Download Assessment 9 Hepatobiliary

PaPh Assessment 9 Professor Hints Answered
Gallstone and biliary disease: clinical features of cholecystitis and biliary colic, pathophys of development of
different types of stones
Clinical Features:
Acute Cholecystitis (“Sudden inflammation of gallbladder”): abdominal pain, fever
Biliary Colic (gallstones): abdominal pain, NO fever
Cholesterol Stones
Pigment Stones
Brown Stones
Cholesterol Supersaturation
Increased unconjugated
bilirubin in GB results in
increased precipitation of
bile salts with calcium
carbonate forming
“pigmented stones”
Usually results from
infectious condition
causing release of βglucoronidase (from
injured hepatocytes)
which causes removal
of glucoronyl groups
and increased
unconjugated bilirubin
in bile
Picture
Aging: ↓ 7-α-hydroxylase (less cholesterol into
bile)
Obesity: ↑ HMG-CoA Reductase activity (more
cholesterol synthesis, rate limiting step)
Estrogen: ↑ HDL (more cholesterol retrograde
transport from periphery)
Progesterone: ↓ ACAT (moves cholesterol away
from liver)
Etiology
Seen frequently in chronic
hemolysis (spherocytosis,
sickle cell, thallessemia’s)
Remember: Infectious
association
Main Idea: As we age we have decreased 7 alpha
hydroxylase therefore prone to cholesterol stones
Accelerated Nucleation
Note: Deoxycholine bile acid has a higher
propensity to form stones
Gallbladder Hypomotility
TPN decreases CCK and decreases motility of
gallbladder
Risk
Factors
Female gender, Age, Pregnancy, Oral
contraceptives, Total parental nutrition, Wt.
reduction (significant), ileal disease or bypass
surgery. “Female, forty, fertile”
Hemolysis conditions,
Asian heritage, PTN,
advancing age, cirrhosis
Infection (bacterial),
decreasing IgA
secretion, high activity
of β-glucoronidase
PaPh Assessment 9 Professor Hints Answered
Normal liver: functions of various cells, normal liver chemistries and what they mean
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Kupfer (Endothelial Cells): important part of immune response and phagocytosis of bacteria (only cell type
talked about specifically)
PT time & Albumin: Measure of synthetic capacity of liver (clotting factors (I,II,V,VII,IX,X) and albumin
made in liver)
o Urea,glucose,ketone bodies, plasma proteins, ceruloplasmin, transferrin, alpha-antitrypsin, alpha
fetoprotein, VLDL, etc. also produced but less useful clinically for general assessment of liver
function.
AST/ALT: Intracellular enzymes released into circulation upon injury
o AST also found in heart and skeletal muscle
o ALT is more specific for liver
ALP: derived primarily from bile canalicular cells (found in liver, gut, and bone), increased in bile duct
obstruction or injury
GGT: Most sensitive indicator of biliary tract disease, highest concentration in bile ductules, can be
induced by drugs. If ALP is elevated you use GGT to confirm it is from the liver (and not the bone or gut)
Bilirubin: Represents balance between input and hepatic removal
Ammonia: Elevated in chronic liver injury
Acute liver failure: causes and clinical features thereof, diagnostic tests necessary for workup, complications,
causes of mortality
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Causes: Viral (Hepatitis viruses A,B,D,E), CMV, EBV,Varicella, Adeno ** Viral is most common cause
o Drug and Toxin: Acetaminophen, halothane, NSAIDS, Herbals
o Ischemic: Shock, Budd-Chiari
o Metabolic: Wilson’s, Reye’s, Fatty liver of pregnancy
o Misc: Bacterial infection, malignant infiltration
Clinical Features:
o Usually less than 8 weeks from the onset of jaundice**
o Massive necrosis without preceding liver disease
o JaundiceEncephalopathyaltered mental statusFulminant hepatitis
o Liver size is usually large, but small upon collapse
o Vomiting is Common
o ↑ HR, BP, RR and fever are late signs
Diagnostic Tests:
o Serology for Viral etiologies
o Metabolic panels (ceruloplasmin, ANA, etc.)
o CBC,INR,AFP, albumin, etc.
o PT/INR are indicators of prognosis**
Complications:
o Encephalopathy
o Cerebral Edema is the most common cause of death in Acute Hepatic Failure **
o Hypoglycemia and lactic acidosis
o Respiratory Alkalosis
o Hypokalemia
PaPh Assessment 9 Professor Hints Answered
Inherited liver ds: clinical features of wilson’s ds, hemachromatosis, and α-1 antitrypsin def; how to dx and
how to tx
Disease
Clinical Features
Wilson’s
Hemochromatosis
α-1-antitrypsin def.
