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BOD MVST 1b > Vascular > Flashcards

Vascular Flashcards

1
Q

Define haemostasis

A

Haemostasis is the physiological response of blood vessels to injury, with the aim of preventing blood loss. Cooperation of platelets, proteins of coagulation cascade, and endothelial cells.

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2
Q

Define thrombosis

A

Inappropriately activated haemostasis

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3
Q

Define platelet

A

Discoid anuclear body produced by cytoplasmic fragmentation of megakaryocytes in bone marrow

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4
Q

What is the lifespan of a platelet?

A

7 days

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5
Q

What mediates platelet adherence to collagen?

A

Von Willebrand factor

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6
Q

What signals do platelets secrete after they adhere to collagen?

A

chemical signals thromboxane A2, vasoactive amines 5HT, ADP

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7
Q

Which factors mediate platelet contraction and fusion?

A

Integrins esp alpha IIb beta3
JAMs Ig-Super-Family junctional adhesion molecules
ESAM endothelial cell-specific adhesion molecule
Kinase-ligand combination of eph and ephrin families

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8
Q

What do the integrins and eph/ephrins do?

A

signalling molecules. Cytoskeletal alterations (myosin dependent contraction) responsible for retraction of blood clot

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9
Q

What is purpura?

A

Bleeding from skin capillaries due to reduced platelet number

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10
Q

What is the primary haemostatic plug?

A

Platelets aggregated together with sufficient internal cohesion to resist dissolution by force of blood

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11
Q

What is the secondary haemostatic plug?

A

Fibrin strands created by the coagulation cascade making a meshwork with fused platelets

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12
Q

Which inhibitors of haemostasis do endothelial cells produce?

A
  1. NO, prostacyclin PGI2 which inhibit platelet aggregation
  2. Antithrombin – binds and inactivates thrombin. Antithrombin-thrombin complexes cleared in liver
  3. Tissue factor pathway inhibitor – blocks activation of factor X by tissue factor
  4. Thrombomodulin – changes conformation of thrombin so it is less able to cleave fibrinogen during coagulation cascade, instead activates protein C which inactivates factors V and VIII
  5. Protein S cofactor for protein C
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13
Q

How do damaged cells promote haemostasis?

A

Exposed tissues activate platelets and coagulation cascade
Synthesise
1. Von Willebrand factor
2. Tissue factor
3. Express binding sites that increase activity of coagulation factors IX and X

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14
Q

Define thrombus

A

Mass formed from blood constituents within the circulation during life. Fibrin and platelets, with entrapped red and white blood cells.

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15
Q

Define blood clot

A

Formed in static blood, involves predominantly the coagulation system without interaction of platelets with the vessel wall e.g. post mortem. Random mixture of blood cells suspended in serum proteins

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16
Q

Compare and contrast the structure of blood clots and thrombi

A

Blood clot = soft, jelly-like and unstructured.
Arterial thrombus = compact, granular, firm. Contain laminations of pale layers of fibrin/platelets, and dark layers with more erythrocytes. Lines of Zahn.
Venous thrombus = pale head with little evidence of lamination, still platelets and fibrin. Red tail due to many enmeshed red cells (going towards the heart)

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17
Q

What causes changed flow in arteries/cardiac chambers and veins?

A

Arteries/cardiac chambers = turbulence (narrowing/aneurysms/MI/arrhythmia/valvuar disease)
Veins = stasis (right heart failure, immobilisation, compressed veins, varicose veins, increased viscosity of blood)

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18
Q

Which veins are most commonly thrombosed?

A

Pelvic and deep and superficial leg veins

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19
Q

What does antithrombin III do?

A

Inhibit haemostasis

XIIa, XIa, IXa, XIIIa, Xa, thrombin?

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20
Q

What does protein C do?

A

Inhibit factor V and VIII

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21
Q

What does thrombomodulin do?

A

Inhibit thrombin from converting fibrinogen to fibrin

Allow thrombin to activate protein C

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22
Q

What are the lines in thrombi called and what are they?

