Endocrine System - Week 10 Lecture Notes PDF

**[Week 10]** **[Dr Pierce lecture 1 Endocrine system]** **Endocrine vs nervous system** - The autonomic nervous and endocrine system maintain homeostasis **Endocrine system development** - Glands that produce steroid hormones (gonads, adrenal cortex) 1. Mesoderm - Glands that produce...

**[Week 10]** **[Dr Pierce lecture 1 Endocrine system]** **Endocrine vs nervous system** - The autonomic nervous and endocrine system maintain homeostasis **Endocrine system development** - Glands that produce steroid hormones (gonads, adrenal cortex) 1. Mesoderm - Glands that produce amine, peptide and protein hormones 1. Ectoderm- pituitary and pineal gland, adrenal medulla (neuroectoderm) 2. Endoderm- thyroid and parathyroid glands, pancreas and thymus **Endocrine glands** - Ductless glands- primary function is to secrete hormones directly into surrounding fluid - The same in males and females except testes and ovaries - Some glands with both endocrine and exocrine function e.g. pancreas - Liver- releases hormones, bile into ducts and non-hormonal products (albumin) and blood clotting factors) into blood - Other tissues, e.g. adipose tissue, also have endocrine functions **Chemical and neural endocrine gland stimuli**  **Classes of hormones (based of chemical structure)** 1. Amine hormones - Synthesised from a single amino acid (tryptophan or tyrosine) - E.g. melatonin, adrenaline, noradrenaline and dopamine 2. Peptide and protein hormones - Peptide hormones- multiple amino acids that link to form a short amino acid change e.g. growth hormone - Protein hormones- longer polypeptides e.g. insulin 3. Lipid-derived steroid hormones - Mostly derived from cholesterol - E.g. oestrogen and testosterone i. Both amine and peptide and protein hormones are water-soluble and insoluble in lipids- cannot pass through cell membranes ii. Lipid- soluble and non-polar-can diffuse across cell membranes **Intracellular hormone receptors** - Lipid-derived hormones readily diffuse through cell membrane and bind to receptors in cytosol - Thyroid hormones contain benzene rings studded with iodine-also lipid-soluble and can enter the cell - Receptor-hormone complex enters nucleus and binds to target gene on DNA - Gene transcription creates mRNA-translated into desired protein **Cell membrane hormone receptors** - Hydrophilic hormones unable to diffuse through lipid bilayer - All amino acid-derived hormones except thyroid hormones - Do not directly affect transcription of target genes but initiate signalling cascade via a second messenger - Hormone is first messenger and cAMP most used second messenger **Hypothalamus-pituitary axis** - Command centre of the endocrine system - Hypothalamus 1. Structure of diencephalon located anterior and inferior to thalamus 2. Both neural and endocrine functions 3. Anatomically and functionally related to pituitary gland (or hypophysis) - Pituitary gland (hypophysis) 1. 2- lobed organ suspended from hypothalamus by the infundibulum (pituitary stalk) - Posterior pituitary (neurohypophysis)- neural tissue derived from hypothalamic tissue - Anterior pituitary- (adenohypophysis)- glandular tissue developed from the primitive digestive tract **Hypothalamic hormones**  **Anterior pituitary** - Hypothalamic hormones secreted by neurons but enter AP through hypophyseal portal system 1. Can stimulate or inhibit AP hormone secretion - 7 AP hormones: follicle-stimulating hormone (FSH), luteinising hormone (LH), Adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), prolactin (PRL), beta-endorphin, and growth hormone (GH)- FLAT PEG - FSH, LH, ACTH and TSH (FLAT) referred to as tropic hormones- turn on or off other endocrine glands **Gonadotropins (FSH and LH)** - Regulate function of ovaries and testes - Release triggered by GnRH during and after puberty - FSH 1. Stimulates production and maturation of gametes, including ova in women and sperm (Sertoli cells) in men 2. Also promotes follicular growth- release of