Flashcards in UWorld - GI and Hepatobiliary Deck (157):
Phosphatidylcholine levels releation to cholesterol gallstones?
Risk INC w/ cholesterolDEC w/ phosphatidylcholine and bile salts.
Rare limiting step of bile acid synth?
Creation of cholesterol 7a hydroxylase
Presentation of colon CA based off right or left side?
Left side - obstructionRight side - systemic symptoms, symptoms of iron def anemia (fatigue). Also perhaps blood. THis is because right colon has larger caliber than left so you dont get obstruction.
What tissue can be found in Meckes?
Ectopic tissue. Gastric mucosa found in 80% of symptomatic Meckes. Acid production lead to ulceration and bleeding. Also called heterotopy. It is not metaplasia, as it was always this way. Ectopia is result of congenital malformation.
Secretory IgA - how is it produced?
Made my plasma cells. But "secretory piece" is synthesized by epithelial cells. Connects the IgAs. IgA composed of 2 Ig, J chain, and Secretory piece.
What titers do you see in pt who has been vaccinated agaisnt HBV?
HBsAg negativeAnti-HBsAgHBsAg - first viral marker - precedes aminotransferases and onset of clinical symptoms. Remains during entire symptomatic phase of acute Hep B. Suggests infectivity (as does HbeAg)Anti-HBs Ab- appears after successful HBV caccination or clearance of HBsAg. Detectable for life. Anti-HBc - appears after emergence of HBsAg, remains detectable for long after recovery\. Both IgM and IgG response. However, IgM anti-HBc presnt in "window period" - Important for diagnosis when HBsAg has been cleared and anti-Hbs Ab is not yet detectable. IgM anti-HBc is the MOST SPECIFIC marker for diagnosis of acute hept B. HBeAg - appears shortly after apperance of HBsAg - indicates active viral replication and infectivity. Disappears before hBsAg is eliminated. If it persists more than 3 months - INC risk of chronic hep B. Anti-HBe Ab- suggests cessation of active viral replication and low infectivity.
How is BUN affected in hepatic dysfunction (alcoholic etc).What triggers hepatoencephalopathy?
BUN is INC in kidney failure, HF, and dehydration.BUN is DEC in liver failure because ammonium cannot be converted to urea (BUN)So Ammonium is INC, but BUt is DEC. Ammonium enters circulation through GI tract during enterocytic catabolism of glutamine and bacterial catabolism in the colon. Enters through portal vein. If liver is damaged, ammonia instead accumulates int he blood as hepatoctes dysfunction and shunting of blood through collateral ciruclation may occur.Hepatoencephalopathy triggered by GI bleeding (and corresponding INC in ammonia and nitrogen absorption in gut). Can be triggered by anything that alters ammonia balance. Hypovolemia, , hypokalemia, metabolic alkalosis, hypoxia, sedative use, hypoglycemia, infection.
What is the mech of Vanc resistance in VRE?
D-ala D ala ->D-ala D lactate
What is the mech of N acetyl cystein in acetaminophen intox?
Provides sulfhydryl groupsActs as glutathionine substitute and binds toxic metabolites.Acetamenophen tox and p450 metabolism creates Nacetyl-p-benzoquinoneime (NAPQI). This is metabolized by hepatic glutathione. In tox, sulfation and glucuronide conjugation are saturaetd. Excess NAPQIformed form P450 -> glutathione depleted -> hepatotox.
Hyperammonemia in hepatic encephalopathy results ind epletion of what protein/carb?
Hyperammonemia -. Depletion of a-KG. Which inhibits Krebs cycle. Excess ammonia also depletes glutamate (Excitatory neurotransmitter). Causes accumulation of glutamine -> astrocyte swelling and dysfunction. AKA hepatoecenphalopathy caused by astrocye and neuron dysfunction.
What is the glutamate glutamine cycle?
Glutamate released by neurons for neurotransmissions.GLutamate taken up by astrocytes and gonverted to glutamine (non-neuroactive). Glutamine released by astroyes and taken up by neurons. Converted back to glutamate or transaminated to a-KG to be used in Krebs cycle.
Polysaccharide accumulation in lyososmal vesicles. Hepatomegaly, cardiomegaly, macroglossia, Hypotonia, MR. THink?
T2 Glycogen storage disease. Pompes diseasePolysacch accumulation was glycogen.Normal glycogen structure, but 1,4 glycosidic bonds cant be broken. Due to lack of lysosomal a- glucosidase.Glycogen accmulation in lysoosmal vacuoles is NOT seen in other glyocgen storage isease.
Adenoma to CA sequence. Go.
APC inactivationMethylation abnormalities,COX2 OVER-expressionKRasDCCP53
What GI microbio illnesses only require a few cells?
Entamoeba histolytica - just 1Giardia lamblia - just 1Shigella - 10Campylobacter jejunia 500Clostridium - 500Cholera 10^6Salmonella - 10^7Enterotoxigenic E Coli 10^9
What matenral marker indicates high probability of vertical transmission (90%) - in HBV?
HBeAg. Newborns w/ mothers o active hep B are passively immunized w/ Hep B IG. Followed by active immunization w/ recombinant HBV vaccine.
How do positive predictive value and negative predictive value relate to population sizes?
