Hepatobiliary System Flashcards
characteristics of hepatitis viruses
families
HAV-RNA picornavirus HBV-DNA hepadnavirus HCV-RNA flavivirus HDV-RNA delta virus HEV- RNA hepevirus
hepatitis viruses: trasmission
HAV-fecal oral (overcrowding and poor sanitation, containated water or food, raw or steam shellfish in US)
HBV-paraenteral, sexual, maternal fetal
HCV-primary blood
HDV- paraetenteral, sexual, maternal fetal
HEV-fecal-oral, esp with waterbone epidemics
“vowels hit your bowels” do not depend on envelope so not destroyed in gut
hepatits viruses: carrier
HAV-No HBV-Yes HCV-Yes HDV-Yes HEV-No
hepatitis viruses: incubation
HAV-short (weeks) HBV- long (months) HCV-long HDV-superinfection (HDV after HBV)-short; coinfection(HDV with HBV)-long HEV-short
hepatitis viruses: HCC risk
HAV-No HBV-Yes:intergrates into host genome HCV-Yes from chronic inflammation HDV-Yes HEV-No
hepatitis viruses: notes to remember
HAV-Asymptomatic (usually), Acute, Alone (no carriers)
HBV- non
HCV- chronic, cirrhosis, carcinoma, carrier
HDV-defective virus, dependent o HBV; superinfection leads to decreased prognosis
HEV- high mortality in pregnant women, enteric, expectant, epidemic
pt with no apparent liver disease who have mild unconjugated hyperbilirubinemia provoked by classical triggers? name disease and triggers?
Glibert Syndrome
-hemolysis, fasting, physical extertion, febrile, illness, fatigue, and stress
normal total bilirubin-0.1-1.0; direct 0-0.3
Liver enzymes that test
- functionality (4)
- intactness (1-example)
- biliary tract (2, which is non-specific and which is?)
- prothrombin time, bilirubin, albumin, cholesterol
- transaminases (ie. aspartate aminotransferases)
- alkaline phosphatase (non-specific) , and gamma-glutamyl transferase
a moderately elevated alkaline phosphatase of unclear etiology should be followed up with measurement of?
gamma-glutamyl
-alkaline phosphatase can be elevated in a number of tissues.
homobox genes encode for
DNA-binding transcriptoin factors
debranching enzyme deficiency vs glucose-6-Phosphatase deficiency vs glycogen phosphorylase (liver and muscle invovlement)
Cori disease incomplete glycogen degradation. alpha 1,16-glucosidic branch points cannot be degraded- “small dextrin-like material accumulates within cytosol of hepatocytes”, no fatty liver,
- G-6-phosphatase (aka Von Gierke’s disease) hepatic steatosis, no muscle involvement
- aka McArdle’s syndrome affects muscles, exercise intolerance, muscle pain, cramping, myoglobinuria, low blood lactate after exercise and excess glycogen in muscle biopsy.
deficiency in acid maltase-action and location of enzyme, name of disease, presentation: glucose levels, other organ involvement? histo findings?
lysosomal enzyme has both alpha 1,4 and alpha 1,6 glucosidase activity. Pompe’s disease, no hypoglycemia, instead cardiomegaly and severe hypotonia. histo shows abnormal glycogen accumulation within lysosomes
location of portal vein on CT- aorta, liver, IVC
- look for celiac trunk emerging off aorta at T12/L1 level
- just medal or within right lobe of liver
- anterior to IVC
location of poly-A tail in mRNA and relation to consensus sequence
3’ end, downstream of concsensus sequenence (AAUAAA)
hepatic processing of bilirubin (3 steps ):
1) carrier-mediated uptake of bilirubin
2) conjugation with glucuronic acid by UGT (uridine diphosphate-glucuronyltransferase)
3) biliary excretion of water-soluble nontoxic bilirubin glucuronides
unconjugated vs conjugated bilirubin
- bound to albumin, water insoluble, can’t be filtered by kidney
- non bound to albumin, water soluble, can be filtered and removed by kidney
name 4 diseases that can lead to hyperbilirubinemias
- Gilbert syndrome=problem with bilirubin uptake=unconjugated bilirubinemia (mild jaundice, little clinical consequences)
- Crigler-Najjar syndrome type I=problem with bilirubin conjugation (UDP-glucoronosyltransferase)=unconjugated bilirubin (jaundice, kernicterus, early death)
- Dubin-Johnson syndrome=problem with excretion of conjugated bilirubin=conjugated bilirubinemia (black liver, benign)
- Rotor syndrome=mild conjugated hyperbiliirubinemia (no black, liver)
effect of cirrhosis on estrogen levels? testosterone levels? effect of estrogen levels on body (3)? not musty body odor because?
