Presentation on the physiology of Human Blood.

1. Контактна інформація:
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Blood physiology
Dr. Ivan Dzis, PhD, as. prof.

2. Blood functions
Blood is a type of liquid
connectivetissue.
The major function of blood
is transport.

3. Subfunctions
 Respiration :
-if oxygenand carbon dioxide aretransported
 Trophic :
-when the nutrient materialsaredelivered to
the tissues
 Excretive :
-when the metabolites are deliveredfrom
tissues to excretoryorgans
 Regulative :
-if the hormones and biologically active
substances (BAS) aretransported

4. Subfunctions
 Homeostatic :
- maintenance of water content andacid-base
balance
 Protective :
- immunity and non-specificresistance;
- blood coagulation
 Maintenance of body temperature:
-as a result of a redistribution of blood volume
between skin and the internal organs at high and low
temperature of externalenvironment.

5. Blood as a system
Blood
(peripheral
Organs forhaemopoiesis
and destructionof
& circulating) blood
Regulatory
apparatus
(nervous
& humoral)

6. The total blood volume makes up
about 6-8 percent of the body’sweight.
Accordingly, a 70-kilogram personwill
have 5 to 6 litres of blood.
Circulating blood volume will be lesser
than total blood volume, becausesome
amount of blood will be deposited in
organs like liver.

7. Blood composition
Blood consistsof
liquid plasma
(volume-55-60%)
formed elements(cells)
(volume-40-45%)

8.  Formed elements include
Erythrocytes (red blood cells);
Leukocytes (white bloodcells);
Thrombocytes (platelets)

9. Hematocrit
The hematocrit , also
known as packed cell
volume (PCV)
or erythrocyte volume
fraction (EVF), is the
volume percentage (%)
of red blood cells in the
blood. It is normally
about
40-48% for menand
36-42% forwomen

10. Hematocrit
 If a portion of blood is centrifuged or
allowed to stand for a sufficient long
time, itwill be found that the blood cells
will settle towards the bottom of thetest
tubewhile the plasmaremainson top.
 By this means the percentage of blood
cells in whole blood can bedetermined.

11. Haemopoiesis
 Haemopoiesis is theformation
of blood cellular components. All cellular
blood components arederived
from pluripotent haemopoietic stemcells
which is present in the bonemarrow.
 In a healthy adult person, approximately
1011–1012 new blood cells are produced daily in
order to maintain steady state levels in the
peripheral circulation.

12. Haemopoiesis

13. Blood Composition

14. Regulation of haemopoiesis
 Humoral regulation byhormones:
 Erythropoietin
 Leucopoietin
 Thrombopoietin
 These hormones are produced bykidney
and liver.

15. Blood plasma
 Composition :
90-92% of water
8-10% of dry substance
mainly consisting from proteins (6-8%)
Dry substance includes:
inorganic (mineral)
organiccomponents

16. Blood plasma
 The main (inorganic) mineral components:
(0.9-1.5 %):
Cations : Anions :
Chlorides(Cl⁻)
Phosphates (PO4⁻)
Bicarbonates(HCO3⁻)
 Sodium (Na+),
 Potassium (K+),
 Calcium (Ca++),
 Magnesium (Mg++)

17. Blood plasma
 The organic components ofplasma
include :
proteins
lipids
carbohydrates

18. Plasma proteins and their role
 Plasma proteins include:
 Albumin -
(65-85 g/l)
Transportation
Regulation of oncotic pressure
Regulation of pH
α
β - Transportation
γ - Defense
Blood clotting (haemostasis)
 Globulin -
(28 g/l)
 Fibrinogen-
(3 g/l)

19. Lipids and carbohydrates in plasma
 The major plasma carbohydrate is glucose
(3.3-5.5 mmol/L)
 Plasma normally contains varying amounts of
hormones, enzymes, pigments, and vitamins.
 The composition of plasma varies withthe
body’s activity and different physiological
states.

20. Serum
When fibrinogen is removed from
plasma as a result of coagulation,
such plasma without fibrinogenis
called serum.

