominal pain/discomfort
Breathlessness Abdominal distension
fluid/fat/flatus/feces/fetus
(transient)Black out (syncope) Abdominal swelling….
Chest pain (other than ischaemic pain) Appetite loss
Collapse(= sudden death) Body weight loss
Cough (dry/ expectoration) Bloating (Borborygmi)
Dizziness Constipation
Edema Diarrhoea
Encephalopathy Emesis
Fever Encephalopathy
Galloping of heart (= palpitation) Fever
Hemoptysis Flatulence
GI bleed: hematemesis/melaena/Fresh bleed PR
Heartburn
Urogenital Icterus...can be “hepato” or “biliary” pathology!!
Abdominal pain: Loin pain= Renal
Absence of urine: may be Anterior abdominal pain:
 Anuria OR  ureteric
 Acute retention  Bladder (Suprapubic/infraumbilical
Bleeding: Hematuria
Bladder disturbance:
 Irritative symptoms Obstructive uropathy symptoms
1. Increased frequency of urination 1. Poor stream
2. Increased urgency of urination 2. Retention
3. Painful urination/Dysuria 3. Overflow incontinence
Cycle disturbance 4. Straining
Decreased urine output
Encephalopathy
Fever
Neuro:
Altered sensorium Dysphonia
Altered sensation Deviation of face
Body part weakness: UL and/or LL and/or Face Dribbling of saliva/food
Bladder & bowel disturbance: Incontinence Encephalopathy
Black out Fever
Convulsion GCS: low
Dysarthria Headache
Diplopia
Hemato:
Many hematological diseases often present with ≥ 1 of these 4 phenomena
Anaemia: ≥ 1 of these
 Asymptomatic  Dizziness
 Anaemic look  Exercise intolerance
 Breathlessness  Energy lack
 Cardiac: palpitation  Fatigue
Neutropenia: any 1 of these
 Asymptomatic
 Bacteremia/ “Candida” (Fungemia): Febrile neutropenic: Fever +/‐ focal manifestation of infection
Thrombocytopenia/Coagulopathy: any 1 of these
Asymptomatic
Bleeding:
 spontaneous or prolonged bleeding after minor injury
 Sites:
1. Superficial: Purpura/ Gum bleeding/ Epistaxis
2. Deep/Internal hemorrhage: GI/ GU/ ICH/Hemarthrosis
Organomegaly: Hepato and/or Splenomegaly
Encephalopathy:
Dysfunctioning of the brain by some agent or condition which can be……
1. Diseases/condition Intrinsic to the brain: ANY brain disease So “E”= Encephalopathy
2. Diseases/condition Extrinsic to the brain (they can cause brain dysfunction) is there in many systems
Deranged Biochemical environment:
1. Na: low or high
2. Glucose: low or high ANY enephalopthic patient: C/F
3. Ca: high A. Altered sensorium
“Toxins” accumulating in the system B. Behavioral disturbance
 Organ that clears off toxin malfunctioning C. Confusion, Coma, Convulsion
1. Kidney failure: (EXCRETES metabolic waste/toxins) D. Delirium
2. Liver failure: (DETOXIFIES metabolic waste/toxins) E. Etiology related manifestation
3. Lung Failure: (ELIMINATES CO2) F. Flapping tremor( in some patients)
 Overproduction of toxins: Septicemia G. ↓GCS
 Overdose of drugs: Sedatives/ Opioids etc.
Hypovolemia/Dehydration:
Blood loss Causes can be DIVERSE Fluid loss
Visible/Obvious loss Invisible/Occult loss Visible/Obvious loss Invisible/Occult loss

Bleeding can be seen Internal hemorrhage fluid loss can be seen Concealed loss
From ANYWHERE Concealed bleeding Diarrhoea/Vomiting “Third spacing”
GI tract Ruptured ectopic Serous cavities Septicemia Acute Pancreatitis
Manifestations: Depends on SEVERITY of blood/fluid loss- ≥ 1 of the followings
Asymptomatic Cardiac: Tachycardia
BP‐ Decreased & Dark urine output Degree of “B/C/D” will vary
 Normal with Postural hypotension Dry skin & mucus membrane from patient to patient
 Low Etiology: f/o underlying cause depending on the severity
Capillary refill time: prolonged
Investigations:
1.”Ganga”!!.....: Blood investigations “Regional” material
2. “Regional” material: Brain: CSF
 “naturally” flowing fluid: “secretion”or “excretion” Throat: Swab
 “accumulated” material Respiratory: Sputum
3. Imaging: Pleura: Pleural fluid
Cardiac: Pericardial fluid
 “External camera”: Non invasive imaging: Xray/ USG/ CT/MRI
GI: Feces
 ”Selfie stick with camera”: Endoscopy
Peritoneum: Ascitic fluid
Utility of Endoscopy Bronchoscope Urinary: Urine
Diagnostic: Upper & lower GI Endoscope Genital: Swab/discharge
● Visualisation: ‘pathology’ diagnosis Cystoscope Abscess/Ulcer: Pus/ Discharge
● Taking Biopsy of the pathology Hysteroscope Joint: Synovial fluid
Therapeutic: Interventional treatment
4. Tissue: Biopsy/ FNAC

 Radio imaging guided FNAC: “juice”
 Endoscopic Biopsy: “bite”
 Surgical
General discussion on different types of investigations
“Universal” Blood investigations:
1. CBC/CRP 2. Urea/Creatinine/ Na/K
CBC/CRP: As alteration of these parameters often occurs in VARIETIES of diseases of MANY systems/organs.
Urea/ Creatinine which are markers of KIDNEY FUNCTION are often abnormal in many “NON‐KIDNEY”
diseases as these conditions may affect/alter kidney function.
Na, K: As alteration of these parameters can and often occurs in VARIETIES of diseases of MANY systems/organs.
Infection related BLOOD tests

Because infection can occur ANYWHERE, so for ANY system these are relevant blood parameters…..
Infection by micro-organism (BACTERIA/VIRUS/FUNGI/PARASITE)
Inflammmatory response Microorganism in the bloodstream
HIGH “inflammatory markers” “Capturing” Microorganism

1.CBC: WBC count 1.Blood C/S (includes staining+ culture +drug Sensitivity if Culture +ve
2.CRP 2.“Imprint” of Microorganism in blood: DNA/RNA/Antigen/Antibody
3.Procalcitonin
WBC & CRP Procalcitonin
High in Non‐bacterial inflammation AS WELL Bacteria specific marker
Procalcitonin(PCT): Normal Serum concentration is extremely low or even immeasurable.
In systemic inflammation, particularly in bacterial infections, under the influence of inflammatory cytokines
and bacterial endotoxin, it is produced in a number of tissues and goes in circulation & its level can increase as
early as even 2‐4 hours after stimulation. In comparison, the level of CRP starts to rise 12‐24 hours after
stimulation. PCT is a stable marker, whose concentration is not affected by neutropenia, immunodeficiency
conditions which is not the case with CRP.
“Regional” Materials
Brain: CSF Utility of “regional material” tests

Respiratory: Infection/inflammation suspected:
 Sputum  “regional material” tested for:
 Pleural fluid a. Inflammatory markers: WBC count/ Protein
Cardiac: Pericardial fluid b. Organism: stain/Culture/”Imprint”: DNA/RNA/Antigen/Antibody
GI:
Malignancy suspected:
 Feces
 “regional material” tested for: abnormal Cytology
 Ascitic fluid
Urinary: Urine
Genital: Swab/discharge
Abscess/Ulcer: Pus/ Discharge
Joint: Synovial fluid
IMAGING
Non- invasive: Radioimaging
Organs/Soft tissue/Bones/Joints Needs to imaged Blood vessels (Artery/veins) needs to be imaged
1. Xray SAME IMAGING studies with a
2. USG Better technology, so “picture “SPECIAL MODE/TECHNIQUE” which
3. CT quality” improves & so…. highlights the vessels……so the name becomes
4. MRI It seems the radiological information 1.USG Doppler: Arterial or Venous
they give also get better BUT this is 2.CT Angio/Venogram
NOT the fact always 3. MR Angio/Venogram
Between them which one is the BEST that
Situations where these are required
depends on 2 factors:
 Suspected THORMBUS in Artery/vein
1.Which area/structure is being imaged
 Suspected NARROWING of Artery/vein
2. What type of pathology is there
 Suspected ANEURYSM of Artery
PET-CT scan whole body

Special scan after administering Radiolabeled Glucose molecule
Metabolically ACTIVE tissues EXCESSIVELY uptake this glucose

Scan image: These areas look BRIGHTER (“lit up”)
Malignant tissues Tissues with ongoing significant Infection
Helps to localize the primary & metastatic areas Helps to localize any “hidden” focus of infection
So, PET‐CT nowadays is increasingly getting used in some patients of Fever of Unknown origin
Endoscopic imaging
Needs a “tube with natural orifice” to insert the “selfie stick- camera”
So, Endoscopy can be done for
GI tract: Upper & lower GI Endoscope Arteries!!!....are tubes which can be
Respiratory tract: Bronchoscope punctured to get into them….So a fine
Urinary tract: Cystoscope catheter connected with a camera (as
Reproductive tract: Hysteroscope if “endoscopy”) can be inserted into
arteries. This is Angiography!!
IMAGING of blood vessels
Non invasive technique/tests Invasive technique/tests

1.USG Doppler: Arterial or Venous Conventional/Catheter angiography
2.CT Angio/Venogram
3. MR Angio/Venogram
Radioimaging: Overview in relation to DIAGNOSIS
Radiographic Appearance of an area in MANY DISEASES of that area
Abnormal appearance characteristic of a particular PATHOLOGY/DISEASE
2 very common diseases that radio-imaging appearance helps to diagnose
Infective pathology Tumor (benign/malignant)

further confirmation
1.”Regional” material: MICROBIOLOGICAL tests Microscopic examination for ABNORMAL cells
2. Biopsy/FNAC: MICROBIOLOGICAL tests Microscopic examination for ABNORMAL cells
Biopsy/ FNAC
[
Often required to confirm 2 types of diseases
Most of the time their SUSPICION arises from CLINICO-RADIOLOGICAL information
INFLAMMATORY TUMOR/MASS/ULCER
Infective etiology Non- infective etiology Benign Malignant
ALL CONFIRMED BY following 2 tests of biopsy/FNAC sample

1.Microbiological tests 2.Histopathological examination
(Stain & Culture) ( Microscopic examination)
Histopathological examination: Even in infective etiology microscopic appearance of the tissue helps in
diagnosis: Plenty of neutrophil/Necrotic material/lymphocyte/ caseating granuloma
Biopsy is NOT for suspected malignancy ONLY!!
ABG
MANY CONDITIONS/DISEASES: Imbalance of Acid-Base equilibrium
Acidosis Alkalosis
Overproduction of Overproduction or Under-excretion Excessive wash out of Excessive loss of

Respiratory acid (CO2) of Metabolically generated acids Respiratory acid (CO2) Metabolically generated acid
Respiratory acidosis Metabolic acidosis Respiratory alkalosis Metabolic alkalosis
ABG tells us pH: Acidosis/Alkalosis; PCO2, PO2‐ “Gas”; H+/HCO3-/Lactate‐ “Acid‐ Base”‐ So ABG= “Acid Base Gas”!!
ABG diagnoses the (acid‐base‐ gaseous) environmental change, It can not diagnose the condition responsible for it
BUT knowing this environmental “pollution” is IMMENSELY important because of 2 reasons
1.Significant Acidosis (mainly), to some extent alkalosis as well can be LIFE THREATENING
2. So, the “environment” is often URGENTLY treated even before commencement of treatment of the disease
responsible for it. So ABG is often the 1st test many patients will have
Acidosis more dangerous than Alkalosis
Conditions causing Acidosis “MUCH MUCH MUCH MORE COMMON” than conditions causing Alkalosis!!
ORGAN/SYSTEM wise investigations
NOT EVERY patient will require ALL of these investigations…….
Respiratory:
1. Blood:
 CBC+ CRP ABG tells us…….
 ABG: pH, PCO2, PO2 pH: Acidosis/Alkalosis
 Blood C/S PCO2, PO2‐ “Gas”
 Procalcitonin (PCT) H+/HCO3-/Lactate‐ “Acid‐ Base”
2.Sputum: So ABG= “Acid Base Gas”!!
 Gram stain/ZN stain/Fungal stain
 Culture: Bacterial/Fungal
 “Imprint”: TB‐PCR( Genexpert TB)
3. Imaging: 1. Radioimaging 2. Endoscopic Invasive
Chest xray Bronchoscopy
USG chest
CT
MRI
4. Pulmonary function test Brain Natriuretic Peptide (BNP): synthesis and
5. Lung biopsy/ FNAC secretion by ventricular myocardium
Cardio: Synthesized as proBNP & upon release into the
1.Blood: circulation cleaved into BNP and NT‐proBNP
 CBC/CRP (N‐terminal fragment)
 Blood C/S Physiological effects: natriuresis/diuresis,
peripheral vasodilatation, and inhibition of the
 Urea/Creatinine/Na/K
renin–angiotensin–aldosterone system (RAAS)
 Hypoxia: ABG(LHF leads to Pulmonary edema!!)
and inhibition of the sympathetic nervous
 Arrhythmia: K, Ca, Mg (“Arrhythmogenic” electrolytes) system (SNS)
 Ischaemia: Cardiac enzymes: TropI/T; CK, CK‐MB So in Cardiac stress which leads to
 Cardiac failure: BNP/ Pro BNP/ NT Pro BNP Dysfunction/failure as a PHYSIOLOGICAL
 Cardiac risk profile/ Cardiovascular risk stratification: COMPENSATORY mechanism BNP release is
1. Glycemic profile 2. Lipid profile increased to AUGMENT it’s effects (see above)-
2.Imaging: all of which “offload” the heart
Chest Xray (Left heart failure leads to pulmonary edema) So it’s a biochemical marker of Heart
Echocardiography :Utility of Echo failure/dysfunction (acute and chronic)
1.shows ALL the CARDIAC STRUCTURES (EXCEPT coronary arteries & Conduction pathway)
 Chambers: Size/dimension
Indication of Echo: To confirm:
 Valves: properly opening/closing
 Valvular diseases
 Septum: any defect  Septal defects
 Pericardium  Pericardial diseases
2.Assesses Cardiac functions‐ SYSTOLIC & DIASTOLIC function,  Cardiac failure
 so can detect ANY DYSFUNCTION  IHD
3.Can show any areas(s) having ISHCHAEMIA
 Ishaemic wall/area: Movement during contraction & relaxation will be
abnormal: Regional wall motion abnormality(also called Hypokinesia/Akinesia)
3.“Imaging” of electrical activity: Arrhythmia/ Ischaemia
 ECG‐ required WHENEVER Arrhythmia/ Ischaemia is suspected
 24 hours ECG: required WHENEVER Arrhythmia is suspected but ECG is inconclusive
4.Imaging of Coronary artery: ● Non invasive angio: CT/ MR angio ● Invasive Angiography
5.Tests which provokes ischaemia
These tests are indicated for patients whose clinical scenario is suspicious of Angina during stress/exertion.
In these tests myocardial ischemia is provoked by putting the heart under stress and simultaneously an
objective & near full-proof technique is employed to capture any ischemia.
(So as if the situation gets “RECREATED” in the lab)
Name of the test Method of provoking ischemia Method of capturing ischemia
Trade mill test: Walking on Trade mill machine Continuous ECG
Myocardial perfusion scan Physical stress: Physical exertion special scan of heart with a radiolabeled
Pharmacological stress: chemical- scan can capture areas not
Adenosine getting adequate perfusion( ischaemic
areas)
Dobutamine stress Pharmacological stress: Echocardiography
Echocardiography
Gastrointesinal (includes hepatobiliary)

1.Blood:
CBC/ CRP
Urea/Creatinine/Na/K
Intestinal (absorbs nutrients): Serum level of Albumin, Iron, Vitamin B12, Folate, Ca
Hepatobiliary:
Liver biochemistry: Bilirubin, SGOT, SGPT, Gamma GT. Alkaline Phosphatase
Synthetic function of Liver:
Albumin
Clotting protein: So clotting profile: PT/INR, APTT
Pancreatic: Amylase/ Lipase
2.Imaging: Radioimaging Endoscopy:
Xray abdomen Upper GI endoscopy
USG abdomen Lower GI endoscopy
CT abdomen
MRI abdomen
MRCP(MRI of pancreato‐biliary region)
3.“Regional” material”:
 Feces analysis: Stool Routine examination & Occult Blood test
 Ascitic fluid analysis
4.Biopsy: ● Radio imaging guided ● Endoscopic
Nephrological/Urological
1.Blood: CBC/CRP
Kidney functions Representative blood parameters
Renal biochemistry: In Kidney dysfunction
1. Toxin/Waste Elimination: Urea/Creatinine
 Urea/ Creatinine
2. Electrolyte balance: Na, K, Ca, Cl, PO4, Urate
 Electrolytes: Na, K , Ca, Cl,PO4
3. Acid‐base balance: ABG (H+, pH, HCO3)
 ABG: “acid‐ base gas”: pH, HCO3, H+ 4. Synthesis
 Biochemistry: Uric acid. Vitamin D Erythropoeitin: Hb
Prostate: PSA Active form of Vit D Vitamin D level
2. Imaging:
Radioimaging Endoscopy: Cystoscopy
Xray abdomen (KUB) CT abdomen (KUB)
USG abdomen (KUB) MRI abdomen (KUB)
3. “Regional” material”: Urine analysis
4. Biopsy: Biopsy: ● Radio imaging guided ● Endoscopic
Neurological
1. Blood: 4. “ECG” of the Nervous system
CBC/CRP/Blood C/S 1. Brain: EEG
Alteration of all of these
Ur/ Creat/Na/Glucose 2. Peripheral Nerves: NCV/NCS
can cause Encephalopathy
LFT/ABG/Calcium 3. Muscles: EMG
2. Imaging: Radioimaging: CT Brain/MRI Brain
Serves almost the same purpose as ECG does for the heart‐
3. “Regional” material”: CSF study these are tests which capture electrical impulses of the
respective areas & the electrical activity is represented on a
paper in graphical form
Hematological
Blood:
CBC: Hb,WBC, Platelet- Cytopenias‐ Mono/Bi/Pancytopenia or leukocytosis
(BUT remember!! Cytopenias may be due to a Non‐hematological disease)
typical blood picture of MANY hematological disease
Peripheral smear: Morphological abnormality of Blood corpuscles: “MOST VALUABLE” investigation
abnormality of RBC abnormality of WBC abnormality of Platelet

Gives an initial idea about Gives an initial idea about
Pattern of Anaemia Pattern of Leukaemia Cause of Thrombocytopenia
Pattern confirmation by
Iron parameters “Non marrow” causes to be ruled out
doesn’t fit
Hemolytic markers Bone marrow study: Biopsy/FNAC
with any
B12/Folate level
Cellularity Cell surface Markers Cytogenetic

Confirms many HEMATO LOGICAL diseases
1. Aplastic anaemia Each subtype of Leukemia 1. Each subtype of Leukemia
2. Leukemias (each has specific markers‐ 2. Myelodysplasia
3. Myelofibrosis different types of Cluster of (associated with specific gene
4. Myelodysplasia differentiation(CD) molecule) mutation/ deletion)
Management: Airway protection
A Indicated in following situations/patients
Airway protection 1. Respiratory: who needs to be ventilated
Admit 2. Patients at risk of NOT maintaining airway patency: ANY COMATOSE patient
Absolute bed rest Means of airway protection: Endotracheal intubation
Breathing support
B Indication: ANY patient with Hypoxia and/or Hypercapnoea (Respiratory patients)
Breathing support Means of breathing support: 1. Oxygen 2. Breathing machine (Ventilator & ECMO)
Bed sore prevention
Non invasive ventilation: By applying +ve pressure into the airways & alveoli creates a
Basic investigations
favourable environment for 02 & CO2 to flow in & out (“supports the patient to breath”)
Invasive/Mechanical ventilation: Intubated and then connected to the ventilatior through
C
the tube. The machine works by bringing O2 to the lungs and taking CO2 out of the lungs
Circulation
(“almost breathes for the patient”)
Catheter
However both types of may fail to maintain O2/CO2 balance if LUNGS are VERY BADLY
CBG monitoring
damaged (that’s when ECMO is required)
D
Diet 3. ExtraCorporeal Membrane Oxygenation: ECMO comes into play when there is “almost
Drug NO lungs”, so even Ventilator is failing. ECMO maintains tissue perfusion (so oxygenation)
DVT prophylaxis and removes/extracts CO2 from tissues WITHOUT any participation of Heart- lung. So
basically it’s a “HEART-LUNG” machine
E Bed sore (pressure ulcer) prevention

External intervention Indication: For ALL BEDBOUND (long/even if short term) patients
(Interventional treatment) Means of Bed sore prevention
 Non surgical 1. Frequent change of position- sidewise lying to avoid pressure on the back
2. Back care- to keep the back clean particularly if urinary/fecal soiling
 Surgery
3. Special mattress: air or water mattress
Exercise 4. Bed sore dressing to accelerate healing
 Physiotherapy
Circulatory support
F Indication: ANY patient whose “fluid needs” cannot be met by oral route, so
Follow up/Future planning MAINLY pts. with Hypovolemia irrespective of its types/cause
Means of circulatory support: 1. IV fluid 2. Blood transfusion
1. Principles of IV Fluid therapy:
Resuscitative amount= Initial BOLUS amount: for SOME: those significantly fluid
depleted most important MARKERS of which are hemodynamically unstable/low
urine output
Routine Maintenance amount: for ALL
2. Blood transfusion: for those with significant blood loss
Catheterisation
Indication:
Emergency: In acute retention
Elective: Many patients whom hourly urine output measurement becomes
important- hypovolemic patients
Diet
Following IMPORTANT decisions are often need to be considered depending on the clinical scenario
1. To give or not to give: To keep the patient NPM/NPO
 ALL patients with ongoing ACUTE abdominal pathology till “acuteness” settles
 ALL patients with significant DROWSINESS (at risk of aspiration)
 ALMOST ALL post-operative patients
2. Alternate route of feeding: To be considered if NPM state is to be continued for > 1-2 days
Tube feeding: (Enteral feeding but not through mouth)
 NG tube feeding ( Ryles tube): TEMPORARY solution: So usually when NPM state will be continued for
few days to few weeks
 Feeding Jejunostomy(FJ) tube or Percutaneous Endoscopic Gastrostomy(PEG) tube: LONG TERM
solution: So usually when NPM state will be continued for months to years
Total Parenteral Nutrition(TPN): Enteral Feeding not possible for a considerable period of time:
“Intravenous food”- Ready made Liquid with “calorie value”. This is Total Parenteral Nutrition (TPN)
TPN therefore is typically required for those who can neither have ORAL nor can be given TUBE feeding- so
basically delivery of food into the GI system is not feasible/ is contraindicated. SO nutrition is delivered
ENTERAL
3. Dietary modification: “Special” diet depending on the underlying disease/ condition
Summary:
IV FLUID is NOT a replacement of FOOD…….
IV fluid takes care of fluid & eletrolytes, it hardly has any calorie value, so any patient nutrion/calorie caome
from food. That’s why OFTEN we need think about dietary route when for any reason the patient is unable to
take/ it’s not feasible to give diet via “normal” (oral) route
DVT prophylaxis
Indication: ALL patients who will remain completely immobile for a while as immobility predisposes to
venous stasis in the lower limbs leading to DVT (which may in turn dislodge to cause Pulmonary embolism)
Means of DVT prevention:

1 .Leg stretching exercise
2. Compression stocking (Anti- DVT stocking)
3. Prophylactic Anticoagulation
4. Intermittent Pneumatic compression
Exercise
Indications: Patients with wide varieties of pathology benefits from exercise/physiotherapy
Extrenal intervention
Interventional treatment can be of 2 types:
1. Non surgical intervention: Placement/ insertion of a device/gadget into the body for THERAPEUTIC
purpose- eg. Stent/ Pacemaker machine/Endoscopic treatment
2. Surgical intervention
RESPIRATORY
Inspection & Palpation
Asymmetrical movement = movement restricted= underlying lung NOT expanding properly= hemithorax/ part of it
showing restricted movement is the ‘Pathological side’ however “pathology can be any 1 of these
Collapse/Fibrosis/Consolidation/Effusion/Pneumothorax
Shift: of Trachea & Apical impulse (casually called Mediastinal shift)
“Push”- shifted to opposite/contralateral side: Effusion/Pneumothorax
“Pull”- shifted to same/ipsilateral side: Collapse/Fibrosis
Shift occurs ONLY if underlying pathology is SIGNIFICANTLY “massive”- so often NO SHIFT in these situations
Percussion
Sound produced is due to air containing alveoli underneath
No sound= impaired/dull “More” sound= hyperresonant/tympanitic
No air: Collapse/Fibrosis/Consolidation Increased air content

Sound not getting ‘conducted’: Effusion/Thickened pleura Alveoli: Hyperinflation‐Emphysema
Pleura: Pneumothorax
Auscultation
Tracheo‐Bronchial breathing (”tubular“breathing) produces sound of air flowing back and forth through the tracheo‐
bronchial tree‐ because of the tubular structure of the bronchial tree, this sound contains a number of single frequencies
giving them a somewhat “musical” quality.
So‐called normal breath sound heard over the chest (coming through aerated lung), have a very “different quality”.
Firstly, air passing through progressively smaller bronchi and bronchioles results in the production of sounds
containing an increasing number of different frequencies, while the interposed alveoli with varying degrees of aeration
provide a vast quantity of tiny sound absorption units, so that sound arriving at the chest wall have lost much of their
musical character and volume.
So the sound “produced” changes its’ character (“Bronchial”) while passing through millions of aerated alveoli to
attain a different quality (“Vesicular”)
Breath sound abnormalities
Qualitative Quantitative
Bronchial breath sound over chest Vesicular breath sound- Intensity altered
Non aerated lung tissue Reduced/diminished VBS
Consolidation Air flow diminished= Air entry diminished
Collapse Complete 1. Partial non aeration: “Incomplete”Consolidation/Collapse/Fibrosis
Fibrosis 2. Airway resistance increased: COPD/Asthma
3. Non conducted surface: Effusion/Pneumothorax
In these situations Vocal resonance & Fremitus
Vocal resonance/Vocal Fremitus‐ increased Vocal resonance/Vocal Fremitus‐ diminished
Added sounds
Rhonchi/Wheeze= Airway NARROWING (Broncho”spasm”)
Airway remodelling “Physical” obstruction

COPD Tumor
Bilateral/scattered wheeze
Asthma Mucus plug Localized rhonchi
Foreign body
Crepts/Crackles:= Moist/wet alveoli (Moist sound)
Some form of FLUID inside alveoli
Secretion Exudate Hemorrhage Pulmonary edema
Bronchiectasis Pneumonitis Alveolar hemorrhage “squeezed out” “oozed out”

LVF ARDS
Chest findings (signs) of common diseases/conditions: “NO FINDINGS!!”- in EACH of these, chest examination
may be NORMAL if the underlying condition is minimal/ insignificant in “quantity/severity”
Condition Mediastinal shifting Percussion Breath sound VR/ VF Added sound(s)
Pleural  Often no shift at & below the level of effusion
effusion  Opposite: Dull VBS↓ ↓↓
massive effusion
Pneumothorax  Often no shift Entire hemithorax of the affected side

 Opposite: Tympanitic VBS↓↓ ↓↓ -
massive effusion
COPD No shift bilateral symmetrical

Hyperresonant Early stage
ONLY if Normal Normal Rhonchi- often
hyperinflated Well established case
VBS↓ ↓↓
Asthma No shift bilateral symmetrical
Normal Early stage/Inactive Rhonchi
Normal Normal
Active disease
VBS↓ ↓↓
Consolidation No shift Over that part of the chest wall which overlies the pathology
Normal Normal Crepts
Impaired: large VBS↓ ↓↓
consolidation Crepts
BBS ↑ Crepts
Collapse No shift Over that part of the chest wall which overlies the pathology
Normal VBS↓ ↓↓
Impaired: large
Same side BBS ↑
consolidation
Fibrosis Same side Over that part of the chest wall which overlies the pathology
Normal VBS↓ ↓↓ Crepts
Impaired: large
consolidation
CARDIOVASCULAR
Over view of CVS
S2
S1
Heart sounds
Normal heart sounds
S1: Atrioventricular valves closure – Mitral & Tricuspid S2: Semilunar valves closure ‐ Aortic & Pulmonary:
timing: at the end of diastole timing at the end of Systole
S3 & S4
**Genesis: You may become a cardiologist but will never become a cardio‐physicist, so don’t try to “understand” the genesis in details!!
S3 (also called Ventricular gallop) S4 (also called Atrial gallop)
Genesis: Rapid filling of dilated/noncompliant/overloaded ventricle during 1st rapid filling phase (EARLY diastole)
& last rapid filling phase (Atrial systole/LATE diastole) MAY create an unusual vibratory effect‐ this gets
transformed into a reverberation leading to production of these sounds
When the sound occurs during 1st rapid filling phase: it’s called S3
When the sound occurs during last rapid filling phase: it’s called S4
EARLY diastolic (just after S2) LATE diastolic (immediately before S1)
Clinical significance of S3 & S4: indicates Ventricular dysfunction however they DONOT appear till significant
dysfunction has occurred. So although S3 & S4 are considered to be a sign of heart failure but their absence
DOESNOT rule out heart failure.
At times, particularly in presence of tachycardia 3 sounds together (either S1+S2+S3 or S1+S2+S4) give rise to a
rhythm resembling that of a galloping horse‐ this is called Gallop rhythm
Murmurs: Turbulent flow of blood strong enough to produce audible noise
Streamline flow No murmur “power” of Turbulence enough to become “audible”
So turbulent flow present‐ BUT murmur NOT ALWAYS audible!!

(So, any “MURMUR producing condition” can be clinically “silent”)
Murmurs
NORMAL amount of blood flowing through ABNORMAL amount of blood flowing through
an ABNORMAL orifice/opening a NORMAL orifice/opening
Organic murmur Flow/ Innocent/ functional murmur

Systolic Diastolic Systolic Diastolic
MR/TR MS/TS MR/TR MS/TS
AS/PS AR/PR AS/PS AR/PR
VSD Recapitulate cardiac cycle!!!
MR/TR: Valves close at the end of diastole MR/TR leak/gap persists from the very beginning of systole LV/RV
to LA/RA backflow from the beginning of systole and continues throughout: PAN SYSTOLIC
AR/PR: Valves close at the end of systole AR/PR leak/gap persists from the very beginning of diastole Aorta/
Pulmonary artery to LV/RV backflow from the beginning of diastole but DOESNOT continue throughout the diastole as
pressure gradient between artery & Ventricle falls with progression of diastole: so EARLY DIASTOLIC
MS/TS: Valves open during diastole In MS/TS narrowing persists from the very beginning of diastole but early
diastole is Isovolumetric Relaxation, so valves are yet to open flow through narrowed orifice starts after
Isovolumetric Relaxation period: so MID DIASTOLIC
AS/PS: Valves open during systole In AS/PS narrowing persists from the very beginning of systole but early systole
is Isovolumetric Contraction, so valves are yet to open flow through narrowed orifice starts after Isovolumetric
Contraction period: so MID SYSTOLIC
VSD: LV RV shunt continues throughout the systole & diastole but diastolic pressure gradient being narrower,
turbulence is not enough to produce audible sound: so PAN SYSTOLIC
PDA: Aorta Pulmonary artery flow through PDA continues throughout the systole & diastole with significant
turbulence: so CONTINUOUS
Cardiac Drugs
Different classes of antihypertensive drugs:
1. ACE Inhibitors: Captopril/ Ramipril
2. ARB: Losartan/Telmesartan/Olmesartan
3. Aldosterone antagonist: Spironolactone/Eplerenone
4. Alpha Blockers: Prazocin/ Terazocin
5. Beta‐blocker: Metoprolol/ Carvedilol (α+β1 blocker)/Bisoprolol
6. Calcium channel blocker (CCB): Dihydropyridine: Cilnidipine/ Amlodipine/ Nifedipine
7. Centrally acting: Clonidine/ Alpha Methyldopa
8. Diuretics: 1. Thiazides: Bendroflumethiazide/ Chlorthialidone 2. Loop: Furosemide/Torsemide/ Bumetanide.
9. Dilator: Vasodilators: 1. Venodilator: Nitroglycerine/ GTN 2. Arteriolar dilator: Hydralazine
10. Direct Renin Inhibitor: Aliskiren( Rarely used)
Antiarrhythmics
Atrial(Supraventricular )Tachyarrhythmias Ventricular Tachyarrhythmias
Adenosine Amiodarone
Amiodarone Beta blocker
Beta blocker
CCB: Non DHPs‐ Verapamil/Diltiazem E for both tachyarrhythmias: Electrical cardioversion
Digoxin
Flecainide
Heart failure drugs

1. ACE Inhibitors: Captopril/ Ramipril 6. Diuretics: Furosemide/Torsemide/ Bumetanide.
2. ARB: Losartan/Telmesartan/Olmesartan 7. Dilator: Vasodilators:
3. Aldosterone antagonist: Spironolactone/Eplerenone Venodilator: Reduces preload: Nitroglycerine/ GTN.
4. β‐blocker: Metoprolol/ Carvedilol/Bisoprolol Arteriolar dilator: Reduces afterload: Hydralazine.
5. Contractility enhancing agent:
● Cardiogenic shock: Inotropes‐ Dobutamine/ Milrinone
● Digoxin: However, its role is very limited
Drugs used in IHD

1. Antiplatelet: Prevention of future thrombotic event
 Aspirin Atherosclerosis Risk factor modification:
 Clopidogrel/ Prasugrel/ Ticagrelor 1. Atorvastatin/ any other statins
2. Anticoagulant 2. Antihypertensive
 Low molecular weight heparin (LMWH) 3. Antidiabetic
 Fondaparinux
3. Beta blocker: Metoprolol/ Bisoprolol/ Carvedilol (Cardioprotective effect
4. Coronary artery dilators(Anti‐anginals): Nitrate/ Nicorandil/ Ranolazine
5. Clot “bursting” agents: Thrombolytics‐ Alteplase/Reteplae/Streptokinase
Valvular & Congenital Heart diseases: overview

Valvular defect Congenital Heart disease
Incomplete opening: Stenosis Congenital Valvular defect Nonvalvular defect

Incomplete closure: Incomptenece/Regurgitaton Septal Defects
PDA
Coarctation of aorta
Stenosis/ Regurgitaton may occur in Congenital Heart disease may be
Single valve Multiple valves 1.Valvular ONLY 2.Non valvular only 3.Combination of both
1 type of defect
Or both defects (Mixed valvular heart disease)
Any valve= Front or back door with respect to a CHAMBER
 Stenosis: FRONT door of a chamber is NARROW = fixed outflow obstruction with respect to that chamber
 Incompetence: BACK door of a chamber is LEAKY, so blood will backflow from that chamber to another
chamber for which that valve is actually the FRONT door
 Septal defect: Shunting of blood through the defect, so the chamber receiving that shunted blood has to deal
with Extra amount of blood
So in stenosis So in Incompetence & Septal defect:
A particular chamber
Chamber is having fixed outflow obstruction Chamber has to deal with Extra amount of blood
Pressure overload Volume overload
Dilatation/Hypertrophy
Dysfunction Arrhythmogenicity
Cardiac failure Tachyarrhythmias
Left heart Right heart Atrial origin Ventricular origin

MV disease: Left Atrial dysfunction TV disease Right Atrial dysfunction
AVdisease Left Ventricular dysfunction PV disease Right Ventricular dysfunction
Clinical manifestation
ANY Valvular/Congenital HD
Till Cardiac effects are not prominent Once Cardiac effects are significant Roughened valvular/
Septal Endocardium
Asymptomatic c/f of Heart failure and/or c/f of Arrhythmia Vegetations
LHF RHF c/f of Endocarditis
Breathlessness+/‐ Orthopnoea+/‐ PND Edema Blackout (syncope)
Cough Collapse Fever
Dizziness Galloping of heart (Palpitation)
Murmurs…see general discussion on Cardiac signs
Investigation of VHD/CHD (details in general discussion on Cardiac investigations…a quick recap!!)
ECG/24 hours Holter Blood C/S
Echocardiography Procalcitonin
Blood Pro BNP/NT‐Pro BNP/BNP level
CBC/CRP
Treatment of VHD/CHD
Supportive Definitive
Rx of Heart failure Rx of Arrhythmia Rx of Endocarditis Cardiac surgery
Valvular Heart disease Congenital HD
Valve replacement Correction of the defect
Prosthetic(artificial) valve technique

Made of
Bio(Tissue)Prostheis Metallic prosthesis Interventional Cardiological Surgical
Hemolytic diseases
Lots of DISEASES where HEMOLYSIS occurs
FOR EACH OF THESE Clinico- investigation picture shows
Evidence of Hemolysis & its effects “Unique” or “Special” effect
This is SAME for each of these diseases This is SPECIFIC of the particular diseases
Clinical manifestations of Hemolytic diseases: ≥ 1 of the followings:

A. Due to Anemia:
 Anemic look  Dizziness
 Breathlessness  Exercise intolerance
 Cardiac palpitation  Fatigue
B. Due to Breakdown (excessive hemolysis): Entire clinical picture depends on
 Icterus DEGREE of hemolysis.
 Splenomegaly (if spleen is the site of RBC destruction) Degree of hemolysis: In each disease
 Chollithiasis (Bilirubin pigment stone) DEGREE of hemolysis VARIES from
C. Due to Complication(s): person to person(with the same disease)
 Iron overload: Haemochromatosis: depending on the SEVERITY of the
 Heart‐ Cardiomyopathy: heart failure defect responsible for hemolysis.
 Iatrogenic complication (eg.: blood transfusion related)
D. Due to underlying Disease: Unique manifestation of that disease
E. Due to Extramedullary erythropoiesis:
 Liver: Hepatomegaly
 Spleen: Splenomegaly
 Bones: Skeletal changes
Investigation
A. Anemia: Hb: ↓
B. Breakdown (hemolysis): Site of hemolysis depending on the disease
 Unconjugated bilirubin: ↑ Indices Intravascular Extravascular
 LDH: ↑↑ particularly in intravascular hemolysis Hemoglobinuria + ‐
 Reticulocyte count: ↑ Hemosiderinuria + ‐
C. Complications detection: Haptoglobin ↓↓ ↓
 Iron overload: Serum iron ↑, serum ferritin ↑. Plasma free Hb ↑↑ N
 Blood borne infections: Tests for HIV, HBV, HCV
D. Disease confirmation: Special test- nature of which depends on the underlying disease
E. Extramedullry erythropoiesis: USG abdomen: often shows hepato‐splenomegaly
Treatment
1. Treatment of anemia: Packed cell transfusion Treatment of underlying disease (specific treatment)
2. Treatment of Iron overload: Iron chelators
3. Folic acid supplementation particularly in chronic hemolytic anaemia: Anemia may worsen if bone marrow fails to
compensate for accelerated hemolysis. This problem particularly happens if there is associated folate deficiency.
This event is therefore known as “aplastic crisis”.
Bleeding/ Hemostatic disorders
Hemostasis
Physiology: Local vasoconstriction Platelet adhesion+ aggregation Activation of coagulation cascade
(Intrinsic+Extrinsic & Common pathway activation)
Hemostatic diseases are therefore due to fault in either of these 3
Due to vessel wall defect Platelet defect Coagulation pathway defect
Rare Quantitative deficiency Qualitative defect Deficiency of Coagulation factors
So ignore!! Thrombocytopenia Defective Pl. function Reduced synthesis Overconsumption
Part of Pancytopenia Isolated thrombocytopenia Inherited diseases Acquired conditions

Most of the time (‘2 Ds’: Disease & Drug induced)
Bone marrow involving conditions Non‐ Marrow conditions
(‘2 Ds’: Disease & Drug induced) (‘2 Ds’: Disease & Drug induced)
Clinical features: of ANY bleeding disorder patient

Asymptomatic
Bleeding:
 Sites:
Circulatory compromise: hypotension/ tachycardia IF massive bleeding
Disease: Manifestation specific/ unique to the underlying disease: depends/varies according to the disease
Investigations
1. To confirm bleeding disorder:
 Platelet count
 BT: Mainly assesses the integrity of blood vessels, platelet aggregation and activation status
 CT: Roughly assesses the integrity of entire coagulation cascade
 PT, INR: Assesses the function of extrinsic pathway
 aPTT: Assesses the function of intrinsic pathway
 Thrombin time: Assesses the function of common pathway
2. To confirm the underlying disease: Special tests to diagnose the underlying disease.
Treatment of bleeding disorders
1. Treatment of bleeding manifestations:
 Antifibrinolytic:
o Tranexamic acid
o Aminocaproic acid
 Platelet transfusion
 Fresh frozen plasma
2. Specific treatment of the underlying disease
Malignancy
Solid tumor Liquid tumor

Organ/Soft tissue/bone/Lymph Node Hematological: Leukemias
Manifestations of ANY malignancy: May present with any of these 4 groups
Loco-regional effects Distant effects

1.Primary organ related manifestations 3.Metastatic: Common: Brain/Lymph node/Liver/bone/
Serous cavities
2.Surrounding organ related manifestations 4.Non‐ metastatic effects (Paraneoplastic syndrome)
(due to loco‐regional invasion/compression)
Investigations:
1. Suspicion: often from ABNORMAL Xray/USG/CT/MRI/Endoscopy of the primary/ metastatic site
2. To confirm malignancy
3. To confirm extent/burden of the disease (“Geography”)- this is the SINGLE MOST important parameter to
STAGE the disease for ANY MALIGNANCY: 1.Loco-regional extent 2. Distant spread
4. To assess overall physical fitness of the patient: Assessment of important organs
To confirm malignancy To know the spread Overall physical assessment
Cytology/Histopathology Radioimaging CBC
FNAC/Biopsy (also gives the 1st clue of the diagnosis) LFT
1.Radiologically guided Contrast CT‐ brain+ thorax + abdomen KFT
2. Endoscopic Contrast MRI‐ brain+ thorax + abdomen Ca
3. Surgical biopsy PET‐ CT whole body ECG
No guidance required for biopsy in Isotope bone scan‐ specially for Bone mets Echo
some cases like “Superfical” lesion PFT
which can be seen in naked eye
Treatment of Malignancy
depending on the scenario
Disease directed treatment Palliative treatment

(Symptoms/complication directed treatment)
Based on these Medical /Surgical therapy
1. Exact histopatholgical Type 4. Age
2. Stage of the malignancy 5. Financial factor
3. Comorbidities/Level of fitness 6. Response to any treatment already offered
Curative intention Disease downsizing/downgrading intention

(aim is to make disease free) (aim is to decrease disease burden)
Treatment options
● Surgery and/or ● Oncomedicine and/or ● Radiotherapy
Therefore for a particular malignancy TYPES of Surgey/ Oncomedicine/Radiotherapy: EACH can be with CURATIVE
or DOWNGRADING intention: ACCORDINGLY their NATURE/TYPE change
For almost ANY cancer the EXACT treatment strategy for a SAME malignancy differs from patient to patient & it may
be: 1.Any 1 of the above 2. Any 2 of the above 3. All 3 of the above
When SURGERY is the primary treatment
& ONCOMEDICINE and/or RADIATION is the “Helper”
Called Neoadjuvant therapy Called Adjuvant therapy

When delivered before the primary treatment When delivered after the primary
to help reduce the size of a tumor treatment to destroy remaining cancer
or destroy cancer cells that have metastasized. cells
Medical Oncology
Chemotherapy Targeted therapy Immunotherapy
Inhibits phases of cell cycle inhibits specific factor (“target molecule”) helps Immune system to fight
within malignant cell who are involved in better against malignancy by
proliferation/survival of cells augmenting immunological
reations
Leukemia
Key defect: Uncontrolled proliferation of WBCs
Starts at the level of stem cells (of WBC series)
Very rapid rate of proliferation in number & Not so rapid rate of proliferation in number, so
MOST of these cells cannot mature at all MOST of these cells get time to mature before
Released from marrow
“Spill over”from marrow before attaining maturation “Spill over” from marrow after attaining maturation
Proliferation + Maturation arrest Proliferation without maturation defect
Acute Leukemia Chronic Leukemia
Defect of: Myeloid series Lymphocytic series Defect of: Myeloid series Lymphocytic series
AML ALL CML CLL
However either of the Chronic leukemias can enter into an “accelerated” stage which is almost like getting
“TRANSFORMED” into an Acute leukemia
Mechanisms of clinical manifestations: (this more or less is applicable for any leukemia)
Bone marrow Infiltration: Normal marrow cellular population is replaced by Leukemic

cells leading to marrow failure
Symptoms & signs: Overall clinical manifestations can be ≥ 1 of the followings:
1. Due to bone marrow failure(infiltration): Any of these
Anaemia Neutropenia Thrombocytopenia
Asymptomatic Anemic look Asymptomatic Asymptomatic
Breathlessness Bacteteremia/ “Candida” i.e Fungemia: Bleeding manifestations:
Cardiac: palpitation  Fever and/ or Pattern: Spontaneous OR Refuses to
Dizziness  Focal manifestations of infection stop when it should
Exercise intolerance: reduced Site:
Fatigue ● Superﬁcial: Muco‐cutaneous
● Deep/ Internal bleeding
2. Due to organ infiltration:

 Hepatomegaly Abdominal discomfort/ dragging pain
 Splenomegaly +/- consequence of massive splenomegaly
 Lymphadenopathy Functional Gastric outlet obstruction: Post prandial Bloating
 Gum hypertrophy
 Meningeal signs (particularly in ALL)
3. Due to marrow expansion: Bone tenderness over sternum and pelvic region
4. Hypermetabolic/catabolic state:
 Constitutional symptoms: Fever, sweating, weight loss
 Hyperuricemia:
 Asymptomatic
 Acute gout
 Acute Kidney Injury( in case of “dangerous” hyperuricemia)
Common mode of presentation: Following 3
Anaemia +/‐ Organomegaly
1st clue of the disease: characteristic peripheral blood picture
Fever +/‐ focal manifestations of infection
Asymptomatic: particularly Chronic Leukemias
Investigations:
1. Blood picture: pattern depends on TYPE of leukemia
 Hb: ↓ or Normal depending on degree of marrow infiltration by leukemic cells
 Platelet count: ↓ or Normal
 WBC:
Acute leukemia/Accelerated stage of chronic Chronic Leukemia
Lots of immature cells of different generations particularly Leukocytosis with mostly mature cells
lots of circulating blast cells NO significant numbers of immature cells
WBC count: LOW as “count”= number of Mature cells CML: TC often > 50000 with PREDOMINANTLY
AML: Myeloblast/Promyelocyte/Metamyelocyte/Myelocyte Granulocytosis
ALL: abundant Lymphoblast CLL: TC often > 50000 with PREDOMINANTLY
Lymphocytosis
So, 1st clue of the disease is the characteristic blood picture, CLINICALLY it’s IMPOSSIBLE to say!!!
 Cell surface marker & Cytogenetic study: As leukemic cells are quite abundantly present in peripheral
Blood (“spill over” from marrow) so, LEUKEMIA specific cell surface markers & Cytogentic study can also be done on
peripheral blood sample
2. Bone marrow: FNAC/ Biopsy‐1.Cellularity 2.Immunohistochemistry/Immunophenotyping 3. Cytogenetics
a. Cellularity/Microscopic picture
Acute leukemia/Accelerated stage of chronic Chronic Leukemia
Cellularity: Plenty of blast cells: >20% blast cells Cellularity: Hypercellular; Blast cells: Usually <5%
in marrow is characteristic of an acute leukemic: CML: Myeloid hyperplasia
 Myeloblast in AML CLL: Lymphoid hyperplasia
 Lymphoblast in ALL Blast cells: 10‐20% = accelerated stage&> 20% blast crisis
b. Cell surface markers: Markers are SPECIFIC for each TYPE/LINEAGE. So identification of these markers
CONFIRMS the EXACT LINEAGE of leukemia
2 types of tests are there to identify these markers- utility same but the “technology” different
 Immunohistochemistry: can be done on“tissue”: so needs BM biopsy sample
 Immunophenotyping: can be done on “cellular fluid”: so needs BM aspiration sample
( So, Immunophenotyping can be done on blood sample PROVIDED abundant leukemic cells are present)
Common leukemia biomarkers are CD (cluster of differentiation) markers, a family of membrane proteins predominantly expressed
on the leukocyte surface- Expression of CDs varies according to the lineage of WBCs. So, CDs are cell surface markers which are
very useful for the identification and characterization of leukocytes and their different subpopulations.CD markers are mostly useful
for classifying WBCs and important for the diagnosis of Leukemias as well as Lymphomas.
SUMMARY: CDs are cell surface markers of different types of Leukemias
c. Cytogenetics: detects chromosomal/gene abnormalities which often is “ACUQIRED” by leukemic cell (eg.
Mutation/Translocation/deletion): Cytogenetic study mainly helps to diagnose & prognosticate the disease
Tests to detect complications/ overall assessment of patient:

1. LFT 3. Uric acid: ↑
2. RFT: Urea/Cr/Na/K 4. CSF: To look for meningeal infiltration
5. Septic screen: To find the focus of infection: ( in ALL particularly)
 Blood and urine: C/S ● CRP/ Procalcitonin ● Chest X Ray
Leukemia: Investigation summary

Blood investigation Bone marrow study
Peripheral blood picture Immunophenotyping Biopsy FNAC
Immunohistochemistry Immunophenotyping
+ Cytogenetic study
Treatment
Supportive treatment: Definitive treatment
Complication/Symptoms directed treatment Disease directed treatment
Supportive treatment: May require ≥ 1 of the followings
a. Treatment for Anemia: PRBC transfusion
b. Treatment for Thrombocytopenia: Platelet transfusion
c. Treatment for Neutropenia
 Reverse barrier nursing
 Febrile patient: Antibiotic: IV 3rd generation Cephalosporin/ Carbapenem + Teicoplanin
+/- Antifungal: Caspofungin/Voriconazole
 Granulocyte‐ Colony Stimulating Factor (G‐CSF): Filgrastim/Lenograstim
d. Treatment for Hyperuricemia: Hypouricemic drugs: Allopurinol/Febuxostat Uricosuric agent: Uriacse
Definitive treatment: Leukemias
Based on
1. Exact Type 4. Age
1. Medical BMT/Stem cell transplantation

within leukemic cells who are involved in better against malignancy
proliferation/survival of cells
Lymphoma
Malignancy originating in the lymphoid follicular cells with proliferation lymphoid follicular cells
Classification: 1. Hodgkin’s 2 Non-Hodgkin’s
Lymphoma
Proliferation of lymphoid tissue Extra-nodal organ infiltration Hypermetabolic state
Lymphadenopathy Liver: Hepatomegaly Constitutional symptoms Hyperuricemia

Spleen: Splenomegaly Fever Asymptomatic
Supeficial Deep (not palpable) Bone marrow: Bone marrow failure Sweating Acute Gout
Serous cavities: “effusion” Weight loss AKI
Palpable mass Compressive Effects
Clinical features: Overall clinical manifestations can be ≥ 1 of the followings:
1. Features of lymphadenopathy: typically presents with this
 Palpable lymph nodes: multiple regions involvement: Firm, non‐tender, discrete
 Mediastinal lymphadenopathy: May result in SVC obstruction/ Superior mediastinal syndrome
 Retroperitoneal lymophadenopathy: can cause Subacute intestinal obstruction
2. Features due to Extranodal spread:
 Hepato/spleno‐megaly
 Pleural effusion/ ascites
 Bone marrow failure at late stage: features of anemia and/or thrombocytopenia and/or Neutropenia
a) Constitutional symptoms: Fever, sweating, weight loss
b) Hyperuricemia:
 Asymptomatic
 Acute gout
 Acute Kidney Injury( in case of “dangerous” hyperuricemia
Investigations
1. Confirmation of diagnosis of lymphoma: Lymph Node biopsy: Ideally Excisional biopsy of a lymph node
If Excisional biopsy not feasible then Radiologically guided biopsy of the most accessible lymph node
Histopathological EXAMINATION: Confirms the type of Lymphoma
Lymphoma specific Cell surface marker : gives further subtypes
2. To assess the extent/spread of the disease: which is required for staging
o CECT of chest, abdomen and pelvis (to look for lymphadenopathy)
o Whole body PET CT scan
o Bone marrow: to look for bone marrow infiltration
3. Tests to detect complications/ overall assessment of patient:
1. CBC 5. Septic screen:
2. LFT  Blood and urine: C/S
3. KFT: Urea/Cr/Na/K  Chest X Ray
4. Uric acid: ↑  Procalcitonin
Treatment
Complication/Symptoms directed treatment Disease directed treatment
Supportive treatment: May require ≥ 1 of the followings

e. Treatment for Anemia: PRBC transfusion
f. Treatment for Thrombocytopenia: Platelet transfusion
g. Treatment for Neutropenia
h. Reverse barrier nursing
i. Febrile patient: Antibiotic: IV 3rd generation Cephalosporin/ Carbapenem + Teicoplanin
+/-
Antifungal: Caspofungin/Voriconazole
j. Granulocyte‐ Colony Stimulating Factor (G‐CSF): Filgrastim/Lenograstim
k. Treatment for Hyperuricemia: Hypouricemic drugs: Allopurinol/Febuxostat Uricosuric agent: Uriacse
Definitive treatment: LYMPHOMA

Based on
1. Exact Type 4. Age
1. Medical BMT/Stem cell transplantation Radiotherapy

within leukemic cells who are involved in better against malignancy
proliferation/survival of cells
Liver disease/dysfunction/ failure
Etiology/ disease/factor who can DAMAGE the liver
Persons with ANY of these etiologies
LIVER
In “pre-damage” state Beginning of liver damage
(“Healthy carrier”)
Depending on the etiology: pace of damage
Acute Liver disease Chronic liver disease
ALL of them Some of them Some of them

So, Liver disease DOES NOT automatically
mean it’s a cirrhotic liver!!!
Pre/Non cirrhotic stage Cirrhotic stage
Clinico‐investigation picture
Manifestation(s)/ Evidence(s) of liver damage Manifestation(s)/ Evidence(s) of liver damage

BUT ++
NO Evidence(s) of Portal Hypertension Evidence(s) of Portal Hypertension
Pathophysiology effects of hepatocellular damage/ disease/failure
• Derangement of synthetic function of liver: Albumin & clotting factor synthesis
• Derangement of metabolic function: Bilirubin metabolism
• Derangement of detoxifying function: detoxifies metabolically generated waste/toxin(portal vein delivers them
to liver)
• Derangement of hormone metabolism
• Derangement of synthesis and metabolism of endogenous vasoconstrictor and vasodilator
• Derangement of carbohydrate+ protein + fat metabolism
Clinical effects/manifestations of Liver disease: ≥ 1 of the followings (may be asymptomatic!!)
Anasarca: (hypoalbuminemia)
Bilirubinemia‐ Jaundice (deranged Bilirubin metabolism)
Coagulopathy(deranged clotting factor synthesis)‐ Asymptomatic OR Spontaneous bleeding
Disease‐ ANY unique/specific manifestation of the UNDERLYING Etiology‐ depends on the disease
Encephalopathy (Accumulation of toxic metabolic waste products due to deranged detoxifying function)
A. Altered sensorium D. Delirium, disturbed sleep rhythm (reversal of
B. Behavioral change (Indifference to others, sleep‐wake cycle), disturbed mood
childish behavior) E. Features of cerebral edema (due to ↑ICT)
C. Confusion, coma F. Flapping tremor
G. ↓GCS.
Fetor hepaticus
Glycemic
Hepato renal syndrome Derangement of synthesis and metabolism of endogenous vasoconstrictor and vasodilator
leads to an IMBALANCE which adversely affect Renal and Pulmonary Hemodynamics
Hepatopulmonary syndrome
Hyperestrogenemia: deranged metabolism of Testosterone & other Androgen leads to EXCESSIVE peripheral
conversion to Estrogen
1. Testicular atrophy 3. Gynecomastia
2. Loss of secondary sexual characters (sparse pubic and axillary hair) 4.
3. Spider nevus/ angioma
Hepatomegaly
Hypertension: Portal Hypertension ONLY when CIRRHOTIC stage develops
Portal Hypertension: ≥ 1 of the folllowings Pathophysiological clinical features
Ascites‐ Abdominal swelling changes
Elevated portal venous A Ascites
Bleeding varices: Hematemesis and/or Melena hydrostatic pressure
Collaterals‐ Visible over abdominal wall with direction of Opening up of portocaval B Bleeding varices GI
(Portosystemic) collaterals bleeding/ (at gastro-
filling “away from the umbilicus
esophageal junction)
Caput medusae: collateral at periumbilical region
C Collaterals- Venous
Congestive splenomegaly
prominence at
Disease related features superficial abdominal
Encephalopathy: Portosystemic encephalopathy wall with direction of
filling “away from the
Fetor hepaticus sweetish/ ammoniacal smell in the breath umbilicus”
due to presence of mercaptan Caput medusae - visible
collaterals surrounding
Gastropathy: non‐specific abdominal symptoms umbilicus
Hypersplenism: Splenomegaly with pancytopenia due to Portal venous congestion C Congestive
peripheral destruction of blood cells due to hyperactive  Splenic venous splenomegaly
reticuloendothelial congestion
[RE] cells of spleen D Disease- f/o underlying
disease responsible for
(may be asymptomatic!!) P. Htn
Toxic products bypass the E Brain: Encephalopathy-
liver and reach systemic Portocaval/ hepatic
circulation through encephalopathy
Portosystemic collateral
F Lung: Fetor hepaticus
Splanchnic congestion G Congestive gastropathy
Liver disease patients

Clinico-investigation picture

NO evidence of Portal Hypertension +++
evidence of Portal Hypertension
Investigations
1. Blood:
CBC, CRP
Na+ K+ Urea Creatinine
LFT: (detailed Discussion on LFT later)
Biochemical markers of HEPATO-BILIARY DISEASE: Bilirubin, Enzymes
Synthetic function markers: Bilirubin & liver enzymes tell us it’s a
Serum Albumin level DISEASED LIVER Albumin/clotting profile/
Coagulation profile: PT, INR (Extrinsic), aPTT (intrinsic) Ammonia tell us HOW BAD is the diseased liver
Detoxificating function marker: Serum Ammonia level
2. Imaging:
USG abdomen:
 Abnormal appearance of Liver or biliary tree helps helps to diagnose liver disease & it’s stage
 Biliary disease & it’s cause
 Shows many of the effects of Liver disease: Portal hypertension, ascites, Hepatosplenomegaly
CT/ MRI of Liver
MRCP: for biliary disease
3. Upper GI Endoscopy: MUST!! If Portal hypertension ( hence Cirrhosis) is suspected‐ to look for Varices
4. Liver biopsy/FNAC
Treatment of Hepatocellular failure

Supportive: Definitive:
Treatment of:
A. Ascites
B. Bleeding (or even non bleeding)varices
C. Coagulopathy
D. xx Etiology:Treat/ Remove
E. Encephalopathy End stage Liver failure: Liver transplantation
F. xx
G. Gastropathy
H. Hepato‐pulmonary/ hepato‐renal syndrome
Discussion on LFT
Bilirubin: Conjugated (Direct) & Uncojugated (indirect)
Between 2 fractions……
Proportionately both types Increased: Hepatocellular disease/dysfunction
Predominantly/Disproportionately Unconjugated Hyperbilirubinemia: Hepatocellular disease/dysfunction
OR Hemolytic disease
Predominantly/Disproportionately Conjugated Hyperbilirubinemia: Cholestatic (Intrahepatic/Extrahepatic)
disease/dysfunction
Liver enzymes:
 SGPT (AST)
 SGOT (ALT) (signifies hepatocellular inflammation/necrosis)
 GGT
 ALP (signifies cholestasis‐ intra/extrahepatic)
Hepatocellular disease/damage Cholestatic disease
Rise of SGOT/SGPT is typical Rise of ALP/GGT is typical

In many hepatocellular diseases there is often a In many cholestatic diseases there is often a
degree of intrahepatic cholestasis degree of intrahepatic inflammation
So ALP & GGT may rise So SGOT/SGPT may rise
So enzyme pattern may be

Hepatocellular disease/damage Cholestatic disease
1.High SGOP & SGPT only 1.High ALP & GGT only
2. High SGOT & SGPT + high ALP & GGT: 2. High ALP & GGT + high SGOT & SGPT:
Typically Degree of rise of SGPT / SGOT above their Typically Degree of rise of ALP and/or GGT above
normal upper limit is MORE than Degree of rise of GGT their normal upper limit is MORE than Degree of rise of
and/or ALP above their normal upper limit SGPT / SGOT above their normal upper limit
3.SGOT/SGPT- Normal or near Normal:
As SGOT/SGPT signifies hepatocellular inflammation
In hepatocellular diseases without significant
inflammation SGOT/SGPT may remain Normal/
minimally high
So Hepatitis/ steatohepatitis: SGOT/SGPT high
Cirrhosis: often SGOT/SGPT Normal
Synthetic function markers: Synthetic & Detoxifying functions are considered to be

Serum Albumin level “the most important” functions of the liver. So if they are
Coagulation profile: PT, INR (Extrinsic), aPTT (intrinsic) abnormal the liver is considered to be a failing liver.
If they are considered to be the prognostic indicator of the
Detoxifying function marker: Serum Ammonia level
liver disease
Bilirubin & liver enzymes tell us it’s a DISEASED LIVER Albumin/clotting profile/Ammonia tell us HOW BAD is the
diseased liver
Interpretation of LFT
Suspicion of Hepato‐biliary disease
Abnormal LFT (No suspicion-disease Asymptomatic+ No signs)

Pattern of Enzymes & Bilirubin: (BOTH to be seen before concluding)
Predominantly/Disproportionately Proportionately both types of

Conjugated Hyperbilirubinemia Hyperbilirubinemia
Degree of rise of ALP and/or GGT Degree of rise of SGOT and/or SGPT
above their normal upper limit is MORE than above their normal upper limit is MORE than
Degree of rise of SGOT and/or SGPT Degree of rise of ALP and/or GGT
above their normal upper limit above their normal upper limit
Biliary/Obstructive pattern/ disease Hepatocellular pattern/ disease

How serious is the patient
Albumin Low and/ or Clotting profile deranged and/ or Ammonia high
Liver failure: Reversible or Irreversible that depends on the particular scenario

Infection
Infection: Any Microorganism: Bacteria/Virus/Parasite/ Fungi
++ MULTI-ORGAN DYSFUNCTION/ FAILURE
SEPSIS
Processes Contributing To Specific Complications
AKI- due to Hypovolemia
ARDS- Non‐cardiogenic Pulmonary oedema by cytokines who increase pulmonary capillary permeability
Acidosis- Overproduction of Lactate due to tissue hypoperfusion (hypoperfusion is due to hypovolemia)
Bilirubin↑: Acute Liver injury(ALI)- by cytokines
Circulatory compromise (Shock)
 Inappropriate peripheral vasodilation by cytokines‐ fluid remains sequestered in peripheral circulation effective
volume decreases (due to this “invisible” loss)
 Increased capillary permeability by cytokines leakage of fluid into extravascular( interstitial) space effective volume
decreases(due to this “invisible” loss)
 Cardiac function compromised (but above 2 are the main causes of shock)
Cardiac compromise: Cytokine induced
DIC- release of procoagulant cytokines leads to a procoagulant state uncontrolled microthormbus generation this
overwhelms the capacity of coagulation factor synthesis Overconsumption of coagulation proteins Consumptive
Coagulopathy
Encephalopathy: Cytokine induced brain injury
SEPSIS related features

AKI: Oliguria/Anuria/Encephalopathy
ARDS: breathlessness/Hyopxic
Bilirubin: ALI: Jaundice/Encpehalopathy
Ciculation: Shock/Tachycardia/Low urine output
DIC: bleeding
Encpahlopathy
Infection
Microorganism: Bacteria/Virus/Parasite/ Fungi
Invasion: Through different routes
Systemic manifestations Focal manifestations: SYMPTOMS and/or SIGNS SEPSIS related features
Clinical clue they give (NOT present ALWAYS)
Clue: Infection/Inflammation going on Clue: Locality of the infection/inflammation
(“history” of the disease) (“geography” of the disease)
 Acute febrile illness
Name varies according to the Location
 Appetite loss
Lymph Node Gastrointestinal:
 Body weight loss
Lymphadenitis Enteritis
 Chill (+/‐ Rigor)
CNS Colitis
 Drowsiness
Meningitis Peritoneum: Peritonitis
 Energy loss
Encephalitis Hepatobiliary:
Infection ANYWHERE Ocular Hepatitis Cholangitis
Local/ focal manifestations Keratitis Genital
Pain Conjunctivits Vaginitis Balanopostitistis
Tenderness Ophthalmitis Cervicitis
Swelling & Redness (if the area is visible) Uveitis Salpingitis
Bleeding( not always) E: Pelvic inflammatory disease
Inflammatory Fluid/exudate Mastoiditis Urinary: UTI
 Accumulation Otitis Urethritis
 Secretion name of these change N: Sinusitis Cystitis
 Discharge according to the area T: Pharyngitis Tonsillitis Pyelonephritis
Collection leading to ABSCESS Cardiac: Skin & soft tissue
Endocarditis Cellulitis
Apart from these SYMPTOMS patients Pericardial: Pericarditis Folliculitis
May ALSO develop other SYMPTOMS & SIGNS Respiratory Carbuncle
pertinent to that organ/system Airway Furuncle
Tracheitis Bones
Laryngitis Osteomyelitis
Bronchitis Discitis (vertebral disc)
Now apply the “above” for Parenchymal Joints
each of the localities…..
Pneumonitis Synovitis
I expect you will NOT have
Pleural Septic arthritis
to read them while studying
the individual conditions
Pleurisy
Effusion Abscess can form in
ANY LOCALITY
SEPSIS related features

AKI: Oliguria/Anuria/Encephalopathy
ARDS: breathlessness/Hyopxic
Bilirubin: ALI: Jaundice/Encpehalopathy
Ciculation: Shock/Tachycardia/Low urine output
DIC: bleeding
Encpahlopathy
Investigations: Because infection can occur ANYWHERE, so for ANY system
these are relevant blood parameters…..
Infection by micro-organism (BACTERIA/VIRUS/FUNGI/PARASITE)
Inflammmatory response Microorganism in the bloodstream

HIGH “inflammatory markers” “Capturing” Microorganism
CBC:
WBC count Blood C/S (includes staining+ culture +drug Sensitivity if Culture +ve
CRP “Imprint” of Microorganism in blood: DNA/RNA/Antigen/Antibody
Procalcitonin
WBC & CRP PCT
High in Non-bacterial inflammation AS WELL Bacteria specific marker
“Regional” Materials
Brain: CSF
Utility of “regional material” tests
Respiratory: Sputum Infection/inflammation suspected:
Pleura: Pleural fluid  “regional material” tested for:
Cardiac: Pericardial fluid a. Inflammatory markers: WBC count/ Protein
GI: Feces b. Organism: stain/Culture/”Imprint”: DNA/RNA/Antigen/Antibody
Peritoneum: Ascitic fluid
Urinary: Urine
Genital: Swab SEPSIS related investigations
Abscess/Ulcer: Pus/ Discharge AKI: Urea/ Cr/Na/K Cardiac function: Echo
Joint: Synovial fluid ARDS: ABG/Chest Xray DIC: Clotting profile/Fibrinogen/FDP
ALI: LFT
Acidosis: ABG (Lactic acidosis)
Radioimaging: Overview in relation to DIAGNOSIS of infection

Radiographic Appearance of the suspected area
Abnormal appearance characteristic of a particular PATHOLOGY/DISEASE
Infective pathology: so radio-imaging appearance helps to diagnose

Further confirmation
1.”Regional” material: MICROBIOLOGICAL tests
2. Biopsy/FNAC: MICROBIOLOGICAL tests & Microscopic examination
[
Biopsy/ FNAC for infection
Most of the time their SUSPICION arises from CLINICO-RADIOLOGICAL information
Infective etiology
CONFIRMED BY following 2 tests of biopsy/FNAC sample

1.Microbiological tests 2.Histopathological examination
Histopathological examination: Even in infective etiology microscopic appearance of the tissue helps in diagnosis:
Plenty of neutrophil/Necrotic material/lymphocyte/ caseating granuloma
Antimicrobial
Broad spectrum Antibiotics
Beta lactams Aminogycosides Tetracycline “family” Quinolones
Penicillin/ derivatives  Amikacin  Tetracycline  Ofloxacin
Natrual Penicillins  Gentamicin Tetra derivative  Ciprofloxacin
 Pen V  Tobramycin  Doxycycline  Levofloxacin
 Pen G  Streptomycin  Minocycline  Moxifloxacin
Betalactamse resistant Tetra analogue
 Cloxacillin  Tigecycline
 Flucloxacillin
Aminopenicillin Anti MRSA agents
 Ampi/Amoxicillin Oxazolidinone
Carboxypenicillin 1st  Linezolid
 Ticarcillin Glycopeptide
Ureidopenicillin  Vancomycin
 Piperacillin  Teicoplanin
Cephalosporins 2nd Lipopeptide
 Daptomycin
Carbapenems
 Ertapenem Anti-anerobic agents
 Meropenem Nitroimidazole
3rd
 Metronidazole
 Imipenem
 Tinidazole
 Faropenem
 Ornidazole
Monobactam
 Aztreonam
4th Gram negative ONLY (poor
Beta lactam+ Beta lactamse Inhibitor activity against Gram +ves)
Amoxicillin+ Clavulanic acid Polymyxin
Piperacillin+ Tazobactam  Polymyxin B
Cefoperazone+ Sulbactam  Polymyxin E (Colistin)
Ceftazidime+ Avibactam Typically used in infection by
multiple drug‐resistant Gram
negative organism
Tuberculosis
Clinical features: 1. Systemic 2. Focal
Systemic: ≥ 1 of the followings
 Appetite loss  Chill (+/‐ Rigor)
 Acute febrile illness  Decreased
 Appetite loss  Energy loss
Focal: depends on the site of Infection
Active Pulmonary TB: severity of symptoms and signs depend on extent/degree of lung damage/involvement
Symptoms: Signs:
 Asymptomatic Signs of Consolidation
 Breathlessness Signs of Cavity
 Cough
 Chest pain
 Hemoptysis
Extrapulmonary TB: FEATURES VARY ACCORDING TO SITE/FOCUS
Pleural: 1. f/o Pl. effusion Lymph Nodes: Lymphadenopathy
Pericardial: 1. Superficial: typically palpable +/‐ tender node(s)
1. f/o Pericarditis 2. Deep lymph nodes: Mediastinal/hilar/intra
2. f/o Pericardial effusion abdominal enlarged node(s): mostly radiologically
Neurological evident
1. f/o Meningitis GU
2. f/o Tuberculoma 1. f/o PID
\
2. f/o urethritis/epididymitis/prostitis
Abdominal 3. Renal: Sterile pyuria( WBCs++ but no
1. f/o Colitis organism/culture negative)
2. f/o Intestinal obstruction (due to fibrotic stensosiis) Skeletal- Bone/Joint TB:
Peritoneal: Ascites 1. f/o Osteomyelitis
2. If vertebral: f/o compressive myelopathy
Adrenal: 1. f/o Adrenocortical insufficiency
Active pulmonary disease is NOT a prerequisite for an extrapulmonary TB
Investigations
1. Microbiological diagnosis: Confirmation of the disease‐
 Demonstration of AFB
 Mycobacterial Culture (preferably BACTEC MGIT)
 XpertTB/RIF assay: detects M. tb DNA + Rifampicin resistance( which is a predictor of INH resistance)
Samples for these tests are taken from the affected site/organ‐
Pulmonary TB- Extrapulmonary-
Sputum: spontaneous/induced Pleural‐ Pleural fluid/ Pleural biopsy
Bronchoscopic washing/lavage Meningeal TB‐ CSF
Lung biopsy Pericardial‐ Pericardial fluid
Lymph nodes‐ Biopsy
Peritoneal‐ Ascitic fluid/Peritoneal Biopsy
GU‐ urine/Vaginal swab
2. Supportive tests- they suggest TB when backed by proper clinical context
1. Radiological‐ Xray/CT findings 3. Biochemical marker‐ High ADA (Pleural fluid/Pericardial fluid/CSF)
2. Histopathological‐ Biopsy sample showing caseating granulomatous inflammatory changes
4. Mantoux test‐ DOES NOT confirm TB, SUGGESTS exposure to TB bacilli
HEMATO
Hematology
The disease behind CYTOPENIAS ( whichever “blood cell series” gets affected can be a Hematological disease OR a
non- Hematological disease
Features due to Anemia: ≥ 1 followings
A. Asymptomatic Anemic look
B. Breathlessness
“Content”of page 1 will be there in many haematological
C. Cardiac: palpitation diseases.....so often you will find only the “heading” while
D. Dizziness reading those diseases as it’s mentioned here as well as in
E. Exercise intolerance: reduced “General”notes
F. Fatigue
Features due to Neutropenia: ≥ 1 followings

A. Asymptomatic
B. Bacteteremia: Fever and/ or Focal manifestations of infection
C. “Candida” i.e Fungemia: Fever and/ or Focal manifestations of infection
Features due to thrombocytopenia: ≥ 1 followings

A. Asymptomatic
B. Bleeding:
 Sites:
Supportive treatment:
Treatment of anemia: Packed cell transfusion
Usual indications: 1.when patient is symptomatic due to anemia 2. Hb < 8 gm/dl 3. Significant blood loss
Treatment of thrombocytopenia: Platelet transfusion

Indication: 1. In case active bleeding
2.In absence of active bleeding platelet transfusion (also called prophylactic transfusion)
 platelet count less than 10000
 Before an invasive procedure which carries risk of bleeding
Treatment of Neutropenia: Neutropenia is defined as an Absolute Neutrophil Count (ANC) < 1500/μL:
 Reverse barrier nursing
 Febrile patient: Antibiotic: IV 3rd generation Cephalosporin/ Carbapenem + Teicoplanin
+/-Antifungal: Fluconazole/ Voriconazole/Caspofungin
 Septic screen: Investigate to find the organism & focus of infection
 Granulocyte- Colony Stimulating Factor (G-CSF): Filgrastim/Lenograstim
Anaemia
↓ RBC production ↑ RBC destruction

Iron deficiency anemia Hemolytic anemia Reticulocytosis
“No Reticulocytosis” B12/ Folate deficiency anemia
Aplastic anemia
Anameia of Chronic disease
Reticulocytes (immature RBCs) is a good indicator of bone marrow activity because it represents recent production
and is used to determine whether a production problem is contributing to the anemia
Iron deficiency anemia
Etiology
1.↓Iron intake: Nutritional deficiency
2.↓Iron absorption: Malabsorption: IBD, Coeliac disease, Whipple disease
3.↑Iron loss: Blood loss
 GI loss: Bleeding varices/Peptic ulcer disease/Parasitosis/IBD/Malignancy/Angiodysplasia/Hemorrhoids
 Menorrhagia
 Renal: hematuria GI blood loss can be OBVIOUS or OCCULT
 Respiratory: Hemoptysis/Alveolar Hemorrhage
 Trauma
 Intraoperative/post operative blood loss
Clinical features:
I Features due to Iron deficiency…(for “I’m a Final MB” types!!)
1. Spoon shaped nail: Koilonychia
2. Glossitis, cheilitis
3. Pica: Abnormal craving/ appetite for non-nutritive substances: ice, clay, chalk, soil, sand
D Features due to underlying Disease: Any evidence of bleed must be looked for; however, bleeding may be
occult particularly GI bleed
A Features due to Anemia: ≥ 1 followings
A. Asymptomatic Anemic look
Suspect Iron deficiency
B. Breathlessness
Any anaemic pt where the cause of Iron deficiency is NOT OBVIOUS
C. Cardiac: palpitation Because if it’s OBVIOUS you don’t have to “think”!!!
D. Dizziness
E. Exercise intolerance
F. Fatigue
Investigations
Blood:
1. FBC(CBC):
 Hb: ↓
 Peripheral film/smear: Microcyte, Hypochromia, Anisopoikilocytosis (variation in size and shape of RBC)
2. RBC indices: MCV:↓↓ (Normal in early stage of IDA and after acute bleed)
3. Serum iron studies:
 Serum iron: ↓ (may be normal in early stage of IDA)
 Serum ferritin: ↓ (but may be “falsely” normal or ↑ due to any co-existing inflammatory condition)
 Serum transferrin saturation: ↓
 Total iron binding capacity (TIBC): ↑
4. Other relevant investigation(s) to look for underlying disease(s): Any occult GI loss must be investigated:
I. Fecal occult blood test (FOBT)
II. GI endoscopy:
 Upper GI endoscopy
 Colonoscopy
5. Bone marrow: Low marrow Iron store ( but RARELY required as IDA is confirmed by above mentioned tests)
Treatment: 1. Symptomatic: Treatment of anemia 2. Definitive: Treatment of the underlying cause
1. Treatment of anemia:
1. Blood transfusion
2. Iron replacement therapy:
 Per oral: FeSO4 /Fe-gluconate: Usually continued for another 2-3 months even after normalization of hematological
parameters to replenish/build up body iron store adequately
 IV iron therapy:
Indications:
 Per oral iron intolerance
 Non-compliance to oral therapy
 Presence of malabsorption.
Dietary modifications: Iron rich diet: Green leafy vegetables/ Meat
2. Treatment of the underlying cause: depends on the cause
Differential diagnosis of microcytic anemia

1. Iron deficiency anemia
2. Thalassemia
3. Anemia of chronic disease (may be Normocytic as well)
4. Sideroblastic anemia
5. Lead poisoning
“Atypical” Hematological picture in IDA

 Iron deficiency but no anaemia= Low Iron/ Low Ferritin/ but Hb= normal= may occur in early stage of IDA
 IDA with Normal MCV- Hb low, Iron/Ferritin low but MCV Normal
1. Early stage of IDA 2. Immediately after an acute bleed
 IDA with Reticulocytosis- Brief period of Reticulocytosis occurs after Starting Iron replacement therapy
 Iron deficiency anaemia with High Ferritin: any co-existing inflammatory condition
Vitamin B12/ Folate deficiency anemia

Etiology of vitamin B12 deficiency
1↓Intake: Rare: strict vegetarians
2.↓Absorption
• ↓Intrinsic factor: a. Pernicious anemia b. Post gastrectomy
• Terminal ileal disease: Crohn's disease/Coeliac disease/Ileal resection
• Competition for B12: 1. Bacterial overgrowth 2. Fish tapeworm: [*Diphyllobothrium latum]
Etiology of folate deficiency
1.↓Intake: Alcoholism
2.↓Absorption: Intestinal mucosal disease: Crohn's disease/Ileal resection/Drugs: Phenytoin/Sulfasalazine
3.↑Demand: Pregnancy/Chronic hemolytic anemia
4. THFA reductase inhibitors: Methotrexate/Triamterene
Mechanism of clinical manifestations: In B12 or Folate deficiency, impaired DNA synthesis of hematological and
other rapidly proliferating cells occur, giving rise to following effects:
1. Hematological: RBC+ WBCs+ platelets: Cytoplasmic maturation continues normally, but nuclear maturation lags
behind; giving rise to Nucleocytoplasmic asynchrony. This leads to SHORTENED LIFESPAN & PREMATURE
destruction of all three series of blood cells, often leading to VARIABLE CYTOPENIAS. So often
PANCYTOPENIA occurs
2. GI: Mucosal cells damage
3. Neurological: Occurs ONLY in VitB12 deficiency & NOT IN Folate deficiency: Takes years to develop
Clinical features of vitamin B12 and folate deficiency anemia:
System Hematological Extra-hematological
CNS Gastrointestinal
Anemia Subacute combined Damage to rapidly proliferating GI
Mechanism degeneration (SACD) mucosal cells due to impaired DNA
synthesis
 Anemic look Degeneration of:  Diarrhoea
Clinical  Breathlessness  Pyramidal tract  Abdominal pain
features  Cardiac palpitation  Posterior column  Glossitis (Red beefy tongue)
 Dizziness  Peripheral nerves
 Exercise intolerance Higher function abnormalities
 Fatigue.
In folate deficiency, No NEURO MANIFESTATION only hematological and/or GI manifestations are present.
Pernicious anemia
Vitamin B12 deficiency anemia due to autoantibody mediated deficiency of intrinsic factor.
Pathogenesis:
 There is formation of autoantibodies against:
a. Gastric parietal cell: Causing decreased HCl secretion and atrophic gastritis
b. Intrinsic factor: Binds and neutralizes them.
 Eventually, there is deficiency of intrinsic factor and impaired absorption of vitamin B12.
Clinical features and Investigations: Same as vitamin B12 deficiency anemia.
Confirmation of diagnosis by: Anti-parietal cell antibody/Anti-intrinsic factor antibody.
Treatment: Lifelong vitamin B12 supplementation (usually IM route is preferred).
Investigations:
B12 or Folate def. can present with Anaemia ONLY or Variable cytopenia: Bi/ Pancytopenia
Blood:
1. CBC: variable cytopenia: All the 3 series may be affected: Hb: ↓/ TC: Normal/↓/ Platelet: Normal/↓
2. Peripheral film: RBC: Macrocytes: WBC: Hypersegmented neutrophils (4-6 lobes): Platelets: Abnormal morphology
3. RBC indices: MCV: ↑
4. Evidence of Mild hemolysis due to premature destruction of RBCs: LDH high/ Unconjugated Bili: high
5. Bone marrow: Erythroid hyperplasia + Megaloblasts
Mild hemolysis is not uncommon in B12/Folate deficiency
6. Estimation of serum vitamin B12/ folate level
7. Other relevant investigations to diagnose the underlying cause/ neurologic complications.
Treatment
1. Vitamin supplementation:
a. Vitamin B12: IM/Oral
b. Folate: Oral: Often both of them are administered together as combined deficiency is not uncommon.
2. Treatment of the underlying disease
Hemolytic anemia
Anemia characterized by accelerated destruction of RBCs.
Diseases causing hemolysis may be
1. Congenital or Acquired 2. Acute or chronic 3. Site of hemolysis: Extravascular ( Splenic) or Intravascular
Degree of hemolysis: For each disease DEGREE of hemolysis may vary from person to person depending on the
SEVERITY of the defect responsible for hemolysis
Clinical features of hemolytic anemia: ≥ 1 of the followings:

A. Due to Anemia:
B. Due to Breakdown (excessive hemolysis):
Entire clinical picture depends on DEGREE of
 Icterus hemolysis;
 Splenomegaly (if spleen is the site of RBC destruction) Degree of hemolysis: in each disease: May
C. Due to Complication(s): vary from person to person depending on the
 Iron overload: Haemochromatosis: SEVERITY of the defect responsible for
 Heart- Cardiomyopathy: heart failure hemolysis.
 Iatrogenic complication: blood transfusion related- blood borne infections
 Calculus cholecystitis (Bilirubin pigment stone)
D. Due to underlying Disease: Unique manifestation of that particular disease
In haemolytic diseases: Hyperbilirubinemia is often NOT
high enough to give clinical appreciable Jaundice
 Bones: Skeletal changes
Investigation
1. Evidence of anemia:
 Blood: Hb: ↓ Site of hemolysis
2. Evidence of excessive hemolysis: Indices Intravascular Extravascular
 Unconjugated bilirubin: ↑ Hemoglobinuria + -
 LDH: ↑↑ particularly in intravascular hemolysis Hemosiderinuria + -
 AST: ↑ Haptoglobin ↓↓ ↓
 Urinary urobilinogen: ↑ Plasma free Hb ↑↑ N
 Fecal stercobilinogen: ↑
3. Evidence of accelerated erythropoiesis:
 Reticulocyte count: ↑ Suspect haemolytic disease in these scenarios…
 Erythroid hyperplasia. 1. Anemia + Jaundice
4. Investigations to confirm underlying disease 2. Anemia + Jaundice + Organomegaly
5. Investigations to detect complications: 3. Anemia + Organomegaly
 Iron overload: Serum iron ↑, serum ferritin ↑. 4. Anameia but cause not obvious
 Blood borne infections: Tests for HIV, HBV, HCV 5. Jaundice only
Treatment 6. Jaundice + Organomegaly
1. Treatment of anemia: Packed cell transfusion DON’T suspect Hemolytic disease on the basis of
2. Treatment of Iron overload: Iron chelators “H/O repeated blood transfusion”!!!
3. Treatment of underlying disease (specific treatment) Remember- Thalassemia is NOT THE ONLY
haemolytic disease!!!
4. Treatment of complications
5. Folic acid supplementation particularly in chronic hemolytic anaemia: Anemia may worsen if bone marrow
fails to compensate for accelerated hemolysis. This problem particularly happens if there is associated folate
deficiency.
Hereditary spherocytosis (HS)
Congenital defect of RBC membrane protein resulting in accelerated destruction of RBCs in the spleen.
Pathophysiology:
Abnormality of RBC membrane protein: Spectrin/ actin RBCs loses deformibility as these proteins impart
scaffolding effect RBCs become spherical get trapped while passing through splenic pulp Accelerated
hemolysis
Clinical features:
Clinical features of hemolytic anemia:
A. Due to Anemia:
B. Due to Breakdown (excessive hemolysis):
 Icterus
 Splenomegaly (if spleen is the site of RBC destruction)
 Calculus cholecystitis
C. Due to Complication(s):
 Iron overload
 Iatrogenic complication (Ex.: blood borne infections).
D. Due to underlying Disease
Investigation
1. Blood: Hb: ↓
2. Peripheral blood film: Spherocytosis ++ but it is not diagnostic of hereditary spherocytosis
3. Reticulocyte count: ↑ (due to accelerated erythropoiesis) Reticulocytopenia suggests impending aplastic crisis.
4. Evidence of excessive hemolysis: Unconjugated bilirubin: ↑
5. To confirm hereditary spherocytosis:
 Osmotic fragility test: Spherocytes are vulnerable to get damaged by a hypotonic media.
 Coomb’s test: -ve ( +ve in autoimmune hemolytic anemia where there is spherocytosis + ↑osmotic fragility)
Treatment
1. Uninterrupted folic acid supplementation
2. Blood transfusion in case of significant anemia
3. Splenectomy in severe cases
Paroxysmal Nocturnal Hemoglobinuria (PNH)
Acquired stem cell disorder characterized by Pancytopenia+ Intravascular hemolysis + Prothrombotic state.
Pathogenesis:
Acquired defect of membrane proteins which play an important role in regulating membrane attack complex
Cells become vulnerable to complement mediated damage
Complement mediated lysis of RBC, WBC and platelet
Clinical manifestations: Clinical manifestations due to complement mediated lysis of RBCs:
1. Anemia….(ABCDEF)
2. Intravascular hemolysis: Hemoglobinuria: Dark/ cola colored urine: particularly occurs in the early morning as
nocturnal CO2 retention leads to acidification which facilitates hemolysis.
3. Leukopenia: Increased risk of infection
4. Thrombocytopenia Asymptomatic or Bleeding manifestations
5. Complement mediated clumping of platelet: Prothrombotic state : unprovoked DVT
Investigations
1. Blood: CBC
 Hb: ↓
 TC: ↓
 Platelet count: ↓
2. Evidence of hemolysis:
 Unconjugated bilirubin: ↑
 LDH: ↑
3. Evidence of intravascular hemolysis:
 Urine Hb: ↑↑
 Urine hemosiderin: ↑
 Haptoglobin: ↓↓
4. Confirmation of diagnosis of PNH: Flow cytometry detects abnormal proteins: CD55, CD59
Treatment
1. Anemia: Blood transfusion
2. Prevention of venous thrombosis: Anticoagulants
3. Specific Rx
 Eculizumab: approved for treatment of PNH
 Corticosteroid
G6PD Deficiency
Hemolytic anemia precipitated by oxidative stress in G6PD deficient individuals.
Pathogenesis:
G6PD deficiency ↓ Glutathione (which plays a major role in preventing oxidative damage of RBC) Oxidative
stress Denaturation of Hb forming a precipitate within RBC (Heinz body) These RBCs while passing through
spleen gets trapped and destroyed
Clinical features:
Oxidative stress induced acute intermittent hemolysis:
 Anemia
 Icterus
Often the oxidative stress is drug induced: Primaquine/Nitrofurantoin/ Sulfonamides
Investigations: Investigations are abnormal during active hemolytic spells:
1. Hb: ↓
2. Peripheral film:
 Heinz body
 Bite cells: Pitted RBCs looks like they have had a bite taken out of it
3. Evidence of hemolysis: Unconjugated bilirubin: ↑/ LDH: ↑/ Reticulocyte count: ↑
3. Confirmation of diagnosis: Estimation of G6PD: Ideally should be confirmed after couple of weeks of active
hemolytic spells as fresh cohort of RBCs (young RBCs) present during hemolysis may contain adequate amount of
G6PD giving a normal result.
Treatment: Avoid offending drugs.
Sickle cell disease
Qualitative hemoglobinopathy characterized by abnormal shaped RBCs which are prone to get destroyed and
clumped.
Pathogenesis:
Clinical features:
1. Vaso-occlusive spells (particularly affecting veins):
Organ involved Clinical features
Brain Venous sinus occlusion
Lung Pulmonary artery clot-> Acute chest syndrome
Bones Ischemic necrosis (severe bony pain)
Osteomyelitis (Salmonella is the commonest organism)
Spleen Splenic infarct causing acute LUQ pain: Repeated episodes leads to autosplenectomy
a. Anemia
b. Icterus
c. Spleen: May be palpable in children, not palpable in adult due to hyposplenism.
Tendency of sickling is aggravated by: 1. Dehydration 2. Hypoxia 3. Acidosis
Investigation
1. Hb: ↓
2. Peripheral blood film:
a. Howell Jolly bodies: Due to hyposplenism, nuclear remnant of RBCs seen
b. Sickle cells.
3. Evidence of accelerated hemolysis:
a. Unconjugated bilirubin: ↑
b. LDH: ↑
a. Reticulocyte count: ↑: A normal reticulocyte count indicates an impending episode of aplastic crisis.
5. Confirmation of diagnosis: Hb electrophoresis confirms the diagnosis: shows HbS.
Treatment
1. Treatment of vaso-occlusive spells:
 Proper hydration  Analgesics to reduce pain
 Oxygen in hypoxia  Exchange transfusion
 Treat infections by antibiotics
2. Definitive treatment:
 Curative: Bone marrow/ stem cell transplantation
 Hydroxyurea: Decreases tendency of sickling by increasing circulatory HbF levels.
Thalassemia
Quantitative defect in Hb synthesis leads to chronic hemolytic anemia.
1. α-thalassemia:
If α-chain deficiency is significant, β-chain gets precipitated forming a tetramer within the RBCs. These RBCs
get destroyed by the spleen.
2. β-thalassemia:
α-chain synthesis goes on but proportion of α2β2 (HbA) gets reduced. Excess α-chain leads to 3 abnormalities:
a. Precipitation within RBCs: RBCs undergo hemolysis
b. Increased α2δ2 (HbA2)
c. Increased α2γ2 (HbF).
Clinical features of thalassemia:
A.Due to Anemia:
B.Due to Breakdown (excessive hemolysis):
 Icterus
 Splenomegaly (if spleen is the site of RBC destruction)
 Calculus cholecystitis
C.Due to Complication(s):
 Iron overload
 Iatrogenic complication (Ex.: blood borne infections).
D.Due to underlying Disease
D.Due to Extramedullary erythropoiesis:
 Bones: Skeletal changes: frontal bossing/ depressed bridge of the nose/parietal eminence (“Thalassemia
face”)
Investigations
a. Hb: ↓
b. TC, DC, CRP: Normal
c. Peripheral blood smear: Microcytic anemia (microcytosis is out of proportion to the degree of anemia)
d. MCV: ↓ often disproportionately low
e. Iron studies: if significant iron overloading
 Serum iron: ↑
 Serum ferritin: ↑
 Unconjugated bilirubin: ↑
 LDH: ↑
a. Reticulocyte count: ↑
b. Bone marrow: Erythroid hyperplasia
c. Skull X Ray: Hair on end appearance.
4. Evidence of iron overload:
a. Serum iron/ serum ferritin: ↑
b. Echocardiogram: To assess cardiac function
c. MRI heart.
5. Detection of iatrogenic complication: Viral serology (for HIV/ Hep C/Hep B)
6. Confirmation of diagnosis of thalassemia: Hb electrophoresis.
Treatment
1. Supportive treatment:
Packed cell transfusion (the frequency of which depends upon severity of symptoms and level of Hb in blood):
2. Prevent and treat iron overload: Injectable agent: Desferrioxamine Oral agent: Deferiprone
3. Treatment of complications: Treatment of cardiomyopathy
4. Definitive/ curative treatments:
 Bone marrow transplantation
 Splenectomy: As it is the main site of RBC destruction.
 (“Final MB type” topic!!...specially in Paed. Med )
Supertransfusion: blood transfusion strategy is timed in such a way that Hb > 12 gm % is maintained
Hypertransfusion: blood transfusion strategy is timed in such a way that Hb > 8 gm % is maintained
Saline washed RBC: Washed red blood cells which have had most of the plasma, platelets and white blood cells removed
and replaced with saline or another type of preservation solution. This helps to prevent the recurrence of severe allergic
transfusion reactions usual cause of which is proteins in the donor plasma. These proteins are removed by the process of
washing the red blood cells.
Neocyte transfusion.: Transfusional iron overload leading to cardiomyopathy can be a major problem in chronically
transfused patients. Young red cells (neocytes) survive longer after transfusion and therefore may contribute to the
extension of the intervals between transfusions
Differential diagnosis
1. Other causes of chronic hemolytic anemia:
a. Hereditary spherocytosis
b. Sickle cell anemia.
2. Other causes of microcytic anemia:
a. Iron deficiency anemia
b. Anemia of chronic inflammation
c. Sideroblastic anemia
d. Lead poisoning.
3. Other causes of predominantly unconjugated hyperbilirubinemia:
a. Hemolytic diseases
b. Inherited liver diseases:
 Bilirubin canot Go: Gilbert syndrome
 Bilirubin cannot Conjugate: Crigler-Najjar syndrome
(Cojugated hyperbilirubinemia: Bilirubin cannot depart: Dubin-Johnson syndrome/ Rotor syndrome.
RDW (Red cell distribution width): measure of degree of variation of RBC size.
 Normal value: 11.5%-14.5%
 Abnormality:
RDW MCV Interpretation
↑ ↓ Iron deficiency anemia
↑ N Acute hemorrhage
↑ ↑ B12/ Folate deficiency
N ↓ Thalassemia/ other causes of chronic hemolytic anemia
Types of thalassemia according to clinical scenario:
Minor Intermediate Major
Asymptomatic, with only abnormal Symptomatic, clinical impact of Symptomatic, significant clinical impact
hematological parameters disease not significant
Does not require blood transfusion Requires occasional blood Transfusion dependent
transfusion
α-thalassemia
Genes Hematocrit MCV Comment
deleted (Normal: 45-55%) (Normal: 85-105)
1 Normal Normal Silent carrier
2 30-40% 60-75 α-thalassemia trait
3 20-30% 60-70 Hemoglobin H disease
4 - - Hydrops fetalis
β-thalassemia
Type HbA HbA2 HbF
(Normal: 95-96%) (Normal: 1-3%) (Normal: <1%)
Minor 85-95% 4-5% 1-5%
Intermediate 0-30% 1-10% 0-100%
Major 0-10% 4-10% 95-96%
Autoimmune hemolytic anemia (AIHA)
Hemolysis of autoantibody coated RBCs.
Causes/ types:
AIHA
IgG antibody coated RBCs IgM antibody coated RBCs
These RBCs are destroyed at a temperature of 37⁰C, These RBCs are destroyed at a relatively low temperature,
which is almost equal to normal body temperature therefore often no hemolysis occurs in normal body
temperature
So, these are called "Warm antibody" So, these are called "Cold antibody"
Causes: Causes: Mycoplasma infection
1. Idiopathic
2. Drugs (Penicillin/ cephalosporin)
3. CLL
4. Some patients of ITP
Clinical features:
1. In many persons, it is completely asymptomatic
2. In case of chronic hemolysis:
a. Anemia + symptoms due to anemia
b. Jaundice
c. Splenomegaly
3.Features due to the underlying disease.
Investigations
a. Hb: ↓
b. Presence of Spherocytes
a. Unconjugated bilirubin: ↑
b. LDH: ↑
a. Reticulocyte count: ↑
b. Bone marrow: Erythroid hyperplasia
4. Coomb’s test:
a. Direct: Usually +Ve (detects antibody coated RBCs)
b. Indirect: May/ may not be +Ve (detects free antibody in serum).
Treatment
1. None required in case of insignificant hemolysis
2. In case of significant hemolysis:
a. Prednisolone
b. Splenectomy
Microangiopathic hemolytic anemia (MAHA)
Accelerated intravascular hemolysis due to damaged microvasculature wall.
2 disease belong to this family:
1. Thrombotic thrombocytopenic purpura (TTP)
2. Hemolytic uremic syndrome (HUS).
Thrombotic thrombocytopenic purpura (TTP)
Pathogenesis:
Triggering factor(s)
Increased activity of vWF (due to deficiency of vWF cleaving protease)
↑ Platelet adhesion and aggregation
Microvascular thrombosis (composed of plalelet + fibrin): Microangiopathy
Frictional damage of RBCs Ischemic organ damage (Cerebral >> Renal) Consumption of platelets: used up in
while passing through these vessels microvasculature thrombus formation
Intravascular hemolysis Thrombocytopenia
Clinical features:
T Features due to thrombosis CNS thrombosis:
 Seizure
 Confusion
 Delirium
 Encephalopathy
 Fluctuating focal neurological signs.
T Features due to thrombocytopenia Bleeding manifestations:
Superficial:
 Purpura
 Gum bleeding
 Epistaxis
Internal bleeding:
 Gastrointestinal,
 Genitourinary,
 Intracranial.
P Premature destruction of RBC ( hemolysis) Pallor + Jaundice
Investigation
1. Blood:
 Hb: ↓
 Peripheral film: Fragmented RBCs (Schistocytes)
 TC: Normal
 Platelet count: ↓
 Unconjugated bilirubin: ↑
 LDH: ↑
 Hemoglobinuria
 Hemosiderinuria
 Serum Haptoglobin: ↓.
Treatment: Supportive (Plasmapheresis).
Hemolytic uremic syndrome (HUS)
Pathogenesis:
Triggering factor(s): (Bloody dysentery caused by Shigella/ E.coli O157)
Increased activity of Platelet aggregating factor

