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Section 1 Fluid and Haemodynamics (no answers) 1) Systemic thromboemboli: a) b) c) d) e) 60% arise from intracardiac thrombi 25% are of unknown origin 75% of arteriolar embolisation are in the lower limbs 20% of arteriolar embolisation are in the brain paradoxical emboli may enter pulmonary circulation 2) Stroke cascade in sepsis is: a) b) c) d) e) LPS TNF LPS LPS ILI TNF LPS ILI TNF LPS IL6/8 ILI IL6/8 ILI TNF ILI IL6/8 TNF IL6/8 IL6/8 3) All the following are important leucocyte adhesion molecules EXCEPT: a) b) c) d) e) ICAM I VCAM I LTB 4 P-selectin E-selectin 4) In acute inflammation: a) b) c) d) e) mean capillary pressure is reduced by arteriolar dilation and opening of capillary beds there is accumulation of extravascular fluid with specific gravity > 0.012 neutrophils usually predominate for the first 48 hours phagocytosis may cause tissue damage in viral infections, monocytes are the first cells to arrive Section 2 Haemostasis, Thrombosis & Haemorrhage 1) Regarding tissue factor/tissue thromboplastin: a) b) c) d) e) 2) With regard to haemostasis, all of the following are true EXCEPT: a) b) c) d) e) 3) brain lower limbs coronary vessels renal vessels spleen Which is not an anti-coagulant? a) b) c) d) e) 5) von Willebrands factor acts as a molecular bridge between platelets and collagen platelets bind von Willebrands factor via a glycoprotein receptor Go IIb/IIIa complex activated platelets bind to each other using fibrinogen as bridge molecules platelet adhesion results in release reaction and exposes surface binding sites activated platelets accelerate activation of prothrombin 20,000 fold Major sites of lodgement of systemic emboli include all of the following EXCEPT: a) b) c) d) e) 4) its production by endothelial cells can be induced by IL-1 and TNF its production by endothelial cells can be induced by bacterial exotoxin it activates the extrinsic clotting system it activates factor VII all of the above are true thrombomodulin protein C protein S anti-thrombin IH thromboplastin Which of the following is contained in the cytoplasmic granules of platelets? a) b) c) d) e) ADP thrombin von Willebrands factor P-selectin glycoprotein receptor Gp 16 6) Functional deficiencies of all of the following prolong INR EXCEPT: a) b) c) d) e) 7) Regarding protein C, all of the following are true EXCEPT: a) b) c) d) e) 8) it inactivates factors Va and VIIIa it is a vitamin K dependent on plasma protein it uses protein S as a co-factor it is activated by the thrombomodulin-thrombin complex it stimulates conversion of plasminogen to plasmin All of these factor sites of origin pairs are true EXCEPT: a) b) c) d) e) 9) fibrinogen factor V factor VII factor X factor IX thromboxane is formed by activated platelets protein S is synthesised by endothelial cells prostacyclin is elaborated by platelets endothelial cells synthesise and secrete von Willebrands factor fibrin stabilising factor is released from platelets The activation of protein C: a) b) c) d) e) is inhibited by endothelial cells may cause intrinsic coagulation pathway inhibition increases the activity of anti-thrombin M is not affected by warfarin administration stimulates the platelet secretion-release reaction 10) All of the following is released by activated platelets EXCEPT: a) b) c) d) e) ADP prostacyclin factor Va serotonin ionised calcium 11) Prostacyclin (PGI2): a) b) c) d) e) is formed by the action of lipo-oxygenase on arachidonic acid is liberated by activated platelets is liberated by vascular endothelial cells enhances platelet aggregation enhances thrombomodulin activity 12) Regarding the clotting pathways, all of the following are true EXCEPT: a) b) c) d) e) a prolonged APT indicates a defect in the intrinsic pathway the intrinsic pathway is more important in vivo than the extrinsic pathway the extrinsic pathway is initiated by tissue factor acting on factor VII factor X is common to both pathways deficiency of factor XII does NOT cause a bleeding tendency 13) Regarding