STUDY - Technical - New Dacian's Medicine
Vitamin
Deficiency and Excess (1)
Translation Draft
Vitamin imbalances have several roles in human ailments. The deficiency of a single vitamin is rarely endemic, even in developing countries, with the lack of vitamins occurring much more frequently either in general malnutrition, inadequate feeding, as a complication of diseases, such as malabsorption or alcoholism, as a consequence of complex therapies such as hemodialysis or total parenteral nutrition, or as a result of a congenital metabolism error.
Excess vitamin is, at the moment, much more common than deficiency. In the physiology of vitamins can be emphasized several elements: 1. the impossibility of the human body to synthesize organic compounds, so that it depends on their exogenous intake, being the result of a mutation, the addition of vitamins in the diet being a form of treatment in cases of congenital metabolic errors (In some cases, such as limiting the synthesis capacity of thiamine , the disease can occur in virtually any species in the animal kingdom, the mutation occurring early in evolution.
In other situations, for example, the monogenic defect that prevents the synthesis of ascorbic acid, the human race "shares" the disease with only a few species, such as guinea pigs), 2. what individualizes vitamin intake among other organic constituents is that, unlike amino acids and fatty acids, for example, the need for vitamins is very low (This is because vitamins do not have a plastic or energetic role, but function as prosthetic groups for quantitative minor tissue constituents or as catalytic cofactors in biological reactions. Like most catalysts, vitamins are needed in small amounts), 3. vitamin deficiency (e.g. pantothenic acid) has never been described in humans, which means either that these vitamins are ubifiate in all food sources or that they are preserved very effectively in the body (deficiency becomes expressed, if indeed, only in the context of mixed vitamin and nutritional deficits), 4. alcoholism is the ground on which many vitamin deficiencies develop (This is the consequence of multiple factors that intersect and that include decreased nutritional intake, alteration of vitamin absorption and storage and, in some cases, predisposing genetic factors), 5. the biochemical means available to highlight vitamin deficiency are limited, and the role of these deficiencies in the disease investigated is not always recognized, due to the fact that non-specific vitamin therapy is a part of standard supportive therapy (Consequently, the suspicion of the diagnosis of hypovitaminosis in the presence of suggestive manifestations is essential, and the demonstration of the positive effects of vitamin therapy can constitute the most accurate way of confirming dia Gnostic), 6. hypervitaminosis results either by excessive food intake or, more frequently, by voluntary ingestion (toxic syndromes produced by excess fat-soluble vitamins A and D are well known, while the consequences of the toxicity of fat-soluble vitamins are inconsistent and much less understood).
Let's customize the presentation of the main vitamin deficiencies, starting with the deficiency of niacin, with its manifestation, pelagra. From the point of view of biochemistry, niacin is the generic name for nicotinic acid (pyridin-3-carboxylic acid) and derivatives that exert identical activity to it. In a certain sense, niacin is not a vitamin, it can be synthesized in the body from tryptophan (in humans, from 60 mg in dietary tryptophan results 1 mg niacin). Therefore, an appropriate diet should take into account both tryptophan and niacin. Many foods, especially cereals, contain forms related to niacin, which is not available for nutrition. Vitamin is rapidly absorbed from the gut through active and passive transport mechanisms.
The absorption capacity of niacin is 3-4 g/day (in humans). Approximately one-fifth is decarboxylated to nicotinuric acid, and the rest is excreted through urine in the form of methylated products, especially N-methylnicotinamide (NMN) and N-methyl-2-pyridone-5-caroxiamide. In terms of mechanism of action, niacin is an essential component of nicotinamide-adenin-dinucleotide (NAD) and nicotinamid-adenin-dinucleotide phosphate (NADP), coenzymes for many redox reactions. Unlike other vitamins, the requirement of niacin does not seem to increase during pregnancy. In the case of experimental depletion, after establishing a diet without niacin and tryptophan, urinary excretion of niacin metabolites reaches minimum values (less than 1.5 mg/day) after 1-2 months.
The deficiency is clinically manifested immediately afterwards and consists of dermatitis, glossitis, stomatitis, diarrhea, proctitis, mental depression, abdominal pain, vaginitis, dysfunction and amenorrhea, manifestations similar to those in the pelagr. Clinically, pelagra has been an endemic disease in South America and several regions of the globe. Endemic damage is usually associated with increased consumption of corn and millet (it can be cured by administration of niacin - however, the fact that large populations provide their food through a diet in which corn is the main food but does not exhibit endemic pelage, suggests that the relationship between it and corn consumption is not linear). The niacinic equivalent (available niacin and tryptophan) of maize, although reduced, is not lower than other cereals not associated with endemic pelagra.