↑ Platelet adhesion and aggregation
Microvascular thrombosis (composed of plalelet + fibrin): Microangiopathy
Frictional damage of RBCs Ischemic organ damage (Renal >>cerebral) Consumption of platelets: used up in
while passing through these vessels microvasculature thrombus formation
Intravascular hemolysis Thrombocytopenia
Clinical features:
1. H/O bloody diarrhea is usually present
2. Features due to thrombotic damage to kidney:
3. Features due to thrombocytopenia:
Bleeding manifestations:
Purpura, gum bleeding, epistaxis, internal bleeding (GI/ GU/ IC).
4. Pallor (mild) ± Jaundice (mild).
Investigations
1. Blood:
 Hb: ↓
 Peripheral film: Fragmented RBCs (Schistocytes)
 Platelet count: ↓
 LDH: ↑
 Hemoglobinuria
 Hemosiderinuria
 Serum haptoglobin: ↓
4. Renal function:
Urea Creatinine: ↑ (in case of uremic encephalopathy)
Serum K+: ↑
5. Stool culture and sensitivity.
Treatment
Primarily supportive:
1. In case of acute kidney injury: Dialysis
2. In case of severe hemolysis: Plasmapheresis.
Pancytopenia
Reduction in all 3 series of blood cells.
Causes:
“Central” causes= Bone marrow diseases Peripheral causes= excessive peripheral destruction
1.Marrow failure: Aplastic anaemia Hypersplenism
2. Marrow infiltration PNH
Hematological malignancy Severe Sepsis
 Acute Leukemias
 Accelereated stage of Chronic Leukemias
 Multiple Myeloma
 Lymphoma
Non- Hematological Malignancy
 Marrow Metastasis
3.Marrow fibrosis: Myelofibrosis
4. Marrow dysoplasia: Myelodysplastic syndrome
5. B12/Folate deficiency *(Marrow “poor” in raw material)
Clinical features of pancytopenia: Patient may be completely Asymptomatic
1.Features due to anemia:
Asymptomatic Cardiac palpitations
Anemia Dizziness
Anaemic look Exercise intolerance
Breathlessness Fatigue
2.Features due to thrombocytopenia:
Asymptomatic
Bleeding: spontaneous or prolonged bleeding after minor injury
Superficial: Purpura/ Gum bleeding/ EpistaxisDeep/Internal hemorrhage: GI/ GU/ ICH/Hemarthrosis
3.Features due to neutropenia: Increased risk of infections:
Asymptomatic In many of the “Pancytopenia causing” diseases
Bacteremia/ Fungal infections: Fever +/- focal manifestations Organomegaly occurs
4.Features due to the underlying disease: any specific manifestations of the underlying cause
Investigations: Finding the underlying disease is the main aim
1. Blood:
a. Full blood count
b. Peripheral film/smear: Abnormal in many of the underlying diseases with characteristic abnormality
c. Evidence of hemolysis: LDH/ Unconjugated Bilirubin (PNH causes Hemolysis)To look for abnormal/ immature
cells
d. RBC indices: MCV- may be ↑ if B12/Folate deficiency is the causes
2. Blood level of Vitamin B12/ Folate
3. USG:Liver and spleen size
4. Bone marrow: OFTEN required to confirm the marrow disease
Histopatholgy( cellularity) + Immunohistochemistry+ Cytogentic study
5. Any other special tests to confirm the diagnosis.
Treatment of pancytopenia
1.Supportive treatment: 2. Definitive treatment: depends on the disease
a. Treatment of anemia:Packed cell transfusion
b. Treatment of thrombocytopenia
c. Treatment of neutropenia
Aplastic anemia
Bone marrow hypocellularity leading to pancytopenia in the absence of marrow infiltration and fibrosis.
Causes:
Idiopathic: Immunologically mediated
Iatrogenic: drugs may potentially cause aplastic anemia
 Anticancer drugs
 Antibiotics: Chloramphenicol/ Sulfonamide
Infections:
 HIV
 HBV
Clinical features:
1. Features of anemia
2. Features of thrombocytopenia
3. Features of neutropenia
4. Absence of hepatosplenomegaly
Investigation
1. Blood:
a. Hb: ↓
b. RBC count, WBC count, Platelet count: ↓
c. RBC indices: MCV: Normal.
2. Serum vitamin B12 and folate level:To rule out deficiency.
3. Unconjugated bilirubin and serum LDH:To rule out hemolysis.
4. Viral serology (HIV, HBV):To rule out infections.
5. USG abdomen:To look for organomegaly.
6. Bone marrow examination: Biopsy detects hypocellular marrow.
Treatment
Aplastic anaemia
Supportive treatment Definitive treatment

Treatment of Anemia Treat/reverse any treatable factor
Treatment of Neutropenia Idiopathic AA
Treatment of thrombocytopenia
<50 years > 50 years
<35 years 35-50 years:

depending
on the scenario
HSCT Medical management
Hemopoeitic stem cell transplantation (HSCT) 1 line: AntiThymocyte Globulin (ATG)+ Cyclosporin
st
Donor stem cell transplantation 2nd line: used for disease refractory to 1st line
Ideal donor: HLA matched sibling ▪Alemtuzumab
Alternative donor ▪Eltrombopag
 HLA matched family member
 HLA matched unrelated donor
Anemia of chronic inflammation ( not a “must read” topic!!)
Causes:
1. Rheumatoid arthritis
2. Inflammatory bowel disease
3. Chronic kidney disease.
Pathogenesis:
It is a multifactorial disorder:
1. Ineffective usage of Iron in erythropeisis: due to abnormal activity of Hepcidin which is an iron regulatory protein
2. Decreased responsiveness of erythropoietin to its receptors
3. Decreased erythropoietin synthesis (particularly occurs in CKD)
Clinical features:
1. Mild to moderate anemia
2. Features of underlying disease
Investigations
1. Blood:
 Hb: ↓
 MCV: often Normal but may be ↓
2. Iron studies:
 Serum iron: Normal
 Serum ferritin: Normal/ ↑
Differentiating 3 common anemia from iron studies:
Parameters IDA Thalassemia Chr. Inflam.
MCV ↓ ↓ N/↓
Serum Fe ↓ ↑ N/↓
Serum Ferritin ↓ ↑ N/↑
Treatment
2. Packed cell transfusion (when anemia is symptomatic)
3. Regular erythropoietin supplementation (particularly in CKD)
Sideroblastic anemia: ( not a “must read” topic!!)
Anemia resulting from defective haem synthesis/ metabolism.
Pathophysiology: Defective haem synthesis ultimately leads to ineffective erythropoiesis; causing anemia.
Causes:
1. Idiopathic 3. Drug: Isoniazid
2. Chronic alcohol use 4. Chronic infection/ inflammation.
Clinical features:
1. Asymptomatic
2. Symptomatic due to anemia.
Investigations
1. Blood: Hb: ↓WBC/ Platelet: Normal
2. Peripheral film: Microcytic anemia with Dimorphic picture (Small + normal sized RBCs)
 If caused by chronic alcohol use, there is macrocytic anemia.
3. Serum iron studies:Picture of iron overload (due to defect in iron metabolism):
 Serum iron: ↑/Transferrin saturation: ↑/Serum ferritin: May be ↑
4. Bone marrow: Shows ring sideroblast (iron gets deposited within abnormal nucleated RBCs encircling the
nucleus).
Treatment Supportive: Blood/ packed cell transfusion.
Bleeding disorders
Etiology of bleeding disorders:
As part of pancytopenia
 Bone marrow disorders
 Non-bone marrow disorders
Isolated thrombocytopenia
 Immune mediated (ITP)
 Infection Dengue/HIV
 Iatrogenic: Heparin induced (HIT)
Clinical features:
Thrombocytopenia/Coagulopathy: ≥ 1 of these
Asymptomatic
Bleeding:
 Sites:
C: Circulatory compromise: hypotension/ tachycardia IF massive bleeding
D: Disease: underlying disease related manifestation: depends/varies according to the disease
Investigations
1. Clotting profile:
 Platelet count  PT, INR: Assess the function of extrinsic pathway
 BT: Mainly assess the integrity of blood vessels,  aPTT: Assess the function of intrinsic pathway
platelet aggregation and activation status  Thrombin time.
 CT: Roughly assess the overall integrity of
coagulation cascade/pathway
2. Special tests to diagnose the underlying disease.
Treatment of bleeding disorders
1. Supportive: for bleeding manifestations: 2.Definitive treatment of the underlying disease
 Antifibrinolytic:Tranexamic acid/ Aminocaproic acid
 Platelet transfusion- for thrombocytopenics
 Fresh frozen plasma- for Coagulopathics
Hematoma
Collection of blood underneath the skin.
Types:
Purpura
Reddish discoloration of skin due to bleeding underneath the skin.
Causes:
1. Purpura + Thrombocytopenia: therefore called Thrombocytopenic purpura
a. Part of pancytopenia
b. Isolated thrombocytopenia.
2. Purpura (without thrombocytopenia): therefore called Non- Thrombocytopenic purpura
a. Vessel wall disorder:
I. Age related
II. Vasculitis
III. Scurvy
b. Defective platelet function: von Willebrand’s disease (vWD)
c. Coagulopathy.
Clinical manifestations:
1. Due to thrombocytopenia: Spontaneous bleeding
2. Purpura: Reddish, non-blanching spots; palpable (vasculitis)/ non-palpable (non-inflammatory cause)
3. Features of the underlying disease.
Investigations:
1. Clotting profile
2. Investigations to detect the underlying disease.
Idiopathic thrombocytopenic purpura (ITP)
Disease characterized by immune autoantibody mediated thrombocytopenia.
Types:
ITP is of 2 types: Acute ITP: Usually occurs in newborns/ children Chronic ITP: Usually occurs in adults.
Pathophysiology:
Viral infection Antibody formation against platelets Antibody coated platelets Splenic Entrapment Platelet
destruction
Clinical features:
1. Often asymptomatic
2. Bleeding manifestations: Superficial/ deep
3. Splenomegaly is characteristically absent (in acute ITP, mild splenomegaly may be present).
Investigations
1. Platelet count: ↓;Smear: Platelets of ITP has a characteristic morphological appearance- virtually diagnostic
2. Hb, WBC count: Normal
3. Clotting profile: Usually normal (BT may be ↑)
4. Antiplatelet antibody may be detected
Treatment
 Often not required in acute ITP
 If significant bleeding present:
 Platelet transfusion
 IV IgG therapy.
2. Specific treatment: Often none offered and the patient is kept under surveillance only
 Long term Prednisolone
 Rituximab
 Newer drugs (Thrombopoietic receptor agonist):
These are used when patients don’t response to other treatments:
 Eltrombopag
 Romiplostim
 Splenectomy
 Difference between acute and chronic ITP
Acute ITP Chronic ITP
Newborns/ infants Adults
Preceded by an episode of viral infection Afebrile
Splenomegaly (mild) may present Usually absent
Often self-limiting Often needs treatment
Thrombocytopenia
Reduction in the number of platelets <1.5 lakhs/μL (normal level: 1.5-4.5 lakhs/ μL).
Etiology:
As part of pancytopenia Selective thrombocytopenia
Bone marrow disorders Immune mediated (ITP)
Non-bone marrow disorders Infection Dengue HIV
Iatrogenic Heparin induced (HIT)
Clinical features:
1. Due to thrombocytopenia:
a. Asymptomatic
b. Symptomatic: Spontaneous bleeding manifestations
Note: Risk of spontaneous bleeding increases significantly when platelet count goes <20000/ μL. A count
<10000/ μL is called “critical thrombocytopenia”.
2. Features due to underlying disease.
Investigation
1. Platelet count: ↓
2. Hb, WBC count: Normal/ ↓
3. Coagulation profile:
a. BT: ↑
b. Other parameters (CT/ PT/ INR/ aPTT) are often normal
4. Investigation(s) to confirm the underlying disease.
Treatment
Platelet transfusion
Indication:
a. Significant bleeding
b. No bleeding: 1.Platelet < 10000; 2. Before any invasive procedure that carries risk of bleeding.
2. Definitive treatment:Treatment of the underlying disease.
Hemophilia
It is a congenital coagulopathy due to deficiency of factor VIII.
Types: 1. Hemo A: Deficiency of factor VIII 2. Hemo B: Deficiency of factor IX 3. Hemo C: Deficiency of factor XI
Clinical features:
Asymptomatic: No bleeding manifestation
Bleeding: Spontaneous bleeding:
1. Superficial: Purpura, gum bleeding, epistaxis
2. Deep: GI/GU/ICH/Hemarthrosis:
3. Recurrent hemarthrosis in the same joint may lead to joint damage; resulting in restriction of movement.
Investigation
Clotting profile:
 BT: Normal
 CT: ↑
 PT, INR: Normal
 aPTT: ↑ (defect in the intrinsic pathway)
Note: If aPTT fails to normalize even after mixing patient’s serum with a normal serum, then circulating
antibody against factor VIII is suspected.
Confirmatory test: Estimation of factor VIII level/ activity
Treatment
1.Minor bleeding: Antifibrinolytic agents (prevent degradation of fibrin): Tranexamic acidAminocaproic acid
2.Major bleeding: Fresh frozen plasma
3. Supplementation of Factor VIII : Regular Factor VIII concentrate administration
von Willebrand’s disease (vWD)
It is a bleeding disorder due to congenital deficiency of von Willebrand factor (vWF) which plays an important role in:
1. Platelet aggregation and adhesion
2. Transportation of factor VIII.
Clinical features:
Bleeding manifestations:
1. Prolonged bleeding even after minor injury
eg.: After dental extraction/ from wound site/ suture site: the bleeding refuses to stop.
2. Spontaneous bleeding: Superficial/ deep.
Investigations
1. Platelet count: Normal
2. BT: ↑
3. CT: Normal (may be abnormal if severe Vwf deficiency as in that case Factor VIII transport gets affected)
4. PT, INR, aPTT: Normal.
In severe forms of vWD, aPTT may get prolonged due to reduced functional activity of factor VIII.
5. Confirmation of diagnosis by detecting vWF level/ activity.
Treatment: a. Desmopressin b. Antifibrinolytic agents: Tranexamic acid/ Aminocaproic acid.
Desmopressin stimulates release of VWF from its storage sites in endothelial cells
Coagulopathy due to Acute/ Chronic liver disease (CLD)
Etiology: Decreased synthesis of clotting factors in chronic liver disease.
Clinical features:
1. Asymptomatic
2. Symptomatic: Bleeding manifestations: may be superficial/ deep.
Investigations
1. Platelet count: May be ↓
2. BT: Normal/↑
3. CT: ↑
4. PT, INR, aPTT: ↑
Usually PT and INR get prolonged before prolongation of aPTT as factor VII has got a very short half-life.
5. Liver function test.
Treatment
1. Active bleeding or before an invasive procedure: Fresh frozen plasma
2. Treatment of underlying liver disease
3. Vitamin K: Although doesn’t have much role except in Cholestatic Liver disease, is often used!!
Coagulopathy due to vitamin K deficiency

Cause: Lack of carboxylation of vitamin K dependent factors (factor II, VII, IX, X).
Causes of vitamin K deficiency:
1. Decreased intake
2. Malabsorption
3. Cholestatic liver disease
Clinical manifestations:
1. Asymptomatic
2. Symptomatic: Bleeding manifestations.
Investigations
Clotting profile:
 BT: Normal
 CT: Normal
 PT, INR, aPTT: ↑
Treatment
1. Vitamin K: Oral/IM
2. Treatment of the underlying disease.
Disseminated intravascular coagulation (DIC)
A thrombohemorrhagic disease characterized by spontaneous bleeding as well as microvasculature thrombosis.
Triggering factors:
Acute Pancreatitis
Antental complication: IUFD/ Abruptio placentae
Bacteremia: Septicemia
Cancer: Acute promyelocytic leukemia/Ca Pancreas
Pathogenesis:
Clinical features:
D: Features of the underlying disease
I: Intravascular hemolysis are often asymptomatic
I: Ischemic injury to kidney: Acute kidney injury (AKI)
Consumptive coagulopathy:
Spontaneous bleeding, starts with superficial bleeding: oozing of blood from venipuncture/surgical site
Gum bleeding, epistaxis etc. may occur.
Investigations
1. Platelet: Mild ↓
2. Hb, WBC: Variable (depending upon the underlying disease)
3. Peripheral film: Fragmented RBCs (Schistocytes)
4. Clotting profile: all deranged: PT, INR, aPTT: ↑
5. Hypofibrinogenemia with high Fibrin degradation product (FDP)↑
Treatment
2. Supportive:
 Treat bleeding manifestations by Fresh frozen plasma
 Low dose heparin.
Acute leukemia
Malignant transformation of hematopoietic progenitor cells characterized by uncontrolled proliferation
(overproduction)+ maturation arrest of Myeloid series or Lymhocytic series.
Types: 2 types: ALL and AML.
Mechanisms of clinical manifestations: (this more or less is applicable for any leukemias)
Bone marrow Infiltration: Normal marrow cellular population is replaced by immature

cells (Leukemic cells) leading to marrow failure
Clinical features: Age group: ALL: Pediatric age group AML: Middle aged/ elderly patients.
Symptoms & signs:
Mode of presentation: Often presents with anaemia or Fever +/- focal manifestations of infection:
First clue of the disease is the characteristic peripheral blood picture
Overall clinical manifestations can be ≥ 1 of the followings:
1. Due to bone marrow failure(infiltration)
Features due to Anemia Features due to Neutropenia: Feature due to thrombocytopenia:
Breathlessness Bacteteremia: Fever and/ or Focal Bleeding manifestations:
Cardiac: palpitation manifestations of infection: Pattern:
Dizziness “Candida” i.e Fungemia Spontaneously starts OR Refuses to stop
Exercise intolerance: reduced when it should have been stopped-
Fatigue prolonged bleeding/oozing even after minor
injury)
Site:
●Superficial: Epistaxis/ Conjunctival hge /
Gum/skin: petechiae/purpura
● Deep/ Internal bleeding:
GI/GU/Hemoptysis/ ICH/ Hemarthrosis
2. Due to organ infiltration:
 Hepatomegaly
 Splenomegaly+/- consequence of massive splenomegaly: Abdominal discomfort/ dragging pain
 Lymphadenopathy Functional Gastric outlet obstruction: early satiey/ Bloating
 Gum hypertrophy
 Meningeal signs (particularly in ALL)
 Hyperuricemia:
 Asymptomatic
 Acute gout
Investigations: Aleukemic Leukemia**: Short notes: Introduction then Acute leukemia!!!
1. Blood picture:
 Hb: ↓
 WBC: typically low with lots of immature cells of different generations particularly lots of circulating blast cells
 Platelet count: ↓ Atypically Acute leukemia can come with insignificant numbers of
blast cells
2. Bone marrow: Aspiration + Biopsy which is called Aleukaemic/Subleukemic Leukemia**
Cellularity: Plenty of blast cells: >20% blast cells in marrow confirms an acute leukemic:
 Myeloblast in AML
 Lymphoblast in ALL
3. Cell surface markers: Immunophenotyping(BM aspiration sample) or Immunohistochemistry(BM biopsy
sample)
Expression of cell surface markers varies according to the lineage of Leukemia:
 ALL: CD10, CD19
 AML: B cell lineage:CD13, CD33.T-cell lineage: CD 3, CD 4, CD8
4. Cytogenetics: detects chromosomal anomalies( Translocation/deletion): helps to prognosticate disease
1. LFT
2. RFT: Urea/Cr/Na/K
3. Uric acid: ↑
4. CSF: To look for meningeal infiltration (particularly in ALL)
5. Septic screen: To find the focus of infection:
 Blood and urine: C/S  Procalcitonin
 Chest X Ray  Throat swab: Gram stain and culture-sensitivity.
 CRP
Treatment
Supportive treatment:Definitive treatment
a. Treat anemia Depends on
b. Treat thrombocytopenia Type/Subtype
c. Treat neutropenia Stage of the disease 1. Chemotherapy
d. Treat hyperuricemia: Comorbidities 2. BMT/Stem cell transplantation
Allopurinol (decreases production) Age of the patient
Febuxostat (decreases production) Cost factor
Uriacse (Uricosuric agent)
Definitive treatment of AML
1. Chemotherapy: All AML subtypes except Acute promyelocyticleukemia(APL) APL:All-transRetinoic acid.
 Intensive Chemotherapy:
a. Induction of remission: Cytarabine + Doxo/ Daunorubicin.
b. Consolidation of remission: Daunorubicin.
 Non intensive Chemotherapy: particularly of elederly patients: Azacitidine
2. Bone marrow/ stem cell transplantation: indication of which depends on
a. Response to chemotherapy
b. Comorbidities
c. Age of the patient
Definitive treatment of ALL

1. Chemotherapy:
a. Induction of remission: Cytarabine/Cyclophophamide+Vincristine+Daunorubicin+Dexamethasone+L-
asparaginase
b. Post remission Consolidation: Methotrexate or Cytarabine + L-asparaginase
c. Maintenance of remission: Methotrexate + 6 Mercaptopurine + Vincristine + Dexamethasone
If patient is bcr-abl positive, a tyrosine kinase inhibitor (TKI) is added to the above regimen.
2. Stem cell transplantation/ Bone marrow transplantation (BMT):may be indicated in certain patients
depending on:
a. Response to chemotherapy
b. Comorbidity
c. Age of the patient
3. CNS prophylaxis: effective prophylaxis to prevent CNS relapse is essential part of treatment of ALL
Treatment modalities are: a. CNS Radiotherapy b. Intrathecal Methotrexate
Chronic leukemia
CLL
Malignant transformation of lymphocytes typically characterized by overproduction of mature lymphocytosis.
Pathogenesis:
Clinical features: disease of elderly population
1. Often asymptomatic and diagnosed incidentally
2. Recurrent infection: LRTI/ URTI/ Pneumonia/ Recurrent viral infection
3. Features of organ infiltration:
 Hepatomegaly
 Splenomegaly
 Lymphadenopathy
4. Due to bone marrow failure(infiltration)
Breathlessness Bacteteremia: Fever and/ or Focal Bleeding manifestations:
Cardiac: palpitation manifestations of infection: Pattern:
Dizziness “Candida” i.e Fungemia Spontaneously starts OR Refuses to stop
Exercise intolerance: reduced when it should have been stopped-
Fatigue prolonged bleeding/oozing even after minor
injury)
Site:
●Superficial: Epistaxis/ Conjunctival hge /
Gum/skin: petechiae/purpura
● Deep/ Internal bleeding:
GI/GU/Hemoptysis/ ICH/ Hemarthrosis
Investigations
1. Blood:
 Hb: Normal/ ↓ (low:due to Bone marrow failure/ AIHA)
 WBC count: ↑ (mild to moderate): predominantly lymphocytes
 Peripheral smear: Small mature lymphocytes, presence of smear cells/ smudge cells
 Platelet count: Normal/↓( low due to ITP/Bone marrow failure)
2. Bone marrow:
 Cellularity: Increased cellularity with Lymphocytosis
 Molecular study: detects cell surface markers which get expressed in CLL: CD19, CD20, CD5, CD23
1. LFT
3. Uric acid: ↑
 Blood and urine: C/S
 Chest X Ray
 CRP
 Procalcitonin
 Throat swab: Gram stain and culture-sensitivity.
5. Evidence of autoimmune hemolytic anemia:
 Serum LDH: ↑
 Coomb’s test: +Ve.
Treatment
Supportive Definitive: 2 approaches
1. Anemia: Blood transfusion Wait and watch approach
2. Neutropenia/Infection: Antibiotics
3.
Definitive therapeutic intervention
Definitive treatment: If the patient fulfills criteria for active treatment:
Options are:
1. Chemotherapy:
 FCR regime: Fludarabine + Cyclophosphamide + Rituximab
 BR regime: Bendamustine+ Rituximab
2. Bone marrow transplantation: In selected patients who have medically refractory CLL but practically never could
be done given these patients are usually elderly
CML
It is a myeloproliferative disease characterized by relentless proliferation of cells of myeloid series but there is NO
maturation arrest (however if CML enters into its Accelerated stage it starts to behave almost like an Acute leukemia)
Pathogenesis:
1. The primary defect is reciprocal translocation between 2 arms of chromosome 22 and chromosome 9.
2. The portion of chromosome 9 which gets translocated to chromocome 22 is called Abl (Abelson murine
leukemia virus oncogene).
3. The point where chromosome 22 is broken (where the translocated portion of chromosome 9 gets attached to)
is called bcr (Breakpoint cluster region).
4. The fusion gene is called Abl-Bcr, which shows high tyrosine kinase activity, which plays a central role in the
pathogenesis of CML.
5. The abnormal chromosome is called Philadelphia chromosome, which can be detected by cytologentic studies.
6. The abnormal gene (Abl-Bcr fusion gene) can be quantified using molecular studies.
Mechanism of clinical manifestations:
Clinical features: due to ≥ 1 of the followings:

1. Due to bone marrow failure(infiltration) typically occurs if CML enters into Accelerated stage
Breathlessness Bacteteremia/“Candida” i.e Bleeding manifestations:
Cardiac: palpitation Fungemia: Pattern:Spontaneously starts OR Refuses to
Dizziness Fever and/ or Focal stop when it should have been stopped-
Exercise intolerance: reduced manifestations of infection: prolonged bleeding/oozing even after minor
Fatigue injury)
Site:Superficial/ Deep/ Internal bleeding:
2.Due to organ infiltration:
 Hepatomegaly
 Splenomegaly+/- consequence of massive splenomegaly: Abdominal discomfort/ dragging pain
 Lymphadenopathy Functional Gastric outlet obstruction: early satiey/
Bloating
 Gum hypertrophy
 Hyperuricemia:
 Asymptomatic
 Acute gout
Investigation
1. Blood:
Hb: Normal/ ↓
WBC count: ↑↑
Platelet count: Normal/ ↓ (due to marrow failure).
Peripheral film: Leukocytosis but NO significant immature cells of different generations: Abundant mature
WBCs (
 Myeloblast: Usually very few (Significant number of blast cell is seen in blast crisis/Accelerated phase,
i.e. transformation of CML into acute leukemia)
 Basophilia: Indicates an impending episode of blast crisis.
2. Bone marrow:
Cellularity:
 Myeloid hyperplasia
 Blast cells: Usually <5% (When it is 10-20%, signifies accelerated styage > 20% is blast crisis
Cytogenetic study: Detection of Philadelphia chromosome confirms the diagnosis.
Molecular study: Quantification of bcr-Abl gene.
Cytogenetic study: Detection of Philadelphia chromosome & Molecular study: Quantification of bcr-Abl gene.can also
be done on peripheral blood cells

1. LFT
3. Uric acid: ↑
4. Septic screen: To find the focus of infection: Think about Hematological malignancies……
 Blood and urine: C/S Any patient with Anemia ONLY without obvious cause
 Chest X Ray OR
 CRP Anemia + Organomegaly
 Procalcitonin OR
 Throat swab: Gram stain and culture-sensitivity. Pancytopenia
Treatment Don’t “think” about the types…let the investigation result think
1. Supportive treatment: about it!!!!
a. Treatment of anemia
b. Treatment of thrombocytopenia
c. Treatment of neutropenia
d. Treatment of hyperuricemia.
a. Medical Oncology:
Chronic phase: Tyrosine Kinase Inhibitor (TKI): Imatinib or Nilotinib or Dasatinibor or Pomatinib
 In case of intolerance/poor response: switch to another TKI,
 In case of failure of two or three TKI, consider BMT/ Stem cell transplantation
Accelerated/blastic phase Aggressive regime of a TKI or consider BMT/ Stem cell transplantation
Response to chemotherapy can be assessed by: a response is considered to be good if followings are fullfilled
Response Description
Hematological Normalisation of hematological picture and significant reduction of spleen
response
Cytogenetic response Philadelphia chromosome becomes undetectable
Molecular response Significant reduction in quantity of bcr/abl titre (quantification study)
Lymphoma
Malignancy originating in the lymphoid follicular cells with proliferation lymphoid follicular cells
Classification: 1. Hodgkin’s 2 Non-Hodgkin’s
1. Enlargement of lymphoid follicle- Lymphadenopathy
Lymph nodes commonly involved: typically Mutiregional involvement
a. Superficial:
 Cervical
 Axillary
 Epitrochlear
 Inguinal
2. Extranodal spread(organ infiltration):
a. Liver d. Pleura: Pleural effusion
b. Spleen e. Ascites
c. Bone marrow (advanced stage); resulting in
marrow infiltration/ failure
 Hyperuricemia:
 Asymptomatic
 Acute gout
Clinical features: Overall clinical manifestations can be ≥ 1 of the followings:

1. Features of lymphadenopathy: typically presents with this
 Palpable lymph nodes: multiple regions involvement: Firm, non-tender, discrete
 Mediastinal lymphadenopathy: May result in SVC obstruction/ Superior mediastinal syndrome
 Retroperitoneal lymophadenopathy: can cause Subacute intestinal obstruction
2. Features due to Extranodal spread:
 Hepato/spleno-megaly
 Pleural effusion/ ascites
 Bone marrow failure at late stage: features of anemia and/or thrombocytopenia and/or Neutropenia
 Hyperuricemia:
 Asymptomatic
 Acute gout
Investigations
1. Blood: Hb, TC, DC, Platelet count: Normal. Cytopenia due to bone marrow involvement is a late manifestation
2. CECT of chest, abdomen and pelvis (to look for lymphadenopathy)
3. Confirmation of diagnosis of lymphoma:
Ideally Excisional biopsy of a lymph node
If Excisional biopsy not feasible then Radiologically guided Core/Incisional biopsy of the most accessible
lymph node
Histopathological EXAMNIATION: Confirms the type of Lymphoma
Molecular test: gives further subtypes.
4. To assess the extent/spread of the disease: which is required for staging
o CECT of chest, abdomen and pelvis (to look for lymphadenopathy)
o Whole body PET CT scan
o Bone marrow: to look for bone marrow infiltration
1. LFT
3. Uric acid: ↑
 Blood and urine: C/S  Procalcitonin
 Chest X Ray  Throat swab: Gram stain and culture-
 CRP sensitivity.
Treatment
Treat anemia Depends on
Treat thrombocytopenia Type/Subtype
Treat neutropenia Stage of the disease 1. Chemotherapy
Treat hyperuricemia: Comorbidities 2. Radiotherapy
Allopurinol (decreases production) Age of the patient
Febuxostat (decreases production) Cost factor
Uriacse (Uricosuric agent)
Chemotherapeutic drugs used:
Hodgkin’s lymphoma Non-Hodgkin’s lymphoma
 Doxorubicin/ Daunorubicin C. Cyclophosphamide
 Bleomycin D. Doxorubicin
 Vinblastine P: Prednisolone
 Dacarbazine R: Rituximab
V: Vincristine
Myeloproliferative disorders
Characterized by overproduction of any hematopoietic cell series in an isolated manner/ simultaneously.
Causes:
Hematological Malignancy
o CML Non malignancy: (BUT can turn into a malignancy)
o Acute Leukemias o Polycythemia rubra vera
o o Essential thrombocytosis
o o Myelofibrosis
o o Myelodysplatic syndrome
Myelofibrosis (Detailed knowledge not required)
Characterized by marrow fibrosis and exuberant extramedullary hematopoiesis.
Clinical features:
1. Asymptomatic
2. Due to marrow fibrosis:
a. Marrow failure, leading to features of pancytopenia
b. Features due to anemia (earliest manifestation)
c. Features due to thrombocytopenia (bleeding manifestations)
d. Features due to neutropenia (recurrent infections).
3. Due to extramedullary hematopoiesis:
a. Significant splenomegaly (causing LUQ discomfort and sensation of fullness) ± hepatomegaly
b. Usually occurs in elderly population.
Investigations
1. Blood: Hb: ↓ (earliest and often the only abnormality on presentation) WBC, platelet count: May be ↓
 Peripheral film:
 Poikilocytosis  Bizarre looking platelets
 Teardrop cells  Leuko-erythroblastic picture.
2. Bone marrow:Marrow aspirate shows reticulin (fibrosis).
Treatment
Treatment of anemia, thrombocytopenia and neutropenia.
a. Medical:Lenalidomide/ Pomalidomide b. Bone marrow transplantation
Myelodysplastic syndrome…….(Detailed knowledge not required)
It is a hematopoietic stem cell disorder characterized by combination of pancytopenia, morphological abnormalities of blood
cells and hypercellular marrow.
Clinical features:
1. Due to pancytopenia:
 Features of anemia
 Features of thrombocytopenia
 Features of neutropenia.
2. Due to extramedullary hematopoiesis:Splenomegaly ± Hepatomegaly.
Investigations
1. Blood: Variable cytopenias
2. Peripheral film: WBC: Hyposegmented neutrophils, typically bilobed nucleus: called “PelgerHuet abnormality”.
3. Bone marrow:
 Hypercellular marrow showing “Ring sideroblast”.
 Cytogenetic study: shows characteristic abnormalities
Treatment
a. Anemia:
 RBC transfusion
 Erythropoietin
 Lenalidomide.
b. Neutropenia:
 Treatment of infections
 G-CSF.
c. Thrombocytopenia:
 Platelet transfusion
 Thromboeitin receptor agonist: Eltrombopag
a. Myelosuppressive agent: Azacitidine
b. Bone marrow transplantation.
Polycythemia rubravera (PRV)…… (Detailed knowledge not required)
Hyperproliferation of all 3 series of blood cells.
Pathogenesis: JAK2 mutation plays a central role in PRV.
Clinical features:
1. Often asymptomatic
2. Features due to ↑RBC count and associated hyper-viscosity state:
a. Headache
b. Dizziness
c. Plethoric appearance.
3. Features due to ↑WBC count:Basophilia: Pruritus typically after having a shower (due to increased histamine
release)
4. Features due to thrombocytosis: Prothrombotic state: can lead to unprovoked DVTs
5. Although not common, bleeding manifestations may occur due to functional defect of the platelets.
6. Often splenomegaly is present.
Investigations
1. Blood:
 Hb: ↑ (often markedly high and usually the earliest manifestation)
 RBC count: ↑
 RBC mass: ↑
 PCV: Abnormally ↑
 Platelet count: ↑.
2. Diagnosis is confirmed by detecting the presence of JAK2 mutation.
Treatment Medical treatment: HydroxyureaProphylactic aspirin.
Points PRV Secondary polycythemia

Hypoxia Patients are non-hypoxic Chronic hypoxic: COPD/ ILD/ Congenital heart disease
Blood cells RBC↑/WBC↑/Platelet↑ RBC↑
EPO ↓ ↑
JAK2 mutation +ve -ve
Multiple myeloma….(not a must read topic)
Malignant transformation of those hematopoietic stem cells which eventually leads to plasma cells.
Pathogenesis + Clinical features:
Investigations
1. Blood:
 CBC: Anemia (normochromic normocytic)
 WBC and platelet count: Normal (may decrease in late stage due to bone marrow infiltration and
failure)
 ESR: ↑ (due to ↑rouleaux formation from hyperviscosity state)
2. Urea creatinine: ↑
3. Globulin level: ↑
4. Serum Ca++: ↑ when ALP level is typically normal.
5. Serum Immunofixation Electrophoresis with Fractional Light Chain ratio (FLC): shows Monoclonal spike (may
be IgG/ IgA/ light chain)
6. Urine:Proteinuria (Bence Jones protein: Ig light chain)
7. Skull X-ray:Areas of osteolysis: ‘punched out lesions’.
Treatment
a. Emergency treatment of hypercalcemia: IV fluid/ IV zolendronate
b. Treatment of Chronic Kidney Disease
c. Bone protection: Bisphosphonate
a. Chemotherapy: Bortezomib + Dexamethasone + Lenalidomide
b. Bisphosphonate
c. Bone marrow transplantation (in selected patients).
Blood transfusion
Complications of blood transfusion:
1. Immediate (within minutes to hours):
a. Hypersensitivity reaction:
 Cause: Presence of antigen in donor plasma
 Clinical feature: Urticaria (itch), rash, chill and rigor; lid swelling, bronchospasm, hypotension in severe cases
 Treatment:
 Immediately stop the transfusion
 Anti-allergic: IV Diphenhydramine
 In severe cases: IV hydrocortisone/ Adrenaline.
2. Early (within hours to days):
a. Hemolytic transfusion reaction: Acute hemolytic episode precipitated by mismatch blood transfusion.
 2 types:
I. Early:
 Within hours of transfusion
 Major hemolysis
 Cause: ABO incompatibility.
II. Late:
 Occurs 4-5 days after transfusion
 Minor hemolysis
 Cause: Antigenic discrepancy (minor blood group antigens), autoantibodies form
over next few days following transfusion
 Clinical features:
Major hemolysis o Acute kidney injury (due to tubular damage by free hemoglobin)
o Blackish red Urine (due to hemoglobinuria)
o Cardiovascular: collapse
o DIC
Minor hemolysis o Mild jaundice
o Mild anemia.
 Treatment:
 Immediately stop transfusion
 Send/ resend the bag of blood and patient’s blood sample for grouping and cross-matching.
 Aggressive rehydration to prevent AKI.
b. Leukoagglutinin reaction:
 Cause: Due to antigens on WBC of the donor blood to which the recipient had already been sensitized during
previous transfusion.
 Clinical features: Fever with chill and rigor occurs usually 10-12 hours after transfusion.
 Treatment:
 Immediately stop the transfusion
 IV Diphenhydramine/ IV Hydrocortisone.
c. Transfusion related acute lung injury (TRALI): ARDS precipitated by massive transfusion.
3. Late (within months to years): Blood borne infections: HIV/HBV/HCV
INF. DISEASES
Enteric Fever
Enteric Fever includes Typhoid and Paratyphoid fever.
Organism: ● Typhoid fever: Salmonella typhi ● Paratyphoid fever: S. paratyphi A, B, C
Mode of transmission: Humans are the only natural host and reservoir. The infection is transmitted by ingestion of
food or water contaminated with feces.
Incubation period: 7-14 days
First Week:
Acute febrile illness: Fever shows a step-ladder pattern — i.e., the temperature rises over the course of each day and
drops by the subsequent morning. The peaks and troughs rise progressively over time. BUT rarely fever shows this
pattern. ++
≥ 1 of the followings
Anorexia
Bodyache (Malaise)
Body weight loss
Chill (+/- rigor)
Abdominal pain and tenderness; sometimes, fierce coliky pain in RUQ.
Relative Bradycardia- temp elevation not accompanied by a physiological increase in the pulse rate
Constipation (Monocytic infiltration in Peyer’s patches, causing inflammation and narrowing)
Diarrhoea: Sometimes, foul smelling green-yellow, liquid diarrhoea (“pea-soup diarrhea”)
Dull frontal headache
Energy lack (Malaise)
Encephalopathy: Altered sensorium/ Behavioural disturbance/Cofusion/Coma/ Carphology: picking or grasping at
own clothes or bed linens as well as imaginary objects/Delirium
This encephalopathic stage is called Typhoid state/ Muttering delirium/ Coma vigil
Second week
Already existing signs and symptoms continue + followings:
Abdominal distension
Cutaneous: Rose spots- Salmon-colored, blanching, maculopapular rash on the chest, abdomen, and back, may not be
visible in dark-skinned individuals- resolve within 2-5 days. Represent bacterial emboli to the dermis.
Enlarged organs: Soft Hepato and/or splenomegaly
Normally with each degree Farenheit rise of temp Pulse
Third week: “week of complications” rate rises by ≥ 10/min.
Already existing signs and symptoms continue + followings: Relative bradycardia= Rate of rise of Pulse <than 10/min.
Abdominal distension increases
Bowel perforation and peritonitis due to necrosis in Peyer’s patches
Investigations:
1. Hematological tests
1. CBC: Hb: Mild anemia TLC: Low to normal Platelets: Low to normal
2. LFT: Mildly abnormal Serum transaminase levels 2 to 3 times the upper limit of normal
2. Tests to confirm diagnosis:

a. Blood culture: The specificity of a blood culture is 100%.
b. Typhidot: Typhidot is an enzyme immunoassay (EIA) that rapidly detects IgG and IgM antibodies to a specific 50
kD outer membrane protein (OMP) antigen of S. typhi. Detection of IgM signifies acute enteric in the early phase of
infection while detection of both IgG and IgM indicates acute enteric in the middle phase of infection. The test
becomes positive right in the first week of fever and the results are available within one hour.
Typhidot M: A modified and improved version of Typhidot, obtained by inactivating total IgG in the serum sample,
which allows access of the antigen to the specific IgM, thereby enhancing diagnostic accuracy. If specific IgM is
detected it points towards acute typhoid infection.
1
c. Widal test: Should not be done before one week of the onset of fever (rather should not be done at all!!). With the
availability of other highly reliable tests, the importance of Widal has declined. A single Widal has no value
The test is based on the demonstration of a rising titer of antibodies in paired samples 10-14 days apart. It uses O and
H antigens of S. typhi, S. paratyphi A, S. paratyphi B and S. paratyphi C to detect antibodies in blood.
Pitfalls of Widal:
Negative in 30% of culture proven cases of enteric fever.
Prior antimicrobial treatment may adversely affect the antibody response.
False positive results may occur in other clinical conditions, such as Malaria, Typhus, Bacteremia
Treatment: 7-14 DAYS DEPENDING ON THE DRUG USED AND CINICAL RESPONSE
A. Cephalosporins: Ceftriaxone/Cefotaxime/ Cefixime
B. Chloramphenicol
C. Fluoroquinolones: Ciprofloxacin or Ofloxacin
D. Azithromycin
General Principles of blood culture
 At least 25-30 ml of blood should be collected for a good yield.
 The ideal time of obtaining a sample is when the patient is having chills or when the fever spikes
 Ideally should be taken before giving the first dose of antibiotics. However, in clinical practice OFTEN
antibiotic is initiated based on the presumptive diagnosis, and a blood culture is advised.
 A single culture should not be encouraged.
Leishmaniasis
Causative agent: Leishmania donovani
Mode of transmission: Bite of female Phlebotomine sandfly- P.argentipes
Incubation period: 1- 4 months
C/F:
1. Visceral Leishmaniasis ( Kala- azar)
Acute febrile illness: high grade spikes of intermittent fever+ absence of any significant localizing symptoms
++
Anorexia
Anaemia
Bodyache (Malaise)
Body weight loss
Chill (+/- rigor)
Cough
Diarrhoea
Dermal: Hyperpigmentation of face/hands/feet/abdomen
Post kala-azar dermal leishmaniasis (PKDL): Hypopigmented nodules/macules (simulating Leprosy) but
no hypoesthesia: May appear several years after complete recovery from kala-azar
Enlarged organ: Hepatomegaly/Splenomegaly
Endemic area: resident of/travel to
Fever- Often diagnosis is not thought of in the beginning and remains undiagnosed for a considerable period of time,
so many patients come with “PUO”
Fatigue
2. Cutaneous Leishmanisis: Systemic symptoms typically absent. Small papules/non-ulcerated plaques/encrusted
ulcers over the parts exposed to sandfly bite
3. Mucocutaneous Leishmaniasis:
Cutaneous leishmaniasis: Systemic symptoms typically absent. Small papules/non-ulcerated plaques/encrusted
ulcers over the parts exposed to sandfly bite
2
Mucosal involvement: Ulcers of nasal mucosa/septum/face +/- secondary bacterial infection. Mutilation of face
may occur
Investigation:
1. Light Microscopy: demonstration of amastigote forms of the protozoa by light microscopy using Geimsa stain.
Samples
 Peripheral blood film (easy to obtain but have low detection rates)
 Bone marrow aspirate
 Lymph node aspiration
 splenic aspirate (highest yield but carries the risk of splenic rupture)
2. Culture of the organism from any of the tissue samples is also a sensitive method but requires special culture
techniques. Also, culture facilities are not routinely available.
3. Serologic diagnosis: It is the most widely used indirect method of diagnosis.
Direct Agglutination Test (DAT) and Immunochromatographic Test (ICT) using rK-39 antigen are most widely
accepted because of their high sensitivity
4. Molecular diagnosis: PCR-based nucleic acid amplification techniques have the advantage of higher sensitivity
and also require peripheral blood as test specimen rather than invasive tissue sampling such as bone marrow
aspirate or lymph node biopsy for light microscopy; however the facility is available only in referral centers and not
suitable for field diagnosis as it requires specialized equipment.
5. Hematological tests: Hb: Anaemia WBC: Leukopenia with Monocytosis; Increased Globulin
Treatment:
1. Pentavalent Antimonial compounds: Sodium Stibogluconate: Once a first-line treatment for visceral
leishmaniasis, these drugs are now almost obsolete in India because of rising incidence of drug resistance,
particularly the northern states like Bihar.
2. Amphotericin B: Liposomal Amphotericin B- a potential advantage of liposomal amphotericin B is short course
treatment- ranging from single dose infusion to total dose administered over 4-5 days.
3. Miltefosine: This phospholipid-derivative anti-leishmania drug has cure rates comparable to amphotericin B and
has the added advantage of ease of oral administration.
4. Paramomycin
5. Pentamidine Isothianate
6. Sitamaquine: This is another oral drug undergoing evaluation in clinical trials.
It has been advocated to administer these drugs in various combinations. It has added benefit of reducing drug
toxicity and treatment duration in addition to improving patient compliance and reducing treatment cost.
Leprosy
Organism- Mycobacterium leprae
Incubation period- Months to years
Mode of transmission- probably transmitted by droplets from the nose and mouth when people are in close and
frequent contact with an infectious person.
Spectrum of the disease- clinical course depends on pt’s immune status-
a. If the immune response is ineffective Lepromatous disease develops (dominated by histiocytes full of bacilli but
few lymphocytes)
b. If the immune response is vigorous Tuberculoid disease develops( granulomatous inflammation containing
epithelloid cells and lymphocytes but few or no bacilli)
Between these two poles lie those with borderline disease.
3
Tuberculoid (TT),
1 or >1 hypopigmented skin macules or anaesthetic patches (because of
Paucibacillary Borderline damaged peripheral nerves that has been attacked by host’s immune cells)
tuberculoid (BT)
Skin lesions resemble tuberculoid leprosy but are more numerous and
irregular; large patches may affect a whole limb
midborderline or Peripheral nerve involvement with weakness and loss of sensation is
Multibacillary borderline (BB) common. This type is unstable and may become more like lepromatous
leprosy or may undergo a reversal reaction becoming more like the
tuberculoid form.
Borderline Symmetric skin lesions/ nodules/ plaques
Multibacillary lepromatous (BL),and frequent involvement of the nasal mucosa resulting in nasal
Lepromatous (LL) congestion and epistaxis but nerve damage is a late feature.
Clinical features
1. Cutaneous-
1. Hypopigmented anaesthetic macules/papules/annular lesion with raised erythematous rims
2. Eryhthema Nodouosum- in Lepromatous disease
2. CNS: Nerve lesions- Peripheral neuropathy due to involvement of major sensory nerves usually
3. Lepra Reaction- ….(important: Short note)
During the course of leprosy, immunologically mediated episodes of acute or subacute inflammation known as Lepra
reactions may occur in up to 25% of patients with paucibacillary leprosy and as much as 40% in multibacillary
leprosy.
These reactions may rapidly cause severe and irreversible nerve damage and must always be treated promptly.
During a lepra reaction, do not interrupt leprosy multidrug therapy. Treatment with multidrug therapy reduces the
frequency and severity of lepra reactions.
There are two types of reactions – Reversal Reaction (or Type 1) Erythema Nodosum Leprosum (ENL or Type 2)
Both the types of reactions can occur before the start of treatment, during treatment, or after the treatment has been
completed. Both types can be divided into mild or severe.
Type 1 (Reversal Reaction) Type II (ENL)
1. Delayed hypersensitivity 1. Antigen antibody reaction
2. Occurs in PB and MB type of cases (Borderline group) 2. Seen in MB cases only (BL & LL type)
3. Skin lesions suddenly become reddish, swollen, warm, 3. Red, painful, tender, sub cutaneous nodules on face,
painful, and tender. New lesions may appear. arms, legs usually bilateral symmetrically.
4. Nerves close to skin may be enlarged, tender and 4. Nerves may be affected but not as common or severe
painful (neuritis) with loss of nerve function (loss of as in Type 1
sensation and muscle weakness) and may appear
suddenly or rapidly
If any of the following sign is found, the reaction should If any of the following signs is found, the reaction
be treated as severe: should be treated as severe:
a. Loss of nerve function i.e. loss of sensation or muscle a. Pain or tenderness in one or more nerves, with or
weakness. without loss of nerve function
b. Pain or tenderness in one or more nerves. b.Ulceration of ENL nodules
c. Marked swelling & redness in skin patches. c. Pain and/or redness of the eyes, with or without loss
d. A red, swollen patch on the face, or overlying another of visual acuity
major nerve trunk. d.Painful swelling of testis or of the fingers
e. A skin lesion anywhere that remains ulcerated. e.Marked arthritis or lymphadenitis
f. Marked oedema of the hands, feet or face.
5. Other organs - Not affected 5. Organs like eyes, testis, and kidneys may be affected
6. General symptoms - Not common 6. Fever, joints pain, red eyes with watering
4
Investigations
1. Skin smear examination-Look for the presence of acid-fast bacilli under oil immersion Lens
Bacteriological Index (BI)
0= No bacilli seen in 100 fields 1+= 1 to 10 bacilli in 100 fields 2+= 1 to 10 bacilli in 10 fields
3+= 1 to 10 bacilli, in each field 4+= 10 to 100 bacilli in each field 5+= 100 to 1000 bacilli, in each field
6+= >1000 bacilli, in each field
2. Histopathology of skin or nerve biopsy
A. Punch (5 mm) biopsy or incision biopsy for histopathological examination may help.
B. Specimen can be taken from just inside the edge of the lesion/cutaneous branch of peripheral nerve- the common
nerve for biopsy includes the index branch of Radial cutaneous nerve and Sural nerve unless any other superficial
sensory nerve is affected.
C. Presence of lepra bacilli in or around the nerve is diagnostic, but only granuloma or infiltration without support
of clinical signs may mislead.
D. FNAC/Biopsy from the lymph gland is usually helpful in suspected lepra reaction type 2.
3. Radiological examinations
a. X-rays- osteoporosis/ fractures of small bones/ absorption of bones/ sequestra
b. USG of nerve trunks or internal organs e.g. testes, reticulo-endothelial organs may help in judging the diagnosis
and prognosis of complicated cases.
Treatment-….important
Standard Rx regimen for MB leprosy- Standard Rx regimen for PB leprosy-
Rifampicin..................600 mg once a month Rifampicin..................600 mg once a month
Clofazimine................300 mg once a month Dapsone.....................100 mg daily
+ 50 mg daily
Dapsone.....................100 mg daily Duration: 6 months
Duration: 12 months
Treatment of Lepra reaction-

Type 1
1. Corticosteroid – Oral Prednisolone- reaction is generally controlled within a few days and the dose is then
gradually reduced weekly or fortnightly and eventually stopped. Most reversal reactions and neuritis can be treated
successfully with a standard 12 week course
Type 2 (erythema nodosum leprosum)
1. Analgesics- Paracetamol
2. Corticosteroids- oral Prednisolone
3. Clofazimine/Thalidomide- patients with severe type 2 reactions, who do not respond to corticosteroids or in
whom corticosteroids are contraindicated, Clofazimine at high doses or thalidomide may be used under close
medical supervision. Clofazimine often requires 4-6 weeks before an effect is seen, and therefore must never be used
as monotherapy for treatment of severe type 2 reactions. However, it may be useful for reducing or withdrawing
corticosteroids from patients who have become dependent on corticosteroids.
Syphilis
Systemic sexually transmitted disease (STD) caused by the spirochete-Treponema pallidum.
Mode of transmission-
1. STD
Vaginal, anal, or oral sex through direct contact with a syphilis chancre
Person to person during foreplay, even when there is no penetrative sex (less common)
2. Pregnant mother with syphilis to fetus
5
Clinical stages/types
Primary Stage (highly infectious)
1. One or more chancres appear- usually firm, round, small, and painless at the site of infection (most often the
genital area) 10 to 90 days after infection.
2. The chancres heal on their own in 3-6 weeks
3. Patient is highly infectious in the primary stage
Secondary Stage (highly infectious)
1. Rashes occur as the chancres fade or a few weeks after the they heal
2. Rashes typically appear on the palms of the hands, the soles of the feet, or on the face, but also may appear on
other areas of the body.
3. Sometimes wart-like “growths” may appear the genital area.
4. Rashes and syphilitic warts tends to clear up on their own within 2-6 weeks, but may take upto 12 weeks.
Late (Tertiary) stage (not infectious)…….3C…(important)
● Cutaneous- Lesions in the skin and bones (gummas)
Gummatous syphilis usually occurs years after the initial infection, with an average of 15 years.
Characterized by the formation of chronic gummas which are soft, tumor-like balls of inflammation of variable size
typically affecting skin, bone, and liver
● Central nervous system (Neurosyphilis) - Infection involving the central nervous system- typically occurs 4 to 25
years after the initial infection
Asymptomatic
Syphilitic meningitis
General paresis- dementia/personality disturbance
Tabes dorsalis-
1. Dorsal column lesion leading to loss of deep sensations (position and vibration sense)
2. Electric shock like pain in the extremities
Argyll Robertson pupils (ARP) - Bilateral small pupils with loss of light reflex but Accommodation Reaction
preserved.
● Cardiovascular- Usually occurs 10–30 years after the initial infection. Syphilitic aortitis which may result in Aortic
aneurysm formation and AR
Congenital Syphilis Severity ranges from asymptomatic to fatal.
1. Early manifestations - spontaneous abortion, stillbirth, encephalitis, generalized skin rash, rhinitis
(“snuffles”), hepatic dysfunction, consumption coagulopathy, multiorgan failure
2. Late manifestations – usually not apparent at birth include osteitis of long bones, maxillofacial and dental
malformations, keratitis, hearing loss, and chronic neuropsychological deficit
Diagnosis-
1. Dark-field examinations or direct fluorescent antibody tests of chancre tissue are the definitive methods for
diagnosing primary and secondary syphilis
2. A presumptive diagnosis is possible with sequential serologic tests (e.g. VDRL, RPR), using the same method
each time. A 4 fold change in titer (e.g. from 1:8 to 1:32) is usually considered to be clinically significant
Treatment-
Primary/ Secondary/ or Early Latent <1 year- IM of Benzathine Penicillin G single dose
Latent >1 year or Latent of Unknown Duration- IM of Benzathine Penicillin G in 3 doses each at 1 week intervals
Neurosyphilis- IV of Crystalline Penicillin G 10-14 days
Congenital Syphilis-IV Crystalline Penicillin G during approx. first 3 weeks of life
6
Malaria
Agent: P. falciparum and P. vivax - In India mainly these 2
P. ovale, P. malariae
Incubation period: Vivax 8-17 days; Falciparum 9- 14 days
Mode of transn: Bite of infected female Anopheline mosquito (female bites are responsible for Loveria as well!!)
C/F-
1. Uncomplicated malaria (both Falciparum and Vivax)
Acute febrile illness- With a periodicity of 48 or 72 hours can be seen in Non falciparum malaria
or
Continuous fever
A febrile episode often passes through 3 stages-
1. Cold stage- ½ - 1 hour- feels very cold+ chill+ rigor
2. Hot stage- 2-upto 6 hours-feels intensely hot
3. Sweating stage- fever comes down with drenching sweat (with or without Paracetamol)
++
Anorexia
Bodyache/body weakness
Chill (+/- Rigor)
Decresed energy level (malaise)
Eye- Mild icterus
Enlarged Spleen +/- Liver
2. Complicated Malaria/Cerebral Malaria- usually occurs in some Falciparum patients*important-LQ/SN

F/O uncomplicated disease + ≥ 1 Following pathophysiological events can occur
ARDS- SOB/Tachypnoea/Low O2 saturation/bilateral crepts
AKI- Low urine output/Uremic encephalopathy/Acidotic breathing
Anaemia- severe hemolytic anaemia (Intravascular hemolysis)
Bilirubin ↑↑ - Icterus (hyperbilirubinemia is due to hemolysis)
Black water fever/hemoglobinuria (due to Intravascular hemolysis)
CNS- Encephalopathy…its “ABCDE”!!
Circulatory collapse - shock- Hypotension/feeble pulse/tachycardia
CBG- Hypoglycemic spells
DIC- spontaneous bleeding
Eventually some patients develop multi-organ failure
Investigations-
To diagnose Malaria
a. MP detection in peripheral smear-
Thick and thin film- thick reliable for searching/thin- for identification of species
b. Rapid Diagnostic Test- Detection of Vivax and Falciparum antigen (Malarial dual antigen)
Some of the Ag detection kits may show positive result up to 3 weeks after parasite clearance. In these cases, results
should be correlated with microscopic diagnosis.
To diagnose/monitor complications- In a suspected complicated case following tests are indicated
a. FBC e. ABG
b. Urea/Cr/Na/K f. FDP
c. CBG monitoring- tendency of hypoglycemia g. CxR
d. LFT
7
Treatment (Imp) Ans. Model 1 (particularly if Q.- Rx of severe/complicated/Cerebral Malraia)Imp
Treatment - a. Antimalarials b. Supportive Rx
a. Antimalarials
Day 1- 10mg/kg
1. P. vivax cases after 24 hours
a.Chloroquine- 25 mg/kg over 3 days Day 2- 10mg/kg
after 24 hours
Day 3- 5mg/kg
b. To prevent quick relapse- Primaquine should be given at a dose of 0.25 mg/kg body weight daily for 14
days with pretreatment estimation of G 6 PD level.
2. P.falciparum cases- Complicated or Uncomplicated Day 1: Artesunate + Sulfadoxine-Pyrimethamine
a. Artemesinin Combination Therapy (ACT)- 1st line: total 3 days Day 2: Artesunate + single dose of Primaquine
if not feasible/ available Day 3: Atresunate
b. Quinine + (Doxycycline OR Clindamycin)- 2nd line: total 7 days Rx

ACT regimens
Artesunate + Sulfadoxine-Pyrimethamine (recommended in the National Programme for all India except NE states)
Artemether + Lumefantrine (NE states)
Artesunate+ Amodiaquine
Artesunate + Mefloquine
b.Supportive- Especially for complicated Malaria- Rx depends on specific complications
ARDS- Intubate and Ventilate
AKI- Dialysis
Anaemia- Packed cell transfusion
Circulatory collapse- IV fluid resuscitation + Maintenance fluid therapy+/- Vasopressor
DIC- FFP
Drugs- supportive drugs
a. Antipyretic- Paracetamol
b. Antiemetic- Ondansetron
c. Anticonvulsant- Levetiracetam/Phenytoin
Ans. Model 2 (particularly if Q.- Rx of severe/complicated/Cerebral Malraia)Imp
A-Admit
A-Airway- to be protected if Comatose/ARDS suspected
B-Breathing- Ventilate if ARDS
B-Blood biochemistry monitoring during critical stage- Electrolytes/Ur/Cr/ABG/FBC/CBG
B-Bladder and bowel care B- Bed sore prevention
C-Circulation- IV fluid resuscitation + Maintenance fluid therapy+/- Vasopressor if in shock
C-Catheterize to monitor urine output
D-Drugs- Antimalarials
Antipyretic
Antiemetic AS ABOVE
Anticonvulsant
D-Dialysis for AKI
D-Diet- Nutritious diet- Orally or through R/T if comatose
D- DVT prevention
DIC- FFP
(if above fails, D- death certificate!!)
8
Complicated Malaria pathogenesis/pathophysiology (Short notes)
The following are some of the factors known to play a role in the clinical manifestations of severe/complicated
malaria infection.
 Species of parasite: Only P. falciparum causes severe/complicated malaria
 Host Immunity
 The degree of parasite drug resistance that prevails locally
Processes Contributing To Specific Complications
AKI-Acute tubular necrosis due to tubular damage by endogenous ‘tubulotoxin’- free Hb
ARDS-Pulmonary oedema (non-cardiogenic) possibly through release of cytokines which is a direct effect of
parasites sequestered in the lungs
Anaemia- Intravascular haemolysis due to the destruction of red cells that contain parasites.
Bilirubin↑ (Jaundice)- due to haemolysis and partly to liver dysfunction
Black water fever/ Haemoglobinuria- massive intravascular haemolysis leading to release of free Hb in circulation
Cerebral Malaria- sequestration of infected RBCs in the brain
Circulatory collapse (Shock) inadequate cardiac output +/- poor tissue perfusion
CBG fall (Hypoglycaemic tendency)- Impaired Neoglucogenesis & release of glucose by the liver + increased
utilization in the tissues + Quinine s/e (stimulates release of insulin)
DIC- release of procoagulant cytokines
HIV
2 types: HIV1 and HIV2. HIV1- more virulent, more infective & causes majority of infections globally.
Clinical stage 1
Asymptomatic Persistent generalized lymphadenopathy
Clinical stage 2
Angular cheilitis
Body wt. loss- Moderate (≤10% of presumed or measured body weight)
Buccal ulceration recurrent
C ××
Dermal- Papular pruritic eruptions/Dermatitis (Seborrhoeic)
ENT infection- Recurrent sinusitis/tonsillitis/otitis media/pharyngitis
Fungal nail infections
G ××
Herpes zoster
Clinical stage 3
Acute necrotizing ulcerative stomatitis/gingivitis/periodontitis
Body wt. loss- severe (= >10% of presumed or measured body weight)
Bacterial infections-Pneumonia/Empyema/Bone or Joint /Meningitis/Bacteraemia
Candidiasis- Persistent oral
Cytopenias
Chest- Pulmonary TB (active)
Diarrhoea for longer than one month
E ××
Fever of unknown origin (> 99.6 F intermittent or constant, for longer than one month)
Stage 4 (Clinically AIDS defining illness)
Any disseminated mycosis- coccidiomycosis/ histoplasmosis
Bacterial pneumonia- Recurrent severe
Chronic herpes simplex infection- more than 1 month- oro-labial/genital/anorectal/visceral at any site
Candidiasis Oesophageal/tracheal/bronchial/lungs
CNS toxoplasmosis
Cryptosporidiosis Cryptococcosis-meningitis CMV- retinitis or infection of other organs Cystoisosporiasis
Disseminated non-tuberculous mycobacterial infection
Extrapulmonary tuberculosis
9
F ×× G××
AIDS is defined as presence of any one of the following in a
HIV wasting syndrome person with confirmed HIV infection
HIV-associated nephropathy ● Clinical diagnosis (presumptive or definitive) of any stage 4
HIV-associated cardiomyopathy condition
HIV encephalopathy ● Immunological diagnosis first-ever documented CD4 count
Invasive cervical carcinoma less than 200 per mm3 or %CD4+ <15%
Jiroveci- Pneumocystis jiroveci pneumonia
Kaposi’s sarcoma
Leishmaniasis- Atypical disseminated Leishmaniasis
Lymphoma
Leukoencephalopathy-Progressive multifocal leukoencephalopathy
Investigation
For symptomatic persons: sample should be reactive with 2 different kits. (kit= ELISA test kit for Anti HIV)
For asymptomatic persons: the sample should be reactive with 3 different kits
Blood
Anti HIV
A1
A1 +ve A1 -ve
Report: Non-Reactive
A2
Anti HIV
A1+ve, A2+ve A1+ve, A2-ve

Report Reactive
Tiebreaker A3
Anti HIV
A1+ve, A2-ve, A3+ve A1+ve, A2-ve, A3-ve

Report: Reactive Report: Non-Reactive
Essential tests Additional tests
FBC For all patients to be started on ART (as
Urine R/E and M/E per the physician’s decision depending
FBG/PPBG on clinical presentation)
Urea, Creatinine USG abdomen
SGPT Sputum for AFB
VDRL CSF analysis
CD4 count
CxR
Pregnancy test (if required)
Symptoms and signs directed investigations for ruling out Ols
Tests for Special Situation Tests for monitoring purpose
HBsAg: for all patients if facility is available CD4, Hb, TC, DC, SGPT
Anti - HCV antibody
Treatment- Principles
1. ART if indicated
2. Rx of opportunistic infection
3. Rx of specific clinical situation(s)
4. Contact tracing and monitoring them +/- Rx if indicated
10
1. ART…(short notes)
Drugs
Nucleoside reverse transcriptase inhibitors (NRTI)- Zidovudine/ Lamivudine/ Didanosine/ Emtricitabine
Nucleotide reverse transcriptase inhibitors (NtRT)- Tenofovir
Non-nucleoside reverse transcriptase inhibitors (NNRTI)- Nevirapine/ Efavirenz
Protease inhibitors (PI)- Saquinavir/Ritonavir/Indinavir
Initiation of ART based on CD4 count and WHO clinical staging

1. Clinical Stage I and II - Start ART if CD4 ≤ 500 cells/mm3
2. Clinical Stage III and IV- Start ART irrespective of CD4 count
3. HIV and TB co-infection (Pulmonary/ Extra-Pulmonary)-Start ART irrespective of CD4 count and type of TB
4. HIV and HBV / HCV co-infection
[
 with significant evidence of chronic Liver disease - Start ART irrespective of CD4 count
 without significant evidence of chronic Liver disease - Start ART if CD4 ≤ 500 cells/mm3
5. All pregnant and breast feeding patient: All clinical stages- Start ART irrespective of CD4 count
Regimes
Zidovudine/Tenofovir + Lamivudine + Nevirapine- 1st line for who are not on concomitant ATDs
Zidovudine/Tenofovir + Lamivudine + Efavirenz- 1st line for who are on concomitant ATDs
Tenofovir + Lamivudine + Efavirenz- 1st line for all with Hepatitis B and/or Hepatitis C co-infection
Prophylaxis of opportunistic Infections (OIs)

Co-trimoxazole is effective against several organisms- Toxoplasma/PJ and several others causing diarrhoea in HIV.
Dapsone is an alternative for pts with Sulpha drug allergy.
Co-trimoxazole prophylaxis recommendations
1. Any WHO clinical stage with CD4 < 250
2. Symptomatic patients with any clinical stage with CD4 < 350
3. WHO stage 3 or 4 irrespective of CD4 count
Stopping prophylaxis- If CD4 count >250 for at least 6 months and If patient is on ART for at least 6 months & is
asymptomatic and well
Immune reconstitution inflammatory syndrome (IRIS)

It is a paradoxical worsening of an existing infection or disease process or appearance of a new infection/disease
process soon after initiation ART in HIV-infected patients.
ART initiation in HIV-infected patients leads to recovery of CD4+T cell numbers and restoration of protective
immune responses against a wide variety of pathogens, resulting in reduction in the frequency of opportunistic
infections and prolonged survival. However, in a subset of patients, dysregulated immune response after initiation of
ART leads to IRIS.
The immunopathogenesis of the syndrome is unclear but it appears to be result of unbalanced reconstitution of
effector and regulatory T-cells, leading to exuberant inflammatory response in patients receiving ART.
C/F Majority of patients with IRIS have a self-limiting disease course. Common manifestations are due to infection
with followings-
Mycobacteria: Myco. TB; Myco. avium complex; Mycobacterium leprae

Protozoa: Toxoplasma; Microsporidia; Leishmania; Cryptosporidia
Fungal infections: Cryptococcus; Pneumocystis jiroveci; Histoplasma; Candida
Bacteria: Bartonella
Viruses: Herpes simplex; Herpes zoster; CMV; Parvovirus B19; Molluscum contagiosum
Helminth: Schistosoma; Strongyloides.
Treatment: ART is usually continued and treatment for the associated condition optimized.
11
Pneumocystis jiroveci/Pneumocystis carini
Pneumocystis jiroveci is one of the most common opportunistic infection in persons with HIV infection.
Pneumocystis is a genus of unicellular fungi found in the respiratory tracts of many mammals and humans.
Groups are at risk
Persons with HIV infection whose CD4 + below 200/µL and who are not receiving PJP prophylaxis
Persons with primary immune deficiencies
Long-term immunosuppressive regimens
Hematologic and nonhematologic malignancies
C/F-Typically causes Pneumocystis jiroveci/carini Pneumonia (PJP or PCP) - an interstitial Pneumonitis
Progressive exertional dyspnea Tachypnea
Fever Fever
Nonproductive cough Tachycardia
Chest discomfort Pulmonary: mild crackles and rhonchi but normal in
Weight loss many pts
Hemoptysis
Investigation
1.LDH level- usually elevated in PJP who are infected with HIV- high sensitivity but not a specific marker because
other disease processes can result in an elevated LDH level. LDH levels appear to reflect the degree of lung injury.
(BUT high LDH is NOT a diagnostic feature/criteria!!)
2. CxR- often surprisingly normal
3. HRCT
4. Sputum induction- Pneumocystis organisms are found in sputum induced by inhalation of a hypertonic saline
solution. Expectorated sputum has a very low yield.
5.ABG- Hypoxia
Treatment
1. TMP-SMX
2. 2nd line agents- Pentamidine OR (Dapsone + Pyrimethamine) OR Atovaquone
3. Corticosteroids-as adjunctive therapy in patients with HIV infection who have severe PJP as defined by a room air
PaO2 < 70 mm Hg
Skin manifestations of HIV

Conditions in Patients with CD4+ Counts Below 200/µL who are not on ART
Photodermatitis
Prurigo Nodularis
Molluscum
Diseases that do not go away even with ART
Eczema
Xerosis
Kaposi’s sarcoma
Human papilloma virus-associated warts
Conditions emerging with Immune Reconstitution under ART
Acne
Staph infections- frequently MRSA
Erythema nodosum
Opportunistic infection in AIDS

Bacterial Infections- Strep.pneumoniae, Staph.aureus, H. influenzae, Pseudomonas
Candida Infections- Orpharyngeal/ Oesophageal/Invasive or disseminated
Coccidioidomycosis-Pneumonia/CNS
Cryptococcosis-Meningoencephalitis
Cryptosporidiosis-relapsing/chronic diarrhoea or cholera-like diarrhoea
Cytomegalovirus-chorioretinitis/ pneumonia/Colitis
12
Giardiasis-chronic diarrhoea
Herpes Simplex Virus perioral vesicles/ Genital infection/ keratitis/ encephalitis
Histoplasmosis Meningitis/ Progressive disseminated histoplasmosis (PDH)
Human Herpesvirus 8 Disease- Kaposi sarcoma (KS)
Human Papillomavirus
Influenza
Isosporiasis (Cystoisosporiasis)
Malaria
Microsporidiosis
Mycobacterium avium Complex Disease
Mycobacterium tuberculosis
Pneumocystis jirovecii Pneumonia
Progressive Multifocal Leukoencephalopathy
Syphilis
Toxoplasmosis
Varicella-Zoster Virus
Diarrhoea in HIV
The most common of the opportunistic infections that cause diarrhoea in patients with AIDS are-
CMV infection
Cryptosporidiosis Microsporidiosis
Giardiasis MAC infection (Myco. avium & Myco. intracellulare)
CMV-colitis associated with fever, crampy abdominal pain, and frequent often bloody stools.
Cryptosporidium-causes diarrhoea which can be transient or may last for months in patients with AIDS, causing
malabsorption, gradual debilitation through dehydration, and metabolic abnormalities
Microsporidia- Enterocytozoon bieneusi and Encephalitozoon intestinalis are the 2 microsporidia found in patients
with AIDS.
MAC- Symptoms caused by MAC infection are usually evidence of severe immunodeficiency. Systemic MAC
infection can cause spiking fever and lethargy. Diarrhoeal illness caused by MAC can cause these as well.
Investigations
1. 3 stool specimens- ova, parasites, C difficile, common enteric bacteria, Cryptosporidium, and Microsporida. 2.
Blood cultures-for febrile patients
2. Colonoscopy when other tests do not result in a diagnosis
Treatment-
CMV-colitis- Ganciclovir or Foscarnet. Effective HAART will often reduce the need for prolonged maintenance
therapy.
Cryptosporidium- No effective therapy- Paromomycin sometimes offers slight symptomatic relief.
Microsporidia: Albendazole
MAC: prolonged therapy with ≥ 2 1st line ATDs + ART
AIDS
AIDS is defined as presence of any one of the following in a person with confirmed HIV infection
 Clinical diagnosis (presumptive or definitive) of any stage 4 condition
 Immunological diagnosis first-ever documented CD4 count less than 200 per mm3 or %CD4+ <15%
Stage 4 (Clinically AIDS defining illness)
Any disseminated mycosis- coccidiomycosis/ histoplasmosis
Bacterial pneumonia- Recurrent severe
Chronic herpes simplex infection- more than 1 month- orolabial/genital/anorectal/visceral at any site
Candidiasis Oesophageal/tracheal/bronchial/lungs
CNS toxoplasmosis
Cryptosporidiosis
Cryptococcosis-meningitis
CMV- retinitis or infection of other organs
Cystoisosporiasis
13
Disseminated non-tuberculous mycobacterial infection
Extrapulmonary tuberculosis
F ×× G××
HIV wasting syndrome
HIV-associated nephropathy
HIV-associated cardiomyopathy
HIV encephalopathy
Invasive cervical carcinoma
Jiroveci- Pneumocystis pneumonia
Kaposi’s sarcoma
Leishmaniasis
Lymphoma
Leukoencephalopathy-Progressive multifocal leukoencephalopathy
Investigation
1. Symptomatic persons: sample should be reactive with 2 different kits. (kits= ELISA test kit for Anti HIV)
2. Asymptomatic persons: the sample should be reactive with 3 different kits
3. Other relevant tests to diagnose underlying opportunistic infection/problems
Treatment- Principles
1. ART 3. Rx of specific clinical situation(s)
2. Prevention/Prophylaxis against of 4. Contact tracing and monitoring them +/- Rx if
opportunistic infection indicated
ART Regimes
Zidovudine/Tenofovir + Lamivudine + Nevirapine- 1st line for who are not on concomitant ATDs
Zidovudine/Tenofovir + Lamivudine + Efavirenz- 1st line for who are not on concomitant ATDs
Tenofovir + Lamivudine + Efavirenz- 1st line for all with Hepatitis B and/or Hepatitis C co-infection
Prophylaxis of opportunistic Infections (OIs)
Co-trimoxazole is effective against: Toxoplasma
PJ
Several organisms causing diarrhoea in HIV.
Dapsone is an alternative for pts with Sulpha drug allergy.
Dengue
Causative agent: Dengue virus Vector: Aedes aegypti Reservoir of infection: Man & mosquito
Incubation period: 7- 10 days
C/F
1. Febrile phase:Acute febrile illness
++
Bodyache: may be severe (“break bone fever”): Arthralgia+ Myalgia + headache+ retro-orbital pain
Chill
Cutaneous: initially flushed but on day 2-3 day of fever maculopapaular rash may appear which usually spares
palm/sole
Complications: Usually appear (if at all) between day 3 to day 7 of illness however may appear earlier.
Early warning signs are
 Abdominal pain/tenderness  Drowsiness
 Bleeding manifestations  Dehydration
 Blood parameters: ↑↑Hct/ Falling Platelet  Enalrged liver: more than 2 cm
 Clinical evidence of fluid accumulation
Decreased energy level
Eye: conjunctival congestion
Enlarged organ: Hepato and/or Splenomagaly (clinical or radiological)
14
2. Critical phase: Complications if at all classically start between day 3 to day 7 of illness
A. Hypovolemia: DSS loss of plasma volume Volume depletion

Increased capillary permeability leads to Plasma leakage
Accumulation of fluid in serous cavities
1. Loss may be mild/moderate /severe: depending on the degree of volume loss patient may develop manifestations
of different degrees of dehydration
Asymptomatic Dry throat
BP: normal or low or Pulse pressure < 20 mm of Hg Drowsiness/Delirium
CRT: Normal or prolonged (more than 2 seconds) Excessive thirst
Decreased urine output & Dark urine Extremity: cold/clammy
Dry skin & mucous membrane Pulse: rapid +/- weak volume
2. Accumulation of Fluid in serous cavities: Fluid: Ascites/Pleural effusion

(may be clinically obvious or radiologically seen)
B. Hemorrhage: DHF: Due to Thrombocytopenia
Asymptomatic
Bleeding manifestations: Spontaneous bleeding:
 Superficial: Purpura/Ecchymosis/Epistaxis/gum bleeding
 Deep seated bleeding: GI bleed/GU bleed /ICH/Intra-abdominal bleeding
Circulatory: Shock due to severe blood loss
C. Refractory shock and/or Cytokine release may lead to following consequences in some patients of DHF/DSS:
ARDS Dysfunction of Organs (Multiorgan
Acidosis dysfunction/failure)
Bleeding (severe)  Acute Kidney Injury
Circulatory failure  Acute Liver Injury
DIC
A+B+C= answer for “Complications of Dengue”
For Short Notes Lovers!!

Risk factors for DHF
Virus factors: Host factor:
Virulence of strain Pre-existing anti-dengue antibody due to previous infection
or
DHF risk is greatest when DEN-2 follows DEN-1 maternal antibodies in the
infants
Hyperendemic transmission: locations with ≥ 2 serotypes circulating simultaneously
Under NVBDCP the case definitions recommended by WHO are being followed………(short notes)
Dengue Fever: Clinical description

An acute febrile illness of 2-7 days duration with two or more of the following manifestations:
 Headache  Arthralgia
 Retro-orbital pain  Rash
 Myalgia  Haemorrhagic manifestations
Criteria for Dengue Haemorrhagic Fever and Dengue Shock Syndrome

Tourniquet test: performed by inflating a BP cuff to a
Dengue Haemorrhagic Fever: (….short notes)
midpoint between the SBP & DBP for 5 minutes. The
a).A probable or confirmed case of dengue
test is considered positive when ≥10 petechiae/2.5 cm2
Plus
are observed. In DHF, the test usually gives a definite
b). Haemorrhagic tendencies evidenced by ≥1 of the following
positive test with ≥20 petechiae.
15
1. Positive tourniquet test
2. Superficial bleed: Petechiae, ecchymoses or purpura
3. Mucosal bleed: GI bleed/GU bleed
Plus
c). Thrombocytopenia
Plus
Evidence of plasma leakage due to increased vascular permeability, manifested by one or more of the following:
1. A > 20% rise in average haematocrit for age and sex
2. A > 20% drop in haematocrit following volume replacement treatment compared to baseline
3. Signs of plasma leakage: pleural effusion, ascites
Dengue Shock Syndrome:…..(short notes)
All the above criteria for DHF
Plus 1. BP: hypotension narrow pulse pressure
Evidence of circulatory failure manifested by ≥ 1 of these: 2. rapid and weak pulse
3. cold and clammy skin
4. restlessness
Grading of DHF (….short notes)
Grade Symptoms/signs Laboratory findings
DHF Grade DF + Platelet count less than
1 Positive tourniquet test 100,000/cu.mm
Evidence of Plasma leakage Haematocrit rise 20% or more
DHF Grade Above signs and symptoms + Platelet count less than
2 Evidence of spontaneous bleeding: Superficial and/or 100,000/cu.mm
deep Haematocrit rise 20% or more
Abdominal pain
3 Circulatory failure: 1 of the followings 100,000/cu.mm
 Weak, rapid pulse Haematocrit rise 20% or more
 Pulse pressure < 20 mm of Hg
 Hypotension
 cold clammy skin
 restlessness
4 Profound shock with undetectable blood pressure or 100,000/cu.mm
pulse Haematocrit rise 20% or more
Investigations:
1. To confirm diagnosis:
Days Post onset of symptoms Tests recommended
1 to 5 Detection of Viral protein: NS1 antigen

Day 5 onwards NS1 antigen
Dengue IgM +/-IgG
2. To look for complications: these tests help to monitor activity of the disease
CBC:
 Hb: if bleeding significant
 TC: common in viral fever
 Platelet : often monitoring required on a regular basis- frequency depends on the trend of platelet count
 Hct:↑ indicates hemoconcentration (due to dehydration from plasma leakage)
16
can be due to
 Correction of dehydration with fluid
 Bleeding
Hct: often monitoring required on a regular basis- frequency depends on the trend
Biochemistry: Required in selected patients if complications arise
 Urea/Cr: Impaired due to dehydration
 Na/K: dyselectrolytemia due to dehydration
 LFT: abnormal in complicated cases(nonspecific hepatitis)
 ABG: Metabolic acidosis in complicated cases
CxR: effusion
USG abdomen: Ascites
Treatment:
A: Admit if
A: Airway- Intubate if needs to be ventilated
B: Bed rest till symptomatic recovery occurs
B: Blood parameter montoring: Hct, platelet- frequency depends on the trend
B: Breathing: Ventilate if ARDS
B: Bed sore prevention for patients who are comatose
C: Circulation: Adequate Fluid/Hydration is the cornerstone of management
Oral fluid only for patients without any symptoms/signs of fluid deficit
IV fluid: for Hypovolemic patients: Amount/rate of administration/duration depends on clinical status
C: Catheterise if urine output monitoring becomes essential
C: Complication: monitor closely and treat if develops
 ARDS: Intubate & Ventilate
 Acidosis: IV NaHCO3 in severe acidosis (pH < 7.1)
 Bleeding: Blood transfusion +/- Platelet transfusion
 Coagulopathy: Thrombocytopenia: Platelet transfusion only if bleeding or platelet count <10,000/cmm
 DIC: FFP transfusion
 Dysfunction of Organs: AKI: Dialysis(if required) ALI: supportive Rx
D: Diet: Nutritious diet
D: Drugs: ● Antipyretic: Paracetamol ● Analgesic: NSAIDS for severe pain ● Antiemetic:
Domperidone/Ondensetron
D: DVT prophylaxis for immobile/bedbound patients
E: Eligible for Discharge when
 Afebrile for at least 24 hours without antipyretic
 Appetite returning
 Atleast 2- 3 days after recovery from shock
 Blood: Platelet count > 50,000/ cumm and trend is upwards
 Clinical improvement obvious
F: Fluid therapy: Start with Crystalloid- Isotonic Saline/Ringer Lactate
17
DHF Grades I & II DHF Grades III & IV
Initiate IV NaCl 6 ml/kg/hr for 1-2 hrs
Improvement No Improvement
3 ml/kg/hr for next 12- 24 hours 10 ml/kg/h for 2 hrs No Improvement IV NaCl 10- 20 ml/kg/hr for 1-2 hrs
Improvement Improvement Improvement No Improvement
discontinue IV after 24 hrs 6 ml/kg/ hr then 10 ml/kg/hr 1.Colloid or plasma 10ml/kg/hr

3 ml/kg/hr then 6 ml/kg/hr 2.Blood transfusion if bleeding
then 3 ml/kg/hr
discontinue after 24-48 hrs discontinue after 24-48 hrs Improvement
10 ml/kg/hr then
6 ml/kg/hr then
3 ml/kg/hr
discontinue after 24-48 hrs

Improvement = Haematocrit falls, pulse rate and blood pressure stable, urine output rises
No Improvement = Haematocrit or pulse rate rises, pulse pressure < 20 mmHg, Urine output falls
Fluid therapy: Model 2!!...if you don’t want to tax your brain toooo much!!
Princicple: Rate+ amount+ duration of fluid therapy depends on pt’s clinical status
Fluid of choice: Isotonic Saline/ Ringer Lactate
Rate: Depending on hemodynamic status+ Urine output + periodic Hct results there are 4 standard regimes:
20 ml/kg/hr
10 ml/kg/hr switch between different regimes on the basis regular monitoring
6 ml/kg/hr of above parameters
3 ml/kg/hr
Additionally: Some patients may need:
 Colloid in case of refractory shock not responding to Crystalloid
 Blood transfusion in case of significant bleeding respectively
18
TB
Causative organism: Mycobacterium tuberculosis
Mode of transmission: Transmission occurs when a person inhales droplet nuclei containing M. tuberculosis, and the
droplet nuclei traverse the mouth or nasal passages, upper respiratory tract, and bronchi to reach lungs
Pathogenesis
Infected person
droplets
Susceptible host
Lungs: primary infection
Subpleural focus bacilli Regional spread: lymph nodes

(Ghon focus)
Dead Dormant (Live) Multiplication (progressive primary disease)

Lungs
Latent infection (LTBI) Extrapulmonary
Disseminated disease
Reactivation or reinfection (secondary/post primary TB)
Lungs
Extrapulmonary
Disseminated disease
 Appetite loss  Chill (+/- Rigor)
 Acute febrile illness  Decreased
 Appetite loss  Energy loss
Symptoms: Signs:
 Cough
 Chest pain
 Hemoptysis
Pleural: 1. f/o Pl. effusion GU
Pericardial: 1.f/o Pericarditis 2. f/o Pericardial effusion 1.f/o Pelvic Inflammatory disease
Neurological: 1. f/o Meningitis 2. f/o Tuberculoma 2.f/o Urethritis/Epidymitis
3.Renal TB: Sterile Pyuria (Urinary WBCs++ but
Adrenal: 1. f/o Adrenocortical insufficiency
\
Culture negative)
Lymph Nodes: Lymphadenopathy
Skeletal: Bone/Joint TB
1.Superficial: typically palpable +/- tender node(s)
1.f/o Osteomyeltis
2.Deep lymph nodes: Mediastinal/hilar/intra-abdominal
2.Vertbral TB: may lead to compressive Myelopathy
enlarged node(s): mostly radiologically evident
Abdominal Active3.Peritoneal:
pulmonaryAscites
disease is NOT a prerequisite for any
1.f/o Colitis Extrapulmonary TB
2.f/o Intestinal obstruction (due to fibrotic stensosis)
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Investigations
1. Microbiological diagnosis: Confirmation of the disease-
 Demonstration of AFB
 XpertTB/RIF assay: detects M. TB DNA + Rifampicin resistance( which is a predictor of INH resistance)
Samples for these tests are taken from the affected site/organ-
Pulmonary TB- Extrapulmonary-
Sputum: spontaneous/induced Pleural- Pleural fluid/ Pleural biopsy
Bronchoscopic washing/lavage Meningeal TB- CSF
Lung biopsy Pericardial- Pericardial fluid
Lymph nodes- Biopsy
Peritoneal- Ascitic fluid/Peritoneal Biopsy
GU- urine/Vaginal swab
1. Radiological- Xray/CT findings 3. Biochemical marker- High ADA (Pleural fluid/Pericardial fluid/CSF)
2. Histopathological- Biopsy sample showing caseating granulomatous inflammatory changes
4. Mantoux test- DOES NOT confirm TB, SUGGESTS exposure to TB bacilli

Treatment: daily regime
Pulmonary TB (Non- drug resitant/Drug sensitive cases)

Type of cases Intensive phase(IP) Continuation phase(CP)
New cases: 2 months: HRZE 4 months: HRE H: Isoniazid
R: Rifampicin
Previously treated cases: 2 months: HRZES E: Ethambutol
followed by 5 months: HRE Z: Pyrazinamide
1 month: HRZE S: Streptomycin (IM
Extrapulmonary TB: ALL extrapulmonary same as Pulmonary TB EXCEPT

CNS TB
Skeletal TB IP same; CP: is extended by ANOTHER 3-6 months depending on clinical response
Disseminated TB So IP 2 months; CP 7-10 months
Total duration of Treatment
Pulmonary TB & ALL extrapulmonary TB EXCEPT CNS TB / Skeletal TB/ Disseminated TB: 6 months
CNS TB / Skeletal TB/ Disseminated TB: 9-12 months
Additional drugs:
1. Vitamin B6: throughout the ENTIRE duration of ATD therapy to prevent INH induced Peripheral neuropathy
resulting from B6 depletion
2. Corticosteroid for 6- 8 weeks depending on clinical response in cases of
 CNS TB
 Pericardial TB
Monitoring:
LFT: Pretreatment and thereafter periodically if hepatitis develops
Microbiological: 1 sputum specimen at the completion of IP and 1 at the end of the treatment
Body weight: monthly
Chest x ray: if required (as per clinical scenario)
Extrapulmonary TB: Treatment response is best assessed clinically, help of radiological or any other relevant
investigations can be taken based on clinical judgement.
20
Classification and side effects of ATDs
WHO grouping
Group 1: First Line Oral Agents -RHEZ
Rifampicin: (R) INH: (H)
Hepatotoxicity Peripheral neuropathy
Immunological reactions: Hepatitis
 Agranulocytosis Lupus like syndrome
 Thrombocytopenia Pyrazinamide: (Z)
 Leukopenia Hepatotoxicity
 Acute interstitial nephritis Hyperuricemia +/- Acute gouty arthritis
Exanthem Exanthem
Orange urine Ethambutol: (E) Retro bulbar neuritis
For Drug resistance cases only- traditionally following are called 2nd line ATDs
Group 2: Injectables: Kanamycin/Amikacin/Capreomycin/Streptomycin (S) - Ototoxity and Nephrotoxicity
Group 3: FQs: Levofloxacin; Moxifloxacin; Ofloxacin
Group 4: Para-Aminosalicylic Acid; Cycloserine; Ethionamide
Group 5 TB drugs: limited data on efficacy and/or long term safety
Clofazimine/Linezolid/ (Amoxicillin+ Clavulanate)/Thioacetazone/ (Imipenem+Cilastatin)/(Meropenem+
Clvulanate)/High Dose Isoniazid/ Clarithromycin/ Bedaquiline
Ongoing Clinical trial Pretomanid; Delamanid
Bedaquiline
The only new medicine/molecule discovered in more than forty years for TB.
It is a Diarylquinoline anti mycobacterial drug indicated as part of combination therapy in adults with MDR-TB
when an effective treatment regimen cannot otherwise be provided. It should be administered by DOTS.
The WHO Expert Groups recommendation,
It may be added to a WHO-recommended regimen in adult MDR-TB patients in following circumstances:
• When an effective treatment regimen containing four second-line drugs in addition to Pyrazinamide
according to WHO recommendations cannot be designed
• When there is documented evidence of resistance to any FQ in addition to multidrug resistance.
MOA: Bedaquiline affects the proton pump for ATP synthase.
S/E
Nausea
Joint
Chest pain
Headache
Arrhythmias may induced by prolonged QT
MDR TB
MDR-TB is defined as TB bacilli resistance to INH and Rifampicin with or without resistance to other ATDs.
(Based on DST results from an RNTCP accredited laboratory.)
MDR-TB Suspect can be any of the following:
• Any TB patient who fails an RNTCP Category I or III treatment regimen
• Any RNTCP Category II patient who is sputum smear positive at the end of the fourth month of treatment or later
• Close contacts of MDR-TB patients who are found to have smear positive pulmonary TB (PTB) disease
C/F- depends on site of TB
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 Appetite loss
 Acute febrile illness
 Cachexia
 Decreased energy level
Symptoms: Signs:
 Cough
 Chest pain
 Hemoptyis
Pleural f/o Pl. effusion
Pericardial:
1. f/o Pericarditis
2. f/o pericardial effusion -
Neurological
1. f/o TB Meningitis
2. f/o Tubeculoma
Lymph Nodes TB Lymphadenotahy
1. Superficial: typically palpable (+/- tender) cervical node(s)
2. Deep lymph nodes: Mediastinal/hilar/intra-abdominal enlarged node(s): mostly radiologically evident
Abdominal
1. f/o Colitis
2. Intestinal obstruction
3. Peritoneal: Acites
GU
1. f/o PID
2. f/o urethritis/epidymitis/prosititis
3. Renal: Sterile pyuria( WBCs++ but no organism/culture negative)
Skeletal- Bone TB:
1. f/o Osteomyelitis
2. If vertebral: f/o compressive myelopathy
Adrenal: f/o Adrenocorical insuffiency
Investigations:
1.Microbiological diagnosis-
 AFB
 XpertTB/RIF assay: detects Myco. tb DNA+ Rifampicin resistance( which is a predictor of INH
resistance)
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Samples for these tests are taken from the affected site/organ-
Extrapulmonary-
Pulmonary TB- Pleural- Pleural fluid/ Pleural biopsy
Sputum Meningeal TB- CSF
Bronchoscopic washing/lavage Pericardial- Pericardial fluid
Lung biopsy Lymph nodes- Biopsy
Peritoneal- Ascitic fluid/Peritoneal Biopsy
GU- urine/Vaginal swab
1. Radiological- Xray/CT
2. Histopathological- Biopsy sample showing caseating granulomatous inflammatory changes
3. Biochemical marker- ADA
4. Mantoux test- DOES NOT confirm TB, SUGGESTS exposure to TB bacilli
Treatment- called Cat IV regimen
6 drugs for 6 - 9 months (Intensive phase)
Kanamycin + Ofloxacin/Levofloxacin + Ethionamide + Pyrazinamide + Ethambutol + Cycloserine
4 drugs for atleast 18 months (Continuation phase)
Ofloxacin/Levofloxacin + Ethionamide + Ethambutol + Cycloserine
Extensively Drug resistance TBXDR-TB
XDR-TB = resistance to Isoniazid and Rifampicin (i.e MDR) + resistance to any of the FQs and to at least one of
injectable second-line drugs (Amikacin/Capreomycin/Kanamycin)
• Use Pyrazinamide and any other Group 1 agent that may be effective.
• Use an injectable agent to which the strain is susceptible and consider an extended duration of use (12 months or
possibly the whole treatment).
• Use a higher-generation fluoroquinolone such as Moxifloxacin/Gatifloxacin.
• Use all Group 4 agents that have not been used extensively in a previous regimen or any that are likely to be
effective.
• Add two or more Group 5 drugs (consider adding Bedaquiline or Delamanid)
• Consider adding a new investigational drug eligible for use under the compassionate use scheme if policy of the
WHO endorses its use for XDR-TB.
• Consider high-dose isoniazid treatment if low-level resistance or absence of the katG gene is documented.
X-DR Regimen design- at least six drugs were used in the intensive phase and four in the continuation phase
IP: 6-12 months:
Capreomycin+ Para-Aminosalicyclic acid+ Moxifloxacin+ High dose INH+ Clofazimine+ Linezolid+ Co-amoxiclav
CP: 18 months: Para-Aminosalicyclic acid+ Moxifloxacin+ High dose INH+ Clofazimine+ Linezolid+ Co-amoxiclav
“Options are limited and there is no expert consensus on a specific regimen that would be best for X-DR
patients”- WHO
23
Manotux test
It’s a test which is indicative of the presence of cell mediated immunity (CMI) against Mycobacterium- technically
meaning that the person has had prior sensitization with mycobacterial antigen, either of M. tuberculosis or of
another cross reacting mycobacterium.
Method:
0.1 ml of PPD is injected strictly intradermally on the volar aspect of the forearm
Area observed for any INDURATION after 48 to 72 hours
Redness (but no induration) Induration
Size: diameter perpendicular to the long axis

Negative
Interpretation to be done keeping patient profile in mind
Interpretation: Induraton is indicative of the presence of cell mediated immunity (CMI) of the delayed
hypersensitivity type. Technically, this means that the person has had prior sensitization with mycobacterial antigen,
either of M. tuberculosis or of another cross reacting mycobacterium. In other words a result of 5 mm and above of
induration is positive for CMI, strictly from immunological view point.
The Mantoux test does not measure immunity to TB but the degree of hypersensitivity to tuberculin. There is no
correlation between the size of induration and likelihood of current active TB disease.The test has a poor positive
predictive value for current active disease.
The results of this test must be interpreted carefully. The person's medical risk factors determine the size of
induration considered to be positive
≥5 mm is considered to be positive in
HIV-positive person
Recent contacts of active TB cases
Persons with nodular or fibrotic changes on Chest X-ray consistent with old healed TB
Severely immunocompromised persons: eg. a. Organ transplant recipients b. Pts. on cytotoxic/immunosuppressives
≥10 mm is considered to be positive in
Recent arrivals from high-prevalence countries
Persons with lots of medical comorbidities
Children less than four years of age
Health care professionals
≥15 mm is positive in
Persons with no known risk factors for TB. Reactions larger than 15 mm are unlikely to be due to previous BCG
vaccination or exposure to environmental mycobacteria.
False-positive result: Some persons may react to the TST even though they are not infected with M. tuberculosis. The
causes of these false-positive reactions may include, but are not limited to, the following:
1. Infection with non tuberculous mycobacteria
2. Previous BCG vaccination
False-negative result: A negative Mantoux result usually signifies that the individual has never been exposed to M.
tuberculosis. However, there are factors that may cause a false-negative result or diminished ability to respond to
tuberculin.
1. Cutaneous anergy ( inability to react to skin tests because of a weakened immune system)
2. Very young age (less than six months old)
3. Recent live-virus vaccination (e.g., measles vaccine)
4. Overwhelming TB disease
5. Incorrect method of TST administration/Incorrect interpretation/insufficient dose
24
Gastrointestinal System
Gastro-esophageal reflux disease (GERD)
Condition characterized by reflux of gastric acid content into the esophagus.
Pathophysiology: Following factors play important roles:
1. Lower esophageal sphincter (LES) dysfunction: most important risk factor
2. Hiatus hernia
3. Delayed esophageal emptying
Clinical features:
1. Heartburn: Typically aggravates on: Lying flat after meals; in some pts after alcohol ingestion.
2. A bitter/ sour test in the mouth due to regurgitation of gastric acid.
3. Atypical/ extra‐esophageal manifestation:
a. Chronic cough
b. Hoarseness of voce………………..( Remember ENT days!!!....Reinke’s edema- vocal cord swelling)
c. Non‐cardiac chest pain
Investigation
1. Upper GI endoscopy: Typically shows: reflux esophagitis
2. Esophageal manometry with pH estimation
Treatment
1. Lifestyle modification:
I. Stay upright for approx. half an hour after each meal
II. To raise the head end of the bed during night
2. Medications: H2 blockers/ PPI
Complication: Barrett’s esophagus
Barrett’s esophagus
It is condition where esophageal squamous epithelium is replaced by metaplastic columnar epithelium.
Risk factor: Long standing GERD
Clinical features: Barrett’s itself is usually asymptomatic, long standing symptoms of GERD: Present.
Investigation
1. Upper GI endoscopy: Shows orange, velvety gastric type epithelium in the esophagus
2. Confirmation of diagnosis by mucosal biopsy.
Treatment
1. Medications to treat GERD
2. Endoscopic surveillance:
Complication: Esophageal adenocarcinoma.

