CASES An 18 month old boy is brought to the emergency room by police for evaluation. He and his siblings were all removed from their home earlier in the day, after a neighbor's complaint. There are no Parents or guardians present to give a history, although the police officer comments that the mother is thought to be an injection drug user. The 12 year old sister, who seems to be the primary caregiver, is worried that the toddler is sick, stating that “he’s gotten really skinny" and he "keeps a cold," with constant rhinorrhea and cough. She is unsure if he has seen a doctor, but thinks that he "got all his baby shots". Diet history is revealing: meals are generally prepared by the 12 year old and 10 year old siblings, and consist of packaged macaroni and cheese, canned spaghetti or noodles, peanut butter and jelly sandwiches, and occasionally fast food drive-ins. The older kids usually drink juice and sodas, though the toddler also drinks some milk. On exam, the toddler is anxious, clinging to his older sister. He appears thin, with a large head and subcutaneous wasting. Vital signs are appropriate for age. Weight is 9 kg (<3rd percentile); height is 72 cm (<3rd percentile); head circumference is 47 cm (10th percentile). Exam is significant for subcutaneous wasting, sparse hair, dry skin, and a scaling rash in the diaper area. There are no overt signs of trauma, and no focal neurologic deficits. Laboratory evaluation is significant for a microcytic anemia and a decrease in serum albumin. The toddler is admitted to the hospital for protection, and monitoring during the refeeding process, which proceeds without incident. With concern for infectious risk factors, an HIV test is ordered - which 's positive. CD4 count is 1500. Antiretroviral therapy is instituted, with good immunologic response. With the provision of sufficient calories and protein in the diet, weight gain begins to improve. 1, Discuss malnutrition. What are the signs and symptoms of the patient that conforms to your diagnosis? ‘The World Health Organization (WHO) defines malnutrition as “the cellular imbalance between the supply of nutrients and energy and the body's demand for them to ensure growth, maintenance, and specific functions." The term protein-energy malnutrition (PEM) applies to @ group of related disorders that include marasmus, kwashiorkor, and intermediate states of marasmus-kwashiorkor. The term marasmus is derived from the Greek word marasmos, which means withering or wasting. Signs and symptoms seen from the patient that conforms protein energy malnutrition specifically kwashiorkor are subcutaneous wasting, sparse hair, dry skin, and a scaling rash in the diaper area which is brought about by almost increased carbohydrate diet and low protein intake that is stated in the case. 2. Elaborate on the pathophysiology of the signs and symptoms of malnutrition seen in this case. {In general, marasmus is an insufficient energy intake to match the body's requirements. As a result, the body draws on its own stores, resulting in emaciation. In kwashiorkor, adequate carbohydrate consumption and decreased protein intake lead to decreased synthesis of visceral proteins. The resulting hypoalbuminemia contributes to extravascular fluid accumulation. Impaired synthesis of B-lipoprotein produces a fatty liver. Protein-energy malnutrition also involves an inadequate intake of many essential nutrients. Low serum levels of zinc have been implicated as the cause of skin ulceration in the patient, Patients withx QUESTIONS 1, Explain the process of temperature regulation: ‘The temperature of the body is controlled almost entirely by the nervous feedback ‘mechanisms which operate through temperature-regulating centers located in the hypothalamus. ‘The anterior hypothalamic-preoptic area contains large numbers of heat-sensitive neurons as well as one-third as many cold-sensitive neurons which both function as temperature sensors. Heal sensitive neurons increase their activity in response to an increase in body temperature. Cold- sensitive neurons increase activity when the temperature falls. When the preoptic area in the hypothalamus is heated, the skin all over the body immediately sweats profusely while the skin blood vessels become greatly dilated. This brings body temperature to normal levels. Body temperature is maintained by balancing heat production and heat loss. When the rate of heat production in the body is greater than the rate at which heat is being lost, heat builds up in the body and the body temperature rises. Conversely, when heat loss is greater, both body heat and body temperature decrease. Heat production is the result of the body’s metabolism in order to maintain basic needs ‘and physical activities that we do. This heat produced from the different organs of the body is transferred to the skin where it is lost to the air and other surroundings. Blood flow to the skin provides heat transfer, In the mest exposed areas of the body, blood is supplied to the plexus directly from the small arteries through highly muscular arteriovenous anastomoses. A high rate of skin flow causes heat to be conducted from the core of the body to the skin with great ‘efficiency whereas reduction in the rate of skin flow can decrease the heat conduction from the core to very litle. The skin is an effective controlled “heat radiator” system and the flow of blood to the skin is a most effective mechanism for heat transfer from body core to the skin. 2. Define or describe the following: EVAPORATION, CONDUCTION, CONVECTION and DIAPHORESIS. Evaporation is the process by which liquid changes into gas. When water evaporates from the body surface heat is also lost. Even when a person is not sweating, water still evaporates insensibly from the skin and lungs. This causes continual heat Joss, This results from continual diffusion of water molecules through the skin and respiratory surfaces. Conduction is the direct transfer of heat from the body to solid objects which is about, 3%. Loss of heat by conduction to air is greater at about 15% under normal conditions. The vibratory motion of the molecules of the skin generates heat which can be transferred to the air if the airis colder than the skin. No further heat loss oceurs when the temperatures of both the skin and the air adjacent to the skin are equal. Convection is the removal of heat from the body by air currents. The heat is first, ‘conducted to the air and then carried away by the convection air currents, A small amount ofCASE2 1. Whatis inborn error of metabolism? What are the common affected biochemical pathways that manifest as metabolic disease? Inborn Errors of Metabolism (IEM) comprise a group of disorders in which a single gene defect Causes a clinically significant block in a metabolic pathway resulting either in accumulation of substrate behind the block or deficiency of the product. All IEMs are all genetically transmitted typically in an autosomal recessive or X-linked recessive fashion. In IEMs single gene defects are responsible for the abnormalities in the synthesis or catabolism of proteins, carbohydrates or fats by way of defective enzymes or transport proteins, resulting in a block of metabolic pathway. The male to female ratio is 1:1 for X-linked dominant if transmission Is from mother to child . Effects are due to toxic accumulations of the substrates before block, intermediates from alternative metabolic pathways, defects in energy production and use caused by a deficiency of products beyond the block or a combination of these metabolic deviations. Nearly every metabolic disease has several forms that vary in age of onset, clinical severity and often mode of inheritance. Proper history from parents has a role in suspecting IEM. Parental consanguinity increases the chance of autosomal recessive IEM. The major categories are: Categories of IEM are as follows: i. Disorders of protein