Consequently, the concept of pelagre pathogenesis has evolved from the role of a pure vitamin deficiency or a mixed deficiency of tryptophan and niacin available to a much more complicated etiology. The condition may be due to an imbalance in the amino acid content of the diet or a complex caren. Corn milling influences the bioavailability of niacin in cereals. Food preparation in Latin America involves treating corn with alkaline substances, which is probably helping to hydrolyze the bound nicotinic acid and inactivate toxins accumulated in mold-contaminated grains. Cereal degermination during grinding may inhibit the release of related niacin.
The effect of these treatments could be prevention, i.e. predisposition, to the appearance of pelagre, when maize is a major element of the diet. Whatever the cause, endemic pelagra has disappeared at the same time as improving the level of nutritional education and the widespread use of niacin supplementation, but it still appears in endemic form, for example, among refugees. Pelagra is a rare manifestation of two changes in tryptophan metabolism, carcinoid syndrome (in which up to 60% of tryptophan is catabolized on a metabolic pathway, usually minor) and Hartnup disease, a hereditary condition in which several amino acids, including tryptophan, are absorbed in small amounts from ingested foods. In both cases, pelagra is due to a decrease in the availability of niacin equivalences and can be cured by administering amounts of niacin.
Pelagra is a chronic emacian disease, typically associated with dermatitis, dementia and diarrhea. Dermatitis is bilateral, symmetrical, occurs in areas exposed to sunlight, being photosensitive. Psychiatric signs are pronounced: fatigue, insomnia and apathy can precede the development of an encephalopathy characterized by confusion, disorientation, hallucinations, memory loss and ultimately organic psychosis. The coexistence of other vitamin deficiencies can cause paresthesia and polyneuritis. When present, diarrhea results from the generalization of inflammation in the mucous membranes (other abnormalities of the mucous membranes include achlorhydria, glossitis, stomatitis and vaginitis). Skin lesions are characterized by hyperkeratosis, hyperpigmentation, descuamation. Evolution is progressive for several years, death usually occurring secondary to complications.
The relationship between the coenzyme functions of NAD and NADP and the symptoms was not specified. Psychiatric disorders in the pelagr may be due to a decrease in the conversion of tryptophan to serotonin. There is no specific diagnostic test, based on clinical suspicion and positive response to replacement therapy. As can be inferred, urinary excretion of nicotinic acid and tryptophan metabolites is low, but no more so than in patients with general malnutrition. The plasma levels of tryptophan and NAD, erythrocytic NADP are also low. Taking small amounts of niacin (10 mg/day) at the same time as a sufficient amount of tryptophan from the diet is enough to produce the cure of endemic pelage. Large amounts of niacin (40-200 mg/day) may be needed in Hartnup disease and carcinoid syndrome.
Let's see now what is with thiamine deficiency and its manifestation, "disease" Beriberi! From the point of view of biochemistry, thiamine contains fragments of pyridimine and thiazole joined by a methylene bridge. The vitamin is synthesized by a multitude of plants and microorganisms, but not by animals. However, rats and pigeons fed a thiamine-free diet may not get the disease if they receive large amounts of pyrimidine and thiazole fragments, suggesting some ability to couple the two subunits. Reduced amounts are synthesized in the gastrointestinal tract by the microbial flora. Thiamine is absorbed both by active transport and by passive diffusion.
The intestinal absorption capacity in humans is 5 mg/day. Approximately 25-30 mg are stored, 80% in the form of thianine diphosphate (pyrophosphate), 10% as thianine triphosphate, and the rest as thiathin monophosphate. Large amounts are found in the skeletal muscle, heart, liver, kidney and brain. Thiamine is inactivated by separation into the two components by a number of enzymes (thiaminases). Some metabolites are excreted urinaryly, mainly thiamine itself (tubular excretion), an aethylated derivative and derivatives of thiazole acetate and carboxylate pyrimidine. From the point of view of the mechanism of action, thiamindiphosphate acts as a coenzyme in reactions that cleave carbon-carbon-oxidative decarboxylation of alpha-cetoacids (pyruvate and alpha-cetoglutarate) and cetoanalogues of leucine, isoleucin and valin and transcetolation reactions in the pentophoszofate cycle.
