Understanding Physiology and Pathophysiology of Metabolism

Metabolism is a reference to the summation of all energy transformation associated with each chemical reaction in the body. Food is the sole source of energy for the body nd stores energy in chemical form, measurable by the caloric content. Energy cannot be created nor destroyed, but can be transformed from one form to another. Mostly, calorie burn means that calorie energy is being converted from the chemical form stored within the body to heat or mechanical form not stored in the body.

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There are two types of chemical reactions:

a) Catabolism: this breaks down nutrient molecules to release useable energy. The energy released is stored in adenosine triphosphate (ATP) molecules and is used to power all processes at the cellular level.

b) Anabolism: this uses up the ATP energy made available through catabolism to construct molecules in the body such as muscle and fat.

Therefore, anabolism and catabolism are antagonists, and the overall maximum is the sum of all reactions under the two categories. The ATP generated in catabolic reactions can be used in 2 ways:

a) It can be used to power energy absorbing anabolic reactions. The energy used in anabolism remains stored in the body within the chemical bonds of the molecule that have been synthesized, for example, muscle, fat, and bone.

b) It can be used to help power movement of muscles and support non-anabolic aspects of the body at cellular level. This energy is converted to either heat or mechanical energy that is not stored within the body and is considered to have been burned off.

Basal metabolic rate (BMR)- This is the amount of energy, measured in calories, that the body must burn to keep itself alive. The calories burned to meet BMR requirement include only those used to keep body tissues alive and support function of vital organs.

Total caloric expenditure- this is the total number of calories burned in a given day; it is determined by adding BMR and calories burned to support physical activity and digestion.

A person with high metabolism has relatively high BMR and must burn more calories to meet life sustaining energy requirement. In contrast, a person with low metabolism has low BMR, and therefore burn fewer calories while at rest than people with high BMR.

Metabolism can be increased by increasing muscle mass; muscle burns calories at rest and is, therefore, a contributing factor to BMR. Each pound of muscle in the body adds five calories per day to the BMR. Resistance training to increase muscle mass is a highly recommended component of any fitness plan.

Energy balance and clinical presentations in endocrinology; principles for clinical management.Energy in refers to the amount of energy stored within the body tissues while energy out refers to the energy used for maintenance at rest, physical activity and movement and food digestion, absorption and transport. The bodys energy needs can be measured by the amount of oxygen consumed.

Negative energy balance occurs when there is more energy out than energy in. Severe negative balance can lead to a decline in metabolism, the decrease in body mass, reduction in thyroid hormone, reduction in testosterone levels, an inability to concentrate and reduction in physical performance. It also leads to weight loss as the body detects an energy deficit and fat reserves are called upon to make a difference.

Positive energy balance occurs when there is more energy in than out. Overfeeding has its ramifications regarding weight gain, health, and cellular fitness. It causes plaques to build up in the arteries, increased circulating cholesterol, resistance to insulin and predisposes one to risks of cancer.

A calorie restriction without metabolic intervention leads produces equal losses in lean mass and fat mass. Monitoring the lifestyle helps to control properly energy balance, thus preventing excessive swings in either direction.

Energy balance is controlled by a rich network of systems; the hypothalamus, neural connections in the body and hormone receptors work in unison to carry out this task. Information is relayed about energy repletion/depletion, diurnal clock, physical activity level, reproductive cycle, developmental state, and stressors. The hypothalamus regulates gastro intestinal related signals, signals arising from macronutrient metabolism and chemical signals from both central and peripheral nervous system that are anabolic( hunger-stimulating) or catabolic (hunger suppressing) to determine biological drive whether to eat. Biological signals are also affected by culture, behavior, and environmental factors.

The energy balance equation is used in weight loss counseling to predict the magnitude of body fat loss in response to reduced energy intake. For example, an overweight individual might be advised to create a 500kcal deficit by reducing consumption of specific food in their diet.

Inborn errors of metabolism

These are the gene mutations or deletions that alter metabolism in the body. IEM result in the disruption of a wide range of metabolic pathways including metabolism of proteins, carbohydrates, lipids, nucleic acids, steroids, and metals. IEM can result from deficiency or overactivity of an enzyme, deficiency of a vital cofactor in enzymatic activity, a malfunction in degradation or transport process, leading to accumulation of upstream metabolites or deficiency of downstream metabolites, hence toxicity. Accumulation of toxic metabolites as seen in hereditary hemochromatosis ( causing liver cirrhosis) increased rate of mutation as seen in mitochondrial disorders are ways in which IEM could predispose one to cancer. Some common types of IEM include:

a) Amino acid disorders, such as Marple Syrup urine disorder, which are characterized by the inability to metabolize a particular essential amino acid. The amino acids, therefore, accumulate to toxic levels. MSUD, for example, is characterized by a distinctive sweet odor of urine, poor feeding, vomiting, and lethargy. If not treated, it causes seizures, coma, and death.

b) Urea cycle disorders caused by defect or absence of enzymes involved in the urea cycle, leading to of ammonia in accumulation blood. Citrullinemia, for example, is an autosomal recessive disorder that causes excessive accumulation of ammonia in body fluids. This leads to toxicity that manifests as lethargy, appetite loss, lethargy, irritability and seizures

c) Lysosomal storage disease: which is caused by defects in lysosomal enzymes, thus increased storage of large undigested molecules in lysosomes. An example is Pompe disease, caused by an accumulation of glycogen in lysosomes. Glycogen builds up causes muscle weakness and damages nerve cells.

