Heart, thiamin deficiency

Thiamin Deficiency Affects the Nervous System Heart... 

Thiamin deficiency can result in three distinct syndromes a chronic peripheral neuritis, beriberi, which may or may not be associated with heart ilure and edema acute pernicious (fulminating) beriberi (shoshin beriberi), in which heart failure and metabolic abnormalities predominate, without peripheral neuritis and Wernicke s encephalopathy with KorsakofPs psychosis, which is associated especially with alcohol and dmg abuse. The central role of thiamin diphosphate in... 

Inadequate nutrition and conditions which are complicated by malabsorption may lead to thiamine deficiency. Beriberi, a diet-deficiency disease, is especially prevalent in those parts of the East where the diet consists mainly of polished rice. The disease is characterized by neuritis but may also lead to serious heart failure. Recovery is prompt when adequate amounts of vitamin B1 are restored to the diet. Severe deficiency as can occur in alcoholics may lead to Wernicke s encephalopathy, often accompanied by Korsakoff s syndrome. Care should be taken with intravenous substitution with thiamine in these cases to prevent serious complications like vascular collapse with hypotension, respiratory distress or an-gioedema. 

The characteristic disease caused by prolonged thiamin deficiency is beriberi, the symptoms of which include oedema, enlarged heart, abnormal heart rhythms, heart failure, wasting, weakness, muscular problems, mental confusion and paralysis. 

In cattle, a thiamine deficiency causes podioencephalomalcia (PEM), characterized by blindness, decreased feed intake, incoordination, failure of rumen to contract, spasms, and paralysis. In swine, a deficiency retards growth and sometimes causes cyanosis (insufficient oxygen in blood), enlarged heart, accompanied by fatly degeneration of heart muscles. Chicks suffer from paralysis of peripheral nerves, causing polyneuritis (head drawn back). 

Individuals on long-term diuretic therapy may also experience elevated levels of homocysteine, an amino acid regulated by folate. High homocysteine levels increase the risk of heart disease. Thiamin, or vitamin Bj, depletion is another possible side effect of loop diuretics. Individuals with thiamin deficiencies are at risk for fatigue, heart enlargement, muscle cramps, heart rate irregularities, and impaired mental function. 

Thiamin that is not bound to plasma proteins is rapidly filtered at the glomerulus. Diuresis increases the excretion of the vitamin, and patients who are treated with diuretics are potentially at risk of thiamin deficiency. Some of the diuretics used in the treatment of hypertension may also inhibit cardiac (and other tissue) uptake of thiamin, thus further impairing thiamin status, which may be a factor in the etiology of heart failure (Suter and Vetter, 2000). 

Together with the fall in pymvate dehydrogenase, there is a fall in the concentration of ATP in the heart, although the ATPiADP ratio in most tissues is not affected by thiamin deficiency (McCandless et al., 1970). 

Patients with congestive heart failure taking high doses of furosemide can develop thiamine deficiency, which is improved by thiamine supplementation. There is whole-blood thiamine phosphate deficiency, but no reduction in the storage form of thiamine, thiamine diphosphate. These observations suggest that thiamine supplementation may not be necessary in elderly patients taking furosemide for congestive heart failure (5). 

Thiamine deficiency resulting in beriberi usually occurs because of excessive alcohol intake, which interferes with thiamine absorption. In the early stages, the person tires easily and the limbs feel heavy and weak. In an advanced stage of wet beriberi,.symptoms include neuromuscular problems enlarged heart (with tachycardia), peripheral edema, and weakness and malaise. These symptoms usually respond to thiamine administration. 

Thiamine absorption occurs primarily in the proximal small intestine by both a saturable (thiamine transporter) process at low concentration (Ipmol/L, or lower) and by simple passive diffusion beyond that, though percentage absorption diminishes with increased dose. The absorbed thiamine undergoes intracellular phosphorylation, mainly to the pyrophosphate, but at the serosal side 90% of the transferred thiamine is in the firee form. Thiamine uptake is enhanced by thiamine deficiency and reduced by thyroid hormone, diabetes, and ethanol ingestion. The gene for the specific thiamine transporter has been identified, and the transporter cloned. Thiamine is carried by the portal blood to the liver. The firee vitamin occurs in the plasma, but the coenzyme, TPP, is the primary cellular component. Approximately 30 mg is stored in the body with 80% as the pyrophosphate, 10% as triphosphate, and the rest as thiamine and its monophosphate. About half of the body stores are found in skeletal muscles, with much of the remainder in heart, liver, kidneys, and nervous tissues (including the brain, which contains most of the triphosphate). 

