blood physiology

1. Blood Physiology
Platelets and Hemostasis
Dr. Dina Hamdy Merzeban
Lecturer of Medical Physiology
www.facebook.com/merzeban physiology
http//:slideshare.net/ merzeban

2. Platelets
(Thrombocytes)
• Structure
• Platelets do not have nuclei.
• Platelets are discoid-shaped packages of
cytoplasm surrounded by a membrane.

3. • the membrane contains:
 large amount of phospholipids [(platelet
factor 3 (PF3)] which plays an important
role in clotting process.
 Receptors for collagen, V-W factor&
fibrinogen.
 Glycoprotein coat

4. • The platelet cytoplasm contains:
 actin and myosin (that can cause contraction
of the platelet - important in clot retraction).
2 types of granules
 Dense granules (Ca++, ADP, serotonin)
non- proteins.
 Alpha granules (factor XIII, PDGF, PAF)
proteins.

6. Properties of platelets
 Platelets do not have nuclei
 Platelet count: 250,000–500,000 platelets/cmm.
 Synthesis: in bone marrow from megakaryocyte by
budding, 30% stored in spleen.
 Life span of platelets: is 8 –12 days, average 10

7.  Thrombocytopenia: is a condition in which
the platelet count is greatly reduced
(aplastic anemia)
 Thrombocytosis (platelets count is greatly
increased as in (splenectomy)

8. Hemostasis
• Is the stoppage of bleeding

9. Steps of hemostasis
1) Vascular spasm
2) formation of a platelet plug,
3) formation of a blood clot as a result of blood
coagulation

11. Vascular spasm
• vasoconstriction is due to
Local myogenic contraction.
Nervous reflex due to pain (by sympathetic
stimulation).
Local humoral factors (ADP, serotonin &
thromboxane A2).

13. Platelet plug formation
Platelet adhesion
Platelet activation
platelet release reaction
Platelet aggregation
Platelet fusion:
Platelet procagulant activity

14. Platelet plug formation
 platelet adhesion:
 adhesion of glycoprotein coat of platelets to the
exposed sub endothelial collagen(VWF)
 platelet activation:
enhanced by ADP& thrombin.
Platelets swell, discharge their granules
 platelet release reaction

15. Platelet plug formation
platelet aggregation:
 released ADP, TxA2 cause more platelet to
aggregate to the site of vascular injury.
--->more release reaction--->More ADP, TXA2 --
-->more aggregation.
N.B.

16. Platelets plug formation

17. Platelet plug formation
 Platelet fusion:
irreversible fusion of aggregated platelet to
site of injury
helped by ADP, thrombin and enzymes of
platelet release.
 Platelet procagulant activity:
helped by platelet factor 3 (PF3).

20. Blood clotting
• The clot begins to develop in 15 to 20 seconds if the
trauma to the vascular wall has been severe
• formation of blood clot by conversion of the soluble
plasma protein fibrinogen to insoluble fibrin.
• Clot is formed of fibrin threads, blood cells and platelets.
• Coagulation factors are B globulins synthesized in liver
classified into 3groups

22. 1)Fibrinogen group:
 Factor (I, V, VIII, XIII)
 they are activated by thrombin.
 They are consumed during coagulation so, they are not
present in the serum.
2) Prothrombin group:
 (II, VII, IX, X)
 their synthesis in liver is VIT. K dependent.
 They are consumed during coagulation so, they are
present in the serum.
3)Contact group:
 XI, XII.
 They are not consumed during coagulation so, they are
present in the serum.

24. Clotting of Blood
• The blood contains about a dozen clotting
factors. These factors are proteins that exist in the
blood in an inactive state, but can be called into
action when tissues or blood vessels are
damaged. The activation of clotting factors
occurs in a sequential manner. The first factor in
the sequence activates the second factor, which
activates the third factor and so on. This series of
reactions is called the clotting cascade

25. Control of the Clotting
Cascade
• Thrombin is the key to the clotting mechanism. If
thrombin is present then clotting will proceeds, but if
thrombin is absent then clotting will not occur. How then
is thrombin controlled? Thrombin is derived from an
inactive precursor called prothrombin. There are two
pathways that lead to the conversion of prothrombin to
thrombin; (1) the intrinsic pathway and (2) the extrinsic
pathway.