Excess copper
accumulation
Excess Iron Accumulation
Deficiency of this
protease results in
unopposed elastase
activity which can result
in destruction of alveolar
septa in lungs
panacinar emphysema
Deficiency in ATPase
which secretes copper in
bile
Skin pigmentation, Diabetes,
and Liver Cirrhosis, fatigue &
arthritis (2nd MCP joint),
restrictive cardiomyopathy,
hypogonadism
Predisposition to HCC
Kayser Fleischer rings,
basal ganglia atrophy,
Fanconi syndrome in
kidney’s (PCT disease)
Diagnosis
Can present as fulminant
hepatic failure
Increased serum copper
(Serum free copper
>25mcg/dl is typical of
Wilson’s)
Total copper is usually low
(due to low cerulopaslmin)
Mutation in HFE (C282Y)
protein which causes more
iron to be absorbed (intestinal
absorption)
The reason it is deficient
is that it is produced in
liver and is misfolded
stuck in ERcauses
liver cirrhosis via
mitochondrial autophagy
Genetic test for HFE
Phenotyping (PiZZ)
Increased Ferritin
Patients with liver disease
and emphysema should
raise suspicion
Increased Transferrin
Saturation (33% is normal,
>45% is iron overload)
Diagnosis is based on
genotype and biopsy
Decreased Ceruloplasmin
Treatment
Greater than 250mcg/gm in
liver is diagnostic of
Wilson’s (liver biopsy)
Penicillamine (has sx)
Trientrene and Zinc is the
treatment of choice
Diagnosis based on liver
biopsy and Gene Test
(C282Y)
Phlebotomy, avoid vitamin C,
Iron chelating agents
(desferoxamine)
Enzyme replacement,
smoking cessation, liver
transplant
Biopsy
Recall: Hepcidin is the protein that regulates iron absorbtion mostly ↑Hepcidin decreases iron absorption
PaPh Assessment 9 Professor Hints Answered
Alcohol and drug induced liver ds: dose necessary, clinical features, also of drug reactions
Alcohol:
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Native Americans are a high risk population.
>40-80gm/day for 5 years usually is sufficient for alcoholic liver disease
(12gm per alcoholic beverage on average)
AST>ALT normally in alcoholic liver disease
East Asians at more risk due to increased acetaldehyde
Ethanol + hemohromatosis = worse prognosis
Features: Macrovesicular steatosis, perivenular fibrosis, mega-mitchondria, Mallory bodies, and eventually
cirrhosis (micronodular cirrhosis)
Drug Induced:
As little as 2.5-4gm of Acetaminophen may be toxic in alcoholics, You can know the chart in the notes but if you
are in doubt give N-Acetylcysteine for Acetaminophen toxicity.
Clinical features: fatigue, jaundice, abnormal liver enzymes, hepatic failure
Relationships:
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Angioscarcoma and Vinyl Chloride
Oral contraceptives and hepatic adenoma,cholestasis, hepatic vein thrombosis, peliosis hepatis, focal
nodular dysplasia, and HCC
Amiodarne and “myelin” figures
PaPh Assessment 9 Professor Hints Answered
NASH: clinical features of steatosis and steatohepatitis, risk factors, pattern of liver fxn tests
Clinical features: Associated with metabolic syndrome (hyperglycemia, obesity, hyperlipidemia), limited
progression (10-15% develop cirrhosis). May have no symptoms or signs. On PE you may find: obesity,
hepatomegaly, spider angioma, palmar erythema’s.
Patterns of Liver fx. Tests: Unlike in alcohol AST is not >> than ALT. ALP may be elevated. Fatty liver can be
seen on CT or ultrasound. Predominately macrovesicular steatosis, can see ballooning and Mallory bodies. Some of
these cases develop into cirrhosis.
Etiology: More peripheral lipolysis which increases FFA’s, less hepatic lipolysis both of which cause accumulation
of fat in liver. Insulin resistance inhibits lipolysis in the liver. Two hits: 1) hepatic fat accumulation, 2) oxidative
damage via lipid peroxidation.