estrogen levels increase because of livers inability to break them down,
also results from increase sex hormone binding globulin which binds free testosterone.
leads to gynecomastia, testicular atrophy, and spider angiomata
musty body odor is due to hyperammonemia
thiamine serves as a co factor for which three key enzymes?
- transketolase (ribulose-5 phosphate to fructose-6 phosphate in HMP shunt)
- alpha-ketoglutarate dehydrogenase (alpha ketoglutarate to succinyl CoA in TCA)
- pyruvate dehydrogenase (pyruvate to Acetyl-CoA in glycolysis)
how is copper absorbed? excreted?
- absorbed in stomach in duodenum copper is used to form ceruloplasmin*
- senesecent ceruloplasmin and unabsorbed copper are secreted into bile and excreted in stool which is primary route for copper elimination (90-95%)
- other route is through renal tubular secretion (5-15%)
which one is a transcription factor? Ras or C-Jun
- c-Jun along with c-Fos bind DNA
- Ras is a proto-oncogene that codes for a membrane bound G-protein that does not bind to DNA
role of prokaryotic 16S mRNA
- found in 30S subunit.
- rRNA that binds to Shine-Dalgarno sequence upstream of start codon on bacterial mRNA. needed for initiation of protein translation
which rxn does HMP shunt provide energy for? not ADP to ATP phosphorylation because?
- creates NADPH which is an electron donor for anabolic rxns (cholesterol and fatty acid synthesis)
- ATP is not formed or used in HMP shunt
explain mechanism of liver injury in pt positive of HBsAg? not viral cytotoxic effect and hepatocyte necrosis with following secondary inflammation b/c
- CD8+ lymphocytes response to viral antigens on cell surface results in hepatocyte damage
- hep B virus has not direct cytotoxic effect
aspiration of hydatid cyst (aka?) can cause? appearance? pt pop? not septic shock b/c?
- aka echinoccocus granulosus cysts
- anaphylatic shock
- calcified cyst “eggshell calcification”
- mediterranean, middle east, southern south america, iceland, australia* and new zealand
- overwhelming bacterial infection causes septic shock
main toxicity of isoniazid
- hepatotoxic (or hepatatitis- fever, anorexia, and nausea)
- peripheral nerve damage if B6 is not also administered
side effects of all protease inhbitors
- lipodystrophy (buffalo hump-increased fat on back and abdomen and less in extremeties)
- hyperglycemia (increased insulin resistance can lead to DM)
- inhibition of p-450
why not give rifampin with protease inhibitors (HIV pt with TB?) give what instead?
