Mechanism of Anaemia

Question 1

What is anaemia?

Answer 1

Low number of RBC or Hb in the blood. This reduces O2 delivery and causes weakness, shortness of breath and confusion.

Question 2

What are the signs of anaemia?

Answer 2

Tachycardia- HR increases to compensate for reduced O2 delivery
Conjuctival pallor (pale undereyes)- Limited O2 containing blood is directed to the vital organs

Question 3

What is the indication of dark urine/haemoglobinurea?

Answer 3

Haemolytic anaemia where excessive bilirubin is excreted due to too much RBC breakdown.

Question 4

What is the indication of koilonychia (spoon nails)?

Answer 4

This is thin and brittle spoon shaped nails caused by hypochromic microcytic anaemia, where there is iron deficiency.

Question 5

What is the indication of glossitis?

Answer 5

This is a swollen and painful tongue caused by a B12 deficiency

Question 6

What are the severe implications of anaemia?

Answer 6

Jaundice: Caused by haemolytic anaemia, resulting in build-up of bilirubin which enters the liver and cause hepatic jaundice
Splenomegaly progressing to hepatomegaly: Spleen is the site of RBC breakdown by macrophages. When the spleen is overworked, it enlarges due to macrocytic anaemia where the RBC is too large or haemolytic anaemia where there is excessive breakdown. This causes build up of bilirubin entering the liver
Angina/cardiac failure- due to tacycardia

Question 7

What is an erythroid?

Answer 7

Immature RBC which is regulated by EPO and macrophage interactions in the bone marrow to form a RBC.

Question 8

What is the haematopoietic growth factor?

Answer 8

Erythropoietin/EPO. It is inversely proportional to O2 levels -> When O2 is low, EPO production increases.

Question 9

What is the site of EPO production?

Answer 9

Synthesised by Juxtatubular/juxtaglomelular cells in the renal cortex of the kidney. They respond to O2 levels via the oxygen-dependent enzyme prolyl hydroxylase which regulates hypoxia inducing factor-alpha. In low O2, this enzyme is inhibited which enables stabilisation of HIF to stimulate EPO production by the juxtaglomeulular cells.

Question 10

What affects EPO production?

Answer 10

Greater EPO production in low O2 environment with greater levels of HIF-alpha

Question 11

What is pure red cell aplasia?

Answer 11

Disease which affects only erythropoiesis. If it is acquired later in life, primary cause is idiopathic. Secondary cause is infection or drug.

Question 12

What is a common congenital pure red cell aplasia?

Answer 12

Congenital Diamond Black fan anaemia when there is low proliferation of erythroblasts into mature erythrocytes.

Question 13

What is pancytopenia?

Answer 13

Disease which reduces production of RBC, WBC and platelets. Damage to the Haemopoietic stem cell caused by drugs, genetics or infections reduces self renewal. This exhausts the HSC and leads to reduced differentiation into RBC/WBC/platelet

Question 13

What is haemolytic anaemia?

Answer 13

Premature destruction of RBC less than 120 days old in the spleen greater than the production of new RBC in the bone marrow. Caused by extrinsic drugs or intrinsically as a result of autoimmune disease

Question 14

What is an autoimmune haemolytic anaemia?

Answer 14

Auto-antibodies destroy self-RBCs. Majorly idiopathic. May be caused by
lymphoproliferative disease that means the lymphocytes produced attack the RBCs. Extrinsic causes include medicines like penicillin which bind to RBC and result in complement activation of antibodies to destroy both the drug and the RBC.

Question 15

Examples of lymphoproliferative disease?

Answer 15

Chronic lymphocytic leukaemia and lymphoma.

Question 16

What are spherocytes?

Answer 16

Small and spherical RBCs, indication of autoimmune haemolytic anaemia.

Question 17

What are schistocytes?

Answer 17

Fragments of erythrocytes, indication of haemolytic anaemia caused by trauma-related anaemia.

Question 18

What is polychromasia?