platelets, all of the following are true EXCEPT: a) they do not have nuclei and cannot reproduce b) they contain actin, myosin and tropomyosin in the cytoplasm, which are all contractile proteins c) they are coated with glycoproteins that cause them to avoid adherence to normal endothelium d) contain alpha granules which are rich in ADP and Ca++ e) form thromboxane helping platelet aggregation 14) Factor VIIa: a) b) c) d) e) is a component of the extrinsic clotting pathway directly activates factor IX is inhibited by protein C its deficiency results in von Willebrands disease is dependent on vitamin K for its synthesis 15) The mechanisms of thrombin involvement in thrombosis include all the following EXCEPT: a) b) c) d) e) increased P-selectin presentation on endothelial surfaces conversion of prothrombin to thrombin factor V and VII activation decreased mast cell heparin release increased platelet aggregation 16) With regard to haemostasis, all of the following are correct EXCEPT: a) b) c) d) e) activated protein C degrades factors Va and VIIIa protein C is activated by thrombin in the presence of thrombomodulin factor VIII is activated by thrombin the primary haemostatic plug is formed by platelet aggregation due to thrombin protein S is a co-factor for protein C 17) Stasis of blood flow results in thrombosis because: a) b) c) d) disruption of fresh blood flow results in less dilution of activated clotting factors disruption of fresh blood flow results in reduced inflow of inhibitors of clotting factor it results in decreased local release of prostacyclin (PG12) and tPA all of the above 18) In acute hypovolaemic shock, angiotensin: a) b) c) d) e) stimulates the central nervous system’s ischaemic response is responsible for the reverse stress-relaxation response of the circulatory system is not a significant factor in acute compensation inhibits the release of vasopressin contributes towards compensation after baroreceptor responses have been evoked 19) With regard to the in-vitro clotting of blood samples, all of the following are true EXCEPT: a) b) c) d) e) blood usually clots when placed in a glass tube within 4-8 minutes clotting can be prevented by adding EDTA which chelates calcium recalcified plasma usually clots in 2-4 minutes the APPT is performed by adding thromboplastin to recalcified plasma the normal APPT is 26-33 seconds 20) Vitamin K is required for the activation of: a) b) c) d) e) pre-kallikrein Hageman factor von Willebrands factor protein C plasminogen 21) Thrombus formation is inhibited by: a) b) c) d) e) von Willebrands factor IL-1 alpha 2 – macroglobulin TNF endothelial cell injury 22) Most pulmonary emboli: a) b) c) d) e) cause centrally located pulmonary haemorrhage cause pulmonary infarction cause acute right heart failure are clinically silent lead to pulmonary hypertension 23) In normal haemostasis: a) b) c) d) e) factor V inhibits thrombosis alpha 2 macroglobulin is antithrombotic PGI2 favours platelet aggregation platelet aggregation is inhibited by von Willebrands factor tissue plasminogen activator is responsible for prothrombotic events 24) Normal endothelial cells decrease platelet aggregation by secreting: a) b) c) d) e) Interleukin-1 von Willebrands factor prostacyclin factor V thromboplastin 25) Thrombosis is potentiated by all of the following EXCEPT: a) b) c) d) e) von Willebrands factor deficiency protein S deficiency antithrombin III deficiency thrombotic thrombocytopaenia acute leukaemia 26) Acute compensatory mechanisms in shock include all the following EXCEPT: a) b) c) d) e) baroreceptor reflexes reverse stress – relaxation of vascular smooth muscle the effects of increased aldosterone secretion activation of the renin-angiotensin system the central nervous system ischaemic response 27) Prothrombotic characteristics of endothelium include: a) b) c) d) e) plasminogen activator prostacyclin von Willebrands factor thrombomodulin heparin like molecules Section 2 Haemostasis, Thrombosis and Haemorrhage - Answers 1) 2) 3) 4) 5) 6) 7) 8) 9) 10) 11) 12) 