oestrogen in ovaries - LH 1. Triggers ovulation and production of oestrogens and progesterone by ovaries 2. Stimulates production of testosterone in Leydig cells of testes **Prolactin** - In females, stimulates breast development and milk production (lactation) - Normally inhibited by prolactin-inhibiting factor (PIF; dopamine) - Levels rise during pregnancy in response to prolactin-releasing factors (e.g. oxytocin and TRH) from hypothalamus - Suckling most powerful stimulus for PRL release - No negative feedback system- without inhibition by dopamine, prolactin would be secreted indefinitely **Growth Hormone (somatropin)** - GH levels controlled by release of GHRH and GHIH (somatostatin) - Primary function is anabolic- mediates growth and protein synthesis by triggering the liver and other tissues to produce insulin-like growth factors (IGFs) - IGFs enhance cellular proliferation and inhibit apoptosis-stimulate cells to increase amino acid uptake from blood for protein synthesis, particularly skeletal muscle and cartilage cells - Also promotes lipolysis and inhibits glucose uptake **Adrenal glands** **Adrenocorticotropic hormone (corticotropin)** - ACTH release triggered by corticotropin-releasing hormone (DRH)-naturally occurring occurs in a daily rhythm - Internal and external factors such as fever, hypoglycemia and stressors can also trigger the release of CRH, and hence ACTH - Stimulates adrenal cortex to synthesise and release corticosteroid hormones- cortisol, aldosterone and androgens **Adrenal gland hormones- overview** - Wedges of glandular and neuroendocrine tissue adhering to top of kidneys by a fibrous capsule - Rich blood and nerve supply **Adrenal cortex** - Component of hypothalamic-pituitary-adrenal axis (HPA) - CRH stimulates ACTH release - ACTH stimulates adrenal cortex to produce mineralocorticoids, glucocorticoids and androgens- important for regulation of long-term stress response, blood pressure and blood volume, nutrient uptake and storage, fluid and electrolyte balance and inflammation **Zona glomerulosa- Mineralocorticoids** - Aldosterone- major mineralocorticoid - Affect body minerals, especially Na+ and K+- essential for fluid and electrolyte balance - Important in regulating Na+ and K+ ion concentrations in urine, sweat and saliva - For example, in response to low blood Na+, blood pressure or blood volume, aldosterone increases Na+ retention, blood volume and blood pressure **Zona fasciculata- Glucocorticoids** - Major role in glucose metabolism- cortisol most important - Inhibits tissue building while stimulating breakdown of stored nutrients to maintain adequate fuel supplies- increases blood sugar - Long-term cortisol- promotes catabolism of glycogen to glucose, stored triglyceride into fatty acids and glycerol, and muscle proteins into amino acids to synthesise additional glucose and ketones for fuel - Downregulates inflammatory mediators that are important in innate immunity - Medications containing glucocorticoids-inhibit the inflammatory response **Zona reticularis- Androgens** - Small amounts of androgens produced in zona reticularis - Converted to testosterone or oestrogens in tissues - May contribute to sex drive in adult women but function in adult men not well understood - Become main source of oestrogen in post-menopausal women as ovarian functions decline **Adrenal medulla** - Modified sympathetic ganglion- an extension of the autonomic nervous system and part of sympathoadrenal system - Secretes adrenaline and noradrenaline (4 to 1 ratio) into systemic circulation in response to acute, short-term danger or stress-controlled by a neural pathway from hypothalamus - Fight-or-flight response: increased blood glucose, heart rate, pulse and blood pressure; dilation of airways and vasodilation of lungs, brain, heart and skeletal muscle but vasoconstriction in liver, kidneys, GI tract and skin - Other effects: dry mouth, loss of appetite, pupil dilation and loss of peripheral vision **Acute vs chronic stress response**  **Thyroid and parathyroid glands** **Thyroid-stimulating hormone (thyrotropin. TSH)** - Released in response to TRH - Stimulates normal development and secretory activity of thyroid gland - Triggers secretion of thyroid hormones by thyroid follicle cells- triiodothyronine (T3) and thyroxine (T4) - Elevated levels of T3 and T4 in blood trigger a drop in production of TRH and subsequently, TSH **Thyroid hormones** - Thyroid hormones produced in colloid-containing follicles when mineral iodine atoms attach to the glycoprotein thyroglobulin- diffuse across the follicle cell membrane and enter the bloodstream - Triiodothyronine (T3) with three iodine and thyroxine (T4) with four iodine atoms - T4 converted into the more active T3 with a shorter half-life **T3 and T4 are metabolic hormones** - Influence basal metabolic rate 1. Increased nutrient breakdown and use of oxygen to produce ATP 2. Increased glucose oxidation with high level of heat as byproduct - Essential for foetal and childhood tissue development and growth, especially nervous system - Complex interrelationship with reproductive hormones- deficiencies can influence libido, fertility and other aspects of reproductive function - Increase body's sensitivity to adrenaline and noradrenaline by upregulation of receptors in blood vessels- excessive T3 and T4 accelerate heart rate, strengthen heartbeat, and raise blood pressure **Calcitonin** - Produced by parafollicular cells in tissue between thyroid follicles - Released in response to a rise in blood calcium levels- appears to decrease blood calcium concentrations by: 1. Inhibiting osteoclast activity 2. Increasing osteoblast activity 3. Decreasing calcium absorption in intestines 4. Increasing calcium loss in the urine - Functions usually not significant in maintaining calcium homeostasis- importance of calcitonin is not entirely understood **Parathyroid glands** - Embedded in the posterior surface of the thyroid gland - Chief cells produce and secrete parathyroid hormone (PTH) in response to low blood calcium levels - PTH 1. Exerts direct effects on bone and kidney and indirect effects on intestine through calcitriol (metabolite of vitamin D3 produced in kidneys) - PTH + calcitriol 1. Stimulate osteoclastic bone resorption and inhibit osteoblasts 2. Increase intestinal calcium and renal calcium reabsorption 3. Negative feedback loop- rising blood calcium levels inhibit further release of PTH **Posterior pituitary** - Extension of hypothalamic neurons - Cell bodies rest in hypothalamus, but axons descend as hypothalamic- hypophyseal tract to posterior pituitary - Does not produce hormones but stores and secretes hormones produced by hypothalamus - Oxytocin from paraventricular nuclei and ADH from supraoptic into blood **ADH (vasopressin)** - Released in response to increase in plasma osmolarity (i.e. water loss or reduced intake) - Promotes water reabsorption from forming urine in kidneys- conserves water - Can also cause vasoconstriction (hence vasopressin) and raise blood pressure in high concentrations - Negative feedback loop- as blood osmolarity decreases, hypothalamic osmoreceptors prompt decreased ADH secretion - Drugs, e.g. alcohol, can affect ADH secretion **Oxytocin** - Stimulates uterine contractions and dilation of the cervix - Continually released throughout childbirth through as positive feedback mechanism - Continues to play a role in maternal and newborn health- necessary for milk ejection reflex (let down) and contributes to parent-newborn bonding (attachment) - Also thought to be involved in feelings of love and closeness as well as sexual response **[Dr Pierce L2- Endocrine system Wrap-up]** **Sympathetic Nervous system** - Accelerates Heart rate - Constricts blood vessels - Raises blood pressure - And other generally stimulating functions **Parasympathetic nervous system** - Slows heart rate - Increases intestinal and gland activity - And other inhibitory or calming functions **Endocrine pancreas** - Pancreatic islets (previously islets of Langerhans) secrete glucagon, insulin, somatostatin and pancreatic polypeptide - Alpha cells- release glucagon in response to low blood glucose - Beta cells- release insulin in response to high blood glucose - Delta cells- release somatostatin which inhibits glucagon and insulin release - PP cells- release PP which plays a role in appetite and regulation of pancreatic secretions **Regulation of blood glucose- Insulin** - Release triggered by gastrointestinal tract hormones in the presence of food and further stimulated by rising blood glucose levels - Primary targets are skeletal muscle and adipose tissue cells- require insulin for glucose uptake - No insulin receptors on red blood cells and cells of brain, liver, kidneys, and lining of the small intestine- do not require insulin for glucose uptake - Appears to trigger multiple biochemical reactions that result in rapid movement of glucose transporter vesicles to cell membrane, where they facilitate glucose into cell **Processes moderated by insulin** - Facilitates uptake of glucose from the blood and stimulates glycolysis, lowering blood glucose levels - Stimulates glycogenesis in liver and skeletal muscle and inhibits glycogenolysis and glucogenesis - Also promotes triglyceride and protein synthesis - Gluconeogenesis- the process of making glucose from its own breakdown products or from the breakdown products of lipids or proteins - Glycogenolysis- liver converts its stores of glycogen back into glucose and release glucose into blood - Glycogenesis- the process of glycogen synthesis, in which glucose molecules are added to chains of glycogen for storage; opposite of glycogenolysis - Glycolysis- the metabolic pathway that converts glucose into pyruvate in the cytosol **Glucagon** - Release triggered by falling blood glucose levels sensed by receptors in pancreas - Stimulates gluconeogenesis, glycogenolysis, and the release of glucose into the circulation, raising blood glucose levels **Pineal gland** - Function not entirely clear - Pinealocytes produce and secrete the amine hormone melatonin (derived from serotonin) - Melatonin secretion dependent on light level - Daylight: production is inhibited-low blood melatonin levels promote wakefulness - Declining light levels: production increases, boosting blood levels and causing drowsiness **Organs with endocrine function** **Kidneys** - Play a role in regulating blood calcium levels via calcitriol production from vitamin D3, released in response to PTH secretion (PTH) - Produce erythropoietin (EPO) in response to low oxygen levels- stimulates production of red blood cells in bone marrow, thereby increasing oxygen delivery to tissues **Adipose tissue** - Leptin- produces feeling of satiety after a meal, thereby reducing appetite- also appears to trigger increasing deposition of cortical bone - Adiponectin- appears to reduce insulin resistance and protect blood vessels from inflammation and atherosclerosis- lower in obese people and rise following weight loss **[Dr Miller L1- The liver and its metabolic function]** **Liver functions** - Metabolism of: 1. Carbohydrates, proteins and fats 2. Steroid hormones 3. Drugs - Regulation of glucose levels (glycogenesis/glycogenolysis, gluconeogenesis) - Synthesis of: 1. Bilirubin 2. Most plasma proteins e.g. Albumin, clotting factors 3. Urea from ammonia - Formation and secretion of bile - Storage of vitamins and iron **Anatomy of the liver** - Located in upper right of abdominal cavity - 2% of body weight - Regeneration- can lose up to 80% - Blood supply 1. Hepatic artery (300mL/min) 2. Hepatic portal vein (1000mL/min) **Anatomy of liver** - Functional unit is lobule- 50,000-100,000 in liver - Vessels in: 1. Hepatic portal vein 2. Hepatic artery - Vessels out: 1. Central vein- hepatic vein- vena cava 2. Bile canaliculi 3. Lymphatics **Cells of the liver** - Hepatocytes 1. Synthesis proteins 2. Produce bile 3. Process nutrients 4. Store fat-soluble vitamins 5. Detoxification (drugs, ammonia) - Endothelial