Physiology GIT etc. PDF

G.I.T Introduction Carnivores: short simple GIT meat has high energy density = easily absorbed Herbivores: ruminants & hind gut fermenters 4 stomach fermentation Make use of ca...

G.I.T Introduction Carnivores: short simple GIT meat has high energy density = easily absorbed Herbivores: ruminants & hind gut fermenters 4 stomach fermentation Make use of carbs in plants which can only be broken down by digestive enzymes Energy source (fermentation) = population of GIT microbes break down the bonds * largest Omnivores: ability to vary diet Large intest. slightly longer GIT than carnivores Forms barrier against the Contains epithelial cells environment only starts in small intestine (absorption) damage could allow Stops in Large intestine bacteria to enter Tight junction circulation Another example of a portal system Defence of GIT Epithelial cells constantly 1. Lymphatic system replaced new cells are formed in large amount of lymphatic crypts drainage Migrate up the villus Lymph nodes in mesentery Slough off the top have a bunch of macrophages Lifespan. 2-3 days 2. By the liver Inner portion hepatic portal circulation Prevents bacteria in systemic circulation Connective tissue holding Goes to liver with tons of mucosa together macrophages = 1st line of cellular defense Outer layer Helps shorten tube & close lumen circular smooth muscle = decrease diameter of lumen Longitudinal smooth muscle Two muscles NB for peristalsis & mixing  Accessory organs Salivary glands: moisten food & begin Nerve supply : Enteric nervous system (how it is G.I.T chemical digestion liver: creates bile for fat digestion switched on & off) Gallbladder: stores bile Pancreas: secretes pancreatic juice to help via 2 ways : digestion of protein & carbs Neural & hormonal regulation - Enteric nervous system Stimuli from other parts of the body long reflexes : CNS involved (vision, taste & smell) Short reflexes: enteric system auto regulation Mostly regulated by negative feedback loops = stimulus, causing reaction —> reaction inhibits further reaction Different sensors : chemical, osmotic, pH & stretch CNS (Autonomic parasympathetic system) Long reflex also stimulate accessory organs Salivary glands Pancreas & liver digestive enzyme = bile Sensory cells Smooth muscle (contract) Nerve plexuses Or gland (secrete) wall of gastrointestinal tract Brain involved Stimuli Long reflex lumen of digestive tract E.g : stretch reflex if too much food or opening of chemical channels Short reflex tract Lumen of digestive How each component of intestine regulated : Regulation of appetite Carbohydrates Insoluble carbohydrates Controlled by centres in the hypothalamus Soluble carbohydrates Structural component of grasses negative feedback Chains of monomers chains of monomer molecules - polymers cellulose (from hay) & fructans (green grass) Receives information from: Starch or glycogen Degree of gastrointestinal filling: Bonds = B-glycosidic - can’t be digested by animal Bonds = a-glycosidic - can be digested by enzyme enzymes stretch sensitive mechanoreceptors produced by animals require digestion by bacteria in an anaerobic Cholecystokinin = hormone releases from full gut environment- fermentation in hind gut Absorbed as monomers in small intestine Absorbed as Volatile Fatty Acids (product of Hormone levels glucose, fructose & galactose fermentation, animals form of nutrients) insulin = released in response to high blood glucose, tell hypo to stop eating Leptin - produced by adipose tissue External factors Proteins environmental temp - cold eat more Deficiencies may increase certain foods = Pica = Organic nutrients Chains of peptides - polypeptides some herbivores eat bones due to calcium deficiency digested by enzymes produced in the or dogs eat grass stomach, small intestine and pancreas Absorbed as short peptide chains or amino ·· acids in small intestine Fats e · Get to liver via whole different route Then absorbed by lymphatic system Fats : emulsified by bile carbs & proteins go into circulatory system triglycerides, phospholipid’s & cholesterol Digested by enzymes produced in pancreas Bile = produced in liver & stored in gall bladder Absorbed as monoglycerides & fatty acids  2. Secretion of digestive juices 1. Mechanical processing Digestive enzymes are produced by : Chewing - mastication (mouth) specialised epithelial cells - stomach & small intestine external force = jaw muscles & teeth Salivary glands purpose: Increases surface area for enzyme action Pancreas Liver Mixing of gut content (chyme - stomach & small intestine) external force = muscle contraction of smooth muscle Mucus is secreted along the length of the GIT Purpose : exposes chyme to enzymes & to lumen wall goblet cells in lining of epithelial cells Four digestive processes 3. Enzymatic breakdown of organic nutrients 3 basic types of nutrients 4. Absorption from the digestive tract 1. Non structural carbohydrates 2. Proteins First place happens in small intestine 3. Lipids small molecules need to be transported from lumen of GIT —> blood or lymph capillaries Structural carbohydrates? generally, energy rich molecules are large - so must be broken down into monomers or smaller polymers for absorption Saliva The stomach Components: Secreted from salivary glands Major functions: storage Epithelial cells produce mucus small intestine can’t stretch much so can only take small protection from acid, no mucus = acid in Functions: quantities. So the stomach stores the food and feeds small stomach will burn epithelial cells quantities of chyme into the small intestine Lubrication Pits in the stomach wall contain secretory cells Mucins - lubrication & softening food in Other functions parietal cells = hydrochloric acid which creates order for us to taste 1. Hydrochloric acid production : aids digestion, kills bacteria pH Taste requires particles in solution 2. Pepsin : secreted as pepsinogen (inactive). Proteolytic Chief cells = pepsinogen (inactive pepsin to enzyme (digestive protein) protect stomach wall, only active once in lumen) Antibacterial effect 3. Mixing & minor mechanical breakdown of chyme Endocrine cells produce hormones (Gastrin & histamine —> no functional role in digestion but Enzymatic digestion primary stimulatory role in HCl) salivary amylase starts process with carbs in certain species & pH regulation Saliva & stomach I saliva = basic Goes basic —> acidic in stomach Thermoregulation (panting) Extra - stomach When stomach contains liquid only : gastric emptying increases Regulation of HCl in stomach When stomach contains solid bulky food: gastric emptying decreases 3 mechanisms: Large particles are retained until they can be broken down nervous system Histamine Bulky chyme = slow transit Gastrin Liquid chyme = fast transit If 1 fails there’s a back up Fat also decreases the rate of gastric emptying Pancreas Hormonal regulation of pancreatic HCO3 secretion Activation of pancreatic enzymes duodenum 1. ↑ Located between stomach & descending Has an endocrine & exocrine function Endocrine —> insulin & glucagon 2. Exocrine —> production of pancreatic juice, HCO3, enzymes activated by secretin Buffer acidic chyme coming in How is secretion of enzyme regulated? hormonal regulation of pancreatic enzyme secretion & gallbladder contraction Peptides & FA in duodenum stimulate release of Enzymes are secreted as inactive pro- enzymes protects the pancreas from auto-digestion Trypsin is a protease that is responsible for activation of all the other proteolytic enzymes = secreted as inactive trypsinogen & activated by : enteropeptidase —> produced by small intestinal epithelial cells CCK CCK stimulates release of enzymes & bile Trypsin - self activating cycle (autocatalysis) Exocrine Stops with reduction of CCK Pancreatic juice realised into —> proximal duodenum @ major + minor duodenal papillae High bicarbonate levels = basic environment neutralises acidic content preventing duodenal injury e · Hind gut fermenters require = more basic pH Pancreatic enzymes activated in · alkaline pH Pancreatic juice contains enzymes - produced by acinar cells in pancrease Lipase —> breaks down lipids · Amylase —> breaks down starch · o t Proteases —> breakdown proteins N Liver Bile production & secretion Functions: Produced by hepatocytes (liver cells) 1. Production of bile - lipid digestion secreted into small canals between hepatocytes called bile 2. Processing of substances absorbed from the canaliculi GIT Canaliculi summate into gradually larger canals 3. Regulating the concentration of substances End point = common bile duct which is shared with the in the blood pancreatic duct 4. Converts & inactivates substances (toxins & hormones) Sphincter of Oddi guards entrance of common bile duct into 5. Excretes or transforms substances for duodenum excretion when closed bile backs up into the gall bladder (not in the 6. Produces plasma proteins - albumin horse!) 