board review Flashcards
A 14-year-old youth has had intermittent periumbilical and lower abdominal pain, some bloating,
and increased flatus for 2 years. He denies a relationship of the pain to food or drink, and a milk-free
diet did not relieve his symptoms. He has had no fevers, diarrhea, constipation, bleeding, or other
systemic problems and his growth is normal. He eats a regular diet, including diet soft drinks and
sugar-free gum. His family is intact and he denies undue stress in his school or social life. He also
denies alcohol, drug use, or smoking. Physical examination is normal, including heme occult
negative rectal examination. Screening laboratory tests including complete blood count, ESR, liver
enzymes and amylase, and urinalysis are normal. Which one of the following would be the most
likely etiology of the abdominal complaints in this teenager?
A. lactose intolerance
B. excessive sorbitol intake
C. irritable bowel syndrome
D. teenage stresses
E. acid-peptic disease
Suggested answer: B or C. Sorbitol is a FODMAP (fermentable oligo-, di-, and
monosaccharides and polyols), metabolized by colonic bacteria to produce short chain fatty
acids and gas. Sorbitol is commonly found in diet soft drinks and sugar-free gum. When taken
in excess, sorbitol produces enough gas to produce abdominal pain and bloating as in this
patient. Sorbitol can also cause a persistent, osmotic diarrhea.
Irritable bowel syndrome, the most commonly diagnosed gastrointestinal condition, is diagnosed
by the presence of 3 things: i) chronic abdominal pain, ii) altered bowel habits (constipation or
diarrhea, which is may or may not be present in this patient), and iii) no organic cause. The
etiology of IBS in unclear; however, one hypothesis is that bacteria cause IBS, by fermenting
FODMAPs in the colon. FODMAPs have been shown to produce IBS symptoms in clinical
trials. Treatment for IBS is broad, and includes a strong physician-patient relationship,
avoiding certain foods (lactose, allergens, gluten), anti-spasmodics, anti-depressants, antidiarrheal agents, and/or antibiotics.
This patient does not have lactose intolerance, as a milk-free diet did not relieve his symptoms.
He should resume drinking milk, or at least receive calcium and Vitamin D supplements to
support growth. In addition, the patient does not report excessive stress, and does not have
typical GERD symptoms.
A 9-year-old girl has been losing hair for about 2 years and now presents with a large mass in her
epigastrum. Her parents separated about 3 years ago. The patient and her siblings have been
spending part of each week at each parent’s home. A plain film of the abdomen reveals a large
mass in the stomach. Endoscopy reveals a trichobezoar. What do you now recommend to the
family?
A. administer meat tenderizer orally
B. endoscopic removal of bezoar under anesthesia
C. abdominal CT scan to rule out gastric tumor
D. surgical consultation for removal of bezoar
E. reassurance that the bezoar will pass
Suggested answer: D. Trichobezoars usually occur in young women with psychiatric disorders,
and in some cases may extend through the small bowel and even cecum (Rapunzel syndrome).
Phytobezoars (from vegetable matter) are responsive to enzymatic dissolution, including
cellulase, papain, and carbonated soda. Trichobezoars are resistant to enzymes and must be
removed manually. Endoscopy can be attempted but often fails, with the endoscopic tools
becoming snared in the strands of hair. Surgical removal is more effective. All patients should
receive psychiatric therapy to prevent the problem from reoccurring.
Among the hepatitis viruses, the hepatitis B virus (HBV) is unique because:
A. liver injury is mediated through the immune system
B. the presence of antibodies to HBV indicates protective immunity
C. it has similarities to human retroviruses because it is a DNA virus which replicates
through an RNA intermediate
D. it is the only agent to cause fulminant hepatic failure
E. it has a glycoprotein coat enclosing a viral nucleocapsid
Suggested answer: C. HBV is a DNA virus that enters the hepatocyte nucleus and is read by
host-cell machinery to make RNA particles. The RNA particles in turn are exported to the
cytoplasm, where HBV-encoded reverse transcriptase converts them to new viral DNA particles.
