LIVER PATHOLOGY

Ischemic bowel disease is seen particularly in patients older than 70 years, has afemale>male distribution, and presents
with crampy abdominal pain and bloody diarrhea. It involves thewatershed zones: 1) splenic flexure (involves the superior and
inferior mesenteric arteries), and 2) sigmoid (involves the inferior mesenteric, pudendal, and iliac arteries). Hypoperfusion or
occlusion of these vessels (thrombus, embolism, or stenosis) causes focal ischemic colitis. Our patient has a history of
hypercholesterolemia and cardiovascular ischemia, which suggests atherosclerosis of the affected vessels as the cause.
Gluten sensitivity (choice B) is associated with celiac disease. It affects the second part of the duodenum and the proximal
jejunum, not the colon. Patients (10%) may also have a dermatitis herpetiformis. Endoscopically, there is mucosal erythema and
atrophy. It clinically can be seen in children and adults (age 30-60 years). Atrophy of intestinal villi leads to malabsorption and weight
loss. Histologically, there is villous atrophy and lymphocytic infiltrate.
Protozoal infection (choice C) may indicate amoebic dysentery, which can be due to ingestion of infective cysts in contaminated
water or foods. Patients may be asymptomatic or symptomatic (presents with abdominal pain and bloody diarrhea). There would be
diffuse colonic involvement rather than being limited to the splenic flexure. Colonoscopy may reveal small ulcers. Histologically, there
are flask shaped ulcers and acute inflammation. Liver abscesses may also occur. Our patient denies a travel history and the focal
location does not correlate with amoebic dysentery.
Structural weakening (choice D) suggests diverticulosis, which are acquired outpouchings of colonic mucosa. It commonly
affects adults older than 60 years and the left side of the colon (sigmoid, not the splenic flexure) in Western countries and right-side
involvement in Asia and Africa (for unknown reasons). Clinically, there can be alternating constipation and diarrhea, and episodic crampy
abdominal pain (need to distinguish from irritable bowel syndrome). Impaction of a fecalith may cause diverticulitis with pain, bleeding,
and potential rupture. High fiber diet can help reduce stool bulk.
Vascular malformation (choice E) suggests angiodysplasia, dilated, malformed submucosal and mucosal vessels, which are prone to
rupture and significant bleeding. It can present as acute or intermittent bleeding and commonly occurs in the cecum or right colon and
in patients older than 60 years. Although not common, it accounts for approximately 20% of lower intestinal hemorrhage. They can
also be associated with Osler-Weber-Rendu and CREST syndrome. Our patient distinctly has mucosal ulcerations rather than prominent
mucosal vessels, and the location does not correspond to angiodysplasia.
The patient has Zollinger-Ellison syndrome (ZES), which is caused by a gastrin-secreting tumor (gastrinoma) typically located in the
pancreas or duodenal wall. Gastrinomas are MEN1 tumors that secrete the GI hormone gastrin in an unregulated manner.
Gastrin is normally produced by G-cells located in the gastric antrum or duodenum, its physiologic role being to stimulate gastric acid
production by parietal cells. Gastrin production is normally subject to negative feedback regulation by two other GI
hormones, somatostatin and secretin. Because gastrinomas are not subject to this feedback regulation, fasting gastrin levels and
gastric acid production in ZES patients is typically elevated, resulting in peptic ulcers and diarrhea. While ZES is strongly suspected in
patients with elevated gastrin levels, the test is not diagnostic, however. The secretin stimulation test is used to differentiate ZES from
other causes of hypergastrinemia. Whereas secretin injection inhibits gastrin production in a healthy individual, it causes a
marked increase in serum gastrin in patients with ZES. The physiologic mechanism remains unclear.
A secretin stimulation test involves rapid (over ~ 1 min) intravenous infusion of 2 units/kg secretin. Serum gastrin levels are measured at
various times for 30 minutes after injection. An increase in serum gastrin of more than 200 ng/mL is diagnostic for ZES.
Cholecystokinin (CCK, choice A) is a peptide hormone secreted by I cells in the small intestine. It normally stimulatesgall bladder
contraction, facilitates bile secretion, and stimulates pancreatic enzyme secretion.
Gastric inhibitory peptide (GIP, also known as glucose-dependent insulinotropic peptide, choice B) is released by K cells in
duodenum and jejunum. It stimulates insulin release from the endocrine pancreas, although it can also decrease gastric acid secretion
at sufficiently high levels.
Motilin (choice C) is a hormone secreted by M cells that enhances peristalsis in the small intestine. It has an important role in
facilitating migrating myoelectric complexes, which begin in the stomach during the a fasting state and drive a peristaltic wave that
clears residual intestinal contents (indigestible particles, bacteria, cells that have been shed from the mucosa) from the GI tract in
preparation for the next meal.
Pentagastrin (choice D) is a synthetic peptide that stimulates gastric acid production by binding to the gastrin CCKBreceptor on parietal
cells. Although up to 40% of pancreatic gastrinoma cells contain CCK B receptors, and therefore can respond to either CCK or to gastrin
itself, pentagastrin has minimal effects on gastrin secretion and response to its infusion is not reliable as a clinical test.
This patient has MEN I syndrome (parathyroid adenoma, pancreatic islet cell tumor-gastrinoma/Zollinger-Ellison syndrome). The acid
hypersecretion caused by the excess gastrin acidifies the duodenum, which stimulates excessive secretin secretion. Secretin
has several roles such as 1) regulation pH of the duodenal content by inhibiting gastric acid secretion, 2) regulation of bicarbonate ion
secretion into the duodenum from the pancreas and biliary tract, 3) water homeostasis in the kidney, and 4) functions in the CNS, heart,
and cardiovascular system.

A functional neoplasm in the stomach antrum (choice A) is incorrect because gastrinomas most often occur in the pancreas,
probably derived from pluripotential neuroendocrine stem cells (APUD stem cells).
Atrophy of fundal gastric epithelium (choice B) is incorrect because gastrin causes hypertrophy of the parietal cells in the
epithelium of the fundus and corpus, thus helping increase basal gastric acid secretion.
Somatostatin secretion would be increased, not decreased (choice D), in this patient. Somatostatin is a part of the negative
feedback system that keeps acid production in check. Acid hypersecretion is sensed by D cells, which release somatostatin into
the surrounding mucosa. In a normal person, somatostatin inhibits acid production directly though actions on parietal cells, and indirectly
by inhibiting gastrin release from G cells and histamine release from ECL cells.
Watery diarrhea and hypokalemia (choice E) is seen with vasoactive intestinal peptide tumor of the pancreas (VIPoma).
Excretion of large amounts of potassium and bicarbonate in the stool causes hypokalemia. Although this can also be present with MEN I
syndrome, our patient has elevated levels of gastrin, which points toward a gastrinoma rather than a VIPoma. Note: Steatorrhea is
associated with gastrinoma, secondary to inhibition of pancreatic lipase due to low duodenal pH.
Updated on 03/29/16
This patient has pseudomembranous colitis, a diagnosis that must be considered in any patient presenting with diarrhea soon after
initiating antibiotics. Pseudomembranous enterocolitis is caused by the toxins produced by Clostridium difficile.Clostridium
difficile is a motile spore-forming gram-positive bacillus that is a part of the normal gastrointestinal flora. Systemic antibiotics
disrupt the normal GI flora, but C. difficile may survive by forming spores. The spores later germinate and the organism grows
rapidly due to lack of competition from other bacteria. Toxin A acts as a granulocyte attractant and toxin B is cytopathic.
Even if it is difficult to determine the exact antibiotic this patient is currently taking, the fact that she recently started therapy should
instantly make the physician think of antibiotic-associated diarrhea or pseudomembranous colitis. The oral antibiotic this
patient is currently taking is probably clindamycin, which is an antibiotic commonly used (in addition to tetracyclines) for the treatment
of moderate to severe acne. It has a mechanism of action and resistance similar to that of macrolides, and is generally used to treat
infections caused by anaerobic organisms and certain gram-positive organisms. Patients with pseudomembranous colitis develop fever
and abdominal pain. Culture is nondiagnostic because the organism is part of normal flora, which has overgrown.
Characteristic features of the disease include the formation of inflammatory, yellow-tan pseudomembranes in the colon. The diagnosis
is made by the C. difficile toxin assay. The initial treatment of choice is with metronidazole (an alternative is vancomycin).
Vancomycin does not cross the GI mucosa and so needs to be given orally, whereas metronidazole is effective both orally and
intravenously.
Adherence of organisms to the intestinal mucosa causing fat malabsorption (choice A) is themechanism of pathogenesis for Giardia
lamblia. G. lamblia causes a fatty diarrhea, with bloating and tender abdominal pain, but is not associated with antibiotic usage.
Induction of prostaglandin synthesis causing increased cAMP (choice C) is the mechanism of pathogenesis for several of the
nontyphoidal salmonellae, but these agents of diarrhea are not associated with antibiotic use.
Invasion of the colonic mucosa attracting a neutrophilic infiltrate (choice D) is the mechanism of pathogenesis for most of the
agents of inflammatory diarrhea, but C. difficile (a member of the normal flora) does not invade the bowel wall, but simply overgrows
when other normal flora organisms have been disturbed by treatment with antibiotics.
Molecular mimicry stimulating autoimmunity (choice E) is the proposed mechanism of pathogenesis for several autoimmune
arthritides and inflammatory bowel disease, but C. difficile does not promote autoimmune disease
he correct answer is A. This is a hyperplastic polyp. Hyperplastic polyp, by definition is a proliferation of glands without
atypia, whereas adenomas have dysplasia (atypia). Hyperplastic polyps comprise 90% of all colonic polyps and have no
malignant potential. The following chart describes the spectrum of polyps from hyperplastic polyps to villous adenomas.

Peutz-Jeghers polyps (choice B) are hamartomatous polyps, which have a low malignant potential. They tend to be larger and
have a complex branching pattern. Peutz-Jeghers syndrome can have hamartomatous polyps as well as adenomatous polyps, and is part
of the inherited adenomatous polyposis syndromes. These patients have increased risk for malignancy of the GI tract, liver, pancreas,
breast, and cervix. Colon carcinoma can arise from adenomatous poylps rather than hamartomatous polyps.

