Blood

Dr Intesar Burney
Professor physiology department
Sir Syed university of medical and dental sciences
Karachi

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 Learning objective
• Define blood, describe its general properties and
function.
• Discuss blood plasma and its constituents.
• Explain the mechanism od development of blood cells.
• Describe the structure and life cycle of RBCs.
• Classify Leukocytes and discuss its functions.
• Define Hemostasis and explain the three mechanism that
contribute hemostasis
• Describe ABO blood groups and Rh factor.

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 Blood
The type of connective tissue which is reddish in color and
consists of plasma and formed elements flowing inside the
closed vessels is called blood.
General properties of blood:
• Mean fraction of body weight 8%
• Mean temperature 38C
• Volume in adult body F 4-5 L, M 5-6 L
• PH 7.35-7.45
• Viscosity (relative to water) 4.5-5.5
• Salinity 0.9%
• Sp. Gravity 1.057

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 Function of blood
1.Transportation
– oxygen and carbon dioxide
– food molecules (glucose, lipids, amino acids)
– ions (e.g., Na+, Ca2+, HCO3−)
– wastes (e.g., urea)
– hormones
2.Regulation
– Body temperature
– PH
3.Protection
– Clotting
– WBCS defense
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 Plasma
• yellowish clear liquid, composed of water, proteins and other
solutes.
• Water = 91%
• Proteins = 7% (all synthesized by the liver)
• Albumin = 54%, regulates osmotic pressure
• Globulins = 38%, alpha and beta globulins in transport,
• gamma globulins in defense (antibodies)
• Fibrinogen = 7%, coagulation
• Other solutes =2%
• Electrolytes - Na+, K+, Ca++, Mg++
• Nutrients - glucose, amino acids, fatty acids, monoglycerides ...
• Gases - O2, N2, CO2
• Regulatory substance - hormones, enzymes
• Vitamins
• Wastes

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 Formed elements
• Formed from precursor cells or stem cells
(hemocytoblast) located in bone marrow
• formed elements
• =>red blood cells or erythrocytes- not
true cells
• =>white blood cells or leukocytes
• =>platelets or thrombocytes- not true
cells
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 7.8 µm in diameter & 2.5 µm thick

nt:
Red4.7-5.2
blood cells (erythrocytes)
million per mm3 of blood

Not present

duction: Bone marrow

120 days

truction: liver and spleen

Oxygen transport

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 Production of blood cells

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Production and Maturation of
Red Blood Cells

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• Hormone, erythropoietin:
• Erythropoietin is a substance produced by the
kidney that leads to the formation of red blood
cells in the bone marrow. Abbreviated: EPO.
• The kidney cells that make EPO are
specialized and are sensitive to low oxygen
levels in the blood coming into the kidney.
These cells release erythropoietin when the
oxygen level is low in the kidney

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• Erythropoietin stimulates the bone marrow to
produce more red blood cells which in turn
increases the oxygen-carrying capacity of the
blood.
• EPO is the prime regulator of red cell
production. Its major functions are to promote
the differentiation and development of red
blood cells and to initiate the production of
hemoglobin, the molecule within red cells that
transports oxygen.

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• EPO is produced not only in the kidney but
also, to a lesser extent, in the liver. The EPO
gene has been found on human chromosome 7
(in band 7q21). Different DNA sequences
flanking the EPO gene act to control liver
versus kidney production of EPO.
• The measurement of EPO in the blood can
indicate bone marrow disorders or kidney
disease.

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• Normal levels of EPO are 0 to 19 mU/ml
(milliunits per milliliter). Elevated levels can
be seen in polycythemia, a disorder
characterized by an excess of red blood cells.
Lower than normal values of EPO are seen in
chronic renal failure.
• Using recombinant DNA technology, EPO has
been synthetically produced for use in persons
with certain types of anemia: anemia due to
kidney failure, anemia secondary to AZT
treatment of AIDS , and anemia associated
with cancer.
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• EPO has been much misused as a performance-
enhancing drug in endurance athletes such as
reportedly cyclists (in the Tour de France), long-
distance runners, speed skaters, and Nordic (cross-
country) skiers. When misused in such situations,
EPO is thought to be especially dangerous
(perhaps because dehydration can further increase
the viscosity of the blood, increasing the risk for
heart attacks and strokes. EPO has been banned by
the Tour, the Olympics, and other sports
organizations

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 Structure of Erythrocyte
• Each erythrocyte contain 280 million hemoglobin molecule,
which give blood its red color.
• Hemoglobin molecule contain 4 protein chains called globins,
each of which is bound to 1 heme.
• The iron group of heme is able to combine with oxygen in the
lung and release oxygen in the tissue.

