Liver Disease and Alcohol-Related Liver Disease - collins (INCOMPLETE _ DO X slides) Flashcards
when is hemoglobin broken down into
heme and globin
heme converted to biliviridin
what bilivurdin
converted heme that becomes unconjugated bilirubin (bound to albumin - fat soluble)
what are the four phases of bilirubin metabolism
production of bilirubin
uptake via liver cells
conjucation with glucuronic acid
transport via bile/urobilinogen
what is hyperbilirubinemia
impairment or dysfunction of any of the phases of bilirubin metabolism
what is the accumulation of bilirubin in the body clinically
jaundice
what is normal total bilirubin (indirect and direct)
0.2 - 1.2 mg/dL
what is normal newborn total bilirubin
1.0-12.0mg/dL
what are the lab values that jaundice is apparent around
2.5 - 3 mg/dL
what is unconjugated (indirect) hyperbilirubinemia
overproduction from hemolysis
impaired uptake secondary to certain drugs
impaired conjugation by glucoronyl transferse
what is overproduction from hemolysis
increased supply of unconjugated bilirubin overwhelms the liver
What is the clinical presentation of overproduction of hemolysis
sickle cell, hereditary spherocytosis, Rh incompatabiliy, transfusion reaction
normal stool color; urine color normal
increased indirect/unconjugated bilirubin
+ splenomegaly
what are impaired conjugation
physiological neonatal jaundice
gilbert syndrome
Crigler-najjar syndrome
what is impaired uptake
primarily a result of certain drugs
rifampin, chlecystographic contrast agents
? gilbert syndrome
what is the clinical presentation of impaired uptake
light to normal stool; normal to dark urine color
elevated indirect/unconjugated bilirubin
no bilirubin in urine
resolvves with removal of drug
what are the clinical presentations of impaired conjugation
light to normal stool; normal to dark urine
elevated indirect/unconjugated bilirubin
no bilirubin in urine
what is physiologica neonatal jaundice
fetal bilirubin cleared by mom
immature GT in newborns
develosp around days 2-5 of life in most newborns
what makes unconjugated bilirubin water soluble in physiological neonatal jaundice
UV light
what is Gilbert syndrome
hereditary disorder
reduced function of GT
episodic jaundice and hyperbilirubinemia
lifelong problem
What is Crigler-Najjar syndrome
autosomal recessive inherited GT disorder
partial to complete loss of GT - complete loss - type1, partial loss - type 2
primarily identified in neonates, persists throughout life
what is conjugated (direct) hyperbilirubinemia
decreased excretion of bilirubin
primarily a result of obstruction or hepatocellular dysfunction
-hard to differentiate on labs - elevated Alk Phos, elevated AST/ALT with hepatocellular problems
what are examples of hepatocellular dysfunction
hepatitis
cirrhosis
biliary cirrhosis
sepsis/infection
post-operative
cholangitis
sarcoidosis
lymphomas
toxns
what are obstructiosn
choledocholithiasis
biliary atresia
carcinoma of biliary duct
sclerosis cholantitis
pancreatitis
pancreastic neoplasma
What does liver function testing typically inclued
serum bilirubin
serum albumin
ALK phos
ALT/AST
INR (prothrombin time)
+/- urine bilirubin
+/- GGT (gamma-glutamyl tranferase)
+/- 5’-nucleotidase
what is the most common cause of AST/ALT elevation
NAFLD
when is AST > ALT
Alcohol-related liver injury and cirrhosis
what releases alkaline phosphate
gallbladder
what is low serum albumin typically reflective of
chronic liver disease/cirrhosis
what is elevated PT/INR reflective of
poor hepatocyte function
what are the vitamin K dependent clotting factors
10, 9, 7, 2
what is the definitive study for determining cause and severity of liver disorders
liver biopsy
when does acute liver failure occur
without pre-existing liver disease
what is fulminant ALF
development of hepatic encephalopathy within 8 weeks
what is subfulminant ALF
hepatic encephalopathy 8 weeks to 6 months after onset
what are the causes of Acute liver failure
acetaminophen (APAP) toxicity
idiosyncratic drug reactions
what is the presentation of acute liver failure
