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BLOOD
ā€¢ Your body has over 160,000 km (100,000
miles) of blood vessels. which if laid end to
end, would stretch 2 and a half times around
the Earth.
ā€¢ There are four main blood cell types, A, B, AB,
and O. Each can be positive or Negative. AB is
the Universal recipient while O negative is the
universal donor.
ā€¢ In an average life time the human heart
pumps 1.5 million barrels of blood (that's
enough to fill 200 train tank cars).
One unit of blood can be separated into several
components: red blood cells, plasma, platelets and
cryoprecipitate.
Pregnant women have roughly 50% more blood by
week 20 of pregnancy than they did before conception
ā€¢ In emergencies, coconut water can be used as
a substitute for blood plasma.
ā€¢ A blood cell can make a complete circuit of
your body in less than 30 seconds.
There are about .2 mg of gold in your blood
stream
Your blood accounts for 8% of your body weight
ā€¢ Mosquitoes prefer people with blood type "Oā€œ
ā€¢ Every year, the average meat eating American
ingests enough blood to fill a can of soda
ā€¢ Those strange bright white dots you see
floating around when you look at the sky are
white blood cells (it's called blue field entoptic
phenomenon)
ā€¢ George Washington was bled to death by
doctors. This is because bloodletting was a
common practice back then. It was supposed
to get rid of "bad blood"
ā€¢ A newborn baby has about one cup of blood
in his body
ā€¢ 2. Not every animal has red blood. Spiders,
lobsters and snails have blue blood due to the
presence of the protein haemocyanin which
contains copper.
ā€¢ The amount of blood in a pregnant woman's
body will have increased by 50% by the 20th
week of pregnancy.
ā€¢ Some Japanese people believe that blood
type is an indicator of a personā€™s personality.
There are even novelty goods themed after
blood types.
ā€¢ . Nothing is left to chance for the President of the
United States. The Presidential car stores the
President's blood type in the boot of the car just
in case of emergencies.
ā€¢ Research has shown that mosquitoes prefer
blood type O. It would take 1,200,000
mosquitoes, each sucking once, to totally drain a
human of blood.
ā€¢ Larger animals have slower heart rates than
smaller animals. This means that the blood in
their body takes longer to circulate around.
For example, a blue whaleā€™s heart only beats 5
times per minute while humans beat closer to
75 per minute.
ā€¢ There has been an example of blood
becoming a dark green colour. Surgeons
operating on a 42-year-old Canadian man got
a shock when they discovered dark green
blood coursing through his arteries, like Star
Trekā€˜s Mr Spock. It's thought this was caused
by of a type of migraine medication.
ā€¢
ā€¢ Ancient Egyptians believed that wine was the
blood of people who dared to battle against
Gods. The reason why they believed this is
that drinking wine temporarily made people
crazy and drove them out of their senses. This
is precisely why ancient Egyptians avoided
drinking wine.
BODY FLUIDS
ā€¢ WATER INTOXICATION OR OVERHYDRATION
ā€¢ Definition
ā€¢ Water intoxication is the condition
characterized by great increase in the water
content of the body. It is also called
overhydration, hyperhydration, water excess
or water poisoning.
ā€¢ But there are some conditions that can produce water
intoxication.
ā€¢ 1. Heart failure in which heart cannot pump blood
properly
ā€¢ 2. Renal disorders in which kidney fails to excrete
enough water in urine
ā€¢ 3. Hypersecretion of antidiuretic hormone as in the
case of syndrome of inappropriate hypersecretion
of antidiuretic hormone (SIADH)
ā€¢ 4. Intravenous administration of unduly large amount of
medications and fluids than the personā€™s body can excrete
ā€¢ Infants have greater risk of developing water
intoxication in the first month of life, when the
filtration mechanism of the kidney is
underdeveloped and cannot excrete the fluid
rapidly
ā€¢ 6. Water intoxication is also common in children
having swimming practice, since they are more
prone to drink too much of water while
swimming
ā€¢ 7. An adult (whose heart and kidneys are
functioning normally) can develop water
intoxication, if the person consumes about 8 L of
water everyday regularly.
ā€¢ Signs and Symptoms
ā€¢ 1. Since the brain is more vulnerable to the effects of
ā€¢ water intoxication, behavioral changes appear first
ā€¢ 2. Person becomes drowsy and inattentive
ā€¢ 3. Nausea and vomiting occur
ā€¢ 4. There is sudden loss of weight, followed by
weakness
ā€¢ and blurred vision
ā€¢ 5. Anemia, acidosis, cyanosis, hemorrhage and shock
ā€¢ are also common
ā€¢ Muscular symptoms such as weakness, cramps,
ā€¢ twitching, poor coordination and paralysis develop
ā€¢ 7. Severe conditions of water intoxication result in:
ā€¢ i. Delirium (extreme mental condition characterized
ā€¢ by confused state and illusion)
ā€¢ ii. Seizures (sudden uncontrolled involuntary muscular
ā€¢ contractions)
ā€¢ iii. Coma (profound state of unconsciousness, in
ā€¢ which the person fails to respond to external
ā€¢ stimuli and cannot perform voluntary actions).
ā€¢ Treatment
ā€¢ Mild water intoxication requires only fluid restriction.
In
ā€¢ very severe cases, the treatment includes:
ā€¢ 1. Diuretics to increase water loss through urine
ā€¢ 2. Antidiuretic hormone (ADH) receptor antagonists
ā€¢ to prevent ADH-induced reabsorption of water from
ā€¢ renal tubules
ā€¢ 3. Intravenous administration of saline to restore
ā€¢ sodium.
ā€¢ PROPERTIES OF RED BLOOD CELLS
ā€¢ ā€žROULEAUX FORMATION
ā€¢ When blood is taken out of the blood vessel,
the RBCs
ā€¢ pile up one above another like the pile of
coins. This property of the RBCs is called
rouleaux (pleural = rouleau) formation
ā€¢ SPECIFIC GRAVITY
ā€¢ Specific gravity of RBC is 1.092 to 1.101.
ā€¢ ā€žPACKED CELL VOLUME
ā€¢ Packed cell volume (PCV) is the proportion of
blood occupied by RBCs expressed in
percentage. It is also called hematocrit value.
It is 45% of the blood and the plasma volume
is 55%
ā€¢ SUSPENSION STABILITY
ā€¢ During circulation, the RBCs remain
suspended uniformly in the blood. This
property of the RBCs is called the suspension
stability
ā€¢ LIFESPAN OF RED BLOOD CELLS
ā€¢ Average lifespan of RBC is about 120 days.
After the lifetime the senile (old) RBCs are
destroyed in reticuloendothelial system
FATE OF RED BLOOD CELLS
ā€¢ When the cells become older (120 days), the
cell membrane becomes more fragile.
Diameter of the capillaries is less or equal to
that of RBC. Younger RBCs can pass through
the capillaries easily. However, because of the
fragile nature, the older cells are destroyed
while trying to squeeze through the
capillaries.
ā€¢ The destruction occurs mainly in the
capillaries of red pulp of spleen because the
diameter of splenic capillaries is very small.
ā€¢ So, the spleen is called ā€˜graveyard of RBCsā€™.
ā€¢ Destroyed RBCs are fragmented and
hemoglobin is released from the fragmented
parts. Hemoglobin is immediately
phagocytized by macrophages of the body,
ā€¢ particularly the macrophages present in liver
(Kupffer cells), spleen and bone marrow
ā€¢ Hemoglobin is degraded into iron, globin and
porphyrin. Iron combines with the protein
called apoferritin to form ferritin, which is
stored in the body and reused later. Globin
enters the protein depot for later use .
