Pathophysiology
1) cause – lack of intrinsic factor in gastric secretions 2) adult form – deficiency of intrinsic factor owing to gastric atrophy or autoimmune disease 3) congenital form– deficiency of intrinsic factor with normal gastric lining
Signs and Symptoms
1) classic symptom triad – weakness, sore tongue, paresthesias (occurring initially in tips of toes) 2) typically has insidious onset 3) GI disturbances (diarrhea, constipation, pain) 4) skin hyperpigmentation/velvety smooth skin 5) weight loss 6) hepatomegaly/moderate splenomegaly 7) icterus from hemolysis 8) fever 9) psychiatric disturbances (delusions, “megaloblastic madness”)
Characteristic Test Findings
Laboratory – 1) macrocytic normochromic anemia (7-9 mg/dL 2) increased gastrin levels owing to lack of acid production 3) thrombocytopenia/leukopenia 4) prolonged bleeding time 5) increases serum iron 6) increased MCV
Histology/Gross Pathology
1) gastric mucosal atrophy 2) intestinal metaplasia 3) G cell hyperplasia in antrum 4) myelin degeneration if dorsal and lateral spinal tracts 5) degeneration of dorsal root ganglion, celiac ganglion, and Auerbach’s and Meissner’s plexuses
Associated Conditions
1) most serious long-term complication is carcinoma of stomach (stomach cancer) 2) thyroid disease (both hypo/hyperthyroidism 3) Addison’s disease 4) vitiligo 5) carcinoid 6) colorectal cancer 7) increased incidence with – gastric bypass, gastric acid surgery
Biochemistry
1) no hydrogen ion secretion (99%) 2) autoantibodies to gastric parietal cells (85%), intrinsic factor (lack causes impaired vitamin B12 absorption) and thyroid tissue 3) decreased suppressor T cells and increased cytotoxic killer cell activity
Inheritance/Epidemiology
1) most common in Scandanavian, English, and Irish ancestry 2) occurs in 9-17/100,000 population 3) female to male, 1.4:1.0 4) congenital form is autosomal recessive 5) adult form is influenced by some genetic factors (incidence is increased 25 times in family members) 6) incidence increases with age and rarely occurs before age 30 years
Treatment
1) injections of 100 micrograms B12 IM for 1 week; then at increasing intervals as needed 2) adequate vitamin B12 levels are being achieved when the reticulocyte count begins to increase 3) maintenance therapy is monthly injections for life
Tips for USMLE
1) anemia does not correspond to severity of neurologic deficits 2) another name for vitamin B12 is cobalamin 3) if the question mentions tongue soreness as the initial symptom (beefy red tongue with a smooth glaze to it), think pernicious anemia 4) if Castle’s factor is mentioned, think pernicous anemia
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