Transcript C. - UCLA Department of Surgery

Hyperacute rejection is caused by
A. Preformed antibodies
B. B-cell–generated antidonor antibodies
C. T-cell–mediated allorejection
D. Nonimmune mechanism
Answer A.
Explanation: Hyperacute rejection, which usually occurs within minutes
after the transplanted organ is reperfused, is due to the presence of
preformed antibodies in the recipient, antibodies that are specific to the
donor. These antibodies may be directed against the donor's HLA antigens
or they may be anti-ABO blood group antibodies. Either way, they bind to
the vascular endothelium in the graft and activate the complement
cascade, leading to platelet activation and to diffuse intravascular
coagulation. The result is a swollen, darkened graft, which undergoes
ischemic necrosis. This type of rejection is generally not reversible, so
prevention is key.
Prevention is best done by making sure the graft is ABO-compatible and
by performing a pretransplant cross-match. The cross-match is an in vitro
test that involves mixing the donor's cells with the recipient's serum to look
for evidence of donor cell destruction by recipient antibodies. A positive
cross-match indicates the presence of preformed antibodies in the
recipient that are specific to the donor, thus a high risk of hyperacute
rejection if the transplant is performed. (See Schwartz 8th ed., Chapter 10,
Transplant Immunology.)
The mechanism of action of azathioprine is
A. Inhibition of calcineurin
B. Interference with DNA synthesis
C. Binding of FK-506 binding proteins
D. Inhibition of P7056 kinase
Answer B.
Explanation: Azathioprine (AZA) acts late in the immune process,
affecting the cell cycle by interfering with DNA synthesis, thus suppressing
proliferation of activated B and T lymphocytes. AZA is valuable in
preventing the onset of acute rejection, but is not effective in the treatment
of rejection episodes themselves.
Cyclosporine binds with its cytoplasmic receptor protein, cyclophilin, which
subsequently inhibits the activity of calcineurin. Doing so impairs
expression of several critical T-cell activation genes, the most important
being for interleukin-2 (IL-2). As a result, T-cell activation is suppressed.
The metabolism of cyclosporine is via the cytochrome P450 system,
therefore several drug interactions are possible. Inducers of P450 such as
phenytoin decrease blood levels; drugs such as erythromycin, cimetidine,
ketoconazole, and fluconazole increase them.
Tacrolimus, like cyclosporine, is a calcineurin inhibitor and has a very
similar mechanism of action. Cyclosporine acts by binding cyclophilins,
while tacrolimus acts by binding FK506-binding proteins (FKBPs). The
tacrolimus-FKBP complex inhibits the enzyme calcineurin, which is
essential for activating transcription factors in response to the rise in
intracellular calcium seen with stimulation of the T-cell receptor (TCR). The
Lymphoceles occur how long after a renal
transplant?
A. Within 48 h
B. ~1 week after surgery
C. 2–4 weeks after surgery
D. 3 months after surgery
Answer C.
Explanation: The reported incidence of lymphoceles (fluid collections of
lymph that generally result from cut lymphatic vessels in the recipient) is
0.6 to 18%. Lymphoceles usually do not occur until at least two weeks
posttransplant. Symptoms are generally related to the mass effect and
compression of nearby structures (e.g., ureter, iliac vein, allograft renal
artery), and patients develop hypertension, unilateral leg swelling on the
side of the transplant, and elevated serum creatinine. Ultrasound is used to
confirm a fluid collection, although percutaneous aspiration may be
necessary to exclude presence of other collections such as urinomas,
hematomas, or abscesses. The standard surgical treatment is creation of a
peritoneal window to allow for drainage of the lymphatic fluid into the
peritoneal cavity where it can be absorbed. Either a laparoscopic or an
open approach may be used. Another option is percutaneous insertion of a
drainage catheter, with or without sclerotherapy; however, it is associated
with some risk of recurrence or infection. (See Schwartz 8th ed., Chapter
10, Kidney Transplantaion.)
Which of the following is NOT a side effect of
cyclosporine?
A. Interstitial fibrosis of the renal parenchyma
B. Gingival hyperplasia
C. Headache
D. Pancreatitis
Answer D
Explanation: Adverse effects of cyclosporine can be classified as renal or
nonrenal. Nephrotoxicity is the most important and troubling adverse effect
of cyclosporine. Cyclosporine has a vasoconstrictor effect on the renal
vasculature. This vasoconstriction (likely a transient, reversible, and dosedependent phenomenon) may cause early posttransplant graft dysfunction
or may exaggerate existing poor graft function. Also, long-term
cyclosporine use may result in interstitial fibrosis of the renal parenchyma,
coupled with arteriolar lesions. The exact mechanism is unknown, but
renal failure may eventually result.
