Abdomen and Pelvis

Question 1

Achalasia is characterized by the triad of: x,x and x

Causes:

Answer 1

incomplete lower esophageal sphincter relaxation, increased lower esophageal sphincter tone, and aperistalsis of the esophagus

Although there is some increased risk for esophageal cancer, it is not considered great enough to warrant surveillance endoscopy

Primary very rare
Chagas disease - most common
Other causes of achalasia-like disease include diabetic autonomic neuropathy; infiltrative disorders such as malignancy, amyloidosis, and sarcoidosis; systemic sclerosis; or lesions of dorsal motor nuclei (e.g., following polio). Lower esophageal sphincter dysfunction also occurs in association with Down syndrome or as part of Allgrove (triple-A) syndrome, an autosomal recessive disorder characterized by achalasia, alacrima, and adrenocorticotropic hormone–resistant adrenal insufficiency. The association of some achalasia cases with remote herpes simplex virus 1 (HSV1) infection, linkage of immunoregulatory gene polymorphisms to achalasia, and occasional coexistence of Sjögren syndrome or autoimmune thyroid disease suggest that achalasia may also be driven by immune-mediated destruction of inhibitory esophageal neurons

Question 2

Esophageal Causes of Hematemesis

Answer 2

Question 3

Barrett esophagus is a complication of chronic GERD that is characterized by x within the esophageal squamous mucosa and is associated with an increased risk of cancer

Answer 3

intestinal metaplasia

Question 4

H. pylori are spiral-shaped or curved bacilli present in gastric biopsy specimens of almost all patients with x ulcers as well as most individuals with gastric ulcers or chronic gastritis. Acute H. pylori infection does not produce sufficient symptoms to come to medical attention in most cases; it is the chronic gastritis that ultimately causes the individual to seek treatment. H. pylori organisms are present in the majority of individuals with chronic antral gastritis.

Answer 4

duodenal

Question 5

The x is the preferred biopsy site for evaluation of H. pylori gastritis because it is most commonly infected.

Answer 5

antrum

Question 6

Autoimmune atrophic gastritis is characterized by:
…, what cells involved

?location

Answer 6

*Autoimmune atrophic gastritis is associated with loss of parietal cells, which are responsible for secretion of gastric acid and intrinsic factor. Antibodies can be detected in serum and gastric secretions.

The absence of acid production stimulates gastrin release, resulting in hypergastrinemia and hyperplasia of antral gastrin-producing G cells. Vitamin B 12 deficiency

Autoimmune atrophic gastritis is characterized by diffuse damage to the oxyntic (acid-producing) mucosa within the body and fundus. The antrum and cardia are typically spared.

Question 7

Risk Factors for Peptic Ulcer Disease

Answer 7

Question 8

Stomach cancer

The risk of adenocarcinoma is greatest in x

Answer 8

autoimmune metaplastic atrophic gastritis.

Question 9

After H. pylori and NSAIDs, autoimmune atrophic gastritis is the most frequent cause of chronic gastritis.

x develops in all forms of chronic gastritis and is a risk factor for x.

Answer 9

Intestinal metaplasia
gastric adenocarcinoma

Question 10

Most gastric adenomas develop in a background of chronic gastritis with atrophy and intestinal metaplasia, with the exception of those associated with germline mutations in APC or MUTYH.

The risk of adenocarcinoma within gastric adenomas correlates with size and is particularly elevated in lesions greater than x cm in diameter.

Gastric adenomas have a greater risk of cancer (up to 30% when large) and must be managed more aggressively than colonic adenomas.

Answer 10

2cm

Question 11

x loss is a key step in the development of diffuse gastric cancer. CDH1 mutations are also common in sporadic and familial lobular carcinoma of the breast, which, like diffuse gastric cancer (see later), tends to infiltrate as single cells.

In contrast to diffuse gastric cancers, intestinal-type gastric cancers are strongly associated with mutations x.

Answer 11

E-cadherin
that result in increased signaling via the Wnt pathway

Question 12

Stomach cancer

Diffuse infiltrative growth pattern are typically composed of x

intestinal morphology form bulky tumors and are composed of glandular structures

Answer 12

signet-ring cells

*The depth of invasion and the extent of nodal and distant metastases remain the most powerful prognostic indicators in gastric cancer.

Question 13

A mass may be difficult to appreciate in diffuse gastric cancer, but these infiltrative tumors often evoke a desmoplastic reaction that stiffens the gastric wall. When there are large areas of infiltration, diffuse rugal flattening and a rigid, thickened wall may impart a leather bottle appearance termed x

Answer 13

linitis plastica

Question 14

Although extranodal lymphomas can arise in virtually any tissue, they do so most commonly in the GI tract, particularly the x.

Answer 14

stomach

*Nearly 5% of all gastric malignancies are primary lymphomas, the most common of which are indolent extranodal marginal zone B-cell lymphomas. In the gut these tumors are often referred to as lymphomas of MALT, or MALTomas.
Extranodal marginal zone B-cell lymphomas usually arise at sites of chronic inflammation.

Question 15

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the abdomen.

More than half of these tumors occur in the x.

The term stromal reflects historical confusion about the origin of this tumor, which is now recognized to arise from the interstitial cells of x

increased incidence of GIST in individuals with neurofibromatosis type x

Answer 15

stomach

Cajal, or pacemaker cells

NF1

Question 16

Approximately 75% of all GISTs have oncogenic, gainof-function mutations in the receptor x

GISTs composed of thin elongated cells are classified as x cell type

Answer 16

tyrosine kinase KIT. Most useful diagnostic marker is KIT (CD117), which is immunohistochemically detectable in Cajal cells and 95% of gastric GISTs

spindle

Recurrence or metastasis is rare for gastric GISTs smaller than 5 cm but common for mitotically active tumors larger than 10 cm.