7. Produces clotting factors Horse don’t have gallbladders : constantly eating as they’re constantly releasing bile Trigger : food —> triggers CCK —> gall bladder contracts —> bile released. Bile acids Produced from cholesterol joined together with an amino acid molecule to form bile salts Bile salts Necessary for the intestinal digestion of fat Amino acid = hydrophilic end Steroid or bile salt = hydrophobic end Hydrophobic side binds to fat (inside), hydrophilic side faces the chyme (outside) Bile = breaks large fat into small droplets Bile = recycled Forms micelles (small fat droplets) Bile salts = reabsorbed by an active process @ end of larger surface area : important because pancreatic small intestine lipase works better with small droplets returned to liver via the hepatic portal vein Greater lipase action Re-secreted Entero-hepatic circulation  Liver Go to vena cava & continue venous circulation Oxygen F Hepatocytes - Hepatic portal system 2. Takes nutrients from G.I.T —> nutrient Brings in nutrient rich blood but not oxygen 1. Blood from abdominal goes blood delivered to hepatocytes bile reabsorbed here into hepatic vein & not the inferior vena cava (oxygen to 3, After processing, blood is delivered G.I.T) to the inferior vena cava  Secretion Motility Filling of the stomach induces intestinal motility & secretion Absorption The muscular wall of the small intestine is responsible for: In addition to pancreatic & biliary secretion, the crypt cells @ base S.I has large reserve capacity mixing of the content —> NB to bring food of the villi produce: most nutrients are absorbed into contact with lumen 1. Intestinal juice (water, bicarbonate and mucus) long before the end of the SI Ensuring the luminal content comes in 2. Enzymes (not released into the lumen, remain bound to About 50% of bowel can be contact with the epithelial cells epithelial cells & function in the luminal membrane of the removed. Short bowel Transport of the chyme - in a direction away epithelial cells (enteropeptidase) syndrome = if you remove from the mouth too much, not enough left for absorption to happen Types of contraction: segmentation : mixing Peristalsis: movement from 1 end to the other Small intestine 3 structural features that increase surface area for absorption: 1. Numerous mucosal folds 2. Villi 3. Microvilli (unique to S.I) Absorption mechanisms: Simple diffusion : no energy required water soluble & lipid soluble substances · Large water soluble substances —> facilitated diffusion (requires carrier proteins but no energy required) Small portion of osmotic regulation dehydration = not enough water = Active transport : carrier proteins hard stool anything moved against the concentration gradient - active Exocytosis & endocytosis: bulk transport engulf molecules  Protein Carbohydrates 2. Membranous phase - tri & di peptides + amino acids Exogenous protein : membrane bound enzymes Digestion: protein from diet Large number of enzymes required for protein long rows of repeated monosaccharide units breakdown, peptide bonds differ slightly Endogenous protein: digestive juices, sloughed epithelial cells, Soluble carbs : a-glycosidic bonds: broken down by mammalian mucus Absorption: digestive enzymes all reabsorbed - no waste small intestine Absorbed as amino acids, dipeptides & tripeptides Digestion: small peptides broken down into amino acids in Insoluble carbs: b-glycosidic bonds broken down by bacterial 1. Luminal phase - short peptide chains epithelial cells fermentation Stomach —> pepsin, minor role on protein digestion Absorbed by secondary active transport hind gut/rumen Small intestine —> pancreatic proteases, major role in Small amounts of protein are absorbed by protein digestion transcytosis - potential to cause allergic reactions Degradation: Transported to the liver, take up by hepatocytes Before they can be absorbed they must be broken down into monomers 1. Luminal phase (degradation of carbs) starch & glycogen digested by amylase into compounds —> common product : maltose Salivary amylase = low activity Small intestine Water is constantly absorbed by villi Pancreatic Amylase = highly active Function : to maintain a liquid chyme water is 2. Membranous phase constantly secreted by crypt cells short carbohydrate chains broken down into Water monosaccharides by enzymes in the membranes of epithelial Small intestine absorbs majority of water cells (specific to the carbohydrates) Water always follows an somatic gradient Enzymes may alter with age (lactase is less active in adult Where do we get H2O from? animals) food & fluid we eat/drink Water will follow the absorption of certain substances: Saliva sodium Absorption Gastric juice & pancreatic juice Glucose absorption of glucose & galactose is linked to absorption of bile Amino acids Na+, against concentration gradient (active) Intestinal juice Volatile fatty acids Absorbed glucose is processed by the liver —> glycogen  Absorption Small intestine Micelles are so small that they can enter the spaces between the Microvilli fatty acids & monoglycerides are fat soluble so diffuse out of micelles & through epithelial