A number of nonrenal side effects may also be seen with the use of
cyclosporine. Cosmetic complications, most commonly hirsutism and
gingival hyperplasia, may result in considerable distress, possibly leading
to noncompliant behavior, especially in adolescents and women. Several
neurologic complications, including headaches, tremor, and seizures, also
have been reported. Other nonrenal side effects include hyperlipidemia,
hepatotoxicity, and hyperuricemia. (See Schwartz 8th ed., Chapter 10,
Clinical Immunosuppression.)
The 5-year graft survival rate after renal
transplantation is
A. 35–40%
B. 50–55%
C. 75–80%
D. 90–95%
Answer C.
Explanation: The incidence of acute rejection has declined steadily since
the early 1990s. Most centers now report acute rejection rates of 10 to
20% at 1 year posttransplant. This decline has been a major factor in the
improvement in graft survival rates, which are now about 75 to 80% at 5
years and 60 to 65% at 10 years posttransplant for all kidney recipients.
Currently, the most common cause of graft loss is recipient death (usually
from cardiovascular causes) with a functioning graft. The second most
common cause is chronic allograft nephropathy. Characterized by a slow,
unrelenting deterioration of graft function, it likely has multiple causes (both
immunologic and nonimmunologic). The graft failure rate due to surgical
technique has remained at about 2%. (See Schwartz 8th ed., Chapter 10,
Kidney Transplantation.)
All of the following are absolute
contraindications in considering a candidate
for orthotopic cardiac transplantation EXCEPT
A. Active infection
B. Age over 65 years
C. History of medical noncompliance
D. Severe renal insufficiency
Answer A.
Explanation: Active infection is considered a potentially reversible
contraindication to cardiac transplantation. The other conditions listed are
absolute contraindications to orthotopic cardiac transplantation.
Heterotopic cardiac transplantation, in which the patient's right heart
continues to work against the pulmonary hypertension while the donor
heart supplies systemic circulation, is used for a certain number of patients
with pulmonary hypertension. (See Schwartz 7th ed.)
After completion of the vascular
anastomoses, drainage of a transplanted
pancreas is accomplished by anastomosis to
A. Right colon
B. Left colon
C. Duodenum
D. Bladder or small bowel
Answer D
Explanation: Once the pancreas is revascularized, a drainage procedure must be
performed to handle the pancreatic exocrine secretions. Options include
anastomosing the donor duodenum to the recipient bladder or to the small bowel,
with the small bowel either in continuity or connected to a Roux-en-Y limb. Some
centers always use enteric drainage, others always use bladder drainage, and
others tailor the approach according to the recipient category. Both enteric drainage
and bladder drainage now have a relatively low surgical risk. The main advantage of
bladder drainage is the ability to directly measure enzyme activity in the pancreatic
graft exocrine secretions by measuring the amount of amylase in the urine. A
decrease in urine amylase is a sensitive marker for rejection, even though it is not
entirely specific. Urine amylase always decreases before hyperglycemia ensues. A
rise in serum amylase may precede a decrease in urine amylase, but serum
amylase by itself is less sensitive (it does not always rise, but urine amylase always
decreases), and is no more specific for the diagnosis of rejection. The leak rate is
the same whether the pancreas is drained to the bladder or to the bowel, but the
consequences of a bladder leak are much less severe than those associated with a
bowel leak. The disadvantages of bladder drainage include complications such as
dehydration and acidosis (from loss of alkalotic pancreatic secretions in the urine),
and local problems with the bladder such as infection, hematuria, stones, and
urethritis. Because of these chronic complications, between 10 and 20% of bladderdrained graft recipients are ultimately converted to enteric drainage.
Enteric drainage is more physiologic and has fewer long-term complications.
Absolute contraindications for donation of a
heart include all of the following EXCEPT
A. Carbon monoxide-hemoglobin level >20%
B. Prolonged cardiac arrest
C. Prolonged high-dopamine requirement
D. Significant smoking history
Answer C.
Explanation: The use of high doses of dopamine for more than 24 h
before death is a relative contraindication to transplantation of the heart.
The other listed items are all absolute contraindications to cardiac
donation. Severe structural heart disease and human immunodeficiency
virus seropositivity are other absolute contraindications. (See Schwartz 7th
ed.)
The most common cause of renal failure in
the United States is
A. Chronic glomerulonephritis
B. Chronic pyelonephritis
C. Diabetes mellitus
D. Obstructive uropathy
Answer C.
Explanation: Because the life expectancy of patients with diabetes
mellitus has dramatically lengthened by appropriate use of insulin,
diabetes is now the leading cause of renal failure and contributes to
blindness, neuropathies, and early atherosclerosis. These problems have
led to the continued interest in the possibility of pancreatic transplantation
as a form of disease control. (See Schwartz 7th ed.)
A 53-year-old man has long-standing liver
cirrhosis secondary to hepatitis C infection.
