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Block 4 Lectures > Week 1: Outline the mechanisms of Anaemia > Flashcards

Week 1: Outline the mechanisms of Anaemia Flashcards

1
Q

What is anaemia?

A

Anaemia is caused by a reduced number of red blood cells in circulation, or a decreased amount of haemoglobin in the red blood cells

This results in reduced levels of oxygen delivery to tissues
Anaemia may be significant before a patient appears pale

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2
Q

What are signs of anaemia?

A

Pallor (especially of the conjunctiva)
Tachycardia (Pulse rate over 100 beats per minute)
Glossitis (swollen and painful tongue - reasonably specific for vitamin B12 deficiency)
Koilonychia (spoon nails - reasonably specific for iron deficiency)
Dark Urine ( in haemolytic anaemia)

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3
Q

What is the aetioological classification of anaemia?

A
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4
Q

Write down the process of erythropoesis

A
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5
Q

What takes place in the blood and the bone marrow in Erythropoiesis?

A

The final conversion from reticulocytes to erythrocytes

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6
Q

What is a sign of anaemia in regards to number of reticulocytes?

A

Higher number of reticulocytes means earlier release of immature RBCs to compensate for breakdown of red blood cells elsewhere

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7
Q

What is the precursor for all Blood cells?

A

Multipotential hematopoietic stem cell

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8
Q

What is the relationship between erythropoietin and tissue oxygenation?

A

They are inversely related

Erythropoietin can increase up to 1000X in response to anaemia

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9
Q

What controls the production of erythropoietin?

A

The juxtatubular interstitial cells of the renal cortex produce approximately 90 percent of the EPO in blood. They sense oxygen levels through oxygen-dependent prolyl hydroxylase that regulates the stability of the primary transcription factor for EPO, hypoxia-inducible factor 1(alpha) (HIF-1(alpha)).

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10
Q

How is erythropoiesis regulated?

A

1) The juxtatubular interstitial cells of the renal cortex detect hypoxia and increase levels of HIF1 alpha
As the HIF1 alpa levels increase, this increases EPO production.

2) As EPO increases, this increases production of erthryocytes.
3) As there are more erythrocytes, this decreases levels of hypoxia detected by kidney
4) The lower levels of hypoxia means less HIF1 alpha is produced and therefore less EPO is produced.

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11
Q

What anaemia can occur from changes in the bone marrow?

A

Conditions affecting specifically erythropoiesis in the bone marrow are described as pure red cell aplasia (PRCA)

Conditions affecting production of other cell types in addition to RBCs (white cells and platelets) is termed pancytopenia

The most common congenital PRCA is Diamond-Blackfan anaemia, which occurs due to reduced proliferation of erythroblasts. This is a rare condition, occurring in ~5 lives births/million.

Acquired PRCA can be classified as either primary (idiopathic – where no clear cause can be identified) or secondary (acquired as a result to exposure to a pathogenic agents such as a drug or infection)

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12
Q

What leads to HSC exhaustion?

A

When HSC DNA changes due to a chemical or genetic insult, the self-renewal process won’t happen and this means the pool of HSCs are not maintained. This can lead to pancytopenia.

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13
Q

Define Pancytopenia

A

A condition in which there is a lower-than-normal number of red and white blood cells and platelets in the blood. Pancytopenia occurs when there is a problem with the blood-forming stem cells in the bone marrow.

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14
Q

Define Aplastic Anemia

A

Aplastic anaemia is a serious condition affecting the blood, where the bone marrow and stem cells do not produce enough blood cells

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15
Q

Define Pure Red Cell Aplasia

A

Pure red cell aplasia (PRCA) is a rare disorder of blood production in which the bone marrow, the spongy tissue in the center of the bones, fails to function in an adequate manner resulting in anemia.

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16
Q

What is Haemolytic Anaemia

A

Haemolytic anaemia is caused by the premature destruction of function erythrocytes either by extrinsic or intrinsic mechanisms.