A

Lines of Zahn
Dark = erythrocytes
Light = fibrin and platelets

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23
Q

Define embolus

A

Intravascular solid, liquid, or gaseous gas carried by blood flow from its point of origin to impact at a distant site.

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24
Q

Where do most emboli lodge?

A

Systemic veins e.g. leg and pelvis or right side of heart –> pulmonary artery
Left side of heart and aorta –> systemic arterial system –> brain, spleen, kidney, gut, legs etc.

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25
Q

What can infected emboli cause?

A

Pyaemia (septicaemia) with abscess formation where they lodge

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26
Q

What can a pulmonary embolus cause?

A

Hypoxia, P infarction, reduced CO, right heart failure, shock, death

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27
Q

What are the 3 layers of an arterial wall and briefly describe them?

A
  1. Intima: endothelium and basement membrane
  2. Media: layers of perforated elastic laminae with smooth muscle cells between. Bounded by internal and external elastic laminae.
  3. Adventitia: connective tissue, fibroblasts, macrophages, nerves, lymphatic, vasa vasorum supplying the artery wall.
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28
Q

What is the lifetime of an endotheial cell?

A

> 5 years

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29
Q

What type of artery is the aorta?

A

Large

Elastic

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30
Q

What type of artery are coronary arteries?

A

Medium

Muscular

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31
Q

Define atherosclerosis

A

Disease of the intima of large and medium sized arteries

Lesions are focal thickenings of the intima called plaques– deposits of fibrous tissues and lipids

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32
Q

Define arteriosclerosis

A

Loss of elasticity and physical hardening of the arterial wall from any cause, often associated with calcification of the wall

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33
Q

What are the major positive risk factors for atherosclerosis?

A
  1. Hyperlipidaemia
  2. Smoking cigarettes
  3. Hypertension
  4. Diabetes mellitus
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34
Q

What are the minor risk factors for atherosclerosis?

A
  1. Age
  2. Family history
  3. Male
  4. High fat diet
  5. Stressful and sedentary lifecycles
  6. Obesity
  7. Alcoholism
  8. Low birth weight
  9. Low socioeconomic status
  10. Infections (maybe chlamydia)
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35
Q

What are the negative risk factors for atherosclerosis?

A
  1. High levels HDL
  2. Moderate alcohol consumption 2 units/day
  3. Cardiovascular fitness
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36
Q

How do lipoproteins transfer the lipids they carry into cells?

A
  1. LDL receptor pathway - responsible for cholesterol breakdown.
  2. Scavenger receptor pathway - macrophages take up lipoproteins that have been modified, leads to uncontrolled accumulation of cholesterol. Then macrophages called foam cells.
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37
Q

What are foam cells?

A

Macrophages that have taken up a fuckton of lipoproteins via the scavenger receptor pathway

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38
Q

What is dyslipoproteinaemia?

A

Abnormality in the constitution/concentration of lipoproteins in the blood

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39
Q

What causes dyslipoproteinaemia?

A
  1. Familial - FH (mutations in LDL receptor pathway)

2. Secondary - diabetes mellitus, hypothyroidism

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40
Q

Which genetically engineered mice developed advanced atherosclerotic lesions?

A

ApoE or LDL receptor deficient

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41
Q

Which genetically engineered mice had reduced development of atherosclerosis?

A

Deficient for scavenger receptors SR-A or CD36 (moderate reduction)

Mice that cannot store cholesterol due to deficiency in ACAT acyl-cholesterol acyl-transferase

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42
Q

How does atherosclerosis develop?

A
  1. Endothelial cell injury or dysfunction
  2. Monocyte migration into plaque and maturation into macrophages
  3. Smooth muscle cell activation
  4. Lipoprotein infiltration
  5. T lymphocyte migration into the plaque
  6. Platelet adherence
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43
Q

How does endothelial cell injury or dysfunction lead to atherosclerosis?