21. Physico-chemical constants of blood
 Osmotic pressure
 Oncotic pressure
 Blood pH
 Viscosity
 Specific gravity
 Erythrocyte sedimentation rate(ESR)

22. Osmotic pressure (~7.6 atm)
 Osmotic pressure :
-is defined as the minimum amountof
pressure needed to prevent osmosis*.
 Dissolved particles maintain the osmotic pressure.
 Among them, the most activeis
-NaCl (0.9 % isotonic)
- and alsoglucose (5 % isotonic).
 In hypotonicsolution
- swelling and bursting occurs.
 In hypertonicsolution
- shrinkageoccurs.
*Osmosis is the spontaneous net movement of solvent molecules
through a semi-permeable membrane into a region of higher solute
concentration, in the direction that tends to equalize the solute
concentrations on the two sides

23. Osmotic pressure

24. Oncotic pressure
 Oncotic pressure, or colloid osmotic pressure,
is a form of osmotic pressure exerted by blood
plasma proteins. It usually tends to pull water
(fluid) into the circulatorysystem(capillaries).
 It is the opposing force to hydrostaticpressure
 Its normal value is :
0.03-0.04 atm
(or)
20-25 mm Hg

25. pH of blood
 pH isa measureof theacidityoralkalinity
of an aqueoussolution.
 It is the negative decimal logarithm ofhydrogen
concentration
 Normal pH of blood is :
(arterial blood) 7.45 – 7.35 (venous blood)
 If pH is less than 7.3 , it is acidosis
 If pH is more than 7.5, it is alkalosis

26. pH of blood is maintained by :
 The excretion of carbon dioxide by thelungs
 The excretion of H+ or OH- by the kidneys.
 By the action of buffer system
Carbonate Haemoglobin
Phosphate
( HA
Protein
H⁺ + A⁻ )

27. Viscosity
 Blood viscosity can be described as the thickness
and stickiness of blood.
 It is a measureof the resistanceof blood to flow.
 Theviscocityof blood is 5 times more than thatof
water
(based on time taken forthe flow of both in a
tube)
 It depends on:
RBCs
Plasmaproteins

28. Specific gravity
 Specificgravity is the ratioof
thedensityof asubstance to thedensity
of a referencesubstance.
 Specificgravity isalsocalled relative
density.
Blood normally hasaspecific gravityof :
1.05 - 1.06 g/L

29. Specific gravity
 Specific gravity depends on:
RBCs Plasma proteins
 The higher theconcentrationof RBCsand plasma
proteins, higher will be the specificgravity.
1.03 1.04 1.05 1.06

30. Erythrocytes (RBC)
 Red blood cells, orerythrocytes, are the
most abundant type of bloodcell.
 Approximately 2.4 million new
erythrocytes are produced per second.
 Approximatelyaquarterof thecells in
the human body are red bloodcells.

31. RBC -Structure
 In humans, mature red blood cells are
oval biconcave disks and they are
flexible
 A typical humanerythrocyte hasadisk
diameter of approximately 6.2–8.2µm
 They lack a cell nucleus and
most organelles, in order to
accommodate maximum spacefor
haemoglobin.

32. RBC
 Since RBCs have a elastic membrane, theyare
able to change their shape when they pass
through thecapillaries.
 The cells develop in the bone marrow and
circulate for about 100–120 days in thebody
before their components are recycled
by macrophages.
 Human red blood cells take on average
20 seconds to complete one cycle of
circulation.

33. RBC Count
 Normal range:


In male : 4.0-5.0 × 1012/L
In female : 3.5-4.5 × 1012/L

34. RBC - Functions
 The major function of thesecells isa transport
of haemoglobin, which in turn carries oxygen
from lungs to thetissues
 Red blood cells contain carbonic anhydrase,
which catalyzes the reaction betweencarbon
dioxide and water, that has a significance in
transporting carbon dioxide (CO2) from
tissues tolungs.

35. RBC - Functions
 The haemoglobin isan excellentacid-
base buffer.
 Maintanence of acid-basebalance.
 Blood groupdetermination.

