GIT Pathology 1 to 10
What is the aetiology of acute pancreatitis?
- Metabolic – Alcohol 5% (UK), 65% (US), M:F = 6:1, drugs eg. azothioprine, hyperlipoproteinemia, hypercalcaemia,
- Genetic – trypsinogen and trypsin genes
- Mechanical – Gallstones 35-60%, M:F = 1:3, trauma, iatrogenic/intraoperative/ERCP
- Vascular – shock, atherosclerosis, vasculitis
- Infectious – mumps
What is the suggested pathogenesis of acute pancreatitis?
- Autodigestion of pancreatic substance by inappropriately activated pancreatic enzymes
- 3 mechanisms
- Pancreatic duct obstruction eg. by impacted gallstone => accumulation of lipase in interstitium => local fat necrosis => release of proinflammatory cytokines => leaky vessels + oedema => vascular insufficiency and ischaemic damage to acinar cells
- Primary acinar cell injury eg. alcohol, mumps, trauma, drugs, organ insufficiency aftershock/ischaemia
- Defective intracellular transport of proenzymes within acinar cells – digestive enzymes and lysosomal hydrolases intermingled causing release of activated enzymes. Human mechanism not clear
- Bold to pass
What are the laboratory findings of acute pancreatitis?
- Marked elevation of serum amylase in first 24 hours
- Rising serum lipase within 72-96 hours
- Glycosuria – 10% cases
- Hypocalcaemia – poor prognostic sign if persistent
- Acute renal failure
- Bold PLUS 2 others
What are the pathological features of Ulcerative Colitis?
- One of two disorders that compromise inflammatory bowel disease (IBD)
- Severe ulcerating inflammatory disease
- Limited to colon and rectum.
- Continuous distribution (Starts in colon and extends continuously – No skip lesions)
- Extends only into mucosa and submucosa (ie not trans mural)
- Pancolitis if entire colon affected, limited distal disease eg ulcerative proctitis
- Superficial broad based ulcers
- Malignant potential
- Toxic megacolon
- Bold PLUS 2 others
What extra-intestinal manifestations occur in ulcerative colitis?
- Extra-intestinal Manifestations
- Polyarthritis, sacroiliitis, ankylosing spondylitis
- Skin lesions
- Primary sclerosing cholangitis
- 4 for a pass
Describe the pathogenesis of pseudomembranous colitis.
- Disruption of normal bowel flora (ab’s – esp. 3rd gen ceph) allowing overgrowth of C. difficile
- C. difficile elaborates toxins that cause:
- Ribosylation of small GTPases
- Disruption of epithelial cytoskeleton
- Tight junction barrier loss
- Cytokine release
- Denuded surface epithelium
- Superficial lamina propria contains dense infiltrate of neutrophils & occasional fibrin thrombi in capillaries
- Damaged crypts are distended by mucopurulent exudates that erupt “volcanically”
- Coalesce to form the pseudomembrane
- Toxin PLUS one other bold
What are the clinical features of pseudomembranous colitis?
- Causes fever, (leukocytosis), profuse watery diarrhoea, abdo pain
What is the pseudomembrane?
- Pseudomembrane is an adherent layer of inflammatory cells and debris at sites of colonic mucosal injury
- Bold points
What are the aetiological factors in acute pancreatitis?
- Metabolic: alcoholism, hyperlipoproteinemia, hypercalcaemia, drugs, genetic
- Mechanical: trauma, gallstones, iatrogenic injury
- Vascular: shock, atheroembolism, polyarteritis nodosa.
- Infectious: mumps, coxsackie, mycoplasma
- Require Alcohol, gallstones and 2 others
Describe the cellular morphology of acute pancreatitis.
- Range from trivial inflammation and oedema to extensive necrosis and haemorrhage.
- Microvascular leakage with oedema, lipolysis by enzymes, acute inflammatory reaction, proteolysis of parenchyma, destruction of blood vessels.
- Fatty acids released combine with calcium to precipitate as salts, acini, ducts and islets can all be involved.
- Red black haemorrhage mixed with yellow white fat necrosis.
- Extra pancreatic fat necrosis eg in omentum
- Peritoneal fluid with fat globules
- Require Inflammatory changes and lipolysis
Describe the pathogenesis of acute calculous cholecystitis.
- Acute Calculous (90% of all)
- Obstruction by stones, stasis- activates hydrolases
- Lecithins -> (mucosal Phospholipases) -> lysolecithins
- Disrupts glycoprotein mucous -> epithelium exposed to bile salts
- Prostaglandin release -> inflammation, mucosal and mural
- Dysmotility & raised intraluminal pressure
- Bacterial infection secondary to stasis
- 3 out of 6
How does acalculous cholecystitis differ from this?
- Acalculous (10%) – rarer, in predisposed individuals, slower often masked
- Ischaemia, end arteries (cystic)
- Other promoting features – sludging micro-crystals, stasis, local inflammation, distension
- Sepsis with hypotension, immunosuppression, major trauma and burns, diabetes, infection, severe atherosclerosis (drugs/ABs- vasculitic)
Describe the clinical features of acute cholecystitis.
- Right upper quadrant or epigastric pain,
- Mild fever, anorexia, tachycardia, sweating, nausea, and vomiting, tender RUQ (Murphy’s)
- 4 out of 7
What are the predisposing conditions for the development of ischemic bowel?
