gastrointestinal Pathology

Question 1

Sialolithiasis

Stone(s) in salivary gland duct. Can occur in 3

major salivary glands (parotid, submandibular,

sublingual). Single stone more common in

submandibular gland (Wharton duct).

Presents as recurrent pre-/periprandial pain and

swelling in affected gland.

Caused by dehydration or trauma.

Treat conservatively with NSAIDs, gland

massage, warm compresses, sour candies (to

promote salivary flow).

Sialadenitis—inflammation of salivary gland due

to obstruction, infection, or immune-mediated

mechanisms.

Question 2

Salivary gland tumors

Most commonly benign and in parotid gland. Tumors in smaller glands more likely malignant.

Typically present as painless mass/swelling. Facial pain or paralysis suggests malignant

involvement of CN VII.

ƒ. Pleomorphic adenoma (benign mixed tumor)—most common salivary gland tumor A .

Composed of chondromyxoid stroma and epithelium and recurs if incompletely excised or

ruptured intraoperatively. May undergo malignant transformation.

ƒ.Mucoepidermoid carcinoma—most common malignant tumor, has mucinous and squamous

components.

ƒ.Warthin tumor (papillary cystadenoma lymphomatosum)—benign cystic tumor with germinal

centers. Typically found in smokers. Bilateral in 10%; multifocal in 10%.

Answer 2

Achalasia

Failure of LES to relax due to loss of myenteric

(Auerbach) plexus due to loss of postganglionic

inhibitory neurons (which contain NO and

VIP).

Manometry findings include uncoordinated

or absent peristalsis with high LES resting

pressure Ž progressive dysphagia to solids and

liquids (vs obstruction—solids only). Barium

swallow shows dilated esophagus with an area

of distal stenosis (“bird’s beak”

 risk of esophageal cancer.

2° achalasia (pseudoachalasia) may arise

from Chagas disease (T cruzi infection) or

extraesophageal malignancies (mass effect or

paraneoplastic).

Question 3

Esophageal pathologies

Boerhaave syndrome

Eosinophilic esophagitis

Esophageal strictures

Esophageal varices

Esophagitis

Gastroesophageal reflux disease

Mallory-Weiss syndrome

Plummer-Vinson syndrome

Sclerodermal esophageal dysmotility

Answer 3

Boerhaave syndrome-Transmural, usually distal esophageal rupture with pneumomediastinum due to

violent retching. Subcutaneous emphysema may be due to dissecting air (crepitus may be felt in

the neck region or chest wall). Surgical emergency.

Eosinophilic esophagitis-Infiltration of eosinophils in the esophagus often in atopic patients. Food allergens –>dysphagia, food impaction. Esophageal rings and linear furrows often seen on endoscopy. Typically unresponsive to GERD therapy.

Esophageal varices- Dilated submucosal veins in lower 1 ⁄3 of esophagus A 2° to portal hypertension. Common in cirrhotics, may be source of life-threatening hematemesis.

Esophagitis-Associated with reflux, infection in immunocompromised (Candida: white pseudomembrane; HSV-1: punched-out ulcers; CMV: linear ulcers), caustic ingestion, or pill esophagitis (eg, bisphosphonates, tetracycline, NSAIDs, iron, and potassium chloride).

Gastroesophageal reflux disease-Commonly presents as heartburn, regurgitation, dysphagia. May also present as chronic cough, hoarseness (laryngopharyngeal reflux). Associated with asthma. Transient decreases in LES tone.

Question 4

Esophageal pathologies

Mallory-Weiss syndrome-Partial-thickness mucosal lacerations at gastroesophageal junction due to severe vomiting. Often presents with hematemesis. Usually found in alcoholics and bulimics

Plummer-Vinson syndrome- Triad of Dysphagia, Iron deficiency anemia, and Esophageal webs. May be associated with glossitis. Increased risk of esophageal squamous cell carcinoma (“Plumbers DIE ”).

Sclerodermal esophageal dysmotility- Esophageal smooth muscle atrophy–> decreased LES pressure and dysmotility –> acid reflux and dysphagia–> stricture, Barrett esophagus, and aspiration. Part of CREST syndrome.

Question 5

Barrett esophagus-Specialized intestinal metaplasia —replacement of nonkeratinized stratified squamous epithelium with intestinal epithelium (nonciliated columnar with goblet cells [stained blue in B ))in distal esophagus. Due to chronic gastroesophageal reflux disease (GERD). Associated with

increased risk of esophageal adenocarcinoma.

Answer 5

Esophageal cancer-Typically presents with progressive dysphagia (first solids, then liquids) and weight loss; poorprognosis.

Squamous cell carcinoma- affects upper 2/3 of esophagus, risk factors: Alcohol, hot liquids, caustic

strictures, smoking, achalasia.

