Blood Flashcards
(24 cards)
What are the main functions of blood?
1) Transport of oxygen and nutrients to the tissues
2) Transport of carbon dioxide and waste away from the tissue
3) Transport of hormones (long distance communication) and cytokines (short distance communication)
4) Immunity (contains leukocytes)
Distribution of homeostasis to the whole body:
5) pH balance
6) water balance
7) thermoregulation
What is haemostasis?
Blood clotting to stop blood loss in the site of injury.
What are the cells (formed elements) found in blood?
1) erythrocytes (red blood cells)
2) plateletes (thromocytes)
White blood cells (leukocytes):
3) lymphocytes
4) monocytes (differentiate into macrophages if needed)
5) neutrophils
6) eosinophils
7) basophils
What are the components of blood plasma?
- water (91-92%)
- ions (Na+, K+, Mg2+, Ca2+, Cl-, bicarbonate, phosphates, sulphates). Na+ and Cl- are the most abundant.
- amino acids
- albumins
- globulins (alpha, beta and gamma/antibodies)
- fibrinogen
- glucose
- lipids
- nitrogenous waste (urea, ammonia, uric acid, creatinine)
- oxygen
- carbon dioxide
- trace elements and vitamins
What are key blood plasma proteins?
1) albumins:
- produced by liver
- maintain osmotic (oncotic) pressure by drawing water away from tissues back to capillaries
- carriers of fatty acids, ions and billurubin and many external drugs
- most abundant blood plasma protein
2) globulins:
- alpha-1 globulins (inhibit immune proteases in lungs; transport of cholesterol, copper, retinol, progesterone and corticosteroids)
- alpha-2 globulins (haeme degradation, inhibits proteases, dissolves blood clots; copper, iron, fat, cortisol, vitD and thyroid hormone transport; angiotensinogen)
- beta globulins (transport of sex hormones, iron; dissolve blood clots; angiostatin; activation of complementary system)
- gamma globulins are antibodies produced by B cells
- fibrinogen: key clotting factor that is converted to fibrin, produced by liver
What are the features of erythrocytes?
- transport oxygen (oxyhaemoglobin) and carbon dioxide (carbaminohaemoglobin) between the lungs and body
- haemoglobin carries oxygen, tertramer globin protein, 4 haem groups (a porphyrin ring with iron atom in the centre)
- carbonic anhydrase to convert 70% of carbon dioxide into bicarbonate ions
- no nucleus to accommodate more harmoglobin and make them more flexible
- biconcave disks, 7.5 micrones in diameter
- 4 month life span (90-120 days), removed by macrophages in red pulp of spleen, liver and bone marrow
- erythropoiesis (erythrocyte production) is stimulated by hormone erythropoietin in red bone marrow
What are the features of thromocytes?
- take part in blood clotting
- much smaller that erythrocytes, hence no nucleus
- only contain secretary granules needed for clotting
- life 10 days
- 1 trillion plateletes in blood in adult person
- 1/3 is stored at red pulp of the spleen to be released at demand
- thrompopoeisis (platelet formation from megakariocytes):
1) thromboietin leads to megakariocytes maturation
2) megakariocytes undergo mitosis 7 times but no cytokinesis, forming huge polyploid cell
3) plateletes peel out from the edges of a megakariocyte
What are the 3 key mechanisms to minimise blood loss during injury?
1) Vasoconstriction
2) Formation of a sticky platelet plug
3) Surrounding plug with usoluble fibrin web and erythrocytes (coagulation). Granules from platelets convert soluble fibrinogen into unsoluble fibrin
What does normally prevent from blood clot formarion?
1) collagen (haemostasis activator) is separated from blood with undamaged endothelium
2) Endothelium secretes nitric oxide and prostaglandin (prostacyclin/PGl2) which perform vasodilation preventing plateletes from aggregating
3) enzyme CD39 breaks down ADP (platelet aggregation factor) to AMP.
How platelet plug is formed?
1) there are Willebrand’s factors (produced by endothelium) on collagen
2) when endothelium is damaged, collagen and Willebrand’s factors are exposed and thrombocytes bind tightly to them (even flow cannot remove them)
3) collagen activates thromocytes: they release ADP (activates release of the next chemical and changes shape of platelets so they become sticky to each other) and thromboxane A (vasocontriction to aggregate more platelets to the site).
What is an intrinsic pathway of coagulation?
1) protease called factor XII is activated after exposure to collagen negative charge under damaged endothelium
2) XII activates XI
3) XI activates IX
4) Formation of VIII complex from VIII, IX, calcium and phospolipids
5) VIII compex activates X
6) Formation of V complex from V, X, calcium and phospolipids
7) V complex activates conversion of prothrombin into thrombin
8) thrombin converts fibrinogen into fibrin
9) fibrin polymer sticks to platelets and traps erythrocytes inside to make a bigger gelatinous plug.
What is an extrinsic pathway of coagulation?
This is a quicker way to produce blood clot before endothelium damage.
