Outline for Midterm 1. Chapter 22: Updated for Yese and Nessa

MFSON PHYS 202 Dr. Shayo M.D. 10/07/2022 Outline for Midterm 1 Make sure you review all the sections of each of the chapters (1-7, 22) in the physiology book! Chapter 1: 1.1 Physiology is an Integrative Science – Review some of the definitions describing the study of physiology and be able to distinguish it from other scientific disciplines. 1.2 Function and Mechanism 1.3 Themes in Physiology – Review the main themes in physiology. 1.4 Homeostasis – Review the process of Homeostasis, and be able to 1.5 Control Systems and Homeostasis – Be able to distinguish between the two control systems (endocrine and neuro) we discussed in lecture and how each system causes its effects in tissues. 1.6 The Science of Physiology Chapter 2 2.1 Molecules and Bonds 2.2 Noncovalent Interactions 2.3 Protein Interactions- Understand and be able to describe all levels of protein structure: Primary Secondary, Tertiary, and Quaternary. Chapter 3 3.1 Functional Compartments of the Body – Review all the cavities in the body, and be able to understand the breakdown of the fluid compartments in the body. 3.2 Biological Membranes- Review the cell membrane, all the components that make up the phospholipid bilayer. 3.3 Intracellular Compartments – Review the major organelles in the cell and their function. 3.4 Tissues of the Body - Know the function of all 4 major types of the tissues in the body. Be able to distinguish key features in each type of tissues. Review tissue histology and the purposes for the different 3.5 Tissue Remodeling- Review how adipose tissue is utilized as an energy source in the body 3.6 Organs- Know what organs are responsible for processing which macromolecules in the body. Chapter 4: 4.1 Energy in Biological Systems 4.2 Chemical Reactions- Review the main types of chemical reactions and how they pertain to physiology. 4.3 Enzymes- Review enzyme functions and be able to distinguish some of enzymes by their prefix 4.4 Metabolism- Review anabolism and catabolism, and be able to out line the main process that allow cells to generate ATP in the cell, and the products of these processes. Chapter 5 5.1 Osmosis and Tonicity- Review some of the different intracellular/extracellular ions, proteins, and molecules and their ability to exert osmotic pressure in vivo. 5.2 Transport Processes- Review the different mechanisms that allow transporter proteins to move molecules into and out of the cell. 5.3 Diffusion- Review the process of diffusion and how different chemical and physical properties of molecule affect the rate. 5.4 Protein-Mediated Transport- Be able to distinguish the differences between the different types of facilitated transport. Understand the difference between types of active transport. 5.5 Vesicular Transport- Understand how vesicular transport is facilitated by the cell, and what energy requirements must be met. 5.6 Epithelial Transport- Review how epithelial cells are able to transport molecule from the apical membrane to the basal membrane. 5.7 The Resting Membrane Potential 5.8 Integrated Membrane Processes: Insulin Secretion Chapter 6: 6.1 Cell-to-Cell Communication – Review the different ways that cells can communicate with each other. Understand how neurotransmitters/hormones can exert their effect withing the cell. 6.2 Signal Pathways – Review the different types of receptors and how signal molecules can cause a cascading effect in the cell. 6.3 Novel Signal Molecules - Review and be able to distinguish chemically gated ion channels, voltage gated ion channels, and G-Protein coupled signaling pathways. 6.4 Modulation of Signal Pathways – Review the concepts of receptor specificity, competition saturation, and how agonist and antagonists exert their effects on receptors. 6.5 Homeostatic Reflex Pathways – Review all endocrine, neuroendocrine, and neural reflex pathways. Chapter 7: Review the endocrine system and make sure you understand all the feedback mechanisms. 7.1 Hormones- Review where all endocrine glands and know where all hormones are released in the body. 7.2 The Classification of Hormones – Review and be able to distinguish the different classes of hormone release by the endocrine system. 7.3 Control of Hormone Release- Review how endocrine gland limits excess production of hormones, and 7.4 Hormone Interactions- Review the functions of all the hormones, the tissues affected, and their overall functions. Be able to distinguish key hormones that will be expressed in fed and un-fed states. Be able to distinguish synergistic, permissive, and antagonistic effects of hormones. 7.5 Endocrine Pathologies – Review and study the key hyper, and hypo secretions disorders of the endocrine system. 