AMK diseases

septicaemia
• History: Ask about respiratory/GI/GU symptoms, any travel or immuncomp?
Signs: High T or low. High pulse. High Resp rate. Low BP e.g. ≤90/70 mm/hg, look for localised signs.
Tests: Culture all possible sources if possible before treatment e.g. blood/sputum. Save serum for
virology. MSU/dipstick.
Prognosis: Poor if very old/young. Low bp/wcc/PaO2, DIC, hypothermia
Treatment: Get help e.g. if no access to IV lines. Antibiotics must be up and running within an
hour of tell-tale signs of serious sepsis. Follow local guidelines. Suspect MRSA. Change antibiotics in
light of sensitive's. Give drugs IV (over ≥5 mins) if severely ill (eg for ~2days, then change to PO if
possible) If in doubt ask infection specialist.
Medications: UTS: co-amoxiclav IV + gentamicin IV once daily. Intra-abdominal sepsis:
Ceftazidime IM/IV + metronidime IVI. Meningococcal sepsis: Cefotaxime. With neutropenia:
Tazocin IVI + gentamicin
Meningitis
 Meningitis continued…
• When to act: headache, high temp, neck stiffness, altered mental state: if any 2 co-exist, give
benzylpenicillin, IM/IV, before admitting.
• Organisms: meningococcus or pneumococcus
• Differential: Malaria, encepthalitis, CMV, septicaemia, subarachnoid, dengue, tetanus.
• Features: Early: Headache/leg pains/cold hands + feet/abnormal skin colour. Later:
Meningism: Neck stiffness/photophobia/kernig’s sign (pain + resistance on passive knee
extension with hip fully flexed). Low conscious level, coma. Seizues +/- focal CNS signs +/-
opisthotunus. Petechical rash. Signs of disease causing: zoster/cold sore/genital vesicles/ (HSV)/
HIV signs e.g(candidiasis, dermatitis)/bleeding +/- red eye/mumps/sore throat +/- jaundice +/-
nodes/spelnectomy scar
• Signs of galloping sepsis: Slow capillary refill/DIC/low BP, T/pulse High or normal.
• Management: <55yrs cefotaxime slow IV, 55> as on the left + ampicillin. Aciclovir if viral
encephalitis suspected. If ICP raised, summon help from neurosurgeons. Prophylaxis: household
contacts in droplet range/those who have kissed pts mouth= Give rifampicin PO
measles
 Measles continued
• Signs: (pre-eruptive): malaise/fever/rhinorrhea/cough/conjunctivial suffusion/koplik’s
spots(found mostly opp 2nd molar tooth). (eruptive). Rash that spreads initially on the
face(forehead mainly), spreading rapidly to rest of the body. Initially the rash is discrete but may
become confluent & patchy especially on the face &neck. Fades within a week leaving a brown
discoloration.
• Diagnosis: Detection of measles specific IgM in blood/oral fluid/genome/antigen
detection/throat swabs
• Treatment: Supportive eg painkillers. Antibiotics only when secondary bacterial infection
occurs.
Mumps
 Mumps continued…

• Cause: Infection with paramyxovirus-droplet spread

• Signs/symptoms: Fever/malaise/headache/anorexia usually followed by severe pain over
the paratoid glands with either unilateral or bilateral swelling. Trismus (spasm of jaw) due to pain
is common at this stage.
• Complications: CNS involvement most common. 5% of pts develop meningitis. Epididymo-
orchitis develops in 1/3 of post pubertal pts(sterilisation in a small number).
Pancreatitis/oophoritis/myocarditis/mastitis/hepatitis/polyarthritis
• Diagnosis: mostly done by signs/symptons. When in doubt: serological demonstrations of
mumps-specific IgM response in acute blood/oral fluid.
• Treatment: supportive. Attention should be given to adequate nutrition and mouth-care.
Analgesics for pain relief.
 Asthma
Characterised by recurrent episodes of dyspnoea/cough/wheeze caused by reversible airways obstruction- this is caused by: bronchial muscle contraction. Stimuli:
mucosal swelling/inflammation caused by mast cell & basophil degranulation releasing inflammatory mediators hence ↑ mucous production.

Symptoms: intermittent dyspnoea/wheeze/cough/sputum. Ask about precipitants: cold

air/exercise/emotion/allergens/smoking(or passive)/pollution/B blockers/NSAIDS. Diurnal variation in symptoms or peak flow.
Quantify exercise tolerance. Disturbed sleep(quant as nights per week-sign of severe asthma). Acid reflux: 40-60% asthma pts
have it. Other atopic disease: family history/eczema/hay fever. Home: pets? carpet? feather pillow? soft furnishing? Job: some
jobs may exacerbate eg paint sprayers/food processors.

Signs: Tachypnoea/audible wheeze/hyperinflated chest/hyperresonant percussion note/diminished air entry/polyphonic

wheeze. Severe attack: inability to complete sentences/pulse>110bpm/respiratory rate >25/min/PEF 33-50% of predicted. Life
threatening attack: silent chest/cyanosis/bradycardia/exhaustion/PEF <33% predicted/confusion/feeble respiratory effort.

Tests: Acute attack: PEF/sputum culture/FBC/U&E/CRP/blood cultures/. ABG analysis shows normal/slightly reduced PaO2 &
low PaCO2 (hyperventilation). If PaO2 normal but pt is hyperventilating, watch carefully & repeat ABG a little later. If PaC02
raised, transfer to high dependency unit/ITU for ventilation(failing resp effort) CXR to exclude infection/pneumothorax. Chronic
asthma: PEF monitoring. Spirometry obstructive defect. Usually ≥15% improvement in FEV1 following B2 agonists/steroid trial.
CXR: hyperinflation. Skin-prick tests to ID allergens.

Treatment: Acute: salbutamol + ipratropium bromide nebulized with 02. 40-60% O2 (careful if COPD to prevent
hypercapnia) Hydrocortisone IV or prednisolone PO or both if very ill. CXR to exclude pneumothorax. In life threatening
situations= Inform ITU & seniors. Add magnesium sulphate IV. Give salbutamol nebulizers. Monitor ECG for arrhythmias. If
improving: 40-60% 02. Prednisolone PO continue course. Nebulized salbutamol. Monitor peak flow & O2 saturations. If no
improvement after 15-30mins: Continue 100% O2 & steroids. Hydrocortisone IV or prednisolone PO if not already given. Give
salbutamol nebulizers continuously. Continue ipratropium.
Asthma- carried on
• Treatment Acute: Monitoring the effects of treatment: Repeat PEF 15-30min after initiating
treatment. Pulse oximeter: Maintain SaO2 >92%. Check blood gases if initial PaCO2 was normal/raised/pt
deteriorating. Record PEF pre & post B agonist at least 4x in hospital. Once Pt is improving: wean down &
stop aminophylline slowly. Reduce nebulized salbutamol & switch to inhaled B agonist. Initiate inhaled
steroids & stop oral steroids if possible. Continue monitoring PEF, look for deterioration on reduced
treatment. Look for cause of the acute exacerbation and admission.

• Behaviour: Help quit smoking/avoid precipitants/check inhaler technique/teach use of peak flow meter to
monitor PEF 2x daily. Educate on meds in light of symptoms & how to adjust.
 Asthma- chronic

Affects 5-8% of population. Characterized by recurrent episodes of dyspnoea, cough and wheeze caused by
reversible airway obstruction. 3 factors contribute to narrowing: bronchial muscle contraction, triggered by a
variety of stimuli; mucosal swelling/inflammation, caused by mast cell & basophil degranulation resulting in release
of inflammatory mediators- increased mucus production. Symptoms: intermittent dyspnoea, wheeze, cough (often
nocturnal) and sputum. Ask specifically about: precipitants: cold air, exercise, emotion, allergens (house dust mite,
pollen, fur) infection, smoking & passive smoking, pollution, NSAIDs and B-blockers. Diurnal variation: in symptoms
and peak flow. Marked morning dipping of peak flow is common & can tip balance into a serious attack, despite
having normal peak flow at other times. Exercise: Quantify exercise tolerance. Disturbed sleep: quantify as nights
per week (sign of severe asthma). Acid reflux: 40-60% of those with asthma have reflux; treating it improves
spirometery but not necessarily symptoms. Other atopic disease: eczema, hay fever, allergy/family history. Home
(especially bedroom): pets? Carpet? Feather pillows or duvet? Floor cushions and other ‘soft cushions’? Job: if
symptoms remit at weekends or holidays, work may provide trigger (15% of cases are work-related- more for paint
sprayers, food processors, welders and animal handlers). Ask pt to measure peak flow at intervals at work and home
to confirm this. Signs: tachypnoea; audible wheeze; hyper-inflated chest; hyper-resonant percussion note; air entry
↓; widespread, polyphonic wheeze. Severe attack: inability to complete sentences; pulse >110bpm; resp rate
>25/min; PEF 33-50% predicted. Life-threatening attack: silent chest, confusion; exhaustion; cyanosis; bradycardia;
PEF <33% predicted. Near fatal: ↑PaCO2. Tests: acute attack: PEF, sputum culture, FBC, U&E, CRP, blood cultures.
ABG analysis usually shows a normal or slightly ↓PaO2 but PaCO2 ↓(hyperventilation). If PaO2 is normal but pt
hyperventilating, watch carefully & repeat ABG a little later. -> if PaCO2 normal/raised transfer to ITU for ventilation
as this signifies failing resp effort. CXR to exclude infection/pneumothorax. Chronic asthma: PEF monitoring.
Spirometry obstructive defect. Usually ≥15% improvement in FEV1 following B2 agonists/steroid trial. CXR:
hyperinflation. Skin-prick tests to ID allergens.
 Asthma- chro nic con tinued…

Management: Behaviour: quit smoking, avoid precipitants. Check inhaler technique. Monitor PEF 2x a day. 1)
occasional short-acting inhaled B2 agonist if used more than once daily or night time go to 2. 2) add standard-dose
inhaled steroid e.g. beclometasone 3) add long-acting beta agonist e.g. salmetrol if benefit but still inadequate
control, ↑dose for beclometasone- if no effect of Beta2-agonist stop it. Review diagnosis. Leukotriene receptor
antagonist/oral theophylline may be tried. 4) consider trials of beclometasone, modified-release oral theophylline;
modified-release oral B2-agonist; oral leukotriene receptor atangonist it conjunction with previous therapy. 5) oral
prednisolone. Continue with high-dose inhaled steroids. Drugs: B2-agonists relax bronchial smooth muscle
(↑cAMP). Best given by inhalation but may also be given PO/IV. SE: tachyarrhythmia's, ↓K+, tremor, anxiety. Long-
acting inhaled B2 agonist can help nocturnal symptoms & reduce morning dips- they may be alternatives to
↑steroid dose when symptoms are uncontrolled, SE: as salbutamol, paradoxical bronchospasm. Corticosteroids:
best inhaled to minimise SE’s e.g. beclometasone, may also be given IV/PO. Act over days to ↓bronchial mucosal
inflammation. Rinse mouth after inhaled steroids to prevent oral candidiasis. Oral steroids used acutely and longer
term in lower dose if control is not optimal on inhalers. Aminophylline (metabolised to theophylline) acts by
inhibiting phosphodisterase, thus ↓bronchoconstriction by ↑cAMP levels. Try as prophylaxis, at night PO to prevent
morning dip. Also useful as adjunct if inhaled therapy is inadequate- in acute severe asthma it may be given IVI. Has
narrow therapeutic ratio causing arrhythmias, GI upset and fits in toxic range. Check theophylline levels & do ECG
monitoring & check plasma levels after 24h if IV therapy used. Anticholinergic’s e.g. ipratropium may ↓muscle
spasm synergistically with B2-agonists but are not recommended in current guidelines for chronic asthma- may be
more of benefit in COPD. Cromoglicate may be used as prophylaxis in mild & exercise-induced asthma (always
inhaled) esp in children- may precipitate asthma. Leukotriene receptor antagonists e.g. oral montelukast block
effects of cysteinyl leukotriene's in airways by antagonizing the cystLT1 receptor. Anti-IgE monoclonal antibody
omalizumab may be of use in highly selected pts with persistent allergic asthma. Given as subcutaneous infections
every 2-4w depending on dose.
 C OP D

Wider chest Pink Puffer Blue bloater

 COPD continued…
Definition: a common progressive order characterized by airway obstruction (FEV1 <80% predicted) with little/no
reversibility. It included chronic bronchitis & emphysema. Usually patients have COPD or asthma, not both.
Favoured by: age of onset 35yrs>, smoking (passive/active), pollution related. Chronic dyspnoea, sputum production.
Diurnal variation of FEV1. Chronic bronchitis is defined clinically as a cough with sputum production on most days for 3
months, 2 years consecutively. Emphysema defined histologically as enlarged airway spaces distal to terminal
bronchioles, with destruction of alveolar walls.
Prevalence: 10-20% of over 40s
Pink puffers: They have- ↑alveolar ventilation, near normal PaO2 and a normal/low PaCO2. Breathless but not
cyanosed. May progress to type 1 respiratory failure (hypoxia) (type 2 is hypoxia & hypercapnia). Blue bloaters: They
have- ↓alveolar ventilation rate with low PaO2 and a high PaCO2. Cyanosed but not breathless & may go onto develop
cor pulmonale. Their respiratory centres are relatively insensitive to CO2 & rely on hypoxic drive to maintain
respiratory effort.
Symptoms: Cough, sputum, wheeze, dysponea. Signs: Tachypnoea, use of accessory muscles of respiration,
hyperinflation, ↓cricosternal distance, ↓expansion, resonant/hyperresonant percussion note, quiet breath sounds,
wheeze, cyanosis, cor pulmonale.
Complications: acute exacerbations +/- infection, polycythaemia (cause: hypoxia), respiratory failure, cor pulmonale,
pneumothorax, lung carcinoma.
Tests: FBC, PCV ↑, CXR: hyperinflation, flat hemidiaphragms, large central pulmonary arteries, ↓peripheral vascular
markings,bullae. ECG: right atrial & ventricular hypertrophy. ABG: PaO2 ↓ +/- hypercapnia. Lung function: obstructive
+ air trapping.
 COPD (continued…)
Management
• Bronchodilators
• B-Adrenergic agonists. Many pts with mild COPD feel breathless after inhaling a B-adreneregic agonist such as salbutamol. In more severe COPD, a
long-acting B2 Agonist should be used e.g. foramoterol powder inhaled or salmetrerol. Indacaterol daily is also effective.
•  Antimuscarinic drugs. More prolonged & greater bronchodilation is achieved with antimuscarinic agents: tiotropium (long-acting) or ipratropium.
 Phosphodieterase type 4 inhibitors- Roflumilast is an inhibitor with anti-inflammatory properties. It is used as an adjunct to bronchodilators for the
maintenance treatment of COPD patients.
•  Corticosteroids- Airway function may improve considerably. Prednisolone should be given, with measurement of lung function before/after
treatment. If there is objective evidence of substantial degree of improvement (FEV 1 >15%) prednisolone should be discontinued and replaced by
inhaled corticosteroids (beclometasone, adjusted according to response). Combination of corticosteroid with long-acting B2 agonist may protect
against lung function but does not improve overall mortality. High-dose inhaled steroids are not advised are they cause increased rates of respiratory
infection.
•  Antibiotics- Prompt antibiotic treatment shortens exacerbations and should always be given in acute exacerbations to prevent hospital admission &
further lung damage. Pts can be given antibiotic at home to start soon as sputum turns yellow/green. Cefixime
•  Antimucolytic agents – reduce sputum viscosity & can reduce no. of acute exacerbations. Carbocystein can be tried.
•  Diuretic therapy- necessary for all oedematous pts. Daily weights should be recorded.
•  O2 therapy- shown substantial improvement in survival rates especially if O 2 given over 19 hours/daily- shown reduce in pulmonary artery pressure.
Should be given to pts with PaO2 of <7.3 kPa/nocturnal hypoxia (main cause of death- arrhythmias) / pulmonary hypertension/ peripheral edema.
•  Other measures
• Annual influenza vaccine
• Alpha1- antitrypsin replacement
• Heart failure treatment
• Venesection due to secondary polycythaemia
• Promethazine 125mg daily to treat breathlessness feeling.
• Surgery
 Pneumothorax

Collapsed lung is of darker shade

 Pneumothorax (collapsed lung) continued…
Causes: often spontaneous (especially in young thin men) due to rupture of a sub-pleural
bulla. Other causes: COPD, asthma, TB, pneumonia, lung abscess, carcinoma, cystic fibrosis,
lung fibrosis, sarcoidosis, connective tissue disorders (marfans etc), trauma, iatrogenic.

Clinical features symptoms: There may be no symptoms especially if fit and young. Sudden
onset of dyspnea and/or pleuritic chest pain. Patients with asthma/COPD may present with
sudden deterioration. Mechanically ventilated pts may present with hypoxia or an increase in
ventilation pressures. Signs: reduced expansion, hyper-resonance to percussion & diminished
breath sounds on the affected side. With a tension pneumothorax, the trachea will be
deviated away from the affected side.
Test: CXR if tension pneumothorax suspected as it will delay necessary treatment. Otherwise
request an expiratory film & look for area devoid of lung markings, peripheral to edge of
collapsed lung. Ensure the suspected pneumothorax is not a large emphysematous bulla.
ABG in dyspnoeic pts & those with chronic lung disease.

Management: Pneumothorax due to trauma/mechanical ventilation requires a chest drain.

Hemothorax
Affected lung is of white shade
 Hemothorax continued…
What it is: Blood in the pleural space associated with both haemorrhagic shock and respiratory compromise. Must
be effectively evacuated to prevent complications such as fibrothorax and empyema.
Tests: CXR (upright- ASAP)- shows hemothorax large enough to obscure the costophrenic selcus or is associate with
pneumothorax.
Treatment: Initial treatment directed to cardiopulmonary stabilisation & evacuation of pleural blood collection. Pt
should be sitting upright unless contraindicated. Administer O2+reassess ABC. If pt hypotensive, establish large-
bore IV line. Immediately start fluid ressus (lactated ringer solution), including blood transfusion if needed.
Evaluate for possible tension pneumothorax- needle decompression may be needed if it is the case. Chest tube for
asymptomatic pt is unclear but if pt has any respiratory distress, perform thoracostomy. If a conventional chest
tube not draining blood further steps may be needed- Add a second, if ineffective, perform thoracotomy. Need
aspiration contraindicated if clotting deficiencies are present- perform thoracostomy with ability to visualise &
control any bleeding that occurs.
Surgical exploration in cases of traumatic haemothorax should be performed if: Evacuation of more than 1000mL
of blood after tube thoracostomy (massive haemothorax), continued bleeding from chest (150-200 mL for 2-4hrs),
repeated blood transfusion.
Complications: residual clot, infected collections, trapped lungs- late sequels requiring surgical intervention.
Retained clot (more than 500ml undrained collection) is a well known sequela after tube thoracostomy for
hemothorax- should be evacuated early. Empyema (puss-filled pleural cavity) usually develops superimposed
infection in a retained collection of blood- requires surgical drainage & possibly decortication. Fibrothorax is a late
uncommon complication that can result from retained hemothorax-horacotomy & decortication are required for
treatment.
 Pleurisy (infection of pleura)

Pleurisy is due to inflammation of the pleura caused by infection by coxsackie B

virus. Who are affected: Most likely young adults, during late summer and
autumn.
Other causes: anything which can inflame the pleura- pneumonia, blood clots in
lung (pulmonary embolism), Pneumothorax, lung cancer and some sort of
arthritis.
Signs & symptoms: Upper respiratory tract illness followed by pleuritic pain in the
chest & upper abdomen with tender muscles. Pleuritc pain results which is a
sharp ‘stabbing’ pain in a part of the chest- usually made worse when breathing
when breathing/coughing.
Tests: CXR- most likely remains normal.
Treatment: Painkillers, illness usually clears within a week.
Complications: Pain that does not ease/develops slowly, breathing difficulties,
coughing up blood, any other unsure symptoms.
Pulmonary embolism
 Pulmonary embolism (blood clot)
Causes: Venous thrombosis in pelvis/legs. Clots break off & pass through veins & right side of heart before lodging in
pulmonary circulation. Rare causes: right ventricular thrombus, septic emboli (right-side endocarditis), fat, air, amniotic fluid
embolism, neoplastic cells, parasites.
Risk factors: Recent surgery especially abdominal/pelvic/hip/knee replacement, thrombophilia e.g. antiphospholipid, leg
fracture, prolonged bed rest/reduced mobility, malignancy, pregnancy/postpartum, previous PE.
Clinical features: depend on number/size/distribution of emboli- small emboli may be asymptomatic whereas large is often
fatal. Symptoms: Acute breathlessness, pleuritic chest pain, haemoptysis(coughing up blood), dizziness, syncope (temp loss
of consciousness). Ask about risk factors, past/family history, family history of thromboembolism. Signs: Pyrexia, cyanosis,
tachypnoea, tachycardia, hypotension, raised JVP, pleural rub, pleural effusion. Look for signs of a cause e.g. DVT.
Tests: FBC, baseline clotting, D-dimers. ABG may show a ↓PaO2 & ↓PaCO2. CXR: may be normal or show oligaemia
(decreased volume of blood) of affected segment, dilated pulmonary artery, linear atelectasis, small pleural effusion, wedge-
shaped opacities/cavitation(rare). ECG may be normal or show tachycardia, right bundle branch block, right ventricular
strain. CT pulmonary angiography (CTPA) is sensitive and specific in determining if emboli are in pulmonary arteries.
Management: anticoagulant with LMW heparin. Start warfarin. Stop heparin when INR>2 & continue warfarin for a min
3months. Consider placement of vena cava filter in pts who develop emboli despite adequate anticoagulation. If obvious
remedial cause, 6W of heparin is enough otherwise continue for at least 3-6M, longer if malignancy etc. Is there an
underlining cause e.g. malignancy, thrombolytic tendency? Start treatment ASAP when signs are good because most deaths
occur within an hour.
Management acute: O2 100%. Morphine IV with antiemetic if pt is in pain/very distressed. If critically ill with massive PE
consider immediate thrombolysis (50mg bolus of alteplase) or surgery. IV access & start heparin either low molecular
weight e.g. tinzapurin or unfractionated heparin IV bolus. If systolic 90> start warfarin PO. If systolic <90 start rapid colloid
infusion. If BP still ↓ after colloid, dobutamine IV aim for systolic 90>. If BP still low consider noradrenaline. If systolic <90,
clinically definite PE and no CI, consider thrombolysis.
Pleural effusion
 Ple ura l ef fus ion

Build up of fluid in the pleural cavity.

Causes: Pneumonia, TB, cancers. Some arthritic conditions. Heart failure causes back
pressure in the veins that take back blood to heart-some fluid may sweep out. Swelling of
legs is typical of heart failure but a pleural effusion can develop. Low level of protein in blood
tends to allow fluid to sweep out of blood vessels e.g. in liver cirrhosis, nephrotic syndrome.
Symptoms: Often painless but may feel chest pain. Breathlessness. Cough, fever.
Tests: CXR to confirm effusion. Also blood/lung/biopsy tests to check underlining cause of
pleural effusion.
Treatment: treatment of underlining cause is first carried out so effusion may go away.
Treatment of effusion only needed when it causes symptoms such as breathlessness-Pleural
fluid aspiration is used. Pleurodesis: a sclerosant such as tetracycline is injected into pleural
space to trigger and inflammation which causes pleura to stick together- commonly used in
recurrent effusions. Leaving a permanent drain in place. An operation to insert a
pleuroperitonal shunt (internal drain). Pleurectomy-used with pts with effusions due to
cancer as last resort.
Acute resp distress syndrome
 Acute Respiratory distress syndrome

Direct lung injury, secondary to severe systemic illness. Lung damage & release of inflammatory mediators cause increased
capillary permeability and non-cardiogenic pulmonary edema, often accompanied by multi-organ failure.
Causes: Pulmonary: gastric aspiration, inhalation injury, vasculitis, contusion. Other: shock, septicaemia, haemorrhage, multiple
transfusions, DIC, pancreatitis, acute liver failure, trauma, head injury, malaria, fat embolism, burns, obstetric events e.g.
eclampsia, drugs/toxins (aspirin/heroin).
Clinical features: Cyanosis, tachypnoea, tachycardia, peripheral vasodilation, bilateral fine inspiratory crackles.
Investigations: FBC, U&E, LFT, amylase, clotting, CRP, blood cultures, ABG. CXR shows bilateral pulmonary infiltrates. Pulmonary
artery catheter to measure pulmonary capillary wedge pressure (pcwp)
Diagnostic criteria: One consensus requires these 4 to exist: 1)acute onset 2)CXR: bilateral infiltrates 3)Pulmonary capillary wedge
<19/lack of clinical congestive heart failure 4) Refractory hypoxaemia with PaO2: Fi02<200 for ARDS. Others include total thoracic
compliance <30mL/cm h2O
Management: Admit to ITU; give supportive therapy; treat underlying cause. Respiratory support in early ARDS, continuous
positive airway pressure (CPAP) with 40-60% O2 may be adequate to maintain oxygenation, but most pts need mechanical
ventilation. Indications for ventilation: PaO2: <8.3kPa despite 60% O2;PaCO2: >6kPa. The large tidal volumes produced by
conventional ventilation plus reduced lung compliance in ARDS may lead to high peak airway pressures +/- pneumothorax. Low-
tidal volume, pressure-limited approach, with either low/moderate high positive end-expiratory pressure improves outcome.
Circulatory support: Invasive haemodynamic monitoring with an arterial line and swan-Ganz catheter aids the diagnosis and may
be helpful in monitoring pcwp and cardiac output- conservative fluid management improves outcome. Maintain cardiac output
and O2 delivery with inotropes e.g. dobutamine IVI, vasodilators & blood transfusion. Consider treating pulmonary
hypertension with low-dose NO-a pulmonary vasodilator. Hemofiltration may be needed in renal failure & to achieve a negative
fluid balance. Sepsis: ID and treat organisms accordingly. Other: nutritional support: entral is best with high fat antioxidant
formulations.
Prognosis: Overall mortality 50-75%
Infant resp distress syndrome
 Infant respiratory distress syndrome (IRDS)

Occurs due to the inadequate production of surfactant (which lowers surface tension) in the lungs- normally produced by type2 pneumocytes. This
causes air sacs to collapse on expiration & greatly increases energy required for breathing. Development of interstitial edema makes lungs less
compliant- leading to hypoxia and retention of CO2.
Risk factors: premature, male infants, C-section, hypothermia, perinatal asphyxia, maternal Diabetes, multiple pregnancy, family history. Secondary
IRDS: Intrapartum asphyxia, pulmonary infection, meconium aspiration pneumonia, O2 toxicity along with volume/pressure trauma to lungs,
congenital diaphragmatic hernia & pulmonary hypoplasia.
Presentation: usually preterm delivery, presents soon after birth with respiratory distress: tachypnoea, expiratory grunting, subcostal/intercostal
retractions, diminished breath sounds, cyanosis, nasal flaring. May rapidly progress to fatigue, apnoea, hypoxia.
Differentials: Pulmonary air leaks e.g. pneumothorax. In preemies, this may occur from excessive positive pressure ventilation/spontaneous. Infection,
pneumonia, transient tachypnoea(usually after C-section), congenital anomalies of lungs, congenital heart anomalies, primary persistent pulmonary
hypertension, metabolic problems e.g. hypoglycaemia, haematological problems e.g. anaemia.
Investigations: ABG(for respiratory/metabolic acidosis/hypoxia), Pulse oximeter (maintain O2 at 85-93%), CXR. Monitor FBC, electrolytes, glucose,
renal and liver function. Echocardiogram: diagnosing patent ductus arteriosus (PDA) determine direction/degree of shunting + confirm diagnosis of
pulmonary hypertension Exclude structural heart disease. Culture to rule out sepsis.
Management: Surfactant replacement therapy is given via an endotracheal tube- been shown to improve clinical outcome, ↓risk of pneumothorax
and pulmonary interstitial emphysema and also neonatal mortality. However, it ↑risk of developing PDA & pulmonary haemorrhage. O2 to maintain
O2 saturation between 85-93%. Continuous positive airway pressure (CPAP) keeps alveoli open at end of expiration- administered via endotracheal
tube, nasal prongs, nasalpharyngeal tubes. Assisted ventilation at fast rates improves outcome more than lower rates. Supportive: gentle & minimal
handling, temperature regulation, fluids/metabolism & nutrition- closely monitor+maintain blood glucose, electrolytes, acid balance, calcium,
phosphorus, renal function & hydration. Once infant stable, IV nutrition with amino acids+lipids. Once respiratory status is stable, initiate small-
volume feeds (preferably breast milk). Circulation & anaemia= monitor heart rate, bp, peripheral perfusion. Blood/volume expanders may be required.
Start antibiotics on all infants presenting with IRDS, stop slowly if blood cultures negative. Support family.
Complications: procedure related e.g. infection. Alveolar rupture e.g. pneumothorax. Intracranial haemorrhage. PDA. Persistent pulmonary
hypertension. Occurrence of pulmonary haemorrhage. HAI. Necrotising enterocolitis. Apnoea. Chronic lung disease. Neurological/hearing impairment.
Retinopathy.
Prevention: antenatal steroids, delay preemie birth, good control of maternal diabetes, avoid hypothermia in neonate.
TB
 tuberculosis

Kills 2m/yr. Most likely cause of death in HIV. If HIV+ risk is ↑if: CD4 ↓; ESR ↑; many coinfections; poor nutrition; high viraemia.
Signs & symptoms: Pulmonary TB: Silent/cough, sputum, malaise, weight loss, night sweats, pleurisy, haemoptysis (possibly
massive), pleural effusion/superimposed pulmonary infection, aspergilloma/mycetoma may form in cavities. Miliary TB: Occurs
following haematogenous dissemination. Signs may be non-specific. CXR shows characteristic reticulonodular shadowing. Look
for retinal TB. Biopsy: lungs/liver/lymph nodes/ marrow may yield AFB/granulomata. Genitourinary TB: may cause frequency,
dysuria, loin/back pain, haematuria, sterile pyuria. Renal TB may spread to bladder/seminal vesicles/epididymis/fallopian tubes.
Bone TB: vertebral collapse & Potts vertebra. Skin TB (lupus vulgaris): jelly-like nodules e.g. on face/neck. Peritoneal TB: Causes
abdominal pain/GI upset- look for AFB in ascites, laparotomy may be needed. Acute pericarditis: primary exudative allergic
lesion. Chronic pericardial effusion & constrictive pericarditis: Fibrosis/calcification may be prominent with spread to
myocardium (giving steroids in these pts for 11w alongside anti-TB drugs reduces need for pericardiectomy)
Diagnosis: Latent TB: Consider a mantoux test/interferon-gamma testing. Active TB: If CXR suggests TB, take sputum samples and
send for MC+S for AFB (acid-fast bacilli)- use induction of sputum/bronchoscopy & lavage if pt cannot produce sputum. Active
non-respiratory TB: Try hard to get relevant clinical samples: sputum, pleura & pleural fluid, urine, pus, ascites, peritoneum, bone
marrow or CSF. Send surgical samples for culture. Microbiology staff should routinely perform TB culture on above samples. Pts
with non-respiratory TB to have CXR to exclude coexisting respiratory TB. AFB resist acid-alcohol decolourisation under Ziehl-
Neeslen staining. PCR allows rapid ID of rifampicin resistance. Histology: The hallmark is the presence of caseating granulomata.
CXR signs: consolidation, cavitation, fibrosis, calcification. Immunological evidence of TB may be helpful: Tuberculin skin test: TB
antigen injected intradermally & cell-mediated response is recorded at 48-72h, +ve indicates immunity/previous exposure, strong
+ve indicates active infection, false negative occurs in immunosuppression. Quantiferon TB Gold and TB spots test: measure
delayed hypersensitivity reaction developed after contact with M. tuberculosis; use specific complex M. tuberculosis antigens &
are better than older mantoux tests.
 Tuberculosis continued…

Treatment of pulmonary TB: If histological/clinical picture are consistent with TB, start
treatment even if results are not out/negative. Before treatment: stress importance of
compliance. Check FBC, liver & renal function. Test colour vision & acuity before &
during treatment as ethambutol may cause ocular toxicity (reversible). Initial phase: 1)
Rifampicin PO 2) Isoniazid PO + pyridoxine (if diabetic/malnourished/renal
failure/alcoholic) 3) Pyrazinamide PO 4) Ethambutol PO /streptomycin. (Continuation
phase: (16w 2drugs) rifampicin & isoniazid at same doses. Give pyridoxine throughout
treatment. Steroid indicates in meningeal & pericardial disease.
Main SE: Rifampicin: Hepatitis (stop if bilirubin rises), orange discoloration of
urine/tears, inactivation of the pill, flu-like syndrome with intermittent use. Isonazaid:
Hepatitis, neuropathy, pyridoxine deficit, agranulocytosis. Ethambutol: Optic neuritis
(colour vision first to deteriorate). Pyrazinamide: Hepatitis, arthralgia (ci: acute
gout/porphyria).
Anti TB drug use in liver/renal failure: Monitor U&E + LFT before/after starting. In liver
failure get expert help. If creatine clearance=: Rifampicin: ↓dose by 50%. Ethambutol:
monitor u&e ; avoid if possible. No dose change for ethionamide/isoniazid.
Pulmonary oedema
 Acute Pulmonary edema
Causes: Cardiogenic pulmonary edema: caused by elevated pulmonary capillary pressure from left-sided heart failure. – Acute mi,
complications of coronary syndrome, valvular, hypertension, acute PE, acute myocarditis, aortic dissection, drugs, surgery etc. Non-
cardiogenic pulmonary edema: usually minimal elevation of capillary pressure, may be caused by altered-alveolar capillary membrane e.g.
ARDS. Uncommon in diminished plasma oncotic pressure & protein loosing enteropathy. Narcotic overdose, high altitude etc. Renal: acute
kidney/chronic renal failure, renal artery stenosis. Iatrogenic fluid overload, high-output heart failure e.g. septicaemia. Acute pulmonary
capillary permeability: ARDS, radiation, high altitude etc.
Signs: Usually severe breathless, nauseated & anxious. Initially may have dry/productive cough (sometimes frothy/pink). Pts may develop
paroxysmal nocturnal dyspnoea/orthopnea. Respiratory distress: pale/sweaty/tachypnoeic/tachycardic. May be cyanosed, congested veins &
raised JVP. basal./widespread fine crackles. O2 sat <90%. Assess for gallop (3rd heart sound), murmurs suggestive of valve problem.
Hypotension= systolic <90, low cardiac output: cardiogenic shock. In hypertensive heart failure: high bp/tachycardia/vascoconstriction
presents with signs of pulmonary edema without extensive systemic congestion. In right heart failure presenting with acute pulmonary
edema, hepatomegaly & peripheral edema are usual.
History: check for past history of relevant conditions: ischaemic/valvular heart disease, diabetes. Review current medication. Smoking &
alcohol.
Investigations: Blood tests: Renal function, electrolytes, glucose, cardiac enzymes, LFT’s. ABG & pH. Brain natriuretic peptides- helpful in
distinguishing acute pulmonary edema from other causes of dyspnoea. ECG: look for arrhythmia, MI, other cardiac diseases e.g. left
ventricular hypertrophy. CXR: To exclude other causes of breathlessness & confirm diagnosis. Transotheric Echocardiogram: to check for
weakness/thickness/failure to relax/leaky/valve problems. Urinary catheter: enables accurate measurement of urinary output, assess dirutic
response/fluid balance. More invasive procedures requires for intensive support.
(Pre hospital) Management: Resus if necessary, give 100% O2, If COPD, monitor ABG to avoid hypercapinia, aim for 90%> O2 sat in COPD and
95%> in non COPD. Insert IV canulla, give: Nitrates as first line vasodilators if BP 90> systolic, if no serious obstructive valvular disease, give
sublingual e.g. 2 puffs of glyceryl trinitrate. Furosemide IV (slowly), produces transient venodilation & subsequent diuresis (effect greatly
reduced in hypotension & when pt on oral diuretics for long time). Opiates: Diamorphine IV slowly used to relieve anxiety/pain/distress- not
to be given if pt has decompensated heart failure.
 Acute pulmonary edema

Initial Management (without shock): IV loop diuretic recommended to improve breathlessness & relieve congestion. Symptoms, urine output, renal function
& electrolytes should be monitored regularly during use of IV diuretic. High-flow O2 if O2 sat <90% or PaO2 <8kPa- not to be used routinely In non-
hypoxaemic pts- causes vasoconstriction & reduction in cardiac output. Thrombo-embolism prophylaxis e.g. low weight heparin if no contradictions to
reduce risk of DVT & pulmonary embolism. Opiates: e.g. morphine may reduce anxiety however it depresses respiratory drive potentially increasing need for
invasive ventilation- should not be routinely used as it increased mortality + in decompensated heart failure. Vasodilators: IV nitrates if systolic 110> & who
don’t have aortic/mitral stenosis- reduces capillary wedge pressure, also may relive dyspnoea & congestion, symptoms and BP to be monitored regularly.
Inotropic agents: NOT recommended unless in shock/hypotensive/hypoperfused-causes tachycardia & arrhythmias. Phosphodiesterase inhibitors preferred
for those on B-blocker therapy.
Pts with hypotension/hypoperfusion/shock: Electrical cardioversion is recommended if an atrial/ventricular arrhythmia is thought to be contributing to
haemdynamic compromise. IV inotrope e.g. dubutamine should be considered with hypotensive (<85systolic) pts= monitor ECG as inotropes cause
arrhythmias & myocardial ischemia. Short-term mechanical circulatory support for severely hyperperfused pts despite inotropic therapy with potentially
reversible cause e.g. viral myocarditis, also consider for pts rapidly deteriorating before full diagnostic & clinical evaluation is made. Vasopressor e.g.
dopamine may be considered in pts despite inotropes still have cardiogenic shock- intra-arterial bp should be measured. IV levosimendan may be considered
to reverse effects of B-blockade (thought to contributing to hypoperfusion).
Monitor: systolic BP, heart rate & rhythm, saturation of peripheral O2, urine output-until pt is stabilised. Examine pt repeatedly inc checking for new heart
murmers (for valve defects) Renal function/electrolytes/serial ECG’s/cardiac enzymes. Intra-arterial line: only for pts with persistent heart failure or low
systolic BP despite treatment.
After stabalization: ACE-inhibitors as soon as BP/renal
permitting + B-Blockers as soon as BP/heart rate permitting. Mineralocorticoid receptor agonist (MRA) as soon as renal/potassium permitting- due to MRA
having little effect on BP, relatively hypotensive pts could be started. Digoxcin: may control atrial fibrillation/symptom benefit/reduce risk of hospital
admission.
Non-invasive ventilation: CPAP (continuous positive airway pressure) can improve O2 sat. Should be considered in dyspnoeic pts and resp rate of >20/min to
improve breathlessness & reduce hypercapnia and acidosis. Not generally to be used on hypotensive pts as it reduced BP.
Endotracheal intubation & invasive ventilation: primary indication is respiratory failure leading to hypoxaema, hypercapnia & acidosis. Others: physical
exhaustion/diminished consciousness/inability to maintain/protect airway.
Mechanical circulatory support: to support circulation during surgical correction/severe acute myocarditis.
Venovenous for those unresponsive to diuretics.
 Severe acute respiratory syndrome (SARS)

Causes: CoV virus- a corona virus.

Major features: persistent fever >38 degrees, chills, rigors, myalgia, dry cough,
headache, diarrhoea & dyspnoea- with abnormal CXR and ↓wcc.
Animal reservoir: most likely bats
Mode of transmission: droplet
Complications: Respiratory failure (the big complication)
Management (is supportive): >50% need supplemental O2- ~20% progress to
acute respiratory distress syndrome requiring invasive ventilation. Rapid
diagnosis, early isolation & good infection control measures are vital.
Communicate with consultants in infectious diseases.
pneumonia
 Pneumonia
An acute lower respiratory tract illness associated with fever, symptoms and signs in the chest, and abnormalities on the
CXR. Incidence: 5-11/1000 (↑ in young/elderly). Mortality: 10%=hospital 30%=ITU.
Community acquired pneumonia (CAP): may be primary or secondary to underlying disease. Streptococcus pneumonia is
most common cause followed by haemophilus influenza and Mycoplasma pnumoniae. Staphylococcus aureus, Legionella
species, Moraxella catarrhalis and Chlamydia account for most remainder. Gram negative bacilli, Coxiella burnetii and
anaerobes are rarer. Viruses account for 15%. Flu may be complicated by community-acquired MRSA pneumonia (CA-
MRSA).
Hospital acquired (nosocomial; 48h after hospital admission). Most commonly Gram negative enterbacteria/staph aureus.
Also pseudomonas, Klebsiella, Bacteroides, and Clostridia.
Aspiration: those with stroke, Myasthenia, bulbar palsies, ↓consciousness(e.g. post-ictal or drunk), oesphgeal disease
(achalasia, reflux), or with poor dental hygiene, risk aspirating oropharyngeal anaerobes.
Immunocompromised patient: Strep. Pneumoniae, H.influenza, Staph.aureus, M.catarrhalis, M.pnumoniae, Gram –ve
bacilli & Pneumocytis jirovecia. Other fungi, viruses & mycobacteria.
Clinical features: symptoms: Fever, rigors, malaise, anorexia, dyspnoea, cough, purulent sputum, haemoptysis, and
pleuritic pain. Signs: Fever, cyanosis, confusion (may be only sign in elderly), tachypnoea, tachycardia, hypotension, signs
of consolidation (diminished expansion, dull percussion note, ↑tactile vocal fremitus/vocal resonance, bronchial
breathing), and a pleural rub.
Tests: aim to establish diagnosis, ID pathogen + assess severeity. CXR: lobor/multilobar infiltrates, cavitation/pleural
effusion. Assess oxygenation, O2 sat (ABG if SaO2 <92% or severe pneumonia). Blood tests: FBC, U&E, LFT, CRP, blood
cultures. Sputum for microscopy & culture. In severe cases, check for Legionella (sputum culture, urine antigen), atypical
organism/viral serology & check for pneumoccal antigen in urine. Pleural fluid may be aspirated for culture. Consider
bronchoscopy and bronchoalveolar lavage if pt is immunocomp or on ITU.
 Pneumonia carried on…
Severity: ‘CURB’=Confusion (abbreviated mental test <8), Urea= >7mmol/L;
Respiratory rate= 30>/min BP= <90 systolic and/or 60 diastolic; age 65. 0-1 feature
present: home treatment possible; 2 hospital therapy; >3 indicates severe pneumonia
(consider ITU). Other features increasing risk of death: co-existing disease;
bilateral/multilobar involvement; PaO2 <8kPa/SaO2 <92%.
Management: Antibiotics- Mild (Strep pneumonia/Haemophilus influenza): oral
amoxicillin. Moderate (Strep pneumonia/Haemophilus influenza/ Mycoplasma
pneumonia): Oral amoxiccilin + clarithromycin. If IV: amoxicillin + clarithromycin.
Severe (as above: Co-amoxiclav IV AND clarithromycin IV. Add flucloxaccilin if staph
suspected; vancomycin if MRSA suspected= teicoplanin. Treat for 10d (12-21d if staph
or gram –ve bacteria suspected. Atypical(Legionella pneumophilia/Chlamdyophilia
species/Pneumocystis jiroveci): Consider adding rifampicin; Tetracycline and high dose
co-trmoxazole respectively. Hospital acquired (gram neg bacilli, Pseudomonas,
Anaerobes): Aminoglycoside IV + antipseudomonal penicillin IV and cephalosporin
respectively. Aspiration(Strep pneumonia/Anaerobes): Cefuroxime IV + metronidazole
IV. Neutropenic pts (gram + cocci/gram ve- bacilli): Aminglycoside IV +
antipseudomonal penicillin IV. Fungi= Consider antifungals after 48h.
 Q-fever
Caused by Coxiella burnetti (100/yr in UK). So named because it was first labelled ‘query’ fever in
workers in an Australian abattoir.
Epidemiology: Occurs worldwide, usually rural, with resevoirs in cattle & sheep. Organism
resistant to drying & usually inhaled from infected dust. Can be contracted from unpasteurized
milk, directly from carcasses in abattoirs, sometimes by droplet spread & rarely from tick bites.
Clinical features: suspect Q fever in anyone with PUO/atypical pneumonia. Fever, myalgia,
sweats, headache, cough & hepatitis may be present. If disease becomes chronic, suspect
endocarditis (typically ‘culture negative’). Aortic valve usually affected- clinical signs may be
absent. Causes miscarriages & CNS infection.
Tests: CXR may show consolidation= multilobar or slowly resolving. Liver function tests may be
hepatitic & biopsy may show granulomata. Diagnosis is serological: indirect immunofluroesence
essay is most dependable & widely used method. Increased IgG & IgA antibodies to phase I are
often indicative of Q-fever endocarditis. Phase I antigens suggest chronic infection; phase II
antigens suggest acute infection. PCR may be used on tissue samples. CSF may be needed.
Treatment: get expect microbiological help. Acute: Doxycycline PO. Minocycline,
clarithromycin, ciprofloxacin (in pregnancy) & co-trimoxazole are used. Q fever endocarditis:
treatment is difficult e.g. doxycycline + hydroxy-chloroquine e.g. PO +/- valve replacement.
 Klebsiella (pneumonia)
Klebsiella pneumonia is rare. Occurs in elderly, diabetics & alcoholics. Causes
cavitating pneumonia, particularly of the upper lobes, often drug resistant.
Treatment: Cefotaxime/imipenem.
Chlamidophilia psittacosis pneumonia
Chlamydophilia Psittacosis (pneumonia)
Causes: psittacosis, an ornithosis acquired from infected birds (typically
parrots).
Symptoms: headache, fever, dry cough, lethargy, arthralgia, anorexia &
D&V. Extra-pulmonary features: meningo-encephalitis, infective
endocarditis, heptatitis, nephritis, hepatitis, rash, splenomegaly.
Tests: CXR shows patchy consolidation.
Diagnosis: chlamdyophilia serology.
Treatment: tetracycline/clarithromycin.
Legionella pneumonia
 Legionella pneumonia

Colonizes water tanks kept at <60 degrees Celsius e.g. hotel air
conditioning and hot water systems causing outbreaks of legionnaires
disease.
Signs & symptoms: flu-like symptoms, fever, malaise, myalgia- precede
a dry cough and dyspnoea. Extra-pulmonary features include anorexia,
D&V, hepatitis, renal failure, confusion & coma.
Tests: CXR shows bi-basal consolidation. Blood tests may show
lymphopenia, hyponatraemia, and deranged LFT’s. urinalysis may show
haematuria.
Diagnosis: Legionella serology/urine antigen.
Treatment: clarithromycin +/- rifampicin PO.
Mortality: 10%
 Whooping cough (pertussis)

Humans are both natural host & reservoirs of infection. Caused by bordetella pertussis and B.
bronchiseptica produce milder infections. Highly contagiois & spread by droplets. In early stages its
indistinguishable from other types of URTI infections. Disease uncommon now.
Clinical features: incubation period: 7-10d. It’s a disease of childhood with 90% of cases in children
<5yrs although no age is exempt. During catarrhal stage patient is highly infectious and cultures from
respiratory secretions are + in over 90% of pts. Malaise, anorexia, mucoid rhinorrhoea (significant fluid
in nasal cavity) and conjunctivitis are present. The paroxysmal stage is so called because of the
characteristic paroxysms of coughing, begins about 1week later- paroxysms with the classic inspiratory
whoop is seen only in younger individuals in whom lumen of respiratory tract is compromised by mucus
secretion & mucosal edema. Conjunctivial suffusion and petechiae & ulceration of the frenulum of
tongue are usual. Lymphocytosis due to elaboration of lymphocyte-promoting facto by B. pertussis is
characteristic- this stage lasts 2wks & may be associated with several complications, including
pneumonia, atelectasis, rectal prolapse & inguinal hernia. Cerebral anoxia may occur, especially in
younger children, resting in convulsions. Bronchiectasis is a rare sequel.
Diagnosis: clinical characteristics and history of contact with an infected individual. Confirmed by
culturing the organism from naso-pharyngeal swab. PCR assays also available.
Treatment: if disease detected in catarrhal stage, macrolides will abort/decrease severity of infection
(although resistance has been reported). Azithromycin frequently used. In paroxysmal stage, antibiotics
have little to play in altering course of illness.
asbestosis
 Asbestosis

Causes: inhalation of asbestos fibers. White asbestos is least fibrogenic and blue
asbestos is most fibrogenic, brown is intermediate fibrogenic. Asbestos was
commonly used for building trade- fire proofing, pipe lagging, electrical wire
insulation & roofing felt. Degree of asbestos exposure related to degree of
pulmonary fibrosis.

Clinical features: Similar to other fibrotic lung diseases with progressive

dyspnoea, clubbing & fine-end respiratory crackles. Also causes pleural plaques,
↑risk of bronchial adenocarcinoma & mesothelioma.

