Blood Biochemistry BCH 577 Prof. Omar S. Al-Attas Professor of
Biochemistry Biochemistry Department King Saud University Slide 2
Chapter 1 Slide 3 Introduction To Hematology Blood is the only
tissue that flows throughout your body. This red liquid carries
oxygen and nutrients to all parts of the body and waste products
back to your lungs, kidneys and liver for disposal. It is also an
essential part of your immune system, crucial to fluid and
temperature balance, a hydraulic fluid for certain functions and a
highway for hormonal messages. It represent about 8% of total body
weight Average volume of 5 liters in women Average volume 5.6
liters in men 99% of blood cells are erythrocytes Plasma accounts
for the remaining of the blood volume. Consist of three types of
cellular elements (Erythrocytes, Leukocytes and Platelets) The
cellular elements are suspended in plasma Slide 4 Hematopoiesis The
cells normally found in the circulatory blood are of three main
types: The erythrocytes ( RBC) are largely concerned with oxygen
transport. The leukocytes (White blood cell) play various roles in
defense against infections and tissue injury. The thrombocytes
(platelets) are immediately involved in maintaining the integrity
of blood vessels and in the prevention of blood clots Hematopoiesis
(poiesis= formation) Is the term used to describe the formation and
development of blood cells. Cellular proliferation, differentiation
and maturation take place in the hematopoietic tissue, which
consists primarily of the bone marrow. Only mature cells are
released to the peripheral blood. Hematopoietic begins in the
nineteenth day after fertilization in the yolk sac of human embryo.
Then the fetal liver becomes the chief site of blood cell
production( at about this time the yolk sac discontinues its role
in the hematopoiesis. Also at this time hematopoiesis also begins
to lesser degree in the spleen, kidney, thymus and lymph nodes. At
about 4-5 months of gestation hematopoiesis commences in the bone
marrow where it is fully active by the seventh or eight month and
at birth partially the whole bony skeleton contain active marrows.
During childhood and adolescence there is a marked recession of
marrow activity in the long bones so that in the adult activity is
limited to the trunkcal skeleton and skull. Slide 5 Slide 6 Site of
Hematopoiesis Slide 7 Slide 8 Cont In the yolk sac, most of
hematopoiesis activity at this site is confined to erythropoiesis
(erythrocytes formation). Cell production at this site time is
called Primitive erythropoiesis because this erythroblast and Hb
are not typical of that seen in later developing erythroblasts
Hematopoiesis in the bone marrow is called medullary hematopoiesis.
Slide 9 Hematopoietic Tissues 1. Spleen, is located in the upper
left quadrant of the diaphragm (muscle near the stomach) It is
enclosed by capsule of connective tissue which contains the largest
collection of lymphocytes and mononuclear phagocytes in the body.
Splenic function: Immune defense Culling(The removal of aging or
abnormal red blood cells) Pitting (The ability of the spleen to
clear inclusions while maintaining the integrity of the red cell)
Slide 10 Culling The discriminatory filtering and destruction of
senescent or damaged red cells by the spleen ATP is important in
cation pump of erythrocytes and because of entering the spleen
through the slow transit become concentrated in the hypoglycemic
due to low concentration of glucose and slow circulation in the
splenic cords, the supply of glucose in the damaged or senescent
erythrocytes is rapidly diminished. This decrease the availability
of ATP and contributes to the demise of these red cells. Slow
passage through a macrophage-rich route before allows the
phagocytic cells to remove these old or damaged erythrocyte before
or during their squeeze through 3m pores to cords and sinuses.
