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Table of Contents
1. Neurology ................................................................................................................................ 6
Functional neuroanatomy................................................................................................................... 6
Localization of cerebral cortex ............................................................................................................ 6
Cranial nerve palsy .............................................................................................................................. 8
Strokes .............................................................................................................................................. 16
Spinal cord disease............................................................................................................................ 27
Nervous System Infection ................................................................................................................. 31
Muscle disease .................................................................................................................................. 36
Neuromuscular junction disorders ................................................................................................... 37
Movement disorders......................................................................................................................... 39
Neuropathies .................................................................................................................................... 41
Headache .......................................................................................................................................... 43
Brain Tumours ................................................................................................................................... 50
2. Kidney diseases ...................................................................................................................... 53
Glomerular diseases.......................................................................................................................... 54
Tubular interstitial nephritis ............................................................................................................. 70
UTI ..................................................................................................................................................... 71
Chronic Kidney disease ..................................................................................................................... 73
Acute kidney injury ........................................................................................................................... 74
PCKD .................................................................................................................................................. 78
Renal tubular acidosis ....................................................................................................................... 79
3. Endocrinology ........................................................................................................................ 80
Hypopituitarism ................................................................................................................................ 80
Thyroid axis ....................................................................................................................................... 83
Hypothalamo-pituitary-adrenal axis ................................................................................................. 91
Hypothalamo-pituitary-gonadal axis ................................................................................................ 98
Thirst axis ........................................................................................................................................ 101
Calcium Metabolism ....................................................................................................................... 107
Diabetes mellitus ............................................................................................................................ 111
4. Haematology........................................................................................................................ 129
Anaemia .......................................................................................................................................... 129
Haemostatic Disorders and coagulation disorders ......................................................................... 133
Disorders of Platelet ....................................................................................................................... 135
Leukaemia ....................................................................................................................................... 135

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 Lymphoma ...................................................................................................................................... 137
Multiple Myeloma........................................................................................................................... 137
Myeloproliferative disorders .......................................................................................................... 138
Blood transfusion ............................................................................................................................ 138
Anticoagulants ................................................................................................................................ 139
5. Rheumatology and Bone Diseases ........................................................................................ 141
Shoulder Pain .................................................................................................................................. 141
Osteoarthritis .................................................................................................................................. 142
Rheumatoid Arthritis ...................................................................................................................... 144
Spondyloarthritis (SpA) ................................................................................................................... 148
Gout ................................................................................................................................................ 150
Septic Arthritis ................................................................................................................................ 151
SLE ................................................................................................................................................... 152
APLS................................................................................................................................................. 155
Systemic Sclerosis ........................................................................................................................... 156
Polymyositis and Dermatomyositis................................................................................................. 157
Overlap syndrome........................................................................................................................... 157
CPK levels ........................................................................................................................................ 157
Side effects of drugs........................................................................................................................ 158
Systemic vasculitis........................................................................................................................... 159
Giant Cell Arteritis and Polymyalgia Rheumatica ........................................................................... 160
Still’s disease (aka systemic onset JIA) ............................................................................................ 161
Osteoporosis ................................................................................................................................... 162
Osteomalacia .................................................................................................................................. 163
6. Hepatology .......................................................................................................................... 165
Clinical approach to the patient with liver disease......................................................................... 165
Jaundice .......................................................................................................................................... 167
Viral Hepatitis.................................................................................................................................. 172
Acute liver failure ............................................................................................................................ 175
Autoimmune hepatitis .................................................................................................................... 177
Cirrhosis .......................................................................................................................................... 177
7. GI Disorders ......................................................................................................................... 196
Acute diarrhea ................................................................................................................................ 196
Chronic Diarrhoea ........................................................................................................................... 198
Inflammatory Bowel Disease .......................................................................................................... 201
8. CVS ...................................................................................................................................... 206

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 Examination of the CVS................................................................................................................... 206
Hypertension................................................................................................................................... 208
Coronary artery disease .................................................................................................................. 215
Cardiac arrhythmias ........................................................................................................................ 222
Infective endocarditis ..................................................................................................................... 241
Valvular disorders ........................................................................................................................... 245
Pericardial disease .......................................................................................................................... 250
Myocardial and Endocardial disease .............................................................................................. 254
Heart failure .................................................................................................................................... 255
9. Respiratory diseases ............................................................................................................. 266
Lung function tests.......................................................................................................................... 266
Respiratory tract infections ............................................................................................................ 267
Asthma ............................................................................................................................................ 269
COPD ............................................................................................................................................... 273
Pneumothorax ................................................................................................................................ 278
Tumors of the respiratory tract ...................................................................................................... 282
Bronchiectasis ................................................................................................................................. 286
Interstitial Lung Disease (Diffuse parenchymal lung disease) ........................................................ 287
Venous Thrombo-Embolism (VTE) .................................................................................................. 289
Pulmonary hypertension................................................................................................................. 294
Respiratory system Drugs .............................................................................................................. 296
10. Toxicology .......................................................................................................................... 299
Management of acute poisoning .................................................................................................... 299
Snake bites ...................................................................................................................................... 304
11. Infections ........................................................................................................................... 307
Brucellosis ....................................................................................................................................... 307
Leprosy (Hansen’s disease) ............................................................................................................. 307
Enteric fever .................................................................................................................................... 308
Typhus ............................................................................................................................................. 309
Melioidosis ...................................................................................................................................... 310
Candidiasis ...................................................................................................................................... 310
Malaria ............................................................................................................................................ 311
Leishmaniasis .................................................................................................................................. 312
Toxoplasmosis ................................................................................................................................. 313
Amoebiasis ...................................................................................................................................... 313
Varicella (chickenpox) ..................................................................................................................... 314

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Dengue ............................................................................................................................................ 314
Zika virus infection .......................................................................................................................... 315
Infectious mononucleosis: Epstein–Barr virus infection................................................................. 316
Poliomyelitis .................................................................................................................................... 316
Rheumatic fever .............................................................................................................................. 317
Bacterial meningitis ........................................................................................................................ 320
Gastroenteritis ................................................................................................................................ 321
Invasive staphylococcal infection ................................................................................................... 324
GU Infections .................................................................................................................................. 325

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1. Neurology
Functional neuroanatomy
Neuron is the functional unit of the nervous system, the size and the type of each neuron vary

Neurotransmitters could be

 Excitatory : acetylcholine, noradrenaline, adrenaline, glutamate, aspartate

 Inhibitory : GABA, histamine, glycine,
 MIxed : ACTH, vasopressin, ATP, AMP

Localization of cerebral cortex

Dominant hemisphere

Usually left (all right handed and 70% of left handed has their language function in the left)

Aphasia

Broca’s Aphasia Wernicke’s Aphasia Nominal aphasia Global aphasia

Reduced fluency Fluency preserved with Inability in naming Fluency reduced

muddled words

Relatively preserved incomprehensible incomprehensible

comprehension

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 Problem in initiation of No problem in speech Speech initiation
speech initiation hindered

Telegrammatic speech Jargon speech with

with few words but inappropriate words
failed sentence mistaken for psychosis
structuring

Damaged left cerebral Left temporal parietal Combination in both

cortex area damaged Broca and Wenicke
area

Dysarthria

 Disordered articulation - slurred speech

 Paralysis, slowed or incoordination of muscles
Examples

1. Gravelly speech in pseudobulbar palsy

2. Jerky ataxic speech of cerebellar speech
3. Hypophonic montonic speech in Parkinsons
4. Speech in mysthenia that fatigues and dies away

Memory and its disorders

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Cranial nerve palsy
Optic nerve
Types of lesions

1. Hemi anapoic
2. Quadranaopic

 Lesions posterior to the optic chiasm

produce homonymous field defects
 Lesions damaging decussating nasal fibres
at the optic chiasm cause bitemporal
defects.

Optic nerve lesion

 The hallmark of the lesion would be a

scotoma, central or paracentral
 Most fibers of the optic nerve provide
macular vision
 Examination findings in optic neuropathy
1. Reduced acuity

2. Scotoma

3. Reduced colour vision

4. Afferent pupillary defect

5. Optic atrophy- pale disk, late sign

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Papilloedema

 Swelling of the disk

 Earliest sign : disk pinkness, blurring at disk margins usually at nasal regions
 Loss of pulsation in retinal veins in the disc
 Small haemorrhages are visible usually
 Marked hypermetropy make disc appear pink
 Myelinated nerve fibers at margins with hyaline bodies could be mistaken for disc swelling
 Disc infiltration in leukaemia causes papilloedema
 Papilloedema produces less visual symptoms, usually momentary loss of vision with changes in
posture
 Blind spot is enlarged but not noted by patient
 Gradually there's optic atrophy

Optic neuritis

 Usually due to infective or inflammatory causes

1. Sarcoidosis

2. Vasculitis

 Causes subacute loss of vision

 Mild fogging of central vision with colour desaturation
 Complete blindness is rare
 Pain in eye movements is universal
 Found by MRI (can be even due to developing MS with conferred lesions)
 Recovery usually in months, enhanced by high dose IV steroids at acute stage

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Anterior ischemic optic neuropathy

 Supplied by posterior ciliary arteries

 Sudden or stuttering visual loss
 Hypermetropic discs are predisposed
 Vascular risk factors e.g. arteritis plays an important role in aetiology

Optic atrophy

 Disc pallor is seen with loss of axons, glial proliferation and decreased vascularity
 Usually follows any type of optic neuropathy

Pupils

Physiologic anisocoria - difference in pupils of 1 mm and doesn’t vary with light

Anisocoria is pronounced and convergence is sluggish in senile age

Afferent pupillary defect

Complete damage to optic nerve

 Pupil does not respond to light, direct reflex is absent

 Consensual reflex is absent in the defected side but the consensual reflex of the unaffected side
stays intact
Relative Afferent pupillary defect

 Due to incomplete damage to optic nerve relative to the other

 Very sensitive sign, can be present even after recovery
 Direct and indirect reflexes are present in both eyes but in different in relative strength
 The affected eye usually shows less dilation and constriction (consensual is usually stronger
than direct)

Horner’s syndrome

Clinical features

1. Unilateral miosis

2. Partial ptosis

3. Loss of sweating in
ipsilateral part of the face

4. Subtle conjuctival injection

and enophthalmus

Miosis is seen well in dim light

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Occulomotor, trochlear and abducens nerve

Eye movement control

 Fast movements originated in frontal lobes

 Fibers descend and cross to enter the pons (paramedian pontine reticular formation (PPRF)) for
lateral gaze
 Ipsilateral occipital cortex is involved in tracking objects
 The vestibular nuclei involved in eye movements with position of head and neck
 Conjugated lateral eye movements coordinated by PPRF and medial longitudinal fasciculus
(MLF)
 Fibers of PPRF goes to ipsilateral 6th nuclei and to opposite third nuclei

Abnormalities in conjugate lateral gaze

There are two types of lesion

1. Lesion at PPRF lead to eyes beign not able to show conjugate gaze to same side

2. Lesion at the frontal cortex (probably due to infarct) causes eyes being deviated to normal side
acutely, and failure of lateral conjugate gaze to contralateral side

Eg lesion in left causes disability in conjugate gaze to right

It is usually associated with contralateral hemiparaseis

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Internuclear ophthalmoplegia

Lesion is at MLF

 E.g. Lesion of the right MLF causes inability of

the right eye to adduct or could be slow in the
specific movement
 Side of the lesion is at the eye which cannot
adduct
Bilateral INO is pathognomic for MS

One and a half syndrome

This is a lesion both at PPRF and MLF

Defective upward gaze also develop in degenerative

diseases

Nystagmus

Jerk nystagmus

Fast/ slow oscillations due to vestibular, 8th nerve,

brainstem, cerebellum and connectors' lesions

Horizontal or rotary jerk nystagmus- due to

1. Central cause - nystagmus stays for long duration

2. Peripheral cause - associated with severe vertigo
Vertical jerk nystagmus - central lesion

Down beat jerk nystagmus - lesion around the foramen magnum such as mengioma, cerebellar
ectopia

Pendular nystagmus

Present vertically and in all directions of gaze

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Occulomotor nerve lesions
Signs:

1. unilateral complete ptosis

2. deviation of eye down and out

3. fixed and dilated pupil

Sparing of pupil indicates undamaged parasympathetics

Diabetic 3rd nerve infarction is usually painless

Trochlear nerve lesion

Complains of tortional diplopia (diplopia when looking
down)

Abducens nerve lesion

Cause horizontal diplopia

Esotropia (inward eye rotation) is seen

Could be damaged due to

1.MS

2. Infarction

3. Raised ICP (compressed against

petrous could be bilateral).

4. Infiltrated by tumours

Complete external ophthalmoplegia

 When 3rd, 4th , 5th cranial nerves are paralysed

 Can happen at orbital apex or cavernous sinus
 Wernickes encephalopathy could be a cause
 Other causes : myaesthenia gravis, botulism

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Facial nerve
Nucleus is at pons.

Innervates facial muscles, anterior 2/3 of tongue, stapedius of ear.

For upper face nerve fibers come from both cortices. For lower face it’s only from opposite cortex.

Unilateral facial nerve palsy.

Upper motor nerve lesion

 Only affects lower part of the face.

 Eye closure and wrinkling preserved.
 Slowness in teeth baring of the affected side occurs.

Lower motor nerve lesion.

 All facial muscles are gone. Dribbling, angle of mouth falling, corneal ulceration occurs.

Causes

UMNL=hemispheric stroke

LMNL=

1. at pons (also lateral rectus nerve palsy. Due to pontine tumours, ms, infarcts. When
PPRF and corticospinal tracts are also gone failure of conjugate lateral gaze palsy
toward the lesion and hemiparesis occurs )
2. at cp angle (due to cp angle tumors)
3. at petrous temporal bone in facial canal(2/3 anterior tongue sensation, hyperacusis
occurs.
4. due to bells palsy
5. Trauma
6. middle ear infection
7. ramsay hunt syndrome
8. at skull base (pagets disease). at parotid gland (tumors, sarcoidosis, trauma).

Bells palsy

 Due to viral infection or reactivation of herpes simplex (ramsay hunt).

 UL LMNL.
 Pain behind ear.

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 Diagnosis by clinically.
 If vesicles in palate or ear canal its Ramsay hunt.
 Involvement of other cranial nerves with facial weakness is not due to Bells palsy
 Lyme disease and HIV seroconversion are common causes
Mx,

85% recover over 4-12 weeks

Eye lubricants

Corticosterioids

Tarsorrhaphy

Rarely recurs

Ramsay hunt syndrome.

 Reactivation of herpes simplex in geniculate ganglion.

 Additionally deafness and vertigo seen
 Tx = acyclovir or valacyclovir with corticosteroids

BL causes for facial nerve palsy.

1. Infections (lyme, EBV, mastoiditis, diptheria, seroconversion of HIV)

2. Sarcoidosis
3. Pontine lesions
4. GBS
5. Myasthenia
6. Myotonic dystrophy

Hemifacial spasm

 Irregular painless unilateral spasm

 Starts at orbicularis oculi
 Usually due to compression of the root by the vascular structures
 If occurs with involvement of 5th cranial nerve (trigeminal neuralgia), condition is termed as tic
convulsions
 Treatment by botulinum injection with surgical decompression if necessary

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Strokes
Definitions
• Stroke: a syndrome of rapid onset neurological deficit caused by focal cerebral, spinal or retinal
infarction or haemorrhage.

• Transient ischaemic attack (TIA :) a brief episode of neurological dysfunction due to temporary
focal cerebral or retinal ischaemia without infarction. TIAs may herald a stroke.

E.g. A weak limb/aphasia/loss of vision, usually lasting seconds/ minutes with complete recovery.

Usually caused by micro emboli with infarction averted by cerebral autoregulation

Pathophysiology

Ischaemic stroke/infarction (85%): Pathological processes are arterial disease and atherosclerosis;
Common sites are arterial branch points

 Thrombotic (embolism or Vaso occlusion)

 Large-artery stenosis (embolic source)
 Small-vessel disease (vasculopathy caused by hypertension leading to “lacunar infarcts”)
 Cardio-embolic (in AF, Cardiac valve disease, Congenital heart diseases)
 Hypoperfusion (border-zone infarction in the watershed areas between vascular territories,
in severe hypotension. Parieto-Occipital Area between MCA and PCA territories is
particularly vulnerable)

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Haemorrhagic stroke (10%):

 Intracerebral hemorrhage
 Subarachnoid hemorrhage

Other (5%):

 Arterial dissection (<40s, Usually extra-cranial neck vessels, possible sequel to trauma,
associated with Marfan’s)
 Venous sinus thrombosis (1% of all strokes, pregnancy/ hypercoagulable states/
dehydration/ malignancy)
 Vasculitis

Risk Factors

Mainly are the risk factors for atherosclerosis

Others:

 Thrombocythaemia/ polycythaemia/ hyperviscosity states

 APLS (young stroke)
 Low-dose, Oestrogen-containing OCP in combination with background other risk factors (not
independently)
 Migraine
 Vasculitic syndromes
 Amyloidosis (recurrent cerebral haemorrhage)
 Hyperhomocysteinaemia (thrombotic strokes), not affected by folate therapy
 HIV, neurosyphilis, mitochondrial disease, Fabry’s disease
 Sympathomimetic drugs: Cocaine; Neuroleptics in older patients.
 CADASIL (cerebral dominant arteriopathy with subcortical infarcts and
leukoencephalopathy)

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Clinical syndromes

Transient ischaemic attack (TIA)

Anterior Circulation
strokes carry a poorer
prognosis

Common
All TIAs should be
REFERRED, SEEN,
INVESTIGATED and
MANAGED within 24 hours!

Amaurosis fugax is a sudden transient loss of vision in one eye (If an embolus occluding retinal
arteries seen via an ophthalmoscope during an attack- Hollenhorst plaque). A TIA causing amaurosis
fugax is often the first clinical evidence of internal carotid artery (ICA) stenosis – a warning sign of
incipient ICA territory stroke.

Diagnosis
Diagnosis based solely on its description. Consciousness is usually preserved. Source of
embolus and an underlying condition should be looked for.

Differential diagnosis
Mass Lesions

Focal epilepsy (Limb shaking TIA can occur and are pathognomonic of severe carotid stenosis causing
transient focal cerebral hypoperfusion)

Ix:
Doppler ultrasound of the internal carotid arteries

Cardiac echo

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ECG and 24-hour tape

MRI brain and MR or CT angiography

Treat with medical therapy and surgery if appropriate. Surgery or stenting of high-grade
symptomatic carotid stenosis within 1 week of TIA.

Cerebral infarction
Clinical picture is thus very variable, depending on the infarct site and extent.

Vaso-occlusion  Brain Ischaemia Infarction and Cell Death

(Electrical neuronal
failure symptoms seen
first)

Ischaemic penumbra:

 Infarcted region is surrounded by a swollen ischemic area that does not function but is
structurally intact.
 Can regain function after revascularization.
 Detected on MRI.

Clinical features
An acute onset (over minutes) of ‘negative’ symptoms indicating focal deficits in brain function, such
as weakness, sensory loss, dysphasia and visual loss, are the characteristic defining features of an
ischaemic stroke. The exact clinical picture depends on the vascular territory affected.

Anterior circulation infarcts

Includes infarcts in the territory of the internal carotid, middle cerebral (MCA), anterior cerebral
(ACA) and ophthalmic arteries.

Complete MCA occlusion: Contralateral hemiplegia and facial weakness, hemisensory loss and
neglect syndromes (parietal lobe – severe if the non-dominant side affected), eye deviation towards
the affected side, aphasia (dominant hemisphere lesions) and hemianopia.

Brain swelling of infarcted tissue leads to a high risk of death due to coning (malignant MCA
infarction). Decompressive craniectomy within the first 48 hours recommended.

Internal carotid occlusion: Similar to MCA occlusion, although collateral circulation may reduce the
infarct size.

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Lenticulostriate perforating arteries occlusion (or MCA occlusion with collateral circulation
protecting the cortex): Infarction of deep subcortical structures such as the internal capsule,
resulting in hemiplegia and hemisensory deficits.

ACA occlusion: Significantly less common than MCA infarcts, typically produce hemiparesis affecting
the leg more than arm, and frontal lobe deficits such as apathy or apraxia.

Posterior circulation infarcts

Brainstem infarction:

Cerebellar infarcts: Occur in isolation or as part of a more extensive brainstem syndrome. Swelling
of the cerebellum may cause brainstem compression and coma or obstructive hydrocephalus
necessitating decompressive surgery.

Basilar artery thrombosis: more common than embolism. The clinical picture depends on the level
of the occlusion and the branch vessels affected. (Coma, Locked-in syndrome/ top of the basilar
syndrome etc.)

Posterior cerebral artery infarcts: Typically embolic. Homonymous hemianopia if unilateral lesion,
and cortical blindness (Anton’s syndrome) if bilateral lesions.

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Ix:
Aims to:
 Confirm the clinical diagnosis,
distinguish between haemorrhage and
thromboembolic infarction, and
exclude stroke mimics

 Identify an underlying cause for the

purposes of secondary prevention and
identification of stroke mimics.

CT will exclude haemorrhage, but

only show subtle features of
infarction in early stages. Therefore
repeat at 24-48 hrs!

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 Mx:

Antiplatelet therapy and anticoagulation- High-dose aspirin (300mg) is started 24hours after thrombolysis,
continued for 2 weeks before switching to clopidogre. Anticoagulants are started for atrial fibrillation-associated
cardio-embolic stroke usually after 2 weeks to reduce the risk of acute haemorrhagic transformation of infarcts

Decompressive craniectomy- Performed within 48hours in MCA strokes causing infarction of more than 50% of
the MCA territory to prevent coning and improve long-term outcome
Stroke units- Direct admission to a stroke unit has been demonstrated to be one of the most effective 22
interventions in acute stroke
Secondary prevention interventions
Antihypertensive therapy
 Recognize and control high blood pressure (for both primary and secondary stroke
prevention)
 Transient hypertension, often seen following stroke, usually does not require treatment,
unless DBP>100mmHg
 Sustained severe hypertension needs treatment after 72 hours (lowered slowly to avoid any
sudden fall in perfusion)

Lipid-lowering therapy

 Statins (atorvastatin 40 mg) should be offered to all patients unless there is a

contraindicated, (Target total cholesterol <4 mmol/L, LDL<2 mmol/L).

Lifestyle modification and education

 Education of patient
 Smoking cessation
 Advice about diet, exercise, weight reduction and alcohol consumption (Started at stroke
unit)

Surgery and stenting for carotid stenosis

 A second imaging modality, such as CT angiography, should be performed to confirm the
results of Doppler studies
 Carotid endarterectomy should be performed within 2 weeks in patients with 70–99%
stenosis on the affected side (if initial stroke was not severely disabling)
 Screening asymptomatic individuals for carotid stenosis is not helpful. Carotid occlusion is
always treated conservatively (there is no risk of distal embolization).

Stroke in the elderly

 Thrombolysis is not contraindicated, Benefit from good rehabilitation

 Carotid endarterectomy over 75 years of age is riskier than for younger patients

Rehabilitation: MDT Approach

 Physiotherapy (especially in the first few weeks): relieve spasticity, prevent contractures and
teach patients to use walking aids
 Baclofen and/or Botox sometimes helpful for severe spasticity.
 Speech and language therapists are vital: return of speech is hastenedby conversation
 Swallowing: if unsafe due to aspiration risk, either NG feeds or Percutaneous Gastrostomy
 Psychologists: Loss of self-esteem makes depression common.
 At home, aids and alterations may be needed

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Prognosis
 25% of patients die within 2 years of a stroke (10% within first month)
 Recurrent strokes are common (10% in the first year)
 Gradual improvement usually follows stroke, with a plateau in recovery after 12 months

INTRACRANIAL HAEMORRHAGE

Intracerebral haemorrhage
Aetiology
Hypertension:
 Rupture of microaneurysms (Charcot–Bouchard aneurysms) and degeneration of small,
deep, penetrating arteries are the principal pathologies.
 Usually massive, often fatal, and occurs in chronic hypertension
 Sites: basal ganglia, pons, cerebellum and subcortical white

Cerebral amyloid angiopathy (CAA):

 Deposition of amyloid-β in the walls of small and medium-sized arteries in normotensive
patients
 Causes lobar intracerebral haemorrhage (especially posterior, i.e. occipital/parietal lobes),
 Often recurrent
 More common in patients with Alzheimer’s disease

Secondary:
 Arteriovenous malformations, cavernomas, aneurysms, dural venous thrombosis
 Coagulopathies, anticoagulants and thrombolysis may cause haemorrhage

Clinical features and investigations

 Intracerebral haemorrhage is more often associated with severe headache or coma.
 Patients on oral anticoagulants should be assumed to have had a haemorrhage unless it is
proved otherwise.
 Brain haemorrhage is seen on CT imaging (intraparenchymal, intraventricular or
 Subarachnoid)
 Routine MRI may not identify an acute small haemorrhage reliably in the first few hours but
MRI and MR angiography are necessary to identify underlying vascular malformations

Management of haemorrhagic stroke

Medical

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  Treatment should be on a stroke unit or NICU
 Frequent monitoring of GCS and neurological signs is essential
 Antiplatelet drugs are contraindicated. Anticoagulation should be rapidly reversed where
possible (warfarin- IV Vit K and clotting factor concentrates)
 Control of hypertension with IV drugs if SBP>180mmHg
 Measures to reduce ICP may be required: mechanical ventilation and mannitol

Surgical

 Cerebellar haematomas may cause obstructive hydrocephalus/ coma due to brainstem

compression; urgent neurosurgical clot evacuation is lifesaving (and is required where the
haematoma is >3 cm or the patient is drowsy or deteriorating)
 Liaison with neurosurgeons is vital for non-Cerebellar bleeds
 Placement of an external ventricular drain is needed if obstructive hydrocephalus develops
.

Subarachnoid haemorrhage
Aetiology

Clinical features of subarachnoid haemorrhage

 Sudden, very severe headache, often occipital (mean time to peak headache 3 min):
Thunderclap Headache
 Headache is usually followed by vomiting and often by coma and death
 Survivors of SAH may remain comatose or drowsy for hours, days or longer
 Following major SAH, there is neck stiffness and a positive Kernig’s sign
 Papilloedema is sometimes present, with retinal and/ or subhyaloid haemorrhage

Investigations
 CT imaging is the immediate investigation

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  Detect subarachnoid blood is 95% within 24 hours of onset but much lower over subsequent
days)
 Lumbar puncture is not necessary if SAH is confirmed by CT, but should be performed if
doubt remains. CSF becomes yellow (xanthochromic) within 12 hours of SAH and remains
detectable for 2 weeks
 Spectrophotometry to estimate bilirubin in the CSF released from lysed cells is used to
define SAH with certainty
 CT angiography or catheter angiography to identify the aneurysm or other source of
bleeding is performed in patients potentially fit for surgery

Differential diagnosis
For sudden, severe headache: Migraine, Acute bacterial meningitis, cervical artery dissection

Complications
 Obstructive hydrocephalus,
 Arterial spasm (also a poor prognostic feature)

Management
 Bed rest and supportive care
 Hypertension controlled: Nimodipine for 3 weeks, reduces mortality
 All SAH cases should be discussed urgently with a neurosurgical centre
 Where angiography demonstrates an aneurysm, endovascular to promote thrombosis and
ablation of the aneurysm, is the first-linetreatment

Subdural and extradural bleeding

Subdural haematoma
 Following rupture of a vein usually follows a head injury, sometimes a trivial one
 Chronic, apparently spontaneous, SDH is common in the elderly, and also occurs with
anticoagulants
 Headache, drowsiness and confusion common

Extradural haemorrhage
 Extradural haemorrhage (EDH) typically follows a linear skull vault fracture tearing a branch
of the middle meningeal artery; blood accumulates rapidly over minutes or hours
 Lucid interval is characteristic

Mx:

 Immediate imaging. CT is first line as it is more available, MRI is more sensitive for the
detection of small haematomas
 EDHs require urgent neurosurgery
 When the patient is far from a neurosurgeon, such as in wartime or at sea, drainage through
skull burr holes has been lifesaving when an EDH has been diagnosed clinically

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  Subdural bleeding usually needs less immediate attention but close neurosurgical liaison is
necessary. Even large collections can resolve spontaneously without drainage. Serial imaging
is required to assess progress

Cortical venous thrombosis and dural venous sinus thrombosis

 Associated with a prothrombotic risk factor
 Head injury is also a cause

Cortical venous thrombosis

The venous infarct leads to headache, focal signs (e.g. hemiparesis) and/or seizures. Cortical
haemorrhagic infarction is shown on MRI.

Dural venous sinus thromboses

Cavernous sinus thrombosis causes eye pain, fever, proptosis and chemosis. External and internal
ophthalmoplegia with papilloedema develops.

Management
 MRI and MR venography (MRV) to show occluded sinuses and/or veins
 Heparin initially, followed by warfarin or other oral anticoagulants for 6 months
 Anticonvulsants are given if necessary.

Spinal cord disease

Cord extends from junction between the C1 and the medulla, to the lower vertebral body of L1, end
as conus medullaris.

Blood supply- Anterior spinal artery and a plexus on the posterior cord.

1. Spinal cord compression

Clinical features of chronic and subacute cord compression - Spastic paraparesis or tetraparesis,
radicular pain at the level of compression, and sensory loss below the compression (sensory level is
usually 2–3 dermatome levels below the level of anatomical compression).

Causes of spinal cord compression

1. Spinal cord tumours

a. Extramedullary
b. Intramedullary (less common and typically progress slowly, sometimes over many years)
2. Vertebral body destruction by bone metastases, e.g. prostate / breast primary cancer, is a
common cause of spinal cord compression

27
 3. Disc and vertebral lesions
a. Chronic degenerative and acute central disc prolapse-chronic compression due to cervical
spondylotic myelopathy, most common cause of a spastic paraparesis in an elderly person
b. Trauma
4. Inflammatory
a. Epidural abscess
b. Tuberculosis (Pott’s paraplegia)
c. Granulomatous
5. Epidural haemorrhage/haematoma – Due to anticoagulant therapy, bleeding disorders or
trauma, and can follow LP when clotting is abnormal.

Spinal cord neoplasms

Extradural

Metastases: Bronchus, Breast, Prostate, Lymphoma, Thyroid, Melanoma

Extramedullary Intramedullary

• Meningioma • Glioma
• Neurofibroma • Ependymoma
• Ependymoma • Haemangioblastoma
• Lipoma
• Teratoma

Management:

Acute spinal cord compression is a medical emergency- MRI is the imaging technique of choice, if
decompression is not performed promptly, irreversible cord damage ensues.

2. Transverse myelitis
 Acute inflammatory disorder of the spinal cord  swelling and loss of function.
 One or two spinal segments are affected.
 Clinically, a myelopathy evolves over days, and recovery (often partial) follows over weeks or
month
 Ix- MRI with gadolinium enhancement of spine is sensitive.

Brain images to look for evidence of demyelination.

CSF may be inflammatory with an excess of lymphocytes.

Causes:

1. Para-infectious autoimmune inflammatory response- most common cause and may follow viral
infection or immunization.
2. Systemic inflammatory disorders, e.g., SLE, Sjögren’s, sarcoidosis.
3. Infection- viruses –herpesviruses; mycobacteria, e.g. tuberculosis; bacteria – e.g. syphilis and
Lyme disease; or flatworms – e.g. schistosomiasis.

28
 4. Multiple sclerosis
5. Neuromyelitis optica

Treatment - High-dose steroids or other immunosuppression, or antimicrobial therapy in the case of

specific infections.

3. Anterior spinal artery occlusion

Infarction of the anterior two-thirds of the spinal cord acute paraplegia and loss of pain and
temperature sensation.

Causes- Aortic atherosclerosis, dissection, trauma or cross-clamping in surgery, vasculitis, emboli,

haematological disorders causing thrombosis and severe hypotension.

Other spinal cord disorders

4. Arteriovenous malformations of the cord.

5. Genetic disorders – hereditary spastic paraparesis (HSP)

6. Vitamin B12 deficiency- Subacute combined degeneration of the cord.

7. Syringomyelia
 Syringomyelia- fluid-filled cavity within the spinal cord.
 Congenital- associated with the Arnold–Chiari malformation.
 Acquired-spinal cord trauma, intrinsic cord infection.
 Damage to lateral spinothalamic tract- loss of pain and temperature with intact JPS (dissociative
sensory loss).
 Damage to anterior horn cells –LMN type lesion in upper limp.
 Damage to lateral corticospinal tract -UMN type lesion usually in lower limp.
 Brainstem signs – as the syrinx extends into the brainstem (syringobulbia) (eg:Tongue atrophy
and fasciculation, bulbarpalsy, a Horner’s syndrome and impairment of facial sensation).

Motor neurone disease

 Causing progressive weakness and eventually death (due to respiratory failure or aspiration).
 Relatively uncommon.
 Present -50-70 years, <70 years men are affected more than women.
 Affects UMN and LMN in the spinal cord, cranial nerve motor nuclei and cortex. Sensory system
is not involved.
 Aetiology Familial

Sporadic (no established risk factor)

29
 Clinical features

Four main clinical patterns are seen.

Amyotrophic lateral Progressive muscular Progressive bulbar Primary lateral sclerosis

sclerosis atrophy and pseudobulbar
Least common
palsy
Classic paraneoplastic Pure LMN presentation.
Confined to UMN
presentation with Lower cranial nerve
Starting in one limb and
simultaneous nuclei and their Slowly progressive tetra
gradually spreading to
involvement of UMN supranuclear paresis and
involve other adjacent
and LMN, usually in one connections are pseudobulbar palsy.
spinal segments.
limb, spreading initially involved.
gradually to other limbs
Dysarthria, dysphagia,
and trunk muscles.
nasal regurgitation of
Brisk reflex in a wasted fluids and choking are
muscle - classic sign the presenting
symptoms.

Pseudobulbar palsy-
Emotional
incontinence

 Diagnosis is largely clinical.

 Denervation of muscles is confirmed by EMG.
 Cervical myeloradiculopathy and multifocal motor neuropathy appear like MND.

Prognosis:

 Survival > 3 years- unusual.

 Rare MND - survive for a decade or longer.
 No treatment has been shown to influence outcome.
 Riluzole, a sodium-channel blocker that inhibits glutamate release, slows progression slightly.
 Supportive mx- Non-invasive ventilatory support and feeding via a gastrostomy.

Cauda equina syndrome

 Due to central lumbosacral disc protrusion. Multiple lumbosacral nerve roots are involved.
 Clinical features -Bilateral flaccid lower limb weakness, sacral numbness, retention of urine,
erectile dysfunction and areflexia, usually with back pain.
 Onset is acute (acute flaccid paraparesis) or chronic (intermittent claudication).

Poliomyelitis
 Caused by Poliovirus which is an Enterovirus species and spread via the faecal–oral route.
 Propensity for the nervous system, especially the anterior horn cells of the spinal cord and
cranial motor neurons.

30
Clinical features:

 Incubation period is 7–14 days.

 Asymptomatic seroconversion -most common.
 Paralytic poliomyelitis (Acute flaccid paralysis)-
 Rare presentation, follows initial illness of fever, sore throat and myalgia. Causing asymmetric
flaccid paralysis without sensory involvement.
 Predisposing factors for AFP - male sex, exercise early in the illness, trauma, surgery or
intramuscular injection, and recent tonsillectomy (bulbar poliomyelitis).
 Late complications of poliomyelitis -Aspiration pneumonia, myocarditis, paralytic ileus and
urinary calculi.
 AFP- now more commonly caused by other Enteroviruses than by polioviruses.

Diagnosis - by detection of Enterovirus RNA in a throat swab, faecal sample or CSF.

Management – supportive, respiratory support with IPPV is required if the muscles of respiration
are involved.

Nervous System Infection

Meningitis
Microorganisms reach the meninges either by direct extension from the ears, nasopharynx, cranial
injury or congenital meningeal defect, or by bloodstream spread. Non-infective causes of meningeal
inflammation include malignant meningitis, intrathecal drugs and blood following subarachnoid
haemorrhage.

Infective causes of meningitis in the UK

Bacteria

 Neisseria meningitidis
 Streptococcus pneumoniaea
 Staphylococcus aureus
 Streptococcus group B
 Listeria monocytogenes
 Gram-negative bacilli, e.g. Escherichia coli
 Mycobacterium tuberculosis
 Treponema pallidum

Viruses

 Enteroviruses
o ECHO
o Coxsackie
 (Poliomyelitis – mainly eradicated worldwide)
 Mumps
 Herpes simplex

31
  HIV
 Epstein–Barr

Fungi

 Cryptococcus neoformans
 Candida albicans
 Coccidioides immitis, Histoplasma capsulatum, Blastomyces dermatitidis (USA)

Clinical features

The meningitic syndrome

Simple triad: headache, neck stiffness and fever. Photophobia and vomiting are often present.

Clinical clues in meningitis

Clinical feature Possible cause

Petechial rash Meningococcal infection

Skull fracture
Ear disease
Congenital CNS lesion Pneumococcal infection

HIV with
Immunocompromised patients opportunistic infection

Rash or pleuritic pain Enterovirus infection

International travel Malaria

Occupational (work in drains, canals, polluted water, recreational

swimming)
Clinical: myalgia, conjunctivitis, jaundice Leptospirosis

Mx:

Immediate treatment for suspected meningococcal meningitis at first contact before investigation

 Third-generation cephalosporin, e.g. cefotaxime, as empirical therapy (increasing rates of

penicillin resistance)
 Switch to benzylpenicillin if sensitivity confirmed
 Dexamethasone 0.6 mg/kg i.v. with or before first dose of antibiotic

32
Viral meningitis

No serious sequelae. Benign

Chronic meningitis

Intracranial mass lesion, with headache, epilepsy and focal signs. Cerebral malaria can mimic
bacterial meningitis.

Tuberculous meningitis (TBM)

Syphilis, sarcoidosis and Behçet’s also cause chronic meningitis.

Differential diagnosis

Sudden headache of subarachnoid haemorrhage, migraine and acute meningitis. Meningitis should
be considered seriously in anyone with headache and fever, and in any sudden headache. Neck
stiffness should be looked for; it may not be obvious.

Ix

Normal Viral Pyogenic Tuberculous

Appearance Crystal clear Clear/turbid Turbid/purulent Turbid/viscous

Mononuclear
cells <5/mm3 10–100/mm3 <50/mm3 100–300/mm3

Polymorph
cells Nil Nila 200–300/mm3 0–200/mm3

Protein 0.2–0.4 g/L 0.4–0.8 g/L 0.5–2.0 g/L 0.5–3.0 g/L

blood > blood < blood < blood

Glucose glucose glucose glucose glucose

33
Antibiotics in acute bacterial meningitis

Alternative (e.g.
Organism Antibiotic allergy)

Third-generation cephalosporin, e.g.

cefotaxime (+ vancomycin in areas of high
pneumococcal penicillin/cephalosporin Benzylpenicillin and
Unknown pyogenic resistance) chloramphenicol

Age >50 or Co-trimoxazole

Immunocompromised As above but add ampicillin to cover Listeria for Listeria

Third-generation cephalosporin initially

Meningococcus Switch to benzylpenicillin if confirmed sensitive Cefotaxime

Third-generation cephalosporin, e.g.

Pneumococcus cefotaxime Penicillin

Third-generation cephalosporin, e.g.

Haemophilus cefotaxime Chloramphenicol

High-dose steroid (dexamethasone 0.6 mg/kg i.v. for 4 days), given with or before the first dose of
antibiotics, has been shown to reduce neurological complications in bacterial meningitis (e.g.
deafness

Prophylaxis

Meningococcal infection

 Chemoprophylaxis with rifampicin or ciprofloxacin should be offered to all close contacts.

MenC vaccine is given in the UK and MenB, a meningococcal B vaccine, is now available for
population immunization of infants and for use in outbreaks.
 Pneumococcal immunization - for immune-compromised

Tuberculous meningitis

Treatment with antituberculosis drugs (see p. 1111) – rifampicin, isoniazid and pyrazinamide – must
commence on a presumptive basis.

And continue for at least 9 months. Ethambutol should be avoided because of its eye complications.
Adjuvant corticosteroids, such as prednisolone 60 mg for 3 weeks.

Cells in a sterile CSF (pleocytosis)

 A raised CSF cell count is present without an evident infecting organism

 Partially treated bacterial meningitis

34
  Viral meningitis
 Tuberculous or fungal meningitis
 Intracranial abscess
 Neoplastic meningitis
 Parameningeal foci, e.g. paranasal sinus
 Syphilis
 Cerebral venous thrombosis
 Cerebral malaria
 Cerebral infarction
 Following subarachnoid haemorrhage
 Encephalitis, including HIV
 Rarities, e.g. cerebral malaria, sarcoidosis, Behçet syndrome, Lyme disease, endocarditis,
cerebral vasculitis

Encephalitis
Herpes simplex (HSV), varicella zoster (VZV) and other herpes group viruses, HHV-6, 7, enteroviruses
and adenovirus.

Investigations

 MRI shows areas of inflammation and swelling, generally in the temporal lobes in HSV
encephalitis. Raised intracranial pressure and midline shift may occur, leading to coning.
 EEG shows periodic sharp and slow-wave complexes.
 CSF shows an elevated lymphocyte count (95%).
 Viral detection by CSF PCR is highly sensitive for several viruses, such as HSV and VZV.
However, a false-negative result may occur within the first 48 hours of symptom onset.
Serology (blood and CSF) is also helpful.
 Brain biopsy is rarely required since the advent of MRI and PCR.

Management

Immediately with intravenous acyclovir (10 mg/kg 3 times a day for 14–21 days

Autoimmune encephalitis

Paraneoplastic limbic encephalitis (PLE). PLE is seen particularly with small-cell lung cancer and
testicular tumours.

CNS and peripheral nerve disease in HIV

HIV seroconversion can cause meningitis, encephalitis, Guillain–Barré syndrome and Bell’s palsy

Herpes zoster (shingles)

35
Neurosyphilis

Meningovascular syphilis

This causes:

 subacute meningitis with cranial nerve palsies and papilloedema

 a gumma – a chronic expanding intracranial mass
 paraparesis – a spinal meningovasculitis

Management

Benzylpenicillin 1 g daily i.m. for 10 days in primary infection eliminates any risk of neurosyphilis.

Neurocysticercosis

Pork tapeworm, Taenia solium, Epilepsy is the most common clinical manifestation

Mx-control of seizures, and the anthelminthic agent, albendazole.

Subacute sclerosing panencephalitis

Persistence of measles antigen in the CNS.

Diagnosis is made by high measles antibody titre in blood and CSF. Measles immunization protects
against subacute sclerosing panencephalitis (SSPE).

Brain abscess
Typical bacteria found are Streptococcus anginosus and Bacteroides species.

Urgent imaging is essential. MRI shows a ring-enhancing massLP is dangerous and should not be
performed.

Neurosurgical aspiration with stereotactic guidance allows the infective organism to be identified.
Treatment is with high-dose antibiotics and, sometimes, surgical resection/decompression.

Muscle disease

 Acquired
o Inflammatory
o Polymyositis
o Dermatomyositis
o Inclusion body myositis
o Viral, bacterial and parasitic infection
o Sarcoidosis

36
  Endocrine and toxic
o Corticosteroids/Cushing’s
o Thyroid disease
o Calcium disorders
o Alcohol misuse
o Drugs, e.g. statins

 Myasthenic
o Myasthenia gravis
o Lambert–Eaton myasthenic–myopathic syndrome (LEMS)

 Genetic dystrophies
o Duchenne
o Facioscapulohumeral
o Limb girdle and others

 Myotonic
o Myotonic dystrophy
o Myotonia congenita

 Channelopathies
o Hypokalaemic periodic paralysis
o Hyperkalaemic periodic paralysis

 Metabolic
o Myophosphorylase deficiency (McArdle syndrome)
o Other defects of glycogen and fatty acid metabolism

 Mitochondrial disease
 Drugs
o Drug-induced muscle disorders include proximal myopathy
(steroids), muscle weakness (lithium), painful muscles (fibrates), rhabdomyolysis (a
fibrate combined with a statin, or interaction between statins and other drugs such
as certain antibiotics) and malignant hyperpyrexia. Most respond to drug
withdrawal.

Neuromuscular junction disorders

Myasthenia gravis
Characterized by weakness and fatiguability of proximal limb, bulbar and ocular muscles Immune
complexes of anti-AChR IgG and complement are deposited at the postsynaptic membranes, causing
destruction of AChRs. Thymic hyperplasia is found in 70%. 10%, a thymic tumour.

37
Clinical features

Weakness and fatiguability are typical. Limb muscles (proximal), extraocular muscles, speech, facial
expression and mastication muscles are commonly affected.

Investigations

Serum anti-AChR and anti-MuSK antibodies.

Repetitive nerve stimulation and single-fibre EMG.

Tensilon (edrophonium) test

Drug treatment

Pyridostigmine

prolongs acetylcholine action by inhibiting cholinesterase.

Muscarinic side-effects, such as colic and diarrhoea, are common; oral atropine (antimuscarinic)
0.5 mg helps to reduce this.

Thymectomy improves myasthenia in patients with thymic hyperplasia and positive AChR antibodies.

Plasmapheresis and intravenous immunoglobulin

These produce a rapid dramatic response and are used in exacerbation

Lambert–Eaton myasthenic–myopathic syndrome

Is a paraneoplastic manifestation of small-cell bronchial carcinoma due to defective acetylcholine
release at the neuromuscular junction.

Duschene and Beckers muscular dystrophy

Inherited as X-linked recessive.

Duchenne muscular dystrophy (DMD) occurs in 1 in 3000 male infants.

There is absence of the gene product dystrophin.

In Becker’s dystrophy, dystrophin is present but levels are low.

Becker’s muscular dystrophy is less severe than Duchenne and weakness only becomes apparent in
young adults.

Clinical features

- DMD has Gowers sign

- There is initially a proximal limb weakness with calf pseudohypertrophy. The myocardium is
affected.

38
 - Diagnosis is often suspected clinically.
- Biopsy shows variation in muscle fibre size, necrosis, regeneration and replacement by fat.

Management

- Steroids
- Physiotherapy
- Multidisciplinary care

Movement disorders
• Two types
1. Slowed movements - hypokinesias (Parkinsonism)
2. Excessive involuntary movements - hyperkinesias
• Both types can coexist
• Many of these (not all) relate to dysfunction of basal ganglia

Parkinsonian disorders (≠ Parkinson’s disease)

Idiopathic Parkinson’s disease (= Parkinson’s disease)

• Prevalence increases sharply with age

• Small increased risk with rural living and drinking well water
• Studies show that non-smokers have a higher risk than smokers
• Usually not familial
• But early onset PD has significant genetic component
• Responsible genes are called PARK 1-11
• Pathological hallmarks of PD
- Neuronal inclusions Lewy bodies
- Loss of dopaminergic neurons from pars compacta of substantia nigra
• Lewy bodies contain α-synuclein and ubiquitin
• These changes become widespread as disease progresses

Clinical features of PD

• Almost always present with typical motor symptoms of tremor and slowness of movement
• Usually pathological process starts many years before this

• Prodromal pre-motor symptoms

• non specific symptoms that occur before motor symptoms
• anosmia (90%)
• depression/ anxiety (50%)
• aches and pains
• sleep disorders
• restless leg syndrome
• constipation, urinary urgency, hypotension

39
• Motor symptoms
• akinesia (bradykinesia) - slowing of movement, difficulty initiating movement
• upper limb usually affected first and almost always unilateral for first few years
• tremor - presenting symptom in 70%, pill-rolling tremor
• starts in fingers or hand unilaterally then spreading to the leg on the same side, then after years
to the opposite side
• tremor present at rest, reduces or stops with movement
• rigidity (actually a sign!) lead pipe and cogwheel rigidity
• postural and gait disturbances - can lead to falls but a late feature, if present during first 5 years
suspect an alternative diagnosis
• apart from above core features micrographia (small writing), mask like appearance, reduced
blinking leads to serpentine stare

• Speech becomes quiet, swallowing difficulty is a late feature

• Cognitive and psychiatric changes - dementia, depression, visual hallucinations, psychosis,
cognitive impairment

Clinical evolution of PD

• Most respond well to treatment

• Initially symptoms are well controlled for several years
• In the late stage treatment-unresponsive features emerge - swallowing difficulty, cognitive
impairment, loss of postural stability and falls

Management of PD

• Education
• Encourage physical activity
• Dopamine replacement for motor symptoms - levodopa or dopamine agonist
• Treatment of non motor symptoms
• Levodopa is the most effective form of treatment
• Can be combined with dopa decarboxylase inhibitor - carbidopa, benserazide
• Other drugs - Selegiline, Amantadine
• Other treatment methods - deep brain stimulation, levodopa intestinal gel infusion tissue
transplantation
• Motor complications of dopamine replacement therapy
- wearing off - duration of effect of levodopa becomes progressively shorter
- dyskinesias - involuntary movements
- on/off phenomena - transitions from mobile to immobile

Other akinetic-rigid syndromes

• Drug induced parkinsonism - antipsychotics

• Atypical parkinsonism - progressive supra-nuclear palsy, multiple system atrophy, cortico-basal
degeneration
• Red flag symptoms symptoms suggesting atypical parkinsonism
• symmetrical presentation
• absence of tremor
• early falls
• levodopa unresponsiveness

40
 • additional neurological features
• Wilson’s disease - copper deposition in basal ganglia, cornea and liver
• Always suspect if movement disorder + cirrhosis in young patients

Hyperkinetic movement disorders

• tremor - essential tremor, often inherited

• chorea - wide variety of causes
- thyrotoxicosis
- SLE
- Huntington’s disease
- Sydenham’s chorea (post-infectious)
• myoclonus
• tics - stereotyped movements like blinking, sniffing, grimacing Tourette’s syndrome is a common
cause.
• dystonia - several types such as primary, secondary, hereditary degenerative and paroxysmal. All
focal dystonias treated with botulinum toxin.