Porphyrin is degraded into bilirubin, which is
excreted by liver through bile
ā€¢ Daily 10% RBCs, which are senile, are
destroyed in normal young healthy adults. It
causes release of about 0.6 g/dL of
hemoglobin into the plasma. From this 0.9 to
1.5 mg/dL bilirubin is formed
ā€¢ Hemoglobin is degraded into iron, globin and
porphyrin. Iron combines with the protein
called apoferritin to form ferritin, which is
stored in the body and reused later. Globin
enters the protein depot for later use.
ā€¢ Porphyrin is degraded into bilirubin, which is
excreted by liver through bile (Chapter 40).
ā€¢ Daily 10% RBCs, which are senile, are
destroyed in normal young healthy adults. It
causes release of about 0.6 g/dL of
hemoglobin into the plasma. From this 0.9 to
1.5 mg/dL bilirubin is formed.
ā€¢ FUNCTIONS OF RED BLOOD CELLS
ā€¢ Major function of RBCs is the transport of
respiratory gases. Following are the functions of
RBCs:
ā€¢ 1. Transport of Oxygen from the Lungs to the
Tissues
ā€¢ Hemoglobin in RBC combines with oxygen to
form oxyhemoglobin. About 97% of oxygen is
transported in blood in the form of
oxyhemoglobin
ā€¢ Transport of Carbon Dioxide from the Tissues
to the Lungs
ā€¢ Hemoglobin combines with carbon dioxide
and form carbhemoglobin. About 30% of
carbon dioxide is transported in this form.
ā€¢ RBCs contain a large amount of the
carbonicanhydrase. This enzyme is necessary
for the formation of bicarbonate from water
and carbon dioxide.
ā€¢ Thus, it helps to transport carbon dioxide in
them form of bicarbonate from tissues to
lungs. About 63% of carbon dioxide is
transported in this form.
3. Buffering Action in Blood
Hemoglobin functions as a good buffer. By this
action,
it regulates the hydrogen ion concentration and
thereby
plays a role in the maintenance of acidbase
balance
ā€¢ 4. In Blood Group Determination
ā€¢ RBCs carry the blood group antigens like A
antigen,
ā€¢ B antigen and Rh factor. This helps in
determination of
ā€¢ blood group and enables to prevent reactions
due to
ā€¢ incompatible blood transfusion
VARIATIONS IN NUMBER OF RED
BLOOD CELLS
ā€¢ PHYSIOLOGICAL VARIATIONS
ā€¢ A. Increase in RBC Count
ā€¢ Increase in the RBC count is known as
polycythemia. It occurs in both physiological and
pathological conditions.
ā€¢ When it occurs in physiological conditions it is
called physiological polycythemia. The increase in
number during this condition is marginal and
temporary. It occurs in the following conditions
ā€¢ Age
ā€¢ At birth, the RBC count is 8 to 10 million/cu
mm of blood. The count decreases within 10
days after birth due to destruction of RBCs
causing physiological jaundice in
ā€¢ some newborn babies. However, in infants
and growing children, the cell count is more
than the value in adults
ā€¢ Sex-
ā€¢ Before puberty and after menopause in
females the RBC count is similar to that in
males. During reproductive period of females,
the count is less than that of males (4.5
million/cu mm).
ā€¢ High altitude
ā€¢ Inhabitants of mountains (above 10,000 feet
from mean sea level) have an increased RBC
count of more than 7 million/cu mm. It is due
to hypoxia (decreased oxygen supply to
tissues) in high altitude. Hypoxia stimulates
kidney to secrete a hormone called
erythropoietin.
ā€¢ 4. Muscular exercise
ā€¢ There is a temporary increase in RBC count
after exercise. It is because of mild hypoxia
and contraction of spleen. Spleen stores RBCs
ā€¢ increases the sympathetic activity resulting in
secretion of adrenaline from adrenal medulla
ā€¢ Emotional conditions
ā€¢ RBC count increases during the emotional
conditions such as anxiety. It is because of
increase in the sym pa thetic activity as in the
case of muscular exercise
ā€¢ Increased environmental temperature
ā€¢ Increase in atmospheric temperature
increases RBC count. Generally increased
temperature increases all the activities in the
body including production of RBCs.
ā€¢ 7. After meals
ā€¢ There is a slight increase in the RBC count
after taking meals. It is because of need for
more oxygen for metabolic activities.
ā€¢ B. Decrease in RBC Count
ā€¢ Decrease in RBC count occurs in the following
physiological conditions:
ā€¢ 1. High barometric pressures
ā€¢ At high barometric pressures as in deep sea,
when the oxygen tension of blood is higher,
the RBC count decreases.
ā€¢ 2. During sleep
ā€¢ RBC count decreases slightly during sleep and
immediately
ā€¢ after getting up from sleep. Generally all the
ā€¢ activities of the body are decreased during
sleep including
ā€¢ production of RBCs
ā€¢ Pregnancy
ā€¢ In pregnancy, the RBC count decreases. It is
because
ā€¢ of increase in ECF volume. Increase in ECF
volume,
ā€¢ increases the plasma volume also resulting in
hemodilution.
ā€¢ So, there is a relative reduction in the RBC
count
Erythropoiesis
ā€¢ DEFINITION
ā€¢ Erythropoiesis is the process of the origin,
development
ā€¢ and maturation of erythrocytes. Hemopoiesis
or hematopoiesis
ā€¢ is the process of origin, development and
ā€¢ maturation of all the blood cells.
ā€¢ SITE OF ERYTHROPOIESIS
ā€¢ ā€žIN FETAL LIFE
ā€¢ In fetal life, the erythropoiesis occurs in three
stages:
ā€¢ 1. Mesoblastic Stage
ā€¢ During the first two months of intrauterine
life, the RBCs
ā€¢ are produced from mesenchyme of yolk sac
ā€¢ Hepatic Stage
ā€¢ From third month of intrauterine life, liver is
the main
ā€¢ organ that produces RBCs. Spleen and
lymphoid
ā€¢ organs are also involved in erythropoiesis.
ā€¢ Myeloid Stage
ā€¢ During the last three months of intrauterine
life, the RBCs
ā€¢ are produced from red bone marrow and
liver.
ā€¢ IN NEWBORN BABIES, CHILDREN AND ADULTS
ā€¢ In newborn babies, growing children and adults,
RBCs
ā€¢ are produced only from the red bone marrow.
ā€¢ 1. Up to the age of 20 years: RBCs are produced
from
ā€¢ red bone marrow of all bones (long bones and all
ā€¢ the flat bones).
ā€¢ After the age of 20 years: RBCs are produced
ā€¢ from membranous bones like vertebra, sternum,
ā€¢ ribs, scapula, iliac bones and skull bones and from
ā€¢ the ends of long bones. After 20 years of age,
ā€¢ the shaft of the long bones becomes yellow bone
ā€¢ marrow because of fat deposition and looses the
ā€¢ erythropoietic function
ā€¢ In adults, liver and spleen may produce the blood
cells if the bone marrow is destroyed or fibrosed.
Collectively bone marrow is almost equal to liver
in size and weight.
ā€¢ It is also as active as liver. Though bone marrow is
the site of production of all blood cells,
comparatively 75% of the bone marrow is
involved in the production of leukocytes and only
25% is involved in the production of erythrocytes
ā€¢ But still, the leukocytes are less in number
than the erythrocytes, the ratio being 1:500.
