•The answer is A.

The most common and most characteristic symptom of liver disease is fatigue. Unfortunately, it
is also very nonspecific with little specific diagnostic utility. The fatigue in liver disease seems to
improve in the morning and worsen throughout the day, but it can be intermittent. Jaundice is
the hallmark of liver disease and is much more specific. Jaundice, however, is typically a sign of
more advanced disease. Itching is also typically a symptom of more advanced disease and is
more common in cholestatic causes of liver disease. Nausea often occurs in severe disease and
can be accompanied by vomiting. Right upper quadrant pain is a less common symptom and
indicates stretching of the liver capsule.
•The answer is B.
Women are more susceptible to the effects of alcohol on the liver. On average,
drinking about two drinks daily can lead to chronic liver disease in women, whereas in
men it is about three drinks daily. In individuals with alcoholic cirrhosis, the average
daily alcohol intake is usually much higher, however, and heavy drinking for more than
10 years is typical before the onset of liver disease.
•The answer is E.
In most instances, patients with any form of acute viral hepatitis do not succumb to fulminant liver failure.
However, pregnant women are highly susceptible to fulminant hepatic failure in the setting of acute
hepatitis E infection. This RNA virus is an enteric virus that is endemic in India, Asia, Africa, the Middle East,
and Central America, and is spread via contaminated water supplies. Person-to-person spread is rare.
Generally, the clinical course of hepatitis E infection is mild, and the rate of fulminant hepatitis is only 1–2%.
However, in pregnant women, this is as high as 10–20%. For hepatitis A and C, the rate of fulminant hepatic
failure is about 0.1% or less. It is slightly higher for hepatitis B at around 0.1–1%. Hepatitis D occurs as a
coinfection with hepatitis B virus. When the two viruses are acquired simultaneously, the rate of fulminant
hepatitis is about 5% or less. When hepatitis D is acquired in the setting of chronic hepatitis B infection, this
number rises to 20%.
•The answer is A.
The liver is the primary site for the metabolism of many drugs and as such is susceptible to injury related to drugs and toxins. Indeed, the most
common cause of acute hepatic failure is drug-induced liver injury. In general, it is useful to think of chemical hepatotoxicity within two broad
categories: direct toxic effects and idiosyncratic reactions. Drugs or toxins that cause a direct toxic effect on the liver are either poisons
themselves or are metabolized to toxic substances. With agents that cause a direct toxic effect on hepatocytes, there is a predictable, dose-
related pattern of injury, and the time to effect is relatively short. The most common drug or toxin causing direct hepatocyte toxicity is
acetaminophen. In therapeutic doses, acetaminophen does not cause liver injury. However, in higher doses, one of the metabolites of
acetaminophen, N-acetyl-p-benzoquinone-imine (NAPQI), can overwhelm the glutathione stores of the liver that are necessary to convert NAPQI
to a nontoxic metabolite and lead to hepatocyte necrosis. Other medications or toxins that cause direct hepatocyte injury are carbon tet-
rachloride, trichloroethylene, tetracycline, and the Amanita phalloides mushroom. More commonly known as the deathcap mushroom, ingestion
of a single mushroom can contain enough hepatotoxin to be lethal. Idiosyncratic reactions are infrequent and unpredictable. There is no dose
dependency, and the timing of hepatic injury has little association with the duration of drug treatment. Many drugs produce idiosyncratic
reactions, and often it is difficult to known when an idiosyncratic reaction will lead to more serious liver failure. Often, mild increases in
transaminase levels will occur, but over time adaptation leads to a return of liver enzymes to normal levels. In other instances, idiosyncratic
reactions can lead to fulminant hepatic failure. Although rare, serious hepatic reactions can lead to medications being removed from the market.
It is now recognized that many idiosyncratic reactions are related to metabolites leading to liver injury. However, it is likely that individual genetic
variations in liver metabolism are the primary cause, and these are not predictable effects of the drug given our current state of knowledge.
Common medications that can lead to idiosyncratic drug reactions include halothane, isothane, isoniazid, HMG-CoA reductase inhibitors, and
chlorpromazine.
•The answer is D.
