ic2 - rbc, platelets and hemostasis Flashcards
what are the components of blood and its proportions
plasma (55%), buffy coat (<1%), erythrocytes (45%)
plasma contains water (92%) and proteins (7%) and solutes (<1%)
buffy coat contains WBC and platelets
erythrocytes contains RBC
what are the proteins and its functions in our blood
albumin carries proteins that are lipid soluble and important in maintaining osmotic pressure, globulins important for immune function and clotting, fibrinogen is an inactive protein that needs to be activated into fibrin for clotting
where are proteins made
in our liver
what are the solutes
ions, nutrients, gases and waste
list the types of wbc in order of most to least abundant
neutrophils, leukocytes, monocytes, eosinophils, basophils
what is the function of wbc
important for immune defense
what are platelets and its function and another name for platelets
platelets are also known as thrombocytes and are fragments of cells produced in the bone marrow that play an important role in clotting and protection of vascular system
what is the function of rbc
transport of gases and to buffer the blood pH
what is the pH of blood
7.35-7.45
what is the weight of blood
8%
what is the volume of blood in males and females
males 5-6L, females 4-5L
what is the temperature of blood
38degC
what type of tissue is blood
connective tissue
what colour is blood
bright red if O2 rich from the artery, dark red if O2 poor from the vein
compare the structure of wbc, rbc and platelets
wbc are complete cells, rbc have no nuclei or organells, platelets are cell fragments
do rbc cell divide
no they are renewed by cells in bone marrow
what is the three main function of blood
transportation, regulation, protection
what does it mean to measure hematocrit and what is the average value for male and female
measuring rbc% of whole blood (46 for men, 42 for women)
what does hemoglobin consist and what are they
hemoglobin consist of heme and globin
globin is 4 folded polypeptide chains (2 alpha 2 beta) whose AA sequence determine affinity to O2 and each chain binds 1 heme group
heme is not a protein but a pigment and each heme group contains 1Fe which can bind to 1 O2 molecule (weak and reversible binding)
how many O2 can one Hb transport
4
what are the types of Hb
oxyhemoglobin, deoxyhemoglobin, carbaminohemoglobin
distinguish between pulmonary circuit (pulmonary arteries and pulmonary veins) VS systemic circuit (systemic arteries and systemic veins)
pulmonary circulation moves blood from heart to lungs while systemic circulation moves blood from heart to rest of body
artery vs vein differ in terms of direction (as long as from heart it is artery vs to the heart is vein)
pulmonary artery vs systemic artery differ in terms of gas content (pulmonary artery is O2 poor vs systemic artery is O2 rich)
which circulation has higher pressure
systemic circulation
what is erythropoiesis
generation of erythrocytes controlled by erythropoietin
where does erythropoiesis occur
for fetus, yolk sac then liver, spleen and lymph node
for <5yo, all bone marrow
5-20yo, bone marrow in ribs, sternum, vertebrae and proximal ends of long bones
> 20yo, bone marrow in ribs, sternum and vertebrae
where is erythropoietin produced
kidney
what happens when there is decreased O2 delivery to kidney and other tissues
cells in kidneys release more erythropoietin which increases rate of erythropoiesis and once O2 delivery is sufficient, the kidneys will decrease output of erythropoietin
what is the measurement that is indicative of erythropoiesis and what is the normal range of that measurement
reticulocyte count, normal range 0.8-1%
what are hematopoietic stem cells
immature cell that can develop into all types of blood cells incl wbc, rbc and platelets
explain the step by step process of erythropoiesis
hematopoietic stem cells in bone marrow give rise to proerythroblasts
proerythroblasts develop into erythroblasts in three phases: ribosome synthesis in early erythroblasts, Hb accumulation in late erythroblasts and normoblasts, ejection of nucleus from normoblasts and formation of reticulocytes which are preRBC
reticulocytes continue Hb synthesis and leave the bone marrow and complete differentiation into mature erythrocytes in blood
old RBC self destructs as the lack of protein synthesis makes membranes fragile and Hb degrades
they become ruptured in tiny vessels of spleen and these dying RBC and components are taken up by macrophages (in liver and bone marrow also)
what does the heme and globin give upon destruction of rbc
from heme, the Fe binds to transferrin and is recycled and reused in bone marrow or stored in liver
from heme, heme can also degrade into yellow pigment bilirubin which is excreted via liver and bile into urine and feces
from globin, it metabolises into AA and released into circulation
what is the lifespan of a rbc
100-120 days
