1. Cardiovascular System (CVS)
L-2: Hematopoiesis, Blood Groups, & Hemostasis
Dr Than Kyaw 13 February 2012

2. Hematopoiesis Mainly formed in the red marrow of many bones.
Formation of Blood Elements
Erythropoiesis
Hematopoiesis
Leukopoiesis
Mainly formed in the red marrow of many bones.
Also can be formed in liver, spleen and lymphatic tissues.

3. 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

4. All blood cells originate from pluripotent stem cell hemocytoblasts
Pluripotent stem cells
(Hemocytoblasts)
Myeloid
stem cells
Lymphoid
stem cells
Rubriblast
Megakaryoblasts
Myeloblast
Monoblast
Lymphoblast
Granulocytes
(Neutrophils,
Eosinophils,
Basophils
Erythrocytes
Thrombocytes
Monocytes
Lymphocytes

7. Hormonal control of erythropoiesis
Erythropoietin (glycoprotein produced by kidney)
Hypoxia (decreased RBCs)
Decreased O2 availability
Increased tissue demand for O2
Stimulate
Bone marrow
Adequate supplies of iron, amino acids, and B vitamins
Erythropoiesis

9. Erythropoiesis Dietary Requirements
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

10. 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)

11. Blood groups in animals and man
Animals and human
- a variety of different blood types
In human – usually only 4 types of groups used

12. 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

13. Blood groups & blood typing in man
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)

14. 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
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

16. Blood type being tested
Blood groups & blood typing in man
Blood type being tested
RBC agglutinogens
Serum Reaction
Anti-A
Anti-B AB
A and B + B – A O
None

17. 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

18. 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?

20. 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

21. 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

22. Hemostasis and coagulation
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
* Aspirin block the formation of TXA2

23. 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.

24. 4 key reactions in the clot formation
Activation of factor IX
Activation of factor X
Formation of thrombin and
Fibrin formation

25. Major components of coagulation pathway
Synonym
Site of synthesis
Fibrinogen
Factor I
Liver
Prothrombin
Factor II
Thrombin
Plasma
Tissue factor
Thromboplastin
Vascular endothelium
Factor V
Factor VII
Factor VIII
Antihemophilic factor
Factor IX
Christmas factor
Factor X
Stuart factor
Factor XI
Plasma thromboplastin
antecident
Factor XII
Hageman factor
Factor XIII
Fibrin stabilizing factor
Calcium
Factor IV

26. Extrincsic system Intrincsic system Tissue factor (TF) pathway
Contact activation pathway TF
VII IX
Endothelial damage
Surface contact
TF-VIIa complex
IXa - VIIIa –PL- Ca2+
VIII
Tenase complex X Xa X
Positive feedback
Xa - Va –PL - Ca2+ V
Prothrombinase complex
Prothrombin
Thrombin
Fibrinogen
Fibrin

27. Endothelial contact
XII
XIIa XI
XIa IX
IXa
IXa - VIIIa –PL- Ca2+
Tenase complex

29. Fibrin formation Fibrinogen Fibrin (polymerized protein) Soluble form
Thrombin + Ca2+
XIIIa
XIII
Insoluble Fibrin
(Stable fibrin, more elastic and less subject to lysis )

30. Clot retraction
Shrinking of the clot
By the action of
Platelet contractile protein
Thrombosthenin
Actin
Myosin
Retraction – squeeze serum
- greater blood flow

31. MPS – mononuclear phagocytic system
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
t-PA
(Tissue type plasminogen activator)
Plasminogen
(Plasma protein)
Plasmin
Fibrin
FDPs
(Fibrin degradation products)
FDPs, removed by MPS
MPS – mononuclear phagocytic system