GastroIntestinal Flashcards

Question

LO 4.6 Describe the function of the stomach defences

Answer 1

The luminal pH of the stomach is usually below 2. Without any protection, this would dissolve mucosa. Neck cells secrete mucus to protect the mucosa. Mucus Mucus is Sticky, so is not easily removed from the stomach lining. It is also Basic, due to Amine groups on the proteins. The mucus forms a ‘unstirred layer’ that ions cannot move through easily. H+ ions slowly diffuse in and react with the basic groups on mucus and with HCO3- that is secreted by surface epithelial cells. Because of the unstirred layer, HCO3- stays close to the surface cells. This means the pH at the surface cells is well above 6. Mucus and HCO3- secretion from neck cells and surface cells respectively is stimulated by prostaglandins, which are promoted by most factors that stimulate acid secretion. Breaching the Stomach’s Defences o Alcohol  Dissolves the mucus, allowing the acid to attack the stomach o H. Pylori  Surface cells become infected, inhibiting mucus/HCO3- production o NSAIDS  Inhibit prostaglandins, therefore reducing defences  Some, like aspirin are converted to a non-ionised form by stomach acid, allowing them to pass through the mucus layer into cells before they re-ionise. If the stomach’s defences are breached it results in peptic ulcers. Treatment involves reducing acid secretion (see above) and, if present, eliminating H. Pylori with antibiotics.

Answer 2

Receptive Relaxation As food travels down the oesophagus, a neural reflex carried out by the vagus nerve triggers the relaxation of the muscle in the stomach’s wall, so pressure does not increase. This means that pressure in the stomach does not increase as it fills limiting reflux and allowing us to consume large meals (but not if there is damage to the vagus nerve). Rhythmic Contractions The stomach has longitudinal and circular muscle that is driven by a pacemaker in the cardiac region. The pacemaker fires ~3 times a minute, causing regular, accelerating peristaltic contractions from the Cardia  Pylorus. This, combined with the stomach’s funnel shape both mixes the contents of the stomach and moves liquid chyme into the pyloric region. This occurs as the accelerating peristaltic wave overtakes larger lumps, driving them back into the fundus. Chyme however is decanted into the pyloric region.

Answer 3

The accelerating, rhythmic, peristaltic contraction moves solid lumps backwards into the fundus of the stomach whilst letting liquid chyme move forwards. As the chyme enters the pyloric region, a small squirt is ejected before the peristaltic wave reaches the pylorus and shuts it, so the rest of the chyme returns to the stomach. Control of Gastric Emptying o Three peristaltic waves  three ejected squirts of chyme a minute. o Squirt volume affected by the rate of acceleration of peristaltic wave and hormones from the intestine. o Gastric Emptying is slowed by fat, low pH and Hypertonicity in the duodenum.

Answer 4

Gastro-oesophageal reflux disease (GORD): There are anti-reflux mechanisms that prevent reflux of gastric into the lower oesophagus: o Lower oesophageal sphincter – which is usually closed and transiently relaxes as part of physiology of swallowing to allow bolus to move into stomach o Oesophagus enters stomach in abdominal cavity o Pressure in abdominal cavity is higher than that of thoracic o Right crus of diaphragm acts as sling around the lower oesophagus Some acid reflux is normal and this is normally dealt with by secondary peristaltic waves, gravity and salivary bicarbonate. Clinical features of GORD occur when antireflux mechanisms fail and there is prolonged contact of gastric juices with lower oesophageal mucosa. Clinical features o Dyspepsia (heartburn)  Worse on lying down, bending over and drinking hot drinks. Investigations and diagnosis o Usually clinical diagnosis made without investigation on symptoms alone, no need to investigate unless alarming symptoms (such as dysphagia) or hiatus hernia is suspected (which would be investigated by endoscopy) Management o Lifestyle  Lose weight, stop smoking, reduce alcohol consumption, reduce consumption of food groups known to aggravate (e.g. chocolate, fatty foods) o Medication  Simple antacids – e.g. calcium carbonate (neutralisies acid)  Raft antacids (alginates) – e.g. Gaviscon liquid, taken after eating which creates protective raft that sits on top of stomach contents to prevent reflux  PPIs – e.g. omeprazole – reduction in acid secretion by parietal cells  H2 antagonists – e.g. ranitidine – blocks H2 receptors which reduced acid secretion Complications Continual contact of gastric juices with oesophageal mucosa can lead to metaplastic change  Barrett’s oesophagus

Answer 5

Peptic ulcer disease (PUD): Peptic ulcer is break in superficial epithelial cells penetrating down into Muscularis mucosa of either stomach (GU) or duodenum (DU). Most DUs are found in duodenal cap and GUs are most commonly seen in lesser curvature of stomach Causes Leading cause in developed world is use of NSAIDs, which inhibit production of prostaglandins, prevents production of protective unstirred layer (innate protection against gastric acid). 50% of patients taking long term NSAIDs have mucosal damage and 30% when endoscoped have peptic ulceration but only 5% will be symptomatic and only 1-2% will have complication such as GI bleed. Epidemiology Duodenal Ulcers found in ~10% adult population and are 2-3 times more common than GUs. Prevalence is falling for younger people (especially men) and increasing in older people (especially older women). In developed countries increased prevalence of NSAID-associated DUs and decreasing prevalence of H pylori associated ulceration Clinical features o Recurrent, burning epigastric pain (pain is often worse at night and when hungry with Duodenal Ulcers and relieved when eating). Pain may subside with antacids  Persistent, severe pain suggest penetration of ulcer into other organs  Back pain suggest penetrating posterior ulcer o Can also get nausea, vomiting (though less common) o With GUs can get weight loss and anorexia o May be asymptomatic and present for first time with hematemesis when ulcer has perforated blood vessel(s) Investigations o Investigate H pylori infection o In older patients (over 55y/o) or with other alarming symptoms  endoscopy to exclude cancer Management o If due to H pylori infection  Triple Therapy  Proton Pump Inhibitor – Omeprazole  Antibiotics – Clarithromycin / Amoxicillin  H2 Antagonist – Cimetidine o If taking NSAIDs – stop or review – use alternatives (NSAIDs with lower risk of causing PUD), or use prophylactic PPI as well as NSAID  PPI – e.g. omeprazole Complications of PUD o Haemorrhage of blood vessel which ulcer has eroded  presents with hematemesis and melena o Perforation of the ulcer – more common in DUs than GUs – usually perforate into peritoneal cavity o Gastric outlet obstruction  can be pre-pyloric, pyloric or duodenal. Occurs either because of active ulcer with oedema or due to healing of an ulcer with associated fibrosis (scarring). Gastric outlet obstruction normally presents as vomiting without pain.

Answer 6

Helicobacter pylori infection o H pylori is a gram negative, aerobic, helical, urease producing bacterium that resides in the stomach of infected individuals. o Production of urease produces ammonia, which neutralises acidic environment, which allows bacterium to survive. o It colonises gastric epithelium – in mucous layer or just beneath. Damage to epithelia occurs through enzymes released and through induction of apoptosis. Damage also occurs due to the inflammatory response to the infection (inflammatory cells and mediators) Diagnosis o IgG detected in serum (relatively good sensitivity and specificity) o 13C-urea breath test (13C-urea ingested – if H pylori present the urease produced will break down 13C-urea to NH3 and CO2 – CO2 (where the carbon is 13C) will be exhaled on breath and detected). o Can also take gastric sample by endoscopy and detect by histology and culture Treatment o Triple therapy.  Proton Pump Inhibitor – Omeprazole  Two Antibiotics – Clarithromycin / Amoxicillin  H2 Antagonist (if severe) o This standard eradication therapy, depending on local resistance, is successful at eradicating infection in 90% of patients.  7-14 day treatment – 14 days more effective but side-effects of treatment may put patients off finishing two week course H pylori causing gastric disease: o Gastritis  Usual effect of infection, which is usually asymptomatic.  Chronic gastritis causes hypergastrinaemia due to gastrin release from astral G cells  this increased acid production is usually asymptomatic but can lead to duodenal ulceration (which will eventually produce symptoms) o Peptic ulcer disease  Duodenal ulcers (DUs)  prevalence of DU due to H pylori is falling due to decreased prevalence of H pylori infection. If ulcers due to H pylori infection, eradication of infection relieves symptoms and decreases chances of recurrence. The precise mechanism of ulceration is unclear (only occurs in 15% of infected people)  factors implicated though are genetic predispositions, bacterial virulence, increased gastrin secretion and smoking  Gastric ulcers (GUs)  associated with gastritis affecting the body as well as antrum, which can cause parietal cell loss  reduction in acid production. Ulceration thought to occur due to reduction in gastric mucosal resistance due to cytokine production as a result of infection o Gastric cancer

Answer 7

If due to H pylori infection  Triple Therapy  Proton Pump Inhibitor – Omeprazole  Two Antibiotics – Clarithromycin / Amoxicillin  H2 Antagonist (if severe) If taking NSAIDs – stop or review – use alternatives (NSAIDs with lower risk of causing PUD), or use prophylactic PPI as well as NSAID  PPI – e.g. omeprazole

Answer 8

Acid secretion may be reduced by inhibition of: Histamine at H2 Receptors o E.g. Cimetidine o Removes the amplification of Gastrin/Ach signal Proton Pump Inhibitors (PPIs) o E.g. Omeprazole o Prevents H+ ions being pumped into parietal cell canaliculi

Answer 9

Chyme – The stomach empties chyme into the duodenum that is: o Acidic  Corrected by HCO3- secreted from the pancreas, liver and duodenal mucosa  HCO3- produced during the production of Gastric Acid o Hypertonic  Corrected by the osmotic movement of water into the duodenum across its wall o Partly digested  Digestion completed by enzymes from the pancreas and duodenal mucosa, with bile acids from the liver.