Many manifestations of thiamine deficiency are the result of inhibition of these enzyme reactions and/ or accumulation of proximal metabolites. Apart from its function in general metabolism, thiamine can play a specific role at the neural level (thiamine and its esters are present in the anoxic membrane and electrical stimulation of the nerves produces hydrolysis and release of thiamindiphosphate and triphosphate).
Vitamin is widespread in food and is lacking in oils, lipids, tapioca starch, or refined sugar. In plant products it is mostly in the form of thiathine. The external coating of grain grains is very rich in vitamin (hence it is inferred that husked or ground rice is a poor source). In animal tissue, thiamine is present mainly in the form of phosphoesters. They dephosphorylize under the action of intestinal phosphatases and only the free form of the vitamin is absorbed. Considerable losses occur if food is prepared at temperatures above 100 degrees Celsius.
Several factors influence the absorption and metabolism of the vitamin (and alter daily needs). One of these is the presence of thiamine as in foods such as fresh fish, clams, shrimp, molluscs, in some raw animal tissues and in microorganisms in the colon. The second is the change in daily need (when lipids are an important part of the diet the need decreases, and when carbohydrates increase in the diet also increases the need for thiamine). Pregnancy, lactation, thyrotoxicosis and fever increase vitamin needs. Large losses of thiamine may occur during therapy with diuretics, hemodialysis, peritoneal dialysis and diarrhoea. Absorption is carried out in states of malabsorption, alcoholism, chronic malnutrition and folate deficiency.
In the case of experimental deplation, after the establishment of a diet without thiamine, its urinary excretion decreased to 5% of the control value after one week, to 2 weeks becoming undetectable. Excretion of pyrimidine and thiazole catabolites remained unchanged for one month, demonstrating that the body's reserves are used progressively when intake is reduced. One week after establishing the diet, patients experienced resting tachycardia followed by the appearance of weakness, decreased deep tendinous reflexes and sometimes sensory neuropathy.
Symptoms included general malaise, headache, nausea and muscle tingling. Parallel to the occurrence of these symptoms decreased the activity of erythrocytic transcetolase. After one week of taking thiamine (2 mg/day) all abnormal signs disappeared and subjective symptoms disappeared after 2 weeks. Experimental deletation in humans has not been performed until severe manifestations occur. For clinical deficiency, in developed countries, thiamine deficiency occurs in alcoholics, malnourished or in special situations such as chronic peritoneal dialysis, hemodialysis, refueling after starvation or after administration of glucose in patients with decreased thiamine without clinical manifestations.
In developing countries, the deficiency is due to consumption of rice flour or foods containing thiamineases or (possibly) other antithiaminic factors. The occurrence of deficiency in alcoholics is due to poor intake, impaired absorption and storage, acceleration of the degradation of thiamindiphosphate, and increased energy consumption. However, clinical manifestations occur only in some alcoholics and not in all chronically malnourished people. Genetic factors may play a role in the existence of susceptibility. The two main manifestations of thiamine deficiency involve the cardiovascular system (wet beriberi) and the nervous system (dry beriberi and Wernicke-Korsakoff syndrome).
Typically, patients show mixed signs involving both systems, but pure cardiovascular, neuropathic or cerebral forms may also occur. The relative predominance of these manifestations is partly related to the duration and severity of the deficiency, the degree of physical exertion and caloric intake. Intense physical activity, increased carbohydrate intake and a moderate degree of chronic deficiency favour the appearance of wet form of beriberi, with signs of absent or reduced peripheral neuritis, while a thiaminic deficiency associated with caloric restriction and relative inactivity favors the form of dry beers.
Heart damage in beriberi includes three major physiopathological disturbances: 1. peripheral vasodilation leading to increased cardiac output, 2. hydrosalin retention and consecutive edema and 3. global heart failure. In the chronic form, peripheral vasodilation leads to increased arteriovenous shunt, increased circulatory speed, tachycardia, increased heart rate and venous congestion, characterized by increased peripheral venous pressure, increased telediastolic pressure in the right ventricle, decreased arteriovenous oxygen extraction, sanded retention and edema. Decreased cerebral and renal blood flow, as well as increased muscle irrigation are commonly encountered. Heart rate increases, so trying to compensate for low peripheral vascular resistance, ventricular exertion, blood pressure and pulmonary pressure tend to increase.
