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 groupsCattle 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 antigensType AType B

• Based on presence / absence of antigens A & BType 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 opening3. 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 IX2. Activation of factor X3. Formation of thrombin and 4. Fibrin formation

Major components of coagulation pathwayComponent 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 complexV

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 of1.Platelet contractile protein2.Thrombosthenin3.Actin4.Myosin

Retraction – squeeze serum - greater blood flow

Removal of fibrinAfter 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