Answer 10

Bile – Made up of two components, Bile Acid Dependent and Bile Acid Independent. ``` Bile Acid Dependent Secreted by cells lining the canaliculi Bile acids (salts) Cholic Acid/Chenodeoxycholic Acid Bile salts are conjugated to Amino Acids, travelling as micelles in bile. They play a major role in the digestion and absorption of fat. Cholesterol Bile pigments (majority is Bilirubin) ``` ``` Bile Acid Independent Secreted by cells lining the intra-hepatic bile ducts Alkaline juice (HCO3-) like that from pancreatic duct cells ```

Answer 11

The microscopic structure of the liver supports its function. The basic functional unit is a lobule surrounding a central vein, which drains blood from the liver to the systemic veins. Blood from the hepatic portal vein and hepatic arteries enters vessels at the periphery of the lobule, and flows through sinusoids lined by hepatocytes to the central vein. Hepatocytes are very complex cells that support most of liver functions. Bile is formed in canaliculi, and flows towards the periphery into bile ducts.

Answer 12

In response to Gastric emptying, the duodenum secretes Cholecystokinin (CCK). This stimulates the contraction of the Gall Bladder, ejecting concentrated bile acids together with enzymes from the pancreas. Alkali from the Pancreas and Liver is also released in response to Secretin. Bile acids are released through the Ampulla of Vater, and aid with the digestion and absorption of fats. They continue to the terminal ileum, where they are actively absorbed by the epithelium. The venous return from the gut enters the hepatic portal blood, where hepatocytes actively take up Bile Acids and re-secrete them into Canaliculi. Most bile acids are recovered, but some are unconjugated by the action of gut bacteria and are lost. Hepatocytes subsequently replace it.

Answer 13

Bile acids return to the liver in between meals and are secreted by canaliculi cell walls a long time before they are next needed. Until they are needed, they are stored in the gall bladder. To reduce the volume that needs to be stored, bile acids are concentrated by the transport of salt and water across the gall bladder epithelium. However, the concentration process increases the risks of precipitation, leading to Gall Stones. Gallstones are often asymptomatic, but they can move into the neck of the gall bladder or biliary tree, causing very painful biliary colic or even obstruction. This is often followed by inflammation (Cholecystitis) and infection of the Gall Bladder. Pain from Gallstones can be worse after eating, as the secretion of Cholecystokinin (CCK) will cause the gall bladder to contract.

Answer 14

``` The exocrine pancreas secretes alkaline juice (HCO3-) and enzymes: o Proteases  Trypsin (ogen)  Chymotrypsin  Elastase  Carboxypeptidase o Amylases o Lipases ```

Answer 15

The exocrine pancreas is a gland with Acini and Ducts. o Acini  Secrete Enzymes, mostly as inactive precursors  Packaged into condensing vacuoles, forming Zymogen granules  Zymogen granule secreted by exocytosis  Activated in the intestine by enzymatic cleavage o Ducts  Secrete Alkaline Juice (HCO3-)

Answer 16

HCO3- is present in the blood at elevated concentrations due to gastric acid secretion. The pancreatic duct cells secrete the HCO3- using the same cellular mechanism as other HCO3- secreting cells: o Na-K-ATPase sets up a Na+ concentration gradient o Hydrogen ions are exported from the duct cell into ECF using the Na+ concentration gradient o H+ ions combine with HCO3- to form H2O and CO2, which are taken up into the cell o H2O and CO2 reform H+ and HCO3- inside the cell o HCO3- is exported into the duct lumen o H+ ion is recycled, ‘going around in a circle’ to carry more HCO3- from the ECF to the Lumen Duct secretion is stimulated by Secretin, which is released from Jejunal cells in response to low pH. Cholecystokinin (CCK) facilitates secretin’s action.

Answer 17

``` Pancreatic Secretions o Acinar  Stimulated by Cholecystokinin (CCK)  Released from duodenal APUD cells  Stimulated by Hypertonicity and Fats o Duct  Stimulated from Secretin  Released from jejunal cells  Stimulated in response to low pH ``` Biliary Secretion o Cholecystokinin secreted by the duodenum in response to gastric emptying o Stimulates contraction of gall bladder muscle

Answer 18

Fats are relatively insoluble in water, making them tend to aggregate into large globules, preventing the effective action of digestive enzymes. Acid in the stomach exacerbates this. In the duodenum, bile acids enable fats to be incorporated into small (4-6nm) micelles, with fats in the middle and the polar components of bile acids on the outside. These micelles generate a high surface area for the action of lipases, which cleave the fatty acids from glycerol. The micelles also carry these products into the ‘unstirred layer’ immediately next to the mucosa, where fatty acids can be released to slowly diffuse into the epithelial cells. Once inside the epithelial cells they are reconstituted into triacylglycerols and re-expelled as chylomicrons, structured small particles made up of lipids covered in phospholipids, which facilitate the transport of fat in the lymphatic system from the gut to systemic veins. Steatorrhoea If bile acids or pancreatic enzymes are not secreted in adequate amounts, fat appears in faeces. This makes them pale, float and smell foul. This is relatively common, and is called Steatorrhoea, or ‘Fatty Faeces’. Jaundice Bile pigments are excretory products. The most common bile pigment is Bilirubin, produced as a product of haemoglobin breakdown. Bilirubin is conjugated in the liver and secreted in the bile to be excreted in faces. If it cannot be excreted it accumulates in the blood, giving the condition known as Jaundice.