During the administration of tiamine to compensate for the deficiency, aggravation of hypertension may occur, probably due to the closure of arteriovenous shunts and transient volemy overload. In acute fulminant cardiovascular beers (shoshin), myocardial injury is the main cause of dyspnea, agitation, anxiety, from cardiovascular collapse, death can occur in hours or days. The objective examination highlights peripheral cyanosis, tachycardia, marked cardiomegaly, hepatomegaly, arterial noises and jugular turgidity.
Venous pressure is increased and circulation time is fast. Due to the fulminant evolution, edemas may be missing or minimal. Rapid administration of tiamine restores peripheral vascular resistance, but improvement in myocardial condition may occur late, so heart failure may persist during treatment. There are three types of nervous system damage: peripheral neuropathy, Werniscke encephalopathy (cerebral beriberi) and Korsakoff syndrome. Neuropathy may or may not be painful and is characterized by symmetrical sensory, motor and reflex impairment, predominantly affecting the distal segments of the limbs.
Histological lesion consists in the non-inflammatory degeneration of the myelin tea. No distinction can be made between beriberi neuropathy based on clinical criteria. Wernicke's encephalopathy is usually established in a sequence consisting of vomiting, nystagmus (more commonly horizontal), paralysis of the right muscles that generate uni/bilateral ophthalmoplegia (and decrease disthonament of the nystagmus), fever, ataxia and progressive mental deterioration, which may end in a global confusional state, whether or not followed by coma or death. The clinical condition improves after taking thaain, although Korsakoff syndrome may occur.
Thus, eye paralysis is corrected, nystagmus is reduced (by half), ataxia improves or disappears (at two thirds), the state of global confusion disappears and is replaced by Korsakoff syndrome. The latter consists of retrograde amnesia, impaired learning capacity and (usually) confabulation. The patient is usually alert, responds to stimuli and shows no significant deterioration in behavior. Recovery (complete or partial) of Korsakoff syndrome occurs only in half of cases.
In sum, it can be said that Wernicke's encephalopathy and amnesiac psychosis in Korsakoff syndrome are not separate clinical entities (in fact, the evolution of ocular and ataxic signs, the transformation of the global confusional state into a confabulator amnesia syndrome and the development of the state of non-conftabular amnesia represent successive stages of recovery in the same process). Biochemical tests to detect thiamindeficience deficiency include the determination of saunguine thiamine, pyruvate, alpha-cetoglutarate, lactate and glycoxilate (measurement of urinary excretion of thiamine and its metabolites, thiamine loading test and urinary methylglioxal dosing). The most accurate test is the measurement of the activity of transcetolation of whole blood or erythrocytes.
Any improvement in enzyme activity resulting from the administration of thiamindiphosphate (TPP) is known as the effect of TPP and is expressed as a percentage. One can talk about a state of deficiency if the activity of the enzyme increases by more than 15% by adding thiamindiphosphate. Isolated determination of transcetolase levels is not useful, but highlighting the increase in activity after treatment associated with a positive TPP test prior to the establishment of therapy suggests the existence of thiamin deficiency. Another diagnostic criterion is the presence of the cynical response to the administration of tiamine. clinical improvement can be spectacular in the cardiovascular form of beriberi, 12 hours after the onset of therapy blood pressure increasing to normal values and heart rate decreasing, in the next 1-2 days producing the resumption of normal diuresis and reduction of heart size. Prompt administration of thiamine is indicated when beriberi is diagnosed with certain or suspected. The dose is 50 mg/ day, administered intramuscularly for several days, after which 2.5 to 5 mg/day per bone may be administered. Quantities greater than those mentioned are not usually absorbed. All patients should receive additional with other hydrosoluble vitamins in therapeutic quantities.
There's more to be said for congenital metabolism errors that respond to thaaine. These conditions are characterized by the fact that patients respond positively to pharmacological doses of thiahin, including those suffering from thiamino-sensitive megaloblastic anaemia due to poor cellular transport of thiamine (thiamin-sensitive lactic acidosis caused by decreased activity of the purivat dehydrogenase complex, ketonuria with branched chains responsive to thiamine, which is due to a low activity of dehydrogenase of branched chain alpha-ceto acids and a group of subjects with Leigh encephalopathy due to an abnormality of the E1 alpha subunit of the pyruvate dehydrogenase).
