Alimentary system Flashcards

Question

What is QALY and DALY?

Answer 1

QALY - quality adjusted life year | DALY - disability adjusted life years

Answer 2

- Mortality and lost years - Absence from work - Morbidity - NHS prescription

Answer 3

Mucosa: - Epithelium - Lamina Propria: loose connective tissue, contains capillaries, nerve endings, lymphatic capillaries - Muscularis mucosae Submucosa: connective tissue, containing nerve plexus (including enteric nervous system) and larger vessels. Muscularis: smooth muscle (containing nerve plexus) Serosa/Adventitia: - connective tissue, outer lining keeping it suspended - epithelium

Answer 4

- Starts at C5 - Passes through the thorax, and diaphragm to connect to the stomach - Ends at T10 - Passes close to the trachea and aorta (if ruptures can be fatal) - Divided into thirds: Cervical (narrow), middle and lower - More smooth muscle as you go down

Answer 5

Conduit for food, drink and swallowed secretions from pharynx to stomach

Answer 6

- Non-keratinising - Stratified squamous - 'Wear and tear' lining (extremes of temp and textures) - Lubrication: mucus secreting glands (and also saliva)

Answer 7

- Upper and lower oesophageal sphincters - Tonically active: permanently closed unless swallowing - Due to pressure differences without the sphincters there would be a tendency of contents of the stomach to be drawn up or air to be drawn in - Initiation of swallowing cause nerve impulses to travel to the brain and back to open the sphincters, then once food passes the upper oesophageal sphincter it closes (to be able to breathe) whereas the lower remains open till the food enters the stomach - Structure: Mix of skeletal and smooth. Upper - skeletal, mid - mix, lower - smooth. - Involuntary control by swallowing centre in brain, though initiation is voluntary

Answer 8

- Circular muscle is particularly important - Peristaltic wave: Circular muscle above food contracts, and circular muscle below the food relaxes - Assisted by longitudinal muscle - Oesophagus detects presence of food and so can initiate a secondary peristaltic wave

Answer 9

- Lower oesophageal sphincter = skeletal muscle of diaphragm assisting the circular muscle of oesophagus to constrict and close it - As the lower part of the oesophagus is in the abdomen there is no pressure difference between it and the stomach so less likely to have stomach contents moving up - Pregnancy or a very large meal can lead to reflux - Epithelial transition from stratified squamous to simple columnar (stomach) at the zigzag (Z) line - Gastric folds (rugae) in the stomach for increased surface area to expand or contract as required

Answer 10

Initiation of a swallowing reflex to open both sphincter and allowing release (due to the pressure) of gas from the stomach

Answer 11

Breaks food down into smaller particles stored (due to acid and pepsin), hold food and release at a controlled steady state into duodenum, kill parasites and certain bacteria

Answer 12

- Simple columnar epithelium - Made up of the fundus and body (secreting mucus, HCl and pepsinogen), Cardia and pylori region (secreting mucus only) and the antrum (secretes gastrin) - Acid produced about 2L/day, can reach 150mM H+

Answer 13

- Epithelial cells secreting mucus with large amount of bicarbonate, found all over the stomach. Protects the lining of the stomach by neutralising acid at the surface - Chief cell - Protein-secreting (pepsinogen) epithelial cell, abundant RER and Golgi for packaging and modifying for export, masses of apical secretion granules. - Parietal cell - Many mitochondria to actively transport H+, cytoplasmic tubovesicles contain H+/K+ ATPase, internal canuliculi near apical surface. When active the tubular vesicle fuse with the membrane and project into the cannaliculi.

Answer 14

- Carbonic anhydrase converts CO2 and H2O to H+ and HCO3- - HCO3- is exchanged for Cl- which enters the cell - H+ ions are actively transported into the lumen in exchange for K+ ions - Cl- moves with H+ out of the cell - K+ is taken up into the cell (via Na+/K+ pump) and then exits into the lumen - Fusion of the tubular vesicles and the canaliculi mean increase no. of H+/K+ ATPase NET = secretion of HCL into the lumen

Answer 15

- Chief cells secrete pepsinogen which is an inactive precursor - The acidic environment created by the parietal cells causes a conformation change leading to enzymatic activity within the pepsinogen and cleavage of other pepsinogen molecules - This leads to production of pepsin (protease)

Answer 16

- Produced in the Pyloric antrum - Stimulates acid secretion - At very high pH gastrin secretion is supressed (i.e. empty stomach) - After meal protein content changes pH to 3/4 -> there is no inhibition of gastrin -> gastrin secretion -> increase in acid - (OR) Gastrin stimulates histamine release from chromaffin cells in the lamina propria -> acid production

Answer 17

1. Cephalic phase: Thought, sight, smell and taste of food causes impulses from brain through vagus nerve to stomach. Acetyl choline stimulates acid production by stimulating parietal cells or histamine release from chromaffin cells. 2. Gastric phase: When there is food in the stomach, the distension detected by stretch receptors signals brain through vagus, and in turn efferent impulses stimulate more acid production. Enteric nervous system also acts in response to stretch. Chemoreceptors detect to chemical changes and respond with gastrin secretion. 3. Intestinal phase: Mostly inhibitory. As stomach contents passes into the small intestine (particularly if pH

Answer 18

- Low pH of chyme stimulates secretion of enterogastrones from the small intestine. - Enterogastrones: gastric inhibitory peptidem cholecystokinin, secretin - Secreted into the blood and switch off acid production in the stomach

Answer 19

- Omeprazole: Proton pump inhibitor that prevents the release of H+ into the lumen - Ranitidine: Histamine receptor antagonist to prevent stimulation of acid production by acetyl choline or gastrin

Answer 20

To absorb nutrients, salt and water

Answer 21

- Approx. 6m long, 3.5 cm in diametre - Duodenum - 25cm - Jejenum - 2.5m - Ileum - 3.75m - All have same basic histology with some differences- no sudden transition between them - Mesentery: fan-shaped connective tissue which throws the small intestine into folds and supports the blood supply - External wall - longitudinal and circular muscles (motilit) - Internal mucosa - arranged into circular folds. Covered in villi (about 1mm tall) with invaginations known as crypts of Lieberkuhn

Answer 22

- Only occur in the small intestine (where most absorption takes place) - Increase surface area - Motile, have a rich blood supply and lymph drainage for absorption of digested nutrients - Have good innervation from the submucosal plexus - Have simple epithelium (1 cell thick) dominated by enterocytes (columnar absorptive cells)