The most appropriate screening regimen
should include
I. yearly CT scan of the abdomen
II. a liver biopsy
III. liver ultrasound
IV. AFP level
V. diagnostic laparoscopy
A. I, II B. III, V C. III, IV D. I, V E. II, III
Answer C.
Explanation: The risk factors for developing HCC are well documented
and include the presence of cirrhosis, chronic active viral hepatitis
associated with elevated AFP, age >50, male gender, family history of
HCC, and previously resected or ablated HCC. Once cirrhosis has
developed, HCC is estimated to occur at the rate of 1–4% per year. This
well-documented risk for developing HCC has led to the practice of
screening and surveillance of high-risk patients for HCC. Although there
are no randomized trials comparing surveillance with no surveillance, a
National Institute of Health Consensus Panel currently recommends the
use of ultrasonography and AFP levels for early detection of HCC in highrisk populations (Fig. 28-20).
FIG. 28-20Routine screening for HCC has been demonstrated not to be
cost-effective; however, the wide availability of color-flow or power Doppler
imaging provides a rapid noninvasive modality to serially examine the liver
in patients at risk for the development of HCC. The image depicted
illustrates an HCC lesion with a hallmark arterial feeding vessel visualized
by color-flow Doppler imaging.Serum markers other than AFP have no
proven efficacy for early detection of HCC, and ultrasound has a
reasonable sensitivity (60–78%) but is operator dependent. This
Which of the following radiologic studies is
not recommended for the diagnosis of
Caroli's disease?
A. magnetic resonance imaging (MRI)
abdomen
B. CT scan abdomen
C. abdominal US
D. HIDA scan
E. ERCP
Answer D.
Explanation: Caroli's disease is an abnormal development of the
intrahepatic bile ducts without an obstructive cause, characterized by
saccular dilatations, resembling a picture of multiple cyst-like structures of
varying size. Two types have been described: a type with bile duct
abnormalities alone and a type with bile duct abnormality combined with
periportal fibrosis, similar to congenital hepatic fibrosis. This combined type
is also known as Caroli's syndrome and has been reported more frequently
than the pure type, or Caroli's disease.
Caroli's disease is anatomically characterized for saccular dilatations of the
bile ducts more frequently seen in the left side of the liver. In 30–40% of
the cases this are confined to one segment of one side of the liver.
Bilateral abnormalities are more common in the second type: Caroli's
syndrome.
The most common complications are cholangitis, septicemia, amyloidosis,
and cholangiocarcinoma (7–10% of patients). Caroli's syndrome is
associated with renal disorders such as renal cysts and nephrospongiosis
seen in 30–40% of patients. These disorders have not been seen in
Caroli's disease.
The diagnosis is made by radiologic studies such as US, CT scan, ERCP,
Immunologic rejection is mediated by the
recipient's
A. Eosinophils
B. Lymphocytes
C. Neutrophils
D. Plasma cells
Answer B.
Explanation: Early work in the transplantation field showed that graft
rejection was mediated by the recipient's white blood cells. Refinement of
the techniques involved demonstrated that the lymphocytes played the
major role in this phenomenon. The development of antilymphocyte serum
was an early step in controlling the rejection process. (See Schwartz 7th
ed.)
In the prevention of graft rejection,
cyclosporine
A. Blocks transcription of interleukin-1 (IL-1)
and tumor necrosis factor- (TNF-)
B. Inhibits lymphocyte nucleic acid
metabolism
C. Results in rapid decrease in the number of
circulatory T lymphocytes
D. Selectively inhibits T-cell activation
Answer D.
Explanation: There are a number of different agents used to control graft
rejection, and they function in different ways. Cyclosporine, the mainstay of
immunosuppression, selectively inhibits T-cell activation. Corticosteroids
block the transcription of IL-1 and TNF-. Azathioprine inhibits lymphocyte
nucleic acid metabolism. Mycophenolate mofetil inhibits RNA and DNA
synthesis. OKT3 results in a rapid decrease in circulatory T lymphocytes.
(See Schwartz 7th ed.)
Required laboratory tests in evaluation of a
patient under consideration for heart
transplantation include all of the following
EXCEPT
A. Blood type
B. Cardiac catheterization
C. Complete blood count
D. Prothrombin time and activated partial
thromboplastin time
Answer B.
Explanation: Cardiac catheterization may be indicated in some patients to
evaluate cardiac function. The other tests are required in any patient under
consideration for cardiac transplantation. (See Schwartz 7th ed.)
All of the following conditions in a potential
donor are absolute contraindications to the
use of a kidney for transplantation EXCEPT
A. Age older than 70 years
B. Chronic renal insufficiency
C. Long-standing hypertension
D. Presence of hepatitis C
Answer D.
