Anemias of diminished erythropoiesis

1. General anemia overview (high-yield)

Anemia = decreased RBC mass, typically reflected by ↓Hb and/or ↓Hct (and often ↓RBC count).

Main consequence: reduced O₂-carrying capacity → fatigue, pallor, dyspnea.

Compensation: bone marrow hyperplasia; in severe/chronic states, extramedullary hematopoiesis (spleen/liver).

Two common ways to classify:

• Morphology (MCV-based): microcytic / normocytic / macrocytic
• Pathogenesis: ↓production vs ↑destruction vs blood loss

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2. Anemias of diminished erythropoiesis (↓production)

2.1 Iron deficiency anemia (IDA)

Most common cause of anemia.

Iron distribution (concept):

• Majority in hemoglobin; remainder in myoglobin/enzymes and storage pool (ferritin/hemosiderin).
• Serum ferritin reflects body iron stores.

Absorption & loss

• Absorbed in duodenum (heme iron from meat; non-heme from vegetables).
• Lost via shedding of mucosal/epithelial cells (unregulated compared with regulated absorption).

Pathogenesis = negative iron balance

a) Chronic blood loss (GI ulcers/cancers; gynecologic bleeding)

b) Low intake / poor bioavailability

c) Malabsorption (intestinal mucosal disease, post-gastrectomy)

d) Increased demand (pregnancy, infancy)

Progression

1. Depleted stores → ↓ferritin

2. ↓serum iron + ↑TIBC

3. Impaired Hb synthesis → microcytic hypochromic anemia + functional impairment

Morphology

• Microcytosis (↓MCV)
• Hypochromia (↓MCHC)

Clinical

• Often mild/insidious; weakness, pallor
• Long-standing: koilonychia (spoon nails), pica

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2.2 Anemia of chronic disease / inflammation

Common in hospitalized patients.

Associated with

• Chronic infections (osteomyelitis, endocarditis, lung abscess)
• Chronic immune disorders (e.g., RA)
• Neoplasms (e.g., lung/breast cancer, lymphoma)

Pathogenesis (core idea): hepcidin-mediated iron restriction

• Inflammatory cytokines (esp. IL-6) → ↑hepcidin (liver)
• Hepcidin ↓ferroportin → iron trapped in macrophages / decreased delivery to erythroid precursors
• Pattern: low serum iron, increased storage, high ferritin, reduced TIBC (not true iron deficiency)
• Also ↓EPO response → ↓RBC production

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2.3 Megaloblastic anemia (folate and/or vitamin B12 deficiency)

Both are required for DNA synthesis (thymidine).

Pathogenesis: nuclear–cytoplasmic asynchrony

• DNA synthesis impaired → delayed nuclear maturation and cell division
• RNA/cytoplasm proceeds relatively normally → cellular gigantism
• Ineffective hematopoiesis → intramedullary apoptosis → can progress to pancytopenia

Morphology

• Hypercellular marrow with megaloblasts
• Giant metamyelocytes; abnormal large megakaryocytes
• Peripheral blood: macro-ovalocytes and hypersegmented neutrophils
• High MCV, normal MCHC

Folate deficiency

• Causes: poor diet, increased demand (pregnancy, hemolysis), malabsorption (celiac, tropical sprue)
• Folate in foods but destroyed by prolonged cooking.

Vitamin B12 deficiency (pernicious anemia)

• Causes: strict vegetarian diet, long-standing malabsorption, post-gastrectomy
• Intrinsic factor (IF) from parietal cells binds B12; complex absorbed in ileum
• Pernicious anemia: autoimmune against parietal cells/IF → gastric atrophy → IF deficiency
• Important: folate can correct anemia but does not correct neurologic deficits
• Clinical: posterior/lateral column demyelination (paresthesias), ↑risk of gastric carcinoma

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2.4 Aplastic anemia

Stem cell suppression → bone marrow failure → pancytopenia.

Causes

• Idiopathic (common)
• Viral (hepatitis, EBV, CMV, parvovirus B19, HIV) with immune mechanisms
• Myelotoxic agents (drugs, chemicals, chemotherapy)

Morphology

• Hypocellular marrow with fat replacing hematopoietic tissue

Clinical

• Anemia symptoms
• Thrombocytopenia → petechiae/bleeding
• Neutropenia → recurrent bacterial infections

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2.5 Myelophthisic anemia

Anemia due to marrow being replaced/infiltrated by

• tumor cells (metastatic breast/lung/prostate, etc.)
• fibrotic lesions (myelofibrosis)

Morphology

• Teardrop RBCs (dacrocytes)
• Leukoerythroblastic picture (nucleated RBCs + immature WBCs)

💡 High-yield: ↓production anemias include IDA (microcytic), ACD/hepcidin (iron-restricted), megaloblastic (macro-ovalocytes + hypersegmented neutrophils), aplastic (hypocellular marrow + pancytopenia), myelophthisic (tear drops + leukoerythroblastosis).