ANEMIA

It is a clinical condition characterized by

• decreased RBC ( <4million/cu mm) or

• decreased Hb ( <12gm/dl )

• or both

• leading to decreased O2 carrying capacity.

 Grades of Anemia (Hb)

Mild – Hb 8-12 gm%

Moderate - Hb 5-8 gm%

Severe - Hb <5 gm%

 Classification
• Etiological or Whitby’s
classification (based on cause of anemia)

• Morphological or Wintrobes
classification
• ( based on size of RBC & Hb concentration)
 Etiological or Whitby’s classification
Based on cause of anemia
1. Haemorrhagic - due to blood loss.
Acute or Chronic

2. Dietary deficiencies

3. Abnormal Haemopoiesis/ Dyshaemopoiesis

4. Haemolytic
 1.Haemorrhagic Anemia

• Acute – sudden loss of blood

• Chronic – slow loss of blood due to

piles, worm infestation, peptic ulcer,
menorrhagia.
 1.Haemorrhagic Anemia
In acute blood loss body replaces.

• fluid portion of plasma in 1-3 days ,

• RBC concentration returns to normal within 3-6

weeks if no secondary haemorrhage.

• In acute blood loss morphologically anemia will

be Normocytic, Normochromic (acute loss)
 1. Haemorrhagic Anemia
• Chronic blood loss : slow loss of blood

• In chronic blood loss person cannot absorb enough

Fe from intestine to form Hb as rapidly as it is lost,
so Hb is decreased or less in amount.

• Morphologically In chronic blood loss anemia will

be Normocytic, Hypochromic anemia.
 2. Dietary deficiencies
• Due to Fe, vitamins, proteins etc.

 E.g. deficiency of
1. Vitamin B12,

2. Folic Acid ,

3. Intrinsic Factor
which leads to Megaloblastic Anemia.
 2. Dietary deficiencies

 Vitamin B12 deficiency due to

1. Atrophy of gastric mucosa,

2. Total gastrectomy,

3. Intestinal sprue.
 3. Abnormal Haemopoiesis/
Dyshaemopoiesis
• It results in Aplastic Anemia .
• (Aplastic - lack of functioning bone marrow )

• Causes – X-ray irradiation, cytotoxic drugs,

sulpha drugs, industrial chemicals.

• Dyshaemopoiesis characterized by decrease in all

types of blood cells
i.e. RBC’s, WBC’s, Platelets.
• Normocytic, Normochromic
 4.Haemolytic Anemia

• Due to excessive destruction of RBC’s.

• It can be
1. Intrinsic Haemolytic Anemia.

2. Extrinsic Haemolytic Anemia.

 4.Haemolytic Anemia
• Intracorpuscular defect (intrinsic)
a) Congenital / Hereditary Spherocytosis

b) Haemoglobinopathies - Sickle cell anemia,

Thalassemia

c) Erythroblastosis Foetalis

d) Glucose - 6 – PO4 dehydrogenase (G-6PD)

deficiency
 Glucose - 6 – PO4 dehydrogenase def.
• Genetic disorder that occurs most often in males .

• Defect in enzyme causes RBC to break down

prematurely. (hemolysis)

• It is often triggered by bacterial or viral infections

or by certain drugs
 4. Haemolytic Anemia
Extracorpuscular defects (extrinsic) acquired in
nature.
a) Antigen – Antibody reaction

b) Infection – malaria

c) Drugs / Poisons - quinine, aspirin, burns, snake

venom etc.

d) Hypersplenism – over activity of normal

destructive mechanism (cirrhosis, malaria, CML)
Morphological or Wintrobes classification
Based on size of RBC’s & its Hb conc.
Normocytic Normochromic Hypochromic
1. After acute All chronic
haemorrhage haemorrhages
2. All haemolytic
anemias except
thalassemia
3. Aplastic anemia
Macrocytic All Megaloblastic Secondary to liver
Anemias disease
(Vit.B12, FA or IF
deficiency)
Microcytic Chronic infections 1.Fe deficiency anemia
2. Thalassemias
 General clinical features of anemia

1. Generalized muscle weakness, tiredness.

2. Pallor of skin & mucus membrane.

3. Respiratory symptoms – breathlessness

(Dyspnoea), rate & force of respiration increased.
 General clinical features of anemia

4. CVS symptoms - palpitation, tacchycardia,

haemic murmurs.

