NOMAD:2006: BP: HBANEM 1

HEMOGLOBIN &
ANEMIAS
By
Dr.M.Anthony David MD
Professor of Physiology

NOMAD:2006: BP: HBANEM 2

 HEMOGLOBIN
 A CHROMO PROTEIN MOLECULE.
 IS PRESENT EXCLUSIVELY
WITHIN THE ERYTHROCYTE.
 ROUGHLY ONE THIRD OF THE
VOLUME OF THE ERYTHROCYTE
IS OCCUPIED BY HEMOGLOBIN.
 IS A COMPLEX PROTEIN WITH
TWO MOIETIES: HEME + GLOBIN.
NOMAD:2006: BP: HBANEM 3
HEMOGLOBIN MOLECULE

NOMAD:2006: BP: HBANEM 4

 SYNTHESIS OF HEMOGLOBIN

 REQUIRES:
 Nutrients such as Proteins,
Vitamins & Minerals.
 TAKES PLACE ONLY WITHIN THE
NORMOBLASTCELLS.(INTRACELLUL
AR)
 HEMOGLOBIN = HEME + GLOBIN
 HEME = PIGMENT
 GLOBIN = PROTEIN
NOMAD:2006: BP: HBANEM 5
 HEME
 Iron containing Porphyrin.
 Iron-Protoporphyrin IX
 Porphyrin is formed from 4
Pyrrole rings joined by four
methane bridges.
 The side chains 1,3 5, & 8 are
Methyl.
 The side chains 2 & 4 are Vinyl.
 The side chains
NOMAD:2006: 6 & 7 are
BP: HBANEM 6
NOMAD:2006: BP: HBANEM 7
HEMOGLOBIN CATABOLISM
 Macrophages, mainly the Kupffer cells
in the liver phagocytose Hemoglobin.
 HEMOGLOBIN = HEME + GLOBIN

HEME Fe++ + PORPHYRIN

PORPHYRIN BILVERDIN + CO.
CO TO THE LUNGS AND OUT.
BILVERDIN REDUCED TO BILIRUBIN AND
SENT TO BLOOD & LIVER FOR
EXCRETION. NOMAD:2006: BP: HBANEM 8
HEMOGLOBIN CATABOLISM

Fe++ + TRANSFERRIN TO BONE

MARROW FOR REUSE.
Fe++ + PORPHYRIN HEME
(In the presence of the enzyme,
Heme Oxidase.)
 HEME + GLOBIN HEMOGLOBIN

NOMAD:2006: BP: HBANEM 9

HEMOGLOBIN:NORMAL
LEVELS
 MALES: 14 – 18 Gm%
 FEMALES: 12 – 15 Gm%
 AT BIRTH: 23 Gm%
 FALLS TO 10.5Gm% BY THIRD
MONTH
 RISES GRADUALLY TO 12.5
Gm% AT 1 YEAR OF AGE.
NOMAD:2006: BP: HBANEM 10
 HEMOGLOBIN LEVELS :
SIGNIFICANCE
 1 Gm OF HEMOGLOBIN, WHEN
FULLY SATURATED, COMBINES
WITH 1.34 ml OF OXYGEN.

 HEMOGLOBIN CONCENTRATION
IS THEREFORE AN INDEX OF THE
OXYGEN CARRYING CAPACITY OF
THE BLOOD.
NOMAD:2006: BP: HBANEM 11
HEMOGLOBIN FORMATION:
FACTORS
1. PROTEINS:
 HIGH POTENCY: ANIMAL

PROTEINS LIKE LIVER,

SPLEEN KIDNEY & HEART
MOST POTENT
 MUSCLE PROTEINS MEDIUM

POTENT
 LEAST POTENCY: CEREALS,

DAIRY PRODUCTS,
VEGETABLES &HBANEM
NOMAD:2006: BP: FRUITS 12
HEMOGLOBIN FORMATION:
FACTORS
2. IRON: HEMOGLOBIN HAS 2.5
Gms OF THE TOTAL BODY
IRON OF 4 - 5 Gms IN AN
AVERAGE HEALTHY ADULT.

