Red Cells 2 Flashcards

1
Q

How is the normal range of something derived?

A
  • Subjects who don’t have disease
  • Normal distribution
  • Mean +/-2 standard deviations
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2
Q

What are some factors that influence the normal range?

A
  • Age
  • Sex
  • Ethnic origin
  • Time of day sample taken
  • Time to analyse
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3
Q

What are the reference ranges for Hb?

A
  • Male 12-70
    • 140-180
  • Male >12
    • 116-156
  • Female 12-70
    • 120-160
  • Female >70
    • 108-143
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4
Q

Describe the clinical features of anaemia?

A
  • Tiredness
  • Breathlessness
  • Swelling of ankles
  • Dizziness
  • Chest pain
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5
Q

What does the presentation of anaemia depend on?

A
  • Age, speed of onset, and Hb level
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6
Q

What are some potential clinical features of anaemia that could be related to the underlying cause?

A
  • Evidence of bleeding
    • Menorrhagia
    • Dyspepsia, PR bleeding
  • Symptoms of malabsorption
    • Diarrhoea
    • Weight loss
  • Jaundice
  • Splenomegaly/lymphadenopathy
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7
Q

Describe the approach to determining the cause of anaemia?

A

Can be due to:

  • bone marrow
  • red cell
  • destruction/loss
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8
Q

Describe the aetiology of anaemia due to bone marrow problems?

A

Cellularity

Stroma

Nutrients

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9
Q

Describe the aetiology of anaemia due to red cell problems?

A

Membrane

Haemoglobin

Enzymes

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10
Q

Describe the aetiology of anaemia due to destruction/loss?

A

Blood loss

Haemolysis

Hypersplenism

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11
Q

What does MCH stand for?

A

Mean cell haemoglobin

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12
Q

What does MCV stand for?

A

Mean cell volume (cell size)

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13
Q

What are red cell indices?

A

Calculations that provide information on the physical characteristics of RBCs

  • Automated measurement of red cell size and haemoglobin content
    • MCH = mean cell haemoglobin
    • MCV = mean cell volume (cell size)
  • Gives morphological description of anaemia and clue to cause
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14
Q

What are the 3 morphological describers for anaemic cells?

A
  • Hypochromic microcytic anaemia
    • Small, pale cells
  • Normochromic normocytic anaemia
    • Normal size and normal haemoglobin content in average cell
  • Macrocytic anaemia
    • Big, red cells
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15
Q

What do the cells look like in hypochromic microcytic anaemia?

A

Small, pale cells

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16
Q

What do the cells look like in normochromic normocytic anaemia?

A
  • Normal size and normal haemoglobin content in average cell
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17
Q

What do the cells look like in macrocytic anaemia?

A
  • Big, red cells
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18
Q

For each morphological describer of the cells in anaemia, what follow up investigations should be done?

A
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19
Q

Describe the investigations for anaemia?

A

Red cell indices and blood film

Then depending on the morphology of cells (look at picture)

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20
Q

Describe the aetiology of hypochromic microcytic anaemia?

A

Low serum ferritin - iron deficiency

Normal/increased serum ferritin - thalassaemia, secondary anaemia

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21
Q

Where is iron absorbed?

A

Absorbed in duodenam (Fe2 better than Fe3)

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22
Q

Describe the process of iron being absorbed?

A
  1. Bound to mucosal ferritin and sloughed off
  2. Or transported across the basement membrane by ferroportin
  3. Then bound to transferrin in plasma
  4. Stored as ferritin – mainly in liver
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23
Q

What protein transports iron across the basement membrane?

A

Ferroportin

24
Q

What is iron bound to in the plasma?

A

Transferrin

25
Q

What is iron stored as?

A

Ferritin (mainly in liver)

26
Q

What is hepciden?

A
  • Synthesised in hepatocytes in response to increased iron levels and inflammation
  • Blocks ferroportin so reduces intestinal iron absorption and mobilisation
27
Q

Is iron deficiency anaemia a diagnosis?

A

Is not a diagnosis, establish the cause:

  • History
    • Dyspepsia (Gi bleeding)
    • Other bleeding (such as menorrhagia)
    • Diet (particularly children and elderly)
    • Increased requirement (pregnancy)
  • Examination
    • Koilonychia
    • Atrophic tongue
    • Angular cheilitis
28
Q

Describe the aetiology of iron deficiency?

A
  • GI blood loss
  • Menorrhagia
  • Malabsorption
29
Q

What is the commonest cause of anaemia?

A

Iron deficiency

30
Q

Describe the management of iron deficiency?

A
  • Correct deficiency
    • Oral iron usually sufficient, if not use IV iron
  • Correct the cause
    • Diet
    • Ulcer therapy
    • Gunae interventions
    • Surgery
31
Q

Describe the aetiology of normochromic normocytic anaemia?

A
  • If reticulocyte count increased
    • Acute blood loss
    • Haemolysis
  • If reticulocyte count normal or low
    • Secondary anaemia
      • Hypoplasia
      • Marrow infiltration
32
Q

Describe the typical morphology of red cells in secondary anaemia?