Explanation: Cadaveric kidneys make up 75% of all donor kidneys, and
the demand far exceeds the supply. For this reason, donor criteria have
been liberalized in recent years. Advanced age, chronic renal insufficiency,
intravenous drug abuse, and long-standing hypertension remain absolute
contraindications. Human immunodeficiency virus seropositivity and the
presence of surface antigens against hepatitis B are also absolute
contraindications. Although there is risk associated with using a kidney
from a donor with evidence of hepatitis C, this condition is not considered
an absolute contraindication to kidney use. (See Schwartz 7th ed.)
Absolute contraindications to renal
transplantation for a patient with chronic
renal failure include all of the following
EXCEPT
A. Chronic active hepatitis
B. Human immunodeficiency virus infection
C. Recent operation of cancer of the colon
D. Sickle cell disease
Answer D.
Explanation: Sickle cell disease is a relative contraindication to renal
transplantation because of the associated high incidence of recurrence.
The other listed conditions are considered absolute contraindications
because of the patient's generally poor health prognosis. (See Schwartz
7th ed.)
The single most important factor in
determining whether to perform a transplant
between a specific donor and recipient is
A. Mixed lymphocyte culture assays of the
donor and recipient B. HLA types of the
donor and recipient C. ABO blood types of
the donor and recipient D. Peripheral T-cell
count of the recipient
Answer C.
Explanation: Although mixed lymphocyte culture assays and HLA typing
of the donor and recipient to determine compatibility have been shown to
enhance long-term graft survival, immediate graft function has been
correlated to the absence of the presensitized state. This presensitization
can be with respect to lymphocytotoxic antibodies or preformed
isoagglutinins. ABO compatibility is essential in renal and cardiac
transplantation because incompatibility leads to prompt destruction of the
transplanted organ. In liver transplantation, the presensitized state is of
less importance, but diminished graft survival has been demonstrated in
ABO-incompatible combinations. (See Schwartz 7th ed.)
A 24-year-old woman is admitted to the intensive care unit for sudden collapse
with progressive neurologic deficits. A computed tomography scan reveals an
intracranial tumor with evidence of acute hemorrhage. Emergent craniotomy is
done for decompression, and tissue obtained reveals high-grade malignant
astrocytoma. On postoperative day 1, the patient is placed on large doses of
phenobarbital for seizure activity but continues to deteriorate. On day 3, she
requires dopamine support at 10 mg/kg/min to maintain a systolic blood
pressure of 90 mm Hg. She develops diabetes insipidus, and her urine output is
adequate, although her creatinine rises to 1.5 mg/dL and the blood urea nitrogen
(BUN) is 40 mg/dL. A urine culture from a Foley specimen yields Escherichia coli
at 100,000/mL. On day 4, she becomes unresponsive, without evidence of
cortical or brainstem function. An electroencephalogram (EEG) is isoelectric.
Which of the following is an absolute contraindication for consideration of this
woman as a potential organ donor?
A. Presence of high-grade intracranial malignancy B. Requirement of pressor
support C. Elevated BUN and creatinine D. Presence of supratherapeutic
phenobarbital levels
Answer D.
Explanation: The presence of phenobarbital, narcotics or alcohol, or of
hypothermia is a contraindication to organ donation, even with an
isoelectric EEG. This is because these factors may suppress spontaneous
electric activity of the brain. Intracranial tumors are not considered a
contraindication, mainly because of their lack of systemic metastasis.
Other malignancies do contraindicate donation. The need for pressor is not
necessarily a contraindication, especially if these drugs are used in the
terminal period to maintain blood pressure and urine output. Elevations of
BUN and creatinine are not uncommon, especially in the face of diabetes
insipidus with prerenal azotemia. Adequate urine output is the most
important factor in consideration of renal organ donation. Lower urinary
tract infection caused by instrumentation is not a contraindication to
donation of kidneys, whereas systemic or peritoneal sepsis is. (See
Schwartz 7th ed.)
All of the following are side effects of
cyclosporine A administration for prevention
of organ rejection EXCEPT
A. Hepatotoxicity B. Hirsutism C. Tremor
D. Bone marrow depression
Answer D.
Explanation: Bone marrow depression has often been seen with
azathioprine but is not seen in patients on cyclosporine. Hepatotoxicity,
hirsutism, tremor, and nephrotoxicity are complications of prolonged use of
cyclosporine A. Nephrotoxicity is the most clinically important and most
frequently seen side effect and may limit the drug's use in some patients.
(See Schwartz 7th ed.)
Currently, which of the following infectious
illnesses is most likely to compromise
patients after renal transplantation?
A. Coli sepsis B. Pneumococcal sepsis
C. Candidiasis D. Cytomegalovirus sepsis
Answer D.
Explanation: Immunosuppression for transplantation increases the risk for
all types of infection. Use of cyclosporine, along with broad-spectrum
antibiotics, has reduced the incidence of bacterial infections. Most serious
posttransplant infections arise when rejection is being treated, and in the
past, these led to high mortality. Both Candida and Aspergillus infections
can occur but are relatively rare compared with viral infection.
