TABLE IV-114 Risk Factors for Active Tuberculosis Among Persons Who Have Been Infected With Tubercle Bacilli 23 page

Following the initial period, a taper should be achieved over a period of 4 weeks. Alternatively, pentoxifylline 400 mg three times daily for 4 weeks can also be used.

УШ-54. The answer is C.(Chap. 308) The clinical presentation is consistent with a cholestatic picture, which can present with painless jaundice and pruritus. The pruritus can be prominent and is present in 50% of individuals at the time of diagnosis. The pruritus is typically intermittent and worse in the evening. There is no other prominent association such as following hot baths or showers, which occurs in polycythemia vera. Other causes of pruritus outside of cholestasis include lymphoma and uncontrolled hypo-or hyperthyroidism. However, the laboratory studies in this patient clearly represent cholestasis with an elevation in alkaline phosphatase and bilirubin. The clinical characteristics are more commonly seen in primary biliary cirrhosis compared to primary sclerosis cholangitis, as the patient is a middle-aged female with positive antimitochondrial antibodies. In contrast, primary sclerosing cholangitis is associated with positive perinuclear antineutrophil cytoplasmic antibodies in 65% of patients, and 50% of individuals with primary sclerosing cholangitis have a history of ulcerative colitis.

УШ-55. The answer is B.(Chap. 308) Esophageal varices develop in the setting of portal hypertension associated most commonly with cirrhotic liver disease. In recent years, patients with cirrhosis have been commonly screened for varices by endoscopy, as about 33% will have varices on examination. Moreover, it is estimated that one-third of individuals with varices will develop bleeding. As this patient does not have medical care, it is unknown whether he has varices, but with the large volume of bleeding the patient has experienced, the treating physician should assume that the patient has variceal bleeding and act accordingly. The first step in the treatment of any individual with acute gastrointestinal bleeding is to ensure appropriate large-bore IV access, preferably in a large central vein or the antecubital fossae, and begin volume resuscitation. Volume resuscitation should be initiated with normal saline, and blood products should be administered when available. Once volume resuscitation has been initiated, emergent consultation with GI for endoscopic evaluation should be obtained. Endoscopic treatment should include esophageal band ligation, but in the acute setting, sclerotherapy may be used to control local bleeding with band ligation occurring at a future point in time. If emergent endoscopy is not an option, placement of a Sengstaken-Blakemore or Minnesota tube to tamponade bleeding should be employed. In addition, vasoconstricting agents are used to decrease splanchnic blood flow. While vasopressin was initially the agent of choice, cardiovascular ischemia can occur with the high doses used in GI bleeding. The currently preferred agents are octreotide or somatostatin by continuous infusion. Nonspecific beta blockers such as propranolol or nadolol are used for the primary or secondary prevention of variceal bleeding, but are not prescribed in the acute setting as these agents could worsen hypotension.

УШ-56. The answer is A.(Chap. 308) The cornerstone of the management of ascites is sodium restriction to less than 2 g daily. A common misconception is to institute a fluid restriction as well. However, this is neither effective nor necessary. With a sodium restriction to 2 g daily, most mild ascites can be managed quite well. If sodium restriction alone fails to correct ascites, then initiation of diuretics is required. Spironolactone at a dose of 100-200 mg daily is the initial diuretic used for ascites and can be titrated as high as 400-600 mg daily if tolerated. Loop diuretics can be added to spironolactone. The typical agent is furosemide beginning at 40-80 mg daily with the maximum doses being about 120-160 mg daily. Care must be taken to avoid renal dysfunction with loop diuretics, and

higher doses may not be tolerated. If ascites is refractory to these treatments, transjugular intrahepatic portosystemic shunts (TIPS) can be considered. This procedure creates a portocaval shunt be introducing an expandable metal stent from the hepatic veins through the substance of the liver into the portal veins, creating a direct portocaval shunt. Thus, TIPS decreases portal pressures to decrease ascites and the risk of variceal bleeding. However, hepatic encephalopathy typically worsens following TIPS.