13) 14) 15) 16) 17) 18) 19) 20) 21) 22) 23) 24) 25) 26) 27) E B C E A E E C B B C B D C D D E E D D C D B C A C C Section 3 Haemorrhage and Shock 1) The classic stages of shock include all of the following EXCEPT: a) compensated stage which begins with mild hypotension, tachycardia, pallor and cold extremities including septic shock b) decompensating stage which include decline in blood pressure and rapid pulse c) irreversible shock where all therapeutic efforts are to no avail d) full recovery is possible, however there is a much higher mortality with patients with cardiogenic shock e) all of the above are stages of shock 2) Which statement regarding shock is INCORRECT? a) b) c) d) e) cardiogenic shock has a higher mortality than neurogenic shock “progressive” / “demonstrated” shock is usually irreversible nephrotic syndrome is associated with loss of fluid from all fluid compartments oliguria usually precedes diuresis angiotensin and vasopressin levels increase within one hour 3) Shock: a) is caused by a loss of 25% of the blood volume in a healthy individual b) is caused primarily by cardiac failure and has a 40% mortality with modern treatment c) is caused by sudden haemorrhage and will stimulate a maximal response from the reninangiotensin system within 10 minutes d) is caused by endotoxins and is mediated largely by the release of ILY and TNF from macrophages e) will cause the “central nervous system ischaemic response” when the systolic blood pressure is less than 80mmHg 4) The most potent vasopastic substance is: a) b) c) d) e) histamine leukotriene C4 platelet activating factor TNF-α serotonin 5) Mediators of septic shock include all of the following EXCEPT: a) b) c) d) e) IL-6 C5a PAF catecholamines TNF antibodies Section 3 Haemorrhage and Shock – Answers 1) 2) 3) 4) 5) A B D B E Section 4 Haemodynamic disorders, thrombosis and shock 1) Hypercoagulability: a) is most commonly caused by the factor V Leiden mutation, present in 1-2% of the white population b) may be caused by an inherited excess of protein C or protein S c) can result from a congenitally reduced level of homocysteine d) is the most frequent cause of thrombotic disease e) may be caused by heparin-induced thrombocytopaenia 2) Regarding thrombi, which one of the following statements is NOT true? a) arterial thrombi usually begin at the site of endothelial damage or turbulence, whereas venous thrombi start in areas of stasis b) arterial thrombi tend to propagate in a retrograde direction to the point of attachment whereas venous thrombi tend to extend in the direction of blood flow c) 30% of DVTs in the larger leg veins are asymptomatic and clinically undetectable d) venous thrombosis commonly affects the veins of the lower extremities, with only 10% occurring in other sites e) activation of the fibrinolytic pathway can lead to total lysis and complete resolution of recent thrombi 3) Regarding pulmonary emboli: a) most are clinically detectable by a tachypnoea, dyspnoea and tachycardia b) sudden death and/or cardiovascular collapse occur when over 40% of the pulmonary circulation is obstructed by emboli c) embolic obstruction of medium sized pulmonary vessels results in pulmonary infarction and loss of respiratory capacity d) fewer than 5% of pulmonary emboli originate outside the deep veins of the legs e) multiple pulmonary emboli are unlikely to have a clinical effect if they occur over a prolonged period of time Section 4 Haemodynamic disorders, thrombosis and shock – Answers 1) 2) 3) E C D Section 5 Haematopoietic System 1) Hereditary spherocytosis: a) b) c) d) e) is asymptomatic in 50% of cases frequently presents at birth with marked jaundice causes cholelithiasis in up to 50% of affected adults causes massive splenic enlargement is cured by splenectomy 2) Glucose G phosphate dehydrogenase deficiency: a) b) c) d) e) is X-linked is believed to protect against malaria (plasmodium fal????) can cause intravascular and extravascular haemolysis rarely display the morphologic changes of chronic haemolytic anaemia all