Cytomegalovirus (CMV) can produce a spectrum of illness characterized
by fever, neutropenia, arthralgias, malaise, gastrointestinal ulcerations, and
decreased renal function. CMV itself produces a state of
immunosuppression, and many serious infections are superinfections in
patients already experiencing CMV infections. Treatment of CMV sepsis
includes decreasing immunosuppression and administering ganciclovir, a
new antiviral drug. (See Schwartz 7th ed.)
Postoperative indicators of primary
nonfunction of a liver allograft include all of
the following EXCEPT
A. Hypokalemia
B. Hypoglycemia
C. Elevated prothrombin time
D. Alkalosis
Answer A.
Explanation: Primary graft failure is a very serious complication. The
patient decompensates quickly, and urgent transplantation is indicated.
Severe central nervous system changes, with acid-base changes (early
alkalosis due to inability to metabolize citrate and acidosis as a terminal
event), hyperkalemia, coagulopathy, hypoglycemia, and oliguria are often
terminal events of this acute hepatic decompensation. (See Schwartz 7th
ed.)
An absolute contraindication to cardiac transplantation is
(A) Active peptic ulcer disease
(B) Age older than 60 years
(C) Fixed pulmonary vascular resistance
(D) Heavy cigarette smoking
Answer C.
Explanation: Although the other three items are relative contraindications
to cardiac transplantation, fixed pulmonary vascular resistance is the only
absolute contraindication among those listed. A heart accustomed to low
pulmonary artery pressure and resistance will fail immediately if placed in a
recipient with fixed pulmonary vascular resistance. (See Schwartz 7th ed.)
A 45-year-old female underwent a kidney
transplant 6 months ago and has been taking
cyclosporine and steroids. She developed
cholelithiasis and requires a laparoscopic
cholecystectomy. She wants to know if her
chance to have a wound infection is
increased. The best answer to her question is
A. No, steroids and cyclosporine do not
increase the chance to have wound infection
when used chronically B. Yes, because of
inhibition of collagen synthesis and fibroblast
proliferation C. Yes, because of persistent
Answer B.
Explanation: During the past two decades the survival rate of solid organ
recipients has improved dramatically. The major factor in improved clinical
outcome is the decline in death secondary to infection. Currently, 1-year
mortality caused by infection has decreased to less than 5% for renal
transplant patients. Better immunosuppression and understanding by the
clinician of drug pharmacodynamics and pharmacokinetics are responsible
for decrease morbidity and mortality after solid organ transplantation.
Steroids reduce the inflammatory process blocking transcription of cytokine
genes (especially IL-1) leading to nonspecific inhibition of T lymphocytes
and macrophages. It is well documented that steroids decrease fibroblast
migration and collagen synthesis. Topical steroids also inhibit wound
healing.
Cyclosporine is a potent immunosuppressant used to suppress transplant
rejection. Experimental evidence suggests that the effectiveness of cyclosporine is because of specific and reversible inhibition of
immunocompetent lymphocytes in the G0- or G1-phase of the cell cycle. T
lymphocytes are preferentially inhibited. The T-helper cell is the main
target, although the T-suppressor cell may also be suppressed.
Cyclosporine also inhibits lymphokine production and release of IL-2.
The best method of monitoring the
development of acute rejection in a patient
after cardiac transplantation is
A. Dipyridamole thallium study
B. Electrocardiogram C. Endomyocardial
biopsy D. Ultrasound examination of the
heart
Answer C.
Explanation: It would be desirable to follow possible rejection by some
noninvasive procedure, but none has given timely results. Endomyocardial
biopsies allow rejection to be diagnosed before significant organ damage
and dysfunction occur. (See Schwartz 7th ed.)
You are caring for a 50-year-old man who is 3
years out from a cadaveric renal transplant
for diabetic nephropathy. He had a single
episode of vascular rejection 1 month after
transplant, but otherwise has done well with
a baseline serum Cr of 1.8 mg/dL. He is
admitted to your service with increasing
fatigue, dyspnea with exertion, and acute
renal failure. His medications include
cyclosporine, mycophenolate mofetil,
prednisone, and nifedipine. On examination,
he is pale and weak with a BP of 150/95
Answer E.
Explanation: The patient has a hemolytic anemia (elevated LDH and
bilirubin), thrombocytopenia, and renal failure. Therefore, the patient meets
the criteria of HUS. The most important next step would be to obtain a
peripheral smear to document the presence of schiztocytes. HUS is
usually seen in children with bloody diarrhea associated with infection with
verotoxin producing E. coli from undercooked meat; however, HUS is also
seen in a variety of conditions including malignancy, scleroderma renal
crises, bone marrow transplantation, and the administration of the
immunosuppressants cyclosporine A and tacrolimus. In renal
transplantation, cyclosporine associated HUS may develop in up to 10% of
patients. Treatment is removal of the offending agent. Small case series
suggest that plasma exchange may be helpful.