membrane Fat Once in the epithelial cell they reform into triglycerides Types: triglycerides, cholesterol & phospholipids don’t travel well on its own —> needs a carrier protein : chylomicrons (type of lipoprotein) triglycerides= 1 monoglyceride & 2 fatty acids Triglycerides come together to form chylomicrons Lipase : from pancreas also contain cholesterol two fatty acids ids are split from the triglyceride Covered in a protein coat Water soluble = on,h able to act on surface between fat release into the interstitial fluid by exocytosis & water Too large to enter capillaries Bile salts: from liver Transported by lymph to central circulation emulsified fat Increase SA for lipase action Aided by mixing action of segmental movements ( form micelles with degraded monoglycerides & free fatty acids —> absorbed) Functions: Horse (or herbivores) Absorption of the leftovers that small intestine didn’t do Horse : modified for microbial digestion so they can eat water insoluble carbs Vitamins fermentation breaks b-glycosidic bonds in anaerobic Large intestine Ions conditions Breakdown of cellulose Microbial digestion of fibre Volatile fatty acids are produced by microbes & absorbed by Has : large colon smooth mucosa, so no villi fermentation takes place at a slightly basic pH Intro for energy utilisation Absorptive state S Glucose Energy in find absorbed in form of : Hepatocytes : process amino acids, monosaccharides & glucose, amino acids & fatty acids triglycerides from digestive tract (anabolic process, Absorbed from intestines - hepatic adding molecules together) portal system —> liver Energy stored as: adjusts concentration of incoming nutrients used as energy in hepatocytes glycogen : carbs store —> liver store & Then distribute to tissue Some stored as hepatic glycogen muscle store Surplus stored as glycogen & fat (also muscle glycogen) Triglycerides: fat stores —> adipose tissue Synthesis of triglycerides in: hepatocytes Adipocytes Summary: Cells utilise energy from nutrients from GIT directly Hepatocytes produce glycogen & lipids for Amino acids immediate use Excess stored as lipids & glycogen Absorbed from GIT - enterohepatic circulation Net synthesis of proteins occur in all cells processed by hepatocytes (anabolism) Utilisation of organic nutrients Makes non-essential amino acids Keto acids go into gluconeogenesis (Absorptive phase) NH4 broken up into Urea —> excreted via kidney Lipoproteins Chylomicrons formed by epithelium in GIT Function: transport dietary lipids Lipids Uber driver for triglycerides HDL M produced in liver Dietary lipid from intestines into lymphatics VLDL, LDL Lipids produce in liver from glucose N Function: collects cholesterol leaking from 60% triglycerides, ret phospholipids & cholesterol cells & transports it back to liver triglycerides: provide energy Formed in liver Excreted as bile Cholesterol: cell membrane & bile Function : transport fats to the tissues “Good cholesterol” Phospholipid: cell membrane, enzymes etc “Bad cholesterol”  Glucose Terms Glycogenolysis Plasma concentration stay relatively stable by: Glygogenolysis - breakdown of glycogen to glucose mobilisation of glycogen from liver (glycogenolysis) glycolysis - breakdown of glucose to Pyruvate Plasma concentration of glucose drops Synthesis of glucose by non-carb sources (gluconeogenesis) Gluconeogenesis - building glucose from non carb sources liver starts mobilising its Utilisation of lipids as energy (glucose sparing) Glucose sparing - tissue using lipids to spare glucose glycogen reserve Glycogen reserve = small, can only maintain plasma concentration for a few hours Glucose sparing Tissue gradually convert to utilise lipids as main energy Gluconeogenesis Post absorptive state source nutrients no longer absorbed triglycerides broken down to fatty acids & Glucose produced from non-carbohydrate sources from intestines glycerol use amino acids, glycerol, lactate & Pyruvate Body stores are used Glycerol used for gluconeogenesis Amino acids used come from muscle protein (Alanine) Catabolic process Fatty acids oxidised to water & carbon dioxide Propionic acid (VFA) used as a precursor releasing energy Ketones synthesised in liver Summary mobilise energy stores Fatty acids mobilised by degradation of stored fats Glucose formed by degrading glycogen (glycogenolysis) & synthesis of new glucose from amino acids (gluconeogenesis)  T Introduction How it’s regulated: Insulin & glucagon from pancreas (endocrine part) Hormones from GIT Autonomic nervous system Glucocorticoids from adrenal gland (cortisol) Autonomic nervous system Glucagon Regulation of metabolism Sympathetic nerves stimulates glycogenolysis but not gluconeogenesis why: because glycogenolysis is a fast process whereas gluconeogenesis takes time Also mobilise fatty acids Glucocorticoids Cortisol secreted by adrenal gland in response to stress not important during normal metabolism but during periods of stress Cortisol stimulates gluconeogenesis & lipid mobilisation from adipose tissue  Types of glands Hormones Where they function 1. Endocrine: secretes product into blood or interstitial space (thyroid & Chemical messengers adrenal glands, pituitary) regulate metabolic processes in a target cell Classic hormones (endocrine) 2. Exocrine: secrete product into duct system (salivary glands) Target cell possess receptors specific to the carried by blood to target cell 3. Paracrine - hormones diffuse a short distance to target cells hormone (juxtaglomerular apparatus) Endocrine system compromises of all tissues that Local hormone 4. Autocrine: secretions affects same cell (mammillary gland, WBC) secrete hormones diffuse through interstitial fluid to Only a small amount of hormones requires to target organ Certain glands have both exocrine & endocrine function effect a response in target cell (due to Paracrine - affects neighbouring cell pancreas & testis amplification) Autocrine - affects cell from which its Certain organs with other main functions also possess endocrine cells secreted (cancer cells, stimulates kidneys (production of erythropoietin), GIT, liver mitosis of the cell) Neurohormones Endocrinology Water soluble hormones secreted by neurons Transported in blood Protein & peptide hormones unable to penetrate cell membrane Tropic hormones = regulate the secretion of Question Binds receptor in cell membrane other hormones & stimulate the growth of Alter activity of pre-existing proteins (fast process target glands Explain how a hormones composition can affect its mechanism of compared to lipid soluble molecules but slower than action and hence its function. Use an example to illustrate this nervous system) Made & stored in vesicles Answer : Lipid soluble hormones Composition of hormone will confer certain properties to that hormone Steroid hormones & fatty acid compounds made of : protein or steroid penetrate cell membrane makes it water soluble or lipid soluble Binds intracellular receptors Solubility will determine if it works with receptor on cell Alters gene transcription - synthesis membrane or on receptor inside the cells of proteins —> slow process bc Works on protein that has already been made / new protein protein needs to be made from scratch is made through DNA transcription Secreted by diffusion as soon as Will determine speed or response (fast or slow) made, not stored  Endocrine control Explain how the secretion of hormones is regulated by the autonomic nervous system Endocrine system : largely involved in the maintenance of homeostasis Autonomic nervous system functions through the negative feedback = maintains the effect of the hypothalamus target cells around a set point hypothalamus secretes releasing hormones affecting cascade of reactions Negative feedback Regulated through negative feedback loops/ stops hypothalamic secretions Def: the effect of a certain hormone may inhibit further production of that hormone E.g : increase blood glucose = increase insulin = Hypothalamus decrease blood glucose = decrease insulin The activities of both the autonomic nervous system & the Positive feedback endocrine system are coordinated by the hypothalamus because: Used for amplification of signal it serves to link the endocrine system with the nervous Aiming towards an end point —> does not maintain system homeostasis Receives information about the bodies internal & E.g : clotting cascade external environments via sensory neurons Not used in endocrine system Regulates secretion of hormones & autonomic nervous system activity Autonomic system = fast, endocrine system = slow Posterior pituitary Neuro endocrine cells in hypothalamus make & secret Long neuron’s extend from the hypothalamus into the neurohormones which are transported to either posterior pituitary 1. Posterior pituitary = via axons 2. Anterior pituitary = via hypothalamic-pituitary portal Produce: system oxytocin & ADH Produced in hypothalamus & secreted from the pituitary gland into the circulatory system ADH & control of Osmolarity ADH increases the permeability of the distal convoluted Oxytocin from post-pituitary tubules and collecting ducts to water in the kidney increased aquaporins Causes smooth muscle contraction in: uterus ADH secretion is also activated by the rennin- Mammary gland duct —> release milk angiotensin system which also goes to the hypothalamus Important during labor & lactation  Anterior