Cardiovascular

Question 1

How do you assess direction of polarisation and axis deviation on an ECG

Answer 1

R wave shows direction of polarisation, should increase V1-4 (S waves increase V1-3 then decrease)

Axis should be directed towards lead II (most positive deflection)
Left axis Leaves II and III (I only positive, aVF negative), Right axis Returns to II and III (I only negative, aVF positive)

Question 2

Describe the depolarisation of heart cells

Answer 2

HEART CELL DEPOLARISATION: SLOW ENTRY OF SODIUM IONS TO CAUSE MEMBRANE POTENTIAL TO RISE FROM -60 TO -40mV, SPONTANEOUS DEPOLARISATION, CALCIUM ENTER CAUSING STRONGER DEPOLARISATION TO +5mV, POTASSIUM CAUSES REPOLARISATION BACK TO -60mV (CALCIUM AND POTASSIUM CHANNELS CLOSE)

Question 3

What parts of the clotting process do different anticoagulants affect

Answer 3

(Platelet aggregation)
Aspirin inhibits COX-1 and therefore thromboxane A2, less activation and aggregation
P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor), reduce ADP, less activation and aggregation
(Coagulation cascade)
Warfarin inhibits vitamin K - reduces II, VII, IX, X
Heparins increase antithrombin, inactivates thrombin and Xa, thrombin means less conversion of fibrinogen
DOACs: majority direct and reversible inhibitors of Xa, dabigatran inhibits thrombin

Question 4

Decsribe CHA2DS2VASc

Answer 4

CHA2DS2VASc (stroke assessment): =2 anticoagulant (=1 for men consider)
Chronic HF, hypertension, age >75 - 2, diabetes, stroke / TIA - 2, vascular disease, age 65-75, sex category female
2 = 2% stroke risk per year

Question 5

Describe the presentation of angina / IHD

Answer 5

Chest pain - tight, stab/ belt/ heavy, middle of chest
May radiate to one or both arms, neck, jaw, teeth
Breathless, palpitations, presyncope (sensation you are going to faint)
Very exercise related

Question 6

How is IHD diagnosed and what investigations are used

Answer 6

Diagnosis usually entirely from history
Primary care: ECG, haemoglobin, lipid profile, glucose / HbA1c
CT coronary angiogram gold standard, contrast used, assess flow of coronary arteries
Determine if obstructive coronary artery disease. If left main stem or severe 3 vessel disease → coronary angiography
ECG - usually normal, may show ST depression, flat/ inverted T waves
Cardiac stress test (exercise or dobutamine), monitor with ECG, ST depression = late stage. Many patients unsuitable

Question 7

Describe the ECG changes in acute coronary syndrome

Answer 7

STEMI: ST elevation and new left bundle branch block (wide QRS, V1-6), hyperactive T waves, pathological Q waves

NSTEMI: ST depression and T wave inversion

Pathological Q waves present after 6h of symptoms in full thickness infarction

Specific arteries: left coronary - anterolateral (I, aVL, V3-6); LAD - anterior (V1-4); circumflex - lateral (I, aVL, V5-6); right coronary - inferior (II, III, aVF)

Unstable angina usually has normal ECG

Question 8

Describe the management of angina / IHD

Answer 8

Lifestyle advice
All patients aspirin (clopidogrel if contraindicated) and a statin, dual therapy with aspirin + clopidogrel / rivaroxaban in patients ACS or undergoing PCI

If required also antihypertensives (target 120-130) - ACE / BB / ARB; antidiabetic drugs

Symptom relief: GTN spray, beta blocker, calcium channel blocker, long acting nitrate

Surgery when medical not working, PCI and CABG

Question 9

Why are antiplatelets the main stay of treatment in acute coronary sundrome

Answer 9

When a thrombus forms in a fast flowing artery it is mainly formed by platelets

Question 10

What is the presentation of ACS

Answer 10

Acute chest pain lasting longer than 20 mins, at rest, ⅓ in bed at night
Can radiate to left arm, jaw, neck. Does not respond to GTN
Sweating, nausea, vomiting, breathless, palpitations, anxiety, sense of impending doom
Significant hypotension. brady/ tachycardia