Both vary w/ population.PPV - INC when disease is more common. Probability is higher that a person who tests positive will ahve the disease in a high prevalence location. If relatively uncommon, then lower PPV.Negative predicitve value has inverse assoc w/ prevalence. As prevalence INC, negative predictive value DEC.
What stimus secretion of Bicarb? Trypsinogen?
Secretin -> BicarbCCK -> Trypsinogen (+ others. Gets pancreas and bile duct going!)
Tubular adenomaVillous AdenomaDescribe. More than just malignancy potential
Tubular - smaller and pedunculated.Villous - larger. Can have velvety or cauliflower like projections (partial obstruction)VIllous can secrete large amount of mucus -> secretory diarrhea.
Likely intestinal Carcinoid tumor location?
Appendix, ileum, rectum. Flushing,WheezingVascular telangiectasiasDIarrhea
Normal intestinal mucosal architecture, w/ tips of villi enterocytes contianing clear/foamy cytoplasm? Inheritance.
Abetalipoproteinemia - AR - impaired formation of Apo-B. Loss of function in MTP gene. Manifests in first year of life - foul smelling, greasy stools. low plasma triglyeride and choletserol levels. Fat soluble vitamin def. Acanthocytes. Neuro symptoms (progressive ataxia, retinitis pigmentosa)
Best way to detect C diff colitis
PCR detection of Toxin A and B genes in stool.
Retroperitoneal hematoma w/ mild ab pain after MVA. Think?
Pancreas. Damage to transverse colon, liver, and spleen would NOT cause retroperitoneal hematoma. They are INTRAPERITONEAL organs. Dmg to any of these would lead to hemoperitoneum - free blood in peritoneal psace. NOT retroperitoneal.
What is the mech of H pylori damage -> ulcers? Wher does it occur?
H pylori damages the somatostatin producing antral cells. Somatostatin inhibits gastrin release. So High gastrin levels -> acid. Not neutralized by bicarb -> duodenal ulcerations.H pylori in gastric antrum and fundus,as well as any ectopic tissue, but does not seem to invade these. Mainly somatostain producing antral cells.
What enzyme allows for glucose synth out of triglyercide breakdown rpoducts?
Glycerol kinase.Triglycerise -> Glyerol + Fatty Acids (Acety Coa -> beta ox/ketogenesis)Only Glyerol can be used for gluconeogenesis. Glycerol + Glycerol kinase -> Glycerol 3 phosphate.
Where is the pancreas derived form?Describe embryology of normal pancreas devo as well as annular pancreas devo.
ForegutVentral pancreatic bud (Attached to gallstone) + DOrsal pancreatic bud. Ventral rotates posteriorly so that gallbladder is now behding duodenum. Ventral and dorsal pancreatic buds fuse. If the ventral bud cleaves into two parts and orms a ring -> annular pancreas. Cna cause dudoenal stenosis (bilious vomiting)Incomplete fusion of ventrla and dorsal pancreatic buds would lead to pancreas divisum -> usu asymptomatic.
Where do most viruses get their plasma membrane (Envelop from?) What is the exception?
Most enveloped acquired lipid bilayer from budding through plasma membrane.Exceptions include Herpes virus - bud through and acquire hot cell nuclear membrane.
Cricopharyngeal dysfunction causes?
High dysphagia - difficulty swallowing - felt at throat - coughing, chocking. Zenker diverticulum can form. May also ead to food aspiration. Diverticulum may be palpated as LATERAL neck mass.
when do you see true divertula of esophagus vs fake?
Fake - Zenker - cricopharyngeal muscle dysfunction (= diminished relaxation -> INC inraluminal pressure -> herniation). True - scarring and traction - seen in mid portion - may result from mediastinal lymphadenitis (TB
Elevated Alk phosph of unclear etiology. What is next?
Elvated alk phos could be Liver, Bone >> Intestine, kidney, placenta, leukocytes, neoplasmsNext step should be hepatic GGT (predominantly hepatocytes and biliary epithelia). Useful in determining whether elevated alk phosphatase is hepatic or bony origins.
Diarrhea and constipation w/ draining fistula near coccyx?
Crohns.You can have fistulas anywhere - skin (perianal fistula), urinary bladder, vagina, retroperitoneum, oral apthous ulcers.
Hepatic vs Renal clearance. WHat characteristics favor eac?
Hepatic - high lipophilicity and high volume of distribution, high penetration into CNS. THese qualities make it so that drugs will be filtered, but will be easily be able to be re-enter tissues from tubules. SImilar to how charged and uncharged pass though kidney membrane. However, charged are stuck.
What cell cannot use ketone bodies?
Erythrocytes (lack mito)Hepatocytes as well - do have mito, but lack enzyme succinyl CoA acetoacetate CoA transferase (thiophorase) - CANT use ketones.
What ab organ is not from a foregut derivative, but is supplied by the foregut artery?
Spleen - derived from mesodermal dorsal mesentary - supplied by celiac.
How does urea breath test work?
Give Carbon radiolabeled urea orally. H pylori ureas breaks down urea into carbon dioxide and ammonia. The CO2 is absorbed into bloodstream, and exhaled in pt breath. Do breath samples 30 minutes after ingested urea.
Mech and bugs w/ IgA protease? W Protein A?
