physiology exam 4
compare the differences between hyperplastic and hypertrophic adipose expansion, consider the consequences of these types of expansion
- hyperplastic: increased adipocyte NUMBER (increased adipogenesis from stem cells), linked to beneficial phenomena (decreased fatty acids release, por-inflammatory cytokine release, immune cell recruitment, hypoxia, fibrosis, improved insulin sensitivity) - hypertrophic: increased adipocyte SIZE, linked to harmful phenomena (increased fatty acid release, pro-inflammatory cytokine release, immune cell recruitment, hypoxia, fibrosis, impaired insulin sensitivity, causes stress to the cells)
describe how epinephrine, growth hormone, and cortisol work with glucagon to maintain blood glucose during the post absorptive state
-epinephrine raises BGL and mobilizes fat stores in adipose tissue, activates glycogenolysis in the liver and skeletal muscle, gluconeogensis in the liver, and lipolysis in adipose tissue -small increase in cortisol causes permissive effects on glucagon to raise BGL and on epinephrine to increase lipolysis. with stress, more cortisol is released. -growth hormone opposes the actions of insulin: increases lipolysis in adipose tissue, increases gluconeogenesis in the live, and reduces the ability of insulin to stimulate glucose uptake into insulin sensitive tissues. GH works with insulin to promote protein synthesis. GH tries to preserve protein mass while helping the body to switch from glucose to fat.
know how glucose is stored in adipose, skeletal muscle, and liver
-most cells in the body use glucose to make ATP -skeletal muscle uses glucose to make ATP and store gylcogen -adipose cells use glucose to make ATP to make triglycerides -glucose enters liver cells to store as glycogen and to convert to triglycerides
know how lipids are stored in adipose, skeletal muscle, and liver
-triglycerides and cholesterol that we eat is packaged into chylomicrons in enterocytes and absorbed into the lymph. eventually chylomicrons deliver TGL to adipose -extra glucose and amino acids are converted into TGLS in the liver, packaged into VLDLs and sent to adipose cells via the blood
identify the layers of the gut wall and describe the function of each layer
1. mucosa: inner most layer, created from epithelial cells, lamina propria, and muscularis mucosae (smooth muscle). modification increase surface area (folds in stomal, villi, gastric glands, crypts, and submucosal glands. exposed to the external environment 2. submucosa: connective tissue, contains submucosal plexus of the enteric nervous system, composed of neurons 3. muscularis externa: consists of two layers of smooth muscle, contains myenteric plexus of the enteric nervous system (neurons) 1st layer: circular, 2nd layer: longitudinal 4. serosa: outer most layer, continuation of the peritoneal membrane, which forms sheets of mesentery (connects GI tract to the rest of body)
compare the brown adipose tissue (BAT) between infants and adult humans. consider both similarities and differences in development and function
BAT is inversely associated with body size in mammals. the interscapular BAT can be found in all infants, but it regresses and is absent in adults. perirenal BAT is also present in human infants, but its prevalence decreases with age. thes BAT depots form during embryonic development , before other white/brown depots. BAT is adults develops postnatally, forming a "biological scarf". cervical, supraclavical, and axillary areas have high volume of BAT. some BATs are paravertebral and perirenal
explain why adipose is now regarded as an organ, not just a tissue
an organ is defined by the presence of 2 or more distinct tissues that work together for 1 common function. Adipose has several cell types that interact to coordinate the metabolic functions. It is vascularized by blood and lymphatic vessels, innervated by sympathetic and sensory nerves, immune cells, fibroblasts, and mesothelial cells.
compare and contrast the four mechanisms for heat loss
convection: the process whereby conductive heat loss or gain is aided by movement of the air or water next to the body radiation: the process by which the surface of all objects (including our body) constantly emit heat in the form of electromagnetic waves evaporation: of the water from the skin and membranes lining the respiratory tract conduction: the loss or gain of thermal energy through direct contact with cooler or warmer substances
from an energy balance point of view, what are the ways to reduce body weight?
decrease food intake and absorption, continue basal metabolism, increase physical activity and thermogenesis
there are many white adipose depots associated with other tissues. Can you name a few such fat depots and describe their function?