above are true 3) Sickle cell disease: a) b) c) d) e) sufferers are heterozygous frequently presents in the neonatal period usually causes splenomegaly in adults involves abnormal alpha-globin causes “crew haircut” appearance on skull x-rays 4) Sickling may be precipitated by: a) b) c) d) e) HbA dehydration increased pH HbF co-existent alpha-thalanaemia 5) The commonest cause of death in children with sickle cell anaemia is: a) b) c) d) e) severe anaemia infection by unencapsulated bacteria vaso-occlusive complications osteomyelitis heart failure 6) Αlpha-thalanaemia: a) b) c) d) e) is more common than beta-thalanaemia is more severe than beta-thalanaemia can cause intrauterine death (hydrops foetalis) is rarely asymptomatic usually requires regular transfusions 7) Beta-thalanaemia: a) b) c) d) e) involves excess beta-globin production causes spherocytes in peripheral blood ????? results in ineffective erythropoiesis is manifest at birth in severe cases is a cause of primary haemochromatosis 8) Paroxysmal nocturnal haemoglobinuria: a) b) c) d) e) is a congenital hereditary condition affects white cell, platelet and red cell function is rarely fatal is not associated with aplastic anaemia causes paroxysmal and nocturnal intravascular haemolysis in more than 75% cases 9) Immune haemolytic anaemia of warm antibody type includes: a) b) c) d) e) systemic lupus erythematosus syphilis mycoplasma pneumoniae measles mumps 10) Causes of folic acid deficiency include: a) b) c) d) e) ileac resection anticonvulsant pernicious anaemia vegetarianism ????? infection with fish tapeworm Section 5 Haematopoietic System – Answers 1) 2) 3) 4) 5) 6) 7) 8) 9) 10) C E E B B C C B A B Section 6 Leucopoenia, Leukocytosis, spleen, blood group 1) The normal spleen: a) b) c) d) e) stores >50% body platelets stores 30-40ml of red blood cells is frequently the site of primary disease is an important primary organ of the immune system has a periarteriolar sheath of β lymphocytes 2) Splenomegaly in adults can be caused by all EXCEPT: a) b) c) d) e) amyloidosis Epstein-Barr virus multiple myeloma rheumatoid arthritis sickle cell anaemia 3) Patients with polycythaemia veins: a) b) c) d) e) frequently have splenomegaly in the early stages usually have a haematocrit of ≥ 60% are all hypertensive have normal levels of erythropoietin (serum) usually present with thrombotic episodes 4) The most common site of multiple myeloma lesions is: a) b) c) d) e) vertebral column skull pelvis femur clavicle 5) Severe infections tend to occur when the neutrophil count drops below: a) b) c) d) e) 100 cells/mm3 blood 500 cells/mm3 blood 1000 cells/mm3 blood 1500 cells/mm3 blood 3000 cells/mm3 blood 6) Basophilic leukocytosis is seen in: a) b) c) d) e) severe burns periphagus inflammatory bowel disease myeloproliferative disease non Hodgkin lymphomas 7) The life-span of a neutrophil in the circulation is: a) b) c) d) e) 6-7 hours 12-24 hours 24-45 hours 4-5 days none of the above 8) Blood transfusion reaction is an example of a: a) b) c) d) e) type I hypersensitivity reaction type II hypersensitivity reaction type III hypersensitivity reaction type IV hypersensitivity reaction (rather embarrassing monumental cock-up) 9) Regarding rhesus blood groups: a) b) c) d) e) rhesus antibodies are innate there are three types of rhesus factors rhesus ‘D’ is the mast prevalent and antigenic rhesasta most Caucasians are “rhesus negative” maximal antibody response occurs 2-4 weeks after initial exposure 10) Type O blood: a) b) c) d) e) can be safely transfused into anyone contains anti A and anti B antigens at birth red cells have O, A and B antigens on their surface is the commonest blood type in Caucasians show maximal anti-A and anti-B titres in 20-30 year old Section 6 Leucopoenia, leukocytosis, spleen, blood groups – Answers 1) 2) 3) 4) 5) 6) 7) 8) 9) 10) 11) B E B A B D A B C D D Section 7 1) In acute infection which cytokine is responsible for the leukocytosis? a) b) c) d) e) IL-1 IL-2 IL-4 IL-5 IFN-X 2) Which of the following conditions would a