IgA protease - cleaves di-gammaglobulin IgA - prevents the prevention of entry. Found in Strep pneumo, H flu, Both NeisseriaProtein A - has higher affinity for IgG than IgG does to bacteria. Binds IgG and prevents it from opsonizing Staph A.
Opioid analgeis can lead to what very rare side effect?
SHould know that common side effect is constipation. Contraction of smooth muscle cells in sphincter of Oddi can lead to constriction and spasm -> INC bile duct pressure - > Biliary colic. Severe cramping and pain in right upper abdomen.
Hepatic abscess - common causes?
Enteric bacteria via ascending biliary tractStaph A - hematogenous seeding to liver.
Told that wife and child are Jehovas witness by husband and not to give blood. Cant get into contact w/ husband, no Jehovas card. What to do?
Give blood - standard of care. No outline, and no contact.If dad was back in contact during the final moments and still said no blood - there would be no blood. This is because some jehovas witness will be okay with life saving treatment.
Why is Hep D defective?
Must be coated by external coat antigen of HBsAg before it can infect hepatocytes and mutlple.
Erosions vs Ulcers ?
Erosions - may not past through mucosa. Do not go past muscularis mucosa (which is in between mucosa and submucosa)Ulcers past mucosa into submucosa.
Common causes of SMA syndrome?
Dimished mesenteric fat that provides a buffer - low body weight, recentlw eight loss, severe burns, prolonged bed rest. Lordosis. Also Surgical correction of scolioisis, which lengthens spine and DEC mobility of SMA> Traps the TRANSVERE part of duodenum.
HIV pt w/ esophageal pain. 3 Major possible endoscopic findings?
Candida - patches of grey/whtei psuedomembranes.HSV1 - small vesicels that evolve into "punched out" ulcers. - EOsinophili intranuclear inclusions (Cowdry type A) in multinuclear squamous cells .CMV - Linea ulcerations - both inranuclear and cytoplasmic inclusions.
What is hyperestrinism in alcoholic cirrhosis due to? 2 things
DEC catabolism of estrogenINC sex hormone (Testosterone) binding globulin. (DEC free testosterone to estrogen ration)Leads to gynecomastia, testicular atrohy, DEC body hair, spider angiomata
Words associated w/ diverticula?
Pulsion. (Opposite of suction) DUe to INC intralumina pressure during straining/constipation.
Where does lipid absorption occur? Where does lipid digestion occur?
DUodenumo - digestion of lipidJejunum -Absorption of lipidIleum - sight of Bile B12 absorption.
Major effect of cholecystectomy on bile flow?
Cholecystectomy has little effect on secretion and absorption of bile. Change is the RATE. With surgery it is constantly released, as there is no storage place.Pt w/ cholecystectomy are less able to tolerate large fatty meals in one sitting - unable to release a large coordinated amount.
When do you use double stranded DNA probe?
Southwestern blot. Looking for DNA BINDING PROTEINS! Such as c-Jun and c-Fos (DNA binding protein).
What is important about the 16S rRNA sequence
Essential for initiation of protein synthesis - contains sequence complementary to SHine Dalgarnoa sequence on mRNA. (Shine Dalgarnoa sequence is located 10 bases upstreak of the AUG start codon on prokaryotic mRNA)So the 16S subunit of 30S ribosome allows for the binding of the mRNA
What is another name for Lactose?How can lactase def present acutely?
Galactosyl B-1, 4 glucose.After viral gastroenteritis that damges intestinal epithelium. Causes ab distention, flatulence, diarrhea after lactose ingestion
Another name for Shiga like toin? Mech?
Shiga = Vero cytotoxin.Inhibit protein synth B - forms pentamers w/ central pore.A - activates catalyses that remove single specific adenine residue -> prevent binding of tRNA to 60S subunit and prevent protein synth.
How does halothane/inhalte anesthetic hepatotoxicity present?How do the signs/labs differ from end stage liver disease (cirrhosis)
Anytime SURGERY and LIVER are involved, consider this. Rapid atrophy -> shrunken. Cannot be histologically distinguished from acute viral hepatitis (widespread centrilobular hepatocellular necrosis and inflammation of portal tracts and parenchyma)Significant elevated aminotransferase levels, INC prothrombin time (PT - F7) - Eosinophilia. Normal albumin levels (half life of 20 days - acute doesnt get to this)Cirrhosis - DEC albumin level due to chronic process - palmar erythema and ab distention w/ ascites. May see splenomegaly from portal hypertension from cirrhosis (would not see in acute setting)
Why do IgGs agaisnt Hep C envelop not confer immnity?
Envelopes are HIGHLY immunogenic.BUUUUUUUUUUUUTTTTVARIETY of antigenic structures of hep C virus envelop proteins. Host Ab lags behind produciton of NEW mutatn starins of HCV. Immunity is not conferred.No 3->5 proofreading built in -> hypervariable .
Salmonella enteritidis (vs Shigella)vsSalmonella Typhi?
Enteritidis - - MANY ANIMAL RESERVOIRS - Dissemiantes hematogenously (sickle cell osteomyelitis), Produces Hydrogen sulfide. Invates and causes monocytic response (eyers patch) + in blood and stool cultures.Shigella (No hydrogen sulfide invades - causes PMN rx. .Typhi - typhoid fever - HUMANS ONLY. rose spots on ab, FEVER, heardache, diarrhea. May remain in gallbladder and cause carrier/chronic state.