УШ-57. The answer is A.(Chap. 308) Severe right-sided heart failure may lead to chronic liver injury and cardiac cirrhosis. Elevated venous pressure leads to congestion of the hepatic sinusoids and of the central vein and centrilobular hepatocytes. Centrilobular fibrosis develops, and fibrosis extends outward from the central vein, not the portal triads. Gross examination of the liver shows a pattern of "nutmeg liver." Although transaminases are typically mildly elevated, severe congestion, particularly associated with hypotension, may result in dramatic elevation of AST and ALT 50- to 100-fold above normal. Budd-Chiari syndrome, or occlusion of the hepatic veins or inferior vena cava, may be confused with congestive hepatopathy. However, the signs and symptoms of congestive heart failure are absent in patients with Budd-Chiari syndrome, and these patients can be easily distinguished clinically from those with heart failure. Venoocclusive disease may result from hepatic irradiation and high-dose chemotherapy in preparation for hematopoietic stem cell transplantation. It is not a typical complication of liver transplantation. Although echocardiography is a useful tool for assessing left and right ventricular function, findings may be unimpressive in patients with constrictive pericarditis. A high index of suspicion for constrictive pericarditis (e.g., prior episodes of pericarditis, mediastinal irradiation) should lead to a right-sided heart catheterization with demonstration of "square root sign," which is the limitation of right heart filling pressure in diastole that is suggestive of restrictive cardiomyopathy. Cardiac magnetic resonance imaging may also be helpful in determining which patients should proceed to cardiac surgery.

УШ-58. The answer is B.(Chap. 308) The presence of cirrhosis in an elderly woman with no prior risk factors for viral or alcoholic cirrhosis should raise the possibility of primary biliary cirrhosis (PBC). It is characterized by chronic inflammation and fibrous obliteration of intrahepatic ductules. The cause is unknown, but autoimmunity is assumed, as there is an association with other autoimmune disorders, such as autoimmune thyroiditis, CREST syndrome, and the sicca syndrome. The vast majority of patients with symptomatic disease are women. The antimitochondrial antibody test (AMA) is positive in over 90% of patients with PBC and only rarely is positive in other conditions. This makes it the most useful initial test in the diagnosis of PBC. Since there are false positives, if AMA is positive a liver biopsy is performed to confirm the diagnosis. The 24-hour urine copper collection is useful in the diagnosis of Wilson's disease. Hepatic failure from Wilson's disease typically occurs before age 50. Hemochromatosis may result in cirrhosis. It is associated with lethargy, fatigue, loss of libido, discoloration of the skin, arthralgias, diabetes, and cardiomyopathy. Ferritin levels are usually increased, and the most suggestive laboratory abnormality is an elevated transferrin saturation percentage. Although hemochromatosis is a possible diagnosis in this case, PBC is more likely in light of the clinical scenario. Although chronic hepatitis В and hepatitis С are certainly in the differential diagnosis and must be ruled out, they are unlikely because of the patient's history and lack of risk factors.

УШ-59. The answer is D.(Chap. 309) This patient presents with nonalcoholic fatty liver disease

(NAFLD) that has progressed to cirrhosis. It is now commonly thought that many individuals previously identified as having cryptogenic cirrhosis had NAFLD as a cause of end-stage liver disease. With the rising prevalence of obesity in the United States and Europe, NAFLD is expected to continue to rise. At present, the prevalence of NAFLD is estimated between to be 14-20%. Of these individuals, 30-40% with nonalcoholic steato-hepatitis will develop advanced fibrosis and 10-15% will develop outright cirrhosis. Most patients diagnosed with NAFLD are asymptomatic with incident note of elevated liver enzymes found on testing for other reasons. The ALT is typically slightly higher than the AST, and both enzymes are only mildly elevated. In most instances the ALT and AST are only 1.5-2 times the upper limit of normal. NAFLD often accompanies other components of the metabolic syndrome, with insulin resistance being a common link between these disorders. The diagnosis of NAFLD requires a careful history and examination to rule out other disorders. Alcohol intake should be less than 20 g/d. Comprehensive testing should include serologies for viral hepatitis, iron studies, ceruloplasmin, 04

antitrypsin levels, and autoimmune serologies. Liver biopsy most commonly shows macrovesicular steatosis with a mixed inflammatory infiltrate in a lobular distribution. The fibrosis that occurs has a characteristic perivenular and perisinusoidal distribution. In cirrhotic patients, steatosis may not be seen, but can recur following transplant. The only known effective treatment for NAFLD is weight loss and exercise. Thiazolidinediones are currently being studied given their effects on insulin resistance. In addition, ongoing research into statins and ursodeoxycholic acid is being undertaken, but no specific medication can be recommended at this point for patients with NAFLD.