Answer 23

``` Mucosa lined with simple columnar epithelium consisting of: - Primary enterocytes (absorptive cells) - Scattered goblet cells - Enteroendocrine cells Crypts of Lieberkuhn epithelium include: - Paneth cells - Stem cells ```

Answer 24

- Most abundant type in small intestine - Tall columnar cells with microvilli and a basal nucleus - Specialised for absorption and transport of substances - Short lifespan of about 1-6 days (average 30hrs) - Tight junctions between cells prevent paracellular movement and allow polarity of proteins

Answer 25

- About 0.5-1.5μm high - Make up the brush border - Several thousand per cell - Surface covered with glycocalyx, a rich carbohydrate later which protects from digestion and allows absorption. It traps a layer of water and mucous (unstirred layer) which regulated the rate of absorption from intestinal lumen

Answer 26

Increase the surface are from 0.4m^2 to around 200m^2 (500 fold)

Answer 27

- 2nd most abundant epithelial cell type - Mucous containing granules accumulate at the apical end -> goblet shape - Mucous = large glycoprotein that facilitates passage os material through the bowel - Abundance increases along the length of the bowel (as more water in absorbed it becomes harder to move)

Answer 28

(Chromaffin cells) - Columnar epithelial cells, scattered among the absorptive cells - In intestine most often found in the lower parts of the crypts - Hormone secreting, e.g. to influence gut motility

Answer 29

- Found only in bases of the crypts - Contain large acidophilic granules which contain antibacterial enzyme lysozyme (protect stem cells) and glycoproteins (protect from the enzymes) and zinc (co-factor of enzymes) - Engulf some bacteria and protozoa - May have a role in regulating intestinal flora

Answer 30

- Cell proliferation, differentiation and death are continuous processes in the gut epithelium - Enterocytes and goblet cells of the small intestine have a short life span (about 36hrs) - Continually replaced by dividing stem cells in the crypts

Answer 31

- Undifferentiated cells which remain capable of cell division to replace cells which die - Epithelial stem cells are essential in the GI tract to continually replenish the surface epithelium - Continually divide by mitosis - Migrate up to the tip of villus, replacing older cells that die by apoptosis ('escalator' of migration) - At villus tips cells become senescent and sloughed (shed) into the lumen of the intestine to be digested and reabsorbed - Differentiate into various cell types (pluripotent)

Answer 32

- Enterocytes are first line of defense against GI pathogens and may be affected directly by toxic substances in the diet - Effect of agents which interfere with cell function, metabolic rate etc will be diminished - Any lesions with be short-lived - If there's impaired production of new cells (e.g. radiation) there will be severe intestinal dysfunction

Answer 33

- Cholera enterotoxin results in prolonged opening of the chloride channels in the small intestine allowing uncontrolled secretion of water - Bodily fluid moves freely into the lumen and hence out through the intestine, leading to rapid, massive dehydration and death - Treatment is rehydration. Cholera bacteria will clear when the epithelium will be replaced

Answer 34

- Distinguished by presence of Brunner's glands: submucosal coiled tubular mucous glands secreting alkaline fluid, open into the base of the crypts - Alkaline secretion of Brunner's glands: neutralises acidic chyme from the stomach, protecting proximal small intestine, help optimise pH for the action of pancreatic digestive enzymes

Answer 35

- Characterised by the presence of numerous, large folds in the submucosa, called plicae circulares (or valves of Kerckring) - Also present in the duodenum and ileum but plicae in the jejenum tend to be taller, thinner and more frequent

Answer 36

- Shares some features with large intestine - Has a lot of Peyer's patches: large clusters of lymph nodules in the submucosa - Prime immune system against intestinal bacteria (other mechanisms = bactericidal paneth cells, rapid cell turnover) - Well positioned to prevent bacteria from colon migrating up into the small intestine

Answer 37

- Mix ingested food with digestive secretions and enzymes - Facilitate contact between contents of intestine and intestinal mucosa - Propel intestinal contents along the alimentary tract

Answer 38

- Segmentation (mixing) - Peristalsis (propelling) - Migratory motor complex (sweeps through gut, preventing accumulation of residue)

Answer 39

- Mixes contents of the lumen - Segmentation occurs by stationary contraction of circular muscles at intervals - More frequent contractions in duodenum compared to ileum to allow pancreatic enzymes and bile to mix with chyme - Although chyme moves in both directions the net effect is movement towards the colon

Answer 40

- Involves sequential contraction of adjacent rings of smooth muscle - Propels chyme towards the colon - Most waves of peristalsis travel about 10 cm (not full length) - Segmentation and peristalsis result in chyme being segmented, mixed and propelled towards the colon

Answer 41

- In fasting there's cycles of smooth muscle contraction - Each cycle there's contraction of adjacent segments of small intestine - Begin in stomach, migrate through small intestine towards colon. On reaching terminal ileum, next contraction starts in the duodenum - Prevents migration of colonic bacteria into the ileum and may 'clean' the intestine of residual food - Also occurs in fed state, but less ordered and less frequent

Answer 42

- Digestion and absorption of carbohydrates, proteins and lipids - Occurs in alkaline environment - Digestive enzymes and bile enter the duodenum from pancreatic duct and bile duct - Duodenal epithelium also produces its own enzymes - Digestion occurs both in the lumen and in contact with the membrane

Answer 43

- Passive diffusion: no carrier protiens, with the concentration gradient, no energy required - Facilitated diffusion: carrier proteins, with the concentration gradient, no energy required - Primary active transport: carrier proteins, against concentration gradient, energy required from hydrolysis of ATP - Secondary active transport: carrier proteins, against concentration gradient, energy required from electrochemical gradient

Answer 44

- Begins by salivary α-amylase, but it's destroyed by acidic pH in stomach - Most digestion occurs in the small intestine - Pancreatic α-amylase secreted into duodenum by pancreas in response to a meal. Continues digestion of starch and glycogen in small intestine. - Acts mainly in lumen, and some adsorbs to brush border. - Digestion of amylase products and simple carbohydrates occurs at the membrane (e.g. by maltase, lactase, sucrase)

Answer 45

- Cl- | - slightly alkaline pH (Brunner's glands in duodenum=alkaline secretion)

Answer 46

- Simple carbohydrates, e.g. monosaccharides - glucose and fructose, diasaccharides - sucrose and maltose. Broken down at membrane. - Complex carbohydrates, e.g. starch, cellulose, pectins. Sugars bonded together to form a chain. Broken down in lumen

Answer 47

Apical: - Absorption of glucose and galactose is by secondary active transport. Carrier protein = SGLT-1 (sodium-glucose transport protein) on apical membrane. - Absorption of fructose is by facilitated diffusion. Carrier protein = GLUT-5 on apical membrane Basal: - GLUT-2 facilitates exit at the basolateral membrane - Can absorb 10kg of simple sugars per day

Answer 48

- Begins in the stomach by pepsin, but pepsin is inactivated in the alkaline duodenum - Pancreatic proteases are secreted as precursors - Trypsin is activated by enterokinase, an enzyme located on duodenal brush border - Trypsin then activated the other proteases

Answer 49

- Brush border peptidases break down the larger peptides prior to absorption - Amino acids are absorbed by facilitated diffusion and secondary active transport - Di- and tri-peptides are absorbed using carrier proteins distinct from single amino acids - Cytoplasmic peptidases break down most of the di- and tri- peptides before they cross the basolateral membrane

Answer 50

- Lipids are poorly soluble in water - Four stage process in the small intestine: 1. Secretion of bile and lipases 2. Emulsification (bile) 3. Enzymatic hydrolysis of ester linkages 4. Solubilization of lipolytic products in bile salt micelles

Answer 51

- Fat is hydrophobic - Bile and lipases are secreted into the duodenum - Bile salts facilitate the emulsification of fat into the suspension of lipid droplets ( about 1μm diametre) - Function of emulsification is to increase the surface area for digestion - Allows pancreatic lipase to split triglycerides - A triglyceride is broken down into two free fatty acids and a monoglyceride at the fat/water interface

Answer 52

- Steroid nucleus planar with two faces (amphipathic) - Hydrophobic (nucleus and methyl) face dissolves fat - Hydrophilic (hydroxul and carboxyl) face dissolves in water - Emulsify lipids and allow diffusion of micelles into enterocytes via microvilli

Answer 53

- Micelles = hydrophilic head regions in contact with the surrounding solvent, sequestering the hydrophobic tail regions in the micelle centre - Mixed micelles in small intestine = water insoluble monoglycerides from lipolysis are solubilised by forming a lipid core, stabilised by bile salts.

Answer 54

- Lipase breaks down triglycerides into free fatty acids and monoglycerides. - Pancreatic lipase complexes with colipase - Colipase prevents bile salts from displacing lipase from the fat droplet

Answer 55

- Phopsholipase A2: hydrolyses fatty acids at the 2 position in many phospholipids, resulting in lysophospholipids and free fatty acids - Pancreatic cholesterol esterase: hydrolyses cholesterol ester to free cholesterol and fatty acid

Answer 56

- Bile salt micelles are important as they are absorbed much quicker than emulsion - Micelles allow the transport across the unstirred layer and present the fatty acids and monoglycerides to the brush border - The whole micelle is not absorbed together: bile salts are absorbed in the ileum (transported back to liver for recycling - enterohepatic circulation), but lipid absorption is completes by the middle of the jejunum

Answer 57

Monoglycerides and free fatty acids are absorbes by enterocytes and resynthesised into tri-glycerides by to pathways: - Monoglyceride acylation (major) - Phosphatidic acid pathway (minor)

Answer 58

- Fatty acids bind to the apical membrane - Fatty acid binding proteins (FABP) facilitate transfer of fatty acids from apical membrane to the smooth ER - In the smooth ER fatty acids are esterified into diglycerides and triglycerides

Answer 59

Tri-glycerides are synthesised from CoA fatty acid and α-glycerophosphate

Answer 60

- Lipoprotein particles synthesised in enterocytes as an emulsion - 80-90% triglycerides, 8-9% phospholipids, 2% cholesterol, 2% protein and a trace of carbohydrate. - Chylomicrons are transportef to the golgi and secreted across the basement membrane by exocytosis - Too big to enter blood capillaries - Enter lacteals (lymph channels) instead

Answer 61

- Ileocaecal sphincter joins the ileum of the small intestine and the caecum of the large intestine - Relaxation and contraction controls the passage of material into the colon - Also prevents the back flow of bacteria into the ileum

Answer 62

- 4 lobes: left, right, caudate and quadrate - Falciform ligament divides right (bigger) and left lobe then - The inferior free edge of the falciform ligament contains the ligamentum teres - Gall bladder is posterior in junction of segments 4 and 5 - Calot's triangle = bound by cystic duct, bile duct and cystic artery. Tringular space which is dissected in a cholecystectomy to find safe window to expose gallbladder - Superiorly: coronary ligament (right lobe), left triangular ligament - Posteriorly: Hilis (common bile duct, hepatic portal vein and hepatic portal artery), Inferior vena cava

Answer 63

Liver and biliary system have common origin with ventral part of pancreas, at the distal foregut/proximal midgut

Answer 64

- Endoderm (parencymal cells (secretory cells) originate from this): one of three germ layers in very early embryo (innermost layer). Consists of flattened cells which subsequently become columnar and the epithelial lining of multiple systems. - Mesoderm (connective tissue originates from this): middle layer. Differentiates from the rest of embryo through intracellular signally leading to polarisation by an organising centre - Somites: form skin and muscoskeletal parts of the body. - Ectoderm: outside layer

Answer 65

- Stage 11 (-29 days): Liver bud develops (hepatic diverticulum), invades septum transversum (mesoderm/connective tissue) Cell differentiation - Stage 12 (-30 days): Septum transversum (connective tissue) develops into liver stroma. Hepatic diverticulum forms hepatic trabeculae - Stage 13 (-32 days): Epithelial cord proliferation enmeshing stromal capillaries (Parenchyma entangles with connective tissue) - Stage 14 (-33 days): Enlargement of the liver bud, Haematopoietic function appears. - Stage 18 (-44 days): Bile ducts become reorganised (continuity between liver cells and gut) - Stage 18-23 (-44-56 days): Structure of the liver develops e.g. ductal plates form that receive biliary canaliculi. Begins migrating to right side. - 70 days: Liver mostly in right side

Answer 66

- 25% of resting cardiac output - Dual: 20% arterial blood from hepatic artery (left and right branches), 80% venous blood draining from gut through hepatic portal vein. - Blood from liver drains into inferior vena cava via hepatic vein - Arterial blood for oxygen supply to tissues, venous blood from gut supplies deoxygenated blood full of nutrients (for metabolic activity)

Answer 67

- 8 functionally independent segments of the liver each with their own vascular inflow, outflow and biliary drainage. - The portal vein, hepatic artery and bole duct drains centrally - The hepatic vein drains peripherally - Each segment can be resected without damaging those remaining

Answer 68

1. Caudate lobe 2. Lateral to falciform ligament and superior to portal venous supply 3. Lateral to falciform ligament and inferior to portal venous supply 4. Medial to falciform ligament 5. Medial and inferior right hemisphere 6. Posterior portion of right hemisphere 7. Above 6 8. Above 5 (medial and superior right hemisphere)

Answer 69

- Hepatocytes: 80% of cells - Endothelial cells: Lining blood vessels and sinusoids - Cholangiocytes (bile duct epithelial cells): Lining biliary structures - Kupffer cells: Fixed (liver) macrophages - Hepatic stellate cells: Vit A storage cells (Ito cells), may be activated to a fibrogenic myofibroblastic phenotype

Answer 70

- Hepatocytes: large cells with pale and rounded nuclei. Cords (sheets) radiating from the central vein. 80% of liver mass - Kupffer or Hepatic stellate cells: Flattened, dense cell nuclei that appear to be in the sinusoids

Answer 71

- Vitamin A storage | - Activation -> ECM production (fibrogenesis)

Answer 72

Fenestrated to allow lipid and other large molecule movement to and from hepatocytes

Answer 73

- Phagocytosis, including RBC breakdown | - Secretion of cytokines that promote hepatic stellate cell activation (-> proliferation, contraction and fibrogenesis)

Answer 74

- Lobules: Morphological. Classically hexagonal, divided into At the corners of the lobule (hexagon) there are portal tracts/triad (hepatic artery, vein and bile duct) - Acinis: Functional unit. Elliptical or diamond shaped, hepatocytes divided into zones dependent on proximity to arterial blood supply.

Answer 75

- Around edges of adjoining lobules | - Composed of: an arteriole, branch of the portal vein and bile duct

Answer 76

- Less clearly defined - Divided into zones, dependent on distance to vascular supply (Zone 1 = periportal, 2 = Transition zone, 3 = Pericentral) - Zone 1 (closest) receives most oxygenated blood therefore is least susceptible to ischaemic injury, but most susceptible to viral hepatitis or hemosderin deposition (iron overload)

Answer 77

- Centrilobular - Midzonal - Periportal

Answer 78

- Zone 1 is involved in gluconeogenesis, fatty acid oxidation and cholesterol synthesis - Zone 3 involved in glycolysis, lipogenesis and P450 based drug detoxification.

Answer 79

- Produced by hepatocytes - Flows along bile canaliculus to interlobular bile ducts - Into right/left hepatic ducts -> Common hepatic duct (-> Cystic duct gallbladder) -> Common bile duct -> Ampulla vater (joining of common bile duct and pancreatic duct) -> small intestine - Opposite direction to blood flow

Answer 80

- Protein metabolism: Synthesis, packaging, deamination of amino acids produce urea and reuse carbon skeleton (RER and golgi) - Carbohydrate metabolism: e.g. glycolysis, glycogenesis, glycogenolysis, glucogenesis (SER, mitochondria, cytoplasmic enzymes) - Lipid metabolism: Triglyceride metabolism - synthesis of fatty acids -> triglycerides and lipoproteins for transport to cells, and digested triglyceride chylomicron remnants processed into lipoproteins. Bile acid production (and salt e.g. Na+) (SER, peroxisomes, mitochondria) - Detoxification: Metabolise, modify/detoxifiy exogenous compounds e.g. drugs. (Lysosomes, SER)

Answer 81

- Hepatic diverticulum/bud divides in the pars hepatica and pars cystica around 4 weeks - The pars cystica develops into the gallbladder and cystic duct by around 8 weeks

Answer 82

- Gallbladder lies on ventral surface of the right lobule of the median lobe - Left and right hepatic ducts join to form the common hepatic duct - Cystic (from gallbladder) and common hepatic duct unite to form the common bile duct - Common bile duct enters the duodenum - Lower end of common bile duct is surrounded by muscle proximally known as the Sphincter of Oddi which controls release of bile

Answer 83

Large, multifunctional organ - Digestion - Biosynthesis (glucose, protein, fat, bile) - Energy metabolism - Degradation and detoxifaction

Answer 84

- After a meal, blood glucose increases and is taken up by the tissues - Stored as glycogen mainly in the muscle and liver - Breakdown of liver glycogen maintains blood glucose concentration between meals (muscle cannot release glucose back into the blood) - 24hr fast will exhaust liver glycogen (80g)

Answer 85

Gluconeogenesis: synthesis of glucose from non-carbohydrate sources - From lactate -> pyruvate --(6 ATP)--> glucose (through Cori cycle) - From amino acids via deamination (removal of amino group) e.g. Alanine -> Pyruvation -> Glucose - From triglycerides -> glycerol -> glucose

Answer 86

- Synthesises 90% of plasma proteins (remainder are γ-globulins) Makes 15-50g/day - Importance: binding/carrier function, plasma -> colloid osmotic pressure (decrease can lead to oedema) - Synthesis of blood clotting factors - Synthesis of dietary 'non-essential' amino acids by transamination

Answer 87

General: amino acid + keto acid -> new amino acid + new keto acid E.g. Alanine + α-oxoglutaric acid -> Glutamic acid + pyruvic acid

Answer 88

- Transamination - 'Non-essential' amino acids are ones which cannot be obtained from diet - Start with appropriate α-keto acid precursor - Exchange of an amino acid group from an amino acid to a keto-acid - Essential amino acids (Lys, Leu, Ile, Met, Thr, Tyr, Val, Phe) don't have appropriate keto acid precursors. - Glutamic acid is the most common intermediate in transamination reactions

Answer 89

- Deamination is the conversion of an amino acid into the corresponding keto acid by the removal of the amine group as ammonia and replacing it with a ketone - Occurs primarily of glutamic acid because it is the end product of many transamination reactions - Deaminatio = NH3 production = Highly toxic (especially to the CNS) - Liver converts NH3 to urea - Urea is a water soluble, metabolically inert, non-toxic product excreted in urine

Answer 90

- Fat is main energy store for body - 100x glycogen - Stored in adipose and liver - When glycogen store is full, liver can convert excess glucose and amino acids to fat (Lipogenesis) - Liver metabolises fat as energy store: converts fatty acids to Acetyl CoA (β-oxidation) -> TCA cycle in liver - OR Liver converts 2 Acetyl CoA -> acetoacetate (ketone body) for transport in blood, travels to other tissues --(by thiophorase)--> Acetyl CoA -> Energy Note: The liver does not have thiophorase -> cannot use ketone bodies - Ketone bodies produced in liver to be used by other tissues - Synthesises lipoproteins, cholesterol and phospholipids