Normal RBC withstand this adverse environment and eventually
reenter the circulation. Slide 11 Cont Pitting The spleens ability
to pluck out particles from intact erythrocytes. The pinched off
cell membrane can reseal itself, but the cell cannot synthesize
lipids and proteins for new membrane because of its lack of
cellular organelles. Therefore extensive pitting causes reduced
surface- area to volume ratio resulting in the formation of
spherocytes. Slide 12 For Example: Howell Jolly Bodies: Small,
round or oval structure pinkish or bluish in color, observed in
erythrocytes in various anemias and leukemias and after
splenectomy, they also represent unphysiological red cell nuclear
remnant. Pappenheimer Bodies: Basophilic containing iron granules
observed in various types of erythrocytes Heinz bodies: Resulting
from oxidative injury to unprecipitation of Hb (abnormal Hb) and
also erythrocytes with enzyme deficiency. Blood cells coated with
Ab are also susceptible to pitting by macrophages. The macrophage
removes the antigen-antibody complex and the attached membranes.
The presence of spherocytes on a blood film is evidence that the
red blood cells has undergone membrane assault in the spleen. Slide
13 Inclusion Bodies Pappenheimer bodies Slide 14 Cont Defense
Spleen is rich supply of lymphocytes and phagocytic cells as well
as its unique circulation Reservoir for platelets Massive
splenomegaly may result in pooling of 80-90% of the platelets
producing peripheral blood thrombocytopenia. Condition associated
with an enlargement of the spleen are also frequently accompanied
by leukopenia and anemia, the result of splenic pooling and
sequestration Removal of the spleen results in transient
thrombocytosis, with the platelet count returning to normal in
about 10 days. Splenectomy does produce characteristic erythrocyte
abnormalities that are easily noted on blood smears by experienced
technologist. After splenectomy, the red cells contain granular
inclusion such as Howell- jolly bodies, pappenheimer bodies. Target
cells, cells with excess membrane to volume ratio, have several
mechanism of formation The splenectomized patients, these cells are
probably formed as a result of excess lipid on the membrane since
the missing spleen would normally have groomed the excess lipid
from reticulocytes in their maturation process. Slide 15
Hypersplenism Under certain conditions the spleen may become
enlarged; consequently exaggeration of its normal filtering and
phagocytizing. So anemia leukopenia, thrombocytopenia, then plasma
volume increases consequently cytopenias occurs. A diagnosis of
hypersplenism is made when four conditions are met: 1. Anemia,
leukopenia or thrombocytopenia in the blood. 2. 2. Cellular or
hyperplastic bone marrow ( increase in normal cells of the
tissue)corresponding to the peripheral blood cytopenias. 3. The
occurrence of the splenomegaly 4. 4. The correction of cytopenia as
following splenectomy. Slide 16 Hypersplenism Primary Occurs when
no underlying cause identified. The spleen behaves normal but
causes disease. The most common cause is congestive splenomegaly
associated with liver cirrhosis and portal hypertension. Thrombosis
of the splenic or portal veins may contribute Secondary Caused by a
disorder. The causes: Inflammatory and infectious diseases increase
the defense function of the spleen. Gauchers disease- macrophages
accumulates large quantities of undigestable substance causes
splenomegaly Slide 17 Lymphnodes The lymphatic system is composed
of lymph node (bean-shaped) 2. Lymph Vessels: Node are composed of
lymphocytes, macrophages and reticular meshwork. The morphology:
lymph nodes contain the following: an inner area called medulla,
outer area called cortex. The medulla: surround the efferent
lymphatics and contains the B lymphocytes The cortex contains the
T-lymphocytes The lymph nodes act as filter removing foreign
particles from the lymph by phagocytic cells. Antigens pass through
the nodes, they contact and stimulate immune complex lymphocytes to
proliferate and differentiate into effector cells Slide 18 Thymus
3. Thymus The thymus is a well developed organ at birth and