7.6 Hormone Evolution- Know how different hormones are synthesized in the body and some of the precursor that will allow Chapter 22: 22.1 Appetite and Satiety – Review the adipokines and understand how they are related to hunger and satiety. Some of the chemical signals that influence food intake and satiety include neuropeptides, “brain-gut” hormones secreted by the GI tract, and chemical signals secreted by adipose tissue called adipocytokines or adipokines for short. The feeding and satiety centers are located in the hypothalamus. 2 Classic Theories for Regulation of Food Intake 1. Glucostatic Theory - glucose metabolism by hypothalamic clusters regulates food intake 2. Lipostatic Theory - a signal from the body’s fat stores to the brain modulates eating behavior so that the body maintains a particular weight. Obesity results from disruption of this pathway. >>Leptin - protein hormone, synthesized in adipocytes, provided evidence for lipostatic theory (ADIPOSE CELLS); Adipocytes secrete the hormone Leptin. >>>>Acts as negative feedback loop between adipose tissue & brain ->fat stores increases, adipose cells secrete more LEPTIN = food intake decrease >>>>Synthesized in adipocytes under control of the obese gene. >>Neuropeptide Y (NPY) - brain neurotransmitter that is the stimulus for food intake (CO-EXPRESSED IN HYPOTHALAMUS) >>Gherlin - secreted by the stomach during fasting & increases hunger when infused into human subjects (STOMACH) 22.2 Energy Balance – Review and outline how the body is able to balance energy input with energy output to maintain homeostasis. Review all the factors that affect the BMR. First law of Thermodynamics - total amount of energy in the universe is constant. Energy Intake is Energy Output >>>>>All energy goes into ta biological system can be counted for. Energy Intake - energy in nutrients we eat, digest, absorb Energy Output - combo of work performed & energy returned to the environment as heat. WORK IN EQUATION TAKES 3 FORMS 1. Transport Work - moves molecules from one side to the other side. Bring materials into and out of the body and transfer them between compartments; Ex: bringing glucose molecules inside brain cells so one can think - maintaining a concentration gradient across a membrane is Transport Work. 2. Mechanical Work - uses intracellular fibers and filaments to create movement. External work (skeletal muscle contraction) & internal work (movement of cytoplasmic vesicles & pumping of the heart). 3. Chemical Work - growth, maintenance & storage of information & energy. Ex: ATP; chemical bonds of glycogen & fats; body building exercises makes muscles bigger >>The only way to increase Energy Output: Walking & Exercise >>To control Energy Intake: Watching what you eat Many Factors Influence Metabolic Rate Basal Metabolic Rate (BMR) - individuals’ lowest metabolic rate; when asleep (difficult to measure); factors that increase BMR are thyroid hormones and epinephrine Resting Metabolic Rate (RMR) - metabolic rate is measured after a 12-hour fast in a person who is awake but resting How to determine a person’s metabolic rate: 1. Oxygen 2. Heat released 3. CO2 produced 6 FACTORS THAT AFFECT METABOLIC RATE IN HUMANS: 1. Age and Sex 2. Amount of lean muscle mass 3. Activity level 4. Diet 5. Hormones 6. Genetics Other Factors a person can voluntarily control only 2: 1. Energy Intake (food eaten) 2. Level of Physical Activity - with strength training = increase lean muscle mass = RMR increases = Increased additional energy use which in turn decreases calories that go into storage Diet-induced Thermogenesis - increase in heat production after eating >>Glycogen & fat are the 2 primary forms of energy storage in the human body 22.3 Metabolism – Review how Glucose, Fat, and Amino Acids, are used by different tissues in the body to produce energy. Metabolism - the sum of all the body’s chemical reactions Reaction Pathways: 1. Extract energy from nutrients 2. Use energy for work 3. Store excess energy so that it can be used later Anabolic Pathways - reactions that require a net input of energy & reactions that result in the synthesis of large biomolecules from smaller ones. Ex: (1st step of Glycolysis: Glucose gains a phosphate to become a larger molecule, 6-phosphate Catabolic Pathways - those that break large molecules from smaller ones Ex: (End of Glycolysis) 6carbon glucose molecule has been converted to two 3-carbon pyruvate molecules. ->the breakdown of one glucose to two pyruvate makes glycolysis a catabolic pathway; reactions that result in the breakdown of large biomolecules Catabolism - lage molecules broken into smaller ones Metabolism Divided