Answer 91

- Chylomicrons travel in the blood from the small intestine, and are broken down to release TAGs using lipoprotein lipase - In hepatocytes TAGs, cholesterol, phospholipid and a protein coat packaged into lipoproteins which stabalises the lipid. - Synthesis of lipoproteins, cholesterol, and phospholipids allow lipid transport in aqueous medium (blood) - Allows lipid transport in aqueous medium

Answer 92

- Synthesised from Acetyl CoA connected to a sterol nucleus (also in diet) - Can be produced in different ways: - Acetyl CoA --(HMG-CoA)--> melavonate -> cholesterol - Cholesterol delivered by chylomicrons - Cholesterol delivered by HDLs from tissues - Cholesterol is then packaged in lipoproteins with phospholipids and sent around the body

Answer 93

- Active reabsorption of bile salts (and other products in bile) mainly in terminal ileum. - De-conjugation and de-hydroxylation by bacteria make bile salt lipid soluble - Absorbed by Na+/bile salt co transport -> recirculate via hepatic portal vein back to liver - Hepatocytes avidly extract bile salts (one pass clears them all) - Bile salts are re-conjugated and some re-hydroxylated before reuse - Bile salt pool is secreted twice per meal - Less than 5% of bile isn't absorbed in terminal ileum. In colon they're converted to secondary bile acids - This can prolong the action of drugs e.g morphine in liver failure

Answer 94

- Adipose tissue | - From diet in chylomicrons through lymph system

Answer 95

- VLDL: lot of triglycerides (usually what liver produces) Can be converted to: - LDL: high cholesterol phospholipid. (Bad cholesterol - atherosclerosis) Delivers to tissues - HDL: high protein content. (Good cholesterol) Removes from tissues

Answer 96

About 2-8 weeks but depends on fat stores

Answer 97

- Produced by hepatocytes then drain into canuliculi - Gall bladder holds 15-60ml - Major component = bile salts (50% dry weight) , also has cholesterol, phospholipids (lecithin), bile pigments (bilirubin, biliverdin), bicarbonate ions and water - Some components are insoluble but mostly stable

Answer 98

- Addition of carboxyl and hydroxyl of cholesterol - To form cholic acid (primary bile acids) - Conjugation with taurine or glycine - Forms bile acid conjugates (Each process increases H2O solubility) - Moves to the gall bladder, and released into duodenum when required - Bacteria in ileum de-conjugate and de-hydroxylate primary bile salts to form secondary bile salts (active form -> increases bile salts)

Answer 99

- Digestion/absorption fats: - Excretion variety substances via GI tract - Neutralise acid chyme from stomach

Answer 100

- Released into the duodenum during digestion. Small amounts during cephalic, gastric phases due to vagal nerve and gastrin - Intestinal phase, cholecystokinin (CCK) causes contraction gall bladder and relaxation of sphincter of Oddi

Answer 101

- Emulsify fat droplets with bile salts, which increases surface area for digestion - Hydrolysis of triglycerides in emulsified fat droplets into fatty acid and monoglycerides by pancreatic lipase - Dissolving fatty acids and monoglycerides into micelles to produce mixed micelles

Answer 102

- Liver breaks down/inactivates steriod and peptide hormones which are then secreted into the bile for excretion - Also performs similar role with variety of foreign compounds - usually drugs e.g. cannabis - Excretory route for excess cholesterol: lecithin allows more cholesterol in micelles. Too much cholesterol excretion = gall stones. It's also lost in salts - Excretion of bile pigments. Bilirubin from break down of haem from old red blood cells (15% from other proteins). Iron from haem group is removed in spleen and conserved. Porphyrin group reduced to bilirubin and conjugated to glucoronic acid in liver. Liver disease - gall stone made from red blood cell (dark red/black)

Answer 103

Larder function: (storage) - Vitamins (A,D,E,K) stores enough for 6-12 months, except Vit K which has a smaller store and is continuously used in blood clotting. - Iron as ferritin. Available for erythropoeisis - Vitamin B12 - Lack can lead to pernicious (megaloblastic) anaemia, nerve demyelination - Glycogen and fat store Protection: - Liver sinusoids contain tissue macraphages (Kupffer cells). Bacteria may cross from gut to blood - Kupffer cells destroy these and prevent them entering the rest of the body Ca2+ metabolism: - UV light converts cholesterol to vitamin D precursor, which requires a double hydroxylation to convert it to the active form. First is in the liver, second is in the kidneys. Lack of Vit D -> rickets

Answer 104

- Arises from the foregut at the foregut-midgut junction - Dorsal (larger, on left) and ventral buds (smaller, on right) - Ventral bud is a part of hepatobiliary bud - In development, as duodenum rotates to form C shape the ventral bud swings round to lie adjacent to the dorsal bud - Both buds fuse - Ventral bud ducts becomes main pancreatic duct, and dorsal duct can become accessory pancreatic duct

Answer 105

5 main regions - Body - Head (duct exits here) - Neck - Tail (islet tissue most abundant) - Uncinate (hook like process at bottom)

Answer 106

- Lies mainly on posterior abdominal wall extending from C-shaped duodenum to the hilum of the spleen - Main posterior relations: IVC, abdominal aorta and left kidney

Answer 107

- Coeliac artery | - Superior mesenteric artery

Answer 108

- MRI | - Angiography (especially to test for neuroendocrine tumours - blush appears)

Answer 109

- Endocrine: Secretion into blood stream to have an effect on distant target organ. From ductless glands - Exocrine: Secretion into a duct to have a direct local effect

Answer 110

- Insulin: reduced blood glucose by increasing glucose uptake, lipogenesis and glygogenesis - Glucagon: increases blood glucose by increasing gluconeogenesis and glycogenolysis - Somatostatin: 'endocrine cyanide' - inhibits other secretions

Answer 111

- Endocrine: 2% Islets of Langerhans secretes insulin and glucagon (also somatostatin and pancreatic polypeptide) which regulates blood glucose, metabolism and growth effects - Exocrine: 98% Secretes pancreatic juice into the duodenum via pancreatic duct/common bile duct which has digestive function Note: In pancreatic disease, both are affected e.g. cystic fibrosis

Answer 112

Exocrine: Ducts, acini are grape-like clusters of secretory units, acinar cells secrete pro-enzymes into ducts Endocrine: Derived from branching duct system but lose contact with ducts and become islets, differentiate into α and β-cells secreting into blood. More in tail than head of pancreas

Answer 113

- α-cells form about 15-20% of islet tissue and secrete glucagon - β-cells form about 60-70% of islet tissue and secrete insulin - δ-cells form about 5-10% of islet tissue and secrete somatostatin - Highly vascular ensuring all endocrine cells have close access to a site for secretion

Answer 114

- Low volume, viscous, enzyme-rich secreted by ACINAR CELLS | - High volume, watery, HCO3- rich secreted by DUCT and CENTRIACINAR cells

Answer 115

- Acinar cells: large, with apical secretion granules | - Duct cells: small, pale

Answer 116

- Secreted by duct and centriacinar cells - Juice is rich in bicarbonate, about 120mM (plasma - 25mM). pH 7.5-8.0 - Neutralises acid chyme from the stomach which prevents damage to duodenal mucosa and raises pH to optimum range for pancreatic enzymes to work - Washes low volume enzyme secretion out of pancreas into duodenum

Answer 117

- Duodenal pH

Answer 118

1. CO2 enters cell and carbonic anhydrase catalyses reaction with water (CO2 + H2O -> H+ + HCO3-). 2. Na+ moves down concentration gradient paracellularly (tight junctions), and H2O follows 3. Cl/HCO3- exchange at lumen allows bicarbonate secretion 4. Na+/H+ exchange at basolateral membrane into bloodstream Exchange is driven by electrochemical gradients (High ec (blood) Na, High Cl in lumen0 5. Na+ gradient into cell from blood maintained by Na/K exchange pump (uses ATP - primary transport) 6. K+ returns to blood, and Cl- to lumen via K+ and Cl- channel (CFTR)

Answer 119

- Enzymes for digestion of fat (lipases), protein (proteases) and carbohydrates (amylase) are synthesised and stored in zymogen granules - Zymogens = pro-enzymes (precursors) - Proteases are releases as inactive pro-enzymes -> protects acini and ducts from autodigestion e.g. trypsinogen - Pancreas also contains a trypsin (protease) inhibitor to prevent its activation - Enzymes only become active in the duodenum - Blockage of pancreatic duct may overload protection and result in auto-digestion (acute pancreatitis)

Answer 120

- Secreted by pancreas in inactive form trypsinogen - Duodenal mucosa secretes enzyme enterokinase (enteropeptidase) that converts trypsinogen to trypsin - Trypsin then converts all other proteolytic, and some lipolytic enzymes (Note: lipase is secreted in active form but needs colipase which is secreted as a precursor. Also lipases need bile salts for effective action)

Answer 121

- Pancreatic secretions adapt to diet e.g. high protein, low carbs, increases proportion of proteases and decreases proportion of amylases - Pancreatic enzymes (+bile) are essential for normal digestion of a meal. Lack of these can lead to malnutrition even if the dietary input is fine (unlike salivary and gastric enzymes) - Anti-obesity drug Orlistat inhibits pancreatic lipases -> inhibits intestinal fat absorption -> steatorrhea (increased faecal fat).

Answer 122

- Vagus - Cholinergic - Communicates information from the brain to gut - Originates from nucleus solitarius in brain stem

Answer 123

- Cephalic phase: Reflex response to sight/smell/taste food. Enzyme-rich component only. Low volume -> mobilises enzymes - Gastric phase: Stimulation of pancreatic secretion originating from food arriving in stomach. Same mechanisms involved as for cephalic phase - Intestinal: (70-80% of pancreatic secretion) Hormonally mediated when gastric chyme enters duodenum. Both components of pancreatic juice stimulated (enzymes + HCO3- juice flows into duodenum)

Answer 124

- Bicarbonate secretion is controlled by release of hormone SECRETIN which binds and upregulates cAMP intracellularly -> increased transportation across membrane - Enzyme secretion is controlled by vagal reflex and by hormone CHOLECYSTOKININ (CCK) which binds to acinar cells and change intracellular Ca2+ and Phospholipase C (PLC) -> fusion of zymogen vesicles with membrane

Answer 125

- S cells in the duodenum ahve proton receptors and detect the high H+ concentration in acidic chyme - They produce secretin into the blood and in the pancreas it binds to receptors in duct cells - Binding leads to secretion of bicarbonate which reacts with chyme and increases pH - Increase in pH = less H+ so S cells are no longer stimulated

Answer 126

- Presence of peptides and fat in the chyme in the duodenum activate receptors in C cells (or I cells) Note: also stimulates by vagus nerve (parasympathetic) - CCK secreted into blood and reaches pancreas, where it binds to acinar cells - Acinar cells stimulates to produce enzyme secretion (pro-enzymes and trypsinogen inhibitor) - Enzymes break down the peptides and fat -> C cells no longer stimulated (may be other mechanisms involved)

Answer 127

- CCK alone -> no effect on bicarbonate secretion - CCK can markedly increase bicarbonate secretion that has been stimulated by secretin - Vagus nerve has a similar effect to CCK (i.e. enhances production in presence of secretin) - Secretin has NO EFFECT of enzyme secretion

Answer 128

- Consists of the colon, cecum, eppendix, rectum and anal canal - Cecum is a blind pouch just distal to the ileocecal valve. Larger in herbivores - Appendix is a thin, finger-like extension of the cecum. Not physiologically relevant in humans

Answer 129

- 1.5m long, 6cm diameter

Answer 130

- Reabsorption of electrolytes and water | - Elimination of undigested food and waste

Answer 131

- Ascending colon is on right side of the abdomen and runs from the cecum to the hepatic flexure (turn of colon, by liver) - Transverse colon runs from the hepatic flexure to the splenic flexure (turn of colon, by spleen). - Hangs off the stomach, attached by a wide band of tissue called the greater omentum - Attached at posterior by mesocolon - Descending colon runs from splenic flexure to the sigmoid colon - Sigmoid (S-shaped) colon runs from descending colon to the rectum

Answer 132

- Proximal colon (ascending and first part of transverse) supplied by the middle colic artery (a branch of the superior mesenteric artery) - Distal third of transverse and descending supplied by the inferior mesenteric artery Reflects embryological division between the midgut and hidgut. Due to the two different supplies, the area near the splenic flexure or transverse colon is most susceptible to ischaemia

Answer 133

- Peritoneum carries fatty tags (appendices epiploicae). Unknown purpose, suggested that it has a protective function against intra-abdominal infection - Muscle coat has 3 thick longitudinal bands (taeniae coli) giving a pouched appearance (haustra). Taenia coli necessary for large intestine motility. Taenia coli are shorter than large intestine -> haustra form.

Answer 134

- Colon absorbs electrolytes and water - More in proximal colon - Na+ and Cl- absorbed by exchange mechanisms and ion channels - Water follows by osmosis - K+ moves passively into lumen - Large intestine can reabsorb approx 4.5L water (usually 1.5L with most reabsorbed in small intestine). If there is more fluid than threshold -> diarroea

Answer 135

- Dilated distal portion of the alimentary canal - Histology similar to the colon, but distinguished by transverse rectal folds in its submucosa (allows faeces storage) and the absence of taenia coli in its muscularis externa - Terminal portion is anal canal. Surrounded by internal (circular muscle) and external (striated muscle) anal sphincters - Internal is smooth and autonomic control, External is striated and voluntary control.

Answer 136

- Mucosa appears smooth at the gross level because it has no villi (smaller SA than small intestine) - Enterocytes have short, irregular microvilli and primarily concerned with resorption of salts - (Water is absorbed passively, as it follows electrolytes -> more solid gut contents) - Crypts have more goblet cells to secrete mucus to allow more solid contents to keep moving, with numbers increasing distally toward the rectum. Stimulated by ACh from parasympathetic NS and enteric - No paneth cells as bacteria are necessary - Enteroendocrine cells are rarer than in small intestine - Glycocalyx does not contain digestive enzymes

Answer 137

- (like small intestine), muscularis externa consists of an inner circular and outer longitudinal layer - Circular muscles segmentally thickened - Longitudinal layer concentrated in 3 bands (taenia coli) between the taenia, the longitudinal layer is thin. Taenia coli is continuous until the rectum and anal canal - Bundles of muscle from the taenia coli penetrate the circular layer at irregular intervals - Taenia is shorter than circular muscle layer so lead to ovoid segments called haustra which can contract individually - Requires due to more complicated movement (than small intestine) to allow further absorption

Answer 138

- COLONIC contractions (kneading process): minimally propulsive, 5-10cm/hr at most. Promotes absorption of electrolytes and water - In proximal colon 'antipropulsive' patterns dominate to retain chyme - In transverse and descending colon, localised segmental contractions of circular called HAUSTRAL contractions cause back and forth mixing - Hautral movements are short, propulsive movements every 30 mins. Increase in frequency after a meal - MASS MOVEMENT: 1-3 times daily, resembles peristaltic wave. Can propel contents 1/3 - 3/4 of length of large intestine in a few seconds. - Food containing fibre (indigestible material) promoted rapid transport through the colon

Answer 139

- Parasympathetic: Stimulates colon Ascending colon and most of transverse innervated by the vagus nerve. More distal innervated by the pelvic nerves. - Sympathetic: Inhibits colon Pre-ganglionic cell bodies at lower thoracic and upper lumbar spinal cord - External anal sphincter controlled by somatic motor fibres in the pudendal nerves - Enteric nervous system: Important. E.g. no enteric intramural ganglia -> Hirschsprung's disease. Myenteric plexus ganglia is concentrated below the taenia coli. - Presence of food in stomach can stimulate mass movement - could be neural or hormonal (unsure). - Hormonal/paracrine control e.g.aldosterone promotes Na+ and water absorption (by synthesis of Na+ ion channel, and Na+/K+ pump)

Answer 140

- Rectum filled with faeces by mass movement in the sigmoid colon - Stores stool until convenient to void (on transverse rectal folds) - Defecation reflex is controlled primarily by the sacral spinal cord - both reflex and voluntary actions - Reflex to the sudden distension of walls of rectum: pressure receptors send signals via myenteric plexus to initiate peristaltic waves in descending, sigmoid colon and rectum. Internal anal sphincter is inhibited (so it's open). - Enteric nervous system has a weak intrinsic signal which can be augmented by autonomic reflex - External anal sphincter under voluntary control - If urge is resisted, the sensation subsides - Last few centimetres of rectum is 'social part', and it can tell the difference between solid, liquid and gas - important in knowing what can be passed appropriately in what circumstances. (steatorrhoea - can't tell difference between gas and oil)

Answer 141

- 150g/day for an adult - 2/3 water - Solids: cellulose, bacteria, cell debris, bile pigments, salts (K+ - as passively diffuses into lumen) - Bile pigment gives colour - Bacterial fermentation gives odour

Answer 142

- Diverse, highly metabolically active community - All mammals have a symbiotic relationship with gut microbial community (microbiome) - Stomach and small intestine have few bacteria (protected by Paneth cells and acid) - Large intestine has many - essential for normal function - Average adult human comprises of about 1.5kg of live bacteria, with active biomass of an organ system

Answer 143

- Synthesize and excrete vitamins e.g. Vitamin K - germ free animals can have clotting problems - Prevent colonization by pathogens by competing for attachment sites or for essential nutrients - Antagonize other bacteria through production of substances which inhibit or kill non-indigenous species - Stimulate the production of cross-reactive antibodies. Antibodies produced against components of the normal flora can cross react with certain related pathogens, and thereby prevent infection/invasion - Stimulate development of certain tissues, including cecum and lymphatic tissues - Fibre (indigestible carbohydrate) can be broken down by colonic bacteria - produces short chain fatty acids which can regulate gut hormone release, absorbed and used as an energy source or influence functions e.g. food intake or insulin sensitivity directly

Answer 144

- Most prevalent are Bacteroides: Gram negative, anaerobic, non-sporeforming bacteria. Implicated in the initiation of colitis and colon cancer - Bifidobacteria: Gram positive, non-sporeforming, lactic acid bacteria. Thought to prevent colonization by potential pathogens ('friendly')

Answer 145

- drug metabolism - insulin resistance - bile acid metabolism - lipid metabolism - obesity (extaction of more)

Answer 146

Stool substitute transplant therapy | - repopulates the gut with bacteria which may help to fight the infection

Answer 147

- Process whereby atoms or molecules intermingle because of their random thermal motion. - Occurs rapidly over microscopic distances, but slowly over macroscopic distances

Answer 148

- Multicellular organisms evolve circulatory systems to bring individual cells within diffusion range - The cell membrane acts as a diffusion barrier, enabling cells to maintain cytoplasmic concentrations of substances different from their extracellular concentrations - Lipid soluble (non-polar) molecules can cross more easily than water soluble (polar) molecules

Answer 149

Water moving from a hypotonic region to a more hypertonic region

Answer 150

- Paracellular: through tight junctions and lateral intercellular spaces - Transcellular: through the epithelial cells

Answer 151