cells 1. Line sinusoids 2. Porous - Kupffer cells 1. Resident macrophages **Role of liver in digestion** - Digestion completed in small intestine - Nutrients absorbed into blood stream - More to liver for processing **Metabolism**- sum of all chemical processes involved in maintaining the dynamic state of the cell **Metabolism of carbohydrates** - The liver helps control blood glucose levels 1. Convert glucose to glycogen 2. Convert glycogen to glucose 3. Performs gluconeogenesis 4. Converts galactose and fructose to glucose **Metabolism of fats** - Breakdown of triglycerides to fatty acids and glycerol - Glycerol- glucose - Fatty acids- acetyl CoA - Acetyl CoA- Acetoacetic acid- other tissues - Synthesis of cholesterol 1. Plasma membrane, lipid rafts, bile salts, steroid hormones - Synthesis of phospholipids 1. Plasma membrane - Excess proteins, CHOs-Fat 1. Adipose tissue **Metabolism of proteins** - Deamination of amino acids - Produces ammonia 1. Toxic 2. Hepatic coma 3. Deamination and bacterial sources - Conversion of ammonia to urea for excretion **Protein synthesis** - All plasma proteins except antibodies - 50g/day - Albumin maintains normal fluid balance between the bloodstream and the tissues - Synthesis of non-essential amino acids - Break in blood vessel triggers coagulation cascade - Liver synthesises important clotting factors - Fibrinogen, prothrombin, activating factors - Vitamin K required for many of these **Iron and vitamin storage** - Produces apoferritin 1. Combines with iron to produce ferritin - Stores vitamins e.g. A, D and B12 1. Normal vision and immune function 2. Calcium regulation 3. DNA synthesis **Bile** - Hepatocytes secrete into canaliculi- bile duct- gall bladder - Fluid containing water, electrolytes, bile acids, cholesterol, phospholipids - Bile acids 1. Amphipathic 2. Emulsification of fats for absorption 3. Absorption of fat-soluble vitamins (Vitamins A, D, E and K) - Excretion of cholesterol and bilirubin **Excretion of bilirubin** - Breakdown product of Hb - Lipid-soluble - Conjugating in liver, released into intestine in bile - Excreted in faeces - Buildup is sign of liver disease **Drug and hormone inactivation and excretion** - Main site for metabolism leading to excretion - Drugs 1. Phase 1, and phase 11 reactions - Hormones 1. Inactivation to regulate levels 2. Short half-life **Relevance to dentistry** - Oral signs of liver disease include 1. Jaundice, bleeding disorders, smooth tongue, xerostomia, bruxism, cheilitis, perioral rash - Implications of liver disease 1. Can have excessive bleeding with oral surgery 2. Reduced metabolism of drugs **Liver disease** - Common problem - Due to loss of hepatocyte function or impaired blood flow - Main causes are: 1. Infectious diseases- viruses, parasites, aspergillus 2. Alcohol abuse 3. Metabolic disorders 4. Liver cancer **Infectious diseases** - Viruses- Hepatitis A, B, C, D, E - Some parasites 1. Flukes, protozoans - Damage is from infectious process or immune response **Alcohol-induced liver disease** - Metabolism of alcohol produces acetaldehyde 1. Affects mitochondria 2. Increased lipid and ketone synthesis - Fatty liver disease - Alcoholic hepatitis - Cirrhosis **Cirrhosis** - Irreversible end-stage of liver injury 1. Fibrosis and scar tissue 2. Block blood flow i. Less protein synthesis ii. Reduced metabolism of drugs - Biliary cirrhosis 1. Gallstones obstruct bile flow 2. Formed from abnormal composition of bile, stasis of bile - Can cause jaundice **Metabolic disorders** - Metabolic syndrome 1. Type 2 diabetes 2. Insulin resistance 3. Non-alcoholic fatty liver disease - Some genetic disorders 1. Wilson's disease (copper), hereditary hemochromatosis (iron) **Liver cancer** - Hepatocellular or cholangiocarcinoma - Associated with cirrhosis - Risk factors 1. Hepatitis B or C, opisthorchis 2. Fatty liver disease 3. Genetic disorders 4. Obesity, smoking, alcohol consumption **Hepatocellular failure** - Leads to a number of problems 1. Jaundice 