into 2 States: Fed State & Fasted State Fed State or Absorptive State - (anabolic state) which the energy of nutrient biomolecules is transferred to high-energy compounds or stored in the chemical bonds of other molecules; When blood glucose levels increase only insulin is secreted in fed state. >During absorptive state, the liver synthesizes glycogen. Fasted State or Postabsorptive State - once nutrients from a recent meal are no longer in the bloodstream and available for use by tissues, the body enters the fasted state. The body taps into its stored reserves. (Catabolic State) because cells breakdown large molecules into smaller molecules. The energy released by breaking down chemical bonds of large molecules is used to do work. When blood glucose levels decrease, glucagon is secreted in fasted state Biochemical Pathway - a series of interconnected chemical reactions. Biomolecules we Ingest are destined to meet on of the three fates: 1. Energy - energy is trapped in ATP, phosphocreatine and other high-energy compounds which is used to do Mechanical Work. 2. Synthesis - needed for growth and maintenance of cells and tissues 3. Storage - amount of food exceeds the body’s requirements for energy and synthesis, the excess energy goes into storage in the bonds of glycogen & fats. Storage makes energy available for times of fasting. 4. Nutrient pools - nutrients that are available for immediate use located primarily in the plasma. >Free fatty acids form the primary pool of fats in the blood. They can be used as an energy source by many tissues but are also easily stored as fat (triglycerides) in adipose tissue. >Carbohydrates are absorbed mostly as glucose. Plasma glucose concentration is the most closely regulated of the three nutrient pools because glucose is the only fuel the brain can metabolize, except in times of starvation. If the glucose pool falls below a certain level, only the brain has access to glucose. This conservation measure ensures that the brain has an adequate energy supply. Just as the circulatory system gives priority to supplying oxygen to the brain, metabolism also gives priority to the brain. Normal range of glucose pool=most tissues use glucose for their energy source. Excess glucose goes into storage as glycogen. Glycogenesis - synthesis of glycogen from glucose Lipogenesis - glycogen stores are limited, however, and additional excess glucose is converted to fat by LIPOGENESIS. Glycogenolysis - If plasma glucose concentrations decrease, the body converts glycogen to glucose through GLYCOGENOLYSIS. The body maintains plasma glucose concentrations within a narrow range by balancing oxidative metabolism, glycogenesis, glycogenolysis, and lipogenesis. If homeostasis fails and plasma glucose exceeds a critical level, as occurs in diabetes mellitus, excess glucose is excreted in the urine. Glucose excretion takes place only when the renal threshold for glucose reabsorption is exceeded. The amino acid pool of the body is used primarily for protein synthesis. However, if glucose intake is low, amino acids can be converted into glucose through the pathways known as gluconeogenesis. Gluconeogenesis - refers to synthesis (to build) of new glucose from noncarbohydrate precursors (like PROTEINS/Amino Acids -main source for glucose), provides glucose when dietary intake is insufficient or absent. (opposite of glycolysis (to break) ) During starvation, GLUCONEOGENESIS INCREASES. Both gluconeogenesis and glycogenolysis are important backup sources for glucose during periods of fasting. Glucagon stimulates gluconeogenesis and targets the liver. Both insulin and glucagon are peptide hormones that target liver cells. The responses of the target cells to these two hormones are the opposite of each other implying that each of the two hormones uses a different second messenger. 22.4 Fed-State Metabolism (REMEMBER THIS IS THE BUILDING UP STATE OF METABOLISM)– Review and understand how biomolecules are processed by different organs during the fed-state. Fed State following ingestion of nutrients is ANABOLIC: absorbed nutrients are being used for energy, synthesis & storage. Carbohydrates make ATP. Glucose is the primary substrate for ATP production. Glucose absorbed from the intestine enters the hepatic portal vein and is taken directly to the liver, 30% of all ingested glucose is metabolized. 