Gastrointestinal Physiology - Nutrition and Metabolism PDF

GASTROINTESTINAL PHYSIOLOGY - Nutrition and metabolism Dr. Öğr. Üyesi Zülal Kaptan Learning Outcomes ❑Identify the signals from the stomach, brain, and peripheral tissues that regulate hunger and satiety ❑Explain the short-term and long-term regulatory mechanisms of food intake...

GASTROINTESTINAL PHYSIOLOGY - Nutrition and metabolism Dr. Öğr. Üyesi Zülal Kaptan Learning Outcomes ❑Identify the signals from the stomach, brain, and peripheral tissues that regulate hunger and satiety ❑Explain the short-term and long-term regulatory mechanisms of food intake ❑Discuss the brain regions involved in feeding behavior ❑Correlate the electrophysiology of smooth muscle with GI movements ❑Understand the terms and basic principles of metabolism ❑Distinguish between catabolism and anabolism ❑Understand how nutrients are used in absorptive and postabsorptive periods ❑Understand the relationship between the endocrine system and metabolism ❑Define the basal metabolic rate ❑Know the factors affecting metabolic rate Nutritional requirements The body’s energy requirements must be met by the caloric value of food to prevent catabolism of the body’s own fat, carbohydrates, and protein. Vitamins and minerals do not directly provide energy but instead are required for diverse enzymatic reactions. Living tissue is maintained by the constant expenditure of energy. ▪ This energy is obtained directly from ATP and indirectly from the cellular respiration of glucose, fatty acids, ketone bodies, amino acids, and other organic molecules. ▪ These molecules are ultimately obtained from food, but they can also be obtained from the glycogen, fat, and protein stored in the body. Food intake What starts a meal? 1. Environmental signals: Meal time, tables, food smells 2. Signals from the stomach (Ghrelin) ▪ Blood levels of ghrelin increase with hunger and decrease after eating. Injections of food into the blood do not suppress ghrelin secretion, while food entering the duodenum suppresses ghrelin secretion. 3. Metabolic signals (Glycoprivation (deprivation of cells of glucose) ve lipoprivation (deprivation of cells of lipids)) What stops a meal? Short-term satiety signals: It begins long before food is digested (with the ingestion of the meal). As food travels, the stomach, small intestine, and liver can each send a signal to the brain that food has been ingested and is on its way to absorption. Long-term satiety signals: It occurs in fat tissue, which contains long- term nutrient storage. Brain mechanisms Target of hunger and satiety signals → Brain Brain stem: Digestive behaviors are phylogenetically old, so chewing and basic swallowing behaviors are programmed by phylogenetically old brain circuits. Various regions of the hypothalamus Cerebral cortex and amygdala: Appetite (cognitive regulation of feeding) Hypothalamus Two regions of the hypothalamus stand out: lateral area ve ventromedial area (Hunger and satiety centers) The interaction between these two structures is important Lateral: chronic active Ventromedial: Transient, inhibits lateral In the hypothalamus: Lateral hypothalamus: hunger center Ventromedial nucleus: satiety center If the lateral hypothalamus is destroyed → organic anorexia develops. If the ventromedial nucleus is destroyed → obesity develops. If the lateral hypothalamus is stimulated→ obesity If the ventromedial nucleus is stimulated → anorexia What regulates the activity of these two centers: impulses from the periphery Sensory mechanical information from the gastrointestinal tract (explains the feeling of early satiety) Signals from gastrointestinal hormones (CCK, glucagon etc) Chemical signals in the blood related to nutrients that make you feel full (such as glucose and fatty acids) (late feeling of satiety) Cerebral cortex and amygdala-derived signals affecting feeding behavior (If I eat more, I will gain weight.) A drop in body temperature below a certain level stimulates appetite, while a rise in body temperature suppresses appetite. Metabolic signals- Glucostatic hypothesis: Increased glucose utilization in the hypothalamus causes a feeling of satiety. Glucostats (glucose-sensitive cells) in the ventromedial nucleus are activated (normally silent) when blood glucose concentration increases and suppress the lateral hypothalamus. The suppression is released when blood glucose concentration decreases again. Metabolic signals-Lipostatic hypothesis: Leptin released from adipose tissue No role for ventromedial nucleus in the leptin hypothesis, related to the interaction of the other 3 nuclei lateral hypothalamus, arcuate, paraventricular If leptin increases, the arcuate nucleus is directly affected. When the arcuate nucleus is stimulated by leptin; 1. It activates sympathetic centers in the brainstem. As a result, metabolic activity increases. Appetite is suppressed. 