how long does erythropoiesis take
about 7days
what triggers erythropoietin release by the kidneys
hypoxia due to decr RBC number or function, decreased O2 availability, increased tissue demand for O2, anemia, reduced blood flow to kidney, blood donation
is erythropoietin enhanced be androgen or estrogen
androgen thus men have higher RBC concentration than women
what condition does elevated hematocrit suggest and what condition does depressed hematocrit suggest
elevated suggests polycythemia while depressed suggests anemia
what condition does elevated reticulocyte count suggest and what condition does depressed reticulocyte count suggest
elevated suggest reticulocytosis while depressed suggests defect erythropoiesis
what condition does elevated rbc count suggests and what condition does depressed rbc count suggest
elevated suggest erythrocytosis or polycythemia while depressed suggests anemia
what does depressed Hb suggests
anemia
what is mean corpuscular volume (MCV)
average volume or size of RBC
what is mean corpuscular hemoglobin (MCH)
average amount of Hb in RBC
what is mean corpuscular hemoglobin concentration (MCHC)
average conc of Hb in RBC (amount/vol)
what is red cell distribution width (RCW)
how RBC size varies
what does elevated RCW suggest
anisocytosis (may be an early indicator of anemia)
what is anemia
reduction below the normal capacity of the blood to carry O2 due to reduction of erythrocyte numbers and/or reduction in Hb function
what determines viscosity of the blood
RBC conc in blood
what happens to O2 distribution into tissues when there is reduction in RBC
RBC reduction causes blood to become very liquid and if blood rushes too fast through the tissues they release too little O2 thus causing hypoxia which will widen blood vessels and eventually effect is reinforced and the widening of vessels and blood rushing greatly increases the workload for the heart and may potentially result in cardiac arrest
what are the sx of anemia
fatigue, paleness, sob, chills
what are the types of anemia
nutritional - caused by dietary deficiencies
aplastic - failure of bone marrow to make sufficient RBC (maybe due to chemotx)
renal - due to kidney disease resulting in lack of erythropoietin
hemorrhagic - loss of significant amounts of blood
malaria - plasmodium falciparum amplifies in RBC thus rupturing them and offspring invades new RBC
sickle cell - mutation in beta-globin gene causing Hb to aggregate in low O2 conditions to crescents which rupture RBC membranes
erythroblastosis fetalis - Rh+ RBC of fetus destroyed by anti-Rh Ab of a Rh-mother
thalessemia - low production of Hb (hereditary in nature)
what is pernicious anemia
refers to lack of vitB12 or intrinsic factor
what is Rh and why might it be dangerous in pregnancy and is it first pregnancy
Rh is a protein that can be found on surface of RBC (if you are Rh+ means it is present)
dangerous only in second or later pregnancies if the anti-Rh Ab in a mother of Rh negative passes into Rh positive baby as the Ab will then attack Rh positive RBC in the baby
what is polycythemia/ erythremia
excess in circulating erythrocytes, causing elevated hematocrit
what can polycythemia cause
polycythemia causes very viscous blood and potentially plugging of capilarries resulting in insufficient O2 delivery to tissues
what are the types of polycythemia
primary - tumor or tumor like condition in bone marrow
secondary - erythropoietin induced, adaptive mechanism to improve O2 carrying capacity of blood
others - dehydration
what is the range of RBC count that differentiates primary and secondary polycythemia
primary has 7-8x10^9 RBC/mL while secondary has 6-7x10^9 RBC/ml
what are the types of disorders related to leukocytes
leukopenia - too few leukocytes (includes lymphopenia, neutropenia etc)
leukocytosis - elevated wbc count
leukemia/ lymphoma - cancers of wbc
what does leukopenia pose as a risk to and what is it caused by
leukopenia increases risk of opportunistic infections and can be caused by chemo tx, radiation, chemicals, viral infections
what is the likely wbc count indicative of leukocytosis and what is it caused by
> 1.1x10^7 wbc/ml and is a normal response to bacterial or viral invasion, may indicate cancer of wbc
what is the likely wbc count indicative of leukemia/ lymphoma
up to 5x10^8 wbc/ ml (normal count is 4-11 x10^6 wbc/ml)
what can leukemia/ lymphoma cause and what are its tx options
can cause immune deficiency and many infections, anemia and hemorrhage as bone marrow can become completely occupied by cancerous leukocytes and the wbc produced are not functional and will displace the remaining healthy ones
tx include irradiation, chemotx and bone marrow transplantation
what is hemostasis
natural reaction to an injury whereby there are processes aimed at closing a leak in the vascular system with an aim to prevent loss of blood
how long does clot retraction take and what is it mediated by
