By B. Gorok. Soka University of America.
Alcohol Metabolism Alcohol is metabolized to acetaldehyde by alcohol dehydrogenase in the hepatocyte cytosol discount 75mg tofranil otc anxiety keeping me awake, and then to acetate by acetaldehyde dehydrogenase in the mitochondria generic 50mg tofranil otc anxiety symptoms in children checklist. Some studies have reported an increased frequency of the gene that encodes for alcohol dehydrogenase in patients with alcoholic liver disease buy tofranil 25mg on line anxiety symptoms mimic ms, leading to increased production of acetaldehyde. Alcoholics with decreased acetaldehyde dehydrogenase activity also develop alcoholic liver disease at a lower cumulative intake of alcohol than others. Alcohol has a direct hepatotoxic effect and does not require pre-existing malnutrition, but malnutrition may play a permissive role in producing alcohol hepatotoxicity. There is a threshold of alcohol toxicity beyond which no dietary supplements can offer protection. Obesity may also be an independent risk factor for the development of alcoholic liver disease. Finally, viral hepatitis, whether hepatitis B or hepatitis C infection, appears to play a role in the development of advanced alcoholic liver disease. Patients with alcoholic liver disease and viral hepatitis infection tend to develop their disease at a younger age, have more severe histological features and decreased survival. In addition, the presence of viral hepatitis is a major risk factor for the development of hepatocellular carcinoma in patients with alcoholic cirrhosis. Schematic representation of the progression of the different stages of alcoholic liver disease 3. Alcoholic Fatty Liver This is the most frequent hepatic abnormality found in alcoholics. It is a toxic manifestation of alcohol ingestion, appearing within three to seven days of excess alcohol intake. This results in the accumulation of triglyceride in the hepatocytes, mainly in the terminal hepatic venular zone. The fat may be macrovesicular (large droplets) or microvesicular (small droplets), which represents more active lipid synthesis by the hepatocytes. Fatty liver may occur alone or be part of the picture of alcoholic hepatitis or cirrhosis. Clinically, the patient is usually asymptomatic and examination reveals firm smooth hepatomegaly. Occasionally the fatty liver may be so severe that the patient is anorexic, nauseated and has right upper quadrant pain or discomfort. Attribution of fatty liver to alcohol use therefore requires a detailed and accurate patient history. In the case that the fatty liver is related to excess alcohol intake, this usually follows a prolonged heavy alcoholic binge. In the absence of a super-imposed hepatic process, stigmata of chronic liver disease such as spider angiomas, First Principles of Gastroenterology and Hepatology A. Liver biopsy is required to make a definitive diagnosis and to exclude the presence of steatohepatitis. When fatty liver is not associated with alcoholic hepatitis, the prognosis is excellent. Complete abstinence from alcohol and a nutritious diet will lead to disappearance of the fat over four to six weeks. Alcoholic Hepatitis Alcoholic hepatitis may occur separately or in combination with cirrhosis. This oxidative stress promotes hepatocyte necrosis and apoptosis, which is exaggerated in the alcoholic individual who is deficient in antioxidants such as glutathione and vitamin E. Free radicals then initiate lipid peroxidation, which causes inflammation and fibrosis. Inflammation is also incited by acetaldehyde that, when bound covalently to cellular proteins, forms adducts that are antigenic. Alcohol is known to cause an exaggerated gradient of hypoxia from the portal vein to the central vein, suggesting that the hypoxia induced by chronic alcohol use may also contribute to hepatic damage. Histologically, hepatocytes are swollen due to an increase in intracellular water secondary to increase in cytosolic proteins (Table 1). Polymorphs are seen surrounding Mallory containing cells and also within damaged hepatocytes. Neither fatty infiltration nor Mallory bodies are specific for alcoholic hepatitis nor are they necessary for diagnosis. It is maximal in zone 3 and extends in a perisinusoidal pattern to enclose hepatocytes, giving it a "chicken wiring" effect. Marked portal inflammation suggests an associated viral hepatitis such as hepatitis C, whereas fibrosis suggests complicating chronic hepatitis (Table 2). When the acute inflammation settles, a varying degree of fibrosis is seen which may eventually lead to cirrhosis. Histopathological changes of Alcoholic Hepatitis Perisinusoidalmaximal