BIO202 Anatomy & Physiology
Lecture Outline Hematology(Blood)
I. Physical Characteristics of Blood:
A. Temperature: approx. 38oC
B. pH: 7.35-7.45
C. Ave. Volume: 5-6 liters (11 pints)
D. Amount/Body Weight: 8% of body weight
E. Composition:
1. 55% Liquid portion
2. 45% Formed elements
II. Soluble Components of Blood:
A. Serum (liquid portion without clotting factors)
B. Plasma (liquid portion + clotting factors)
1. Plasma contains many sorts of proteins including albumins, globulins, clotting factors, complement, regulatory enzymes, as well as electrolytes and hormones.
2. Albumins: most abundant plasma proteins; carriers for many molecules (sterols, bilirubin, hormones, ions...)
3. Globulins: many different types of proteins including immunoglobulins and...
a. alpha1-anti-trypsin (AAT): major globulin; inactivates proteases; important in counteracting endogenous proteolytic activity such as during coagulation, inflammation; AAT-deficency associated with emphysema and liver disease;
b. Haptoglobulin: binds free hemaglobin from lysed RBCs; increases under stress, acute inflammation, infections; decreases with massive hemolysis, burns, transfusion mismatches
c. Transferrin: binds free Fe3+, transports in blood,
III. Blood cells (Formed Elements):All blood cells are produced in red bone marrow
A. Erythrocytes: 4.8-5.4 x 106/mm3; produce about 2.5 million/sec; 120 day lifespan
1. Reticulocytes: immature RBCs (>1%)
2. Hematocrit = % RBC in blood (volume); male = 40-54%; female = 38-46%
3. Anemia: decreased hematocrit; many forms and causes:
a. Iron-deficiency anemia: most common, inadequate iron absorption or excessive excretion
b. Pernicious anemia: lack of intrinsic factor needed for B12 absorption
c. Hemolytic anemia: destruction of RBCs leaving "ghosts"
d. Thalassemia: inherited form of hemolytic anemia - altered form of Hb
e. Aplastic anemia: loss of erythropoesis in red bone marrow
f. Sickle-cell anemia: misshapen RBCs from altered Hb causes poor vascular circulation and hemolysis
E. Polycythemia: increased hematocrit (over 65%); may be spurious or secondary to renal disease
F. Erythropoetin: hormone to stimulate RBC synthesis; given to counteract bone marrow deficits (chemoth.)
G. Erythrocyte and Hemoglobin (Hb) Production and Recycling:
1. Spleen, liver, red bone marrow - macrophage phagocytize damaged/dead RBCs;
globin & heme are separated;
globin digested & amino acids recycled;
2. The Fate of Heme... >a. Fe3+ separated from heme ---> biliverdin ---> bilirubin ---> into blood to liver
b. bilirubin added to bile into small intestine...
c. bilirubin ---> urobilinogen in lrg int. ---> into kidney
(excreted as urobilin) or lrg int. (excreted as stercobilin)
3. The Recycling of Fe3+...
a. Fe3+ bound by transferrin ---> into blood ---> transport to liver...
b. stored in the "F &H Wharehouse" (ferritin & hemosiderin) to be used later...
c. bound again to transferrin ---> into blood to bone marrow for new Hb synthesis.
H. Factors required for RBC synthesis:
1. Fe3+: necessary diet nutrient
2.Vit B12: used for erythropoeisis in red bone marrow
3.Intrinsic factor: produced by stomach parietal cells - aids Vit B12absorption in small intestine
4.Erythropoetin: hypoxia induces kidneys to increase erythropoetin secretion
5.Protein: amino acids used to produce globin
IV. Leukocytes: 5-10,000/mm3
A. Granulocytes:
1.Neutrophils (50-70%); 3 day lifespan; major phagocyte & granulocyte; attracted by inflammatory factors and complement; granules with hydrolytic enzymes; cell dies after degranulation/phagocytosis
a."Band" is immature neutrophil (band-shape nucleus);
b."Seg" is mature neutrophil (segmented nucleus).
c.Neutrophilia: increase %; common with acute bacterial infections
d.Neutropenia: decrease %; common with anemias, viral infections, radiation/chemotherapy;
i)Neutropenia can result in lowered immune protection especially to bacterial/fungal infections.
2.Eosinophils (2-4%); major anti-helminth protection (myelin basic protein released); also contributes to some hypersensitivity reactions and phagocytosis of bacteria.
3.Basophils (<1%); granulocytic, nonphagocytic; major inflammatory cell, releases histamines, proteases and granulocyte-attracting factors.
4.Monocytes (2-8%); only last 8-12 hrs in circ. then migrate to tissue = major function to become macrophage in tissue; play key role in "antigen presentation", express MHC-II.