Adenocarcinoma-affects lower 1/3 of esophagus. risk factors: Chronic GERD, Barrett esophagus, obesity, smoking, achalasia

Question 6

Gastritis

Acute gastritis- Erosions can be caused by:

ƒ. NSAIDs—decreased PGE2 –> decreased gastric mucosa

protection

ƒ. Burns (Curling ulcer)—hypovolemia–> mucosal ischemia

ƒ. Brain injury (Cushing ulcer)—increased vagalstimulation –> increased ACh–> increased H+ production

Answer 6

Chronic gastritis-Mucosal inflammation, often leading to atrophy (hypochlorhydria–>hypergastrinemia) and intestinal metaplasia (increased risk of gastric cancers).

H. Plyori-affects antrum first and spread to body of stomach

autoimmune- autoantibodies to the H/K ATPase on parietal cells and to intrinsic factor. increased risk of pernicious anemia

affects the body/fundus of stomach

Question 7

Ménétrier disease

Hyperplasia of gastric mucosa –> hypertrophied rugae (look like brain gyri A ). Causes excess mucus production with resultant protein loss and parietal cell atrophy with decreased acid production.

Precancerous.

Presents with epigastric pain, anorexia, weight loss, vomiting, edema (due to protein loss).

Answer 7

Gastric cancer

Most commonly gastric adenocarcinoma; lymphoma, GI stromal tumor, carcinoid (rare). Early aggressive local spread with node/liver metastases. Often presents late, with weight loss, abdominal pain, early satiety, and in some cases acanthosis nigricans or Leser-Trélat sign. Associated with blood type A

ƒ Intestinal—associated with H pylori, dietary nitrosamines (smoked foods), tobacco smoking, achlorhydria, chronic gastritis. Commonly on lesser curvature; looks like ulcer with raised margins.

ƒ Diffuse—not associated with H pylori; signet ring cells (mucin-filled cells with peripheral nuclei) ; stomach wall grossly thickened and leathery (linitis plastica).

Virchow node—involvement of left supraclavicular node by metastasis from stomach.

Krukenberg tumor—bilateral metastases to ovaries. Abundant mucin-secreting, signet ring cells

Sister Mary Joseph nodule—subcutaneous periumbilical metastasis.

Question 8

Peptic ulcer disease

what is the differences bewteen gastric ulcer and duodenal ulcer

when do you feel pain

what percentage of H. pylori is involved

mechanism?

other causes?

risk of carcinoma?

Answer 8

Gastric ulcer

PAIN Can be Greater with meals—weight loss

H PYLORI INFECTION ~ 70%

MECHANISM decreased mucosal protection against gastric acid

OTHER CAUSES NSAIDs

RISK OF CARCINOMA increased

OTHER Biopsy margins to rule out malignancy

Duodenal ulcer

PAIN Decreases with meals—weight gain

H PYLORI INFECTION ~ 90%

MECHAISM decreased mucosal protection or increased gastric acid secretion

other causes: Zollinger-Ellison syndrome

Risk of Carcinoma: Generally benign

Other: Hypertrophy of Brunner glands

Question 9

Ulcer complications

Hemorrhage-Gastric, duodenal (posterior > anterior). Most common complication. Ruptured gastric ulcer on the lesser curvature of stomach –> bleeding from left gastric artery. An ulcer on the posterior wall of duodenum –> bleeding from gastroduodenal artery.

Obstruction-Pyloric channel, duodenal.

Perforation-Duodenal (anterior > posterior). May see free air under diaphragm with referred pain to the shoulder via irritation of phrenic nerve.

Answer 9

Malabsorption syndromes

Celiac disease

Lactose intolerance

Pancreatic insufficiency

Tropical sprue

Whipple disease

Question 10

celiac disease- Gluten-sensitive enteropathy, celiac sprue. Autoimmune-mediated intolerance of gliadin (gluten protein found in wheat)–> malabsorption and steatorrhea. Associated with HLA-DQ2, HLA-DQ8

Findings: IgA anti-tissue transglutaminase (IgA tTG), anti-endomysial, anti-deamidated gliadin peptide antibodies; villous atrophy,crypt hyperplasia, intraepithelial lymphocytosis. Moderately increased risk of malignancy (T-cell lymphoma)

decreased mucosal absorption primarily affects distal duodenum and/or proximal jejunum.

d-xylose test: passively absorbed in proximal small intestine; blood and urine levels decreased with mucosa defects or bacterial overgrowth, normal in pancreatic insufficiency

Treatment: gluten-free diet.

Answer 10

Lactose intolerance

Normal-appearing villi, except when 2° to injury at tips of villi (eg, viral enteritis). Osmotic diarrhea with decreased stool pH (colonic bacteria ferment lactose).

Lactose hydrogen breath test

Pancreatic insufficiency

Due to chronic pancreatitis, cystic fibrosis, obstructing cancer. Causes malabsorption of fat and fat-soluble vitamins (A, D, E, K) as well as vitamin B12.

decreased duodenal pH (bicarbonate) and fecal elastase.