changes o Hepatocytesswollen (diffuse, pericentral changes) o Intrahepatocyte inclusionsMallory bodies o Fatmacrovesicular steotosis (zone 3) o Perihepatocyepolymorphs o Collagen (zone 3)perisinusoidal pattern to enclose hepatocytes (chicken wiring affect) Portalminimal changes First Principles of Gastroenterology and Hepatology A. Photomicrograph showing Mallory bodies (arrow) and inflammatory cells, especially polymorphs, in a patient with acute alcoholic hepatitis. Clinically, mild cases of alcoholic hepatitis are only recognized on liver biopsy in patients who present with a history of alcohol abuse and abnormal liver function tests. Hepatic decompensation can be precipitated by vomiting, diarrhea or intercurrent infection leading to encephalopathy. Gastrointestinal bleeding is common, due to the combination of a bleeding tendency and portal hypertension. Alcohol increases the patients susceptibility to liver damage by acetaminophen due to induction of the metabolizing enzymes and smaller doses of acetaminophen in an alcoholic may precipitate liver failure.
Other oral medication may be added to metformin or any first line drug used 25 mg tofranil visa anxiety symptoms related to menopause, if a single agent is not effective within 3-6 month tofranil 50mg anxiety symptoms sore throat. Insulin therapy is the final treatment when the oral medication discount 75 mg tofranil mastercard anxiety symptoms 3dp5dt, together with the lifestyle modifications, still do not help achieve a normal or desired HbA1c level, thus HbA1c < 7. The commonly used insulin is the long-acting insulin, which is mostly injected in the evenings and the short-acting insulin which is injected before meals. Usually metformin and other oral medication could still be continued even when insulin therapy is introduced or initiated (Terveyskirjasto 2015). It is important to constantly monitor weight, blood pressure and cholestrol levels after pharmacotherapy initiation, and also each time a drug is intensified (Diabetestietoa 2015a). Other oral antidiabetic agents and medication used in Finland besides metfor- min are sulphonylureas (glibenclamide, glipizide, glimepiride) to increase pancre- atic insulin secretion. Insulin sensitzers or glitazones (pioglita- zones) are used to sensitize tissues to the effects of insulin. Oral anti-diabetic agents / medications are initiated when starting pharmacotherapy. Any of these drugs could be used as a mono, dual and/or triple therapy, though metformin is usually the pre- ferred first line drug to use unless contraindicated. Each therapy initiated is moni- tored and evaluated every three months before moving on to or adding on another therapy or stopping some therapy. Insulin therapy is the last therapy initiated and/or intensified when the desired HbA1c level is not attained. The cost and benefit: risk ratio is taken into consideration when choosing a medication and inef- fective therapies are stopped. Upon the diagnosis of type 2 diabetes in both countries, patients are educated about the disease: how to deal with it or manage it with their activi- ties of daily living and how their care plan is going to progress. The care given is patient centred and the goals are to: safely lower blood glucose level suing phar- macological and non-pharmacological therapies, improve patient wellbeing, edu- cate patients, evaluate micro and macro-vascular complications and reduce cardi- ovascular and other possible long term risk associated with type 2 diabetes. They both also have similar care pathways in the treatment of type 2 diabetes, it begins with lifestyle modifications, with possible bariatric surgery if the patient is very overweight. Then initiation of pharmacotherapy, if lifestyle modification measures alone are not providing the desired result. These steps in the treatment of type 2 diabetes are known as glycaemic control algorithm. For example, it explains what treatment to begin with and when to 48(55) initiate it as well as the appropriate time for next step in the treatment. Glycaemic control algorithm care pathway always begins with lifestyle modification interven- tions (diet + exercise) for every type 2 diabetic patient. Oral anti-diabetic agents are then added to lifestyle modifications when the target level of blood glucose level is not achieved or maintained. Both countries have the same medication, such as metformin, and the time frame in the medication usage is also the same. All dual or combination therapies were more efficient than mono-therapies and reduced HbA1c levels by an addi- tional 1%. There was also greater decrease in HbA1c level when metformin was combined with other