- aortic dissection
- iatrogenic – angiography or aortic reconstruction
- Hypercoagulable state.
- Oral Contraceptive Pill
- Aortic atheroembolism
- AT III deficiency.
- Intraperitoneal sepsis
- Invasive neoplasms
- abdominal trauma
- cardiac failure
- vaso constrictive drugs
- internal or external herniation
- Simple list of 6 or more must contain examples of each of first 3 categories = straight pass
- Headings + good examples of each = better pass
What are the clinical features of transmural infarction?
- Bloody diarrhoea, melanotic stool
- Vascular collapse
- Absent bowel sounds
- Abdominal rigidity
- Pain PLUS any other 3
What are the causes of acute pancreatitis?
- Includes alcohol
- Idiopathic (probably genetic basis)
- Identify alcohol and gallstones PLUS two others to pass
Describe the pathogenesis of acute pancreatitis?
- Arises as a result of autodigestion by inappropriately activated pancreatic enzymes.
- Trypsinogen is activated to trypsin. This in turn activates prophospholipase and proelastase, prekallikrein thus activating kinin system, and Hageman factor thus activated clotting and complement systems
Three potential pathways for initiation of pancreatic pathways:
- pancreatic duct obstruction
- primary acinar cell injury
- defective intracellular transport of proenzymes within acinar cells
- Autodigestion and key role of activation of trypsinogen as triggering factor to pass
By what mechanisms may Helicobacter pylori cause peptic ulcers?
Prompt: What does H. pylori produce which can help cause ulceration?
- H. pylori secretes urease, which generates free ammonia; and a protease which breaks down glycoproteins in the gastric mucosa.
- H. pylori makes phospholipases -> damage surface epithelial cells glycoprotein complexes.
- H. pylori enhances gastric secretion and impairs duodenal bicarbonate secretion. This enhances metaplasia.
- Several H. pylori proteins are immunogenic -> evokes strong immune responsein the mucosa. Activated T and B cells are both seen in chronic gastritis caused by H. pylori.
- Thrombotic occlusion of surface capillaries is promoted by a bacterial platelet activating factor.
- Other antigens (including lipopolysaccharide) recruit inflammatory cells to the mucosa.
- Damage to the mucosa is thought to permit leakage of tissue nutrients into the surface microenvironment, thereby sustaining the bacillus
- Bold to pass
What complications may arise from peptic ulcer disease?
- Bleeding (15-20%of patients), -> 25% of ulcer deaths
- ~ 5% of patients
- -> 2/3 of ulcer deaths
- Obstruction from oedema and or scarring
- ~ 2% of patients
- Mostly due to pyloric channel ulcers
- Rarely causes complete obstruction with intractable vomiting & incapacitating, crampy abdominal pain
- 2 out of 3
What is the pathogenesis of pernicious anaemia?
- Immunologically mediated (possibly autoimmune) destruction of gastric mucosa > chronic atrophic gastritis.
- Likely an autoreactive T-cell response > gastric mucosal injury and production of autoantibodies which may exacerbate epitheleal injury
- Loss of parietal cells leads to reduced intrinsic factor production which in turn leads to reduced Vit B12 (cobalamin) absorption from the gut, resulting in macrocytic anaemia
- Also 3 types of antibodies present in many patients with P.A however their role in pathogenesis is unclear. Type 1 Ab blocks B12-IF binding. Type 2 blocks B12-IF complex binding to ileal receptors. Type 3 Ab recognises alpha and beta subunits of gastric proton pump. Type 3 most likely a response to gastric injury rather than causative
- Must state immunologically mediated to pass
What are the clinical manifestations of the disease?
- Insidious onset (due to large existing B12 stores) and progressive unless treated
- Moderate to severe megaloblastic anaemia. Weakness tiredness, pallor
- Leukopenia and thrombocytopenia
- Mild jaundice (ineffective erythropoiesis and enhanced peripheral haemolysis
- Atrophic glossitis (shiny glazed appearance)
- Neurologic manifestations may include spastic paraparesis, sensory ataxia and severe paraesthesias (more commonly in lower limbs
- Bold to pass
List the types of E. Coli enteritis and describe their features.
- Enterotoxic E coli (ETEC)
- Food and water, traveller’s
- LT heat labile toxin, adenyl cyclise -> increasing cAMP -> increasing Cl- secretion and decreasing absorption (cholera like)
- ST heat stable toxin, guanylate cyclase -> incr cGMP
- Enterohaemorrhagic E coli (EHEC)
- Beef esp. ground, milk vegetable
- O157:H7 and non O157:H7
- Shigella like toxin
- Large outbreaks, bloody diarrhoea, haemolytic uraemic syndrome
- Thrombotic Thrombocytopenic purpure (2%)
- Enteroinvasive E. Coli (EIEC)
- Food, water, person to person
- No toxins, invades mucosa, colitis
- Enteroaggregative E. coli (EAEC)
- Adheres via adherence fimbriae
- Dispersin (removes –ve charge/ protection)
- Shigella like toxin and ETEC ST toxin
- Non bloody diarrhoea, prolonged in AIDS
- 2 out of 4 groups to pass
- 1 feature of any 2