GI: Biliary and Hepatic Flashcards
cholelithiasis
-mc pt?
-name the type of stones– MC?
formation of gallstones from impaired metabolism of cholesterol, bilirubin and bile acids
Fat Female Forty Fertile Fair skinned
Three types: dep on chemical composition
- Cholesterol: yellow-grey
- formed from bile that is superst with cholesterol produced by liver
2a. Pigmented (brown)
- formed from calcium bilirubinate and FA soaps that bind to calcium
2b. Pigmented (black)
- Calcium + billirubinate with mucin glycoproteins
- assoc with chronic liver dz and hemolytic dz
- Mixed stones MC–both choleserol and pigmented
5 F’s?
Fair Fat Female Fertile Forty ****RF for cholelithiasis and then poss cholecystitis
Cholecystitis
inflammation of GB or cystic duct (duct that goes from GB to common hepatic duct.. together form the common bile duct)
Choledocholithiasis
Gallstones in the common bile duct
- now GB AND liver is getting back up of bile
- ->start to see LFTs go up and jaundice bc billirubin being spilled into blood stream
Cholangitis
biliary tract infection SECONDARY to obstruction of the common bile duct (choledocholithiasis)
*Fever, RUQ jaundice=Charcot triad
^traid + AMS + Hypotension
Obstruciton–infection–biliary stasis—bacterial overgrowth
LIFE THREATENING
Jaundice
- what is it caused by
- types
- characterized by?
caused by hyperbilirubinemia
TYPES
1. Obstructive–extrahepatic or intrahepatic obstructions
2. Hemolytic–prehaptic or excessive hemolysis of RBCs
characterized by
- dark urine
- yellow discoloration of scelra and skin
- light colored stools
whats the largest organ in the body
liver
what are the blood supplies to the liver
hepatic artery (oxygen) portal vein (nutrients)
majority of cells in liver are?
hepatocytes– they synthesize proteins, produce bile, regulate nutrients, conjugate bilirubin
causes of preheptatic jaundice
transfusion reactions
sickle cell anemia
autoimmune
causes of hepatic janduince
hepatitis CA cirrhosis congential drugs
causes of post hepatic jaundice
Gallstones inflammation scar tissue CA ***anything blocking the flow of bile into the intestine****
hepatobiliary mechanisms for jaundice— describe the steps
- intrahepatic obtructiev jaundice–>hepatocellular damange–>decr liver ability to excrete bilirubin–>conjugated and unconjugated hyperbilirubinemia–>biliruibin deposition in tissues aka jaundice
- extrahepatic obstructive jaundice–>bile duct obstruction (cholestasis)–>conjugated bilirubin accum. in liver and enters the bloodstream–>conjugated hyperbilirubinemia–>incr excretion of bili in urine + jaundice
- Heatolic mechanism–>hemolytic jaundice–>excessive lysis of RBCs–>hepatocytes cannot conjugate and excrete bili as rapidly as it forms–bili accumulates in BS–>UNconjugated hyperbilirubinemia
liver dz are generally categorized into?
- hepatocellular–>hepatitis, ETOH liver dz
- Cholestatic–>gallstones or malignant obstruction, primry biliary cholangitis
- mixed–drug induced liver dz
Liver function tests:
- ALT/AST?
- ALK-P
- aminotransferases–ALT and AST
- ALT is found in liver
- AST found in many other tissues (skel, heart, kidney, brain) - ALK-P: alkaline Phosphatase
- found in the liver bone gut and placenta
- elevated when there is obstruction to bile flow aka cholestasis
- **if GGT levels are also elevarted.. points to hepatic in origin
3.
what dz does not show increase in BOTH AST and ALT
ETOH liver dz
AST and ALT levels for ETOH liver dz
ALT-AST ratio may be 1:2 or more
**the higher the ratio more likely etoh is contriuting
albumin is decrease in whic dz states
chronic liver dz
nephrotic syndrome
malnutrition
inflammatory states–burns, sepsis, trauma
80% of bilirubin is deribed from?
the rest comes from?
