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Iron Deficiency Anaemia (IDA) Megaloblastic Anaemia

Iron Storage & Transport Causes

Transferrin Vitamin B12, Folate Deficiency
Iron + Apotransferrin = Transferrin Results in ↑ homocysteine & ↓ DNA synthesis
Binds to Iron, Protect Tissues from Iron Toxi city
TfRs fou nd at Hepatocytes, Immature RBC, Rapidly dividing cells Megaloblasts
Ferritin Enlarged erythroblasts with delayed nuclear maturation due to defective DNA
Intracellular iron storage synthesis
Iron bound → Ferric (Fe3+) Characteristics
Haemosiderin Size ↑ compared to Normoblasts
Insoluble protein ↑ Immature Nuclei
Predominantly in macrophages ↑ Striking Basophilic cytoplasm
Finely reticulated nuclear chromatin
Iron Absorption Nuclear-Cytoplasmic asynchrony
Better absorbed in Ferrous form (Fe2+)
Absorption favoured by Acid, Reducing Agents Morphology Other Morphology
Requirements ↑ in Immature nuclear (cytoplasmic Hypercellular Bone Marrow
Growth periods development normal) Macrocytes
Loss of blood (Nucleo : cyto ratio asynchrony) (Large red cells, Hyperchromic)
Menstruation Giant metamyelocytes (Enlarged Abnormally large Bizarre multilobed
Pregnancy granulocyte precursors) nuclei in megakaryocytes
Heme iron is absorbed better Mature neutrophil (show Large, misshapen Platelets
Site of absorption – Duodenum, Jejunum Hyperpigmentation/
Heme receptor – Absorb Heme-boun d iron Hypersegmented)
DMT-1 (Divalent Metal Transporter-1) – Absorb Non-Heme-bound iron (show ↑ Nuclear Lobes )
Stored as Ferritin

Symptoms Skin, Nail, Epithelial changes

Lethargy Pale skin color (pallor)
Dizziness Koilonychia
Irritability Angular stomatitis
Dyspnoea Glossitis
↓ Appetite Esophageal & Pharyngeal webs
Megaloblastic anaemia
Pica (Crave for non-food )

Signs & Symptoms

Glossitis
Angular stomatitis
Mild Jaundice
Lethargic
Anaemia
Breathlessness
Koilonychia Angular stomatitis Visual disturbance

Diagnostic Feature
FBC
Hb ↓
MCV > 96fl
Erythrocyte count ↓ - Anaemia
Blood film examination
Macrocytosis
Neutrophil hyperpigmentation
Serum ferritin
Serum B12
Glossitis Red cell Folate

Lab Investigations Investigation Underlying Causes General Treatment

FBP Rectal examination Blood transfusion
Serum Iron Occult blood test (Not indicated in Chronic Anaemia)(Dangerous in elderly)
Serum Ferritin Stool for ova & cyst Large doses of Folic Acid alone
(used only when Serum Vitamin B12 is normal)
TIBC (Total Iron Binding Capacity) Urine examination
Bone Marrow Examination CXR
Pathogenesis
ECG
Serum Urea & Electrolyte

Treatment
Determine cause of iron deficiency/ Source of bleeding
Iron replacement therapy
Ferrous sulfate
Ferrous fumarate
Ferrous succinate
Ferrous gluconate
Parenteral Iron
Iron dextran
Iron sorbitol-citrate
Blood transfusion – if de compe nsated anaemia
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Folate Vitamin B12

