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# FUNDAMENTALS OF MEDICAL PHYSIOLOGY

90.103

## Chapter 11: BLOOD and BLOOD ELEMENTS

Office: R3040, St. Boniface Research Centre
tel: 235-3507
e-mail: peterz@sbrc.umanitoba.ca

Section Outline:

## 6. Hemostasis the process by which bleeding is stopped after injury

7. Clotting Factors a look at the proteolytic cascade that results in clot formation

Objectives:

## 1. Understand the function of blood and its components

2. Calculate hematocrit

## 6. Correlate erythrocyte shape to function; understand the characteristics of hemoglobin as

they relate to red cell function
7. Recount the various red cell disorders

## 12. Understand clot formation and its associated disorders

Figures and Tables Applicable to the Lecture:

Table 11-1, Figure 11-1, Figure 11-8, Figure 11-9, Figure 11-12

Lecture Material:

1. Blood

1.1 Function: to transport materials between cells and the external environment.

1.2 Components: plasma, erythrocytes (red blood cells), leukocytes (white blood cells),
platelets.

## 1.3 Amount: men - 5.5 litres

women - 5 litres

1.4 Composition: 42-45% erythrocytes, 55-58% plasma, <1% leukocytes and platelets

1.4.1 Hematocrit: The number of erythrocytes in blood expressed as a per cent of total blood
volume. The "crit" in physician-speak.

1.4.1.1 Method: Take sample of heparinized blood (heparin treatment prevents clotting) and
place into glass centrifuge tube. Spin in centrifuge at 5000 rpm for 5
minutes. Determine total volume of sample (in millilitres). Determine total
volume of erythrocytes in the sample (in millilitres). Calculate hematocrit
using the formula:
hematocrit = ([volume of erythrocytes (mL)]/[volume of blood (mL)])H100.

## Refer to Figure 11-1: Hematocrit

2. Plasma

2.1 Function: i) to carry and distribute various molecules around the body
ii) to absorb and distribute heat
iii) to transport proteins

## 2.2 Components: i) water (~90%)

ii) electrolytes (Na+, Cl-, HCO3, K+, Ca2+)
iii) nutrients (glucose, amino acids, fats, vitamins)
iv) gases (CO2); important for acid-base balance
v) hormones
vi) wastes (urea, creatinine)
vii) plasma proteins

## 2.2.1 Plasma proteins

2.2.1.1 Functions: i) maintain osmotic pressure in capillaries to avoid fluid loss (general)
ii) act as buffers to maintain blood pH (general)
iii)assist transport of water insoluble compounds
iv)blood clotting factors
v) protection
2.2.1.2 Components: i) albumins (osmotic pressure, transport)
ii) á/â-globulins (clotting factors, transport)
iii) ã-globulins (immunoglobulins for body's defenses)
iv) fibrinogen (blood clotting)

3. Erythrocytes

## 3.1 Function: oxygen transport (accomplished by 5 billion cells per millilitre)

3.2 Properties: i) biconcave shape that provides large surface area for O2 diffusion
ii) membrane flexibility for movement through capillaries
iii) lack of nucleus and other major cellular organelles (eg. mitochomdria)
iv) glycolytic enzymes (for energy production in absence of mitochondria)
v) carbonic anhydrase (converts CO2 to bicarbonate for transport)
vi) hemoglobin

3.3 Hemoglobin: The oxygen carrier in red blood cells that gives them their red colour. There
are over 100 million molecules per erythrocyte.

3.3.1 Structure: i) 4 polypeptide chains that associate to form the "globin" component
ii) each polypeptide chain includes one iron-containing heme group

3.3.2 Mechanism: each heme group binds one molecule of oxygen (4 O2 per hemoglobin)
3.3.3 Other Properties: i) carries a small portion of blood CO2
ii) helps to buffer blood
iii) binds strongly to carbon monoxide (can displace O2)

3.4 Erythropoeisis: The life span of a red blood cell is about 120 days. Dead cells are removed
by the spleen. Without the necessary organelles, they cannot repair
themselves or divide. New cells are produced in the bone marrow by a
process called erythropoiesis. Stem cells in the marrow (usually called
undifferentiated pluripotent stem cells because they have no defined cellular
characteristics and they continue to produce new cells) divide to form cells
that can differentiate (i.e. change their properties) into red blood cells over a
period that involves 13 cell divisions. The intermediate cells retain their
organelles and can still divide. Because they have a nucleus, these immature
red blood cells are often termed reticulocytes.