Long post... but I'm done...
Vitamin imbalances have several roles in human ailments. The deficiency of a single vitamin is rarely endemic, even in developing countries, with the lack of vitamins occurring much more frequently either in general malnutrition, inadequate feeding, as a complication of diseases, such as malabsorption or alcoholism, as a consequence of complex therapies such as hemodialysis or total parenteral nutrition, or as a result of a congenital metabolism error.
Excess vitamin is, at the moment, much more common than deficiency. In the physiology of vitamins can be emphasized several elements: 1. the impossibility of the human body to synthesize organic compounds, so that it depends on their exogenous intake, being the result of a mutation, the addition of vitamins in the diet being a form of treatment in cases of congenital metabolic errors (In some cases, such as limiting the synthesis capacity of thiamine , the disease can occur in virtually any species in the animal kingdom, the mutation occurring early in evolution.
In other situations, for example, the monogenic defect that prevents the synthesis of ascorbic acid, the human race "shares" the disease with only a few species, such as guinea pigs), 2. what individualizes vitamin intake among other organic constituents is that, unlike amino acids and fatty acids, for example, the need for vitamins is very low (This is because vitamins do not have a plastic or energetic role, but function as prosthetic groups for quantitative minor tissue constituents or as catalytic cofactors in biological reactions. Like most catalysts, vitamins are needed in small amounts), 3. vitamin deficiency (e.g. pantothenic acid) has never been described in humans, which means either that these vitamins are ubifiate in all food sources or that they are preserved very effectively in the body (deficiency becomes expressed, if indeed, only in the context of mixed vitamin and nutritional deficits), 4. alcoholism is the ground on which many vitamin deficiencies develop (This is the consequence of multiple factors that intersect and that include decreased nutritional intake, alteration of vitamin absorption and storage and, in some cases, predisposing genetic factors), 5. the biochemical means available to highlight vitamin deficiency are limited, and the role of these deficiencies in the disease investigated is not always recognized, due to the fact that non-specific vitamin therapy is a part of standard supportive therapy (Consequently, the suspicion of the diagnosis of hypovitaminosis in the presence of suggestive manifestations is essential, and the demonstration of the positive effects of vitamin therapy can constitute the most accurate way of confirming dia Gnostic), 6. hypervitaminosis results either by excessive food intake or, more frequently, by voluntary ingestion (toxic syndromes produced by excess fat-soluble vitamins A and D are well known, while the consequences of the toxicity of fat-soluble vitamins are inconsistent and much less understood).
Let's customize the presentation of the main vitamin deficiencies, starting with the deficiency of niacin, with its manifestation, pelagra. From the point of view of biochemistry, niacin is the generic name for nicotinic acid (pyridin-3-carboxylic acid) and derivatives that exert identical activity to it. In a certain sense, niacin is not a vitamin, it can be synthesized in the body from tryptophan (in humans, from 60 mg in dietary tryptophan results 1 mg niacin). Therefore, an appropriate diet should take into account both tryptophan and niacin. Many foods, especially cereals, contain forms related to niacin, which is not available for nutrition. Vitamin is rapidly absorbed from the gut through active and passive transport mechanisms.
The absorption capacity of niacin is 3-4 g/day (in humans). Approximately one-fifth is decarboxylated to nicotinuric acid, and the rest is excreted through urine in the form of methylated products, especially N-methylnicotinamide (NMN) and N-methyl-2-pyridone-5-caroxiamide. In terms of mechanism of action, niacin is an essential component of nicotinamide-adenin-dinucleotide (NAD) and nicotinamid-adenin-dinucleotide phosphate (NADP), coenzymes for many redox reactions. Unlike other vitamins, the requirement of niacin does not seem to increase during pregnancy. In the case of experimental depletion, after establishing a diet without niacin and tryptophan, urinary excretion of niacin metabolites reaches minimum values (less than 1.5 mg/day) after 1-2 months.
The deficiency is clinically manifested immediately afterwards and consists of dermatitis, glossitis, stomatitis, diarrhea, proctitis, mental depression, abdominal pain, vaginitis, dysfunction and amenorrhea, manifestations similar to those in the pelagr. Clinically, pelagra has been an endemic disease in South America and several regions of the globe. Endemic damage is usually associated with increased consumption of corn and millet (it can be cured by administration of niacin - however, the fact that large populations provide their food through a diet in which corn is the main food but does not exhibit endemic pelage, suggests that the relationship between it and corn consumption is not linear). The niacinic equivalent (available niacin and tryptophan) of maize, although reduced, is not lower than other cereals not associated with endemic pelagra.