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Chemical steps in the formation of hemoglobin:
1.2 succinyl-CoA + 2 glycine → pyrrole
2.4 pyrrole → protoporphyrine IX
3.protoporphyrine IX + Fe+ → heme
4.heme + polypeptide → hemoglobin chains
5.2 α chains + 2 β chains → hemoglobine A

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Types of hemoglobin:
•Hemoglobin A (α2, β2 chains)
•Hemoglobin AIC (has a glucose attached to the terminal
amino acid valine in each β chain, it increases in the
blood of people who suffer from diabetes mellitus)
•Hemoglobin A2 (instead of 2 β chains, there are 2 δ
chains) Hemoglobin A2 (HbA2) is a normal variant of
hemoglobin A that consists of two alpha and two delta
chains (α2δ2) and is found in small quantity in normal
human blood. Hemoglobin A2 may be increased in beta
thalassemia or to people who are heterozygous to beta
thalassemia gene
•Hemoglobin F (in the fetus, 2 α chains and 2 γ chains)
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• Most of the α-thalassemias are caused by deletions
that remove one or more of the α-globin gene loci.
• The severity of the disease that results from these
lesions is directly proportional to the number of α-
globin genes that are missing
• For example, the loss of a single α-globin gene is
associated with a silent-carrier state, whereas the
deletion of all four α-globin genes is associated with
fetal death in utero, because the blood has virtually no
oxygen-delivering capacity.
• With loss of three α-globin genes there is a relative
excess of β-globin or chains other than α-globin (TM)

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Binding of hemoglobin to oxygen:
•hemoglobin composed of 4 polypeptide chains
(represented in this diagram by different colors.
• Each chain contains one heme group each of
which contains one iron ion.
• The iron is the site of oxygen binding; each
iron can bind one O2 molecule thus each
hemoglobin molecule is capable of binding a
total to four (4) O2 molecules.

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Iron metabolism:

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1.Iron (Ferric) from foods is ingested.
2.To be absorbed by the intestinal cells, ferric ions (Fe +3)
must be reduced to ferrous ions (Fe+2) by agents like
Vitamin C (ascorbate).
3.Ferrous ions (Fe+2) are bound to apoferritin then
oxidized to ferric ions (Fe+3) by ceruloplasmin to
become bound as ferritin.
4. Ferritin is carried into blood (plasma) and releases its
ferric ions (Fe+3). 2 ferric ions (Fe+3) are then absorbed by the
protein apotransferrin to become transferrin.
5.Ferric (Fe+3) ions are then incorporated into the bone
marrow for hemoglobin production.
6. RBC’s are degraded by the spleen, liver and macrophages.
Iron leftovers from RBC’s are carried by transferrin and
recycled.
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 Life Cycle of RBC
• Macrophage in spleen & liver, phagocytize RBC & split
heme & globin
• Globin broken into amino acids to be reused
• Fe removed from heme & attaches to transferrin
• Fe-transferrin → red marrow → Hb synthesis
• Erythropoiesis in red marrow
• Fe removed from heme → non-Fe portion → biliverdin
→bilirubin →bile → GI tract
• Bilirubin →urobilinogen in large intestine →some
urobilinogen →blood →in kidney urobilin → yellow
pigment in urine
• Most urobilinogen → feces → as brown pigment
stercobilin

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Definition of Anemia
 Deficiency in the oxygen-carrying capacity
of the blood due to a diminished
erythrocyte mass.
 May be due to:
 Erythrocyte loss (bleeding)
 Decreased Erythrocyte production
 low erythropoietin
 Decreased marrow response to erythropoietin
 Increased Erythrocyte destruction
(hemolysis)
Measurements of Anemia
 Hemoglobin = grams of hemoglobin per 100 mL of
whole blood (g/dL)
 Hematocrit = percent of a sample of whole blood
occupied by intact red blood cells
 RBC = millions of red blood cells per microL of whole
blood
 MCV = Mean corpuscular volume
 If > 100 → Macrocytic anemia
 If 80 – 100 → Normocytic anemia
 If < 80 → Microcytic anemia
Laboratory Definition of Anemia
 Hgb:
 Women: <12.0
 Men: < 13.5
 Hct:
 Women: < 36
 Men: <41
Symptoms of Anemia
 Decreased oxygenation
 Exertional dyspnea
 Dyspnea at rest
 Fatigue
 Bounding pulses
 Lethargy, confusion
 Decreased volume
 Fatigue
 Muscle cramps
 Postural dizziness
 syncope
Causes of Anemia --
Erythrocyte Loss
 Bleeding
 Chronic (gastrointestinal, menstrual)
 Acute/Hemodynamically significant:
 Gastrointestinal
 Retroperitoneal
Anemia due to
Low Erythropoietin
 Kidney Disease
 Normochromic, normocytic
 Low reticulocyte count
 Frequently, peripheral smear in uremic
patients show “burr cells” or echinocytes
 Target hemoglobin for patients on
dialysis is 11 to 12 g/dL
 Administer erythropoietin or darbopoietin
weekly
 Good Iron stores must be maintained
Types of Anenia