``` Passive: - Simple diffusion - Facilitated diffusion Active: - Active transport ``` 2 types of transport proteins involved: (allow faster transport) - Channel proteins form aqueous pores allowing specific solutes to pass across the membrane - Carrier proteins bind to the solute and undergo a conformational change to transport it across the membrane

Answer 152

Ion channels have hydrophobic surface joining the lipid bi-layer, and hydrophilic surface forming an ion-selecting filter in the aqueous pore. Ion channels can be gated in different ways: - Voltage gated - Ligand-gated (extracellular ligand) - Ligand-gated (intracellular ligand) - Mechanically gated

Answer 153

- Uniport (movement of one molecule) - Coupled transport: (movement of two different molecules) - Symport: transported and co-transported molecule move in same direction - Anti-port: transported and co-transported molecule move in opposite directions

Answer 154

Primary active transport: - e.g. Na+/K+ ATPase, H+/K+ ATPase - Liinked directly to cellular metabolism (uses ATP to power the transport) Secondary active transport: - e.g. SGLT-1 co-transport, HCO3-/Cl- counter transport, NA+/H+ counter transport - Derives energy from the concentration gradient of another substance that is actively transported

Answer 155

Enhances the rate of substance can flow down its concentration gradient. This tends to equilibrate the substance across the membrane and doesn't require energy. E.g. GLUT-5, GLUT-2

Answer 156

- 99% of water presented to GI tract is absorbed - The absorption of water is powered by the absorption of ions - The greatest amount of water is absorbed in the small intestine, especially the jejenum (approx. 8L/day) - Approximately 1.4L/day absorbed in large intestine - Many ions slowly absorbed by passive diffusion - Ca2+ and iron are incompletely absorved - and this is regulated

Answer 157

- Diet - 2L - Saliva - 1.2L - Gastric secretions - 2L - Bile - 0.7L - Pancreas - 1.2L - Intestinal 2.4L

Answer 158

The reabsorption of water against the osmotic gradient in the intestines.