Question 17

Celiac disease, also known as celiac sprue or glutensensitive enteropathy, is x

Answer 17

Celiac disease, also known as celiac sprue or glutensensitive enteropathy, is an immune-mediated disorder triggered by the ingestion of gluten-containing foods such as wheat, rye, or barley in genetically predisposed individuals.

Question 18

Coeliac

A characteristic itchy, blistering skin lesion, x, can be present in as many as 10% of patients.

Answer 18

dermatitis herpetiformis

Question 19

Coeliac.

The most sensitive test is the measurement of x.

Answer 19

IgA antibodies against tissue transglutaminase. (anti-tTG), IgA

IgA antiendomysial antibodies can also be present.

The absence of HLA-DQ2 and HLA-DQ8 is useful for its negative predictive value, but the presence of these alleles is not helpful in confirming the diagnosis

Question 20

Diarrhea can be characterized as x4

Answer 20

secretory, osmotic, malabsorptive, or exudative.

• Secretory diarrhea is characterized by isotonic stool and persists during fasting. E.g. V. cholerae, VIPoma
• Osmotic diarrhea, such as occurs with lactase deficiency, is due to the excessive osmotic force exerted by unabsorbed luminal solutes. The diarrhea fluid is more than 50 mOsm more concentrated than plasma, and diarrhea abates with fasting.
• Malabsorptive diarrhea follows generalized failure of nutrient absorption, is associated with steatorrhea, and is relieved by fasting. E.g. Acute radiation enteritis, atrophic gastritis, celiac
• Exudative diarrhea due to inflammatory disease is characterized by purulent, often bloody stools that continue during fasting. E.g. salmonell,shigella

Question 21

Campylobacter infection can result in reactive arthritis, primarily in patients with x

Answer 21

HLA-B27 genotype.

Other extraintestinal complications, including erythema nodosum and Guillain-Barré syndrome, a flaccid paralysis caused by immunologically mediated inflammation of peripheral nerves (Chapter 27), are not HLA-linked

Question 22

Salmonella infection causes x in the terminal ileum to enlarge into sharply delineated, plateau-like elevations up to 8 cm in diameter.

Answer 22

Peyer patches

Question 23

Patients with x are particularly susceptible to Salmonella osteomyelitis.

Answer 23

sickle cell disease

Question 24

While other organisms such as Salmonella, Clostridium perfringens type A, or Staphylococcus aureus may also produce diarrhea in the context of antibiotic therapy, only x causes pseudomembranous colitis.

Answer 24

C. difficile

Question 25

Risk factors for C. difficile–associated colitis include …

Answer 25

antibiotic treatment, advanced age, hospitalization, and immunosuppression.

Question 26

Features That Differ Between Crohn Disease and Ulcerative Colitis

Answer 26

Question 27

Extraintestinal manifestations of IBD include …

Answer 27

cutaneous nodules formed by granulomas, uveitis, migratory polyarthritis, sacroileitis, ankylosing spondylitis, erythema nodosum, cutaneous granulomas, and clubbing of the fingertips, any of which may develop before intestinal disease is recognized.

Pericholangitis and primary sclerosing cholangitis occur in individuals with Crohn disease with a higher frequency than in those without Crohn disease, but are even more common in individuals with ulcerative colitis Approximately 2.5% to 7.5% of individuals with ulcerative colitis also have primary sclerosis cholangitis

As discussed later, risk of colonic adenocarcinoma is increased in patients with long-standing colonic disease.

Question 28

Gastrointestinal Polyposis Syndromes

Answer 28

Question 29

Although most colorectal adenomas are benign lesions, a small proportion harbor invasive cancer at the time of detection.

Size is the most important characteristic that correlates with risk of malignancy. For example, while cancer is extremely rare in adenomas less than x in diameter, nearly 40% of lesions larger than x in diameter contain foci of invasive cancer.

High-grade dysplasia is also a risk factor for cancer in an individual polyp, but does not confer an increased risk of cancer in other polyps within the same patient.

Answer 29

1 cm
4 cm

Question 30

Familial adenomatous polyposis (FAP) is an x(inheritance) disorder in which patients develop numerous colorectal adenomas as teenagers.

It is caused by somatic mutations of the adenomatous polyposis coli, or APC, gene, which is a key negative regulator of the Wnt signaling pathway.

Approximately x% of cases are inherited, while the remainder appear to be caused by de novo mutations.

Answer 30

autosomal dominant
75%

At least 100 polyps are necessary for a diagnosis of classic FAP, but thousands may be presen

Question 31

Colorectal adenocarcinoma develops in 100% of untreated FAP patients, often before age x and nearly always by age x.

Answer 31

30
50

Question 32

Colectomy prevents colorectal cancer, but patients remain at risk for neoplasia at other sites.

The x and x are common extracolonic sites of adenomas in FAP patients.

Answer 32

ampulla of Vater
stomach

Question 33

Common Patterns of Sporadic and Familial Colorectal Neoplasia

Answer 33

Question 34

HNPCC is caused by x

Often located in the x colon

There are at least five mismatch repair genes, but the majority of patients with HNPCC have mutations in …

Answer 34

inherited mutations in mismatch repair genes that encode proteins responsible for the detection, excision, and repair of errors that occur during DNA replication

Often located in the right colon

There are at least five mismatch repair genes, but the majority of patients with HNPCC have mutations in MSH2 or MLH1.

Question 35

Colon adenocarcinomas, the two most important prognostic factors are …

Answer 35

depth of invasion and the presence of lymph node metastases.