Management: symptomatic. Pts often eligible for compensation via UK

Industrial Injuries Act. No treatment known to alter progress of disease but
corticosteroids often provided.
 Laryngitis
Inflammation of the larynx usually caused by a viral infection.
Other causes: rare infections, allergies, voice overuse, acid reflux, smoking,
irritants/chemicals inhaled.
Signs & symptoms: soreness in front of neck, hoarseness-leading to whispering only,
mild fever, cough, tonsillitis, flu-like illness, sore throat, headache, feeling tired, swollen
neck glands, runny nose, pain on swallowing, general aches & pains. Rarely the
inflammation will cause the airways to narrow leading to dyspnoea. All symptoms are
temporary- they get worse over 2-3days but subside within a week- hoarseness of
voice may continue for another week or so.
Treatments: None as laryngitis usually gets better within a few days. Drinking plenty of
fluids even if it hurts as even mild dehydration leads to headaches & tiredness getting
worse. Paracetamol/Ibuprofen to help ease pain/headache/fever.
Gargles/lozenges/sprays-little help. Breathing humidified air helps by soothing airways
& help to clear secretions. Resting the voice- not shouting/singing/talking for long
periods- you should rather talk in sighing soft speech rather than whisper as a whisper
makes larynx work harder. If singing career is affected contact speech therapist.
Bronchogenic CA
 Bronchogenic carcinoma

Accounts for 19% of all cancers & 27% of cancer deaths. Incidence increasing in women.
Risk factors: smoking (major), asbestos, chromium, arsenic, iron oxides & radiation (radon gas).
Histology: squamous (35%), adenocarcinoma (27%), small cell (20%), large cell (10%), alveolar cell carcinoma rare (<1%). Clinically most important
division is between small cell and non-small cell.
Symptoms: cough (80%), haemoptysis (70%), dyspnoea (60%), chest pain (40%), recurrent/slowly resolving pneumonia, anorexia, weight loss.
Signs: Cachexia, anaemia, clubbing, wrist pain, supraclavicular/axillary nodes. Chest signs: none/consolidation/collapse/pleural effusion.
Metastases: bone tenderness/hepatomegaly/confusion/fits/focal CNS signs: cerebellar syndrome/proximal myopathy/peripheral neuropathy.
Complications: Local: recurrent laryngeal nerve palsy; phrenic nerve palsy; SVC obstruction; horners syndrome, rib erosion, pericarditis, AF.
Metastatic: brain/bone/, PTH ↑Ca2+ , liver/ adrenals. Endocrine: ectopic hormone secretion e.g. SIADH, ↑ADH ↓Na+, ACTH (cushings) by small
cell tumours, PTH (↑Ca2+ ) by squamous cell tumours. Non-metastatic neurological: confusion, fits, cerebellar syndrome, proximal myopathy,
neuropathy, polymyositis, Lambert-Eaton syndrome. Other: clubbing, HPOA, dermatomyositis; acanthosis nigricans; thrombophlebitis migrans.
Tests: Cytology: sputum & pleural fluid (send at least 20mL). CXR: peripheral nodule, hilar enlargement, consolidation, lung collapse, pleural
effusion, bony secondaries. Peripheral lesions & superficial lymph nodes may be amenable to percutaneous fine needle aspiration/biopsy.
Bronchoscopy: to give histology & assess operability. CT to stage tumour. PET/CT scan to help in staging. Radionuclide bone scan: if suspected
metastases. Lung function test: to help assess suitability for lobectomy.
Treatment: Non-small cell tumours: excision is the treatment of choice for peripheral tumours with no metastatic spread: stage 1 or 2 (25%).
Curative radiotherapy is an alternative if respiratory reserve poor. Chemotherapy +/- radiotherapy for more advanced disease. Regimens may be
platinum-based e.g. with monoclonal antibodies targeting the epidermal growth factor receptor. Get specialist help. Small cell tumours are nearly
always disseminated at presentation. May respond to chemotherapy but invariably relapse. Palliation: Radiotherapy is used for bronchial/SVC
obstruction, haemoptysis, bone pain & cerebral metastases. SVC stent + radiotherapy & dexamethasone for SVC obstruction. Endobronchial
therapy: tracheal stunting/cryotherapy/laser/brachytherapy. Pleural drainage/pleurodesis for symptomatic pleural effusions. Drugs:
analgesia/steroids/antiemetics/cough linctus/bronchodilators/antidepressants.
Prognosis: Non-small cell: 50% 2yr survival without spread; 10% with spread. Small cell: median survival- 3 months if untreated; 1-1.5yrs if treated.
Prevention: quit smoking, prevent occupational exposure to carcinogens.
Mesothelioma
Tumour of the mesothelial cells that usually occurs in the pleura & rarely in the peritoneum or other organs. It is
associated with occupational exposure to asbestos but relationship is complex. 90% report previous exposure to
asbestos but only 20% have pulmonary asbestosis. Latent period between exposure & development of tumour may
be up to 45yrs.

Clinical features: chest pain, dyspnoea, weight loss, finger clubbing, recurrent pleural effusions. Signs of metastases:
lymphadenopathy, hepatomegaly, bone pain/tenderness, abdominal pain/obstruction (peritoneal malignant
mesothelioma)

Tests: CXR/CT: pleural thickening/effusion. Bloody pleural fluid.

Diagnosis: made on histology following pleural biopsy- Abrams needle, thoracoscopy. Often the diagnosis is only
made post-mortem.

Management: Pemetrexed + cisplatin chemotherapy can improve survival. Surgery is hard to evaluate.
Radiotherapy is controversial.

Prognosis: poor especially with pemetrexed= <2yrs.

 Cancer of larynx

2nd most common form of head & neck cancer. 14th most common cancer in men but much rarer in women. Peak incidence between 50-60yrs.
Risk factors: heavy smoking/alcohol, HPV virus which ↑risk of oral/pharyngeal/laryngeal cancer. Occupational exposure to asbestos, formaldehyde, nickel,
isopropyl alcohol & sulphuric acid mist have been linked to laryngeal cancer. Exposure to diesel fumes ↑risk.
Presentation: chronic hoarseness (most common early symptom), dysphagia, lump in the neck, sore throat, earache, persistent cough. Breathlessness,
aspiration, haemoptysis, fatigue & weakness, weight loss.
Examination: Head & neck exam includes: inspection/palpation of oral cavity & oropharynx to rule out second primary tumours or other lesions, as well as
evaluation of dentition. Palpation of neck looking for enlarged lymph nodes is essential. Thorough examination of cranial nerves to be included.
Differentials: sore throat, earache/cough.
Investigations: Urgent X-Ray for pts with persistent hoarseness lasting for more than 3weeks, particularly smokers aged 50> & heavy drinkers- if abnormality
found refer urgently to team specialising in management of lung cancer- if normal then refer to head and neck cancer specialists. Flexible laryngoscopy- best
way to inspect larynx- good for staging tumour & locating. Fine needle aspiration of neck mass. CT/MRI/PET scans & pulmonary function tests.
Staging: The 'tumour, nodes, metastases' (TNM) staging system is used for staging head and neck cancers. T is the extent of the primary tumour; N is the
involvement of regional lymph nodes; M is the presence of metastases. The depth of infiltration is predictive of prognosis. Higher the numbers, the more its
spread etc.
Management: Transolar laser microsurgery: for early-intermediate glottic & supraglottic cancer. Open partial laryngectomy: for more advanced tumours.
Total laryngectomy: considered in cases of bulky/advanced disease. Early glottic cancer: treat with external beam radiotherapy/conservation surgery. Early
supraglottic cancer: External beam radiotherapy (should include prophylaxis of the lymph nodes bilaterally of neck)/conservational surgery. Endoscopic laser
excision/superglotic larynxgectomy with selective dissection of lymph nodes of neck- bilateral if tumour not well localised to 1 side. Locally advanced
resectable cancer: total laryngecetomy with/without post-operative radiotherapy. Treatment for organ preservation/non resectable disease should be
concurrent chemoradiation with single-agent cisplatin- if pt medicaly unsuitable for chemo, concurrent administration of cetuximab with radiotherapy should
be considered. Radiotherapy should only be used as sole treatment if comorbidity prevents effects of concurrent chemo/cetuximab/surgery. In pts with T4
(metastatic) tumours treatment is total laryngectomy with post-operative radiotherapy. In pts with N0 (no metastases) treatment should be surgery &
external beam therapy- if tumour not localised to one side then both sides of neck should be treated. Pts with clinically node positive neck- treat with radial
neck dissection, post-op chemo/radio when indicated.
Complications: Dyspahia/malnutrition, loss of voice trachea-innominate artery fistula, loss of taste, surgery: post-op pharyngcutaneous fistula, chemo:
immunsupression, Radiotherapy: local fibrosis/scarring, oesophageal stricture/ dry mouth.
Prevention: smoking cessation, moderate alcohol intake etc
 Cor pulmonale

Enlarged arteries and ventricles

 Cor pulmonale

Cor pulmonale is right heart failure caused by chronic pulmonary arterial hypertension.
Causes: chronic lung disease, pulmonary vascular disorders, neuro-muscular & skeletal diseases.
Symptoms: dyspnoea, fatigue/syncope.
Signs: cyanosis, tachycardia, raised JVP with prominent a and v waves, RV heave, loud P2,
pansystolic murmur (tricuspid regurgitation), early diastolic graham steel murmur, hepatomegaly
and oedema.
Investigations: FBC: hb and haematocrit ↑(secondary polycythaemia). ABG: hypoxia
with/without hypercapnia. CXR: enlarged right atrium & ventricle, prominent pulmonary
arteries. ECG: P Pulmonale; right axis deviation; right ventricular hypertrophy/strain.
Management: treat underlying cause- e.g. COPD & pulmonary infections. Treat respiratory
failure- in acute situation give 24% O2 if PaO2 <8kPa. Monitor ABG & gradually ↑O2 conc. If
PaCO2 is stable. Pts with chronic hypoxia when clinically stable should be assessed for LTOT.
Treat cardiac failure with diuretics such as furosemide e.g. PO. Monitor U&E & give amiloride or
potassium supplements if necessary. Alternative: spironolactone. Consider venesection if
haematocrit >55%. Consider heart-lung transplantation in young pts.
Prognosis: poor. 50% die within 5yrs.
 CF

CXR shows bilateral pneumothorax and bilateral interstitial infiltration

(first one on left and also usually is hyper inflated but not shown here.
 Cystic fibrosis

One of the commonest life-threatening autosomal recessive conditions affecting Caucasians.

Caused by mutations in the CF transmembrane conductance regulator (CFTR) gene on
chromosome 7. the CL- channel defect leads to a combo of defective chloride secretion & ↑Na
absorption across airway epithelium. The changes in composition of airway surface liquid
predispose the lung to chronic pulmonary infections & bronchiectasis.
Clinical features: neonates: failure to thrive; meconium ileus; rectal prolapse. Children and
young adults: respiratory, cough, wheeze, recurrent infections, bronchiectasis, pneumothorax,
haemoptysis, respiratory failure, cor pulmonale. GI: pancreatic insufficiency (DM etc), distal
intestinal obstruction syndrome (meconium ileus equivalent); gallstones; cirrhosis. Other: male
infertility, osteoporosis, arthritis, vasculitis, nasal polyps, sinusitis, hypertrophic pulmonary
osteoarthropathy (HPOA). Signs: cyanosis, finger clubbing, bilateral coarse crackles.
Diagnosis: sweat test: sweat sodium and chloride >60mmol/L chloride usually>sodium.
Genetics: screening for known common CF mutations should be considered. Faecal elastase is a
simple and useful screening test for exocrine pancreatic dysfunction.
Tests: blood: FBC, U&E, clotting, vitamin A, D ,E levels, annual glucose tolerance test.
Bacteriology: cough swab, sputum culture. Radiology: CXR, hyperinflation, bronchiectasis.
Abdominal US: fatty liver, cirrhosis, chronic pancreatitis, spirometry: obstructive disease.
Aspergillus serology/skin test (20% develop ABPA). Biochem: faecal fat analysis.
 Cystic fibrosis (management) continued…

Management: best done by multidisplinary team e.g. physio, GP, physican etc.
Chest: physiotherapy regularly (postural drainage, active cycle breathing
techniques). Antibiotcs: given for acute infective exaerbations & prophylactically
(PO or nebulized). Mucolytics may be useful e.g. dornase alfa nebulized.
Bronchodilators.
GI: pancreatic enzyme replacement; fat soluble vitamin supplements (A, D, E
,K). Ursodeoxycholic acid for impaired liver function; cirrhosis may require liver
transplantation.
Other: treatment of CF-related diabetes; screening for & treatment of
osteoporosis; treatment of arthritis & vasculitis; fertility & genetic counselling.
Advanced lung disease: O2, diuretics (cor pulmonale), non-invasive ventilation,
lung/heart transplantation.
Prognosis: median survival now over 30yrs.
 Vitamin D deficiency
Vitamin D is a vitamin that is needed for good health. Unlike other vitamins, we do not need to get vitamin D from food. A main source of
vitamin D is made by our own bodies. It is made in the skin by the action of sunlight. This is a good thing because most foods contain no or
very little vitamin D naturally. Foods that contain vitamin D include:
Best sources of Vitamin D:
• Oily fish (such as sardines, pilchards, herring, trout, tuna, salmon and mackerel).
• Fortified foods (this means they have vitamin D added to them) such as margarine, some cereals, infant formula milk.
• The best dietary source of vitamin D is oily fish and cod liver oil. There is little or no vitamin D in UK milk and dairy products. Only infant
formula milk and margarine have statutory vitamin D supplementation in the UK. Egg yolk, liver, and wild mushrooms contain only small
quantities of vitamin D.
Causes: Lack of sun exposure or the darker the skin the less likely vitamin D will be synthesised. Also low milk intake (diet) Certain
medications.
Symptoms:
• General tiredness, vague aches and pains and a general sense of not being well are the common symptoms.
• Rickets (softening of bones)
• In more severe deficiency (known as osteomalacia), there may be more severe pain and also weakness. Muscle weakness may cause
difficulty in climbing stairs or getting up from the floor or a low chair, or can lead to the person walking with a waddling pattern.
• Bones can feel painful to moderate pressure (often more noticeable in the ribs or shin bones). Not uncommonly, people have a hairline
fracture in the bone which is causing tenderness and pain. Bone pain often also occurs in the lower back, hips, pelvis, thighs and feet.
How diagnosed: Simple blood test for vitamin D. also blood test for calcium & phosphate levels.
Treatment: Vitamin D supplements.
Vit A deficit
 Vitamin A deficiency
Vitamin A (retinol) is a fat-soluble vitamin, present in liver, milk and eggs.
Causes:
• This is caused by prolonged dietary deficiency, particularly where rice is the staple food (doesn't contain carotene).
• Vitamin A deficiency occurs with protein-energy malnutrition (marasmus or kwashiorkor) mainly because of dietary deficiency (but
vitamin A storage and transport are also impaired).
Symptoms:
• Changes in the eye e.g. itching, burning or inflammation. Xeropthalmia- e.g. cornea becomes wrinkled. final stage is
keratomalacia-softening and destruction of eyeball leading to blindness.
• Epithelial changes- e.g. sinus infection and of tracts
• Skin changes- e.g. dry and scaly skin
• Changes to respiratory tract e.g. dry, itchy throat
• Changes in reproductive tracts e.g. vaginitis
• Urolithiasis- condition where urinary calculi (stones) are present
• Changes in skeletal system e.g. distortions of brain & spinal cord
• Lowered resistance to infection
Investigations: FBC, serum levels, iron and zinc studies & renal function tests
Management: consumption of vitamin A rich foods: liver, beef, chicken, eggs, fortified milk, carrots, mangoes, sweet potatoes and
leafy green vegetables, egg and milk. Also oral Vitamin A supplements.
 Vitamin C deficiency

Vitamin C cannot be made by the human body and so is an essential component of the diet. It is needed for the health and
repair of various tissues in the body, including skin, bone, teeth and cartilage. Chronic (persistent) lack of vitamin C in the diet
can lead to a condition called scurvy. Symptoms of scurvy include easy bruising, spontaneous bleeding and joint and muscle
pains. Vitamin C deficiency can be treated with supplements of vitamin C and a diet rich in vitamin C. 
Symptoms:
• Tiredness and weakness, Muscle and joint pains , Easy bruising. Spots that look like tiny, red-blue bruises on the skin. Dry
skin. Splitting hair. Swelling and discoloration of the gums. Spontaneous bleeding from the gums. Nosebleeds. Poor healing
of wounds. Problems fighting infections. Bleeding into joints, causing severe joint pains. Changes in the bones. Tooth loss.
Weight loss.

Investigations: Blood test, xray.

Treatment: Vitamin C supplements, diet rich in vitamin C.

 Antibodies
• IgG= Most common antibody
• IgA= Sweat and milk
• IgM= First on the scene
• IgE= Allergy/parasite
• IgD= B-cell activation
 Cell counts- what they tell you
• WBC↓ = patient may be immunocompromised
• Neutrophil↑= Patient may have bacterial infection
• lymphocyte↑= Acute viral infection
• Eosinophil↑= Parasitic, allergies
• U&E normal= nothing such as hypo/hyper calcaemia
• RCC↑= polycythaemia
• Hamaeglobin↓= anaemia
• WCC↓= radiotherapy, chemotherapy, anaemia, TB etc
• WCC↑= Infection, malignancy
• Basophil↑= myeloproliferative disease
• Monocyte↑= chronic inflammation
• urea↑creatinine↑= consider kidney damage
• urea↑normal creatinine= unlikely renal cause
• Urea↑Haemoglobin↓= consider upper GI bleed
• Potassium derangement’s lethal, must be corrected ASAP
• Na derangement’s often presents with neurological symptoms
• GGT↑from liver enzymes= Alcohol liver damage
• ↓CRP= exclude acute infection
• ESR/Plasma viscosity↑= Chronic inflammatory conditions
 Placenta Previa
In some cases, the entire or part of the placenta may become implanted in inferior part of uterus, near or covering internal os
of cervix
• May lead to spontaneous abortion
• Dangerous to fetus- premature birth possible and intrauterine hypoxia due to maternal bleeding
• Maternal mortality increased due to haemorrhage & infection
Symptoms: sudden, painless bright red vaginal bleeding in 3 rd trimester.
Treatment: C section is preferred delivery
Ectopic pregnancy
Development of fetus/embryo outside uterine cavity
Cause’s:
• Usually occurs when movement of fertilised ovum through uterine tube is impaired by scarring due to
tubal infection, decreased movement of smooth muscles, uterine tube surgery or previous ectopic
• Smoking women 2x likely to have ectopic pregnancy due to paralysis of cilia from nicotine in lining of
uterine tube
Signs & symptoms: 1 or 2 missed periods, bleeding & acute abdominal/pelvic pain
Unless removed, embryo can rupture uterine tubes leading to death of mother
Treatment: surgery or methotrexate- a cancer drug to stops cell dividing (of embryo)
Anencephaly
• Anencephaly
• Neural tube defect- caused by arrest of normal development & closure of
neural tube
• Cranial bones fail to develop & certain parts of brain remain in contact
with amniotic fluid and degenerate
• Usually parts of brain controlling vital functions eg breathing & heart
circulation is affected
• Babies are usually still born or die few days after birth. Condition 2-4x
more common in female than male infants
• Folic acid supplements can prevent this (take when preggers)
Pregnancy induced hypertension
• An elevated bp associated with pregnancy
• Major cause- preeclampsia which is abnormal condition of pregnancy
characterised by sudden hypertension, large amounts of protein in urea &
generalised oedema
• Other signs & symptoms: generalised edema, blurred vision & headaches
• May result from autoimmune/allergic reaction to fetus
• Treatment: bed rest and drugs such as magnesium
• When condition is associated with convulsions & coma its termed
eclampsia
 
Pre-eclampsia

Symptoms and signs: hypertension/ proteinurea

Tests: urinalysis
Management: lebtalol- B-blocker.
PCOS

Symptoms & signs: hirsutism/ ACNE/ most common feature: sub-

fertility. infertility
Investigations: testosterone
Management:
Oral contraceptives – if don’t wana get pregnant
Clomifene- if wana get pregnant
Co-cypryndole- hirsutism
Dystocia (difficult birth)
• May result from either from an abnormal position of fetus or birth
canal of inadequate size to permit vaginal delivery
• Breech presentation= buttocks/lower limbs of fetus rather than head
enter birth canal first-most often occurring in premature births
• If fetal/mother is in distress preventing delivery, C section is used
Preemie baby
• A baby who weighs less than 5.5 stones- generally is termed premature
• Causes: poor prenatal care, drug abuse, history of previous premature
delivery, mothers age ↑ 35 and ↓ 16 increase chances of premature
delivery
• Body of premature is not fully developed to some sustain critical functions
• Major problem with infants born under 36W is resp distress syndrome
(RDS) due to insufficient surfactant
• RDS can be eased using artificial surfactant & ventilator to deliver O2 until
lungs operate on their own
Endometrial cancer
 Endometrial cancer

Pathogenesis: endometroid represents 75-80% & includes ciliated adenocarcinoma, secretory adenocarcinoma, papillary/villoglandular
& adenocarcinoma with squamous differentiation. Uterine papillary serous <10%, mucinous 1%, clear cell 4%, squamous cell <1%,
mixed= 10%. May be undifferentiated.
Epidemiology: 90% of women with endometrial cancer over 50yrs. Affects 1/100, usually in mid to late 50s but it can be into later life.
Most common in western societies, becoming more common in Asia.
Risk factors: prolonged periods of unopposed oestrogen (not modified by effects of progesterone) are main risk factor. May occur as a
result of medication or anovulatory cycles where corpus luteum fails to mature & secrete progesterone. Histoligical diagnosis difficult in
that gross endometrial hyperplasia can look like well-differentiated carcinoma. Being nulliparous (never given birth to live/viable fetus)
↑risk 2-3 fold- may be by choice or as a result of infertility with anovulatory cycles. Menopause past age 52. obesity ↑oestrogen levels:
DM also ↑risk but may simply be linked to obesity. PCOS & insulin resistance also associated with obesity. ↑obesity ↑risk. Women who
have hereditary nonpolypsos colon cancer have 22-50% chance of developing endometrial carcinoma. Exogenous hormones can have
marked different effects. The anti-oestrogenic or pro-oestrogenic effects of a synthetic hormone varies between tissues such as
tamoxifen. Tibolone- doubles risk. Combined oral contraceptives ↓risk later in life- prolonged use benefits even after 15yrs of stopping
pills. HRT with oestrogen ↑risk but HRT with progestorens counteracts this.
History: post-menopausal bleeding- may not be case so must exclude. Usually presents around/before menopause in 10-25% cases.
Exam: even with advanced disease there is unlikely to be any physical abnormalities.
Investigations: smear test. Transvaginal US, mean endometrial thickness is much thinner in premenopausal women than post. Thickening
may indicate presence of cancer, the thicker the endometrium ↑chances of cancer being present (more than 5mm). Hyesterscopy and
biopsy should be performed if ↑clinical suspicion.
Staging: total abdominal hysterectomy with bilateral salpingoophrectomy is required both as a primary treatment and for the purpose of
staging. Stage 1 endometrial cancer is carcinoma confined to corpus uteri: IA) confined to endometrium with no, or less than half
myometrium invaded IB) invasion equal to, or more than half of myometrium. Stage 2 involves corpus and there is invasion into cervical
stroma, but has no extended outside uterus. Stage 3 has local/regional spread beyond uterus: A) invasion of serosa/ve+ peritoneal
cytology & possibly more than one of these. B) vaginal/para-metrial metastases C) metastases to pelvic (iiic1) or para-aortic (iiic2) lymph
nodes, or both. Stage 4 is involvement of bladder/bowel mucosa/distant metastasis: A) involvement of bladder/bowel mucosa B) distant
metastases including nodes in the abdomen/inguinal region.
 Endometrial cancer continued…

Management: stage 1 requires total abdominal hysterectomy with bilateral salpingo-

oophorectomy. Stage 2 requires radical hysterectomy with systemic pelvic node
clearance. Para-aortic lymphadenectomy may also be considered. Stage 3&4:
requires maximal de-bulking surgery. Also combo of surgery & chemo &
radiotherapy. Open surgery/laparoscopic methods- latter has better post-op recovery.
If surgery CI, then external beam radiotherapy & intercavity radiotherapy may be
used. Radiotherapy may result in recurrence- radical radiotherapy is effective for local
recurrence in over half of cases. Doxurubin gives good use but often temp response.
Paclitaxel & carboplatin also used. Tamoxifen may have useful adjuvant effect.
Prognosis: 20yr survival rate for all forms is 80%. Clear cell= 62%, papillary
carcinoma=53%. Depends on type & stage of tumour.
Stage 1: 92% 5yr survival
Stage 2: 75% 5yr survival
Stage3: 50% 5yr survival
Stage 4: 20% 5yr survival
 Prematu re ovarian failure

When eggs stop working before age of 40, can develop from teen years or as early as birth.
Likely to have no/irregular periods, infertility problems & menopause-like symptoms. Difficult
but not impossible for pts to get pregnant. Sometimes the condition is temp and other times
its permanent.
Causes: idiopathic, genetic, immune system, hysterectomy, pelvic surgery,
radiation/chemotherapy.
Symptoms: similar to menopause, so irregular or no periods. Some or all symptoms of
menopause: hot flashes, night sweats, irritability, vaginal dryness, low sex drive or trouble
sleeping.
Diagnosis: if periods are irregular/stop, then physical exam is carried out. History of general
health and symptoms of premature ovarian failure is taken. Pregnancy test. Blood test to find
out other causes of irregular periods. FSH levels are taken from blood test- if high then sign of
the condition. Oestrogen levels are taken from blood test- if low then sign of condition.
Management: HRT- with oestrogens and progestin's to relieve symptoms of oestrogen
deficiency and to maintain bone density. Androgens for women with persistent fatigue, low
libido, poor well-being despite treatment & when depression ruled out/adequtly treated.
PCOS

US shows cysts
 Polycystic ovarian syndrome

At least 12 cysts develop in ovaries/ ovaries make abnormally high amount of testosterone/ irregular or no
ovulation. Possible to have PCOS without typical symptoms.
Prevalence: common. About 1 in 10.
Causes: insulin resistance (which results in ↑levels of insulin in blood) causes high testosterone production-
causing excessive hair growth & thinning of scalp. ↑levels of insulin contributes to weight gain. ↑LH and
↑insulin results in ↑testosterone. Genetics. Obesity.
Symptoms: hirsutism (↑hair growth) occurs in 50%> of pts mainly on face, abdomen and chest (may be only
symptom sometimes). Acne may persist beyond teen years. Thinning of scalp hair (similar to male baldness).
Weight gain. Depression. Symptoms usually begin in late teens/early 20s. Not all symptoms occur in all
symptoms, sometimes different combos, also vary from mild to severe.
Complications: ↑risk of type2 diabetes, diabetes in pregnancy, ↑cholesterol level, ↑BP, ↑risk of preemie baby,
↑risk of pre-eclampsia, infrequent/no periods ↑risk of uterine cancer, sleep apnoea.
Tests: blood tests to measure testosterone & LH levels which are ↑in pts. US to detect cysts in slightly enlarged
ovaries. CVD tests such as BP and cholesterol. Annual screening for diabetes.
Treatment: loosing weight decreases insulin levels reducing risk of diabetes/ ↑BP. Hair loss products such as
elfornithine may be prescribed to rub on skin. Medications such as cyproterone acetate an anti-testosterone
helps to reduce hair growth- if not helpful then combined oral contraceptive pill Yasmin (also helps acne and
maintain regular bleeds like periods, or if pt doesn’t want pill then progestin's should be given instead) – meds
need to be taken regularly or hair will recur. Metformin to ↑insulin sensitivity which may reduce insulin levels in
blood. Healthy lifestyle so eat a healthy diet, regular exercise, not smoking and loosing weight. Use clomifene if
pt wants to get pregnant instead.
Breast CA
Breast CA
 B rea s t ca nce r

Epidemiology: affects 1 in 11 women (↑cases in developed countries). Rare in men.

Pathology: non invasive ductal carcinoma-in-situ (CIS) is premalignant & seen as microcalcification on mammography (unifocal or spread). Non-invasive
lobular CIS is rarer & tends to be multifocal. Invasive ductal carcinoma is most common (70%) whereas invasive lobar carcinoma accounts for 10-15%
cases. Medullary cancers (5%) tends to affect younger pts while colloid/mucoid (2%) tend to affect elderly. Others: papillary, tubulary, adenoid-cystic
and paget’s.
Risk factors: family history, age and uninterrupted oestrogen exposure, hence: nulliparity, 1st pregnancy, >30yrs, menarche, late menopause, HRT,
obesity, BRCA genes, not breast-feeding, the pill, past breast cancer.
The pt: lump, nipple discharge/inversion, skin change.
Investigations: all lumps to undergo triple assessment: clinical exam + histology/cytology (higher C number higher metastatic) + mammography/US.
Staging: stage 1: confined to breast stage 2: growth confined to breast, mobile, lymph nodes in ipsilateral axilla stage 3: tumour fixed to muscle (but
not chest wall), ipsilateral lymph nodes matted & may be fixed, skin involvement larger than tumour. Stage 4: complete fixation of tumour to chest wall,
distant metastases.
Treating stage 1-2: surgery: wide-local excision or mastectomy +/- breast reconstruction + axillary node sampling/surgical clearance. Local excision +
radio (80% treated this way) gives equal survival rates but higher recurrence rates than mastectomy. Radiotherapy: if at ↑risk of local recurrence, post-
op radio decreases local recurrence & may ↑overall survival. Radio to axilla used if lymph node +ve on sampling & complete surgical clearance not
performed. SE: pneumonitis, pericarditis, rib fractures, lymphoedema, brachial plexopathy. Chemo: improves survival (esp if young & node +ve in
recurrent disease or as neoadjuvant if large tumour), e.g. an anthracycline (epirubicin is less cardiotoxic than doxorubicin) +5FU + cyclophosphamide
+/- methotrexate. Trastuzudocetaxel are used. Endocrine agents: aim to reduce oestrogen activity, and is used in oestrogen receptor or progesterone
receptor +ve disease. The ER blocker tamoxifen is widely used e.g. 20mg/d PO for 5yrs post-op (may rarely cause uterine cancer so warn to report
vaginal bleeding). Aromatase inhibitor e.g. anastrozole targeting oestrogen synthesis are also used (may be better tolerated). They are often used if
post-menopausal. If pre-menopausal and an ER+ve tumour, ovarian ablation (via surgery or radiotherapy), or GnRH analogues (e.g. goserelin)
↓recurrence and ↑survival. Support: breast care nurses. Reconstruction options: e.g. implants, latissimus dorsi flap, TRAM flap.
Treating distant disease: stage 3-4: assess LFT, Ca2+, CXR, skeletal survey, bone scan, CT/MRI or PET-CT, liver US. DXT to painful bony lesions
(bisphosphonates, may ↓pain and fracture risk). Tamoxifen is often used in ER+ve; if relapse after initial success, consider chemo. Tumours +ve for
HER2 protein metastasizing to brain may respond to monoclonal antibody trastuzmab (Herceptin). CNS surgery for solitary (or easily accessable)
metastases may be possible; if not- radiotherapy. Get specialist help for arm lymphedema (try decongestive methods before compressive methods).
Preventing deaths: exercise, good diet. Promote awareness. Screening: 2-view mammography every 3yrs for women aged 50-70 in UK, MRI may be
better- ↓deaths by 25%. Raloxifene may prevent some ER+ve cancers.
 Dysphagia

Dysphagia is difficulty in swallowing and always needs urgent investigation to exclude malignancy (unless of short duration & associated with
sore throat).
Causes: oral, pharyngeal or oesophageal? Mechanical or motility related?
Clinical features: key 5 questions to ask:
1. Was there difficulty swallowing solids AND liquids from the start? (both together)
Yes: motility disorder (achalasia, neurological), or pharyngeal causes
No: solids THEN liquids: suspect a stricture (benign/malignant
2. Is it difficult to make swallowing movement?
Yes: suspect bulbar palsy, esp if he coughs on swallowing.
3. Is swallowing painful (odynophagia)?
Yes: suspect cancer, oesophageal ulcer/spasm.
4. Is the dysphagia intermittent or constant & getting worse?
Intermittent: suspect oesophageal spasm.
Constant/worsening: suspect malignant stricture.
5. Does the neck bulge/gurgle when drinking?
Yes: suspect pharyngeal pouch.
Signs: is pt cachectic/anaemic? Examine mouth; feel for supraclavicular nodes (left SC node= virchows node- suggests intra-abdominal
malignancy); look for signs of systemic disease e.g. systemic sclerosis, CNS disease.
Investigations: FBC (anaemia); U&E (dehydration), CXR (mediastinal fluid level, absent gastric bubble, aspiration). Upper GI endoscopy (+/-
biopsy) is usually the 1st line investigation. Barium swallow +/- video fluoroscopy is useful to diagnose high dysphagia/dysmotility (e.g.
achalasia). Further tests: oesophageal manometry (if normal barium swallow); ENT opinion if suspected pharyngeal cause.
 Dysphagia co ntinued …

Specific conditions: esophagitis. Diffuse oesophageal spasm causes

intermittent dysphagia +/- chest pain. Barium swallow: abnormal contractions
e.g. cork-screw oesophagus. Achalasia: lower oesophageal sphincter fails to
relax (due to degeneration of myenteric plexus) causes dysphagia, regurgitation,
substernal cramps, and ↓weight. Barium swallow: dilated tapering oesophagus.
Treatment: endoscopic balloon dilatation. Botulinum toxin injection is
alternative if unsuitable for an invasive procedure. Calcium channel blockers &
nitrates also relax sphincter. Longstanding achalasia is a risk factor for
oesophageal cancer. Benign oesophageal stricture: caused by gastro-
oesophageal reflux disease (GORD), corrosives, surgery or radiotherapy.
Treatment: endoscopic balloon dilatation. Oesophageal cancer: associations:
male, GORD, tobacco, alcohol, barretts oesophagus, achalasia, tylosis, Paterson-
brown-Kelly syndrome.
 benign breast lumps

Benign mass is usually 3D, mobile and smooth, has regular borders and is solid/cystic in consistency.
A malignant mass is usually firm in consistency, has regular borders and may be fixed to the underlying skin/soft tissue. May also
be skin changes/nipple retraction.
Differentiation is still not easy and to err in side of safety is wise.
Classification: physiological swelling/tenderness, nodularity, breast pain (not usually associated with malignancy), palpable breast
lumps, nipple discharge including galactorroea, breast infection & inflammation- usually associated with lactation.
Breast are active organs which change throughout menstruation & some degree of tenderness/nodularity is common affecting 50-
60% of all menstruating women- resolves rapidly as menstruation starts- also called mammary dysplasia & cystic mastopathy: 30-
50yo’s tend to be affected, less frequent in association with oral contraceptives (reduce risk of benign breast disease generally) and
rare after menopause, may recur with HRT. Management: reduction/avoid caffeine, vitamin E, pyridoxine, evening primrose oil.
Premature thelarche: early breast growths (or some growth in males) is quite common. Breast are first of secondary sexual
characteristics to develop & may be some early activity in quite young girls: very early development may be asymmetrical and
unilateral- some will show contralateral development, unless premature pubic hair is found then just reassurance is required, not
height and weight in centile start as early puberty accompanies obesity.
Breast lumps in males: boys may display breast development in puberty & again reassure them- common in klinefelters syndrome.
Gynacomastia may accompany a number of disease or result of use of drugs- male breast cancer does occur but rare.
Nodularity: normal, hormonally mediated change with lumpiness of breast & varying degrees of pain & tenderness. Symptoms are
greatest before 1wk of menstruation & when it starts. Exam may reveal area of nodularity/thickening, poorly differentiated from
surrounding tissue & often in upper right quadrant of breast. If changes are bilateral & symmetrical then its rarely pathological, if
asymmetry then review pt after 1-2 menstruation cycle to see her mid cycle. If symptoms persist then refer. Mammography often
used for older pts but for younger pts with denser tissue, use US. Treatment: analgesia and a good bra.
Fibroadenoma
 Fibroadenoma

• This is a benign tumour that is common in young women, mostly aged under 40 years. It is composed of stromal and
epithelial elements and probably represents increased sensitivity to oestrogens:
• Complex and multiple fibroadenomas are associated with a two-fold increase in the risk of breast cancer.
• They represent a hyperplasia or proliferation of a single terminal duct unit.
• Most stop growing at about 2 or 3 cm, but they can enlarge rather further.
• About 10% disappear each year.
• They tend to regress after the menopause.
• They occur in about half of women who receive ciclosporin after renal transplant.
• They are the most common tumour of the breast in those under 30 years old, but overall they are second to breast cancer.
• Juvenile fibroadenomas can occur in teenage girls.
• Both mammography and ultrasound may be used to examine the lump:
• Ultrasound tends to be preferred in younger women with dense breasts, as mammograms are more difficult to interpret in
this group. Routine mammography, as a population screening tool, is not performed below the age of 50 years.
• Imaging studies may fail to give a firm diagnosis and biopsy or excision may be required for peace of mind of both the
patient and doctor.
• If there is confidence in the diagnosis then inactivity may lead to spontaneous regression, but the patient must be advised
to check the lump regularly and to return if it starts to enlarge.
• Assessment often includes examination, imaging studies and fine-needle aspiration.
 STI
History: timing of last intercourse, contraception, partner’s, medical history etc
Examination: Detailed examination of genitalia including nodes, hair. Scrotum,
subprebutial space & male urethra. Pr exam, protoscopy, PV and speculum exam.
Signs: Vaginal/urethral discharge, genital lesions, herpes, syphilis, Chlamydia,
genital warts, saplingitis and lice.
Tests: Refer to GUM clinic. Urine: dipstick, MSU for MC+s. Ulcers: swabs for HSV
culture. Urethral smear for gram stain for N. ghonorrea, same for chlamydia.
Blood tests: Syphilis, hepatitis & HIV serology after counselling.
Follow-up: 1W & 3M- repeat smears, cultures & syphilis serology
 UTI
The presence of pure growth of >10^5 organisms per mL of fresh MSU. Lower UTI: Urethra, bladder, prostate. Upper UTI:
Renal pelvis.

Risk factors: sexual intercourse, exposure to spermicide in female, pregnancy, menopause, ↓host defence, UT obstruction,
stones, catheter & malformation.
Organisms: E.coli is main organism. Also staphylococcus saprophyticus
Symptoms: Acute pyelonephritis: High fever, rigors, vomiting, loin pain and tenderness, oliguria.
Cystitis: frequency, dysuria, urgency, strangury, haematuria, suprapubic pain.
Prostatis: flu-like symptoms, low back-ache, few urinary symptoms, swollen/tender prostate on PR.
Signs: Fever, abdominal/loin tenderness, foul-smelling urine. Occasionally distended bladder, enlarged prostate.
Tests: If symptoms present, dipstick urine: treat empirically if nitrites/leucoytes are +ve while waiting sensitives on an MSU. If
dipstick is –ve, consider sending an MSU for lab MC&S to confirm. Blood tests: FBC, U&E, CRP & blood cultures.
Prevention: Drink more water. Antibiotic prophylaxis(continuously or post-coital). Self treatment with single antibiotic.
Drinking 200-750ml of cranberry/lingo berry juice per d ↓risk of symptomatic recurrent infection in women by 10-20%.
Management: Drink lots of fluid + urinate often.
Women(non preg-bacterial): Lower UTI: trimethoprim PO or nitrofurantroin (normal renal function). Alternative: cephalexin
PO. Upper UTI: cefuroxime IV then oral. Men: quinolone e.g. levofloxacin. Antibiotic therapy of asymptomatic for >65yo
 Gout
Causes: hereditary, ↑dietary purines, alcohol excess, diuretics, leukaemia, cytotoxic’s, renal
impairment.

Associations: gout often marker for other conditions e.g. hypertension, ischaemic heart
diseases and metabolic syndrome > should always check + exclude.

Investigations: light microscopy shows negatively birefringent urate crystals. Serum urate
usually raised.
Treatment(acute): Strong NASID e.g. diclofenac PO.
Prevention: loose weight. Avoid prolonged fasts, alcohol excess, purine-rich foods, low-dose
aspirin. Use allopurinol if recurrent attacks >may trigger an attack so wait 3w after acute
episode and cover with NSAID.
 Thrush-candida albican
Thrush is commonst cause of discharge & classically described as white curds.
The vulva & vagina may be red, fissured and sore. Partner may be asymptomatic.
Risk factors: pregnancy, immunodeficiency's, diabetes, the pill, antibiotics.
Diagnosis: microscopy: strings of mycelium/oval spores. Culture on sabouraud’s
medium.
Treatment: A single imidazole vaginal pessary, e.g. clotrimazole + cream for the
vulva (+partner) is convenient. Alternative: 1dose of fluconazole PO, Reassure
that thrush is not necessarily sexually transmitted.
 Bacterial vaginosis- fishy smell
Causes fishy smelling discharge, vagina is not inflamed. Itch is rare. Vaginal
pH>5.5 hence alteration of bacterial flora and/or overgrowth e.g. of gardenerlla
vaginalis. There is ↑risk of pre-term labour and/or amniotic infection.

Treatment: metronidazole PO or clindamycin cream.

 Ghonorrea
Can infect any columnar epithelium e.g. urethrea/cervix
Male: urethral pus and/or dysuria; tenesumus, proctitis and/or discharge. PR if gay.
Female: often asymptomatic but may have vagina discharge, dysuria, proctitis. Pharyngeal
disease is often asymptomatic.
Complications(local): prostatitis, cystitis, salpingitis, epididymitis, bartholinitis. Systemic:
Septecemia, e.g. with petechiae, hand or foot pustules, arthritis; Reiter’s syndrome. Long
term: urtheral stricture, infertility.
Treatment(non-complicated): ceftriaxone IM single dose or cefixime PO stat, plus treatment
for chlamydia (e.g. doxycline PO. Also spectinomycin IM stat or single dose.
 Diabetes mellitus-
Causes: destruction of islet cells; autoimmune disorder, steroids, cushing disease etc
Signs & symptoms: ketonuria, unexplained weight-loss, usually young, persistant hyperglycaemia despite diet &
medications, presence of autoantibodies & anti-glutamic acid decarboxylase, polyuria (more urination), polydipsia
(↑thirst), visual blurring, genital thrush, >7mmol/L-fasting glucose or random >11.1mmol/L-random. Type 2 is
asymptomatic.
OGTT test- fast overnight, give 75g glucose in 300mL water to drink in the morning, measure venous plasma
glucose before and 2hr after drink.
Treatment: diet, exercise, smoking cessation, care during pregnancy.
Drugs: start statin and control BP.
• Biguanide (metformin) to ↑insulin sensitivity and to help weight. SE: nausea, diarrea & abdominal pain. Stop
if: tissue hypoxia e.g. MI.
• sulfonylura with breakfast to ↑insulin secretion SE: hypoglycaemia, ↑weight. Insulin e.g.
• novorapid may be needed just before main meals.
Complications from diabetes: vascular diseases e.g. MI-chief killer- use statins. Micoalbuminuria from urine
dipstick may suggest early renal disease & ↑vascular risk- protect kidneys e.g. A2A blocker. Diabetic retinopathy-
background retinopathy: microaenurisms(dots), hameoragges(blots) & hard exudates (lipid deposits). Proliferative
retinopathy(new vessels form)- annual fundoscopy/retinal photo for all. Cataracts. Rubeosis iridises: new vessels
on iris, may lead to glaucoma.
 osteoarthritis

Most common joint condition. More common in females 50yrs>

Signs & symptoms: localised disease (usually knee/hip), pain on movement, crepitus, worse at
end of day, background pain at rest, joint gelling-stiffness after rest up to 30mins, joint
instability. Generalised disease: common in post-meno women. DIP, thumb, carpo-metacarpal
joints most affected & knees. May be joint tenderness, derangement & bone swelling, ↓range
of movement.
Investigations: plain radiography shows loss of joint space, subchondral sclerosis, cysts &
marginal osteophytes.
Management: exercises for muscle strength & joint stability e.g. quidricep exercises, keep
active. Regular paracetamol & codeine for pain. Consider NSAIDS if the previous fail. Weight
loss if BMI >28, walking aids, footwear, physio. Intra-articular steroid injections help symptoms
temporarily. Joint replacement-best treatment.
 Osteoporosis
More common in females than males (50yr>)

Risk factors: SHATTERED= S=steroid use, H=hyperthyroidism, A=alcohol&tobacco, T=thin(BMI

<22), T=testosterone↓, E= early menopause, R=renal/liver failure, E=erosive inflammatory
bone disease, D=dietary e.g. Ca↓, DM

Investigations: X-ray, bloods & biopsy.

Management:
Lifestyle- quit smoking/alcohol↓, weight bearing exercise, calcium & vitamin D diet.
Drugs- Bisphosphonates- SE: photosensitivity, GI upset. Calcium & vitamin D., Testosterone.
 Hypertension

Stage 1= 140/90
Stage 2= 160/100

If stage 1, offer ambulatory monitoring, however if they have co-

morbidities (or afro-carribean) then offer treatment.

If stage 2, offer treatment of: ACE-inhibitors (SE: cough) and calcium

channel blockers.
 HTN

HTN is a major risk factor for stroke & MI. it is usually asymptomatic and regular screening (e.g. 3yrly) is a vital primary care
task. It causes ~50% of all vascular deaths. Most preventable deaths are in areas without universal screening.
Isolated systolic HTN (ISH): the most common form of HTN in UK- affects >50% of the over 60s & results from stiffening of large
arteries (arteriosclerosis). It is not benign: doubles risk of MI, triples risk of CVA. Treatment reduces this excess risk & is, if not
more, effective than treating moderate HTN in middle-age pts. ‘Malignant’ or accelerated phase HTN: refers to a rapid rise in
BP leading to vascular damage (pathological hallmark is fibrinoid necrosis). Usually there is severe HTN (e.g. systolic >200,
diastolic >130) + bilateral retinal haemorrhages & exudates; papilledema may or may not be present. Symptoms are common
e.g. headache +/- visual disturbance. Alone it requires urgent treatment. It may also precipitate acute RF, HF or encephalopathy
which are hypertensive emergencies. Untreated: 90% die in 1yr; treated, 70% survive 5yrs. It is more common in younger pts &
in black pts. Look hard for any underlining cause. Essential HTN: (primary cause: unknown) ~95% of cases. Secondary HTN~5%
of cases. Causes include: Renal disease: most common secondary cause. 75% are from intrinsic renal disease:
glomerulonephritis, polyarteritis nodosa (PAN), systemic sclerosis, chronic pyelonephritis, or polycystic kidneys. 25% are due to
renovascular disease, most frequently atheromatous (elderly male smokers, e.g. with peripheral vascular disease) or rarely
fibro0muscular dysplasia (young female). Endocrine disease: Cushing's, and Conns syndromes, phaeochromocytoma,
acromegaly, hyperparathyroidism. Others: Coarctation, pregnancy, steroids, MAOI, ‘the pill’. Signs & symptoms: usually
asymptomatic (except malignant HTN, above). Headache is no more common than ine the general population. Always examine
the CVS fully & check for retinopathy. Are there features of an underlying cause (phaeochromocytoma etc), signs of renal
disease, radiofemoral delay, or weak femoral pulses (coarctation), renal bruits, palpable kidneys, or Cushing's syndrome? Look
for end-organ damage: LVH, retinopathy & proteinuria- indicates severity & duration of HTN & associated with a poorer
prognosis. Tests: to help quantify overall risk: fasting glucose; cholesterol. To look for end-organ damage: ECG (any LV
hypertrophy? Past MI?); urine analysis (protein, blood). To ‘exclude’ secondary causes: U&E, (e.g. K+ ↓in Conn’s); Ca2+ (↑ in
hyperparathyroidism). Special tests: Renal US/arteriography (renal artery stenosis); 24h urinary metanephrines; urinary free
cortisol; renin; aldosterone; MR aorta (coarctation). 24h ambulatory BP monitoring (ABPM) may help sometimes e.g. in ‘white
coat’ or borderline HTN, & is now recommended for all newly diagnosed hypertensive. Ambulatory reading’s are always lower;
add on 10/5mmHg. Echocardiography may be useful to assess end-organ damage (LV hypertrophy).
 Managing suspected HTN

Clinical BP <140/90= Normotensive

Clinical BP >140/90= Offer ABPM- calc CV risk & look for organ damage THEN:
If ABPM <135/85= Normotensive, consider Px if clear end-organ damage or high risk.
If ABPM >135/85= stage 1 HTN, Px if CV risk >20%/10yrs or end organ damage.
If ABPM >150/95= stage 2 HTN, Px.
Lifestyle changes: ↓Concomitant risk factors: stop smoking; low-fat diet. ↓ alcohol & salt intake;
increase exercise; ↓weight if obese.
Drugs: Monotherapy: if >55yrs & in black pts of any age, 1st choice is Ca2+ channel blocker or
thiazide. If <55yrs, 1st choice is ACE-I (or ARB (angiotensin receptor blocker) if ACE-I intolerant
e.g. cough). B-blockers are not 1st line for HTN but consider in younger people, particularly: if
intolerance or CI to ACE-i/ARB exist, or she is a woman of child-bearing potential, or there is
↑sympathetic drive. Combo therapy: ACE-I + Ca2+ channel blocker/diuretic is logical & has
been commonly done in trials. Try ACE-I, Ca2+ channel blocker & thiazide. If BP still uncontrolled
on adequate doses of 3 drugs, add a 4th (consider: higher-dose thiazide, or another diuretic e.g.
spironolactone (monitor U&E), or B-blockers, or selective alpha-blockers) & get help. If only on
B-blocker & a 2nd drug is needed, add Ca2+ blocker, not a thiazide, to ↓risk of developing
diabetes.
 HTN: dose example/SE’s

Thiazides: e.g. chlortalidone PO mane, SE: K+ ↓, Na+ ↓,impotence, CI: gout. Ca2+ channel
blockers: e.g. nifedipine MR, PO, SE: flushes, fatigue, gum hyperplasia, ankle oedema; avoid
short-acting form. ACE-I: e.g. lisinopril PO- may be 1st choice if co-existing LVF, or in diabetics
(esp. if microalbuminuria) or proteinuria, SE: cough, K+ ↑, RF, angio-oedema, CI: bilateral renal
artery/aortic valve stenosis. ARB (angiotensin receptor blocker): Candesartan; caution if valve
disease or cardiomyopathy; monitor K+, SE: vertigo, urticaria, pruritis. Direct renin blockers:
aliskiren; monitor K+, SE: diarrhoea, rash, ↑K+, avoid in CRF, DM & with ACE-I or ARB. B-
blockers: e.g. bisoprolol PO, SE: bronchospasm, HF. Consider aspirin when BP controlled, if
aged >55yrs, add a statin (esp. if other risk factors).
-> most drugs take 4-8w to gain max effect: don’t assess efficacy with just one BP measurement.
Malignant HTN: in general, use oral therapy, unless there is encephalopathy, or CCF. The aim is
for a controlled reduction in BP over days not hrs. avoid sudden drops in BP as cerebral auto
regulation is poor (so stroke risk ↑). Bed rest; there is no ideal hypotensive, but atenolol or
long acting Ca2+ blockers may be used PO. Encephalopathy (headache, focal CNS signs,
seizures, coma): aim to reduce BP to ~110 diastolic over 4h. Admit to monitored area. Insert
intra-arterial line for pressure monitoring. IV Furosemide then either IV labetalol (repeated) or
sodium nitroprusside infusion IVI in 5% glucose- give little over few hrs only to avoid cyanide
risk. -> never use sublingual nifedipine to reduce BP (big drop in BP & stroke risk).
 Down’s syndrome- Trisomy 21
Causes: The baby has an extra chromosome so having 3 copies instead of 2. The
baby also has trisomy 21 which is observed in 1 in 650 live births and is not
geographical or ethnic specific. Incidence= 1:30 for 45yo> mother.

Clinical features: Flat face, slanting eyes, epicanthic folds, small ears, simian crease,
short stubby fingers, hypotonia, variable learning difficulties, congenital heart
disease (up to 50%).

Complications: heart disorders, bowel abnormalities, digestive problems, hearing

and vision impairments, thyroid dysfunctions, infections, cervical spine dislocation
and blood disorders.
Mortality: High in first year but many survive to adulthood.
Turners syndrome
Webbed neck
 Turner’s syndrome
Causes: A female with Turner syndrome has part or all of one X chromosome missing. This
means the girl has just one complete X chromosome rather than two.
Diagnosing: CVS, amniocentesis
Clinical signs: Babies usually have swollen hands and feet (lymphedema) Being shorter than
average, webbed kneck, broad chest & widely spaced nipples, low hair-line, spoon-shaped
nails, may not have fully developed breasts, undeveloped ovaries resulting in lack of monthly
periods and infertility. Heart, kidney, thyroid, bone and ear disorders. May have learning
difficulties.