Question 11

Tropical sprue

Similar findings as celiac sprue (affects small bowel), but responds to antibiotics. Cause is unknown, but seen in residents of or recent visitors to tropics

decreased mucosal absorption affecting duodenum and jejunum but can involve ileum with time. Associated with megaloblastic anemia due to folate deficiency and, later, B12 deficiency

Answer 11

Whipple disease

Infection with Tropheryma whipplei (intracellular gram ⊕); PAS ⊕ foamy macrophages in intestinal lamina propria , mesenteric nodes. Cardiac symptoms, Arthralgias, and Neurologic symptoms are common. Diarrhea/steatorrhea occur later in disease course. Most common in older men.

Question 12

Crohn disease

LOCATION Any portion of the GI tract, usually the terminal ileum and colon. Skip lesions, rectal sparing.

GROSS MORPHOLOGY Transmural inflammation –> fistulas. Cobblestone mucosa, creeping fat, bowel wall thickening (“string sign” on barium swallow x-ray ), linear ulcers, fissures)

MICROSCOPIC MORPHOLOGY Noncaseating granulomas and lymphoid aggregates. Th1 mediated.

complications: fistula

INTESTINAL MANIFESTATION Diarrhea that may or may not be bloody.

EXTRAINTESTINAL MANIFESTATIONS: Kidney stones (usually calcium oxalate), gallstones. May be ⊕ for anti-Saccharomyces cerevisiae antibodies (ASCA).

TREATMENT Corticosteroids, azathioprine, antibiotics (eg, ciprofloxacin, metronidazole), infliximab, adalimumab.

Answer 12

Ulcerative colitis

LOCATION Colitis = colon inflammation. Continuous colonic lesions, always with rectal involvement.

GROSS MORPHOLOGY Mucosal and submucosal inflammation only. Friable mucosa with superficial and/or deep ulcerations (compare normal B with diseased C ). Loss of haustra –> “lead pipe”

MICROSCOPIC MORPHOLOGY Crypt abscesses and ulcers, bleeding, no granulomas. Th2 mediated.

complications: Fulminant colitis, toxic megacolon, perforation.

INTESTINAL MANIFESTATION Bloody diarrhea.

EXTRAINTESTINAL MANIFESTATIONS 1° sclerosing cholangitis. Associated with p-ANCA.

TREATMENT 5-aminosalicylic preparations (eg, mesalamine), 6-mercaptopurine, infliximab, colectomy

Question 13

For Crohn, think of a fat granny and an old crone skipping down a cobblestone road away from the wreck (rectal sparing

Answer 13

Ulcerative colitis causes ULCCCERS:

Ulcers

Large intestine

Continuous,

Colorectal carcinoma,

Crypt abscesses

Extends proximally

Red diarrhea

Sclerosing cholangitis

Question 14

Diverticulum-Blind pouch protruding from the alimentary tract that communicates with the lumen of the gut. Most diverticula (esophagus, stomach, duodenum, colon) are acquired and are termed “false diverticula.”

“True” diverticulum—all gut wall layers outpouch (eg, Meckel).

“False” diverticulum or pseudodiverticulum— only mucosa and submucosa outpouch. Occur especially where vasa recta perforate muscularis externa.

Answer 14

Diverticulosis

Many false diverticula of the colon , commonly sigmoid. Common (in ~ 50% of people > 60 years). Caused by INCREASED intraluminal pressure and focal weakness in colonic wall. Associated with obesity and diets low in fiber, high in total fat/red meat.

Complications include diverticular bleeding (painless hematochezia), diverticulitis

Diverticulitis Inflammation of diverticula with wall thickening classically causing LLQ pain, fever, leukocytosis. Treat with antibiotics.

Complications: abscess, fistula (colovesical fistula –> pneumaturia), obstruction (inflammatory stenosis), perforation (–> peritonitis).

Question 15

Zenker diverticulum

Pharyngoesophageal false diverticulum. Esophageal dysmotility causes herniation of mucosal tissue at Killian triangle between the thyropharyngeal and cricopharyngeal parts of the inferior pharyngeal constrictor. Presenting symptoms: dysphagia, obstruction, gurgling, aspiration, foul breath, neck mass. Most common in elderly males

Elder MIKE has bad breath.

Elderly

Males

Inferior pharyngeal constrictor

Killian triangle

Esophageal dysmotility

Halitosis

Answer 15

Meckel diverticulum

True diverticulum. Persistence of the vitelline (omphalomesenteric) duct. May contain ectopic acid–secreting gastric mucosa and/or pancreatic tissue. Most common congenital anomaly of GI tract. Can cause hematochezia/ melena (less commonly), RLQ pain, intussusception, volvulus, or obstruction near terminal ileum.

