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GI Pathophysiology
Diverticular disease, cholelithiasis, pancreatic disease (exocrine)
126
Medical
Graduate
02/27/2010

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Cards

Term
80% of acute pancreatitis in Western countries is associated with what two underlying conditions?
Definition
Biliary tract disease and alcoholism
Term
In the absence of biliary tract disease or alcoholism, what are other potential causes of acute pancreatitis
Definition
Pancreatic carcinomas, Ascariasis or Clonorchis infection, congenital malformations of the pancreatic duct, drugs (thiazide diuretics, estrogens, lasix, others), mumps virus or coxsackivirus infection, ischemia, or trauma
Term
Regardless of different etiologies, what is the common precursor to acute pancreatitis?
Definition
Acinar cell injury, causing release of proenzymes and subsequent activation, especially proteases (trypsinogen->trypsin, other types)
Term
Trypsinogen is converted to trypsin by what enzyme, secreted by the duodenum?
Definition
Enteropeptidase, although trypsin has auto-catalytic properties as well, so once some trypsin is activated it can activate more trypsinogen
Term
In addition to auto-digestion, what other action of trypsin causes damage to pancreatic blood vessels and parenchymal tissue?
Definition
Conversion of prekallikrein to kallikrein and Hageman factor, both activating clotting and complement cascades that can lead to further inflammation and small vessel thromboses in the pancreas
Term
The pancreatic duct empties into the duodenum via this structure
Definition
Ampulla of Vater
Term
This type of necrosis seen in pancreatitis is a result of lipase activity, leading to deposition of fat in surrounding tissue
Definition
Fat necrosis
Term
True or false: IL1B, IL6, TNFa and substance P all play an important role in inflammation due to pancreatic duct obstruction
Definition
True, promotes edema formation from leaky microvasculature and ischemic injury to acinar cells
Term
This muscle controls the opening of the ampulla of vater
Definition
Sphincter of Oddi
Term
True or false: normally, pancreatic zymogens and lysosomal enzymes are transported together and activated prior to entry into the duodenum
Definition
False, they are typically transported through the duct and into the small bowel in separate vesicles, then interact, in aberrant processes they join before, activation occurs causing pancreatic damage
Term
What is the difference in prognosis of chronic vs. acute pancreatitis?
Definition
the parenchymal damage is permanent in chronic pancreatitis, reversible in acute pancreatitis
Term
True or false: the primary symptom of acute pancreatitis is abdominal pain
Definition
True, it is a medical emergency, also can present with DIC, leukocytosis, hemolysis, ARDS and diffuse fat necrosis in the peritoneum
Term
What lab values are helpful during the first 24 hours and 72-96 hours respectively?
Definition
Amylase, then lipase
Term
True or false: "rest" is the recommended tx for acute pancreatitis
Definition
True, food and fluid rstriction with supportive therapy allows the pancreas to recover, sequelae include pancreatic pseudocysts or pancreatic abscesses that can cause subsequent attacks
Term
The most common cause of chronic pancreatitis is:
Definition
EtOH abuse, there are some hereditary causes but these are rare, resulting from mutations in the PRSS1 or SPINK1 genes that facilitate trypsin inactivation via a receptor and inhibitor, respectively, these can also cause acute pancreatitis
Term
In contrast to the hemhorrage and fat necrosis seen in acute pancreatitis, the most common pathologic finding in chronic pancreatitis is:
Definition
Parenchymal fibrosis, though pancreatic islets are spared
Term
True or false: Congenital diverticula are uncommon pathologies in the general population
Definition
False, in the ascending colon diverticula are not uncommon, most diverticular disease occurs in the sigmoid colon (95%)
Term
Unless otherwise specified, colonic diverticula contain only these two layers of the intestinal wall
Definition
Mucosa and sub mucosa, some may have an attenuated muscularis propria but it is commonly missing
Term
What two factors are implicated in the pathogenesis of diverticular disease?
Definition
Increased (bowel) luminal pressure and focal weakness in the large bowel
Term
Comparing the longitudinal muscle layer of the intestinal wall from the large bowel and the small bowel, what is the key difference?