Answer 159

Water absorption is driven by Na+ transport from lumen into enterocyte and becomes more efficient as you travel down the intestine: - Counter-transport of Na+ in exchange for H+ in proximal bowel (Na+/H+) - Co-transport of Na+ with amino acids and monosaccharides in jejenum - Co-transport of Na+ with Cl- in the ileum - Na+ ion channels (colon) - K+ diffuses in via paracellular pathways in small intestine and leaks back out between cells in the colon (passive) - CO2 and H2O react to form H+ (for Na+/H+) and HCO3- (CL-/HCO3-) - [Na+] increase in cell -> Na+/K+ ATPase actively transports Na+ into lateral intercellular spaces to maintain low Na+ conc. in cell - Cl- and HCO3- transported into intercellular spaces due to electricl potential created by the Na+ transport - High conc of ions = hypertonic fluid -> osmotic flow of water into intercellular spaces -> increased hydrostatic pressure which moves the water and ions into the blood stream (to be carried away)

Answer 160

- Duodenum and Ileum absorb Ca2+ - Ca2+ deficient diet increases gut's ability to absorb - Vit D and parathyroid hormone stimulate absorption - Diet 1-6g/day, secreting/losing 0.6g and absorbing 0.7g

Answer 161

- Low intracellular [Ca2+] approx. 100nM (but can increase 10-100 fold during various cellular functions) - High extracellular fluid [Ca2+] approx. 1-3mM. Plasma [Ca2+] approx. 1-3mM, and luminal [Ca2+] varies in mM range.

Answer 162

- Calcium is carried across the apical membrane by: - Intestinal calcium-binding protein (IMcal) by facilitated diffusion - Ion channel - BUT Ca2+ acts as an intracellular signalling molecule so a low [Ca2+] concentration must be maintained. Ca2+ binds to calbindin in cytosol (preventing its actions as an intracellular signal. - Ca2+ is pumped across basolateral membrane by plasma membrane Ca2+ ATPase (PMCA) against its concentration gradient. - PMCA has a high affinity for Ca2+ but low capacity and it maintains the very low concentrations of Ca2+ normally observed within a cell - Ca2+ also pumped across basolateral membrane by plasma membrane Na+/Ca2+ exchanger against concentration gradient. - The Na+/Ca2+ exchanger has a low affinity for Ca2+ but a high capacity (requires larger concentrations of Ca2+ to be effective)

Answer 163

- Essential for normal Ca2+ absorption | - Deficiency causes rickets, osteoporosis

Answer 164

- Enhances the transport of Ca2+ through the cytosol - Increases the levels of calblindin - Increases rate of extrusion across basolateral membrane by increasing the level of Ca2+ ATPase in the membrane

Answer 165

- Can act as an electron donor and and electron acceptor - Essential for oxygen transport (red blood cells) - Oxidative phosphorylation (in the mitochondrial transport chain) BUT: iron is toxic in excess, but the body has no mechanism for actively excreting iron. So it needs to be absorbed quickly as required, but also be limited.

Answer 166

Adults ingest approx 15-20mg/day but absorbs only 0.5-1.5mg/day

Answer 167

- Iron present in the diet as: - Inorganic iron (Fe3+ ferric, Fe2+ ferrous) - As part of heme (haem) group (haemoglobin, myoglobin and cytochromes) - Cannot absorb Fe3+, only Fe2+ - Vit C reduces Fe3+ to Fe2+ - Fe3+ insoluble salts with: hydroxide, phosphate, HCO3- - Heme is a smaller part of the diet, but more readily absorbed (20% of presented, rather than 5%)

Answer 168

- Dietary heme is highly bioavailable - Heme is absorbed intact into the enterocyte - Evidence that this occurs via the heme carrier protein 1 (HCP-1), and via receptor mediated endocytosis - Fe2+ liberated Heme oxygenase HCP-1 bound to heme ----> Fe2+

Answer 169

- Duodenal cytochrome B (Dyctb) catalyses the reduction of Fe3+ to Fe2+ in the process of iron absorption in the duodenum - Fe2+ transported via divalent metal transporter 1 (DMT-1), a H+ coupled co-transporter - Fe2+ binds to unknown factors, carried to basolateral membrane, moves via ferroportin (FP) ion channel into blood - In the blood hephaestin (HP) is a transmembrane copper-dependent ferroxidase that converts Fe2+ to Fe3+ - Fe3+ binds to apotransferrin (in blood), travels in blood as transferrin - Hepcidin, the major iron regulating protein, suppresses ferroportin function to decrease iron absorption (negative feedback)

Answer 170

- Fe2+ in the cell binds to apoferritin in cytosol to form ferritin micelle - Ferritin is a globular protein complex. Fe2+ is oxidised to Fe3+ which crystallises within protein shell - A single ferritin molecule can store up to 4000 iron ions - In excess dietary iron absorption, produce more ferritin

Answer 171

- Irreversible binding of iron to ferritin in the epithelial cells - Iron/ferritin is not available for transport into plasma - Iron/ferritin is lost in the intestinal lumen and excreted in the faeces - Increase in iron concentration in the cytosol increases ferritin synthesis

Answer 172

- Organic compounds that cannot be manufactured by the body but vital to metabolism - Passive diffusion predominant mechanism - Fat soluble vitamins (A, D, E, K) transported to brush border in micelles. Vit K is taken up by active transport - Specific transport mechanisms for Vitamin C (ascorbic acid), folic acid, Vitamin B1 (thiamine), Vitamin B12

Answer 173

- Liver contains a large store (2-5mg) - Impaired absorption of Vit B12 retards the maturation of red blood cells. PERNICIOUS ANAEMIA - Most Vit B12 in food is bound to proteins

Answer 174

- In the stomach, low pH and the digestion of proteins by pepsin releases free Vit B12 BUT B12 is easily denatured by HCL - Bind to R protein (haptocorrin) released in saliva and from parietal cells - R proteins are digested in the duodenum (releasing B12)

Answer 175

- In the duodenum R proteins are digested releasing Vit B12 - Vit B12 binds to Intrinsic factor, a glycoprotein secreted by parietal cells - VitB12-IF is resistant to digestion - No IF then no absorption of Vit B12 - Vit B12-IF complex binds to cubilin receptor and is taken up in distal ileum (unknown mechanism - thought to involve receptor-mediated endocytosis) - Once inside the cell Vit B12-IF complex broken (possible in mitochondria) - B12 binds to protein transcobalamin II (TCII), crosses basolateral membrane by unknown mechanism - B12-TCII travels to the liver - TCII receptors on cells allow them to uptake complex - Proteolysis then breaks down TCII inside the cell

Answer 176

- History - Examination - Investigations: - Simple - blood tests, blood pressure, pulse, urine dipstick - Complex blood test - Simple imaging - Cross sectional imaging - Invasive test

Answer 177

(SOCRATES) - Site - Onset - Character - Radiation - Associated Symptoms - Timing - Exacerbating/relieving factors - Severity

Answer 178

- Initially poorly located - Onset usually over hours (can be very quick) - Usually more of a dull ache - May have associated GI symptoms

Answer 179

Foregut: - Oesophagus, stomach, pancreas, liver, gallbladder and duodenum (first part) Midgut: - Duodenum (last 2/3) to mid transverse colon Hindgut: - Transverse colon to the anal canal - Retroperitoneal organs (e.g. kidney, pancreas) - Diaphragm (e.g. liver, gallbladder or duodenum)

Answer 180

- Foregut - Epigastrium - Midgut - Umbilical region - Hindgut - Suprapubic - Retroperitoneal - Back pain - Diaphragm - Shoulder tip pain

Answer 181

- Oesophagus - Epigastric region - Stomach - Left hypochondriac region - Small Bowel - Umbilical region - Large Bowel - Umbilical and Hypogastric region - Appendix - Right Iliac region - Hepatic pain - Right hypochondriac region - Biliary pain - Right hypochondriac region - Pancreatitis - Epigastric region

Answer 182

- Sharp and very severe - Localised initially, then becomes more generalised - Worse on movement - Guarding (tension of muscle on palpation) - Rebound tenderness

Answer 183

Muscular contractions of a hollow tube in an attempt to relieve an obstruction by forcing content out. It may be accompanied by vomiting and sweating. Occurs in hollow tubes e.g. - Ureter - Urethra - Colon - Bile ducts - Pancreatic ducts

Answer 184

- Renal pain - Flank to groin - Bladder - Suprapubic - Pneumonia - Upper quadrant - Heart attack - Epigastric - Pelvic Inflammatory disease - Lower abdomen - Musculo skeletal - Anywhere

Answer 185

1. Right hypochondriac region 2. Epigastic region 3. Left hypochondriac region 4. Right lumbar region 5. Umbilical region 6. Left lumbar region 7. Right Iliac region 8. Hypogastric region 9. Left Iliac region 1 2 3 4 5 6 7 8 9

Answer 186

- Very variable presentation - Abdomen pain localised to the epigastrium and radiating to the back - Nausea and vomiting is common - Patient is acutely unwell and in shock - May have organ failure (chest/kidney) - May also have evidence of jaundice/cholangitis - Potentially VERY unwell

Answer 187

- Full blood count - Urea and electrolytes - Inflammation markers (C reactive protein (CRP), erythrocyte sedimentation rate (ESR) - Liver function tests - Clotting - Calcium - Glucose

Answer 188

- Amylase - Lipase - Triglycerides

Answer 189

- Chest X-ray - Abdominal X-ray - Ultrasound - CT scan - MRCP (magnetic resonance cholangiography/pancreatography)

Answer 190

ERCP - Endoscopic retrograde Cholangio-pancreatography

Answer 191

(GET SMASHED) - Gallstones - Ethanol - Trauma - Steroids - Mumps - Autoimmune - Scorpion venom - Hyperlipidaemia/hypercalcaemia - ERCP - Endoscopic retrograde Cholangio-pancreatography - Drugs (azathioprine, NSAID, furosemide, sulphonamides)

Answer 192

1. Gallstones | 2. Ethanol

Answer 193

- Pancreatic necrosis - Fluid collections -> mature into pseuduocysts - Splenic vein thrombosis/pseudoaneurysm - Chronic pancreatits

Answer 194

- Hypovolaemia - Hypoxia - Hypocalcaemia - Hypercalcaemia - DIC (disseminated intravascular coagulation) - Multiple organ failure

Answer 195

- Oesophageal cancer - Colon cancer - Pancreatic cancer

Answer 196

- Cancer: a disease caused by uncontrollable division of abnormal cells in a part of the body - Primary: arising directly from the cells in an organ - Secondary/Metastasis: spread from another organ, directly or by other means (blood/lymph)

Answer 197

Epithelial cells: - Squamous -> squamous cell carcinoma - Glandular epithelium -> adenocarcinoma Neuroendocrine cells: - Enterochromaffin cells -> carcinoid tumours - Interstitial cells of Cajal -> Gastrointestinal stromal tumours Connective tissue: - Smooth muscle -> Leiomyoma/leiomyosarcomas - Adipose tissue -> lipomas

Answer 198

Adenocarcinoma

Answer 199

- From metaplastic columnar epithelium - Lower 1/3 of oesophagus - Related to acid reflux - More common in more developed world

Answer 200

- From normal oesophageal squamous epithelium - Upper 2/3 - Acetylaldehyde pathway - More common in less developed world

Answer 201

Examining the interior of a hollow organ (e.g. oesophagus) or cavity of the body using an endoscope.

