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Stomach stretch makes what two things?
- 1. Ach - gastrin - makes acid.
- 2. Prostaglandins that make mucus
Both are protective for the stomach
Unique features about saliva.
- Stimulated by SNS and PNS (SNS makes thick secretions and PNS makes increased volume)
- Has a Cl-pump in the acinus
- Hypotonic so we can taste food
- Amylase but not essential like pancreatic lipase
- No protein digestion enzymes (therefore, tofu tastes like nothing)
Diphenoxylate for diarrhea?
Opiod agonist that binds to mu receptors in GI tract and slows motility. High doses combined with atropine to decrease physical dependance and euphoria
Secretory diarrhea treatment?
Bismuth sulfate and ocreotide
- Urea is converted to CO2 and NH3 and causes a pH increase - causing alkalinization of the urine.
- CO2 measured in a breath test.
Bilous vomiting in 24 hours due to intestinal obstruction after the duodenum. MoA?
Intestinal stenosis and atresia: absence of part of the bowel (e.g. formation of blind-ending proximal jejunem) and terminal ileum wraps around an ileocolic vessel.
Base excision repair (e.g. xeroderma pigmentosum) cytosine deamination creates unusal uracil binding. Steps to repair it?
- Glycosylase cleaves the misplaced uracil
- Endonuclease cleaves the 5' end and lyase cleaves the 3' end
- DNA polymerase and ligase fill in the single nt gaps
Colonic diverticula: MoA?
- Increased intraluminal pressure causes mucosa and submucosa to herniate through weak spots in the muscular layer.
- sigmoid colon
- Risk factor: chronic constipation
Pancreatitis due to alcohol or gallstones with pancreatic exocrine insufficiency lead to?
Malabsorption (fatty stools) due to failure to secrete adequate amylases, proteases, lipases.
Sx of gallstones obstructed in the cystic or common bile duct?
Biliary colic, jaaundice, cholangitis: fever, RUQ pain, + Murphy's sign.
Long history of gallstones and now shows air in the gallbladder and biliary tree. Where is the stone?
Gallstone ileus: Cholecystenteric fistula forms --> allows stone to go into the small bowel and dislodge in the ileum. Intestinal gas enters the gallbladder and biliary tree.
Vessels of the retroperitoneum?
Solid organs of the retroperitoneum?
Pancreas (except the tail), kidneys, adrenal glands
Hollow organs of the retroperitoneum?
2nd and 3rd part of the duodenum, ascending and descending colon, rectum, ureters, bladder
Lactase administration to lactose intolerant patients. Lab values?
- Increased osmotic stool gap (osmolarity increases due to decreased absorption of substances)
- Increased breath H+ content (osmotic diarrhea)
- Decreased stool pH
Prevalence of a disease directly and indirectly depends on what factors?
- NPV (inverse relationship with prevalence)
- Abnormal development of anorectal structures (small dimpling instead of an anus opening)
- Inability to pass meconium
- Meconium can exit from urethra if fistula present = GU problems
- Associations: VACTERL (less common than GU sx)
- vertebral defects
- anal atresia
- cardiac problems
- TE fistula
- esophageal atresia
- renal problems
- limb defects
Systemic sclerosis pathogenesis?
CD4 accumulation, increased tissue fibrosis due to collagen deposition
What does Campylobacter show on a stool test?
- Absence of ova and parasites
- Inflammatory: watery and then bloody
Toxins of C.difficile.
- Toxin A (enterotoxin): mucosal inflammation, loss of water with diarrhea, mucosal death
- Toxin B (cytotoxin): actin depolymerization, loss of cytoskeleton integrity, mucosal necrosis
Which drugs cause mitochondrial toxicity?
Crohn's dz and gallstones relationship?
- Normal: bile acids are produced in liver, excreted with bile and reach terminal ileum become micelles with fat and reabsorbed in the liver again.
- Crohn's: damaged terminal ileum - no bile acid reabsorption = gallstones
Arsenic poisoning (garlic odor on breath) treatment?
Which antibody level will differ 1 month after giving a live and a killed vaccine?
Mucosal IgA (immune protection)
Adverse effects of protease inhibitors
- Cushing's (lipodystrophy = redistribution of fat)
- P450 inhibition
Which Hep viruses are mostly anicteric?
Hep A and E (fecal-oral)
How does Giardia cause injury?
Injury to the duodenal and jejunal mucosa by adhering to the intestinal brush border, severe IgA deficiency predisposes (no adaptive immunity)
Penetrating injuries to the abdomen cause abscesses of what bacteria?
Mixed aerobic and anaerobic bacteria
Histo of acute viral hepatitis?
