Anaemia note

7/30/2019 Anaemia note

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ANAEMIA

Dr R. Z. Azma


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Anaemia

Defination:

Anaemia - haemoglobin (Hb)

- red blood cells (RBC)(reduction of more than 10% of the normal

value of Hb or total number of RBC for age

and sex)


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Reference ranges for Hbs at different ages

Age group Hb range (g/dl)

Newborn (< 1 week) 14 22

6 months old 11 14

Children (1 16 years) 11 15

Adults

Men

Women

13 16

12 - 14


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Anaemia

Clinical grading (Adults)

Mild (Hb > 10 g/dl) Asymptomatic

Moderate (Hb 7 10

g/dl)

Pallor, lethargy

Dyspnoea, vertigo

headache

Severe (Hb < 7 g/dl) Tachycardia

hypotension


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Mechanisms of anaemia

Production of RBCs depends on:

Haemopoietic stem cells (to function

satisfactorily)

Erythroid precursor cells (normal maturation and

released into circulation)

Hb synthesis (to function normally)


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Mechanisms of anaemia

1. Decreased production

Ineffective erythropoiesis

Deficiency of B12/folate

Abnormal synthesis of haemoglobin (thalassaemia) Decreased effective erythropoiesis

Aplastic anaemia/marrow failure

2. Increased blood loss

Gastrointestinal bleeding

3. Increased destruction

haemolysis


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Classification of anaemia

1. Morphological

Based on red cell indices and blood film

Hypochromic microcytic anaemia (MCV , MCH)

Normochromic normocytic anaemia (MCV N, MCH N) Normochromic macrocytic anaemia (MCV , MCH N)

2. Pathophysiological

Based on causes of anaemia

Iron deficiency anaemia Megaloblastic anaemia

Haemolytic anaemia


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Classification of anaemia

MCV mean corpuscular volume (fl)

MCH mean corpuscular Hb (pg)

MCV (80 100 fl) Normocytic

MCV (< 80 fl) Microcytic

MCV (>100 fl) Macrocytic

MCH (27 - 32 pg) Normochromic

MCH (< 27 pg) Hypochromic


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Physiological adaptations to anaemia

Reduced delivery of oxygen to tissues

Increased erythropoietin secretion by kidneys

More rapid delivery of blood

Heart rate and respiratory rate increased Cardiac output increased

Increased in RBC 2,3 DPG shifts oxygendissociation curve to the right.


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Iron deficiency anaemiaA form characterized by low orabsent iron store, low serum

iron conc, low transferrin

saturation, elevated transferrin,low Hb conc or hematocrit, nhypochromic, microcytic rbc


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Epidemiology

Iron deficiency anaemia (IDA) is the

commonest macronutrient deficiency in man

despite abundant iron content in the earth

crust.

30% of world population

50% of pregnant women 20% women

3% of men


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Aetiology

IDA - reduction in iron supply to red cellprecursors.

Causes1. Dietary - defective intake of iron: poverty, religious

tenets, vegetarian2. Increase physiological requirement infants, children,

pregnancy

3. Blood loss - GIT (peptic ulcer, haemorrhoids),menorrhagia.

4. Malabsorption partial gastrectomy, gluten inducedenteropathy


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Aetiology

IDA - reduction in iron supply to red cellprecursors.

Causes1. Dietary - defective intake of iron: poverty, religious

tenets, vegetarian2. Increase physiological requirement infants, children,

pregnancy

3. Blood loss - GIT (peptic ulcer, haemorrhoids),menorrhagia.

4. Malabsorption partial gastrectomy, gluten inducedenteropathy


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Clinical features

Symptoms Signs

Anaemia

Lethargy

Dyspnoea

Headache

Poor concentration

Palpitation

IDA deficiency

Dysphagia

Anaemia

Pallor

Tachycardia

IDA deficiency

Painless glossitis

Angular stomatitis

Koilonychia

Skin atrophy


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Clinical features

Koilonychia in severe iron

deficiency aneamia

Hiatus hernia can cause IDA


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Laboratory investigations

Full blood count FBC

Hb

MCV

MCH.