continues to increase in size until puberty, and eventually would
begin to atrophy ( hardening). It is bilobular organ packed with
small lymphocytes and a few macrophages. Thymus is to serve for
maturation of T-lymphocytes. The thymic hormone, thymosin, is
important in the maturation of virgin lymphocytes into
immunocompetent T-cells. Slide 19 Bone Marrow 4. Bone Marrow In
adult the marrow normally consist of islands of cellular active
marrow separated and supported by fat (Yellow fat). Red marrow
contains both erythroid and myeloid precursors with ration of (M:E)
of 1.5:1 to 4:1 For the first four years of life nearly all marrow
cavities are composed of red hematopoietic marrow. After 4 years of
age, the red marrow in shafts of long bones is gradually replaced
by yellow fat tissues. Slide 20 The Assessment of Marrow Activities
In general if a patient has a normal peripheral blood count and a
bone marrow aspirate contains what appears to be adequate number of
cells, present in normal proportions it is reasonable to assume
normal activity Cellular or even hypercellular marrow may be
associated markedly defective output of cells to the peripheral
circulation: e.g. megaloblast anemia is featured by excessive
cellular destruction in the marrow itself. Other cases a defective
peripheral cell count may be associated with hypercellular marrows,
there being excessive destruction of cells in the circulation or
sequestration in an enlarged spleen. Slide 21 Chapter 2 Slide 22
Derivation of Blood Cells Replacement of effete peripheral
hematopoietic cells is the function of more primitive elements in
the bone marrow called stem cells. Stem cells are characterize by:
Ability to differentiate into distinct cells lines with specialize
functions. Ability to regenerate themselves in order to maintain
the stem cell compartment. Slide 23 Slide 24 Cont Myeloblasts and
erythroblasts (pronormoblasts) because of the high mitotic index,
were believed to responsible for maintaining normal numbers of
mature blood cells. But these two types of cells have limited
ability to proliferate into the billions of blood cells replaced
daily. So two different theories on stem cells have been proposed
to verify the existence of stem cell different from myeloblasts and
erythroblasts. 1. Monophyletic theory: Pluripotential stem cell
under unknown hormonal factors may give rise to each of the
principle blood cell lines. These pluripotential cells have the
capability to self-renewal, proliferation and differentiation into
all hematopoietic cells lines. 2.Polyphylitic theory. Each blood
cell type come from a separate stem cell. So each monopotential
stem cell differentiates into only one type of blood cell. Slide 25
Cont (Erythrocytic, myelocytic or megakaryocytic) It has been
suggested that nodules appearing at 7 th days were formed from more
mature unipotent committed stem cells In the day 14 the nodules
showed mixed cell populations. The cell that formed colony termed-
Colony-forming unit spleen (CFU-S) Suggesting the nodules at this
time were derived from more primitive multipotential stem cell.
Stem cells number one per 1000 nucleated cells in the marrows Slide
26 Erythropoiesis 0 The earliest recognizable erythroid cells in
the bone marrow is the pronormoblast which is a long cell measuring
15-20 m in diameter. With dark blue cytoplasmin, a central rounded
nucleus with nucleoli and slightly clumped chromatin. The deep
color of the more immature cells due to the presence of large
amount of RNS which is associated with active protein synthesis. 0
They also contain Hb (which stain pink) in the cytoplasm; the
cytoplasm stain pale blue as it does its RNS and protein synthetic
apparatus while the nuclear chromatin becomes more condensed. 0 Any
remaining nuclear material is removed by a process of pitting
during passage through the splenic sinus walls. 0 The successive
cytoplasmic charge from blue to pink earning them name basophilic,
polychromatic and orthochromatic 0 After extruding the nucleus from
the normoblast the new stage of cells is called reticulocytes which
still contain some ribosomal RNA and still able to synthesis Hb.