A

• Haemodynamic forces (hypertension, branch points) chemical injury (cigarette smoke, oxidised lipoproteins)

increased conc LDL – at high concs toxic, at low concs angiogenesis, increased permeability so increased lipid infiltration, increased adhesion molecule expression (P and E selectin, VCAM-1, ICAM-1), increased chemokine/mitogen expression (MCP-1 monocyte chemoattractant protein), IL1 and IL8, increased LDL oxidation, increased thrombosis

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44
Q

How does monocyte migration lead to atherosclerosis?

A

Develop into macrophages and become foam cells. Increase MCP-1 expression and chemokine receptor expression CCR2 and CXCR2, present antigen to T cells, activate endothelial cells via IL1 TNFalpha VEGF, oxidise and uptake lipids via scavenger receptors, activate smooth muscle cells via PDGF and ROS, modify matrix with collagenase, promote coagulation through release of tissue factor

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45
Q

How does activating smooth muscle contribute to atherosclerosis?

A

macrophages, platelets and endothelial cells –> PDGF, FGF, ROS –> activate vascular smooth muscle cells –> proliferate –> migrate into intima –> change into a matrix producing synthetic phenotype (from a contractile phenotype)  secrete ECM –> release enzymes like collagenase that assist in matrix remodelling.

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46
Q

How does lipoprotein infiltration contribute to atherosclerosis?

A

LDL oxidised in plaques by ROS intermediates and enzymes released by platelets, macrophages and endothelial cells. Oxidised lipoproteins chemoattractant for monocytes, phagocytosed by macrophages which become foam cells, stim plaque cells to release cytokines and growth factors, induce dysfunction/apoptosis in smooth muscle, macrophages and endothelium, may be immunogenic, inhibit plasminogen activation

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47
Q

Name a couple of anti-oxidants

A

Vitamin E, NO

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48
Q

How does T-lymphocyte infiltration into the plaque contribute to atherogenesis?

A

May recognise Ag such as oxidised lipoproteins, and subsequently activate immune responses and cytotoxic killing of cells in the plaque

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49
Q

How does platelet adherence contribute to atherogenesis?

A

Early: platelets adhere transiently to the injured epithelium and release PDGF platelet derived growth factor which can activate smooth muscle cells
Advanced lesions: also involved in thrombosis that occurs if plaques ulcerate or rupture

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50
Q

What are fatty streaks?

A

Found from second decade of life throughout the vascular tree
Microscopically are clusters of lipid-laden smooth muscle cells and foam cells
No significant pathology themselves

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51
Q

What are fibro-fatty atherosclerotic plaques?

A

Raised white-yellow plaques that may coalesce
Microscopically media atrophic/thinned with 3 regions
1. Fibrous cap on extreme intimal surface of plaque
2. Lipid core
3. Shoulder

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52
Q

What makes up the fibrous cap?

A

Collagen, smooth muscle cell, mphages, T lymphocytes

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53
Q

What makes up the lipid core?

A

Foam cells, in more advanced lesions necrotic debris and extracellular lipid (especially cholesterol)

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54
Q

What makes up the shoulder?

A

The shoulder of the cap

Foam cells, smooth muscle cells, T cells, new blood vessels (angiogenesis)

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55
Q

What can complicate a plaque?

A
  1. Calcification
  2. Haemorrhage from new vessels
  3. Rupture/ulceration esp if plaque rich in leucocytes or show haemorrhage –> thrombolism or embolization
  4. Aneurysms due to thinning of intima
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56
Q

What are the important consequences of atherosclerosis?

A

Ischaemic heart disease –> angina, MI, cardiac failure
Peripheral vascular disease –> intermittent claudication and gangrene
Cerebrovascular disease –> transient ischaemic attacks and stroke
Aneurysms
Renal failure

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57
Q

Define ischaemia

A

Inadequate local blood supply to an organ (so an insufficient quantity of blood)

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58
Q

Define infarction

A

Necrosis due to ischaemia

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59
Q

What are the causes of ischaemia?