Answer 19

``` Inevitably, when we ingest food and water we also risk ingesting toxins. These include: o Chemical o Bacteria o Viruses o Protozoa o Nematodes (Roundworms) o Cestodes (Tapeworms) o Trematodes (Flukes) ```

Answer 20

Defences can be split into two categories, Innate (Physical and cellular) and Adaptive. Physical Innate Defences o Sight / Smell  If food looks or smells bad you don’t eat it o Memory  If food tastes bad, you don’t eat it next time o Saliva  pH 7.0  Contains lysozyme, lactoperoxidase, complement, IgA and polymorphs  Washes toxins down into the stomach o Stomach Acid  Low pH kills the majority of bacteria and viruses o Small Intestine Secretions  Bile  Proteolytic enzymes  Lack of nutrients  Shedding of epithelial cells o Colonic mucus  Protects the colonic epithelium from it’s contents o Anaerobic environment (Small bowel, colon) o Peristalsis/Segmentation  Normal intestinal transit time is 12 – 18hrs. If peristalsis is slowed, gut infections are prolonged. E.g. shigellosis. ``` Cellular Innate Defences o Neutrophils o Macrophages  Kupffer cells in the Liver o Natural Killer cells (Kill virus infected cells) o Tissue Mast Cells o Eosinophils  Parasitic infections ``` Hepatic Portal System o All venous blood from the GI tract passes through the liver before returning to systemic circulation o Kupffer cells are specialised macrophages in the liver Adaptive Defences (Cellular) o B Lymphocytes o Produce antibodies including IgA and IgE that are particularly effective against extracellular microbes o T Lymphocytes o Directed against intracellular organisms o Lymphatic Tissues o Mucosal Associated Lymphoid Tissue (MALT) in the GI tract is called Gut Associated Lymphoid Tissue (GALT) o GALT is diffusely distributed by also nodular in three locations:  Tonsils  Peyer’s patches  Appendix

Answer 21

Saliva Severe illness and/or dehydration results in reduced salivary flow (Xerostomia), which then leads to microbial overgrowth in the mouth and dental caries. This can lead to parotitis (salivery gland infections) caused by Staphylococcus aureus. Gastric Acid Reduced/Absent Production Patients who have absent or low Gastric Acid production (Achlorhydria), e.g. pernicious anaemia, drugs such as H2 Antagonists, PPIs) are more susceptible to Shigellosis, Cholera and Salmonella infections. In a hospital environment, patients taking protein pump inhibitors are at increased risk of acquiring Clostridium difficile. Resistant Organisms o Mycobacterium Tuberculosis is resistant to gastric acid (Acid and Alcohol fast bacterium) o Enteroviruses, such as Hepatitis A, Polio and Coxsackie are resistant to gastric acid o Helicobacter Pylori produces urease, which acts on urea to produce a protective cloud of ammonia Mast Cells o Mast cell granules contain Histamine o Gut infections which activate complement recruit mast cells, which then release histamine o This causes vasodilation and increased capillary permeability  Can get massive fluid loss o In cholera, may get losses of 1 Litre/hr  60% Mortality if untreated Gut Associated Lymphoid Tissue (GALT) o Tonsillitis o Ileocaecal lymphatic tissue o Mesenteric adenitis is a common cause of right iliac fossa pain in children, and can easily be mistaken for appendicitis o Caused mostly by adenovirus/coxsackie virus o Typhoid fever causes inflamed Peyer’s patches in terminal ileum, which can perforated and kill patients o Appendicitis  Many cases arise from lymphoid hyperplasia at the appendix base leading to an obstructed outflow o Stasis  Infection  Purulent appendicitis is commoner during epidemics of chickenpox in children  Appendix may be obstructed by a faecolith o Calcified faecal matter, visible on an X-ray  Appendix may be obstructed by a worm Gut Ischaemia The GI tract’s defence mechanisms require the GI tract itself to have an intact blood supply. Intestinal/hepatic ischaemia due to arterial disease, systemic hypotension, or intestinal venous thrombosis can (frequently does) lead to overwhelming sepsis and rapid death (within hours) Liver Failure Liver failure gives an increased susceptibility to infections, toxins, drugs and hormones. There is also increased blood ammonia due to the failure of the urea cycle. Ammonia is produced by colonic bacteria and the deamination of amino acids, and can cause hepatic encephalopathy. ``` Causes of Liver Failure: o Viral hepatitis  Main cause worldwide o Alcohol  Main cause in the UK o Drugs  Paracetamol, halothane o Industrial solvents o Mushroom poisoning ``` Cirrhosis (Hepatic Fibrosis) Hepatic fibrosis leads to portal venous hypertension, leading to porosytemic shunting and therefore toxin shunting. Portosystemic shunting leads to oesophageal varices, haemorrhoids and caput medusa.

Answer 22

Bile Pigments Bile pigments are excretory products. The most common bile pigment is Bilirubin, produced as a product of haemoglobin breakdown. Bilirubin is conjugated in the liver and secreted in the bile to be excreted in faces. If it cannot be excreted it accumulates in the blood, giving the condition known as Jaundice. Hormones The liver breaks down many hormones, notably insulin.

Answer 23

Albumin Albumin is the most abundant plasma protein. Albumin is essential in maintaining the oncotic pressure needed for proper distribution of body fluids. ``` Coagulation Factors The liver produces several coagulation factors: o I – Fibrinogen o II – Prothrombin o V o VII o IX o X o XI As well as Protein C, Protein S and Antithrombin. ``` Thombopoietin A glycoprotein hormone that regulates the production of platelets by bone marrow. Amino Acid Synthesis o Transamination

Answer 24

Hepatocellular Damage If hepatocytes are damaged, their ruptured membranes will allow Aminotransferases into the blood stream. Their presence there is indicative of liver damage (ALT/AST). Cholestasis (Bile ducts) Bilirubin – Unable to excrete bilirubin, plasma concentration rises Alkaline Phosphatase – Enzyme in cells lining the liver’s biliary ducts. Plasma levels rise with an obstruction. ``` Synthetic function Albumin – Levels reduced in chronic liver disease Prothrombin time (Clotting) – Measures the clotting tendency of blood ```

Answer 25

Damaged hepatocytes have a reduced capacity to excrete bilirubin. This leads to bilirubin accumulating in the blood, giving Jaundice. The increased levels of bilirubin (Hyperbilirubinaemia) results in a yellowish pigmentation of the skin, conjunctival membranes over the scleae and other mucus membranes. Jaundice is clinically detectable at >40umol/L (Normal range <22umol/L)

Answer 26

Pre-Hepatic Jaundice Excessive Bilirubin Production, usually due to an increased breakdown of red blood cells (haemolysis) o Liver unable to cope with excess bilirubin ``` Lab Findings: o Unconjugated hyperbilirubinaemia o Reticulocytosis o Anaemia o  LDH o  Haptoglobin ``` ``` Causes: o Inherited  Red Cell Membrane defects  Haemoglobin abnormalities  Metabolic defects o Congenital Hyperbilirubinaemias  Gilbert’s syndrome  10% of the population  Crigler-Najjar syndrome  Rare  Dublin-Johnson syndrome  Rare o Acquired  Immune  Mechanical  E.g. RBC’s running across metal heart valves  Acquired membrane defects  Infections  Drugs  Burns ``` Hepatic Jaundice Reduced capacity of liver cells to secrete conjugated bilirubin into the blood Lab Findings: o Mixed unconjugated and conjugated hyperbilirubinaemia o  Liver enzymes (ALT/AST) o Abnormal Clotting ``` Causes o Congenital  Gilbert’s Syndrome  Crigler-Najjar syndrome o Hepatic Inflammation  Viral (Hepatitis A, B, C and E, Epstein Barr Virus (EBV))  Autoimune hepatitis  Alcohol  Haemochromotosis  Wilson’s disease o Drugs  Paracetamol o Cirrhosis  Alocohol  Chronic hepatitis  Metabolic disorders o Hepatic tumours  Hepatocellular carcinoma  Metastases ``` Post-Hepatic Jaundice Obstruction to drainage of bile, causing a back up of bile acids into the liver. Can be intrahepatic or extrahepatic. The passage of conjugated bilirubin is blocked. ``` Lab Findings o Conjugated hyperbilirubinaemia o Bilirubin in urine (dark) o  Canalicular enzymes (ALP) o -/ liver enzymes (ALT/AST) ``` ``` Causes o Intrahepatic  Hepatitis  Drugs  Cirrhosis  Primary biliary colic o Extrahepatic  Gallstones/Biliary stricture  Carcinoma o Head of pancreas o Ampulla o Bile duct o Porta hepatis lymph nodes o Liver metastases  Pancreatitis  Sclerosing cholangitis ```

Answer 27

Pathology Fatty liver o Alcohol metabolism generates NADH from NAD+   NADH induces fatty acid synthesis   NAD+ results in decrease fatty acid oxidation o Accumulation of fatty acids in the liver  Glycerol  TAGs o TAGs accumulate, giving fatty liver Alcoholic Hepatitis o Inflammation of hepatocytes Cirrhosis Liver cell necrosis followed by nodular regeneration and fibrosis, resulting in increased resistance to blood flow and deranged liver function. ``` Complications o Hepatocellular carcinoma o Liver failure o Wernicke-Korsakoff syndrome o Encephalopathy o Dementia o Epilepsy ```

Answer 28

``` Causes o Alcohol o Wilson’s Disease o 1-antitrypsin deficiency o Biliary cirrhosis o Haemochromotosis o Hepatitis B or C o Autoimmune hepatitis ``` ``` Clinical Features o Liver dysfunction o Jaundice o Anaemia o Bruising o Palmar erythema o Dupuytren’s contracture ``` ``` Investigations o - /  ALT/AST o  ALP o  Bilirubin o  Albumin o Deranged clotting ``` The management of Cirrhosis includes stopping drinking, treating complications and transplantation.

Answer 29

Portal hypertension is defined as portal venous pressure > 20mmHg. It can be caused by o Obstruction of the portal vein  Congenital, thrombosis or extrinsic compression o Obstruction of flow within the liver  Cirrhosis, hepatoportal sclerosis, Schistosomiasis, sarcoidosis) Portal hypertension may lead to: Ascites The high pressure in the portal venous system means blood is backed up into the abdomen. The increase in hydrostatic pressure in the abdomen means less fluid is reabsorbed into blood vessels at the end of capillary beds. If the liver is damaged, reduced oncotic pressure inside the vessels, due to lack of plasma proteins, may also contribute. Splenomegaly – Due to subsequent increased B.P. in the spleen ``` Porto-Systemic Anastomoses There are several anastomoses between the hepatic portal and systemic veins. As such, when the pressure is increased in the portal venous system, blood is backed up through these anastomoses. The increased blood pressure causes the vessels to dilate, protrude into the lumen, rupture/ulcerate and haemorrhage. o Oesophageal varices o Rectal varices o Caput Medusae ``` Portal  Systemic A. Left Gastric  Azygous/Oesophageal Oesophageal Varices B. Superior rectal  Inferior rectal Rectal Varices C. Paraumbilical  Small epigastric of abdominal wall Caput Medusae D. Colic/Splenic/Portal  Retroperitoneal veins of posterior abdominal wall or diaphragm Portal veins here are on the posterior aspects (bare areas) of secondarily retroperitoneal viscera or the liver.

Answer 30

Bile acids return to the liver in between meals and are secreted by canaliculi cell walls a long time before they are next needed. Until they are needed, they are stored in the gall bladder. To reduce the volume that needs to be stored, bile acids are concentrated by the transport of salt and water across the gall bladder epithelium. However, the concentration process increases the risks of precipitation, leading to Gall Stones. Gallstones are often asymptomatic, but they can move into the neck of the gall bladder or biliary tree, causing very painful biliary colic or even obstruction. This is often followed by inflammation (Cholecystitis) and infection of the Gall Bladder. Pain from Gallstones can be worse after eating, as the secretion of Cholecystokinin (CCK) will cause the gall bladder to contract.

