Week 12 + Flashcards
(20 cards)
WEEK 12
Biochemical Assessment for Anemia
CASES - slide 3 - READ
What do these tests mean?
–> Hematological tests
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VISUAL - slide 5 - review
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- Hemoglobin (Hb)
- Hematocrit (Hct)
- Mean corpuscular volume (MCV)
- Mean cell hemoglobin (MCH)
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Sensitivity
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Specificity
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- What nutr deficiencies cause anemia?
[anemia = low hemoglobin levels]
(name all 5)
- What else could cause anemia?
_______, involves mainly: 1 & 2
- Also affected by: (name all 4)
SO - VIEW cut off values - slide 7
- Most commonly used in screening test for anemia (g/L)
- Easy and inexpensive
Sens
- Low - detects only anemia, not less serious deficiencies
Spec
- Poor- may be due to ANY type of anemia
- 1 Iron, 2 Folate, 3 Vit B12, 4 Copper, 5 Protein
- ___malaria___ : 1 increased removal of circulating erythrocytes & 2 decreased production of erythrocytes in the bone marrow
- 1 Race, 2 Pregnancy, 3 Altitude, 4 Smoking
[preg - more fluid = dilution = shows lower Hb levels] [smoking - more oxidation replaced my CO - and replaces the O on Hb] [altitude - less O higher u are - Hb compensates - body produces more Hb]
Hematocrit (Hct)
- Volume % of RBCs in blood =
- Rise and fall in parallel to __
- Combined with Hb, most commonly used…
Sensitivity -
Specificity -
= Red cell volume / total blood volume (as a %)
- to Hb
- … used test for screening for anemia (cheap and easy to do)
- low as per Hb
- low as per Hb
Mean Corpuscular Volume
- An index derived from Hb, Hct and RBC count
MCV (fL; femtoliters/cell) = hematocrit (volume fraction)/RBC count (1012/L)
–> Reflects ____
–> Requires…
Sensitivity -
Specificity -
VISUAL - slide 10 ** VIEW
microcytic - iron/vit B6 deficiency (Low MCV)
macrocytic - B12 or folic acid deficiency (High MCV)
SUMMARY - slide 11
–> Reflects the average size of RBCs
–> … electronic cell counter for best determination of RBC count
Sensitivity - MCV decreases only with severe iron deficiency
Specificity - good as it differentiates between microcytic and macrocytic anemias
Mean Cell Hemoglobin
- Hb content of an individual red cell
MCH (pg; picograms/cell) = Hb (g/L)/RBC count (1012/L)
Sensitivity -
Specificity -
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What causes microcytic and macrocytic anemias?
MICRO -
MACRO -
[Lead - break down of cells
Macro - systemic inflammatory impacts RBC homeostasis & structure/formation of Hb]
** VIEW slide 14 & google doc pg 5 for chart filled in **
Inflammation = normocytic but coming to light in research as a problem
Sens - more sensitive than MCV
Spec - helps distinguish between micro and macrocytic anemia
- Low in iron-deficiency anemia (microcytic anemia) [HYPOchromic anemia - pale RBC]
- High in macrocytic anemias of both vitamin B12 and folate deficiency [HYPERchromic anemia - higher than normal Hb per cell]
MICRO - iron deficiency, lead poisoning, Vit B6 deficiency
MACRO - Folate deficiency, B12 deficiency, some other disease such as liver disease or COPD
Back to case studies
What do they have?
Shirley: Microcytic anemia - iron or B6 deficiency [cause of low MCV/MCH]
Jeff: Macrocytic anemia - B12 or folate deficiency [Jeff has high MCV/MCH based on cut-off values above]
WHY shirley has MICROcytic anemia?
Stages of Iron deficiency - divided into 3 stages depending on severity:
1
2
3
* most common anemia cause in the world (iron deficiency anemia) *
STAGE 1
Iron Depletion
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STAGE 2
Iron Deficient Erythropoiesis
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1 Fe depletion
2 Fe deficient erythropoiesis
3 Fe deficiency anemia
- Progressive reduction in Fe stores
(Ferritin levels are lower - (ferritin is major form of iron stored in the body)) - Fewer stores but no functional changes (physiological)
- This stages indicates marginal balance that could progress to more severe deficiency with physiological consequences
- Sustained reduction in plasma Fe supply to the bone marrow to make erythrocytes
- Body Fe stores are completely depleted
- This stage is characterized by biochemical changes, which reflect a lack of supply for normal production of hemoglobin and RBCs (but no anemia yet!)