Tubular adenomas, tubulovillous adenomas, and villous adenomas (choices C, D, and E) are alltrue neoplastic polyps, which can
progress to dysplastic epithelium. The malignant potential of these polyps increases with size (greater than 2 cm). Villous adenomas
have a greater risk for malignant potential (over tubular adenoma) due to the flattened and larger morphology of these adenomas.
Note: Serrated adenomas are another type of colon polyp, which is a combination of hyperplastic polyp and a tubular adenoma.
Histologically, serrated adenomas (aka serrated polyps) have prominent elongated crypts with jagged, "saw-tooth" crypts, and cellular
atypia.
Updated on 03/29/16
Acute gastritis, characterized by patches of erythematous mucosa, sometimes with petechiae and/or ulceration, can be seen
as a complication of a variety of conditions, including uremia. Other causes are alcohol, aspirin, other NSAIDs, steroid use, smoking,
head trauma (Cushing ulcers), burns (Curling ulcers), and shock. Most causes of gastritis disrupt the gastric mucosal barriers. Overacidification, like that seen in Zollinger-Ellison syndrome (gastrinoma), also causes profound, acute gastritis. Bleeding sometimes occurs,
causing melena and guiaic positive stools.
Uremia is also associated with anemia, coagulopathy (dysfunctional platelets), pericarditis, and heart disease.
Hypertrophic gastritis (Menetrier disease; choice B) is an idiopathic condition characterized by markedly enlarged mucosal folds.
Lymphocytic gastritis (choice C) is thought to be a gastric manifestation of celiac sprue.
Chronic fundal (type A) gastritis, or atrophic gastritis, (choice D) is the type associated withpernicious anemia. Auto-immune
destruction of gastric mucosa, specifically parietal cells, which produce intrinsic factor, limits vitamin B12 absorption in the ileum. Loss of
parietal cells decreases acid secretion, a condition known as achlorhydria. Recall that intrinsic factor (IF) is required for B12 absorption.
B12 deficiency causes macrocytic anemia, hypersegmented neutrophils, and degeneration of nerve tracts in the spinal column. An autoantibody against IF or parietal cells may be present.
Chronic gastritis may cause intestinal metaplasia, a risk factor for adenocarcinoma. Types A and B gastritis are associated with increased
risk for gastric adenocarcinoma, as well as gastric B cell lymphoma.
Chronic antral (type B) gastritis (choice E) is associated with Helicobacter pylori infection.
Calcium bilirubinate gallstones (black pigmented stones) are derived from degradation of heme. They are seen in patients
with chronic hemolytic disorders, such as this patient's hereditary spherocytosis. Brown pigment gallstones, which are associated with
bile tract infections, are also comprised of calcium bilirubinate.
Hereditary spherocytosis is a condition caused by a membrane protein defect of red blood cells. The most common defect is in the
cytoskeletal protein ankyrin or spectrin, which causes spherocyte formation. See image below (arrows point to spherocytes). These
abnormal red cells are removed from the circulation in the spleen (extravascular hemolysis). Heme will subsequently be broken down into
unconjugated bilirubin. Treatment is splenectomy and cholecystectomy.
The high-pitched ("tinkly") bowel sounds heard over the abdomen are those of small intestinal obstruction. When coupled
with the distended abdomen, they specifically suggest jejunal or ileal small intestinal obstruction. Causes of jejunal and ileal
obstruction in adults include hernias, adhesions, tumors of the small intestine, foreign body, Meckel's diverticulum, Crohn
disease, Ascaris infection, midgut volvulus, and intussusception by tumor. Ascariasis is a common nematode (roundworm) infection
worldwide. Infection can occur from contaminated soil contact with hands or feet, or from ingestion of eggs. Eggs can hatch in the small
intestines. In additions to intestinal symptoms, patients can also have cough, dyspnea, wheezing, chest pain, and jaundice.
Duodenal ulcer (choice B) and pancreatic cancer (choice E) can cause duodenal obstruction. However, without a prior history of ulcers
or gastritis, or without a history of weight loss or smoking, these conditions are less likely.
Entamoeba histolytica (choice C) and Hirschsprung disease (choice D) affect the large bowel. Entamoeba can present with cramping
abdominal pain, watery or bloody stools, and weight loss. Hirschsprung disease can be either congenital or acquired (e.g., Chagas
disease).

Megaloblastic anemia with neuropathy suggests vitamin B12 (cobalamin) deficiency, which in this patient suggests pernicious
anemia. Neurologic symptoms are the result of subacute combined degeneration, characterized by demyelination and degeneration
of the dorsal and lateral white matter of the spinal cord. Symptoms include glove and stocking paresthesias (numbness and tingling),

decreased sensation, and gait disturbances. Patients will also have glossitis and macrocytic RBCs with hypersegmented neutrophils.
Pernicious anemia is associated with autoimmune chronic gastritis and seen in adults over age 30, with a peak age of 60.
In this condition, an autoimmune attack on gastric parietal cells or intrinsic factor leads to atrophic gastritis(chronic gastritis
type A) with deficient synthesis of the intrinsic factor (IF). Haptocorrin (R-protein) binds to vitamin B12 in the stomach and
protects vitamin B12 from the acidic environment. In the duodenum, pancreatic proteases cleave this complex and release vitamin B12,
where IF can bind to create the vitamin B12-IF complex. The complex is then absorbed in the ileum. Vitamin B12 is required for DNA
synthesis in blood cell precursors; deficiency produces megaloblastic anemia. Chronic atrophic gastritis predisposes an individual
to the development of gastric carcinoma.
Causes of vitamin B12 deficiency include:

Pernicious anemia: Autoimmune gastritis

Nutritional: Pure plant-based diet; diet lacking meats, diary, eggs

Surgery: Removal of stomach or ileum (source of IF or absorption of IF) or ileal bypass

Crohn disease: Inflammation of the ileum

Fish tapeworm Diphyllobothrium latum infection

Medications: Purine and pyrimidine antagonists

Blind loop syndrome: bacterial overgrowth

Vitamin B12 deficiency is associated with elevated levels of methylmalonic acid (serum and urine) and serum homocysteine.
Recall, methylmalonyl CoA is converted to succinyl CoA and homocysteine is converted to methionine. Without B12, these reactions
cannot proceed, leading to their accumulation. In contrast, folate deficiency will only have an increase homocysteine level. Note: due to
elevated levels of homocysteine, these patients have an increased risk for development of cardiovascular disease.
Predisposing factors for colon cancer (choice A) include familial polyposis syndromes, inflammatory bowel disease (ulcerative
colitis), isolated adenomatous polyps, and a diet high in animal fat.
Duodenal (choice B) and ileal (choice D) cancers are uncommon.
Predisposing factors for esophageal cancer (choice C) include chronic exposure to hot foods/liquids, tobacco smoking, Barrett
esophagus (associated with adenocarcinoma of the lower esophagus) and Plummer-Vinson syndrome (associated with iron deficiency
anemia, esophageal webs, difficulty swallowing, and squamous cell carcinoma of the upper esophagus and pharynx).

Duodenal biopsies reveals flattened villi, suggesting that the patient has celiac disease (celiac sprue), which is caused by an
allergic, immunologic, or toxic reaction to the gliadin component of gluten (from wheat and related grains). Serologic screening for antitissue transglutaminase IgA antibodies is sensitive and specific for celiac disease. Although tissue is present in the name of the
test, it is measured in the blood. Other serologic tests measure anti-gliadin (IgA or IgG) and anti-endomysial (IgA) antibodies.
Antigliadin IgG antibody level is useful to detect celiac disease in IgA deficient patients (occurs in 2-3% of celiac disease patients) as well
as for monitoring disease.
Villi amplify intestinal surface area, thereby increasing contact between digestive enzymes and ingested nutrients, and increasing net
epithelial absorptive capacity by increasing transporter availability. The stunting of villi that occurs in patients with celiac disease
impairs digestion and absorption, so they typically lose weight. Undigested or partially digested nutrients pass through the small
intestine to the colon, where they are acted on by bacteria to cause diarrhea and flatulence. The symptoms and pathologic changes
usually reverse with the complete removal of gliadin from the diet. Therapeutic failures are frequently due to non-compliance or
hidden wheat in the diet (wheat flour is present in a wide range of commercially-available food products).
Antibodies to cyclic citrullinated peptide (choice A), along with the presence of rheumatoid factor, are seen withrheumatoid
arthritis. Patients present with symmetric tender, swollen, warm joints of the hands and wrists. Other joints of the knees, ankles,
and elbows can also be involved. Subcutaneous rheumatoid nodules are present near the elbows. There is no direct connection
between rheumatoid arthritis and celiac disease.
Helicobacter pylori infections (choice B) are responsible for the majority of gastric and duodenal ulcers seen in patients with peptic
ulcer disease. Upper endoscopy failed to reveal such a lesion in the gastric antrum or the proximal duodenum. Villous atrophy is not
related to Helicobacter infection.
Anti-mitochondrial antibodies (choice C) are found in the majority of patients with primary biliary cirrhosis (PBC). This autoimmune
condition more commonly affects older females (age 40-60 years), primarily involves theintrahepatic biliary tracts, and
causes lymphocytic and granulomatous destruction of bile ducts. There is no association with celiac disease. Patients present with
fatigue, pruritis, and right upper quadrant discomfort. High lipid and cholesterol levels are noted, with increased risk for cardiovascular
disease. Serum alkaline phosphatase would also be elevated. Patients may also present with fat malabsorption and steatorrhea,

similar to our patient, from lack of bile secretion into the GI tract. However, patients with celiac disease have a more broad nutritional
deficiency and marked weight loss.
Anti-smooth muscle antibodies (choice D) are seen in autoimmune hepatitis. Females are more affected than males. Patients can
also have elevated anti-nuclear antibodies (ANA) and present with fatigue and jaundice. There is no direct connection of
autoimmune hepatitis and celiac disease. NOTE: Although anti-mitochondrial antibodies are pathognomonic for primary biliary cirrhosis,
anti-smooth muscle antibodies can also be present in 50% of PBC patient
The morphologic features show disruption of the normal hepatic lobules with lymphocytic infiltrate. Apoptosis is not clearly seen at this
magnification, but affected cells would be present in the center or periphery of the infiltrate. This patient has either a viral (hepatitis B or
C) or autoimmune hepatitis, which is associated with apoptosis. Further serologic studies are required to determine the definitive
diagnosis.
The features of apoptosis include: cell shrinkage, chromatin condensation, bright eosinophilic cytoplasm, and cytoplasmic membrane
bleb formation (image below; arrows). Apoptosis is a form of programmed cell death, which eliminates unwanted or damaged cells,
and is usually not associated with necrosis. It results from caspase enzyme initiation. There are two distinct pathways: the intrinsic
(mitochondrial) pathway and the extrinsic (death receptor; Fas or TNF receptor) pathway.

