Clotting

Question 1

blood

Answer 1

complex fluid, centrifuge to separate
RBC go to bottom
thin layer of WBC and platelets
top section is cell free plasma

Question 2

hermatocrit %

Answer 2

= amount of RBC

height of RBC / height of tube

Question 3

extracellular fluid

Answer 3

plasma

very rich in proteins

Question 4

erythrocytes

Answer 4

RBC
most abundant elements
non nucleated bi concave disc - max SA:vol
shape maintained by cytoskeleton anchored to plasma membrane by: glycophorin, band 3 Cl/HCO3 exchanger
3 major functions:
O2 carriage from lungs into systemic system
CO2 carriage from tissues to lungs
buffering of acids/bases

Question 5

leukocytes

Answer 5

WBC
can be granulocytes:
neutrophils - phagocytose bacteria
eosinophils - combat parasites and viruses
basophils - release IL-4, histamine, heparin and peroxidase
non granular: lymphocytes
T cell - cellular immunity
B cell - humoral immunity 
monocytes:
macrophages and dendritic

Question 6

plasma

Answer 6

watery solution of electrolytes, plasma proteins, carbs and lipids
run electrophoresis –> principle proteins = albumin, fibrinogen, globulins and other coagulation factors

Question 7

platelets

Answer 7

bud off from megakaryocytic in bone marrow (TPO-thrombopoietin and IL-3 intaleukin, dependant)
feedback mechanism -
platelet receptor for TPO - abundant platelets bind to TPO - TPO now not available for megakaryocytes - plaelets cant be made - no TPO receptors - TPO stimulates megakaryocyte production - platelets generated

nucleus free fragments
contain mitochondria, lysosomes, peroxisomes, alpha granules and dense core granules
external coat rich in platelet receptors
inner skeleton - circumferential band of tubulin microtubules

Question 8

alpha granules

Answer 8

contain von willibrands factor, platelet fibrinogen and clotting factor 5

Question 9

dense core granules

Answer 9

contain:
ATP/ADP
seratonin
Ca

Question 10

blood flow - viscosity

Answer 10

increase in hermatocrit = inc viscosity
viscosity = resistance to sliding of shearing fluid layers, dependant on:
hematocrit (normal = 35-50%)
fibrinogen plamsa conc
vessel radius
linear velocity
temperature

Question 11

velocity of blood flow

Answer 11

in a cylinder vessel, laminae of blood are cone shaped, each layers flow gets faster as it gets closer to the center of the vessel
central = much faster than outer layer
lower viscosity = sharper point
RBC con = greater in middle

Question 12

small vessels

Answer 12

axial accumulation of cells leads to plasma skimming in branch vessels (lower hematocrit)
skimming prevention by arterial cushion, lamina layers are limited to width of RBC, limiting numbers in small vessels
in small capillaries RBC membrane rolls around cytoplasm ‘tank treading’ - 2 adjacent cells spin plasma
vessels smaller than RBC derform the cell and viscosity falls

Question 13

turbulence

Answer 13

at high flow rate (above critical velocity) blood flow in no longer laminar = turbulence
parabolic profile of velocity is blunted
turbulent flow occurs when:
radius is large e.g. aorta
velocity is high e.g. cardiac output
local stenosis - restriction = inc velocity
clinical significance = laminar flow is silent, turbulent flow murmurs

Question 14

haemostasis

Answer 14

prvention of haemorrhage through:
vasoconstriction - thromboxane A, seratonin, thrombin, endothelin-1
increase tissue pressure and decrease of transmural pressure (difference between intravascular and tissue pressure)
platelet plug - small breaches in vascular endothelium through - adhesion of platelet, activation and aggregation
coagulation/clot formation - semisolid mass of platelets and fibrin mesh with trapped RBC, WBC and serum
injury/damage —-> vessel contracts —–> platelet plug

Question 15

platelet adhesion

Answer 15

mediated by platelet receptors to bound ligands, endotehlial cells von willibrand factor release triggered by: high shear forces, cytokines and hypoxia
breach of endothelium exposes: collagen, fibronectin and laminin
activation - ligand binding leads to conformational change in receptors —-> intracell signalling cascade initiated —-> release reaction/exocytosis of dense storage granules and alpha granules
intracell signalling cascade also leads to cytoskeletal changes in lamellipodium
aggregation - activation leads to conformational change in receptor, allows it to binds to fibrinogen - forming molecular bridges between platelets

Question 16

blood clot

Answer 16

semi solid mass: erythrocytes, leukocytes, serum, mesh of fibrin and platelets
activating events trigger chain reaction converting precursors into activated factors, controlled proteolysis amplifies clotting signals
thrombus = intravascular clot, can form in pathological situations
CVS - balance between states of inadequate clotting ( extensive haemorrhaging and blood loss) and overadequate clotting
DVT risk factors - venous stasis, vascular injury, hypercoagubility
arterial thrombosis - following erosion or rupture of atherosclerotic plaque

Question 17

clotting intrinsic pathway

Answer 17

surface contact activation

on membrane of activate platelets

Question 18

clotting extrinsic pathway

Answer 18

membrane bound tissue factor activation
activated when blood contacts material from damaged cell membranes

both end in common pathway that generates thrombin and stable fibrin

Question 19

blood clot prevention

Answer 19

homeostatic mechanisms prevent haemostasis
endothelial cells maintain normal blood fluidity through:
paracrine factors e.g. prostocycline - promotes vasodilation, inc blood flow, dec clotting e.g. nitric oxide - inhibits platelet adhesion and aggregation
anticoagulant factors e.g. TFP1 on endothelium cells - maintain anti thrombotic surface, prevents cascade