Answer 31

Pancreatitis is an inflammatory process, caused by the effects of enzymes released from pancreatic Acini. ``` Acute o Oedema, Haemorrhage, Necrosis o Severe pain, vomiting, dehydration, Shock o  Amylase, Glycaemia, ALP/Bilirubin o  Ca2+ Chronic o Fibrosis, Calcification o Pain, Malabsorption (Steatorrhoea,  albumin, weight loss) o Jaundice ``` ``` Causes of Pacreatitis – GET SMASHED o Gallstones (Block Pancreatic duct/Amuplla of Vater) o Ethanol (Hyper-stimulation of pancreatic secretions) o Trauma o Steroids o Mumps o Autoimmune o Scorpion bite o Hyperlipidaemia o ERCP/Iatrogenic o Drugs ```

Answer 32

90% of pancreatic carcinomas are Ductal Adenocarcinomas, and they account for ~5% of cancer deaths. Clinical Presentation: Initially symptomless, but then lots of symptoms all at the same time: o Obstructive jaundice, pain, vomiting, Malabsorption, diabetes

Answer 33

``` There are approximately 1014 bacteria in the GI Tract, the majority of which are in the colon. This normal flora and has several beneficial roles: o Synthesise and excrete vitamins  Vitamin K, Vitamin B12, Thiamine o Prevent colonisation by pathogens  Space, Bacteriosides o Kill non-indigenous bacteria  Bacteriosides o Stimulate the development of GALT o Stimulate production of natural antibodies ```

Answer 34

o Cocci/Bacilli o Gram Positive/Gram Negative o Aerobic/Anaerobic (Obligate or facultative) o Some bacteria form protective endospores o Bacillus Anthrax o Clostridium Tetani o Bacteria can stick to surfaces using pili and/or slime Anaerobes versus Aerobes Obligate Aerobes must have oxygen. E.g. Pseudomonas and Mycobacterium TB Obligate Anaerobes die in the presence of oxygen. Bacteroides fragilis / Clostridial organisms. But Clostridia form protective spores Facultative Anaerobes prefer oxygen but can live without it. E.g. Gram –‘ve enteric bacteria such as E. coli and Gram +’ve skin-dwellers such as Staphylococcus. ``` Anaerobic Zones in the GI Tract o Parts of the mouth o Tongue, deep in taste buds, biofilm between teeth, gingival crevice areas o Small Bowel o Colon ``` Mouth Bacteria The mouth has many Anaerobic bacteria, therefore can cause very nasty/fatal infections o Streptococci  Streptococcus mutans cause dental caries/gingivitis (dental plaque) o Staphylococci  Staphylococcus aureus can cause Parotitis o Candida  Oral Thrush, caused by Candida Albicans o Lactobacillus o Enterococcus In a malnourished, dehydrated, immunocompromised or systemically unwell patient, these bacteria can cause tissue destruction, known as Noma / Cancrum Oris. Nose Bacteria The nose has Staphylococcus and Streptococcus amongst many others. The nose is one of three sites for MRSA screening swabs (Nose, Throat, Perineum), as these are the three sites where Staphylococci are normally found. ``` Throat Bacteria / Fungi o Strep. Viridans  100% of people  Non-pathogenic throat commensal  During teeth brushing, dental procedures and general anaesthesia may enter the blood stream (Bacteraemia) o Strep. Pyogenes  Tonsillitis (30%, 70% is viral) o Strep. Pneumoniae  Community acquired pneumonia (30%) o Staphylococci  100% of people o Neisseria Meningitidis  100% of people o Haemophilus Influenzea  Community acquired pneumonia (13%) o Lactobacilli  Makes vagina acidic, so Candida Albicans can’t grow (Thrush) o Corynebacterium Diptheriae o Candida Albicans  Oral/vagina thrush ``` ``` Tonsillitis o 70% Viral  Adenovirus, Rhinovirus, Epstein-Barr Virus (EBV) o 30% Bacterial  Step. Pyogenes ``` Stomach o Helicobacter Pylori  At least 50% of the worlds population is infected  Only 10-20% infected develop gastric/duodenal ulcers  Associated with 90% of Duodenal and 70% of Gastric ulcers Colonic More than 100 species regularly exist in the colon of humans, 95-99% of which are anaerobes, particularly Bacteroides and Clostridial species. o Always present in the colon  Bacteroides fragillis  Bacteroides oralis  Bacteroides melaninogenicus  E. Coli – Most common cause of UTI  Enterococcus faecalis – Second most common cause of UTI o Other Colonic Bacilli (Gram –‘ve Enteric Bacilli)  Pseudomonas  Proteus  Klebsiella  Salmonella  Shigella  Vibrio cholera  Campylobacter Although it is only the colon that normally contains large numbers of bacteria, if we are operating on the small bowel it will be abnormal. This all gut surgery is viewed as ‘dirty surgery’ with a high risk of wound infection. To reduce surgical wound infection, antibiotics are given prophylactically. They need to be able to cover Anaerobes, Gram –‘ve Bacilli and Gram +’ve Bacilli. Metronidazole kills anaerobes, so it is given with a broad-spectrum antibiotic such as Gentamicin or Cephalosporin. Faecal Peritonitis Has a high mortality rate, even in young fit people, due to the huge numbers of bacteria floating free in the peritoneum. Perianal Abscess Glands in the anal canal produce mucus for lubrication to aid with passing faeces. Infection of them leads to abscess around the anus – perianal abscess. Vaginal Flora Lactobacillus (Gram +’ve Bacilli) is a normal vaginal flora organism. It converts glycogen into lactic acid, providing an acidic environment to prevent other bacteria and candida albicans from growing (Thrush). Perineal Skin o Bacteroides  Cannot survive O2  Not present o E. Coli  Can survive O2  Present o Enterococcus faecalis  Can survive O2  Present o Lactobacillus  Can survive O2  Present Urinary Tract Infections 90% of UTIs occur in women, as there is a much shorter distance from the anus to the urethra. The commonest causative organism is E. coli, followed by Enterococcus faecalis and thereafter various Gram –‘ve enteric bacilli (Klebsiella, Proteus, Pseudomonas). Clostridia Tetani – Tetanus o Neonatal tetanus kills 60,000 a year Difficile – Pseuomembranous colitis o Severe inflammation of the colon o Often arises after antibiotic treatment o Produces spores, which are present in hospitals Perfringens – Gas/wet gangrene o Anaerobic digestion of glucose leads to ethanol + CO2 (Fluid plus gas), thus wet or gas gangrene

Answer 35

The ecology of the normal gut flora is easily disrupted, leading to gastrointestinal disturbances such as diarrhoea, as often happens after treatment with antibiotics. Patients may also be infected with a variety of pathogens (some above). Noro-virus Every year there are epidemics of viral infections, often noro-viruses that produce a short period of vomiting and diarrhoea. Gastroenteritis (Food Poisoning) Gastroenteritis may follow consumption of food or drink contaminated with organisms or toxins, often of bacterial origin but already present in food. In both cases there is vomiting and diarrhoea. Onset is very rapid if toxins are ingested, within a very small number of hours, but may take up to 48 hours if caused by organisms. The most common organisms are strains of Salmonella, Campylobacter and Listeria. Toxins may come from Staphylococcus and Clostridium. Cholera Cholera is a severe acute infection, which is endemic in many parts of the world and periodically occurs in epidemics that are a real risk after natural disasters. The organism responsible, Vibrio Cholerae survives in water supplies and has a very specific effect on the ileum, leading to massive movement of water and salt into the lumen by active secretion. This leads to very serious diarrhoea, which after initial evacuation has a characteristic ‘rice-water’ appearance made up of intestinal secretions plus mucus. Rapid, severe dehydration follows, which is severely life threatening. Management must replace lost water and electrolytes with appropriate replacement fluids. Intestinal Parasites Intestinal parasites are common around the world and can cause a variety of effects. Some protozoans such as Giardia and Cryptosporidium cause Gastroenteritis. Other Helminth infestations may lead to Malabsorption amongst other effects. Bacteraemia vs. Septicaemia In Bacteraemia, the bacteria are rapidly cleared from the bloodstream (by liver/spleen macrophages). No symptoms are produced. In Septicaemia, bacteria are not cleared and multiply in the blood stream. Sepsis symptoms develop.

Answer 36

Enterotoxinogenic E. Coli (ETEC) is a major cause of Travellers’ diarrhoea in developing countries, caused by heat stable or labile toxins produced from this serotype, which results in severe, cholera-like watery diarrhoea. There is no inflammation and the condition is usually self-limiting.

Answer 37

``` Inflammatory Bowel Disease o Ulcerative Colitis o Crohn’s Disease o Diversion Colitis o Diverticular colitis o Radiation, Drug, Infectious, Ischaemic Colitis ``` Infection Infection with pathogen or toxin (Normal gut flora disturbed, immunosuppressed etc)