Sources Absorption
Green vegetables (eg. Spinach, Broccoli) Cobalamin
Fruits Found in Animal Food origin (Vegetarians – Deficiency)
Yeast extract Stores in Liver 2-3mg for 2-3 years
Wholemeal bread Active Transport Absorption in Ileum
Offal (eg. Liver, Kidney) Bind to IF (secreted by Parietal cell) → IF-B12 comple x
Transported by Transcobalamin (TC) & Haptocorrin (Hapt) in blood
Functions
Production of RBCs Functions
Synthesis of DNA CNS Maintenance (include Brain, Spinal cord)
Works with B12 and Vitamin C to help digest & utilize proteins RBC Formation
DNA Synthesis (Metabolism)
Dietary Folate
Minimum requirement – 100 ug B12 Deficiency
Predominantly in polyglutamate form Malnutrition
80-90% destroyed by 10-15 minutes cooking ↓ IF
Absorption – Proximal 1/3 of small intestine (Duodenum, Jejunu m) ↓ Transcobalamin
↓ IF – receptor
Excretion Malabsorption syndrome
Urine Gastrectomy
Skin Old age – Gastric Atrophy & Achlorhydria - ↓ Acid & Pepsin produced
Sweat Autoimmune – Pernicious anaemia

Folate Deficiency Pernicious Anaemia

Autoimmune action on Parietal cell & IF → ↓B12 absorption
3 types of Autoantibody
Parietal canalicular A/B → Parietal Cell
Blocking A/B → Block B12 binding to IF
Binding A/B → Preveng IF-B12 bind to IF receptor
Associated with
Hashimoto Thytoiditis
Addison disease

Clinical
Pallor
Fatigue
Causes of Folate Deficiency Severe dyspnoea & Congestive Heart Failure
Nutrition Angular stomatitis & Glossitis
Poor intake – Old age, Social conditions, Starvation, Alcoholism Symmetrical numbness, Tingling in sensation in Feet & Hand
Poor intake (due to anorexia) – Cancer, GIT disease (eg. Celiac disease) Loss in positioning
Excess Utilization Serum Bilirubin ↑
Physiological – Pregnancy, Lactation, Prematurity
Pathological – Haemolysis, Malignant disease with ↑ cell turnover, Dialysis Subacute combine d degeneration Spinal Cor d
Antifolate drugs ↓ B12 → ↑Homocysteine → Defect myelinaƟon → Neuropathy
Anticonvulstants (eg. Phenytoin) Affect mainly Posterior & Lateral Column
Methotrexate Mainly Lower Limb affected
Pyrimethamine
Trimethoprim Diagnostic Feature
Malabsorption ↓ Serum Vitamin B12
Small bowel disease Normal/ ↑ Folate
Serum A/b to IF ↑
Clinical Myeloblastic anaemia
Anaemic symptoms Anemic signs Leukopenia with hyperpigmentation/ Hypersegmented granulocyte
Fatigue Pallor Dramatic response to B12
Headaches Tachycardia
↑ Homocysteine, Methymalonic a.
Faintness Systolic flow murmur
Weakness Cardiac failure
Investigation Management
Breathlessness
Schiling Test Cyanocobalamin/ Hydroxocobalamin
Angina
(Radioactive oral B12)
Intermittent claudication
(Non-radioa ctive IV B12)
Palpitations
If Normal, >10% oral dose excreted
Symptoms of underlying cause (eg. Sore tongue, Cheilosis, Glossitis)
If Abnormal, indicate
↓ Growth velocity (children)
Pernicious Anaemia/ Gastrectomy
No neuropathy
(will produced back normal value if IF
capsulated is added)
Investigation Management
If still Abnormal, likely
MCV > 96 fl Folic Acid Bacterial growth
Peripheral Blood Film Treat underlying cause (will produced normal if IF capsule +
(Oval macrocytes, Hypersegmented Prophylactic Folic Acid (planning a antibiotic)
polymorphs >6 nuclear lobes) pregnancy)
Bone Marrow examination Folate & B12 Deficiency in Clinical Finding
Blood measureme nt (Serum & Red Cell Folate B12
Folate) (radioisotope dilution/ Neural symptom Absent Present
immunological method s)
Serum Vit B12 - +
(distinguish Folate/ B12 deficient)
Serum Folate + -
Normal Serum Folate – 4-8 ug/L
Serum Homocysteine + +
Normal Tissue Folate – 160-640 ug/L
Serum Methylmalonic - +
Small bowel biopsy – occult GIT disease