36. Erythropoiesis
 Erythropoiesis is the process by whichred
blood cells (erythrocytes) areproduced.
 It is stimulated by decreased O2 incirculation,
which is detected by the kidneys, which then
secrete the hormoneerythropoietin.
 The whole process lasts about 7 days.Through
this process erythrocytes are continuously
produced in the red bone marrow of large
bones, at a rate of about 2 million per second
in a healthyadult.

37. 1. Hemocytoblast differentiates into myeloid stem cell followed by
many stages of differentiation, that involve protein synthesis
2. As cell fills with Hb, it loses organelles (nucleus too)
3. After 3-5 days reticulocytes are formed (Hb + some ribosomes),
released into blood, 1-2% of total blood RBCs
4. After 2 days in circulation RBC lose ribosomes (no more protein
synthesis) -mature erythrocyte
Vitamin B12 is necessary for erythropoiesis for stem cell division
Lack of B12 - pernicious anemia (B12-deficiency anemia)
Erythropoiesis

38. Erythrocyte Recycling
-old/damaged RBCs removed by phagocytes in spleen
-phagocytosed cells broken down: -protein ! amino acids,
released for use -heme !
1. iron removed, bound to transferrin in blood for recycling
back to bone marrow (new RBCs)
2. pigment ! biliverdin (green) bilirubin (yellow-green),
released into blood, filtered by liver, excreted in bile
Jaundice = failure of bilirubin to be excreted in bile,
collects in peripheral tissues ! yellow skin & eyes
3. in gut, bilirubin ! urobilins (yellow) & stercobilins
(brown) via bacteria urobilins absorbed, excreted in
urine stercobilins remain in feces Hemolysis = RBC
rupture in blood ! Hemoglobinuria = red/brown urine
due to kidney filtering intact chains of hemoglobin

39. Erythrocyte Sedimentation Rate
(ESR)
 The erythrocyte sedimentation rate (ESR), is
the rateatwhich red blood cells sediment in a
period of one hour.
 RBC and plasma will beseparated.
 It is a common hematology test.
 Normal values :
Men -
Women -
2-10 mm/hr
2-15 mm/hr

40.  Increased ESR may be due to:
Pregnancy
Inflammation
Cancer
 Decreased ESR may be due to:
Polycythemia Sickle
cellanemia
Hereditaryspherocytosis
Congestive heart failure

41. Haemolysis of RBCs, its types
 Haemolysis is the rupturing of
erythrocytes and the release of their
contents (cytoplasm) intosurrounding
fluid (blood plasma).
 Hemolysis mayoccurinvivoor in
vitro (insideoroutside the body).

42. Haemolysis of RBCs
 Causes :
• Inherited defects of RBC’s
• (e.g., Hereditary spherocytosis ,Thalassemia)
• Chemicals, poisons
• Infections (the toxic products of
microorganisms
• Transfusion of the wrong blood type or Rh
incompatibility of fetal and maternal blood,
a condition called erythroblastosis fetalis.

43. Haemoglobin - Structure
Content :
It is composed of the
protein globin (a
polypeptide), and the
pigment heme.
Structure :
The haemoglobin has the
ability to combine with
oxygen due to the four iron
atoms associated with
each heme group within
themolecule.
ADULT HEMOGLOBIN (HbA) has 4 polypeptide chains (2 pairs of α
chains and 2 pairs of β chains) and 4 heme groups (porphyrin and iron)

44. Haemoglobin
Physiological role :
The main function oferythrocytes
is carried out by meansof
haemoglobin.
Normal range of haemoglobin :
In men
Inwomen
- 135-180 g/L
- 120-140 g/L

45. Compounds of haemoglobin
 Physiological associations of haemoglobin :
 Oxyhemoglobin :
- Oxygen combines weakly with the
haemoglobin molecule. Such association
is called oxyhemoglobin . It is formed in
lungs.
 Deoxyhemoglobin :
- When the oxygen is released to the tissues
of the body, the haemoglobin is called
reduced haemoglobin or
deoxyhemoglobin.
 Carbhemoglobin :
- In tissues Hbcombineswithcarbon dioxideand
formcarbhemoglobin.