Contrast with omphalomesenteric cyst = cystic dilation of vitelline duct

Diagnosis: pertechnetate study for uptake by heterotopic gastric mucosa.

The rule of 2’s:

2 times as likely in males.

2 inches long.

2 feet from the ileocecal valve.

2% of population.

Commonly presents in first 2 years of life.

May have 2 types of epithelia (gastric/ pancreatic).

Question 16

Hirschsprung disease

Congenital megacolon characterized by lack of ganglion cells/enteric nervous plexuses (Auerbach and Meissner plexuses) in distal segment of colon. Due to failure of neural crest cell migration. Associated with mutations in RET

Presents with bilious emesis, abdominal distention, and failure to pass meconium within 48 hours –> chronic constipation. Normal portion of the colon proximal to the aganglionic segment is dilated, resulting in a “transition zone.”

Risk INCREASED with Down syndrome. Explosive expulsion of feces (squirt sign)–> empty rectum on digital exam

Diagnosed by absence of ganglionic cells on rectal suction biopsy. Treatment: resection

Answer 16

Malrotation

Anomaly of midgut rotation during fetal development Ž improper positioning of bowel (small bowel clumped on the right side)

formation of fibrous bands (Ladd bands). Can lead to volvulus, duodenal obstruction.

Question 17

Volvulus

Twisting of portion of bowel around its mesentery; can lead to obstruction and infarction. Can occur throughout the GI tract. Midgut volvulus more common in infants and children. Sigmoid volvulus (coffee bean sign on x-ray)

more common in elderly.

Answer 17

Intussusception

Telescoping of proximal bowel segment into a distal segment, commonly at ileocecal junction.

Compromised blood supply –> intermittent abdominal pain often with “currant jelly” stools. Patient may draw legs to chest to ease pain. Exam may reveal sausageshaped mass. Ultrasound shows “target sign.” Often due to a lead point, but can be idiopathic.

Most common pathologic lead point is a Meckel diverticulum (children) or intraluminal mass/tumor (adults). Majority of cases occur in children; unusual in adults

May be associated with rotavirus vaccine, Henoch-Schönlein purpura, and recent viral infection (eg, adenovirus; Peyer patch hypertrophy creates lead point).

Question 18

Other intestinal disorders

Acute mesenteric ischemia

Chronic mesenteric ischemia

Colonic ischemia

Angiodysplasia

Adhesion

Ileus

Meconium ileus

Necrotizing enterocolitis

Answer 18

Acute mesenteric ischemia-Critical blockage of intestinal blood flow (often embolic occlusion of SMA) –> small bowel necrosis–>abdominal pain out of proportion to physical findings. May see red “currant jelly” stools.

Chronic mesenteric ischemia–>“Intestinal angina”: atherosclerosis of celiac artery, SMA, or IMA–> intestinal hypoperfusion–> postprandial epigastric pain–> food aversion and weight loss.

Colonic ischemia-Reduction in intestinal blood flow causes ischemia. Crampy abdominal pain followed by hematochezia. Commonly occurs at watershed areas (splenic flexure, distal colon). Typically affects elderly. Thumbprint sign on imaging due to mucosal edema/hemorrhage.

Angiodysplasia-Tortuous dilation of vessels–>hematochezia. Most often found in the right-sided colon. More common in older patients. Confirmed by angiography. Associated with aortic stenosis and von Willebrand disease.

Question 19

Adhesion-Fibrous band of scar tissue; commonly forms after surgery. Most common cause of small bowel obstruction, demonstrated by multiple dilated small bowel loops on x-ray

Ileus-Intestinal hypomotility without obstruction–>constipation and decreased flatus; distended/tympanic abdomen with decreased bowel sounds. Associated with abdominal surgeries, opiates, hypokalemia, sepsis. Treatment: bowel rest, electrolyte correction, cholinergic drugs (stimulate intestinal motility).

Meconium ileus-In cystic fibrosis, meconium plug obstructs intestine, preventing stool passage at birth.

Answer 19

Necrotizing enterocolitis-Seen in premature, formula-fed infants with immature immune system. Necrosis of intestinal mucosa (primarily colonic) with possible perforation, which can lead to pneumatosis intestinalis, free air in abdomen, portal venous gas.

Colonic polyps-Growths of tissue within the colon. May be neoplastic or non-neoplastic. Grossly characterized as flat, sessile, or pedunculated (on a stalk) on the basis of protrusion into colonic lumen. Generally classified by histologic type.

Question 20

Malignant potential

Adenomatous polyps-Neoplastic, via chromosomal instability pathway with mutations in APC and KRAS. Tubular histology has less malignant potential than villous (“villous histology is villainous”); tubulovillous has intermediate malignant potential. Usually asymptomatic; may present with occult bleeding.