Invasion into the muscularis propria significantly reduces the probability of survival, which is decreased further by the presence of lymph node metastases

Question 36

Intestinal polyps can be classified as nonneoplastic or neoplastic.

The nonneoplastic polyps can be further subclassified as …

Benign epithelial neoplastic polyps of the intestines are termed adenomas. The hallmark of these lesions, which are the precursors of colonic adenocarcinomas, is …

Answer 36

hyperplastic, inflammatory, or hamartomatous

cytologic dysplasia

Question 37

APC/β-catenin pathway, which is activated in the classic adenoma-carcinoma sequence

Answer 37

The classic adenoma-carcinoma sequence accounts for up to 80% of sporadic cancers and typically includes mutation of APC early in the neoplastic process

Both copies of the APC gene must be functionally inactivated, either by mutation or by epigenetic events, for adenomas to develop. The APC protein normally binds to and promotes degradation of β-catenin, a component of the Wnt signaling pathway. With loss of APC function, β-catenin accumulates and and activate Wnt signaling

Other changes, including mutation of KRAS, losses at 18q21 involving SMAD2 and SMAD4, and inactivation of the tumor suppressor gene TP53, lead to the emergence of carcinoma.

Question 38

MSI pathway, which is associated with defects in DNA mismatch repair and accumulation of mutations in microsatellite repeat regions of the genome

Answer 38

Morphologic and molecular changes in the mismatch repair pathway of colon carcinogenesis. Defects in mismatch repair genes result in microsatellite instability and permit accumulation of mutations in numerous genes. If these mutations affect genes involved in cell survival and proliferation, cancer may develop.

MLH1, MSH2
TGFBR2, BAX, BRAF, TCF4, IGF2R, others

Question 39

The anal canal can be divided into thirds.

What are they + ?epithelium

Answer 39

The upper zone is lined by columnar rectal epithelium; the middle third by transitional epithelium; and the lower third by stratified squamous epithelium.

Question 40

Diagnosis of acute appendicitis requires neutrophilic infiltration of the x.

Answer 40

muscularis propria

Question 41

Acute liver failure is defined as an acute liver illness associated with encephalopathy and coagulopathy that occurs within x weeks of the initial liver injury in the absence of preexisting liver disease.

Answer 41

26

Question 42

Accidental or deliberate ingestion of acetaminophen accounts for almost x% of adult cases in the United States, while autoimmune hepatitis, other drugs/toxins, and acute hepatitis A and B infections account for most remaining cases.

In Asia, acute hepatitis x&x are the predominant causes.

Answer 42

50%

B and E

Question 43

manifestations of acute liver failure are as follows:

Answer 43

liver enlarged, then shrinkage
Cholestasis
Hepatic encephalopathy
Coagulopathy:Easy bruisability is an early sign, which can progress to life-threatening or fatal intracranial bleeding.
Portal hypertension
Hepatorenal syndrome is a form of renal failure occurring in individuals with liver failure

Question 44

The leading causes of chronic liver failure worldwide are …

Answer 44

chronic hepatitis B, chronic hepatitis C, nonalcoholic fatty liver disease, and alcoholic liver disease.

Question 45

Location and Causes of Portal Hypertension

Answer 45

Question 46

The four major consequences of portal hypertension are

Answer 46

(1) hepatic encephalopathy (described under liver failure), (2) ascites, (3) the formation of portosystemic venous shunts, and (4) congestive splenomegaly.

Question 47

Portosystemic Shunts

Answer 47

The principal sites are veins around and within the rectum (manifest as hemorrhoids), the esophagogastric junction (producing varices), the retroperitoneum, and the falciform ligament of the liver (involving periumbilical and abdominal wall collaterals). Abdominal wall collaterals appear as dilated subcutaneous veins extending from the umbilicus toward the rib margins (caput medusae)

Question 48

The mnemonic for causes of acute liver failure is as follows:

Answer 48

• A: Acetaminophen, hepatitis A, autoimmune hepatitis
• B: Hepatitis B
• C: Hepatitis C, cryptogenic
• D: Drugs/toxins, hepatitis D
• E: Hepatitis E, esoteric causes (e.g.,Wilson disease, Budd-Chiari syndrome, lymphoma, carcinoma)
• F: Fatty change of the microvesicular type (e.g., fatty liver of pregnancy, valproate, tetracycline, Reye syndrome)

Question 49

Potential outcomes of hepatitis B infection in adults

Answer 49

Question 50

Hepatitis C Virus (HCV) x causes symptomatic acute hepatitis, but it is the x cause of chronic viral hepatitis.

Answer 50

rarely
most common

Question 51

Hepatitis viruses
% progress to chronic

Answer 51

Question 52

Viral hepatitis accounts for a mately 10% of cases of acute hepatic failure. Hepatitis x and x are the most common causes worldwide, while HBV is more common in Asia and the Mediterranean.

Answer 52

A and E

Question 53

The diagnosis of autoimmune hepatitis is based on the combination of four features: …

gender prediliction

Answer 53

autoantibodies, elevation of serum IgG, exclusion of other etiologies (e.g., viral hepatitis, drugs), and supportive histologic findings on liver biopsy.

Autoimmune hepatitis is a chronic, progressive hepatitis associated with genetic predisposition, autoantibodies, and therapeutic response to immunosuppression. There is a female predominance (78%).

The most common autoantibodies in type 1 autoimmune hepatitis are ANAs and anti–smooth muscle antibodies (ASMAs), while type 2 autoimmune hepatitis is characterized by anti-LKM1 autoantibodies.

