Guest guest Posted September 18, 2004 Report Share Posted September 18, 2004 http://www.merck.com/mrkshared/mmanual/section1/chapter3/3j.jsp Thiamine Deficiency And Dependency The coenzyme thiamine pyrophosphate, the active form of thiamine (vitamin B1), participates in carbohydrate metabolism through decarboxylation of alpha-keto acids. Thiamine also acts as coenzyme to the apoenzyme transketolase in the pentose monophosphate pathway for glucose. Deficiency causes beriberi with peripheral neurologic, cerebral, cardiovascular, and GI manifestations. Etiology Primary thiamine deficiency is caused by inadequate intake of thiamine, particularly in people subsisting on highly polished rice. Milling removes the husk, which contains most of the thiamine, but boiling before husking disperses the vitamin throughout the grain, thus preventing its loss. Secondary thiamine deficiency is caused by increased requirement, as in hyperthyroidism, pregnancy, lactation, and fever; impaired absorption, as in prolonged diarrheas; and impaired utilization, as in severe liver disease. A combination of decreased intake, impaired absorption and utilization, increased requirements, and possibly an apoenzyme defect occurs in alcoholism. Frequent, long-term, or highly concentrated dextrose infusions, coupled with low thiamine intake, may precipitate thiamine deficiency. Pathology The most advanced neural changes occur in the peripheral nerves, particularly of the legs. The distal segments are characteristically affected earliest and most severely. Degeneration of the medullary sheath can occur in all tracts of the spinal cord, especially in the posterior columns and in the anterior and posterior nerve roots. Changes also occur in the anterior horn and posterior ganglion cells. Lesions of hemorrhagic polioencephalitis occur in the brain when deficiency is severe. The heart is dilated and enlarged; muscle fibers are swollen, fragmented, and vacuolized, with interstitial spaces dilated by fluid. Vasodilation occurs and can result in some edema before frank high-output heart failure occurs. Symptoms and Signs Early deficiency produces fatigue, irritation, poor memory, sleep disturbances, precordial pain, anorexia, abdominal discomfort, and constipation. The syndrome of peripheral neurologic changes due to thiamine deficiency is called dry beriberi. These changes are bilateral and symmetric, involving predominantly the lower extremities, and begin with paresthesias of the toes, burning of the feet (particularly severe at night), muscle cramps in the calves, and pains in the legs. Calf muscle tenderness, difficulty in rising from a squatting position, a decrease in the vibratory sensation in the toes, and plantar dysesthesia are early signs. A diagnosis of mild peripheral neuropathy can be made when ankle jerks are absent. Continued deficiency causes loss of knee jerk, loss of vibratory and position sensation in the toes, atrophy of the calf and thigh muscles, and finally footdrop and toedrop. The arms may be affected after leg signs are well established. Cerebral beriberi (Wernicke-Korsakoff syndrome) results from severe acute deficiency superimposed on chronic deficiency (see Amnesias in Ch. 169). Mental confusion, aphonia, and confabulation constitute the early stage, called Korsakoff's syndrome. Cerebral blood flow is markedly reduced and vascular resistance increased. Wernicke's encephalopathy consists of nystagmus, total ophthalmoplegia, coma, and, if untreated, death. Cardiovascular (wet) beriberi (Shoshin beriberi) occurs in thiamine deficiency when myocardial disease is prominent. This causes a high cardiac output with vasodilation and warm extremities. Before heart failure occurs, tachycardia, a wide pulse pressure, sweating, warm skin, and lactic acidosis develop. With heart failure, orthopnea and pulmonary and peripheral edema occur; vasodilation continues, sometimes resulting in shock. Infantile beriberi occurs in infants (usually between the 2nd and 4th mo of life) who are breastfed by thiamine-deficient mothers. Heart failure, aphonia, and absent deep tendon reflexes are characteristic. Laboratory Findings Elevated blood pyruvate and lactate and diminished urinary thiamine excretion (< 50 µg/day) are consistent with the diagnosis of beriberi. Erythrocyte transketolase activity diminishes before and increases after administration of thiamine pyrophosphate (TPP effect) and is a sensitive indicator of tissue stores. Variations in apoenzyme levels in some cases may complicate interpretation of the test. Diagnosis A form of polyneuropathy, which does not respond to thiamine, occurs in uncontrolled or long-standing diabetes mellitus and in alcoholism and is clinically similar to that of thiamine deficiency. Other forms of bilateral symmetric polyneuropathy beginning in the legs are uncommon. Single-nerve neuritides (mononeuropathies), such as sciatica, and polyneuropathies beginning elsewhere in the body are unlikely to be due to thiamine deficiency. Diagnosis of cardiovascular beriberi is difficult when thiamine deficiency is complicated by hypertensive or degenerative heart disease, viral myocardiopathy, or rheumatic fever. A therapeutic trial of thiamine can be helpful in making the diagnosis. Treatment For mild polyneuropathy, 10 to 20 mg/day of thiamine is given in divided doses for 2 wk, followed by a nutritious diet. The dosage is 20 to 30 mg/day for moderate or advanced neuropathy and should be continued for several weeks after the symptoms disappear. The edema and congestion of Shoshin beriberi respond in a few hours to 100 mg/day of thiamine IV, which should be continued for several days, plus bed rest. Heart failure due to beriberi responds poorly to digitalis or diuretics. For Wernicke-Korsakoff syndrome, thiamine 50 to 100 mg IM or IV bid must usually be given for several days, followed by 10 to 20 mg daily until a therapeutic response is obtained. Anaphylactic reactions to IV thiamine unrelated to the dose are rare. Thiamine deficiency is often associated with other B-complex deficiencies, and multiple water-soluble vitamin therapy at 5 to 10 times the RDA is usually advisable for several weeks. This regimen should be followed indefinitely by a nutritious diet supplying one to two times the RDA. Magnesium, a cofactor for transketolase, should be given as magnesium sulfate (1 to 2 mL IM of a 50% solution) with thiamine to correct thiamine resistance and the frequently accompanying hypomagnesemia. Hyponatremia (see Ch. 12) should be corrected slowly, because rapid correction may cause central pontine myelinolysis. Recovery from neurologic deficits is often incomplete in beriberi. In cerebral beriberi, central pontine myelinolysis may be residual. Thiamine dependency: Several inborn errors of metabolism respond to pharmacologic doses of thiamine (5 to 20 mg/day). These include a megaloblastic anemia of unknown mechanism, lactic acidosis due to low activity of liver pyruvate dehydrogenase, and ketoaciduria due to low activity of branched-chain keto acid dehydrogenases. Quote Link to comment Share on other sites More sharing options...
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