This cell spends 1-2 days in the bone marrow and also circulates in
the peripheral blood for 1-2 days before maturing mainly in the
spleen when RNS is completely lost and completely pink-staining
mature erythrocytes (red cell). Slide 27 Kinetics of Erythropoiesis
In man, time required for erythropoiesis to proceed from the
undifferentiated stem cell to reticulocyte is about 7 days and the
final maturation of these cells in the peripheral blood and spleen
takes about 24 hours This means that some 210 thousand million
erythrocytes must be produced by the marrow each day about 9
thousand million per hour. This requires the synthesis of 6.5g Hb
and involves the turnover of about 22mg of iron. To maintain
regular erythropoiesis 1. Erythropoietin- the principle site of
erythropoietin production in the kidney. Erythropoiesis is
regulated by hormone erythropoietin which: Acts primarily on more
mature committed erythroid cells of erythroid colony- forming
units. Increasing Hb synthesis in red cells precursors. Decreasing
maturation time of red cell precursors. Releasing marrow
reticulocytes into peripheral blood at an earlier stage than
normal. Slide 28 Cont 2. For normal erythropoiesis to be
established there must be adequate supply of stem cells in a
satisfactory environment containing all the essential materials for
their normal growth and differentiation. The materials include
beside those require by all cells certain specific factors: Vit
B12, folate, Vit C, Vit E, Vit B6, pyroxidine, thiamine,
riboflavin. Metal: Iron, manganese, cobalt Amino acids Hormone:
erythropoeitin, thyroxine and androgens Slide 29 Erythrocytes The
mature erythrocytes of the peripheral blood of a man are:
Non-nucleated and contain organelles Contain enzyme of both
anearobic glycolytic pathway of Embden-Myerhoff and aerobic pentose
P pathway It stains pink to orange because of the large amount
intracellular acidophilic protein called Hb. The 7 m RBC must be
flexible corpuscle to squeeze through the tiny 3 m fenestrations of
the capillaries of the spleen. Slide 30 Erythrocytes Membrane The
cells flexibility is a property of both the erythrocyte membrane
and the fluidity of the cells content which is main hemoglobin. It
is a biphospholipid protein composed of the following: 49 % protein
(composed of contractile protein, enzyme, surface antigens) 43%
lipid (95% of lipid is equal amounts of unspecified cholesterol and
phospholipids. The remaining are glycolipids. The polar lipids on
the external and internal surfaces and non polar at the center of
the membrane. 8% CHO ( occurs on the external surface) Slide 31
Slide 32 Cont Cholesterol responsible for the passive cation
permeability if the membrane. It appears that membrane cholesterol
exist in free equilibrium with plasma cholesterol. Increase
cholesterol in plasma (such as occur in lecithin-cholesterol
acyltransferase LCAT deficiency) results in accumulation of
cholesterol on membrane. These cholesterol laden erythrocytes
appears distorted with formation of target cells and spicules (tiny
spike-like structure) Increase in cholesterol: Phospholipids
increases the microviscosity and the degree of order of the
membrane. The phospholipids are: Phosphatidylethanolamine
(Cephalin) Phosphatidylcholin (Lecithin) Sphengomyelin
Phosphatidylserine Slide 33 Cont Glycolipids is in the form of
glycosphingolipids (cerebrosides and gangliosides) are responsible
for some antigenic properties of the membrane in particular those
coresponding to the A,B, H and lewis blood groups. Glycoprotien
have similar antigenic properties. Proteins in the membrane Two
types (both synthesized during cell development) Integral protein
consist of two types: Glycophorin A and band 3. Glycophorin A
serves as receptors for certain viruses and lectins. Band 3 (the
name is from its migration with erythrocyte proteins on SDS
polyacrylamide gel electrophoresis. It is responsible for an ion
transport across the membrane. Peripheral proteins lack CHO
moieties and are to the cytoplasmic side of the lipid bilipid layer
These proteins include: Enzyme glycealdehyde-3-p dehydrogenase.
Skeletal proteins e.g. spectrin actin viscoelastic properties and
contribute to cell shape deformability and membrane stability.