Answer 20

Serrated polyps-Premalignant. Characterized by CpG island methylator phenotype (CIMP; cytosine base followed by guanine, linked by a phosphodiester bond). Defect may silence MMR gene (DNA mismatch repair) expression. Mutations lead to microsatellite instability and mutations in BRAF. “Sawtooth” pattern of crypts on biopsy. Up to 20% of cases of sporadic CRC.

Question 21

Polyposis syndromes

Familial adenomatous polyposis-Autosomal dominant mutation of APC tumor suppressor gene on chromosome 5q21. 2-hit hypothesis. Thousands of polyps arise starting after puberty; pancolonic; always involves rectum. Prophylactic colectomy or else 100% progress to CRC.

Gardner syndrome-FAP + osseous and soft tissue tumors, congenital hypertrophy of retinal pigment epithelium, impacted/supernumerary teeth.

Answer 21

Turcot syndrome-FAP/Lynch syndrome + malignant CNS tumor (eg, medulloblastoma, glioma). Turcot = Turban

Peutz-Jeghers syndrome-Autosomal dominant syndrome featuring numerous hamartomas throughout GI tract, along with hyperpigmented mouth, lips, hands, genitalia. Associated with increased risk of breast and GI cancers (eg, colorectal, stomach, small bowel, pancreatic).

Juvenile polyposis syndrome-Autosomal dominant syndrome in children (typically < 5 years old) featuring numerous hamartomatous polyps in the colon, stomach, small bowel. Associated with increased risk of CRC.

Question 22

Lynch syndrome

Previously known as hereditary nonpolyposis colorectal cancer (HNPCC). Autosomal dominant mutation of DNA mismatch repair genes with subsequent microsatellite instability. ∼ 80% progress to CRC. Proximal colon is always involved. Associated with endometrial, ovarian, and skin cancers.

Answer 22

Colorectal cancer

EPIDEMIOLOGY Most patients are > 50 years old. ~ 25% have a family history

RISK FACTORS Adenomatous and serrated polyps, familial cancer syndromes, IBD, tobacco use, diet of processed meat with low fiber

PRESENTATION Rectosigmoid > ascending > descending.

Ascending—exophytic mass, iron deficiency anemia, weight loss.

Descending—infiltrating mass, partial obstruction, colicky pain, hematochezia.

Rarely, presents with S bovis (gallolyticus) bacteremia

Right side bleeds; left side obstructs (narrower lumen).

Diagnosis

Iron deficiency anemia in males (especially > 50 years old) and postmenopausal females raises suspicion

Screen low-risk patients starting at age 50 with colonoscopy ; alternatives include flexible sigmoidoscopy, fecal occult blood testing (FOBT), fecal immunochemical testing (FIT), and CT colonography. Patients with a first-degree relative who has colon cancer should be screened via colonoscopy at age 40, or starting 10 years prior to their relative’s presentation. Patients with IBD have a distinct screening protocol.

Apple core” lesion seen on barium enema x-ray

CEA tumor marker: good for monitoring recurrence, should not be used for screening.

Question 23

Molecular pathogenesis of colorectal cancer

Chromosomal instability pathway: mutations in APC cause FAP and most sporadic CRC (via adenoma-carcinoma sequence; (firing order of events is AK-53).

Microsatellite instability pathway: mutations or methylation of mismatch repair genes (eg, MLH1) cause Lynch syndrome and some sporadic CRC (via serrated polyp pathway).

Overexpression of COX-2 has been linked to colorectal cancer, NSAIDs may be chemopreventive

Answer 23

Cirrhosis and portal hypertension

Cirrhosis—diffuse bridging fibrosis (via stellate cells) and regenerative nodules (red arrows in A ; white arrows show splenomegaly) disrupt normal architecture of liver; increased risk for hepatocellular carcinoma (HCC). Etiologies include alcohol, nonalcoholic steatohepatitis, chronic viral hepatitis, autoimmune hepatitis, biliary disease, genetic/metabolic disorders.

Portal hypertension—increased pressure in portal venous system. Etiologies include cirrhosis (most common cause in Western countries), vascular obstruction (eg, portal vein thrombosis, BuddChiari syndrome), schistosomiasis

Spontaneous bacterial peritonitis-Also known as 1° bacterial peritonitis. Common and potentially fatal bacterial infection in patients with cirrhosis and ascites. Often asymptomatic, but can cause fevers, chills, abdominal pain, ileus, or worsening encephalopathy. Commonly caused by aerobic gram ⊝ organisms (eg, E coli, Klebsiella) or less commonly gram ⊕ Streptococcus

Diagnosis: paracentesis with ascitic fluid absolute neutrophil count (ANC) > 250 cells/mm3. Empiric first-line treatment is 3rd generation cephalosporin (eg, cefotaxime).