pituitary gland Hypothalamus Hypothalamus secrets ‘releasing hormones’ that travel via a Anterior pituitary gland portal system to the pituitary gland in the pituitary they stimulate release of hormones - system Produces large amounts of hormones of amplification E.g growth hormone releasing hormone The pituitary hormones travel to target cells in other glands: Secretes ‘inhibiting hormones’ that travel via a portal system to target cells further amplify the signal the pituitary gland Act on final target organs in the pituitary they inhibit the release of hormones E.g Somatostatin = decreases growth hormone, decreases Each hormone released has a negative feedback thyroid stimulating hormone effect on the glands preceding its secretion posterior pituitary lobes verview  Endocrine Glands Stimulated by decreased blood calcium levels Located in the thalamus secretes PTH monitors circadian rhythms Raises blood calcium levels Produces melatonin that plays a role in Located on either side of the trachea below larynx Activates Vitamin D3 in the kidney biological rhythm e.g oestrus cycle (calcitriol) —> increased absorption of Darkness stimulates melatonin production Function: controls metabolic rate calcium from intestine Light inhibits melatonin secretion Hypothalamus releases thyrotropin releasing hormone (TRH) TRH stimulates pituitary gland to secret thyroid Hyperthyroidism stimulating hormone (TSH) TSH stimulates thyroid gland to secrete thyroid More common in cats hormones typical tumour of thyroid gland Increased thyroid hormones triggers negative feedback loop and TRH stops getting released - */ Hormone levels : thyroid = high, TSH = low (negative feedback loop still good & Thyroid hormones: working Main effect: increase metabolism increase oxygen consumption Clinical signs: Increase heat generation weight loss affects gonads, growth & sympathetic nervous system Increased appetite Aggression Thyroid also stimulated by increased blood calcium: Poor coat condition · p Secrete calcitonin (calcium metabolism) Inhibits oesteoclasts Hypothyroidism Low thyroid levels Clinical signs: more common in dogs heat seeking (due to slow metabolic & heat production rates) Primary hypothyroidism due to autoimmune destruction of thyroid Sluggish gland (low T4 & high TSH due to negative feedback loop) Overweight despite poor appetite Secondary hypothyroidism due to decreased synthesis of TRH Patchy alopecia or TSH or both (pituitary problem) —> both T4 & TSH low Skin infections  Zona Glomerulosa: Mineralocorticoid Adrenal glands have a cortex & a medulla Secretion of aldosterone regulated by Renin-Angiotensin-Aldosterone system (RAAS) Zona fasciculata s Cortical hormones - steroid hormones Extracellular concentration of potassium cortisol = the bodies own cortisone Cortisol = essential for life (all nucleotide cells have Aldosterone = re absorption of Na+ in the kidney Function: increase absorption of sodium and water in the distal cortisol receptors) convoluted tubule & collecting duct Functions: Medullary hormones - catecholamines stress : high levels of glucocorticoids = increase Adrenalin & noradrenaline = sympathetic nervous system Catecholamines blood glucose Dopamine Carbohydrate metabolism: stimulate hepatic Neurohormone in adrenal medulla because axon synapsing on Function: last short period of time gluconeogenesis cell typical sympathetic Protein metabolism: stimulates breakdown of Increase blood glucose levels amino acids = used in gluconeogenesis Cortex made up of 3 histological zones: Stimulate hydrolysis of stored triglycerides ( FFA DNA synthesis: inhibits DNA synthesis (don’t 1. Zona Glomerulosa : mineralocorticoids (Aldosterone) = affect for energy) want to waste energy on growing) sodium & potassium metabolism Increase cardiac output Inhibits inflammation: cortisol inhibits 1st step in 2. Zona fasciculata : glucocortoids = regulate blood glucose pathway of inflammation ( inhibits aracadonic during period of stress. Affects protein, carb & lipid acid release) During stress metabolism 3. Zona reticularis : sex hormones, same effect as testosterone & Canine Cushings : hyperadrenocorticism Stress = response to factors that threaten to alter bodies but less potent internal environment too much cortisol Regulation: Pituitary dependent Stress cause activation of sympathetic nervous system: tumour of pituitary gland = chronic high ACTH Catecholamines = released from adrenal medulla —> Glucocorticoid regulation levels - high cortisol levels - negative feedback short term stress hypothalamus releases : ACTH-RH doesn’t work Glucocorticoids = released from adrenal cortex —> Stimulates anterior pituitary to release ACTH Iantrogenic