Associated conditions: Diabetes, GI bleeding, lymphodemia, hypertension.

Treatment: Growth hormone which will prevent short stature during adulthood.
Somatotropin. Ostrogens to trigger breast development and progesterone to help encourage
periods. With hormone replacement therapy, their vagina and womb may develop.
 Klinfelter syndrome- XXY
Cause: do to the chromosome- XXY.

Diagnosing: Blood tests (karyotyping), antenatal screening, amniocentesis.

Signs & symptoms: Psychopathy, learning difficulties, gnyacomastia, sparse facial hair, small
firm testicles,↓Libido and osteoporosis.

Treatment: Testosterone replacement to boost growth of testicles, sex drive mood &
esteem, facial & pubic hair, strength and protect against osteoporosis. Surgery for
gynaecomastia. Speech, language & behavioural therapies for learning difficulties.

Complications: CVD, osteoporosis, breast cancer, diabetes, thrombeoplasm and

autoimmune disease.
Cushings disease
 Marfan syndrome

Signs & symptons: ↓extracellular microfibril formation, lense dislocation, aortic dissection or dilation, dural
ectasia, skeletal features, arachnodactyly (long spidery fingers), armspan>height, pectus deformity, scoliosis,
pes planus. Minor signs: mitral valve prolapse, high-arched palate, joint hypermobility.

Diagnosing: Studying family linkage to causative gene.

Investigations: MRI for dural ectasia, CXR (may show aortic aneurism & unfolding), phnemothorax present in
11% and scoliosis is 70%. ECG. Echocardiography showing mitral valve prolapse & mitral regurgitation in the
majority of pts. CT/CMR for detecting aortic dilation.

Treatment: Danger is aortic dissection- beta-blockers slow dilatation of aortic root. ACE receptor blockers to
inhibit upregulation of TNF- beta. Lifestyle alterations such as those that require prolong exertion at max
cardiac output e.g. marathon. Monitoring with yearly echocardiograms. In pregnancy- risk of aortic dissection
rises.
 Spina bifida

In spina bifida, the vertebral arch of the spinal column is either incompletely formed or absent. The defect can occur anywhere from the base of the skull to
the sacrum. It is most commonly found in the lumbar region. [1] Neurological symptoms and signs generally correspond to the level of the defect. Arnold-Chiari
type II malformation is often associated with myelomeningocele. Here there is cerebellar hypoplasia and displacement of the hindbrain through a widened
foramen magnum. Cerebrospinal fluid (CSF) flow can be disrupted and hydrocephalus can result.
Epidemiology: varies by race. More common in girls. Genetic.
Aetiology: genes and the environment. Shortage of folic acid in diet. Association with maternal diabetes and maternal alcohol exposure. Maternal use of
sodium valproate & carbamazepine- greater risk with valproate.
Presentations: Spina bifida cystica: abnormal herniation of dural sac/neural tissue is evident during antenatal US/at birth. Classically, distruption of spinal cord
function causes dysfunction, flaccid paralysis & areflexia below affected level. Alternative pattern includes preservation of some distal reflex activity which is
usually exaggerated. In cases of meningocele alone, herniation of meninges is often covered by skin so lesion may be more difficult to detect. Imbalanced
muscle forces can lead to spinal deformity, limb contractures & joint dislocations. Arnold-Chiari II malformation may present with stridor or apnoea.
Spina bifida occulta: common & more difficult to detect. Usually no long-term consequence or neuro sequelae. Maybe no cutaneous marker or may be an
obvious abnormality along spine including: fluid-filled cyst mass, an area of hyper/hypo pigmentation, cutis aplasia, congenital dermal sinus, capillary
telangiectasia/haemangioma, hypertrichosis (hairy patch of skin), skin appendages and asymmetrical gluteal cleft, asymmetry of legs/feet, scoliosis or other
spinal deformities, progressive neuro motor and/or sensory deficits can develop with associated bladder/bowel disturbance, may be low back-pain as
individual gets older, sudden onset of pain, motor/sensory & bladder dysfunction can occur after trauma if there is spinal tethering.
Exam: exam spine and note for any deformities. Measure head circumference, assess cry & sucking reflex, assess anal sphincter, exam urinary system, perform
full motor exam, perform full sensory exam. Look for foot and hip deformities.
Investigations: prenatal: raised levels of AFP found at 16-18w found in neural tube defects. 18-20w fetal anomaly screening US. Amniocentesis to check AFP &
acytylcholinesterase. Confirmed spina bifida: bloods for impairments of other organs e.g. renal, urine culture for urinary and bladder impairment. Latex
allergy common in pts. Plain XRAY for scoliosis and hip dysplasia/dislocation. CT/MRI for head and spine scanning for tethering of spinal cord by fibrous bands
and hydrocephalus due to Arnold-Chiari II malformation. Gait analysis.
Management: General: put baby in prone position & cover defect with saline wet dressing. MDT team needed for infant pt. treatment aims to maximise
mobility, prevent complications. Repair of defect: fetal surgery (improve CSF pressure dynamics), close and repair spinal herniation. Those with Arnold-Chiari
II malformation may need suboccipital craniotomy and decompression of the posterior fossa and tonsils if symptomatic. Other: Ongoing holistic management
e.g. physio, physical. Paediatrician assistance. Occupational therapy. Psychological input for individual. Neurosurgical follow up. Bladder & bowel function
maintenance.
Cystica:
 Baby milestones
One month: can lift their head, respond to sound, stare at faces.
2 months: vocalise sounds, follows objects, holds head up for short periods.
3 months: Laughs, holds head steady, recognises your face and scent.
4 months: Holds up head steadily, can bare weight on legs, coos when you talk to him.
5 months: Can distinguish between colours, roll over, amuses himself by playing with hands and
feet
6 months: Turns towards sounds and voices, imitate sounds & blows bubbles and rolls in both
directions.
7 months: Sits without support, reaches for things with a sweeping motion, imitates speech
sounds
8 months: Says “dada” “mama” to distuinguish parents
9 months: Combines syllables in world-like sounds, stands while holding something
10 months: waves goodbye, picks things up with pincer grasp, crawls well, cruises
11 months: stands up alone for a few seconds, plays patty cake
12 months: imitates others activities, jabbers world-like sounds, indicates wants with jestures
 MI- Acute

Take brief history, do quick physical exam and take a 12 lead ECG.

Blood tests: U&E, troponin, glucose, cholesterol, FBC, CXR, (later CCU)

Management: Attach ECG monitor, record 12-lead ECG. O2 2-4L aim for SaO2>95% (caution if
COPD). IV Access: Bloods for FBC, U&E, glucose, lipids, cardiac enzymes.

Brief assessment: History of CVD, risk facors for IHD. Contraindications to thrombolysis? Exam:
pulse, BP (both arms), JVP, cardiac murmers, signs of heart failure, upper limb pulses, scars from
previous cardiac surgery.

Treatment: Aspirin (unless already given), Morphine IV + antiemetic, e.g. metoclopramide IV,
GTN sublingually 2 puffs or 1 tablet as required, primary PCI or thrombolysis, B-blocker e.g.
atenolol IV (unless asthma/left ventricular failure), CXR: do not delay thrombolysis while waiting
unless suspected aneurysm (e.g. inerscapular pain; BP different each arm), consider DVT
prophylaxis, continue medication except sodium channel antagonists.
 Depression- ICD10
Key symptoms: persistent sadness/low mood, loss of interest/pleasure,
fatigue/low energy. At least one of these, most days, most of the time for at least
2 weeks. If any of the previous mentioned, ask about associated symptoms:
Disturbed sleep, poor concentration/indeciveness, low self-confidence,
poor/increased appetite, suicidal thoughts/acts, agitation/slowing of
movements, guilt or self-blame.
 Hypothyroidism
Common=4/1000/yr. If treated prognosis is excellent, if not then diasterous (e.g. heart disease, dementia). As it is
insidious, both you and pt may not realise anything wrong so be alert to subtle nonspecific symptoms, particularly in
women >40yrs old.
Symptoms: Tired, sleepy, lethargic, mood ↓,Cold-disliking, memory/cognition ↓, weight ↑, constipation,
menorrhagia, hoarse voice, dementia, myalgia, cramps & weakness.
Signs: Bradycardic: reflexes relax slowly, axtia (cerebellar), dry thin hair/skin, yawning/drowsy/coma, cold hands +
Temp ↓, ascites +/- non pitting oedema (lids;hands;feet) +/- pericardial/pleural effusion, round puffy face/double
chin/obese; defeated demeanour, immobile +/- ileus, CCF. Also neuropathy, myopathy, goitre.
Diagnosis: ↑TSH; T4 ↓, cholesterol & triglyceride ↑; macrocytosis
Autoimmune causes of primary: Primary atrophic hypothyroidism (diffuse lymphocytic infiltration of the thyroid,
leading to atrophy, hence no goitre). Hashimoto’s thyroiditis: Goitre due to lymphocytic & plasma cell infiltration.
Other causes: iodine difiency, drug-induced etc.
Treatment: healthy & young: levothyroxine (T4) PO; review at 12w. Adjust 6 weekly by clinical state & to normalize
but not suppress TSH. Once normal, check TSH yearly. Enzyme inducers ↑metabolism of levothyroxine.
Elderly/ischaemic heart disease: ↑dose according to TSH. Amidodarone (iodine-rich drug)
 Acidosis-lactic

Causes: cardiopulmonary failure, tissue ichaemia, effects of drugs/toxins/severe illness/prolonged exercise.

History: Infection, cardiorespiratory disease, abdominal complaints, trauma, exposure to toxins, over-dose/self poisoning.

Exam: Looks for signs of hypovolaemic, cardiogenic, septic/toxic shock. To classify lactic acidosis- look for signs of tissue hypoperfusion such as hypertension, tachypnoea,
peripheral shutdown (check capillary refill) and oliguria. Look for evidence of a septic focus & hyperthermia/hypothermia. Kussmauls breathing (rhythmic, deep gasping b
indicates severe acidosis.

Investigations: ABG will reveal a metabolic acidosis (pH <7.35 with low or minimal pCO2) & electrolytes reveal a low plasma bicarbonate (<22 mmol/L). Anion gap (elevate
acidosis). `

Differentials: Diabetic ketoacidosis, other organic acidosis, renal failure, alcoholic ketoacidosis, drug toxicity.

Management: main principles: diagnose & correct underlining cause. Restore adequate O2 delivery to tissues.

Emergency management: Check ABC- immediate resus if indicated. Put pt on SaO2 monitor. Give 100% O2. Consider intubation & ventilator support for pts with deteriora
(take senior advice). Obtain IV access & give a fluid bolus of crystalloid or colloid if tachycardia, hypotension/signs of hypoperfusion such as poor capillary refil is present.
failure is suspected be cautious about fluid infusion- put pt on cardiac monitor as there is predisposition to arrhythmia (refer urgently to acute care team). Arrange transfe
dependency area ASAP.

Furthermore management: Dichloroacetate may be used to stimulate pyruvate dehydrogenase. Carbicarb is a promising buffer. Diaylisis.
PDA
 patent ductus arteriosus

Risk factors: preemie (perinatal asphyxia usually delays rather than fix closure), born at high
altitude also at risk of atrial septal defect. Congenital rubella syndrome, fetal alcohol syndrome and
maternal use of phenytoin and amphetamines.
History: asymptomatic, preemie or RDS. Failure to thrive. Gross congestive heart failure= rare.
Exam: about 1/3 are small for age. If pulmonary circulation overloaded there will be tachycardia,
tachypnoea & wide pulse pressure. The apex is displaced laterally & may be thrill in suprasternal
notch or in left infraclavicular region. First heart sound is normal but second sound is often
obsecured by murmer. Murmer: caused by turbulent flow. More gross the turbulence the louder
the murmer. Machinery murmur. Murmer best heard in left upper chest. If left to right blood flow
ratio exceeds 2:1 there may be mitral rumble from high flow rate across the mitral valve. There is
often an ejection murmur too. These last features will be absent in narrow PDA. Peripheral pulses
are bounding as run off off into pulmonary circulation drops diastolic pressure & causes a wide
pulse pressure. In the low birth-weight preemie- classical signs absent~continuous murmur rarely
heard. There may be rough systolic murmur along left sternal border but a small baby with a large
PDA & significant pulmonary over-circulation may have no murmur. Precordial activity is increased
and peripheral pulses are bounding. The increased precordial activity is caused by large left
ventricular stroke volume.
Differentials: coronary artery fistula, fallots tetralogy, aneurysm of sinus valsalva, aortopulmonary
septal defect, venous hum, atrioventricular malformation.
 PDA continued…

Investigations: if shunt is significant- CXR will show enlargement of pulmonary arteries, veins, left atrium & left
ventricle. In older people, PDA may be calcified and visible on a plain film. Diagnosis confirmed by 2-dimensional
echocardiography. Typically PDA connects junction of main pulmonary artery & left pulmonary artery with aorta just
below & opp left subclavian artery. There is continuous flow from aorta to main pulmonary artery although rate of
flow is variable- shown by doplar echocardiography. In diastole there may be reversal of flow from aorta back into
PDA. ECG may often be normal but with marked extra flow there may be signs of left ventricular hypertrophy with a
tall R in V6. in preemie with large shunt there may even be a T wave inversion & ST depression suggesting ischemia
from high workload.
Management: preemie usually treated with IV indomethacin- results may temporary & surgery still required (high
risks). B-type natriuretic peptide (BNP) can be used to guide treatment. If the child 1yr> then cardiac catheterisation.
Amplatzer PDA device easier to implant & more reliable then occluding coils. Pts who have cardiac catheter closure
of PDA are usually sent home same day however if thoracotomy is required then 2-3d stay required + further if
complications arise. Children who have had PDA closed need no further restrictions on their lives. Whilst PDA
present, risk of endocarditis is high.
Complications: endocarditis, cardiac failure, obstruction of pulmonary vessels & rupture of aorta. Necrotising
enterocolitis. Preemie with PDA at greater risk of bronchopulmonary dysplasia.
Prognosis: preemie with PDA is at risk of bronchopulmonary dysplasia- if child also has IRDS then adverse prognosis
sign; however if uncomplicated, timing of PDA closure is normal. Most pts who have had successful closure of PDA
have no further complications.
Preventions: infants weighing less than 1000g, prophylactic NSAID may aid closure & reduce risk of subsequent
morbidity. However, no evidence of long-term benefit.
 At rial s ep tal de fec t (A SD )

Top right CT demonstrates ASD. CXR shows dilated pulmonary arteries (white wirey stuff on left) due to ASD.
 Atrial Septal defect

A hole connects the atria. Ostium secundum defects (high in septum) are commonest; ostium
primum defects (opposing endocardial cushions) are associated with AV valve anomalies.
Primum ASDs present early. Secundum ASDs are often asymptomatic until adulthood, as the L-
>R shunt depends on compliance of right and left ventricles- (latter decreases with age esp if
BP ↑), so augmenting L->R shunting (hence dyspnoea/heart failure, e.g. at age 40-60). There
may be pulmonary hypertension, cyanosis, arrhythmia, haemoptysis and chest pain.
Signs: AF, ↑JVP, wide, fixed split S2; pulmonary ejection systolic murmur. Pulmonary
hypertension may cause pulmonary or tricuspid regurgitation. ↑freq of migraine.
Complications: reversal of left to right shunt, i.e. Eisenmengers complex: initial L->R shunt
leads to pulmonary hypertension, hence shunt reversal, causing cyanosis (+/- heart failure &
chest infections). Paradoxical emboli (vein-> artery via ASD; rare)
Tests: ECG: RBBB with LAD and prolonged PR interval (primum defect) or RAD (secundum
defect). CXR: small aortic knuckle, pulmonary plethora, progressive atrial enlargement.
Echocardiography is diagnostic. Cardiac catheterisation shows step up in O2 sat in right atrium.
Treatment: in children closure is recommended before age 10yrs. In adults, if symptomatic, or
if pulmonary to systemic blood flow ratios of >1.5:1. transcatheter closure is now more
common than surgical.
 Vent ric ula r s e pta l de fec t

CXR shows cardiomegaly with R one showing plethoric lungs.

 ventricular septal defect

A whole connects the ventricles. Causes: congenital (prevalence 2:1000 births); acquired (post-
MI).
Symptoms: may be present with severe heart failure in infancy, or remain asymptomatic & can be
detected incidentally in later life.
Signs: these depend on size and site: smaller holes, which are haemodynamically less significant,
give louder murmurs. Classically, harsh pansystolic (heard continuously so woosh woosh- whereas
ejection mumur= woosh then either lub/dub) murmur is heard at the left sternal angle, with a
systolic thrill +/- left parasternal heave. Larger holes are associated with signs of pulmonary
hypertension.
Complications: AR, infundibular stenosis, IE/SBE, pulmonary hypertension, Eisenmenger’s
complex.
Tests: ECG: normal (small VSD), LAD + LVH (moderate VSD), or LVH + RVH (large VSD). CXR: normal
heart size +/- mild pulmonary plethora (small VSD) or cardiomegaly, large pulmonary arteries &
marked pulmonary plethora (large VSD). Cardiac catheter: step up in 02 sat in right ventricle.
Treatment: this is medical, at first, as many close spontaneously. Indications for surgical closure:
failed medical therapy, symptomatic VSD, shunt >3 : 1 SBE/IE. Endovascular closure is also
possible.
Angina
 Angina

Due to myocardial ischemia and presents as a central chest tightness or heaviness, which is brought on by exertion & relieved by
rest. It may radiate to one or both arms, the neck, jaw or teeth. Other precipitants: emotion, cold weather, heavy meals.
Associated symptoms: dyspnoea, nausea, sweatiness, faintness.
Causes: mostly atheroma. Rarely: anaemia, AS, tachyarrythmias; HCM; arteritis/small vessel disease (microvascular angina/cardiac
syndrome X)
Types of angina: stable angina: induced by effort, relieved by rest. Unstable angina: angina of increasing frequency/severity; occurs
on minimal exertion/at rest; associated with ↑ ↑risk of MI. Decubitus angina: precipitated by lying flat. Variant angina: caused by
coronary artery spasms (rare; may co-exist with fixed stenosis)
Management: modify risk factors: stop smoking, encourage exercise/weight loss. Control hypertension, diabetes etc. if total
cholesterol >4mmol/L give a statin. Aspirin reduces mortality by 34%. B-blockers e.g. atenolol PO, reduce symptoms unless CI
(asthma, COPD, LVF, bradycardia, coronary artery spasm). Nitrates: for symptoms, give GTN spray/sublingual tabs upto every half
hr. prophylaxis: give regular oral nitrate e.g. isosorbide mononitrate PO bd. Alternatives: adhesive nitrate skin patches or buccal
pills. SE: headaches, BP ↓. Long acting calcium agonists: amplodipine diltiazem-MR PO. They are particularly useful if there is a CI
to B-blockers. K+ channel activator e.g. nicorandil PO, if still not controlled. Others: ivabradine inhibits the pacemaker current in
the SA node & thus reduces heart rate. Useful in those who cannot take B-blocker, having similar efficacy. Trimetazidine inhibits
fatty acid oxidation, leading the myocardium to use glucose, which is more efficient. Ranolazine inhibits the late Na+ current.
Indications for referral: diagnostic uncertainty, new angina of sudden onset; recurrent angina if past MI or CABG; angina
uncontrolled by drugs; unstable angina. Percutaneous transluminal coronary angioplasty (PTCA) involves balloon dilatation of
stenotic vessels. Indications: poor response/tolerance to medical therapy; refractory angina in pts not suitable for CABG; previois
CABG; post thrombolysis in pts with severe stenosis, symptoms/positive stress tests. Stenting reduces restenosis rates & need for
bailout CABG compared with angioplasty. Complications: restenosis, emergency CABG. >70% of angioplasties should be
accompanied by stenting. Antiplatelet agents e.g. clopidogrel reduce risk of stent thrombosis & IV glycoproteins reduce procedure
related ischemic events. Drug coated stents reduce restenosis rates but at risk of increased late in-stent thrombosis. Long-term
treatment with aspirin & clopidogrel may reduce risk.
HF
 Heart failure (types)

Definition: cardiac output is inadequate for bodies requirements. Prognosis is poor with 25-50% of pts dying within 5yrs of diagnosis.
Prevalence: 1-3% of the general population ~10% among elderly.
Systolic verses diastolic failure: systolic failure: inability of ventricles to contract normally, resulting ↓cardiac output. Ejection fraction
(EF) is <40%. Causes: IHD, MI, cardiomyopathy. Diastolic failure: inability of ventricles to relax & fill normally, causing ↑filling
pressures. EF is >50%. Causes: constrictive pericarditis, tampdonade, restrictive cardiomyopathy, hypertension. NB: systolic and
diastolic failure usually co-exist.
Left sided versus right-sided failure: left ventricular failure (LVF) and right ventricular failure (RVF) may occur independently, or
together as congestive cardiac failure (CCF). Left ventricular failure: symptoms: dyspnoa, poor exercise tolerance, fatigue, orthopnoea,
paroxysmal nocturnal dyspnoea (PND), nocturnal cough (+/- pink frothy sputum), wheeze (cardiac ‘asthma’), nocturia, cold
peripheries, weight loss, muscle wasting. Right ventricular failure: causes: LVF, pulmonary stenosis, lung disease. Symptoms:
peripheral edema (up to thighs, sacrum, abdominal wall), ascites, nausea, anorexia, facial engorgement, pulsation in neck and face
(tricuspid regurgitation), epixtaxis.
Acute versus chronic heart failure: acute heart failure is often used exclusively to mean new onset acute/decompensation of chronic
heart failure characterized by pulmonary and/or peripheral edema with/without signs of peripheral hypoperfusion. Chronic heart
failure develops or progresses slowly. Venous congestion is common but arterial is well maintained until late.
Low-output versus high-output failure: low-output heart failure: cardiac output is ↓and fails to ↑normally with exertion. Causes:
pump failure: systolic and/or diastolic HF, ↓heart rate (e.g. B-blockers, heart block, post MI), negatively inotrophic drugs (e.g. most
antiarrhythmic agents). Excessive pre-load: e.g. mitral regurgitation or fluid overload (e.g. NSAID causing fluid retention). Fluid
overload may cause LVF in a normal heart if renal excretion is impaired or big volumes are involved (e.g. IVI running too fast). More
common if there is simultaneous compromise of cardiac function, and in the elderly. Chronic excessive overload: e.g. aortic stenosis,
hypertension. High-output heart failure: this is rare. Here, output is normal or increased in face of ↑ ↑needs. Failure occurs when
cardiac output fails to meet those needs. It will occur in normal heart but even earlier if there is heart disease. Causes: anemia,
pregnancy, hyperthyroidism, pagets disease, arteriovenous malformation, beri beri. Consequences: initially features of RVF; later LVF
becomes evident.
 Heart failure investigations/signs/prognosis

Chronic heart failure: stop smoking, eat less salt. Optimize weight & nutrition. Treat the cause (e.g. dysrhythmias; valve disease).
Treat exacerbating factors (anemia, thyroid disease, infection, ↑BP). Avoid exacerbating factors e.g. NSAIDs (fluid retention) &
verapamil (-ve inotrope). Drugs:
1. Diuretics: diuretics can reduce the risk of death and worsening heart failure. Give loop diuretics to relieve symptoms e.g.
furosemide PO. Increase dose as necessary. SE: K+ ↓, renal impairment. Monitor U&E and add K+ sparing diuretic (e.g.
spironolactone) if K+ <3.2mmol/L, predisposition to arrhythmias, concurrent digoxin therapy (↓K+ increases risk of digoxin
toxicity), or pre-existing K+ losing conditions. If refractory edema, consider adding a thiazide, e.g. metolazone PO.
2. ACE-I: consider in all those with left ventricular systolic dysfunction; improves symptoms and prolongs life. If cough is a
problem- give angiotensin receptor blocker e.g. candesartan. SE: K+ ↑.
3. B-blockers e.g. carvedilol decreases mortality in heart failure. These benefits appear to be additional to those of ACE-I in pts
with heart failure due to LV-dysfunction. Initiate after diuretic & ACE-i. use with caution: start low and go slow if in doubt
seek specialist advice e.g. carvedilol ->increase dose slowly, wait >2wks between each dose increment.
4. Spironolactone: PO ↓mortality by 30% when added to conventional therapy. Use in those still symptomatic despite optimal
therapy as listed above. It improves endothelial dysfunction. (↑NO bioavailability) and prevents remodelling.
Spironolactone is K+ sparing, but there is little risk of significant hyperkalaemia, even when given with ACE-i.
5. Digoxin helps symptoms even in those with sinus rhythm; and should be considered for pts with LV systolic dysfunction who
have signs or symptoms of heart failure while receiving standard therapy, including ACE-I & B-blockers, or in pts with AF. PO.
Monitor U&E, maintain K+ at 4-5mmol/L. digoxin levels. Other inotropes are unhelpful in terms of outcome.
6. Vasodilators: the combo of hydralazine (SE: drug-induced lupus) & issorbide dinitrate should be used if intolerant of ACE-I
& ARBs as it reduces mortality. It also reduces mortality when added to standard therapy (including ACE-i) in black pts with
heart failure.
 Heart failure contin ued…

Intractable heart failure: reassess the cause. Are they taking the drugs? – at max dose?
Switching furosemide to bumetanide might help: absorption may be better. Consider
admitting for:
• Strict bed rest +/- Na+ & fluid restriction (<1.5L/24H PO)
• Metolazone and IV furosemide
• Opiates and IV nitrates may relieve symptoms
• Weight daily. Do frequent U&E (beware K+ ↓)
• DVT prophylaxis: heparin + TED stockings
In extremis, try IV inotropes (may be difficult to wean pt off them). Consider a heart
transplant- planted into LV. A graft takes the blood to the descending aorta- making
surgery hazardous.
Palliation: treat/prevent comorbidities (e.g. flu vaccine). Good nutrition (allow alcohol).
Involve GP: continuity of care & discussion of prognosis is much appreciated. Dyspnoea,
pain (from liver capsule stretching), nausea, constipation, and ↓mood all need tackling.
Opiates help pain and dyspnoea. O2 may help.
Acute coronary synd- ST elevation
 Acute coronary syndrome- with ST elevation

Includes unstable angina stem1 and NSTEMI. STEMI is a common medical emergency, and prompt
appropriate treatment saves lives. If In doubt seek immediate help.
Initial treatment: take brief history, do a quick physical exam and take a 12 lead ECG. Blood tests on
admission: U&E, troponin, glucose cholesterol, FBC, CXR (later CCU).
Aspirin PO, consider clopidogrel too. Morphine IV (repeat after 5min if necessary). Give antimetic with
the 1st dose of morphine: metoclopramide IV (1st line), cyclizine IV (2nd line). GTN 1-2tablets SL/spray.
O2 must be given for the 1st few hrs after acute MI by mask/nasal prongs. Restore coronary perfusion
either primary PCI (if available) or thrombolysis. Primary PCI now the treatment of choice if ongoing
ischemia and presentation is within 12h. However, not available in all locations. Thrombolysis reduces
steadily from onset of chest pain so start ASAP (target <30min from admission). Thrombolysis CI beyond
24h from time of onset of symptoms/ do not thrombolyse ST depression alone, T-wave inversion alone
or normal ECG.
Complications: recurrent ischemia/failure to reperfuse (usually detected as persisting pain and ST-
segment elevation in immediate aftermath thrombolysis: analgesia, GTN, B-blocker, consider re-
thrombolysis, or PCI. Stroke. Pericarditis: analgesics, try to avoid NSAIDS. Cardiogenic shock.
Right ventricular infarction: confirm by demonstrating ST elevation in Rv3/4 and/or echo. NB: rV4
means that V4 is placed in right 5th intercostal space in Mid clavicle line. Treat hypotension & oliguria
with fluids (avoid nitrates & diuretics). Monitor BP carefully, & assess early signs of pulmonary edema.
Intensive monitoring and inotropes may be useful in some pts.
 Pericarditis

Typical water bottle heart on CXR.

 Pericarditis

Inflammation of pericardium. May be idiopathic or secondary to: viruses,

bacteria, fungi, MI, drugs: procainamide, hydralazine, penicillin, cromolyn
sodium, isoniazid. Others: uraemia, rheumatoid arthritis, SLE, myxoedema,
trauma, surgery, malignancy, radiotherapy, sarcoidosis.
Clinical features: central chest pain worse on inspiration/lying flat +/- relief by
sitting forward. A pericardial friction rub may be heard. Look for evidence of a
pericardial effusion/cardiac tamponade. Fever may occur.
Tests: ECG classically shows concave (saddle-shaped) ST segment elevation, but
may be normal/non-specific (10%). Blood tests: FBC, ESR, U&E, cardiac enzymes
(troponin may be raised), viral serology, blood cultures, if indicated: antibodies,
fungal precipitins, thyroid function tests. Cardiomegaly on CXR may indicate
pericardial effusion- if suspected do Echo.
Treatment: Analgesia e.g. ibuprofen PO with food. Treat cause. Consider
colchicine before steroids/immunosupressants if relapse or continuing symptoms
occur. 15-40% do recur. Steroids may ↑risk of reccurance.
Cardiac tamponade
 Cardiac tamponade

Top left pic shows heart before and after pericardiocentesis. CXR looks similar to pericardial effusion.
 C ard ia c ta mp ona de

Essence: pericardial fluid collects -> intra-pericardial pressure rises -> heart
cannot fill -> pumping stops.
Causes: trauma, lung/breast cancer, pericarditis, MI, bacteria e.g. TB. Rarely: urea
↑, radiation, myxoedema, dissecting aorta, SLE. Also coronary artery dissection
and/or ruptured ventricle.
Signs: falling BP, a rising JVP, and muffled heart sounds, JVP ↑ on inspiration,
pulses paradoxus (pulses fade on inspiration). Echocardiography may be
diagnostic. CXR: globular heart; left heart border convex/straight, right
cardiophrenic angle <90degrees. ECG: electrical alternans. Engorged
veins/pulsating face.
Management: can be very difficult- request senior at bedside. Prompt
pericardiocentesis brings swift relief. While waiting this, give O2, monitor ECG, set
up IVI. Take blood for group & save. Cardiothoracic surgery may play a role: CABG,
ventricular repair/pericardial window- as definitive solution to some causes.
A few things about the upper limb…
Injured to the…

Radial=Wrist drop Ulnar=claw hand Median=ape hand

Everything in posterior= radial nerve

 Carpel tunnel syndrome
Median nerve & 9 tendons compete for space in wrist- compression most common with
woman who have narrower wrists but similar-sized tendons to men etc.
palmar cutaneous branch of median nerve is not affected.

Patient: aching pain in hand & arm(esp at night) & paraesthesiae in thumb, index and middle
fingers, all relieved by dangling the hand over edge of bed & shaking it. Maybe sensory loss
& weakness of abductor pollicis brevix + wasting of thenar eminence. Sweating maybe
impaired.

Associations: pregnancy, diabetes mellitus, rheumatoid, hypothyroidism, renal dialysis,

trauma, acromegaly.
Tests: neurophysiology helps by confirming lesion site & severity. Maximal wrist flexion for
1min(phalens test) may elicit symptoms. Tapping over nerve at wrists induces tingling (Tinel’s
test)
Treatment: splinting, local steroid injection, decompression surgery.
 Ulnar neuropathy

C7-T1. ulnar nerve vulnerable to elbow trauma.

Signs: weakness/wasting of medial (ulnar side) wrist flexors, interossei (cannot cross fingers in the good luck
sign.) and medial two lumbricals (claw hand); hypothena eminence wasting (weak little finger abduction);
sensory loss over medial (ulnar) 1 ½ fingers and ulnar side of hand. Flexion of 4th & 5th DIP joints is weak. With
lesions at the wrist (digitorum profundus intact) , claw hand is more marked.
Asks for trouble in at least 5 places at the elbow, starting proximally at the arcade of struthers (a
musculofascial band~ 8cm proximal to medial epicondyle, and ending distally where it exists the flexor carpi
ulnaris muscle in the forearm. Most often, compression occurs at the epicondylar groove or at the point where
the nerve passes between 2 heads of flexor carpi ulnaris. Truama can easily damage the nerve against its bony
confines (the medial condyle of the humerus- the funny bone). Normally, stretch and compression forces on
the ulnar nerve at the elbow are moderated by its ability to glide in its groove. When normal exurcison is
restricted, irritation ensues. This may cause a vicious cycle of perineural scarring, a consequent loss of
exurcison, and progressive symptoms- without antecedent trauma. Compressive ulnar neuropathies at wrist
(Guyon’s canal- between the pisiform and hamate bones) are less common, but they can result in disability.
Treatment: centres on rest and avoiding pressure on nerve but if symptoms continue, night-time soft elbow
splinting (to prevent flexion >60degrees) is warranted e.g. for 6months. A splint for hand may prevent perm
clawing of fingers. For chronic neuropathy associated with weakness, or if splinting fails, a variety of surgical
procedures have been tried. For moderately severe neuropathies, decompressions in situ may help, but often
fail. Medial epicondylectomies are effective in <50% (but many will recur). Subcutaneous nerve re-routing
(transposition) may be tried. Intramuscular and submuscular transpositions are more complicated- but latter
may be preferable.
Thoracic outlet syndrome
 Thoracic outlet syndrome

Top L pic of MRI showing compression of subclavian artery.

 Thoracic outlet syndrome

Over 90% TOS cases are neurogenic whereas 3-5% is venous. <1% arterial. More common in women than men with 3-9 fold.
History: neurogenic: painless wasting of muscles in hand resulting in weakness e.g. difficulty grasping a racket. Numbness or tingling of the upperlim
Symptoms often vague and generally may affect whole arm. May also be a painful neck and headache. If there is compression of autonomic nerves,
swelling of arm, distension of veins or a diffuse pain in the arm/hand. If subclavian artery compressed pt may notice colour changes, claudication or
arm/hand. Early symptoms may be ignored and pts may not seek medical advice until condition get worse, with development of ulceration/gangren
rare and pts often present with symptoms indicative of more than 1 type. Often history of trauma- may be whiplash from road-traffic accident. It occ
sportsmen, especially swimmers and throwers. The interval between trauma and symptoms may be hrs to weeks.
Examination: most common test is addisons manoeuvres: head is extended and bent to one side and pt takes a deep breath & holds it, followed by
stretch/tether the brachial plexus and/or artery between the anterior and middle scalenes- position held for 15-30s while examiner checks for onset
obliteration of the pulse. Symptoms have been reported both to the side of bending, more commonly to opp side. If symptoms occur on side of ben
consistent with spurlings sign for diagnosis of cervical radiculopathy. Some clinicians ask pt to head forward while maintaining tests position, causing
to contract against plexus to enhance stress effect. Hyperabduction of arm test also used to stress outlet- often causing symptoms & loss of pulse ev
people and may be misleading. Costoclavicular bracing reduces the space between clavicle and first rib & may reproduce symptoms. The elevated ar
sensitive. The upper extremity is held in the ‘hands up’ position with arms abducted and elbows flexed at 90degrees for 3mins, while pt vigorously fl
fingers. A positive sign if pt cannot complete the full 3mins- test is demanding even in normal ppl so its application is limited. The upper chest wall m
asymmetrical after a previous fracture of clavicle. A non-tender, hard mass over the middle third of the clavicle is typical. A fracture that failed to un
callus can cause direct compression of the plexus. Pressure on the clavicle can produce or aggravate symptoms on an ununited fracture. Motion can
the fragments.
Aetiology: cervical ribs or fibrous bands are just one feature that predisposes to narrowing and compression at the outlet. Poor posture can produce
problems. Sometimes people who are depressed/have bad habit where they let head droop forwards allows thoracic outlet to narrow and compress
structures. Large breasts can pull the chest wall forward and cause symptoms. Reduce mammoplasty may have beneficial effect. Sometimes the cau
excessively artificial large breasts. Trauma can move structures in the shoulder and chest wall. Fracture of clavicle can cause compression by bone fr
callus, haematoma or psudeoaneyrism. Some typical precursors of myofascial pain can cause this syndrome: sleep disorder, oestrogen/thyroid defici
inflammatory disease including rheumatoid arthritis, fibromyalgia and disorders of posture such as kyphosis and scoliosis. Necessary to exclude thro
and nerve entrapment in other places: pancoasts syndrome- where lung cancer infiltrates brachial plexus. Paget-schrotter syndrome is thrombosis o
vein following heavy exercise of upper limb.
 Thoracic outlet syndrome
continued…
Differentials: Acromioclavicular joint injury, Brachial plexus injury, Cervical disc injuries, Cervical discogenic pain
syndrome, Cervical radiculopathy, Clavicular injuries, Elbow and forearm overuse injuries, Shoulder impingement
syndrome, Thoracic disc injuries, Thoracic discogenic pain syndrome.
Investigations: blood test to exclude other conditions. CXR: cervical bands with fibrous bands with them. May also show:
elevated first ribs, caused by tight anterior/middle scalene muscles. Displaced fracture of clavicle, non-union and
excessive callus may be apparent. Cervical spine degenerative changes may be causing neck/shoulder pain or
impingement of the spinal nerve roots. Exclude a malignant lesion in the chest. MRI and CT can distinguish cervical root
injury from degenerative spurs, herniated discs or other causes. Adjunctive tests such as CT angiography can be helpful.
Doppler and plethysmography studies can show impediment of blood flow. A near complete cut off of flow during stress
manoeuvre with reproduction of symptoms would be most impressive. Occlusion can occur in normal subjects but is
unusual & not related to age. Angiography and venography can show blockage of vessels from thrombi/emboli.
Angiography can demonstrate aneurisms that may be compressing the plexus and causing neurological features.
Treatment: conservative treatment is first-line. Rehab may help to decompress outlet. Occupational therapy may help
for back protection techniques & better working practices. Injection of trigger points & associated muscles may be
necessary. NSAIDs. Calcium channel blocker when there is vascular instability. Early surgical intervention may prevent
degeneration of brachial plexus- risky. Decompression with neurolysis of the involves regions of brachial plexus especially
C7, C8 and T1 nerve roots. Removal of excessive callus from clavicle fracture; fixation of fracture that has failed to unite
may be required. Breast reduction may be required.
Prognosis: generally good.
Complications: chronic pain, loss of function, depression, neurological complications,
thrombosis/ischemia/pseudoaneyrsm, post-thrombotic syndrome of the lower limb following DVT well recognised;
thrombosis of upper arms can occur too.
Tarsal tunnel syndrome
 Tarsal tunnel syndrome

A compression of the posterior tibial nerve as it passes in the anatomical tarsal tunnel, which lies posterior to medial malleolus &
beneath the retinaculum of the flexor muscles of the foot.
Anterior tarsal tunnel= compression of deep peroneal nerve= rare, causes pain/weakness/sensory changes of foot and ankle.
Distal tarsal tunnel= compression of first branch lateral plantar nerve= presents with heel pain.
Aetiology: often caused by osteoarthritis, post-traumatic ankle deformities/ rheumatoid arthritis/diabetes. Compression may also
result from cyst, lipoma, ganglion, exostosis or neoplasms within tarsal tunnel. People with severely flat feet risk at ↑risk of tarsal
tunnel. Trauma to ankle.
Symptoms: when entrapment compresses nerve it causes ankle pain, numbness, burning sensation, numbness & tingling on sole of
foot. Symptoms usually unilateral and may be worse at night. Pain normally aggravated by prolonged standing/walking, worsens as
day progresses & relieved by rest/elevation/massage. Pain may radiate along sole of foot, sometimes up into calf/ aggravated when
ankle placed in extreme dorsiflexion.
Signs: tinels sign (radiating pain following nerve percussion behind medial malleolus) over tibial nerve at ankle. Manual compression
for 30s may also reproduce symptoms. Wasting of intrinsic muscles in medial aspect of foot & sensory impairment over the sole. 2-
point discrimination sensory testing may indicate which branch of plantar nerve is compressed.
Differntials: most common cause is plantar fasciitis. Achilles tendonitis associated with posterior heel pain. Calcaneal stress fractures
likely in athletes who participate in sportsthat require running/jumping. Heel pad atrophy- esp in older pts. Lumbar intervertebral
disc prolapse.
Investigations: diagnosis usually clinical. Electromyogram (EMG) & nerve conduction studies. MRI to ID underlying lesions & specific
site of compression.
Management: conservative: arch supports and wider shoes may successfully relieve discomfort. NSAIDs if inflammation. Steroid
injections. Orthotics for flat feet. Surgery: (when conservative treatment fails) decompression by section of flexor retinaculum.
Tarsal tunnel release.
Prognosis: surgical release improves/resolves symptoms in 85-90% cases.
 Radial nerve compression

C5-T1. this nerve opens the fist. May be damaged by compression against the
humerus.
Signs: test for wrist and finger drop with elbow flexed and arm pronated;
sensory loss variable- the dorsal aspect of the root of the thumb (anatomical
snuff-box) is mostly reliably affected.
Lateral femoral cutaneous nerve compression
 Lateral femoral cutaneous nerve compression

Aetiology: entrapment usually occurs at inguinal ligament. Peak incidence is middle age.
Causes: Entrapment may be from intrapelvic/extra pelvic/mechanical causes. Intrapelvic causes: pregnancy,
abdominal tumours, uterine fibroids, diverticulitis/appendicitis/aortic aneurism. Extra pelvic causes: trauma to
region of ASIS (e.g. from seatbelt), tight garments, belts, girdles/stretch from obesity/ascites. Mechanical: pro-
longed sitting/standing/pelvic tilt from leg length discrepancy. DM.
Differentials: lumbar radiculopathies & discogenic/nerve root problems at L2 and L3.
Clinical: symptoms: anterior/lateral thigh burning/tingling/numbness ↑with standing/walking/hip
extension/lying prone. Symptoms usually unilateral and usually improve with sitting unless compressive forces
such as tight belts/garments remain. Exam: may be normal. Hyperesthasia over lateral thigh. Pain can be
produced by pressure medial to ASIS. + tinnel sign may be present over ASIS/inguinal ligament.
Diagnosis: injection of local anaesthetic near inguinal ligament/ASIS. Spontaneous recovery usually expected.
Electrodiagnostic testing. Nerve conduction studies. (response small & hard in obese pts) so needle
stimulation electrode needed- sensory response absent in 71% of pts with meralgia parasthetica and
prolonged in 24% of pts with this condition- electromyographic results are normal with pts with this condition.
Treatment: injection of local anaesthetic agents-steroid can prolong effects and reduce inflammation.
NSAIDs, antiseziues (neurotin), tricyclic antidepressants, tramadol, capsaicin cream & topical lidocaine.
Advise pt to prevent further irritation of nerve (avoid hip extension, prolonged standing, compressive
garments). Use of ICE and TENS unit may help. Surgical exploration may be required is all above fail
(transection of nerve/decompression with/without neurolysis- anatomical variations of nerve & neuromas
may lead to recurrence).
 Sciatic n erv e damage

Very common. Back pain tends to affect those between 30-60. est. 4.9m working days lost annually due to back pain.
Risk factors: Psych-social work related stress, genetics, smoking and obesity ↑ risk.
Red flags from history: recent violent trauma (e.g. strenuous weight-lifting). Age of onset <20 or 50> (new back pain). History
of: drug abuse, cancer, HIV, immunsupression, prolonged use of corticosteroids. Fever, chills, unexplained weight-loss. Recent
bacterial infection. Pain that is: worse when supine/in night. Thoracic. Constant & progressive. Non-mechanical without relief
from bed/postural modification. Unchanged despite treatment for 2-4wks. Accoampenied by severe morning stiffness. Severe
& leaves pt unable to walk/self-care. Accompanied by saddle anaesthesia/bladder/bowel problems.
Exam: exam of spine with pt standing & undressed. Inpsection/palpation/brief neuro exam/assessment of function. Detailed
neuro exam if confirm reg flags e.g. saddle anaesthisa. Passive straight leg raising to assist diagnosis of nerve pain. Red flags:
structucal deformity, severe/progressive neuro deficit in lower extremuities. Unexpected laxity of anal sphincter.
Perianal/perineal sensory loss. Major motor weakness. Cauda equine syndrome suspected if: bladder dysfunction/sphincter
disturbance/saddle anaesthisa/lower limb weakness/gait disturbance.
Differentials: primary malignancy (myeloma, pancreas, oestocarcoma). Secondary cancers from: breast, bronchus, prostate,
thyroid, kidney. Bone disoders: paget’s disease of bone, osteoporosis, spinal stenosis. Inflammatory disease: ankylosing
spondylitis, slowly in men <40, rigid back, aggravation with inactivity & relief by exercise. Psoriactic arthris/reiters
syndrome/arthritis. Infection: TB, HIV, renal tract infection. Causes outer spine: dissection aortic aneurism, posterior
dudodenial ulcer= if gastric ulcer presents first time over 40, exclude malignancy. Nephrolithiasis. Plelonephritis. Factors
suggesting malignancy: 50yr>, previois cancer, pain lasting 1m>, failure to improve with conservative therapy, elevated EST &
anemia.
Investigations: X-RAY, CT for stress fractures, MRI best for soft tissue/disc lesion. FBC, ESR, CRP, urine analysis if cancer
suspected. LFT’s- alkaline elevated in metastatic disease & paget’s disease of bone. PSA raised particularly in carcinoma of
prostate. Urinary hydroxyproline marked elevated in pagets disease of bone. Nephrolithiasis may produce red cells in urine. US,
endoscopy.
 Sciatica /g eneral back pa in mana gement:

Management of simple back-pain: DO NOT prescribe bed rest, advise pt to say active
as possible, regular pain relief, referral: consider physical treatments if not resuming
work/normal activities after 2wks, red flag.
Management chronic/psychosocial/yellow flags: induction for heavy
lifting/maintaining form, seating/posture in car/work (e.g. adjusting seat), fork lift
trucks/large goods vehicles may transmit vibrations all day. Discuss getting back to
work, alterations to workplace, gt positive attitude to pt & enthusiasm. Referral: red
flags, progressive/persistent neuro deficit, pain/disability remain problematic 2wks>.
Psychological therapies: CBT, relaxation therapies.
Complications: chronic back-pain, failure to diagnose CES, other sinister causes of
back-pain.
Prognosis: depends entirely on diagnosis. Simple back-pain will resolve but time is
invariable. For elderly, usually gets worse with yrs. Analgesia may help but most
importantly stay active.
Prevention: alterations to work, addressing physical and psycho-social issues.
 Common perineal nerve

Top mid pic shows foot drop for the left foot due to fibular nerve damage.
 Co mmon peron eal nerve

Damage to the pernoeal nerve leading to loss of movement/sensation in foot and leg.
Perinoeal nerve is a branch of sciatic nerve supplying movement & sensation to lower leg, foot and toes.
Common perinoeal nerve damage is a type of Peripheral neuropathy (damages to nerve outside brain/spine).
Condition effects people of all ages. (mononeuropathy= dysfunction of single nerves- damage to one area).
Causes: trauma to knee. Fracture of fibula. Use of tight plaster cast of lower leg. Crossing legs
regularly/wearing high boots. Pressure to knee during sleep/coma. Injury during surgery/placed in awkward
position during anaesthesia. More common in people with: very thin, DM, polyarteritis nodosa, exposed to
toxins.
Symptoms: decrease sensation/numbness/tingling on top of foot in outer/lower leg. Foot that drops.
Slapping gait. Toes drag while walking. Walking problems. Weakness in ankles/feet.
Exams/tests: loss of muscle control in lower leg/feet, atrophy of foot/foreleg muscles. Difficulty lifting up
foot/toes & making toe-out movements. EMG. Nerve conduction studies. MRI. Nerve US.
Treatment: padding knee. Corticosteroids injected to reduce swelling/pressure on nerve. Surgery if:
refractory disorder, problems with movement, evidence of nerve axons damage , remove tumours. Surgery
can release pressure. Painkillers/NSAID’s. physical therapy exercises. Orthopaedic devices e.g. braces.
Prognosis: decrease ability to walk, permanent decrease in sensation in legs/foot- also perm
weakness/paralysis.
Prevention: avoid putting long-term pressure to back/side of knee- treat injuries right away. If a
cast/splint/dressing/or other pressure on lower leg causes a tight feeling/numbness, call provider right away.
 Pancreatitis- acute

Symptoms: Gradual or sudden severe epigastric or central abdominal pain (radiates to back, sitting forward
relieves) vomiting prominent
Signs: Tachycardia, jaundice, shock, rigid abdomen, tenderness, preumbillical bruising
Tests: raised serum amylase (>1000u/mL), cholecystitis, mesenteric infarction. ABG to monitor O2 & acid-base
status. Erect CXR to exclude other causes. CT to assess severity.
Management: nil by mouth- may need NG tube. Set up IVI with lots of saline. Set up urinary catheter.
Analgesia: pethidine IM. Hourly: pulse, O2, urine, daily: FBC,U&E,CA2+, glucose, amylase, ABG.
If worsening: ITU, O2 if PaO2 low. Antibiotics may help.
Ulcerative colitis
- note mucosa lesions of inflamed mucosa
Ulcerative colitis
 ulcerative colitis

UC is a relapsing & remitting inflammatory disorder of the colonic mucosa. It may affect just the rectum (proctitis, as in ~50%)
or extend proximally to involve part of the colon (left-sided colitis~30%) or the entire colon (pancolitis, in~20%). It ‘never’
spreads proximally to the ileocaecal valve (except for backwash ileitis).
Cause: unknown, maybe genetic.
Pathology: hyperaemic/haemorrhagic granular colonic mucosa +/- pseudopolyps formed by inflammation. Punctate ulcers may
extend deep into lamina propria- inflammation is normally not transmural.
Histology:
Incidence: mostly present in 15-30yo’s. UC is 3x as common in non-smokers (opp true for Crohns)- symptoms may relapse on
stopping smoking.
Symptoms: gradual onset of diarrhoea (+/- blood & mucus). Crampy abdominal discomfort is common; bowel frequency is
related to severity of disease. Systemic symptoms are common during attacks e.g. fever, malaise, anorexia, weight ↓. Urgency
& tenesmus occur with rectal disease.
Signs: may be none. In acute, severe UC there may be fever, tachycardia & tender distended abdomen. Extraintestinal signs:
clubbing, aphthous, oral ulcers; erythema nodosum, pyoderma gangrenosum, conjunctivitis, episcleritis, iritis, large joint
arthritis, sacroiliitis, ankylosing spondylitis, fatty liver, PSC, cholangio-carcinoma, nutritional deficits, amyloidosis.
Tests: Blood: FBC, ESR, CRP, U&E, LFT, & blood cultures. Stool MC+S and CDT to exclude infections. AXR: no faecal shadows,
mucosal thickening/islands, colonic dilatation. Erect CXR: perforation. Sigmoidoscopy: inflamed, friable mucosa. Rectal biopsy:
inflammatory infiltrate, goblet cell depletion, glandular distortion, mucosal ulcers, crypt abscesses. Barium enema: never do
barium enema during a severe acute attack or as a diagnostic test. Colonoscopy shows disease extent & allows biopsy.
Complications: perforation & bleeding are 2 serious dangers, also: toxic dilatation of colon, venous thrombosis: give
prophylaxis to all inpatients, colonic cancer: risk ~15% with pancolitis for 20yrs; surveillance colonscopy may be used, but
proving this saves lives has been difficult.
 ulcerative colitis continued…