Question 54

There are two mechanisms of liver injury:

• x a dose-dependent phenomenon of the drug, or its metabolite, which predictably affects exposed individuals, a typical example being acetaminophen, which is the most common cause of acute liver failure in the United States. example?
• x which is not dosedependent, accounts for the majority of drug-induced liver injury, but typically occurs in a minority of individuals.

Answer 54

Direct hepatotoxicity

Idiosyncratic (hypersensitivity) response

A classic, dose-dependent, predictable hepatotoxin is acetaminophen, now the most common cause of acute liver failure necessitating transplantation in the United States.

Question 55

Drug induced liver injury, examples?

Answer 55

Alcohol
Oral contraceptive
Vinyl chloride
Chemo agents

Some agents produce other patterns of injury.

Drugs like amiodarone (antiarrhythmic), tamoxifen (anti-estrogen), irinotecan (antineoplastic), and methotrexate (immunosuppressive) can cause a steatohepatitis-like pattern of injury.

Mitochondrial dysfunction caused by drugs such as tetracycline (antibiotic), valproic acid (anticonvulsant), and zidovudine (antiretroviral) can result in microvesicular steatosis.

Endothelial injury to sinusoids and central veins can be caused by cytotoxic agents (azathioprine, oxaliplatin), leading to sinusoidal obstruction syndrome (formerly called veno-occlusive disease).

Question 56

In contrast to other chronic liver diseases, in which serum xc tends to be higher than serum x, in alcoholic liver disease serum x tend to be higher than serum x levels by a ratio of 2 : 1 or greater.

Answer 56

In contrast to other chronic liver diseases, in which serum ALT tends to be higher than serum AST, in alcoholic liver disease serum AST tend to be higher than serum ALT levels by a ratio of 2 : 1 or greater.

Question 57

Consumption of x g/day of alcohol is considered to be the threshold for development of alcoholic liver disease, but may be lower in women.

Answer 57

80

• It may take 10 to 15 years of drinking for development of cirrhosis, which occurs only in a small proportion of chronic alcoholics.
• The pathologic effects of alcohol on hepatocytes include changes in lipid metabolism related to altered redox potential, injury caused by ROS generated by metabolism of alcohol by the P450 system, and protein adducts formed by acetaldehyde, a major metabolite of alcohol.

Question 58

World Health Organization Criteria for the Metabolic Syndrome

Answer 58

Question 59

Hemochromatosis is caused by excessive iron absorption, most of which is deposited in the liver and x, followed by the

Answer 59

liver, pancreas, myocardium, pituitary gland, adrenal gland, thyroid and parathyroid glands, joints, and skin

Question 60

The following features characterize severe iron overload:

Answer 60

• Fully developed cases exhibit (1) micronodular cirrhosis (all patients); (2) diabetes mellitus (75% to 80% of patients); and (3) abnormal skin pigmentation (75% to 80% of patients).
• Iron accumulation in hereditary forms is lifelong, but the injury caused by excessive iron is slow and progressive; hence symptoms usually first appear in the fourth to fifth decades of life in men and later in women since menstrual bleeding counterbalances the accumulation until menopause.
• Because many women do not accumulate clinically relevant amounts of iron within their lifetime, hereditary hemochromatosis affects more males than females (ratio of 5 to 7 : 1).

Question 61

The main regulator of iron absorption is the protein x, encoded by the HAMP gene and produced and secreted by the liver

The adult form of hereditary hemochromatosis is usually caused by mutations of x

Answer 61

hepcidin

HFE

Question 61

The main regulator of iron absorption is the protein x, encoded by the HAMP gene and produced and secreted by the liver

The adult form of hereditary hemochromatosis is usually caused by mutations of x

Answer 61

hepcidin

HFE

Question 61

The main regulator of iron absorption is the protein x, encoded by the HAMP gene and produced and secreted by the liver

The adult form of hereditary hemochromatosis is usually caused by mutations of x

Answer 61

hepcidin

HFE

Question 62

Haemachromatosis
Another significant cause of death is hepatocellular carcinoma; the risk is x-fold greater than in the general population.

Answer 62

200

Question 63

Hemochromatosis
Death may result from cirrhosis or cardiac disease.
Another significant cause of death is hepatocellular carcinoma; the risk is x-fold greater than in the general population.

Answer 63

200

Question 64

The most common causes of secondary (or acquired) hemochromatosis are disorders associated with ineffective erythropoiesis, such as x and x

In these disorders, the excess iron results not only from transfusions, but also from increased absorption.

Answer 64

thalassemia
myelodysplastic syndrome.

Question 65

The general notation is “Pi” for “protease inhibitor” and an alphabetic letter for the position in the gel; two letters denote the genotype of an individual’s two alleles.

The most common genotype is x, occurring in 90% of individuals (the “wild type”).

The most common clinically significant mutation is x

Answer 65

PiMM
PiZ

homozygotes for the PiZZ protein have circulating α1 AT levels that are only 10% of normal. These individuals are at high risk for developing clinical disease. Expression of alleles is autosomal codominant, and, consequently, PiMZ heterozygotes have intermediate plasma levels of α1 AT. Among people of northern European descent, the PiZZ state affects 1 in 1800 live births. Because of its early presentation with liver disease, α1 AT deficiency is the most commonly diagnosed inherited hepatic disorder in infants and children.

Question 66

The “rule of 2’s” is often used to help remember characteristics of Meckel diverticula, which:

Answer 66

• Occur in approximately 2% of the population
• Are generally present within 2 feet (60 cm) of the ileocecal valve
• Are approximately 2 inches (5 cm) long
• Are twice as common in males
• Are most often symptomatic by age 2 (only approximately 4% are ever symptomatic).

Question 67

PBC is an autoimmune disease characterized by inflammatory destruction of x intrahepatic bile ducts.

