Liver disease

Question 1

Where does the liver get its blood supply from?

Answer 1

hepatic artery supplies about one third of the blood from the aorta; the portal vein
supplies the other two thirds from the digestive tract (stomach, intestine, pancreas) and spleen

Question 2

What is the function of the liver?

Answer 2

integral to most metabolic functions of the body and performs more than 500 tasks including
chemical detoxification, protein synthesis, and excretory functions.

Question 3

What is the function of the Hepatocytes?

Answer 3

basic workhorse cell, 80% of total liver parenchyma; form cords along arterial blood supply- Zones I-III

Question 4

What is the function of the Kupffer cells?

Answer 4

macrophages that filter and remove foreign substances

Question 5

What is the function of the Stellate cells?

Answer 5

Vitamin A storing cells, transform into fibrogenic myofibroblasts, make
collagen/scar, remodel extracellular matrix during injury.
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Question 6

What is the location and function of hepatic metabolic zone 1?

Answer 6

closest to portal triad, most resistant to effects of decreased blood supply or nutritional
deficiencies.

Question 7

What is the location and function of hepatic metabolic zone 3?

Answer 7

closest to terminal hepatic venule, this area is prone to anoxic injury and toxic insults.

Question 8

What is preferential expression of enzymes in the liver zone 1?

Answer 8

beta-oxidation, gluconeogenesis, cholesterol synthesis, bile formation and amino acid
metabolism.

Question 9

What is preferential expression of enzymes in the liver zone 3?

Answer 9

glycogen synthesis, glycolysis, ketogenesis, liponeogenesis, and drug metabolism.

Question 10

Generally liver disease presents as what? (cause)

Answer 10

hepatocellular injury, cholestatic (obstructive) injury, or a mixture of both.

Question 11

In hepatocellular injury (i.e. viral, alcohol-related), features of disease can include ?

Answer 11

fatty liver, inflammation (hepatitis) and cirrhosis.

Question 12

Typical findings at examination can include?

Answer 12

icterus, hepatomegaly, hepatic tenderness, splenomegaly, spider angiomata, and palmar erythema.

Question 13

Signs of advanced disease can include?

Answer 13

muscle-wasting, ascites, edema, dilated abdominal veins, mental confusion, stupor, and coma.

Question 14

In many cases, a diagnosis of liver disease can be made accurately by doing what?

Answer 14

with a careful history, physical exam, analysis of laboratory results. evaluation of liver tests can establish whether the pattern of abnormalities is hepatic, cholestatic, or mixed. duration of symptoms or abnormalities can indicate whether the disease is acute or chronic

Question 15

Acute injury that does not lead to liver failure should do what? Any disease or injury that chronically affects the liver will cause ?

Answer 15

completely resolve; fibrosis (scarring); this process will progress to cirrhosis.

Question 16

Cirrhosis follows from what and is characterized by what?

Answer 16

years of chronic liver injury; the presence of regenerative nodules that are surrounded by scar tissue

Question 17

Cirrhosis results from what? What is the leading cause in the US?

Answer 17

MOST COMMONLY: Hepatitis C virus, Alcohol, Hepatitis B virus, Nonalcoholic fatty liver disease, Drug-, Medication-induced
LESS COMMON: Autoimmune hepatitis, Primary biliary cirrhosis, Primary sclerosing cholangitis, Hemochromatosis, Wilson disease, Alpha-1 antitrypsin deficiency;
Hepatitis C w/ or w/o alcohol use

Question 18

Cirrhosis leads to what two major syndromes?

Answer 18

portal hypertension and hepatic failure.

Question 19

Decompensated liver function from cirrhosis is marked by the development of what?

Answer 19

jaundice, variceal

hemorrhage, ascites and/or encephalopathy.

Question 20

Cirrhosis can be diagnosed by a variety of tools including what?

Answer 20

laboratory tests, histology, imaging

studies (i.e. CT or ultrasound), or physical examination.Liver biopsy confirms the presence of cirrhosis

Question 21

What things might be present on a physical exam with a liver disease patient?


Answer 21

Jaundice, spider angioma, palmar erythema, caput medusa, hepatomegaly, splenomegaly, clubbing, ascites, asterixis, gynecomastia, testicular atrophy, temporal wasting, Dupuytren contracture

Question 22

What things might be present on a history with a liver disease patient?

Answer 22

fatigue, weight loss, decreased libido, inability to concentrate; 40% assymptomatic

Question 23

How is the Child-Turcotte-Pugh Score found?

Answer 23

Determined by assessing clinical complications of cirrhosis and laboratory abnormalities indicative of
liver dysfunction

Question 24

What is the Model for End-Stage Liver Disease (MELD) Score used for? Scale? How is it calculated?