agents, for example metformin + sulphonyurea. The risk of hypoglycaemia is increased when increatin-based therapies are added to sulpho- nylurae, though they are generally well tolerated and have a low risk of hy- poglygaemia. Nutritional therapy should focus on the lifestyle modifications to result in increased energy figure through physical activity and lowered energy intake. The nutritional therapy of diabetes type 2 emphasis on lifestyle planning to reduce glycaemia, dyslipidaemia and blood pressure; because many people with diabetes have hypertension and dyslipidaemia. This leads to reduction in the in- take of cholesterol, saturated fat and sodium desirable. This planning should start as soon as the patient has been diagnosed with diabetes. An increase in physical activity can result in improved glycaemia, lowered insulin resistance, and reduced cardiovascular risk factors. The distribution of the food intake, three meals or smaller meals and snacks, should be based on individual preferences. Treatment with insulin therapy requires firmness in timing of meals and carbohydrate content. Untreated diabetes type 2 can lead to different kind of health problem such as heart disease and stroke, nerve damage, kidney disease and foot problem. This litera- ture review describes the treatment both pharmacology and nutritional treatment. The quantity of food patient eat depend on weight, diet, exercise regularity and other health risk. Physical activity monitoring is also done and encouraged by nurses and care giver need to make sure that both pa- tient and the family member are well counselled. Dietician role is important when a patient is diagnosed with type 2 diabetes, they provided tailor-made dietary plan, considering the lifestyle modifica- tion and any medical conditions. Education needs a multidisciplinary approach, with dieticians and practice nurses providing evidence-based local advice to both patients and carers about nutrition and food, along with supporting other health-care staff to maintain an accurate and 52(55) consistent message. Health professionals can help patient in plan- ning their exercise schedule and diet intake and record their behaviour including challenges and positive outcome. Enough time should be taken in other for care givers to notice the change in social, physical, psychological factors that add to patient exercise and diet behaviour. Both health-care professionals and patients must aware that changing diet and exercise behaviour require a gradual process. Patient who are constantly supported either by family or care givers to take charge in their weight loss and make lifestyle changes are likely to have an adequate long-term result. Nurses, Doctors, Dietician, Family member as well as pa- tient must work together to ensure good result after treatment.
This enzyme is attached to the capillary endothelium in tissues 75 mg tofranil with mastercard anxiety loss of appetite, such as the heart and adipose tissue order 75 mg tofranil with mastercard anxiety symptoms on dogs, that are active in utilizing fatty acids cheap 50mg tofranil overnight delivery anxiety symptoms 4 days. The released fatty acids are then taken up and utilized in the peripheral tissues. The process of lipolysis is extremely efficient, and the half-life of chylomicron triglyceride in the circulation is normally less than 15 minutes in the postabsorptive or interdigestive state. The substrates for triglyceride assembly include free fatty acids released from adipose tissue through the action of a hormone-sensitive lipase, and fatty acids synthesized in the liver from acetyl-CoA. There is a depletion of liver glycogen within 24 to 48 hours, with stimulation of gluconeogenic enzymes to allow the production of glucose from amino acids released through protein breakdown in skeletal muscle. Lipolysis in adipose tissue leads to increased fatty acid levels and activation of enzymes responsible for - oxidation of fatty acid in the liver (acyl-CoA-carnitine acyltransferase). One important adaptive response to starvation is the induction of 3-hydroxybutyrate dehydrogenase in the brain, which allows this organ to utilize ketone bodies as a fuel. Decreased dependence on glucose reduces the need for excess gluconeogenesis and spares muscle protein. In a relatively lean 70 kg man with 12% body fat, survival without food can be expected to be about 60 days or longer. Clinical and Laboratory Features of Protein- Energy Malnutrition Protein-energy malnutrition may result from a number of causes. Intake or assimilation may be impaired or, alternatively, losses may be increased, as occurs with excessive enteric protein