Looking at all age groups, what is the most common cause of viral enteritis?
Norwalk
Among infants and young children, what is the most common cause of severe diarrhea?
Rotovirus
What micro-organism causes “picnic food poisoning”?
Staphylococcus aureus
What microorganism that causes food poisoning is associated with Chinese food?
Bacillus cereus
What microorganism that causes food poisoning is associated with saltwater crabs and shrimp?
Vibrio (cholera and non-cholera)
What microorganism that causes food poisoning is associated with improperly prepared home canned fruits and vegetables?
Clostridium botulinum
What microorganism is the number one cause of foodborne illness in the U.S.? Second?
1st: Norovirus
2nd: Salmonella
What microorganism causes bloody diarrhea?
Campylobacter
What are toxins associated with gram-negative bacteria that are usually released after lysis of the bacteria?
Endotoxins
What are chromosomally encoded exotoxins that are produced and secreted by several bacterial organisms?
Enterotoxins
Enterotoxins are often heat-stable and frequently cytotoxic, killings cells by doing what?
Altering the apical membrane permeability of the mucosal cells of the intestinal wall
What may be secreted or, similar to endotoxins, may be released during lysis of the cell?
Exotoxins
What destroys most exotoxins?
Heating
What are two common exotoxins?
Botulinum
Corynebacterium diphtheriae
What condition is primarily seen in premature infants, where portions of the bowel undergo necrosis?
Necrotizing enterocolitis
What illness is characterized by offensive smelling diarrhea, fever, and abdominal pain?
Pseudomembranous enterocolitis
What is a cause of antibiotic-associated diarrhea that is often caused by clostridium difficile?
Pseudomembranous enterocolitis
In pseudomembranous enterocolitis, what is the pseudomembrane made of?
inflammatory cells, necrotic epithelium, and mucus in which the overgrowth of microorganisms takes place
Although colonoscopy and sigmoidoscopy are still employed, what is now the first-line diagnostic approach for pseudomembranous enterocolitis?
Stool testing for the presence of C. difficile toxins
What is a condition in which inflammation and injury of the large intestine occur as a result of inadequate blood supply?
Ischemic colitis
What region of the intestine is rarely affected by ischemic colitis and why?
The recturm because it received blood from both the inferior mesenteric artery and the internal iliac arter
What are the most common types of benign small bowel tumors?
Hyperplastic polyp Adenomas Stromal tumors - leiomyomas Lipomas Hamartomas
Describe the histological appearance of a leiomyoma.
Smooth muscle cells with elongated spindle cells containing cigar-shaped nuclei and no evidence of increased mitotic activity is seen.
What condition is an autosomal dominant disorder characterized by mucocutaneous pigmentation and benign GI hamartomas.
Peutz-Jeghers syndrome
Where do you find the lesions of Peutz-Jeghers syndrome?
Mucocutaneous pigmentation on the face, lips and buccal mucosa.
Benign hamartomas - small bowel (90%), stomach and large bowel.
What is the histological appearance of a lesion of P-J syndrome?
Frond-like appearance with a stromal/smooth muscle core that is covered by acinar glands and normal mucosa. Nuclear atypia is absent.
How common is primary cancer of the small intestine?
Relatively rare, accounting for only 2% of all GI cancers
What is the most common type of small bowel malignancy in the U.S.?
Adenocarcinoma
What is the most common type of cancer found in the small bowel? From where?
Metastatic disease
Melanoma, and colon, breast, ovary, pancreas and stomach cancers.
Carcinoid tumors arise from what? What do they usually secrete?
Neuroendocrine cells
Serotonin
What is the histological appearance of a carcinoid tumor?
Typical endocrine appearance with collections of small round cells containing nuclei that are consistent in size and shape and surrounded by cytoplasm which stains pink to pale blue.
What is a fleshy growth occurring on the lining of the colon or rectum? What is it a risk of developing into?
Colorectal polyp
Colorectal cancer
What is the most common type of polyp found in the colon?
Hyperplastic polyps
What can be described as rice grains on the colonic mucosa, with minimal epithelial atypia, where the cells display normal differentiation and maturation?
Hyperplastic polyps
What does a adenomatous polyp look like and what is it also known as?
Small, smooth, rounded.
AKA tubular adenoma because of the rounded nature of the neoplastic glands that form it.
What is the gross appearance of a villous adenoma?
Sessile, larger than a tubular adenoma.
The majority of the polyps found in this condition are non-neoplastic, hamartomatous, self-limiting and benign, but there is an increased risk of developing adenocarcinoma.
Juvenile polyposis syndrome
Histologically, a slide shows edematous stroma, eroded surface and cystic epithelial elements. What is the condition?
Juvenile polyposis syndrome
What condition is inherited and consists of hundreds to thousands of polyps formed mainly in the epithelium of the large intestine? What happens if it goes untreated?
Familial adenomatous polyposis
The polyps start out benign, but untreated there is malignant transformation into colon cancer
What is the combination of polyposis, osteomas, fibromas, and sebaceous cysts?