Bibliography
Zarifian A, Meleg-Smith S, O'Donovan R, et al. Cyclosporine-associated
thrombotic microangiopathy in renal allografts. Kidney Int 1999;55:2457–
2466. [PubMed: 10354295]
All of the following examination findings are
consistent with a diagnosis of brain death
except:
A. dilated and nonreactive pupils B. absent
oculocephalic reflex C. extensor (decerebrate)
posturing D. absent gag reflex
Answer C.
Explanation: There are two reasons to declare that a patient is brain
dead. The first is to allow for organ donation, and the second is to allow for
removal of life support mechanisms once it is deemed that further medical
treatment is futile. Most state governments and hospitals refer to the
guidelines established by the President's Commission for the
determination of brain death. For older children and adults, the physical
examination must show absence of cerebral and brain stem function, no
response to deep central pain, and absence of complicating conditions
such as hypothermia or hypotension. Findings consistent with absence of
brain stem function are dilated and nonreactive pupils, absent corneal
reflexes, absent oculocephalic (doll's eyes) reflex, absent oculovestibular
reflex, and absent oropharyngeal (gag) reflex. In addition to these, the
apnea test is used to assess the function of the medulla. Brain death is
confirmed if the patient has no spontaneous respirations after allowing the
PaCO2 to reach greater than 60 (hypercapnia of this degree will always
produce spontaneous respirations in a patient with a functioning brain
stem). If a patient has extensor (decerebrate) or flexor (decorticate)
posturing in response to deep central pain, then information from the brain
stem is still being transmitted down through the spinal cord which is
Characteristics of fulminant hepatic failure
are as follows:
I. It is rarely a medical emergency.
II. It is a clinical syndrome representing a final
common pathway for a wide variety of
diseases.
III. It is most commonly because of alcohol
abuse.
IV. It has pathognomonic features making the
diagnosis evident.
V. Sometimes may not have an identifiable
cause.
Answer E.
Explanation: Acute fulminant hepatic failure is an uncommon
manifestation of liver disease that constitutes a medical emergency. It is
because of loss of hepatic parenchyma secondary to a given insult and
carries a grave prognosis (Fig. 28-9).
A 33-year-old man tested positive for
antibody to HCV when donating blood. His
liver enzymes are within normal range. The
patient is otherwise healthy, feels well, and
denies any risk factors for HCV. His physical
examination is unremarkable and shows no
stigmata of chronic liver disease. Qualitative
polymerase chain reaction (PCR) testing is
positive for HCV RNA. Which of the following
actions is most appropriate for this patient?
A. reassure the patient that he does not have
chronic HCV infection and requires no further
Answer D.
Explanation: Screening recommendations for HCV are currently practiced
according to the Centers for Disease Control recommendations. The main
transmission mode is following initiation of injection drug use, whereas the
risk of sexual transmission is low. The accuracy of anti-HCV testing
(enzyme immunoassay) depends on the pretest probability of disease. The
predictive value in a patient with known parenteral exposure exceeds 90%,
whereas the predictive value of a positive anti-HCV test in blood donors
with a normal alanine aminotransferase (ALT) level and no risk factor for
HCV infection is less than 50%. In this situation, direct measurement of
HCV RNA by PCR assay is required.
Seventy to 85% of patients initially infected with HCV develop persistent
infection. In approximately 15% of patients, HCV infection resolves within
1–6 months, possibly because of HCV-specific T-cell function. Of those
patients with persistent infection, 20% have chronic viremia with normal
liver enzymes. In this group of patients, risk of progression to cirrhosis is
low. On the other hand, patients with a consistently or intermittently
elevated ALT level have a 20% risk of developing cirrhosis over 20 years.
The risk of hepatic decompensation manifesting as ascites, variceal bleed,
encephalopathy, or loss of hepatic synthetic ability averages about 3–5%
Which of the following dietary changes will
improve the Child-Pugh classification in endstage liver patients with protein-calorie
malnutrition?
A. lactoalbumin supplementation B. oral
intake of fat soluble vitamin K C. maltodextrin
supplementation D. branched chain amino
acid supplementation E. long-term parenteral
nutrition
Answer D.
Explanation: Malnutrition in the end-stage liver failure patient plays a
significant role in outcome. The nutritional deficiencies are mainly because
of protein malnutrition and have been shown to be an independent risk
factor for mortality and life-threatening complication. The factors causing
the protein loss and failure of intake are the hypermetabolism associated
with end-stage liver failure necessitating a greater protein intake. A protein
load in these patients can, in turn, lead to worsening encephalopathic
changes.
Branched chain amino acid supplements have been used successfully in
cirrhotic patients to increase the protein intake to combat nitrogen losses,
while avoiding encephalopathic changes.