Question 11

Describe the investigations for ACS

Answer 11

Immediate ECG, coronary angiography (within 12h)
Bloods: troponin, glucose, FBC, U+Es, (CRP + lipids)

Question 12

How is a STEMI acutely managed

Answer 12

300mg aspirin + prasugrel / clopidogrel, IV morphine, ondansetron (add O2 and IV GTN if required)
Assess if PCI suitable - within 12h of onset / 2h of when fibrinlysis could be given without contraindications (IV unfractioned heparin in surgery)
Otherwise thrombolysis with alteplase / tenecteplase

Question 13

How is risk of NSTEMI assessed

Answer 13

GRACE score: age, HR, systolic, creatinine, cardiac arrest at admission, ST deviation, abnormal cardiac enzymes, killip class (no CHF, rales / JVD, pulmonary oedema, cardiogenic shock)

Question 14

How are NSTEMIs acutely managed

Answer 14

Grace score
High risk: coronary angiography +- revascularisation, 300mg aspirin + prasugrel / clopidogrel. If required: O2, morphine, GTN, ondansetron, heparin (fondaparinux)
Low risk: same as above but surgery not required if 6m mortality below 3%

Question 15

How are patients managed following an MI

Answer 15

Echocardiogram to assess LV function, cardiac rehabilitation (lifestyle)
Secondary prevention - continue dual antiplatelet, ACE inhibitors / ARB, beta blockers / rate limiting CCB, statins. If HF: spironolactone + dapgliflozin

Question 16

Define heart failure

Answer 16

Heart failure is caused by a structural and/or functional abnormality that produces raised intracardiac pressures and/or inadequate cardiac output at rest and/or at exercise

Question 17

Describe the pathophysiology of heart failure

Answer 17

When drop in arterial pressure in aorta/ heart, baroreceptors activate sympathetic nervous system. In heart failure there is chronic activation, effect is diminished, cardiac output stops increasing

Impaired LV function leads to backlog of blood, LA / pulmonary veins have increased volume + pressure, fluid leaks out

Question 18

How do you investigate heart failure (what do they show)

Answer 18

Transthoracic echocardiogram, ECG, CXR, NT BNP blood test; also: troponin, FBC, U+Es, HbA1c, LFTs, TFTs, CRP
Exercise stress testing, (CT) coronary angiogram
NT-proBNP blood test increased, echocardiogram - chamber size, valvular disease, MI
<400pg/mL HF unlikely, 400-2000 transthoracic doppler + specialist within 6 weeks, >2000 within 2 weeks + poor prognosis
X ray (ABCDE): Alveolar oedema (batwing), Kerley B lines (horizontal - peripheral lungs), Cardiomegaly, Dilated upper lobe vessels, pleural Effusion (costophrenic blunting)
ECG - ischaemia, MI, LV hypertrophy

Question 19

How is heart failure classified

Answer 19

NYHA Classification: I - no limitation (asymptomatic), II - slight limitation, III - marked limitation (symptoms on minimal exertion), IV - inability to carry out physical activity

Question 20

How is heart failure managed

Answer 20

Treat cause, lifestyle (avoid large meals (workload, sodium - water retention), vaccination)

Management ABAL: ramipril (ACE) (evidence sacubitril / valsartan better), bisoprolol (BB), spironolactone (aldosterone antagonist), furosemide (loop)
Symptoms persist - specialist: amiodarone, digoxin, sacubitril + valsartan

Avoid ACE if valve pathology
Calcium channel blockers and dihydropyridines (nifedipine) avoided in reduced

Comprehensive therapy (abs vp): aldosterone antagonist + beta blocker + sacubitril-valsartan + dapagliflozin (SGLT2 inhibitor)

Preserved ejection fraction (specialist): dapagliflozin, furosemide if still fluid overload

Question 21

What are the causes of secondary hypertension

Answer 21

ROPED: renal disease, obesity, pregnancy induced / preeclampsia, endocrine, drugs
Most common causes: renal (CKD, renal artery stenosis, nephritis), sleep apnoea, coarctation of aorta

