Dr Than Kyaw 13 February 2012 Cardiovascular System (CVS) L-2: Hematopoiesis, Blood Groups, &...
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Transcript of Dr Than Kyaw 13 February 2012 Cardiovascular System (CVS) L-2: Hematopoiesis, Blood Groups, &...
Dr Than Kyaw13 February 2012
Cardiovascular System (CVS)
L-2: Hematopoiesis, Blood Groups, & Hemostasis
HematopoiesisFormation of Blood Elements
● Mainly formed in the red marrow of many bones.● Also can be formed in liver, spleen and lymphatic
tissues.
Erythropoiesis
Leukopoiesis
Hematopoiesis
• All blood cells originate from pluripotent stem cells hemocytoblasts– The mother of all blood stem cells
• Hemocytoblasts differentiate into myeloid stem cells and lymphoid stem cells– Myeloid stem cells become myeloblasts or monoblasts
• Granulocytes formed from myeloblasts• Monoblasts enlarge and form monocytes
– Lymphoid stem cells become lymphoblasts• Lymphoblasts develop into lymphocytes
Hematopoiesis
Pluripotent stem cells(Hemocytoblasts)
Myeloid stem cells
Lymphoid stem cells
Myeloblast Monoblast
Granulocytes(Neutrophils,Eosinophils,
Basophils Monocytes
All blood cells originate from pluripotent stem cell hemocytoblasts
Rubriblast Megakaryoblasts Lymphoblast
ThrombocytesErythrocytes Lymphocytes
Hormonal control of erythropoiesis
Erythropoietin
(glycoprotein
produced by kidney)
Bone marrow
Erythropoiesis
Hypoxia (decreased RBCs)Decreased O2 availabilityIncreased tissue demand for O2
Adequate supplies of iron, amino acids, and B vitamins
Stimulate
• Erythropoiesis requires:– Proteins, lipids, and carbohydrates– Iron, vitamin B12, and folic acid
• The body stores iron in Hb (65%), the liver, spleen, and bone marrow
• Intracellular iron is stored in protein-iron complexes such as ferritin and hemosiderin
• Circulating iron is loosely bound to the transport protein transferrin
ErythropoiesisDietary Requirements
Blood Groups and Transfusions• Large losses of blood have serious consequences
• Loss of 15 to 30 % causes weakness
• Loss of over 30 % causes shock, fatal
• Transfusions are the only way to replace blood quickly
• Seldom practiced in animal
· Transfused blood must be of the same blood group
· Wrong group: dead patient
· First done: William Harvey, England (about 1600)
• Animals and human
- a variety of different blood types• In human – usually only 4 types of groups used
Blood groups in animals and man
Blood Groups of some animals
Animal spp Blood groups
Cattle A, B, C, F, J, L, M, R, S, T, Z 11
Goats A, B, C, M, J 5
Sheep A, B, C, D, M, R and X 7
Horse 8 major groups (A, C, D, K, P, Q, U, T) Over 30
Cat A, B, AB 3
Dog DEA 1.1, 1.2, 4, 5, 6,7, 8 8
Human A, B, AB, O 4
DEA=Dog Erythrocyte Antigen
• RBCs carry genetically determined proteins
• Called agglutinogens or antigens (Ag)
• Proteins embedded in cell membrane
• A foreign protein (Ag) may be attacked by the immune system
• Two types of antigens
Type A
Type B
• Based on presence / absence of antigens A & B
Type AB (presence of both antigens - A & B)
Type O (absence of both antigens - A & B)
Blood groups & blood typing in man
• Two types of antibodies - Agglutinins (Ab)
Anti A and Anti B• Blood typing is done based on antigen-antibody reaction
Blood groups & blood typing in man
• When serum containing anti-A or anti-B agglutinins is added to blood, agglutination will occur between the agglutinin and the corresponding agglutinogens
• Agglutination - Positive reactions
Blood type being tested
RBC agglutinogens Serum Reaction
Anti-A Anti-B
AB A and B + +
B B – +
A A + –
O None – –
Blood groups & blood typing in man
Rh Blood Groups
· Depends on presence or absence of Rh antigens (agglutinogen D)
· Problems can occur in mixing Rh+ blood into a body with Rh– blood
· Called hemolytic disease of the newborn or Erythroblastosis fetalis
· Danger is only when · the mother is Rh– · the father is Rh+
· the child inherits the Rh+ factor
Rh Dangers During Pregnancy
· Mom’s immune system is sensitized · Makes antibodies against Rh+
· In a subsequent pregnancy: · Mother’s blood carries antibodies· Anti-Rh antibodies cross placenta· Attack the Rh+ blood in the fetus
· Because immunity development takes time – the first baby may not be affected.