46. Compounds of haemoglobin
Pathological combinations of haemoglobin :
 Carboxyhemoglobin - is combination of
hemoglobin and carbon monoxide. It is gas
without smell and color thateasily associates
with hemoglobin (more easily thanoxygen).
 Methemoglobin - is such hemoglobin in
which iron has potential not +2 asusually,
but +3. Such iron creates strong chemical
connection and not able to provide tissues
with oxygen.

47. Types of haemoglobin
 Embryo has HbP (primitive) - (α2ε2)
 Adults have HbA - (α2β2)
 Fetal hemoglobin (HbF)-Before birth(α2γ2)
The fetal hemoglobin (HbF) isdifferent
from the adult type(HbA)
It has moreaffinity tooxygenand can
besaturated withoxygenata lower
oxygentension.
In infants, the hemoglobin molecule is madeupof 2 α chains
and 2 γ chains. The gamma chains are gradually replaced by β
chains as the infant grows.

48. Iron deficiency anemia
• Excessive loss of iron
Megaloblastic anemia
• Less intake of vitamin B 12 and folic acid
• Red bone marrow produces abnormal RBC. e.g cancer drugs
Pernicious anemia
• Inability of stomach to absorb vitamin B 12 in small intestine
Hemorrhagic anemia
• Excessive loss of RBC through bleeding, stomach ulcers, menstruation
Hemolytic anemia
• RBC plasma membrane ruptures
• May be due to parasites, toxins, antibodies
Thalassemmia
• Less synthesis of hemoglobin. Found in population of Mediterranean sea.
Sickle cell anemia
• Hereditary blood disorder, characterized by red blood cells that assume an
abnormal, rigid, sickle shape
Aplastic anemia
• Destruction of red bone marrow
• Caused by toxins,gamma radiation
Types of anemia

49. Colour index
 The average content of hemoglobinin
one erythrocyte is called color
parameter of blood.
 Formula :
Colourindex = Haemoglobin content(g/L) ×3
First three numerals of RBCcount
 It fluctuates between 0.8 - 1 unit.
 If less than 0.8 - Hypochromia,
 If more than 1 - Hyperchromia.

50. Leucocytes (WBC)
 White blood cells havenuclei
 Size 9-12 μk
 They makeupapproximately 1% of the
total blood volume in a healthyadult.
 They live forabout three to fourdays in
the average humanbody.
 Normal count of WBC:
4-9 x 109/L

51. Leucocytes-functions
The major function of leucocytes is:
Protective function.
It provides immunity andthus
defends the body.

52. Leucopoiesis
 It is the process
leucocytes
production
 Leucocytes are
produced from
pluripotent
haemopoietic stem
cell, present in bone
marrow
 Differentiation of
lymphocytes - in the
lymphtissue.

53. Role of Leucopoietins
These are hormones produced by
liver and kidney
They provide humoral regulation
of leucopoiesis.

54. Leucocytosis
 Increased amount of leucocytes in blood.
 It may be :
Pathological
Inflammation
Cancer
Physiological
Food intake
Exercises
Emotion
Stress

55. Leucopenia
 Abnormally low concentration of leucocytes in
blood.
 Only pathological :
Severe viral infections
Autoimmune disease
Chemotherapy
Radiation injury

56. Types of leucocytes
Leucocytes are of 2 types :
Agranulocytes :
Monocytes
Lymphocytes
Granulocytes :
Neutrophils
Basophils
Eosinophils

57. Neutrophils (2.5–7.5 x 109/L)
Neutrophils :
 47 - 72%
 Juvenile(band) – 6% ,
 Immature(young) – 1% ,
 Segmented – 47-72%
 Functions :
• First lineof defense (firstcells thatcome
to the area of inflammation).
• Multi functional cells that attack and
destroy viruses and bacteria.