metabolism (eg. Aminoacidopathies, Organic acidopathies, Urea cydedefects). ii. Disorder of carbohydrate metabolism (e.g Carbohydrate intolerance disorders, Glycogen Storage Disorders, iii, Disorders of Gluconeogenesis and Glycogenolysis) iv. Lysosomal storage disorders (e.g. Gaucher's disease, Niemann-Pick disease) ve Disorder of Lipid metabolism (e.g. Fatty acid Oxidation Defects [Medium Chain Acyl Dehydrogenease Deficiencyl, Sphingolipidoses) Mitochondrial disorders (e.g. Kearns-Sayre syndrome) Peroxisomal disorders (e.g. Zellweger syndrome, Adrenoleucodystrophy). Trace metal disorders ( Menke's kinky Hair syndrome, Wilson’s disease). Organic acidemias are caused by abnormal metabolism of proteins, fats or carbohydrates and are characterized by marked metabolic acidosis with ketosis, often with elevated lactate and mild to moderate hyperammonemia. Common signs include vomiting, signs of encephalopathy, neutropenia and thrombocytopenia. Fatty acid oxidation defects also known as Beta-oxidation defects, are a distinct type of organic acid disorder, characterized by hypoketotic hypoglycemia, hyperammonemia, and cardiomyopathy, and may present clinically with Reye's syndrome. Medium-chain acyl-CoA dehydrogenase deficiency (MCAD) is among the most common of all IEMs and may account for 5% of SIDS cases. Primary Lactic Acidoses present with severe lactic acidosis. Aminoacidopathies may have similar presentation to the organic acidemias, butare a very heterogeneous group of disorders. Hereditary tyrosinemia can present in the neonate with a bleeding diathesis due to liver disease, or later in infancy with a renal Fanconi syndrome. The severe form of nonketotic hyperglycinemia presents as unremitting3. ELABORATE ON THE PATHOPHYSIOLOGY OF MALIGNANT HYPERTHERMIA. WHAT ARE THE POSSIBLE CONSEQUENCES? Malignant hyperthermia (MH) is a subclinical myopathy that allows large quantities of calcium to be released from the sarcoplasmic reticulum (SR) of skeletal muscle and cause a hypermetabolic state after exposure to triggering agents, Altered calcium channel gating Kinetics In the SR is the undertving cause, The sustained elevation of calcium allows excessive stimulation of aerobic and anaerobic alycolytic metabolism, which accounts for respiratory and metabolic acidosis, rigidity, altered cell permeability, and hyperkalemia, When the ryanodine receptor is stimulated in skeletal muscle that is susceptible to MH or in skeletal muscle that is not susceptible to MH, calcium is released from the sarcoplasmic reticulum (through the ryanodine receptor) into the myoplasm, causing muscle contraction. During an anesthetic-induced MH reaction, excess quantities of calcium flood into the myoplasm, initiating muscle rigidity, increased heat production, and acidosis. Elevated myoplasmic Ca2+ stimulates phosphorylase kinase, leading to increased glycolysis resulting in lactic acid formation; initiates muscle contraction by binding to troponin; increases adenosine triphosphate (ATP) use through stimulation of myosin ATPase [adenosine {triphosphatase}; and causes mitochondria to sequester calcium in a process requiring ATP despite ATP depletion by other ongoing processes. The sarcolemmal membrane integrity can no longer be maintained and additional Ca2+ leaks into the muscle while Ck [creatine kinase], potassium, and myoglobin leak out. ‘The consequences of having malignant hyperthermia are: 1) the elevated myoglobin may damage the kidneys. Without adequate treatment, the process may progress to multiorgan failure and death; 2) large ischemic demands imposed by the hypermetabolic state prevailing during acute MH can severely impair myocardial function; 3) extreme temperature elevation, hyperkalemia, acidosis, and cerebral edema can affect the central nervous system (CNS), causing coma, areflexia, and dilated pupils. Activation of the sympathetic nervous system occurs early and red intravascular coagulation (DIC) can occur as a consequence of therelease of tissue thromboplastin. Pulmonary changes are secondary to systemic effects. Eventually, metabolic exhaustion ensues, leading to increased cellular permeability, whole-body edema, compartment syndrome in the extremities, cerebral edema, and death. 4. WHY DOES AN INCREASE IN MUSCLE ACTIVITY LEAD TO HYPERTHERMIA? WHY DOES IT LEAD ‘TO LACTIC ACIDOSIS? Increase in muscle activity leads to hyperthermia because the body is metabolizing the primary sources of energy such as the carbohydrates, fats, and protein in order to form ATP which is important and the energy of the cell in order for the body to do such activities. When there is increased in activity the body will also produce more ATP to provide adequate energy of the body, Lactic acid is a by-product of anaerobic metabolism in which the body does not need oxygen to produce energy. In increased muscle activityREFERENCE: Leleiko NS, Chao C. Nutritional Deficiency States. In: Rudolph AM, et al (eds). Rudolph's Pediatrics, 20th edition. 1996, Stamford, CT: Appleton and Lange, pp. 1015-1017. Williams, Cicely (1935). "Kwashiorkor". The Lancet 226 (5855): 1151-1152. doi:10.1016/S0140-6736(00)94666-X. World Health Organization; UNICEF; UN System Standing Committee on Nutrition (2006) WHO, UNICEF, and SCN informal consultation on community-based management of severe malnutrition in children ~ SCN Nutrition Policy Paper No. 21. Available at:hitp://www.who.int/child_adolescent_health/documents/fnb_v27n3_suppV/en/index html Case 4. Obesity A 45 year old man had been willing to slim down for several years. He was consulted by many therapists, and various diets were recommended for him. Unfortunately nothing helped out. And several days ago he decided to start starving and to get rid of several kilos. Therefore he sought consult about the new diet, which lacks carbohydrate but rich in fat. It has turned out that this man has been having overweight since he was 15 or 16 years old. As he grew up he always had not less than 100 kilograms. His father and his brother were also obese. At the moment this man weighs 108 kilograms, and is 178 cm tall. The majority of fat are allocated in the belly area. The concentration of blood glucose is at the normal level. 1, Discuss the criteria in defining obesity. List possible causes of obesity For adults, overweight and obesity ranges are determined by using weight and height to calculate a number called the Body Mass Index. This can be calculated by the formula: Wieight in BM] = Wisight nko * Height in sq.m The results can be interpreted as: BMI Interpretation <185 Underweight 185-249 | Healthy Weight 25,0-29.9 _| Overweight 300r higher_| Obese In clinical terms, a BMI between 25 and 29.9 kg/m2 is called overweight, and a BMI greater than 30 kg/m2 is called obese. BMI is not a direct estimate of adiposity and does not take into account the fact that some individuals have a high BMI due to a large muscle mass. A better way to define obesity is to actually measure the percentage of total body fat. Obesity is usually defined as 25% or greater total body fat in men and 35% or greater in women. Other methods8. What are BROWN fats? What is its importance to thermogenesis? Brown fats are a type of adipose tissue with multiple globules filled with numerous mitochondria which serve as conductors of heat in contrast to White adipose tissue which has only one globule and acts for lipid storage. Brown fats contribute in a special type of heat production called nonshivering thermogenesis, Shivers are response of the body to adjust to a sudden drop in environmental temperature to produce heat much like chills. In nonshivering thermogenesis, heat is produced through the sympathetic nervous system in which catecholamines such as epinephrine and norepinephrine are released to accelerate metabolism and heat production. The mitochondria in brown fats undergo oxidative phosphorylation but instead of producing ATP, heat is generated because the reaction is uncoupled. Brown fats are more common in infants especially those still developing inside the womb compared to adults who have @ majority of white adipose tissue (Guyton, 2006). REFERENCES: Guyton, A. C., Hall, J.E. 2006. Textbook of Medical Physiology. 