Neuropathies
Mechanisms of damage to peripheral nerves
• Demyelination - damage to Schwann cells, e.g. Guillain-Barré syndrome
• Axonal degeneration - toxic and metabolic neuropathies
• Compression - carpal tunnel syndrome
• Infarction - microinfarction of vasa navorum in diabetes and arteritis
• Infiltration - by inflammatory cells, e.g. leprosy

Types of peripheral nerve disease

• Neuropathy
• Mononeuropathy - affecting only a single nerve
• Mononeuritis multiplex - several individual nerves affected
• Polyneuropathy - diffuse, symmetrical peripheral disease
- can be motor, sensory, sensorimotor, autonomic
- classified as demyelinating and axonal types
• Radiculopathy - nerve roots affected

Mononeuropathies

Peripheral nerve compression and entrapment

• Most common ones are carpal tunnel syndrome, ulnar nerve compression, radial nerve
compression, common peroneal nerve palsy
• Diagnosis confirmed by nerve conduction studies
• Causes for CTS
- hypothyroidism
- pregnancy (third trimester)
- rheumatoid disease

41
 - acromegaly
- amyloidosis

Mononeuritis multiplex
• Occurs in
- DM
- leprosy
- vasculitis
- malignancy
- neurofibromatosis
- HIV and hepatitis C

Polyneuropathies

Guillain-Barré syndrome
• Also called acute inflammatory demyelinating polyradiculoneuropathy (AIDP)
• Most common acute polyneuropathy
• Usually demyelinating, occasionally axonal
• Post-infectious, immune mediated, often 1-3 weeks after a viral infection
• Campylobacter jejuni and cytomegalovirus infections are well-recognized causes
• Clinical features
- weakness of distal limb muscles
- distal numbness may be there, but no sensory level
- weakness progress proximally (upwards)
- loss of tendon reflexes
- respiratory muscle paralysis and autonomic dysfunction can be fatal
- Miller-Fisher syndrome - a rare proximal variant causing ocular muscle palsies and ataxia
• Diagnosis on clinical grounds and confirmed by nerve conduction studies - reduced velocity
• Can diagnose retrospectively by doing a LP, increased protein with normal cell count
(cytoprotein dissociation)
• In Miller-Fisher syndrome anti-GQ1b antibodies (90% sensitivity)

Management of GBS
• DVT prophylaxis
• Monitoring for respiratory muscle and autonomic involvement
• Ventilatory support if rapid progression
• IV immunoglobulin (IV Ig)
• Plasma exchange
• Both has similar efficacy
• No place of corticosteroids

Chronic inflammatory demyelinating polyradiculoneuropathy

• Develops over months
• Distal limb weakness with sensory loss, sometimes cranial nerve involvement
• Responds to long term immunosuppression - IV Ig or steroids

42
Metabolic neuropathies
• DM is the commonest cause of neuropathy in developed countries
- distal symmetrical sensory neuropathy
- acute painful sensory neuropathy
- mononeuropathy and mononeuritis multiplex
- diabetic amyotrophy
- autonomic neuropathy
• Other causes - uraemia, thyroid disease, porphyria, amyloidosis

Toxic neuropathies
• Alcohol - in chronic use
• Others - lead, acrylamide, arsenic

Vitamin deficiency neuropathies

• Thiamine - beriberi, also causes Wernicke’s encephalopathy and Korsakoff syndrome
• Pyridoxine - mainly sensory, occurs during anti TB treatment with isoniazid
• Vitamin B12 - peripheral nerves, also affects spinal cord

Hereditary neuropathies
• Charcot–Marie–Tooth disease - AD inheritance

Paraproteinaemic neuropathies
• In up to 70% with a serum paraprotein
• Most are associated with MGUS
• IgM paraproteins - usually demyelinating
• POEMS syndrome

Headache

Pain arising from

Intracranial structures extracranial structures

Meninges, dural venous sinuses, Extracranial vessels, scalp, neck and

blood vessels facial muscles, paranasal sinuses, eyes
and teeth

• Mediated by the V th and IX th cranial nerves and upper cervical sensory roots.
• Most headaches will be benign.

43
 PRIMARY SECONDARY

 Migraine  Raised intracranial

 Trigeminal autonomic pressure (idiopathic
cephalgias intracranial hypertension)
 Tension type headache  Infections (meningitis,
 Chronic daily headache sinusitis)
 1ry stabbing headache  Giant cell arteritis
 1ry Cough headache
 Intracranial haemorrhage,
 1ry Sex headache
esp. subarachnoid
 Others-hemicrania continua,
haemorrhage or subdural
primary exertional headache,
haematoma
hypnic headache and primary
thunderclap headache.
 Low cerebrospinal fluid
volume (low-pressure)
headache
 Post-traumatic headache
 Cervicogenic headache
 Acute glaucoma

Primary headache disorders

1. Migraine
• Most common cause of episodic headache.
• Women > men.
• Onset - before 40 years.
• Associated with sensory sensitivity - to light, sound or movement, and sometimes with nausea
and vomiting.
• Spectrum of severity between individuals and from one attack to another.
• Inability to function normally during episodes.
• May transform into chronic daily headache.

Simplified diagnostic criteria

Headache lasting 4 hours to 3 days (untreated)

At least two of:

• Unilateral pain (may become holocranial later in attack)

• Throbbing-type pain
• Moderate to severe intensity
• Motion sensitivity (headache made worse with head movement or physical activity)

At least one of:

• Nausea/vomiting
• Photophobia/phonophobia
• Normal examination and no other cause of headache

(Presence of aura not required for diagnosis)

44
 Migraine without aura Migraine with aura

• Starts around puberty • Experience focal neurological

• Reduced with sleep, prefer to in dark, quite symptoms immediately
environment preceding the headache phase
• Allodynia in some or all attacks.
• Trigger factors, • Aura- evolves over 5–20
o Sleep (too little or too much) minutes. Rarely lasts longer
o Stress than 60 minutes.
o Hormonal changes–changes in oestrogen • Visual aura - common type, with
levels positive symptoms shimmering,
o Eating –skipping meals and alcohol teichopsia (zigzag line).
o Sensory stimuli- bright lights or loud sound • Positive sensory symptoms
o Physical exertion, changes in weather (mainly tingling), dysphasia.
patterns • Rarely, loss of motor function.
o Minor head injuries

Acephalic migrainous aura frequently misdiagnosed as a TIA.

Migraine TIA

Evolution of symptoms over minutes and Acute onset and negative symptoms
the presence of positive symptoms in
(Visual loss)
aura

(Visual distortion and teichopsia)

Basilar migraine- associated with brainstem aura- perioral paraesthesiae, diplopia, unsteadiness and
rarely, reduced level of consciousness.

Hemiplegic migraine - rare autosomal dominant disorder causes a hemiparesis and/or coma and
headache, with recovery within 24 hours. Some have permanent cerebellar signs.

Management

General measures include:

• Explanation

• Avoidance of trigger factors and lifestyle modification

45
Pharmacological

Treatments of Acute attack Suppression medication (preventive TX)

Nonspecific specific  When migraine episodes are frequent

>1–2 per month, and impacting on quality of life
1.Simple analgesic 1.Triptans
 Period of 3–6 months treatment is
 Paracetamol (5-HT1B/1D agonists) sufficient to reduce headache frequency and
 NSAIDs(naproxen) severity.
Sumatriptonszolmitriptan  Not be effective where ongoing
 High dose
dispersible asprin analgesic overuse is an issue.

2.Antiemetics Avoided when there is 1.Anticonvulsants- Valproate or topiramate

 Metochlopramide
 Domperidone
As soon as possible after
the episode
Frequent repeated use -
analgesic associated
chronic daily headache
vascular disease, they should
not be overused.
2. CGRP antagonists
Telcagepant
2. Beta-blockers-propranolol slow-release
3. Tricyclics- amitriptyline
4. Candesarta
5.Antidepressants- venlafaxine
6.Botulinum toxin- treatment for chronic
migrain

7. Pizotifen- rarely used

8. Flunarizine (a calcium antagonist)

and methysergide are used in refractory

patients

2. Tension-type headache
 Overlap with migraine, mild to moderate in severity, bilateral and relatively featureless, with
tight band sensations, pressure behind the eyes, and bursting sensations.
 May be comorbid with depression.

3. Trigeminal autonomic Cephalalgias

 Unilateral trigeminal distribution pain (usually in the ophthalmic division of the nerve), side
locked headache.
 Prominent ipsilateral autonomic features- redness or tearing of the eye, nasal congestion or
even a transient Horner’s syndrome.

46
 Cluster headache Paroxysmal hemicrania SUNCT

 Male>female
 20-40years
 Worst pain known to humans
 Prefer to move about or rock
rather than remain still
 Attacks are shorter than
migraine, occur several times
per day, especially during sleep
 Clusters last 1–2 months, with
attacks most nights, and
typically recurring a year or
more later, often at the same
time of year
 Short-lasting unilateral
 Male <female
neuralgiform headache
 Attacks last -10–30 min
with conjunctival
 More frequent and do
injection and tearing
not occur in clusters
 Very rare
 Attacks -5 seconds to 2
minutes, and very
Complete response to
frequently occur in
Indometacin
bouts

Acute Tx-subcutaneous
sumatriptan drug of choice ,High
flow oxygen

Terminate the bouts of clusters -

Verapamil, lithium and/or a short
course of steroids

4. Chronic daily headache

 Headache in 15 or more days per month for at least 3 months.

 Primary headache disorders, particularly migraine, are responsible for the majority.
 Overuse of analgesic medication causes transformation of episodic headache into chronic daily
headache.

Secondary headache disorders

1. Idiopathic intracranial hypertension
 Due to reduced CSF resorption.
 Younger, overweight female, polycystic ovaries, (pregnant, OCP, certain drugs
tetracycline, vit A supplement).
 Presents with-
 Headache (present on waking and made worse by coughing,
straining or sneezing)
 Transient visual obscuration - florid papilloedema

47
  VI th nerve palsy– false localizing sign

Investigation:

LP- CSF opening pressure (elevated, with normal constituents).

NCCT brain- normal, ventricles may be small and appear ‘slit-like’.

Sagittal sinus thrombosis can cause a similar picture -to exclude -MR venography.

Management:

Self-limiting.

Longstanding severe papilloedema - Optic nerve damage - progressive loss of peripheral visual fields.
Regular monitoring of visual fields with perimetry is essential.

1. Emphazise on weight reduction.

2. Drugs redusing CSF production- acetazolamide and thiazide.

3. Therapeutic CSF tap.

4. Ventriculoperitoneal shunt insertion or optic nerve sheath fenestration to protect vision.

2. Low-CSF-volume(low-pressure) headache

Following LP, or spontaneously (history of vigorous Valsalva, straining or coughing just prior to
onset) - leading to postural headache, worse on standing or sitting and relieved completely by lying
flat.

Facial pain

Arise from teeth, gums, sinuses, temporomandibular joints, jaw and eyes.

Also caused by specific neurological conditions.

Trigeminal neuralgia

Starts in the 6&7decades.

HTN - main risk factor.

Younger patients- multiple sclerosis or a CP angle tumour (acoustic schwannomas, meningiomas,

epidermoids).

Clinical features:

 Paroxysms of knife-like or electric shock-like pain- in the distribution of the Vth

nerve- lasting seconds.
 Commence in the V3 spread over time to involve V2 and, V1.
 B/L – rare (demyelination)
 Episode occur many times/day with refractory period after each.

48
  Stimulation of trigger zones in the face (washing, shaving, a cold wind and chewing)-
provoke pain.
 No signs of Vth nerve dysfunction on examination.

Tx- Carbamazepine, Oxcarbazepine, lamotrigine and gabapentin- if not effective - surgical options

Giant cell arteritis (temporal arteritis)

Granulomatous large-vessel arteritis.

>50years

Clinical features:

1. Headache- develops over inflamed superficial temporal and/or occipital arteries. Combing the hair
causes pain. The artery becomes hard, tortuous and thickened result in loss of pulsation.

2. Facial pain- Pain in the face, jaw and mouth (inflammation of facial, maxillary and lingual branches
of ECA). worse on eating (jaw claudication), mouth opening and protruding the tongue. A painful,
ischaemic tongue occurs rarely.

3. Visual problem

Untreated cases  arterial inflammation and occlusion  ischemic optic neuropathy  sudden
mono ocular visual loss (complete or partial)

• Posterior ciliary artery occlusion - anterior ischaemic optic neuropathy -optic disc swollen
and pale, retinal branch vessels remain normal
• Central retinal artery occlusion- sudden permanent U/L blindness, disc pallor and visible
retinal ischaemia. B/L blindness may develop, with the second eye being affected 1–2
weeks after the first.

49
Brain Tumours

Benign 15% Malignant

 Meningioma Primary malignant tumours Metastases

 Neurofibroma of neuroepithelial tissues
50%
35%

 Astrocytoma  Bronchus
 Oligodendroglioma  Breast
 Mixed (oligoastrocytoma)  Stomach
glioma  Prostate
 Ependymoma  Thyroid
 Primary cerebral  Kidney
 Lymphoma
 Medulloblastoma

Gliomas

 Usually within the cerebral hemispheres, occasionally in the cerebellum, brainstem or cord.
 Occasionally associated with neurofibromatosis.
 Spread by direct extension, never metastasizing outside the CNS.

Astrocytomas Oligodendrogliomas

 Arise from astrocytes  Arise from oligodendrocytes

 Histological grades I–IV  Grow slowly ( over several decades)
 Grade 1-grow slowly  Calcification is common
 Grade IV (glioblastoma
multiforme) -cause death within
several months
 Cystic astrocytomas of
childhood -relatively benign and
usually cerebellar

Meningiomas

 Arise from the arachnoid.

 Grow to a large size- over years.
 Common sites – parasagittal region, sphenoidal ridge, subfrontal region, pituitary fossa and
skull base. Occur along the intracranial venous sinuses, which they may invade.
 Unusual below the tentorium.
 Can erode bone or cause local hyperostosis.

50
 Neurofibromas (schwannomas)
 Arise from Schwann cells.
 Occur in the CP angle (arise from the VIII th nerve sheath, acoustic neuroma).
 Bilateral in neurofibromatosis type 2.
Clinical features of brain tumours
Direct effects of mass lesions
Infiltration of brain matter--- local
progressive deterioration of function
Eg:
1. Left frontal meningioma-
Frontal lobe syndrome over several
years (disturbance of personality,
apathy and impaired intellect).
Expressive aphasia.
Progressive right hemiparesis-
involvement of corticospinal
pathway.
2. Left VIII th nerve sheath
neurofibroma (acoustic neuroma)—
Progressive deafness (VIII).
Left facial numbness (V) and
weakness (VII).
Cerebellar ataxia on the same side.
Secondary effects of raised Provocation of generalized
intracranial pressure and/or focal seizures
Headache, vomiting and Common presenting feature
papilloedema. of malignant brain tumours
unusual presentation of a mass Focal seizures, with or
lesion in the brain. without altered awareness
that may evolve into
Symptoms imply obstruction to CSF
bilateral tonic–clonic
pathways (hytrocephalus)
seizures, are characteristic
Produced early by posterior fossa of many hemisphere
masses, later by lesions above the masses.
tentorium.
Shift of the intracranial contents
produces:
1. Distortion of the upper brainstem
causes impairment of consciousness,
progressing to coning and death
2. False localizing signs-
VI th nerve lesion-first on the side of
a mass and later bilaterally.
III rd nerve lesion - as the temporal
lobe uncus herniates caudally, the
first sign is ipsilateral pupil dilatation
as parasympathetic fibres are
compressed.
3. Hemiparesis on the same side of
the tumour-compression of the
contralateral cerebral peduncle on
the edge of the tentorium.
51
Investigation:

1. CT and MRI are useful in detecting brain tumours; MRI is superior for posterior fossa lesions.

2. PET - to locate an occult primary tumour with brain metastases.

3. Lumbar puncture- contraindicated.

4. Biopsy and tumour removal.

Biopsy - to detect the histology of most suspected malignancies.

Benign tumour- symptomatic, accessible meningioma, craniotomy and removal are usual.

52
2. Kidney diseases

Renal functions

53
Urine analysis

Glomerular diseases
 Third most common cause (after diabetes and hypertension) of end- stage kidney disease
(ESKD) in Europe and USA

54
 Four major glomerular syndromes
o Nephrotic syndrome
o Glomerulonephritis (nephritic syndrome):
 Acute glomerulonephritis
 Rapidly progressive glomerulonephritis
o Mixed nephritic/nephrotic presentations
o Asymptomatic haematuria, proteinuria or both

55
 Nephrotic syndrome
 characterized by:
• hypoalbuminaemia
 Explained by increased catabolism of reabsorbed protein, largely albumin, in
the proximal tubules, even though the rate of albumin synthesis is increased.
• >3.5g proteinuria/day
 occurs partly because structural damage to the glomerular barrier (podocytes,
basement membrane, fenestrated endothelium and endothelial charge)
• dyslipidaemia
 a consequence of increased synthesis of lipoproteins as a direct consequence of
a low plasma albumin.
• salt and water retention, leading to oedema.

General management
• Monitor daily BW, input & output
• Dietary sodium restriction
• Normal protein intake

o A high- protein diet (80–90 g protein daily) increases proteinuria and can be harmful in
the long term.

56
 • Prophylactic anticoagulation

o Until serum albumin & nephrotic syndrome improves as hypercoagulable states (due to
loss of clotting factors in urine) predispose to venous thrombosis. Prolonged bed rest
should be avoided. Thromboembolism very common in membranous nephropathy.
• Assessment of volume state is important prior to diuretics
Patients are sometimes hypovolaemic, and moderate oedema may have to be accepted in
order to avoid postural hypotension.
• Diuretics
o may need intravenous therapy (Nephrotic patients may malabsorb diuretics owing to
gut mucosal oedema)
 Sepsis is a major cause of death. Increased susceptibility is partly due to loss of
immunoglobulin in the urine. Pneumococcal infections are particularly common and
pneumococcal vaccine should be given. Early detection and aggressive treatment of
infections is better, rather than long- term antibiotic prophylaxis.
 ACE inhibitors and/or ARBs are indicated for their antiproteinuric properties. Reduce
proteinuria by lowering glomerular capillary filtration pressure (a fall in efferent tone
decreases the transglomerular capillary pressure, and so protein loss into the urinary
space); BP and renal function monitored regularly.

Causes of nephrotic syndrome

• Primary

- Minimal change
- Focal segmental glomerulosclerosis
- Membranous nephropathy

• Secondary

- Diabetes mellitus
- Amyloidosis

57
Minimal-change nephropathy (minimal-change disease)

 Glomeruli appear normal on light microscopy.

 On electron microscopy, fusion of the foot processes of podocytes.
 Neither immune complexes nor anti- GBM antibody can be demonstrated by
immunofluorescence on glomerular staining for antibody.
 Immature differentiating CD34 stem cells are responsible for the MCN.
 NSAIDs, lithium, antibiotics (cephalosporins, rifampicin, ampicillin), bisphosphonates and
sulfasalazine have been implicated in MCN.
 Atopy is present in 30% and allergic reactions can trigger the nephrotic syndrome.
 Hepatitis C virus, HIV and tuberculosis, are rarer causes.

Clinical features

 most common in children, particularly boys and responsible for the large majority of cases of
nephrotic syndrome in childhood.
 condition accounts for 20–25% of cases of adult nephrotic syndrome.
 often regarded as a condition that does not lead to CKD.

Management

 Manage symptoms with general measures (see earlier).

 High-dose corticosteroid therapy with prednisolone reverses proteinuria in more than 95%
of children.
 Response rates in adults are significantly lower and response may occur only after many
months
 Spontaneous remission also occurs.
 second- line agent should be added after repeat induction with steroids, in regularly
relapsing patients.
o Ciclosporin or tacrolimus (Excretory function and ciclosporin and tacrolimus trough
blood levels must be monitored regularly, as both drugs are potentially
nephrotoxic.)
o Rituximab (a depleting monoclonal antibody directed against CD20 and present on B
lymphocytes)
o Cyclophosphamide ( side effects - azoospermia, premature ovarian failure)
o levamisole (anthelminthic agent)

Congenital nephrotic syndrome

 autosomal recessively inherited disorder due to mutations in the genes such as nephrin (a
critical element of the filtration slit),podocin, α- actinin 4 and Wilms’ tumour suppressor
gene.
 Gene mutation to nephrin is characterized by relentless progression to ESKD.

58
  Congenital nephrotic syndrome patients are steroid- resistant.

Focal segmental glomerulosclerosis

 Is a sclerotic glomerular lesion that affects some (but not all) glomeruli, and some (but not
all) segments of each tuft.
o Primary FSGS
o Secondary FSGS
 Primary focal segmental glomerulosclerosis
o Associated nephrotic syndrome is often resistant to steroid therapy.
o All age groups are affected.
o Usually recurs in transplanted kidneys.
o Aetiology - A circulating permeability factor causes the increased protein leak.
o Pathology - seen on light microscopy, which later progresses to global sclerosis. may
be missed on transcutaneous biopsy. A pathogenetic link may exist between MCN
and FSGS. Five histological variants of FSGS exist.
o Management - Prednisolone, Ciclosporin or tacrolimus (effective in reducing or
stopping urinary protein excretion. long- term use is required.) ,Cyclophosphamide,
chlorambucil or azathioprine ( used as second- line therapy in adults.)
o About 50% of patients progress to ESKD within 10 years of diagnosis, particularly
those who are resistant to therapy.
 Secondary FSGS
o Associations include:
• reduced nephron number (e.g. nephrectomy, hypertension, gross obesity,
ischaemia, sickle nephropathy, reflux nephropathy, chronic allograft nephropathy,
IgA nephropathy, and scarring following renal vasculitis)
• mutations in specific podocyte genes
• viruses, e.g. HIV type 1, erythrovirus B19, cytomegalovirus, Epstein–Barr virus and
simian virus 40
• drugs such as heroin, all interferons, anabolic steroids, lithium, sirolimus,
pamidronate and calcineurin inhibitors, e.g. ciclosporin
• APOL1 gene mutations

HIV-associated nephropathy
 glomeruli are characteristically ‘collapsed’ on light microscopy .
 Anti- retroviral therapy may reverse the renal lesions, if treatment is commenced
early.

Membranous glomerulopathy

 occurs mainly in adults and predominantly in men.

 one- third of patients undergo spontaneous or therapy- related remission. About 40%
develop CKD.
 Pathogenesis - Causes include:

59
 • drugs (e.g. penicillamine, gold, NSAIDs, probenecid, mercury, captopril)
• other autoimmune disease (e.g. SLE, thyroiditis)
• infections (e.g. hepatitis B, hepatitis C, schistosomiasis, Plasmodium malariae)
• cancers (e.g. carcinoma of the lung, colon, stomach, breast and lymphoma) •
other causes (e.g. sarcoidosis, sickle cell disease).
 On light microscopy, capillary loops appear thick. Using a periodic acid–Schiff or silver stain
‘spikes’ of basement membrane are visible.
 Management -
o one- third or more of patients will undergo spontaneous remission.
o All patients should receive ACE inhibition at the maximum tolerated dose,
anticoagulation, diuretics and a statin if indicated.
o Rituximab, an anti-CD20 antibody (which ablates B lymphocytes), is effective in
inducing remission.
o The alkylating agents cyclophosphamide and chlorambucil.
o Ciclosporin or tacrolimus
o Oral corticosteroids are of no benefit alone but may be additive.

Amyloidosis

 Amyloidosis is a systemic disorder of protein folding, in which normally soluble proteins or

fragments are deposited extracellularly as abnormal insoluble fibrils (usually β- pleated
sheets that are resistant to proteolysis), causing progressive organ dysfunction and death.
 Acquired or inherited.
 The most common forms are AL amyloidosis (where abnormal protein may be derived from
light chains or immunoglobulin) and AA amyloidosis (where deposits form from serum
amyloid A protein).
 Diagnosis -
o Often made clinically.
o On imaging, the kidneys are often large.
o Renal biopsy is necessary in all suspected cases of renal involvement.
 Management - Treatments that reduce production of the amyloidogenic protein can
improve organ function and survival. ( eg; Myeloma-directed therapy)

Diabetic nephropathy

 Leading cause of ESKD in the Western world, arising largely as a complication of type 2
diabetes mellitus.
 Occurs in about 20–30% of both type 1 and type 2 diabetics.
 Risk factors for nephropathy include poor glycaemic control, hypertension, male gender,
ethnicity and social deprivation.
 Pathology -
o Glomerular hyperfiltration (the GFR increases to >150 mL/min per m2) and initial
enlargement of kidney volume occur as local vasoactive factors increase flow.
o Progressive depletion of podocytes from the filtration barrier.
o Proteinuria evolves as filtration pressures rise and the filter is compromised.

60
 oLater, glomerulosclerosis develops with nodules (Kimmelstiel–Wilson lesion) and
hyaline deposits in the glomerular arterioles.
 Management -
o Lifestyle changes (cessation of smoking, attention to salt intake, weight loss and
increased exercise) are necessary to prevent progression.
• Aim for good (intensive) glycaemic control - this reduces the incidence of ESKD
and other microvascular complications in the long term, SGLT2 inhibitors
(dapagliflozin, canagliflozin and empagliflozin) and GLP- 1 agonists such as
liraglutide, semaglutide and dulaglutide have specific cardiac and renoprotective
effects.
• Control dyslipidaemia.
• Control blood pressure to <130/80 mmHg with ACE inhibitors or AII- RAs
Other interventions- Pentoxyphylline, Atrasentan

Isolated proteinuria without haematuria

 In asymptomatic patients often an incidental finding.
 Over 50% of these patients have (benign) postural proteinuria.
 may be an early sign of a serious glomerular lesion.
 Mild and transient proteinuria may also accompany a febrile illness,
congestive heart failure or infectious diseases with no clinical renal
significance.

Glomerulonephritis (asymptomatic, acute and rapidly progressive)

• Glomerulonephritis (GN) is immunologically mediated, with involvement of cellular immunity (T-
lymphocytes, macrophages/dendritic cells), humoral immunity (antibodies, immune complexes,
complement) and other inflammatory mediators (including cytokines, chemokines and the
coagulation cascade).
• The immune response can be directed against known target antigens, particularly when GN
complicates infections, cancers or drugs.
• The underlying antigenic target is more often unknown.
• Primary GN may occur in genetically susceptible individuals following environmental insults.

GN may present as:

• Asymptomatic urinary abnormalities

• Acute nephritis (nephritic syndrome)

• Rapidly progressive glomerulonephritis.

(The same underlying histology may often present in any of these ways, and these should be seen as
clinical syndromes on a spectrum rather than as distinct diseases.)

61
Asymptomatic urinary abnormalities
Haematuria with or without sub--nephrotic--range proteinuria in an asymptomatic patient may lead
to the early discovery of potentially serious glomerular disease such as SLE, Henoch–Schönlein
purpura, post--infectious GN or idiopathic hypercalciuria in children.

Acute nephritis (nephritic syndrome)

This classically presents as:

• haematuria (macroscopic or microscopic) – with red--cell casts on urine microscopy

• proteinuria
• hypertension
• oedema (periorbital, leg or sacral)
• temporary oliguria and uraemia.

Nephritis is usually distinguished from rapidly progressive glomerulonephritis by the lack of cellular
necrosis (and crescent formation) in the glomeruli seen on biopsy, and the rate at which renal
decline evolves.

Rapidly progressive glomerulonephritis

Is a syndrome with glomerular haematuria (red blood cell casts or dysmorphic red blood cells),
rapidly developing acute kidney failure over weeks to months and focal glomerular necrosis with or
without glomerular crescent development on renal biopsy.

• RPGN can develop with immune deposits (anti--GBM or immune complex type, e.g. SLE) without
immune deposits (pauci--immune, e.g. anti--proteinase 3 (PR3) and or anti--myeloperoxidase–
antineutrophil cytoplasmic antibodies (MPO--ANCA)--positive vasculitides).

• It can also develop as an idiopathic primary glomerular disease, or secondary glomerular diseases
such as IgA nephropathy, membranous GN and post--infective GN.

• It can be classified based on the pattern of immune complex deposition in glomeruli (seen on
immunofluorescence): that is, linear, granular and negative immunofluorescent patterns.

62
Post--streptococcal glomerulonephritis

Occurs in childhood.

An acute nephritis follows 1–3 weeks after a streptococcal infection. Streptococcal throat infection,
otitis media or cellulitis can all be responsible.

The infecting organism is a Lancefield group A β-haemolytic streptococcus of a nephritogenic type.

The latent interval between infection and the development of symptoms and signs of renal
involvement reflects the time taken for immune complex formation and deposition and glomerular
injury to occur.

PSGN is now rare in developed countries.

Renal biopsy shows diffuse, florid, acute inflammation in the glomerulus with neutrophils and
deposition of IgG and complement similar biopsy findings may be seen in non--streptococcal post-
-infectious glomerulonephritis

Management Aim

• Good blood pressure control

• Diuretics and salt restriction for oedema
• Dialysis as necessary.
• If recovery is slow, corticosteroids may be helpful.

The prognosis is usually good in children.

A small number of adults develop hypertension and/or CKD later in life. (So an annual blood
pressure check and measurement of serum creatinine are required).

Evidence in support of long--term penicillin prophylaxis after the development of GN is lacking.

63
In non--streptococcal post--infectious GN, prognosis is equally good if the underlying infection is
eradicated.

Glomerulonephritis with infective endocarditis

● GN occurs rarely in patients with infective endocarditis or infected ventriculoperitoneal

shunts (shunt nephritis).
● Histological appearances resemble those of post--infectious GN but lesions are usually focal
and segmental.
● Crescentic GN with AKI has been described, particularly with Staphylococcus aureus
infection.
● Appropriate antibiotic therapy or surgical eradication of infection in fulminant cases usually
results in a return of normal renal function.
● GN also occurs in association with visceral abscesses (mainly pulmonary) and is
indistinguishable from post--infectious GN. Complement levels are normal and immune
deposits are absent on biopsy.
● Antibiotic therapy and surgical drainage of the abscess result in complete recovery of renal
function in approximately 50% of patients.

IgA nephropathy

● IgA nephropathy has replaced PSGN as the most common form of GN worldwide.
● Demographic and family studies support the existence of a genetic contribution to the
pathogenesis of IgA nephropathy but results from genetic association studies of candidate
genes are inconsistent.
● A genome--wide analysis study conducted in European patients showed a strong association
on chromosome 6p in the region of the MHC/DQ and HLA--B loci.

Histology

● There is a focal and segmental proliferative GN with mesangial deposits of polymeric IgA1.
● In some cases, IgG, IgM and C3 are also seen in the glomerular mesangium.
● The features have prognostic significance and should be taken into account for predicting
outcome independent of the clinical features, both at the time of presentation and during
follow--up.

Several diseases are associated with IgA deposits, including Henoch–Schönlein purpura, chronic liver
disease, malignancies (especially carcinoma of bronchus), seronegative spondyloarthritis, coeliac
disease, mycosis fungoides and psoriasis.

64
Clinical features

● IgA nephropathy tends to occur in children and young males

● Presenting with asymptomatic microscopic haematuria or recurrent macroscopic
haematuria following an upper respiratory or gastrointestinal viral infection.
● Proteinuria occurs and 5% of cases can be nephrotic.
● The prognosis is usually good, especially in those with normal blood pressure, normal renal
function and absence of proteinuria at presentation.
● Recurrent macroscopic haematuria is a good prognostic sign, although this may be due to
‘lead-­time bias’
● The risk of eventual development of ESKD is about 25% in those with proteinuria of more
than 1 g per day, elevated serum creatinine, hypertension, ACE gene polymorphism (DD
isoform) and tubulointerstitial fibrosis on renal biopsy.

Management

● All patients, with or without hypertension and proteinuria, should receive an ACE inhibitor
or an AII--RA, to reduce proteinuria and preserve renal function.
● Patients with proteinuria of >1–3 g/day, mild glomerular changes and normal renal function
may be treated with steroids, aiming to reduce proteinuria and stabilize function
● In patients with higher--risk progressive disease with proteinuria of >750 mg/day and eGFR
falling to <60 mL/min, prednisolone alone or with cyclophosphamide for 3 months, followed
by maintenance with prednisolone, has failed to demonstrate any benefit.
● Tonsillectomy can reduce proteinuria and haematuria in those with recurrent tonsillitis.

Alport’s syndrome

● Is a rare hereditary nephritis with haematuria, proteinuria (<1–2 g/day), progressive kidney
disease and high-frequency nerve deafness.
● Approximately 15% of cases may have ocular abnormalities, such as bilateral anterior
lenticonus, and macular and perimacular retinal flecks.
● In about 85% of patients with Alport’s syndrome there is an X--linked inherited mutation in
the gene encoding collagen chain, a critical component of the GBM.
● Defective monomers are rapidly degraded. Over time the basement membrane undergoes
selective proteolysis, and glomerular membranes thicken unevenly, split and ultimately
deteriorate.
● Although the basement membrane is abnormal, podocyte function and the slit diaphragm
are unaffected, and so proteinuria in Alport’s syndrome is often mild and is the result of
glomerular sclerosis, rather than primary loss of slit

Management

● The disease is progressive and accounts for some 5% of cases of ESKD in childhood or
adolescence.

65
 ● Patients with mild CKD can be treated with ACE inhibitors to attenuate proteinuria.

Thin GBM disease

● This condition is inherited in autosomal dominant fashion.

● Typically presents with persistent microscopic glomerular haematuria
● The diagnosis is made on renal biopsy, which shows thinning of the glomerular capillary
basement membrane on electron microscopy.
● The prognosis for renal function is usually very good but some patients develop renal
insufficiency over decades.
● No treatment is of known benefit.

Anti--GBM glomerulonephritis

● Characterized by linear capillary loop staining with IgG and C3 and extensive crescent
formation, accounts for 15–20% of all cases of RPGN
● Overall represents less than 5% of all forms of GN.
● This condition is rare, with an incidence of 1 per 2 million in the general population.
● About two-­thirds of these patients have Goodpasture’s syndrome with associated lung
haemorrhage
● Anti--GBM antibodies (detected by enzyme--linked immunosorbent assay, or ELISA) are
present in serum and are directed against the non-­collagenous (NCl) component of α3 (IV)
collagen of the basement membrane.
● The mechanism of renal injury is complex.
● When anti--GBM antibody binds basement membrane, it activates complement and
proteases, and results in disruption of the filtration barrier and Bowman’s capsule, causing
proteinuria and the formation of crescents.

Management

● Plasma exchange to remove circulating anti--GBM antibodies

● Steroids to suppress inflammation from antibody already deposited in the tissue
● Cyclophosphamide to suppress further antibody synthesis.
● The prognosis is directly related to the extent of glomerular damage at the initiation of
treatment. When oliguria occurs or serum creatinine rises above 600−700 ´mol/L, renal
failure is usually irreversible.
● Once the active disease is treated, this condition, unlike other autoimmune diseases, does
not follow a remitting/relapsing course.

ANCA--positive small--vessel vasculitis

● Inflammation and necrosis of the blood vessel wall occurs in many primary vasculitic
disorders.
● The small--vessel vasculitides affecting the kidney include:

66
• granulomatosis with polyangiitis (GPA)
• microscopic polyangiitis (MPA)
• renal--limited vasculitis (without systemic features)
• eosinophilic granulomatosis with polyangiitis (which is frequently ANCA--negative)

• The ANCA--associated small--vessel vasculitides are GPA, MPA and renal--limited vasculitis.
• GPA and MPA share a common pathology with focal necrotizing lesions, which affect many
different vessels and organs:
o in the lungs, cause lung haemorrhage
o within the glomerulus of the kidney, crescentic GN and/or focal necrotizing lesions
may cause AKI
o in the dermis cause purpuric rash or vasculitic ulceration.

• Renal histology is regarded as a ‘gold standard’ for diagnosis and prognostication of ANCA-
-associated GN.

Pathogenesis

• There are two forms of ANCA, PR3--ANCA (cANCA) and MPO--ANCA (pANCA).
• If ELISA and indirect immunofluorescence techniques are combined, diagnostic specificity is 99%.
• ANCA and anti--GBM antibodies do occur together; such patients tend to follow the natural
history of Goodpasture’s syndrome.

Management

● The sooner treatment is instituted, the greater chance there is of recovery of renal function.
● High--dose oral corticosteroids and intravenous pulsed cyclophosphamide are of benefit in
inducing remission.
● The best indicators of adverse prognosis are pulmonary haemorrhage and severity of renal
failure at presentation.
● Rituximab is equally effective in inducing remission in ANCA-associated vasculitides in the
short term (6–12 months), with similar adverse event rates.
● Rituximab may be a therapeutic option in patients who cannot tolerate cyclophosphamide,
and in those whose disease is poorly controlled and who relapse while on
cyclophosphamide.

● Fulminant disease requires intensification of immunosuppression with adjuvant plasma

exchange or intravenous pulsed methylprednisolone

● Once remission has been achieved, azathioprine can be substituted for cyclophosphamide,
which was more effective than mycophenolate.
● Use of rituximab every 3 months in fixed dose has been shown to be superior to
azathioprine in the maintenance of remission.

67
Mixed nephritic and nephrotic syndrome

Injury involves mesangial cells, endothelium, the basement membrane and podocytes in this
heterogeneous group of conditions.

Mesangiocapillary (membranoproliferative) glomerulonephritis

• Is an uncommon descriptive lesion that has three subtypes with similar clinical presentations:
nephrotic syndrome, haematuria, hypertension and renal impairment. They also produce similar
microscopic findings, although the pathogenesis may be different.
• Electron microscopy defines:
o Type 1 MCGN:
o Type 2 MCGN, or C3 nephropathy
o Type 3 MCGN has features of both type 1 and type 2 disease.
• Complement activation appears to be via the final common pathway of the cascade.

• Most patients eventually go on to develop ESKD over several years.

Management

● In idiopathic MCGN (all age groups) with normal renal function and non-nephrotic-range
proteinuria, no specific therapy is required.
● Good blood pressure control, ideally with an ACE inhibitor, is of benefit.
● In children with the nephritic syndrome and/or impaired renal function, a trial of steroids
may be warranted (alternate-day prednisolone 40 mg/m2 for a period of 6–12 months). If no
benefits are seen, the treatment should be stopped.

● Regular follow-up, with control of blood pressure, use of agents to reduce proteinuria and
correction of lipid abnormalities, is necessary.

● In adults with the nephritic syndrome and/or renal impairment, aspirin (325 mg) or
dipyridamole (75–100 mg) daily, or a combination of the two, may be given for 6–12
months.
● Again, if no benefits are seen, the treatment should be stopped.

Systemic lupus erythematosus (lupus nephritis)

● Overt renal disease occurs in at least one-third of systemic lupus erythematosus (SLE)
patients and, of these, 25% reach ESKD within 10 years.
● Histologically, almost all patients will have changes.
● Box 36.16 shows the progression of the histological findings and the clinical picture from
classes I to VI.

68
● Serial renal biopsies show that in approximately 25% of patients, histological appearances
change from one class to another during the inter-biopsy interval.
● Immune deposits in the glomeruli and mesangium are characteristic of SLE and stain
positive for IgG, IgM, IgA and the complement components C3, C1q and C4 on
immunofluorescence.
● Pathophysiology SLE is known to be a multifactorial autoantigen-driven, T-cell-dependent
and B-cell-mediated autoimmune disorder.
● Lupus nephritis typically associates with multiple circulating autoantibodies to cellular
antigens (particularly anti-dsDNA, anti-Ro) and with complement activation, which leads to
reduced serum levels of C3, C4 and (particularly) C1q.

Management

● Initial management depends on the clinical presentation but hypertension and oedema
should always be treated.
● Disease activity, kidney biopsy and histology, as well as the presence or absence of
extrarenal manifestations of lupus, guide therapy.
● Type I 》》 no specific treatment.
● Type II 》》 usually runs a benign course but some patients are treated with
hydroxychloroquine and/or steroids alone.
● There have been a number of clinical trials with immunosuppressive agents in types III, IV
and V lupus nephritis.
● Outcomes are affected by ethnicity, clinical characteristics, irreversible damage (on renal
biopsy), initial response to treatment and the future frequency of renal flares.
● Steroids and high-dose intravenous cyclophosphamide or mycophenolate mofetil (MMF)
may be used as induction therapy.
● Remission is maintained with MMF (superior to azathioprine) or azathioprine, which is
similar in effectiveness to ciclosporin in reducing the risk of relapses.
● B-cell depletion with rituximab (anti-CD20) has been used in some patients, with favourable
results over the short term.

69
 Prognosis

● Treatment leading to the normalization of proteinuria, hypertension and renal dysfunction

indicates a good prognosis.
● The prognosis is better in patients with types I, II and V disease.
● Glomerulosclerosis (type VI) usually predicts ESKD.

■ IgM nephropathy

■ C1q nephropathy

■ Monoclonal gammopathy of renal significance

■ Idiopathic fibrillary glomerulopathy

■ Immunotactoid glomerulopathy

■ Fibronectin glomerulopathy

■ Cryoglobulinaemic renal disease

■ Immunoglobulin A vasculitis (Henoch-Schonlein syndrome)

Other glomerular disorders

● Fabry’s disease
● Sickle nephropathy
● Glomerulopathy associated with pre-eclampsia
● Paraneoplastic glomerulonephritis

Tubular interstitial nephritis

Acute tubular interstitial nephritis

 Drug induced – asymptomatic or with fever, arthralgia skin rashes and acute oliguric
May have eosinophilia or eosinophilicuria
Caused by NSAIDs
Tx- stop offending agent, high dose prednisolone

 Infection induced- Acute pyelonephritis related or systemic infections like EBV,HIV,

measles, hanta virus, or legionella , leptospira, streptococci
Tx- Eradiation of infection, renal transplantation, immunosuppressive agents

70
 Chronic tubulointerstitial nephritis

Tx- Discontinuation of offending agent, Treat underlying disease , hydration , if need renal
replacement therapy

UTI
Natural history – single attack 90%

Recurrent attacks -10%

 Relapse 20%
 Re infection 80%

Organisms –

 E.coli 70%
 Proteus 12%
 Staphylococcus saprophyticus or epidermidis 10%

Diagnostic criteria

 Symptomatic young patient - > 102 coliform organisms/ml plus pyuria or > 105 any
pathogenic organism/ ml of urine or any growth of pathogenic organisms in urine by
suprapubic aspiration.
 Symptomatic men > 103 pathogenic organisms/ml of urine
 Asymptomatic patients - > 105 pathogenic organisms/ml urine on 2 occasions.

Risk factors

 Female gender
 Sexual activities
 Indwelling catheter
 Urinary tract stones
 Urine tract stasis
 DM

71
Clinical features

 Increase in frequency
 Dysuria
 Hematuria
 Smelly urine
 Suprapubic pain and tenderness

Acute pyelonephritis – Fever, loin pain with tenderness and significant bacteriuria

Investigations

 UFR
 Urine culture and ABST
 USS –calculi,obstruction,tract abnormalities, incomplete bladder emptying
 CT – to diagnosis of complicated UTI

Management

 Appropriate antibiotics (according to the local antibiotic guideline)

 High fluid intake (2L per day )

Recurrent UTI Mx-relapse – look for the course and treat

Re infection- High fluid intake, frequent voiding, voiding before bedtime and after
intercourse, avoid constipation.

72
Chronic Kidney disease
 Deterioration of renal functions and structure for >3months

Staging of CKD

73
 Complications of CKD

 Anemia – Due to erythropoietin deficiency, Increase in blood loss , BM toxins,

Hematinic deficiency, Increased in destruction of RBC due to uremia, ACE inhibitors
Mx-Synthetic or recombinant EPO, Fe B12 supplementation, Treat
underlying disease,
 Bone disease- renal osteodystrophy, Due to changes in calcium , phosphorous,
vitamin D metabolism – hyperparathyroid bone disease, osteomalacia,osteoporosis,
osteosclerosis, adynamic bone disease
Mx –dietary restriction of phosphate, phosphate binders, vitamin D
analogues, calcimimetic agents
 Cardiovascular disease- Risk factors- HTN, DM, DL, smoking ,Male gender- systolic
and diastolic dysfunction and coronary artery diseases
Mx- antioxidants, management of risk factors
 Pericarditis
 Skin disease-Due to accumulation of nitrogenous waste product,hypwecalcemia and
hyperphosphertimia,fe deficiency, hyperparathyroidism
Mx- aqueous cream for dry skin, inhibitors of porphyrin metabolism
 Gastrointestinal complication- decreased gastric emptying and reflux esophagitis,
peptic ulceration, acute pancreatitis
 Metabolic abnormalities- Gout –Mx – colchicine and reduction of allopurinol dose
Insulin- metabolism is reduced, and gluconeogenesis is
diminished
Lipid metabolism – impaired clearance,
hypercholesterolemia
 Endocrine abnormalities- hyperprolactinemia, decreased testosterone levels,
menstrual irregularities ,complex abnormalities of growth hormone secretion,
hypothyroidism

Management of CKD
 Address cardio vascular risk factors
 Avoid nephrotoxic drugs
 Close follow up
 Treat complications
 Renal replacement therapy

Acute kidney injury

 An abrupt deterioration in renal function, over hours or days
 Usually (not always) reversible
 Recognized by a falling urine output and rising serum urea and creatinine, or both.

74
Result from
 pre-renal causes (reduced kidney perfusion leads to a falling GFR
Falling renal blood flow leads to a falling GFR due to changes in the circulation, or to
intrarenal vasomotor changes that drop glomerular perfusion pressures
E.g.
1. Hypovolaemia
 Dehydration
 Reduced intake (nil by mouth, confusion)
 Gut losses (vomiting, nasogastric tube losses, diarrhoea)
 Renal losses (diuretics, hyperglycaemia)
 Burns, sweating
 Haemorrhage
 Third space losses (pancreatitis, peritonitis, bowel obstruction)
 Systemic vasodilation (septic shock, cirrhosis)
 Cardiac failure or shock

2. Hypotension without hypovolaemia,

 cirrhosis or
 septic shock
3. Low cardiac output
 Cardiac failure
 Cardiogenic shock
4. Combination of above
 renal parenchymal disorders (injury to glomerulus, tubule or vessels)
 Acute tubular necrosis
Occurs due to sustained under-perfusion and reduced renal blood flow of renal
tubules, leading to tubular cell death, or nephrotoxins causing direct injury and cell
death in renal tubules.
 post-renal causes
 Urinary tract obstruction –back-pressure affecting function (BPH, Stones, tumours
etc)

RIFLE classification

Proposed by The Acute Dialysis Quality Initiative group to define AKI, using either an increase in
serum creatinine or a decrease in urine output.

Renal dysfunction - Risk, Injury, Failure

Outcome measures - Loss, End stage

KDIGO (Kidney Diseases: Improving Global Outcomes) classification

Epidemiology

 1 in 5 adults and 1 in 3 children worldwide experience AKI during a hospital episode of care
 25% of patients with sepsis and 50% of patients with septic shock will have AKI.

75
Investigations

 Clinical assessment to Diagnose pre renal, renal or post renal?

Assess fluid status
Exclude bladder out flow tract obstruction (by catheterization or USS)
 Urinalysis
 Urine microscopy for red cells and red-cell casts (indicative of glomerulonephritis)
 Urine culture.
 Urine-for free haemoglobin and myoglobin
 uPCR - helpful in parenchymal disease
 Serum creatinine
 serum urea
 serum electrolytes, calcium, phosphate,
 albumin, alkaline phosphatase, urate concentrations
 Full blood count and examination of the peripheral blood film where necessary.
 Coagulation studies
 blood cultures and
 measurements of nephrotoxic drug blood levels

To differentiate acute vs chronic uremia consider,

1. History and duration of symptoms
2. Previous urinalysis or renal function test report
3. USS – ( size small and scarred in CKD except in DM and amyloidosis, & echogenicity
increased in CKD)
4. Anaemia of chronic disease, hyperparathyroidism or renal osteodystrophy suggests CKD.

76
Management

General measures

1. Good nursing
2. Treat the cause
3. Fluid balance and measure intake and output
Pre Renal
 Depends on the underlying cause. Commonest cause- hypovolaemia
 prompt fluid resuscitation is needed
 Crystalloids are used- eg. Ringer’s Lactate, plasmalyte (normal saline can cause
hyperchloraemic acidosis)
 Colloids such as hydroxyethyl, starch are contraindicated, can worsen AKI
 Monitor pulse rate, volume and blood pressure frequently
 The use of intravenous mannitol, frusemide or ‘renal-dose’ dopamine is not supported
in management of AKI.
4. Daily measurements of weight and lying and standing blood pressure
5. Medication review to withhold nephrotoxins,
6. collateral history and analyze past results
Specific measures

1. hyperkalemia
2. pulmonary oedema
3. sepsis
4. avoid use of nephrotoxin drugs
5. fluid and electrolyte balance
6. nutrition - salt and potassium restriction
7. Renal replacement therapy- haemodialysis and haemofiltration, or peritoneal dialysis
The main indications for blood purification and/or fluid removal are: (indications for hemodialysis)

 symptomatic uraemia (including pericarditis or tamponade)

 hyperkalaemia not controlled by conservative measures
 pulmonary oedema unresponsive to diuresis
 severe acidosis
 For removal of drugs causing the AKI, e.g. gentamicin, lithium, severe aspirin overdose.
Other causes of AKI

1. Rhabdomyolysis
 Skeletal muscle injury provokes the release of intracellular myoglobin, which is a direct
tubular toxic. Rapid rises in potassium, phosphate and lactate accompany elevated muscle
enzymes (aspartate aminotransferase, AST) and creatine phosphokinase (CK) is massively
elevated.
 Early and vigorous fluid resuscitation is necessary
 similar syndrome can arise with massive haemolysis, where the tubular toxin is
haemoglobin rather than myoglobin
2. Acute cortical necrosis

77
  Renal hypoperfusion results in diversion of blood flow from the cortex to the medulla, with
a drop in GFR cause Glomerular scarring (Glomerulosclerosis)
 Any cause of ATN, if sufficiently severe or prolonged, may lead to cortical necrosis.
3. Contrast nephropathy
 Dose dependent
 Prevention –
 Stop metformin if creatinine is over 130´ μmol/L and not restarted until renal function
returns to the baseline level.
 Minimize the dose of contrast administered and adequate hydration.
 N-acetylcysteine given 48 h prior to radiological intervention
 Dopamine, theophylline (an adenosine antagonist) and prophylactic haemodialysis
(removing contrast agent from the circulation) are of no benefit.
4. Acute phosphate nephropathy
 Commonly due to administration of oral sodium phosphate solution as bowel
preparation for gastrointestinal investigations
5. Tumour lysis syndrome
 Due to rapid death of malignant cells, causes release of intracellular and membrane
products, including uric acid, potassium and phosphate
 Prevented by good hydration and allopurinol which prevents uric acid formation
6. Hepato renal syndrome
 Due to profound renal vasoconstriction with histologically normal kidneys

PCKD
AD PCKD most common inherited renal disease.

Mutation – PKD1- Chromosome 16 -85% of cases

PKD2- Chromosome 4

From 2nd decade onwards – loin pain, haematuria, Subarachnoid hemorrhages, Complications of
HTN, Complications of liver cysts, symptoms of uraemia and /or anaemia associated with CKD, Renal
calculi, Mitral valve prolapse

Diagnosis- By USS

Management- no definitive therapy yet

Vasopressin receptor antagonists-reduce the cyst growth and slow the rate of progression of renal
failure

Octreotide-halting the growth of both liver and renal cysts.