barophitic leukocytosis be most likely in? a) b) c) d) e) bacterial infection asthma myeloproliferative conditions parasitic infection myelodysplastic conditions 3) Neutropenia associated with ineffective granulopoiesis include: a) b) c) d) e) hypersplenism aplastic anaemia alkylating agents (CXT) SLE vitamin B12 deficiency 4) Lead poisoning leads to a: a) b) c) d) e) megaloblastic anaemia haemolytic anaemia microcytic anaemia hypodromic anaemia aplastic anaemia 5) Acute cold agglutinin haemolytic anaemia is seen in: a) b) c) d) e) SLE lymphoma leukaemia mycoplasma infection paroxysmal cold haemoglobinuria Section 7 Answers 1) 2) 3) 4) 5) A C E B D Section 8 Haematology 1) Monocytosis is seen in: a) b) c) d) e) burns non-Hodgkin lymphoma chronic myelogenous leukaemia inflammatory bowel diseases hay fever 2) Mycoplasmal infections can cause: a) b) c) d) e) megaloblastic anaemia aplastic anaemia warm antibody haemolytic anaemia cold agglutinin immune haemolytic anaemia cold haemolysis haemolytic anaemia 3) Sickle cell disease: a) b) c) d) e) is seen in heterozygotes for Hbs if severe, is present at birth splenomegaly is a late sign painful bone crises are extremely common in children is a type of intravascular haemolytic anaemia 4) Folic acid deficiency is seen in: a) b) c) d) e) vegetarianism gastrectomy disseminated cancer fish tapeworm infection ileitis 5) Regarding pernicious anaemia: a) b) c) d) e) it is an important cause of folic acid deficiency intrinsic factor is secreted by chief cells in stomach it is usually diagnosed in adolescence intrinsic factor complexes with vitamin B12 in the stomach it is associated with myelin degeneration of dorsal and lateral tract Section 8 Haematology – Answers 1) 2) 3) 4) 5) D D D C E Section 9 Endocrine 1) Which is the most common pituitary adenoma? a) b) c) d) e) non-functioning adenoma growth hormone adenoma prolactin cell adenoma ACTH cell adenoma mixed growth hormone – prolactin adenoma 2) Regarding Hashimoto thyroiditis: a) b) c) d) e) women are five times more frequently affected than men some cases are HLA-B8 associated caused primarily by a B cell defect antibodies are directed against the iodine transporter presents as a symmetric, diffuse, painful enlargement of the thyroid, usually with hypothyroidism 3) Which feature is most frequently seen in Cushing syndrome? a) b) c) d) e) osteoporosis moon faces weakness and fatigability hypertension central obesity 4) Which is NOT an example of secondary hyperaldosteronism? a) b) c) d) e) congestive heart failure Conn syndrome renal artery stenosis hypoalbuminaemia pregnancy 5) Which is the most common cause of Addison’s disease? a) b) c) d) e) autoimmune adrenalitis tuberculosis metastatic cancer acute haemorrhagic necrosis drug-induced – of ACTH Section 9 Endocrine – Answers 1) 2) 3) 4) 5) C D E B A Section 10 Haematopoietic System 1) Regarding pernicious anaemia: a) b) c) d) e) it is more common among Mediterranean and Chinese people atrophic gastritis with failure of IF production is characteristic tapeworm infestation may sometimes be a cause becomes more rare in advancing age groups failure of terminal ileal receptor sites for IF is a common cause 2) Regarding B12 deficiency: a) b) c) d) e) dietary deficiency may deplete normal reserves after several weeks failure of B12 protein R splitting in elderly people may be a cause pepsin is not normally involved in the process of B12 absorption without IF, there can be no B12 absorption at all anaemia and spinal degeneration can be reversed with folate Section 10 Haematopoietic System - Answers 1) 2) B B Section 11 1) Which primary tumour is not responsible for ectopic ACTH production? a) b) c) d) islet cell tumours of the pancreas carcinoid tumours ductal cancer in the site of the breast small cell cancer of the lung 2) With respect to adrenocortical insufficiency, which is TRUE? a) b) c) d) e) Addison’s disease is commonly caused by infiltrative disease such as ????ser hyperpigmentation is not seen in this condition Na+ and K+ losses result in