Answer 38

Small Intestines Chyme The stomach empties chyme into the duodenum, where it is conditioned: 1. Acidic 1. Corrected by HCO3- secreted from the pancreas, liver and Duodenal mucosa 2. HCO3- produced during the production of Gastric Acid 2. Hypertonic 1. Corrected by the osmotic movement of water into the duodenum across its wall 3. Partly digested 1. Digestion completed by enzymes from the pancreas and Duodenal mucosa, with bile acids from the liver. Absorption Absorption requires a large surface area, to which the luminal contents of the small intestine need to be exposed to through gentle agitation for hours. The small intestine is very long and the surface area for absorption is increased by millions of villi projecting into the lumen. Epithelial cells (enterocytes) arise by rapid division in the crypts between the villi, and migrate towards the tips, from which they are shed. They mature as they migrate and their luminal surface is covered with millions of micro villi, further increasing the surface area and forming the brush border. The brush border forms an ‘unstirred layer’ where nutrients meet and react with enzymes secreted by the enterocytes, completing digestion prior to absorption. Large Intestines The large intestines absorb water from the indigestible residues of chyme, converting it into semi-solid stool or faeces that is stored temporarily and allowed to accumulate until defecation occurs. The large intestines have teniae coli (thickened bands of smooth muscle, representing most of the longitudinal coat). They run the length of the large intestine, and because their tonic contraction shortens the part of the wall with which they are associated, the colon becomes sacculated or ‘baggy’ between the teniae, forming Haustra.

Answer 39

``` Small Intestine All sections: 4. Secrete protease / carbohydrase enzymes to complete digestion 5. Secrete Hormones 1. Secretin 2. Gastrin 3. Cholecystokinin ``` Duodenum 6. Bile and Pancreatic Secretions added 1. Ampulla of Vater 7. Secretes HCO3- to neutralise Chyme 8. Osmotic movement of water into the Duodenum, making Chyme more hypotonic 9. Absorption 1. Iron Jejunum 1. Absorption 1. Carbohydrates 2. Amino Acids 3. Small enough to soak through the villi 4. Fatty acids 5. Vitamins 6. Minerals 7. Electrolytes 8. Water Ileum 1. Absorption 1. Vitamin B12 2. Bile 3. Anything not absorbed by the jejunum ``` Large Intestine Takes about 16 hours to finish the digestion of food. 1. Absorption 1. Water 1. Any remaining absorbable nutrients 2. Vitamins created by colonic bacteria 1. Vitamin K, B12, Thiamine, riboflavin 2. Sends indigestible matter to the rectum ``` Rectum 3. Faeces 1. Stores and compacts faecal matter

Answer 40

Sugars Carbohydrates are ingested in the form of amyloses, amylopectins or disaccharides such as sucrose. 1. Amylose – Straight chain -1,4 bonds 2. Amylopectin – Branched with -1,6 bonds at branches -Amylases act on -1,4 bonds, and are secreted in saliva and by the pancreas. They yield glucose and maltose from amyloses, and -limit dextrins from amylopectins. Brush Border Enzymes (see above) complete breakdown to glucose. 1. Isomaltase 1. Breaks down branched molecules at -1,6 bonds 2. Maltase 1. Maltose  Glucose 3. Sucrase 1. Sucrose  Glucose/Fructose diamer 4. Lactase 1. Lactose  Glucose/Galactose diamer Glucose is absorbed actively using the energy from a Na+ gradient set up by Na/K/ATPase in the basolateral membrane. Glucose enters the epithelial cell across its apical membrane via a Na+/Glucose Symporter, SGLT1. This transporter also transports Galactose. Glucose then leaves the epithelia cell into the bloodstream across its basolateral membrane via facilitated diffusion through the GLUT2 transporter. Fructose enters the cell from the lumen via facilitated diffusion Amino Acids Proteins are digested to short peptides, 10-20 AA’s long (oligopeptides) in the stomach by Pepsin secreted from chief cells. In the Duodenum, Peptidases are secreted from the pancreas. Different enzymes ‘prefer’ breaking different bonds: 1. Pepsin 1. Bonds near aromatic AA side chains 2. Trypsin 1. Bonds near basic AA side chains 3. Chymotrypsin 1. Bonds near aromatic AA side chains 4. Carboxypeptidase 1. C-terminal AA’s with basic side chains Both amino acids and small peptides (2/3 AA’s) are absorbed. Further to this, in neonates our guts are ‘open’, so they are able to pick up whole proteins. This allows breast milk to confer passive immunity on babies via IgA absorption. ``` Active Uptake of Amino Acids There are at least five Na+/Amino acid Co-transporters (below), which work in a similar way to the uptake of glucose by using the Na+ gradient set up by Na-K-ATPase. 1. Small, neutral AA’s 2. Neutral AA’s, Basic AA’s and Cystine 3. Acidic AA’s 4. Imuno-AA’s 5.  AA’s (Mainly Taurine) ``` Some AA uptake is by facilitated passive diffusion. Dipeptides and tripeptides are taken up by an active mechanisms associated with pumping H+ into the lumen, which then returns by co-transport with the peptide. Fats Fats are relatively insoluble in water, making them tend to aggregate into large globules, preventing the effective action of digestive enzymes. Acid in the stomach exacerbates this. In the duodenum, bile acids enable fats to be incorporated into small (4-6nm) micelles, with fats in the middle and the polar components of bile acids on the outside. These micelles generate a high surface area for the action of lipases, which cleave the fatty acids from glycerol. The micelles also carry these products into the ‘unstirred layer’ immediately next to the mucosa, where fatty acids can be released to slowly diffuse into the epithelial cells. Once inside the epithelial cells they are reconstituted into triacylglycerols and re-expelled as chylomicrons, structured small particles made up of lipids covered in phospholipids, which facilitate the transport of fat in the lymphatic system from the gut to systemic veins. Salts and Water Sodium is taken up via diffusion into the cell, and actively transported across the basolateral membrane by Na-K-ATPase. This provides the driving force for the majority of absorption (see above). Chloride follows the movement of Na+. The movement of the two ions, coupled with all of the absorption, gives an Osmotic Gradient leading to the uptake of water. Minerals Calcium 1. 700mg/day absorbed out of 6g consumed (Just > 10%) 2. Enters the cell by facilitated diffusion 1. Low Intracellular concentration 3. Pumped out of basolateral membrane by Ca2+-ATPase 4. Both processes require Vitamin D 5. Stimulated by Parathyroid Hormone (PTH) Iron 1. 20mg a day of Iron is consumed 1. Mostly haem 2. Iron can only be absorbed in it’s ferrous form (Fe2+) 1. Gastric acid solubises iron complexes (Makes it ferrous) 2. Stomach also secretes Gastroferrin (Binds iron and keeps it ferrous) Intestinal mucosal cells secrete transferrin, which finds to ferrous iron (Fe2+) in the lumen. The complex is taken into cells by endocytosis, split and the iron is exported to the blood, where it binds again to transferrin. Vitamins 1. Water-soluble vitamins are absorbed via passive diffusion 1. Vitamin C, B vitamins 2. Vitamin B12 is absorbed with a co-factor in the terminal ileum only 1. Intrinsic Factor – Binds to B12 in the stomach to keep it soluble 2. Secreted by the stomach mucosa Pernicious anaemia occurs with Vitamin B12 deficiency. It occurs when there is damage to the stomach, preventing it from secreting intrinsic factor, or the terminal ileum has been damaged (e.g. Crohn’s) or removed.

Answer 41

1. The uptake of Na+ generates an osmotic gradient, which water follows. 2. Glucose uptake stimulates Na+ uptake, plus generates its own osmotic gradient So a mixture of glucose and NaCl will stimulate maximum water uptake. This is known as Oral Rehydration Fluid.

Answer 42

Intestinal contents must move very slowly (transit time in hours), whilst being gently agitated for effective absorption. This is achieved by a pattern of motility called Segmenting, which is very different to peristalsis. The small intestine is divided into sections, each with a pacemaker. The frequency of the pacemaker gets less from the duodenum to the terminal ileum (12 times a minute  8), a phenomenon known as the intestinal gradient. Each pacemaker drives a small section of intestine, causing intermitted contraction of smooth muscle along its length. These contractions separate the intestine into segments where the muscle is not contracted, whose contents are effectively mixed by movement from the portions that do contract. After a few seconds he contractions relax, and at the next pacemaker firing different areas contract. Segmenting itself does not propel contents along the intestine, merely mixes the contents. The intestinal gradient however means that there is a net movement, albeit slow, in a caudal direction.

Answer 43

Haustral Shuffling The large intestine is divided naturally into segments known as Haustra, as the circular muscles are more complete than the longitudinal, which have been reduced to taenia coli (thick circular muscle, thin longitudinal – only 3 layers). Contraction of the smooth muscle in the walls of the Haustra shuffles the contents back and forth, as the slow absorption of remaining water and salts forms faeces. The contents slowly progresses towards the sigmoid colon, with control like segmenting. Mass Movement Infrequently (once or twice a day), there is a Peristaltic, propelling pattern from the transverse through to the descending colon. This forces faeces rapidly into the rectum, which is normally empty, inducing the urge to defecate. Mass movement is often triggered by eating, the Gastro-colic reflex. They often also happen at certain times of the day, as “people like to be regular”.

Answer 44

Once mass movement has filled the rectum, the urge to defecate arises due to pressure receptors. Waves of contraction in the rectal muscle then force faeces towards the anus. Anal Sphincters Internal 1. Smooth Muscle 2. Parasympathetic control 1. Relaxes External 1. Voluntary Striated Muscle 2. Voluntary (normally) control 1. Relaxes Once both sphincters are relaxes, intra-abdominal pressure is increased (forces expiration) and there is an expulsion of faeces. The voluntary control of the external sphincter is overridden if rectal pressure becomes too high.

Answer 45

Inflammatory Bowel Disease 1. Ulcerative Colitis 2. Crohn’s Disease 3. Diversion Colitis 4. Diverticular colitis 5. Radiation, Drug, Infectious, Ischaemic Colitis

Answer 46

Ulcerative Colitis Ulcerative Colitis (UC) is an inflammatory disorder that affects the rectum and extends proximally, IN CONTINUITY (no breaks in inflammation) to affect a variable extent of the colon. There is a high incidence in the US, UK and northern Europe and it presents in young adults, more commonly in females. The mucosa of UC patients is dominated by Th2 (T-helper) cells, which produce Transforming Growth Factor (TGF) and IL-5. Ulcerative colitis presents with Rectal Bleeding, Diarrhoea and Abdominal Pain Crohn’s Disease Crohn's Disease (CD) is a condition of chronic inflammation, potentially involving any location of the GI tract from mouth to anus. There are two peaks in the incidence of CD, 1st at 15-30 years and 2nd at 60 years. The mucosa of CD patients is dominated by Th1 (T-helper) cells, which produce Interferon Gamma (IFN-) and IL-2. The presentation of Crohn’s disease depends on the disease’s location 1. Upper GI involvement 1. Nausea and vomiting 2. Dyspepsia 3. Small bowel obstruction 4. Anorexia, weight loss 5. Loose stools 6. Colonic Disease 7. Diarrhoea 8. Passage of obvious blood If the terminal ilium is involved, there may be anaemia due to poor absorption of Vitamin B12 Patients may have a Genetic Predisposition, and Environmental Factors may also play a role in developing Inflammatory Bowel Disease. 1. Genetic Predisposition 1. IBD1 2. NOD2/CARD15 3. Having one copy of a risk allele confers 2-4 fold risk for Crohn’s 4. Two couples of risk allele confers 20-40 fold risk for Crohn’s 1. Environmental Factors 1. NSAIDs 1. Altered intestinal barrier (?) 2. Early Appendectomy 1. Increased UC incidence 3. Smoking 1. Protects against UC 2. Increases risk of CD Triggers of Inflammatory Bowel Disease include: 1. Antibiotics 1. Gets rid of normal flora 2. Diet 3. Acute infections 4. NSAIDs 5. Smoking 1. Increase’s risk of Crohn’s 6. Stress

Answer 47

atory bowel disease 1. Colonoscopy 1. Biopsies of involved mucosa 2. Ulceration 3. Stool analysis 1. Parasites 2. Clostridium difficile toxin 3. Culture 4. Barium radiographs 5. CT scan 6. Capsule endoscopy 7. Plain X-Ray if bowel obstruction or perforation suspected

Answer 48

Macroscopic Changes Crohn's The involved bowel is usually thickened and is often narrowed. Deep ulcers and fissures in the mucosa may produce a Cobblestone appearance. Fistulae and abscesses may be seen, which reflect penetrating disease. Ulcerative Colitis The mucosa looks reddened, inflamed and bleeds easily. In severe disease there is extensive ulceration with the adjacent mucosa appearing as inflammatory (pseudo) polyps. Microscopic Changes Crohn's 1. Inflammation through all layers of the bowel (Transmural) 2. Increase in chronic inflammatory cells 3. Lymphoid hyperplasia 4. Granulomas (TH1 Response) Ulcerative Colitis 1. Superficial inflammation 2. Chronic inflammatory cell infiltrate in the lamina propria 3. Crypt abscesses 4. Goblet cell depletion

Answer 49

The differentiation between these two diseases can usually be made not only on the basis of clinical and radiological data, but also on the histological differences seen in the rectal and colonic mucosa obtained by biopsy. It is occasionally not possible to distinguish between the two disorders, particularly if biopsies are obtained in the acute phase. Such patients are considered to have Colitis of Undetermined Type and aEtiology (CUTE). Serological testing for anti-neutrophil cytoplasmic antibodies (ANCA) in UC and anti-Saccharomyces cervisiae antibodies (ASCA) in CD may be of value in differentiating the two conditions. Sometimes, an exact diagnosis can only be made after examining a surgical colectomy specimen.

Answer 50

Crohn’s 1. Colonoscopy 1. Performed if colonic involvement is suspected 2. Mild, patchy surface ulceration  Cobblestoning 3. Upper GI Endoscopy 4. Required to exclude oesophageal and Gastroduodenal disease in patients with relevant symptoms 5. Small Bowel Imaging 6. Mandatory in patients with suspected Crohn’s 7. Barium follow through 8. CT scan with oral contrast 9. Small bowel ultrasound 10. MRI 11. Asymmetrical alteration in the mucosal pattern with deep ulceration, and areas of narrowing or structuring 12. String sign of Kantor 13. Perianal MRI or Endoanal Ultrasound 14. Used to evaluate perianal disease 15. Capsule Endoscopy 16. Used in Crohn's disease patients who have a normal radiological examination Ulcerative Colitis 1. Colonoscopy 1. Biopsy is the ‘gold standard’ investigation for the diagnosis of UC 2. Assess disease activity and extent 2. Imaging 1. Plain Abdominal X-Ray to exclude colonic dilation 2. Other imaging techniques rarely used as endoscopy is preferred 3. Collar Button Ulcers 1. Ulcer through the bowel mucosa to the muscle, then up and down in a ‘T’ shape

Answer 51

Crohn’s Disease Induction of Remission Oral or IV Glucocorticosteroid Enteral Nutrition Anti-TNF antibodies (Infliximab) Maintenance of Remission Methotrexate, Azathioprine Anti-TNF antibodies (Infliximab) Perianal Disease Ciprofloxacin and Metrronidazole Azathioprine Anti-TNF Antibodies (Infliximab), bind to membrane bound TNF-α and induce immune cell apoptosis. Surgical Management Failure of therapy with acute or chronic symptoms Complications, e.g. dilation, obstruction, perforation, abscesses Failure to grow in children despite treatment Colectomy and ileorectal anastomosis may be performed. Ulcerative Colitis Distal Disease (Proctitis) Topical or suppository corticosteroidLeft Sided Colitis Topical corticosteroid enema Extensive Colitis Oral corticosteroids Infliximab Surgical Management Patients with complications / Corticosteroids dependence In acute disease, subtotal colectomy with end ileostomy and preservation of the rectum is the operation of choice.

Answer 52