This is mainly because of the lifespan of these
cells. Lifespan of erythrocytes is 120 days
whereas the lifespan of leukocytes is very
short ranging from one to ten days. So the
leukocytes
ā€¢ need larger production than erythrocytes to
maintain the required number
PROCESS OF ERYTHROPOIESIS
ā€¢ ā€žSTEM CELLS
ā€¢ Stem cells are the primary cells capable of
self-renewal and differentiating into
specialized cells
ā€¢ Hemopoietic stem cells are the primitive cells
in the bone marrow, which give rise to the
blood cells.
ā€¢ Hemopoietic stem cells in the bone marrow
are called uncommitted pluripotent
hemopoietic stem cells (PHSC).
ā€¢ PHSC is defined as a cell that can give rise to
all types of blood cells. In early stages, the
PHSC are not designed to form a particular
type of blood cell.
ā€¢ And it is also not possible to determine the
blood cell to be developed from these cells
ā€¢ In adults, only a few number of these cells are
present. But the best source of these cells is
the umbilical cord blood.
ā€¢ When the cells are designed to form a
particular type of blood cell, the uncommitted
PHSCs are called committed PHSCs.
Committed PHSC is defined as a cell, which is
restricted to give rise to one group of blood
cells
ā€¢ Committed PHSCs are of two types:
ā€¢ 1. Lymphoid stem cells (LSC) which give rise to
ā€¢ lymphocytes and natural killer (NK) cells
ā€¢ 2. Colony forming blastocytes, which give rise to
ā€¢ myeloid cells. Myeloid cells are the blood cells
other
ā€¢ than lymphocytes. When grown in cultures, these
ā€¢ cells form colonies hence the name colony
forming blastocytes.
ā€¢ Different units of colony forming cells are:
ā€¢ i. Colony forming unit-erythrocytes (CFU-E) ā€“
ā€¢ Cells of this unit develop into erythrocytes
ā€¢ ii. Colony forming unit-granulocytes/monocytes
ā€¢ (CFU-GM) ā€“ These cells give rise to granulocytes
ā€¢ (neutrophils, basophils and eosinophils) and
monocytes
ā€¢ iii. Colony forming unit-megakaryocytes (CFU-M)
ā€¢ ā€“ Platelets are developed from these cells.
CHANGES DURING ERYTHROPOIESIS
Cells of CFU-E pass through different stages and finally
become the matured RBCs. During these stages four
important changes are noticed.
1. Reduction in size of the cell (from the diameter of
25
to 7.2 Ī¼)
2. Disappearance of nucleoli and nucleus
STAGES OF ERYTHROPOIESIS
ā€¢ ā€ž
ā€¢ Various stages between CFU-E cells and matured
RBCs
ā€¢ 1. Proerythroblast
ā€¢ 2. Early normoblast
ā€¢ 3. Intermediate normoblast
ā€¢ 4. Late normoblast
ā€¢ 5. Reticulocyte
ā€¢ 6. Matured erythrocyte
ā€¢ 1. Proerythroblast (Megaloblast)
ā€¢ Proerythroblast or megaloblast is the first cell
derived from CFU-E. It is very large in size with
a diameter of about 20 Ī¼. Its nucleus is large
and occupies the cell almost completely. The
nucleus has two or more nucleoli and a
reticular network.
Proerythroblast does not contain
hemoglobin. The cytoplasm is basophilic in nature.
Proerythroblast multiplies several times and finally
forms
the cell of next stage called early normoblast. Synthesis
of hemoglobin starts in this stage. However,
appearance
of hemoglobin occurs only in intermediate normoblast
ā€¢ Early Normoblast
ā€¢ The early normoblast is little smaller than
proerythroblast with a diameter of about 15
Ī¼. In the nucleus, the nucleoli disappear.
Condensation of chromatin network occurs.
The condensed network becomes dense. The
cytoplasm is basophilic in nature. So, this cell
is also called basophilic erythroblast. This cell
develops into next stage called intermediate
normoblast
ā€¢ Intermediate Normoblast
ā€¢ Cell is smaller than the early normoblast with a
diameter of 10 to 12 Ī¼. The nucleus is still
present. But, the chromatin network shows
further condensation. The hemoglobin starts
appearing.
ā€¢ Cytoplasm is already basophilic. Now, because of
the presence of hemoglobin, it stains with both
acidic as well as basic stains. So this cell is called
polychromophilic or polychromatic erythroblast.
This cell develops into next stage called late
normoblast
ā€¢ 4. Late Normoblast
ā€¢ Diameter of the cell decreases further to
about 8 to 10 Ī¼.
ā€¢ Nucleus becomes very small with very much
condensed chromatin network and it is known
as ink-spot nucleus
ā€¢ Quantity of hemoglobin increases. And the cytoplasm
ā€¢ called orthochromic erythroblast. In the final stage of
ā€¢ late normoblast just before it passes to next stage, the
ā€¢ nucleus disintegrates and disappears. The process by
ā€¢ which nucleus disappears is called pyknosis. The final
ā€¢ remnant is extruded from the cell. Late normoblast
ā€¢ develops into the next stage called reticulocyte
ā€¢ Reticulocyte
ā€¢ Reticulocyte is otherwise known as immature RBC.
ā€¢ It is slightly larger than matured RBC. The cytoplasm
ā€¢ contains the reticular network or reticulum, which is
ā€¢ formed by remnants of disintegrated organelles. Due to
ā€¢ the reticular network, the cell is called reticulocyte. The
ā€¢ reticulum of reticulocyte stains with supravital stain
ā€¢ In newborn babies, the reticulocyte count is 2% to
ā€¢ 6% of RBCs, i.e. 2 to 6 reticulocytes are present for
ā€¢ every 100 RBCs. The number of reticulocytes
decreasesduring the first week after birth. Later, the
reticulocyte
ā€¢ count remains constant at or below 1% of RBCs. The
ā€¢ number increases whenever production and release of
ā€¢ RBCs increase
ā€¢ Reticulocyte is basophilic due to the presence
of
ā€¢ remnants of disintegrated Golgi apparatus,
mitochondria
ā€¢ and other organelles of cytoplasm. During this
stage, the
ā€¢ cells enter the blood capillaries through
capillary membrane
ā€¢ from site of production by diapedesis.
ā€¢ Reticular network disappears and the cell becomes the
ā€¢ matured RBC and attains the biconcave shape. The cell
ā€¢ decreases in size to 7.2 Ī¼ diameter. The matured RBC
ā€¢ is with hemoglobin but without nucleus.
ā€¢ It requires 7 days for the development and maturation
ā€¢ of RBC from proerythroblast. It requires 5 days up to
the
ā€¢ stage of reticulocyte. Reticulocyte takes 2 more days to
ā€¢ become the matured RBC.
ā€¢ FACTORS NECESSARY FOR
ā€¢ ERYTHROPOIESIS
ā€¢ Development and maturation of erythrocytes
require varie -
ā€¢ ty of factors, which are classified into three
categories:
ā€¢ 1. General factors
ā€¢ 2. Maturation factors
ā€¢ 3. Factors necessary for hemoglobin formation
ā€¢ GENERAL FACTORS
ā€¢ General factors necessary for erythropoiesis
are:
ā€¢ i. Erythropoietin
ā€¢ ii. Thyroxine
ā€¢ iii. Hemopoietic growth factors
ā€¢ iv. Vitamins.