Answer 202

1. Chronic exposure to acid 2. Oesophagitis (inflammation) - injury, ongoing inflammation, cytokine drive 3. Barrett's Oesophagus (metaplasia: stratified squamous -> simple columnar) 4. Dysplasia 5. Carcinoma (neoplasm)

Answer 203

- All Barrett's: 0.12% per year (4% -> low grade dysplasia, 1.3% -> high grade dysplasia) - Low grade dysplasia: 0.5% annual risk of cancer (1.5% -> high grade dysplasia) - High grade dysplasia: 5-30% annual risk of cancer

Answer 204

Metaplasia: reversible change of one differentiated cell type to another Dysplasia: expansion in immature cell types replacing more mature cells

Answer 205

(Seattle protocol) - 4 biopsies every 1cm along segment - Barrett's oesophagus (no dysplasia): every 3-5 years - Low grade dysplasia: every 6 months until no dysplasia - High grade dysplasia: If flat then radiofrequency ablation (removal) (e.g. HALO), if nodular then endoscopic mucosal resection then HALO

Answer 206

- Family history - Inherited conditions e.g. FAP (familial adenomatous polyposis), HNCCP (hereditary non-polyposis colorectal cancer), Lynch syndrome - Uncontrolled ulcerative colitis (for a long time) - Age (most significant) - Previous polyps

Answer 207

1. Normal epithelium - > APC mutation (adenomatous polyposis coli) 2. Hyperproliferative epithelium . Aberrant cryptic foci -> COX-2 overexpression) 3. Small adenoma (e.g. polyps) - > K-ras mutation 4. Large adenoma - > p53 mutation, -> Loss of 18q 5. Colon carcinoma NOT a single gene process - a sequence of genetic errors. Therefore not simple Mendelian inheritance.

Answer 208

- Most common: Asymptomatic (possible incidental anaemia) - Change in bowel habit: Diarrhoea, constipation (usually very late stage due to obstruction) - Blood in stool (black or altered and mixed with stool - more likely to be colon) - Acute intestinal obstruction (very late sign - bad prognosis)

Answer 209

- Rectal bleeding with anal symptoms e.g. itch, soreness/discomfort, external lump, prolapse - Change in bowel habit to harder or less frequent (constipation) - Abdominal pain in the absence of obstruction These patients have the same risk of cancer as age-matched controls.

Answer 210

+ - cheap - easy - quick - - Sensitivity for obstruction 77% - Specificity for obstruction 50%

Answer 211

+ - quick - easy - see large lesions - - may miss smaller lesions - no tissue (e.g. sample) - no therapy

Answer 212

+ - reasonable sensitivity and specificity - - time intensive - technically demanding - unacceptable to patients (not used very much)

Answer 213

- Barium liquid is instilled into the large interesting through the anus - An X-ray is taken (with the barium showing up white)

Answer 214

Exam where a colonoscope (long, flexible tube) is inserted into the rectum and the camera on its tip allows imaging of the colon.

Answer 215

+ - safe - relatively quick - high sensitivity - able to obtain tissue - - 2 days of iatrogenic diarrhoea - small risk of perforation (

Answer 216

- Dye given which tags the stool using Bismuth - CT scan done - Computer aided subtraction creates images of the inside of the colon

Answer 217

+ - quick and easy - reduced bowel prep = more tolerable - as good as colonoscopy for lesions >6mm - - unable to obtain tissue - unable to remove lesions

Answer 218

'silent killer' - non-specific symptoms - Virchow's triad: - Pain 70% - Anorexia 10% - Weight loss 10%

Answer 219

- Abdominal pain - Depression - Glucose intolerance

Answer 220

- Weight loss - Jaundic - Ascites (fluid filling peritoneal cavity) - Obstructed gall bladder (-> leading to jaundice)

Answer 221

- Outcome is poor: - only 20% suitable for resections - surgery (remove pancreas and gall bladder) is curative in 20-25% of cases - 1 year survival 18% - 5 year survival 2%

Answer 222

- Smoking - Drinking. - Obesity - Genetics: especially rare conditions e.g. MEN (multiple endocrine neoplasia)

Answer 223

The qualitative and quantitative information about the different microbes present in a system (who and how many?)

Answer 224

The functions that these microbiota have, (e.g. bile metabolism) their gene catalogue.

Answer 225

Either 'gain of function' or DNA based approach to create gene catalogues used to define the microbiome.

Answer 226

Creation of 16S rRNA gene inventories, used to define the microbiota.

Answer 227

A catalogue of the metabolites in a sample (in a tissue or isolate).

Answer 228

- Genetics - Environment - Microbiome (host specific- dependent on genetics and environment e.g. diet)

Answer 229

- diet - Antibiotics - pregnancy - surgery (particularly abdominal e.g. gastric bypass)

Answer 230

160 different species

Answer 231

- BOTTOM UP: (Metataxonomics, metagenomics) Flow of information is from DNA -> RNA -> protein -> metabolite. Find out what is in the sample and then what metabolites they produce. E.g. faeces sample. - TOP DOWN: (Metabolomics - sample tissue/cell, metabonomics - sample urine, blood etc). Look at the metabolite pool.

Answer 232

- Take a sample e.g. faeces - DNA/RNA extracted from all microbes present in sample - Amplify SSU rRNA (16S rRNA gene or other house keeping gene present in all microbes) using PCR - Compare 16S rRNA to database to identify microorganisms (each species has slightly different coding sequence) e.g. using Illumina MiSeq, or Nanopore MinION Function: - Identify population/community dynamics - Diversity indices (shown by DNA) - Microbial biomarkers - RNA shows metabolic activity - Antibiotic metabolism

Answer 233

- Some people born sterile, others not - Initially colonised by mother - depends of birth (vagina or caesarean) e.g. skin bacteria like staphilococcus aureus, or vaginal bacteria e.g. lactobacillus. Also breast-fed or formula etc. - If born preterm there are signals in the gut microbiome, or if antibiotics given there will be an effect - After 3 years the microbiome is relatively stable

Answer 234

Large intestine contains about 1-2kg of microbial biomass.

Answer 235

- Viruses around 1200 viral genotypes (limited info) - Eukaryotes: very few studies - Bacteria:160 species per person and possible >7000 strains. >1000 species in total.

Answer 236

- Bacterioides | - Firmicutes (clostridia)

Answer 237

- Defence: bacterial antagonism - Priming of mucosal immunity - Peristalsis - Metabolism of dietary carcinogens - Synthesis of B and K vitamins - Epithelial nutients (e.g. short chain fatty acids e.g. butyrate) - Conversion of prodrugs - Utilisation of indigestible products (CH2O)n

Answer 238

- Turn procarcinogens -> carcinogens - Overgrowth syndromes - Opportunism e.g. translocation after surgery - Essential in irritable bowel disease (IBD) (controversial) : - Utilisation of indigestible (CH2O)n could lead to obesity - Role in insulin resistance and non alcoholic fatty liver disease

Answer 239

- Inflammatory bowel disease - Colon cancer - Heart disease - Depression - Non-alcoholic fatty liver disease - Obesity - Diabetes - Asthma/eczema

Answer 240

Change the metabolism of drugs.

Answer 241

Mutualism = beneficial for both organisms involved E.g. Faecal microbiota transplantation (FMT) for clostridium difficile associated diarrhoea (CDAD)

Answer 242

Relationship where one organism recieves a benefit, and the other is unaffected.

Answer 243

Relationship where one organism benefits and the expense of the other (i.e. host is harmed) E.g. Helicobacter pylori or C. difficile

Answer 244

Microbes which cause inadvertent damage to the host, but is not evolved to do so. (collateral damage). Often pathology can't be pinned to one pathogen.

Answer 245

- Bacterial proteases, and Lipopolysaccharides and endotoxins - Compromise the tight junction integrity allowing translocation of molecules in the lumen which can lead to inflammation. - Persistant exposure of liver to endotoxins causes low level chronic inflammation-> fat deposition -> non-alcoholic steatohepatitis -> non-alcoholic fatty liver diease -> cirrhosis and fibrosis - Bacteria also affect the levels of LPS and endotoxin

Answer 246

- CPT-11 is a molecule in chemotherapy which is cleaved and after having its effect on the tumour, the liver adds a sugar group on it (to prevent damage during excretion) - BUT some gut microbes cleave off the sugar group (using glucuronidase) to use as an energy source leading to diarrhoea -> patient taken off of chemotherapy - Drug developed which inhibited only the microbial glucuronidase -> patients can use chemotherapy for longer

Answer 247

- Important to maintain cholesterol levels - Necessary for lipid and vitamin absorption in small intestine - Removal of xenobiotics (foreign)/drugs.endogenous waste products e.g. cholesterol metabolites, adrenocortical and other steroid hormones.

Answer 248

- Water 97% - Bile salts - Inorganic salts - Bile pigments (Bilirubin, bilivirden) - Fatty acids - Lecithin - Fat - Cholesterol - Other e.g. drug metabolites, trace metals (alkaline electrolyte solution)

Answer 249

- 500ml produced a day - Green/yellow colour due to the glucoronides of bile pigments - 60% bile is secreted by hepatocytes - 40% secreted by cholangiocytes (biliary epithelial cells) - Bole drains from the liver, through bile ducts, into duodenum at the duodenal papilla

Answer 250

- 40% bile secreted choliangocytes - Alters pH, fluidity and modifies bile as it flows through - H2O drawn into bile (osmosis through paracellular junctions) - Luminal glucose and some organic acids are also reabsorbed - HCO3- and Cl- actively secreted into bile by CFTR mechanism (cystic fibrosis transmembrane regulator) - Cholangiocytes contribute IgA by exocytosis

Answer 251

- Bile flow is closely related to the concentration of bile acids and salts in the blood - Biliary excretion of bile salts and toxins is performed by transporters on apical surface of hepatocytes and cholangiaocytes - These biliary transporters also govern the rate of bile flow - Dysfunction of the transporters is a cause of cholestasis - Main transporters include; - Bile salt excretory pump (BSEP) - MDR related proteins (MRP1 and MRP3) - products of the familial intrahepatic cholestasis gene (FIC1) and multidrug resistance genes (MDR1 and MDR3)

Answer 252

- (controlled by ABCB11 gene) - Active transport of bile acids across hepatocyte canalicular membranes into bile - secretion of bile acids is a major determinant of bile flow

Answer 253

Mediates canalicular excretion of xenobiotics and cytotoxins

Answer 254

Encodes a phospholipid transporter protein that translocated phosphatidylcholine from inner to outer leaflet of canalicular membrane

Answer 255

- Na and K salts of bile acids - Conjugated in the liver to glycine and taurine - Bile acids are synthesised from cholesterol - There are four bile acids in humans: - 2 primary acids: (formed in the liver) cholic acid, chenodeoxycholic acid - 2 secondary acids: (primary converted by colonic bacteria) deoxycholic acid, litocholic acid

Answer 256

- Reduce suface tension of fats | - Emulsify fat prepatory to its digestion/absorption

Answer 257

Bile salts are ampiphilic: - one surface = hydrophilic domains (faces OUT). Other surface = hydrophobic domains (faces IN) - free fatty acids and cholesterol are inside the micelle - micelles are transported to the gastrointestinal tract for absorption

Answer 258

Because of detergent-like actions, bile salts are potentially cytotoxic in high concentrations. - may cause bile acid diarrhoea (BAD)

Answer 259

- Biliary ducts drain into left and right hepatic ducts - They join to form the common hepatic duct - Common hepatic duct exits liver and joins the cystic duct (exiting gallbladder) - Forms the common bile duct - Common bile duct enters the duodenum through ampulla of vater which is controlled by the sphincter of oddi

Answer 260

- Between meals, the sphincter of oddi is closed so no bile enters the duodenum - Bile is stored in the gallbladder - When eating, entry of food into the stomach causes release of cholecystekinin - CCK causes opening of the sphincter and contraction of the gall bladder to release bile into the duodenum Note: - the more fatty food eaten the more the gallbladder will contract. - gallbladder stones - more pain after eating because of contraction