Inducing remission: Mild UC: if <4 motions/d & the pt is well, give prednisolone or Asacol. For mild distal disease use 2x daily steroid
foams PR. If symptoms improve, ↓steroids gradually. If no improvement after 2w, treat as moderate UC.
Moderate UC: if 4-6 motions/d, but otherwise well, give oral prednisolone, slowly decreasing dose + a 5-aminosalycilic acid + 2x daily
steroid enemas. If improving, ↓steroids gradually. If no improvement after 2w, treat as severe UC.
Severe UC: If systemically unwell & passing >6 motions/3, admit for: nill by mouth & IV maintenance hydration (saline + dextrose saline),
hydrocortisone, rectal steroids e.g. hydrocortisone in saline, monitor T, pulse and BP & record stool frequency/character on a stool chart.
2x daily exam: document distension, bowel sounds & tenderness. Daily FBC, ESR, CRP, U&E, +/e AXR. Consider need for blood transfusion
(if Hb <10g/dL) Parenteral nutrition is only very rarely required (e.g. only if severely malnourished). If improving in 5d, transfer to
prednisolone PO with a 5-ASA (e.g. sulfasalazine). If on a day 3 CRP >45 or stool frequency >6, consider ciclosporin/infliximab/surgery.
Topical therapies: proctitis may respond to suppositories (prednisolone). Topical 5-ASA’s work better than topical steroids. Procro-
sigmoiditis may respond to foams PR; disposable applicators aid accurate delivery. Retention enemas may be needed in left-sided colitis.
Surgery ~20% will require at some stage. Procedures: proctocolectomy + terminal ileostomy, colectomy with later ileo-anal pouch. Surgical
mortality: 2-7% ↑ to 50% if perforation. Pouchitis can be successfully treated with antibiotics e.g. metronidazole + ciprofloxacin for 2w &
immunosuppressant's.
Novel therapies: short course of ciclosporin may help obtain remission quickly in pts with steroids-refactory UC, although it is markedly
nephrotoxic & not suitable for long courses (monitor levels, do U&E, LFT, BP often- stop if raised, get expert help.) short-term response to
ciclosporin is generally good but long-term remission is disappointing. Infliximab may be effective as rescue therapy in UC, although
evidence is scarce.
Maintaining remission all 5-ASAs ↓relapse rate from 80 to 20% at 1yr-examples are sulfasalazine, mesalazine & olsalazine. Maintenance
continues for life. Sulfasalazine, SE’s relate to sulfapyridine intolerance (headache, nausea, anorexia, malaise). Other SE’s: T ↑, rash,
haemolysis (monitor FBC), hepatitis, pancreatitis, paradoxical worsening of colitis & reversible oligospemia. Newer 5-ASAs (e.g. mesalazine
or olasalzine) are just as effective at maintaining remission, have fewer SEs but more expensive. Indicated in sulfasalazine intolerance &
young men in whom fertility is a concern (less effect on sperm). Azathioprine indicated as a steroid sparing drug in those with steroid side
effects or those who relapse quickly if steroids are reduced. Treat for several months, monitor FBC every 4-6w.
IBS
 IBS

IBS denotes a mixed group of abdominal symptoms for which no organic cause
can be found. Most are probably due to disorders of intestinal motility or
enhanced visceral perception. Prevalence: 10-20%; age at onset: <40yrs: female
to male= 2:1.
Diagnosis: only diagnose IBS if abdominal pain, is either relieved by
defecation/associated with altered stool form or bowel frequency & there are 2>
of: urgency; incomplete defecation; abdominal bloating/distension; mucous PR;
worsening of symptoms after food. Other symptoms: nausea, bladder,
symptoms, backache. Symptoms are chronic (6>M) & exacerbated by stress,
menstruation or gastroenteritis (typical post-infection IBS). Signs: exam is often
normal, but general abdominal tenderness is common. Insufflation of air during
sigmoidoscopy (not usually needed) may produce pain. Markers suggesting
disease other than IBS: Age 40> (esp male), history <6M, anorexia, ↓weight,
waking at night with pain/diarrhoea, mouth ulcers, abdominal CRP, ESR, Hb,
coeliac serology. Investigate PR bleeding urgently.
 IBS continued…

Make +ve diagnosis but also ‘exclude’ other diagnoses, so: if history is classic, FBC, ESR, CRP, LFT & coeliac serology is sufficient. If
60>yrs or any marker or organic disease (Weight ↓, blood PR, ↑T): colonoscopy. Have a low threshold for referring if family history
of ovarian/bowel cancer. If diarrhoea is prominent, do: LFT, stool culture; B12/folate, antiendomysial antibodies, TSH, consider
referral +/- barium follow-through (if symptoms suggest small bowel disease) +/- rectal biopsy.
Further investigation should be guided by symptoms & include: upper GI endoscopy (dyspepsia, reflux) or small bowel radiology
(crohn’s). Duodenal biopsy (coeliac disease) e.g. if antiendomysial antibodies +ve. Giardia tests (often triggers IBS, anti-parasitic px
may not help). ERCP (e.g. chronic pancreatitis) or MRCP if active pancreatitis.
Refer if: 1) diagnosis unsure 2) changing symptoms in ‘known IBS’ 3) to surgeon if rectal mucosal prolapse 4) to dietician if food
intolerance 5) to counsellor if marked stress or depression is 6) to gynaecologist if cyclical pain,
dyspareunia/dysmenorrhoea=endometriosis often mimics IBS 7) dermatologist if xo-existing atopy (IBS is 3x more common in
atopy). 8) to yourself/pain clinic if overlapping chronic pain syndromes (fibromyalgia, chronic fatigue, chronic pelvic pain) or
detrusor problems.
Food intolerance: exclusion diets may be tried (difficult, may lead to obsessions) try limiting cereals high in bran, & whole grains
such as brown rice) in a few, fructose intolerance is part of the problem. Drink plenty but limit tea/coffee/alcohol/fizzy drinks).
Probiotics may help: once-daily bacillus coagulans GBI-30, B.infantis, E.coli DSM17252 & L.acidophilus-SDC can help pain & bloating.
Constipation: ↑fibre intake slowly (can paradoxically worsen flatulence/bloating; avoid insoluble fibre, such as bran). Fibogel
(ispahgula) or celevac (methylcelluose) have non-fermentable fibre & are better than lactulose which ferments (↑gas production is
hard to distinguish from bloating). Diarrhoea: try avoiding sorbitol (artificial sweetener); try a bulking agent +/- loperamide after
each loose stool, SE: colic, nausea, dizziness, constipation, bloating, ileus. Bismuth, SE: dark stools.
Colic/bloating: antispasmodics: mebeverine, alverine citrate, dicycloverine. Dyspeptic symptoms: may respond to
metoclopramide or antacids.
Psychological therapy: emphazise +ve aspects & prognosis: in 50% symptoms go/improve after 1yr; <5% worsen. Symptoms are still
troublesome in the rest at 5yrs. Tricyclics are often helpful e.g. amitriptyline at night, SE: constipation, dry mouth etc. CBT & gut-
focus hypnotherapy all have roles. Explains that all forms of stress perpetuate IBS.
C el iac di s ea s e
 Coeliac disease

Suspect in those with diarrhoea + weight loss or anaemia. This is a T-cell mediated autoimmune
disease of small bowel in which prolamin (alcohol soluble proteins in wheat, barley, rye +/- oats)
intolerance causes villous atrophy & malabsorption. Associations: HLA DQ2 in 95%; the rest are
DQ8; autoimmune disease; dermatitis herpetiformis. Prevalence: 1 in 300-1500 (more common in
Irish). Occurs at any age (peaks in infancy & 50-60yrs). There is 10% prevalence in 1 st degree
relatives & in 30% relative risk for siblings.
Presentation: steatorrhoea (fatty stools); diarrhoea; abdominal pain; bloating; nausea + vomiting;
apthous ulcers, angular stomatitis; weight ↓; fatigue; weakness; iron-deficiency anaemia;
osteomalacia; failure to thrive (children). 1/3 are asymptomatic.
Diagnosis: antibodies: alpha-gliadin, transglutaminase & anti-endomysial- an IgA antibody, 95%
specific unless pt is IgA deficient. Duodenal biopsy done at endoscopy: subtotal villous atrophy,
↑intra-epithelial WBCs + crypt hyperplasia, reversing on gluten-free diet. Exclude coeliac disease in
any pt with IBS.
Treatment: lifelong gluten-free diet- rice, maize, soya, potatoes, oats (<50g/d), & sugar are ok.
Gluten-free biscuits, flour, bread & pasta are prescribable. Verify diet by endomysial antibody tests.
Complications Anaemia; 2 lactose-intolerance; GI T-cell lymphoma (rare; suspect if refractory
symptoms or ↓weight); ↑risk of malignancy (gastric, oesophageal, bladder, breast, brain);
myopathies, neuropathies; hyposplenism; osteoporosis.
Hiatus hernia

Sliding hiatus hernia

 Hiatus hernia

Sliding hiatus hernia= (80%) is where gastro-oesphageal junction slides up into chest.
Acid reflux often happens as lower oesphageal sphincter becomes less competent
in many cases.
Rolling hiatus hernia (20%) is where the gastro-oesphageal junction remains in the
abdomen but a bulge of stomach herniates up into chest alongside oesophagus. As
gastro-oesphageal junction remains intact, gross acid reflux is uncommon.
Clinical features: common: 30% pts 50yrs> esp obese women. 50% have
symptomatic gastro-oesphageal reflux.
Imaging barium swallow is best diagnostic test; upper GI endoscopy visualises the
mucosa (oesphagitis?) but cannot reliably exclude a hiatus hernia.
Treatment: lose weight. Treat reflux symptoms. Surgery indications: intractable
symptoms despite aggressive medical therapy, complications. It is advised to repair
rolling hiatus hernia prophylactically (even if asymptomatic) as it may strangulate,
which needs prompt surgical repair (which has high morbidity and mortality rate).
 Travellers diarrhoea/gastroenteritis

Contaminated food & water common sources of pathogens but often no specific cause
found. Ask about details of food/water taken/cooking method/time until onset of
symptoms/whether fellow diners were affected. Ask about swimming, canoeing etc.
Food-poisoning is a notifiable disease in UK.
Tests: stool microscopy/culture if from abroad, an institution, or in day care, or an
outbreak is suspected. In these circumstances culture of the food source may help.
Prevention: hygeine; if abroad, avoid unboiled/unbottled water, ice cubes, salads, and
peel own fruit. Eat only freshly prepared hot food. House-hold water treatment & safe
storage technologies can ↑water quality and ↓rates of diarrhoea e.g. Chlorine/solar
disinfection, and ceramic or biosand filtration.
Management: usually symptomatic. Maintain oral fluid intake (+/- oral rehydration
sachets). For severe symptoms (but no dysentery), give anti-emetics e.g. Pro-
chloroperazine + antidiarrhoeals (codeine phosphate or loperamide). Antibiotics are
only indicates if systematically unwell, immunocomp/elderly; resistance is common.
Cholera: tetracycline reduces transmission. Salmonella: ciprofloxacin (antibiotic therapy
may ↑no. Of chronic carriers). Shigella & campylobacter: ciprofloxcin.
 Crohn’s disease

Crohns disease is a chronic inflammatory GI disease characterized by transmural granulomatous inflammation. It may affect any part of
gut from mouth to anus but favours terminal ileum(50%) & proximal colon. Unlike UC, there is unaffected bowel between areas of
active disease (skip lesions). Cause: unknown. Mutations of ND/CARD gene ↑risk. Prevalence: 50-100/100k. Associations: altered cell-
mediated immunity. Smoking ↑risk x3-4 & NASIDs may exacerbate disease.
Symptoms: diarrhoea, abdominal pain & weight loss are common (failure to thrive in children), fever, malaise, anorexia occur with active
disease.
Signs: aphthous ulcerations; abdominal tenderness; right iliac fossa mass; perianal abscesses/fistulae/skin tags; anal/rectal strictures.
Extraintestinal signs: clubbing, erythema nodosum, pyoderma gangrenosum, conjunctivitis, episcleritis, iritis, large joint arthritis,
seronegative spondyloarthropathy, fatty liver, PSC, cholangiocarcinoma, renal stones, osteomalacia, malnutrition, amyloidosis.
Complications small bowel obstruction; toxic dilatation; abscess formation (abdominal/pelvic or ischio-rectal); fistulae (present in 10%),
e.g. Colovesical (bladder), colovaginal, perianal, enterocutaneous; perforation; rectal haemorrhage; colonic carcinoma.
Tests: Blood: FBC, ESR, CRP, U&E, LFT, blood culture. Serum iron B12 & RC folate if anaemia. Markers of activity: Hb ↓; ↑ESR; ↑CRP;
↑WCC; ↓albumin. Stool MC+S and CDT to exclude infectious diarrhoea. Do sigmoidoscopy + rectal biopsy if mucosa looks normal.
Small bowel enema detects ileal disease. Capsule endoscopy. Barium enema (rarely used) may show cobblestoning, ‘rose thorn’ ulcers,
& colon strictures with rectal sparing. Colonoscopy is preferred to barium enema to assess disease extent. MRI can assess pelvic disease
& fistulae. Small bowel MRI can assess disease activity & show site of strictures.
Management: severity is harder to assess than in UC but albumin ↓, ↑Temp, ↑pulse, ESR ↑, CRP ↑, WCC ↑ reflect severity & merit
admission. Mild attacks: pts symptomatic but systematically well. Prednisolone is given. If symptoms resolve decrease prednisolone
and stop when parameters=normal. Severe attacks: admit for IV steroids & hydration. Then give: hydrocortisone. Treat rectal disease=
give steroids. Metronidazole helps- SE: alcohol intolerance; irreversible neuropathy. Monitor T, pulse, BP & record stool
frequency/character on stool chart. Physical exam daily plus FBC, ESR, CRP, U&E, & plain AXR daily. Consider need for blood transfusion
& parenteral nutrition. If improving after 5d, transfer onto oral prednisolone. If no response during IV therapy, consider CT abdomen to
exclude collections & seek surgical advice. Perianal disease occurs in about 50%. MRI & exam under anaesthetic are important part of
assessment. Treatment includes oral antibiotics, immunosupressants +/- infliximab & local surgery +/- seton insertion.
C roh ns di s ea s e

eFigure 15–93. Crohn disease of the colon. This barium enema

illustrates a rectum and sigmoid colon that appear normal. The
descending colon is narrowed and has an irregular contour with
areas of ulceration. In the region of the splenic flexure and distal
transverse colon, the caliber of the colon returns to normal. In the
midtransverse colon, there is a second area of involvement, with
ulcerations, abrupt narrowing, and irregularity consistent with a
thickened colon wall. The right side of the colon appears normal, an
unusual phenomenon in Crohns disease of the colon. Reflux of
barium is seen into multiple segments of the small bowel. These
appear normal. The colonic abnormalities seen here are classic for
Crohns disease. (Courtesy of H Goldberg.) for pic on left
 Crohn’s diease

Typical granulomas in all biopsies (circular things)

 Peptic ulcer disease (PUD)

Bottom L is duodenal ulcer and R is stomach ulcer.

 Peptic ulcer disease

Symptoms: usually non specific: epigastric pain e.g. Related to hunger, eating specific
foods, or time of day; may be associated with bloating +/- fullness after meals;
heartburn (retrosternal pain with demonstrable acid reflux). Alarm symptoms:
Anaemia (iron defiency); loss of weight; anorexia; recent onset of progressive
symptoms; melaena or haematemesis; swallowing difficulty. Signs: tender epigastrium
(non specific). Any abdominal mass; supraclavicular nodes +/- hepatomegaly?
Management: lifestyle: avoid food that worsens symptoms; stop smoking (slows
healing in GU & ↑relapse rates in DU). H.pylori eradication: triple therapy is 80-85%
effective at eradication. Drugs to reduce acid: PPIs are most effective e.g.
Lansoprazole. H2RAs may have a place for individual responders e.g. Ranitidine.
NASID-associated ulcers: stop NASID if possible. PPIs are most effective drugs for
treatment & prevention of GI ulcers & bleeding in pts on antiplatelet therapy.
Misoprostol has ↑side effects & sucralfate & H2 blockers are not adequately effective.
If symptoms persist, re-endoscope, recheck for H.pylori & reconsider the differential
diagnosis. Surgery.
Complications: bleeding, perforation, malignancy, gastric outflow ↓
Liver failure
 Liver failure

Causes: toxins- chronic alcohol abuse; paracetamol poisoning (occurs at lower level than
expected in alcohol abusers); drugs; poison by various substances such as
mushrooms/chemicals containing organic solvents; herbal preparations; Reyes syndrome.
Infections; viral hepatitis; adenovirus, Epstein-Barr virus, cytomegalovirus and viral hemorrhagic
fevers. Neoplastic: hepatocellular/metastatic carcinoma. Metabolic: Wilsons disease/others e.g.
alpha-1-antitrypsin deficiency, fructose intolerance, galactosaemia &tyrosinaemia. Vascular:
ischemia/veno-occlusive disease. Budd-chiari syndrome. Others: autoimmune, unknown etc.
History: ask about: date of onset of jaundice & encephalopathy. Alcohol. Meds inc prescribed and
illegal. Family history. Exposure risk factors for viral hepatitis (travel, transfusions, sexual
contacts, occupation, body piercing. Toxin ingestion (e.g. Mushrooms) PMH.
Exam: mental state. Jaundice. Hyperdynamic circulation with multiple organ failure may mimic
septic shock. Abdominal distension and abdominal masses, including: Possible massive ascites
and anasarca due to fluid redistribution and hypoalbuminaemia, a dehydrated patient may not
show much ascites, hepatomegaly and splenomegaly but not invariably. Ceberal oedema with
↑ICP may produce papilloedema, hypertension & bradycardia. Liver palms are red & an hepatic
flap also called asterixis may be present= hyperextend fingers & wrist, gently pushing back &
slow clonic movement is liver flap.
Differentials:
 Jaundice

Refers to yellow pigmentation of skin, sclerae and mucosae due to ↑plasma bilirubin (visible at >35umol/L- not
easy to spot when mild). Its classified by site of problem (pre-hepatic, hepatocellular or cholestatic/obstructive)
or by type of circulating bilirubin (conjugated/unconjugated). Kernicterus is seen in infants with unconjugated
hyperbilirubinaemia and involves deposition of unbound bilirubin in basal ganglia which can cause opisthotonus.
Unconjugated hyperbilirubinaemia: as unconjugated bilirubin is water insoluble, it does not enter urine,
resulting in unconjugated (acholuric) hyperbilirubinaemia. Overproduction: haemolysis; ineffective
erythropoiesis. Impaired hepatic uptake: drugs (contrast agents, rifampicin), congestive cardiac failure. Impaired
conjugation: glucoronyl transferase deficiency, physiological neonatal jaundice: caused by combo of above
(bilirubin production ↑due to short-life spans of RBCs, and bilirubin conjugation is not completely developed.
Conjugated hyperbilirubinaemia: hepatocellular dysfunction: hepatocyte damage with some cholestasis,
causes: viruses: hepatitis, EBV, drugs, alcohol hepatitis; cirrhosisl liver metastases/abscess; haemochromatosis;
autoimmune hepatitis septicaemia; leptospirosis, alpha1- antitrypsin deficiency; wilsons disease; failure to
excrete conjugated bilirubin (dubin Johnson & rotor syndromes), right heart failure; toxins e.g. carbon
tetrachloride; fungi. Impaired hepatic excretion: primary biliary cirrhosis, primary scelerosing cholangitis,
extrinsic compression of bile duct, drug-induced cholestasis, common bile duct gall-stones; pancreatitic cancer,
lymph nodes at porta hepatitis, drugs for cholangiocarcinoma, choledochal cyst, biliary atresia, Mirrizi’s
syndrome (obstructive jaundice from common bile duct compression by a gallstone impacted in cystic duct often
associated with cholangitis.) as conjugated bilirubin is water soluble it is excreted in urine making it dark. Less
conjugated bilirubin enters the gut and faeces become pale. When severe, it is associated with an intractable
pruritus which is best treated by relief of obstruction.
 Jaundice carried on…

Clinical features: ask about blood transfusions, IV drug use, body piercings,
tattoos, sexual activity, travel abroad, jaundiced contacts, family history. Alcohol
intake, all meds. Exam: for signs of chronic liver disease, hepatic encephalopathy,
lymphadenopathy, hepatoamegaly, splenomegaly, ascites and a palpable gall
bladder (which in conjuction with painless jaundice suggests cause other than
gallstones- Courvoisier’s ‘law’). Pale stools with dark urine= cholestatic jaundice.
Tests: same tests for suspected liver disease + urine: bilirubin is absent in pre-
hepatic causes hence ‘acholuric’ jaundice; urobilinogen is absent in obstructive
jaundice. Haematology: FBC, clotting, blood film, reticulocyte count, coombs
test. Biochem: U&E, LFT. US: are bile ducts dilated >6mm. Are there gallstones,
hepatic metastases or a pancreatitic mass? ERCP if bile ducts are dilated and LFT
not improving. MRCP or endoscopic US if conventional US shows gallstones but
no definite common bile duct stones. Perform liver biopsy if bile ducts are
normal. Consider abdominal CT/MRI if abdominal malignancy is suspected
clinically.
 Diarrhoea

It means increased stool water which ↑stool frequency. If stools fat content ↑its called steatorrhoea (pale,
malodours stool difficult to flush away). Clinical features: acute/chronic? If acute suspect gastroenteritis. Ask
about travel, change in diet and contact history. Chronic diarrhoea alternating with constipation suggests IB.
anorexia, weight↓, nocturnal diarrhoea & anaemia suggest organic cause.
Bloody diarrhoea: campylobacter, shigella, salmonella, E.coli, amoebiasis, UC, Crohns disease, colorectal cancer,
colonic polyps, pseudomembranous colitis, ischaemic colitis. Mucus occurs in IBS, colorectal cancer and polyps.
Pus suggests IBD, diverticulosis, or a fistula/abscess. Large bowl symptoms: water stool +/- blood/mucus; pelvic
pain relieved by defection; tenesmus; urgency. Small bowel symptoms: pre-umbilical pain not relieved by
defecation; water stool/steathorrea. Non GI causes: antibiotics; PPI’s, cimetidine; propranolol, cytotoxics; NSAIDs;
digoxcin; alcohol; autonomic neuropathy; Addisons disease; carcinoid syndrome. Exam: look for weight↓,
clubbing, anaemia, oral ulcers, rashes and abdominal scars. Assess severity of dehydration (dry mucous
membranes, ↓skin turgor and cap refill >2s). Feel for enlarged thyroid/abdominal mass. Do rectal exams for
mass’s (e.g. rectal CA) or impacted faeces (overflow diarrhoea). Test for faecal occult blood. Tests: Bloods: FBC
(iron deficiency, ↑MCV in coeliac disease, ↑alcohol use, ileal Crohn’s (as B12 absorption low); U&E (K+ ↓), ESR
↑(cancer, IBD), CRP ↑(infection, IBD). TSH ↓(thyrotoxicosis), coeliac serology (duodenal biopsy). Stool: test for
pathogens & C.diff toxin (pseudomembranous colitis). Faecal fat excretion or 13C-hiolein (highly labelled triolein)
breath test (nicer and reliable) of symptoms of chronic pancreatitis, malabsorption, or steatorrhoea. Rigid
sigmoidoscopy: with biopsy of normal and abnormal looking mucosa~15% of pts with Crohn’s have
macroscopically normal mucosa. Colonoscopy/Ba enema: (malignancy? Colitis?) = avoid during severe episode. If
normal, consider small bowel radiology (e.g. Crohn’s) +/- ERCP (chronic pancreatitis).
 Diarrhoea continued…

Management: treat causes. Food handlers must not work until stool samples –
ve. If an outbreak, wards may need to be closed. Oral rehydration is better than
IV rehydration, if impossible, give saline and K+ IVI= if rehydrated and bloody
diarrhoea for >2wks, IV fluids may well be needed. Codeine
phosphate/loperamide after each loose stool reduce stool frequency. Avoid
antibiotics except in infective diarrhoea causing systemic illness because of risk
of developing resistance.
 Cirrhosis

Implies irreversible liver damage. Histologically there is loss of normal hepatic architecture with bridging fibrosis
and nodular regeneration. Causes: most often chronic alcohol abuse, HBC and HVC infection. Signs: may be none
(just ↑LFT), or decompensated end-stage liver disease. Chronic liver disease: leuconychia: white nails with
lunulae undemarcated from hypoalbuminaemia; terry nails- white proximally but distall 1/3 reddened by
telangiectasis; clubbing; palmar erythema; hyperdynamic circulation; dupuytrens contracture; spider naevi;
xanthelasma; gynaecomastia, atrophic testes, loss of body hair, paratoid enlargement, hepatomegaly or small
liver in late disease. Complications: hepatic failure: coagulopathy (↓factors II, VII, IX & X causes ↑INR);
encephalopathy- ie liver flap (asterixis) + confusion/coma; hypoalbuminaemia (oedema, leuconychia); sepsis,
spontaneous bacterial peritonitis (SBP), hypoglycaemia. Portal hypertension: ascites, splenomegaly, Porto-
systemic shunt including oesophageal varices (+/- life-threatening upper GI bleed) and caput medusa (enlarged
superficial umbilical veins). HCC: ↑risk. Tests: blood: LFT, ↑/ ↓, or ↑bilirubin, ↑AST, ↑ALT, ↑alk phos and
↑gamma GT. Later, with loss of synthetic function, look for ↓albumin +/- ↑PT/INR. ↓wcc and ↓platelets
indicate hypersplenism. Find cause: ferritin, iron/total iron-binding capacity; hepatitis serology;
immunoglobulins; autoantibodies; alpha-fetoprotein; caeruloplasmin in pts <40yo, alpha1 antitrypsin. Liver US +
duplex may show a small liver or hepatomegaly, splenomegaly, focal liver lesion(s), hepatic vein thrombus,
reversed flow in portal vein or ascites. MRI: caudate lobe size ↑, smaller islands of regeneration nodules, and the
presence of right posterior hepatic notch more frequent in alcoholic than virus cirrhosis. Ascites tap should be
performed & fluid sent for urgent MC+S- neutrophils >250/mm3 indicates spontaneous bacterial peritonitis. Liver
biopsy confirms clinical diagnosis.
 Cirrhosis management co ntinued …

Management: general: good nutrition is vital. Alcohol abstinence, baclofen helps

cravings and no CI in cirrhosis unlike naltrexone (avoid in hepatorenal syndrome). Avoid
NSAIDs, sedatives and opiates. Colestyramine helps pruritus. Consider US +/- alpha-
fetoprotein every 3-6m to screen for HCC. Specific: interferon- alpha improves LFT &
may slow development to HCC in HCV-induced cirrhosis. High-dose ursdeoxycholic acid
in PBC may normalise LFT but may have no effect on disease progression. Penicillamine
for wilsons disease. Ascites: bedrest, fluid restriction, low salt diet. Give spironolactone
which counters de-ranged renin angiotensin aldosterone axis. Chart daily weight and
aim for weight loss, if response poor add furosemide, do U&E frequently (watch Na+).
Therapeutic paracentesis with concomitant albumin infusion may be tried.
Spontaneous bacterial peritonitis: must be considered in any pts with ascites who
deteriorates suddenly (may be asymptomatic). Common organisms: E.coli, klebsiella
and streps. Px: cefotaxime/tazocin. Give Px for high-risk pts or those who have had a
previous episode e.g. norfloxacin. Prognosis: overall 5yr survival is ~50%. Poor
prognostic indicators: encephalopathy; serum Na+ <110mmol/L; serum albumin
<25g/L; ↑INR. Liver transplant: only definite treatment for cirrhosis, increased 5yr
survival from ~20% in end stage to ~70%.
 Cirrhosis

Hepatomegaly
Portal HTN
 Portal HTN

Oesophageal varices indicate portal HTN

 Po rta l hy per ten s io n

Portal HTN refers to abnormal high pressure in hepatic portal vein. Clinically significant portal HTN is defined as hepatic venous
pressure gradient of 10mmhg>
Aetiology: causes: prehepatic: Congenital atresia/stenosis, portal vein thrombosis (idiopathic, umbilical, & portal sepsis,
malignancy, hypercoaguable states, pancreatitis). Splenic vein thrombosis, extrinsic compression e.g. tumours. Hepatic: Cirrhosis,
Chronic hepatitis, schistosomiasis, Myeloproliferative disease, idiopathic portal HTN, granulomata- e.g. sarcoid, nodular (nodular
regenerative hyperplasia, partial nodular transformation), toxins (arsenic, vinyl chloride), fibro-polycystic disease (including
congenital hepatic fibrosis). Post-hepatic (blockage of hepatic veins/venules). Budd-Chiari syndrome (hepatic vein obstruction),
constrictive pericarditis, right HF, veno-occlusive disease of the smaller hepatic veins/venules (due to ingestion of pyrrolizidine
alkaloids, antileukamic drugs, radiation). Sclerosing hyaline necrosis. Other causes: ↑ hepatic flow: ↑splenic blood flow- e.g.
massive splenomegaly, hepatoportal arteriovenous fistula, idiopathic (a diagnosis of exclusion). L-sided (sinistral) portal HTN:
rare, confined to left side of portal system. May present as bleeding from varices. Usually it is due to pathology involving splenic
vein or the pancreas. Pathophysiology: portal HTN develops due to: ↑vascular resistance to portal venous system from various
mechanical causes & also an active process in which liver damage activates stellate cells & myofibroblasts, contributing to the
abnormal blood flow patterns; ↑blood flow in portal veins- from splanchic arteriolar vasodilation, caused by an excessive release
of endogenous vasodilators. ↑portal pressure opens up venous collaterals connecting the portal & systemic venous systems,
these occur in various sites: Gastro-oesophageal junction- producing varices which are superficial & easily bleed; anterior ab wall:
via umbilical vein- visible as caput medusa radiating from the umbilicus; may also occur when adhesions exist between ab viscera
& parietal peritoneum, or at sites of stomas or previous surgery; anorectal junction- rarely cause bleeding. Other patterns of
blood flow: if individual tributaries of portal vein are thrombosed, this causes local venous HTN with splenic vein block,
oesophageal & gastric varices may result; In Budd-Chiari syndrome (hepatic vein occlusion), collaterals open up within liver; blood
tends to be diverted through the caudate lobe whose short hepatic veins drain directly into IVC. Portosystemic venous
anastomoses can cause encephalopathy, possibly due to various ‘toxins’ bypassing the liver’s ‘detox’ process. Circulatory
disturbances: portal HTN & cirrhosis produce a hyperdynamic circulation, with splanchnic (visceral organs) vasodilatation,
↑cardiac output, arterial hypotension & hypervolemia; there is salt & water retention, ascites & hyponatremia.
 Portal HTN continued…

Presentation: History: History of jaundice, alcohol consumption, blood transfusion, esp abroad; lifestyles that
predispose to hep B/C. Family Hx e.g. wilsons disease, or hereditary haemochromatosis. For complications of portal
HTN: haematemesis or melena- suggests bleeding varices; lethargy, irritiability & changes in sleep pattern- suggests
encephalopathy; ↑ ab girth, weight gain suggests ascites; ab pain & fever- suggests spontaneous bacterial
peritonitis; pulmonary involvement is common in pts with portal HTN. Exam: signs of portal HTN: dilated veins in
the anterior ab wall & caput medusa (tortuous collaterals around umbilicus) a venous hum, loudest during
inspiration, is sometimes heard over large upper collaterals; splenomegaly; ascites. Signs of LF: jaundice, spider
naevi, palmar erythema; confusion, liver flap & fetor hepaticus are signs of encephalopathy; signs of hyperdynamic
circulation: bounding pulse, low BP, warm peripheries; enlarged/small liver; Gynaecomastia & testicular atrophy.
Investigations: Blood tests: LFTs, U&E, glucose, FBC, clotting screen; tests for liver disease if cause unknown: e.g.
ferritin (for haemochromatosis), hepatitis serology, autoantibodies, alpha-1 antitrypsin (for alpha-1-antitrypsin
deficiency), ceruloplasmin (for Wilson’s disease). Scans: Ab US- for liver & spleen size, ascites, portal blood flow &
thrombosis of portal/splenic veins; doppler US- can show direction of flow in blood vessels; CT scan, esp spiral CT
may show portal vasculature- can be useful if US inconclusive; MRI scan gives similar info to CT; elasticity
measurement (Fibroscan)- a new technique based on the velocity of an elastic wave via an intercostally placed
transmitter. Results correlate with liver stiffness & so with fibrosis. Endoscopy for oesophageal varices- essential for
those with suspected portal HTN, varices indicate portal HTN but their absence doesn’t exclude it. Liver biopsy- if
indicated may help diagnose underlying cause. Vascular imaging: site of portal venous block can be demonstrated
by examining venous phase of a celiac/super mesenteric arteriogram by splenic portography following injection of
dye into splenic pulp or by retrograde portography via a hepatic vein; hepatic venography is helpful when hepatic
vein block or idiopathic portal HTN is suspected.
 Portal HTN continued…

Management: difficult to treat effectively but treating underlining cause (where possible) & liver transplant (if indicated &
possible). Portal venous pressure can be reduced by B-blockers +/- nitrates & by using shunt procedures to create an
anastomosis between portal & hepatic veins. Conservative management includes salt restriction & diuretics. Some pulmonary
vasoactive drugs (e.g. epoprostenol) have become routine in the treatment of pts with idiopathic pulmonary HTN. Bleeding from
oesophageal is a life threatening complication of portal HTN. Primary prevention of bleeding in pts at risk for a first bleeding
episode is therefore a major goal, medical Px consists of non-selective B-blockers (e.g. propranolol or carvedilol). Continuous
infusion of terlipressin reduces portal venous stably & may become an alternative to traditional bolus injection. Transjugular
intrahepatic portosystemic shunt (TIPS) has become a mainstay treatment opt for management of portal HTN related
complication in liver cirrhosis. Because of high perioperative mortality, transplantation should be avoided in those pts with
portopulmonary HTN who have severe HTN that is refractory to medical therapy. Drugs: non-selective B-blockers reduce portal
pressure in many pts: they reduce rates of bleeding & re-bleeding in pts with oesophageal varices; may also protect against
spontaneous bacterial peritonitis (perhaps through increasing intestinal transit), Carvedilol (a non selective B-blocker with anti-
alpha1-adrenergic effects) showed promising results. Nitrates: added to B-blocker therapy, they contribute to reducing portal
pressure & may reduce rates of variceal re-bleeding. Vasoactive drugs: terlipressin & octreotide are used to assist control of
acute variceal bleeding. Endoscopic procedures: endoscopy to detect & monitor oesophageal varices, endosopic vein ligation- to
prevent bleeding of oesophageal varices, for gastric varices with acute bleeding, endosopic variceal obturation with tissue
adhesives (e.g. cyanoacrylate) is effective- but there are recognised complications (mucosal ulceration & thromboembolism).
Transjugular intrahepatic portosystemic shunt (TIPS): a radiological procedure, connecting portal & hepatic veins using a stent.
Purpose is to decompress portal venous system, to prevent re-bleeding from varices to reduce formation of ascites, SE: hepatic
encephalopathy & deteriorating liver function. Stent may stenose- requires follow up and may require repeat procedures. An
established treatment for: ascites- for pts requiring repeated & frequent paracentesis. Oesophageal variceal bleeding refractory
to medical treatment. Bleeding from non-oesophageal varices- e.g. gastric varices. May have a role in: hepatorenal syndrome,
hepatic hydrothorax, hepatopulmonary syndrome, Budd-Chiary synd. Surgical procedures: surgical portosystemic shunts: less
likely to stenose than TIPS & can be used as TIPS alternative. Devascularisation procedures: inc gastro-oesophageal
devascularisation, splenectomy & oesophageal transection. Generally used where other therapies unsuitable.
 Portal HTN continued…

Management of rectal varices: common in pts with portal HTN but don’t usually
bleed- located in anorectal junction. If they bleed- suggested treatment is similar to
that used for upper GI varices- using drugs to reduce portal pressure, endoscopic
banding & TIPS if bleeding persists. Complications: bleeding from gastric or
oesophageal varices- most common complication. Gastric varices occur in around
20% of pts with portal HTN mostly secondary to liver cirrhosis. Ascites & its
complications: spontaneous bacterial peritonitis, hepatorenal synd, hepatic
hydrothorax. Pulmonary complications: portopulmonary HTN, hepatopulmonary
synd(triad of hepatic dysfunction, hypoxaemia, & extreme vasodilation in form of
intrapulmonary vascular dilatations. LF, hepatic encephalopathy, cirrhotic
cardiomyopathy.
GERD

Barrets, also barium may show hiatus hernia. Manometry=

 GERD

A condition which develops when the reflux of stomach contents cause troublesome symptoms (at least 2 heartburns
per/wk) and/or complications. Usually caused by dysfunction of lower oesophageal sphincter. If reflux is pro-
longed/excessive it may cause esophagitis, benign oesophageal stricture or barrets oesophagus. Several factors may
be a factor to reflux: hiatus hernia, lower oesophageal sphincter hypotension, loss of oesphageal peristaltic function,
abdominal obesity, gastric acid hyper secretion, delayed gastric emptying, overeating, smoking, alcohol, pregnancy,
surgery in achalasia, drugs (tricyclic's, anticholinergic’s, nitrates), systemic sclerosis, H.Pylori. Symptoms: oesophageal:
heartburn (burning, retrosternal discomfort related to meals, lying down, stooping and straining, relieved by antacids);
belching; acid brash (acid/bile regurgitation); water brash (excess salivation), odynophagia (painful swallowing e.g.
from esophagitis/ulceration). Extra-oesophageal: nocturnal asthma, chronic cough, laryngitis (hoarseness, throat
clearing) sinusitis. Complications: esophagitis, ulcers, benign stricture, barrets oesophagus (the epithelium of the
distal oesophagus undergoes metaplasia from squamous to columnar type. Endoscopic appearance can be described
as ‘velvety’ epithelium. Differential diagnosis: esophagitis (corrosive, NSAID); infection (CMV, herpes, Candida); DU;
gastric ulcers/cancers; non-ulcer dyspepsia. Tests: isolated symptoms do not require investigation. Do upper GI
endoscopy if: age>55yrs; symptoms >4wks; dysphagia; persistent symptoms despite treatment; relapsing symptoms;
weight ↓. Barium swallow may show hiatus hernia. 24h oesophageal pH monitoring +/- manometery help diagnose
GORD when endoscopy normal. Treatment: lifestyle: encourage: weight loss; smoking cessation, raise bed head; small
regular meals. Avoid: hot drinks, alcohol, citrus fruits, tomato's, onions, carbonated beverages, spicy foods, coffee,
tea, chocolate and eating <3hrs before bed. Avoid drugs affecting oesophageal motility or that damage mucosa
(NSAIDs, K+ salts, bisphosphonates). Drugs: antacids e.g. magnesium trisilicate mixture or alginates e.g. gaviscon
relieve symptoms. For esophagitis try a PPI e.g. lansoprazole. PPIs are more effective than H2 blockers.
Metoclopramide as monotherapy or adjunctive therapy for GORD is discouraged. Surgery: indicated only if symptoms
severe, refractory to medical therapy and there is severe reflux. Symptoms in pts with atypical symptoms (cough,
laryngitis) are less likely to improve with surgery compared with pts with typical symptoms.
 Pancreatic CA

Jaundice. dilated biliary tree (above). Below is

endscopic sonography (below).
Pancreatic CA
 Pancreatic cancer

Typical pt: male, >60yrs. Risk factors: smoking, alcohol, carcinogens, DM, chronic pancreatitis, and possibly a high
fat diet. Pathology: mostly ductal adenocarcinoma (metastasize early, present late). 60% arise in pancreas head,
25% in body, 15% in tail. A few arise in ampulla of vater or pancreatic islet cells- both have a better prognosis.
Genetics: ~95% have mutations in the KRAS2 gene. Symptoms and signs: tumours in head of pancreas present
with painless obstructive jaundice. 75% of tumours in body and tail present with epigastric pain (radiates to back
and relieved by sitting forward). Either may cause anorexia, DM, weight loss or acute pancreatis. Rarer features:
thrombophlebitis migrans (e.g. an arm vein becomes swollen and red, then a leg vein); Ca2+ ↑; marantic
endocarditis; portal hypertension (splenic vein thrombosis); nephrosis (renal vein metastases). Signs: jaundice +
palpable gall bladder, epigastric mass, hepatomegaly, splenomegaly, lymphadenopathy; ascites. Tests: Blood:
cholestatic jaundice. CA 19-9 ↑is non specific but may help assess prognosis. Imaging: US or CT can show a
pancreatic mass +/- a dilated biliary tree+/- hepatic metastases. EUS (endoscopic sonography) most accurate
diagnostic and staging tool compared to MRI and CT. ERCP shows biliary tree anatomy and may localise the site of
obstruction. Px: most ductal carcinomas present with metastatic disease; <10% are suitable for radical surgery.
Surgery: consider pancreatoduodenectomy if fit and tumour <3cm with no metastases. Post-op morbidity is high
and non curative resections provide no survival benefit. Post-op chemo delays disease progression. Palliation of
jaundice: endoscopic or percutaneous stent insertion may help jaundice and anorexia. Pain relief: disabling pain
may need big doses of opiates/radiotherapy. Coeliac plexus infiltration with alcohol may be done at time of
surgery or percutaneously. Prognosis: dismal. Mean survival <6months. 5yr survival <2%. Overall 5yr survival after
whipples procedure: 5-14%. Prognosis better if tumour <3cm; no nodes involves –ve resection margins at surgery;
ampullary or islet cell tumours.
tones

Gallstone in US.
 G all s t one s

Bile contains cholesterol, bile pigments (from broken down Hb), and phospholipids- if concentrations vary,
different stones may form. Pigment stones: (<10%) small, friable and irregular. Causes: haemolysis. Cholesterol
stones: large, often solitary. Causes: female, age, obesity (admirands triangle: ↑risk of stone, ↑cholesterol,
↓lethicin, ↓bile salts. Mixed stones: faceted (calcium salts, pigment, and cholesterol). Gall-stone prevalence: 8%
of those over 40yrs. 90% remain asymptomatic. Risk factors for stones becoming symptomatic: smoking, parity.
Acute cholecystitis follows stone or sludge impaction in the neck of the gallbladder (GB), which may cause
continuous epigastric or RUQ pain (referred to right shoulder), vomiting, fever, local peritonism, or a GB mass. The
main difference from biliary colic is the inflammatory component (local peritonism, fever, wcc ↑). If stone moves
to common bile duct, obstructive jaundice and cholangitis may occur. Murphy's signs: lay 2 fingers over the RUQ;
ask pt to breathe in- causing pain & arrest of inspiration as an inflamed GB impinges on your fingers. Its only +ve if
same test on LUQ doesn’t cause pain. A phlegmon (RUQ mass of inflamed adherent omentum & bowel) may be
palpable. Tests: WCC ↑, US- thick-walled, shrunken GB, pericholecystic fluid, stones, CBD- dilated if >6mm), HIDA
cholescintigraphy (useful is diagnosis uncertain after US). Plain AXR only shows ~10% of gallstones; it may ID a
‘porcelain’ GB (cancer?). Treatment: NBM, pain relief, IVI cefuroxime, consider cholecystectomy (laparoscopic if
no doubt GB perforation) within 72h; mortality: <1%. If delayed, relapse occurs in 18% & may be associated with
more complications, so early surgery often advised- otherwise operate after 6-12wks- if unsuitable then consider
percutaneous cholecystectomy; cholecystectomy can still be done later. Cholecystectomy also preferred
treatment for acalculous cholecystitis. Chronic cholecystitis: chronic inflammation +/- colic. ‘flatulent dyspepsia’:
vague abdominal discomfort, nausea, distension, flatulence and fat intolerance (fat stimulates cholecystokinin
release and GB contraction). US to image stones and assess CBD diameter. MRCP is used to find CBD stones. Px:
cholecystectomy. If US shows a dilated CBD with stones, ERCP + sphincterotomy before surgery. (if symptoms
persist post-cholecystectomy consider hiatus hernia/IBS/peptic ulcer/relapsing pancreatitis/tumour).
 Gallstones continued…

Biliary colic: gallstones are symptomatic with cystic duct obstruction or bypassing
into the CBD. RUQ (radiates->back) +/- jaundice. Px: analgesia, rehydrate, NBM.
Elective cholecystectomy. Urinalysis, CXR and ECG help exclude other diseases.
Other presentations: obstructive jaundice with CBD stones: if LFT worsening, ERCP
with sphincterotomy +/- biliary trawl then cholecystectomy may be needed, or
open surgery with CBD exploration. If CBD stones are suspected pre-op, intra-op
fluoroscopic cholangiography can be done. Cholangitis: (bile duct infection) causing
RUQ pain, jaundice and rigors. Treat with IV cefuroxime and metronidazole.
Gallstones ileus: a stone erodes through the GB into duodenum; it may then
obstruct terminal ileum. X-RAY: air in CBD (pneumobilia), small bowel fluid levels and
a stone. Duodenal obstruction is rarer. Pancreatitis. Mucocoele/empyema:
obstructed GB fills with mucus (secreted by GB walls)/pus. Silent stones: do elective
surgery on those with sickle cell, immunosuppression & all calcified/porcelain GBs.
Mirizzi’s syndrome: a stone in the GB presses on bile duct causing jaundice.
Gallbladder perforation: rare because of dual blood supply (hepatic artery via cystic
artery, & from small branches of hepatic artery in GB fossa).
Colorectal cancer

Barium enema shows apple core appearance shouldering (arrow) suggestive of colon
CA. 2nd on to right shows same thing.
Colorectal CA
 Colorectal cancer

3rd most common cancer and 2nd most common cause of cancer death. Usually adenocarcinoma. 56% of
presentations are in those >70yrs old. Synchronous tumours found in ~2.5% (metachronous tumours in ~1%).
Predisposing factors: neoplastic polyps, UC, Crohn’s, familial adenomatous polyposis, HNPCC, previous cancer,
low-fibre diet, smoking. NSAIDs and aspirin is protective. Genetics: no close relative affected: colorectal cancer
risk is 1:50. one 1st degree relative affected: risk=1:17, if 2 affected= risk is 1:10 (refer when 10yrs younger than
the youngest affected relative). Male=female equally. Prevention: trials suggest aspirin. Presentation: depends on
site: left-sided: bleeding/mucus PR; altered bowel habit/obstruction (25%); tenesmus; mass PR (60%). Right:
weight ↓, Hb ↓, abdominal pain, obstruction less likely. Either: abdominal mass; perforation; haemorrhage;
fistula. Tests: FBC (microcytic anaemia); faecal occult blood (FOB); sigmoidoscopy; barium enema/colonoscopy
can be done virtually by CT; LFT, CT/MRI; liver USS. CEA may be used to monitor disease and effectiveness of
treatment. If polyposis in family, refer for DNA test once >15yrs- may help determine who will benefit from
chemo. Spread: local, lymphatic, by blood (liver, lung, bone) or transcoelomic. Treatment: surgery: aims to cure
& may ↑survival times by up to 50%. Right hemicolectomy for caecal, ascending or proximal transverse colon
tumours. Left hemicolectomy for tumours in distal transverse or descending colon. Sigmoid colectomy for
sigmoid tumours. Anterior resection for low sigmoid/high rectal tumours. Abdomino-perineal (A-P) resection for
tumours low in rectum; perm colostomy and removal of rectum & anus. Hartmann’s procedure in emergency
bowel obstruction/palliation. Transanal endoscopic microsurgery allows local excision through a wide
proctoscope in those unfit for major surgery. Laparoscopic surgery is safe alternative to open approach.
Endoscopic stenting should be considered for palliation in malignant obstruction & as a bridge to surgery in acute
obstruction. stenting ↓need for colostomy, less complications than emergency surgery, shortens ICU & total
hospital stays and unnecessary ops.
 C olo rect al c an ce r co nti nue d…

Radio: may be used pre-op in rectal cancer to ↓local recurrence and ↑5yr survival.
It may be associated with a higher rate of post-op complication e.g. DVT,
pathological fractures, fistulisation. Pre-op radio +/- 5 FU is used to downstage
initially unresectable rectal tumours. Post-op radio is only used in pts with rectal
tumours at high risk of local recurrence. Chemo: good evidence adjuvant 5-FU +/-
other agents reduces duke’s C mortality~25%. Chemo also used in palliation of
metastatic disease. Surgery with liver resection may be curative if single-lobe
hepatic metastases and no extra-hepatic spread. Prognosis: 60% amenable to
radical surgery, 75% alive at 7yrs. Post-op anastomotic leakage shown to ↓survival
rates in otherwise potentially curative surgery. Imaging suspected leaks (↑T,
abdominal pain, peritonism) is with water soluble enema/CT. polyps are lumps that
appear above the mucosa. 1) inflammatory: UC, Crohn’s, lymphoid hyperplasia. 2)
Hamartomatous: Juvenile polyps, Peutz-Jeghers syndrome 3) Neoplastic:
Tubular/villous adenomas: malignant potential, esp if >2cm. Symptoms: passage of
blood/mucus PR. Should be biopsied and removed if show malignant change- most
can be reached by flexible colonoscope & diathermy can avoid morbidity of
colectomy.
 O es oph age al can ce r

Barium swallow showing stricture due to CA.