Anaemia will develop if the destruction is not balanced with the production of new erythrocytes

There are 2 reasons for erythrocyte destruction:
1. There is nothing fundamentally wrong with the erythrocyte, but they are destroyed by external pathological processes, such as drugs, toxins auto-antibodies or infection

  1. There is something intrinsically wrong with the erythrocyte so it is destroyed. This can be due to damage, absence of certain enzymes or abnormal types of haemoglobin
17
Q

What is auto immune haemolytic anaemia?

A

Autoantibodies are found when a patients’ immune system produces antibodies that recognize their own erythrocytes as foreign and mediate their destruction

Idiopathic AIHA accounts for approximately 50% of cases. Secondary AIHA can result from many other illnesses.

18
Q

What is drug induced AIHA

A

Drug-induced AIHA, though rare, can be caused by a number of drugs, including α-methyldopa and penicillin. The drug binds to macromolecules on the surface of the RBCs and acts as an antigen. Antibodies are produced against the RBCs, which leads to complement activation. This is one type of “penicillin allergy”.

19
Q

What are the secondary causes of AIHA?

A

The most common causes of secondary AIHA include lymphoproliferative disorders (e.g., chronic lymphocytic leukaemia, lymphoma) and other autoimmune disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis, scleroderma, crohn’s disease, ulcerative colitis).

20
Q

What are schisocytes?

A

Fragments of erythrocytes

21
Q

What is polychromasia?

A

Larger blue tinged reticulocytes.

22
Q

Spherocytes?

A

erythrocytes that are sphere-shaped rather than biconcave.

23
Q

Haemoglobinopathy

A

Haemoglobinopathies are autosomal co-dominant genetic defects resulting in abnormal structure of one of the globin chains of the haemoglobin molecules. Eg) Sickle Cell

24
Q

What is sickle cell anaemia?

A

Sickle cell anaemia is attribute to mutations in the beta-globin gene. Sickle cell erythrocytes are an abnormal shape, which affects their passage through the circulatory system, their ability to carry O2 and increased haemolysis.

Sickle Cell Anaemia can cause vaso-occlusive crises (vessel blockage) visceral sequestration crisis, aplastic and haemolytic crises.

25
Q

How many haemoglobin molecules does an erythrocyte contain?

A

around 640 molecules

26
Q

where is haemoglobin made?

A

It is made in the erythrocyte cytoplasm

27
Q

What micronutrients are needed to regulate erythrocyte function, especially for the metabolism of haem?

A

Iron, Vitamins B12 and B6 and folic acid.

28
Q

What can cause a lack of micronutrients needed for erythrocyte production?

A

malnutrition and malabsorption

29
Q

How is Iron Deficiency characterized?

A

Hypochromic (pale) microcytes. Lack of staining in centre of cell.

30
Q

What is the daily iron requirement of an infant and adult male?

A

1mg

31
Q

What intestinal factors contribute to reduced iron absorption?

A

The stomach - Gastritis, Gastric carcinoma …. etc
Upper and Lower GI - Duodenitis, Coeliac disease, crohns disease
surgery of above tissues

32
Q

What are sources of iron?

A 
Dark green leafy vegetables
iron fortified cereals
whole grains
beans
nuts
meat
33
Q

What makes absorption difficult?

A 
Tea and coffee
Calcium
antacids
PPIs
Wholegrain cereal
34
Q

What is sideroblastic anaemia?

A

The failure of Iron to be incorporated into haem in the erythrocyte precursor cells.

This can be due to the consequences of mutations or deletions of genes regulating the expression of key enzymes involved in haem synthesis.

The failure to incorporate iron into the correct areas, result in the formation of iron-rich mitochondria which surround the nucleus of the erythrocyte precursor as granules. These cells are termed sideroblasts.

35
Q

Where is haem synthesized?

A

Cytoplasm and mitochondria of erythrocyte progenitor cells.

36
Q

What vitamins are key regulators of haem production?

A

B6 B12 and Folate

B12/folate is also needed for DNA synthesis in erythrocyte proliferation

36
Q

What vitamins are key regulators of haem production?

A

B6 B12 and Folate

37
Q

Comparison of Different Anaemias on cell size

A
38
Q

Anaemias can be divided into microcytic, normocytic and macrocytic depending on what?

A

MCV - Mean cell volume

Block 4 Lectures (10 decks)

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