Gastroduodenal diseases
Gastritis/ Duodenitis Gastric/ Duodenal ulcer (Peptic ulcer)
Mucosal inflammation only Breach in the continuity of mucosa
Gastric or Duodenal: ANATOMICALLY They are different BUT for all practical purpose they are “same”!!!
“Itis” or “Ulcer”: PATHOLOGICALLY They are different BUT for all practical purpose they are “same”!!!
Therefore Gastroduodenal pathology includes ALL of these…..
So…GASTRITIS/DUODENITIS/GASTRIC ULCER/DUODENAL ULCER/PEPTIC ULCER
Don’t expect me to “copy+ paste” same answer 5 times!!!
Etiology/ Risk factors:
1. Chronic H.pylori infection Alternative way
2. Non- H.pylori causes 1. Benign etiology 2. Malignancy
 Drugs: NSAIDs/ Steroids Chronic H.pylori infection
 Stress ulcer: Can occur in any critically ill patients Drugs: NSAIDs/ Steroids
 Portal Hypertensive Gastropathy Stress ulcer: Can occur in any critically ill patients
 Malignancy Portal Hypertensive Gastropathy
Clinical features: Any ≥ 1 of the followings
Abdominal Pain:
 Typically epigastric
Acute epigastric pain: Think about-
 Variable duration
Acute ●Gastroduodenal pathology ●Pancreatitis ●Cholecystitis
 Often occurs periodically
 Nature: Dull aching pain/burning
 Aggravating and relieving factors: variable‐ in some food aggravates pain whereas in some empty stomach
aggravates pain
 Radiation to the back should raise the suspicion of:
a. Perforation
b. Pancreatitis
Associated symptoms:
a. Heartburn/ feeling of indigestion
b. Water brush: Regurgitation of bitter/ sour contents with sudden salivation
c. Features usually absent in benign ulcer:
I. Significant vomiting
II. Weight loss However these are not ALWAYS present in malignant ulcer
III. Appetite loss
Anaemia related manifestation: particularly occult bleeders
Bleed‐ Bleeding may be overt or occult Upper GI bleed: Think about: ●Gastroduodenal pathology ●Variceal
Overt bleeding: Hematemesis and/ or Melena……
 Blood loss may be mild/ moderate/ massive enough to make the patient’s hemodynamics unstable
 In hematemesis, the colour of blood may be fresh/ altered red coloured depending on the time elapsed between
onset of bleeding and vomiting.
 PR examination reveals melena in stool
Occult bleeding: these patients often present with Anaemia related manifestation with or without Abdominal
pain/associated symptoms Anaemia with NO OBVIOUS GI bleed: still ALWAYS Think about!
Collapse: due to massive GI bleed ●Occult Gastroduodenal disease ●Occult Portal Hypertensive Gastropathy
Drug history: H/O intake of an “offending” drug MAY BE present‐ NSAID(“pain killers”)/ Steroid
(Don’t forget Aspirin…it’s an NSAID!! but because it’s principal use is for thrombosis prevention (antiplatelet effect) often
patients describe this as “heart or brain medicine” rather than painkiller )
Sign: Any ≥ 1 of the followings
Anaemia
BP: hypotension if massive bleed:
Circulatory disturbance: if massive bleed: tachycardia/weak pulse
“Digital” examination PR examination reveals melena in stool
Epigastrium
 Tenderness: may be present
 Lump: if present is highly suspicious of malignancy
Investigations
A.Blood:
1. Hb, TC, DC, CRP: Hb MAY BE low depending on the amount of blood lost
2. If no OVERT bleeding but iron deficiency anemia is suspected:
 Serum iron studies:Iron/Ferritin/Transferrin saturation
3. Renal function: Na+ K+ Urea Creatinine
4. Lipase ± Amylase: To rule out acute pancreatitis
5. Clotting profile: Platelet count, BT, CT, PT, aPTT, INR (if active/Overt bleeding)
B.Faecal occult blood test (FOBT)
C.Upper GI Endoscopy:
a. Confirms presence of ulcer/inflammation & their exact anatomical location
b. Helps to confirm atleast 2 of the common etiologies:
 Endoscopic Biopsy confirms histopathological nature of the ulcer‐ benign/malignant
 Diagnosis of H.pylori infection: Rapid urease test
Treatment
Gastroduodenopathy….”itis”/ulcer
Supportive treatment Definitive treatment
Required for GI BLEED Etiological treatment
Supportive treatment: for those with significant GI bleed: ≥1 of the followings

A. Admit if ongoing bleeding or significant bleeding
Airway: To be protected particularly if there is risk of aspiration
B. Breathing: Oxygen
Bowel rest: Nil by mouth till bleeding is under control, nasogastric suction
C. Circulation:
I. IV fluid resuscitation followed by maintenance fluid: Ringer lactate/ Normal saline
II. Blood transfusion
D. Drugs: Infusion of PPI: Pantoprazole for at least 48 hours
E. Endoscopy:
I. Urgent endoscopy: to confirm the diagnosis
II. Endoscopic interventional therapy to ARREST BLEEDING
 Injection therapy: solutions of diluted epinephrine
 Thermal coagulation
Etiological treatment: for bleeders as well as non-bleeders
H.pylori +Ve H.pylori –Ve:
Eradication of H. pylori: “Triple therapy”= 2 antibiotics + PPI PPI for at least 4‐6 weeks
Standard regime: Amoxicillin+ Clarithromycin + any PPI: for 14 days Stop any offending drug‐ NSAID/Steroid
Followed by
Any PPI for atleast another 4‐6 weeks
Diagnosis of H.pylori infection:………(NOT a “must read” topic!!)
a. Endoscopically: Rapid urease test (RUT)
RUT / CLO test (Campylobacter‐Like Organism), is a rapid diagnostic test for diagnosis of Helicobacter pylori.
The basis of the test is the ability of H. pylori to secrete the urease enzyme, which catalyzes the conversion of Urea to
NH3 & CO2. The test is performed at the time of Endoscopy. A biopsy of mucosa is taken from the stomach/duodenum,
and is placed into a medium containing urea and an indicator such as phenol red. The urease produced by H.
pylori hydrolyzes urea to ammonia, which raises the pH of the medium, and changes the color of the specimen from
yellow (NEGATIVE) to red (POSITIVE).
b. Non-endoscopically: 1. Urea breath test 2. H.pylori fecal antigen 3. Blood serology for H pylori
Acute Pancreatitis
Acute inflammation of pancreas.
Causes:
1. Alcohol Autoimmune diseases Abdominal trauma
2. Biliary disease: Gall stone
3. ↑↑Calcium 1 & 2‐ COMMONEST causes
4. Cystic Fibrosis
5. Dyslipidemia: Hypertriglyceridemia
6. Drug induced: steroid/ Valproate/Thiazides
7. ERCP‐ complication of ERCP
Signs and symptoms: 1. Due to Pancreatitis itself 2. Due to complications, IF any
System Symptoms Signs
Abdomen Onset: Sudden/Rapidly developing 1.Epigastric Lump
Site: Epigastrium  Pseudocyst/Pancreatic Phlegmon
2.Signs of paralytic ileus
Character: Deep seated/dull may be excruciating
PAIN (NOT a Burning pain/ Cramp)  Abdominal distension
Radiation: To the back but NOT ALWAYS  Reduced bowel sound
May Aggravate on: Supine position/Postprandial3.Signs of peritonitis
May Relieved by: Stooping forwards with trunk  Guarding/Rigidity
flexed and knees drawn up Cullen sign: hemorrhagic discoloration of the
(aggravation/relief: MAY not occur) umbilical area due to intraperitoneal hemorrhage
Associated with Grey Turner: hemorrhagic discoloration of the
left flank associated with acute hemorrhagic
Severe nausea ± retching ± vomiting
pancreatitis.
Features due to Complications- may be develop rapidly within few hrs - days
Breathing ARDS: SOB Tachypnoea; ↓SpO2; Bilateral crepitations
Circulation Altered sensorium BP: Hypotension

Dry skin/mucous membrane CRT‐ prolonged
Decreased Urine output Extremity: Tachycardia/ Weak pulse
Dermal Erythematous skin lesion due to subcutaneous fat
necrosis
Eye Eye: Jaundice may be present Icterus may be present
Mechanism: Inflammation of the head of
pancreas may lead to CBD obstruction.
Fever
Acute epigastric pain: Think about- Acute ●Gastroduodenal pathology ●Pancreatitis ●Cholecystitis ●Hepatitis
Acute epigastric pain with Circulatory compromise( “Shock”/ “Collapse”/”hemodynamically unstable”)
Think about- Acute ●Gastroduodenal pathology ●Pancreatitis
(shock due to bleed) (shock due to 3rd spacing)
Investigations
1. To confirm the diagnosis of acute pancreatitis 2. To detect risk factors and complications of acute pancreatitis
1. Blood:
1.Hb, TC, DC CRP
 Hb: ↓ in hemorrhagic pancreatitis
 TC, DC, CRP: ↑inflammation or intra‐abdominal infection‐ Necrotizing pancreatitis, Peri pancreatic abscess
2.Renal function: Na+/ K+/ Urea/Creatinine (To look for any dehydration)
3.LFT: Mild derangement due to “nonspecific” hepatitis:
4.Pancreatic enzymes: Amylase or Lipase levels at least 3 times above the reference range are considered diagnostic
of acute pancreatitis.
However, there are other Intra as well as Extra-abdominal causes of elevation of serum Amylase. Lipase is more
PANCREAS SPECIFIC & has a longer half‐life, so it’s MORE useful if there is a delay between the onset of pain and
the time the patient seeks medical attention.
Elevated lipase levels are more specific for pancreas than elevated amylase levels.
The level of serum amylase or lipase does not indicate whether the disease is mild, moderate, or severe
5.ABG: To look for: Metabolic acidosis/ ↓pO2.
6.Ca level:
 Hypercalcemia is a risk factor of acute pancreatitis
 Acute pancreatitis leads to hypocalcaemia (by saponification of fat)
7.Fasting lipid profile
2. Chest X Ray: To look for: ARDS/Pleural effusion.
3. USG abdomen: 4. CECT abdomen:
To look for: To look particularly for:
 Inflammation of pancreas  Necrotizing pancreatitis
 Gallbladder stone  Peripancreatic abscess
 CBD dilatation  Pancreatic pseudocyst
 Ascites
5. Aspiration of ascitic and pleural fluid: Show elevated levels of amylase and lipase.
Treatment
Acute Pancreatitis
Supportive: Medical Management Interventional treatment Treat/Remove etiology
Basic supportive Organ support Non surgical Surgical

(if Multi-organ failure) (for Loco-regional complication)
Supportive treatment
A. Absolute bed rest till condition stabilizes
B. Breathing: Ventilator‐ for ARDS
B. Bowel rest:
 Nil by mouth initially till clinical improvement starts
 Ryle’s tube suction (if required)
 Gradual introduction of enteral feeding
 If required: Total Parenteral Nutrition
C. Maintain circulation:IV fluid : amount + rate + duration depends on clinical status‐ Bolus +/‐ maintenance
C. Catheterisation: To monitor urine output: if circulatory disturbance/Renal failure is present
D. Drugs (Supportive):
 Analgesic‐antispasmodic:  Antibiotics (particularly if intra‐abdominal
Drotaverine infection is suspected): Imipenem
Opioids: Tramadol/ Pethidine  Antifungal (if intra‐abdominal fungal infection)
Avoid morphine as it constricts sphincter of OD  Anti‐ulcer drugs: To avoid stress ulcer: PPI
D. Diet: Gradual introduction of normal diet: Initially clear liquid; then semisolid/soft diet; then normal diet
D. DVT prophylaxis till immobile
E. External Intervention
 Interventional treatment
A. Percutaneous drainage of peripancreatic abscess/ infected pseudocyst
B. ascites/ pleural effusion‐ rarely significant in amount requiring drainage
 Surgical treatment
A. Necrosectomy/ debridement in necrotizing pancreatitis
E. Etiological treatment: treat/address the etiology…eg.
 Early cholecystectomy in case of gallstone pancreatitis
 STOP alcohol
 STOP the offending drug
Complications of acute pancreatitis‐ ‘’PANCREAS’’
Organ Complications
Pancreatic 1. Necrosis
2. Hemorrhage
3. Pancreatic pseudocyst (sterile/ infected)
4. Peripancreatic abscess
Abdomen 1. Ascites
2. Paralytic ileus
3. Peritonitis
Neurological Encephalopathy
Circulatory Circulatory shock/ collapse
Respiratory 1. ARDS
2. Pleural effusion‐ It results from leakage of pancreatic fluid through small pores in the
diaphragm into the pleural cavity
Eye Purtscher’s retinopathy (Sudden blindness due to vaso‐occlusive and Hemorrhagic vasculopathy)
AKI Acute tubular necrosis (ATN) leading to AKI
Skin Subcutaneous fat necrosis
Ranson’s criteria/ score….(”For Short Note obsessed”)

A predictive score which can reasonably predict prognosis/ development of complication(s) in an acute pancreatitis.
On admission Within first 48 hours
1. Age >55 years 1. Arterial PO2 < 60 mm Hg 4. Ca++ <8 mg/dL
2. WBC count > 16000/cu.mm 2. BUN value increases by > 5 mg/dL 5. Drop in hematocrit: >10%
3. Blood glucose >200 mg/dl (BUN/2.8) = Urea 6. Estimated fluid deficit >6L
4. AST >250 U/L 3. Base deficit >4 mEq/L
5. Serum LDH >350 U/L
Presence of ≥3 of the above Presence of ≥1 of the above predicts worse prognosis
predicts a complicated course
Hyperamylasemia……..(for Short note “obsessive lovers”)
1. Abdominal causes: 2. Extra ‐abdominal causes:
 Acute/ chronic pancreatitis  Salivary gland diseases: Mumps/
 Perforation: Bowel/ peptic Sialolithiasis (stone)/ tumor
 Bowel infarction  Bronchogenic carcinoma
 Acute cholecystitis  Ovarian carcinoma
 Ectopic pregnancy (ruptured)
Malabsorption syndrome
A group of disorders characterized by impaired absorption of different food particles and nutrients.
Examples/Causes/Types:
1. Bacterial overgrowth syndrome 4. Crohn’s Disease
2. Short bowel syndrome (post‐resection): 5. Dietary Intolerance: Lactose Intolerance/
Terminal ileum/Extensive small intestinal resection 6. Enteropathy: Protein losing enteropathy
3. Celiac disease
Mechanism of clinical manifestations and clinical features:
1. Due to Malabsorption of different nutrients: ≥ 1 OF THESE
2. “Unique” feature(s) of the disease: some of them, apart from malabsorption, cause OTHER manifestations
Substances malabsorbed/deficient Clinical features
A Albumin Swelling (anasarca)
Fat Steatorrhoea
Flatulence
B Bile acids Vitamin A Night blindness
Vitamin D Osteomalacia/Osteoporosis‐ Bone pain/deformity/fracture
Vitamin E CNS manifestations
Vitamin K Coagulopathy
Vitamin B12 Anemia ± Neurological complications
C Ca++ Tetany‐ spontaneous muscle spasm/Paresthesia (perioral)
Diet (Protein + Carbohydrate + Fat) Weight loss/Weakness/Wasting
D Vitamin D Proximal myopathy/Musculoskeletal pain/Bony deformity
E Electrolytes Sodium Encephalopathy
Potassium Muscle atony‐ Constipation/Distension
F Fe++ Iron deficiency anemia
Fluid Watery diarrhea
Fat Steatorrhoea
Investigations: To look for evidence of malabsorption & to detect its consequences
Blood:
1.Hb, TC, DC, CRP, MCV: Hb: ↓ (in Iron deficiency/ vitamin B12 deficiency) MCV: ↓/↑ (depending on the cause).
2.Iron studies:Serum Iron/Serum Ferritin/ Serum Transferrin saturation
3. Biochemistry:Na+/K+/Ca++/Mg++/Urea, Creatinine
Clotting profile
Serum Vitamin B12 level + Folate level+ Vit D3 level
Serum Albumin
4.Tests to confirm Malabsorption:
Fecal fat content: ↑
D‐Xylose test
5.Tests to confirm the underlying disease: Intestinal mucosal biopsy: Often confirm the diagnosis in some of the cases.
Treatment:
1.General treatment
1. Nutritional support‐ Dieatary +/‐ fluid replenishment
2. Supplementation of vitamins and minerals
2.Specific treatment- depends on the underlying disease
Inflammatory bowel disease (IBD)

It is a condition characterized by widespread inflammatory damage to different parts of small and large intestine.
The pattern of inflammation and subsequent clinical features lead to 2 distinct clinical entities:
1. Crohn’s disease 2. Ulcerative colitis.
Crohn’s disease
Characterized by relapsing and remitting segmental/ patchy inflammation of intestine.
Sites (according to descending order of frequency):
1. Terminal ileum and proximal ascending colon: Ileocolitis
2. Terminal ileum: Ileitis
3. Large gut: Colitis‐ however, involvement of sigmoid colon and rectum is extremely rare and this variety is
usually associated with perianal manifestations.
Clinical features:
Mechanism of clinical manifestations: Manifestations can be chronic/rapid/acute on chronic‐ they may come back after
a quiscent stage when the disease flares up
Extra-intestinal features
Clinical features of ileocolitis:

1. Due to chronic inflammation:
1. Pain abdomen: Often in right iliac fossa 4. RIF‐tenderness / mass may be present
2. Diarrhea Usually watery, rarely bloody (matted intestine + lymph nodes + mesentery)
3. Fever, loss of appetite and weight loss 5. F/O Malabsorption syndro
2. Due to intestinal obstruction (fibrostenotic occlusion of intestine): Acute/Subacute
1. Abdominal pain 4. Distension
2. Borborygmi/Bloating 5. Emesis (Vomiting)
3. Constipation 6. Feces/Flatus
3. Due to fistulisation:
1. Enterocolic fistula: Malabsorption 3. Enterovaginal fistula: Feculent per‐vaginal
2. Enterovesicle fistula: Feculent urine discharge
4. Enteromesenteric fistula: Intra‐abdominal abscess
Clinical features of perianal disease:
1. Perianal fistula 3. Visible anal skin tag
2. Perianal abscess 4. Anal fissure
The disease classically relapses and remits.
Investigation
1.Blood: Hb, TC, DC, CRP/ESR‐ TC, DC, CRP, ESR: ↑ due to inflammation/ intra‐abdominal infection
Hb: ↓ due to: Chronic inflammation/ Iron deficiency/ B12 deficiency
2.Renal function: Na+ K+ Urea Creatinine
3.If malabsorption is suspected: Albumin, Serum Ca++, Vitamin B12, Vitamin D, Iron studies
4.Stool: Look for ova/ parasites/ cysts. Fecal Calprotectin level: High( “Inflammatory marker” of Intestine)
5.Colonoscopy: shows mucosal inflammation/ ulceration with skip areas. Colonoscopic biopsy confirm the diagnosis.
6.CECT abdomen: To visualize the intestine for any obvious anatomical abnormality/ distortion(stricture/fistula)
Supportive treatment: ≥1 relevant if patient is very sick

1. Admit‐ if severe diarrhea/volume depletion
2. Bowel rest‐ NPM till clinically improved
3. Circulation‐ IV fluid in severe diarrhea‐ Bolus & maintenance depending on the clinical scenario
4. Catheterisation‐ To monitor urine output‐ if required
5. Drugs:
Analgesic/Antispasmodic: Drotaverine/ Dicyclomine.
Antidiarrhoeal: Loperamide (May cause paralytic ileus)
Antibiotic‐ often given empirically
Specific treatment:
1. Aminosalicylate: To maintain remission- No longer the first line drug, can be used as adjunct with Steroid
 Drugs: Mesalamine/Olsalazine/Balsalazide: No longer the first line drug, can be used as adjunct with Steroid
2. Corticosteroid: DOC in most CD patients to achieve remission
 Systemic corticosteroids: Prednisolone/ Methylprednisolone
3. Immunomodulators: Used in moderate to severe disease‐ To induce + to maintain remission
● Non biologics: Azathioprine/Methotrexate/Ciclosporine ● Biological agents: Infliximab/ Natalizumab
Surgery: In medically refractory cases/for complications‐ Ilectomy/Ileocolectomy
Ulcerative colitis
Characterized by relapsing and remitting inflammation of the colon which is continuous.
Common sites:
1.Sigmoid colon + rectum: Proctosigmoiditis 2.Left side of colon: Left sided colitis 3.Pancolitis
Clinical features: Manifestations can be chronic/rapid/acute on chronic‐ they may come back after a quiscent stage
when the disease flares up
Mechanism of clinical manifestations:1. Due to chronic inflammation 2. Due to toxic megacolon 3. Extra‐intestinal
1. Clinical features due to chronic inflammation:

1. Bloody/Non bloody diarrhoea
2. Hemodynamic instability ± Pallor
3. Abdo pain: LUQ/LLQ pain: continuous/ spasmodic
4. Constitutional: Fever, weight loss, loss of appetite
2. Clinical features due to toxic megacolon: Toxic megacolon, a potentially lethal condition, is a nonobstructive colonic
dilatation larger than 6cm with signs of systemic toxicity
1. Abdominal pain ± Distension
2. Abdominal tenderness
3. Sluggish bowel sound
4. Toxicity: Fever, tachycardia, flushing
Severity of UC-Helps to assess disease activity
Criteria Mild Moderate Severe

Number of stools/day <4 4‐6 >6
Weight loss (% of body weight) None 1‐10% >10%
Pulse < 90 90‐100 >100
Fever None 99‐100 ⁰F >100 ⁰F
Hematocrit (PCV) Normal 30‐40% <30%
ESR <20 mm/hr 20‐30 mm/hr >30 mm/hr
Albumin (gm/dL) Normal 3‐3.5 <3
Extra-intestinal manifestations: same for both UC & CD….(SN)

Ocular: Uveitis + Episcleritis Liver: Primary sclerosing cholangitis
Lungs: Interstitial lung disease Kidney: Nephrolithiasis
Heart: Non‐infective endocarditis Skin:Erythema nodosum; Pyoderma gangrinosum.
Abdomen: Gall stone (more common in CD) Joints: Seronegative Spondyloarthropathy; Polyarthritis
Investigation
1. Blood: Hb, TC, DC, CRP/ESR‐ Hb: ↓ due to blood loss TC, DC, CRP, ESR: ↑ inflammation/ intra‐abdominal infection
2. Renal function: Na+ K+ Urea Creatinine‐To look for dehydration
3. Serum albumin level
4. Stool: Look for ovum/ parasite/ cyst/ Gram stain, culture and sensitivity Fecal Calprotectin‐ High
5. Straight X Ray abdomen: To look for toxic megacolon (diagnosed when colonic diameter is >6 cm.)
6. Sigmoidoscopy/ Colonoscopy: Will visualize inflamed, ulcerated mucosa and biopsy confirms the diagnosis
7. CECT abdomen: To look for any structural abnormality
Treatment 1. Supportive treatment 2. Specific treatment 3. Surgical treatment
1. Supportive treatment- ≥1 relevant if patient is very sick
Admit if very sick
Bowel rest‐ nil by mouth till acute phase is over
Circulation ‐IV fluid – Bolus +/‐ Maintenance fluid depending on volume status
Blood transfusion‐ if required
Drugs: Antidiarrhoeal‐ Loperamide ( with caution, best avoided during active flare up!!)
Analgesic‐antispasmodic: Drotaverine
Antibiotic (Particularly if toxic megacolon is suspected): Cefuroxime /Pip‐Taz + Metronidazole
Emergency Rx for toxic megacolon:
1. Nil per mouth 4. Colonic decompression by: Flatus tube/ Colonoscopic
2. IV antibiotic‐ Pip‐Taz + Metronidazole 5. Surgery‐ Partial Colectomy
3. IV Hydrocortisone
2. Specific treatment
1. ASA compounds: To achieve and to maintain remission
Usually 1st line therapy in mild disease: Mesalamine/ Osalazine/ Balsalazine: PO/PR preparation
2. Corticosteroids: To achieve remission in Moderate to severe ulcerative colitis
1. Prednisolone/Methylprednisolone: PO/IV 2. Hydrocortisone: Enema/ foam
3. Immunomodulators: To achieve and to maintain remsission- Moderate to severe ulcerative colitis
Non biologics: Cyclosporine Biological agents: Infliximab
3. Surgery: Surgery is done in medically refractory cases/ for complications- Partial/ hemicolectomy
Difference between Crohn’s disease and Ulcerative colitis
Points Crohn’s disease Ulcerative colitis

Pattern of inflammation Patchy/ skip lesion Continuous
Site Ileocolitis, ileitis, colitis Proctosigmoiditis, left sided colitis, Pancolitis
Diarrhoea Not bloody Bloody
Malabsorption + -
Fistulisation + -
Perianal disease + -
Intestinal obstruction + -
Toxic megacolon - +
Irritable bowel syndrome (IBS)

Characterized by widespread GI manifestations in absence of any biochemical/ structural abnormality.
Pathogenesis: Usually the following 4 factors play important role:
1.Intestinal dysmotility 3.Enteric infection/ altered gut flora
2.Intestinal hypersensitivity to pain 4.Psychological factors
Clinical features:
1. Abdominal pain: Often lower abdominal- continuous/episodic‐Typically associated with >1 of the following:
1. Relieved after defecation
2. Change in the form/ appearance/ consistency of stool (hard / semisolid/ liquid)
3. Change in stool frequency
(Rome Criteria of IBS: Recurrent abdominal pain or discomfort at least 3 days/month in the last 3 months associated
with two or more of the ABOVE)
2. Abdominal symptoms: 4. Absent symptoms:
1. Mucoid stool 1. Nocturnal diarrhea
2. Urgency/ frequency 2. Weight loss
3. Associated manifestations: 3. Per‐rectal bleeding
1. Chest pain 4. Alternate constipation and diarrhoea
2. Palpitation
3. Pain at different sites of the body
4. Heartburn
Investigation IBS can be diagnosed from typical history, still organic diseases must be ruled out by investigations
1. Blood: Hb, TC, DC, CRP
2. Serum albumin, serum Ca++, iron studies (to rule out malabsorption)
3. Stool: OPC/ Gram stain/C.C. Faecal calprotectin: If ↑: indicates inflammatory diarrhea.
4. Colonoscopy: To rule out any structural lesion
Treatment
1. Appropriate dietary modification 6. Anti-depressants:
2. Antispasmodic: Drotaverine/Mebeverine Mechanism of action:
3. Anti-diarrheal: Loperamide a. Centrally acting pain inhibitors
4. Anti-constipation agent (Laxatives): b. Anti‐cholinergic effect.
Magnesium salts/ Poly‐ethylene‐glycol Commonly used agents are:
5. Probiotics: Lactobacillus spore
Amitriptyline/Imipramine/Fluoxetine/Paroxetine
7. Psychological counselling
Blind loop syndrome/Bacterial Overgrowth Syndrome
Blind loop syndrome occurs when part of the small intestine forms a loop that food bypasses during digestion so food
particle cannot move normally through the GIT. Slowly moving food and waste products become a breeding ground
for bacteria. So it is also called Bacterial Overgrowth Syndrome.
(Bacterial overgrowth syndrome occurs when the normally low number of bacteria that inhabit the stomach,
duodenum, jejunum, and proximal ileum significantly increases or becomes overtaken by other pathogens)
Causes- ‘’Blind loops’’ from the following may result in bacterial overgrowth syndrome:
1.Side‐to‐side or end‐to‐side anastomoses 3.Segmental dilatation of the ileum
2.Duodenal or jejunal diverticula 4.Biliopancreatic diversion
Mechanism of clinical manifestations and clinical features:

1. Due to Malabsorption of different nutrients: ≥ 1 OF THESE
Substances malabsorbed/deficient Clinical features
A Albumin Swelling (anasarca)
Fat Steatorrhoea
Flatulence
B Bile acids Vitamin A Night blindness
Vitamin D Osteomalacia/Osteoporosis‐ Bone pain/deformity/fracture
Vitamin E CNS manifestations
Vitamin K Coagulopathy
Vitamin B12 Anemia ± Neurological complications
C Ca++ Tetany‐ spontaneous muscle spasm/Paresthesia (perioral)
Diet (Protein + Carbohydrate + Fat) Weight loss/Weakness/Wasting
D Vitamin D Proximal myopathy/Musculoskeletal pain/Bony deformity
E Electrolytes Sodium Encephalopathy
Potassium Muscle atony‐ Constipation/Distension
F Fe++ Iron deficiency anemia
Fluid Watery diarrhea
Fat Steatorrhoea
2. “Unique” feature(s) of the disease: apart from malabsorption, cause OTHER manifestations
 h/o abdominal surgery‐ often present
Investigaton: Abdominal x‐ray/Abdominal CT scan/Contrast enema study
Treatment
Medical- Antibiotic‐ Tetracycline/ Rifaximin
Surgical- Repair of the defect and blind loop
Replenish‐ deficient nutrients
Celiac disease
Celiac disease (gluten‐sensitive enteropathy), is a chronic disorder of the GIT that results in an inability to tolerate
gliadin‐the alcohol‐soluble fraction of gluten.
Gluten is a protein commonly found in wheat, rye, and barley. When patients with celiac disease ingest gliadin, an
immunologically mediated inflammatory response occurs that damages the mucosa of their intestines, resulting in
maldigestion and malabsorption of food nutrients.
Symptoms & Signs
1. Due to Malabsorption of different nutrients: ≥ 1 OF THESE…see above!!
 Endocrinopathy‐a.Amenorrhea b.Delayed menarche c.Impotence/Infertility
 Dermatitis herpetiformis‐ pruritic, papulovesicular lesions on the extensor surfaces of the extremities, trunk
Investigations
1.Blood
Electrolytes and chemistries – Albumin, Urea, Creatinine, Na, K, Ca, Clotting profile
Hematologic tests – Hb, Iron study, Vit B12/Folate
Confirmatory test: Serum IgA antibodies- Anti-tissue transglutaminase antibody (IgA TTG)
2.Stool examination –Increased Fat content due to Fat malabsorption
3.Endoscopy and biopsy- Duodenal biopsy‐ villous atrophy + Total mucosal hypoplasia
Management: Removal of gluten from the diet is essential
Whipple disease
Whipple disease is a systemic disease caused by a gram positive bacterium Tropheryma whippelii.
C/F
Symptoms & Signs
3. Due to Malabsorption of different nutrients: ≥ 1 OF THESE…see above!!
 CNS
a.Dementia
b.Meningoencephalitis
c.Ataxia/Involuntary movement
 CVS‐ Valvular lesion
Investigations
1. Blood
Electrolytes and chemistries – Albumin, Urea, Creatinine, Na, K, Ca, Clotting profile
Hematologic tests – Hb, Iron study, Vit B12/Folate
2. Stool examination ‐ Fat malabsorption
3. Endoscopy and biopsy- Small bowel biopsies show villi containing macrophages staining positive with periodic acid‐
schiff (PAS)stain.
Treatment- Because of the tendency of whipple disease to relapse on short courses of antibiotics, most authorities
suggest a prolonged course (upto 1 y)‐ TMP/SZ or Penicillin or Chloramphenicol
Portal hypertension
Characterized by an elevated portal venous pressure (normal: 9‐10 mm Hg).
Causes/Types: grouped according to the “site” of the underlying DISEASE

1. Intra-hepatic cause:
Alternative way…..
 Cirrhosis ….most common cause
Portal Htn. causes
 Non cirrhotic portal Fibrosis
2. Pre-hepatic causes: 1. Cirrhosis
 Portal vein thrombosis 2. Non- cirrhotic etiologies
 Splenic vein thrombosis Hope you don’t expect any
further details!!
3. Post-hepatic cause:
 Hepatic vein thrombosis (Budd Chiari syndrome)
 IVC obstruction:
o Tumor invasion
o Thrombus (rare)
 Long standing systemic venous congestion
o RHF
o Constrictive pericarditis
Pathophysiological basis of Clinical features of Portal HTn: ≥ 1 of the following may appear in ANY ORDER
Pathophysiological changes Relevant clinical features
Elevated portal venous hydrostatic pressure A Ascites
Opening up of Porto‐Caval collaterals B Bleeding varices GI bleeding/ (at gastro‐esophageal
(Porto‐Systemic collaterals) junction)
C Collaterals‐ Venous prominence at superficial abdominal

wall with direction of filling “away from the umbilicus”
(Caput medusae - visible collaterals surrounding umbilicus)
PV congestion  Splenic vein congestion C Congestive splenomegaly
D Disease‐ f/o underlying disease responsible for P. Htn
Toxic products of digestion bypass the liver and E Brain: Encephalopathy‐ Portocaval/ hepatic encephalopathy
reaches systemic circulation through collateral
F Lung: Fetor hepaticus
Splanchnic (GI) congestion G Congestive gastropathy
Clinical features: Silent= Asymptomatic OR ≥ 1 of the following may appear in ANY ORDER
A Ascites: Abdominal swelling
B Bleeding varices: Hematemesis and/or Melena (Black semisolid stool)
It may progress into hemodynamic instability.
C Caput medusae (collateral at periumbilical region) and superficial abdominal venous prominence:
Direction of filling is away from umbilicus
D Features of the underlying disease
E Portosystemic encephalopathy
F Fetor hepaticus (sweetish/ ammoniacal smell in the breath of the patient due to presence of mercaptan)
G Gastropathy (causing non‐specific abdominal symptoms)
H Hypersplenism (peripheral destruction of blood cells due to hyperactive reticuloendothelial [RE] cells of spleen)
Investigation:
a. Blood: TC, DC (Pancytopenia due to hypersplenism)
1. FBC+ ESR/CRP 3. Coagulation profile: PT, aPTT, INR.
Hb: ↓ (due to GI bleed) 4. LFT: Bilirubin, Albumin, transaminase
2. Renal function: Na+/ K+ / Urea/ Creatinine
b. USG upper abdomen:
Shows portal venous diameter which can roughly a. May show splenomegaly
predict hypertension i b. Show any cirrhotic changes
Detect ascites
c. Upper GI endoscopy: To look for any varices
d. Other relevant investigations to assess the underlying cause.
Treatment:
Treatment of:
1. Ascites
2. GI bleed
3. Encephalopathy
4. Gastropathy
Complications:
1. Ascites 4. Encephalopathy
2. GI bleed 5. Gastropathy
3. Congestive splenomegaly 6. Hypersplenism
Liver/Hepatocellular disease/damage/dysfunction
Types and causes: Acute/ Chronic depends on the Cause
Acute: Rapid progression Chronic: Slow progression of liver disease

Acetaminophen (Paracetamol) overdose Alcohol
Acute viral hepatitis (HAV, HBV; HDV; HEV) Autoimmune hepatitis “CAUSES OF CIRRHOSIS”
all EXCEPT cancer & drug
Autoimmune hepatitis Budd Chiari Syndrome
Budd Chiari syndrome Biliary cirrhosis (Primary/ Secondary)
Cardiogenic shock (Shock liver) Chronic hepatitis (HCV, HBV)
Drug induced liver injury(DILI) Cancer:
Exogenous toxin (Amanita phalloides, Aflatoxin) o Primary: Hepatocellular Carcinoma
o Secondary: Hepatic metastasis
Deposition:
o Cu: Wilson
o Fe: Hemochromatosis
o Amyloidosis
Drug induced liver injury(DILI)
Fatty Liver: Non‐alcoholic fatty liver disease (NAFLD)
 Some of the “causes” can damage the Liver in “both” ways
 “Chronic” etiologies when damage the liver
 Pre/Non cirrhotic stage of liver disease
 Cirrhosis
 From a clinical point of view Causes of Chronic Liver Disease (CLD) are…..
1.Alcoholic Liver disease 2.Rest of them= Non‐Alcoholic causes
Diseased/ damaged LIVER
“Acute” etiology “Gradual” etiology

THE LIVER
THE LIVER: never becomes fibrotic Pre‐FIBROTIC stage
Acute Hepatocellular dysfunction Chronic Hepatocellular dysfunction FIBROTIC LIVER

Manifestation due to hepatocellular dysfunction
Sinusoidial resistance increases
Acute Liver disease & Pre-FIBROTIC stage of Chronic Liver disease
No Portal Hypertension Portal Hypertension
Let’s REVISE!!!!!
Acutely damaged Liver: Hepatocellular dysfunction BUT No Portal Hypertension
Chronic Liver disease:
 Pre/Non- Cirrhotic stage: Hepatocellular dysfunction BUT No Portal Hypertension
 Cirrhotic stage: Hepatocellular dysfunction AND Portal Hypertension
Let’s “REre”vise!!............................A diseased Liver IS NOT ALWAYS A CIRHHOTIC LIVER
Let’s conclude……. “Liver er case…toke to CIRRHOSIS bolei daNr korate hobey”….
My answer: Case ta daNriye jabe Kintu Daktar hoye aar daNrate parbo na
Pathophysiology effects of hepatocellular damage/ disease/failure
• Derangement of synthetic function of liver: Albumin & clotting factor synthesis
• Derangement of metabolic function: Bilirubin metabolism
• Derangement of detoxifying function: detoxifies metabolically generated waste/toxin( PV brings them to the liver)
• Derangement of hormone metabolism
• Derangement of synthesis and metabolism of endogenous vasoconstrictor and vasodilator
• Derangement of carbohydrate+ protein + fat metabolism
Clinical effects/manifestations of Liver disease: Asymptomatic!! OR ≥ 1 of the followings may appear in ANY order
Anasarca: (hypoalbuminemia)
Bilirubinemia‐ Jaundice (deranged Bilirubin metabolism)
Constituitional: Anorexia/Nausea/Weakness
Coagulopathy(deranged clotting factor synthesis)‐ Asymptomatic OR Spontaneous bleeding
Disease‐ ANY unique/specific manifestation of the UNDERLYING Etiology‐ depends on the disease
Encephalopathy (Accumulation of toxic metabolic waste products due to deranged detoxifying function)
A. Altered sensorium D. Delirium, disturbed sleep rhythm (reversal of sleep‐
B. Behavioral change (Indifference to others, childish wake cycle), disturbed mood
behavior) E. Features of cerebral edema (due to ↑ICT)
C. Confusion, coma, convulsion F. Flapping tremor
G. ↓GCS.
Fetor hepaticus
Glycemic
Hepato renal syndrome Derangement of synthesis and metabolism of endogenous vasoconstrictor and vasodilator
leads to an IMBALANCE which adversely affect Renal and Pulmonary Hemodynamics
Hepatopulmonary syndrome
Hyperestrogenemia: deranged metabolism of Testosterone leads to EXCESSIVE peripheral conversion to Estrogen
1. Testicular atrophy 3. Gynecomastia
2. Loss of secondary sexual characters (sparse pubic and axillary hair) 4. Spider nevus/ angioma
Hepatomegaly
Hypertension: Portal Hypertension ONLY when CIRRHOTIC stage develops
Asymptomatic!! OR ≥ 1 of the followings Pathophysiological changes clinical features
Ascites‐ Abdominal swelling Elevated portal venous A Ascites
hydrostatic pressure
Bleeding varices: Hematemesis and/or Melena
Opening up of portocaval B Bleeding varices GI
Collaterals‐ Visible over abdominal wall with direction of (Portosystemic) collaterals bleeding/ (at gastro-
filling “away from the umbilicus esophageal junction)
Caput medusae: collateral at periumbilical region C Collaterals- Visible over

Congestive splenomegaly abdominal wall with
direction of filling “away
Disease related features from the umbilicus”
Encephalopathy: Portosystemic encephalopathy Caput medusa- collaterals
surrounding umbilicus
Fetor hepaticus sweetish/ ammoniacal smell in the breath Portal venous congestion  C Congestive splenomegaly
due to presence of mercaptan Splenic venous congestion
Gastropathy: non‐specific abdominal symptoms D Disease- f/o underlying
disease responsible for P.
Hypersplenism: Splenomegaly with pancytopenia due to Htn
peripheral destruction of blood cells due to hyperactive Toxic products bypass the E Encephalopathy-
reticuloendothelial [RE] cells of spleen liver and reach systemic Portocaval
circulation through encephalopathy
Liver failure: conventionally this term is used when Portosystemic collateral
1.Detoxifying function fails F Lung: Fetor hepaticus
And/or Splanchnic congestion G Congestive gastropathy
2.Synthetic function fails
Liver disease patients

Clinico-investigation picture

NO evidence of Portal Hypertension +++
evidence of Portal Hypertension
Investigations
1. Blood:
CBC, CRP
Na+ K+ Urea Creatinine
LFT: (detailed Discussion on LFT in “general” volume)
 Biochemical markers of HEPATO-BILIARY DISEASE: Bilirubin, Enzymes
 Synthetic function markers: Bilirubin & liver enzymes tell us it’s a
1. Serum Albumin level DISEASED LIVER Albumin/clotting profile/
2. Coagulation profile: PT, INR (Extrinsic), aPTT (intrinsic) Ammonia tell us HOW BAD is the diseased liver
 Detoxificating function marker: Serum Ammonia level
Disease/Etiology identifying/confirming blood tests
2. Imaging:
USG abdomen:
 Abnormal appearance of Liver helps helps to diagnose liver disease & it’s stage
 Biliary disease & it’s cause
 Shows many of the effects of Liver disease: Portal hypertension, ascites, Hepatosplenomegaly
CT/ MRI of Liver
MRCP: for Pancreato‐biliary disease
3. Upper GI Endoscopy: MUST!! If Portal hypertension (hence Cirrhosis) is suspected‐ to look for Varices
4. Liver biopsy/FNAC
Treatment of Hepatocellular failure

Treatment for:
a. Ascites
b. Bleeding (or even non bleeding)varices
c. Coagulopathy
d. xx Etiology: Treat/ Remove
e. Encephalopathy End stage Liver failure: Liver transplantation
f. xx
g. Gastropathy
h. Hepato‐pulmonary/ Hepato‐renal syndrome
Portocaval collaterals
Anastomotic vessels which open up between portal and systemic circulation in a patient of portal hypertension.
Effects:
Beneficial Harmful
Reduction of portal hypertension Rupture of collateral at gastro‐esophageal region, leading to GI bleed
Toxic nitrogenous products bypass the liver & enter systemic circulation
leading to ● Portosystemic encephalopathy
● Fetor hepaticus
Sites: many but clinically relevant sites are: 1. Gastro‐esophageal region (Varices) 2. Superficial abdominal wall
Clinical features:
1. GI bleed:
 Hematemesis and/or Melena
 Hemodynamic instability
2. Visible collaterals:
Superficial abdominal venous prominence ± Caput
Direction of filling: Away from the umbilicus
3. Portosystemic shunting through collaterals:
 Portosystemic encephalopathy
 Fetor hepaticus.
Investigations: Same as portal hypertension

Treatment:
Supportive treatment
A.Airway:
To be protected: Intubation particularly if there is risk of aspiration
If required: Oropharyngeal suction
B. Breathing: Oxygen
C. Circulation:
IV fluid resuscitation (Preferred fluid of choice: Normal saline)
In case of severe bleeding: Blood transfusion
Coagulopathy (platelet, vitamin K, fresh frozen plasma).
D. Drugs: Reduces bleeding by splanchnic vasoconstriction:
 Vasopressin analogue: Terlipressin
 Somatostatin analogue: Octreotide
Definitive treatment
E. Endoscopy with Endoscopic Interventional treatment: Endoscopy confirms the presence of varices and
subsequently they can be treated endoscopically by the 2 following methods: both of which stop bleeding by variceal
“destruction”
 Endoscopic Variceal ligation (banding) {EVL}
 Endoscopic Injection sclerotherapy: Intra and para‐variceal administration of sclerosing agents:
o Ethanolamine oleate
o Sodium tetradecyl sulfate
F: Endoscopy not Feasible: this is highly unrealistic in today’s world
 Balloon tamponade of varices by Sengstaken-Blackmore tube:
F: Future bleeding prevention:
 Endoscopy‐ Surveillance Endoscopy with EVL/Sclerotherapy to achieve Eradication of varices
 Medical prophylaxis‐ Nonselective β blocker: Propranolol
(Propranolol reduces portal pressure by causing splanchnic vasoconstriction and by reducing cardiac output)
F: Failure of all the above definitive treatment: Transjugular intrahepatic portosystemic shunting (TIPS)
F: Final option: Liver transplantation (Shunt is created to DIVERT more blood from portal to systemic circulation)
So, variceal blood flow reduces BUT TIPS increases the risk of Encephalopathy
Ascites
Accumulation of free fluid in the peritoneal cavity.
Causes of ascites:
1. Ascites as part of anasarca: “systemic defect” 2. Ascites without anasarca: “local defect”
a. Cirrhosis a. Malignancy: Can be ANY malignancy with
b. CCF‐Right heart failure Peritoneal involvement BUT commonly….
c. Chronic kidney disease  GI malignancies
d. Constrictive pericarditis  Gynaecological malignancies
e. Nephrotic syndrome b. Peritoneal Infection
Theoretically this group of pts should develop “fluid  TB
accumulation” everywhere BUT practically they  Non Tubercular
develop “fluid accumulation” in ≥ 1 the potential c. Acute pancreatitis
areas, so they can come with fluid in any 1 area or
fluid in multiple areas.
Of all these diseases ASCITES is the “mode of presentation” typically in
So Ascites DOESNOT mean 1. Chronic Liver disease
But that DOESNOT mean these 3 types
it’s a case of Cirrhosis!!!! 2. Malignant Ascites of patients will ALWAYS present with
3. Peritoneal Infection: TB/ Non-TB ascites ascites!!
Causes/ mechanism of ASCITES in Cirrhosis
If you are a doctor!! If you are a “Final MB”
………………
Principal factor is Portal Hypertension which leads
to a series of local and systemic events, all of which
contribute to develop ascites
An additional factor is Hypoalbuminemia (due to
Hepatocellular dysfunction) which by reducing
COT/COP contribute to develop ascites
Principal factor “>> “powerful” additional factor
So in a Liver disease patient ……………….
Ascites typically develops in Cirrhotics
“I repeat (again)………………………………………..
that doesn’t mean ALL Cirrhotics will have Ascites”
Factors Aggravating ascites in cirhhosis:

Adherence: Nonadherence to treatment: particularly Noncompliance to diuretic and diet ( salt & fluid restriction)
Bacterial Peritonitis: Spontaneous bacterial peritonitis (SBP)
Carcinoma: Development of Hepatocellular Ca which some of the cirrhotics develop “silently”
D: Disease progression
Clinical features: In a patient of Ascites there will be OFTEN( not always!!) 2 sets of symptoms & signs
1. Those due to ascites
2. Those due to the underlying cause
Symptoms: Asymptomatic till ascites is insignificant! OR ≥ 1 of the followings
Abdominal swelling: Progression will vary according to the rate & amount of fluid accumulation
Abdominal discomfort/heaviness: severity will vary according to the rate & amount of fluid accumulation
Body weight gain
Breathlessness: ONLY in patients with MASSIVE ascites: due to “mechanical effect”
Cause related symptoms: ‘Diseases causing ascites’ will also produce ‘other symptoms’ which help us to predict the
provisional cause of ascites BUT in some patients these ‘other symptoms’ are absent‐ this may happen with any of the
disease. So, an ascitic patient will NOT ALWAYS have “cause related symptoms”
Signs
1. Due to ascites: Shifting dullness For “Final MB”s!!: 2. Flanks: full 3. Fluid thrill 4. Puddle
2. Signs of underlying diseases: If & when present help to predict the provisional cause
(same as “Cause related symptoms”)
Therefore, after assessing a patient with Ascites
Scenario 1 Scenario 2
Cause can be predicted Cause can NOT be predicted
Provisional diagnosis achieved No clear provisional diagnosis…BUT
MOST of the time a doctor will have differential diagnosis
Liver disease Malignancy Infection Occult Liver disease

Occult Malignancy
Occult infection: TB or Non-TB ascites
Investigation: Aim is to diagnose the disease responsible for ascites
1. Blood: Hb, TC, DC, CRP
2. Renal function: Na+ K+ Urea Creatinine (because CKD may be a cause)
3. Liver function test (because CLD may be a cause)
4. Urine analysis (because nephrotic may be a cause)
5. NT Pro BNP/BNP(because CCF may be a cause)
6. CXR (because malignancy may be a cause)
7. USG: may give vital clue of the underlying disease like
 Cirrhosis
 Suspected Intra‐abdominal malignancy
8. Ascitic Fluid aspiration: Often the nature of the fluid gives vital clue of the underlying disease:
Physical appearance:
 Turbid: SBP
 Hemorrhagic: Most of the time it’s Malignancy; but rarely in TB as well
Biochemistry:
 Serum Ascitic Albumin Gradient (SAAG): >1.1 gm/dL: Suggestive of portal hypertension
 High Adenosine Deaminase (ADA): Suggestive of TB
Cytology:
 WBC count:
 Neutrophilic leukocytosis: Suggestive of SBP
 Lymphocytic leukocytosis: Suggestive of TB/ Malignancy
 Atypical cells/Abnormal cell: Malignancy
Microbiology:
 Gram stain
 AFB staining + Mycobacterial culture
Special tests: GeneXpert TB: To detect M.tb DNA
“Not for Final MBs!!...only for Doctors” as this part is NOT important for exam
Further investigations: Fluid analysis may not be conclusive or even if conclusive the underlying disease often will
need further investigations to confirm the exact nature
CT Chest‐ abdomen/PET CT whole body:
 to look for a (radiologically) SUSPECTED malignancy
 to look for a (radiologically) SUSPECTED infection‐ TB
Biopsy/FNAC: from the suspected lesion
 To confirm Malignancy
 To confirm TB/ infection
Endoscopy: If ascites is suspected to be due to cirrhosis/ portal hypertension, to look for varices
Treatment of ascites
1. Diet (fluid and salt restriction)
2. Diuretic: Useful ONLY if ascites is due to “volume overload”= causes where there is a “systemic defect”
a. Spironolactone: K+ sparing diuretic; having side effects of dehydration, hyponatremia, hyperkalemia and painful
gynecomastia
b. Furosemide: loop diuretic; having side effects of dehydration, hyponatremia and hypokalemia.
3. Daily (means regularly) monitoring of the following parameters:
a. Body weight c. Fluid intake and output
b. Abdominal girth
4. Drain (Therapeutic abdominal paracentesis):
Indication:
a. Significant ascites (symptomatic)
b. Ascites refractory to diuretics
c. If required, even 5‐6 L fluid may be drained in a single sitting.
5. Treat the underlying Disease
Hepatic encephalopathy
Neuropsychiatric syndrome due to cerebral dysfunction due to hepatocellular failure and/or portal hypertension.
Pathogenesis
Underlying/Fundamental defect:
1. Hepatocellular failure: Toxic nitrogenous products and other toxins can’t get detoxified in the liver, so they reach
systemic circulation and then go to brain causing encephalopathy.
2. Portal hypertension: Due to portosystemic collaterals, toxins bypass the liver and reach systemic circulation and go to
Brain‐ after reaching the brain they cause cerebral dysfunction, leading to encephalopathy.
Toxins responsible for hepatic encephalopathy:
A. Ammonia
M. Mercaptan
M. Manganese
O. Octopamine
N. Benzodiazepine
I. Inhibitory neurotransmitters (GABA)
A. Fatty acids
Aggravating/ precipitating factors: These worsen encephalopathy in a person who have “fundamental” defect(s)
1. Conditions which cause ↑↑ NH3 production in intestine:
Increased intestinal protein load
 High dietary protein intake
 GI bleeding
Aggravating factors are CLINICALLY VERY RELEVANT: they are preventable/treatable
 Constipation
Metabolic alkalosis (which may occur in hypokalemia: Here conversion of NH3 to NH4+ is hampered
2. Hepatotoxins:
 Alcohol
 Hepatotoxic drugs
3. Infection
Clinical features
Symptoms & Signs
Altered sensorium
Behavioral change
Confusion/ Coma/Convulsion ++ ↓GCS
Delirium, disturbed sleep rhythm (reversal of sleep‐wake cycle), disturbed mood
Flapping tremor
Focal neurological signs:
a.Apraxia: Inability to perform a skillful voluntary activity which needs precision in spite of normal motor, sensory &
cerebellar function
Constructional apraxia: Tested by
 Inability to draw a 5 pointed star
 When asked to join 20 numbered points by a line, the patient either takes too much time or unable to do it
b.Jerks: Usually normal, however in deep coma: hypo/areflexia may occur
c.Plantar: Normal, however in deep coma: plantar may be bilateral extensor/ absent
Investigation: (basically investigating a “Liver patient”)
1. Blood: Hb, TC, DC, CRP/ESR
3. LFT + PT+INR+APPTT
4. NH3 level: ↑ (Ideally Arterial NH3, inreality often venous NH3 ic measured)
5. Arterial blood gas: To assess acid base equilibrium
6. USG abdomen
7. Upper GI endoscopy (to look for any varices)
8. Diagnostic ascitic fluid tap and analysis (if pt has ascites)
9. CT head: To look for any “cerebral” disease particularly the cause of encephalopathy is not clear
Treatment: ≥ 1 of the flowing depending on the clinical scenario

Airway: To be protected, if in deep coma
Aggravating factors: treat/prevention strategy
Breathing: Oxygen and if required Ventilation, if in deep coma
Aviod hepatoxins: Alcohol/hepatotoxic drugs
Bed sore prevention: Back care‐ during the period of immobility
Bleed: if any GI bleed‐ promptly treat
Circulation: IV fluid: to maintain fluid and electrolyte balance
Constipation: MUST be avoided
Capillary blood glucose monitoring: as rick of Hypoglycemia
Lactulose/Lactilol
Catheter: to monitor output
 Orally/Ryles tube
Diet: NPM and R/T feeding till very drowsy/comatose
 Enema
DVT prophylaxis: during the period of immobility
Diet: Protein restricted
Encephalopthy: recurrent/ End stage liver disease
Electrolyte imbalance: to be avoided/ treated
 Consider Liver transplant
Fever: = INFECTION‐ prompt treatment
Role of lactulose in hepatic encephalopathy Gut cleansing agent: Rifaximin
1. Being a non‐absorbable disaccharide, it gets metabolized in the gut, to form H+ which converts toxic NH3 to
nontoxic NH4+.
2. It directly acts on ammonia forming colonic flora and reduces their load.
3. It also acts as a laxative.
Spontaneous bacterial peritonitis (SBP)

Bacterial infection of ascitic fluid, in absence of any intra‐abdominal focus of infection.
Risk factors:
Any patient with ascites are at risk of SBP, however, chronic liver disease/ cirrhotic patients, particularly those with
ascitic fluid albumin level <1gm/dL are at greater risk as they and hence their ascetic fluid is often deficient in opsonins
(Opsonins: subsets of complement components and immunoglobulins who play important role in immune mechanism)
Pathogens: Organisms enter ascitic fluid either by translocation across the gut wall/ through intestinal lymphatics.
Clinical features: 1. Blood: CBC, ESR/ CRP
1. Fever 2. Blood culture sensitivity
2. Pain abdomen 3. Ascitic fluid: diagnostic criteria of SBP
3. Aggravation of ascites a. Cell count: Polymorph. >250/mm3
4. Hepatic encephalopathy may get precipitated AND/OR
5. Tenderness ± signs of peritonitis are usually absent. b. Gram stain + culture sensitivity
Investigation:
Treatment: Treatment of SBP
Established case of SBP‐ 1⁰/2⁰ prevention in high risk patients- recommended
IV Ceftriaxone ± Metronidazole by SOME authorities
• To be changed to proper oral form after few days Long term antibiotic prophylaxis
• Total duration of antibiotic therapy: 7‐10 days  Ciprofloxacin/ Norfloxacin
Hepatopulmonary syndrome (HPS)
A complication of Liver disease charaterised by pulmonary gas exchange abnormalities leading to arterial
deoxygenation, and evidence of intrapulmonary vascular dilatations
Pathogenesis: of HPS still remains unclear!!.
The hallmark of HPS is microvascular dilatation within the pulmonary arterial circulation. attributable to inadequate
synthesis or metabolism of pulmonary vasoactive substances ( most likely Nitric Oxide) by a damaged liver.
Microvascular dilatation impairs ventilation‐perfusion matching and can produce anatomical and functional shunt
physiology, leading to hypoxemia.
Clinical features:
Symptom: Breathlessness: becomes more prominent when the patient is in standing position (Platypnea)
Signs: SpO2 saturation low‐ falls further when the patient is in standing position (Orthodeoxia)
Investigation
1. Arterial blood gas (ABG)
2. Chest X Ray (CXR): To rule out ANY OTHER focal lung lesion
3. ECG and Echocardiogram: To rule out any cardiac abnormality
4. Echocardiogram with IV saline agitated microbubble (Need to know this if you consider yourself DM before becoming MBBS!!)
Under normal circumstances these microbubbles are trapped in the pulmonary vasculature and absorbed. However in
the presence of Intrapulmonary shunt( as in these patients) or Intracardiac right to left shunts, these microbubbles are
seen in the left heart very quickly.
Treatment: 1.Oxygen 2. Ventilation 3. Liver transplantation
Hepatorenal syndrome (HRS)
A state of renal dysfunction occurring as a consequence of CLD.
Diagnostic criteria:
1. Presence of azotemia: Creatinine↑
2. No other causes of kidney dysfunction
3. No improvement of renal function even after withholding diuretic therapy for 48 hours.
Pathogenesis:
 Due to CLD, there is impaired synthesis/ metabolism of vasodilators, leading to intense renal vasoconstriction;
leading to reduced renal blood flow.
 There is altered hemodynamics but no structural damage to kidneys.
Clinical features:
1. Oliguria/ anuria
2. Features of uremic encephalopathy (due to accumulation of toxins in blood)
Investigations: Renal function test: Na+ K+ Urea Creatinine: Urea, creatinine: ↑
Treatment:
1. Combination of medical agents: Midodrine/Vasopressin/ Terlipressin/Norepinephrine/Somatostatin/ Octreotide
2. Liver transplantation
Coagulopathy
Cause: Impaired synthesis of coagulation factors due to deranged hepatic function.
Clinical features: 1 of the followings
1. Asymptomatic
2. Bleeding manifestation:
External: Gum bleeding, epistaxis, ecchymosis
Internal: Intracerebral hemorrhage, GI bleed, GU bleed.
3. Circulatory crisis: If blood loss is significant, patient may become hemodynamically unstable.
Investigation: Coagulation profile
1. BT/ CT/ Platelet count
2. PT, INR (Extrinsic pathway) ↑
3. aPTT (Intrinsic pathway) ↑
- Often only PT/INR is elevated in CLD as factor VII is the first factor to get depleted.
Treatment:
1. Fresh frozen plasma transfusion, only when there is active bleeding/ before invasive procedure
2. Although it is very commonly used, vitamin K has no role, unless coexistent vitamin K deficiency is suspected
It is a common complication of portal hypertension where portal and splanchnic venous congestion leads to passive
congestion in the spleen and finally, splenomegaly.
Hypersplenism
It can occur in a patient with long standing portal hypertension and defined as the combined presence of the following:
1. Splenomegaly
2. Pancytopenia (which gets corrected after splenectomy)
3. Bone marrow hyperplasia..
Congestive Gastropathy/ Portal Hypertensive Gastropathy
Pathogenesis:
Clinical features: Asymptomatic or of the followings

4. Abdominal pain: epigastric discomfort ± pain
5. Bleeding: Overt (Melaena and /or Hematemesis) OR Occult
Diagnosis: Endoscopy shows gastric mucosal congestion and hyperemia.
Treatment: Endoscopic Interventional treatment: Argon Plasma coagulation
“Individual” Liver diseases..underdstanding them as well as the “notes”

Etiology/ cause of Liver disease
ALL SOME of them
Liver involvement/manifestation Extra‐hepatic Involvement/manifestation
Identical irrespective of the etiology Varies according to the etiology
Not mentioned in details as already mentioned before Mentioned

ONLY thing to remind……AGAIN!!
Acute liver disease causing etiology Chronic liver disease (CLD) causing etiology
Pre/Non Cirrhotic stage Cirrhotic stage
Manifestation of liver dysfunction Manifestation of liver dysfunction

++
Manifestation of Portal Hypertension
Investigations
Etiology/ cause of Liver disease
Liver related Extra‐hepatic Involvement related Etiology confirming Investigation

Treatment: Liver related Extra‐hepatic Involvement related
Everything “Liver related” has been covered already….So you will see the “heading” only!!!!
Acute viral hepatitis
Virus Incubation period Mode of transmission Acute hepatitis Fulminant hepatic failure Chronic hepatitis
HAV 15‐45 days Faeco‐oral + + -
HBV 30‐180 Sexual/Parenteral + + ++
HCV 50‐160 Sexual/Parenteral - - ++
HDV 30‐180 Sexual/Parenteral + - -
HEV 15‐60 Faeco‐oral + + (in pregnancy) -
Viral markers
HAV: Anti‐HAV antibody (Anti HAV): IgM Anti HAV (acute) and IgG Anti HAV (acute or remote)
HBV:
HBsAg:
 In most cases, the first viral marker to appear
 Appears very early during acute hepatitis and usually disappear within few months
 If persists 6 months after an episode of acute hepatitis it signifies a carrier/ chronic hepatitis stage
Anti HBs
 Appears after disappearance of HbsAg
 Presence signifies immunity EITHER achieved by vaccine OR a previous episode of acute hepatitis
 Chronic Hepatitis B patients never develop this
Anti-HBc-antibody: 2 types:
 IgM: Rises during acute infection & gets cleared off the serum after few weeks/months
 IgG: Develops during acute period and persists indefinitely
HBeAg: Secretory form of core antigen.
Appears during acute infection- marker of active viral replication. Therefore, its presence suggests high infectivity.
Anti-HBe-antibody: Appears after disappearance of HbeAg
HBV-DNA: Marker of viral replication
Quantification of HBV‐DNA denotes viral load and therefore is monitored during initiation and monitoring of antiviral
treatment response in chronic hepatitis
Chronic Hepatitis B: here it’s
Acute Hepatitis B: Confirmation of
important to know Infectivity &
virus is enough, nothing else is
viral load‐ so these are checked
relevant‐ so only this is checked
HBsAg
HBsAg HBeAg
Anti-HBe-antibody
HBV-DNA
Viral markers S: E: B: C: E: S: C
HBsAg HBeAg HBV‐DNA Anti‐HBc (IgM) Anti‐HBeS Anti‐HBs Anti‐HBc (IgG)
HCV:
Anti‐HCV: Usually appears during acute period: indicates Hep C infection
HCV‐RNA Quantification: Titre signifies viral load and is monitored during antiviral treatment
HDV: The marker is HDV‐RNA
HEV: Anti‐HEV‐antibody (Anti HEV): It is of 2 types: IgM and IgG.

Clinical features of Acute viral hepatitis: It goes through 3 stages
Pre-icteric stage Icteric stage Recovery stage:
(first few days-1week): (end of 1st week-3rd week):
Uncomplicated disease Abdo pain: RUQ pain Symptoms start to subside Symptoms and signs
Anorexia + Nausea +/‐ vomiting Bilirubinemia: Icterus appears gradually disappears
Some of them Hepatomegaly: Soft, tender Hepatomegaly: Soft, tender
Complicated disease ENCEPHALOPATHY & COAGULOPATHY

Fulminant hepatic 2 most important and common complications
failure: Encephalopathy Fetor hepaticus Fetor hepaticus
Some die
within few weeks of onset Glycemic: tendency to fall Glycemic: tendency to fall
of illness
Hepato‐renal/Pulmonary Hepato‐renal/Pulmonary
Investigation
1.Blood: Viral Markers
Hb, TC, DC, CRP/ESR: Leukopenia may be seen a. Anti‐HAV Transaminases VERY HIGH >>500
Renal function test: Na+ K+ Urea Creatinine b. HbsAg Think of 3I
Liver function test: c. Anti‐HCV Infective Hepatitis
 Bilirubin (Unconjugated and conjugated): ↑↑ d. Anti HEV Iatrogenic: Acute Drug induced Hepats
 Transaminases: ALT, AST: ↑↑↑ (often >1000 U/L)
 GGT/ ALP: ↑ (mild to moderate rise in level) Ischemic: Acute Ischemic Liver injury
 Albumin: normal/ ↓; PT, INR, aPTT: normal/ ↑
Falling albumin level and coagulation abnormalities are warning signals of a possible impending hepatic failure
2.USG abdomen
Treatment: Level of treatment MAINLY DEPENDS ON WHETHER ENCEPHALOPATHIC OR NOT
≥ 1 of the following
Absolute bed rest: till transaminase level STARTS to come down/ patient becomes asymptomatic
Admit:
 If (even if mild) manifestation of Encephalopathy
 If poor oral intake
Basic investigations: periodically Monitor INR & Albumin…(“kolkattayia style daily Bili/SGOT/SGPT is NOT required”!!)
Circulation: IV fluid if oral intake is inadequate: Dextrose
Diet: Normal palatable diet, restrict protein IF encephalopathy
Drugs:
N-Acetylcysteine: Traditionally used for Paracetamol overdose
 Avoid hepatotoxic drugs
Has been recommended for
 Antiemetic “Non- Paracetamol” Acute Fulminant Hepatic failure
Encephalopathy: Look for early signs of
Fulminant Hepatic failure‐ Encephalopathic patient: ≥ 1 of these
Aggravating factors: treat/prevention
 Airway: To be protected, if in deep coma
Aviod hepatoxins: Alcohol/hepatotoxic drug
 Breathing: Oxygen and if required Ventilation, if in deep coma
Bleed: if any GI bleed‐ promptly treat
 Bed sore prevention: Back care‐ during the period of immobility
Constipation: MUST be avoided
 Circulation: IV fluid: to maintain fluid and electrolyte balance
Lactulose/Lactilol
 Capillary blood glucose monitoring: as rick of Hypoglycemia
 Orally/Ryles tube
 Catheter: to monitor output  Enema
 Diet: NPM and R/T feeding till very drowsy/comatose Diet: Protein restricted
 Drug: N‐Acetylcysteine Electrolyte imbalance: to be avoided/ treated
 DVT prophylaxis: during the period of immobility Fever = INFECTION‐ prompt treatment
 Encephalopthy: Refractory to medical therapy‐ Liver transplant Gut cleansing agent: Rifaximin
Complications: Fulminant hepatic failure
Alcoholic liver disease
Risk factors:
1. Alcohol related: men > 40 g, particularly > 80 g/day for > 10 yrs (Women: Half of this amount)
2. Non-alcohol related: a. Malnutrition b. Gender: Females risk > males c. Coexisting liver disease of another type
Clinical features:
Pre/Non Cirrhotic stage:
 Asymptomatic OR ≥ 1 of manifestation of liver dysfunction
Cirrhotic stage:
++
 Asymptomatic OR ≥ 1 manifestation of Portal Hypertension
Clinical “Stigma”/Evidence of chronic alcohol excess:
For a doctor For a “ Final MB”
1. History of “significant alcohol consumption” Haptic facies: Wasted face with+ muddy discolouration
2. History of “significant alcohol consumption” Bilateral parotid swelling
3. History of “significant alcohol consumption” Dupuytren’s contracture: Fibrotic thickening of palmar
4. History of “significant alcohol consumption” fascia leading to fixed flexion deformity & limited
5. History of “significant alcohol consumption” extension of ring and little finger
6. History of “significant alcohol consumption” Hyperestrogenemic manifestations: More prominent than
10000!!: History of “significant alcohol consumption” in other causes of CLD
Investigation
1. Blood:
a.CBC, ESR/ CRP
 Hb: ↓ in case of GI bleed TC, DC, Platelet: Cytopenia: Due to marrow toxicity of chronic excessive alcohol
 ↑MCV: Due to coexisting folic acid deficiency( which is often present in alcoholics)
b. Renal function test: Na+ K+ Urea Creatinine: Urea‐creatinine level may be ↓ due to low catabolic state.
c.LFT:
 Bilirubin: May be ↑
 ALT, AST: Mild to moderate ↑, usually don’t exceed 300 U/L
 Typically OFTEN (due to alcohol induced inhibition of pyridoxal phosphate, a coenzyme of ALT)
 GGT, ALP: Mild to moderate ↑ (markers of cholestasis)
 Albumin: Normal/ ↑ PT, aPTT, INR: Normal/ ↑
2. USG abdomen: May show (depending on the stage)
a. Fatty liver b. Hepatomegaly c. Cirrhotic look d. Evidence of portal hypertension‐ Ascites/Splenomegaly
3. Upper GI endoscopy: To look for varices
4. Fibroscan
Treatment of alcoholic liver disease
Supportive: Complication directed treatment Definitive:
Treatment for: Etiology: Treat/ Remove
Ascites Alcohol Abstinence:
Bleeding (or even non bleeding) varices Acute withdrawal syndrome: If required, drug to control it
Coagulopathy Chlordiazepoxide/ Diazepam/Acamprosate
D xx B vitamin supplementation partcularly Thiamine
Encephalopathy as alcoholics are often deficient in B1
F xx Corticosteroid: Prednisolone for 4 weeks
Gastropathy
Hepato‐pulmonary/ Hepato‐renal syndrome End stage Liver failure: Liver transplantation
Non-alcoholic fatty liver disease (NAFLD)/ Non-alcoholic steatohepatitis (NASH)
Liver disease due to fatty infiltration (in absence of alcohol abuse) with/ without accompanying inflammation.
Risk factors:
1. BMI : High 4. Drugs (Corticosteroid/ Amiodarone)
2. Cholesterol: High 5. Endocrine (Cushing’s syndrome)
3. Diabetes
Pathogenesis: The following factor play important role in NAFLD:
Insulin resistance: It ultimately leads to lipid peroxidation and oxidative damage to the liver
(In Alcoholic liver disease, 2 important factors are: toxic effect of acetaldehyde and toxic effect of TNF)
Clinical features:
Cirrhotic stage:
++
Investigation
1. Liver disease related investigations…already covered multiple times (no more wastage of paper!!)
2. Etiology related: Risk factor stratification
 Blood:
Lipid profile
Blood glucose: Fasting and post‐prandial
Treatment
Treatment for NAFLD/NASH
Supportive: Complication directed treatment (see above!!)
Definitive: Etiology: Treat/ Remove
Risk factor modification
 Alcohol Avoid: as simultaneous alcohol may worsen NAFLD
 BMI: if high Body weight rediction
 Cholesterol: if high Hypocholestolemic drug
 DM: strict glycemic control
 Etiology: Treat any other risk factor
End stage Liver failure: Liver transplantation
Haemochromatosis
It is a disorder of iron metabolism characterized by excessive hepatic and extrahepatic iron deposition.
Pathogenesis:
HFE gene: In mutations of this gene, there is ultimately excess intestinal iron absorption.
Hepcidin: A key iron regulatory protein which is not synthetized properly. So, there is excessive hepatic iron deposition
which “spills over” into extrahepatic sites.
Clinical features: “HAEM”
H- Hepatic
Cirrhotic stage:
++
H- Heart‐ Cardiomyopathy‐ Cardiac failure/ Conduction disturbances
A-Arthralgia/ Arthritis‐ Commonly affects MCP joints (particularly 2nd and 3rd)
E- Endocrinal glands‐ Pancreas‐ Diabetes; Pituitary‐ Hypogonadism
M- Melanin (brown) + excess iron deposition in skin‐ Slate grey/ Greyish brown‐ Bronzing of skin/ Bronze diabetes
Investigation
To diagnose organ defect: To confirm hemochromatosis:
Liver: “Liver related investigations” Iron study: Serum iron: ↑↑ Serum ferritin: ↑↑
DM: Fasting and post‐prandial Liver biopsy with estimation of hepatic iron index
Heart: ECG; Echocardiogram Molecular testing: Detection of C282Y mutation
Treatment
1. Supportive treatment: For organ complications
2. Treatment of iron deposition: 1. Regular phlebotomy 2. Iron chelators: Desferrioxamine/Deferriprone
Wilson’s disease (HepatoLenticular Degeneration)

It is a disorder of copper metabolism characterized by excessive hepatic and extrahepatic copper deposition.
Risk factors: Mutations of the ATP7B gene result in impaired trafficking of copper (decrease in biliary copper excretion)
in and through the hepatocytes which leads to excessive hepatic copper deposition which then “spills over” to different
extra‐hepatic sites.
Clinical features:
H- Hepatic
Cirrhotic stage:
++
L- Lentiform nucleus Cu++ deposition‐
● Parkinsonism ● Movement disorder ● Cerebellar degeneration ● Psychiatric manifestation
D- Descemet membrane Cu++ deposition‐Brownish‐yellow ring‐ Best seen by slit lamp= Corneal Kayser-fleischer ring
Investigation
To assess organ damage: To confirm the disease:
“Liver related investigations” ↓ Serum Ceruloplasmin
MRI brain ↑ Free serum copper, but ↓ total serum copper
↑ 24 hours Urine copper excretion
Liver biopsy: if other tests are inconclusive
 High Hepatic copper concentration
Screen family members for mutation if diagnosis is
confirmed.
Treatment
Supportive: Complication directed treatment (see above!!)
 Treatment for Liver disease
 Treatment for Neuropsychiatric manifestation
Definitive:
Etiology: Treat/ Remove
 Cu++ chelating agent: D‐Penicillamine‐ If fails/ patient can't tolerate‐ Triamtene
 Reduction of Cu++ absorption from intestine: Zinc
End stage Liver failure: Liver transplantation
Primary biliary cirrhosis (PBC)
Autoantibody mediated by inflammation and subsequent fibrotic obliteration of intrahepatic biliary canaliculi.
Pathogenesis: Antibodies against Pyruvate dehydrogenase complex of canalicular cell mitochondria (Anti‐
mitochondria antiantibody) ‐ Intrahepatic cholestasis ‐ Canalicular inflammation and fibrosis ‐ Eventually liver disease
Clinical features:
P: Pigmentation
B: ↑Bile acid: Pruritus
C:
Cholestasis Fat malabsorption- Steatorrhea/ Flatulence
Vit A, D, E, K malabsorption: A- Night blindness D‐Musculoskeletal pain K‐ Coagulopathy
Conjugated hyperbilirubinemia‐ Icterus
Chronic liver disease
Cirrhotic stage:
++
Clubbing
Cholesterol: Hypercholesterolemia: Xanthelesma Xanthomata
Investigations:
1. “Liver related investigations” 2. To confirm the disease: Serum anti‐mitochondrial antibody(AMA)
Treatment:
1. Symptomatic: 2. Treatment of chronic liver disease
 Cholestasis: Ursodeoxycholic acid (UDCA)
 Pruritus: Cholestyramine (Bile acid binding agent)
 Vitamin supplementation (if required)
Autoimmune Hepatitis (AH”)
Autoantibody mediated inflammation of liver which may lead to acute hepatitis as well as chronic liver disease.
Clinical features:
Age‐ young females Association: Other Autoimmune disorders‐ Sjogren’s syndrome, autoimmune thyroiditis
Amenorrhea: Often occurs in these patients
Hepatic‐ Acute hepatitis ± fulminant hepatic failure or Chronic Hepatitis
Cirrhotic stage:
++
Investigations:
1. “Liver related investigations”
2. To confirm the disease: Serum Autoantibodies:
 Type 1 AH: Anti‐soluble liver antibody (ASLA); ANA
 Type 2 AH: Anti‐liver kidney microsomal antibody type 1 (ALKM1)
Treatment Supportive:
 Treatment for Liver disease (see above!!)
 Definitive: Corticosteroid + Azathioprine OR Mycophenolate mofetil
Liver abscess
2 TYPES: Amebic and Pyogenic
Pathogenesis:
Amebic: Trophozoite of Entamoeba histolytica- Organism enters by faeco-oral route - Cyst/ vegetative form in the intestine -
Trophozoite in the liver- Abscess formation
Pyogenic: Portal of entry:
1. Through portal vein: Pylephlebitis (infection of portal vein)
2. Through CBD: Ascending cholangitis
3. Through hepatic artery: Bacteremia
Clinical features: SAME for both
Constitutional symptoms: Focal: May not be present
Fever RUQ discomfort
++ ≥ 1 of these On examination:
Appetite loss 1. RUQ tenderness: On percussion, tenderness over
Body weakness; Bodyache right lower intercostal spaces noted
Chill (+/‐ rigor) 2. Hepatomegaly may be present.
Drowsiness
Energy lack
Investigation SAME for both

Blood: Hb, TC, DC, ESR/CRP
Blood C/S
LFT: Nonspecifically mildly deranged
USG abdomen/CT abdomen: Usually confirms abscess (Abscess is a RADIOLOGICAL diagnosis!!)
Aspiration of Pus: Microbilogical tests of the pus
Treatment
Empirically IV Ceftriaxone + Metronidazole To be changed to appropriate oral forms once patient starts to
improveTotal duration: Approx. 3 weeks.
Hepatocellular carcinoma (HCC)
Primary malignancy of liver. Remember!!...general discussion on “Malignancy”
Risk factors:
 Chronic hepatitis infection PARTICULARLY chronic HCV, also chronic HBV
 Cirrhosis (of any etiology) itself is an independent risk factor
Clinical features: Asymptomatic OR ≥ of the following
Constitutional:
Appetite loss
Body weight loss
Cachexia
D xx
Energy lack
Fever: “disease/malignancy fever”)
Loco-regional: Liver related…ABCDEFGH….
(Portal hypertension is present in some of these of patients as they may have a background of Cirrhosis)
Metastatic: Bone/Brain/Peritoneal (ascites)/Lung Involvement
Investigation
To confirm malignancy: Cytology/Histopathology: FNAC/Biopsy: Radiologically guided Liver biopsy/FNAC
To know the spread: Radioimaging (also gives the 1st clue of the diagnosis)
 Contrast CT‐ brain+ thorax + abdomen
 Contrast MRI‐ brain+ thorax + abdomen
 PET‐ CT whole body
 Isotope bone scan‐ specially for Bone mets
Overall physical assessment: CBC +LFT + KFT + Ca + ECG + Echo + PFT
Tumor Marker: Serum AFP (α‐fetoprotein): Significantly high
Treatment
Treatment of HCC

Treatment options
● Surgery and/or ● Oncomedicine and/or ● Radiotherapy
Tumor resection Liver transplantation TACE Systemic Radiofrequency ablation of tumor

TransArterial ChemoEmbolisation
TACE: Local delivery of chemotherapy with a procedure called embolization to treat cancer, most often of the liver. It is a
non‐surgical and minimally invasive procedure performed usually by an interventional radiologist.
Budd Chiari syndrome
Thrombosis of the hepatic vein
Causes:
Hypercoagulable state/ disorders:
 Anti‐phospholipid antibody syndrome
 Nephrotic syndrome
 Protein C/ protein S/ antithrombin 3 deficiency
Idiopathic
Clinical features:
1. Sudden RUQ pain 3. Patient may develop fulminant hepatic failure
2. Tender soft hepatomegaly 4. Ascites.
Investigation
1. USG abdomen with Doppler study
2. CECT abdomen
3. Coagulation studies
Treatment: Anticoagulation
Wernicke Korsakoff Syndrome
It is a neurodegenerative complication of vitamin B1 deficiency, most commonly seen in chronic alcohol abusers.
Pathogenesis:
Degeneration of different areas of brain: mammillary body/ thalamus/ median temporal lobe/ cerebellum. Chronic
alcohol abuse interferes with absorption and metabolism of thiamine, often leading to severe thiamine deficiency.
Clinical features: WKS has two components: 1. Wernicke’s encephalopathy 2.Korsakoff psychosis
Wernicke’s encephalopathy: Usually these symptoms are reversible with thiamine replacement therapy
1. Ataxia
2. Ophthalmoplegia
3. Confusion
Korsakoff’s psychosis: Irreversible
1. Cognitive symptoms: Insomnia, Anxiety, Difficulties in concentration, Loss of memory for the immediate past, and
gradual degeneration of mental state
2. Confabulation: Incorrect memories that the patient holds to be true, and may act on, arising spontaneously without
any provocation. (In viva table we all “confabulate”only difference is there is a provocation!!)
3. Patient may have features of Wernicke’s encephalopathy
Investigation 1. MRI of brain: may show some “suggestive” changes 2. Vitamin B1 estimation
Treatment
1. Prevention: For ALL chronic alcoholic‐ must receive high dose thiamine
In patients with H/O significant alcohol abuse till recently, IF such a patient requires IV dextrose containing fluid, must receive
high dose thiamine before/ at least along with the fluid. (glucose oxidation is a thiamine consuming process and therefore,
may unmask any underlying deficiency and may precipitate Wernicke Korsakoff syndrome)
2. Established cases: High dose thiamine replacement.
Child-Pugh Score for chronic liver disease/ cirrhosis…….(”For Short Note obsessed”)
Points/Score 1 2 3
Ascites None Mild‐ moderate Severe
(diuretic responsive) (diuretic refractory)
Encephalopathy None Mild‐ moderate Severe
Albumin (gm/dL) >3.5 2.8‐3.5 <2.8
Bilirubin (mg/dL) <2 2‐3 >3
INR <1.7 1.7‐2.3 >2.3
Interpretation
Total score 5‐6 7‐9 10‐15
Prognosis Least severe Liver disease Moderately severe LD Most severe LD
Cirrhosis……
Nothing new!!!...Basically “summary” of last few pages as we have already read EVERYTHING aboutit
It is a condition characterized by:
 Clinically by: Hepatocellular dysfunction + Portal hypertension
 Histopathologically by: Hepatic fibrosis + Necrosis + Regenerative nodules (pseudo‐lobules) + Architectural
destruction of liver.
Causes: ABCDE of chronic liver disease
Clinical features: ABCDEFGH including Portal Hypertension of liver disease

Disease related features
Alcoholic Cirrhosis: History….history….& history!!
Chronic Hepatits B/C: History..patient says “ I have hep B/C”!!! (A doctor who claims to diagnose B/C clinically is “a bc”)
Primary biliary cirrhosis (PBC):
 Clubbing Underlying diseases/causes
 Pigmentation Don’t expect to diagnose these clinically even the biggest “Cirrhosisologist” doesn’t
Wilson’s disease: MOST of these diseases are diagnosed from investigation results
 Kayser–Fleischer ring therefore from a clinical point of view Causes of chronic liver disease are…..
 Involuntary movements
1.Aloholic Liver disease 2.Rest of them= Non‐Alocholic causes
 Psychiatric manifestation
Hemochromatosis:
 Cardiomyopathy: Heart failure
 “Bronzing” of the skin
NAFLD: presence of risk factors
Investigations
Liver related Etiology related
CBC, CRP
Chronic Hep B: HBsAg/ HBeAg/ Anti-HBe-antibody/ HBV-DNA
Na+ K+ Urea Creatinine Chronic Hep C: Anti HCV/ HCV RNA
LFT: Hemochromatosis:
Bilirubin  Iron study: Serum iron: ↑↑ Serum ferritin: ↑↑
AST, ALT  Liver biopsy with estimation of hepatic iron index
GGT, ALP  Molecular testing: Detection of C282Y mutation
Albumin, PT, aPTT, INR Wilson disease:
NH3 level ↓ Serum Ceruloplasmin
↑ Free serum copper, but ↓ total serum copper
USG abdomen
↑ 24 hours Urine copper excretion
Upper GI endoscopy: any varices Liver biopsy: High Hepatic copper concentration
Diagnostic ascitic fluid aspiration: Autoimmune Hepatitis: Anti SLA/Anti LKM
 SAAG >1.1. gm/dL
 PMN >250: suggestive of SBP
Treatment of chronic liver disease
1. Treatment of complications:
Disease/Etiology related treatment
Ascites:
Alocholic Cirrhosis: STOP it!!
 Dietary Na+ and water restriction
(Not that Others will continue heavy drinking!!)
 Diuretics (Loop diuretics/ K+ sparing diuretics)
Chronic Hep B/C: Antiviral
 Daily body weight monitoring Biliary Cirrhosis: Symptomatic
 Daily intake‐output chart Drug induced: Stop the offending drug
 Drainage: therapeutic ascitic fluid aspiration Hemochromatosis: Iron chelator
Bleeding varices: Wilson disease: Cu chelator
 Circulation: IV fluid + blood transfusion) NAFLD: Risk factor modification
 Drugs (Terlipressin) AH: Steroid/Azthioprine/Mycophenolate
 Endoscopy
 Endoscopic band ligation
 Sclerotherapy
 Prevention: β‐blocker
Coagulopathy:
 Fresh frozen plasma in case of active bleeding
Encephalopathy:
A. Avoid alcohol/ hepatotoxic drugs End Stage Liver disease
B. Urgently treat any associated GI bleed Transplantation
C. Prevent/ treat constipation ESLD= Medically unmanageable/refractory
D. Dietary protein restriction  Ascites
E. Treat any electrolyte imbalance  Bleeding varices
F. Treat any associated infection  Encephalopathy
G. Gut cleansing agent (Rifaximin)  Hepatorenal
 Hepatopulmonary
Gastropathy: Endoscopic Argon Plasma coagulation
Hepatopulmonary: Ventilation
Hepatorenal: Dialysis
I expect you have realized why did I say “a summary” of previous pages!!!
PS:
CLD in Non-cirrhotic stage overall “synopsis” remains the same….EXCEPT (as discussed NUMEROUS TIMES)
Portal Hypertension part is not applicable
ENDOCRINE
Endocrine
Thyroid
Hypothalmic hormone: TRH (Thyrotrpoin Releasing hormone)
stimulates Pituitary release of TSH
Pituitary hormone: TSH (Thyroid stimulating Hormone/Thyrotropin)
Feedback ● Stimulus for thyroid hormone production by the thyroid gland
(+)/ (-) ● Also exerts growth effects on thyroid follicular cells
Gland hormones: T4 (Thyroxine/Tetraiodothyronine) & T3 (Triiodothyronine)
T3, is the active form of thyroid hormone. Though it represents only 20% of the released hormone, the majority of T3
comes from the peripheral conversion of T4 to T3
T4 and T3 can then exert negative feedback on the anterior pituitary with high levels of T3/T4 suppressing TSH
secretion and low levels of T3/T4 stimulating TSH release (This feedback effect is a PHYSIOLOGICAL phenomenon
and gets “AGGRAVATED” in pathological state of the gland)
Thyroid hormone: “clinically relevant” Physiological functions ONLY mentioned here

Atmosphere of the body: induces Thermogenesis
Basal metabolic rate: Increases
 Sytemic
 Of almost EACH organ: so “activity” of many organs are influenced by thyroid hormones
CNS:
 During the prenatal period, it is needed for the maturation of the brain.
 Throughout the life: affect mood +concentration+ memory + alertness
“Dietary” effects:
 Induce lipolysis or lipid synthesis depending on the metabolic status
 Stimulate the metabolism of carbohydrates
 Anabolism of proteins. Thyroid hormones can also induce catabolism of proteins in high doses
Dermal: Influences breakdown of protein-mucopolysaccharides (Glycosaminoglycans and others) of dermal
connective tissue network. These protein-mucopolysaccharides are HYDROPHILIC (binds water)
Electrolyte: Sodium “conserving” hormone
Fertility:Thyroid hormone affects Fertility
Gynaecological: Affects menstruation, ovulation
Hypothyroidism
Types:
Primary: diseases intrinsic to the thyroid gland
Secondary: diseases Extrinsic to the gland: Underactive Pituitary leads to underproduction of TSH, so Thyroid
becomes underactive
Causes of Hypothyroidism:
Goitrous causes (i.e tendency to enlarge in size) Non-goitorus causes

I: Iodine deficiency P: Post I131 ablation
I: Inflammatory: Hashimoto’s Thyroiditis P: Post Thyroidectomy
I: Iatrogenic: Amiodarone/Lithium P: Postpartum Thyroiditis
I: Inborn error: Dyshormonogenesis P: Pituitary disease(Secondary hypothyroidism)
(due to enzyme deficiency)
All “I”s & all “P”s except Pituitary diseases: Primary Hypothyroidim ( so here TSH LEVEL will be HIGH)
“I”s: Glandular tissue is intact, so HIGH level of TSH can exert it’s “growth effect” on the gland leading to Goitre
“P”s: Glandular tissue is destroyed/ shrinks: so HIGH level of TSH CANNOT exert it’s “growth effect”, so NO goitre
Pituitary disease: Secondary hypothyroidism (so here TSH LEVEL will be LOW)
Clinical features: Develops very insidiously and can be widely variable
A: Asymptomatic
OR
A: Asthenia: Weakness/lack of energy/lethargy
A: Appearance: facial puffiness with coarse features
dry lustureless hair with tendency of Hair fall
B: Body weight: gain
BP: DBP rises
C: Cold intolerance
C: Constipation
C: Congenital cases
 Children: growth failure, delayed dentition, pubertal delay or even rarely, precocious puberty.
 Neonates/infant: hoarse cry, prolonged jaundice, mottled skin, umbilical hernia, constipation, poor feeding
CNS:
 A:attention deficit
Biochemical “manifestation”
 B: behavioural disturbance
D: Dyslipidemia
 C: Concentration Lack
E: Electrolyte disturbance: Hyponatremia
 D: Dementia
 E: Extereme deficiency: Myxoedema coma/crisis: confusion/convulsion/coma
Dermal: dry, thick, coarse skin
E: Extremity:
 Bradycardia
 Carpal tunnel syndrome( Entrapment neuropathy of Median nerve)
 Skin: dry, thick, coarse with mildly edematous (deposition of hydrophilic protein-mucopolysaccharides)
 Delayed relaxation time of jerks: best elicited in ankle jerk
F: Fertility issues: subfertility/infertility
G: Goitre: MAY be visibile
G: Gyane: Erratic/irregular cycle
H: Husky voice
Investigations:
Blood: Subclinical hypothyroidism
1.Thyroid function test (TFT): TSH, FT4, FT3 TSH is high, but the T4 is normal
1. Primary Hypothyroidism: low T4 and a high TSH level
2. Secondary Hypothyroidism: low T4 & low TSH
Parameter Subclinical Hypothyroidism Overt Primary Hypothyroidism Secondary Hypothyroidism
T4 Normal Low Low
TSH High High Low/Normal
2. Anti-TPO antibodies: Autoimmune thyroiditis: high levels of Anti-TPO antibodies
“Footnote” about TFT( Not a “must know” information)

T3 is not routinely measured in the diagnosis of hypothyroidism as in milder forms of hypothyroidism, the increased TSH stimulates the
selective production of T3 and this may result in a high/normal T3. However, in severe varieties of hypothyroidism, the T3 is also low.
Free hormone(FT4/FT3) estimations (which estimate the concentration of thyroid hormones that are not bound to circulating proteins)
are advantageous as they measure the metabolically active component, and also because they are not affected by conditions which
increase or decrease the levels of thyroid-hormone binding proteins.
Treatment: Hormone replacement therapy: Oral L-thyroxine
Decision to treat/ not to treat: OFTEN depends on the TSH level
Primary hypothyroidism Secondary hypothyroidism: Always start treatment
1. Overt Hypothyroidism: Always start treatment (there is still No “TSH tablet”!!..so treated with L-thyroxine)
2. Subclinical hypothyroidism
 TSH > 10 mIU/L: Always start treatment
 TSH levels of 5-10 mIU/L: Treat ONLY under certain clinico-biochemical situations
Pregnancy/planning for pregnancy Very high titre of Anti-thyroid antibodies

Infertility Dyslipidemia
Menstrual irregularities Unexplained hyponatremia
Goiter
(Normal Upper limit: although varies slightly with the ASSAY method 5 mIU/L is considered to be the “cut off”)
Principles of Thyroxine therapy
1. Dose: depends on the body weight. Dosing regime- ‘’Start low and go slow” particularly in elderly patients
2. Long term therapy, most of the time to be continued lifelong
3. Ideally to be taken in the morning in empty stomach
Patient monitoring/surveillance: This is for ALL patients who are on L-thyroxine replacement therapy
Target: to achieve & maintain Euthyroid state (means biochemically TFT should be brought back to NORMAL)
Periodic(4-6 monthly) TSH estimation- for surveillance FT4 and FT3 estimation is not essential
TSH high TSH Low
High/Low TSH…. means circulating thyroid
Undercorrection Overcorrection hormone is still giving Pituitary a “STRONG”
feedback in an attempt to achieve homeostasis
Compliance issue ??
…..Now think about the physiology of
Dose to be decreased
Pituitary- gland axis!!
Non Compliance Compliance okay
Rectify compliance Dose to be increased
SubClinical Thyroid Disease….just for your information (nothing more!!)

