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What is the definition of anaemia?

Reduction in circulating red blood cell(RBC) mass. Hb in males < 13.5 g/dl
Hb in female <12.5 g/dl
(Normal Hb in males is 13.5 -17.5 g/dl and in females it is 12.5 -16 g/dl)


What are the signs and symptoms of Anaemia?

Anaemia presents with signs and symptoms of hypoxia:
Weakness, fatigue and dyspnea (shortness of breath)
Pale conjunctiva and skin (Good clinical test for anaemia)
Headache and lightheadedness (due to hypoxia of CNS)
Angina, especially with preexisting coronary artery disease


How do we measure RBC mass?

Measuring RBC mass directly is very difficult and expansive. Therefore we use surrogates marker to measure it indirectly.
The surrogates marker used to measure RBC mass include Hb, hematocrit (Hct) and RBC count.

All surrogate markers are concentrated dependent. So their value is also influenced by certain circumstances.


Classification of anaemia?

Anaemia can be classified based on Mean Corpuscular Volume (MCV).
Normal value of MCV = 80-100 µm³
microcytic anaemia (MCV < 80 µm³)
Normocytic anaemia (MCV=80-100 µm³)
Microcytic anaemia (MCV > 100 µm³)


Definition of microcytic anaemia?

It is anaemia with MCV<80 µm³


Microcytic anaemia is due to what?

Microcytic anaemia is due to decreased production of Hb. Normally the progenitor cell, erythroblast, in bone marrow are large and divide multiple time to form mature RBC. In each division the erythroblast becomes smaller. In microcytic anaemia the progenitor cell goes through an extra division than normal leading to formation of smaller mature RBC.
The reason it goes through an extra division is due to decreased Hb concentration in the cell, and In order to maintain the Hb concentration the erythroblast goes through one extra division .


What is Haemoglobin(Hb)?

Hb is made of heme and globin molecule.
Heme is composed of Iron and protoporphyrin.
Deficient of any of these components can lead to Microcytic anaemia


What are the four major causes of microcytic anaemia?

The four major causes of Microcytic anaemia include (1) Iron deficiency anaemia (There is a lack of Iron --> low heme --> low Hb --> microcytic anaemia)
(2) Anaemia of chronic disease (In chronic disease the iron is stored in macrophages and therefore is not available for usage, leading to decreased iron --> decreased heme --> decreased HB--> microcytic anaemia.
(3) Sideroblastic anaemia (decreased production of protoporphyrine leading decreased heme --> decreased Hb--> Microcytic anaemia.
(4) Thalassemia (Decreased production of Globin molecule leading to decreased heme --> Decreased Hb --> Microcytic anaemia


What is Iron deficiency Anaemia?

Iron deficiency anaemia is a type of microcytic anaemia caused by decreased level of Iron:
Decreased iron-->decreased heme--> decreased Hb --> microcytic anaemia


What is the most common type of anaemia?

Iron deficiency anaemia. Iron deficiency is the most common nutritional deficiency affect more than 1/3 of world's population.


What are the two form of dietary Iron?

Heme Iron and Non-heme Iron. Heme Iron is meat-derived and non-heme iron is vegetable derived. Heme Iron is more readily absorbed in duodenum.


What is the mechanism of Iron transportation?

Mechanism: Iron is absorbed in the duodenum. 1) Enterocyte absorb iron via DMT1 (Divalent Metal Transporter 1) transporter in Duodenum. 2) Enterocyte transport Iron across cell membrane into the blood via ferroportin. 3) In the blood Iron is bond to transferrin, and transferrin transport Iron to the liver and bone marrow macrophages. 4) Intracellularly Iron is stored by binding to ferritin. And binding of iron to ferritin prevent formation of free radical via Fenton Reaction.


What lab measurement do we use to determine the Iron statues in the body?

- Serum Iron: Measure of iron in the blood
- Total Iron binding capacity (TIBC): Measure of transferrin molecules in the blood.
- % Saturation: Percentage of transferrin molecules that are bond by Iron (Normally it is 33 %)
- Serum Ferritin: Reflect Iron stores in macrophages and liver


What are the most common causes of Iron deficiency in the blood?