Mech diff between cause of HCC w/ Hep B and Hep C?
Hep B - integrates w/ host genome. Codes for HBx protein - substance the distrupts growth control of infected cells by activating multiple growth promoting genes. HBx also binds to p53. Hep C - chronic inflam.
Where is colon adenoA most likely to occur?
Rectosigmoid colon. Rarely Transverse and descending. So "left side obstructs is referring to rectosigmoid" Although left side is smaller, the lumen is smaller.Ascending colon is second most common location of colorectal CA. Right side (Ascending) are large, bulky masses - more likely to bleed.
What is ELISA good for measuring?
Enzym linked immunosorbent assay - commonly sued to measure protein in body fluid - for example - to measure plasma insulin levels
Go deep into the mech of hemochromatosis (genetic)
AR - HFE chr 6. Due to impaired HFE protein expression on basolateral surface of epithelial cell in small intestine crypts.HFE complexes w/ B2 microglobulin to bin to transferrin receptor. HFE usu binds to Transferrin receptor to regulate Iron endocytosis.PT w/ HFE mutation are unable to bind to transferrin receptor - no regulation.
Tx for Hep C? Mech?
INFa and Ribavarin.INFa = immuno stuff.Ribavarin - prevents DNA replication - multifactorial.Ribavarin - Nucleoside Antimetabolite - interferes w/ duplication of viral genetic material. 1. Induces lethal hypermutation2. Inhibits RNA polymerase and inhibits Inosine monophosphate dehdrogenase (Delets GTP)3. Causes defective 5' cap formation in viral mRNA 4. Modulates a more effective immune response. RIBAVARIN CAN WORK AGINAST A NUMBER OF DNA AND RNA VIRUSES. Currently used for Chronic Hep C and RSV>
Wwater born gastroenteritis - bacteria - able to survive in ALKALINE MEDIA. Think? STool microscopy?
VIBRIO. Noninvasive - mucus and epithelial cells only.Vibrio is INCREDIBLY acid sensitive - this is why you need to inest 10^10 V cholera for them to grow! Or 10^6 if Vibrio is in food (food buffers) So Vibrio more common in Achlorhydria states.
Different Mech of APC vs Microsatellite?
APC - needed for intercellular attachmentLynch (HNPCC) - DNA mismatch repair. - PROXIMAL COLON ALAYS INVOVLED. Also, has TENDENCY FOR EXTRAINTESTINAL MALIGNANCIES.
Location of FAP, HNPCC, Sporadic
FAP - pancolonic - always involves rectum.Sporadic - (adenoma -> Ca sequence) - APC, Kras, P53/DCC- Left sided (Rectosigmoid>ascending>> others)HNPCC - Proximal/Right colon always involved.
Estrogens effect on choletserol?
Estrogen INC biosynh of cholesterol by INC hepatic HMG-CoA reductase activity. Suppression of cholesterol 7a-hydroxylase (by fibrates) - DEC the conversion of cholesterol to bile acids. Results in Excess cholesterol (stones)
What are the cause of Pigmented gallstones?
Black (radioopaque)= HemolysisBrown (radiolucent) = Infection Typically arise secondary to infection in biliary tract. More common in Asia. DUe to release of B-GLUCURONIDASE by injured hepatocytes and bacteria. This enzyme contributes to hydrolysis of bilirubin glucuronides and INC UCB in bile.
What would predispose one to chronic giardia infection?
Cystic lesions following binge drinking. Think?What lines the cyst?
Pseudocyst!Fibrous and granulation tissue.Unlike true cysts, they are NOT lined by epithelium.Aka true cysts are lined by epithelium!
What stains positive for periodic acid Schiff stain? (PAS?)
Detects polysacchsGlycogen storage diseaseAdenoCA (often secrete neutral mucinsPagets disease of Breast,A1AT DMycosis fungoises, SezaryFungal
Primary Biliary Cirrhosis.
Progression of alcoholic cirrhosis?Greatest prognostic factor in cirrhosis?
Alcoholic steatosis (Reversible) ->Alcoholic hepatitis (reverisble) -> Cirrhosis (irreversible)Must test intrinsic protein making abilities. Serum albumin and Prothrombin time (factors) are greatest prognostically (over AST, GGT, Prolonged bleeding time etc)
Cause of green vomitus in 2 year old w/ absence of small bowel and distal ileum seen windinw around thin vascular stalk?
After duodenum (congenital malformation), Jejunal, ileal, and colonic atresia s NOT cause dby abnormal devo - they are VASCULAR ACCIDENTS IN UTERO - DEC perfusion -> ischemica -> narrowing of bowel/obliteration of lumen.What was dscribed is "apple peel" atresia - terminal ileum distal to atresia spirals around ileocolic vessel
What is acute acalculous cholecystitis? Cuases?
Acute inflam of gallbladder in ABSCENCE of gallstones - commonly seen in hospitalized and severely ill
First line therapy for pt w/ hypercholesterolemia? 2 organ systems to worry about? Monitoring?
Hepatotoxicity, Muscle toxicity.Measure LFTDiscontinue statin if ASTAT levels are 3 times upper limit of normal.
Explain pancreas divisum?