Though it is recognized that patients with SCTD may have subtle symptoms of thyroid dysfunction, the definition is
purely a biochemical definition: SCTD is defined as serum free T4 (FT4) and total or free T3 (FT3) levels within their
respective reference ranges in the presence of abnormal serum TSH levels. Serum TSH is undetectable or low in
subclinical hyperthyroidism (SHyper), and it is increased in subclinical hypothyroidism (SHypo)
Myxedema coma (myxedema crisis)
Myxedema coma (myxedema crisis) is a rare but life-threatening condition that represents severe hypothyroidism
with physiological decompensation.
At risk patients: Occurs in patients with long-standing Undiagnosed or Undertreated hypothyroidism
Precipitating factor(s): “Physiological” stress:
1. Critical illness: eg. Infection, CVA, Heart failure 2. Severe Trauma 3. Post-operative stress
C/F
Hypothyroidism: PMH of hypothyroidism: may be +, but background hypothyroidism may be undiagnosed, so
Myxedema crisis can be the initial/first presentation of the patient
Hypothermia
Heart rate: Bradycardia
Hypotension (poor cardiac contractility due to profound deficiency of thyroxine)
Hypoactivity: Altered sensorium/Behavioural disturbance/Confusion/Convulsion/Coma/Delirium/Drowsiness
Hypoventilation: Drowsiness (CO2 retention due to central depression of ventilatory drive)
Hyponatremia: asymptomatic or symptomatic (Lack of thyroxine promotes Natreuresis)
Hypoglycemia: asymptomatic or symptomatic
Investigations:
Diagnostic purpose: Thyroid function test: Hypothyroid pattern:
Elevated TSH with low FT4 and FT3 indicates primary thyroid disorder
Low TSH level with low FT4 and FT3 indicates pituitary or hypothalamic dysfunction.
Assessment purpose: To look for any ppting factor+ biochemical disturbance associated with severe hypothyroidism
CBC Electrolytes: Na/K
CRP ABG
Ur+ Cr ECG
Infection/sepsis screen: CxR/Urine R.E/M.E/C.S+ Blood C/S+ Procalcitonin
Treatment:
Definitive:
1. Thyroxine replacement: High dose Levothyroxine (Ideally initially IV: IV thyroxine preparation is NOT available
in India, so we rely on PO/Ryles tube administration)
2. Corticosteroid: IV Hydrocortisone: until (an undiagnosed) adrenal insufficiency is excluded.
[Because if there is an underlying adrenal insufficiency there is a potential risk of precipitating acute adrenal insufficiency caused by
the accelerated metabolism (that follows T4 therapy) which increases demand of cortisol. Primary hypothyroidism may have
concomitant primary adrenal insufficiency as “autoimmune hypos” may affect multiple glands simultaneously. Secondary
hypothyroidism which is due to hypopituitarism, so also may have secondary adrenal insufficiency]
Supportive: ≥ 1 of the followings depending on clinical scenario

1. Hypothermia:
 Passive rewarming using ordinary blankets and a warm room
 Active rewarming using external devices: Bair Hugger blanket is the temperature management system
2. Hypotension: IV fluid resuscitation. Refractory hypotension may need vasopressors
3. Hypoventilation: Intubate and ventilate
4. Hyponatremia: IV Saline
5. Hypoglycemia: IV Dextrose
6. Treat any precipitating factor: Antibiotic: as sepsis is a common ppting factor
Hashimoto thyroiditis
Characterised by destruction of thyroid cells by various cellular and antibody-mediated immune processes.
Pathophysiology
Initiating process - Ab to thyroid antigens- Anti-thyroid peroxidase (anti-TPO) + Antithyroglobulin (anti-Tg)
Inadequate hormone production and secretion Glandular size enlargement, but ultimately shrinks
Gradual destruction of the gland

Permanent Hypothyroidism
C/F
1. Many are asymptomatic till T4/T3 becomes significantly low
2. Frank features of Hypothyroidism……(if Hashimoto comes as Long Q…write c/f in details)
3. Goitre- initially and may be significant in size but ultimately gland shrinks
5. Associated autoimmunity diseases - Pernicious anemia, Adrenal insufficiency and Ty1 DM etc
Investigations
1. TFT- TSH + FT4, FT3 - normal/low (Low TSH with Normal T4 & T3 = Subclinical Hypothyroidism…see previous topic)
2. Antibody-Anti TPO/Anti TTG- confirms Hashimoto, however rarely antibody negative
2. USG of thyroid
Management
Pharmacotherapy: Thyroid hormone replacement- dose titrated Levothyroxine sodium administered usually for life.
Surgery: Indications for surgery include the following:
Large goitre with obstructive symptoms: dysphagia/ stridor (caused by external obstruction)
de Quervain thyroiditis/Subacute thyroiditis

A self-limited virus induced thyroid disease associated with a triphasic clinical course of thyrotoxicosis,
hypothyroidism, and finally complete recovery of thyroid function.
Pathophysiology
Initiating process –Viral Infection
Follicular destruction No Glandular enlargement, but tenderness+
Preformed T4 &T3 may "leak" into the circulation Transient Thyrotoxicosis (often symptomatic)
Gradual Exhaustion of follicles Hypothyroidism
Complete Recovery as viral infection settles

C/F
1. Systemic features- Fever/Sore throat 2. Frank features of Hypothyroidism
2. Transient Thyrotoxic features 4. Goitre- initially with significant tenderness
Investigations
1. ESR- often high 3. Antibodies- Negative
2. TFT- depends on the stage of the disease 4. USG of thyroid
 Thyrotoxic phase- TSH + FT4, FT3 – high
 Hypothyroid phase- TSH↑ + FT4, FT3 - normal/low
 Recovery phase and thereafter- Normal
Treatment
1. NSAID- for fever/sore throat 2. Thyrotoxic phase- symptomatic control with Beta blocker
3. Thyroid hormone replacement- usually not required as complete recover is the outcome in almost all cases
Riedel thyroiditis
A chronic inflammatory disease of the thyroid gland, probably autoimmune in nature, characterised by dense fibrosis
that replaces normal thyroid parenchyma and often invades adjacent structures of the neck
C/F- any ≥ 1following
1. Thyroid manifestations- Many are euthyroid, but permanent hypothyroidism can develop
2. Compressive manifestations-
 Stridor - tracheal compression  Hypoparathyroidism
 Hoarseness - RL nerve involvement  Dysphagia- Oesophageal compression
3. Goitre- hard, fixed, painless goitre- the feel closely resembling anaplastic carcinoma. The character of the thyroid
gland is often described as stony or woody
4. Few ultimately develop extracervical manifestation of multifocal fibrosis-retroperitoneal/mediastinal fibrosis
Investigations
1. TFT- high TSH+ normal/low T4/T3
2. FNAB (B=biopsy)-fibrotic changes in the gland; however, cannot always reliably distinguish between RT and
anaplastic thyroid carcinoma and open surgical biopsy is required.
Treatment
1. Pharmacotherapy- Corticosteroids and Tamoxifen (both help- how??....wait till you become a DM endocrine!)
2. Thyroid hormone replacement
3. Surgery- serves dual purpose of establishing the diagnosis and relieving tracheal compression
Thyrotoxicosis
Thyrotoxicosis: the clinico-biochemical state resulting from excess thyroid hormone in the circulation/ system
(irrespective of the source where it is coming from)
Hyperthyroidism: an overactive Thyroid gland i.e sustained overproduction of hormone from the thyroid gland
Thyrotoxicosis with hyperthyroidism Thyrotoxicosis without hyperthyroidism

Primary hyperthyroidism Exogenous:
Immune: Graves’ disease ● Iatrogenic: Overcorrection of Hypothyroidism
Intrathyroid Hormonally active autonomous nodule(s) Ectopic Thyroid: Ovarian Teratoma(stuma ovarii)
 Solitary toxic nodule Excess release of stored hormone: Thyroiditis
 Multinodular disease ● Dequervians
Iodine excess (Jod-Basedow phenomenon) ● Post partum
Secondary hyperthyroidism
Pituitary disease: TSH-secreting pituitary adenoma
Pregnancy related: Gestational Trophoblastic disease (very high level of Beta HCG “MIMMICKS” TSH due to it’s
structural similarity with TSH)
Clinical manifestations of a thyrotoxic patient
Manifestations due to EXCESS circulating thyroid hormone Manifestations UNIQUE to the underlying disease
Hormone dependent & cause independent Disease dependent & hormone independent
CAUSED by hormone excess CAUSED by pathophysiology of that particular disease
Therefore these manifestations are present in May occur with each “thyrotoxicosis producing disease”
EACH thyrotoxic patient irrespective of the However that of Grave’s disease is most unique (& important)
cause or disease responsible for thyrotoxicosis
Most of the thyrotoxic manifestations are due to excess hormone leading to
 Increased sensitivity to the sympathetic nervous system
 Increased Basal metabolism
Graves’ disease
Autoimmune disease characterized by a triad of Endocrinopathry, Opthalmopathy & dermopathy.
1.Endocrinopathy: Antibodies bind to the receptors “meant for TSH” of the thyroid cells & stimulates
thyroid hormone production & growth of the gland in an UNCONTROLLED manner
 Functional alteration: Hyperthyroidism with Thyrotoxicosis
 Sructural alteration: increase thyroid vascularity and growth Goiter
Activating 2. Infiltrative/Graves Ophthalmopathy
Antibody antibodies bind to the retro-orbital tissues T-cell inflammatory response + release of cytokines &
activation of fibroblasts accumulation of glycosaminoglycans + fibrofatty tissue/material
Retro-orbital accumulation of these may lead to
 Compression and/or Inflammation of Optic nerve
 Compression and/or Inflammation of EOM/EOM tendon
 Forward protrusion of the globe(eye ball)
3.Infiltrative dermopathy Activation of dermal fibroblasts leading to typical skin change: most
commonly seen in the anterior leg: hence called Pretibial myxedema
Endocrinopathy, Dermopathy & Opthalmopathy are independent of each other and therefore can occur in an
isolated manner or any varying combination
** “stimulating” antibodies are functionally SIMILAR to TSH but DON’T “listen” to the normal feedback inhibition
Thyroid Eye disease
Thyrotoxic eye manifestations Graves’ Opthalmopathy

Manifestations due to excess circulating thyroid hormone Manifestations due to Infiltrative Ophthalmoapthy
Sympathetic overactivity causes Spastic Muller’s muscle 1. Forward protrusion: Proptosis/Exophthalmos
Lead retraction Exposure keratitis: Red/gritty/painful eye
Stare look with infrequent blinking Extreme/Severe cases: Vison loss
Lid lag: lid doesn’t follow the globe during downward gaze Lid edema/redness
(Sensitisation of Mullers’s muscle to circulating Catecholamine) 2. Extraocular muscles(EOM) weakness:
Dipolpia
Weakness of EOMs ellictable
3. Optic nerve damage: Vision loss
For “Non MBBS- MS Opthlmos/ DM endocrinos” For “Final MBs”!!

NOSPECS classification of Grave’s Ophthalmopathy Dalrymple’s sign: Lid retraction
Score Kocher’s sign: Stare look
0 No signs or symptoms Stellwag sign: incomplete and infrequent blinking
1 Only signs Von graffe’s sign: Lid lag
2 Soft tissue involvement, with symptoms and signs Mobius sign: poor convergence (MR palsy)
3 Proptosis Goffory sign: absent creases in the forehead on
4 Extraocular muscle involvement superior gaze
5 Corneal involvement PS: Though it’s a favourite topic of MANY “……”
6 Sight loss (hmm..hmm!!) particularly in surgery ward…Thanks to
Corona, you don’t have to face them
Proptosis vs Exopthalmus…another “favourite” of the same “….”
Basically NO DIFFERENCE!!!!... NO DIFFERENCE!!!!.... NO DIFFERENCE!!!!
Proptosis: defined as abnormal protrusion of the eyeball (“globe”) beyond the orbital margin
Although the word “Exophthalmos” is synonymous to it, it has become customary( NOT compulsory!!) to use the
term exophthalmos to describe a proptosis secondary to Thyroid eye disease( probably because “E”ndocrinologists
love the letter “E”!!)
Clinical diagnosis: by “looking” at the patient’s eyes

Confirmation: Hertel’s exophthalmometer: the distance between lateral orbital rim & corneal apex is used as a
measure for proptosis. Normally the distance varies between 10- 21 mm and is symmetrical in both eyes. Therefore a
distance of >21 mm or more than 2 mm asymmetry between the two eyes is abnormal.
Causes: depending on the cause it can be Unilateral or Bilateral
Vascular: Rero orbital “SOLs”: Aneurysm/Tumor/ Carotido-Cavernous fistula
Endocrinopahty: Graves’ disease(usually Bilateral)
Inflammatory So, Proptosis/Exophthalmus DOES NOT automatically mean
 Orbital cellulitis/Abscess/TB/Fungal granuloma it’s Graves/Thyroid patient!!
 Sarcoidosis/Histiocytosis/
For Next section…..Let’s recapitulate!!!!
Clinical features of a Thyrotoxic patient:

Includes
“EXCESS hormone dependent” manifestations ++ “DISEASE dependent/related UNIQUE” manifestations
NO relation with excess hormone
DOES NOT vary with the disease Causing Thyrotoxicosis VARIES with the disease Causing Thyrotoxicosis
Severity may vary depending on the degree of “excess hormone” Each disease may cause it’s unique manifestations
Present in ALL thyrotoxic patients but MOST COMMON in Graves disease
IRRESPECTIVE of the disease Causing Thyrotoxicosis
Clinical features of a Thyrotoxic patient:
The clinical manifestations of thyrotoxicosis are independent of its cause. However, certain features of a
THRYOTOXIC patient like size of the gland, presence or absence of extra thyroidal manifestations vary with the
underlying etiology and may provide clues to this.
Asymptomatic
OR ≥ 1 of the followings Thyrotoxic eye manifestations
 Lead retraction
Appearance:
 Stare look with infrequent blinking
 Face: Anxious/ restless
 Lid lag: lid doesn’t follow the globe during downward gaze
 Eye: Eye manifestations Manifestations due to Infiltrative Ophthalmoapthy: only in Graves’
BP: may be high  Forward protrusion: Exposure keratitis:
Body weight: rapid loss (but appetite preserved)  Red/gritty/painful eye
CNS: Neuropsychiatric  Vison loss
 Attention deficit; Anxiety  EOM weakness: 1. Diplopia 2. Weakness of EOMs ellictable
 Behavioural disturbance: Irritability  Optic nerve damage: Vision loss
 Concentration lack
 Disturbed mood
 Extreme cases: agitation/behavioural disturbance/confusion/convulsion/ delirium/emotional lability
Dermal: moist skin
Diarhhoea (Hyperdefecation)
Extremity
 Tachycardia
 Tremor: fine tremor
 moist palm
 Hyperreflexia
 Graves Dermopathy: ONLY in Graves’ disease: Bilateral, firm, shiny pink to purple-brown plaques or
nodules particularly over the shin: also called Pretibial Myxedema. Hair follicles are sometimes prominent,
giving a peau d'orange texture. Localised edema may develop.
Fertility: subfertility
Feels hot (Heat intolerance)
Gynae: Erratic mensturation
Goitre: ONLY in certain diseases
 Graves’ disease: May be diffuse goiter with Thyroid bruit
 Toxic adenoma: Nodule(s) may be palpable
Investigations:
Aim: 1.To diagnose thyrotoxic state 2.To diagnose the underlying disease
Biochemical confirmation of thyrotoxicosis: Thyroid function test: FT4, FT3, TSH estimation:
Typically shows Elevated FT4 and FT3; TSH level: varies according to the underlying disease
Supressed: Elevated:
Primary Hyperthyroidism Secondary (Pituitary disease) Hyperthyroidism
Thyrotoxicosis without hyeperthyrodism
Therefore TSH level acts an index of the pattern of underlying disease
Subclinical hyperthyroidism: suppressed TSH with Normal FT4 &FT3
 The ratio of T4 to T3 frequently has a characteristic pattern in different thyrotoxic states.
 Graves’ disease and toxic nodular goiter typically: increasedT3 production, with a T3 /T4 ratio > 20.
 Thyroiditis, I2 exposure, or exogenous levothyroxine intake: T4 is the predominant hormone and T3 /T4< 20.
 T3 toxicosis: A small number of patients may present with an increased FT3 and normal T4: called“T3 toxicosis”.
To diagnose the underlying disease: Nature of these tests depend on the pattern of Thyroid function test
Primary Hyperthyroidism pattern: “Investigate thyroid”
TSH-R antibodies: Grave’s disease
Imaging
1. Thyroid ultrasound: USG appearance is often suggestive of a particular underlying disease:
 Diffuse enlargement with increased blood flow: Graves’ disease
 Identification of thyroid nodule(s): Toxic Nodular disease
2. Nuclear medicine scanning: Radioactive iodine uptake scan: shows an increased uptake by an overactive gland
Distribution/ Pattern of increased uptake varies according to the disease:
 Diffusely increased uptake: Graves’ disease
 Foci/focus of increased uptake: Solitary toxic nodule/ Multiple toxic nodule (“hot nodule”)
Secondary Hyperthyroid pattern: (“Investigate Pituitary”): Pituitary function test +Imaging of Pituitary
Treatment of thyrotoxicosis
Supportive: Definitive: Curative treatment of the underlying disease
Manifestation directed Hormone directed Disease directed & depends on the underlying disease
Beta blockers Antithyroid drugs Surgery Radio I2 ablation
Manifestation directed: Sympatholytic drugs

1. Nonselective Betablocker: Propranolol 2.Cardioselective Betablocker if Arrhythmia is the only problem
Propranolol blocks the response to catecholamines at the receptor site and ameliorate some of the manifestations of
thyrotoxicosis like tremor, palpitations, anxiety, excessive sweating, eyelid retraction, and tachycardia: effects
appear to be mediated largely through modulating the increased sensitivity to the sympathetic nervous system
induced by excess thyroid hormone. Propranolol (but not other β-adrenergic agents) may also weakly block the
conversion of T4 to T3 via a mechanism independent of its effect on catecholamine signaling.
Antithyroid drugs: used to make the patient Euthyroid by the the time a definitive treatment is being contemplated
therefore long term term use is reserved only when a definitive treatment is not feasible
1. Imazoles: Carbimazole/Methimazole 2.Propylthiouracil
Radioablation: Radioactive Iodine ablation: 131I has become the most widely used therapy for hyperthyroidism.
RAI is considered effective, safe, and relatively inexpensive. The ionizing effect of β particles destroys the thyroid cells
by an early inflammatory response, necrosis of follicular cells, and vascular occlusion. Subsequently chronic
inflammation and fibrosis result in a decrease in thyroid size and an impaired ability to secrete thyroid hormone.
Ultimately, almost all patients develop hypothyroidism following 131I.
Surgery: Subtotal or total thyroidectomy
Indication of surgery:
Large goiter causing compressive symptoms or cosmetic disfigurement
Suspicion of malignancy
Graves’ ophthalmopathy (may paradoxically worsen after RAI ablation)
Pregnancy contraindication of RAI
Children contraindication of RAI
Patient preference
Treatment of Graves’ disease
Rx of Endocrinopathy Rx of Ophthalmopathy Rx of Dermopathy

Treatment of thyrotoxicosis
Supportive: Definitive: Curative treatment
Manifestation directed: Beta blockers Surgery
Hormone directed: Antithyroid drugs Radio I2 ablation
Rx of Ophthalmopathy Ophthalmology referral
Eye protection: Drugs: Methyprednisolone/Cyclosporine/Rituximab
Protective gears: Eye pad/Glass Orbital decompressive surgery
Lubricant: Artificial tear drop Orbital radiotherapy
Rx of Dermopathy: Topical corticosteroid
Thyrotoxic crisis
Thyroid storm (thyrotoxic crisis) is an acute, life-threatening, hypermetabolic state induced by excessive release of
Thyroxine in individuals with thyrotoxicosis.
Pathogenesis: Severely exaggerated effects of Thyroxine due to increased release (with or without increased synthesis)
Background: Underlying Thyrotoxicosis: undiagnosed or a known patient of thyrotoxicosis
Precipitating factors: Thyroid storm is precipitated by the following factors in individuals with thyrotoxicosis:
Sepsis RAI therapy
Surgery Noncompliance with antithyroid medications
Anesthesia induction Molar pregnancy
C/F: are due to ≥ 1 of the followings:
Hyperthyroidism: background of thyrotoxic manifestations
Hyperpyrexia
Hyperhydrosis: excessive sweating
Hyperactivity: anxiety/agitation/behavioural disturbance/confusion/convulsion/ delirium/emotional lability
Heart
● Hypertension with wide pulse pressure ● Heart rate:Tachycardia disproportionate to fever
● Hypotension in later stages with shock ● Heart Rhythm: Arrhythmia
Hyperperistalsis: Nausea, vomiting, diarrhoea, abdominal pain
Hyperreflexia
Investigations: Thyroid function test:
Low TSH level with high FT4 and FT3 indicates primary thyroid disorder
Elevated TSH with high FT4 and FT3 indicates excess TSH secretion: pituitary or nonpituitary source
Management:
Definitive:
1. Antiadrenergic drugs: Propranolol: orally or via nasogastric tube: dose based on heart rate and blood pressure
2. Antithyroid drugs: Carbimazole/Methimazole- to block further synthesis of thyroid hormones
3. Bile acid sequestrant: Cholestyramine prevents reabsorption of free Thyroxine in the gut
4. Conversion blocker: Glucocorticoids to decrease peripheral conversion of T4 to T3
5.’’Constipator”: Iodine compounds: Lugol iodine or KI: orally or via NG tube to block the release of Thyroxine
Supportive measures: ≥ 1 of the followings depending on clinical scenario
1. Supplemental oxygen 5. Heart: Antiarrhytmic
2. Ventilatory support 6. Hyperpyrexia: ice packs/cooling
3. Hypovolemia:IV fluid blankets/Paracetamol
4. Hypotension: IV fluid/vasopressors
Solitary Thyroid nodule/Thyroid nodules
A single nodule or multiple nodules of the gland- palpable or radiologically visible
Causes/types/DD….(Short Notes)
1. Benign
a. Euthyroid b. Thyrotoxic/Hypothyroid
Benign cyst Toxic adenoma
Colloid nodule Thyroiditis
Hyperplastic nodule
2. Malignant: Medullary/Papillary/Follicular/Hurthle cell Ca (and many others!!)
C/F- depends on the cause
1. Thyrotoxic- usually pts of toxic adenoma
2. Euthyroid- Cyst/colloid/malignant
3. Nodule may/may not be palpable
4. Warning signs- suspicious of malignancy
1. Accelerated growth of nodule 5. Fixity to surrounding structures
2. Another lesion that suggests a distant
metastasis 6. Family history of thyroid cancer
3. Cervical Lymphadenopathy 7. Hoarseness of voice
4. Consistency: Hard
5. Painful nodule = benign, painless can be either
Investigations/Diagnostic approach(short notes)
1. TFT- Pattern depends on type of the nodule 2. Imaging-USG/Radionucleide Scan
Thyrotoxic patternToxic adenoma/de Quervain/ Rare pts of Hashimoto 3. Histopatholgical confirmation-
FNAB/FNAC
Hypothyroid pattern- Hashimoto
Normal TFT- Malignancy/Cyst/Colloid
Treatment: Thyroid nodule TFT
Imaging: USG Thyroid
The following USG patterns suggest malignancy: infiltration into regional structures
ill-defined borders, irregular shape
depending on USG patterns microcalcifications
absence of a halo
solidity
depending on USG patterns AP to transverse diameter ratio (A/T) > 1
suspicious regional lymph nodes
High risk/suspicion of malignancy Intemediate risk Low risk benign pattern Not meeting FNA size cut off
Surgery/ FNA if > 1 cm FNA if >1.5 cm FNA if >2 cm No FNA
Cytology
Malignant Suspicious Benign Indeterminate
Surgery Surgery Follow up Repeat FNA/ Excision biopsy

Adrenal
Cortex Medulla
Hormone Neurotransmitters
Glucocroticoid Adrenal androgen Mineralocorticoid Adrenaline Noradrenaline
Cortisol Dehydroepiandrostenedione Aldosterone
Cortisol:
 Alters immunity
 BP ↑
 Bone: inhibits osteoblastic activity
 Collagen matrix: breakdown
 Diabetogenic
 Electrolyte: Na reabsorption & K excretion
 Fluid reabsorption
 Fat breakdown
Adrenal androgen: Reproductive function: musculinisation of females
Mineralocorticoid:
 Electrolyte balance: Na reabsorption & K excretion
 Fluid reabsorption
Hypothalamus: CRH/ Corticotropin releasing hormone

+ve stimulates
Pituitary ACTH/Corticotropin
Feed back stimulates
-ve Adrenal cortex
Glucocorticoid adrenal androgen
Aldosterone release
Mainly under Renin-Angiotensin- Aldosterone axis
Cushing’s syndrome
Cushing’s syndrome represents the clinical syndrome resulting from prolonged and inappropriately high exposure of
the tissues to the glucocorticoids, irrespective of the source (Endogenous or Exogenous)
Cushing’s disease refers to the hypercortisolism that results from the excessive secretion of corticotropin (ACTH) by a
pituitary microadenoma.
Causes:
Cushing’s syndrome
With Hyperadrenalism Without Hyperadrenalism
Primary Hyperadrenalism (Non-ACTH dependent) Iatrogenic: Corticosteroid therapy
 Adrenal adenoma and carcinoma
Secondary Hyperadrenalism (ACTH dependent) By far the most common cause of Cushing
Think about these pts...They are “Glucocorticotoxic” but
Pituitary disease/Cushing’s disease
“excess” hormone is coming from an “exogenous” source
 ACTH secreting adenoma …So, “Endogenous” Pituitary-Adrenal axis is suppressed
Ectopic ACTH syndrome due to the negative feedback exerted by an excess hormone
state. So, practically the only source of steroid is the
Clinical features: “exogenous” one…That’s why if this supply is suddenly cut
(most are due to excess Glucocotricod +/- Androgen) off an acute adrenal insufficiency state develops as the
Asymptomatic endogenous axis will take some days to recover
That’s why ANYBODY on steroid for > 2 weeks if steroid
OR ≥1 of the followings needs to be stopped it is done in a step down manner
Appearance: (NOT ABRUPTY) to allow the axis time to recover: this
 Face: step down is commonly called TAPERING OFF STEROID
o Moon face
o Acne
o Hirsutism in females(excess facial hair)
 Trunk: centripetal obesity: Protruberant abdomen with thin limbs
 Central fat deposition: over areas like thoracocervical spine, supraclavicular region (Buffalo hump)
Body weight: Gain
Bone: Risk of osteoporosis: Asymptomatic Spontaneuos fracture: pain/ tenderness/ deformity
BP: Hypertension
CNS:
 Abnormal mood
 Attention deficit
 Behavioural disturbance: Irritibality
 Concentration lack
 Dementia
 Depression
 Euphoria
Dermal:
 Easy brusibility
 Thinning of the skin
 Poor wound healing
 Pigmentation particularly in Pituitary dependent cases( high level of ACTH
Extremity: Proximal myopathy
Fertility: Infertility
Gynaecological: Erratic mensturation
Glycemic: high
Gastric: Gastric ulcer/Gastritis
Investigations: 1.To confirm the diagnosis & type 2. To look for any complications
1. To look for any complications
a. Blood: Elcetrolytes
Glycemic profile
b. Bone densitometry scan: to look for any osteoporosis
2.To confirm the diagnosis & type
Suspected Cushing’s
Rule out exogenous Cushing’s: H/o exogenous glucocorticoid intake
Confirm Cushing’s/Hypercortisolism
24-h urinary free Cortisol: high
Overnight Dexamethasone suppression test:
Overnight Dexamethasone suppression test:
8 am Serum Cortisol level is measured after a single dose of Oral Dexamethasone given in the night before of the test:
Nonsupressibility of cortisol below the physiological cut off range is diagnostic of Cushing’s
Type of Cushing’s: ACTH level estimation/ CRH stimulation test

Serum ACTH estimation
CRH stimulation test: measure ACTH after CRH adminn
ACTH : Low Serum ACTH : high
Non ACTH dependent cause ACTH dependent cause

Investigate adrenal Source: Pituitary/Ectopic
Adrenal imaging: CT/MRI Adrenal Pituitary imaging: CT/MRI
Ectopic source:CECT Chest/abdomen
Cortisol is secreted in a pulsatile manner with a circadian rhythmicity; therefore there is an “overlap” of similar values
between normal subjects and Cushing patients, so, basal serum cortisol is not used for the diagnosis of Cushing. Even
increased levels of morning basal serum cortisol have a low sensitivity for the diagnosis of Cushing. Although some studies
have tried to find a cut-off for basal serum cortisol in Cushing, different guidelines do not recommend its use in the
diagnosis of Cushing.
Because Pituitary- Adrenal axis inhibited by a high Glucocorticoid level so nonsupressibility of Glucocorticoid level below
the “cut off range” following an exogenous Glucocorticoid confirms “autonomous” release- but his cannot differentiate
between a Pitutary & an Adrenal disease.
Management:
Surgical management
ACTH dependent Cushing:
Pituitary tumor: Trans-sphenoidal pituitary surgery (TSS)- Excision of adenoma
Ectopic ACTH-secreting tumor: Resection if feasible
Non ACTH dependent Cushing: Adrenalectomy unilateral as in adenoma or malignancy

bilateral in case of bilateral hyperplasia
Bilateral adrenalectomy performed in bilateral adrenal nodular hyperplasia and for failed TSS need careful follow-
up with steroid replacement.
Medical management:
Indication: Drugs:
Preoperatively to control cortisol levels Adrenolytic: Mitotane
Modulate ACTH release: Cabergoline/Octreotide/Pasireotide
Surgery contraindicated/not feasible
Surgery has failed Inhibits glucocorticoid receptor: Mifepristone/Etomidate
Inhibit steroidogenesis: Metyrapone/Ketoconazole
Adrenocrotical insufficiency/ Hypoadrenalism(Underactive adrenal cortex)
Primary ACI
Immune related: slowly progressive autoimmune destruction of the adrenal cortex: Addison disease
Intra-adrenal hemorrhage
Infections:
 TB
 HIV
 Waterhouse friderichsen syndrome: fluminat aderenal failure in a case of Meningococcemia
Infiltrative: adrenal metastasis/ Hemochromatosis
Iatrogenic
Secondary ACI: ACI due to pituitary disease: Hypopituitarism: Tumor/trauma/ Iscaemic necrosis/ Irradiation
Glucocorticoid deficiency
Minerelocorticoid deficiency
Adrenal androgen deficiency
Mode of presentation: depending on the underlying disease manifestations may develop insidiously or rapidly
Clinical features
Asymptomatic
OR ≥1 of the followings
Asthenia(EXTREME weakness/lethargy)
Appearance: Tired looking
BP:
 Low symptomatic or asymptomatic
 Postural hypotension
 Severe hypotension and hemodynamic instability in cases of acute adrenal crisis
Body weight: loss
CNS: altered sensorium
Dermal: Hyperpigmentation: dark brown or black
Distribution: knuckles, elbows, knees, mucous membranes of the oral cavity (especially the dentogingival margins
and buccal areas).Sunexposed areas
Darkening/deepening of naturally pigmented ares: palmar crease, nipple, areola
Hyperpigmentation of the skin and mucous membranes often precedes all other symptoms by months to years.
It is caused by the stimulant effect of excess adrenocorticotrophic hormone (ACTH) on the melanocytes to produce
melanin. The hyperpigmentation is caused by high levels of circulating ACTH that bind to the melanocortin 1 receptor
on the surface of dermal melanocytes.
Extremity: Pigmentation
Electrolyte imbalance: Hyponatremia & Hyperkalemia
Fertility: subfertility/infertility
Physiology: Mineralocorticoide (to some extent Glucocorticoid)
Gynaecologyical
Na retention and K excretion
 Erratic mensturation
 Sparse axillary, pubic hair (due to lack of adrenal androgen)
Investigations:
Adrenocortical insufficiency(ACI) suspected
“Basic knowledge”about ACTH stimulation test
To confirm: ACTH stimulation test Measures the ability of the adrenal cortex to respond to
Cortisol level fails to show “expected/ Predictable” ACTH by producing cortisol appropriately.
rise above the physiological“cut off margin” after Pre ACTH administration: sample for Serum Cortisol level
After a single dose of IM ACTH injection
ACTH administration
Post ACTH serial blood samples are taken 30, 60, 90
minutes post ACTH administration…
ACI confirmed ”Pre & Post ACTH” serum Cortisol level is measured
To confirm type: Serum ACTH level
ACTH high ACTH low
Primary ACI (So, Investigate for “Adrenal disease”) Secondary ACI (So, Investigate for “Pituitary disease”)
CT/MRI of adrenal CT/MRI of Brain (Pituitary)

Pituitary Function test: Estimation of other Pit. Hormones
Treatment: Most of the patients need lifelong Hormone replacement

1. Glucocorticoid replacement: Synthetic Corticosteroid
Usually Hydrocortisone: dosing schedule 2/3 rd of the total dose in the morning and 1/3 rd in the evening
This is to mimic the normal/Physiological “circadian rhythm 24-hour fluctuation of cortisol levels”
2. Mineralocorticoid (Aldosterone) replacement: Often not needed as most of the synthetic glucocorticoids have
mineralocorticoid like activity. However, if required- synthetic Mineralocoritcoid- eg. Fludricortisone
Just for Information!!……Synthetic Corticosteroids( better known as “Steroid”)

Synthetic corticosteroids are exogenous analogues of naturally occurring glucocorticoids and mineralocorticoids
produced by the adrenal glands- they differ in their POTENCY
Acute adrenal crisis (Addisonian crisis)
Potentially life threatening condition due to severe adrenocortical insufficiency.
Etiopathogenesis: Can develop in either of these 3 sets of patients:
Known Adrenocortical insufficiency patients where the condition is usually precipitated by any 1 of the followings:
Inadequate replacement of Glucocorticoid
Severe “pathological” stressful conditions like Critical illness/Post-operative stress, particularly if Hormone
replacement dose has not been proportionately increased in these situations beforehand
Unrecognized/Undiagnosed cases of adrenocortical insufficiency: this can be the initial presentation
Sudden/Rapid failure of a previously healthy gland: acute adrenal Hemorrhage
C/F
Hypoadrenalism: may be a known case of- in these patients a precipitating factor must be looked for
Hypotension: Unexplained shock, usually refractory to fluid and pressor resuscitation
Hypothermia: may occur
Hypoactivity: altered sensorium
Hypoglycemic episodes (due to lack of glucocorticoid)
Hyperpigmentation: may be present
Investigation:
Diagnostic purpose:
Random Serum cortisol: Very low level is indicative of adrenal insufficiency.
ACTH stimulation test: diagnostic test- treatment SHOULD be started on the basis of suspicion pending the result
Assessment purpose: To look for any ppting factor+ biochemical disturbance associated with severe hypothyroidism
CBC
CRP
Ur+ Cr
Electrolytes: Na/K
ABG
ECG
Infection/sepsis screen: CxR/Urine R.E/M.E/C.S+ Blood C/S+ Procalcitonin
Treatment:
Definitive: Glucocorticoids in supraphysiologic or stress doses.
Dexamethasone does not interfere with serum cortisol assay and, thus, may be the initial drug of choice. However,
because Dexamethasone has little mineralocorticoid activity, fluid and electrolyte replacement are essential.
Hydrocortisone 100 mg IV every 6 hours is the preferred treatment to provide mineralocorticoid support.
Delaying glucocorticoid replacement therapy while awaiting the results of the ACTH stimulation test is inappropriate
and dangerous.
Supportive:
Aggressive fluid replacement with 5% or 10% IV dextrose or Saline
Treatment of hyperkalemia
Look for a precipitating cause and administration of empiric antibiotics is indicated.
Vasopressors (Dopamine/Noradrenaline) may be necessary to combat hypotension.
Pituitary
“bandmaster of the hormonal orchestra”, the pituitary gland synthesizes and releases various hormones that affect
several organs throughout the body
Hypothalamus
Median eminence:Trophic hormone releasing hormones Supraoptic & paraventricular nucleus: produce hormones
Via a portal venous system transport through the pituitary stalk
Stimulates Adenohypophysis Pituitary stored in Neurohypophyis
Adenohypophysis (anterior pituitary) Neurohypophysis (Posterior pituitary)

manufactures stores and releases
1. Adrenocorticotropic hormone (ACTH) (Not glandular and does not synthesize hormone)
2. Thyroid-stimulating hormone (TSH) 1.Oxytocin: 1.Labor & delivery 2. Lactation & breast feeding
3. Luteinizing hormone (LH) 2.ADH (Vasopressin): maintenance of water balance
4. Follicle-stimulating hormone (FSH)
5. Growth hormone (GH)
6. Prolactin (PRL)
1. ACTH: controls production of the adrenal gland hormones cortisol & DHEA
2. Thyroid-stimulating hormone (TSH): controls thyroid hormone production from the thyroid gland.
3. LH and FSH: control fertility in both sexes and the secretion of sex hormones estrogen and progesterone testosterone
4. Growth hormone (GH): required for growth in childhood and has effects on the entire body throughout life.
5. Prolactin (PRL): required for breast milk production.
6. Oxytocin: required during labor and delivery and for lactation and breast feeding.
7. Antidiuretic hormone (vasopressin): helps maintain normal water balance.
Pituitary dysfunction
Hypopituitarism Hyperpituitarism
Tumor Trauma Tumor: a particular hormone secreting tumor
Iscaemic necrosis
Intrapituitary hemorrhage Infiltation Irradiation
Pattern of the diseases is such that often the all the Usually secrete a single hormone Rarely secrete ≥2
hormone producing cells of the anterior pituitary hormones manifestations are due to oversecretion of a
gets affected- simultaneously or one after another. particular hormone
So often leads to Panhypopituitarism
Pituitary tumor…MECHANISM OF CLINICAL EFFECTS
Hormonally non functioning Hormonally functioning

nonsecretory benign adenomas Secretory adenomas: typically monoclonal
i.e. secrete a single hormone Rarely secrete 2 hormones
Expanding tumour Endocrinopathy:
Depending on size due to oversecretion of a particular pituitary hormone
Compressive effects
TSH: Hyperthyrodism
 Adjacent Pituitary Hypofunctionning Hypopituitarism ACTH: Cushing syndrome
 Outside Pituiatry Optic chiasm Bitemporal Hemianopia LH& FSH: Hypergonadism
 raised ICT Headache GH: Acromegaly/Gigantism
 stalk effect Hyperprolactinemia Prolactin: Hyperprolactinemia
Hyperprolocatinemia in Pituitary disease
1.PRL secreting tumor (Prolocatinoma) 2. “stalk effect “ of an expanding tumor: as the expanding tumor
compresses on the pituitary stalk hypothalamic Dopamine (which physiological inhibitor of Prolactin) cannot exert it’s
effect
Gigantism/ Acromegaly
Gigantism refers to abnormally high linear growth due to excessive Growth Hormone while the epiphyseal growth
plates are open during childhood. Acromegaly is the same disorder of excessive Growth Hormone but occurs after the
growth plate cartilage fuses in adulthood.
Causes:
GH-secreting pituitary adenomas or hyperplasia Ectopic GH secretion by nonendocrine tumors
(Common cause) Hypothalamic tumors; GHRH tumors
C/F: Acromegaly can be an insidious disease. Manifestations which may precede diagnosis by several years, can be
divided into the following groups:
 Manifestations due to excess circulating GH ( most of these “excess GH” manifestations are mediated by IGF1
 Manifestations due to local mass effects of an intracranial (Pituitary) tumor (Compressive effect)
Asymptomatic
Appearance
 Enlargement of head size: Broad head
 Frontal bossing
 Prominent supraorbital ridge
 Enlargement of the lower lip and nose (the nose takes on a triangular configuration)
 Prognathism Wide spacing of the teeth and prognathism Prognathism
 Macroglossia
Body weight: Increase (Mild to moderate obesity)
BP: may increase (Secondary hypertension)
Cardiac: Cardiomegaly: Cardiomyopathy: Cardiac failure and/or Arrhythmias
CNS: Compressive manifestations:
 Raised ICT: headache/vomiting/papilloedema
 Optic chiasm: Bitemporal Hemianopia
DM
Dermal Of all the maifestations following 3 are indicator of the disease activity as
 Excessive sweating these 3 become stationary and regress once GH overproduction stops
 Hypertrichosis 1. BP
2. DM/Hyperglycemia
 Oily Doughy-feeling skin
3. Skin changes
 Acanthosis nigricans
 Noticeably large pores
Extremity
 Exaggerated growth of the hands and feet, with thick fingers and toes
 carpel tunnel syndrome
Fertility
Gynaecology
Gigantism:Tall stature
Galactorrhoea due to hyperprolactinemia: Either due to 1.GH secreting tumors occasionally cosecrete Prolactin
Gynaecomastia 2. “Stalk effect” of the expanding tumor
Hoarse voice
Investigations:
1. Screening test: IGF-I: high; because of an excellent correlation between serum IGF-I levels and 24-hr GH secretion.
2. GH estimation following Oral glucose load: Because GH secretion is inhibited by Glucose, so nonsupressibility of
GH level below a cut off range following glucose confirms “autonomous” release.
(Random GH measurements, however, often are not diagnostic, because of the episodic secretion of GH, its short half-life, and the
overlap between GH concentration in individuals with acromegaly and individuals without the condition.)
3. Prolactin level: often high as pituitary adenomas co-secrete prolactin. However, a rise in prolactin may result from
stalk compression.
4. Pituitary adenomas may be associated with deficiencies of other pituitary hormones: so evaluation of the adrenal,
thyroid, and gonadal axis is important.
Imaging:
MRI of Pituitary: Because of the relatively high incidence of nonfunctioning, incidentally discovered pituitary
adenomas, imaging studies should be obtained only after a firm biochemical diagnosis of has been made.
CT scans: If MRI of the Pituitary does not show a tumor - CT chest/abdo to look for a nonpitutary tumor which can
be the source of ectopic secretion of GH
Treatment: No single treatment modality consistently achieves control of GH excess.

Pituitary adenoma:
Transsphenoidal surgery to completely remove the tumor is the treatment of choice, and it may be curative.
Medical management and/or Radiation: when Surgery not feasible/fails to remove the tumor completely
Pharmacologic Therapy:
 GH inhibitors: Somatostatin analogues: Octreotide Lanreotide, and Pasireotide
 GH receptor antagonists: Pegvisomant
 Dopamine-receptor agonists: Bromocriptine, Cabergoline
Radiation Therapy: Local Irradiation
Hypoptuitarism
Sheehan syndrome (“Pituitary crisis”)
Acute hypopiturasim following severe Postpartum hemorrhage.
Pathogenesis
Excessive blood loss during or after delivery may cause inappropriate vasospasm leading to severe ischaemia and in
such circumstances the pituitary cells may be damaged or die (necrosis).
(During pregnancy the pituitary gland will enlarge and may double in size. At this time hyperplastic gland is especially
vulnerable to "shock" and excessive maternal bleeding may induce the "shock" and the damage to the cells of the gland.
There appear to be two forms of the disorder; a chronic form and an acute form, depending on the amount of damage to the gland's
cells. The acute form reflects considerable damage so that symptoms become apparent soon after delivery. In chronic cases, the
volume of damage is much less and symptoms may not appear for months or years after delivery.)
Signs & Symptoms
1. H/O severe post partum haemorrhage
2. Refractory hypotension (adrenocortical failure) even after adequate volume resuscitation+ recurrent hypoglycemia
3. If the patient survives followings start to appear due to failure of Pituitary & “Pituitary dependent” glands:
 Failure of lactation after a woman has a baby(Prolactin deficiency)
 Menstruation does not begin again( gonadal hormone deficiency)
 Hypothyroidism: fatigue, dry skin, constipation, weight gain, sluggishness
 Adrenocortical insufficiency: fatigue, chronic hypotension, libido diminished, sparse axillary/pubic hair
 GH deficiency: Weakness, weight loss, loss of muscle strength
Investigations: Pituitary function test: Thyroid function/Adrenal function/Gonadal hormone level estimation
Treatment: Hormone replacement:
Ovarian hormone: Estrogen/Progesterone
Thyroid hormone: Thyroxine
Adrenocortical hormones: Hydrocortisone or prednisone are generally used to replace ACTH and cortisol
Growth hormone (GH) replacement therapy
Diabetes Insipidus
Diabetes insipidus (DI) is defined as the passage of large volumes (>3 L/24 hr) of dilute urine (< 300 mOsm/kg)
Types & causes:
Central Diabetes Insipidus (Neurogenic): It is due to abnormality of ADH or AVP.
Any disturbance or injury of the hypothalamus and/or posterior pituitary is a potential cause
 Tumors  Infiltration: granulomatous diseases
 Trauma  Idiopathic
Nephrogenic Diabetes Insipidus due to nonresponse of kidneys to ADH.
 Congenital
 Acquired: hypercalcemia, Lithium therapy, AKI and advanced CKD.
(Primary Polydipsic Diabetes Insipidus: It occurs due to suppression of ADH by excessive fluid intake:
 Psychogenic
 Iatrogenic DI—excessive water drinking is prescribed as a treatment
Gestational Diabetes Insipidus: It occurs in pregnancy due to destruction of ADH by placental vasopressinase.
Gestational DI and primary polydipsia (dipsogenic DI); both are caused by deficiencies in AVP, but the deficiencies do not result
from a defect in the neurohypophysis or kidneys)
Clinical features: The predominant manifestations of DI are:
Polyuria: The daily urine volume is relatively constant for each patient but is highly variable between patients (3-20 L)
Polydipsia
Nocturia
Dehydration
Investigations:
Confirmatory test: Water deprivation test:
In healthy individuals, water deprivation leads to a urinary osmolality that is 2-4 times greater than plasma
osmolality. The time required to achieve maximal urinary concentration ranges from 4-18 hours.
In central and nephrogenic DI, urinary osmolality will be less than 300 mOsm/kg after water deprivation.
After the administration of ADH, the osmolality will rise to more than 750 mOsm/kg in central DI but will not rise at
all in nephrogenic DI.
Treatment
Supportive: When oral intake is inadequate and hypernatremia is present, provide fluid replacement
Definitive: Desmopressin: 1-desamino-8-D-arginine Vasopressin (DDAVP): A synthetic analogue of ADH with
potent antidiuretic activity but no vasopressor activity
 Intranasal solution/ Intranasal spray: commonly used
 Parenteral for IV/IM injections/ Oral tablets: rarely used.
Parathyroid
In the nonpathologic state, PTH secretion enhances Ca 2+ absorption from gut and kidney and stimulates osteoclastic
bone resorption (transfer of calcium from bone fluid to the blood).
Hyperparathyroidism
Overproduction of parathyroid hormone (PTH) by one or more abnormal parathyroid glands.
Types:
1.Primary hyperparathyroidism: Hyperfunctioning of the parathyroid glands themselves due to an intrinsic disease.
Oversecretion of PTH due to a 1.Parathyroid adenoma 2. Parathyroid hyperplasia 3. Parathyroid carcinoma (RARE)
2.Secondary hyperparathyroidism is due to physiological (i.e. appropriate) secretion of parathyroid hormone (PTH) by
the parathyroid glands in response to hypocalcemia. The most common causes are vitamin D deficiency and CKD
(Lack of vitamin D – reduced Ca absorption by the intestine – hypocalcemia - increased parathyroid hormone secretion. In CKD -
failure to convert vitamin D to active form in the kidney. The bone disease in secondary hyperparathyroidism caused by renal
failure is termed renal osteodystrophy).
3.Tertiary hyperparathyroidism is seen in patients with long-term secondary hyperparathyroidism which eventually
leads to hyperplasia of the parathyroid glands and a loss of response to serum calcium levels i.e the gland becomes an
autonomous one.
Clinical features:
1.“hypercalcaemic” symptoms can include:
A- Appetite loss D- dehydration
Abdominal cramp/ pain E- Excessive thirst
B- Bodyache- joint/muscleache Emesis
C- Constipation F- Fatigue
Confusion Frequent urination
Convulsion
2. Potential Dangers of “missed” or untreated Primary Hyperparathyroidism:
• Bone fractures: Osteoporosis and osteopenia
• Kidney stones
• Peptic ulcers
• Pancreatitis
• Nervous system complications: Psychosis/depression/dementia
Investigations:
Blood:
Serum Ca 2+ - elevated serum calcium
serum PTH concentration- “inappropriately” elevated
Serum urea and creatinine (to assess kidney function)
Serum PO4 3- - Normal/Low/high
Urine test – 24 Hour urine calcium (to exclude a rare condition familial hypocalciuric hypercalcaemia)
Imaging:
1.USG abdomen: imaging of the kidneys (to exclude stone formation)
Imaging of the pancreas (to exclude pancreatitis)
2.Skeletal X-Rays and Bone densitometry scan (DEXA scan)- To determine the detrimental effect of prolonged PTH on
the skeleton.
3.Parathyroid imaging with Technetium 99m SESTAMIBI scan – This is a radiolabelled nuclear medicine scan of the
thyroid that preferentially localises a single abnormal parathyroid adenoma that may be amenable to minimally
invasive parathyroid surgery.
Treatment
Primary Hyperparathyrodism
1. Definitive treatment: Surgical excision of the abnormal parathyroid glands
2. Supportive treatment: Management of severe hypercalcemia in the acute setting
 a.Short term/ Emergency treatment: in case of dangerous hypercalcemia/symptomatic hypercalcemia
a.IV fluid: intravascular volume expansion with sodium chloride
b.Loop diuretics: Furosemide once the intravascular volume is restored.
c.Drugs: Calcitonin and IV bisphosphonate as a temporary measure prior to surgery
 b. Long term treatment:
1.Bisphosphonates: Alendronate/Risedronate/Zolendronate, has been shown to improve the Bone Mineral
Density(BMD) in patients with primary hyperparathyroidism. Treatment with a bisphosphonate can be considered in
patients with hyperparathyroidism and low BMD who cannot, or will not, undergo surgery.
2.Calcimimetic drug: Cinacalcet activates the calcium-sensing receptor and inhibit parathyroid cell function.
Cinacalcet results in reduction of PTH levels, reduction and even normalization of serum calcium.
Secondary hyperparathyroidism: treat the cause/ effects

1.CKD: 1.Phospate binders 2.Vitamin D supplementation 3.Calcimimetic
2.Vitamin D deficiency: Vitamin D supplementation
Hypoparathyroidism
Underactivity of the Parathyroid glands with underproduction of Parathyroid hormone.
Hypoparathyroidism can have the following causes: “ 5 I”
1. Iatrogenic: Inadvertent injury to the glands or their blood supply during thyroidectomy/parathyroidectomy or
other surgical interventions in the central part of the neck- inadvertent injury to the glands or their blood supply is still
common. When this happens, the parathyroids may cease functioning. This is usually temporary but occasionally long
term (permanent).
2. Immunological: Autoimmune invasion and destruction- occur as part of Autoimmune Polyendocrine syndromes.
3. Infiltrative: Hemochromatosis
4. Inherited: Atrophied or absent parathyroid glands
5. Insufficient Mg: Magnesium depletion causes relative PTH deficiency and end-organ resistance to PTH action
Clinical features: mainly Hypocalcemic manifestations:

1. Muscle cramps involving the back and legs.
2. Insidious hypocalcemia may cause mild encephalopathy and should be suspected in patients with unexplained
dementia, depression, or psychosis.
3. Tetany characteristically results from severe hypocalcemia but can result from reduction in the ionized fraction of
serum calcium without marked hypocalcemia, as occurs in severe alkalosis. Tetany is characterized by the following:
Sensory symptoms consisting of paresthesias of the lips, tongue, fingers, and feet
Carpopedal spasm, which may be prolonged and painful
Generalized muscle aching
Spasm of facial musculature
Tetany may be overt with spontaneous symptoms or latent and requiring provocative tests to elicit-
Chvostek sign is an involuntary twitching of the facial muscles elicited by a light tapping of the facial nerve just
anterior to the exterior auditory meatus.
Trousseau sign is the precipitation of carpal spasm by reduction of the blood supply to the hand with a tourniquet or
BP cuff inflated to 20 mm Hg above systolic BP applied to the forearm for 3 min.
Investigations: 1.Serum Ca: typically Low 2. Serum PTH: Low
Treatment: 1. IV Calcium- Ca-Gluconate or Oral Ca-Carbonate 2. Recombinant Parathyroid hormone:Teriparatide
Diabetes Mellitus
Syndrome characterized by inappropriate hyperglycemia with an absolute or relative deficiency of insulin secretion
World Health Organization (WHO) criteria:

 Fasting plasma glucose (FPG) ≥ 126mg/dl
and/or
 Oral glucose tolerance test (OGTT) with 75 gms of anhydrous glucose: 2 hours post plasma glucose ≥ 200 mg/dl
and/or
 Glycated haemoglobin (HbA1c) ≥ 6.5%
and/or
 Random plasma glucose ≥ 200mg/dl in the presence of classical diabetes symptoms
NB:
Asymptomatic individuals with a single abnormal test should have the test repeated to confirm the diagnosis unless
the result is unequivocally abnormal.
FPG is defined as glucose estimated after no caloric intake for at least 8-12 hours
Types/Classification
1. Type 1 diabetes: due to autoimmune β-cell destruction, usually leading to absolute insulin deficiency
2. Type 2 diabetes: due to a progressive loss of β-cell insulin secretion frequently on the background of insulin
resistance
3. Gestational diabetes mellitus (GDM): diabetes diagnosed in the second or third trimester of pregnancy that was not
clearly overt diabetes prior to gestation
4. Specific types of diabetes due to other causes:
Neonatal diabetes
Maturity-Onset Diabetes of the Young [MODY]
Secondary diabetes:
Secondary Diabetes: DM that results as a consequence of another medical condition.
Chronic Pancreatic disease: Diseases of the exocrine pancreas – Chronic Pancreatitis/ Cystic fibrosis
Drug induced: Corticosteroid
Endocrinopathies: Cushing syndrome/ Acromegaly/Pheochromocytoma
Ferrous: Hemochromatosis
Type 1 Diabetes: Insulin dependent Diabetes/Juvenile onset Diabetes
a. Immune Mediated Diabetes (Type 1a): results from a cell mediated autoimmune destruction of the beta cells of the
pancreas. Autoantibodies associated with the T1DM are islet cell autoantibodies (ICA), antibodies to insulin (IAA),
antibodies to glutamic acid decarboxylase (GAA or GAD) and protein tyrosine phosphatase (IA2 or ICA512)
b. Idiopathic Diabetes (Type 1b): Some forms of type 1 diabetes have no known etiologies. Some of these patients have
permanent insulinopenia and are prone to ketoacidosis, but have no evidence of autoimmunity. Only a minority of
patients with type 1 diabetes fall into this category.
Type 2 diabetes:
Results from predominantly insulin resistance with relative insulin deficiency. This form of diabetes frequently goes
undiagnosed for many years because hyperglycemia develops gradually and in earlier stages is often not severe
enough for the patient to develop any of the hyperosmolar symptoms of diabetes. Nevertheless such patients are at an
increased risk of developing macrovascular and microvascular complications and these may be present even at the
time of diagnosis. However, in the course of time they also become Insulinopenic & are likely to require insulin for
better glycemic control.
Clinical fetaures/clinical Assessment of diabetes Patient:
Aims:
1. To look for Hyperglycemic manifestations
2. To look for metabolic symptoms
3. To look for any complication: these may be present on first presentation or may develop later
4. To look for any other Atherosclerotic(Vasculopathic) Risk factors
5. Dietary & drug compliance
6. To look for any secondary causes of DM
1. Hyperglycemic symptoms:
 h/o Polyuria  Visual disturbances
 h/o Polydipsia  Balanitis/balanoposthitis/vulvovaginitis/vaginiti
 h/o Polyphagia s: Genital itching/irritation
 Delayed healing of ulcers
2. Metabolic symptoms
 h/o Weight loss: often RAPID and SIGNIFICANT
 h/o generalized weakness
3. Symptoms suggesting development and severity of complications:
a. Macrovasculopathy:
1. Cerebrovascular disease:
 h/o TIA/CVA
2. Coronary artery disease:
 h/o Angina/ MI
3. Peripheral vascular disease
 h/o Claudication
 h/o gangrene
 h/o amputation
b. Microvasculopathy:
1. Nephropathy (Kidney disease):
 h/o swelling: Any Facial puffiness/Any Pedal edema
 h/o decreased urine output
 h/o breathlessness
2. Neuropathy:
1. Sensory Neuropathy:
 h/o Sensory impairment: altered sensation or painful feet or arm
 Foot ulcers
2. Autonomic neuropathy
 Bladder: h/o incontinence
 Gastrointestinal function: h/o Constipation/ flatulence
 Symptoms of Orthostatic hypotension: Portural dizziness/ black out
 Erectile dysfunction
3. Retinopathy:
 h/o retinopathy
 Any visual disturbance
4. Risk factors for atherosclerosis:
 Activity status: exercise lack  Cigeratte smoking
 BP: Hypertension  Dyslipidemia
 BMI: obesity  Family history: atherosclerotic disease
 Current nutritional status  Current treatment and glycemic status:
 Eating pattern medications, compliance
6. Evaluation for possible causes of secondary diabetes mellitus.
Examination: Important findings with their clinical relevance:
 Arterial pulse: poor peripheral pulses: Peripheral vascular disease
 BMI: atherosclerotic risk factor
 BP: risk factor
 BP: Lying and standing: Postural drop: Autonomic neuropathy
 Cardiac: Gallop/Basal crackles: heart failure
 CNS: focal neurodeficit: CVA/TIA Sensory impairment: Neuropathy
 Edema: CKD/CCF
 Eye: Fundoscopy: To look for retinopathy: ophthalmoscopic evaluation by ophthalmologist
 Foot: Ulcer/gangrene/cellulitis: Neuropathy/ Peripheral vascular disease
Investigations:
1. To confirm DM
2. Glycemic control monitoring: frequency of monitoring depend on glycemic status
3. To look for complications: Exact nature and frequency of these tests depend on presence/absence of complications,
however some of the tests are monitored even if clinically no evidence of complications are there.
4. To look for any other Atherosclerotic (Vasculopathic) Risk factors
1. To confirm DM & Glycemic monitoring: Blood: FBG, PPBG, HbA1c
Diagnostic criteria for diabetes: Any 1 of these
Plasma Glucose Normal Imapaired Diabetes
Fasting < 110 mg/dl > 110 mg/dl but ≤ 125 mg/dl ≥ 126 mg/dl
OGTT (Post prandial) < 140 mg/dl > 140 mg/dl but ≤ 199 mg/dl ≥ 200 mg/dl.
HbAIc < 5.7 % 5.7%- 6.4% ≥6.5%
Random BG ≥200 mg/dL with classic symptoms of hyperglycemia or hyperglycemic crisis
In fasting state, venous and capillary glucose are the same, but it differs in the PP state.
Glycemic monitoring: Target/ Criteria Glycemic Control

Target values for glucose control for HbA1c and capillary plasma glucose are as follows:
HbA1c < 7.0 %
FPG < 115 mg/dl
PPG < 160 mg/dl
To look for complications: Exact nature and frequency of these tests depend on presence/absence of complications,
1. CBC: Hb, TC,DC, ESR
 Hb: Low: may be due to CKD
 TC,DC, ESR: high: infection
2. Serum urea creatinine: raised: CKD
3. Urine analysis: To assess Albumiuria
 Urine dipstick analysis: Proteinuria
 Urinary Microalbumin- Creatinine ratio( MACR): To assess Albumiuria
4. ECG
5. Echocardiography
To look for any other Atherosclerotic (Vasculopathic) Risk factors: Blood: Lipid profile
Special tests: ONLY indicated if a particular complication is suspected
Suspected complication Relevant investigations
Coronary artery disease Exercise tolerance test/Tread mill test(TMT)/Myocardial perfusion
scan/Angiography
Cerebrovascualr disease CT Brain/ Carotid Doppler
Peripheral vascular disease Doppler study of peripheral arteries/Peripheral angiography
Neuropathy Nerve conduction study(NCS)/NCV
Treatment:
Treatment of DM
Glycemic control Treatment of complications Treatment of atherosclerotic risk factors (if present)
depends on complication(s) Activity status: exercise lack
Lifestyle Pharmacotherapy BP: Hypertension
modification 1.Oral hyoglycemics BMI: obesity 1. Lifestyle
modifin
1. Diet 2. Insulin Cigeratte smoking 2. Drugs
2. Exercise Dyslipidemia
Glycemic control
Lifestyle modification:
A. Diet:
1. Energy (calories): 25-30 cal/kg IBW - reduce in obese and increase in underweight
2. Protein 0.8 g/kg body weight.
3. Fats: 20-25% of total calories
4. Carbohydrates: 55-60% of total calories. Encourage complex carbohydrates i.e. mainly grains, cereals, pulses.
B. Exercise: Regular physical exercise
Pharmacotherapy/Medications:
1. Oral Hypoglycemic agents (OHAs)/Oral Antidiabetic drug (OAD)
1. Increasing insulin secretion:
 Sulfonylureas(SU): Glimepiride/Gliclazide/Glyburide
 Meglitinide analogs: Repaglinide/Mitiglinide
 D-Phenylalanine derivative: Nateglinide
2. Reduction of insulin resistance (Insulin sensitisers): Thiazolidinediones (TZD): Pioglitazone/ Rosiglitazone
3. Reduction of hepatic glucose output: Biguanides: Metformin
4. Reduced carbohydrate absorption: Alpha glucosidase inhibitors(AGI): Voglibose/Acarbose
5. Incretins:
GLP1 receptor agonist: Exenatide/Liraglutide/Lixisenatide
DPP-4 Inhibitors (Gliptins): Vidagliptin/Linagliptin/Saxagliptin
6. SGLT 2 inhibitors: Canaglifozin/Dapaglifozin/ Empagliflozin
2. Insulin
Basal insulin is the background insulin that is normally supplied by the pancreas and is present 24 hours a day,
whether or not the person eats.
Bolus insulin refers to the extra amounts of insulin the pancreas would naturally make in response to glucose taken in
through food.
Types:
Short acting: 1.Regular
Rapid acting: 1. Aspart 2. Lispro 3. Glulicine
Intermediate acting: Neutral protamine hagedorn (NPH)
Premixed: Intermediate acting Insulin + Short/Rapid acting Insulin: 70:30/ 75:25/ 50:50
 NPH+ Regular
 Insulin aspart protamine suspension + Insulin aspart
 Insulin Lispro protamine suspension + Insulin Lispro
Long acting 1.Glargine 2. Detemir 3. Degludec
Intemediate/Long-acting “basal” insulins begin working in 1-2 hours but are released slowly so they can last up to 24
hours, providing that background insulin that is needed around the clock.
Fast-acting “bolus” insulins generally begin working within 15-30 minutes. Each of these bolus insulins is designed to
be taken just before a meal and have a duration of up to 5- 6 hours, so they counteract postprandial glycemic surge
Hyperglycemia: drug strategy
Start Glucose lowering medications when lifestyle interventions alone are unable to maintain/achieve target glucose
Lifestyle measures to continue throughout the use of these medications
Consider a new agent or dose increase of a medication with “ SUGAR”monitoring every 2-3 months
Choice of drug (s) depend on following factors:
Age Duration of Diabete
BMI Duration of DM
Complications Education status about Diabetes
Contraindication Financial condition
Glycemic status Hypoglycemia risk
Type of DM
Type 1 DM Type 2 DM: depending on GLYCEMIC control

Insulin: 1. OHA only 2. OHA + Insulin 3. Insulin only
Basal Regime: Long acting Insulin
+ OHA(s): usually a Single OHA is started
Bolus regime: Short/Rapid acting Insulin Dose increase or add a new agent depending on response every 2-3 m
Glucose lowering effect:
 High: Metformin, SU, TZDs, GLP-1 agonists
 Comparatively lower: Meglitinides, DPP-4(-)ors, SGLT2(-)ors,AGI
Insulin:
 Basal insulin once daily: NPH or Glargine or Detemir
 Once or twice daily Premix insulin (biphasic insulin)
Indications of Insulin therapy in DM
1. Type 1 DM- ALL patients
2. Type 2 DM
Long term Insulin treatment
In newly diagnosed patient: at the time of diagnosis are symptomatic and have one of the following: –
 HbA1C more than 9%
 Fasting hyperglycemia in excess of 250 mg/dl
 Post prandial hyperglycemia in excess of 300 mg/dl
 In catabolic stage
In patients with already established diagnosis:
 If a trial of adequate doses of three non-insulin agents for 6-9 months fails to achieve HbA1c to target levels
 Presence of contraindications preclude use 1 or >1 OHAs
Short term insulin therapy
1. All diabetics with Acute metabolic complications- DKA/HHS (HONC)
2. All diabetics admitted during a critical illness- eg. Sepsis/stroke/MI
3. All diabetics- To achieve glycemic control during pre/intra and post oprve period (depending on the type of surgery)
Complications of DM
1. Acute- those develop over hours- days 2. Chronic- those develop over years
a. Metabolic complications-
a. DKA a. Macrovasculopathy
b. HHS a. Cerebrovascular disease
c. Hypoglycaemia b. Coronary artery disease
b. Acute presentation of a chronic complication c. Peripheral vascular disease
a. CVC/TIA b. Microvasculopathy
b. Myocardial Ischaemic event a. Retinopathy
c. Acute ischaemic limb b. Neuropathy
c. Nephropathy
Diabetic Retinopathy
It is an ocular manifestation of diabetes which affects most of the DM patients who have had diabetes for ≥20 years
C/F
Initial stages- generally asymptomatic
Advanced stages- floaters, blurred vision & progressive loss of visual acuity
Signs of diabetic retinopathy:
Stages
1. Nonproliferative diabetic retinopathy
Presence of microaneurysm(s)-due to capillary wall outpouching
Dot and blot hemorrhages- due to microaneurysms rupture
Hard exudates- due to leakage of serum lipids and proteins from the vessels
Cotton-wool spots: due to infarctions from occlusion of arterioles
2. Proliferative diabetic retinopathy- can be vision threatening
Neovascularisation: hallmark of PDR
Pre retinal hemorrhages: pockets of blood within the space between the retina and the posterior hyaloid face
Vitreous hemorrhage
Retinal detachment
3. Maculopathy- Can occur at any stage
Macular Oedema
Investigations
1. Glycemic assessment- FBS/PPBS/HbA1c
2. Fundus Fluorescein angiography (FFA)
3. Optical coherence tomography (OCT)
Treatment:
a. Strict/ Tight Glycaemic control
b. Ophthalmological Rx- Urgent referral IF PDR or Maculopathy OR impaired vision
1. Pharmacotherapy
Triamcinolone: Administered intravitreally
Bevacizumab/ Ranibizumab: Administered intravitreally- reduces macular edema and neovascularization
2. Laser photocoagulation- Panretinal photocoagulation is used in the treatment of PDR.
3. Regular Ophthalmological screening- FOR ALL DIABETICS starting 6-8 years after the onset of DM
Diabetic Neuropathy
Diabetic neuropathy is the most common complication of diabetes mellitus (DM), affecting as many as 50% of patients
with type 1 and type 2 DM
Types
Sensory Neuropathy- commonest type
Numbness or deadness- typically in distal part of the extremities
Loss of balance- especially with the eyes closed
Painless injuries due to loss of sensation
Painful Neuropathy- burning/prickling/tingling/electric shock like feelings
Peripheral neuropathy can lead to foot ulcers and leg amputation
Foot ulcer shows signs of infection- thick yellow exudate + erythema + fever + necrotic tissue
O/E impaired superficial + deep sensation in the distal part of the extremity to start with (Glove and stocking)
Motor Neuropathy
Distal or proximal or more focal weakness
LMN signs in the distribution of the affected nerve(s)
In the most common presentation of diabetic neuropathy with symmetrical sensorimotor involvement Sensory loss+
minor weakness of the toes and feet may be seen; severe weakness is uncommon
Autonomic neuropathy- may involve
Cardiovascular- Sinus tachycardia/Orthostatic hypotension/Sinus arrhythmia/Syncope or Presyncope
Gastrointestinal- Abdominal pain/Bloating/ Constipation/ Diarrhoea/Emesis/ Fecal incontinence
Genitourinary- Poor urinary stream/Feeling of incomplete bladder emptying/Straining to void/Erectile Dysfunction
Investigations
Glycaemic assessment- FBG + PPBG+ HbA1c
For Neuropathy- Electrophysiological tests - NCV & EMG
Imaging studies- MRI of the Cervical and/or Thoracic and/or Lumbar regions may help to exclude another cause for
symptoms mimicking diabetic neuropathy.
Management
1. Awareness- patient to be made aware of potential foot complication
2. Foot care- regular foot examinations
3. If necessary, refer the patient to a podiatrist.
4. Infected diabetic foot ulcer or gangrene
 Antibiotic
 Antiseptic dressing
 Surgical Debridement
 Amputation
5. Painful Neuropathy- Gabapentin/ Pregabalin/Amitryptiline
6. Erectile dysfunction- Phosphodiesterase type 5 (PDE5) inhibitors- Sildenafil/Tadanafil
7. Orthostatic hypotension
 Increase dietary fluid and salt intake
 Compression stockings may help
Diabetic Foot
Complication arising due to compromise of the blood supply from macrovascular disease often in association with
lack of sensation because of neuropathy.
C/F- Predisposes persons with DM to foot infections.
Signs and symptoms
1. Peripheral Vascular disease related manifestations
 Claudication/Poor distal pulses/ severe cases ischaemic ulcer
2. Peripheral Neuropathy related manifestations
 Numbness or deadness- typically in distal part of the extremities
 Loss of balance- especially with the eyes closed
 Painless injuries due to loss of sensation
 Painful Neuropathy- burning/prickling/tingling/electric shock like feelings
3. Diabetic foot infections typically take one of the following forms
 Neuropathic ulcers +/- secondary infection
 Cellulitis- Tender, erythematous skin
 Deep skin and soft-tissue infections- painful induration of the soft tissues in the extremity Wound discharge is
usually not present
 Osteomyelitis- pain at the site of the involved bone. Deep, penetrating ulcers and deep sinus tracts are usually
located between the toes or on the plantar surface of the foot.
Investigation
1. TC, ESR/CRP- elevated if infection 3. Blood culture results may be positive
2. Aspirated exudate- gram stain/CS 4. Osteomyelitis- X-ray
5. US Doppler +/- Peripheral Angiography- for Ischaemic limb
Management- Treatment of diabetic foot infections varies by type
1. Cellulitis – antibiotics
2. Deep skin and soft-tissue infections – Antibiotic but additional debridement is usually indicated
3. Osteomyelitis – Antibiotic
Surgical debridement is essential
Amputation- if necessary
4. Ischaemic limb- Amputation, if necessary
Diabetic Nephropathy
Syndrome characterized by persistent albuminuria +/- Progressive decline GFR +/- Elevated BP
C/F
1. Edema secondary to hypoalbuminemia
2. Features of CKD
4. Patients may have physical findings associated with long-standing diabetes mellitus like
 Hypertension  Evidence of diabetic neuropathy
 Peripheral vascular occlusive disease  Evidence of DM Retinopathy
Investigations
1. 24-hour urinalysis/Urinary ACR: Microalbuminuria or Macroalbuminuria
2. Blood- Urea, Cr, FBG, PPBG, HbA1c
3. USG KUB- For kidney size- normal to increased in the initial stages & later shrunken with CKD.
4. Renal biopsy is not routinely indicated.It is indicated if the diagnosis is in doubt or if other kidney disease is
suggested.
Treatment
Tight Glycaemic control Tight control of Dyslipidemia
ACE-i/ARB Supportive treatment for CKD- if established CKD
Tight BP control
HbA1c
Haemoglobin A1c (Glycated Hb) reflects the average blood glucose concentration over the course of the RBC lifespan,
roughly 120 days in normal individuals. It provides different but complementary information to a single glucose
concentration.
Values for DM diagnosis Values for DM/Glycaemic control

Normal- 4% and 5.6%. Ideal control < 7%
Increased risk of DM/Impaired GTT- 5.7% and 6.4% Average control 7- 7.9%
Diabetic ≥ 6.5% Bad control ≥ 8%
Pitfalls
HbA1c is usually a reliable indicator of DM diagnosis & Glycaemic control except:
Patients with symptoms of diabetes for less than two months
Patients at high diabetes risk who are acutely ill
Patients taking medication that may cause rapid glucose rise- eg. steroids, antipsychotics.
Patients with acute pancreatic damage, including pancreatic surgery
Pregnancy
Presence of other factors that influence HbA1c and its measurement:
 Situations where the RBC lifespan is significantly less than 120 days will give rise to low HbA1c
Increased red cell turnover: blood loss, hemolysis, haemoglobinopathies
OHA/OAD
There are 5 categories of OHAs/OADs
1. Increase sensitivity to insulin (ISAs- Insulin-sensitizing agents) + Decreased Hepatic Glucose output
 Metformin
 Thiazolidinediones: Rosiglitazone; Pioglitazone
2. Provoke Pancreas to produce more Insulin (Secretagogue)
 Sulfonylurea: Glimepiride; Glipizide; Gliclazide; Glibenclamide; Glyburide
 Meglitinides: Repaglinide; Nateglinide
3. Incretin like effects: Dipeptidyl peptidase IV inhibitors (DPP4 –tors):
 Vidagliptin/Sitagliptin/Linagliptin/Saxagliptin
 GLP-1 analogues- Exenatide; Liraglutide
4. Inhibits Intestinal Glucose absorption: α-glucosidase inhibitors: Voglibose; Acarbose
5. Inhibits Renal Glucose absorption: Inhibitor of Sodium-Glucose Linked Transporter (SGLT)
 Canagliflozin; Dapagliflozin; Empagliflozin
Indications of OHA- Type 2 DM- either a single agent or combination of drugs
The choice of the OHA(s) depend on following factors
Age
BMI
Complications
Contraindication
Duration of Diabetes
Education status about Diabetes
Financial condition
Glycemic status
Hypoglycemia risk
DKA…..V. Important
Diabetic ketoacidosis (DKA) is an acute, potentially life-threatening metabolic complication of diabetes characterized
by hyperglycemia, ketoacidosis, and ketonuria that mainly occurs in patients with Type1DM and rarely in Type 2DM.
Background of the patient- Pts are usually a Ty 1 DM pts- hitherto (until now) undiagnosed or a known case.
Precipitating Factor- May be present and if present usually is one of these
1. Missing dose(s) of Insulin 3. Critical Illness
2. Infection
Pathophysiology Severe Insulin deficiency + ↑counter-regulatory hormones (Glucagon/GH/cortisol)
↑↑hepatic gluconeogenesis + glycogenolysis + ↑↑lipolysis
severe hyperglycemia increased serum free fatty acids
polydipsia and polyuria Glucosuria ketogenesis (acidic intermediate)
osmotic diuresis ketogenesis (acidic intermediate)
dehydration Ketonemia + Ketonuria
accumulation of organic acids
metabolic acidosis (ketoacidosis)
Therefore main problems in DKA are-

2. Dehydration 5. Abnormally high Glucose level
3. Ketoacidosis/Ketonemia 6. Associated ppting factor (if any)–Infn/illness
4. K- imbalance
Hyperkalemia: Often present initially & is caused by a shift of potassium from the intracellular to the extracellular
space in an exchange with hydrogen ions that accumulate extracellularly in acidosis + due to insulin deficiency.
Much of the shifted extracellular potassium is lost in urine because of osmotic diuresis.
Hypokalemia: As these patients get started on IV Insulin, K gets rapidly shifted into cells (Ex.cellular to In.cellular)
Symptoms
1. May be a known case of Ty-1 DM or undiagnosed DM- therefore may give recent h/o Wt. loss+/-Polyphagia +/-
Polyuria- these are due to underlying DM
2. Dehydration related manifestations
 Altered sensorium  Dry mucous membranes
 BP: Hypotension  Decreased skin turgor
 CRT: prolonged  Extremity:Tachycardia
 Disorientation  Excess thirst
 Dry skin
3. Ketonemia/ Ketoacdisis related manifestations
 Nausea and vomiting  Kussmaul Breathing- Rapid, shallow breathing
 Abdominal pain  Severe Acidosis arrhythmias suddenly
 Acetone (ketotic) breath odour- Fruity smell
4. Abnormal high Glucose related manifestations-
 Polyuria/Polydipsia/Polyphagia
5. Associated ppting factor (if any) related manifestations
 H/o missing Insulin doses recently
 Active infection- Fever/Chill+ rigor+ Symptoms of focal infection- URTI/LRTI/UTI etc.
 Any other critical illness
Investigations
Tests To look for/Aim of the test/Potential abnormality
1. CBG- ↑↑ Immediately and thereafter at regular interval
2. Hb,TC,DC,CRP- ↑TC/CRP- Infection
3. Ur,Cr- ↑- Dehydration
4. Electrolytes-Na, K, Cl Dyselectrolytemia
5. ABG Metabolic Acidosis- pH, HCO3, CO2
6. Ketone levels Ketoniemia
7. Urine Ketone Ketonuria
8. Amylase and lipase May be non-specifically high in DKA- does not suggest Pancreatitis!!
9. Sepsis screen- If febrile or infection is suspected
10. CxR/Urine- R.E/M.E/C.S/Blood C.S
Many of these tests particularly blood biochemistry are to be repeated at regular interval till pt. become stable
Management
Goals/Aims
1. Rx of Dehydration- Fluid resuscitation 3. Correction of K-imbalance- KCl
2. Reversal of the Ketoacidosis- 4. Reduction of Abnormal glucose- Insulin
 Alkalinising agent- NaHCO3 5. Rx Associated precipitating cause/factor, if any
1. Dehydration Rx- Fluid resuscitation- Rate/amount depends on volume status + cardiac and renal status
a. Initial correction either by Isotonic NaCl solution or Ringer Lactate

b. Recommended schedule for restoring fluids is as follows:
1. Administer 1-2 L during the first hour. 4. Administer 1 L every 4-6 hours, depending on the
2. Administer 1 L during the second hour. degree of dehydration
3. Administer 1 L during the following 2 hours
c. When euvolemic, switch to half Normal NaCl, particularly if hypernatremic
d. When blood sugar is ≤ 200-180 mg/dl, Isotonic NaCl is replaced with 5-10% D to prevent any hypoglycaemia
induced by Insulin infusion
2. K- imbalance- KCL infusion should be started from the beginning as Insulin will start to shift K rapidly
into cells causing Extracellular Hypokalemia- KCl is added to the infusion fluid
If K is greater than 6 mEq/L- no K supplement If K is 3-4.5 mEq/L- KCl 20 mEq/h
If K is 4.5-6 mEq/L- KCl 10 mEq/h
Monitor Potassium level regularly
3. Ketoacidosis-
NaHCO3 infusion only if decompensated acidosis starts to threaten the patient's life.
Rapid administration of NaHCO3 can cause cerebral oedema particularly in children.
4. Abnormal Glucose- Insulin Infusion- Monitor blood glucose at bedside every hour till it’s stabilized
Initially Continuous IV Short acting Insulin infusion using an infusion pump
5. Antibiotic- Empiric antibiotics on suspicion of infection
6. Anticoagulation- Prophylactic Heparin- Severe dehydration can cause hyperviscocity precipitating DVT
7. After the patient is stable further/a long term management plan of DM should be drawn up.
Hyperosmolar hyperglycemic state (HHS)…..V. Important
Hyperosmolar hyperglycemic state (HHS) is an acute, potentially life-threatening metabolic complication of diabetes
characterized by hyperglycemia, hyperosmolarity, dehydration without significant ketoacidosis & ketonuria that
mainly occurs in patients with Type 2 DM and rarely in Type 1 DM.
HHS was previously termed hyperosmolar nonketotic coma (HONC); however, the terminology was changed because
coma is found in very few pts of HHS.
Background of the patient- Pts are usually Type 2-DM pts- hitherto (until now) undiagnosed or a known case.
Precipitating Factor- May be present and if present is usually one of these

1. Missing dose(s) of Insulin/OHA 3. Critical Illness- Stroke/MI/PE/underlying
2. Infection CKD/ CHF are at increased risk
Pathophysiology Severe Insulin deficiency + ↑counter-regulatory hormones (Glucagon/GH/cortisol)

↑↑hepatic gluconeogenesis + glycogenolysis + No significant lipolysis
severe hyperglycemia No Ketonemia + Ketonuria
polydipsia and polyuria Glucosuria No metabolic acidosis (ketoacidosis)
osmotic diuresis
dehydration
(Unlike DKA, in HHS significant ketoacidosis DOES NOT occur, but the reason for this is NOT CLEAR. Contributing
factors likely include the availability of insulin particularly in Portal circulation in amounts sufficient to inhibit
ketogenesis but insufficient to prevent hyperglycemia. In addition, levels of counter-regulatory hormones like GH are
found to be lower in patients with HHS than in those with DKA.)
Therefore main problems in HHS are-

1. Dehydration 4. Abnormally high Glucose level
2. Ketoacidosis/Ketonemia- NO 5. Associated ppting factor (if any)–Infn/illness
3. K- imbalance
Hyperkalemia: Often present initially & is caused by a shift of potassium from the intracellular to the extracellular
space in an exchange with hydrogen ions that accumulate extracellularly in acidosis + due to insulin deficiency.
Much of the shifted extracellular potassium is lost in urine because of osmotic diuresis.
Hypokalemia: As these patients get started on IV Insulin, K gets rapidly shifted into cells(Ex.cellular to In.cellular)
Symptoms-HHS usually develops over a course of days to weeks, unlike diabetic ketoacidosis (DKA), which develops
more rapidly, over the course of a few days. Often, a preceding illness results in several days of increasing
dehydration.
1. May be a known case of Ty-2 DM or undiagnosed DM- therefore may give recent h/o Wt. loss+/-Polyphagia +/-
Polyuria- these are due to underlying DM
2. Dehydration related manifestations
 Altered sensorium  Decreased skin turgor
 BP: Hypotension  Extremity:Tachycardia
 CRT: prolonged  Excess thirst
 Disorientation
 Dry skin 3. K-----ABSENT
 Dry mucous membranes
4. Abnormal ↑↑ Glucose related manifestations- Polyuria/Polydipsia/Polyphagia
5. Associated ppting factor (if any) related manifestations
 H/o missing OHA dose/ Insulin doses recently
 Active infection- Fever/Chill+ rigor+ Symptoms of focal infection- URTI/LRTI/UTI etc.
 Any other critical illness
Investigations
Tests To look for/Aim of the test/Potential abnormality
1. CBG - High- Immediately and thereafter at regular interval
2. Hb,TC,DC,CRP- ↑TC/CRP- Infection
3. Ur,Cr- ↑- Dehydration
4. Electrolytes-Na, K, Cl Dyselectrolytemia
5. ABG No metabolic Acidosis- BUT may occur due to associated illness eg. sepsis
6. Ketone levels No Ketoniemia
7. Urine Ketone No Ketonuria
8. Sepsis screen- If febrile or infection is suspected
CxR/Urine- R.E/M.E/C.S/Blood C.S
9. ECG/Cardiac enzymes- if MI is suspected
10. CT Brain ( IF pt is drowsy)- to rule out CVA
Many of these tests particularly blood biochemistry are to be repeated at regular interval till pt. become stable
Management
Goals/Aims
1. Rx of Dehydration- Fluid resuscitation 3. Reduction of Abnormal glucose - Insulin
2. Correction of K-imbalance- KCl 4. Rx Associated precipitating cause/factor, if any
1. Dehydration Rx- Fluid resuscitation- Rate/amount depends on volume status + cardiac and renal status
a. Initial correction either by Isotonic NaCl solution or Ringer Lactate

b. Recommended schedule for restoring fluids is as follows:
1. Administer ≥ 2 L during the first hour. 4. Administer 1 L over next 4 hours, depending on the
2. Administer 1 L during the second hour. degree of dehydration
3. Administer 1 L during the following 2 hours 5. Thereafter depending on clinical situation
c. When euvolemic, switch to half Normal NaCl, particularly if hypernatremic
d. When blood sugar is ≤ 200-180 mg/dl, Isotonic NaCl is replaced with 5-10% D to prevent any hypoglycaemia
induced by Insulin infusion
2. K- imbalance- KCL infusion should be started from the beginning as Insulin will start to shift K rapidly
into cells causing Extracellular Hypokalemia- KCl is added to the infusion fluid
If K is greater than 6 mEq/L- no K supplement If K is 3-4.5 mEq/L- KCl 20 mEq/h
If K is 4.5-6 mEq/L- KCl 10 mEq/h
Monitor Potassium level regularly
3. Abnormal Glucose- Insulin Infusion- Monitor blood glucose hourly at bedside till it’s stabilized
Initially Continuous IV Short acting Insulin infusion using an infusion pump
4. Antibiotic- Empiric antibiotics on suspicion of infection
5. Anticoagulation- Prophylactic Heparin- Severe dehydration can cause hyperviscocity precipitating DVT
6. After the patient is stable, further/a long term management plan of DM should be drawn up- adjust Insulin and/ or
OHAs on the basis of glucose level.
SGLT 2 inhibitor
Sodium-dependent glucose cotransporters/ sodium-glucose linked transporter (SGLT) are a family of glucose
transporter found in the Small intestinal mucosa (SGLT1) and the Proximal tubule of the nephron. They contribute
to renal glucose reabsorption.
Mechanism of glycaemic control
These drugs by inhibiting subtype 2 sodium-glucose transport protein (SGLT2), which is responsible for at least 90% of
the renal glucose reabsorption lowers blood glucose level. Additionally water is eliminated by osmotic diuresis,
resulting in a lowering of blood pressure.
Indication
As an adjunct to diet and exercise to improve glycaemic control in adults with T2 DM, not recommended in patients
with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
Drugs Canagliflozin; Dapagliflozin;Empagliflozin
S/E
Hypotension
Ketoacidosis
Impairment in Renal Function
Hyperkalemia
Hypoglycemia (with concomitant use with Insulin and Insulin secretagogues
Incretin
Incretins are a group of GI hormones that decrease blood glucose levels.
Functions:
1. Stimulates increase amount of insulin released during postprandial state
2. Slow the rate of absorption of nutrients into the blood stream by reducing gastric emptying
3. Inhibit Glucagon release from the alpha cells of the islets of Langerhans
Physiology
The two main incretin like molecules are
1. Glucagon-like peptide-1 (GLP-1)
2. Gastric inhibitory peptide: also called Glucose-dependent insulinotropic polypeptide or GIP
Both GLP-1 and GIP are inactivated by Dipeptidyl peptidase-4 (DPP-4)
GLP 1 agonist
2 groups OHAs exert hypoglycaemic effects by affecting Incretins

1. DPPP4 inhibitors- Gliptins-Vilda/Saxa/Lina/Sita
2. Incretin mimics- GLP-1 analogues- Exenatide; Liraglutide
Next few topics are for the “Short notes” lovers!!.......
Primary Hyperaldosteronism/ Conn's syndrome…(“Ordinary lovers!!”)
Overproduction of Aldosterone
Types:
Primary/ Conn's syndrome: Excess production of Aldosterone from the adrenal glands due to “Intrinsic” disease of
the adrenal: hyperplasia or tumors: Aldostreone secreting adrenal adenoma
Secondary: CCF/CLD/Nephrotic syndrome/ CKD (these lead to overactivation of RAAS…“high renin” state leading to
Overproduction of Aldosterone
Clinical features: Resistant hypertension with recurrent Hypokalemia
Suspect if:
Those who have sustained blood pressure above 150/100 in three separate measurements taken on different days;
People who have hypertension resistant to three conventional antihypertensive drugs;
People whose hypertension is controlled with four or more medications;
People with hypertension and low levels of Potassium in the blood;
Those who have hypertension and a mass on the adrenal gland called an adrenal incidentaloma;
Young people with hypertension and a family history of early-onset hypertension (before age 30)
All hypertensive first-degree relatives of patients with primary Aldosteronism
Investigations:
Blood:
1. Electrolyte: Na, K: typically Recurrent Hypokalemia
2. Aldosterone Renin ration (ARR) (Low plasma renin plus High plasma aldosterone concentration)
ARR value in an individual that is higher than the cutoff indicates primary hyperaldosteronism
3. Imaging: CT Adrenals
4. Adrenal venous sampling (AVS) to make the distinction between unilateral and bilateral adrenal disease
Treatment
Surgical: Laparoscopic adrenalectomy for patients with unilateral PA (ie, aldosterone-producing adenoma [APA] or
unilateral adrenal hyperplasia
Medical: If a patient is unable or unwilling to undergo surgery or bilateral disease: medical treatment with
Mineralocorticoid receptor antagonist: Spironolactone/ Eplerenone
Dwarfism…( “ Extra-Ordinary lovers!!”)

Dwarfism generally defined as an adult height of 4 feet 10 inches or less.
2 broad categories:
Disproportionate dwarfism- If body size is disproportionate- very short trunk and shortened (but disproportionately
large) limbs with head disproportionately large compared with the body. Examples are
Achondroplasia
Spondyloepiphyseal dysplasias
Diastrophic dysplasia
Almost all people with disproportionate dwarfism have normal intellectual capacities
Proportionate dwarfism A body is proportionately small if all parts of the body are small to the same degree and
appear to be proportioned like a body of average stature. So the head, trunk and limbs are all small, but they're
proportionate to each other. Examples are
Growth hormone deficiency
Turner syndrome
Investigation- Hormone study/skeletal xrays/Genetic tests
Treatment- GH in appropriate cases Social/Occupational rehabilitation
Metabolic syndrome......(“obsessive lovers!!)
Metabolic syndrome is a multiplex risk factor that arises from insulin resistance accompanying abnormal adipose
deposition and function.
It is a risk factor for Coronary artery disease, Diabetes, NASH.
C/F- ≥ 1 of the following
Hypertension
Hyperglycemia-DM and its complications
Hypertriglyceridemia- Xanthomas or Xanthelasmas
Abdominal obesity
Chest pains or shortness of breath: Suggesting the rise of cardiovascular and other complications
Acanthosis nigricans- In patients with insulin resistance
Metabolic syndrome is diagnosed when a patient has at least 3 of the following 5 conditions:
FBG ≥100 mg/dL (or receiving drug therapy for hyperglycemia)
BP ≥130/85 mm Hg (or receiving drug therapy for hypertension)
TG ≥150 mg/dL (or receiving drug therapy for hypertriglyceridemia)
HDL< 40 mg/dL in men or < 50 mg/dL in women (or receiving drug therapy for reduced HDL-C)
Waist circumference ≥ 40” men or 35” in women
Treatment
1. Lifestyle modification- lose weight/Healthy diet +/- dietary modification
2. Medications
Antihypertensive Antidiabetic- Preferred agent is an Insulin-sensitizing
Antilipidemic- Statin/Fibrate agent - Metformin
Achondroplasia… (“Orgasmic” lovers!!!)