5. CNS symptoms -
Cerebral hypoxia - lethargy, headache,
restlessness, confusion
tinnitus (ringing in ears)
 General clinical features of anemia
6. GIT symptoms - nausea, anorexia, constipation

7. Reproductive system - menstrual disturbances,

amennorrhoea, menorrhagia.

8. BMR (basal metabolic rate) - increased in severe

anemia.

9. Ocular manifestations - visual disturbances,

retinal haemorrhages, cotton wool spot
Koilonychia
 Self evaluation
• Etiological classification based on – -------
• Morphological classification based on ------

• All haemolytic anemias are ------- except -----

• All megaloblastic anemias are ----

• Microcytic hypochromic ----- e.g.

• General symptoms in anemia -----
 Pernicious/Addison’s Anemia
• Pernicious means destructive or injurious .

• It is a type of Megaloblastic Anemia due to

vitamin B12 deficiency as a result of failure of
Intrinsic Factor secretion by stomach.

• Usually it is due to auto immune atrophy of gastric

mucosa. Thus it is an Auto-immune disease.
 Pernicious/Addison’s Anemia
• Other causes may be total gastrectomy,
tropical sprue, Chron’s disease

• In 50% patients, Antibodies to Intrinsic Factor

seen.

• Occurs mainly between 45-65 yrs.

• Females affected more frequently than males.

 Pernicious/Addison’s Anemia
• Characteristic features:
1. Bone Marrow changes

2. Blood changes

3. Changes in GIT

4. Changes in Nervous System

 Pernicious/Addison’s Anemia
• Characteristic features:
1. Bone Marrow –
Anemia

Hypoxia

Increased Erythropoiesis

Hyperplastic Bone Marrow

 Pernicious/Addison’s Anemia

 70% proerythroblast & early NB. (Normally 30%)

 30% intermediate & late NB. (Normally-70%)

 This overactivity of Bone marrow is k/a

Megaloblastic hyperplasia of Bone marrow .
 2. Blood changes

• RBC’s –
Its counts decreases markedly <1 million/cu mm .

• Hb decreases < 12 gm%

• Diameter increases to 8.2µm (N – 7.2µm)

Anemia : Macrocytic, Normochromic

 2. Blood changes
• MCV increases 95-160 µm3 (fL) (78 - 94 µm3)

• MCH increases to 50 pg (28 - 32pg)

• MCHC normal because both MCV & MCH

increases. (33% - 38%)
 Pernicious/Addison’s Anemia

• Peripheral smear - shows nucleated RBC’s,

marked anisocytosis & poikilocytosis.

• Reticulocyte count increases >5%. (N - <1%).

• WBC’s & Platelets decreases

(encroachment of Megaloblastic Tissue).

• Excessive destruction of RBC’s in spleen, liver,

Bone marrow. Decreased life span of RBC’s .
 Pernicious/Addison’s Anemia

• Serum bilirubin increases > 1mg%

(0.2-0.8mg%)

• Urine UBG (Urobilinogen)excretion increases.

• Serum Fe & Ferritin increases because Fe is not

utilized by immature RBC’s .
(N-60-160µgm%)
 Pernicious/Addison’s Anemia

• Vitamin B12 excretion increases to 90% in faeces

due to poor absorption.

• Serum Vit. B12 levels decreased.