Laboratory of Experimental Pathology, Division of Intramural Research, NIEHS (NIH)

Apoptosis can be seen with:

Physiologic conditions
o

Embryogenesis

Hormone withdrawal: endometrial cells, lactational breast, prostate after castration

Cell proliferation: bone marrow, intestinal epithelial cells, thymus, lymph node

Elimination of potentially harmful lymphocytes

Death of neutrophils, lymphocytes after inflammation

Pathologic conditions
o

DNA damage: radiation, hypoxia, drugs

Accumulation of misfolded proteins (CNS degenerative disorders)

Cancer cells

Viral infections

Transplant cellular rejection and graft versus host disease

Autophagy (choice B) is a process in which a cell eats its own content. The mechanism is distinct from apoptosis and necrosis. When
exposed to cellular stresses, such as nutrient deprivation, the process is activated. An autophagosome forms, fusion with lysosome
occurs, cellular contents are degraded, then metabolites are recycled. Dysregulation of autophagy can occur in cancer (enables
cancer cell growth), neurodegenerative conditions (Alzheimer disease, Huntington disease), and inflammatory bowel disease (association
with autophagy-related genes).
Coagulative necrosis (choice C) is a form of necrosis in which the cellular architecture is preserved (ghost cells) for days to
weeks. Ischemia leads to coagulative necrosis. Morphologic features include increased cytoplasm eosinophilia, cell swelling, nuclear
changes (karyolysis, pyknosis, and karyorrhexis), and membrane blebs. Our patient does not have any cause for hepatic infarction that
would lead to coagulative necrosis.
Liquefactive necrosis (choice D) is associated with enzymatic digestion of cells. It is seen in CNS infarction, acute pancreatitis, and
abscess. Our patient does not have any cause for conditions that would lead to liquefactive necrosis.
Steatosis (choice D) is the intracellular accumulation of triglycerides. Histologically, cells have preserved nuclei, which can
be displaced to one side by clear cytoplasmic vacuoles. Steatosis may be seen with exposure to toxins, obesity, alcoholism, Reyes
syndrome, malnutrition, and non-alcoholic fatty liver disease.
Updated on 02/09/16

The tumor is a hepatocellular carcinoma (HCC), which usually develops in the setting of cirrhosis due to a variety of damaging agents,
including hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, alcohol abuse, and hemochromatosis. The mechanism of
oncogenesis in hepatitis B infections is thought to be through integration of the viral genome into the chromosomes, and integrated
viral DNA is found in all transformed cells.
In the United States, alcoholic hepatitis and HCV infection are both more common than HBV infection. Therefore, in the U.S., HCC is more
likely to be associated with either alcohol abuse or HCV. This is also most likely due to high rates of vaccination against HBV in the U.S.
Capture of cellular oncogenes (choice A) is believed to have occurred in the oncogenic retroviruses. Human T-cell leukemia virus
(HTLV-1 and -2), which causes adult T-cell leukemia/lymphoma, is one such virus. Since retroviruses incorporate their genomes
into the chromosomes of the cells they infect, accidental capture of cellular oncogenes is believed to have resulted in the viruses'
possession of homologs of cellular growth genes. It is important to also note that HIV is a retrovirus with increased malignancy risk (e.g.,
Kaposi sarcoma, B cell lymphoma).
Down-regulation of class I MHC on the tumor cells (choice B) occurs with many viral infections, such ascytomegalovirus, but in these
particular cases, the natural killer (NK) cell activity would compensate for any decrease in cytotoxic T lymphocyte (CTL) killing. This
is not a mechanism of tumorigenesis.
Inactivation of tumor suppressor genes (choice C) is the mechanism of oncogenesis for human papillomavirus (HPV)when it causes
oral, cervical, and genital-urinary squamous cell carcinoma. HPV induces overexpression of E6 and E7 proteins, which act to overcome
the activity of cell-cycle inhibition. E6 binds to p53 and E7 binds to Rb, key proteins in cell cycle regulation, and induces degradation of
these proteins.
Translocation involving an oncogene (choice E) is the mechanism of oncogenesis for Burkitt lymphoma, where it translocates the cmyc oncogene near the active immunoglobulin heavy chain genes in infected cells. Other tumors involving translocation involving
oncogenes includes follicular lymphoma.
Updated on 10/02/15
. In this case, the vitamin D deficiency is due to fat malabsorption, secondary to ileal resection. If more than 100 cm of the ileum is
removed, primary bile acid production by the liver cannot keep up with bile salt loss in the stool. The total bile salt pool decreases,
and fat absorption is decreased, including the fat-soluble vitamins. Serum calcium is low, secondary to the decreased
dietary absorption. Serum parathyroid hormone (PTH) increases in response to the low calcium. Serum phosphate is low because
of decreased dietary absorption and increased renal excretion (caused by the increased PTH).
Vitamin D deficiency produces osteomalacia, or demineralization of the bones. Vague complaints of weakness and bone pain may be
present; however, the clinical manifestations often go unnoticed. Radiographic changes in the bones affected by osteomalacia result in
pseudofractures. These pseudofractures are often in the inner aspects of the femur and the pubic rami and the outer edges of the
scapulas, upper fibula, and metatarsals. Pseudofractures are radiolucent bands that are perpendicular to the bone surface. They may
occur because of pulsations of major arteries that cross the bone.

Osteoporosis (choice A) is characterized by loss of bone massboth matrix and mineral. It is usually asymptomatic, and serum
levels of calcium, phosphate, and PTH are within the normal range. The first hint of bone loss comes from a fracture in the wrist,
hip, or vertebra. Dual-energy radiography or other similar techniques can be used to quantify the degree of bone loss directly.
In Paget disease (choice B), bone mineral turnover is increased compared with normal. The cause is unknown but may be
aparamyxovirus that infects osteoclast cells. Both osteoblast and osteoclast activity is increased in focal areas of the bone. The
disease is often asymptomatic; however, when there is a complaint, it is often bone pain over the lesions. Laboratory findings
include increased serum alkaline phosphatase, but serum calcium and PTH levels are usually normal.
In primary hypoparathyroidism (choice C), serum calcium and serum PTH are decreased, but serum phosphate is increased.
Serum phosphate is increased because urinary excretion is diminished, secondary to the decrease in PTH.
In renal failure (choice D), an increase in serum phosphate, secondary to decreased urinary excretion, is the primary
manifestation.Serum calcium is decreased because the hyperphosphatemia drives the equilibrium between calcium and phosphate
toward hydroxyapatite crystals. This produces an increase in PTH secretion with subsequent bone demineralization (renal
osteodystrophy). Renal failure The observation that the diarrhea resolved when nutrition was provided via the intravenous route rather
than orally implies that the diarrhea could be attributed to gastrointestinal malabsorption of an ingested nutrient. Unabsorbed solutes
present in the GI tract draw water into the intestine, producing an osmotic diarrhea. The low pH of the stools points tolactose
malabsorption in the small intestine as the source of the osmotic diarrhea. Undigested lactose passes rapidly from the small intestine to
the colon, where bacteria act on it to form acidic end products (e.g. acetate and propionate) and hydrogen gas.
Lactase deficiency occurs in several forms. Congenital deficiencies (due to either complete absence of lactase or production of a
defective lactase protein) present in infancy and are inherited as rare autosomal recessive traits. This infant's history suggests
congenital deficiency. Much more commonly, lactase deficiency can present either after weaning or in adults, and is related to
polymorphism in the lactase genetics that leads to decreased expression of the lactase protein as a person ages, and presumably no
longer requires lactose-containing milk in the diet. This form of lactase deficiency is more prevalent in African, Asian (E. Asian, Indian,
Native American), and, to a lesser degree, certain Mediterranean populations (Southern French, Italian) groups. Lactase deficiency is also
sometimes seen as an acquired disorder secondary to intestinal diseases such as celiac disease, Crohn disease, and giardiasis.
Dysfunctional lipid absorption (choice A) is characterized by steatorrhea. Bacteria acting on undigested lipids produce bulky and
greasy stools.
Hirschsprung disease (choice B), the congenital absence of enteric neurons in the muscle wall of the distal colon, is characterized
by constipation due to the lack of peristaltic activity in the affected region of the GI tract.
Secretory diarrhea (choice E), resulting from active electrolyte transport into the lumen of the GI tract, is most often caused
byinfectious agents (choice C). Hormone-secreting tumors can also provoke secretory diarrhea. Secretory diarrhea does not
resolve by fasting or parenteral nutrition.
is unlikely in this patient with normal BUN and cr
This child's history strongly suggests gluten-sensitive enteropathy (celiac disease), the pathologic hallmark of which is
the flattening of small intestinal villi. The condition is due to intolerance to gluten, which is found primarily in wheat and rye
products. Villi and the microvilli that they support together create an small intestinal surface area of approximately 200 m 2. Villous
atrophy reduces this surface area drastically and thereby reduces the capacity to digest and absorb nutrients, explaining the patients
fatigue and weight loss. Ingested food passes through to the colon only partially digested, producing stools that are typically bulky and
foul-smelling. Celiac disease may present in childhood or in adulthood. Treatment includes complete removal of gluten from the diet.
Symptoms can completely remit with dietary modifications.
These patients are at increased risk for developing dermatitis herpetiformis. Dermatitis herpetiformis is an intensely itchy skin
eruption on the elbows, knees, scalp, buttocks, and back. Celiac disease is also associated with intestinal lymphoma and breast cancer,
but patients do not have an increased risk of developing Crohn disease or ulcerative colitis.
Both ulcerative colitis (choice E) and Crohn disease (choice B) may present with episodes of bloody diarrhea. Both conditions often
include crampy lower abdominal pain and fever. They are, however, associated with different extraintestinal manifestations.
Inflammatory bowel diseases, particularly ulcerative colitis, carry an increased risk for colon adenocarcinoma (choice A). Crohn disease
can be associated with jejunal strictures (choice D).
Updated on 11/07/15
he correct answer is D. Entamoeba histolytica is the usual cause of intestinal amebiasis, and has the microscopic features described
in the question stem. A particularly helpful (but not always present) feature of this organism is the presence of ingested red blood
cellswithin the amoebae. These amoebae are invasive and cause flask-shaped ulceration of the intestinal mucosa and submucosa,
with a particular propensity for involving the cecum and ascending colon. The disease manifestations range from asymptomatic
carriers to severe, purging dysentery. Patients may present with blood and pus in the stool. The liver may develop destructive
amoebic liver abscesses that tend to become secondarily (and potentially life-threateningly) infected by bacteria.
The following table reviews the three most common diarrhea causing amoebae:

Acanthamoeba (choice A) is a free-living amoeba that can cause amoebic meningocephalitis and does not infect the GI tract. People
who swim in infested waters can inhale the amoeba into their nasal cavity, which can invade through the cribriform plate. Acanthamoeba
can also enter the lower respiratory tract or broken skin of immunocompromised hosts and travel hematogenously to the brain.
Balantidium coli (choice B) is a large ciliated intestinal parasite that can occasionally cause colonic disease resembling that caused
byEntamoeba histolytica. However, it is not as common.
Cryptosporidium parvum (choice C) is a protozoan that causes diarrhea similar to Entamoeba histolytica. Cryptosporidium generally
affects immune compromised hosts (e.g., AIDS patients). Cysts are usually present on the epithelial surface and are not associated with
ulceration. Treatment involves supportive care, antimicrobial agents, and restoring immune function.
Giardia lamblia (choice E) is a small intestinal protozoan with a distinctive pear-shaped morphology that appears to have a "face." They
usually infect the small intestines, rather than the large intestines, and do not cause ulcerations. Symptoms include diarrhea and
bloating.
Updated on 06/26/15

The symptoms described here are collectively called "dumping syndrome." Because part of the stomach is bypassed in the surgery,
an ingested meal will be delivered to the small intestine more quickly than normal. The large increase in tonicity in the small intestine
causes an osmotic fluid shift from the extracellular fluid (plasma) into the lumen of the gut. The increased distention of the
small intestine increases motility through reflex mechanisms and causes diarrhea. The blood volume contraction and
concomitant release of vasoactive substances such as bradykinin and/or vasoactive intestinal peptide can create hypotension and reflex
tachycardia.
Patients should be instructed to eat smaller, more frequent meals that are rich in protein to reduce the osmotic and/or
carbohydrate load that is delivered to the small intestine. Furthermore, since fats are the slowest to be absorbed, a diet that is
higher in fat will also reduce the problem of rapid absorption, although a high-protein diet is generally recommended for nutritional

reasons. Complex carbohydrates are less likely to cause dumping syndrome than simple sugars. Fruit juices are very likely to
cause this syndrome. Consumption of high volumes of fluids with meals should also be avoided.
The correct answer is A. This neonate has meconium ileus, which is the first manifestation of cystic fibrosis. Meconium plugs
appear on contrast enema. The air-fluid levels in the right lower quadrant are signs of obstruction proximal to the ileus. Meconium ileus
can cause gut perforation with peritonitis and intraperitoneal calcifications that may be visible on plain film. Meconium ileus may be
complicated by formation of fistulas to the bladder or vagina, which must be treated surgically. Medical treatments for uncomplicated
meconium ileus include use of enemas, mucolytic agents, and pancreatic enzymes.
Diaphragmatic hernia (choice B) typically presents with acute respiratory distress secondary to failure of lung expansion (particularly
once the loops of bowel fill with swallowed air) in the first minutes to hours of life.
Esophageal atresia (choice C) usually presents in the first days of life with regurgitation of unaltered food; bile staining of the
vomitus would not be seen.
Hirschsprung disease (choice D) is a cause of congenital constipation related to absence of ganglion cells in a segment of bowel.
The aganglionic bowel segment is narrowed because the lack of peristalsis keeps stool from moving into the segment. The distal rectum
is always involved, and the lesion may extend proximally as far as the small intestine. The bowel proximal to the aganglionic
segment is usually dilated. Hirschsprung disease is also seen with Down syndrome. Because no areas of constriction were seen,
Hirschsprung disease is unlikely in this patient. In addition, a rectal exam after progressive dilation may alleviate the obstruction. Feces
can be ejected violently after rectal examination. This is not diagnostic, but it points toward Hirschsprung disease.
Hypertrophic pyloric stenosis (choice E) causes non-bilious projectile vomiting that typically begins in the 4th to 6th week of life.
Meckel diverticulum (choice F) can form due to the persistence of the vitelline (omphalomesenteric) duct, which connects the
developing gut to the yolk sac. They are classically located in the distal ileum within 60-100 cm (2 feet) of the ileocecal valve, and may
contain ectopic pancreatic tissue or gastric mucosa. The classic presentation of Meckel diverticulum in children less than 2 is with
painless rectal bleeding secondary to formation of an ulcer caused by acid secretion of ectopic gastric mucosa. Neonatal presentation of
Meckel diverticulum has been described (and may even resemble meconium ileus clinically and radiologically), but is very rare

The patient's disease is primary biliary cirrhosis (PBC), which is an autoimmune disease characterized by granulomatous
inflammation of the small and medium biliary ducts and progression to fibrosis and cirrhosis. PBC is more common in women,
and typically is characterized by increased conjugated bilirubin, alkaline phosphatase, gamma-glutamyl transferase, and IgM.
The most helpful clue in the question stem is theantimitochondrial antibody, which is present in over 90% of these patients. The
course is usually slowly progressive over 5 to 25 years. Patients with advanced disease tend to develop
profound hypercholesterolemia andxanthomas. Serum cholesterol is elevated due to impaired cholesterol metabolic degradation and
excretion. Cholesterol is normally excreted in bile, and with reduced bile formation and excretion, cholesterol is retained within the cell
and may be redistributed from tissues into plasma. Much of plasma cholesterol is in the form of lipoprotein-X and HDL.
Primary sclerosing cholangitis is in the differential for this patient, given the presentation, but primary sclerosing cholangitis is primarily a
disease of men, often associated with inflammatory bowel disease, and shows p-ANCA in the serum, rather than antimitochondrial
antibodies.
Serum alanine aminotransferase (choice A) and serum aspartate aminotransferase may be elevated, rather than decreased. These
values reflect damage to hepatocytes and tend to be less specific for the diagnosis of primary biliary cirrhosis.
Patients are sometimes diagnosed when routine blood tests demonstrate an elevated alkaline phosphatase (choice B).
Serum bilirubin (choice C) is mildly increased, rather than decreased in PBC, which reflects cholestasis. Markedly elevated levels
are seen in late-stage disease, and suggests that the patient may be close to needing a liver transplant. The hepatocyte can upregulate
MRP transporters, which can mobilize conjugated bilirubin and bile acids out of the hepatocytes and into the circulation.
Serum albumin levels (choice D) are often decreased as the disease progresses, due to decreased synthetic capacity by the liver.
Updated on 04/24/16

acute erosive gastritis include NSAID use, severe burn (Curling ulcer), shock, stress, heavy alcohol use, increased
intracranial pressure (Cushing ulcer), and chemotherapy.

Chronic gastritis can be further classified as a chronic autoimmune (type A) gastritis or chronic H. pyloriassociated (type B)
gastritis.

This patient has autoimmune gastritis (type A; "A" for "Autoimmune"), which is characterized by atrophy and chronic inflammation of
mucosa of the fundus and body of the stomach. This form of gastritis is due to autoantibodies against either the parietal cells
or intrinsic factor (IF). These autoantibodies block binding of vitamin B12 (cobalamin) to IF ("blocking" antibodies), thus preventing
absorption of vitamin B12. Antibodies directed against parietal cells would also cause achlorhydria. There is increased risk for
development of gastric lymphoma or carcinoma.
Vitamin B12 is required for DNA synthesis. A deficiency causes a dyssynchronous maturation in which the nucleus of hematopoietic
cells becomes larger than the cytoplasm. The resultant picture is pernicious anemia: megaloblastic anemia, with abnormally large
(macrocytic) erythrocytes and hypersegmented neutrophils. Laboratory findings of megaloblastic anemia include increased mean
corpuscular volume (MCV), elevated serum or urine methlymalonic acid, elevated homocysteine levels, and decreased vitamin B12
levels.
Neurologic symptoms (paresthesia, decreased vibration and position sensation, ataxia, lack of coordination) may be present as well,
since vitamin B12 is needed for myelin production in the central nervous system (severe combined degeneration of the spinal
cord). Patients with autoimmune gastritis/pernicious anemia can also develop Hashimoto thyroiditis and gastric carcinoma.
Chronic alcohol use (choice B) is associated with an acute erosive gastritis. It erodes the gastric mucosa, causingseveral small
mucosal ulcerations. These patients may also not have good nutrition and can have folate and vitamin B12 deficiency to cause
megaloblastic anemia. In addition, chronic alcohol can affect bone marrow hematopoiesis and contribute to a non-megaloblastic form of
macrocytic anemia. However, the gastric atrophy and lymphocytic infiltrate seen in this patient do not support megaloblastic anemia
from chronic alcohol use.
Crohn disease (choice C) can involve any part of the GI tract, but more commonly the small intestine and colon. Inflammation of the
ileum and/or surgical resection can contribute to vitamin B12 deficiency. Microscopically, there would be transmural
lymphoplasmacytic inflammation with presence of granulomas. This patient is less likely to have Crohn disease since the vignette
focuses mainly on a gastric issue without mention of small intestine involvement.
Fish tapeworm infestation (choice D) implies infection with Diphyllobothrium latum. This tapeworm parasite is acquired by ingestion of
undercooked fish. It competes for the host vitamin B12 in the intestinal tract. There is no involvement of the stomach with this type of
infection. Leukocytosis with eosinophilia may also be present in addition to megaloblastic anemia.
H. pylori infection (choice E) is an important pathogenic factor in chronic gastritis (type B; "B" for "Bacteria"), affecting
the antral mucosa in isolation or in association with involvement of the body of the stomach. Chronic inflammation with
lymphocytic infiltration of the mucosa is found on biopsy, and H. pylori can be demonstrated by appropriate silver staining. H. pyloriassociated chronic gastritis is usually asymptomatic or manifests with mild and nonspecific upper abdominal discomfort. There is
a strong association between H. pylori infection and peptic ulcer disease. Treatment is with antibiotics and proton pump
inhibitors. If untreated, H. pylori also plays an etiologic role in the development of gastric lymphoma or carcinoma
The portion of the bowel that has infarcted is the middle third of the transverse colon. This area is supplied by the middle colic artery,
a branch of the superior mesenteric artery (see figure). This portion of the bowel is vulnerable to infarction because the collateral
circulation linking the distributions of the superior and inferior mesenteric arteries (by way of the middle colic and left colic arteries) is
poorly developed. In theory, an embolus to this area could arise from either the superior mesenteric artery or the middle colic artery.
However, the superior mesenteric artery is the much more likely source because it is a larger vessel with higher pressures and
turbulence, and is more likely to develop the severe atherosclerosis that can give rise to emboli.