Achondroplasia is one of the most common cause of disproportionately short stature. This disorder usually results in
the following:
 An average-size trunk
 Short arms and legs, with particularly short upper part of the arms and that of legs
 Limbs are short but disproportionately large compared with the body
 Short fingers, often with a wide separation between the middle and ring fingers
 Limited mobility at the elbows
 A disproportionately large head, with a prominent forehead and a flattened bridge of the nose
 Progressive development of bowed legs
 Progressive development of swayed lower back
 An adult height around 4 feet
Kideny-CTD-Electro
Chronic kidney disease (CKD)
CKD= “abnormalities of kidney function or certain type of structural abnormality present persistently for > 3
consecutive months.”
Definition of CKD includes all individuals with markers of kidney damage (see below*) or those with an estimated
GFR (eGFR) of less than 60 ml/min/1.73m2 on at least 2 occasions 90 days apart (with or without markers of kidney
damage).
Presence of any of the following for at least 3 months:
1. Evidence of kidney damage with/ without reduced GFR
OR
2. GFR ≤60 ml/min/1.73 sq.mt body surface area with/ without Evidence of kidney damage
Markers of kidney damage:
1. Biochemical abnormalities: Urea↑ Creatinine↑ 3. Radiological evidence of structural abnormalities
2. Urinary abnormalities: 4. Histopathological abnormalities
 Albuminuria
 Cast Creatinine clearance (CrCl): Putting it simply “it
 haematuria (presumed or confirmed of Renal origin) determines whether the kidneys are functioning
normally”- Specifically, it gauges the rate at which
Stages of CKD: Creatinine (representative of renally cleared waste
Stage GFR (Normal: ≥90) products) is "cleared" from the blood by the kidneys.
1 Evidence of kidney damage +ve but GFR ≥90 Calculation of CrCl is quite complicated and therefore
2 60-89 is NOT A VERY PRACTICAL option.
So, a surrogate marker of CrCl has been in use for
3 30-59
many years……which is GFR.
4 15-29
Creatinine clearance (CrCl) is APPORXIMATELY an
5 <15 estimate of Glomerular Filtration Rate ( GFR )…so
“Health of the Kidneys” are assessed by Estimating the
eGFR
person’s GFR (e-GFR)
[140- age] × Weight (Kgs)/ 72 × Creatinine (mg/dl)
(female: Multiply above by 0.85)
Causes of CKD:
Causes Non Diabetic Non hypertensive causes
Glomerular diseases Glomerulonephropathy
Tubulo-interstitial diseases Autoimmune diseases
1. Diabetes Drugs
2. Hypertension Vascular diseases Fibromuscular dysplasia
Cholesterol emboli
Cystic and congenital diseases Alport syndrome,Polycystic kidney disease
Medullary cystic disease
ESRD: It is that stage of kidney disease where without renal replacement therapy (dialysis/ renal transplantation),
patient will not survive.
Azotemia: Accumulation of nitrogenous substance in the blood due to reduced renal clearance.
Uremia: Clinical manifestations due to azotemic condition.
Pathophysiological effects of CKD with mechanism of clinical manifestations in CKD:
≥1 of the following abnormalities MAY occur in VARYING COMBINATION
A-Azotemia: (accumulation of toxic N2 substances due to reduced renal clearance)-
 Constitutional symptoms
 Encephalopathy
 Pericarditis
 Peripheral neuropathy
B- BP: tendency to get increased. (Hypertension is a cause as well as a complication of kidney disease)
Accelerated atherosclerosis
Na+/ water retention
Biochemical disturbance: ≥1 of the following abnormalities MAY occur
 Na: low: due to dilutional hyponatremia secondary to fluid retention
 K: high: due to decreased renal clearance
 H+: high: due to decreased renal clearance of metabolically produced acids
 HCO3: low due to metabolic acidosis
 PO4: high due to decreased renal clearance
 Ca: low due to decreased Vitamin D
 Vitamin D: decreased due to impaired synthesis of active metabolite 1, 25 dihydroxycholecalciferol
 Urate: high due to decreased renal clearance of Urate
Bone-Effects on bone metabolism/Renal osteodystrophy( details: see below))
Blood- Anaemia: Erythropoietin (EPO) synthesis: most important cause
Marrow suppression by azotemic toxins
↓RBC life span
C-Coagulation: due to platelet and coagulation factor dysfunction (Just to keep a “C”!!..so not at all imp)
D-Decreased urine output (some patients have “ good” urine output inspite of significant damage of Kidney)
E-Etiology related manifestations
F-Fluid overloading: due to decreased renal elimination of fluid
a. Systemic venous congestion…….resembles RHF b. Pulmonary congestion…………...Resembles LHF
Renal osteodystrophy:
Effects of CKD on bone metabolism
CKD
↓PO4- clearance ↓1,25 (OH)2 cholecalciferol
↑Serum PO4- level ↓Calcium absorption

(PO4 binds free Ca)
↓Serum Ca++ (Hypocalcemia)
↑PTH secretion
Secondary hyperparathyroidism
Bone demineralisation
Clinical features: Asymptomatic OR : ≥1 of the followings in VARYING COMBINATION
A: Azotemia:
1. Constitutional symptoms:
 Anorexia  Metallic taste in mouth
 Nausea  Wasting of the muscles
 Refractory hiccup
2. CNS (symptoms of uremic encephalopathy):
 Altered sensorium  Delirium
 Behavioral disturbances  Flapping tremor
 Confusion/Convulsion/Coma  ↓GCS
3. Pericarditis: Pericarditic chest pain +/- Pericardial rub
B: BP: tendency to get increased BP
B: Biochemistry: all biochemical disturbance can be ASYMPTOMATIC or symptomatic
 Low Na: Encephalopathy
 High K: Arrhythmia
 High H+: Acidotic breathing
 Low Ca: Hypocalcemic manifestations: Tetany
 Low Vitamin D: Bone pain/spontaneous fracture/ delayed union or nonunion/Proximal myopathy
 High Urate: Gout
MOST IMPORTANT thing to realize
B: Bone manifestations: ABCDEF...NO fixed order/NO chronology of their appearance
 Asymptoamtic
 Bone pain/spontaneous fracture/ delayed union or nonunion
Coagulopathy: Asymptomatic or Spontaneous bleeding
Decreased urine output: starts to fall only after CKD reaches its advanced stages
Etiology: Manifestations due to underlying disease
F: Fluid overload: Symptoms and signs are mainly due to volume overload (and may resemble heart failure)
Symptoms:
 Progressive swelling
 Pulmonary congestion: Shortness of breath, orthopnea, PND
Signs:
 Signs of systemic venous congestion: Edema, ↑JVP
 Signs of pulmonary congestion: a.Hypoxia: Low O2 sat/Tachypnoea b. Bilateral crepitations
Investigation
1. To look for different biochemical and systemic effects of CKD
2. To detect the underlying cause
1.Blood biochemistry:
 Urea creatinine: ↑  ABG: pH↓ (due to ↓HCO3-)
 Na+: Normal/ ↓ (due to dilutional hyponatremia)  Vitamin D level: Normal/ ↓
 K+: Normal/ ↑  PTH level: Normal/ ↑
Biochemistry: DOESN’T have to be
 Ca++: Normal/ ↓  Uric acid: Normal/ ↑
abnormal ALWAYS
 PO4-: Normal/ ↑  Hb level: Normal/ ↓
2.Urine: Routine examination: To look for abnormalities which give an idea about the type of underlying disease
 Albuminuria: 24 hour urinary Albumin or “Spot” urine sample for Albumin: Creatinine ratio (ACR)
 Any cast: particularly RBC case, tubular cast
3.(KUB) USG KUB(P): Bilateral small kidneys (seen in CKD)Unilateral small kidney (seen in renal artery stenosis).
4. Chest X-Ray: To look for any pulmonary congestion
5. ECG, Echo: To look for any cardiac pathology
6. Renal biopsy: In selected cases only: confirms the underlying type of kidney disease
7. Relevant investigation(s) to detect the cause
Treatment
General treatment
R:
1. Regular monitoring of urine output: 3. Regular monitoring of body weight
particularly in significant CKD 4. Regular monitoring of blood biochemistry
2. Regular monitoring of volume status
E: Treatment of the underlying etiology
N: Nutrition:
Dietary modification
 Fluid and salt restriction
 Dietary protein restriction As you are going thorough this clinical
scenario……“NEED” to remember “WHEN”
 Restriction of K+:
you have seen the word “DIALYSIS”!!!
 Parboiling of rice (to discard water after boiling)
 Avoid juicy food
 Avoid beverages: rich in phosphates
A:
1. Avoid all nephrotoxic drugs
2. Adjust the dose of drugs according to creatinine clearance
L: Look for common complications:
 Features of dehydrations (due to diuretics + fluid restriction) or hypervolemia
 Features of dyselectrolytemia
Specific treatment
F: Fluid balance:
 Dietary Fluid restriction Remember!!.....These patients MAY ALSO come with
 Diuretic: Furosemide/Metolazone dehydration- “Kidney related” cause like “overdiuresis” OR
 Dialysis “Not kidney related” (m)ANY causes: when they MUST be
A: Acidosis: rehydrated: Oral/ IV fluid cautiously.
 Mild to moderate: NaHCO3 if required PS: CKD is NOT ALWAYS fluid restriction!!
 Severe: Dialysis
A: Anemia:
 Packed cell transfusion if symptomatic or Hb less than 8 gm/dl
 Long term Recombinant Erythropoietin therapy
I: Infection: Treat with appropriately Renal adjusted dose of antibiotics.
L: Loss of blood due to associated coagulopathy: FFP
Ur: Uremic encephalopathy: dialysis Uremic pericarditis: dialysis
E: Treat any electrolyte imbalance
As you are going thorough this clinical scenario…….“NEED” to remember
↓Na+: Fluid restriction Diuretics
“WHEN” you have seen the word “DIALYSIS”!!!
↑K+:
 Avoid K+ rich diet
 Beta 2 agonist: Nebulized Salbutamol
 Binder: K+ binder: Sodium Polysterene Sulfonate
 Ca-gluconate IV Dextrose + Insulin OR Nebulized salbutamol
 Dextrose + Insulin IV
 Dialysis
↑ PO4-:
 PO4- restriction
 PO4- binding agents (almost like “Chelators”):
 Calcium agents: Ca-carbonate/ Ca-acetate
 Non-calcium agents: Sevelamer
↓Vit-D: Cholecalciferol/ Calcitriol
↓Ca: Ca-salts
↑PTH: Calcimimetics: Cinacalcet
↑ Urate: As you are going thorough this clinical scenario…….“NEED” to remember
1.Low Purine diet “WHEN” you have seen the word “DIALYSIS”!!!
2.Hypouricemic agents:
 Allopurinol
 Febuxostat
End stage renal disease: Renal Replacement therapy
a. Dialysis:
o Hemodialysis I’m sure by this time you know “WHEN” does a CKD patient “NEED” it!!!
o Peritoneal dialysis
b. Kidney transplantation
Dialysis
Type of Renal replacement therapy by which waste and excess water from the blood is removed in kidney failure.
Uses: 1. Acute kidney injury 2. Chronic kidney disease
Indications ‘’AE(I)OU’’!!
Acidosis- severe Metabolic acidosis
Electrolyte abnormality- severe hyperkalemia
Increased Creatinine: in itself is NOT an indication!!
Overload of fluid: refractory to conservative treatment i.e dietary fluid restriction & diuretics
Uremic complications- Constitutional manifestaitons/Encephalopathy/Pericarditis
Hemodialysis-
Patient's blood is pumped through the blood compartment of a dialyzer which is composed of many tiny
hollow synthetic fibres acting as semipermeable membrane. Blood flows through the fibres, dialysis solution
(Dialysate) flows around the outer surface of the fibres, and water and wastes move between these two solutions. The
cleansed blood is then returned via the circuit back to the body. Ultrafiltration occurs by increasing the hydrostatic
pressure across the dialyzer membrane. This usually is done by applying a negative pressure to the dialysate
compartment of the dialyzer.
Tried my best to write ‘types of dialysis’ in a “:NONMEDICAL” way !!.............
Peritoneal dialysis
In peritoneal dialysis, a sterile solution called dialysate is run through a tube into the peritoneal cavity, where the
peritoneal membrane acts as the semipermeable membrane. Diffusion and osmosis drive waste products and excess
fluid through the peritoneum into the dialysate until the dialysate approaches equilibrium with the body's fluids.
Then the dialysate is drained, discarded, and replaced with fresh dialysate.
Hemofiltration .............Sorry my dear “Non MBBS-DM Nephro”s!!
Hemofiltration is a similar to hemodialysis, but the principle is different. The blood is pumped through a dialyzer or
hemofilter as in hemodialysis, but no dialysate is used. A pressure gradient is applied; as a result, water moves across
the very permeable membrane rapidly, dragging along with it many dissolved substances, including ones with large
molecular weights.
Complications 1. Dialysis dysequilibrium syndrome 2. CAPD-associated peritonitis
CKD treatment Alternative format!!!
Problems Intervention
Azotemia Dietary protein restriction
Constitutional features Dialysis
Encephalopathy
Pericarditis
BP Antihypertensive
Blood Anaemia: Packed cell transfusion
Recombinant Erythropoeitin
Biochemical abnormalities Regular monitoring of blood biochemistry
Low Na: 1.Fluid restriction
2. Diuretic
3. Hypertonic (3%) Saline if severely symptomatic
High K  Avoid K+ rich diet
 Dialysis
High H+ (Acidosis) Mild to moderate: NaHCO3 if required Severe: Dialysis.
Low Ca: Ca-salts
Low Vitamin D: Cholecalciferol/ Calcitriol
High Urate: Low Purine diet
Hypouricemic agents: Allopurinol Febuxostat
High PTH: Calcimimetics: Cinacalcet
Coagulopathy FFP if bleeding maifestations
Decreased urine output Monitor urine output
Diuretic
Etiology Rx of the underlying disease
Fluid Overload Dietary Fluid restriction
Diuretic: Furosemide/Metolazone
Dialysis
Anemia in CKD
Pathogenesis/ mechanism:
1. Erythropoietin (EPO) synthesis 4. Coexistent iron deficiency
2. Marrow suppression by azotemic toxins 5. ↑Loss of folic acid- patients on dialysis)
3. ↓RBC life span 6. Blood loss due to coagulopathy.
Clinical features:
A. Asymptomatic
B. If symptomatic:
A. Anemic look(pallor) D. Dizziness
B. Breathlessness E. Exercise intolerance
C. Cardiac palpitation F. Fatigue
Investigation:
1. Full blood count:Hb: ↓Normochromic anemia.
2. Serum iron/ ferritin/ B12/ folic acid should be checked to rule out any coexisting deficiency.
Treatment:
Symptomatic treatment:
1. Packed cell transfusion
2. Correct IF any underlying iron deficiency: Usually IV iron supplementation is given
3. Long term s.c. Recombinant Human EPO (rhPO)injection- Epoetin alpha/BetaDarbo
4. Look for any other causes of anemia.
Acute kidney injury (AKI)
Definition:
Any 1 of the following:
1. Serum creatinine increases by ≥0.3 mg/dL in 48 hours
2. Serum creatinine increases by ≥1.5 times of baseline in last 7 days
3. Urine output ≤0.5 mg/kg/hr for 6 consecutive hours
Stages: Rarely used clinical practice!!! (CKD stages very frequently used)
Stage Increase in serum creatinine
1 1.5 times of baseline
2 1.5-2.9 times of baseline
3 ≥3 times of baseline
Oliguria:
 Urine output 100-500 ml in 24 hours
 Urine output ≤0.5 ml/kg/hr for at least 6 hours
Anuria: Urine output <100 ml in 24 hours.
Causes of AKI:
1. Pre-renal causes: Renal hypoperfusion leading to low GFR and AKI BUT not structural damage to the kidneys
 Hemorrhagic shock (massive bleeding)
 Hypovolemic shock (severe dehydration)
 Cardiogenic shock (MI, acute LVF, acute RVF)
 Fluid sequestration (septicemic shock, acute pancreatitis)
 Septicemic shock (abnormal peripheral vasodilatation)
 Severe burn (↑ Insensible loss).
2. Intrinsic renal causes: Structural damage to the kidneys

I. Acute glomerular diseases:
 RPGN
 MPGN
II. Acute tubular necrosis:
 Ischemic (pre-renal causes)
 Toxins (endogenous and exogenous).
III. Acute interstitial nephritis:
 Iatrogenic (β-lactam antibiotics)
 Idiopathic
 Infection (CMV)
3. Post-renal causes: An obstructive uropathy can cause AKI
 Calculous
 Carcinoma
 Bladder outlet obstruction
 Stricture
Acute tubular necrosis (ATN)
Acute tubular damage leading to acute malfunctioning of kidney.
Causes:
You keep on reading this box IF YOU are a baby…Long Q may be
1.Ischemic causes: Pre-renal causes
ATN: answer remains the same as AKI only “intro” part is different!!
2.Toxins
• Endogenous toxins
Hb: Massive Intravascular Hemolysis: Mismatched blood transfusion/Snake bite/Complicated Malaria
Myoglobin: Crush injury/ rhabdomyolysis
Urate crystals: Hyperuricemia
• Exogenous toxins Drugs: Aminoglycosides Dye: Radiocontrast dye
Clinical features: of ANY patient of AKI
A: Azotemia:
1.Constitutional symptoms:
 Anorexia  Refractory hiccup
 Nausea  Metallic taste in mouth
2.CNS (symptoms of uremic encephalopathy):
 Altered sensorium  Delirium
 Behavioral disturbances  Flapping tremor
 Confusion/Convulsion/Coma  ↓GCS
3.Pericarditis: Pericarditic chest pain +/- Pericardial rub
B: BP: Low if Hypovolemia is the cause of AKI
B: Biochemistry: all biochemical disturbance can be ASYMPTOMATIC or symptomatic
 Low Sodium: Encephalopathy
 High Potassium: Arrhythmia
 High H+: Acidotic breathing As kidneys start to regain its function recovery of tubular
 Low Ca: Hypocalcemic manifestations: Tetany function (salt and water retention) lags behind the recovery
D: Decreased urine output : Oliguric/ Anuric of glomerular function (filtration) and patients go into a
E: Etiology: Manifestations due to underlying disease polyuric phase temporarily.
F: Fluid STATUS
 Hypovolemia: IF Pre renal/Hypovolemic ATN
A. Altered sensorium
B. BP- low
C. C: ↑ Capillary refill time (≥2 sec)
D. Decreased urine output+ Dark coloured urine
Dry mucous membrane
Decresed skin turgor
E. Extremity: Cold clammyTachycaridaWeak pulse
F. Features of underlying causeH/O blood loss/ volume loss/ condition causing fluid sequestration
 Hypervolemic: AKI patients usually DON’T develop HYPERVOLEMIA unless OVERENTHUSIASTIC fluid
Replacement was done to treat initial HYPOVOLEMIA If Fluid “overload”:
Symptoms: Pulmonary congestion: Shortness of breath, orthopnea, PND
Signs: Signs of pulmonary congestion: a.Hypoxia: Low O2 sat/Tachypnoea b. Bilateral crepitations
Stages of progression of AKI:
Stage Description
Stage of progression Due to sudden assault on kidney, GFR abruptly decreases which in turn leads to ↓urinary output and
accumulation of excessive salt, water and toxins
Stage of maintenance Falling GFR reaches its lowest limit leading to a full blown picture of AKI
Stage of recovery With treatment, kidney starts to regain its function. Often in this stage, recovery of tubular function
(salt and water retention) lags behind recovery of glomerular function(filtration). Patient goes into
polyuric phase temporarily.
Investigations of AKI:
1. Full blood count
2. Urea creatinine: ↑
3. Electrolyte:
o Na+: Variable (depends upon the degree of fluid and solute loss)
o K+: Normal/ ↑ ( even hypokalemia may occur in diarrhea/ overdiuresis)
4. ABG: Metabolic acidosis
5. Urine routine examination/ microscopic examination:Often gives vital clue of underlying causes.
eg.:Tubular cast is suggestive of ATN RBC cast ± Dysmorphic RBCs is suggestive of GN.
6. KUB-USG: To look for any obstructive uropathy.
7. Chest X Ray:To look for any pulmonary edema.
8. ECG:To rule out any cardiac effects due to hyperkalemia.
9. Echocardiogram: IVC collapsibility/ fullness indicates “volume status”
10. Investigation(s) to assess the underlying disease.If cause is not obvious, patients are often investigated for:
 Underlying glomerulonephritis: Autoantibody markers
 Endogenous toxins: Serum uric acid, Serum + urinary protein electrophoresis
 Renal biopsy.
Treatment
General treatment:
R: Regular monitoring of volume status:
a. Urine output [intake-output chart]
b. Central venous pressure measurement
c. Echocardiogram: Status of IVC.
E:Treatment of the etiology
N:Nutrition: Protein and K+ restriction.
A:Avoid all nephrotoxic drugs/Adjust dosage of dugs according to creatinine clearance
L:Look for complications:
 Hypo/hyper-volemia
 Dyselectrolytemia
Specific treatment:
F:Fluid balance: Treatment of fluid imbalance:
Hypovolemia
 IV fluid resuscitation
 If required: Packed cell transfusion
 Vasopressor: Noradrenaline/ Adrenaline
 Forced diuresis: If urine output does not improve in spite of adequate fluid resuscitation; desperate
attempt can be tried by giving IV Furosemide high dose + Osmotic diuretics (Mannitol).
Hypervolemia: 1.Salt and water restriction 2.Loop diuretics:IV: Furosemide
A:Treatment of acidosis:Mild to moderate: IV NaHCO3Severe: Emergency dialysis.
I:Infection:Treat with antibiotics.
Ur: Uremic complications (if present): Emegency Dialysis
E: electrolyte imbalance: E: “End stage “AKI: Dialysis
 Na+ imbalance: Treatment depends upon the underlying cause
Indications of dialysis:
 Hyperkalemia:
Uremic encephalopathy
 Avoid K+ rich diet
Refractory volume overload
Significant acidosis
Severe hyperkalemia
 Dialysis
Nephrotic syndrome
It is a condition characterized by 1. Heavy proteinuria (>3 gm/24 hr) 2. Hypoalbuminemia 3. Hyperlipidemia
Causes: Filtration barrier damage due to
Podocytopathies Immune complex deposit Other substance deposits

1. Minimal change disease 1. Membranous 1. Diabetes
2. FSGS ● Primary 2. Amyloidosis
● Primary ● Secondary
● Secondary ▪ Drugs
Drugs ▪ Infection
Infection ▪ Malignancy
Malignancy ▪ Connective tissue disease
2. Membranoproliferative
▪ Infection
▪ Connective tissue disease
Pathophysiological effects: 5H
1. Hypoalbuminemia: Due to increased permeability Glomerular basement membrane causing heavy proteinuria
2. Hyperlipidemia: Due to
I. Accelerated lipid synthesis
II. Loss of lipid metabolizing protein
3. Hypercoagulability: Due to loss of circulating anticoagulant Antithrombin 3.
4. Hypervolemia:
Hypoalbunimemia-- > Colloidal osmotic pressure ↓ ---> Fluid leakage --->Intravascular volume depletion--->
Renal hypoperfusion↑ --->Activity of RAS system---> Secondary hyperaldosteronism---> Na+ and water
retention---> Hypervolemia
5. Hypo-gamma-globulinemia: patient prone to infection.
Clinical features:
Symptoms:
 Progressive swelling of body
 Recurrent infection particularly in children
 Patient may develop unprovoked DVT
particularly renal vascular thrombosis, causing acute loin pain ± hematuria.
Signs:
 Edema: ++
Puffy/ swollen face with Periorbital edema
 Ascites: ++
 Scrotal swelling
 Signs of pleural effusion: Bilaterally
Signs and symptoms of underlying disease may be present.
Investigation:
1. Blood:
 Full blood count
 Urea-creatinine: Derangement in renal function is often absent
 Na+: Normal/ ↓ (due to dilutional hyponatremia)
 Liver function test:
o Albumin: ↓ (due to “glomerular loss”)
o Globulin: ↓ (due to “glomerular loss”)
o Liver enzymes: Normal
 Fasting lipid profile: May be deranged as a long term complication
2. Urine (routine and microscopic examination):
 Protein: ++
 24 hour urinary albumin: >3 gm
3. ECG and Echocardiogram: To assess cardiac function
4. Investigations to diagnose underlying type/cause of Nephrotic syndrome:
 Anti-phospholipase A2 receptor (PLA2R) antibodies are highly specific of primary membranous nephropathy.
 In Primary glomerular diseases: often renal biopsy confirms the diagnosis.
Treatment:
Supportive treatment: Management of complications
1. Hypervolemia: a. Dietary salt and fluid restriction b. Diuretics: Loop diuretics
2. Hypoalbuminemia: High protein diet. No role of Albumin infusion as it will get lost as well
3. Hypertension: current recommendations- ≤ 130/80 mm Hg should be the treatment goal. ACE-I/ARB 1st-choice
4. Hypercoagubality: A “selective” or individualized rather than a “routine” approach to prophylactic
anticoagulation seems justified in Nephrotic syndrome
5. Hyperlipidemia: Statin
6. Hypoglobulinemia: A high order of clinical vigilance for bacterial infection is vital in nephrotic patients
particularly in patients with ascites, in whom the fluid should be examined microscopically and cultured for SBP
Vaccination: Pneumococcal vaccine recommended
Definitive treatment: Depends upon the cause/type of Glomerular disease. However, in many glomerular diseases,
the following drugs may be prescribed:
 Corticosteroid: Often patient needs long term steroid treatment
 Steroid sparing agents:
 Mycophenolate mofetil  Cyclosporine
 Levamisole  Cyclophosphamide
 Tacrolimus  Rituximab
Next segment
Nephrotic treatment: Alternative “format”

Answer was specifically (on demand of 1 of your senior batch) prepared for Paediatrics …However this can be “used”
for adults as well……
First Episode of Nephrotic Syndrome: Absence of hypertension/hematuria/azotemia
Prednisolone 2 mg/kg daily for 6 weeks, followed by 1.5 mg/kg on alternate days for 6 weeks
If present
Infrequent relapses Frequent relapses/ Steroid dependence Steroid resistance
Prednisolone 2 mg/kg daily 1. Alternate day prednisolone to Therapy based on renal biopsy findings
until remission, then 1.5 mg/kg maintain remission
on alternate days for 4 weeks 2. Assess steroid threshold
Threshold: < 0.5-0.7 mg/kg on alternate days > 0.5-0.7 mg/kg on alternate days or steroid toxicity
Alternate day Prednisolone for 9-18 months Levamisole

Cyclophosphamide
To make it an “adult” answer!!!.....replace the “_______” part with
Tacrolimus
the phrase “appropriate/ certain dose”….can try it for Paeds as well!!
Mycophenolate mofetil
Cyclosporin
Admit if significant edema/ severe infection/azotemia
Body weight monitoring: gives an idea about volume retention/overloading
Complications: Look for any complications and treat accordingly
Diet:
Adequate in protein (1.5-2 g/kg) and calories: If persistent proteinuria: 2-2.5 g/kg of protein daily
Salt restriction: not necessary in most steroid sensitive pts, reduction of salt intake (1-2 g per day) is advised for those
with persistent edema/hypertension
Drugs:
 Antihypertensive: ACE inhibitors/CCB
 Ca++: Long-term calcium supplementation: if receives >3 months prednisolone (bone protection)
 Hypolipidemics: Statin. Steroid sensitive cases do not require it since lipids normalize following remission.
 Immunization:
1. Should complete ALL primary immunization.
2. Additional vaccines: Pneumococcal vaccine & Varicella vaccine
Edema: Since treatment with corticosteroids usually leads to diuresis within 5-10 days, diuretics are avoided unless
edema is significant. Diuretics should also not be given to patients with hypovolemia.
Examine for hypovolemia Yes volume replacement
No
Frusemide 1-3 mg/kg/day +/- Spironolactone 2-4 mg/kg/day
No response (no weight loss or diuresis in 48 h)
Double dose of frusemide until diuresis or maximum daily dose of frusemide (4-6 mg/kg/day) is reached
No response
“Intelligent” option…….
Add Hydrochlorthiazide 1-2 mg/kg/day or Metolazone 0.1-0.3 mg/kg/day Just the names of the diuretic!!
No response be it for Paed/Adults
Frusemide IV bolus 1-3 mg/kg/dose or infusion 0.1-1 mg/kg/h
No response
20% Albumin 1 g/kg IV followed by IV frusemide
Education: following are emphasized:
(a) Urine examination for protein at home using dipstick- should be done every morning during a relapse, during
intercurrent infections or if there is even mild periorbital puffiness. Fequency is reduced 1-2/week during remission.
(b) Maintain a diary showing results of urine protein examination, medications and any intercurrent infections.
(c) Ensure normal activity and school attendance
(d) Should receive appropriate immunization and other measures for protection
Complications of Nephrotic syndrome:
Disease related: Treatment related:
Hypertension Corticosteroid side effects: Cushing syndrome
Hypervolemia: Anasarca Hypovolemia: often due to overenthusiastic use of diuretic
Hyperlipidemia Immunosuppressive drug toxicity
Hypercoagubality: at risk for venous and rarely arterial thrombosis
Hypogammaglobulinemia: Infection: Viral and bacterial infections may precipitate relapses in patients previously in
remission.
1. Bacterial: particularly bacterial infection of the Ascitic fluid= SBP
2. Viral
3. Fungal infection
Organ damage: Renal failure
Nephrotic related definitions
Indications for kidney biopsy

At Onset
 Age of onset <1 year. • Renal failure not attributable to hypovolemia
• Gross hematuria, persistent microscopic hematuria or • Suspected secondary causes of nephrotic syndrome
• Sustained hypertension
After Initial Treatment
• Proteinuria persisting despite 4-weeks of daily corticosteroid therapy• Before considering Steroid sparing agent
Indications for referral to a pediatric nephrologist
1. Onset below 1-year of age
2. Family history of nephrotic syndrome.
3. Nephrotic syndrome with HTn, gross/persistent microscopic hematuria, impaired renal function, or extrarenal
features (e.g., arthritis, serositis, rash).
4. Resistance to steroid therapy.
5. Frequently relapsing or steroid dependent nephrotic syndrome.
Glomerulonephritis
Inflammation of the glomerulus which may affect podocytes/ glomerular basement membrane/ endothelium.
Types:Nephritic pattern (Hematuria + Hypertension)
Primary Secondary
Post infectious GN SLE (Lupus nephritis)
IgA nephropathy Vasculitis (Small and medium vessel disease)
Henoch Schonlein purpura ● ANCA (+)ve
Wegener's granulomatosis
Microscopic polyangitis
Churg–Strauss syndrome
● ANCA (-) ve
Goodpasture syndrome
Clinical features: Aymptomatic OR ≥ 1 of the followings
1. Hematuria (may be microscopic)
2. Progressively increasing BP
3. Constitutional symptoms: Fever, malaise, weakness. Weight loss
4. Often anemia is seen
5. AKI/ CKD can occur in some of the underlying types of GN.
Look for the following symptoms and signs: In all patients of suspected GN, particularly those coming with nephritic
pattern, an underlying connective tissue disorder/ vasculitis must to be looked for.
1. CNS manifestations: Headache/ focal neurodeficit (suggestive of vasculitis)
2. Eye symptoms: Red/ gritty/ painful eyes (suggestive of connective tissue disorders*)
3. ENT manifestations: Wegener’s granulomatosis
4. Lungs:
 Look for pleurisy/ pneumonitis/ acute shortness of breath (suggestive of Goodpasture syndrome);
 H/O asthma (suggestive of Churg–Strauss syndrome)
5. Intestinal symptoms: GI bleed, Post-prandial pain (suggestive of ischemia)
6. Vasculitic rash (suggestive of vasculitis)
7. Arthralgic manifestations (suggestive of rheumatoid arthritis).
Investigations:
A. Blood:
1. Full blood count:
 Hb: ↓ (due to hematuria/ chronic inflammation)
 WBC: ↑ (due to chronic inflammation)
 Platelet: Normal
 ESR/ CRP: ↑ (due to chronic inflammation).
2. Renal function: Urea creatinine Na+ K+ (to rule out renal derangement)
3. Serum albumin: Normal/Low (NOT as loa as in nephrotic spectrum of diseases)
4. Autoimmune markers:
 ANCA: +Ve in:
i. Wegener’s granulomatosis
ii. Microscopic polyangitis
iii. Churg-Strauss syndrome.
 Anti-GBM-antibody: +Ve in: Goodpasture syndrome
 Antinuclear antibody (ANA): +Ve in: SLE; to confirm: Anti-ds-DNA
 ASO titre: ↑ in PSGN.
5. Viral serology:
 Anti-HCV
 Anti-HIV
B. Urine (routine and microscopic examination):
1. RBC: +Ve
2. RBC cast
3. Dysmorphic RBC
4. Proteinuria: “Sub-nephrotic” range
C. 24 hour urinary albumin estimation
D. USG kidney: To assess kidney architecture
E. ECG and Echocardiogram: To assess cardiac function
F. Special tests:
Nature of which depends upon preliminary diagnosis.
If the cause of GN is obscure, patient often undergo renal biopsy to find out the exact type of disease.
Treatment:
A. Supportive treatment:
 BP control: Antihypertensives
 If edema present: Diuretics.
B. Definitive treatment: Depends on exact type of underlying disease.
 Corticosteroid +/- Immunosuppressive drugs: Mycophenolate mofetil/Rituximab/Azathioprine
C. Appropriate treatment of AKI/ CKD (if develops).
Post-infectious GN
Glomerulonephritis triggered by an infectious agent.
Causes:
1. β-hemolytic streptococcal infection (LRTI)
2. Staph.aureus (Infective endocarditis/ Lung abscess)
Clinical features:
 Preceding/ ongoing features of bacterial infection often present
 In case of PSGN, there is often a recent H/O severe LRTI: sore throat, cough etc.
 GN typically starts with hematuria along with progressive hypertension. In PSGN, there is almost always an
asymptomatic period between LRTI and onset of hematuria.
 Kidney dysfunction- rare.
Investigation:
1. CBC, CRP 5. Urine: Routine and microscopic examination
2. Urea, Creatinine, Na+, K+ 6. USG KUB
3. Blood C/S 7. Renal biopsy
4. ASO titre: often high
Treatment:
1. Salt restriction
2. Control of hypertension
3. Antibiotic to clear any residual infection (although its role is doubtful).
IgA nephropathy/ Berger’s disease
Immune complex mediated GN which commonly occurs in children.
Clinical features:
 Recent history of LRTI: Fever, sore throat, cough often present
 GN: Mostly present with hematuria and progressive hypertension. Usually, no latent period between LRTI and
onset of hematuria is present.
 Renal dysfunction: not common
Investigation:
1. CBC, CRP 5. Urine: Routine and microscopic examination
2. Urea, Creatinine, Na+, K+ 6. USG KUB
3. Blood C/S 7. Renal biopsy
4. ASO titre: Not high
Treatment: Supportive: Control of hypertension.
Henoch-Schonlein Purpura (HSP)
It is a type of small vasculitis affecting children.
Clinical features:
 H/O preceding episode(s) of URTI/LRTI
 Hematuria due to GN
 Skeletal change: Arthralgia
 Small bowel ischemia: Leading to abdominal pain and melena
 Purpura: Typically palpable purpuric spots over the buttocks and posterior compartment of lower limb;
Investigation:
1. CBC, CRP 6. USG KUB
2. Urea, Creatinine, Na+, K+ 7. Renal biopsy: deposition of IgA and C3
3. Blood C/S 8. Skin lesion shows: Leukocytoclastic vasculitis.
4. ASO titre: Not high
5. Urine: Routine and microscopic examination
Treatment: Henoch-Schonlein Purpura (HSP)
 Supportive:  Definitive: In severe cases; Rituximab/ Plasma
I. Salt restriction exchange
II. Control of hypertension
Minimal change disease (MCD)
Commonest nephrotic pattern glomerulopathy in children; rarely may occur in adults.
Clinical features:
Typically presents with features of nephrotic syndrome:
 Progressive swelling
 Edema: +Ve
 Ascites: +Ve
 Signs of bilateral pleural effusion: +Ve
 Hypertension may occur
Investigations:
Blood: K+: Normal
CBC +CRP Serum albumin: Typically ↓
Urea +Creatinine: Mostly normal Urine (R/E and M/E): 24 hour urinary protein >3 gm
Na+: ↓ may be (dilutional hyponatremia)
Biopsy: Shows loss of foot processes (effacement) of podocytes. Rarely required, as mostly the disease is presumed.
Indications of renal biopsy:
I. Steroid resistant cases (proteinuria doesn’t significantly decreases even after 4 weeks of corticosteroid)
II. Steroid dependent cases.
Treatment:
A. Supportive: B. Definitive:
 Salt and fluid restriction  Corticosteroids
 Diuretics  Steroid sparing agents
 Control of hypertension (ACE-I/ ARB)
Membranous nephropathy
Commonest nephropathy in adults.
Causes:
1. Mostly idiopathic: Immune complex deposition occurs in glomerular capillary wall
2. Secondary causes:
I. Malignancy (Lung CA)
II. Infection (Hep B, Syphilis)
III. Drug induced
IV. Connective tissue disease
Investigation:
1. CBC 5. Serum albumin: Typically ↓
2. Urea +Creatinine: Mostly normal 6. Urine (R/E and M/E): 24 hour urinary protein >3 gm
3. Na+: ↓ may be (dilutional hyponatremia) 7. Renal biopsy: Shows deposition of IgG + C3.
4. K+: Normal
Treatment:
 Salt and fluid restriction  Corticosteroids
 Diuretics  Steroid sparing agents
 Control of hypertension (ACE-I/ ARB)
Urinary tract infection (UTI)

Infection anywhere in the urinary passage.
Site of infection: 1. Kidney: Pyelonephritis 2.Urinary bladder: Cystitis 3.Urethra: Urethritis.
Organisms: E.coli/Klebsiella/Proteus/Enterococci/Pseudomonas
Clinical features:
Constitutional:
Anorexia Focal (Urinary) symptoms:
Body weakness (Malaise) Urethritis: Dysuria/Burning during micturition
Chill (+rigor) Cystitis: Suprapubic pain (cystitis)
Confusion Pyelonephritis: Acute loin pain
Drowsiness Urinary incontinence (in elderly)
Emesis- in Pyelonephritis Mild hematuria
Fever
Investigation:
1. Blood: WBC count: ↑ (predominantly neutrophils) ESR/ CRP: ↑; Procalcitonin: ↑ may be
2. Blood culture: may be positive
2. Urinalysis (R/E and M/E):
 Pus cells(Neutrophils): +Ve (significant pyuria=  leukocyte esterase- +ve
when cell count > 7-10/ HPF)  Nitrite +ve- if nitrite forming orgm
 Protein: often +Ve  Microorganism may be seen
 RBC: often +Ve
3. Urine culture and sensitivity: Significant bacteriuria is said to be present when no. of CFU > /ml.
4. Imaging studies: USG-KUB (P)
Females with recurrent episodes of UTI/ males after 1st episode of UTI should ideally be investigated for any
underlying structural/ functional abnormality of urinary passage and should have an USG-KUB (P).
Treatment:
1. Antibiotics: Initially Empirical which can be modified according to urine C/S report, if required
Empirical Rx: Choice of drug- Depends upon: 1.Severity of infection 2. Previous urine C/S pattern (if any).
Any of the following drugs:
1. FQs: Ciprofloxacin/ Levofloxacin/ Ofloxacin 2. Cotrimoxazole 3. Nitrofurantoin.
2. In severe cases- 1. (Piperacillin/Tazobactum) 2. Carbapenem- Ertapenem/ Meropenem/ Imipenem
ESBL (Extended spectrum β-lactamase) producing organisms: These organisms are usually resistant to traditional β-
lactams (+ FQs) and sensitive to Carbapenem. Carbapenemase producing organisms: These organisms are sensitive to
Aztreonam/ Colistimethate.
Duration of treatment: Usually 5-7 days, however, in pyelonephritis, at least 14- 21 days.
2. Symptomatic Rx- Urinary tract Antispasmodic (Flavoxate) & Analgesic- (Phenazopyridine)
3. Preventive measures:
a. Personal hygiene b. plenty of fluid c. Correct structural defect: Urethral stricture/BNO/Vesico-ureteral reflux
Pyelonephritis
Pyelonephritis results from bacterial invasion of the renal parenchyma that often leads to renal scarring
Port of entry 1. Ascending from the lower urinary tract. 2. via the bloodstream
Types- Acute and Chronic
C/F
Constitutional:
Anorexia + nausea
Body weakness (Malaise)
Chill (+rigor)
Confusion
Drowsiness
Emesis- in Pyelonephritis particularly
Fever
Focal- Costovertebral angle pain + flank or costovertebral angle tenderness - Pain may be mild, moderate, or severe;
Investigation:
1. Blood: WBC count: ↑ (predominantly neutrophils) ESR/ CRP: ↑; Blood C/S- may be +ve
2. Urine analysis (R/E and M/E):
 Pus cells(Neutrophils): +Ve (significant pyuria= when cell count > 7-10/ HPF)
 Protein: often +Ve
 RBC: often +Ve
 Microorganism may be seen
 Dipstick leukocyte esterase test (LET) - Helps to screen for pyuria
 Nitrite production test (NPT) - To screen for bacteriuria
3. Urine culture and sensitivity: Significant bacteriuria is said to be present when no. of CFU > /ml.
4. Imaging studies: USG/ CT KUB
Treatment:
Antibiotics: Initially Empirical which can be modified according to urine C/S report, if required
Empirical Rx: Choice of drug- Depends upon: 1.Severity of infection 2. Previous urine C/S pattern (if any).
Any of the following drugs:
1. FQs: Ciprofloxacin/ Levofloxacin/ Ofloxacin 2.Cotrimoxazole 3.Nitrofurantoin.
2. In severe cases- 1. (Piperacillin/Tazobactum) 2. Carbapenem- Ertapenem/ Meropenem/ Imipenem
ESBL (Extended spectrum β-lactamase) producing organisms: These organisms are usually resistant to traditional β-
lactams (+ fluoroquinolones) and sensitive to Carbapenems. Carbapenemase producing organisms: These organisms
are sensitive to Aztreonam.
Duration of treatment: Atleast 14 days in selected/complicated cases upto 21 days.
Predisposing Factors for Recurrent Urinary Tract Infection

Immunosuppression Nosocomial factors and instrumentation Urinary tract anatomic abnormality
Chronic renal insufficiency Antibiotic-resistant bacteria Urethral valves
Diabetes mellitus Indwelling urinary catheter Vesicoureteral reflux
Immunosuppressant medications Intermittent catheterisation Bladder outlet obstruction
Renal transplant Nephrostomy tube Ureteral or urethral stricture
Ureteral stent Urolithiasis
Cystocele
ESBL
Bacteria that produce enzymes called extended-spectrum beta-lactamases (ESBLs) are resistant to many penicillin and
cephalosporin and often to other types of antibiotic. ESBL enzymes are able to hydrolyze most of the beta-lactam
antibiotics, including third-generation cephalosporins. In addition, ESBL-EC can also have co-resistance to SMX/TMP,
fluoroquinolones, and aminoglycosides
The 2 main bacteria that produce ESBLs are Escherichia coli (E. coli) and Klebsiella species.
ESBLs are derived from genes for the narrow spectrum betalactamases (TEM-1, TEM-2, or SHV-1) by mutations that alter
the amino acid configuration around the active site of these β-lactamases.
Rx
1. Carbapenem- Ertapenem/Imipenem/Meropenem
2. Nitofurantoin
3. Fosfomycin
For All you “Short notes Lovers”!!
Lupus nephritis (LN)
Renal complication of SLE.
Clinical features:
1. Usually presents with nephritic pattern of disease: hematuria, hypertension
2. Renal dysfunction: Gradual/ rapidly progressive in nature.
Types:
Grade Name
Grade 1 Minimal mesangial
Grade 2 Mesangio-proliferative
Grade 3 Focal
Grade 4 Diffuse
Grade 5 Membranous
Each stage can be further divided into: ●Acute ● Chronic ● Acute on chronic (A/C).
Investigation:
CBC, CRP USG KUB
Urea, Creatinine, Na+, K+ Renal biopsy
Blood C/S Serum autoantibodies:
ASO titre: Not high  ANA
Urine: Routine and microscopic examination  Anti-ds-DNA.
Treatment:
1. Supportive: For renal dysfunction
2. Definitive:
 Corticosteroid
 Immunosuppresents: Cyclophosphamide/Mycophenolate/Azathioprine/Tacrolimus.
Microalbuminuria
Microalbuminuria is defined as excretion of 30–300 mg of albumin per 24 hours
Spot Collection/Urinary ACR 24-hr urine Collection Category
Less than 30 mcg/mg creatinine Less than 30 mg Normal
30-300 mcg/mg creatinine 30-300 mg Microalbuminuria
More than 300 mcg/mg creatinine More than 300 mg Clinical albuminuria
Etiologies: Early proteinuria of any cause-
 DM  Urinary tract infection
 Glomerulonephritis  Marked hypertension
 Acute hyperglycemia  Congestive heart failure
c/f
1. Usually asymptomatic during microalbuminuric stage
2. Features of an underlying disease- often present
Investigations
1. Urine R.E & BM.E- apart from protein, Pus cells/RBC casts etc. may be + depending on the underlying cause
2. 24 hour urinary Albumin estimation OR Spot sample urine for ACR
3. FBG/PPBG/HBa1C/ANA/C3/ANCA-to look for an underlying cause
4. Renal Biopsy if no obvious cause can be identified from preliminary investigations
Treatment
1. For Proteinuria- ACE-i/ARB
2. BP control
3. Specific Rx of the underlying condition
Drugs and kidney
Some drugs are excreted entirely by the kidney, but most undergo metabolic transformation and may be eliminated by
non renal routes. Renal clearance is a combination of glomerular filtration and tubular secretion.
Spectrum of drug induced kidney disease
 Hypertension  Obstructive uropathy
 Sterile pyuria  Renal salt wasting
 Acute nephritis  Nephrogenic diabetes insipidus
 Fanconi syndrome  Hyperkalemia
 Nephrotic syndrome  Pre-renal azotemia
 Renal tubular acidosis  Chronic renal failure
 Acute renal failure
Treatment
1. Withdrawal of offending agent
2. Volume replacement
3. Correction of metabolic abnormalities, e.g. acidosis, hypercalcemia, hyperuricemia.
4. Identification and correction of confounding factors, e.g. arterial and/or venous insufficiency
5. Modify dose according to pt’s GFR
Cardio renal syndrome
Cardiorenal syndrome is an umbrella term that defines disorders of the heart and kidneys whereby acute or chronic
dysfunction in one organ may induce acute or chronic dysfunction of the other
Types
Type 1/ Acute- Abrupt worsening of cardiac function leading to kidney injury eg, acute cardiogenic shock or acute
decompensation of chronic heart failure
Type 2/ Chronic- Long-term abnormalities in cardiac function leading to progressive chronic kidney disease
Treatment- depends on exact type however following are different treatment options.
Diuretics – 1. Loop: Furosemide. 2. Aldo antagonist: Spironolactone, Eplerenone
ACE inhibitors or ARBs
Vasodilators: Nitroglycerin/ Nitroprusside/ Nesiritide
Inotropes
RRT: hemofiltration/hemodialysis
Cardiac resynchronization- Biventricular pacemaker
Asymptomatic bacteriuria (ABU)
Diagnostic criteria
Women - 2 consecutive specimens with at least 105 colony-forming units (cfu) per mL of the same bacterial species
Men - a single specimen with at least 105 cfu/mL of a single bacterial species
Catheterised urine specimen - a single bacterial species of at least 100 cfu/Ml
Management
Treatment of ABU is not clinically beneficial except
 In pregnant women, for whom ABU carries significant risks and treatment provides important benefits
 Children aged 5-6 years Before an invasive genitourinary procedures
Renovascular hypertension
Renovascular hypertension is an elevated BP due to anatomically evident arterial occlusive disease of the kidney(s)
Etiology:
1. Atherosclerotic disease
2. Renal artery stenosis due to Fibromuscular dysplasia (FMD) or other congenital disorders.
3. Rare causes:
 Cholesterol embolic disease
 Acute arterial thrombosis or embolism
 Arterial aneurysm
Pathophysiology: Renal ischemia initiates hypersecretion of renin, which accelerates conversion of angiotensin I to
angiotensin II and enhances adrenal release of aldosterone. The result is profound angiotensin-mediated
vasoconstriction and aldosterone-induced sodium and water retention
C/F
1. Asymptomatic with hypertension may be discovered during routine examination or preparation for surgical
treatment of another problem.
2. BP related non-specific manifestations:
 Headache.
 Neurologic symptoms: altered mental status, vision changes, vomiting, seizures, coma, encephalopathy
3. Target organ damage: Particularly if hypertension has been unrecognised/not adequately controlled
● Symptoms & sings of congestive heart failure ● Symptoms & sings of Renal failure
Investigations:
CBC
Urea, Creatinine, Na+, K+
Urinalysis
Plasma renin activity (PRA): Elevated
Imaging:
1. Doppler ultrasonography of the kidneys and abdomen, which is useful in identifying renal disease and
2. Renal Arteriography (Angiography)
Treatment:
1. Antihypertensive: most effective: ACE-i/ARB which minimizes the ischemia-induced rise in angiotensin production
2. Interventional: 1. Percutaneous transluminal angioplasty (PTA) 2. Surgical revascularization 3. Nephrectomy
Sterile pyuria/Pyuria
Pyuria literally means urine with pus. It is clinically defined as the presence of (>10 WBCs) or more neutrophils per
high power field of voided urine caught midstream.
Pyuria happens when inflammation in the urinary system increases the white blood cell numbers in the urine.
Serile Pyuria: Pyuria Without Bacteriuria
Differences Between Pyuria and Bacteriuria
Pyuria is the presence of white blood cells (>10 WBCs) per high power field) which causes pus sufficient enough to
produce cloudy or milky urine. Whereas, bacteriuria is defined as the presence of >1 × 105 CFU/mL bacteria in two
consecutive samples of urine.
Symptoms of Pyuria/ Serile Pyuria
 Cloudy or milky urine
 Foul-smelling urine
 Frequent urgent need to urinate
 Discomfort on urinating
 Fever
Pyuria Causes/ Serile Pyuria
 Urinary Tract Infection (UTI)
 Sexually transmitted infectious disease: Chlamydia, Gonorrhea
 Infection of the prostate
 Other infections: tuberculosis, anaerobic bacteria, actinomycosis, fungal infections
 glomerulonephritis, lead nephropathy, secondary syphilis
 Benign or malignant tumors in the urinary system
 Stones of the kidney, ureter or bladder
 Mechanical trauma
 Pregnancy
Tests:
1. Urinalysis / Urine Routine examination.
2. Culture of urine: RESULT MAY BE +/-
3. USG KUBP kidneys may be performed in order to identify kidney abnormalities or infection.
4. CT KUB/ IVU
Treatment for Pyuria
Sterile pyuria, or asymptomatic pyuria in the absence of infection, does not really require treatment. Individuals with
UTI undergo antibiotic therapy. If there will be no response after series of medication, further evaluation is
recommended to target the proper treatment needed.
Medications: Antimicrobial (for infection)
Prevention of Pyuria
 Good personal hygiene is the key to prevent urinary tract infections, hence pyuria. After urination or defecation,
wipe the vaginal and anal area from front to back. There are more microorganisms found in the anal area. Wiping
from front to back minimizes the chance of spreading these microorganisms to the vaginal and urethral areas.
 Wash or shower before and after having a sexual intercourse.
 Drink plentiful of water. This helps to flush the bacteria out of urinary system as it dilutes urine.
Rheumatology
Rheumatoid Arthritis
chronic multisystem disease characterized by deforming Arthropathy +/- Extra articular manifestations
C/F
1. A- articular- Pain+ stiffness+/- deformity
a. Site- small joints typically- PIP, MCP, wrist, however large joints like elbow, ankle, knee can also be affected
b. Pain with stiffness- stiffness is most prominent in the morning and often diminishes as the day progresses.
Duration of stiffness in one of the clinical indicator of severity of the disease
c. Pattern of involvement- often bilaterally symmetrical
d. O/E- affected joints are often swollen, hot, and tender particularly during an active disease
e. Deformity- ≥ of the followings can occur
1. Z deformity- Radial deviation of the wrist with ulnar deviation of the digits
2. Swan neck- Hyperextension of the PIP with Hyperflexion of the DIP
3. Boutonniere deformity- PIP flexion with DIP hyperextension
f. Functional impairment/disability mainly due to deformity + to an extent due to severe pain
2. Extra articular manifestation……..(Short notes)
Blood- Anemia can be due to- a. Anemia of chronic disease b. drug induced
Constitutional- fever+ malaise+ wt loss+ appetite loss
CVS-not common- Pericarditis/Pericardial effusion/Myocarditis/ Myo. ischaemia due to Coronary vasculitis
Chest- Pleural effusion/ interstitial fibrosis/ rheumatoid nodules/ organizing pneumonia.
(Methotrexate therapy can induce interstitial fibrosis)
CNS- Not common- a. Entrapment Neuropathy- Carpal Tunnel Syndrome
b. Compressive Myelopathy due to subluxation of Atlanto – axial or midcervical joints
Dermal-
1. Subcutaneous nodules (rheumatoid nodules) often over pressure points eg, olecranon particularly in patients whose
RF value is abnormal
2. Cutaneous Vasculitic lesions- palpable purpura or skin ulceration
3. Palmar erythema
4. Pyoderma gangrenosum
Eye- Keratoconjunctivitis/episcleritis/uveitis/nodular scleritis that may lead to scleromalacia
Felty’s syndrome- Seen in some seropositive RA characterized by the triad of RA, splenomegaly & granulocytopenia.
Although many patients with FS are asymptomatic, some develop serious and life-threatening infections secondary to
granulocytopenia.
GI- rare
Glomerular- Kidneys usually are not affected by RA, involvement can be due to NSAID/Gold/Cyclosporine
Investigation- 5 main types of tests-
1. Markers of inflammation 4. Radiography
2. Hematologic parameters 5. Joint aspiration
3. Immunologic/Serological parameters
a. Markers of inflammation- ESR and the CRP level are associated with disease activity
b. Hematologic parameters -FBC- Hb – N/ Low- due to a. chronic disease b. Blood loss due to NSAID c. DMARDs
Thrombocytosis - common and is also associated with disease activity
Leucocytosis may occur but is usually mild
Leukopenia may be a consequence of therapy or a component of Felty syndrome
c. Immunologic/Serological parameters
1. Rheumatoid factor (RF): RF titre somewhat correlates with disease activity, though titres of RF can remain high
even in patients with drug-induced remissions. RF is not specific for RA.
2. Anti−cyclic citrullinated peptide (Anti-CCP)
3. Anti−mutated citrullinated vimentin (Anti-MCV)
Anti-CCP antibodies suggest a sensitivity and specificity better than those of RF. The sensitivity of anti-MCV assays
has been reported to be comparable to that of ACP, however, other studies have found the specificity of anti-MCV to
be slightly lower than that of Anti-CCP.
4. ANA- often positive
d.Radiography
1. Xrays- remains the first choice for imaging in RA; Views of the hands, wrists, knees, feet, elbows, shoulders, hips,
cervical spine, and other joints may show erosions/osteopenia
2. MRI- more accurate assessment and earlier detection of lesions than X-rays however, the cost of the examination
and the small size of the joints involved precludes its widespread use.
e.Joint aspiration- helps to rule out coexistent infection or crystal arthritis in an acutely swollen joint.
Treatment: 1. Nonpharmacologic treatments 2. Pharmacological 3. Surgery
1. Nonpharmacologic treatments- Exercise/Physiotherapy/Massage/Counselling for stress reduction
2. Medications- include
A.Anti-inflammatory drugs-
1.NSAIDs- COX 2 (-)ors…Etoricoxib/ Non selective COX(-)ors…Ibuprofen/Aceclofenac/Diclofenac
2.Corticosteroids- Prednisolone or others- often used as a bridge to control disease activity until DMARDs become
effective OR as adjunctive therapy with DMARDs for severe disease
B. DMARDs-
1. Nonbiologic- Methotrexate, Sulfasalazine, Leflunomide, Hydroxyxchloroquine
2. Biologic- a.TNF inhibitors- ● Inﬂ iximab ● Adalimumab ● Golimumab ●Etanercept
b. Non- TNF inhibitors: ● Rituximab ● Abatecept ● Tocilizumab
3. Surgery- Synovectomy/ Tenosynovectomy/Tendon realignment/Reconstructive surgery or Arthroplasty
Principles of pharmacotherapy
 Early therapy with DMARDs
 Patients with active disease should be monitored every 3 months, and treatment should be adjusted if there is no
improvement at 6 months
 Methotrexate- recommended first-line therapy; Sulfasalazine or Leflunomide can be substituted/added if there are
contraindications/ineffective to MTX
 Biologics should be combined with DMARDs- All biologics are considered to be similarly effective
Treatment strategies The exact strategy depends on disease activity+ treatment response+ adverse effects of drugs
1. Early RA (< 6 m)- following treatment strategies
 DMARD combination therapy in moderate or high disease activity and poor prognostic features
 Anti-TNF agent ± MTX in those with high disease activity and poor prognostic features
2. Established RA(> 6 m)- following treatment strategies
 Initiating and switching among nonbiologic DMARDs
 Switching from nonbiologic to biologic DMARDs
 Switching among biologic agents because of lack or loss of benefit
 Switching among biologic agents because of adverse effects
Rheumatoid Hand……Short notes
1. Articular- Pain+ stiffness+/- deformity
a. Site- small joints typically- PIP, MCP, wrist, however large joints like elbow, ankle, knee can also be affected
b. Pain with stiffness- stiffness is most prominent in the morning and often diminishes as the day progresses.
Duration of stiffness in one of the clinical indicator of severity of the disease
c. Pattern of involvement- often bilaterally symmetrical
d. O/E- affected joints are often swollen, hot, tender particularly during an active disease
e. Deformity- ≥ of the followings can occur
1. Z deformity- Radial deviation of the wrist with ulnar deviation of the digits
2. Swan neck- Hyperextension of the PIP with Hyperflexion of the DIP
3. Boutonniere deformity- PIP flexion with DIP hyperextension
f. Functional impairment/disability mainly due to deformity + to an extent due to severe pain
2.Entrapment Neuropathy- Carpal Tunnel Syndrome
3.Subcutaneous nodules (rheumatoid nodules) often over pressure points eg, Olecranon particularly in patients whose
RF value is abnormal
4.Cutaneous vasculitic lesions- palpable purpura or skin ulceration
5.Palmar erythema
Short notes…….Autoantibodies in RA
1.Rheumatoid factor (RF)…..(Short notes)
It’s an IgM antibody directed against the Fc fragment of IgG that is present in many but not all patients with RA over
the course of their disease. RF and IgG join to form immune complexes that contribute to the disease process. RF titre
somewhat correlates with disease activity, though titres of RF can remain high even in patients with drug-induced
remissions.
RF is not specific for RA but is also present in
1.Connective tissue diseases – SLE/Scleroderma/ Sjogren’s
2.Infections- Hep B/TB/Leprosy/Syphilis
3.Autoimmune diseases- PBC/Idiopathic Pulmonary Fibrosis/Sarcoidosis
4.some healthy people.
2.Anti−cyclic citrullinated peptide (Anti-CCP)
3.Anti−mutated citrullinated vimentin (Anti-MCV)
Anti-CCP antibody has a sensitivity and specificity better than RF, presence of both Anti-CCP antibodies and RF is
highly specific for RA. Additionally, the presence of Anti-CCP antibodies indicates a worse prognosis.
Sensitivity of anti-MCV assays has been reported to be comparable to that of Anti-CCP, however other studies have
found the specificity of anti-MCV to be slightly lower than that of Anti-CCP.
4.ANA- often positive
Scleroderma/Systemic Sclerosis
Disorder characterized by progressive fibrosis of skin and internal organs.
Types
1.Diffuse Systemic Sclerosis
2.Limited Cutaneous Sclerosis (CREST syndrome)
3.Localised Cutaneous Sclerosis (Morphea)
C/F
Articular- Polyarthralgia- small joints mainly
Blood-Anaemia
CVS- RHF due to severe PAH
Pericarditis
Myocardial fibrosis leading to conduction disturbance
Chest- Diffuse Parenchymal Fibrosis
Pulmonary vascular fibrosis leading to increasing PAH
Constitutional- fever+ malaise+ wt loss+ appetite loss
CNS-××
Dermal- usually develop before visceral disease…….(commonest manifestation)
a) Initially swelling due to nonpitting oedema
b) Progressive fibrous thickening of the skin which become tightly bound to underlying subcutaneous tissue
with loss of skin folds- hall mark of the disease.
c) Sclerodactyly- localized thickening and tightness of the skin of the fingers or toes
d) Pigmentation or depigmentation
e) Telangiectasia- dilated capillaries- finger tips/lips/tongue/buccal mucosa
f) Raynaud phenomenon- often the initial manifestation of the disease
g) Digital ischemia leading to ulceration/digital infarcts
h) Calcinosis cutis
Eye- Dry eye/Keratoconjunctivitis Sicca
F-××
GI- Oesophageal dysmotility- Dysphagia/Reflux
Intestinal hypomotility- Constipation/distension/bloating/fecal impaction
Intestinal Diverticular disease
Glomerular: Acute Kidney injury (AKI) with accelerated hypertension
Scleroderma Renal crisis- may lead to permanent renal damage due to severe renovascular hypertension
resulting from intimal proliferation and fibrosis of small renal artery/arterioles
Investigation
1.FBC- Anaemia- mild often present 2.ESR/CRP- often NOT raised
3.Autoantibodies- 2 different types may be detected depending on the type of the disease
a. Anti Scl-70- Diffuse disease mainly
b. Anti-centromere antibody- Limited disease
4. Urine- Proteinuria in cases of Renal involvement
5. Urea/Cr- high in pts with renal damage
6. Chest imaging- may show Pulmonary fibrosis
7. Echo- To detect PAH
Treatment Entirely symptomatic/supportive
Problem Treatment
1.Raynaud phenomenon- Nifedipine/Losartan/Sildenafil
2.Cutaneous disease- Penicillamine
3.Oesophageal involvement Small meals/liquid or paste diet/PPI
4. PAH- Bosentan/Sildenafil/Prostaglandin
5.Hypertensive crisis ACEi
6.Pulmonary fibrosis Cyclophosphamide
CREST Syndrome- short notes
It is basically the limited variety of Scleroderma and is characterized by following features-
C-Calcinosis cutis
R-Raynaud phenomenon
E-Esophageal dysmotility
S-Sclerodactyly
T-Telangiectasia
Investigation Anti-centromere antibody
Treatment Entirely symptomatic/supportive
1.Raynaud phenomenon- Nifedipine/Losartan/Sildenafil
2.Cutaneous disease- Penicillamine
3.Oesophageal involvement Small meals/liquid or paste diet/PPI
Raynaud phenomenon…short notes
Raynaud phenomenon manifests as recurrent vasospasm of the fingers and toes
Types
1. Primary/Raynaud disease-vasospasm alone, with no association with another illness
2. Secondary-vasospasm associated with another illness/condition-
 Autoimmune diseases- Systemic sclerosis/ Mixed connective-tissue disease/SLE/APLA
 Frequent use of vibrating tools such as jackhammers and sanders
C/F
1. Vasospastic episodes provoked by cold temperatures or emotional stress. Episodes usually affect the fingers and
toes but may rarely affect the nose, ears, nipples or lips.
2. Numbness and pain in the affected area(s)may be present.
3. Affected areas also show at least two colour changes: white (pallor), blue (cyanosis), and red (hyperaemia). The
colour changes are usually in the order noted, but not always. These changes are usually reversible but may, in severe
cases, lead to local ischemia and ulceration.
4. Any history of associated symptoms should raise suspicion of an underlying disorder.
Investigations- Diagnosis is mainly on clinical ground however laboratory testing may be performed to assess for
conditions that can mimic Raynaud phenomenon or cause secondary Raynaud phenomenon.
Treatment
1. Drugs- Commonly used agents- 1.CCB- Nifedipine 2. Vasodilator- Iloprost
Other agents used- topical Nitroglycerin; SSRI-Fluoxetine; Phosphodiesterase-5 inhibitors- Sildenafil;
Endothelin antagonist-Bosentan; ARB- Losartan
2. For primary Raynaud phenomenon, the first line of therapy consists of lifestyle measures, such as avoidance of
precipitating factors and use of gloves.
SLE
Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that has protean manifestations and follows a
relapsing and remitting course.
C/F- SLE is a chronic autoimmune disease that can affect almost any organ system; thus, its presentation and course
are highly variable, ranging from indolent to fulminant.
Articular- Symmetrical, non erosive, usually non deforming arthritis affecting PIP, MCP, Wrist
Rarely deforming arhtropathy due to capsular subluxation- called Jaccourd’s arthropathy
Blood- Variable cytopenias which may be symptomatic or asymptomatic: leukopenia and/or anemia and/or
thrombocytopenia
Constitutional- fatigue, fever, appetite loss, weight loss
Chest- 1. Pleurisy 2. Pleural Effusion 3. Parenchymal/Interstitial Lung disease
Cardiac- 1. Pericarditis 2. Pericardial Effusion 3. Myocarditis
CNS-
Higher function- Depression/Psychosis/Confusion
CVA- due to cerebral vasculitis
Myelopathy- due to spinal vasculitis
Neuropathy- Peripheral or Cranial nerve damage
Dermatological
1.Photosensitivity
2.Photosensitive malar rash- non-scaly, non-scarring erythematous flat/slightly raised rashes typically over the check,
nose, chin and ears- also called butterfly rash
3.Discoid rash- circular, scaly scarring with raised rims typically over scalp, eyelids & other sun exposed parts
4. Alopecia
5.Livedo reticularis- mottled reticulated vascular pattern appearing as a lace-like purplish discoloration of the skin-
discoloration is caused by swelling of the venules owing to obstruction of capillaries by small clots.
6. Cutaneous vasculitis- leading to palpable purpura/nail fold or digital infarcts/gangrene/ulceration
Eye-
Lacrimal system disease- Dry eye syndrome (keratoconjunctivitis sicca)
Anterior segment disease- Recurrent corneal erosions; Episcleritis and scleritis
Posterior segment disease- Retinal disease- Lupus Retinopathy
Neuro-ophthalmic disease- Optic nerve disease- Optic neuritis & Ischaemic optic neuropathy
F××
Glomerular- Acute nephritic disease
Acute or chronic renal failure
GI- Oral ulcers, nausea, dyspepsia, abdominal pain
Hypercoagulability- if associated with APLA syndrome- arterial/venous thrombosis + (recurrent) miscarriage
Investigation-
1.To confirm the disease- Autoantibodies
a.ANA- sensitive but not specific, therefore best initial screening test as negative result virtually r/o SLE
b.Anti ds-DNA- Specific but not sensitive
c.Anti-smooth muscle antibody( Anti-Sm)- Specific but not sensitive
2. To look for organ complication+ to assess activity of the disease
a. FBC-variable cytopenias
b. ESR- often raised
c. CRP- usually raised if active serositis eg. Pleurisy/pericarditis/infection
d.Ur/Cr- to assess renal function
e.Urine R/E- RBC cast/Proteinuria- Lupus nephritis
f.Serum Complement level- Hypocomplementemia suggests active disease
g.Lupus anticoagulant+ Anti cardiolipin antibody- + in APLA syndrome
h. Chest radiology
Treatment- often directed against specific problems
1.Cutaneous disease- sunscreen lotion/cream
Topical corticosteroid
Hydroxychloroquine
2. Arthropathy- NSAID
Hydroxychloroquine
3.Certain problems warrant Rx with Corticosteroid-
 1.Lupus Nephritis
 CNS involvement
 Pericadrditis/Myocarditis
 Hemolytic Anaemia
 Immune thrombocytopenia
4. CNS lupus- Corticosteroid
Steroid resistant/non responsive cases- Azathioprine, Mycophenolate, Cyclophosphamide
5.Lupus Nephritis- Corticosteroid
Steroid resistant/non responder- Azathioprine, Mycophenolate, Cyclophosphamide
Belimumab
6. APLA- Anticoagulation
Antibodies in SLE…short notes
1. ANAs- sensitive but not specific, therefore best initial screening test as negative result virtually r/o SLE
2. Anti-double stranded DNA (anti-dsDNA) antibodies- Specific but not sensitive
3. Anti-Smooth Muscle antibody( Anti-Sm)- Specific but not sensitive
4. Anti-histone antibodies- Drug induced SLE
5. Anti-Ro
6. Anti-La
5. Lupus anticoagulant+ Anti Cardiolipin antibody- in APLA syndrome
Method of detection
The two most common methods used are indirect immunofluorescence and enzyme-linked immunosorbent assay
(ELISA). Following detection of ANAs, various subtypes are determined.
Antinuclear antibodies (ANAs)….short notes
Antinuclear antibodies (ANAs)/ Antinuclear factor (ANF) are a group of autoantibodies that bind to contents of the
nucleus of the cells.
ANA subtypes- Each of these antibody subtypes binds to different proteins or protein complexes within the nucleus.
1. Antibodies to Extractable nuclear antigens (ENA): ENAs are a group of autoantigens that were originally identified
as antibody targets in people with autoimmune disorders. They are termed ENA because they can be extracted from
the cell nucleus with saline. Antibodies to ENAs include-
 Anti-Smooth Muscle antibody (Anti-Sm)-SLE
 Anti-nuclear Ribonucleoprotein (Anti-nRNP)-SLE, Mixed Connective tissue disorder
 Anti-Scl-70- Scleroderma
 Anti-Jo-1- Polymyositis/Dermatomyositis
 Anti-Ro/AntiSS-A and Anti-La/Anti SS-B-Sjogren’s
2. Anti-double stranded DNA (anti-dsDNA) antibodies- SLE
3. Anti-histone antibodies- Drug induced SLE
4. Anti-centromere antibodies- CREST syndrome
Method of detection
The two most common methods used are indirect immunofluorescence and enzyme-linked immunosorbent assay
(ELISA). Following detection of ANAs, various subtypes are determined.
Seronegtive Spondyloarthropathy
Group of inflammatory arthritis with predilection for spine+sacroiliac joint & absence of any autoantibodies.
The group includes-
1. Ankylosing Spondylitis 4. Inflammatory Bowel disease associated arthropathy
2. Reiter Syndrome 5. undifferentiated Spondyloarthropathy
3. Psoriatic arthropathy
Ankylosing Spondylitis
Chronic inflammatory arthropathy mainly affecting joints of the axial skeleton
C/F……it’s “A” disease!!!!
Age- usually starts in late teens or early 20s
Arthopathy-
1. Axial joints mainly
2. Ascending involvement of the spine – therefore starts typically with low back pain & stiffness
3. Activity- usually improves pain and stiffness( this is a character of most of the inflammatory arthropathies)
4. Axial joint movement slowly become restricted
5. Ankylosis- is a stiffness of the spine due to abnormal adhesion and rigidity of the bones of the joint
6. Advanced cases- Entire spine becomes fused and does not allow movement in any direction
7. Acute arthritis- occasionally transiently affect peripheral joints
Extra articular manifestations-
1. Anterior Uveitis
2. Aoritic root dilatation- leading to AR
3. AV conduction disturbance
4. Apical Fibrosis of lungs
5. Achillis Tendonitis-heel pain
6. IgA Nephropathy
Investigation- No confirmatory test
1. Imaging- Xray/MRI shows characteristic changes in advanced cases
2. Blood- Mild Anaemia
3. ESR- raised
4. Autoantibodies- Negative
5. HLA-B27- Strongly associated with Ank. Spond BUT not a specific/sensitive/confirmatory test
Treatment
1. Nonpharmacolgical therapy- Exercise/Physiotherapy
2. Pharmacological
a. NSAID- for pain relief
b. Steroid- No role
c. Sulfasalazine- effective for Peripheral Arthropathy but minimal impact on axial disease
d. Biological agents- Infliximab/Golimumab/Adalimumab- for NSAID resistant cases
Reiter Disease/syndrome (Reactive Arthritis)
Reactive arthritis is an autoimmune condition that develops in response to an infection in another part of the body
(cross-reactivity)
C/F- triad of Urethritis + Conjunctivitis + Arthritis (age old mnemonic ‘’can’t pee, can’t see, can’t climb a tree’’)
1. Antecedent GI infection(diarrhoea) or STD (per urethral discharge) often present in recent past- most cases develop
1-4 weeks after GI/Sexually transmitted infection
2. Arthritis- asymmetric involvement of Knees, ankles
Sacroilitis
3. Conjunctivitis- usually mild. Anterior uveitis is a more significant ocular problem
4. Urethritis-Dysuria or an increased frequency of urination.
Other urogenital problems- prostatitis, cervicitis, salpingitis and/or vulvovaginitis
5. Mucocutaneous- Balanitis/stomatitis/Keratoderma Blenorrhagicum - small hard nodules called keratoderma
blennorrhagicum on the soles of the feet and, less commonly, on the palms of the hands
6. Those with a prolonged course of the disease, will develop cardiac manifestations, including aortic
regurgitation and pericarditis
Investigation
Imaging of the joints-may show some changes in chronic cases
Treatment
1. NSAID
2. Disease not responding to NSAID- Sulfasalazine/Methotrexate
3. Biological agents- Infliximab/Golimumab/Adalimumab- for severe cases
Psoriasis
A chronic, noninfectious, inflammatory papulosquamous skin disease
Etiology exact cause not known. Genetic factors probably play some role.
Triggering factors: Stress, infection (strepto), drugs(Antimalarial/Beta blocker/Lithium)
C/F- 1.Skin 2. Nail 3. Joints- can be affected

Skin
1. Dry,well defined,erythematous macular/papular lesions with silvery scales+/- plaques
2. Typically over Extensor aspect of elbows & knees/scalp/behind ears
3. flexural surface like axilla/groin/submammary areas
4. Mucosal involvement- very rare
5. Itching absent
6. Auspits sign-pinpoint bleeding when scales are removed
7. Koebner phenomenon-Appearance of new lesions along the scratch line/areas of scarring
Types- Plaque/Guttate/Erythrodermic/Inverse/Pastular
Nail changes 1. Pitting
2. Beau's lines (horizontal ridging)
3. subungual hyperkeratosis and
4. Onycholysis (separation of nail from nail bed)
Arthropathy- Pain/swelling/stiffness of the affected joint(s). Psoriatic arthritis may remain mild, or may progress to
more destructive joint disease. Periods of active disease, or flares, will typically alternate with periods of remission
Types
1. Asymmetrical Oligoarthritis/Monoarthritis-involving DIP(most common) but/PIP/MCP/Wrist/feet jts/ankles may be
affected
2. Symmetrical seronegative small joint polyarthitis
2. Spondyloarthropathy- Sacroiliac jt
3. Arthritis mutilians- severe destructive and deforming arththropathy
4 Enthesopathy-Pain in and around the feet and ankles, especially tendinitis in the Achilles tendon or plantar
fasciitis in the sole of the foot.
Investigation
1. Skin and nail changes are diagnosed clinically. Skin biopsy can be done , but is rarely required
2Arthropathy- Serological tests like ANA/RA factor/Anti CCP- to rule out other small joint arthropathy
Treatment
Skin disease
1. Topical Rx
1. Psoralen + Ultraviolet A phototherapy= PUVA
2. Retionoid
3. Coal Tar
4. Vit D analogues-paricalcitol/ calcipotriol
2. Systemic Rx
Non biological- Methotrexate, Ciclosporin, Hydroxycarbamide, Retinoids
Bioligical- Infliximab, Adalimumab, Golimumab, Certolizumab, Etanercept
Arthropathy
1. NSAIDS
2. Non biological- Methotrexate/Leflunomide/cyclosporin/azathioprine/sulfasalazine.
3.Biological- Infliximab/Etanercept/Golimumab/Adalimumab/Certolizumab/ Ustekinumab
Gout
It’s a crystal arthropathy characterized by recurrent attacks of acute inflammatory arthritis.
Etiology/Types………. (SN: Hyperuricemia)
1. Primary 2. Secondary
a. Increased urate production a. Increased production
1. Idiopathic 1. Myeloproliferative disorders
2. Enzyme defect disease 2. Lymphoproliferative disorders
b. Decreased urate excretion b. Decreased excretion
1. Idiopathic 1. CKD
2. Drug induced- Thiazides
C/F
1. Acute monoarticular Gout
a. Onset- Sudden
b. Precipitating factors- High purine diet/Alcohol/Thiazides/Surgery/Rapid Fluctuation of urate level
c. Description of an episode- Excruciating pain typically in the 1st MTP joint. Other joints, such as the heels, knees,
wrists, and fingers, may also be affected. Joint pain usually begins over 2–4 hours and during the night.
d. Pain is often accompanied by fever and pruritus of the overlying skin.
e. O/E- affected joint is red, hot, swollen, tender, movements restricted with dusky red appearance of the overlying
skin which often excoriates.
f. Attacks may be recurrent if not treated properly with asymptomatic intervals between episodes
2. Chronic Tophaceous Gout- characterized by Monosodium urate deposition in articular and extra-articular sites.
a. Articular- chronic pain and even deformity
b. Pinna, extensor surface of arm- often becomes palpable with firm/hard nodular consistency, in some pts they
ulcerate with release of white gritty material
c. Urolithiasis- Urate stone in the kidney/ureter causing acute loin pain or ureteric colic
d. Urate Nephropathy- may lead to Renal impairment
Investigation
1. Serum Uric Acid level- often high, however a normal uric acid level does not exclude Gout
2. TC/ESR- often mildly raised during an acute episode
3. Identification of Monosodium urate crystal in Joint fluid aspirate/ tophus
4. Xray- often normal in early disease, abnormal in advanced disease
Treatment
1. Treatment of acute episode-
a. NSAID
b. Colchicine
c. Corticosteroid- rarely required- main indication is absolute contraindication using NSAID or Colchicine
2. Treatment to prevent recurrence of acute episode/ Treatment Chronic Gout
a. Dietary modification- Avoid high Purine diet- All meats/Alcohol/Lentil/Cauliflower/Spinach/mushroom
b. Drugs- Urate Lowering drugs- Indications are a. frequent acute arthritis b. Tophaceous deposit c. CKD
1. Xanthine Oxidase inhibitors- Allopurinol; Febuxostat
2. Uricosuric agent- Probenecid…rarely used now a days
3. Uricase- rarely indicated for Pts with refractory tophaceous gout
Pseudogout
It is a crystal-induced arthropathy caused by Ca pyrophosphate crystals (CPP disease)
C/F:
Acute arthritis- Podagra/involvement of 1st MTP
Arthritis of other joints – large joints- knee, wrist, elbow, or ankle
Monoarticular involvement most commonly, though acute polyarticular attacks are not rare, and different joints may
be involved simultaneously or in rapid succession
Attacks resemble those of acute gout or a more insidious onset that occurs over several days
In some cases, eventual development of chronic polyarticular arthritis that can resemble rheumatoid arthritis
Involvement of a single (most common) or multiple joints with signs of inflammation– Swelling, warm, erythema and
tenderness +/- Fever
Investigations
Joint fluid aspiration-Microscopic analysis in shows CPP crystals- under a polarizing filter- rhomboidal, positively
birefringent and appears blue. Fluid WBC count may be high but Culture is negative.
Treatment NSAID/Rest/Physio
Vasculitis
A group of disorders characterized by inflammation of wall of the vein, arteries and capillaries.
Classification:
Large vessel vasculitis
 Takayasu arteritis
 Giant cell arteritis
Medium vessel vasculitis
 Polyarteritis nodosa (PAN)
 Kawasaki disease
Small vessel vasculitis: “presence/absence” of ANCA & Immune complex deposition in the affected organs
1. AntiNeutrophil Cytoplasmic Antibody (ANCA)–associated vasculitis/Pauci- Immune Vasculitis
 Microscopic polyangiitis (No immune complex deposition)
 Granulomatosis with polyangiitis/Wegener’s
 Eosinophilic granulomatosis with polyangiitis/Churg-Strauss
2. Immune complex SVV/ANCA negative Vasculitis
 Goodpasture syndrome (anti-GBM) disease
 Cryoglobulinemic vasculitis
 IgA vasculitis (Henoch-Schonlein)
 Drug-associated immune complex vasculitis
3. Vasculitis associated with systemic disease
 Connective tissue disease: Lupus vasculitis Rheumatoid vasculitis Sjogren syndrome
 Infection (infective endocarditis/ meningococcemia/ typhoid fever)
 Malignancy
There is substantial overlap with respect to arterial involvement, and an important concept is that all 3 major
categories of vasculitis (although each have a preference) can affect any size artery.
Approach to a patient of vasculitis

Principle:
1. To look for systemic manifestations
2. To look for organ specific manifestations
3. To look for underlying disease.
History:
1. Systemic manifestations: To be looked for
 Low grade fever
 Loss of appetite
 Loss of weight
 Lassitude
2. Underlying cause: To be looked for
 Infection (infective endocarditis/ meningococcemia/ typhoid fever)
 Connective tissue disease
 Malignancy
3. Organ damage/involvement : Gives an idea about underlying Connective tissue disease (CTD) as well the
specificVasculitic syndrome
Organ Manifestations Inference
CNS Headache/ seizure/ TIA/ stroke* Vasculitis asscociated with CTD
Eye Red eye/ gritty eye/ painful eye Connective tissue disorders
ENT Blocked nose/ epistaxis/ crusting/ ulceration/ ear infection Wegener’s granulomatosis
CVS Angina (coronary vasculitis) Takayasu’s disease

Asthma Churg-Strauss disease
Respiratory Sudden breathlessness ± Hemoptysis Goodpasture syndrome
Recurrent pneumonia Connective tissue disease
GIT Melena/ Post-prandial pain Intestinal ischemia
Renal Hematuria/ history suggestive of AKI/ CKD Glomerular/renal vasculitis: small
vessel vasculitis/CTD
Skin Skin rash Vasculitic rash
Joint Joint pain ± Swelling Connective tissue disease
Above questions are asked to screen for any organ involvement. Distribution of organ involvement depends upon the
underlying type of vasculitis.
4. Underlying cause:
 Infection (infective endocarditis/ meningococcemia/ typhoid fever)
 Connective tissue disease
 Malignancy
Examination:
Organ/ system Look for:
Eye Any evidence of uveitis, if present suggests Connective tissue disorders
ENT Crusting/ granulations/ septal perforation, present suggests Wegener’s granulomatosis
Skin Skin rash: Palpable purpura; Petechiae: suggestive of cutaneous vasculitis.
Typical rash for CTDs should be looked for.
CVS Signs of pericarditis/ pericardial effusion (suggestive of CTD)
Respiratory 1. Pleurisy/ pleural effusion: CTD
2. Widespread crepitations: Goodpasture
3. Focal signs of pneumonia: CTD
Joint Small joint arthritis: CTD
Investigations:
1. Blood
A. Routine investigations:
1. Full blood count: Hb↓ (due to chronic inflammation/ ongoing hematuria/ GI bleed/ alveolar hemorrhage)
2. WBC: ↑ (often ↓ in SLE)
3. Platelet: Normal
4. ESR/ CRP: ↑
B. Blood culture:
To rule out any underlying bacterial infections.
C. Urea-creatinine: To assess any renal derangement
D. Serum auto antibodies:
 ANCA (Anti-neutrophil cytoplasmic antibody):
It is of 2 types:
I. c-ANCA (Cytoplasmic pattern): Target antigen: Proteinase-3 (PR3)
+Ve in:Wegener’s granulomatosis.
II. p-ANCA (Perinuclear pattern): Target antigen: Myeloperoxidase (MPO)
+Ve in:
 Microscopic polyangitis
 Churg-Strauss syndrome.
 Anti-GBM antibody:+Ve in Goodpasture syndrome
 Anti-nuclear antibody:+Ve in SLE (Confirm with Anti-ds-DNA)
 Anti-CCP antibody/ RA factor: +Ve in Rheumatoid arthritis.
2. Urine: Routine and microscopic examination of urine: To look for: RBC/ RBC cast
3. Biopsy- To confirm diagnosis: Common site of taking biopsy: Kidney, skin.
4. Imaging
 Chest X-Ray: To look for nodules/ cavity (suggestive of Wegener’s)
 If positive: CT chest.
5. Echocardiogram: To look for infective endocarditis
6. USG-KUB: To look for any structural / functional abnormality of urinary passage.
Treatment:
Specific treatment depends upon the type of vasculitis; however, the mainstay of treatment are:
1. Corticosteroid
2. Immunosuppressant: a. Cyclophosphamide b. Azathioprine c. Rituximab d. Methotrexate
Wegener’s granulomatosis
Vasculitis characterized by necrotizing granulomatous inflammation of vessels.
Clinical features:
System Manifestations
ENT  Recurrent episodes of epistaxis/ nasal crusting/ nasal ulceration
 Recurrent otitis media
 Recurrent septal perforation.
Eye  Uveitis
Lung  Multiple cavitations/ nodules/ cavitary pneumonia
 May be asymptomatic/ may cause breathlessness/ productive cough.
Kidney  Glomerulonephritis Hematuria ± Hypertension
Limbs  Recurrent DVTs
Investigations:
1. Blood:
 Hb: ↓
 WBC: ↑
 ESR/ CRP: ↑
2. Urea creatinine: To rule out renal dysfunction
3. c-ANCA: Characteristically +Ve and a high titre is often a predictor of severe disease.
4. Urine R/E and M/E: Look for RBC cast and dysmorphic RBCs.
5. CXR ± CECT chest
6. Biopsy: Site: Lung, kidney
Treatment: Definitive: Corticosteroid, Cyclophosphamide.
Goodpasture syndrome
Vasculitis characterized by acute reno-pulmonary involvement.
Clinical features:
1. Pulmonary: Typically abrupt onset severe intra-alveolar hemorrhage; sudden shortness of breath, productive
cough; often blood mixed/ frank hemoptysis.
2. Renal: RPGN: Hematuria, hypertension +/- AKI
3. Often patient becomes significantly anemic.
Investigation:
1. Full blood count:
 Hb: ↓
 WBC: ↑
 ESR: ↑.
2. Anti-GBM antibody: +Ve
3. CXR: Diffuse bilateral alveolar opacities (resembling cardiogenic/ non-cardiogenic pulmonary edema)
4. CECT chest: If possible
5. Urine (R/E and M/E): Look for RBC, RBC cast, Dysmorphic RBC.
Treatment:
1. Supportive: Ventilatory supports
2. Definitive: Corticosteroid, Cyclophosphamide
Churg-Strauss syndrome
ANCA +Ve small vessel vasculitis.
Clinical features:
1. Background H/O asthma often present which is often difficult to control (however, cases may also develop in
non-asthmatics)
2. Mononeuritis/ Mononeuritis multiplex: Rapid damage of a motor nerve causing sudden foot drop/ ocular
cranial nerve paralysis
3. Eye: Scleritis/ Episcleritis/ Uveitis
4. Skin: Rash/ vasculitic rash
5. Kidney: Usually spared.
Investigation:
1. Full blood count: Eosinophilia
2. Autoantibody: p-ANCA +Ve.
Treatment: Corticosteroid ± Cyclophosphamide
Behçet's disease
Small and medium vessel vasculitis which has no diagnostic test.
Clinical features:
1. Buccal: Recurrent painful oral aphthous ulcer
2. Cutaneous Skin:
 Erythema nodosum like lesion
 Follicular skin rash
 Pathergy: Spontaneous blistering of venipuncture site.
3. CNS: 1. Seizure 2. Cranial nerve palsy 3. Meningitis.
4. DVT: Recurrent DVT (hypercoagulable state)
5. Eye: Posterior uveitis
6. Fever
7. Genital: Recurrent painful genital ulcer
Investigation: No diagnostic test available.

Treatment:
1. Corticosteroid
2. Colchicine
3. Thalidomide
4. Immunosuppressants: Rituximab/Cyclophosphamide
Hyponatremia(Normal Na- 135/145 mEq/L)
Hyponatremia is defined as a serum sodium level of < 135 mEq/L (severe- < 125 mEq/L).
Types and causes: 3 following categories, according to the effective intravascular volume:
a. Hypovolemic hyponatremia: decrease in total body water with greater decrease in total body sodium
Severe volume depletion secondary to GI or Renal loss, or diuretic use
b. Euvolemic hyponatremia: normal body sodium with increase in total body water
Associated with nonosmotic & nonvolume related ADH secretion- SIADH
c. Hypervolemic hyponatremia: increase in total body sodium with greater increase in total body water
Cirrhosis, CCF, Nephrotic syndrome, CKD
Symptoms & signs – Can be asymptomatic
1. Moderate Hyponatremia Severe/Acute Hyponatremia
Hiccup Altered sensorium
Nausea Behaviourial disturbance
Malaise Confusion/ Convulsion/ Coma
Lethargy Delirium
Overt neurologic symptoms most often are due to very low serum sodium levels (usually <115 mEq/L), which results
in osmotically driven movement of water from the extracellular compartment of brain into brain cells leading to
intracerebral oedema. The severity of neurologic symptoms correlates well with the rate and degree of the drop in
serum sodium. A gradual drop in serum sodium, even to very low levels, may be tolerated well if it occurs over
several days or weeks, because of neuronal adaptation to new osmotic environment.
2. Determination of volume status often guides treatment decisions.
Investigations
1.Electrolyte- Na, K 4.Serum osmolality
2.Urea, Creatinine 5.Urinary sodium concentration
3.Urine osmolality
Treatment
1. Treatment depends on the underlying types:
a. Hypovolemic hyponatremia: Isotonic saline
b. Hypervolemic hyponatremia:
 Diet: Salt and fluid restriction
 Diuretic: Loop diuretic
 AVP receptor antagonist- promotes aquaresis (ie, electrolyte-sparing excretion of free water)
 Tolvaptan - a selective V2 receptor antagonist. Oral agent
 Conivaptan- V1A and V2 vasopressin receptor antagonist. IV agent
c. Euvolemic hyponatremia:
 Free water restriction (<1 L/d)
 Correction of the underlying condition
 V2 receptor antagonist may be considered
2. Overtly symptomatic hyponatremia ( neurodeficits+)- Hypertonic (3%) Saline infusion

a. During therapy, close monitoring of serum electrolytes (every 4 h) to avoid overcorrection.
b. Goal is to increase the serum Na by approximately 0.5- 1mEq/L/h during first 48 hours and total increase should not
exceed 10-12 mEq/L/d until the neurologic symptoms subside or until plasma Na concentration is over 120 mEq/L.
c. Rapid correction of Na can ppt Central Pontine Myelinosis (spastic quadriparesis+ pseudobulbar palsy)
Hypernatremia
Hypernatremia- > serum sodium level >145 mEq/L)
Types and causes: Usually due to “free water deficit” (ie, water deficit >sodium deficit)
 Extrarenal loss - Diarrhea, vomiting, fistulas, significant burns
 Renal loss – DI, Osmotic diuretics, diuretics
Symptoms and signs-can be asymptomatic OR ≥ 1 of the followings particularly in Moderate- Severe HypeNa+
Anorexia
Altered sensorium
Behavioural disturbance
Confusion
Convulsion
Coma
Drowsiness/ Delirium
Investigations
1.Electrolyte- Na, K 3.Serum osmolality
2.Urea, Creatinine
Treatment
 When possible, providing free water to a patient orally is preferred.
 Hypernatremia should not be corrected at a rate greater than 0.5-1 mEq/L per hour during first 48 hours.
Using isotonic NaCl stabilize hypovolemic patients who have unstable vital signs before correcting free water deficits
because hypotonic fluids quickly leave the intravascular space and do not help to correct hemodynamics.
Once stabilization has occurred, free water deficits can be replaced either orally or intravenously.
Hypokalemia (Normal K+ 3.5- 5 mEq/L)

Hypokalemia is K+ level < 3.5 mEq/L. (Severe- less than 2.5 mEq/L)
Causes
1. Renal loss 2. GI loss 3.Transcellular shift
Renal tubular acidosis Diarrhoea Alkalosis
Hyperaldosteronism Vomiting or nasogastric suctioning Continuous IV Insulin infusion
Diuretics Laxative abuse Beta-agonist
Clinical manifestations
1. Due to hypokalemia: ++ 2. Due to underlying cause
may be ASYMPTOMATIC, if symptomatic, is due to Flaccidity of muscles
a. Skeletal Muscle c. Cardiac muscle: Brady or tachyarrhythmias
 weakness +/- cramp Palpitation/Syncope
 flaccidity Cardiac arrest
b. Intestinal muscle- Paralytic/adynamic ileus d. Respiratory muscle- in extreme hypokalemia: Hypoventilation
 Abdominal pain
Treatment
 Bloating
1. Mild to moderate hypokalemia (K-2.5-3.5 mEq/L)-Oral K replacement
 Constipation
therapy- KCl orally
 Distension
2. If K< 2.5 mEq/L IV KCl potassium should be given
 Emesis
3. Correct any Hypomagnesimea as K level is difficult to replenish if the
 Flatus-(+), but Feces- (-)
serum magnesium level is also low.
Investigations
4. Identify the etiology of the hypokalemia and correct/treat it
Serum K+ < 3.5 mEq/L (3.5 mmol/L)
Na, Ca2, and/or PO4 level if coexistent electrolyte disturbances are suspected
Consider ABG- Alkalosis can cause potassium to shift from extracellular to intracellular space.
Hyperkalemia
K+ > 5 mEq/L in adults. (Severe/Critical- > 6.5 mEq/L)
Causes
1. Excessive intake- Dietary excess very rare, mostly due to excessive IV or oral K supplementation (in a hypokalemic
patient)
2. Decreased Renal clearance
 Renal failure (most common)
 Medications that interfere with potassium excretion- K-sparing diuretics, ACE-i, ARB
 Addison disease
3. Decreased shift from extracellular space to intracellular: Severe Insulin deficiency as in DKA/HHS
Clinical manifestations Many are asymptomatic. High levels of potassium cause abnormal heart and skeletal muscle
function by lowering cellular resting action potential and preventing repolarization leading to muscle paralysis
1. Palpitations/Syncope due to arrhythmia. May cause sudden cardiac arrest
2. Evidence of an underlying cause may/may not be present
Investigations
1. Electrolytes- K, Na, Mg
2. ECG
3. Urea/Creatinine if high suggests renal impairment
4. Depending on initial clinical findings and results, following may be indicated
1. Glucose level - In patients with known or suspected diabetes mellitus
2. ABG - If acidosis is suspected
3. ACTH stimulation test- To check for Adrenocortical insufficiency
Management
1. Moderate elevation of K and no ECG changes
Avoid K rich diet
Binder: Na-Polystyrene Sulfonate (Increase K excretion using a K exchange resin)
Correct the cause
2. Dangerous situation: In patients with severe hyperkalemia /ECG changes present
1. Beta 2 agonist Nebulization- Salbutamol- enhances K uptake by cells
2. Calcium Gluconate IV-to counteract cardiac toxicity of K
3. Dextrose + Insulin- IV infusion to enhance K uptake by cells
4. Dialysis (urgent) for patients with renal failure
ECG abnormality of Hyperkalemia…short notes
ECG changes often have a sequential progression which approximately correlate with K level
Early: K level of 5.5-6.5 mEq/L are At a K+ level of 6.5-8.0 mEq/L At a K+level ≥ 8.0 mEq/L
 Tall, peaked T waves with a  Peaked T waves  Absence of P wave
narrow base, best seen in precordial  Prolonged PR interval  Progressive QRS widening
leads  Decreased or disappearing P  Intraventricular conduction blocks
 Shortened QT interval  Widening of the QRS  Progressively widened QRS
 ST-segment depression  Amplified R wave eventually merges with the T wave,
forming a sine wave pattern
 Ventricular fibrillation
SIADH
Defined as hyponatremia and hypo-osmolality resulting from inappropriate, continued secretion of ADH (which
results in impaired water excretion) despite normal or increased plasma volume
(ADH promotes the reabsorption of water from the tubules in the collecting ducts but it does not exert a significant
effect on the rate of Na+ reabsorption.)
Causes
1. CNS disorders-
Acute psychosis/Acute intermittent porphyria
Brain abscess
CVA/ CNS lupus/Cavernous sinus thrombosis
Delirium tremens
Encephalitis (viral or bacterial)/ Epilepsy
GB syndrome
2. Malignancies- Pulmonary - Lung carcinoma and mesothelioma/ Gastrointestinal/ Genitourinary
3. Pulmonary disorders- Bacterial pneumonia/COPD/Cystic fibrosis/ Empyema/Pneumonia (viral,fungal)/Positive
pressure ventilation/ Pulmonary abscess
4. Drugs-Anticancer/Antiepileptics/Antidepressant
Symptoms & signs – Can be asymptomatic

1. Moderate Hyponatremia Severe/Acute Hyponatremia
Lethargy Altered sensorium
Malaise Behaviourial disturbance
Nausea Cofusion Convulsion Coma
Hiccup Drowsiness
2. Volume status – No hypo or hypervolemia
Investigations- Tests help to diagnose SIADH as well as to rule out other causes of euvolemic hyponatremia
Serum Na- Low Serum cortisol- Normal
K, Cl, HCO3- normal TSH- Normal
Plasma osmolality- Low Urinary Sodium- typically more than 20 mEq/L
Urea, Creatinine- Normal (Kidney fails to conserve Na adequately inspite of
Blood glucose- Normal hyponatremia)
Serum uric acid- often low in SIADH
Treatment
1. Free water restriction (<1 L/d)
2. Overtly symptomatic hyponatremia (neurodeficits+)- Hypertonic (3%) Saline infusion
a. During therapy close monitoring of serum Na to avoid overcorrection.
b. Goal is to increase the serum Na by approximately 0.5- 1mEq/L/h during first 48 hours and total increase should not
exceed 10-12 mEq/L/d until the neurologic symptoms subside or until plasma sodium concentration is over 120
mEq/L.
c. Rapid correction of Na can ppt Central Pontine Myelinosis (spastic quadriparesis+ pseudobulbar palsy)
3. AVP receptor antagonist- promotes aquaresis (ie, electrolyte-sparing excretion of free water)
 Tolvaptan - a selective V2 receptor antagonist. Oral agent
 Conivaptan- V1A and V2 vasopressin receptor antagonist. IV agent
4 Treat / remove the underlying cause
Hypocalcemia/Tetany
Total serum calcium < 8.8 mg/dL in the presence of normal plasma protein concentrations or a serum ionized calcium
concentration < 4.7 mg/dL
Causes:
Parathyroid related causes: Hypoparathyroidism
Non parathyroid diseases:
Vitamin D deficiency
CKD
Magnesium depletion
Hyperphosphatemia
Acute pancreatitis
Massive Transfusion of blood
Clinical features: Major clinical manifestations of hypocalcemia are due to disturbances in cellular membrane
potential, resulting in neuromuscular irritability.
Asymptomatic
1. Muscle cramps involving the back and legs.
2. Insidious hypocalcemia may cause mild encephalopathy and should be suspected in patients with unexplained
dementia, depression, or psychosis.
3. Tetany characteristically results from severe hypocalcemia but can result from reduction in the ionized fraction of
serum calcium without marked hypocalcemia, as occurs in severe alkalosis.
Tetany is characterized ≥1 of the followings
 Sensory symptoms consisting of paresthesias of the lips, tongue, fingers, and feet
 Carpopedal spasm, which may be prolonged and painful
 Generalized muscle aching You will need a separate “short note” on Tetany if you are a Kid!!
 Spasm of facial musculature
 Tetany may be overt with spontaneous symptoms or latent and requiring provocative tests to elicit-
 Chvostek sign is an involuntary twitching of the facial muscles elicited by a light tapping of the facial nerve just
anterior to the exterior auditory meatus.
 Trousseau sign is the precipitation of carpal spasm by reduction of the blood supply to the hand with a
tourniquet or BP cuff inflated to 20 mm Hg above systolic BP applied to the forearm for 3 min.
Investigations
Serum Ca 2+ - Low
Serum PTH concentration
 Hypoparathyroidism: Low
 Non parathyroid diseases: Normal/High ( High: If you remember…this is Secondary
Treatment:
1. IV Calcium- Ca-Gluconate or Oral Ca-Carbonate
2. Treat the underlying cause: eg.
 Hypoparathyroidism: Recombinant Parathyroid hormone:Teriparatide
Hypercalcemia
Serum calcium > 10.3 mg/dL
Causes:
Malignancy associated Hypercalcemia
Non malignant causes
 Drugs: Taking too much of Ca+ or Vitamin D
 Sarcoidosis
 Primary Hyperparathyroidism
Clinical features:
1.“hypercalcaemic” symptoms can include:
A- Appetite loss D- dehydration
Abdominal cramp/ pain E- Excessive thirst
B- Bodyache- joint/muscleache Emesis
C- Constipation F- Fatigue
Confusion Frequent urination
Convulsion
Blood:
Serum Ca 2+ - elevated serum calcium
Serum PTH concentration-
 Primary Hyperparathyroidism: elevated
 Rest of the casues: Normal
Treatment
Supportive treatment: Management of severe hypercalcemia in the acute setting
 a. Short term/ Emergency treatment: in case of dangerous hypercalcemia/symptomatic hypercalcemia
a.IV fluid: intravascular volume expansion with sodium chloride
b.Loop diuretics: Furosemide once the intravascular volume is restored.
c.Drugs: Calcitonin and IV bisphosphonate as a temporary measure prior to surgery
 b. Long term treatment:
1.Bisphosphonates: Alendronate/Risedronate/Zolendronate, has been shown to improve the Bone Mineral
Density(BMD) in patients with chronic hypercalcemia: hyperparathyroidism and Malignancy with Bone metastasis
Definitive treatment: Treat the cause

Respiratory System
RESPIRATORY
Inspection & Palpation
Asymmetrical movement = movement restricted= underlying lung NOT expanding properly= hemithorax/ part of it
showing restricted movement is the ‘Pathological side’ however “pathology can be any 1 of these
Collapse/Fibrosis/Consolidation/Effusion/Pneumothorax
Shift: of Trachea & Apical impulse (casually called Mediastinal shift)
“Push”- shifted to opposite/contralateral side: Effusion/Pneumothorax
“Pull”- shifted to same/ipsilateral side: Collapse/Fibrosis
Shift occurs ONLY if underlying pathology is SIGNIFICANTLY “massive”- so often NO SHIFT in these situations
Percussion
Sound produced is due to air containing alveoli underneath
No sound= impaired/dull “More” sound= hyperresonant/tympanitic

 No air: Collapse/Fibrosis/Consolidation Increased air content
 Sound not getting ‘conducted’: Effusion/Thickened pleura Alveoli: Hyperinflation-Emphysema
Pleura: Pneumothorax
Auscultation
Tracheo-Bronchial breathing (”tubular“breathing) produces sound of air flowing back and forth through the tracheo-
bronchial tree- because of the tubular structure of the bronchial tree, this sound contains a number of single frequencies
giving them a somewhat “musical” quality.
So-called normal breath sound heard over the chest (coming through aerated lung), have a very “different quality”.
Firstly, air passing through progressively smaller bronchi and bronchioles results in the production of sounds
containing an increasing number of different frequencies, while the interposed alveoli with varying degrees of aeration
provide a vast quantity of tiny sound absorption units, so that sound arriving at the chest wall have lost much of
their musical character and volume.
So the sound “produced” changes its’ character (“Bronchial”) while passing through millions of aerated alveoli to
attain a different quality (“Vesicular”)
Breath sound abnormalities
Qualitative Quantitative
Bronchial breath sound over chest Vesicular breath sound- Intensity altered
Non aerated lung tissue Reduced/diminished VBS
Consolidation Air flow diminished= Air entry diminished
Collapse Complete 1. Partial non aeration: “Incomplete”Consolidation/Collapse/Fibrosis
Fibrosis 2. Airway resistance increased: COPD/Asthma
3. Non conducted surface: Effusion/Pneumothorax
VR/VF- increased VR/VF- diminished
Added sounds
Rhonchi/Wheeze:= Airway narrowing (Broncho”spasm”)
Airway remodelling “Physical” obstruction
COPD Tumor
Asthma Bilateral/scattered wheeze Mucus plug Localized rhonchi
Foreign body
Crepts/Crackles:= Moist/wet alveoli (Moist sound)
Secretion Exudate Hemorrhage Pulmonary edema
Bronchiectasis Pneumonitis Alveolar hemorrhage “fluid squeezed out” “fluid oozed out”
LVF ARDS
Chest findings (signs) of common diseases/conditions: “NO FINDINGS!!”- in EACH of these, chest examination
may be NORMAL if the underlying condition is minimal/ insignificant in “quantity/severity”
Condition Mediastinal shifting Percussion Breath sound VR/ VF Added sound(s)