70% continues in the bloodstream for distribution to the brain, muscles, and other organs and tissues. Brain relies solely on GLUCOSE as its energy source. No glucose brain cell will die. Glucose moves from interstitial fluid into cells by membrane GLUT transporters. Most glucose absorbed from a meal goes immediately into glycolysis and the citric acid cycle to make ATP. Some glucose is used by the liver for lipoprotein synthesis. Glucose that is not required for energy and synthesis is stored either as glycogen or fat. The body’s ability to store glycogen is limited, so most excess glucose is converted to triglycerides and stored in adipose tissue. The respiratory quotient is highest for consumed carbohydrates compared to proteins and fats. Glycogen, a large polysaccharide, is the main storage form of glucose in the body. Glycogen with high concentrations: the liver and skeletal muscles. Glycogen in skeletal muscles provides a ready energy source for muscle contraction. Glycogen in the liver acts as the main source of glucose for the body in periods between meals (the fasted state). It is estimated that the liver keeps about a 4hour supply of glucose stored as glycogen. CARBOHYDRATES ARE USED IMMEDIATELY FOR ENERGY. Triglycerides are broken down into Glycerol, which feeds into glycolysis, and Fatty Acids, which are metabolized to Acetyl CoA. Amino Acids Make Protein -Most amino acids absorbed from a meal go to the tissues for protein synthesis. -Amino acids are taken first to the liver by the hepatic portal system. The liver uses them to synthesize lipoproteins and plasma proteins, such as albumin, clotting factors, and angiotensinogen. -If glucose intake is low, amino acids can be used for energy. However, if more protein is ingested than is needed for synthesis and energy expenditures, excess amino acids are converted to fat. Some bodybuilders spend large amounts of money on amino-acid supplements advertised to build bigger muscles. But these amino acids do not automatically go into protein synthesis. When amino acid intake exceeds the body’s need for protein synthesis, excess amino acids are burned for energy or stored as fat. When blood glucose levels decrease, glucagon is secreted - the fasted state. Fats Store Energy -Chylomicrons - are lipoprotein &lipid complexes that are formed in the intestine to carry lipids into circulation; consist of cholesterol, triglycerides, phospholipids, and lipid-binding proteins called apoproteins, or apolipoproteinsOnce these lipid complexes begin to circulate through the blood, the enzyme lipoprotein lipase (lpl) bound to the capillary endothelium of muscles and adipose tissue converts the triglycerides to free fatty acids and glycerol. These molecules may be used for energy by most cells or reassembled into triglycerides for storage in adipose tissue. High-density lipoprotein (HDL) is sometimes called the “GOOD healthy cholesterol” because HDL is the lipoprotein involved in cholesterol transport out of the plasma. Lipoproteins that carry mostly cholesterol and phospholipids out of the plasma to the liver are HDLs. Low-density lipoprotein LDL-C is sometimes known as the “lethal cholesterol” because elevated concentrations of plasma LDL-C are associated with the development of atherosclerosis Dx: hypercholesterolemia (elevated plasma cholesterol levels); Lipoproteins that contain large amounts of cholesterol for transport to peripheral tissues are called LDLs. An effective way to lower plasma cholesterol levels is a drug that binds to bile acids and prevents them from being reabsorbed or a drug that adds plant sterols and stanols to the diet. The nutrient that yield the most energy per gram when metabolized are fats. Lipid Synthesis The body can make cholesterol from acetyl CoA through a series of reactions. Once the ring structure of cholesterol is synthesized, it is a fairly simple matter for the cell to change cholesterol into hormones and other steroids. Enzymes in the smooth endoplasmic reticulum and cytosol of cells are responsible for most lipid synthesis. For example, the phosphorylation steps that convert triglycerides into phospholipids take place in the smooth endoplasmic reticulum (ER). 22.5 Fasted-State Metabolism (REMEMBER THIS IS THE BROKEN DOWN STATE OF METABOLISM)– Review and understand how biomolecules are processed different organs during the fasted state. the signal for the body to shift from fed (absorptive) state to fasted (postabsorptive) state metabolism is when all nutrients from a meal have been digested, absorbed, and distributed to various cells, plasma concentrations of glucose begin to fall. Glucose homeostasis is achieved through catabolic pathways that convert glycogen, proteins, and fats into intermediates that can be used to make either glucose or ATP. Glycogen Converts to Glucose Liver glycogen can provide enough glucose to meet 4–5 hours of the body’s energy needs. In the fasted state, skeletal muscle glycogen can be metabolized to glucose, but not directly. Muscle cells, like