hypokalaemia and hyponatraemia resolution is normal with adequate cortisol replacement acute Waterhouse–Fridericksen syndrome responds well to appropriate steroid replacement 3) In the anterior pituitary, which is TRUE? a) somatotrophs make up the major cell component b) thyrotrophs produce TSH and lipotropin c) stimulation is via axons from the ??? supraoptic and paroventricular nuclei in the hypothalamus d) tumours of the pituitary are normally recognised by the mass effects with the cranium 4) Hypothyroidism, which is TRUE? a) b) c) d) is uncommonly caused by autoimmune destruction of the thyroid may result in elevated TSH levels detectable by blood test can cause gynaecomastia and amenorrhoea commonest cause in region with adequate iodine is drug induced 5) Parathyroid hormone: a) is secreted by the action PTH release protein b) commonest cause of secretion is primary hyperplasia c) over activity causes bone, kidney, gastrointestinal and central nervous system symptoms d) parathyroid levels are low in primary hyperparathyroidism 6) The commonest cause of hypothyroidism in iodine sufficient areas of the world is: a) b) c) d) e) Hashimoto thyroiditis developmental lack of thyroid parenchyma developmental deficiency of enzymes of thyroid hormone syndrome due to antithyroid medications radiation damage to thyroid gland 7) Regarding pituitary, which is TRUE? a) b) c) d) e) 50% of the pituitary gland is adenohypophysis posterior pituitary derives from Ratrike’s pouch corticotrophs and thyrotrophs are acidophilic cells the commonest type of pituitary adenoma is prolactin secreting adenomas non-functional adenoma are usually microadenomas 8) Regarding prolactin, which is TRUE? a) b) c) d) level decreases in hypothyroidism and renal failure level decreases by use of reserpine level decreases by neuroleptics non prolactin secreting adenomas can increase the pituitary prolactin secretion by stalk effect e) prolactin levels decrease by use of oestrogens 9) Which is false regarding null cell adenomas? a) b) c) d) e) null cell adenomas contribute to 20% of pituitary adenomas they do not produce hormones they can cause pituitary apoplexy they contain large numbers of secreting granules they cause hypothyroidism by destruction of normal pituitary cells Section 11 Answers 1) 2) 3) 4) 5) 6) 7) 8) 9) C D A B C A D D D Section 12 Haemostasis, Thrombosis and Embolism 1) Concerning thromboembolism: a) b) c) d) e) the majority of pulmonary emboli arise from deep calf vein and popliteal thrombosis about 40% of pulmonary emboli are clinically silent pulmonary hypertension is a common sequelae in pulmonary embolism cardiomyopathy is the commonest cause of systemic emboli the risk of renal infarction from thromboembolus is approximately equivalent to the risk of cerebral infarction 2) Concerning thrombi: a) b) c) d) arterial thrombi propagate in a retrograde direction (against flow) increased levels of protein C and S are risk factors for thrombi “lines of Zahn” are more prominent in venous than arterial thrombi deep venous thrombosis occurs in the following order of frequency: deep calf, popliteal, femoral, iliac e) femoral artery thrombi are rarely occlusive 3) Which of the following deficiency syndromes will predispose a patient to a bleeding disorder? a) b) c) d) e) protein C deficiency protein S deficiency factor XII (Hageman factor) deficiency vitamin C deficiency PGI2 deficiency 4) Of all hospitalised deaths, what percentage are wholly or largely due to pulmonary embolus? a) b) c) d) e) 5% 10% 20% 50% 75% 5) Which statement regarding tests in bleeding diseases is INCORRECT? a) b) c) d) e) clotting time is prolonged in thrombocytopaenia partial thromboplastin time detects changes in the intrinsic pathway Hess’ test is a measure of capillary fragility prothrombin time detects changes in the extrinsic pathway bleeding time is affected by the degree of hyperanaemia of the skin 6) Regarding thrombus formation, which of the following is INCORRECT? a) b) c) d) e) platelets aggregate when there is a decrease in