УШ-60. The answer is C.(Chap. 310) In the United States, over 6000 individuals undergo liver transplants yearly. However, the demand for organs far outpaces the supply with a waiting list of over 16,000 individuals. The most common reasons for liver transplant are alcoholic cirrhosis and chronic hepatitis С infection. When evaluating someone for liver transplantation, it is important to ensure that the patient is an appropriate candidate. For individuals with alcoholic cirrhosis, sustained abstinence and recovery need to be demonstrated, although the recidivism rate is as high as 25% after transplantation. Absolute contraindications to liver transplant include uncontrolled infection, active substance or alcohol abuse, extrahepatobiliary malignancy (excluding nonmelanoma skin cancer), metastatic malignancy to the liver, AIDS, or life-threatening or advance systemic disease. Cholangiocarcinoma almost invariably recurs following liver transplantation. Thus, it is now considered a contraindication to transplant. While primarily performed in children, living donor transplantation is increasingly being considered in adults given the poor availability of cadaveric organs. In living donor transplantation, typically the right lobe of the liver is taken from a suitable healthy donor. Currently, living donor transplantation accounts for 4% of all liver transplants. It is certainly not without risk. The average healthy donor will be medically disabled for at least 10 weeks, and the risk of death for the donor is 0.2-0.4%. Individuals receiving all forms of liver transplant have demonstrated increasing survival over the past decades. The current 5-year survival rate is more than 60%. Following transplantation, however, rejection, infection, and recurrence of primary disease can occur. For chronic hepatitis В infection, reinfection of the transplant frequently occurs, but this may be reduced to as little as 35% with post-transplantation treatment with hepatitis В immunoglobulin. For hepatitis C, reinfection is universal and is associated with the development of allograft cirrhosis in 20-30% of patients within 5 years. Autoimmune diseases can also recur in the transplanted liver, although it can be difficult to differentiate between the autoimmune disease and rejection. Wilson's disease and 04 antitrypsin deficiency, however, do not recur following transplantation.

УШ-61. The answer is E.(Chap. 310) The patient has advanced cirrhosis with a high risk of mortality, as evidenced by his episode of spontaneous bacterial peritonitis. His diabetes and remote skin cancer (since it was a basal cell carcinoma, not melanoma) are not absolute contraindications for liver transplantation, but active alcohol abuse is. The other absolute contraindications to transplantation are life-threatening systemic disease, uncontrolled infections, preexisting advanced cardiac or pulmonary disease, metastatic malignancy, and life-threatening congenital malignancies. Ongoing drug or alcohol abuse is an absolute contraindication, and patients who would otherwise be suitable candidates should immediately be referred to appropriate counseling centers to achieve abstinence. Once that is achieved for an acceptable period of time, transplantation can be considered. Indeed, alcoholic cirrhosis accounts for a substantial proportion of the patients who undergo liver transplantation.

