Microcytic Anemia

Iron
o Iron Deficiency (MC)
Labs
Decreased serum ferritin, iron, and % saturation
Increased TIBC, RDW, FEP
Causes
Infants/children= diet
Men under 50= PUD
Women under 50= menorrhagia/pregnancy
Over 50= GI bleed/cancer
Malnutrition, malabsorption (celiacs), gastectomy, and
hookworms
o Chronic disease- usually normocytic
Labs
Increased serum ferritin
Decreased serum iron, % saturation, and TIBC
Usually mild (Hb 10-11)
May be hypochromic/microcytic if TB or active RA present
Causes
Chronic inflammatory states
o Bacterial infections- osteomyelitis, lung abscess,
endocarditis
o Autoimmune- RA, IBD
o Cancer
Hepcidin- decreases iron absorption/release; produced in liver
TNF, IL-1, interferon- suppress release of EPO/bone marrow
response
Protoporphyrin
o Sideroblastic
Labs
Increased serum iron, ferritin, % saturation; Sideroblasts,
hypochromic RBCs
Decreased TIBC- defect in iron incorporation into heme in
mitochondria
Prussian blue to show ring sideroblast= of nucleus
Causes
Alcohol excess MC
Pyridoxine (B6) deficiency (malnutrition, INH), Myelodysplastic
syndromes
o Lead poisoning
Children more susceptible
Blood-brain-barrier not well developed= CNS threat
Increased iron absorption= increased lead absorption
Crawling, hand-mouth behavior increases risk of exposure
Sources- paint, mining, car parts, pottery, moonshine, batteries,
ammunition

Inhibits
ALAD= no ALA to porphobilinogen (porphryin precursor)
Ferrochelatase= no production of heme from porphyrin 9
Pyrimidine-5-nucleotidase: clumping of RNA basophilic stiplling
o Treat by removing source + chelation therapy
Symptoms
Children
o encephalopathy (increased ALA= demyelination)
o Growth retardation, and abdominal colic, wrist/foot drop
Adults
o Neuropathy, proximal tubule damage (proximal RTA)
Labs
XR- Pb chips on abdomen, lead lines- Pb deposits in epiphysis

Globin
o Alpha thalassemia
Labs
Increased RBC count; presence of target cells
Reduced MCV and MCH; mild anemia
Electrophoresis- no change in % of Hb A, A2, or F
Causes
Autosomal recessive; deletion of gene on chromosome 16
o Trans deletion= Black people MC
o Cis deletion= Asians MC
HbH disease- more common in Asians due to cis configuration
3 deletions= moderately severe hemolytic anemia
RBCs sensitive to oxidative stress; sulfur drugs bad
Hb Barts (Y4)- more common in Asians
Total absence of alpha synthesis; avid binding to O2
Severe intrauterine hypoxia, CHF, hydrops fetalis, death in utero
o Beta thalassemia
Labs
Minor
o HbA decreased
o HbA2, HbF increased; target cells
Major- No HbA; increased HbF; target cells
Causes
Autosomal recessive disorder; MC in blacks, Italians, Greeks,
Africa, SE Asia
Minor
o Heterozygotes; 1 defective gene= mild microcytic anemia
Major- Severe transfusion-dependent anemia; microcytic
hypochromic
o Homozygous; both genes= no beta globin= no HbA
o Unpaired alpha globin chains are insoluble= toxic
inclusions
ineffective erythropoiesis
o Hemosiderosis

o Hereditary persistence of HbF

No deleterious effects; seen using Kleihauer-betke stain ( appear
darker)
o Carbon monoxide poisoning
Higher affinity for Hg; forms carbxyhemoglobin
Cherry red skin color, seen in smokers= 2* polycythemia; treat w/ O2
o Methemoglobinemia
Oxidation of iron to ferric (Fe3) state
Over 50-60% is fatal
Appear cyanotic, high PaO2, chocolate brown skin
Diagnose w/ methemoglobin assay; Treat w/ methylene blue
o Erythroid hyperplasia
Expansion of marrow cavity from accelerated erythropoiesis
Seen in severe hemolysis- beta thalassemia major, sickle cell
Hair on end XR appearance; frontal bossing, pronounced maxilla
Macrocytic anemia
Drugs that interfere w/ DNA synthesis
o 5-FU, TMP, MTX
Megaloblastic anemia
o Deficiency in B12/folate= deficient in DNA synthesis
o Labs
Bone marrow
Large abnormal cells w/ immature chromatin (not condensed)
Peripheral blood
Macrocytic RBCs, hypersegmentation PMNs, Pancytopenia
o *hypersegmentation is earliest change seen (>5 lobes)
o B12 (cobalamin)
Usually secondary due to malabsorption
Found only in food of animal origin
Body has large storage to last 3-4 YEARS
Macrocytic anemia + neurologic signs
Relatively common in >65; thought 2* to hypochlorhydria
Methylfolate trap (restricts folate supply)
o Absorption mechanism / causes of deficiency
Pepsinogen is catalyzed to pepsin using HCL
Hypochlorhydria
Haptocorrin (salivary glands) binds to B12 after pepsin releases B12
Sjogrens syndrome- salivary gland disorder
IF (parietal cells) binds to B12 after trypsin (pancreas) cleaves
heptocorrin
Pernicious anemia= lacks IF
Chronic pancreatitis= cant cleave haptocorrin from complex
IF-B12 absorbed in terminal ileum
Bacterial overgrowth; Fish tape worm (D. latum); Crohns (term.
ileum ileal)
B12 binds to transcobalamin II and transported to BM, dividing cells
Transcobalamin II deficiency

o Mechanism for neurological effects of B12 deficiency

Increased levels of methylmalonyl CoA (MMA)
No conversion to succinyl CoA due to lack of B12
Damages due to demyelination and axonal degreneration/ neuronal
death
o Folic acid
Secondary to inadequate dietary intake
Present in most foods; high in liver, nuts, spinach, greens
MC in alcoholics, elderly; limited storage of 3-4 MONTHS
Only macrocytic anemia
o Absorption mechanism/ causes of deficiency
Consumed in green vegetables/meat products
Decreased intake MCC
Polyglutamate converted to monoglutamate by intestinal conjugase in
jejunum
Drug inhibition of intestinal conjunase (phenytoin)
Monoglutamate absorbed in jejunum; converted to
methyltetrahydrofolate
Malabsorption- celiac disease
Increased utitilization- pregnancy, lactation, disseminated cancer
Decreased absorption- EtOH, phenytoin, oral contraceptives
Used in DNA synthesis
Drug inhibition
o 5flurouracil (thymidylate synthase)
o MTX TMP ( dihydrofolate reductase)
o Labs
Increased serum homocysteine
Macro-ovalocytes; hypersegmentation of neutrophils
o Symptoms/signs
Glossitis
Diarrhea
B12
Peripheral neuropathy
Subacute combined degeneration (posterior column, pyramidal
tracts)
Dementia, psychiatric, or visual disturbances
o Schilling test
If urine is positive
Radioactive cobalamin
= B12 deficiency
Radioactive cobalamin + IF
= pernicious anemia
Radioactive cobalamin + enzymes
= Pancreatitis
Radioactive cobalamin + antibiotics
= pernicious anemia
No test needed if megaloblastic anemia, decreased serum cobalamin,
IF
Alcohol induced macrocytosis
o May or may not have anemia
o No hypersegmented PMNS

o May develop leukopenia and/ or thrombocytopenia