most other cells, lack the enzyme that makes glucose from glucose 6-phosphate. Consequently, glucose 6-phosphate produced from glycogenolysis in skeletal muscle is metabolized to either pyruvate (aerobic conditions) or lactate (anaerobic conditions). Pyruvate and lactate are then transported to the liver, which uses them to make glucose via gluconeogenesis. PROTEINS CAN BE USED TO MAKE ATP muscle proteins can be broken down to provide energy, if fasted state goes on an extended time. Deamination - removal of the amino group from the amino acid, creates ammonia & organic acid (pyruvate, acetyl CoA, other intermediates of citric acid cycle). Organic acids enter pathways of aerobic metabolism for ATB production. Ammonia & Ammonium are toxic so liver cells convert them into urea (main nitrogenous waste of body and is excreted(you pee it out) by the kidneys). Before converting amino acids into intermediates for energy metabolism, they must first undergo DEAMINATION. If Glycogen storage is low ->plasma homeostasis threatened->protein can be used to make glucose (gluconeogenesis) LIPIDS STORE MORE ENERGY THAN GLUCOSE OR PROTEIN Lipolysis - the breakdown of fats and other lipids by hydrolysis to release fatty acids. Lipolysis occurs the fasted-state body needs to use stored energy (stored energy gets broken down). Beta-Oxidation (B-oxidation) - a metabolic process involving multiple steps by which fatty acid molecules are broken down to produce energy. In the fasted state, adipose tissue releases fatty acids and glycerol into the blood Glycerol goes to the liver and can be converted to glucose through gluconeogenesis. The fatty acids are taken up by many tissues and used for energy production. Ketone Bodies (Ketones) in the liver, if fatty acid breakdown produces acetyl CoA faster than the citric acid cycle can metabolize it, the excess acyl units become ketone bodies - source of energy for the brain in cases of prolonged starvation, when glucose is low The breath of people in ketosis has a fruity odor caused by acetone Ketogenic diet (Atkins/South Beach) - High fat & protein, low carb = shift of metabolism to BOxidation of fats & ketone production = rapid weight loss but d/t glycogen breakdown and water loss, no body fat reduction. Risks: Ketoacidosis, dehydration, electrolye loss, inadequate calcium & vit intake, gout, & kidney problems 22.6 Homeostatic Control of Metabolism – Review how the pancreas functions to be able to maintain fed/fasted state homeostasis by secreting hormones through variety of specialized endocrine cells. Amylin - a peptide hormone that is co-secreted with Insulin. It helps regulate glucose homeostasis following a meal by slowing digestion and absorption of carbohydrates. It also decreases food intake by a central effect on appetite, and it decreases secretion of glucagon. The Pancreas Secretes Insulin and Glucagon Islet of Langerhans - Small clusters of cells scattered throughout the body of the pancreas 4 Distinct Cell Type of Islet of Langerhands 1. Beta Cells - 3/4 of islet cells which produce insulin and peptide (amylin) 2. Alpha Cells - 20% secrete glucagon 3. D Cells - most remaining cells are somatostatin-secreting D Cells 4. PP Cells (or F Cells) - a few rare cells produce pancreatic Polypeptide >Both sympathetic and parasympathetic neurons terminate on the islets for nervous system to influence metabolism. The Insulin-to-Glucagon Ration Regulates Metabolism In Fed State - when the body is absorbing nutrients, insulin dominates, and the body undergoes net anabolism. Ingested glucose is used for energy production, and any excess is stored as glycogen or fat. Amino acids go primarily to protein synthesis. In the fasted state, metabolic regulation prevents low plasma glucose concentrations (hypoglycemia). When glucagon predominates, the liver uses glycogen and nonglucose intermediates to synthesize glucose for release into the blood shows plasma glucose, glucagon, and insulin concentrations before and after a meal. In a person with normal metabolism, fasting plasma glucose is maintained around 90 mg/dL of plasma, insulin secretion is low, and plasma glucagon levels are relatively high. After absorption of nutrients from a meal, plasma glucose rises. The increase in blood glucose inhibits glucagon secretion and stimulates insulin release. Insulin in turn promotes glucose transfer into cells. As a result, plasma glucose concentrations begin to fall back toward fasting levels shortly after each meal. Insulin secretion decreases along with the glucose, and glucagon secretion slowly begins to increase. Insulin Is the Dominant Hormone of the FED STATE Insulin - PEPTIDE HORMONE - synthesize as inactive prohormone and activated prior to secretion. Glucose - stimulus for insulin secretion but additional factor may enhance, amplify, or inhibit secretion: 1. Increased Plasma Glucose - glucose absorbed from small intestine reaches pancreatic beta cells where it is taken up by GLUT2 transporters. With more glucose available as substrate, ATP production increases and ATP-gated channels close. The cell depolarizes, voltage-gated channels open, and entry initiates exocytosis of insulin. 