TRUE or FALSE. Plasma activators of fibrinolysis are cleared by the liver
Describe the importance of the liver to RBCs
RBCs release Hgb, then heme forms bilirubin which is conjugated by the liver
What does the liver store that is important for things like Hgb and myoglobin?
Liver stores excess iron needed for Hgb, myoglobin, cytochrome
Describe the livers role in CHO metabolism
Glucose stored as glycogen
Glycogenolysis (breaking down of glycogen into glucose)
How much glycogen is stored in the liver?
100 g glycogen stored in liver (400 g in skeletal muscle)
When is Gluconeogenesis an important liver function?
Important source of glucose after glycogen stores depleted (after 12 - 24 hours of starvation) need to create glucose from non-CHO sources
Describe the liver's role in fat metabolism
Excess CHO & protein converted to fat
Formation of lipoproteins (needed for fatty acid transport)
Oxidation of fatty acids to acetoacetic acid (comes from Aceytl-Co-A which is the common intermediary of the Krebs cycle for ATP production)
Describe the livers role in protein metabolism
How many grams of Albumin does the liver synthesize per day?
10 – 15 grams/day
What % of capillary oncotic pressure is albumin?
80-90% of capillary oncotic pressure
One of the livers functions is the removal of hormones. List some hormones that are removed by the liver
An important function of the liver is the detoxification of drugs. Describe how the liver does this.
Phase 1 and phase 2 reactions involved in drug detoxification.
Phase 1: oxidation reduction reactions
Phase 2: conjugation reactions.
All managed by the cytochrome P450 system
Whole purpose of those reactions is to create a polar water soluble substance that can’t be reabsorbed by the kidney.
Liver also produces enzymes needed for ester hydrolysis. Drugs like: Succinylcholine and Remifentanil.
What is the % Hep A, B, C, & D incidence in the US?
HAV – 50%
HBV – 35%
HCV – 15%
HDV – less than 1%
Which types of hepatitis virus may result in chronic infections?
Chronic infections may result from B, C, and D infections
Some systemic viruses can also effect the liver. Name two
The types of viral hepatitis are really indistinguishable by clinical feature or routine lab test. Some pt may be really asymptomatic or simply look like they have the flu. Others may show jaundice. Lab marker is a marked elevated aminotransferase level. How do we find out the exact type of hepatitis?
antigen/antibody testing is really needed to find out the exact virus involved.
What is the route of infection in Hep A? Does it cause serious illness?
highly contagious and d/t fecal oral contamination and poor sanitary conditions. Hep A is usually self limiting and doesn’t cause chronic hepatitis or cirrhosis.
How long are people infectious w/Hep A?
The virus is shed in the stool for days prior to symptoms and the first 1-2 weeks of a clinical illness. But by 3 weeks people are no longer infectious.
How is Hep B transmitted?
usually transmitted paraenterally or transmitted during sexual contact
What are the risk factors for Hep B?
Risk factors: IV drug abuse, homosexual men, multiple sexual partners.
It can also be transmitted from mother to infant.
Because the blood products are screened they are much less likely to cause an infection from Hep B
How can you tell if someone has immunity to Hep B?
Immunity is conferred by the presence of hepatitis B surface antibodies and a large proportion of the population actually has these antibodies.
How is Hep C transmitted?
transmitted mainly through the parenteral route also.
60% of cases d/t IV drug use, another 15-20% d/t sexual contact and the remainder by maternal/infant and blood products.
Needle stick injuries are much less likely.
Again Hep C is now screened for in blood products so that’s really the cause for post transfusion hepatitis.
What are the signficant complicaitons of Acute Hep C infections?
Symptoms for 1-2 weeks before dark urine & jaundice appear
Bilirubin ↑’s for 10 – 14 days then ↓’s over next 14 – 28 days
AST & ALT start to ↓ just before jaundice peak
What % of patients with acute hepatitis (B and C) go on to develop chronic hepatitis
But in about 2-7% of patients w/Hep B and 60-75% of patients w/Hep C.
Of course chronic hepatitis (with B or C) puts the patient at risk for cirrhosis or a primary hepatocellular carcinoma but both of these could take years to develop.
What is the treatment for acute hepatitis?
Tx: symptomatic w/rest & good nutrition. If there is prolonged N/V then IV therapy may be needed and abstinence from alcohol is important. Liver transplant if permanent liver failure
How can we prevent acute hepatitis?
When will giving immunoglobin help in acute hepatitis?
If it’s given more than 14 days after exposure it really won’t help. Hep B exposed patients may benefit from Hep B immunoglobulin if it’s given within 24hours
Patients at high risk of Hep A infections should be vaccinated. Is it active or inactive and how long does it provide protection?
Hep A vaccine is inactivated Hep A and it produces a very effective antibody response and can provide protection for 10 years or longer
How long does the Hep B vaccine last?
5 years after vaccination, 20-30% of those vaccinated will lack protection because those antibody levels decline so booster is recommended.
Descrbe the type of acute hepatitis caused by the Cytomegalovirus
Describe the type of acute hepatitis caused by the Epstein-Barr Virus
Associated with infectious mono
Describe the drug-induced hepatitis from Tylenol
Acetaminophen overdose is the cause of profound hepatocellular necrosis.