ā€¢ i. Erythropoietin
ā€¢ Most important general factor for
erythropoiesis is
ā€¢ the hormone called erythropoietin. It is also
called
ā€¢ hemopoietin or erythrocyte stimulating factor
ā€¢ i. Erythropoietin
ā€¢ Most important general factor for
erythropoiesis is
ā€¢ the hormone called erythropoietin. It is also
called
ā€¢ hemopoietin or erythrocyte stimulating factor
ā€¢ Vitamins
ā€¢ Some vitamins are also necessary for the process
of
ā€¢ erythropoiesis. Deficiency of these vitamins cause
ā€¢ anemia associated with other disorders.
ā€¢ Vitamins necessary for erythropoiesis:
ā€¢ a. Vitamin B: Its deficiency causes anemia and
ā€¢ pellagra (disease characterized by skin lesions,
ā€¢ diarrhea, weakness, nervousness and dementia).
ā€¢ b. Vitamin C: Its deficiency causes anemia
ā€¢ and scurvy (ancient disease characterized
ā€¢ by impaired collagen synthesis resulting in
ā€¢ rough skin, bleeding gum, loosening of teeth,
ā€¢ poor wound healing, bone pain, lethargy and
ā€¢ emotional changes).
ā€¢ c. Vitamin D: Its deficiency causes anemia and
ā€¢ rickets (bone disease ā€“ Chapter 68).
ā€¢ d. Vitamin E: Its deficiency leads to anemia and
ā€¢ malnutrition
ā€¢ MATURATION FACTORS
ā€¢ Vitamin B12, intrinsic factor and folic acid are necessary for
the maturation of RBCs.
ā€¢ 1. Vitamin B12 (Cyanocobalamin)
ā€¢ Vitamin B12 is the maturation factor necessary for
erythropoiesis.
ā€¢ Source:
ā€¢ Vitamin B12 is called extrinsic factor since it is obtained
mostly from diet. Its absorption from intestine requires the
presence of intrinsic factor of Castle. Vitamin B12 is stored
mostly in liver and in small quantity in muscle.
ā€¢ When necessary, it is transported to the bone marrow to
promote maturation of RBCs. It is also produced in the
large intestine by the intestinal flora.
ā€¢ Intrinsic Factor of Castle
ā€¢ Intrinsic factor of castle is produced in gastric
mucosa by the parietal cells of the gastric glands.
It is essential for the absorption of vitamin B12
from intestine.
ā€¢ In the absence of intrinsic factor, vitamin B12 is
not absorbed from intestine. This leads to
pernicious anaemia.
ā€¢ Deficiency of intrinsic factor occurs in:
ā€¢ i. Severe gastritis
ā€¢ ii. Ulcer
ā€¢ iii. Gastrectomy.
ā€¢ Folic Acid
ā€¢ Folic acid is also essential for maturation. It is
required for the synthesis of DNA. In the
absence of folic acid, the synthesis of DNA
decreases causing failure of maturation. This
leads to anemia in which the cells are larger
and appear in megaloblastic
(proerythroblastic) stage.
ā€¢ Hemoglobin (Hb) is the iron containing
coloring matter of red blood cell (RBC). It is a
chromoprotein forming 95% of dry weight of
RBC and 30% to 34% of wet weight.
ā€¢ Function of hemoglobin is to carry the
respiratory gases oxygen and carbon dioxide.
It also acts as a buffer.
ā€¢ Molecular weight of hemoglobin is 68,000.
ā€¢ Average hemoglobin (Hb) content in blood is 14
to 16 g/dL.
ā€¢ However, the value varies depending upon the
age and sex of the individual.
ā€¢ Age
ā€¢ At birth : 25 g/dL
ā€¢ After 3rd month : 20 g/dL
ā€¢ After 1 year : 17 g/dL
ā€¢ From puberty onwards : 14 to 16 g/dL
ā€¢ At the time of birth, hemoglobin content is very
high because of increased number of RBCs.
ā€¢ Sex
ā€¢ In adult males : 15 g/dL
ā€¢ In adult females : 14.5 g/dL
ā€¢ FUNCTIONS OF HEMOGLOBIN
ā€¢ ā€žTRANSPORT OF RESPIRATORY GASES
ā€¢ Main function of hemoglobin is the transport of
respiratory gases:
ā€¢ 1. Oxygen from the lungs to tissues.
ā€¢ 2. Carbon dioxide from tissues to lungs.
ā€¢ 1. Transport of Oxygen
ā€¢ When oxygen binds with hemoglobin, a physical
process called oxygenation occurs, resulting in the
formation of oxyhemoglobin. The iron remains in
ferrous state in this compound.
ā€¢ Oxyhemoglobin is an unstable compound and the
combination is reversible, i.e. when more oxygen is
available, it combines with hemoglobin and whenever
oxygen is required, hemoglobin can release oxygen
readily
ā€¢ Transport of Carbon Dioxide
ā€¢ When carbon dioxide binds with hemoglobin,
carbhemoglobin is formed. It is also an
unstable compound and the combination is
reversible, i.e. the carbon dioxide can be
released from this compound. The affinity
ofhemoglobin for carbon dioxide is 20 times
more than that for oxygen
ā€¢ BUFFER ACTION
ā€¢ Hemoglobin acts as a buffer and plays an
important role in acidbase balance
ā€¢ STRUCTURE OF HEMOGLOBIN
ā€¢ Hemoglobin is a conjugated protein. It consists
of a protein combined with an iron containing
pigment. The protein part is globin and the
ironcontaining pigment
is heme. Heme also forms a part of the
structure of myoglobin (oxygenbindin
pigment in muscles) and neuroglobin
(oxygenbinding pigment in brain).
ā€¢ IRON
ā€¢ Normally, it is present in ferrous (Fe2+) form.
It is in unstable or loose form. In some
abnormal conditions, the iron is converted
into ferric (Fe3+) state, which is a stable form.
PORPHYRIN
ā€¢ The pigment part of heme is called porphyrin.
It is formed by four pyrrole rings (tetrapyrrole)
called, I, II, III and IV. The pyrrole rings are
attached to one another by methane (CH4)
bridges.
ā€¢ The iron is attached to ā€˜Nā€™ of each pyrrole ring
and ā€˜Nā€™ of globin molecule.
ā€¢ GLOBIN
ā€¢ Globin contains four polypeptide chains.
Among the four polypeptide chains, two are
chains and two are Ī±-chains.
ā€¢ TYPES OF NORMAL HEMOGLOBIN
ā€¢ Hemoglobin is of two types:
ā€¢ 1. Adult hemoglobin ā€“ HbA
ā€¢ 2. Fetal hemoglobin ā€“ HbF
ā€¢ Replacement of fetal hemoglobin by adult
hemoglobin starts immediately after birth.
ā€¢ It is completed at about 10th to 12th week
after birth. Both the types of hemoglobin
differ from each other structurally and
functionally.
ā€¢ Structural Difference
ā€¢ In adult hemoglobin, the globin contains two
Ī±-chains and two Ī²-chains. In fetal
hemoglobin, there are two Ī± chains and two
Ī³-chains instead of Ī²-chains.
ā€¢ Functional Difference
ā€¢ Functionally, fetal hemoglobin has more
affinity for oxygen than that of adult
hemoglobin. And, the oxygen hemoglobin
dissociation curve of fetal blood is shifted to
left.
ā€¢ ABNORMAL HEMOGLOBIN
ā€¢ Abnormal types of hemoglobin or hemoglobin
variants are the pathologic mutant forms of
hemoglobin. These variants are produced
because of structural changes in the polypeptide
chains caused by mutation in the genes of the
globin chains. Most of the mutations do not
produce any serious problem. Occasionally, few
mutations result in some disorders.