Question 22

How is hypertension managed including different demographics

Answer 22

ACD pathway - ACE inhibitor (or ARB), calcium channel blocker, diuretics (thiazides then loop)
Ramipril (candesartan), nifedipine, bendroflumethiazide (furosemide)
Beta blockers are not first line but consider in young people
If 55+ or Afro-Caribbean likely low renin, calcium channel blocker first and ARB instead of ACE
In diabetics: ACD no matter the age

Question 23

What causes supraventricular tachycardia and how does it present on ECG

Answer 23

Electrical signal reneters the atria from the ventricles, causes another depolarisation and repeats
Presents with narrow complex tachycardia (< 0.12s or 3 small squares) followed immediately by T wave, P waves usually buried by T waves. HR > 150

Question 24

How do atrial flutter, AV block and L / R BBB present on ECG

Answer 24

Atrial flutter - organised sawtooth waves, regular QRS, two P waves for every QRS

AV block - long PR, 1st - PR and QRS associated, 2nd slightly associated (Mobitz I PR progressively prolonged until dropped, II PR constant but not always followed by QRS), 3rd no association between P and QRS

Left bundle branch block (wiLLiam) - ‘w’ shape in V1 + ‘m’ shape in V6, broad QRS, prolonged / broad R wave in V5/6, dominant S wave in V1, absence of Q waves in lateral leads
Right bundle branch block (moRRow) - ‘m’ shape in V1 + ‘w’ shape in V6, broad QRS, slurred S waves in lateral leads

Question 25

How do you manage tachycardias

Answer 25

Tachycardia: beta blockers and calcium channel blockers. AV node reentry tachycardia most common - catheter ablation. If systolic < 90 - DC cardioversion Supraventricular T: adenosine, verapamil (can’t be given with BB) Broad complex: IV amiodarone, DC cardioversion (haemodynamically unstable)

Question 26

How is AF investigated

Answer 26

ECG: irregularly irregular, absent P waves, narrow QRS Echo to see if structural Bloods: FBC, U+Es, TFTs, LFTs, clotting profile Also CHADSVasc and ORBIT

Question 27

How is AF managed

Answer 27

Acute: haemodynamically unstable - electrically cardioverted, stable and <48h rate / rhythm, >48h rate control Rate or rhythm: rate control FL unless: AF reversible, new onset within 48h, HF caused by AF. Rate (ventricular): beta blocker (atenolol) or rate limiting CCB (verapamil, diltiazem) (avoid in HF), digoxin if unsuitable, dual therapy Rhythm (sinus): cardioversion + long term rhythm control, beta blocker FL, dronedarone SL (or amiodarone (LV impairment / HF), consider left atrial ablation Cardioversion is immediate if <48h or haemodynamically unstable; electrical (defib under sedation), pharmacological - flecainide, amiodarone Both ineffective or not tolerated: LA ablation, AV node ablation + pacemaker DOAC for clots, warfarin if DOAC contraindicated, both contraindicated - consider left atrial appendage occlusion

Question 28

Describe the different types of heart block

Answer 28

First degree (PR + QRS still associated): PR interval >0.2s. Usually asymptomatic and does not need to be treated, slower conduction time, age, myocarditis, hypothyroidism, medications Second degree (slightly associated): Mobitz I: progressively prolonged PR until beat dropped; Mobitz II: PR is constant but P wave often not followed by QRS Intermittent blockage of waves, usually a structural change: IHD, fibrosis, degeneration of AV node. MII has higher risk of progression to complete block Third: no association between P and QRS. Atria and ventricles beat independently (atria usually quicker), damage to AVn or bundle of His, MI, congenital

Question 29

What are the 3 presentations of peripheral arterial disease

Answer 29

Intermittent claudication: cramping in leg, due to exertion, relieves with rest Acute limb ischaemia (6 Ps): pain, pallor, pulseless, paralysis, paraesthesia, perishing cold Leriche syndrome: thigh / buttock claudication, absent femoral pulses, male impotence (occlusion of distal aorta / common iliac)

Question 30

What is Virchow's triad, what is the difference between arterial and venous clot formation, what are the risk factors for VTE