Consequently, the concept of pelagre pathogenesis has evolved from the role of a pure vitamin deficiency or a mixed deficiency of tryptophan and niacin available to a much more complicated etiology. The condition may be due to an imbalance in the amino acid content of the diet or a complex caren. Corn milling influences the bioavailability of niacin in cereals. Food preparation in Latin America involves treating corn with alkaline substances, which is probably helping to hydrolyze the bound nicotinic acid and inactivate toxins accumulated in mold-contaminated grains. Cereal degermination during grinding may inhibit the release of related niacin.
The effect of these treatments could be prevention, i.e. predisposition, to the appearance of pelagre, when maize is a major element of the diet. Whatever the cause, endemic pelagra has disappeared at the same time as improving the level of nutritional education and the widespread use of niacin supplementation, but it still appears in endemic form, for example, among refugees. Pelagra is a rare manifestation of two changes in tryptophan metabolism, carcinoid syndrome (in which up to 60% of tryptophan is catabolized on a metabolic pathway, usually minor) and Hartnup disease, a hereditary condition in which several amino acids, including tryptophan, are absorbed in small amounts from ingested foods. In both cases, pelagra is due to a decrease in the availability of niacin equivalences and can be cured by administering amounts of niacin.
Pelagra is a chronic emacian disease, typically associated with dermatitis, dementia and diarrhea. Dermatitis is bilateral, symmetrical, occurs in areas exposed to sunlight, being photosensitive. Psychiatric signs are pronounced: fatigue, insomnia and apathy can precede the development of an encephalopathy characterized by confusion, disorientation, hallucinations, memory loss and ultimately organic psychosis. The coexistence of other vitamin deficiencies can cause paresthesia and polyneuritis. When present, diarrhea results from the generalization of inflammation in the mucous membranes (other abnormalities of the mucous membranes include achlorhydria, glossitis, stomatitis and vaginitis). Skin lesions are characterized by hyperkeratosis, hyperpigmentation, descuamation. Evolution is progressive for several years, death usually occurring secondary to complications.
The relationship between the coenzyme functions of NAD and NADP and the symptoms was not specified. Psychiatric disorders in the pelagr may be due to a decrease in the conversion of tryptophan to serotonin. There is no specific diagnostic test, based on clinical suspicion and positive response to replacement therapy. As can be inferred, urinary excretion of nicotinic acid and tryptophan metabolites is low, but no more so than in patients with general malnutrition. The plasma levels of tryptophan and NAD, erythrocytic NADP are also low. Taking small amounts of niacin (10 mg/day) at the same time as a sufficient amount of tryptophan from the diet is enough to produce the cure of endemic pelage. Large amounts of niacin (40-200 mg/day) may be needed in Hartnup disease and carcinoid syndrome.
Let's see now what is with thiamine deficiency and its manifestation, "disease" Beriberi! From the point of view of biochemistry, thiamine contains fragments of pyridimine and thiazole joined by a methylene bridge. The vitamin is synthesized by a multitude of plants and microorganisms, but not by animals. However, rats and pigeons fed a thiamine-free diet may not get the disease if they receive large amounts of pyrimidine and thiazole fragments, suggesting some ability to couple the two subunits. Reduced amounts are synthesized in the gastrointestinal tract by the microbial flora. Thiamine is absorbed both by active transport and by passive diffusion.
The intestinal absorption capacity in humans is 5 mg/day. Approximately 25-30 mg are stored, 80% in the form of thianine diphosphate (pyrophosphate), 10% as thianine triphosphate, and the rest as thiathin monophosphate. Large amounts are found in the skeletal muscle, heart, liver, kidney and brain. Thiamine is inactivated by separation into the two components by a number of enzymes (thiaminases). Some metabolites are excreted urinaryly, mainly thiamine itself (tubular excretion), an aethylated derivative and derivatives of thiazole acetate and carboxylate pyrimidine. From the point of view of the mechanism of action, thiamindiphosphate acts as a coenzyme in reactions that cleave carbon-carbon-oxidative decarboxylation of alpha-cetoacids (pyruvate and alpha-cetoglutarate) and cetoanalogues of leucine, isoleucin and valin and transcetolation reactions in the pentophoszofate cycle.