The appendicular artery (choice A) is a small artery that supplies the appendix; it is a branch of the ileocolic artery, a branch of the
superior mesenteric artery. It is not likely to develop atherosclerosis or thrombosis that might give rise to emboli and does not supply the
transverse colon.
The celiac artery (choice B) supplies the stomach, liver, spleen, and proximal duodenum.
The inferior mesenteric artery (choice C) can also be a source of emboli that can cause bowel infarction, but the involved bowel would
be distal to the illustrated site and could involve the splenic flexure and descending colon.
The jejunal arteries (choice D) are small vessels that arise from the superior mesenteric artery and feed the jejunum; an embolus in
these vessels might infarct the jejunum, although this happens only infrequently because of the good collateral blood supply to this area.
he correct answer is B. Most pancreatic adenocarcinomas arise in the head of the pancreas. As the tumor grows, most tumors cause
epigastric pain. Note the dilatation of the common bile duct (shown by the single arrow). Obstruction of the common bile duct leads
to obstructive jaundice, characterized by elevated direct (conjugated) bilirubin. Patients may also present with migratory
thrombophlebitis and/or deep vein thromboses (Trousseau syndrome) due to hypercoagulable state.
Alkaline phosphatase can be elevated due to bile duct damage related to biliary duct occlusion. Painless distention of the
gallbladder (Courvoisier sign) is present on physical examination in about 50% of cases. CA-19-9 is the most specific and sensitive
serum marker for pancreatic cancer. Carcinoembryonic antigen (CEA) may also be elevated, but is nonspecific. In practice, these markers
are more useful in evaluation and monitoring of patients with known or suspected pancreatic cancer than they are in initial screening for
pancreatic cancer.
Cancer cachexia (choice A) is a late manifestation of disseminated neoplastic disease. Cachexia is also seen with AIDS, tuberculosis,
COPD, and multiple sclerosis. It is defined as wasting of adipose and skeletal muscle. Cachexia ismediated by certain
cytokines (e.g., TNF-alpha, IL-6).
Hyperglycemia (choice C) and polyuria (choice D), in addition to polydipsia and polyphagia, suggest glucose intolerance or frank
diabetes mellitus due to extensive destruction of the pancreatic islets, with resultant diabetes mellitus. This complication manifests
only after the destruction of at least 80-90% of pancreatic islets has taken place. Thus, a cancer located in the head of the pancreas is
very unlikely to manifest with secondary diabetes mellitus.

A pulsating epigastric mass (choice E) would suggest an abdominal aortic aneurysm (AAA), which should be considered as part of
the differential. Patients with AAA are usually asymptomatic until the aneurysm expands or ruptures, which can then present
with abdominal pain that radiates to the back, flanks and groin. It can also cause early satiety, nausea, and vomiting and/or
urinary symptoms (when compression is present). Patients with pancreatic cancer can present with a palpable abdominal mass, but it is
not the most common presentation. There are many things that can cause a pulsatile upper abdominal masses (e.g., lymphomas, gastric
cancer, hepatocellular carcinoma, liver hemangiomas). When dealing with non-specific signs and symptoms like epigastric pain,
abdominal masses, weight loss, etc., it is always very important to have a high degree of suspicion combined with a very careful history
taking, clinical examination, and appropriate imaging choices in order to establish the diagnosis.
The results of the endoscopic retrograde cholangiopancreatography indicate the presence of an obstruction in the common bile duct; this
would lead to an obstructive (cholestatic) jaundice. The ability of the liver to take up, conjugate, and secrete bilirubin is not impaired.
With cholestasis, the conjugated bilirubin in the hepatocyte would be transported back into the sinusoidal circulation (see figure),
producing a conjugated hyperbilirubinemia (not unconjugated hyperbilirubinemia, choice E). Conjugated bilirubin is watersoluble, can be filtered by the kidney, and appear in the urine. Thus, excessive filtration of conjugated bilirubin causes increased
urine bilirubin and produces a darkening of the urine (tea-colored).

Excessive hemolysis (choice A) produces an unconjugated hyperbilirubinemia because the ability of the liver to take up the
increased bilirubin from heme metabolism is exceeded. Hemolysis can be associated with pigmented (calcium bilirubinate)
gallstones, but the gallstones in this case were described to be composed of cholesterol.
An obstruction of the common bile duct would prevent the delivery of bile to the duodenum. As a consequence, the stool would be pale
rather than having increased pigmentation (choice B).
Urinary urobilinogen is a reflection of circulating urobilinogen. Urobilinogen enters the blood as part of the enterohepatic
circulation. Bilirubin secreted in the bile is ordinarily metabolized by gut bacteria to urobilinogen.Most urobilinogen remains in
the gut and, after further metabolism, provides the pigmentation to the stool. Some of the urobilinogen is absorbed by the ileum and
enters the enterohepatic circulation. Some of this absorbed urobilinogen ends up in the urine. With an obstruction of the common bile
duct, less urobilinogen reaches the small intestine, which means less enters the hepatic portal vein, resulting in
decreased urinary urobilinogen (not increased, choice D).

"ground-glass" hepatocytes (finely granular eosinophilic cytoplasm). The chronic active

hepatitis diagnosis is characterized bychronic inflammation with continuing necrosis
of hepatocytes surrounding the portal tract (AKA limiting plate)and extending into
the lobule with individual hepatocyte destruction (piecemeal necrosis). The
photomicrograph below shows chronic inflammatory cells at the top with many ground
glass hepatocytes in the lower half of the picture.

Acute hepatitis (choice A) is a term that is used with any acute inflammation of the liver. It may be induced by drugs, alcohol, or
viruses. The presenting symptoms include fever, loss of appetite, nausea, vomiting, jaundice, tender hepatomegaly, and
elevated liver enzymes. Histologically, the liver shows lymphocytic infiltrates and ballooning degeneration of hepatocytes.
Carrier state (choice B) is usually asymptomatic. This patient is already symptomatic and the liver histology is already abnormal.
Chronic persistent hepatitis (choice D), also called minimal chronic hepatitis, is a disease state with minimal symptoms and mildly
elevated enzymes. Inflammation is contained within the portal tracts and there is no lobular extension and no limiting plate activity
or piecemeal necrosis.
Cirrhosis (choice E) is the end stage of liver disease. The signs are portal hypertension and ascites. The liver shows bridging
fibrosis, not just periportal fibrosis

RESPIRATORY

This patient is having an acute asthma attack. In an asthmatic attack of

this severity, theFEV1, FVC, and the FEV1/FVC ratio will be
decreased; but the total lung capacity TLC will be increased due to
air-trapping and hyperinflation. As a practical matter, since the FEV1,
FVC, and lung volumes may be so difficult to measure in an acutely ill,
distressed patient, you also need to familiarize yourself with another
pulmonary function test parameter, peak expiratory flow rate (PEFR). The
PEFR can be determined from a hand-held device; can be performed even
by acutely ill patients; and can be performed by the patients themselves,
outside of the hospital, so they can accurately report their status and
trends when they speak with a healthcare provider.
Asthma is an obstructive lung disease primarily affecting air
movement out of the lungs (exhalation).The bronchoconstriction of
asthma results from inflammatory abnormalities of the airways and,
most importantly, frombronchospasm (bronchial smooth muscle

spasm). Moreover, asthma is characterized byairway hyperreactivity.This means that when an asthmatic patient is
challenged with an irritating stimulus (such as cold air, exercise,
cigarette smoke, or various allergens), bronchospasm will
develop earlier and in a more pronounced manner then for a nonasthmatic patient similarly challenged.Airway hyper-reactivity is
fundamental to asthma, and we cannot emphasize this concept
strongly enough! The patient in this case scenario clearly has a well
established diagnosis of asthma, but when a patient presents with very
mild and/or atypical symptoms, the technique ofbronchial provocation
testing may be utilized in the pulmonary function lab to make the
diagnosis. In this context, patients with asthma will demonstrate hyperreactivity, with more significant reductions in airflow (due to
bronchospasm) when challenged with noxious stimuli.
Regarding irritating stimuli, there are some that are relatively universal to
virtually all asthmatic patients (dust, cold air, cigarette smoke) and others
(allergens, exercise) that are more selective. It is worth knowing that cold
air causes the release histamine from mast cells and the release
of other biochemical mediators (e.g., certain leukotrienes), which
result in airway inflammation and bronchospasm. Therefore, it
should not be surprising that cold air-induced asthma can be managed
clinically by instructing the patient to take an antihistamine medication
and/or a bronchodilator several minutes going out into the cold air.
The patient in this case scenario probably has exercise-induced asthma,
since he developed his attack while playing soccer.Exercise-induced
asthma shares a common thread with cold air-induced asthma. It
is most likely caused by hyperventilating individuals with
increased minute ventilation--having larger volumes of air not
properly warmed and humidified by the upper airway passage-instead hitting the hyper-reactive lower bronchial airways and
causing bronchospasm. If you understand this concept for exerciseinduced asthma, you will also appreciate why it is more difficult to
manage skiers (who routinely perform in very cold, dry weather) than
swimmers (who routinely perform in a warmer, more humid environment).
However, prophylactic medications are, once again, very effective. There
have even been a number of world-class Olympic medal winning-athletes
in recent years who have dealt with and overcome exercise-induced
asthma.
Another key teaching point from this case involves the physical
examination for patients with acute asthma. Most patients with any
type of exacerbated asthma can be expected to have a prolonged
expiratory phase of respiration with lots of audible wheezes and
rhonchi.However, at the same time,it is essential for you to make
certain that the inspiratory phase of respiration, air entry, is at
least adequate.For the most severe episodes or in asthmatics
who are developing respiratory muscle fatigue, breath soundsboth inspiratory and expiratory will be diminished; adventitious
sound such as rhonchi and wheezes will diminish; and, in the