RBC b/d
-rest comes from myoglobin b/d and liver enzymes
what is converted into bilirubin in the spleen
hemoglobin
where is hemoglobin converted into bilirubin?
spleen
define unconjugated bilirubin
waste product of hemoglobin breakdown into bilirubin in the spleen
- indirect bilirubin
- circulates in plasma, bound to albumin
- not water sol
- toxic– can cross BBB and cause neuro deficits
bilirubin/albumin complex NOT water solbule–so it cannnot be excreted in the urine—— it travels to the liver to be conjugated
define conjugated bilirubin
albumin/bilirubin complex dissociated once inside the liver:
-bilirubin then is conjugated (direct) into a water soluble form— excreted into the intestines–bacteria act on it to produce urobilinogen and urobilin–>excreted in urine
- loosely bound to albumin so it is water sol
- when present in excess– it is excreted in urine– why we see dark urine ONLY in conjugated bilirubin
- nontoxic
when does unconjugated hyperbilirubinemia develop
defect BEFORE the liver uptake of the unconjugated albumin/bilirubin complex
when does conjugated hyperbilirubinemia develop
defect AFTER hepatic uptake of the albumin/bilirubin complex
clinical jaundice becomes evident at what levels
> 2mg/dl
kernicterus
brain damage that can result from high levels of unconjugated bilirubin in a baby’s blood
dark urine results from?
CONJUGATED bilirubin build up
what drugs can cause jaundice
*is this unconjugated or conjugated
UNCONJUGATED: sulfonamides PCNs Rifampin Radiocontrast agent
causes of jaundice (conjugated hyperbilirubinemia)
decr intrahepatic excretion of bili:
- hepatocellualr dz: viral or ETOH hepatitis, cirrhosis
- primary biliary cirrhosis
- primary sclerosing cholangitis
Extrahepatic biliary obstruction:
- gallstones
- pancreatic (head) CA
- cholangiocarcinoma
causes of jaundice (unconjugated hyperbilirubinemia)
hemolytic anemias
red hepatic uptake of bili or impaired liver conjugation:
-drugs
-diffuse liver dz.. hepatitis or cirrhosis
neonatal jaundice
-physiologic vs pathologic—-causes?
Physiologic: COMMON in healthy newborn
-lack of liver matuirty to billirubin uptake and conjugation
assoc with hemolytic dz, metabolic and endo dz, liver abnormalities and infections
Pathologic: associated with severe illness
-RF: fetal-maternal blood type incompatability, premmie, exclusive BF, maternal age over 25, male gender, delayed meconium passage, G6PD, excess truama during birth
is neonatal jaundice MC unconjugated or conjugated
unconjugated
serious cases of neonatal jaundice can lead to?
kernicteurs– cerebral dysfunction and encephalopathy
when does physiologic jaundice present in newborn?
3-5 days of life
causes of unconjuagted hyperbili physiologic jaundice in newborn
- Breastfeeding jaundice
- Breast milk jaundice
- Prematuirty
BF jaundice
- presents?
- pathi
- tx
presents very early on–w/in 1st week after birth
PATHO: insufficient milk intake leads to dehydration resulting in hemoconcetration of bilirubin— baby is not eating enough– not enough BMs— bilirubin builds up
fewer BM=incr in enterohepatic circulation of bilirubin
VERY YELLOW
*must intervene
tx:
- phototherapy– it make bilirubin water soluble
- continue breastfeeding**
- supplemental PO or IV fluids (PO preferred)
Breast milk jaundice
- presents?
- patho ?
- tx
presents AFTER 1st week of life
PATHO:
*infant liver is not developed enough to process lipids, –can interfere with the breakdown of bilirubin
Baby is not as yellow as breastfeeding jaundice
*not as serious as breastfeeding jaundice and intervention not always necessary
TX:
*phototherapy
*
when does pathologic unconjugated causes of jaundice occur?
within first 24 hours of life
list the pathologic unconjugatd hyperbilirubinemia causes
unconj made in the SPLEEN!! so its related to hemolytic (destruction RBC) and non-hemolytic aka metabolism issues
Hemolytic–G6PD def, drugs, sepsis
Non-hemolytic: -sepsis -hypothyroidism -Gilbert syndrome -
if you see conjugated hyperbilirubinemia– what is the immediate next step to take and why?
get abdominal US to rule out biliary atresia bc this is life threatening
Gilbert Syndrome
- define
- -defect?
- cm
genetic disorder of bilirubin metabolism
-defect is reduced activity of the enzyme UDP that b/d bili
-high levels of unconjugated bili
CM: very mild jaundice during times of physiologic stress…. illness, dehydration, etc)
Viral hepatitis:
- list the types–MC?
- can cause?
- phases
5 types: A B C D E
B AND C MC**
Can cause: acute, icteric illness
Phases:
- incubation:
- prodromal
- icteric
- recovery
Hep B and C cirrhosis are imp RF for?
Hepatocellular carcinoma
Hep A Virus
- type of virual genome
- transmission
- incubation pd
- diagnosis (acute vs past exposure)
- possible chronic infection?
