GI Flashcards

Question

List the risk factors for gallstones

Answer 1

5 F’s: fat, forty, female, fertile, fair Age Family history Caucasian Low fibre diet Inflammatory bowel disease

Answer 2

↑ secretion of enzyme-rich fluid from pancreas, contraction of gallbladder and relaxation of sphincter of Oddi, ↓ gastric emptying, trophic effect on pancreatic acinar cells, induces satiety

Answer 3

↑ acid secretion by gastric parietal cells, pepsinogen and IF secretion, ↑ gastric motility, stimulates parietal cell maturation

Answer 4

↑ secretion of bicarbonate-rich fluid from pancreas and hepatic duct cells, ↓ gastric acid secretion, trophic effect on pancreatic acinar cells

Answer 5

villous atrophy crypt hyperplasia increase in intraepithelial lymphocytes lamina propria infiltration with lymphocytes

Answer 6

Gastric parietal cells produce intrinsic factor. This binds to vitamin B12 enabling it to be absorbed by the small intestine.

Answer 7

Foregut - stomach, spleen, liver, esophagus, and also parts of the pancreas and duodenum

Answer 8

midgut – which spans from the major duodenal papilla (of the duodenum) to the proximal 2/3 of the transverse colon.

Answer 9

Hindgut - i.e. distal 1/3 transverse colon, descending colon and sigmoid colon

Answer 10

Gilbert’s syndrome is a condition that causes hepatic jaundice due to a genetic defect in uridine diphosphate glucuronosyltransferase (UGT) This genetic defect affects chromosome 2, specifically the locus coding for the UGT-1A1 protein This condition tends to be exacerbated by stress, fasting and acute illness Confirm diagnosis by measuring unconjugated bilirubin Stool and urine will be normal as this condition is characterised by unconjugated hyperbilirubinaemia

Answer 11

Most circulating proteins are synthesised by the liver and are used as a synthetic measure of liver function The liver synthesises albumin, the most abundant plasma protein, as well as other glycoproteins due to its role in glycation of proteins Also synthesises other transport and binding proteins e.g. transferrin, apoferritin

Answer 12

Causes of hepatitis Alcohol Viral Autoimmune Drugs Metabolic disease Biliary disease Drugs or toxins Cryptogenic Alcohol or metabolic Biliary disease Idiopathic Haemochromatosi

Answer 13

Liver failure Portal hypertension Hepatocellular cancer

Answer 14

Reduced albumin and other transport proteins Reduced intermediary metabolism Impaired synthesis of urea and glycogen (higher risk of hypoglycaemia) Coagulopathy Failure in the synthesis of clotting factors Immunodeficiency Lack of production of complement Jaundice Altered xenobiotic metabolism (reduced first-pass effect) Circulatory and endocrine disturbances

Answer 15

Cirrhosis increases resistance to blood flow through the liver Increases pressure in portal circulation causing: Portal-systemic shunts and varices There is a junction where the portal and systemic circulation meet If pressure is high, portal circulation blood can go to systemic circulation Examples Gastroesophageal junction Left gastric vein and tributaries to azygos vein Anterior abdominal wall Superficial veins of abdominal wall and paraumbilical veins (caput medusae) Anus Superior, middle and inferior rectal veins Varices (vein enlargement) may rupture leading to massive haematemesis and precipitate hepatic failure & encephalopathy Ascites Increased fluid in abdominal cavity Splenomegaly Backpressure is exerted on spleen through portal circulation Spleen is distensible so can accumulate more blood and become distended More vulnerable to trauma Consumption of platelets

Answer 16

Classical lobules 1-2mm hexagonal lobules centred on the terminal hepatic venule Portal lobules Triangular area formed by 3 central veins Liver acinus Ovoid area of liver tissue centred on the sides of the classical lobule between 2 central veins

Answer 17

Zone 1 - periportal Closest to afferent arteriole, higher oxygen concentrations Functions Gluconeogenesis Cholesterol synthesis Oxidative energy metabolism e.g. TCA cycle Amino acid utilisation Bile acid synthesis Urea synthesis Hepatocytes actively synthesise plasma proteins and glycogen Zone 2 - intermediate Zone 3 - perivenular Closes to terminal hepatic venule, low oxygen concentration Susceptible to hypoxia Alcoholic liver disease usually starts here Functions Xenobiotic metabolism Glycolysis Lipogenesis Ketogenesis Glutamine synthesis