Pleural  Often no shift at & below the level of effusion
effusion  Opposite: Dull VBS↓ ↓↓
massive effusion
Pneumothorax  Often no shift Entire hemithorax of the affected side
 Opposite: Tympanitic VBS↓↓ ↓↓ -
massive effusion
COPD No shift bilateral symmetrical
Hyperresonant Early stage
ONLY if Normal Normal Rhonchi- often
hyperinflated
Well established case
VBS↓ ↓↓
Asthma No shift bilateral symmetrical
Normal Early stage/Inactive Rhonchi
Normal Normal
Active disease
VBS↓ ↓↓
Consolidation No shift Over that part of the chest wall which overlies the pathology
Normal Normal Crepts
Impaired: large VBS↓ ↓↓ Crepts
consolidation ↑
BBS Crepts
Collapse No shift Over that part of the chest wall which overlies the pathology
Normal VBS↓ ↓↓
Same side Impaired: large BBS ↑
consolidation
Fibrosis Same side Over that part of the chest wall which overlies the pathology
Normal VBS↓ ↓↓ Crepts
Impaired: large
consolidation
Final Reminder!!!
EACH of these, chest examination may be NORMAL if the underlying condition is minimal/ insignificant in
“quantity/severity”
Respiratory failure Respiratory system: 3 parts:
It is defined as an arterial blood gas (ABG) PaO2<60 Lungs (gas-exchanging organ)
mm Hg and/or PaCO2 >45 mm of Hg Pump: ventilates: chest wall + respiratory muscles
Centre: Controllers in the CNS & the pathways that
connect the controllers with the respiratory muscles
(spinal and peripheral nerves).
Failure of each part of the system leads to a distinct
entity:
Failure of the lung caused by a variety of lung
diseases leads to hypoxaemia with normocapnia or
Pneumonia Lung diseases:
Pulmonary edema (LVF) COPD (Most common)
hypocapnia. Failure of the pump results in alveolar
Pulmonary embolism Pump failure: hypoventilation and hypercapnia. Although there is
Parenchymal Lung disease Neuromuscular diseases: coexistent hypoxaemia, the hallmark of ventilatory
ARDS Guillain-Barré syndrome failure is the increase in PCO2.
Asthma (Acute exacerbation) Myasthenia gravis Both types of respiratory failure may coexist in the
same patient
Chest wall disease:
The pathophysiological mechanisms responsible for
Severe Kyphosis &/or Scoliosis
CO2 retention are not yet clear. The most attractive
Therefore in these diseases Respiratory Muscle fatigue: hypothesis for this disorder is the theory of “natural
Type 2 respiratory failure “ALL lung diseases known for wisdom”. Patients facing a load have two options,
may occur as well Type 1 Respiratory failure” either to push hard in order to maintain normal
( if these paients are severely arterial carbon dioxide and oxygen tensions at the
So, breathless- Increased work of cost of eventually becoming fatigued and exhausted
“Ty. 2 RF due to Lung dis.” breathing may lead to
DOESNOT ALWAYS mean
or to breathe at a lower minute ventilation, avoiding
respiratory mucle fatigue)
it’s COPD dyspnoea, fatigue and exhaustion but at the expense
Centre failure: of reduced alveolar ventilation. Based on most recent
Brainstem damage/ depression: work, the favoured hypothesis is that a threshold
Deep coma due to any cause inspiratory load may exist, which, when exceeded,
Overdose results in injury to the muscles and, consequently, an
CVA/Head injury/IC-SOL adaptive response is elicited to prevent and/or
Central Hypoventilation Synd. reduce this damage which in turn modulates the
pattern of breathing, however, ultimately results in
alveolar hypoventilation and CO2 retention
Treatment
Treatment of type 1 failure Treatment of type 2 failure

1.High flow oxygen 1.Controlled oxygen (in COPD)
2.Assisted ventilation: 2.Assisted ventilation:
▪Invasive (“breaths for the patient”) ▪Invasive
▪Non-invasive: (“helps the patient to breath”) ▪Non-invasive: BiPAP (Bilevel positive airway pressure)
▪ CPAP (Continuous positive airway pressure).
CPAP: machine gives a predetermined level of pressure which is equal during inspiration and expiration
BiPAP: machine delivers two levels of pressure:
 Inspiratory Positive Airway Pressure (IPAP) is a high level of pressure, applied when the patient inhales
 Expiratory Positive Airway Pressure (EPAP) is a low level of pressure exerted during exhalation
Pulmonary function test (PFT)
Although PFT will be invariably abnormal in ALMOST all lung diseases however MOST of the diseases can be
and are actually diagnosed by other means (tests other than PFT). So PFT is NOT “routinely done” in lung disease
patients.
FEV1 (Forced expiratory volume in 1 second): FEV1 is the volume exhaled during the first second of a forced expiratory
effort after a full inspiration.
FVC (Forced vital capacity): FVC is the TOTAL volume of air that can be forcibly blown out after a full inspiration.
TLC (Total lung capacity): TLC is the maximum volume of air present in the lungs.
RV (Residual volume): RV is the volume of air remaining in the lungs after a maximal exhalation.
DLCO/TLCO (Diffusing capacity/ Transfer factor of the lungs for carbon monoxide): DLCO measures the ability of the
lungs to transfer gas from inhaled air to the red blood cells of pulmonary capillaries.
KCO: Diffusion capacity of the lung per unit volume.
Basic clinical application of PFT in lung diseases
Measures airway resistance/airflow
If airflow resistance is Normal then atleast 70% of the FVC should be exhaled
in 1st second, so NORMAL FEV1/FVC > 0.7
Lung Volume study

it’s interpratation
TLC & RV
High Low
“Big Lung” “Small lung”
COPD/Emphysema Restrictive
Lung disease
Parenchymal Restrictive diseases: “small lung” so Total diffusion capacity as well capacity per unit volume- BOTH are low
Extra- Parenchymal Restrictive diseases: “small lung” but density of the lung tissue increases: so DLCO low but KCO high
Acid base balance
Normal ABG values
pH: 7.35-7.45 PO2: 80-100 mm HgPCO2: 35-40 mm Hg SpO2: 95-100%HCO3-: 22-26 mEq/L Base excess: -2 to +2
Classification of acid base disorders
Condition pH PCO2 HCO3-

(N: 7.35-7.45) (N: 35-40 mm Hg) (N: 22-26 mEq/L)
Respiratory acidosis <7.35 >40 >26
Metabolic acidosis <7.35 <35 <22
Respiratory alkalosis >7.45 <35 <22
Metabolic alkalosis >7.45 >40 >26
Steps of ABG
 Step 1: pH detection (acidosis/ alkalosis)
 Step 2: Primary process identification (respiratory/ metabolic)
 Step 3: Compensatory process identification (respiratory/ metabolic)
 Step 4: PO2 measurement
Respiratory acidosis
Condition characterized by abnormal CO2 retention
(therefore Respiratory acidosis and type 2 respiratory failure are more or less synonymous)
Causes
Pneumonia Lung diseases:
Pulmonary edema (LVF) COPD (Most common)
Pulmonary embolism Pump failure:
Parenchymal Lung disease Neuromuscular diseases: Guillain-Barré syndrome Myasthenia gravis
ARDS Chest wall disease: Severe Kyphosis &/or Scoliosis
Asthma (Acute exacerbation)
Respiratory Muscle fatigue:
“ALL lung diseases known for Type 1 Respiratory failure”
( if these paients are severely breathless- Increased work of breathing may lead to
Therefore in these diseases respiratory mucle fatigue)
Type 2 respiratory failure Centre failure:
may occur as well Brainstem damage/ depression:
Deep coma due to any cause
So, Overdose
“Ty. 2 RF due to Lung dis.” CVA/Head injury/IC-SOL
DOESNOT ALWAYS mean Central Hypoventilation Synd.
it’s COPD
Clinical features
1. Features due to high CO2 narcosis (Metabolic encephalopathy) 2. Features of underlying disease
A. Altered sensorium Because lung diseases are the commonest
B. Behaviourial disturbance cause of Resp. Acidosis so, MANY of these
C. Confusion/Convulsion/Coma patients will be breathless + hypoxic
D. Delirium
F. Flapping tremor
G. Low GCS
Investigation: To identify respiratory acidosis: ABG pH↓PCO2 ↑HCO3-↑ (fully compensated cases, pH will be normal)
Treatment: 1. Treatment of underlying disease 2. Assisted ventilation: Noninvasive/ Invasive
Metabolic acidosis
Condition characterized by excess accumulation of metabolically generated acid.
Classification and causes
Acidosis due to “Acid gain” Acidosis due to “Alkali loss”
Overproduction of H+:  Excess loss of HCO3-:
 Lactic acidosis: 1. Renal loss: Renal tubular acidosis
 Severe hypoxia: due to ANY condition 2. GI loss:
 Hypoperfusion a. Severe diarrhoea
 ANY shock: Hypovolemic/ Cardiogenic/Septic b. Internal fistulas
 3rd spacing: Acute Pancreatitis c. Uretero-sigmoidostomy
 Ketoacidosis: *Here, there is a compensatory rise of Cl- concentration:
 Diabetic ketoacidosis hyperchloremic metabolic acidosis.
 Starvation
 Alcohol intoxication
Underexcretion of H+:
 Acute kidney injury
To understand this- ref to anion gap....see below
 Chronic kidney disease
Incidentally: This group is an example of Metabolic Incidentally: This group is an example of Metabolic acidosis
acidosis with “High anion gap” with “Normal anion gap”
Clinical features For “MaMMaas”!!!.....Metabolic acidosis, you have read means you have ALSO read.............
1. Due to underlying disease Lactic acidosis/Kussmaul breathing/Anion Gap…so, NO “egulo shortnotes ele ki korbo sir”!!
2. Compensatory hyperventilation leading to rapid breathing pattern: acidotic/ Kussmaul’s breathing
Investigation: ABG: To identify metabolic acidosis (pH↓, HCO3-↓, PCO2↓) Anion gap should be calculated
Treatment: 1. Treatment of the underlying cause 2. In selective cases, when HCO3- is too low: NaHCO3 administration
Anion gap
Very Very Important for “Theroeticians”(rather “Theatricians”!!)…Hardly of any clinical importance..so, NOT for clinicians!!
Blood (serum/plasma) is electrochemically neutral so the…
SUM of the concentration of cations always equals the sum of the concentration of anions
Na +K+(unmeasured cations)= Cl+ HCO3+ (unmeasured anions)
(Na +K)- (Cl+ HCO3)= (unmeasured anions) - (unmeasured cations)
Anion gap
= defined as the difference between unmeasured cations and unmeasured anions
As Na, K, Cl, HCO3 are the principal ions, so formula TO CALCULATE AG is…..
Anion gap (AG)= (Na +K)- (Cl+ HCO3)………Normal anion gap: 3-10 mEq/L
High AG Metabolic Acidosis Normal AG Metabolic Acidosis
Acidosis due to “acid gain” Acidosis due to “alkali loss”
AG high as HCO3 falls as it gets “Overconsumed” HCO3 falls BUT more chloride is CONSERVED
To neutralize accumulated acids so (HCO3+ Cl) remains normal
So, ONLY utility of AG is to classify metabolic acidosis..(in an UNNECESSARY COMPLICATED WAY!!!)
Respiratory alkalosis
Condition characterized by excess wash out of CO2.
Primary problem: Hyperventilation
Causes
Non pathological casues Pathological casues (Pulmonary diseases)
1. Pregnancy (late stage) Pneumonia
2. Panic attack Pulmonary edema
Not Hypoxic Pulmonary embolism ALL are Hypoxic
Parenchymal Lung disease (Interstitial Lung disease)
ARDS
Acute exacerbation of asthma
Pulmonary diseases: IF SEVERE breathlessness continues EVENTUALLY respiratory muscles develop fatigue and PCO2 level will
gradually start to rise…SO “today’s Respiratory alkalosis may be tomorrow’s Resp. acidosis”
Clinical features
1. Due to the underlying disease
2. Due to hypocapnia:
 Laziness/ light headedness
 Tingling
 Perioral numbness/ paresthesia
Investigation
1. ABG: To identify respiratory alkalosis (pH↑, PCO2↓ , HCO3-↓, PO2↓)
2. Relevant investigations to assess the underlying condition.
Treatment
2. If hypoxic:
a. High flow oxygen
b. Assisted ventilation: Noninvasive/ invasive
Metabolic alkalosis
Condition characterized by excess of metabolically generated alkali (=HCO3)
Causes
1. “Relative excess” of HCO3: due to abnormal loss of H+ (actually HCl loss)
a. Severe vomiting (so, also called Hypochloremic metabolic alkalosis)
2. Overproduction of HCO3-
a. Diuretic use
b. Hypokalemia
c. Mineralocorticoid excess.
Clinical features Due to the underlying disease
Investigation
1. ABG: To identify metabolic alkalosis (pH↑, HCO3-↑, PCO2↑)
2. Investigation to assess the underlying disease
Pleural effusion
Accumulation of abnormal amount of fluid in the pleural space.
Types and causes
Typically bilateral effusion Typically Unilateral
Transudative pleural effusion Exudative pleural effusion:
LHF/ CCF Infection: 1. TB 2. “ Non TB”- Any Pyogenic organism
Quick recap!!...Systemic defect
CKD volume overload/reduced COT.. Malignancy:
CLD (with Ascites) Anasarca...if any paired areas...fluid Primary: Mesothelioma
Nephrotic syndrome accumulates bilaterally.....biochem... Pleural metastasis: Can be from any primary but
Low protein fluid (fluid comes out
without leakage of Proteins) commonly from Bronchogenic /Breast/Lymphoma
Pulm. Embolism
CLD and effusion: Ascitic fluid moves from the peritoneal Quick recap!!...Local defect...Increased
Acute Pancreatitis capillary permeability...if any paired
cavity into the pleural space (due to negative intrathoracic
Drug induced areas...fluid accumulates unilaterally
pressure) through small defects located mainly on the Right
..biochem...High protein fluid (fluid
diaphragmatic tendon. This is ALSO called hepatic comes out with leakage of Proteins)
hydrothorax- although TRANSDUDATIVE, may be
unilateral- Right sided effusion
Clinical features
Due to effusion Due to underlying etiology: (Gives clue about the cause)
Breathlessness LHF: SOB, PND, Orthopnea
Chest discomfort CLD: Abdominal swelling, GI bleeding, Encephalopathy
 Sharp pleuritic chest pain Nephrotic syndrome: Generalized swelling
(if underlying acute pleurisy) Infection: Fever, cough, dyspnea, Wt loss (TB or Pyogenic)
 dull ache in the affected side ●TB: appetite loss, Fever +/- haemoptysis (not always as
(due to weight of the fluid) Pulmonary infection is NOT a pre-requisite of Pleural infection
often ASYMTOMATIC ●Pyogenic: appetite loss, Fever

often ASYMTOMATIC!! Malignancy: weight loss, loss of appetite +/- haemoptysis
Be SYMPTOMATICor NOT….One cannot diagnose effusion (not always but may occur if Primary is Bronchogenic)
from history!!!...because even these symptoms are NOT specific Look at ……1. TB vs Pyogenic 2. TB vs Malignancy
& can occur in MANY other lung conditions Overlapping symptoms!!!
Inspection- Movement restricted Clubbing: Bronchogenic Ca
Palpation Expansion restricted. Lymphadenopathy :TB. Malignancy (Breast, Lymphoma)
Shift: To the opposite side (massive effusion) Jaundice: CLD; Metastatic liver disease
At and below the level of effusion Gallop+ Basal Crepts: LVF
Percussion: Dull Ascites: CLD/ Malignancy (malignant ascites)
Auscultation VBS↓ + VR/VF ↓ Breast examination may show the lump
Of all these diseases EFFUSION is the “mode of presentation” typically in

So effusion DOESNOT 1. Pleural Infection: TB/ Non-TB effusion But that DOESNOT mean these 2 types of
“mean” it’s a case of 2. Pleural Malignancy patients will ALWAYS present with effusion!!
TB!!!!
Therefore, after assessing a “patient of Pleural effusion”

Scenario 1 Scenario 2
Cause can be predicted Cause can NOT be predicted
Provisional diagnosis achieved No clear provisional diagnosis…BUT
MOST of the time a doctor will have differential diagnosis
Malignancy OR Infection Occult infection: TB or Non-TB organism
Occult Malignancy
Investigation
1. Blood:
 Hb/ TC/ DC/ CRP or ESR.
 Urea-creatinine Na+ K+
 LFT
2. Chest X Ray: It helps
 to diagnose effusion
 in many cases, the underlying etiology: Pneumonia/suspicious lung MASS
3. Diagnostic aspiration of pleural fluid: Often (not ALWAYS!!) diagnoses the cause of effusion
Physical character: Hemorrhagic: Malignant effusion Turbid: Infection ( Parapneumonic/TB)
Chemical character: Paired serum sample for protein and LDH:
Diagnostic criteria:
 Exudative (if it fulfils any 1 criteria):



 Transudative: doesn’t fulfil any criteria.
Microbiological character:
 Gram stain, culture sensitivity: MAY BE positive in Parapneumonic effusion
 AFB, Mycobacterial culture: MAY BE positive in TB effusion Diagnostic yield is very low
 GeneXpert TB: may be positive for M.TB DNA
Cytological character:
 Abnormal/ malignant cells: In malignant effusion ( but unable to tell the primary focus of malignancy)
 Polymorphonuclear predominant: Parapneumonic effusion
 Predominant lymphocytic: TB, Malignant effusion
Markers of TB: Adenosine Deaminase (ADA) level: high in TB effusion
4. Pleural biopsy: Either under radiological evidence/ thoracoscopically
Not a must read topic…..Optional read

Further investigation(s): OFTEN REQUIRED PARTICULARLY IF Fluid result in INCONCLUSIVE/CONCLUSIVE but
further assessment is required to “complete” the diagnosis. Nature of these tests depend on suspected diagnosis and
report of pleural fluid analysis:
Depending on the underlying etiology
Exudative fluid + LYMPHOCYTIC FLUID (but TB not confirmed):
 CECT Chest
 Pleural biopsy
Exudative fluid+ Atypical cells/malignant cells present: Tests to find out the primary focus
 CECT chest+ abdomen OR PET CT
 Biopsy of a suspicious lesion seen in CECT/PET
 Pleural biopsy
Treatment: 1. Treatment for effusion 2. Treating the underlying cause

1. Treatment for effusion:
Transudative: Usually treating the cause is sufficient to get rid of the effusion- most cases drainage is NOT required
Exudative: drainage of fluid by inserting an intercostal chest drain becomes essential under following
circumstances: 1. Symptomatic effusion 2. Moderate to Massive effusion even it is asymptomatic 3. Empyema
In case of recurrent effusion:
 Pleurodesis: adhesion is induced between visceral and parietal pleura by some sclerosing agent like Talc
 Insertion of a long term indwelling pleural catheter.
Pneumothorax
It is defined as presence of air in the pleural space.
Types:
1. Based on clinical features
Primary (in absense of lung disease)- At risk: Tall, young and thin individuals
Secondary (in presence of underlying lung disease)
At risk:
• COPD • Marfan's syndrome
• Long standing asthma • Langerhans cell histiocytosis
• TB • Lymphangioleiomyomatosis
2. Based on pathophysiology
1. Closed type: Air starts to accumulate, but the punctured area of lung gets sealed off on its own after a while.
2. Open type: Air freely flows in and out of pleura during inspiration and expiration, respectively.
3. Tension type: Here a pulmonary parenchymal flap acts as a one way valve, allowing air to move in during
inspiration but does not allowing it to come out during expiration, leading to rapidly progressing accumulation of air,
leading to compressive effect (tamponade effect) on heart and hemodynamic instability (reduced cardiac output).
Clinical features:
Symptoms
1. Dyspnea: may be mild/ severe/ rapidly progressing, depending on the amount of air in the pleural space.
2. At times, it is precipitated following a bout of severe cough.
3. Chest pain: momentary sharp chest pain may occur (due to tear of the underlying lung tissue).
4. Sudden collapse/ blackout: In tension penumothorax.
5. History suggestive of underlying lung disease may be present.
Signs
1. Tachypnea
2. Tachycardia
3. Pulse oxymetry: Low SpO2 (where normal oxygen saturation is 95-100%).
4. Cyanosis: In case of severe hypoxia
5. Hemodynamic instability: Suggestive of tension pneumothorax
Chest examination: Findings are elictible OVER the affected hemithorax

Inspection Movement: restricted
Palpation Mediastinal shifting towards the opposite side (usually in case of tension pneumothorax).
Percussion Tympanitic.
Auscultation Reduced VBS/ VR/ VF.
Added sound Pneumothorax click: A clicking sound in (left Pneumothorax) coinciding with each heart beat due to movement of pleura against the
“Final MB!!!” surface of heart Font size is deliberately kept small so that even if you want you cannot read!!
Coin percussion: A metallic sound is heard when the patient is asked to percuss a coin with another and the stetho is placed at a
diametrically opposite point.
Investigation:
1. Chest X Ray (CXR)/CT Thorax
a. Confirms diagnosis: An area of lung not traversed by bronchovascular margins. Collapsed border: Visible.
b. Presence/ absence of tracheal shifting.
2. Other relevant investigations to assess the underlying disease.
Treatment:
Persistent Air leak/Pneumo

fails to resolve
Indications of cardiothoracic referral: Cardiothoracic referral

1. Persistent air leak (bubbling> 3 days)
2. Second episode of ipsilateral pneumothorax Pleurodesis
3. First episode of contralateral pneumothorax Pleurectomy/Decortication
Post-discharge advice:
1. Avoid air travel for 4-6 weeks.
2. Refrain from deep sea diving for rest of life.
*Size of pneumothorax: Distance between rib margin and collapsed lung border at the level of hilum. If it is ≥2 cm, it is
suggestive of pneumothorax of 50% pleural space
Pneumonia
Pneumonia
Inflammation of the lung: Alveoli/Parenchyma:-
Typically by Infection= micro-organism BUT there are
Non- Infection type etiology as well…..this group is CONVENTIONALLY called Interstitial Pneumonitis/ Diffuse
Parenchymal Lung disease or Interstitial Lung disease (DPLD/ILD) (See later)
So, when we say “Pneumonia”…we mean Infection!!
Types
Setting at which Pneumonia has occurred:
1. Community acquired pneumonia 2. Hospital acquired pneumonia 3. Aspiration pneumonia
Micro-organism wise: 1.Bacterial 2. Viral (Not ONLY Covid!!..other viruses can cause pneumonia as well) 3. Fungal
Community acquired pneumonia
Pneumonia outside hospital setting/ within 48 hrs of admission in a person who hasn’t been in hospital in last 14 days.
[
Organism: May be ANY bacteria but common “Chest bacterias” are: TB is probably “the commonest” but if it’s
Strepto/H. influenza/Moraxella/Klebsiella/Mycoplasma/Legionella Tubercular pneumonia it’s called “TB hoyeche”!
Clinical features
Systemic symptoms: AND/OR Focal…Respiratory symptoms:
Fever Asymptomatic
+/- ≥ 1 of the followings OR +/- ≥ 1 of the followings
Appetite loss Breathlessness
Bodyache Chest pain: pleuritic
Chill +/-rigor Cough- Often with purulent/ mucopurulent sputum
Drowsiness Hemoptysis: blood stained sputum
Energy lack
Signs: Severity/degree of signs depend on extent/severity of Pneumonia
Altered sensorium
Breathing- rapid (tachypnoea)
Cyanosis
Decreased O2 saturation
Chest: Over the “Pneumonic zone” of chest
1. Signs of consolidation: Signs of reduced air entry:
a. Impaired percussion a.VBS: ↓ b.VR/ VF: ↓
OR
b. BBS (VR/ VF: ↑) c.crepitation:
c. crepitation
3. Pleural rub +/-
Investigation
1. Blood: 2. Sputum: Gram stain and culture-sensitivity
a. Hb, TC, DC, ESR/ CRP / Procalcitonin 3. Chest X Ray-confirms diagnosis
b. Na+ K+ Urea creatinine 4. Special tests: specially when non resolving
c. Blood C/S  CT chest
d. ABG: if the patient is hypoxic  Bronchoscopy- Bronchial wash for microbiology
Treatment
Supportive treatment (particularly if critically ill) Definitive
Airway protection: if severe hypoxia Drug: Antibiotic: Empirical therapy with:
 frequent suction (Co-amoxiclav + Macrolide) or Levofloxacin
 Intubate if required OR
Admit: if vitals unstable/not responding to oral Antibioc Severe infection= Sepsis suspected
Breathing: dpending on severity of hypoxia Pip-Taz/ 3rd or 4TH gen. Cephalosporin/ Any Carbapenem
 Oxygen (WBC count/CRP is NOT a decider of antibiotic!!!)
 Assisted ventilation: Non-invasive/ Invasive
B: Blood parameters monitoring Complications of pneumonia
B: Bed rest: till unwell 1. Septicemia
Circulation: IV fluid: if hemodynamically unstable 2. Respiratory failure
Drugs: supportive drugs 3. Lung abscess/cavity
 Antipyretic 4. Non-resolving pneumonia:
 Mucolytic agent: N-Acetylcystiene a. Wrong diagnosis
D: Diet: Nutritious diet b. Wrong choice of antibiotic
D: DVT prevention: if immobile c. Unusual/ resistant organism
Exercise: Chest Physiotherapy d. Unusal Pneumonia: ILD/DPLD
Hospital acquired pneumonia
Pneumonia occurring after 48 hours of hospital admission
Common organism: Pseudomonas, Staph. Aureus, Acinetobacter.
Clinical features and investigation: Same as community acquired pneumonia.
Treatment
Supportive treatment: Same as community acquired pneumonia.
Antimicrobial: Empirical antibiotic of choice: Piperacillin + Tazobactum Or Any Carbapenem Or Colistimethate
Aspiration pneumonia
Pneumonia secondary to aspiration of gastric content/ oropharyngeal secretion
At risk population: those with IMPAIRED SWALLOWING REFLEX

1. Impaired cough reflex-ANY Semi/unconscious pt.- 2. Neuromuscular diseases involving esophagus
eg.!!.... • Motor neurone disease
• Alcohol intoxication • Myasthemia gravis
• Brain damage • Bulbar pulsy
• Coma •
• Drug overdose (eg. sedative)
Clinical features
1. Background risk factor(s) of aspiration usually present
2. Often, sudden onset breathlessness with profuse respiratory secretion
3. Signs due to hypoxia
4. Signs of reduced air entry with crepitation.
Investigation Pneumonitic X Ray changes…OFTEN in the right lower zone
Treatment:1. Supportive treatment (as in community acquired pneumonia). 2. Antimicrobial: Co-amoxiclav or Pip-Taz
Interstitial Lung Disease (ILD)/ Intersitital Pneumonitis/DPLD
A “FAMILY” consisting of heterogenous members with a “common factor”-damage to interstitium of lung (alveolar
epithelium + capillary basement membrane). In many cases, these diseases also affect interlobular septa and ultimately
leads to Parenchymal fibrosis.( this is the “family” we referred before as “Non infection type Pneumonia”)
Types
Cryptogenic fibrosing alveolitis (Usual interstitial pneumonia/UIP)
Non-specific interstitial pneumonia (NIP)
EACH of these is an “INDEPENDENT” disease..“common factor”…
Acute interstitial pneumonia
involvement of/damages interstitium of the lung…So, let’s
Desquamative interstitial pneumonia
concentrate on “the family”
Lymphoid interstitial pneumonia
Cryptogenic organizing pneumonia
Respiratory bronchiolitis associated interstitial lung disease (RB-ILD).
Causes: 1. Idiopathic 2. Iatrogenic (Drug induced) 3. Infection 4. Immunological (Connective tissue disease).
Symptoms
Breathlessness: Onset, severity and progression depend on the underlying disease.
Chronic productive/ dry cough
Systemic: Fever/Arthralgia/Weight loss may occur
Swelling (due to Cor Pulmonale)
Signs: If breathless: Tachypnea/Low SpO2/Cyanosis
Clubbing: particularly in UIP.
Chest: Signs of reduced air entry: VBS↓, VR↓, VF↓ Crepitation: Fine inspiratory crepitation
Investigation
1. Chest X Ray: abnormal 2. CT Thorax: Charateristic appearance which is often diagnostic
3. PFT: Restrictive parenchymal defect
4. Lung biopsy If radiological appearance is inconclusive
5. Relevant investigation to diagnose any underlying disease: particularly Connective tissue disease
Treatment
1. Corticosteroid (systemic)
2. Immunosuppressive drugs:
When does one start to suspect ILD/DPLD….
a. Azathioprine
When a Pneumonia patient does not show clinico-radiological improvement
b. N-Acetyl Cysteine (NAC) even after sufficient antibiotic
c. Pirfenidone If Radiology is highly suspicious- “Atypical to be a typical Pneumonia”
3. Symptomatic:
a. Long term oxygen therapy
b. Treatment of RHF, if present.
4. Surgery: Lung transplantation.
Lung cavity
Pulmonary cavities, which are most of the time radiologically diagnosed, are gas-filled areas of the lung in the center
of a nodule, mass or area of consolidation
C: Cancer: Bronchogenic Ca: most frequently Sq.CC/ Cavitatory pulmonary metastasis
A: Autoimmune -Wegener's granulomatosis/Rheumatoid nodules
V: Vascular-Pulmonary Embolus
I: Infection (bacterial/fungal) TB/Abscess
T: Trauma – Pneumatocoele
Y: Young asymptomatic individuals- (often) pulmonary sequestration/Bronchogenic cyst
Investigations: 1. CxR 2. CECT Chest 3. Relevant others- as per suspected cause
Treatment: Treatment of the underlying causes/disease. Certain conditions do not require any treatment.
Bronchogenic Carcinoma
Malignancy of bronchial/ bronchiolar epithelium.
Risk factors: 1. Cigarette smoking: 2. Occupational exposure: Asbestos 3. Environmental toxins
 Initiator: Polyaromatic hydrocarbon
 Promoter: Phenol derivatives

Loco-regional effects Distant effects
Intrathoracic effects of bronchogenic CA Extra-thoracic effects of bronchogenic CA
1.Primary organ related manifestations 3.Metastatic: Common: Brain/L. node/Liver/bone/Serous cavities

2.Surrounding organ related manifestations 4.Non- metastatic effects (Paraneoplastic syndrome)
Intrathoracic effects Effects

Structures affected
Airway ● Obstruction ●Narrowing
Parenchyma ● Collapse ● Consolidation ● Cavitation
Pleura/ Pericardium Effusion
Ribs ●Erosion
●Irritation of intercostal nerves (ICN)
Lymph node Hilar/ mediastinal/ supraclavicular lymphadenopathy
Mediastinal structures 2 tubes: ●Esophagus ●Trachea
Compression by tumor or 2 nerves: ●Sympathetic trunk ●Recurrent laryngeal nerve
enlarged lymph nodes 2 great vessels: ●Superior vena cava ●Subclavian artery
Extra-thoracic effects Metastasis: Brain/Bone/Liver/Lymph Nodes/Serous cavities
Paraneoplastic syndromes.
Clinical features: WIDELY VARIABLE: any 1 or more than 1 of these
Symptoms:
Category Symptoms
Respiratory complaints  Breathlessness
 Productive cough
 Chest pain: dull in nature in erosion of ribs
sharp shooting in nature in irritation of IC nerves
 Hemoptysis.
Due to compression  Dysphagia
 Stridor
 Hoarseness of voice (due to injury to recurrent laryngeal nerve
 Loss of Explosive nature of cough (called ‘bovine cough’: due to RLN palsy)
 Symptoms of SVC obstruction.
Due to extrathoracic effect  Bone pain
 Liver: Jaundice
 Brain metastasis:
 Headache
 Vomiting
 Convulsion
Signs:
1. Pallor: may be present
2. Clubbing may be positive
3. Jaundice may be present (liver metastasis)
4. Signs of SVC obstruction
5. Supraclavicular lymphadenopathy
System specific signs

System Signs
Respiratory system Signs of the ANY 1 following may be present:
 Consolidation ●Cavitation ●Collapse ●Pleural effusion
GIT  Firm to hard hepatomegaly (in case of liver metastasis)

 Malignant ascites (in case of peritoneal metastasis).
CNS Following signs may be present:
 Papilledema
 Hemiparesis
 Signs due to Pancoast tumor
Paraneoplastic syndromes
Distant non-metastatic manifestations DUE TO either secretory nature of the tumor or immunologically mediated.
System involvement Symptoms
Endocrinal Hormone Effect
(most commonly seen ACTH Cushing syndrome
in small cell lung PTHrP Hypercalcemia
carcinoma) ADH SIADH
Gonadotropin Gynecomastia
CNS Lambert–Eaton myasthenic syndromeSubacute cerebellar degeneration.
Hematological DICAnemia.
CVS Non-infective endocarditisMigratory thrombophlebitis.
Renal Nephrotic/ nephritic syndrome
Investigations:
1. Suspicion: often from ABNORMAL Chest Xray
2. To confirm malignancy
3. To confirm extent/burden of the disease (“Geography”)- this is the SINGLE MOST important parameter to
STAGE the disease for ANY MALIGNANCY: 1.Loco-regional extent 2. Distant spread
4. To assess overall physical fitness of the patient: Assessment of important organs
To confirm malignancy To know the spread Overall physical assessment
Cytology/Histopathology Radioimaging (gives the 1st clue of disease) CBC
FNAC/Biopsy of Lung “mass” Contrast CT- brain+ thorax + abdomen LFT: deranged if Liver mets
1.Radiologically guided Contrast MRI- brain+ thorax + abdomen KFT: Ur/Cr
2. Bronchoscopic PET- CT whole body Na/K: Low Na: SIADH
3. At times form secondary site: Isotope bone scan- specially for Bone mets Ca: high due to
 Lymph node biopsy  Bone metastasis
 Cytology of pleural fluid  Pareneoplastic
ECG+ Echo
PFT
Treatment:
Treatment of Bronchogenic Ca

Treatment options
● Surgery and/or ● Onco-Medicine and/or ● Radiotherapy
Lobectomy Chemotherapy Targeted therapy Immunotherapy

Pneumonectomy Carboplatin Erlotinib
Cisplatin
Gemcitabine
SVC Obstruction
Occlusion of SVC due to extraluminal/ intraluminal compression.
Cause: Malignancy: Bronchogenic Ca/ Lymphoma Benign: Thymoma/ Retrosternal goiter/ SVC Clot/ thrombus.
Clinical features
Symptoms: due to venous Stasis/Congestion in the upper part of the body
1. Facial and neck swelling
2. Plethoric appearance (red, flushed) of face
3. Throbbing headache
Signs:
1. JVP: Raised and non-pulsatile
2. Facial plethora and swelling may increase on lifting both the arms (Pemberton’s sign).
3. Superficial venous prominence over the chest wall with direction of filling from above downwards may be seen.
Investigation: 1. CT Thorax 2. Histopathological confirmation the underlying disease/ condition
Treatment
1. Supportive treatment: 2. Specific treatment: Rx of the underlying cause
 Oxygen
 Steroid: to reduce the edema surrounding the obstruction.
 If the patient is in severe distress, then SVC stenting may be considered.
Pancoast tumor
Malignancy situated at the apex of the lung- may cause some unique manifestations due to it’s location-when these
manifestations occur, it is called Pancoast syndrome.
Clinical features
Cause Symptoms and signs
Compression of  Pain/ paresthesia along the ulnar border of arm and forearm
C8-T2 nerve root  Wasting of hypothenar muscles.
Compression of
Symptom Cause
Sympathetic trunk:
Miosis Due to involvement of dilator pupillae
Horner’s syndrome
Anhydrosis of same side of face Due to involvement of vasomotor fibers to face
Partial ptosis Due to paralysis of Muller’s muscle
Loss of ciliospinal reflex ---
Acute respiratory distress syndrome (ARDS)
An acute complication of VARIETIES of underlying diseases and it is characterized by non-cardiogenic pulmonary edema.
Causes: A. Acute pancreatitis R: RBC transfusion (massive) D: DIC/ Drug overdose S: Septicemia
A: Aspiration Pneumonitis
Clinical features
1. Rapidly progressing breathlessness
2. An underlying illness/ condition must be present
3. Often tachypnea/ tachycardia/ low SpO2 is present
4. Often patient is hemodynamically unstable
5. Usually bilateral crepitations are present.
Investigation:
1. ABG 3. HRCT (if pt’s condition permits)
2. Chest Xray 4. Relevant tests to assess underlying condition
Treatment
Airway protection: Often require intubation Circulation: IV fluid and vasopressors
Breathing: invasive ventilation Drugs for underlying conditions
Bronchiectasis
Abnormal, permanent dilation of bronchi/ bronchioles.
Causes
1. Infection: Post infective causes: 3. Impaired mucociliary clearance:
a. TB. a. Cystic fibrosis
b. Necrotizing pneumonia b. Primary ciliary dyskinesia
c. Whooping cough pneumonia c. Kartagener’s syndrome
2. Immune related: 4. Insult to the bronchus:
Immunodeficiency: Primary and secondary. a) Obstruction (Foreign body/ Lymph node etc.)
Hyperimmune reaction: ABPA b) Repeated gastric aspiration
c) Toxic fumes
Clinical features:
1. Chronic productive cough: often mucopurulent/ purulent; may be foul smelling. Volume and appearance of cough
suddenly changes during infective spells/ exacerbations.
2. Breathlessness.
3. Hemoptysis: It may be massive (due to rupture of bronchial artery as well as erosion of bronchial wall).
Signs:
1. Pulse oximetry: Low oxygen saturation.
2. Clubbing may be present.
3. Respiratory system: Often coarse crepitations are present, which may be diffuse/ localized depending upon the
extent of distribution of bronchiectasis.
Investigations:
Hb, TC, DC, CRP/ ESR.
Sputum: Gram stain and culture sensitivity.
Blood culture: During infective exacerbations
CXR: changes suggestive of bronchiectasis.
HRCT: Confirms the diagnosis
Treatment
Antibiotic therapy: 2 types:
 Short term (during exacerbation).
 Long term (for prophylaxis).
Bronchodilators (in case of airway obstruction).
Clearance of airway secretion (Bronchial toileting)
a. Postural drainage
b. Chest physiotherapy
c. Special breathing exercise
d. Cough assist device
Vaccine:
a. Influenza vaccine: Yearly.
b. Pneumococcal vaccine: Single dose
COPD (Chronic obstructive pulmonary disease)

It’s a chronic progressive disease characterized by fixed/irreversible airway obstruction +/- alveolar damage.
Etiology:
Cigarette smoking(10 pack Years- 50% smokers develop COPD)
Contributory factors: 1. Outdoor air pollutant 2. Occupational pollutant 3. .Indoor air pollutant (biomass fuel).
Types:
1. Chronic bronchitis: Pathologically characterized by over-secretion of bronchial mucous which manifests as chronic
productive cough lasting most of the days for at least 3 months in a year for at least 2 consecutive years.
2. Emphysema: abnormal permanent dilation of alveoli with destruction of their walls without any fibrosis.
Pathophysiological changes:
Symptoms:
Breathlessness: Chronic, slowly progressive leading to reduced exercise tolerance.
No diurnal variation/ no seasonal variation (Asthma) and no orthopnea/ PND
Chronic cough: Often productive; mucoid/ mucopurulent. May be dry also. Volume of sputum increases and becomes
more purulent during infective exacerbation.
Edema/Swelling: When RVF develops
Signs
1. Depeneding on severity of hypoxia: Tachypnea +/- Pulse oxymetry: Reduced oxygen saturation +/-Cyanosis
2. Respiratory system:
 Inspection: Hyperinflated: Barrel shaped chest.
 Palpation: No shifting.
 Percussion: Hyper-resonant at both sides.
 Auscultation: “ Signs of reduced Air Entry”- reduced VBS/ VR/ VF
 Added sounds: Rhonchi/ wheeze(due to bronchospasm).
 A localized area with crepitation may be present (due to infection of underlying parenchyma).
3. CVS: (if Cor pulmonale)
Signs of PAH: ● Accentuated P2 +/- Palpable P2 ● Mid-systolic murmur due to functional PS
Signs of RV enlargement: ● Left parasternal heave
Cor pulmonale-discussed later
Signs of RV failure: ● Raised JVP ● Bilateral edema ● Soft tender hepatomegaly.
4. Attitude: Patient sits up in a “tripod position” with outstretched hand supporting upper part of the body and
breaths with pursed lip. It is an attempt to prevent the collapsibility of the airway by increasing intra-airway pressure.
Investigation
Blood: FBC: Polycythemia (hypoxia stimulates Erythropoietin production, leading to polycythemia).
ABG: To document the baseline gas status
Sputum: Gram stain+ culture sensitivity.
Spirometry:
Pre and post-bronchodilator challenge FEV1: No evidence of reversibility.

CXR:
a. Prominent bronchovascular markings
b. Hyperinflated lung.
c. Always look for any pneumothorax.
Treatment
Principles of treatment:
A-Aviod smoking (Smoking cessation) D- Domiciliary O2 therapy
B- Breathing exercise (Pulmonary rehabilitation) E- Exacebation: Treatment of Exacerbations
C- Chest Physiotherapy E- Emerging Treatment
D-Drug (Pharmacotherapy)
Smoking cessation Nicotine replacement therapy (in different forms)- a.Nicotine patch b.Chewing gum
c. Drugs (Bupropion/ Varenicline)
Pulmonary rehabilitation 1. Special breathing techniques. 2. Cough assist device 4. Chest Physiotherapy
Pharmacotherapy
Inhalers:
Anticholinergic (anitmuscarinic) Beta 2-agonist: Corticosteroid:
Short acting: Ipratropium. Short acting: Levo-salbutamol. Fluticasone/ Budesonide
Long acting: Tiotropium Long acting: Salmeterol/ Formoterol/Indacaterol Beclomethasone
Oral:
1. Xanthine: Aminophylline/Theophylline/Acebrophylline
2. PDE-4 inhibitor: Roflumilast
3. Corticosteroid: Short term use during Exacerbation
4. Antibiotics: Short term use during Exacerbation
Vaccination: 1. Influenza vaccine: Yearly 2. Pneumococcal vaccine: Single dose + Booster after 5 years
Domiciliary long term Oxygen therapy
Criteria:
ABG: PaO2< 50 mm Hg, when done in a stable state and at least twice, at least 3 weeks apart.
ABG: PaO2: 55-60 mm Hg, with evidence of PAH/ RVF/ Polycythemia.
Duration of long term oxygen therapy: At least 15 hours a day.
Emerging Treatment: Surgery: Various options are: 1. Bullectomy 2. Lung volume reduction surgery.
Acute exacerbation of COPD
It is an acute emergency characterized by progressive worsening of COPD symptoms and commonly precipitated by
an underlying respiratory infection.
Symptoms
1. Worsening dyspnoea
2. Productive cough: Often increased in volume and more purulent in appearance (in comparison to regular sputum).
3. In some patients, symptoms of CO2 retention (CO2 Narcosis) – Encephalopathy: “abcde”
4. Systemic manifestations of infection: Appetite loss; Bodyache; Chill +/- Rigor Drowsiness/ Elevated temp
Signs Apathy Delirium
1. Hypoxic: 1.Tachypnoea +/-Tachycardia 2.Pulse oximetry: Low SpO2 3.Cyanosis
2. Hypercapnoeic: 1.Flapping tremor 2 .GCS: low/falling
3. Attitude: Patient sits up in a tripod position with outstretched hand supporting upper part of the body and breaths
pursed lip. It is an attempt to prevent the collapsibility of the airway by increasing intra-airway pressure.
4. Respiratory system 1.Signs of COPD are present 2.Widespread rhonchi and localized crepts may be present.
Investigation Same as COPD.
Treatment
Airway protection : Frequent oropharyngeal suction; Intubation if required.
Breathing: Controlled oxygen: Ideally via venturi mask PARTICULARLY IF Pco2 High. If patient is hypercapnoeic
during acute stage, a saturation of 88-92% should be acceptable, so that the hypoxia is not overcorrected.
Assisted ventilation may be required: Non-invasive (BiPAP)/ Invasive.
Circulatory support with IV fluids.
Drugs:
 Antibiotics: Oral/ IV, depending on patient’s ability to swallow a tablet and severity of infection
Usually a 7-10 days course is given.
Empirical antibiotic: Coamoxiclav + Macrolide
Severe infection/Critically ill: Carbapenem
 Aminophylline infusion: ONLY if in spite of optimum medical therapy patient remains symptomatic.
 Bronchodilator: Nebulization with Levosalbutamol + Budesonide+ Ipratropium: initial few days then inhalers
 Corticosteroid: Oral/ IV short course steroid: usually Prednisolone/ Hydrocortisone: 5- 10 days
Diet: Nutritous diet
DVT prophylaxis
Exercise: Chest Physiotherapy/Breathing exercise
Further treatment plan: appropriate long term inhalers
Bronchial asthma
It is a chronic inflammatory disease of airway characterized by reversible airway obstruction due to hyperactivity of
the airway.
Etiology
1. Underlying factors: Some of the individuals are genetically predisposed to develop airway hyper-reactivity/
inflammation spontaneously/ when exposed to external stimulus (allergen).
These individuals are called atopic- often they will have H/O recurrent allergic rhinitis/ dermatitis/ hay fever and
usually having a high serum IgE level.
2.Triggering factors: These factors quite often initiate/ precipitate an asthmatic attack. Some common substances are:
Indoor allergen: Dust/ mites/ fungus (aspergillus) Drugs: Aspirin/ β-blocker
Outdoor allergen: Dust/ smoke Physical exercise
Occupational: Isocyanate/ flour Chemical: Perfume/ tobacco smoke
Clinical features
Symptoms
1. Breathlessness:
a. May start gradually/ suddenly.
b. Often intermittent, with asymptomatic spells within 2 episodes.
c. Aggravated by exposure to allergen.
d. Shows diurnal variation: increasing symptoms at early morning as bronchial tone follows a circadian rhythm and is
maximum during these hours.
e. Often shows seasonal variation (aggravates during season changes).
2. Wheeze: Usually intermittent and occurs along with dyspnea.
3. Cough:
a. May be intermittent/ chronic.
b. Usually dry, but may be productive, characteristically thick, white sputum which becomes purulent and
increases in volume during infective exacerbations.
Sign
a. Examination may be entirely normal in asymptomatic intervals
b. During an active spell of asthma:
1. If hypoxic: Tachypnoea+ Tachycardia +/- Pulse oximetry: Low SpO2 ± Cyanosis
2. Respiratory system:
 Movement/ expansion may be restricted.
 Signs of reduced air entry: Reduced VBS, VR, VF.
 Added sound: Diffuse polyphonic wheeze may be present.
Investigation
Preliminary investigations:
1. Spirometry:
2. Bronchodilator reversibility: +Ve: Pre-bronchodilator FEV1 increases by 15%/200 ml following bronchodilator
challenge with inhaled short acting β2 agonist.
3. Chest X Ray: Often normal.
4. Blood: Hb, TC, DC, ESR/ CRP (Eosinophilia may be present)
5. Sputum: Gram stain and culture sensitivity
Special investigations:
1.Bronchial provocation test: Helpful if clinically asthma is suspected but spirometry is inconclusive. Here,
bronchoconstriction is provoked with certain substances like Methacholine/ Histamine/ Mannitol and degree of fall of
pre-bronchoconstriction FEV1 is measured.
2.Detection of allergen by skin test.
3.Examination of antibodies against common allergens (also called precipitins) in the serum.
4.Atopic/Allergic Tendency: Estimation of serum IgE.
Treatment
Principles of treatment:
A-Avoid allergens D-Drug (Pharmacotherapy)
B- Breathing exercise (Pulmonary rehabilitation) E- Exacebation: Treatment of Exacerbations
C- Chest Physiotherapy E- Emerging Treatment
Avoid allergens: If possible to avoid known triggers

Pulmonary rehabilitation 1. Special breathing techniques. 2. Cough assist device 4. Chest Physiotherapy
Pharmacotherapy
Inhalers:
Anticholinergic (anitmuscarinic) Beta 2-agonist: Corticosteroid:
Short acting: Ipratropium. Short acting: Levo-salbutamol. Fluticasone/ Budesonide
Long acting: Tiotropium Long acting: Salmeterol/ Formoterol/Indacaterol Beclomethasone
 Reliever: Short acting β2 agonist/Short acting Antimuscarinic

 Preventer: Long acting β2 agonist, Inhaler corticosteroid
Oral:
Xanthine: Aminophylline/Theophylline/Acebrophylline
Mast cell stabilizer: Sodium cromoglycate
Leukotriene antagonist: Montelukast, Zafirlukast
Corticosteroid
Anti-IgE agent: Omalizumab
[SABA/LABA: Short/long acting β2 agonist, ICS: Inhaled corticosteroid, MX:xanthine, LTA: Leukotriene antagonist
Treatment outcomes Well controlled asthma: It is defined as:
1. No symptoms (or ≤1 per week)
2. No reliever use (or ≤1 per week)
3. No nocturnal symptoms
4. No restriction of activity of daily living.
Acute exacerbation of asthma
It is an acute emergency presentation of asthma with increasing symptoms often precipitated by an underlying
infection. They are more frequent in patients with poorly controlled asthma.
Clinical features:
Symptoms:
1. Worsening dyspnea
2. Wheeze
3. Often productive cough.
Signs:
1. Depending on the severity of hypoxia: Tachypnoea +/- Low SpO2 ± Cyanosis
2. “Signs of reduced air entry”: Reduced VBS, VR, VF
3. Widespread wheeze
Investigation:
1. Blood:
 Hb, TC, DC, CRP
 ABG: Usually hypoxia with type 1 respiratory failure
 Blood culture: If patient is febrile
2. Sputum: Gram stain and culture sensitivity
3. Chest X Ray
4. ECG
Treatment:
A. Airway: Protection by frequent suction, intubation if required.
B. Breathing: High flow oxygen : target saturation ≥ 95%
Assisted ventilation: Non-invasive (CPAP)/Invasive.
C. Circulatory support by IV fluid
D.
Drugs:
Antibiotic: Short course
Aminophylline infusion: If patient remains symptomatic even after optimal medical therapy.
Bronchodilator: Nebulization with (Salbutamol + Budesonide+ Ipratropium): Initially repeated every 15-30 minutes.
When acute stage is over, it is given every 4-6 hours till the patient is stable enough to use inhaler.
Corticosteroids: Oral (Prednisolone)/ IV (Hydrocortisone) for 5-7 days.
Diet: Nutritious diet
DVT prophylaxis
E-Exercise: Chest Physiotherapy/Breathing exercise
F-Further treatment plan: appropriate long term inhalers
Points Moderate Severe Life threatening

Peak expiratory flow 50-75% 33-50% <33%
rate (% of predicted)
Features: Increasing symptoms Increasing symptoms - Silent chest
Absence of severe/ life Respiratory rate - Cyanosed
threatening features >30/min - Tachy/brady-arrhythmia
Heart rate >110/min - Hypotension
- Confusion/ coma
- pO2 <60 mm Hg
- Saturation <92%
- pCO2: Normal/ near normal.
Pulmonary thromboembolism
It is defined as occlusion of pulmonary artery/ its branches by a thrombus which usually gets dislodged from a deep
vein of lower limb. (It should be noted that venous thrombosis of upper limb is rare.)
Risk factors of PE: These are actually the risk factors of lower limb deep vein thrombosis (DVT).
Vascular stasis (COMMON) Hypercoagulable state (RARE)
Prolonged bed ridden state/ immobility • Protein C/ Protein S/ Antithrombin 3 deficiency
Lower limb fracture • Leiden's disease (Factor 5 deficiency)
Post operative state
Long haul flight
Symptoms
1. Dyspnea: Sudden onset. Severity depends on size of thrombus.
2. Pleuritic chest pain: Sudden onset. It occurs due to spread of inflammation to the adjacent pleura.
3. Hemoptysis: Small amount of hemoptysis may occur.
4. Sudden collapse: In case of a massive PE occluding pulmonary trunk/ one of the major branches of pulmonary
artery.
5. Patient may have pain and swelling in one of the lower limb (due to DVT).
6. Always look for symptoms of the underlying factor(s).
Signs
1. Tachypnea
2. Tachycardia
3. Pulse oxymetry: Low oxygen saturation.
4. Hemodynamically unstable: In case of a massive PE.
5. Lower limb examination: May show signs of DVT.
6. Respiratory system: Often normal/ unremarkable on examination.
Investigation
1. Estimation of D-Dimer: It is a fibrin degradation product (FDP) which gets released into bloodstream due to
ineffective fibrinolysis. It is a very good screening test as a negative result virtually excludes PE/DVT but a positive result
does not always confirm the diagnosis as it may also rise in other conditions
2. V/Q Scan: It shows the area of ventilation-perfusion mismatch. It may be false +Ve in pre-existing lung diseases
which can also cause V/Q mismatch.
3. CT-Pulmonary angiogram: Best test for diagnosing PE.
Associated investigations:
1. Chest X Ray.
2. ECG.
3. Echocardiogram: To assess RV dysfunction.
4. Relevant investigations: If a hypercoagulable state is suspected.
Treatment
1. Anticoagulation: Total duration of therapy: It depends on the TYPE of underlying risk factors.
Initially Injectable: Heparin (Unfractionated/ Low molecular weight/ Fondaparinux) + Oral: Warfarin/NOAC
once target INR is achieved: The target INR is 2-2.5 in case of PE/ DVT
Heparin stopped and Oral: Warfarin/NOAC is continued
2. Thrombolysis: ONLY in massive PE- Alteplase is the drug of choice.
3. In selected group of patients, insertion of IVC filter
NOACs/DOACs?
Direct oral anticoagulants (DOACs) are oral medications that specifically inhibit factors IIa or Xa. They are also known
as Novel oral anticoagulants (NOACs) or ‘Non–vitamin K antagonist’ oral anticoagulants
Drugs: Dabigatran/Rivaroxaban/Apixaban/Edoxaban
Pulmonary arterial hypertension (PAH)
It is a condition characterized by pulmonary arterial pressure >20 mm Hg.
Causes
1. Primary/Idiopathic
2. Secondary:
 Cardiac: Chronic LEFT heart diseases
 Chronic Lung disease: COPD/ILD/Bronchiectasis
 Clot: Acute or chronic Pulmonary Thromboembolic disease
 Connective tissue disease: Scleroderma/SLE/RA
Clinical features
1. Symptoms and signs of underlying disease(s)
2. Symptoms and signs due to PAH:
a. Exertional chest pain (also called right ventricular angina)
b. Shortness of breath
c. Accentuated P2 ± Palpable P2
d. MSM in case of a functional PS
e. EDM in case of a functional PR (rare).
3. Signs of RV enlargement:
a. Apical impulse shifted outwards
b. Diffuse apex impulse (in case of a RV apex)
c. Left parasternal heave
d. PSM due to a functional TR
e. Epigastric pulsation.
4. Signs of RV failure:
a. Raised JVP
b. Soft tender hepatomegaly.
Investigations
1. ECG
2. Echo: Assess RV structure/ function and an approximate estimation of pulmonary arterial pressure
3. RV catheterization
4. Relevant investigations to assess underlying disease(s).
Treatment
A. Anticoagulation agents (Significant PAH leads to a sluggish PA circulation, predisposing to formation of PA clot)
B. BP lowering agents: Calcium channel blockers: Nifedipine
PDE-5 inhibitors: Sildenafil/Tadalafil.
PG analogue: Iloprost
Endothelin receptor antagonists:Bosentan
C. Cause: Treat the underlying cause.
Cor pulmonale
It is a clinical condition characterized by right ventricular enlargement (RVE) from acute/ chronic lung pathology.
Etiology
1. Airway and Parenchymal disease: COPD/ ILD/Bronchiectasis
2. Pulmonary arterial disease: Acute or Chronic Pulmonary Thomboembolic disease
3. Thoracic cage disease: Kypho/scoliosis
Clinical features
1. Signs and symptoms of underlying disease
2. Symptoms and signs of PAH:
Symptoms: Exertional chest pain (also called Right ventricular angina).
Signs: ● Loud P2 ± Palpable P2 ● MSM due to functional PS ● EDM due to PR (occurs very lately).
3. Signs of RVE: ● Apex: Shifted outwards ● Left parasternal heave ● PSM due to a functional TR
4. Symptoms and signs of RVF:
 Symptoms: Swelling.
 Signs: a. Raised JVP b. Bilateral edema c. Soft tender hepatomegaly.
Investigation
1. To assess the underlying disease
2. To assess the RV: a. ECG b. ECHO.
Treatment
2. For RVF:
a. Salt and fluid restriction
b. Diuretics.
Short Notes!! Extrinsic allergic alveolitis/ Hypersensitivity pneumonitis
Alveolar/ parenchymal inflammation usually due to a hypersensitivity reaction against organic antigens.
Common antigens: 1.Fungus proteins 2.Bird proteins
Clinical features
1. Breathlessness: acute/ chronic
2. Dry cough
3. On examination: tachypnea, low SpO2, bilateral crepts may be found.
Investigations
Chest X Ray
1. HRCT
2. Blood: CBC
3. ABG: Hypoxic
4. Detection of serum precipitins against the organic antigens
Treatment: 1. Supportive: Oxygen: If the patient is hypoxic 2. Systemic corticosteroid
Cryptogenic organizing pneumonia
It is an atypical type of pneumonia characterized by formation of granulation tissue inside the alveoli.
Clinical features
Symptoms Signs
1. Shortness of breath 1. Tachypnea, low SpO2 ± cyanosis
2. Dry/ productive cough 2. Signs of consolidation/ reduced air entry
3. Systemic symptoms: 3. Crepitations usually present.
 Fever/Malaise/ Loss of appetite
Investigations
1. Chest X Ray:
2. HRCT: Often confirms the diagnosis
3. Lung Biopsy: In many cases, histopathological confirmation is required
4. Blood: CBC, ABG, Blood culture
5. Sputum: Gram stain and culture
Treatment
1. Supportive: Oxygen if required
2. Antibiotic: Often prevent keeping CAP (Community acquired pneumonia) in mild.
3. Corticosteroid: Many patients need prolonged course of steroids.
Sarcoidosis
It is an immunologically mediated multisystem disease characterized by non-caseating granulomatous inflammation.
Involvement and clinical features
1. Constitutional: Fever/Malaise/Arthralgia/Weight loss
2. Pulmonary: Asymptomatic
Cough: persistent dry cough; seldom productive
SOB
3. Extrapulmonaty: a. Derm: Erythema Nodosum b. CNS: 7th nerve palsy c. CVS: Arrhythmia
Investigations
1. Pulmonary:
a. Chest X Ray
b. HRCT (If CXR is abnormal) Both will show reticulonodular pattern ± lymphadenopathy.
c. Biopsy: Histopathological confirmation by biopsy from: a. Lymph node b. Parenchyma
- If radiological appearance is inconclusive.
d. Pulmonary function test: Restrictive lung disease.
2. Other investigations:
a. Hb, TC, DC, CRP/ESR
b. Liver function test
c. Serum Ca++: Hypercalcemia due to increased production of 1,25-(OH)2-cholecalciferol [vitamin D3], which causes
increased absorption of Ca++ from gut.
d. Serum Angiotensin converting enzyme (ACE):Due to release of ACE from activated macrophages. Although serum
ACE is a non-specific marker for sarcoidosis. It is an indicator of disease activity.
e. ECG: To look for conductive disturbances.
f. Biopsy of any affected organ.
Treatment: 1. Coricosteroid 2. Immunnosuppressive
Coin lesion/ Solitary pulmonary nodule

SPN, a radiological entity is defined as a well defined round or oval pulmonary parenchymal lesion ≤ 3 cm in
diameter. It is surrounded by pulmonary parenchyma and/or visceral pleura.
Coin lesion refers to a round or oval, well-circumscribed solitary pulmonary lesion. It is typically 1-5 cm in diameter
and calcification may or may not be present.Typically but not always the patient is asymptomatic
Cancer- Brochogenic Ca; Solitary Pulmonay metastasis
Artefact-Nipple shadow; cutaneous lesion-Wart/Mole
Vascular- Hamartoma/Arteriovenous malformation/Vasculitis:Wegner’s Granulomatosis
Infective/Inflammatory- ‘round’ Pneumonia/lung abscess/rheumatoid nodule
TB
Young asymptomatic individual- Congential Cysts
C/F- often asymptomatic even if it’s a pathological lesion. Manifestations, if present depend on the underlying cause-
pts may develop Cough/Sputum/SOB/Fever/Wt loss.O/E- Clubbing/Signs of Peumonia ets may be present.
Investigations
1. CxR- Nodule often gets diagnosed incidentally
2. Further tests, IF ANY depends on the suspected cause-
a. CECT: Many patients need follow up serial CTs to monitor the nodule
b. Biopsy from the lesion
c. Bronchoscopy with Bronchial wash/Bronchoalveolar lavage from the suspected lobe- for microbiological diagnosis
Treatment: 1. Malignant nodule/High risk nodules- Excision 3. Infection: Antibiotic
2. Benign/Low risk nodule- wait and watch 4. TB: ATD
Hemothorax
Blood in the pleural space.
Causes
1. Trauma- Accidental/Deliberate/ Iatrogenic- Intercostal drain/central venous catheter/ thoracostomy tube placement
(Penetrating injuries of the lungs, heart, great vessels. Blunt chest trauma can occasionally result in hemothorax by
laceration of internal vessels)
2. Nontraumatic
Neoplasia (primary or metastatic)
Bleeding disorders
Nonpulmonary intrathoracic vascular pathology-aortic aneurysm or aneurysm of the internal mammary artery
C/F-vary widely, depending on the amount and rapidity of bleeding
Chest pain
Dyspnea
Tachypnea
Diminished ipsilateral breath sounds+ dull percussion note.
If substantial blood loss has occurred- hypotension and tachycardia
Investigations
FBC/CBC
CxR
USG Chest with diagnostic fluid aspiration - hematocrit value > 50% of that of the blood hematocrit
CT Chest
Treatment: 1. Tube thoracostomy drainage/Intercostal drain 2. Video-assisted thoracoscopic surgery (VATS)
Foetid sputum
Foul smelling sputum is called foetid sputum
Causes- Usually occurs if a foci of suppurative infection in the lungs- particularly with anaerobic organism-
1. Abscess
2. Aspiration Pneumonia
3. Bacterial Pneumonia
4. Bronchiectasis
5. Cavity communicating with a major bronchus
C/F- such pts may have ≥ 1 of these manifestations
1. Productive cough- sputum- often Profuse/ often purulent/ foetid
2. Fever
3. SOB
4. Hemoptysis
5. Constitutional manifestations of infection- appetite loss/malaise/bodyache….
Investigations-
1. FBC/CRP- TC high/CRP high
2. CxR- often shows the underlying pathology
3. Sputum- G.S/C.S/ZN Stain/Myco TB
4. Blood culture
5. Special test- CT Chest/Bronchoscopyculture/XpertTB
Rx- 1. Antibiotic 2. Chest physio 3. Specific Rx, if any of underlying cause
Related SN- Purulent sputum- Exactly same, just add/modify
Purulent sputum= pus like sputum composed of white blood cells, cellular debris, dead tissue, serous fluid, and
viscous liquid (mucus).
Cause-1-5 + 6.Exacerbation COPD/Asthma 7. LRTI
Pulmonary encephalopathy
= CO2 narcosis/Hypercapnoeic respiratory failure/type 2 respiratory failure….see notes
Alpha 1 antitrypsin deficiency (AATD)

AATD is a genetic condition that predisposes to COPD and liver disease (cirrhosis and hepatocellular carcinoma)
Pathophysiology:The genetic defect (mutations) alters the configuration of the alpha1- AT molecule and prevents its
release from hepatocytes. As a result, serum level of alpha1- AT is decreased, leading to low alveolar concentrations,
where the alpha1 AT serves as protection against proteases. The resulting protease excess in alveoli destroys alveolar
walls and causes emphysema. The accumulation of excess alpha1-antitrypsin in hepatocytes leads to destruction of
these cells and ultimately, chronic liver disease.
C/F:
1. Asymptomatic till significant clinical damage occurs
2. Lung: Dyspnoea +/- cough +/-sputum production +/- wheeze: AATD pts frequently develop dyspnea many years
earlier than smokers with emphysema and normal alpha1- AT levels. By the time dyspnea becomes the dominant
manifestation and a diagnosis is established, most patients will have severe emphysema.
3. Liver: f/o cirrhosis and chronic hepatitis
Signs:
Mild emphysema generally have no abnormal findings on physical examination.
Mod- severe emphysema: ≥ 1 of the followings:
Tachypnea Young patients with “unexplained” liver disease with or without respiratory symptoms- ??AATD
Pursed-lip breathing
Hyperinflation: barrel shaped chest + increased percussion note
Decreased breath sound + wheeze
Investigations:
Definitive tests: To diagnose the condition: 1. Serum alpha1-antitrypsin level 2.Alpha1-antitrypsin phenotype
Supportive tests: To assess organ damage
Pulmonary function tests LFT
CxR USG liver
HRCT
Treatment: 1. Supportive: a. Rx of Emphysema b. Rx of Liver disease 2. Definitive: Replacing enzyme
Swine flu-management (H1NI Rx)
Antipyretics: Paracetamol
Analgesics: NSAIDs
Antiviral: Oseltamivir or Zanamivir
Indications:
1. Initial presentation with severe illness or whose condition begins to deteriorate
2. patients with underlying medical comorbidities that increase the risk of more severe disease
3. Pregnant women
4. Pre or post-exposure prophylactic antiviral for “high risk” individuals
Bedrest: if very sick
Cough suppressants
Diet: Nutritious diet
Early recognition of complication: particularly viral Pneumonia and treat it promptly if required Ventilatory support
Fluid: adequate hydration- oral fluid or if required IV fluid
Future risk prevention: Vaccine
Cardio-Vascular System
CARDIOVASCULAR
Over view of CVS
S2
S1
Heart sounds
Normal heart sounds
S1: Atrioventricular valves closure – Mitral & Tricuspid S2: Semilunar valves closure - Aortic & Pulmonary:
timing: at the end of diastole timing at the end of Systole
S3 & S4
**Genesis: You may become a cardiologist but will never become a cardio-physicist, so don’t try to “understand” in details!!
S3 (also called Ventricular gallop) S4 (also called Atrial gallop)
Genesis: Rapid filling of dilated/noncompliant/overloaded ventricle during 1st rapid filling phase (EARLY diastole) & last
rapid filling phase (Atrial systole/LATE diastole) MAY create an unusual vibratory effect- this gets transformed into a
reverberation leading to production of these sounds
Sound occurs during 1st rapid filling phase: it’s called S3 Sound occurs during last rapid filling phase: it’s called S4
EARLY diastolic (just after S2) LATE diastolic (immediately before S1)
Significance of S3 & S4: indicates Ventricular dysfunction however they DONOT appear till significant dysfunction
has occurred. So although S3 & S4 are considered to be a sign of heart failure but their absence DOESNOT rule out HF.
At times, particularly in presence of tachycardia 3 sounds together (either S1+S2+S3 or S1+S2+S4) give rise to a rhythm
resembling that of a galloping horse- this is called Gallop rhythm
Murmurs: Turbulent flow of blood strong enough to produce audible noise
Streamline flow No murmur “power” of Turbulence enough to become “audible”
So turbulent flow present- BUT murmur NOT ALWAYS audible!!

(So, any “MURMUR producing condition” can be clinically “silent”)
Murmurs
NORMAL amount of blood flowing through ABNORMAL amount of blood flowing through
an ABNORMAL orifice/opening a NORMAL orifice/opening
Organic murmur Flow/ Innocent/ functional murmur

Systolic Diastolic Systolic Diastolic
MR/TR MS/TS MR/TR MS/TS
AS/PS AR/PR AS/PS AR/PR
VSD Recapitulate cardiac cycle!!!
MR/TR: Valves close at the end of diastole MR/TR leak/gap persists from the very beginning of systole
LV/RV to LA/RA backflow from the beginning of systole and continues throughout: PAN SYSTOLIC
AR/PR: Valves close at the end of systole AR/PR leak/gap persists from the very beginning of diastole Aorta/
Pulmonary artery to LV/RV backflow from the beginning of diastole but DOESNOT continue throughout the diastole
as pressure gradient between artery & Ventricle falls with progression of diastole: so EARLY DIASTOLIC
MS/TS: Valves open during diastole In MS/TS narrowing persists from the very beginning of diastole but early
diastole is Isovolumetric Relaxation, so valves are yet to open flow through narrowed orifice starts after
Isovolumetric Relaxation period: so MID DIASTOLIC
AS/PS: Valves open during systole In AS/PS narrowing persists from the very beginning of systole but early
systole is Isovolumetric Contraction, so valves are yet to open flow through narrowed orifice starts after
Isovolumetric Contraction period: so MID SYSTOLIC
VSD: LV RV shunt continues throughout the systole & diastole but diastolic pressure gradient being
narrower, turbulence is not enough to produce audible sound: so PAN SYSTOLIC
PDA: Aorta Pulmonary artery flow through PDA continues throughout the systole & diastole with significant
turbulence: so CONTINUOUS
Neck vein
Importance: It reflects any internal abnormality in right side of heart, which may be mechanical/ electrophysiologic/
hemodynamic.
Which vein is examined? Internal jugular vein (IJV)

IJV is preferred over EJV because:
IJV is a direct branch of SVC (EJV is a not) & there are no valves in IJV (valves in EJV), so venous wave form can
propagate continuously in IJV. EJV lies in a more superficial course, so may get engorged due to peripheral factors
Clinical relevance:
1 .JVP raised or not: Raised JVP is an indicator of Right Heart pressure
2.“PURE THEORETICAL”, so NO CLINICAL IMPORTANCE!!):
Individual waveform gives an idea about certain underlying conditions- (This is “PURE THEORETICAL”!)
Difference between jugular venous wave and carotid pulsation?
Jugular venous pulse Carotid pulse
“Better seen than felt”: No definite pulsation “Better felt than seen”: Definite pulsation
Can be obliterated by pressing between two heads of SCM.
The upper border of waveform shifts with inspiration and No change
expiration.
Abdomino-jugular reflux positive. Negative
May/ may not coincide with arterial pulsation and S1 Definitely coincides
Abnormalities of JVP:
JVP raised: If venous waveform can be seen above the clavicle when the patient is semirecumbant (at an angle of 45◦)-
It can be concluded that JVP is raised as NORMALLY waveform is not visible (lies below clavicle)at this posture
Pathology Conditions
Volume overload 1. Right heart failure
2. Chronic kidney disease
Impaired venous return Constrictive pericarditis
Pericardial effusion
SVC obstruction
“PURE THEORETICAL”, so NO CLINICAL IMPORTANCE!!
Name of wave Event in the heart Pathology
a wave Right Atrial systole 1.Prominent in TS/PS/PAH
2.Gaint: Cannon A wave in AV dissociation
(Atria contracting against closed AV valve)
1.Absent: AF
c wave Transient Coning/ bulging of TV into RA at
the beginning of ventricular systole
x descent Right atrial relaXation Absent in TR
v wave Right atrial Venous filling Prominent in TR
y descent Rapid fall of RA pressure at the beginning of Rapid in TR
ventricular systole
Cyanosis
Bluish discoloration of skin and mucous membrane due to presence of abnormal quantity of deoxygenated Hb.
Amount of deoxygenated Hb required to cyanosis become evident is ≥ 5gm/dl.
Causes of cyanosis:
A. Impaired oxygen supply: Types: According to sites where it is seen:
1. High altitude Central Sites: Peripheral sites:
2. Hypoxemic respiratory condition Tongue. Finger tips
3. Right to left shunt: Buccal mucosa Tip of nose
 Intra-cardiac: Inner aspect of lips Ear lobule
 Tetralogy of Fallot Outer surface of lips
 Eisenmenger syndrome PS: this is a “finalMB type” classification!!
 Great vessels:
 Transposition of great vessels.
 PDA with reversal of shunt CYANOSIS is a sign of hypoxia BUT more important
B. Circulatory failure: Cardiogenic shock signs are….
C. Circulatory obstruction: Arterial thrombosis TACHYPNOEA… TACHYPNOEA….TACHYPNOEA!!
D. Peripheral vasoconstriction: Raynaud’s phenomenon Low O2 saturation… Low O2 saturation…!!
Differential cyanosis: It is characterized by cyanosis present in lower limb but not in upper limb. It is seen in reversal of
shunt in case of PDA, as the deoxygenated blood from the pulmonary circulation will shunt through the PDA to the
descending aorta causing the cyanosis to be seen in the lower limbs only.
Methemoglobinemia: In this condition, patient looks bluish and therefore, “looks cyanosed”.
Oedema
Collection of fluid in the subcutaneous tissue.
Causes: (for a doctor edema= pitting edema…so (s)he feels pretty pity to use “Pitting”!!!)
Bilateral Edema (SYSTEMIC DEFECT) Unilateral edema (LOCAL DEFECT)
Increased Hydrostatic pressure: Deep vein thrombosis
1. RHF Cellulitis
2. Chronic kidney disease Thrombophlebitis
3. Constrictive pericarditis Injury
4. Pericardial effusion
Decreased colloidal oncotic pressure: Concept recap….
Systemic defects: Local defect
1. Chronic liver disease
Anasarca (may be “any-sarca”) Localised edema
2. Nephrotic syndrome
Paired areas: Bilateral Paired areas: unilateral
Non-pitting edema:
Above is applicable for Superficial areas as well as deep areas
1. Lymphatic obstruction
“edema” “effusions”
2. Myxoedema
Clubbing
Loos of onychodermal angle due to proliferation of subungual
Pathophysiology:
Causes:
1. Lungs: (Respiratory disease)
a. Bronchiectasis c. Bronchogenic Ca
b. Lung abscess d. Interstitial lung disease
2. Cardiovascular disease:
a. ‘Cyanotic Heart disease’” Right to left shunt (Eg.: Tetralogy of Fallot)
b. Subacute bacterial endocarditis.
3. GIT:
a. Ulcerative colitis
b. Cirrhosis of liver
c. Primary biliary cirrhosis
4. Idiopathic
Hypertrophic osteoarthropathy (HOA)
Cause: Bronchogenic CA.
Clinical feature: In HOA, there is sub-periosteal new bone formation at the distal ends of long bones (Radius-ulna/
Tibia-fibula etc.), leading to bone pain.
Diagnosis: X-Ray.
Degrees of clubbing: (“Final MBs”!!)
1°: Fluctuating nail bed (obliteration of onycho-dermal angle)
2°: Increased antero-posterior and transverse diameter of nail bed
3°: Bulbous enlargement of pulp of the finger (Parrot beak/ drum stick appearance).
4°: Hypertrophic Osteo Arthropathy (HOA)
Acute rheumatic fever (ARF)
It is an immunologically mediated multisystem disease triggered by group A beta haemolytic streptococci.
Pathogenesis:
Group A β-hemolytic streptococci infection
Upper respiratory tract infection (Symptomatic/ Silent)…
Antibody production against streptococcus cell membrane components
Cross reaction with human tissue protein because of antigenic similarity
Acute rheumatic fever
Cardiac effects Extra-cardiac effects
Pancarditis: Arthrtits
Pericarditis: Chest pain and pericardial rub CNS: Chorea
Myocarditis: Acute heart failure Dermal
Endocarditis: Valvular endocardium involvement:  subcutaneous nodules
 Transient valvulitis: acute MS/MR/AR  Erythema marginatum
 If recurrent: Chronic valvular heart disease: Constitutional manifestations:
(MS/MR/AR/AS)  Fever\malaise
Diagnosis: Modified Jones criteria
Major criteria Minor criteria
Carditis (clinical and/or subclinical) Fever (≥38.5° F)
Arthritis (monopolyarthritis or polyarthritis, or polyarthralgia) ESR ≥30 mm and/or CRP ≥3.0 mg/dl
Chorea Prolonged PR (unless carditis is a major)
Cutaneous: subcutaneous nodules
Erythema marginatum
ARF diagnosis (initial episode): In the face of documented group A streptococcal infection 2 major criteria, or 1 major
plus 2 minor criteria may be sufficient for a presumptive diagnosis
ARF diagnosis (subsequent episode): With a reliable past history of ARF or established RHD, and in the face of
documented group A streptococcal infection, 2 major or 1 major + 2 minor, or 3 minor manifestations may be
sufficient for a presumptive diagnosis
Investigation
1. Complete blood count, CRP/ ESR 3. Echocardiogram
2. ECG. 4. ASO titre/Anti hyaluronidase/ Anti DNAase
Treatment
Treatment of “current” episode:
Anti-inflammatory:
1. Aspirin: For rheumatic polyarthritis which dramatically responses to aspirin
2. Corticosteroids: MUST be used if any Rheumatic carditis (clinically evident and/or Echocardiogarphic evidence)
Antipyretic: Paracetamol
Future risk prevention: Prophylaxis against recurrent streptococcal infection
Antibiotics: Benzyl penicillin IM 1.2 million units every 3 weeks.
 Duration of prophylactic therapy:
Duration of the prophylaxis depends on initial presentation of the patient:
 Carditis in any form: Lifelong prophylaxis.
 No carditis: For the next 5 years/ Till the patient reaches 25 years of age (whichever is later)
Infective Endocarditis
It is defined as the infection of cardiac valves and mural endocardium.
Microbiology/ Etiology:
1. According to progression 1. Acute: Commonly by Staph.aureus 2. Subacute: Strep.viridans/ HACEK group
2. According to valve involved
Natural/Native valve endocarditis: Strep.viridans/ Staph.aureus in IV drug abusers
Prosthetic valve endocarditis
 Early onset: Within 2 months: Staph.aureus
 Late onset: After 2 months: Strep.viridans
Pathophysiology with clinical manifestations:
At risk population: Pre-existing valvular disease, Congenital heart disease, Prosthetic heart valve.
Bacteremia: Natural infection/From high risk procedures/IV drug abusers

Endocarditis: Vegetation (Mass of micro-organism + platelet+ fibrin)
Cardiac and extra-cardiac effects

Clinical manifestations: ≥ 1 of the following 3 groups
1. Cardiac effects:
 Worsening of pre-existing valvular damage / new damage: Change in the quality/ intensity of a pre-existing
murmur or appearance of a new murmur [usually a regurgitant murmur].
 Formation of myocardial abscess, resulting in conduction abnormality
2. Extra-cardiac effects: ≥ 1 of the following
Embolic manifestations:
 Involvement of CNS:
 Transient ischemic attacks (TIA)
 Brain abscess
 Involvement of kidney: Acute loin pain.
 Involvement of spleen:
 Acute left upper quadrant pain due to splenic infarction.
 Splenic rub is found if splenic capsule is involved.
 Involvement of digital arteries:
 Sub-ungual/ splinter hemorrhage (linear streaks of hemorrhage best seen in nail bed)
 Janeway lesion (small hemorrhagic spots seen on palm and sole).
Effects due to immune complex deposition:
 In kidney: Acute glomerulonephritis
 In joints: Arthritis
 Retina: Roth spots (Retinal hemorrhages typically observed by an ophthalmoscope).
3.Constitutional manifestations: fever, malaise, appetite loss
Investigation
1. Complete blood count: Hb, TC, DC, ESR/CRP
2. ECG: To rule out any conduction abnormality.
3. CXR: May show cardiomegaly due to pre-existing valvular disease.
4. Echo-cardiogram:
a. Conventional/ Trans thoracic Echo: May/ may not show vegetations as they are usually deep-seated.
b. Trans-oesophageal Echo: It is the best modality and the gold standard of diagnosis of a case of IE.
5. Blood culture:The blood culture samples should be taken before the first dose of antibiotic. At least 2 sets of sample
should taken from 2 different sites.
Treatment
1. An empirical regimen (IV Ceftriaxone + Gentamicin+ IV Vancomycin) is usually administered before the result of
blood culture comes. This regimen may further be modified according to the culture-sensitivity result. Therapy should
be continued for at least 4-6 weeks duration.
2. Symptomatic treatment of underlying valvular heart disease/ complication should be given concurrently.
3. Prophylactic antibiotic should be given to all patients who are at high risk of developing endocarditis: valvular
heart disease/ congenital heart disease/ prosthetic heart valve)
 Before undertaking certain types of invasive procedures, which can potentially cause Staph/Strep.
Bacteraemia like orodental/ respiratory tract/ skin and soft tissue procedures
A single prophylactic dose of Ampicillin/ Amoxicillin/ Clindamycin should be administered just before the procedure.
Heart failure
It is a condition where heart is unable to pump blood at an amount commensurate with the metabolic needs of the
tissue (in spite of a normal venous return).
Congestive cardiac failure (CCF): Cardiac failure with congestion behind the chamber that has failed.
In case of LHF, there is pulmonary congestion (congestion behind the LA).
In case of RHF, there is systemic congestion (congestion behind the RA).
Types:
1. On the basis of onset: 1. Acute HF 2. Chronic HF
2. On the basis of chamber affected: 1. LHF 2. RHF
3. According to ejection fraction: HF is of 2 types
a. Preserved ejection fraction (HF with p-EF): Also referred to as diastolic heart failure. The heart muscle
contracts normally but the ventricles do not relax as they should during ventricular filling.
b. Reduced ejection fraction (HF with r-EF): Also referred to as systolic heart failure. The heart muscle does not
contract effectively and less oxygen-rich blood is pumped out to the body.
4. On the basis of mechanism of clinical manifestation:
a. Forward failure (features of suboptimal CO, less prominent).
b. Backward failure (congestive features, more prominent).
5. On the basis of cardiac output:
a. Low output failure.
b. High output failure (Ex.: anemia/ thyrotoxicosis/ pregnancy).
Ejection fraction
By the time diastole ends, each ventricle has filled up with blood. This amount of blood is the end diastolic volume or
EDV. The amount of blood ejected during the systole is the stroke volume. At the end of systole the volume of blood
remaining in each ventricle is the end systolic volume or. So, SV = EDV- ESV
Ejection fraction is that fraction/ % of End diastolic volume that the ventricle ejects. Normally it’s 55-70
Aggravating/Exacerbating factors:
A: Anaemia Bacteremia: Severe Infection
A: Arrhythmia C: Coronary artery event
BP: Accelerated Hypertension D: Dietary or drug non compliance
Causes of heart failure:
LHF
RHF
1. Systemic hypertension 1. Long standing PAH due to ANY of the following causes
2. Valvular heart disease: Mitral or Aortic valve  Chronic Left HF
3. Cardiomyopathy  Chronic lung disease: COPD/ Bronchiectasis/ ILD
4. Ischemic heart disease  Clot: Acute/ chronic PTE
5. Myocarditis  Connective tissue disease: Scleroderma
 Primary/ idiopathic PAH
2. Congenital heart disease
3. Valvular heart disease: Pulmonay/Tricuspid Valve dis.
4. Cardiomyopathy
5. IHD
6. Myocarditis
Signs and symptoms of heart failure
LHF RHF
Symptoms: Symptoms:
 Due to pulmonary congestion (“backward effect”)  Swelling of the body usually starts in the lower limb.
1. Breathlessness  Due to underlying etiology
2. Orthopnoea absence of Orthopnoea or PND DOES o Symptoms of LHF
3. PND NOT rule out LHF o Symptoms of underlying chronic lung disease
4. Cough: with postural and Nocturnal worsening (As LHF and Chronic lung diseases are 2 MOST
 Due to low cardiac output: (“forward effect”) COMMMON causes of RHF so these RHF patients are
1. Exercise tolerance poor OFTEN breathless)
2. Fatigue
Due to underlying etiology
Signs:  Raised JVP.
 Gallop rhythm (S3/S4).  Bilateral edema.
 Bibasal fine respiratory crepitation  Soft tender hepatomegaly.
 Signs due to LHF/ Chronic Lung Disease/ any other
etiology
Investigations
1. Hb/ TC/ DC/ ESR or CRP: Anemia is an aggravating factor of HF
2. Urea, Creatinine Na+ K+: should be monitored regularly
3. LFT: Non-specifically deranged due to congestive hepatitis.
4. Arterial blood gas: It is used to assess the degree of hypoxia in LHF
5. Pro BNP (Brain natriuretic peptide)/ N terminal pro BNP: Usually elevated if ventricular filling pressure rises,
which invariably occurs in HF. However, it is also raised in presence of LV dilation/ stretching/ significant stress.
6. ECG: May show evidence of underlying etiology/ complication(s)/ chamber enlargement.
7. CXR: Helpful in diagnosing:
a. Acute pulmonary edema
b. Cardiomegaly
8. Echocardiogram: shows Any systolic/ diastolic dysfunction/ Degree of dysfunction/ Any structural abnormality.
9. Other relevant investigations must be done to diagnose the etiology/ cardiovascular risk factors.
Treatment of HF
1. Treatment of HF 2. Treatment of etiology 3. Treatment of any aggravating/ exacerbating factor(s)
Treatment of acute LVF
Airway: If not patent, (suction +/ intubation) is indicated.
Breathing:
 Moist oxygen inhalation.
 Assisted ventilation: Non-invasive/ invasive
Basic investigation: CBC/ U&Es/ ABG/BNP/ CxR/ Echo
Circulation: IV infusion of Dobutamine/ Milrinone: In case of cardiogenic shock (contractility enhancing
drugs:inotropes (Milrinone is a phosphodiesterase 3 inhibitor with inotropic and vasodilator properties, so“inodilator”)
Drugs:
1. Diuretics (Furosemide/ Torsemide/ Bumetanide
2. Dilators:There are 2 types of dilators used in treatment of acute LVF:
a. Venodilators: Decreases preload: IV Nitroglycerine infusion.
b. Arteriolar dilator: Decreases afterload: Nitroprusside, Nesiritide (a recombinant BNP stimulating
cGMP, resulting in cardiac smooth muscle relaxation)
Diet: Salt and fluid restriction
Daily monitoring of fluid intake and output
Etiological treatment
Treatment of chronic heart failure
Drugs:≥ 1 of the following drugs depending on the clinical condition/ type of heart failure
3. ARANI: Valsartan/Sacubitril
5. β-blocker: Metoprolol/ Carvedilol (α+β1 blocker)/Bisoprolol
They should be started cautiously at a low dose and then uptitrated gradually.
6. Contractility enhancing agent: Digoxin- Limited role: In severe systolic dysfunction with coexisting A. fibrillation.
7. Diuretics: Furosemide/Torsemide/ Bumetanide.
8. Dilator: Vasodilators: Newer drug in Heart failure…the
 Venodilator: Reduces preload: Oral nitroglycerine/ GTN. group is called “ARANI”:
 Arteriolar dilator: Reduces afterload: Hydralazine.
Angiotensin Receptor
Antagonist/Neprilysin Inhibitors.
Diet: Salt and fluid restriction.
The combined angiotensin receptor
E: Etiologic treatment.
antagonist/neprilysin inhibitor was
E: Treatment of exacerbating factors developed to address two
External interventions: pathophysiological mechanisms
 Implantation of biventricular pacemaker (Resynchronization) underlying heart failure – activation
 Implantation of implantable defibrillator of the renin-angiotensin aldosterone
E: End stage Heart failure: Cardiac transplantation system (RAAS) and decreased
Treatment of RHF sensitivity to natriuretic peptides.
1. Diuretics. eg: Valsartan/Sacubitril
2. Dietary salt and fluid restriction
3. Monitoring of volume status:
 Regular body weight estimation.
 Monitoring of fluid intake and output.
 Regular monitoring of renal function (Urea-creatinine Na+ K+).
4. Treatment of LHF, if present.
5. Treatment of chronic lung disease, if present.
6. Treatment of underlying etiology.
Arrhythmia
Tachyarrhythmia Bradyarrhythmia
Sinus arrhythmia SA nodal disease

● Sinus Tachycardia ● Sinus bradycardia
Atrial tachycardia ● Sick sinus syndrome
● Multifocal atrial tachycardia Heart blocks/ AV block
● Supraventricular tachycardia (SVT) ● First degree heart block
● Atrial fibrillation (Afib) ● Second degree heart block
● Atrial flutter ●Third degree/ Complete heart block
Atrial + Junctional= Supraventricular
Junctional arrhythmias
● AV nodal reentrant tachycardia
● Junctional tachycardia
Ventricular arrhythmia
● Premature ventricular contractions (PVCs) also called ventricular extra beats (VEBs)
● Accelerated idioventricular rhythm
● Ventricular tachycardia
● Ventricular fibrillation
Tachyarrhythmia
Etiology
Chamber enlargement: due to VARIETIES of structural hear disease-
 Cardiomyopathy
 Congenital diseases
Coronary artery disease
 Chronic or Acute Ischaemic injury
Drugs: Sympathomimetics
Electrolyte imbalance: Hypo/Hyperkalemia; Hypomagnesemia; Hypocalcemia
Endocrinopathy: Thyrotoxicosis/Pheochromocytoma
Atrial fibrillation
Etiology:
Alternative way of classifying causes:
Alcohol abuse
1. Valvular cause of AF: AF associated with Mitral Valve disease (MS/MR)
Bacteremia: sepsis
2. Non Valvular causes: Rest of them
Chamber enlargement: due to VARIETIES of structural hear disease-

 Cardiomyopathy
 Congenital diseases
 Chronic or Acute Ischaemic injury
Chronic heart failure
COPD
Drugs: Sympathomimetics
Endocrinopathy: Thyrotoxicosis/Pheochromocytoma
“E”diopathic: also known as Lone Atrial Fibrillation
1. Patient typically < 60 years 2. No precipitating cause identified
Bradyarrhythmia
Causes:
Age related degeneration of conduction pathway
Birth defect: Congenital heart diseases of Conduction system
 Chronic or Acute Ischaemic injury (by causing ischaemic injury to conduction pathway)
Drugs: Rate limiting drugs: Betablockers/ Digoxin/ CCBs ( Diltiazem/Verapamil)
Endocrinopathy: Hypothyroidism
Significance/Implication of arrhythmias
1. Tachy or Brady- BOTH if/ when SIGNIFICANTLY accelerates/slows down heart rate can compromise EFFECTIVE
cardiac output…
a. when arrhythmia is TRANSIENT & self limiting this leads to SYNCOPE
b. but if arrhythmia is PERSISTENT this can lead to CARDIAC ARREST!!
2. Tachyarrhythmia can increase cardiac work load so MAY PRECIPITATE/ AGGRAVATE acute heart failure
particularly if it’s already a compromised heart
2. Special significance of AF ( in addition to above 2): predisposes to LA stagnation LA clot formation

Dislodgement of the clot Embolic event (MOST IMPORTANT consequence Embolic stroke)
C/F (of BOTH)

Asymptomatic
Black-out (syncope)
Chest discomfort
Cardiac arrest
Death
Dizziness
Etiology related symptoms
“Fainting” like sensation
Galloping (palpitation)
Signs:
1.Rate: Tahcy/ brady
2.BP: stable/unstable
Investigations: (of BOTH)

Electrolyte: K/Ca/Mg
Endocrine: TSH
ECG
24 hours ECG (Holter)
Echocardiography
Etiology related investigations
Treatment
Tachyarrhythmia Treat the underlying cause, if any: often treating the

cause is enough to abort/terminate arrhythmia
Not all need treatment, if treatment indicated 1 DECIDING factor is
Hemodynamically unstable Hemodynamically stable

Urgent cardioversion
Supraventricular Ventricular Supraventricular Ventricular
Electrical cardioversion Electrical cardioversion Amiodarone Amiodarone

Pharmacological cardioversion Beta blocker Beta blocker
Adenosine CCB
Amiodarone Digoxin
Elective electrical cardioversion
Flecainide
Atrial fibrillation: Treat the underlying cause, if any: at times

treating the cause is enough to abort/terminate AF
2 important strategy
Antiarrhythmic Rx Anticoagulation
Not all need treatment, if treatment indicated 1 DECIDING factor is Depending on CHADSVAsc score
some will be eligible
Hemodynamically unstable Hemodynamically stable for anticoagultion
Electrical cardioversion Rhythm conversion 1.Warfarin
Pharmacological cardioversion Pharmacological 2.Non VKA
Amiodarone Amiodarone Dabigatran
Flecainide Rivaroxaban
Elective electrical cardioversion
Rate control
Beta blocker
CCB
Digoxin
Rhythm conversion/Cardioversion: To convert the rhythm in to sinus rhythm (atrial & ventricular activity goes back
under SA node)
Rate control: Atrial activity remains CHAOTIC (AF continues) but VENTRICULAR rate is slowed down
Bradyarrhythmia Treat the underlying cause, if any: often treating the

cause is enough to abort/terminate arrhythmia
Not all need treatment, if treatment usually indicated in
All third degree + High risk 2nd degree
Hemodynamically unstable Hemodynamically stable
Temporary Pacemaker insertion permanent pacemaker insertion

once stable permanent pacemaker insertion
Ischemic Heart Disease (IHD)
Spectrum of IHD:
1. Minor Coronary Artery Disease(CAD): Asymptomatic patients of IHD
2. Stable angina: “stable” CAD- atherosclerotic luminal narrowing but no thrombotic occlusion
3. Acute coronary syndrome (ACS): ACS refers to an “umbrella term” for situations where the blood supplied to the
heart is suddenly blocked. It is almost always associated with rupture of an atherosclerotic plaque and partial or
complete thrombosis of a coronary artery.
Consequence of occlusion
1. Myocardial Infarction 2.Non MI ACS/Unstable angina

• STEMI
• Non- STEMI
Etiology of IHD:
Coronary artery atherosclerotic disease (CAD) Non atherosclerotic coronary artery disease (RARE!!)
Risk factors: Coronary vasculitis: Arteritis
A: Abdominal Obesity Coronary vasospasm (Prinzmetal angina).
B: BP
C: Cigarette
D: Diabetes
D: Dyslipidemia
E: Exercise lack
Less important ones are: F: Family History positive G: Gender (Male> Female) H: Hyperhomocysteinemia
There are also some precipitating factors which usually come into play only in the presence of CAD. They may
precipitate an ischemic event either acutely or chronically either by increasing myocardial work load or by increasing
the myocardial oxygen demand.
Activity: Aortic stenosis (or any other condition associated with
 Physical exertion significant LVH)
 Emotional stress Accelerated Hypertension
Anaemia Abnormal Thyroid: Thyrotoxicosis
Arrhythmia
Stable Angina/ Angina Pectoris
Stable angina is defined as a relative coronary insufficiency particularly when myocardial oxygen demand increases.
Symptoms:
Chest pain:
Site: Precordial/ retrosternal.
Nature: More a discomfort rather than a pain. Common expression used by the patients:
● Tightness/ heaviness of chest ● Sense of indigestion
Duration: Usually doesn’t last more than 15-20 minutes and resolves within 3-4 minutes.
Aggravating factor:
● Physical exertion
● Emotional excitement/stress but any factor that increases myocardial oxygen demand can precipitate angina in a
patient with CAAD)
Relieving factor:
● Avoidance/ cessation of the aggravating factor(s) ● Usually rapid relief with short & rapid acting nitrates.
Radiation: Neck/ jaw/ left shoulder/ inner aspect of left upper limb, occasionally pain may even start at these areas.
Localization: Anginal pain is NEVER sharply localized.
Signs: Cardiac examination may be absolutely normal but thorough assessment should be done for any evidence of
risk factors of atherosclerosis.
Investigations:
Aims:
a. To establish the diagnosis b. Cardiovascular risk stratification
To establish the diagnosis of IHD: 1. Lipid profile
1. ECG: May be normal/ may show ischemic changes: ST-T changes 2. Glycemic profile
2. Enzymes: Trop T/I + CK-MB: Normal in stable angina
3. Echocardiography: To look for any regional wall motion abnormality(RWMA)
4. Exercise test (Provocable Ischaemia): Ischaemia is provoked by putting the heart under stress (which increases
oxygen demand) and any ischaemia is captured by an objective mean/parameter.
Test Ischemia provoked by Ischaemia captured by
1.Exercise Tolerance Test (ETT)/ Continuous physical continuous ECG for any ischaemic changes
Treadmill test (TMT exercise
2. Myocardial perfusion scan Myocardial imaging for any perfusion defect
Physical stress
Physical exercise/Adenosine
Pharmacological stress
administration
3.Dobutamine Stress Echo Dobutamine administration Echo: for any wall motion abnormality
5. Evaluation of Coronary artery : Visualization of coronary artery:

a. CT coronary Angio (Non- invasive test)
b. Coronary Angiogram(Invasive test)
Treatment:
Strategies and their aims:
1. Risk factor modification: to prevent future risk of Ischemic event
2. Antianginal treatment: To optimize Coronary blood flow and keep painfree
3. Revascularisation/Reperfusion therapy: to re-establish a normal coronary flow
1. Risk factor modification: BOTH equally important: 1. Lifestyle modification 2. Pharmacotherapy

