DR. Shaheen Haroon Rashid
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Transcript of DR. Shaheen Haroon Rashid
DR. Shaheen Haroon Rashid
Red Blood Corpuscles (RBCs) DR. Shaheen Haroon Rashid Guyton and
Hall Textbook of Medical Physiology12th ed. (413-420)
At the end of the session the students should be able to: Describe
the structure of RBCs Describe in detail erythropoiesis mechanism
Describe the life-span of RBC (circulation and their breakdown)
Explain the factors affecting erythropoiesis Guyton and Hall
Textbook of Medical Physiology12th ed. ( ) Red blood cells RBCs
Named red blood corpuscles as it not a true cell as it do not
contain nuclei and other cell organells as mitochonderia Normal
RBCs count: Adult male million/ mm3 Adult female 4.5 5 million/ mm3
Being higher in new born and person living at high altitude Normal
RBCs are circular and biconcave discs
RBCs size and shape: Normal RBCs are circular and biconcave discs
Diameter 7.8 micron Thickness 2.5 micron Volume 90 cubic micron
Significance of RBCs shape Larger surface area Allow higher
flexibility that allow RBCs to squeeze in small capillaries RBCs
life span about 120 days Structure of RBCs Like any cell surrounded
by semi-permeablecell membrane Hb is its main content represent
about 33% of RBC volume. Each RBC has 200 million Hb molecules K+
is the main intracellular cation Also contain Carbonic Anhydrase
Enzyme that hydration of CO2 to carbonic acid No mitochondria so
its energy derived from anaerobic glycolysis Erythropoiesis
Erythropoiesis After birth During fetal life Def: formation of
RBCs
Sites of erythropoiesis After birth During fetal life Active (red)
BM: In infancy & childhood red BM present nearly in all bones
In adult red BM is restricted in ends of long bones, vertebrae,
ribs, sternum, skull, pelvic bones 1) Yolk sac: in the first 6 w 2)
Liver & spleen: from 6 w 6 m 3) Bone marrow BM: from 6 m until
after birth Stages of haematopoiesis Stages of Eythropoiesis
PHSC developed under the effect of growth factor IL-3 to committed
stem cell which then developed to CFU-E under the effect of
erythropoietin CFU-E then developed to proerythroblast then to
erythroblasts (basophil, polychromatophil, orthochromatic)
Erythroblasts give normoblasts which lose their nucleus, and
endoplasmic reticulum and transformed into reticulocytes which then
become mature RBCs Reticulocytes represent less than 1% of RBCs in
peripheral blood Stages of Eythropoiesis Factors affecting
erythropoiesis
O2 supply to the tissue = role of erythropoietin Nutritional
factors: Dietary protein content Mineral ions Iorn Copper Cobalt
Vitamins: vit B12. folic acid, and others Hormonal factors State of
bone marrow State of liver 1) Tissue oxygenation &
erythropoietin
Decrease O2 supply to the tissue (Hypoxia) is the primary stimulus
for erythropoiesis as in: Anaemia High altitudes Lung diseases
Cyanotic heart diseases Hypoxia stimulate erythropoietin secretion
that stimulate eythropoiesis in bone marrow Erythropoietin A
glycoprotein hormone (mw 34000 d) Source: Function:
90% from the kidney (renal tubular epithelium or endothelial cells
of peritubular capillaries) and 10% form the liver (but mainly from
the liver in fetal life). Function: Stimulates the production of
proerythroblasts from stem cells Speeds up all stages of
development of erythroblasts into mature RBCs Regulation (control
of secretion): Hypoxia the main stimulus Adrenaline, noradernaline
and some PGs Androgens Adenosine (adenosine antagonist decrease EPO
secretion) Cobalt salts Clinical uses: Chronic renal failure
Aplastic anaemia Anaemia with chronic diseases Erythropoietin
Mechanism
Imbalance Start Normal blood oxygen levels Stimulus: Hypoxia due to
decreased RBC count, decreased availability of O2 to blood, or
increased tissue demands for O2 Imbalance IncreasesO2-carrying
ability of blood Reduces O2 levels in blood 90% of EPO is renal
Erythropoietin stimulates red bone marrow Kidney (and liver to a
smaller extent) releases erythropoietin Enhanced erythropoiesis
increases RBC count 2) Dietary factors A) proteins:
Proteins of high biological value are essential for erythropoeisis
(for the formation of globin part of Hb. Prolonged protein under
nutrition lead to anaemia B) Minerals: Iron (Fe) is essential for
formation of haeme part of Hb. Copper (Cu) Cu essential for
erythropoeisis, transported in the plasma by ceruloplasmin (which