intraplatelet levels of cyclic AMP primary haemostatic plug is formed due to the release of ADP platelet adhesion requires von Willebrands factor protein C deficiency increases the tendency to thrombus formation fibrin predominates in a pale thrombus 7) Which clotting factor is NOT synthesised by the liver? a) b) c) d) e) IX VII IV II V 8) Regarding disseminated intravascular coagulation, which of the following statements is INCORRECT? a) b) c) d) e) it involves the development of numerous microthrombi it is often a primary disorder it involves active fibrinolysis it is associated with increased FDPs it involves consumption of platelets and clotting factors 9) Which of the following is NOT found in alpha-granules of platelets? a) b) c) d) e) fibrinogen platelet derived growth factor ADP platelet factor IV fibronectin 10) Regarding the clotting cascade, which of the following is INCORRECT? a) formation of “prothrombin activator” is the rate limiting factor b) intrinsic pathway is more rapid than extrinsic pathway c) enough thrombin can be generated by clotting of 1ml of blood to coagulate all the fibrinogen in 3000mls of blood d) proteins C and S are reaction accelerators e) C’1 inactivator neutralises some activated clotting factors 11) Which statement regarding embolism is INCORRECT? a) b) c) d) e) amniotic fluid embolism has about 85% mortality gas embolism may lead to ischaemic necrosis of bone about 99% of emboli are thrombotic in origin most systemic thrombotic arise from valvular lesions free fatty acids induce toxic injury to micro-vessels in fat embolism syndrome 12) Regarding anti-thrombin III, which statement is INCORRECT? a) b) c) d) e) it combines with the inactivates most serine proteases anti-thrombin III deficiency usually presents in late adolescence or early adult life its action is enhanced by both exogenous and endogenous heparin it blocks the action of IIa on I it is a beta globulin 13) Which statement regarding platelets is INCORRECT? a) b) c) d) e) PGI2 promotes platelet aggregation they have a life span of about 10 days degranulation leads to activation of platelet factor III they cannot synthesise cyclo-oxygenase they carry class 1 MHC antigens 14) Which clotting factor is NOT vitamin K dependent? a) b) c) d) e) II IX X V VII 15) Which of the following is NOT found in dense bodies of platelets? a) b) c) d) e) factor IV histamine adrenaline beta-thromboglobulin serotonin 16) The control mechanisms of coagulation (anticoagulant) include all of the following EXCEPT: a) b) c) d) e) the depletion of clotting factors the clearance of activated factors stasis and turbulence of blood flow the inhibition of activated proteases fibrinolysis 17) Anti-thrombotic factors include all of the following EXCEPT: a) b) c) d) e) thrombomodulin protein C anti-thrombin III von Willebrands factor tissue plasminogen activator 18) Which of the following is the most important natural constraint to coagulation? a) b) c) d) e) protein C anti-thrombin III protein S endogenous heparin endogenous tPA 19) Regarding the fibrinolytic system, which of the following is INCORRECT? a) b) c) d) e) urokinase-like plasminogen activators (uPA) activate plasminogen in the fluid phase alpha-one-antitrypsin inhibits action of plasmin interleukin-1 inhibits synthesis of tPA-inhibitors tissue-type plasminogen activators (tPA) are mainly synthesised in endothelial cells small amounts of plasmin are formed in the blood all the time 20) Which of the following is NOT a platelet agonist (ie, does NOT induce platelet aggregation)? a) b) c) d) e) ADP nitric oxide thrombin adrenaline thromboxane A2 21) Thrombosis is potentiated by all of the following EXCEPT: a) b) c) d) e) von Willebrands factor deficiency protein S deficiency antithrombin III deficiency thrombotic thrombocytopaenia acute leukaemia 22) Prothrombotic characteristics of endothelium include? a) b) c) d) e) plasminogen activator prostacyclin von Willebrands factor thrombomodulin heparin-like molecules 23) Hageman factor activates the: a) b) c) d) e) complement