Answer 261

- Bile salts are not reabsored -> more than 5% of bile enters the colon - Increased fat in stool (as less bile salt micelles continue into the colon instead of being reabsorbed) - Malabsorption of fat soluble vitamins (A,D,E,K)

Answer 262

- 3g bile salt pool re-cycles about 2x per meal (6-8 times a day)

Answer 263

- Stored bile (50ml), released after meal for fat digestion - Acidifies bile - Concentrated bile by H2O diffusion following net absorption of Na+, Cl-, Ca2+ and HCO3-. (intra-cyctic pH). Gall bladder can reduce volume of its stored bile by 80-90%

Answer 264

(e. g. cancer, gallstones) - Periodic discharge of bile from gall bladder aids digestion BUT is NOT essential - Normal health and nutrition exist with continuous slow bile discharge into duodenum - Avoid food with high fat content - after eating may feel uncomfortable as bile is less concentrated (to digest fats)

Answer 265

- Yellow pigment produced in various ways: - 75% from Haemoglobin breakdown (in spleen) - 22% from catabolism of other haem proteins - 3% from ineffective bone marrow erythropoiesis

Answer 266

- It is insoluble in water, so binds to albumin and travels in the blood - Albumin-bilirubin complex dissassociates in the liver - Free bilirubin enters hepatocytes and binds to cytoplasmic proteins to be conjugated to glucoronic acid (by UDPGT/glucuronyl transferase from smooth ER) - Diglucoronide-BR complex is more soluble than free BR - It is transported across the concentration gradient into bile canuliculi and into the GIT

Answer 267

Total BR = Free BR (unconjugated) + Conjugated BR

Answer 268

- Bacterial action on bilirubin in intestines form Urobilinogen - About 50% of urobilinogen is reabsorbed and taken up via the portal vein to the liver, enters circulation and is excreted by the kidney (urine) - The GIT mucosa is impermeable to conjugated BR, but is permeable to unconjugated BR and urobilinogens (therefore some unconjugated BR enters the enterhepatic circulation) - Some urobilinogens pass through in stool as Stercobilinogen

Answer 269

Oxidised to stercobilin which is brown (giving faeces its colour)

Answer 270

Cessation of blood flow.

Answer 271

- Excess bilirubin in blood (>34-50 microM/L) | (Normal level

Answer 272

- Pre-hepatic - Hepatic - Post-hepatic/obstruction

Answer 273

- Increased quantity of bilirubin (at the source) - Most common cause: haemolysis (increased break down of red blood cells) - Massive transfusion - Haematoma resorption - Ineffective erythropoiesis - Look for: Haemoglobin drop without overt bleeding. Where liver function is normal. - Tests: Blood film (look for red cell destruction), haptoglobins and LDH tests

Answer 274

- Hepaatocytes not working -> defective uptake, conjugation and/or BR excretion - Liver failure: Can be acute/fulminant or acute on chronic - Causes (many): e.g. Viral Hepatitis, ethanol, autoimmune disease (e.g. PBC, PSC), intrahepatic cholestasis (-> sepsis. treat with TPN, drugs), drugs - If high unconjugated BR - low BR uptake, low BR conjugation - If high conjugated BR - hepatocellular dysfunction, low hepatic BR excretion

Answer 275

- Defective transport of BR by biliary duct system (by physical blockage usually) - E.g. Common bile duct stones, Hepatic/Pancreas.Biliary malignancy, local lymphadenopathy - Can lead to sepsis (cholangitis) - Confirm with CT/MRI/MRCP scan - High conjugated bilirubin - Dark urine, pale stool

Answer 276

- Gilbert's syndrome (benign cause of jaundice) - commonest hereditary cause of increased bilirubin - up to 5% of population - autosomal recessive inheritance - elevated unconjugated BR in bloodstream due to 70-80% reduction in glucuronidation activity of the enzyme UDPGT-1A1 - no serious consequences. Mild jaundice may appear under - exertion, stress, fasting, infections - otherwise usually asymptomatic

Answer 277

When the rate of hepatocytes death > regeneration with various causes. - Acute: rapid development (

Answer 278

- Hyperacute (0-7 days) - Acute (8-28 days) - Subacute (29 days - 12 weeks)

Answer 279

- Most common: (up to 70% of ALF cases) paracetamol overdose (>10g toxicity possible), lower doses potentially hepatotoxic in alcoholics, malnutrition or fasting. - Amanita phalloides (fungi) - Bacillus cereus (bacteria) - Viral hepatitis (B and E - main cause in Far East) - Pregnancy: e.g. acute fatty liver of pregnancy, HELLP, hepatic infarction etc - Idiosyncratic drug reactions - Vascular diseases e.g. ischaemic hepatitis - Metabolic e.g. Wilson's disease

Answer 280

- Increased toxins in blood can cause enecephalopathy and cerebral oedema - Hypoglycaemia (no glycogen breakdown) - Coagulopathy and bleeding - Increased susceptibility to infection - Circulatory collapse, renal failure

Answer 281

- Initially non-specific: malaise (general unease), nausea, lethargy - Jaundice - After variable time period, encephalopathy

Answer 282

- Emergency liver transplant in ONLY therapeutic intervention proven to benefit

Answer 283

- Co-morbitdities and extent of failure may make is unnecessary - Commits patient to lifelong immunosuppression - Expensive - 'Wastes a precious graft' - Operation risk is

Answer 284

- Surface area of GI tract = 400m^2 - Large antigen load from resident microbiota (10^14 bacteria), dietary antigens and exposure to pathogens - Therefore it is in a state of restrained activation - Tolerance vs active immunity response - Immune homeostasis of gut requires presence of bacterial microbiota

Answer 285

- Yeast/fungal infection - Most common is candida albicans - Carried in 50% of individuals - In immunocompromised states e,g, HIV, chemotherapy or treatment with cortiosteroids - Treated with oral anti-fungals e.g. nyastin, or IV antifungals if immunocompromised

Answer 286

- Gram negative microaerophilic rod - Causes gastritis/gastric or duodenal ulcers/gastric carcinoma - BUT 80% of infected individuals are asymptomatic - Investigations: blood antibody, stool antigen, urea breath test, biopsy ureases test - Treatment: 1 week eradication therapy with proton pump inhibitor and clarithromycim/amoxicillun

Answer 287

- Escherichia coli - Shigella - Salmonella - Cholera - Rotavirus - Norovirus - Giardia