Long-term studies assessing the benefits of oral branched chain amino
acid supplementation in these patients have found that there is no
statistically significant difference in mortality. When compared with
equivalent caloric and protein oral supplementation there have been
shown to be significant improvements in Child-Pugh score, number of
required hospital admissions, bilirubin, anorexia, and health-related quality
of life. Nutritional support with branched chain amino acids has improved
anthropometric measurements in this subset of malnourished patients and
A 25-year-old female is brought to the local
emergency room with signs and symptoms
compatible with encephalopathy. Her family
members report that she had been jaundiced
over the past few days and had recently
separated with her boyfriend. She had been
otherwise healthy and on no medications.
The most likely etiology and best treatment
course include the following.
I. Hepatic failure in this setting is usually
secondary to viral hepatitis.
II. The patient should receive broad-spectrum
Answer E.
Explanation: The time course of fulminant hepatic failure has an etiologic
and prognostic significance. An illness of 1 week or less before the
development of failure is usually suggestive of hepatic ischemia or
acetaminophen toxicity. On the other hand, illness longer than 4 weeks is
more likely the result of viral hepatitis or hepatic failure of unknown
etiology.
Patients who are ill for more than 8 weeks before they develop
encephalopathy have a higher chance of developing portal hypertension,
whereas patients with illness of shorter duration (<4 weeks) are more likely
to develop cerebral edema. Encephalopathy preceded by 1 week of
jaundice is a poor prognostic indicator.
Because of its easy availability, acetaminophen is a commonly used drug
for suicide. This is also a problem with other over-the-counter remedies
that contain acetaminophen as an active ingredient.
Although infectious complication may develop in up to 80% of patients with
fulminant hepatic failure, prophylactic antibiotic therapy is still
controversial. A wide variety of therapies have been proposed and used for
the treatment of this disease, including corticosteroids, prostaglandins, and
exchange transfusion, yet none have proved efficacious. Only the
A 26-year-old surgery resident is evaluated
for malaise, fatigue, myalgia, and low-grade
fever. He was previously well and denies illicit
drug use, transfusions, or recent travel. He
admits though to multiple needle stick
accidents. Physical examination reveals
jaundice and hepatomegaly. Laboratory
studies are as follows: AST 1000 U/L, ALT
2000 U/L, INR 1.0, total bilirubin 4 mg/dL, IgG
anti-HAV positive, IgM anti-HAV negative,
HBsAg positive, IgG anti-HBc positive, IgM
anti-HBc positive, anti-HCV negative.
Answer B.
Explanation: HBV is primarily transmitted by parenteral and mucous
membrane exposure to infectious body fluids such as blood, serum,
semen, and saliva. Risk factors include close personal or intimate
exposure to an infected household contact or sexual partner, intravenous
drug use, tattooing and body piercing, unapparent blood inoculations as
with shared razor blades, blood transfusion or exposure to blood products,
hemophilia and hemodialysis, and work in the health care profession.
Because of improved screening of blood donors, and educational efforts to
combat human immunodeficiency virus (HIV), the incidence of HBV
infection has declined in the United States since 1991.
Diagnosis of acute hepatitis depends on the results of specific antiviral
serology. Hospitalization is warranted for intractable symptoms of anorexia,
vomiting, or severe impairment of liver function. Other symptoms include
jaundice, weight loss, and malaise. Severe hepatic dysfunction manifests
as renal failure, metabolic acidosis, encephalopathy, variceal bleeding or
ascites.
In adults, more than 90% of HBV infection results in self-limited acute
hepatitis with subsequent resolution of the disease in 3–6 months.
Approximately 5% of patients will develop chronic hepatitis, and 1–2% will
About Caroli's disease, mark the correct
answer(s).
A. It is characterized by intrahepatic bile duct
atresia. B. Abdominal mass and weight loss
are the most common initial symptoms. C. It
is a developmental anomaly of the ductal
plate characterized by saccular dilatations of
the large bile ducts. D. It is more commonly
seen in adult females. E. It is a risk factor for
the development of cystadenocarcinoma of
the bile duct.
Answer C.
Explanation: Caroli's disease is an abnormal development of the
intrahepatic bile ducts without an obstructive cause, characterized by
saccular dilatations, resembling a picture of multiple cyst-like structures of
varying size. Two types have been described: a type with bile duct
abnormalities alone and a type with bile duct abnormality combined with
periportal fibrosis, similar to congenital hepatic fibrosis. This combined type
is also known as Caroli's syndrome and has been reported more frequently
than the pure type, or Caroli's disease.
Caroli's disease is anatomically characterized for saccular dilatations of the
bile ducts more frequently seen in the left side of the liver. In 30–40% of
the cases this are confined to one segment of one side of the liver.
Bilateral abnormalities are more common in the second type: Caroli's
syndrome.
The most common complications are cholangitis, septicemia, amyloidosis,
and cholangiocarcinoma (7–10% of patients). Caroli's syndrome is
associated with renal disorders such as renal cysts and nephrospongiosis
seen in 30–40% of patients. These disorders have not been seen in
Caroli's disease.