 Oesophageal cancer

Risk factors: diet, alcohol excess, smoking, achalasia, plummer-Vinson syndrome,

obesity, diet low in Vitamin A & C, nitrosamine exposure, reflux esophagitis +/0
Barret’s oesophagus. Male=female 5:1. Site: 20% occur in upper part, 50% in
middle, 30% in lower part- may be squamous or adenocarcinoma. The pt:
dysphagia; weight ↓; retrosternal pain, lymphadenopathy (rare). Signs from
upper 3rd of oesophagus: hoarseness; cough (may be paroxysmal if aspiration
pneumonia). Tests: barium swallow, CXR, oesophagoscopy with
biopsy/brushings/EUS, CT/MRI. Staging laparoscopy if significant infra-
diaphragmatic component. Treatment: survival rates poor with/without
treatment. If localised T1/T2 disease, radical curative oesophagectomy may be
tried. Transhiatal oesophagectomy causes less morbidity then extended
transthoracic resection, through the latter may be associated with ↑long-term
survival. Pre-op chemo (cisplatin + 5-FU) improves survival but causes some
morbidity. Surgery alone may be preferable. If surgery not indicated, chemo-radio
better than radio alone. Palliation in advanced disease aims to restore swallowing
with chemo-radio, stenting and laser use.
 Appendicitis

Appendicitis on US. Top mid pic shows abnormally dilated and thickened appendix in appendicitis. L pic shows same.
 appendicitis

Pathogenesis: gut organisms invade appendix wall after lumen obstruction by lymphoid hyperplasia, faecolith or
filarial worms. Leads to oedema, ischaemic necrosis and perforation. Symptoms: classically pre-umbilical pain that
moves to RIF. Anorexia is an important feature; vomiting rarely prominent- pain normally precedes vomiting in
surgical abdomen. Constipation usual. Diarrhoea may occur. Special tests: Rovsing’s sign: (pain >in RIF than LIF
when LIF pressed). Psoas sign (pain on extending hip if retrocaecal appendix) Cope sign (pain on flexion & internal
rotation of right hip if appendix in close relation to obturator internus). Investigations: blood tests: may show-
neutrophil leucocytosis & ↑CRP. USS may help-75% of tip of appendix located in retrocecal. Variations in clinical
picture: inflammation in a retrocecal/retroperitoneal appendix (2.5%) may cause RUQ pain- only sign may be
↑tenderness on right on PR. Boy with vague abdominal pain who will not eat his favourite food. Shocked,
confused octogenarian(80-89yo) who is not in pain. Appendicitis mortality high in pregnancy esp if >20wks
gestation- perforation commoner & ↑fetal mortality, pain is less well localised and signs of peritonism less
obvious. Hints: if child anxious- use his hand to press his belly. Check for recent viral illnesses & lymphadenopathy-
mesenteric adenitis? Don’t start palpating in RIF (makes it difficult to elicit pain elsewhere). Expect diagnosis to be
wrong half of time- if uncertain, re-examine often; don’t give antibiotics as it could cloud findings. Treatment:
prompt appendectomy. Antibiotics: IV metronidazole + cefuroxime. Give longer course if perforated.
Laparoscopy: useful because of diagnostic & therapeutic advantages esp in women and obese- CI in cases of
suspected gangrenous perforation as rate of abscess formation may be higher. Complications: perforation: a
commoner if a faecolith is present & in young children as diagnostic is more often delayed- doesn’t cause infertility
in girls. Appendix mass: may result when an inflamed appendix becomes covered with omentum. US/CT may help
with diagnosis- some advocate early surgery. Alternatively, initial conservative management- NBM (nil by mouth) &
antibiotics. If mass resolves, some perform interval appendectomy. Exclude colonic tumour with can result as early
as 4th decade. Appendix abscess: may result if appendix mass fails to resolve but enlarges & pt gets more unwell.
Treatment usually involves, drainage(surgical/percutaneous). Antibiotics alone can treat this.
 Pyloric stenosis

Usually presents not at birth but in first 3-8wks as projectile vomiting.

Male=female 4:1. baby is malnourished and always hungry. Diagnosis: palpate
pyloric mass in RUQ during feed. Visible gastric peristalsis starts in LUQ. Baby can
be severely alkalotic & depleted of water & ions from vomiting. Needs
correcting before surgery. USS may be useful in assessment. Pass NGT.
Treatment: Ramstedt’s pyloromyotomy (involves incision of muscle down to
mucosa). Pic below shows visible peristalsis. US shows hypertrophic pyloric
stenosis.
 Lactose intolerance

Top L pic shows soy intolerance.

 Lactose intolerance

Due to lack of enzyme lactase which hydrolyses lactose- enzyme essential in babies but tends to decrease after
age of 2, symptoms rare before age 6. milk intolerance in young children is due to allergy to cows milk and not
lactose intolerance. Lactose enhances absorption of Ca, Mg and Zn, also promotes growth of lactobacilli &
provides galactose- essential for formation of cerebral galactolipids hence development of brain. Types: primary
deficiency: develops at any age and autosomal recessive. Secondary: follows damage to intestinal mucosa e.g.
acute viral/bacterial gastroenteritis, IBD, chemo or uncontrolled celiac disease. More common in children esp in
developing world. Congenital: extremely rare autosomal recessive- complete absence of lactase, symptoms
apparent when milk introduced usually followed by intractable diarrhoea (cant be stopped even with med).
Developmental: occurs in preemie babies and improves once intestine matures. Epidemiology: higher in
Hispanics lower in north Europeans. More common in societies where dairy products less consumed. Risk
factors: symptoms caused only by ingested dairy or milk products- affected by quant. And how fast small
intestine presented with lactose load- more marked if lactose reaches intestine mucosa fast but slow if gastric
emptying delayed e.g. when eaten with large meal. Symptoms: gas build up causes: bloating, flatulence,
abdominal discomfort. Acidic and osmotic effects of undigested lactose may cause: loose water stool- with
degree of urgency an hr or 2 after milk ingestion and perianal itching due to acidic stools. Secondary may
produce worse symptoms and dehydration. Exam: may be malnutrition & failure to thrive but its uncommon.
Adults= usually nothing, little bloating & discomfort during attack. Investigations: hydrogen breath test- if carbs is
unabsorbed in gut, it is fermented by bacteria in large intestine and H2 gas is produced, absorbed into blood and
excreted by lungs- thus H2 can be measured after a carb workload. Normally bacteria are confined to small
intestine but when bacterial overgrowth occurs, upper small bowel fermentation of ingested lactose occurs &
causes early rise in exhaled H2 conc. Antibiotics may produce false neg. Differentials: allergy to milk proteins or
other constituents, deficit of other disaccharides, infantile colic, IBD, diverticular disease, UC, celiac disease, CF.
 Lactose intolerance continued…

Management: avoid milk & dairy products will relieve symptoms however will cause lack of
calcium esp if veggy diet. Most pts could tolerate a glass of milk per/d. Primary: varying
amounts of lactose can be tolerated esp if divided throughout day. Yogurt & curds may be
tolerated due to thicker texture & slower gastric empting & partially hydrolysed already-
live yogurts have own bacteria which partly hydrolyse own lactose. Diary products high in
fat content e.g. ice cream, full-fat milk and cheese etc. better tolerated as it slows gastric
emptying. Hard cheese e.g. cheddar may be better tolerated as it contains very little
lactose. Milk substitutes- less nutrients. Lactase enzyme preps- expensive. Secondary: resus
with IV rehydration may be required occasionally. Antibiotics avoided unless strongly
required. Formula/breast milk/regular milk must still be given during acute diarrhoea,
alternatives given to high-risk cases. Developmental: tube feeding with milk containing half-
strength lactose formula/breast milk. Complications: most people suffer very little but
babies with severe deficiency require diet full of nutrients exc lactose. Transient lactose
deficiency affects significant no. of infants with severe gastroenteritis & diarrhoea.
Improper feeding with lactose can lead to chronic diarrhoea & malnutrition. Lactose
enhances absorption of several vitamins e.g. Ca, Mg, Zn thus Ca supplements highly
needed. Prevention: bread, cakes, cereals, Margarine, dressings, sweets, snacks various
drugs.
D ive rtic ula
Diverticula
 Diverticula

An out pouching of gut wall usually sites of perforating arteries. Diverticulosis means diverticula are present &
diverticula disease means they are symptomatic. Pathology: most occurs in sigmoid colon with 95% complications
at this site but right-sided & massive single diverticula can occur. Lack of dietary fibre thought to lead to high
intraluminal pressures which force mucosa to herniate through muscle layers of gut at weak points adjacent to
penetrating vessels, 30% of westerners thought to have diverticulosis by 60yrs. Diagnosis: PR exam- may reveal
abscess/colorectal cancer, chief competing diagnosis; sigmoidoscopy; barium enema; colonoscopy; CT may be
more useful than US & plain film may only be useful in showing vesical fistulae (air in bladder). Complications:
may be altered bowel habit +/- left-sided colic (severe pain in abdomen caused by wind/obstruction in intestines)
relieved by defecation; nausea; flatulence. High fibre diet may be tried. Antispasmodics e.g. mebeverine may
help. Surgical resection occasionally resorted to. Others: perforation: ileus (painful obstruction of ileum),
peritonitis +/- shock. Mortality: 40%. Manage as for an acute abdomen. At laparotomy a Hartman’s procedure
may be performed (temp colostomy + partial colectomy). Possible to do colonic lavage via appendix stump, then
immediate primary anastomosis. Haemorrhage: usually sudden and painless- common cause of big rectal bleeds-
usually stops with bed rest. Transfusion may be needed. Embolisation/colonic resection may be necessary after
locating bleeding points by angiography/colonoscopy. Fistulae: enterocolic, colovaginal or colovesical
(pneumaturia +/- intractable UTIs). Treatment is surgical e.g. colonic resection. Abscesses e.g. with swinging fever,
leucocytosis and localising signs e.g. boggy rectal mass (pelvic abscess-drain rectally). If no localising signs,
remember aphorism: pus somewhere, pus nowhere= pus under diaphragm. A sub phrenic abscess is a horrible
way to die so do urgent US. Antibiotics +/- US/CT-guided drainage may be needed. Post-infective strictures may
form in sigmoid colon.
 Hepatitis

Top mid pic shows symptoms for Hep A.

 Hepatitis- viral

Hep A virus: RNA virus. Spread: faecal-oral, often in travellers/institutions. Most infections occur in childhood. Incubation: 2-
6wks. Symptoms: prodromal symptoms inc fever, malaise, anorexia, nausea, arthralgia. Jaundice develops +/-
hepato/splenomegaly & adenopathy. Tests: AST & ALT rise from d25 after exposure & usually return to normal over 5-20wks.
IgM rises from day 25 & signifies recent infection. IgG remains detectable for life. Treatment: supportive. Avoid alcohol.
Rarely, Inf-alpha for fulminant (severe & sudden) hepatitis. Hep B virus: (HBV-Dna virus): spread: blood products, IV drug
abusers (IVDU), sex intercourse, direct contact. Deaths: 1m/yr. Risk groups: IV drug users & sex partners; health workers;
haemophiliacs & their carers (exposure to blood products- also morticians/embalmers); haemodialysis (&chronic renal
failure); sexually promiscuous; foster carers; close family members of a carrier or case; staff/residents of day care or long-
term institutions/prisons; babies of HbsAg +ve mothers; adopted child from endemic area. Endemic in: far east, Africa &
Mediterranean. Incubation: 1-6months. Signs: resemble hepatitis A but extra-hepatic features are more common e.g.
arthralgia, urticarial. Tests: HBsAg (surface antigen) is present from 1-6months after exposure. HBeAg (e antigen) is present
for 1.5-3 months after acute illness & implies high infectivity. Persistence of HBsAg for >6months defines carrier status &
occurs in 5-10% of infections (chronic). Antibodies to HBcAg (anti-HBC) imply past infection; antibodies to HBsAg (anti-HBs)
alone imply vaccination. HBV PCR allows monitoring of response to therapy. Vaccination: may be universal/childhood or just
for high risk groups. Passive immunisation may be given to non-immune contacts after high-risk exposure. Px: supportive.
Avoid alcohol. Chronic HBV may respond to PEGinteferon alfa-2a or others antivirals. Immunise sexual contacts.
Complications: fulminant hepatic failure (rare); relapse; pro-longed cholestasis; chronic hepatitis (5-10%); cirrhosis;
hepatocellular carcinoma (hcc:10-fold ↑risk if HBsAg +ve, 60fold ↑risk if both HBsAg and HBeAg +ve; preventable by
interferon esp. in HBeAg-positive Asians.); glomerulonephritis; cryoglobulinaemia. Hep C virus (HCV): RNA flavivirus. Spread:
blood: transfusion, IV drug abuse; sex; acupuncture. Early infection is often mild/asymptomatic. ~85% develop chronic
infection; 20-30% get cirrhosis within 20yrs; few get hepatocellular cancer (hcc). Tests: LFT (AST:ALTM1:1 until cirrhosis
develops), anti-HCV antibodies, recombinant immunoblot assay, HCV-PCR, liver biopsy if HCV-PCR +ve to assess liver damage
& need for treatment. Treatment: untreated- accelerates progression of HCV-induced liver fibrosis. Given safety & efficacy of
co-therapy with PEGinf + ribavirin & bad effects of chronic hep C, all HIV/HCV co-infected pts should be evaluated for therapy.
 Hepatitis- viral con tinued…

Hepatitis D virus (HDV) incomplete RNA virus, exists only with HBV. Spread: with
HBV. Signs: ↑risk of acute hepatic failure & cirrhosis. Tests: anti-HDV antibody.
Treatment: Inf-alpha has limited success in treatment of HDV infection. Hep E
virus (HEV) RNA virus. Similar to HAV; common in Indochina. High mortality in
preganancy. Hepatitis GB: parentally transmitted. Causes asymptomatic post-
transfusion hepatitis. One type (HGB-C) can cause fulminant liver failure.
Hepatitis

Jaundiced pt
C hron ic ren al f ail ure (dis ea s e)
 Chronic renal failure

US above shows small kidneys. Far right pic shows cysts on kidney. XRAYS shows osteodystrophy in CRF. Histology A shows normal glomerulus but B & C show scarring in CRF.
 Chronic renal failure

Kidney damage for >3months based on abnormal functions. Stage 1: (GFR >90), normal/ ↑GFR with other
evidence of renal damage. Stage 2: (GFR 60-89) slight ↓GFR with other evidence of renal damage. Stage 3 A:
(GFR 45-59) moderate ↓GFR with/without evidence of other renal damage. Stage 3 B (GFR 30-44) stage 4 (GFR
15-29) severe ↓GFR with/without evidence of renal damage. Stage 5 (GFR <15) established renal failure.
Symptoms usually occur once stage 4 reached. Causes: common: BP ↑, & DM. also: glomerulonephritis, reno-
vascular disease, pyelonephritis, polycystic disease, BPH (benign prostatic hyperplasia), interstitial nephritis,
analgesic nephropathy, renal stones. Rare: myeloma, amyloidosis, SLE, scleroderma, vasculitis, HUS,
nephrocalcinosis, gout, renal tumour, alports syndrome, Fabry’s disease. History: ask about: Past UTI, known
↑BP, DM, family history. Take careful drug history. Any fatigue, weakness, anorexia, vomiting, metallic taste,
pruritis (severe itching of skin), restless legs, bone pain, impotence/infertility? Symptoms are common when urea
>40mmol/L. dyspnoea, ankle swelling (fluid overload?) screening: high risk groups should be screened for CRF:
DM, ↑BP, age >60, recurrent UTIs, urinary obstruction, systemic illness affecting kidneys e.g. SLE, CVD, structural
renal tract disease, renal stones, BPH, family history of stage 5/heredity kidney disease, opportunistic detection
of haematuria/proteinuria. Signs: pallor (unhealthy appearance), yellow skin pigmentation, brown nails, purpura
(rash of purple spots on skin caused by internal bleeding of small vessels)bruising, excoriation (wearing of skin),
BP ↑, cardiomegaly, pericardial rub, pleural effusion, pulmonary/peripheral oedema, proximal myopathy, (+
cause e.g. DM: peripheral neuropathy, retinopathy). Later if untreated: arrhythmias, encephalopathy, seizures
and coma. Tests: Blood: Hb ↓, ESR, U&E, (↑urea, ↑creatinine), glucose (DM), ↑PO4, ↑alk phos (renal
osteodystrophy) ↓Ca, ↑PTH (hyperparathyroidism). Urine: MC&S, dipstick, 24h urine protein. Imaging: renal US,
usually small <9cm but may be normal/large with CRF in DM, polycystic kidney disease, amyloidosis, myeloma,
systemic sclerosis, asymmetric renal vascular disease. CXR: cardiomegaly, pleural/pericardial effusions/pulmonary
oedema. Bone X-RAYs may show renal osteodystrophy. Renal biopsy: if cause unclear and normal size kidneys.
 Chronic renal failure management continued…

Treat reversible causes: relieve obstruction, stop nephrotoxic drugs, deal with Ca
↑and CVD risk. Lifestyle advice: CKD should take exercise, achieve a healthy weight
& stop smoking. Match dietary & fluid intake with excretion. Na+ restriction: helps
control BP & prevent oedema. A moderate protein diet is recommended. K+
restriction only if hyperkalaemia; HCO3 supplements to correct acidosis. ↑BP: even a
small BP drop may save significant function. Target BP <140/85. diabetic kidney
disease, even with normal BP, treat with ACE-I or ARA. CVD: in CKD stages 1 & 2, risk
from CVD death higher than risk of reaching ESRF. Give statins to CKD pts irrespective
of baseline lipid values. Give aspirin also (↑risk of bleeding-beware). Anaemia: exc
IDA (iron-def) & chronic infection; consider EPO. Renal bone disease
(osteodystrophy) treat if ↑PTH. PO4 rises in CRF, which ↑PTH further & also
precipitates in kidney & vasculature. Restrict dietary PO4 (milk, cheese, eggs). Give
binders e.g. calcichew to bind PO4 in gut to ↓its absorption. Vit D analogues e.g.
alfacalcidol & Ca supplements to ↓bone disease & hyperparathyroidism. Oedema:
high dose loop diuretics may be needed (furosemide) +/- metolazone & restrict
fluid + Na intake. Restless legs: clonazepam/gabapentin. Prep for dialysis/transplant.
Autosomal dominant PCKD
Autosomal dominant PCKD

US shows cysts with bilaterally enlarged kidneys.

 A uto s om al dom in an t po lyc ys t ic k id ney di s ea s e

Genes on chromosomes 16 and 4 affected. Signs: renal enlargement with cysts,

abdominal pain +/- haematuria (haemorrhage into cyst), cyst infection, renal
calculi, BP ↑, progressive renal failure. Extra-renal: liver cysts, intracranial
aneurysm->SAH (subarachnoid haemorrhage, which may present with very
severe headache requiring immediate attention), mitral valve prolapse. Px:
monitor U&E. ↑BP should be treated aggressively, with target levels of <130/80
(ace-I are best choices). Treat infections, dialysis/transplant for ESRF; genetic
counselling. Pain may be helped by laparoscopic cyst removal/nephrectomy.
↑water intake, ↓Na+ intake, & avoiding caffeine may help. Screening for SAH
with MR-angiography may be done in 1st degree relatives of those with SAH +
ADPKD. Some screen with no family history, esp for certain occupations e.g.
pilots.
Acute renal failure
 Acute renal failure

Enlarged kidney in acute renal failure.

 Acute renal failure

A significant deterioration in renal function occurring over hours/days, clinically manifested as abrupt rise in serum
urea & creatinine. May be asymptomatic but oliguria (small amounts) is common. Life threatening consequences inc:
volume overload, K+ ↑, metabolic acidosis. ARF may arise as isolated problem but most commonly occurs in setting of
circulatory disturbances e.g. severe illness, sepsis, trauma or surgery or in context of nephrotoxic drugs. ARF common
esp in pts with DM, ↑BP & elderly. Causes: pre-renal failure & acute tubular necrosis (ATN) account for >80%. 1) pre-
renal (40-70% of cases): due to renal hypoperfusion e.g. hypovolaemia, sepsis (causing systemic vasodilation), CCF,
cirrhosis, renal artery stenosis, NSAIDs or ACE-I (these interfere with renal blood flow). 2) Intrinsic (10-50% cases): ATN
is damage to renal tubular cells caused by ischaemia (which causes renal hypoperfusion) or nephrotoxins: often due to
drug, radiological contrast agents, uric acid crystals, haemoglobinuria or myeloma. Recovery of renal function occurs
within weeks but mortality remains ~50%. Others: vascular, vasculitis, malignant ↑BP, cholesterol emboli, HUS, GN,
interstitial nephritis; hepatorenal syndrome. 3) post-renal: (10% of cases); due to UT obstruction. Assessment: 1) is
renal failure acute/chronic? Suspect chronic renal failure if: history of comorbidity e.g. DM, ↑BP, long duration of
symptoms, previous abnormal tests. Small kidneys on US, with ↑echogenicity (return signals). Presence of anaemia,
PO4 ↑, Ca ↓, may not differentiate between CRF and ARF as these can occur within days however their absence
suggests ARF. 2) is there a UT obstruction?- should always be considered as cause of ARF as its reversible & prompt
treatment prevents perm renal damage- should be suspected in pts with single kidney/history of renal stones, BPH
(benign prostatic hyperplasia) or previous pelvic/retroperitoneal surgery. Exam for palpable bladder, pelvic/abdominal
masses or enlarged prostate. Complete anuria (failure to produce) suggests renal tract obstruction & is unusual in ARF.
Renal US is preferred method to detect dilatation of renal pelvis & calyces although obstruction may be present
without dilatation esp in malignancy. 3) is there a rare cause of ARF- e.g. glomerulonephritis- usually associated
haematuria/proteinuria, & warrant urgent renal referral for consideration of renal biopsy & treatment. Tests: blood
tests: U&E (beware K+ ↑), FBC, LFT, clotting, CK, ESR, CRP. Consider ABG, blood cultures & also hepatitis serology. If
dialysis considered. If cause unclear, consider: serum Immunoglobulin's, electrophoresis, complement levels,
autoantibodies and ASOT.
 Acute renal failure continued…

Tests: urine: dipstick for leucocytes, nitrite, blood protein, glucose. Microscopy for RBC, WBC, crystals, casts. Culture &
sensitivity. Chem: U&E, creatinine, osmolality, bence-jones protein. CXR: pulmonary oedema. ECG: signs of hyperkalaemia?
Renal US: renal size/obstruction? Management: treat shock if cause (↓intravascular volume). Urgent US, must check for
palpable bladder- its absence doesn’t rule out obstruction. Find & treat exacerbating factors: e.g. hypovolaemia, sepsis, BP
↑. Stop nephrotoxic drugs- NSAIDs, ACE-I, gentamicin, vancomycin, amphotericin. Stop metformin if creatinine >150mmol/L.
signs of vasculitis?- nosebleeds, haematuria, rash, ESR/CRP ↑, do autoantibodies. Assessing signs of ↓intravascular volume
can be difficult, look for ↓urine volume, invisible JVP, poor tissue turgor, ↓BP, ↑pulse. When in doubt consider inserting CVP
line to measure venous pressure. Signs of fluid overload: gallop rhythm on cardiac auscultation, ↑BP, ↑JVP, lung
crepitation's, peripheral oedema. Consider transfer to ICU. Pulse, BP, CVP, urine output hourly. Daily fluid balance + weight
chart. Match input to loss + 500mL for insensible loss (more if T ↑). Correct volume depletion with IV fluid-
colloid/saline/Blood (only of hyperkalaemia not a problem). If pt septic= take cultures & treat with antibiotics- Remove any
potential sources of sepsis when no longer required e.g. catheter, IV. Re-check for any nephrotoxic drugs; adjust doses for
renally excreted drugs. Nutrition is vital aim for normal calorie in take & protein~0.5g/kg. if oral intake poor consider
nasogastric feed early (parenteral if impossible). Treat complications: hyperkalaemia may cause arrhythmias/cardiac arrest.
ECG changes: tall ‘tented’ T waves; small/absent P wave; increased PR interval; widened QRS complex; ‘sine-wave’ pattern;
asystole. Px: IV calcium- cardioprotective. IV insulin + glucose- insulin stimulates intracellular uptake of K+, check capillary
glucose. Salbutamol, consider calcium resonium- works over a longer period, SE: constipation. Haemodialysis usually
required of anuric. Pulmonary oedema: sit up & give high-flow O2 by face mask. Give venous vasodilator e.g. morphine IV,
furosemide IV, if no response, urgent haemodialysis. Consider CPAP therapy and venesction if pt is in extremis. IV nitrates.
Bleeding: impaired haemostasis due to ↑urea may be compounded by precipitating cause. Give PPIs/H2 antagonist. In case
of active bleeding give: fresh frozen plasma & platelets as needed if clotting problems. Blood transfusion. Desmopressin to
↑factor VIII activity, normalising bleeding time. Indications for acute dialysis: refractory pulmonary oedema, persistent
hyperkalaemia, severe metabolic acidosis or base excess, uremic encephalopathy, uremic pericarditis. Prognosis: worse if
oliguric. Mortality depends on cause: burns (80%), trauma/surgery (60%), medical illness (30%), obstetric/poisoning (10%).
 Renal calculi

US above shows renal calculus.

Renal calculi
 Renal calculi

Renal stones consist of aggregates- form in collecting ducts & deposited anywhere from renal pelvis to urethra
through classically at 1) Pelvi-uteric junction 2) pelvic brim 3) vesico-uteric junction. Prevalence: common: lifetime
incidence up-to 15%. Peak-age: 20-40yrs, male: female 3:1. Types: Calcium oxalate (75%), Mg ammonium
phosphate (10-20%). Also: urate (5%), hydroxyapatite (5%), brushite, cysteine (1%), mixed. The pt: asymptomatic or:
1) renal colic: excruciating spasms ‘loin to groin’, often with nausea/vomiting. Often cannot lie still (differentiates
from peritonitis). Renal obstruction: felt in loin, between rib 12 & lateral edge of lumbar muscles (like intercostal
nerve irritation pain; latter is not colicky(abdominal) & worsened by specific movements/pressure on trigger spot).
Obstruction of mid-ureter may mimic appendicitis/diverticulitis. Obstruction of lower ureter may lead to symptoms
of bladder irritability & pain in scrotum, penile tip or labia majora. Obstruction in bladder or urethra causes pelvic
pain, dysuria, strangury (desire but inability to void) +/- interrupted flow. 2) UTI can co-exist: (↑risk of voiding
impaired); pyelonephritis (fever, rigors, loin pain, nausea and vomiting), pyelonephrosis 3) haematuria 4) proteinuria
5) sterile pyuria (↑wcc in urine which are sterile) ( 6) anuria. Exam: usually no tenderness/palpation. May be renal
angle tenderness esp to percussion if there is retroperitoneal inflammation. Tests: FBC, U&E, Ca2+, PO4, glucose,
bicarbonate, urate. Urine dipstick: usually +ve for blood (90%). MSU: MC&S. further tests for cause: urine pH; 24h
urine for: Ca2+, oxalate, urate, citrate, Na, creatinine; stone biochem. Imaging: KUB XR (kidneys ureter + bladder).
Look along ureters for calcification over transverse processes of vertebral bodies: 80% of stones are visible. IVU:
radio-opaque contrast injected & serial films taken until contrast seen down to level of obstruction. Abnormal
findings: failure of contrast to flow to bladder, dense nephrogram, clubbed/blunted renal calyces, filling defects in
bladder. USS: to look for hydronephrosis or hydroueter. Spiral non-contrast CT is superior to & is replacing IVU for
imaging stones & helps exclude differentials of acute abdomen-> ruptured AA may present similarly.
 R en al ca lcul i co nti nue d…

Px: initially: Analgesia e.g. diclofenac + IV fluids if unable to tolerate PO; cefuroxime if
infection. Stones <5mm in lower ureter ~90-95% pass spontaneously. ↑fluid intake. Sieve
urine for analysis. Stones >5mm not resolving: medical expulsive therapy: nifedipine or
Alpha-blockers e.g. tamsulosin +/- prednisolone promote expulsion-> start at
presentation. Most pass within 48h, if not try ESWL/ureteroscopy using ‘dormier basket’.
Shock-wave lithotripsy (ESWL), SE: renal injury- may cause ↑BP & DM. percutaneous
nephrolithotomy (PCNL) keyhole surgery to remove stones, when large, multiple or
complex. Indications for urgent intervention: (delay lead to perm loss of renal function):
presence of infection + UT tract obstruction (percutaneous nephrostomy may be needed
to relieve obstruction), urosepsis, intractable pain or vomiting, impending ARF, obstruction
in a solitary kidney, bilateral obstructing stones. Prevention: general: drink plenty. Normal
Ca2+ intake is now recommended as low intake leads to ↑oxalate excretion. Ca2+ stones:
in hypercalciuria, a thiazide diuretic is used to ↓Ca2+ excretion. Oxalate: ↓oxalate intake,
pyridoxine may be used. Struvite: treat infection promptly. Urate: allopurinol. Urine
alkalinisation may also help as urate is more soluble at pH>6. cysteine: vigorous hydration
to keep urine output >3L/day & urine alkalinisation. D-penicillamine is used to chelate
cysteine, given with pyridoxine to prevent vitamin B6 deficiency.
 Nephritic synd rome

Biopsy findings show inflamed glomeruli fills up most of bowman capsule on top left pic. Dysmorphic RBCs on right pics.
 IgA nephropathy (Berger’s disease)

Pic on far right shows: Proliferative IgA nephropathy, with cellular crescent, increased mesangial matrix and mesangial and endocapillary
hypercellularity. Bottom left biopsy shows mesengial hypercellularity. Bottom middle shows RBC casts.
 Anti-GBM d isease (goo d pastures disease)

Cresent formation of cells on bottom left pic.

Proliferative GN

Top right pic shows acute proliferative GN.

 henoch-schonlein purpura (hsp)

Biopsy similar to IgA nephropathy, so: cellular crescent, increased mesangial matrix and mesangial and endocapillary hypercellularity
etc.
 Ra pidl y p rog re s s iv e G N (R PG N)

Top 2 right pics both show cresentic (rapidly progressive) GN.

 glomerulonephritis

Common cause of ESRF in adults, along with diabetes/hypertension. Group of disorders where damage to GF
apparatus cause leak of protein +/- blood into urine, depending on disease. Pts may be asymptomatic/present with
haematuria (may be microscopic +/- red cell casts), proteinuria, renal failure/hypertension. Tests: blood: FBC, U&E,
LFT, ESR, CRP, immunoglobulin's, electrophoresis, complement, autoantibodies, ANA, ANCA, anti-dsDNA, anti-GBM,
blood culture, ASOT, HBsAg, anti-HCV. Urine: RBC casts, MC&S, Bence-Jones protein. 24h urine: protein. Use spot
(early morning) urine sample for protein: creatinine ratio or albumin: creatinine ratio as these tests less prone to
error, give quicker results & have been shown to be as accurate as 24h urine collections. CXR, renal US +/- renal
biopsy. Nephritic syndrome: haematuria with RBC casts +/- dimorphic RBCs, proteinuria, ↑BP & progressive oliguria
& renal impairment. Management: refer to nephrologist. Keep BP <130/80. inc ace-I or ARA- or both. IgA
nephropathy (Berger’s disease): commonest GN in developed world. Most present with macro-microscopic
haematuria; occasionally nephritic syndrome (haematuria + RBC casts). Typical pt: young male with episodic
macroscopic haematuria occurring few days after URTI e.g. pharyngitis. Recovery often rapid between attacks. ↑IgA
possibly due to infection forming immune complexes & deposits in mesengial cells. Renal biopsy: mesengial
proliferation, immunofluorescence shows deposits of IgA & C3. Px: immunosuppression (role debated), steroids may
↓proteinuria & slow decline of renal function. Cyclophosphamide may also be effective in some pts with rapidly
deteriorating renal function. Prognosis: worse if ↑BP, male, proteinuria or renal failure at presentation. 20% of adults
develop ESRF over ~20yrs. Systemic lupus erythematous (SLE): 1/3 of pts with SLE will have evidence of renal
involvement with vascular, glomerular & tubulointerstitial damage. Anti-glomerular basement membrane (GBM)
disease: known as Good pasture's disease, caused by development of auto-antibodies to type IV collagen, an
essential component of GBM. Type IV collagen also is found in lung & haemoptysis may be a feature esp in smokers.
Young males most commonly affected but can occur in any age/gender. Pts present with macroscopic haematuria,
progressing rapidly to oliguria. Renal failure may occur within days of onset of symptoms. If treatment (plasma
exchange, corticosteroids +/- cytotoxic’s) started early, the disease can be cured & relapses are rare.
 Glomerulonephritis (GN)

Proliferative GN classified histologically: focal, diffuse or mesangiocapillary GN. Chief cause is post-
streptococcal GN (diffuse proliferative GN), occurring 1-12wks after sore throat/skin infection. A strep
antigen is deposited on glomerulus causing host reaction & immune complex formation. Presentation:
usually nephritic syndrome. Renal biopsy: inflammatory reaction affecting mesangial & endothelial
cells, IF: IgG & C3 deposits. Serology: ↑ASOT(antistreptolysin O titer- blood test looking for antibodies
to strep A bacteria), C3 ↓. Treatment: supportive >95% recover renal function. Henoch- Schonlein
purpura (HSP) systemic variant of IgA nephropathy, causing small vessel vasculitis. Features: purpuric
rash on extensor surfaces (typically legs), fitting polyarthritis, scrotal & scalp swelling, abdominal pain
(GI bleeding) & nephritis. Diagnosis: usually clinical. Confirmed with +ve IF or IgA & C3 in skin or renal
biopsy (similar to IgA nephropathy). Treatment: same as IgA nephropathy. Prognosis: 15% nephritic
pts -> ESRF; if both nephritic & nephrotic syndrome, 50% ->ESRF. Rapidly progressive GN (RPGN) most
aggressive GN- potential to cause ESRF over days. Different causes; all have biopsy finding of cresents
affecting most glomeruli. RPGN classified pathologically into 3 categories: 1) immune complex disease
(~45% of cases): post-infectious, multi-system disease, IgA nephropathy, Henoch-Schonlein purpura. 2)
Pauci-immune disease, wegner’s granulomatosis, microscopic polyangitism Churg-Struass. 3) anti-GBM
antibody disease: good-pastures disease. Clinically: signs of renal failure. May be features of individual
systemic disease. Massive PE haemorrhage most common cause of death in ANCA +ve pts. Treatment:
aggressive immunosuppression with high-dose corticosteroids & cyclophosphamide + plasma
exchange to remove existing antibodies. Prognosis: poor if initial serum creatinine >600umol/L. below
this, ~80% have some improvement of renal function with treatment.
Nephrotic syndrome
 Neph rotic sy ndrome- minimal ch an ge GN

Top left shows: The interstitium is mildly oedematous. The tubules are unremarkable. Far right shows same.
Neph rotic sy ndrome- membranous nephrop athy
Focal segmental glomeruloscelerosis- nephrotic syn

Typical lesions.
N eph roti c s ynd ro me - Th in b as em en t m em bran e n ep hro pa thy
 Nephrotic syndrome

Triad of: proteinuria, hypoalbuminaemia & oedema. Severe hyperlipidaema often present. Na+ retention in
extracellular compartment & molecular changes in capillary barrier causes oedema. Clinical features: ask about
acute/chronic infections, drugs, allergies, systemic symptoms. Signs: oedema, typically pitting and dependant. It
occurs periorbitally & peripherally in limbs- genital oedema, ascites and anasarca (extreme generalised oedema)
develop later. BP ↑, or ↓, CCF (congestive cardiac failure- ↑JVP, pulmonary oedema, mild proteinuria) /liver
disease (↓albumin). Complications: ↑chance of infections, occurs in 20% of adult pts due to ↓serum IgG,
↓compliment activity, ↓T cell function (from treatment & Ig loss). Thromboembolism: up-to 40% e.g. DVT/PE,
renal vein thrombosis- partially due to ↑clotting factors & platelet abnormalities. Hyperlipidaema: ↑cholesterol &
triglycerides, thought to be due to hepatic lipoprotein synthesis due to low oncotic pressure. Tests: as for GN +
check cholesterol. Renal biopsy: do in all adults. In children, most have minimal change GN so course of steroids
tried initially. Biopsy for those whose proteinuria not reduced after 1m/or if features suggest another cause e.g.
age <1yr, fam Hx, extra-renal disease (arthritis, rash, anaemia), renal failure, haematuria. Minimal change
glomerulonephritis (MCGN): commonest cause of nephrotic syndrome in children- thought to be T cell mediated
& may rarely present with haematuria/ ↑BP. Associations: Hodgkin’s lymphoma, drugs (e.g. NSAIDs) Tests:
selective proteinuria: only smaller proteins leaked e.g. albumin. Renal biopsy: normal on light microscopy, EM:
fusion of podocytes. Px: 95% of children & 70% of adults undergo remission with steroids but prone to relapse.
Cyclophosphamide/ciclosporin are used if frequent relapses/steroid SE/dependence. Prognosis: ~1%-> ERSF.
Membranous nephropathy: accounts for 20-30% of nephrotic syndrome in adults; 2-5% in children. Unknown
cause: associations: malignancy, drugs, autoimmune, infections. Presentations: usually nephrotic syndrome. Risk of
renal vein thrombosis. Diagnosis: biopsy shows diffuse thickened GBM: IF shows IgG and c3 subepthelial deposits.
Treatment: based on poor diagnostic factors: ie deteriorating renal function, heavy proteinuria. Steroids +
cyclophosphamide/chlorambucil are considered if renal function deteriorates. Prognosis: 40% will have
spontaneous remission.
 Nephrotic syndrome continued…

Mesnangiocapillary: GN: a rare GN, often presenting with nephrotic syndrome. Biopsy shows large glomeruli:
mesengial proliferation & thickened capillary walls -> ‘tramline’ appearance of double BM. Type I (sub-endothelial
immune deposits): Idiopathic/seen with HCV, endocarditis, visceral abscess, infected arteriovenous shunts, HBV. ↓C4
levels; type 2: (intramembranous deposits): sometimes with partial lipodystrophy, ↓serum C3 and +ve C3 nephritic
factor. Px: none proven of benefit so far; steroids used in children & rituximab. Prognosis: 50% develop ESRF- can recur
in transplants. Focal segmental glomeruloscelerosis (FSGS) may be primary (idiopathic) or secondary, HIV also
associated. Presentations: usually nephrotic syndrome/proteinuria ~50% have impaired renal function. Renal biopsy:
some glomeruli scarring of certain segments, IF (immunofluroresence): IgM & C3 deposits in affected areas. Px:
responds to corticosteroids in ~30%. Cyclophosphamide/ciclosporin are considered if steroid-resistant. Prognosis: 30-
50%-> ESRF. It recurs in 20-50% of transplant kidneys which may respond to plasma exchange. Thin basement
membrane nephropathy: genetic cause, autosomal dominant: persistent microscopic haematuria, rarely minor
proteinuria. Diagnosis: renal biopsy: thin glomerular BM on EM. Prognosis: usually benign. Small risk of CRF, preceded
by ↑BP & proteinuria-monitor 1-2yearly. General measures: monitor U&E, BP, fluid balance & weight regularly. Cause
of oedema is Na+ retention so ↓Na+ intake and ↑water intake. In adults, diuretics often used e.g. furosemide +/-
metolazone/spironolactone with monitoring U&E. proteinuria independent risk factor for CVD- use ACE-I or A2A, they
↓proteinuria. Treat infections promptly. Pneumococcal vaccinations recommended. Muscle wasting major problem-
keep protein intake normal as ↓intake will lead to malnutrition. Treating underlining cause of nephrotic syndrome will
resolve hyperlipidaemia- if persistent treat with statins. Avoid prolonged bed-rest- give prophylactic anticoagulation if:
immobile & if serum albumin is ↓ & proteinuria is within nephrotic range. Treat HTN if proteinuria is ↑. Ace-I or ARA
should be used 1st line. Address other risk factors such as smoking, exercise and diet. Renal vein thrombosis: can occur
in nephrotic syndrome due to hypercoagulable state. Other causes: invasion by renal cell cancer, thrombophilia. Signs:
often asymptomatic, may be present with loin pain, haematuria, palpable kidneys, sudden deterioration in renal
function, PE. Diagnosis: dopplar US, CT, MRI, renal angiography. Px: anticoagulate with warfarin for 3-6months if no CI.
Bladder cancer
 Bladder cancer

Male: female 4:1. Grade 1= differentiated grade 2= intermediate grade 3= poorly differentiated. 80% confined to
bladder mucosa, only ~20% penetrate muscle. Presentation: painless haematuria, recurrent UTIs; voiding irritability.
Associations: smoking; aromatic amines (rubber industry); chronic cystitis; schistosomiasis (infection caused by
parasites); pelvic irradiation. Tests: urine: microscopy/cytology (cancers may cause sterile pyuria), IVU may show filling
defects +/- ureteric involvement, cystoscopy EUA helps assess spread, CT/MRI/lymphangiography may show involved
pelvic nodes. Staging: Tis= carcinoma in situ: not felt at EUA, Ta= tumour confined to epithelium: not felt at EUA, T1=
tumour in lamina propria: not felt at EUA, T2= Superficial muscle involved: rubbery thickening at EUA, T3= deep muscle
involved: EUA: mobile mass, T4= invasion beyond bladder: fixed mass at EUA. Treatment: Tis/Ta/T1(80% of pts)
Diathermy (production of heat to destroy tissue) via transurethral cystoscopy/resection of bladder (TURBT). Consider
intra-vesical chemotherapeutic agents (e.g. mitomycin C) for multiple small/high grade tumours. Immunotherapy
with intra-vesical BCG is useful in high-grade tumours & carcinoma in-situ & may be better at preventing tumour
progression than mytomycin C in superficial disease. 5Yr survival= 95%. T2-3: radical cystectomy (removal of bladder) is
gold standard. Radio gives worse 5yr prognosis than surgery but preserves bladder. ‘salvage’ cystectomy can be
performed if radio fails but worse results than primary surgery. Post-op chemo is toxic but effective & may also be role
for neoadjuvant chemotherapy. If bladder neck not involved then orthotopic reconstruction rather than forming
urostoma is an option but adequate tumour clearance must not be compromised. T4: usually palliative radio/chemo.
Chronic catherterization & urinary diversions may help to relieve pain. Follow-up: history, exam & regular cystoscopy.
High-risk tumours: every 3m for 2yrs then 6m. Low risk tumours: every 9m then per yr. Tumour spread: local -> pelvic
structures; lymphatic -> iliac & para-aortic nodes; haematogenous -> liver & lungs. Survival: depends on age at surgery.
3yr survival after cystectomy for T2 & T3 tumours is 60% if 65-75yo, falling to 40% if 75-82yo. Unilateral pelvic node
involvement: only 6% of pts survive 5yrs. 3yr survival with bilateral/para-aortic node involvement is nil. Complications:
cystectomy can result in urinary/sexual malfunction. Massive bladder haemorrhage may complicate treatment;
consider alum solution bladder irrigation- an outpatient procedure.
 Biochem- some major disease patterns

Dehydration: ↑urea, ↑albumin, ↑haematocrit (volume %RBC’s in blood), also ↓urine volume and ↓skin
turgor. Abnormal kidney function: Low GFR: ↑urea, ↑creatinine, ↑K+, ↑H+, ↑urate, ↑PO4, ↑anion gap,
↓Ca2+, HCO3 ↓ oliguria. Causes: early acute oliguric renal failure, CKD (chronic kidney disease), in CDK also=
↓Hb, ↑PTH & renal bone disease. Tubular dysfunction: ↓K+, ↓urate, ↓PO4, HCO3 ↓, ↑H+, normal urea &
creatinine. Other possible findings inc polyuria with urinary glucose, amino acids, proteins/phosphate. Diagnosis
made by testing renal concentrating ability. Causes: recovery from acute renal failure, hypercalcaemia,
hyperuricaemia, myeloma, pyelonephritis, hypokalaemia, Wilson’s disease, galactosaemia & heavy metal
poisoning. Thiazide & loop diuretics: ↑HCO3, ↑urea, ↓Na+, K+ ↓. Hepatocellular disease: ↓albumin,
↑bilirubin, ↑AST, alk phos ↑ slightly, ↑clotting times. Cholestasis: ↑bilirubin, ↑ ↑gammta-GT, ↑ ↑alk phos,
↑AST. Excess alcohol intake: evidence of hepatocellular disease. Early evidence in gamma-GT ↑, ↑MCV &
ethanol in blood before lunch. MI: ↑troponin, ↑CK, ↑AST, ↑LDH. Addison’s disease: ↑K+ ↑, ↓Na+. Cushing’s
syndrome: ↓K+, ↑HCO3, ↑Na+. Conn’s syndrome: may show ↑HCO3, ↓K+. Na+ normal/ ↑(HTN). DM:
↑glucose (↓HCO3 if acidotic). Diabetes insipidus: ↑Na+, ↑plasma osmolality, ↓urine osmolality.
Inappropriate ADH secretion (SIADH): ↓Na+ with normal/ ↓urea & creatinine, ↓plasma osmolality. ↑urine
osmolality, ↑urine Na+. Some immunodeficiency states: normal serum albumin but low total protein (because
IG’s missing).
Biochem- some major disease patterns continued…

• In osteoporosis everything is normal.