Gender ratio

Answer 67

small- and medium-sized

Large intrahepatic ducts and the extrahepatic biliary tree are not involved. Most patients are diagnosed in the early stages of disease, and hence the former name “primary biliary cirrhosis” is no longer used. PBC has a striking female predilection of 9 : 1, with a peak incidence between 40 and 50 years of age.

Question 68

Main Features of Primary Biliary Cholangitis and Primary Sclerosing Cholangitis

Answer 68

Question 69

The histologic picture of lymphocytic and/or granulomatous bile duct destruction (florid duct lesion) is highly characteristic of x

Answer 69

PBC

Question 70

PSC is characterized by inflammation and obliterative fibrosis of x and dilation of preserved segments.

Age and gender

Answer 70

extrahepatic and large intrahepatic ducts

PSC tends to occur in the third through fifth decades and has a 2 : 1 male predominance.

Question 71

Cancer associated with PSC

Answer 71

cholangiocarcinoma, 20% lifetime risk

Question 72

Inflammatory bowel disease, particularly ulcerative colitis, affects approximately x% of individuals with PSC, whereas x% of inflammatory bowel disease patients develop PSC.

Answer 72

70%
8%

Question 73

Budd Chiari causes

Answer 73

Hepatic vein thrombosis is associated with myeloproliferative neoplasms such as polycythemia vera, inherited disorders of coagulation, antiphospholipid antibody syndrome, paroxysmal nocturnal hemoglobinuria, and intraabdominal cancers, particularly hepatocellular carcinoma.

In pregnancy or with oral contraceptive use, it occurs through interaction with an underlying thrombophilic disorder.

Question 74

FNH is well circumscribed, typically lacks a capsule, and has a central x in up to 80% of cases

Gender

Answer 74

stellate scar

F>M

Question 75

biliary hamartoma (x complex)

Answer 75

von Meyenburg

Question 76

x is the most common benign liver tumor.

Answer 76

Cavernous hemangioma

Question 77

Hepatocellular adenoma is a benign neoplasm that typically occurs in x and is strongly associated with use of x and x

Answer 77

young women
oral contraceptives and anabolic steroids.

Question 78

x is the most common liver tumor of early childhood.

Age range?

Answer 78

Hepatoblastoma

It rarely occurs over the age of 3 years, and its incidence is increasing.

The overall 5-year survival rate is approximately 80%.

Question 79

Most HCCs occur in the setting of chronic liver disease with cirrhosis, while % arise in noncirrhotic livers

One unusual histologic subtype that often occurs in adolescents and young adults in the absence of preexisting liver disease, x, is strongly associated with a fusion gene that leads to aberrant activity of protein kinase A, an enzyme that participates in a signaling pathway regulated by cAMP.

Answer 79

15% to 20%

fibrolamellar HCC

Question 80

True or False

Nonalcoholic fatty liver disease also increases the risk of HCC, even in the absence of cirrhosis.

Answer 80

True

Question 81

Adenocarcinomas arising from the intrahepatic biliary tree are referred to as intrahepatic cholangiocarcinoma, while similar tumor arising from the extrahepatic bile ducts are referred to as x

Answer 81

biliary adenocarcinoma.

Question 82

Risk factors for cholangiocarcinoma

Lymph node metastasis is present in x% of patients at presentation.

Answer 82

Developmental disorders, like fibropolycystic liver disease, and chronic inflammatory conditions involving the bile ducts, including primary sclerosing cholangitis, infestation by liver flukes (particularly Opisthorchis and Clonorchis species), and hepatolithiasis are risk factors for biliary tract neoplasms. Chronic liver diseases that predispose to HCC, such as hepatitis B, hepatitis C, and nonalcoholic fatty liver disease, also increase the risk for intrahepatic cholangiocarcinoma. As with HCC, chronic injury, inflammation, and regeneration of biliary epithelium in these conditions may set the stage for acquisition of driver mutations leading to cancer.

Intrahepatic cholangiocarcinoma usually occurs in the noncirrhotic liver

50% to 60%

Question 83

Extrahepatic biliary adenocarcinomas include perihilar tumors known as x, which are located at the junction of the right and left hepatic ducts. These tumors comprise 60% to 70% of extrahepatic biliary adenocarcinomas, while the remaining 30% to 40% involve the common bile duct.

Answer 83

Klatskin tumors

Question 84

Risk Factors for Gallstones

Answer 84

Question 85

T or F
Gallstones also are associated with an increased risk of gallbladder carcinoma

Answer 85

T

Question 86

Outpouchings of the mucosal epithelium through the wall (Rokitansky-Aschoff sinuses) may be quite prominent in ?

Answer 86

chronic choleycystitis

xanthogranulomatous cholecystitis, the gallbladder has a massively thickened wall and is shrunken, nodular, and chronically inflamed with foci of necrosis and hemorrhage. It is triggered by rupture of Rokitansky-Aschoff sinuses into the wall of the gallbladder followed by an accumulation of macrophages that have ingested biliary phospholipids.

Question 87

x is the most common malignancy of the extrahepatic biliary tract.

Answer 87

Carcinoma of the gallbladder

Question 88

Etiologic Factors in Acute Pancreatitis

Answer 88

Question 89

x (chromosome 12p) is the most frequently altered oncogene in pancreatic cancer, with activating point mutations present in greater than 90% of cases.