Many manifestations of thiamine deficiency are the result of inhibition of these enzyme reactions and/ or accumulation of proximal metabolites. Apart from its function in general metabolism, thiamine can play a specific role at the neural level (thiamine and its esters are present in the anoxic membrane and electrical stimulation of the nerves produces hydrolysis and release of thiamindiphosphate and triphosphate).
Vitamin is widespread in food and is lacking in oils, lipids, tapioca starch, or refined sugar. In plant products it is mostly in the form of thiathine. The external coating of grain grains is very rich in vitamin (hence it is inferred that husked or ground rice is a poor source). In animal tissue, thiamine is present mainly in the form of phosphoesters. They dephosphorylize under the action of intestinal phosphatases and only the free form of the vitamin is absorbed. Considerable losses occur if food is prepared at temperatures above 100 degrees Celsius.
Several factors influence the absorption and metabolism of the vitamin (and alter daily needs). One of these is the presence of thiamine as in foods such as fresh fish, clams, shrimp, molluscs, in some raw animal tissues and in microorganisms in the colon. The second is the change in daily need (when lipids are an important part of the diet the need decreases, and when carbohydrates increase in the diet also increases the need for thiamine). Pregnancy, lactation, thyrotoxicosis and fever increase vitamin needs. Large losses of thiamine may occur during therapy with diuretics, hemodialysis, peritoneal dialysis and diarrhoea. Absorption is carried out in states of malabsorption, alcoholism, chronic malnutrition and folate deficiency.
In the case of experimental deplation, after the establishment of a diet without thiamine, its urinary excretion decreased to 5% of the control value after one week, to 2 weeks becoming undetectable. Excretion of pyrimidine and thiazole catabolites remained unchanged for one month, demonstrating that the body's reserves are used progressively when intake is reduced. One week after establishing the diet, patients experienced resting tachycardia followed by the appearance of weakness, decreased deep tendinous reflexes and sometimes sensory neuropathy.
Symptoms included general malaise, headache, nausea and muscle tingling. Parallel to the occurrence of these symptoms decreased the activity of erythrocytic transcetolase. After one week of taking thiamine (2 mg/day) all abnormal signs disappeared and subjective symptoms disappeared after 2 weeks. Experimental deletation in humans has not been performed until severe manifestations occur. For clinical deficiency, in developed countries, thiamine deficiency occurs in alcoholics, malnourished or in special situations such as chronic peritoneal dialysis, hemodialysis, refueling after starvation or after administration of glucose in patients with decreased thiamine without clinical manifestations.
In developing countries, the deficiency is due to consumption of rice flour or foods containing thiamineases or (possibly) other antithiaminic factors. The occurrence of deficiency in alcoholics is due to poor intake, impaired absorption and storage, acceleration of the degradation of thiamindiphosphate, and increased energy consumption. However, clinical manifestations occur only in some alcoholics and not in all chronically malnourished people. Genetic factors may play a role in the existence of susceptibility. The two main manifestations of thiamine deficiency involve the cardiovascular system (wet beriberi) and the nervous system (dry beriberi and Wernicke-Korsakoff syndrome).
Typically, patients show mixed signs involving both systems, but pure cardiovascular, neuropathic or cerebral forms may also occur. The relative predominance of these manifestations is partly related to the duration and severity of the deficiency, the degree of physical exertion and caloric intake. Intense physical activity, increased carbohydrate intake and a moderate degree of chronic deficiency favour the appearance of wet form of beriberi, with signs of absent or reduced peripheral neuritis, while a thiaminic deficiency associated with caloric restriction and relative inactivity favors the form of dry beers.
Heart damage in beriberi includes three major physiopathological disturbances: 1. peripheral vasodilation leading to increased cardiac output, 2. hydrosalin retention and consecutive edema and 3. global heart failure. In the chronic form, peripheral vasodilation leads to increased arteriovenous shunt, increased circulatory speed, tachycardia, increased heart rate and venous congestion, characterized by increased peripheral venous pressure, increased telediastolic pressure in the right ventricle, decreased arteriovenous oxygen extraction, sanded retention and edema. Decreased cerebral and renal blood flow, as well as increased muscle irrigation are commonly encountered. Heart rate increases, so trying to compensate for low peripheral vascular resistance, ventricular exertion, blood pressure and pulmonary pressure tend to increase.