ā€¢ There are two categories of abnormal
hemoglobin:
ā€¢ 1. Hemoglobinopathies
ā€¢ 2. Hemoglobin in thalassemia and related
disorders

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  • 1. BLOOD ā€¢ Your body has over 160,000 km (100,000 miles) of blood vessels. which if laid end to end, would stretch 2 and a half times around the Earth. ā€¢ There are four main blood cell types, A, B, AB, and O. Each can be positive or Negative. AB is the Universal recipient while O negative is the universal donor.
  • 2. ā€¢ In an average life time the human heart pumps 1.5 million barrels of blood (that's enough to fill 200 train tank cars).
  • 3. One unit of blood can be separated into several components: red blood cells, plasma, platelets and cryoprecipitate. Pregnant women have roughly 50% more blood by week 20 of pregnancy than they did before conception
  • 4. ā€¢ In emergencies, coconut water can be used as a substitute for blood plasma. ā€¢ A blood cell can make a complete circuit of your body in less than 30 seconds.
  • 5. There are about .2 mg of gold in your blood stream Your blood accounts for 8% of your body weight
  • 6. ā€¢ Mosquitoes prefer people with blood type "Oā€œ ā€¢ Every year, the average meat eating American ingests enough blood to fill a can of soda
  • 7. ā€¢ Those strange bright white dots you see floating around when you look at the sky are white blood cells (it's called blue field entoptic phenomenon) ā€¢ George Washington was bled to death by doctors. This is because bloodletting was a common practice back then. It was supposed to get rid of "bad blood"
  • 8. ā€¢ A newborn baby has about one cup of blood in his body ā€¢ 2. Not every animal has red blood. Spiders, lobsters and snails have blue blood due to the presence of the protein haemocyanin which contains copper.
  • 9. ā€¢ The amount of blood in a pregnant woman's body will have increased by 50% by the 20th week of pregnancy. ā€¢ Some Japanese people believe that blood type is an indicator of a personā€™s personality. There are even novelty goods themed after blood types.
  • 10. ā€¢ . Nothing is left to chance for the President of the United States. The Presidential car stores the President's blood type in the boot of the car just in case of emergencies. ā€¢ Research has shown that mosquitoes prefer blood type O. It would take 1,200,000 mosquitoes, each sucking once, to totally drain a human of blood.
  • 11. ā€¢ Larger animals have slower heart rates than smaller animals. This means that the blood in their body takes longer to circulate around. For example, a blue whaleā€™s heart only beats 5 times per minute while humans beat closer to 75 per minute.
  • 12. ā€¢ There has been an example of blood becoming a dark green colour. Surgeons operating on a 42-year-old Canadian man got a shock when they discovered dark green blood coursing through his arteries, like Star Trekā€˜s Mr Spock. It's thought this was caused by of a type of migraine medication. ā€¢
  • 13. ā€¢ Ancient Egyptians believed that wine was the blood of people who dared to battle against Gods. The reason why they believed this is that drinking wine temporarily made people crazy and drove them out of their senses. This is precisely why ancient Egyptians avoided drinking wine.
  • 14. BODY FLUIDS ā€¢ WATER INTOXICATION OR OVERHYDRATION ā€¢ Definition ā€¢ Water intoxication is the condition characterized by great increase in the water content of the body. It is also called overhydration, hyperhydration, water excess or water poisoning.
  • 15. ā€¢ But there are some conditions that can produce water intoxication. ā€¢ 1. Heart failure in which heart cannot pump blood properly ā€¢ 2. Renal disorders in which kidney fails to excrete enough water in urine ā€¢ 3. Hypersecretion of antidiuretic hormone as in the case of syndrome of inappropriate hypersecretion of antidiuretic hormone (SIADH) ā€¢ 4. Intravenous administration of unduly large amount of medications and fluids than the personā€™s body can excrete
  • 16. ā€¢ Infants have greater risk of developing water intoxication in the first month of life, when the filtration mechanism of the kidney is underdeveloped and cannot excrete the fluid rapidly ā€¢ 6. Water intoxication is also common in children having swimming practice, since they are more prone to drink too much of water while swimming ā€¢ 7. An adult (whose heart and kidneys are functioning normally) can develop water intoxication, if the person consumes about 8 L of water everyday regularly.
  • 17. ā€¢ Signs and Symptoms ā€¢ 1. Since the brain is more vulnerable to the effects of ā€¢ water intoxication, behavioral changes appear first ā€¢ 2. Person becomes drowsy and inattentive ā€¢ 3. Nausea and vomiting occur ā€¢ 4. There is sudden loss of weight, followed by weakness ā€¢ and blurred vision ā€¢ 5. Anemia, acidosis, cyanosis, hemorrhage and shock ā€¢ are also common
  • 18. ā€¢ Muscular symptoms such as weakness, cramps, ā€¢ twitching, poor coordination and paralysis develop ā€¢ 7. Severe conditions of water intoxication result in: ā€¢ i. Delirium (extreme mental condition characterized ā€¢ by confused state and illusion) ā€¢ ii. Seizures (sudden uncontrolled involuntary muscular ā€¢ contractions) ā€¢ iii. Coma (profound state of unconsciousness, in ā€¢ which the person fails to respond to external ā€¢ stimuli and cannot perform voluntary actions).
  • 19. ā€¢ Treatment ā€¢ Mild water intoxication requires only fluid restriction. In ā€¢ very severe cases, the treatment includes: ā€¢ 1. Diuretics to increase water loss through urine ā€¢ 2. Antidiuretic hormone (ADH) receptor antagonists ā€¢ to prevent ADH-induced reabsorption of water from ā€¢ renal tubules ā€¢ 3. Intravenous administration of saline to restore ā€¢ sodium.
  • 20.
  • 21. ā€¢ PROPERTIES OF RED BLOOD CELLS ā€¢ ā€žROULEAUX FORMATION ā€¢ When blood is taken out of the blood vessel, the RBCs ā€¢ pile up one above another like the pile of coins. This property of the RBCs is called rouleaux (pleural = rouleau) formation
  • 22. ā€¢ SPECIFIC GRAVITY ā€¢ Specific gravity of RBC is 1.092 to 1.101. ā€¢ ā€žPACKED CELL VOLUME ā€¢ Packed cell volume (PCV) is the proportion of blood occupied by RBCs expressed in percentage. It is also called hematocrit value. It is 45% of the blood and the plasma volume is 55%
  • 23. ā€¢ SUSPENSION STABILITY ā€¢ During circulation, the RBCs remain suspended uniformly in the blood. This property of the RBCs is called the suspension stability
  • 24. ā€¢ LIFESPAN OF RED BLOOD CELLS ā€¢ Average lifespan of RBC is about 120 days. After the lifetime the senile (old) RBCs are destroyed in reticuloendothelial system
  • 25. FATE OF RED BLOOD CELLS ā€¢ When the cells become older (120 days), the cell membrane becomes more fragile. Diameter of the capillaries is less or equal to that of RBC. Younger RBCs can pass through the capillaries easily. However, because of the fragile nature, the older cells are destroyed while trying to squeeze through the capillaries.
  • 26. ā€¢ The destruction occurs mainly in the capillaries of red pulp of spleen because the diameter of splenic capillaries is very small. ā€¢ So, the spleen is called ā€˜graveyard of RBCsā€™.