Medullary cystic disease.

Juvenile nephropathies- AR inheritance

Polyuria, polydipsia and growth retardation

Diagnosis by family Hx and renal Bx

78
 Medullary sponge disease

U/L or B/L

Intermittent renal colic,hematuria and passage of small stones

Medullary area has sponge like appearance

CT or IVU is diagnostic

Treatment for obstructive nephropathy due to stones.

Renal tubular acidosis

Inherited Channelopathies

Features Gitelman’s syndrome Bartter Syndrome Liddle’s syndrome

Inheritance AR AR AD
symptoms Nonspecific/ Polyuria/ polydipsia/ Non-specific/weakness
musculoskeletal FFT/seizures tetany fatigue/ Hypertension
/chondrocalcinosis features
Biochemical Hypochloremia Hypochloremia Hypernatremia/hypoka
hypokalemic alkalosis, hypokalemic lemic alkalosis/ low
Hypomagnesaemia/increas alkalosis, increased renin: aldosterone ratio
ed renin: aldosterone ratio renin: aldosterone
ratio/

79
urine Low calcium High calcium Normal calcium
treatment K/Mg replacement /K+ K replacement /K+ Low salt diet
sparing diuretics sparing diuretics amiloride

3. Endocrinology

Hypopituitarism
Multiple deficiencies usually result from tumor growth or other destructive lesions.GH and
gonadotrophins are usually first affected.

Panhypopituitarism is the deficiency of all anterior pituitary hormones. It is most commonly caused
by pituitary tumors, surgery or radiotherapy.

Clinical features of hypopituitarism

80
  Secondary hypothyroidism, hypoadrenalism, hypogonadism
and GH deficiency lead to tiredness and general malaise and
reduced quality of life.
 Hypothyroidism causes weight gain, slowness of thought and
action, dry skin, cold intolerance, constipation and potentially
bradycardia and hypothermia.
 Hypoadrenalism causes mild hypotension, hyponatraemia and,
ultimately, cardiovascular collapse during severe intercurrent
stressful illness.
 Hypogonadism leads to loss of libido, loss of secondary sexual
hair, amenorrhoea and erectile dysfunction and, eventually, osteoporosis.
 Hyperprolactinaemia may cause galactorrhoea and hypogonadism, including amenorrhoea.
 GH deficiency causes growth failure in children, and impaired
wellbeing in some adults.
 Weight gain (due to hypothyroidism; see above), or weight loss
in severe combined deficiency.
 Longstanding panhypopituitarism gives the classic picture of
pallor with hairlessness (‘alabaster skin’).

Investigations

Each axis of hypothalamic-pituitary system requires separate investigations.

Management

Glucocorticoid and thyroid hormones are essential for life. Both are given as oral replacement drugs,
hydrocortisone and levothyroxine respectively, as in primary thyroid and adrenal failure, with the
aim of restoring the patient to clinical and biochemical normality.

81
Sex hormone replacement is with testosterone in males and a combination of oestrogen and
progestogen in females, both for symptomatic control and for prevention of long-term problems
related to deficiency (e.g. osteoporosis).

When fertility is desired, gonadal function is stimulated directly by HCG or indirectly by pulsatile
GnRH.

In GH deficiency in children, if the adolescent remains deficient at the achievement of adult height,
GH replacement therapy can be offered until patients reach their mid-twenties to maximize muscle
and bone mass. In adult GH deficiency, GH replacement therapy also produces improvements in
body composition, work capacity and psychological wellbeing, together with reversal of lipid
abnormalities associated with high cardiovascular risk, and often results in significant symptomatic
benefit.

82
Thyroid axis

Hypothyroidism

83
Autoimmune (atrophic) hypothyroidism is the most common cause of hypothyroidism. It is
associated with anti-thyroid antibodies, leading to lymphoid infiltration of the gland and eventual
atrophy and fibrosis.

Autoimmune hypothyroidism is more common in females. Associated with other autoimmune

diseases.

Hashimoto’s thyroiditis is again more common in women and in late middle age. Gland is usually
firm and rubbery. TPO antibodies are present. There can be initial toxic phase called “Hashi-
Toxicity”. Later can be hypothyroid or euthyroid.

Postpartum thyroiditis is a transient phenomenon observed following pregnancy. Histologically it is a

lymphocytic thyroiditis. Postpartum thyroiditis may be misdiagnosed as postnatal depression.

Clinical features

Investigations

Serum TSH is the investigation of choice; a high TSH level confirms primary hypothyroidism. A low
free T4 level confirms the hypothyroid state.

Thyroid and other organ-specific antibodies may be present.Other abnormalities include the
following:

 anaemia, which is usually normochromic and normocytic in type but may be macrocytic
(sometimes this is due to associated pernicious anaemia) or microcytic (in women, due to
menorrhagia or undiagnosed coeliac disease).
 increased serum aspartate transferase levels, from muscle and/or liver.
 increased serum creatine kinase levels, with associated myopathy

84
  hypercholesterolaemia and hypertriglyceridaemia
 hyponatraemia due to an increase in ADH and impaired free water clearance.

Management

Replacement therapy with levothyroxine (thyroxine, i.e. T4) is given for life.

The aim is to restore T4 and TSH to well within the normal range.Adequacy of replacement is
assessed clinically and by thyroid function tests after at least 6weeks on a steady dose.

Hyperthyroidism

85
86
Graves disease

Most common cause of hyperthyroidism.

Serum IgG antibodies bind to TSH receptors in the thyroid stimulating thyroid hormone production.

Thyroid eye disease is a feature of Graves’ disease. It may accompany the hyperthyroidism in many
cases but patients may also be euthyroid or hypothyroid.

The natural history is one of fluctuation, many patients showing a pattern of alternating relapse and
remission; perhaps only 40% of subjects have a single episode. Many patients eventually become
hypothyroid.

Solitary toxic nodule is the cause for about 5% of the cases.

Toxic multinodular goiter commonly occurs in older women.

De Quervain’s thyroiditis is transient hyperthyroidism from an acute inflammatory process, probably

viral in origin. There is usually fever, malaise and pain in the neck with tachycardia and local
thyroid tenderness. ESR and plasma viscosity are raised, and thyroid uptake scans show suppression
of
uptake in the acute phase. Treatment of the acute phase is with aspirin, using short-term
prednisolone in severely symptomatic cases.

87
History and examination

 The eye signs – lid lag and ‘stare’ – may occur with hyperthyroidism of any cause but other
features of thyroid eye disease occur only in Graves’ disease.
 Graves’ dermopathy is rare and can occur on any extensor surface. Pretibial myxoedema is
the most commonly described and is an infiltration of the skin on the shin. Thyroid
acropachy is very rare and consists of clubbing, swollen fingers and periosteal new bone
formation.
 In the elderly, a frequent presentation is with atrial fibrillation, other tachycardias and/or
heart failure
 Children frequently present with excessive height or excessive growth rate, or with
behavioural problems such as hyperactivity. They may also show weight gain rather than
loss.

Investigations

 Serum TSH is suppressed in hyperthyroidism.

 A raised free T4 or T3 confirms the diagnosis; T4 is almost always raised but T3 is more
sensitive.
 TSH receptor stimulating antibodies (TSHR-Ab) are 97–99% specific for Graves’ disease.
 Thyroid peroxidase (TPO) and thyroglobulin antibodies are present in 80% of cases of
Graves’ disease.
 Scintiscan 99Tm is used in patients who are antibody negative to look for toxic nodular
disease.

Management

Three possibilities are available: anti-thyroid drugs, radio-iodine and surgery.

Anti-thyroid drugs

Carbimazole and Propylthiouracil are used frequently. These drugs inhibit the formation of thyroid
hormones and also have other minor actions; carbimazole is also an immunosuppressive
agent.

As many of the manifestations of hyperthyroidism are mediated via the sympathetic system, beta-
blockers are used to provide rapid partial symptomatic control; they also decrease peripheral
conversion of T4 to T3.

The major side-effect of drug therapy is agranulocytosis, which occurs in approximately 1 in 1000
patients, usually within 3 months of treatment. All patients must be warned to seek immediate
medical attention and to have a check of their white blood cell count if they develop unexplained
fever or sore throat.

88
Radioactive iodine

Radioactive iodine (RAI) can be given to patients of all ages, although it is contraindicated in
pregnancy and while breast-feeding.

It accumulates in the thyroid and destroys the gland by local radiation, although it takes several
months to be fully effective.

Patients must be rendered euthyroid before treatment.

Surgery

Thyroidectomy should be performed only in patients who have previously been rendered euthyroid.

89
Goitre is the enlargement of the thyroid gland.

90
Hypothalamo-pituitary-adrenal axis

Cushing’s syndrome
Cushing’s syndrome – Increased circulating glucocorticoid

Cushing’s disease – Excess endogenous secretion of ACTH from a pituitary adenoma

Clinical feature

●Pigmentation

●Cushinoid appearance

●Weight gain

●Impaired glucose tolerance

●Hypokalaemia

●Hypertension

●Proximal muscle weakness

●Bruising

●Amenorrhoea/oligomenorrhoea

●Depression

91
Diagnosis

Need 2/3 of the following

 24hr urinary cortisol

 Low dose dexamethasone test
 Midnight plasma cortisol/ late night salivary cortisol

Low dose dexamethasone test

[1mg Dexamethasone at bedtime
(11pm)
Measure cortisol at 9am in the
morning]

Not suppressed
Suppressed Not suppressed Pseudocushing
Cushing's syndrome

Obese
No Cushing's
syndrome Alcohol
CKD
High ACTH Low ACTH

Pituitary CD
Cortisol secreting adrenal
Ectopic ACTH adenoma/ carcinoma
Exogenous cortisol

92
 High dose Dexamethasone test
[8mg single dose/ 2mg 6hrly for 48hrs
Dexamethasone]
CRH stimulating test

Not
Suppressed ↑ ACTH
suppressed Not altered
↑ Cortisol

Ectopic ACTH
Ectopic ACTH Pituitary CD
Pituitary CD
Adrenal tumours

Other investigations

 Pituitary MRI
 Adrenal CT
 CXR/ Chest CT

Management

 To control cortisol hypersecretion – Metyrapone (11 ß-hydroxilase4 blocker)

Ketoconazole
 Cushing’s disease – Trans sphenoidal removal of the tumour
External pituitary irradiation
Adrenalectomy

Addison’s disease
Destruction of entire adrenal cortex.

Therefore glucocorticoid, mineralocorticoid and sex steroid production are reduced.

Reduced cortisol levels lead to increase CRH and ACTH production.

Primary adrenal insufficiency shows female predominance.

Clinical features

 Pigmentation (new scars/palmer creases)  Postural hypotension

 Weight loss  Hypokalaemia

93
 Short Synacthen test
[250mcg of IM/IV Synacthen
Measure cortisol]

Absent or impaired Increase cortisol at

cortisol 30min

Iry Adrenal IIry Adrenal IIry Adrenal

insuficiency insufficiency insufficiency

Prolong exogenous glucocorticoids

Prolong ACTH/ CRH deficiency

Long Synacthen test

[250mcg of IM/IV Synacthen
8hrly for 48hrs]

Progresisve increase in
No change in plasma
plasma cortisol
cortisol
(>20mcg/day)

Iry Adrenal insufficiency IIry Adrenal insufficiency

94
 IIry Adrenal
insufficiency

Insulin induced Short Metyrapone

hypoglycaemia test

↓Cortisol
Increase CRH by ↓(-ve) feedback
hypothalamus
No rise in
↑ACTH
ACTH
↑ ACTH
No rise in ACTH or
cortisol ↑ Cortisol Normal pituitary
Anterior pituitary
disease (↑exogenous
Normal pituitary glucocorticoids)
Anterior pituitary (↑exogenous
disease glucocorticoids)

Other investigations

 Autoantibodies
 CXR + CT abdomen
 Serum electrolytes, serum calcium and serum creatinine
 Blood glucose

Management

 Hydrocortisone 15-30mg daily

 Fludrocortisone 50-300mcg daily (Not needed much as glucocorticoids also have mineralocorticoid

95
Congenital adrenal hyperplasia
Autosomal recessive disorder.

Deficiency of an enzyme in the cortisol synthesis.

Reduced negative feedback increases ACTH secretion, causing adrenal hyperplasia.

Therefore 17-hydroxyprogesterone, androstenedione and testosterone levels are increased, leading virilization and salt
wasting due impaired aldosterone synthesis.

Clinical features

 Ambiguous genitalia in females

 Adrenal failure (hypotension, hypoglycaemia, collapse and with salt losing state resulting in hypotension and
hyponatraemia)

Primary hyperaldosteronism
Increased mineralocorticoid secretion.

Leads to sodium and water retention, potassium loss.

Due to adrenal adenomas (Conn’s disease) or idiopathic causes.

Hypertensive patients with high chance of having this:

 Under 35yrs without a family history of hypertension

 With accelerated (malignant) hypertension
 With hypokalaemia
 Resistant to conventional antihypertensive therapy/ resistant hypertension
 With unusual symptoms (sweating attacks or weakness)

Clinical features

 Muscle weakness  Hypertension

 Nocturia  Hypokalaemia
 Tetany
Investigations

 Plasma aldosterone: renin ratio

 Serum electrolytes
 Adrenal CT/ MRI

Management

 Adrenal adenoma – surgical removal

 Adrenal hyperplasia – Spironolactone (aldosterone antagonist)
 Calcium channel blockers for hypertension

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Secondary hyperaldosteronism
When there is excess renin and hence angiotensin II

Causes – accelerated hypertension and renal artery stenosis

Phaeochromocytoma
Very rare tumours of sympathetic nervous system that arise in adrenal medulla.

Secretes catecholamines, noradrenalin, and adrenaline.

Some are associated with MEN 2, Von Hippel-Lindau’s syndrome and neurofibromatosis

Clinical features

 Anxiety and panic attacks

 Hypertension
 Tachycardia/ arrhythmias
 Bradycardia
 Orthostatic hypotension
 Headache
 Weight loss

Investigations

 Urinary catecholamines and metabolites

 Resting plasma metanephrines
 Plasma chromogranin A
 CT/MRI

Management

 Complete alpha and beta blockade –

Phenoxybenzamine
 Tumour removal

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Hypothalamo-pituitary-gonadal axis

98
99
100
Thirst axis
Thirst and water regulation are largely controlled by ADH which is secreted by hypothalamus.

 At normal ADH levels

Collecting ducts
Stimulate V2
ADH become permeable
receptors
to water

Reduces diuresis Water migration

Absorbs hypotonic
and retention of via aquaporin 2
luminal fluid
water channels

 At high ADH levels – vasoconstriction via V1 receptors in vascular tissue

Vasopressin secretion is suppressed - < 280mOsm/kg

Normal osmolality – 295mOsm/kg

Thirst is experienced – 298mOsm/kg

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Factures affecting ADH secretion

Increased by Increased osmolality

Hypovoaemia
Hypotension
Nausea
Hypothyroidism
Angiotensin III
Adrenaline
Cortis
Nicotin
Decreased by Decreased osmolality

Hypervolaemia

Hypertension

Ethanol

Alpha adrenergic stimulation

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Diabetes insipidus

Deficiency of ADH Compensatory

Excess excretion of
increase in thirst
or insensitivity to dilute urine
its action (polydipsia)

Daily urine output may reach as much as 10-15L.

ADH deficiency due

Cranial DI to hypothalamic
disease
DI
Renal tubules are insensitive to ADH
Nephrogenic DI (Abnormality in the Vasopressin-2
receptors or Aquaporin-2
receptors)

Causes for DI

Cranial DI Nephrogenic DI
• Familial isolated vasopressin • Familial
deficiency • Idiopathic
• Wolfram's syndrome • Renal tubular acidosis
• Idiopathic (Autoimune) • Hypokalaemia
• Tumours (Craniopharygioma, • Hypercalcaemia
glioma, germinoma, lymphoma • Drugs (Lithium, glibenclamida)
• Infections (TB, meningitis, • Sickel cell disease
cerebral abscess)
• Prolong polyuria
• Infiltrations (Sarcoidosis)
• Inflammatory
• Post surgical
• Vascular (Sheehan's, Aneurysm)
• Trauma

Biochemistry

 ↑ /High normal plasma osmolality (>300mOsm/kg)

 Low urine osmolality (<600mOsm/kg)
 ↑ /High normal plasma sodium
 High 24hr urine volume (>2L)

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 Water
deprivation test

•Fasting from 7.30am

or overnight
•Monitor serum and
urine smolalty, urine
volume and weight
hourly for 8hrs

•Serum osmolality •Serum osmolality

275-295mOsm/kg >300mOsm/kg
•Urine osmolality •Urine osmolality
>600mOsm/kg <600mOsm/kg

Normal response DI

Desmopressin 2mcg
IM

Urine osmoalality-no Urine osmolality rises

change by >50%
Nephrogenic DI Cranial DI

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Management

Cranial DI Nephrogenic DI

• Synthetic ADH (Desmopressin) • Thiazide diuretics for polyuria

IM/oral/intranasal

Other causes of polyuria and polydipsia

 Diabetes mellitus
 Hypokalaemia
 Hypercalcaemia

Primary polydipsia
A psychiatric disturbance characterized by excessive intake of water.

Plasma sodium and osmolality are reduced and urine produced is diluted.

Water deprivation test

Low plasma and urine osmolality at the begining

Urine osmolality increases gradually, but maximum concentration

ability may be impaired.

Prolong primary polydipsia may lead to ‘renal medullary washout’, with falling urine concentrating
ability of the kidney.

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SIADH
Inappropriate secretion of ADH leads to water retention and hyponatraemia.

• Small cell carcinoma of lung

• Prostate
• Thymus
Tumours • Pancreas
• Lymphomas
• Brain

• Pneumonia
Pulmonary • TB
lesions • Lung abscess

• Meningitis
• Head injuries
• SDH
CNS • Cerebral abscess
• SLE
• Vasculitis

• Alcohol withdrawal
Metabolic • Porphyria

• Chlorpropamide
• Carbamazepine
Drugs • Cyclophosphamide
• Phenothiazines

Clinical features

 Mild symptoms - <125mmol/L – confusion, nausea, irritability

 Serious symptoms - <115mmol/L – fits, coma

Investigations

 Hyponatraemia
 Euvolaemia
 Low plasma osmolality < urine osmolality (>100mOsm/kg)
 Urinary sodium >30mmol/L
 No hypokalaemia
 Normal renal, adrenal and thyroid function

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Management

 Correct the underlying cause

 Restrict fluid intake to 500-1000mL daily
 Frequent measurement of plasma osmolality, serum Na, and body weight
 Hypertonic saline – when plasma Na is <125mmol/L, for correction up to 125mmol/L
 Vasopressin V2 antagonist (Tolvaptan)
 Demeclocycline (If water restriction is poorly tolerated)

Calcium Metabolism

Serum calcium levels are mainly controlled by parathyroid hormone (PTH) and vitamin D.

PTH has several major actions, all serving to increase plasma calcium by:
• increasing osteoclastic resorption of bone (occurring rapidly)
• increasing intestinal absorption of calcium (a slow response)
• increasing synthesis of 1,25-dihydroxyvitamin D3
• increasing renal tubular reabsorption of calcium
• increasing excretion of phosphate

Hypercalcemia

Primary hyperparathyroidism is caused by single (>80%) parathyroid adenomas or by diffuse

hyperplasia of all the glands (15–20%).

Tertiary hyperparathyroidism is the development of apparently autonomous parathyroid hyperplasia

after longstanding secondary hyperparathyroidism, most often in renal failure.

Calcium levels are low or normal in secondary hyperparathyroidism.

The common primary tumours causing hypercalcemia are bronchus, breast, myeloma, oesophagus,
thyroid,prostate, lymphoma and renal cell carcinoma.

107
Clinical features

Investigations

Serum PTH,Renal functions,24-h urinary calcium levels,ALP can be done as investigations to confirm
the diagnosis and to find the cause.

Additionally;

•Protein electrophoresis/immunofixation: to exclude myeloma.

•Serum TSH: to exclude hyperthyroidism.
•9am cortisol and/or ACTH test: to exclude Addison’s disease.
•Serum ACE: helpful in the diagnosis of sarcoidosis.

Imaging with Radioisotope scans, CT, DEXA, Abdominal X-rays are also helpful to find the etiology.

108
Management of acute severe hypercalcemia

Management of primary hyperparathyroidism

High fluid intake should be maintained and replacement of vitamin D can be done.

New therapeutic agents that target the calcium-sensing receptors (e.g. cinacalcet) are of proven
value in parathyroid carcinoma and in dialysis patients and are used in primary hyperparathyroidism
where surgical intervention is contraindicated.

Surgical management can be used in symptomatic hypercalcemia, end organ disease.

Familial hypocalciuric hypercalcemia is an uncommon autosomal dominant, and usually

asymptomatic, condition demonstrates increased renal reabsorption of calcium despite
hypercalcaemia. PTH levels are normal or slightly raised and urinary calcium is low.

109
Hypocalcaemia

Clinical features

Hypoparathyroidism presents as neuromuscular irritability and neuropsychiatric manifestations.

Paraesthesiae, circumoral numbness, cramps, anxiety and tetany are followed by convulsions,
laryngeal stridor, dystonia and psychosis.

Two signs of hypocalcaemia are Chvostek’s sign (gentle tapping over the facial nerve causes
twitching of the ipsilateral facial muscles) and Trousseau’s sign (inflation of the sphygmomanometer
cuff above systolic pressure for 3 min induces tetanic spasm of the fingers and wrist).

Severe hypocalcaemia may cause papilloedema and, frequently, a prolonged QT interval on the ECG.

Management

In vitamin D deficiency, colecalciferol is the most appropriate treatment. In other cases, alpha-
hydroxylated derivatives of vitamin D are preferred for their shorter half-life, and especially in renal
disease, as the others require renal hydroxylation.

110
Diabetes mellitus

Diabetes mellitus is a complex metabolic disorder characterized by chronic hyperglycaemia due to

relative insulin deficiency, resistance or both.

Pathophysiology

 Insulin is the key hormone involved in the regulation of cellular energy supply and
macronutrient balance derived from food.
 It is a peptide hormone comprising two polypeptide chains and is synthesized in the β cells
of the pancreatic islets of Langerhans
 After secretion, insulin enters the portal circulation and is carried to the liver, about 50% of
secreted insulin is extracted and degraded in the liver; the remainder is broken down by the
kidneys.
 C-peptide is only partially extracted by the liver but is mainly degraded by the kidneys.
 Insulin receptor- It comprises a dimer with two α-subunits, which include the binding sites
for insulin, and two β-subunits, which traverse the cell membrane. When insulin binds to the
α-subunits, it induces a conformational change in the β-subunits, resulting in activation of
tyrosine kinase and initiation of a cascade response involving a host of other intracellular
substrates. The insulin-receptor complex is then internalized by the cell, insulin is degraded,
and the receptor is recycled to the cell surface.
 Glucose metabolism-
Blood glucose levels are tightly regulated in health and rarely stray outside the range of 3.5–
8.0 mmol/L (63–144 mg/dL).
 The principal organ of glucose homeostasis is the liver, which absorbs and stores glucose (as
glycogen) in the post-absorptive state and releases it into the circulation between meals to
match the rate of glucose utilization by peripheral tissues.
 Glucose transporters-
A family of specialized glucose-transporter (GLUT) proteins carry glucose through the
membrane into cells. The function of GLUT-1 to -3 is insulin-independent but insulin
stimulates glucose uptake into muscle and adipose tissue through GLUT-4. GLUT-4 is
normally present in the cytoplasm, but after insulin binds to its receptor, GLUT-4 moves to
the cell surface where it creates a pore for glucose entry.
 In the fasting state, insulin’s main action is to regulate glucose release by the liver, while in
the postprandial state, it additionally promotes glucose uptake by fat and muscle.
 ‘Counter-regulatory hormones’ that antagonize insulin action- glucagon(secreted from the
pancreatic α-cells), noradrenaline (norepinephrine), cortisol, growth hormone, are released.
 These counter-regulatory hormones increase hepatic glucose production and reduce its
utilization in fat and muscle for any given insulin concentration.

Classification of diabetes

Type 1 diabetes (beta cell destruction)

• Immune-mediated

• Idiopathic

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Type 2 diabetes

• Insulin resistance with inadequate insulin secretion

• Formerly non-insulin dependent diabetes

Other specific types of diabetes

Diabetes secondary to genetic defects

• Genetic defects of β-cell function

– MODY (maturity-onset diabetes of the young)

– Glucokinase mutations

– Hepatic nuclear factor mutations

– Neonatal diabetes

– Mitochondrial diabetes

• Genetic defects of insulin action

– Leprechaunism

– Type A insulin resistance

– Rabson–Mendenhall syndrome

– Lipoatrophic diabetes

Diabetes secondary to exocrine pancreatic disease

• Chronic pancreatitis

• Haemochromatosis

• Pancreatic surgery or trauma

• Cystic fibrosis

• Neoplasia

• Fibrocalculous pancreatopathy

Diabetes secondary to endocrine disease

• Acromegaly

• Cushing’s syndrome

• Phaeochromocytoma

• Glucagonoma

• Hyperthyroidism

• Somatostatinoma

• Aldosteronoma

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Diabetes secondary to drugs and chemicals

• Glucocorticoids

• Thiazide diuretics

• Antipsychotics

• β-adrenergic receptor blockers

Infections

• Congenital rubella

• Cytomegalovirus

• Mumps

Uncommon forms of immune-mediated diabetes

• Stiff man syndrome

• Anti-insulin receptor antibodies

Other genetic syndromes sometimes associated with diabetes:

• Down’s syndrome

• Klinefelter’s syndrome

• Turner’s syndrome

• Prader–Willi syndrome

• DIDMOAD (Wolfram’s) syndrome

• Friedreich’s ataxia

• Huntington’s chorea

• Laurence–Moon–Biedl syndrome

• Myotonic dystrophy

• Porphyria

Gestational diabetes

Type 1 DM
 Type 1 diabetes belongs to a family of immune-mediated organ-specific diseases, which
include autoimmune thyroid disease, coeliac disease, Addison’s disease and pernicious
anaemia.
 Characterized by selective autoimmune destruction of the insulin producing cells of a
genetically predisposed individual.
 Initially, autoantibodies directed against pancreatic islet constituents appear in the
circulation and often predate clinical onset by many years.

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  This is followed by a phase of asymptomatic loss of β cell secretory capacity; histologically,
this is characterized by a chronic inflammatory mononuclear cell infiltrate of T lymphocytes
and macrophages in the islets, known as insulitis.
 Some recovery of endogenous insulin secretion may occur over the first few months after
diagnosis and treatment initiation (the ‘honeymoon period’). During this time, the insulin
dose may need to be reduced or even stopped.
 Increased susceptibility to type 1 diabetes is inherited but the disease is not genetically
predetermined.
 Genetic susceptibility is polygenic but the greatest contribution comes from polymorphisms
in the HLA region.
 Environmental factors- maternal factors such as gestational infection and older age
,viral infections including enteroviruses such as Coxsackie, exposures to dietary constituents,
such as early introduction of cow’s milk and relative deficiency of vitamin D, environmental
toxins (e.g. alloxan, Vacor) , childhood obesity, psychological stress.

Type 2 DM

 Type 2 diabetes is a condition in which insulin deficiency relative to increased demand leads
to insulin hypersecretion by a depleted β-cell mass and progression towards absolute insulin
deficiency, requiring insulin therapy.
 Glucagon secretion is increased in type 2 diabetes, likely because of diminished intra-islet
insulin, and leads to increased hepatic glucose output.
 The insulin response to oral glucose is greater than the response to intravenous glucose, a
phenomenon known as the incretin effect.
 The effect is mediated by two hormones, glucagon like peptide-1 (GLP-1) and glucose-
dependent insulinotrophic polypeptide (GIP), which are released by the gastrointestinal tract
following eating. Their major action is to increase glucose-induced β-cell insulin secretion,
while suppressing glucagon secretion, but they also slow gastric emptying and induce
satiety.The incretin effect is impaired in type 2 diabetes.

Oral hypoglycemic agents

Biguanides: metformin

 The precise mechanism of action of metformin remains unclear but may involve the
activation of the enzyme adenosine monophosphate (AMP) kinase, which regulates
cellular energy metabolism.
 Metformin reduces the rate of gluconeogenesis, and hence hepatic glucose output,
and increases insulin sensitivity.
 It does not affect insulin secretion, does not induce hypoglycaemia and does not
predispose to weight gain.
 In addition to its effects on glucose, it may also suppress appetite and stabilize
weight.
 First-line pharmacological agent in all type 2 DM.
 Metformin has been used alongside insulin in people with type 1 diabetes but only
with limited efficacy.

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  Metformin treatment led to a reduction in cardiovascular events.
 Adverse effects- gastrointestinal side-effects such as anorexia, nausea, abdominal
discomfort and diarrhoea. The effects can be mitigated by starting at low dose and
gradually increasing until the desired therapeutic effect is achieved.
 Metformin is contraindicated in renal impairment, cardiac failure and hepatic failure
because of the risk of lactic acidosis.
 Metformin should not be started in someone whose estimated glomerular filtration
rate (eGFR) is less than 45 mL/min per 1.73m2 and should be stopped if the eGFR
falls below 30 mL/min per 1.73m2.
 Metformin must be stopped prior to intravascular administration of iodinated
contrast agent because of the risk of renal failure and subsequent lactic acidosis.
 Treatment can be restarted 48 hours after the test if there has been no
deterioration in renal function.
 Metformin should be stopped temporarily around surgery or during other
intercurrent illnesses that may affect lactate clearance.
 Metformin should be avoided in people with a history of alcohol misuse.
 Metformin reduces gastrointestinal vitamin B12 absorption, but only rarely causes
anaemia.

Sulphonylureas

 Sulphonylureas act on the β cell to induce insulin secretion.

 No effect in people with type 1 diabetes.
 Sulphonylureas bind to the sulphonylurea receptor on the β-cell membrane, which
closes ATP-sensitive potassium channels and blocks potassium efflux. The resulting
depolarization promotes calcium influx and stimulates insulin release.
 An alternative first-line agent where metformin is contraindicated or not tolerated.
 Weight gain, typically 1–4 kg, and hypoglycaemia are the most common side effects.
 The risk of hypoglycaemia is increased with longer acting sulphonylureas, excessive
alcohol intake, and older age and during intercurrent infection. Severe
sulphonylurea-induced hypoglycaemia should be managed in hospital for up to 48
hours with glucose support until the drug has cleared from the circulation.
 Sulphonylureas should be used with care in people with liver or renal disease.
 Ex:- Gliclazide, Glimepiride, Glibenclamide, Glipizide, Tolbutamide

Meglitinides or post-prandial insulin releasers

 Meglitinides are short-acting agents that promote insulin secretion in response to

meals.
 Mode of action- Like sulphonylureas, meglitinides act by closing the K+-ATP channel
in the β cells.
 They are rapidly metabolized and have a short duration of action of less than 3
hours.
 Meglitinides may be used to treat people with post-prandial hyperglycaemia with
normal fasting glucose levels.

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  They may be useful in older frail people where there is an imperative to avoid
hypoglycaemia. meglitinides are less effective than other drugs and their role in
diabetes management is not well established.
 Hypoglycaemia and weight gain are the most common adverse effects but these are
generally less severe than with sulphonylureas.

Thiazolidinediones or ‘glitazones’

 In many countries, pioglitazone is the only available thiazolidinedione.

 Thiazolidinediones reduce insulin resistance by interaction with peroxisome
proliferator-activated receptor-gamma (PPAR-γ).
 They reduce hepatic glucose production, an effect that is synergistic with that of
metformin, and also enhance peripheral glucose uptake.
 Like metformin, the glitazones potentiate the effect of endogenous or injected
insulin.
 Can be used as monotherapy or in combination with other antidiabetes drugs,
including insulin.
 Thiazolidinediones do not cause hypoglycaemia as monotherapy and pioglitazone
may specifically benefit people with non-alcoholic fatty liver disease,
 Thiazolidinediones may take up to 3 months to reach their maximal effect.
 The most common adverse effect is weight gain of 5–6 kg, but pioglitazone may
cause fluid retention precipitating heart failure. Mild anaemia and osteoporosis
resulting in peripheral bone fractures.

Dipeptidyl peptidase-4 inhibitors or ‘gliptins’

 DPP4 inhibitors enhance the incretin effect.

 These drugs inhibit the enzyme DPP4, which prevents the rapid inactivation of
glucagon-like peptide-1(GLP-1),which in turn increases insulin secretion and reduces
glucagon secretion.
 DPP-4 inhibitors are most effective in the early stages of type 2 diabetes, when
insulin secretion is relatively preserved.
 currently recommended for second-line use in combination with metformin or a
sulphonylurea.
 DPP-4 inhibitors do not promote weight gain, have a low risk of hypoglycaemia and
can be used safely in people with renal impairment.
 Adverse effects- Nausea,acute pancreatitis.
 DPP-4 inhibitors do not alter the incidence of myocardial infarction, but saxagliptin
may increase the risk of heart failure.

Sodium-glucose transporter 2 inhibitors (‘flozins’)

 In addition to their effects on blood glucose, they lower body weight, improve renal
dysfunction and reduce the risk of atherosclerotic cardiovascular events and heart
failure. It has a lower risk of hypoglycaemia.
 Mode of action- SGLT2 inhibitors lower the renal threshold for glucose,
consequently increasing urinary glucose excretion.
 SGLT2 inhibitors can be used as monotherapy but are used more typically in
combination with all other antidiabetes drugs.

116
  The glucose lowering effect is dependent on good renal function but the
renoprotective benefits are seen in people with lower eGFR.
 SGLT2 inhibitors are licensed as adjunctive therapy to insulin in type 1 diabetes.
 The most common adverse effects are genital candidiasis and dehydration.
 Rarer side effects include diabetic ketoacidosis, Fournier’s gangrene and lower limb
amputation.

Alpha-glucosidase inhibitors

 Alpha-glucosidase inhibitors, such as acarbose, are designer drugs that reduce

carbohydrate absorption after a meal.
 Mode of action- Alpha-glucosidase inhibitors prevent α-glucosidase, the last enzyme
involved in carbohydrate digestion, from breaking down disaccharides to
monosaccharides. This slows the absorption of glucose after a meal and lowers post-
prandial glucose.
 can be used as monotherapy or in combination with all other antidiabetes drugs
 have a limited efficacy
 The major side-effects are gastrointestinal and include flatulence, abdominal
distension and diarrhoea, as unabsorbed carbohydrate is fermented in the bowel.

Quick-release bromocriptine

 Abnormal circadian rhythm is associated with the development of insulin resistance,

obesity and diabetes.
 When administered at daybreak, quick-release bromocriptine appears to reset
hypothalamic dopamine circadian rhythms. The drug is well tolerated.

Colesevelam

 Colesevelam is a bile acid-binding resin that lowers cholesterol, and can reduce
blood glucose concentrations by an unknown gastrointestinal mechanism.

Non-insulin injectable therapies for type 2 diabetes

GLP-1 receptor agonists

 Act by enhancing the incretin effect.

 At present GLP-1 receptor agonists require injection but oral formulations are in
late development.
 Clinical trials have demonstrated that human GLP-1 analogues, but not exendin-
based GLP-1 receptor agonists, reduce the risk of myocardial infarction, stroke,
cardiovascular death and heart failure.
 GLP-1 receptor agonists enhance the incretin effect by activating the GLP-1 receptor.

117
  In addition to their effects on the pancreas to increase insulin secretion and
decrease glucagon, they also act on the hypothalamus to reduce appetite and food
intake leading to weight loss.
 Used in combination with other antidiabetes agents, as second-or third-line
therapies.
 The most common side-effects are gastrointestinal and include nausea and
vomiting, bloating and diarrhoea.
 Low risk of hypoglycaemia
 Avoid use in patients with history of acute pancreatitis.

Insulin

 Insulin is always indicated in people with type 1 diabetes and is often needed in those
with type 2 diabetes as the condition progresses.
 Philosophy of insulin therapy is to mimic the normal physiological secretion of insulin as
closely as possible. This involves the use of both long--acting insulin to replicate the basal
secretion of insulin and short--acting insulin to cover mealtimes

Short acting insulins

 Soluble human insulin (stable hexamers (six insulin molecules around a zinc core))
 absorbed slowly, reaching a peak 60–90 minutes after subcutaneous injection action tends
to persist after meals, predisposing to hypoglycaemia
 should be injected 20–30 minutes prior to a meal
 Short acting insulin analogues
 insulin lispro
 insulin aspart
 insulin glulisine
 Dissociate more rapidly following injection without altering the biological effect
 enter and disappear from the circulation more rapidly than soluble insulin
 Insulin analogues in people with type1 diabetes reduces total and nocturnal hypoglycaemic
episodes and improves glycaemic control as judged by postprandial glucose concentrations
and HbA1c with type 2 better control of HbA1c and postprandial glucose

Intermediate and longer acting insulins

 prolonged by the addition of zinc or protamine

 NPH (neutral protamine Hagedorn) or isophane insulin
 need to resuspend the insulin prior to injection and a peak action generally occurs in the
middle of the night

 Insulin glargine
 precipitates at subcutaneous pH
 longer and flatter duration of action

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  Insulin detemir and insulin degludec
 Long acting insulin analogues reduce hypoglycaemia for people with both type 1diabetes
and type 2 diabetes, particularly at night

 Most insulin is formulated as 100 units/mL but more concentrated forms are available, for
example insulin glargine is available as U300 (300 units/mL)

 Some people with diabetes experience severe insulin resistance and require massive insulin
doses. U500--strength insulin is available for these individuals

Insulin regimens

 The possible treatment options should be discussed with the individual to find the one
that is most suitable to their needs and lifestyle.

Basal bolus regimen

 Administration of both short and long--acting insulin.

 Long-acting insulin is injected 1–2 times per day to provide the background(basal) insulin to
keep the glucose concentration consistent during periods of fasting
 Short-acting insulin is given shortly before eating as a bolus to control glucose concentration
following a meal
 closely mimics normal insulin physiology
 More flexible than other regimens as each injection can be adjusted individually.
 treatment of choice for people with type 1
 Better for younger people with type 2 diabetes who have busy jobs
 main disadvantage of a basal-bolus regimen is the number of injections

Twice-daily mixed insulin regimen

 mixture of short and long-acting insulin is injected before breakfast and the evening meal
 Used more commonly for people with type 2 diabetes but may be used by people
with type 1 diabetes when it is not possible inject four times a day.

Basal only and basal-plus insulin regimens

 people with type 2 diabetes are able to produce insulin

 less intensive insulin regimen
 Basal long--acting insulin at night, together with other non--insulin treatments during the
day

Insulin administration – refer lecture notes.

119
Lipohypertrophy and lipoatrophy

 Fatty lumps, known as lipohypertrophy, may occur following the overuse of a single
injection site with any type of insulin
 immunoglobulin G immune complexes against the insulin can be formed that can
produce local atrophy of fat tissue (lipoatrophy)

Challenges of insulin therapy

 therapeutic index of insulin is low

 adjust insulin doses to maintaining blood glucose values between 4 mmol/L and 7 mmol/L
(70–126 mg/dL) before meals and between 4 mmol/L and 10 mmol/L (70–180 mg/dL)
after meals

Complications of diabetes
 microvascular complications that affect the capillaries and arterioles throughout the body
but particularly involve the eyes (retinopathy), kidneys (nephropathy) and nerve
(neuropathy)
 macrovascular increase the risk of myocardial infarction, stroke and peripheral vascular
disease

Microvascular complications

 specific to diabetes
 affect over 80% of individuals with diabetes
 Unusual in the first 10 years after the diagnosis of type 1diabetes but are found in 20–50%
of people with newly diagnosed type 2 diabetes
 Thickening of the capillary and arteriole basement membrane seen most people with dm
 organ damage occurs much less frequently
 with time vessels become progressively narrower and eventually become blocked ischaemia
and tissue dysfunction
 tissues damaged by hyperglycaemia are those that have high blood flow and cannot
downregulate glucose uptake in the presence of hyperglycaemia

Consequences of hyperglycaemia

 Formation of advanced glycation end products (AGE

 accumulate in proportion to hyperglycaemia and time
 HbA1c, which is used to diagnose diabetes and monitor treatment
 cause tissue injury and inflammation via stimulation of pro-inflammatory factors,
such as complement and cytokines
 Increased flux of glucose through the sorbitol–polyol pathway
 accumulation of sorbitol and fructose
 cause changes in vascular permeability, cell proliferation and capillary structure

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  Abnormal microvascular blood flow swamps the normal autoregulatory mechanisms that
limit tissue blood flow and the high flow rates damage the tissue

Diabetic retinopathy

 most commonly diagnosed diabetes--related complication

 prevalence increases with the duration of diabetes
 one--third of all people with diabetes
 10% of people with diabetes develop sight-threatening retinopathy,
 diabetic retinopathy is the most common cause of blindness in people of working age
 require laser photocoagulation to prevent or limit progression to proliferative retinopathy
 earliest changes non-proliferative or background retinopathy
 Damage to the wall of small vessels causes microaneurysms (small red dots)
 When vessel walls are breached, superficial (blot) haemorrhages occur
 Micro-infarcts within the retina due to occluded vessels cause cotton wool spots, spot is
swelling of the retinal nerve fibers because normal axoplasmic transport is disrupted leading
to the accumulation of axoplasmic debris. This debris is removed by macrophagesprevious
cotton wool spot (cytoid bodies)

 next stage pre-proliferative retinopathy

 further progression proliferative retinopathy

 Blockage of blood vessels leads to areas of capillary non-perfusion and ischaemia

 release of vascular growth factors such as VEGF cause neovascularization.

 other vessels whose walls are damaged and dilated, give the appearance of intraretinal
microvascular abnormalities (IRMAs) a feature of preproliferative retinopathy.

 these poorly supported new vessels can damage and cause small haemorrhages give rise to
pre-retinal haemorrhages (boat-shaped haemorrhages)

 vitreous haemorrhage may occur with sudden loss of vision

 collagen tissue grows gives rise to fibrotic bands may contract and further haemorrhage
and retinal detachment

 Maculopathy - Non-proliferative retinopathy may affect vision if it is situated within the

macular area

Management
 Prevention is the best way
 short-term deterioration of retinopathy may occur following rapid improvement in
glycaemic control and during pregnancy and by nephropathy

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  lipid-lowering drug, fenofibrate, has been shown to low the progression of retinopathy
including macular oedema. Smoking cessation is recommended
 Repeated injections of anti-VEGF drugs such as bevacizumab
 Laser photocoagulation therapy is used to treat the new vessels of proliferative retinopathy
 Although laser treatment prevents blindness, the main adverse effects result from the
destruction of retinal tissue. The visual field becomes permanently smaller and there
is reduced dark adaptation. Peripheral vision is sacrificed to maintain central vision.

Other ways in which diabetes can affect the eye

 Cataract
 Refractory defects
 External ocular palsies
 open--angle glaucoma
 Blindness

Diabetic nephropathy

 characterized by gradually increasing urinary albumin excretion and blood pressure as

the glomerular filtration rate falls insidiously towards end--stage renal disease
 15–25 years after the diagnosis of diabetes affects 25–35% of people
 increases the risk of cardiovascular risk and most people with nephropathy die from
cardiovascular disease before progressing to end--stage renal disease.
 earliest functional abnormality in the diabetic kidney is renal hypertrophy associated with
a raised glomerular filtration rate. As the kidney becomes damaged the afferent
arteriole becomes vasodilated to a greater extent than the efferent glomerular arteriole.
This increases the intraglomerular filtration pressure, further damaging the
glomerular capillaries
 mesangial cell hypertrophy
 increased secretion of extracellular mesangial matrix material
 eventually leads to glomerular sclerosis, both diffuse and nodular glomerulosclerosis
 Gradually increasing urinary albumin excretion is the hallmark of classical diabetic
nephropathy
 earliest evidence is microalbuminuria
 proteinuria may become so heavy as to induce a transient nephrotic syndrome, with
peripheral oedema and hypoalbuminaemia

Other features
 typically associated with a normochromic normocytic anaemia and raised erythrocyte
sedimentation rate, C--reactive protein
 Hypertension is common

Screening
 at least annually

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  for microalbuminuria which is albumin : creatinine ratio (ACR, tested on a midstream
first morning urine sample) is less than 2.5 mg/mmol in healthy men and less
than 3.5 mg/mmol in healthy women
 Once proteinuria is present other possible causes should be considered and excluded
 Clinical suspicion of a non-diabetic cause of nephropathy may be provoked by an atypical
history, the absence of diabetic retinopathy
 Plasma creatinine level and eGFR should be measured regularly

Management
 similar to that of other causes of chronic kidney disease
 time course can be markedly slowed by early aggressive antihypertensive therapy
 ACE inhibitors and angiotensin receptor blockers
 meticulous glycaemic control
 The target blood pressure <130/80 mmHg
 Renin–angiotensin system blockers used in people with normal blood pressure and
persistent microalbuminuria
 Oral antidiabetes agents, partially excreted via the kidney (e.g. glibenclamide and
metformin), should be avoided
 insulin clearance is reduced in advanced renal disease insulin dosage is usually reduced
 SGLT2 inhibitors slow the progression of diabetic nephropathy and preserve renal function
 end--stage renal disease
 Chronic ambulatory peritoneal dialysis may be preferable to haemodialysis.
 The failure rate of renal transplants is somewhat higher than in people without diabetes.

Diabetic neuropathy

 Diabetes can damage peripheral nervous tissue in several ways

 occlusion of the vasa nervorum likely in isolated mononeuropathies
 diffuse symmetrical nature implies a metabolic cause
 hyperglycaemia → increased formation and accumulation of sorbitol and fructose in
Schwann cells → disruption of function and structure
 Eariest functional change is delayed nerve conduction velocity
 Earliest histological change is segmental demyelination
 a later stage, irreversible axonal degeneration occur

Symmetrical distal polyneuropathy

 Often unrecognized by the person in early stages.

 Early clinical signs are loss of vibration sense, pain sensation (deep before superficial) and
temperature sensation in the feet
 later stages, feeling of ‘walking on cotton wool’ and lose of balance when washing the face
or walking in the dark owing to impaired proprioception
 Early involvement of the hands is less common
 Involvement of motor nerves to the small muscles of the feet gives interosseous wasting.

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  Unbalanced traction by the long flexor muscles leads to a characteristic shape of the foot,
with a high arch and clawing of the toes, which causes abnormal distribution of pressure on
walking, resulting in callus formation under the first metatarsal head or on the tips of
the toes
 Hands - small-muscle wasting, sensory changes, these signs and symptoms must be
differentiated from carpal tunnel syndrome, which occurs with increased frequency in
diabetes.

Acute painful neuropathy

 A diffuse, painful neuropathy is less common - burning or crawling pains in the feet, shins
and anterior thighs
 typically worse at night and pressure from bedclothes may be intolerable
 may present at diagnosis or after sudden improvement in glycaemic control
 usually remits spontaneously after 3–12 months if good glycaemic control is
maintained sometimes resistant to almost all forms of therapy
 muscle wasting is not a feature and objective signs can be minimal
 important to explore non-diabetic causes
 Duloxetine, tricyclics, gabapentin or pregabalin (NICE recommends these as first-line
therapies), mexiletine, valproate and carbamazepine all reduce the perception of
neurotic pain but usually not as much as patients hope for
 Trans epidermal nerve stimulation (TENS) benefits some people

Mononeuritis and mononeuritis multiplex (multiple mononeuropathy)

 Onset is abrupt and sometimes painful. Radiculopathy (i.e. involvement of a spinal root) may
also occur.
 Isolated palsies external eye muscles, especially the third and sixth nerves, are more
common in diabetes
 third nerve lesions characteristic feature painless and the pupillary reflexes are retained
 Full spontaneous recovery over 3–6 months

Diabetic amyotrophy

 usually seen in older men

 Presentation is with painful wasting, usually asymmetrical, of the quadriceps muscles. may
be very marked and knee reflexes are diminished or absent.
 Affected area is often extremely tender.
 Extensor plantar responses sometimes develop and cerebrospinal fluid (CSF) protein
content is elevated.
 Associated with periods of more severe hyperglycaemia and may be present at diagnosis.
 Often resolves over time with improved glycaemic control.

Autonomic neuropathy

 Symptomatic autonomic neuropathy is rare.

 It affects both the sympathetic and parasympathetic nervous systems
 Can cause disabling postural hypotension
 Vagal neuropathy results in tachycardia at rest and loss of sinus arrhythmia.
 loss of sympathetic tone to peripheral arterioles Postural hypotension

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  warm foot with a bounding pulse
 Vagal damage gastroparesis, leading to intractable vomiting
 Include dysphagia, dyspepsia, abdominal pain, constipation, diarrhoea and faecal
incontinence.
 Autonomic diarrhoea characteristically occurs at night, accompanied by urgency and
incontinence
 Bladder incomplete emptying and stasis atonic, painless, distended bladder. Tx - intermittent
self-catheterization, permanent catheterization if that fails, and prophylactic antibiotic
therapy
 Sexual dysfunction
 common in both men and women
 first manifestation is incomplete erection
 which may, in time, progress to total failure retrograde ejaculation
 Tx - Phosphodiesterase type 5 inhibitors (sildenafil, tadalafil, vardenafil, avanafil),
which enhance the effects of nitric oxide on smooth muscle and increase penile
blood flow

The diabetic foot

 50% of older people with type 2 diabetes have risk factors for foot problems and 10–15% of
people with diabetes develop foot ulcers
 most common cause of non-traumatic lower limb amputation
 could be delayed or prevented by more effective self--management education and medical
supervision
 Ischaemia, due to pvd neuropathy and infection produce tissue necrosis and ulceration
 Ischaemia compromises the ability to heal after minor trauma or infection.
 Peripheral neuropathy means less able to perceive trauma and may continue to walk on a
wounded foot thereby worsening the injury.
 Autonomic neuropathy reduces sweating and alters blood flow resulting in dry skin that is
prone to crack and fissure.

Charcot neuroarthropathy

 complication of severe neuropathy occurs in a well--perfused foot and can be divided into
three phases
 acute onset
 bony destruction
 radiological consolidation and stabilization
 present with an acutely swollen hot foot and about a third have pain.
 may be difficult to differentiate from cellulitis; if in doubt, both conditions should be treated.
 Acute gout and deep vein thrombosis may also appear as Charcot arthropathy.
 If treatment is delayed foot can become deformed as bone is destroyed, often very rapidly
over a few weeks.
 After 6–12 months destructive process stabilizes.
 Rehabilitation is always necessary after a long period in a cast and reconstructive surgery
may be needed.
 The aim of treatment is to prevent or minimize bony destruction and deformity.