20mins to an hr and is mediated by platelets
after a few hrs, clot is dissolved or is invaded by fibroblasts
what are fibroblasts
type of cell that contributes to the formation of connective tissue
how long does healing take
1-2w whereby fibrous tissues replaces blood clot
what are the three main phases part of hemostasis
vasoconstriction, formation of platelet plug and fibrin clot
explain what happens during vasoconstriction as part of the
damage to blood vessel wall causes constriction of smooth muscle to limit the amount of blood going through thus limiting the amount of blood that may be left from the damage in the wall –> reduces blood loss but most of the times insufficient
immediate and lasts for approx 30mins or maybe hrs
indicated by sympathetic nerves and mediated by vascular smooth muscle cells
correlates with damage and provides time for platelet and coagulation phase
endothelial cells of opposite sides may stick together, and contract which exposes basal lamina
explain what happens during platelet plug formation
damage to blood vessel wall causes collagen fibers to be exposed which serve as little flags to platelets moving through the blood vessel
platelets will recognise and adhere to collagen mediated by von willebrand’s factor (vWF) which is a plasma protein produced by platelets
adhesion activates morphological changes in platelets which triggers the release of granules that contain platelet agonists such as ADP and TXA2
TXA2 promotes aggregation and further vasoconstriction, fibrinogen links platelets through glycoprotein receptors but links are weak thus need reinforcement from factor XIII
platelet aggregation also releases prothrombin activator which activates prothrombin into thrombin
as more platelets stick together, platelet plug is form and results in a positive feedback cascade
occurs within seconds
where is prothrombin produced and what does it require
prothrombin is produced in the liver and requires vitK
what is thrombin and what is its function
thrombin is a molecular scissors that cuts protein fibrinogen into fibrin and activates factor XIII into XIIIa which is the fibrin stabilising factor, and along with fibrin, forms fibrin mesh
what are the main functions of the platelet plug formation
closure of leak by formation of temporary patch, release of chemical mediators to regulate blood clotting and contraction of blood clot
how do intact endothelial cells prevent unintentional platelet activation and aggregation
intact endothelial cells release No and prostacyclins that inhibits unintentional platelet activation and aggregation
explain what happens during the coagulation phase
platelets and fibrin are present at site of damage and reinforces the clot, remodelling occurs after this to fix the damaged wall by fitting in connective tissues
occurs within mins
what happens in secondary hemostasis
coagulation cascade and formation of final stable fibrin clot
platelets arriving at site of injury and the coagulation cascade is activated along with various coagulation factors which involves the intrinsic, extrinsic and common pathway
where does extrinsic path take place and explain what happens in the extrinsic path
extrinsic path is when tissue damage occurs outside the blood circulation
damaged tissue releases tissue factor/ thromboplastin which converts factor VII to VIIa through formation of a complex and the presence of Ca2+ will activate factor X into Xa then Xa with Ca2+ and Va will activate prothrombin into thrombin
thrombin either activates fibrinogen into fibrin then form fibrin meshwork with factor XIIa or directly forms fibrin meshwork with factor XIIa
explain what happens in the intrinsic path
exposure to collagen fibers or exposure to foreign surface causes conformational change in platelet phospholipids leading to activation of factor XII into XIIa then XIIa activates XI into XIa then XIa in presence of Ca2+ activates factor IX into IXa and IXa in presence of Ca2+ and VIIa activates X into Xa then Xa with Ca2+ and Va will activate prothrombin to thrombin
explain what happens in the intrinsic path
exposure to collagen fibers or exposure to foreign surface causes conformational change in platelet phospholipids leading to activation of factor XII into XIIa then XIIa activates XI into XIa then XIa in presence of Ca2+ activates factor IX into IXa and IXa in presence of Ca2+ and VIIa activates X into Xa then Xa with Ca2+ and Va will activate prothrombin to thrombin
explain what happens in the intrinsic path
exposure to collagen fibers or exposure to foreign surface causes conformational change in platelet phospholipids leading to activation of factor XII into XIIa then XIIa activates XI into XIa then XIa in presence of Ca2+ activates factor IX into IXa and IXa in presence of Ca2+ and VIIa activates X into Xa then Xa with Ca2+ and Va will activate prothrombin to thrombin ……..