Definition
The longitudinal muscle of the large bowel is organized into three equidistant but independent bands the taenia coli, where nerves and arteries enter adjacent to the taenia coli it creates focal weakness to allow outpouchings to occur
Term
Epidemiologic studies suggest what as a cause of diverticular disease?
Definition
Western diets low in fiber and higher in processed foods, which decreases stool bulk and increases the work the muscles of the large bowel must complete to move stool along, increasing luminal pressure
Term
Diverticular disease is rare in persons <60 years old except in what acquired conditions?
Definition
Marfan's syndrome and Ehlers-Danlos syndrome
Term
When does diverticulosis become diverticulitis?
Definition
Impacted stool in the diverticula cause local ischemia and inflammation, presenting with LLQ pain, leukocytosis and fever, sometimes with frank blood in the stool, rarely the diverticula can rupture and cause hemhorrage
Term
True or false: CT scan is the gold standard of dx for diverticular disease
Definition
True, barium contrast enema can be used too but may not be as sensitive
Term
This congenital disease accounts for about 5-10% of causes of renal failure and hemodialysis
Definition
Autosomal dominant polycystic kidney disease, AD inheritance with high penetrance
Term
True or false: ADPKD is almost always bilateral
Definition
True, unilateral cases may represent other diseases
Term
These genes, involved in polycystic kidney disease, have different prognostic properties depending on which mutation occurs
Definition
PKD1 and PKD2, PKD1 mutations have an average life expectancy of 53 years compared to 69 years in PKD2
Term
True or false: PKD1 encodes a large transmembrane protein without a well described function, found mostly on distal tubular cells
Definition
True
Term
This protein, implicated in ADPKD, is found in all tubular cells and outside the kidney, and is involved in controlling intracellular calcium concentration
Definition
polycystin 2, it may also form a complex with polycystin 1
Term
What are the implications of excessive intracellular calcium with regards to cell function?
Definition
Increased cellular proliferation and growth and increased intracellular volume
Term
How are cysts in ADPKD diagnosed?
Definition
MRI, bright parenchyma surrounding dark cystic fluid, reversed on T2 waiting
Term
Where else in the body do abnormalities appear with ADPKD?
Definition
Berry aneurysms in brain, diverticula in the colon, hepatic cysts
Term
True or false: The vast majority of gallstones are "silent," about 80%
Definition
True, up to 20% of Americans have gall stones, common in Western developed countries
Term

Select the proper order of flow of bile:

1) Common bile duct, hepatic duct, r&l hepatic ducts, cystic duct

2)hepatic duct, cystic duct, r&l hepatic ducts, common bile duct

3)cystic duct, R&l hepatic duct, hepatic duct, common bile duct

4) r&l hepatic ducts, hepatic duct, cystic duct, common bile duct

Definition
4, the cystic and hepatic ducts fuse to form the common bile duct
Term
This type of stone accounts for 80% of all gall stones
Definition
Cholesterol stones, the other 20% are pigment stones of calcium bilirubinate or other pigment products
Term
What are some established risk factors for cholelithiasis?
Definition
Pregnancy, female over 40 years old, rapid weight loss, obesity, oral contraceptive use and Native American ancestry
Term
True or false: 25% of gallstone sufferers have a first degree relative with a similar problem
Definition
True
Term
True or false: CT scan is the gold standard of gallstone dx
Definition
False, ultrasound is effective at identifying gallstones
Term
Where does the achy epigastric pain of gallstones typically radiate?
Definition
Right shoulder and back
Term
This hormone causes the gallbladder to contract
Definition
Cholecystokinin
Term
This clinical exam technique elicits the peritonitis occuring with bacterial infection of a cholecystitis
Definition
Murphy's sign, presses the gallbladder against the inflamed peritoneum overlying the liver
Term
Why is morphine contra-indicated in pain management of acute cholecystitis?
Definition
It increases sphincter of Oddi contractility, which worsens pain of the bile duct
Term
True or false: cholecystitis can occur in the absence of stones
Definition
True, 5-10% of cholecystitis occurs without stones, often associated with infection, trauma or surgical intervention
Term
Two thirds of colorectal cancers arise from this type, beginning as benign glandular polyps and progressing to tumors
Definition
Adenoma
Term
What is the difference between the FOBT and colonoscopy/barium contrast enema?