11 edition. pp. 887,889-894, 899, Pennsylvania: Elsevier Saunders Marcoviteh, H. 2005.Black's Medical Dictionary. 41* edition. pp. 270-271. London: A & C Black Publishers Limited Chills, 2013. Jn MedlinePlus. Retrieved from https://www.nlm.nih, gov/medlineplus/ency/article/003091.htm Crouch and Meurier, Health Assessment, Retrieved from hitps://oooks.google.com/books?id=9TNiCgAAQBAJ&pg=PT1978:dq=modes+of+monitoring+b ody+temperature&hl=en&sa=X& ved=OahUKEwjphaGV_rXKAhWHnSQKHXcfA- 8Q6AEUTAA#v=onepageaeq=modes%2001%20monitoring%20body%20temperature&f=false Potter et al (2015).Essentials for Nursing Practice 8" edition. (p 273). Retrieved from htps://books. google.com. ph/books?id=obPwAWAA QBAJ&pg=PA273 &dq=diaphoresis+forthea tHoss&hi-end&sa=X&rved=OahUKE vj Yksy20LjKABXFN6YKHReIB WY Q6AEIjAC#=onepag e&q=diaphoresis%20for%20heat% 20loss&effalsethe muscle cannot have time to have aerobic metabolism so to produce such energy it undergoes anaerobic metabolism which then form lactic acid as a by-product of ‘metabolism and accumulation of this lactic acid in the body will cause lactic acidosis. 5. ABREAKTHROUGH IN THE ACUTE TREATMENT OF MALIGNANT HYPERTHERMIA OCCURRED WITH THE DISCOVERY OF DANTROLENE (WITH THE CONCOMITANT CESSATION OF ANESTHESIA). INVESTIGATE THE ACTIONS OF DANTROLENE AND COME UP WITH A POSSIBLE EXPLANATION OF ITS LIFE SAVING ACTION. Dantrolene is a hydantoin derivative that directly interferes with muscle contraction by ‘the RR receptor. Dantrolene interferes with calcium release within skeletal muscle cells (from sarcoplasmic reticulum). Dantrolene inhibits calcium lon release from the ‘sarcoplasmic reticulum so the effect is there will be no activator for muscle contraction ‘thus Inhibiting muscle activities and decreasing also the body temperature of a person. ‘CASE 2 INBORN ERRORS OF METABOUSM, ‘A2 day old infant was referred for persistent hypotonia and mild respiratory distress since birth, He also had feeding Intolerance characterized by emesis following each feeding. He is the product of a full term Pregnancy to a 26 year old G1P1 Ab0, 0+, Hepatitis B negative, rubella immune mother via NSVD with APGAR scores of 7 and 8 at 1 minute and 5 minutes, respectively. The baby nursed overnight without any difficulty, and was able to pass his first meconium at less than 24 hours old. However, his first breastfeeding was followed by emesis. A second feeding of water also resulted in emesis. Due to the persistent hypotonia, feeding intolerance, and continued mild respiratory distress despite adequate oxygenation, the infant was transferred to a tertiary care neonatal intensive care unit. Examination: Temperature 36.5; PR 136/min; RR 44/min, BP 58/41, Oxygen saturation: 100% in room air. Wt: 3.95 kg (80 percentile). He is a term-appearing male infant who is noted to be slightly tachypneic and intermittently grunting. His head, ears, eyes, nose and oropharyngeal structures are without obvious abnormalities, except for his tongue which is remarkable for lateral fasciculations, His neck is supple. His lungs are clear, but he has notable intermittent grunting. His heart is regular with no murmurs, His abdomen is flat and soft, but his liver is palpable 2.cm below right subcostal margin. His extremities are normal, with 1+ pulses. His DTRs are absent. Genitalia are normal. He is hypotonic with poor head control, A full sepsis workup is done and he Is started on empiric antibiotics. An ABG demonstrates a severe metabolic acidosis with pH 7.22 and Bicarbonate 10. Anion gap is 23. Lactic acid and ammonia levels are elevated. After consultation with genetics, it is felt that the infant likely has a defect in energy ‘metabolism based on the persistent hypotonia and severe acidosis. ‘A metabolic defect workup is done, including urine for organic acids, plasma for amino acids, and muscle biopsy for fibroblast culture and electron microscopy analysis. He is started empirically ona vitamin cocktail consisting of thiamine, niacin, riboflavin, B12, biotin, and L-carnitine for the possibility of a fatty acid oxidation or mitochondrial defect. An MRI on day 3 of life reveals severe cerebral atrophy and developmental brain anomalies including agenesis of the corpus callosum. He later decompensatedless than 35 kg/m2) to achieve a weight loss of approximately 1 pound each week. A more aggressive energy deficit of $00 to 1000 kilocalories per day is recommended for persons with BMIs greater than 35 kg/m2. Typically, such an energy deficit, if it can be achieved and sustained, will cause a weight loss of about 1 to 2 pounds per week, or about a 10 per cent weight loss after 6 months. For most people attempting to lose weight, increasing physical activity is also an important component of successful long-term weight loss. Also, it is important to prevent vitamin deficiencies during the dieting period. Various drugs for decreasing the degree of hunger have been used in the treatment of obesity. The most widely used drugs are amphetamines (or amphetamine derivatives), which directly inhibit the feeding centers in the brain. One drug for treating obesity is sibutramine, a sympathomimetic that reduces food intake and increases energy expenditure. The danger in using these drugs is that they simultaneously overexcite the central nervous system, making the person nervous and elevating the blood pressure.Also, a person soon adapts to the drug, so that weight reduction is usually no greater than 5 to 10 per cent. Another group of drugs works by altering lipid metabolism. For example, orlistat, a lipase inhibitor, reduces the intestinal digestion of fat. This causes a portion of the ingested fat to be lost in the feces and therefore reduces energy absorption. However, fecal fat loss may cause unpleasant gastrointestinal side effects, as well as loss of fat-soluble vitamins in the feces. For morbidly obese patients with BMIs greater than 40, or for patients with BMIs greater than 35 and conditions such as hypertension or type II diabetes that predispose them to other serious diseases, various surgical procedures can be used to decrease the fat mass of the body or to decrease the amount of food that can be eaten at each meal. Two of the most common surgical procedures used in the United States to treat morbid obesity are gastric bypass surgery and gastric banding surgery. Gastric bypass surgery involves construction of a small pouch in the proximal part of the stomach that is then connected to the jejunum with a section of small bowel of varying lengths; the pouch is separated from the remaining part of the stomach with staples. Gastric banding surgery involves placing an adjustable band around the stomach near its upper end; this also creates a small stomach pouch that restricts the amount of food that can be eaten at each meal. Although these surgical procedures generally produce substantial weight loss in obese patients, they are major operations, and their long-term effects on overall health and mortality are still uncertain. Sources’ Guyton, A.C & Hall, JE. (2006). Textbook of Medical Physiology. 