Calcium is a membrane component. 80% of intracellular calcium is
found in membrane. It is maintained at an extremely low
intracellular concentration by the activity of an ATP pump. The
accumulation of calcium cation induces irreversible cross-linking
and alteration of cytoskeletal proteins. Slide 34 Erythrocyte
Metabolism Although the binding, transport and release of oxygen
and carbon dioxide is a passive process not requiring energy, a
variety of energy- dependent metabolic processes occur that are
essential to cell viability. The metabolism of the red cell is
limited because of the absence of a nucleus, mitochondria and other
subcellular organelles. The most important metabolic pathway in the
mature erythrocytes require glucose as substrate. Slide 35
Metabolic Pathways These pathways include: a. Embden-Meyerhof
pathway b. Hexose-monophosphate (HMP) shunt c. Methemoglobin
reductase pathway d. Rapoport-leubering pathway These pathways
contribute: The first pathway for providing energy for maintaining
high intracelllur K +, low intracellular Na + and very low Ca 2+
(cation pump) The second pathway provides reducing power to protect
Hb in reducing state. The third pathway regulates oxygen affinity
of Hb Maintains Hb in reduced state Slide 36 Embden-Meyerhof
Pathway 90-95% of the red cells glucose consumption is utilized by
this pathway. Normal red cells have glycogen deposits. They depend
entirely on environmental glucose for glycolysis. Glucose enters
the cell by the facilitated diffusion an energy-free process. ATPs
Are necessary to maintain red cell shape and flexibility. Membrane
integrity through regulation of intracellular cation concentration:
Na + & Ca 2+ are more concentrated in the plasma. K + is more
concentrated within the cell. Erythrocyte osmotic equilibrium is
maintained by: The selective permeability of the membrane By the
cation pumps located in the cell membrane Slide 37 Cont The Na +
& K + pump ADP + Pi In the expulsion of 3 Na + and the uptake
of 2K +. Ca 2+ is maintained in low concentration by the action of
a similar but separate cation pump that utilized ATP for fuel.
Excess leakage of Ca 2+ into the cell or failure of the pump causes
rigid shrunken cells with protrusions (echinocytes) An increase in
calcium is associated with excess K + leakage from cell. Magnesium
is another major intracellular cation. It reacts with ATP to form
the substrate complex, Mg-ATP for Ca 2+ - MgCT- ATPase (calcium
cation pump). Upon the exhaustion of glucose, the fuel for the
cation pumps is no longer available. Cells cannot maintain normal
intracellular cation concentrations and this leads to cell death
hydrolysis One ATP Slide 38 Hexose Monophosphate Shunt (HMP shunt)
5% of cellular glucose enters the oxidative HMP shunt, an ancillary
aerobic energy system. In the pathway glucose-6- P is converted to
6-phosphogluconate and so to ribulose-5- P. NADPH is generated and
is linked with GSH which maintains sulfhydryl (-SH) groups intact
in the cell including those in Hb and RBC membrane. Reduced
glutathione (GSH) protects the cell from permanent oxidant injury
(H 2 O 2 ). Oxidants, within the cell will oxidize Hb-SH groups,
unless they are reduced by glutathione. This reduction oxidizes
glutathione (GSSG), which in turn is reduced by adequate levels of
NADPH. The red cell normally maintains a large ratio of NADPH to
NADP +. Failure to maintain reducing power through levels of GSH or
NADPH leads to oxidation of Hb - SH groups, followed by
denaturation and precipitation of Hb in the form of Heinz bodies.