Question 24

Serum markers of liver pathology

Aspartate aminotransferase and alanine aminotransferase

increased in most liver disease: ALT > AST increased in alcoholic liver disease: AST > ALT

AST > ALT in nonalcoholic liver disease suggests progression to advanced fibrosis or cirrhosis

Answer 24

Alkaline phosphatase-increased in cholestasis (eg, biliary obstruction), infiltrative disorders, bone disease

γ-glutamyl transpeptidase-increased in various liver and biliary diseases (just as ALP can), but not in bone disease; associated with alcohol use

Question 25

FUNCTIONAL LIVER MARKER

Bilirubin increased in various liver diseases (eg, biliary obstruction, alcoholic or viral hepatitis, cirrhosis), hemolysis

albumin decreased in advanced liver disease (marker of liver’s biosynthetic function)

Prothrombin time increased in advanced liver disease (decreased production of clotting factors, thereby measuring the liver’s biosynthetic function)

Platelets decreased in advanced liver disease (decreased thrombopoietin, liver sequestration) and portal hypertension (splenomegaly/splenic sequestration)

Answer 25

Reye syndrome

Rare, often fatal childhood hepatic encephalopathy. Findings: mitochondrial abnormalities, fatty liver (microvesicular fatty change), hypoglycemia, vomiting, hepatomegaly, coma. Associated with viral infection (especially VZV and influenza) that has been treated with aspirin.

Mechanism: aspirin metabolites decreased β-oxidation by reversible inhibition of mitochondrial enzymes. Avoid aspirin in children, except in those with Kawasaki disease.

Steatosis of liver/hepatocytes

Hypoglycemia/Hepatomegaly

Infection (VZV, influenza)

Not awake (coma)

Encephalopathy

SHINE

Question 26

Alcoholic liver disease

Hepatic steatosis Macrovesicular fatty change that may be reversible with alcohol cessation.

Alcoholic hepatitis Requires sustained, long-term consumption. Swollen and necrotic hepatocytes with neutrophilic infiltration. Mallory bodies (intracytoplasmic eosinophilic inclusions of damaged keratin filaments).

Make a toAST with alcohol: AST > ALT (ratio usually > 2:1).

Alcoholic cirrhosis-Final and usually irreversible form. Sclerosis around central vein may be seen in early disease. Regenerative nodules surrounded by fibrous bands in response to chronic liver injury –> portal hypertension and end-stage liver disease.

Answer 26

Nonalcoholic fatty liver disease

Metabolic syndrome (insulin resistance); obesity–> fatty infiltration of hepatocytes–>cellular “ballooning” and eventual necrosis. May cause cirrhosis and HCC. Independent of alcohol use.

ALT > AST (Lipids)

Question 27

Hepatic encephalopathy

irrhosis –> portosystemic shunts –> decreased NH3 metabolism –> neuropsychiatric dysfunction. Reversible neuropsychiatric dysfunction ranging from disorientation/asterixis (mild) to difficult arousal or coma (severe).

Triggers:

ƒ increased NH3 production and absorption (due to dietary protein, GI bleed, constipation, infection).

ƒ decreased NH3 removal (due to renal failure, diuretics, bypassed hepatic blood flow post-TIPS)

Treatment: lactulose (increased NH4 + generation) and rifaximin or neomycin ( NH3 producing gut bacteria).

Answer 27

Hepatocellular carcinoma/hepatoma

Most common 1° malignant tumor of liver in adults.

Associated with HBV (+/− cirrhosis) and all other causes of cirrhosis (including HCV, alcoholic and nonalcoholic fatty liver disease, autoimmune disease, hemochromatosis, α1-antitrypsin deficiency) and specific carcinogens (eg, aflatoxin from Aspergillus). May lead to Budd-Chiari syndrome.

Findings: jaundice, tender hepatomegaly, ascites, polycythemia, anorexia. Spreads hematogenously

Diagnosis: increased α-fetoprotein; ultrasound or contrast CT/MRI, biopsy

Question 28

Other liver tumors

Cavernous hemangioma-Most common benign liver tumor; typically occurs at age 30–50 years. Biopsy contraindicated because of risk of hemorrhage.

Hepatic adenoma-Rare, benign liver tumor, often related to oral contraceptive or anabolic steroid use; may regress spontaneously or rupture (abdominal pain and shock).

Angiosarcoma-Malignant tumor of endothelial origin; associated with exposure to arsenic, vinyl chloride.

Metastases-GI malignancies, breast and lung cancer. Most common overall; metastases are rarely solitary

Question 29

Budd-Chiari syndrome-GI malignancies, breast and lung cancer. Most common overall; metastases are rarely solitary

Answer 29

α1-antitrypsin deficiency-Misfolded gene product protein aggregates in hepatocellular ER –> cirrhosis with PAS ⊕ globules in liver.

Codominant trait.

Often presents in young patients with liver damage and dyspnea without a history of smoking.