Peripheral blood film

Serum iron and TIBC Serum ferritin

Bone marrow iron (rarely)


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Laboratory investigations

Typical results seen in iron def. anaemia

Reduced Haemoglobin

Reduced MCV, MCH, MCHC

Peripheral blood film: hypochromic microcytic

anaemia

Reduced serum iron with raised TIBC

Reduced serum ferritin

Absent iron stores in bone marrow


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Full blood picture of iron deficiency anaemia


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Treatments

To correct anaemia and replenish iron

stores:

Oral iron

Parenteral iron

Treat the underlying causes.


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Megaloblastic Anaemia

Characterized by megaloblast

in bm, such s PA


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Megaloblastic anaemia

Causes

Vitamin B12 deficiency

Folate deficiency


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Impaired synthesis of DNA due to reducedsupply of the immediate precursors of DNA

dA(adenine)TP and dG(guanine)TP (purines)

dT(thymine)TP and dC(cytosine)TP (pyrimidines)

Folate def: impairs in synthesis of dTTP folate is coenzyme for thymidylate synthesis.

Vit B12 - cofactor to convert methyl THF

which enters the cell fr plasma to THF.


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slow demethylation

of methyl THF

THF

purine

synthesisLack of B12

supply of precursors

needed for DNAsynthesis

incomplete

replication of

chromosomal DNA

Ineffective

haemopoiesis

In severe def

affect all

3 cell lines

(pancytopenia)

apoptosis ofNRBC in BM


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Vit B12 def

CAUSES

Malabsorption Gastric causes

Pernicious anaemia

Congenital IF absence/abn fx

Total/partial gastrectomy

Intestinal causes Fish tapeworm

Intestinal stagnant loop syndrome

Ileal resection

Crohns ds

Inadequate dietary intake Vegetarian poverty


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Pernicious anaemia

MA,affect older adults due 2 failure of gastric

mucosa 2 secrete adequate n potent IF

Severe lack of IF gastric atrophy.

Autoimmune in origin

May a/w myxoedeme, Hashimotos ds, Addisonsds, vitiligo, hypoparathyroidism &hypogammaglobulinaemia.

Occur in families, F > M, 60 yr, blood gp A

incidence of Ca stomach. Thin stomach wall, plasma cell & lymphoid infiltrate

of the lamina propria


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Pernicious anaemia : (L) normal, (R) atrophy of all coats, loss of gastric

glands & parietal cells & infiltration of the lamina propria by lymphocytes &

plasma cells achlorhydria & sec. of IF is absent.


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Pernicious anaemia :

showing premature

greying, blue eyes &

vitiligo


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Marked vitiligo

P i i i


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Pernicious anaemia

Antibodies :

- 90% ; parietal cell Ab in serum

- 50% ; type I or blocking Ab to IF ( inhibit IF bind to

B12 )

- 35% ; type II or precipitating Ab to IF, inhibits itsileal binding site.

- 50% ; IF Ab, inhibit IF fx in gastric juice.

Congenital PA : presentation develop after age of 2

( Cong. Lack of IF )

F l t d f


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Folate def

CAUSES

Nutritionalvegetarian, poverty, goats milkanaemia

Malabsorption tropical sprue, Coeliac ds, partial

gastrectomy, Crohns ds Excess utilization pregnancy, haematological ds,inflammatory ds.

Excess urinary loss active liver ds, CHF

Drugs anticonvulsants, hyroxyurea Others alcoholism, intensive care.

C li di


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Coeliac disease

Coeliac disease (gluten-sensitive enteropathy orcoeliac sprue) is disease of small intestine.

Gluten (substance found in wheat, barley and rye)

activates the immune system and causing damageto the delicate lining of the small bowel -responsible for absorbing nutrients and vitamins.

Histological section of jejunal bx villous atrophywith absence of vili and hypertrophy of the mucosalcrypts


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Figure 1: Healthy villi of

the small intestine (as

seen under the

microscope).

Figure 2: Damaged villi

of the small intestine.Figure 3: Villi

completely destroyedby the immune system.

Absence of vili and

hypertrophy of the

mucosal crypts

Cli i l f t


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Clinical features

Symptoms and signs of

anaemia

Weakness

Tiredness

Shortness of breath

Pale

Angina

Heart failure

Symptoms and signs of

b12/folate deficiency

Glossitis

Angular cheilosis

Neurological symptoms

Cli i l f t


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Clinical features

Lemon-yellow

appearance

combination anaemia& jaundice ( excessive

Hb breakdown in BM

due to ineffective

erythropoiesis )


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Glossitis - the tongue is

beefy-red & painful

due to impaired DNA

synthesis in the mucosal

epithelium.