Answer 24

The MELD score is a method for predicting 3-month survival, prioritizes candidacy for transplantation. numerical scale 6 to 40. use 3 lab results: bilirubin, NR, and CrCl
MELD = 3.78[Ln serum bilirubin (mg/dL)] + 11.2[Ln INR] + 9.57[Ln serum creatinine (mg/dL)] + 6.43

Question 25

What are the goal for management of cirrhosis?

Answer 25

Prevent additional liver damage, Slow or halt progression of liver disease and Manage cirrhotic complications,

Question 26

In cirrhosis how is additional liver damage prevented?

Answer 26

HAV vaccination, HBV vaccination, Pneumococcus vaccination, Influenza vaccination, Avoid or minimize hepatotoxic drugs and alcohol, Maintain normal BMI (avoid obesity)

Question 27

In cirrhosis how is progression of liver disease slowed or halted?

Answer 27

Abstinence from alcohol, regardless of underlying disease process: counsel or refer for treatment. Avoidance of hepatotoxic medications, Eradication of HCV infection, if possible, Suppression of HBV infection, if possible, Treatment of autoimmune hepatitis: can include prednisone or immunosuppressive agents

Question 28

In cirrhosis how are complications managed?

Answer 28

Prognosis strongly depends on elimination of the cause and the degree of complications already developed. Treatment options are dependent on stage of cirrhosis: compensated (asymptomatic) vs. decompensated.

Question 29

What is the difference between compensated and decompensated cirrhosis?

Answer 29

Cirrhosis can remain silent for many years prior to the development of a decompensating event. Decompensated cirrhosis is marked by the development of any of the following complications: jaundice, variceal hemorrhage, ascites or encephalopathy.

Question 30

What is the natural progression/history of cirrhosis?

Answer 30

Compensated without symptoms; no varices (very common); Compensated with presence of varices, but no bleeding; Decompensated with variceal hemorrhage; ascites; hepatic encephalopathy; Further decompensation: recurrence of hemorrhage; hepatorenal syndrome; jaundice; spontaneous bacterial peritonitis; Hepatocellular carcinoma

Question 31

Portal hypertension is the hemodynamic abnormality associated with the most severe complications of cirrhosis including what?

Answer 31

ascites, spontaneous bacterial peritonitis (SBP)

gastroesophageal variceal hemorrhage, hepatic encephalopathy

Question 32

Portal hypertension is related to an increase in blood pressure in the veins of the portal system
caused by?

Answer 32

compression in the liver leading to enlargement of the spleen and formation of collateral
veins.

Question 33

What are two key components of the pathogenesis of portal hypertension in cirrhotic patients?

Answer 33

increased portal blood flow and increased resistance to the passage of blood flow through the liver.

Question 34

How common is ascites in cirrhosis? How bad is it?

Answer 34

The most common complication of cirrhosis, 30% of patients with compensated cirrhosis develop ascites within 5 years, 2-year survival rate of patients with ascites is 50%,

Question 35

What is the make up of the fluid in ascites?

Answer 35

Ascitic fluid from cirrhosis has low total protein (1.1g/dl) serum-to-ascites albumin gradient (SAAG)

Question 36

What is the primary prophylaxis for ascites?

Answer 36

none recommended, other a than low-salt diet (1-2 g Na+/day)

Question 37

What are the treatment options for ascites?

Answer 37

Diuretics (e.g. spironolactone alone or plus furosemide), Start with spironolactone then add furosemide and sequentially increase as necessary and tolerated to maximum dosage of both, Avoid NSAIDs because of risk of hepatorenal syndrome, Patients with massive ascites may require large-volume (5-20 L) paracenteses, often with albumin supplementation.Refractory ascites may require placement of a transjugular intrahepatic portosystemic shunt (TIPS)

Question 38

What is Spontaneous Bacterial Peritonitis or SBP?

Answer 38

Bacterial infection of ascitic fluid that occurs in the absence of a traumatic source of infection (i.e. perforation),Source can be related to bacterial translocation from bowel leaking due to disease. Cirrhotic ascites has low complement and thus poor opsonic activity in the liver caused by improper macromolecular processing due to fibrotic obstruction.

Question 39

What is the primary prophylaxis for Spontaneous Bacterial Peritonitis (SBP)?

Answer 39

Fluoroquinolone may be initiated in the hospitalized patient with severe liver disease and renal dysfunction

Question 40

What are the treatment options for Spontaneous Bacterial Peritonitis (SBP)?

Answer 40

Third-generation cephalosporin, ampicillin/sulbactam, or fluoroquinolone, given IV for initial occurrence; avoid aminoglycosides

Question 41

How is SBP diagnosed?

Answer 41

Polymorphonuclear leukocyte (PMN) count of >250 cells/μL in the ascitic fluid, obtained via paracentesis Patients may be asymptomatic, may have very subtle clinical findings, or may have fever, abdominal pain, and altered mental status. 90% mortality if left untreated (30 day).