In lungs, decreased α1-antitrypsin –> uninhibited elastase in alveoli–> decreased elastic tissue–>panacinar emphysema.

Question 30

Jaundice

Abnormal yellowing of the skin and/or sclera due to bilirubin deposition. Hyperbilirubinemia 2° to increased production or decreased disposition (impaired hepatic uptake, conjugation, excretion).

HOT Liver—common causes of increased bilirubin level:

‘Hemolysis

Obstruction

Tumor Liver disease

Answer 30

Unconjugated (indirect) hyperbilirubinemia-Hemolytic, physiologic (newborns), Crigler-Najjar, Gilbert syndrome.

Conjugated (direct) hyperbilirubinemia-Biliary tract obstruction: gallstones, cholangiocarcinoma, pancreatic or liver cancer, liver fluke. Biliary tract disease:

ƒ 1° sclerosing cholangitis

ƒ 1° biliary cholangitis

Excretion defect: Dubin-Johnson syndrome, Rotor syndrome.

Mixed (direct and indirect) hyperbilirubinemia-Hepatitis, cirrhosis.

Question 31

Physiologic neonatal jaundice

At birth, immature UDP-glucuronosyltransferase –> unconjugated hyperbilirubinemia –> jaundice/ kernicterus (deposition of unconjugated, lipid-soluble bilirubin in the brain, particularly basal ganglia).

Occurs after first 24 hours of life and usually resolves without treatment in 1–2 weeks. Treatment: phototherapy (non-UV) isomerizes unconjugated bilirubin to water-soluble form.

Answer 31

Hereditary hyperbilirubinemias-All autosomal recessive.

Gilbert syndrome

Crigler-Najjar syndrome, type I

Dubin-Johnson syndrome

Rotor syndrome

Question 32

Gilbert syndrome-Mildly decrease UDP-glucuronosyltransferase conjugation and impaired bilirubin uptake. Asymptomatic or mild jaundice usually with stress, illness, or fasting. increased unconjugated bilirubin without overt hemolysis.

Relatively common, benign condition. Go! (asymptomatic/benign)

Crigler-Najjar syndrome, type I-Absent UDP-glucuronosyltransferase. Presents early in life; patients die within a few years. Findings: jaundice, kernicterus (bilirubin deposition in brain), increased unconjugated bilirubin. Treatment: plasmapheresis and phototherapy. Liver transplant is curative

Type II is less severe and responds to phenobarbital, which increased liver enzyme synthesis. No-go! (symptomatic)

Answer 32

Dubin-Johnson syndrome-Conjugated hyperbilirubinemia due to defective liver excretion. Grossly black (Dark) liver. Benign.

Rotor syndrome-is similar, but milder in presentation without black (Regular) liver. Due to impaired hepatic uptake and excretion.

Question 33

Wilson disease (hepatolenticular degeneration)

Autosomal recessive mutations in hepatocyte copper-transporting ATPase (ATP7B gene; chromosome 13) –> decreased copper incorporation into apoceruloplasmin and excretion into bile –> decreased serum ceruloplasmin.

Copper accumulates, especially in liver, brain, cornea, kidneys; increased urine copper.

Presents before age 40 with liver disease (eg, hepatitis, acute liver failure, cirrhosis), neurologic disease (eg, dysarthria, dystonia, tremor, parkinsonism), psychiatric disease, Kayser-Fleischer rings (deposits in Descemet membrane of cornea), hemolytic anemia, renal disease (eg, Fanconi syndrome).

Treatment: chelation with penicillamine or trientine, oral zinc.

Answer 33

Hemochromatosis-

Autosomal recessive. C282Y mutation > H63D mutation on HFE gene, located on chromosome 6; associated with HLA-A3. Leads to abnormal iron sensing and increase intestinal absorption (increase ferritin, increase iron, decrease TIBC –> increased transferrin saturation). Iron overload can also be 2° to chronic transfusion therapy (eg, β-thalassemia major). Iron accumulates, especially in liver, pancreas, skin, heart, pituitary, joints. Hemosiderin (iron) can be identified on liver MRI or biopsy with Prussian blue stain

Presents after age 40 when total body iron > 20 g; iron loss through menstruation slows progression in women.

Classic triad of cirrhosis, diabetes mellitus, skin pigmentation (“bronze diabetes”). Also causes restrictive cardiomyopathy (classic) or dilated cardiomyopathy (reversible), hypogonadism, arthropathy (calcium pyrophosphate deposition; especially metacarpophalangeal joints). HCC is common cause of death.

Treatment: repeated phlebotomy, chelation with deferasirox, deferoxamine, oral deferiprone.

Question 34

Biliary tract disease-May present with pruritus, jaundice, dark urine, light-colored stool, hepatosplenomegaly. Typically with cholestatic pattern of LFTs (increased conjugated bilirubin, increased cholesterol, increased ALP)

Primary sclerosing cholangitis

pathology

Unknown cause of concentric “onion skin” bile duct fibrosis Ž alternating strictures and dilation with “beading” of intra- and extrahepatic bile ducts on ERCP, magnetic resonance cholangiopancreatography (MRCP).