``` Types of Imaging used to investigate the GI tract All these investigations below are used to investigate the abdomen. o Plain X-rays  Abdominal x-ray (AXR)  Erect chest x-ray (CXR) o Contrast studies  Barium swallow  Barium enema  Barium meal/follow through  Water soluble contrast studies o Ultrasound o Cross-sectional imaging  Computed Tomography (CT)  Magnetic Resonance Imaging (MRI) o Angiography ``` ``` The dose of radiation that these modalities give the patient, vary considerably. Ultrasound and MRI don’t use radiation while a CT scan can deliver a high dose of radiation (up to 15x the dose of an abdominal X-ray) Risks of radiation include; o Carcinogenesis o Genetic o Developmental risk to foetus ``` ``` Contrast Studies Contrast is used to define hollow viscera. Examples of contrast that is used include Barium and water soluble contrast (typically using iodine). Common GI contrast studies o Swallow o Meal o Follow through o Enema ``` A Barium Enema is a Barium study where the contrast medium is inserted rectally. This study enables the colon to be visualized. ``` Ultrasound o Use of sound waves to generate image  Frequency above audible range of human hearing (20 KHz)  Usually 2-18 MHz o Cheap compared to CT and MRI o Portable o Highly user dependent ``` Can be used to determine if a patient has Gallstones, or to see if the common bile duct is dilated (an indicator that there is an impacted gallstone in the duct). Abdominal ultrasound scan can also view the Liver and portal vein, even the Appendix. These scans are often difficult to interpret and the usefulness of a scan is often down to who is doing and interpreting the scan. GI angiography For both bleeding and ischaemia, being able to visualise the Blood supply to the GI tract is very useful. This is done by injecting a radio-opaque contrast agent intravenously and then using various modalities to capture the images. Here you can see the Aorta with the Coeliac trunk and the Superior Mesenteric arteries (and branches) very obviously shown. The Inferior Mesenteric artery and it’s branches are harder to see.