A
  1. External occlusion of vessels, e.g. tumours, compression
  2. Internal stenosis or occlusion, e.g. atherosclerosis, thrombosis, embolism
  3. Spasm of vessel, e.g. frost bite due to cold
  4. Capillary blockage, e.g. sickle cell, cerebral malaria
  5. Shock
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60
Q

Define shock

A

Circulatory failure with low ABP

Causes impaired perfusion

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61
Q

What are the 4 types of shock?

A
  1. Cardiogenic
  2. Hypovolaemic
  3. Septic
  4. Anaphylactic
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62
Q

List tissues in decreasing order of sensitivity to ischaemia

A
  1. Neurons (3 min)
  2. Renal PT epithelium
  3. Myocardium (20 min)
  4. Skeletal muscle - less sensitive, capable of anoxic work
  5. Fibroblasts and macrophages (insensitive)
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63
Q

What decides the susceptibility of organs to ischaemia?

A
  1. Collateral circulation reduces susceptibility, may be there normally or may develop if slowly progressing arterial narrowing
  2. Dual blood supply e.g. lungs pulmonary and bronchial, liver hepatic portal vein hepatic artery, brain circle of Willis
  3. Single/functional end arteries very susceptible to ischaemia e.g. kidney, spleen
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64
Q

What decides the outcome of ischaemia?

A
  1. Anatomy of blood supply to organ
  2. Size of block
  3. Degree of block
  4. Speed of onset
  5. Persistence of block
  6. Vulnerability of tissue
  7. Demand of tissue (e.g. angina on exertion)
  8. General adequacy of circulatory system)
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65
Q

What is the outcome of ischaemia?

A

Can have

  1. No effect
  2. Functional defects e.g. dysrhythmia, renal insufficiency
  3. Reversible cell damage e.g. cell swelling, fatty change in myocardium and hepatocytes
  4. Infarction
  5. Ischaemic reperfusion injury
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66
Q

Where does fatty change occur in myocardium and hepatocytes?

A 
Myocardium = sub-endocardial zone
Hepatocytes = centrilobular region
67
Q

When do infarcted tissues show histological changes?

A 
4-12 hours coagulative necrosis
24h acute inflammation at viable margins
3-5 days macrophages appear 
7-10 days granulation tissue
6-8 weeks infarct replaced by non-functional fibrous scar
68
Q

What is the name of the microscopic appearance shown in infarcted tissues? What does it look like and why?

A

Coagulative necrosis
Eosinophilia of cytoplasm (denatured cytoplasmic proteins, loss of cytoplasmic RNA)
Karyolysis, pynknosis or karyorhexis

69
Q

Define karyolysis

A

Pale nucleus

70
Q

Define pyknosis

A

Shrunken nucleus

71
Q

Define karyorhexis

A

Fragmented nucleus

72
Q

What are the different types of infarct?

A

Haemorrhagic
Pale
Septic
Cystic

73
Q

What do acute infarcts look like macroscopically?

A

Red and poorly defined - capillary dilation and haemorrhage

74
Q

What do pale infarcts look like and what are they?

A

Solid tissue infarcts
Prevents too much blood entering the tissues
Heart, kidney, spleen
Within 24h red margins, fibrinous exudate on surface

75
Q

What are red infarcts?

A

Infarcts that remain red due to haemorrhage e.g. arterial or venous occlusion

76
Q

What defines the shape of an infarct?

A

The blood supply to the tissue. Usually cone-shaped with apex at point of occlusion and base at organ surface. Wedge-shaped in 2D

77
Q

What is a septic infarct?

A

An infarct that can become secondarily infected, e.g. in lung. Can progress to an abscess

78
Q

What is a cystic infarct?

A

In the brain, infarcts undergo liquefactive necrosis. Necrotic cells digested quickly, form a cyst containing liquid, surrounded by reactive glial cells.

79
Q

What is ischaemic reperfusion injury?

A

When restoring blood flow to a tissue converts reversible injury to irreversible injury
Thought to be due to fresh mediators of cell injury, e.g. free radicals, Ca2+, or initiation of acute inflammation by delivery of neutrophils and complement

80
Q

What causes myocardial infarction?