27. Exrinsic pathway Intrinsic pathway

28. Interactions between extrinsic& intrinsic
system.
Factor X is common pathway.
 clotting is initiated by both systems.
Ca required for all steps except 1st two steps in
intrinsic pathway.
The extrinsic system (Factor VII) activates the
intrinsic system (Factor IX).
Once thrombin formed rapidly by extrinsic
pathway it activates factor V (in the intrinsic
pathway) which is the accelerator for
prothrombin activator complex leads to more
thrombin, more clot and vicious circle.

29. Fibrous organization or dissolution of the
blood clot
• Once a blood clot has formed, it can follow one of two
courses:
• (1) It can become invaded by fibroblasts, which
subsequently form connective tissue all through the clot,
or
• (2) it can dissolve

30. Anti- clotting mechanisms

31. Anti- clotting
mechanisms
The tendency of blood
to clot is balanced in
vivo by limiting
reactions that tend to
prevent clotting inside
the blood vessels and
to break down any
formed clots.

32. A.General limiting reactions.
 1. Smooth vascular endothelium, thus there is no
activation of platelets.
 2. Presence of heparin, which is a naturally occurring
anticoagulant.
 3. Removal of activated factors by liver and their
inactivation.

33. B. Specific limiting reactions.
1. The interaction between thromoboxane A2 and
prostacyclin:
• The interaction between the platelet-aggregating
effect of thromboxane A2, and the antiaggregating
effect of prostacyclin.
• This interaction causes a clot to form at the site of
injury but keeps the vessel lumen free of clot.
Note: aspirin increases prostacyclin prevent
platelet-aggregation , so given to prevent thrombosis.

34. B. Specific limiting reactions.
2. Antithrombin III:
protease inhibitor block activity of factors IX, X, XI,
XII.

35. B. Specific limiting reactions.
3. Fibrinolytic System

36. all endothelial cells except cerebral
microcirculation produce thrombomodulin which
is a thrombin binding protein.
Thrombin thrombomodulin complex is
anticoagulant which activate protein C.
Active protein C (APC) and its cofactor protein S
will:
a) inactivate factor V, VIII
b) inactivate an inhibitor of tissue plasminogen
activator TPA.
c) increase formation of plasmin which degrade fibrin.

37. Fibrinolytic System
 Plasminogen is converted to its active form plasmin,
by the action of tissue-plasminogen activator (t-PA).
 Plasmin (fibrinolysin) is an enzyme that lyses fibrin
and fibrinogen

38.  It is also activated by urokinase or
Streptokinse.
 Human t-PA is now produced by
recombinant DNA techniques for clinical use
in myocardial infarction and stroke.

39. Anticoagulants

40. In vitro anticoagulants
• used to prevent blood clotting outside the body.
a) Precipitation of Ca++ by oxalate or
deionization of Ca++ citrate.
b) Unwettable silicon coated tube to prevent
activation of platelet & XII.
c) Heparin.

41. In vivo anticoagulants:
Point of
Comparison
Heparin Dicumarol
• Origin: • Mast cells and
basophils.
• Plant
• Mode of
action:
• Facilitate action of
Antithrombin III.
• Inhibits formation of vitamin K
dependent clotting factors in the
liver
• Site of action: • In vivo & In vitro • Only in vivo.
• Onset: • Rapid onset. • Slow onset
• Duration: • Short duration • Long duration
• Administratio
n:
• Intravenous/
• intramuscular
• Orally
•
• Antidote: • Protamine sulfate
1%
• Vitamin K.