system kinin system fibrinolytic system coagulation system all of the above Section 12 Haemostasis, Thrombosis and Embolism - Answers 1) 2) 3) 4) 5) 6) 7) 8) 9) 10) 11) 12) 13) 14) 15) 16) 17) 18) 19) 20) 21) 22) 23) E A E B A E C B C B D E A D D C D B C B A C E Viva Answer BLOOD GROUPS There are more than 30 groups of commonly occurring antigens on RBC, The two groups of greatest clinical significance are: 1 ABO 2 Rhesus ABO Possible blood groups; O, A, B, AB Inherited antigens on RBC surface: Gp O no surface antigens Gp A A surface antigens Gp B B surface antigens Gp AB A and B surface antigens (O,O) (AA or AO) (BB or BO) (AB) Do not possess antibodies at birth – but exposed AB antigens in food, or bacteria etc and develop antibodies spontaneously in early life Gp O → A and B antibodies Gp A → B antibodies Gp B → A antibodies Gp AB → no antibodies Anti A antibody levels are two times higher than anti B levels. Antibody levels decline with time (peak at 10 years) ABO Transfusion Reaction Antigen transfused RBC Antibody serum recipient Type II hypersensitivity rx???? Red cell clumping. Small red cell plugs in circulation Complement activation → lysis of RBC Opsonisation → phagocytosis (neutrophils and macrophages) Rhesus Six Rh factors; C, D, E, c, d, e Inherit one of each type of factor; C or c and D or d and E or e D is widely prevalent and most antigenic Anaemia Definition: Reduction in circulating red cell mass below normal limits for individual’s age and gender Classification Acute versus chronic Mechanism: Blood loss (acute/chronic) hereditary intrinsic Increased RBC destruction acquired extrinsic stem cell abnormality Impaired RBC production maturation abnormality By RBC appearance RBC size : micro / normo / macrocytic RBC pigmentation : hypo/normochrome Classification by mechanism 1 Blood loss; acute : chronic: 2 Increased RBC destruction; Haemolytic anaemias Intrinsic: hereditary: RBC membrane disorder, eg Hereditary spherolytosis RBC enzyme deficiency, eg GGPD Disorder RBC synthesis, eg deficient globulin thalassaemia eg abnormal globin sickle cell acquired: 3 trauma, haemorrhage GIT bleeding, menorrhazia RBC membrane defect, eg paroxysmal nocturnal haemoglobinuria Impaired RBC production Stem cell disturbance : aplastic anaemia, anaemia of CRF, Problem with RBC maturation : defective DNA synthesis: ↓B12, folate defective Hb synthesis : ↓iron TOPIC Haematology Haematology QUESTION ESSENTIAL KNOWLEDGE Discuss Rhesus blood Rhesus antigens are antigens occurring on RBCs that are group and its importance known to induce clinically significant immunologic disease via type II hypersensitivity /X. The other common group of antigens being the ABO group. 6 factors - C, D, E, c, d, e (inherent of each). - antigen D (Rh+) is widely prevalent and most antigenic - exposure of Rh- mother to Rh+ blood from foetus → development of antibodies over 2-4 weeks Classify the haemolytic Anaemia is decreased oxygen transport capacity of blood anaemias secondary to deficiency in RBCs. Males - Hb < 135gm/ml, Females – Hb < 120gm/ml Haemolytic anaemia is increased rate of destruction of RBCs, characterised by 1 shortened life span of RBCs 2 accumulation of products of HB catabolism 3 marked increased erythropoiesis Classification (various methods) 1 Extravascular haemolysis (spleen) 2 Intravascular haemolysis Extravascular haemolysis - injured or less deformable RBCs - hereditary sphenocytosis - sickle cell anaemia - G6PD deficiency Intravascular haemolysis - normal RBCs damaged by mechanical injury (eg mechanical heart valves, thrombi in microcirculation) - complement fixation (transfusion of mismatched blood) - exogenous toxic factors (falcipam and clostridin) - immune haemolytic anaemias 1 warm antibody type (lymphoma, leukaemia, dwas, SLE) 2 cold agglutinin type (mycoplasma, EBV, lymphoma) 3 cold haemolysis (paroxysmal cold haemoglobinuria) NOTES Subsequent exposure (eg snd pregnancy) causes serious type II hypersensitivity /X → erythroblastosis foetalis (jaundice, anaemia and hepatosplenomegaly)