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  Any resulting deformity can alter the pressure distribution across the foot and predisposes
the foot to future ulceration.
 Immobilization in a non-weight bearing cast is the treatment of choice and should be
continued until the swelling and temperature in the foot has resolved.

 Management
 Key to managing is prevention.
 Learning about the principles of foot care is essential

Foot ulceration

 Ensure that the foot is non--weight-bearing.

 special shoes and insoles to move pressure away from critical sites
 Long-term to protect the feet and prevent abnormal pressure repeating damage to a healed
area.
 Neuropathic feet sharp surgical debridement is necessary to prevent callus distorting the
local wound architecture

Ischaemia

 confirmed by femoral angiography

 May be amenable to bypass surgery or angioplasty.

Infection

 Early broad--spectrum antibiotics with therapy adjusted in the light of culture results.
 The organism grown from the skin surface may not be the organism causing deeper
infection.
 Collections of pus are drained and excision of infected bone may be needed if osteomyelitis
develops and does not respond to appropriate antibiotic therapy.
 Regular X--rays of the foot are needed to check on progress.

Multidisciplinary diabetic foot team

 involving diabetologists working with podiatrists,

 orthopaedic and vascular surgeons,
 specialist nurses,
 orthotists
 other healthcare professionals

Microvascular complications

Atherosclerotic vascular disease

 Myocardial infarction, stroke, peripheral vascular disease and cardiovascular death are
increased two or threefold compared with the background population

 Management of atherosclerotic cardiovascular risk

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  involves the aggressive and systematic management of each of the predisposing factors
 Early tight glycaemic control reduces the long-term risk of cardiovascular disease.
 Type 2 diabetes with established cardiovascular disease use of SGLT2 inhibitors and GLP--1
receptor agonists is recommended because of their protective effect.
 Anti-hypertensive treatment produces a marked reduction in adverse cardiovascular
outcomes as well as microvascular events. Most will need combination drug therapy. ACE
inhibitors or angiotensin receptor blockers may confer additional benefit. Produces a 25–
35% lowering of the risk of heart attack, stroke, overt nephropathy or cardiovascular death.
 Angiotensin II receptor antagonists are sometimes preferred initially and are also used for
those intolerant to ACE inhibitors.
 Statins are recommended for those with diabetes over the age of 40 years or after a 10-
-year history of diabetes if microvascular complications are present
 Other lipid lowering agents, such as ezetimibe or PCSK9 inhibitors, are indicated if statins
are not tolerated or do not bring the cholesterol to target.
 Smoking cessation is important and help should be offered to those wishing to quit.
 Low-dose aspirin reduces macrovascular risk but is associated with a morbidity and
mortality from bleeding

Heart failure

 more common than atherosclerotic cardiovascular disease in people with diabetes

 both heart failure with preserved ejection volume and heart failure with reduced ejection
volume occur more frequently.
 The prognosis after the development of heart failure is poor
 The prevalence of undiagnosed heart failure is higher in those with increasing age, with
obesity, hypertension dyspnoea or fatigue and in women.
 The diagnosis and management of heart failure is similar to the general population but it is
important to consider the effects of diabetes medications on the heart failure.
 Pioglitazone and saxagliptin, a DPP4 inhibitor, increased the risk of heart failure
 GLP-1 receptor agonists have no effect on heart failure while SGLT2 inhibitors reduce the
risk.

Other complications of diabetes

Non--alcoholic liver disease and other gastrointestinal manifestations of diabetes

 (NAFLD) is characterized by intrahepatic fat accumulation with varying degrees of hepatic

inflammation and fibrosis.
 Over a third of people with NAFLD have diabetes
 NAFLD is an independent predictor of the development of diabetes and cardiovascular
disease.
 Associated with central obesity and insulin resistance

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Management

 Weight loss and exercise.

 Pioglitazone may also reduce intrahepatic fat.

Malabsorption secondary to gastrointestinal dysmotility malabsorption through chronic exocrine

pancreatic insufficiency.

 Treatment
 Pancreatic enzymes.

People with type 1 diabetes have a higher prevalence of coeliac disease.

Infections

 people with well-controlled diabetes are not more prone to infection,

 hyperglycaemia leads to more frequent infection through multiple disturbances in innate
immunity; by contrast, humoral immunity appears relatively unaffected.
 Microvascular disease may further impede the immune system contributing to the severity
of certain infections, including malignant otitis externa, emphysematous pyelonephritis and
necrotizing fasciitis.
 Some microorganisms, such as Klebsiella serotypes and Burkholderia pseudomallei, are more
virulent in hyperglycaemic environments.
 Urinary tract infections and asymptomatic bacteriuria are more common in people with
diabetes, with autonomic neuropathy a common and important underlying factor.
 Mycotic genital infections are more common, particularly in women.
 Skin and soft tissue infections are more common.
 The risk of tuberculosis is increased in people with diabetes.
 Certain viral infections, such as hepatitis C, and treatment for HIV/AIDS increase the
risk of diabetes.

Psychosocial implications of diabetes

 Psychological problems associated with diagnosis

 Diabetes-related distress
 Fear of hypoglycaemia
 Depression
 Eating disorders
 Consequences of psychological and psychiatric disorders of diabetes

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4. Haematology

Anaemia

Hypochromic microcytic anaemia

1. Iron deficiency anaemia- (Usual mcqs- clinical features and investigations given and we have to
identify it as IDA. Mx usually has not been asked.)
Hepcidin regulates iron absorption. High hepcidin (infections, inflammation) reduce absorption and
vice versa.
Blood picture- Anisocytosis (size variation), poikilocytosis (Shape variation)
Mx- find the cause. Treat with iron supplements. (Hb will increase by 10g/L per week) Usually given
orally. Given for at least 6 months to replenish the iron stores. Parenteral iron used if intolerant to
oral iron, malabsorption syndromes.

2. Anaemia of chronic disease (past mcqs are similar in nature to IDA mcqs)
Seen in IBD, Connective tissue diseases, inflammatory arthritides, cancers etc. High hepcidin levels
seen. Poor iron delivery to bone marrow occurs. (Hepcidin level can be used to identify but routinely
not available) Refer the above table for iron study parameters. Ferritin is normal or high due to
inflammation. In bone marrow study iron is absent in erythroblasts. (Blood picture- refer to the
specific shapes/ names of RBC in Shyamali madam’s note.) MCV normal or low in long standing
ACD.)
Mx- patients do not respond to oral iron. Tx the underlying disorder.
3. Sideroblastic anaemia
Due to ineffective haem synthesis. Can be inherited or acquired. (Acquired causes-
myeloproliferative disorders, myeloid leukaemia, drugs, lead toxicity, rheumatoid arthritis etc.)
In bone marrow studies excess iron and ring sideroblasts are present. (Iron accumulates in
mitochondria forming rings around the nuclei of erythroblasts. It is diagnostic of S. anaemia)
Sideroblasts are detected by Perls’ reaction. Blood picture is often dimorphic. (Read the list of
causes of dimorphic blood picture in Madam's note.)
Mx- if acquired tx the cause. May respond to pyridoxine.

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Normocytic anaemia
Seen in anaemia of chronic disease, some haematological conditions (some hemolytic anaemias,
aplastic anaemia), and acute blood loss.

Macrocytic anaemia (a common mcq topic – asked very commonly in the past regarding causes of
megaloblastic and non- megaloblastic anaemias)
1. Megaloblastic anaemia
Occur due to folate or B12 deficiency.
B12 is present only in animal products, not in plants. Folate is present in plants. (Foliage).
Commonest cause of B12 deficiency is pernicious anaemia.
Clinical features
Lemon yellow jaundice, Glossitis, angular stomatitis. Neurological features of B12 deficiency (past
MCQ)- polyneuropathy, Subacute combined degeneration of spinal cord (Dorsal column and later
lateral columns involved)
Ix
MCV is >96 fL. Blood picture shows oval macrocytes with hyper segmented neutrophils. LDH is
typically high. Bone marrow - Megaloblastic erythropoiesis. LDH and serum bilirubin may be
elevated due to ineffective erythropoiesis. Serum B12 low.

Mx
IM Hydroxocobalamin (B12)
Folate deficiency- Commonest is poor intake.
Body Folate reserve is adequate for 4 months. NO NEUROLOGICAL FEATURES in folate deficiency.
(Ix-see b12 deficiency ix).
Mx- folic acid

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2. normoblastic (non-megaloblastic) macrocytic anaemia

No hyper segmented neutrophils. Normoblastic bone marrow.

Causes- A common MCQ. See the image.

Aplastic Anaemia (Anaemia due to bone marrow failure)

Pancytopenia with bone marrow hypocellularity. (Aplasia)
Features- Anaemia, Bleeding, infections
Ix- pancytopenia, absent reticulocytes, hypocellular marrow (exclude other causes of pancytopenia)
Mx- tx the cause. Prevent/tx infections. (If infection suspected in a neutropenic patient- immediate
broad-spectrum antibiotics.) Haemopoietic stem cell transplants. (Allogeneic bone marrow
transplants) Immunosuppressive therapy- Anti thymocyte globulin, ciclosporin.

Haemolytic anaemia

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Features- Bone marrow erythroid hyperplasia (compensation), reticulocytosis, polychromasia in
blood picture, gallstones
1. Extravascular haemolysis- by macrophages in reticuloendothelial system (mainly spleen) Causes-
hereditary spherocytosis, pyruvate kinase deficiency, Warm autoimmune haemolytic anaemia
(remember as HS,PK,Warm AIHA)
2. Intravascular haemolysis- within circulation. Perls’ test positive (haemosiderin) Schumm test
positive. (methaemalbumin) Very low or absent haptoglobin.
Hereditary spherocytosis
A red cell membrane defect (spectrin deficiency). Usually, autosomal dominant. (Also, AR and de
novo mutations.) RBC become spherocytes and they get haemolysed while travelling through the
spleen.
Clinical features- May have jaundice at birth but may present years later. Gallstones, splenomegaly
Ix - Osmotic fragility test, evidence of haemolysis- high serum bilirubin & urinary urobilinogen,
Direct antibody test (Coombs’s test) negative.> to exclude autoimmune haemolytic anaemia.
Mx- most pts do not need specific tx. Splenectomy if abdominal discomfort or symptomatic
anaemia.

Thalassemia
Impaired globin pdn  precipitation of excess globin  ineffective erythropoiesis and haemolysis
Beta thalassemia clinically – carrier state (heterozygous) ,non Transfusion dependent Thalassemia(
coexistence of alpha thalassemia or alpha chains mopped up by gamma chains) and TDT
(homozygous or compound heterozygous)
Beta thalassemia is mainly of point mutations and alpha is mainly of gene deletions
HPLC for diagnosis.
Beta thalassemia- iron overload, splenomegaly, infection, leg ulcers, gall stones

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- Classical thal.facies ; on x-ray -> ‘hair on end’ appearance , expanded marrow with thin cortex in
hand
Mx- bld transfusion, folic acid – long term, splenectomy, mx of iron overload, marrow
transplantation and screening family members and counselling.
Gene for alpha globin chains is on chromosome 16.

Sickle cell Hb-

Homozygous- SC anemia(HbSS); heterozygous- SC trait(HbAS)
Clinical features- vaso- occlusive crisis, pulmonary hypertension, acute chest syndrome, anemia (
splenic sequestration and bone marrow aplasia) and other long term problems ( growth, chronic
bone infarcts, infections, leg ulcers, cardiac problems)
Hb electrophoresis needed to confirm diagnosis.
Mx- avoid or treat ppt factors, mx of acute painful crisis ( morphine, other adjuvant analgesia,
laxatives, antipyretics, antiemetics, anxiolytic), anemia ( transfusion, hydroxycarbamide , stem cell
transplantation), counselling.
G6PD deficiency
Lack of NADPH to reduce glutathione; X linked recessive
Fava beans, Drugs (aspirin, antimalarials, sulphonamides, nitrofurantoin, quinolones, dapsone, and
vit-K), infection and acute illness precipitate haemolysis.
Blood picture during attack- bite cells, blister cells, Heinz bodies, reticulocytosis.
Mx – treat cause, may need transfusion ,splenectomy not usually helpful
Autoimmune haemolytic anaemia
AIHA Warm (65%) Cold (30%)
Temp. 37’c Less than 37 (4’c)
Ab IgG IgM
D.Coombs test Str.positive Positive
2ry causes Rheumatic dis (SLE) Infection(mycoplasma, CMV, EBV),
CLL , Lymphoma(Hodgkin), lymphoma, PCH
carcinoma, Drugs

Haemostatic Disorders and coagulation disorders

Inherited Coagulation disorders

1. Haemophilia

a. A -Lack of factor VIII. X linked recessive. Clinically present depending on the

severity, joint bleeding, severe bleeding after injury, and occasional spontaneous
bleeds. Good prognosis. Die of cancer or heart attacks. Mild cases can be treated

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 with vasopressin. Severe cases treated with IV factor VIII concentrates, twice daily 3
times a week. Can develop inhibitors.

b. B- Factor IX deficiency. Same as above but less common. Treated with factor IX
concentrates but half-life is longer can give prophylactic doses.

2. Von Willebrand’s disease

Deficiency of VWF impaired platelet adhesion and factor VIII deficiency. Autosomal
dominant. Bleeding from minor trauma or surgery, epistaxis, menorrhagia, and mucosal
bleeding. Mx with desmopressin and rarely cryoprecipitate.

Acquired Coagulation disorders

1. Vitamin K deficiency –

Wanted for gamma-carboxylation of Factor 2,7,9,10. Could be due to low storage,

malabsorption of vit K, and oral anticoagulants. IV vit K 10mg given to adults with minor
bleeds. Given to new-borns.

2. Liver disease

Multifactorial such as low vit k, reduced synthesis of clotting factors, low PLT and functional
abnormalities, and DIC in acute liver failure.

3. DIC

It’s a consumption coagulopathy. Causes are malignant dx, septicaemia, haemolytic

transfusion reactions, amniotic fluid embolism, preeclampsia, placental abruption, trauma,
burns, liver dx, and snake bite. APTT, PT, and BT prolonged, high FDP, D dimers.

Mx by treating the underlying cause, transfusion of PLT, FFP, Cryo, RBC concentrates.
Heparin can be given but not tranexamic acid.

4. Massive Transfusion

5. Inhibitors of coagulation

a. In SLE like conditions, by Factor VIII autoantibodies in elderly pts with malignant
dx.

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Disorders of Platelet
Thrombocytopenia

There are so many causes so categorize and remember a few.

· Impaired production- Bone marrow failure, myeloma, myelofibrosis,

aplastic anemia

· Increased destruction or consumption- ITP, CLL, SLE, DIC, TTP

· Sequestration – hypersplenism, splenomegaly

· Dilutional – massive transfusion

Platelet function disorders

The count is normal but the function is impaired seen by increased Bleeding time. There are
inherited and acquired causes, remember acquired cases like Myeloproliferative Dx, Renal
and liver dx, and Drug-induced. PLT transfusion only if the bleeding risk is very high.

Thrombocytosis

PLT is more than 400 x 109. Could be due to Splenectomy, malignancy, IBD, RA, Fe deficiency,
myeloproliferative, or major surgery. Can increase the risk of thrombosis, so prophylactic
low dose aspirin is given in certain dx only.

Leukaemia
Aetiology – Radiation, Chemicals, Genetic, Viruses-HTLV1

Leukaemia

Myeloid Lymphoid

Acute AML ALL

Common in elderly, Rx with Common in childhood, very good prognosis in

induction chemotherapy then bone childhood dx, remission induction chemo and
marrow transplant, then consolidation chemo, allogenic transplant
in selected pts,

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Clinical Both myeloid and lymphoid show similar fx such as
fx
Marrow failure-Anaemic symptoms, recurrent infections, bleeding manifestations

High WBC-hypoxia, headache, low GCS, visual problems

Tissue infiltration- bone pain, hepatosplenomegaly, LNE, cranial nerve palsy,

Substance release- gout, AKI

Chronic CML CLL

Adult disease, Philadelphia Elderly disease, treated with biologics,

chromosome is present, slow
progression,

Clinical May be symptomless or anaemic Asymptomatic, recurrent infection, anaemia,

fx symptoms, splenomegaly, LOW, generalized or local LNE , Splenomegaly,
fever with night sweats, headache,
pallor.

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Lymphoma
Always diagnosis is confirmed by biopsy results.

Hodgkin Lymphoma (HL) Non-Hodgkin Lymphoma (NHL)

Common in males, EBV has a role in Common genetic polymorphism is present, pt s with
pathogenesis. immunosuppression has a increased risk, some bacteria and
viruses were also shown to increase risk such as HTLV1,
Classic HL has Reed Stenberg cell. EBV, HIV, H.pylori, Chlamydia psittaci.

Commonly present with rubbery, B cell Lymphomas

painless lymphadenopathy,
hepatosplenomegaly, B symptoms.
Best Ix is PET CT,
Mx with Chemotherapy (ABVD)
· Diffuse large B cell lymphoma- commonest adult
lymphoma,
· Follicular Lymphoma-second commonest NHL, rare in
children

· Burkitt’s lymphoma- rapidly proliferating, most

common childhood malignancy, strong association with
EBV, and immunodeficiency.

· There are so many types feel free to read

T cell Lymphomas

· Two types- Peripheral T cell Lymphoma and

angioimmunoblastic T cell Lymphoma

Multiple Myeloma

Myeloma is a disease of the elderly. For features remember ‘CRAB’. C- Hypercalcaemia, R- renal
injury, A- anaemia, B- Bone destruction.

Ix- FBC- Hb, WBC, PLT - normal or increased

ESR - high
Blood picture - rouleaux formation
S. Ca - normal or increased
ALP - usually normal
Total protein- normal or increased
S.protein electrophoresis - characteristically shows monoclonal band & immuneparesis
Skeletal survey - characteristic lytic lesions specially in the skull

Mx - Supportive care & chemotherapy

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Life threatening complications in MM (hv asked in SBA)
 Renal impairment - often due to hypercalcaemia - requires urgent attention and nephro
referral
 Hypercalcaemia - Rx by rehydration and bisphosphonates
 Spinal cord compression - dexamethasone followed by radiotherapy
 Hyperviscosity - plasmaparesis

Myeloproliferative disorders

01) Polycythaemia rubra Vera

02) Essential thrombocytosis
03) Myelofibrosis

Polycythaemia
Can be divided as primary & secondary. Secondary polycythaemia can be divided into Relative
(dehydration, burns) & True. True secondary polycythaemia can be further divided into, due to
appropriate increase in EPO (due to hypoxia) & inappropriate increase in EPO (due to EPO secreting
tumours)

Rx- Venesection

Blood transfusion

 Procedure of administrating blood or a blood component

o Make sure the ticket belongs to the right patient

 name, age, address

 brief history
 check whether blood transfusion was ordered and who decided on it
o Check whether the information on the correct blue chit issued from the blood bank,
compatible with the information on the BHT
o Check whether the information in the blood unit are compatible with the
information in the blue chit.
o Examine the blood unit for discolouration, leaks, air bubbles, clumps, clots, or
haemolysis.
o Before administration, describe the procedure to the patient.
o Let the patient empty the bladder and bowels before starting, if needed.

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 o Assess the vital functions of the patient.
o Start the transfusion
o Take the correct BHT and record the time of transfusion and instructions to nursing
staff on monitoring of the patient and what to do if a reaction occur.
o Medical officer better to remain in the ward for at least 30 minutes after the
transfusion has started, as transfusion reactions can occur.

 Complications of blood transfusions

o Immunological (Alloimmunization and incompatibility)
 Red cells
 immediate haemolytic transfusion reactions
 delayed haemolytic transfusion reactions
 White cells
 non-haemolytic (febrile) transfusion reactions
 transfusion related acute lung injury
 transfusion associated graft versus host disease
 Platelets
 post transfusion purpura
 Plasma proteins
 urticaria and anaphylaxis
 immunosuppression
o Non-immunological
 Transmission of infections
 viral →HAV, HBV, HCV, HEV, HIV, CMV, dengue, zika
 bacterial
 parasitic →Malaria
 prions
 Transfusion-associated circulatory overload
 Iron overload →due to multiple transfusions

Anticoagulants
 Indirect thrombin inhibitors
o unfractionated heparin →action reversed by protamine sulphate
o LMWH (enoxaparin)
 Direct thrombin inhibitors
 Vitamin K antagonists
o Warfarin

 Direct factor Xa inhibitors (newer agents)

o apixaban
o Rivaroxaban

 INR values when on warfarin

o 2.5 (2.0-3.0) →DVT, cancer, APLS, atrial fibrillation or flutter, mitral stenosis,
mechanical valve at the aortic position
o 3.0 (2.5-3.5) →mechanical valve in the mitral position

139
 What to do when INR value is over the targets

o high but <4.5 →decrease or hold the warfarin dose, increase the frequency of
monitoring and start at a lower dose when INR is within the therapeutic range (can
continue the same dose if elevated <0.5 over the threshold) / NO vitamin K given
o 4.5-10 →decrease or hold the warfarin dose, increase the frequency of monitoring
and start at a lower dose when INR is within the therapeutic range / NO vitamin K
given
o 10 →hold warfarin and give oral vitamin K at 2.5-5mg doses and start warfarin at a
lower dose when the INR is within the therapeutic range
o To quickly reverse the action →can use prothrombin factor concentrates, FFP or IV
vitamin K

 Advantages of LMWH over unfractionated heparin

o routine monitoring not required
o as effective as unfractionated heparin
o less frequent dosing
o predictable and dose dependant plasma level

o but unfractionated heparin action can be reversed quickly by protamine sulphate

and it provides immediate action when given the drug

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5. Rheumatology and Bone Diseases

Shoulder Pain

Common in diabetics

DDx

 Rotator cuff (supraspinatus) tendinosis

Common
Radiates to upper arm,
‘Painful arc syndrome’.

 Adhesive capsulitis (true ‘frozen’ shoulder)

After rotator cuff injury, hemiplegia, breast sx, MI

Pain – initially, severe —> reducing range of movements —> no movements (frozen
shoulder) + little pain

 Torn rotator cuff

In trauma, old age & in RA

Abduction is affected

 Calcific tendinosis and bursitis

Not always symptomatic

Calcium pyrophosphate deposition on tendons
Visible on X-ray
Can mimic gout, pseudo gout and septic arthritis

 Cervical nerve root pain

Pins and needles sensation / neuro signs in the arm

 Muscular neck pain (shoulder girdle pain)

Does not radiate to the upper arm

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Osteoarthritis

 This is due to damage to articular cartilage.

 Pathogenesis – loss of cartilage expose, the underlying bone to increased stress leading to
micro fractures and cysts causing abnormal sclerotic subchondral bone (osteophytes)

 Factors predisposing to OA – obesity, gender(female), hypermobility,familial tendency,

osteoporosis, trauma, congenital joint dysplasia, occupation, sport(repetitive use and injury),
congenital dislocation of hip, Perthes’ dx etc.

 Clinical features – Symptoms – joint pain with the movement or weight bearing, short lived
morning joint stiffness, functional limitation

 Signs – crepitus, restricted movements, bony enlargement, joint effusion and variable levels
of inflammation, bony instability and muscle wasting

Clinical subsets
1. Localized OA

a) Nodal OA – common in females around menopause. Usually in hands. DIP > PIP
involvement. DIP – Heberden’s nodes, PIP – Bouchard’s nodes.

b) Hip OA – predominantly affecting the femoral head and acetabulum

c) Knee OA – more commonly in women, strong association with obesity and

generally bilateral.

2. Primary generalized OA

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 a) Erosive OA

b) Crystal associated OA

 Ix
o blood tests – lack specificity (ESR-N/L, RF- negative, CRP may be slightly raised)

o X-ray – features (cartilage loss) only in advanced dx

o MRI – early cartilage damages and osteochondral lesions
o Arthroscopy – early fissuring and surface erosions of cartilage

 Mx – Tx the symptoms and disability and not the radiological appearances

Physical measures – weight reduction, exercise for strength and stability,
hydrotherapy, TENS, acupuncture, thermotherapy
Medication – topical/oral NSAIDS, Intra articular corticosteroids
(No proven agents that halts or reverse OA)
Surgery – replacement arthroplasty (reduce pain, improve function, improve QoL),
re-alignment osteotomy, excision arthroplasty

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Rheumatoid Arthritis

Introduction and Epidemiology

 RA is a chronic inflammatory rheumatic disease

 chronic symmetrical polyarthritis with systemic inflammation.
 female preponderance of 3: 1
 presents from early childhood (when it is rare) to late old age
 most common age of onset is between 30 and 50 years

Pathology

 RA is primarily a synovial disease

 In RA, the synovium becomes greatly thickened, causing ‘boggy’ swelling around joints and
tendons, with proliferation of the synovium into folds and fronds, and infiltration by a
variety of inflammatory cells, including polymorphs

Risk Factors

 increased incidence in first--degree relatives

 strong association between susceptibility to RA and certain human leucocyte antigen (HLA)
specially HLA-DR4
 Environmental risks
o Smoking
o Alterations in the microbiome
 Autoantibodies
o Rheumatoid factor (RF)
o ACPA: More specific to RA and More Sensitive to RA
 ACPAs are usually present with RF in RA
 RF and ACPA together are even more specific

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Clinical features

 Pain and stiffness of the small joints of the hands (MCPs, PIPs) and feet (MTPs)
 The DIPs are usually spared
 Wrists, elbows, shoulders, knees and ankles are also affected
 In most cases, multiple joints are involved
 10% of patients present with a monoarthritis of the knee or shoulder or with carpal tunnel
 The pain and stiffness are significantly worse in the morning
 Sleep disturbance and fatigue are common
 The joints are usually warm and tender with some joint swelling
 There is limitation of movement
 muscle wasting
 Deformities and non--articular features develop if the disease cannot be controlled
 RA in older patients may mimic polymyalgia rheumatica; the synovitis becomes apparent as
the corticosteroid dose is reduced

Seronegative RA
Affects the wrists more often than the fingers

less symmetrical joint involvement

better long--term prognosis

can be confused with psoriatic arthropathy

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Complications

 Septic arthritis
This serious complication has significant morbidity and mortality

In immunosuppressed patients, affected joints may not display the typical signs of
inflammation with accompanying fever found in patients with an intact immune system.
Treatment is with systemic antibiotics (see p. 455) and drainage.

 Amyloidosis
found in a very small number of people with uncontrolled RA

RA is the most common cause of secondary AA amyloidosis

AL amyloidosis causes a polyarthritis that resembles RA in distribution and is also often

associated with carpal tunnel syndrome and subcutaneous nodules.

Joint Involvement

 Hands and wrists

Joint damage causes:

A combination of ulnar drift and palmar subluxation of the MCPs

Fixed flexion (buttonhole or boutonnière deformity)

Fixed hyperextension (swan--neck deformity) of the PIP joints

Swelling and dorsal subluxation of the ulnar styloid, which causes wrist pain

 Shoulders
 Elbows
 Feet
MTP joints

The foot becomes broader

hammer--toe deformity

Ulcers or calluses may develop under the metatarsal heads and over the dorsum of

the toes.

 Knees
 Hips
 C spine : Axial Involvement of RA***

146
  Other joints***
o Temporomandibular Non Articular Manifestations
o Acromioclavicular
o Sternoclavicular
o Cricoarytenoid
o any other synovial joint
can be affected
Vasculitis

Vasculitis is uncommon

widespread cutaneous vasculitis

with necrosis of the skin

mononeuritis multiplex

Risk factors include

high titres of RF

active extra--articular disease

elsewhere

Investigations

 Blood count may show a normochromic, normocytic anaemia

 ESR and/or CRP are raised in proportion to the activity of the inflammatory process and are
useful in monitoring treatment
 Serology reveals ACPA positivity that may be present early in the disease. In early
inflammatory arthritis indicates the likelihood of progressing to RA.
 RF is present in approximately 75–80% of cases
 ANA at low titre in 30%.
 X--rays show soft tissue swelling in early disease
 Ultrasound and MRI useful to demonstrate synovitis and early erosions.
 Aspiration of the joint may be needed if an effusion is present
o The aspirate looks cloudy owing to white cells
 Musculoskeletal ultrasound is a very effective way of demonstrating persistent synovitis
when deciding on the need for DMARDs or assessing their efficacy

Management of rheumatoid arthritis

 Establish the diagnosis clinically

 Use NSAIDs and analgesics to control symptoms
 Try to induce remission with intramuscular depot methylprednisolone 80–120 mg if
synovitis persists beyond 6 weeks

147
  If synovitis recurs, refer to a rheumatologist to start DMARDs
 Consider combinations of sulfasalazine, methotrexate and hydroxychloroquine
 Give a second dose of intramuscular depot methylprednisolone or oral steroids.
 Refer for physiotherapy and general advice through a specialist team
 As improvement occurs, tail off steroids and possibly reduce drugs
If no improvement use anti--TNF-­α therapy or other biologics

Spondyloarthritis (SpA)

Spond – spine, arthro – joints

Is an umbrella term for diseases affecting peripheral joints + spine

Linked to type 1 HLA antigens

Classification

Depending on which joints are mostly affected,

 Axial (ASpA) – spine &/or sacroiliac joints mostly affected

 Peripheral (PSpA) – arthritis, enthesitis, dactylitis

Distinctly recognized clinical presentations;

 Axial SpA (including ankylosing spondylitis)

 Psoriatic arthritis
 Reactive arthritis (sexually acquired)
 Post dysenteric reactive arthritis
 Enteropathic arthritis (Ulcerative colitis, Crohn’s disease)

 Ankylosing spondylitis

Male : Female = 3:1

Presentation –
 Back pain*
 buttock pain
 retention of lumbar lordosis in spinal flexion—>paraspinal muscle wasting
 anterior chest pain – costochondral inflammation
 flexion deformity of the hips
 lower limb monoarthritis
 Extra articular features
 Acute anterior uveitis (severe eye pain, photophobia and blurred vision)
 Aortic incompetence, cardiac conduction abnormalities
 Chest wall rigidity with ILD
 Renal impairment (with chronic NSAID use)
 Axial osteoporosis and vertebral fractures

148
 *criteria for diagnosing back pain as axial spondyloarthritis- 4/5 suggests Ank Spond with
great sensitivity
Age <45 years
Insidious onset
Improvement with exercise
No improvement with rest
Pain at night, improved on getting up
*Schoeber’s test

Investigations – ESR & CRP - elevated

X rays – eroding &/or sclerosis of SI joints, syndesmophyte(bony spurs) & ‘bamboo’ spine.

 Psoriatic arthritis

Presentations–

 Monoarthrits
 Oligoarthritis
 Polyarthrits
 Spondylitis –SI joints & early cervical spine involvement
 Distal interphalangeal arthritis – The most typical pattern. Dactylitis characteristic
 Arthritis mutilans – causes periarticular osteolysis + bone shortening – telescopic
fingers

X ray – ‘pencil in the cup’ appearance.

 Reactive arthritis

Sterile synovitis following an infection

Males are commonly affected

Aetiology –

In bacillary dysentery – Salmonella, Shigella sp.

Diarrhea – Yersinia enterocolitica
Non Specific Urethritis– Chlamydia trachomatis, Ureaplasma urealyticum

Presentation –

Acute, asymmetrical, lower limb arthritis

Enthesitis (Plantar fasciitis, Achilles tendinitis) /dactylitis (sausage toe)
Skin lesions – circinate balanitis, keratoderma blennorrhagica & nail dystrophy
Onset is few days – weeks after infection

149
  Enteropathic arthritis associated with IBD

o asymmetrical and predominantly affects lower limb joints.

o Joint symptoms may appear before the bowel symptoms
o Remission or cure of UC leads to remission of the joint disease, not in CD

Gout

 Gout is an inflammatory arthritis associated with

hyperuricaemia and intra--articular sodium urate
crystals.
 The involvement of the innate immune system and
inflammasomes indicates that gout is an
autoinflammatory disease
 Gout is more common in men than women (5 : 1);
it rarely occurs before young adulthood
 OA joints are more prone to attacks of gout
 SUA depends on the balance between purine
synthesis, ingestion of dietary purines and the
elimination of urate by the kidney (66%) and
intestine (33%).

 90% of people with gout have impaired excretion of

uric acid (10% have increased production due to
high cell turnover and <1% due to an inborn error of metabolism)

Clinical Manifestations

 may be asymptomatic
 Acute gout
 Chronic interval gout, with acute attacks superimposed on low--grade inflammation and
potential joint damage
 Chronic polyarticular tophaceous gout, which is rare and characterized by chronic joint pain,
activity limitation, structural joint damage and frequent flares.
 Urate renal stone formation
 Acute gout presents typically in a middle--aged male with a sudden onset of agonizing
pain, swelling and redness of the first MTP joint
o The attack may be precipitated by excess food, alcohol, dehydration or diuretic
therapy. Untreated attacks last about 7 days
o In 25% of attacks, a joint other than the great toe is affected
o Triggers for flares include acute medical or surgical illness, dehydration, or dietary
factors such as alcohol intake or purine--rich foods

 The clinical picture is often diagnostic, as is the rapid response to NSAIDs or colchicine

150
Investigations

 Joint fluid microscopy is the most specific and diagnostic test but is technically difficult
 Serum uric acid is usually raised (>600 μmol/L)
 Acute gout rarely occurs with SUA in the lower half of the normal range below the saturation
point of 360 μmol/L
 Serum urea, creatinine and estimated glomerular filtration rate (eGFR) are monitored for
signs of renal impairment

Management

 The use of NSAIDs or coxibs in high doses rapidly reduces the pain and swellings
 The first dose should be taken at the first indication of an attack
o Naproxen
o Diclofenac
 Colchicine
 Corticosteroids: oral prednisolone or intramuscular or intra-articular depot
methylprednisolone is used
 Allopurinol
o used when the attacks are frequent and severe (despite dietary changes), or
associated with renal impairment or tophi, or when the patient finds NSAIDs or
colchicine difficult to tolerate. Allopurinol is a xanthine oxidase inhibitor, which
reduces SUA levels rapidly
 Febuxostat
o a non--purine analogue inhibitor of xanthine oxidase that is well tolerated and as
effective as allopurinol
 Pegloticase

Septic Arthritis
 The organism that most commonly causes septic arthritis is Staphylococcus aureus
 Other organisms include
o Streptococci
o Neisseria gonorrhoeae
o Haemophilus influenzae
 Clinical features
Suspected septic arthritis is a medical emergency
o In young and previously fit people, the joint is hot, red, swollen and agonizingly
painful
o held immobile by muscle spasm
o In contrast, the onset may be insidious with a lack of systemic symptoms in the
elderly, the immunosuppressed and patients with RA, and a high index of suspicion
is needed

 In 20% of patients, the sepsis affects more than one joint

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 USS of the joint

 Management
o it is vital to treat on the basis of clinical suspicion
o The joint should be aspirated: send samples for culture and ABST
o Antibiotics should be started immediately before culture results are available
because joint destruction may occur within weeks
 Intravenous antibiotics should be given for 2 weeks and then oral
antibiotics for a further 4 weeks
o Immobilization
o early physiotherapy to prevent stiffness and muscle wasting
o Response is monitored clinically and with ESR and CRP
 Empirical Antibiotics
o Gram--positive infection first--line therapy is vancomycin
o clindamycin or cephalosporin second line
o Gram--negative infection first--line therapy is a third--generation cephalosporin with
IV ciprofloxacin second line
 Drainage of the joint and/or arthroscopic joint washouts are required in all cases

SLE
 Autoimmune rheumatic disease
 F:M = 9:1
 Peak age of onset between 20-40yo
 Aetiology- Heredity, genetics, sex hormone status (pre menopausal women more affected),
drugs (hydralazine, isoniazid, procainamide, penicillamine can induce a form of SLE), UV light
can trigger SLE, EBV is a trigger.
 Diagnosis and clinical features

152
153
  Disease flareup- Combination of high ESR, high anti- dsDNA and low C3
 CRP is usually normal, but may rise during serositis, coexistent infection

Pregnancy and SLE

 Exacerbations can arise during pregnancy and are frequent in postpartum

 Risk of neonatal lupus syndrome

154
APLS
 Thrombosis (arterial /venous) and/or recurrent miscarriages with persistently + APL abs =
APLS
 APL abs – anticardiolipin abs(IgG/IgM), lupus anticoagulants, anti beta 2 glycoprotein 1
antibodies
 Pathogenesis – APL ab target the body’s own phospholipids in the cell membrane
(endothelial cells, monocytes, platelets, tropoblasts). Alteration of function of those cells
lead to thrombosis and/or miscarriages.

Clinical features – 20% - ischemic strokes

40% - DVT
Thrombocytopenia
Chorea, migraine and epilepsy
Valvular heart dx
Cutaneous manifestations (e.g. livedo reticularis)
Positive Coombs test
Renal impairment due to ischemia in the small vessels.

 Catastrophic APLS – rare variant. Multiple infarcts in different organ systems causing
multiple organ failure.

Mx
 patient with one or more episodes of thrombosis – long term warfarin

 Pregnant mothers – aspirin and s/c heparin from early in gestation

o (This reduces chances of miscarriage but pre-eclampsia and IUGR is common)

 Patients with no thrombotic event – no definite guideline, aspirin and clopid can be given
prophylactically (when in high IgG) and warfarin is given prophylactically very rarely (esp.
when all 3 APL abs are +)

155
Systemic Sclerosis

 Systemic sclerosis is a multisystem

disease and has the highest case-
specific mortality of any of the
autoimmune rheumatic disease.
 Incidence - 10/million population
per year with 3: 1 female to male
ratio.
 Peak incidence is between 30 to 50
years.
 Environmental risk factors - vinyl
chloride, silica dust, adulterated
rapeseed oil, trichloroethylene and
drugs – Bleomycin.
 Raynaud’s phenomenon is seen in
almost all cases.
 Limited cutaneous scleroderma
(LcSSc): 70% of cases
 Diffuse cutaneous scleroderma
(DcSSc): 30% of cases
 Ix –
o FBC- NCNC anaemia
o MAHA in some with renal disease
o S. creatinine and urea raised in AKI
o Autoantibodies-
 anti- centromere antibodies (ACAs)
 anti- topoisomerase- 1 antibodies (anti- Scl- 70)
 anti- RNA polymerase antibodies.
 RF is positive in 30% and ANA is positive in 95%
o Urine microscopy - if there is proteinuria, the urine albumin/creatinine ratio should
be measured.
o Imaging- CXR, X-ray hands- acro-osteolysis, Barium swallow (impaired oesophageal
motility , Echocardiogram and lung function tests for pulmonary fibrosis or
pulmonary hypertension. HRCT: to demonstrate fibrotic lung.
 Management
o Education
o Regular exercise and skin lubricants,
o Hand warmers and oral vasodilators for Raynaud’s phenomenon.
o PPI for oesophageal symptoms
o malabsorption-nutritional supplements and rotational antibiotics.
o Renal involvement -ACE inhibitor
o Pulmonary hypertension -oral vasodilators, oxygen and warfarin.
o Advanced cases should receive prostacyclin therapy or bosentan
o Pulmonary fibrosis- immunosuppressants and low- dose oral prednisolone.

156
Polymyositis and Dermatomyositis
 Rare condition with insidious onset of progressive proximal symmetrical muscle weakness,
autoimmune mediated striated muscle inflammation (myositis) and myalgia +/- arthralgia.
 Myositis (esp.dermatomyositis) may be a paraneoplastic phenomenon of lung, pancreatic,
ovarian or bowel malignancies.
 Dermatomyositis – myositis + skin signs (shawl sign, heliotrope rash, Gottron’s papules, nail
fold erythema, subcutaneous calcifications)
 Extra muscular signs – in both conditions (fever, arthralgia, raynaud’s, ILD, myocarditis)
 Tests – Muscle enzymes (AST, ALT, LDH, CPK, aldolase) increase in plasma
o EMG
o Muscle biopsy confirms the disease.
 Mx – screen for malignancies, start prednisolone, immunosuppressant – MTX,
cyclophosphamide, cyclosporine, azathioprine. For skin dx – HCQ
(No direct MCQ on this topic yet)

Overlap syndrome
 Patient shows characteristic features of more than one ARD. Can be diagnosed more than
one ARD separately.
 SLE, APLS, systemic sclerosis, polymyositis and dermatomyositis, sjogrens syndrome

CPK levels

157
Side effects of drugs

MTX neutropenia, thrombocytopenia, abnormal liver biochemistry, oral

ulcers
Sulfasalazine skin rash, oral ulcers, neutropenia, thrombocytopenia, abnormal liver
biochemistry, athralgia

Azathioprine leucopenia, thrombocytopenia, pancraetitis, hepatic disorders,

hypersensitivity reactions

Mycophenolate mofetil nausea, vomiting, diarrhea, skin rash, oral ulcers, bone marrow
suppression
Cyclophosphamide haemorrhagic cystitis, leucopenia, alopecia, sperm abnormalities,
ovarian failure

Leflunamide diarrhea, neutropenia, thrombocytopenia, abnormal liver

biochemistry, alopecia, hypertension

Hydroxychloroquine bulls eye maculopathy

Drugs that are safe Azathioprine,

in pregnancy hydroxycloroquine,
sulphasalazine, ciclosporin,low
dose oral corticosteroids

Drugs Mycophenolatemofetil, MTX,

contraindicated in leflunamide, cyclophosphamide
pregnancy

158
Systemic vasculitis

159
Giant Cell Arteritis and Polymyalgia Rheumatica

 Large- vessel Vasculitis Polymyalgia rheumatica and Giant cell(temporal) arteritis are
systemic vasculitc illnesses of the elderly
 Both are associated with the finding of a giant cell arteritis on temporal artery biopsy.
 Rare under 50yrs.
 Giant cell arteritis (GCA) is inflammatory granulomatous arteritis of large cerebral arteries
which occur in association with PMR. .Presenting symptoms of GCA – severe headaches,
tender-ness of the scalp (combing the hair may be painful) or of the temple, claudication of
the jaw when eating, and tenderness and swelling of one or more temporal or occipital
arteries. The most feared manifestation is sudden, painless, temporary or permanent loss of
vision in one eye due to involvement of the ophthalmic artery.

 Systemic manifestations of severe malaise, tiredness and fever occur

Investigations in GCA-

o Normochromic,normocyticanaemia
o ESR is usually raised.(50–120mm/h)
o very high CRP
o Liver biopsy may be abnormal as in PMR
o Albumin may be low
o A temporal artery biopsy from the affected side is the diagnostic test.. The lesions
are patchy and the whole length of the biopsy (>1 cm long) must be examined; even
so, negative biopsies also occur.
o Ultrasound scanning of artery can be used.

Polymyalgia Rheumatica
 Age >50 yrs. Clinical history is usually diagnostic.
 Clinical features-sudden onset severe pain and stiffness of the shoulders, neck, hips and
lumbar spine: a limb girdle pattern. These symptoms are worse in the morning, lasting from
30 minutes to several hours.Up to 25% of patients may have some inflammation of
peripheral joints.
 One- third of patients develop systemic features of tiredness, fever, weight loss, depression
and occasionally nocturnalsweats.
 Investigation of PMR- raised ESR and/or CRP is a hallmark of this condition. Serum ALP and γ-
glutamyl-transpeptidase may be raised as markers of the acute inflammation.Anaemia (mild
normochromic, normocytic) is often present.Temporal artery biopsy shows giant cell
arteritis in 10–30% of cases, but is rarely performed.

 Treatment (GCA and PMR) -Corticosteroids.Corticosteroid treatment should reduce the risk
of patients who have PMR developing GCA. NSAIDs are less effective and should not be
used. GCA much higher doses of steroid needed. Starting daily doses of prednisolone are:
PMR: 15 mg prednisolone daily reduced gradually. Steroid- sparing immunosuppressive
agents are used in refractory cases. Calcium, vitamin D supplements, and sometimes
bisphosphonates are necessary to prevent osteoporosis while high- dose steroids are being
used.

160
Still’s disease (aka systemic onset JIA)
Accounts for 10% of JIA

Affects boys and girls equally, up to 5 years of age

After 5years, girls are commonly affected

Adult-onset Still’s disease is rare

Clinical features –

 High fever (>39C)

 Evanescent pink maculopapular rash, at the height of the fever
 Arthralgia
 Myalgia
 Arthritis
 Generalized lymphadenopathy
 Hepatomegaly
 Pericarditis
 Pleurisy

Ddx –

Malignancy, particularly neuroblastoma and leukemia

Infections

Investigations –

 ESR & CRP – elevated

 FBC – neutrophilia and thrombocytosis
 Autoantibodies – negative

Complications –

Macrophage activation syndrome (MAS), mostly following an infection or a change in medication

161
Osteoporosis

A disease characterized by low bone mass and micro-

architectural deterioration of bone tissue, leading to
enhanced bone fragility and an increase in fracture risk’.

 Bone density of 2.5 standard deviations (SDs)

below the young healthy adult mean value (T-
score ≤−2.5) or lower.
 1in 2 women and 1 in 5 men aged 50years will
have an osteoporotic fracture during there
lifetime.
 Pathogenesis-
Osteoporosis results from increased bone
breakdown by osteoclasts and decreased bone
formation by osteoblasts leading to loss of bone
mass.

 Clinical features- Vertebral fracture- sudden onset

severe back pain.
Pain from mechanical derangement, increasing
kyphosis, height loss and abdominal protuberance
may follow vertebral fracture. Colles’ fractures
typically follow a fall on an outstretched arm.
Fractures of the proximal femur usually occur in
older individuals falling on their side or back.

 Prevention and management –

o Symptomatic management.
 Calcium and vitamin D. Daily intake of 800–1200mh of calcium and 400–
800IU of vitamin D are recommended.
o Lifestyle measures.
 Weight-bearing exercise for 30 minutes three times a week may increase
BMD. Reduction of falls.

162
Osteomalacia
 Osteomalacia is defective mineralization of newly formed bone matrix or osteoid.

163
Clinical features

 Osteomalacia may be symptomatic and identified incidentally on routine investigations

following fragility fracture. When symptomatic, it characteristically causes muscle weakness
and widespread bone pain.
 Characteristic waddling gait with difficulty climbing stairs and getting out of chair.
Generalized bone pain and tenderness, dull aching pain worse on weight bearing and
walking. (Can be reproduced by pressure on sternum/tibia)

Investigations

 Serum alkaline phosphataseiselevated in 90% of cases.

 Low serum calcium, low phosphate and elevated PTH are each present
 Serum 25-hydroxyvitamin D3 is low, usually less than 25 nmol/L (10ng/mL). Serum FGF- 23 is
elevated in many people with tumour- induced osteomalacia and in hypophosphataemic
rickets. Plain radiographs show decreased bone mineralization. The characteristic finding in
osteomalacia is Loser’s pseudo fractures. Tetracycline- labelled bone biopsy is the gold
standard diagnostic test.
Treatment
 Vitamin D replacement. Treatment involves two stages – an initial loading stage to replenish
body stores of vitamin D, and a
 Subsequent maintenance phase to avoid repeat deficiency.

164
6. Hepatology

Clinical approach to the patient with liver disease

Investigative tests can be divided into:

• Blood tests:

- Liver 'function' tests: serum albumin and bilirubin; prothrombin time (PT)

- Liver biochemistry: serum aspartate (AST) and alanine aminotransferases (ALT) - an increase
reflects hepatocellular damage; serum alkaline phosphatase (ALP) and gamma-glutamyl
transpeptidase (y-GT) - an increase reflects cholestasis; total protein.

- Viral markers.

- Additional blood investigations; haematological, biochemical, immunological, markers of liver

fibrosis and genetic analysis

• Urine tests - for bilirubin and urobilinogen.

• Imaging techniques - to define gross anatomy.

• Liver biopsy - for histology.

Liver function tests

Serum albumin This is a marker of synthetic function and is useful for gauging the severity of chronic
liver disease: a falling serum albumin is a bad prognostic sign. In acute liver disease, initial albumin
levels may be normal. Interpretation of a low albumin can be difficult when other causes of
hypoalbuminaemia (e.g. malnutrition, urinary protein loss or sepsis) are present.

Bilirubin Serum bilirubin is normally almost all unconjugated. In liver disease, increased serum
bilirubin is usually accompanied by other abnormalities in liver biochemistry. Differentiation
between conjugated or unconjugated bilirubin is only necessary in congenital disorders of bilirubin
metabolism or to exclude haemolysis.

Prothrombin time Prothrombin time (PT) is also a marker of synthetic function. Because of its short
half-life, it is a sensitive indicator of both acute and chronic liver disease. Vitamin K deficiency should
be excluded as the cause of a prolonged PT by giving an intravenous bolus (10mg) of vitamin K.
Vitamin K deficiency commonly occurs in biliary obstruction, as the low intestinal concentration of
bile salts results in poor absorption of vitamin K.

Liver biochemistry

Aminotransferases These enzymes (often referred to as transaminases) are contained in

hepatocytes and leak into the blood with liver cell damage. Two enzymes are measured:

• Aspartate aminotransferase (AST) is primarily a mitochondrial enzyme (80%; 20% in cytoplasm)

and is also present in heart, muscle, kidney and brain. High levels are seen in hepatic necrosis,
myocardial infarction, muscle injury and congestive cardiac failure.

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• Alanine aminotransferase (ALT) is a cytosol enzyme, more specific to the liver, so that a rise only
occurs with liver disease. The ALT:AST ratio is a useful clinical indicator.

- In viral hepatitis, ALT is greater than AST unless cirrhosis is present, in which case AST is greater
than ALT.

- In patients with viral hepatitis, an AST: ALT ratio of more than 1 indicates cirrhosis.

- In alcoholic liver disease and steatohepatitis, the AST is often greater than the ALT.

- In patients with liver disease without cirrhosis, in whom AST is greater than ALT, alcohol or obesity
is the most likely aetiological agent.

Alkaline phosphatase

Alkaline phosphatase (ALP) is present in hepatic canalicular and sinusoidal membranes, and also in
bone, intestine and placenta. If necessary, its origin can be determined by electrophoretic separation
of isoenzymes or bone-specific monoclonal antibodies. In clinical practice, if y-GT is also abnormal,
the ALP is presumed to come from the liver. Serum ALP is raised in both intrahepatic and
extrahepatic cholestatic disease of any cause, due to increased synthesis. In cholestatic jaundice,
levels may be 4-6 times the normal limit. Raised levels also occur with hepatic infiltrations (e.g.
metastases) and in cirrhosis, frequently in the absence of jaundice. The highest serum levels due to
liver disease(> 1000 IU/L) are seen with hepatic metastases and PBC.

y-Glutamyl transpeptidase This is a microsomal enzyme present in liver, and also in many tissues. Its
activity can be induced by many drugs such as phenytoin, warfarin and rifampicin, and by alcohol. If
the ALP is normal, a raised serum y-GT can be a useful guide to alcohol intake. However, mild
elevations of y-GT are common, even with minimal alcohol consumption, and it is also raised in fatty
liver disease. In the absence of other liver function test abnormalities, a slightly raised y-GT can
safely be ignored. In cholestasis, they-GT rises in parallel with the ALP, as it has a similar pathway of
excretion. This is also true of 5-nucleotidase, another microsomal enzyme that can be measured in
blood.