b/c rifampin is P-450 activator and will decrease serum levels of rifampin (inhibitor)
-give rifiabutin instead
liver cancer associated with vinyl chloride, arsenic, or Thorotrast
hepatic angioscarcoma
-aggressive and poor prognosis
mc malignant hepatic lesion
met from another primary site
CT contract of liver with multiple nodules and bright round structure on right
- liver with met cancer
- bright structure is stomach with contrast
pathogenesis of Wilson’s disease. presentation. treatment
- too much non-ceruloplasmin -bound serum copper
- causes injury to liver, CNS, lenticular nucleus, and cornea
- penicillamine (copper chelator)
TATA box is needed for
transcription initiation
presentation of acute hepaptisis. not prolonged puritis and fatigue b/c
- fever and dark urine (increased bilirubin)
- puritis is seen in scleorising cholangitis (diffuse inflammation and fibrosis of biliary tract)
hepatocyte injury vs hepatocyte death
- ballooning degeneration, diffuse swelling
- lobular architectural disruption and confluent hepatocyte necrosis “bridging necrosis”
- both cause mononuclear inflammation in sinusoids and portal tracts
inheritance patterns of classical galatosemia vs Lesch-Nyhan syndrome
- autosomal recessive
- X-linked recessive
give examples of viruses that replicate by
-one stranded DNA-template double stranded DNA-progeny one stranded DNA
parvovirus B19
give examples of viruses with this replication pattern
double strained DNA-template double stranded DNA-progeny double stranded DNA
papovavirus, adenovirus, hepesvirus, poxvirus
give examples of viruses with this replication pattern
-double stranded DNA-template (+)RNA-progency double stranded DNA
hepadnavirus (HBV) b/c of reverse transcriptase DNA polymerase that creates an intermediate (+) RNA strand
give examples of viruses with this replication pattern
-one stranded (+) RNA-template
(-) RNA- progeny one stranded (+) RNA
poliovirus
give example of viruses with this replication pattern
-one stranded (+) RNA-template double stranded DNA- progeny one stranded (+)RNA
reovirus (HIV)
give example of viruses with this replication pattern
-one stranded (-)RNA-template (+) RNA-progeny one stranded (-) RNA
influenza, measles, rabies
newborns of all mothers with hep b are given what a birth? what is given afterwards?
- passive immunity with hep B immune globulin (HBIG)
- active immunization with recombinant HBV vaccine (once baby’s immune systems is mature)
glycogen storage disorder due to deficiency of
- glucose-6 phosphatase
- glycogen phosphorylase
- debrancher enzyme
- alpha-glucosidase aka acid maltase
- hepatosplenomegaly (enzyme in liver only not muscle), lactic acidosis. (Von Gierke’s disease)
- poor exercise tolerance, no lactic acidosis (McArdle’s disease)
- hepatosplenomegaly, muscle weakness. Cori or Forbes disease
- hepatoslemomegaly, caridomegaly, hypotonia (Pompe’s disease)
sucrose becomes
lactose becomes
maltose becomes
- fructose+glucose
- galatose+glucose
- glucose+glucose
name phases of gastrin release? what mediates them? what reduces gastrin release
- cephalic, gastric,and intestinal
- vagal and cholinergic mech. present of gastrin (causes release of histamine from ECLs) in stomach. protein in stomach (minor role)
- intestinal influences (peptitide YY)-binds to enterochromaffin-like cells (cells with histamine) to block it’s relaase
parasitic destruction of myenteric plexi in esophagus, intestines, and ureters. presentaiton?
Chagas disease (Trypanosoma cruzi) -achalasia, megacolon, and megaureter respectively
what stain is used for appearance of Tropheryma whippelli? color? what does it is stain?
- PAS after washing with diastase (digest glycoprotein into malltose and glucose)
- magenta
- glycoprotein left in actinomycete membrane b/c it’s diastase resistant
what structure can become compressed in superior mesenteric artery syndrome? what causes this?
- transverse portion of duodenum
- caused by diminished mesenteric fat, pronounced lordosis, or surgical correction of scoliosis (lengthened spine results in decreased motility of SMA)
- all can lead to decreased angle between SMA and aorta
sucrlfate
binds to base of mucosal ulcers
protects against gastric acid
metoclopramide
doapmine antagonist with both central and peripheral effects
-treats GI motility disorders (gastroparesis) and prevents nausea and vomiting
misoprostol
PE1 analog used to treat NSAID induced peptic ulcers
presentation of achalasia on manometry? barium swallow?
decreased esophageal body peristalsis and poor relaxation of LES
-dilated esophagus with bird’s peak deformity of LES
circopharngeal muscle function. presentation if it’s dsyfunctional
contracts behind bolus in esophagus initiating peristalitic wave
-failure of muscle to relax results in choking of “food sticking” sensation and pain with swallowing
IgA protease is produced by? mech? mech of IgA.
- SHIN
- cleaves secretory IgA at hinge region making it ineffective
- binds and inhibits action of pili and fimbriae which normal mediate mucosal adherence and penetration
causes of secondary lactase deficiency
viral gasteroenteritis or other diseses that damage intestinal epithelium
-causes abdominal distention, flatuence, and diarrhea after lactose ingestion
lactose aka
galactosyl beta 1,4-glucose
what enzyme is deficient in lactose intolerance? what type of enzyme is it?