dermal tissue, heart tissue, joint tissue, mammary tissue, bone marrow, and muscle tissue. skin, mammary gland, and bone marrow: modulation of tissue homeostasis. microenvironement for tissue stem cells. skin, intramuscular: signaling for wound repair joints, feet and palms: biomechanical, shock absorbance intermuscular: metabolism, lipid storage heart, mammary gland: lipid feeding skin, intestine: innate immunity, antimicrobial cytokines
overview of the four major processes of the GI system
digestion: chemical and mechanical breakdown of food into absorbable units. happens in stomach and small intestine absorption: movement of material from GI lumen to ECF. occurs between small intestine and capillaries. motility: movement of material through the GI tract as a result of muscle contraction secretion: movement of material from cells into the lumen or ECF (reverse of absorption) occurs between the small intestine and capillaries.
compare and contrast the sequences of events leading to a fever and to hyperthermia during exercise
during exercise, heat production temporarily exceeds heat loss, which results in net heat storage. the rate of heat storage is highest initially and falls to zero in the new steady state. as body core temperature rises away from set-point, the error signal gradually increases. in the new steady state, the error signal is maximal and sustained. during fever, net heat storage can occur because of either reduced heat loss or increased heat production. as in exercise, the rate of heat storage is highest initially. as body core temperature rises, it approaches the new elevated set point. thus, the error signal is initially maximal and gradually decreases to zero in the new steady state
describe the actions of glucagon on the liver and the regulation of glucagon secretion
glucagon is a peptide hormone that is secreted from the alpha cells in the pancreas, primarily targeting the liver. the secretion of glucagon is antagonistic to insulin when regulating the blood glucose levels. glucose enters alpha cells through insulin-independent GLUT1 transporter. promotes glycogenolysis and gluconeogenesis in the liver, which causes blood glucose levels to rise. if blood glucose levels continue to rise, hyperglycemia inhibits the release of glucagon.
describe the journey of glucose, lipids, amino acids from gut to liver to peripheral cells, and where they are used and stored
glucose and amino acids are absorbed into capillaries of the villus -> glucose and amino acids travel to the liver via the hepatic portal vein. intestinal cells package TGL into chylomicrons -> exocytosis in the lymph lacteal -> lymphatics eventually empty into the venous system -> TGL delivered to the adipose tissue
explain how incretin hormones (like GLP-1) lowers blood glucose after a meal
glucose in the lumen of the small intestine stimulates secretion of incretins, incretins enhance glucose-dependent insulin secretion or inhibits the secretion of glucagon, which then lowers the blood glucose
describe the natural history of pancreatic beta cells dysfunction in type 2 diabetes
in type 2 diabetes, beta cells fail to produce sufficient insulin. this can be caused by naturally small beta cell mass, defective beta cell proliferation, beta cell death, ER or oxidative stress, differentiation, loss of identity, or transdifferentiation
discuss how obesity and insulin resistance complicates type 2 diabetes
insulin binds to its receptor but phosphorylation events in the intracellular cascade do not occur and GLUT4 is not inserted into the membrane. GLUT4 expression is also down-regulated. fat is stored in inappropriate sites such as the muscle, liver, and pancreas. a small weight loss removes TGL from non-adipose tissue.
explain how insulin promotes glucose uptake in adipose and skeletal muscle
insulin binds to receptor and triggers signaling transduction pathways that influence targets (plasma membrane transport protein, GLUT4), more GLUT4 in the plasma membrane causes a greater rate of glucose diffusion from the extracellular fluid into the cell by facilitated diffusion.
describe in sequence what happens when leptin is secreted from the white adipose organ. list the reasons why leptin failed to treat obesity in clinic
leptin acts on neurons in the hypothalamus to supress food intake while increasing energy expenditure, in order to restore energy homeostasis. congenital leptin deficiency is a rare disorder, leptin resistance is observed in obese individuals. changing leptin levels signal the switch between starvation and energy sufficiency. leptin was ineffective in improving insulin sensitivity and glycemic control in obese individuals with T2D. reverses insulin resistance and improves glycemic control in patients with lipodystrophy.
explain the relationship between increased fat breakdown (lipolysis and beta-oxidation) and the production of ketones
lipid triglycerides are hydrolyzed into a glycerol and three fatty acids. it is used to mobilize stored energy during fasting of exercise, and usually occurs in fat adipocytes.