58. Neutrophils
Phagocytosis - cellularingestion of bacteria with
enzymes proteases, peroxidases,cationic proteins
Degranulation - release defensins, lyse bacteria
Respiratory burst – also called oxidative burst is the rapid
release of chemicals from immune cells when they
encounterwith a bacteriaor fungi.It is a crucial reaction
that occurs in phagocytes to degrade internalized
particles and bacteria.
Leukotrienes - attract phagocytes (polymorphonuclear
leukocytes) - non-specific defense

59. Basophils (0.01-0.1 x 109/L)
Basophils contain :
 Histamine – for vasodilation
 Heparin – anticoagulant
 Has IgE and thus participates inallergic
reaction along with mast cells intissues
 Promotes functions of otherleucocytes

60. Eosinophils (0.04-0.4 x 109/L)
Eosinophils- Functions :
• Phagocytosis of antibody covered objects
• Defense against parasites: release exocytose
toxins on large pathogens
• Reduce inflammation: by anti-inflammatory
chemicals/enzymes action
• Contains histaminase that reduces allergic
reaction
Eosinophilia – increased level of eosinophils in the
blood.

61. Monocytes (0.2–0.8 x 109/L)
Monocytes - Functions :
 They differentiate into macrophages
 Antigen – presentationfunction.
Monocytes
Wandering
Goes to the siteof
inflammation.
In tissues
Kupffercells
Alveolarmacrophages
Microglia

62. Lymphocytes (1.5–3.5 x 109/L)
 Provides immunity.
 Threetypes : B – lymphocytes, T- lymphocytes, NK-
lymphocytes.
 B – lymphocytes provide humoral immunity.
 T – lymphocytes provides cell-mediatedimmunity.
 NK cells - immune surveillance (destroy abnormal
tissue)
 B – cellsdifferentiate into plasmacellswhich further
produces 5 classes of antibodies that provide
immunity
 T- cytotoxiccellsaims toeliminate :
•Virus-infected cells
•Cancer cells
•Cause graft rejection.

63. Diagnostic importance
 ↑Neutrophils – inflammation
 ↑Eosinophils – allergy,parasitic
infections
 ↓ Eozinophils – stress
 ↑ Lymphocytes – cancer (leukemias–
cancerousproduction of lymphoid
cells)

64. Leucogram- Normal count
Total no.
of leuco
cytes
Eosinop
hils
Basophil
s
Juvenile
(band)
neutrop
hils
Immatur
e
neutroph
ils
Segment
ed
neutroph
ils
Lympho
cytes
Monocy
tes
Normal
Range
4-9 x
109/L
0.5-5% 0- 1% 6% 1% 47-72% 19-37% 3-11%

65. Plasma proteins
Albumins (60% or 38-60 gr/) – most protein homogeneous fraction of plasma
Function :
• oncotic pressure (25-30 mm n. mercury or 0,03-0,04 atm)
• water exchange between vessels and ECS
• depot of nutritians
• buffer system for pH balance of blood
• bind fatty acids
Globulins (20-30 gr/l) – oncotic pressure. Via electrophoresis are split for α1, α2,
β, ϒ
α1- globulins (1,4 – 3,0 gr/l) – glucose transport (60%), phospholipides,
cortisol, vitamin B12
α2- globulins (5,6 – 9,1 gr/l) – blood copper transport (90%), oxidase
ability
β - globulins (5,4 – 9,1 gr/l) – lipoprotein transport
ϒ - globulins (9,1 – 14,7 gr/l) – IgA, IgG, IgM, IgD, IgE. Defence factors –
antybodies.
Fibrynogen (2-4 gr/l) – a globulin, basis for trhomb in clotting activation

66. Agglutination of RBCs
 The agglutination of RBCs due to binding of
antibody with the corresponding antigen is
called haemagglutination.
 Example:
Anti-A binds A antigenand anti-B binds B antigen
 It has two common uses:
• Blood typing
• The quantification of virus dilutions.

67. Agglutination
 Agglutinogens (antigens) are proteinsthat
exist on the surface of every red bloodcell.
 This agglutinogen , which is present on the
surface of RBCs, will stimulate theproduction
of agglutinin (antibody) in the plasma in case
of incompatible blood transfusion.
 Helps in determining the blood type ofa
person.

