ANEAMIA DISEASE PHYSIOLOGY AND TREATMENT

PHYSIOLOGY OF ACUTE AND CHRONIC RENAL FAILURE

1. HEMATOLOGICAL DISEASES
BY
Dr. Praveen Kumar Dixit
Associate Professor
KIET School of Pharmacy

2. Hemoglobin (Hb)
Hb is found in RBCs its main function is to transport O
2to tissues.
Structure: 2 parts : heme + globin
Globin: four chains.
Heme: porphyrin ring with central iron. Iron is the site of attachment
with O
2.
There are 4 heme groups, each attached to one globin chain. So one Hb
molecule can carry up to 4 O
2molecules.
According to sequence of amino acids in the primary structure of each
chain, there are four types of chains; α, β, γand δ.

3. Types of Hb:
HbA or HbA1: is the normal Hbin adults represents about 97% of
total Hb. it is composed of 2 αand 2βchains.
HbA2: minor adult Hb, comprised 3% of normal adult Hb. Composed
of 2 αand 2 δchains
HbF(fetal Hb): is the main Hbduring fetal life and about 60% of
normal Hbat birth then disappear gradually. It is composed of 2αand
2 γchains.
HbF has greater affinity for O
2than HbAso ensure O
2transfer from
maternal circulation to fetus RBCs through placenta.

4. Anemia
•Anemiais usually defined as a decrease in the amount ofred blood
cells(RBCs) or the amount ofhemoglobinin thebloodresult in
lowered ability of the blood to carry oxygen.
•SYMPTOMS:
•Low BP
•Fatigue
•Weakness
•Palpitations
•Dizziness

6. Types of Anemia
•Iron deficiency anemia
•Megaloblastic anemia
•Pernicious anemia
•Hemorrhagic anemia
•Hemolytic anemia
•Thalassemia
•Aplastic anemia
•Sickle-cell anemia

7. Iron deficiency anemia
•Inadequate absorption of iron
•Excessive loss of iron
•Increased iron requirement
•Insufficient intake of iron
•Note: Women are at greater risk
(Due to pregnancy or menstrual flow)

8. Megaloblastic anemia
•In red bone marrow production of large,abnormal RBC ie:
Megaloblast
•During normal erythropoiesis, several cell divisions occur and
daughter cells at each stage are smaller than the parent cell.
•But when deficiency of Vitamin-B
12and folic acid occur,the rate of
DNA and RNA synthesis reduced.
•Cell are large and fragile
•Life span 40-50 days
•Depressed production and early lysis causes anemia.

9. Pernicious anemia or Vit-B
12deficiency
anemia
•Intrinsic factor(IF) is needed for absorption of Vit B
12in small intestine.
•Absence of intrinsic factor leads to insufficient absorption of Vit-B12
result in reduced hemopoiesis.
•Its an autoimmune disease in which autoantibodies destroy IF and parietal
cells in the stomach which secrete IF.
•Causes of Vit-B
12deficiency
•Chronic gastritis
•Malignant disease
•Ionizing radiation damage of gastric mucosa

10. Complications
•Subacute degeneration of spinal cord and some nerves of CNS
becomes demyelinated result in partial loss of sensation.
•Note: Vit-B
12is essential for secretion and maintenance of myelin
sheath.

11. Hemorrhagic anemia
•Excessive loss of RBCs through bleeding resulting from large
wounds,stomach ulcers,or heavy menstrual flow.
•Hemolytic anemia
(increased destruction of of RBCs)RBC plasma membrane rupture
prematurely in hemolytic anemia.The released hemoglobin pours into
the plasma and may damage the filtering units(glomeruli) in the
kidney.
Causes:Parasitic toxins
Incompatible transfusion of blood,
Drugs that causes intravascular hemolysis.