2. Stimulates the paraventricular nucleus. (Where TRH, CRH is synthesized.) Helps with the feeling of satiety related to metabolism. 3. 2 neuropeptide release increases. 1. Alpha-melanocyte stimulating hormone (α-MSH) 2. Cocaine amphetamine related transcript (CART) These are two appetite suppressant neuropeptides. What they do is they suppress the lateral hypothalamus. Digestive activity is over, the amount of leptin decreases, what happens then? 1. Arcuate nucleus cannot stimulate the sympathetic system 2. Arcuate nucleus cannot stimulate the paraventricular nucleus 3. Arcuate nucleus secretes 2 different appetite-stimulating peptides. 1. Neuropeptide Y 2. Agouti-related peptide (AgRP) These two stimulate the lateral hypothalamus and the feeling of hunger occurs. Besides, two peptides are synthesized in the lateral hypothalamus: MCH (melanocyte concentrating hormone) Orexin A-B (hypocretin) These two peptidergic pathways have monosynaptic connections with limbic structures and the prefrontal cortex: Responsible for cognitive, emotional and motivational components of eating behavior (refrigerator inspection) Endocannabinoids facilitate release of MCH and orexin Summary: Orexigenic molecules: Neuropeptide Y (NPY), agouti- related peptide (AGRP), melanocyte concentrating hormone (MCH) ve orexin (hypocretin) + endocannabinoids Anorexigenic molecules: Alpha-melanocyte stimulating hormone (α-MSH), cocaine amphetamine related transcript (CART) Metabolism Metabolism refers to all chemical reactions that occur in the body. There are two types of metabolism: catabolism and anabolism. Chemical reactions that break down complex organic molecules into simpler ones → Catabolism In general, catabolic (decomposition) reactions are exergonic: They release chemical energy stored in organic molecules. Chemical reactions that combine simple molecules and monomers to form complex structural and functional components of the body → Anabolism Anabolic reactions are endergonic. Metabolism is an energy balancing effect between catabolic (decomposition) reactions and anabolic (synthesis) reactions. The molecule that participates most in energy exchanges in living cells → ATP (adenosine triphosphate) Of the energy released in catabolism; ▪ approximately 40% is used for cellular functions, ▪ the rest is converted into heat. → 40% efficiency Metabolic adaptations What does the regulation of metabolic reactions depend on? The chemical environment within body cells, such as ATP and oxygen levels Signals from the nervous system and endocrine system How long has it been since the last meal? (absorptive vs post- absorptive state) ▪ During the absorptive state, nutrients enter the bloodstream and glucose is readily available for ATP production. ▪ In the post-absorptive state, absorption of nutrients from the GI tract is complete and energy needs must be met with fuels already in the body. A typical meal requires about 4 hours for complete absorption; with three meals per day, the absorptive state exists for about 12 hours each day. Assuming no snacks between meals, the other 12 hours—typically late morning, afternoon, and most of the night—are spent in the post-absorptive state… Metabolism in absorptive state energy needs Meeting 1. Glucose catabolism 2. Catabolism of some amino acids 3. Catabolism of several dietary lipids 4. Protein synthesis 5. Glycogenesis Storage 6. Lipogenesis 7. Transport of triglycerides from the liver to adipose tissue Meeting energy needs 1. Glucose catabolism Most cells in the body produce most of their ATP by catabolizing glucose. Glucose is therefore the body's main source of energy in the absorptive state. About 50% of the glucose absorbed from a typical meal is catabolized by cells in the body to produce ATP. 2. Catabolism of some amino acids Some amino acids enter hepatocytes where they are deaminated to keto acids. Keto acids can enter the Krebs cycle for ATP production or can be used to synthesize glucose or fatty acids. 