cushings ~ long term stress Adrenal cortex releases glucocorticoids and Androgens prolonged use of corticosteroid medication Regulated by: negative feedback loop (inhibits hypothalamus & Drugs provide negative feedback - ACTH levels anterior pituitary) Addisons disease - hypoadrenocorticism low - adrenal gland doesn’t make own cortisol - adrenal gland atrophy Mineralocorticoids regulated by Too little cortisol RAAS autoimmune destruction of the adrenal gland Symptoms : alopecia, thin skin, comadones, immune Extracellular concentration of potassium Clinical signs: poor appetite, weakness, suppression, pot bellied appearance dehydration, vomiting Endocrine part Rennin Erythropoietin Calcitriol Regulates blood glucose levels released in response to decreased blood released in response to lower active form of Vit D insulin —> decrease blood glucose, production of pressure oxygen carrying capacity of Produced in response to glycogen increases Activates angiotensin 11, aldosterone & blood PTH, increases Glucagon —> increases blood glucose levels, ADH Induces production of absorption of calcium gluconeogenesis stimulated Water & sodium retention erythrocytes in bone marrow from GIT Increase blood pressure Insulin · Stimulation of secretion increases blood glucose levels Diabetes mellitus Parasympathetic nerve stimulation glucose uptake into cell impaired Inhibition of secretion Hyperglycaemia: adrenalin results : glucosuria & osmotic diuretics Increased sympathetic nerve stimulation ( dilutes urine + tons of it) PU/PD —> urinate often, drink a lot of Extra level of regulation: fluid 1. GLP = glucagon-like polypeptide Polyphagia with weight loss 2. GIP = gastric inhibitory peptide Type 1 : insulin dependent Effects: dogs overall anabolic —> promotes the incorporation of Glucagon Pancreatic cells not producing insulin - glucose, amino acids & fatty acids into cellular autoimmune problem stores thus decreasing levels in blood Opposite effect of insulin Needs exogenous insulin (insulin Glucose uptake & glycogen synthesis stimulated by decrease blood glucose concentrations injections) Amino acid uptake & protein synthesis In adipose tissue = increased formation of glycerol & Sympathetic nervous system —> insulin stopped & glucagon stored Type 2: insulin independent free fatty acids needed to make triglycerides cats Inhibits hormone sensitive lipase (enzyme that breaks Overall effect: Decreased sensitivity of target cells to down triglycerides) increase blood glucose by 3 mechanisms : glycogenolysis, insulin gluconeogenesis & breakdown of triglycerides to release Associated with obesity Exceptions : nerve cells - glucose uptake is independent of FFA Can be solved by a lifestyle change insulin  Stimulates by growth hormone (GH) from pituitary gland secretes growth factors (insulin-like growth factor) Mediate growth in young animals Stimulated by increased blood pressure Stimulates by FSH & LH from: · Atrial natriuretic peptide · Ovaries induces excretion of sodium in kidney estrogen : development of follicle Opposite effect to aldosterone Progesterone: maintain pregnancy Blood pressure drops · Testis testosterone: produce sperm, growth of muscles & skeleton Produces vitamin D when exposed to sunlight hydroxylated in liver stored in kidney Vit d is activated in kidney in response to PTH = improves calcium absorption from the GIT Fat cells GIT Secrete leptin the larger the fat stores the higher the plasma levels of Gastrin = secretion of hydrochloric acid leptin (measured in hypothalamus) Secretin = secretion of bicarbonate in pancreas Gives brain information about size of fat stores Cholecystokinin (CCK) = secretion of pancreatic enzymes & contraction of gallbladder Functions: 1. Regulates appetite (high leptin levels, decreases appetite) Regulate the digestive process 2. Plays a role in fertility (decreased fertility of thin animals) Deficiency of leptin receptors = can cause obesity  Immunology Functions I protect the body against disease causing invaders Removal of injured or dead cells Disease causing invaders (Microbes) Attack & remove cancer cells Consists of specialised cells & large amount of proteins 1. Pathogenic - will cause disease if they present in all tissue - immune response happens become established in the body quickly 2. Commensals - live in symbiosis with the body (beneficial) Allergies = inappropriate or over reaction of the immune system Pathogenic microbes have strategies to establish themselves in the body. Mechanisms for pathogen entry: The immune system some invade through skin, mucous Two branches : synergistic membranes or respiratory tract Others require physical damage to the skin The innate system: non-specific inborn to gain entry Rapid response = bc already there Others use biting insects (vectors) to gain Lacks specificity = acts against any pathogen access —> tick bite fever, fleas vector for No memory worm eggs The adaptive immune system: specific develops after birth Slower response for first infection - Very specific Viruses Bacteria Memory cells: 1st time animal infected = slow response when learning to recognise an invader. 