extreme, the patient may develop a so-called silent chest, one

of the most ominous findings that one can encounter in the
physical examination of an asthmatic, and often requiring the
immediate use of assisted ventilation.
Finally, we must also discuss the highly instructive blood gas data that is
referenced for this patient in the case scenario. Despite receiving
supplemental oxygen and despite being tachypneic, with an undoubtedly
large minute ventilation, he continues to be hypoxemic, and has a
relatively normal PaCO /pH. The hypoxemia results from the
ventilation/perfusion mismatch and widened A-a (alveolar-arterial)
gradient that is being caused by his asthma. His inability to maintain
respiratory alkalosis with a decreased PaCO and increased pH is alarming,
because it probably reflects the severity of his asthma attack and/or the
onset of respiratory muscle fatigue.
2

Over the years, some pulmonary physicians have utilized a staging

classification for arterial blood gas data in asthma

Stage 0: normal ABG data

Stage I: V/Q mismatch and widened A-a gradient for oxygen, but
patient is able to hyperventilate and to fully compensate, so
PaO normal/PaCO decreased/pH increased
2

Stage II: worsening of V/Q mismatch, but patient still able to

partially compensate, so PaO decreased/PaCO decreased/pH
increased
2

Stage III (patient in our scenario): compensation lost and now

developing fatigue, so significant hypoxemia/normalizing PaCO /and
normalizing pH
2

Stage IV: Acute respiratory failure, A MEDICAL EMERGENCY with

low PaO despite supplemental oxygen/ hypercapnia/ and low pH
acute respiratory acidosis
2

Updated on 09/14/15
ReKaps

Asthma is an obstructive lung disease that primarily affects

exhalation.

Pulmonary function tests show a typical obstructive pattern,

characterized by low FVC, FEV /FVC, FEV , and PEF (indicating an
exhalation problem).
1

The difficulty exhaling creates an "air-trapping environment"

represented by the increase of the parameters that include a
reserve volume: TLC, RV, and FRC.

Page References

MedEssentials (4th Ed.): pp. 293, 294

First Aid (2016): pp. 618.1, 619.2
First Aid (2015): pp. 610.1, 611.2
First Aid (2014): pp. 604.1, 607.2
First Aid (2013): pp. 554.1, 556.2
Pathoma (2015): pp. 91.1
Pathoma (2014): pp. 91.1
Pathoma (2013): pp. 91.1
Choice A: 3% chose this answer.
Choice B: 3% chose this answer.
Choice C: 9% chose this answer.
Choice D: 65% chose this answer.
Choice E: 20% chose this answer.
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A 23-year-old man comes to the emergency department because of sudden-onset shortness of breath and chest pain. The chest pain is retro-sternal and
left-sided, and is exacerbated by deep breathing and by cough. He has a history of asthma and uses albuterol only when needed. He is in moderate distress,
with a temperature of 98F (36.7C) and respiratory rate of 28/min. Physical examination shows normal breath sounds on the right and decreased breath
sounds on the left. Percussion of the left chest shows hyper-resonance. Arterial blood gas on room air shows:
PO

78 mm Hg
CO

25 mm Hg
pH
7.52

Which of the following is most likely to be seen on chest x-ray?

A. An infiltrate in the left lower lobe

B. A radiolucency along the left chest wall

C. A wedge-shaped opacity in the left lateral lung field

D. Fluid along the left costophrenic angle

E. Hyperinflation of both lung fields

aOL452

Explanation & ReKaps

The correct answer is B. This patient has suffered a spontaneous

pneumothoraxan accumulation of air within the pleural space
that often results in collapse of the lung. Pneumothoraces are quite
common. They are often caused by trauma but may also be secondary to
other lung pathology (i.e., tuberculosis, malignancy, emphysema,
pulmonary infarction, etc.). In addition, they may occasionally occur as
iatrogenic complications of medical procedures such as subclavian central
venous line insertion or thoracentesis.
In this case, a pneumothorax has arisen spontaneously, most likely from
rupture of a small bleb (bulla) in the upper lung lobe. Spontaneous
pneumothoraces occur most often in young men (during the second
or third decade) who have a tall, slender body habitus. Symptoms
include pain and difficulty breathing. Diagnosis should be suspected any
time there are absent or decreased breath sounds in an area that is
hyper-resonant to percussion. Chest x-ray will show a
radiolucency (dark area). In a large pneumothorax with complete lung
collapse, this area of radiolucency will appear throughout the entire lung
field; but in a small pneumothorax it can be a long, narrow area
corresponding to the space between the chest wall and the partially
collapsed lung.
If the patient is relatively asymptomatic or at least able to tolerate
symptoms, and the pneumothorax appears radiographically to have
caused lung collapse of 25% or less for the involved lung, conservative
management may be utilized. The pleural air of a pneumothorax will
usually resolve at the rate of approximately 1% per day. Larger or
more symptomatic pneumothoraces may be treated with insertion of a
chest tube.
A lobar infiltrate (choice A) could signify a lobar pneumonia, but is
unlikely in this patient because he is afebrile and the onset of symptoms
was very sudden.
A lateral (peripheral) wedge-shaped opacity (choice C) can sometimes be
seen after a pulmonary infarction from a pulmonary embolus.
Hyperresonance on percussion is an unlikely finding for pulmonary

embolism, and this patient does not appear to have any risk factors for a
predisposing deep venous thrombosis or pulmonary embolus.
Fluid in the left costophrenic angle (choice D) could be caused in a young
adult by pneumonia, trauma, even viral infection, etc. Also, there would
be diminished breath sounds on physical examination. However,
the physical examination would include dullness to percussion
rather than hyper-residence; and the chest x-ray would be
unmistakably different, showing pleural fluid rather than free air.
Hyperinflation of the lung fields (choice E) usually accompanies
an obstructive disorder, such as asthma (during an attack) or
emphysema
tuberculosis (TB) as evidenced by the presenting signs of cough with bloody sputum, fevers, and night
sweats and confirmation of acid-fast bacilli seen on Ziehl-Neelsen stain. The patient also works in prison and homeless shelters,
where TB can be prevalent.
TB is the most common opportunistic infection affecting HIV-positive individuals and is the most common cause of death
in patients with AIDS. HIV-infected persons with latent TB are 20-30 times more likely to develop active TB than those who are
immunocompetent. Once infection occurs, the risk of rapid progression of TB among persons with HIV infection is greater because HIV
impairs the host's ability to contain the new TB infection. In turn, coinfection with TB increases the risk of HIV progression and death.
Worldwide, approximately 15% of TB patients have HIV coinfection and that number can reach as high as 50-80% in parts of sub-Saharan
Africa. In the United States, in TB-infected individuals with known HIV test results, 8.6% were HIV coinfected, with foreign born persons,
Asian Americans, African Americans, and Hispanics being disproportionally affected.
This patient most likely has HIV-positive/AIDS-related tuberculosis (TB)and most likely has decreased CD4 cell counts. Defective
cell-mediated immunity occurs when circulating CD4 lymphocytes are decreased and are unable to suppress the spread of the certain
organisms, which leads to fungal infection (oral thrush) or reactivation of TB, Varicella zoster, and HHV8 (Kaposi sarcoma). Patients with
decreased cell-mediated immunity may form a few caseating granulomas and have an atypical presentation with poorly formed
granulomas and collections of macrophages. There is increased exposure to TB within crowded areas and among people with poor
nutrition or hygiene (e.g., homeless shelters, prisons).
Common variable immunodeficiency, CVID (choice B) is one of the most common forms of congenital immune deficiency syndrome. It is
a defect in humoral immunity and is due to inability of lymphocytes to mature into plasma cells. Levels of immunoglobulin
isotypes (IgA, IgG, IgM, IgE) vary (decreased or normal). Cell-mediated immunity (on which granuloma formation is largely dependent) is
intact. Typical pathogens in CVID include encapsulated bacteria (Streptococcus pneumoniae, and H. influenza) and Moraxella
catarrhalis in the lungs, and Giardia,Salmonella, and Campylobacter in the GI tract. These would also not be positive on acid fast staining.
Cystic fibrosis (choice C) causes mucus accumulation within the bronchial airways and predisposes to recurrent
bronchopneumonia (Pseudomonas, Burkholderia cepacia, and Staphylococcus aureus) and development of bronchiectasis. This patient
did not have recurrent pulmonary infections or bronchiectasis.
Depressed level of consciousness (choice D) predisposes to aspiration of oropharyngeal flora and/or gastric contents and
development of aspiration pneumonia. Anaerobic bacteria (Fusobacterium, Bacteroides) and Klebsiellaare commonly cultured. These
would also not be positive on acid fast staining. An abscess and sheets of macrophages are often observed, but not necrotizing
granulomas (unless there are additional predisposing conditions, such as AIDS). Conditions of depressed levels of consciousness include
seizure disorders, chronic alcoholism, severe neurologic disorders, dementia, and coma.
Sarcoidosis (choice E) is a diagnosis of exclusion. The condition is characterized by widespread noncaseating granuloma formation
in various organs without apparent cause. Lungs and hilar lymph nodes are among the most commonly affected organs. Patients would
have low-grade fever and dyspnea rather than night sweats and chills. Hypercalcemia and elevated angiotensin converting enzyme levels
would be present. Extrapulmonary symptoms include uveitis and erythema nodosum. Acid fast and silver stains are negative for
organisms.
MEFVs are integral to our laboratory assessment of pulmonary function. Knowing how to interpret MEFVs is essential, but it
can also be quite simple if you are able to learn pattern recognition for four principal patterns:

Normal

Restrictive:normal in contour, but reduced in scale(see the MEFV for this case scenario)

Obstructive: may range from mildly abnormal small/peripheral airway disease deficit, with only abnormal slope at the tail of
the curve vs. severe, advance airway disease with a very dramatically abnormal appearance; but in all cases, the inspiratory
portion of the loop will be normal.