Question 42

Why should you be concerned about Variceal Hemorrhage/GI Bleeding in cirrhotic patients?

Answer 42

~25% of patients with cirrhosis and varices experience hemorrhage from gastroesophageal varices in the first year after diagnosis, 1/3 of those with varices will develop bleeding, The bleeding-related mortality is around 20% within a month of occurrence; common to screen cirrhotic patients for varices

Question 43

What factors predict recurrent GI bleeding?

Answer 43

the severity of cirrhosis (Child’s class), the size and location of varix, red wale signs, cherry red spots, hematocystic spots

Question 44

What is the primary prophylaxis for Variceal Hemorrhage/GI Bleeding?

Answer 44

Nonselective beta-blockers (not recommended until varices have been documented, ascites controlled) or endoscopic variceal ligation are recommended for prophylaxis in patients with medium or large varices, to prevent the first episode of variceal hemorrhage

Question 45

What are the treatment options for Variceal Hemorrhage/GI Bleeding?

Answer 45

When a variceal bleed occurs, immediate hospitalization and GI consultation are needed for treatment. After a variceal bleed, the combination of nonselective beta-blockers and endoscopic variceal ligation decrease the risk of another bleed

Question 46

What is Hepatic Encephalopathy?

Answer 46

A serious complication of liver disease involving alterations in mental status and cognitive function associated with liver failure. Variable abnormalities of neurological and psychiatric function, including insomnia, hypersomnia, irritability, confusion, disorientation, hyperactive deep tendon reflexes, and asterixis.

Question 47

What is the primary prophylaxis for Hepatic Encephalopathy? secondary?

Answer 47

1) none 2) None; once precipitating factors are eliminated, lactulose can be discontinued; in patients with chronic encephalopathy, chronic treatment with lactulose is warranted, Sedatives and narcotic analgesia should be avoided, Keep hydrated, constipation should be avoided

Question 48

What are the treatment options for Hepatic Encephalopathy?

Answer 48

Mainly consists of identification and treatment of precipitating factors: Electrolyte imbalance → hydration; Elimination of nitrogenous products from the gut thorough movements and colonic acidification→ Lactulose: start one dose until stooling, then titrate to 2-3 soft bowel movements per day, avoiding diarrhea (as it will lead to volume depletion and dehydration)
Rifaximin is an alternative for patients who cannot tolerate lactulose

Question 49

What is the hepatocytes main method of processing?

Answer 49

vesicular transport; reuse receptors

Question 50

What aspect of the hepatocytes normal functioning does Hep B and C take advantage of?

Answer 50

vesicular transport; bind to glycoproteins and are endocytosed into the cell; Hep C even used the vesicles to replicate

Question 51

What is the periportal region of the liver?

Answer 51

metabolic zone 1

Question 52

What is the perivenous region of the liver?

Answer 52

metabolic zone 3

Question 53

Provide an example of strict gene expression in the liver zones.

Answer 53

Carbamoyl phosphate in periportal and Gln Synth perivenous; both are for NH4, the second is a fail safe changing it to glutamate

Question 54

Give and example of gradient gene expression in the liver zones.

Answer 54

HMG coA in perportal; p450 and Alcohol Dehydrogenase perivenous

Question 55

Which plasma proteins is the liver a major site for synthesizing? How are they an indicator of disease?

Answer 55

albumin (<3.5 g/dL) and Prothrombin (carboxylation mediated by vit K, Prolonged PT or INR=PT/PTn)

Question 56

What does the liver do with cholesterol? inhibitors?

Answer 56

synthesize from acetyl coA this is inhibited by LDL uptake by the liver; degradation only happens in the liver, it is converted to bile salts

Question 57

How does the liver achieve detoxification?

Answer 57

Oxygenation-p450 enzymes, alter molecules via O2, free O2 radicals, end prod may be more dangerous than initial chem; Conjugation: sulfate, AA (glycine, taurine, glutamine, ornithine, arginine), glutathione, methylation, glucuronic acid, bile

Question 58

How does the liver regenerate?

Answer 58

mass is precisely regulated compared to body weight, synchronized waves of DNA replication, different cells regenerate at different rates and times, restore mass not structure, different cytokines and GFs involved in the different stages

Question 59

What are things that can be misleading in diagnosis of acute liver failure?

Answer 59

infrequency, young age, symptoms mild but biochemical derangement advanced, deterioration surprisingly rapid

Question 60

What are the at risk groups for acetaminophen liver toxicity?

Answer 60

alcoholics or abuser, enzyme inducing drugs (p450), lack of oral calories (short term starvation

Question 61

How is acute liver failure treated?

Answer 61

oral or IV source of cysteine for glutathione (N-acetylcysteine), 8-24 hours is best, up to 72 hours decreased mortality but never assume its too late

Question 62

what are the risk factors for alcoholic liver injury?

Answer 62

amount/duration, age, gender, ethnicity, Hep C or other