Viral markers Viruses are a major cause of liver disease. Virological studies have a key role in
diagnosis;

Additional blood investigations

Haematological tests A full blood count may show thrombocytopenia. Thrombocytopenia is a

common finding in cirrhosis and is often aggravated by alcoholinduced bone marrow suppression

Biochemical tests

• a,-Antitrypsin enzyme deficiency can produce cirrhosis.

• a-Fetoprotein is normally produced by the fetal liver. Its reappearance in increasing and high
concentrations in adults indicates hepatocellular carcinoma

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Imaging techniques

Ultrasound examination

Computed tomography

Magnetic resonance imaging

Magnetic resonance cholangiopancreatography

Radionuclide imaging - scintiscanning

Jaundice

Jaundice (icterus) is detectable clinically when the serum bilirubin is >50 µmol/L (3 mg/dl). It may be
divided into:

• haemolytic jaundice - increased bilirubin load for the liver cells

• congenital hyperbilirubinemias - defects in conjugation

• cholestatic jaundice - including hepatocellular (parenchymal) liver disease and large duct
obstruction.

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Haemolytic jaundice
The increased breakdown of red cells leads to an increase in production of bilirubin. The resulting
jaundice is usually mild (serum bilirubin of 68-102 µmol/L, or 4-6 mg/dl), as normal liver function can
easily manage the increased bilirubin. Unconjugated bilirubin is not water-soluble and therefore
does not pass into urine: hence 'acholuric jaundice'. Urinary urobilinogen is increased. The causes
are those of haemolytic anaemia (pp. 531-533), and

clinical features of anaemia, jaundice, splenomegaly, gallstones and leg ulcers may be seen.
Investigations show haemolysis and elevated unconjugated bilirubin, but normal serum ALP,
transferases and albumin. Serum haptoglobins are low.

Congenital hyperbilirubinemias (non-haemolytic)

Unconjugated types

Gilbert syndrome This is the most common familial conjugated hyperbilirubinemia and affects 2-7%
of the population. It is asymptomatic and usually detected incidentally with a raised bilirubin (17-102
µmol/L, or 1-6 mg/dl). All other liver biochemistry is normal and there are no signs of liver disease.
There is a family history of jaundice in 5-15% of patients. Most patients have reduced levels of UDP-
glucuronosyl transferase (UGT-1) activity, the enzyme that conjugates bilirubin with glucuronic acid.
Mutations occur in the gene (UGT1A1 promoter region) encoding this enzyme, with an expanded
nucleotide repeat consisting of two extra bases in the upstream 5' promoter element. This
abnormality appears to be necessary for the syndrome, but is not in itself sufficient for clinical
manifestation (phenotypic expression). Establishing the diagnosis is necessary to provide
reassurance

and prevent unnecessary investigations. The raised unconjugated bilirubin is diagnostic and rises on
fasting and during mild illness. The reticulocyte count is normal, excluding haemolysis, and no
treatment is necessary.

Crigler-Najjar syndrome This is very rare. Only patients with type II (autosomal dominant) disease,
with a decrease in rather than absence (type I - autosomal recessive) of UGT survive into adult life.
Liver histology is normal. Transplantation is the only effective treatment.

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Conjugated types

Dubin-Johnson and Rotor syndromes Dubin-Johnson and Rotor syndromes (autosomal recessive)
are due to defects in hepatic bilirubin handling. The prognosis is good in both. In the Dubin-Johnson
syndrome, the liver is black owing to melanin deposition.

Cholestatic jaundice (acquired) This condition can be divided into extrahepatic and intrahepatic
cholestasis. The causes are shown in 14.8

Evaluate a Patient with jaundice

Important points in Hx

• Duration of illness. A history of jaundice with prolonged weight loss in an older patient suggests
malignancy. A short history, particularly with a prodromal illness of malaise, suggests an infectious
hepatitis.

• Recent outbreak of jaundice. An outbreak in the community suggests hepatitis A virus (HAV)

• Intravenous drug use, or recent injections or tattoos. These all increase the chance of HBV and
HCV infection.

• Men having sex with men. This increases the chance of HBV and HCV infection.

• Female sex workers. This increases the chance of HBV infection.

• Medical treatment in the developing world. There is an increased risk of HBV and HCV due to
poorly sterilized equipment or administration of unscreened blood or blood products.

• Alcohol consumption. A history of drinking habits should be taken, although many patients often
understate their consumption.

• Drugs (particularly those taken in the previous 2-3months). Many drugs, including over-the-
counter and herbal preparations, cause jaundice (see pp. 487-488).

• Travel. Certain areas have a high risk of hepatitis A virus (HAV) infection, as well as hepatitis E virus
(HEV), but HAV is common in the UK and HEV is common in travellers to the Indian subcontinent.

• Family history. Patients with, for example, Gilbert's disease may have family members who
experience recurrent jaundice.

• Recent surgery. Surgery on the biliary tract or for carcinoma is relevant.

• Environment. People engaged in recreational activities in rural areas, as well as farm and sewage
workers, are at risk for leptospirosis, hepatitis E and exposure to chemicals.

• Fevers or rigors. These are suggestive of cholangitis or possibly a liver abscess.

Clinical features

The signs of acute and chronic liver disease should be looked for

Certain additional signs may be helpful:

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 • Hepatomegaly. A smooth, tender liver is seen in hepatitis and in extrahepatic obstruction, but a
knobbly, irregular liver suggests metastases or cirrhosis.

• Splenomegaly. This indicates portal hypertension when signs of chronic liver disease are present.
The spleen can also be 'tipped' occasionally in viral hepatitis. In alcoholic cirrhosis, in particular, the
spleen may not be grossly enlarged and may not be palpable

• Ascites. This is found in cirrhosis but can also be due to other causes. A palpable gall bladder
occurs with a carcinoma of the pancreas obstructing the bile duct. Generalized lymphadenopathy
suggests a lymphoma.

Ix

Liver biochemistry In hepatitis, serum AST and ALT tend to be high early in the disease, with only a
small rise in serum ALP. Conversely, in extrahepatic obstruction, the ALP is high, with a smaller rise in
aminotransferases. However, these findings alone cannot be relied upon to make a diagnosis in an
individual case. The prothrombin time is often prolonged in longstanding liver disease, and the
serum albumin is also low.

Haematological tests In haemolytic jaundice, the bilirubin is raised and the other liver biochemistry
is normal. A raised white cell count may indicate infection (e.g. cholangitis). A leucopenia often
occurs in viral hepatitis, while abnormal mononuclear cells suggest infectious mononucleosis and a
Monospot test should be performed

Other blood tests These include tests to confirm the presence of specific causes of acute or chronic
liver disease, e.g. anti-mitochondrial antibody (AMA) for PBC. HIV status should be established

An ultrasound examination should always be performed

to exclude an extrahepatic obstruction, and to diagnose any features compatible with chronic liver
disease. Ultrasound will demonstrate:

• the size of the bile ducts, which are dilated in extrahepatic obstruction

• the level of the obstruction

• the cause of the obstruction in virtually all patients with tumours and in 75% of patients with
gallstones.

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171
Viral Hepatitis

 Hepatitis A always and Hepatitis E usually causes acute hepatitis. Hepatitis B, C, D can cause
acute or chronic hepatitis both.
 Hep A
 c/f – non specific. Anorexia, nausea, vomiting. Can be anicteric. Tender HM,
Lymphadenopathy Transient rash. Extrahepatic complications are rare.
- Ix – s. Bilirubin, AST/ALT > 1000 , ALP < 300, raised ESR, Lymphocytosis, anti-HAV
IgM in active dx
- Excellent prognosis. No specific mx.

 Hep B – HBV is not directly cytopathic. Damage is caused by host immune response

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-HBV specific cytotoxic CD8 T lymphocytes are involved in causing liver damage

- C/F – may be subclinical. Features are similar to HAV infection but more intense in severity. Extra
hepatic c/f are occasionally seen.

-Ix- Basic Ix are similar to HAV. Specific Ix are viral markers. Initially HBSAg is done. Full viral profile is
done only if that’s positive.

o Anti HBc-Ag is diagnostic

o HbsAg is cleared off from blood rapidly
o HBV DNA is the most sensitive diagnostic test for viral replication.

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Prognosis – Majority recover completely. 1% have acute liver failure.

- 1-10% develop chronic disease. The course of the disease depends mainly on pt’s age.

Management of acute hep B – symptomatic mainly. Entecavir/ Tenofovir can be given if HbsAg
persists beyond 12 weeks, or if the pt is very ill.

Chronic hepatitis B
-Chronic hep B pts may have histological changes from near normal to cirrhosis .

-Chronic HBV has 4 phases

- Phase 1 &2 HbeAg +ve chronic HBV

- phase 3&4 HbeAg -ve chronic HBV

Management- 3 criteria are used ; Serum HBV DNA levels, s. ALT levels, histological grade and stage.

-Patients with moderate to severe active necroinflammation and/or fibrosis in the liver, with
HBV DNA above 2000 IU/ mL (approximately 10 000 copies/mL) and/or ALT above the upper
limit of normal, are usually offered therapy. Age and co-morbidities also affect the decision
to treat and the choice of agent.

-If cirrhosis is present, treatment should be given, independent of ALT or HBV DNA levels.
Patients with decompensated cirrhosis can also be treated with oral antiviral agents but liver
transplantation may be required. All patients, regardless of disease phase, need long--term
followup, as transition to an active phase is common.

-the lifetime risk of malignancy is increased in all patients who are HbsAg positive.

- antiviral agents – Interferon / Entecavir/ Tenofovir

 Hep C

C/F – mostly asymptomatic. 10% have influenza like symptoms with jaundice and mild elevation of
transaminases. Most are diagnosed only after chronic illness.

Ix - HCV RNA, HCV Ab

Mx – In acute stage, monitoring for a few weeks with serial assessments of HCV RNA. If the viral load
is falling, treatment may not be required, but the patient should be observed for several months to
confirm true viral clearance. If the HCV RNA level does not decline, therapy is indicated. Needle-stick
injuries must be followed and treated early, although the vast majority (>97%) do not go on to
develop viraemia.

Prognosis- 85–90% of asymptomatic patients develop chronic liver disease. A higher percentage of
symptomatic patients ‘clear’ the virus, with only 48–75% going on to chronic liver disease.

Chronic HCV

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Chronic 16% of HCV infection causes slowly progressive fibrosis that leads, over decades, to
cirrhosis.

Factors associated with rapid progression of HCV fibrosis include excess alcohol consumption, co-
infection with HIV, obesity, diabetes

 Hep D

Can occur as a co infection with hep B or as a superinfection in a pt with chronic hep B.

Can lead to acute liver failure.

HDV RNA can be detected in both acute and chronic types.

60%-70% will develop cirrhosis

 Hep E

Infection doesn’t progress to cirrhosis unless the pt is immunocompromised.

Diagnosis- HEV RNA, Anti HEV IgG and IgM

Other causes of acute hepatitis – CMV, IMN, yellow fever, herpes simplex, toxoplasmosis

Acute liver failure

Acute liver failure (ALF) is defined as acute liver injury with encephalopathy and deranged
coagulation (INR >1.5) in a patient with a previously normal liver.

Commonest causes – viral hepatitis and PCM overdose

C/F – jaundice, small liver, features of hepatic encephalopathy, hyper reflexia, cerebral oedema

Raised ICP and brain herniation causes death in 25%

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176
Ix-

 Routine tests

hyperbilirubinemia, high serum aminotransferases and low levels of coagulation factors,

including prothrombin and factor v.

• An electroencephalogram (EEG) is sometimes helpful

• Ultrasound will define liver size and may indicate underlying liver pathology.

Autoimmune hepatitis
75% in females

40% have FHx of autoimmune dx and 20% have concurrent autoimmune dx

Liver damage is by CD4 T cells

Commoner in peri and post-menopausal ages

Ix – elevated transaminases, less elevated ALP a d bilirubin, elevated s. Gamma globulin,

- Normochromic normocytic anaemia, elevated PT

- Autoantibodies- ANA, Anti smooth muscle antibodies, anti LKM antibodies, rarely- anti
soluble liver enzyme antibody

Mx – prednisolone, azathioprine, MMF, tacrolimus, ciclosphorin

Cirrhosis

 Commonest causes – alcohol and NAFLD

 Pathology- micro and macro nodule formation. Micronodular cirrhosis - < 3mm nodules
uniformly distributed. Often caused by alcohol or biliary dx. Macronodular - nodules are
of variable size. Often caused by viral hepatitis

 Investigations
 Severity – liver functions (albumin, PT) / liver enzymes (maybe normal) / serum electrolytes (
low Na indicates severe dx ) / s. Creatinine (>130 micromoles/L indicates poor prognosis) /
biomarkers ( enhanced liver fibrosis test, elevated AFP indicated HCC )

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  Type –
• viral markers
• serum autoantibodies
• serum immunoglobulins
• iron indices and ferritin
• copper and caeruloplasmin
• α1--antitrypsin
• genetic markers. Serum copper and serum α1--antitrypsin should always be measured
in young cirrhotics. Total iron--binding capacity (TIBC) and ferritin should be measured to
exclude hereditary haemochromatosis; genetic markers are also available

 Imaging
 USS – changes in size and shape of the liver. Fatty change and fibrosis produce a
diffusely increased echogenicity. In established cirrhosis, there may be marginal
nodularity of the liver surface and distortion of the arterial vascular architecture. The
patency of the portal and hepatic veins can be evaluated. Ultrasound is useful for
detecting HCC.
 CT scanning –
 Endoscopy – to diagnose portal varices
 MRI – useful in the diagnosis of both malignant and benign tumours such as
haemangiomas. MR angiography can demonstrate the vascular anatomy, and MR
cholangiography the biliary tree.
 Liver biopsy – gold standard to diagnose type and severity

 Prognosis
 Prognosis is extremely variable. In general, the 5--year survival rate is approximately 50%,
depending on the stage at which diagnosis is made. Development of any complication usually
worsens the prognosis. There are a number of prognostic classifications based on modifications
of Child’s grading, Model for End--stage Liver Disease (MELD)

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Gut liver axis

 The liver is exposed to gut derived bacterial components that have little consequence in
health, as an effective gut barrier limits the number of bacterial components transported to
the liver.
 In advanced liver disease the intestinal barrier function is compromised due to changes in
gut motility, and suppression of gut immunological functions. This leads to bacteria and
bacterial components entering the portal circulation and being transported to the liver,
producing an inflammatory response.
 This cross-talk between the intestinal microbiota and the liver is referred to as the gut–liver
axis; it is seen as a key pathophysiological mechanism in the progression of liver disease and
development of the complications of cirrhosis.

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  Antibiotics and non-selective beta-blockers intercept the gut–liver axis by blocking bacterial
translocation, which is likely to account for their beneficial effects in reducing portal
pressure, variceal haemorrhage and spontaneous bacterial peritonitis.
 Absorbable antibiotics will lead to the selection of resistant bacteria. Rifaximin, a poorly
absorbed antibiotic used for encephalopathy, specifically affects the gut flora and has a low
risk for inducing resistance.

Liver transplantation

Indications

 acute liver disease

 Chronic liver disease
 Primary biliary cirrhosis
 Chronic hep B if HBV DNA negative
 Chronic hepatitis C
 Autoimmune hepatitis
 Alcoholic liver disease
 NASH cirrhosis
 Primary metabolic disorders – Wilson dx, hereditary haemochromatosis
 Other – sclerotic cholangitis, Polycystic kidney disease

Contraindications

 Active Sepsis (absolute)

 Anatomical considerations

Portal Hypertension
 The portal vein is formed by union of Superior mesenteric and splenic veins.
 Normal pressure is 5-8mmHg.
 Blood is returned to the heart via the inferior vena cava.
 Portal hypertension is classified according to the site of obstruction.
o Prehepatic - before the liver
o Intrahepatic - Distortion of the liver architecture
o Pre sinusoidal (Schistosomiasis)
o Post sinusoidal (Cirrhosis)
o Post hepatic - outside the liver(rare)

Portal pressure rises above 10-12mmHg

Compliant venous system dilates

Collateral form within systemic venous system 1. Gastro esophageal junction

superficial and tend to rupture

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 2.Rectum
Can differentiate from hemorrhoids
(are in lower anal canal)

3.left renal vein

4.Diaphragm

5.Retroperitoneum

6.Anterior abdominal wall via the

umbilical vein

Pathophysiology

Liver injury

Contraction of activated myofibroblasts

Mediated by endothelin,NO,Prostaglandin

Increased resistant to blood flow

Portal Hypertension

Opening of portosystemic anastomosis

 Neo angiogenesis also occurs.

 Hyperdynamic circulation of cirrhosis peripheral and splanchnic vasodilatation

Sodium retention

Plasma volume expansion

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  Ascites has a significant effect in maintaining portal hypertension.

Variceal Hemorrhage

Bleeding likely to occur with large varices, those with red signs at endoscope and in sever
liver disease.

Management

Can be divide into

1. The active bleeding episode

2. Prevention of rebleeding
3. Prophylactic measures to prevent the first hemorrhage
Prognosis ultimately depends on underlying liver disease.

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Initial management of acute variceal bleeding

Resuscitation
 Assess the patient: pulse, BP, Conscious state
 Insert a large-bore intravenous line and obtain blood for:
i. Grouping and
crossmatching
ii. Hb
iii. PT/INR
iv. BU,SE,S Cr
v. Liver biochemistry
vi. Blood culture
 Restore blood volume: With plasma expanders or,if possible blood transfusion.
Prompt correction,but not over correction as hypovolaemia is necessary in cirrhosis
patients(as their baroreceptor reflexes are diminished.)
Target Hb level- 80g/L
 Ascitic tap
 Monitor for alcohol withdrawal : IV thiamine
 Start prophylactic antibiotics: reduce early rebleeding and mortality.

Urgent endoscopy

Performed to

 To confirm the diagnosis

 To exclude bleeding from other sites (gastric ulcers) and portal hypertension/gastric antral
vascular ectasia(GAVE)

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  Variceal banding or injection of sclerotherapy

Other measures

Vasoconstrictor therapy

 Causes splanchnic arterial constriction restrict portal inflow

 Has shown benefit when used in combination with endoscopic techniques.

Terlipressin

o Is the only vasoconstrictor proven to reduce mortality.

o Dose- 2mg 6 hrly, reducing to 1mg 4 hrly after 48hr if a prolonged regimen is required (up to
5 days)
o Should not be given to patients with ischemic heart disease.
o Patient may complain of abdominal colic, may defecate, facial pallor due to generalized
vasoconstriction.

Somatostatin

o Dose – 250-500µg/hr
o Reserved for patients with contraindication to terlipressin.

Balloon tamponade

o Is used if endoscopic therapy has failed or if there is exsanguinating haemorrhage.

o The usual balloon tube is four-lumen Sengstaken-Blakemore
o Should be left in place for no more than 12 hrs and removed in the endoscopy room prior to
endoscopy.
o The tube is passed into the stomach and the gastric balloon inflated with air and pulled back.
o It should be positioned in close apposition to the gastro-oesophageal junction to prevent the
cephalad variceal blood flow to the bleeding point.
o The oesophageal balloon should be inflated only if bleeding is not controlled by the gastric
balloon alone.
o Complication: Aspiration pneumonia, oesophageal rupture, mucosal ulceration and
procedure is unpleasant for the patient.
o A self-expanding covered metal stent (Danis) can be introduced orally or endoscopically.

Additional management of the acute episode

1. Measures to prevent encephalopathy

2. Nursing: HCU/ICU care, Nil by mouth until bleeding has
stopped
3. Reduction in acid secretion: Ranitidine is preferred.

Management of an acute rebleed

o Occurs in about 15-20% within 5 days.

o Causes: ulceration, slippage of a ligation band
o Endoscopy should be performed once only to control rebleeding.
o If hemostasis cannot be achieved Transjugular intrahepatic portocaval shunt

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Transjugular intrahepatic portocaval shunt

o Used when bleeding cannot be controlled either acutely or following rebleed.

o Under X ray guidance, a guidewire is passed from the jugular vein into the liver and the portal
vein.
o It reduces the hepatic sinusoidal and portal vein pressure by creating a total shunt.
o Risk of portal systemic encephalopathy is increased.

Emergency surgery

o Performed rarely when other measures fail or if TIPS is not available.

o Surgery:
1. Oesophageal transection and ligation of the feeding
vessels to the bleeding varices.
2. Acute portosystemic shunt surgery

Prophylactic long-term measures

Non-selective beta blockers

o Oral propranolol or carvedilol

o Reduces resting pulse rate by 25% decreases portal pressure.
o Portal inflow is reduced by a decrease in cardiac output (β1) and by blockade of β2
vasodilator receptors on the splanchnic arteries, leaving an unopposed vasoconstrictor
effect.

Endoscopic treatment
o Repeated courses of banding at 2 weekly intervals leads to obliteration of varices.
o This markedly reduces rebleeding.
o Complications: oesophageal ulceration, mediastinitis, strictures

Combination therapy reduces overall bleeding compared to endoscopic therapy alone but
with no improvement in mortality.

Surgery
1. Surgical portosystemic shunt
2. Devascularization procedures
3. Liver transplantation

Prophylactic measures (primary prophylaxis)

o Patient with cirrhosis and significant varices that have not bled should be prescribed non
selective beta blockers.
o If there are contraindications, variceal banding is an option.

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Ascites (Fluid within peritoneal cavity)
Pathogenesis

Peripheral arterial vasoconstriction Portal hypertension Poor liver function

Reduction in effective blood volume Exerts a local hydrostatic pressure Low serum albumin
Activate sympathetic nervous Increased hepatic and splanchnic Reduce plasma oncotic
system & RAAS production of lymph pressure
Sodium and water retention Transudation of fluid into the
peritoneal cavity

Clinical features

Hx: Abdominal swelling, mild abdominal pain (if more severe, raise the suspicion on SBP) respiratory
distress, difficulty in eating accompany tense ascites

EX: Shifting dullness, peripheral oedema, pleural effusion (usually right sided) may infrequently be
found

Precipitating factors: high sodium diet, development of an HCC, splanchnic vein thrombosis

Investigations

A diagnostic aspiration of 10-20ml of fluid should be obtained for:

1. Cell count: A neutrophil count>250cells/mm3 indicative of underlying bacterial peritonitis

(usually spontaneous)
2. Gram stain and culture
3. Protein measurement: Serum-ascites albumin gradient (SAAG)
i. >11g/L—High—suggest portal hypertension
ii. <11g/L—low—associated with non-liver disease-
related abnormalities of the peritoneum(neoplasia)
4. Cytology: malignant cells
5. Amylase: exclude pancreatic ascites

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Management

The aim is both to reduce sodium intake and to increase renal sodium excretion

Producing a net reabsorption of fluid from the ascites into the circulating volume

 The maximum rate at which ascites can be mobilized is 500-700ml in 24hrs.

 Serum electrolytes, creatinine, eGFR (check alternative days)
 Daily measure weigh and UOP
 Bed rest
 Dietary sodium restriction (40mmol in 24hr, while maintaining an adequate protein and
calorie intake with a palatable diet)
 Drugs: avoid high sodium containing and sodium retaining drugs
 Fluid restriction: unnecessary unless the serum Na is <128mmol/L
 Diuretics: the choice is aldosterone antagonist-spironolactone—starting 100mg daily, can
gradually increase 400mg daily if necessary, providing there is no hyperkalaemia, chronic use
can cause gynaecomastia
o Aim of diuretic therapy produce a net loss of fluid 700ml in 24hrs (0.7kg weight
loss,1.0kg if peripheral oedema present)
o If response is poor can add loop diuretics--- furosemide 20-40mg/bumetanide0.5-1mg daily.
o Disadvantages--- hyponatremia, hypokalaemia, volume
depletion
o Diuretics should be temporary discontinued if there is--- rise in s.cr
 Hyperkalaemia
 Worsening of
encephalopathy
o Hyponatremia almost always represents haemodilution secondary to a failure to clear free
water(reduce renal perfusion) & diuretics should be stopped if sodium falls below
128mmol/L.

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Paracentesis

 Is used to relieve symptomatic tense ascites or when diuretic therapy is insufficient

 Complications: hypovolaemia and renal dysfunction (likely with >5L removal and worse liver
function)
 In patients with normal renal function and without hyponatremia, this is overcome by
infusing albumin.

Shunts

 TIPS may be inserted to treat resistant ascites, providing there is no spontaneous

portosystemic encephalopathy and with minimal disturbance of renal function.
 Frequency of paracentesis and diuretic use is reduced
 Nutrition and survival may improve.
 A peritoneo-bladder conduit has been developed for patient with advanced cirrhosis and
resistant ascites.

Spontaneous bacterial peritonitis

 Common organisms: Escherichia coli
Klebsiella
Enterococci
 Haematogenous spread
 Suspect when ascitic patient becomes deteriorates
 Pain and pyrexia are frequently absent
 Diagnostic aspiration should always be performed (raised neutrophil count)
 Tx—Broad spectrum antibiotics, subsequent alteration according to culture results
 Combine with human albumin solution infusion
 Non selective beta blocker should be stopped. (Increased risk of renal impairment)
 Secondary prevention---- Norfloxacin 400mg daily – prolongs survival
 Primary prophylaxis of SBP in patients with ascites protein <10g/L or sever liver disease may
prevent hepatorenal syndrome and improve survival.

Portosystemic encephalopathy
Chronic neuropsychiatric syndrome that is secondary to cirrhosis
PSE can arise in portal hypertensive patients due to spontaneous ‘shunting’, or in those with surgical
or TIPS shunts.

Pathogenesis

In cirrhosis, the portal blood bypasses the liver via collaterals, and ‘toxic’ metabolites pass directly to
the brain to produce encephalopathy.
Ammonia-induced alteration of brain neurotransmitter balance is the main mechanism
Other implicated substances are free fatty acids and mercaptans.

Factors precipitating portosystemic encephalopathy

• High dietary protein

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• Gastrointestinal hemorrhage
• Constipation
• Infection, including spontaneous bacterial peritonitis
• Fluid and electrolyte disturbance due to diuretic therapy or paracentesis
• Drugs (e.g., any central nervous system depressant)
• Portosystemic shunt operations, TIPS
• Any surgical procedure
• Progressive liver damage
• Development of hepatocellular carcinoma

Clinical features

Symptoms

 Acute Onset - increasingly drowsy and comatose

 Chronically – Change/fluctuation of personality, mood and intellect, with a reversal of
normal sleep rhythm.
 Other - irritable, confused, and disorientated, and has slow, slurred speech, hyper-reflexia
and increased tone
 Coma in marked encephalopathy
 Convulsions due to PSE is rare

Signs

1. fetor hepaticus (a sweet smell to the breath)

2. coarse flapping tremor (Asterixis)
3. constructional apraxia
4. decreased mental function (Serial sevens test)

Diagnosis – Clinical

Investigations (Additional)

1. EEG - decrease in the frequency of the normal α-waves (8–13Hz) to 1.5–3Hz.

2. Arterial blood ammonia
3. Visual evoked responses

Management

1. Identify and remove the possible precipitating cause

2. Give purgation (i.e. – Lactulose 10-30ml/tds) and enemas (Reduce ammonia absorption)
3. Nutrition (May need NG tube, No >48hrs protein restriction)
4. Antibiotics (Oral Rifaximin – secondary prevention of PSE or Metronidazole – beneficial
acutely)
5. Stop or reduce diuretics
6. IV fluids
7. Embolize collaterals that bypasses liver

Prognosis is very poor with acute encephalopathy in acute hepatic failure unlike in chronic PSE.

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Hepatorenal Syndrome
 The urine output is low with a low urinary sodium concentration, a maintained capacity to
concentrate urine (i.e., intact tubular function) and almost normal renal histology.
 Functional renal failure
 Precipitated by - over-vigorous diuretic therapy, NSAIDs, diarrhea, paracentesis, and
infection, particularly SBP

Mechanism (like that of ascites)

 extreme peripheral vasodilation > decreased effective blood volume and consequent
hypotension > RAAS activation > Renal vasoconstriction > low urine output with Na+ and
water retention

Management

1. Diuretic therapy should be stopped

2. intravascular hypovolemia correction - preferably with albumin + Terlipressin or
noradrenaline
3. Best option – liver transplantation

Hepatopulmonary syndrome

 Hypoxemia in patients with advanced liver disease due to intrapulmonary vascular dilation
with no evidence of primary pulmonary disease
 Most are asymptomatic. Severe disease – breathless on standing
 Typical patient – features of cirrhosis with spider naevi and clubbing, as well as cyanosis.
 Treatment – liver transplantation

Hepatocellular Carcinoma
Males > Females affected

Aetiology (arises in a cirrhotic liver in 95% of cases)

1. Carriers of HBV and HCV - extremely high risk! (HCV > HBV+HCV or HBV alone)
2. Alcoholic Cirrhosis
3. NAFLD-associated cirrhosis
4. Haemochromatosis
5. Aflatoxins
6. Androgenic steroids
7. Contraceptive pills (weak association)

Pathology – single or multiple nodules. Consists of cells resembling hepatocytes. Mets to LNs,,bones
and lungs

Clinical features

 The rapid development of include weight loss, anorexia, fever, an ache in the right
hypochondrium and ascites
in a cirrhotic patient is suggestive of HCC.
 On examination, an enlarged, irregular, tender liver may be felt.

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Investigations
1. Serum α-fetoprotein may be raised but is normal in at least a third of patients
2. CECT and MRI
3. US guided Tumor biopsy - now rarely done because seeding along the biopsy tract can occur

 Can be screened and detected by cross-sectional imaging and a rise in serum α-fetoprotein.

Management

 Liver transplantation offers the only opportunity for cure for patients with a small primary
tumor.
 Other options – Surgical resection, focal treatment (chemoembolization, radioembolization)

Primary biliary cholangitis (PBC)

 Progressive destruction of small interlobular bile ducts, causing cirrhosis in later stage.
 Destruction is believed to be immunological.
 Mitochondrial antigen M2 (specific to PBC), serum anti-mitochondrial antibodies(AMA), anti-
gp210(in 50% of patients) are found in patients.

Clinical features,

 Asymptomatic or
 Pruritus, fatigue, jaundice with hepatomegaly
 Pigmented xanthelasma on eyelids or cholesterol deposits in creases of hand may be
seen
 Other autoimmune disease may occur.

Management,

 Investigations,
o Mitochondrial antibodies
o Serum ALP - High
o Serum cholesterol - Elevated
o Serum IgM - Raised
o USS - altered liver architecture
o Liver biopsy – portal tract infiltration of lymphocytes/plasma cells

 Management,
o After excluding extrahepatic obstruction in jaundice patients,
o Ursodeoxycholic acid/ Obeticholic acid in unresponsive cases
o Fat soluble vitamin supplements
o Colestyramine for pruritus. Rifampicin/naloxone/naltrexone/ plasmapheresis
may be benficial.
o Liver transplant

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Primary sclerosing cholangitis
 Fibrosing inflammatory destruction of intra and extrahepatic bile ducts.
 Most of the time associated with IBD (usually ulcerative colitis)
 70% are men, average onset approximately 40 years
 Histology resemble “onion skin” appearance.

Clinical features,

 Asymptomatic
 Symptomatic – Pruritus, jaundice, cholangitis

Management,

 Investigation,
o MRCP
o Cholangiogram
 Management,
o Only proven treatment is liver transplant
o No evidence benefit in Ursodeoxycholic acid, bile acid
o If extrahepatic duct is involved, endoscopic interventions (balloon dilation,
temporary stent placement) are amenable

Secondary biliary cirrhosis

 A large duct biliary obstruction
 Causes include, bile duct strictures, gallstones and sclerosing cholangitis
 Ix- USS and MRCP
 Mx- ERCP/ percutaneous trans hepatic cholangiography

Hereditary haemochromatosis
 Inherited disease due to excess iron deposition in various organs.
 Four main types,
o Type 1 – HFE gene
o Type 2 – HV gene
o Type 3 – TfR2 gene
o Type 4 – ferroportin
 Pathophysiology – HFE gene protein interact with transferrin receptor (by disrupting the
hepcidine expression), which iron is absorbed exceeding the binding capacity of
transferrin.
 Cirrhosis is a late feature

Clinical features

 Classic triad – Bronze skin pigmentation, hepatomegaly, diabetes mellitus (Only in

gross iron overload)

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  Hypogonadism secondary to pituitary dysfunction
 Cardiac manifestation – heart failure, arrhythmias
 Arthropathy - Calcium pyrophosphate deposition in large and small joints
chondrocalcinosis)
 30% of people with cirrhosis will develop hepatocellular carcinoma.

Management

 Investigation
o Serum iron - >30mmol/l elevated
o TIBC – reduced
o Serum ferritin - >500micg/l elevated
o Transferrin saturation
o ALT/AST – often normal even in established cirrhosis
o Gene test – if iron studies are abnormal
o Liver biopsy – not required for diagnosis but for establish the extend of tissue
damage
o MRI
 Management
o Venesection – 500ml twice weekly for up to 2 years, while monitoring serum
iron/ferritin and MCV
o Iron chelation with desferrioxamine – for those who cannot tolerate venesection
due to sever cardiac disease/ anemia
o Screen all first degree family member

Wilson’s disease
 It’s an inborn error of copper metabolism, that results in copper deposition in various
organs
 Autosomal recessive disorder
 Pathophysiology, is failure of both incorporation of copper into procaeruloplasmin and
biliary excretion of copper. (Absorbed copper from stomach and upper small intestine is
transferred to liver and there it is incorporated to the apocaeruloplasmin forming
caeruloplasmin and excreted into the blood. Remaining copper excreted in the bile.)

Clinical features,

 Hepatic problems –Acute/Chronic/cirrhosis

 Neurological problems – tremor/dysarthria/dementia
 Chronic liver disease with neurological involvement.
 Kayser Fleischer ring

Management,

 Investigations
o Serum copper and caeruloplasmin – reduced or normal

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 o Urinary copper – increased usually
o Liver biopsy – aids diagnosis
o Genetic analysis
o Hemolysis and anaemia
 Management
o Lifetime treatment with penicillamine (effective in chelating copper)
o All siblings and children should be screened.
o Treat with zinc acetate, even if asymptomatic
o Diet low in copper such as chocolate, peanut is advidsed.

Alpha-antitrypsin deficiency
 Deficiency in alpha antitrypsin is associated with liver disease and pulmonary emphysema.
 Pathophysiology is uncertain. However, believed to be by failure of secretion of abnormal
protein accumulated in liver, leading to liver damage

Management,

 Investigation
o Serum alpha antitrypsin level – Low
 Management
o No definitive management. Only managing the complications of liver disease.

Alcoholic Liver Disease

 Liver is damaged by excessive consumption of alcohol.
 Damage is mainly in the centrilobular necrosis of the hepatic asinus.
 However, not all the heavy drinkers are get affected. Only 10%-20% of heavy alcohol
consumers develop cirrhosis. Therefore, a genetic predisposition is recognized.
 Alcohol can produce wide variety of liver damage, from fatty changed to hepatitis and
cirrhosis.

Fatty Liver,

 Metabolism of alcohol invariably produce fat in liver. But there is no liver damage. Fat
disappeared on stopping alcohol.
 In some cases, can progress into cirrhosis
 Often no symptoms and signs. Sometimes hepatomegaly can occur together with other
features of chronic liver disease.
 Ix
o MCV (elevated)
o ALT, AST – (elevated)
o Gamma GT (elevated)
o USS/CT – demonstrate fatty infiltration
o Elastography – Degree of fibrosis
 Mx
o Advise patient to stop drinking alcohol

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 Alcoholic hepatitis,

 In addition to fatty changes, there is infiltration by polymorphonuclear leucocytes and

hepatocyte necrosis mainly in zone 3.
 Mallory bodies are suggestive, but not specific for alcoholic damage.
 Clinical picture varies in degree
 Ix
o Leukocytosis
o Serum bilirubin
o AST, ALT
Elevated
o ALP
o PT
o Serum albumin – (low)
 Mx
o Sever cases need hospital admission
o Maintain nutrition with enteral feeding, vitamin supplements if necessary

Alcoholic cirrhosis,

 Classically of micro nodular type

 Represent the final stage of liver disease. Clinically manifest signs of chronic liver disease.
 Investigation and management as in cirrhosis.

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7. GI Disorders
Acute diarrhea
Acute Diarrhoea < 14 days

Infective
diarrhea

Viral Bacterial

Blood &
Watery
Mucous

Mucosal Mucosal
Cytotoxin invasion
Enterotoxin Adherence

Shigella
Salmonella Campylobater
Salmonella EPEC Campylobacter EIEC
Chloera EHEC
Campylobacter Clostridium
ETEC difficile
Bacillus Cereus
Clostridium perfringens
Clostridium difficile

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Organism Incubation period Symptoms Diagnosis
Salmonella 12-48 hrs. Nausea, Abdominal pain, watery Stool culture
or B&M diarrhea
Shigella 24-48 hrs. Acute watery or B&M diarrhea Stool culture
Campylobacter 4-96 hrs. B&M diarrhea, fever, malaise, ab Stool culture
pain
Bacillus cereus 1-6 hrs. Vomiting, diarrhea Stool/Food culture
6-14 hrs.
ETEC 24 hrs. Watery diarrhea Stool culture
E coli o157:H7 12-48 hrs. Watery diarrhea, hemorrhagic Stool culture
colitis, HUS
Clostridium botulism 18-24 hrs. Brief diarrhea followed by Toxin in food /stool
paralysis
Clostridium difficile 2 days-few months after Watery diarrhea, hemorrhagic Stool ELISA/ PCR for A &B toxins
antibiotic use colitis, Abdominal pain, Colonic
pseudo membranes
Staph aureus 2-4 hrs. Violent vomiting, Watery Vomitus/food culture
diarrhea

Acute diarrhoea management

1) Fluid resuscitation
2) Antibiotics
 Campylobacter – Azithromycin 500mg once daily (Co trimoxazole)
 Clostridium difficile – Metronidazole 400mg tds (Vancomycin)
 Others- Ciprofloxacin 500mg bd (Ampicillin, Azithromycin, Cotrimoxazole)
3) Treat complications
AKI, sepsis, perforation

Traveler’s diarrhea

 3 or more unformed stools per day in a person from a developed country travelling
in a developing country
 Mostly ETEC. Can also be by salmonella, shigella, campylobacter, vir

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Chronic Diarrhoea

 Passage of 3 or more loose stools (Bristol stool chart >4) per day is diarrhoea.
 Chronic = diarrhoea > 4 weeks

Causes

Evaluation

 Thorough history is important.

- Small bowel vs large bowel type of diarrhoea

--> small bowel = large volume, bulk, undigested food, a/w periumbilical pain

--> large bowel = small volume, blood and mucus, tenesmus, sensation of incomplete
evacuation

- Identify the possible causes

- Assess complications

--> dehydration

--> Electrolyte imbalances

--> Malnourishment

--> Vitamin deficiencies

 A full examination is needed.

 Chronic diarrhoea always needs Investigation.

- Initial Ix should include,

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 --> FBC, S.Creatinine, SE, Thyroid function tests

--> Stool microscopy, culture, full report

--> Coeliac screening

--> Faecal calprotectin

- If above do not reveal a causes, patient should undergo a flexible sigmoidoscopy. However in
following circumstances a full colonoscopy should be done.

--> Iron deficiency anaemia

--> Abnormal faecal Calprotectin with suspicion of IBD

--> Older patients with suspicion of colorectal malignancies

- Further investigations include.

--> CT/MRI, capsule endoscopy

--> SeHCAT scan

Pathophysiology

Osmotic Secretory Inflammatory Abnormal

motility/functional
Due to; Due to; Due to; Due to;
 Non absorbable  Enterotoxins  Infections  DM
substance ingestion  Hormones  Inflammation  Hyperthyroidism
 Generalized/specific (VIP) (IBD)  Post-vagotomy
Defects in  Bile salts in
absorption ileal resection
 Fatty acids

Fasting improves diarrhea No effect by fasting No effect by fasting No effect by fasting

Watery Watery Blood & mucous Watery

Bile acid Malabsorption

 Occur when terminal ileum fails reabsorb bile acids.

 Ileal resection, Crohn’s dx
 Diagnosed bu SeHCAT test. (radiolabeled bile acid analogue given)
 Tx - Cholestyramine

C.difficile associated Diarrhoea

 May develop following the use of any antibiotic. But broader the spectrum of the antibiotic,
higher the chance.
 Can develop in the first few days or even 6 weeks after stopping.
 Demonstrating C.difficile toxins in stools or pseudomembranous colitis in endoscopy helps in
diagnosis.
 Tx - oral Vancomycin or oral Metronidazole

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Diarhhoea in HIV patients

 Can be due to,

 Infections eg. Cryptosporidium
 Malignancies eg. Lymphoma
 ART

Coeliac disease (gluten-sensitive enteropathy)

 An autoimmune condition.
 Improves when gluten is withdrawn from the diet and relapses when gluten is reintroduced.
 Diagnosis
 Gold standard is the small bowel biopsy.
 Serology - Endomysia (EMA) and tissue transglutaminase (tTG) antibodies.
 HLA typing
 HLA-DQ2 is present in 90–95% patients
 Management
 Gluten free diet for lifetime.
 Replacement of vitamins and minerals.

Irritable bowel syndrome (IBS)

 Most common functional gastro-intestinal disorder.

 Anxiety and depression are more common in IBS patients.
 Stressors, adverse life events precede the onset of chronic bowel symptoms.

 Diagnosis

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  Diagnostic criteria(Rome IV 2016) - at least 1 day per week in the last 3 months of recurrent
abdominal pain associated with two or more of the following:
1. Related to defecation.
2. Onset associated with a change in frequency of stool.
3. Onset associated with a change in form (appearance) of stools.
 Management

Inflammatory Bowel Disease

 Two major forms.

1.Crohn’s disease (CD)- can affect any part of the gastro intestinal tract 2.Ulcerative colitis (UC)-
affects only the colon

 Aetiology - Due to interaction between several co factors : genetic susceptibility, the

environment, the intestinal microbiota and host immune response

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202
203
Management
Management of Crhon's disease

 Surgical management of Crohn’s disease

 The indications for surgery are:
 Failure of medical therapy
 complications(e.g.toxic dilation, obstruction, perforation, abscesses, enterocutaneous
fistula)
 Failure to grow in children despite medical treatment
 Presence of peri anal sepsis

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Management of ulcerative colitis
Medical management

 Main stay of treatment for mild and moderate disease of any extention --> aminosalicylate,
which acts topically in the colonic lumen. (Active substance is 5ASA)
 Aminosalicylates maintain remission in all forms of disease
 Proctitis
 Rectal 5-ASA suppositories are the first line treatment.
 Oral 5-ASA can be added to increase remission rates
 Oral prednisolone
 Left-sided colitis
 Topical 5-ASA enemas are the first line treatment.
 Addition of an oral 5-ASA will increase remission rates.
 Oral prednisolone.
 Extensive colitis
 Oral 5-ASA.
 Additional of a 5-ASA enema increases remission rates.
 Oral prednisolone
 Refractory / severe colitis of any extent
 Receive biological therapy with either an anti TNF agent (infliximab, adalimumab)

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8. CVS

Examination of the CVS

General Examination
Sign Description causes
Clubbing Congenital cyanotic heart
diseases – fallot’s tetralogy
Subacute infective
endocarditis (10%)
Splinter hemorrhages small, subungual linear Trauma
hemorrhages Infective endocarditis
Cyanosis Central – right to left shunts

Peripheral - peripheral Congestive heart failure

vasoconstriction Circulatory shock

Arterial pulse
Rate Normal – 60 -80/min
Rhythm Premature beats

Atrial fibrillation – irregularly irregular (persists when the pulse quickens in

response to exercise, in contrast to pulse irregularity due to ectopic beats,
which usually disappears on exercise)

Character Corrigan’s sign in carotid pulse – AR/ high output states (thyrotoxicosis,
anemia, fever)

Collapsing pulse – AR/ PDA

Low volume – cardiac failure, shock, obstructive valvular diseases,

tachyarrhythmias

Plateau pulse – AS

Pulses alternans – regular alternate beats that are weak and strong – severe
myocardial failure

Bigeminal pulse – premature ectopic beat following every sinus beat

Pulses bisferiens – hypertrophic cardiomyopathy/ mixed aortic valve disease

Blood pressure

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Jugular venous pressure
Causes for elevated JVP –

- Heart failure/ congestive cardiac failure

- Constrictive pericarditis
- Cardiac tamponade
- Renal disease with salt and water retention
- Over transfusion/ excessive infusion of fluids
- SVC obstruction

Jugular venous pressure wave

3 peaks (a, c, v) and 2 troughs (x, y)

a wave – produced by atrial systole

x descent – occurs when atrial contraction finishes

c wave – due to transmission of RV systolic pressure before the tricuspid valve closes

v wave – occurs with venous return filling the RA

y descent – when the tricuspid valve opens

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Auscultation
 S1 – mitral and tricuspid valve closure
- loud – thin individuals, hyperdynamic circulation, tachycardias, mild to moderate mitral
stenosis
- soft – obesity, emphysema, pericardial effusion, severe calcific mitral stenosis, MR, TR,
heart failure, shock, bradycardias, 1st degree heart block

 S2 – aortic and pulmonary valve closure

 3rd heart sound – pathological (volume overload)

- due to rapid ventricular filling
- present in heart failure

 4th heart sound – pathological (pressure overload)

- AS, severe systemic HTN, LV outflow obstruction as in hypertrophic cardiomyopathy
- produces a gallop rhythm

Hypertension

Hypertension is largely asymptomatic, though it is associated with increased prevalence of headaches,

epistaxis and, less commonly, other neurological symptoms such as visual disturbance and dizziness.

History

 symptoms of hypertension
 secondary causes
 lifestyle issues: weight, alcohol excess, stimulant recreational drug use, tobacco smoking,
exercise, stressors (work and personal)
 family history
 pregnancy
 Adherence to antihypertensive.

Examination

1. Office measurement - measurement of the BP by a healthcare professional in a healthcare

setting
2. Home measurement - measurement of BP at home by the patients themselves

208
 3. Ambulatory measurement - measure BP discontinuously throughout a 24-hour period, most
commonly every 20–30 minutes during waking hours and every 30–60 minutes during sleep.

Correct BP measurement method - remember

209
Different types of Hypertension
1. Isolated systolic hypertension - Due to age-related arterial stiffening, systolic BP continues to
rise in patients above 50 years of age, with a corresponding reduction in diastolic BP. Drug
treatment in isolated systolic hypertension is the same as for combined hypertension. Aortic
valve incompetence can also cause an isolated systolic HTN.
2. Orthostatic hypotension - sustained fall in BP within 3 minutes of assuming an upright
position of either more than 20 mmHg systolic or more than 10 mmHg diastolic BP. It is more
common in older age and conditions associated with autonomic neuropathies. Most
guidelines recommend using the standing BP as the true BP value.
3. Variable blood pressure - degree of variability is exaggerated in some patients and often due
to disorders of the autonomic nervous or endocrine system. Need ambulatory BP monitoring.
Managed at specialist clinics.
4. White-coat hypertension - BP is elevated in the office, but is normal when measured by
ABPM, HBPM, or both.
5. Masked Hypertension - 15% of patients with a normal office BP has this. The prevalence is
greater in younger people, men, smokers, and those with higher levels of physical activity,
alcohol consumption, anxiety, and job stress. Masked hypertension has also been found to
increase the risk of CV.
6. Resistant hypertension - usually defined as uncontrolled BP despite three separate, guideline-
recommended antihypertensive. Adherence issues and causes of secondary hypertension
should be checked.

CAUSES

1. Primary hypertension (no cause)/ essential hypertension - 90% of patients have this
2. Secondary Hypertension - can have an identifiable singular cause. It relatively is higher in
those under 30 years of age. But still commonest cause for young HTN is primary HTN.
Commonest secondary causes are primary hyperaldosteronism (increased salt/water
retention), obstructive sleep apnoea and obesity
3. Pregnancy induced Hypertension - women with hypertensive disorders of pregnancy are more
likely to develop hypertension earlier than others.

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HMOD – Hypertension mediated organ damage
The following assessments to detect HMOD should be performed routinely in all patients with
hypertension:

 Serum creatinine and eGFR

 Dipstick urine test
 12-lead ECG

1. Brain - TIA or strokes are common manifestations of elevated BP. Early subclinical changes can
be detected most sensitively by magnetic resonance imaging (MRI) and include white matter
lesions, silent micro infarcts, micro bleeds, and brain atrophy. Due to costs and limited
availability brain MRI is not recommended for routine practice but should be considered in
patients with neurologic disturbances, cognitive decline and memory loss.

2. Heart - A 12-lead ECG is recommended for routine workup of HTN.

3. Kidneys - Kidney damage can be a cause and consequence of hypertension and is best assessed
routinely by simple renal function parameters (serum creatinine and eGFR) together with
investigation for albuminuria (dipstick or urinary albumin creatinine ratio [UACR]) in early
morning spot urine).

4. Eyes - Fundoscopy is a bedside test to screen for hypertensive retinopathy. Fundoscopy is

particularly important in hypertensive urgencies and emergencies to detect retinal
haemorrhage, micro aneurysms, and papilledema in patients with accelerated or malignant
hypertension. Fundoscopy should be performed in patients with grade 2 hypertension.
a. Mild - arteriolar narrowing, and arteriovenous nicking (modest association with
cardiovascular and cerebral events).
b. Moderate - Haemorrhage (blot, dot or flame-shaped), micro aneurysm, cotton-wool
spot, hard exudate, or a combination of these signs (strong association with
cardiovascular and cerebral events).
c. Severe - Signs of moderate retinopathy plus papilledema (swelling of optic head)
(strong association with cardiovascular events, stroke and death).

Treatments – look at the chart

1. Lifestyle changes – given to all patients main thing is DASH diet where salt and fat
consumption is reduced and K, vegetable intake is increased and it is tailor made to individual
patient.

2. medications – as mentioned in following chart main thing is using combine medications in

lower doses so in most patients start with CCB + ACEI low doses.