УШ-62. The answer is B.(Chap. 311) In the National Health and Nutrition Examination Survey, the prevalence of gallstone disease in the United States was 7.9% in men and 16.6% in women. While the disease is quite prevalent, not all patients with gallstone disease require cholecystectomy. It is estimated that 1-2% of patients with asymptomatic gallstone disease will develop complications that will require surgery yearly. Therefore, it is important to know which patients with asymptomatic gallstones require referral for surgery. The first factor to consider is whether the patient has symptoms that are caused by gallstones and whether they are frequent enough and severe enough to necessitate surgery. Commonly called biliary colic, the classic symptoms of gallstone disease are right upper quadrant pain and fullness that begins suddenly and can last as long as 5 hours. Nausea and vomiting can accompany the episode. Vague symptoms of epigastric fullness, dyspepsia, and bloating following meals should not be considered biliary colic. A second factor that would be considered in recommending a patient for cholecystectomy is whether the patient has a prior history of complications of gallstone disease such as pancreatitis or acute cholecystitis. A final factor that would lead to the recommendation for cholecystectomy is the presence of anatomical factors that would increase the likelihood of complications such as a porcelain gallbladder or congenital abnormalities of the biliary tract. Individuals with very large stones (>3 cm) would also need to be considered carefully for cholecystectomy. Ursodeoxycholic acid can be used in some instances to dissolve gallstones. It acts to decrease the cholesterol saturation of bile and also allows the dispersion of cholesterol from stones by producing a lamellar crystalline phase. It is only effective, however, in individuals with radiolucent stones measuring less than 10 mm.

УШ-63. The answer is D.(Chap. 311) A practitioner needs to have a high index of suspicion for acalculous cholecystitis in critically ill patients who develop decompensation during the course of treatment for the underlying disease and have no other apparent source of infection. Some predisposing conditions for the development of acalculous cholecystitis include serious trauma or burns, postpartum following prolonged labor, prolonged parenteral hyperalimentation, and the postoperative period following orthopedic and other major surgical procedures. The clinical manifestations of acalculous cholecystitis are identical to calculous disease, but the disease is more difficult to diagnose. Ultrasonography and CT scanning typically only show biliary sludge, but they may demonstrate large and tense gallbladders. Hepatobiliary scintigraphy often shows delayed or absent gallbladder emptying. Successful management relies on accurate and early diagnosis. In critically ill patients, a percutaneous cholecystostomy may be the safest immediate procedure to decompress an infected gallbladder. Once the patient is stabilized, early elective cholecystectomy should be considered. Metronidazole to provide anaerobic coverage should be added, but this would not elucidate or adequately treat the

underlying condition.

УШ-64. The answer is C.(Chap. 311) 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.

УШ-65. The answer is B.(Chaps. 42 and 311) The clinical presentation is consistent with a cholestatic picture. Painless jaundice always requires an extensive workup, as many of the underlying pathologies are ominous and early detection and intervention often offers the only hope for a good outcome. The gallbladder showed no evidence of stones and the patient shows no evidence of clinical cholecystitis, and so a hepatobiliary iminodiacetic acid (HIDA) scan is not indicated. Similarly, antibiotics are not necessary at this point. The cholestatic picture without significant elevation of the transaminases on the liver function tests makes acute hepatitis unlikely. Antimitochondrial antibodies are elevated in cases of primary biliary cirrhosis (PBC), which may present in a similar fashion. However, PBC is far more common in women than in men, and the average age of onset is the fifth or sixth decade. The lack of an obvious lesion on CT scan does not rule out a source of the cholestasis in the biliary tree. Malignant causes such as cholangiocarcinoma and tumor of the ampulla of Vater, and nonmalignant causes such as sclerosing cholangitis and Caroli's disease may be detected only by direct visualization with endoscopic retrograde cholangiopancreatography (ERCP). ERCP is useful both diagnostically and therapeutically, as stenting procedures may be done to alleviate the obstruction.

УШ-66. The answer is A.{Chap. 313) The most common cause of acute pancreatitis in the United States is gallstones causing common bile duct obstruction. Although bile duct obstruction may be demonstrated on technetium HIDA scan, right upper quadrant ultrasound is preferred for ease, demonstration of gallstones in the gallbladder, and demonstration of obstructed bile duct. Alcohol is the second most common cause, followed by complications of endoscopic retrograde cholangiopancreatography (ERCP). Hypertriglyceridemia accounts for 1-4% of cases with triglyceride levels usually greater than 1000 mg/dL. Other potential causes of pancreatitis include trauma, postoperative states, drugs such as valproic acid, anti-HIV medications, estrogens, and sphincter of Oddi dysfunction. Additionally, there are a number of rare causes that have been described. The most judicious first step in evaluation is to test for gallstones and pursue more rare causes after the most common cause has been ruled out.

