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509 - Cellular and Transfusion Science > Heamatopoiesis and Anaemias > Flashcards

Heamatopoiesis and Anaemias Flashcards

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1
Q

What ancestral cell do all blood cells have?

A

Multipotent stem cell (MSC)

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2
Q

Outline HSCs

A
  • Occur 1:5000 in bone marrow
  • Have the capacity to give rise to non-self renewing populations that generate multiple terminally-differentiated cell types
  • Contain efficient membrane pumps
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3
Q

State the two niches within bone marrow where stem cells renew and differentiate

A

Osteoblastic niche (endosteal surface)
Vascular niche (involving sinusoidal blood vessels)

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4
Q

What do each stem cell niche do?

A

Osteoblastic: maintains quiescence, harbours long term HSC

Vascular: Supports proliferation, differentation, mobalisation of short term HSC

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5
Q

What factors control haematopoiesis (blood component formation)?

A

Extrinsic factors (soluble growth factors)
Intrinsic factors (transcription factors)

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6
Q

State and outline some important transcription factors

A
  • Runx1: required for normal haematopoiesis
  • Ikaros: regulate immune system development
  • Pax5, E2A, EBF
  • Notch-1, GATA-3: T cell development
  • GATA-1: essential for erythroid and platelet forming cells
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7
Q

State the key steps in erythropoiesis

A
  1. Proerythroblast (first committed RBC)
  2. Basophilic erythroblast (nucleus shrinks, cytoplasm beckmes more basophilic due to ribosome presence)
  3. Polychromatophilic erythroblast (produce more haemoglobin, cytoplasm takes up baso + eosin stains)
  4. Orthochromatohilic erythroblast (excludes nucleus)
  5. Reticulocyte (cytoplasm contains polyribosomes, enters circulation)
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8
Q

Where does erythropoiesis occur?

A

In early fetus: yolk sac, spleen, liver
After birth: bone marrow

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9
Q

State an example of an extrinsic factor.

A

Erythropoietin

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10
Q

Outline Erythropoietin

A
  • Hormone, produced in fibroblast-like cells
  • 165 animo acid glycoprotein
  • 4 carbohydrate chains
  • Anti-apoptotic (prevents apoptosis)
  • Levels increase when haemoglobin levels decrease
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11
Q

How can erythropoietin levels help clinically?

A
  • High levels indicate anemia (unless it is due to renal failure with a tumour)
  • Low levels in renal disease or polycythemia vera
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12
Q

What family of proteins meditate the effect of growth factors?

A

Janus-associated kinase (JAK) proteins

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13
Q

Describe RBC characteristics

A
  • Anucleate (increases flexsbility and O2 carrying capacity, but reduces life span)
  • Highly flexible
  • Biconcave discs
  • 8μL diameter
  • 80-100 fL volume
  • Average 120 day lifespan
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14
Q

State 4 pathways involved in RBC metabolism

A

Pentose phosphate pathway
Methemoglobin reductase pathway
Luebering-Rapaport Bypass
Lactic acid fermentation

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15
Q

How do RBCs make ATP?

A

Embden Meyerhof pathway (glycolysis of glucose to pyruvate, forming ATP and NADH/lactic acid fermentation on pyruvate, forming ATP, NAD+, lactate)
Pentose phosphate pathway (important in generating NADPH, keeps haemoglobin in ferrous state)

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16
Q

What enzymes regulates pentose phosphate pathway to reduce oxidative stress?

A

glucose-6-phosphate dehydrogenase

17
Q

How does anemia occur?

A

Lowered production of RBCs
Increased destruction/loss of RBCs

18
Q

What can decrease RBC production?

A
  • Disturbance of Hb synthesis
  • Disturbance of DNA synthesis
  • Unknown/multiple mechanisms
19
Q

What can increase RBC loss/destruction?

A

Intrinsic (inherited) abnormality:
- Membrane defect
- Enzyme defect
- Globin abnormalities

Extrinsic (aquired) abnormality:
- Blood loss
- Mechanical
- Chemical/physical
- Infection
- Antibody mediated
- Hyperspleenism

20
Q

How are anemias diagnosed?

A

Physical examination
Full blood count
Reticulocyte (immature RBCs) count
Bone marrow biopsy

21
Q

What do MCV, MCH, and MCHC mean?

A

MCV: average volume of red cells-size
MCH: average content (mass, weight) of Hb/RBC
MCHC: average weight of haemoglobin per unit volume of red cell

22
Q

State 4 types of anemia:

A
  • Normocytic: normal sized RBCs, low in number
  • Haemolytic: RBCs destroyed faster than synthesised
  • Macrocytic: abnormally large cells, normal Hb
  • Microcytic: smaller than usual due to reduced Hb
23
Q

How is normocytic anemia classified?

A
  • Reduced Hb and RBC counts
  • MCV = normal (80-100 fL)
  • Due to: internal/external bleeding or bone marrow faulure
24
Q

Outline anemia due to hemorrhage

A

Acute (extrinsic):
- Hb normal immediately after blood loss
- Compensatory mechanisms kick in 24h later
- Fluid enters blood to restore blood volume, haemodilution causes anaemia
- Treat by stopping blood loss, transfusion

Chronic (extrinsic or intrinsic):
- Anaemia develops is normocytic and normochromic
- Iron stores depleted
- Treat by stopping bleeding and giving iron
- May need transfusion

25
Q

Define normochromic and normocytic

A

Normochromic: RBCs have normal red colour

Normocytic: RBCs are normal size

26
Q

Outline the types of aplastic anaemia

A

RBC aplasia:
- Reduced/increased erythroblasts
- Congenital

Acquired PRBCA:
- Primary or secondary cause
- E.g., infections like HIV
- Autoimmune disease

27
Q

Outline macrocytic anaemia

A
  • DNA synthesis disorder (incorrect division leads to larger cells)
  • B12/folate deficiency
  • Due to malabsorption or diet
  • Reduced Hb, increased MCV
  • normal + neurological symptoms
28
Q

Outline polycythemia vera and erythemia

A

Polycythemia vera:
- increase in all blood cells
- unknown stem cell mutation
- JAK2 mutation

Erythemia:
- increase in RBCs

29
Q

Outline haemolytic anaemia

A
  • An increase in RBC destruction
  • Normal life span shortened
  • Removed by spleen
  • Hyperspleenism
  • Increased haemolysis, anaemia symptoms (doesn’t always lead to anaemia)
30
Q

Compare intravascular and extravascular haemolysis

A

Intravascular:
- RBCs destroyed in circulation
- Hb release into plasma
- May be immune mediated
- Iron causes damage in blood
- Free Hb binds to haptoglobin, reducing levels

Extravascular:
- Premature RBC destruction in spleen/bone marrow
- RBC removed by macrophages
- Haem breakdown in macrophage generated bilirubin
- Bilirubin released, binds to albumin (liver) to excrete in bile
- Unconjugated bilirubin levels rise, leads to jaundice

31
Q

How to diagnose increased haemolysis

A
  • Morphology of RBCs
  • Hb plasma levels
  • Bilirubin levels
  • Haptoglobin levels
  • Hb in urine levels
  • Increased erythropoiesis
32
Q

Discuss RBC enzyme defects

A
  • Glucose-6-Phosphate Dehydrogenase
  • Causes increase in oxidative stress
  • G6PD gene sex linked disorder (X)

509 - Cellular and Transfusion Science (15 decks)

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