is extrinsic or intrinsic path faster
extrinsic bc intrinsic has alot of enzymes and enzymatic reactions involved
which is the point where extrinsic path meets intrinsic path
factor Xa
what does large amounts of thrombin cause
it causes further activation of platelets and the enhanced formation of fibrin
fibrin then form strands which makes up the mesh that stabilises the platelet plug in an arterial clot and holds together rbc in a venous clot
what are the factors involved in extrinsic path
VII, X, II (thrombin), I (fibrinogen), Va, XIIIa, IV (Ca2+)
what are the factors involved in intrinsic path
XII, XI, IX, X, II (thrombin), I (fibrinogen), Va, XIIIa, IV (Ca2+)
what are platelets
fragments of megakaryotes that are bone marrow boned wbc
what is the life span of platelets
5-7days
what do platelets have
contractile proteins actin and myosin that allows them to move
organelles like mitochondria for release of ADP and ER, and golgi for storage of Ca2+ and synthesis of enzymes
enzyme systems for synthesis of PG
growth factors PDGF and VEGF
factor XIII (fibrin stabilising factor)
what is the function of thrombin
key regulator of hemostasis
activator of XIII and platelets
release of PF3 from platelets to activate intrinsic path
enhances own generation (positive feedback loop)
which are the clotting factors produced in the liver and which clotting factors requires vitK
produced in liver: I, II, V, VII, IX, X, XI, XII, XIII
requires vitK: II, VII, IX, X
what is clot retraction and why does it occur
clot retraction is the stabilisation of clot by squeezing serum from the fibrin clot which serves to give further closure to the leak
how does clot repair occur
through stimulation of vascular smooth muscle cells by platelet derived growth factor (PDGF) to build new vessel wall and the stimulation of endothelial cells by vascular endothelial growth factor (VEGF) to multiply and restore inner endothelial lining
how is blood clotting regulated normally
prostaglandin produced by intact endothelial cells inhibits platelet activation and thus limits the spread of blood clotting
at high concentrations, serotonin inhibits ADP activity thus helping to regulate blood clotting
differentiate pro and anticoagulants
procoagulants are tissue factors, collagen while anticoagulants can come in the form of artificial (citrate, EDTA, VKA, DOAC) or endogenous (smoothness of endothelial surface, antithrombin III, heparin, thrombomodulin, tissue plasminogen activator tPA)
what is meant by the term fibrinolysis
dissolution of clots
explain the process of fibrinolysis
during clot formation, plasminogen (plasma protein and protease precursor made by liver) is trapped inside the clot
surrounding tissue and vascular endothelial cells slowly release tissue plasminogen activator (tPA) which cleaves the inactive plasminogen into protease plasmin
plasmin digests the fibrin thus dissolving the clot and macrophages remove the remains of the clot
does fibrinolysis occur constantly
yes it does at low levels and is balanced by equilibrium of thrombin and plasmin
what are the types of blood clotting disorders
hemophilia - in men, excessive bleeding after an injury, hereditary and caused by lack of clotting factors (hemophilia A is deficiency of VIII and is more common while hemophilia B is deficiency of IX while hemophilia C is deficiency of XI)
liver disease - inability to synthesise procoagulants as most clotting factors are produced by the liver and cannot produce bile to absorb fat and vitK
vitK deficiency - essential for synthesis of several clotting factors, half comes from gut half from diet
thrombocytopenia - low circulating platelet count (<50million/ml)
thrombosis - inappropriate clotting caused by roughened surface of vessel, endothelial cell injury, disturbed blood flow (stasis)
thromboembolism - results from DVT, embolus is a thrombus freely flowing in the blood stream
list the blood coagulation tests and explain what they test for
aPPT/PPT - measures efficacy of intrinsic and common pathway (I, II, V, VIII, IX, X, XI, XII)
citrated plasma and Ca2+ and phospholipid and kaolin
used to monitor heparin tx
normal range is 25-39sec
PT - measure efficacy of extrinsic and common pathways (I, II, V, VII, X)
citrated plasma and Ca2+ and tissue factor
used to monitor warfarin tx
normal range 12-15sec
INR - ratio of patient PT to healthy PT
normal range is 0.9-1.3
what is thrombocytopenia caused by and what can thrombocytopenia result in and what can you use to tx it
caused by damage or destruction of bone marrow (eg. malignancy or chemotx), results in spontaneous widespread hemorrhage visible by small purple spots on skin, treat with fresh whole blood transfusion or platelet transfusion