УШ-67. The answer is A.(Chap. 313) Physical examination in acute pancreatitis commonly shows an uncomfortable patient often with low-grade fever, tachycardia, and hypotension. Abdominal tenderness and muscle rigidity are often present to varying degrees. Cullen's sign is a faint blue discoloration around the umbilicus that may occur as the result of hemoperitoneum. Turner's sign is blue-red-purple or green-brown discoloration of the flanks from tissue catabolism of hemoglobin. Both of these signs indicate the presence of severe necrotizing pancreatitis.

УШ-68. The answer is E. (Chap. 313) The BISAP (Bedside Index of Severity in Acute Pancreatitis) score has recently replaced Ramon's criteria and APACHE II severity scores as the recommended modality to assess the severity of pancreatitis due to the cumbersome nature of the prior scores and the requirement of prior scores to collect large amounts of clinical and laboratory data over time. Furthermore, the APACHE II and Ramon's scoring mechanisms did not have acceptable positive and negative predictive values in predicting severe acute pancreatitis. The BISAP score incorporates five variables in determining severity: BUN greater than 35 mg/dL, impaired mental status, presence of SIRS, age above 60 years, and pleural effusion on radiography. The presence of three or more of these factors is associated with substantially increased risk for in-hospital mortality. Additional risk factors initially predicting severity include BMI of 30 or above and comorbid disease.

УШ-69. The answer is E. (Chap. 313) Several trials over the last several decades have demonstrated that there is no role for prophylactic antibiotics in the management of either interstitial or necrotizing pancreatitis. Antibiotics are recommended for only patients who appear septic at presentation while awaiting the results of culture data. If cultures are negative, antibiotics should be discontinued to decrease the risk of the development of fungal superinfection. Similarly, several drugs have been evaluated in the treatment of acute pancreatitis and found to be of no benefit. These drugs include H₂

blockers, glucagon, protease inhibitors such as aprotinin, glucocorticoids, calcitonin, nomteroidal anti-inflammatory drugs, and lexipafant, a platelet-activating factor inhibitor. A recent meta-analysis of somatostatin, octreotide, and the antiprotease gabexate mesylate in the therapy of acute pancreatitis suggested a reduced mortality rate but no change in complications with octreotide, and no effect on mortality but reduced pancreatic damage with gabexate.

УШ-70. The answer is C. (Chap. 313) Persistent inflammatory changes in the pancreas may remain for weeks to months after an episode of acute pancreatitis. Similarly, there may be prolonged elevation of amylase and lipase. In this regard, persistent changes on CT or persistent pancreatic enzyme elevation should not discourage clinicians from feeding hungry patients with acute pancreatitis. Although there had been prior concern that feeding patients with pancreatitis may exacerbate pancreatic inflammation, this has not been borne out. Similarly, enteral feeding with a nasojejunal tube in patients with acute pancreatitis has been demonstrated to have fewer infectious complications than feeding with total parenteral nutrition. Became of this, nasogastric feeding is the preferred method of nutritional support in acute pancreatitis. Enteral feeding also helps to maintain the integrity of the intestinal tract in acute pancreatitis.

УШ-71. The answer is D. (Chap. 313) The pathophysiology of acute pancreatitis evolves in three phases. During the initial phase, pancreatic injury leads to intrapancreatic activation of digestive enzymes with subsequent autodigestion and acinar cell injury. Acinar injury is primarily attributed to activation of zymogens (proenzymes), particularly trypsinogen, by lysosomal hydrolases. Once trypsinogen is converted to trypsin, the activated trypsin further perpetuates the process by activating other zymogens to further autodigestion. The inflammation initiated by intrapancreatic activation of zymogens leads to the second phase of acute pancreatitis, with local production of chemokines that cames activation and sequestration of neutrophils in the pancreas. Experimental evidence suggests that neutrophilic inflammation can also came further activation of trypsinogen, leading to a cascade of increasing acinar injury. The third phase of acute pancreatitis reflects the systemic processes that are earned by release of inflammatory cytokines and activated proenzymes into the systemic circulation.

