97 - Iron Deficiency and Hypoproliferative Anaemias Flashcards
Hypoproliferative anaemias are anaemias associated with __ and __ red cells and inappropriately __ reticulocyte response (retics index < 2-2.5)
Hypoproliferative anaemias are anaemias associated with normochromic and normocytic red cells and inappropriately low reticulocyte response (retics index < 2-2.5)
Causes of hypoproliferative anaemias (6)
- Early IDA (before HCMC anaemia)
- Inflammation (acute or chronic)
- Renal disease
- Hypometabolic states - protein malnutrition
- Endocrine deficiencies
- Marrow damage
What are the 3 stages of iron deficiency
1. Negative iron balance
- Demand/losses of iron exceeds absorption
(blood loss >10-20mL RBC/day)
2. Iron deficient erythropoiesis
- Depletion of marrow iron stores (ferritin < 15 mcg/L)
- Hb sysnthesis impaired - microcytosis, hypochromic reticulocytes
3. Iron deficiency anaemia
- drop in Hb to anaemic levels
- At Hb 10-13, bone marrow hypoproliferative
- At Hb 7-8, hypochromia and microcytosis, target cells and poikilocytes (cigar/pencil shaped), erythroid hyperplasia
In iron deficient erythropoiesis,
Hb synthesis is __ and Hb levels gradually __, with increasing __ and __
Serum ferritin drops below __ and transferrin saturation falls to __
In iron deficient erythropoiesis,
Hb synthesis is impaired and Hb levels gradually drops, with increasing TIBC and RBC protoporphyrin.
Serum ferritin drops below 15mcg/L and transferrin saturation falls to 1-15%
Common histology of severe anaemia
- RBC colour and size
- RBC morphology
- Erythroid cell line in marrow
Hypochromic, microcytic anaemia
Target cells
Poikilocytes (cigar or pencil shaped)
Erythroid hyperplasia
3 groups of causes of iron deficiency
1. Increased demand
- Rapid growth - infancy, adolescence
- Pregnancy
- Erythropoietin therapy
2. Increased loss
- Chronic blood loss
- Menstruation
- Acute blood loss
- Blood donation
3. Reduced absorption
- Inadequate diet
- Malabsorption - sprue, Crohn
- Surgical procedure - gastrectomy, bariatric surgery
- Acute or chronic inflammation
Average RBC lifespan is __, with __% of RBCs replaced daily.
Each mL of RBC contains __ of elemental iron
Assumption of adult with RBC mass of 2L, daily iron requirement __ (1% of 2L = 20mL = 20mg)
Once RBC is recognised as senescent by ____, RBC will undergo __, Hb broken down, globins and proteins return to amino acid pool, while iron is presented to __ via iron export channel __
Average RBC lifespan is 120 days, with 0.8-1% of RBCs replaced daily.
Each mL of RBC contains 1mg of elemental iron
Assumption of adult with RBC mass of 2L, daily iron requirement 20mg/day (1% of 2L = 20mL = 20mg)
Once RBC is recognised as senescent by reticuloendothelial system, RBC will undergo phagocytosis, Hb broken down, globins and proteins return to amino acid pool, while iron is presented to transferrin via iron export channel ferroportin
Iron metabolism
Iron storage
Physiological iron loss/excretion
- Sources of iron
A. dietary absorption in duodenum (10% absorbed)
- Brush border of intestimal cells, basolateral membrane through active transport
B. released from iron stores - Transferrin - transports iron in plasma
(Transferrin saturation = ferritin / TIBC) - Iron-transferrin complex reaches marrow erythroid cells -> free iron binds to apoferritin to form ferritin
(Also occurs in liver for haem-containing enzyme synthesis or for storage) - Iron storage
- 80% in haemoglobin
- 20% in myoglobin and iron-containing enzymes
- Storage sites: liver, spleen, bone marrow, skeletal muscles - Physiological iron loss/excretion
- Blood loss: GI tract, menstruation
- Epithelial cell shedding: skin, gut, genitourinary tract
- Pregnancy
Daily iron requirement in men and women
Male: 10mg/day (of which 1mg elemental iron absorbed)
Female: 30mg/day (of which 1.4-3mg absorbed, higher demand due to menstruation and childbearing age)
Factors influencing iron absorption
- Enhances absorption
- Stomach acidity
- Vitamin C
- Proteins - Inhibits absorption
- Phytic acid (cereals)
- Oxalic acid (leafy greens)
- Minerals: calcium, copper, lead, phosphate
- Medications: PPI, tetracycline
Iron deficiency in male or postmenopausal womenm the cardinal rule is to rule out __
Gastrointestinal blood loss
Clinical presentation of iron deficiency (5)
- Fatigue
- Pallor
- Reduced exercise capacity/effort tolerance
- Cheilosis (fissues at corners of mouth)
- Koilonychia (spooning of fingernails)
Laboratory Iron Studies
1. Serum iron reflects iron bound to __
Normal range: __
- TIBC is a indirect measure of __.
Normal range: __ - Ferritin reflects __ in the cells of __ system
Normal range: __ (male) or __ (female)
Iron deficiency: __
Ferritin may be falsely elevated in __ - Transferrin saturation: (serum iron x100) / TIBC
Normal range: __
Iron deficiency: __
Iron excess: __
- Serum iron reflects iron bound to transferrin
Normal range: 50-150 ug/dL - TIBC is a indirect measure of transferrin.
Normal range: 300-360 ug/dL - Ferritin reflects iron stores in the cells of RE system
Normal range: >100 (male) or >30 ug/L (female)
Iron deficiency: < 15 ug/L
Ferritin may be falsely elevated in _acute inflammation__ - Transferrin saturation: (serum iron x100) / TIBC
Normal range: 25-50%
Iron deficiency: < 20%
Iron excess: > 50%
Evaluation of bone marrow for iron deficiency has largely superseded by serum ferritin measurement.
Marrow smear stained for iron: __ (developing erythroblasts) presents in ____ (percentage), have visible ferritin granules in cytoplasm. (representing iron __ of that needed for haemoglobin synthesis)
In ____, ____ occurs with accumulation of iron in mitochondria in a necklace fashion around nucleus of erythroblast, referred to as __
Marrow smear stained for iron: sideroblast (developing erythroblasts) presents in 20-40%, have visible ferritin granules in cytoplasm. (representing iron in excess of that needed for haemoglobin synthesis)
In myelodysplastic syndromes, mitochondrial dysfunction occurs with accumulation of iron in mitochondria in a necklace fashion around nucleus of erythroblast, referred to as ring sideroblasts.
Protoporphyrin is intermediate in pathway of __.
Protoporphyrin accumulates in RBC in __ (condition), reflecting __ iron supply to erythroid precursors to support haemoblogin synthesis.
Protoporphyrin also accumulates in RBC in __ (condition) where haem synthesis pathway enzymes are __
Normal values: __
Iron deficiency: __
Protoporphyrin is intermediate in pathway of haem synthesis.
Protoporphyrin accumulates in RBC in _iron deficiency, reflecting inadequate iron supply to erythroid precursors to support haemoblogin synthesis.
Protoporphyrin also accumulates in RBC in lead poisoning where haem synthesis pathway enzymes are inhibited
Normal values: < 30 ug/dL
Iron deficiency: > 100 ug/dL