Answer 18

Non-volatile and hydrophobic substances are made more hydrophilic by reactions in the liver to promote excretion in the urine or bile Phase 1 reactions Suitable when a polar group is available Involve hydrolysis, oxidation and reduction Occur in smooth endoplasmic reticulum utilising cytochrome P450 enzymes These enzymes add an oxygen group to drug side-chains to make a reactive site Produce hydroxylated or carboxylated compounds Molecules produced are generally more reactive Sometimes toxic or pharmacologically active molecules are produced Precursor to phase 2 reactions Phase 2 reactions Subsequent conjugation with glucuronic acid, methyl/acetyl radicals, glycine/taurine or sulphate. Tends to increase water solubility and potential for active transport to promote excretion

Answer 19

Stores carbohydrates as glycogen, releasing them during glycogenolysis Carries out gluconeogenesis (synthesis of glucose from other sources such as lactate or pyruvate) Utilises glucose as an energy substrate for glycolysis, TCA cycle Converts fructose and galactose into glucose phosphate

Answer 20

The liver synthesises cholesterol, fatty acids, triglycerides, phospholipids and lipoproteins The liver carries out mitochondrial beta-oxidation of short-chain fatty acids

Answer 21

The liver performs deamination, removing an amino group from amino acids to form ammonia, while the carbon backbone is regenerated into glucose, fatty acids or Krebs cycle intermediates Cells remove ammonia by converting it into urea, which is excreted by the kidneys The liver performs transamination, transferring an amino group from an amino acid to a ketoacid and vice versa, producing a new amino acid and a new ketoacid

Answer 22

Bile produced by hepatocytes drains into bile canaliculi Bile canaliculi consist of the walls of two hepatocytes joined by tight junctions Bile canaliculi drain into ducts (junction between these is known as the Canal of Hering) > Interlobular ducts Septal ducts Intrahepatic ducts Left and right hepatic ducts Left hepatic duct drains left functional lobe Right hepatic duct drains right functional lobe Caudate lobe drained by both Left and right hepatic ducts merge to form the common hepatic duct The common hepatic duct merges with the cystic duct (drains the gallbladder) to form the common bile duct The common bile duct merges with the pancreatic duct to form the hepatopancreatic ampulla of Vater Enters the descending part of the duodenum via the greater duodenal papilla (controlled by the sphincter of Oddi)

Answer 23

End-stage liver disease; a diffuse process (affecting the whole liver) characterised by nodule formation (micro or macronodular) and fibrosis. Colour change (green) may result due to increased bile retention by liver and impaired secretory function Cirrhosis is the result of chronic inflammation lasting for years due to persistence of the injury-causing agent Hepatocyte injury leads to progressive liver cell loss Fibrous scarring occurs, as well as hepatocyte regeneration, but hepatocytes may form hyperplastic nodules Architecture becomes abnormal, pressing on portal tract, biliary and vascular structures, leading to ischaemia Ischaemia worsens liver damage

Answer 24

Congenital enzyme deficiency Nutritional deficiency/excess of substrate Toxic/chemical damage to organelles Hypoxic/ischaemic insult Secondary to metabolic effects of disease Inherited disease

Answer 25

Caused by H. Pylori infection H. pylori produces urease, which converts urea and water into ammonium bicarbonate (dissociates into ammonia and carbon dioxide) Ammonia is alkaline and allows the bacterium to survive in conditions of low pH It disturbs the negative feedback mechanisms involving D cells, as they sense high pH levels, they do not secrete somatostatin to reduce gastric acid secretion G cells continue to produce gastrin to stimulate acid secretion Highly acidic secretions reach the duodenum causing ulceration Duodenal ulcers are improved by milk/meals while gastric ulcers are worsened after a meal

Answer 26

Hepatocytes Kupffer cells Endothelial cells Perisinusoidal (fat-storing) cells Liver-associated lymphocytes

Answer 27

Bile salts Conjugated bilirubin Water Electrolytes Mucin Bicarbonate Cholesterol Phospholipids

Answer 28

Conjugated bilirubin enters the duodenum and is converted into unconjugated bilirubin by beta-glucuronidase Unconjugated bilirubin is acted upon by intestinal anaerobes, forming urobilinogen Urobilinogen is mostly reabsorbed and returns to the liver via the enterohepatic circulation Some urobilinogen is filtered by the kidneys and excreted in the urine Urobilinogen which reaches the colon is converted to stercobilin, which is excreted in the faeces, giving them a brown colour

Answer 29

Hepatic recesses form an extension of the peritoneal cavity They form a potential space containing a small amount of fluid to allow smooth movement of internal organs Subphrenic recess Between superior anterior portions of liver and diaphragm Separated into right and left by falciform ligament Hepatorenal recess Between right kidney and right suprarenal gland Continuous with right subphrenic space anteriorly Clinical importance: Common site for abscesses Pus can cause peritonitis