68. ABO blood group system
 According to the ABO blood typing
system thereare fourdifferent kindsof
blood types: O, A, B, AB.
 I(O) - α,β (40%);
 II(A) - β (39%);
 III(B) - α (10-15%);
 IV(AB) - 0 (5%).

69. ABO blood group system

70. CDE blood group system
 Out of C,D and E D is the strongestantigen.
 Also called Rhesus (Rh) system
 85% of the population is - Rh⁺
 If Rh-D antigen is present in blood(RBC) - Rh⁺
 If Rh-D antigen is absent inblood(RBC) - Rh⁻
 It is determined by anti-Rhserum.

71. Rh incompatibility
 In blood transfusion :
Rh⁻ personcannot receive blood from Rh⁺ person,
whereas Rh⁺ person can receive blood from Rh⁻
person
 If a Rh⁻ person receive bloodfrom Rh⁺ person for the
first time, due to this exposure, there will be
formation antibodies(anti-RhD)
 So, if a second transfusion is done again with Rh⁺
blood, then, theantibodieswhich arealreadypresent
cause agglutination of RBC

72. Rh incompatibility
 Erythroblastosis fetalis :
Rh- mom pregnant with Rh+ baby, gets exposed to D
antigen during birth, leads formation of anti-D
antibodies. During consecutive pregnancies, thismay
cause destruction of RBCs in the fetus causing
haemolytic anaemia (erythroblastosis fetalis). So after
each pregnancy, the mother should receive anti-RhD
(prophylaxis)to prevent thisincompatibility.

73. Blood transfusion
 Blood transfusion:
The process of receiving blood products into one's
circulation intravenously. Transfusions are usedin a
variety of medical conditions in order to replace the lost
components of the blood. Early transfusions
used whole blood, but modern medical practice
commonly uses only components of the blood, such
as red blood cells, white blood cells, plasma,clotting
factors, and platelets.

74. Rules of blood transfusion
 Check for ABO blood group compatibility.
 Check for Rhesus (Rh factor)compatibility.
 Cross-match(individual tests):
By taking RBC from donor and plasma from
recipient. Agglutination must beabsent.
 Biological test :
Three times introducing donor’s blood in small
portions like -10-25 ml into therecipient and check for
any complaints or deviation of physiological
parameters.
If blood type unknown: blood type I(O) - universal
donor: it lacks all 3 agglutinogens (A, B, D) so risk of
agglutination by antibodies is minimal

75. Thrombocytes (platelets)
 Fragments of megakaryocytes (red bone marrow)
 Cell fragments (nonucleus)
 2–3 µm indiameter
 Normal range : 180-320 x109/L
 Constantly replaced, 9-12 d in circulation, then
phagocytosed by cells in spleen
 1/3 of total platelets held in reserve in spleen,
mobilized for crisis

76. Platelets functions
• transport clotting chemicals, release
when activated
• form patch (platelet plug) over damaged
vessel
• contract wound after clotting (contain
actin and myosin)

77. Thromocytopoiesis
 Platelets are produced in bone marrow, by budding
off from megakaryocytes.
 Megakaryocyte and platelet production is regulated
by thrombopoietin, a hormoneusually produced by
the liver andkidneys.
 Each megakaryocyte produces between 5,000and
10,000 platelets.
 Around 1011 plateletsareproduced each day byan
average healthyadult.
 Reserve plateletsarestored in thespleen, and are
released when needed by sympathetically induced
spleniccontraction.
 Old plateletsare destroyed by phagocytosis in the
spleenand by Kupffercells in the liver.