- Ballooning degeneration (hepatocyte swelling)
- Councilman bodies (eosinophilic apoptotic hepatocytes)
- Hep A and E
Histo of chronic viral hepatitis?
- Nodular regeneration
- Hep B and C
Mechanism of esophageal varices?
Increased venous pressure associated with cirrhosis
Mechanism of Mallory-Weiss syndrome?
- Increased intraluminal/abdominal pressure caused by vomiting, retching.
- Hiatal hernias also a cause
Mechanism of cirrhosis-related hepatic encephalopathy
- Increases NH3 deposition due to waste products (GI bleeding, hypovolemia, hypokalemia, metabolic alkalosis, infection, hypoglycemia)
Mechanism of Zenker's diverticulum?
- Cricopharyngeal muscle dysfunction (decreased relaxation of pharyngeal muscles during swallowing).
- Increased intraluminal pressure causes mucosa to herniate through
Southwestern blot: substance and probe?
- DNA binding proteins (c-jun and c-fos)
- dsDNA probe
- Proto-oncogene: codes for a membrane-G protein which activates MAP kinase pathway and activates transcription.
- Doesnt directly bind to DNA
Processes that occur in the mitochondria
- 1. Glycolysis/Gluconeogenesis
- 2. B-oxidation
- 3. TCA
- 4. Urea cycle (OTC)
Which cells cannot use ketone bodies?
- 1. RBCs have no mitochondria
- 2. Hepatocytes have mitochondria, but lack succinyl-coA enzyme
Inactivating Hep A virus mechanisms
- 1. irradiation
- 2. water chlorination
- 3. boiling for 1 min
- 4. bleach
- 5. autoclaving (120C) for 20 mins
Bioavailability of drug by IV route
Bioavailability of drug by oral, IM or other route besides IV
- Area under oral curve x IV dose/Area under IV curve x oral dose
Gallbladder stones during pregnancy or use of OCP
- 1. Estrogen upregulates HMG-CoA reductase increasing cholestrol synthesis
- 2. Progesterone-induced gallbladder hypomotility and decreases bile secretion
Gallbladder hypomotility causes what stones?
Biliary stones (decrease in bile reabsorption)
- Cholinergic and vagal stimulation
- Presence of thought, sight, smell, food
Gastrin stimulation and stomach distention increases acid release
- Inhibits gastrin release
- Ileum and colon release peptide YY, which binds to ECLs
Adenamotous polyp formation association with what factor
Recurrence prevention of ulcers
- Chr 6.
- HFE gene encodes a HLA-class I transporter that affects Fe absorption in the duodenum
Crohn's disease affected with what transcription factor?
NF-kB causes cytokine production
Hox genes encode what factors?
Transcription regulators encoding morphogenesis.
Abnormal midgut rotation around SMA?
- 1. Intestinal obstruction
- 2. Midgut volvulus (intestinal ischemia
- 1. Duodenal atresia (ischemia)
- 2. Intestinal obstruction distal to duodenum (ampulla of Vater)
Function of MMC (migratory motor complexes)
- Peristalsis waves from the stomach to the small intestine when food is not present.
- Sweeps undigested food and maintains low bacterial counts in the SI.
Absence of MMC
- Increased intestinal bacteria
- Decreased gastric emptying
- Slows duodenal motility
Identifies C.diptheria from other oropharynx flora
CAMP factor produced by S.agalactaie - used to distinguish between Group A and B strep
Fats, proteins, and carbs together release what hormone
Treatment of nausea with anti-neoplastic agents?
- 1. 5HT3 antagonists (Ondasteron)
- 2. Cental dopamine antagonists (Metachlopromide)
Acute hemorrhagic pancreatitis
Necrosis and hemorrhage --> Septic shock
- NK-1 antagonist and block susbtance P
- (NK receptors present in the brainstem and control the emetic reflex)
- Treats nausea and vomiting with moderate anti-neoplastic agents
- Accumulation of acylcarinitines in the urine
- B-oxidation impairment - low ATP levels
- Low ATP = deficiency of urea cycle
- Urea cycle def = hyperammonia
- Fasting hypoglycemia (low glucagon)
- No ketone bodies
- Inhibits gastric acid secretion via somatostain
- Inhibits gastric emptying
- Contraction of gallbladder and relaxation of sphincter of Oddi
- Digestion in the duodenum
- Increases production of hepatic bile
n.b. CCK antagonist can also increase CCK levels
Reyes syndrome pathophysiology
- Encephalopathy and hepatic failure
- Mitochondrial dysfunction: impairs B-oxidation and oxidative phosphorylation (glycolysis)
Causes of jejunal and ileal obstruction
- Ascaris infection
- Tumors - intessuception
- Midgut volvulus
What strengthens gastric mucosal barrier?