catalyze the oxidation of ferrous iron to ferric) Co-factors in Hb
synthesis Cobalt (Co) Stimulate erythropoeisis though stimulation
of erythropoeitin secretion from the kdney enters in synthesis of
Vit. B12 C) Vitamins: Vit B12, folic acid, others vit C Vitamin B12
& Folic acid; essential for DNA synthesis & maturation of
bone marrow cells Iron (Fe+2) Iron metabolism: Daily
requirement:
Iron is essential for formation of haeme part of Hb (also in other
heme containing particles as myoglbin, cytochrome oxidase,
catalase,perioxidase) decrease iron supply leads to iron deficiency
anaemia Iron metabolism: The total body iron content is 4 5 gm. 65%
in Hb, 15-30% stored as ferritin in RES in the liver, 4% in
myoglobin, 1% in enzymes, 0.1% in transferrin in plasma. Normal
serum iron level. ( ug/dL) is bound to Transferrin Daily
requirement: 0.6 mg / day for male 1.3 mg /day for female
Absorption of Iron Iron actively transported mainly in the upper
small intestine (Duodenum & Jejunum) 1) Dietary Ferric (Fe3+)
reduced to ferrous (Fe2+) 2) Fe2+ or Heme transported at brush
border by different carrier proteins (IT, iron transporter &
HT, heme transporter) 3) Intracellularly Fe2+ released from Heme by
heme oxygenase Most of intracellular Fe2+ actively transported (AT)
across the basolateral membrane to enter the blood. Some Fe2+
oxidize to Fe3+ & bound apoferritin forming ferritin Decrease
Fe2+ Absorption Increase Fe2+ Absorption Oxalates & Phosphates
Phytates & Tannin Vit C Gastric HCl Iron absorption occurs
according to body needs when all apoferritin become saturated iron
absorption from enterocytes is inhibited Transport: In blood Fe2+
oxidize to Fe3+ & bound apotransferrin forming transferrin
reach various iron tissues store. Storage: Excess iron in blood is
stored in cells of RE system (liver mainly and spleen) it combind
with apoferritin forming tissue ferritin Feedback regulation of
iron absorption
The rate of iron absorption from GIT depend on the iron stores in
the body: increased 5 times or more when iron stores in the body
become depleted Greatly decrease when the body iron stores are
saturated in the form of ferritin due to: The transferrin become
fully saturated with iron (decrease the iron binding capacity of
the blood) that leads to accumulation of ferritin in enterocytes
that depress the active absorption of iron from the intestinal
lumen The liver decrease the synthesis of apotransferrin required
for iron absorption. Iron Transport & Metabolism III- Dietary
vitamins Vitamin B12 & Folic acid; essential for DNA synthesis
& maturation of bone marrow cells (maturation factors).
Deficiency of B12 & Folic acid leads to failure of maturation
of erythroblasts leading to formation of fragile larger cells with
shorter life span (Macrocytic or Megaloblastic anaemia) Vit B12
Source: animal source liver, meat, egg, fish, vegetables are poor
for vit B12 Daily requirement: 5 g. Absorption: Vit B12 combined
with intrinsic factor (a glycoprotein secreted by parietal cells of
gastric gland Intrinsic factor-vit B12 complex absorbed in the
terminal ileum by pinocytosis Transport: Vit B12 is carried in the
blood by PP transcobalamin to the site of storage or use Storage:
Liver store large quantities of vit B12 (5 mg) that sufficient to
supply vit B12 requirement for about 3 years Vit B12 deficiency:
Megaloblastic anaemia Neurological manifestations III- Role of
Liver Healthy Liver is essential for normal erythropoiesis as it
the site for: Storage of Vit. B12 & iron synthesis of 10% of
EPO Chronic liver disease leads to anaemia IV- Hormones Thyroid H
Glucocorticoides Androgens
All stimulate Erythropoiesis as they promote tissue metabolism V-
State of bone marrow Healthy bone marrow is essential for normal
erythropoiesis Destruction of BM by irradiation, drugs toxins leads
to aplastic anaemia Life Cycle of Red Blood Cells Life span and
fate of RBCs:
Erythrocytes live in the circulation for an average of 120 days. *
As the cells grow older, they become more fragile and rupture
during their passage through narrow spots in the circulation
specially in the spleen. * The released Hb from ruptured RBCs is
phagocytized by the macrophage cells. * Inside the macrophage
cells: Hb breaks into globin + heme. Globin amino acids Heme iron +
biliverdin bilirubin biliruin (yellow, pigment excreted by the
liver in bile).