Answer 30

Bleeding Due to drugs e.g. iron medication, gold, caffeine, cocaine Can result in vomiting of blood (haematemesis) or passage of altered black blood to the rectum (melena) Can lead to anaemia Can erode an unusually large blood vessel (Dieulafoy’s lesion) Perforation Gastric or duodenal ulcer erodes through wall connecting peritoneal cavity with inner gastric lining Presents acutely with severe abdominal pain

Answer 31

A hiatus hernia describes the protrusion of the stomach through the diaphragmatic hiatus from the abdominal cavity into the thoracic cavity Results in a separation of the lower oesophageal sphincter from the phrenoesophageal ligament of the diaphragmatic crura Predisposing factors which may weaken the phrenoesophageal ligament include obesity, pregnancy and age The lack of separation between 2 high pressure zones leads to acid reflux Diagnosis: High resolution manometry Endoscopy Barium studies

Answer 32

Hydrochloric acid Mucin Pepsin Intrinsic factor

Answer 33

Regurgitation of food and fluid Heartburn Complications - Columnar metaplasia Barret’s oesophagus - risk of oesophageal adenocarcinoma Benign stricture formation Scarring causes oesophageal narrowing, leading to dysphagia Treated through balloon dilation during endoscopy Reflux oesophagitis Ulceration Can lead to bleeding/iron deficiency anaemia

Answer 34

Mouth: Small amounts of lingual lipase Breaks down triglycerides into monoacylglycerols, diacylglycerols and fatty acids Stomach: Small amounts of gastric lipase Duodenum: Pancreatic lipase and co-lipase Bile acids for emulsification of lipids & formation of micelles Fatty acids diffuse to apical membrane in micelles, entering enterocyte Short-chain fatty acids move directly into blood circulation Long-chain fatty acids are packaged into chylomicrons and exit via basolateral membrane to enter lacteals Eventually drain into blood circulation via thoracic duct

Answer 35

Glucose and galactose are taken up by enterocytes via a sodium-glucose co-transporter (SGLT1) Sodium is exchanged for potassium to maintain the electrochemical gradient Fructose enters enterocytes via facilitated diffusion through a GLUT5 transporter All 3 pass into the bloodstream by a GLUT2 transporter

Answer 36

The luminal plasma membrane contains sodium-dependent amino acid transporters Amino acids are absorbed and enter the bloodstream via facilitated diffusion (selective uniporters) Dipeptides and tripeptides are taken up by enterocytes via co-transport with hydrogen ions to undergo further breakdown, eventually entering the bloodstream as amino acids

Answer 37

Antacids: Weak alkalis which neutralise acid and relieve symptoms of heartburn Usually sodium hydroxide combined with a metal salt e.g. magnesium/aluminium hydroxide Alginates: Promote mucosal resistance In presence of acid, form a gel-like raft which adheres to the top of the acid pocket in the proximal stomach Release of CO2 makes gel float to proximal stomach and prevents acid reflux

Answer 38

Acid suppressants which reversibly and competitively bind to the H2 receptor on parietal cells and prevent binding of histamine secreted by ECL cells Reduced stimulation of parietal cells leads to reduced gastric acid secretion Usually heals peptic ulcers but lower success rate with erosive oesophagitis Examples Cimetidine (Tagamet) Ranitidine (Zantac) Famotidine (Pepcid)

Answer 39

Acid suppressants which irreversibly bind to the H+/K+ pump on parietal cells, leading to reduced gastric acid secretion Heals oesophagitis and peptic ulcers Examples Omeprazole (& esomeprazole) Lansoprazole Pantoprazole

Answer 40

Reduced micronutrient absorption (iron, calcium, vitamin B12) Reduction in gastric acid output Reduced gastric antimicrobial function Increase in serum gastrin levels Leads to hyperplastic mucosa in stomach Fundic gland polyps can be found due to ECL cell hyperplasia Rebound acid hypersecretion after discontinuation Idiosyncratic Diarrhoea due to lymphocytic colitis Hypomagnesaemia (long-term) Interstitial nephritis (rare) Interaction w/ metabolism of other drugs

Answer 41

Total: 4g Daily need: 1-2mg/d

Answer 42

Stored in 2 forms Ferritin Soluble, predominantly intracellular Iron safe and readily available from reticuloendothelial system (RES) Ferritin is an acute phase protein (can be increased due to tissue inflammation) Haemosiderin Insoluble conglomerates of ferritin Iron slowly available