Answer 30

Virchow's triad for clot formation - stasis of blood flow (longer contact), endothelial injury (exposed collagen and stimulates), hypercoagulation Arterial platelet driven, inflammation/ trauma/ infection. Venous fibrin driven, stasis usually issue RF: immobility, recent surgery, cancer, long haul travel, pregnancy, oestrogen, polycythaemia, SLE, thrombophilias

Question 31

What are the signs and examination tests for PAD and DVT

Answer 31

Signs: skin pallor, cyanosis, dependent rubor, muscle wasting, hair loss, ulcers, poor wound healing, gangrene, reduce skin temp + sensation, prolonged CRT, changes in Buerger’s Buerger’s: lie supine with legs at 45 degrees, hold for 1-2m looking for pallor. Sit patient up with legs hanging; healthy will go pink, PAD will go blue then dark red (rubor) leg pain / tenderness, swelling (pitting oedema), dilated veins, warm, erythema, ulcers Measure calf circumference 10cm below tibial tuberosity, >3cm bigger than other - positive

Question 32

How is PAD investigated and treated

Answer 32

PAD: ankle-brachial index only necessary. Duplex US and angiography for flow and surgery Ratio of systolic in ankle vs arm 0.9-1.3 healthy, 0.6-0.9 mild, 0.3-0.6 moderate, <0.3 severe Non limiting claudication: aspirin / clopidogrel, exercise therapy, lifestyle changes; lifestyle limiting add: cilostazol (several cardiac contraindications) or naftidrofuryl, surgical revascularisation Acute limb ischaemia: emergency, endovascular or surgical revascularisation + thrombolysis / amputation, aspirin / clopidogrel + heparin, appropriate analgesia

Question 33

How is DVT investigated and treated

Answer 33

DVT: Well's score, D-dimer blood test (sensitive not specific), duplex ultrasound (CT/MRI venography), bloods (FBC, LFTs, U+Es, clotting profile) Well’s score: likely - US, unlikely - d-dimer DVT: apixaban / rivaroxaban FL (start as soon as suspected), enoxaparin / dalteparin SL (FL in pregnancy), exercise, compression stockings Long term anticoagulants for unprovoked, 3m for reversible cause, 3-6m cancer

Question 34

What are the causes of pericarditis

Answer 34

Majority are idiopathic and seen in young adults Range of pathogens (viruses, bacterial and some fungal) Noninfectious: Sjorgen’s, rheumatoid arthritis, SLE, secondary metastatic tumours, trauma, iatrogenic, MI, uraemia

Question 35

How does pericarditis affect the function of the heart

Answer 35

Effusion commonly occurs with pericarditis, if volume large enough ventricular filling is compromised (tamponade), reduces diastole and therefore systole - requires emergency drainage

Question 36

How does pericarditis present

Answer 36

Chest pain - severe, sharp + pleuritic (not crushing), rapid onset, worse lying flat (alleviated by sitting up), left anterior chest (radiates to arm/ trapezius ridge) Low grade fever and prodrome of myalgia Pericardial rub on auscultation (rubbing / scratching)

Question 37

How is pericarditis investigated

Answer 37

ECG - PR depression, global saddle shaped ST elevation, (STEMI would just be one infarcted area) X ray (maybe cardiomegaly), echocardiogram Bloods: troponin, FBC (slight increase in white count), high ESR indicative of autoimmune, U+Es (uraemia cause)

Question 38

How is pericarditis treated

Answer 38

Aspirin / ibuprofen high dose (+ PPI), colchicine (for 3m to stop recurrence), exercise restriction In more extreme cases oral corticosteroids or pericardiectomy might be appropriate Treat cause; if purulent: IV abx (tailored to blood cultures), steroids for autoimmune Tamponade - pericardiocentesis, also for purulent or neoplastic

Question 39

Describe constrictive pericarditis

Answer 39

Constrictive - becomes inelastic/ fibrous/ calcified and interferes with diastolic filling. Can occur in any types but common in TB and rheumatic heart disease Ascites, oedema, right heart failure, atrial dilation