-lactase a type of beta glactosidase
metabolism of galactose to glucose and lactose
-galactose to galatctose-1 phosphate (glactokinase)
-glactose-1-phosphate+UDP glucose to UDP galactose + glucose-1-phophate (GALT-galactose-1-phosphate uridyl transferase)
-UDP galactose is epimerized to UDP-glucose (via UDP-glactose-4-epiimerase) and enter glycolysis pathway
or
-UDP galactose can be converted to gaactosyl beta 1-4 glucose aka lactose (lactose synthase)
small bowel mucosa of pts with lactase deficiency is?
-normal
- marked atrophy of intestinal villi
- distended macrophages in intestingal lamina propria
- collections of neutrohils within crypt lumina
- intestinal inflammation with scattered non-caseating granulomas
- massive infiltration of intestinal lamina propria with atypical lymphocytes
- celiac disease
- whipple disease
- ulcerative colitis
- Crohn disease
- gastrointestinal lymphomas
transmission of HBV vs HCV
- sexual + others (body fluids)
- not sexual +others
drugs metabolized by acetylation vs methylation
- INH
- axathioprine and 6-MP
how many t 1/2 lives does it take to excreted 50%, 75%, 87.5%, and 93.75% of a drug?
- 1 half live
- 2
- 3
- 4
middle aged obese femal with fever and prolonged episode of right upper quadrant pain after a fatty meal? not biliary colic b/c?
- acute cholecytitis
- usually briefer and without fever
male with long history of UC with fatigue and high ALP is
primary sclerosing cholangitis
homeless male with fever abdominal pain and jaundice
acute cholangitis
45 old -Caucasian female with long history of pruritus and fatigue with pale stool and xanthelasma? disease and histo findings?
primary biliary colic cirrhosis (PBC)
- anti mitochondrial antibodies
- extensive lymphocyte infiltration and granulomatous destruction of interlobular biile ducts
- hepatocellular swelling and necrosis Mallory bodies, neutrophil infiltration and fibrosis
- liver failure and centrilobular necrosis that can extend to entire lobule
- microvesicular steatosis
- swollen, reddish purple and tense capsule, severe centrilobular congestion and necrosis
- granulomatous bile duct destruction and lymphocyte-predominant portal tract infiltrate
- alcoholic hepatitis
- acetaminophen overdose
- Reye’s syndrome
- Budd-Chiari syndrome
- primary biliary colic
which test can definitively diagnose cystic duct obstruction (leading to acute cholecystitis)? why not non-obstructive biliary stones?
- HIDA scan (radionuclide is injected into liver and imaging is used to determine if galbladder is filled appropriately
- many asymptomatic pts have gallstones and this is not diagnostic of acute cholecystitis
virus with partially double-stranded circular DNA and reverse transcriptase
HBV
mech of H. pylori causing gastric vs duodenal ulcers?
- gastric-loss of mucosal layer
- duodenal-destruction of somatostatin producing mucosa increased pH (from unchecked gastrin production) which causes ulcers
pulsion vs true diverticula vs
traction
- only mucosa and submucosa layers, older pts due to increase intraluminal pressure
- all three layers, results from congenital abnormalilty
- due to inflammation and scarring, considered true, example is midesophageal diver from mediastinal lympadenitis
mc site of pulsion? complications
role of inflammation?
sigmoid colon b/c of strained bowel movements
painless rectal bleeding or diverticulitis are complications
mech of NAC treatment of acetaminophen toxicity?
N-acetyl cysteine provides sulfhydryl groups and also acts as a glutathione substitute and binds to toxic metabolite (NAPQI)
PE sign for adenocarcinoma of head of pancreas? risk factors? most important one*?