Answer 89

KRAS

Question 90

Glomerular diseases presenting with a nephritic syndrome are characterized by inflammation in the glomeruli. The main clinical features of nephritic syndrome include the following:

Answer 90

• Hematuria (red blood cells and red cell casts in urine)
• Proteinuria (usually subnephrotic range) with or without edema
• Azotemia
• Hypertension

Question 91

Major Primary Glomerulonephritides

Answer 91

Question 92

PSGS
More than x% of affected children eventually recover renal function with conservative therapy aimed at maintaining sodium and water balance. A small minority of children (perhaps less than 1%) do not improve, become severely oliguric, and develop a rapidly progressive form of glomerulonephritis (described later)

Answer 92

95%

~60% adults

Question 93

Nephrotic syndrome is caused by a derangement in glomerular capillary walls resulting in increased permeability to plasma proteins. The manifestations of the syndrome include the following:

Answer 93

• Massive proteinuria, with the daily loss of 3.5 g or more of protein (less in children)
• Hypoalbuminemia, with plasma albumin levels less than 3 g/dL
• Generalized edema
• Hyperlipidemia and lipiduria

Question 94

The glomeruli are large and hypercellular. The hypercellularity is produced both by proliferation of cells in the mesangium and so-called endocapillary proliferation involving capillary endothelium and infiltrating leukocytes. The glomeruli have an accentuated “lobular” appearance due to the proliferating mesangial cells and increased mesangial matrix (Fig. 20.16). The GBM is thickened, and often shows a “double-contour” or “tramtrack” appearance, especially evident in silver or PAS stains. This is caused by “duplication” of the basement membrane (also commonly referred to as splitting), usually as the result of new basement membrane synthesis in response to subendothelial deposits of immune complexes. Between the duplicated basement membranes, there is inclusion or interposition of cellular elements, which can be of mesangial, endothelial, or leukocytic origin. Such interposition also gives rise to the appearance of “split” basement

Answer 94

MPGN

Question 95

x, characterized by mesangial deposits of x containing immune complexes, is the most common cause of glomerulonephritis worldwide.

Answer 95

IgA nephropathy

IgA containing immune complexes

Question 96

ATI can be caused by a variety of conditions, including the following:

Answer 96

• Ischemia, due to decreased or interrupted blood flow. Examples include diffuse involvement of the intrarenal blood vessels such as in microscopic polyangiitis, microangiopathies (e.g., hemolytic uremic syndrome [HUS] or thrombotic thrombocytopenic purpura [TTP]), or decreased effective circulating blood volume, as occurs in hypovolemic shock
• Direct toxic injury to the tubules. This may be caused by endogenous agents, e.g., myoglobin, hemoglobin, monoclonal light chains, bile/bilirubin, or exogenous agents, e.g., drugs, radiocontrast dyes, heavy metals, organic solvents.

Question 97

Causes of Tubulointerstitial Nephritis

Answer 97

Question 98

Causes of Papillary Necrosis

Answer 98

Question 99

Summary of Renal Cystic Diseases

Answer 99

Question 100

ESRD who have undergone prolonged dialysis. There is up to x-fold increased risk of renal cell carcinoma, which develops in 7% of patients observed for 10 years.

Answer 100

100

Question 101

Prevalence of Various Types of Renal Stones

Answer 101

Question 102

Angiomyolipomas are present in x% of patients with tuberous sclerosis.

?clinical importance

Answer 102

25% to 50%

The clinical importance of angiomyolipoma is due largely to their susceptibility to spontaneous hemorrhage.

Question 103

Benign Renal Neoplasms

Answer 103

Renal papillary adenoma
Angiomyolipoma
Oncocytoma

Question 104

RCC risk factors

Answer 104

Cigarette smokers have double the incidence of renal cell carcinoma, and pipe and cigar smokers are also more susceptible

obesity (particularly in women); hypertension; unopposed estrogen therapy; and exposure to asbestos, petroleum products, and heavy metals. There is also an increased risk in patients with ESRD, chronic kidney disease, acquired cystic disease (see earlier), and tuberous sclerosis.

Question 105

The classification of renal cell carcinoma is based on correlative cytogenetic, genetic, and histologic studies of both familial and sporadic tumors. The major types of tumor are as follows

Answer 105

Clear cell carcinoma. This is the most common type, accounting for 70% to 80% of renal cell cancers. 95% sporadic

Papillary carcinoma accounts for 10% to 15% of renal cancers. Unlike clear cell carcinomas, papillary carcinomas are frequently multifocal in origin.

Chromophobe carcinoma represents 5% of renal cell cancers and is composed of cells with prominent cell membranes and pale eosinophilic cytoplasm, usually with a halo around the nucleus. Like the benign oncocytoma, they are thought to grow from intercalated cells of collecting ducts and have an excellent prognosis compared with that of the clear cell and papillary cancers. Histologic distinction from oncocytoma can be difficult.

Collecting duct (Bellini duct) carcinoma represents a mately 1% or less of renal epithelial neoplasms

Question 106

In x% of new patients with renal cell carcinoma, there is radiologic evidence of metastases at the time of presentation.

The most common locations of metastasis are the x

Answer 106

15%

lungs (more than 50%) and bones (33%), followed in frequency by the regional lymph nodes, liver, adrenal glands, and brain.

Question 107

The risk of Wilms tumor is increased with at least three recognizable groups of congenital malformations associated with distinct chromosomal loci

Answer 107

The first group of patients has the WAGR syndrome, characterized by Wilms tumor, aniridia, genitourinary anomalies, and intellectual disability (formerly called mental retardation). Their lifetime risk of developing Wilms tumor is approximately 33%.

A second group of patients at much higher risk for Wilms tumor (~90%) has Denys-Drash syndrome, which is characterized by gonadal dysgenesis (male pseudohermaphroditism) and early-onset nephropathy leading to renal failure.

A third group with an increased risk of developing Wilms tumor consists of children with Beckwith-Wiedemann syndrome (BWS), characterized by enlargement of body organs (organomegaly), macroglossia, hemihypertrophy, omphalocele, and abnormal large cells in the adrenal cortex (adrenal cytomegaly).