jaundice
bleeding disorders
encephalopathy / AMS
what are late complications of acute liver failure
systemic inflammatory response syndrome (SIRS) - from death of hepatocytes
Multisystem organ dysfunction
what are LFT findings with ALF
significant LFT dysfunction
APA - AST/ALT increase (>5000)
Serum amylase
elevated ammonia (NH3) level
elevated PT-INR
what is the treatment for ALF
admit to ICU for management of multiorgan failure
culture transplant team
what determines liver transport priority
MELD score (age >12)
what is progressive hepatocyte dysfunction and accumulation of fatty tissue
non-alcohol related liver disease - exists on a continuum
what is the continuum of liver disease
Normal liver - NAFLD - NASH - cirrhosis
What is NAFLD
common
hepatic accumulation of fat absent of significant ETOH consumption
M>W
Hispanic > caucaasian > black
what is NAFLD strongly correlated with
insulin resistance
what is NAFLD commonly associated with
Metabolic syndrome
Obesity (BMI >30)
T2DM
Dyslipidemia
what is the presentation of NAFLD
primarily asymptomatic
+/- RUQ discomfort
non-specific constitutional symptoms
+/- isolated hepatomegaly
how is NAFLD diagnosed
diagnosis of exclusion so must r/o ETOH liver disease
what is the treatment of NAFLD
no reliable treatments except lifestyle modifications
GRADUAL weight loss
anti-diabetic agents
tx of dyslipidemias
What is NASH
NAFLD + inflammation and fibrosis
2nd hit hypothesis: NAFLD + secondary insult
also reversible
what are risk factors for progression of NASH
obesity
older age
non-AA ethnicity
female
DM
HTN
higher AST, ALT, or AST: ALT
worse US
what is cirrhosis
end stage fibrosis and hepatocyte death
what causes cirrhosis
viral hepatitis (C&B)
Alcohol
NAFLD
drug toxicity
autoimmune metabolic liver disorder
what are the three stages of cirrhosis
compensated
compensated with varices
decompensated - ascites, variceal bleeding, encephalopathy, jaundice
what are the initial symptoms of cirhosis
fatigue
disturbed sleep
muscle cramps
weight loss
what are the later symptoms of cirrhosis
anorexia, N/v
reduced muscle strength, reduced exercise capacity
abdominal pain
menstrual irregularities (amenorrhea)
ED, loss of libido
sterility
gynecomastia
hematemesis
skin manifestations, vitamin deficiencies, weight loss, chronic wasting, jaundice, FIRM, PALPABLE, NODULAR LIVER
what is seen on labs with cirrhosis
macrocytic anemia
thrombocytopenia
prolonged PT-INR
AST and ALT elevations
Elevated bilirubin
low albumin
renal dysfunction
elevated BNP/ventricular dysfunction
low cortison
other hormone dysfunction
what imaging studies can be used to identify cirrhosis
US to asses liver size, for ascites, assess for hepatocellular carcinoma
doppler US to assess patency of hepatic, splenic and portal veins
CT/MRI with contrast to define any nodules
liver biopsy for cirrhotic histology
EGD for varices or UGI bleeding
what is the treatment of cirrhosis
abstain from ETOH, adequate caloric intake with increased proteins, sodium restriction for fluid retention, vitamin supplementations
HAV, HBV and pnumoccocal vaccines
yearly influenza
Liver transplant is curative
what is ascites
portal hypertension - third spacing
peritoneal fluid buildup
what is diagnostic and therapeutic for ascites
paracentesis - lights criteria
what are complications of paracentesis
bleeding
infection bowel performation
what is lights criteria
determines if something is transudative or exudative
looks at serum protein, serum LDH and pleural fluid LDH
what is the treatment of ascites
sodium restriction (<2,000mg/day)
spironolactone + furosemide
Large volume paracentesis (5L)
transjugular intrhepatic portosystemic hunt (TIPS)
what is spontaneous bacterial peritonitis
infection of peritoneal fluid
causes abdominal pain, icnreasing ascited, fever and progressive encephalopathy
how do you diagnose spontaneous bacterial peritonitis
culture of ascitic fluid with paracentesis
what is the treatment of spontaneous bacterial peritonitis
cefotaxime 2g
what is hepatorenal syndrome