This process can lead to the systemic inflammatory response syndrome with acute respiratory distress syndrome, extensive third-spacing of fluids, and multiorgan failure.

УШ-72. The answer is D.(Chap. 313) Chronic pancreatitis is a common disorder in any patient population with relapsing acute pancreatitis, especially patients with alcohol dependence, pancreas divisum, and cystic fibrosis. The disorder is notable for both endocrine and exocrine dysfunction of the pancreas. Often diabetes ensues as a result of loss of islet cell function; though insulin-dependent, it is generally not as prone to diabetic ketoacidosis or coma as are other forms of diabetes mellitus. As pancreatic enzymes are essential to fat digestion, their absence leads to fat malabsorption and steatorrhea. In addition, the fat-soluble vitamins, A, D, E, and K, are not absorbed. Vitamin A deficiency can lead to neuropathy. Vitamin В₁₂, or cobalamin, is often deficient. This deficiency is

hypothesized to be due to excessive binding of cobalamin by cobalamin-binding proteins other than intrinsic factor that are normally digested by pancreatic enzymes. Replacement of pancreatic enzymes orally with meals will correct the vitamin deficiencies and steatorrhea. The incidence of pancreatic adenocarcinoma is increased in patients with chronic pancreatitis, with a 20-year cumulative incidence of 4%. Chronic abdominal pain is nearly ubiquitous in this disorder, and narcotic dependence is common. Niacin is a water-soluble vitamin, and absorption is not affected by pancreatic exocrine dysfunction.

У1П-73. The answer is A.(Chap. 313) This patient likely has chronic pancreatitis related to longstanding alcohol use, which is the most common cause of chronic pancreatitis in adults in the United States. Chronic pancreatitis can develop in individuals who consume as little as 50 g of alcohol daily (equivalent to -30-40 ounces of beer). The patient's description of his loose stools is consistent with steatorrhea, and the recurrent bouts of abdominal pain are likely related to his pancreatitis. In most patients, abdominal pain is the most prominent symptom. However, up to 20% of individuals with chronic pancreatitis present with symptoms of maldigestion alone. The evaluation for chronic pancreatitis should allow one to characterize the pancreatitis as large- vs. small-duct disease. Large-duct disease is more common in men and is more likely to be associated with steatorrhea. In addition, large-duct disease is associated with the appearance of pancreatic calcifications and abnormal tests of pancreatic exocrine function. Women are more likely to have small-duct disease, with normal tests of pancreatic exocrine function and normal abdominal radiography. In small-duct disease, the progression to steatorrhea is rare, and the pain is responsive to treatment with pancreatic enzymes. The characteristic findings on CT and abdominal radiograph of this patient are characteristic of chronic pancreatitis, and no further workup should delay treatment with pancreatic enzymes. Treatment with pancreatic enzymes orally will improve maldigestion and lead to weight gain, but they are unlikely to fully resolve maldigestive symptoms. Narcotic dependence can frequently develop in individuals with chronic pancreatitis due to recurrent and severe bouts of pain. However, as this individual's pain is mild, it is not necessary to prescribe narcotics at this point in time. An ERCP or magnetic resonance cholangiopancreatography (MRCP) may be considered to evaluate for a possible stricture that is amenable to therapy. However, sphincterotomy is a procedure performed via ERCP that may be useful in treating pain related to chronic pancreatitis and is not indicated in the patient. Angiography to assess for ischemic bowel disease is not indicated as the patient's symptoms are not consistent with intestinal angina. Certainly, weight loss can occur in this setting, but the patient usually presents with complaints of abdominal pain after eating and pain that is out of proportion with the clinical examination. Prokinetic agents would likely only worsen the patient's malabsorptive symptoms and are not indicated.

SECTION IX

Rheumatology and Immunology

QUESTION

DIRECTIONS: Choose the one best response to each question.

IX-1. All of the following are key features of the innate immune system EXCEPT:

A. Exclusively a feature of vertebrate animals.

B. Important cells include macrophages and natural killer lymphocytes.

Date: 2016-04-22; view: 754