Common congenital anomaly resulting from failure of duct system to fuse.Normally, main pancreatic duct from dorsal, and ventral just forms the uncinate process.In pancreatic divisum, the "Main pancreatic duct" is now from the ventral pancreatic bud, although the dominant duct is still i nthe dorsal pancreatic bud.
Describe Hep A
Average incubation of 30 days - transmission fecal oral - due to overcrowing and poor sanitation - also contamined water/food, raw/steamed shellfish in the US. Onset is acute malaise, fatigue, anorexia, nausea, ab pain, and AVERSION TO SMOKING. Hepatomegaly common. AST and ALT spie early in illness. Anti-HAV IgM is positive and marker of active disease. Self limiting - does not progress to chronic hepatitis cirrosis or HCC. Tx is largerly supportive - complete recovery excepted in 3-6 weeks. Close contacts should be given Immune globulin.
Oysters think?Boiled eggs think?
Oysters - Hep A, VibrioBoiled Eggs - Salmonella
Describe strongyloides life style and diagnosis?
Diagnoiss- rhabditiform (noninfectious) larvae in stool.Infection begins w/ skin penetration by filariform (infectious) larva. Migrate to lungs. Are swallowed and carried to small intestine. Molt into adults, lay eggs in intstinal mucosa. Eggs hatch into noninfecitous rhabditiform larva that are excreted in stool.Rhaditiform larva molt into infectious filariform larva to attack others or back to the host!
Where is Panthothenic acid needed?
Panthothenic acid actively transproted into cell - ATP dependent phosphorylation -> tranforms into Coenzyme A.Need for Oxaloacetate to Citrate.
Location of promoters vs enchancers/repressors?
Promoters - upstream of associated genesEnancers/repressors can be ANYWHERE
What is HBsAg?
Noninfecitous glycoprotein that forms spheres an tubules 22 nm in diameter. Infected hepatocytes may secrete enormous quantities of HBsAg, often exceeding amount of HBcAg produced.
Carnitine def - see?
impaired fatty acid transport into mitochondria. REstricits ketone body production.
Aldolose B def. What to avoid.
Sucrose (Fructose + glucose)and Fructose of course.
What are anal fissues and where do the occur?
Longitudinal tear in mucosa 90% occur at the POSTERIOR midline of the anal verge. Becuase posterior is relatively poorly perfused - mucosa more senstivie to trauma by hard fecal masses - Distal to dentate line.
Why is Chrons assoc w/ oxalate kidney stones?Gallstones?
Impaired bile absorption in terminal ileum leads to bile loss in feces (AND EXCESSIVE LIPIDS) - lipids bind Calcium ions and are excereted as soap. Free oxalate (normally bound by Ca and forming unabsorbable complex) is absorbed and forms urinary calculi. See Oxalate kidney stones!AKA reduced Ca-Oxlate binding in intestines due to INC Ca-Lipid binding.So Chrons is assoced w/ kidney stones.ALSO ASSOCIATED W/ GALLSTONES. Less bile absorbed, more cholesterol around -> Choletserol precipitates.
What is N-myc?
Transcription factors. Can be detected by DNA probes.
Where should you biospy for Hirschsprungs?
Submucosa or narrow part (distal to dilated portion) - this is wher ethire is a lack of autonomic plexus.
Hepatitis w/ high incidenceo f fulminant hepatitis in pregnant women?
unevenloped RNA virus - Hep E.
Diarrhea for months - gastric contents show TOTAL LACK OF GASTRIC ACID SECRETIon. What is this and how to treat?
VIP-oma.Vasoactive intestinal peptide - pancreatic islet cell tumor that causes excessive VIP secretion -> pancreatic cholera, or WDHA syndrome (Watery Diarrhea, Hypokalemia, Achlorhydria). VIP inhibits gastric acid secretion.Tx w. somatostatin(octreotide) - inhibits VIP.
H pylori in urea test - which way does the pH go with h pylori?
Urease converts urea to carbon and ammonia (INC pH. more basic) -
Causes of acute pancreatitis other than gallstones and alcoholism (total of 80%)?
If pt has acute pancreatitis, does not drink, and does not have gallstones on ultrasound..Recent endoscopic retrograde cholangiopancreatogrpahy (ERCP)Drugs (azathioprine, sulfasalazine, furosemid,e valproic acid)Infections (mumps, coxsackie, myoplasma pneumoniae)HYPERTRIGLYCERIDEMIASurgeryHyperCaHypertriglyceridemia causes pancreatitis because normally fatty acid bound to albumin - if fatty acid exceeds binding capacity of albumin -> direct injury to pancreatic acinar cells.
Where are parietal cells located, where are Chief glands located (histologic cross section)
Parietal - superficial region of glandsChief cells - deeper region of gastric glands.
Malabsorption break down - First screening test for malabsorption?
Pancreatic exocrine insuff (CF, chronic pancreaitits)Intestinal mucosal defect (celiac, tropical sprue, whipple, Chrons other)Bacteiral prolif (complete for nutrients)FIrst test to screen for malasorption is sudan III stool stain to look for FAT in stool sample.
Which element disorder do you get DM? Which do you get brain damage. To where/what effects?
Hemochromatosis - bronze diabetes + cirrhosisWilsons Disease - basal ganglia dmg - can get parkinsonian.
Live vs killed vaccine (polio) - what differences in Ig would you see?
