Blood + Haemostasis\ Flashcards
What is blood?
Circulating tissue composed of fluid plasma and cells. Anatomically considered CT
Bright red in art, dark red in veins, 4-5 more viscou than water
Vol -
5-7L in M and 4-5 L F
Distrib - art (14.6%), cap (5.4%), V (66%)
Function - Transport, Regulation, Homeostatic, Defensive
Composed of 2 parts
Plasma (55%)
Formed cellular elements (45%) - RBC (4-6x10^12/l), WBC (5-10x10^6/l), platelets (150-300x10^9/l)
Ht - ratio of vol RBC to total blood vol
(norm 0.4-0.55 l/l M (40-55%), F 0.35-0.5 l/l (35-50%))
Plasma
90% water, 7-8% sol proteins (imp for osmotic pressure), 1% CO2, 1% elements in transit, 1& salt
Carry resp gases (co2,o2), nutrients, wastes, hormones, vitamins etc.
Plasma proteins
Albumin (58-60%, 32-53g/l) - plasma protein, help maintain colloid osmotic pressure (stop plasma loss), transport diff material e.g. vita, molecules, drugs e.g. FA, bilirubin. Lower Mr and strongly charges
Globulin (35-38%) - gamma, alpha, beta. Transport substances in blood. Enzymatic fct, Gamma assist immunity (highest Mr + weakly charged)
Clotting Proteins (2-4%) - mainly produced in liver. FIBRINOGEN - imp blood clot formation (fibrin threads)
Formation - mainly produced in liver (50-80%) rest in lymphoid organs
Can be source of AA in tissue
Blood serum 0 plasma - fibrinogen
Plasma colloid pressure = 28mmHg
Plasma osmotic pressure = 290 mOsm/L
Where are plasma proteins formed
mainly produced in liver (50-80%) rest in lymphoid organs
What are the 3 groups of plasma proteins
Albumin (58-60%, 32-53g/l) - plasma protein, help maintain colloid osmotic pressure (stop plasma loss), transport diff material e.g. vita, molecules, drugs e.g. FA, bilirubin. Lower Mr and strongly charges
Globulin (35-38%) - gamma, alpha, beta. Transport substances in blood. Enzymatic fct, Gamma assist immunity (highest Mr + weakly charged)
Clotting Proteins (2-4%) - mainly produced in liver. FIBRINOGEN - imp blood clot formation (fibrin threads)
Iron metabolism
Fct - o2 transport + storage, elctron transport, enzymes, cell cycle control
Total body iron around 4-5g (65% in Hb, 4% myoglobin, 1% heme compounds promoting intracellular oxidation, 01% transferring, remainder is stored (esp reticuloendothelial system = liver parenchyma mainly as ferritin)
1) Iron absorbed in smI mainly (Fe3+> reduced to Fe2+) > absorbed by DMT1 > can be stored as ferritin or effluxed by ferroportin >
2) combine w/ apotransferrin (beta globulin)> transferrin which can transport in plasma > can be released. 3) In cell iron combines w/ apoferritin > ferritin (storage)
Sm amount stored as hemosiderin (insoluble)
If plasma iron decrease > ferritin > transferrin > ingested via endocytosis into erythroblasts
Regulation via hepcidin
RBC
Biconcave disc, 7.8um D x 2.5 um, no nucleus, mitochondria, other organelles, generate ATP anaerobic glycolysis. Plasma membrane (glycolipid+proteins, perm to h20, anions, NH3, urea, aldehydes and alcohols). Structural (spectrin, ankyrin, actin, tropmyosin, tropomodulin)
120 days life cycle
M - 4.5-5.5 x10^12/L F - 4-5x10^12
- polycythaemiz (age - more at birth, sex, high altitude, exercise)
- oligocythaemia (alimentary erythropenia)
MCV - M 87 +/- 2fl, F 87 +/-5 fl [average RBC vol]
MCH - 29 +/- 2.5pg [average mass Hb per RBC]
MCHC - M 320 +/- 25g/l F 340 +/-2-g/l [measure of concentration of Hb per vol RBC)
Fct
Transport Hb
Acid base buffer
carbonic anhydrase (co2 + h20> h2co3 > H+ + hco3-)
Glycolysis ^ 2,3-DPG > decrease affinity of Hb to o2 > release
Hb - 4 subunits
HbA1, HbA2, HbS, HbF
tetrapyloric haem w/ Fe2+ which binds oxygen
OxyHb - bind loose + reversible w/ o2 (coordination bond), removal w/ increased pH, 2,3 DPG, pCO2, temp
CarbaminoHb - co2 + Hb
Carboxy Hb - CO + Hb (increased affinity x200, reduced o2 carrying capacity. headache, convulsions, nausea)
Methemoglobin - Fe3+ instead of Fe2+, cannot remove o2
HCT - ratio of RBC vol:total blood vol
change w/ no. RBC, plasma vol, RBC vol
RBC production
Early embryonic - yolk sac > liver, spleen, lymph nodes
Last gestation - red BM until 5yr (become more restricted to axial skeleton esp ilia, sternum vertebrae)
EPO (glycoprotein) - produced by peritubular interstial cell of kidney (90%), and liver (10%)
1) mainly stim by hypoxia > stim HSC > proerythroblast
2) >early erythroblast > late erythroblast > normoblast >
3) reticuloculocyte >RBC > INCREASE TISSUE OXYGEN
* Hb synth from proerythroblast > reticulocyte ( heme binf globin > haemoglobin)
* Vit B12 + folic acid important for synthesis of DNA and mature. Deficiency > megaloblastic anaemia
* Fe2+ req, lack > microcytic anaemia
Destruction
Old RBC > macrophages in spleen liver and BM > broken into Fe2+, AA, Heme
Heme -> biliverdin > bilirubin in macrophae -> liver > excreted as bile in kidneys as urine or in feces
ESR
Rate which rbc sediments when blood containing anti-coag is allowed to stand in vertical rube (mm/h)
Factors that affect ESR:
• Rouleaux formation – RBCs sediment faster because they stack on top of each other. Bacterial proteins and products of inflammation increase rouleaux formation.