 Iron-Deficiency
 Vitamin B12 Deficiency
 Folate Deficiency
 Anemia of Chronic Disease
Iron Deficiency

 Can result from:

 Pregnancy/lactation
 Normal growth
 Blood loss
 Intravascular hemolysis
 Gastric bypass
 Malabsorption
 Iron is absorbed in proximal small bowel; decreased
abosrption in celiac disease, inflammatory bowel
disease
 Tendency to eat ice, clay, starch, crunchy materials
 May have pallor, koilonychia of the nails, beeturia
 Peripheral smear shows microcytic, hypochromic
red cells with marked anisopoikilocytosis.
Iron Deficiency Anemia
Iron Deficiency Anemia -
koilonychia
Iron Deficiency Anemia – Lab
Findings
 Serum Iron
 LOW (< 60 micrograms/dL)
 Total Iron Binding Capacity (TIBC)
 HIGH ( > 360 micrograms/dL)
 Serum Ferritin
 LOW (< 20 nanograms/mL)
 Can be “falsely”normal in inflammatory
states
Treatment of Iron Deficiency
Anemia
 Oral iron salts
 Ferrous sulfate – 325 mg po Q Day
 Side effects: constipation, black stools,
positive hemmoccult test
 Vitamin C can facilitate iron absorption.
Cobalamin (Vitamin B12) Deficiency

 Macrocytic anemia
 Lab Values
 Cobalamin level < 200 pg/mL
 Elevated serum methylmalonic acid
 Elevated serum homocysteine
 Vit. B12 is needed for DNA synthesis
 Binds to intrinsic factor in the small bowel in order to be
absorbed
 Pernicious anemia: antibodies to intrinsic factor
 Diagnosed by checking antibody levels (rather than Schilling
test)
 Deficiency can result in neuropsychiatric symptoms
 Spastic ataxia, psychosis, loss of vibratory sense, dementia
 Frequently not reversible with cobalamin replacement
 Smear shows macrocytosis with hypersegmentation of
polymorphonuclear cells, with possible basophilic stippling.
Vitamin B12 Deficiency
Treatment of Vitamin B12
Deficiency
 Vitamin B12 – 1000 micrograms intramuscularly
monthly
-OR-
 Vitamin B12 – 1000-2000 micrograms po QDaily
Folate Deficiency
 Macrocytic anemia
 Lab Values
 Low folate
 Increased serum homocystine
 NORMAL methylmalonic acid
 Often occurs with decreased oral intake, increased utilization,
or impaired absorption of folate
 Folate is normally absorbed in duodenum and proximal jejunum –
deficiency found in celiac disease, regional enteritis,
amyloidosis
 Deficiency frequently in alcoholics, because enzyme required for
deglutamation of folate is inhibited by alcohol.
 Deficiency often found in pregnant women, persons with
desquamating skin disorders, patients with sickle cell
anemia (and other conditions associated with rapid cell division
and turnover)
 Smear shows macrocytosis with hypersegmented neutrophils
Folate Deficiency
 Polycythemia, or erythrocytosis, as it is
sometimes referred to, denotes an increase in
the blood concentration of red cells, which
usually correlates with an increase in the
hemoglobin concentration.
 Polycythemia may be relative, when there is
hemoconcentration caused by a decrease in
plasma volume, or absolute, when there is an
increase in the total red cell mass.
 Causes of Relative polycythemia:
Relative polycythemia results from any cause of
dehydration, such as water deprivation,
prolonged vomiting, diarrhea, or the excessive
use of diuretics.
 Causes of Absolute polycythemia:
Absolute polycythemia is said to be primary
when the increase in red cell mass results
from an autonomous proliferation of the
myeloid stem cells, and secondary when the
red cell progenitors are proliferating in
response to an increase in erythropoietin
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