Live - would have mucosal IgAKilled - would not have mucosal IgA>
Appearance of gut carcinoid cells? Location
MINIMAL TO NO VARIATION IN SHAPE AND SIZE OF TUMOR CELLS. Very identical. Glands, nets, rows, sheets may be formed. Most often appear in the Ileum, Appendix, and rectum.From malignant transformation of enterochromaffin (endocrine) cells. They may contain secretory granules on EM (can secrete stuff)
Where is Acetyl-CoA an allosteric actovator?
With gluconeogenesis. Acts by INC the activity of pyruvate carboxylase -> OAA.
What stimuli is most likely to cause parietal cell proliferation?
Gastrin. This is what we see in ZOllinger Ellison.
NADPH from HMP shunt can be used for?
CHolsterol and Fatty Acid Synthesis. Reducing glutathione.
High HBeAg with low anti-HBeAg for months. Suspect?
Chronic Hep B w/ high infectivity.
Where does Cimetidine Act?Lansoprazole?Sucralfate?
CImetidine -parietal cell H2 receptorLansoprazole - PPI (like omeprazole)Sucralfate - binds to base of mucosal ulcers - provides physical protection from acid.
Homeobox - What doe sit do?TATA box. What is the function?
DNA sequence that usu codes for DNA binding trancscription factors. Promotor region on DNA - binds transcription factors and RNA polyermase 2 during intiiation of transription. 25 bp upstream of coding region
What can oral admin of fixed fose of D-xylose be use dfor?
D xylose is a monosaccharide - does no require pancreatic enzymes to be absorbed.Use D xylose to differentiate malabsorption of pancreatse vs GI mucosal etiology.If pancreas problem, Xylose is absorbed.If GI problem, Xylose is not absorbed.
Dimple for anus (imperforated anus) assocated w/?
50% are assocated w/ urorecetal, urovesicular, urovaginal fistulas, or other GU tract malformations - renal agenesis, hypospadia, epispadia, bladder extrophy.
Kaposi sarcoma biopsy findings?
Spindle shaped tumor cells w/ small vessel proliferation
which E Coli do not ferment sorbitol? What else do they not produce? What DO they produce? What is the mec of that?
EHEC - - shiga like toxin.DO not ferment sorbitolDo not produce glucuronidaseProduce shiga like toxin - inactives 60s ribosomal subunit - inhibits protein synth.
NF-kB responsible for?
Cytokine production. Can lead to persistant chronic inflam in GI tract (Crohns) NOD2 mutation may be linked - INC acrivity of NF-kB induced inracellular microbes.
Primary mode of copper excretion?
Absrbed copper forms ceruloplasmin. THis and unabsorbed copper are secreted into BILE and excreted in stool - route for copper elimination.Iron does not have eliminatino except sloughing.
Air in gallbladder and biliary tree. Must think?
Cholycyst-enteric fistula. Fistula would allow gallstone into small bowel -> gets trapped at ileo-cecal junction. Air backflows into gallbladder. Air is NOT seen in bile duct during normal choledocolithiasis.
Histology of Viral Hepatitis?
INjury: Diffuse swelling ("ballooning degneration"). Hepatocyte Death: lobular architecture distruption and conflence hepatocyte necrosis (bridging necrosis). Mononucealr inflam in sinusoid and portal tracts.
What gene mutation is found in most cases of sporadic colon cancer (non familial)
APC. It is FIRST mutation in the adenoma -> CA seuence
How is Isoniazid Excreted?How is this related to Drug induced SLE?
Acetylation to N-acetyl isoniazid by hepatic microsomal sstemic via N-acetyl transferase -> excreted in urine.There are fast acetylators and slow acetylators. This can also be for other drugs: Sulfonamides (dapsone), hydralazine, procainamide (SLE tox!) Slow acetylators are at risk for buildup of these drugs and triggering of DILE.
Medical treatment for carcinoid before surgical resection?
Octreotide - somatostatin analogue - prevents secretions. Also used to inhibit secretory diarrhea in VIPomas (pancreatic endocrine tumors)
Postprandial ab pain - think 2 things?
Gastric Ulcer. Ischemic Mesenteritis.
Neural crest migration. Describe time in fetal development. Describe locations
Migrates caudally - wall of proximal colon at 8th week of gestation, and rectum by 12th week.Therefore, in Hirschprungs, the rectum is 100% of the time affected!The simgoid colon is 75% affected.IT HAS TO GO IN THIS PATTERN DOWNWARDS. You cannot have normal rectum w/ abnormal sigmoid colon.
Presentation of systemic mastocytosis?
Histamine! - Syncope, flushing, hypotensino, tachycardia, bronchospasm. - Skin (Pruritis, Urticaria, ) - Gastric hypersecretion! Gastric ulceration may occur.
Hep A presentation?
ASYMTOMATIC! Usually. Anicteric.Can also preset as acute, self limited illness of jaundice, malaise, dark urine, aversion to smoking.Estimated that 40-70% of US adults have anti-HAV IgG w/ most positive individuals never experiencing icteric illness.
Esophageal dysmotility is CREST is due to?
atrophy and fibrous replacement of esophageal muscles. Can lead to esophageal hypomotility and imcompentence of LES due to atrophy and fibrous replacement of muscles. DIlatation can cause reflux. and INC risk for Barretts ->
Order of enzymes in repair of cytosine deamination?