Answer 53

Abdominal X-ray Some structures that are potentially visible are shown to the right ``` Features of an AXR o Stomach o Small and Large Bowel o Soft Tissues o Liver, spleen, kidneys, psoas muscles, bladder, lung bases o Bones ``` Any part of a hollow tube is visible on an X-ray if it is filled with gas (Low density gas acts as a contrast). Fully fluid filled lumens are not visible. You can visualise the stomach (if gas filled) but more commonly we use this to visualise the small bowel.

Answer 54

``` Common Reasons for Requesting a Plain Abdominal X-ray o Acute abdominal pain o Small or large bowel obstruction o Acute exacerbation of IBD o Renal colic ```

Answer 55

The small bowel Usually occupies a central position on the Abdominal X-ray and can display its ‘circular folds’ or Valvulae conniventes, which appear as lines that appear to cross the whole of the bowel lumen Large bowel In contrast to the small bowel, this usually occupies a more peripheral position on the abdominal X-ray. It is often possible to see the Haustra on the X-ray, which appear as incomplete lines going across the lumen. Faeces can also appear on the X-ray and this can look like clouds in the lumen. Abnormal Gas Patterns on Abdominal X-ray Small and large bowel obstruction can be noted and follow the rule of 3/6/9. o The small bowel is said to be dilated when it is greater than 3cm diameter. o The large bowel when it is greater than 6cm o The Caecum (when the ileocaecal valve is working) is said to be dilated when it is greater than 9cm o This only applies when the X-ray shown is to scale. You can’t tell on these pictures! Small Bowel Obstruction This is small bowel. See its central position and lines going across the lumen (Valvulae conniventes) Small bowel usually presents with vomiting (early) and mild distension. Absolute constipation (not passing anything per rectum, even flatus) is a late feature. You vomit early simply because the obstruction is nearer the mouth than a large bowel obstruction. For the same reason constipation is a late feature in small bowel obstruction. There will be colicky pain that presents every 2-3 minutes. ``` Causes of small bowel obstruction o Adhesions o Hernias  Inguinal, Femoral, Incisional o Tumours o Inflammation ``` Large bowel obstruction The large bowel is seen more at the periphery of the X-ray and the lines going across the lumen are incomplete (Haustra). This presents with abdominal pain and distension with constipation as an early feature (nothing can pass into the rectum and out). The pain is also colicky but not as frequent as small bowel obstruction (every 10-15 minutes). Vomiting is a late feature of large bowel obstruction (it has further to travel to the mouth) and can be faeculant. ``` Causes of large bowel obstruction o Colorectal carcinoma o Diverticular stricture o Hernia o Volvulus o Pseudo-obstruction ``` Volvulus This is when a viscera twists around itself or more commonly when it twists around its mesentery. Most common is a Sigmoid volvulus or more rarely Caecal volvulus. When this twisting occurs the enclosed loop of bowel dilates and is at risk of perforating or cutting of its blood supply (which runs in the mesentery). ``` At this stage we would not expect you to be comfortable interpreting a volvulus on an abdominal X-ray. I would like you to be aware that it can happen though and what it means (basic clinical consequences). Other Abnormalities that can be visualized on an abdominal X-ray: o Pancreatitis (chronic) o Aneurysms with calcification o Nodes o Bones o Artifact o Foreign body o Kidney Stones ```

Answer 56

``` Perforation An Erect Chest X-ray can be useful in diagnosing perforated bowel. This can be caused by: o Peptic ulcer o Diverticular disease o Tumor o Obstruction o Trauma o Iatrogenic ``` The CXR needs to be erect because you are looking for the diaphragm to be elevated away from any other viscera (the Liver on the right) by the presence of air/gas in the peritoneal cavity. The air/gas will rise to the top of the cavity and so the patient needs to be sat up for 10 minutes prior to the X-ray to ensure this happens. The peritoneal cavity only normally contains a small amount of fluid, so the presence of air/gas is abnormal and could be the result of perforated bowel.

Answer 57

Abdominal CT o High dose radiation o Good spatial resolution (poor contrast resolution vs MRI) o Use of IV or oral/rectal contrast Can be done in a variety of anatomical planes ``` Magnetic resonance imaging (MRI) o Magnetic resonance imaging o First human MRI scan 1977 (in the US)  However developed by Sir Peter Mansfield (University of Nottingham) o No radiation o Good spatial and contrast resolution o Time consuming ``` Magnetic resonance cholangio-pancreatogram (MRCP) is an MRI scan that can visualize the Gallbladder and biliary tree.

Answer 58

Dyspepsia o Upper abdominal pain/Bloating o Chronic or recurrent pain or discomfort in the Upper abdomen Causes- There is some debate. o Chronic peptic ulcer disease o GORD o Malignancy o Functional/non ulcer  60% of dyspepsia.  No functional problem found to account for symptoms  Functional dyspepsia- 3 months of dyspepsia with no structural causes found What do you do? o Empirical acid suppression o Non invasive H-pylori testing/eradication o Early endoscopy Abdominal pain o Very common presentation (2% of all hospital admissions) o Multiple causes o Can be misleading- we need a sensible approach E.g Small bowel o Is it intra-peritoneal/extra-peritoneal?  Intra-Peritoneal o What embryological division does it belong to? o Intra-peritoneal structures refer pain to shared areas of the abdominal wall  Foregut – Up to 2nd part of Duodenum - Epigastric area  Midgut – Up until the distal third of the transverse colon - Peri-umbilical  Hindgut – Supra-pubic Foregut Pain Examples o Ulcers-epigastric pain  Commonly in the first part of the duodenum / lesser curve of the stomach o Pancreatits – Epigastric pain, back pain (retroperitoneal structure) o Gallstones – Epigastric pain, can also get Right Upper Quadrant (RUQ) pain. Often refered to as colicky pain (slight misnomer as the pain fairly constant). Midgut Pain Examples ‘Real’ colicky pain o Small bowel – Every 2-3 minutes o Large bowel – Every 10-15 mins ``` Small bowel obstruction o Vomiting (fairly early feature) o Abdominal distension o Xray may show  central abdominal distended loops  Circular folds (extending the full width of the bowel lumen) ``` Classic midgut scenario- Appendicitis! (Why epigastric  Localised pain) This should help you understand the difference between Visceral and Parietal pain Hindgut Pain Examples Sigmoid volvulus (Responsible for 8% of intestinal obstruction) o Twists on itself or its mesentery o Bowel obstruction- Absolute constipation o Blood supply interrupted- tissue death ``` Anorexia- Loss of appetite o Subjectively unpleasant food or surroundings o Anxiety o Anger/fear o Symptom of a physical disorder  Cancer (in particular GI tract)  Chemotherapy/certain Antibiotics  Pregnancy  Depression  Endocrine disorders o Symptom of a psychological disorder ``` Weight loss o Massive topic o Intentional/unintentional? o More than a 5% unintentional weight loss should be investigated Nausea o Subjective sensation of the need to vomit o Most people hate nausea more than vomiting! ``` Food Poisoning Common causes o Food poisoning (Staphlococcal, salmonella, E-coli) o Gastroenteritis (viral- Norwalk) o Cholecystitis o Appendicitis o Viral hepatitis o Pancreatitis o Intestinal blockage o Pain ``` ``` Constipation o Classified if less than 3 times a week (varies) o Change in bowel habit more important Causes o Diet o Medication (opiod analgesics, tricyclics) o Dehydration o Immobility o Disease-neurological (Stroke)  Diabetes  Colorectal Stricture o Functional  No reason for constipation  Possibly pain – Paediatrics ``` Diarrhoea o Different for individuals (good history necessary) o More stools or change in consistancy Categories o Secretory (Infection) o Osmotic (Lactose intolerance) o Abnormal Intestinal Motility (Thyrotoxicosis, IBS) o Exudative (Colitis, Cancer) o Malabsorption (Pancreatic enzyme/Bile Salt Deficiency) ``` Dysphagia o Difficulty swallowing (solids and liquids) o Differentiate from painful swallowing (Odynophagia) Broad categories o Difficulty initiating swallow  Neurological causes o Food sticking in oesophagus  Anatomical problems ``` ``` Bleeding From the top o Haematemesis o Acute/chronic peptic ulcer o Mallory-Weiss tear  Tear in oesophagus from repetitive retching o Oesophageal/Gastric Varices o Erosive Oesophagitis o Gastric/Oesophageal cancer ``` ``` From the bottom o Angiodysplasia  Vascular malformation of the gut blood vessels o Diverticular disease o Colonic carcinoma o Haemorrhoids/Anal fissure o Inflammatory Bowel Disease o Massive upper GI bleed  Malaena ``` ``` Abdominal distension o Fat o Fluid o Faeces o Flatus o Foetus Fluid-Ascites o Abnormal amounts of fluid collecting in the Peritoneal cavity  Liver failure  Portal hypertension  Cancer Flatus o Aerophagia- Air swallowing o Gas production in gut (especially if digestion has been incomplete) ``` ``` During practical o Hand signs o Jaundice o Spider naevi o Organomegaly ```