Question 108

Wilms Tumor

The classic x combination of blastemal, stromal, and epithelial cell types is observed in the vast majority of lesions

Answer 108

triphasic

Question 109

Nephrogenic rests are putative precursor lesions of Wilms tumors and are seen in the renal parenchyma adjacent to approximately 25% to 40% of unilateral tumors; this frequency rises to nearly x% in cases of bilateral Wilms tumors.

Answer 109

100%

Question 110

Congenital Anomalies of Ureter

Answer 110

Question 111

Major Causes of Ureteral Obstruction

Answer 111

Question 112

Cytotoxic agents, such as x, may cause hemorrhagic cystitis.

Answer 112

cyclophosphamide

Question 113

Cystitis glandularis and cystitis cystica.

These are common lesions of the urinary bladder in which nests of urothelium (von Brunn nests) grow downward into the x. Here, epithelial cells in the center of the nest undergo x and take on a cuboidal or columnar appearance (cystitis glandularis) or retract to produce cystic spaces lined by flattened urothelium (cystitis cystica).

Answer 113

lamina propria
metaplasia

Extensive and multifocal intestinal metaplasia is a precursor to adenocarcinoma.

Question 114

A classic example of this sequence is seen with bladder x, which commonly produces squamous metaplasia and is associated with squamous cell carcinoma in areas in which it is endemic.

Answer 114

schistosomiasis

Question 115

There are two distinct precursor lesions to invasive urothelial carcinoma: …

Answer 115

noninvasive papillary tumors
flat noninvasive urothelial carcinoma in situ (CIS)

Question 116

Tumors of the Urinary Bladder

Answer 116

Question 117

Bladder cancer
Although invasion into the lamina propria worsens the prognosis, the major decrease in survival is associated with invasion of the x

Answer 117

muscularis propria (detrusor muscle).

Question 118

Several factors have been implicated in the causation of urothelial carcinoma, including the following:

Answer 118

Cigarette smoking is clearly the most important influence, increasing the risk threefold to sevenfold, depending on the duration and type of tobacco use. Between 50% and 80% of all bladder cancers among men are associated with the use of cigarettes

Industrial exposure to aryl amines, particularly 2-naphthylamine and related compounds

Schistosoma haematobium infections in endemic areas (Egypt, Sudan) are an established risk.

Long-term use of analgesics is implicated, as it is in analgesic nephropathy

Heavy long-term exposure to cyclophosphamide, an immunosuppressive agent, induces, as noted, hemorrhagic cystitis and increases the risk of bladder cancer.
Irradiation, often administered for other pelvic malignancies, increases the risk of urothelial carcinoma occurring several years following exposure.

Question 119

Cervical cancer

If untreated, x% of CIS progresses to invasive cancer.

Answer 119

50% to 75%

Question 120

Several, including tuberculosis and gonorrhea, arise first in the epididymis and only involve the testis secondarily, while others, such as x, involve the testis first.

Answer 120

syphilis

Question 121

Mumps is a systemic viral disease that most commonly affects school-aged children. Testicular involvement is extremely x in this age group. In postpubertal males, orchitis occurs in 20% to 30% of cases. Most often, acute interstitial orchitis develops 1 week after the onset of swelling of the parotid glands.

Answer 121

uncommon

Question 122

Testicular cancer. x predominantly affect Caucasian males between 15 and 45 years of age and are the most common cancer in this age group.

Answer 122

Germ Cell Tumors

Seminoma is the most common type of GCT, making up about 50% of these tumors overall.

Spermatocytic tumors are uncommon, representing 1% to 2% of all testicular germ cell neoplasms. In contrast to other GCTs, affected individuals are generally older (usual more than 65 years old). This slow-growing tumor does not metastasize, and when treated by surgical resection it has an excellent prognosis.

Question 123

Pathologic Classification of Common Testicular Tumors

Answer 123

Question 124

The peak incidence for x carcinoma is in the 20- to 30-year-old age group, about a decade earlier than that of seminoma. x carcinoma is more aggressive than seminoma and may occur as a pure tumor or mixed with other germ cell components.

x, prepubertal yolk sac tumors are the most common testicular tumor in infants and children up to 3 years of age. In this age group it has a very good prognosis

Answer 124

embryonal
Yolk Sac Tumor, also known as endodermal sinus tumor

Question 125

The most common benign paratesticular tumor is x tumor.

Answer 125

adenomatoid

The most common malignant paratesticular tumors are rhabdomyosarcomas in children and liposarcomas in adults

Question 126

Clinically, testicular GCTs are divided into two groups: seminomas and nonseminomatous tumors.

Seminomas spread mainly to x

Nonseminomatous tumors tend to spread x

Answer 126

para-aortic nodes and are radiosensitive.

earlier via lymphatic and hematogenous routes.

Question 127

x, the most common form of prostatitis, is often referred to clinically as x

Answer 127

Chronic abacterial prostatitis

chronic pelvic pain syndrome.

Question 128

BPH
x is the main androgen in the prostate, where it is formed from testosterone through the action of type 2 5α-reductase

Answer 128

Dihydrotestosterone (DHT)

BPH is found in up to 90% of men by age 80.

Question 129

Based on autopsy studies, the incidence of prostate cancer increases from 20% in men in their 50s to approximately x% in men between the ages of 70 and 80 years.

Answer 129

70%

Question 130

The most common driver mutations in prostate cancer are gene rearrangements that result in androgen dependent overexpression of x family transcription factors, most commonly ERG or ETV1.