- Mucus (impedes H+ ion flow)
- Gastrin (mucosal growth)
Acini in sublingual glands
Acini in the parotid gland
Acini in the submucosal glands
Serous + Mucus
What stimulates gastric acid secretion
- 1. Gastrin
- 2. Ach (vagal stimulation)
- 3. Histamine
What inhibits gastric acid secretion and stimulates pancreas to release HCO3?
Enzymes in hepatic injury caused by acetaminophen
- Increased AST and ALT
- Normal amylase (no pancreatitis)
- Normal ALP (no injury to the bile ducts or biliary tree)
Pressure on splenic a. affects what artery
- Short gastric
- (left gastroepiploic anastomoses with right gastroepiploic)
How is NH3 excreted?
- Mainly by conversion from NH3 to urea by the urea cycle in the liver
- (Liver disease inhibits this causing encephalopathy)
- Excreted as free acid (NH4+) by the kidney (minimally)
H. pylori damaging gastric mucosa
- Urease causes breakdown of urea into NH4+ increasing acidity, and feedback inhibition onto gastrin.
- Bacteria can survive acid environment of stomach
- Damage to mucosa causes ulcer formation
Sclerodactaly and esophageal dysmotility
Increased fibrosis causes thickening of skin in esophagus, making it difficult to swallow, causes heartburn, absence of persistalsis and LES
Obstructive jaundice due to gallstones
- Increased conjugative bilirubin
- Increased urine bilirubin (colour of urine darkens)
- Decreased urobilinogen (therefore, clay coloured stools)
Pigmented gallstones causes
- Hemolytic anemias
- Clonorchis sinesis (liver fluke)
Multiple nests of benign, disorganized hepatic parenchyma containing biliary components
- Focal nodular hyperplasia
- (variant of HCC)
GE junction seen above the esophageal hiatus of the diaphragm
Sliding hiatal hernia
Paraesophageal hiatal hernia
- Part of gastric cardia slides up into the thorax, alongside the esophagus.
- GE junction is at the esophageal hiatus (not displaced)
Treatment of traveller's diarrhea
Fluoroquinolones (mostly for gram negatives)
- Failure of recanalization of the embryonic duct = intestinal obstruction
- Bilous vomiting after feeding
- Two air-filled structures in the stomach
- No distal air bowel gas
- Occurs when oral foods are introduced in preemies mostly
- Ischemic injury of the gut leading to septic shock
- Affected mostly with giving formula rather than breastmilk - lack of maternal antibodies.
- Do pass meconium on 1st day
Diarrhea that is treated with nutrient supplementation
- Osmotic diarrhea
- (unabsorbed solutes draw water in)
Treat of acute choecystitis with a codeine drug
- Meperidine: M3 antagonist so it causes relaxation of the spincter
- (Morphine causes contraction of the sphincter, even though a good pain reliever)
Cystic-fibrosis induced pancreatitis
Reduced secretions causes thickened mucus plugs = accumulation of pancreatic enzymes
Can occur in the SI and produce enough acid to cause peptic ulcers and then bleeding
Hepatic fibrosis without fat accumulation, and accumulation of small-chain dextrin like material in the hepatocytes.
Cori's disease: debranching enzyme defect = incomplete glycogen degradation (a,1,6 glucosidic bonds cannot be broken)
Why does RNA polymerase make many errors during replication?
Doesn't have 3'-5' exonuclease activity
Ulcerative colitis leads to colorectal cancer long-term. Features?
- Arises from dysplastic flat lesions (no polyps)
- Early p53 mutations and late APC gene mutations
- Multifocal in nature
- Histo: mucinous and/or signet ring morphology
Interupting migration of neural crest cells damages what part of the GI tract first
- Hirschrpung's dz: Rectum
- Vagal stimulated: NC cells give rise to Meissner's (submucosal) and Auberbach plexi (myenteric)
- NC cell migration moves caudally
- Complication of pancreatitis
- Fluid-filled with enzymes and inflammatory debris
- Walls have granulation tissue and fibrosis, no epithelium
Causes of esophagitis and findings
- Herpes simplex - small vesicles with punched out lesions, eosinophilic intranuclear inclusions
- CMV - linear ulceration, intranuclear and intracytoplasmic inclusion bodies
Ulcerative colitis patient develops bloody diarrhea and abdominal distention. Dx?
- Toxic megacolon - supportive treatment
- (barium enema and colonscopy can cause perforation)
Mast cell proliferation in multiple organs. Massive release of histamine - acts on parietal cells to stimulate gastric acid - inactivates pancreatic and intestinal enzymes - diarrhea, etc.
- Toxin mediated watery diarrhea (increased cAMP)
- Not invasive
- No blood or pus (leukocytes) on stool microscopy
Lactase deficiency (biochemical process)?