Definition
FOBT detects early cancers that can still be treated, while endoscopic or radiologic tests can detect non-cancerous polyps that may progress to cancer
Term
When should screening for colorectal begin and end for US residents?
Definition
Begin at age 50, end at age 75
Term
What are the 5 general tissue responses to liver injury?
Definition
Necrosis->apoptosis, degeneration and intracellular accumulation, inflammation, regeneration and fibrosis
Term
Wilson disease, hemochromatosis, and fatty liver disease can lead to this type of liver injury?
Definition
Intracellular accumulation, fatty depositions can be microvesicular ( no nuclear displacement: pregnancy and valproic acid toxicity), or macrovesicular (AFLD, obesity, HCV, DM) with nuclear displacement by one large fat droplet
Term
Irregularly clumped organelles in the cytoplasm and large clear intracellular spaces are a hallmark of this type of hepatocyte degeneration (seen in alcoholic hepatitis, for instance)
Definition
Ballooning degeneration, where cholestatic injury causes "feathery degeneration," with a feathery appearance and yellow discoloration
Term
This region of liver parenchyma, adjacent to hepatic veins, is the most common site of liver necrosis due to ischemia, drug or toxic injury
Definition
Centrilobular, furthest from hepatic arteries and portal veins, poorest blood supply, zone 2 and 3 are uncommon injury sites but pre-eclampsia can cause periportal (zone 3) injury and necrosis
Term
In contrast to this type of necrosis, zonal necrosis typically occurs in the centrilobular area, furthest from the arterial blood supply making it vulnerable to ischemic injury
Definition
Diffuse necrosis, which can be located in the periportal parenchyma (interface hepatitis), contiguous hepatocyte necrosis that spans different lobules (bridging necrosis), scattered cells within a lobule (focal/spotty necrosis), and necrosis of the entire liver or entire lobules (massive/submassive necrosis)
Term
Ballooning degeneration can lead to this type of necrosis from cell swelling and lysis
Definition
lytic necrosis
Term
Describe the pathologic appearance of apoptotic hepatocyte death
Definition
Shrunken, pyknotic, eosinophilic hepatocytes with fragmented nuclei
Term
What three routes can lead to inflammation of liver parenchyma (hepatitis)? 
Definition
Direct toxic injury, ischemia, and CD8+ mediated hepatocyte destruction with scavenger macrophage recruitment, all processes increase number of inflammatory immune cells and cytokines present in liver, can be acute or chronic
Term
True or false: as long as the connective tissue structure of the liver is intact, the liver can recover from any parenchymal injury or biliary obstruction
Definition
True, exceptions are severe cirrhosis where CT framework is destroyed or fulminant liver disease
Term
Though inflammation and toxic injury can cause necrosis in the liver, what process involves the deposition of collagen in the liver tissue, changing blood flow and hepatocyte perfusion?
Definition
Fibrosis
Term
What is liver cirrhosis?
Definition
The sequestration of proliferating hepatocytes into nodules surrounded by scar tissue (collagen)
Term
What are some characteristic signs of liver dysfunction?
Definition
Jaundice, hypoalbunimeia, hyperammonemia, hypoglycemia, spider angiomata, palmar erythema, hypogonadism, gynecomastia, weight loss and wasting
Term
True or false: In the West, the most common cause of cirrhosis is chronic viral hepatitis
Definition
False, EtOH abuse, followed by viral hepatitis or biliary disease, unknown etiologies or metabolic diseases like Wilson, hemachromatosis, others
Term
Other than nodules surrounded by collagen, what are two pathologic features of cirrhosis?