Heinz bodies with a portion of the membrane are then plucked out by
the macrophages of the spleen. Reduced GSH is also responsible for
maintaining reduced-SH groups at the membrane level. Decrease of
GSH lead to injury of membrane sulfhydryl groups resulting in leak
of cell membrane. Slide 39 Methemoglobin Reductase Pathway The
methemoglobin reductase pathway, an offshoot of the Embden-Meyerhof
pathway, is essential to maintain heme iron in the reduced state,
Fe++ Hemoglobin with iron in the ferric state Fe ++ is known as
methoglobin. This form of Hb cannot combine with O 2 Methemoglobin
reductase together with NADPH produced by the Embden-Meyerhof
pathway protect the heme iron from oxidation. The absence of this
system, the 2% of heme methemoglobin formed daily will eventually
raise to 20-40% surely limiting the oxygen-carrying capacity of the
blood. Slide 40 Rapoport-Luebering Pathway The Rapoport-Luebering
Pathway is a shunt of Embden- Meyerhof pathway. DPG is present in
the erythrocytes in a conclusion of 1,ol DPG/ 1 mol Hb, and it
binds exclusively to deoxyHb. As more DPG binds to deoxy Hb,
glycolysis is stimulated to produce more DPG and ATP. Increase in
DPG concentration facilitate the release of O 2 to the tissues by
causing a decrease in Hb affinity for oxygen. Thus, the red cell
has built-in mechanism for regulation of O 2 delivery to the
tissues Slide 41 Slide 42 Hexose monophophate shunt pathway Slide
43 Chapter 3 Slide 44 Lifespan and Faith of RBC 0 Normally, the
average life span of red blood cells is 120 days. This cells live
in blood circulation. 0 In in typical adult produces 200 billion
RBC per day. 0 At the end of their lifespan, they become senescent,
and are removed from circulation. 0 In many chronic diseases, the
lifespan of the erythrocytes is markedly reduced (e.g. patients
requiring haemodialysis). 0 The destruction of RBC is about 2-3
million per second on average. Causes of reduction in the life span
of RBC. 1. Defects in RBC (curpuscular defects) e.g. Hereditary
spherocytosis Sickle cell anemia, Thalassemias 2.Deficiency of red
cell enzyme such as: G6PD, Pyruvate kinase def., Autoimmune
disorder, Hypersplenism Slide 45 Cont The fate of the RBC 0 After
120 days, the RBC becomes more fragile due to decrease NADPH
activity. 0 Younger RBC RBCs can easily pass through the
capillaries which have the diameter smaller than the mature RBCc 0
With a fragile membrane, the mature RBC are destroyed while trying
to squeeze through capillaries. 0 The destruction most occurs in
the capillaries of the spleen. This is why spleen is called the
grave yard of the RBC. 0 The hemoglobin is released and taken up
the macropharges Pathway of RBC destruction Slide 46 Cont Slide 47
Bilirubin 0 Is the yellow breakdown product of normal heme
catabolism. 0 Bilirubin is excreted in bile and urine, and elevated
levels may indicate certain diseases. 0 It is a toxic waste product
in the body 0 It is extracted and biotransformed mainly in the
liver and excreted in bile and liver. 0 Elevation in serum and
urine bilirubin is associated with juandice Slide 48 Slide 49 Slide
50 Slide 51 In Blood 0 The bilirubin synthesized in spleen, liver
and bone marrow is unconjugated bilirubin 0 It is hydrophobic in
nature so it is transported to the liver as complex with the plasma
protein, albumin Unconjugated bilirubin(Free Bilirubin) 0 Lipid
soluble 0 1gm albumin binds 8.5 mg of bilirubin 0 Fatty acids and
drugs can displace bilirubin 0 Indirect positive reaction in van
den Berg test Slide 52 0 Conjugated (Direct) bilirubin is released
into the bile by the liver and stored in the gallbladder, or
transferred directly to the small intestines. 0 Bilirubin is
further broken down by bacteria in the intestines, and those
breakdown products contribute to the color of the feces. 0 A small
percentage of these breakdown compounds are taken in again by the
body, and eventually appear in the urine 0 Unconjugated (indirect)
