Q21

Describe the pathophysiology of “disseminated intravascular coagulation”?

  • 2 major mechanisms trigger DIC:
    • Release of tissue factor into circulation
    • Widespread injury to the endothelial cells
  • Acute, subacute or chronic thrombo-haemorrhagic disorder characterized by
    • Excessive activation of coagulation leading to
    • Formation of thrombi in the microvascular circulation
    • Secondary activation of fibrinolysis causing bleeding
    • Consumption of platelets, fibrin and coagulation factors

Pass criteria:

  • 1 trigger and 2 out of 3 bolds

What are some of the important causes and triggers of severe DIC?

  • Obstetric complications (eg amniotic fluid embolism, FDIU) responsible for approximagtely 50% cases
  • Malignant neoplasms (33% cases)
  • Sepsis
  • Major trauma, severe burns, extensive surgery
  • Transfusion reaction
  • Most mild cases probably due to sepsis, esp in elderly, but not usually diagnosed – low platelets

Pass criteria:

  • 3 out of 6

Q22

Describe the pathogenesis of an aortic dissection.

  • Medial weakness (commonly from hypertension), medial hypertrophy vasa vasorum, intimal tear, blood flow dissects the media -> medial haematoma.
  • Cystic medial degeneration
  • Risk factors – HT, CT disease eg Marfan’s, Ehlers-Danlos, iatrogenic, pregnancy

Pass criteria:

  • Bold to pass

How are aortic dissections classified?

By site of involvement, proximal (A) and distal (B), DeBakey I, II, III

  • I – ascending and descending
  • II – ascending only
  • III – descending only (better prognosis)

Pass Criteria:

  • Bold to pass

What are the potential consequences of the disease?

  • Rupture back into intima or out through adventitia
  • Most common cause of death is rupture into pericardial, pleural or peritoneal cavities
  • Other outcomes include cardiac tamponade, aortic insufficiency, MI, extension into any of the branches of the aorta causing obstruction +/- ischaemia, transverse myelitis

Pass criteria:

  • 3 to pass

Q23

What are the causes of Aortic valve stenosis?

  • Postinflammatory scarring (Rheumatic fever)
  • Senile calcific Ao Stenosis
  • Calcification of congenitally deformed valve

Pass criteria:

  • 2 out of 3 to pass

What is calcific aortic stenosis?

  • Ao Stenosis most common valvular abnormality
  • Wear and tear => calcification on normal or cong bicuspid valves
  • Clinical attention in 6-7th decade in bicusid valves, 8-9th decade in prev. normal valves
  • Heaped up calcified masses within cusps=> protrude through to outflow tracts. Functional valve area decreased

Pass Criteria:

  • Bold to pass

What are the consequences of calcific aortic stenosis?

  • LV outflow obstruction=> increased pressure gradient over valve. (severe when valve area 0.5-1cm2)
  • CO maintained by concentric LVH. Hypertrophied myocardium ischaemic.
  • Impaired systolic and diastolic function.
  • Decompensation => angina, CCF, syncope

Pass criteria:

  • Bold to pass

Q24

What are the causes of acute pericarditis?

  • Infectiousviral, pyogenic bacteria
  • Immune mediated(presumed); Rheumatic fever, SLE, Scleroderma, post cardiotomy. Post MI (Dressler’s), Drug hypersensitivity reaction.
  • Other; AMI, uraemia, post cardiac surgery, neoplastic, trauma, radiation

Pass criteria:

  • Need viral and three others

What types of pericardial fluid exudate occur?

  • Serous; usually non-infectious inflammation, RF, SLE, uraemia, tumours
  • Fibrinous/serofibrinous; (most common) post MI, Dressler’s, trauma, post surgery but also as in 1.
  • Purulent/suppurative; almost always bacterial invasion from local infection, lymphatic or blood seeding, or at operation
  • Haemorrhagic
  • Caseous

Pass Criteria:

  • 2/5 to pass

Describe the clinical features of pericarditis.