3. Procedures / device based HTN treatment – in special cases only. Renal nerve denervation,
BAT- barro-reflex activation therapy, central arteriovenous fistula.

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 You can see main thing in
lifestyle change is changing
the diet. Other things also
helps.

Special points.
1. When there is non-adherence look problems in healthcare system, then medications (side effects,
availability, and cost) then patient factors.
2. HTN in pregnancy give Labetalol (BB), Nifidipine or methyldopa. (avoid other drugs)
3. HTN in children is >95th centile for age, sex and height – there are specific charts.
4. Black ethnicity has low renin status and ACEI or ARB may not be effective.
5. ARB is better tolerated due to less cough and less chance angioedema.
6. Rheumatoid arthritis and psoriatic arthritis increase the CV risk in patients with Hypertension.
7. Beta Blocker as 1st line anti-hypertensive is used in
a. Angina
b. Previous MI
c. Compensated HF/ Asymptomatic LV dysfunction
d. Pregnancy induced Hypertension
e. AF
f. Hyperthyroidism
8. Less than 1 in 5 people have HTN under control
9. 26% of total population have HTN.
10. More in male( 1 in every 4 male vs 1 in every 5 female)
11. Patient with psychiatric diseases avoid CCB as drug reactions can cause orthostatic hypotension.
12. HIV drugs also can have reactions with DHP-CCB
13. Older patients can have orthostatic hypotension with CCB
14. Treating resistant HTN – uncontrolled BP with 3 antihypertensive one of which must be a diuretic.
Do as following steps.
a. Think of secondary causes
b. Check medications
c. Check adherence
d. Add spironolactone
e. Add BB(labetalol, carvedilol)
f. Add direct vasodilators ( hydralazine, Minoxidil)
g. Add clonidine
15. HTN in CKD use ACEI or CCB they reduce proteinuria thus reduce disease progression.

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213
 Hypertension management at a Glance

Remembering this would be enough for but read everything carefully.

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Coronary artery disease

Myocardial ischaemia most commonly arises as a result of obstructive coronary artery disease (CAD)
in the form of coronary atherosclerosis. CAD common in male. Atherosclerosis is a complex
inflammatory process. 30–40% of Atherosclerotic disease manifest in one vascular bed is often
advanced in other territories.

Types of angina
1. Typical angina is characterized by chest pain:
a. ‘Heavy’, ‘tight’ or ‘gripping’ central or retrosternal pain may radiate to the jaw
and/or arms.
b. Pain occurs with exercise or emotional stress.
c. Pain eases rapidly with rest or with GTN.
2. Atypical angina is described as chest pain with 2 out of 3 of the features above.
3. Non-angina chest pain is described as chest pain with 1 out of 3 of the features above.
4. Stable angina
5. Unstable angina refers to angina of recent onset (<24 h) or deterioration in previous stable
angina, with symptoms frequently occurring at rest
6. Vasospastic or variant (Prinzmetal’s) angina refers to angina that occurs without
provocation, usually at rest, as a result of coronary artery spasm. It occurs more frequently
in women. Characteristically, there is ST segment elevation on the ECG during the pain.

A. Stable angina
The prevalence of angina increases with age
The diagnosis of angina is largely based on the clinical history

First see whether it is acute or chronic chest pain if acute chest pain need 12lead ecg to identify ACS.
Chronic pain suggest stable angina. History directed to identify risk factors and grading of angina. In
the examination look for followings

Risk factors As above

Causes Aortic stenosis murmur & other peripheral signs
Exacerbating factors anaemia, thyrotoxicosis, Heart failure
Co-morbidities Hypertension, obesity, DM

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Angina is an arterial disease when u see problem in one arterial system (coronary arteries in this case)
we have to inquire other arterial systems.

Cerebrovascular system Stroke. History of paralysis and pronator drift

PVD Claudication ,erectile dysfunction, peripheral pulses
Abdomen (not a must always but in History of mesenteric ischaemia, and Abdominal aortic aneurism in
surgery PVD case look for AAA) examination(AAA) ( pulsating abdominal mass)
Reno vascular History of CKD
Investigations are directed to identify same things we look in history and examination.

Initial investigations  FBC(anaemia), TFT(thyrotoxicosis),

 FBS and HbA1c (DM), Lipid profile,
 S.cr, Serum electrolyte
 ECG ( rhythm abnormality and past MI changes, LV hypertrophy)
 Ambulatory ECG( in Prinzmetal’s angina, arrhythmias)
 CXR( atypical presentations, HF)
Stress testing( not in all  Exercise ECG
patients and not all the  Pharmacological stress ECG ( use dobutamine to stress the heart)
tests)  Stress echo
 Nuclear imaging
Angiography  CT angiography – low probability of the disease do this as it is less invasive
 Invasive coronary angiography – GOLD std test
Done in severe angina and if planning to do interventions

IN Any test using exercise as stress arthritis, claudication, asthma, HF are contra-indications

Management

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 General measures 1. Lifestyle
2. Education
3. Optimize co-morbidities
4. Treat exacerbating factors
Anti-ischaemic drugs 1. 1st line- BB/CCB
Easier to memorize the 2. 2nd line – BB+CCB
chart 3. 3rd line – BB+DHP-CCB
4. 4th line – nicorandil
Stop recurrence 1. Aspirin
These drugs have mortality 2. Clopidegrel – if aspirin not tolerated( high risk can give both)
benefits 3. Bb
4. ACEI – has plaque stabilizing effect as well
Revascularization 1. PCI
2. CABG- most effective but high post op mortality than PCI

B. Acute coronary Syndrome (STEMI, NON-STEMI and UA)

The difference between UA and NSTEMI is that, in the latter, there is occluding thrombus.

NON-STEMI and UA

Need 7 ECGs. Initial ECG (no st elevation) – DO 3 ecgs in 10 minute intervals (30minutes) – Do another
3 ECGs in 30minutes interval. If all the ECGs are normal DO TropI levels in 6th hour and 12th hour after
the onset of chest pain.

 If no st elevation and tropI positive – NONSTEMI

 No st elevation and tropI negative – UA
 If any of the ECGs show st elevations (2 or more contiguous leads) , new BBB –
STEMI

Management

1. O2 if saturation is below 90%

2. Bed rest
3. Iv morphine 0.15mg per kg with 10mg of metoclopramide
4. Antiplatelet: Aspirin – 300mg , Clopidogrel – 300mg , Statin – 80mg (atorvastatin)
5. Nitrates: reduces afterload, reduces preload, reduce wall stress
a. Sublingual GTN(0.3mg) every 5minutely 3 doses
6. Beta-blockers: metoprolol/ carvedilol ( start during 1st 24h)
a. CI- heart failure. asthma, heart block, (relative CI)
7. CCB: initially non DHP-CCB ( verapamil, diltiazem )
8. ACEI: if having EF<40%, HTN, DM, CKD
9. Anticoagulants
a. Heparin 5000 IU Iv bolus + 0.25 units/kg per hour infusion
b. Or LMWH (enoxaparin) 1 mg/kg s.c. ×2 daily
c. Newer drugs – Fondaparinux, Rivaroxaban
10. Myocardial revascularization

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 Very high-risk patients HF, shock, VT, VF, pain not urgent coronary angiography (<2
resolving h)

high-risk patients dynamic ST-or T-wave within 24 h.

changes, or elevated GRACE
scores
Intermediate-risk patients DM, CKD within 72 h.

Low risk Revascularization is preferred

Heparin LMWH

 Need APTT monitoring  More effective

 Can use in CKD (eGFR<15)  Less risk of PLT reduction
 Antidote is more  Less bleeding risk
effective(protamine)  More bioavailable
 Cannot use if eGFR <15
 Less effective reversal with protamine

STEMI

Time targets

1. First medical encounter to ECG and diagnosis – 10min

2. STEMI diagnosis to primary PCI - <120min
3. In a PCI capable hospital From diagnosis to wire crossing( PCI 1st step) - <60min
4. Transferred patient to wire crossing - <90min
5. If not going for PCI, STEMI diagnosis to thrombolysis - <10min
6. Succes thrombolysis to routine PCI – 2 to 24 hours ( all patients after thrombolysis
should go for PCI)
7. After thrombolysis succes is assesed – 60 to 90min

Diabetes management in MI
 Monitor frequently
 If on metformin and SGLT-2i monitor renal functions
 Avoid hypoglycaemia, so only treat hyperglycaemia if plasma glucose is >180mg/dl

218
Imaging in MI

 Emergency ECHO – HF, suspected valvular complication but don’t delay PCI for this
 No CT-angio in acute setting

219
Day 1- after thrombolysis start followings

1. Asprin 75mg
2. Clopidogrel 75mg
3. Atovastatin 40mg
4. Enalapril start from small dose and increase upto 10mg bd (max tolerable)
5. BB( metoprolol) startfrom small dose increase upto 50mg bd (max tolerable)

Day 3/4 chest pain

 DD: reinfarction, post mi angina, acute pericarditis, GORD

 Mx:
o ABC
o Analgesics
o ECG urgent – further management depend on the findings
o Give antacids

Day 5 Dizziness/ low bp

 DD: postural hypotension (ACEI), bradycardia(BB), anaemia(GI bleeds due to anticoagulants and
antiplatelets), Anaphylaxis to newly started drugs, Reinfarctions
 MX:
o History- chest pain(another MI), SOB(anaphylaxis,HF)
o Ex-
 RV infarction- elevated JVP, lungs clear
 Anaphylaxis – increased RR, Ronchi, rashes
 GI bleeds – malena, pallor
o DO urgent ECG

Advices on discharge
1. Introduce medications
2. Driving – after 4weeks
3. Sex – untill can climb two flights of stairs ( 4weeks)’ start slowly and gradually increase
4. Stop smoking
5. Weight reduction if necessary
6. Cardiac rehabilitation program
7. 4weeks of medical leave
8. Dietaey advice
9. Exercise – start from samll get to 30min of aerobic per day 5 times per week
10. GTN advices
a. Maximum 3 tablets 5minutes apart
b. Sublingual use
c. If not resolving after 3rd tablet seek medical support
d. Keep in brown bottle, avoid direct sunlight
e. Take while seated
f. Renew every month
11. Ask to follow up
12. Safe alcohol use
13. Control co-morbidities (DM,HTN)

220
Clinic Follwup
1. 1st visit after 2 weeks to renew medications
2. Enrol on cardiac rehabilitation programme
a. Make patient functionaly normal after life changing event
b. Education, complication management, drug side effects
c. Exercise programmes
3. Optimize BB and ACEI
4. Antiplatelet treatment
a. Dual antiplatelet for 1 year
5. Asses cardiovascular risk do angio acordingly
a. GRACE score – 10 year CVD risk
b. High risk – angiogram
c. Low risk – CT angiogram
6. Further followup
a. 2d ECHO
i. Before discharge
ii. Repeat in 6weeks
iii. EF, wall motion, valves can be assesed
b. Exercise ECG/ pharmacological stress ECG
i. Look for inducible ischaemia

Complications

1. Heart failure
2. Myocardial rupture and aneurysmal dilation
3. Ventricular septal defect – high mortality
4. Mitral regurgitation – common valvular defect ollowing MI due infarction of papillary
muscles
5. Cardiac arrhythmias
a. VT- common
b. Bradyarrhythmia : can be treated initially with atropine 0.5 mg i.v. repeated up to
six times in 4 h. Temporary transcutaneous or transvenous pacemaker insertion may
be necessary in patients with symptomatic heart block.
c. Atrial fibrillation: occurs frequently, and treatment with beta-blockers and digoxin
may be required. Cardioversion is possible but relapse is common.
6. Conduction disturbances
a. AV block may occur during acute MI, especially of the inferior wall ( right coronary
artery is involved)
b. treatment with atropine or a temporary pacemaker.
7. Dressler syndrome- post mi pericarditis with or without effusion

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Cardiac arrhythmias

 Manifestations:- sudden death, syncope, heart failure, dizziness, palpitations, asymptomatic

 Bradycardia= HR below 60 during the day or below 50 during the night.
 Tachycardia= HR above 100bpm.
 2 types of tachycardias
o 1. Supraventricular (from atria or AV node)
o 2. Ventricular
 Arrhythmias can arise from normal or diseased tissue( ex:- scar)
 The faster and the more sustained, the tachycardia is more symptomatic.
 When arise from diseased tissue- more symptomatic and potentially life threatening.

Sinus node function

 Normal rate of sinus node- 70-100bpm, maintained by a balance between sympathetic

and parasympathetic nervous discharges.
 Sinus rate is slightly faster in women.

Sinus Arrhythmia

 During inspiration parasympathetic tone falls and heart rate increases and vice versa.
 Normal in children and young adults.
 Cause predictable irregularities of the pulse.

Sinus bradycardia

 Normal in athletes due to increased vagal tone.

 Other causes: - May be systemic or cardiac.

Sinus tachycardia

 Causes may be systemic and cardiac.

Mechanisms of arrhythmia production

 Accelerated automaticity- due to increased rate of diastolic depolarization or changing
the threshold potential. Ex- sympathetic stimulation enhances automaticity causing
sinus tachycardia/ escape rhythms/ accelerated AV nodal (junctional) rhythms.
 Triggered activity - Myocardial damage results in 'after depolarizations'(oscillations in
the transmembrane potential at the end of action potential.) These are exaggerated by
pacing, catecholamines, electrolyte disturbances, hypoxia, acidosis and medications
triggering arrhythmia. Ex: - atrial tachycardia due to digoxin toxicity, ventricular
arrhythmia in long QT syndrome.
 Reentry (circus movements) - if interested, read how a re entry circuit is formed from
kumar and clerk. Ex:- majority of regular paroxysmal tachycardias

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Bradycardias and heart blocks
 Due to sinus bradycardia or atrioventricular block.

Sinus bradycardia

 Extrinsic causes: - 1. Hypothermia, hypothyroidism, cholestatic jaundice and raised

intracranial pressure.

2. drugs- beta blockers, digitalis and other antiarrhythmic drugs.

3. Neurally mediated syndromes.

 Intrinsic causes: - acute ischaemia and infarction of the sinus node. ( as a complication
of acute myocardial infarction), chronic degenerative changes; fibrosis of the atrium and
sinus node( sick sinus syndrome)

Manifestations of sick sinus

syndrome
Causes of sick sinus syndrome
 Sinus bradycardia
 Idiopathic fibrosis( mostly)  sinus arrest
 Ischaemic heart disease  Paroxysmal atrial
 Cardiomyopathy tachyarrhythmias(
 Myocarditis tachy- brady
syndrome)

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Neurally mediated syndromes
 Due to Bezold jarisch reflex
 Causes bradycardia and reflex peripheral vasodilation
 Presents as presyncope or syncope

Name Mechanism Clinical features age group

carotid sinus bradycardia, elderly

syndrome syncope
vasovagal increased bradycardia,
syncope( parasympathetic vasodilation,
neurocardiogenic output( in syncope
syncope) response to
various physical
and emotional
situations)

Medications causing syncope

 antihypertensives
 Tricyclic antidepressants
 Neuroleptics

Management
Sinus bradycardia

 Remove the extrinsic causes.

 Temporary pacing in patients with reversible causes until normal sinus rhythm is restored or
in patients with chronic degnerative conditions until a permenant pacemaker is implanted.

Chronic symptomatic sick sinus syndrome

 Permanent pacing + antiarrhythmic drugs/ ablation

 Anticoagulation unless contraindicated( because thromboembolism is common in tachy
brady syndrome)

Carotid sinus hypersensitivity (asystole more than 3s)

 Permanent pacemaker specially if symptoms are produced by carotid sinus massage and life
threatening causes of syncope have been excluded.

Vasovagal attacks

 Avoiding the situations causing them if possible.

 If an attack threatens, sitting/ lying down or applying counter pressure maneuvers(
pushing palms together and crossing legs)

224
  Increased salt intake
 compression of lower legs with a hose
 drugs:- beta blockers, alpha agonists, midodrine, myocardial negative ionotropes( ex:-
dysopyramide)
 Malignwnt neurocardiogenic syncope( syncope associated with injuries and
demonstrated asystole)- permanent pacemaker therapy

Heart Block
First degree AV block

 Simple prolongation of PR interval more than 0.22s

Second degree AV block

 Mobitz type 1 (wenchebach phenomenon) - progressive PR interval prolongation until a P

wave fails to conduct. Generally due to a block in AV node.
 Mobitz type 2- when dropped QRS complex is not preceeded by progressive PR interval
prolongation. Usually QRS complex is wide. Due to a block at infranodal level. Risk of
progression to complete heart block is relatively greater and resultant escape rhythm is less
reliable.
 2:1 or 3:1 block occurs when every second or third p wave conducts to ventricles. this form
is neither Mobitz 1 nor 11
 Acute myocardial infarction can produce second degree heart block.
 Inferior MI- close monitoring and transcutaneous temporary back up pacing is the
treatment.
 Anterior MI- second degree heart block is associated with a high risk to progression to
complete heart block.

Third degree block

 Atrial activity fails to conduct to ventricles.

 Life is maintained by a spontaneous escape rhythm.
 Narrow complex escape rhythm- arise from his bundle( more proximally to AV node)
 Escape rhythm- rate- 50-60bpm, relatively reliable.
 Rx- depends on aetiology. * Recent onset transient causes- IV atropine, but temporary pace
maker facilities should be available. *chronic narrow complex symptomatic AV blocks-
permanent pacing.
 Broad complex escape rhythm- arise more distally in bundle of His. Resultant escape rhythm
is relatively slow and unreliable. Dizziness and blackouts often occur. In elderly- caused by
degenerative fibrosis and calcification. (Levs disease)
In younger- due to an inflammatory process (Lenegre disease)
Other causes- ischaemic heart disease, myocarditis and cardiomyopathy.
Rx- permanent pace maker implantation- pacing considerably reduces moratality.
For those with severe left ventricular dysfunction- implantable cardioverter defibrillator
(to prevent ventricular arrhythmia)

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Bundle branch block

 Bundle branch conduction delay- Slight widening of QRS complex. Known as incomplete
bundle branch block.
 Complete block of a bundle branch - a wider QRS complex.
o RBBB- deep S in lead 1 and v6, tall R in lead 1 and v6 (late activation of right
ventricle)
o LBBB- deep S in lead V1, tall R in lead 1 and 6

Hemiblock

1. Left anterior hemiblock (block of anterior division of left bundle branch) - LV activation from
inferior to superior- hence left axis deviation

2. Block of posterior inferior division - right axis deviation.

Bifascicular block

Combination of block of two of the following: - right bundle branch, left antero superior division, left
postero inferior division of left bundle branch.

Clinical features of heart blocks

Bundle branch blocks- asymptomatic, wide splitting of second heart sound

Intermittent complete heart block or ventricular tachyarrhythmias- syncope

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Aetiology of heart blocks

 RBBB- congenital( VSD, PS and TOF), pulmonary embolism, pulmonary hypertension,

myocardial infarction, fibrosis, Chagas disease
 **** RBBB alone doesn't alter the axis( unless associated right ventricular hypertrophy or
fascicular block)
 RBBB + left axis deviation - ostium primum ASD, diffuse conduction tissue disease affecting
right bundle and left anterior fascicle.
 Complete LBBB- extensive left ventricular disease, aortic stenosis, hypertension, myocardial
infarction and severe coronary disease.

Supraventricular tachycardia
 Arise from atrium or AV junction.
 Normal QRS

Inappropriate sinus tachycardia

 Persistent increase in resting heart rate unrelated to/ out of proportion with the level of
physical or emotional stress.
 Mainly in young women
 Mainly due to secondary causes and rarely due to intrinsic abnormalities of sinus node.
 Acute secondary causes - exercise, emotion, pain, fever, infection, acute heart failure, acute
pulmonary embolism, hypovolemia
 Chronic causes- pregnancy, anaemia, hyperthyroidism, catecholamine excess
 Rx- treating the underlying cause, beta blockers, ivabradine( pacemaker current blocker)-
when beta blockade is not tolerated

AV junctional tachyarrhythmias

 AVnRT and AVRT are known as paroxysmal SVTs( supraventricular tachycardia)

 Often in young patients with no or little structural heart disease.
 First presentation - between 12-30 years if age.
 Prevalence- 2.5/1000

AVNRT (AV nodal reentrant tachycardia)

 Twice common in women

 Often starts suddenly without provocation.
 Aggravating/inducing factors- exertion, emotional stress , coffee, tea, alcohol
 Spontaneously stop/ continue until medical intervention
 Pathophysiology: - two different pathways in AV node.
1. Slow conduction and short effective refractory period
2. Fast conduction and long effective refractory period
* In sinus rhythm, impulses are conducted through fast pathway.
If an atrial impulse occurs when the fast pathway is still refractory- slow pathway takes over
and the impulse travels back in fast pathway, giving rise to slow- fast( typical AVNRT)
* Rarely- fast-slow or long RP tachycardia

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ECG features

 Usual rate- 140-240 bpm

 Normal QRS, sometimes show typical bundle branch block
 P waves- not visible or seen immediately before or after QRS complex.

AVRT (atrioventricular reentrant tachycardia)

 It is a large circuit as depicted below.

 It is a macro circuit.

 Each part of the re entry circuit is activated sequentially (one after the other) - therefore
atria are activated after ventricles- thus p waves are seen between QRS and T waves.

228
 Interesting facts about accessory pathways.

 Most commonly found on left side.

 Can occur anywhere around AV groove

 Commonest accessory pathways; Kent

bundles- found in free wall or septum.

 Mahaim fibres- atriofascicular or

nodofascicular fibres close to right bundle
branch.

A thing to understand

If the accessory pathway conducts only from ventricles- to atria, since it doesn't happen
during sinus rhythm, it is not visible on surface ECG during the sinus rhythm.

If it conducts from atria to ventricles during the sinus rhythm, it is depicted on ECG.
The ECG findings- short PR interval (because, the accessory pathway conducts quickly,
delta wave (early slurred part of QRS complex due to preexcitation).
Wolff- parkinson- white syndrome = palpitations+ pre excited ECG

Antidromic AVRT

 Occurs when ventricles are activated via accessory pathway and the atria are activated in a
retrograde manner through AV node.
 This results in broad complex tachycardia
 More prone to atrial fibrillation. If AF occurs, it produces irregularly irregular broad complex
tachycardia.
 If the accessory pathway has short antegrade effective refractory period, the impulse is
conducted to ventricles very fast and it causes ventricular fibrillation.
 It may result in sudden death which might be the first manifestation of WPW syndrome in
young patients.
 Verapamil and digoxin can precipitate ventricular fibrillation. Thus they should never be
used to treat AF in WPW syndrome.

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Clinical features of AVRT and AVNRT
 Leading symptoms of SVT- rapid regular palpitations( terminated by valsalva maneuver),
irregular palpitations ( due to atrial premature beats, atrial flutter with varying AV
conduction block, atrial fibrillation, multivocal atrial tachycardia)
 Other symptoms - anxiety, dizziness, dyspnoea, palpitations, neck pulsation, central chest
pain, syncope (10-15%)
 Polyuria- increased release of atrial natriuretic peptide during tachycardia.
 Sign- rapid heart rate( may be the only pathological finding in in younger individuals with no
structural heart disease.
 Prominent JVP due to atrial congestion against closed AV valves.
 Uncontrolled AF- reduce cardiac output - hypotension and congestive cardiac failure.

Management of AVNRT and AVRT

In an emergency, no need to distinguish between AVRT and AVNRT because both are given the same
treatment.

 SVT + haemodynamic instability----> emergency cardioversion

 SVT with haemodynamic stability -------> vagal maneuvers ( right carotid massage,
valsalva maneuver, facial immersion in cold water)
 If not successful - IV adenosine 6 mg IV push (followed by 12mg if needed)

Adenosine- half life is 10 seconds, transiently blocks AV conduction terminating supraventricular

tachycardia.

Side effects of adenosine

o Chest pain
o Impending doom
o Bronchospasm
o Flushing
o Heaviness of limbs.

Alternatives to adenosine
Caution to use
Verapamil 5-10 mg IV over 5-10 min
Adenosine,
Or
Bronchial asthma
Beta blocker

(Esmolol, propanolol, metoprolol)

******Don't give verapamil after beta blockers orif tachycardia is a broad complex tachycardia.
**********

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Long term management
 Refer to cardiologist/ electrophysiologist
 Non pharmacological - ablation of accessory pathway( in AVRT- ablation of accessory pathway,
in AVNRT- modification of slow pathway in AV node: 1% risk of AV block)
 Pharmacological - verapamil, diltiazem, beta blockers( proven efficacy in 60-80%), sodium
channel blockers ( flecainaide, propafenone), potassium repolarization current blockers(
sotalol, dofetilide, azimilide) , multichannel blocker( amiodarone)

Atrial arrhythmias
 Ex:- atrial fibrillation, atrial flutter, atrial tachycardia, atrial ectopic beats
 Aetiology: - increased age, MI, hypertension, obesity, diabetes mellitus, hypertrophic
cardiomyopathy, heart failure, valvular heart disease, myocarditis, pericarditis,
cardiothoracic surgery, electrolyte imbalance, alcohol use, obstructive airway disease, chest
infections and hyperthyroidism.

Atrial fibrillation
 1-2% in general population
 Pathophysiology - any condition causing raised atrial pressure, increased atrial muscle mass,
atrial fibrosis, inflammation or infiltration can predispose atrial fibrillation

Causes of AF

o Rheumatic heart disease

o Alcohol intoxication
o Thyrotoxicosis
o Hypertension
o Heart failure
o Cardiac surgery

****** Thyroid function tests is a must in patients with atrial fibrillation*********

**Lone/ idiopathic atrial fibrillation - no identified cause. A genetic predisposition may be
there*****

Rate of AF- 300-600 bpm, ventricular rate- 120-180 bpm

Automatic foci- predominantly located in pulmonary veins.

231
o
Clinical features -

Symptoms - incidental finding (30%), rapid palpitations, dspnoea, chest pain, reduced
exercise capacity (MCQ point)
Signs- irregularly irregular pulse
ECG- fine oscillations of baseline (fibrillation waves), no p waves, irregularly irregular QRS
complexes

Clinical classification

First detected- irrespective of duration of severity of symptoms

Paroxysmal - stops spontaneously within 7 days
Persistent - continuous for more than 7d
Longstanding persistent - continuous for more than 1 year
Permanent - continuous, with a joint decision between patient and the physician to cease
further attempts to regain sinus rhythm.

Management of AF

Acute management
 Treating the provoking cause
 Ventricular rate control - by AV blocking drugs
 Cardioversion - electrically by DC shock/ medically by IV antiarrhythmic drugs
(flecainaide/ vernakalant/ propafenone/ amiodarone)/ oral antiarrhythmic drugs
(flecainaide or propafenone); pill in pocket approach.
 For cardioversion, biphasic defibrillation is more effective than monophasic defibrillation
 Patients are full anticoagulated with warfarin (INR 2-3) or a direct acting oral
anticoagulant for 3 weeks before cardioversion and at least 4 weeks after the procedure.
 If atrial fibrillation is less than 48 hours, anticoagulation is not necessary.
 If cardioversion is urgent and patient is not on anticoagulation, transoesophageal echo is
done to exclude the atrial thrombus.

Long-term management

 Two strategies
 1. Rate control ( AV nodal slowing agents plus oral anticoagulation)
 2. Rhythm control( antiarrhythmic drugs plus DC cardioversion plus oral anticoagulation)

MCQ point

No net mortality or symptoms benefit to be gained

from one strategy compared with the other
according to AFFIRM and AF-CHF trials.

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Rhythm control

 Better for younger, symptomatic physically active patients.

 Medications: - 1. Patients with no significant heart disease- class IA, IC, or III
antiarrhythmic drugs. (But amiodarone should be reserved until other drugs have failed).
2. Patients with heart failure or left ventricular hypertrophy - only
amiodarone
3. Patients with coronary artery disease- sotalol or amiodarone
4. Paroxysmal AF or early persistent atrial fibrillation - left atrial ablation
*******Ablation is more effective than antiarrhythmic drugs. May completely
cure********
********Ablation doesn't improve long term cardiovascular outcome*********
Complications of ablation - stroke, bleeding, recurrence.

Rate control

 Primary method for those who are more than 65 yrs of age with recurrent atrial
tachyarrhythmias/ symptomatic and symptoms are relieved by slowing the heart
rate
 Persistent tachyarrhythmias and have failed cardioversion/ serial antiarrhythmic
drugs therapy
 Increased risk of using a particular antiarrhythmic agent.

Medications: - digoxin, beta blockers, non dihydropyridine calcium channel blockers (verapamil,
diltiazem)

Elderly, non ambulant- digoxin monotherapy is sufficient

Younger- digoxin + additional agents (because catecholamines easily overwhelm vagotonic effect of
digoxin)

Older patients with poor rate control despite optimal medical therapy- AV node ablation and
pacemaker implantation. (Ablate and pace strategy)+ Lifelong anticoagulation

233
Anticoagulation

 To determine the need for anticoagulation - CHA2DS2VASc score

 To balance the long term anticoagulant prophylaxis against the risk of haemorrhage- HAS-
BLED score.

234
Atrial flutter
 Atrial rate- 250-300, usual ventricular rate- 150bpm
 Due to a macro reentrant circuit in atria tricuspid annulus.
 Most frequent pattern- counter clockwise flutter
 Clockwise (reverse) flutter is also there, but uncommon.
 ECG- regular sawtooth like flutter waves. Counterclockwise pattern- flutter waves are
negative in inferior leads and positive in lead V1 and 2

Management

 Symptomatic and acute- cardioversion

 Those who have had flutter for more than 1-2 days- treated similarly to atrial fibrillation
 Acute pharmacological cardioversion- by class If or certain class III antiarrhythmic drugs.
 Recurrent paroxysms- class III antiarrhythmic drugs, AV node blockers( to reduce rate)
 Recurrent atrial flutter- treatment of choice is catheter ablation.

Atrial tachycardia

 Less common.
 Usually associated with structural heart disease or idiopathic

235
  Atrial tachycardia with block - often a result of digitalis poisoning.
 Rate of reentrant tachycardia- 125-150 bpm, regular PP interval
 Automatic tachycardia, rate- 125-250 bpm
 Automatic atrial tachycardia has a warm up effect (gradually increasing rate at the
beginning) and cool down effect (gradually decreasing rate near termination.
 Automatic atrial tachycardia may lead to tachycardia induced cardiomyopathy
 Management options: - cardioversion, antiarrhythmic drugs therapy, AV nodal slowing
agents. Radio frequency catheter ablation.

Atrial ectopic beats

 Often no symptoms
 ECG- early and abnormal p waves
 Management - only if symptomatic, beta blockers

Ventricular tachyarrhythmias
Sustained ventricular tachycardia

 Symptoms - presyncope,syncope hypotension, cardiac arrest

 Rate-120-220
 Signs- canon a waves inneck, variable intensity of first heart sound.
 ECG- broad QRS, capture beats( intermittent narrow QRS), fusion beats
 SVT with bundle branch block may resemble ventricular tachycardia
 Management - haemodynamic instability- cardioversion, if stable- IV beta blockers/ class I
drugs/amiodarone

Ventricular fibrillation

 Pulse less, becomes unconscious, respiration stops( cardiorespiratory arrest)

 ECG- shapeless rapid oscillations
 Usually provoked by a ventricular ectopic
 Aetiology - MI, electrolyte imbalance

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  Rarely reverses spontaneously
 Only effective treatment - electrical defibrillation
 Survivors without an identifiable reversible cause- high risk of sudden death. Hence
implantablecardioverter defibrillator is the first line therapy.

Brugada syndrome

 An inheritable condition
 Cause idiopathic ventricular defibrillation
 Common in young male adults in south east Asia
 Diagnosis - by classic ECG changes/ provoking by administration of class I antiarrhythmic
drugs
 ECG- right bundle branch block with coved ST elevation.
 Symptoms/ presentation - sudden death during sleep, resuscitated cardiac arrest, syncope
 Management - ICD( beta blockers - no use, might be harmful)

Long QT syndrome

 Ventricular repolarization is prolonged.

 Congenital long QT syndrome - two syndromes- jervell- Lange- Nielson syndrome (
associated with congenital deafness), Romando- Ward syndrome ( no congenital deafness)
 Read molecular biology of congenital long QT syndrome from Kumar and Clerk if you are
interested.
 Acquired long QT syndrome - QT prolongation and tosardes de pointes usually provoked by
bradycardia
 Clinical features - syncope, palpitations, sudden death( due to VF)
 Management -
 Acute- correct electrolyte disturbances, stop causative drugs, maintain heart rate with atrial
or ventricular pacing, magnesium sulphate, IV isoprenaline( for acuired only, contraindicated
in congenital long QT syndrome)
 Long term management - congenital - beta blockers/ pacemaker therapy, left cardiac
sympathetic denervation, ICD

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Short QT syndrome

 Five types
 Due to genetic defects
 Faster repolarization of ventricles
 Causes ventricular tachyarrhythmias, sudden death
 Treatment - ICD

Normal heart ventricular tachycardia

 Monomorphic ventricular tachycardia in patients with structurally normal hearts( idiopathic

ventricular tachycardia)
 Benign, excellent long term prognosis
 Occasionally, incessant( Gallarvadian tachycardia)
 If untreated- leads to cardiomyopathy

Non-sustained ventricular tachycardia

 Definition- ventricular tachycardia that is five consequetive beats or more but lasts for less
than 30 seconds
 Usually no treatment is required.

Ventricular ectopics

 Symptoms - extra beats, missed beats, heavy beats

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 Signs- irregular pulse, pulses bigeminus( when premature beats occur regularly after every
normal beat)
 Management - beta blockers if highly symptomatic, catheter ablation if arise from a single
focus
 ECG- ectopic QRS complex is abnormal and broad

Long term management options of cardiac

tachyarrhythmias

o Antiarrhythmic drugs therapy

o Ablation therapy
o Device therapy.

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240
Infective endocarditis

Infective endocarditis is an endovascular infection of cardiovascular structures, including cardiac

valves, atrial and ventricular endocardium, large intrathoracic vessels and intracardiac foreign
bodies, such as prosthetic valves, pacemaker leads and surgical conduits.

Aetiology
Endocarditis is usually the consequence of two factors: the presence of organisms in the
bloodstream, and abnormal cardiac endothelium that facilitates their adherence and growth.

Bacteraemia may arise for patient-specific reasons (poor dental hygiene, intravenous drug use, soft
tissue infections) or may be associated with diagnostic or therapeutic procedures (dental treatment,
intravascular cannulae, cardiac surgery or permanent pacemakers).

Damaged endocardium promotes platelet and fibrin deposition, which allows organisms to adhere
and grow, leading to an infected vegetation. Valvar lesions may create non-laminar flow, and jet
lesions from septal defects or a patent ductus arteriosus result in abnormal vascular endothelium.
Aortic and mitral valves are most commonly involved in infective endocarditis; intravenous drug
users are the exception; as right-sided lesions are more common in these patients.

Organisms:

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Diagnosing criteria:

Clinical features
The clinical presentation of infective endocarditis is dependent on the organism and the presence of
predisposing
Cardiac conditions. Infective endocarditis may occur as an acute, fulminating infection but also as a
chronic or subacute illness with low-grade fever and non-specific symptoms

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Investigations
The mainstays of diagnosis of infective endocarditis are blood cultures and echocardiography,
performed in order to
Identify the organism, ensure appropriate therapy and monitor the patient’s response to therapy
(Box 30.47). Echocardiography is an extremely useful tool if used appropriately but is not an
appropriate screening test for patients with just a fever or an isolated positive blood culture where
there is a low pre-test probability of endocarditis. A negative echocardiogram does not exclude a
diagnosis of endocarditis and TOE and CT-PET may be required, particularly in cases of suspected
prosthetic valve infection.

Management

The location of the infection means that prolonged courses of antibiotics are usually required. The
combination of antibiotics may be synergistic in eradicating microbial infection and minimizing
resistance.Blood cultures should be taken prior to empirical antibiotic therapy (but this should not
delay therapy in unstable patients).Antibiotic treatment should continue for 4–6 weeks. Typical
therapeutic regimens are shown in Box 30.48 but advice on specific therapy should be sought from
the local microbiology department, according to the organism identified and current sensitivities.

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Prevention
Three groups of patients who could be considered at highest risk of developing infective
endocarditis and who suffered significant morbidity and mortality complications from it:

• Those who have prosthetic valves (including transcatheter devices) or material used for
valve repair
• Those with a previous episode of IE
• Those with uncorrected cyanotic congenital heart disease or who have received palliative
shunts. Patients who have successful corrective surgery are at high risk for the first 6 months
postoperatively.
The ESC recommends that these groups should receive antibiotic prophylaxis during high-risk
procedures. This includes dental procedures that involve manipulation of the gingival or periapical
part of the teeth or perforation of the oral mucosa. (The American Heart Association also considers
that cardiac transplant patients with valvular heart disease should be included as highest-risk
patients.)
The ESC also provided additional recommendations applicable to all patients with valvular heart
disease (including the highest-risk patients). These include:
• Regular dental check-ups (6 months for the highest-risk groups and 12 months for all others)
• Disinfection of wounds and eradication of chronic bacterial carriage (skin, urine)
• Curative antibiotics for any focus of bacterial infection
• No self-medication with antibiotics
• Strict infection control during at-risk procedures

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Valvular disorders

Mitral Valve
Mitral stenosis

Commonly due to rheumatic heart disease following previous rheumatic fever due to infection with
a group A β-haemolytic streptococcus.more common in women than men. Inflammation leads to
commissural fusion and a reduction in mitral valve orifice area, causing the characteristic doming
pattern seen on echocardiography. Over many years the condition progresses to valve thickening,
cusp fusion, calcium deposition, a severely narrowed (stenotic) valve orifice and progressive
immobility of the valve cusps.Other causes of mitral stenosis include:
Congenital mitral stenosis, mitral annular calcification, rarely.

Symptoms
Usually, there are no symptoms until the valve orifice is moderately stenosed (area <2 cm2).
Progressively severe dyspnea develops from the elevation in left atrial pressure, vascular congestion
and interstitial pulmonary oedema. A cough productive of blood-tinged, frothy sputum or frank
hemoptysis may occur. The development of pulmonary hypertension eventually leads to right heart
failure and its symptoms of weakness, fatigue and abdominal or lower limb swelling. The large left
atrium predisposes to atrial fibrillation, giving rise to symptoms such as palpitations. Atrial
fibrillation may result in systemic emboli, most commonly to the cerebral vessels, producing
neurological sequelae, but mesenteric, renal and peripheral emboli are also seen.

Signs

Face - mitral facies or malar flush. This is a bilateral, cyanotic or dusky pink discoloration
over the upper cheeks, which is due to arteriovenous anastomoses and vascular stasis.
Pulse – Small volume, irregularly irregular if Atrial Fib present in later cases.

JVP – “a” wave if pulmonary hypertension or tricuspid stenosis present

Palpation – Tapping apex,

Auscultation – Loud first heart sound(not in mitral valve calcification).Opening snap will be
present.followed by low pitched,rumbling,mid-diastolic murmur,best heard with the bell,at
the apex and the patient lying on the left lateral in expiration.

Investigations

CXR - left atrial enlargement with straightening of the left heart border and a ‘double
shadow’ on the border of the right and left atria.Pulmonary vascular congestion and
enlargement of the main pulmonary arteries may also be apparent in severe disease.

ECG -In sinus rhythm the ECG may show a bifid P wave owing to delayed left atrial activation.
However, atrial fibrillation is frequently present.

Echo -left atrial size and the degree of thickening, calcification and mobility of the mitral
leaflets, as well as thedegree of commissural fusion

Cardiac catheterization -Left and right heart catheterization may be required in patients
with severe mitral stenosis referred for intervention.

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Management

Early mild dyspnoea, can usually be treated with low doses of diuretics. The onset of atrial fibrillation
requires treatment with beta-blockers or DC cardioversion and anticoagulation to prevent atrial
thrombus and systemic embolization. Patients with severe mitral stenosis who develop persistent
symptoms or pulmonary hypertension are appropriate for intervention.
There are four operative measures.

Trans-septal balloon valvotomy

A catheter is introduced into the right atrium via the femoral vein under local anaesthesia in the
cardiac catheter laboratory. The interatrial septum is then punctured and the catheter advanced into
the left atrium and across the mitral valve. A balloon is passed over the catheter to lie across the
valve and then inflated briefly to split the valve commissures.

Closed valvotomy - This operation is advised for patients with mobile, non-calcified and non-
regurgitant mitral valves. The fused cusps are forced apart by a dilator introduced through the apex
Open valvotomy - This operation is often preferred to closed valvotomy. The cusps are carefully
dissected apart under direct vision. Cardiopulmonary bypass is required. Open dissection reduces
the likelihood of causing traumatic mitral regurgitation.
Mitral valve replacement
Replacement of the mitral valve is necessary if:
• Mitral regurgitation is also present
• There is a badly diseased or calcified stenotic valve that cannot be re-opened without
producing significant regurgitation
• There is severe mitral stenosis and thrombus in the left atrium despite anticoagulation.
Artificial valves may work successfully for more than 20 years. Anticoagulants are generally
necessary to prevent the formation of thrombus, which might obstruct the valve or embolize.

Mitral regurgitation
Mitral regurgitation can occur due to abnormalities of the valve leaflets, the annulus, the chordae
tendineae or papillary muscles, or the left ventricle. The most frequent causes of mitral regurgitation
are degenerative (myxomatous) disease, ischaemic heart disease, rheumatic heart disease and
infectious endocarditis. Mitral regurgitation is also seen in diseases of the myocardium (dilated and
hypertrophic cardiomyopathy), rheumatic autoimmune diseases(e.g. systemic lupus erythematosus),
collagen diseases (e.g.Marfan’s and Ehlers–Danlos syndromes) and disorders caused by drugs,
including centrally acting appetite suppressants (fenfluramine) and dopamine agonists (cabergoline).

Symptoms
Mitral regurgitation can be present for many years and the cardiac dimensions greatly increased
before any symptoms occur.
• Dyspnoea and orthopnoea develop because of pulmonary venous hypertension that arises as a
direct result of the mitral regurgitation and secondarily as a consequence of left ventricular failure.
• Fatigue and lethargy develop because of the reduced cardiac output.

In the late stages of the disease the symptoms of right heart failure also occur and eventually lead
to congestive cardiac failure.

Signs
The physical signs of uncomplicated mitral regurgitation are:
• Laterally displaced (forceful) diffuse apex beat and a systolic thrill (if severe).

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• Soft first heart sound, owing to the incomplete apposition of the valve cusps and their partial
closure by the time ventricular systole begins.
• Pansystolic murmur, due to the occurrence of regurgitation throughout the whole of systole, being
loudest at the apex but radiating widely over the precordium and into the axilla.
• Mid-systolic click, which may be present with a floppy mitral valve (see later); it is produced by the
sudden prolapse of the valve and the tensing of the chordae tendineae that occurs during systole.
This may be followed by a late systolic murmur owing to some regurgitation.
• Prominent third heart sound (S3), owing to the sudden rush of blood back into the dilated left
ventricle in early diastole

Investigations
Chest X-ray - The chest X-ray may show left atrial and left ventricular enlargement.There is an
increase in the cardiothoracic ratio and valve calcification may be present.
ECG-The ECG shows the features of left atrial delay (bifid P waves) and left ventricular hypertrophy,
as manifested by tall R waves in the left lateral leads
Echocardiogram - The echocardiogram shows a dilated left atrium and left ventricle. TOE can be
helpful to identify structural valve abnormalities before surgery and intraoperative TOE can aid
assessment of the efficacy of valve repair.
Cardiac catheterization - Left and right heart catheterization is appropriate for patients referred for
surgical repair or replacement.

Management
Mild to moderate mitral regurgitation can be managed conservatively by following the patient with
serial echocardiograms. Prophylaxis against endocarditis is needed. Current ESC guidelines
recommend surgical intervention in patients with symptomatic severe mitral regurgitation, LVEF of
more than 30% and end-diastolic dimension of less than 55 mm, and in asymptomatic patients with
left ventricular dysfunction
Surgery should also be considered in patients with asymptomatic severe mitral regurgitation with
preserved left ventricular function and atrial fibrillation and/or pulmonary hypertension.

Aortic Valve

Aortic stenosis
Is a chronic progressive disease that limits left ventricular outflow, leading to symptoms of chest
pain, breathlessness, syncope and pre-syncope, and fatigue. Aortic valve stenosis includes calcific
stenosis of a trileaflet aortic valve, stenosis of a congenitally bicuspid valve and rheumatic aortic
stenosis.
Calcific aortic valvular disease (CAVD) is the most common cause of aortic stenosis and occurs
mainly in the elderly.Risk factors for CAVD include old age, male,sex, elevated lipoprotein and LDL
cholesterol, hypertension, diabetes and smoking.
Bicuspid aortic valve (BAV) is the most common form of congenital heart disease, occurring in 1–
2% of live births; in about 9% of cases it is familial. Patients with familial bicuspid valve tend to
present at an earlier age. BAV is associated with aortic coarctation, root dilation and, potentially,
aortic dissection, and patients should have regular follow-up echocardiography.
Rheumatic fever can produce progressive fusion, thickening and calcification of the aortic valve. In
rheumatic heart disease, the aortic valve is affected in about 30–40% of cases and there is usually
associated mitral valve disease.
Other causes of valvular stenosis include chronic kidney disease, Paget’s disease of bone, previous
radiation exposure and systemic lupus erythematosus

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Symptoms
There are usually no symptoms until aortic stenosis is moderately severe (when the aortic orifice is
reduced to one-third of its normal size). At this stage, exercise-induced syncope, angina and dyspnea
develop. When symptoms occur, the prognosis is poor: on average, death occurs within 2–3 years if
there has been no surgical intervention.

Signs
Pulse – Slow rising, low volume, in sinus rhythm
Aortic area – Systolic thrill
Apex – Not displaced, Sustained
Sounds – Ejection click, Soft A2, S4
Murmurs – Ejection Systolic, low pitched, Radiating to carotids

Other findings include:

• Systolic ejection click, unless the valve has become immobile and calcified
• Soft or inaudible aortic second heart sound when the aortic valve becomes immobile
• reversed splitting of the second heart sound (splitting on expiration)
• Prominent fourth heart sound, caused by atrial contraction and heard unless coexisting mitral
stenosis prevents this.

Investigations
CXR - a relatively small heart with a prominent, dilated, ascending aorta. This occurs because
turbulent blood flow above the stenosed aortic valve produces so-called ‘post-stenotic dilation’.
ECG -The ECG shows left ventricular hypertrophy. A left ventricular ‘strain’ pattern due to ‘pressure
overload’ Echocardiogram - Echocardiography readily demonstrates the thickened, calcified and
immobile aortic valve cusps, and the presence of left ventricular hypertrophy; it can be used to
determine the severity of aortic stenosis. TOE is rarely indicated.
Cardiac catheterization - Cardiac catheterization is rarely necessary since all of this information
Coronary angiography is required before surgery is recommended.
CMR and cardiac CT - These techniques are indicated for assessing the thoracic aorta for the
presence of aneurysm, dissection or coarctation but are rarely needed.

Management
In patients with aortic stenosis, symptoms are a good index of severity and all symptomatic,
appropriate patients should have aortic valve replacement. Patients with a BAV and ascending aorta
of over 50 mm or expanding at more than 5 mm per year should be considered for surgical
intervention. Asymptomatic patients should be under regular review for assessment of symptoms
and echocardiography.
Surgical intervention for asymptomatic people with severe aortic stenosis is recommended in those
with:
• Symptoms or hypotension during an exercise test
• An LVEF of less than 50%
• Moderate to severe stenosis undergoing CABG, surgery of the ascending aorta or other
cardiac valve.
– Peak velocity through the aortic valve >5.5 m/s
– Systolic pulmonary artery pressure >60 mmHg
– Rapid increase in velocity through the valve at >0.3 m/s/year
Antibiotic prophylaxis against infective endocarditis is recommended.Provided that the valve is not
severely deformed or heavily calcified, critical aortic stenosis in childhood or adolescence can be
treated by valvotomy (performed under direct vision by the surgeon or by balloon dilation using X-
ray visualization).

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This produces temporary relief from the obstruction. Aortic valve replacement will usually be
needed a few years later. Balloon dilation (valvuloplasty) has been tried in adults, especially in the
elderly, as an alternative to surgery.
Percutaneous valve replacement
A novel treatment for patients unsuitable for surgical aortic valve replacement is transcatheter
aortic valve implantation (TAVI), with a balloon expandable stent valve. And this technique may
replace the need for surgery.

Aortic regurgitation
Aortic regurgitation can occur in diseases affecting the aortic valve, such as endocarditis, and
diseases affecting the aortic root, such as Marfan’s syndrome

Aortic regurgitation is reflux of blood from the aorta through the aortic valve into the left ventricle
during diastole.

Symptoms
In aortic regurgitation, significant symptoms occur late and do not develop until left ventricular
failure develops. Angina pectoris may arise. Varying grades of dyspnoea occur, depending on the
extent of left ventricular dilation and dysfunction. Arrhythmias are relatively uncommon.

Signs
The signs of aortic regurgitation are many and are due to the hyperdynamic circulation, reflux of
blood into the left ventricle and increased left ventricular size.
The pulse is bounding or collapsing. The following signs, which are rare, also indicate a
hyperdynamic circulation:
• Quincke’s sign – capillary pulsation in the nail beds
• de Musset’s sign – head nodding with each heart beat
• Duroziez’s sign – a to-and- fro murmur heard when the femoral artery is auscultated with pressure
applied distally (if found, it is a sign of severe aortic regurgitation)
• pistol shot femorals – a sharp bang heard on auscultation over the femoral arteries in time with
each heart beat.
The apex beat is displaced laterally and downwards and is forceful in quality. On auscultation, there
is a high-pitched early diastolic murmur best heard at the left sternal edge in the fourth intercostal
space with the patient leaning forwards and the breath held in expiration. Because of the volume
overload there is commonly an ejection systolic flow murmur. The regurgitant jet can impinge on the
anterior mitral valve cusp, causing a mid-diastolic murmur (Austin Flint rumble).

Investigations
Chest X-ray - left ventricular enlargement and, possibly, dilation of the ascending aorta
ECG-The ECG appearances are those of left ventricular hypertrophy due to ‘volume overload’: tall R
waves and deeply inverted T waves in the left-sided chest leads, and deep S waves in the right-sided
leads. Normally, sinus rhythm is present.
Echocardiogram - The echocardiogram demonstrates vigorous cardiac contraction and a dilated left
ventricle. The aortic root may also be enlarged. TOE may provide additional information about the
valves and aortic root.