3.4.1 Regulation: Erythropoeisis is controlled by factors that monitor oxygen levels in the
body. These sensors are present in the kidney. When low O2 levels are
detected (implying decreased atmospheric O2 - eg. high elevations - or
reduced erythrocyte numbers), the kidney releases a hormone called
erythropoietin. This factor stimulates the pluripotent stem cells in the bone
marrow to increase erythrocyte production. If demand is great, some
reticulocytes will be released into the blood. Their presence is indicative of
rapid erythrocyte production and can predict a disorder like anemia.

## 3.5 Disorders: anemia, polycytheia

3.5.1 Anemia: a reduced number of erythrocytes that leads to an inadequate supply of oxygen to
the body tissues; indicated by hematocrit of <35%
3.5.1.1 Nutritional: dietary deficiencies of iron and folic acid (B vitamin) reduce the rate of
erthropoeisis because they are required for either formation of hemoglobin
(iron) or cell growth and division
3.5.1.2 Pernicious: lack of vitamin B 12, a factor necessary for folic acid regeneration within cells
3.5.1.3 Aplastic: reduced capacity of bone marrow to produce red blood cells because of
damage to this tissue by chemicals, radiation or invasion by cancer cells
3.5.1.4 Renal: kidney disease that reduces erythropoeitin production
3.5.1.5 Hemorrhagic: excessive loss of blood; recovery occurs once cells are manufactured after
blood loss or through transfusion
3.5.1.6 Hemolytic: damage to red blood cells leading to their rupture (termed hemolysis); eg.
sickle cell anemia (genetic condition affecting cell shape) or malaria, a
protozoan infection that causes cells to hemolyze prematurely
3.5.2 Polycytheia excess numbers of red blood cells
3.5.2.1 Primary: cancer-like condition of uncontrolled erythrocyte production leading to
severe hematocrits of >70%; resulting increase in blood viscosity increases
cardiac load and peripheral resistance (producing high blood pressure) and
can reduce oxygen delivery
3.5.2.2 Secondary: normal process that occurs upon change in available oxygen; occurs most
frequently when going from low to high elevation
3.5.2.3 Dehydration: loss of fluid due to decreased water intake or excessive water loss results in
elevated hematocrit; there is no change in erytrocyte number, just a decrease
in blood plasma component

4. Leukocytes

## 4.1 Function: i) defend against pathogens (infection)

ii) identify and destroy cancer cells
iii) remove cellular debris (tissue repair)

4.2 Properties: circulate around the body within the blood and exit through the vessel wall
in regions of tissue damage (physical or infectious)

## 4.3 Amounts: 1 leukocyte per 700 erythrocytes

4.4 Source: primarily produced from the same stem cells present in the bone marrow
that produce erythrocytes; lymphocytes are made in lymph nodes and tonsils
as an individual ages

## 4.5 Types: i) polymorphonuclear granulocytes (neutrophil, eosinophil, basophil)

ii) mononuclear agranulocytes (monocyte, lymphocyte)

## 4.5.1 Neutrophils: important in fighting bacterial infections; operate by phagocytosis

4.5.2 Eosinophils: associated with allergic reactions and parasite infectations; operate by
binding to target and secreting toxins that kill the target

## 4.5.3 Basophils: release histamine during allergic reaction and heparin

4.5.4 Monocytes: enter various tissues and differentiate into macrophages which opreate by
phagocytosis

## 4.5.5 Lymphocytes: B lymphocytes produce antibodies; T lymphocytes specifically bind to their

targets and kill them

## 4.6 Disorders: infectious mononucleosis, leukemia, immunosuppression

4.6.1 Mononucleosis: infection by Epstein-Barr virus that elevates circulating lymphocytes

## 4.6.2 Leukemia: cancer that is characterized by uncontrolled proliferation of leukocytes

4.6.3 Immunosuppression: caused by contact with radiation or chemicals that reduce bone
marrow capacity to produce leukocytes; ability of body to defend
against infection is compromised

5. Platelets

## 5.2 Properties: small cellular fragments of megakaryocytes (present in bone marrow)

containing actin and myosin for contraction and storage granules for
regulatory chemicals