The diagnosis is made by radiologic studies such as US, CT scan, ERCP,
Which of the following is not a complication
of Caroli's disease?
A. stone formation B. recurrent cholangitis
C. septicemia D. cholangiocarcinoma
E. amyloidosis F. renal disorders
Answer F.
Explanation: Caroli's disease is an abnormal development of the intrahepatic bile
ducts without an obstructive cause, characterized by saccular dilatations,
resembling a picture of multiple cyst-like structures of varying size. Two types have
been described: a type with bile duct abnormalities alone and a type with bile duct
abnormality combined with periportal fibrosis, similar to congenital hepatic fibrosis.
This combined type is also known as Caroli's syndrome and has been reported
more frequently than the pure type, or Caroli's disease.
Caroli's disease is anatomically characterized for saccular dilatations of the bile
ducts more frequently seen in the left side of the liver. In 30–40% of the cases this
are confined to one segment of one side of the liver. Bilateral abnormalities are
more common in the second type: Caroli's syndrome.
The most common complications are cholangitis, septicemia, amyloidosis, and
cholangiocarcinoma (7–10% of patients). Caroli's syndrome is associated with renal
disorders such as renal cysts and nephrospongiosis seen in 30–40% of patients.
These disorders have not been seen in Caroli's disease.
The diagnosis is made by radiologic studies such as US, CT scan, ERCP, MRI
where saccular or cystically dilated intrahepatic ducts are seen. Surgical treatment
is indicated in order to reduce the risk of recurrent cholangitis, biliary cirrhosis, or
cholangiocarcinoma. Hepatic lobectomy is indicated for localized bile duct
abnormalities (Caroli's disease), while liver transplant should be considered in
selected patients with generalized disease or concomitant liver fibrosis and portal
hypertension (Caroli's syndrome).
Which of the following (Fig. 29-3) is not
considered a risk factor for
cholangiocarcinoma development?
FIG. 29-3A. primary sclerosing cholangitis
B. Caroli's disease C. choledocal cyst D. biliary
atresia E. hepatolithiasis
Answer D.
Explanation: Cholangiocarcinoma is an uncommon cancer found in 0.01–
0.2% of all autopsies. The majority of the patients are older than 65-yearold with a male predominance.
The etiology is unknown, but several predisposing conditions have been
identified:
1. Primary sclerosing cholangitis have a 6–30% chance of developing it
and 10–30% of patients who undergo liver transplant for PSC have an
occult cholangiocarcinoma. (See Fig. 29-3.)
2. Congenital biliary cystic disease (Caroli's disease, choledochal cyst)
have a 15–20% chance of cancer.
3. Hepatolithiasis (recurrent pyogenic cholangitiohepatitis or oriental
cholangiohepatitis), prevalent in Japan, secondary to chronic portal
bacteremia and portal phlebitis which may give rise to intrahepatic pigment
stone formation.
4. Biliary parasites, especially Clonorchis sinensis and Opisthorchis
viverrini, are associated with an increased risk.
5. Carcinogens such as thorium, radon, nitrosamines, dioxin, and
asbestos.
Different classifications have been used to describe this tumor.
A patient is brought to the ER 3 months
following liver transplantation. The patient
had been doing well until about 1 week prior
to admission when he because confused,
tremulous and complained of unsteadiness
and difficulty with vision. An MR scan showed
T2 hyperintense lesions in both occipital
lobes (Fig. 35-18). The most likely diagnosis is
FIG. 35-18
Axial T2-weighted MRI of the brain, revealing
white matter hyperintensity in both occipital
lobes.
Answer B.
Explanation: Cyclosporin toxicity can result in the posterior
leukoencephalopathy syndrome. There are a variety of acute illnesses that
can result in a reversible encephalopathy secondary to edema of the
cerebral white matter, most prominently in the occipital and posterior
parietal and temporal regions of the brain. Clinically the syndrome is
manifested by the subacute onset of headache, lethargy, confusion,
altered mental status, seizures, and difficultly with vision. The white matter
edema is visible as decreased attenuation on CT scans and hypointensity
on T1 and hyperintensity on T2 MR scans. Originally described in
encephalopathy associated with malignant hypertension and eclampsia of
pregnancy, the syndrome also occurs secondary to toxicity of cyclosporin
and other immunosuppressants. White matter edema results from
disruption of the blood-brain barrier. The mechanism for this disturbance is
not entirely clear in cases of immunosuppression. The syndrome can occur
with levels of drug in the therapeutic range and is probably the result of a
vasculopathy caused by the medication. The syndrome is reversible by
discontinuing or lowering the drug level. The radiologic abnormalities often
resolve completely within several weeks.
Creutzfeldt-Jakob's disease is a prion (proteinaceous infectious particle)