Answer 288

- Causes acute gastroenteritis

Answer 289

``` Enterotoxigenix: - Cholera-like toxin - Causes watery diarrhoea Enterohaemorrhagic: - Antigens: EO157/H7 - Toxins: Verotoxin/shigatoxin - Haemolytic uraemic syndrome Enteropathogenic: (EPEC) - common in nurseries (children) Enteroinvasive: - Shigella like illness - Bloody diarrhoea - Megacolon ```

Answer 290

- Colon is colonised by commensal bacteria - Anitbiotics kill many of these bacteria - Allows colonization by Clostridium difficile (no competition) - Production of toxins causes mucosal injury - Neutrophils and red blood cells leak into gut between injured epithelial cells (antibiotic associated colitis)

Answer 291

- Isolate (very contagious) - Stop current antibiotics - Metronidazol and vancomycin - For repeated infection - faecal microbiota transplantation

Answer 292

Physical to prevent invasion: - Anatomical: epithelial barrier, peristalsis - Chemical: enzymes, pH (gastric acid) Commensal bacteria 'Immunological': following invasion - MALT (mucosal associated lymphoid tissue) - GALT (gut associated lymphoid tissue)

Answer 293

- Mucus layer: goblet cells - Epthelial monolayer: tight junctions, antimicrobial peptides, transports IgA - Paneth cells: bases of crypts, defensins, lysozymes

Answer 294

Not organised: - Intra-epithelial lymphocytes - Lamina propria lymphocytes Organised: - Cryptopatches - Peyer's patches - Isolated lymphoid follicles - Mesenteric lymph nodes

Answer 295

Generated lymphoid cells and antibodies: - IgA secretory and interstitial - IgG - IgM - Cell mediated immunity (adaptive and innate)

Answer 296

- In the small intestine, mainly distal ileum - Development requires exposures to bacterial microbiota (50 in last trimester foetus, and 250 by teens) - Organised collection of naive T and B-cells - Covered by follicle associated epithelium (FAE): no goblet cells, no secretory IgA, lack microvilli, infiltrated by T-cells, B-cells, macrophages, dendritic cells - Antigen uptake via M (microfold) cells within FAE - Similar isolated lymphoid follicles elsewhere in GI tract (30,000 in total)

Answer 297

- Follicle associated epithelium - with M cell (antigen sampling) - Underneath is the sub-epithelial dome of dendritic cells. Trans epithelial dendritic cells can sample antigens as well. - Beneath, follicle (B-cells) with T-cell areas (naive T-cells) around the outisde - Lymph vessels connect the patch to lymph nodes

Answer 298

- Antigen sampling by M cells - Transport to antigen presenting cells in sub-epithelial dome - Dendritic cells take up the antigen and process it to present to naive B or T-cells in peyer's patch or transport antigen to lymph nodes. - This results in the development of gut homing markers (once antigen is recognised, defence response returns to gut) - Transfer to mesenteric lymph node to proliferate

Answer 299

- Mature naive B-cells expressing IgM in PPs - Upon antigen presentation class switch to IgA - Influenced by presence of T-cells and epithelium via cytokines - Further maturation to become IgA secreting plasma cells - Populate lamina propria

Answer 300

- IgA secreting cell numbers reflects bacterial load (up to 90% of gut B-cells secrete IgA) - Dimeric structure at mucosal surfaces - Transported by epithelial cells into lumen - Binds luminal antigen - Prevents invasion and adherence - Does not activate complement or cytotoxic lymphocytes - Transported from submucosa to lumen by trancytosis

Answer 301

- Make up one fifth of the intestinal epithelium Made up of: - Conventional T cells (also lamina propria), migrated from other tissues - Unconventional T-cells (innate), resident, express unusual combinations of CD4, CD8, or γδ T cell receptor - Other innate immune cells: Resident NK cells (e.g. NKp44+ NK cells)

Answer 302

- Presentation of antigen (by dendritic cells) within MHC - Co-stimulatory signals on DC - Secretion of cytokines by DC

Answer 303

- Th1 -> cell mediated immunity - Th2 -> normal gut response (humoral immunity) - Th17 -> inflammatory disease? - Treg -> tolerance (normal)

Answer 304

- Lymphocytes proliferate in mesenteric lymph nodes - Enter the lymphatics to thoracic duct - Enter circulation - Selectively home to sites similar to initial priming - Antigen presentation in GALT favours 'gut homing' characterisitics (integrins and chemokine receptors)

Answer 305

α4β7(integrin)-MAdCAM-1 interactions facilitates local gut inflammation

Answer 306

Suppression of immune responses towards antigens Several mechanisms: - Deletion of responding lymphocytes - Anergy - TReg cells

Answer 307

- Inflammatory bowel disease - Coeliac disease - Food allergy

Answer 308

- Villous atrophy - Intolerance to gluten - Pathogenesis: molecules of gluten are absorbed by enterocytes and converted to a deaminated peptide which is recognised by APCs and then activates a naive T cell

Answer 309

- Overall incidence of ulcerative colitis is higher than Crohn's but Crohn's is increasing more - Increasing incidence, especially in young & non-western societies

Answer 310

- Genetic background: > 160 independent IBD susceptibility loci - Immune system: Animal models show germ free environment = no colitis - Environmental factors: smoking, stress, diet, Vitamin D - Faecal stream diversion elleviates Crohn's and reanastomosis triggers recurrence - cause? - Gut microbiota - single organism? expansion or relative contraction? 'functional' changes? changes in mycobiome or virome? - Increased bacteriophage richness and decreased bacterial diversity

Answer 311

- Fusobacteriaceae: biomarker, progression of colorectal cancer - Pasteurellacaea, Veillonellaceae and pathogenic E. coli: link with ulcer formation

Answer 312

- Decrease in butyrate production (Faecalibacterium prausnitzii and Roseburia hominus)

Answer 313

- Nervous stimulation: neurotransmitters released from neurons innervate target cells (intrinsic - enteric, extrinsic - autonomic) - Paracrine: hormones released by cells in the vicinity of the target cell and reach target cell by diffusion - Endocrine: hormones produced by endocrine cells, released into the blood where they reach their targets via the circulation

Answer 314

- Wall of GI tract contains many neurons (2nd only to CNS) - Rich plexus (network) of ganglia (nerve cells + glial cells) interconnected by tracts of fine, unmyelinated nerve fibres - Integrates motor and secretory activities of the GI system - Can function independently of central control - If ANS nerves to gut are cut, many motor and secretory activities continue (as controlled by enteric nervous system)

Answer 315

- Inflammation (ulcerative colitis; Crohn's disease) - Post-operative injury - Irritable bowel syndrome - Ageing (constipation)

Answer 316

- Motility - Blood flow - Water and electrolytes transport - Secretion - Absorption

Answer 317

- Sensory: respond to mechanical, thermal, osmotic and chemical stimuli - Motor: axons terminate on smooth muscle cells of the circular or longitudinal layers, secretory cells of the gastrointestinal tract or gastrointestinal blood vessels - Interneurons: neurons between neurons integrate the sensory input and effector output

Answer 318

- Myenteric Plexus: (Auerbach's plexus) Located between the circular and longitudinal smooth muscle layers. Controls activity of muscularis externa, controls GUT MOTOR function - Submucosal plexus: (Meissner's plexus) Sensing environment within lumen. Blood flow, epithelial and endocrine cell function - Minor plexuses: Including deep muscular plexus (inside circular muscle), and the ganglia supplying biliary system and pancreas

Answer 319

- Regulates smooth muscle, cardiac muscle and glands. - Not accessible to voluntary control - Two branches: Sympathetic and Parasympathetic

Answer 320

Sympathetic: - Cell bodies of pre-ganglionic neurons in thoracic and lumbar spinal cord - Greater and Lesser Splanchnic nerves - T5-11. Innervates fore and midgut - Lumbar splanchnic nerves L1-2 innervate remainder of gut - Neurotransmitter: norepinephrine Parasympathetic: - Cell bodies of pre-ganglionic neurons in brainstem and sacral spinal cord - Cranial nerve X (vagus) - innervates down to transverse colon - Pelvic nerves S2-4 - remainder of colon, rectum and anus - Neurotransmitter: acetyl colon

Answer 321

- Sympathetic: Its activation usually inhibits the activities of the GI system. Inhibits gut motility and secretion, and causes constriction of blood vessels and contracion of sphincters - Parasympathetic: Excitation usually stimulated the activities of the GI tract. Promotes gut motility, secretion and digestion.

Answer 322

- Majority do not directly innervate structures but terminate on neurons in the intramural plexuses - BUT vasoconstrictor sympathetic fibers do directly innervate the blood vessels of the GI tract (coeliac, superor and inferior mesenteric)

Answer 323

Chemo and mechanoreceptors in the wall of the GI tract send impulses to - CNS through splanchnic and vagal afferents - Enteric NS (myenteric and submucosal) by local afferents

Answer 324

- Afferents detect pain, nausea, fullness | - Efferents allow co-ordination from sympathetic and parasympathetic nervous system

Answer 325

- Produced by endocrine cells in the mucosa/submucosa of the stomach, intestine and pancreas - Can act as paracrine or neurocrine factors - Endocrine cells are based further back (close to blood supply) with a finger-like projection up to the lumen. - Can sense nutrients: - K cells: Amino acids, glucose, (long chain) fatty acids -> gastric inhibitory peptide. Proximal intestine - I cells: Amino acids, glucose, (long chain) fatty acids -> cholecystekinin. Proximal intestine - L-cells: Amino acids, glucose, (long and short chain) fatty acids -> GLP-1, GLP-2 and PYY release. Distal intestine and colon

Answer 326

- Regulation of the mechanical processes of digestion (e.g. smooth muscle of GI tract and sphincters, gall bladder) - Regulation of the chemical and enzymatic processes of digestion (e.g. secretory cells located in the wall of the GI tract, pancreas and liver - Control of post-absorptive processes involved in the assimilation of digested food and CNS feedback regulating intake (e.g. GIP stimulates insulin release from pancreatic β-cells, PYY3-36 acts of the CNS to suppress appetite) - Effects on the growth and development of the GI tract (e.g. GLP-2 promotes small intestinal growth)

Answer 327

- Histamine released from stomach wall cells is a key physiological stimulus to HCL secretion by gastric parietal cells - Somatostatin from the stomach can inhibit acid secretion by paracrine mechanisms

Answer 328

- Synthesised in gastric antrum and upper small intestine - Release is stimulated by: - amino acids and peptides in the lumen of the stomach - gastric distension - vagus nerve directly - Gastrin stimulates gastric acid secretion - Release inhibited when pH of stomach falls below pH3

Answer 329

- Synthesised in enterocrine D cells of the gastric and duodenal mucosa, pancreas (also hypothalamus) - Somatostatin is a universal inhibitor (endocrine cyanide) - Release in response to a mixed meal - Inhibits gastric secretion, motility, intestinal nutrient and electrolyte transport, growth and proliferation - Analogues are used to treat neuroendocrine tumours e.g. octreotide - more potent and targetted than somatostatin

Answer 330

- Secreted by S cells of the upper duodenum and jejenum - Major stimulus is the presence of acid in the duodenum (pH falls below 4.5) - Stimulated pancreatic bicarbonate secretion (effect potentiated by CCK) - High concentrations -> inhibition of gastric acid and gastric emptying

Answer 331

- Secreted by cells most densely located in the small intestine - Release stimulated by fat and peptides in the upper small intestine - Independent of the vagus nerve - Function: - stimulates pancreatic enzyme release - delays gastric emptying - stimulates gallbladder contraction - decreases food intake and meal size

Answer 332

- Secreted by mucosal K cells (predominant in the duodenum and jejenum) - GIP released following ingestion of a mixed meal - Stimulates insulin secretion - GIP receptor antagonists reduce postprandial insulin release

Answer 333

- Cells found throughout the mucosa of the terminal ileum, colon and rectum - Released from L cells post prandially (particularly protein) - PYY reduces intestinal motility, gallbladder contraction and pancreatic exocrine secretion - Inhibitor of intestinal fluid and electrolyte secretion - PYY3-36 inhibits food intake

Answer 334

- Increased body fluid osmolality (most potent stimulus). Change of 2-3% induces strong desire to drink - Reduced blood volume - Reduced blood pressure Decrease of 10-15 % in blood volume or pressure required to produce same response.

Answer 335

- Acts on the kidneys to regulate the volume and osmolarity of urine - When plasma ADH is low a large volume of urine is excreted (water diuresis) - When plasma ADH is high a small volume of urine is excreted (anti-diuresis)

Answer 336

- Hypothalamus - Organum vasculosum of the lamina terminalis (OVLT) (above optic chiasm) - Subfornical organ (SFO) (beteen the fornix and hypothalamus)

Answer 337

- Sense changes in body fluid osmolality - Cells shrink or swell in response (expand when plasma is dilute, and vice versa) - Send signals to the ADH producing cells in the hypothalamus to alter ADH release - Same regions seem to regulate thirst

Answer 338

Increased plasma osmolality - Invokes drinking and ADH release - Increased ADH stimulates kidney to conserve water Decreased plasma osmolality - Thirst is suppressed and ADH release decreased - Absence of ADH the kidney excretes more water

Answer 339

- Thirst is decreased by drinking even before sufficient water has been absorbed by the GI tract to correct plasma osmolality - Receptors in the mouth, pharynx, oesophagus seem to be involved - Relief of thirst sensation via these receptors is short lived - Thirst is only completely satisfies once plasma osmolality is decreased or blood volume/arterial pressure is corrected

Answer 340

Evokes the sensation of thirst

Answer 341

- It is increased when blood volume and pressure are reduced - Activates subfornical organ (SFO) neurons - It contributes to the homeostatic response to restore and maintain the body fluids at their normal level

Answer 342

Food intake vs Energy expenditure - Hypothalamus 'decides' food intake and recieves input from: - Ghrelin, Peptide YY and other gut hormones - Neural input from periphery and other brain regions - Leptin (from adipose) - Other (complex integration system)

Answer 343

Paraventricular nucleus Lateral hypo. ( 3rd ) Lateral hypo. Ventromedial Hypo ( Ventricle ) Ventromedial Hypo ( ) Arcuate nucleus( )Arcuate nucleus

Answer 344

- Key brain area involved in the regulation of food intake - Incomplete blood brain barrier which allows access to peripheral hormones - Integrates peripheral and central feeding signals - Two DISTINCT neuronal populations: - Stimulatory (NPY (neuropeptide Y)/Agrp (Agouti-related peptide) neuron) - increases feeding - inhibitory (POMC neuron) - decreases feeding

Answer 345

- POMC neurons produce POMC which is cleaved to produce α-Melanocortin stimulating hormone (MSH) - α-MSH binds to the Melanocortin-4 receptor (MC4R) on paraventricular nuclei - Causes a decrease in food intake - Agrp (agouti-related peptide) is an antagonist which bind to the MC4R and prevent α-MSH binding thereby increasing food intake

Answer 346

- No NPY or Agrp mutation associated with appetite discovered in humans - POMC deficiency and MC4-R mutations cause morbind obesity - Mutations are not responsible for the prevalence of obesity but is usefule to explain signalling

Answer 347

- Higher centres - Amygdala - emotion, memory - Other parts of hypothalamus e.g. lateral hypothalamus - Vagus to brainstem to hypothalamus

Answer 348

- Circulating hormone produced by adipocytes in white adipose tissue - Leptin - Hypothalamus senses the concentration of hormone in the plasma - Then alters neuropeptides to increase or decrease food intake (and regulates thermogenesis) - The ob/ob mouse lacks leptin (obese), and when replaced it decreases its weight - More fat = more leptin

Answer 349

- Absent leptin -> increased food intake, decreased energy expenditure and decreased fat and glucose metabolism - Regulatory defect -> and increase in adipose still releases normal leptin levels - Leptin resistance -> high leptin levels with no effects

Answer 350

- Small number of cases identified (RARE) - Mutation in ob gene (homologous to ob/ob mouse) - Severely hyperphagic and obese - When leptin is replaced their weight decreases

Answer 351

- Ghrelin - stimulated hunger | - Peptide YY3-36 - inhibits hunger

Answer 352

- 36 amino acids long but truncated (34 amino acids long) in PYY3-36 - Post-prandial secretion of PYY increases with increasing meal size/calorie intake - Direcly modulates neurons in the arcuate nucleus: - Inhibits neuropeptide Y release (less stimulation) - Stimulates POMS neurons (more inhibition) - therefore it decreases appetite - Studies show that PYY makes people eat less and feel less hungry

Answer 353

- Peptide, with fatty acid attached to serine (3rd amino acid). Fatty acid necessary to bind to receptor, and possibly helps it to access parts of the brain more easily - Ghrelin release is highest before a meal, then it drops - Causes increased hungriness by: - Stimulating neuropeptide/Argp neurons - Inhibiting POMC neurons - Thereby increasing appetite - Studies show ghrelin increases amount of food eaten and hunger

Alimentary system Flashcards

(379 cards)