Ca2+ PO4 Alk Phos

Osteomalacia ↓ ↓ ↑

Paget’s normal normal ↑↑

Myeloma ↑ ↑, normal Normal

Bone metastases ↑ ↑, normal ↑

1degree ↑ ↓ ↑, normal
hyperparathyroidism

Hypoparathyroidism ↓ ↑ normal

Renal failure (Low GFR) ↓ ↑ ↑, normal

Metabolic acidosis (pH ↓, HCO3 ↓) & increased anion gap: lactic acid, urate
(renal failure), ketones (DM, alcohol), drugs/toxins. Metabolic acidosis & normal
anion gap: renal tubular acidosis, diarrhoea, drugs, Addison’s disease, pancreatic
fistula, ammonium chloride ingestion.
Metabolic alkalosis (pH ↑ , HCO3 ↑ ): Vomiting, K+ depletion (diuretics), burns
& ingestion of base.
Resp acidosis: (CO2 ↑, pH ↓): Type 2 resp failure due to any lung,
neuromuscular or physical cause. Most commonly chronic obstructive pulmonary
disease (COPD). Look at Pa02- probs be low- O2 therapy required?- use
controlled O2 as too much can make matters worse. Beware exhaustion in
asthma, pneumonia & pulmonary oedema, which can present with this picture
when close to resp arrest- pts require urgent ITU review for ventilator support.
Resp alkalosis (CO2 ↓, pH ↑) : result of hyperventilation. CNS causes: stroke,
subarachnoid bleed, meningitis. Others: Anxiety, altitude, T ↑, pregnancy, PE,
drugs e.g. salicylates.
Hypernatremia
 Hypernatraemia

Signs & symptoms: lethargy, thirst, weakness, irritability, confusion, coma and fits
along with signs of dehydration. Lab features: ↑Na+, ↑PCV, ↑alb, ↑urea.
Causes: usually due to water loss in excess of Na+ loss. Fluid loss without water
replacement (e.g. diarrhoea, vomit, burns). Incorrect IV fluid replacement
(excessive saline). Diabetes insipidus. Suspect if large urine volume- may follow
head injury/CNS surgery esp pituratory. Osmotic diuresis (for diabetic coma).
Primary aldosteronism: suspect if ↑BP, K+ ↓, alkalosis (HCO3 ↑). Management:
give water orally if possible. If not, given IV dextrose slowly, guided by urine
output & plasma Na+. Use IV saline if hypovolemic since it causes less marked
fluid shifts & is hypotonic in a hypertonic pt. avoid hypertonic solutions.
Hyponatremia
 Hyponatraemia

Plasma Na+ conc. Depends on amount of both Na+ & water in plasma- so disease doesn’t necessarily imply Na+
depletion.
Signs & symptoms: look for anorexia, nausea & malaise initially followed by headache, irritability, confusion,
weakness, ↓GCS & seizures- depending on severity and rate of change in serum Na+. Cardiac failure/oedema
may help to indicate cause. Hyponatraemia also increases risk of falls in elderly.
Causes: if pt dehydrated AND urinary Na>20mmol then (Na+ & H2O los via kidneys) : Addison’s, renal failure,
diuretic excess & osmolar diuresis (↑glucose, ↑urea) if Na<20mmol: (Na+ & H20 are lost other then via kidneys):
diarrhoea, vomiting, fistulae, burns, rectal villous adenoma, small bowel obstruction, trauma, CF, heat exposure.
If pt oedematous then: nephrotic syndrome, cardiac failure, liver cirrhosis (hyponatremia may precede oedema),
renal failure. If pt not oedematous and urine osmolality >500mmol then: SIADH, if <500mmol: water overload,
severe hypothyroidism, gluco-corticoid insufficiency. Artefactual causes: blood sample was from a drip arm; high
serum lipid/protein content causing ↑serum volume, with ↓Na+ conc. But normal plasma osmolality. If
hyperglycaemic add some Na+ slowly. Iatrogenic hyponatraemia: if dextrose is infused continuously without
adding saline, the dextrose is quickly used rendering fluid hypotonic & causing hyponatraemia. Those esp at risk:
pt on thiazide diuretics, women (pre-meno), those undergoing physiological stress (e.g. post-operative, septic). In
some pts, only marginally low plasma Na+ levels cause serious effects. Management: correct underlining cause-
never base treatment on Na+ conc alone. Replace Na+ and water at same rate as they were lost. In asymptomatic
chronic hyponatraemia: fluid restriction is often sufficient if asymptomatic, although demeclocycline (ADH
antagonist) may be required. If hypervolaemic (cirrhosis, CCF) treat underlining disorder first. In acute
symptomatic hyponatraemia/dehydrated, cautious rehydration with saline may be given- do not correct rapidly as
central pontine mylinolysis may result. Consider furosemide when not hypovolaemic to avoid fluid overload.
 Hyponatraemia continued…

Management: vasoporessor receptor antagonists: ‘vaptans’ promote water

excretion without loss of electrolytes & appear to be effective in treating
hypervolaemic & euvolaemic hyponatraemia. In emergency (seizures, coma) seek
expert help. Consider hypertonic saline +/- furosemide. Aim for gradual increase in
Na+. Beware heart failure & central pontine myelonolysis.
 SIADH

Flow chart shows normal cycle but SIADH lacks neg feedback.
 SIA DH

An important but over-diagnosed cause of hyponatraemia. Diagnosis requires

conc. Urine (Na+ >20mmol and osmolality >500mosmol) in presence of
hyponatraemia (Na+ <125mmol) or low plasma osmolality & absence of
hypovolaemia, oedema or diuretics.
Causes: maliginancy: lung small-cell, pancreas, prostate, thymus or lymphoma.
CNS disorders: meningoencephalitis, abscess, stroke, subarachnoid or subdural
haemorrhage, head injury, neurosurgery, Guillain-Barre, vasculitis or SLE. Chest
disease: TB, pneumonia, abscess, aspergillosis. Endocrine disease:
hypothyroidism. Drugs: opiates, psychotropics, SSRIs, cytotoxics. Other: acute
intermittent porphyria, trauma, major abdominal or thoracic surgery,
symptomatic HIV.
Treatment: treat cause & restrict fluid. Consider salt +/- loop diuretic if severe.
Vasopressin receptor antagonists (‘vaptans’) are an emerging class of drug used
in SIADH & other types of hyponatraemia.
Hyperkalaemia
 Hyperkalaemia

Plasma K+ >6.5mmol is an emergency & needs urgent treatment. Worry is

Myocardial hyper-excitability leading to VF & cardiac arrest. First attend pt- do they
look unwell? If not, could it be an artefactual result? Concerning signs &
symptoms: inc a fast irregular pulse, chest pain, weakness, palpations & light-
headedness. ECG: tall tented T wave, small P waves, wide QRS complex and VF.
Artefactual results: if pt is well & has none of above findings, repeat test urgently
as it may be artefactual, caused by: haemolysis (difficult venepuncture, pt clenched
fist); contamination with potassium EDTA anticoagulant in FBC bottles (do FBCs
after U&E); thrombocythaemia (K+ leaks out of platelets during clotting); delayed
analysis (K+ leaks out of RBCs- particular problems in primary care due to long
transit to lab). Causes: oliguric renal failure, K+ sparing diuretics, Rhabdomyolysis,
Metabolic acidosis, excess k+ therapy, Addison’s disease, massive blood
transfusion, burns, drugs e.g. ACE-I, suxamethonium, artefactual result. Treatment
in non-urgent cases: treat underlining cause. Polystyrene sulfonate resin (calcium
resonium) binds K+ in gut preventing absorption & bringing K+ levels down over a
few days. If vomiting prevents PO give enema followed at 9h by colonic irrigation.
H yp oka lae mia
 H ypo kal aem ia

If K+ <2.5mmol, urgent treatment required. Hypokalaemia exarcebates digoxin

toxicity. Signs & symptoms: muscle weakness, hypotonia, hyporeflexia, cramps,
tetany, palpations, light-headedness (arrhythmias). ECG: small/inverted T waves,
prominent U waves (after T wave), long PR interval & depressed ST segments.
Causes: diuretics, vomiting & diarrhoea, pyloric stenosis, rectal villous adenoma,
intestinal fistula, cushing’s syndrome/steroids/ACTH, Conn’s syndrome, Alkalosis,
purgative & liquorice abuse, renal tubular failure. If on diuretics, ↑HCO3 best
indication that hypokalaemia is likely to have been long standing. Mg2+ may be
low, & hypokalaemia is often difficult to correct until Mg2+ levels are normalised.
Suspect Conn’s syndrome if hypertensive, hypokalaemic alkalosis in someone not
taking diuretics. In hypokalaemic periodic paralysis, intermittent weakness
lasting up-to 72h appears to be caused by K+ shifting from extra-intracellular
fluid. Treatment: if mild: give oral K+ supplement. If taking a thiazide diuretic,
hypokalaemia rarely needs treating. If severe: give IV potassium cautiously. Do
give K+ if oliguric. Never give K+ as fast stat bolus dose.
Hypercalcaemia
 Hypercalcaemia

Signs & symptoms: ‘bones, stones, groans and psychic moans’. Abdominal pain; vomiting; constipation; polyuria;
depression; anorexia; weight loss; tiredness; weakness; hypertension; confusion; pyrexia; renal stones; renal
failure; ectopic calcification; cardiac arrest. ECG: QT interval ↓. Causes: most commonly malignancy (e.g. from
bone metastases, myeloma, PTHrP) or primary hyperparathyroidism. Others: sarcoidosis, vit D, intoxication,
thyrotoxicosis, lithium, tertiary hyperparathyroidism, milk-alkali syndrome & familial benign hypocalciuric
hypercalcaemia. Investigations: main distinction is malignancy VS 1degree hyperparathyroidism. Pointers to
malignancy: ↓albumin, ↓CL-, alkalosis, ↓K+, ↑PO4, ↑alk phos. ↑PTH indicates hyperparathyroidism. Also FBC,
protein electrophoresis, CXR, istope bone scan, 24h urinary Ca2+ excretion.
Treatment: correct dehydration if present with IV saline. Bisphosphonates prevent bone resorption by inhibiting
osteoclast activity, single dose pamidronate lowers Ca2+ over 2-3d; max effect is at 1wk- infuse slowly. SE: fly
symptoms, PO4 ↓, bone pain, myalgia, nausea, vomiting, headache, lymphocytopenia, ↓Mg2+, Ca2+, seizures.
Further management: chemo may help malignancy. Steroids used in sarcoidosis e.g. prednisolone. Furosemide
should only be used once fully rehydrated & with concomitant IV fluids- avoid thiazides.
Hypocalcaemia
 Hypocalcaemia

Signs & symptoms: mild: cramps, perioral numbness/paraesthesiae. Severe:

carpopedal spasm (esp if brachial artery compressed, trousseau’s sign- wrist &
fingers flex and draw together); laryngospasm, seizures. NM excitability may also
be demonstrated by tapping over parotid (facial nerve) causing facial muscles to
twitch (Chvostek’s sign). Cataract if chronic hypocalcaemia. ECG: long QT interval.
Remember SPASMODIC: spasms. perioral paraesthesiae.
Anxious/irritable/irrational, Seizures, Muscle tone ↑in smooth muscle hence
colic, wheeze & dysphagia. Orientation impaired (time, place, person) &
confusion. Dermatitis (e.g. atopic/exfoliative). Impetigo herpetiformis. Chvostek’s
sign; choreoathetosis; cataract; cardiomyopathy (long QT interval on ECG).
Causes: With ↑PO4: chronic kidney disease, hypoparathyroidism/parathyroid
surgery, pseudohypoparathyroidism, acute rhabdomyolysis, Vit D deficiency,
hypomagnesaemia. With normal/ ↓ PO4: osteomalacia, acute pancreatitis, over-
hydration, resp alkalosis. Treatment: mild symptoms: give Ca2+ with daily Ca2+
levels. Chronic kidney disease: may require alfacalcidol. Severe: IV calcium
gluconate.
Urate renal stones
 Urate & kidney

Causes of hyperuricaemia: high levels of urate in blood may result from increased turnover (15%) or
reduced excretion of urate (85%). Either may be drug induced. Drugs: cytotoxics, thiazides, loop diuretics,
pyrazinamide. Increased cell turnover: lymphoma, leukaemia, psoriasis, haemolysis, muscle death. Reduced
excretion: primary gout, CKD, lead nephropathy, hyperparathyroidism, pre-eclampsia. Other:
hyperuricaemia may be associated with HTN & hyperlipidaemia. Urate may be raised in disorders of purine
synthesis such as Lesch-Nyhon syndrome. Hyperuricaemia & renal failure: how urate causes renal failure:
urate is poorly soluble in water so over excretion leads to precipitation. Renal failure occurs most commonly
because urate precipitates in renal tubules. In some instances ureteric obstruction from urate crystals may
occur. This responds to retrograde ureteric catheterisation & lavage. Prevention of renal failure: before
starting chemo, ensure good hydration & initiate allopurinol/rasburicase which prevent a sharp rise in urate
following chemo- remote risk of xanthine nephropathy. Treatment of hyperuricaemic acute renal failure:
exclude bilateral ureteric obstruction then give prompt rehydration +/- loop diuretic to wash uric acid
crystals out of renal tubules & correct electrolyte abnormalities. Once oliguria is established, haemodialysis
is required. Gout. Urate renal stones: comprise 5-10% of all renal stones & are radiolucent. Incidence: ~5-
10% in temperate climates but up-to 40% in hot, arid climates. Male: female 4:1- most have no detectable
abnormalities in urate metabolism. Risk factors: acidic/strongly conc. Urine; ↑urinary excretion of urate;
chronic diarrhoea; distal small bowel disease or resection; ileostomy; obesity; DM; chemo for
myeloproliferative disorders; inadequate caloric/fluid intake. Treatment: hydration to ↑urine volume.
Unlike most other renal calculi, existing uric acid stones can often be dissolved with either systemic or
topical alkalinizing agents. Potassium citrate or potassium bicarbonate at a dose titrated to alkalinize urine
to pH of 6-7 dissolves some urate stones. If hyperuricosuria, consider dietary management +/- allopurinol.
 Osteomalacia

Top mid pic shows a transilial bone biopsy in a patient with osteomalacia demonstrating unmineralised osteoid
 Osteomalacia

Top left pic shows AP view of the pelvis shows typical pseudofractures (circular bits)
associated with Osteomalacia. Top right shows tumour induced Osteomalacia.
 Os teo ma lac ia

In osteomalacia there is normal amount of bone but its mineral content is low. This is the reverse of osteoporosis in
which mineralisation is unchanged, but there is overall bone mass loss. Rickets is result if process occurs during period
of bone growth; osteomalacia is result if it occurs after fusion of epiphyses. Signs & symptoms: rickets: growth
retardation, hypotonia, apathy in infants. Once walking: knock-kneed, bow-legged & deformities of metaphyseal-
epiphyseal junction. Features of ↓Ca2+ often mild. Children with rickets are ill. Osteomalacia: bone pain &
tenderness; fractures (esp femoral neck); proximal myopathy (waddling gait), due to PO4 ↓ & vit D deficiency. Causes:
Vit D deficiency: due to malabsorption, poor diet, lack of sunlight. Renal osteodystrophy: renal failure leads to 1,25-
dihydroxy-cholecalciferol deficiency. Drug-induced: anticonvulsants may induce liver enzymes, leading to an increased
break-down of 25-hydroxyl-Vit D. liver disease: due to reduced hydroxylation of Vit D to 25-hydroxyl-cholecalciferol &
malabsorption of Vit D e.g. in cirrhosis. Tumour-induced osteomalacia: mediated by raised tumour production of
phosphatonin fibroblast growth factor 23 which causes hyperphosphaturia. ↓serum PO4 often causes myalgia &
weakness. Investigations: plasma: Mildly Ca2+ ↓; PO4; alk phos ↑; PTH high; 25(OH)-vit D ↓, except in Vit D
resistance. In renal failure 1,25(OH)2-Vit D ↓. Biopsy: bone biopsy shows incomplete mineralisation. Muscle biopsy is
normal. X-RAY: loss of cortical bone; also, apparent partial fractures without displacement may be seen esp on lateral
border of scapula, inferior femoral neck & medial femoral shaft. Cupped, ragged metaphyseal surfaces seen in rickets.
Treatment: in dietary insufficiency, give Vit D e.g. as calcium D3 forte tablet. In malabsorption or hepatic disease give
Vit D2 or parenteral calcitrol. If due to renal disease or Vit D resistance give alfacalcidol or calcitrol & adjust dose
according to plasma Ca2+ -> both can cause danger hypercalcaemia. Monitor plasma Ca2+ weekly & if
vomiting/nausea. Vit D-resistant rickets: exists in 2 forms. Type I has low renal 1alpha-hydroxylase activity, & type 2
has end-organ resistance to 1,25-dihydroxy-Vit D3, due to a point mutation in receptor- both treated with large doses
of calcitrol. X-linked hypophosphataemic rickets: dominantly inherited due to defect on renal phosphate handling.
Rickets develops in early in childhood & is associated with poor growth. Plasma PO4 is low, alk phos is high & there is
phosphaturia. Treatment is with high doses of oral phosphate & calcitrol.
 Paget’s disease of bone

• Top left pic shows bone in lytic phase. Paget’s disease of bone - a chronic bone disorder characterised by excessive abnormal bone remodelling. There are three disease
phases; the ‘lytic’ phase predominated by osteoclastic activity, the ‘mixed phase’ with osteoblastic as well as osteoclastic activity, and the ‘sclerotic phase’ or late phase.
• Case A in top right pic - shows typical late phase Paget’s of the proximal femur with cortical thickening and coarsened trabeculations. This patient also has advanced hip
joint osteoarthritis with flattening of the femoral head secondary to bone softening. 
 Paget’s disease of bone

Also called osteitis deforman’s, there is increased bone turnover associated with
increased numbers of osteoblasts & osteoclasts with resultant remodelling, bone
enlargement, deformity and weakness. Rare in under 40s. Incidence rises rises
with age. Commoner in temperate climates & in anglo-Saxons.
Clinical features: asymptomatic in ~70%. Deep, boring pain & bony deformity &
enlargement- typically in pelvis, lumbar spine, skull, femur and tibia.
Complications inc: pathological fractures, osteoarthritis, ↑Ca2+, nerve
compression due to bone overgrowth, high-output CCF and osteosarcoma
(suspect if sudden onset or worsening of bone pain). Radio X-RAY: localised
enlargement of bone. Patchy cortical thickening with sclerosis, osteolysis, and
deformity. Affinity for axial skeleton, long bones & skull. Bone scan may reveal
‘hot spots’. Blood biochem: Ca2+ and PO4 normal, alk phos markedly raised.
Treatment: If analgesia fails, alendronate may be tried to reduce pain and/or
deformity.
 Pla s ma e nzy me s

Alkaline phosphatase: liver disease (suggests cholestasis (bile cannot flow from
liver to duodenum), cirrhosis, abscess, hepatitis or malignancy). Bone disease,
esp Paget’s disease, growing children, healing fractures, bone metastases,
osteomalacia, osteomyelitis, CKD & hyperparathyroidism. Congestive cardiac
failure (moderately raised alk phos), pregnancy (placenta makes own isoenzyme).
Alanine & aspartate aminotransferase (ALT and AST): liver disease (suggests
hepatocyte damage), AST also ↑MI, skeletal muscle damage (esp crush injuries)
& haemolysis. Alpha-Amylase: acute pancreatitis (smaller rise in chronic
pancreatitis as less tissue remaining), also: severe uraemia, diabetic ketoacidosis,
severe gastroenteritis & peptic ulcer. Creatine kinase (CK): MI, muscle damage.
Gamma-glutamyl transferase (GGT, gamma GT): liver disease. Lactate
dehydrogenase (LDH): MI, liver disease, haemolysis- PE & tumour necrosis.
Troponin: MI, pericarditis, myocarditis, PE, sepsis, CPR. CKD.
 Hyperlipidaemia

4 classes: chylomicrons and VLDL (mainly triglyceride), LDL (mainly cholesterol), and HDL
(mainly phospholipid). Who to screen for hyperlipidaemia: those at risk: family history,
corneal arcus, <50yo, Xanthomata/Xanthelasmata. Those at risk of CVD: Known CVD, family
history <65yo, DM, HTN, smoker, ↑BMI, low socioeconomic/Indian Asian background. Types
of hyperlipidaemia: common primary hyperlipidaemia: accounts for 70% of hyperlipidaemia.
↑LDL only. Familial primary hyperlipidaemia: comprise multiple phenotypes. Risk of CVD ↑
↑. Secondary hyperlipidaemia: may be caused by cushing’s syndrome, hypothyroidism,
nephrotic syndrome or cholestasis. ↑LDL. Treat cause first. Mixed hyperlipidaemia: results in
↑LDL & triglycerides. Caused by type 2 DM, metabolic syndrome, alcohol abuse & CKF.
Management: lifestyle advice, e.g. diet and exercise. 1st line therapy: statins e.g. simvastatin,
↓cholesterol synthesis in liver, CI: porphyria, cholestasis, pregnancy. SE: myalgia +/- myositis,
ab pain and ↑LFTs. Cytochrome P450 inhibitors ↑serum conc.’s . 2nd line therapy: fibrates,
useful in mixed hyperlipidaemia or cholesterol absorption inhibitors e.g. ezetimibe; anion
exchange resins e.g. colestyramine; also consider nicotinic acid; SE: severe flushes, aspirin
helps this. Hypertriglyceridemia responds best to fibrates, nicotinic acid or fish oil.
Xanthomata: these yellow deposits may be eruptive, tuberous (plaques on elbows and knees)
or planar- also called palmar (orange streaks in palmar creases); ‘diagnostic’ of remnant
hyperlipidaemia or in tendons, eyelids (xanthelasma, or cornea (arcus) ).
 The porphyria’s

Top left shows hereditary coproporphyria. Top right shows porphyria. Bottom pics show variegate porphyria.
 The porphyria's

A heterogeneous group of rare diseases caused by various errors of haem biosynthesis which may genetic/acquired. Porphyrin
precursors are neurotoxic, while porphyrins themselves induce photosensitivity & formation of toxic free radicals. Alcohol, lead
and iron-deficiency cause abnormal porphyrin metabolism. Genetic counselling should be offered to all pts & their families.
Acute intermittent porphyria A low-penetrant autosomal dominant condition; 28% have no family history~10% of those with
defective gene have neurovisceral symptoms. Attacks are intermittent, more common in women and those aged 18-40- may be
precipitated by drugs. Urine porphobilinogens are raised during attacks (urine may go deep red on standing) & also in ~50%,
between attacks. Faecal porphyrin levels are normal. Never cutaneous photosensitivity. Also commonest form of porphyria.
Variegate porphyria & hereditary coproporphyria: autosomal dominant, characterized by photosensitive blistering skin lesions
and/or acute attacks. Former is prevalent in Afrikaners in south Africa. Porphobilinogen is high only during an attack, and other
metabolites may be detected in faeces. Triggers of an acute attack: infection, starvating, reproductive hormones, smoking,
anaesthesia, & cytochrome P450 inducers. Features of an acute attack: features of an acute attack: GI, ab pain, vomiting and
constipation. Neuropsychiatric: peripheral neuropathy (weakness, hypotonia, pain, numbness) seizures (often associated with
severe ↓Na+), psychosis. Cardiovascular: HTN, tachycardia, shock (due to sympathetic over-activity). Other: fever, ↓Na+, ↓K+,
proteinuria, urinary porphobilinogens, discoloured urine. Rare but serious complications inc bulbar & resp paralysis. -> beware
‘acute ab’ in acute intermittent porphyria: colic, vomiting, fever and ↑WCC- so mimicking an acute surgical ab- anaesthesia
could be disasterous. Treatment of an acute attack: remove precipitants, IV fluids to correct imbalance, high carb intake by NG
tube/IV if needed, IV haematin is 1st line (inhibits production of porphyrinogen precursors), nausea controlled with
prochlorperazine, sedate if necessary with chloropromazine, pain control with opiate/opioid analgesia, seizures can be
controlled with diazepam (although it will prolong attack), treat tachycardia and HTN with B-blocker. Non-acute porphyria's:
Porphyria cutanea tarda (PCT), erythropoietic protoporphyria & congenital erythropoietic porphyria are characterized by
cutaneous photosensitivity alone, as there is no overproduction of porphyrinogen precursors, only porphyrin’s. PCT presents in
adults with blistering skin lesions +/- facial hypertrichosis & hyperpigmentation. Total plasma porphyrin’s & LFTs are ↑. Screen
for associated disorders: hep C, HIV, iron overload, hepatocellular CA. Px: phlebotomy, iron chelators, chloroquine, sunscreens.
 Benign prostatic hypertrophy

Images on top right show enlarged prostate in US. Bottom left shows enlarged prostate (2 testicle balls things) on CT. bottom right shows histology of irregular acini (balls).
Common, 24% if aged 40-64; 40% if older. Pathology: benign nodular or diffuse proliferation of
musculofibrous & glandular layers of prostate. Inner (transitional) zone enlarges in contrast to
peripheral layer expansion seen in prostate carcinoma. Features: lower urinary tract symptoms (LUTS)
= nocturia, frequency, urgency, post-micturition dribbling, poor stream/flow, hesitancy, overflow
incontinence, haematuria, bladder stones, UTI. Management: assess severity of symptoms & impact
on life. PR exam. Tests: MSU; U&E, US. ‘rule-out’ cancer: PSA, trans-rectal USS +/- biopsy. Lifestyle:
Avoid caffeine, alcohol (to ↓urgency/nocturia). Relax when voiding. Void 2x in a row to aid emptying.
Control urgency by practising distraction methods e.g. breathing exercises. Train bladder by ‘holding
on’ to ↑time between voiding. Drugs: useful in mild disease & while waiting for surgery. Alpha-
blockers are 1st line e.g. tamsulosin, ↓smooth muscle tone (prostate & bladder), SE: drowsiness,
depression, dizziness, BP ↓, dry mouth, ejaculatory failure, extra-pyramidal signs, nasal congestion
weight ↑. 5Alpha-reductase inhibitors can be added/used alone e.g. finasteride (↓testosterones
conversion to dihydrotestosterone)- excreted in semen so warn to use condoms; females should avoid
handling- SE: impotence, ↓libido- effects on prostate size are &limited and slow. Surgery:
transurethral resection of prostate: (TURP) <14% become impotent- beware of bleeding, clot retention
and TUR syndrome: absorption of washout causing hyponatraemia and fits~20% need redoing within
10yrs. Transurethral incision of prostate: (TUIP) involves less destruction than TURP, less risk to sexual
function but gives similar benefit- achieves this by relieving pressure on urethra- perhaps best surgical
option for those with small glands. Retro-pubic prostatectomy is an open operation (if prostate v
large). Transurethral laser-induced prostatectomy (TULIP) maybe as good as TURP.
Melanoma
 melanoma

Female: male 1.3:1- commonly affects younger pts- early diagnosis vital. Short
periods of intensive UV exposure is major cause esp in early years. May occur in
pre-existing moles. If smooth, well demarcated & regular, it is unlikely to be
melanoma but diagnosis can be tricky, refer if >3points on Glasgow scale or with
1 with suspicious. ABCDE for diagnosis of melanoma= Asymmetry, Border-
irregular, Colour- non-uniform, diameter >7mm, Elevation. 1point each:
inflammation/crusting/bleeding, sensory change, diameter >7mm. 2point’s each:
change in size, shape, colour. Superficial spreading melanomas (70%) grow
slowly, metastasize later & have better prognosis than nodular melanomas (10-
15%) which invade deeply & metastasize early. Nodular lesions may be
amelanotic in ~5%. Others: Acral melanomas occur on palms, soles and
sublingual areas (equal frequency among black & white pts); lentigo maligna
melanoma evolves from pre-existing lentigo maligna. Breslow thickness, tumour
stage and presence of ulceration are important prognostic factors. Px: urgent
excision can be curative. Chemo give a response in 10-30% with metastatic
disease.
Hirsutism
 Hirsutism

Common (10% of women) & usually benign. Causes: familial, idiopathic,

↑androgen secretion by ovary (PCOS), ovarian cancer, adrenal cancer, cushings
syndrome, drugs (steroids). PCOS causes secondary oligo- or amenorrhoea,
infertility, obesity, acne and hirsutism. US: bilateral polycystic ovaries. Blood tests:
↑testosterone, ↓sex-hormone binding globulin, ↑LH:FSH ratio, TSH, lipids.
Metformin may restore cycles & fertility & helps insulin resistance (consider
OGTT). Management: local measures: shaving, laser photo-epilation, wax creams
e.g. eflornithine or electrolysis (expensive/time-consuming, but effective); bleach
(1:10 hydrogen peroxide). Oestrogens may help, consider combined pill- Yasmin
as its progesterone, drospirenone, is an antimineralocorticoid. If no real help
after 6-8m try co-cyprindiol, SE: depression. Metformin & spironolactone are
sometimes tried. Eating healthy is important. Clomifene is used for infertility.
Burns
 Burns

Resus & arrange transfer for all major burns. Assess site, size and depth of burn. Referral is still warranted in
cases of full thickness burns >5%, partial thickness burns >10% in adults or >5% in children or the elderly, burns
of special sites, chemical & electrical burns & burns with inhalational injury. Assessment: burn size is important
to assess as it influences the size of inflammatory response and thus fluid shift from intravascular volume.
Ignore erythema. Burn depth determines healing time/scarring; assessing this can be hard, even for the
experienced. The big distinction is whether the burn is partial thickness (painful, red and blistered) or full
thickness (insensate/painless; grey-white). NB: burns can evolve, particularly over first 48h. Resus: airway:
beware of upper airway obstruction developing if hot gases inhaled. Suspect if history of fire in enclosed space,
soot in oral/nasal cavity, singed nasal hairs/hoarse voice. Flexible laryngo/bronchoscopy is useful. Involve
anaesthetist early & consider early intubation. Obstruction can develop in first 24h. Breathing: exclude life-
threatening chest injuries (e.g. tension pneumothorax) & constricting burns- consider escharotomy (surgical
procedure to treat full thickness burns) if chest burns are impairing thorax excursion. Give 100% O2. suspect
CO poisoning from history, cherry-red skin & carboxyhaemoglobin level (COHb). With 100% O2. consider
hyperbaric 02 if: pregnant, CNS signs; >20% COHb. Treatment: ‘cool burn, warm pt’. Do not apply cold water
to extensive burns for long periods: may intensify shock. Take care with circumferential full thickness burns of
limbs as compartment syndrome may develop rapidly particularly after fluid resus. Decompress (escharotomy
& fasciotomy) as needed. If transferring to burns unit, do not burst blisters or apply any special as this can
hinder assessment. Simple saline gauze/paraffin gauze is suitable; cling film is useful as a temp measure &
relieves pain. Titrate morphine IV for good analgesia. Ensure tetanus immunity. Definitive dressings: there are
many dressings for partial thickness burns e.g. bio (pig/cadavar skin), synthetic and silver sulfadiazine cream
alone (flamazine) or with cerium nitrate as flammacerium; it forms a leathery eschar which resists infection.
Major full thickness burns benefit from early tangential excision & split-skin grafts as burn is major source of
inflammatory cytokines causing SIRS (systemic inflammatory response syndrome) & forms rich medium for
 G yn ae co mas tia

i.e abnormal amount of breast tissue in men; may occur in normal puberty.
Oestrogen/androgen ratio ↑. Causes: Hypogonadism, liver cirrhosis (oestrogen
↑), hyperthyroidism, tumours (oestrogen-producing e.g. testicular, adrenal; HCG-
producing, e.g. testicular, bronchial); Drugs: oestrogens, spironolactone, digoxin,
testosterone, marijuana, if stopping is impossible, consider testosterone if
hypogonadism +/- anti-oestrogen (tamoxifen).
 Rhe um at oid art hrit is

Bottom right pics (3) show synovitis in RA on an US

 Rheumatoid arthritis

RA is a chronic systemic inflammatory disease, characterized by a symmetrical , deforming, peripheral

polyarthritis. Epidemiology: prevalence is ~1% (↑in smokers). Female: male 2:1. peak onset: 5th-6th decade. HLA
DR4/DR1 linked (associated with ↑severity). Presentation: typically: symmetrical swollen, painful and stiff small
joints of hands and feet, worse in morning. This can fluctuate & larger joints may become involved. Less common
presentations: sudden onset, widespread arthritis; recurring mono/polyarthritis of various joints; persistent
monoarthritis (often knee, shoulder or hip); systemic illness with extra-articular symptoms e.g. fatigue, fever,
weight loss, pericarditis and pleurisy, but initially few joint problems (commoner in female); polymyalgic onset-
vague limb girdle aches; recurrent soft tissue problems (e.g. frozen shoulder, carpal tunnel synd, de Quervain’s
tenosynovitis). Signs: early (inflammation, no joint damage): swollen MCP, PIP, wrist, or MTP joints (often
symmetrical). Look for tenosynovitis or bursitis. Later (joint damage, deformity): ulnar deviation of fingers in
dorsal wrist subluxation. Boutonniere & swan-neck deformities of fingers or Z-deformity of thumbs occur. Hand
extensor tendons may rupture. Foot changes are similar. Larger joints can be involved. Atlanto-axial joint
subluxation may threaten spinal cord (rare). Extra-articular: nodules- elbows & lungs; lymphadenopathy;
vasculitis; fibrosing alveolitis. Obliterative bronchiolitis; pleural & pericardial effusion; Raynaud’s; carpal tunnel
synd; peripheral neuropathy; splenomegaly (5%); episceleritis, sceleritis, scleromalacia, keratoconjuctivitis sicca;
osteoporosis; amyloidosis. Investigations: Rheuamatoid factor (RhF) is +ve in ~70%. High titre is associated with
severe disease, erosions & extra-articular disease. Anti-cyclic citrullinated peptide antibodies (ACPA/anti-CCP) are
highly specific for RA. Often anaemia of chronic disease. Inflammation causes ↑platelets, ↑ESR, ↑CRP. X-RAY
show soft tissue swelling, juxta-articular osteopenia and ↓joint space. Later there may be bony erosions,
subluxation or complete carpal destruction. US and MRI can ID synovitis more accurately, & have greater
sensitivity in detecting bone erosions than conventional X-RAY’s.
 Rheumatoid arthritis continued….

Diagnostic criteria: scores >6/10 are diagnostic.

Joint involvement (swelling or tenderness +/- imaging evidence)
1 large joint= O 2-10 large joints= 1 1-3 small joints= 2
4-10 small joints= 3 >10joints (at least 1 small joint) = 5
Serology (at least 1 test result needed)
Neg RF & neg anti-CCP=0 Low +ve RF or low +ve anti-CCP= 2
High +ve RF or high +ve anti-CCP= 3
Acute phase reactants (at least 1 test result needed)
Normal CRP & ESR= 0 Abnormal CRP or ESR= 1
Duration of symptoms
<6 wks= 0 >6 wks= 1
 Rheumatoid arthritis continued…

Management: disease-modifying ant-rheumatic drugs (DMARDs) are 1st line for treating RA & should
ideally be started within 3m of persistent symptoms- can take 6-12w for symptomatic benefit- best results
achieved with combo of methotrexate, sulfasalazine & hydroxychloroquinine. Immunosuppression is a
potential fatal SE of treatment esp in combo with methotrexate which can result in pancytopenia (deficit
of all 3 components of blood- red & white cells and platelets), ↑susceptibility to infection & neutropenic
sepsis- regular FBC monitoring required. Other SE: methotrexate- pneumonitis, oral ulcers, hepatotoxicity.
Sulfasalazine- rash, ↓sperm count, oral ulcers. Lefunomide- teratogenicity (male & female), oral ulcers,
↑BP, hepatotoxicity. Hydroxychloroquinine- irreversible retinopathy (request annual ophthalmology
review). Bio agents & NICE guidelines: 1) TNF-alpha inhibitors e.g. Infliximab, etanercept, adalimumab,
certolizumabpegol & golimumab. All approved by NICE as 1st line bio agents for active RA after failure to
respond to DMARDs & with a DAS28 >5.1. where methotrexate is CI, adalimumab & etanercept can be
used as monotherapy. Clinical response can be striking, with improved function & health outcomes,
although some pts may have inadequate or sustained response. 2) B cell depletion e.g. Rituximab used in
combo with methotrexate & approved by NICE for severe active RA where DMARDs & a TNF-alpha
blocker have failed. 3) IL-1 and IL-6 inhibition e.g. Tocilizumab (IL-6 blocker) in combo with methotrexate
for pts where both a TNF-alpha blocker & rituximab have failed or CI. 4) Disruption of T cell function e.g.
Abatacept- used infrequently for pts with severe active RA who have not responded to DMARDs & TNF-
alpha blocker or rituximab. SE of Bio agents: serious infection, inc reactivation of TB (screen & consider
prophylaxis) & hepatitis B; worsening heart failure; hypersensitivity; injection-site reactions & blood
disorders. Neutralising antibodies may ↓efficacy with infliximab & adalimumab; ANA & reversible SLE-
type illness evolve.
 Rheumatoid arthritis continued…

Management: disease activity measured using DAS28 aim to reduce score <3.
steroids may rapidly reduce symptoms & inflammation. Useful for treating acute
exacerbations (flares) e.g. IM depot methylprednisolone. Intra-articular steroids
have a rapid but short-term effects. Oral steroids (prednisolone) may control
difficult symptoms, but SE’s preclude routine long-term use. NSAIDs are good for
symptom relief but no effect on disease progression. Paracetamol & weak opiates
rarely effective. Offer specialist physio- occupational therapy e.g. aids and splints.
Surgery may relieve pain, improve function & prevent deformity. ↑risk of CVD and
cerebrovascular disease, as atherosclerosis is accelerated in RA. Manage risk
factors. Smoking ↑symptoms of RA.
 Vasculitis

Top right pic shows inflamed & dilated temporal in giant cell arteritis.
 vasculitis

An inflammatory disorder of blood vessels causing destruction/stenosis. Can affect vessels of any organs &
presentation depends on which organs are involved. May be a primary condition or secondary to other diseases e.g.
SLE, RA, hepatitis, B&C, HIV. Its categorized according to main size of blood vessels affected: large: giant cell arteritis,
Tawasaki disease Medium: Polyarteritis nodosa, Kawasaki disease Small: ANCA +ve vasculitis has a predilection for
resp tract & kidneys. It includes p-ANCA associated microscopic polyangiitis, glomerulonephritis & Churg-Strauss
syndrome and c-ANCA associated Wegner’s granulomatosis. ANCA –ve vasculitis Henoch- Schonlein purpura,
Goodpasture’s syndrome and cryoglobulinaemia. Symptoms: may only be overwhelming fatigue with ↑ESR/CRP.
Consider vasculitis in any un-ID multisystem disorder. If presentation doesn’t fit clinically/serologically into a specific
category consider maliginancy-associated vasculitis. Severe vasculitis flare is an emergency (e.g. critical renal failure
<24h). Tests: ESR/CRP ↑. ANCA may be +ve. ↑creatinine if renal failure. Urine: proteinuria, haematuria, casts on
microscopy. Angiography +/- biopsy may be diagnostic. Management: large-vessel vasculitis: steroids in most cases.
Medium/small: standard therapy is IV cyclophosphamide. Azathioprine may be useful as steroid-sparing
maintenance treatment. Giant cell arteritis (GCA)= cranial/temporal arteritis: common in elderly- consider
Takayasu’s if under 55yrs. Associated with PMR in 50%. Symptoms: headache, temporal artery & scalp tenderness,
jaw claudication, amaurosis fugax or sudden blindness typically in one eye. Extra-cranial symptoms may inc
dyspnoea, morning stiffness & unequal or weak pulses. -> if you suspect GCA do ESR & start prednisolone for 3d if
visual symptoms- ask an ophthalmologist. Tests: ESR & CRP ↑ ↑, platelets ↑, alk phos ↑, Hb ↓. Get temporal
artery biopsy within 7d of starting steroids. Skip lesions occur so don’t be put off by a neg biopsy (up to 10%).
Prognosis: typically a 2yr course, then complete remission. Reduce prednisolone once symptoms have resolved &
ESR ↓; ↑dose if symptoms recur. The main cause of death & morbidity in GCA is long-term steroid treatment so
consider risks & benefits! Give gastric & bone protection (PPI & bisphosphonates).
 Vasculitis continued…

Polyarteritis nodosa (PAN): PAN is necrotising vasculitis that causes aneurysms & thrombosis in medium sized
arteries leading to infarction of affected organs with severe systemic symptoms male: female 2:1. may be associated
with hepatitis B and is rare in UK. Symptoms: typically systemic features, plus predominantly skin (rash & ‘punched
out’ ulcers), renal (main cause of death, though glomerulonephritis is not seen), cardiac, GI & GU involvement.
Coronary symptoms occur in Kawasaki disease. Tests: often ↑WCC, mild eosinophilia (30%), anaemia, ↑ESR, ↑CRP,
ANCA –ve. Renal or mesenteric angiography, or renal biopsy can be diagnostic. Treatment: control BP meticulously.
Most respond to corticosteroids & cyclophosphamide. Hep B should be treated with antiviral after initial treatment
with steroids. Microscopic polyangiitis: a necrotising vasculitis affecting small & medium sized vessels. Symptoms:
rapidly progressive glomerulonephritis usually features; pulmonary haemorrhage occurs in up to 30%; other
features are rare. Tests: pANCA +ve. Treatment: as for pan.
Features of vasculitis: systemic: fever, malaise, weight loss, arthralgia, myalgia. Skin: purpura, ulcers, livedo
reticularis, nailbed infarcts, digital gangrene. Eyes: episceleritis, scleritis, visual loss. ENT: epiostaxis, nasal crusting,
stridor, deafness. Pulmonary: haemoptysis & dyspnoea (due to pulmonary haemorrhage). Cardiac: Angina/Mi
(coronary arteritis), HF & pericarditis. GI: pain/perforation (infarcted viscus), malabsorption (chronic ischaemia).
Renal: HTN, haematuria, proteinuria, casts, RF; glomerulonephritis in ANCA +ve vasculitis. Neuro: stroke, fits,
chorea, psychosis, confusion, impaired cognition, altered mood. Arteritis of vasa nervorum (arterial blood supply to
peripheral nerves) may cause mononeuritis multiplex or a sensorimotor polyneuropathy. GU: Orchitis- testicular
pain /tenderness.
Polymyalgia rheumatica
 Polymyalgia rheumatic (PMR)

PMR not true vasculitis & its pathogenesis is unknown. PMR and GCA share same
demographic characteristics and, although separate conditions, both frequently
occur together. Features: age>50yrs, sub-acute onset (<2w) of bilateral aching,
tenderness & morning stiffness in shoulders & proximal limb muscles +/- mild
polyarthritis, tenosynovitis, & carpal tunnel syndrome (10%). Weakness not a
feature. May be associated fever, fatigue, anorexia, depression and ↓weight.
Investigations: CRP ↑, ESR typically >40 (but may be normal); ALP is ↑ in 30%.
Note creatinine kinase levels are normal (helping to distinguish from
myositis/myopathies) differentials: recent onset RA, polymyositis, hypothyroidism,
primary muscle disease, occult malignancy/infection, osteoarthritis, neck lesions,
bilateral sub-acromial impingement. Management: Prednisolone. Expect a
dramatic response within a week & consider alternative diagnosis if not. ↓dose
slowly. Investigate apparent ‘flares’ during withdrawal- recurrent symptoms may
be attributable to another condition. Most need steroids for 2yrs>, so give gastric &
bone protection.
 Sarcoidosis

Top right CXR shows  bilateral coarse reticulations with architectural distortion, traction bronchiectasis, and upward retraction of both hila
(arrows) associated with calcified mediastinal and hilar nodes (arrowheads)- stage 4. bottom middle pic shows bilateral hilar lymphadenopathy.
sarcoidosis
 s a rco ido s is

Multisystem granulomatous disorder of unknown cause. Prevalence highest in northern Europe. Usually affects adults aged 20-
40yrs, more commonly in women. African-caribbeans affected more frequently & more severely than caucasions, particularly
but extra-thoracic disease. Associated with HLA-DRB1 & DQB1 alleles. Clinical features: in 20-40% disease discovered
incidentally, after a routine CXR & thus is asymptomatic. Acute sarcoidosis often presents with erythema nodosum +/-
polyarthralgia. It usually resolves spontaneously. Pulmonary disease: 90% have abnormal CXRs with bilateral hilar
lymphadenopathy +/- pulmonary infiltrates/fibrosis. Symptoms: dry cough, progressive dyspnoea, ↓exercise tolerance & chest
pain. In 10-20%, symptoms progress with concurrent deterioration in lung function. Non-pulmonary signs: are legion:
lymphadenopathy; hepatomegaly; splenomegaly; uveitis; conjunctivitis; keratoconjuctivitis sicca; glaucoma; terminal
pharyngeal bone cysts; enlargement of lacrimal & parotid glands; bell’s palsy; neuropathy; meningitis; brainstem & spinal
syndromes; space-occupying lesion; erythema nodosum; lupus pernio; subcutaneous nodules; cardiomyopathy; arrhythmias;
hypocalcaemia; hypercalcuria; renal stones; pituratory dysfunction. Tests: Blood: ESR ↑, lymphopenia, LFT ↑, serum ACE ↑ in
~60%, Ca2+ ↑, ↑IG’s. 24h urine: Ca2+ ↑. Tuberculin skin test: -ve in 2/3; CXR abnormal in 90%: stage 0: normal stage 1: BHL
stage 2: BHL (bi hilar lymphadenopathy) + peripheral pulmonary infiltrates. Stage 3: peripheral pulmonary infiltrates alone
stage 4: progressive pulmonary fibrosis; bulla formation (honeycombing); pleural involvement. ECG may show arrhythmias or
bundle branch block. Lung function tests may be normal/showed reduced lung volumes, impaired gas transfer & restrictive
ventilator defect. Tissue biopsy is diagnostic & shows non-caseating granulomata. Kveim tests are now obsolete. Broncho-
alveolar lavage (BAL) shows ↑lymphocytes in active disease; ↑neutrophils with pulmonary fibrosis. US may show
nephrocalcinosis or hepatosplenomegaly. Bone X-RAYs show ‘punched out’ lesions in terminal phalanges. CT/MRI may be useful
in assessing severity of pulmonary disease or diagnosing neurosarcoidosis. Ophthalmology assessment is indicated in ocular
disease. Management: pts with BHL (bilateral hilar lymphadenopathy) don’t need treatment & most recovery spontaneously.
Acute sarcoidosis: bed rest & NSAIDs. Indications for corticosteroids: parenchymal lung disease, Uveitis, Hypercalcaemia,
Neuro/cardiac involvement. Prednisolone then ↓dose over 1yr according to clinical status. Other therapy: in severe illness: IV
methylprednisolone or immunosuppressant's (methotrexate, hydroxychloroquine, ciclosporin, cyclophosphamide) may be
needed. Anti- TNF- alpha therapy may be tried in refractory cases or lung transplantation. Prognosis: 60% of pts with thoracic
sarcoidosis resolve over 2yrs. 20% respond to steroids, the rest= improvement unlikely despite therapy.
 Amyloidosis

Mid pic shows amyloidosis + skin lesions.

 Amyloidosis

Bottom mid pic shows amyloid deposits in glomerulus disease

 amyloidosis

Group of disorders characterized by extracellular deposits of protein In abnormal fibrillar form, resistant to
degradation. The following are the systemic forms of amyloidosis. Amyloid deposition is also a feature of
Alzheimer's disease, type 2 DM & haemodialysis-related amyloidosis. AL amyloid (primary amyloidosis)
proliferation of plasma cell clone -> amyloido-genic monoclonal Igs -> fibrillar light chain protein deposition->
organ failure-> death. Associations: myeloma (15%) ; Waldenstrom’s, lymphoma. Organs involved: Kidney’s:
glomerular lesions- proteinuria & nephrotic syndrome. Heart: restrictive cardiomyopathy (looks ‘sparking’ in
echo), arrhythmias, angina. Nerves: peripheral & autonomic neuropathy; carpal tunnel syndrome. Gut:
macroglossia (big tongue), malabsorption/weight ↓, perforation, haemorrhage, obstruction & hepatomegaly.
Vascular: purpura, esp periorbital- a characteristic feature. Px: optimise nutrition, oral melphalan +
prednisolone extends median survival from 13m to 17m. High-dose IV melphalan with autologous peripheral
blood stem cell transplantation may be better. AA amyloid (secondary amyloidosis) here amyloid is derived
from serum amyloid A, an acute phase protein, reflecting chronic inflammation in rheumatoid arthritis,
UC/Crohn’s, familial Mediterranean fever & chronic infections- TB, bronchiectasis, osteomyelitis. It affects
kidneys, liver & spleen & may present with proteinuria, nephrotic syndrome or hepatosplenomegaly.
Macroglossia is not seen; cardiac involvement is rare. Px: manage underlying condition optimally. Familial
amyloidosis (autosomal dominant). Usually causes a sensory or autonomic neuropathy +/- renal/cardiac
involvement. Liver transplant can cure. Diagnosis: made with biopsy of affected tissue & +ve Congo Red
staining with red-green birefringence under polarised light microscopy. The rectum or subcutaneous fat are
relatively non-invasive for biopsy and are +ve in 80%. Prognosis: median survival is 1-2yrs. Pts with myeloma &
amyloidosis have a short survival than those with myeloma alone.
 vi tilig o

Typically white patches +/- hyper-pigmented borders. Sunlight makes them itch.
Associations: autoimmune disorders, premature ovarian failure. Treat by
camouflage cosmetics & sunscreens (+/- steroid creams +/- dermabrasion.
anaemia
 Anaemia

Anaemia is defined as low Hb conc. & may be due to either a low red cell mass or increased plasma volume e.g. in pregnancy. A
low Hb is <135g/L for men and <115g/L for women. Anaemia me be due to reduced production or increased loss of RBCs & has
many causes. These will often be distinguishable by history, exam, & inspection of blood film. Symptoms: due to underlining
cause/anaemia: fatigue, dyspnoea, faintness, palpations, headache, tinnitus, anorexia- and angina if there is pre-existing
coronary heart disease. Signs: may be absent even in severe anaemia. May be pallor (e.g. conjunctivae although not reliable). In
severe anaemia, there may be signs of hyper-dynamic circulation e.g. tachycardia, flow murmurs (ejection-systolic loudest over
apex) & cardiac enlargement/retinal haemorrhages. Later, HF may occur: rapid blood transfusions may be fatal. Types of
anaemia: first step in diagnosis is to look at mean cell volume (MCV) Low MCV- microcytic anaemia: 1) Iron-deficiency anaemia
(Most common cause) 2) Thalassemia (suspect if MCV too low for Hb level & red cell count is ↑). Definitive diagnosis needs
DNA analysis although finding a normal HbA2 with normal ferritin in a very microcytic pic is suggestive of possible alpha
thalassemia trait. 3) Sideroblastic anaemia (rare). NB: last 2 are conditions where there is an accumulation of iron, & so tests
will show serum iron ↑, ferritin ↑, & a low total iron-binding capacity (TIBC). Normal MCV (normocytic anaemia): 1) acute
blood loss 2) Anaemia of chronic disease (or ↓MCV) 3) bone marrow failure 4) renal failure 5) Hypothyroidism (↑MCV) 6)
Haemolysis (or ↑MCV) 7) pregnancy. If WCC ↓ or platelets ↓, suspect marrow failure. High MCV (macrocytic anaemia): 1) B12
or folate deficit 2) Alcohol excess/liver disease 3) Reticulocytosis 4) Cytotoxics e.g. e.g. hydroxycarbamide 5) Myelodysplastic
syndromes 6) Marrow infiltration 7) Hypothyroidism 8) Anti-folate drugs (e.g. phenytoin). Haemolytic anaemia's do not fit into
above classification as anaemia may be normocytic or if there are many young (larger) RBCs & reticulocytes, macrocytic.
Suspect if there is a reticulocytosis, mild macrocytosis, haptoglobulin ↓, bilirubin ↑ and urobilinogen ↑. Often mild jaundice
(but no bilirubin in urine as haemolysis causes pre-hepatic jaundice). Transfuse? – usually no! – unless severe acute anaemia. If
there is an acute cause (haemorrhage which active peptic ulcer e.g.) then transfuse. Chronic anaemia is better tolerated as is
important to ascertain cause e.g. iron-deficiency anaemia, iron supplements will raise haemoglobin in a safer & less costly way.
In severe anaemia with HF, transfusion is vital to restore Hb to a safe level but must be done with great care. Give packed cells
slowly with IV furosemide with alternate units- check for rising JVP & basal crackles. If CCF gets worse, stop & treat. If
immediate transfusion essential, a 2-3 unit exchange transfusion can be tried, removing blood at same rate as its transfused.
 Iron-deficiency anaemia (IDA)

Common (seen in ~14% of menstruating women). Causes: blood loss e.g. menorrhagia or GI
bleeding. Poor diet may cause IDA in babies/children (rarely in adults), those on special diets or
wherever there is poverty. Malabsorption e.g. coeliac disease causes refractory IDA. In the tropics,
hookworm (GI blood loss) is most common cause.
Signs: chronic IDA: Koilonychia (spoon-shaped nails), atrophic glossitis angular cheilosis (ulceration at
side of mouth) & rarely, post-cricoid webs.
Tests: Microcytic hypochromic anaemia with anisocytosis & poikilocytosis (pictures needed). ↓MCV,
↓MCH and ↓MCHC. Confirmed by ↓ferritin. ↑Red cell protoporphyrin. NB: ferritin is an acute
phase protein and ↑with inflammation e.g. infection, malignancy. Serum transferrin receptors are
also ↑in IDA but are less affected by inflammation. If MCV ↓, & good history of menorrhagia, oral
iron may be started without further tests. Otherwise investigate for GI blood loss: gastroscopy,
sigmoidoscopy, barium enema or colonoscopy, stool microscopy for ova if hookworm.
Treatment: oral iron e.g. ferrous sulphate, SE: nausea, abdominal discomfort, diarrhoea or
constipation, black stools. Hb should rise with modest reticulocytosis (young RBC)- continue until Hb
normal for at-least 3m to replenish stores. Usual reason that IDA fails to respond to iron replacement
is that the pt has rejected the pills- is the reason GI disturbance? Altering dose of elemental iron with
different prep may help. May be continued blood loss, malabsorption, anaemia of chronic disease or
misdiagnosis e.g. when thalassemia is to blame.
 Anaemia of ch ro nic disease (secondary anaemia)

Most common anaemia in hospital pts 2nd after IDA. 1) poor use of iron in
erythropoiesis 2) Cytokine-induced shortening of RBC survival 3)
↓production of & response to erythropoietin.
Causes: many e.g. chronic infection, vasculitis, rheumatoid, malignancy, renal
failure.
Tests: mild normocytic anaemia, ferritin normal or ↑. Do blood film B12,
folate, TSH & tests for haemolysis as anaemia is often multifactorial.
Treatment: treating underlining disease more vigorously may help. EPO is
effective in raising haemoglobin levels & ↑quality of life in pts with malignant
disease, SE: flu-like symptoms, HTN, mild rise in platelet count &
thromboembolism. Iron given parenterally can safely overcome functional
iron deficiency. Inhibitors of hepcidin & inflammatory modulators show
promise.
 Sideroblastic anaemia

Sideroblastic anemia comes about because of mutations in genes called ALAS2 and HFE. These mutations are what causes the red blood cells to not make
enough hemoglobin for good health. Because of this, the body makes up for the lack of iron by increasing its uptake of iron from the victim’s diet. The iron accumulates in
the internal organs and even in the skin. This disorder is called hemochromatosis. Because humans can’t excrete iron fast enough, the iron damages the organs of the body,
and may lead to failures of the heart, liver or kidneys. Transferrin, like ferritin, also balances the level of iron in the blood. With sideroblastic anemia, transferrin levels are
normal or low, but ferritin levels are high. Top right shows Refractory anemia with ringed sideroblasts- top mid pic also shows ringed sideroblasts along with bottom 2 pics.
 Sideroblastic anaemia

Microcytic anaemia does not equal iron deficiency! 20% of older ppl with a low
MCV are not iron deficient. -> think of sideroblastic anaemia whenever microcytic
anaemia not responding to iron. Do a ferritin look at a film (hypochromia) & a
marrow to look for disease defining sideroblasts.
Px: Remove cause. Pyridoxine may help +/- repeated transfusions for severe
anaemia.
 Pituitary CA

(a) Tumor revealing monomorphic population of round-to-spindly cells. (b) Invasive adenoma showing monomorphic tumor withan entrapped bony trabecula. (c) Pituitary carcinoma showing compact tumor cells.