3. Catabolism of several diet lipids During the absorptive state, only a small portion of dietary lipids are catabolized for energy. Storage 4. Protein synthesis Many amino acids enter body cells such as muscle cells and hepatocytes for the synthesis of proteins. 5. Glycogenesis The portion of glucose that may exceed the body's needs that is taken up by the liver and skeletal muscle and then converted to glycogen (glycogenesis). (10%) 6. Lipogenesis The liver can also convert excess glucose or amino acids into fatty acids for use in the synthesis of triglycerides (lipogenesis). In general, about 40% of the glucose absorbed from a meal is converted into triglycerides. 7. Transport of triglycerides from the liver to adipose tissue Some fatty acids and triglycerides synthesized in the liver remain there, but hepatocytes package most of them into very low-density lipoproteins (VLDL), which carry lipids to adipose tissue for storage. Regulation of metabolism in the absorptive state Shortly after meal, glucose dependent insulinotropic peptide (GIP), blood glucose and rising levels of certain amino acids, stimulates pancreatic beta cells to release the hormone insulin. Insulin, It promotes the entry of glucose and amino acids into the cells of many tissues. It stimulates the conversion of glucose to glycogen (glycogenesis) in both liver and muscle cells. It increases the synthesis of triglycerides (lipogenesis) in the liver and adipose tissue. It stimulates protein synthesis. In general, insulin increases the activity of enzymes required for anabolism and the synthesis of storage molecules; at the same time, it decreases the activity of enzymes required for catabolic or breakdown reactions. Metabolism in the post-absorptive state Approximately 4 hours after the last meal, absorption of nutrients from the small intestine is complete and blood glucose levels begin to fall. The main metabolic challenge during the post-absorptive state is: to maintain normal blood glucose levels of 70-110 mg / 100 mL Homeostasis of blood glucose concentration is of particular importance for the nervous system, retina, and erythrocytes: The predominant fuel molecule for ATP production in the nervous system is glucose because fatty acids cannot cross the blood-brain barrier. Erythrocytes obtain all of their ATP from the glycolysis of glucose because they do not have mitochondria. 1. Liver glycogenolysis 2. Skeletal muscle glycogenolysis 3. Lipolysis Glucose generation 4. Protein catabolism 5. Gluconeogenesis 6. Catabolism of fatty acids 7. Catabolism of lactic acid 8. Catabolism of amino acids Glucose preservation 9. Catabolism of ketone bodies Glucose generation 1. Glycogenolysis in the liver In the post-absorptive state, a major source of blood glucose is liver glycogenolysis, which can provide approximately 4 hours of glucose supply. 2. Glycogenolysis in skeletal muscle Glycogenolysis can also occur in skeletal muscle. However, in skeletal muscle, glucose generated from glycogenolysis is catabolized to provide ATP for muscle contraction. 3. Lypolysis In fat tissue, triglycerides are broken down into fatty acids and glycerol, which are released into the blood. Glycerol is taken up by the liver and converted into glucose, which is then released into the bloodstream. 4. Protein catabolism The moderate breakdown of proteins in skeletal muscle and other tissues releases amino acids, which can then be converted into glucose by the liver. 5. Gluconeogenesis In the post-absorptive state, new glucose is formed from non-carbohydrate sources. Examples of gluconeogenesis include the formation of glucose from lactic acid, glycerol, or amino acids. Glucose preservation Preserving glucose means that most body cells switch to other fuels besides glucose as their main energy source, leaving more glucose in the blood for the brain and erythrocytes. 6. Catabolism of fatty acids Fatty acids released by lipolysis of triglycerides cannot be used for glucose production, but most cells can catabolize fatty acids directly. 7. Catabolism of lactic acid Cardiac muscle can produce ATP anaerobically from lactic acid. 8. Catabolism of amino acids In hepatocytes, amino acids can be directly catabolized to produce ATP. 9. Catabolism of ketone bodies Hepatocytes also convert fatty acids into ketone bodies that can be used by other tissues, such as the heart and kidneys, for ATP production. Regulation of metabolism in the post-absorptive state Both hormones and the sympathetic division of the autonomic nervous system regulate metabolism during the postabsorptive state.  