- Courvoisier sign (palpable but non-tender gallbladder)
- age (>50), smoking* (doubles one’s risk), DM, chronic pancreatitis, genetic predispostion (MEN, lynch, FAP)
NADH and glucose levels in liver cells for some who has
- alcohol overdose
- DM
- cocaine
- high NADH (b/c ethanol is being used as energy) and low glucose
- low glucose and low NADH
- increased glucose b/c of adrenergic activity
extrahepatic diseases of HCV
membranous glomerulopathy and mixed cryoglobinemia
steps of acute calulous cholecystitis that leads to necrosis
- gallbladder outflow obstruction causes distruption of protective layer
- bile salts (lecithin) irritate mucosa and cause inflammation
- gallbladder distends and occludes blood vessels causing ischemia
- bacteria invade
which mitochondrial enzymes require lipoic acid? and what disease is caused without them?
PDH (lactic acidosis)
alpha ketoglutarate DH and branched chained ketoacid DH (maple syrup urine disease)
mc outcome of HCV infection? not complete resolution b/c? risk of liver cirrohsis
mc outcome of HBV?
- stable chronic hepatitis
- only 15-45% recover completely
- less than half with chronic hep go on to develop cirrhosis (usually silent)
-acute hepatitis with mild or subclinical symp that eventually completely resolve
UC vs Crohns
- rectum is always involved, inflammation is limited to mucosa and submucosa only, continuous damage
- transmural inflammation, perianal fistulae, non-caseating granulomas
stages of alcoholic liver injury and labs to measure them?
- alcoholic steatosis (reversible) AST and ALT (just liver damage)
- alcoholic hepatitis (reversible) AST and ALT (just liver damage)
- alcoholic cirrhosis (irreversible) serum albumin and PT time (now liver synthetic function is gone)
useful marker for hepatocellular carcinoma? not CEA b/c?
- AFP
- serum marker for colon cancer
2 components of Reye’s syndrome
- hepatic dysfunction (vomiting but no jaundice)
- encephalopathy (cerebral edema)
HFE on short arm of chromosome 6
- hemochromatosis gene that encodes an HLA class I-like molecule
- affects iron absorption form GI tract
poor vs well differentiated SCC?
SCC in general look for nest of cells with abundant eosinphilic cytoplasm
- poor- no keratinization and very dark nuclei
- well differentiation-look for keratin (don’t confuse with goblet cells no papillae)
histo of barrett’s esophagus vs reflux esophagitis vs leiomyomas
-goblet cells!!
-elongation of papillae,
eosinophils no goblet cells
-spindle cells with fibrosis
mech of estrogen and progesterone induced gallstones
- estrogen induces cholesterol hypersecretion (activates hepatic HMG-CoA reductase)
- progesterone induced gallbladder hypomotility
glycoprotein that forms spheres and tubules 22nm in diameter
HBsAg
fluid filled space in organ is aka. bac that can cause this in liver?
abscess
staph via hematogenous seeding
-enteric bacteria by ascending the biliary tact or direct invasion from adjacent area
levels of cholesterol, phosphatidylcholine and bile salts associated with increased risk of gallstone formation?
- very high cholesterol (this is what nucleates to make cholesterol stone)
- lower levels of phosphatidylcholine and bile salt
name bacteria that can cause mutation in p53? name mutation and cancer it causes
- aspergillus species (grows on grains)
- makes aflatoxin that cause G:c to A:T tranversion in codon 249
- increases risk of hepatocellular carcinoma
two types of gastric adenocarcinoma
- intestinal-type look for cuboidal or columnar cells, well demarcated, can ulcer and look gastric peptic ulcers
- signet ring- look for signet ring, diffuse growth, “leather bottle stomach” lintis plastica
why can’t RBCs utilize ketones for energy?
missing the enzyme succinyl-CoA-acetoacetate CoA transferase (thiophorase)
location of promoters vs enhancers
enhancers can be anywhere
promotors are 25-70 bases upstream of associated genes
in acute hepatitis
cells that accumulate pigment vs cells that become acidophilic (aka-2 other names)
- Kupffer cell ingest cellular debris and can be filled with lipofuscin
- hepatocytes skrink, undergo nuclear fragmentation and become intenstly eosinophilic aka acidophillic bodies, Councilman bodies or apoptotic bodies
elevated transaminases is indicative of? name 2 major organs involved and symptoms. major PE finding
Wilson’s disease
liver-func abnormalities, portal HTN, hepatitis, cirrhosis
CNS-parkinsonian tremor, rigidity, ataxia, slurred speech, personality changes, depression or paranoia
-look for Kayser-Fleischer rings with slit lamp
total parenteral nutrition can cause gallstone formation how?
due to lack of biliary stasis from absent enteral stimulation or
- for those with ileal resections disturbance of enterohepatic bile acid circulations resulting in bile supersaturated with cholesterol
which virus obtains it’s envelope from nuclear membrane?