1 Ith ed. Elsevier Inc. USA. Hill et. al (2012). Energy Balance and Obesity. Retrieved January 24, 2016 from hup://circ.ahajournals.org/content/126/1/126.full.lower than 40g/L and albumin is lower than 35 g/L. In kwashiorkor, plasma cortisol and growth hormone levels are high, but insulin levels are decreased. Body water is increased and albumin level is 10-25¢/L. 4. What vitamin deficiencies are manifested in this patient? Vitamin B3 (Niacin or nicotinic acid and its derivatives), is endogenously synthesized from tryptophan, and exogenously derived from grains, legumes, seed oils, and meats. It is a component of NAD and NADP, and acts as a coenzyme for dehydrogenation reactions, especially those in the hexose ‘monophosphate shunt, in glucose metabolism. Populations at particular risk for niacin deficiency include those with with protein-deficient diets. Severe deficiency, cause symptoms related to the skin, digestive system, and nervous system. They includes scaly pigmented rash as seen in patient. Vitamin C deficiency can contribute to iron deficiency anemia by causing capillary fragility, hemolysis, and bleedi ymin C or ascorbic acid, is found in milk, liver, fish, fruits, and vegetables. It is involved in the activation of prolyl and lysyl hydroxylases from inactive precursors, therefore facilitating the hydroxylation of procollagen. Populations at particular risk for vitamin C include those with marginal or erratic diets (the classic example is of malnourished sailors without fresh vegetables), dialysis patients, or infants on processed milk only. The clinical spectrum of vitamin C deficiency encompasses bone disease (in growing children), hemorrhagic disease (skin, mucosal, and subperiosteal bleeds, bleeds into joint spaces), impaired wound healing, and anemia as manifested by the patient.lower than 40g/L and albumin is lower than 35 g/L. In kwashiorkor, plasma cortisol and growth hormone levels are high, but insulin levels are decreased. Body water is increased and albumin level is 10-25¢/L. 4. What vitamin deficiencies are manifested in this patient? Vitamin B3 (Niacin or nicotinic acid and its derivatives), is endogenously synthesized from tryptophan, and exogenously derived from grains, legumes, seed oils, and meats. It is a component of NAD and NADP, and acts as a coenzyme for dehydrogenation reactions, especially those in the hexose ‘monophosphate shunt, in glucose metabolism. Populations at particular risk for niacin deficiency include those with with protein-deficient diets. Severe deficiency, cause symptoms related to the skin, digestive system, and nervous system. They includes scaly pigmented rash as seen in patient. Vitamin C deficiency can contribute to iron deficiency anemia by causing capillary fragility, hemolysis, and bleedi ymin C or ascorbic acid, is found in milk, liver, fish, fruits, and vegetables. It is involved in the activation of prolyl and lysyl hydroxylases from inactive precursors, therefore facilitating the hydroxylation of procollagen. Populations at particular risk for vitamin C include those with marginal or erratic diets (the classic example is of malnourished sailors without fresh vegetables), dialysis patients, or infants on processed milk only. The clinical spectrum of vitamin C deficiency encompasses bone disease (in growing children), hemorrhagic disease (skin, mucosal, and subperiosteal bleeds, bleeds into joint spaces), impaired wound healing, and anemia as manifested by the patient.such as measuring skin fold thickness, bioelecirical impedance, or underwater weighing, are also used but not as common as BMI. The following are possible causes of obesity: a. Greater energy intake than energy expenditure - When greater quantities of energy (in the form of food) enter the body than are expended, the body weight increases, and most of the excess energy is stored as fat. Therefore, excessive adiposity (obesity) is caused by energy intake in excess of energy output. For each 9.3 Calories of excess energy that enter the body, approximately 1 gram of fat is stored. b, Sedentary Lifestyle — is the major cause of obesity. Inadequate physical activity is typically associated with decreased muscle mass and increased adiposity. For example, studies have shown a close association between sedentary behaviors, such as prolonged television watching, and obesity. c. Abnormal Feeding Behavior — causes excessive energy intake. This can be influenced by environmental, social and psychological factors. Stressful situations such as death of parents, severe illness and mental depression can influence a person to consume huge amounts of food as a means to release tension. Also, it has been suggested that overnutrition of children—especially in infancy and, to a lesser extent, during the later years of childhood—can lead to a lifetime of obesity. d. Neurologic Abnormalities - Lesions in the ventromedial nuclei of the hypothalamus cause an animal to eat excessively and become obese. Persons with hypophyseal tumors that encroach on the hypothalamus progressively develop obesity. Hence, it is possible that the functional organization of the hypothalamus or other neurogenic feeding centers in obese individuals is different from that of non-obese individuals. Studies in experimental animals also indicate that when food intake is restricted in obese animals, there are marked neurotransmitter changes in the hypothalamus that greatly increase hunger and oppose weight loss. ©. Genetic Factors ~ Obesity definitely runs in families yet it has been difficult to determine the precise roles of genetics in obesity. 20-25% of cases of obesity may be caused by genetic factors, 2, What mechanisms are responsible for the overweight of this man? At an individual level, a combination of excessive food energy intake and a lack of physical activity are thought to explain most cases of obesity. A limited number of cases are primarily due to genetics, medical reasons, or psychiatric illness. In contrast, increasing rates of obesity at a societal level are felt to be due to an easily accessible and palatable diet, increased reliance on cars, and mechanized manufacturing Genetics and environmental factors interplay in causing obesity. Polymorphisms in various genes controlling appetite and metabolism predispose to obesity when sufficient food energy is present. As of 2006, more than 41 of these sites on the human genome have beenlinked to the development of obesity when a favorable environment is present. People with two copies of the FTO gene (fat mass and obesity associated gene) have been found on average to weigh 3.4 kg more and have a 1.67-fold greater risk of obesity compared with those without the risk allele. Genes can contribute to obesity by causing abnormalities of (1) one or more of the pathways that regulate the feeding centers and (2) energy expenditure and fat storage. Three of the monogenic (single-gene) causes of obesity are (1) mutations of MCR-4, the most common monogenic form of obesity discovered thus far; (2) congenital leptin deficiency caused by mutations of the leptin gene, which are very rare; and (3) mutations of the leptin receptor, also very rare. All these monogenic forms of obesity account for only a very small percentage of obesity. It is likely that many gene variations interact with environmental factors to influence the amount and distribution of body fat. While genetics influences are important to understanding obesity, they cannot explain the current dramatic increase seen within specific countries or globally. The correlation between social class and BMI varies globally. A review in 1989 found that in developed countries women of a high social class were less likely to be obese. No significant differences were seen among men of different social classes. In the developing world, women, men, and children from high social classes had greater rates of obesity. The decrease in strength of correlation was felt to be due to the effects of globalization. Among developed countries, levels of adult obesity, and percentage of teenage children who are overweight, are correlated with income inequality. A similar relationship is seen among US states: more adults, even in higher social classes, are obese in more unequal states. Many explanations have been put forth for associations between BMI and social class. It is thought that in developed countries, the wealthy are able to afford more nutritious food, they are under greater social pressure to remain slim, and have more opportunities along with greater expectations for physical fitness. In undeveloped countries the ability to afford food, high energy expenditure with physical labor, and cultural values favoring a larger body size are believed to contribute to the observed patterns. Attitudes toward body weight held by people in one's life may also play a role in obesity. A correlation in BMI changes over time has been found among friends, siblings, and spouses. Stress and perceived low social status appear to increase risk of obesity, In the United States the number of children a person has is related to their risk of obesity. A woman's risk increases by 7% per child, while a man’s risk increases by 4% per child. This could be partly explained by the fact that having dependent children decreases physical activity in Western parents. 