Comparison of expression of MIB-1 in (a) pituitary adenoma, (b) recurrent invasive adenoma and (c) pituitary carcinoma
Pituitary CA
 Pituitary carcinoma

Account for 10% of intracranial tumours. Microadenoma <1cm and macroadenoma is >1cm. 3
histological types: 1) Chromophobe- 70%. Many are non-secretory, some cause hypopituitarism, half
produce prolactin (PRL); few produce ACTH or GH- local pressures affected in 30%. 2) Acidophil- 15%-
secret GH or PRL-local pressures affected in 10%. 3) Basophil- 15%- secret ACTH- local pressures
affected rarely. Symptoms are caused by pressure, hormones (e.g. galactorrhoea), or
hypopituitarism. FSH-secreting tumours can cause macro-orchidsm in men but rare. Features of local
pressure: headache, VF defects (bilateral temporal hemianopia due to compression of optic chiasm)
palsy of cranial nerves 3, 4, 5. also diabetes insipidus (DI); disturbance of hypothalamic centres of T,
sleep & appetite; erosion through floor of sella leading to CSF rhinorrhoea. Tests: MRI defines intra-
and supra-sellar extension; VF; screening tests: PRL, IGF-1, ACTH, cortisol, TFTs, LH/FSH, testosterone
in male, short Synacthen test. GTT if acromegaly suspected. Water deprivation tests if DI suspected.
Treatment: hormone replacement if needed. Ensure steroids given before levothyroxine as
thyroxine may precipitate adrenal crisis. Surgery: trans-sphenoidal surgery but if supra-sellar
extension, a trans-frontal approach may be used. For prolactinoma, 1 st line treatment is with
dopamine agonist. Pre-op: ensure IM hydrocortisone. Post-op: retest pituratory function to assess
replacement needs. Repeating dynamic tests for adrenal function >6w post-op. Radio: e.g.
sterostatic. Good for residual/recurrent adenomas (good rates of tumour control & normalisation of
excess hormone secretion). Post-op: recurrence may occur late after surgery so life-long follow up
needed. Fertility should be discussed: may reduce post-op due to ↓gonadotrophs.
 Pituitary carcinoma continued…

Pituratory apoplexy: Rapid pituratory enlargement from bleed into tumour may
cause mass effects, Cardiovascular collapse due to acute hypopituitarism & death.
Suspect if acute onset of headache, meningism, ↓GCS, opthalmoplegia/VF defect,
esp if known tumour (may present like subarachnoid haemorrhage). Px: urgent
steroids (IV hydrocortisone) & meticulous fluid balance +/- cabergoline
(dopamine agonist if PRL) +/- surgery.
Craniopharyngioma: not strictly a pituratory tumour: it originates from Rathke’s
pouch so is situated between pituratory & 3rd ventricle floor. Rare but commonest
childhood intracranial tumour. Over 50% present in childhood with growth failure;
adults may present with amenorrhoea, ↓libido, hypothalamic symptoms (e.g. DI,
hyperphagia, sleep disturbance) or tumour mass effect. Tests: CT/MRI (calcification
in 50% may also be seen on skull X-RAY). Treatment: surgery +/- post-op radio; test
pituratory function post-op.
 Epilepsy

A recurrent tendency to spontaneous intermittent, abnormal electrical activity in part of the brain, manifesting as
seizures. Convulsions are motor signs of electrical discharges. Many of us would have seizures in abnormal
metabolic circumstances- e.g. Na+ ↓, hypoxia (e.g. reflux anoxic seizures in faints). Prevalence of active epilepsy:
1%. Elements of a seizure: a prodrome lasting hrs or days may rarely precede the seizure- not part of seizure itself:
pts or others notice change in behaviour/mood. An aura is part of the seizure which the pt is aware & may precede
its other manifestations. The aura may be a strange feeling in gut or flashing lights. It implies a partial (focal) seizure,
often, but not necessarily, from temporal lobe. Post-ictally there may be headache, confusion, myalgia, sore tongue
or temp weakness after a focal seizure in motor cortex (Todd’s palsy) or dysphasia following a focal seizure in
temporal lobe. Causes: 2/3 are idiopathic. Structural: cortical scarring (e.g. head injury yrs before onset),
developmental (e.g. dysembroplastic neuroepithelial tumour/cortical dysgenesis), space-occupying lesion, stroke,
hippocampal sclerosis (e.g. after a febrile convulsion), vascular malformations. Others: Tuberous sclerosis,
sarcoidosis, LSE, PAN. Non-epileptic causes: trauma, stroke, haemorrhage, ↑ICP; alcohol or benzodiazepine
withdrawal; metabolic disturbance; liver disease; infection (e.g. meningitis, encephalitis, syphilis, cysticercosis, HIV);
T ↑; drugs (tricyclic's, cocaine, tramadol, theophylline); pseudo-seizures. Diagnosis: 1) are these really seizures?
Description from witness is vital- but asked if its reliable? Tongue-biting & slow recovery are very suggestive. Not
everything that twitches is epilepsy- reflex anoxic convulsions due to syncope are particularly difficult. Try hard not
to diagnose in error as it has consequences for employment, insurance and driving. 2) type of seizure? Partial or
general? Attacks onset is key- if it begins with focal features then its partial. 3) triggers? –alcohol, stress, fevers,
certain sounds, flickering lights/TV-induced fits rarely needs drugs.
 Epilepsy continued…

In assessing a first-ever seizure: is it really a first? Ask family and pt about past funny turns/odd behaviour. Deja-vu
& odd episodic feelings of fear may be relevant. Was seizure provoked? Provoked 1st seizures are less likely to recur
(3-10%- unless cause is irreversible e.g. infarct or glioma); if it was unprovoked, recurrence rates are 30-50%. NB:
provocations are different to triggers: most people would have a seizure given sufficient provocation but most
people do not have seizures however many triggers they are exposed to so triggered seizures suggest epilepsy-
triggered attacks tend to recur. Prompt investigation e.g. with admission for 24h bloods, drugs screen, LP (if safe),
EEG, CT/MRI enhancement. Admit to substantiate ideas of pseudo-seizures, or for recurrent seizures. Counselling:
after any ‘fit’, advise about dangers (e.g. swimming, driving, heights) until diagnosis is known; then give
individualised counselling on employment, sport, insurance and conception. Avoid driving until seizure free for 1yr>
say you must contact DVLA. Document this. Management: talking to pts e.g. giving advice on relaxation training,
smelling a pleasant smell if auria is a certain bad smell may abort say emotion triggered seizure better than drugs.
Drugs not advised after one fit unless risk of recurrence is high. After 2nd fit, discuss opts with pt- drugs probably
indicated. If only 1fit every 2yrs- pt may take risk of no drugs rather than taking drugs daily. Drug choice depends on
seizure type, epilepsy syndrome, other medications & co-morbidities, plans for pregnancy & pt preference.
Generalised tonic clonic seizures: Sodium Valproate or Lamotrigine (often better tolerated & less tetragenic) are 1st
line. Others: levetiracetam, oxcarbazepine, clobazam. Absence seizures: Sodium valproate, lamotrigine or
ethosuximide. Tonic, atonic and myoclonic seizures: as for generalised tonic-clonic seizures, but avoiding
carbamazepine and oxcarbazepine, which may worsen seizures. Partial seizures +/- secondary generalisation:
Carbamazepine is 1st then sodium valproate, lamotrigine, oxcarbazepine or topiramate. Others: levetiracetam,
gabapentin, tiagabine phenytoin, clobazam. Slowly build up doses over 2-3m until seizures are controlled/SE’s
bad/max dose reached. To switch drugs- introduce new drug then withdrawn 1st drug once 2nd drug established.
Dual therapy is necessary in <10% of pts consider if all appropriate drugs have been tried singly at optimum dose.
 Epilepsy continued…

Management: in 1st unprovoked fits, unequivocal epileptiform activity EEGs if non-

convulsive status is the problem. Other tests: MRI (structural lesions). Drug levels (is
pt taking tablets?). Magneto-encephalography (MEG), PET, cognitive assessment, and
ictal SPECT may help localise the epileptogenic focus when evaluating for epilepsy
surgery. Non-epileptic attack disorder (pseudo-or psychogenic seizures). These are
not infrequent: suspect this if there are uncontrollable symptoms, no learning
disabilities, and CNS exam, CT, MRI and EEG normal- may co-exist with true epilepsy.
If drugs don’t work: if a single epileptogenic focus can be ID’d such as hippocampal
sclerosis or a small low-grade tumour, neurosurgical resection offers up-to 70%
chance of seizure freedom, depending on loc of focus, with risk of causing focal
neuro defects such as memory impairment, dysphasia or hemianopia. An alternative
is vagal nerve stimulation which can reduce seizure frequency & severity in ~33%.
When it all goes wrong: sudden unexpected death in epilepsy (SUDIP) is more
common in uncontrolled epilepsy & may be related to nocturnal seizure-associated
apnoea/asystole. Those with epilepsy have a mortality rate 3-fold that of controls.
>700 epilepsy-related deaths are recorded/yr in UK; up-to 17% are SUDIPs.
 Seizure classification

Partial seizures focal onset, with features referable to a part of one hemisphere- often seen with underlining
structural disease. Simple partial seizure: awareness unimpaired, with focal motor, sensory (olfactory, visual etc.),
autonomic/psychic symptoms. No post-ictal symptoms. Complex partial seizures: awareness is impaired. May have
simple partial onset (=aura) or impaired awareness at onset. Most commonly arise from temporal lobe. Post-ictal
confusion is common with seizures arising from temporal lobe, whereas recovery is rapid after seizures in frontal
lobe. Partial seizure with secondary generalisation: in 2/3 of pts with partial seizures, electrical disturbance which
starts focally spreads widely causing a secondary generalised seizure which is typically convulsive. Primary
generalised seizures: simultaneous onset of electrical discharge throughout cortex, with no localising features
referable to only one hemisphere. Absence seizures: brief (<10s) pauses e.g. suddenly stops talking in mid-sentence
then carries on where left off- presents in childhood. Tonic-clonic seizures: loss of consciousness. Limbs stiffness
(tonic) then jerk (clonic)- may have one without the other. Post-ictal confusion & drowsiness. Myoclonic seizures:
sudden jerk of limb, face or trunk. Pt may be thrown suddenly to ground or have a violently disobedient limb. Atonic
(a-kinetic) seizures: sudden loss of muscle tone causing a fall. Infantile spasms: commonly associated with a
tuberous sclerosis.
 Seizure drugs SE’s

Carbamazepine: (as-slow release): leucopenia, diplopia, blurred vision, impaired

balance, drowsiness, mild generalised erythematous rash, SIADH.
Lamotrigine: maculopapular rash- occurs in 10% typically in 1st 8wks, esp if on
valproate; warn pts to see doctor at once if rash/flu symptoms develop; also
associated with hypersensitivity (fever, ↑LFTs, & disseminated intravascular
coagulopathy). Others: diplopia, blurred-vision, photosensitivity, tremor, agitation,
vomiting, aplastic anaemia.
Levetiracetam: psychiatric SEs common e.g. depression, agitation. Others: D&V,
dyspepsia, drowsiness, diplopia, blood dyscrasias.
Phenytoin: toxic, ↓intellect, depression, coarce facial features, acne, gum
hypertrophy, polyneuropathy, blood dyscrasias.
Sodium valproate: nausea very common.
Vigabatrin: only used in infantile spasms (due to high incidence of VF defects).
 Seizures- emergency (status epilepticus)

Status usually occurs in pts with known epilepsy. If its 1st presentation, chance of structural brain lesion
is high (>50%). Diagnosis of tonic-clonic status usually clear. Non-convulsive status (e.g. absence status
or continuous partial seizures with preservation of consciousness) may be more difficult: look for
subtle eye or lid movement. EEG may be helpful. Could pt be pregnant? (any pelvic mass)- if so,
eclampsia is likely diagnosis- check urine and BP- immediate delivery may be needed.
Management: 1) Open & maintain airway, lay in recovery position. Remove false teeth if poorly fitting,
insert oral/nasal airway, intubate if necessary. 2) O2 100% + suction (as required) 3) IV access and take
blood: U&E, LFT, FBC, glucose, Ca2+, toxicology screen if indicated, anticonvulsant levels 4) Slow IV
Bolus phase- to stop seizures: lorazepam (buccal midazolam is easier to use oral alternative if 10yrs>)
(beware of resp arrest during last part of injection- rectal if IV impossible), give 2nd dose if no response
within 10m 5) IV Thiamine if alcoholism/malnourishment suspected. IV glucose unless glucose known
to be normal. Treat acidosis if severe (contact ICU). 6) correct hypotension 7) IV infusion phase: if
seizures continue, start IVI phenytoin (beware ↓BP & CI if bradycardic or heart block), monitor ECG
and BP, alternative: diazepam infusion -> continuing seizures require expert help with paralysis &
ventilation with continuous EEG monitoring in ICU- most unusual for seizures to continue past this
phase- could be pseudo-seizure? Particularly, if there are odd features (pelvic thrusts, resisting
attempts to open lids & your attempts to do passive movements; arms & legs flailing around). 8) IV
dexamethasone if vasculitis/cerebral oedema (tumour) possible 9) General anaesthesia. Never spend
longer than 20m on someone with status epilepticus without having help from an anaesthetist.
Guillain barre syndrome
 Guillain-Barre syndrome

An acute inflammatory demyelinating polyneuropathy. Signs: a few weeks after an

infection, a symmetrical ascending muscle weakness starts. Triggers:
Campylobacter jejuni, CMV, mycoplasma, zoster, HIV, EBV, vaccinations. Triggers
cause antibodies which attack nerves. In 40%, no cause found. May advance
quickly affecting all limbs at once causing paralysis. Progressive phase of up to 4w
followed by recovery. Unlike other neuropathies, proximal muscles more affected
e.g. trunk, resp and cranial nerves esp (VII). Pain is common (e.g. back, limb) but
sensory signs may be absent. Autonomic dysfunction: sweating, ↑pulse, BP
changes, arrhythmias. Nerve conduction studies: slow conduction. CSF: ↑protein,
normal CSF WCC. Resp involvement (big danger) requires transfer to ITU. Do FVC
4hourly. -> ventilate sooner rather than later. Px: IV Ig’s. plasma exchange is good
too. Steroids may have a role. Prognosis: good. ~85% make a complete/near-
complete recovery. 10% unable to walk alone at 1yr. Complete paralysis compatible
with complete recovery. Mortality: 10%.
Dementia
 Dementia

Initial presentation is memory loss over months/yrs (if over days think stroke/infection, if weeks then depression).
Prevalence: rare if <55yrs; 5-10% if >65yrs; 20% if >80yrs; 70% if >100yrs. Diagnosis: good history from pt and
someone who knows them well. May be agitation, aggression, wandering, hallucinations, slow repetitious speech,
apathy, mood disturbance- depression common in dementia but can also cause cognitive impairment. Cognitive
testing: use a validated dementia screen such as AMTS, TYM or similar. Mental state exam may reveal anxiety,
depression or hallucinations. Physical exam may ID a physical cause of cognitive impairment, risk factors (esp for
vascular dementia) or parkinsonism. Investigations: FBC, ESR, U&E, Ca2+, LFT, TSH, autoantibodies, b12/folate;
syphilis serology. CT/MRI. Also EEG, CSF, functional imaging. Metabolic, genetic & HIV tests if indicated. Commonest
causes: Alzheimer’s disease. Vascular dementia ~25% of all dementias. It represents the cumulative effects of many
small strokes, thus sudden onset & stepwise deterioration is characteristics. Look for evidence of vascular pathology
(BP ↑, past strokes, focal CNS signs). Lewy body dementia: 3rd commonest cause (15-25%) after Alzheimers and
vascular causes, typically with fluctuating cognitive impairment, detailed visual hallucinations (e.g. small
animals/children) & later, parkinsonism. Histology is characterized by Lewy bodies in brainstem and neocortex.
Fronto-temporal (Pick’s dementia): frontal & temporal atrophy without Alzheimers histology; genes on
chromosome 9 are important as in MND. Signs: executive impairment; behaviour/personality change; early
preservation of episodic memory and spatial orientation; disinhibition; hyperorality, stereotyped behaviour and
emotional unconcern. Other causes: alcohol/drug abuse; repeated head trauma; pellagra, Whipple’s disease;
Huntington’s; CJD; Parkinson’s; HIV; cryptococcosis; familial autosomal dominant Alzheimer’s ; CADASIL.
 Dementia con tinued…

Management: care co-ordinator & social services to help with living at home.
Develop routines e.g. keeping the house keys in a specific place- habits that stay
even till late disease.
Drugs: first rule out infection/pain as cause of worsening behaviour. trazodone or
lorazepam PO. If agitation severe, get help: antipsychotics such as quetiaoine,
riseridone and olanzapine may improve positive symptoms, but cognition, verbal
fluency, and longevity may be worsened. Haloperidol can be useful in short term.
-> Avoid using antipsychotics for agitation in Lewy body dementia (↑ ↑risk of SE).
Some evidence that anticholinesterase inhibitors may help. Depression is
common. Try and SSRI e.g. citalopram or, if severe, mirtazapine. CBT can help with
social withdrawal & catastrophic thinking. Avoid drugs that impair cognition (e.g.
neuroleptics, sedatives, tricyclics)
MRSA
Typically a HSA causing pneumonia, septicaemia, wound infections & death
(risk ↑5-fold). It accounts for ~6% of total HSA. There are >17 sub-types.
Mandatory to record infection in UK. UK prevalence has fallen by 30% since
2010 despite ward overcrowding & reluctance to close affected ward,
perhaps due to better barrier-nursing facilities & improved hygiene
(washing hands between patients). Carriage rates (nasal) 1-10%. Risk
factors: HIV, dialysis, on ITU. MRSA is a community acquired in up-to 40%.
Px: Vancomycin or teicoplanin are used but strains with reduced sensitivity
have emerged. Here, consider linezolid or daptomycin. Prevention: isolate
recently admitted pts with suspected MRSA. Wash hands and stethoscope.
Ask about need for eradication. Be meticulous in looking after intravascular
catheters. Surveillance swabs of pts & staff in outbreak +/- whole genome
sequencing. Use gowns/gloves when dealing with infected/colonized pts.
Masks may be needed during contact with MRSA pneumonia.
 GI bleeding

Bottom left pic shows upper GI bleed. And top pic shows bleeding varices. Right pic shows GI bleed due to duodenal ulcer. Mid black pics show
melena which indicate GI bleed.
 GI bleeding

Hematemesis is vomiting of blood. Maybe bright red or look like coffee grounds. Melena means black motions often
like tar- and has characteristic smell of altered blood- both indicate upper GI bleed. Ask about: Past GI bleeds;
dyspepsia/known ulcers; known liver disease or oesophageal varices; dysphagia; vomiting; weight loss. Check drugs
& alcohol. Is there serious comorbidity (bad prognosis) e.g. CVD, resp disease, hepatic/renal impairment or
malignancy. Look for signs of chronic liver disease and do PR to check for melena. Is pt shocked -> do you feel faint
when you sit up? Also: peripherally shut down/cool & clammy; capillary refilling (CR) time >2s- urine output -
<1/2mL/Kg/h. Tachycardia, systolic BP. Do Rockall risking scoring:
Pre-endoscope O pts 1pt 2pts 3pts
Age <60 60-79 >80
Shock: systolic BP >100 pulse <100 BP >100 BO <100
BP & pulse rate Pulse >100
Co-morbidity Nil Major HF, Renal failure, Liver Metastases
ischaemic failure
heart
disease
Post-endoscope, Mallory-Weiss tear; All other Upper GI
diagnosis no lesion; no sign of diagnoses malignancy
recent bleed
Signs of recent None/ dark red spot Blood in upper GI
haemorrhage on tract; adherent
endoscope clot; visible vessel.
 GI bleeding continued…

Acute management: protect airway & give High-flow O2. then: Insert 2-large bore
IV cannula & take blood for FBC (early Hb may be normal because haemodilution
has not taken place yet), U&E, (↑urea out of proportion to creatinine is indicative
of a massive blood meal), LFT, clotting, and cross-match 4-6units. Give IV fluids to
restore intravascular volume while waiting for blood to be cross-matched. In dire
emergency- give group O Rh-ve Blood. Insert a urinary catheter & monitor hourly
urine output. Organise CXR, ECG and ABG. Consider a CVP line to monitor & guide
fluid replacement. Correct clotting abnormalities (Vit K), FFP, platelets). Monitor
pulse, BP and CVP at-least hourly until stable. IV bolus Omeprazole then
continuous IVI. Arrange an urgent endoscopy. Surgery. Further management:
anatomy is important in assessing risk of re-bleed: posterior DU’s are highest risk as
they are nearest to gastro-duodenal artery. Re-exam after 4h & ask about need for
FFP >4 units transfused. Hourly pulse, BP, CVP, urine output. Transfuse to keep
Hb>100g/L. check FBC, U&E, LFT and clotting daily. Keep nil by mouth for 24h.
Allow clear fluids after 24h & light diet after 48h as long as there is no evidence of
re-bleed.
Subarachnoid haemorrhage (SAH)
Often catastrophic. Incidence: 9/100k; typical age; 35-65. causes: rupture of saccular aneurysms (80%); arterio-venous
malformations. No cause is found in <15%. Risk factors: smoking, alcohol misuse, BP ↑, bleeding disorders, mycotic aneurysm
(female:male 3:2 if 45yo>). Close relatives have 3-5fold ↑risk of SAH. Berry aneurysms: common sites: junction of posterior
communicating with internal carotid or of anterior communicating with ACR or bifurcation of MCA. 15% are multiple. Some are
hereditary. Associations: polycystic kidneys, coarctation of aorta, Ehlers- Danlos syndrome (hypermobile joints with ↑skin
elasticity). Symptoms: sudden (usually but not always within sec’s) devastating typically occipital headache. Vomiting, collapse,
seizures and coma often follow. Coma/drowsiness may last for days. Signs: neck stiffness, Kerning’s sign (takes 6h to develop),
retinal, subhyaloid & vitreous bleeds (=Tersons syndrome; carries a worse prognosis: mortality ↑X5). Focal neurology at
presentation may suggest site of aneurysm (e.g. pupil changes indicating a 3 rd nerve palsy with a posterior communicating
artery aneurysm) or intra-cerebral haematoma. Later deficits suggest complications. Differentials: in primary care ~25% with
‘thunderclap’ headache have SAH. In 50-60% no cause found. Remainder have meningitis, migraine, intra-cerebral bleeds, or
cortical vein thrombosis. Sentinel headache: SAH pts may earlier have experienced a sentinel headache- perhaps due to small
warning leak from offending aneurysm~6%, but re-call bias clouds picture. As surgery is more successful in least symptomatic,
be suspicious of any sudden headache esp with neck/back-pain. Tests: CT detects >90% of SAH within the 1st 48h. LP if CT –ve
and no CI >12h after headache onset. CSF in SAH is uniformly blood early on & becomes xanthochromic (yellow) after several
hours due to breakdown products of Hb (bilirubin). Finding xanthochromic confirms SAH, showing that LP was not a ‘bloody
tap’. Management: refer all proven SAH to neurosurgery immediately. Re-exam CNS often; chart BP; pupils and GCS- repeat CT
deteriorating. Maintain cerebral perfusion by keeping well hydrated & aim for SBP>160, treat ↑BP only if very severe.
Nimodipine PO, a Ca2+ antagonist that reduces vasospasm & consequent morbidity from cerebral ischemia. Endovascular
coiling preferred. Do catheter or CT angiography to ID single vs multiple aneurysms before intervening. Intracranial stents &
balloon remodelling enable treating wide-necked aneurysms. Micro catheters can now traverse tortuous vessels to treat
previously unreachable lesions. Complications: Re-bleeding is commonest cause of death~occurs in 20% in 1 st few days.
Cerebral ischemia due to vasospasm may cause a perm CNS deficit & is commonest cause of morbidity. If this happens, surgery
not helpful at time but maybe later. Hydrocephalus due to blockage of arachnoid granulations, requires a ventricular/lumbar
drain. Hyponatraemia is common but should not be managed with fluid restriction.
 Rectal bleeding

Top mid pic shows ischaemic colitis and bottom left pic shows bowel perforation.
 Rectal bleeding

free gas under diaphragm (pneumoperitoneium) (air trapped in peritoneal cavity) on top right pic is suggestive of bowel perforation or due to insufflation of gas
during laparoscopy. All 3 pics show free gas.
 Rectal b leeding

Causes: Diverticulitis, colorectal cancer, haemorrhoids, Crohn’s; UC, perianal

disease, Angiodysplasia, Rarities- trauma, ischaemic colitis, radiation proctitis,
aorto-enteric fistula. ABC resus if necessary. History and exam. Blood tests: FBC.
U&E, LFT, clotting, amylase (pancreatitis), CRP, group & save- await Hb result before
cross matching unless stable & bleeding. Imaging may only need plain AXR, but
signs of perforation then do erect CXR. Fluid management: insert 2 cannulae into
anti-cubital fossa. Insert a urinary catheter if suspicion of haemodynamic comp.
give crystalloid as replacement and maintenance IVI. Blood transfusions rarely
needed in acute setting. Antibiotics may occasionally be needed if evidence of
sepsis or perforation e.g. IV cefuroxime + metronidazole. PPI: IV omeprazole ~15%
are from upper GI bleeds. Keep bedbound: pt may need to pass stool but could be
another large bleed, resulting in collapse if they try walk -> don’t allow them to
mobilize & inform nursing staff of this. Start a stool chart to monitor volume &
frequency of motions , send sample for MC&S. diet keep on clear fluids so that
they can have something, yet colon will be clear for colonoscopy. Surgery= main
indication for this is unremitting, massive bleeding.
 Acute mesenteric ischaemia

CT on top left showing ischaemic bowel due to thrombosis of superior mesenteric vein. Top mid shows mesenteric ischaemia due to atherosclerosis of
arteries. Mid shows same thing.
  
Acute mesenteric ischemia

Almost always involves small bowel & may follow superior mesenteric artery (SMA) thrombosis or
embolism, mesenteric vein thrombosis or non-occlusive disease. Arterial thrombosis becoming
commonest cause of acute ischemia as embolism becomes rarer. Venous thrombosis is more
common in younger pts with hypercoagulable states & tends to affect smaller lengths of bowel. Non-
occlusive ischemia occurs in low-flow states & usually reflects poor cardiac output, though there may
be other factors such as recent cardiac surgery/renal failure. Presentation: -> acute severe abdominal
pain; no abdominal signs; rapid hypovolaemia -> shock. Pain tends to be constant, central or around
RIF. Degree of illness often far out of proportion with clinical signs. Tests: may be ↑Hb (due to plasma
loss), WCC ↑, modestly raised plasma amylase, & a persistent metabolic acidosis. Early on,
abdominal X-RAY shows a ‘gasless’ abdomen. Arteriography helps but many diagnoses are only made
on finding a nasty necrotic bowel at laparotomy. CT/MRI angiography provides a non-invasive
alternative to simple arteriography. Measurement of mucosal O2 tension & MR oximetric
measurements of superior mesenteric vein flow are emerging as diagnostic tools. Treatment: main
life-threatening complications secondary to acute mesenteric ischemia are 1) septic peritonitis 2)
progression of SIRS into MODS, mediated by bacteria translocation across dying gut wall. Resus with
fluid, antibiotics (gentamicin + metronidazole) & usually heparin are required. If arteriography is
done, thrombolytics may be infused locally via catheter. At surgery dead bowel must be removed.
Revascularization may be attempted on potentially viable bowel but difficult and needs 2nd
laparotomy. Prognosis: poor for arterial thrombosis & non-occlusive disease (<40% survive), though
not so bad for venous & embolic ischemia.
 Chronic mesenteric ischaemia

Top left pic shows Chronic mesenteric ischemia is in the majority of cases associated with superior mesenteric artery stenosis (76% of
our cases). Bottom left shows partial superior mesenteric artery thrombosis.
 C hro nic m es e nte ric is c he mia

AKA intestinal angina. The triad of severe, colicky post-prandial abdominal pain
(‘gut claudication’), ↓weight (eating hurts), upper abdominal bruit may be present
+/- PR bleeding, malabsorption and N&V. there is often a history of vascular
disease. Rare and difficult to diagnose.
Tests: CT angiography & contrast enhanced MR angiography replacing traditional
angiography. Dopplar USS may be useful.
Treatment: once diagnosis is confirmed, surgery should be considered due to
ongoing risk of acute infarction. Percutaneous trans-luminal angioplasty & stent
insertion is replacing open revascularization. It is associated with less post-op
morbidity & mortality but higher restenosis rates.
 Chronic colonic ischemia

AKA ischaemic colitis usually follows low flow in inferior mesenteric artery (IMA)
territory & ranges from mild ischemia to gangrenous colitis. Presentation: lower
left-sided abdominal pain +/- bloody diarrhoea. Tests: CT may be helpful but
colonoscopy & biopsy is ‘gold-standard’. Barium enema shows characteristics
‘thumb printing’ of sub-mucosal swelling. Treatment: usually conservative with
fluid replacement & antibiotics. Most recover but strictures are common.
Gangrenous ischaemic colitis (presenting with peritonitis & hypovolemic shock)
requires prompt resus (followed by resection of affected bowel & stoma
formation). Mortality high.
MS
 MS

Cause: discrete plaques of demyelination occur at multiple CNS sites, from T-cell mediated immune response. Demyelination heals
poorly, causing relapsing and remitting symptoms. Prevalence: commoner in temperate areas (England 42:100k, Scotland 200:100k,
rarer in black Africa/Asia.) lifetime UK risk 1:1000. mean age of onset: 30 yrs, female:male 3:1. early exposure to sunlight/vit D is
important and vit D status relates to prevention of MS and a fewer symptoms and lesions on MRI in MS. Presentation: usually
monosymptomatic: unilateral optic neuritis (pain on eye movement and rapid ↓central vision); numbness or tingling in limbs; leg
weakness; brainstem or cerebellar symptoms (e.g. diplopia, ataxia). Other signs: sensory: dysaesthesia, pins & needles, vibration
sense ↓, trigeminal neuralgia. GI: swallowing disorders, constipation. Eye: Diplopia, hemianopia, optic neuritis, visual pneumena,
bilateral inter-nuclear opthalmoplegia, pupil defects. Motor: spastic weakness, Myelitis. Cerebellum: trunk & limb ataxia; intention
tremor; scanning (monotonous) speech; falls. Sexual/GU: ED, anorgasmia; urine retention; incontinence. Cognitive/visuospatial
decline: a big cause of unemployment, accidents/isolation. Amnesia; mood ↓or ↑; executive functioning ↓. Symptoms may worsen
with heat (e.g. hot bath) or exercise. Rarely polysymptomatic. Progression: early on, relapses (which can be stress induced) may be
followed by remission & full recovery. With time, remissions are incomplete, so disability accumulates. Steady progression of disability
from outset also occurs, while some pts exp no progressive disability at all. Poor prognostic factors: older male; motor signs at onset;
many relapses early on; many MRI lesions; axonal loss. Px: encourage a happy, stress-free life if possible (↓stress can reduce
development of new lesions). Minimise disability (disabled living foundation). If poor diet or ↓sun exposure, give Vit.D to achieve
serum 25(OH)D levels of >50nmol/L. Px: encourage a happy, stress-free life if possible (↓stress can reduce development of new
lesions). Minimise disability. If poor diet/ ↓sun exposure give Vit D to achieve serum 25(OH)D Levels >50nmol/L. steroids:
methylprednisolone PO shortens acute relapses, use sparingly- doesn’t alter overall prognosis. INF : ↓relapses by 30% & ↓lesion
accumulation on MRI, SE: flu symptoms, depression, abortion. Monoclonal antibodies: alemtuzumab acts against T cells in relapsing-
remitting MS- 2 trials show better than INF, SE: infections, while immune system reconstitutes itself; autoimmune disease (thyroid,
kidney, skin). Natalizumab acts against VLA-4 receptors that allow immune cells to cross blood-brain barrier. It ↓relapses by 68% &
↓MRI lesions by 92%, SE: progressive leucoencephalopathy; anti-body mediated resistance. Non-immunosuppressives: Glatiramer;
Mitoxantrone. Other drugs: Azathioprine may as good as INF for relapsing-remitting MS & is 20X cheaper. Palliation: Spasticity:
Baclofen PO, Diazepam (addictive), dantrolene, tizanidine. Endocannabinoid system modulation (sativex) has a role. Tremor:
Botulinum toxin type A injections improve tremor & functioning. Urgency/frequency: if post-micturition residual urine >100mL, teach
intermittent self-catheterization, if <100mL try tolterodine.
 Paracetamol overdosing

150mg/kg or 12g in adults can be fatal. However, promt treatment can prevent liver failure and death. 1tablet= 500mg.
• Signs and symptoms: none/vomiting initially +/- RUQ pain. Later: jaundice and encephalopathy from liver damage (main
danger) +/- renal failure. Investigations:
• Paracetamol levels
• U&E, creatine- to look for renal failure and have a baseline
• LFT may be normal if pt presents early but may rise to ALT >1000 IU/L this is the enzyme level taken to indicate
hepatotoxicity
• Glucose: hypoglycaemia is common in hepatic necrosis and capillary blood glucose should be checked hourly
• Clotting screen- prothrombin time is the best indicator of severity of liver failure and the INR should be checked 12-hourly
• ABG- acidosis can occur at a very early stage, even when pt is asymptomatic

Treatments:
 
• Give activated charcoal if overdose less than an hour
• If <8h since overdose start N-acetylcysteine if plasma paracetamol above treatment line, if >8h start N-acetylcyesteine
stopping only if level below treatment line
• N-acetylceystine is given IVI: with dextrose slowly. Rash is common SE- treat with chlorophenamine & stop, do not stop
unless anaphylatoid reaction with shock. An alternative is methionine PO.
Opioid overdose
 Opioid overdosing

Symptoms: Opiate poisoning may be a chronic problem, in which case the main complaint will be of
constipation. There may be nausea, vomiting or just loss of appetite. There may be sedation and
craving for the next dose.
Acute toxicity presents with drowsiness that will be more severe if there is also alcohol involved, or
involvement of other sedatives. There may be nausea or vomiting
Signs: Respiratory depression may be apparent. Hypotension and tachycardia are possible. There are
usually pinpoint pupils but this sign may be absent if other drugs are involved.
Differentials: Diabetic ketoacidosis, Hypercalcaemia, Hypernatraemia, Hyperosmolar
hyperglycaemic nonketotic coma, Hypoglycaemia, Hyponatraemia, Hypothermia, Meningitis, Stroke,
Subdural haematoma, Syncope.
Investigations: U&E, Paracetamol blood lvl, naloxone test- will produce severe withdrawl symptoms
if pt opiate dependant, FBC, ABG, creatine kinase, metabolic screen. CXR is pulmonary edema
suspected. Abdominal CXR if abdominal packages suspected. ECG for all.
Management: oxygenate and clear away and ventilate if needed. Give naloxone if coma/resp
depression present, larger doses may be required, repeat if needed. Observe pt for resp and CNS
depression. Give naloxone for heroin ASAP. Infused naloxone if repeats are needed. Oral activated
charcoal if airway protected. Naltrexone for pt who had been opioid dependant but and now opioid
free. If body packages of opioid suspected/confirmed- administer whole body irrigation.
 Benzodiazepine poisoning

Give IV Flumazenil (for resp arrest), slowly decrease dose. May provoke fits.
 C O poi s on ing

Hand pic shows cyanosis (hypoxia). Body shows typical red discoloration of fatal poisoning.
 Carbo n mon oxide p oison in g

Despite hypoxemia, skin is pink (or pale), not blue, as carboxyhaemoglobin (COHb)
displaces O2 from Hb binding sites. For same reasons, Sp02 from pulse oximeter
may be normal. Check ABG in co-oximeter (ie ensure it measures haemoglobin,
SaO2, Meth-Hb and COHb) which will show low SaO2 and High CoHb (normal <5%).
Symptoms: headache, vomiting, pulse ↑, tachypnoea, and if COHb>50%, fits,
coma and cardiac arrest.
Treatment: remove source. Give 100% O2 until COHb<10%. Metabolic acidosis
usually responds to correction of hypoxia. If severe, anticipate cerebral oedema &
give IVI mannitol. Confirm diagnosis with ABG quickly as levels may soon return to
normal. Monitor ECG.
Cyanide poisoning
 Cyanide poisoning

Fast killing poison has affinity for Fe3+ & inhibits cytochrome system, ↓aerobic
resp (hence pts are acidotic with raised lactate). Depending on degree of poisoning
presentation can be: mild: dizziness, anxiety, tachycardia, nausea,
drowsiness/confusion. Moderate: vomiting, reduced consciousness, convulsions,
cyanosis. Severe: deep coma, fixed unreactive pupils, cardioresp failure,
arrhythmias, pulmonary oedema.
Treatment: 100% O2, GI decontamination. If mild, supportive care is usually
sufficient. If moderate/severe then specific treatment to bind cyanide is required.
Give sodium nitrite/thiosulfate or IV dicobalt edetate then IV glucose or
hydroxycobalamin (cyanokit).
 Ecstasy poisoning

Ecstasy is a semi-synthetic, hallucinogenic substance (MDMA). It affects a range

from nausea, muscle pain, blurred vision, amnesia, fever, confusion and ataxia to
tachyarrhythmia's, hyperthermia, hyper/hypotension, water intoxication, DIC, K+,
acute kidney injury, hepatocellular and muscle necrosis, cardiovascular collapse
and ARDS. No antidote and treatment is supportive.
Management: administration of activated charcoal & monitoring of BP, ECG and
temp for at least 12h (rapid cooling may be needed). Monitor urine output & U&E,
LFT, CK, FBC, & coagulation. Metabolic acidosis may benefit from treatment with
bicarbonate. Anxiety: diazepam PO. Narrow complex tachycardia's in adults:
consider IV metoprolol. HTN can be treated with nifedipine PO or IV
phentolamine. Hyperthermia: attempt to cool, if rectal T >39, consider IV
dantrelone. Hyperthermia with MDMA is akin to serotonin syndrome and
propranolol, muscle relaxation and ventilation may be needed.
 Or gan oph os ph ate ins ect icid es

Inactivates cholinesterase- the resulting increase in acetylcholine causes SLUD response:

Salivation, lacrimation, urination and diarrhoea. Also look for sweating, small pupils, muscle
fasciculation, coma, resp distress and bradycardia.
Treatment: wear gloves; remove soiled clothes. Wash skin. Take blood (FBC & serum
cholinesterase activity). Give IV atropine till full atropinisation (skin dry, pulse >70, pupils
dilated). Up to 3d treatment may be needed. Also give IVI pralidoxime. Even if fits not
occurring, IV diazepam slowly seems to help.
Digoxin poisoning
Digoxin poisoning
Symptoms: Cognition ↓, yellow-green visual halos, arrhythmias,
nausea & anorexia. If serious arrhythmias are present, correct
hypokalaemia, & inactivate with digoxin-specific antibody fragments
(DigiFab). If load/level is unknown, give 20 vials. Consult
Compendium/SPC. If amount of digoxin ingested is unknown, the SPC
will tell you how much DigiFab to give.
Iron poisoning
Give IV Desferrioxamine. NB: gastric lavage if iron ingestion in last hr;
consider whole bowel irrigation.
Oral anticoagulants poisoning
If major bleed, treat with IV vitamin K, slowly. Give IV prothrombin
complex concentrate (or if unavailable, IVI fresh frozen plasma). For
abnormal INR with no (or minimal) bleeding. If it is vital anticoagulation
continues, enlist expert help. Discuss with haematology. NB:
coagulation defects may be delayed for 2-3d following digestion.
Phenothiazine (e.g. chloropromazine)
poisoning
Dystonia (torticollis, retrocollis, glossopharyngeal dystonia,
opisthotonus): try procyclidine e.g. IM/IV. Treat shock by raising legs
( +/- IVI plasma expander or inotropes if desperate). Restore body
temp. monitor ECG. Avoid lidocaine in dysrhythmias. Use IV lorazepam
for prolonged fits in usual way. Neuroleptic malignant syndromes
consist of: hyperthermia, rigidity, extrapyramidal signs, autonomic
dysfunction (labile BP, pulse ↑, sweating, urinary incontinence),
mutism, confusion, coma, WCC ↑, CK ↑; it may be treated with
cooling. IV Dantrolene can help, bromocriptine & amantadine are
alternatives.
Carbon tetrachloride poisoning
This solvent, used in many industrial processes, causes vomiting, ab
pain, diarrhoea, seizures, coma, renal failure, & tender hepatomegaly
with jaundice and liver failure. IV N-acetylcysteine may improve
prognosis.
 Paraquat poisoning

(found in weed killers). This causes D&V, painful oral ulcers, alveolitis,
and RF. Diagnose by urine test (sodium dithionite looked for). Give
activated charcoal at once followed by a laxative. Avoid O2 early on
(promotes lung damage).
Salicylate poisoning
 Salicylate poisoning (aspirin)

Aspirin is a weak acid with poor water solubility. It is present in many over the counter preps.
Uncoupling of oxidative phosphorylation leads to anaerobic metabolism & production of lactate
& heat. Effects are dose related & potentially fatal. 500mg/kg= severe 700mg/kg= fatal. Signs &
symptoms: vomiting, dehydration, hyperventilation, tinnitus, vertigo, sweating. Rarely ↓GCS,
seizures, ↓BP, heart block, pulmonary oedema, hyperthermia. Pts present initially with resp
alkalosis due to direct stimulation of central resp centres & then develop metabolic acidosis.
Hyper or hypoglycaemia may occur. Management: general: correct dehydration. Keep pt on ECG
monitor. Give activated charcoal to all present <1h- consider even if delayed presentation, slow
release formations or bezoar formation (can delay absorption): at least one dose. Consider
repeat doses. 1 Bloods: paracetamol and salicylate level, glucose, U&E, LFT, INR, ABG, HCO3,
FBC. Salicylate level may need to be repeated after 2h, due to continuing absorption if a
potentially toxic dose has been taken. Monitor blood glucose 1-2hrly, beware hypoglycaemia, if
severe poisoning, monitor salicylate levels, serum pH and U&E. 2 urine: check pH, consider
catheterisation to monitor output and pH. 3 correct acidosis: if plasma salicylate level >500mg/L
or severe metabolic acidosis, consider alkalinisation of urine with IV sodium bicarbonate. Aim for
urine pH 7.5-8 NB: monitor serum K+ as hypokalaemia may occur, and should be treated. 4.
dialysis may well be needed if salicylate >700mg/L, and if AKI or heart failure,
pulmonary/cerebral oedema, confusion or seizures, severe acidosis despite best medical therapy,
or persistently ↑plasma salicylate.
Anaphylactic shock
 Anaphylactic shock

Type-I IgE-mediated hypersensitivity reaction. Release of histamine & other agents

causes: capillary leak; wheeze; cyanosis; oedema (larynx, lids, tongue, lips); urticarial.
More common in atopic individuals. An anaphylactoid reaction results from direct
release of mediators from inflammatory cells, without involving antibodies, usually in
response to a drug e.g. acetylcysteine. Examples of precipitants: drugs e.g. penicillin,
contrast media in radiology. Latex. Stings, eggs, fish, peanuts, strawberries, semen (rare).
Signs & symptoms: itching, sweating, diarrhoea, vomiting, erythema, urticarial and
oedema. Wheeze, laryngeal obstruction, cyanosis. Tachycardia and hypotension. Mimics
of anaphylaxis: Carcinoid, phaeochromocytoma, systemic mastocytosis, hereditary
angioedema. Management: secure airway- give 100% 02, intubate if resp obstruction
imminent. Remove cause; raising feet may help restore circulation. Give IM adrenaline.
Repeat as guided by BP, pulse, resp function until better. IV chlorophenamine and
hydrocortisone. IV saline may be needed- titrate against BP. If wheeze, treat for asthma-
may require ventilator support. If still hypotensive, admission to ICU & IVI of adrenaline
may be needed +/- aminophylline & nebulized salbutamol. Further: measure mast cell
tryptase 1-6h after suspected anaphylaxis. Continue chlorophenamine PO if itching. Skin
prick tests showing specific IgE help ID allergens to avoid.
 Snakes (adders)

Anaphylaxis (see previous slide). Signs of envenoming: BP ↓(vasodilation), viper

cardio-toxicity; D&V; swelling spreading proximally within 4h of bite; bleeding gums
or venepuncture sites; anaphylaxis; ptosis; trismus; rhabdomyolysis; pulmonary
oedema. Tests: WCC ↑, urine RBC ↑; platelets ↓; PaO2 ↓; CK ↑, ECG.
Management: avoid active movement of affected limb (use splints/slings). Avoid
incisions & tourniquets. -> get help from local/national poisons service. Is
antivenom indicated IgG from venom-immunized sheep.
Giardiasis- Giardia lamblia
 Gia rdia s i s - G ia rdia la mbl ia

Giardia lamblia is a flagellate protozoon that lives in the dueodenum & jejunum.
Spread: faecal-oral (↑risk if e.g. immunosuppression, travel, anal sex, achlorhydria,
playgroups, swimming, pets or birds and drinking water contamination).
Pt: often asymptomatic. Lassitude, bloating, flatulence, ab pain, loose stools +/-
explosive diarrhoea are typical. Malabsoprtion, weight loss and lactose intolerance
may occur.
Investigations: stool microscopy for cysts & trophozoites may be –ve so repeat >3x.
Duodenal fluid aspirate analysis. Stool ELISA/PCR. Therapeutic trial. Any cause of
diarrhoea, sprue, celiac.
Px: Scrupulous hygiene. Tinidazole PO (avoid alcohol); if pregnant: paromomycin
PO. If this fails, check compliance and treat entire family. If diarrhoea persists,
avoid milk as lactose intolerance may perist for 6w.
 Testicular CA

US in top mid pic compare a normal testis (right) to a semioma (left). Right US shows seminoma. Left CT shows mets to chest suggesting stage 3 test CA.
 Testicular cancer

Commonest maliginacy in males aged 15-44. 10% occur in descended testicles

even after orchidopexy. A contralateral tumour is found in 5%. Types: seminoma
(55% of 30-65yrs), non-seminomatous germ cell tumour, 33%; mixed germ cell
tumour, 12%; lymphoma. Signs: typically painless testis lump, found after
trauma/infection +/- haemospermia, secondary hydrocele, pain, dyspnoea (lung
mets), ab mass (enlarged nodes), or effects of secreted hormones. 25% of
seminomas & 50% of NSGCTs present with mets. Risk factors: undescended testis,
infant hernia, infertility. Staging: 1) no evidence of mets 2) Infradiaphragmatic node
involvement (spread via para-aortic nodes) 3) supradiaphragmatic node
involvement 4) lung involvement (haematogenous). Tests: CXR, CT, excision biopsy.
Alpha-fp & B-HCG are useful tumour markers & help monitor treatment; check
before drain and Px. Px: radical orchidectomy. Seminomas exquisitely
radiosensitive. Stage 1: orchidectomy + radio cures ~95%. Do close follow-up to
detect relapse. Cure of NSGCT even if mets are present, achieved by 3 cycles of
bleomycin + etoposide + cisplastin. Prevention of late presentation: self-exam. 5yr
survival >90% all groups.
 Local An aesthetic to xicity

Starts with peri-oral tingling and paraesthesiae, progressing to drowsiness,

seizures, coma and cardioresp arrest. If suspected (pt feels funny and starts to
develop early signs), then stop administration at once and commence ABC
resus. Local anaesthetics are basic so don’t work well in acidic enviroments
such as abscesses. 1%= 10mg/mL.
 Multiple Myeloma (mm)

Top right pic shows amyloidosis infiltrating tongue in MM.

 mm

Top left pic shows bone tumours= male aged 55 presented with 7m Hx of back pain. Top right shows destructive lesions in right ribs with pathological fractures. Multiple punched
out lesions on skull. Top mid shows lytic lesions on left ribs with patho fractures. Left pic shows punched out lesions in clavarium (top front of head). Right pic shows compression
fractures of vertebral bodies with lesions. Bottom right pic shows lytic areas in clavaria. More here= http://www.mypacs.net/cases/MULTIPLE-MYELOMA-57083212.html
 Multiple myeloma: the chief plasma cell dyscrasia (PCD)

PCDs are due to an abnormal proliferation of a single clone of plasma or lymphoplasmacytic cells leading to
secretion of Igs or an Ig fragment causing dysfunction of many organs (esp kidney). The Ig is seen as a monoclonal
band or paraprotein, on serum or urine electrophoresis. Classification: based on Ig product – IgG in ~2/3, IgA in
~1/3. very few are IgM or IgD. Other Ig levels are low (‘immunoparesis’, causing ↑susceptibility to infection). In
~2/3, urine contains Bence-Jones proteins, which are free Ig light chains of kappa (K) or lambda (A) type, filtered by
kidney. Incidence: peak age: 70 yrs. Males:female : 1. Afro-Caribbeans:Caucasians= 2:1. symptoms: do serum
protein electrophoresis & ESR on all over 50 with back pain. Osteolytic bone lesions causing headache, pathological
fractures (e.g. long bones or ribs) vertebral collapse. Hypercalcaemia may be symptomatic. Lesions are due to
↑osteoclast activation, from signalling by myeloma cells. Anaemia, neutropenia or thrombocytopenia may result
from marrow infiltration by plasma cells, leading to symptoms of anaemia, infection and bleeding. Recurrent
bacterial infections due to immunoparesis, & also because of neutropenia due to disease and from chemo. Renal
impairment due to light chain deposition seen in up to 20% at diagnosis- mainly caused by precipitation of light
chains with Tamm-Horsfall protein in Distall loop of henle. Also, monoclonal Igs induce changes in glomeruli. A rare
type of damage is deposits of light chains in form of AL-amyloid & subsequent nephrosis. Tests: FBC- normocytic
normochromic anaemia, film- rouleaux formation, persistently ↑ESR or PV, ↑urea and creatinine, ↑Ca2+ (in ~40%),
alk phos usually normal unless healing fracture. Marrow. Screening test: serum and urine electrophoresis. B2-
macroglobulin. Imaging: X-rays: lytic ‘punched-out’ lesions e.g. copper-pot skull, vertebral collapse, fractures or
osteoporosis. CT/MRI may be useful to detect lesions not seen on XR. Diagnosis criteria: e.g. in bone pain or back
pain which is not improving, do ESR & film and electrophoresis. 1) monoclonal protein band in serum or urine
electrophoresis 2) plasma cells ↑on marrow biopsy 3) evidence of end-organ damage from myeloma:
hypercalcaemia, renal insufficiency, anaemia. 4) bone lesions: X-rays of chest, all of spine; skull; pelvis.
 Multiple myeloma continued…