Upper airway obstructive: a distinctly different appearance from the other three curves, with uniform flattening of both
the inspiratory and expiratory phases of the loop; associated with a unique set of differential diagnosis possibilities:
goiter and other causes of tracheal compression; obstructive sleep apnea-related lesions and other upper airway pathology;
and often requiring prompt therapeutic intervention for a potentially life-threatening situation.

Returning to this particular case, the dashed MEFV curve is typical of a patient with a restrictive physiologic deficit. This restrictive
pattern is usually due to diffuse infiltrative lung disease such as interstitial fibrosis, but may also occasionally be due to diffuse
pleural disease, chest wall deformity, or neuromuscular disease. For purposes of answering this question correctly, we have been
explicitly told that the restrictive MEFV belongs to a patient with pulmonary disease, not one of the extra pulmonary-alternative
diagnoses.
We know that the airways are tethered more strongly to the lung parenchyma in infiltrative lung diseases likeinterstitial
fibrosis (and the overall elasticity of the lung is increased). This, in turn, causes the airways to be held open to a greater
extent at each lung volume (i.e., radial traction is greater). This increase in radial traction and subsequent increase in airway
diameter causes the maximum expiratory flow rate to be higher at any given lung volume, as shown by the dashed curve in the
diagram.
The increase in fibrous material in the lung causes the pulmonary compliance (choice A) to decrease (increased elasticity) and
inspiration is impaired.
Also, please remember that in restrictive lung diseases, the residual volume (choice C), total lung capacity (choice D), vital
capacity (choice E), and FEV1 are all decreased. However, since the FEV1 often decreases slightly less than the FVC, the FEV1/FVC
ratio will either remain normal or be slightly increased.
Updated on 01/19/16
(choices B) are associated with multiple myeloma (Bence-Jones proteins), not minimal change disease. They are filtered through
the glomeruli, accumulate in renal tubules, and cause proteinuria, tubular damage, and renal failure. Light chain nephropathy can, of
course, present with nephrotic syndrome.
Neutrophils (choice D) can be seen with any bacterial urinary tract infection. Neutrophil casts reflect accumulation of neutrophils
within renal tubule lumen, such as that seen in pyelonephritis, whereas scattered neutrophils in urine would be seen in lower locations
such as ureter, bladder, and urethra.
Red blood cells (choice E) in urine (hematuria) are associated with conditions such as in trauma, nephritic syndrome, bacterial infection
(cystitis), and malignancies of the kidney and bladder. Red blood cell casts reflect accumulation of red cells within renal tubule
lumen (nephritic syndrome), whereas scattered red blood cells would be extravasated with lower locations such as the ureter,
bladder, and urethra.
he correct answer is D. This patient has clinical signs of moderate dehydration. He is confused, with no evidence of head trauma. It
has only been 30 minutes since the accident, so dehydration is most likely unrelated to the accident. A patient who is morbidly
obese with excessive urination suggests type 2 diabetes mellius (DM). Hyperglycemia, as would occur with DM, can prevent the
complete reabsorption of glucose in the proximal tubule. This would also cause a reduced reabsorption of water and electrolytes in the
proximal tubule. The increased delivery of fluid and electrolytes to the loop of Henle overloads this segment of the nephron
and reduces its ability to maintain the medullary osmolar gradient. This gradient is required for the antidiuretic hormone (ADH)induced reabsorption of water from the collecting duct. ADH simply places water channels in membranes lining the collecting ducts,
which then permits the passive reabsorption of water. Any failure at the level of the collecting duct or the loop of Henle reduces the
ability of the kidney to form a concentrated urine. In the nephrogenic form of diabetes insipidus, the patient would also fail to respond to
the ADH, but urine osmolality would be low, rather than elevated.
Why is type 2 diabetes mellitus the best choice from among the options given? This patient is hypernatremic with normal bicarbonate.
Poorly managed type 2 DM is most likely to produce ahyperglycemic, hyperosmotic, non-ketotic state (HHNS). DKA can occur, but
it is not the most common presentation. HHNS usually is associated with a prolonged period of osmotic diuresis; most often water loss
exceeds sodium loss, so they have hypertonic dehydration. So, it is quite likely for a person to have undiagnosed type 2 DM.
Hyperglycemia increases the filtered load of glucose. If the filtered load exceeds the glucose transport maximum, glucose will appear in
the urine; this causes an osmotic diuresis. The patient becomes dehydrated despite compensatory increases of ADH and the reninangiotensin-aldosterone system (RAAS). The dehydration usually will be associated with hypernatremia; the body is avidly reabsorbing
sodium chloride to attempt to conserve fluid. The osmotic diuresis overwhelms this response.
None of the other choices would produce the described interference with ADH action.
Volume expansion tends to cause metabolic acidosis. It is difficult to consume enough sodium(choice A) to cause hypenatremia if the
kidneys are healthy. Volume expansion and metabolic acidosis are likely so long as water is also available to be consumed.
Hypoaldosteronism (choice C) will not cause hypernatremia; it will cause hyponatremia and possibly also metabolic acidosis. In addition,
the hyponateremia with deficient aldosterone is secondary to compensatorily increased ADH (ADH increased because of volume loss
caused by low aldosterone). If a patient has hypernatremia, aldosterone deficiency is not likely to be responsible.

Hyperthyroidism (choice B) and vitamin D (choice E) deficiency have no direct connection to his condition.
The correct answer is E. Creatinine is metabolic waste product that muscle produces continually and must be excreted by the kidneys
at an equivalent rate. Creatinine excretion is largely a passive process. Creatine filters freely across the glomerular filtration barrier and
passes through the tubule without being reabsorbed and is then excreted in urine. When plasma creatinine concentrations rise, excretion
rates necessarily rise also.
The term clearance is a measure of the kidneys ability to excrete waste products and is defined as the volume of plasma that is
completely cleared of any given substance per unit time. Note that the term does not reference concentration, only plasma
volume. Creatinine clearance is calculated from a knowledge of plasma and urinary creatine concentrations using the clearance
equation.
Thus, creatinine clearance is calculated as
CCr = (UCr x V)/PCr
where CCr = creatinine clearance (mL/min), UCr = urinary concentration of creatinine (mol/L or mg/dL), V = urine flow rate (mL/min), and
PCr is plasma concentration of substance X (mol/L or mg/dL).
In the patients case, the volume of blood cleared of creatinine per min dropped over the course of a year from 100 mL to 50 mL a twofold decrease. Since excretion rate must match the rate of creatinine production over the long term, U Cr can be considered a constant. The
reciprocal relationship between clearance and plasma concentration means that when C Crdecreases two-fold, PCr must rise twofold (choice E).
For the purpose of demonstration, assume that the patients serum creatinine level originally was 50 micromol/L. If his original creatinine
clearance were 100 mL/min, then he was excreting 5 micromol/min (i.e., the amount of creatinine contained in 100 mL of blood).
Glomerulonephritis has caused the patients glomerular filtration rate (GFR) to drop, meaning that less creatinine is excreted per
minute. An acute two-fold decrease in GFR means that that now only 2.5 micromoles/min are currently being excreted, which is less than
the rate of creatinine production. Plasma creatinine levels inevitably rise as a result (see figure).

When PCr reaches 100 micromol/L (a two-fold increase over baseline), the normal urinary excretion rate of 5 micromol/min is restored.
Because creatinine is freely filtered at the glomerulus and plasma and urine concentrations are easy to measure, creatinine clearance
is commonly used clinically to estimate GFR. Creatinine is actively secreted by the proximal tubule which introduces a small
error (~10-40%), but changes in CCr can be a useful indicator of kidney injury and disease. In practice, urine is collected over a 24 hour
period to determine UCr and urine flow rate. When corrected for body surface area, normal values for GFR are ~130 and 120
mL/min/1.73 m2 for men and women, respectively, although there may be considerable variation with sex and age even within a single
individual.
The blood urea nitrogen concentration (choice A) increases when GFR is reduced.
At steady state, creatinine production and excretion rates are constant, so choices B and C are incorrect.
Creatinine is not reabsorbed during passage through the renal tubule, which excludes choice D.
Updated on 03/15/16

correct answer is B. This patient has developed disseminated intravascular

coagulation (DIC) as a complication ofgram-negative sepsis. In DIC, widespread
clotting and fibrinolysis occur simultaneously throughout the body. Severe DIC can
produce thrombosis in many renal vessels and cause diminished vascular
perfusion, leading to diffuse cortical necrosis.Obstetric emergencies (e.g.,
abruptio placentae) is another frequent cause. Massive cortical necrosis can lead to
sudden anuria, and can rapidly cause uremic death.
The

Low platelets, low fibrinogen, increased PT and PTT, and presence of fibrin
degradation products suggest DIC. This process ultimately leads
to consumption deficiency of clotting factors (which explains the prolonged PT
and PTT) and platelets. DIC may be secondary to liberation of tissue
factors due to infections (gram-negative sepsis), obstetric catastrophes, neoplasms
(acute promyelocytic leukemia), hemolysis, fat embolism, severe trauma, endothelial
damage, and pancreatitis.
Cortical scarring (choice A), or benign nephrosclerosis, is a chronic change seen
with diabetes mellitus type 2 and hypertension. Microscopically, there
is hyaline arteriolosclerosis, glomerulosclerosis, tubular atrophy, and
interstitial fibrosis. Laboratory findings include azotemia, proteinuria, and
hematuria. Although, the patient has a history of diabetes mellitus, the gramnegative sepsis and hypotensive event causes an acute hypoperfusion effect on the
kidney, resulting in the diffuse cortical necrosis.
Patchy papillary necrosis (choice C) is seen in sickle cell disease or
trait, chronic analgesic (NSAIDs) use, diabetes mellitus, renal stones within
the urinary pelvis, and pyelonephritis, not DIC.
Uric acid stones (choice D) can be associated with gouty nephropathy or tumor
lysis syndrome. The stones develop slowly in an acidic urine and are not
associated with DIC.
Wedge-shaped necrosis (choice E) is usually focal and is seen with acute renal
infarct. Although multiple small cortical infarcts can occur in DIC, the classic wedge
shaped infarct is usually due to a trauma, thrombus, or
embolus (endocarditis, atrial fibrillation, atheroscleroti
This patient has nephrogenic diabetes insipidus. Diabetes insipidus (DI) is
characterized by the excretion of abnormally large volumes of dilute
urine (polyuria)with a commensurate increase in fluid intake (polydipsia). There
are two types:

Neurogenic (central) DI (choice C), which is the most common type, is due
toinadequate secretion of antidiuretic hormone (ADH; also
called vasopressin).

