Red Blood Cell Production and Survival Flashcards

1
Q

Describe red blood cell production.

A

1) HEMOCYTOBLAST (Stem Cell)
2) PROERYTHROBLAST (Committed Cell)
3) EARLY ERYTHROBLAST
4) LATE ERYTHROBLAST
5) NORMOBLAST
6) RETICULOCYTE
7) ERYTHROCYTE

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2
Q

Describe an example (the kidney) of the hormonal control of Erythropoiesis.

A

1) Stimulus: hypoxia due to decreased RBC count, decreased amount of haemoglobin or decreased availability of O2.
2) There are reduced levels of O2 in the blood
3) The paratubular cells in the kidney (and liver, to a smaller extent) release erythropoietin.
4) Erythropoietin stimulates redbone marrow.
5) Enhanced erythropoietin increases RBC count.
6) This increases the O2-carrying ability of the blood.
7) Homeostasis is restored.

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3
Q

What is required for erythropoiesis (red blood cell production)?

A
  • Fe2+
  • Vitamin B12
  • Amino acids (to make globin)
  • Folic Acid
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4
Q

Describe iron.

A

SOURCES: meat, eggs, vegetables, dairy foods

Gastric secretion (HCl) and ascorbic acid help absorption.

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5
Q

List some causes of an iron deficiency.

A

DECREASED UPTAKE OF IRON:

  • inadequate intake
  • malnutrition

INCREASED DEMAND:

  • pregnancy
  • growth spurt

INCREASED LOSS:

  • GI bleed
  • excess less in menses
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6
Q

Describe Vitamin B12 and Folic Acid.

A

Both are essential for RBC maturation and DNA synthesis.

  • both needed for the formation of thymidine triphosphate.
  • B12 is the coenzyme for methionine synthase in methylation of homocysteine to methionine

A deficiency in either of them causes abnormal and diminished DNA, leading to failure of nuclear maturation.

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7
Q

What happens in Folate and B12 deficiencies?

A

Megaloblastic anaemia can occur, with macroovalocytes and hypersegmented neutrophil.

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8
Q

List some causes of a Vitamin B12 deficiency.

A

INADEQUATE INTAKE:
- vegans

ABSORPTION DEFECT:

  • tropical sprue (malabsorption disease, flat villi, affects the small intestine)
  • coeliac disease
  • blind loop syndromes (small intestine bacterial overgrowth, compete for B12)

IF DEFICIENCY (INTRINSIC FACTOR DEFICIENCY, IF needed for B12 absorption):

  • pernicious anaemia
  • Crohn’s disease (GI tract affected)
  • gastrectomy and other causes (where parietal stomach cells are affected, so can’t make IF)
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9
Q

List some causes of a Folate deficiency.

A

INADEQUATE UPTAKE:
- poor nutrition

ABSORPTION DEFECT:

  • coeliac disease
  • Crohn’s disease
  • tropical sprue

INCREASED DEMAND/LOSSES:

  • pregnancy
  • haemolysis
  • cancer

DRUGS;
- anticoagulants (inhibit folate absorption)

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10
Q

List some other causes of the failure of RBC production.

A
  • RENAL DISEASE: ineffective erythropoiesis
  • REDUCED BONE MARROW ERYTHROID CELLS
  • APLASTIC ANAEMIA
  • MARROW INFILTRATION BY LEUKAEMIA/OTHER MALIGNANCIES: it infiltrates the bone marrow and inhibits RBC production
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11
Q

What are three ways in which you can classify haemolytic anaemia?

A
  • HEREDITARY/ CONGENITAL or ACQUIRED
  • INTRINSIC FACTORS or EXTRINSIC FACTORS
  • INTRAVASCULAR or EXTRAVASCULAR
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12
Q

Describe acquired haemolytic anaemia.

A

IMMUNE:

  • Autoimmune (when the body itself fights red cells)
  • Alloimmune (when given blood fights the body)
  • Drug-induced (when drugs induce the fighting)

NON-IMMUNE:

  • Red cell fragmentation (when, for example, a heart valve is replaced, and when red blood cells flow through it, they get fragmented)
  • Infection (eg. malaria)
  • Secondary (eg. liver/ kidney diseases)
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13
Q

Describe some hereditary causes of haemolytic anaemia.

A

HAEMOGLOBINOPATHIES:

  • sickle cell diseases
  • thalassaemias

RED CELL ENZYMOPATHIES:

  • G6PD deficiency
  • PK deficiency

RED CELL MEMBRANE DISORDERS:

  • hereditary spherocytosis (RBCs are spherical)
  • hereditary elliptocytosis (RBCs are elliptical, oval-shaped)
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14
Q

Describe Sickle Cell Disease.

A

There is a group of haemoglobin disorders with an inherited sickle β-globin gene. Sickle Cell Anaemia is homozygous (Hbss), and it is the most common of all Sickle Cell Diseases.
The normal β-globin gene has the nucleotides GAG, which codes for glutamic acid. In the sickle β-globin gene, the A is replaced with a T, changing the amino acid made to Valine.

Other than Sickle Cell Anaemia, there are other types of Sickle Cell Diseases, which are heterozygous:

  • HbS/βthal
  • HbSC
  • HbSD
  • HbSE

In sickle cell anaemia, you will see red blood cells shaped as a sickle. You will also see some target cells.

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15
Q

Describe thalassaemia.

A

There are two types of thalassaemia, β thalassaemia and α thalassaemia.

β THALASSAEMIA:
The loss of one β-chain causes mild microcytic anaemia (a thalassaemia trait). The loss of both β-chains causes thalassaemia major.
This means that an excess of α-chains precipitate into the erythroblasts, causing haemolysis and ineffective erythropoiesis.

α THALASSAEMIA:
Here, there can be a loss of one, two, three or four α-chains.

In thalassaemia, you will find red blood cells called target cells. You will also see cells that look like teardrops.

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16
Q

List (and briefly describe) the two main red cell enzymes.

A

The two main red cell enzymes are:

  • Glucose-6-Phosphate Dehydrogenase (G6PD)
  • Pyruvate Kinase (PK)

They support two main metabolic pathways:

  • Pentose Phosphate Pathway
  • Glycolytic Pathway
17
Q

What happens in a G6PD deficiency?

A

It is a metabolic abnormality. In it, NADPH and GSH generation is impaired.
Acute haemolysis occurs on exposure to oxidant stress, such as oxidative drugs, fava beans (broad beans) or infections.
Haemoglobin precipitates, causing Heinz bodies (red blood cells with denatured haemoglobin) to be seen.

In it, you will see blister/basket cells, which are red blood cells with the haemoglobin on one side.

A G6PD deficiency is most commonly known as enzymopathy. It is highly prevalent in places with high malaria rates, as the patients infected with malaria then aren’t affected as severely, and are able to survive it. Thus, it is evelutionarily beneficial.

18
Q

What happens in a PK deficiency?

A

ATP-depleted cells lose a large amount of potassium and water, and become dehydrated and rigid.
This happens because cation pumps fail to function. This causes chronic, non-spherocytic haemolytic anaemia. The excess haemolysis leads to jaundice and gallstones.