Answer 130

Ets

Question 131

The syndromes of adrenal hyperfunction are caused by overproduction of the three major hormones of the adrenal cortex

Answer 131

(1) Cushing syndrome, characterized by an excess of cortisol;

(2) hyperaldosteronism as a result of excessive aldosterone

(3) adrenogenital or virilizing syndromes caused by an excess of androgens.

Question 132

x account for 60% to 70% of cases of endogenous hypercortisolism.

Answer 132

ACTH-secreting pituitary adenomas

Question 133

The adrenal glands in individuals with Cushing disease are characterized by variable degrees of x caused by the elevated levels of ACTH. x, in turn, is responsible for hypercortisolism.

Answer 133

nodular cortical hyperplasia

The cortical hyperplasia

Question 134

Secretion of ectopic ACTH by nonpituitary tumors accounts for about 5% to 10% of ACTH-dependent Cushing syndrome cases. In many instances, the responsible tumor is x

Answer 134

small-cell carcinoma of the lung, although other neoplasms, including carcinoids, medullary carcinomas of the thyroid, and PanNETs, have been associated with the syndrome.

Question 135

Primary adrenal neoplasms, such as x (~10% to 20%) and x (~5% to 7%) are the most common underlying causes of ACTH-independent Cushing syndrome.

The biochemical sine qua non of ACTHindependent Cushing syndrome is x serum levels of cortisol with x levels of ACTH.

Answer 135

adrenal adenoma
carcinoma

elevated
low

Question 136

Causes of Endogenous Cushing Syndrome

Answer 136

Question 137

In patients in whom the syndrome results from exogenous glucocorticoids, suppression of endogenous ACTH results in x (changes in adrenal), due to a lack of stimulation of the zonae fasciculata and reticularis by ACTH. The zona glomerulosa is of normal thickness in such cases, because this portion of the cortex functions independently of ACTH.

Answer 137

bilateral cortical atrophy

Question 138

Clinical Features of Cushing Syndrome

Answer 138

Question 139

Primary hyperaldosteronism is caused by one of three conditions:

resultant hypertension, suppression of the renin-angiotensin system, and decreased plasma renin activity

Answer 139

1. Bilateral idiopathic hyperaldosteronism, characterized by bilateral nodular hyperplasia of aldosterone-secreting zona glomerulosa cells of the adrenal glands, is the most common underlying cause, accounting for about 60% of cases, most of which are sporadic.
2. Adrenocortical neoplasm, either an aldosterone-producing adenoma (the most common cause) or, rarely, an adrenocortical carcinoma. In approximately 35% of cases, primary hyperaldosteronism is caused by a solitary aldosterone-secreting adenoma, a condition referred to as Conn syndrome.
3. Familial hyperaldosteronism accounts for ~5% of cases.

Question 140

In secondary hyperaldosteronism, aldosterone release occurs in response to activation of the reninangiotensin system

It is characterized by increased levels of plasma renin and is encountered in conditions such as the following:

Answer 140

• Decreased renal perfusion (arteriolar nephrosclerosis, renal artery stenosis)
• Arterial hypovolemia and edema (congestive heart failure, cirrhosis, nephrotic syndrome)
• Pregnancy (due to estrogen-induced increases in plasma renin substrate)

Question 141

Three major patterns of adrenocortical insufficiency are recognized:

Answer 141

(1) primary acute adrenocortical insufficiency (adrenal crisis) i.e acute stress, sudden withdrawal of steroids, massive adrenal haemorrhage in DIC and Waterhouse-Friderichsen syndrome.
(2) primary chronic adrenocortical insufficiency (Addison disease): Addison disease, or chronic adrenocortical insufficiency, is an uncommon disorder resulting from progressive destruction of the adrenal cortex.
(3) secondary adrenocortical insufficiency.

Question 142

Adrenocortical Insufficiency

Answer 142

Question 143

A large number of diseases may affect the adrenal cortex, including lymphoma, amyloidosis, sarcoidosis, hemochromatosis, fungal infections, and adrenal hemorrhage, but more than 90% of all cases are attributable to one of four disorders: …

Answer 143

autoimmune adrenalitis, tuberculosis, AIDS, or metastatic cancers.

Autoimmune adrenalitis accounts for 80% to 90% of cases of primary adrenal insufficiency in high-income countries.

Question 144

The most important diseases of the adrenal medulla are neoplasms, which include neoplasms of chromaffin cells (x) and neuronal neoplasms (x).

Answer 144

pheochromocytomas
neuroblastic tumors

Question 145

Traditionally, the features of pheochromocytomas have been summarized by the “rule of 10s”.

Answer 145

• Ten percent of pheochromocytomas are extra-adrenal, occurring in sites such as the organs of Zuckerkandl and the carotid body. Pheochromocytomas that develop in extra-adrenal paraganglia are designated paragangliomas
• Ten percent of sporadic adrenal pheochromocytomas are bilateral; this figure may rise to as high as 50% in cases that are associated with familial tumor syndromes (see later).
• Ten percent of adrenal pheochromocytomas are biologically malignant, defined by the presence of metastatic disease. Malignancy is more common (20% to 40%) in extra-adrenal paragangliomas, and in tumors arising in the setting of certain germline mutations.
• Ten percent of adrenal pheochromocytomas are not associated with hypertension. Of the 90% that present with hypertension, approximately two-thirds have “paroxysmal” episodes associated with a sudden rise in blood pressure and palpitations, which can, on occasion, be fatal.

Question 146

Familial Syndromes Associated With Pheochromocytoma and Extra-Adrenal Paragangliomas

Answer 146

Question 147

The definitive diagnosis of malignancy in pheochromocytomas is based exclusively x

Answer 147

on the presence of metastases.