## 5.3 Mechanism: i) platelets circulate in blood

ii) a break in the endothelial lining of a blood vessel allows platelets to attach to
underlying collagen fibres
iv) nearby platelets become "sticky" and these adhere to the platelets already
present
v) a platelet plug forms around the break
vi) prostacyclin is released from intact endothelium prevents expansion of plug
to adjacent areas that are not damaged
vii) serotonin, epinephrine and thromboxane A2 are also released from the
platelets and stimulate constriction of the vessel
viii) platelet constriction strengthens the plug
ix) platelets release chemicals that enhance blood coagulation

6. Hemostasis

## 6.3 Steps: i) vascular spasm

ii) formation of a platelet plug
iii) clotting of the blood (or coagulation)

6.3.1 Spasm: vasoconstriction in response to damage decreases the size of the wound and
in this way reduces the rate of blood loss
6.3.2 Platelets: see section 5

6.3.3 Coagulation: transformation of fluid blood into a solid gel at a break in the blood vessel

7. Clotting Factors

7.1 Function: clotting factors consist of a number of distinct proteins and enzymes that
operate collectively to form a blot clot

7.2 Components:
i) fibrinogen; precursor of fibrin, an insoluble protein that makes up most of
the clot
ii) thrombin; the enzyme that converts fibrinogen to fibrin at the site of injury
iii) factor XIII the fibrin stabilizing factor also activated by thrombin that cross-
links fibrin molecules and thus strengthens the clot
iv) factor X; the last component of the clotting cascade; its function is to activate
thrombin from prothrombin
v) PF3 (platelet factor 3); a stimulator of the clotting cascade that is secreted by
platelets

7.3 Clotting Cascade: a series of sequential steps that result in the conversion of factors from their
inactive to their active state

7.3.1 Intrinsic Cascade: i) factor XII (Hageman factor) is activated upon contact with exposed
collagen fibres after a vessel is damaged
ii) factor XII activates factor XI
iii) factor XI activates factor IX (factor IV is also required)
iv) factor IX activates factor X (factor VIII is also required)
v) factor X activates prothrombin (factor V is also required)
vi) thrombin converts fibrinogen to fibrn
vii) fibrin forms the clot (factor XIII assists this process)

## 7.3.2 Extrinsic Cascade: i) damaged tissue releases thromboplastin

ii) thromboplastin activates factor X
iii) factor X activates prothrombin
iv) thrombin converts fibrinogen to fibrin
v) fibrin forms the clot

## Refer to Figure 11-12: Clot pathways

7.3.3 Key Words: each clotting factor is a protease that functions by cleaving an
inactive protein (or zymogen) into its active form
7.3.4 Reasons: i) such an extensive system of individual steps is important for ensuring
coagulation does not occur unless it is needed; for example, clotting
that occurs at the site of a vessel damaged by atherosclerosis can lead
to a heart attack; this damage is real, but not the type of damage that
requires clot formation; this is also why acetylsalicylic acid (ASA,
aspirin) can successfully prevent heart attacks - ASA inhibits blood
clotting by blocking platelet aggregation
ii) amplification can occur at each step of the cascade, so that billions of
fibrin molecules are produced rapidly enough to prevent severe loss
of blood

7.4 Clot Removal: i) during the subsequent healing process in which new tissue is
produced to repair the damaged region, the clot is dissolved through
the action of plasmin; plasmin is formed from its inactive precursor,
plasminogen, by factor XII
ii) fibrin is occasionally produced in healthy vessels; to prevent the
formation of a clot, the fibrin is degraded by tissue plasminogen
activator (tPA); this protein is now used clinically to dissolve blood
clots that cause heart attacks

## 7.5 Disorders: i) thromboembolism is the result of inappropriate clot formation; it combines

two words, thrombus for a clot attached to a vessel wall, and
emboli, a free floating clot
ii) septicemic shock is widespread clotting that occurs when infectious
bacteria release toxins that initiate the clotting cascade
iii) hemophilia is the inability to form a clot and results in death from
blood loss; this is a genetic condition that can arise from a deficiency
in any one of the many clotting factors needed to form a clot
iv) thrombocytopenia purpura is the name given to a condition in which
an individual develops many small purple blotches; these arise from
the many small ruptures in capillaries and small vessels due to
normal activities; the blotches are caused by excessive bleeding at
these sites due to a lack of platelets which normally seal the breaks
before much blood leaks out
v) vitamin deficiency, particularly vitamin K, can also cause a bleeding
tendency; vitamin K is required for prothrombin synthesis by the
liver