42. Abnormalities of Hemostasis:
There are three groups of abnormalities that can
occur in hemostasis:
A. Conditions that cause excessive bleeding
B. Conditions that cause excessive intravascular clotting.
C. Conditions that cause both excessive bleeding and intravascular
clotting.

43. A- Conditions that cause excessive
bleeding
1-Thrombocytopenic purpura:
This is due to deficiency of platelets, the symptoms
appear when platelet count decreases below
50,000/mm".
It is characterized by the presence many
subcutaneous hemorrhages called petechiae and
prolongation of bleeding time.

44. A- Conditions that cause excessive
bleeding
2-Vitamin K deficiency:
Vitamin K is a fat soluble vitamin synthesized by the
intestinal bacterial flora. It is needed for the formation of
factors, ll, VIl, IX and X by the liver. Deficiency of this
vitamin leads to decrease in the formation of these
coagulation factors and thus there is prolongation of
coagulation time.
Causes:
• Absence of intestinal bacterial flora which occurs in
new born infants
• Treatment with antibiotics for long periods in adults.
• Obstruction of biliary ducts which leads to absence of
bile needed for absorption of the vitamin.

45. A- Conditions that cause excessive
bleeding
3- Hemophilia:
• It is a congenital disease characterized by a
tendency for severe bleeding after mild trauma.
• It is a sex linked recessive disease carried by
females and manifested almost always in
males.
• It causes prolongation of the whole blood
coagulation time.

46. Conditions that cause excessive intravascular clotting
(Thromboembolic Conditions):
Causes:
1. Slow blood flow as occurs in leg veins due to
long bed rest after operations, or with varicose
veins
2. In atherosclerosis due to roughness or vascular
endothelium.

47. Conditions with both excessive bleeding
and intravascular clotting
Disseminated intravascular coagulation(DIC) :
• It is characterized by wide spread clotting accompanied
with bleeding tendency due to consumption of many
clotting factors.
• Causes:
• Retention of a dead fetus in the uterus for weeks
• Septicemia

48. Hemostatic Function Tests
1. Blood count and blood film: The platelet count is reduced in
thrombocytopenia.
2. Bleeding time: It is the time needed for bleeding to stop without
clotting of the blood. The normal bleeding time is 1-3 minutes and it
depends on platelet count and function. It is prolonged in
thrombocytopenic purpura.
3. Tests for blood coagulation:

49. Hemostatic Function Tests
3. Tests for blood coagulation:
 Whole blood coagulation time:
It is the time needed for blood to clot.
Normally, it is 3-10 minutes at 37 C. It is prolonged in
both vitamin K deficiency, hemophilia, and liver
diseases.
 The activated partial thromboplastin time (APTD):
Normally it is 30-40 seconds and is prolonged in
hemophilia.
 Prothrombin time: normal value is 15 seconds and
is prolonged in vitamin K deficiency.

50. Indications of transfusion
1. To restore whole blood as in
haemorrhage.
2. To restore one element e.g. RBCs,
WBC, platelets, plasma proteins, clotting
factors.
3. In erythroblastosis foetalis.

51. Precautions of transfusion
1. Compatible by cross matching.
2. Rh- person is transfused with Rh- blood.
3. Free from blood born diseases.
4. Free from contamination.
5. Fresh & with high Hb%.
6. Must be stored at 4 C for 21 days
maximum

52. Complication of transfusion
1. Agglutination
2. Physical: excessive transfusion→
overloading →HF.
3. Infective: e.g. infective hepatitis, AIDS or
malaria.
4. Mechanical: air or fat embolism.

53. Effects of incompatible blood
transfusion (Agglutination)
 Blockade of capillaries:-
Backache & joint pain
Angina pain (if coronary arteries are occluded).
 Hemolysis→ liberation of:-
1. Hemoglobin:
• increase blood viscosity → HF
• Jaundice
• Renal failure: death
2. Potassium: hyperkalemia → arrhythmia.
3. Toxic substances e.g. histamine → VD & shock