2. Glucose imbalance 3. Muscle wasting 4. Hypoalbuminemia 5. Bleeding disorders 6. Osteomalacia 7. Feminisation **Impaired blood flow** - Increased resistance due to fibrosis and degeneration of liver tissue - Increases pressure in the portal circulation - Decreases drainage from GI tract - Varices and ascites **[Dr Miller L2- Hepatic disorders]** **Importance of liver disorders** - Normal liver function has little impact on dentistry - Liver disorders can impact dental procedures 1. Increased risk of bleeding during oral surgery 2. Increased risk of toxicity with drugs - Disorders due to infectious disease, alcohol abuse or metabolic disorders - Damage is due to hepatocellular failure or impaired blood flow **Hepatitis** - Inflammation of liver tissue - Can be caused by viruses or other infectious microorganisms 1. Hepatitis, A, B and C of most concern 2. Acute infections often self-limiting 3. Chronic- lasts for more than 6 months - Autoimmune hepatitis - Principle cause of liver disease, cirrhosis and liver cancer - Few treatments - Transplant needed in end-stage disease **Hepatitis B** - Highly prevalent enveloped DNA virus - Spread by exposure to infected bodily fluids 1. Sexual transmission, mother-to-baby, contact with infected blood or saliva, needle-stick injury - Symptoms are jaundice, dark urine, fatigue, nausea, abdominal pain - Damage from infectious process or immune response - Acute or chronic - Chronic infection can lead to cirrhosis or liver cancer - Prevented by vaccination **Hepatitis C** - RNA virus - Transmitted by contact with infected blood 1. Some sexual transmission; vertical transmission in HIV+ mothers - Symptoms include nausea, vomiting, jaundice, abdominal pain, anxiety, depression - Antiviral medications provide cure 1. Target viral replication - No vaccine so patients with chronic HCV should have HBV and HAV vaccines **Hepatitis A and E** - Spread by faecal-oral route - Contaminated food or water - Both are normally self-limiting - Asymptomatic in children, adults have fever, malaise, jaundice - Avoid alcohol, paracetamol, any hepatotoxin - Hepatitis A vaccine available for high-risk groups **Parasitic infections** - Malaria 1. Liver stage - Flukes 1. Schistosoma 2. Opisthorchis - Common in tropical areas **Drug induced liver disease** - Liver is main site of drug metabolism - Exposed to high levels of drug metabolites - Common side effect in hepatotoxicity 1. Higher doses **Drug metabolism** - Many therapeutic drugs and natural herbal remedies can cause liver damage 1. Lipid peroxidation, generation of free radicals, glutathione depletion, alteration of sulfhydryl groups - Patients not always aware of what they are taking - Paracetamol is present in a number of different medications - E.g. Panadol, cold and flu, decongestants - Hepatotoxicity from toxic doses of paracetamol causes 8000 hospitalisations per year and 170 deaths 1. 4g/day (8x500mg tablets)  **Signs of disease** - Jaundice is most characteristic sign of liver disease 1. Build up of bilirubin in tissues - Formed as a breakdown product of haemoglobin - Transported to liver by albumin - Hepatocytes conjugate it and excrete it in bile - Problems at any point result in build up **[Dr Simcock L1- Gastrointestinal physiology 1, secretions of the gastrointestinal tract and their regulation]** **The mouth** **Salivation** - Parotid 1. Serous (hydrate) - Sublingual 1. Mucus (lubricate) - Submandibular 1. Serous (hydrate) **The mouth** - Lubrication/hydration of food - Digestive enzymes 1. Lingual lipase- digestion of triglycerides 2. Lingual (salivary) amylase- Digestion of polysaccharides (starch) 3. Lysozyme- Digestion of bacteria **Gastric digestion** - gastric glands secrete 1. acid 2. pepsinogen 3. lipase 4. mucus **The small intestine- acid neutralisation** **Digestion phase- the duodenum** - Relatively steady flow from stomach **Neutralise the chyme** - Release bicarbonate **Pancreatic secretions** - Release bicarbonate - Release digestive enzymes **Gall