Definition
Bridging fibrous septae linking portal tracts to one another and hepatic veins, also re-organization of vascular architecture that bypass hepatocytes and formation of anastomses between portal and caval circulation
Term
These cells secrete the collagen that builds up in cirrhosis, and are stimulated by cytokines from Kuppfer cells, endothelial cells, hepatocytes and bile duct epithelium, as well as non-inflammatory triggers
Definition
Perisinusoidal stellate cells, differentiate to form myofibroblasts and divide rapidly, increasing the synthesis of EC matrix and connective tissue fibers
Term
Macrophages in this immune tissue degrade hemoglobin into globin and heme
Definition
Reticuloendothelial system
Term
The component parts of heme include ferric iron and this structure, a four-pyrrole straight chain
Definition
Biliverdin, is reduced to bilirubin in the blood (free/unconjugated bilirubin) which binds with albumin in the blood
Term
In the hepatocytes, bilirubin typically joins with what two organic compounds to become "conjugated"?
Definition
Glucuronic acid, 80% and sulfate, 10%.
Term
Most bile is excreted in the (), in the form of urobilinogen
Definition
feces, some is re-absorbed in the gut and re-excreted by the liver, while about 5% of urobilinogen leaves in the urine
Term
True or false: Urobilin is urobilinogen in urine, while stercobilin is urobilinogen in stool
Definition
True, they are both oxidized but differently, giving urine its characteristic color and stool its characteristic color
Term
At what level of serum bilirubin does jaundice  become apparent?
Definition
1.5 mg/dl, or three times the normal level
Term
What two pathways lead to jaundice, primarily?
Definition
Hemolysis or biliary obstruction/hepatocyte damage, the former elevating unconjugated bilirubin in the blood with the latter decreasing bilirubin excretion into the gut (post conjugation)
Term
True or false: Presence of antiHAV-IgG is indicative of chronic HAV infection
Definition
False, there is no chronic carriage of HAV, IgG indicates immunity from past infxn or immunization
Term
What is the characteristic pattern of liver aminotransferase elevation in viral hepatitis?
Definition
ALT>AST
Term
After calculating an anion gap, and finding it to be elevated, what is the next step in eliciting the source of the acid-base disturbance?
Definition
gap-gap, the difference in HCO3 should equal the elevation in the anion gap, if it is larger then it suggests a super-imposed acidosis
Term
True or false: autoimmune hepatitis (AIH) is frequently associated with other autoimmune diseases like thyroid, rheumatoid and UC
Definition
True
Term
True or false: Type 1 AIH patients have serum positive for ANA and ASMA (smooth muscle), while Type 2 AIH patients have anti-LKM1 antibodies
Definition
True, Type 2 is rare in the US, more common in Europe among young children
Term
This is the simplified explanation for the development of self-antibodies
Definition
In the thymus, MHCII-CD4 interactions are regulated such that self-reactive CD4+ cells are culled when bound to MHC II antigens, in autoimmune disease a mutation in the HLA gene disrupts this process, so MHC II-CD4 interactions of self-peptides can occur, leading to the inflammation and self-antibodies seen in autoimmune disease
Term
This pathologic finding on biopsy is a hallmark of autoimmune liver disease
Definition
Though non-specific, the presence of inflammatory cells (PMNs, lymphocytes) in the portal tracts invades the surrounding liver parenchyma leading to apoptosis of the periportal hepatocytes
Term
These two drugs are recommended in treating AIH
Definition
Prednisone (low dose) with azathioprine, 80% of patients go into remission after three years, azathioprine is a purine-analog DNA synthesis inhibitor, and works mainly by suppressing mitosis of B and T cells, significantly it depresses bone marrow fxn leading to anemia, leukopenia and thrombocytopenia
Term
What three cell types make up an oxyntic gland?
Definition
Chief (peptic) cells which secrete pepsinogen, parietal cells that secrete HCl, and mucous neck cells that secrete mucous
Term
In the parietal cells, how does the cell create the negative potential in the lumen of the gland to draw in more KCl and NaCl into the cell?