Nephrogenic DI (choice B) is caused by failure of the kidney to

produce concentrated urine even when adequate ADH is secreted.

Neurogenic DI is most commonly caused by trauma or surgery to posterior

pituitary orhypothalamus. Alcohol consumption very rapidly causes decreased
secretion of ADH, so it resembles central DI; this effect fades as alcohol is quickly
cleared from the body, however.
Nephrogenic DI can be genetic, mostly due to defects in vasopressin V2
receptors oraquaporin channels; only a small percentage is inherited. Most

cases of nephrogenic DI are acquired because of drug treatment, with

agents such as lithium, demeclocycline (for treatment of SIADH),
or fluoride (fluorocarbon anesthetics).
Overnight water restriction is a common provocative test. In normal subjects,
urine flow decreases and urine osmolarity increases to prevent dehydration and
plasma hyperosmolarity. If the urine remains dilute and the urine volume remains
high despite water restriction, this is evidence that the kidneys are unable to
appropriately concentrate urine. Placing this patient on overnight water restriction
caused severe dehydration and a greatly elevated plasma sodium concentration. The
key point here is that there was polyuria despite a very high level of ADH; therefore,
this patient has nephrogenic DI (choice B).
The classic way to distinguish between nephrogenic and neurogenic/central
DI is toadminister ADH. If there is a response after ADH has been administered (an
increase in urine osmolarity), the patient has neurogenic/central DI. If there is no
response, the patient has nephrogenic DI.
Neurogenic/central DI can be treated with administration of ADH. Nephrogenic DI is
harder to treat because the kidney is not responsive to the ADH secreted. This
condition rarely causes severe problems as long as the person has plenty of water to
drink. Pharmacologic treatment for nephrogenic diabetes includes mild diuretics such
as hydrochlorothiazide and amiloride. The theory is that these drugs block sodium
reabsorption distally and may stimulate additional water reabsorption at the
proximal convoluted tubule, though the precise mechanism is unclear.
Addison disease (choice A) results either destruction of the adrenal cortex or from a
failure of the hypothalamic-pituitary axis that prevents adrenocorticotropic hormone
(ACTH) production. The resulting lack of aldosterone production leads to decreases
in sodium reabsorption, allowing large amounts of sodium to be lost into the urine.
Polyuria and polydipsia are not characteristic of Addison disease. Also, decreased
mineralocorticoids will not cause the hypernatremia that was seen in this patient, but
instead would cause mild hyponatremia. Additional metabolic findings
include hyperkalemia and metabolic acidosis.
Diabetes mellitus (choice D), which can also be associated with polyuria and
polydipsia, is incorrect, because these patients can still concentrate their urine
following water deprivation (unlike the patient in the vignette). The polyuria seen in
these patients results from osmotic diuresis due to glucosuria.
Fanconi syndrome (choice E) is associated with various defects in the proximal
tubule that prevent normal reabsorption of glucose, amino acids, uric acid,
phosphate, and bicarbonate. Large amounts of glucose (as well as other
substances normally reabsorbed in the proximal tubule) are usually present in the
urine; however these patients have no difficulty with concentrating their urine (ruling
out this syndrome for this patient). Inherited forms are usually identified early in life;
in children, cystinosis is the most common cause. Other causes includeWilson
disease, galactosemia, and glycogen storage diseases. Acquired causes
include expired tetracyclines, tenofovir, ifosfamide, and lead poisoning.
Urinary bicarbonate losses with Fanconi syndrome present as type 2 (proximal)
renal tubular acidosis (RTA).j
Psychogenic polydipsia (choice F) is a rare condition in which patients display
excessive thirst. It is can be found in patients with mental illnesses such
as schizophrenia. Unlike the patient described in the vignette, patients with
psychogenic polydipsia will present with hyponatremia (due to normal ADH function
and excessive water intake) and low levels of ADH (because of the hyponatremia).
These patients should also be able to concentrate their urine with water deprivation.
SIADH (choice G) is characterized by hyponatremia and hypo-osmolality resulting
from inappropriate secretion of ADH, which causes impaired water excretion. Thus,
the hyponatremia in SIADH patients results from excess water rather than a sodium

deficiency. The fact that this patient is hypernatremic rules this out. SIADH is caused
by many drugs (e.g.,SSRIs, tricyclic antidepressants, monoamine oxidase
inhibitors, carbamazepine, antipsychotics, benzodiazepines, methadone,
nicotine). Some tumors, especially small cell carcinoma of the lung, can
produce SIADH.
he correct answer is B. This patient has a tumor of the kidney and most likely has Wilms tumor (nephroblastoma), the most
common malignant renal tumor in children. The tumor is commonly present in children less than age 5 and has a 90% survival rate,
thanks to modern management. Note: the differential diagnosis for an abdominal mass in a child < 5 years of age also includes
neuroblastoma, which arises from the adrenal gland. Neuroblastoma is the most common solid tumor of infancy and childhood.
Microscopically, there is a triphasic pattern: embryonic undifferentiated cells (blastema), immature glomerular and tubular structures
(epithelium), and a spindle-cell stroma (mesenchyme). They may also contain smooth muscle, striated muscle, bone, cartilage, fat, and
fibrous tissue. On gross examination, the tumor appears as a very large, well-demarcated, tan mass, usually occurring unilaterally, but
may be bilateral if familial. It can be caused by deletion of a tumor suppressor gene (WT1) on chromosome 11p13 or (WT2) on
chromosome 11p15.
Wilms tumor generally presents as a large, unilateral mass. Other symptoms include abdominal pain, hypertension (because of renin
release), and hematuria. The majority of cases are sporadic, but a small percent are occur as part of multiple malformation syndromes,
such as WAGR (Wilms tumor, Anirida, Genital abnormalities, mental and motor Retardation), Denys-Drash syndrome, and BeckwithWiedermann syndromes.
Abundant clear cells (choice A) are a feature of renal cell carcinoma (clear cell type). Renal cell carcinoma is usually seen as a
sporadic (non-inherited) tumor in older adults who have a history of tobacco smoking, chronic renal failure on hemodialysis, chronic
analgesic use, and asbestos exposure. Gross examination shows a yellow tumor, and if present near the renal hilum, can invade the renal
vein and spread hematogenously to the right heart. It presents with the classic triad of hematuria, palpable mass, and flank pain. Many
patients have accompanying paraneoplastic syndromes. It also develops in nearly 40% of patients with von Hippel-Lindau disease.
Eosinophilic cells packed with mitochondria (choice C) suggest oncocytoma, which are often benign. On light microscopy, epithelial
cells have an eosinophilic and granular cytoplasm. Electron microscopy confirms the presence of increased mitochondria. Oncocytomas
can also occur in the salivary and thyroid glands.
Hamartomatous blood vessels (choice D) suggest angiomyolipoma, a benign tumor of the kidney which can occur sporadically or is
associated with tuberous sclerosis.
Primitive cells with neuropil (choice E) suggest neuroblastoma, a malignant neuroendocrine tumor of the adrenal medulla. It is
common among children age less than 5 years and can present with high blood pressure, opsoclonus myoclonus, and distant metastases.
Histologically, tumor cells are small, with blue cytoplasm, surrounding neuropil, and forming rosettes (Homer-Wright rosettes). It is
associated with N-myc oncogene amplification
he correct answer is B. This patient has bilateral renal infarction; a very dangerouscomplication of aortic dissection, which
classically presents as described in the question stem. The dissection usually progresses distally to involve the major arteries
arising from the aorta. Less often, the dissection may run proximally. In this patient, distal progression of the aortic dissection
caused bilateral renal artery occlusion, resulting in renal hypoperfusion, infarction with flank pain and hematuria.
Aortic dissection is associated with hypertension, Marfan disease, or Ehlers-Danlos syndrome and classically presents with a sharp and
tearing pain that radiates to the back (as seen in our patient); the location of the pain moves as the dissection progresses.
Acute glomerulonephritis (choice A) is characterized by hematuria, red cell casts, and often, proteinuria and edema. This syndrome
typically develops over days, not hours, and would not be expected to result from dissecting aortic aneurysm.
Polycystic kidney disease (choice C) is a lifelong condition characterized by bilateral enlargement and polycystic changes in the
kidneys. Spontaneous rupture of individual cysts in the kidneys can cause flank pain and hematuria, however the pain is usually
unilateral and the other signs and symptoms described here would not be present. It clinically presents by middle-age with
hypertension, flank pain, and hematuria, and can later progress to renal failure.
Pyelonephritis (choice D) is an infection of the kidney that can develop as a complication of bacterial endocarditis (hematogenous
spread), as a consequence of an ascending urinary tract infection or vesicoureteral reflux, but would not be expected to result from aortic
dissection. It would present with fever, chills, malaise, flank pain, and pyuria, but not present with as initial chest pain and
hematuria.
Sickle cell crisis (choice E) can cause papillary necrosis of the kidneys with hematuria, but there is no indication that this patient
has sickle-cell anemia. Patients with sickle cell trait would have asymptomatic hematuria.