- vaccine?
- type of virual genome–RNA
- transmission–fecal oral
- incubation pd–14-28 days
- diagnosis
1. IgM Anti-HAV-specific antibodies–acute
2. IgG HAV antibody with negative IgM - possible chronic infection?–no
- vaccine?–yes
Hep B Virus
- type of virual genome
- transmission
- incubation pd
- diagnosis (acute vs past exposure vs resolved)
- possible chronic infection?
- vaccine?
- type of virual genome–DNA
- transmission–blood and other body fluids
- incubation pd–30-180 days
- diagnosis (acute vs past exposure)
1. ACUTE INF: +surface HBV antigen protein, positive core IgM antibody
2. Chronic: +surface antigen, positive core IgG AB
3. resolved infection: + surface antibody, positive core IgG antibody - possible chronic infection?–YES
- vaccine?–yes
Hep C:
- type of virual genome
- transmission
- incubation pd
- diagnosis (acute vs chronic)
- possible chronic infection?
- vaccine?
- type of virual genome–RNA
- transmission–blood
- incubation pd–14days -6MO
- diagnosis (acute vs past exposure)
1. HCV RNA (more sensitive)
2. Anti-HCV-AB
3. chronic: both HCV RNA and Anti-HCV positive - possible chronic infection?–yes
- vaccine?–no
Hep D:
- type of virual genome
- transmission
- incubation pd
- diagnosis (acute vs past exposure)
- possible chronic infection?
- vaccine?
D for “defective” virus
*requires Hep B to cause co or superimposed infection
- type of virual genome–RNA
- transmission–Blood and other body fluids
- incubation pd–requires Hep B for replication
- diagnosis (acute vs past exposure)
1. Anti-HDV Antibody
2. HDV RNA
3. also do HBV serologies - possible chronic infection?–yes
- vaccine?–no
Hep E:
- type of virual genome
- transmission
- incubation pd
- diagnosis (acute vs past exposure)
- possible chronic infection?
- vaccine?
- type of virual genome–RNA
- transmission–fecal-oral
- incubation pd–14-70 days
- diagnosis (acute vs past exposure)
1. Anti-HEV AB
2. HEV RNA - possible chronic infection?–Yes
- vaccine?–No in US…. but yes in china
how does a baby MC get Hep B?
infected by their mothers
% of Hep A infections occur in kids?
30-50%
which hepatitis can cause chronic infection in kids? MC?
HCV and HBV MC
Fatty Liver Dz
- also called?
- list the two types
Steatohepatits
- Alcoholic liver Dz
- Nonalcoholic Fatty liver Dz (NAFLD)
ETOH effect on liver
direct toxin to the hepatocytes
*messes with FA oxidation– causing fatty liver + oxidative stress–kills hepatocytes–inflammation and fibrosis of liver
when cells die– leaks out their content which causes inflammation
Non alcoholic fatty liver dz
- patho
- etiologies
- can progress to?
infiltration of hepatocytes with fat
occuring in the absence of ETOH intake
*fat accumulation– creates inflammation– incrs oxidative stress
Can progress to– NASH: non alcoholic steatohepatitis–>can progress to cirrhosis–>end stage liver dz
**very common
etiologies:
- obesity
- hyperlipidemia
- glucocorticoid use
- DM
difference b/w NASH and NAFLD
NAFLD–relatively benign, not associated with fibrosis or malignant potential
NASH–assoc with inflammation and fibrosis, potential to progress to cirrhosis— can be premalignant
whats a very common reson for incr LFTs?
nonalcoholic fatty liver dz
Acute liver failure aka?
Fulminent hepatits
timing for acute hepatitis
> 6 MO
MCC of fulminant hepatitis (adults and kids)
Adults–acetominophen OD
kids– MCC is idiopathic, second MC is tylenol
reye syndrome
kids are given ASA during or after a viral infection– can lead to fulminant hepatits
cirrhosis
- define
- reversible?
- two major physiologic events + their subsequent issues
- how do we assess functional reserve?