Definition
Chloride ion is pumped actively from the cell into the lumen of the canaliculus, which creates a negative charge in the cannaliculus, drawing more salt into the canaliculus
Term
() and () are actively exchanged by an ATPase in parietal cells, which in results in the replacement of potassium and sodium with hydrogen in the canaliculus, forming HCl in the lumen
Definition
Hydrogen and potassium, hydrogen is exchanged in the lumen for potassium, and a separate sodium pump moves sodium back into the cell from the lumen to help form hydrochloric acid
Term
True or false: Water is pumped actively into parietal cells of the stomach
Definition
False, the water moves by osmosis following the ions moving into the cell, the final HCl concentration is about 150 mEq/L, with a pH of 0.8, this process requires about 1500 calories per liter of gastric juice
Term
True or false: pyloric glands secrete pepsin
Definition
True, pepsin is secreted by the pyloric glands as pepsinogen, which is cleaved by HCl to pepsin, it is only active at a pH of about 1.8-3.5
Term
In addition to HCl, parietal cells secrete this substance necessary for B12 absorption. Chronic gastritis can interrupt this process causing pernicious anemia
Definition
Intrinsic factor
Term
What two substances do the pyloric glands primarily secrete?
Definition
Gastrin and mucous to protect the stomach mucosa
Term
These cells secrete a very viscid mucous, alkaline, that protects the mucosal lining of the stomach from the acidic environment of the interior
Definition
Surface mucous cells
Term
These cells are the only ones that secrete HCl
Definition
Parietal cells
Term
These cells secrete histamine in the stomach, stimulating HCl secretion by neighboring parietal cells
Definition
Entero-chromaffin like cells (ECL)
Term
True or false: the most important stimulator of histamine release from ECL cells is gastrin
Definition
True, gastrin is secreted by endocrine cells in the antrum of the stomach in response to increased numbers of proteins being digested in the stomach
Term
In addition to gastrin, ECL cells can be stimulated by () from the () nerve
Definition
Acetylcholine, vagus nerve
Term
Gastrin is secreted by () cells in the () glands, and is composed of two types, G34 and G17
Definition
gastrin cells or G cells, pyloric glands
Term
Pepsinogen secretion can be stimulated by acetylcholine release from () nerve or ()
Definition
Vagus, enteric nervous plexus, acid can also stimulate pepsinogen secretion
Term
In this phase of gastric secretion, appetite centers in the amygdyla and hypothalamus elicit a signal to the motor nuclei of the origin of the vagus nerve, which then stimulates gastrin secretion and histamine secretion in the stomach
Definition
Cephalic phase
Term
This phase occurs once food enters the stomach, stimulated by vagovagal reflexes and local enteric nervous plexus signals, accounting for about 70% of gastric secretions
Definition
Gastric phase
Term
These substances can be secreted by the intestine in response to small bowel distention from food
Definition
Secretin, vasoactive intestinal peptide and somatostatin, which all inhibit gastric secretions
Term
Elimination of this organism is the most effective treatment for PUD, with a recurrence rate of PUD of 10-15% compared to 60-100% with anti-secretory therapy
Definition
H.pylori, a gram negative rod
Term
These substance, used in therapy for PUD, don't neutralize acid but increase the synthesis of mucus, preventing acid diffusion into the mucosa
Definition
Bismuth salts (pepto-bismol)
Term
Binding of this substance inhibits adenylyl cyclase and the synthesis of cAMP, working in opposition to histamine
Definition
PGE2, prostaglandin E2
Term
True or false: H2 blockers like cimetidine distribute widely in body tissues including breast milk and the placenta
Definition
True, cimetidine specifically is metabolized by microsomal oxygenase systems in the liver, and inhibits P450 cytochrome which potentiates the effects of drugs metabolized by these enzymes
Term
These drugs inhibit the K/H pump in parietal cells, irreversibly binding to the active site of the ATPase and preventing HCl formation
Definition
PPI, proton-pump inhibitors, more effective in treating PUD
Term
When is the best time to take a PPI?
Definition
30 mins before breakfast or largest meal of the day
Term
What are some possible side fx of PPI use?
Definition
Bacterial overgrowth of the small bowel, animal models suggest increased risk of gastric carcinoid tumors but not in humans, low B12, omeprazole inhibits warfarin, phenytoin, diaepam and cyclosporine metabolism but not the other PPI
Term
This drug, a less effective tx for PUD, stimulates uterine contractions and is contraindicated during pregnancy
Definition
Misoprostol, usually used as prophylaxis for PUD caused principally by NSAID use
Term
T or F: IBD is the result of an inappropriate response to normal gut microbial flora
Definition
True, pathogenesis involves the failure of immune regulation, genetic suceptibility and envioronmental triggers
Term
T or F: IBD exhibits Mendelian inheritance patterns
Definition
False, the disease is a complex multigenic trait and is not inherited in Mendelian fashion
Term
This gene, whose product is important for recognizing normal flora by binding microbes in the guy, is implicated in the etiology of what IBD?