  • 27. ā€¢ Destroyed RBCs are fragmented and hemoglobin is released from the fragmented parts. Hemoglobin is immediately phagocytized by macrophages of the body, ā€¢ particularly the macrophages present in liver (Kupffer cells), spleen and bone marrow
  • 28. ā€¢ Hemoglobin is degraded into iron, globin and porphyrin. Iron combines with the protein called apoferritin to form ferritin, which is stored in the body and reused later. Globin enters the protein depot for later use . Porphyrin is degraded into bilirubin, which is excreted by liver through bile
  • 29. ā€¢ Daily 10% RBCs, which are senile, are destroyed in normal young healthy adults. It causes release of about 0.6 g/dL of hemoglobin into the plasma. From this 0.9 to 1.5 mg/dL bilirubin is formed
  • 30. ā€¢ Hemoglobin is degraded into iron, globin and porphyrin. Iron combines with the protein called apoferritin to form ferritin, which is stored in the body and reused later. Globin enters the protein depot for later use. ā€¢ Porphyrin is degraded into bilirubin, which is excreted by liver through bile (Chapter 40). ā€¢ Daily 10% RBCs, which are senile, are destroyed in normal young healthy adults. It causes release of about 0.6 g/dL of hemoglobin into the plasma. From this 0.9 to 1.5 mg/dL bilirubin is formed.
  • 31. ā€¢ FUNCTIONS OF RED BLOOD CELLS ā€¢ Major function of RBCs is the transport of respiratory gases. Following are the functions of RBCs: ā€¢ 1. Transport of Oxygen from the Lungs to the Tissues ā€¢ Hemoglobin in RBC combines with oxygen to form oxyhemoglobin. About 97% of oxygen is transported in blood in the form of oxyhemoglobin
  • 32. ā€¢ Transport of Carbon Dioxide from the Tissues to the Lungs ā€¢ Hemoglobin combines with carbon dioxide and form carbhemoglobin. About 30% of carbon dioxide is transported in this form.
  • 33.
  • 34. ā€¢ RBCs contain a large amount of the carbonicanhydrase. This enzyme is necessary for the formation of bicarbonate from water and carbon dioxide. ā€¢ Thus, it helps to transport carbon dioxide in them form of bicarbonate from tissues to lungs. About 63% of carbon dioxide is transported in this form.
  • 35. 3. Buffering Action in Blood Hemoglobin functions as a good buffer. By this action, it regulates the hydrogen ion concentration and thereby plays a role in the maintenance of acidbase balance
  • 36. ā€¢ 4. In Blood Group Determination ā€¢ RBCs carry the blood group antigens like A antigen, ā€¢ B antigen and Rh factor. This helps in determination of ā€¢ blood group and enables to prevent reactions due to ā€¢ incompatible blood transfusion
  • 37. VARIATIONS IN NUMBER OF RED BLOOD CELLS ā€¢ PHYSIOLOGICAL VARIATIONS ā€¢ A. Increase in RBC Count ā€¢ Increase in the RBC count is known as polycythemia. It occurs in both physiological and pathological conditions. ā€¢ When it occurs in physiological conditions it is called physiological polycythemia. The increase in number during this condition is marginal and temporary. It occurs in the following conditions
  • 38. ā€¢ Age ā€¢ At birth, the RBC count is 8 to 10 million/cu mm of blood. The count decreases within 10 days after birth due to destruction of RBCs causing physiological jaundice in ā€¢ some newborn babies. However, in infants and growing children, the cell count is more than the value in adults
  • 39. ā€¢ Sex- ā€¢ Before puberty and after menopause in females the RBC count is similar to that in males. During reproductive period of females, the count is less than that of males (4.5 million/cu mm).
  • 40. ā€¢ High altitude ā€¢ Inhabitants of mountains (above 10,000 feet from mean sea level) have an increased RBC count of more than 7 million/cu mm. It is due to hypoxia (decreased oxygen supply to tissues) in high altitude. Hypoxia stimulates kidney to secrete a hormone called erythropoietin.
  • 41. ā€¢ 4. Muscular exercise ā€¢ There is a temporary increase in RBC count after exercise. It is because of mild hypoxia and contraction of spleen. Spleen stores RBCs ā€¢ increases the sympathetic activity resulting in secretion of adrenaline from adrenal medulla
  • 42. ā€¢ Emotional conditions ā€¢ RBC count increases during the emotional conditions such as anxiety. It is because of increase in the sym pa thetic activity as in the case of muscular exercise
  • 43. ā€¢ Increased environmental temperature ā€¢ Increase in atmospheric temperature increases RBC count. Generally increased temperature increases all the activities in the body including production of RBCs. ā€¢ 7. After meals ā€¢ There is a slight increase in the RBC count after taking meals. It is because of need for more oxygen for metabolic activities.
  • 44.
  • 45. ā€¢ B. Decrease in RBC Count ā€¢ Decrease in RBC count occurs in the following physiological conditions: ā€¢ 1. High barometric pressures ā€¢ At high barometric pressures as in deep sea, when the oxygen tension of blood is higher, the RBC count decreases.
  • 46. ā€¢ 2. During sleep ā€¢ RBC count decreases slightly during sleep and immediately ā€¢ after getting up from sleep. Generally all the ā€¢ activities of the body are decreased during sleep including ā€¢ production of RBCs
  • 47. ā€¢ Pregnancy ā€¢ In pregnancy, the RBC count decreases. It is because ā€¢ of increase in ECF volume. Increase in ECF volume, ā€¢ increases the plasma volume also resulting in hemodilution. ā€¢ So, there is a relative reduction in the RBC count
  • 48. Erythropoiesis ā€¢ DEFINITION ā€¢ Erythropoiesis is the process of the origin, development ā€¢ and maturation of erythrocytes. Hemopoiesis or hematopoiesis ā€¢ is the process of origin, development and ā€¢ maturation of all the blood cells.
  • 49. ā€¢ SITE OF ERYTHROPOIESIS ā€¢ ā€žIN FETAL LIFE ā€¢ In fetal life, the erythropoiesis occurs in three stages: ā€¢ 1. Mesoblastic Stage ā€¢ During the first two months of intrauterine life, the RBCs ā€¢ are produced from mesenchyme of yolk sac
  • 50. ā€¢ Hepatic Stage ā€¢ From third month of intrauterine life, liver is the main ā€¢ organ that produces RBCs. Spleen and lymphoid ā€¢ organs are also involved in erythropoiesis.
  • 51. ā€¢ Myeloid Stage ā€¢ During the last three months of intrauterine life, the RBCs ā€¢ are produced from red bone marrow and liver.
  • 52. ā€¢ IN NEWBORN BABIES, CHILDREN AND ADULTS ā€¢ In newborn babies, growing children and adults, RBCs ā€¢ are produced only from the red bone marrow. ā€¢ 1. Up to the age of 20 years: RBCs are produced from ā€¢ red bone marrow of all bones (long bones and all ā€¢ the flat bones).
  • 53. ā€¢ After the age of 20 years: RBCs are produced ā€¢ from membranous bones like vertebra, sternum, ā€¢ ribs, scapula, iliac bones and skull bones and from ā€¢ the ends of long bones. After 20 years of age, ā€¢ the shaft of the long bones becomes yellow bone ā€¢ marrow because of fat deposition and looses the ā€¢ erythropoietic function
  • 54. ā€¢ In adults, liver and spleen may produce the blood cells if the bone marrow is destroyed or fibrosed. Collectively bone marrow is almost equal to liver in size and weight. ā€¢ It is also as active as liver. Though bone marrow is the site of production of all blood cells, comparatively 75% of the bone marrow is involved in the production of leukocytes and only 25% is involved in the production of erythrocytes
  • 55. ā€¢ But still, the leukocytes are less in number than the erythrocytes, the ratio being 1:500. This is mainly because of the lifespan of these cells. Lifespan of erythrocytes is 120 days whereas the lifespan of leukocytes is very short ranging from one to ten days. So the leukocytes ā€¢ need larger production than erythrocytes to maintain the required number
  • 56. PROCESS OF ERYTHROPOIESIS ā€¢ ā€žSTEM CELLS ā€¢ Stem cells are the primary cells capable of self-renewal and differentiating into specialized cells ā€¢ Hemopoietic stem cells are the primitive cells in the bone marrow, which give rise to the blood cells.