Answer 59

``` Mastication Saliva - Protects mouth Wets / Bacteriostatic / Alkaline / High Ca2+ Lubricates food for mastication and swallowing -Wet / Mucus Starts digestion -Sugars Swallowing Formation of bolus Rapid oesophageal transport ```

Answer 60

Storage Relaxes to accommodate food Initial disruption Contracts rhythmically to mix and disrupt Secretes acid and Proteolytic enzymes to break down tissues and disinfect Now known as Chyme Delivers Chyme slowly into the Duodenum

Answer 61

Dilution and neutralisation of Chyme Water drawn in from ECF. Stomach impermeable, Duodenum permeable. Alkali (bile) added from Liver and Pancreas Enzymes added from pancreas and intestine

Answer 62

Absorption of nutrients and electrolytes Fluid passes very slowly through the small intestine Large surface area Epithelial cells absorb molecules, some actively some passive -Often coupled to Na+ absorption Pass into hepatic portal circulation (First pass…) Absorbs the majority of water (1.5L vs. 0.15L large intestine)

Answer 63

Final absorption of water (0.15) Very slow transit Faeces form and accumulate in the descending and sigmoid colon

Answer 64

Faeces propelled periodically into rectum Urge to defecate Controlled relaxation of sphincters and expulsion of faeces

Answer 65

Difficultly swallowing. May be caused by problems with the oesophagus, e.g. musculature, obstruction by tumour or neurological, e.g. a stroke. Tumours of the oesophagus, high up are Squamous Cell Carcinoma, lower down are Adenocarcinomas.

Answer 66

Sphincter between the oesophagus and the stomach is weak, acid refluxes into the oesophagus and causes irritation and pain (heartburn).

Answer 67

Metaplasia of the lower oesophageal squamous epithelium to gastric columnar. This is to protect against acid reflux.

Answer 68

Portal venous system is overloaded due to cirrhosis, blood is diverted to the oesophagus through connecting vessels. This leads to the dilation of sub mucosal veins in the lower part of the oesophagus.

Answer 69

Area of damage to the inner mucosa of the stomach or duodenum, usually due to irritation from gastric acid.

Answer 70

Inflamed pancreas, causes considerable pain. Characterised by the release of amylases into the blood stream.

Answer 71

Liver cannot excrete bilirubin, which accumulates in the blood. If build up of bilirubin is due to excess haemoglobin breakdown it is Pre-hepatic Jaundice. If build up of bilirubin is due to bile duct obstruction and back up of bile causing liver damage it is Post-hepatic or Obstructive Jaundice

Answer 72

Precipitation of bile acids and cholesterol in the bladder forms gall stones. Often asymptomatic, but may move within the gall bladder causing painful Biliary Colic, or move to obstruct biliary outflow. Tumours of the pancreas may also obstruct outflow.

Answer 73

Inflammation of the appendix, presents as a sharp pain in the side at the same level as T10, which then localises to the right lower quadrant.

Answer 74

Inflammation of the peritoneum.

Answer 75

Present with Pain (in their back), vomiting and bloating.

Answer 76

Vascular structures in the anal canal that aid with stool control. When they become swollen and inflamed they are painful, itchy and blood may be present in stool.

Answer 77

Literally means ‘to fall out of place’. Prolapse is a condition where organs fall down or slip out of place. E.g. the rectum can prolapse.

Answer 78

Pressure is too high in the colon, producing an abnormal ‘outpouching’ to form a hollow. The sigmoid colon is the area most prone as the blood supply causes an area of weakness (?)

Answer 79

A pouch in the lower part of the small intestine, a vestigial remnant of the yolk sac. It can produce ectopic gastric mucosa that may then produce gastric acid, causing irritation.

Answer 80

The large intestine is a common site of malignancies, and colo-rectal cancer is a major cause of mortality.

Answer 81

``` Epidemiology Wide Geographical variation Incidence low in USA, and high around Caspian sea and parts of China 2% of malignancies in the UK Males > Females ``` Clinical Features Dysphagia Progressively worsening as tumour grows and occludes lumen Weight loss Investigation Endoscopy, Biopsy, Barium ``` Pathological Features Squamous cell carcinoma Commonest type May occur at any level Adenocarcinoma Uncommon Lower third Association with Barrett’s oesophagus ``` Prognosis Advances disease at presentation in most cases Direct spread through the oesophageal wall Only 40% resectable 5% five year survival

Answer 82

Gastric cancer is the second most common GI malignancy, with approximately 11,000 new cases in England and Wales each year. ``` Epidemiology Common 15% of Cancer deaths worldwide Men > Women Geographical variation Common in Japan, Columbia, Finland Associated with Gastritis Commoner in Blood Group A ``` Clinical Features Symptoms often vague Epigastric pain, vomiting, weight loss Investigations Endoscopy, Biopsy, Barium ``` Macroscopic Features Fungating Ulverating Infiltrative Linitis plastica ``` ``` Microscopic Features Intestinal Variable degree of gland formation Diffuse Single cells and small groups, signet ring cells ``` ``` Prognosis Early Gastric Cancer Confined to mucosa/sub-mucosa Good Prognosis Advanced Gastric Cancer Further spread Common in the UK ~10% 5 year survival Spread Direct Through gastric wall into duodenum, transverse colon, pancreas Lymph nodes Liver Trans-Coelomic Peritoneum Ovaries ``` H. Pylori and Gastric Cancer There is a general association of chronic inflammation with cancer. Gastric cancer is common in countries with high H. Pylori prevalence, e.g. Columbia. The association is supported by serological and epidemiological evidence. Gastric Lymphoma The commonest GI Lymphoma Starts as a low-grade lesion Strong association with H. Pylori Eradication of H. Pylori may lead to regression of tumour Prognosis much better than gastric cancer ``` Gastrointestinal Stromal Tumours Uncommon Derived from interstitial cells of Cajal The causative mutation, C-kit (CD117) makes it vulnerable to targeted treatment Unpredictable behaviour Pleomorphism Mitoses Necrosis ```

Answer 83

Adenomas Benign, neoplastic lesions in the large bowel (Dysplasia) Familial Adenomatous Polyposis (FAP) Gardner’s Syndrome Adenocarcinomas Polyps Anal Carcinoma ``` Large Intestinal Adenomas Benign, neoplastic lesions in the large bowel (Dysplasia) Macroscopic Sessile or pedunculated Microscopic Variable degree of dysplasia Malignant Potential Incidence increases with age in western population Genetic Syndromes ``` Familial Adenomatous Polyposis (FAP) FAP An autosomal dominant condition on Chromosome 5. By the time the patient is 20 there are thousands of adenomas in the large intestine, giving a high risk of cancer. Gardner’s Syndrome Gardner’s is similar to FAP, with bone and soft tissue tumours.

Answer 84

Colorectal cancer is the commonest GI malignancy, with ~25,000 new cases reported each year in England and Wales. ``` Macroscopic 60-70% rectosigmoid fungating/stenotic Microscopic Moderately different adenocarcinomas Mucinous Signet ring cell type ``` Spread Direct through bowel wall to adjacent organs (e.g. bladder) Via lymphatics to mesenteric lymph nodes Via portal venous system to liver ``` Staging Duke’s A – Confined to Bowel Wall B – Through wall, lymph nodes clear C – Lymph node involvement C1/C2 – Highest node clear/involved TMN Mutations FAP – Chromosome 5 Ras mutations p53 loss/inactivation ``` ``` Incidence Peak at 60-70 High in UK/USA, low in Japan Polyposis syndromes UC and Crohn’s ``` Aetiology Low residue diet, slow transit time, high fat intake, genetic predisposition. Outcome The survival time reduces with increasing Duke’s staging, and metastases to the liver are common in advanced disease. Other Large Intestine Tumours Carcinoid Tumour Rare and unpredictable neuro-endocrine tumour Lymphoma Rare, may be primary or spread from elsewhere Smooth muscle/stromal tumours Rare and unpredictable

Answer 85

Carcinoma of the Pancreas Morphology 2/3 in the head Firm pale mass with a necrotic centre May infiltrate adjacent structures, e.g. the spleen ``` Histology 80% are ductal adenocarcinomas Well formed glands Some acinar tumours contain zymogen granules All types have poor prognosis ```

Answer 86

Carcinoma of the Ampulla of Vater The bile duct is blocked with only a small tumour, leading to jaundice and early presentation when the tumour is still treatable. ``` Islet Cell Tumours Rare Insulinoma Hypoglycaemia Glycagonoma Characteristic skin rash Vasoactive Intestinal Peptideoma (VIPoma) Werner Morrison syndrome Gastrinoma Zollinger-Ellison syndrome ```

Answer 87

Tumours of the Liver Benign tumours are fairly rare Hepatic adenoma Bile duct adenoma/hamartoma Haemangioma ``` Malignant Hepatocellular carcinoma Cholangiocarcinoma Hepatoblastoma Common -> Rare (New cases per year in England and Wales) ``` Colorectal (25,000)  Stomach (11,000)  Pancreas (5,500)  Oesophagus

GastroIntestinal Flashcards

(111 cards)