Question 40

Describe the murmurs of valve pathologies

Answer 40

Mitral stenosis: mid diastolic, low pitched rumbling, loud S1, LUB dub durr (In diastole, slow velocity, stiff valves snap back with enough force. Palpable apex beat) Mitral regurgitation - pan systolic, high pitched, S3, radiates to axilla (Flowing wrong direction during systole, high velocity from ventricle, backlog of blood in LA causes S3) Aortic stenosis (most common): ejection systolic, high pitched, crescendo-decrescendo, slow rising pulse + narrow pulse pressure, burrr dub (High velocity through small gap, reduced cardiac output + systolic pressure, prolonged LV ejection) Aortic regurgitation: early diastolic soft murmur, collapsing pulse + wide pulse pressure, Lub tarrr (Small amount returning after systole, drop in aortic pressure during diastole as blood flows back. Aortic thrill) Tricuspid regurgitation (similar to mitral): pan systolic, high pitched, split S2, inspiration (Blood returns to RA during systole - faster velocity, RV empties quicker than LV, increased venous return on inspiration) Pulmonary stenosis: ejection systolic, harsh, crescendo-decrescendo, ejection click (High pressure through small hole during systole, click due to stenotic valve leaflets, heard best on inspiration, pulmonary thrill)

Question 41

How are valve pathologies investigated

Answer 41

Echocardiogram gold standard - size, function, valve structure Serial echos to monitor Heart sounds, ECG when hypertrophy Blood pressure - aortic regurgitation: high systolic, low diastolic

Question 42

Describe the pathophysiology of infective endocarditis

Answer 42

Infection of endothelium, most commonly the heart valves, bacteria in bloodstream adhere to damaged area, vegetations form (bacteria, platelets, fibrin) Most common cause: staph aureus; also streptococcus (viridans), enterococcus (faecalis) Risk factors: IV drug use, structural heart pathology, CKD (dialysis), immunocompromised, past Hx Structural: valvular / prosthetic disease, congenital, hypertrophic cardiomyopathy, pacemakers Complications: valve pathology, HF, infective / non infective emboli, glomerulonephritis + renal impairment

Question 43

How does infective endocarditis present

Answer 43

Presentation: fever, fatigue, night sweats, muscle aches, anorexia Signs: new / changing murmur, splinter haemorrhages, petechiae, janeway lesions, osler’s nodes, roth spots, splenomegaly, finger clubbing JL: red macules on palms + soles, ON: tender red nodules on pads of fingers + toes, RS: haemorrhages on retina

Question 44

How is infective endocarditis investigated, what criteria is used

Answer 44

Blood cultures essential, 3 samples 6h apart from different sites (unless septic). Transoesophageal echo, prosthetic valves - SPECT-CT Modified Duke criteria: major: persistent positive blood cultures, positive imaging; minor: predisposition, T > 38C, vascular phenomena, immunological phenomena, microbiological phenomena Diagnosis: 2 major, 1 major + 3 minor, 5 minor (V: splenic infarction, intracranial haemorrhage, Janeway; I: osler’s, roth spots, glomerulonephritis; M: positive cultures not qualifying as major)

Question 45

How is infective endocarditis managed

Answer 45

Managed by specialist team, IV broad spectrum Abx, 4w or 6w for prosthetic Surgery required for HF related to valve pathology, large vegetations / abscesses, not responding to Abx

Question 46

Describe the types of shock

Answer 46

Hypovolaemia, cardiogenic (not pumping), distributive (sepsis, anaphylaxis, neurogenic), obstructive Hypovolaemic - secondary to haemorrhagic shock, acute loss of blood, loss of fluid (burns, pancreatitis), extreme vomiting / diarrhoea Cardiogenic - tamponade, pulmonary embolism, acute MI, fluid overload, myocarditis Decreased cardiac contractility, decreased cardiac output and blood pressure Obstructive: physical obstruction of great vessels (tamponade, PE, tension pneumothorax) Distributive: neurogenic: loss of sympathetic tone in vessels (slow HR, less venous return, less CO); vasoactive: release of massive vasoactive mediators, massive vasodilation