3. What could you propose as possible treatment of this man? Treatment of obesity depends on decreasing energy input below energy expenditure and creating a sustained negative energy balance until the desired weight loss is achieved. The current National Institutes of Health (NIH) guidelines recommend a decrease in caloric intake of 500 kilocalories per day for overweight and moderately obese persons (BMI greater than 25 butPHYSIOLOGY LABORATORY: MODULE 1 CASE 1: MALIGNANT HYPERTHERMIA QUESTIONS: 1. What is Malignant Hyperthermia? Malignant hyperthermia is a severe reaction to particular drugs that are often used during surgery and other invasive procedures, Specifically, this reaction occurs in response to some anesthetic gases, which are used to block the sensation of pain, and with a muscle relaxant that is used to temporarily paralyze a person during a surgical procedure. If given these drugs, people at risk for malignant hyperthermia may experience muscle rigidity, breakdown of muscle fibers (thabdomyolysis), a high fever, increased acid levels in the blood and other tissues (acidosis), and a rapid heart rate. Without prompt treatment, the complications of malignant hyperthermia can be life-threatening. 2. Discuss the etiology of malignant hyperthermia? MH is inherited as an autosomal dominant trait with reduced penetrance. It is associated with mutations in two genes: RYR/, which encodes the skeletal muscle isoform of the calcium-release channel of the sarcoplasmic reticulum (ryanodine receptor type 1 [RYR-1]) and CACNAIS, which encodes the alpha subunit of the L-type calcium channel isoform of the sarcolemma (dihydropyridine receptor). An aberrant termination of RYR-1 activity is found in MH- susceptible persons. RYR1 is located on chromosome 19. Mutations in this gene occur in at least 50% of persons with MH and all families of central core disease. In persons susceptible to MH, the ryanodine receptor in skeletal muscle is abnormal, and this abnormality interferes with regulation of calcium in the muscle. An abnormal ryanodine receptor that controls calcium release causes a buildup of calcium in skeletal muscle, resuiting in a massive metabolic reaction. This hypermetabolism causes increased carbon dioxide production, metabolic and respiratory acidosis, accelerated oxygen consumption, heat production, activation of the sympathetic nervous system, hyperkalemia, disseminated intravascular coagulation (DIC), and multiple organ dysfunction and failure. Early clinical signs of MH include an increase in end-tidal carbon dioxide (even with increasing minute ventilation), tachycardia, muscle rigidity, tachypnea, and hyperkalemia, Later signs include fever, myoglobinuria, and multiple organ failure. Anesthetics are inconsistent in triggering MH. A susceptible individual may undergo anesthesia with MH-triggering agents on multiple occasions without incident but may still react to such agents on a subsequent occasion. A history of uneventful anesthesia with MH-triggering agents does not rule out susceptibility to MH. In fact, there are reports of MH episodes occurring even with the use of supposedly safe agents.overweight of the patientis genetic factors. Obesity definitely runs in families. Yet it has been difficult todetermine the precise role of genetics in contributing to obesity because family members generally share many of the same cating habits and physical activity patterns. Genes can Contribute to obesity by causirig abnormalities of (1) one or more of the pathways that regulate the feeding centers and (2) energy escmers and fat storage. Three of the monogenic (single-gene) causes of obesity are (1) mutations of MCR-4 , the most common monogenic form of obesity discovered thus far; (2) congenital leptin deficiency caused by mutations of the Jeptin gene, which are very rare; and (3) mutations of the leptin receptor , also very rare. All these monogenic forms of obesity account for only a very small percentage of obesity. It is likely that many gene variations interact with environmental factors to influence the amount and distribution of bady fat. 3. What could you propose as a possible treatment for this man? years old and his father and his brother were also obese, a possible fk responsible for the ‘Treatinent of obesity depends on decreasing energy input below energy expenditure and creating a sustained negative energy balance until the desired weight lossis achieved. In other words, this means either reducing energy intake or increasing energy expenditure. Significant weight loss can be achieved in many obese persons with increased physical activity. The more exercise one gets, the greater the daily energy expenditure and the more rapidly the obesity disappears. Therefore, forced exercise is often an essential part of treatment. The current clinical guidelines for the treatment of obesity recommend that the first step be lifestyle modifications that include increased physical activity combined witha reduction in caloric intake. CASES A 30 year old female teacher decided to enroll in a gym class after consulting her doctor for an increase on her weight. History was unremarkable, physical examination was essentially normal and laboratory tests were within normal limits. Finally she started with aerobic exercises 3-4 time as week, Questions: 1. Explain the physiologic mechanisms for an increase in heart rate, ventricular contractility and cardiac output during such activities as aerobic exercise. What is the effect on blood pressure and why? At the onset of exercise, signals are transmitted not only from the brain to the muscles to cause muscle contraction but also into the vasomotor center to initiate mass sympathetic discharge throughout the body. Simultaneously, the parasympathetic signals to the heart are attenuated. ‘The heart is stimulated to greatly increased heart rate and increased pumping strength as a result of the sympathetic drive to the heart plus release of the heart from normal parasympathetic inhibition. One of the most important effects of increased sympathetic stimulation in exercise is to increase the arterial pressure. This results from multiple stimulatory effects, including (1) vasoconstriction of the arterioles and small arteries in most tissues of the body except the active muscles, (2) increased pumping activity by the heart, and (3) a great increase in mean systemic filling pressure caused 13mainly by venous contraction. These effects, working together, virtually always increase the arterial pressure during exercise. Many different physiologic effects occur at the same time during exercise to increase cardiac output approximately in proportion to the degree of exercise. In fact, the ability of the circulatory system to provide increased cardiac output for delivery of oxygen and other nutrients to the muscles during exercise is equally as important as the strength of the muscles themselves in setting the limit for continued muscle work, In general, mean arterial pressure rises during exercise as a result of the increase in