Beriberi, a neurologic and cardiovascular disorder, is caused by adi etary deficiency of thiamine (also called vitamin B,). The disease has been and continues to be a serious health problem in the Far East because rice, the major food, has a rather low content of thiamine. This deficiency is partly ameliorated if the whole rice grain is soaked in water before milling some of the thiamine in the husk then leaches into the rice kernel. The problem is exacerbated if the rice is polished, because only the outer layer contains significant amounts ot thiamine. Beriberi is also occasionally seen in alcoholics who are severely malnourished and thus thiamine deficient. The disease is characterized by neurologic and cardiac symptoms. Damage to the peripheral nervous system is expressed as pain in the limbs, weakness of the musculature, and distorted skin sensation. The heart may be enlarged and the cardiac output inadequate. 

Thiamine, also known as vitamin B, is fairly ubiquitous. Thiamine deficiency is uncommon except in alcoholics as a result of nutritional deficiencies and malabsorption. The classic clinical triad of dementia, ataxia (difficulty with walking), and eye findings may be seen, but more commonly, only forgetfulness is noted. Sometimes, thiamine deficiency can lead to vague symptoms such as leg numbness or tingling. Because thiamine is water soluble, it can be added to intravenous fluids and administered in that way. Other manifestations include beri beri, which is cardiac involvement leading to a high cardiac output, and vasodilation. Affected patients often feel warm and flushed, and they can have heart failure. 

In Al Martini s heart failure, which is caused by a dietary deficiency of the vitamin thiamine, pyruvate dehydrogenase, a-ketoglutarate dehydrogenase, and the branched chain a-keto acid dehydrogenase complexes are less functional than normal. Because heart muscle, skeletal muscle, and nervous tissue have a high rate of ATP production from the NADH produced by the oxidation of pyruvate to acetyl CoA and of acetyl CoA to COj in the TCA cycle, these tissues present with the most obvious signs of thiamine deficiency. 

Al Martini. A1 Martini presents a second time with an alcohol-related J high output form of heart failure sometimes referred to as wet beriberi, or as the beriberi heart (see Chapter 9). The term wet refers to the fluid retention which may eventually occur when left ventricular contractility is so compromised that cardiac output, although initially relatively high, cannot meet the demands of the peripheral vascular beds, which have dilated in response to the thiamine deficiency. 

The cardiomyopathy is directly related to a reduction in the normal biochemical function of the vitamin thiamine in heart muscle. Inhibition of the a-keto acid dehydrogenase complexes causes accumulation of a-keto acids in heart muscle (and in blood), resulting in a chemically-induced cardiomyopathy. Impairment of two other functions of thiamine may also contribute to the cardiomyopathy. Thiamine pyrophosphate serves as the coenzyme for transketolase in the pentose phosphate pathway, and pentose phosphates accumulate in thiamine deficiency. In addition, thiamine triphosphate (a different coenzyme form) may function in Na conductance channels. 

Beriberi is a neurological and cardiovascular disorder that is caused by a deficiency of thiamine (also called vitamin Bj). It has been a serious health problem in Asia and continues to be in those places where rice is the main staple food. The problem is exacerbated if the rice is dehusked (polished) because only the outer layers of the seeds contain appreciable amounts of thiamine. Beriberi also occurs in some malnourished chronic alcoholics, so to avoid this problem in some countries certain alcohol-containing drinks are fortified with thiamine. Beriberi is characterized by pain in the limbs, weak muscles, abnormal skin sensation, and an enlarged heart with inadequate cardiac output. Which biochemical processes are affected by thiamine deficiency ... 

The incidence of thiamine deficiency in alcoholics is 30-80% (Homewood and Bond, 1999). Factors that promote thiamine deficiency in alcoholics include poor thiamine intake, decreased activation of thiamine to thiamine pyrophosphate(TPP), decreased hepatic storage, decreased intestinal thiamine transport and impairment of thiamine absorption (see Table 14.3) (Breen et al, 1985 Hoyumpa, 1980). Although thiamine is stored in various sites, including skeletal muscles, heart, kidneys and brain, the Uver remains the main storage site. Due to the reasons cited above, hepatic thiamine content may be reduced by 73% in patients with severe, chronic alcoholic liver disease. In addition, ethanol has been shown to promote thiamine release from the liver (Hoyumpa, 1980). 

Seligmann, H., Halkln, H., Rauchfleisch, S., Kaufmann, N., Motro, M., Vered, Z., and Ezra, D. (1991). Thiamine deficiency in patients with congestive heart failure receiving long-term furo-semide therapy a pilot study. Am. J. Med. 91 151-155. 

An explanation for the pathogenesis of the lesions observed in thiamine deficiency would seem to follow logically from these biochemical observations, for in the thiamine-deficient animal, at least two enzymes involved in the Krebs cycle are blocked. The block of pyruvic decarboxylase prevents the entry of the products of glycolysis into the Krebs cycle. The block of a-ketoglutarate decarboxylase restricts the oxidation of both carbohydrates and fatty acids. A severe metabolic distortion follows, and one of the main manifestations of the distortion is a reduction of the amount of chemical energy available in the form of ATP. Clearly, those organs that suffer the most from such alterations are those that are metabolically most active, and the heart and the peripheral nervous system surely qualify as such. 

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