- Enzyme: B-galactosidase
- Galactosyl-B-1,4glucose --> Galactose
Opiod adverse effects in GI
Contraction of smooth muscle cells of the sphicter of Oddi, increasing pressure in bile duct and gallbladder (biliary colic)
- Located on posterior midline distal to the dentate line
- Severe tearing pain when needed to pass stool
- Due to low fibre diets and constipation
Polyps progression to cancer process:
- 1. APC gene mutation causes adenomatous polyps to form from normal colonic mucosa
- 2. K-ras mutation = cell proliferation (size increase in polyps)
- 3. p53 mutation - last step from adenoma to carcinoma
Where are fats and fat-soluble vitamins digested and absorbed?
Duodenum and jejunem
- Type III H.S.
- 5-10 days after drug given
- Sx: arthralgias, utricaria, proteinuria, lymphadenopathy
Crohn's disease molecular factors
Increased TH1 helper cells = increases IFN-gamma, IL-2, and TNF causing intestinal injury.
Elevated serum transaminases, neurological sx, no viral serologies, no use of alcohol or drugs.
Location of promoter regions?
25-70 bp upstream from its associated gene
Location of enhancers/repressors?
Variable: upstream, downstream, or within the transcribed gene
- Mucosal invasion by entering M cells via Peyer's patches
- Escapes phagosome and enters epithelial cells to release shiga toxin
Use of primaquine with chloroquine
- Chloroquine has no effect against latent hepatic infections (P.vivax and P.ovale)
- Primaquine used to treat these and prevent relapse
- Cause: E.granulosus (tapeworm)
- Aspiration of cyst leads to anaphylactic shock
- Gene mutation in p53
- Prone to HCC
- Mucoid, secretory diarrhea
- Mass found in sigmoid colon (obstruction)
- Lower intestinal bleeding
- Progresses to adenocarcinoma
H.pylori and duodenal ulcers
- Antral gastritis: decreased # of somatostatin-antral producing cells
- High gastrin causes high acidity
H.pylori and gastric ulcers
- Dont need an increase level of acid
- Normal acid levels are sufficient as in the stomach
- Destruction of mucosal barrier due to bacteria
Secretion of gastrin
Secretion of HCl and IF
- G cells of the gastric antrum
What happens with vagotomy?
- Receptive relaxation is inhibited (cannot relax when food enters the stomach from the esophagus)
- Peristalsis can still occur
Cholera toxin mechanism
Activates AC increasing cAMP in the intestinal crypt cells activating Cl- secretory channels
Micelles solubilize what?
Fat soluble vitamins
- n.b. Bile acids have a co-dependent Na+ transport in ileum
- Glycerol is a water soluble molecule of lipid digestion and doesnt need micelles
Secretion from exocrine pancreas (enzymes)
- Major anion is HCO3 in pancreatic secretions (higher than plasma)
- Cl- is lower than plasma
- Stimulated by presence of fatty acids in the duodenum
- Secretin stimulates pancreatic HCO3 secretions
- CCK stimulates pancreatic enzyme secretions
Oral glucose better than IV glucose
Releases GIP which causes release of insulin from endocrine pancreas
Features of saliva
- High HCO3- relative to plasma
- Presence of a-amylase and lingual lipase
- No proteases
Contamination from poultry foods causing watery diarrhea
- Campylobacter (take couple of days to develop)
- Salmonella non-typhi
- S.aureus (immediate, within hours)
Where are Kaposi's sarcoma nodules found?
All over the body, including skin and GI tract mucosa
Spontaneous bacterial peritonitis
- Seen in 10% of patients who have cirrhosis with ascites
- Ascites: culture medium for bacteria that invade the bowel wall or spread to serosa
Entire eroded gastric mucosa with erythematous, cobble-stone appearance. Stomach is small and shrunken.
Signet cell adenocarcinoma
11-month old with no stool on diaper and distended abdomen
At birth, no stool on diaper and distended abdomen
Gastric defenses against peptic ulcer disease
- HCO3 secretion into the mucus
- Rapid gastric epithelial regeneration
- Epithelial cell mucus secretion
- Increased mucosal blood flow
n.b delayed gastric emptying promotes ulcers by keeping acid in there
Which bug causes diarrhea in young children that can be replaced with adequate fluids?
Complications of diverticulosis
Diverticulitis producing an abscess, peritonitis or both.
Cancers of the GI tract associated with AIDS and non-AIDS.
- B cell neoplasms:
- a) Kaposi's sarcoma
- b) non-Hodgkin's lymphoma
- c) anorectal SCC
Non-AIDS: MALT lymphomas with sprue, H.pylori infection
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