12. Aplastic anemia and Hypoplastic anemia
•Both anemias are due to varying degrees of bone marrow failure
•Bone marrow function is reduced in hypoplastic anemia
•Bone marrow function is absent in aplastic anemia
•There is decreased WBC count(leukopenia)
•There is decreased platelets count (Thrombocytopenia)
•Decreased RBC count
Note: when these all three cells are low called Pancytopenia.
Causes:Toxins,Gamma radiation
Cytotoxic drugs,sulphonamides
Malignant diseases,viral diseases(eg: Hepatitis)
Chemicals: Like-benzene

13. Mutations in hemoglobin (hemoglobinopathies:
1-Sicklecellanemia(HbSdisease):
Itisageneticdisorderofbloodcausedbymutationinβ-globinchain
resultingintheformationofHbS.Themutationoccursin6
th
position
ofβ-chainwhereglutamicacidisreplacedbyvaline(nonpolar).Valine
residuesaggregatetogetherbyhydrophobicinteractionsleadingto
precipitationofHbwithinRBCs.RBCsassumesickle-shapedleading
tofragilityoftheirwallsandhighrateofhemolysis.

14. Suchsickledcellsfrequentlyblockflowofbloodinnarrowcapillariesandblockblood
supplytotissue(tissueanoxia)causingpainandcelldeath.
Note:Thelifetimeoferythrocyteinsicklecellislessthan20days,comparedto120
daysfornormalRBCs.
Patientsmaybe:
-Heterozygotes(HbAS):mutationoccursonlyinoneβ-globinchain.Thesepatients
havesicklecelltraitwithnoclinicalsymptomsandcanhavenormallifespan.
Or:Homozygotes(HbSS):mutationoccursinbothβ-globinchainwithapparent
anemiaanditssymptoms
2-HbC disease: Like HbS, HbC is a mutant Hbin which glutamicacid in 6
th
position of
β-chain is replaced by lysine.RBCs will be large oblong and hexagonal.
The heterozygous form (HbAC) is asymptomatic.
The homozygous form (HbCC) causes anemia, tissue anoxia and severe pain.

15. Thalassemia
•A group of hereditary hemolytic anemias
•RBCs are small(microcytic)
•RBCs are pale in colour(hypochromic)
•RBCs are short lived
•Deficient synthesis of hemoglobin occurs in Thalassemia.
•2types of thalassemia (alpha and beta)
•Less alpha chain produced ,called alpha thalassemia
•Less beta chain produced ,called beta thalassemia

16. Sickle cell disease
•The RBCs of a person with sickle-cell disease (SCD) contain Hb-S, an abnormal kind of
hemoglobin. When Hb-S gives up oxygen to the interstitial fluid, it forms long, stiff, rodlike
structures that bend the erythrocyte into a sickle shape .
•The sickled cells rupture easily.
•People with sickle-cell disease always have some degree of anemia.
•Symptoms: Mild jaundice
•joint or bone pain,
•breathlessness, rapid heart rate,
•abdominal pain, fever, and fatigue as a result of tissue damage caused by prolonged recovery
oxygen uptake (oxygen debt).
•Sickle-cell genes are found primarily among populations, or descendants of populations, that live
in the malaria belt around the world, including parts of Mediterranean Europe, sub-Saharan
Africa, and tropical Asia.

17. Hemophilia
•Hemophilia is an inherited deficiency of clotting in which bleeding may occur
spontaneously or after only minor trauma.
•Different types of hemophilia are due to deficiencies of different blood clotting
factors and exhibit varying degrees of severity, ranging from mild to severe bleeding
tendencies.
Eg:
Hemophilia is characterized by spontaneous or traumatic subcutaneous and
intramuscular hemorrhaging, nosebleeds, blood in the urine, and hemorrhages in
joints that produce pain and tissue damage.
•Types:
•Factor –IX-Christmas factor (antihemophilic factor B.)
•Factor-XI -Plasma thromboplastin antecedent (PTA) or antihemophilic factor C.
•Factor -XII-Hageman factor (antihemophilic factor D.)