A
  • 70% normochromic normocytic
  • 30% hypochromic microcytic
33
Q

Describe the pathophysiology of secondary anaemia?

A
  • Defected iron utilisation
    • Increased hepcidin in inflammation
    • Ferritin normal or elevated (an acute phase reactant)
34
Q

Describe the aetiology of secondary anaemia?

A
  • Identifiable underlying disease
    • Infection
    • Inflammation
    • Malignancy
35
Q

Describe the pathophysiology of haemolytic anaemia?

A
  • Accelerated red cell destruction (decreased Hb)
  • Compensation by bone marrow (increased reticulocyte count)
  • How anaemic you are depends on this balance
36
Q

What are the 2 kinds of haemolysis?

A
  • Extravascular is physiological, but could be pathological
  • Intravascular is pathological
37
Q

Is intra or extra-vascular haemolysis always pathological?

A

Intra-vascular

38
Q

Describe the aetiology of haemolytic anaemia?

A
  • Congenital
    • Hereditary spherocytosis (HS)
    • Enzyme deficiency (G6PD deficiency)
    • Haemoglobinopathy (HbSS)
  • Acquired
    • Extravascular
      • Auto-immune haemolytic anaemia
    • Intravascular
      • Mechanical (artificial valve)
      • Severe infection
      • PET
39
Q

For haemolytic anaemia, are immune and non-immune causes usually extra or intra-vascular?

A
  • Immune causes are mostly extravascular
  • Non-immune causes are mostly intravascular
40
Q

What investigation can be done to determine if haemolysis is from an immune cause?

A
  • Direct antiglobulin test
    • Detects antibody or complement on red cell membrane
    • Reagent contains either anti-human IgG or anti-compliment
      • Binds to Ab (or compliment) on red cell surface and causes agglutination in vitro
    • If positive – immune mediated
    • If negative – non-immune mediated
41
Q

Some antibodies can only bind at certain temperatures, what is an implication of this for haemolytic anaemia?

A

Allows the cause to be guessed

42
Q

Describe the different between intra and extravascular haemolysis on blood film?

A
  • Extravascular
    • Spheres
  • Intravascular
    • Red cell fragments, “schistocytes”
43
Q

What investigations can be done to determine if the patient is haemolysing?

A
  • FBC, reticulocyte count, blood film
  • Serum bilirubin (direct/indirect), LHL
    • High
  • Serum haptoglobin
    • Low
44
Q

Describe the management of haemolytic anaemia?

A
  • Support marrow function
    • Folic acid
  • Correct cause
    • Immunosuppression if autoimmune
      • Steroids
      • Treat trigger
    • Remove site of red cell destruction
      • Splenectomy
    • Treat sepsis, leaky prosthetic valve, malignancy ect if intravascular
  • Consider transfusion
45
Q

Describe the aetiology of macrocytic anaemia?

A
  • B12/folate deficiency (most common cause)
  • Alcohol
  • Drugs
  • Disordered liver function
  • Hypothyroidism
  • Myelodysplasia
46
Q

What investigation should be done after discovering macrocytic anaemia?

A

B12/folate assay

47
Q

Describe the pathophysiology of megablastic anaemia?

A
  • B12/folate deficiency
48
Q

Describe the aetiology of megaloblastic anaemia?

A
  • Of B12 deficiency
    • Pernicious anaemia
    • Gastic/ileal disease
  • Folate deficiency
    • Dietary
    • Increased requirements (haemolysis)
    • GI pathology
49
Q

Describe the presentation of megaloblastic anaemia?

A
  • Anaemia
  • Neurological symptoms
    • Subacute combined degeneration of the cord in B12 deficiency
50
Q

Describe the treatment of megaloblastic anaemia?

A
  • Replace vitamin
  • B12 deficiency
    • B12 intramuscular injection
    • Loading dose then 3 monthly maintenance
  • Folate deficiency
    • Oral folate replacement
51
Q

Describe the mechanism of vitamin B12 absorption?

A
  • Dietary B12 binds to intrinsic factor secreted by gastric parietal cells
    • If do not have this intrinsic factor cannot absorb
  • B12-IF complex attaches to specific IF receptors in distal ileum
  • Vitamin B12 bound by transcobalamin II in portal circulation for transport to marrow and other tissues
52
Q

What is intrinsic factor secreted by?

A

Gastric parietal cells

53
Q

What is vitamin B12 bound to when in portal circulation for transport to marrow and other tissues?

A

Transcobalamin II

54
Q

Describe the aetiology of pernicious anaemia?

A
  • Autoimmune disease
55
Q

Describe the pathophysiology of pernicious anaemia?

A
  • Antibodies against intrinsic factor (diagnostic)
56
Q

What is the commonest cause of B12 deficiency?

A

Pernicious anaemia

57
Q

Describe the presentation of pernicious anaemia?

A
  • Takes 1-2 years to develop
  • Anaemia
  • “Lemon yellow” tinge
    • Bilirubin, LDH
    • Red cells friable
  • Hypersegmentation of neutrophils