STAGE 3
Iron Deficiency Anemia
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- Most advanced stage of iron deficiency in which normal red cells are replaced by hypochromic microcytic cells
- Depletion of iron stores, decrease in circulating iron, and decreased Hb production
[Main feature is decreased Hb concentrations in RBCs, due to restriction of iron supply to the bone marrow - Iron deficiency is the most common cause of anemia
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Useful to distinguish…
- Serum Iron
- Total Iron binding capacity
- Transferrin saturation
- Serum ferritin (Fe)
- Zinc Protoporphyrin (ZnPP) and free erythrocyte protoporphyrin (FEP)
- Transferrin receptors (TfR)
(TIBC)
- Reflects iron in transit (serum iron is bound to transferrin)
- Each molecule of transferrin binds 1 or 2 atoms of Fe
- TIBC is a measure of free binding sites on transferrin
- Transferrin saturation is the number of “full” transferring molecules
… to distinguish stages of iron deficiency - usually stage 2!
Serum Iron, Total Iron binding capacity (TIBC) & Transferrin Saturation CON’d
–> In the 2nd stage of iron deficiency…
Sensitivity
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Specificity
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[Transferrin receptors???] - found on the organ - take iron from transferrin - more receptors they have they are trying to compensate - reflect deficiency state - receptors are more specific cause not impacted by chronic disease states - & 2nd stage iron def
–> … serum Fe decreases, TIBC increases [more free binding sites as not much iron bound to transferrin]
Sensitivity
- More sensitive than hemoglobin; can detect 2nd stage of iron deficiency
Specificity
- Distinguish between iron deficiency and folate and B12 deficiencies
- Chronic disease status also result in low transferrin saturation
- TIBC decreases due to inflammation, chronic infection and malignancy, which can mask iron deficiency
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Sensitivity
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Specificity
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- Measures protoprophyrin, the immediate heme precursor (for Hb production)
- If there isn’t enough iron, FEP increases
Sens
- FEP increases when there is insufficient Fe for Hb production, often before anemia starts
- Can detect Fe deficiency erythropoiesis
Spec
- FEP increases with lead poisoning [sits in protopro molecule & not allow iron to sit in molecule to be converted to Hb], infection & chronic inflammation
- FEP remains within the normal range in thalassemia (genetic disorder) (another cause of hypochromic microcytic anemia)
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Sensitivity -
Specificity -
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* can reflect 1st stage of deficiency - ONLY one that can do this *
- SLIDE 29 - chart summary - review *
- Ferritin is main form of Fe storage
(mainly in the liver, spleen, skeletal muscle and bone marrow) (only a small amount in the blood) - Serum ferritin levels then to reflect Fe stores
- A low value in an anemic individual identifies iron deficiency anemia (the only measure that can reflect deficient, excess or normal iron status
Sens - good
Spec - the big problem
- Ferritin is a positive acute phase reactant protein THEREFORE can be impacted by inflammation - need to ensure no inflammation before understanding values
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- Most clinicians stat with anemia - Hemoglobin
- If iron deficiency is suspected, may also use serum ferritin
- May skip serum ferritin if other assessment methods point to iron
- Note: decrease Hb with decrease ferritin is unequivocal evidence of iron deficiency, but decrease Hb with normal ferritin does not rule out iron deficiency - just means other reasons for low Hb
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What does Shirley have?
How else might we find out if ferritin values were not available?
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- Using multiple indices simultaneously provides a more accurate measure of Fe status
- Dietary info and other clinical information can also provide important info
Shirley
- We checked her ferritin levels and they are 10ug/L (Normal is 18-300ug/L)
- Very low iron stores (low serum ferritin) –> confirm her iron-deficiency anemia
- Serum Iron, Total Iron Binding Capacity,
Transferrin Saturation & Free Erythrocyte
Protoporphyrin are also useful indicators of
iron deficiency anemia
WHY Jeff has MACROcytic anemia?