Question 47

Describe the types of cardiomyopathies

Answer 47

Dilated (LV) most common, contracts poorly, like HF: dyspnoea, fatigue, p oedema, arrhythmias Genetic, infections (coxsackie B), alcohol abuse (toxic, B1 deficiency, inflammation, hypertension), pregnancy (peripartum CM), SLE, RA Hypertrophic obstructive: LV hypertrophy, deviated septum blocks outflow, autosomal dominant. Risk of HF, arrhythmias, sudden cardiac death. Non specific symptoms, severe present like HF Restrictive: stiffening of muscle - impaired systolic filling, HF symptoms Amyloidosis, sarcoidosis, infiltrative - haemochromatosis, radiation therapy Arrhythmogenic: muscle replaced with fibrofatty tissue - ventricular arrhythmias and sudden death Takotsubo: LV dysfunction following severe emotional stress, ‘Broken heart syndrome’, resolves

Question 48

What are the causes of the different types of anaemia

Answer 48

Micro (synthesis issue): iron deficiency, thalassaemia (globin chains), lead poisoning (haem) Normo: haemolytic (rhesus / ABO, sickle cell, malaria, transfusion reaction), chronic disease (TB, HIV, CKD, SLE), haemorrhage, cancer Macrocytic: B12 + folate (DNA), alcohol abuse (liver → B12 + folate), myelodysplastic syndromes

Question 49

Describe the pathophysiology of sickle cell

Answer 49

Sickle cell - mutation causes abnormal beta chain, insoluble and polymerised when deoxygenated (causes spiral effect with acute chest syndrome). RBCs are more rigid, repeated sickling becomes irreversible, carries oxygen less efficiently and blocks vessels. Acute chest syndrome: lung damage (sickling and infection) → hypoxia → HbS polymerisation → reduced flow → more lung damage

Question 50

How do you investigate anaemia

Answer 50

Blood count + film (micro/ normo/ macro) Reticulocyte count - measure of production (how many young cells) Serum iron/ ferritin. Direct antiglobulin test for autoimmune. LFT / Bilirubin (increased haemolysis). Sickle cell solubility + Hb separation

Question 51

How is sickle cell anaemia managed

Answer 51

Sickle cell - hydroxycarbamide (increases foetal haemoglobin), supportive (vaccines, prophylactic penicillin, analgesia), repeat transfusions, stem cell transplant Acute chest: oxygen, incentive spirometry, analgesia (depending on pain), broad spectrum abx

Question 52

Describe the different types of leukaemia (age, blood film, specificifiers)

Answer 52

Acute lymphoblastic: 2-4, blasts on blood film (children = B, adults = T) Acute myeloid: 60s, may have normal WCC, most deadly, auer rods Chronic myeloid: 60s, 80% have philadelphia chromosome, very high WCC, give imatinib (tyrosine kinase) Chronic lymphocytic: elderly, most common, lack of apoptosis, smudge cells, often no symptoms Order by age (acutes before chronic): lymphoblastic, myeloid, lymphocytic (also most to least aggressive) Specifiers: BAPS - blasts, auer roads, philadelphia chromosone, smudge cells

Question 53

How are leukaemias treated

Answer 53

Treatment: chemotherapy, radiation, stem transplant, targeted. Staging and overall health considered for treatment type. Chemo: methotrexate, vincristine, daunorubicin, cytarabine

Question 54

How are lymphomas classified

Answer 54

Classifications: Hodgkin (Reed-Sternberg cells - characteristic mirror image nuclei) vs Non-Hodgkin (low grade vs high grade, B vs T vs Nk, Burkitt, MALT). Non-H: 80% B cell (diffuse large B most common)

Question 55

What are the risk factors for lymphomas

Answer 55

Hodgkin's: Ages 20-25 or 80+, HIV, Epstein-Barr virus, autoimmune conditions, family history Non-Hodgkin's: HIV, EBV, H pylori (MALT), Hep B+C, exposure to pesticides / trichloroethylene, family history

Question 56

How does lymphoma present

Answer 56

Lymphadenopathy, fever, weight loss, night sweats Fatigue, itching, cough, SOB, abdo pain, recurrent infections