Gardner’s syndrome
What condition has a gross appearance of the mucosal surface of the colon being a carpet of small adenomatous polyps?
Familial adenomatous polyposis
What does adenocarcinoma look like microscopically?
Still glandular configuration, but the glands are irregular and are very crowded. Many of them have lumens containing bluish mucin. Hyperchromatism and pleomorphism are seen.
How is LeiomyoSARCOMA different from LeiomyoMA?
Both have increased cellularity, but leiomyosarcoma greater cell density and cells have more mitotically active nuclei.
What do non-Hodgkin’s lymphoma cells look like?
They have prominent clumped chromatin and nucleoli with occasional mitotic figures. They can be seen infiltrating through the mucosa.
While moderate hepatocyte swelling is reversible, more severe damage has irregularly clumped cytoplasmic organelles and large clear spaces. These may not be reversible. What is this process known as?
Ballooning degeneration
A dying (apoptotic) hepatocyte may shrink down to form what? What condition(s) is it associated with?
An eosinophilic councilman body
Viral hepatitis, yellow fever, other viral syndromes
What is iron overload in hepatocytes?
Hemochromatosis
What is copper overload in hepatocytes?
Wilson’s disease
What is triglyceride fat droplet accumulation in hepatocytes?
Steatosis
What is the most common cause of fatty change in developed nations?
Alcoholism
What category of liver disease involves quiescent lymphocytes collecting in the portal tracts which may migrate into specific areas of the periportal parenchyma as activated lymphocytes?
Viral hepatitis
What is a sign of very recent hepatocyte destruction?
Apoptotic hepatocytes
Apoptotic hepatocytes usually don’t incite a diffuse inflammatory reaction. However, scavenger macrophages (also known as what?) engulf the apoptotic cell fragments within a few hours, generating localized clumps of inflammatory cells which does what?
Kupffer cells and circulating monocytes
Activates a cascade of multiple cytokines
Unlike other responses which are reversible, what points toward a state of generally irreversible hepatic damage?
Fibrosis
Ongoing liver damage with liver cell necrosis followed by fibrosis and hepatocyte regeneration results in what?
Cirrhosis (nodular)
With cirrhosis, what do you see microscopically?
The regenerative nodules of hepatocytes are surrounded by fibrous connective tissue that bridges between portal tracts.
What type of disorders is by far the most frequent concerning the liver?
Inflammatory
Other than hepatitis A, B, C, D, and E, what viruses effect the liver?
Epstein-Barr
Cytomegalovirus
Yellow fever virus
How serious is HAV?
Benign, self-limited
Which hepatitis virus can involve (1) acute hepatitis with resolution (2) chronic hepatitis > mb cirrhosis (3) fulminant hepatitis w/massive liver necrosis and (4) the backdrop for HDV?
Hepatitis B
Which hepatitis virus is most widespread, globally?
Hepatitis B
What makes HBV so hardy?
- Prolonged incubation period
- Remains in the blood up to and during active episodes of acute and chronic hepatitis
- Present in all physiologic and pathologic body fluids except stool
- Withstands extremes of temp and humidity
What is the most common chronic blood-borne infection in the U.S. and accounts for almost half of all patients in the U.S. with chronic liver disease?
Hepatitis C
How is HBV transmitted?
Inoculations(IV drug use 60%) and blood transfusions. Risk of sexual transmission is low.
Which hepatitis virus is the highest risk perinatally?
HBV
What is generally the course of HCV?
Often undetected clinically. Once symptomatic it is indistinguishable from HAV/HBV, although it is often milder.
What is a characteristic clinical feature of chronic HCV infection?
Episodic elevations in serum aminotransferases.
What is the only way to prevent HDV and why?
Prevent HBV because the D virus is “replication defective” and requires genetic information from the B virus to replicate.
Where is HDV common?
Mediterranean, Middle East, Northern Africa. It is uncommon in the U.S.
Hepatitis E symptoms resolve over the course of 6 weeks. However, who should be worried about HEV?
Pregnant women; it can lead to fulminant hepatic necrosis and death (15-25%)
Which hepatitis virus is termed an “innocent bystander” virus?
Hepatitis G; no known pathogenic activity.
What is a liver parenchymal cell with a characteristic hazy staining appearance to the cytoplasm on light microscopy?
Ground glass hepatocyte
The classic ground glass appearance is associated with what condition and occurs as a result of what abundant substance?
Chronic hepatitis B; hepatitis B antigen in the endoplasmic reticulum.
What is the term used when hepatic insufficiency progresses from onset of symptoms to hepatic encephalopathy within 2 to 3 weeks?
Fulminant hepatitis
What may reactivate a latent HBV infection with fulminant hepatitis as a possible outcome?
HAV or non-heptotropic virus, drugs (acetominophen) or chemical toxicity.
Transection of a fulminant liver will reveal what?