When blood glucose concentration begins to fall→ Glucagon from pancreatic alpha cells ↓ Main target tissue: liver Main effect: gluconeogenesis, glycogenolysis Thus, it increases blood glucose concentration. Low blood glucose→ Glucose-sensitive neurons in the hypothalamus→ Activates the sympathetic branch of the ANS From sympathetic nerve endings → norepinephrine From adrenal medulla → epinephrine ve norepinephrine Effects: glycogenolysis, lipolysis Thus, glucose and free fatty acid levels in the blood increase. Stressful situations such as low blood glucose, heat or cold, fear or trauma → cortisol release from the adrenal gland Effects: gluconeogenesis, lypolysis, protein catabolism Summary Use of Nutrients in Metabolism in Absorptive and Post-Absorptive States Nutrient Absorptive State Post-Absorptive State Carbohydrates Used immediately for energy (Primarily Stored as glycogen in the liver and muscle Glycogen is broken down into glucose in the glucose; also (glycogenesis) liver and kidney (glycogenolysis) fructose and Excess converted to fat and stored in galactose) adipose tissue (lipogenesis) Protein Most amino acids go to the tissues for Amino acids separated from proteins are (Amino acids and aerobic metabolism used for ATP production or glucose some small Excess is converted into fat and stored in peptides) production (gluconeogenesis) adipose tissue (lipogenesis) Triglycerides are broken down into fatty Fat Stored as triglycerides, mainly in the liver acids and glycerol (lipolysis) (Fatty acids, and fat tissue (lipogenesis) Glycerol is used to produce glucose triglycerides and Used for steroid synthesis or as a membrane cholesterol) Fatty acids are used for ATP production component (cholesterol) Fatty acids are converted into ketone bodies Basal metabolic rate (BMR) Basal metabolic rate is the metabolic rate under basal conditions. It is the energy spent to maintain vital functions while resting without moving for 24 hours. The body is in a state of rest and fasting called the basal state. BMR in adults→ 1200-1800 kcal/day or approximately ▪ 24 kcal/kg body mass in adult males ▪ 22 kcal/kg body mass in adult females Factors affecting BMR Hormones: Thyroid hormones (thyroxine and triiodothyronine) are the main regulators of BMR. As blood levels of thyroid hormones rise, BMR increases. However, the response to changing thyroid hormone levels is slow (may take several days). Other hormones have minor effects on BMR. Testosterone, insulin ve growth hormone can increase metabolic rate by 5-15%. Age: A child's metabolic rate is approximately twice that of an older person due to the higher reaction rates associated with growth. Sex: Lower in women outside of pregnancy and lactation Total metabolic rate (TMR) Total energy expenditure by the body per unit of time Three components contribute: ▪ BMR (60% of TMR) ▪ Physical activity (adds 30-35%, lower in sedentary individuals) ▪ Food intake-induced thermogenesis (5-10% of TMR) Exercise: During strenuous exercise, metabolic rate can increase up to 15 times the basal rate. In well-trained athletes, this rate can increase up to 20 times. Food intake: Digestion, absorption and storage of nutrients increases metabolic rate. → food-induced thermogenesis Body temperature: As body temperature rises, metabolic rate increases. Every 1°C increase in core temperature increases the rate of biochemical reactions by about 10%. As a result, metabolic rate can increase significantly during fever. Nervous system: During exercise or stressful situation → sympathetic division of the autonomic nervous system: Postganglionic neurons → secrete norepinephrine Adrenal medulla → epinephrine ve norepinephrine Both epinephrine and norepinephrine increase the metabolic rate of body cells. BMR Measurement It can be determined using whole body calorimetry to measure the amount of heat given off by the body (direct calorimetry) It can be determined by measuring the volume of oxygen consumed by the body over a short period of time (indirect calorimetry). Since many factors affect metabolic rate, metabolic rate is measured under standard conditions. 1. The patient should not eat for at least 12 hours before the test. 2. The patient should be mentally and physically relaxed. 3. The patient's core body temperature should be normal. 4. The room temperature should be optimal (20 - 25 °C). DIGESTIVE SYSTEM DISORDERS