Risk Factors: Total Parenteral nutrition, Mexican American ethnicity, metabolic diseases such as
abetalipoproteinemia and hypobetalipopoteinemia, drug exposure, surgery
PaPh Assessment 9 Professor Hints Answered
Viral hepatitis: clinical features, distinguishing features of various types, including serology
Hepatitis Virus
A (RNA)
Clinical Features
Contaminated Food/Water (fecal oral), causes fulminant
hepatits (rarely)
Serology/Distinguishing Features
Anti HAV
*most resolve
B (DNA)
Acute: Hepatitis: Fever, Fatigue, Abdominal pain
STD, causes acute viral hepatitis, maternal to fetal
transmission is possible, also blood borne, can cause
chronic hepatitis (a lot less likely than HepC though)
HBsAg = ongoing infection
AntiHBsAg = resolution or
vaccination
*most resolve
Acute: Hepatitis: Fever, Fatigue, Abdominal pain
HBeAg, HBV DNA = active
replication and high risk of
transmission
Strong link to HCC (Can cause even without cirrhosis)
Anti-HBc: Definite exposure (not
from vaccination)
C (RNA)
Blood borne, causes chronic hepatitis (80%)
Acute: Hepatitis: Fever, Fatigue, Abdominal pain
Genotype 1: Hardest to treat (most prevalent in African
Americans)
Genotype 2: Easiest to treat
D (RNA)
E (RNA)
Tx. Ribavirin, Peg Interferon, Protease inhibitors
Needs HBV for infection
Fecal oral route, can be lethal in pregnancy
Anti HDV
Anti HEV
Chronic liver ds: pathophys of ascites and varices, features of spontaneous bacterial peritonitis
Varices due to high pressure in portal system leading to bleeds where the portal and caval systems anastomose.
Thrombocytopenia due to splenomegaly (recall splenic v. is part of portal flow) and decreased coagulation via liver
injury.
Ascites: due to increased resistance to portal venous flow resulting in increased flow to portal system which causes
an increase in lymph flow  leaks into the liver and intestines. Other contributions can be made
(hypoalbuminemia) increased renal sodium retention, etc.
Spontaneous bacterial peritonitis can be a complication from ascites which may not have increased WBC counts, no
tenderness, etc. May be clinically silent until sepsis occurs. (HE SAID THIS WAS ON THE TEST IN
LECTURE)
PaPh Assessment 9 Professor Hints Answered
Inflammatory bowel ds: distinguish among ischemic colitis, crohn’s and UC; clinical presentation, course of
ds, extra colonic manifestations; be familiar with other causes of colitis – general features
Clinical
Presentation
Course of Disease
Extra Colonic
Manifestations
Ischemic Colitis
Abrupt, collateral
circulation initially
followed by
vasoconstriction &
reperfusion injury,
severe abdominal pain
in excess of physical
findings “thumb
printing on XR”
Spontaneously
resolves most of the
time, occurs often in
elderly
Crohn’s
Skip lesions, usually
more in intestines and
proximal colon in
contrast to UC,
fistula’s common,
transmural
involvement, non
caseating granuloma’s
Ulcerative Colitis
Begins in rectum and
extends proximally,
diarrhea with mucous
and blood, no skip
lesions, often has
pseudopolyps, more
superficial than
Crohn’s, Crypt
Abscesses
Fistula’s, apthoid
ulceration, erythema
nodosum, Pyoderma
gangranosa,
Episcleritis, Uveitis,
Uric acid and olate
stones,
Hypercoaguable state,
neuropathy, gallstones
Primary Sclerosing
Cholangitis, SIRS in
fulminant colitis,
apthoid ulceration,
erythema nodosum,
Pyoderma gangranosa,
Episcleritis, Uveitis,
Hypercoaguable state,
neuropathy, gallstones
Other Causes of Collitis: Collagenous colitis, lymphoctic colitis, Behcet’s syndrome (oral,
genital apthae, ocular ds, skin ds, gi ds, neuro ds), Chronic Diverticulitis (perforations and
inflammation), Chronic Infectious Colitis (C. Difficle), Diversion Colitis (disruption of fecal
stream, ↓FFA)
PaPh Assessment 9 Professor Hints Answered