5. Platelets (thrombocytes) (240-400,000/mm3); crucial to help activate blood clot formation, for platelet plug; spleen acts as reserve site;
6.Lymphocytes (20-30%) mononuclear cells; mediate/regulate specific immune responses (antibody formation, anti- viral and anti-tumor protection)
a.B-cell: produce immunoglobulins (mature in bone marrow)
b.T-cell: activate/regulate B-cells, major immune regulatory cells (mature in thymus)
c.NK cell: natural killer cell; non-specific anti-tumor cytolytic cell
V. Hemostasis:
A.Vascular Spasm:
Smooth muscle contraction - decreases blood flow in damaged vessels
B. Platelet Plug Formation:
Platelet adhesion to exposed collagen
Platelet activation, platelet release reaction,
Platelet aggregation; increased adhesion (via ADP)
C. Coagulation: (all steps require Ca2+)
Stage 1: produce prothrombinase (factors 10/5) via extrinsic and intrisic pathway
Stage 2: produce thrombin, via common pathway
Stage 3: produce fibrin threads
1. Extrinsic Pathway:(initiated by factor outside blood vessels)
Thromboplastin (TF) leaks into blood from tissues
TF ---> 7 ---> 10/5 = prothrombinase
2. Intrisic Pathway: (initiated by factors within blood vessels)
Exposed collagen or basement membrane of endothelial cells initiates pathway
12 ---> 11 ---> 79/8pp ---> 10/5 = prothrombinase
hemophilia A = lack of factor VIII, is sex-linked
hemophilia B = lack of factor IX; is sex-linked
hemophilia C = lack of factor XI; not sex-linked
3. Common Pathway:
Prothrombinase (10/5)*
*prothrombin ---> thrombin **
**fibrinogen is converted to fibrin threads ("CLOT")
**factor XIII activation (fibrin stabilizing factors)
**accelerates prothrombinase (10/5) formation (positive feedback)
**increases platelet activation (positive feedback)
- - fibrin traps & inactivtes thrombin (negative feedback)
VI. Major Blood Group Antigens:
A. ABO Antigens
Isoagglutininglycolipid antigens controlled by various alleles of the I gene (i = nonexpression of I gene)
IAIA or IAi = results in A blood type
IBIBor IBi = results in B blood type
IAIB= results in AB blood type
i i = results in O blood type
Individuals with Type A blood contain antibodies to Type B blood (anti-B antibodies)
Individuals with Type B blood contain antibodies to Type A blood (anti-A antibodies)
Individuals with Type AB blood contain no antibodies to either Type A or Type B blood
Individuals with Type O blood contain antibodies to both Type A or B blood (anti-A and anti-B antibodies)
B. Inheritance of Blood Types
If person with AB blood and O blood have children, a Punnett square illustrates possible offspring blood types:
i / A i / B i
i / A i / B i
This shows 50% offspring will be A i (A blood type) and 50% will be B i (B blood type)
More Examples:
heterozygous B type
heterozygous A type
B / i
A / A B / A i
i / B i / i i
Offspring:
25% AB type
25% A type
25% B type
25% O type / Parents:
homozygous A type
AB type
A / A
A / A A / A A
B / A B / A B
Offspring:
50% A type (homozyg.)
50% AB type / Parents:
heterozygous B type
heterozygous B type
B / i
B / B B / B i
i / B i / i i
Offspring:
25% B type (homozyg.)
50% B type (heterozyg.)
25% O type
C. ABO Compatibility in Blood Transfusions
Individuals with Type A blood contain antibodies to Type B blood (anti-B antibodies)
Individuals with Type B blood contain antibodies to Type A blood (anti-A antibodies)
Individuals with Type AB blood contain no antibodies to either Type A or Type B blood
Individuals with Type O blood contain antibodies to both Type A or B blood (anti-A and anti-B antibodies)
This table summarizes ABO tranfusion compatability:
A / A or AB
B / B or AB
AB / AB only
O / A, B, AB and O
Rh+ / Rh+ only
Rh- / Rh+ or Rh-
/ Recipient blood type: / Can safely receive blood from:
A / A or O
B / B or O
AB / A, B, AB or O
O / O only
Rh+ / Rh+ or Rh-
Rh- / Rh- only
D. Rh Antigen
Rh expression is designated as Rh + (thus A+ blood has expression of A and Rh)
Lack of Rh expression is designated as Rh - (thus B - blood has expression of B but no Rh)
Important for Rh- mother pregnant with Rh+ child
Sensitization of mother during delivery induces high levels of anti-Rh IgG antibodies; (block with Rhogam)
During pregnancy with subsequent Rh+ child, anti-Rh IgG can cross placenta and cause hemolytic disease of newborn (less problem if Rhogam is administered during first delivery)
Transfusions are typically restricted to matching Rh+ donor to Rh+ recipient.
Rh - recipients should not be given Rh+ blood transfusion.
Rh - blood can be transfused into Rh- or Rh+ recipient. (much like O blood can be given to any blood type)
"Universal Donor" = O - "Universal Recipient" = AB +
E. Blood Typing
A small sample of blood is mixed with known reagents containing anti-A, or anti-B or anti-Rh.
A positive reaction is where clumping (agglutination) occurs (antibody binds to RBCs in the blood)
A negative reaction is where no agglutination occurs (antibody does not bind to RBCs)
Severe (life-threatening) mismatch transfusion reactions can occur if donor and recipient do not match ABO type
Check out this Cool Blood-Transfusion Game
This is only a general outline. There is much that has been discussed and presented in lecture that is not included in this outline. All material discussed in lecture is test-material whether or not it is included in this outline.
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