A

Coronary artery atherosclerosis complicated by thrombosis

81
Q

What does MI affect?

A

Left ventricle
Dysrhythmia, sudden death, cardiogenic shock, rupture of the infarct, mural thrombosis on endocardium overlying the infarct, scarring may lead to aneurysm, adaptation to inadequate cardiac output - dilation or hypertrophy, cardiac failure

82
Q

What causes pulmonary infarction?

A

Thromboembolism from pelvic or leg veins

83
Q

What are the effects of pulmonary infarction?

A

Commonly red infarct
Silent if small
Impaired lung function
Pressure overload on right heart and possibly right heart failure
Infection - septic infarcts, abscess, pneumonia

84
Q

What causes cerebral infarction?

A

Cerebral artery thrombosis
Embolism from left heart or atheroma usually in common carotid
Shock

85
Q

What is the effect of cerebral infarction?

A

Liquefactive necrosis and cyst formation

Stroke - sudden onset of inadequate cerebral function

86
Q

Define anaemia

A

Reduction in the total circulating red cell mass with reduced oxygen carrying capacity of the blood

87
Q

How do you measure anaemia?

A

Reduction in haemoglobin conc

88
Q

Why does anaemia arise?

A

Imbalance between rate of production of RBCs and rate of destruction or loss

89
Q

What is the normal RBC count in men and women?

A

Men 6.5 +- 1.0 x10^12/l

Women 5.8 +- 1.0 x10^12/l

90
Q

What is the normal haemoglobin concentration in men and women?

A

16.5+-2.5 g/dl

15+-2.5 g/dl

91
Q

What is the normal size of RBCs?

A

6-9.5 micrometers

average 7 micrometers

92
Q

What are erythroid progenitors called?

A

Erythroblasts and reticulocytes

93
Q

What is the life span of an RBC?

A

120 days

94
Q

Where are RBCs destroyed?

A

Spleen

95
Q

What is the normal RBC:WBC ratio?

A

500:1

96
Q

What is the curve that shows the number and diameter of RBCs decreasing in iron deficiency anaemia?

A

Prince-Jones curves

97
Q

What is the chain makeup and percentage of total Hb of HbF?

A

alpha2 gamma2

1% adult

98
Q

What is the chain makeup and percentage of total Hb of HbA?

A

alpha2 beta2

96%

99
Q

What is the chain makeup and percentage of total Hb of HbA2?

A

alpha2 delta2

3%

100
Q

What are the symptoms and signs of anaemia?

A

Sign: skin and nails thin, mucous membranes pale
Symptoms due to hypoxic damage in viscera myocardium/kidney/liver/brain: weakness, malaise, easily fatigable, angina pectoris, headache, dimness of vision, faintness
Compensatory changes: Increased HR and CO, increased breathing rate, hyperplasia of haematopoietic tissue in bone marrow

101
Q

What are the 3 major categories of causes of anaemia?

A
  1. Impaired generation of RBC or their constituents
  2. Increased destruction of red cells
  3. Blood loss/haemorrhage
102
Q

What is dyserythropoiesis?

A

Impaired generation of RBC or their constituents

103
Q

What are anaemias caused by increased destruction of red cells caused?

A

Haemolytic

104
Q

What is aplastic anaemia?

A

A dyserythropoiesis due to little or no functional marrow

105
Q

What are anaemias with defective DNA synthesis called?

A

Megaloblastic anaemia

106
Q

What are anaemias with defective Hb synthesis called?

A

If defective haem synth = iron deficiency

If defective globin synth = thalassaemia

107
Q

What can cause megaloblastic anaemia?

A

Deficiency of B12 or B9 (folic acid), co-enzymes in thymidine synthesis

108
Q

Define pancytopenia

A

RBC, granulocytes and platelets reduced in number

109
Q

What are the changes seen in megaloblastic anaemias?