2. Increased Plasma Amino Acids - Increased plasma amino acid concentrations following a meal also trigger insulin secretion. 3. Feedforward effects of GI Hormones - The incretins (Gastric Inhibitory Peptide produced by cells in the jejunum and ileum) travel through the circulation to pancreatic beta cells and may reach them even before the first glucose is absorbed. The anticipatory release of insulin in response to these hormones prevents a sudden surge in plasma glucose concentrations when the meal is absorbed. Other GI hormones, such as CCK and gastrin, amplify insulin secretion. 4. Parasympathetic activity - to the GI tract and pancreas increases during and following a meal. Parasympathetic input to beta cells stimulates insulin secretion. 5. Sympathetic Activity - In times of stress, sympathetic input to the endocrine pancreas increases, reinforced by catecholamine release from the adrenal medulla (Tbl. 22.2). Epinephrine and norepinephrine inhibit insulin secretion and switch metabolism to gluconeogenesis to provide extra fuel for the nervous system and skeletal muscles. INSULIN IN A FED STATE The primary target tissues for insulin are the liver, adipose tissue, and skeletal muscles. The usual target cell response is increased glucose metabolism. In some target tissues, insulin also regulates the GLUT transporters. Other tissues, including the brain and transporting epithelia of the kidney and intestine, are insulinindependent—they do not require insulin for glucose uptake and metabolism. INSULIN PROMOTES ANABOLISM INSULIN’S CELLULAR MECHANISM OF ACTION Like other peptide hormones, insulin combines with a membrane receptor on its target cells. The insulin receptor has tyrosine kinase activity, which initiates complex intracellular cascades whose details are still not completely understood. The activated insulin receptor phosphorylates proteins that include a group known as the insulinreceptor substrates (IRS). These proteins act through complicated pathways to influence transport and cellular metabolism. The enzymes that regulate metabolic pathways may be inhibited or activated directly, or their synthesis may be influenced indirectly through transcription factors. Insulin lowers plasma glucose in four ways: 1. Insulin increases glucose transport into most, but not all, insulin-sensitive cells 2. Insulin enhances cellular utilization and storage of glucose 3. Insulin enhances utilization of amino acids 4. Insulin promotes fat synthesis >>>INSULIN SECRETION IS STIMULATED BY PARASYMPATHETIC NEURONS. >>>Insulin stimulates glycolysis and inhibits gluconeogenesis. >Summary, insulin is an anabolic hormone because it promotes glycogen, protein, and fat synthesis. When insulin is absent or deficient, cells go into catabolic metabolism. GLUCAGON IS DOMINANT IN THE FASTED STATE Glucagon, secreted by pancreatic alpha cells, is generally antagonistic to insulin in its effects on metabolism. The function of glucagon is to prevent hypoglycemia, so the primary stimulus for glucagon release is low plasma glucose concentration. ENDOCRINE RESPONSE TO HYPOGLYCEMIA FIG 22.18 The strong relationship between insulin secretion and glucagon inhibition has led to speculation that alpha cells are regulated by some factor linked to insulin rather than by plasma glucose concentrations directly. The liver is glucagon’s primary target tissue. Glucagon stimulates glycogenolysis and gluconeogenesis to increase glucose output. Glucagon release is also stimulated by plasma amino acids. This pathway prevents hypoglycemia after ingestion of a pure protein meal. If a meal contains protein but no carbohydrate, amino acids absorbed from the food cause insulin secretion. Even though no glucose has been absorbed, insulin-stimulated glucose uptake increases, and plasma glucose concentrations fall. Unless something counteracts this process, the brain’s fuel supply is threatened by hypoglycemia. Co-secretion of glucagon in this situation prevents hypoglycemia by stimulating hepatic glucose output. As a result, although only amino acids were ingested, both glucose and amino acids are made available to peripheral tissues. Diabetes Mellitus >Type 1: severe type of diabetes; condition of insulin deficiency resulting from beta cell destruction; >Type1 are prone to Ketoacidosis: If a type 1 DM patient ingest carbs, protein breakdown and ketone production would happen; Symptoms: Ketoacidosis, Thirst & Polydipsia, Hyperglycemia, Glucosuria. Fasted state metabolism: 1. Protein metabolism means muscle breaks down their proteins to provide a substrate for ATP production, amino acids are converted to pyruvate and lactate which leaves the muscle and transported to the liver. 