NOMAD:2006: BP: HBANEM 13

 HEMOGLOBIN: STRUCTURE
 HAS FOUR POLYPEPTIDE CHAINS OF
TWO TYPES: EACH IN DUPLICATE.
 HbA: ADULT HEMOGLOBIN HAS:
 2 α CHAINS AND
 2 β CHAINS.
 EACH CHAIN IS ASSOCIATED WITH
ONE HEME GROUP.
 THUS THERE ARE FOUR HEMES TO
THE MOLECULE, A TETRAMER OF MW
68,000 NOMAD:2006: BP: HBANEM 14
STRUCTURE & FUNCTION
 Hb A = α2 β2

 HEMOGLOBIN COMBINES LOOSELY &

REVERSIBLY WITH OXYGEN.
 IT’S AFFINITY TO OXYGEN IS
DECREASED IN THE PRESENCE OF
2,3, DIPHOSPHO GLYCERATE (2,3
DPG)
 2,3 DPG IS A PRODUCT OF GLUCOSE
METABOLISM. NOMAD:2006: BP: HBANEM 15
STRUCTURE & FUNCTION
  2,3 DPG AFFINITY OF Hb
TO O2
 THIS CAUSES THE OXYGEN TO BE
FREELY DISSOCIATED.
 THIS HAPPENS AT THE TISSUE
LEVEL.
 ENSURES FREE AVAILABLITY OF
O2 TO THE TISSUES.
 THUS OXYGEN DELIVERY IS A
BASIC FUNCTION
NOMAD:2006: BP: OF
HBANEM 16
 HEMOGLOBIN: VARIETIES
 HEME IS THE SAME
 VARIETIES ARE DUE TO CHANGES

IN THE PEPTIDES OF THE GLOBIN

MOIETY.
 PHYSIOLOGICAL VARIETIES:

1. ADULT Hb: Hb A:
 Hb A: α2 β2: PREPONDERANT FORM:
68,000
 Hb A2: α2 δ2 : A MINOR COMPONENT
NOMAD:2006: BP: HBANEM 17
 Hb:PHYSIOLOGICAL
VARIETIES

2. FETAL HEMOGLOBIN:
 Hb F : α γ
2 2
 γ : GAMMA CHAINS HAVE MORE
AFFINITY TO OXYGEN.
 THIS HELPS THE FETUS TO
ACQUIRE OXYGEN FROM THE
MOTHER.
NOMAD:2006: BP: HBANEM 18
 Hb: PATHOLOGICAL :
SICKLE CELL DISEASE
 CAUSE:
 ABNORMAL POLYPEPTIDES DUE TO

SUBSTITUTION OF AMINO ACIDS

 SUPRESSION OF SYNTHESIS OF

POLYPEPTIDE CHAINS.
 Hb S:
 OCCURS IN 0.3 to 1 % OF WEST

AFRICAN & AMERICAN BLACK

PEOPLE
 VALINE IS SUBSTITUTED FOR
GLUTAMIC ACID AT 6 POSITION OF
BETA CHAIN.NOMAD:2006: BP: HBANEM 19
NOMAD:2006: BP: HBANEM 20
 SICKLE CELL DISEASE
 WHEN Hb S IS REDUCED, IT
BECOMES LESS SOLUBLE & ‘GELS’
 THIS CHANGES THE SHAPE OF THE
ERYTHROCYTES.
 THEY BECOME ‘SICKLE’ SHAPED
 THEY INCREASE THE BLOOD
VISCOSITY AND UNDERGO
HEMOLYSIS.
 THIS IS A SERIOUS CONDITION, CAN
BE FATAL BYNOMAD:2006:
MIDDLE AGE.
BP: HBANEM 21
A SICKLED ERYTHROCYTE

NOMAD:2006: BP: HBANEM 22

 Hb: PATHOLOGICAL :
THALASSEMIAS
 DEFECT IN THE SYNTHESIS OF
EITHER ALPHA & BETA CHAINS OF
GLOBIN.
 OCCURS IN HOMOZYGOUS
OFFSPRING OF HETEROZYGOUS
PARENTS.
 BETA THALASSEMIA IS MORE
COMMON. BETA CHAIN NOT FORMED.
NOMAD:2006: BP: HBANEM 23
 BETA THALASSEMIA
 ERYTHROCYTES ARE ABNORMAL:
HAVE LESS Hb A AND MORE OF
Hb A2 & Hb F.
 RAPID HEMOLYSIS OCCURS IN
VIVO.
 CAUSES HYPOCHROMIC ANEMIA.
 CHILDREN FAIL TO THRIVE.
 THEY DIE YOUNG.
NOMAD:2006: BP: HBANEM 24
NOMAD:2006: BP: HBANEM 25
NOMAD:2006: BP: HBANEM 26
IRON METABOLISM
& ANEMIAS
By
Dr.M.ANTHONY DAVID, MD
Professor of Physiology