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Cardiac catheterization - Cardiac catheterization is appropriate for patients requiring valvular
intervention, although CTCA or CT angiography may be an alternative in younger patients.
CMR and cardiac CT - These techniques may be indicated for assessing the thoracic aorta in cases of
aortic dilation or dissection. CMR can be used to quantify regurgitant volume.

Management
The underlying cause of aortic regurgitation (e.g. syphilitic aortitis or infective endocarditis) may
require specific treatment. Patients with acute aortic regurgitation may need treatment with
vasodilators and inotropes. ACE inhibitors are useful in patients with left ventricular dysfunction and
beta-blockers may slow aortic dilation in Marfan’s patients. Because symptoms do not develop until
the myocardium fails and because the myocardium does not recover fully after surgery, operative
valve replacement may be performed before significant symptoms occur.
Aortic surgery is indicated in:
• Acute severe aortic regurgitation, e.g. endocarditis
• Symptomatic patients (dyspnoea, NYHA class II–IV, angina) with chronic severe aortic
regurgitation
• Asymptomatic patients with an LVEF of ≤50%
• Asymptomatic patients with an LVEF of >50% but with a dilated left ventricle (end-diastolic
dimension >70 mm or systolic dimension >50 mm)
• Those undergoing CABG or surgery of the ascending aorta or other cardiac valve.
Both mechanical prostheses and tissue valves are used. Tissue valves are preferred in the elderly and
in cases where anticoagulants must be avoided, but are contraindicated in children and young adults
because of the rapid calcification and degeneration of the valves. Antibiotic prophylaxis against
infective endocarditis is not recommended.

Pericardial disease

 Pericardium consists of an outer fibrous pericardial sac and an inner serous layer
 The normal amount of pericardial fluid is 20–49 mL
 Presentations

• Acute, incessant and chronic pericarditis

• Pericardial effusion and cardiac tamponade
• Constrictive pericarditis

• Pericardial masses

Acute pericarditis

 more common in men, particularly young

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Clinical features
 chest pain - pleuritic, exacerbated by movement and relieved by sitting forwards
 pericardial friction rub
 ECG abnormalities with widespread concave-upwards (saddle-shaped) ST elevation,
reciprocal ST depression in leads AVR and V1, and PR segment depression
 pericardial effusion
Clinical diagnosis of acute pericarditis can be made with two out of four of these features.

Investigations
Inflammatory blood tests (CRP, ESR, white cell count) - to monitor disease resolution.
Cardiac troponin and creatine kinase.
Chest X-ray

Management and treatment

70–90% of cases acute pericarditis is self-limiting
Treated with aspirin 750–1000 mg 3 times daily or ibuprofen 600–800 mg 3 times daily for 1–2
weeks, together with colchicine (0.5 mg twice daily for 3 months

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Incessant or chronic pericarditis

About 20% of cases of acute pericarditis go on to develop idiopathic relapsing pericarditis, which
may be incessant (recurring within 6 weeks) or chronic (lasting >3 months).
The first-line treatment is non-steroidal anti-inflammatory drugs (NSAIDS) or aspirin with colchicine
for up to 6 months

Tuberculous pericarditis

Over 50% of cases in developing countries and over 90% in patients with HIV
Pericardial aspiration is often required to make the diagnosis.
Constrictive pericarditis is a frequent outcome.
Treatment is as for pulmonary tuberculosis with added prednisolone
60 mg daily for 2–6 weeks

Malignant pericarditis

Carcinoma of the bronchus, carcinoma of the breast and Hodgkin’s lymphoma are the most common
causes
A substantial haemorrhagic pericardial effusion is very typical and is due to obstruction of lymphatic
drainage from the heart.
Radiation and therapy for thoracic tumours may cause radiation injury to the pericardium, resulting
in serous or haemorrhagic pericardial effusion and pericardial fibrosis.

Pericardial effusion and cardiac tamponade

When a large volume collects in this space, ventricular filling is compromised, leading to
embarrassment of the circulation.

Clinical features
Symptoms
• Heart sounds are soft and distant.
• Apex beat is commonly obscured.
• A friction rub may be evident due to pericarditis in the early stages,

Signs
• raised JVP with sharp x descent
• Kussmaul’s sign (rise in JVP/increased neck vein distension during inspiration)
• Pulsus paradoxus
• reduced cardiac output.

Investigations
• ECG -low-voltage QRS complexes with sinus tachycardia
• Chest X-ray- large, globular or pear-shaped heart with sharp outlines. The pulmonary veins are not
distended.
• Echocardiography
• Cardiac CT or MRI
• Pericardiocentesis
 Indicated when a tuberculous, malignant or purulent effusion is suspected.
• Pericardial biopsy

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Management
An underlying cause should be sought and treated if possible.
Most resolve spontaneously. However, when the effusion collects rapidly, tamponade may result.
Pericardiocentesis is then indicated to relieve the pressure

Constrictive pericarditis

Here the pericardium becomes inelastic as to interfere with diastolic filling of the heart
Not as immediately life-threatening
Causes- tuberculosis, haemopericardium, bacterial infection rheumatic heart disease, after open
heart surgery, use of dopamine agonists, such as cabergoline and pergolide.
Fully treatable

Clinical features
The symptoms and signs occur due to:
• reduced ventricular filling (similar to cardiac: Kussmaul’s sign, sharp, pulsus paradoxus; different to
tamponade: raised JVP with deep y descent or Friedreich’s sign)
• Systemic venous congestion (ascites, dependent oedema, hepatomegaly and raised JVP)
• Pulmonary venous congestion (dyspnoea, cough, orthopnoea, paroxysmal nocturnal dyspnoea)
• reduced cardiac output (fatigue, hypotension, reflex tachycardia)
• Rapid ventricular filling (a ‘pericardial knock’ is heard in early diastole at the lower left sternal
border)
• Atrial dilation

Investigations
• Chest X-ray -relatively small heart in view of the symptoms of heart failure. Pericardial calcification
may be present in up to 50%
• ECG -low-voltage
• Echocardiography - thickened, calcified pericardium and small ventricular cavities with normal wall
thickness.
• CT and CMR
• Endomyocardial biopsy
• Cardiac catheterization

Management
Complete resection of the pericardium
Early pericardiectomy is suggested in non-tuberculous cases, before severe constriction and
myocardial atrophy have developed.
In cases of tuberculous constriction, the presence of pericardial calcification implies chronic disease

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Myocardial and Endocardial disease

Cardiac tumours

Primary cardiac tumours are rare and three-quartersof these are benign.
Atrial myxomas- most common.

Myocardial disease

That is not due to ischaemic, valvular or hypertensive heart disease, or a known infiltrative,
metabolic/toxic or neuromuscular disorder
May be caused by:
• An acute or chronic inflammatory pathology (myocarditis)
• Idiopathic myocardial disease (cardiomyopathy).

Myocarditis

Causes
 Viruses (enteroviruses, adenoviruses, human herpes virus-6, Epstein–Barr virus,
cytomegalovirus, hepatitis C and parvovirus B19).
 Chagas’ disease, due to Trypanosoma cruzi,
 Toxins (including prescribed drugs), physical agents, hypersensitivity reactions and
autoimmune conditions

Pathology
Acute phase, myocarditic hearts are flabby with focal haemorrhages;
Chronic cases, enlarged and hypertrophied.
Histology -an inflammatory infiltrate is present –lymphocytes predominating with viral causes,
polymorphonuclear cells with bacterial causes, and eosinophils with allergic and hypersensitivity

Clinical features
Myocarditis typically presents in young adult patients.
Presentation may vary from mild fatigue, palpitations, chest pain and dyspnoea through to fulminant
congestive cardiac failure. Physical examination-soft heart sounds, a prominent third sound and
often a tachycardia.
A pericardial friction rub may be heard.

Investigations
• ECG -diffuse ST-and T-wave abnormalities (concave ST elevation) and arrhythmias.
AV block may be seen with Lyme disease, sarcoid, giant-cell myocarditis and Chagas’disease

Management
Resolves within a few weeks in the majority of patients.
Bed rest is recommended in the acute phase of the illness and athletic activities should be avoided
for 6 months.

Giant cell myocarditis

Characterized by the presence of multinucleated giant cells within the myocardium.

The cause is unknown but it may be associated with sarcoidosis, thymomas and autoimmune
disease.

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The disease has a rapidly progressive course and a poor prognosis.
Immunosuppression is recommended.

Chagas’ disease

Chagas’ disease (see p. 568) is caused by the protozoon Trypanosoma cruzi and is endemic in South
America
Acutely, features of myocarditis are present with fever and congestive heart failure.
Chronically, there is progression to a dilated cardiomyopathy with a propensity towards heart block
and ventricular arrhythmias

Heart failure

 Coronary artery disease is the commonest cause of heart failure in western countries.

Pathophysiology

 When efficiency of heart as a pump reduces, many physiological compensatory mechanisms

come into play. But those mechanisms eventually become pathological.

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 There is a detailed account on pathophysiology in Kumar and Clerk as well as in physiology
text books. Refresh your knowledge with them, if necessary.

Clinical syndromes of heart failure

 Acute vs chronic heart failure

 Heart failure with reduced ejection fraction (EF less than 40%)
Causes: - ischaemic heart disease, valvular heart disease, hypertension
 Heart failure with preserved ejection fraction (diastolic heart failure) (EF more than 50%)
Causes: - elderly hypertensive patients, cardiomyopathy (hypertrophic, restrictive,
infiltrative)
 Heart failure with mid range ejection fraction (LVEF between 40-50%)
 Right ventricular systolic dysfunction
Causes: - chronic left heart failure, primary or secondary pulmonary hypertension,
right ventricular infarction, arrhythmogenic right ventricular cardiomyopathy, adult
congenital heart disease

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Clinical features of heart failure

Investigations in heart failure

 Blood tests- full blood count, Serum creatinine, serum electrolyte, liver biochemistry,
cardiac enzymes
 Chest X ray

Cardiomegaly

Pulmonary congestion

Upper lobe diversion

Fluid in fissure

Kerley B lines

257
Diagnosis of heart failure

258
Management of heart failure

 Aimed at symptomatic relief, prevention and control of disease leading to heart failure.

General lifestyle advice

 Education
 Dietary modification- salt and water restriction
 Smoking cessation
 Alcohol in moderate amounts
 Physical activity, exercise training and rehabilitation- 20-
30 min of endurance exercise 5 times per day
 Vaccination- against pneumococcal disease and influenza
 Sexual activity- nitrate and phosphodiesterase 5 inhibitor
should not be taken together since they cause profound
hypotension together.
 Driving- ok, if no distracting symptoms

259
 Monitoring

Multidisciplinary team approach

260
Drug management

261
Non pharmacological management options

 Revascularization
 Cardiac resynchronization therapy ( biventricular pacing)
 Implantable cardioverter defibrillator
 Cardiac transplantation.

Acute heart failure

 Poor prognostic indicators:- high pulmonary capillary wedge pressure, low serum sodium
concentration, increased left ventricular end diastolic dimension

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  Aetiology:- ischaemic heart disease, valvular heart disease, hypertension, acute and chronic
kidney disease, atrial fibrillation

Pathophysiology

Similar to chronic heart failure.

Diagnosis

Management of acute heart failure

For a detailed description, refer to emergency medicine book.

Goals: - symptomatic relief, reducing the length of hospital stay, reducing mortality

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264
Non pharmacological: - mechanical assist device, ventricular assist device.

265
9. Respiratory diseases

Lung function tests

 Spirometry creates flow volume loops

 Flow volume loops – extra thoracic obstruction

o Ex: Tracheal tumor, retrosternal goiter
o Expiration is not a problem (effort dependent)
o But in inspiration, the trachea collapses. And reduces airflow
𝐹𝐸𝑉1
o Usually, 𝐹𝐼𝑉1 > 1
 FEV1 = Forcefully expired volume in 1 second starting from total lung
capacity
 FIV1 = Forcefully inspired volume in 1 second starting from residual volume
o In this case it becomes <1 due to the obstruction

Ventilation and perfusion

266
Respiratory tract infections

Condition Primary Therapy Alternate Therapy Comments

Acute Bronchitis amoxicillin 500mg po doxycycline or co- Antibiotics are
Antibiotics might be 8hourly or amoxiclav or usually not
considered in erythromycin 250- cefuroxime recommended.
 a severe attack on 500mg po 6 hourly or
initial presentation clarithromycin 250- Duration:5 days CRP may be used to
 persistent 500mg po 12hourly guide the antibiotic
symptoms for 5-7 therapy.
days with no Duration: 5 days
evidence of If >100mg/L-
resolving prescribe antibiotics.
 patients with
known If 20-100mg/ L –
cardiopulmonary review the need.
disease
 presence of Avoid doxycycline in
abnormal lung pregnancy and
signs children.

Persistent paroxysmal
cough>14 days - consider
pertussis
Quinolones should
be avoided. Exclude
pulmonary TB if
cough persists> 2
weeks.
erythromycin 500mg azithromycin or co-
po 6 hourly 14 days or trimoxazole
clarithromycin 500mg
po12 hourly 7-10 days

267
Pneumonia
Community acquired Mild amoxicillin 500mg1g erythromycin or CURB 65 score can be
Pneumonia (CURB 65 = 0- po 8 hourly or clarithromycin or used as a severity
1) Out-patient cefuroxime 500mg po doxycycline indicator.
a) No comorbidities 12 hourly Duration: 5-7 days
- Confusion (new
Duration: 5-7 days OR onset)
azithromycin 4 - Urea > 7mmol/l
days (20mg/dl)
- Respiratory Rate >
30/min
- BP (systolic< 90 or
diastolic < 60mmHg)
- Age ≥ 65years

CURB ≥ 1 needs
hospital admission
CURB 4-5 may need
ICU care (

Outpatient settings -
where urea is not
available CRB 65 may
be used.)

Other factors to
consider in
hospitalization co-
morbidities- poorly
controlled DM,COPD,
CRF, underlying
malignancies etc.
b) With comorbidities amoxicillin 1g po 8 cefuroxime +
(alcoholism, COPD, hourly + doxycycline
bronchiectasis, IV drug clarithromycin500mg
users etc.) po12 hourly Minimum duration
of 5 days
or Minimum duration of 5
days
Use of antimicrobials
within previous 3 months

Moderate Pneumonia co-amoxiclav 1.2g IV 8 In immediate Restrict levofloxacin/

(CURB 65 = 2) Patient hourly/ cefuroxime penicillin or moxifloxacin usage as
requires hospitalization 1.5g IV 8 hourly + they are reserved as

268
 clarithromycin 500mg cephalosporin second line anti TB
po12 hourly hypersensitivity drugs.
levofloxacin PO/IV
Severe Pneumonia cefotaxime 1g IV 8 or moxifloxacin IV
hourly/ ceftriaxone 1-
(CURB 65 = 3-5) May need 2g IV daily +
ICU admission clarithromycin 500mg
IV or po12 hourly
For suspected Add vancomycin IV Add teicoplanin
community-acquired
MRSA (CA-MRSA)
pneumonia

Asthma
• Common chronic condition, cause is incompletely understood.
• commonly starts in childhood (between 3 to 5 years)
• classically there are 3 characteristics:
1. airflow limitation: reversible spontaneously or with treatment
2. airway hyper-responsiveness: wide range of stimuli
3. bronchial inflammation: T lymphocytes, mast cells, eosinophils
• in chronic asthma, inflammation may be accompanied by irreversible airflow limitation.

classification
• can be classified according to its trigger factors, age of onset, inflammatory subtypes, or
response to therapy
• many childhood onset asthmatics have a wheezing illness with inhaled allergic triggers and
often accompanied by eczema.
• in some, inhaled allergens are not relevant. this often start in middle age and attacks
triggered by respiratory infections.
• non atopic individuals may develop asthma in middle age from extrinsic causes: Beta
blockers, NSAIDs.

other clinical phenotypes: brittle asthma, steroid resistance asthma

aetiology
• atopy and allergy:
• "atopy":
• describe a group of disorders, including asthma, hay fever.
• appeared to run in families
• positive skin prick tests to common inhalant allergens
• have circulating allergen specific antibodies.
• elevated serum IgE levels are linked to airway hyperresponsiveness
• genetic factors:
• no single gene for asthma but several, in combination with environmental factors
• environmental factors:
• early childhood exposures to allergens and maternal smoking: influence in IgE production

269
• hygiene hypothesis: growing up in a relatively "clean" environment may predispose to an IgE
response to allergens and vice versa

precipitating factors:
• occupational sensitizers:

• Non-specific factors
• cold dry air inhalation,
• exercise: typically, not while exercising but afterwards
• atmospheric pollution and irritant dusts, vapours, and fumes: tobacco smoke, car fumes,
solvents, strong perfumes.
• diet: increased intake of fresh vegetables and fruit shown to be protective.
• emotion: influence both acutely and chronically
• drugs:
• NASIDs such as aspirin, indomethacin, and ibuprofen
• Beta blockers: nonselective beta blockers but selective beta1 blockers (atenolol) may induce
attacks.

clinical features:
• principal symptoms:
• wheezing attacks

270
 • episodic shortness of breath
• usually worst during night (predominate feature in children)
• precipitate by wide range of triggers

investigations
• Lung function tests:
• PEFR: diurnal variation of this is a good measure of asthma activity, help in the long-term
assessment of disease and response to treatment.
• spirometry: useful specially in assessing reversibility.
• asthma can be diagnosed by demonstrating a >15% improvement in FEV1 or PEFR
following a bronchodilator inhalation.
• carbon monoxide transfer test is normal in asthma.
• Histamine and methacholine bronchial provocation test
• Trial of corticosteroids
• all patients present with severe airflow limitation should undergo this.
• Prednisolone 30mg orally, daily for 2 weeks and lung function measured before and
immediately after the course.
• improvement of FEV1 (>15%) confirms the presence of a reversible elements and should be
replaced with inhaled corticosteroids.
• exhaled nitric oxide: assess the efficacy of corticosteroids
• blood and sputum tests: asthma patients sometimes have an increased eosinophils in
peripheral blood, but sputum eosinophilia is more specific diagnostic finding.
• chest Xray:
• no diagnostic features of asthma.
• overinflation is characteristic during acute episode or chronic severe disease.
• helpful to exclude pneumothorax which occur as a complication of asthma.
• skin tests: skin prick tests should be performed in all cases of asthma to identify allergic
trigger factors.
• allergen provocation tests: useful research tool, important in occupational asthma
investigations but not in ordinary asthma.

management
• involves:
• patient and family education
• patient and family participation in treatment
• avoidance of identified causes where possible
• use lowest effective doses of convenient medications
• control extrinsic factors: active and passive smoking, beta blockers (either tablet or eye
drop), NASIDs
• drug treatment:
• mainstay: inhaled therapeutic agents as aerosols or powders directly into the lungs.
• advantages: avoid of first pass metabolism in liver thus needing lower doses and minimizing
systemic unwanted effects.
• all guidelines published treatments based on three principles:
1. should be self-managed with regular monitoring using PEFR meter and and individual
treatment plan.
2. since asthma is an inflammatory disease, anti-inflammatory therapy (controller) should be
started, even in mild cases.
3. short acting inhaled bronchodilators should be used only to relieve breakthrough symptoms.
• Increases use of bronchodilator treatment to relieve increasing symptoms is an
indication of deteriorating disease.

271
 • Antibiotics: during exacerbations, yellow or green sputum containing eosinophils and
bronchial epithelial cells may be coughed up and this is usually due to viral rather than
bacterial infection and antibiotics are not required.
• mixed evidence for azithromycin as it has both anti-inflammatory and antibacterial
actions.
• Bronchial thermoplasty: novel approach for moderate to severe asthma.

asthma attacks:
• may occur spontaneously but commonly caused by lack of treatment adherence, respiratory
viral infections, allergen exposure or triggering drugs
• their regular treatment should be increased and prednisolone 30 to 60mg should be given
for 2 weeks which can be stopped abruptly without tailing down followed by substitution
with an inhaled corticosteroid preparation.

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COPD
 Definition: a disease state characterized by airflow limitation that is not fully reversible. The
airflow limitation is usually both progressive and associated with an abnormal inflammatory
response of the lungs to noxious particles or gases
 Includes airflow limitation, destruction of lung parenchyma
 Causes hyperinflation of lungs, ventilation/perfusion mismatch, increased work of breathing
and restlessness
 Co-morbidities : IHD, Hypertension, DM, Heart failure, Lung CA,
 <COPD associated systemic diseases>


 Pathological changes
o emphysema and small airways disease + increased mucus-producing goblet cells in
the bronchial mucosa causing chronic bronchitis
o Both cause airflow limitation
o Chronic inflammation mediated by neutrophils, CD8 lymphocytes and macrophages
is there
o It causes small airway fibrosis, alveolar wall destruction
 Emphysema
o defined as abnormal and permanent enlargement of air spaces distal to the terminal
bronchiole, accompanied by destruction of their walls
o 3 Types
 Centri acinar : commonest
 Pan acinar : Seen in alpha 1 antitrypsin deficiency
 Irregular :
 Pathogenesis of COPD
o Cigarette smoking
o Infections cause acute exacerbations
 Need influenza and pneumococcal vaccines
o Alpha 1 anti trypsin deficiency
 Clinical features
o Productive cough with white or clear sputum
o Wheezing and breathless
o Recurrent LRTI

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 o Systemic effects
 Hypertension, osteoporosis, depression, weight loss, reduced muscle mass,
general weakness, right heart failure
o If cyanosed they are CO2 insensitive
 Also oedematous, peripheral vasodilation, bounding pulse, coarse flapping
tremors
 Papilledema

o Remember to mention this in your cases

 May have respiratory failure, pulmonary hypertension, cor pulmonale
 Investigations
o Lung functions : FEV1:FVC ratio reduced, - Partially reversible (change <15%). PEFR
low. Normal or increased lung volumes. Low CO2 transfer factor if severe
emphysema
o CXR : Normal or Hyperinflation, flat diaphrams, large bullae, pruned blood vessels
(low peripheral blood vessels), large proximal vessels
o HRCT
o ↑Hb ↑PCV : secondary polycythemia
o Blood gases
o Sputum Ex : In infective exacerbations. (may be viral) To look for Strep. pneumoniae,
H. influenzae and Moraxella catarrhalis
o ECG : P pulmonale, RBBB, RV hypertrophy
o Echo
o Alpha 1 antitrypsin levels : In premature disease or non-smokers
 Management
o Smoking cessation
o Bronchodilators
 Beta 2 agonists:
 Antimuscarinics: Does not prevent decline of FEV1
 Theophylline : Little benefit

274
 
o PDE4 inhibitors : Anti inflammatory, Adjunct to bronchodilators, For FEV1 < 50% of
predicted and having chronic bronchitis
 Improves lung functions and exacerbations
o Corticosteroids
 More use in blood eosinophilia
 High doses increase pneumonia risk
 Given in frequent exacerbations and For FEV1 < 50% of predicted, Acute
exacerbations


o Antibiotics
 For acute exacerbations
 <antibiotic guideline>

275
 


o Mucolytic agents
 Carbocysteine: reduce exacerbation frequency
o Oxygen therapy
 Given for 19 hours,
 Indication
 PaO2 of <7.3 kPa (55 mmHg) when breathing air;
 PaO2 of <8 kPa with secondary polycythaemia, nocturnal
hypoxaemia, peripheral oedema or evidence of pulmonary
hypertension
 carboxyhemoglobin of <3% (i.e. patients who have stopped
smoking).
 Given by oxygen concentrator
o Pulmonary rehabilitation
o Vaccines
 Pneumococcal and influenza
 Covid
 Pertussis if not already vaccinated
 VZV if >50yrs
o Alpha 1 antitrypsin replacement
 IV route, reduce emphysema progression
o Treating heart failure

276
 o Venesection for secondary polycythemia (PCV >55%)
o Sedation
 For breathlessness, lorezapam or opiates
o Not recommended drugs – Antitussives and Vasodilators
o Surgery
 To reduce lung volumes, Bullectomy - No mortality benefit
 transplant
o Endobronchial valves

o
 Education
 Nutritional supplementation
 End of life palliative care
 COPD exacerbation
o Definition: Increase of symptoms or change of sputum colour/consistency that
required additional treatment than normal
o NIV is required if persistent respiratory acidosis with pH<7.35
 Prognosis of COPD
o Poor prognostic factors: increasing age, worsening airflow limitation
o BODE index gives a quantitative value

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TB
Check the “TB guidelines – a concise version for final MBBS” (pdf version)

Pneumothorax

Classification: -

1. spontaneous
a. Primary - age 15-34, in thin, tall, young, non-smoker
b. Secondary - age > 55, elderly patient, may be due to COPD, malignancy, necrotizing
pneumonia, asthma
2. Traumatic
3. Iatrogenic (pleural biopsy, mechanical ventilation trans bronchial biopsy ).

Presentation: - abrupt onset of pleuritic chest pain, with or without breathlessness, shoulder tip
pain.

Ix: -

1. standard erect PA chest x-ray

2. Lateral x -ray
3. Expiratory films
4. Supine and lateral decubitus x-ray
5. Uss
6. CT scan

Standard erect chest x-rays in inspiration are recommended for the initial diagnosis of
pneumothorax, rather than expiratory films

CT scanning is recommended for uncertain or complex cases

Mx: -

 A,B C approach
 Connect to a pulse oximeter and check 02 saturation
 Give high flow 02 via face mask.
 Assess PR,BP,tracheal deviation
 Gain IV access and connect multipara monitor
 If patient has tension pneumothorax (hypotension with increased JVP and tachycardia ),we
should do immediate needle aspiration, then put IC tube insertion .
 In any type of pneumothorax, if B/L or patient unstable, we should insert IC tube definitely.
 In stable patient after A B C, we should do erect CXR and confirm diagnosis.

278
In defining a management strategy, the size of a pneumothorax is less important than the degree of
clinical compromise.

The differentiation of a ‘large’ from a ‘small’ pneumothorax continues to be the presence of a visible
rim of >2 cm between the lung margin and the chest wall (at the level of the hilum) and is easily
measured with the PACS system. (Digital radiography)

Accurate pneumothorax size calculations are best achieved by CT scanning.

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Primary spontaneous pneumothorax

Size > 2cm or if patient is

symptomatic (SOB), we
should do needle aspirations
(16-18G cannula)

if size remain > 2cm and

Size <2cm, dyspnoea resolve
dyspnoea persist

No need to IC tube , IC tube(9-14Fr) should be

discharge and re-evaluate at inserted after insertion of IC
a later time conservative tube ,do CXR, and Give high
mx,reviews in 3-5 days. flow 02 via face mask.

High flow supplement 02 increase absorption of pneumothorax when it give via face mask and
supplement 02 accelerate the lung expansion.

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Secondary spontaneous pneumothorax

Secondary
spontaneous
pneumothorax

Size >2cm or if
patient 1-2 cm and no SOB < 1cm
symptomatic ( SOB)

admit the patient

First try needle
IC tube insertion and 02 and monitor
aspirations
for 24 hr

<1cm remain 1-2 cm

No need IC tube IC tube insertion

Admit the patient

and give 02 and
monitor for 24 hr.

In any situation after insertion of IC tube, we should do CXR always.

Also, if secondary spontaneous pneumothorax suspected, detect the primary cause for secondary
spontaneous pneumothorax and treat for that.

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Discharge and follow-up

 Patients should be advised to return to hospital if increasing breathlessness develops.

 All patients should be followed up by respiratory physicians until full resolution.
 Air travel should be avoided until full resolution.
 Diving should be permanently avoided

Tumors of the respiratory tract

Benign tumors

 Pulmonary hamartoma - The most common extremely slow growing tumor. Rarely cause
obstruction if arise from major bronchus. Seen in X ray as very well-rounded lesion in the
periphery of lung.
 Bronchial adenoma - Diverse group arising from mucus glands and ducts of windpipe.
 Cylindrical, chondroma and lipoma - Extremely rare in bronchus or trachea that causes
obstruction.
 Tracheal tumors - Include squamous papilloma, leiomyoma and hemangiomas.

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Solitary pulmonary nodules
Discrete pulmonary nodule <3cm in diameter and the DDx are;
 Primary bronchial Ca
 Pulmonary mets
 Inflammatory lesions (rounded pneumonia or abscess)
 Granuloma
 Benign tumors (hamartoma)
 Rheumatoid nodules
 Hydatid cyst
Majority are benign but need radiological follow up.

Malignant tumors

1. Bronchial Ca
Most common malignant tumor worldwide and most common cause of cancer related deaths.
Aetiology
 Environmental - Cigarette smoking, Radon exposure, asbestos, polycyclic aromatic
hydrocarbons, ionizing radiation; occupational exposure to As, Ni, Cr, petroleum products and
oils.
 Host factors - genetic factors; preexisting lung diseases as pul. fibrosis, HIV infection.
Lung Ca cell types
 Small Cell Lung Ca (20%)
 Arise from neuroendocrine cells.
 Arises centrally and metastasizes easily.
 Often secretes polypeptide hormones.
 Non-Small Cell Lung Ca
 Squamous Cell Ca (35%)
 Arises from epithelial cells, associated with production of keratin.
 Local spread common but metastasize relatively late.
 Causes obstructing lesions with post-obstructive infections.
 Adenocarcinoma (27-30%)
 Most common type in non-smokers.
 Arises from mucus-secreting glandular cells in peripheries of lungs.
 Metastases common.
 Large-Cell Ca (10-15%)
 Often poorly differentiated.
 Metastasize relatively early.
Clinical features
 Local effects
 Cough, breathlessness, haemoptysis, chest pain, wheeze,
 Recurrent infections, stridor and SVC obstruction
 Nerve involvement
 Hoarse voice (left recurrent laryngeal nerve compression)
 Pancoast tumors (C8/T1 invasion) - hand small muscle wasting and weakness, pain
radiating down the arm.
 Horner's syndrome (sympathetic chain compression) - miosis, ptosis and
anhidrosis
 Direct invasion of phrenic nerve - ipsilateral hemidiaphragm paralysis; involve
oesophagus (progressive dysphagia) and pericardium (pericardia effusions and
malignant dysrhythmias)

283
  Metastatic spread
 Commonly mediastinal, cervical and axillary or intra-abdominal nodes
 Liver, adrenal glands, pleura, bones, brain and skin

 Non metastatic extrapulmonary manifestations

 Endocrine (usually SCLC)
 Ectopic adrenocorticotrophin syndrome
 SIADH
 Hypercalcaemia (usually seen in squamous cell Ca)
 Rare; hypoglycemia, thyrotoxicosis, gynecomastia
 Neurologic (typically associated with SCLC)
 Encephalopathies - limbic encephalitis, encephalomyelitis, subacute cerebellar
degeneration (cerebellar ataxia)
 Myelopathies - motor neuron disease
 Neuropathies - peripheral sensorimotor neuropathy, autonomic neuropathy
 Muscular disorders - polymyopathy, Lambert-Eaton myasthenic syndrome
 Skeletal
 Clubbing (30%)
 Hypertrophic osteopathy (3%)
 Hematological and vascular (rare)
 Normocytic anemia and thrombocytosis relatively common
 Thrombophlebitis migrans, non-bacterial thrombotic endocarditis, DIC, TTP
 Cutaneous (rare)
 Dermatomyositis, acanthosis nigricans, herpes zoster

Investigations
 Diagnosis
 Chest X-ray, CT/ PET-CT (TNM staging)
 MRI not useful in diagnosing primary lung tumors except Pancoast tumors with nerve
invasions
 Bone scan
 Histology and cytology
 Fiberoptic bronchoscopy
 Endobronchial USS
 CT/ USS guided biopsy of lung lesions, lymph nodes, liver mets and skin lesions
 USS guided pleural effusions
 Medical/ video assisted thoracoscopy
 Mediastinoscopy
 Other Ix
 FBC for anemia
 Biochemistry for liver involvement, hypercalcaemia, hyponatremia
 Fitness for surgery; full lung functions, cardiopulmonary exercise testing, stress echo

Management
Most patients have advanced lung Ca at the stage of presentation, hence radical treatment is not an
option.
NSCLC have only 25-30% 1 year survival after diagnosis and only 6-8% 5-year survival.
SCLC staged as limited or extensive.
Surgery
 For early stage (stage I, II and selected IIIA) NSCLC
 Those with stage III may be possible to undergo surgery after chemoradiation

284
  After surgical resection if there is nodal involvement, they require adjuvant chemotherapy.
Radiation therapy
 For those with adequate lung function and early NSCLC
 Good alternative for surgery and treatment of choice for those who can't undergo surgery due
to co-morbidities.
 Radiation pneumonitis (within 3 months of radiation therapy) in 10-15% of cases.
 Radiation fibrosis not confining to the area of treatment happens in some degree in all cases.
 Palliative radiation therapy;
 Those with bone and chest pain due to mets or direct invasion, hemoptysis, occluded
bronchi and SVC obstruction respond favorably to radiation in short term.
Chemotherapy
 Adjuvant chemotherapy with radiotherapy
Targeted therapy
 Targeted therapy for adenocarcinoma
 Used if chemotherapy offers unacceptable toxicity or as second line chemotherapy.
Palliative care
 Laser therapy, cryotherapy and tracheobronchial stents are used in palliation of inoperable
lung Ca where there is tracheobronchial narrowing causing disabling breathlessness,
intractable cough and complications like infection, hemoptysis and respiratory failure.

2. Bronchial carcinoid tumors

 Rare, slow-growing, low-grade malignant neoplasms and staging same as NSCLC.
 Arise from neuroendocrine tumors.
 Surgery treatment of choice but need long term surveillance.

3. Mesothelioma
 Malignant tumor arising from parietal or visceral mesothelial lining of the lung.
 Almost always related to asbestos exposure and develops from pre-existing pleural plaque
disease.
 Most present with a pleural effusion, typically with persisting chest wall pain.
 May need image guided pleural biopsy to diagnose.
 Poor outcome

4. Secondary tumors
 Typical sites for primary tumors are kidney, prostate, breast, bone, GI tract, cervix and ovary.
 Stomach, pancreatic and breast Ca can involve mediastinal glands and spread via lymph to
involve both lungs; on CXR B\L lymphadenopathy seen together with streaky basal shadowing
fanning out.
 Single pulmonary mets can be removed surgically; but need extensive Ix prior.

285
Bronchiectasis

Acute infective Out-patient In immediate Caution:

exacerbation of penicillin or ciprofloxacin,
bronchiectasis co-amoxiclav 625mg cephalosporin levofloxacin and
po 8 hourly or hypersensitivity moxifloxacin
cefuroxime 500mg po (quinolones) can
12 hourly clarithromycin or mask / promote
doxycycline resistance of
In-patient Mycobacterium
co-amoxiclav 1.2g IV 8 Duration: 7-10 tuberculosis and
hourly days atypical
or mycobacterial
Cefotaxime 1-2g IV 8 infections
hourly or ceftriaxone
1-2g IV daily

Duration : 7-10 days

Bronchiectasis with Out-patients piperacillin–
Previous ciprofloxacin 500- tazobactam or
microbiologically 750mgpo12 hourly meropenem or
confirmed or suspected imipenem
Pseudomonas infection In-patients
ceftazidime 1-2g IV
8hourly Duration: 14
days

286
Interstitial Lung Disease (Diffuse parenchymal lung disease)

 A heterogeneous group of conditions

Clinical Features Investigations Management

Sarcoidosis Combination of bilateral - Chest Xray (beading
hilar lymphadenopathy, appearance)
erythema nodosum, - HRCT
arthralgia, and fever - FBC (N/N anemia)
(Löfgren’s syndrome) - ESR (raised)
- Renal biopsy
- 24-hour urine calcium
excretion
(Hypercalcemia)
- ECG and 2D Echo
- Bronchoalveolar lavage
- Lung function tests
Spontaneous resolution
is seen typically within 6
months
Systemic treatment
- Corticosteroids
(Prednisolone 0.5mg/kg
for 4-6 weeks gradually
tapering over 12 months)
- Immunosuppressants
(Methotrexate,
azathioprine, HCQ)

Lung transplant
(If severe/ stage IV/
respiratory failure)
Hypersensitivity Weight loss, malaise, - Chest Xray (diffuse small Need to avoid exposure
Pneumonitis dyspnoea, cough, nodules, increased to inciting antigen (if
inspiratory squeaks, reticular shadows) known)
bilateral fine - HRCT
crepitations. - Lung function tests Prednisolone
- Precipitating antibodies
in serum
- Bronchoalveolar lavage
- Lung biopsy
Idiopathic pulmonary Insidious onset - Respiratory function Immunosuppression is
fibrosis progressive dyspnoea tests (Restrictive pattern) generally AVOIDED!
with cough, sputum - ANA levels
production, bi-basal end- - Rheumatoid factor Pirfenidone
inspiratory crepitations, - Chest Xray Nintedanib
finger clubbing - HRCT
- Bronchoalveolar lavage
- May need histological
confirmation

287
288
Venous Thrombo-Embolism (VTE)

Pulmonary Embolism (PE) and Deep vein thrombosis (DVT)

 In up to 50% of people no cause can be established
 Need to be aware because it is,
- Common
- Life-threatening
- Preventable
- Difficult to diagnose
- Treatment can be hazardous
- A significant cause of morbidity

Thrombosis is the pathological process by which a localized solid mass of blood constituents (a
blood clot or thrombus) forms within a blood vessel and fragments (emboli) may break off and
occlude vessels downstream.

Virchow’s triad:

1. Changes in blood flow (stasis or

turbulence)
2. Vessel wall dysfunction
3. Changes in blood components,
leading to hypercoagulability.

Clinical features

 DVT: Pain and swelling in one leg. Leg may be warm, red and tenderness along the course of
deep veins
 PE:
o 65%: Pleuritic chest pain and breathlessness +/- Haemoptysis. Tachypnoea and
tachycardia typically present. Auscultation- Crackles and pleural rub
o 25%: isolated breathlessness
o 10%: More severe features (Syncope, systolic hypertension, myocardial
ischemia)

289
Initial investigations

1) ECG: S1Q3T3 with sinus tachycardia commonly

2) Chest X-ray: atelectasis, parenchymal abnormalities,
cardiomegaly, pleural effusion
3) ABG analysis: hypoxia and hypocapnia
4) Biomarkers:
a. Plasma BNP level/ its precursor amino terminal
pro-BNP elevated
b. Troponin elevated

Diagnosis

1) Clinical presentation
2) Assessment of clinical (pre-test) probability - Likely vs
Unlikely
Using score systems,
a. Two-level Wells score for DVT
b. Two-level wells score for PE
3) D-dimer measurement
4) Imaging
a. DVT: Ultrasonography +/- Doppler
b. PE:
i. CT Pulmonary Angiography
ii. Ventilation-perfusion (V/Q) isotope
lung scanning
 Diagnostic testing for VTE should be done urgently and
completed within 24 hours of initial presentation.
 Anticoagulants should be given if it is anticipated that
it will take,
o More than 4 hours to investigate a suspected
DVT
o More than 1 hour to investigate a suspected
PE

290
291
Management

Standard treatment: Anticoagulant therapy

Mainly 3 phases

1) Acute phase, lasting 5 -10 days

2) Maintenance phase, lasting till 3 months
3) Long-term phase, beyond 3 months

1) Acute phase
a. Haemodynamic and respiratory support
i. Oxygen therapy and ventilation
ii. Pharmacological treatment of acute right ventricular failure
iii. Mechanical circulatory support and oxygenation
iv. Advanced life support in cardiac arrest

b. Initial anticoagulation
i. Parenteral anticoagulation
ii. Non-vitamin k antagonist oral anticoagulants
iii. Vitamin K antagonists
c. Reperfusion treatment
i. Systemic thrombolysis
ii. Percutaneous catheter-directed treatment
iii. Surgical embolectomy
d. Multidisciplinary Pulmonary embolism team
e. Vena cava filters
2) Maintenance phase
- Anticoagulation needs to continue for a minimum of 3 months in ALL PATIENTS with
proximal DVT or PE (Earlier discontinuation associated with high risk of recurrence)
3) Long-term phase
- After 3 months, whether to stop anticoagulation or not is decided based on,
o An individual patient basis
o Risk of recurrence
o Risk of bleeding
o Patients’ expectations

Complications of VTE

1) Mortality
2) Associated cancer
a. Trousseau’s syndrome
3) Post-thrombotic syndrome
4) Pulmonary hypertension

Investigations of newly diagnosed VTE

1) General investigations
a. FBC
b. Renal function test

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 c. Liver function test
d. Clotting screen
e. Chest X-ray
f. Urinalysis

2) Thrombophilia testing
a. Heritable thrombophilias
b. Acquired thrombophilia
i. Antiphospholipid syndrome

Prevention

 Almost ½ of all episodes of VTE are provoked by surgery and/or admission to hospital
 All adults admitted to hospital need formal assessment of their risks of VTE and Bleeding

Prophylaxis

a) Mechanical
a. Early mobilization
b. Elevation of the legs
c. Anti-embolic stockings
d. Intermittent compression devices
b) Pharmacological
a. Anticoagulants
i. Parenteral
1. Unfractionated Heparin
2. LMWH
3. Fondaparinux

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 ii. Oral
1. Vitamin K antagonists
a. Warfarin

2. Direct oral anticoagulants

a. Apixaban
b. Rivaroxaban
c. Edoxaban
d. Dabigatran

Sources:
1. Kumar and Clerk 10th Edition
2. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism,
developed in collaboration with the European Respiratory Society (ERS

Pulmonary hypertension

PH mean Pulmonary Arterial Pressure (mPAP) >25mmHg at rest, as measured on right heart
catheterization.
Changes seen in PH;
 Hypertrophy, proliferation and fibrotic changes in distal pulmonary arteries.
 Pulmonary venous changes
 Vascular bed destroyed in emphysematous or fibrotic areas
 Organized thrombi in elastic pulmonary arteries
 Patients with progressive PH develop right ventricular hypertrophy, dealation, heart failure
and death.

Etiology
 Idiopathic (IPAH)
 Familial/ heritable
 Drugs and toxins - fenfluramine, dexfenfluramine, toxic rapeseed oil
 Autoimmune rheumatic disease
 Congenital heart disease
 Portal hypertension
 HIV associated disease

Clinical features
 Symptoms of dyspnea, fatigue, weakness, angina, syncope and abdominal distention

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  Signs include left parasternal heaves, loud P2, soft pansystolic murmur with TR or early
diastolic murmur with PR, features of right heart failure
 Clinical signs of associated diseases - systemic sclerosis or CLCD

Investigations
 FBC, renal and liver biochemistry, thyroid function tests, serology for autoimmune diseases,
HIV and hepatitis.
 CXR - enlargement of pulmonary arteries and major branches, with marked pruning of
peripheral arteries. Lung fields usually lucent and there may be right atrial and ventricular
enlargement
 ECG - right ventricular hypertrophy and P pulmonale
 Echo - can use to determine PAP
 USS abdomen - exclude CLCD and portal htn
 Right heart catheterization - to confirm diagnosis

Management
 Physical activity - should remain active but avoid exertion that precipitate dyspnea, chest pain
or pre-syncope
 Pregnancy - should avoid and use contraception like barrier methods, POP, LNG- IUS
 Travel - supplementary Oxygen (2L/min) when air travel
 Vaccination - influenza and pneumococcal
 Anesthesia - epidural > general
 Oral anticoagulants
 Diuretics - in RHF and fluid overload
 Digoxin - in tachyarrhythmias
 CCBs
 Prostanoids - symptomatic relief and improve exercise capacity (epoprostenol - improve
survival in IPAH)
 Endothelin receptor antagonists - improve symptoms, exercise capacity and hemodynamics in
IPAH
 Phosphodiesterase type 5 inhibitors - symptomatic relief and improve exercise capacity in
IPAH
 Balloon atrial septostomy - palliative therapy in sever PH
 Lung transplantation - 5 year survival only 40-50%

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Respiratory system Drugs

296
297
298
10. Toxicology
Management of acute poisoning
 Acute poisoning is a medical emergency. Follow ABC approach
 Clear the airway by removing secretions
 Remove dentures
 Put the patient into left lateral position
 If respiration is impaired, give oxygen and consider assisted ventilation or intubation
 Gain IV access to administer antidotes and IV fluids (*antidote treatment has priority over GI
decontamination)
 Supportive therapy (maintain fluid balance chart, monitor SE) and anticipate cardiac, hepatic,
renal and respiratory failure
 GI decontamination
 Only considered in stable patients within 1-2h of ingestion of poison (*but patients
following ingestion of controlled release preparations, carbamazepine, kaneru may
benefit from decontamination even after a long delay)
 Methods
1. Activated charcoal (best evidence of benefit)
 1g/kg (all ages)
 Adsorbs poisons into activated charcoal and reduces absorption of
poisons from GIT
 Activated charcoal is suspended in 200 ml of water and administered
orally or via NG tube (*multiple dose activated charcoal therapy used
for controlled release drugs, kaneru seeds)
 Acids, alkali, iron are not effectively adsorbed by activated charcoal
2. Gastric aspiration and lavage
 Should not exceed 200-400 ml for adults each cycle and it is
rare to require more than 3 cycles
 Lavage tube should have a rounded end, should be firm and
flexible (18 G NG or Ryle’s tube)
 First sample aspirated should be labeled and preserved for
toxicological analysis
 Equivalent or inferior to activated charcoal
 Corrosive (acids or alkalis) ingestion is a contraindication
3. Emesis
 Major indication for emesis is as first aid at home
 Continuous ECG and SPO2 monitoring

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  Elimination of absorbed poisons
1) Alkaline and acid diuresis
2) Peritoneal dialysis
3) Hemodialysis
4) Hemoperfusion
 Discharge after psychiatry referral

Pesticides Drugs Plant poisons

1. Carbamate 1. Anticholinergics (Atropine,TCA, 1. Ricinus communis
2. Glyphosate hyoscine,Datura stramonium- (Endaru)
3. Organophosphates Attana) 2. Strychnos nux vomica
4. Paraquat 2. Benzodiazepines (Goda kaduru)
5. Propanil 3. Asprin 3. Nerium oleander
4. Hypoglycemic drugs (Kaneru)
5. Opiates 4. Gloriosa superba
6. PCM (Niyagala)

Pesticide/Drug/Plant Clinical features Management Important

poison facts
Carbamate Toxic effects are similar to *Mainstay is atropine
(*anticholinesterase) organophosphates *Pralidoxime not normally required
Glyphosate *epigastric pain, dysphagia,N,V *Cimetidine or ranitidine
*Irritation due to skin contact *Diazepam for convulsions
*oral/nasal discomfort due to *Correction of metabolic acidosis
inhalation with IV NaHCO3
Organophosphate 1.Muscarinic effects *Presence of *Also, pralidoxime
(*anticholinesterase) (N,V,diarrhea,sweating,small bronchospasms/crepitations, pin can be used
pin point point pupils, excessive sweating
pupils,dyspnea,cyanosis,brad suggest that patient needs atropine
ycardia) (if none present, KUO)
2.Nicotinic effects (muscle *If clinical presentation is not clear
twitching, fasciculations) but OP poisoning is a possibility; give
*After apparent recovery, 0.6-1 mg atropine (*0.6 mg in an
sudden respiratory failure atropine vial)
may develop 24-96h after *For unconscious patients, atropine
poisoning with some 1.8-3 mg IV rapidly
organophosphates known as *In 3-5 min, if no improvement in
intermediate syndrome cholinergic effects, double the dose
(delayed onset of muscle and continue to double each time if
weakness and paralysis) no response
3.CNS effects * Once atropinised; patient will
(headache,ataxia,convulsions have,
) 1) Clear lungs
2) Adequate heart rate(80-
Cholinergic syndrome in 100bpm)

300
 severely poisoned patients 3) SBP>80 mmHg with good
 Poor air entry due to UOP
bronchospasms 4) Dry axilla
 Excessive sweating 5) Pupils no longer pin point
 Bradycardia *Start atropine infusion assessing the
 Hypotension cholinergic features
 miosis *Features of excess atropine
1) Confusion
2) Urine retention
3) Hyperthermia
4) Bowel ileus
5) Tachycardia
If these features present, stop
atropine infusion
Paraquat *early features (burning *Adsorbent- Fuller’s Earth *Inactivated by
sensation in mouth and contact with soil
throat,N,V,abdominal pain)
*late features (liver and renal
toxicity)
Propanil *N&V,abd.pain *Gastric lavage,IP/OP *Meth
*Cyanosis,acidosis chart,hydration,bed rest. hemoglobinaemia
*Headache,dizziness,convulsio 100% O2 +/- assisted ventilation
ns *Measure meth haemoglobin if
*Bradycardia possible
*Respi depression *Give 1% methylene blue.
*Heinz body hemolytic anaemia *If not responding-exchange
transfusion
*Oxymeter readings unreliable due
to colour change in blood
Anticholinergics *Tachycardia,HTN,Orthostatic *ABC +/- ventilation & O2
hypotension *Ice bags/tepid sponging/fanning-
*Dilated pupils fever
*Urine retention *Catheterize
*Hyperthermia,agitation>myog *Diazepam IV
lobinuria
Benzodiazepine *Drowsiness,ataxia,dysarthria,r *Flumazenil *Rarely cause death
espi. Depression *But most pts need only supportive but if taken in
care combination with other
sedatives can be fatal
Aspirin *N&V,burning epistemic & *ABC *Toxic dose-300-500
throat pain,hemetamesis *IP/OP chart,hydration mg/Kg
Tinnitus,deafness,hyperthermi *Antacids,H2 R blockers >100mg/dl-lethal
a,tremor,delirium,convulsions, *Correct electrolytes & glucose
coma Diazepam IV
*Hyperventilation *Sponging/ice
*Metabolic acidosis/respi *Enhance aspirin elimination-urine
alkalosis alkalization/dialysis
*Electrolyte
imbalances,hypoglycemia

TCA *Anti cholinergic-dry *ABC *Anticholinergic

301
 mouth,blurred vision,dilated *Activated charcoal/gastric lavage
pupils,urine *Treatment convulsions,acidosis
retention,constipation *Continuous cardiac monitoring
*CNS toxicity-convulsions, *Plasma alkalinization using
delirium,coma,hallucinations,o NaHCO3/hyperventilation
phthalmoplegia,myoclonic
twitches
*Cardiac toxicity-
tachycardia,HTN/hypotension,
SVT & arrhythmias
*Respi depression
*Hypothermia/pyrexia
Hypoglycemic drugs *Hypoglycemia- *ABC
confusion,fainting,ataxia,coma *Oral glucose/sweets/50ml
*Absent deep tendon 50%dextrose blouse>5%dextrose
reflexes,extensor plantar,focal infusion
neuro deficits *Correct metabolic acidosis
*Hypotension,tachycardia *Diazepam IV-convulsions
Lactic acidosis *Octreotide
Opiates *Pin point pupils,impaired *ABC *Modes of poisoning-
consciousness,respi depression *IP/OP chart ingestion,injection,inhal
*Bradycardia,hypotension,slow *Gastric lavage/activated charcoal ation,body packing
breathing *Naloxone 0.8-2mg IV repeat at
Noncardiogenic Pul. Oedema intervals of 3 mins to a max of 10mg
*Withdrawl-
diarrhoea,sweating,dilated
pupils.