• Number of RBCs – decrease in RBCs increases ESR.
• Size of RBC – increase > ESR increases.
• Viscosity of blood – increased > ESR decrease
Increase in ESR can be
Physiological (Due to pregnancy, menstruation and sex i.e. higher in F, increased temp)
Pathological (acute infection, chronic infection and anaemia, malignancy)
Methods for ESR determination:
• Panchenkov’s method
Uses a Panchenkov’s pipette which is calibrated from 0-100 and is 150mm long.
25mm of Na citrate 5% is mixed with 100mm of blood and the results are read after the 1st hour. Normal values for males is 12mm and females is 15mm.
• Westergren’s method
0.4ml of sodium citrate is drawn into a 2ml syringe and mixed with blood from cubital vein.
The mixture is emptied into the tube (calibrated from 0-200 and 300mm long) and the tube is left to stand. Results are read after 1st hour and after 2nd hour.
Normal value: M 3-8mm in 1st hour, 9-15mm after 2 H; F after 1st hour is 5-9mm and 10-18mm
WBC
Formed in BM (granulocytes and monocytes) and partially in lymph tissue (lymphocytes and plasma cells)
5-10x10^6l
Graulocytes - Lifespan normally 2-8h in blood, 4-5 days in tissue
Neutrophils - 55-60%, 10-12um, 2+ nucleur lobes connected by narrow strands, actively mobile, phagocytic, primary immunity
- specific granules (enzymes)
- azurophillic granules (lysosomes w/ BPI protein, hyrdolases, cathepsin G, collagenase, elastase, lysozyme, myeloperoxidases, )
- tertiary ( gelatinase, cathepsins, glycoproteins)
-chemotaxis > diapedesis > transendothelial migration> phagocytosis as it bind to receptor
- Main regs - cytokines
stimulation via (IL-1,6,8), TNFa, IFNy, hemopoietic factors, inhib via IL4,10
Eosinophils - 1-3%, 10-12um, bi-lobulated, coarse pink granules (crystalloid body), excrete cytotoxic substances
- motile, chemotaxis, weak phagocytes in mucus memb of intestine, lungs, dermis, increases in parasitic infections
- prominent in allergic reaction
- attracted by eosinophillic chemotactic factor (mast, basophils)
Basophils - 0.5-1%, 10-12um, irreg nucleus, not lob,
- dark stain granules - heparin (prevent blood coag) and histamine can gen leukotrienes > slow contraction of sm muscl
- motile, supplement mast cells
- also secrete bradykinin and serotonin
- imp allergy, IgE easily bind
Agranulocytes
Monocytes - 3-7%, 15-20um, ovoid nucleus, often indented, abundant cytoplasm
- azurophillic granules - lysosome
- actively motile. when eave blood > tissue > macrophages
- phagocytosis, process and intro antigen to lymphocytes, cytokine secretion
- relate primary and acquired immunity
Lymphocytes - 25-33%, size vary, intesly staining round nuclei, thin rim of cytoplasm
- actively motile
- T lymph - form in BM > thymus
- B lymph - formed in BM , can differentiate into plasma cell > Ig
Macrophage and Neutrophil response in tissue inflam
1) macrophage
2) neutrophi; > neutrophilia
3) 2nd macrophage inavsion
4) increase granulocyte production in BM
What is Hemostasis
Prevention of blood loss
1) vasc constriction
2) formation of platlet plug
3) blood clot formatio
4) eventual growth of fibrous tissue
*See sheet
Platelet
Minute disc 2-4um D, 150-300x10^9/l
Formed in BM from megakaryocytes, no nuclei
Cytoplasm - contractile proteins, skeleton, mitochondria, granules, enzymes
Dense granules - mediators of platlet activation e.g. serotonin, ADP, catecholamines, Ca2+
Alpha granules - F V, VIII, fibrinogen, vWf, platlet factor 4, platlet derived growth factor
Glycogen granules - energy source
Blood groups
Type A - antigen (agglutinogen) A, B antibodies (anti B agglutinins)
Type B - antigen B, A antibodies
Type AB - antigen A + B, but no antiodies to o
Type O - no A or B antigen but AB antibodies
Allels
Rhesus grouping - C, D E but D most antigenic
no natural Rh antibody produced until 1st exposure, cannot cross placental barrier but may come in contact during deliver
Heamolytic disease of newborn - > agglutination of fetal blood > Hb release > converted into bilirubin > jaundice > hypoxia and kenicterus. Treat w/ phototherapy (expose infant w/ UV light to degrade bilirubin) mother should also be treated with RhoGam
Important in organ and blood donation and in pregnancy
acute kidney failure and jaundice can occur from mismatched transfusion
Autograft - same person
Allograft - different person
Isograft - identical twin
HLA - most imp for graft rejection, more than 150 HLA antigens and only 6 antigens present on WBC - closest match best
graft rejection prevention - glucocorticoid, drugs toxic to lymphoid,
-cyclosporine - inhib T-help formation
Resistance of the body to infection
Immunity - ability of body to resist infection
Acquired - develop after 1st attacked, specific
Innate - primary non specific response
1) skin and barrier
2) Drainage and irrigations, chemical protection, normal bacterial flora
3) phagocytosis by WBC
4) destruction of swalled organism via secretion of stomach and digestive enzymes
5) Presence of chemical than attach to foreign organism/ toxins and destroy them
Innate