NOMAD:2006: BP: HBANEM 27

 IRON IN THE BODY
BIOCHEMICAL SITE CONC. % OF
FORM TOTAL
HEMOGLOBIN Erythrocytes 2.5 Gms 60-65

STORAGE Fe Phagocytes & 1 – 1.5 25 -30

(ferritin & Hepatic Gms
hemosiderin) Parenchymal
MYOGLOBIN Redcells
Muscle 0.2 Gms 4
Myohemoglo Fibres 150-
Tracebin
Heme Tissue Cells 200mg
< 0.1 1
Tissue Gms
enzymes NOMAD:2006: BP: HBANEM 28
 IRON BALANCE
 ADULT MEN:
 DIET : 5 – 10 mg/day
 LOSS:

 0.4 mg : Urine

 0.8 mg : Bile

 Traces : Mucosa of GI

tract. NOMAD:2006: BP: HBANEM 29

 IRON BALANCE: women
 HAVE MORE IRON LOSS:
 Monthly Menstrual Periods: 50 – 80
ml
 Child Bearing & Rearing : 15 Months:
900 mg (2mg/day) How?
 Fetal Iron Content : 400mg.
 Iron in Placenta/Uterus : 150mg.
 Blood loss in Parturition:170mg.
 Iron in Breast milk : 180mg.
 TOTAL : 900mg.
NOMAD:2006: BP: HBANEM 30
 IRON ABSORPTION
 SITE: Duodenum/Upper Jejunum via
brush border.
 Ferrous form better absorbed than
Ferric form
 Ascorbic Acid (Vit C) helps
absorption.
 Phosphates/Phytates reduce ionic
Iron absorption by forming insoluble
salts.
 Heme in diet is directly absorbed
 Iron deficiency states enhance Iron
absorption. NOMAD:2006: BP: HBANEM 31
ANEMIAS
Deficiency of Hb in the
blood caused by either:
RBC Count or
Hb in the RBCs

NOMAD:2006: BP: HBANEM 32

NOMAD:2006: BP: HBANEM 33
ANEMIAS: CLASSIFICATION
 HEMORRHAGIC ANEMIA
 APLASTIC ANEMIA
 MEGALOBLASTIC ANEMIA
 PERNICIOUS ANEMIA
 HEMOLYTIC ANEMIA
 SICKLE CELL ANEMIA
 IRON DEFICIENCY ANEMIA
 SECONDARY ANEMIA (RENAL)
NOMAD:2006: BP: HBANEM 34
1. HEMORRHAGIC ANEMIA
(BLOOD LOSS)
 ACUTE: Sudden loss of blood
 RBC Count decreased for 1 – 3

days
 RBCs are restored in 3 – 6

weeks
 CHRONIC BLOOD LOSS:

 They cannot absorb Fe enough

to form Hb
 Have Hypochromic, Microcytic
NOMAD:2006: BP: HBANEM 35
2. APLASTIC ANEMIA:
 Lack of functioning Red Bone
Marrow, the hemopoietic tissue.
 Caused by exposure to gamma
ray radiation (Nuclear Bomb
Blast)
 Excessive exposure to X rays
 Exposure to certain industrial
chemicals.
NOMAD:2006: BP: HBANEM 36
3. MEGALOBLASTIC ANEMIA:
 Deficiency of Vit B12 and or Folic
Acid.
 Intrinsic Factor can also be
deficient.
 Production of Erythrocytes
becomes slow.
 They remain large, hve odd
shapes and are called
‘Megaloblasts’
 Atropy of Stomach mucosa can
NOMAD:2006: BP: HBANEM 37
 MEGALOBLASTIC ANEMIA:

 Intestinal Sprue or Malabsorption

Syndrome can also cause this.
 Megaloblasts are over sized,
anisocytic.
 They have fragile membranes and
rupture easily.
 TREATMENT: Vitamin B12 Folic Acid if
it is nutritional.