- chronic liver dz
- fibrosis, disruption of liver architecture & widespread nodules in lover
- fibrous tissue replaces damaged or dead hepatocytes
- typically irreversible
**inflammation starts the process— very important to note
inflammation–>hepatocyte death–>scarring/fibrosis–>cirrhosis + portal HTN
- **the distortion of liver anatomy causes:
1. Decreased blood flow thru liver—biliary channels become blocked–> HTN in portal circulation—>ascites, periph edema, splenomegaly, varicosity of veins
- Hepatocellular failure–>impariment of biochemical functions such as: decr albumin synthesis and decr clotting factor synthesis
Assess hepatic functional reserve:
- Child-Pugh Score*estimates the hepatic reserve in liver failure–measures dz severity and predictor of morbidity and mortality
- Class C= more severe
- Class A=milder
what do we need to worry about with a cirrhotic patient going NPO
hypoglycemia**
because there is impaired gluconeogenesis
complications from cirrhosis
- portal HTN–abnormally high pressure in the portal venous system caused by resistance to portal blood flow
- ->intraheptic or posthepatic
Portal HTN can then further cause:
1. varices
- splenomegaly–>hepatopulmonary syndrome and portopulmonary syndrome
- Vomiting blood from bleeding esoph varices
Portal HTN
- develops when?
- worsened by?
- where is resistance
- CM?
- MCC in developed world ?
- dev when resistance to portal blood flow
- worsened by increased portal collateral blood flow
- resistance MC in liver (cirrhosis)
- can be prehepatic: portal vein thrombosis
- can be posthepatic: Budd-Chiari syndrome
Often asymptto UNTIL complications develop—–splenomegaly, abdominal wall collateral vessels, thrombocytopenia (cannot clot properly)
MCC is cirrhosis–dev world
MCC is schistosomiasis (parasite) in underdev world
how does liver dz lead to bleeding varices?
- cirrhosis of liver: causes incr in intrahepatic vascular resistance due to architectural distortion and deficiency of NO
- Portal HTN–>results from incr intrahepatic resistance (decr outflow) + splanchnic arteriolar vasodilation (increased inflow)
- Varcies form in esophagus and stomach by dilation of preexisting vessels and by active angiogenesis–>they increase in size w/ severity of portal HTN–can rupture and bleed when pressure reach maximal point
varices develop seconary to?
- result of?
- % of cirrhotic PTs with varices
portal HTN
result of: collateral circulation
50% of cirrhosis pT have varices
Ascites
- define
- MCC
- development of it?
- mortality rate? %
accumulation of fluid in the peritoneal cavity
MCC=cirrhosis
Development:
1. portal HTN–>decreased synthesis of albumin by liver–>decrs oncotic pressure–>splanchnic vasodilation–>renal sodium and water retention–>activates RAAS system
25% mortality rate in 1 yr if associated w/ cirrhosis
**decrease in the oncotic pressure moves fluid from the vascular space into the tissue
hepatorenal syndrome
- define
- types
- lab work to show this?
functional renal failure that develops as a complication of adv liver dz
Type 1: rapid: trigger–>sepsis or ETOH binge with a bad liver –HIGH mortality rate– weeks
Type 2: slow: diruetic resistance–still bad prognosis but takes months
CM:
Oliguria–small amt of urine
complications of adv liver dz
Lab work: rise in Creatinine in a cirrhotic patient—VERY SERIOUS*****
Hepatic Encephalopathy
- patho?
- dev quickly with?
- dev slowly with?
- early s/s
- later s/s
- tx?
live failure–>inc ammonia levels–>increas in b/d of ammonia into glutamine in the brain–>acts like a neurotoxin
quickly with fulminant hepatitis
slowly with liver dz
early: subtle changes in personality, memory loss, irritability, disinhibition, lethargy and sleep disturbance
later: confusion, disorientation to time and space, flapping tremor (asterixis), slow speech, bardykinesia, stupor, convulsions, coma
TX:
-lactulose helps via inhibition of ammonia production in intenstines
gluatmine has what kind of effects on braiN?
excitatory– can cause cerebral edema
Wilson Dz
-what is it
autosomal recessive defect of COPPER metabolism
*causes toxic levels of copper to accum in liver, brain, kidneys, cornea
- copper cannot metabolized
- mutation of the ATP7B gene–>impairment Cu excretion into the bile–> (normally in the bile Cu is converted into ceruloplasmin and excreted out) but this does not happen and Cu accumulated to toxic levels
Liver Cancer
- etiology
- types + CM
MC caused by mets spread from a primary site elsewhere
- hepatocellular carcinoma: associated with HBV/HCV and cirrhosis—- usuually asympto
- Cholangiocellular carcinoma (CA of biliary tree)–CM is insidious… pain, loss of apeptie, wt loss, gradual onset of jaundice
Gallbladder CA
-causes?
usually caused by mets
- chronic inflammation may trigger dysplasia and progress to met
- early stages usally asympto
- MC caught in later stages