Infection can be acute and cause fulminant hepatic failure; however, chronic infections
characterized by a series of stages are more common. First, in the “immune tolerant” phase,
the host allows HBV infection and replication as seen by high HBV DNA levels and HBeAg
positivity. Second, in the “immune clearance” phase, the host mounts an immune response
against infected hepatocytes, signified by the appearance of anti-HBe, disappearance of HBe-Ag,
transaminase elevation, and hepatitis symptoms. In some cases, the host clears the virus
completely (anti-HBs appears, HBsAg disappears); in other cases, the virus becomes latent and
can reactivate/stimulate the “immune clearance” phase at unpredictable times. The virus has a
glycoprotein envelop enclosing a proteinaceous nucleocapsid.
HAV is an RNA virus that never enters the nucleus; rather, in the cytoplasm, it makes more
particles using its own RNA-dependent RNA polymerase. Infections are acute and can cause
fulminant hepatic failure. Infections have a biphasic pattern, first with viral replication (akin to
the HBV “immune tolerant” phase”) quickly followed by immune attack of virus and cells
harboring the virus (akin to the HBV “immune clearance” phase, and characterized by
appearance of anti-Hep A IgM and hepatitis symptoms). The virus does not have an envelope,
but does have a proteinaceous nucleocapsid surrounding the RNA.
HCV is an RNA virus like HAV but has an envelope. It also never enters the nucleus, but rather
enters the cytoplasm, takes over the cell’s ribosomal machinery, and converts the cell into a
factory producing viral proteins that generate more viral nucleic acid and particles. Viral
particles then bud off the cells (using the cell’s plasma membrane for an envelope) and infect
other cells. Acute infections are mild or even asymptomatic, and fulminant hepatic failure is
rare. Chronic infections are more common, and occur when the host cannot completely clear
the infection. This long-term, low-level battle between host and virus leads to liver
inflammation, cirrhosis, and hepatocellular carcinoma.
HDV is an RNA virus with an envelope like HCV; however, the envelope has HBsAg, making
HDV replication possible only in cells also infected with HBV. HDV enters the nucleus, and
host-cell RNA polymerases use the original HDV strand to make more RNA particles. Acutely,
HDV is thought to cause cytopathic damage to hepatocytes and may be confused with HBV
reactivation (see above). Fulminant hepatic failure is possible. Chronically, the host immune
response to HDV infected cells causes hepatocyte damage.
HEV is an RNA virus without an envelope, similar to HAV. The life cycle is less wellunderstood, but HEV appears to never enter the nucleus (similar to HAV). Instead, in the
cytoplasm, the virus makes more particles using its own RNA-dependent RNA polymerase.
Infections are usually acute and can cause fulminant hepatic failure. Chronic infections have
only been reported in solid-organ recipients taking post-transplant immunosuppression.
Common routes of the spread of hepatitis A virus include all of the following except:
A. consumption of contaminated water or food
B. close personal contact
C. infants in daycare centers
D. homosexual men by sexual contact
E. transfusion of packed red blood cells
Suggested answer: E. Hepatitis A is shed in bile, found in stools, and spread fecal-orally.
Hence, it can be spread through consumption of contaminated water/food, close personal
contact (without proper hand-washing), infants in close proximity in a day care, and other close
contact such as anal-oral sexual contact. Interestingly, infants that acquire HAV infection have
a less severe course, perhaps because of a less developed immune system. HAV is not spread
through blood transfusions.
Serological changes associated with being a healthy carrier of the hepatitis B virus are:
A. HBsAg positive, HBeAg positive, HBV DNA negative by hybridization assay, with
normal serum aminotransferases
B. HBsAg positive, HBV DNA negative by hybridization assay, anti-HBe positive, with
normal serum aminotransferases
C. HBsAg negative, anti-HBs positive, anti-HBe positive
D. HBsAg negative, anti-HBs negative, anti-HBe positive
E. HBsAg positive, HBV DNA positive by hybridization assay, HBeAg negative, with only
slightly elevated serum aminotransferases
Suggested answer: E. Inactive carries are those who were once infected with Hepatitis B and
mounted a successful immune response against it. During the infection or “immune tolerant”
phase, these patients had HBV antigens and DNA in their serum (HBsAg positive, HBeAg
positive, HBV DNA virus positive) but have not yet mounted an immune response (anti-HBe
negative as well as anti-HBs negative). During the immune response or “immune clearance”
phase, these patients developed antibodies against the virus (anti-HBe positive) as well as a
clinical picture of hepatitis (elevated transaminases). Their immune response is effective but not
complete, rendering them carriers with evidence of the virus still present (HBsAg positive, HBV
DNA hybridization positive) but also evidence of a successful response (anti-HBe positive
causing HBeAg negativity). Carriers may also have slightly elevated aminotransferases. Had
their immune response been complete, the patients would be cured of the disease and be antiHBs positive, HBsAg negative, anti-HBe positive, HBeAg negative, and HBV DNA negative.