bladder secretion** - Bile (lipid emulsification) - Bicarbonate **Motility- the mouth** **Swallowing (deglutition)** - Epiglottis closes- prevents food going into lungs - Bolus pushed back- by pushing tongue to top of palate - Oropharynx relaxes- allows food to pass into the larynx, into oesophagus - Peristalsis **The oesophagus** - Propel food to the stomach - Upper third skeletal muscle - Lower two thirds smooth muscle - Circular and longitudinal muscle contract - Peristaltic waves - bidirectional - Peristalsis- involuntary muscle movement happening in the digestive system **Primary peristalsis** - Starts at pharynx - Involves skeletal muscle 1. Regulated by vagus - Circular muscle 1. Relaxes then contracts - Longitudinal muscle contracts **Secondary peristalsis** - Muscle starts relaxed - Bolus of digesta causes stretch - Stretch causes contraction - Can be reversed **The stomach** - Muscular contractions and mixing - Cardiac sphincter (lower oesophageal sphincter) 1. Seals from the oesophagus - Pyloric sphincter 1. Seals from duodenum **Motility in the stomach** - LOS should remain shut - Pylorus regulates flow - Churning- peristalsis, but pylorus shut - Emptying- peristalsis, but pylorus open **Digestion prior to the intestine** - Carbohydrate- polysaccharides digested by amylase (mouth) - Proteins- digested by acid peptides by pepsin (stomach) - Lipids- triglycerides digested by lingual and gastric lipase - Periodic relaxation of the pyloric sphincter in stomach leads to a slow, constant flow of materials to the intestine after a large meal. **Intestinal epithelial cells** - Organised into crypts and villi - Cells growth from crypts, extend to villi - Cell membrane have microvilli - Increase surface area - One cell thick **The small intestine- digestion** **Digestion duodenum** - Proteins 1. Trypsin 2. Chymotrypsin 3. Elastase 4. Carboxypeptidases 5. Aminopeptidases - Aminopeptidase on brush border of enterocytes, others from pancreas - Pancreatic released as zymogen (released in inactive form) **Digestion phase duodenum-release enzymes** - Carbohydrates- make monosaccharides 1. Amylase-pancreatic 2. Dextrinase 3. Glucolyase 4. Lactase 5. Maltase 6. Isomaltase 7. Sucrase **Digestion phase- duodenum release enzymes and bile** - **Lipids** 1. Lipase 2. Bile salts 3. Bile acids 4. Droplet formation - Pancreatic lipase works with bile to break big fat droplets down **Absorption-proteins** - Duodenum and jejunum - Di and tri peptides - Amino acids - Active transporters apical - Passive transporters basolateral **Absorption- carbohydrates** - Duodenum-jejunum - Monosaccharides - Active transport apical - Passive transport basolateral- via GLUT 2. Not insulin sensitive **Absorption lipids** - Duodenum-jejunum and ileum - Only fatty acids can be absorbed - Lipid droplets absorbed by endocytosis - Lipids digested further packaged into chylomicrons - Lacteals transport chylomicrons- secreted into lymphatics **Absorption- water and electrolytes- sodium glucose transporter** - Jejunum-ileum - 90% of GI reabsorption - Passive (ion gradient) **Dr Simcock- GI physiology L2** **Organs of the GI tract** - Upper tract- mouth, oesophagus, stomach - Mid gut- small intestine (duodenum, jejunum, ileum) - Also: pancreas, liver and gall bladder - Hindgut: caecum (appendix) (reservoir for bacteria), colon (water absorption), rectum (storage for food before passed out) **Nervous input to the gastrointestinal system** - Parasympathetic system: stimulates (acetylcholine) - Sympathetic: inhibits (noradrenaline, adrenaline) - Primary function: digestion and absorption - Secondary function: immune function, endocrine regulation **Control of secretion- control activity of tract** - Preparation- cephalic phase (neural) - Initial digestion- gastric phase (hormonal) - Regulation and digestion- intestinal phase (hormonal) - Distention- appetite control (hormonal) 1. Suppression of ghrelin, peptide YY **Regulation of salivary secretion** - Mostly parasympathetic nervous system - Some sympathetic nervous system - Stimulated by 1. Higher brain function (cephalic phase) 2. Local receptors - Requires blood vessel dilation **Regulation of gastric secretion 1**  - Most acid is secreted in the gastric phase - Most of the secretion in the stomach happens from the hormone gastrin, therefore under hormonal control - Gastric is not responsible for the stimulation of acid secretion directly, but it stimulates the body of the stomach to release histamine and histamine stimulates acid secretion **Stopping acid secretion** 1. Suppress the effects of the acid with an antacid. Stops it being secreted with a proton pump inhibitor 2. Stop histamine release **Intestinal phase** - Has an inhibitory effect on acid and enzyme secretion from the stomach to slow down acid secretion and motility of stomach - Hormonal control relying on secretin, cholecystokinin, vasoactive intestinal peptide **Regulation of secretions the small intestine** - Hormonal and neural 1. Neural stretch related 2. Hormonal stretch and chemical composition - Gastric phase 1. Gastrin - Intestinal phase - secretin, cholecystokinin, vasoactive intestinal peptide 1. inhibit acid secretion 2. inhibit gastric emptying (reducing rate) 3. stimulate pancreatic secretions (enzymes, bicarbonate) 4. stimulate gall bladder contractions **[Dr Simcock L3- motility in the GI tract]** **Disordered peristalsis and reflux** - cardiac sphincter (LOS/LES) relaxes to allow food in - stomach relaxes - GORD/GERD- inappropriate relaxation of sphincter - Disorders peristalsis- back towards mouth - Acid/stomach contents in mouth (erodes teeth) **Regulation of gastric motility** - Volume of food 1. Increased stretch - Gastrin 1. Hormone promotes emptying - Inhibition by intestinal hormones (especially cholecystokinin) 1. Intestinal acid 2. Intestinal distension 3. Intestinal proteins and fats- hard to digest **Small intestine- mixing and motility** - Same muscle as lower oesophagus - Segmentation and peristalsis - Propulsion towards colon - Regulated by local electrical responses and hormones **Dr Simcock L4- Digestion and absorption of macronutrients and water and electrolyte** **Absorption processes** - Columnar epithelium- good metabolic function, leaky due to poor tight junctions, contain villi and microvilli, last 4 days - High turnover - Mostly absorptive - Some goblet cells **Structure of crypts and glands** - Crypts- proliferative - Glands absorptive - Capillaries- Amino acids, sugars - Lacteals- lipids **Nutrient passage from small intestine to body** - Blood passes from superior mesenteric to hepatic portal vein - Lacteals drain into thoracic duct into left innominate vein - Liver processes nutrients 1. Regulates outflow of nutrients 2. Processing/storage 3. Removes bacteria **Liver** - Hepatocytes process blood - Kupffer cells remove bacteria - Bile ducts drain to intestine **Colon** **Reabsorption of:** - Water - NaCl - Vitamins - Minerals - Volatile fatty acids **Fermentation in colon** - Escaping nutrients, indigestible carbohydrates - Indigestible proteins - Produces volatile fatty acids - Produces gas **[Dr Simcock L4- regulation of cellular nutrient sources]** **Metabolism during the day** - Metabolism varies during the day - Just after a meal 1. Absorptive state 2. Glucose is used and stored - A while after a meal 1. Post absorptive state 2. Glucose is conserved 3. Fatty acids main energy source **What determines whether tissues use glucose or fatty acids as an energy source** - How long since you last ate 1. Fed= much glucose 2. Fasting= local stores only - Body supply of glucose- 2 hours - Supply of lipids- weeks- months - As glucose is limited, only tissues which need it should use it (brain tissue) **The absorptive state (glycogenesis)** - Glucose utilised by tissues - Glycogen forms (liver, muscle) - Glucose- lipid (adipose) - Lipid storage adipose **Post absorptive state** - Tissues use lipid - Lipid mobilised (adipose) - Glycogen metabolised (liver) - Glucose produced (liver)