describe the benefits of having the white adipose organ to store energy (consider what happens when the adipose organ is dystrophic)
lipids are the most concentrated form of energy storage and the major expendable fuel source (weighs 14kg and has 9.4 kcal/g, which is 131,600 kcal of energy). fat storage serves as a reserve for unanticipated shortfalls in food supply.
describe the sequence of events that happen to thermogenic adipose organs when animals are exposed to cold temperature
norepinephrine secreted by activated sympathetic neuron binds to beta-adrenergic receptors, increasing UCP1 expression, glucose uptake, lipolysis to generate fatty acids. In brown adipose tissue, UCP1 catalyzes the re-entry of proton into the matrix to generate heat, thus uncoupling the mitochondrial respiratory chain.
describe glucose sparing and explain how it supports the energy needs of the body during the postabsorptive state
the glucose produced in the liver and kidneys is released into the blood, but its utilization for energy is greatly decreased in muscle and other nonneural tissues. Lipolysis releases adipose-tissue fatty acids into the blood, and the oxidation of these fatty acids by most cells and of ketones produced from them by the liver provides most of the body's energy supply. the brain continues to use glucose but also starts using ketones as they build up in the blood.
explain how the glycogenesis and gluconeogenesis by the liver maintains glucose for brain function during the post absorptive state
the liver breaks down glycogen and synthesizes new glucose form lactate, pyruvate, glycerol, and some amino acids (gluconeogenesis) that can be used by the brain. Most cells use fatty acids and ketones for energy so that glucose can be spared for the brain.
thermoneutral zone
the range of ambient temperatures where the body can maintain its core temperature with minimal metabolic regulation. at TNZ, approximately 22 to 30 degC in humans, thermoregulation is solely through dry heat loss (radiation and conduction). below TNZ, maximal vasoconstriction, heat production through shivering and nonshivering thermogenesis. above TNZ, evaporation is the sole mechanism for heat loss, determined by humidity and maximal sweating rate
what are the dominant mechanisms for thermoregulation in temperatures in, above, and below the thermoneutral zone?
the skin functions as a regulator of heat exchange. vasoconstriction reduces blood flow and helps retain heat. vasodilation increases blood flow to the skin and helps the animal lose some of its extra heat to the environment. reducing surface area (curling up/hunching shoulders), insulation (feather, hair, fur, clothing), and seeking warm temperature all reduce heat loss mechanisms like sweating and panting increase evaporative cooling, dependent on water vapor pressure gradient, not temperature gradient between skin and the environment.
current FDA-approved medicines all target food intake and absorption. based on the equation of energy balance, can you identify some future directions for developing anti-obesity therapies?
therapies that involve an increase in physical activity or that simulate exercise, caloric restriction mimetics, recruitment and activation of thermogenic adipocytes
compare and contrast the three major forms of diabetes: type 1, type 2, and gestational diabetes
type 1: insulin deficiency, immune-medicated type 2: obesity, insulin-resistant, and aging gestational: glucose intolerance during 3rd trimester of pregnancy
use the "set point" theory to explain why it could be difficult to lose weight through diet or exercise
when our body weight stays constant, our total energy expenditure is in balance with our intake of calories and is dependent on the mass of tissues that expend the most calories (fat free mass). this orderly relationship is not altered by obesity that occurs spontaneously, but when either obesity or weight loss is deliberately pursued (in an experiment or diet program). changes in energy expenditure occur as our internal control system strives to restore the level of fat storage (set point). possible solution to long-term weight control: to increase TEE while reducing calorie intake
compare the fundamental differences between white, beige, and brown adipocytes. consider these differences at the morphological as well as functional levels
white: single large lipid droplet, few mitochondria, vascularized and innervated, no UCP1 protein, stores excess energy (TGL), endocrine function. uni-locular brown: multiple small lipid droplets, rich in mitochondria, densely vascularized and innervated, uncoupling protein 1 (UCP1), dissipates chemical energy (non-shivering thermogenesis), endocrine function. multi-locular. beige: positive UCP1 expression, medium mitochondrial density, multi-locular. adipocytes sporadically reside in subcutaneous white adipose tissue depots.