All of the following statements about hepatitis E are true, except:
A. outbreaks of hepatitis E tend to be very large because of the high rate of secondary (caseto-case) spread
B. cases of hepatitis E in the United States are rare
C. infection with hepatitis E virus (HEV) in pregnancy is associated with high mortality rate
D. anti-HEV appears to be protective, and prospects for developing a vaccine are good
E. HEV is not closely related in structure or function to any of the other viral hepatitis
agents
Suggested answer: A. While the seroprevalence of HEV is ~20% in the US, symptomatic HEV
infection is rare (perhaps because most infections may be with the less virulent genotype 3).
HEV is acquired through contaminated water and rarely spreads person-to-person, making it
less readily transmissible than HAV. Following HEV infections, humans develop anti-HEV IgM
and then anti-HEV IgG. There are no HEV vaccines readily available yet, though some are
being developed. HEV has a unique genome and structure and is the only member of the genus
hepevirus in the family Hepeviridae.
HEV is most dangerous during pregnancy. For unclear reasons, women infected in the third
trimester have an increased risk of hepatic failure and mortality (15-25% mortality rate). This
may because the virus replicates faster in the pregnancy state. Furthermore, infants born to
infected mothers are also at risk, with some presenting with massive hepatic necrosis shortly
after birth.
Recognized complications of acute hepatitis A include all of the following except: A. fulminant hepatic failure B. relapsing hepatitis C C. chronic hepatitis D. cholestatic hepatitis E. triggering autoimmune hepatitis
Suggested answer: B. HAV most commonly causes an acute, self-resolving hepatitis. However,
it has been associated with a variety of other presentations: i) fulminant hepatic failure (rare);
ii) relapsing, chronic hepatitis characterized by HAV-caused hepatitis interspersed between long
periods without symptoms (prognosis is excellent, with no reports of cirrhosis or chronic liver
disease); iii) cholestatic hepatitis characterized by prolonged jaundice, itching, and laboratory
abnormalities, which eventually self-resolves with supportive care; and iv) triggering of
autoimmune hepatitis, which develops months after the initial HAV infection.
A 45-year-old woman is undergoing treatment for chronic hepatitis C with the combination of
interferon (3 three times a week) and ribavirin (1000 mg per day). Prior to therapy she was
found to have cirrhosis but there was no evidence of hepatic decompensation. Her baseline blood
count was hemoglobin 13.9 g/dL, MCV 89, total white cell count 4200/mm3
, platelet count
92,000/mm3
. After 6 weeks of therapy, her blood count was hemoglobin 9.9 g/dL, MCV 102,
total white cell count 2500/mm3
, platelet count 47,000/mm3
. The best course of action is:
A. decrease the dose of ribavirin to 600 mg/day
B. decrease the dose of interferon to 1.5 three times a week
C. administer recombinant human erythropoietin
D. decrease the dose of both ribavirin (to 600 mg/day) and interferon (to 1.5 three times a
week)
E. check serum levels of folate and vitamin B12 and correct if deficient
Suggested answer: D. This patient is being treated with interferon and ribivarin, which implies
she has either genotype 2, 3, or 4 (genotype 1 is treated with interferon, ribivarin, and a protease
inhibitor). Interferon strengthens the innate and adaptive immune response, whereas ribivarin is
a nucleoside analog.
80% of patients taking interferon and ribivarin have side-effects. Anemia usually appears in the
first 12 weeks, caused by ribivarin-induced hemolysis (ribivarin is concentrated in erythrocytes
leading to oxidative damage) and interferon-related bone marrow suppression to blunt a
compensatory response. Neutropenia and thrombocytopenia occur soon after treatment
initiation and are due to interferon-related bone marrow suppression. Ribivarin dose reduction
would treat the anemia, whereas Interferon dose reduction would treat the thrombocytopenia.
Erythropoietin is another medication that has been shown to improve the anemia, possibly
without needing to reduce the ribivarin dose.