Folic Acid (Folate)
Red blood cell (RBC) folate
–> Static test - reflects:
( )
( )
–> : folate stores
Sens
- Reflects folate status at the time the RBC was synthesized b/c only young cells take up folate (the avg lifespan of a RBC is 120 days)
(RBC folate tends to decline after several months of folate deficiency)
Spec
- Not specific for folate deficiency - low values also occur in B12 deficiency
( Vit B12 deficiency -> affect intracellular folate metabolism –> reduced RBC folate levels )
Plasma homocysteine (tHCY)
–> Functional test
Specificity
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VISUAL - slide 38 (Folate, B12 and homocysteine metabolism)
Neutrophil lobe count
–> Functional test
- ______ is the earlier hematological sign of folate deficiency
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Specificity
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sens
- Less sensitive to short term fluctuations than serum folate
spec
- Not specific for folate deficiency - high tHCY also occurs in B12 deficiency - can only suggest problem with folate metabolism
- Hypersegmentation
- Abnormal if avg number of lobes is > 3.5 or if >/= 5% of cells have five or more lobes
- An increase in the size of RBCs (MCV) generally follows
Sens
- No relationship btw the severity of deficiency and degree of hypersegmentation
Spec
- Does not distinguish between folate and B12 deficiencies
(Defects caused at the level of bone-marrow forming cells and DNA replication)
- May occur in other conditions as well (ie. uremia, iron deficiency)
Serum Folate
–> Static test - reflects…
Sensitivity
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Specificity
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–> … folate transport
Sensitivity
- Very sensitive to recent changes in dietary intake
- Can’t distinguish btw recent decrease in intake and chronic deficiency [Recent folic acid administration or dietary folate intake could result in normal or elevated serum folate values, & possibly mask an underlying folate deficiency (false negative result)]
Spec
- High serum folate values are seen in patients with hemolysis of red blood cells or kidney disease
- Low serum folate values are seen in patients with excessive alcohol consumption, smoking, pregnancy, and oral contraceptive use
- If serum folate and RBC folate are both low, this strongly suggests folate deficiency
- Folate deficiency is rare in Canada - due to fortification law
VITAMIN B12
Vitamin B12 Deficiency
- Much more common than ____
( Anemia caused by B12 deficiency can be masked…)
*can hit an irreversible point - not good *
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Serum B12
–> Static test
- Used for screening of Vit B12 deficiency
–> Measures…
- about ____ of B12 is attached to…
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Specificity
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- ___ folate deficiency___
( … by folate supplementation) - Myelination of neurons
- Dementia
- Nerve problems
- Will not be solved with folate supplementation
–> … total serum B12 * not the most sens/spec
- About 20% of B12 in serum is attached to the transport protein, transcobalamin II (this is the only transport protein that can deliver B12 to cells - cell membranes have receptors for it)
- Remaining (80%) B12 serum is attached to other proteins (non-active) *therefore you are measuring the active and non-active levels
Sens
- Low sensitivity - no significant change in serum B12 until saturation of transcobalamin II has already declined (usually deplete the 80% non active 1st then the active) - its too late by the time it can sense B12 deficiency
Spec
- Serum B12 levels are affected by levels of serum binding proteins - disease states can alter the levels of these binding proteins (ie. liver disease, genetic diseases) - low spec as there are factors to say yes there is deficiency when may not be or vice versa
Holotranscobalamin II
–> Static test
–> “holo” means a a transport protein together with the associated group it is carrying (measuring the active form)
- Measurement of holotrans II reflects…
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Specificity
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- … reflects the amount of transcobalamin II in the blood that is carrying B12
Sens
- Early, sensitive measure of low B12
- Transcobalamin has a short half-life (1.5 hours) - concentrations fall quickly if B12 absorption drops
- Much more sensitive than serum B12
Spec - more specific than plasma homocysteine
- Difficult assay –> not commonly used
- Homocysteine with (increase (accumulate) with low folate and low B12
Schilling test
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Procedure
1
2
- After each step…
[If B12 excretion increases with intrinsic factor =]
Jeff:
[Vitamin B12 deficiency - is causing his macrocytic anemia]
–> Can be used to determine the cause of B12 deficiency
- Also called Vit B12 absorption test
- Rarely done
1 a radio-isotope of Vit B12 is given alone
2 A radio-isotops of Vit B12 is given WITH intrinsic factor
- … the amounts of the radio-isotope in the urine is collected, and the differences between step 1 and 2 are compared
= lack of intrinsic factor is causing malabsorption and low B12 status
- NUTRIENTS OF CONCERN IN THE DEVELOPING WORLD - read this slide deck *