During the administration of tiamine to compensate for the deficiency, aggravation of hypertension may occur, probably due to the closure of arteriovenous shunts and transient volemy overload. In acute fulminant cardiovascular beers (shoshin), myocardial injury is the main cause of dyspnea, agitation, anxiety, from cardiovascular collapse, death can occur in hours or days. The objective examination highlights peripheral cyanosis, tachycardia, marked cardiomegaly, hepatomegaly, arterial noises and jugular turgidity.
Venous pressure is increased and circulation time is fast. Due to the fulminant evolution, edemas may be missing or minimal. Rapid administration of tiamine restores peripheral vascular resistance, but improvement in myocardial condition may occur late, so heart failure may persist during treatment. There are three types of nervous system damage: peripheral neuropathy, Werniscke encephalopathy (cerebral beriberi) and Korsakoff syndrome. Neuropathy may or may not be painful and is characterized by symmetrical sensory, motor and reflex impairment, predominantly affecting the distal segments of the limbs.
Histological lesion consists in the non-inflammatory degeneration of the myelin tea. No distinction can be made between beriberi neuropathy based on clinical criteria. Wernicke's encephalopathy is usually established in a sequence consisting of vomiting, nystagmus (more commonly horizontal), paralysis of the right muscles that generate uni/bilateral ophthalmoplegia (and decrease disthonament of the nystagmus), fever, ataxia and progressive mental deterioration, which may end in a global confusional state, whether or not followed by coma or death. The clinical condition improves after taking thaain, although Korsakoff syndrome may occur.
Thus, eye paralysis is corrected, nystagmus is reduced (by half), ataxia improves or disappears (at two thirds), the state of global confusion disappears and is replaced by Korsakoff syndrome. The latter consists of retrograde amnesia, impaired learning capacity and (usually) confabulation. The patient is usually alert, responds to stimuli and shows no significant deterioration in behavior. Recovery (complete or partial) of Korsakoff syndrome occurs only in half of cases.
In sum, it can be said that Wernicke's encephalopathy and amnesiac psychosis in Korsakoff syndrome are not separate clinical entities (in fact, the evolution of ocular and ataxic signs, the transformation of the global confusional state into a confabulator amnesia syndrome and the development of the state of non-conftabular amnesia represent successive stages of recovery in the same process). Biochemical tests to detect thiamindeficience deficiency include the determination of saunguine thiamine, pyruvate, alpha-cetoglutarate, lactate and glycoxilate (measurement of urinary excretion of thiamine and its metabolites, thiamine loading test and urinary methylglioxal dosing). The most accurate test is the measurement of the activity of transcetolation of whole blood or erythrocytes.
Any improvement in enzyme activity resulting from the administration of thiamindiphosphate (TPP) is known as the effect of TPP and is expressed as a percentage. One can talk about a state of deficiency if the activity of the enzyme increases by more than 15% by adding thiamindiphosphate. Isolated determination of transcetolase levels is not useful, but highlighting the increase in activity after treatment associated with a positive TPP test prior to the establishment of therapy suggests the existence of thiamin deficiency. Another diagnostic criterion is the presence of the cynical response to the administration of tiamine. clinical improvement can be spectacular in the cardiovascular form of beriberi, 12 hours after the onset of therapy blood pressure increasing to normal values and heart rate decreasing, in the next 1-2 days producing the resumption of normal diuresis and reduction of heart size. Prompt administration of thiamine is indicated when beriberi is diagnosed with certain or suspected. The dose is 50 mg/ day, administered intramuscularly for several days, after which 2.5 to 5 mg/day per bone may be administered. Quantities greater than those mentioned are not usually absorbed. All patients should receive additional with other hydrosoluble vitamins in therapeutic quantities.
There's more to be said for congenital metabolism errors that respond to thaaine. These conditions are characterized by the fact that patients respond positively to pharmacological doses of thiahin, including those suffering from thiamino-sensitive megaloblastic anaemia due to poor cellular transport of thiamine (thiamin-sensitive lactic acidosis caused by decreased activity of the purivat dehydrogenase complex, ketonuria with branched chains responsive to thiamine, which is due to a low activity of dehydrogenase of branched chain alpha-ceto acids and a group of subjects with Leigh encephalopathy due to an abnormality of the E1 alpha subunit of the pyruvate dehydrogenase).
Long post... but I'm done...
Love, Understanding and
Gratitude!!!
Dorin, Merticaru