Damage to liver cells is usually d/t toxic metabolites that get produced by the liver.
Ordinarily these metabolites would get conjugated with glutathione but when the dose of acetaminophen is too high the liver stores of glutathione are depleted and so what happens is those toxic metabolites accumulate and destroy the liver cells
What can we give to prevent the hepatotoxicity associated with Tylenol overdose?
There is a drug called anlcetylcystine if it’s given within 8hr of overdose of acetaminophen there is dramatic decreased risk of hepatotoxicity.
Sometimes hepatitis can occur from even normal doses of Tylenol. Why??
If the usual levels of glutathione are decreased (fasting or long term alcohol use) hepatotoxicity can occur from even normal doses of acetaminophen.
What is Halothane hepatitis
an immune mediated situation where certain IgG antibodies are present.
The antibodies in this case are microsomal proteins on the surface of the liver cells and these proteins on the surface of the liver cells have been modified by a metabolite of Halothane forming a neoantigen.
If thethe metabolites causing Halothane Hepatitis are also formed by Isoflurane and Desflurane, why don't we see it as much w/those volatiles?
so there can be a cross sensitivity but the reason we don’t see “halothane hepatitis” w/Isoflurane and Desflurane is that neither of those are metabolized to the same degree as Halothane. But if there is a genetically susceptible person there could be a cross sensitivity reaction.
What is the Bilirubin, AST & ALT, Alk. Phose, & Causes of Pre-hepatic dysfunction
What is the Bilirubin, AST & ALT, Alk. Phose, & Causes of Post-hepatic (Cholestatic) dysfunction
AST & ALT: normal -slihglty ↑
Alk. Phos.: markedly↑
Causes: Biliary tract stones & Sepsis
What is the normal ALT and AST and Alk Phos?
ALT: 10-35 U/L.
Alk. Phos: 42-136.
What is the normal Bilirubin? (direct, indirect and total)
What is the normal albumin?
Normal albumin is 3.5-5g/dL
Does overall hepatic function has the better prognostic indicator of AST and ALT???
Elevated bilirubin and PT are better prognostic indicators of overall hepatic function then either the ALT or AST.
Because in general severe liver disease is needed for those to be elevated.
What are the s/s of chronic hepatitis?
Similar to acute
Range on a continuum
What lab values do you see w/chronic hepatitis?
↑ AST & ALT
Bilirubin (Normal in chronic viral & ↑ in autoimmune)
When is chronic hepatitis usually defined?
represents long term elevation in LFTs w/inflammation seen on liver biopsy. Usually defined as when hepatitis has lasted for 6 months or longer
List as many causes for chronic hepatitis as you can think of
HBV & HCV
α 1 anti-trypsin deficiency
Primary biliary cirrhosis
Primary schlerosing cholangitis
What is Wilson's disease?
inherited disorder where there is too much copper in the body and then the copper will damage the liver along w/other organ systems.
Chronic hep B infection is present in about ___% of the worlds population. And about ____percent of those in the US are carriers of the antigen
For Hep B, Age at the time of the diagnosis is a significant determinant of the chronicity. __% of infected neonates become carriers
Who is more likely to be a carrier for Hep B, men or women?
What is the treatment for Hep B aimed at?
aimed at suppressing Hep B replication.
Drugs are some of the antiretroviral
What happens if a patient w/Hep B receives a liver transplant, can we stop the antiretrovirals?
No, If liver transplant is performed, Hep B will infect the transplanted liver in nearly all recipients.
So post transplant those antiretrovirals need to be continued along w/Hep B immunoglobulin.
Together those can decrease the rate of reinfection to about 10%.
Chronic hepatitis follows acute infection of Hep C in up to __% of patients. An estimated ___% of the US population are carriers of Hep C
How do we diagnose chronic hepatitis from Hep C?
Dx is based on lab data with persistent increase aminotransferase enzyme levels as well as antibodies to Hep C
When does a person w/Hep C develop cirrhosis and liver cancer?
The patient hx of these can cover 10 or more years with cirrhosis or liver cancer developing after 10-20 years.
When would we see a more rapid rate of progression of Hep C?
A more rapid rate progression to cirrhosis is more likely in the male patient over age 40 at the time of initial infection. Particularly if he consumes a significant amount of alcohol daily and has a coinfection with other liver viruses or w/HIV.
What kind of treatment is indicated in Hep C?
Interferon can be helpful in normalizing the aminotransferase enzymes and decreasing inflammation in about 40% of the patients but the response from a single drug therapy isn’t really sustained.
Combining interferon w/antiviral drugs will increase the % of patients having a sustained response.
What is the most common indication for liver transplantation???
Chronic hep C with liver failure is the most common indication for liver transplant.
Although the virus will infect the transplanted liver, the illness that results is usually mild and rarely progresses to liver failure.
Drug-induced chronic hepatitis can be seen with.....
methyldopa, trazadone, isoniazids (anti-TB), as well as the sulfonamides, acetominophen, ASA,