A
  1. Ineffective haemopoiesis –> pancytopenia
  2. Expansion of haematopoietic tissue
  3. RBC precursors enlarged to form megaloblasts which may appear in the blood
  4. RBCs enlarged (macrocytosis) and oval shaped
  5. RBCs different sizes and shapes
  6. Iron cant be used normally and is deposited in various organs
  7. Effects in other cells and tissues - e.g. neutrophils and megakaryocytes large with hypersegmented nuclei, enlarged nuclei in gut epithelial cells
110
Q

Define anisocytosis

A

RBCs abnormal variation in cell size

111
Q

Define poikilocytosis

A

RBCs different shapes

112
Q

What is cobalmin?

A

Vitamin B12

113
Q

What is FH4 needed for?

A

Transfer of one-carbon units, required for thymidine synthesis

114
Q

What is the minimum dietary requirement for B12?

A

1 microgram

115
Q

Where is B12 absorbed?

A

Terminal ileum, requires intrinsic factor from gastric mucosa

116
Q

How much B12 is stored in the liver?

A

Enough for 5 years

117
Q

What can cause B12 deficiency?

A
  1. Inadequate intake e.g. vegans
  2. Increased requirements e.g. pregnancy, anaemia, malignancy
  3. Malabsorption due to gastric causes - pernicious anaemia
  4. Malabsorption due to pancreatic deficiency (doesn’t make enzymes to liberate B12 from haptocorrin)
  5. Malabsorption due to ileac disease (Crohn’s)
118
Q

What is pernicious anaemia?

A

Intrinsic factor deficiency due to autoimmune destruction of gastric mucosa

119
Q

What is the function of haptocorrin?

A

Protect acid sensitive B12 from stomach acid until it reaches the small intestine where pancreatic enzymes liberate it so it can bind to intrinsic factor

120
Q

Minimum dietary requirement folate?

A

50 micrograms

121
Q

How much storage of folate do we have?

A

100 days

122
Q

What can cause folate deficiency?

A
  1. Inadequate intake e.g. elderly, chronic alcoholics
  2. Increased requirements e.g. pregnancy, malignancy, anaemia
  3. Inadequate absorption in small bowel disease e.g. coeliac
  4. Impaired utilisation e.g. methotrexate (folic acid antagonist)
123
Q

What is the IF receptor in the terminal ileum called?

A

Cubulin

124
Q

What is the normal daily requirement for iron?

A

7mg male, 15mg female

125
Q

What is the average daily dietary intake of iron?

A

15-20mg

126
Q

How is the iron storage pool kept?

A

Bound to ferritin, converted to haemosiderin if there is iron overload

127
Q

How are iron levels homeostatically controlled?

A

Regulation of iron absorption in the duodenum
-ve feedback via hepcidin, released by liver if hepatic iron levels rise
Means iron is converted to ferritin in mucosal cells which are then shed

128
Q

Causes of iron deficiency?

A
  1. Impaired absorption e.g. small bowl disease
  2. Increased demand e.g. pregnancy, childhood
  3. Chronic blood loss to exterior e.g. GI peptic ulcer/malignancy, or genitourinary malignancy
  4. Low dietary intake e.g. poverty, old age
129
Q

Which enzymes are affected in severe iron deficiency?

A

Catalase
Cytochromes
Leads to malabsorption and spoon shaped nails, thinning hair, flattened red sore tongue

130
Q

What are the two types of haemolytic anaemia?

A

Extravascular - removal by mphages in spleen, which enlarges

Intravascular - lysis within the circulation

131
Q

Define reticulocyte. What does its level in the blood show?

A

An immature red blood cell which no longer contains a nucleus, having a granular or reticulated appearance when suitably stained
Conc proportional to degree of active haematopoiesis

132
Q

What causes haemolytic anaemias?

A
  1. Red cell abnormalities - usually hereditary defect.
    Structural, enzymic, haemoglobinopathies
  2. Extrinsic abnormalities- normally acquired.
    Immune (haemolytic disease of the newborn, physical, chemical, infection
133
Q

What is hereditary spherocytosis?