  • Pericardial rub (may be absent if large effusion).
  • Pain, fever (chills and rigors if suppurative)
  • Signs of cardiac failure

Pass criteria:

  • Rub, pain, fever required

Q25

Outline the steps involved in the pathogenesis of atherosclerosis.

Response to injury hypothesis:

  • Endothelial injury and dysfunction
  • Lipoprotein (mainly LDL) accumulation and oxidation in vessel wall
  • Monocyte adhesion and migration into intima and transformation into foam cells and macrophages
  • Platelet adhesion
  • Smooth muscle cell migration from media into intima
  • Subsequent smooth muscle cell proliferation in intima
  • Enhanced lipid accumulation within intimal cells (macrophages and smooth muscle cells)

Pass criteria:

  • Bold to pass

List the potential causes of endothelial injury?

  • Hyperlipidaemia,
  • Hypertension,
  • Smoking
  • Haemodynamic factors (disturbed flow patterns)
  • Homocysteine, 6. Toxins, 7. Viruses, 8. Immune reactions

Pass Criteria:

  • 3 bold PLUS 1 other

Q26

Classify haemolytic anaemias.

  • Intravascular/extravascular OR
  • Extrinsic/intrinsic to the RBC OR
  • Hereditary/acquired

Pass criteria:

  • One classification

Describe the common features of haemolytic anaemias.

  • *Decreased RBC life span(< 120/7) due to premature destruction
  • ^ erythropoietin and erythropoiesis
  • Accumulation of products of Hb catabolism
  • Reticulocytosis

Pass Criteria:

  • Premature RBC destruction and one other feature

Give some important causes of intravascular haemolysis.

  • Mechanical injury: cardiac valves, microangiopathic. repetitive physical trauma
  • Complement fixation: ABO incompatible blood transfusion
  • Intracellular parasites: malaria
  • Exogenous toxins: clostridia

Pass criteria:

  • 2 out of 4

Apart from anaemia what are the results/manifestations of intravascular haemolysis?

  • *Haemoglobinaemia
  • Haemoglobinuria
  • *Unconjugated hyperbilirubinaemia( jaundice) from catabolism of haem groups in mononuclear phagocyte system
  • Haemosiderinuria and renal haemosiderosis
  • Decreased serum haptoglobin due binding with free Hb and then cleared by monophag system.
  • Free Hb oxidized to metHb
  • Reticulocytosis

Pass criteria:

  • * Hbaemia and hyperbilirubinaemia to pass and one other
  • OR 3 of 7

Q27

What major clinical disorders are associated with DIC?

  • Most common are obstetric complications, malignancy, sepsis and major trauma
  • Obstetric: abruptio, retained dead fetus, amniotic fluid embolism, septic abortion.
  • Infections:  G-ve sepsis, meningococcus, malaria, rickettsia, histoplasmosis, aspergillosis
  • Neoplasia: pancreas, prostate, lung, stomach.
  • Massive tissue injury: trauma, burns, surgery.
  • Miscellaneous:  snakebite, shock, heat stroke, vasculitis, liver disease, leukaemia.

Pass criteria:

  • 3 of 5 groups and an example of each

What is the pathogenesis of DIC?

  • 2 major mechanisms
    • release of tissue factor or thromboplastic substances into the circulation, shift towards pro-coagulation, extrinsic pathway
    • widespread injury to epithelial cells, causing release of tissue factor, platelet aggregation, intrinsic coag pathway

Pass Criteria:

  • Both mechanisms to pass

What are the consequences of DIC?

  • Widespread deposition of fibrin leads to ischaemia and haemolytic anaemia
  • Hemorrhagic diathesis (consumptive coagulopathy) from consumption platelets/clotting factors & activation plasminogen

Q28

What is sickle cell disease?