Question 57

What is the pathophysiology of multiple myeloma

Answer 57

Accumulation of malignant plasma cells leads to progressive bone marrow failure. They produce excess of one type of monoclonal immunoglobulin (M / paraproteins) Plasma cells stimulate osteoclasts and inhibit osteoblasts - osteoporosis (releases calcium into blood). Immunoglobulins deposit in kidneys and cause dysfunction - proteinuria Other immunoglobulin levels are decreased resulting in immunoparesis and susceptibility to infections Plasma viscosity increases due to increased proteins - haemorrhages (stroke, retinal etc)

Question 58

What is the presentation of multiple myeloma

Answer 58

old CRAB: average age is 70. Calcium elevated, Renal impairment, Anaemia, Bone disease Recurrent infections due to neutropenia Bone disease leads to osteolytic lesions, pathological fracture and spinal compression Unexplained fatigue / weight loss / fever, bone pain, abdo discomfort

Question 59

How is myeloma investigated

Answer 59

Bloods: calcium, FBC (anaemia), U+Es (raised creatinine + urea, reduced creatinine clearance), peripheral smear (Rouleaux - stacked RBCs), plasma viscosity / ESR in primary care Bone marrow biopsy most important, clonal plasma cells >10% Immunoglobulins: serum quantitative immunoglobulins, serum/urine protein electrophoresis + immunofixation (urine = Bence-Jones proteins), light chain assay Whole body MRI / CT - osteolytic lesions, ‘rain drop’ skull

Question 60

What is the pathophysiology of primary and secondary polycycthaemia

Answer 60

Primary - polycythaemia vera blood cancer (malignant proliferation of a stem cell leading to excess proliferation of RBCs, white and platelets) Secondary - hypoxia (altitude, chronic lung disease), inappropriate high erythropoietin secretion (kidney/ liver cancer), congenital heart disease

Question 61

What are the 3 myeloproliferative disorders and what cells are in excess

Answer 61

Polycythaemia vera - RBCs (also white cells and platelets) Primary myelofibrosis - dysplastic megakaryocytes (also immature white cells and teapdrop RBCs, pantocytopenia in advanced) Essential thrombocythaemia - platelets (also increased megakaryocytes)

Question 62

What gene is linked to myeloproliferative disorders and what treatments are used

Answer 62

Hydroxycarbamide is the chemo of choice, aspirin / clopidogrel and venesection for polycythaemia, JAK2 inhibitor ruxoltinib for primary myelofibrosis

Question 63

What is the pathophysiology of Von Willebrand's

Answer 63

Most types dominant, vW factor - promotes platelet adhesion to damaged endothelium and stabilises VIII. Deficiency causes bleeding; majority type 1 (less severe) partial reduction, type 2 abnormal vW, type 3 complete lack (recessive)

Question 64

How is von Willebrand diagnosed and managed

Answer 64

Prolonged PT and aPTT, vW factor antigen Desmopressin stimulates release of vWF, tranexamic acid, factor infusions (+ VIII)

Question 65

What is the pathophsyiology of haemophilia A and B

Answer 65

X-linked recessive (females can be carriers, all males); A - deficiency in factor VIII, B - factor IX

Question 66

How is haemophilia diagnosed and managed

Answer 66

Prolonged activated partial thromboplastin time (aPTT), factor VIII and IX assay Give factor concentrates and tranexamic acid (antifibrinolytic)

Question 67

What is the pathophysiology of antiphospholipid syndrome

Answer 67

AI - antibodies bind to phospholipid-binding proteins (i.e. prothrombin), causing damage and activation and venous / arterial thrombosis (causes endothelial damage and platelet activation). Can occur in isolation or part of another condition - most commonly SLE

Question 68

How is antiphospholipid syndrome diagnosed and managed

Answer 68

Diagnosis from antibodies: lupus anticoagulant, anticardiolipin, anti-beta2 glycoprotein I Also thrombocytopenia and prolonged aPTT Primary thromboprophylaxis - aspirin and enoxaparin (or long term warfarin (INR 2-3)) In pregnancy can cause recurrent miscarriage, pre-eclampsia, placental abruption, pre term, VTE LMWH until 34w