  • 57. ā€¢ Hemopoietic stem cells in the bone marrow are called uncommitted pluripotent hemopoietic stem cells (PHSC). ā€¢ PHSC is defined as a cell that can give rise to all types of blood cells. In early stages, the PHSC are not designed to form a particular type of blood cell. ā€¢ And it is also not possible to determine the blood cell to be developed from these cells
  • 58. ā€¢ In adults, only a few number of these cells are present. But the best source of these cells is the umbilical cord blood. ā€¢ When the cells are designed to form a particular type of blood cell, the uncommitted PHSCs are called committed PHSCs. Committed PHSC is defined as a cell, which is restricted to give rise to one group of blood cells
  • 59.
  • 60. ā€¢ Committed PHSCs are of two types: ā€¢ 1. Lymphoid stem cells (LSC) which give rise to ā€¢ lymphocytes and natural killer (NK) cells ā€¢ 2. Colony forming blastocytes, which give rise to ā€¢ myeloid cells. Myeloid cells are the blood cells other ā€¢ than lymphocytes. When grown in cultures, these ā€¢ cells form colonies hence the name colony forming blastocytes.
  • 61. ā€¢ Different units of colony forming cells are: ā€¢ i. Colony forming unit-erythrocytes (CFU-E) ā€“ ā€¢ Cells of this unit develop into erythrocytes ā€¢ ii. Colony forming unit-granulocytes/monocytes ā€¢ (CFU-GM) ā€“ These cells give rise to granulocytes ā€¢ (neutrophils, basophils and eosinophils) and monocytes ā€¢ iii. Colony forming unit-megakaryocytes (CFU-M) ā€¢ ā€“ Platelets are developed from these cells.
  • 62. CHANGES DURING ERYTHROPOIESIS Cells of CFU-E pass through different stages and finally become the matured RBCs. During these stages four important changes are noticed. 1. Reduction in size of the cell (from the diameter of 25 to 7.2 Ī¼) 2. Disappearance of nucleoli and nucleus
  • 63. STAGES OF ERYTHROPOIESIS ā€¢ ā€ž ā€¢ Various stages between CFU-E cells and matured RBCs ā€¢ 1. Proerythroblast ā€¢ 2. Early normoblast ā€¢ 3. Intermediate normoblast ā€¢ 4. Late normoblast ā€¢ 5. Reticulocyte ā€¢ 6. Matured erythrocyte
  • 64. ā€¢ 1. Proerythroblast (Megaloblast) ā€¢ Proerythroblast or megaloblast is the first cell derived from CFU-E. It is very large in size with a diameter of about 20 Ī¼. Its nucleus is large and occupies the cell almost completely. The nucleus has two or more nucleoli and a reticular network.
  • 65. Proerythroblast does not contain hemoglobin. The cytoplasm is basophilic in nature. Proerythroblast multiplies several times and finally forms the cell of next stage called early normoblast. Synthesis of hemoglobin starts in this stage. However, appearance of hemoglobin occurs only in intermediate normoblast
  • 66. ā€¢ Early Normoblast ā€¢ The early normoblast is little smaller than proerythroblast with a diameter of about 15 Ī¼. In the nucleus, the nucleoli disappear. Condensation of chromatin network occurs. The condensed network becomes dense. The cytoplasm is basophilic in nature. So, this cell is also called basophilic erythroblast. This cell develops into next stage called intermediate normoblast
  • 67. ā€¢ Intermediate Normoblast ā€¢ Cell is smaller than the early normoblast with a diameter of 10 to 12 Ī¼. The nucleus is still present. But, the chromatin network shows further condensation. The hemoglobin starts appearing. ā€¢ Cytoplasm is already basophilic. Now, because of the presence of hemoglobin, it stains with both acidic as well as basic stains. So this cell is called polychromophilic or polychromatic erythroblast. This cell develops into next stage called late normoblast
  • 68. ā€¢ 4. Late Normoblast ā€¢ Diameter of the cell decreases further to about 8 to 10 Ī¼. ā€¢ Nucleus becomes very small with very much condensed chromatin network and it is known as ink-spot nucleus
  • 69. ā€¢ Quantity of hemoglobin increases. And the cytoplasm ā€¢ called orthochromic erythroblast. In the final stage of ā€¢ late normoblast just before it passes to next stage, the ā€¢ nucleus disintegrates and disappears. The process by ā€¢ which nucleus disappears is called pyknosis. The final ā€¢ remnant is extruded from the cell. Late normoblast ā€¢ develops into the next stage called reticulocyte
  • 70. ā€¢ Reticulocyte ā€¢ Reticulocyte is otherwise known as immature RBC. ā€¢ It is slightly larger than matured RBC. The cytoplasm ā€¢ contains the reticular network or reticulum, which is ā€¢ formed by remnants of disintegrated organelles. Due to ā€¢ the reticular network, the cell is called reticulocyte. The ā€¢ reticulum of reticulocyte stains with supravital stain
  • 71. ā€¢ In newborn babies, the reticulocyte count is 2% to ā€¢ 6% of RBCs, i.e. 2 to 6 reticulocytes are present for ā€¢ every 100 RBCs. The number of reticulocytes decreasesduring the first week after birth. Later, the reticulocyte ā€¢ count remains constant at or below 1% of RBCs. The ā€¢ number increases whenever production and release of ā€¢ RBCs increase
  • 72. ā€¢ Reticulocyte is basophilic due to the presence of ā€¢ remnants of disintegrated Golgi apparatus, mitochondria ā€¢ and other organelles of cytoplasm. During this stage, the ā€¢ cells enter the blood capillaries through capillary membrane ā€¢ from site of production by diapedesis.
  • 73. ā€¢ Reticular network disappears and the cell becomes the ā€¢ matured RBC and attains the biconcave shape. The cell ā€¢ decreases in size to 7.2 Ī¼ diameter. The matured RBC ā€¢ is with hemoglobin but without nucleus. ā€¢ It requires 7 days for the development and maturation ā€¢ of RBC from proerythroblast. It requires 5 days up to the ā€¢ stage of reticulocyte. Reticulocyte takes 2 more days to ā€¢ become the matured RBC.
  • 74. ā€¢ FACTORS NECESSARY FOR ā€¢ ERYTHROPOIESIS ā€¢ Development and maturation of erythrocytes require varie - ā€¢ ty of factors, which are classified into three categories: ā€¢ 1. General factors ā€¢ 2. Maturation factors ā€¢ 3. Factors necessary for hemoglobin formation
  • 75. ā€¢ GENERAL FACTORS ā€¢ General factors necessary for erythropoiesis are: ā€¢ i. Erythropoietin ā€¢ ii. Thyroxine ā€¢ iii. Hemopoietic growth factors ā€¢ iv. Vitamins.