Angular cheilosis -

due to impaired

proliferation of

epithelial cells

Cli i l f t


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Clinical features

Neurological symptoms :- numbness

- spastic ataxia : demyelination of the lateral &

posterior columns

- Brain involvement : optic atrophy

somnolence

dementia

frank psychosis


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General tissue effects of cobalamin &

folate deficiency

Severe def. will affect rapidly growing ( DNA-synthesizing ) tissues :

Marrow : megaloblastic anaemia

Macrocytosis of epithelial cell surfaces ; mouth,stomach, small intestine,respiratory, urinary &

female genital tracts.

Prematurity maternal c folate def.

Neural tube defects folate def in early

pregnancy


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Cobalamine def may cause:

bilateral peripheral neuropathy / degeneration of the post.

& pyramidal tracts of the spinal cord

Rarely: optic atrophy and mental abnormalities Long term def in infancy leads to poor brain

development & impaired intellectual development.

Cause : accumulation of S adenosyl

homocysteine ( excessive homocysteine entry, no

B12 to convert to methionine )

VITAMIN B12 NEUROPATHY( Subacute combined degeneration of the cord )


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Pernicious anaemia : cross section of spinal cord of a pt who died c severe vit

B12 neuropathy ( subacute combined degeneration of the spinal cord ). There

is demyelination of the lateral & posterior columns

Laboratory findings


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Laboratory findings

FBC: Anaemia, in

severe def

pancytopenia, high

MCV, normal MCH.

PBF: Macrocytosis

with

anisopoikilocytosis


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PBF: Hypersegmented neutrophils


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BMA: Hypercellular - megaloblasts with dyserythropoiesis..


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giant metamyelocytes


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..hyperpolypoid megakaryocytes.

Other blood investigations


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Other blood investigations

Serum folate low in folate deficiency

Serum B12 low in B12 deficiency

Management

Folate deficiency Tablet folic acid daily

B12 deficiency Intramuscular hydroxocobalamin,

every 3 months.

Those with Subacute combined degeneration of thecord if treat with folate without B12, worsen the

condition.


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HAEMOLYTIC ANAEMIA

Any of heterogenous grp of inherited anemias characterized byshortened rbc survival, lack of spherocytosis, n normal osmotic

fragility with erythrocyte membrane defects, multipleintracellular enz def or other defect or unstable Hb

Haemolytic anaemia


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Haemolytic anaemia

Normal RBC lifespan is 120 days after whichthey are removed by RES (marrow, liver,

spleen).

Haemolytic anaemia anaemia due to

increased rate of red cell destruction.

Erythroid hyperplasia and anatomical

expansion of the marrow.

Haemolytic anaemia


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Haemolytic anaemia

The normal adult marrow is capable ofproducing red cells 6 - 8x more than normalrate, provided that there is adequate supplyof iron, folate and B12.

HA is seen when the red cell survival is lessthan 30 days.

Mechanism:

Intravascular: haemolysis occur in circulation Extravascular: removal of RBC in the RES


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Clinical features


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Pallor

Mild Jaundice

Splenomegaly

Some may have painful right abdomen

(chronic haemolysis pigment gallstone) Haematuria (intravascular haemolysis)

Bossing of frontal and parietal bones

mongoloid appearance (marrow expansion inchronic haemolysis)

Clinical features

Laboratory findings


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Anaemia with reticulocytosis.

PBF showed: spherocytes with

polychromatic cells (reticulocytes).

Laboratory findings

Spherocytes

Laboratory findings


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serum bilirubin

urine and faecal urobilinogen serum haptoglobin Bone marrow: erythroid hyperplasia

compensation mechanism

Ultrasound of abdomen gallstone

Laboratory findings

Laboratory findings


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Features of intravascular haemolysis

(others similar with extravascular haemolysis) Fragmented red cells (schizocytes) seen in

PBF.