A

Intrinsic abnormality of RBC due to defect in red cell skeleton that forms deformed spheroidal cells

134
Q

Which heavy metal poisoning can lead to haemolytic anaemia?

A

Lead

135
Q

What proportion of haemoglobinopathies are due to mutation?

A

90%

136
Q

What is the mutation in sickle cell anaemia?

A

Point mutation changes polar glu to + charged val on external surface of beta chain of HbS

137
Q

What causes the RBCs to sickle in homozygotes?

A

Low PO2 or pH

138
Q

What are the consequences of sickle cell anaemia?

A
  1. Haemolysis, mostly in the spleen
  2. Occlusion of small blood vessels (especially in organs with slow blood flow) with reduced O2 delivery to organs, so more sickling
  3. Tissue hypoxia/infarction can cause pain
  4. Maybe also chronic tissue hypoxia (affecting growth, kidney, lung, heart etc)
139
Q

What percent of Hb is HbS in heterozygotes?

A

40%

140
Q

What can the prevalence of sickle cell heterozygosity reach?

A

30%

141
Q

Why does sickling offer protection against malaria?

A

Increased clearance of parasitized red cells following sickling

142
Q

Define thalassaemia

A

Absent or reduced synthesis of globin chains of HbA

143
Q

What is the benefit of thalassaemia?

A

Also protects against malaria

144
Q

What are the consequences of thalassaemias?

A
  1. Reduced production of RBCs - low globin levels, red cells hypochromic, microcytic, sometimes anisocytosis
  2. Relative excess of other chain (e.g. alpa4, beta4) which precipitate as inclusions –> damage cell membrane, impair DNA synthesis. Destroy erythroblasts and RBCs.
145
Q

Define hypochromia

A

Pale staining RBCs

146
Q

Define microcytic

A

Unusually small RBC

147
Q

What is the more severe form of thalassaemia?

A

beta

148
Q

What encodes for beta chains?

A

Single genes on chromosome 11

149
Q

What are the two types of mutations to beta chains?

A 
Betao = loss of beta chains
Beta+ = inadequate synthesis
150
Q

How does the body try and compensate for a beta thalassaemia?

A

Compensatory increase in HbF and sometimes HbA2

151
Q

What is the genotype of thalassaemia major?

A

betao/betao, beta+/beta+, betao/beta+

Severe anaemia

152
Q

What is the genotype of thalassaemia minor?

A

betao/beta, beta+/beta

Mild anaemia

153
Q

What is ineffective erythropoiesis?

A

Erythrocyte destruction

154
Q

What does ineffective erythropoiesis lead to?

A

Bone marrow expansion
Erosion of cortical bone e.g. skull
Extra-medullary haemopoiesis e.g. liver and spleen
Excessive absorption of dietary iron –> iron overload (effect on heart)

155
Q

What does iron deposition in the heart cause?

A

Deposits in bundle of His and purkinje fibres –> conduction defect
Congestive cardiomyopathy

156
Q

What encodes alpha globins?

A

Two duplicated genes on each chromosome 16 such that each contributes 25% of the total alpha globin protein

157
Q

What normally closes alpha thalassaemia?

A

deletion

158
Q

What decides whether alpha or beta thalassaemias are more severe?

A

Free beta and gamma chains are more soluble than free alpha chains - question of relative solubility of the unaffected chain

159
Q

What is the phenotype of each of the following genotypes:-alpha/alphaalpha

  • -/alphaalpha or -alpha/-alpha
  • -/-alpha
  • -/–
A

silent
Alpha thalassaemia trait (mild anaemia)
HbH beta4 disease (severe anaemia)
Hb barts (gamma4) disease (lethal in utero)

160
Q

Define hypoplastic anaemia

A

Anaemia due to reduced cellularity of marrow

161
Q

Define erythroblast

A

Nucleated early red cell precursor

162
Q

Define megaloblast

A

Abnormally large red cell precursor

163
Q

Define normoblast

A

Nucleated late red cell precursor

164
Q

Define spherocyte

A

Small spherical red cell

BOD MVST 1b (9 decks)

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