 Abdominal obesity: Regular exercise
 Blood pressure: Dietary modification + Antihypertensive TREATMENT: Alternative format
 Cigarette: Quit smoking NON pharmacological: Lifestyle modification
 Dyslipidemia: Dietary modification + “Statin” Pharmacological:
 Diabetes: Dietary modification + Antidiabetic Antiplatelet Antihypertensive
 Exercise lack: Regular physical exercise Antianginal +/- Antidiabetic
 Future Thrombosis prevention: Antiplatelet drug: Aspirin Betablocker “Anti”cholesterol
2. Antianginal treatment Interventional: PCI with senting/CABG

Antianginal: (Coronary vasodilator)
 Nitrate/ Nitroglycerine
 Ranolazine
≥ 1 of these Antianginal depending on clinical response
 Nicorandil
 Amlodipine or Diltiazem (weak antianginal)
β-blocker: Metoprolol/ Carvedilol/ Bisoprolol (by reducing Myocardial work load/oxygen demand they INDIRECTLY
play the role of an antianginal)
4. Interventional treatment: Revacularisation technique: 2 types:

1. Percutaneous coronary intervention (PCI): Stenting
2. Coronary artery bypass grafting (CABG)
ACUTE CORONARY SYNDROME (ACS)
It is an acute, unstable, cardiac ischemic state with/ without myocardial damage due to acute thrombotic occlusion of
coronary artery.
Types:
1. ACS with myocardial cell death: MI ACS without MI: Non MI ACS/ Unstable angina
 STEMI
 NSTEMI
Pathophysiology:
Acute Coronary Syndrome (MI or Non MI ACS)
Not always= NOT EVERYBODY become complicated
Uncomplicated Complicated
Pump failure
• Acute LVF
Ischaemic • Acute RVF
• pain +/- Arrhythmia
• Bradyarrhythmia
• Tachyarrhythmia
Myocardial rupture
• Cardiac tamponade (due to blood accumulating in pericardium)
• VSD
• MR (due to papillary muscle rupture)
Symptoms:
Chest pain:
 Site: Retrosternal.
 Character: A discomfort rather than a pain
 Expressions used by the patient:
 Heaviness/ tightness of chest
 Sense of indigestion
 Duration: Usually last for more than 15-20 minutes.
 Precipitating factor: Nothing specific however ACS may occur during physical exertion / emotional excitement
 Relieving factor: Pain usually DOES NOT subside with cessation of activity/ rapid acting nitrate.
 Radiation: Neck/ jaw/ left shoulder/ inner aspect of left upper limb.
 Localization: Pain is usually not sharply localized.
Accompanying symptoms:
 Severe sweating (due to sympathetic overactivity)
 Few episodes of involuntary defecation/ vomiting (usually a feature of inferior wall MI, due to parasympathetic
overactivity as vagus nerve is situated near the inferior wall of heart, so features of vagal stimulation are usually seen).
Associated symptoms: These are symptoms of complications & ≥1 of the followings MAY BE present
 Acute shortness of breath (due to Acute LVF)
 Palpitation/ syncope (due to arrhythmia)
 Sudden collapse/ sudden death (due to fatal arrhythmia/ severe cardiogenic shock)
Signs: ≥ 1 MAY BE present
1. Signs of acute LVF: Gallop rhythm (S3/S4), Bibasal crepts
2. Signs of acute RVF: Raised JVP, Hemodynamic instability
3. Signs acute cardiogenic shock: Low pulse, low BP
4. Signs of acute MR/ acute VSD: A pansystolic murmur
5. Signs of tachy/ brady-arrhythmia.
Investigation:
1.To establish AMI and its immediate complications, the following investigations are to be done:
1. ECG:
STEMI: NSTEMI/ Non MI ACS:
ST elevation. ST depression.
Abnormal Q wave T inversion (T↓).
T inversion (T↓).
Reciprocal ST depression
In all patients with suspected MI, serial ECG every 15-30 minutes must be done, particularly during first 2 hours post
admission – to look for any dynamic ECG changes suggestive of ongoing ischemic event
2. Enzymes: (Cardiac biomarkers)
1. Cardiospecific: 2. Non cardiospecific markers:
 Trop-T/ Trop-I  LDH
 CK-MB  Total CPK
 AST
Cardiac markers are often sent serially at an interval of 6- 8 hours during first 24-48 hours to see the trend
Time taken for serum level to rise and to normalize
Markers Time of elevation Time of normalization
Trop-T/Trop-I 6 hours 7-10 days; upto 14 days
CK-MB 8 hours 72 hours
3.Echocardiogram: It’s one of the most sensitive tests to diagnose AMI. It can potentially show:
a. Regional wall motion abnormality(RWMA)/ akinetic wall
b. Degree of cardiac dysfunction.
c. Acute MR/ VSD/ Tamponade.
4.Evaluation of coronary artery: Coronary angiogram.
2.Risk stratification + Overall assessment of patient
1. CBC
2. Urea/Creatinine/Na+/K+
3. Lipid profile
4. FBG & PPBGand postprandial blood sugar
Treatment:
1. Life style modification: for Risk factor modification
2. Medical Management: for
 Risk factor modification
 Prevention of future thrombotic event
 Cardioprotective effect
 Complication
3. Reperfusion/ revacularisation: To re-establish blood flow to the blocked artery
a. PCI is the acute stabilization method of choice for patients with on going ischemia and acute MI
b. CABG continues to be the complete revascularization option for patients with multivessel, multi-lesion CAD,
diabetes.
Initial management
STEMI within 12 hrs

of symptoms onset:
“Golden period”:
first 90 mins
Yes but not feasible
>2 mm of STE in 2 contiguo

contiguous leads or ongoin
Ongoing chest pain with
new LBBB within 3 hours of
onset of chest pain
Long term treatment:

Risk factor modification: 1. Lifestyle modification 2. Pharmacotherapy
Abdominal obesity: Regular exercise
Blood pressure: Antihypertensive
Cigarette: Quit smoking
Dyslipidemia: Dietary modificaiton
Diabetes: Dietary modification
Exercise lack: Regular physical exercise
Medical management:
Prevention of future thrombotic event
1. Antiplatelet:
 Aspirin: Lifelong.
 Clopidogrel/ Prasugrel/ Ticagrelor: to be continued for 12 months after stenting (upto 24 months).
2. Anticoagulant: for 5-7 days post MI or post Unstable angina
 Low molecular weight heparin (LMW-Heparin)
 Fondaparinux
Cardioprotective effect
1. ACE inhibitor/ ARB
2. Anti-anginal agents: Nitrate/ Nicorandil/ Ranolazine
3. Beta blocker: Metoprolol/ Bisoprolol/ Carvedilol.
4. CCB: Very limited role in MI. If at all to be used, then following are used:
a. Amlodipine.
b. Diltiazem.
Risk factor modification:
1. Atorvastatin/ any other statins
2. Antihypertensive
3. Antidiabetic
Thrombolysis in MI
Indications: IN STEMI when Primary PCI is not feasible but there is
1. >2 mm of ST segment elevation in 2 inferior leads/ at least 2 contiguous precordial leads
2. Ongoing chest pain with new onset left bundle branch block (LBBB)
Thrombolysis is indicated if the above ECG changes are present in a patient with ongoing chest pain if the patient
presents within 3 hours of onset of chest pain. After this period, effectiveness of thrombolysis progressively declines;
however the period can be stretched maximum upto 12 hours.
Drugs used:
1. Recombinant tissue plasminogen activator (Recombinant tPA): Alteplase/Reteplase/Tenecteplase
2. Streptokinase
Contraindication:
1. H/O intracerebral hemorrhage
2. H/O recent ischemic stroke
3. Known case of intracerebral space occupying lesion (SOL)
4. Any active bleeding (excluding menstruation)
Complication:Minor/ severe bleeding manifestations.
Criteria of successful thrombolysis:
1. Significant relief of chest pain
2. 90 minutes post-thrombolysis ECG shows at least 50% resolution of ST elevation.
Complications of MI
Immediate/ early (within few days):
a. Acute cardiogenic shock. d. Acute MR/ Acute VSD
b. Acute heart failure (RHF/ LHF) e. Acute cardiac tamponade
c. Arrhythmia f. Acute pericarditis
Delayed (after few weeks):Dressler’s syndrome: secondary form of pericarditis that occurs typically 2-3 weeks after
an episode of MI due to an autoimmune reaction against the leaked myocardial proteins
a. Aneurysmal dilation of ventricular wall, which may lead to systemic embolism.
Pericardial diseases
Acute pericarditis
Acute inflammation of the pericardium
Etiology:
Idiopathic pericarditis  Chest trauma
Infectious pericarditis: Irradiation
 Viral Immune:
 Tuberculosis  Collagen-vascular diseases
 Pyogenic Bacteria  Post CABG
Injury  Postmyocardial infarction pericarditis
 Organ: AKI/CKD
Symptoms: Rapid-onset chest pain located precordial and retrosternal region, and radiating to the subclavian region,
the back and the trapezoid region. Chest pain is of moderate severity and increases with inspiration or chest
movement. Patients typically alleviate the pain by sitting and leaning forward.
Signs: Pericardial friction rub is pathognomonic of pericarditis

Investigation:
1. ECG changes are frequently present: diffuse concave (“scooped”) ST-elevation in several leads.
2. Chest X-ray: To look for Pericardial effusion which may appear following pericarditis
3. Echocardiography To look for Pericardial effusion
Although initial presentation may mimic STEMI, Onset of chest pain is less abrupt in acute pericarditis, and varies
with respiration. Furthermore, diffuse ST-segment changes are present in pericarditis, whereas STEMI presents with
ST-segment elevation in leads corresponding to the ischemic myocardium. Biomarkers can be positive in both
syndromes.
Treatment:
1. NSAID: Aspirin (or any other)
2. Corticosteroids should, however, be avoided as they are associated with relapsing pericarditis.
3. Hospital admission may be necessary for effusions or cardiac tamponade.
Pericardial effusion/ Cardiac tamponade/Hemopericardium
Fluid accumulation in the pericardium
Rapid increase in intrapericardial pressure, resulting in compression of the heart, and thereby a restriction of cardiac
inflow (filling), is called Cardiac Tamponade
Etiology:
Idiopathic
Infectious
 Viral Hemopericardium
 Tuberculosis Blood in the pericardium
 Pyogenic Bacterial Chest Injury
Injury Coagulopathy
 Organ: AKI/CKD
 Chest trauma
Immune:
 Collagen-vascular diseases
 Post CABG
 Postmyocardial infarction
Malignant effusion
Symptoms:
Asymptomatic (Small effusion)
Symptomatic: The intrapericardial pressure determines to what extent
Breathlessness cardiac inflow is decreased; intrapericardial pressure
Chest pain & discomfort depends not only on the amount of fluid that
Collapse accumulates, but also on the rate with which this
Dizziness accumulation proceeds, and the available distensibility
Signs: of the pericardium.
1. Hemodynamic instability: Tachycardia, hypotension Chronic effusions may therefore lead to small increase
2. Jugular pressure: distension in intrapericardial pressures even in the presence of
3. Pulsus paradoxus may be present. large fluid accumulations, and rapid but small
4. Auscultation: accumulations may directly lead to severe cardiac
 may reveal pericardial friction rub tamponade.
 Heart sounds may be faint/muffled
Investigations:
1. Echocardiography shows pericardial effusion
2. Anaylsis of pericardial fluid: Cytological/ Microbiological/ Biochemical tests
3. Other relevant tests to assess the underlying disease
Treatment:
1. Pericardiocentesis: therapeutic fluid aspiration/ drain
 Asymptomatic Small to medium effusion: Not required
 Tamponade/ moderate to severe effusion: Urgent Pericardiocentesis
2. Hemeopericardium: Blood transfusion
3. Treat the underlying cause
Hypertension
Hypertension in adults age 18 years and older is defined as systolic blood pressure (SBP) of 140 mm Hg or greater
and/or diastolic blood pressure (DBP) of 90 mm Hg or greater
Types:
Primary Secondary:
Essential Hypertension Aortic disease:

 Coarctation of aorta
 Aortoarteritis
Bad sleep: Obstructive sleep apnoea
Chronic Renal diseases:
 Renal artery stenosis
 Renoparenchymal disease( CKD due to any causes)
 Polycystic Kidney disease
 Glomerulonephrtits
Drugs: OCP/Steroid/Cyclosporine/NSAIDs
Endocrinopathy
 Pituitary: Acromegaly
 Adrenal
 Cushing
 Conn syndrome (primary Hyperaldosteronism)
 Pheochromocytoma
 Thyroid: Hypo/ Hyperthyroid
Parathyroid: Hyperparathyroid
Assessment of Hypertensive Patient:
Aims:
1. To look for Hypertensive manifestations
2. To look for any complication: these may be present on first presentation or may develop later
3. To look for any other Atherosclerotic(Vasculopathic) Risk factors
5. To look for any secondary causes of Htn
1. Hypertensive symptoms:
 h/o headache  h/o Palpitation
 h/o Visual disturbances  h/o Irritability
 h/o Neck painPolydipsia
2. Symptoms suggesting development and severity of complications: evidence of Target Organ damage (TOD)
1. Cerebrovascular disease: h/o TIA/CVA
2. Coronary artery disease: h/o Angina/ MI
3. Peripheral vascular disease
 h/o Claudication
4. Nephropathy (Kidney disease):
 h/o swelling: Any Facial puffiness/Any Pedal edema
 h/o decreased urine output
 h/o breathlessness
5. Retinopathy:
 h/o retinopathy
 Any visual disturbance
4. Risk factors for atherosclerosis:
 Activity status: exercise lack  Cigeratte smoking
 BMI: obesity  Dyslipidemia
 Eating pattern
 Current treatment & BP status: medications, compliance
6. Evaluation for possible causes of secondary Hypertension: particularly in Young hypertensive.
Examination: Important findings with their clinical relevance:

 Arterial pulse: poor peripheral pulses: Peripheral vascular disease
 BMI high: atherosclerotic risk factor
 BP: status of BP control
 BP: Lying and standing: Postural drop: Antihypertencive drug side effects
 Cardiac: Gallop/Basal crackles: heart failure
 CNS: focal neurodeficit: CVA/TIA
 Edema: CKD/CCF
 Eye: Fundoscopy: To look for retinopathy: ophthalmoscopic evaluation by ophthalmologist
 Signs of secondary hypertension
1. Radio-femoral delay: Coarctation of Aorta
2. Renal artery Bruit: Renal Artery stenosis
3. Plaplable Kidneys: Polycystic kidney disease
4. Signs of Cushing syndrome
Investigations:
To look for complications: Exact nature and frequency of these tests depend on presence/absence of complications,
1. CBC: Hb, TC,DC, ESR: Hb: Low: may be due to CKD
2. Serum Urea creatinine: raised: CKD
3. Urine analysis: To assess Albuminuria
 Urine dipstick analysis: Proteinuria
 Urinary Microalbumin- Creatinine ratio( MACR): To assess Albuminuria
4. ECG
5. Echocardiography
6.USG Kidneys: with Renal artery Doppler: To assess Kidney size and Renal artery stenosis
To look for atherosclerotic risk factors:
1. Glycemic profile: FBS/PPBS/HbA1c
2. Lipid profile
Treatment:
Treatment of Htn
BP control Treatment of complications Treatment of atherosclerotic risk factors (if present)

depends on complication(s) Activity status: exercise lack
Lifestyle Pharmacotherapy BP: Hypertension
modification Antihypertensives BMI: obesity 1. Lifestyle modifin
1. Diet Oral Cigeratte smoking 2. Drugs
2. Exercise Injectibles (in case of an emergency) Dyslipidemia
BP control
Diet: Avoid added salt and presalted foods: Pickles/ salted nuts
Drugs Antihypertensive Drugs:≥ 1 of the following drugs depending on the clinical condition/ type of heart failure
Choice of drug (s) depend on following factors:
● Age ● Contraindication
● BP status ● Duration of Htn
● Comorbidities: Often the most important factor behind the selection of the class of antihypertensive
● Complications: present or absent ● Education status
Different classes of antihypertensive drugs:
4. Alpha Blockers: Prazocin/ Terazocin
5. β-blocker: Metoprolol/ Carvedilol (α+β1 blocker)/Bisoprolol
a. They should be started cautiously at a low dose and then uptitrated gradually.
6. Calcium channel blocker (CCB): Dihydropyridine: Cilnidipine/ Amlodipine/ Nifedipine
7. Centrally acting: Clonidine/ Alpha Methyldopa
8. Diuretics: Furosemide/Torsemide/ Bumetanide.
9. Dilator: Vasodilators:
 Venodilator: Reduces preload: Oral Nitroglycerine/ GTN
 Arteriolar dilator: Reduces afterload: Hydralazine.
10. Direct Renin Inhibitor: Aliskiren (ALMOST obsolete!!)
Hypertensive Urgency/ Hypertensive Emergency/ Hypertensive Crisis/ Malignant hypertension/ Accelerated HTn
(“Overall” more or less same, minor difference between them, so “overall” Ans. remains the same)
Hypertensive Emergency/ Malignant hypertension/Accelerated hypertension
Severe hypertension (often SBP >220 mm Hg and/or DBP >120 mm Hg) with ACUTE impairment of an organ system/
rapidly developing target organ damage typically CNS and/or cardiovascular and/or renal, requiring substantial
reduction of blood pressure within one hour to avoid the risk of serious morbidity and death.
Blood pressure is often severely raised, but is always a poor correlation between pressure and endorgan damage.
While hypertensive urgency is severe hypertension (often SBP >220 mm Hg and/or DBP >120 mm Hg) but lack of end
organ damage.
Hypertensive emergencies are associated with the following:
• Neurological deficits primarily presenting as TIA, hypertensive encephalopathy, intracranial hemorrhage and stroke
• Cardiovascular complications such as pulmonary edema, acute myocardial infarction, dissecting aortic aneurysm
• Eclampsia
• Renal complications as hematuria and progressive renal dysfunction
• Optic disk edema
In these conditions, the blood pressure (BP) should be lowered aggressively over minutes to hours.
Hypertensive crisis is defined as having a SBP >220 mm Hg and/or DBP >120 mm Hg with optic disk edema OR
progressive target organ complication OR severe perioperative hypertension.
Pathophysiology: 3 major organ systems affected by high BP are the central nervous system, cardiovascular system,
and renal system.
CNS: elevated BP overwhelms the normal cerebral autoregulation.
CVS: increased cardiac workload leads to cardiac failure; this is accompanied by pulmonary edema, myocardial
ischemia, or myocardial infarction.
Renal: renal system is impaired when high BP leads to arteriosclerosis, fibrinoid necrosis, and an overall impairment of
renal protective autoregulation mechanisms.
Treatment: Drugs who can lower BP rapidly and effectively: so most of these are IV agents, some are oral rapid
acting
Ideally the drug of choice varies according to the specific situation associated with severe hypertension however often
“resource” issue takes precedence over “medical” issue. Overall following are rapidly effective drugs:
Parenteral agents: Oral agents:
ACEi: Enalaprilat Captopril (Sublingual)
Alpha+ beta blocker: Labetalol Nifedipine (“pierce” the cap and squeeze the gel sublingually)
Beta blocker: Esmolol
CCB: Nicardipine/Clevidipine (‘Real world’ tips: Often you would not get hold of any 1 of these
Dilators: Nitroprusside/Hydralazine/Nitroglycerine in ward/Medicine shop, so IMPROVISE: give rapid acting oral
Dopa agonist: Fenoldopam Nitrate: “Sorbitrate” sublingually!!)
Secondary Hypertension: approach
 How will you approach a suspected case of secondary Hypertension

 A young (<30 yrs.) patient has been diagnosed with Hypertension
 Pediatric age group patient has been diagnosed with Hypertension
Causes:
Aortic disease:
 Coarctation of aorta
 Aortoarteritis
Bad sleep: Obstructive sleep apnoea (OSA)……………..NOT A CAUSE for PAEDIATRIC AGE GROUP!!
Chronic Renal diseases:
 Renal artery stenosis
 Renoparenchymal disease( CKD due to any causes)
 Polycystic Kidney disease
 Glomerulonephritis
Drugs: OCP/Steroid/Cyclosporine/NSAIDs
Endocrinopathy
 Pituitary: Acromegaly
 Adrenal
 Cushing
 Conn syndrome (primary Hyperaldosteronism)
 Pheochromocytoma
 Thyroid: Hypo/ Hyperthyroid
 Parathyroid: Hyperparathyroid
History: Important clue it gives

Flushing: Pheochromocytoma Hematuria: Glomerulonephritis
Headache: Acromegaly Daytime sleepiness: OSA
h/o Labile(= fluctuating) BP: Pheochromocytoma Snoring: OSA
Palpitations: Pheochromocytoma/Thyrotoxicosis Cold/heat intolerance: Thyroid
Syncope: Tachyarrhythmia: Pheochromocytoma/Thyrotoxicosis Constipation/diarrheaa: Thyroid
Sweating: Pheochromocytoma/Thyrotoxicosis Weight gain: Cushing/Hypothyroid
Weight loss: Thyrotoxicosis Tremor: Thyrotoxicosis
Irregular/heavy or absent menstrual cycle: Endocrinopathies
Drug: Regular use of Steroids/ Sympathomimetic/Estrogen/NSAIDs
Signs: Important clue it gives

Acromegalic appearance: Acromegaly R-E delay or poor femoral pulses: Coarctation
Buffalo hump: Cushing Goitre: Thyroid disease
Central obesity: Cushing Thyroid eye signs: Thyrotoxicosis
Moon facies: Cushing Palpable kidney(s): Polycystic kideny
Striae: Cushing Renal artery bruit: Renal artery stenosis
Fine tremor: Thyrotoxicosis
Bradycardia/tachycardia: Thyroid disorder/Pheochromocytoma
Irregular pulse: AF- Thyrotoxicosis/Pheochromocytoma
Arm to leg systolic blood pressure difference > 20 mm Hg: Coarctation
Investigations: Following are the tests and diagnosis they help to arrive at-
Urine Routine: RBC cast- Glomerulonephritis
USG KUB: Polycystic kidney/Renal artery stenosis  Thyroid function test: thyroid diseases
Renal Biopsy: Pattern of Glomerulonephritis  Dexamethasone suppression test: Cushing
Echocardiography: Coarctation  IGF1 level: Acromegaly
Endocrinopathy related investigations:  GH estimation following Oral Glucose load: Acromegaly
 Urinary metanephrine level: Pheochromocytoma
Valvular & Congenital Heart diseases: overview
Valvular defect Congenital Heart disease
Incomplete opening: Stenosis Congenital Valvular defect Nonvalvular defect

Incomplete closure: Incomptenece/Regurgitaton Septal Defects
PDA
Coarctation of aorta
Stenosis/ Regurgitaton may occur in Congenital Heart disease may be
Single valve Multiple valves 1.Valvular ONLY 2.Non valvular only 3.Combination of both
1 type of defect
Or both defects (Mixed valvular heart disease)
Any valve= Front or back door with respect to a CHAMBER
 Stenosis: FRONT door of a chamber is NARROW = fixed outflow obstruction with respect to that chamber
 Incompetence: BACK door of a chamber is LEAKY, so blood will backflow from that chamber to another
chamber for which that valve is actually the FRONT door
 Septal defect: Shunting of blood through the defect, so the chamber receiving that shunted blood has to deal
with Extra amount of blood
So in stenosis So in Incompetence & Septal defect:

A particular chamber
Chamber is having fixed outflow obstruction Chamber has to deal with Extra amount of blood
Pressure overload Volume overload
Dilatation/Hypertrophy
Dysfunction Arrhythmogenicity
Cardiac failure Tachyarrhythmias
Left heart Right heart Atrial origin Ventricular origin

MV disease: Left Atrial dysfunction TV disease Right Atrial dysfunction
AVdisease Left Ventricular dysfunction PV disease Right Ventricular dysfunction
Clinical manifestation
ANY Valvular/Congenital HD
Septal Endocardium
Breathlessness+/- Orthopnoea+/- PND Edema Blackout (syncope)
Murmurs…see general discussion on Cardiac signs
Investigation of VHD/CHD (details in general discussion on Cardiac investigations…a quick recap!!)
ECG/24 hours Holter Blood C/S
Echocardiography Procalcitonin
Blood Pro BNP/NT-Pro BNP/BNP level
CBC/CRP
Treatment of VHD/CHD
Rx of Heart failure Rx of Arrhythmia Rx of Endocarditis Cardiac surgery
Valvular Heart disease Congenital HD
Valve replacement Correction of the defect
Prosthetic (artificial) valve technique

Made of
Bio(Tissue)Prosthesis Metallic prosthesis Interventional Cardiological Surgical
AORTIC REGURGITATION (AR)

Incomplete closure of aortic valve
Etiology:
Primary/Organic: AR due to valvular defect
• Chronic Rheumatic valvular Heart Disease
• Infective Endocarditis
Secondary/Functional: Due to aortic root dilation: Root dilatation Aortic ring dilatation Separation of valve
cusps Incomplete closure
• Aortitis (Syphilitic) Ankylosing spondylitis
• BP: Long standing Hypertension
• Bone: Osteogenesis imperfecta
• Connective tissue: Marfan's syndrome
Hemodynamics:
Cardiac effects:
AR Incomplete closure of AV Gap remaining from the very beginning of Diastole Diastolic “back flow” from
Aorta to LV( early diastolic murmur) LV end diastolic volume increases as it receives blood from “dual” source:
from LA and additional amount from regurgitating from Aotra LV volume overload…..LV dysfunction
“Backward effect” Pulmonary Congestion Pulmonary edema long standing cases PAH RV work load
increase RV enlargement and dysfunction
Hemodynamics of aorta and other arteries:

1. Abrupt systolic distension due to increased stroke volume as LV end diastolic volume increases
2. Rapid diastolic collapse due to diastolic backflow of blood from Aorta (& therefore entire arterial tree) towards LV
These 2 hemodynamic effects are responsible the peripheral signs of AR
Symptoms: appear when significant Cardiac Dysfunction sets in
AR
Septal Endocardium
Dizziness
Galloping of heart (Palpitation)
Signs: ≥ 1 of the followings depending on patient’s Cardiac status
1. Hypoxic/ Tachypnoeic: due to Pulmonary edema (LVF)
2. JVP↑ (due to RVF: occurs in late stage due to long standing LHF)
3. Oedema (due to RVF: occurs in late stage due to long standing LHF))
4. Cardiac examination:
Signs depend on presence/absence of Heart failure!!
S1: Normal
S2: soft/inaudible A2 (incomplete closure of AV)
S3: once significant LV dysfunction occurs
5. Murmur:
“Primary” (organic) murmur:
Neoaortic/ Aortic area: Murmur of AR: early-diastolic murmur, soft blowing in quality; the sound may be accentuated
by asking the patient to sit in a leaning forward position & holding the breath after deep expiration. It propagates along the
left sternal border towards mitral area.
Functional/Innocent/flow murmur:
1. A mid-systolic murmur may be heard due to functional AS (during ventricular systole abnormal amount of blood
flows from LV through Normal Aortic opening)
2. Pansystolic murmur over Mitral area due to functional MR secondary to LV dilatation which dilates and separates
the ring and cusp of the mitral valve
3. Mid diastolic murmur over Mitral area due to functional MS: regurgitant jet from Aorta to LV may hit one of the
cusps of MV in a such a way that it prevents the cusp from opening ( Austin flint murmur)
6. Peripheral signs (signs present over peripheral arteries)

1. Episodic head nodding with each systole (De Musset sign) All time favourite of some “….”!!
&
2. Prominent carotid pulsation (Dancing carotid/ Corrigan’s sign)
of some “baby Final MBs”!!
3. High volume collapsing pulse (Water hammer/Corrigan’s pulse)
4. BP: wide pulse pressure PS: atleast 10 more peripheral signs are there!
 SBP ↑/Normal
 DBP ↓.(due to diastolic run off)
As the severity & duration of AR progresses, LV function strats to get compromised so SBP may be normal/ low
normal and DBP doesn’t fall to the extent it was falling during early stage.
5. Hill’s sign: Normally femoral arterial SBP is higher than brachial arterial SBP. The difference is usually <20 mm Hg.
But in AR, this difference becomes >20 mm Hg.
6. Auscultation of femoral artery:
a. Pistol shot sound: A booming sound with each systole with abrupt systolic distension of femoral artery.
b. Duroziez murmur: On distal compression of femoral artery with diaphragm of the stethoscope, a diastolic
murmur can be heard
Investigation
1. CBC. Alternative format
2. Urea-creatinine Na+ K+ Definitive Investigation: Echo
3. ABG (if hypoxic) Supportive investigations: To look for complications
4. Blood C/S: if endocarditis is suspected 1. CBC
5. NT Pro BNP/Pro BNP: if heart failure is suspected 2. Urea-creatinine Na+ K+
6. CXR: May show cardiomegaly 3. ABG (if hypoxic)
7. ECG +/- 24 hours Holter: to look for arrhythmia 4. Blood C/S:
8. Echocardiogram: 5. NT Pro BNP/Pro BNP
a. Confirms the diagnosis & severity 6. CXR
b. Assesses cardiac chamber size &cardiac function 7. ECG +/- 24 hours Holter
Treatment
a. Medical management: Treatment of complications: 1. Heart failure 2. Arrhythmia 3. Endocarditis
b. Interventional treatment
Medical management:
1. Treatment of LHF: depending on the severity of heart failure ≥ 1 of the followings
A: Airway: Intubation as some patients need Ventilatory support for severe hypoxia
B:
 Bed rest
 Breathing support: O2/ Ventilatory support: Non invasive or Invasive
C:
 Circulation: Inotopic support for Hemodynamic instability due to severe LV dysfunction
 Catheter to monitor urine output
D:
Diet: Fluid and salt restriction
Drugs: “Anti failure drugs”: ≥ 1 in varying combination
 A: ACE inhibitors/ ARB
 B: Beta blocker
 C: CCB
 D: Diuretic
Dilators
Venodilators: Nitrate/Nitroglycerine: reduces preload
Arterial dilator: Hydralazine: reduces after load
2. Treatment of Arrhythmia: Ventricular tachyarrhythmias:
A: Amiodarone
B: Betablocker
C: Cardioversion (Electrical)
3. Treatment of Endocarditis: Antibiotic
Interventional treatment: Aortic valve replacement
Causes of Early diastolic murmur over Neoaortic/aortic area (EDM)
Murmur produced across AV and heard over Aortic area
a. Valvular AR of ANY etiology: Valvular defect/ Functional AR
Diastolic murmur produced across another valve but heard over neoaortic/aortic area
1. Murmur of PR 2.Murmur of MS 3.Murmur of PDA
Complications of AR
 LVF: May be chronic/ acute on chronic
 RVF: secondary to long sanding LVF
 Ventricular arrhythmia: Syncope
AORTIC STENOSIS (AS)
Incomplete opening of aortic valve
Etiology:
A. Age related degeneration of the valve
B. Bicuspid aortic valve (congenital defect: so commonly seen in young patients
C. Calcific degeneration of aortic valve (also called aortic sclerosis)
D. Deformity: chronic rheumatic valvular heart disease).
Hemodynamics: Cardiac effects:
1. Backward effects: AS Incomplete opening of AV LV pressure overload due to narrow opening LV
dysfunction LV end systolic volume increases “Backward effect” LA congestion Pulmonary Congestion
Pulmonary edema long standing cases PAH RV work load increase RV enlargement and dysfunction
2. Forward effect of AS: Initially cardiac output (CO) is maintained but eventually it falls, resulting in low volume
pulse and low BP.
Symptoms: Symptoms: appear when significant Cardiac Dysfunction sets in

AS
Septal Endocardium
Dizziness
Galloping of heart (Palpitation)
Blackout in AS:
 Due to Arrhythmia: LV Enlarged, so fibres get stretched/ scarred and may become electrically hyperexcitable
 Due to a sudden fall of CO below a critical level due to sudden “locking” of a tight aortic valve
Signs: ≥ 1 of the followings depending on Cardiac status

1. Hypoxic/ Tachypnoeic: due to Pulmonary edema (LVF)
Apical impulse:
 Normal or Forceful and well sustained (heaving)
Mechanism: Forceful due to increased LV force of contraction and well sustained because of prolonged LV systolic
ejection time: BOTH due to fixed LV outflow obstruction
 May be shifted down and out (due to LV hypertrophy)
S1: Normal
S2: Normal
S4: may be present (once significant LV dysfunction occurs)
Ejection click (“Opening snap” of AS): The ejection click usually precedes the mid-systolic murmur and occurs
due to sudden vibration produced during opening of thickened aortic valve.
Murmur of AS:
 A mid-systolic murmur( No blood flow through AV during early systole) Loud in intensity (harsh blowing
murmur). It usually propagates towards carotid as the direction of turbulence is from LV to Aorta
Investigation
2. Urea-creatinine Na+ K+
3. ABG (if hypoxic)
Refer to AR!!!
4. Blood C/S: if endocarditis is suspected
5. NT Pro BNP/Pro BNP: if heart failure is suspected
6. CXR: May show cardiomegaly
7. ECG +/- 24 hours Holter: to look for arrhythmia
8. Echocardiogram:
 Confirms the diagnosis & severity
 Assesses cardiac chamber size &cardiac function
Treatment
Medical management: Treatment of complications: 1. Heart failure 2. Arrhythmia 3. Endocarditis
Interventional treatment
Medical management:
1. Treatment of LHF: depending on the severity of heart failure ≥ 1 of the followings
A: Airway: Intubation as some patients need Ventilatory support for severe hypoxia
B:
 Bed rest
 Breathing support: OM: Morphine
C:
 Circulation: Inotopic support for Hemodynamic instability due to severe LV dysfunction
 Catheter to monitor urine output
Drugs: “Anti failure drugs”: ≥ 1 in varying combination
 A: ACE inhibitors/ ARB
 B: Beta blocker
 C: CCB
 D: Diuretic
Dilators:
Venodilators: Nitrate/Nitroglycerine: reduces preload
Arterial dilator: Hydralazine: reduces after load
2.Treatment of Arrhythmia: Ventricular tachyarrhytmias:
A: Amiodarone
B: Betablocker
C: Cardioversion (Electrical)
Interventional treatment: Aortic valve replacement.
Complications of AS
 LVF: May be chronic/ acute on chronic
 RVF: secondary to long sanding LVF
 Ventricular arrhythmia: Syncope
 Sudden death:
a. Stenosed aortic valve refuses to open at all, leading to sudden irreversible fall of CO.
b. Sudden fatal Ventricular arrhythmia arising from stretched ventricular myocardium.
Causes/DD of Systolic murmur over aortic area
1. Systolic murmur produced across AV and heard over aortic area
1. Valvular AS MSM of valvular AS MSM of functional AS
2. Functional AS: As in Ejection click usually present Ejection click absent
Any hyperkinetic circulatory state: carotid propagation usually present dose not propagate to Carotid
 AR
 Anemia Functional AS: an All time favourite of some “….”!!
&
 Beri beri
of some “baby Final MBs”!!
 “Conceive”: Pregnancy
 D: Ductus Arteriosus Patent (PDA)
 Endocrinopathy: Thyrotoxicosis
 Fever
2. Systolic murmur produced across another valve but heard over Aortic area: Murmur of MR/ VSD/PS
MITRAL STENOSIS (MS)

Incomplete opening of mitral valve.
Causes of mitral stenosis:
1. Chronic Rheumatic heart disease
2. Rare causes include: ● Congenital MS ● Hurler’s syndrome
Hemodynamic effects of MS:

Incomplete opening of MV LA outflow tract obstruction Chronically increased LA pressure eventually
LA dilation and hypertrophy
LA dilates, the fibres of LA are stretched & scarred Eventually LA failure results
these areas become electrically hyper-excitable & backward effect of LA failure
may start to “bombard” Fast & erratic Electrical impulses Pulmonary Congestion
Arrhythmia: Atrial fibrillation (AF) Pulmonary edema(LHF)
AF No organized Atrial Systole long standing Pulmonary Congestion
Stagnation of blood in LA PAH
formation of LA clot RV work load increase
Embolism (stroke) RV enlargement and dysfunction (RHF)

MS
Septal Endocardium
Rare symptoms of MS (“Final MB type!!) Embolism: Stoke
 Hemoptysis: As PAH increase collaterals are formed between branches of pulmonary artery and bronchial artery.
These collaterals (RARELY!!) rupture; giving rise to hemoptysis
 Hoarseness (due to recurrent laryngeal nerve compression/ palsy by a dilated LA)
 Dysphagia (due to compression of oesophagus by a dilated LA).
1. Hypoxic/ Tachypnoeic: due to Pulmonary edema (LAF)
4. Pulse:
 Completely irregular pulse (if AF)
AF is VERY COMMON in Mitral Valve disease
 Heart rate: Tachycardia
Apical impulse:
 Site: Normal or shifted to outwards in late MS (due to RVH)
 Character: Normal or tappine.
Thrill: if present diastolic thrill Loud S1: As diastole progresses MV cusps passively start to come close to each
Heart sound: other. In MS, the LA pressure is raised; so the pressure gradient between LA and LV
 S1: loud is higher than a normal heart; so passive movement of cusps during diastole cannot
 S2 is usually normal occur so the final closure takes place from a greater distance in comparison to the
 Opening snap (OS): present “final closure” distance of a normal MV
S1 may be soft; when the valves are damaged severely and the cusps become
immobile
 Murmur: Murmur of MS
Mid-diastolic with pre-systolic (Late diastolic) accentuation Rumbling (“quality” of sound) better heard over mitral
area in left lateral position at the end of expiration Mid-diastolic: No blood flow through MV in Early diastole
6. Signs of PAH Pre-systolic (Late diastolic) accentuation: LA contraction
(for “Final MB!!) during last rapid filling phase of ventricular diastole (which is
Pulmonary area: if MS is associated with PAH actually just before the next ventricular systole hence the name
1. Accentuated P2 + palpable P2 may also be present. pre-systolic). May be absent in AF
2. Flow murmurs:
Mid-systolic murmur (abnormal “pattern” of blood flow through the normal pulmonary valve during systole
Graham steel murmur: Early diastolic murmur due to functional PR secondary to pulmonary ring dilation caused by
long standing PAH may be present
Tricuspid area: Pansystolic murmur may be present. (due to functional TR secondary to tricuspid ring dilation caused
by right ventricular dilation)
Opening snap (OS): {for “Final MB”!!!}
An abnormal EARLY DIASTOLIC sound produced due to sudden halting of the diastolic descent of rigid (stenosed)
MV cusps.
Significance of opening snap: More is the severity of MS, higher is the LA pressure & earlier will be the diastolic
descent so, earlier will be it’s halting & earlier will be the OS
The gap between S2 and OS varies according to the severity of MS: NARROWER the gap MORE is the severity of MS.
So, S2-OS gap is a marker of severity of MS
Investigation
2. Urea-creatinine Na+ K+
3. ABG (if hypoxic)
Refer to AR!!!
4. Blood C/S: if endocarditis is suspected
5. NT Pro BNP/Pro BNP: if heart failure is suspected
6. CXR: May show cardiomegaly
7. ECG +/- 24 hours Holter: to look for arrhythmia
8. Echocardiogram:
 Confirms the diagnosis & severity
 Assesses cardiac chamber size & cardiac function
 Will show LA clot, if present
Treatment
Medical management: Treatment of complications: 1. Heart failure 2. Arrhythmia 3. Endocarditis
Interventional treatment
Medical management:
1. Treatment of LHF: Refer to previous sections!!
2. Atrial fibrillation: 2 important strategy
Antiarrhythmic Rx Anticoagulation
Not all need treatment, if treatment indicated 1 DECIDING factor is Depending on CHADSVAsc score
some will be eligible
Hemodynamically unstable Hemodynamically stable for anticoagultion
Electrical cardioversion Rhythm conversion 1.Warfarin
Pharmacological cardioversion Pharmacological 2.Non VKA
Amiodarone Amiodarone Dabigatran
Flecainide Rivaroxaban
Rate control: Atrial activity remains
CHAOTIC (AF continues) but
Elective electrical cardioversion Rhythm conversion/Cardioversion:
VENTRICULAR rate is slowed down Rate control Convert the rhythm into sinus rhythm
Beta blocker (atrial & ventricular activity goes back
under SA node)
CCB
Digoxin
Interventional treatment: Mitral valve replacement

Complications
1. Atrial fibrillation +/ emboli formation 4. Right heart failure (RHF)
2. Left Heart failure: Acute pulmonary edema 5. Infective endocarditis (IE)
3. Pulmonary arterial hypertension (PAH)
Causes of / DD of Diastolic murmur over mitral area

1. Diastolic murmur produced across MV and heard over Mitral area
1. Valvular MS
2. Functional MS: In / AR/ VSD (abnormal amount of blood flowing through a normal MV during diastole)
3. Temporary valvulitis of MV during an episode of acute rheumatic fever (causing transient MS)
2. Diastolic murmur produced across another Valve but heard over Mitral area
1. Murmur of TS
2. Murmur of AR
MITRAL REGURGITATION (MR)
Incomplete closure of the mitral valve
Causes:
1. Organic/ Valve defect: 2. Functional MR: Mitral valve ring/ annulus defect:
a. Rheumatic Valvular heart disease any condition causing LV dilation, may cause stretching
b. Infective endocarditis of mitral valve ring leading to separation of cusps and
c. Calcific degeneration of mitral valve incomplete closure
d. Chordi tendon rupture: AMI
e. Papillary muscle rupture: AMI
Hemodynamic effects of MR:

On LA
Incomplete closure of MV Back flow of blood from LV to LA from the beginning of Systole and continues
throughout the systole LA volume overload as it receives blood from “dual sources”: Normal quota from Lungs
and additional amount from LV Chronically increased LA pressure eventually
LA dilation and hypertrophy
LA dilates, the fibres of LA are stretched & scarred Eventually LA failure results
these areas become electrically hyper-excitable & backward effect of LA failure
may start to “bombard” Fast & erratic Electrical impulses Pulmonary Congestion
Arrhythmia: Atrial fibrillation (AF) Pulmonary edema(LHF)
AF No organized Atrial Systole long standing Pulmonary Congestion
Stagnation of blood in LA PAH
formation of LA clot RV work load increase
Embolism (stroke) RV enlargement and dysfunction (RHF)
On LV
LV undergoes a volume overload as well, as during next diastole this additional amount of blood will flow from LA to
LV so LV undergo dilation/ hypertrophy and eventually becomes dysfunctional backward effect of LV failure
LV congestion Pulmonary Congestion(Pulmonary edema) long standing cases PAH RV work load
increase RV enlargement and dysfunction
MR
Septal Endocardium
Rare symptoms of MR (“Final MB type!!) Embolism: Stoke
 Hemoptysis: As PAH increase collaterals are formed between branches of pulmonary artery and bronchial artery.
These collaterals (RARELY!!) rupture; giving rise to hemoptysis
 Hoarseness (due to recurrent laryngeal nerve compression/ palsy by a dilated LA)
 Dysphagia (due to compression of oesophagus by a dilated LA).
1. Hypoxic/ Tachypnoeic: due to Pulmonary edema (LAF)
4. Pulse:
 Completely irregular pulse (if AF)
AF is VERY COMMON in Mitral Valve disease
 Heart rate: Tachycardia
5. Cardiac examination
Mitral area
Apex:
Site: Normal or Downwards and outwards shifting of apical impulse due to LV dilation:
Character: Normal or Forceful ill sustained apical impulse.
Mechanism: Forceful to counteract the volume overload and ill sustained due to shortening of LV systolic ejection
time (as there are 2 outlets of blood during systole of LV).
Thrill over mitral area may be present, systolic in timing.
Heart sounds:
S1 is muffled and soft Because the valve closure in mitral regurgitation is incomplete
S2: Normal
S3: may be present
Murmurs:
Primary/ Organic murmur: Murmur due to MR:
Pan-systolic soft blowing murmur over mitral area, best heard when patient is on left-lateral position. The murmur
usually propagates towards the axilla (due to the posteriorly faced right atrium).
Associated murmur (Flow/Functional/Innocent murmur):
Mid-diastolic murmur due to a functional MS may be found (Incresed amount of blood flow through Mitral valve
during diastole)
Investigation
Treatment
Refer to AR/AS/MS!!!
1. Medical management: Treatment of complications: 1. Heart failure 2. Arrhythmia 3. Endocarditis
2. Interventional treatment
Causes/DD of Systolic murmur over mitral area
Produced across Mitral valve Produced ELSEWHERE but transmitted to Mitral area
1. Valvular MR. 1.TR
2. Functional MR 2.VSD
Propagation of pan-systolic murmur in MR

1. Axilla: As the direction of turbulent blood flow is from LV to LA and the LA is usually located posteriorly in the
body, therefore the sound propagates from mitral area towards the axilla near which LA is situated.
2. Aortic area: It occurs when the regurgitant stream hits that point of LA wall that is adjacent to the aorta. It is seen
when predominantly the posterior cusp of mitral valve is affected.
Complications
1. Atrial fibrillation +/ emboli formation 4. Right heart failure (RHF)
2. Left Heart failure: Acute pulmonary edema 5. Infective endocarditis (IE)
3. Pulmonary arterial hypertension (PAH)
CONGENITAL HEART DISEASES
Tetralogy of Fallot
4 components of the “tetralogy”:
1. Pulmonary stenosis (PS).
2. Right ventricular hypertrophy (RVH).
3. VSD.
4. Septal overriding of aorta (in some patients, there may be right ventricular origin of aorta).
Hemodynamics:
Level Hemodynamics
Pulmonary valve Turbulent blood flow.
Right ventricle 1. RVH (secondary to PS)
2. Due to PS, RV pressure remains significantly high since the time of birth and it
becomes > LV pressure soon after birth/ during early stages of life; which is
responsible for right to left shunt through the ventricular septal defect.
3. During systole, RV gets decompressed faster as there are 2 outlets through which
blood can flow out of RV (pulmonary valve and LV). So, RV dysfunction/ failure is
relatively uncommon in TOF.
4. The severity of PS is the indicator of the severity of the disease.
Pulmonary valve Turbulent blood flow during systole
Left heart It is largely unaffected as there is neither volume nor pressure overload.
Symptoms:
1. Anoxic spells:
 Duration, frequency and severity of anoxic spells depend on the amount of right to left shunt.
 The child is usually restless, irritable, drowsy and cyanotic.
 Exercise often precipitate severe anoxic spells (as venous return is increased in exercise and that results in
increased right to left shunt).
 Squatting may temporarily relief the baby by the following mechanism:
Squatting leads to
 Increased total peripheral resistance Increased LV pressure Reduced Right to Left shunt flow
 Increased Peripheral (venous) pooling of blood Reduced Venous return So Hypoxia temporarily corrected
Signs:
1. Hypoxic: Tachypnoeic/ Loe O2 saturation/Cyanosis
2. Mid-systolic murmur over pulmonary area due to PS
Investigation: Echocardiogram: Confirms the diagnosis.
Treatment
1. Symptomatic relief during anoxic spells:
a. Put the baby on a squatting posture
b. high flow oxygen.
2. Surgical correction of the underlying defect.
3. Palliative surgery: Anastomosis is created between a systemic artery and one of the branches of pulmonary artery
so that deoxygenated blood can be redirected to lungs for oxygenation.
Various palliative shunts applied in TOF: Potts shunt/ Blallock- Taussig shunt
Name of the shunt Applied in between

Potts shunt Descending aorta connected to left pulmonary artery
BT shunt A tube graft placed between subclavian artery and one of the pulmonary arteries
Complications
1. Severe anoxic spells
2. Infective endocarditis
3. Recurrent broncho-pulmonary infection
VSD (Ventricular septal defect)
Gap in the Interatrialventricular septum
1. Congenital: Development defect of septum
2. Acquired: Post MI rupture of septal wall
Hemodynamic abnormality:
At the level of VSD: Left to right shunt along the pressure gradient (LV to RV) continues throughout the Cardiac cycle
however turbulence is significant throughout the systole only as Diastolic pressure gradient is not significant
enough to produce a murmur.
Hemodynamics at different levels:

Level Hemodynamics
RV Volume overload--- RV dysfunction/ failure.
Eventually a time might come when RV pressure will be greater than LV pressure; causing
reversal of shunt
Pulmonary valve Functional PS (abnormal blood flow through a normal valve)
Pulmonary artery PAH
LA Volume overload--- LA failure.
MV Functional MS (abnormal blood flow through a normal valve).
LV Volume overload---LV failure
1. Asymptomatic
2. Breathlessness=/- Orthopnoea=/- PND due to LHF
3. Edema: due to RHF (at very late stage
Signs:
1. Sign of RHF: JVP↑/Edema)
2. Hypoxia + Basal crepts: signs of pulmonary congestion)
3. S1 & S2: gets obscured by the murmur
4. Murmur:
a. Due to VSD: A loud pan-systolic murmur best heard over left 4th intercostal space. It’s so loud that it is often audible
at all other cardiac areas
b. Associated murmurs:
 MSM at pulmonary area (due to functional PS)
 MDM at mitral area (due to functional MS)
Investigation: Echocardiogram: Confirms the diagnosis.
Treatment
1. Medical management of underlying heart failure
2. Surgical correction of VSD
ASD (Atrial septal defect)
Development defect of Interatrial atrial septum
Types of ASD:
1. Ostium secondum type: Common variety; defect lies at the level of fossa ovalis.
2. Ostium primum type: Defect lies inferior to fossa ovalis.
Hemodynamics:
At the level of the defect: left to right shunt along the pressure gradient. As LA- RA pressure gradient is not significant,
the shunt is not turbulent enough to produce a murmur
Level Hemodynamics
RA Volume overload------ RA dilation----- Dysfunction and failure
RV 1.Volume overload------ RV dilation----- Dysfunction and failure
Pulmonary valve 1.Functional PS (due to abnormal blood flow through a normal valve).
2.Delayed closure of pulmonary valve as RV systolic ejection time get prolonged
leading to a delayed P2
Pulmonary artery PAH
LA LA volume overload and dilation may occur after a long time.
As LA – RA pressure gradient is not significant so Right sided overloading Effects take long time before it becomes
symptomatic
 Often Asymptomatic, diagnosed incidentally as Right sided “overloading effects “ often does not develop in
ones’ life time
 RHF Swelling may occur in late stages of ASD as a result of RHF.
Signs:
 S1: Normal
 S2: Usually normal in intensity, P2 may be loud if PAH develops
 Split: wide but fixed split
 Murmur: Mid systolic murmur over pulmonary area due to: Functional PS (due to abnormal blood flow
through a normal Pulmonary valve).
Mechanism of physiological splitting in second heart sound (during inspiration):
 During inspiration, a negative intrathoracic pressure is created

 This creates a “suction” effect which results in increased venous return to the right side of the heart.
 Hence the RV ejection time gets prolonged during inspiration.
 Also Pulmonary vascular bed expands in capacity, so it “holds back” some amount of blood & consequently
amount of blood flowing from KLungs to LA decreases.
 Hence the LV RV ejection time gets shortened during inspration
Because of these 2 factors, AV closes before that of the PV and the split is appreciated during inspiration
Mechanism of wide and fixed split in ASD:
 The split is wide because RA is dealing with extra amount of blood (in addition to the normal venous return, it
receives blood from LA) and this extra blood is received by RV, RV systolic ejection time gets prolonged and
consequently there is a delayed occurrence of P2.
 The split is fixed because:
 During inspiration, venous return increases through vena cava and so, RA receives more amount of blood. So,
amount of L-R shunt decreases.
 During expiration, capacity of pulmonary vasculature decreases and more amount blood flows into LA. So,
amount of L-R shunt increases.
 So, venous return and L-R shunt varies reciprocally during inspiration and expiration; resulting in a fixed
split.
Investigation: Echocardiogram confirms the diagnosis/type/severity of ASD
Treatment: 1. Management of heart failure 2. Surgical correction of defect
Patent ductus arteriosus (PDA)
PDA is non obliteration of ductus arteriosus (which is a communicating vessel between aorta and pulmonary artery
and usually obliterates by the time one is born.
Hemodynamics:
Hemodynamics at different levels:

Through PDA: continuous Left to right shunt as Aortic Systolic as well as Diastolic pressure is much higher than that
of Pulmonary artery
Pulmonary artery: Volume overloadleading to PAH
RV/RA: pressure overload may occur from PAH at late stage
- Both of which may result in RHF at a late stage.
 Often Asymptomatic.
 symptoms of RHF at a late stage: Edema
Signs:
 A continuous machinery murmur continuing throughout the systole and diastole is usually present over the
pulmonary area.
 As PA pressure rises and shunt eventually reduces (which may occur after a long time), both the components
of the murmur (particularly the diastolic component) becomes less intense.
Investigation: Echocardiogram confirms the diagnosis
Treatment:
1. Surgical correction of defect
2. Obliteration of ductus arteriosus can be induced by Indomethacin
3. Symptomatic management of HF, if present.
Coarctation/ stenosis of aorta
Segmental narrowing of aorta usually between arch of aorta and descending thoracic aorta
This condition is sometimes associated with: ● Aneurysm of circle of Willis ● Mitral valve prolapse
Hemodynamics:
 Pre-stenotic part (blood flows to the upper part of the body): there is high Pressure
 At the post-stenotic part (blood flows to the lower part of the body), there is low Pressure
 The pulse volume may be slightly weaker at the lower extremity while compared to upper extremity.
Symptoms:
Asymptomatic.
BP high related manifestations & its complications: COA is one of the causes of Hypertension in young individuals
Signs:
1. Asymmetry of radial and femoral pulse volume with radio-femoral delay
2. Brachial artery BP disproportionately higher than femoral artery BP
3. Visible, pulsatile collaterals may be present over the chest wall (Suzman’s sign).
4. Rarely, a systolic bruit can be heard over the interscapular area.
Investigation: ● Echocardiogram confirms the diagnosis ● CT Aortogram scan for better visualization
Treatment: ● Surgical correction of coarctation ● Symptomatic treatment for hypertensive complications
Pheochromocytoma
Catecholamine-secreting tumor that may precipitate life-threatening hypertension.
Classically associated with 3 syndromes—
●Von Hippel-Lindau syndrome ● Multiple endocrine neoplasia type 2 (MEN 2) ● Neurofibromatosis type 1 (NF1)
Signs and symptoms
Classically, pheochromocytoma manifests as spells with the following 4 characteristics:
Headaches Diaphoresis
Palpitations Severe hypertension
Typical patterns of the spells are as follows:
Frequency may vary from monthly to several times per day
Duration may vary from seconds to hours
Over time, spells tend to occur more frequently and become more severe as the tumor grows
Signs: Hypertension: Paroxysmal in 50% of cases

Investigation: Diagnostic tests for pheochromocytoma include the following:
Plasma metanephrine level: high
24-hour urinary collection for catecholamines and metanephrines: high
Imaging studies should be performed only after biochemical studies have confirmed the diagnosis.
Abdominal CT
MRI: Preferred over CT scanning in children and pregnant or lactating women
PET scan: A promising technique for detection and localization of pheochromocytomas
Management
Surgical resection of the tumor is the treatment of choice and usually cures the hypertension. Careful preoperative
treatment with alpha and beta blockers is required to control blood pressure and prevent intraoperative hypertensive
crisis.
Preoperative medical stabilization is provided as follows:
Start alpha blockade with Phenoxybenzamine 7-10 days preoperatively
Provide volume expansion with isotonic NaCl
Initiate a beta blocker only after adequate alpha blockade, to avoid precipitating a hypertensive crisis from unopposed
alpha stimulation
Pulse: Special/ abnormal character..(Hahahahaha!!!)
Anacrotic Pulse: slow rising, twice beating pulse where both the waves are felt during systole.
Cause: Aortic stenosis
Pulsus Bisferiens: Rapid rising, twice beating pulse where both the waves are felt during systole.
Causes:
Idiopathic Hypertrophic subaortic stenosis/HOCM
Combined Aortic valve disease: Severe AR with mild AS
Pulsus Parvus et Tardus: slow rising pulse like the anacrotic pulse but the anacrotic wave is not felt.
Cause: Aortic stenosis.
Pulsus Alternans: strong and weak beat occurring alternately, probably due to alternate rather than regular
contraction of the muscle fibres of the left ventricle.
Causes: 1. LVF 2. Toxic myocarditis 3.Paroxysmal tachycardias
Pulsus Paradoxus: Systolic blood pressure normally falls by 3-10 mm. during inspiration because though there is
increased venous return to the right side of the heart, left sided filling and hence stroke volume decreases there is
relative pooling of the blood in the pulmonary vasculature as a result of lung expansion and more negative
intrathoracic pressure during inspiration.
This decreases the venous return to the left atrium and ventricle and subsequently causes a fall in left ventricular
output decreasing the arterial pressure.
When the systolic blood pressure falls more than 10 mm. Hg. During inspiration the pulse is “erroneously” called
pulsus paradoxus although it merely is an exaggeration and not a reversal of the normal.
The paradox is that in extreme cases the peripheral pulse can disappear on inspiration while, paradoxically, heart
sounds remain audible during the “missed beats”.
Causes:
Superior vena cava obstruction
Lung: Acute exacerbation of asthma/ COPD
Cardiac: Tamponade/ constrictive pericarditis and severe congestive cardiac failure
Pulsus Bigeminus: coupling of the pulse waves in pair, followed by a pause. It is seen in alternate premature beats,
A.V. block, and sinoatrial block with ventricular escapeThready Pulse: pulse rate is rapid and the pulse wave is
small and disappears quickly. This is seen in shock especially cardiogenic.
Waterhammer Pulse: Large bounding pulse (ie high volume) associated with increased stroke volume of the left
ventricle and decrease in the peripheral resistance, leading to a wide pulse pressure.
The pulse strikes the palpating finger with a rapid, forceful jerk and quickly disappears. It is best felt in the radial
artery with the patient’s arm elevated.
Pathophysiology:
High volume because: Increased stroke volume of the left ventricle
Rapid collapse: decrease in the peripheral resistance as “arterial arcade” suddenly “empties” due to rapid diastolic run
off of blood: in backward direction (Aorta to LV) in AR because of incompetent valve or in forward direction as in
other causes due to rapid vasodilatation.
Causes:
Aortic regurgitation Endocrinopathy: Thyrotoxicosis
Beri beri Fever
Cirrhosis Gestation
Ductus arteriosus: PDA
Central Nervous
System
Upper and lower motor neuron (UMN and LMN)
Motor function = Movement of any body part = contraction of muscle(s)
Motor neuron= Nerve cells forming part of a pathway along which impulses pass from the brain or spinal cord to a
muscle:
2 parts:
Upper motor neuron: “Guardian”/”supervises” LMN: Multiple descending fibres (motor pathways) with excitatory as
well as inhibitory effects on LMN circuit
Anatomically: These are 2 main groups of nerve fibres coming down from the cerebral cortex:
1. Corticospinal fibres innervating Anterior horn cell These 2 pathway are called
2. Corticonuclear fibres innervating Motor Cranial nerve nuclei ‘upper motor neurons’
Lower Motor Neuron: “Final common pathway” carrying impulses to the“effector “ i.e Muscles
LMN acitivity is influenced by
1. Sensory feedback form muscles & tendons
2. Excitatory and inhibitory effects of UMN
Anatomically:
Spinally innervated muscles: Anterior horn cell onwards pathway up to Myoneural junction ‘lower
Cranially innervated muscles: Motor Cr. Nerve Nucleus onwards pathway up to Myoneural motor neurons’
Feature of UMN and LMN lesions:

 UMN lesion: Loss of voluntary movement
 LMN lesion: Paralysis of muscle Let’s not go into the details of “why” UMN & LMN lesions show 2
different pattern/ characters!!
Features of UMN and LMN lesions:
Points UMN lesion LMN lesion
Muscle power Decreased: Weakness
Therefore “Weakness” DOES NOT help to establish whether it is UMN or LMN
lesion- FOLLOWING pattern of signs help us to establish
Muscle tone Hypertonia/ spasticity Hypotonia/ flaccidity
Wasting/ atrophy of muscles Absent Present( but takes time to develop)
Deep tendon reflex (DTR)/ Jerk Exaggerated (clonus may be present) Absent
Superficial reflex Plantar: Extensor Plantar: Never extensor
Other superficial reflexes: Lost Other superficial reflexes: Lost
Fasciculation Never May be present (Certain chronic
degenerative diseases of Anterior horn
cell or Motor Cr. Nve nuclei
Above signs will be present in that part of the body which is innervated by the affected/ damaged UMN/LMN
Shock stage: After a sudden/an Acute UMN lesion although LMN is structurally intact it becomes functionally
incompetent temporarily, during this period the affected part of the body shows LMN pattern of the signs- Flaccidity
+ areflexia (Loss of Deep tendon reflexes/jerks) but Planter usually remains EXTENSOR even during this period. This
stage is called Shock stage of UMN lesion and may persist for few days to few weeks.
Points Shock stage of UMN lesion LMN lesion

Muscle power Decreased: Weakness
Muscle tone Hypotonia/ flaccidity Hypotonia/ flaccidity
Wasting/ atrophy of muscles Absent Present( but takes time to develop)
Deep tendon reflex (DTR)/ Jerk Absent Absent
Superficial reflex Plantar: Extensor Plantar: Never extensor
Other superficial reflexes: Lost Other superficial reflexes: Lost
Therefore PLANTAR is the MOST IMPORTANT (and often THE ONLY) point to diagnose an UMN/LMN lesion
WHERE do we get above 2 patterns of signs
Weak muscles/Weak areas show these signs
BUT Which is the “weak area”??
Lower Motor Neuron lesion Upper Motor Neuron lesion
ONLY the Area served by the All the areas whose Lower motor has
affected LMN lost Upper Motor neuron connectiom
Area served by a particular LMN These are the LMNs who are yet to be
is called “Myotome” of that LMN innervated by their UMN
Therefore “at the level” of the lesion Therefore “below the level” of the lesion
Brain lesion vs Cord lesion

effects will be seen
contralateral ipsilateral
to the side of lesion
Corticospinal fibres (CST)

Course
So, if corticospinal tract is

damaged in the brain, effect
will be seen contralateral to
the side of lesion.
If corticospinal tract is
damaged within the spinal
cord, effect will be seen
ipsilateral to the side of
lesion
Corticonuclear fibres (CNT)
Corticonulear fibres to 7th nerve nucleus
Course
They arise from cortex and ultimately innervate different motor cranial nerve nuclei in the brainstem, forming UMN
pathway of that particular cranial nerve.
 Therefore, all of the motor cranial nerve nuclei are bilaterally innervated by corticonuclear fibres (except lower half
of 7th cranial nerve nucleus).
 CN7 nucleus has an upper ½ and a lower ½ from which, upper and lower ½ of facial muscles are innervated.
 Corticonuclear fibres of the upper ½ of the CN7 nucleus are exactly like the other motor cranial nerve nuclei.
Therefore, upper ½ of CN7 nucleus is receive corticonuclear fibres from both hemispheres.
 But, corticonuclear fibres destined for lower ½ of CN7 nucleus decussate to innervate the nuclei of the contralateral
side.
 Therefore, lower ½ of CN7 nucleus gets unilateral corticonuclear innervation which comes from contralateral side.
Brain lesion/disease
lesion at an area through which

Brain lesion CST/CNT don’t pass
No Corticospinal(CST)/ Corticonuclear(CNT) damage No hemiplegia!!
lesion at an area through which
CST/CNT pass but CST/CNT spared
CST/CNT damaged: then also it can be
Corticospinal fibres damaged and/ or Corticonuclear fibre damaged
Contralateral UL and/or Contralateral LL limb weakness and/or Contralateral lower half of face weakness
(UL/LL will show UMN pattern of signs)
Therefore a Brain disease if DAMAGES corticospinal/Corticonuclear pathway the effects will be similar
irrespective of the site or level of the lesion & the effect is Contralateral UL weakness and/or Contralateral LL limb
weakness (with UL/LL showing UMN pattern of signs)and/or Contralateral lower half of face weakness
So a brain disease if DAMAGES CST/CNT overall effect can be of following types
1. Contralateral Upper limb weakness only with UMN pattern of signs Monoparesis
2. Contralateral Lower limb weakness only with UMN pattern of signs
3. Contralateral Upper limb & Lower limb weakness with UMN pattern of signs: Hemiparesis
4. Contralateral lower half of face weakness only: Facial involvement ONLY. No limb involvement
5. Contralateral Upper limb &/or Lower limb weakness with UMN pattern of signs Mono/Hemiparesis
With Contralateral lower half of face weakness with Facial weakness
Therefore above features will not be able to tell us the site or level of lesion. Site/level of lesion can be predicted by
looking at the features that accompany above features because ACCOMPANYING features are due to damage of the
structures present at different areas of the brain which are present along with CST/CNT and these structures are
different at diffrent sites through which CST/CNT descends.
So to understand the level of LESION of CST/CNT we need to know who are the structures that accompany them at
different areas of the brain.
However we must UNDERSTAND that if a lesion occurs in ANY of these areas the lesion can damage ANY 1 or
MORE than 1 of these structures. So clinical presentation of the patient will be variable.
Localization of site/ level of Corticospinal tract lesion
Site Structure vulnerable to get Effect
damaged
CST and/or CNT innervating Contralateral UL and/or LL and/or Contralateral lower ½ of face
Cortex lower ½ of 7th nerve nucleus weakness (UMN type 7th palsy)
Higher cortical areas Higher cortical dysfunction (eg: speech area damage: aphasia)
Fibres of visual field Visual field defect
Internal CST and/or CNT innervating Contralateral UL and/or LL and/or Contralateral lower ½ of face
capsule lower ½ of 7th nerve nucleus weakness (UMN type 7th palsy)
Midbrain CST and/or CNT innervating Contralateral UL and/or LL and/or Contralateral lower ½ of face
lower ½ of 7th nerve nucleus weakness (UMN type 7th palsy)
3rd nerve nucleus Ipsilateral LMN type 3rd nerve palsy
4th nerve nucleus Ipsilateral LMN type 4th nerve palsy
Pons Corticospinal tract Contralateral UL and/or LL weakness
7th nerve nucleus Ipsilateral LMN 7th Nv. palsy(whole face weak: both lower and upper
part)
CN6th nerve nucleus Ipsilateral LMN type 6th nerve palsy
5th Neve Motor Nucleus Ipsilateral LMN type 5th nerve palsy
Principal sensory nucleus 5th Loss of touch sensation from ipsilateral ½ of face
Nve.
Sympathetic trunk Ipsilateral Horner’s syndrome
Lateral spinothalamic tract Loss of pain and temperature sensation from contralateral ½ of body
Medulla Corticospinal tract Contralateral UL and/or LL weakness
10th,11th,12th nerve nucleus Ipsilateral LMN type 10-12th nerve palsy
9th nerve nucleus Ipsilateral 9th nerve palsy(sensory nerve: so “LMN” not applicable)
Sympathetic trunk Ipsilateral Horner’s syndrome
Lateral spinothalamic tract Loss of pain and temperature sensation from contralateral ½ of body
Spinal nucleus of CN5 Loss of pain and temperature sensation from ipsilateral ½ of face
Let’s recapitulate!!!
A lesion in ANY of these areas can damage ANY 1 or MORE than 1 of the above structures. So clinical presentation
of the patient will be variable.
As CST and CNT are descending through these areas they often get damaged BUT will not be damaged
ALWAYS!!...So a patient can come without Hemiplegia!!!
Cerebellar manifestations
A: Ataxia: gross incoordination of muscle movements. The patient may be very unsteady on their feet towards the side of
the lesion
B: Broad, coarse tremor that typically worsens as an extremity approaches the endpoint of deliberate and visually guided
movement (hence the name intention tremor)
C: Co-ordination lack
D:
Dysdiadokinesia: inability to perform a series of rapidly alternating muscle movements (typically flipping one hand rapidly
on the palm of the other)
Dysmetria: lack of coordination of movement typified by the undershoot or overshoot of intended position with the hand
E: Eye: Nystagmus
F: Floppy (Hypotonic) Muscles: Not important
Spinal cord
Myelopathy
Diseases affecting spinal cord.
Types:
Acute
ALL the structures within the cord are vulnerable to get damaged
Compressive
No “selection bias”
Myelopathy Chronic
Non-
Acute
compressive These diseases have structure predilection
Chronic “Structure selection bias”
Myelopathy
Structures vulnerable to get damaged in myelopathy:
1. Anterior horn cell (AHC) Motor function controlling structures
2. Corticospinal tract (CST)
3. Lateral Spinothalamic tract fibres

4. Dorsal column fibres Sensory function controlling structures
5. Dorsal root
6. Sphincteric centres or higher cortical Fibres controlling sphincteric centre
Therefore Myelopathy often presents with triad of

1. Motor manifestations: Weakness of body parts
2. Sensory manifestations: Sensory impairment
3. Sphincteric manifestations: Urinary/fecal incontinence
Compressive myelopathy: Because ALL the structures within the cord are vulnerable to get damaged so we get a
“pattern” of manifestations but No such pattern in Non compressive myelopathy as each disease behave
differently
Compressive myelopathy
Anterior horn cell (AHC): Forming LMN pathway for it’s myotome
Corticospinal tract (CST): Innervating AHC of each segment as firbes descend
through the cord
Therefore AHC of each segment contains “circuit for it’s area ONLY”, so controls a
particular myotome
But
CST present at each segment contains UMN fibres for all those AHCs who are yet
to be innervated and therefore “UMN circuit for ALL the myotomes” innervated by
AHCs/LMN below that segment influences
Distribution of Motor manifestations:
Structures damaged: “Geography” or which areas/parts of the body get affected
Anterior horn cell: Ipsilateral Myotome of the affected segment (“at the level of the lesion”): LMN pattern signs
Corticospinal fibre: Ipsilateral myotomes of ALL the segments below the compressed segments (“below the level
of the lesion”): UMN pattern of signs
Distribution of Sensory manifestations:
Dorsal root: In the dermatome of the affected segment: Loss of ALL types of sensation
Dorsal column: In the dermatomes of ALL the segments below the affected segment: Loss of deep sensation
Lateral Spinothalamic fibres: In the dermatomes of ALL the segments below the affected segment: Loss pain & temp
sensation
Symptoms:
1. Motor: Weakness/paralysis: Quadriparesis or Paraparesis depending on the level of compression
2. Sensory:
a. Impairment/ loss of sensation: Often patient complain of a definite upper level/ border below which sensations
are impaired. This upper border varies according to the level of compression[
b. Root pain (Radiculopathic pain):due to irritation/ compression of nerve root
 Site: In the dermatome of the compressed root
 Character: Often severe, deep seated pain, may be aggravated with movements, coughing, sneezing.
3. Sphincteric disturbances: 1. Bowel dysfunction: Incontinence 2. Bladder dysfunction: Retention/ incontinence.
Signs: are present BILATERALLY often they are bilaterally asymmetrical
Complete cord compression/ transection
Corticospinal fibres
 At the level of compression:

1. Weakness with Bilateral LMN pattern of signs: Bilaterally (due to damage to AHC)
2. Impairment of all sensations due to compression of dorsal root/ sensory fibres entering through it.
 Below the level of compression:
1. Weakness with UMN pattern of signs: Bilaterally I
2. Impairment of all sensory modalities (superficial and deep) bilaterally.
Therefore upper level of sensory impairment corresponds to the dermatome of compressed segment.
Partial/ incomplete cord compression/ hemisection of spinal cord
 At the level of compression:

1. Ipsilateral LMN sign (due to damage to AHC)
2. Impairment of all sensations in the dermatome of compressed segment: Ipsilateral (damage to dorsal root).
 Below the level of compression:
1. Ipsilateral UMN signs (due to damage to ipsilateral CST)
2. Ipsilateral side: Impairment of deep sensation
3. Contralateral side: Impaired pain and temperature sensation (due to damage of LSTT)
Localization of lesion
Motor manifestations Sensory manifestations Cord segment compressed
Upper limb: Weakness with Upper border/level of sensory loss Cervical cord
combined UMN and LMN signs somewhere in the upper limb As the level of compression goes down in
++ Cervical cord more and more part of Upper
Lower limb: Weakness with limb remains Neurologically intact
combined UMN and LMN signs
Thoracic cord
As the level of compression goes down in
Upper limb: No Weakness Thoracic cord the upper border of sensory
++ Upper border/level of sensory loss shifts towards the ABDOMEN
Lower limb: Weakness with loss somewhere in the trunk So,
UMN signs Upper thoracic compression: upper border
of sensory loss towards CHEST
Lower thoracic compression: upper border
of sensory loss towards ABDOMEN
Upper limb: No Weakness Upper border/level of sensory loss Lumbo sacral cord
++ somewhere in the Lower limb As the level of compression goes down in
Lower limb: Weakness with L-S cord more and more part of lower limb
combined UMN and LMN signs remains Neurologically intact
General topics
Higher function
Speech: Dysphasia/Aphasia: 2 types: a. Wernicke’s b. Broca’s
Features Broca’s aphasia Wernicke’s aphasia
Description Due to lesion of inf.frontal gyrus (supplied Due to lesion of sup. temporal gyrus (supplied by
by sup.division of MCA inf.division of MCA)
Comprehension Intact Impaired

Expression  Impaired  Voluminous
 Word finding difficulty  Contains little information
 Non-fluent aphasia/ telegraphic speech.  Fluent aphasia/ Jargon speech
Tone of muscles
Hypertonia/ Rigidity
1. Clasp knife type (UMN lesion)
2. Parkinsonism
• Lead pipe type (uniform; rigidity > tremor)
• Cogwheel type (interrupted, tremor> rigidity)
Hypotonia/ Flaccidity
1. Shock stage of UMN lesion
2. LMN lesion (same segment)
Power of muscles
Power Description
0 No movement
1 Flicker of movement
2 Unable to move against gravity
3 Movement possible against gravity but not against resistance
4 Movement possible against resistance but with some weakness
5 Normal power
Reflex/ Deep tendon reflex (DTR)
Reflex Spinal level Peripheral nerve
Biceps jerk C5-C6 Musculocutaneous nerve
Supinator jerk C5-C6 Radial nerve
Triceps jerk C6-C7 Radial nerve
Finger flexion jerk C7-C8 Median and ulnar nerve
Knee jerk L2, L3, L4 Femoral nerve
Ankle jerk L5, S1 Sciatic nerve
Abnormality of deep tendon reflexes:

1. Brisk/ exaggerated:
Cause:
UMN lesion: Below the level of lesion- all reflexes will be brisk.
Non-neurological: anxiety/ thyrotoxicosis
2. Clonus: It is the external manifestation of an exaggerated DTR characterized by rhythmical repeated contraction of
a muscle in response to sudden sustained stretching of its tendon, leading to oscillatory movement of a part of the body. It
is best seen in the knee (patellar clonus) and in the ankle (ankle clonus).
Features Pseudo-clonus/ Physiological clonus True-clonus/ Pathological clonus
Extension Ill sustained (<5-6) Well sustained (≥7)
Signs of UMN lesion Absent Present
Cause Anxiety UMN lesion
3. Absent deep reflex:
Causes:
 LMN lesion: Reflex(es) mediated by the particular damaged LMN pathway will be lost
 Spinal shock stage of UMN lesion
Jendrassik’s Maneuver: It is a special maneuver performed while examining DTR when they seem to be absent/
diminished. It must be performed before concluding that the jerk is absent.
In case of upper limb jerks, the patient is asked to clench his teeth tightly.
In case of lower limb jerks, the patient is asked to hold his fingers tightly with each other and suddenly pull them up
against each other.
Tapping of the tendon should coincide with this maneuver.
 Mechanism: This maneuver increases the excitability of reflex response by:
a. By increasing the excitability of AHC
b. By increasing the recruitment of γ-fusiform fibres of the muscle spindle.
Superficial reflex
Reflex Spinal level
Abdominal reflex T7-T12
Cremasteric reflex L1-L2
Plantar reflex S1
Anal reflex S2-S4
Bulbocavernosus reflex
Loss of superficial reflex:
 In UMN lesion: Below the level of lesion
 In LMN lesion: At the level of lesion
Plantar reflex
Normal response: “Flexor”
1. Plantar flexion of the great toe
2. Plantar flexion and adduction of the other toes
3. Contraction of tensor fascia lata.
Why the lateral aspect of the sole is stroke?

 The reflexogenic area of the plantar reflex lies on the lateral aspect of sole
 If the medial aspect of sole is stroke, plantar reflex occurs due to grasp response.
Why the ball of the great toe shouldn’t be stroked?

If it is stroke, due to direct stimulation of muscle fibres; dorsiflexion of toe occurs giving an erroneous interpretation of
extensor plantar.
Abnormality of plantar response:
Extensor plantar/ Babinski’s sign/ Upgoing plantar
1. Dorsiflexion of great toe: THE MOST IMPORTANT COMPONENT
2. Dorsiflexion and fanning out of the other toes
3. Triple flexion: Dorsiflexion at ankle + Flexion at knee + Flexion at hip.
Causes of Extensor plantar:

1. Structural damage of corticospinal/ pyramidal tract (usually bilateral extensor is seen)
2. Functional impairment of corticospinal tract:
a. Newborn infant
b. Any cause of deep unconsciousness/ coma
c. Post-ictal stage.
Absence of plantar response:

1. LMN lesion of S1 segment
2. Thick sole
3. Anesthesia of sole.
Withdrawal response: When the entire limb is withdrawn from nociceptive stimulation (usually occurs when patient
is very sensitive to touch/ the sole is stroke forcefully).
Equivocal response: Incomplete response. This is considered to be a part of extensor plantar response.
Plantar equivalent:
In some patients with UMN lesion, the reflexogenic area of plantar reflex widens; leading to extensor plantar response
when different parts of the lower limb are stimulated. Ex:
 Gordon’s sign: When the calf muscle (Gastrocnemius) is squeezed For “Final MBs”!!
 Chaddock’s sign: When the lateral malleolus is stroke in semicircular pattern
 Oppenheim's sign: When pressure is applied over the medial side of tibia in a downward direction.
Causes of extensor plantar with absent ankle and knee jerk

1. Spinal shock stage of UMN lesion
2. Compressive myelopathy where compression occurs in the fragment controlling the above jerk (S1)
3. Other uncommon causes: 1. Subacute combined degeneration of spinal cord 2. Fredrick’s ataxia 3. Tabes dorsalis.
Muscle atrophy (Wasting)

Causes:
1. LMN lesion: at the level of lesion
2. Myopathy
Cranial nerves
CN1: Olfactory
Olfactory pathway
Odorant Receptor Olfactory filament Olfactory bulb( cribriform plate) Olfactroy cortex
Hyposmia/ Anosmia:
1. Transport defect: DNS/ Polyp/ Rhinitis 3. Neural defect:
2. Receptor defect: Viral infection Trauma/ fracture of cribriform plate
Tumor: Meningioma of olfactory groove
CN2: Optic Nerve
Alzheimer’s disease
Kalmann’s syndrome (anosmia + hypogonadism)
CN 2: Optic Nerve
Functions of the optic nerve: 1. Visual acuity 2. Color vision 3. Visual field
(White: Lost field of

vision)
Post chiasmal
Pregeniculate/ Optic tract
Post geniculate/ Optic radiation
(White: Lost field of vision)

Lesions at different levels and their effects
Level of lesion Effect
Optic nerve Monocular loss of vision from both the fields of the affected side
In the affected eye: Light reflex (LR): Absent
Causes: 1. Optic neuritis 2. Optic nerve tumor 3. Graves’ Opthalmopathy
Optic chiasma Bitemporal hemianopia (both temporal fields are lost)
Causes: 1. Pituitary tumor(Macroadenoma) 2. Craniopharyngioma
Post chiasmal lesion Optic tract & optic radiation lesion: crossed/ contralateral Homonymous hemianopia
1. Pregeniculate/ Homonymous: Identical sided half of the visual field of each eye is lost
Optic tract Crossed/ Contralateral: as the visual field affected is the one contralateral to the side of the
2. Post geniculate/ lesion
Optic radiation Causes: 1.Stroke 2.Tumor 3.Demyelniating disease
Optic tract 1.Light reflex: lost when light is thrown from a particular direction but present when light
is thrown from another direction: Wernicke’s Hemianopic pupil
2.Hemianopia: Congruous in type: fibres within optic tract are densely arranged; when the
visual field loss is mapped out in Perimetry, they look symmetrical/ identical
Optic radiation 1.Light reflex: Intact
2. Incongruous in type (The fibres within optic radiation are widely separated, when the
visual field loss is mapped out in Perimetry, they look asymmetrical
Light reflex
Pathway of light reflex
From Pretectal nucleus fibres go to Ipsilateral +
Contralateral EWN: Hence Ipsialteral(Dircet LR) as
well as Contralateral (Consensual LR) Pupil
constricts when Light is thrown to either eye
Parasympathetic fibres (which constricts pupil) pass

along CN3 fibres and therefore, often damaged in
CN3 nerve lesions.
Loss of light reflex

Causes:
1. Optic nerve lesion
2. Optic tract lesion (pre-geniculate lesion):
The affected eye in this case is called “Wernicke’s hemianopic pupil”: LR is lost in this eye when light is thrown
from a PARTICULAR direction/side, but DLR is present when light is thrown from ANOTHER direction/side
3. CN3 palsy: “Surgical” Causes (“Medical” Causes: Pupil spared)
Argyll Robertson Pupil (SN)

It is an abnormality of pupil usually seen in patients of neurosyphilis.
Usually bilateral Pupil is small in size and dilates poorly to mydriatics
Light reflex is lost but Accommodation Reaction: Present (Remember: ARP in ARP).
Accommodation reaction
Components:
1. Medial convergence of eyeball
2. Pupillary constriction
3. Anterior-posterior bulging of lens
Loss of accommodation reaction: CN3 palsy (as CN3 supplies both medial rectus and constrictor pupillae)
CN3, CN4 and CN6
Function: Innervate extraocular muscles and thereby mediate movement of eyeball.
Innervation of EOM:
[ALL+ 1] 3 [SO] 4 [LR] 6“
+ 1” = Elevator of the upper eye lid: Levator Palpebrae Superiorirs
(Other Elevator: Mullers Muscle: Sympathetic innevation)
3rd/4th/6th Nerve Lesion

Causes of CN3 and/or CN4 and/or CN6 palsy
Anatomical site of lesion Cause
Diseases of midbrain  CVA
 Tumor
 Demyelination
Meningeal diseases Basal Meningitis: In meningitis, the inflammatory exudate often “strangulates”
the nerve at the basal meninges.
Diseases of  Cavernous sinus thrombosis
Cavernous sinus  Carotid-cavernous fistula
Superior Orbital Fissure/  Tumor
Retro-orbital diseases  Trauma/ Orbital Fracture
 Graves’ Opthalmopathy
Peripheral fibres Mononeuritis multiplex (secondary to diabetes and vasculitis)
CN6 palsy & Raised ICT: As CN6 has the longest intracranial course, fibres often get stretched when ICT raises;
Symptoms and sign of palsy

Symptoms
1. Diplopia: Maximum when the patient tries to look towards the direction to which the affected(weak) muscle(s)
would have turned the eyeball to.
2. Ptosis: Drooping of the upper eyelid (in 3 rd nerve lesion/palsy)
Signs
1. Extraocular muscle weakness: Which muscle(s) get(s)Weak: depend on the nerve damaged/ lesion
(what we, doctors see!!): Eyeball does not move towards the direction to which the affected(weak) muscle(s) would
have turned the eyeball to.
2.Light reflex: Lost: in SOME CASES of 3rd nerve lesion: “Compressive /Surgical Causes”
3.Accommodation reflex: Lost
Diplopia
3 and/or 4 and/or 6 nerve lesion
rd th th No nerve lesion
Nuclear/Infranuclear lesion MNJ disease Ocular myopathy
Myasthenia Gravis Graves’ disease

Ptosis (Drooping of upper eyelid)
Causes of ptosis
3 rd nerve palsy Sympathetic trunk damage Myasthenia Myotonic dystrophy

(Nuclear/Infranuclear lesion Horner's syndrome gravis Ocular myopathy
Diplopia++ No diplopia Diplopia++ No diplopia
Pupil: big+ No LR Pupil: Small Pupil: Normal Pupil: Normal
Clinical features according to the causes of ptosis

CN3 palsy Horner’s syndrome Myasthenia gravis
Complete ptosis Partial ptosis/ pseudo-ptosis Fatiguable ptosis
Diplopia+ EOM weakness++ Non-fatiguable Diplopia+ EOM weakness++
(Non-fatiguable) (fatiguable)
Usually unilateral Usually unilateral Usually bilateral
Pupil: Large Pupil: Small Pupil: Normal
Other signs of CN3 palsy are Other features of Horner’s Fatigable weakness of other
present syndrome are present muscles elsewhere may be present
Squint: Brief discussion

Squint is of 2 types, the features of which are being discussed in brief:
Non-paralytic Paralytic
Present since birth Usually develops later
No diplopia Diplopia present
Movement of eyeball not restricted Movement of eyeball restricted
(as there is NO weakness of EOM)
No signs of cranial nerve palsy Signs of cranial nerve palsy present
CN5
Functions/Fibres:
Motor function: Innervates masticatory muscles:
a. Masseter
b. Pterygoid.
c. Temporalis
Sensory function: superficial sensation from ipsilateral half of face
a. Ophthalmic
b. Maxillary
c. Mandibular.
Reflex: mediates the following reflexes:
a. Corneal reflex
b. Jaw jerk.
Corneal reflex pathway Loss of corneal reflex
Causes:
1. Deep coma
2. CN5 palsy (damage to ophthalmic division):
3. CN7 palsy:
4. Death!!!.
Features of CN5 palsy

1. Motor dysfunction:
a. Weakness of masticatory muscles leading to difficulty in mastication
b. Wasting of temporalis and masseter, leading to hollowing of the face.
2. Sensory dysfunction:
Loss/ impairment of sensation from ipsilateral half of face.
In many cases, only one sensory branch of trigeminal nerve gets damaged, leading to sensory impairment
from the distribution of the affected branch only.
3. Loss of corneal reflex.
Causes of CN5 palsy

1. Brainstem lesion: 1. CVA 2. Tumor 3.Demyelination
a. Pontine lesion:
 Motor paralysis
 Touch sensation lost from ipsilateral half of the face (Principal sensory nucleus is in the pons)
b. Medullary lesion: Pain & Temperature: lost from ipsilateral half of the face (Spinal nucleus is in the medulla)
2. Posterior fossa lesion: CP angle tumor (Acoustic neuroma)
3. Trigeminal ganglion lesion: 1.Tumor 2.Trauma 3.Gradenigo’s syndrome
4. Cavernous sinus pathology: Thrombosis (Only affects Opthalmic division of the Nerve)
Trigeminal neuralgia (SN)

It is a condition characterized by excruciating pain along the distribution of trigeminal nerve.
Etiology
1. Idiopathic
2. Multiple sclerosis
3. Intracranial space occupying lesion (IC-SOL): Tumor stretches the nerve fibres
Clinical features
Pain:
a. Site: Usually hemifacial pain, particularly in the chick and chin
b. Nature: Severe, often electric shock like pain and typically paroxysmal
c. Triggering factor: Often triggered by face washing, shaving, chewing
d. The pain is so severe that it causes severe facial spasm and the patient involuntarily starts wincing like a tic; therefore
the condition is also called Tic douloureux*.
Investigation: Often not required as it is a clinical diagnosis
Treatment
1. Medical: Carbamazepine/ Oxcarbamazepine
2. Interventional: a. Radiofrequency ablation of trigeminal ganglion
CN7: Facial Nerve
Functions:
Innervates all the muscles of the face except masticatory muscles (muscles of facial expression).
There are 2 other types of fibres which accompany facial nerve almost along its entire course and therefore considered
to be a part of CN7:
a. Secretomotor fibres to (lacrimal + sublingual + submandibular) gland
b. Taste fibre from ant. 2/3rd of the tongue (post 1/3rd: supplied by CN9).
CN7 palsy
It is of 2 types:
UMN type of CN7 palsy LMN type of CN7 palsy
Due to lesions of the corticonuclear fibres innervating Due to nucleus damage/ infra-nuclear lesion
lower ½ of contralateral CN7 nucleus
Lesion is anywhere above pons Lesion is in the pons/ anywhere along the course of CN7
Feature:Weakness/ paralysis of lower ½ of contralateral Feature:Weakness/ paralysis of whole of the ipsilateral
side of face side of face
Features of CN7 palsy
Symptoms:
Deviation of the angle of the mouth Dribbling of saliva/fluid/food through the weak angle of the mouth
Dysarthria Difficulty in closing the eye
Signs:
1. Unable to elevate the eyebrows/Loss of forehead furrowing/ wrinkling
2. Unable to frown Able to do these in UMN lesion
3. Unable to close the eye:
Eyeball is seen to be rolled upwards on attempted closure of eye. This is called ‘Bell’s phenomenon’. Such an eye is at
risk of developing keratitis.
4. Loss of nasolabial fold
5. Drooping of the angle of the mouth to the affected side: saliva dribbles through angle of mouth
6. Angle of mouth is deviated towards healthy site when patient attempts to smile.
Causes of LM type 7th Nerve palsy with causes and localization of lesion
Site of lesion Disease Features
Pons CVA a. Ipsilateral LMN type CN7 palsy
Tumor b. Ipsilateral CN6 palsy
Demyelination c. Contralateral hemiplegia (CST damage)
CP angle Acoustic neuroma a. Ipsilateral LMN type CN7 palsy
b. Ipsilateral sensorineural deafness (CN8 damage)
c. Ipsilateral CN6 palsy
d. Ipsilateral cerebellar signs
e. Loss of Taste: from Ant 2/3rd of tongue & Dry eye
Temporal bone Trauma a. Ipsilateral LMN type CN7 palsy
Tumor b. Loss of Taste sensation from Ant 2/3 rd of tongue
Petrositis (Gradenigo’s syndrome) and Dry eye
c. Hyperacusis (nerve to stapedius)
Geniculate ganglion Herpes zoster Same as temporal bone lesion +
(Ramsay-Hunt Syndr.) Painful herpetic vesicles over external ear and pinna
Stylomastoid foramen Bell’s palsy Ipsilateral LMN type CN7 palsy
Parotid gland TumorSurgery Ipsilateral LMN type CN7 palsy
Peripheral branches GB syndrome Ipsilateral LMN type CN7 palsy
Lyme’s disease
Neurosarcoidosis
Bell’s palsy (SN)
Rapidly developing LMN type of CN7 palsy due to inflammation of the nerve at/near the stylomastoid foramen.
Etiopathogenesis: It has been postulated that the inflammation of nerve is probably triggered out by HSV infection.
Rapidly developing inflammatory exudate strangulates the nerve, leading to palsy. Because there is no permanent
structural damage of the nerve in many cases, there is usually complete functional recovery.
Clinical features
1. Onset: Usually acute/ subacute: develops over few days
2. Often there is H/O a preceding exposure to cold air/ an attack of common cold
3. Clinical features of CN7 palsy.
Investigation: None required as it is a clinical diagnosis.