What will happen to the Rh+ baby?
Fig. 11.13
Hemostasis and coagulation
Hemostasis – stoppage of bleeding
Involve 3 basic reactions
1. constriction of smooth m/s of blood vessels to reduce openning
2. Formation platelet plug to occlude the opening
3. Clot formation to complete occlusion of the opening
Hemostasis and coagulation
• Platelets adhere to collagens and other proteins in the damaged C/T, release secretory granules*
• The surface of damaged blood vessel – losses its smoothness and nonwetatability that attract platelets to be adhered
• These activated platelets stimulate other platelets to those already present, thus making platelet plug
• May be sufficient to occlude very small vessels
* granules and dense granules: containing many of the coagulation factors, proteins, calcium, serotonin, ADP, ATP; all assist or potentiate the coagulation process
• Platelets aggregation – regulated by 2 eicosanoids
- Thromboxane A2 (TXA2) and
- Prostacyclin (PGI2)
• TXA2 – secreted by adhered platelets and stimulate platelet aggregation
• PGI2 – secreted by intact undamaged endothelial cells
- acts to stop the growth of platelet plug.
• TXA2 and serotonin (also secreted by adhered platelets)
– vasoconstrictors stimulating smooth m/s constriction to assist with hemostasis
Hemostasis and coagulation
* Aspirin block the formation of TXA2
Hemostasis and coagulation
• For more serious or large vessel damage Clot or Thrmbus formation, in addition to platelet aggregation, is necessary
• Clot – relatively solid gel plug
- a fibrin mesh and entraps the plug
• If the plug contains only platelets - a white thrombus
• If red blood cells are present - a red thrombus.
• Finally, the clot must be dissolved in order for normal blood flow to resume following tissue repair.
• The dissolution of the clot occurs through the action of plasmin.
4 key reactions in the clot formation
1. Activation of factor IX
2. Activation of factor X
3. Formation of thrombin and
4. Fibrin formation
Major components of coagulation pathway
Component Synonym Site of synthesis
Fibrinogen Factor I Liver
Prothrombin Factor II Liver
Thrombin Plasma
Tissue factor Thromboplastin Vascular endothelium
Factor V Vascular endothelium
Factor VII Liver
Factor VIII Antihemophilic factor Vascular endothelium
Factor IX Christmas factor Liver
Factor X Stuart factor Liver
Factor XI Plasma thromboplastin antecident
Liver
Factor XII Hageman factor Liver
Factor XIII Fibrin stabilizing factor Vascular endothelium
Calcium Factor IV
Intrincsic system
TF
Extrincsic system
Contact activation pathwayTissue factor (TF) pathway
VII
TF-VIIa complex
Endothelial damage
X Xa
IX
IXa - VIIIa –PL- Ca2+
Tenase complex
X
Surface contact
VIII
Xa - Va –PL - Ca2+
Prothrombinase complex
V
Prothrombin Thrombin
FibrinFibrinogen
Positive feedback
Endothelial contact
XII XIIa
XI XIa
IX IXa
IXa - VIIIa –PL- Ca2+
Tenase complex
Fig. 11.9
Fibrin (polymerized protein)
Soluble form
Fibrinogen
Thrombin + Ca2+
XIIIa XIII
Insoluble Fibrin (Stable fibrin, more elastic and less subject to lysis )
Fibrin formation
Clot retractionShrinking of the clot
By the action of
1.Platelet contractile protein
2.Thrombosthenin
3.Actin
4.Myosin
Retraction – squeeze serum
- greater blood flow
Removal of fibrin
After establishment of hemostasis – damaged area repaired by new tissue growth assisted by growth factors released by platelets- Fibrin undergoes degradation (fibrinolysis) by proteolytic enzyme plasmin
PlasminPlasminogen(Plasma protein)
t-PA (Tissue type plasminogen
activator)
Fibrin FDPs(Fibrin degradation
products)
FDPs, removed by MPS
MPS – mononuclear phagocytic system