  • 76. ā€¢ i. Erythropoietin ā€¢ Most important general factor for erythropoiesis is ā€¢ the hormone called erythropoietin. It is also called ā€¢ hemopoietin or erythrocyte stimulating factor
  • 77. ā€¢ i. Erythropoietin ā€¢ Most important general factor for erythropoiesis is ā€¢ the hormone called erythropoietin. It is also called ā€¢ hemopoietin or erythrocyte stimulating factor
  • 78. ā€¢ Vitamins ā€¢ Some vitamins are also necessary for the process of ā€¢ erythropoiesis. Deficiency of these vitamins cause ā€¢ anemia associated with other disorders. ā€¢ Vitamins necessary for erythropoiesis: ā€¢ a. Vitamin B: Its deficiency causes anemia and ā€¢ pellagra (disease characterized by skin lesions, ā€¢ diarrhea, weakness, nervousness and dementia).
  • 79. ā€¢ b. Vitamin C: Its deficiency causes anemia ā€¢ and scurvy (ancient disease characterized ā€¢ by impaired collagen synthesis resulting in ā€¢ rough skin, bleeding gum, loosening of teeth, ā€¢ poor wound healing, bone pain, lethargy and ā€¢ emotional changes). ā€¢ c. Vitamin D: Its deficiency causes anemia and ā€¢ rickets (bone disease ā€“ Chapter 68). ā€¢ d. Vitamin E: Its deficiency leads to anemia and ā€¢ malnutrition
  • 80. ā€¢ MATURATION FACTORS ā€¢ Vitamin B12, intrinsic factor and folic acid are necessary for the maturation of RBCs. ā€¢ 1. Vitamin B12 (Cyanocobalamin) ā€¢ Vitamin B12 is the maturation factor necessary for erythropoiesis. ā€¢ Source: ā€¢ Vitamin B12 is called extrinsic factor since it is obtained mostly from diet. Its absorption from intestine requires the presence of intrinsic factor of Castle. Vitamin B12 is stored mostly in liver and in small quantity in muscle. ā€¢ When necessary, it is transported to the bone marrow to promote maturation of RBCs. It is also produced in the large intestine by the intestinal flora.
  • 81. ā€¢ Intrinsic Factor of Castle ā€¢ Intrinsic factor of castle is produced in gastric mucosa by the parietal cells of the gastric glands. It is essential for the absorption of vitamin B12 from intestine. ā€¢ In the absence of intrinsic factor, vitamin B12 is not absorbed from intestine. This leads to pernicious anaemia. ā€¢ Deficiency of intrinsic factor occurs in: ā€¢ i. Severe gastritis ā€¢ ii. Ulcer ā€¢ iii. Gastrectomy.
  • 82. ā€¢ Folic Acid ā€¢ Folic acid is also essential for maturation. It is required for the synthesis of DNA. In the absence of folic acid, the synthesis of DNA decreases causing failure of maturation. This leads to anemia in which the cells are larger and appear in megaloblastic (proerythroblastic) stage.
  • 83. ā€¢ Hemoglobin (Hb) is the iron containing coloring matter of red blood cell (RBC). It is a chromoprotein forming 95% of dry weight of RBC and 30% to 34% of wet weight. ā€¢ Function of hemoglobin is to carry the respiratory gases oxygen and carbon dioxide. It also acts as a buffer. ā€¢ Molecular weight of hemoglobin is 68,000.
  • 84. ā€¢ Average hemoglobin (Hb) content in blood is 14 to 16 g/dL. ā€¢ However, the value varies depending upon the age and sex of the individual. ā€¢ Age ā€¢ At birth : 25 g/dL ā€¢ After 3rd month : 20 g/dL ā€¢ After 1 year : 17 g/dL ā€¢ From puberty onwards : 14 to 16 g/dL ā€¢ At the time of birth, hemoglobin content is very high because of increased number of RBCs.
  • 85. ā€¢ Sex ā€¢ In adult males : 15 g/dL ā€¢ In adult females : 14.5 g/dL
  • 86. ā€¢ FUNCTIONS OF HEMOGLOBIN ā€¢ ā€žTRANSPORT OF RESPIRATORY GASES ā€¢ Main function of hemoglobin is the transport of respiratory gases: ā€¢ 1. Oxygen from the lungs to tissues. ā€¢ 2. Carbon dioxide from tissues to lungs. ā€¢ 1. Transport of Oxygen ā€¢ When oxygen binds with hemoglobin, a physical process called oxygenation occurs, resulting in the formation of oxyhemoglobin. The iron remains in ferrous state in this compound. ā€¢ Oxyhemoglobin is an unstable compound and the combination is reversible, i.e. when more oxygen is available, it combines with hemoglobin and whenever oxygen is required, hemoglobin can release oxygen readily
  • 87. ā€¢ Transport of Carbon Dioxide ā€¢ When carbon dioxide binds with hemoglobin, carbhemoglobin is formed. It is also an unstable compound and the combination is reversible, i.e. the carbon dioxide can be released from this compound. The affinity ofhemoglobin for carbon dioxide is 20 times more than that for oxygen
  • 88. ā€¢ BUFFER ACTION ā€¢ Hemoglobin acts as a buffer and plays an important role in acidbase balance
  • 89. ā€¢ STRUCTURE OF HEMOGLOBIN ā€¢ Hemoglobin is a conjugated protein. It consists of a protein combined with an iron containing pigment. The protein part is globin and the ironcontaining pigment is heme. Heme also forms a part of the structure of myoglobin (oxygenbindin pigment in muscles) and neuroglobin (oxygenbinding pigment in brain).
  • 90. ā€¢ IRON ā€¢ Normally, it is present in ferrous (Fe2+) form. It is in unstable or loose form. In some abnormal conditions, the iron is converted into ferric (Fe3+) state, which is a stable form.
  • 91. PORPHYRIN ā€¢ The pigment part of heme is called porphyrin. It is formed by four pyrrole rings (tetrapyrrole) called, I, II, III and IV. The pyrrole rings are attached to one another by methane (CH4) bridges. ā€¢ The iron is attached to ā€˜Nā€™ of each pyrrole ring and ā€˜Nā€™ of globin molecule.
  • 92. ā€¢ GLOBIN ā€¢ Globin contains four polypeptide chains. Among the four polypeptide chains, two are chains and two are Ī±-chains.
  • 93. ā€¢ TYPES OF NORMAL HEMOGLOBIN ā€¢ Hemoglobin is of two types: ā€¢ 1. Adult hemoglobin ā€“ HbA ā€¢ 2. Fetal hemoglobin ā€“ HbF ā€¢ Replacement of fetal hemoglobin by adult hemoglobin starts immediately after birth.
  • 94. ā€¢ It is completed at about 10th to 12th week after birth. Both the types of hemoglobin differ from each other structurally and functionally. ā€¢ Structural Difference ā€¢ In adult hemoglobin, the globin contains two Ī±-chains and two Ī²-chains. In fetal hemoglobin, there are two Ī± chains and two Ī³-chains instead of Ī²-chains.
  • 95. ā€¢ Functional Difference ā€¢ Functionally, fetal hemoglobin has more affinity for oxygen than that of adult hemoglobin. And, the oxygen hemoglobin dissociation curve of fetal blood is shifted to left.
  • 96. ā€¢ ABNORMAL HEMOGLOBIN ā€¢ Abnormal types of hemoglobin or hemoglobin variants are the pathologic mutant forms of hemoglobin. These variants are produced because of structural changes in the polypeptide chains caused by mutation in the genes of the globin chains. Most of the mutations do not produce any serious problem. Occasionally, few mutations result in some disorders. ā€¢ There are two categories of abnormal hemoglobin: ā€¢ 1. Hemoglobinopathies ā€¢ 2. Hemoglobin in thalassemia and related disorders