Clinical Medicine of the Hepatobiliary System

Dentist have the most increased exposure risk to which hepatitis viruses?

-Hep B

-Hep C

True or False: Alcoholism is more prevalent amongst dentists than in the general population

False ==> rate of alcohol & drug use disorders in dentists is the same as the general population

True or False: Liver disease can have oral manifestations

True

Why is it important to evaluate coagulation factor levels in patients?

need to evaluate bleeding risk in patients

*pts w/ liver dysfunction are at high risk of bleeding

Name the tests that are used to evaluate liver function.

-total protein

-albumin

-total bilirubin --> unconjugated (indirect); conjugated (direct)

-alkaline phosphatase (AlkP)

-Aspartate aminotransferase (AST)

-Alanine aminotransferase (ALT)

-y-glutamyl transpeptidase (GGT)

-prothrombin time/INR --> measure of coagulation

-ammonia

Can you make a diagnosis based solely abnormal liver function tests?

no ==> lab tests aren't specific to liver (can be abnormal with other systems)

*diagnosis in combo w/ patient history & physical + patterns of lab abnormalities

What is the breakdown product of hemoglobin?

bilirubin

what is unconjugated bilirubin?

bilirubin that is bound to albumin in blood as it travels to the liver

How is bilirubin processed in the liver?

conjugated & excreted

jaundice

yellow discoloration of the skin, sclera, & mucosa due to elevated blood levels & deposition of bilirubin

What is an associated symptom of jaundice?

pruritis (itchiness)

How is jaundice subdivided?

-pre-hepatic jaundice --> due to hemolysis

-hepatic jaundice --> due to liver disease

-post-hepatic jaundice --> due to biliary obstruction

pre-hepatic jaundice

jaundice due to increased hemolysis

hepatic jaundice

jaundice due to liver disease

post-hepatic jaundice

jaundice due to biliary obstruction

What percent of bilirubin in blood is unconjugated?

70%

What causes elevated unconjugated bilirubin?

-intravascular hemolysis --> RBC breakdown (pre-hepatic)

-Gilbert Syndrome --> impaired conjugation, genetic, benign, jaundice (hepatic)

Would you expect unconjugated or conjugated bilirubin levels to be elevated due to intravascular hemolysis?

unconjugated ==> pre-hepatic jaundice

Would you expect unconjugated or conjugated bilirubin levels to be elevated in Gilbert Syndrome?

unconjugated ==> hepatic jaundice

gilbert syndrome

hepatic jaundice due to impaired conjugation, genetic, benign, jaundice can be brought on by stress

Which conditions cause elevated conjugated bilirubin?

-hepatocellular disease--> cirrhosis, hepatitis, drugs (hepatic jaundice)

-cholestasis (hepatic)

-obstruction --> gallstones, cancer (post-hepatic)

Would you expect elevated unconjugated or conjugated bilirubin in patients with a hepatocellular disease?

conjugated ==> hepatic jaundice

ex: cirrhosis, hepatitis, drugs

Would you expect to see elevated unconjugated or conjugated bilirubin in patients with cholestasis?

conjugated ==> hepatic jaundice

Would you expect elevated unconjugated or conjugated bilirubin in patients with obstructions due to gallstones or cancer?

conjugated ==> post hepatic jaundice

What are the 2 sensitive indicators of hepatocyte injury?

-AST --> less specific b/c also present in cardiac & skeletal muscle, & kidney

-ALT

*these enzymes usually stay in hepatocyte--> increase in blood indicates hepatocyte injury

Of the 2 sensitive indicators of hepatocyte injury, which one more specific to the liver?

ALT

What does a spill of AST and ALT into the bloodstream indicate?

acute hepatocellular injury

True or False: Elevated AST and ALT indicates hepatocyte cell death.

False ==> elevated levels indicates injury not necessarily cell death

True or False: Elevated AST and ALT does not correlate with the degree of injury

True

Which conditions cause very high AST & ALT levels (> 1000)?

-drugs/toxic insult --> tylenol toxicity

-acute hepatitis infection

-ischemia/shock

Which conditions cause moderately elevated AST and ALT (250-1000)?

-viral infections such as EBV, HSV

-drugs (NSAIDs)

-autoimmune hepatitis

-wilson's disease

Which conditions cause mildly elevated AST and ALT (<250)?

-fatty liver disease

-drugs

-cholestasis

-infection

-alcohol --> 2:3 AST:ALT ratio

-non-liver disorders --> celiac, muscle disease, intense exercise

Toxic insult to the liver has what effect on AST & ALT levels?

very high AST & ALT (>1000)

Acute hepatitis infection has what effect on AST & ALT levels?

very high AST & ALT (>1000)

Ischemia and shock has what effect on AST & ALT levels?

very high AST & ALT (>1000)

Viral infections such as EBV and HSV has what effect on AST & ALT levels?

moderate elevated AST & ALT (250-1000)

NSAIDs have what effect on AST & ALT levels?

moderate elevated AST & ALT (250-1000)

Autoimmune hepatitis has what effect on AST & ALT levels?

moderate elevated AST & ALT (250-1000)

Wilson's disease has what effect on AST & ALT levels?

moderate elevated AST & ALT (250-1000)

Fatty liver disease has what effect on AST & ALT levels?

mild elevation (<250)

Cholestasis has what effect on AST & ALT levels?

mild elevation (<250)

Infection has what effect on AST & ALT levels?

mild elevation (<250)

Alcohol has what effect on AST & ALT levels?

mild elevation (<250)

* 2 AST : 3 ALT

True or False: Celiac disease causes mild elevation of AST & ALT levels

True

True or False: Muscle disease causes mild elevation of AST & ALT levels

True

True or False: Intense exercise causes mild elevation of AST & ALT levels

True

What could elevation of alkaline phosphatase (AlkP) indicate?

biliary system

alkaline phosphatase (AlkP)

enzyme found in liver, biliary system, bone, placenta, kidney, placenta, intestines

Which hepatic conditions present with elevated AlkP?