Erythrocytes generated in the bone marrow are disposed of in the
spleen when they get old or damaged. 0 This releases hemoglobin,
which is broken down to heme as the globin parts are turned into
amino acids. 0 The heme is then turned into unconjugated bilirubin
in the reticuloendothelial cells of the spleen. 0 This unconjugated
bilirubin is not soluble in water, due to intramolecular hydrogen
bonding. It is then bound to albumin and sent to the liver. Slide
53 Jaundice Slide 54 Slide 55 Slide 56 Slide 57 Slide 58 Slide 59
Slide 60 Slide 61 Treatment for Neonatal Jaundice Slide 62 Slide 63
Bilirubin Lab values Bilirubin formNormal value Total (elderly,
adult, child) (newborn) Critical value (a(newborn) 0.1 to 1.0 mg/dL
1.0 to 12.0 mg/dL >12 mg/dL >15 mg/dL Pre-hepatic,
unconjugated, indirect0.0 to 0.8 mg/dL Post-hepatic, conjugated,
direct0.0 to 0.25 mg/dL Fecal urobilinogen40 to 280 mg/day Urine0.0
to 0.02 mg/dL Conjugated bilirubin - water soluble - direct
reaction with dyes Unconjugated bilirubin - water insoluble -
alcohol is needed for dye (indirect) reaction Observe the color
changes associated with heme degradation by watching the progress
of a bruise (dark red to green to yellow). Slide 64 Chapter 4 Slide
65 Classification of anemia Morphologic 0 Normocytic: MCV= 80-100fL
0 Macrocytic: MCV > 100 fL 0 Microcytic : MCV < 80 fL
Pathogenic (underlying mechanism) 0 Blood loss (bleeding) 0
Decreased RBC production 0 Increased RBC destruction/pooling Slide
66 Other causes: Inadequate production of mature red cells 1.
Deficiency of essential substances like iron, folic acid, vit B12,
protein and other elements like copper, cobalt, etc. 2. Deficiency
of erythroblast.. i.e.Aplastic (anemia body's bone marrow does not
make enough new blood cells.), Pure red cell aplasia 3.
Infiltration of the bone marrow i.e. leukemia, lymphoma, carcinoma,
myelofibrosis 4. Endocrine abnormalities i.e. myxedema, Addison's
disease, pituitary insufficiency 5. Chronic renal disease 6.
Chronic inflammatory disease 7. Cirrhosis of liver Pure red cell
aplasia (PRCA) is an uncommon disorder in which maturation arrest
occurs in the formation of erythrocytes. * Pure red cell aplasia
(PRCA) is an uncommon disorder in which maturation arrest occurs in
the formation of erythrocytes. Slide 67 The etiologic possibilities
are Iron deficiency Thalassemia Sideroblastic anemia (abnormal
normoblasts with excessive accumulation of iron in the
mitochondria) Anemias of chronic disease. Severe microcytic anemia
(MCVSlide 68 Macrocytic Anemia Normocytic Anemias Megaloblastic
anemias Vit.B12 def. - (1) pernicious anemia (2) malabsorption
Folate def. - (1) malnutrition (2) malabsorption (3) chronic
hemolysis (4)drugs - phenytoin, sulfa Hemolysis Myelodysplastic
syndrome ( A group of conditions that occur when the blood-forming
cells in the bone marrow are damaged. This damage leads to low
numbers of one or more types of blood cells.) Marrow failure -
Aplastic anemia Chronic liver disease Hypothyroidism Macrocytic
anemia may be the result of megaloblastic (folate or vitamin B12
deficiency) or nonmegaloblastic causes. Folate deficiency can in
turn be due to either reduced intake or diminished absorption.
Severe macrocytic anemia (MCV >125 fL) is almost always
megaloblastic. These may be classified as follows: underproduction
of erythrocytes due to (1) the anemia of chronic disease (2) marrow
failure (3) renal failure (decreased erythropoietin) loss or
destruction of erythrocytes due to (1) hemolysis (2) acute blood
loss The causes of normocytic anemias include aplastic anemia,
bone-marrow replacement, pure red-cell aplasia, anemias of chronic
disease, hemolytic anemia, and recent blood loss. A number of
anemias have a genetic etiology. Examples of such inherited
disorders include hereditary spherocytosis, sickle-cell (SC)
anemia, and thalassemia Slide 69 Iron Deficiency Anemia 0 It is a
condition when supply of iron in the body to bone marrow falls
short of that required for the production of red blood cells. It is
the commonest cause of anemia throughout the world. 0 The incidence
of anemia in the general population is about 1.5%. 0 Iron
deficiency related to inadequate replacement of lost iron is the
most frequent cause of asymptomatic anemia and has a variety of
causes. 0 Iron deficiency is common among women of childbearing
age; 10% to 20% of menstruating women have abnormally low
concentrations of hemoglobin (usually