NOMAD:2006: BP: HBANEM 38

NOMAD:2006: BP: HBANEM 39
 4. HEMOLYTIC ANEMIAS
 Mostly heriditary.
 Cells are fragile, rupture easily as
they move through the capillaries.
 The life span of erythrocytes is
reduced.
HERIDITARY SPHEROCYTOSIS:
 Small spherical erythrocytes.
 Cannot be compressed even
slightly
NOMAD:2006: BP: HBANEM 40
 Rupture and are lysed very easily.
 5. SICKLE CELL ANEMIA
 Affects 0.3 to 1% of West African &
African blacks.
 The Beta chains of Hemoglobin are
defective.
 They have Hb S
 Sickling occurs when Hb loses
Oxygen.
 A vicious circle of events occurs:
Oxygen tension Sickling Rupture
of Erythrocytes
Further Oxygen tension
 This is called a crisis in sickle cell
disease. NOMAD:2006: BP: HBANEM 41
NOMAD:2006: BP: HBANEM 42
 ERYTHROBLASTOSIS FETALIS
 Rh Isoimmunisation causes this
disease
 Antigen antibody reaction
causes lysis of erythrocytes.
 Seen in Neonates and is also
called Icterus Gravis
Neonatorum.
 Excess Bilirubin enters the brain,
causing ‘kernicterus’
 Can become fatal.
NOMAD:2006: BP: HBANEM 43
 IRON DEFICIENCY ANEMIA
 The most common type of anemia.
 Caused by nutritional deficiency of
Iron.
 Erythrocytes are smaller and have
less Hb.
 So they are called Microcytic &
Hypochromic.
 Treated by taking Iron rich diets.
 Dark green leafy vegetables: esp
Drumstick leaves.
NOMAD:2006: BP: HBANEM 44
 Meats like Liver & spleen.
IRON RICH DIETS

NOMAD:2006: BP: HBANEM 45

 SECONDARY ANEMIA(RENAL)

 Renal Diseases can cause

decreased Erythropoietin.
 Erythropoietin is essential for
proper production of
erythrocytes (Erythropoiesis)
 Renal disease thus causes
Anemia.

NOMAD:2006: BP: HBANEM 46

 ANEMIA: EFFECTS ON CVS
 Decreased Blood Viscosity
 Decreased Peripheral
Resistance.
 Increased blood flow to tissues
 Increased Venous Return.

NOMAD:2006: BP: HBANEM 47

 ANEMIA: EFFECTS ON CVS
 So increased Cardiac Output.
 Hypoxia causes peripheral
vasodilatation which further
increases blood flow
 Higher work load on the heart
 Cardiac Reserve decreases.

NOMAD:2006: BP: HBANEM 48

 REVIEW
 Hemoglobin is a chromoprotein
present exclusively within the
erythrocytes.
 Hb synthesis takes place within the
normoblasts.
 Hemoglobin = Heme + Globin.
 Heme is an Iron containing Porphyrin.
 Iron is present in the Ferrous form.
 Oxygen can be loosely attached to
Hb.
NOMAD:2006: BP: HBANEM
NOMAD:2006: BP: HBANEM 49
49
 REVIEW
 Normal blood levels of
Hemoglobin:
 Males : 14 – 18 Gm%
 Females : 12 – 15 Gm%
 1 Gram of Hemoglobin combines
with 1.34 ml of Oxygen.
 Varieties of Hemoglobin include:
Hb A, Hb F
Hb S, Hb A2NOMAD:2006: BP: HBANEM 50
 REVIEW
 Anemia is a decrease in either Hb or
RBCs.
 Types of Anemia:
 Hemorrhagic

 Aplastic

 Megaloblastic

 Pernicious

 Hemolytic

 Sickle Cell

 Iron deficiency

 Secondary (Renal)
NOMAD:2006: BP: HBANEM
NOMAD:2006: BP: HBANEM 51
NOMAD:2006: BP: HBANEM 52