-bile duct lesions

-primary biliary cirrhosis

-primary sclerosing cholangitis

-drug induced cholestasis--> anabolic steroid

-liver cancer

True or False: AlkP can be normally elevated in 3rd trimester of pregnancy

False

True or False: AlkP can be normally elevated in adolescence.

True ==> due to high bone growth

True or False: Patients who have diseases with high bone turnover have elevated AlkP

True

True or False: Metastasis to bone have elevated AlkP

True

True or False: TB causes elevated AlkP

True

Where is albumin synthesized?

liver

What is the half-life of albumin?

20 days

what do you expect the albumin levels to be in acute liver disease?

normal (even if low synthesis)

What do you expect the albumin levels to be in chronic liver disease

low

What is a major consequence of low albumin levels in the blood?

decreased oncotic pressure --> lead to ascites and/or edema

What can cause decreased albumin levels?

-liver disease

-malnutrition

-protein losing enteropathy

-nephrotic disease (kidneys)

-chronic infection

Why is INR used over prothrombin time to analyze coagulation?

b/c PT measurements vary in labs

Which clotting factors are synthesized in the liver?

-II

-V

-VII

-X

*the vitamin K dependent factors

Elevated INR = ?

longer clotting time

What effect does factor deficiencies and/or liver disease have on PT and INR?

-prolong PT

-elevated INR

Would you expect INR to be elevated or decreased in patients taking warfarin?

elevated

What is the most commonly overdosed medication?

acetaminophen

What is the maximum daily dose of tylenol in healthy patients?

4 grams (8 extra-strength tabs)

What is the maximum daily dose of tylenol in patients with liver disease or regular alcohol use?

2 grams (4 extra-strength tabs)

What are the symptoms of acetaminophen overdose?

-1st 30 min --> asymptomatic or vomiting

-18-72 hrs --> vomiting, Right upper quad pain

-73-96 hrs --> jaundice, significant liver dysfunction, renal failure, coagulopathies, acidosis, encephalopathy, death

What is the antidote for acetaminophen overdose?

N-acetylcysteine

What is the treatment for acetaminophen overdose?

-antidote = N-acetylcysteine

-supportive care at liver transplant site if evidence of failure

-most common reason for emergency liver transplantation in US

Why do GI doctors still recommend acetaminophen over NSAIDs for patients with liver disease?

-less risk of GI bleed

-safer in patients with coagulopathy

-less interaction with medications

-less toxic to kidneys --> liver failure can lead to kidney failure

Hepatocellular necrosis is found in which zone of the liver acinus in acetaminophen toxicity?

zone 3

Describe the lab work of patients with fulminant liver failure due to acetaminophen overdose

-multiple lab abnormalities

-multiple organ findings

What is the 7th leading cause of death worldwide?

viral hepatitis

what are the symptoms of acute hepatitis?

-nausea

-abdominal pain

-fatigue

-malaise

-jaundice

*symptoms of range in severity

which types of hepatitis are usually symptomatic?

-Hep A

-Hep B

True or False: Hep C is always symptomatic

False ==> can be asymptomatic (subclinical)

True or False: Acute hepatitis can resolve over days to months

True

Which hepatitis viruses can cause chronic infections?

-Hep B

-Hep C

*higher risk for cirrhosis & hepatocellular carcinoma

What are the risks of HBV & HBC?

can become chronic hepatitis & :

-increase risk for cirrhosis & hepatocellular carcinoma

-remain asymptomatic carriers & transmit the disease

What other viruses can cause hepatitis?

-cytomegalovirus

-epstein-barr

-herpes simplex

Describe the labs of patients with acute hepatitis.

-very high AST & ALT (>1000)

-elevated bilirubin

What will you start to see in labs if acute hepatitis progresses to acute liver failure?

elevated PT & INR

What is characteristic of fulminant liver failure die to acute hepatitis A or B?

hepatic encephalopathy ==> can be fatal

What is the incubation period of Hep A?

15-45 days

What is the route of infection of Hep A?

-contaminated water or food (shellfish)

-can spread quickly in families & institutions

-can be sexually transmitted

True or False: Hep A has high transmission in healthcare workers

False==> has low transmission

What are the symptoms of Acute Hep A?

-nausea

-ab pain

-fatigue

-malaise

-jaundice

-may have cholestatic hepatic failure

-may have relapsing course over a year

True or False: Hep A does not lead to chronic hepatitis

True ==> doesn't have carrier state

Describe the treatment of Hep A

supportive

Is a vaccine for Hep A available?

yes ==> for at risk populations --> travel, drug users, occupational risks, cirrhosis

Labs in Acute Hepatitis A

-very high AST & ALT (>1000)

-elevated bilirubin

-elevated Alkaline Phosphatase

Describe the Serology of Hep A Infection

-IgM & HAV --> acute state

-IgG anti-HAV --> immune state (lifelong)

How is Hep B transmitted?

-sexual contact

-IV drug use

-blood

-vertical transmission

Which dental professional is at the greatest risk of Hep B infection?

oral surgeons

Which healthcare worker is at the greatest risk for Hep B infections?

dentists (3-4x)

How do dentists typically contract Hep B?

-puncture wounds with infected instruments

-absorption thru mucosa (oral or eyes)

What is the incubation period for Hep B?

30 - 180 days

Does viral shedding of Hep B start before or after symptoms of infection?

starts before symptoms