2. Fat Metabolism: breakdown fat stores, fatty acids enter the blood for transport to the liver which uses B-Oxidation to breakdown fatty acids, but this organ is limited in its ability to send fatty acids through the citric acid cycle and the excess faty acids are converted to ketones. 3. Glucose Metabolism - absence of insulin, glucose remains in the blood, causing hyperglycemia. The liver, unable to metabolize this glucose, initiates fasted-state pathways of glycogenolysis and gluconeogenesis. These pathways produce additional glucose from glycogen, amino acids, and glycerol. When the liver dumps this glucose into the blood, hyperglycemia worsens. 4. Brain Metabolism - neurons in the brain’s satiety center are insulin sensitive. No insulin=satiety center unable to take up plasma glucose=starvation & allows the feeding center to increase food intake resulting in polyphagia. 5. Osmotic Diuresis and polyuria - osmotic diuresis is the loss of water in the urine due to unreabsorbed solutes 6. Dehydration can result from heat exhaustion and diabetes 7. Metabolic acidosis >Type 2: Known as insulin-resistant diabetes because in most patients, insulin levels in the blood are normal or even elevated initially. Later in the disease process, many Type 2 DM become insulin deficient and require insulin injections. >in DM2, insulin levels are frequently normal, yet the target cells are less sensitive to the effects of insulin, meaning target cells has problems in their signal transduction pathway. Metabolic Syndrome - is a combination of DM2, atherosclerosis, High BP Glucose tolerance test is a test used to measure the body’s insulin response to an ingested glucose load. 22.7 Regulation of Body Temperature - Review the mechanisms that allow the body to maintain its temperature, the types of heat loss, and the compensatory mechanisms that allow the body to return back to homeostasis after. Thermogenesis - temperature regulation in humans is linked to metabolic heat production Homeothermic - bodies regulate internal temperature within a narrow range (average body temp is 98.6F) (normal range 96-99.9F) Heat loss is promoted by sweating and dilation of cutaneous blood vessels. Heat Gain & Loss are Balanced Dynamic equilibrium depends on input and output. Heat input has 2 Components: 1. Internal Heat Production - heat from normal metabolism & heat released 2. External Heat Production - the environment through either radiation or conduction Radiant Heat Gain - radiant energy exposed to the sun or in front of a fire Conductive Heat Gain - transfer of heat between objects that are in contact with each other ex: skin, heating pad or the skin & hot water. 4 ways body loses heat: 1. Conductive Heat Loss - loss of body heat to a cooler object that is touching the body ex: icepack or cold stone bench; Direct transfer of heat energy from one object to another 2. Radiant Heat Loss - from the human body is estimated to account for half the heat lost from a body at rest in a normal room. Thermography - is a diagnostic imaging technique that measures radiant heat loss. 3. Convective Heat Loss - process in which heat is carried away by warm air rises from the body’s surface. Convection helps move warmed air away from the skin’s surface. Clothing, which traps air & prevents convective air currents, help retain heat close to the body. 4. Evaporative Heat Loss - takes place as water evaporates at the skin’s surface and in the respiratory tract. When water on the body evaporates, it removes heat from the body. Evaporative heat loss is affected by humidity of surrounding air: less evaporation occurs at higher humidities. BODY TEMPERATURE IS HOMEOSTATICALLY REGULATED Thermoneutral Zone - describes a range of temperatures of the immediate environment in which a standard healthy adult can maintain normal body temperature without needing to use energy above and beyond normal basal metabolic rate. >Humans are genetically adapted for life in warm climates. We thermoregulate by adapting to changing condition. Thermoregulation is the control of body temperature in the body. Thermoregulatory Centers - autonomic control of body temperature regulation is generally considered a function of