 3. Changes in GIT in Pernicious Anemia
• Atrophic gastritis
(atrophy of gastric
mucosa)

• Deficiency of Intrinsic
Factor

• Soreness &
inflammation of tongue

• Loss of appetite
Soreness &
(anorexia) & Diarrhoea
inflammation of tongue
 4. Changes in Nervous System
• Sub acute combined degeneration of spinal cord
(in advanced cases demyelination of white fibres
of S. cord affecting dorsal column & later lateral
column)

• Tingling & numbness in hands & feet.

• Motor & psychological disturbances.

• Apathy (mental sluggishness).

 Signs of improvement
• Treatment- administration of Vitamin B12 by
intramuscular route.

• Increase in no. of circulating Reticulocyte (30-40%)

• Normoblastic reaction of Bone marrow within

6-9 hrs of treatment.

• Excessive destruction of RBC’s decreased

(Serum bilirubin returns to normal)
• WBC’s & Platelet count increases.
 Signs of improvement
• Cell metabolism increases, patient feels stronger.

• Loss of appetite, digestive disturbances,

apathy disappear.

(Prevents further progression of Central

Nervous System lesion but cannot reverse
damage already done)
 Megaloblastic Anemia
• Folic acid deficiency leads to megaloblastic
anemia.

• Features same as with vitamin B12 deficiency

except that
• neuropathy does not occur, in Folic Acid
deficiency.

• Sources of FA
• green vegetables, some fruits, liver & meat.
 Causes of Folic Acid deficiency
• Decreased intake

• Decreased absorption - tropical sprue, Crohn’s

disease.

• Increased demand - pregnancy, lactation,

infancy, haemolysis, malignancy

• Drugs – anticancer drugs, anticonvulsants,

contraceptive pills
 Iron deficiency anemia
• Commonest in India.

• Any anemia which responds to adequate dose of

Fe is Iron deficiency anemia.
 Causes (Fe deficiency anemia)
1. Decreased intake (milk fed infants)

2. Decreased absorption - due to disease of

stomach & duodenum.

3. Increased demand - infancy, childhood,

pregnancy, menstruation.

4. Increased loss- acute or chronic

haemorrhage
 Iron deficiency anemia
Characteristic features
1. RBC’s - are Microcytic, Hypochromic
• RBC count decreased or normal

• MCV, MCH, MCHC, CI values decreased

• Osmotic fragility decreased

• Life span normal

• PBS - Anisocytosis , Poikilocytosis
 Characteristic features of Fe deficiency
2. Bone marrow – Normoblastic hyperplasia

3. WBC’s & Platelet counts are normal

4. Investigation –
S.bilirubin normal
Serum Fe decreases
Total Iron Binding Capacity increases
Iron deficiency anemia
 Characteristic features of Fe def.
5. Nails – soft, dry, spoon shaped

6. Tongue - angry red

7. CVS & Respiratory system – breathlessness,

palpitation, repeated chest infection

8. Nervous system - irritability, loss of

concentration, headache, general body ache
Treatment – oral administration of iron salts.
Koilonychia
 Hereditary Spherocytosis

• Inheritance autosomal dominant

• Cause -
below the cell membrane contractile layer of
lipoprotein Spectrin is defective due to genetic
glycolysis defect.
 Hereditary Spherocytosis
• Features –
1. RBC’s are very small & spherical, biconcavity lost.

2. Osmotic Fragility increased, life span decreased to

15-20 days.

3. Spleenomegaly

4. S. bilirubin increased producing haemolytic

jaundice.
 Sickle cell anemia

• Inheritance as autosomal recessive.

• Seen in West African & American Blacks.

• Cells contain abnormal HbS due to abnormal β

chains of Hb molecule.
 Sickle cell anemia

• In each β chain of HbA at position 6 one

glutamic acid is replaced by a valine.

• This HbS when reduced due to low O2 tension

or low PH in tissues

• it precipitates into crystals within RBC’s being less

soluble.
 Sickle cell anemia
• Sickle shaped RBC’s with increased Osmotic
Fragility.