Treatment
1. Drugs:
A. Systemic corticosteroid: Most effective if given within 24-48 hours of onset of symptoms. Usually a course
of 10-14 days is given.
B. Acyclovir
2. Prevention of exposure keratitis:
A. Protective eyepad
B. Lubricant eye drop/ ointment.
3. Physiotherapy
Complications
1. Incomplete recovery leading to residual palsy
2. Contracture of facial muscles
3. Aberrant regeneration:
a. Fibres originally innervating facial muscles after regeneration innervate lacrimal gland, leading to lacrimation
during eating (gustatory lacrimation/ crocodile tear).
b. Fibres originally innervating orbicularis oculi after regeneration innervate orbicularis oris, leading to involuntary
twitching of angle of mouth during attempted closure of eye.
CN8
CN 9, 10, 11 & 12 (bulbar cranial nerves)

These cranial nerves are also called ‘bulbar cranial nerves’ as the nuclei lies in the bulb (medulla).
Functions:
CN9:
General Sensory: Carries sensation from pharynx, palate, tonsillar region;
Special sense: taste sensation from post. 1/3rd of tongue.
CN10: Innervates muscles of Pharynx, Palate and intrinsic muscles of Larynx. Palato-Glosso-Pharyngo-Laryngo
CN12: Innervates Tongue muscles. Muscles
CN11: Innervates Sternocleidomastoid (rotate the head towards the opposite side) and Trapezius (elevation and
retraction of shoulder.
Reflexes mediated by bulbar cranial nerves:
1. Pharyngeal/ Gag reflex: On stimulating the posterior pharyngeal wall/ palate with a swab stick, there is reflex
contraction of pharyngeal/ palatal muscles, respectively.
Afferent pathway is formed by: CN9 Efferent pathway is formed by: CN10.
Bulbar palsy
Weakness of the muscles innervted by Bulbar Cranial Nerves
Causes & Types
Bulbar palsy
UMN Type/ Pseudobulbar palsy LMN type/ True bulbar palsy
Damage to the Corticobulbar fibres of both side Nucleus damage Infranucleur lesion
Motor neurone disease CVA Jugular Foramen syndrome
Tumor Bulbar poliomyelitis
Demylenation GB syndrome
MND Diptheretic Polyneuritis
Differences between UMN type (pseudobulbar) and LMN type (true) bulbar palsy
Features UMN type (Pseudo) bulbar palsy LMN type (True)bulbar palsy
Symptoms Dysarthria
Dysphagia
Dyspnea
Nasal regurgitation of food
Nasal intonation of voice
Risk of/ Recurrent episodes of aspiration pNeumonia
Signs of bulbar palsy: In UMN type signs are present bilaterally but in LMN type Unilateral or Bilaterally depending
on the disease as some of the diseases cause Unilatertal lesion and some Bilateral lesion
Examination of: UMN type (Pseudo) bulbar palsy LMN type (True)bulbar palsy
Tongue:
1. Wasting No wasting Wasting may be present
2. Fasciculation No fasciculation Fasciculation present
3. Weakness/Deviation Weak Weak.
In unilateral lesion deviates to the diseased side
(Genioglossus “Pushes”)
Palate/Uvula: No lifting of palatal arch & Uvula No lifting of palatal arch & Uvula
Unilateral lesion Uvula deviates to the healthy side
Gag reflex Lost Lost
Jaw jerk Brisk Lost
Other feature Emotionally unstable No such feature
(laughs without any cause)
CN11 palsy
Clinical features
Sternocleidomastoid (SCM): rotates the head towards the opposite side
1. Paralysis/ weakness of SCM: Inability to rotate the head towards the opposite side
2. Wasting of SCM (in LMN type of lesion)
Trapezius: Inability to retract and elevate the shoulder
Spinal cord
Myelopathy
Diseases affecting spinal cord.
Types:
Acute
ALL the structures within the cord are vulnerable to get damaged
Compressive
No “selection bias”
Myelopathy Chronic
Non-
Acute
compressive These diseases have structure predilection
Chronic “Structure selection bias”
Myelopathy
Structures vulnerable to get damaged in myelopathy:
 Anterior horn cell (AHC) Motor function controlling structures
 Corticospinal tract (CST)
 Lateral Spinothalamic tract fibres
 Dorsal column fibres Sensory function controlling structures
 Dorsal root
 Sphincteric centres or higher cortical Fibres controlling sphincteric centre
Therefore Myelopathy often presents with triad of
1. Motor manifestations: Weakness of body parts
2. Sensory manifestations: Sensory impairment
3. Sphincteric manifestations: Urinary/fecal incontinence
Compressive myelopathy: Because ALL the structures within the cord are vulnerable to get damaged so we get a
“pattern” of manifestations but No such pattern in Non compressive myelopathy as each disease behave
differently
Compressive myelopathy
Etiology: Compressive myelopathy
Acute cord compression
Accident: Trauma (Vertebral fracture/ collapse)
Bleeding: Hematomyelia
Bony/Body (vertebral) disease ● “Vertebral pathology” (may be due to different diseases) is the most
Collapse: Pathological fracture: Osteoprotic IMPORTANT “cause” of Cord compression
Disc disease: Prolapsed Intravertebral disc ● Even with “Chronic/Gradual cause the compressive effect MAY come
Chronic cord compression rapidly
Abscess: Paravertebral abscess: TB/pyogenic
Bony/Body (vertebral) disease:
1. Malignancy: 1. Myleoma 2. Vertebral Metastasis: Common “primaries”: Lung/Prostate/Breast
2. Infection: TB spine
Cord tumor: Menigioma/Neurofibroma/Glioma/Ependymoma
Canal disease: spinal cannal stenosis
Degenerative disc disease
Anterior horn cell (AHC): Forming LMN pathway for it’s myotome
Corticospinal tract (CST): Innervating AHC of each segment as firbes descend
through the cord
Therefore AHC of each segment contains “circuit for it’s area ONLY”, so controls a
particular myotome
But
CST present at each segment contains UMN fibres for all those AHCs who are yet
to be innervated and therefore “UMN circuit for ALL the myotomes” innervated by
AHCs/LMN below that segment influences
Distribution of Motor manifestations:

Anterior horn cell: Ipsilateral Myotome of the affected segment (“at the level of the lesion”): LMN pattern signs
Corticospinal fibre: Ipsilateral myotomes of ALL the segments below the compressed segments (“below the level
of the lesion”): UMN pattern of signs
Distribution of Sensory manifestations:
Dorsal root: In the dermatome of the affected segment: Loss of ALL types of sensation
Dorsal column: In the dermatomes of ALL the segments below the affected segment: Loss of deep sensation
Lateral Spinothalamic fibres: In the dermatomes of ALL the segments below the affected segment: Loss pain & temp
sensation
Symptoms:
Motor: Weakness/paralysis: Quadriparesis or Paraparesis depending on the level of compression
Sensory:
 Impairment/ loss of sensation: Often patient complain of a definite upper level/ border below which sensations
are impaired. This upper border varies according to the level of compression[
 Root pain (Radiculopathic pain):due to irritation/ compression of nerve root
 Site: In the dermatome of the compressed root
 Character: Often severe, deep seated pain, may be aggravated with movements, coughing, sneezing.
Sphincteric disturbances: 1. Bowel dysfunction: Incontinence 2. Bladder dysfunction: Retention/ incontinence.
Signs: are present BILATERALLY often they are bilaterally asymmetrical
Complete cord compression/ transection
At the level of compression:

 Weakness with Bilateral LMN pattern of signs: Bilaterally (due to damage to AHC)
 Impairment of all sensations due to compression of dorsal root/ sensory fibres entering through it.
Below the level of compression:
 Weakness with UMN pattern of signs: Bilaterally I
 Impairment of all sensory modalities (superficial and deep) bilaterally.
Therefore upper level of sensory impairment corresponds to the dermatome of compressed segment.
Partial/ incomplete cord compression/ hemisection of spinal cord
At the level of compression:

 Ipsilateral LMN sign (due to damage to AHC)
 Impairment of all sensations in the dermatome of compressed segment: Ipsilateral (damage to dorsal root).
Below the level of compression:
 Ipsilateral UMN signs (due to damage to ipsilateral CST)
 Ipsilateral side: Impairment of deep sensation
 Contralateral side: Impaired pain and temperature sensation (due to damage of LSTT)
Motor manifestations Sensory manifestations Cord segment compressed
Upper limb: Weakness with Upper border/level of sensory loss Cervical cord
combined UMN and LMN signs somewhere in the upper limb As the level of compression goes down in
++ Cervical cord more and more part of Upper
Lower limb: Weakness with limb remains Neurologically intact
combined UMN and LMN signs
Thoracic cord
As the level of compression goes down in
Upper limb: No Weakness Thoracic cord the upper border of sensory
++ Upper border/level of sensory loss shifts towards the ABDOMEN
Lower limb: Weakness with loss somewhere in the trunk So,
UMN signs Upper thoracic compression: upper border
of sensory loss towards CHEST
Lower thoracic compression: upper border
of sensory loss towards ABDOMEN
Upper limb: No Weakness Upper border/level of sensory loss Lumbo sacral cord
++ somewhere in the Lower limb As the level of compression goes down in
Lower limb: Weakness with L-S cord more and more part of lower limb
combined UMN and LMN signs remains Neurologically intact
A probable localization of the level of spinal cord lesion can be assessed by noting some of the following features:
1. Distribution of weakness:
 High cervical lesion (C1-C5): Quadriparesis
 Low cervical lesion (C6-C8): Quadriparesis with proximal part of the upper limb spared
 Thoracic/ lumber lesion: Paraplegia.
2. Distribution of LMN signs: Seen in the same segment.
3. Upper level of sensory loss
4. Vertebral tenderness/ deformity:
Difference between extramedullary & intramedullary lesions of spinal cord
Features Extramedullary lesion Intramedullary lesion
Root pain Prominent an early Often not prominent/ late manifestation
(Dorsal root compression) manifestation
Pyramidal/ UMN sign Early manifestation Late manifestation, often spared
(CST damage)
Sacral sensory loss Early manifestation Late manifestation
Progression of symptoms Often rapid Often slow
Difference between ‘paraplegia in extension’ & ‘paraplegia in flexion’ (for Final MBs”)
Features Paraplegia in extension Paraplegia in flexion
Attitude of lower limb Extended Flexed
Plantar Extensor Extensor but may be accompanied by withdrawal
response
Pathophysiology Lesion of pyramidal tract Lesion of pyramidal tract as well as extrapyramidal
fibres
Some important etiology of chronic cord compression
1. Vertebral metastasis:
Common primary cancers: Breast Bronchogenic Prostate
Myeloma
Common site of metastasis: Thoraco-lumber vertebrae.
Symptoms:
 Low back pain is a prominent symptom
 Symptoms of primary malignancy may be present
2. Caries spine/ TB spine/ vertebral TB:
 It is due to hematogenous spread of bacilli
 Symptoms of PULMONARY TB may/ may not be present
 Causes of cord compression:
 Collapse of the vertebra
 Compression by paravertebral abscess
 Tubercular myelitis
 Vertebral tenderness may be present
 Local deformity may be present:
 Knuckle: prominence of 1 spinous process
 Gibbus: prominence of >1 spinous processes.
Investigation of compressive myelopathy

1. Imaging:
a. X Ray spine (to detect vertebral pathology, DOES NOT show the cord!!)
b. MRI Spine: THE MOST IMPORTANT Depending on the NATURE OF THE CAUSE….MRI is often the “last
 confirms cord compression & level investigation”…however further investigations may be required for
 Often “shows”the underlying cause confirmation, IF MRI is “suggestive but not confirmatory”
2. Further investigations to assess the underlying cause: IF/WHEN MRI is “suggestive but not confirmatory”
a. ”Local material”: may be required
 Biopsy/FNAC: if imaging suggests malignancy
 Abscess: Aspiration of pus: microbiological tests
b. PET CT or CT Chest + abdomen: To find out any suspected primary focus of malignancy
c. Biopsy/FNAC: if imaging suggests malignancy: any suspected primary focus
3. Blood:To assess the “effects” of the underlying disease

● Hb, TC, DC, ESR (↑ in infection) ● Liver function tests (Alkaline phosphatase level↑ in metastasis- Bone/Liver)
● Na+ K+ Urea creatinine ● Serum calcium (↑ in bone metastasis/ also in Myeloma)
● Special blood test: Serum Protein Immunoelectrophoreis ( To confirm Multiple Myeloma)
Treatment
Supportive
1. Immobilization of the spine (particularly in case of VERTEBRAL fracture/collapse)
 Devices: Collar/Brace
2. Absolute bed rest
3. Bed sore prevention (if applicable)
4. Catheterization (if required)
5. Drugs:
●Anti-edema: Corticosteroid- Dexamethasone: in case of Malignant compression (to reduce spinal cord edema)
● Analgesic
6. DVT prophylaxis
7. Exercise: Physiotherapy (when safe to start)
Definitive: depending on the CAUSE: 1. Pharmacological 2. Surgical 3. Radiotherapy
1. Pharmacological:
a. TB: Anti-tubercular drug
b. Spinal abscess: IV antibiotic
2. Surgical: Neurosurgical/ Orthopedic surgery
Details of Neuro/Orthopedic surgery..
 In following CAUSES: Fracture/Prolapsed Disc/Spinal cord tumor Just another few years…wait till you
3. Radiotherapy: In case of metastasis become MS/MCh!!
DD of cord compression
1. Acute cord compression (spasticity yet to develop)- Shock STAGE: Other causes of “Acute flaccid paralysis”
 Acute Transverse Myelitis in shock stage
 Acute Inflammatory Demyelinating Polyradiculoneuropathy( GB syndrome): No H/O sensory loss/ bowel-bladder
disturbance
 Acute lesion in spinal cord (non-compressive): Ant. Spinal artery occlusion/ thrombosis.
2. Acute cord compression (spasticity has developed):
Acute transverse myelitis
3. Chronic cord compression: Other diseases causing paraparesis/ quadriparesis with spasticity may mimic chronic
cord compression. These include non-compressive myelopathies:
a. Motor neurone disease
All these diseases will have NO upper border of sensory
b. Multiple sclerosis
loss and bowel-bladder disturbance is NOT prominent
c. Subacute combined degeneration of spinal cord
Non-compressive myelopathy
Many diseases…each “damages” the cord by it’s “OWN UNIQUE” way… These diseases have structure predilection
OR “Structure selection bias”….so UNLIKE compressive myelopathy there is no “FAMILY” manifestations….
So, EACH DISEASE BEHAVE IN AN INDEPENDENT WAY
Diseases:
Rapid/Acutely developing diseases Slowly developing diseases
Acute transverse myelitis** Motor neuron disease (MND) **
Spinal artery Thrombosis Tabes Dorsalis
Multiple Sclerosis Friedrich’s Ataxia
Subacute Combined Degeneration of the cord**
**Enough for an Undergraduate!!
Acute transverse myelitis( ATM)

Rapidly progressive inflammation of the spinal cord, where the inflammatory process often extends transversely as
well as longitudinally for 1-2 segments.
Etiology
1. Most likely, the inflammation is an autoimmune response likely to be triggered off by different viruses
2. Autoimmune disease can cause ATM
3. Complication of an old (& obsolete!) generation rabies vaccine (that’s why still asked in “Final MB”by some….!!)
Pathophysiology
Rapid accumulation of As the inflammation

Inflammation of cord "Strangulation" of the cord subsides, usually there is
inflammatory exudate
complete recovery
Very interesting & important!!!...inflammatory process is NOT a “compressive” one…BUT “strangulating”
effect will affect ALL the structures within the cord WITHOUT any “selection bias”!!!
Symptoms
1. Prodromal symptoms May precede the paralysis: fever, malaise, bodyache
2. Rapidly progressive weakness:
a. Usually starts with both lower limbs
b. Upper limbs are often spared as the inflammation commonly occurs in the thoracic segment
c. Rapidly progressive sensory impairment with a definite upper level above which sensations are normal.
3. Prominent sphincteric disturbance:
a. Acute retention of urine/ urinary incontinence
b. Fecal incontinence
Often symptoms/signs start to improve after few days, leading to complete recovery, in some patients, a degree of
residual weakness may persist for long term.
Sign
Spinal shock stage: days to weeks Stage of paralysis: days to weeks Stage of recovery:
Power: ↓ Power: ↓ Power and sensation gradually

Tone: ↓ (Flaccid) Tone: ↑ (Spastic) start to return
Deep tendon reflex (DTR): ↓/- DTR: ↑↑ (clonus may be present) UMN signs and sensory signs
Plantar: Bilateral extensor (Upgoing) Plantar: ↑ gradually disappear
Wasting/ fasciculation: Absent Sensory: Impairment/ loss of all
Sensory: Impairment/ loss of all sensation sensation with a definite upper level
with a definite upper level
ATM behaves EXACTLY like “Cord compression”….still it’s “Non compressive” as pathology is “INFLAMMATION”
ATM therefore can be described as…” A non compressive lesion behaving EXACTLY like Cord compression”
Investigations
1. MRI of spinal cord: Confirmatory
2. Lumber puncture:
a. WBC count (slightly ↑)
b. CSF protein (Normal/ slightly ↑) NO albumin-cytological dissociation.
3. Routine investigations: Hb, TC, DC, CRP, Na+, K+, Urea, Creatinine
Treatment
Supportive:
A. Absolute bed rest
B. Bed sore prevention
C. Catheterization
D. DVT prophylaxis
E. Exercise, physiotherapy and walking aids.
Definitive: Systemic corticosteroid
DD of ATM
Shock STAGE: Other causes of “Acute flaccid paralysis”
 Acute compressive myelopathy in shock stage
 Acute Inflammatory Demyelinating Polyradiculoneuropathy( GB syndrome): No H/O sensory loss/ bowel-bladder
disturbance
 Acute lesion in spinal cord (non-compressive): Ant. Spinal artery occlusion/ thrombosis.
Spastic stage: Acute compressive myelopathy post shock stage
Motor neuron disease (MND)
It is a chronic degenerative disease affecting motor neurons.
Affected motor neurons: BILATERAL INVOLVEMENT
UMN
Corticobulbar fibres Predominantly Corticonuclear fibres to bulbar cranial
Motor nerve nuclei are affected
Neuron
Anterior horn cell
LMN Predominantly bulbar cranial nerve nuclei are affected
Cranial nerve nuclei*
Types of motor neuron diseases:
Motor neuron disease
Pure UMN Type Pure LMN type Combined/Mixed (UMN + LMN) type
Spinal disease Spinal disease
(affecting CSF) (affecting AHC)
Bulbar disease
Bulbar disease
(affecting BCNN)
(affecting CBF) CSF: Corticospinal fibres
CBF: Corticobulbar fibres
AHC: Anterior horn cell
Spinobulbar BCNN: Bulbar cranial nerve nuclei
Spinobulbar
Amyotrophic lateral sclerosis (ALS)

It is the commonest variety of motor neuron disease characterized by combined (UMN + LMN) degeneration.
Symptoms
1. Bulbar:
 Dysphagia
 Dysarthria
 Dysphonia
 Nasal intonation of voice
 Nasal regurgitation of food
 Recurrent episodes of chocking/ aspiration leading to aspiration pneumonia.
2. Spine:
 Slowly progressive para/quadri-paresis
 Wasting: Particularly of small muscles of hand, often very prominent
 No sensory disturbances
 No sphincteric disturbances.
Signs
Bulbar involvement:
Tongue:
 Wasting and fasciculation: May be present
 Pharyngeal reflex: Lost
 Gag reflex: May/ may not be brisk
Patient may be emotionally labile, leading to unprovoked spells of laughing/ crying (due to pseudobulbar palsy).
Spinal involvement:
Upper limb: Combined (UMN + LMN) signs
 Power: ↓
 Tone: Spastic (due to UMN type of damage), but some muscles may be flaccid (due to LMN type of damage)
 Wasting: Some muscles may be wasted
 Fasciculation: May/ may not be present
 Reflexes: Some are Brisk but some atr absent in varying combinations.
Lower limb:
 Usually spastic weakness (due to predominance of UMN signs)
 Jerk: Brisk
 Wasting and fasciculation: Absent
 Plantar: Bilateral extensor
 As the disease progresses, lower limb will also show superadded LMN signs.
Functions which will remain unaffected in ALS:
1. Higher function
2. Function of extraocular muscles
3. Sensory function
4. Sphincteric function
Complications of ALS
1. Respiratory paralysis, leading to type respiratory failure
2. Recurrent episodes of chocking/ aspiration, leading to recurrent episodes of aspiration pneumonia.
Investigations
1. Nerve conduction velocity (NCV)/ Electromyography (EMG)
2. MRI spine: To rule out any structural compression of spinal cord.
Treatment
Supportive
B. Bed sore prevention Breathing: Long term ventilatory support.
C. Catheterization (if required)
D. Diet:: Maintenance of nutrition may be difficult due to swallowing difficulty, often patient requires feeding
jejunostomy or PEG (Percutaneous endoscopic gastrostomy) tube.
E. Exercise and physiotherapy
Definitive: Riluzole
D/D of ALS
Patient with quadriparesis: Cervical compressive myelopathy:Here (sensory + sphincteric) disturbances are present
Patient with wasting of small muscles of hand:
1. Lower cord compression (C7-C8)
2. Plexopathy
3. Peripheral neuropathy
4. Pancoast’s tumor (C8-T1 compression).
Conus medullaris and Cauda equina lesions ( NOT a “must know topic”)
Points Conus medullaris lesion Cauda equina lesion
Definition Conus medullaris is the terminal Cauda equina is the lower spinal nerves containing
tapering end of spinal cord lower lumber, sacral and coccygeal nerves: all of
containing lower sacral and which descend towards their exit through
single coccygeal segment. intervertebral foramina.
Graphical representation
Clinical features
Lower limb weakness Absent Present, usually variable and asymmetrical
Lower limb jerk Normal Asymmetrical hypo-reflexia/ a-reflexia
Sensory loss From perianal and perineal Asymmetrical sensory loss in both lower limbs
region
(Saddle back anesthesia)
Sphincteric disturbance Very prominent Not common
Etiology Lumbosacral vertebral diseases
Surgery Often considered Not commonly considered
Investigation MRI spine
Neuropathies
Depending on the CAUSE/ DISEASE affecting the peripheral nerves Neuropathy can be(from the point of view of)
Mode of onset and progression: Acute (& rapidly progressing) OR Gradual (& slowly progressing)
Number(s) of Nerve affected: Mononeuropathy OR Polyneuropathy
Type(s) of Nerve fibre affected: Predominantly Motor OR Predominantly Sensory OR Predominantly Autonomic
(Rarely “Mixed”- combination of above
Guillain-Barré Syndrome (GB syndrome)/ Acute inflammatory demyelinating polyneuropathy (AIDP)
It is a disease characterized by rapidly progressing inflammatory demyelination of multiple, predominantly motor
peripheral nerves (nerve roots may also be damaged).
Etiopathogenesis: Most likely inflammatory reaction is triggered off by a recent infection: URTI/ GI infection.
Clinical features: Preceding history of an URTI (fever, sore throat, cough) or GI infection (diarrhea, abdominal pain
etc.) MAY be present.
Symptoms:
1. Rapidly progressive weakness: Usually starts with lower limb, then ascends
2. To start with proximal weakness is more than distal weakness in distal, but eventually whole limb gets affected
3. Sensory symptoms: NO sensory loss (Rarely complains of a deep seated pain in the limbs due to root involvement)
4. Respiratory distress and drowsiness due to Respiratory muscle paralysis
(type 2 respiratory failure: hypoxemia with hypercapnia).
5. Sphincteric disturbance is very rare
Signs:
Motor: (Neuropathy= LMN lesion)
1. Paraparesis/ Quadriparesis
 Initially proximal weakness> distal weakness
 Symmetrical weakness usually present
2. Tone: Flaccid Nerves are part of LMN, So affected parts show
3. Deep tendon reflexes/ Jerk: absent/ diminished LMN pattern of signs
4. Plantar: Lost/ unresponsive/ flexion (But never extensor)
5. Wasting and fasciculation is absent in most of the cases due to rapidity of the progression of disease
Sensory: No objective sensory signs

Cranial nerves: Bilateral 7th cranial nerve LMN type of palsy may be present
Paralysis of respiratory muscles:
1. Respiratory distress
2. Tachypnea
3. Low Oxygen saturation
4. Low GCS: Due to drowsiness resulting from retention of CO2
Investigation
1. NCV: Confirms the diagnosis. In NCV, two types of lesion are seen:
a. Demyelinating type
b. Axonal damage type (bad recovery).
2. CSF/ Lumber puncture:
a. Protein: Markedly increased This is called ‘albumino-cytological dissociation’
b. WBC: Normal
3. Bedside spirometry: FVC↓
Treatment
1. Supportive treatment: 2. Definitive treatment: 2 options
● Bed rest ● IV injection of IgG for 5 days
● Bed sore prevention ● Plasmapheresis
● Breathing support: Ventilation for/when Respiratory paralysis
● Catheterization
● DVT prophylaxis
● Exercise: Physiotherapy
Differential diagnoses: Other causes of “Acute flaccid paralysis”
1. Shock stage of acute transverse myelitis
2. Shock stage of acute compressive myelopathy & although it’s a disease of the “PAST”….still Polio
Miller Fisher Syndrome It is an atypical variant of GB
Clinical features: All clinical features + ophthalmoplegia + ataxia
Investigation:
1. NCV
2. LP
3. Presence of Anti Gq1b antibody
Treatment: As in GB syndrome.
Polio
It is a disease characterized by rapid degeneration of anterior horn cell (AHC).
Causative agent: Poliovirus type 1, 2, 3.

Clinical features
There are 4 types of outcome in a polio patient:
a. Asymptomatic
b. Abortive
c. Non-paralytic polio (neck stiffness + meningeal signs)
d. Paralytic polio.
Course of paralytic polio (in comparison to GB)
1. Prodromal illness:
 Fever
 Malaise
 Neck pain
 Neck stiffness
 Constipation. Asymptomatic latent period: Absent in polio
2. Weakness: GB vs Polio…”for Final MB”!!
 Rapidly progressive Para/quadri-paresis
 Proximal weakness is more prominent throughout the course of illness
 Bilaterally asymmetrical involvement
 Tone of affected limb: ↓ GB
 Reflex: ↓/-  Both proximal & distal weakness
 Bilaterally symmetrical involvement
 Plantar: Unresponsive/ flexor
 Fasciculation: Usually absent
 Fasciculation: Usually present
 Wasting: Not Prominent
 Wasting: Prominent
 Recovery: often good (with treatment)
 Recovery: Very poor
 Signs of LMN type bulbar palsy
 Autonomic dysfunction: May occur
 Respiratory paralysis with failure: May occur
 (Sensory + Sphincteric) disturbance: Absent
Investigation: Detection of virus in stool sample
Treatment
 Established case: Supportive
 Primary prevention: Vaccination
Peripheral neuropathy
Causes
A  Alcoholic neuropathy
B  B Vitamin B deficiency: B6, B12 (B6 deficiency is commonly seen in INH therapy.
C  CIDP (Chronic inflammatory demyelinating polyneuropathy)
 Chronic renal failure
 Carcinomatous neuropathy (Paraneoplastic syndrome)
 Connective tissue disease (vasculitis)
D  Diabetes
 Drug induced: Causes: Alternative way!
 Amiodarone 1. Diabetic neuropathy
 Anticancer drugs 2. Non diabetic causes
 Anti-retroviral drugs
E  Endocrinopathy (Hypothyroidism)
 Exogenous toxins: Lead/ Arsenic toxicity
F Familial: Hereditary sensory motor neuropathy/ Charcot Merry Tooth disease
G  GB [also called Acute inflammatory demyelinating polyneuropathy (AIDP)]
H  HIV
 Hansen’s disease (Leprosy)
Clinical features
1. Due to the underlying disease
2. Due to neuropathy itself: DEPENDING ON the underlying cause/disease
Mode of onset and progression of manifestations: Acute (& rapidly progressing) OR Gradual (& slowly progressing)
Manifestations present in the distribution of : Single OR Mutiple nerves (Mononeuropathy OR Polyneuropathy)
Pattern/ type of manifestations: Predominantly Motor OR Predominantly Sensory OR Predominantly Autonomic
Motor: at the level of the lesion= along/in the area served by the affected Nerve(s)= Myotomal distribution
Weakness:
 Uni/bi-lateral
 Asymmetrical
 Patchy in distribution: Involving only that part of the limb which is innervated by the affected nerve
 Often starts with distal weakness
 LMN signs present in the affected part of the limbs:
● Flaccidity ● Reflex: ↓/-
● Wasting: Present ● Fasciculation: Absent
● Plantar: Never extensor (Unresponsive/ flexor)
Sensory: at the level of the lesion= along/in the area served by the affected Nerve(s)= Dermatomal distribution
 Sensory impairment:
 Paresthesia: Tingling/ pins and needle sensation
 In some cases (eg. diabetes): severe burning pain
 Unilateral/ bilateral (asymmetrical)
 Sensory loss:
 Patchy in distribution: From the dermatome of the affected nerve
 Distal part of limb is affected first (Glove and stocking distribution).
 Neuropathic ulcer: Often present.
Autonomic:
 Gastro-intestinal: Constipation due to hypomotility
 Genito-urinary: Sphincteric disturbance/ Impotence
 Postural hypotension
Investigations
1. To Confirm neuropathy NCV
2. Diagnosis of underlying disease
 Hb, TC, DC, ESR/CRP
 Urea creatinine
 FBG, PPBG
 Serum B12
 Serum TSH
 Vasculitic Autoantibodies
Management
1. Treatment of underlying cause/ disease
2. Supportive treatment for neuropathy
 Motor dysfunction: ● Physiotherapy ● Mobility aid ● Protective splints
 Sensory dysfunction: ● Foot/ limb care ● Prevent/ urgently treat any infection ● Avoid trauma
 Drugs for neuropathic pain: ● Amitryptiline ● Gabapentin ● Pregabalin
 Autonomic neuropathy:Symptomatic treatment
Myasthenia Gravis
Autoimmune disease characterized by fatiguable weakness and is usually due to autoantibody against post-synaptic
acetylcholine receptor.
Clinical association: Thymoma (most commonly)
Pathophysiology
1. There is auto-antibody mediated blocking of Ach receptor in the post-synaptic membrane resulting in too few
functional Ach receptor.
2. Simultaneously, there is exaggeration of physiological rundown of Ach in the pre-synaptic membrane.
Both of these are responsible for impaired N-M transmission which gets further compromised on repeated contraction
of muscle leading to fatigable weakness.
Clinical features
The type of weakness is fatiguable; so signs and symptoms become more prominent as the muscle continues to work
continuously.
1. Ocular muscle weakness:
a. Drooping
b. Extra-ocular muscle fatigue: Diplopia
c. Extra-ocular muscle weakness: External ophthalmoplegia (distribution of weakness does not follow any
specific cranial nerve pattern)
d. Ptosis: Usually fatigable
e. No pupillary abnormality.
2. Facial weakness
3. Weakness of bulbar muscles
4. Limb weakness:
a. Fatiguable weakness
b. Tone, reflex, jerk, plantar: Usually normal
c. Wasting, fasciculation: Absent.
5. Respiratory muscle weakness/ paralysis
a. Respiratory distress
b. Tachypnea
c. Low Oxygen saturation
d. Low GCS: Due to drowsiness resulting from retention of CO2
Investigation
1. Edrophonium challenge test/ Tensilon test: Dramatic improvement of weakness
2. NCV (tests the nerve)/EMG (tests the muscle): Detrimental response on repetitive stimulation of muscle
3. Ach-R antibody
4. Antibody against Muscle Specific Kinase (Anti MuSK):
 Present in many patients who are Ach-R antibody negative
 Predictor of respiratory paralysis
5. CT chest: To look for thymoma.
Treatment
1. Stable stage:
a. Neostigmine/ Pyridostigmine (anti-cholinesterase)
b. Corticosteroid
c. Immunomodulators (Micophenolate mofetil)
2. Myasthenia crisis (acute respiratory failure/ acute limb weakness):
a. IV IgG/ Plasmapheresis
b. Ventilatory support
c. Thymectomy
SN: Lambert Eaten Myasthenia Syndrome
Paraneoplastic syndrome associated small cell lung carcinoma. It is due to anti Ca++ channel antibodies in pre-
synaptic membranes.
Clinical features:
Same as myasthenia gravis except:
1. Weakness improves with repeated muscle contraction
2. Areflexia occurs
3. Autonomic disturbances occur.
Diagnosis: EMG: Incremental response on repeated stimulation
Treatment: Di-amino-pyridine
It may manifest even before lung Ca appears radiologically. So a patient with LEMS must be periodically screened by
X-Ray to detect any obvious mass on the earliest opportunity.
Cerebrovascular Accident/Stroke
Abrupt onset focal neurodeficit lasting for >24 hours due to a vascular event.
Type
1. Ischemic stroke: Occlusion of a cerebral vessel 2. Hemorrhagic stroke: Bleeding into brain
a. Thrombotic stroke: Thrombus in situ OR Artery to artery embolism of the thrombus
b. Embolic stroke: Cardio embolism
Risk factor/etiology
Ischaemic stroke: result from events that limits or stop blood flow: EITHER due to extracranial or intracranial
thrombotic embolism OR thrombosis in situ
A: Atherosclerotic Cerebrovascular disease:
a) Arterial hypertension
b) BMI
c) Cigarette
d) DM A+ B= thrombus in situ + artery to artery embolism
e) Exercise lack
B: Non atherosclerotic CV disease: atypical causes of ischaemic stroke, but common causes in young patients
 Arterial dissection
 Abuse of: Cocaine, Amphetamines
 ↑↑Blood coagulation (Hypercoagulable) state: APLA syndrome, Protein C deficiency, Protein S deficiency
 Sickle Cell disease
 Fibromuscular Dysplasia
C. Cardioembolism: Risk factors/ causes are:

A. Atrial fibrillation: MOST IMPORTANT
 Valvular AF: AF associated with Mitral stenosis
 Non-Valvular AF
B. Infective endocarditis
C. Intracardiac aneurysm: Mural thrombus: Post MI patients
D. Paradoxical embolism: Rt sided thrombus to left Heart through an Intracardiac defect: Patent Foramen Ovale
Hemorrhagic stroke:
A:
 Arterial hypertension
 Aneurysm rupture
 AV malformation rupture
 Anticoagulant/ antiplatelet therapy
 Accident: Head injury
B: Bleeding disorder

1. Due to damage to corticospinal and corticonuclear fibres innervating lower ½ of 7th cranial nerve nucleus
2. Damage to other structures: depending upon the site of lesion: These help us to localize the site of lesion
3. Due to underlying etiology/ risk factors
4. Due to raised ICT (resulting from compressive effect of blood and/or intracerebral edema)
Symptoms: Following in varying combination
1. Damage of corticospinal and corticonuclear fibres innervating lower ½ of 7th cranial nerve nucleus:
● Contralateral Weakness: Upper limb &/or Lower limb &/or Lower part of the face (Deviation+ Dysarthria)
And/or
2. Damage of Cranial Nerve nucleus/fibres in the brainstem:
 Diplopia An Alternative way to remember!!
 Deviation of face Altered sensorium
 Dysarthria Body part weakness:
 Dysphagia Upper limb
 Dysphonia and/or
And/or Lower Limb
3. Damage to Higher cortical centres: Dysphasia and/or
And/or Lower part of face
4. Rising ICT : Falling Consciousness level/Loss of consciousness Consciousness loss
D: Diplopia
5. Due to underlying risk factors: following risk factors Dysarthria
a. Obesity Dysphagia
b. High BP Dysphonia
c. Cigarette smoking Dysphagia
d. Dyslipidemia Etiology: features due to underlying risk factors
e. Lifestyle (Exercise lack)
f. h/o Arrhythmia: Palpitation/syncope
g. H/o Valvular Heart disease
Signs:
1. Those due to underlying risk factors: These if present helps to predict the cause and type of stroke:
a. BP: Hypertension
b. Pulse:
 Irregular- AF
 Poor distal pulses: Atherosclerotic disease
 Carotid Bruit: Atherosclerosis
c. Murmur of MV disease
2. Neurological signs: Helps to suspect stroke and localization of site of lesion

Site of Clinical features
lesion
Cortex 1. Contralateral hemiparesis with UMN signs (CST damage)
2. Contralateral lower facial weakness (UMN type CN7 palsy):
Asymmetrical weakness/ monoparesis/ facial weakness only
3. Contralateral homonymous hemianopia (Optic radiation/tract damage)
4. Aphasia: usually seen in left sided lesion (as speech area is usually right sided)
a. Fluent aphasia(Wernicke’s): comprehension defect
b. Non-fluent aphasia(Broca’s): expressive defect
Internal 1. Contralateral UL & /or LL &/or Lower part of the face weakness with UMN signs
capsule 2. Contralateral lower facial weakness: UMN type CN7 palsy
Midbrain 1. Contralateral UL & /or LL&/or Lower part of the face weakness with UMN signs
2. Contralateral lower facial weakness- UMN type CN7 palsy
3. Ipsilateral 3rd CN palsy
4. Ipsilateral 4th CN palsy (1+3= Weber’s syndrome)
Pons 1. Contralateral Upper limb & /or Lower limb with UMN signs
2. Ipsilateral LMN type of 7th CNpalsy
3. Ipsilateral 6th CN palsy
4. Loss of touch sensation from ipsilateral ½ of face (Principal sensory nucleus of CN5
5. Ipsilateral Horner’s syndrome (Descending Sympathetic trunk damage)
6. Loss of pain and temperature sensation from contralateral ½ of body (LSTT damage)
Medulla 1. Contralateral Upper limb & /or Lower limb

2. Ipsilateral LMN type of CN 12 palsy
3. Ipsilateral LMN type of CN 9, 10, 11 palsy
4. Loss of pain and temperature sensation from ipsilateral ½ of face(spinal nucleus of 5th cn)
5. Ipsilateral Horner’s syndrome (Descending Sympathetic trunk damage)
6. Loss of pain and temperature sensation from contralateral ½ of body (LSTT damage)
7. Loss of deep sensation from Ipsilateral half of the body ( Dorsal column pathway)
8. Vertigo, vomiting, nystagmus (vestibular nucleus damage)
Cerebellum A: Ataxia:gross incoordination of muscle movements. May be very unsteady on their feet & SWAYS
towards the side of the lesion
B: Broad, coarse tremor that typically worsens as an extremity approaches the endpoint of deliberate
and visually guided movement (hence the name intention tremor)
C: Co-ordination lack
D:
Dysdiadokinesia:inability to perform a series of rapidly alternating muscle movements (typically
flipping one hand rapidly on the palm of the other)
Dysmetria: lack of coordination of movement typified by the undershoot or overshoot of intended
position with the hand
E: Eye: Nystagmus
F: Floppy (Hypotonic) Muscles
Clinical features which may help us to get an idea about the underlying type of stroke are as follows:
Patients with intracerebral bleeds are more likely than those with ischemic stroke to have headache, altered mental
status, seizures, nausea and vomiting, and/or marked hypertension. Even so, none of these findings reliably
distinguishes between hemorrhagic and ischemic stroke.
Ischemic Hemorrhagic
Features Thrombotic stroke Embolic stroke Hemorrhagic stroke
Onset and evaluation Sudden. At times, it progresses Sudden in onset Sudden in onset
over few hours affecting one part Simultaneously affects all Simultaneously affects all the
after another(stuttering onset) the parts parts
Preceding symptoms H/O a preceding TIA may be present ××-

Associated symptoms Rare Rare May be present
1. Unconsciousness (due to sudden rise of ICT)
2. Hedache This is an useless (so “Final MB” type) table…often
3. Vomiting asked by some…“….” in Long case!!
4. Convulsion
History H/O angina/ claudication may be H/O palpitation/ H/O hypertension may be +
+ present syncope may be +
Pulse - Irregular pulse (if AF) -
Murmur - Murmur of MS may be + -
Risk factor Atherosclerotic risk factors AF Risk factors of hemorrhage
A doctor clinically (try to) diagnoses 1. Stroke 2. Underlying Risk factors………Investigations diagnoses the
type- Ischemic OR Hemorrhagic!!!!
Investigation of stroke
1. Imaging: to confirm the diagnosis
Imaging tells us the type
1. CT head
Ischemic stroke: Shows the INFARCT
2. MRI (in selected cases)
Hgic. stroke: Shows the BLEED
2. Risk factor stratification
1. Blood sugar (Fasting + Post-prandial)
2. Fasting lipid profile
3. ECG
4. Echocardiogram
5. 24 hour ECG monitoring (in selected cases: suspected paroxysmal arrhythmia)
3. Routine investigation
1. Blood: Hb, TC, DC, ESR
2. Renal function: Na, K, Urea, Creatinine
3. Coagulation profile: BT, CT, PT, aPTT
4. Special investigation: these are the investigations which are done IF an atypical/rare cause of stroke is suspected
from clinical background of patient
1. If vasculitis is suspected: a. detection of autoantibodies b. Cerebral Angiography( CT angio/ MR angio)
2. If aneurysm/AV Malformation is suspected: Cerebral Angiography( CT angio/ MR angio)
3. If hypercoagulable disorder is suspected: Tests to rule out hypercoagulable disorders
4. If cerebral venous thrombosis is suspected: MR venogram
Treatment: ● Urgent/Immediate treatment ● Risk factor modification ● Supportive treatment
1. Immediate treatment: Specific treatment: Depends on the TYPE of Stroke

a. Ischaemic stroke: IF the patient fulfills the criteria of thrombolysis: THROMBOLYSE with r-TPA- Alteplase
b. Hemorrhagic stroke: Urgent Neurosurgical intervention: Evacuation of Hematoma (in selected cases)
You may have a dream to become a Stroke
2. Risk factor modification: Prevention of future stroke/risk reduction
specialist or Neurosugeon….one day you
a. Lifestyle modification: for underlying risk factors definitely will be one…BUT don’t be a
b. Pharmacotherapy: “day dreamer” & start considering
Antiplatelet(prevents thrombus formation): in “Nonembolic ischaemic”stroke yourself one from now!!!....
 Aspirin OR Clopidogrel for rest of the life “….fulfills the criteria”& Neurosurgical
intervention is ENOUGH!!
Anticoagulant: in case of cardio-embolism:
 Warfarin/NOAC Antiplatelet vs Anticoagulant decision making
Antihypertensive agents CT/MRI showing ischemic stroke…..
Antidiabetic drugs AF present (ECG or Holter)….presumed Cardioembolic stroke
Antilipidemic drugs: Atorvastatin No AF….“Nonembolic ischaemic”stroke
3.Supportive treatment: Prevention/ treatment of complications: therefore depends on the clinical scenario
A. Airway protection (± oropharyngeal suction ± intubation, if required)
Absolute bed rest Oral anticoagulant
B. Breathing support (oxygen ± invasive ventilation) Warfarin (Vit K antagonist)
Bed sore prevention (change of posture/air or water mattress) Non-Vitamin K Antagonist Oral AntiCoagulant
 Dabigatran (NOAC)
C. ● Circulatory support (IV fluid, if required)● Catheterization  Apixaban
D. Diet:  Rivaroxaban
● Oral feeding (if swallowing intact)
● Tube feeding (if swallowing impaired)
● Short term: Ryle’s tube feeding ● Long term: Feeding jejunostomy/Percutaneous endoscopic gastrostomy tube
Drugs:
 Anti-edema measures: IV mannitol
 Anticonvulsant: if there is post stroke seizure
 Antibiotic: if any focal infection is suspected
 Cerebro-active/protective agents: Piracetam/ Citicoline/Cerebrolysin: EXTREMELY doubtful role
E. Exercise (Physiotherapy) (Calcuttan drugs!!)
Transient ischemic attack (TIA)

Focal ischaemia of brain leading to reversible focal neurodeficit lasting usually <24 hours
Risk factors
1. Non embolic TIA: Thrombosis (Thrombus in situ/artery to artery embolism of a thrombus):
The main cause is ATHEROSCLEROTIC cerebrovascular disease: Risk factors are
Abdominal obesity
BP↑
Cigarette smoking
Diabetes/ Dyslipidemia
Exercise↓
2. Cardio-embolism: Risk factors/ causes are:
 Atrial fibrillation: Valvular AF/Non- Valvular AF (MOST IMPORTANT)
 Infective endocarditis
 Intracardiac aneurysm: (Mural thrombus)
 Paradoxical embolism: Rt sided thrombus to left Heart through an Intracardiac defect: Patent Foramen Ovale
Clinical features of TIA: Clinically, TIA may be classified into 2 groups, each of which has some distinct clinical
features, which may appear in varying combinations involving the particular areas affected:
Carotid TIA Vertebro-basilar TIA
Contralateral Hemiplegia (Corticospinal fibres) Diplopia (CN 3,4,6)
and /or
Contralateral Hemifacial weakness (CN fibres)
Contralateral Hemisensory loss (Sensory fibres or Sensory area)) Dysarthria/ Dysphagia (Bulbar nuclei)
Contralateral Homonymous hemianopia (Optic radiation) Dys-equilibrium (Cerebellum)
Aphasia (Speech area) Vertigo and vomiting
Amaurosis fugax (Transient loss of vision whish Some patients Contralateral hemiparesis (CST fibres)
describe “as a gray or black shade coming down over their eye” Contralateral hemisensory loss (LST fibres)
or “a curtain is coming down in front of the eye”
cause: retinal artery occlusion
All the patients of TIA should be assessed for:
1. Atherosclerotic risk stratification 3. Cardiac murmur
2. Atrial fibrillation 4. Carotid bruit
Investigation
1. Brain imaging: CT head MRI brain
2. Risk stratification
 Fasting/ postprandial blood sugar
• Lipid profile
• ECG
• 24 hour ECG in selected cases
• Echocardiogram
3. Carotid Doppler USG: Look for for any atherosclerotic plaque/narrowing which has may influence treatment plan
Treatment
1. Non pharmacological mangement: Life style factor modification for risk factors, if any
2. Pharmacotherapy:
Prevention of future stroke:
 Non embolic TIA: Antiplatelet : Aspirin OR Clopidogrel
 Anticoagulant (Long term Warfarin/NOAC in case of cardiac embolism)
Risk factor modification:
 Antilipidemic drug
 Antihypertensive drug
 Antidiabetic drug
3. Surgical treatment: Carotid endarterectomy if >70% stenosis of internal carotid artery
ABCD2 scoring:
Scoring system which can reliably predict short and Long term risk of stroke in a patient of TIA and thus helps to
prognosticate TIA
A. Age> 60 years :1
B. SBP> 140 mm Hg and/or DBP> 90 mm Hg: 1
C. Clinical features: ● Only speech disturbance:1 ● Weakness WITH OR WITHOUT Speech disturbance: 2
D. Duration: ● >1 hour: 2 ● Less than 1 hour: 1
Scoring Implication
D. Diabetic: 1
0-2 Low risk (does not require hospitalization)
3-5 Moderate risk (Hospitalization may be considered)
6-7 High risk (Hospitalization recommended)
Subarachnoid hemorrhage (SAH)

Bleeding inside subarachnoid space
Etiology
A: ● Aneurysm rupture: Rupture of a saccular aneurysm (Berry aneurysm) ●AV malformation rupture
● Arterial hypertension ●Anticoagulant/ antiplatelet therapy
● Accident: Head injury
B: Bleeding disorder
Clinical features
1. Headache
o Onset: Sudden
o Site: Often occipital (due to vertebro-basillar artery aneurysm rupture)/ neck pain but may be generalized
o Nature: Usually severe, often described by the patient as “worst headache of my life”
2. Focal neurodeficit: Not very common, can occur under following 2 circumstances:
a. IF an aneurysm starts to compress surrounding structure
b. Due to intense cerebral vasospam (common after a SAH) which may lead to focal ischaemic injury
3. Meningeal signs: Usually develops 48 to 72 hours after SAH: Neck rigidity and/or Photophobia may be present
Investigation
Blood: ● Hb, TC, DC, CRP/ESR ● Renal function: Na+ K+ Urea creatinine ● Coagulation profile: PT, aPTT
Definitive:
1. CT Head (sensitive to detect hemorrhage): Confirms SAH BUT CT can be falsely negative
2. If CT is inconclusive: Lumbar puncture: CSF study
 Appearance: Blood tinged; RBC count: high
 Xanthochromia: Yellowish green discoloration of CSF due to presence of bilirubin/ other pigment. It usually
takes 12 hours to develop. Therefore, ideally LP should be performed atleast 12 hours after onset of symptoms.
3. Cerebral angiogram: CT Aangio/MR Angio/ DSA (Digital subtraction angiography).
Blood tinged CSF with High CSF RBC: may be due to 2 causes and can be differentiated by following:
o Continuous leak of blood stained CSF: Due to SAH
o Gradually the blood staining gets clear: Due to traumatic tap
CSF RBC count: In case of traumatic tap, there will be a significant drop in RBC count between sample 1 and sample 3
In case of SAH, there will be no such drop
Treatment: 1. supportive 2. Definitive (interventional)
A. Absolute bed rest for 48-72 hours (if patient prefers than in a dark room)
Analgesic
B. Bowel: Laxatives (to avoid any straining during defecation)
C. Circulatory support: IV fluid (to maintain adequate hydration)
D. Drugs: Nimodipine (to counteract cerebral vasospasm).
Interventional treatment: Neuroradiological intervention: Clipping/Coiling of the aneurysm

Complications 1. Obstructive hydrocephalus 2. Vasospasm 3. Rebleeding
SN: Saccular aneurysm/Berry aneurysm
Outpouching of an arterial wall of cerebral blood vessels usually due to congenital weakness of the wall.
Site: Can occur anywhere in the Circle of Willis but common sites are:
1. Distal of ICA
2. Bifurcation of MCA
3. Top of Basillar artery
Associations: ● Coarctation of aorta ● Polycystic kidney disease
Description: Aneurysm has two parts: a neck and an apex. Rupture usually occurs at the apex. Size of the aneurysm
correlates poorly with risk of rupture.
Clinical features:
• Before rupture: CN3 palsy/ Homonymous hemianopia: due to compressive effects
• After rupture: SAH: c/f of SAH
Investigations: SAH
Treatment: SAH
Parkinsonism
It is a disease of extrapyramidal tract characterized by imbalance between dopamine and acetylcholine leading to a
triad of Bradykinesia + Rigidity + Tremor.
Etiology:
1. Primary: Idiopathic (Parkinsons disease)
2. Secondary
Atherosclerotic (vascular parkinson’s)
• Brain: other degenerative disease
Progressive supranuclear palsy (PSP)
Multisystem atrophy
Olivo-ponto-cerebellar degeneration.
• Copper: Wilson's disease
• Drug induced: antipsychotic
Metoclopramide
• Exogenous toxins: Manganes
• Encephalitis: Post-encephalitic parkinsonism
Pathogenesis: Imbalance between dopamine (↓) and acetyl-choline (↑) in nigrostriatal pathway leads to clinical
manifestations
1. Higher functions: Cognitive dysfunction/Depression
2. Movements:
a. Voluntary:
 Slow to initiate and carry out any activity (bradykinesia)
 Finer movements (which requires precision) are impaired
Ex: Handwriting becomes progressively illegible and small in size (micrographia)
 Activities requiring postural control get impaired: there is a tendency to fall.
b. Automatic movement: Impaired/ lost. Eg: Loss of spontaneous arm swinging during walking
c. Involuntary movement: Tremor:
 Rest tremor: Rest tremor in the hand is often described as ‘pill rolling’/ ’drum beating’, the tremor is
usually marked in the wrist and fingers, which display motion made in the act of rolling a pill. Rest tremor often also
affects ankle and may be seen in the tongue and lower jaw.
 Aggravates when the patient is emotionally upset/ excited
 Decreases in relaxed state/ sleep/ when the affected part is thrown into action.
3. Power: Normal, provided that sufficient time is given to build it up.
4. Tone:
Hypertonia/ rigidity
 Types:
a. Lead pipe rigidity (rigidity> tremor)
b. Cogwheel rigidity (tremor> rigidity).
 Usually the flexors are more hypertonic than the opposite group: this is responsible for the typical attitude/
posture of the patient
 Rigidity (& bradykinesia) of pharyngeal muscle: a. Swallowing difficulty b. Dribbling of saliva.
 Rigidity of laryngeal muscle: Typically monotonous, slow voice without any modulation.
5. Wasting: Absent
6. Reflex: Usually normal
7. Sensory function: Usually normal 8. Sphincter function: normal
8. Gait:
 Difficult to initiate
 Slow velocity: short shuffling gait
 Impaired/ lost arm swing in time of walking
 Tendency to fall and at times, to prevent this fall, patient tries to run towards the destination; leading to
“Festinating gait”
 Difficulty to stop
 Difficulty to turn: the whole body turn around like a statue
9. Facies: Due to rigidity and bradykinesia of facial muscles, face becomes expressionless with infrequent blinking
and staring look, often called “Parkinsonian mask facies”.
Investigation: Clinical diagnosis, however a CT/ MRI of brain is often carried out to rule out any structural lesion.
Treatment
1. Drugs
 L-DOPA+ CARBI-DOPA
 Dopamine releasing agent: Amantadine
 Dopaminergic agonist: Ropinirole/ Pramipexol
 Dopamine metabolism inhibitor
MAO-B inhibitor :Seleziline/Cabergoline
COMT inhibitor:Entacapone/ Tolcapone
 Central anticholinergic:Trihexyphenydyl, Benztropine: Usually used for tremor
a. Surgical
 Thalamotomy
 Pallidotomy
b. Supportive treatment
a. Physiotherapy
b. Walking aids
c. Speech therapy
d. Feeding tube
1. Diseases causing tremor:
a. Parkinsonism
b. Cerebellar disorders
c. Benign familial tremor
2. Parkinsonism plus syndrome:
a. Progressive supranuclear palsy (PSP)
b. Multisystem atrophy/ Shy-Drager syndrome
c. Olivo-ponto-cerebellar degeneration.
Meningitis
Inflammation of meninges.
Causes
1. Pyogenic organism: N.meningitidis, Pneumococcus, Staph.aureus (post neuro-surgical patients), Listeria
2. Tubercular
3. Viral: HSV, Mumps
4. Fungal (in HIV patients): Cryptococcus, Histoplasma
Pyogenic meningitis
Clinical features: often develops acutely
 Fever
with or without ≥ 1 of the followings
 Appetite loss
 Bodyache
 Chill +/- rigor
 Drowsiness/delirium(septic encephalopathy)
 Energy loss
2. Focal/CNS symptoms:
 Headache: Severe, usually gradual in onset and progressively increasing in nature
 Neck pain ± neck stiffness
 Photophobia: prefers to lie with eyes closed/ in a dark room
 Diplopia due to Cranial nerve palsy: 3rd and/or 4th and/or 6th palsy may occur
3. Features of increased ICT:
A. Altered consciousness
B. Behavioral abnormality
C. Confusion, coma, convulsion
D. Delirium
E: Emesis
(F: Papilloedema G: falling GCS)
H: Headache
4. Meningococcemia: Meningococcal rash (due to small vessel vasculitis/ leakage): Typically starts as purpuric/ pin
head spots which may enlarge. These rashes characteristically don’t bleach on pressure (Glass test)
Signs
1. Temperature: High
2. Meningococcal rash: Typically starts as purpuric/ pin head spots which may enlarge. These rashes
characteristically don’t blanch on pressure (due to small vessel vasculitis/ leakage)
3. GCS: May be low Rash: DON’T rely on it!!!
4. Meningeal signs: As OFTEN NOT SEEN EVEN in meningococcal infection
● Neck stiffness/ neck rigidity Not seen in other Bacterial infection
● Kernig sign ● Brudzinski sign (!!!)
5. Signs due to underlying focus of infection: ENT areas/ danger area of face
Investigation
1. Blood: Hb, TC, DC, ESR/ CRP
2. Na+ K+ Urea Creatinine
3. Blood culture and sensitivity
4. CT Brain: To rule out any evidence of raised ICT (which is a relative contraindication to lumbar puncture)
5. Lumbar puncture: CSF study:
WBC: high( often ≥ 100) Protein: > 100 mg/dl CSF: Blood Glucose: < 0.4 Gram stain: may be positive
Predominantly Neutrophil Culture : may be positive
1. Physical appearance: May be turbid
Paired CSF and random blood glucose is checked because IN diabetics,
2. Biochemistry: blood glucose level MAY be high and consequently, CSF glucose level
 Glucose: Normal: Glucose: 45-80 mg/dL will also be high- so even in presence of pyogenic meningitis, CSF
In pyogenic meningitis: ↓↓ glucose may be within the “normal” range. To avoid this the ratio is
taken
Normally In pyogenic meningitis, this ratio often goes <0.4
 Protein: Normal: 20-40 mg/dl In pyogenic meningitis: ↑↑

3. Cytology: Normal WBC: 0-5/μL: In pyogenic meningitis: Leukocytosis is seen, which is neutrophilic in nature.
Often WBC level will go above >100/μL.
4. Microbiological: Gram stain + culture sensitivity: may be positive
Treatment:
Supportive treatment: 1 or more than 1 of the following may be required
A. Absolute bed rest
B. Bed sore prevention
Breathing: Intubation and ventilation if Comatose
C. Catheterization
Circulation by IV fluid
D. Drugs (supportive):
 Antipyretic
 Antiemetic
 Anticonvulsant
 Anti-edema (mannitol)
DVT prophylaxis
Diet: Nutritious diet: NG feed till safe to swallow
Definitive treatment: Empirical antibiotic (IV Ceftriaxone): Usually given for 10-14 days
If Staph. infection is suspected, then add Vancomycin.
Complications
Complications
S Septicemia
Subdural empyema
Seizure
A Abscess of brain
Acute adrenocortical failure/ Waterhouse Friderichsen syndrome (due to adrenal insufficiency
resulting from meningococcal vasculitis: patient suddenly goes into shock)
H Hydrocephalus
Hemiparesis (stroke due to cerebral vasculitis)
Tubercular meningitis
Clinical features
 Fever
with or without ≥ 1 of the followings
 Appetite loss
 Bodyache
 Chill +/- rigor
 Drowsiness/delirium(septic encephalopathy)
 Energy loss
2. Focal/CNS symptoms:
 Headache: Severe, usually gradual in onset and progressively increasing in nature
 Neck pain ± neck stiffness
 Photophobia: prefers to lie with eyes closed/ in a dark room
 Diplopia due to Cranial nerve palsy: 3rd and/or 4th and/or 6th palsy may occur
3. Features of increased ICT:
E. Altered consciousness
F. Behavioral abnormality
G. Confusion, coma, convulsion
H. Delirium
E: Emesis
(F: Papilloedema G: falling GCS)
H: Headache
3. Symptoms of pulmonary TB: +/-
Signs
1. Temperature: High
2. GCS: May be low
3. Meningeal signs:
 Neck stiffness/ neck rigidity
 Kernig sign Examiner: “Do you know what are Kernig/ Brudzinski??”
 Brudzinski sign You: No…SOrry!!
4. Signs of active pulmonary TB +/- Me: I’m SO proud of you!!
Investigations
1. Blood: Hb, TC, DC, CRP/ ESR
3. Blood culture
4. Sputum AFB and mycobacterial culture (if active pulmonary TB is suspected)
5. Chest X Ray
6. CT head:
 To rule out raised ICT
 Tuberculoma may be present.
7. Lumbar puncture (LP): CSF study
WBC: 50-100 Protein: 100-500 mg/dl CSF: Blood Glucose: < 0.4 AFB: May be present
Predominantly Lymphocytic Mycobacterial culture +/-
ADA: High
GeneX-pertTB: M.TB DNA +
Physical appearance: ‘Cobweb coagulum’ may be present

Biochemistry: Paired CSF and random blood glucose is checked because IN diabetics,
Glucose: Normal: Glucose: 45-80 mg/dL blood glucose level MAY be high and consequently, CSF glucose level will
In TB meningitis: Glucose ↓↓ also be high- so even in presence of TBmeningitis, CSF glucose may be
within the “normal” range. To avoid this the ratio is taken
Normally
In TB meningitis, this ratio often goes <0.4
Protein: Normal: 20-40 mg/dl In TB meningitis: ↑↑
Adenosine Deaminsae (ADA): high
Cytology: Normal WBC: 0-5/μL:
In TB meningitis: Leukocytosis is seen, which is Lymphocytic in nature. Often WBC level will go above >100/μL.
Microbiology:
 AFB: May be present
 Mycobacterial culture (BACTEC MGIT method): Often positive
 Rapid detection method: GeneX-pertTB (Nucleic acid amplification)/ RIF (Rifampicin assay):
 Detect M.tuberculosis
 Can detect rifampicin resistance which is a sensitive predictor of MDR-TB.
Treatment
1. Supportive treatment: same as Pyogenic meningitis
 Anti-tubercular drug (ATD): 10-12 months
 Intensive phase: HREZ for 2 months
 Continuation phase: RHE for at least 7-10 months
Dosage: H (5 mg/kg), R (10 mg/kg), E (15 mg/kg), Z (25 mg/kg)
 B Vitamin: B6 supplementation with Isoniazid
 Corticosteroid: Duration: 4-6 weeks (Rationale: To prevent tubercular arachnoiditis and meningeal thickening
so that chance of obstructive hydrocephalus and permanent neurological deficit is minimized)
Complications
1. Obstructive hydrocephalus
2. Stroke/ hemiparesis (resulting from tubercular arteritis)
Brain abscess
A localized area of suppurative infection within the brain.
Risk factor
Although infection may spread to brain from any primary focus of infection in the body, the common risk factors are:
 Ear infection
 Dangerous area of face
 Scalp laceration/ skull injury
 Post neurosurgical patients.
Common organism Streptococcus/ staphylococcus/ anaerobes.
Clinical features
1. Systemic: Fever, malaise, weight loss
2. Features due to increased ICT
3. Primary focus of infection often present.
Investigation
CE-CT of brain
Routine: Hb, TC, DC, CRP, Blood culture
Treatment
Empirical antibiotic: Ceftriaxone IV + Metronidazole(+ Vancomycin if Staph. infection suspected)
Often IV antibiotics may be continued for 4-6 weeks after which they are changed to appropriate oral forms.
Seizure
Seizure: Temporary cerebral dysfunction due to abnormal paroxysmal neuronal (electrical impulse) discharge.
Epilepsy: It is a clinical syndrome characterized by recurrent unprovoked seizures.
Causes of seizure
Provocable causes:
A. ● Alcohol (intoxication/ withdrawal) ● Accident: Head injury: (Post traumatic concussion/contusional injury)
B. Biochemical abnormality:
 Hypoglycemia/ hyperglycemia
 Hyponatremia/ hypernatremia
 Hypercalcemia
 Metabolic encephalopathy (uremic/ hepatic/CO2 narcosis)
 Hypoxic/ ischemic encephalopathy
C. Cerebral causes: ANY patient of seizure…..
 Vascular causes: A “provocable/underlying” cause MUST be looked
 Ischemic stroke for before concluding it to be “idiopathic” BECAUSE
 Hemorrhagic stroke the entire therapeutic approach is often different in
 Intracranial space occupying lesions (IC-SOL) the 2 groups
 Infections:
 Meningitis
 Encephalitis
 Tuberculoma
 Neurocysticercosis
 Brain abscess
D. Drugs (side effect/ intoxication):
 Fluoroquinolone
 Carbapenem
E. Exogenous toxins : Overdose of recreational drugs
No provocable cause:
Epilepsy: Idiopathic
Types of seizure
1. Focal/ partial: abnormal electrical activity arises from one discrete region of one hemisphere
• Simple partial: No loss/ impairment of consciousness
• Complex partial: loss/ impairment of consciousness
• Focal seizure with secondary generalization
2. Generalized: abnormal electrical activity arises from diffuse areas of brain
1. Generalized (abnormal electrical activity arises from a diffuse area of brain)
2. Atonic
3. Myotonic
4. Tonic-clonic (GTCS/ Grand Mal)
Clinical features
Focal seizure: Clinical features of this type of seizure depends on the location of focus of abnormal electrical activity.
Simple partial seizure
1. Motor: Twitching/ jerky movement of a part of the body- which can then spread (“march”) to other parts of body
(Jacksonian movement/march).
2. Somatosensory: Paresthesia: tingling/ pins and needle sensation - can spread to other parts of the body.
 Special sensory manifestations:Visual: Flashes of light
 Auditory: Buzzing noise
 Olfactory: Odd smell
 Gustatory: Odd taste.
3. Autonomic:
 Epigastric fullness
 Palpitation
 Flushing/ sweating
4. Psychiatric manifestations: Illusion/ Hallucination/ Deja-vu
Manifestations usually occur for few seconds to minutes but there is no impairment of consciousness
Complex partial seizure
1. Aura: Motor/ somatosensory/ special sensory/ autonomic/ psychiatric manifestations occur before loss of
consciousness.
However, these manifestations may accompany/ follow the loss of consciousness.
2. Loss of consciousness: Typically lasts for few seconds to minutes,
3. Automatism: Abnormal voluntary activity like lip smacking, repeated swallowing effort, sudden running etc.
4. Recovery: Usually after recovery there is amnesia about impaired consciousness episode.
Focal seizure with secondary generalizations
This may be of 2 types:
1. Simple partial seizure followed by GTCS
2. Complex partial seizure followed by GTCS
Generalized seizures:
Absence seizure
 Typically occurs in children (4-8 years) and usually ceases by the age of 20.
 Clinical features:
 Sudden/ abrupt loss of external awareness: this spell typically lasts for few seconds to minutes and followed
by complete recovery.
 Often occurs in the middle of a conversation, the patient misses a few words/ breaks off in the middle of a
sentence and restart the conversation from where he/she left.
 In some patients, it is accompanied by a tonic/ tonic-clonic movement.
 Patients are not aware about these spells.
Atonic seizure: Abrupt loss of postural tone leading to dropping of head/ sudden collapse/ fall. These patients are at risk
of getting injured.
Myoclonic seizure: Sudden violently forceful contraction of muscles leading to violently disobedient limb.
Generalized tonic clonic seizure (GTCS)
Clinical stages:
1. Tonic stage:
Characterized by generalized rigidity/ spasm of different muscles leading to:
 An abnormal posture (hyper-extended)
 Eyes rolled upwards (ocular spasm)
 Pooling of saliva and frothing (pharyngeal spasm)
 Ictal cry/ a moaning (low pitch) sound (laryngeal spasm)
 Tongue bite (Spasm of jaw)
 A brief spell of respiratory arrest (spasm of respiratory muscles).
- Usually this tonic stage lasts for few seconds to minutes and followed by clonic stage.
2. Clonic stage:
 Abnormal jerky movement of different parts of the body which may be short lasting (seconds to minutes) or may
go on for a while.
 If this continues for a while without any intervening period of recovery of consciousness, it is called “status
epilepticus”.
 If this continues for a while with intervening periods of recovery of consciousness, it is called “serial seizures”.
During tonic-clonic spells, patient usually becomes unconscious
3. Post-ictal period: May last for few minutes to few hours dpending on th e duration of Tonic-clonic stage and
typically characterized by:
 A state of confusion/ disorientation
 Significant headache
 Significant muscle pain
 Patient may develop urinary/fecal incontinence. This is a usually a non-specific symptom.
Investigation (Correlate with the causes of seizure)
1. Blood: Hb, TC, DC, ESR
3. Liver function test
4. Serum Ca++
5. Blood glucose
6. CECT brain (to rule out a structural lesion); if CT is inconclusive, then an MRI may be required.
7. EEG: May be normal/ abnormal.
Treatment
General advice:
 Ensure enough sleep for at least 8 hours a day
 Avoid driving/ swimming/ working with/under heavy machinery
 Monitor the side effects of your medication(s)
Drug treatment:
1st line drug of choice in seizures
• Focal seizure: 1.Carbamazepine/Oxcarbamazepine 2.Lamotrigine 3.Topiramate
• Generalized seizure: Valproate/Divalporex Sodium 2.Lamotrigine 3.Topiramate
• Absence seizure Ethosuximide
2ND line AEDs: a.Gabapentin b.Pregabalin c.Levetiracetam d.Lacosamide

Principles of drug treatment of seizures
When to start?
Idiopathic/ unprovoked seizures: = Secondary/ provoked seizures:
Wait and watch policy: after 1st episode of seizure Treating the underlying cause is OFTEN enough
Long term antiepileptic drugs (AED): in recurrent seizure AED on short term or long term basis depending on
the cause
General principles of treatment?
Start on monotherapy, then gradually increase the dose till the maximum dose is reached/ patient is seizure free
Monitor for side effects/ toxicity
If patient is not seizure free even after taking maximum tolerable dose, then consider starting another 1st line drug/2nd
line drug
If a drug is to be withdrawn/switch over to another drug is required: Gradually increase the dose of the 2nd drug and
gradually taper off the dose of 1st drug
When to stop: AED may be stopped if the patient remains completely seizure free for consecutive 5 years
DD of epilepsy: other conditions with T-LOC

1. Non-epileptic seizure/ pseudoseizure/ functional seizure:
Points to differentiate:Often witnessed
a. Aura absent
b. Convulsive movement often looks unusual
c. Injury rare
d. Tongue bite rare
e. Incontinence rare
f. Hyperprolactinemia absent.
2. Syncope:
a. Pre-monitory/ warning symptoms are different from aura
b. Twitching/ jerky movement, if occurs, doesn’t last for more than few seconds
c. No post-ictal symptoms
d. Tongue bite rare.
e. Background type can be identified from history/risk factor
3. TIA: “Negative symptoms”:
a. Weakness (loss of power)
b. Loss of sensation
c. Loss/Slurring of speech
Status Epilepticus
Repeated tonic-clonic seizures for a while without any intervening period of recovery of consciousness.
C/F: same as GTCS
Investigations Once the seizure is controlled, relevant investigations are to be done to rule out any provocable cause
of seizure- “same as Seizure”
Management
A. Airway: Must be secured. If required apply oropharyngeal suction and intubation.
B. Breathing: Free flow oxygen and ventilation, if required.
C. Circulation: Maintain circulatory volume by IV fluid
D. Drugs:
First Line agents: IV Lorazepam/IV Diazepam/IV Midazolam or Per rectal Diazepam
2nd line agents: IV phenytoin IV FosphenytoinIV Levetiracetam
Refractory cases: 3rd line agents IV phenobarbitone
IV Midazolam Infusion
IV Propofol infusion
Once seizure is under control, long term AED treatment should be considered.
Syncope
Transient loss of consciousness (LOC) due to global cerebral hypoperfusion, where LOC is abrupt in onset, of short
duration and followed by spontaneous complete recovery.
Causes
1. Neurally mediated/ reflex syncope:
A. Vasovagal attack:
Pathogenesis:
I. Vasodepressor response (loss of vasoconstrictor tone, particularly in upright position)
II. Cardio-inhibitory response/ asystole.
B. Situational syncope:
I. Forced micturition
II. Forced defecation
III. Cough syncope.]
C. Carotid sinus hypersensitivity.
2. Cardiogenic causes:
A. Arrhythmia:
I. Brady-arrhythmia: ● Sinus node disease ● AV junction block (Heart block)
II. Tachy-arrhythmia: ● Supraventricular tachycardia (SVT) ● Ventricular tachycardia (VT).
B. Structural heart disease: ● Aortic stenosis (AS) ● Hyperobstructive cardiomyopathy (HOCM).
3. Postural/ orthostatic hypotension:
Causes:
A. Drugs: Vasodilators (antihypertensives)
B. Autonomic neuropathy
C. Volume depletion: Bleeding/ dehydration
Clinical features
A. Prodromal/ warning/ pre-syncopal symptoms:
 Autonomic symptoms (suggestive of vasovagal attack):
 Sweating
 Nausea
 Palpitation
 Paleness of patient
 Blurred vision.
 Postural symptoms (suggestive of orthostatic hypotension):
 Dizziness
 Light headacheness
 Blurred vision.
 Usually no pre-syncopal symptoms (suggestive of transient arrhythmia).
Some patients with warning symptoms can actually prevent the loss of consciousness by taking appropriate defensive
mechanisms. Therefore, these patients often come with pre-syncopal symptoms.
B. Syncopal episode:
 Precipitating factors:
 Prolonged standing (vasovagal)
 Emotional stress:
Bad news/ severe fear/ anxiety/ horrible sight/ smell etc.
 Overcrowded place
 Sudden head turning/ tight collar shirt/ shaving (carotid sinus hypersensitivity)
 Sudden standing (postural hypotension).
 Actual episode:
 Transient loss of consciousness usually lasting never for a period > (10-15) sec.
 Often there is a gap in the memory
 Jerky movements of the limbs (seizure) may occur but is usually very brief and usually occurs
after TLOC
 Momentary urinary incontinence may occur
 Tongue bite extremely rare.
C. Recovery phase: Usually recovery is complete and there is no post-syncopal confusion/ drowsiness.
Signs
 (Lying + standing) BP must be recorded if postural hypotension is suspected
 Ask the patient to stand for 2-3 minutes: A fall of SBP/DBP ≥ 20/10 mm Hg + postural symptoms is suggestive
of postural hypotension
 Proper cardiovascular examination should be carried out to elicit any cardiac abnormality which may cause
syncope (Arrhythmia/AS/HOCM).
Investigation
1. ECG:
1. Resting ECG
2. 24 hours continuous ECG (if transient arrhythmia is suspected and resting ECG is normal)
2. Echocardiogram (to rule out structural heart disease)
3. Carotid sinus massage (to confirm carotid sinus hypersensitivity)
- To be avoided in patients with H/O carotid TIA/ if carotid Doppler shows atherosclerotic plaque.
4. Head tilt test/ Tilt table test (to diagnose neurally mediated syncope)
5. Electrophysiological study: Focus of tachyarrhythmia can be induced, located and ablated, if required.
6. CT head (to rule out any internal bleeding as a consequence of fall).
Treatment
1. Neurally mediated syncope:
Advice the patient:
a. To avoid any triggering/ precipitating factor
b. To take a defensive mechanism during a pre-syncopal symptom
c. Physical counter pressure maneuvers:
I. Continuous limb movement while prolonged standing
II. To sit with crossed legs
III. Simple isometric exercise of the hand (hand-gripping)
d. To drink plenty of fluid
e. Midodrine (α-agonist).
2. Carotid sinus hypersensitivity:
Permanent pacemaker
3. Cardiogenic syncope:
a. Treat the underlying cause
b. Implantable defibrillator in selected cases.
4. Orthostatic hypotension:
a. Treat the underlying cause
b. Avoid sudden standing.
1. TLOC, but not due to global hypoperfusion:
a. Hypoglycemia
b. Primary seizure disorder
c. Vertebro-basillar TIA
2. No TLOC, but transient impaired consciousness:
a. Carotid TIA
b. Cataplexy.
Headache
Primary headache disordres: ● Migraine ● Cluster headache ● Tension headache
Secondary headaches: Headache attributed to any of the following
Head or neck trauma
Cranial vascular disorder
 CVA
 SAH
Nonvascular intracranial disorder
 ICSOL
 Benign Intracranial Hypertension
Infection: Menigitis/ Encephalitis
Substance use or withdrawal: Alocohol
Infection: Menigitis/ Encephalitis
Psychiatric disorder
Migraine
Recurrent severe headache resulting from inappropriate vasodilation of cerebral blood vessels.
Pathogenesis: There is intermittent vasodilation of cerebral blood vessels mediated by different neurotransmitters.
Clinical features
1. Triggering factors:
 Bright light
 Loud sound
 Chocolate/ Caffeine
 Oral contraceptive pills
2. Aura: These are the symptoms which precede/ accompany the headache:
 Visual symptoms:
o Flashes of light
o Zigzag lines
o Tunnel vision.
3. Headache:
 Site: Classically the hemicranium, but may be generalized
 Character: Throbbing
 Intensity: Moderate to severe
 Duration: For several hours
 Accompanied by: Nausea, vomiting
 Patient prefers to lie in closed eye/ in a dark quiet room.
Atypical varieties of migraine
1. Basillar artery migraine (posterior circulation migraine): Headache + focal neurodeficit
2. Ophthalmoplegic migraine: Diplopia + Weakness of extraocular muscles.
Investigation: clinical diagnosis. In severe recurrent headache, a CT head is required to rule out any structural lesion.
Treatment
1. Avoid any triggering factor
2. Acute attack: For emergency/ quick relief
 Analgesic (Paracetamol/ NSAIDS) + Antiemetic
 “Anti migraine” AnalgesicDrug of choice is Sumatriptan
3. Prophylactic/ preventive:
A. Antiepileptic: Topiramate
Amitriptyline
- These 2 drugs are drug of choice.
B. β-blocker: Propranolol
C. Calcium channel blockers: Flunarizine.
Tension headache
Severe recurrent headache often precipitated by stress.
Pattern of headache:
 Site: generalized
 Nature: Band like sensation/ constricting sensation
 Severity: Moderate to severe
 Usually no aura.
Investigation: CT head, if required

Treatment: Acute: Analgesic Prophylactic: ABC (as above).
Cluster headache
Typically occurs in middle aged males.
Pattern of headache:
 Site: Orbital, retro-orbital and temple regions
 Character: Moderate to severe
 Nasal symptoms: Running/ blocked nose
 Ocular symptoms: Watering from eyes/ ptosis/ temporary Horner’s syndrome
 Why the name “cluster”- occurs in spells when the patient develops severe headache which may vary in
severity in different parts of the day and such spells recur almost every day for few days to weeks; then there is a
symptom free period of few weeks after which the next cluster comes.
Investigation:CT head to rule out any structural lesion.
Treatment:
 Acute: ● High flow oxygen (very effective) ●Analgesic ● Sumatriptan
 Prophylactic: ●Verapamil ● Lithium
Brain tumor
Types: 1. Primary 2. Metastatic
Mechanisms of clinical manifestations: due to ≥ 1 of the followings
1. Raised ICT
2. Localizing symptoms and signs (focal manifestations)
3. False localizing symptoms
4. Herniation syndrome
Manifestations due to raised ICT 1 “topic”……..4 “subtopics”!!
A. Altered consciousness  Brain tumor
B. Behavioral disturbances  Raised Intracranial tension
C. Confusion, coma, convulsion  Herniation syndrome
D. Delirium  False localizing sign
E. Etiology: Features due to underlying etiology
For “Short Note” purpose…Answer remains the same…
F. Focal neurodeficit
Brain tumor!!!
Fundoscopy: Papilledema
G. GI manifestations: Nausea, vomiting
GCS may be low
H. Headache
Herniation syndrome
Localizing symptoms and signs (focal manifestations)
Area involved Signs
Frontal lobe  Contralateral UMN signs
(Motor area)  Focal seizures (due to seizures) with motor manifestations
 Aphasia (Broca’s)
 Anosmia (CN1)
 Behavior and personality disturbances
Parietal lobe  Contralateral hemisensory loss
(Sensory area)  Sensory inattention/ neglect (visual/ spatial)
 Contralateral homonymous hemianopia (inf.quadrantic).
Temporal lobe  Focal seizure with somatosensory manifestations
 Psychiatric manifestations
 Contralateral homonymous hemianopia (sup.quadrantic).
Occipital lobe  Contralateral homonymous hemianopia
 Cortical blindness (in case of bilateral compression).
False localizing symptoms In majority of patients, a particular neurological sign indicating pathology at a specific
locus or pathway within the nervous system.
False localizing signs refer to neurological signs that reflect pathology distant from the expected anatomical locus
which make challenges in traditional clinicoanatomical correlation.
A group of clinical manifestations occur in patients with raised ICT (particularly brain tumor) which gives an
erroneous impression about the site of the lesion:
 CN6 palsy (as it has the longest intracranial course)
 CN3 palsy
 Bilateral extensor plantar (resulting from brainstem compression)
 Ipsilateral upgoing plantar (resulting from compression of cerebral peduncle against tentorium).
Herniation syndrome
If there is raised ICT, a part of the brain sometimes escape through a foramen towards a low pressure compartment.
This commonly occurs with cerebellum, which herniates through foramen magnum; leading to brainstem (particularly
medullary) compression- causing:
1. Cardio- Respiratory arrest
2. Deep coma
Investigation
1. CE-CT Brain
2. If CT is abnormal: MRI brain
Treatment
1. Propped up positioning
2. Anti-edema drugs:
 IV mannitol (for 3-5 days) followed by oral glycerol
 Steroid
3. Analgesic
4. Antiemetic
5. Anticonvulsant (if seizure occurs)
6. Surgical:
 Ventriculo-peritoneal shunt (in case of obstructive hydrocephalus)
 Craniotomy flap (in a stroke patient with severe edema).
7. Elective ventilation with permissive hyperventilation (hypocapnia will induce cerebral vasoconstriction and
therefore ICT will be reduced).
Definitive treatment:
1. Surgical excision of brain tumor
2. Radiotherapy
3. Chemotherapy.
Delirium
Transient, usually reversible, cause of cerebral dysfunction and manifests clinically with a wide range of
neuropsychiatric abnormalities.
Diagnostic criteria for delirium is as follows
Attention deficit-reduced ability to direct, focus, sustain, and shift attention.
Behavioral dyscontrol
Cognition disturbance- memory deficit/disorientation/language disturbance/perceptual disturbance
Duration-develops over a short period (usually hours to days)
Evidence from the history, examination, or lab findings that the disturbance is caused by a direct physiologic
consequence of a general medical condition, an intoxicating substance, medication use, or more than one cause
Fluctuates during the course of the day.
Types
Hypoactive
Hyperactive
Mixed
Causes
A-Alcohol Intoxication/Withdrawal
B-Biochemical disturbance-
 hypo or hyperglycemia/Hypo or hyper Na/HyperCa
 Renal failure/Liver failure/CO2 retention
 Hypoxia
B-Bacterial Infection- any severe infection
C-Cerebral- CVA/ CNS infections/Subdural
Hematoma/SAH/ICSOL
D- Drugs
D-Dementia
E-
Environmental- unfamiliar environment- particularly in elderly
Endocrinopathies- Hypothyroid
Investigations- Not all patients will need each of these tests

FBC, ESR/CRP
Ur + Cr+ Na+ K+ Ca- To diagnose Renal impairment/Dyselectrolytemia
Glucose - To diagnose hypoglycemia/DKA/HHS
LFT - To diagnose liver failure
TFT - To diagnose hypothyroidism
Urine analysis - to diagnose urinary tract infection
Urine and blood drug screen -to diagnose toxicological causes
Tests for bacteriological and viral etiologies - To diagnose infection
Drug screen including alcohol level
CT scan of the head
Treatment- An underlying causes should be sought and addressed/treated
Delirium and Dementia
Features Delirium Dementia
Onset Acute Insidious
Course Fluctuating Progressive
Duration Days to weeks Months to years
Consciousness Altered Clear
Attention Impaired Normal, except in severe dementia
Psychomotor changes Increased or decreased Often normal
Reversibility Usually Rarely
Rest of the CNS is for “Short Notes Lovers”!!
All the best!!!

Involuntary movements
Tremor
It is a rhythmic oscillatory movement of different parts of the body due to repeated contractions and relaxations of a
group of muscles.
Classification/ types
Depending upon frequency: 1.Fine 2. Medium 3.Coarse
Depending upon activity 1.Rest 2.Intention 3.Postural
Postural tremor: Usually occurs when tremulous part of the body is kept in a sustained posture.
Intention tremor: Tremor increases while attempting to execute a voluntary activity.
Causes
Type Causes
Fine/ intention/ postural A. Alcohol excess/ withdrawal (chronic)
B. Benign essential tremor
C. Cigarette smoking
D. Drugs: β2 agonist
E. Endocrinopathy: Thyrotoxicosis.
Medium/ coarse/ rest  Parkinsonism
 Cerebellar lesion
Clinical features
 Affected part of the body shows tremor: type and aggravating factor of which depends on the underlying disease
 Specific features of the underlying disease.
Investigation
1. TSH
2. Relevant investigations to assess the underlying disease
Treatment: 1.Stopping of any triggering factor 2. Treatment of the underlying disease/casue
Benign essential tremor

History: Family history of tremor usually present.
Clinical features:
Description of tremor:
 Bilaterally symmetrical
 Fine tremor
 Usually affects upper limbs, head, tongue but usually spares trunk and lower limbs
 Aggravated by stress
 Temporarily relieved by alcohol
Treatment:
 Drug of choice: Propranolol
 If fails: Primidone.
Chorea
It is an abnormal involuntary movement characterized by non-repetitive jerky movement particularly affecting the
extremities.
Site of lesion: Caudate nucleus
Causes:
1. Sydenham’s chorea
2. Huntington’s disease
3. Wilson’s disease
4. Chorea gravidarum.
Athetosis
It is an abnormal movement characterized by slow sinuous, often fine movement particularly affecting the extremities.
Site of lesion: Putamen
Causes: ●Wilson’s disease ● Perinatal hypoxia ●Kernicterus.
Fasciculation
Abnormal twitching movement involving few muscle fibres.
Types
• Fasciculation Physiological: When the muscle is exhausted
• Pathological: Denervating lesion particularly affecting AHC/ CNN- Motor neurone disease/ Polio
Cause of reversible dementia
Alcohol abuse
‘B’ Vitamin deficiency- B12/Folate/B1
Biochemical disturbances
1. Hypo/hyper Ca
2. CLD
3. CO2 retention
Chronic Subdural hematoma
CNS infection
Drugs** and toxins
Endocrinopathy- Hypothyroid/Pituitary insufficiency/Addison’s
Epilepsy
Dementia
It is a state of cognitive impairment which is usually slowly progressive and often causes social and occupational
dysfunction.
Causes
Reversible Irreversible
Alcohol abuse** Alzheimer's disease
‘B’ Vitamin deficiency- B12/Folate/B1 Fronto-temoral dementia
Biochemical disturbances Lewy body dementia
Hypo/hyper Ca Normal pressure hydrocephalus
CLD Progressive supranuclear palsy
CO2 retention
Chronic Subdural hematoma**
CNS infection
Drugs and toxins
Endocrinopathy- Hypothyroid/Pituitary insufficiency/Addison’s
Epilepsy
Clinical features
1. Short time memory loss
2. Inability to name an object (nominal aphasia)
3. Visuo-spatial dysfunction: ● Inability to navigate ● Gets lost in a known surrounding
4. Executive dysfunction: ● Easy distractibility ● Lack of concentration
5. Along with these manifestations, patients often become delirious
6. Patient often develops apathy (indifference to others)
7. Specific signs and symptoms of the underlying disease
8. “Mini-mental state examination” score: low
Investigation
1. Dementia screen:
a. Blood: Hb, TC, DC, CRP/ESR
b. Serum vitamin B12
c. Serum TSH.
2. CT head.
Treatment
1. Non-pharmacological management: Family and social support
2. Pharmacological management:
a. Treatment of any reversible cause
b. For dementia “Syndromes”:
Anticholinesterase: ● Donepezil ● Rivastigmine
NMDA receptor blocker: ● Memantine.
Multiple sclerosis (MS)
It is an autoimmune inflammatory demyelinating disease of the nervous system.
Etiopathogenesis:
In genetically predisposed individuals, an autoimmune response triggers off the demyelinating process.
Environmental factors probably play some role.
Clinical course: Depending on the clinical course, MS is classified into 3 types:
● Relapsing-remitting type ● Primary progressive type ● Secondary progressive type.
Clinical features:
1. Higher function:
 Cognitive dysfunction
 Depression.
2. Cranial nerves:
 Optic neuritis
 Trigeminal neuralgia
 Internuclear ophthalmoplegia (On attempted lateral gaze, there is a failure of adduction and nystagmus
of the abducting eye, cause: damage of median longitudinal fasciculus)
3. Motor: Weakness- May affect one/ multiple limbs. There is marked spasticity with UMN signs.
4. Sensory:
 Patient may complain of numbness, tingling, paresthesia of different parts of body.
 Sensory impairment
 Lhermitte's sign: Electric shock like sensation passes down the spine on attempted neck flexion.
5. Cerebellum: Cerebellar signs may be present.
6. Sphincter: Sphincteric disturbances are common (retention and incontinence).
7. Trophic changes: As many of these are completely bed ridden, they may develop bed sore, trophic ulcer etc.
Investigation:
1. MRI of brain and spine: Visualizes the demyelinating lesion (Plaque).
2. Lumber puncture: CSF shows markedly elevated IgG (Oligoclonal band of IgG).
Treatment:
1. Supportive:
a. Bed sore prevention
b. Catheterization
c. Daclofen: For spasticity.
d. Exercise and physiotherapy
2. Drugs:
a. Corticosteroid:
 In acute flare: IV Methylprednisolone
 Chronic phase: Oral corticosteroid.
b. Immunomodulators:
 Glatiramer acetate
 Natalizumab
 IV IgG/ Plasmapheresis may be effective during acute relapse.
Pontine hemorrhage
Pontine hemorrhage is a type of brainstem hemorrhage which is a serious medical condition that can often lead to
coma and death.
Causes
Arterial hypertension
Aneurysm rupture
Bleeding disorders
Brain injury/head injury
C/F- may vary depending on amount of bleed.
1. Autonomic disturbance- Hyperventilation/Abnormal breathing pattern/Pin point pupil/Hyperpyrexia
2. Brain stem cranial nerves sign- 6th/7th nerve palsy
3. Contralateral Hemiparesis/ Quadriparesis(→Pyramidal fibers of both sides are very close to each other)
4. Coma- may be very deep
5. Conjugate Gaze palsy- Persistent conjugate deviation towards paralytic side
( Rememeber PONS lesion = Paralytic or Normal side, MID brain lesion= Mobile/Diseased side)
Investigations-
CT Brain
Treatment
A.airway
B.Breathing…../Bed sore prevention
C.Circulation…../Catherterisation
D.Drugs: Antihypertensices/Diet- oral/through R. Tube/DVT prevention- DVTstocking (NOT heparin, as Hgic pt)
E. Exercise= Physiotherapy
Pronator Drift
Pronator drift (pyramidal drift) refers to a pathologic sign seen during a neurological examination. This sign can
appear due to an upper motor neuron lesion
The patient is asked to hold both arms fully extended at shoulder level in front of them, with the palms upwards, and
hold the position. If they are unable to maintain the position the result is positive. Closing the eyes accentuates the
effect, because the brain is deprived of visual information about the position of the body and must rely
on proprioception.
UMN dysfunction will cause the weak arm to PRONATE and DRIFT DOWNWARD, since UMN pattern of weakness
results in supination in the upper extremities being weaker than pronation (i.e. the pronator drift).
Interpretation
This is a test of upper motor neuron disease.
If a forearm pronates, with or without downward motion, then the person is said to have pronator drift on that side
reflecting a contra-lateral pyramidal tract lesion
Pseudotumor cerebri/ Benign intracranial hypertension (BIH)
It is a condition characterized by raised ICT where the underlying cause is innocuous.
Causes
1. Idiopathic (common in young obese females)
2. Drugs:
a. Long term vitamin A derivatives (Ex: Retinoid)
b. Tetracycline
c. OCP
Clinical features
 Often patients are obese
 H/O offending drug intake
 Signs and symptoms of raised ICT (ABCDEFGH as describe above)
Investigations
5. CE-CT Brain:
Findings:
 Signs of raised ICT
 No structural lesion
 Ventricular system not dilated.
6. LP (do very cautiously):
High CSF pressure; other findings are normal.
Treatment
1. Encourage to lose weight
2. Stop offending drugs
3. Acetazolamide tablet (Carbonic anhydrase inhibitor)
4. Therapeutic lumbar puncture.
Polymyositis
Polymyositis is an idiopathic inflammatory myopathy that causes symmetrical, proximal muscle weakness.
Polymyositis and Dermatomyositis is an idiopathic, inflammatory myopathy associated with characteristic
dermatologic manifestations.
C/F
Skeletal muscle-
Symmetrical, predominantly proximal muscle weakness in the upper and lower extremities with pain +/- tenderness.
Muscle weakness may fluctuate from week to week or from month to month.
Distal muscle/ Fine movements eg. buttoning a shirt, sewing or writing are affected late in the disease.
Ocular/Facial/bulbar muscle weakness- extremely rare
Oro-pharyngeal/Oesophageal muscles- Dysphagia+/- aspiration pneumonia
Respiratory muscles- SOBE due to weakness of chest wall & diaphragmatic muscles
Cardiac muscle involvement- unusual
Systemic symptoms- Morning stiffness; Fatigue; Anorexia; Weight loss
Investigations
ESR/ CRP - Elevated in many
Elevated muscle enzyme level- CK; Myoglobin
Autoantibodies-Antisynthetase antibodies/ anti-Jo-1 antibodies
Electromyography- abnormal in almost all
Muscle biopsy is crucial in helping to diagnose polymyositis and in excluding other rare muscle diseases
Rx
1. Corticosteroids- 1st line Rx
2. Immunosuppressants (2nd line Rx)- Azathioprine/ Cyclophosphamide/ Chlorambucil/ Cyclosporine
3. Physiotherapy
Romberg Sign
Romberg's test is done to assess the integrity of the dorsal columns of the spinal cord. It is not a test to assess the
cerebellar function.
Patient is asked to stand with feet firmly together, arms by the side and the eyes open at first. The balance of the
patient is noted. Now the patient is asked to close both eyes and the balance is now noted for a while.
Interpretation
1) If with the eyes open, the balance is not good then there may be a problem with the cerebellum.
2) If closing the eyes causes a much worse balance then the test is said to be positive (Romberg test positive). The
problem may lie in the vestibular or proprioceptive systems.
To maintain balance at least 2 of 3 components are needed : 1) vision 2) proprioception 3) vestibular function.
If a patient has a vestibular problem then with his eyes open he can maintain balance because proprioception and
vision is helping. But now if he closes his eyes, then there is only proprioception to maintain balance and that is not
sufficient. So the patient will sway and may fall.
The same is true for someone with a problem of proprioception. With his eyes open, the patient can maintain balance
because he is using his normal vision and vestibular apparatus. But when he closes his eyes, he is only relying on his
vestibular function now and thus he will sway and may fall.
Common causes of positive Romberg test:
1) Vitamin B12 deficiency - Subacute combined degeneration of the cord
2) Diabetic peripheral neuropathy
3) Friedrich's ataxia
4) Tabes dorsalis
Pin point pupil

Constricted pupil which is 1-2mm in diameter
Causes
Brain stem hemorrhage
Brain stem herniation/peduncle/tonsils
Drugs: Barbiturate overdose; Opiates/Narcotics toxicity
Poisoning: Insecticide/Organophosphate toxicity
Meiotic eye drop!!!
Clinical Approach- following things are to be looked for in such a patient
h/o overdose of drugs
h/o Organophosphate ingestion
Evidence of brainstem stoke/injury: Paralysis/Cr. Nerve. Signs/Coma/loss of doll’s eye
Evidence of OP poisoning- ‘’SLUD’’: salivation/lacrimation/urination/diarrhoea
Evidence of Opiate toxicity- Respiratory depression
Investigations
CT Brain
Toxicology screen- Blood/urine OP/Opiate level
Treatment- depends on the cause
OP poisoning- Atropine +/-
Opiate toxicity- Naloxone
Acute monocular vision loss
Causes
1. Amaurosis Fugax (occurs in TIA) 5. Branch Retinal Artery/Retinal Vein Occlusion
2. Optic Neuritis 6. Central Retinal Artery/Vein Occlusion
3. Anterior Ischemic Optic Neuropathy 7. Intraocular Foreign Body
4. Bacterial Endophthalmitis 8. Acute glaucoma
C/F- these give important clues regarding the underlying cause
History
History Examination
Duration of visual loss Inspection of the extraocular area
History of trauma Visual acuity
Prior episodes/ophthalmologic history Extraocular movements
Symptoms - Photophobia, headache, pain Pupil reactivity including RAPD
Comorbid conditions- ● Hypertension ● External appearance
Hypercholesterolemia Intraocular pressure
Visual field testing
Fundus examination
Cardiac and CNS examination including murmurs and
carotid bruits
Investigations
FBC
Atherosclerosis risk stratification- FBS/PPBS/Lipid profile
Echocardiography
Carotid Doppler
Fluorescein angiography
Treatment- Depends on the cause
1. Opthalmological
2. Medical:
 Amaurosis fugax- Aspirin + (Dipyridamole OR Clopidogrel)
 Optic neuritis high- dose intravenous methylprednisolone
3. Surgical- Amaurosis fugax with a carotid stenosis of 70% or greater Carotid endarterectomy
Carpal tunnel syndrome

CTS is an entrapment neuropathy due to compression of the median nerve within the carpal tunnel.
Causes
Acromegaly Myxedema
Amyloidosis Rheumatoid arthritis
Diabetes Wrist fracture (Colles)
C/F
1. Numbness and tingling in the palmar aspect of the 1st to 4th fingers and the distal palm (ie, the sensory distribution
of the median nerve). Nighttime symptoms that wake the individuals is often prominent.
2. Pain- an aching sensation over the ventral aspect of the wrist which radiates distally to the palm and fingers
3. Weakness/clumsiness - Loss of power particularly for precision grips involving the thumb
4. Sensory Abnormalities- present on the palmar aspect of the first 3 digits and radial one half of the fourth digit.
5. Motor - Wasting and weakness of the median-innervated hand muscles (LOAF muscles) may be detectable.
6. Special tests - No good clinical test exists to support the diagnosis.
a. Tinel sign-Tapping over the median nerve in the carpal tunnel region elicits tingling in the nerve's distribution.
b. Phalen sign-Tingling in the median nerve distribution is induced by full flexion of the wrists
Investigations
1. Electrophysiologic studies- EMG+ NCV, are the first-line investigations
2. Blood tests to look for an underlying cause
Treatment
For Pain- Pregabalin/Gabapentin/Amitryptilline
Therapeutic ultrasound
Splinting the wrist at night time for a minimum of 3 weeks.
Surgical release of the transverse ligament
Aseptic meningitis
Aseptic meningitis is characterized by serous inflammation of the meninges usually with an accompanying
mononuclear pleocytosis in CSF.
[
Etiology:
Acute viral infection is the most common cause: Enteroviruses/Herpes/Mumps/HIV
Bacterial: Partially treated Pyogenic meningitis
Brucellosis
TB
Bechet disease
Connective tissue disease: SLE
Drug induced
Clinical manifestations: vary, with headache and fever predominating. The illness is usually mild and runs its course
without treatment; however, some cases can be severe and life threatening.
Meningeal signs: mild-moderate neck stiffness
Investigations:
CT brain
CSF study: typically shows: High protein+ mildly reduced or normal Glucose+ Lymphocytosis
Microbiological tests may demonstrate the organism if etiology is an infective one
Treatment:
Specific: Antimicrobial agents in cases of an Infective etiology
Supportive: depending on the clinical scenario
Antipyretic
Analgesic
Antiemetic
Anticonvulsant
Ring lesion in CT
A ring-enhancing lesion is an abnormal radiologic sign on MRI or CT scans obtained using radiocontrast. On the
image, there is an area of decreased density surrounded by a bright rim from concentration of the enhancing contrast
dye
The differential for ring enhancing cerebral lesions includes:
Abscess
Brain metastasis
Cancer:
 Primary: any primary malignancy of brain
 Lymphoma – typically in immunocompromised patient
CVA: subacute infarct / haemorrhage
Cysticercosis: Neurocysticercosis
Demyelination (incomplete ring)
Effects of radiation treatment: Post radiation necrosis
Granulomatous disease: Tuberculoma

Letuda 2020

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Letuda’s Note 2020

Visible/Obvious loss Invisible/Occult loss Visible/Obvious loss Invisible/Occult loss

4. Tissue: Biopsy/ FNAC

Infection related BLOOD tests

Inflammmatory response Microorganism in the bloodstream

HIGH “inflammatory markers” “Capturing” Microorganism

Brain: CSF Utility of “regional material” tests

PET-CT scan whole body

Metabolically ACTIVE tissues EXCESSIVELY uptake this glucose

Non invasive technique/tests Invasive technique/tests

2 very common diseases that radio-imaging appearance helps to diagnose

Infective pathology Tumor (benign/malignant)

Infective etiology Non- infective etiology Benign Malignant

ALL CONFIRMED BY following 2 tests of biopsy/FNAC sample

Overproduction of Overproduction or Under-excretion Excessive wash out of Excessive loss of

Gastrointesinal (includes hepatobiliary)

Peripheral smear: Morphological abnormality of Blood corpuscles: “MOST VALUABLE” investigation

abnormality of RBC abnormality of WBC abnormality of Platelet

Cellularity Cell surface Markers Cytogenetic

E Bed sore (pressure ulcer) prevention

Means of DVT prevention:

No sound= impaired/dull “More” sound= hyperresonant/tympanitic

No air: Collapse/Fibrosis/Consolidation Increased air content

Airway remodelling “Physical” obstruction

Secretion Exudate Hemorrhage Pulmonary edema

Bronchiectasis Pneumonitis Alveolar hemorrhage “squeezed out” “oozed out”

Pneumothorax  Often no shift Entire hemithorax of the affected side

COPD No shift bilateral symmetrical

S3 (also called Ventricular gallop) S4 (also called Atrial gallop)

Streamline flow No murmur “power” of Turbulence enough to become “audible”

So turbulent flow present‐ BUT murmur NOT ALWAYS audible!!

Organic murmur Flow/ Innocent/ functional murmur

Heart failure drugs

Drugs used in IHD

Valvular & Congenital Heart diseases: overview

Incomplete opening: Stenosis Congenital Valvular defect Nonvalvular defect

Pressure overload Volume overload

Cardiac failure Tachyarrhythmias

Left heart Right heart Atrial origin Ventricular origin

Rx of Heart failure Rx of Arrhythmia Rx of Endocarditis Cardiac surgery

Valvular Heart disease Congenital HD

Valve replacement Correction of the defect

Prosthetic(artificial) valve technique

FOR EACH OF THESE Clinico- investigation picture shows

Evidence of Hemolysis & its effects “Unique” or “Special” effect

Clinical manifestations of Hemolytic diseases: ≥ 1 of the followings:

Due to vessel wall defect Platelet defect Coagulation pathway defect

Rare Quantitative deficiency Qualitative defect Deficiency of Coagulation factors

So ignore!! Thrombocytopenia Defective Pl. function Reduced synthesis Overconsumption

Part of Pancytopenia Isolated thrombocytopenia Inherited diseases Acquired conditions

Clinical features: of ANY bleeding disorder patient

Solid tumor Liquid tumor

Loco-regional effects Distant effects

Disease directed treatment Palliative treatment

Curative intention Disease downsizing/downgrading intention

Called Neoadjuvant therapy Called Adjuvant therapy

Proliferation + Maturation arrest Proliferation without maturation defect

Acute Leukemia Chronic Leukemia

Bone marrow Infiltration: Normal marrow cellular population is replaced by Leukemic

2. Due to organ infiltration:

Tests to detect complications/ overall assessment of patient:

Leukemia: Investigation summary

1. Medical BMT/Stem cell transplantation