Definition
NOD2, Crohn's Disease
Term
T or F: In both UC and CD the prime culprits for pathogenesis appear to be CD4+ T cells and injury is a result of T cells and their products
Definition
True
Term
T or F: CD is mediated by increased TH2 activation though IL4 has not been demonstrated in even though it's the usual signaling molecule for TH2
Definition
False, UC has this characteristic, CD exhibits characteristic Th1 response to IFN-y
Term
What 3 pathologic classifications define Crohn's disease as compared to UC?
Definition
Sharply delimited and typically transmural involvement of the bowel by an inflammatory process with mucosal damage, presence of noncaseating granulomas and fissuring with formation of fistulae
Term
T or F: The incidence of Crohn disease in the US is around 30/100,000 yearly
Definition
False, 3/100,000
Term
T or F: In UC, the intestinal wall is rubbery and thick, as a consequence of edema inflammation fibrosis and hypertrophy of the muscularis layer
Definition
False, that describes Crohn disease
Term
What term is used to describe sharp demarcation of diseased bowel segments from adjacent uninvolved bowel
Definition
Skip lesions, seen in Crohn disease
Term
Neutrophilic invasion of the crypts in Crohn typicall result in formation of these, which destroy the crypt
Definition
Crypt abscesses
Term
T or F: Ulceration is the usual outcome of severe active Crohn disease
Definition
True
Term
T or F: The clinical manifestions of Crohn are extremely variable and usually more subtle than UC
Definition
True, including mild diarrhea, fever and abdominal pain with interceding asymptomatic periods lasting weeks-months
Term
T or F: Fecal blood loss in Crohn can lead to anemia over time
Definition
True
Term
T or F: Extensive involvement of the proximal jejeunum causes marked loss of albumin (protein losing enteropathy) generalized malabsorption and specific malabsorption of B12, and steatorrhea due to poor absorption of bile salts
Definition
False, involvement of the terminal ileum causes these problems, though protein losing enteropathy and poor bile salt absorption can occur anywhere
Term
T or F: Crohn disease confers a 20-30 fold increased risk of colorectal cancer over the lifetime
Definition
False, 5-6 fold risk of GI tract cancer
Term
T or F: In contrast to Crohn's disease, UC spares the rectum and extends distally from the ileum
Definition
False, extends proximally from the rectum without granulomata
Term
T or F: Crohn disease is slightly more common than UC
Definition
False, UC has an annual incidence of 4-12/100,000
Term
T or F: Pancolitis describes the pattern of UC as it extends from the rectum to span the entire colon
Definition
True
Term
T or F: UC can lead to ulcerations in the mucosa of the colon, giving rise to pseudopolyps made up of regenerating mucosa
Definition
True
Term
T or F: Only in the most severe cases of UC or CD does toxic damage to the muscularis propria and neural plexus lead to complete shutdown of NM function, the colon progressively swells and becomes gangrenous leading to TOXIC MEGACOLON
Definition
True
Term
T or F: Non-specific changes in UC is the spectrum of epithelial changes signifying dysplasia and the progression to frank carcinoma
Definition
False, Particularly significant changes include all of the above
Term
Which disease presents as follows: bloody mucoid diarrhea that may persist for days weeks or months and then subside, recurring after an asymptomatic period of months, years or decades
Definition
Ulcerative colitis
Term
T or F: The associated carcinomas are often infiltrative without obvious exophytic masses, further underscoring the importance of early diagnosis in UC
Definition
True, risk of colon cancer is very high in UC
Term
T or F: In contrast to UC, Crohn disease exhibits early stricture formation but mild lymphoid aggregation and fibrosis
Definition
False, lots of lymphoid aggregates and fibrosis
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