loss in protein-losing enteropathies. Moreover, requirements may be significantly increased in some patients as a result of growth, pregnancy, tissue injury or a superimposed disease process. In some patients with chronic debilitating diseases, multiple factors may be responsible. Causes of protein-energy malnutrition Impaired intake o Insufficient quantity or quality o Impaired intake due to systemic disease (e. Shaffer 653 Malnutrition has been classically divided into kwashiorkor (protein restricted) and marasmus (protein-calorie restricted). In kwashiorkor, the subject ingests a moderate number of calories, usually as complex carbohydrate (e. The carbohydrate is absorbed as glucose, causing rises in plasma glucose and insulin, and leading to decreased lipolysis and proteolysis. The liver is therefore supplied with inadequate amino acids, with little oral intake and little peripheral mobilization from skeletal muscle stores. The low caloric intake means that only small amounts of carbohydrate are taken; plasma glucose and insulin are low. Hence, lipolysis and proteolysis occur, with adequate delivery of amino acids from muscle to the liver for protein production. Fatty liver does not occur, and serum albumin levels tend to be normal, with no peripheral edema. Often patients fall between these two extremes of nutritional states, but there are examples of kwashiorkor and marasmus in Western clinical practice. Marked muscle wasting and loss of subcutaneous tissue (adipose tissue) occur with normal-sized nonfatty livers and no peripheral edema. In contrast, the intensive care unit patient who has received intravenous dextrose (glucose) without amino acids for a prolonged period will often show a fatty liver and marked hypoalbuminemia and edema. Other changes in the liver that may occur in nutritional disorders are listed in Table 3. Effects of specific nutritional disorders on the liver Nutritional disorders Effects on the liver Common conditions o Alcoholism Steatosis, alcoholic hepatitis and cirrhosis o Obesity Steatosis, steatohepatitis and cholelithiasis o Uncontrolled Glycogenosis, steatosis and steatohepatitis diabetes o Protein deficiency Pigment stones o Kwashiorkor Steatosis and decreased protein synthesis o Fasting Mild unconjugated hyperbilirubinemia, especially in Gilberts syndrome Uncommon conditions o Jejunoileal bypass Steatosis and steatohepatitis o Gross dietary iron Bantu siderosis/hemochromatosis excess o Senecio alkaloids Veno-occlusive disease o Dietary aflatoxins Hepatocellular carcinoma (? Except for cheilosis and glossitis, which are seen with multiple vitamin B deficiencies, physical findings of vitamin deficiencies are seldom observed in protein-calorie malnourished patients in developed countries. Trace elements are elements that are required in small quantities (milligram amounts or less) for normal growth and/or function. Except for iron deficiency due to blood loss and/or poor intake, deficiency states of trace elements are rare in subjects with some oral intake, since only minute amounts are required. Effects of Malnutrition on the Gastrointestinal Tract and Pancreas Protein-energy malnutrition may produce major structural and functional changes in the gastrointestinal tract and pancreas, which, in turn, may aggravate the underlying poor nutritional condition. In severe protein-energy malnutrition, for example, acinar cell atrophy occurs and exocrine cells have decreased numbers of zymogen granules. Pancreatic secretion may be reduced following stimulation with cholecystokinin and/or secretin. With reversal of malnutrition these can return to normal levels, but this may require several weeks. In addition to pancreatic exocrine changes, the entire wall and mucosal lining of the stomach and intestine may be reduced in thickness. Microscopically, marked changes may develop, including severe flattening of the small intestinal mucosa, similar to celiac disease. In contrast to celiac disease, however, reduced numbers of crypt mitoses are seen. Changes may be present throughout the small intestine in an irregular patchy distribution, although the jejunum appears to be most severely affected. Altered uptake of glucose and D-xylose has also been reported, and steatorrhea may be present with impaired absorption of fat and some fat-soluble vitamins. In addition, there may be increased protein loss from the gut, leading to increased fecal nitrogen loss. Finally, specific nutrients may be deficient and cause alterations in certain tissues. In particular, folic acid and vitamin B12 deficiencies may lead to subtotal villous atrophy in association with crypt hypoplasia (Table 4).