18. •Anemia is a blood disorder where the body doesn’t have enough
healthy red blood cells or hemoglobin, resulting in poorly
oxygenated tissues throughout the body.
•This condition takes many forms, ranging from mild to severe
depending on the cause.
•Anemia in a man is a hemoglobin below 13.5
g/dL or a hematocrit less than 41%
•In woman it’s a hemoglobin below 12.0 g/dL or
a hematocrit less than 36%
Anemia

23. The hematocrit is a ratio of
the packed cells to total
volume. Example: If the
column of packed red cells
measures 20 mm and the
whole blood column
measures 50 mm, the
hematocrit is 20/50 = 0.4
or (0.4 ×100%) = 40%.

37. •Now, the most common signs and symptoms of anemia are
dyspnea with exertion and at rest, fatigue, and a hyperdynamic
state like bounding pulses and palpitations.
•An MCV of less than 80 is low, so microcytic, between 80 and
100 is normal, so normocytic, and above 100 is high, so
macrocytic.
•Most microcytic and macrocytic anemias are caused by a
problem in producing either red blood cells or hemoglobin.
•In such situations, we measure the reticulocyte
production index (RPI) or corrected reticulocyte
count (CRC). The normal range is between 0.5
and 2.5%.

38. Microcytic anemia
Following Types are there:
•Iron deficiency anemia
•Anemia of inflammation & chronic disease
•Thalassemia.
To distinguish them, iron studies which includes the serum iron, which is the free
iron in the blood, the total iron binding capacity or
TIBC, are carried out. Indicating the unbound
transferrin available to bind iron, the ferritin
level and already bound to iron -effectively
storing it, and a peripheral blood smear.

39. IRON

40. Iron –Basics
•TOTAL BODY IRON CONTENT
•3.5 gm (average): Male-50 mg/kg
•Female –38 mg/kg
•DISTRIBUTION OF IRON IN BODY
•Hb -Protoporphyrin –4 Iron containing haemeresidues
•Loss of 100 ml of blood (15 gm Hb) –50 mg elemental Iron
•To raise Hb level 1 gm/dl –200 mg elemental Iron required
•Stored only in Ferric form (Fe
3+
) –in combination withapoferritin –mainly in RE Cells
•Many cellular enzymes –cytochromes, peroxidases, catalases, xanthine oxidases and some mitochondrial
enzymes contain iron.
•Severe Iron deficiency affects all cells
•Daily requirement: Male: 0.5 to 1 mg/day; Female: 1.5 to 2 mg/day (more in pregnancy) ………… Sources ???
Apoferritn + Fe
3+
 Ferritin
Haemosiderin
aggregates
Haemoglobin- 66%
Store iron as ferritin and
haemosiderin- 25%
Myoglobin- 3%
Parenchymal (enzyme)- 6%

41. Dietary sources of iron
•Rich : Liver, egg yolk, oyster, dry beans,
dry
fruits, wheat germ, yeast.
•Medium : Meat, chicken, fish, spinach,
banana,
apple.
•Poor : Milk and its products, root
vegetables.

42. Iron Absorption
•Diet –10 to 20 mg –absorbed from all over the Intestine (more
from upper part)
•2 forms –haemeandInorganic iron
–Haeme–minor form of dietary Iron but absorbed better without any
transporter (upto35%)
–Inorganic–in ferricform but absorbs lesser –converted to ferrous
form in Intestine for absorption –needs transporter (upto5%)
–Divalent metal transporter (DMT1) and Ferroportin(FP)
•Factors increasingabsorption –acid, reducing substances –
ascorbic acid, amino acid etc. and meat
•Factors impendingabsorption –alkali (antacids), Phosphates,
phytates, tetracycline and presence of other food
•Mucosal block: from mucosal cell –transported to plasma or
remains stored in mucosal cell by forming ferritin-Ferritin
curtain
–Balance between those two –determines how much Iron to enter
body -by haematopoietictranscription factor

