L06 - Classification and Lab Dx of Anemia Flashcards
Define Anaemia? Is it a disease?
Clinical condition: haemoglobin (Hb) 血紅素 concentration in red blood cell falls below the reference interval*
Specific for age, sex, race, altitude
Not a disease, But a manifestation/sign of the underlying disease
What are the 2 determinants of Hb conc.? What variation of these determinants = anemia?
Hb (gram) ÷ Volume of blood (dL / L)
1) Reduced mass of Hb/ normal plasma volume
2) Normal mass of Hb/ Reduced plasma volume
Factors that influence normal Hb concentration?
- Age: newborn = 19g/dL, Child = 10g/dL, Adult = 15g/dL
- Sex: lower Hb conc. in female
- Race
- Altitude: Higher alt = higher Hb conc.
Principle mechanism of anemia?
upset of the dynamic balance between normal red cell production and loss
Describe breakdown of RBC?
In tissue macrophages:
1) Heme > Iron and Biliverdin > Transferrin-Iron and Bilirubin into blood stream
2) Globulin > Amino acids
Unconjugated bilirubin > transformed into bilirubin glucuronides by liver to be excreted > excreted as stercobilinogen in feces or urobilinogen in urine
Breakdown products recycled or excreted
Classify anemia under 4 pathological classes?
- Production defect – bone marrow failure
- Destruction – haemolysis, blood loss
- Sequestration – hypersplenism
- Dilution – increase in plasma volume relative to red cell mass
Subclassification of anaemia caused by production defect?
1) Inadequate red cell production - upstream stem cell failure or stimulation failure or failure of maturation
2) Ineffective red cell production - Failure of maturation
List causes of inadequate RBC production.
a) Bone marrow defect:
i) Haematopoietic stem cells (e.g. aplastic anaemia)
ii) Production site defect (e.g. marrow infiltrative lesions)
b) Lack of humoural stimulation / erythropoietin (e.g. chronic renal failure)
c) Iron metabolism problem:
i) Iron deficiency anaemia
ii) Inability to use iron (sideroblastic anaemia)
List causes of ineffective RBC production.
A) Vit B12 metabolism problem
i) dietary B12 deficiency
ii) Inability to use Vitamin B12 (e.g. congenital transcobalamin II deficiency)
B) Involving globin metabolism: quantitative abnormality (Thalassaemia)
C) Myelodysplastic syndrome: common myeloid progenitor mutation with premature apoptosis
C) Megaloblastic anaemia: impaired nucleotide synthesis with abnormal maturation
Normal life span of RBC? Factors that influence life span?
Normal lifespan of red cells = 100-120 days – depends on:
- Membrane integrity
- Normal Haemoglobin structure
- Adequate supply of ATP (glycolysis and unloading)
- Adequate supply of reducing power (oxidative damadge)
What are the different root causes of increased red cell destruction?
Haemolysis:
1) Intrinsic/ intracorpuscular defect
2) Extrinsic/ extracorpuscular defect: Immune/ Non-immune haemolysis
3) Interaction between intra- and extracorpuscular factors
List some Intrinsic/ intracorpuscular defect of RBC?
– Red cell membrane defect
– Red cell enzyme defect (G6PD)
– Haemoglobin defect
List some Extrinsic/ extracorpuscular, Immune haemolysis defect of RBC?
Immune haemolysis (antibody-mediated):
1) Alloimmune (e.g. haemolytic transfusion reaction, haemolytic disease of the newborn)
2) Autoimmune (autoimmune haemolytic anaemia)
3) Drug-induced immune haemolysis
List some Extrinsic/ extracorpuscular, Non- immune haemolysis defect of RBC?
1) Mechanical damage (e.g. microangiopathic haemolytic anaemia, artificial heart valves)
2) Toxin
3) Infection (e.g. malaria – blackwater fever)
4) Burn
List one haemolytic disease due to Interaction between intracorpuscular and extracorpuscular factors ?
paroxysmal nocturnal haemoglobinuria
List some causes of RBC sequestration?
hypersplenism/splenomegaly from trapping / pooling of red cells, white cells, platelets:
1) Portal hypertension (e.g. due to liver cirrhosis, Hep B)
2) Haematological diseases (e.g. sickle cell anemia)
3) Uncommon: Chronic infections, Storage diseases
List some causes of Haemodilution?
- Pregnancy
- Fluid resuscitation after acute blood loss
Both increase plasma volume
Clinical features of anaemia?
Low Hb concentration → impaired O2 transport → tissue hypoxaemia → body compensation / decompensation
• Pallor
• Fatigue (tissue hypoxia)
Cardiopulmonary compensation:
• Palpitation
• Shortness of breath
Central and periphery pallor are both accurate in accessing the lack of O2 transport in anaemia. T or F?
False
Periphery = subject to temp change, not accurate
Central = accurate
What does the severity of anemic symptoms/ symptomatology depend on?
1) Extent to which haemoglobin concentration is lowered
2) Rate / rapidity of onset (e.g. acute =no time to compensate)
3) Adequacy of cardiopulmonary compensation (e.g. elderly = more severe)
Initial investigations techniques used to help guide Dx of anaemia?
1) Complete blood count (CBC):
- Cell count, Hb conc., Red cell indicies, Reticulocyte count, White cell and platelets
2) Examination of peripheral blood smear
> > Provide useful information on possible differential diagnosis, pathogenic mechanism for anaemia
List the variation in the size, shape and colour of blood cells seen under peripheral blood smear?
- Size: normocytic, microcytic, macrocytic, dimorphic (2 red cell populations)
- Variation in size = anisocytosis
- Colour (chromia): normochromic, hypochromic, polychromatic (indicates reticulocytosis)
- Variation in shape = poikilocytosis
List the RBC indicies obtained in CBC?
- Haemoglobin (HGB)
- Mean cell volume (MCV)
- MCH (follows MCV normally)
- Red cell distribution width (RDW)
- Mean cell haemoglobin concentration (MCHC)
Which RBC indicies is the most useful for DDx of anaemia after HGB?
Mean cell volume (MCV)