PCM *Asymptomatic *Risk assessment by Hx,clinical *Single overdose->20

*Protracted vomiting if high assessment & plasma levels(not tablets(>10g) or
dose ingestion freely available in SL) >200mg/kg-potentially
Organ injury begins 10h after *If plasma levels available send bld fatal
*Elevated transaminases by 24 within 4-16h of ingestion. >100mg/kg/day-
h & peak at 3-5 days *On admission do-plasma hepatotoxic
PT/INR Prolongation levels,FBC,PT/INR,RFT,SE,urine Fatal outcome indicators
Phase 1- analysis,bld glucose Acidosis(pH <7.3)
Asymptomatic/features of GI *Repeat these Ix daily Grade 3/4
irritation *Reduce absorption-activated encephalopathy
Arrhythmias charcoal/gastric lavage PT>100s/INR>6.5
Biochemical evidence of liver *IP/OP chart Scr>300
failure not detectable *Vit K/FFP *Normal PCM dose for
Phase 2- *Hemodialysis if RF + children-10-15mg/kg
Hepatotoxicity(elevated Acute liver failure mx NAC can cause mild
transaminases,PT/INR,bilirubin *Antidotes-NAC,methionine anaphylaxis.but
RHQ pain/tenderness Give NAC if, complete NAC once
Phase3- >20 tablets ingestion/ no. Of tablets reaction settles
Bleeding unknown *MSI(multiple
manifestations,hepatic Give methionine if, supratheraputic
encephalopathy,high bilirubin Within 8h ingestion)/staggered
Renal tubular necrosis-oliguric NAC vs Methionine overdose
RF,acidosis,Electrolyte *NAC, -more than one

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 imbalances -high cost(4 times methionine) ingestion of PCM over a
Thrombocytopenia,Hypoglyce Given for pts after 8h of ingestion,pts period of 8h that result
mia,DIC with high transaminases,pts at risk of in cumulative dose
Pancreatitis,myocarditis hepatic encephalopathy >100mg/kg/day
Phase 4- Given even after 24h if symptomatic Multiple minor
Complete resolution in 7-10 *Methionine overdoses over few days
days or death Cheap may cause severe liver
Severe liver necrosis may show Within 8h only damage
residual scarring Given for asymptomatic also if taken
toxic doses
Both drugs have same efficacy

Ricinus communis *Latent period of several hrs *Activated charcoal/lavage *These seeds are
(Beheth enderu) *N & V,abdominal pain *IP/OP chart,correct electrolytes poisonous only if they
Diarrhoea>dehydration,electro *Treat shock are chewed or smashed
lyte imbalances,cramps,shock *Dialysis if needed, NaHCO3 to *Toxin is Ricin which is
Hypoglycemia,retinal alkalinize urine the most powerful plant
h'ges,hematuria,convulsions,h poison
epatic necrosis,acute RF Castor oil is not
poisonous but residue is
highly poisonous

Strychnous nux vomica *Muscle *ABC

(Goda kaduru) twitching,anxiety,dilated *Diazepam & other anticonvulsants if
pupils,hyperthermia not settled
Symmetrical painful *Lavage/activated charcoal
convulsions(with risus *NaHCO3
sardonicus & opisthotonus)
Rhabdomyolysis,myoglobinuria
,RF

Nerium oleander *N&V,hyperkalemia *Observe in hospital for 24h even *if Presence of cardio toxins
(Kaneru) Bradycardia,hypotension,ventri asymptomatic
cular arrhythmias Lavage/activated charcoal/whole
Xanthopsia,anxiety,convulsions bowel irrigation
,coma *IP/OP chart,SE
*Diazepam for convulsions
*Atrophine bolus or infusion if
severe brady(<40) or 2nd degree AV
block
Gloriosa superba *Severe gastroenteritis-abd *ABC *Toxin - colchicine
pain,N&V,bloody *lavage/activated Colchicine affects
diarrhoea>electrolyte *charcoal/vomiting induction normal cell division
imbalance,dehydration,hypote *IP/OP,IV fluids *All parts of niyagala are

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(Niyagala) nsion,shock *Correct electrolytes,IV NaHCO3 poisonous.
*Granulocytopenia,Thrombocy *After correcting shock &
topenia,clotting defects dehydration-forced diuretics for 1st
*Arrhythmias,polyneuropathy, 24h followed by adequate diuretics
convulsions,coma up to 3rd day
*Hepatic& renal failure
*Alopecia
*Respi depression

Snake bites
 Common snakes in Sri Lanka
1) Cobra-Naja naja naja
2) Common krait-Bungarus caeruleus
3) Ceylon krait-Bungarus ceylonicus
4) Russell’s viper-Daboia russelli russelli
5) Saw scaled viper-Echis carinatus
6) Hump nosed viper- Hypnale nepa
7) Sea snake

Snake Clinical features (signs of envenomation) Characteristic appearance

Russell’s viper *local swelling *3 longitudinal rows of chocolate

*neurotoxicity(ptosis) brown oval patches along the body
*coagulopathy
*rhabdomyolysis
*acute renal failure

Cobra *local swelling and tissue necrosis

*neurotoxicity(ptosis, respiratory
paralysis, limb paralysis)

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Krait *neurotoxicity(ptosis, respiratory *large, polygonal vertebral scales
paralysis)

Hump nosed viper *local swelling and haemorrhagic blisters *upturned snout with loreal pit(pit
*coagulopathy between eye and nostril)
*Acute renal failure

*local swelling *white dagger mark on head

*coagulopathy *saw toothed body scales
*acute renal failure

Saw scaled viper

Sea snake *rhabdomyolysis *flattened, paddle like tail

*bites are painless with no local
inflammation
*neurotoxicity

 Management after a snake bite

1) First aid
 Reassure the anxious patient and wash the bite site
 Immobilize the bitten limb with a splint
 Arterial tourniquets not recommended
 Transport the patient to a hospital quickly

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2) Rapid clinical assessment and resuscitation following admission
3) Assess clinical signs of envenomation and investigations (20 WBCT-20 min whole
blood clotting test,FBC,blood picture,CPK,LFTs,Scr,BU,K,UFR)
4) Identification of the snake
5) Tetanus prophylaxis before the discharge
6) Antivenom administration
*If there are features of systemic envenomation (neurotoxicity, rhabdomyolysis
etc.), give antivenom
*If there are features of local envenomation only or no features of envenomation
but there is a definite history of bite by a venomous snake or presence of fang mark,
observe for at least 24h and watch for the signs of systemic envenomation. If no
signs of systemic envenomation develop, discharge the patient. If the signs of
systemic envenomation develop, treat with antivenom
*Avoid NSAIDs, IM injections whenever possible
*Antivenom therapy is given only for bites of Russell’s viper, Cobra, Krait, Saw scaled
viper. It is not given for hump nosed viper, green pit viper, sea snakes
*Antivenom therapy available in Sri Lanka is Indian polyspecific AVS- dose-100 ml(10
ampoules) in 200 ml of normal saline infused IV over 1h
*In viper bites, repeat in 6h if coagulopathy persists. In cobra/ krait bites, usually 1
dose of AVS is sufficient if not deteriorating
*Antivenom should never be given IM if it can be given IV
*After antivenom administration, systemic bleeding may stop in 40 min, blood
coagulability restored in 6h, neurotoxicity begins to improve in 30 min,
rhabdomyolysis resolves in 2h.
*Antivenom may cause anaphylaxis
7) Management of special problems (ARF, respiratory failure, bacterial infections,
compartment syndrome)
8) Treatment of bitten part
9) Rehabilitation (physiotherapy etc.)
10) Prevention of snake bites (education/ wear boots or use light when walking at night/
never handle snakes/ avoid sleeping on ground)

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11. Infections
Brucellosis
 Bacilli travels through lymphatics and then localizes in the reticuloendothelial system.
 Portals of entry- mouth, respiratory tract, genital tract, abraded skin, rarely person to person
 By ingesting raw milk from infected cattle, occupational exposure
 Clinical features- malaise, headache, weakness, generalized myalgia, night sweats,
lymphadenopathy, hepatosplenomegaly, sacroiliitis, arthritis, meningoencephalitis
 Fever pattern- undulant/ continuous, intermittent
 If untreated goes into a chronic disease.
 Dx- blood culture, serology, Brucella agglutination test showing 4-fold rise is highly suggestive.
 Tx-Doxycycline + rifampicin+ gentamycin
 Preventive strategies are important. No vaccine is available.

Leprosy (Hansen’s disease)

 By Mycobacterium leprae which is a type of acid fast bacilli.
 Poverty, overcrowding, male sex are risk factors
 2 polar types
1. Tuberculoid leprosy- A localized disease in patients with good cell mediated immunity
(CMI).
2. Lepromatous leprosy- A generalized disease that occurs in patients with impaired CMI.
 WHO classification
1. Paucibacillary leprosy- <6 skin lesion without any bacilli
2. Multibacillary- >6 skin lesions that may have bacilli
Many patients fall in between these 2 extremes and some may move along the spectrum.
 Incubation period- few months as long as 20 years
 Insidious in onset
 Clinical features vary according to 5 clinical groups

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 Essentially a clinical Dx with
o Hypopigmented/ reddish patches with loss of sensation
o Thickening of peripheral nerves
o AFB seen on skin-slit smear ort biopsy
 Mx
o Multidrug treatment is essential to prevent the emergence drug resistance
o Recommended treatment regimens- WHO guidelines

 Immunological/lepra reactions may occur while on treatment especially in borderline &

lepromatous disease.

Enteric fever
 Typhoid is the typical form of enteric fever; caused by Salmonella typhi.
 Paratyphoid is a similar but a less severe form of illness; caused by Salmonella paratyphi.
 Humans are the only natural host.
 Incubation period is 10-14 days
 Clinical features- characterized by fever, headache, abdominal discomfort
o Onset- intermittent fever, headache, abdominal pain, abdominal tenderness,
hepatosplenomegaly, lymphadenopathy, scanty maculopapular rash (rose spots)

308
 o If left untreated during the 3rd week- meningitis, lobar pneumonia, osteomyelitis,
intestinal perforation & intestinal haemorrhage.
o After clinical recovery some may continue to excrete S.typhi for several months; known
as convalescent carriers.
o Some may continue to carry the organism for >1 year- known as chronic carriers.
o In paratyphoid fever complications are uncommon and the disease is less severe.
 Dx- Definitive Dx is by culture
o Blood culture in first 2 weeks
o Culture of feces, urine
o Bone marrow culture is more sensitive than blood culture but is rarely used, except in
patients who’ve already received antibiotics.
o FBC- leucopenia
o Widal test is not accurate.
 Mx
o Resistance is emerging
o Drug of choice- Ciprofloxacin 500mg bd; if resistant azithromycin/ ceftriaxone
o Chloramphenicol, co-trimoxazole & amoxicillin are also used.
o Body temperature may remain elevated even after treatment for several days.
o Carriers need prolonged antibiotics.
o Cholecystectomy is not useful.
 Vaccines (oral live attenuated/ injectable inactivated) give partial protection.

Typhus
 Collective name given for diseases caused Rickettsia species.

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 Epidemic typhus- Incubation period is 1-3 weeks; abrupt onset of fever with malaise, myalgia,
headache, conjunctivitis, orbital pain, measles like eruption on 5th day; at the endo of 1st week
meningoencephalitis occurs and progress to coma
 Scrub typhus- Eschar is seen at the site of bite; variable clinical course; more severe cases
resemble epidemic typhus; unlike other types of typhus the organism is passed on to
subsequent generations of mites, which act as both reservoir & vector.
 Endemic typhus- resembles epidemic typhus but less severe
 Spotted fever group- typical feature is the widespread petechial rash; incubation period is 4-10
days, eschar, regional lymphadenopathy, abrupt onset of fever, myalgia, headache,
maculopapular rash
 Dx- Mainly clinical Dx which can be confirmed by PCR or serology.
 Mx- Doxycycline for 5-7 days; ciprofloxacin is also effective
o If resistant rifampicin is used.

Melioidosis
 Caused by Burkholderia psedomallei which is a gram negative facultative intracellular organism.
 Saprophytes- found in soil & surface water
 Occurs through inhalation or direct inoculation.
 Majority are immunocompromised; commonly diabetes
 Causes wide spectrum of disease and the majority are subclinical.
 May be acute or chronic; localized or disseminated
 Multiple metastatic abscesses may occur.
 Dx- Isolating the organism form the blood or appropriate tissue.
 Has extensive intrinsic antibiotic resistance
 Tx
o Ceftazidime IV for 2-4 weeks followed by co-amoxiclav or co-trimoxazole for several months.

Candidiasis
 Most common fungal infection
 Caused predominantly by candida albicans
 Small asexual yeast
 Are commensals
 Most candidiasis is superficial
 Vaginal & oral thrush -most common forms
 Seen in very young, elderly, pts on antibiotics, immunosuppressed
 Candidal oesophagitis- painful dysphagia
 Cutaneous oesophagitis-seen in intertriginous areas
 A cause for paronychia
 Invasive candidiasis associated with intravascular devices
 Rx- depends on site and severity
• Superficial lesions - topical nystatin, amphotericin B
• Invasive - IV amphotericin B
 High risk of Ab resistance

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Malaria

Caused by p. falciparum, p. vivax, p. ovale, p. malariae, p. knowlesi.

Temperature-dependent life cycle
Seen in tropics and subtropics
Transmission-
Anopheles mosquito, contaminated blood transfusions, Iv drug use

Parasitology
• Gametocytes-sexual form. Taken in by a blood meal to the mosquito
• Sporozoites - form inoculated into the new human host
• Merozoites- form multiplying inside hepatocytes and take up by red cells
• Hypnozoite - p vivax,p ovale remain dormant in liver. Causes relapsing infections
• Inside red cells -cycle of merozoite, schizoid, trophozoite, new merozoites

Each red cell cycle is called erythrocytes progeny.

It is 48hrs - falciparum, vivax, ovale.... 72hrs - malariae

P vivax,p. Ovale - attack reticulocytes and young rbc

P malariae - older cells
P falciparum - any stage

Pathogenesis
Anemia, cytokine release
Causes of anemia in malaria
• Hemolysis of infected red cells
• Hemolysis of non-infected cells (Blackwater fever)
• Dyserythropoiesis
• Splenomegaly and sequestration
• Folate depletion

Some genetic traits confer immunity - Duffy antigen against p vivax

Seen in West Africa

Some Protective effect against malaria - sickle cell and iron deficiency anemia

Incubation period 10-21 days

C/f
Fever, rigors, drenching sweats
General malaise, headache, vomiting, diarrhoea
Tender hepatomegaly
 P malariae -in children associated with glomerulonephritis and nephritis syndrome
 P falciparum - serious complications - cerebral malaria, Blackwater fever
 Cerebral malaria - diminished consciousness, confusion, convulsions,coma and death
 Blackwater fever - widespread intravascular hemolysis

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 Tropical splenomegaly syndrome - exaggerated immune response to repeated malarial
infections -anemia, massive splenomegaly, elevated IgM levels
 Diagnosis
Giemsa stained thick and thin blood film
At least 3 films needed
Rapid antigen tests available

 Rx-
All cases of malaria - can use artemisinin combination therapy
P vivax and p ovale - primaquine 2-3 weeks -to eradicate hepatic hypnozoite relapses
Primaquine precipitate hemolysis in g6pd deficiency
Artemesinin derivatives- not used as monotherapy due to resistance

 Severe falciparum malaria

Iv artesunate more effective than iv quinine
Complications -hypoglycemia, severe anemia, metabolic acidosis

Prevention
Mosquito eradication
Chemoprophylaxis

Leishmaniasis

 Caused by leishmania genus

 Transmission- female phlebotomine sandfly
 In some areas, zoonotic.
 3types
1. Visceral leishmaniasis- L.donovani
2. Cutaneous leishmaniasis - L.tropica
3. Mucocutaneous leishmaniasis
 Vertebrate host - oval amastigote
 Sandfly- flagella promastigote
 C/F
Cutaneous leishmaniasis- painless nodules develop onto ulcers with erythematous borders.
Visceral leishmaniasis- fever, hepatosplenomegaly, lymphadenopathy
Associated with HIV coinfection

 Dx
Cutaneous leishmaniasis-
• giemsa stain on split skin smear
• Tissue biopsy
• PCR
• Leishmania skin test positive
Visceral leishmaniasis
• Stained smears of bone marrow aspirate, lymph node, spleen, liver
• Pancytopenia, hypoalbuminemia, hypergammaglobulinemia
• Leishmania skin test is negative

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 Rx
Cutaneous leishmaniasis- small lesions require no treatment
Visceral leishmaniasis-sodium stibogluconate, IV amphotericin B

Toxoplasmosis
 Intracellular protozoan toxoplasma gondii
 Definitive host - the cat
 Secondary hosts - humans, cattle, sheep,etc
 Modes of transmission -contaminated cat feces, undercooked infected meat, transplacental
infection
C/F
• Most are asymptomatic or trivial.
• Symptomatic pts - cervical lymphadenopathy, fever, myalgia, general malaise
• Severe - hepatitis, pneumonia, myocarditis, choroidoretinitis.
• Congenital toxoplasmosis- microcephaly, hydrocephalus, encephalitis, convulsions, mental
retardation, choroidoretinitis.
• Co infection with HIV
Dx
Serological dx -IgG antibodies detectable by Sabin Feldmam dye
Rx
Immunocompetant host - symptomatic rx
Severe disease - sulfadiazine, pyrimethamine for 4weeks with folic acid

Amoebiasis

Caused by entamoeba histolytica

Organism exist as both trophozoite and cyst
• Cyst - survives outside, in contaminated food and water
• Trophozoite- emerge from cyst and pass into the colon
C/f
• Asymptomatic
• Colitis
• Intrahepatic abscess -High swinging fever, profound malaise, Tender hepatomegaly
Complications - unusual...toxic mega colon, hemorrhage, stricture formation
Dx
• Microscopic examination of fresh stool or colonic exudate taken at sigmoidoscopy
Mobile trophozoite containing redblood cells are seen
• Amoebic flourescent antibody testing
Rx
• Metronidazole High doses for 5 days. -amoebic colitis
• Low doses adequate for hepatic abcesses
• After rx of Invasive disease, bowel cleared with luminal amoebicide
Prevention
• Hand hygiene
• Clean water
• Cysts are destroyed by boiling. Chlorine and iodine not very effective.

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Varicella (chickenpox)
 Herpesvirus, produces two distinct diseases: varicella / primary infection (chickenpox) and
herpes zoster / Reactivation (shingles).
 Most infections occurring in adulthood.
 Spread from the throat and from fresh skin lesions by air--borne transmission or direct
contact.
 The period of infectivity - from 2 days before the appearance of the rash until the skin
lesions are all at the crusting stage.
 Virus remains latent in dorsal root and cranial nerve ganglia.

 Clinical features of chickenpox - brief prodromal illness of fever, headache and malaise

Macules to papules to vesicles to pustules

Lesions occur on the face, scalp, and trunk and, to a lesser

extent, the extremities.
Pustules crust and heal without scarring.
 Complications include pneumonia, acute truncal cerebellar ataxia, and intrauterine infection
with structural damage to the fetus.
 The most common complication of shingles is post--herpetic neuralgia.
 Diagnosis by detection of VZV DNA within vesicular fluid, electron microscopy,
immunofluorescence or culture of vesicular fluid, and serology.
 Prevention and management - Chickenpox usually requires no treatment in healthy children
and infection results in life--long immunity.
Antiviral therapy with acyclovir or a similar drug may be
offered to patients over the age of 16 years.

Prophylactic ZIG is recommended for susceptible pregnant

women exposed to VZV.
Live attenuated varicella vaccine

Dengue

 The most common arthropod--borne viral infection in humans. A flavivirus.

 Four different antigenic serotypes of dengue virus are recognized and all are transmitted by
the daytime.
 Biting mosquito Aedes aegypti, which breeds in standing water in refuse dumps in inner
cities. Albopictus is a less common transmitter.
 Humans are infective during the first 3 days of the illness (viraemic stage)
 Heterotypic immunity between serotypes after the illness is partial and lasts only a few
months, although homotype immunity is life--long.
 The incubation period is 5–6 days.

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  Classic dengue fever - abrupt onset of fever, malaise, headache, facial flushing, retrobulbar
pain that worsens on eye movements, conjunctival suffusion and severe backache, which is
a prominent symptom. Lymphadenopathy, petechiae on the soft palate and transient,
morbilliform skin rashes.The fever has a biphasic or ‘saddleback’ pattern which is
characteristic.
 Severe dengue -arise from two or more sequential infections with different dengue
serotypes. It is characterized by the capillary leak syndrome, thrombocytopenia,
haemorrhage, hypotension and shock. It is characteristically a disease of children.
 dengue shock syndrome- abrupt onset of shock and haemorrhage into the skin and ear,
epistaxis, haematemesis and melaena which has a mortality of up to 44%.
 Management - supportive, analgesics,adequate fluid replacement. Corticosteroids are of no
benefit and convalescence can be slow. In DHF blood transfusion may be necessary.
 Prevention - sleeping under impregnated nets , topical insect repellents , adult mosquitoes
should be destroyed by sprays, and breeding sites should be eradicated.

Zika virus infection

 A flavivirus closely related to dengue viruses, an arbovirus, transmitted to humans by Aedes
mosquitoes.
 Fever, myalgia, eye pain, prostration and maculopapular rash, with spontaneous resolution.
 The WHO has also concluded that Zika virus is a trigger of the Guillain–Barré syndrome.

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  Accurate diagnosis of infection is complicated by serological cross--reactivity with dengue
viruses.

Infectious mononucleosis: Epstein–Barr virus infection

 Infectious mononucleosis (glandular fever), which occurs worldwide in adolescents and
young adults. EBV is transmitted in saliva and by aerosol.
Clinical features
 fever, headache, malaise and sore throat.
 Palatal petechiae and a transient macular rash are common
 Cervical lymphadenopathy, particularly of the posterior cervical nodes, and splenomegaly
are characteristic.
 Mild hepatitis is common, Clinical jaundice in 10% of young adults.
 myocarditis, meningitis, encephalitis, mononeuritis multiplex, cerebellar ataxia and
mesenteric adenitis are rare.
 Splenic rupture may occur in the first 3 weeks of illness and contact sport should be avoided
during this period.
 Severe, often fatal, infectious mononucleosis may result from a rare X--linked
lymphoproliferative syndrome affecting young boys.
 Those who survive have an increased risk of hypogammaglobulinaemia and/or lymphoma.
 EBV is the cause of oral hairy leucoplakia in AIDS patients and haemophagocytic
lymphohistiocytosis (HLH), a rare condition presenting with fever, rash, jaundice,
hepatosplenomegaly and enlarged lymph nodes.

Diagnosis

 EBV can be confirmed during the second week of infection by a positive Paul–Bunnell
reaction, which detects heterophile antibodies (IgM.False--positives can occur in viral
hepatitis, Hodgkin lymphoma and acute leukaemia.
 Specific EBV IgM antibodies indicate recent infection by the virus.
 Clinically similar illnesses - cytomegalovirus, toxoplasmosis and acute HIV infection (the so-
-called seroconversion illness).

Management
 The majority - no specific treatment.
 Corticosteroid therapy is advised when there is neurological involvement, marked
thrombocytopenia or haemolysis, or tonsillar enlargement.

Poliomyelitis
 Enterovirus species and result in acute flaccid paralysis (AFP).
 Polioviruses are excreted in faeces and spread via the faecal–oral route.
 They have a propensity for the nervous system, especially the anterior horn cells of the
spinal cord and cranial motor neurones.
Clinical features
 Incubation period is 7–14 days.

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  95% of individual is asymptomatic seroconversion.
 AFP, also known as paralytic poliomyelitis, arises in only approximately 0.1% and 1% of
infected children and adults, respectively. It follows about 4–5 days after an initial illness of
fever, sore throat and myalgia.
 Factors predisposing to the development of paralysis include male sex, exercise early in the
illness, trauma, surgery or intramuscular injection, and recent tonsillectomy (bulbar
poliomyelitis).
 Aspiration pneumonia, myocarditis, paralytic ileus and urinary
calculi are late complications of poliomyelitis.

Diagnosis
 All cases of AFP must be investigated to exclude poliovirus infection.
 Diagnosis is by detection of EV RNA in a throat swab, faecal sample or CSF, followed by
sequencing to identify precisely which EV is present.
Management
 Supportive - Bed rest, respiratory support with intermittent positive-pressure respiration is
required if the muscles of respiration are involved.
Prevention and control
 Improvements in sanitation, hygiene and the widespread use of polio vaccines.
 IPV has replaced OPV in the routine immunization schedules in many countries.

Rheumatic fever

 A multisystem disorder.

 Immune--mediated inflammatory disease as a result of infection with group A streptococci

(GAS).

 Affects the heart, skin, joints and CNS.

 Pharyngeal infection with GAS is followed and an autoimmune reaction triggered by

molecular mimicry between the cell--wall M proteins of the infecting Streptococcus
pyogenes and cardiac myosin and laminin.

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Management

 Infection should be eradicated with penicillin.

 The arthritis usually responds to non-steroidal anti--inflammatory drugs (NSAIDs)

 There is no good evidence that steroids are of benefit.

 Can largely be prevented by prophylaxis with daily oral or monthly intramuscular benzathine
penicillin until the age of 20 years or for 10 years after the latest attack.

 Erythromycin or clarithromycin is used if the patient is allergic to penicillin.

 More than 50% of those who suffer develop chronic rheumatic valvular disease,
predominantly affecting the mitral and aortic valves.

Rabies

 Rabies virus, a single--stranded RNA virus of the lyssavirus genus within the family of
rhabdoviruses.

 The virus is bullet--shaped and has spike--like structures arising from its surface containing
glycoproteins that cause the host to produce neutralizing, haemagglutination--inhibiting
antibodies.

 The virus has a marked affinity for nervous tissue and the salivary glands.

 2 major epidemiological settings: Urban rabies and Sylvan (wild)

Clinical features

 The incubation period is variable - few weeks to several years (avg it is 1–3 months)

 2 distinct clinical varieties of rabies are recognized

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 • Furious rabies – the classic variety.
- Pain and tingling at the site of the initial wound,Fever, malaise and
headache , anxiety and agitation or depressive features develop. Hallucinations, bizarre
behaviour and paralysis may also occur.
- Hyperexcitability, the hallmark of this.
- Hydrophobia (50% of patients)
- Aerophobia is considered pathognomonic.

• Dumb rabies – the paralytic variety.

- symmetrical ascending paralysis that resembles the GBS.

Diagnosis

 Generally, clinically.
 Skin--punch biopsies are used to detect antigen with an immunofluorescent antibody test on
frozen section.
 Viral RNA can be detected by genome amplification.
 Isolation of virus from saliva or the presence of antibodies in blood or CSF may establish the
diagnosis.
 Negri bodies are detected at postmortem in 90% of all patients with rabies.

Management

 Is symptomatic, as death is virtually inevitable.

 Drugs such as morphine, diazepam and chlorpromazine should be used liberally in patients
who are excitable.

Prevention and control

 Pre--exposure prophylaxis
 Post--exposure prophylaxis

 Domestic animals should be vaccinated.

 Wild animals in ‘at-­risk’ countries must be handled with great care.

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Bacterial meningitis

 The most common causes are Neisseria meningitidis (or meningococcus) and Streptococcus
pneumoniae, tuberculous, Haemophilus influenzae type b (Hib)

 Less common causes group B streptococci, Listeria monocytogenes, Staph. aureus and
Gram--negative bacilli.

Meningococcal sepsis

 carried asymptomatically in the nasopharynx of 5–20% of the general population.

 Meningococcal disease occurs when the bacteria invade the nasal mucosa and enter the
bloodstream.

Clinical features

 Classical triad of headache, fever and neck stiffness. Vomiting, diminished consciousness and
focal neurological signs.

 Blood stream infection - septic shock, such as fever, myalgia and hypotension, a petechial or
haemorrhagic rash, DIC and multiorgan failure.

Diagnosis

 Gram--negative diplococci may be seen on Gram stain of CSF or of aspirate from petechiae.

 meningococci can also be cultured from CSF or blood, or detected by PCR.

Management

 Sensitive to benzylpenicillin (in most cases), third--generation cephalosporins, and

chloramphenicol; cefotaxime or ceftriaxone.

 The meningococcal conjugate vaccine.

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  In an outbreak, close contacts should be given prophylaxis with oral rifampicin or
ciprofloxacin to eradicate the bacteria from the nasopharynx.

Gastroenteritis

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322
323
Invasive staphylococcal infection
Staphylococcal virulence factors

 Staphylococcal enterotoxin A
 Super antigenic staphylococcal exotoxins
 Toxic shock toxin 1
 Panton Valentine–leucocidin (PVL)

Methicillin--resistant Staphylococcus aureus (MRSA)

 Staph. aureus is commonly resistant to penicillin, and isolated resistance to other β--lactam
antibiotics, such as methicillin (now rarely used) and flucloxacillin

 Usually found as a skin commensal but can cause a variety of infections in soft tissues and
surgical wound infections.

 Eradication is difficult and people should be isolated from those at risk of significant
infection.

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  Topical decolonization is used to decrease bacterial load prior to invasive procedures.

 Careful attention to hand--washing and hygiene is the main method of controlling spread.

Staphylococcal scalded skin syndrome

 Caused by a toxin--secreting strain of Staph. Aureus

 Affects children under the age of 5.

 The toxin, exfoliating, causes intra--epidermal cleavage at the level of the stratum corneum,
leading to the formation of large, flaccid blisters that shear readily.

 It is a relatively benign condition and responds to treatment with flucloxacillin.

Toxic shock syndrome (TSS)

 Due to toxin--secreting staphylococci but toxin--secreting streptococci have also been

implicated.

 The exotoxin (normally toxic shock syndrome toxin 1, TSST--1) induces cytokine release,
causing abrupt onset of fever and shock, with a diffuse macular rash and desquamation of
the palms and soles.

 Many are severely ill and mortality is about 5%. Management is mainly supportive, although
the organism should be eradicated.

GU Infections

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Infection Pathogen Organs/ar Clinical features Clinical features in Complications Examination Investigations Management
eas In Men women
affected
Chlamydia Chlamydia Urethra Anterior Urethritis Increased vaginal
PID In women Diagnostic Doxycycline 100mg twice
trachomatis Endocervi Mucopurulent discharge Tubal infertility Mucopurulent Neucleic Acid daily *7days
x urethral discharge Dysuria Ectopic pregnancy cervicitis Amplification
Rectum worse on waking Postcoital or
Chronic pelvic pain and/or Tests(NAATs) If Doxy is contraindicated,
Pharynx with crusting at the Intermenstrual In pregnancy contact In Men pregnant or lactating-
Conjunctiv meatus bleeding Preterm birth bleeding FVU or US Azithromycin 1g stat ->
a Dysuria Lower abdominal Postpartum In women 500mg daily*2 days
Epydedymo- pain infections VVS(self-taken) or
orchitis Endometritis Neonatal ECS Abstinence for 7days/till
Acute Salphingitis
mucopurulent (Rectal or completion of tx.
conjunctivitis and Pharyngeal swabs) Sexual contact tracing,
Proctitis, Reactive Arthritis Pneumonia Notifying & Treating
Gonorrhoe Neisseria Urethra Anterior Urethritis Increased vaginal Epydedymo- In women Diagnostic Ceftriaxone 1g IM single
a gonorrhoea Endocervi Mucopurulent or discharge orchitis Mucopurulent NAATs dose
e x purulent urethral Dysuria PID /purulent In Men FVU or US
Rectum discharge (pofuse) Postcoital or GC Septicaemia cervicitis In women VVS(self- If confirmed susceptibility
Pharynx Dysuria Intermenstrual fever, and/or taken) or ECS Ciprofloxacin 500mg
Conjunctiv bleeding tenosynovitis,arthi contact single dose
a Lower abdominal tis, characteristic bleeding Culture
pain skin lesios with In Men US Hx of penicillin anaphylaxis
necrotic centres In women ECS or established
In pregnancy cephalosporin
Preterm birth Gram staining & allergy/pregnancy,
Postpartum Microscopy of Septinomycin 2g IM with
infections US/ECS Azithromycin 2g
Neonatal purulent Intracellular gram Or
conjunctivitis (-)ve diplococci Gentamicin 240mg IM
with Azithromycin 2g

Anbstinence for 7days/till

326
 completion of tx.
Sexual contact tracing,
Notifying & Treating.
Follow up assessment &
test of cure using GC NAAT
– 14 days after Rx

Non- C. Mucopurulent Microscopy of Gram First-line therapy-

gonococcal trachomatis urethral discharge stained urethral Doxycycline 100 mg twice
urethritis Mycoplasm worse on waking, secretion daily for 7 days
a crusting at the 5 or more
genitalium, meatus polymorphonuclear Anbstinence for 7days.
Ureaplasma Dysuria leucocytes per hPF
urealyticum, Discomfort or Sexual contact tracing,
Trichomona itching within the NAAT for N. Notifying & Treating.
s vaginalis, urethra gonorrhoeae, C.
Adenoviruse trachomatis and M. Follow-up is indicated only
s genitalium on an if CT or Mgen is confirmed
Herpes FVU sample or if symptoms persist
simplex
viruses
(HSV) 1 and
2

Non-
sexually
Transmitted
UTIs and

327
 strictures.

Recurrent Mycoplasm Azithromycin 1 g orally as

/persistent a a single dose,
NGU genitalium, followed by 500 mg daily
for 2 days
Persistent Trichomona with
or s vaginalis, Metronidazole 400 mg
recurrent twice daily for 5–7 days
symptoma
tic Mgen-positive and
urethritis macrolide-resistant/failed
occurring treatment with
30–90 days azithromycin,
following Moxifloxacin 400 mg daily
treatment for 10 days
of acute
NGU Test & treat Current sexual
partners.
Abstinence until both have
finished their treatment

328
PID C. upper Onset of Tubal infertility, mucopurulent Gram-staining of First-line treatment-
trachomatis genital symptoms often Ectopic cervical vaginal discharge, Ceftriaxone 1 g IM Single
N. tract occurs in the first pregnancy, discharge with Endocervical dose With
gonorrhoea endometri part of the Chronic pelvic pain contact Specimen Doxycycline 100 mg twice
e tis, menstrual cycle. bleeding, daily and
M. salpingitis, Lower abdominal Lower NAAT and culture Metronidazole 400 mg
genitalium tubo- pain, usually abdominal for N. gonorrhoeae twice daily
Anaerobes ovarian bilateral, tenderness, for 14 days
abscess, Increased vaginal adnexal and NAAT for C.
pelvic discharge, cervical trachomatis and M. Alternatives-
peritonitis Irregular bleeding, motion genitalium Ofloxacin 400 mg twice
Deep tenderness daily
dyspareunia, and
Dysuria Metronidazole 400 mg
twice daily for 14 days

Moxifloxacin 400 mg daily

for 14 days (first-line if the
patient is Mgen-positive)

Reviewed after 2-4weeks

Epididymo- Men under Pain, Unilateral scrotal Tenderness NAAT and culture Ceftriaxone 1 g IM Single
orchitis 35 years, swelling pain and swelling. and swelling for N. gonorrhoeae dose With
C. and Urethral discharge, of the Doxycycline 100 mg twice
trachomatis, inflammat Dysuria(often epididymis. NAAT for C. daily
N.gonorrhoe ion of the absent) Tenderness trachomatis and M. for 14 days
ae, Epididymi and swelling genitalium
M. s that can of the testicle If Mgen positive
genitalium extend with oedema Microscopy of Moxifloxacin 400 mg daily
into the and erythema Gram-stained for 14 days
Men over 35 Testis of the urethral secretions
years overlying (5 or more If UTI is the more likely
complicatio scrotal skin. polymorphonuclear diagnosis,

329
 n of a UTI leucocytes per Hpf, Ofloxacin 200 mg twice
Urethral Intracellular Gram- daily for 14 days
Mumps discharge negative
May be diplococcic-> GC) Anbstinence for 14days.
present Sexual contact tracing,
MSU if symptoms Notifying & Treating.
are suggestive of a Reassessed after 3 days.
UTI Reviewed after 4weeks

Bacterial Gardnerella Normal Increased vaginal BV in pregnancy, Creamy-white Microscopy of Gram Oral Metronidazole 400
vaginosis vaginalis, lactobacill discharge. Increased risk of homogeneous stained vaginal mg twice
(not Anaerobes, i- offensive fishy miscarriage and discharge, discharge. daily for 7 days
regarded Mycoplasm dominant odour preterm birth. slightly frothy
as a as, vaginal Increases the risk All three of the Metronidazole 2 g single
sexually Mobiluncus flora are of acquisition and following should be dose (less effective)
transmitte spp replaced transmission of present for the
d disease) by an HIV diagnosis to be Alternative topical
overgrowt made: treatments-
h of other • Characteristic Intravaginal
bacteria creamy-white Metronidazole 0.75% gel
homogeneous for 5 nights Or
vaginal discharge Intravaginal Clindamycin
• Raised vaginal pH 2% cream for 7 nights
of >4.5 (measured
using narrow-range
pH paper)
• Characteristic
fishy odour (which
can be released by
mixing the vaginal

330
 discharge with 10%
potassium
hydroxide).

Candidiasis Candida Vulval itching Transient penile In Women-> Microscopy of a For Females-
albicans, Increased thick, irritation and rash Vulval Gram-stained Oral triazole drugs-
Candida white vaginal immediately erythema vaginal smear, or a Fluconazole 150 mg as a
glabrata discharge following sex Fissuring and subpreputial smear single dose
Vulval burning Persistent oedema. (fungal Itraconazole 200 mg twice
External dysuria balanoposthitis Typical white, pseudohyphae and daily for 1 day
Superficial curdy, spores)
dyspareunia adherent Clotrimazole pessary 500
plaques on the Culture of vaginal, or mg as a single dose
vaginal walls subpreputial, swabs Miconazole vaginal ovule
1.2 g as a single dose
In Men-> Diabetes should be Econazole pessary 150 mg
Erythema of excluded in men nightly for 1–3 nights
the foreskin with severe Supplemented with
and glans balanoposthitis antifungal cream applied
penis. to the vulva.
Spotty, red,
itchy rash on For C. glabrata and other
the glans, with non-albicans-
an Nystatin pessaries 200 000
accumulation units nightly for 14 nights

331
 of white
discharge In pregnancy-
under the oral therapies should not
foreskin. be used
Fissuring and
phimosis of For Males-
the Oral therapy
foreskin(sever or topical antifungal cream
e)
Recurrent candidiasis-
Weekly oral Fluconazole
150 mg, or
Clotrimazole pessary 500
mg, for up to 6 months
Trichomoni Trichomona In Urethral discharge, Increased In pregnancy- Vulval Phase-contrast Metronidazole 400 mg
asis s vaginalis women- Irritation, purulent Increased risk of erythema. microscopy of twice daily for 7 days
vagina and Dysuria vaginal discharge, preterm birth and Inflamed vaginal discharge Single-dose Metronidazole
urethra Malodour, low birth weight. vaginal 2 g (less effective)
Vulval pruritus, mucosa Culture
In Men- External dysuria, Increases the risk Yellow or grey Resistant to metronidazole
urethra Dyspareunia of acquisition of and frothy Diagnostic- and other Nitroimidazole-
and HIV discharge NAATs High-dose Metronidazole
subpreput VVSs in women or Tinidazole
ial sac Cervix may FVU in males
have multiple Abstinence from sex for at
small least 7 days.
haemorrhagic Sexual contacts should be
areas- notified, tested and
‘strawberry treated
cervix’

332
Anogenital Human Anogenita First appear at sites Warts tend to Warts on HPV testing is not The choice of treatment
warts papillomavir l warts of trauma during increase in size mucous appropriate. depends on the number,
us types 6 Laryngeal sex. and number membranes- type and distribution of
and 11 papilloma In women- during pregnancy Soft and non- Atypical lesions lesions.
tosis (In In males- Fourchette -> or in keratinized should be biopsied.
Neonates) Prepuce and glans- vulva and immunosuppresse For non-keratinized warts-
> urethra and perineum d patients Investigations Topical Podophyllotoxin
down the penile On the hair- should include NAAT (0.5% solution or 0.15%
shaft. bearing skin- for N. gonorrhoeae cream) twice daily for 3
Firm and and C. trachomatis, consecutive days per
keratinized and serology for week. (Contraindicated in
syphilis and HIV, as Pregnancy)
co-infection with
other STIs is For keratinized warts-
common Cryotherapy
Electrocautery

For both-
Imiquimod 5% cream
daily, Three times a week.
(Contraindicated in
Pregnancy)

Use of condoms
Follow-up

333
Molluscum Molluscum labia Small (typically 2–5 mm in diameter), Diagnosis is made on Often self-limiting.
contagiosu contagiosu majora, benign, smooth papules with the characteristic
m m penile central umbilication clinical appearance. Cryotherapy
shaft, Podophyllotoxin cream
A DNA virus pubic Investigations for Imiquimod cream
region, other STIs
lower Discourage from shaving
abdomen, or
upper waxing the pubic hair
inner
thighs

Lymphogra Invasive Primary lesion- ‘Groove NAAT for C. First-choice treatment-

nuloma serovars, L1, Painless papule or Shallow ulcer sign’ due to trachomatis- Doxycycline 100 mg twice
venereum L2 and L3, of appearing at the area of inoculation, the inguinal Swab taken from the daily for 21 days or
Chlamydia 7–30 days after exposure. ligament genital ulcer base, or Erythromycin 500 mg four
trachomatis separating the from the rectal times daily for 21 days.
Proctitis with symptoms of rectal pain, two enlarged mucosa
mucopurulent discharge, rectal bleeding, lymph node Abstain from sex until
constipation and tenesmus systems If positive-. completion of treatment.
Genotyping for LGV
Fever and malaise Sexual contacts should be
Testing for the other notified, examined, tested
Secondary lesions- causes of genital and treated.
Enlarged, tender regional lymph nodes ulcers
(usually Unilateral and affect the inguinal Follow-up should continue
and femoral nodes) until all symptoms and
Nodes may become matted with bubo signs have resolved(3–6
formation, which may rupture. weeks)

Tertiary stage-
Chronic inflammatory response with
tissue destruction.

334
 In the rectum, cause fistulae, strictures
and
granulomatous fibrosis(mimicking
Crohn’s disease)
Scarring of the genital area.
Destruction of local lymph nodes
Genital lymphoedema

Chancroid Haemophilu In men- Tender papules develop at the site of PCR for H. ducreyi Single-dose regimens-
s ducreyi prepuce inoculation-> DNA (But no Ceftriaxone 250 mg IM Or
and glans Rupture into Painful, ragged-edged commercial assays Azithromycin 1 g orally
penis ulcers with necrotic bases that bleed available)
easily. Multiple-dose regimens-
In women- Testing for the other Ciprofloxacin 500 mg
labia Painful inguinal lymphadenopathy, can causes of genital twice daily for 3 days Or
minora develop into large buboes that ulcers. Erythromycin 500 mg four
and suppurate. times daily for 7 days.
fourchette NAAT for N. (Multiple-dose regimens
gonorrhoeae and C. should be used in HIV
trachomatis on FVU, patients)
or a VVS
Anbstinence for 7days.
Serology for HIV Follow up at 3–7 days

335
Donovanos Klebsiella Nodules at the site of inoculation-> Giemsa or Silver Azithromycin 1 g weekly
is/ granulomati Friable, non-painful ulcers Or stains- or 500 mg daily Or
Granuloma s Hypertrophic lesions that increase in Presence of Doxycycline 100 mg twice
inguinale size. Donovan bodies in daily for a minimum of 3
scrapings or biopsies weeks and until the lesions
Enlargement of the inguinal lymph of the lesions. have healed.
nodes, which may ulcerate. (Donovan bodies are
the encapsulated Abstain from sex for at
intracellular Gram- least 3 weeks.
negative rods of K.
granulomatis visible Followed up until the
within mononuclear lesions have fully resolved.
cells)

Screening for all

other STIs
Pediculosis Phthirus Pubic and Itch due to hypersensitivity to the louse Lice may be Screening for other Permethrin 1% should be
pubis pubis coarse bites seen on the STIs left on for 10 minutes.
(pubic body hair, pubic and Malathion 0.5% should be
louse) eyelashes body hairs. left on for 12 hours
and
eyebrows Resemble Second application after 7
small scabs or days
freckles.
(Permethrin is safe in
Eggs (nits) are pregnancy)
laid at the hair
base and are Sexual partners should be
strongly examined and treated if
adherent to infected.
the hairs

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Syphilis Treponema Acquired syphilis Dark-ground microscopy of Early syphilis (primary,
pallidum Primary syphilis secretions from a primary secondary and early
Between 9 and 90 days (mean 21 days) after exposure. chancre or condylomata lata. latent)
Papule develops at the site of inoculation. -> • Benzathine penicillin G
Ulcerates to become a painless, firm ulcer (chancre). Screening- 2.4 MU i.m. single dose.
Painless regional lymphadenopathy. Treponemal enzyme In penicillin allergy:
immunoassay (EIA) to detect • Doxycycline 100 mg
Secondary Secondary syphilis IgG and IgM twice daily for 14 days.
syphilis With untreated primary syphilis.
hepatitis, Between 6 and10 weeks after the appearance of the primary lesion. If above is positive- Late latent,
nephritis, Constitutional symptoms, including fever, sore throat, malaise and Treponemal tests cardiovascular and
arthritis, arthralgia. T. pallidum gummatous syphilis
meningitis, haemagglutination • Benzathine penicillin G
uveitis, Widespread skin rash involving the whole body, including the palms Assay(TPHA) 2.4 MU i.m. three doses at
interstitial and soles- non-itchy, maculopapular rash that may have a coppery T. pallidum particle weekly intervals.
keratitis, colour. agglutination Assay(TPPA) In penicillin allergy:
retinal Generalized lymphadenopathy. (Highly specific but remains • Doxycycline 100 mg
involvemen Condylomata lata (moist, wart-like plaques found in the perianal area positive for life; unable to twice daily for 28 days.
t and other moist body sites) differentiate between prior
Mucosal lesions in the mouth and on the genitalia presenting as treated infection and re- Neurosyphilis
distinct mucous patches or becoming confluent to form ‘snail-track infection.) • Procaine penicillin 2.4
ulcers’. MU i.m. daily plus
Non-treponemal tests probenecid 500 mg orally
Latent syphilis Venereal Disease Research four times daily for 14
Early latent(within 2 years of infection acquisition) Laboratory (VDRL) days.
Late latent(present for 2 or more years) Rapid Plasma Reagin (RPR) In penicillin allergy:
(Can be used to monitor • Doxycycline 200 mg
Tertiary syphilis treatment response and twice daily for 28 days.
Within 2–30 or more years of contracting the infection. evidence of re-infection)
Gummatous syphilis - skin and bones/ any organ
Cardiovascular syphilis-> aortitis, aortic regurgitation, aneurysm of the Examination of the
ascending aorta and stenosis of the coronary artery ostia. cerebrospinal fluid (CSF) for
Neurosyphilis-> chronic meningovascular damage, endarteritis of the evidence of neurosyphilis

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small vessels of the brain and spinal cord, ‘general paralysis of the
insane’, tabes dorsalis

Congenital syphilis
Early (diagnosed within the first 2 years of life)
rash, condylomata lata, mucous patches, nasal discharge,
hepatosplenomegaly, periostitis
Late (diagnosed over the age of 2)
Neurological or gummatous lesions,
Stigmata of congenital syphilis(Hutchinson’s teeth, sabre tibia,
bossing of the frontal and parietal bones, and saddle nose)

Syphilis in pregnancy Pregnancy

Early syphilis • Penicillin can be safely
Second-trimester miscarriage or stillbirth used in pregnancy but
Preterm birth before 32 weeks’ gestation doxycycline should not be
Neonatal death used.
Congenital syphilis
Those being treated for
early syphilis should
abstain from sex for at
least 14 days.
Sexual contacts must be
traced and investigated.

Regular follow-up within

the first year using repeat
VDRL/RPR titres to
establish the ‘four-fold
fall’.

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Genital Herpes Initial episode Neurological Ulcers HSV DNA Initial episode-
herpes simplex Primary genital Primary genital complications- may be detection Saltwater bathing,
virus type 1 infection- infection- aseptic present using PCR on Sitting in a warm bath,
or type 2 Multiple painful, shallow External meningitis, on the a swab Topical anaesthetics
ulcers, dysuria and autonomic cervix taken from
Tender inguinal vulval pain, neuropathy the ulcer. Aciclovir 400 mg three times daily*5 days
lymphadenopathy, leading to urinary (Drug of choice in pregnancy & Breast
Fever, myalgia and retention Tests for feeding) Or
headache other STIs. Valaciclovir 500 mg twice daily*5days Or
Increases the Famciclovir 250 mg three times daily*5 days
Non-primary acquisition and Blood tests
genital infection- same transmission of for HSV Avoid sex during the prodrome and
Milder illness HIV type-specific recurrences.
more likely to be antibodies. (Disclosure should be advised
asymptomatic in all relationships)

Recurrent genital herpes- Recurrence-

Prodrome of tingling, same Saltwater bathing,
itching or pain in the area Topical anaesthetics

Episodic treatment
(When recurrences are infrequent but
severe)
Aciclovir 400 mg three times daily*5 days Or
Famciclovir 250 mg three times daily*5 days
Or
Aciclovir 800 mg three times daily for 2 days
Or
Famciclovir 1 g twice daily for 1 day Or
Valaciclovir 500 mg twice daily for 3 days

Suppressive treatment
(For those with six or more recurrences per

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year)
Aciclovir 400 mg twice daily Or
Valaciclovir 500 mg daily Or
Famciclovir 250 mg twice daily
for a maximum of 12 months

In pregnancy
Initial episode of HSV in the third trimester-
Aciclovir 400 mg three times daily until
delivery

Initial episode of HSV in the first or second

trimester-
Daily suppressive Aciclovir from 36 weeks’
gestation

Caesarean section should be the

recommended mode of delivery

Recurrent HSV-
Daily suppressive Aciclovir from 36 weeks’
gestation.
Caesarean section is not indicated.

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