Glycosylase - creates empty (AP) siteEndonuclease - 5' cutLyase - 3' cutDNA polymeraseLigase
How is IBD associated CRC different from Sporadic CRC?
Colotis associatd CA more likley to affect:Younger ptProgress from flat and nonpolypod dysplasiaAppear mucinous/signet ring morphology (higher histological grade) Develop EARLY p53 and LATE APC mutations Be in proximal colon.Be MUTLIFOCAL in mature.
What are the changes that are seen after lactose challenge in lactose intolerant pt?
Incomplete hydrolysis of disaccharide lactose leads to osmotic diarrhea - bacteiral fermentation produces short chain fatty acids and excessive hydrogen . This hydrgen acidifies stool, and LOWER pH. Also, stool osmotic gap INC (due to poorly absorbed substances - > stool osmotic gap is large!D xylose absorption is not affected in lactose intolerance. Assoc w/ malabsorptive problems .
Coenzymes needed to turn Pyruvate into Acetyl CoA? a-KG to SUccinyl CoA?
VIa pyruvate dehydrogenaseVia a-KG dehydrogenaseSAME THINGS!Thiamine (B1)Lipoic AidCoA, FAD, NADDEF of lipoic acid can lead to lactic acidosis because TCA cycle cannot occur w/o these two things.
Amantia phalloides toxin (mushroom) - fatal doue tow hat mech
Amatoxins - bind DNA dependent RNA POL T 2 - HALTS mRNA synth! -> apoptosis. Presents w/ ab pain, vomiting, severe cholera like diarrhea, - acute hepatic and renal fialure. Urine test for a-amanitin to confirm suspected poisoning.
C perfringens?C diff toxin vs
C perfringens - lecithinase/phopsholipoase -> cleaves cell membranesC diff - Toxin A, B - cytoskeletal distruction via actin depolymerization. Test for toxin in stool.
What are the points of portosystemic anastomoses?
Portal listed firstLeft gastric vein -> Esophageal veinSUperior rectal -> Middle/Inf RectalParaumbilical veins -> Superficial/Inf epigastric
Ways to pass first pass oral first pass metabolism?
SublingualRectal (middle and inferior drain drain to systemic via inenral iliac and intenral pudendal respectivel) IVSubcutaneous
Frequent consequence of gallbladder hypomotlity? Black pigments?Brown pigments?
Hypomotility -> biliary sludge - results from bile precipitation. Is a known precursor to stone formation.Black pigments - intravascular hemolysisGrown pigments - biliary tract infection
Histology of liver in Portal Vein Thrombosis vs Budd CHiari?
Portal Vein Thrombosis - signs of portal HTN, w/ esophageal varices (+) and splenic enlargement. The liver is unaffected though. Ascites is uncommon as w/ portan vein thrombosis since sinusoidal HTN does not devo.Budd Chiari - Occlusion of hepatic vein (which drains blood from liver and portal circulation). Liver biopsy shows centrilobular coengesion and fibrosis.
Palpable nontender gallbladder? When mixed with obstructive jaundice (pruritis, dark urine, pale stools?)
Courvoisier signs (palpable but nontender gallbladder)+ obstructive jaundice -> AdenoCA at head of pancreas.
5 Signs of Lead poisoning?
Colicky ab pain "lead colick", Headache, Impaired concentrationBluish pigmentation "lead line" on gum-tooth lineWrist drop/foot drop from peripheral neropathyMicrocytic hypochromic anemia w/ baophilic strippling.
Severe pruritis (esp at night) think? + fatigue and pale stools Histological features? Hint - if they are middle aged women?Hint (if they have Sjogrens?)
Primary biliary cirrhosis. See granulomas and destruction of inerlobular bile ducts Duh! see granuloas because it is autoimmune related.
Map Kinase pathway. What energy molecule?
GTP. Growth factor ligand -> autophosphorylation of tyrosine residue -> interaction w/ SOS protein -> Ras protein w/ GTP -> Raf -> MAP kinase -> Gene transcription
Tx for arsenic poisoning?LeadMercury?Cyanide?
Dimercaprol. Has a side effect of neprhotoxicity and HTN.Lead - CaNa2EDTAMercury - CaNa2EDTA (Calcium Disodium Versenate)Amyl nitrate (methemoglobin) then thiosulflate. Also hydroxocobalamin.
Key sign of arsenic poisoning?
Garlic odor on breath.
Where is the least blood supply anastamosis in the stomach?
Short gastric, off of splenic. Vulernable to ischemic damage following splenic artery blokage.
Two common bacteria w/ prefomed toxins? Food assoc w/?
Staph A - enterotoxinpicnic/potluck -> poultry, egg, meats, potato/macaroni salad, dairyB cereus - preformed heat stable exotoxin - starchy food (rice)
Peristant jaundice beginning in 3rd to 4th week of life? Dark urine, acholic stool, COnjugated hyperbilirubinemia? Hint - inrahepatic bile duct proliferation, portal tract fibrosis/edema, parenchymal cholestasis?
Biliary atresia. Total obstruction by 3rd/4th week. Also get hematomegaly.Hemolytic disease of newborn from Rh affected infants - appears w/in 24 hours. Unconjugated hyperbilirubinemiaPhysiologic jaundice occurs w/in first 24 hours and ends by first week. (unconjugated hyperbilirubinemia)
Major side effects of proteases?