An 18-year-old Asian woman is being treated for hepatitis B. Prior to therapy she was found to
have ALT 198 U/L, AST 91 U/L, normal bilirubin, albumin, and prothrombin time. Liver biopsy
results showed chronic hepatitis B, grade 3, stage 3. After 12 weeks of therapy, serum ALT is
found to have increased to 1,082 U/L, bilirubin 2.1 mg/dL but albumin and prothrombin time
remain normal. Apart from some fatigue, the patient is tolerating interferon well. The best course
of action is:
A. check for antinuclear antibodies and total immunoglobulin level in serum and consider
instituting corticosteroid therapy
B. stop interferon
C. recheck lab work again in 2 weeks time
D. add lamivudine to the regimen
E. ask the patient to skip three scheduled doses of interferon
Suggested answer: C. Interferon and the antiviral lamivudine are used to treat HBV infection in
children. Interferon is dosed for 16 weeks, has numerous side effects, and leads to serological
conversion (presence of anti-HBe positive and HBeAg negative) in 40% (genotypes A and B) to
5-15% (genotypes C and D) cases. Lamivudine is taken indefinitely and has similar rates of
seroconversion after 2 years (~30-35%). Lamivudine, however, induces viral resistance, with
rates greater than 60% reported after 3 years of use.
This patient is taking interferon. Interferon causes a rise in AST/ALT in 30-40% of cases, likely
because it stimulates the immune system to destroy infected hepatocytes. Hence, this rise is a
sign the medication is working. Had the patient been taking lamivudine, a rise in AST/ALT could
also signify development of viral resistance. Interferon does induce autoantibodies that can be
symptomatic (i.e. hypothyroidism, hyperthyroidism) but this is less common. Interferon should
not be stopped, because the patient’s fatigue is only mild. Adding lamivudine to the interferon
regimen may decrease viral load faster, but has not been shown to produce better virological
outcomes after the 16 week course has finished. (On the other hand, combination therapy with
lamivudine plus interferon, versus lamivudine alone, may prevent development of viral
resistance.)
All of the following are primary cellular components of the immune system and the gut mucosa except: A. Peyer's patches B. lamina propria lymphocytes C. intrapithelial lymphocytes D. IgG-secreting B lymphocytes E. IgA-secreting B lymphocytes
Suggested answer: D. The gut is the largest lymphoid organ in the body. Specialized epithelial
cells, called M cells, sit above Peyer’s patches and sense luminal antigens. The M cells then
stimulate naïve B and T cells in the Peyer’s patches. The naïve cells undergo a long maturation
process, during which they take a long circular course to eventually return to the gut mucosa
(Peyer’s patches regional lymph nodes lymphatics thoracic duct systemic circulation
exit in the lamina propria). In the lamina propria, they reside and perform their immune
surveillance functions. In addition, special memory T-cells called intraepithelial lymphocytes
are anchored to the epithelial layer. They respond to a subset of luminal antigens, and secrete
cytokines to mediate the inflammatory response.
B cells that mature into plasma cells ultimately residing in the lamina propria have special
functions. They mainly secrete IgA2 and very little IgM and IgE, but virtually no IgG. IgA2
differs from the IgA1 made by plasma cells in the circulation. IgA2 molecules are dimeric and
secreted into the luminal space only after transiting through epithelial cells (via endocytosis
followed by exocytosis). Furthermore, IgA2 molecules are essentially non-inflammatory because
they bind antigens but do not activate complement. As a result, IgA2 molecules neutralize
antigens without triggering excessive inflammation to the countless number of gut antigens.
Cells from intestinal lymphoid tissues migrate to all of the following immune tissues except:
A. gastrointestinal mucosal immune tissues
B. pulmonary mucosal immune tissues
C. genitourinary tract
D. lactating mammary glands
E. skin
Suggested answer: E. The “common mucosal immune system” refers to the interconnected
mucosal organs that house IgA2 secreting plasma cells (which initially started as naïve B cells in
Peyer’s patches). These mucosal organs include the lamina propria of the small intestine, the
salivary and lacrimal glands, the lactating mammary glands, the genitourinary tract, and the
lungs. Migration to these areas is mediated by specific cell adhesion molecules.
Which one of the following most accurately reflects the epidemiologic features of inflammatory
bowel disease?
A. the prevalence is approximately 100 cases per 100,000 general population
B. the prevalence is approximately 1,000 cases per 100,000 general population
C. non-Jews are more likely to develop Crohn’s disease than Jews
D. people who smoke are less likely to get Crohn’s disease
E. people who smoke are more likely to get ulcerative colitis
Suggested answer: A. The epidemiology of inflammatory bowel disease has been well studied.