Treatment: supportive: bone pain should be treated with analgesia (avoid NSAIDs due to risk of renal
impairment). Give all pts a bisphosphonate (a –ronate) as they reduce fracture rates and bone pain.
Local radio can help rapidly in focal disease. Orthopaedic procedures may be helpful in vertebral
collapse. Anaemia should be corrected with transfusion or EPO. Renal failure: rehydrate, and ensure
adequate fluid intake of 3L/day to prevent further renal impairment by light chains. Dialysis may be
needed in acute renal failure. Infections: treat rapidly with broad-spectrum antibiotics until culture
results known. Regular IV Ig infusions may be needed if recurrent. Chemo: If unsuitable for intensive,
Px: melphalan + prednisolone is used. This can control disease for ~1yr, reducing paraprotein levels
and bone lesions. Adding bortezomib increases time to relapse. In due course, disease may become
uncontrollable and resist treatment. Adding thalidomide improves event free survival e.g. in elderly.
SE: birth defects, drowsiness, neuropathy, neutropenia, sepsis, orthostatic hypotension;
thromboembolism (aspirin or full anticoagulation is probably wise if ↑risk e.g. hyperviscosity, or
other comorbidities). In fitter people, a more vigorous approach useful (high-dose therapy and stem
cell rescue, HDT) with VAD type regimen: Vincristine, Adriamycin and Dexamethasone. Autologous
stem cell transplant may then be done which improves survival but not curative. Allogenic transplant
can be curative in younger pts but carries ↑risk of mortality~30%. Thalidomide or bortzecomib may
be tried in relapsed disease. NB: lenalidomide is similar to thalidomide and being more potent may
have a role as may bendamustine (drives cell death by promoting mitotic catastrophe in melphalan-
resistant myeloma cells). Prognosis: worse if >2 osteolytic lesions, B2-macroglobulin >5.5, Hb <11g ,
albumin <30. cause of death: infection; RF.
 Idiopathic PD

Presentation: Bradykinesia/hypokinesia + 1 more of: tremor at rest (one side worse), postural instability +/- muscular rigidity.
Other signs may be subtle e.g. poor decoding of emotional content of speech (prosody), poor executive functioning and REM
sleep disorders. Poor simulatenous motor and cognitive functions can lead to freezing while walking (a devastating symptom).
Typical age of onset: 65yrs. Prevelence: 0.6% at 60-64; 3.5% at 85-89 (EU). Pathology: mitochondrial DNA dysfunction causes
degeneration of dopaminergic neurons in substantia nigra pars compacta (associated with Lewy bodies), hence ↓striatal
dopamine levels. Px: take your time, explain how you will assemble MDT to boost quality of life. Weight lifting has been
‘validated’ as superior to simple fitness programmes. Postural exercises e.g. Chinese qigoing help. Drugs: NICE recommends
referring to neurologist before drugs used. DA and MAO-B inhibitors may allow delay in starting L-dopa or allow lower doses of
L-dopa. Levodopa is combined with dopa-decarboxylase inhibitor such as Madopar. ‘modified-release’ has little benefit over
normal preps; dispersible tablets have rapid bioavailability & may help ‘jump-start’ pts in morning or during sudden ‘off’
freezing, SE: nausea & vomiting can be helped by domperidone; taking the pills with non-protein snack may help too (protein
↓effectiveness). Efficacy reduces with time, requiring larger & more frequent dosing, with worsening SE. in long-term,
dyskinesias, painful dystonias and response fluctuations such as unpredictable ‘off’ freezing & pronounced end-of-dose reduced
response are common problems(~50% at 6yrs). Non motor SE: psychosis; visual hallucinations. Dopamine agonists (DA):
Ropinirole and pramipexole monotherapy can delay starting L-dopa in early stages of PD, & allow lower doses of L-dopa as PD
progresses. Rotigotine transdermal patches available as mono or additive. SE: drowsiness, nausea, hallucinations, compulsive
behaviour (gambling, hypersexuality). Ergot-derived DA agonists (bromocriptine, pergolide, cabergoline) can cause heart
valvulopathy & serosal fibrosis & are not favoured. Amantadine (weak DA) used for drug-induced dyskinesias in late PD.
Apormorphine is a potent DA agonist used with continuous SC infusion to even out end-of dose effects or as rescue pen for
sudden ‘off’ freezing, SE: infection-site ulcers. Anticholinergics (e.g. benzhexol, orphenadrine) help tremor, but cause confusion
in elderly, SE: dry mouth, dizziness, vision ↓, urinary retention, pulse ↑, anxiety, confusion, excitement, hallucinations,
insomnias, memory ↓. MAO-B inhibitors (e.g. rasagiline, selegiline) are an alternative to dopamine agonists in early PD, SE:
postural hypotension and AF. COMT inhibitors: (e.g. entacapone, tolcapone) may lessen the ‘off’ time in those with end-of-dose
wearing off. Tolcapone has better efficacy, but may cause severe hepatic complications & requires close monitoring of LFT.
 Idiopathic PD continued…

Px: Neuropsychiatric complications such as depression, dementia and psychosis, are

common & may reflect disease progression or drugs SE. try SSRIs for depression.
Distinguish drug-induced psychosis (consider reducing DA-agonist doses) from disease
progression (try atypical antipsychotics e.g. quetiapine, olanzapine). Respite care is
much valued by carers in advanced disease. Deep brain stimulation (DBS) may help
those who are partly dopamine-responsive. Surgical ablation of overactive basal
ganglia circuits. Is Parkinson’s plus syndrome present? 5 VIVID red flags: 1) early
postural instability and vertical gaze palsy +/- falls; rigidity of trunk> in limbs;
symmetrical onset; speech & swallowing problems; little tremor -> progressive
supranuclear palsy. 2) early autonomic features e.g. impotence/incontinence, postural
↓BP; cerebellar + pyramidal signs; rigidity > tremor -> multiple system atrophy. 3)
fluctuating cognition with visual hallucination & early dementia-> Lewy body
dementia. 4) Akinetic rigidity involving one limb; cortical sensory loss, apraxia (even
autonomous interfering activity by affected limb- the ‘alien limb’ phenomenon->
cortico-basal degeneration (CBD). 5) pyramidal signs (legs) e.g. in diabetic/hypertensive
pt who falls or has gait problems e.g. ataxia (no fenestration) -> vascular parkinsonism
(2-5% of ‘PD’).
 Thyrotoxicosis (hyperthyroidism)

Clinical effect of excess thyroid hormone, usually from gland hyperfunction. Symptoms: diarrhoea, weight ↓,
appetite ↑, (if ↑ ↑, paradoxical weight gain in 10%); over-active; sweats; heat intolerance; palpations; tremor;
irritability; labile emotions; oligomenorrhoea +/- infertility. Rarely psychosis; chorea; panic; itch; alopecia; urticarial.
Signs: pulse fast/irregular (AF or SVT; VT rare); warm moist skin; fine tremor; palmar erythema; thin hair; lid lag;
eyelid lags behind eyes descent as pt watches your finger descend slowly; eyelid retraction causing a staring
appearance; may be goitre; thyroid nodules or built depending on cause. Signs of graves: 1) eye disease:
exophthalmos, opthalmoplegia. 2) preorbital myxoedema: oedematous swellings above lateral malleoli 3) thyroid
acropachy: extreme manifestation, with clubbing, painful finger & toe swelling, and periosteal reaction to limb
bones. Tests: TSH ↓(supressed), T4 and T3 ↑. May be mild normocytic anaemia, mild neutropenia, ESR ↑, Ca2+ ↑,
LFT ↑. Also: check thyroid autoantibodies. Isotopoe scan if cause unclear, to detect nodular disease or subacute
thyroiditis. If opthalmopathy, tests VF’s, VA and eye movements. Causes: graves disease: prevalence: 0.5%.
Female:male 9:1. typical age: 40-60yrs (younger if maternal fam history). Cause: circulating IgG autoantibodies
binding to and activating G-protein-coupled thyrotropin receptors, which cause smooth thyroid enlargement and
↑hormone production (esp T3), and react with orbital autoantigens. Triggers: stress; infection; childbirth. Pts are
often hyperthyroid but may be/become hypo- or euthyroid. Associated with other autoimmune disease: vitiligo,
type 1 DM, addisons. Toxic multinodular goitre: seen in elderly and in iodine-deficient areas. There are nodules
that secrete thyroid hormones. Surgery is indicated for compressive symptoms from enlarged thyroid (dysphagia or
dyspnoea). Toxic adenoma: a solitary nodule producing T3 and T4. on isotope scan, the nodule is hot & rest of gland
is supressed. Ectopic thyroid tissue: mets follicular thyroid cancer, or struma ovarii: ovarian teratoma with thyroid
tissue. Exogenous: iodine excess e.g. food contamination, contrast media. Levothyroxine excess causes ↑T4, ↓T3,
↓thyroglobulin. Others: 1) subacute de Quervain’s thyroiditis: self-limiting post-viral with painful goitre, T ↑ +/-
ESR. Low isotope uptake on scan. Px: NSAIDs. 2) drugs: Amiodarone, lithium (hypothyroidism more common). 3)
Postpartum 4) TB (rare)
 Thyrotoxicosis continued…

Management: 1) drugs: B-blockers (e.g. propranolol) for rapid control of

symptoms. Anti-thyroid med: A) titration e.g. carbimazole for 4wks, reduce
according to TFTs every 1-2months. B) block-replace: give carbimazole +
thyroixine simultaneously (less-risk of iatrogenic hypothyroidism). In graves,
maintain on either regimen for 12-18m then withdraw~ 50% will relapse
requiring radioidine or surgery. Carbimazole, SE: agranulocytosis (↓
↓neutrophils, can lead to dangerous sepsis; rare); warn to stop & get urgent
FBC if signs of infection e.g. T ↑, sore throat/mouth ulcers. 2) Radioiodine
(i131): most become hypothyroid post-treatment. There is no evidence for
↑cancer, birth defects or infertility in women, CI: pregnancy, lactation. Caution
in active hyperthyroidism ask risk of thyroid storm. 3) Thyroidectomy: carries
risk of damage to recurrent laryngeal nerve (hoarse voice) and hypothyroidism.
Complications: HF (thyrotoxic cardiomyopathy, ↑in elderly), angina, AF (seen in
10-25%: control hyperthyroidism & warfarinize if no CI), osteoporosis,
opthalmopathy, gynaecomastia-> thyroid storm.
 Thyroid eye disease

Seen in 25-50% of people with graves disease. Main known risk factor is smoking. The eye disease may not
correlate with thyroid disease & pt can be euthyroid, hypothyroid or hyperthyroid at presentation. Eye
disease may be first presenting sign of Grave’s & can also be worsened by treatment, typically with
radioiodine (usually a transient effect). Retro- orbital inflammation and lymphocyte infiltration results in
swelling of orbit. Symptoms: eye discomfort, grittiness, tear production ↑, photophobia, diplopia, acuity ↓,
afferent pupillary defect may mean optic nerve compression-> seek expert advice at once as decompression
may be needed. Nerve damage does not necessarily go hand in hand with protrusion. Indeed, if eye cannot
protrude for anatomical reasons, optic nerve compression is more likely- a paradox! Signs: Exophthalmos-
appearance of protruding eye; proptosis- eyes protrude beyond orbit (look from above in same plane as
forehead); conjuntival oedema; corneal ulceration; papillodema; loss of colour vision. Opthalmoplegia (esp
of upward gaze) occurs due to muscle swelling and fibrosis. Tests: diagnosis is clinical. CT/MRI of orbits may
reveal enlarged eye muscles. Management: get specialist help. Treat hyper- hypothyroidism. Advise to stop
smoking as this worsens prognosis. Most have mild disease that can be treated symptomatically (artificial
tears, sunglasses, avoid dust, elevate bed when sleeping to ↓periorbital oedema). Diplopia can be
managed with a Fresnel prism stuck to one lens of a spectacle (aids easy changing as exophthalmous
changes). In more severe disease with opthalmoplegia or gross oedema, try high-dose steroids (IV
methylprednisolone better than PO prednisolone)- decreasing according to symptoms. Surgical
decompression is used for severe sight-threatening disease or for cosmetic reasons once activity of eye
disease has reduced. Eyelid surgery may improve comesis and function. Orbital radio can be used to treat
opthalmoplegia but has little effect on proptosis. Future options: Anti-TNFalpha (e.g. infliximab)
 Addisons disease (adrenal insufficiency)

Anyone on exogenous steroids long enough to supress pituitary-adrenal axis, or who has overwhelming sepsis or has mets
cancer may suddenly develop adrenal insufficiency with deadly hypovolaemic shock. Primary adrenocortical insufficiency:
(addisons disease) is rare but can be fatal. Destruction of adrenal cortex leads to glucocorticoid (cortisol) and mineralocorticoid
(aldosterone) deficiency. You may diagnose a viral infection/anorexia nervosa in error (K+ is ↓in latter but ↑in addisons).
Cause: 80% are due to autoimmunity in UK. Other causes: TB (commonest cause worldwide), adrenal mets (e.g. from lung,
breast, renal CA), lymphoma, opportunistic infections in HIV; adrenal haemorrhage, congenital. Symptoms: often diagnosed
late, lean, tanned, tired, tearful +/- weakness, anorexia, dizzy, faints, flu-like myalgias/arthralgias. Mood: depression, psychosis,
low-self esteem. GI: nausea/vomiting, ab pain or vomiting. Pigmented palmar creases & buccal mucosa (↑ACTH; cross-reacts
with melanin receptors). Postural hypotension. Vitiligo. Shock, T ↑, coma. Tests: Na+ ↓ & K+ ↑ (due to ↓mineralocorticoid),
glucose ↓(due to ↓cortisol). Also: uraemia, Ca2+ ↑, eosinophilia, anaemia. Short ACTH stimulation test: do plasma cortisol
before and 0.5h after tetracosactide (Synacethen) IM. Addisons is excluded if 30m cortisol is >550nmol/L. steroid drugs may
interfere with assays: ask lab. NB: in pregnancy & pill, cortisol levels may be reassuring but falsely ↑, due to ↑cortisol-binding
globulin. Also ACTH: in addisons, 9AM ACTH is ↑. It is low in secondary causes. 21-Hydroxylase adrenal autoantibodies +ve in
autoimmune disease in >80%. Plasma renin & aldosterone for mineralocorticoid status. AXR/CXR: any past TB, e.g. upper zone
fibrosis or adrenal calcification? If no autoantibodies, consider further tests. Treatment: replace steroids: give hydrocortisone
daily. Avoid giving late (may cause insomnia). Mineralocorticoids to correct postural hypotension, K+ ↑, Na+ ↓:
fludrocortisone PO. Adjust both on clinical grounds. If poor response, suspect associated autoimmune disease. Steroid use:
warn against abruptly stopping steroids. Add extra hydrocortisone before stenous activity/exercise. Double steroids in febrile
illness, injury or stress. Give out syringes and in-date IM hydrocortisone- if vomiting prevents PO intake. Follow up: yearly (BP,
U&E); watch for autoimmune diseases (perinicious anaemia). Prognosis (treated): adrenal crisis & infections do cause excess
deaths: mean age at death for men ~65yrs (76 is normal estimated life expectancy) for women its higher. Secondary adrenal
insufficiency: commonest cause is iatrogenic, due to long-term steroid therapy leading to suppression of pituitary-adrenal axis-
only becomes apparent on withdrawal of steroids. Other causes are rare & include hypothalamic-pituitary disease leading to
↓ACTH production. Mineralocorticoid production remains intact, & there is no hyperpigmentation as ↓ACTH.
 Leu kaemia

These pts fall ill suddenly & deteriorate fast e.g. with: infection, bleeding (Px: platelets +/- FFP) and hyperviscosity. Take
nonspecific confusion/drowsiness or just “I feel a bit ill today” seriously (may be dead tomorrow): do blood cultures, glucose,
U&E,, LFT, Ca2+, and clotting. Consider CNS bleeding- CT/MRI if in doubt. Neutropenic regimen: full barrier nursing if possible.
Hand-washing is vital. Use a side room. Avoid IM injections (danger of infected haematoma). Look for infection (mouth, axilla,
pernium, IVI site). Take swabs. Check: FBC, platelets, INR, U&E, LFT, LDH, CRP. Take cultures; CXR if indicated. Wash pernium
after defection. Swab moist skin with chlorohexidine. Oral hygiene (e.g. with H2 peroxide) and Candida prophylaxis are
important. TPR (vital signs). High calorie diet; avoid foods with high risk of microbial contamination. Vases containing cut
flowers pose a Pseudomonas risk. Use of antibiotics in neutropenia: treat any known infection promptly. If T>38 or T >37.5 on 2
occasions, or 1h apart/pt toxic, assume septicaemia and start blind combo therapy- e.g. piperacillin-tazobactam (+ vancomycin,
if gram +ve organisms suspected or isolated e.g. hickman line sepsis). If fever persists despite antibiotics, think of CMV, fungi
(e.g. candida, Aspergillus and central line infection). Consider treatment for Pneumocystis, e.g. co-trimoxazole i.e trimethoprim
+ sulfamethoxazole PO/IV. remember TB. Other dangers: Tumour lysis syndrome: caused by massive destruction of cells to K+
↑, urate ↑ and renal injury. risk ↑if: LDH ↑, creatinine ↑, urate ↑, WCC ↑. Prevention: high fluid intake + allopurinol pre-
cytotoxics. For those at high risk of cell lysis, recombinant uricase (rasburicase) may be given. Hyperviscosity: if WCC high, WBC
thrombi may form in brain, lung and heart (leukostasis). Avoid transfusing before lowering WCC e.g. with hydroxycarbamide or
leukopheresis, as viscosity rises (risk of leukostasis ↑). DIC: widespread activation of coagulation, from release of procoagulants
into circulation with consumption of clotting factors and platelets with ↑risk of bleeding. Fibrin strands fill small vessels,
haemolysing passing RBCs, and fibrinolysis is also activated. Causes: malignancy, sepsis, trauma, obstetric events: OCHs. Signs:
bruising, bleeding anywhere (e.g. venepuncture sites), renal failure. Tests: platelets ↓, PT ↑, APTT ↑, fibrinogen ↓(correlates
with severity); fibrin degraduation products (D-dimers) ↑ ↑. Film: broken RBCs (schistocytes). Px: treat cause. Replace
platelets if low, cryoprecipitate to replace fibrinogen, FFP to replace coagulation factors. Activated protein C reduces mortality
in DIC with severe sepsis or multi-organ failure. Use of all-transretoinoic acid (ATRA) has significantly reduced risk of DIC in
acute pro-myelocytic leukaemia (commonest leukaemia associated with DIC). Preventing sepsis: Fluoroquinolone (e.g.
ciprofloxacin) before neutropenia gets serious. Herpes, pneumocystis and CMV (valganiclovir) prophylaxis have a role.
 Acute lymphoblastic leukaemia (ALL)

This is a maliginancy of lymphoid cells, affecting B or T lymphocyte cell lines, arresting maturation & promoting uncontrolled proliferation of
immature blast cells, with marrow failure & tissue infiltration. It is thought to develop from a combo of genetic susceptibility (e.g. with
translocations, and gains and losses of whole chromosomes) + environmental trigger. Ionizing radiation e.g. X-rays, during pregnancy, and
Downs are important associations. It is the commonest cancer of childhood, and is rare in adults. CNS involvement most common.
Classification is based on 3 systems: 1) Morphological. The FAB system (French, American, british) divides ALL into 3 types (L1, L2, L3) by
microscopic appeareance. Provides limited info. 2) immunological surface markers are used to classify ALL into: precursor B-cell ALL, T-cell
ALL, B-cell ALL. 3) Cytogenic chromosomal analysis. Abnormalities are detected in up to 85%, which are often translocations. Useful for
predicting prognosis, e.g. poor with Philadelphia (Ph) chromosome (below), and for detecting disease recurrence. Signs & symptoms:
Marrow failure: Anaemia(↓Hb), infection (WCC ↓) and bleeding (↓platelets). Infiltration: Hepato-splenomegaly, lymphadenopathy-
superficial or mediastinal, orchidomegaly, CNS involvement- e.g. cranial nerve palsies, meningism. Common infections: esp chest, mouth,
perianal and skin. Bacterial septicaemia, zoster, CMV, measlres, Candidiasis, Pneumocystis pneumonia. Tests: characteristic blast cells on
blood film and bone marrow. WCC usually high. CXR and CT scan to look for mediastinal and abd lymphadenopathy. Lumbar puncture should
be performed to look for CNS involvement. Treatment: support: blood/platelet transfusion, IV fluids, allopurinol (prevents tumour lysis
synd). Insert a subcutaneous port system/Hickman line for IV access. Infections: dangerous, due to neutropenia caused by disease and
treatment. Immediate IV antibiotics for infection. Start neutropenic regimen: prophylactic antivirals, antifungals and antibiotics e.g. co-
trimoxazole to prevent Pneumocystis pneumonia, but beware: can worsen neutropenia. Chemo: remission induction: e.g. vincristine,
prednisolone, L-asparaginase + daunorubicin. Consolidation: high-medium-dose therapy. CNS prophylaxis: Intrathecal (or high-dose IV)
methotrexate +/- CNS irradiation. Maintenance: pro-longed chemo: mercaptopurine, methotrexate, vincristine + prednisolone. Relapse is
common in blood, CNS, or testis (examine at follow up). Matched-related allogenic marrow transplants: once in 1st remission is best opt in
younger pts (too many SE if older?) Haematlogical remission: means no evidence of leukaemia in blood, normal/recovering blood count &
<5% blasts in regenerating marrow. Prognosis: cure rates for children are 70-90%; for adults only 40% (higher when imatinib/rituximab
used). Poor prognosis if: adult, male, Philadelphia chromosome: BCR-ABL gene fusion due to translocation of chromosomes 9 and 22
presents with CNS signs, Hb ↓ or high WCC or B-cell ALL. PCR used to detect minimal residual disease, undetectable by standard means.
Prognosis is poor if seen in high amounts at presentation or during remission. Prognosis in relapsed Ph-neg ALL is poor (improvable by
marrow transplant). Personalised treatment: tailor therapy to exact gene defect. Monoclonal antibodies gene-targeted retinoids, cytokines,
vaccines and T-cell infusions are relevant here. Biomarkers e.g. thiopurine methyltransferase, can predict toxicity from thiopurines.
 Acute myeloid leukaemia (AML)

Neoplastic proliferation of blast cells derived from marrow myeloid elements- progresses rapidly
(death in ~2m if untreated; ~20% 3yr survival after Px). Incidence: commonest acute leukaemia of
adults- increases with age. AML can be a long-term complication of chemo e.g. lymphoma. Also
associated with myelodysplastic states, radiation and syndromes e.g. Downs. Morphological
classification: there is much heterogeneity. 1) AML with recurrent genetic abnormalities 2) AML
multilineage dysplasia (e.g. 2degree pre-existing myelodysplastic synd) 3) AML, therapy related. 4)
AML, other 5) Acute leukaemias of ambiguous lineage (both myeloid and lymphoid phenotype).
Symptoms: marrow failure: symptoms of anaemia, infection or bleeding. DIC occurs in acute
promyelocytic leukaemia, a subtype of AML, where there is release of thromboplastin. Use of all-
transretintoic acid with chemo ↓risk of DIC. Infiltration: Hepatomegaly and splenomegaly, gum
hypertrophy skin involvement. CNS involvement at presentation is rare in AML. Diagnosis: WCC is
often ↑, but can be normal or even low. Blast cells may be a few in peripheral blood, so diagnosis
depends on bone marrow biopsy. Differentation from ALL may be by microscopy (Aeur rods are
diagnostic of AML), but is now based on immunophenotyping and molecular methods.
Complications: infection is a major problem= may be bacterial/fungal/viral and prophylaxis is given
for each during therapy. Pitfalls: AML itself causes fever, common organisms present oddly, few
antibodies are made, rare organsisms- particularly fungi (esp Candida or Aspergillus). Chemo causes
↑plasma urate levels (from tumour lysis)- so give allopurinol with chemo, and keep well hydrated
with IV fluids, leukostasis may occur if WCC ↑ ↑.
 Acute myeloid leukaemia (AML) continued…

Treatment: supportive: as for ALL walking exercises can relieve fatigue. Chemo: is very
intensive resulting in long periods of marrow suppression with neutropenia + platelets ↓.
Main drugs used include daunorubicin and cytarabine, with ~5% cycles given in 1w
blocks to get remission. Bone marrow transplant (BMT): pluripotent haematopoietic
stem cells are collected from marrow. Allogenic transplants from HLA-matched siblings or
matched unrelated donors are indicated during 1 st remission in disease with poor
prognosis. The idea is to destroy leukaemic cells & immune system by cyclophosphamide
+ total body irradiation, and then repopulate marrow by transplant from a matched
donor IV infused. BMT allows most intensive chemo regimens because marrow
suppression is not an issue. Ciclosporin +/- methotrexate are used to reduce effect of
new marrow attacking pts body. Complications: Graft Vs Host disease (may help explain
curative effect of BMT); opportunistic infections; relapse of leukaemia; infertility.
Prognosis: lower relapse rates ~60% long-term survivors, but significant mortality~10%.
Autologous BMT where stem cells are taken from pt themselves, is used in intermediate
prognosis disease, although some studies suggest better survival rates with intensive
chemo regimens. Autlogous mobilized peripheral blood stem cell transplant may offer
haemopoietic recovery & less morbidity. Supportive care, or lower dose chemo for
disease control may be more appropriate in elderly pts where intensive therapies have
 Myelodysplastic syndromes (MDS, myelodysplasia)

These are hetrogenous group of disorders that manifest as marrow failure with risk
of life-threatening infection & bleeding. Most are primary disorders, but may also
develop secondary to chemo or radio. 30% transform to leukaemia. Tests:
Pancytopenia, with ↓reticulocyte count. Marrow cellularity is usually increased
due to ineffective haematopoiesis. Ring sideroblasts may also be seen in marrow.
There are different subtypes, grouped according to WHO classifications.
Treatment: multiple transfusions of red cells or platelets as needed. EPO +/-
human granulocyte colony stimulating factor (G-CSF) may lower transfusion
requirement. Immunosuppressives are also used, e.g. ciclosporin or
antithymocyte globuilins. Curative aloogenic stem cell transplantation is one opt-
often inappropriate owing to age-related comorbidities- most are >70yo.
Thalidomide analogues such as lenalidomide have a role e.g. in low risk MDS with
5q deletions. Hypomethylating agents (e.g. azacytidine and decitabine) have a
role in symptomatic MDS (target epigenetic changes). Prognosis: median survival:
from 6m to 6yr according to disease type.
 Chronic myeloid leukaemia (CML)

CML characterized by an uncontrolled clonal proliferation of myeloid cells- accounts from 15% of leukaemias. It is a
myeloproliferative disorder having features in common with these diseases e.g. splenomegaly. Occurs most often between
40-60yrs with a slight male predominance and rare in childhood. Philadelphia chromosome: (Ph) present in >80% of those
with CML. It is a hybrid chromosome comprising reciprocal translocation between long arm of chromosome 9 and 22-t-
forming a fusion gene BCR/ABL on chromosome 22, which has tyrosine activity. Those without Ph have a worse prognosis.
Some pts have a masked translocation- cytogenetics do not show the Ph, but rearrangement is detectable by molecular
techniques. Symptoms: mostly chronic and insidious: weight ↓, tiredness, fever, sweats. There may be features of gout
(due to purine breakdown), bleeding (platelet dysfunction), and ab discomfort (splenic enlargement). ~30% are detected by
chance. Signs: splenomegaly (>75%)- often massive. Hepatomegaly, anaemia, bruising. Tests: WBC ↑ ↑with whole
spectrum of myeloid cells, i.e ↑neutrophils, myelocytes, basophils, eosinophils. Hb ↓or normal, platelets variable. urate ↑,
B12 ↑. Neutrophil alk phos score ↓. Bone marrow is hypercellular. Ph found on cytogenic analysis of blood or bone
marrow. Natural history: variable, median survival 5-6yrs. 3 phases: Chronic, lasting a few months/yrs -> accelerated phase,
with increasing symptoms, spleen size and difficulty in controlling counts-> blast transformation, with features of acute
leukaemia +/- death. Treatment: Imatinib, a specific BCR-ABL tyrosine kinase inhibitor, which has transformed therapy
over last 10yrs. More potent 2nd generation BCR-ABL inhibitors: dasatinib, nilotinib, bosutinib and ponatinib. Dasatinib and
nilotinib allow more pts to achieve deeper, more rapid responses associated with improved outcomes. Imatinib SE: usually
mild: nausea, cramps, oedema, rash, headache, arthralgia. May cause myelosupression. Dasatinib has been used in
imatinib-resistant blast crises. Hydroxycarbamide is also used. Those with lymphopblastic transformation may benefit from
treatment as for ALL. Treatment of myeloblastic transformation with chemo rarely achieves lasting remission, and allogenic
transplantation offers best hope. Stem cell transplant: allogenic transplant from an HLA-matched sibling or unrelated donor
offers the only cure, but carries significant morbidity and mortality. Guidelines suggest that this approach should be used 1 st
line only in young where mortality rates are lower. Other pts should be offered imtatinib. Pts are reviewed annually to
decide whether to continue imatinib or to offer combo therapy or stem cell transplant.
  
Hodgkin’s lymphoma

Lymphomas are disorders caused by maliginant proliferations of lymphocytes. These accumulate in lymph nodes causing
lymphadenopathy, but may also be found in peripheral blood or infiltrate organs. Lymphomas are histologically divided into
Hodgekins and non-Hodgekin’s types. In Hodgekin’s lymphoma, characteristic cells with mirror-image nuclei are found, called
Reed-Sternberg cells. Incidence: 2 peaks of incidence: young adults and elderly. Male:female 2:1. risk ↑ if: affected sibling, EBV,
SLE, post-transplant; westernisation; obese. Symptoms: often presents with enlarged, painless, non-tender, ‘rubbery’ superficial
lymph nodes, typically cervical (60-70%), also axillary or inguinal nodes. Node size may increase/decrease spontaneously, and
nodes, pruritus and lethargy. There may be alcohol-induced lymph node pain. Mediastinal lymph node involvement can cause
features due to mass effect, e.g. bronchial or SVC obstruction, direct extension e.g. causing pleural effusions. Pel-Ebstein fever
implies a cyclical fever with long periods of normal/low temp- rare. Signs: lymph node enlargement. Also, cachexia, anaemia,
spleno/hepato-megaly. Tests: tissue diagnosis: lymph node excision biopsy if possible- image-guided needle biopsy, laparotomy or
mediastinoscopy may be needed to obtain a sample. Bloods: FBC, film, ESR, LFT, LDH, urate, Ca2+. ↑ESR or ↓Hb indicate worse
prognosis. LDH is ↑as its released during cell turnover. Staging: done by CXR, CT/PET of thorax, abdo, pelvis +/- marrow biopsy if B
symptoms or stage 3-4 disease. 1) confined to single lymph node region 2) involvement of 2+ nodal areas on same side of
diaphragm 3) involvement of nodes on both sides of diaphragm 4) spread beyond lymph nodes e.g. liver/marrow. Each stage is
either ‘A’ no systemic symptoms other than pruritus; or ‘B’- presence of B symptoms: weight loss >10% in last 6m, unexplained
fever >38/night sweats (needing change of clothes). ‘B’ indicates worse disease. Localised extra-nodal extension does not advance
the stage but indicated by ‘E’. Chemo-radio- therapy: radio +/- short courses of chemo for stages 1-A and 2-A. longer courses of
chemo for 2-A with >3 areas involved through to 4-B. ‘ABVD’: Adriamycin, Bleomycin, Vinblastine, Dacarbazine (+ radio in younger
pts) cures ~80% of pts. More intensive regimens are used if poor prognosis or advanced disease. In relapsed disease, high-dose
chemo with peripheral stem-cell transplants may be used, involving autologous (or occasionally allogenic) transplant of peripheral
blood progenitor cells to restore marrow function after therapy. Complications of treatment: Radio may ↑risk of second
malignancies- solid tumours (esp lung, breast, melanoma, sarcoma, stomach & thyroid cancers), ischaemic heart disease,
hypothyroidism & lung fibrosis due to radiation field. Chemo SE: myelosupression, nausea, alopecia, infection. AML, non-
hodgekins lymphoma & infertility mau be due to both chemo/radio. 5 yr survival: depends on stage & grade >95% in 1-A
lymphocyte-predominant disease; <40% with 4-B lymphocyte- depleted. Emergency presentations: infection; SVC obstruction-
JVP ↑, sensation fullness in head, dyspnoea, blackouts, facial oedema.
 Non- Hodgekins lymphoma

Includes all lymphomas without Reed-Sternberg cells- a diverse group. Most derived from B-cell lines; diffuse large B-cell lymphoma
(DLBCL) is commonest. Not all centre on nodes (extranodal tissues generating lymphoma include mucosa-associated lymphoid tissue
e.g. gastric MALT). Incidence doubled since 1970. causes: Immunodeficiency- drugs; HIV; (usually high-grade lymphoma from EBV
transformed cells); HTVL; H-Pylori; toxins; congenital. The pt: nodal disease (75% at presentation): superficial lymphadenopathy. Extra-
nodal disease (25%)- Skin: T-cell lymphomas: Sezary syndrome. Oropharynx: Waldeyer’s ring lymphoma causes sore throat/obstructed
breathing. Gut: 1) Gastric MALT caused by H-pylori & may regress with its eradication. Symptoms: Like gastric CA, with systemic
features (fever, sweats). MALT usually involves the antrum, is multi-focal and mets late. 2) Non-MALT gastric lymphomas (60%) are
usually diffuse large-cell B lymphomas- high-grade and not responding well to H-pylori eradication. 3) small-bowel lymphomas are
IPSID (immunoproliferative small intestine disease), MALT or enteropathy/celiac-associated intra-epithelial T-cell lymphoma presents
with diarrhoea, vomiting and ab pain, and weight ↓. Poor prognosis. Other possible sites: Bone, CNS and lung. Systemic symptoms-
fever, night sweats, weight loss (less common than in Hodgekin’s lymphoma, and indicates disseminated disease). Pancytopenia from
marrow involvement- anaemia, infection, bleeding (↓platelets). Tests: Blood: FBC, U&E, LFT. ↑LDH~worse prognosis, reflecting ↑cell
turnover. Marrow & node biopsy for classification. Staging Ann Arbor system- CT/MRI of chest/ab/pelvis. Send cytology of any
effusion; LP for CSF cytology if CNS signs. Diagnosis/management is MDT. Low-grade lymphomas are indolent, often incurable &
widely disseminated. Include: follicular lymphoma, marginal zone lymphoma/MALT, lymphocytic lymphoma (closely related to CLL &
treated similarly), lymphoplasmacytoid lymphoma (produces IgM= Waldenstroms macroglobulinaemia). High-grade lymphomas are
more aggressive, but often curable. Often rapidly enlarged lymphadenopathy with systemic symptoms. Include: Burkitts lymohoma
(childhood disease with characteristic jaw lymphadenopathy; lymphoblastic lymphomas (like ALL), diffuse large-B-cell lymphoma.
Treatment: depends on disease subtype. Low grade: if symptomless, none may be needed. Radio may be curative in localised disease.
Chlorambucil is used in diffuse disease. Remission may be maintained by using alpha-interferon or rituximab. Bendamustine is
effective both with rituximab & as a monotherapy in rituximab-refractory pts. High grade: (e.g. large B-cell lymphoma, DLBCL) ‘R-
CHOP’ regimen: Rituximab, Cyclophosphamide, Hydroxydaunorubicin, vincristine (Oncovin) and Prednisolone. Granulocyte colony-
stimulating factors (G-CSF) help neutropenia- e.g. filgrastim or lenograstim. Survival: histology important. Prognosis worse if at
presentation. Age >60yrs, systemic symptoms, Bulky disease (ab mass >10cm) ↑LDH, disseminated disease. Typical 5yr survival for
treated pts~30% for high-grade and >50% for low-grade lymphomas but picture is very variable.
 Delirium

20% of elderly pts on medical/surgical wards have some form of delirium. Consider any acute fluctuating
baffling behaviour change as possible delirium. Look for organic causes (UTI, pneumonia, MI). 8 signs of
delirum: Disordered thinking: slow, irrational, rambling, jumbled up, incoherent ideas. Euophoric, fearful,
depressed or angry: labile mood, e.g. anxious then torpid. Language impaired: speech reduced or
gabbling, repetitive and distruptive. Illusions/delusions/hallucinations: tactile or visual (auditory suggest
psychosis). Reversal of sleep-awake cycle: may be drowsy by day and hypervigilant at night. Inattention:
focusing, sustaining or shifting attention is poor; no real dialogue. Unaware/disorientated: doesn’t know
its evening, or hi own name or location. Memory deficits: often marked. (later he may be amnesic for the
episode). Summary: globally impaired cognition and awareness/consciousness. Causes: systemic
infection, intracranial infection, drugs, alcohol/drug withdrawal, metabolic, hypoxia, vascular, head injury,
epilepsy, nutritional. Differentials: if agited is it anxiety? Check conscious level. If delusions or
halcinations, is it a primary mental illness (e.g. skitz)- but rare on wards esp if no past history & delirium is
v common in ill pts. Tests: consider FBC, U&E, LFT, blood glucose, ABG, septic screen (urine dipstick, CXR,
blood cultures); also ECG, malaria films, LP, EEG, CT/MRI. Management: after ID & treating underlining
cause: reduce distress & prevent accidents, nurse in a moderately lit, quiet room ideally with same staff to
reduce confusion where pt can be watched, do not use physical restraints- remove catheters & other
impedimenta, augment-self-care, use 3m non drug cures for agitation: music, massage and muscle
relaxation. Minimise meds (esp sedatives) but if distruptive then some sedation e.g. PO
haloperidol/chloropromazine, IM if not- wait 20m to judge effect then further dose if needed. Avoid
achloropromazine in alcohol withdrawal and elderly. Delirium may persist beyond duration of original
illness.
 Alcoholism

Management for withdrawal: give chlorodiazpoxide for a few days then slowly
wean off, alternative: diazepam.
 HIV

HIV1 a retrovirus is responsible for most HIV infections. HIV2 causes a similar illness (longer latent period). Over 30m
people are HIV +ve (Africa has 25%). There is increasing HIV transmission in eastern Europe & middle easy, where
homosexuality is less accepted. Male:female 3:1. Immunology: HIV binds via its gp120 envelope glycoprotein to CD4
receptors on helper T lymphocytes, monocytes, macrophages and neural cells. CD4 +ve cells migrate lymphoid tissue
where virus replicates, producing billions of new virions. These are released and in turn infect new CD4 +ve cells. As
infection progresses depletion or impaired function of CD4 +ve cells ↓immune function. Virology: RNA retrovirus; HIV1
has 9subtypes or ‘clades’. After cell entry, viral reverse transcriptase enzyme makes DNA copy of RNA genome. Viral
integrase enzyme them integrates this into host DNA. Core viral proteins are initially synthesised as big polypeptides that
are cleaved by viral protease enzymes into enzymes & building blocks of virus. The completed virions are then released by
budding. The number of circulating viruses (viral load) predicts progression to AIDs. Stages: seroconversion (primary
infection) may be accompanied by transient illness 2-6w after exposure: fever, malaise, myalgia, pharyngitis,
maculopapular rash or meningoencephalitis (rare). A period of asymptomatic infection follows but 30% have persistent
generalised lymphadenopathy (PGL), defined as nodes >1cm diameter at >2 extra-inguinal sites, persisting for 3m or
longer. Later, constitutional symptoms develop: T ↑, night sweats, diarrhoea, weight ↓, +/- minor opportunistic infections
e.g. oral candida/hairy leucoplakia, herpes zoster, recurrent herpes simplex, seborrhoeic dermatitis, tinea- this collection
of symptoms & signs is referred to as AIDS-related complex (ARC) and is regarded as a prodrome to AIDS. AIDS: HIV + an
indicator disease. CD4 usually low. Diagnosis: serum (or salivary) HIV-Ab by ELISA e.g. confirmed by western blot. In recent
infection, HIV-Ab might be –ve (window period ~1-3w after exposure); here, checking HIV RNA (PCR) or core p24 antigen
in plasma, or repeating ELISA at 6w and 3m confirms diagnosis. HIV subtypes: A and B predominate in UK; D is commoner
in Africa; hybrid/recombo types have a worse prognosis as they bind to immune cells more readily. Prevention: blood
screening; disposable equipment; antenatal antiretovirals if HIV +ve +/- C birth +/- bottle-feeding (may ↑mortality if
hygiene poor); PEP. A stop-HIV sexual manifesto: Good HIV info, accessable HIV tests, condoms for all sexual contacts,
fewer sexual partners, ↓alcohol use. Good trials find circumcision prevents ~65% of HIV and herpes although not reliable.
 HIV continued… (complications)

Most complications are either psychological or result of suppression of T-cell mediated immunity-> test all with newly diagnosed
HIV for toxoplasma, CMV, hepatitis B/C & syphilis e.g. serology; tuberculin test. Pulmonary: lung is most vulnerable organ; in
developed countries bacterial pneumonia (pneuomoccal) is commonest; elsewhere its TB and Pneumocystis jiroveci pneumonia-
the chief life threatening fungal opportunistic infection- suspect it anyone with cough/breathlessness or pneumothorax. CXR may
be normal; CT: diffuse ground-glass opacity, consolidation, nodules, cysts. Test: sputum. Px: high-dose co-trimoxazole, precede
each dose by prednisolone (reduce after few days then tail off). Primary prophylaxis: if CD4 low give PO co-trimoxazole until
normal. Other pathogens: M.avium intracellulare (MAI); CMV. Also: HHV-8 (Kaposi’s sarcoma, lymphoma) and lymphoid
interstitial pneumonitis. Gut: oral pain may be caused by candidiasis, HSV or aphthous ulcers, or tumours. Oral candida Px:
Nystatin suspension. Oesphageal involvement causes dysphagia +/- retrosternal discomfort- Px: PO fluconazole, ketoconazole or
itraconazole-relapse common. HSV and CMV also cause oesophageal ulcers. Anorexia/weight loss: is common, also LFT ↑ and
hepatomegaly from viral hepatitis, sclerosing cholangitis, drugs or MAI. MAI causes fever, night sweats, malaise, anorexia,
↓weight, ab pain, diarrhoea, hepatomegaly and anaemia. Tests: blood cultures, biopsies (lymph node, liver, colon, bone
marrow). Px: ethambutol + clarithromycin + rifabutin. Chronic diarrhoea may be caused by bacteria, protozoa, microsporidium,
Isospora belli, cyclospora or viruses. Perianal disease may be from recurrent HSV ulceration, perianal warts, squamous cell
cancer (rare). Kaposi’s sarcoma and lymphomas can also affect gut. Eye: CMV retinitis (acuity ↓+/- blindness) may affect 45% of
those with AIDS. Fundoscopy: characteristic ‘mozzarella pizza’ signs. Treatment: induction: ganciclovir eye implant. PO
Valganciclovir or cidofovir: start with IV. CNS: acute HIV is associated with transient meningoencephalitis, myelopathy and
neuropathy. Chronic HIV-associated neurocognitive disorder (HAND) comprises dementia and various encephalopathies.
Toxoplasma gondii is main CNS pathogen in AIDS presenting with focal signs (impaired neuro signs). CT/MRI shows ring shaped
contrast enhancing lesions. Treat with pyrimethamine (+folinic acid) + sulfadiazine or clindamycin. Lifelong secondary
prophylaxis needed. Pneumocystis prophylaxis also protects against toxoplasmosis. Cryptococcus neoformans causes a chronic
meningitis e.g. with no neck stiffness. Test: India ink stain; CSF culture; cryptococcal antigen in blood & CSF. Px: IV Amphotericin
B + 5-flucytosine. 20% mortaliy- normalising ICP may help. Give secondary prophylaxis (fluconazole). Psychlogical complications:
HIV is 100% preventable but very prevelant. Why? – shame, sexual imperatives, pride and prejudice, keep HIV underground- e.g.
imagine you are HIV +ve and preg as a result of rape.
 HIV continued… (essentials)

Get comfy talking about sex. NB: asking are you gay? Isnt helpful. If speaking to a man, ask about sex with other men as many wont
ID themselves as gay (esp in repressive countries). Globally, men who have sex with other men have 19-fold risk of HIV from others.
Preventing HIV depends on us all promoting lifelong safer sex condoms, fewer partners & regular testing (esp where HIV rates ↑).
Videos + interactive discussions can double condom use. Warn everyone about dangers of sexual tourism/promiscuity. Teacher skills
in sexual negotiation. Explain how alcohol can undermine safe sex messages. Promote human rights so groups driving spread of HIV
aren’t driven underground. Introduce drug users to needle exchange schemes. Promote work of STI clinics. Good control of other
STIs ↓HIV incidence by 40%. Encourage HIV testing e.g. in pregnancy (+/- C section if +ve). Diagnose HIV early: have high index of
suspicion in all with TB, pneumonia, diarrhoea, meningitis, weight ↓, lymphoma, severe fungal infections or candida. Pre/post
exposure prophylaxis (PReP/PEP): follow guidelines & know drug locations. Seroconversion post-needle-stick ~0.4% for HIV and
30% for Hep B if HBeAg +ve. Wash well- if needle stick, encourage bleeding no sucking or immersing in bleach. Note name, address
and clinical details of donor. Report incident to occ health & fill in accident form. Store blood from both parties (HIV, HBV, HCV
tests). Immunise (active & passive) against Hep B at once if needed. Counsel & test recepients at 3 & 6m. Weigh risks by questioning
donor; if HIV+ve, what is CD4 and viral load count? Before prophylaxis do pregnancy test- was inoculum big? Was injury deep? Start
PEP incase of significant exposure to blood or high-risk fluid from HIV+ve source or any source with ↑risk. PEP is not indicated after
low risk exposures (e.g. urine, vomit, salima, faeces, unless visibly blood-stained). Start PEP asap (within 48-72h) PEP not needed if
exposure >72h ago. Do follow up testing at 12 and 24w & continue for >12w after HIV exposure event. Starter regimen: one
truvada tab (tenofovir & emtricitabine) + kaltera tabs (lopinavir & ritonavir) if cannot take truvada. Acute seroconversion: early ID
matters! Signs are like infectious mononucleosis (e.g. lymphadenopathy, myalgia, rash, headache; rarely meningitis); do tests if
unusual signs e.g. oral candidiasis, recurrent shingles, leucopenia or CNS signs (antibody tests may be –ve but viral antigen & HIV
RNA levels ↑in early infection). Take thorough history, advise against unambigious transmission. Other direct effects of HIV:
Osteoporosis; dementia (brain sancturary for HIV and HAART may not prevent dementia from developing). When seeing HIV+ve
people ask: have you been to STD clinic? Use condoms? Share needles? Have you told your partners? What is your CD4 count/HIV-1
RNA level? Viral load helps plan start of antiretrovirals; prompt prophylaxis for pneumocystis, toxoplasma, and MAC, respectively.
Whats your CMV & toxoplasma titre (counsel to avoid infection, e.g. no undercooked meat, avoid cats). Recent CXR? (e.g. TB,
pneumocystosis). Last cervical smear? (risk of neoplasia ↑). Are you a sad/depressed person?
 Antiretroviral agents

1) Drug interactions important so be careful 2) any new sign in pt can be SE or effect of HIV 3) know baseline
viral load 4) monitor: BP, U&E, glucose/lipids- HAART may cause renal failure +/- insulin resistance. Nucleoside
reverse transcriptase inhibitors (NRTI): Zidovudine (AZT) was 1st line, PO/IV, SE: anaemia, WCC ↓, GI
disturbance, fever, rash, myalgia. Stop if ↑LFT, hepatomegaly, lactic acidosis. CI: anaemia, neutropenia,
breastfeeding. Didanosine (DDI, Videx EC): PO, SE: pancreaitis, neuropathy, ↑urate, GI disturbance, retinal &
optic nerve changes, liver failure, stop if significant rise in LFT/amylase, CI: breastfeeding. Lamivudine (3TC):
well tolerated. PO, take with food, SE: see zidovudine, but less common, stop if: ↑LFT; big liver; lactic acidosis;
pancreaititis. Emtricitabine (FTC): like lamivudine but also active against Hep B. Stavudine (D4T): PO, stop if
neuropathy or ↑LFT. Tenofovir: PO, SE: see lamivudine. Abacavir: PO, SE: hepatitis, lactic acidosis,
hypersensitivity syndrome (3-5%), rash, fever, vomiting; may be fatal if rechallenged. Protease inhibitors (PI)
slow cell to cell spread, & lengthen time to first clinical event. Pis often given with low-dose ritonavir which
appears to enhance drug levels. All Pis are metabolised by cytochrome P450 enzyme system so increase conc.
Of certain drugs by competitive inhibition of their metabolism. PIs can cause dyslipidaemia,
hyperglycaemia/insulin resistance. Lopinavir/ritonavir(Kaletra), PO, SE: see saquinavir. Saquinavir PO with
meal, SE: oral ulcers, paraesthesiae, myalgia, headache, dizziness, pruritus, rash, pancreaititis. Fosamprenavir;
Tipranavir; darunavir; atazanavir; indinavir. Non-nucleoside reverse transcriptase inhibitors (NRTI) these may
also interact with drugs metabolised by cytochrome P450 enzyme system. Nevirapine PO, resistance emerges
readily, SE: Stevens- Johnson syndrome, toxic epidermal necrolysis, hepatitis. Efavirenz PO, SE: rash, insomnia,
dizziness, avoid in pregnancy. Rilpivirine a new NNRTI- resistance may develop. Integrase strand transfer
inhibitors (InSTIs) Raltegravir; elvitegravir; dolutegravir may be combo with tenofovir lamivudine, SE: GI
upset, insomnia. CCR5 antagonists (cc-chemokine receptor 5) Maraviroc PO. Once a day tablets on an empty
stomach at night; those with InSTI may be best e.g. Kivexa/Epzicom= abacavir + lamivudine, may be given with
C. Diff is gram +ve ‘superbug’ whose spores are contagious (faecal-oral or from environment, where
spores can live for ages and are hard to eradicate).
Signs: T ↑; colic; mild diarrhoea- or serious bloody diarrhoea with systemic upset- CRP ↑ ↑, WCC ↑ ↑,
albumin ↓, & colitis (with yellow adherent plaques on inflamed non-ulcerated mucosa-
pseudomembrane) & multi-organ failure. Asymptomatic carriage: 1-3% of all adults (from broad
spectrum/IV antibiotic use).
Predictors of fulminant C.diff colitis: >70y, past C.diff injection; use of antiperistaltic drugs; Girotra’s triad:
1)increasing ab pain/distension & diarrhoea 2) leucocytosis>18,000 3) Haemodynamic instability.
Toxins: tissue culture, ELISA, and PCR help detect C.diff toxins (CDT). Some strains produce no toxin & are
non-pathogenic; most produce toxins A and B, some are hypervirulent e.g. NAP1/027.
Px: stop causative antibiotic. Treatment not usually needed if asmptomatic, if symptomatic give PO
metronidazole (PO vancomycin is better for severe disease)- urgent colectomy may be needed if toxic
megacolon, LDH ↑ or if deteriorating.
Recurrent disease: repeat metronidazole once only (overuse causes irreversible neuropathy). NB:
probiotics may prevent recurrences (Saccharomyces boulardii unless immunocomp or CVP line in-situ).
Administration of stools (via NGT or colonoscope) from healthy subjects may have a role.
Preventing spread: Meticulous cleaning, use of disposable gloves, not using rectal thermometers, hand-
washing and ward protocols (e.g. ‘bare below elbows’).