Q31

List the major risk factors for aortic dissection?

  • Hypertension
  • Connective tissue diseases eg. Marfan Syndrome,
  • Iatrogenic:  coronary artery catheterisation, Coronary artery by pass.
  • Pregnancy

Pass criteria:

  • Bold PLUS 1 other point

Describe the morphological features of aortic dissection.

  • Most frequent pre-existing = medial degeneration of  elastic tissue
  • Intimal tear aorta extends into the media.
  • Haematoma spread between the middle and outer thirds along the laminar planes of the media and formed a blood filled channel.
  • Disrupts outward causing massive haemorrhage or  re-rupture into the lumen of the aorta producing a false lumen.

Pass Criteria:

  • At least 2

What are the consequences of aortic dissection?

  • Dissects proximally towards the aortic valve and vessels of the neck and causes disruption of the aortic valve, cardiac tamponade, myocardial infarction, cerebral vascular accident.
  • Dissects distally into the renal, mesenteric, iliac & femoral arteries causing ischaemia.
  • Compression of the spinal vessels causing transverse myelitis.

Pass criteria:

  • 1 proximal
  • 1 distal
  • PLUS 1 other

Q32

Describe the formation of a primary haemostatic plug after vascular injury.
Prompt: What is the role of platelets at the site of injury?

1.            Circulating platelets exposed to extracellular matrix (esp collagen) resulting in adhesion via vWf /Gp1b/V/IX.

2.            Activation — a) Secretion of granule contents (esp Ca— and ADP from dense granules) and b) expression phospholipids with platelet thromboxane A2 leads to

3.            Aggregation = primary haemostatic plug (reversible process)
Pass: Need 3/3 Bold

How does this then become the secondary haemostatic plug?

1.            Thrombin binds to platelet with ADP/TxA2 – increased aggregation

2.            Platelet contraction occurs (“viscous metamorphosis”) = secondary haemostatic plug

3.            Fibrin formation locks platelets into clot (irreversible process)

Pass: Need 2/3 bold

 


Q33

What are the haematological and clinical effects of von Willebrand disease?

Haem;   Increased bleeding time with normal platelets

Increased PT time (Types 1 & 3) Decreased Ristocetin cofactor activity

Clin:       Spontaneous bleeding from mucous membranes

Increased bleeding from wounds

Menorrhagia

Bleeding into joints rare except in Type 3

Pass: Need 3/4

Describe the types of von Willebrand Disease.

1.            Type 1 and Type 3 associated with decreased circulating vWF. Type 1 most common (70%), autosomal dominant and usually mild. Type 3 autosomal recessive and severe

2.            Type 2 has defective vWF, autosomal dominant, mild severity and 25% of cases.

Pass: Need 2/3

 


Q34

What are the characteristics of hypertrophic cardiomyopathy?
Prompt: What are the structural effects on the myocardium?

1.            Myocardial hypertrophy without ventricular dilatation

2.            Asymmetrical septal thickening (septum >> free wall)

3.            Impaired diastolic filling and LV outflow obstruction in 25% of cases

Pass: Need Bold

What are the complications of HCM?

1.            Heart Failure

2.            Sudden death, ventricular arrhythmias

3.            Atrial fibrillation, mural thrombus / ernbolisation

4.            Stroke

5.            Infective endocarditis mitral valve

Pass: Need 3/5


Q35

What is the sequence of events in acute coronary artery occlusion?
Prompt: What happens to an atheromatous plaque to initiate acute coronary occlusion?

  1. Atheromatous plaque rupture / erosion
  2. Platelet adhesion, activation and aggregation, with release of aggregators (Thromboxane, serotonin and platelet factors)
  3. Vasospasm
  4. Intrinsic coagulation cascade activation

Thrombus evolves to occlude artery

Pass: General outline of plaque rupture, platelet aggregation and thrombus formation = Red thrombus

Describe the time course of myocardial injury after coronary occlusion.
Prompt: When does irreversible cell injury occur?