1) normal damaged tissue releases thromboplastin (not present in blood)
2) thromboplastin activates VII
3) Formation of VII complex from VII, thromboplastin, calcium and phospolipids
4) VII complex activates X
The rest is same as intrinsic pathway:
5) Formation of V complex from V, X, calcium and phospolipids)
6) V complex converts prothrombin into thrombin
7) thrombin converts fibrinogen into fibrin
9) fibrin polymer sticks to platelets and traps erythrocytes inside to make a bigger gelatinous
What are anticlotting drugs?
- prescribed when patient may develop too many small clots which can obstruct blood vessels in brain, heart and lungs
- t-Pa (recombinant tissue plasminogen activator) like alteplase to convert plasminogen to plasmin which rapidly dissolves clots. Very useful during coronary artery caused heart attacks and ishemic stroke within 3 hours.
- heparin activates antithrombin III, which deactivates thrombin
- warfarin (coumarin) inhibits production of clotting factors II, VII, IX and X (like in case with Vitamin K) by competitively inhibiting vitamin K epoxide reductase complex 1. Common blood thinner, used against embolism.
- aspirin: inhibits prostglandin production, resulting in defective platelete release.
Why blood often coagulates in a simple glass vessel and how this is prevented?
Glass, like collagen, in negatively charged, which activates intrinsic coagulation pathway.
Sodium citrate or EDTA chelate calcium ion to prevent formation of V and VIII complexes and interrupt intrinsic coagulation pathways.
What is fibrinolysis?
Dissolving a clot, usually with drugs.
What are the 3 key classes of blood disorders?
1) coagulation disorders
- haemophilia A
- hemophilia B
- thrombocytopenia (too little plateletes)
- Von Willebrand
2) leukocyte disorders:
- leukopenia: deficiency, especially of neutrophils (increased risk of infection)
- leukocytosis: excess (increased risk for inflammation, often happens after chronic infections)
- leukemias (myeoloma and lymphoma): cancer, malignant tumors of precursors in bone marrow, ending up in extremely high WBC count
3) anemias
What is the difference between hemophilia A and B?
Both are genetic and inherited (X-linked and recessive).
Both are defects in clot formation which leads to excessive bleeding even after small injuries or bruises (delayed formation of fibrin)
Haemophilia A:
- absent subunit at clotting factor VIII, leading to activated factor VIII deficiency
- 80% of haemophilia cases
Haemophilia B (Christmas disease):
- defective clotting factor IX
What is Von Willebrand’s disease?
- deficiency of Von Willebrand’s factors on collagen, so prevents platelet plug formation
- defective and deficient VIII
- autosomal dominant
What is role of vitamin K in blood clotting?
To produce clotting factors II, VII, IX and X.
Lack of Vitamin K leads to hemmorage (symptoms similar to haemophilia).
E. Coli in large intestine also produces Vitamin K.
What is embolism?
Clot obstruction of an artery.
What are the differences between acute and chronic leukemia?
Acute:
- from less mature cells
- abnormal differentiation
- develops quickly
- symptoms appear quickly
- needs urgent medical intervention
- mostly in children
Chronic:
- develops slowly, takes years to see the symptoms
- from more mature cells
- no abnormal differentiation
- mostly in adults
What are the types of anemia?
1) Aplastic: bone marrow defect or arsenic or radioactive toxicity
2) Iron deficiency: Low intake or significant blood loss. Erythrocytes often appear partially colorless after staining
3) sicke cell anemia: beta chain single nucleotide mutation in haemoglobin, results in abnormal crescent shape of erythrocytes
4) haemolytic (hereditary spherocytosis): defective cytoskeleton leads to many erythrocyte bursting from osmotic pressure (haemolysis)
5) pernicious: autoimmune attack of intrinsic factors; intinsic factor deficiency leads to intestinal malsorbtion of Vitamin B12
What is the role of B12 at healthy erythrocyte formation?
- Acts as a growth factor alongside erythropoietin
- synthesis of pyrimidine bases to make sure cell cycle in erythrocytes precursors goes correctly (so no nucleated erythrocytes are formed)
What are the features of sicke cell anemia?
- overrepresented in blacks (8-11% of the Afro-Americans)
1) A –> T mutation leads to glutamic acid –> valine amino acid substitutution at beta-globin, position 6
2) Results in haemoglobin S form
3) haemoglobins S crosslink with each other to form polymerased fibres leading to insoluble paracrystalline gel
4) it makes erythrocytes collapse to sickle shape in the lack of oxygen
5) those RBCs are less flexible and more fragile, they cannot easily pass through capillaries, slowing down transport
6) sickle cells can aggregate on exch other and block capillaries, causing ischaemia (and hence pain crisis) and inflammation in chest, abdomen and joints.
7) Poor oxygen delivery leads to damage in brain, eyes, liver, heart, lungs, spleen and kidneys.
8) Sickle cells have much shorter life span: 10-20 days