cardiac output. However, the effect of enhanced cardiac output is offset by an overall decrease in TPR, and therefore mean blood pressure increases only slightly. Vasoconstriction in the inactive vascular beds helps maintain normal arterial blood pressure for adequate perfusion of the active tissues. The actual mean arterial pressure attained during exercise thus represents a balance between cardiac output and TPR. Systolic pressure usually increases more than diastolic pressure, which resultsin an increase in pulse pressure. The larger pulse pressure is primarily attributable to a greater stroke volume, but also to more rapid ejection of blood by the left ventricle and diminished peripheral runoff during the brief ventricular ejection period. (Hall & Guyton, 2011) 2. Explain the effect of aerobic exercise in blood flow on the following organs: a. Gut, kidney and non exercising muscles When cardiac stimulation occurs, the sympathetic nervous system also changes vascular resistance in the periphery. Sympathetic mediated vasoconstriction increases vascular resistance and thereby diverts blood away from the skin, kidneys, splanchnic regions, and inactive muscle. This increased vascular resistance persists throughout the period of exercise. (Koeppen, 2010) b. Skin Skin blood flow initially decreases during exercise, and then it increases as body temperature rises with increments in the duration and intensity of exercise. Skin blood flow finally decreases when the skin vessels constrict as total body 02 consumption nears its maximal value (Koeppen, 2010). Heart Blood flow to the myocardium increases. (Koeppen, 2010) d. Brain Blood flow to the brain is unchanged. (Koeppen, 2010) 3. Explain the decrease in blood volume during such activities. In humans, blood reservoirs do not contribute much to the circulating blood volume. In fact, blood Volumes usually reduced slightly during exercise, as evidenced by arise in the hematocrit ratio. This decrease in blood volume is caused by water loss externally through sweating and enhanced ventilation and by fluid movement into the contracting muscle. (Koeppen, 2010) 4. Describe the effect of moderate aerobic exercise on the following: a, PaO2 and PaCO2: very near to normal because the blood gases do not always have to become abnormal for respiration to be stimulated in exercise. Instead, respiration is stimulated mainly by neurogenic mechanisms during exercise. (Koeppen, 2010) 14> Tyrosinemia Type t-liver cirrhosis, peripheral neuropathy, renal tubular disorders, hydroxylase polyneuropathy, episodes of intense abdominal pain. 3. What is New Born Screen? Discuss the metabolic diseases detected by newbom screen. Newbom Screening (NBS) is a simple procedure to find out if a baby has a congenital metabolic disorder that may lead to mental retardation or even death if left untreated. Its ideally done immediately after 24 hours from birth. A few drops of blood are taken from the baby's heel, blotted ona special absorbent filter card and then sent to Newborn Screening Center (NSC). The blood sample for NBS may be collected by any of the following: physician, nurse, medical technologist, or trained midwife. Results can be claimed from the health facility where NBS was availed. Normal NBS Results are available by 7- 14 working days from the time samples are received at the NSC. Positive NBS results are relayed to the parents immediately by the health facility. Please ensure that the address and phone number you will provide to the health facility are correct. A NEGATIVE SCREEN MEANS THAT THE NBS RESULT IS NORMALLA positive screen means that the newborn must be brought back to his/her health practitioner for further testing. Babies with positive results must be referred at once to a specialist for confirmatory testing and further management. Should there be no specialist in the area, the NBS secretariat office will assist its attending physician. Newborn screening program in the Philippines currently includes screening of six disorders: ‘congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH), phenylketonuria (PKU), glucose- 6- phosphate dehydrogenase (G6PD) deficiency, galactosemia (GAL) and maple syrup urine disease (sup) Congenital Hypothyroidism (CH) - A lack of thyroid hormone that can cause mental and physical retardation if the hormone is not replenished. If the disorder is not detected and hormone replacement is not initiated within two weeks, the baby with CH may suffer from growth and mental retardation. Itis a partial or complete loss of function of the thyroid gland (hypothyroidism) that affects infants from birth (congenital). The thyroid gland produces iodine-containing hormones that play an important role in regulating growth, brain development, and metabolism. People with congenital hypothyroidism have lower-than-normal levels of these important hormones. Congenital hypothyroidism occurs when the thyroid gland fails to develop or function properly. Congenital Adrenal Hyperplasia (CAH) - The adrenals control salt balance and male hormones in the body. In CAH, too much hormone secretion from the adrenal glands can cause life threatening problems with salt balance in the body. It causes severe salt loss, dehydration and abnormally high levels of male sex hormones in both boys and girls. if not detected and treated early, babies with CAH may die within 7-14 days. People with congenital adrenal hyperplasia lack an enzyme needed by the adrenal gland to make the hormones cortisol and aldosterone. Without these hormones, the body produces more androgen, a type of male sex hormone. This causes male characteristics to appear early (or inappropriately). Galactosemia (GAL) - Galactose is a type of basic sugar. In fact, milk which has lactose sugars uses lactose enzymes to break it down into glucose and galactose. In galactosemia, galactose cannot beMaple Syrup Urine Disease == Death Alive ahd normal: 4. Discuss Importance NBS(new born screening) ‘One important goal of NBS is to try to offer early diagnosis to babies who have one of the diseases for which screening is available. Early diagnosis means treatment can be started as soon as possible. Early diagnosis and treatment can make a difference with health outcomes for these babies. It prevents life threatening and developmentally devastating outcomes. Most of the disorders that are detected are initially chemical problems in the body that, at first, don't have physical manifestations. It is difficult to diagnose these conditions early just by physical exam, so physicians have to rely on the blodd tests done with a newborn screen.A group of metabolic disorders related to the urea cycle defects are organic acidemias. These are caused by defective processing of the amino acids resulting in accumulation of organic acid byproducts or lack of production of a necessary end product. The symptoms are very similar to urea cycle defects; however, there are subtle laboratory differences. While urea cycle disorders result in hyperammonemia without acidosis and only occasionally hypoglycemia, the organic acidemias (as the name suggests) result in metabolic acidosis and hyperammonemia that is more on the order of 200-900 umol/L. One of the best understood diseases from this class of metabolic diseases is Maple Syrup Urine Disease (MSUD). MSUD occurs in the immediate neonatal period, presenting with acute decompensation within the first 2 weeks of life. Symptoms include lethargy, poor feeding, vomiting, and seizures, which eventually lead to coma and cerebral edema. Laboratory evaluation yields hypoglycemia, hyperammonemia (to a lesser degree than in urea cycle defects), acidosis, and ketosis. The urine from these patients has a striking odor of maple syrup. Lens dstocaton, seizures, Suffte oxdase deficiency. Facial ¢ysmorphi, congenital 3.0 -tsobutyic CoA deacylase aefeency, ‘Nonketotic Hyperglycinemia- Glycine cleavage system -Hypoglycemia, hypotonia, coma, poor feeding, lethargy, hyperammonemia, Fanconi-Bickel syndrome -Reabsorption defect Hepatomegaly, nephromegaly, dyslipidemia, rickets, glucose and Galactose intolerance. Maple Syrup urine disease -Body fluid odor that resembles maple syrup, vomiting, lethargy, seizures, coma. 3-Hydroxy-3-Methylglutaric aciduria -Vorniting, dehydration, hypoglycemia, metabolic acidosis, lethargy, coma, convulsions, delayed milestones. Asparty! glucosaminuria -Progressive psychomotor retardation, coarse facial features and mild osseous abnormalities. > Primary Carnitine deficiency-tncephalopathy, hepatomegaly, skeletal myopathy, apnea, hyperammonemia, developmental delay, nonspecific abnormal problems, Hypoglycemia and Cardiomyopathy. vvwyyconvection almost always occurs around the body because of the tendency for air adjacent to the skin to rise as it becomes heated, ‘Through perspiration or sweating the body promotes additional evaporative heat loss, Diaphoresis (i.e excessive sweating) drastically lowers body temperature and typically presents on the forehead, upper chest and arms. 3. Give the formula for the conversion of Farenheit to Celsius and Celsius to Farenheit. °C x 95 +32=°F (CF = 32) x 5/9=°C 4. Enumerate the different modes of monitoring temperature, Describe each and give its advantages and disadvantages ‘Oral ‘Comfortabl ‘Accuracy depends on site in oral cavity thermometer is placed in the oral Easily accessible ‘Affected by mouth breathing, food cavity (Posterior sublingual sites intake, smoking are best) for temperature Unsuitable for confused young children measurements and patients prone to seizures Temporal Quick to use Erroneously low results due to poor ‘Temporal artery thermometer is ‘operator technique and lack of cleaning used for monitoring core body thermometers temperature. itis held over the forehead and senses infrared emissions radiating from the skin axillary Least invasive Poorly reflect core body temperature ‘Temperature is measured at the because itis not close to any major axilla by placing the thermometer blood vessels and exposure to in the central position and environmental temperature and adducting the arm close to the chest perspiration wall ‘Tympanic Safety, speed Accuracy is affected by operator ‘Tympanic device is inserted into Correlate well with core body technique, size of ear canal and the ear canal. A probe picks up the temperature metabolic occurrences Infrared radiation emitted from the tympanic membrane Rectal Most accurate Uncomfortable Used only as last resort Time-consuming ‘Thermometer tip gently inserted through anus into rectum 0.5 to 1 inch depth Palpation Sensitive Not specificseizures with hypotonia and hiccoughs. MSUD classically presents at the end of the first week of feeding difficulties, lethargy, coma, seizures and the characteristic odor. with Urea cycle defects (e.g., citrullinemia, ornithine transcarbamylase deficiency, and arginosuccinic aciduria) result from the inability to detoxify nitrogen and are characterized by severe hyperammonemia and respiratory alkalosis, with a typical onset after 24 hours of age. Disorders of carbohydrate metabolism (e.g., galactosemia, hereditary fructose intolerance, fructose 1,6-diphosphatase deficiency and the glycogen storage diseases) are a heterogeneous group caused by inability to metabolize specific sugars, aberrant glycogen synthesis, or disorders of sluconeogenesis. They may manifest with hypoglycemia, hepatosplenomegaly, lactic acidosis or ketosis. Lysosomal storage disorders (e.g,, mucopolysaccharidosis, Tay-Sachs, Niemann-Pick disease, Gaucher's disease) are caused by accumulation of glycoproteins, glycolipids, or glycosaminoglycans within lysosomes in various tissues. They usually present later innfancy, not with a specific laboratory abnormality, but with organomegaly, facial coarseness and neurodegeneration and show a progressively degenerative course. Peroxisomal disorders (e.g., Zellweger syndrome and neonatal adrenoleukodystrophy) result from failure of the peroxisomal enzymes. They may present with features similar to the lysosomal storage disorders. Common features of Zellweger syndrome include large fontanel, organomegaly, Down-like facies, seizures and chondrodysplasia punctata. Others include disordered steroidogenesis (congenital adrenal hyperplasia or Smith- Lemli-Opitz), disorders of metal metabolism (Menkes syndrome, neonatal hemochromatosis). Transient hyperammonemia of the newborn is more prevalent in slightly premature infants receiving mechanical ventilation; onset is usually within the first 24 hours of life. The ammonia level may be markedly elevated and dialysis may be necessary. The cause is unknown and, if the newborn survives, there is no further evidence of impaired ammonia metabolism. 2. What are the subtle signs and some of the constellations of symptoms that may pint toward a specific metabolic disease? ‘There are a few classic presentations that should trigger consideration of an inborn error of metabolism as a reasonable possibility. These include metabolic acidosis, hyperammonemia, hypoglycemia and unusual odors. The respective clinical manifestations of these abnormalities are described below. In urea cycle defects, the common toxin is ammonia (NH3), since the urea cycle is designed to excrete excess nitrogen. Therefore, the presentation of this group of defects is quite similar. Hyperammonemia causes an encephalopathic picture. Presenting signs and symptoms include vomiting, lothargy, poor activity, poor feeding, decreased mental status, and even coma. They may eventually develop spasticity, mental retardation, seizures, and ataxia. These disorders usually present in the first few days to weeks of life as the ammonia waste product accumulates quickly, leading to serum ammonia levels which are described as "sky-high" (>1000 umol/1). The afflicted newborn very rapidly decompensates . The initial clinical presenting signs and symptoms (other than hyperammonemia) more commonly signal a serious infection of the newborn. It is very difficult to differentiate the two disease processes. However, the existence of these symptoms along with low risk for a neonatal infection may raise the index of suspicion that would lead the clinician to conduct a thorough laboratory evaluation for a metabolic condition along with the sepsis workup.broken down further and leads to liver, kidney, brain, and eye damage. Itis also life threatening if not treated. Galactosemia is one of the commonly occurring disorders of carbohydrate metabolism. This disease occurs from a deficiency of galactose-1-phosphate uridyltransferase with the deficiency most noticeable in those organs which utilize the most energy (liver, brain, kidney and adrenal gland). Over time, there is an accumulation of galactose-1-phosphate, which manifests as vomiting, lethargy, diarthea, cataracts, developmental delay and mental retardation, liver and kidney disease. In galactosemia, there is an increased likelihood of sepsis from gram negative organisms that may cause death in the neonatal period. Phenylketonuria (PKU) - PKU is a condition where the body cannot process an amino acid called phenylalanine. This can lead to brain damage. The enzyme deficiency leads to bulld-up of phenylalanine that is toxic in high levels to brain growth and nerve myelination. This causes mental retardation, abnormal behaviors and skin rashes. In addition, the PAH enzymes necessary to convert phenylalanine to tyrosine which is required for melanin synthesis. With a defective enzyme, the individual is unable to produce proper levels of tyrosine which results in poor pigmentation of skin and hair. Phenylketonuria symptoms can be mild or severe and may include mental retardation, behavioral or social problems, seizures, tremors or jerking movements in the arms and legs, hyperactivity, stunted growth, skin rashes (eczema), small head size (microcephaly), musty odor in the child's breath, skin or urine, caused by too much phenylalanine in the body, fair skin and blue eyes, because phenylalanine cannot transform into melanin — the pigment responsible for hair and skin tone (Mayo Clinic staff, 2009). Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD Def) - G6PD Deficiency is a condition where a person does not have enough of the enzyme G6PD. G6PD helps keep red blood cells healthy. GEPD deficiency is the most common known enzyme deficiency in humans. An estimated 400 million people around the world are affected. In the Philippines, around 1 in 50 children are GéPD deficient. G6PD deficiency is more common in boys than in girls. There is no known cure for G6PD deficiency. It is a lifelong condition that cannot be outgrown, However, a child with G6PD deficiency can live an active, healthy and normal life as long as he is able to avoid the substances that can trigger G6PD deficiency symptoms. Ifa child is G6PD deficient, there will be no symptoms unless he is exposed to one of the harmful substances that can trigger the breakdown of red blood cells. The child's symptoms will depend ‘on what the harmful substance was and how much of it he was exposed to. In milder cases, your child ‘may not even show any symptoms. In more serious cases, hemolysis (or hemolytic anemia) the accelerated destruction of red blood cells may happen. One of the best understood diseases from this class of metabolic diseases is Maple Syrup Urine Disease (MSUD). MSUD occurs in the immediate neonatal period, Presenting with acute decompensation within the first 2 weeks of life. Symptoms include lethargy, poor feeding, vomiting, and seizures, which eventually lead to coma and cerebral edema. Laboratory evaluation yields hypoglycemia, hyperammonemia (toa lesser degree than in urea cycle defects], acidosis, and ketosis. The urine from ‘these patients has a striking odor of maple syrup. ae CH (Congenital Hypothyroidism) Severe Mental Retardation Normal CAH (Congenital Adrenal Hyperplasia) Death e Alive and normal GAL (Galactosemia) Death or Cataracts Alive and normal PKU (Phenylketonuria) Severe Mental Retardation Normal G6PD Deficiency Severe Anemia, Kernicterus Normal. Define FEVER. How is it produced? Enumerate the causes of fever. Fever is defined as an abnormal increase in body temperature and is usually associated with disease or infection (Black,). Normal body temperature ranges from 36°C-37.5°C (Guyton, 2006) any increase in that range could be considered as a fever or even worse like malaria or dengue. Fever is produced initially through a stimuli induced by antigens and is acted upon by Pyrogens, proteins released by phagocytic cells such as monocytes and macrophages. The antigen is recognized first by lymphocytes which in turn releases lymphokines that is responsible in the synthesis of pyrogen. The protein then stimulates the hypothalamus, the thermoregulatory center, that causes the body to release heat resulting to increased body temperature (Black,). Possible causes of fever include either an infection whether bacterial or viral, abnormalities in the brain such as tumors or even the environmental influence like increase in temperature during the summer season especially in tropical areas wherein heatstroke is most common (Guyton,2006). . Define CHILLS. How does it come about? What is its significance? Chills are termed as a feeling of coldness and are synonymous with shivers due to an exposure to a cold cnvironment (Medline, 2013). Chills occur when the set point of the hypothalamus or the thermoregulatory center of the brain is drastically increased above normal level due to an infection, pyrogenic effect, tissue damage and any similar causes, the body does not immediately respond. Although the body is required to reach the new set point of the hypothalamus thus the blood temperature adjusts increasing body temperature. As the body temperature tries to reach the new set point, the individual experiences chills and feels cold. The skin also in tum feels cold since the blood vessels tend to constrict as they adjust to the increasing temperature causing the individual to shiver. When the new temperature set point has been reached the chills begin to diminish and the person will feel neither hot nor cold even though the body temperature is above the older set point or the normal temperature (Guyton, 2006). Chills are significant since they indicate that the body is shifting to a higher temperature and could imply an underlying infection or disease (Guyton, 2006 & Medline 2013). What is the difference between chills due to fever and chills due to a cold external environment? Chills can be caused by several factors but is usually associated with fever or just an influence by cold extemal environment. The difference between the two is that fever affects the immune system of the body producing defense mechanisms that lower metabolic activity and thus suppresses the capability of the body to perform normally which stimulates the hypothalamus to create a new set point increasing body temperature, contractions in the blood vessels or the muscles to produce heat. Environmental temperatures can also influence body responses such as chills almost in the same manner but no antigen or any immune related defense mechanism is involved. The body requires heat because of an external influence instead of a foreign material disrupting the normal function of the body tissues (Guyton, 2006 & Medline 2013).low serum levels of zinc developed skin ulceration. Serum levels of zinc correlated closely with the presence of edema, stunting of growth, and severe wasting. The classic "mosaic skin" and "flaky paint" dermatosis of kwashiorkor bears considerable resemblance to the skin changes of acrodermatitis enteropathica, the dermatosis of zinc deficiency. Marasmus and kwashiorkor can both be associated with impaired glucose clearance that relates to dysfunction of pancreatic beta-cells. in utero, plastic mechanisms appear to operate, adjusting metabolic physiology and adapting postnatal undernutrition and malnutrition to define whether marasmus and kwashiorkor will develop. 3. Discuss the two types of malnutrition and differentiate one from the other. What laboratory parameters are used to detect each? Marasmus involves inadequate intake of protein and calories and is characterized by emaciation. The term kwashiorkor is taken from the Ga language of Ghana and means "the sickness of ‘the weaning." Kwashiorkor refers to an inadequate protein intake with reasonable caloric (energy) intake. In marasmus, a child usually between the ages of 1 to 3 years has inadequate caloric intake leading to loss of subcutaneous fat, loose wrinkled skin, and either flat or distended abdomen resulting from atropic abdominal wall muscles. Often, children are susceptible as they go from breast milk to solid food, The affected child usually has the appearance of an “old person's face.” In kwashiorkor, the main issue is lack of protein, leading to edema, sparse hair, enlarged liver, and a distended abdomen. The ‘edema of the face and legs is different from that of marasmus. Notice four of the children with gray-blond hair, a symptom of the protein-deficiency disease kwashiorkor. Studies suggest that marasmus represents an adaptive response to starvation, whereas kwashiorkor represents a maladaptive response to starvation. Children may present with a mixed picture of marasmus and kwashiorkor, and children may present with milder forms of malnutrition, Patients with protein-energy malnutrition may also have deficiencies of vitamins, essential fatty acids, and trace elements, all of which may contribute to their dermatosis. Laboratory tests that are recommended are blood glucose, direct detection, urine examination and culture, and serum albumin. Im marasmus, blood glucose is lower than 3mol/L, haemoglobin is