Gut hormones concerning obesity and appetite.

Gut hormones include a group of hormones secreted by enteroendocrine cells in the stomach, pancreas, and small intestines.They include cholecystokinin, secretin, insulin, vasoactive intestinal polypeptide, among others.

Ghrelin is a hormone released from the stomach and liver and is often known as the hunger hormone as it is found in high levels in fasting individuals. Ghrelin has receptors in the hypothalamus which contribute to its effects on appetite.It promotes feeding and adiposity. In the rodent, ghrelin increases respiratory quotient, suggesting reduced fatty acid oxidation and increased glycolysis, which would favor fat deposition.

Leptin regulates hypothalamic networks to inhibit food intake and body weight gain. The absence of leptin results in extreme obesity in man. Obese individuals have a reduced circulating ghrelin compared to lean individuals. This is because appetite-inhibiting leptin is increased in obese individuals, raising the probability that ghrelin and leptin are constituents of a dynamic feedback system in weight regulation.

Pancreatic polypeptide(PP) is secreted by PP cells of the islets of Langerhans in the pancreas. PP is found to reduce food intake in rodents and normal weight human subjects. It has a high affinity for Y4 receptors which is found widely in the brainstem and hypothalamus, areas key in central control of appetite. Also, PP also reduces gastric emptying, providing feedback to central satiety centers via the vagus nerve. Administration of PP causes weight loss, making it a good option for obesity therapy.

Oxyntomodulin is secreted by entero-endocrine L cells. It inhibits both gastric acid secretion and pancreatic enzyme secretion, as well as delaying gastric emptying. It therefore significantly decreases food intake and helps in reducing body weight gain. OXM presents an exciting prospect for prolonged treatment of obesity.

Peptide YY is produced by enteroendocrine L cells of the distal gut in response to an oral nutrient load. Its levels start to rise around 15 minutes after caloric ingestion before nutrients reach distal gut.it acts via Y2 receptors which are found throughout CNS, especially hypothalamus, an area of key control of enzymes. It cause a reduction in gastric emptying and has an inhibitory effect on food intake, thus promoting weight loss.

Pancreatic hormones and diabetes mellitus

Pancreatic cells produce hormones which are involved in body sugar regulation. Insulin is produced by the beta cells of the pancreas, and it regulates carbohydrate and fat metabolism by promoting absorption of glucose from the blood into skeletal muscles and fat tissue.

Diabetes mellitus is a lifelong chronic condition that affects the bodys ability to use the energy found in food. Glucose, a product of digestion, fuels the cells in the body and is taken into the body cells by glucose transporter. Insulin is needed for glucose to be absorbed. Diabetes mellitus is caused by decreased sensitivity of cells to insulin or inability to produce insulin.

a) Diabetes mellitus 1: also known as juvenile diabetes, it is an autoimmune condition caused by the body attacking its pancreas with antibodies. The damaged pancreas, therefore, does not make insulin. It could be genetic or due to faulty beta cells, Symptoms include weight and muscle bulk loss, feeling tired and thirsty constantly and passing more urine.

b) Diabetes mellitus 2: also known as no insulin dependent, is caused by the resistance of body cells to insulin. Its symptoms include excessive thirst, passing more urine, lethargy, itchy skin infections, blurred vision, abnormal weight gain, headaches, dizziness and muscle cramps. Unlike diabetes mellitus 1, type 2 has no cure. It can, however, be managed through lifestyle modifications such as maintaining a constant weight.

CHEMICAL PATHOLOGY AND RELATED DISCIPLINES OF MEDICINE

This is the branch of medicine involved with biochemical basis of disease and the use of biochemical tests for screening, prognosis, and management. Chemical Pathologists have two significant clinical roles. First, they have to liaise with healthcare professionals such as nurses to give advice on the appropriate tests to be used and how to make a good interpretation of the results from the tests when investigating patients. Second, they must have direct responsibility for patients in out patient clinics or wards. Thus, they can treat a wide range of metabolic disorders such as high cholesterol, diabetes, hormone imbalance and kidney stones.

Chemical pathology includes all nonmorphological pathology tests.These tests are usually carried out on blood and urine but may also be applied to other body fluids such as gastric aspirates and cerebrospinal fluids.

Biochemical tests could be requested depending on two principal approaches:

a) The discretionary or selective test was requesting in which tests are requested based on clinical information such as signs, symptoms, and previous laboratory tests

b) S...