Answer 18

Blue tinged reticulocytes present in circulation. Indication of anaemia because of premature release of RBC to supplement low levels.

Question 19

What is haemoglobinopathy?

Answer 19

Disorder where there is mutation of globin chains of haemoglobin which disrupts transport of O2

Question 19

What is haemoglobinopathy?

Answer 19

Disorder where there is mutation of globin chains of haemoglobin which disrupts transport of O2

Question 20

What is sickle cell anaemia?

Answer 20

A type of haemoglobinopathy which affects beta-globin chain and causes sickle shape of erythrocytes which affects o2 delivery.

Question 21

What are the essential micronutrients in diet for erythrocyte production?

Answer 21

Vitamin B6, B12, folate and iron regulate production of haem in the cytoplasm. B12 and folate are essential for DNA synthesis of healthy erythrocytes during erythropoiesis.

Question 22

Why does macrocytic anaemia occur?

Answer 22

Large RBC which may be nucleated due to B12 or folate deficiency which regulates erythrocyte DNA synthesis.

Question 23

What are sources of B6?

Answer 23

Meat, salmon, eggs, milk and soy.

Question 24

What is iron deficiency anaemia?

Answer 24

Lack of iron that reduces RBC production; iron is an important cofactor in haem. Caused by malnutrition or malabsorption. It leads to hypochromic microcytic anaemia where the RBCs are small and pale.

Question 25

What are the daily iron requirements?

Answer 25

Highest for menstruating adolescent and pregnant women at 3-5mg. Lowest for infant, adult males and post menopausal females at 1mg.

Question 26

What disorders affects iron absorption?

Answer 26

Alcoholism. Disorders of the stomach such as achlorhydria where there is no HCL. Crohn’s disease which is inflammation of the gut.

Question 26

Where does iron absorption occur?

Answer 26

In the duodenum and proximal jejunum. Gastric acidity is essential for iron absorption.

Question 27

What are sources of iron?

Answer 27

Dark-green leafy veg, whole grain, meat, prunes, raisins and beans.

Question 27

What are sources of iron?

Answer 27

Dark-green leafy veg, whole grain, meat, prunes, raisins and beans.

Question 28

Which foods disrupt iron absorption?

Answer 28

Tea, coffee, antacids, calcium, wholegrain cereals.

Question 29

What is sideroblastic anaemia?

Answer 29

Congenital disorder where there is a failure to incorporate iron into haem and forms iron-rich granules in the mitochondria.

Question 30

What is thalassaemia?

Answer 30

Insufficient production of haemoglobin that reduces MCV and ferritin (iron) levels.

Question 31

What is ferritin?

Answer 31

Blood protein containing Iron

Question 32

What is the cause of microcytic anaemia?

Answer 32

Iron deficiency due to malnutrition or malabsorption caused by GI disease, lead poisoning, thalasemmia or sideroblastic anaemia.

Question 33

What is the cause of normocytic anaemia

Answer 33

Haemolytic anaemia caused by blood loss or autoimmune disease
Kidney disease due to drop in EPO
Hypersplenism due to removal of RBC by splenic macrophages

Question 34

What is the cause of macrocytic anaemia?

Answer 34

Folic acid/ B12 deficiency caused by malnutrition/malabsorption due to GI tract disease
Liver disease -> site of TPO and EPO production

Question 35

Where does TPO production occur?

Answer 35

In the liver.

Question 36

Where does EPO production occur?

Answer 36

Liver

Question 37

How does liver disease affect blood count?

Answer 37

Liver disease caused by alcohol consumption for example results in macrocytic anaemia because the liver is the site of EPO production. It causes thrombocytopenia because the liver is the site of TPO production.

Question 38

Why does yellow marrow revert to red marrow?

Answer 38

Due to fever (to produce more WBC) or blood loss (to produce more RBC)

Question 39

What are the two categories of haematopoietic stem cells?

Answer 39

Myeloid or lymphoid.

Question 40

When to avoid iron treatment?

Answer 40

During infection- excessive iron may aid pathogens .