1.            ATP depletion — seconds

2.            Loss of contractility-2 mins

3.            ATP reduction — 10-40 mins

4.            Irreversible cell injury — 20-40 mins

5.            Myonecrosis begins after —30 mins

6.            Microvascular injury at 1 hour

7.            Extensive necrosis needs 2-4 hours of ischaemia (blood flow < 10%)

Anaerobic metabolism begins immediately; cell death occurs begins after half an hour or so; extensive necrosis occurs after 2 hours.

Pass: Minutes to hours concept


Q36

What is Von Willebrand's Disease?

Bleeding disorder

Compound defect in platelet function and the coagulation pathway- VWf factor VIII complex

Type 1— mild quantitative reduction in circulating vWF

–              commonest sub-type (70%)

–              autosomal dominant

–              relatively mild clinical syndrome

Type 2 – qualitative defect in vWF

–              autosomal dominant

–              10-15% of cases

–              mild to moderate bleeding syndrome

Type 3 – marked quantitative reduction in circulating vWF

–              relatively rare

–              autosomal recessive

–              severe clinical picture

Pass: Combination platelet and coagulation abnormality required.

Clinical scenario is one of...

i)             mucous membrane bleeding

ii)            excessive wound bleeding

iii)           menorrhagia

iv)           increased bleeding time

v)            Bleeding into joints occurs with the more severe types only.

What are the effects on the clotting?

  • Prolonged bleeding time and normal platelet count, possibly increased partial thromboplastin time (PTT)
  • Either quantitative or qualitative deficiency in VWf leading to factor VIII dysfunction
  • Main function is facilitation of adhesion of platelets to subendothelial collagen in haemostasis
  • Increases the half-life of factor VIII from 2.5 to 12 hours

Q37

What are some of the causes of dementia?

Alzheimer’s disease is commonest

Frontotemporal dementia

Multi-infarct dementia (vascular)

Parkinson’s disease (Lewy bodies)

Creutzfeld-Jakob disease

Neurosyphilis, toxins etc

Pass: Bold and two others

Can you describe the pathogenesis of Alzheimer's disease?

Lysis of transmembrane protein Amyloid Precursor Protein by beta and gamma secretases produces AO & C-terminal portion of APP

Ap peptides aggregate into amyloid fibrils and can be directly neurotoxic

C-terminal portion of APP involved in cell signalling and transcription regulation

Severity of Alzheimer’s disease is related to loss of synapses

Pass: Required amyloid generation


Q38

What are the different types of cardiomyopathy?

  1. Dilated
  2. Hypertrophic
  3. Restrictive

Pass: At least 2

What are the pathological features of hypertrophic cardiomyopathy?

  1.  Macroscopic: hypertrophy without dilatation, asymmetric (sub-aortic), LV outflow
  2.  Microscopic: myocyte hypertrophy, disarray of myocytes, interstitial fibrosis

Pass: At least 2

What is the complications of HOCM?

  1. AF
  2. CCF
  3. Sudden death

Q39

How is the coagulation cascade limited to the site of vascular injury?
Prompt: What natural anticoagulants?

  1. Exposed phospholipids at site necessary for factor activation.
  2. Natural anticoagulants generated:
    1. Antithrombins by binding to endothelial cell
    2. Proteins C and S, via thrombomodulin
    3. Plasmin via endothelial cell release tPA
    4. (FDPs also weakly anticoagulant)
    5. Tissue factor pathway inhibitor

Q40

What are the potential fates of an intravascular thrombus?

Propagation Embolisation

Dissolution Organisation\Recanalisation

What are the primary causes of a hypercoagulable state?
Prompt: '1° = genetic or inherited' if need be

Factor V (Leiden) mutation

Antithrombin 111 deficiency

C or S deficiency

Other: Homocysteinaemia, Fibrinolysis defects, Increased prothrombin


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