characterized by Azotemia, macroscopic evidence of kidney injury, shock,
see oliguria, hyponatremia, low urinary sodium
what is the treatment of hepatorenal syndrome
dialysis (modified protocol) and TIPS
what is hepatic encephalopathy
altered CNS function from toxin buildup - ammonia
spectrum: day-night reversal - coma
what is hepatic encephalopathy precipitated by
constipation, opioids, hyovolemia, infection
what is the characteristic sign of hepatic encephalopathy
asterixis
what is the treatment of hepatic encephalopathy
lactulose or rifamixin to reduce ammonia (excreted in feces)
what is esophageal varices
dilated submucosal veins secondary to portal HTN
occurs in about 50% of pts with cirrhosis
high mortality rate with acute bleed
what are the signs and symptoms of acute UGI bleeding
hematemesis or “coffee ground” emesis
melena
what is the treatment of esophageal varices
fluid resuscitation and blood transfusion
FFP or platelet transfusions
adjunctive vitamin K
prophylactic abx: fluoroquinolones
octreotide for acute bleeding control
endoscopy
portal decompression
BBlockers
What is hepatocellular carcinoma (HCC)
85% of HCC associated with cirrhosis
hepatitis and ETOH cirrhosis at greatest risk for converstion
what are risk factors for hepatocellular carcinoma
male
age>55
asian or hispanic ethnicity
+FH
overweight/obese
tobacco use
DM
hypothyroid
what is the presentation of hepatocellular carcinoma
cachexia, weihgt loss, weakness
suden development of ascites
enlarging liver with palpable amss
what is the diagnostic test of choice for HCC
biopsy
what is the definitive treatment of cirrhosis and complications
TRANSPLANT
what are absolute contraindications of liver transplant
malignancy (except small HCC)
advanced cardiopulmonary disease (except heaptopulmonary syndrome)
sepsis
what is the MELD score
transplant patients prioritized
are HIV and Hepatitis contraindications for liver transplants
NO
What is the AUDIT - C
scoring for alcohol use disorder identification
what is the spectrum for Alcohol related liver disease
alcohol related steatosis - alcohol-related heapatitis -cirrhosis
what are risk factors for alcohol-related liver disease
genetics
gender (F>M)
concurrent APAP use
concurrent obestiy
concurrent DM
concurrent HCV
what is alcohol related liver steosis
reversible with ETOH dicontinuation
presensation similar to NAFLD
fatigue, anorexia, nausea and RUQ abdominal discomfort
what are the later lab findings with alchol related liver disease
AST: ALT > 2:1 (HIGH SUSPICION if >3:1)
AST rarely above 300, ALT often normal
elevated GGT helps differentiate from other causes of liver dz
elevated alk phos (<3xnml)
thrombocytopenia due to direct toxic effect of ETOH and hypersplenism
what imagine is used for diagnosis of Alcohol related liver disease
US to evaluate for steatosis
CT or MRI with contrast to rule out other causes
biopsy
what is the treatment for fatty liver
abstinence from ETOH
-mental health/detox/rehab, psychosocial interventions
-naltrexone
-disulfram (anatbuse)
- improve nutrition
-treat vitamin deficiencies
what is the treatment of cirrhosis
abstinence from ETOH
mental health, detox/rehab, psychosocial intervention
Naltrexone (avoid disulfram)
slows or halts progression
-improve nutrition, vitamin deficiencies, sodium restriction, regular exercise to prevent muscle wasting
what is the definitive treatment of cirrhosis
transplant
What is alcohol-related hepatitis
hepatocyte injury characterized by:
acute or chronic inflammation, fibrosis, parenchymal necrosis
what is the presentation of alcohol related hepatitis
recent period of heavy drinking followed by:
jaundice, fever, nausea, anorexia, generalized edema, RUQ abdominal pain, tender hepatosplenomegaly
what is seen on labs with alcohol related hepatitis
same as other alcohol related liver disease
AST:ALT >2:1 (HIGH SUSPICION IF >3:1)
elevated serum bilirubin
leukocytosis with left shift
elevated alk phos, GGT
what is the treatment of alcohol related hepatitis
abstinence from ETOH
??corticosteroids if severe
alternative: pentoxifylline (PDE inhibitor)