• Blood viscosity increased leading to decreased

blood flow to tissues.

• Hypoxia causes severe anemia due to precipitation

of HbS.

• Patient dies due to severe anemia & secondary

infections.
 Haemolytic disease of Newborn

• It occurs as a result of Rh incompatibility between

mother (Rh-ve) & fetus (Rh+ve).

• Sensitization of Rh-ve mother by carrying Rh+ve fetus

generally occurs at birth

• It occurs by small amount of fetal leaks into maternal

circulation.

• ABO incompatibility rarely produce Haemolytic disease of

newborn (α & β ABs are IgM type) .
 Haemolytic disease of Newborn
• Mother responds by forming Rh Antibodies which
returns to fetal circulation & tends to destroy fetal
RBC’s.

• First child is usually normal, serious results may

occur in 2nd or later pregnancies depending on
degree of sensitivity of mother

• (exception Rh+ve transfusion at any time, even in

childhood, dangerous response in 1st pregnancy
may occur).
 Haemolytic disease of Newborn
• K/a as Haemolytic disease because changes in
fetus are due to destruction of RBC’s by maternal
anti D.

• Manifestations – depending upon severity

1. Hydrops Fetalis

2. Icterus Gravis Neonatarum

3. Kernicterus
 Hydrops Fetalis
• Fetus grossly oedematous.

• Haemolysis very severe.

• Usually Intra Uterine death of fetus,

• If born prematurely or even at term, infant

dies with in few hrs.
 2. Icterus gravis neonatorum
• Infant born at term is jaundiced or becomes so
in 24 hrs

• Due to excessive destruction of RBC’s

(excessive bilirubin, haemolytic jaundice).
• Anemia develops in few days, after birth.

• Anti Rh agglutinins circulate in infants blood for

1-2 mths after birth,

• destroying more & more RBC’s.

 2. Icterus gravis neonatorum

• Haemopoietic tissue of infant attempt to replace

haemolysed RBC’s.

• Liver & spleen becomes greatly enlarged.

• Because of rapid production of cells many early

forms of RBC’s, including nucleated blastic
forms are passed from B. marrow to circulation.
 2. Icterus gravis neonatorum
• Because of presence of these nucleated blastic
RBC’s the disease k/a Erythroblastosis Fetalis

• Reticulocyte count is high.

• Severe anemia is usually the cause of death.

 Haemolytic disease of Newborn
3. KERNICTERUS
• It is a neurological syndrome occuring in newborns with
severe haemolysis.

• Excessive bilirubin formed may enter the brain tissue as

Blood Brain Barrier is not well developed in infants.

• Cause damage to motor areas of brain (Basal Ganglia)

due to ppt. of bilirubin in neuronal cells, causing
destruction & a condition k/a Kernicterus.

• (serum bilirubin when exceeds 18 mg %)

 Erythroblastosis Fetalis
• Prevention – single dose of Rh Ig (immunoglobulin)
soon after child birth which prevents active
antibodies formation by the mother i.e. prevents
sensitization of mother.

• Treatment –
• Exchange blood transfusion soon after birth
(compatible Rh –ve blood)
 Exchange transfusion

• This procedure may be repeated several times

during first few weeks of life to keep bilirubin low
and thereby prevent Kernicterus.

• Six or more weeks are required, and the anti Rh

Antibodies will have been destroyed that have
come from mother during this time period.
 Erythroblastosis Fetalis

• Haemolytic disease of new born.

• Cause –
• Destruction of fetal RBC’s by Maternal Antibodies
when fetus is Rh+ve
And mother is Rh-ve .
 Effects Of Anemia On Circulatory System
• Anemia

• Decreased viscosity

• Decreased peripheral resistance

• Increased Cardiac Output

• In severe anemia Cardic Output may increase 3-4 times.

• So major effects of anemia is greatly increased pumping
workload on heart.