78. Haemostasis
 Haemostasis is a process which causes bleeding to
stop, meaning to keep blood within a damagedblood
vessel .
 It is the first stageof wound healing. Mostof the time
this includes blood changing from a liquid to a solid
state
 Hemostasis has three major steps:
o Vasoconstriction
o Temporary blockageof a lesion bya platelet plug
o Blood coagulation, or formationof aclot that seals
the lesion until tissues are repaired

79. Haemostasis - its types
 Twotypes :
 Vascular-platelet hemostasis :
Stoppage of blood loss from themicrocirculatory
vessels having low blood pressure.
Platelet plug isformed
 Coagulation hemostasis:
Stoppage of blood loss from the large vessels
having higher blood pressure.
Blood clot isformed

80. Vascular-platelet hemostasis
Vessel is injured
Vasoconstriction due to nervousreflex
Von-Willebrand factor
Adhesion of platelets to collagen - Positivefeedback
(plateletsundergoshapechangeand releaseADP and ATP, Ionized
calcium, Serotonin, Epinephrine, Thrombaxane A2 fromgranules)
(Primary) Temporary plateletplug
(Stable) Permanent platelet plug – morestable
Adhesion
Secretion
Aggregation

81. Cellular (platelet) clotting factors
 Cellularclotting factorsarepresent in thegranules of
thrombocytes.
 These factorsarereleased when the platelets undergo
degranulation. They are:
• ADP and ATP (adhesiveness and aggregation)
• Ionized calcium (helps in factors binding to
phospholipids in platelets)
• Serotonin & Epinephine (local vasoconstriction)
• Thrombaxane A2

82. Coagulaton cascade
(hemostasis)

83. • The intrinsic pathway requires only clotting factors found
within the blood itself—in particular, clotting factor XII
(Hageman factor) from the platelets. It is a longer,
multistep pathway and it takes a little longer for the blood
to clot by this mechanism. Although it is a natural clotting
process in the body, it also is the sole mechanism of
clotting when blood is drawn into a clean test tube
without anticoagulants.
• The extrinsic pathway is initiated by factors external to
the blood, in the tissues adjacent to a damaged blood
vessel. In particular, it is initiated by clotting factor III,
thromboplastin, from the damaged tissues. It involves
fewer chemical reaction steps and produce a clot (fibrin) a
little more quickly than the intrinsic pathway.
Differences

84. Plasma clotting factors (12)
 Factor number Name
 I
 II
 III
 IV
 Va
 VII
 VIII
 IX
 X
 XI
 XII
 XIII
-
-
-
-
-
-
-
-
-
-
-
-
Fibrinogen
Prothrombin
TissueFactor
Ca2+
Proaccelerin
Proconvertin
Antihemophilic Factor
Christmas Factor
StuartFactor
Plasma thromboplastinantecedent
Hageman factor
Fibrin Stabilizing Factor

85. Fibrinolysis
Tissueplasminogen
activator
Factor 12 a
kallikrein
Plasminogen Plasmin
Streptokinase
Fibrin
degradation
products
Fibrin
α-2
antiplasmin
Plasminogen
activator
inhibitor - 1
Protein C
Activation
Inhibition

86. Fibrinolytic system
Function:
• Lysisof blood clots
• Clot is destroyed by plasmin
(fibrinolysin) which formed from
plasminogen (profibrinolysin)
• This reaction is activated by blood and
tissueactivators

88. Natural anticoagulant mechanisms
• Prostacyclin (PGI2 ) – Inhibits action of
TXA2 Antithrombin III: – blocks the action
of factors II,IX,X,XI,XII
• Heparin from basophils and mast cells
potentiates effects of antithrombin III
(together they inhibit IX, X, XI, XII and
thrombin)
• Antithromboplastin (inhibits „tissue
factors” – tissue thromboplastins)
• Protein C and S – activated by thrombin;
degrade factor Va and VIIIa

90. Bleeding Disorders
1. Thrombocytopenia - reduced platelet count; generally below
50,000 per cubic millimeter; can cause excessive bleeding from vascular
injury
2. Impaired liver function - lack of procoagulants (clotting factors)
that are made in liver (vitamin K - essential for liver to make clotting
factors for coagulation)
3. Hemophilias - hereditary bleeding disorders that occur almost
exclusively in males
• Hemophilia A - Factor VIII Deficiency – X-linked recessive disorder
(most common)
• Hemophilia B - Factor IX Deficiency - X-linked recessive disorder
• Hemophilia C - Factor XI Deficiency - autosomal recessive disorder seen
primarily in the Ashkenazi Jewish population (can affect women too)