LipodystrophyHyperglycemia (insulin resistance -> DM!)Inhibit P450.
99mmTc-pertechnetate scan - What for?
Detecs presence of gastric mucosa. Accumulation of pertechnetate in RL Ab dis diagnostic of Meck diverticulum w/ ectopic gastric mucosa. Due to failure of obliteration of ompalomesenteric duct AKA VITELLINE DUCT. SAME THING.
Mutliple mases in the liver think?
Metastases. Most common malignant neoplasm of liver. 20x more common than HCC. Liver is second most common site of metastatis spread (after LN) duet os ize, dual blood supply, high perfusion rate, and filtration function of Kupffer cells.Nodes frequently outgrow their vascular supply and become centrally necrotic and umbilicated.
Prognosis and demographics of Hepatic angiosarcoma?Hepatoblastoma?HCC?
Angiosarcoma - Very poor - extremely aggressive. - Vinyl chloride, arsenic, THorotrast .Hepatoblastoma - most common liver neoplasm of children - assoc w/ FAP and beckwith Wiwdemann . uus fata if not surgically resectedHCC - older pt - can be unifocal or multifocal - or diffusely infiltrative. Hx of cirrhosis or Hep B, C infection. .
Histology of lactose intolerance pt/
Normal intestinal mucosa. Light and EM has never demonstrated identifiable abnormalities.
How can Hep B NOT be detected?
Hep B can be detected in all body fluids except stool.
Low ketone bodies after fasting. What is this likely to be what enzyme defect?
Defect w/ beta oxidation.First step is catalzyed by Acyl-CoA dehydrogenase. Most commonly deficit enzyme.
What biochem rx occur in cytoplasm?What occur in mitochondria?
Cytoplasm - all of pentose phosphate + more Mito - pyruvate carboxylase, ornithine transcarbamoylase, succinate dehdrogenase, 3 hydroxy3methyglutaryl CoA (HMG CoA) lyase - . B oxidation, ketogenesis, TCA
How does Shigella invade?
First gainst access to M cells in Peyers patch in ileum through ENDOCYTOSIS. Then, lyses the endosomes and spreads laterally.
Main mech of glucose-induced inhibition of lac operon?
Depletion of cAMPGlucose DEC adenlyate cyclase -> low cAMP. Low cAMP -> DEC expression of genes on lac operon.
Ways to inactivate HepA?
Water chlorination, bleach (1:100 dilation), formalin, UV irradiation, boiling to 85 degrees for one minute. NOT by acid! It is fecal-oral so it can take acid!Also HAV does not have an envelop - so tx w/ diethyl ether does nothing. Envelop is sensitive to ether.
How does HBV lead to HCC?
HBV integrates - viral protein HBx activates synth of Insulin like growth factor 2 and receptors for ILGF1 -> stim cell proliferation! Also suppresses p53.
Fatigue and weight loss - fine eosinophilic protein granules inside of hepatocytes?
Hep B.Eosinophilic protein granules instide of hepatocyte cytoplasm etc are HBsAg spherules and tubules. Commonly described as "ground glass"
Ab distention in Ulcerative Colitis. Be wary of? First test?
Toxic megacolon. Plain ab X ray. Barium constrast and colonoscopy contraindicated due to risk of perforation. Ab ultrasound is not useful for diagnosis of toxic megacolon.
Most common benign liver tumor? Describe histo?
Cavernous hemangioma - most comon benign liver tumor.Microscopically, cavernous blood filled vascular spaces . Biopsy is NOT recommended as procedure may cause fatal hemorhage and is of low diagnostic yield. May be single or multiple - well circumscribed masses of spongy consistency. Prognosis excellent - surgical resection option for those who are symptomatic/compression etc.
2 most common causes of acute pancreatitis?
Alcohol, Gallstones.W/ alcohol can see macrocytosis! Can be independent of folate/cobalamin def.
What test is most helpful in diagnosisng acute cholecystitis?
Acute cholecystitis is secondary to gallstone formation in 90% of cases.use radionuclide biliary scan (HIDA scan).Give Radionuclide. It is taken p by liver, and excreted into common bile duct.If it is seen in common bile duct and proximal bowel (BUT NOT IN GALLBLADDER) suggests blockage! and tehrefore direct flow from liver into small intestine)AKA gallbladder is NOT visualized in HIDA>
How does HBV damage hepatocytes.
Does not diretl dmg.Viral HBsAg and HbcAg are expressed on MHC 1 -> CD8+ destroyes infected hepatocytes
What can see on Dubin Johnson histo (not gross histo -> black)
Histo - Dense pigments composed of epinephrine metabolies within lysosomes
What determines malignancy potential of adenomatous polyps?
HistologyDysplasiaSize (less than 1cm - unlikely , greater than 4cm 40% risk of malignancy
What stains PAS w/ tropheryma whippelli? What color?
Deep magenta - stain of glycoprotein in cell walls of actinomycete tropheryma.
Most common cause of acute viral hepatitis in young adults?What do you see on histo of acute viral hepatitis?
HAV. Esp as there are endemic areas in the world. Diffuse balloning degeration (hepatocyte swelling), mononuclear cell infilrtrates, Councilman bodies (eosinophilic, ACIDOPHLIC bodies, apoptotic hepatoctes)