2nd time the Not a cell : consist of protein coat animal is infected = a very rapid response to the return Are cells & nuclei acid —> no cell of the recognised pathogen (immunity) reproduced of host cells membrane or cytosol, cannot Depends on type of antigens you’ve been presented WBC phagocytose replicate on its own with bacteria lack enzymes for metabolism, growth & reproduction How they reproduce: need to invade host cell DNA to replicate Cut open host cell DNA and inserts itself in there  External component Innate immune system I Mechanical barrier to infection: Internal component 5 different types of 1. The skin = makes it difficult for bacteria to establish a colony bc: macrophages: constantly shedding cells Cellular defense: Is oily & slightly acidic = pH doesn’t handle acid well neutrophils microglial cells in Commensal bacteria compete with pathogens —> they outcompete pathogens, Macrophages CNS they have a faster multiplying rate than pathogens —> over washing skin, Lymphocytes - natural killer cells Macrophages in damages commensal barrier making it easier for pathogens to enter connective tissue 2. The mucous membranes Cells form part of the innate immune system bc they can pick up on Kupffer cells in liver mucus & mucociliary clearance system : respiratory epithelium & mucocilliary nonspecific markers that allow them to target pathogens/ cancer Alveolar mechanism + coughing. GIT —> HCl, saliva also thick layer of epithelium cells cells macrophages Only a single layer of epithelial cells - most vulnerable Osteoclasts in bone Non cellular factors tissue complement system Cytokines Neutrophils vs macrophages Lactoferrin How are they able to phagocytose? (Properties) Neutrophils Amoeboid movement/diapedesis deplete quickly Phagocytic cells can change shape (well developed cytoskeleton) Smaller than macrophages Allows them to squeeze through pores Very rapid response Types: (fenestrations) into infected tissue Can only phagocytose 5-25 1. Neutrophils bacteria 2. Macrophages Chemotaxis release cytokines that release more chemotaxis Macrophages (mature monocytes) How innate & adaptive system compliment each other: Chemical substances produced by bacteria &/ larger all bacteria have markers on their cell membranes that allow the innate destroyed tissue attract phagocytes to the area Slower response immune system to recognise & destroy them Allows the concentration of these cells to be Can phagocytose hundreds of The adaptive immune system helps to improve this identification process low in the blood yet high at the air of infection bacteria before they die (opsonization) —> antibodies also have the ability to tell cell if foreign Tidy up dead neutrophils & bodies are there) Phagocytosis damaged cells  Complement system (Globulins) Cytokines e ! Natural killer cells * t still part of cellular defence Globulins = proteins made by liver, circulate in circulatory system as Released at site of infection by precursors macrophages, neutrophils & NKC Type of lymphocyte circulate constantly as inactive precursors These chemical signalling molecules function: destroy virus infected or cancer infected cells Activated in response to an infection —> can be activated by help to regulate the immune response by destroying their cell membranes by inserting antibodies & by non specific routes (useful in early stage of communication between perforins —> perforated cell membrane, like bombs infection) leukocytes & body cells that shoot holes in it, cell leaks & cells can’t function Induce fever What the complement system does : Induce pain - act as noxious Why is it part of the innate immune system? destroys microorganisms by attacking their surface membrane stimuli (stimulate pain pathways) Because Natural killer cells recognise non-specific Enhances capillary permeability Recruit neutrophils & receptors that indicate the body cell is in trouble Acts as chemotaxin monocytes —> recruits Stimulates phagocytosis by acting as an opsonin chemotaxis which is NB bc it amplifies inflammation process Innate immune system Inflammation Steps in inflammatory reaction Lactoferrin Def: Local reaction to infection or injury Step 1 macrophages in skin = first line of defence —> stationary & few in numbe