thermoregulatory centers in the hypothalamus. Thermoreceptors - are Sensory Neurons located peripherally in the skin & in the anterior hypothalamus Heat loss from the body is promoted by dilation of blood vessels in the skin and by sweating. Heat gain is generated by shivering and possible by nonshivering thermogenesis. ALTERATIONS IN CUTANEOUS BLOOD FLOW CONSERVE OR RELEASE HEAT These blood vessels can pick up heat from the environment by convection and transfer it to the body core, or they can lose heat to the surrounding air. If core body temperature falls, the hypothalamus selectively activates sympathetic neurons innervating cutaneous arterioles. The arterioles constrict, increasing their resistance to blood flow and diverting blood to lower-resistance blood vessels in the interior of the body. This response keeps warmer core blood away from the cooler skin surface, thereby reducing heat loss. In warm temperatures, the opposite happens: Cutaneous arterioles dilate to increase blood flow near the skin surface and enhance heat loss. Only a small fraction of vasodilation results from the withdrawal of tonic sympathetic input. Active cutaneous vasodilation is mediated through sympathetic cholinergic neurons, specialized neurons that co-secrete acetylcholine and other molecules. Some proposed mediators of active vasodilation include nitric oxide, histamine, and prostaglandins. It remains unclear which vasodilator substances are most important in the thermoregulatory response. SWEAT CONTRIBUTES TO HEAT LOSS Heat loss is enhanced by evaporation of sweat. Humans have high concentration of sweat in: forehead, scalp, axillae, palms of hands, soles of feet. >Drink to replace lost of fluid volume Sweat production is regulated by cholinergic sympathetic neurons Because water evaporates rapidly in dry environments but slowly or not at all in humid ones, the body’s ability to withstand high temperatures is directly related to the relative humidity of the air. MOVEMENT & METABOLISM PRODUCE HEAT Heat production by the body falls in 2 Categories: 1. Unregulated heat production from voluntary muscle contraction & normal metabolic pathways 2. Regulated heat production for maintaining temperature homeostasis in low environment temperatures. >Regulated Heat Production divided further: 1. Shivering Thermogenesis - the body uses shivering (rhythmic tremors caused by skeletal muscle contraction) to generate heat. 2. Nonshivering Thermogenesis - is metabolic heat production by means other than shivering >Cold exposure increases heat production in brown adipose tissue (BAT) or BROWN FAT. The mechanism of brown fast heat production is mitochondrial uncoupling, energy flowing through the ETS is released as heat rather than being trapped in ATP. Mitochondrial uncoupling in response to cold is promoted by thyroid hormones and by increased sympathetic activity on B3 adrenergic receptors in brown fat. BROWN FAT >>Contains rich vascular supply >>it is found in infants >>is innervated by the sympathetic nervous system >>functions in nonshivering thermogenesis Fig.22.23 Homeostatic responses to environmental extremes THE BODY’S THERMOSTAT CAN BE RESET Examples of Physiological Variation to regulate body temperature: 1. Circadian Rhythm of body temperature 2. Menstrual Cycle Variations 3. Postmenopausal Hot Flashes - transient decrease in thermostat’s setpoint caused by absence of estrogen. When setpoint is lower, a room temp that had been previously comfortable suddenly feels too hot (sweating, cutaneous vasodilation) leads to flushing of the skin. 4. Fever - body’s normal immune response Pyrogens - toxins from bacteria and other pathogens trigger the release of pyrogen chemicals; fever reducing cytokines. Pyrogens may increase nonshivering thermogenesis causing body temp to rise. Enhances activity of WBC involved in immune response. Pyrogens is a chemical fever-producing cytokines that are part of the normal immunse response. Hyperthermia - Most common forms are Heat exhaustion & Heat stroke; body temp rises HIGH Heat Exhaustion - marked by severe dehydration and core body temp of 99.5-102.2F. Experience: muscle cramps, nausea, headache; pale & sweating profusely; occurs in people who are physically active in hot, humid climates to which they are not acclimatized; occurs in elderly with diminished thermoregulators. Heat Stroke - severe form of hyperthermia w/ HIGHER core temp; skin is flushed/dry. Immediate rapid cooling is important. Mortality is 50% Malignant Hyperthermia - body temp abnormally elevated Hypothermia - body temp falls low, dangerous condition; lose consciousness, O2 consumption decreases Remember that Hypothalamus regulates body temperature.