It is important to understand the patterns of laboratory abnormalities that indicate liver disease is present. One way to
consider laboratory evaluation of liver disease is to consider three general categories of tests: tests based on excretory
function of the liver, tests of biosynthetic activity of the liver, and coagulation factors. The most common tests of liver
function fall under the category of tests based on the detoxification and excretory function of the liver. These include serum
bilirubin, urine bilirubin, ammonia, and enzyme levels. Bilirubin can exist as a conjugated and an unconjugated form. The
unconjugated form is often referred to as the indirect fraction. Elevations in the unconjugated form of bilirubin are not
related to liver disease, but are most commonly seen in hemolysis and a number of benign genetic conditions such as
Gilbert’s syndrome. In contrast, conjugated hyperbilirubinemia almost always indicates disease of the liver or biliary tract.
Conjugated bilirubin is water soluble and is excreted in the urine, but unconjugated bilirubin is not. Rather, it binds to
albumin in the blood. Therefore, bilirubinuria implies liver disease as well. Among the serum enzymes, it is useful to
consider those that are associated with hepatocellular injury or those that reflect cholestasis. Alanine and aspartate
aminotransferases are the primary enzymes that indicate hepatocyte injury. Alkaline phosphatase is the most common
enzyme elevated in cholestasis, but bone disease also causes increased alkaline phosphatase. In some cases, one needs
additional information to determine if the alkaline phosphatase is liver or bone in origin. Other tests that would be elevated
in cholestatic liver disease are 5′-nucleotidase and γ-glutamyl transferase. The primary test of synthetic function is
measurement of serum albumin. Coagulation factors can be directly measured, but impaired production of coagulation
factors in liver disease is primarily inferred from elevations in prothrombin time.
•The answer is C.
Gallstones are very common, particularly in Western countries. Cholesterol stones are responsible for 80%
of cases of cholelithiasis; pigment stones account for the remaining 20%. Cholesterol is essentially water
insoluble. Stone formation occurs in the setting of factors that upset cholesterol balance. Obesity,
cholesterol-rich diets, high-calorie diets, and certain medications affect the biliary secretion of cholesterol.
Intrinsic genetic mutations in certain populations may affect the processing and secretion of cholesterol in
the liver. Pregnancy results in both an increase in cholesterol saturation during the third trimester and
changes in gallbladder contractility. Pigment stones are increased in patients with chronic hemolysis,
cirrhosis, Gilbert’s syndrome, and disruptions in the enterohepatic circulation. Although rapid weight loss
and low-calorie diets are associated with gallstones, there is no evidence that a high-protein diet confers an
added risk of cholelithiasis.
•The answer is A.
The innate immune system is phylogenetically the oldest form of immunologic defense system,
inherited from invertebrates. This defense system uses germ line–encoded proteins to recognize
pathogen-associated molecular patterns. Cells of the innate immune system include macrophages,
dendritic cells, and natural killer lymphocytes. The critical components of the innate immune system
include recognition by germ line–encoded host molecules, recognition of key microbe virulence
factors but not recognition of self molecules, and nonrecognition of benign foreign molecules or
microbes. Adaptive immunity is found only in vertebrate animals and is based on the generation of
antigen receptors on T and B lymphocytes by gene rearrangements, such that individual T or B
cells express unique antigen receptors on their surface capable of recognizing diverse
environmental antigens
•The answer is A.
Antinuclear antibodies are nearly ubiquitous in patients with systemic lupus
erythematosus, with demonstration in 90% of affected patients. There are many other
antibodies that can be demonstrated. The next most common antibodies are anti-
dsDNA and anti-histone. Anti-dsDNA is very specific to SLE and may correlate with
disease activity, nephritis, and vasculitis. Antihistone is more frequent in drug-induced
SLE. Antiphospholipid antibodies can be demonstrated in about half of affected
patients, while the remainder is present in less than half of SLE cases.
•The answer is E.

Once the disease process of rheumatoid arthritis is established, the most common joints of
involvement are the wrists, metacarpophalangeal joints, and proximal interphalangeal joints.
Distal interphalangeal joint involvement is rarely due to rheumatoid arthritis and more often
due to coexisting osteoarthritis.
•The answer is A.
Joint imaging is a critical tool for both the diagnosis and monitoring of disease status in RA. Plain
radiographs, because of their ready availability and ease of film comparison, are most
commonly ordered. The earliest clinical sign of RA is juxtaarticular osteopenia, though this may
be difficult to appreciate on newer, digitized films. Other findings include soft-tissue swelling,
symmetric joint space loss, and subchondral erosions most frequently in the wrists,
metacarpophalangeal, and proximal interphalangeal joints, and the metatarsophalangeal joint.