  • Hereditary haemoglobinopathy
  • (Generally heterozygous (about 40% HbS) is asymptomatic unless severe hypoxia.
  • Homozygous most haemoglobin is HbS – leads to alteration of the Hb when deoxygenated – sickling (morphological alteration),  as well as red cell membrane changes)

Pass criteria:

  • An abnormal haemoglobin HbS is formed because of a point mutation in the beta globin chain

What are the major clinical features of sickle cell disease?

  • Haemolytic anaemia (anaemia, reticulocytosis, hyperbilirubinaemia)
  • Vaso- occlusive complications/crises
  • Splenomegaly/dysfunction
  • Prone to infections esp pneumococcus/haemophilus

Pass criteria

  • 2 minimum

What are the major precipitants for a sickle cell crisis in a prone individual?

  • Hypoxia
  • Dehydration
  • Drop in pH

Pass criteria:

  • 2 out of 3

Q29

What is Disseminated Intravascular Coagulation?

  • Intravascular activation of the coagulation sequence by a variety of processes and clinical conditions
  • Resultant formation of micro-thrombi throughout the circulation, often unevenin distribution
  • Consumption of platelets, fibrin & coagulation factors
  • Coagulopathy secondary to loss of platelets, fibrin & coagulation factors
  • Activation of fibrinolytic mechanisms aggravates haemorrhagic potential
  • Clinical picture of tissue/organ hypoxia/infarction as well as haemorrhage
  • Microangiopathic haemolytic anaemia (MAH) secondary to intravascular fibrin traumatising RBC

Pass criteria:

  • Bold to pass

List the major clinical disorders associated with DIC.

Obstetric:

  • Abruption
  • Retained dead fetus
  • Septic abortion
  • Amniotic fluid embolus
  • Toxaemia

2. Infection/Sepsis

  • Meningococcaemia
  • Malaria
  • Gram negative sepsis
  • Aspergillosis
  • Histoplasmosis

3. Neoplasm

  • Ca pancreas, prostate, lung & stomach
  • Acute promyelocytic leukaemia

4. Trauma

  • Major diffuse
  • Burns
  • Extensive surgery
  • Other:
    • Liver disease
    • Heat stroke
    • Shock
    • Snakebite
    • AAA

Pass Criteria:

  • Need two from at least 4 groups

What are the major mechanisms which trigger Disseminated Intravascular Coagulation?

  • Pathological activation of the extrinsic and/or intrinsic coagulation pathways. OR impairment of clot-inhibition (RARE)
  • 1. Release of tissue factor or thromboplastic substances into the circulation (placental origin in obstetric disorders; mucus from adenocarcinoma; endotoxins in gram negative sepsis)
  • 2.  Widespread / diffuse injury to endothelial cells (TNF is extremely important mediator), seen with heat stroke, burns, diffuse trauma, meningococcal & rickettsial infection

Pass criteria:

  • Bold PLUS 1 other

Q30

What are the proposed pathogenesis and consequences of pre-eclampsia?

Placental ischaemia is the key feature leading to

  • Reduction in PGI2, PGE2,
  • Inc renin/angiotensin II,
  • Inc thromboxane and endothelial dysfunction,
  • Resulting in systemic hypertension & DIC

Pass criteria:

  • Placental ischaemia PLUS 1 other point

Describe the clinical course of pre-eclampsia?

  • Usually starts after 32 weeks gestation, charcaterised by 1.Hypertension, oedema and proteinuria.
  • Headache and visual disturbances are common.
  • Ecclampsia is characterised by convulsion and coma

Pass Criteria:

  • 2 out of 3 to pass

Describe the morphological changes in the placenta?

  1. Placental infarcts,
  2. retroplacental haematoms,
  3. villous ischaemia,
  4. prominent syncytial knots,
  5. thickened trophoblastic basement membrane,
  6. villous hypovascularity,
  7. fibrinoid necrosis
  8. intramural lipid deposition.

Pass criteria:

  • 3 to pass

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