In North America, UC has prevalence of 27-246 per 100,000 persons, and Crohn disease has a
prevalence of 26-201 per 100,000 persons. There is a negative correlation between smoking and
UC, and a positive correlation between smoking and Crohn disease recurrence. People of
Jewish descent have a higher risk of developing Crohn disease compared to non-Jews,
highlighting the partly-genetic etiology of the disease.
Which one of the following extraintestinal manifestations of inflammatory bowel disease do not parallel the course of intestinal inflammation and do not improve in parallel with improvement in intestinal symptoms? A. peripheral arthritis B. apthous ulcers C. spondylitis and sacroiliitis D. erythema nodosum E. uveitis and iritis
Suggested answer: C. Arthritis is the most common extra-intestinal complications of IBD.
Peripheral arthritis usually involves large joints, does not cause synovial destruction, and
parallels the course of intestinal symptoms. Central axial arthritis, such as ankylosing
spondylitis (characterized by back and progressive spinal stiffness) is similar to primary
sclerosing cholangitis in that it does not follow the course of intestinal disease. Treatments for
axial arthritis include NSAIDs (despite concern for inducing worsening intestinal inflammation),
methotrexate, sulfasalazine, and/or anti-TNF therapy. Apthous ulcers, erythema nodosum,
uveitis, and iritis often (but not always) parallel intestinal disease.
All of the following urinary tract complications may occur as a consequence of Crohn’s disease
except:
A. calcium oxalate renal stones
B. calcium phosphate renal stones
C. uric acid renal stones
D. ureteral obstruction due to retroperitoneal fibrosis
E. fistulous communication between the terminal ileum and the bladder
Suggested answer: B. There are two general mechanism by which Crohn disease affects the
renal system. First, transmural inflammation can affect the underlying ureters, causing
occlusion usually on the right side and hydronephrosis. Inflammation can also create fistulas
between inflamed bowel and the bladder, promoting cystitis and urinary tract infections.
Second, Crohn disease is associated with calcium oxalate and uric acid renal stones. Calcium
oxalate stones form when the ileum is affected, preventing proper absorption of fats.
Unabsorbed long-chain fatty acids compete with the insoluble calcium oxalate for calcium.
Without calcium, oxalate binds sodium, becomes soluble, is absorbed by the colon (“enteric
hyperoxaluria”), and eventually re-precipitates as calcium oxalate stones when excreted in the
urine. Calcium is an effective treatment. Uric acid stones form secondary to bicarbonate loss
with diarrhea. With low serum bicarbonate, the kidneys excrete acid in compensation. Uric
acid, which is soluble in alkalotic conditions, precipitates as stones in the low pH urine.
All of the following statements regarding the release of mesalamine (5-aminosalicylate) by the
following delivery systems are true except:
A. the dose form Pentasa releases throughout the small and large intestine beginning in the
duodenum and continuing through to the rectum
B. the dose form Asacol releases beginning in the terminal ileum and cecum and continuing
through to the rectum
C. the dose form olsalazine (Dipentum) releases throughout the colon beginning in the cecum
and extending to the rectum
D. mesalamine administered as a Rowasa suppository extends to the left colon and splenic
flexure
E. no exception
Suggested answer: A. Sulfasalazine is used to treat topical inflammatory bowel disease. It is
metabolized by colonic bacteria into two components: 5-ASA, which has anti-inflammatory
properties, and sulfapyridine, which has anti-bacterial products. More recently 5-ASA products
alone have been developed, because many patients are intolerant to the sulfapyridine component.
Sulfasalazine and 5-ASA behave similarly in trials, suggesting that the sulfapyridine anti-bacterial
function has little significance.
Because ingested 5-ASA is rapidly absorbed in the jejunum, enemas have been used to deliver
medication directly to the colon. In addition, two delayed release preparations have been made.
The first involves coating 5-ASA with resins or microgranules, which dissolve and release 5-ASA in
settings of pH>7 (distal small bowel and colon). Pentasa and Asacol have this coating. The second
involves dimerizing 5-ASA, so that it is only released after bacterial cleavage (in the colon).
Olsalazine (Dipentum) is an example of this dimer form. Importantly, neither delivery system has
proven more efficacious over the other.
