Anaemias And Haematopoiesis Flashcards

1
Q

What is Haematopoiesis?

A

Its the production of RBC, WBC and platelets from undifferentiated stem cells. RBCs are produced under anaemia/hypoxia, WBC are produced in response to systemic infection and Platelets are produced due to thrombocytopenia.

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2
Q

What is erythropoiesis and where is it initiated?

A

Formation of erythrocytes from pluripotent stem cells. They are produced from bone marrow and is initiated by erythropoietin which is produced in the kidneys.

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3
Q

How is erythropoiesis regulated?

A

When Hb levels decrease O2 delivery to the kidneys decreases and the kidneys produces more EPO, hence the bone marrow produces more RBCs. EPO prevents apoptosis of eryhtroid precursor cells which allows these cells to proliferate and mature into RBCs.

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4
Q

How is iron absorbed?

A

There are 2 types of absorbable dietary iron: Heme iron from animal-based foods, more efficiently absorbed and non-heme iron plant based foods and iron-fortified foods, less well absorbed. Its absorbed in the ferrous (Fe2+) state.

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5
Q

How does iron move across intestinal mucosal cells?

A

By active transport of Fe2+ by divalent metal transporter. And by absorption of iron complexed with heme by heme-carrier protein 1, split from heme inside cells.

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6
Q

How is iron transported and stored?

A

Iron (Fe3+) is transported by transferrin. It transports iron to marrow for incorporation into Hb/storage sites, marrow, liver, spleen. Transferrin receptors circulate and attach to cells in need of iron. Iron is stored within macrophages as ferritin or hemosiderin.

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7
Q

What do we test for in laboratory evaluations?

A

Serum Iron: concentration iron bound to transferrin in circulation

Total Iron-Binding Capacity
Measurement of iron-binding capacity of serum transferrin. Proportional to amount of transferrin available in blood to bind iron.

Percentage transferrim saturation:
Ratio of serum iron to total iron-binding capacity. Measure the extent to which iron-binding sites on tranferrin are occupied by iron molecules.

Serum ferritin:
Indicates amount of iron stored in liver, spleen and marrow.

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8
Q

What is anaemia?

A

Its a group of diseases characterised by decreased volume RBC or HB, resulting in reduced oxygen carrying-capacity of blood.

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9
Q

What are some signs and symptoms of anaemias?

A

Fatigue, Headache, Dizziness, Palpitations, Tachycardia, Pallor, Cold hands.

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10
Q

How is one diagnosed with anaemia?

A

Based on patient history, physical examination and lab testing. FBC (Full Blood Count) and bone marrow status, RBC production, RBC size/shape.

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11
Q

How to classify anaemia based on RBC size and HB?

A

We do it through the Mean Corpuscular Volume, Macro,Normo and Microcytic.
And through Mean corpuscular haemoglobin, Hyper, Normo and Hypochromic levels.

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12
Q

What are the causes of anaemia?

A

Iron deficiency, megaloblastic (folate/Vit B12), pernicious (Vit B12 deficiency due to lack to intrinsic factor), anaemia of inflammation, Haemolytic (increased haemolysis of RBCs), aplastic (bone marrow damage), sickle cell anaemia (sickle shaped RBC)

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13
Q

What are some causes and factors leading to iron deficiency anaemia?

A

Depends on sex, age, genetics.
Causes include: inadequate dietary iron intake, inadequate iron absorption, increased iron demand (pregnant women), blood loss (menstruating women).

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14
Q

What are some lab finding of Iron Deficiency Anaemia?

A

Low serum iron, low ferritin, High TIBC (to try and compensate for low iron)
Low Hb and Hct
Low MCV (microcytic)

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15
Q

What is megaloblastic anaemia and what are some causes of vitamin B12 deficiency?

A

Caused by vitamin B12 and or folate deficiency (can coexist). Elevated MCV (macrocytic) and elevated MCH. Inadequate dietary intake, malabsorption (pernicious anaemia)
Certain medicines, metformin,PPI, histamine-2 receptor agonists.

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16
Q

What is anaemia of inflammation?

A

Normal MCV and MCH, elevated ferritin. It has multifactorial pathogenesis. Diminished EPO response, impaired proliferation of erythroid progenitor cells, disturbed iron homeostasis. Inflammation increases hepcidin, which inhibits iron absorption and prevents iron release from storage site.

17
Q

What is haemolytic anaemia?

A

Anaemia due to haemolysis of RBCs. It causes High reticulocyte (immature RBCs) count, low haptoglobin (transporter of iron when RBCs are destroyed)

Haemolysis may be caused by, diclofenac, cephalosporins, dapsone, G6PD deficiency, cell membrane abnormalities, sickle cell anaemias, thalassaemia.

18
Q

When should iron be responsed?

A

Treatment evaluated after 3 weeks for increased reticulocyte count and Hb

19
Q

When is oral iron contraindicated?

A

Iron overload states: haemochromatosis, chronic alcoholism, liver impairment and porphyria cutanea tarda.

20
Q

What are some cautions of iron?

A

Geriatrics: may cause constipation with faecal impaction. In paediatrics, accidental iron poisoning

21
Q

What are some food and drug interactions?

A

Food: tea, coffee, eggs, dairy products.
Drugs: decrease iron absorption, antacids, ca, mg,al
Absorption increased by iron: methyldopa and tetracyclines.

22
Q

When is parenteral iron indicated?

A

Oral iron is expected to be ineffective. Oral iron is not tolerated. Pregnant patient(>36 weeks) with iron deficiency anaemia.

23
Q

What are some adverse effects of parenteral iron?

A

Metallic taste, headache, nausea, rash, injection site reaction.

24
Q

What are some indications of oral folic acid?

A

Treatment of folate deficiency, prophylaxis is pregnancy, breast-feeding, patients taking isoniazid, methotrexate and sulfasalazine.

25
Q

What is one key thing to note with oral folic acid?

A

Folic acid should not be given alone with megaloblastic anaemia (MA due to vitamine B12 deficiency and folate deficiency can coexist. If only folic acid is given, haematological symptoms and mask neurological symptoms of vitamin B12 deficiency.

26
Q

What are examples of EPO and the mechanism of action

A

Epoetin alfa, Epoetin beta, Darbepoetin alfa. Treatment of anaemia of chronic renal failure. MOA: The same action as endogenous EPO –> stimulates erythropoiesis in bone marrow

27
Q

What are some contraindications and adverse effects?

A

Contraindications: uncontrolled hypertension, meyloid malignancy, hypersensitivity, untreated iron deficiency
Adverse effects: hypertension, headaches, injection site reactions.

28
Q

What are other haematopoietic growth factors and their MOA?

A

Filgrastim, Pegfilgrastim. Bind to G-CSF receptor on surface of myeloid progenitor cells in bone marrow. Stimulate differentiation and proliferation of progenitors of neutrophil lineage. Increase production production and neutrophils from bone marrow.

29
Q

What is the indication and MOA of deferoxamine?

A

Acute iron poisoning, long-term treatment of chronic iron overload. Chelates with excess ferric iron to form a stable iron complex, complex is excreted in urine.