Answer 43

Haem iron: red meat Easily absorbed Non-haem iron: vegetables, white meat Must be reduced from ferric (Fe3+) to ferrous (Fe2+) form by duodenal cytochrome b1 in the presence of vitamin C (vitamin C ferrireductase) Iron is mainly absorbed in the duodenum & taken up by enterocytes via the divalent metal transporter (DMT1) Iron is exported via the transmembrane protein ferroportin Hepcidin degrades ferroportin The interaction between hepcidin and ferroportin regulates GI iron absorption

Answer 44

Autosomal recessive disorder leading to iron overload as a result of abnormalities in HFE gene which regulates hepcidin Homozygous for C282Y mutation or compound heterozygous (C282Y/H63D - less severe phenotype) Males more at risk, females protected by menstruation and childbirth Results in 100% transferrin saturation, so increased risk of metabolically active non-transferrin-bound iron Can lead to tissue damage and lipid peroxidation

Answer 45

Symptoms - Pancreas: diabetes Heart: restrictive cardiomyopathy Skin: bronzing (iron stimulates melanin production) Liver: damage and cirrhosis Joints: arthritis (affects 2nd and 3rd MPJ in hand) Treatment Venesection: take blood weekly until ferritin and transferrin saturation decrease

Answer 46

Causes: Iron deficiency anaemia (IDA) in males and post-menopausal women is due to GI blood loss until proven otherwise In young women it is usually due to menstruation/pregnancy Exception: coeliac disease (iron malabsorption) Presents with decreased transferrin saturation Red blood cells are microcytic and hypochromic (small and light in colour)

Answer 47

Gluten is digested by intestinal proteases but high proline content makes this difficult; undigested peptides appear These need to be deamidated by tissue transglutamase (TTG) and presented to antigen-presenting cells (APCs) in intestinal mucosa If the individual has HLA DQ2/8 APCs (genetically predisposed) presenting gluten peptides to CD4+ T cells, these will activate T cells and B cells to produce anti-gliadin antibodies Cytokine cascade is initiated (interferon, interleukins…) which drives the inflammatory process

Answer 48

Osteoporosis Dermatitis herpetiformis IgA deficiency Functional hyposplenism Increased risk of cancer (especially T cell lymphoma and small bowel adenocarcinoma) Increased overall mortality (secondary to increased autoimmune diseases)

Answer 49

Increased water movement into gut, stops when patient fasts 2 causes Non-absorbable solutes Laxatives, antacids Acarbose Orlistat - Failure to digest or absorb nutrients Digestive enzyme deficiencies Pancreatic insufficiency Loss of enterocytes Bacterial overgrowth Lymphatic obstruction Diabetes mellitus Short bowel syndrome

Answer 50

Caused by acute infections; enterotoxins stimulate colonic enterocyte secretion (does not stop when patient is fasting) - Bacteria Vibrio cholerae Campylobacter Escherichia coli Salmonella Shigella - Viruses Norovirus Rotavirus Coronaviruses Sapovirus Adenoviruses Protozoa Cryptosporidium Giardia - Some endocrine syndromes Carcinoid syndrome (secretes hormones e.g. VIP) Zollinger-Ellison syndrome Drugs Some asthma medications, antidepressants, some cardiac drugs Certain metals, organic toxins, plant products (arsenic, insecticides, mushroom toxins)

Answer 51

Damage to intestinal transport system due to ongoing inflammation - destruction of the epithelium results in exudation of serum and blood into lumen and impairs absorption Inflammatory bowel disease - Crohn’s disease, ulcerative colitis Irritable colon Infectious disease Shigella, salmonella Types: - Acute watery diarrhoea - dehydration e.g. E. coli, V. cholerae, rotavirus Bloody diarrhoea - dysentery, intestinal damage, nutrient loss e.g. Shigella Persistent diarrhoea - >14 days, undernourished children, concomitant disease

Answer 52

Chymotrypsin acts on peptides where the carboxyl group is provided by tyrosine and phenylalanine (uncharged forms, aromatic amino acids) Trypsin acts on peptides with lysine and arginine on C-terminal side (but not if there is a proline on the carboxyl side)

Answer 53

Lymphatic vessels drain into pre-aortic lymph nodes, which surround arteries Coeliac nodes surround coeliac trunk > collect lymph from organs derived from foregut Superior mesenteric nodes surround SMA > drain organs derived from midgut Inferior mesenteric nodes surround IMA (hindgut) Drainage of lymph: inferior > superior > coeliac Coeliac nodes drain into cisterna chyli > thoracic duct > bloodstream