43. Iron –Absorption, Transport, storage
Essentials of Medical pharmacology by KD Tripathi –6
th
Edition, JAYPEE,
2008

44. Iron –Transport, storage etc.
•In plasma immediately converted to Fe
3+
form –
complexedwithtransferrin(glycoprotein) (Tf) –Total
Plasma Iron –3 mg –recycled (10 times every day) with
turnover 30 mg/day.
•Transported to RBCs by transferrinreceptors(TfRs) –by
receptor mediated endocytosis–Iron dissociates from TfR
in acidic pH of vesicles
•Iron utilized for Hbsynthesis –TfRsreturn to surface
•In Iron deficiency –TfRsincrease
•Storage –RE cells in Liver, spleen, bone and muscles as
ferritinand haemsiderin
•Apoferritin–determines how much Iron storage needed -
synthesis regulated by Iron status and Iron regulating
element (IRE) on mRNA –blocked in low Iron –no
apoferritinsynthesis
•–in high Iron state –more apoferritinsynthesis
•Excretion –0.5 to 1 mg/day –exfoliation in GI mucosal
cells, RBCs and in Bile …. Also in skin, urine and sweat
•Note: Menstruation loss 0.5-1mg/day

45. 1.IRON DEFICIENCY ANEMIA

46. •Heme iron is in the ferrous, or Fe2+, state. Found in meat
products.
•The other form is non-heme iron, which is free iron molecules
in the ferric, or Fe3+, state. Non-heme iron comes from plant-
based foods like spinach and beans.

47. Iron deficiency anemia can develop as a result of four main causes:
•Decreased intake; Decreased absorption
•Increased demand; Increased iron loss.
•Regardless of the cause, iron deficiency leads to impaired hemoglobin production. Thus,
bone marrow starts pumping out microcytic, or smaller, RBCs.
•These are hypochromic.
•Also called microcytic hypochromic anemia.
•Microcytic RBCs can’t carry enough oxygen to the tissues, and thus cause hypoxia.
Hypoxia signals the bone marrow to increase RBC production.
•As a result, red blood cells of various shapes, called poikilocytosis, and sizes, called
anisocytosis, enter the circulation.
•In addition to anemia, iron deficiency also results in defective
production of mitochondrial enzymes that generate necessary
ATP for growth and development, and this affects fast growing
tissues, like hair and nails, the most.

75. The word “hemophilia” is a combination of the Greek words for
“blood” and “love”, a way of saying that people with hemophilia
“love to bleed”, or rather that it’s hard to stop bleeding.
This is because the process called hemostasis, literally meaning to
stop the flow of blood, is impaired.
In most cases of hemophilia there is a decrease in the amount or
function of one or more of the clotting factors which makes
secondary hemostasis less effective and allows more bleeding to
happen.

76. Now, an insufficient concentration or decreased activity of any
coagulation factor can cause hemophilia, except factor XII
deficiency which is asymptomatic.
Hemophilia usually refers to inherited deficiencies of coagulation
factors, which could be either quantitative or qualitative.

77. •Deficiencies of factor VIII which gives rise to factor VIIIaand is stabilized by another
factor called von Willebrand factor, and this deficiency is called hemophilia A(or
classic hemophilia).
•Another common deficiency is deficiency of factor IX, called hemophilia B(which used
to be called Christmas disease, named after the first patient who had it, not the
holiday).
•A mimic of hemophilia A is von Willebrand disease, which is an inherited problem
with primary hemostasis caused by a deficiency of von Willebrand factor. So, in severe
von Willebrand factor deficiency, factor VIII gets broken down faster and can become
deficient, too.
•As opposed to inherited forms of hemophilia, one acquired causes of hemophilia is
liver failure since the liver synthesizes factors I, II, V, VII, VIII, IX, X, XI, and XIII.
•Also, vitamin K deficiency can cause hemophilia, since vitamin
K is needed by the liver to synthesize and release factors II,
VII, IX, and X.
•Another cause is autoimmunity against a clotting factor, and
finally there’s disseminated intravascular coagulation which
consumes coagulation factors.

78. Thank
You