Necrotic areas with a muddy, red appearance with blotchy bile staining.
What does Fulminant hepatitis look like microscopically?
Complete destruction of hepatocytes in contiguous lobules leaving only a collapsed reticulum framework and preserved portal tracts.
If a patient survives more than a week with a fulminant hepatitis, the liver can recover, potentially completely. Under what circumstances is the parenchymal framework preserved and what is this compared to?
With centrilobular zonal necrosis caused by direct hepatotoxins or by ischemia. With more massive destruction of confluent lobules, regeneration is disorderly.
What does alcohol impaired hepatic metabolism of methionine lead to?
Decreased intrahepatic glutathione (GSH) levels thus sensitizing the liver to oxidative injury.
Induction of what increases break down of alcohol in the endoplasmic reticulum and increases the conversion of acetaminophen to toxic metabolites (especially what)
Cytochrome P-450
NAPQI - N-acetyl-p-benzoquinone-imine
What is the antidote for acetaminophen poisoning?
N-acetyl-cysteine (NAC)
What is the leading cause of liver disease in most Western countries?
Excessive alcohol consumption
What three conditions are collectively referred to as alcoholic liver disease?
Hepatic steatosis
Alcoholic hepatitis
Cirrhosis
Describe the process of hepatic steatosis (fatty liver)?
The intake of alcohol causes microvesicular droplets of lipids to accumulate in hepatocytes. Chronic intake causes these globules to compress and displace the nucleus to the periphery.
What is the major intermediate metabolite of alcohol en route to acetate production that induces lipid peroxidation and subsequent oxidative damage?
Acetaldehyde
Hepatocytes may accumulate keratin and other proteins, which become visible as eosinophilic cytoplasmic inclusions. What is this called? What are they characteristic of?
Mallory bodies
Alcoholic liver disease
What is almost always accompanied by prominent activation of fibroblasts which give rise to fibrosis? What generally signals an irreversible stage of the disease process?
Chronic alcoholic hepatitis
The appearance of fibrotic bands
How many grams of daily ethanol intake is associate with significant risk? Severe injury?
80 gm
160 gm for 10 to 20 years
How does alcoholic hepatitis contrast to steatosis?
Acutely, usually following a bout of heavy drinking
What is a syndrome characterized by central nervous system dysfunction in association with liver failure including portal-systemic shunts?
Hepatic encephalopathy
What is one of the most common findings with portal hypertension? (what other organ is affected?)
Splenomegaly
What liver condition is strongly associated with obesity, dyslipidemia, hyperinsulinemia, insulin resistance and type 2 diabetes?
Nonalcoholic fatty liver disease (NAFLD)
What is presumed to be the most likely explanation for the elevated serum aminotransferases and/or GGT values documented in 24% of the the general U.S. adult population?
Nonalcoholic fatty liver disease (NAFLD)
What condition reveals the following on biopsy?: steatosis multifocal parenchymal inflam. Mallory hyaline bodies hepatocyte death sinusoidal fibrosis
Nonalcoholic steatohepatitis NASH
What are the usual primary and secondary causes of hemochromatosis?
Primary - genetic defect causing excessive iron absorption
Secondary - excessive administration of iron
What condition is an autosomal recessive disorder marked by the accumulation of toxic levels of copper in many tissues and organs, principally the liver, brain, and eyes?
Wilson’s disease
What sign in the eye is pathognomonic for Wilson’s disease?
Kayser-Fleischer’s ring
What is an autosomal recessive disorder marked by abnormally low serum levels of this protein that inhibits proteases which are normally released from neutrophils at sites of inflammation?
Alpha 1-antitrypsin deficiency
A1AT deficiency is more likely to cause disease where in the body in children vs. adults?
Liver in children
Lung in adults
Microscopically, periportal red hyaline globules with periodic acid-schiff (PAS) stain are characteristic of what condition?
A1AT deficiency
What condition is an autoimmune disease in which there are T cell mediated destruction of the bile ducts of the liver?
Primary biliary cirrhosis
What is the primary histologic feature of primary biliary cirrhosis?
Granulomatous destruction of medium sized intrahepatic bile ducts
What condition has hepatomegaly, xanthomas and xanthelasmas with later development of jaundice and severe pruritus?
Primary biliary cirrhosis
What is an important identifying lab for PBC? (95% sensitivity)
Positive anti-mitochondrial antibody test
What condition is associated with the bile ducts initially becoming inflamed, with segmental stricture and dilatation?
Primary sclerosing cholangitis
What do you expect to see with a barium swallow in a patient with primary sclerosing cholangitis?
Beaded appearance of intra-hepatic ducts
What condition do patients with primary sclerosing cholangitis also have 70% of the time?
Ulcerative colitis
What do the bile ducts look like histologically on biopsy for a patient with primary sclerosing cholangitis?
Onion skin pattern
What cancer is a primary sclerosing cholangitis patient at an increased risk for?
cholangiocarcinoma