-herpesvirses
- glycogen-rich cuboidal epithelium
- columnar mucinous epithelium
- atypical cells forming papillary projections
- serous pancreatic neoplasms
- cystic neoplasms
- panceatic adenocarinoma
pseudocysts vs true cysts
- seen as a complication of acute pancreatitis-walls consists of granulation tissue and fibrosis
- true cysts have epithelial lining
signs of acute hepatitis? viral cause in young adults? histo exam shows
- anorexia, nausea, low grade fever, bilirubinuria (dark urine) and RUQ tenderness
- HAV
- hepatocyte balloning degeneration and apoptosis
causes of cholestatis
- intrahepatic
- extrahepatic
- drug induced (erythromycin and OCPs)
- primary biliary cirrhosis
- cholestatis of pregnancy
- primary sclerosing cholangitis
extrahepatic
- choledocholithiasis
- malingnancy (pancreatic or galbladder)
drugs more likely elminated by liver vs kideny
liver-more lipophilic (high Vd and good CNS penetration)
-low Vd (in blood)
presentation of hepatitis B vs C
B has a 30-180 day latent period and “serum sickness like” symps (malaise, fever, skin rash, pruritus, lymphadenoapthy and joint pain)
C’s presentation is mild and typically asymptomatic
what is relation to herpes virus to dermatitis herpetiformis?
their only relation is that their lesions look similar
- groups of small vesicles (papulovesicular rash)
- that’s it nothing else don’t let the USMLE fool you!!
papulovesicular rash on extensor surfaces is associated with what GI disease.
-celiac disease
portal vein thrombosis causes vs hepatic vein occlusion
- causes portal HTN, splenomegaly, and varicosities, no histological liver changes
- aka Budd Chiari syndrome look for centrilobular congestion and fibrosis
portal vein thrombosis vs other cause of portal HTN
no abdominal ascites b/c obstruction is presinusoidal
histo of HBV vs others
-ground glass appearing granular eosinophilic spheres (HBsAg)
Octreotide vs Ondasetron
- synthetic somatostain analog used to control symptoms of carcinoid syndrome
- antiemtic used in pts undergoing chemo, mech is to block 5-HT3 serotonin receptors
histo of carcinoid tumors. mc locations
- nest or sheets of uniform cells, eosinophilic cytoplasm and oval to round stipple nuclei (KEY HINT-look for cells with “minimal to no variation in shape and size”)
- ileum, appendix and rectum
mech of bleeding in Mallory-Weiss tears. not local inflammation b/c?
- increased intraluminal gastric pressure (vomiting, retching etc…)
- this causes chronic gastritis and esophagitis (wouldn’t see upper GI bleeding)
hepatic complication of alpha-1 anti-trypsin deficiency
- hepatitis with cholestatis esp in first 2 decades of life
- look for pts with prolonged neonatal jaundice
- on histo look for reddish pink periodic acid-Schiff positive granules of unsecreted A1AT in periprtal hepatocytes
is HAV anicteric or icteric?
- usually anicteric (no symptoms)
- can also present with an adverson to smoking
triad of skin hyperpigmentation, DM, and pigment cirrhosis with hepatomegaly
- “bronze diabetes”
- late hemochromatosis
mech of brown pigmented stones
- due to infections
- bac and injured hepatocytes release beta glucuronidase
- contributes to hydrolysis of bilirubin glucuronides and increases amt of unconjugated bilirubin in bile
lab findings for acute viral hepatitis alcoholic hepatitis hemocromatosis/wilson's disease primary biliary cirrhosis
- both ALT and AST are elevate with ALT>AST and rises in bilirubin
- AST:ALT ration greater than 2:1
- elevated ALT and AST b/c of cellular injury
- elevated ALP (bile duct destruction) and cholesterol