Dietary lack or blood loss:
-Infants: Iron deficient due to breast feeding (Breast milk contains little to no Iron
-Children: Poor diet
-Adults aged 20-50: Peptic ulcer disease in Males and menorrhagia or pregnancy in female
-Elderly: Colon polyps/carcinoma in Western World, hookworm (Ancylostoma duodenale and Nector Americanus) in developing world.
-other causes: Malnutrition, malabsorption, Gastrectomy (Acid aids in maintaining the Ferrous form and the ferrous form is more readily absorbed than ferric form)


What are the stages of Iron deficiency?

- Storage of iron is depleted: decreased ferritin and increased TIBC
-Serum Iron is depleted: Decreased serum iron and decreased % saturation
- Normocytic anemia (very initial stages of Iron deficiency) : Bone marrow makes normal-sized, but few RBCs
-Microcytic, hypo chromic anaemia: Due sever deficiency of iron, bone marrow makes smaller rand fewer RBCs


What are the clinical features of Iron deficiency Anaemia?

- Anemia
- Koilonychia: Spoon shaped nails
- Pica: Persisten eating of non-nutritional substances such as Dirt or paint


What are the laboratory finding and treatment of Iron deficiency anaemia?

Laboratory Finding:
- Microcytic (MCV < 80 µm³), hypochromic anemia with increased RDW (Red blood cell Distribution Width).
- Decreased ferritin and increased TIBC
- Decreased serum Iron and decreased % saturation
- Increased FEP (Free Erythrocyte Protoporphyrin)

- Iron supplement (ferrous sulphate


What is Plummer-Vinson Syndrome?

It is Iron deficiency anaemia with oesophageal web and atrophic glossitis. It presents with anaemia, dysphagia and Beef-red tongue.


What is anaemia of chronic disease?

It is anaemia associated with chronic inflammation or cancer.
- Most of common type of anaemia in hospitalised patients.


Explain function of hepcidin, acute phase reactant, produced in Chronic disease.

- Hepcidin sequesters iron in storage site and thus limiting Iron transfer from macrophages to erythroid precursors--> reduced production of heme-->decreased Hb-->Microcytic anaemia
- Hepcidin suppresses the Erythropoietin(EPO) production--> decreased RBC production.


What are the laboratory finding for anaemia of chronic disease?

- Increased ferritin and decreased TIBC
- Decreased serum iron (bone marrow is not able to utilise the iron in macrophage and therefore it uses serum Iron) and decreased % saturation
- Increased FEP (free erythrocyte protoporphyrin) because Iron level of the body is affected while protoporphyrin synthesis is normal.


Treatment of anaemia of chronic disease?

- address the underlying cause and give exogenous EPO to the patient. EPO is useful to a certain subset of patient, especially cancer patient.


What is sideroblastic anaemia?

Anaemia caused by defective protoporphyrin synthesis: Decreased protoporphyrin-->decreased heme -->decreased Hb-->Microcytic anaemia


important reaction of Protoporphyrin synthesis?

Simplified reaction of protoporphyrin synthesis:
- Succinyl CoA ---- (ALA synthetase and B6 is cofactor)---> Aminolevulonic acid (ALA) ----(ALA dehydrogenase)---> porphobilinogen -->--->--> Protoporphyrin.

- Ferrochelatase attache protoporphyrin to Iron to make Heme (final reaction and occurs in mitochondria)


Consequence of protoporphyrin deficiency?

- Normally protoporphyrin is produced in the mitochondria of the erythroid precursor cells, and Iron is transferred from bone marrow macrophages to mitochondria of erythroid precursor cells, where it combines with protopophyrin to form heme.
- In protoporphyrin deficiency iron accumulates in the mitochondria of erythroid precursor cells forming ring of iron-loaded mitochondria around the nucleus of the erythroid precursor cells. These cells are also called ringed siderblasts hence the term sideroblastic anaemia.


Types of Sideroblastic anaemia?

congenital and acquired.
- Congenital caused by defect in ALAS (rate limiting enzyme)
-Acquired caused by:
- Alcoholism: damages the mitochondria and affects the protoporphyrin synthesis.
- Lead poisoning: inhibits ALAD and ferrochelatase
- Vitamine B6 deficiency: cofactor of ALAS. It is commonly seen in isoniazid treatment of tuberculosis.