↓ RBC number (usually measured as ↓ Hb conc. in blood)↓ oxygen capacity of the blood

6.0 Vascular Disease Flashcards by Toby Charles

Define anaemia:

↓ RBC number (usually measured as ↓ Hb conc. in blood) ↓ oxygen capacity of the blood

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What is the lifespan of RBCs?

120 days

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Structure of haemoglobin:

Tetramer 2 pairs of polypeptides (each with haem group)

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What Hb chains are present in fetal Hb?

α2γ2

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What Hb chains are present in adult Hb (major form)?

α2β2

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What Hb chains are present in adult Hb (minor form)?

α2δ2

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Clinical consequences of anaemia:

1) Ectodermal changes - Thin skin + nails - Pale mucosa 2) Hypoxic damage in viscera - Angina, malaise, fatigue, dim vision, faintness 3) Compensatory changes - ↑ HR + CO - ↑ Breathing rate - Hyperplasia of haemopoietic tissue in bone marrow

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Why do the cells increase in size in megaloblastic anaemia?

Cause of this anaemia is impaired DNA synthesis This means the cell does not divide but RNA and protein synthesis continue → ↑ size

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What changes are seen in megaloblastic anaemia?

1. Ineffective haemopoiesis - ↓ RBC, granulocytes and platelets (pancytopenia) 2. Expansion of haemopoietic tissue 3. RBC precursors enlarged (megaloblasts) - May appear in the blood 4. RBC enlarged (macrocytosis) and oval shaped 5. RBC different sizes (anisocytosis) and shapes (poikilocytosis) 6. Iron cannot be utilised normally - Deposited in various organs 7. Effects in other cells and tissues - Neutrophils and megakaryocytes large with hypersegmented nuclei - Enlarged nuclei in gut epithelial cells - etc

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How long does B12 stay stored in liver for?

5 years

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What two deficiencies cause megaloblastic anaemia?

1) Vit B12 deficiency 2) Folate deficiency

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What does iron deficiency anaemia cause a defect in?

Haem synthesis

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What does thalassaemia cause a defect in?

Globin synthesis

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2 types of haemolytic anaemia:

1) Extravascular (removed by macrophages, mainly in spleen) 2) Intravascular

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What abnormalities cause haemolytic anaemia?

1) Intrinsic to RBCs (hereditary) - Structural defects (hereditary spherocytosis) - Enzyme defects (pyruvate kinase ↓) - Haemoglobinopathies 2) Extrinsic to RBCs (acquired) - Immune (Haemolysis Dx of newborn) - Physical (valve replacement) - Chemical (lead poisoning) - Infection (malaria)

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What is the amino acid switch in sickle cell disease?

HbS (α2β2 6 glu ⟶ val)

Two types of thalassaemia?

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What are platelets formed from?

Megakaryocytes

Life span of platelets?

7 days

What do platelets use to adhere to collagen?

vWF

What do platelets secrete once activated?

1) Thromboxane A2 2) Vasoactive amines (5-HT) 3) ADP These cause vasoconstriction and platelet aggregation

What molecules mediate primary haemostats plug?

1) Integrins (α₁₁bβ₃) 2) Junctional adhesion molecules (JAMs) 3) Endothelial cell-specific adhesion molecules (ESAM) 4) Eph + Ephrin families

What factors on normal endothelial cells inhibit haemostasis?

1) NO (↓ platelet activation) 2) PGI2 (prostacyclin) (↓ platelet activation) 3) Antithrombin (on cell surface. Binds to thrombin and inactivates it. Complex is then cleared by liver) 4) Tissue factor pathway inhibitor (TFPI) (blocks factor X) 5) Thrombomodulin (conformational change to thrombin → ↓ fibrin activation and ↑ protein C activation) 6) Protein C (↓ factor V + VIII) 7) Protein S (cofactor for protein C)

What are Virchow’s triad?

1) Changes in vessel wall 2) Changes in blood flow 3) Changes in blood constituents

Structure of thrombi in arteries/cardiac chambers:

Compact
Granular
Firm
Lines of Zahn

Structure of thrombi in veins:

Pale head (fibrin + platelets)
Long red tail (enmeshed RBCs)

Three layers of vessel?

Tunica intima
Tunica media
Tunica adventitia

Define atherosclerosis:

Disease of intima of large and medium sized arteries

Lesions = focal thickenings of intima (plaques)
These are deposits of fibrous tissues and lipids

Arteriosclerosis

Loss of elasticity and physical hardening of the arterial wall from any cause

Often accompanied by calcification of the wall

≠ atheroscleosis

Do deficiencies in the following components of lipoprotein pathways cause and increase or decrease in atherosclerotic lesions?

1) apoE
2) LDL receptor
3) SR-A
4) CD36
5) Acyl-cholesterol acyl transferase (ACAT)

1) apoE → ↑
2) LDL receptor → ↑
3) SR-A (scavenger protein) → ↓
4) CD36 (scavenger protein) → ↓
5) Acyl-cholesterol acyl transferase (ACAT) → ↓

What are key changes in the vessel wall that cause atherosclerosis?

1. Endothelial cell injury/dysfunction
2. Monocyte migration into the plaque and maturation into macrophages
3. Smooth muscle cell activation
4. Lipoprotein infiltration
5. T-lymphocyte migration into the plaque
6. Platelet adherence

Where do pale infarcts occur?

Solid tissues (heart, kidney, spleen)

Where do red infarcts occur?

1) Arterial occlusion
Spongy tissues (lung)
Tissues with collateral blood supply (gut)

2) Venous occlusion