Haemosiderinuria (iron storage protein,derived from the breakdown of Hb in therenal tubular cells)

Haemoglobinaemia

Haemoglobinuria

Laboratory findings

S


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Classification of HA


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Hereditary haemolytic anaemia

Acquired haemolytic anaemia



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HEREDITARY HAEMOLYTIC ANAEMIA

Membrane

defects

Metabolic

defects

Haemoglobin

defectsHereditary

Spherocytosis

G6PD def Defective synthesis

(thalassaemia /)H. Elliptocytosis / H.

Pyropoikilocytosis

Pyruvate kinase def Abnormal variants

(eg. Hb S, Hb C,

unstable)

H. Stomatocytosis Pyrimidine 5-

nucleotidase def

South-east Asian

ovalocytosis

Glutathione

synthase def


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ACQUIRED HAEMOLYTIC ANAEMIA

IMMUNE NON-IMMUNE

AUTOIMMUNE

Warm

autoimmune

HA

Cold

autoimmuneHA

Haemolytic

Transfusion

Reaction

INFECTIONS

FRAGMENTATION

SYND

CHEMICAL AND

PHYSICAL

AGENTS

DRUGS

ALLOIMMUNE

Haemolytic

Disease ofNewborn

G6PD deficiency


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G6PD deficiency

G6PD catalyses the first step of pentose

phosphate pathway to produce NADPH.

Def of G6PD NADPH production lack ofreduced glutathione (GSH) which protect themembrane Hb & other cell structure fr oxidant

damage.


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G6PD deficiency


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G6PD deficiency

Mild G6PD deficiency is usually asymptomatic.

It is present in all cells but patient become

symptomatic in response to oxidant stress

(drugs, fava beans) or infections. In severe G6PD patient may have chronic

haemolytic anaemia.

Clinical findings: anaemia, mild jaundice,haematuria

G6PD deficiency


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G6PD deficiency

Lab findings;

FBP: red cells with

contracted Hb in ghostmembrane blister cells,bite cells, NRBC

Haemoglobinuria

Haemosiderinuria Screening test:

Ultraviolet spot testnegative

G6PD assay(quantitative): low(The screening andquantitative tests should notbe done during acute event)

Thalassaemia


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Thalassaemia

Results from a reduced synthesis of or

chains. Autosomal recessive inheritance

Classifications:

Genetic If no globin chain is synthesized at all0 / 0-

thalassaemia

If some is still produced+ / +-thalassaemi

Clinical

Thalassaemia


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Thalassaemia

Clinical classifications classified according to

degree of severity of symptoms:1.Major = severe anaemia and transfusion dependent.

2. Intermedia = anaemia and splenomegaly

3.Minor = symptomless carrier only show changes in red

cell indices (hypochromic microcytic red cells).

Symptomatic for HA:

thal major,Hb Barts and HbH ds

Thalassaemia


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Thalassaemia

thalassaemia syndromes majority of geneticlesions are point mutations.

thalassaemia trait (o or+) - asymptomatic(clinically minor)

thalassaemia major (oo oro+)

symptomatic: Either no chain (o) or small amounts (+) are

synthesized.

Excess chains precipitate in erythroblasts and inmature red cells causing ineffective erythropoiesis andhaemolysis.

Thalassaemia


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Thalassaemia

Beta thal major inheritance

Thalassaemia


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Thalassaemia

Clinical features

(major):

Severe anaemia

Hepatosplenomegaly

excessive red cell

destruction and

extramedullary

haemopoiesis.

Expansion of bones

marrow

hyperplasia

thalassaemic facies.

Thalassaemia


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These are usually due to gene deletions

Asymptomatic in 1 or 2 gene deletions (/- ,

- /- or/--)

Symptomatic when 3 or 4 gene deletions (-/-- or --/--).

Hb H 3 gene deletions, small amount chain

available excess beta chain forming tetramers(4)and precipitate in red cells (known as Hinclusions).

Thalassaemia


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Patient survived till old age and some times require blood

transfusion (thalassaemia intermedia).

Hb H inher i tance

Thalassaemia


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Hb Barts, no available

globin chain: failure foetal Hb

synthesis (eg. Hb F). Excess chain forming

tetramers (4 known asHb Barts).

death in utero or at birth

Hydrop fetal is inher i tance


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Anaemia note