Epidemiology

Classically in middle-aged men with IBD.

Additional feature

Associated with ulcerative colitis. p-ANCA ⊕.  IgM. Can lead to 2° biliary cholangitis.  risk of cholangiocarcinoma and gallbladder cancer.

Primary biliary cholangitis

pathology: Autoimmune reaction –> lymphocytic infiltrate + granulomas –> destruction of lobular bile ducts

Epidemiology: Classically in middle-aged women.

Additional: Anti-mitochondrial antibody ⊕, increased IgM. Associated with other autoimmune conditions (eg, Sjögren syndrome, Hashimoto thyroiditis, CREST, rheumatoid arthritis, celiac disease)

Answer 34

Secondary biliary cholangitis

Extrahepatic biliary obstruction –> increased pressure in intrahepatic ducts –> injury/ fibrosis and bile stasis

Epidemiology: Patients with known obstructive lesions (gallstones, biliary strictures, pancreatic carcinoma).

Additional features: May be complicated by ascending cholangitis

Question 35

Gallstones (cholelithiasis)

increased cholesterol and/or bilirubin, decreased bile salts, and gallbladder stasis all cause stones.

2 types of stones:

ƒ Cholesterol stones (radiolucent with 10–20% opaque due to calcifications)—80% of stones. Associated with obesity, Crohn disease, advanced age, estrogen therapy, multiparity, rapid weight loss, Native American origin.

ƒ Pigment stones (black = radiopaque, Ca2+ bilirubinate, hemolysis; brown = radiolucent, infection). Associated with Crohn disease, chronic hemolysis, alcoholic cirrhosis, advanced age, biliary infections, total parenteral nutrition (TPN)

Answer 35

Risk factors (4 F’s):

1. Female
2. Fat
3. Fertile (multiparity)
4. Forty

Most common complication is cholecystitis; can also cause acute pancreatitis, ascending cholangitis. Diagnose with ultrasound.

Treat with elective cholecystectomy if symptomatic

Question 36

Biliary colic-Associated with nausea/vomiting and dull RUQ pain. Neurohormonal activation (eg, by CCK after a fatty meal) triggers contraction of gallbladder, forcing stone into cystic duct. Labs are normal, ultrasound shows cholelithiasis.

Choledocholithiasis-Presence of gallstone(s) in common bile duct, often leading to elevated ALP, GGT, direct bilirubin, and/or AST/ALT.

Answer 36

Cholecystitis

-Acute or chronic inflammation of gallbladder.

Calculous cholecystitis—most common type; due to gallstone impaction in the cystic duct resulting in inflammation and gallbladder wall thickening (arrows in B ); can produce 2° infection

Acalculous cholecystitis-—due to gallbladder stasis, hypoperfusion, or infection (CMV); seen in critically ill patients. Murphy sign: inspiratory arrest on RUQ palpation due to pain. Pain may radiate to right shoulder (due to irritation of phrenic nerve). increased ALP if bile duct becomes involved (eg, ascending cholangitis).

Diagnose with ultrasound or cholescintigraphy (HIDA scan). Failure to visualize gallbladder on HIDA scan suggests obstruction.

Gallstone ileus—fistula between gallbladder and GI tract –> stone enters GI lumen –> obstructs at ileocecal valve (narrowest point); can see air in biliary tree (pneumobilia)

Question 37

Porcelain gallbladder-Calcified gallbladder due to chronic cholecystitis; usually found incidentally on imaging. Treatment: prophylactic cholecystectomy due to high rates of gallbladder cancer (mostly adenocarcinoma).

Answer 37

Ascending cholangitis-Infection of biliary tree usually due to obstruction that leads to stasis/bacterial overgrowth. Charcot triad of cholangitis includes jaundice, fever, RUQ pain. Reynolds pentad is Charcot triad plus altered mental status and shock (hypotension)

Question 38

Acute pancreatitis-Autodigestion of pancreas by pancreatic enzymes ( A shows pancreas [yellow arrows] surrounded by edema

Causes:

Idiopathic,

Gallstones,

Ethanol,

Trauma,

Steroids,

Mumps,

Autoimmune disease,

Scorpion sting,

Hypercalcemia/Hypertriglyceridemia (> 1000 mg/dL),

ERCP, Drugs (eg, sulfa drugs, NRTIs, protease inhibitors).

I GET SMASHED.

Diagnosis by 2 of 3 criteria:

acute epigastric pain often radiating to the back,

increased serum amylase or lipase (more specific) to 3× upper limit of normal,

or characteristic imaging findings.

Complications: pseudocyst B (lined by granulation tissue, not epithelium), abscess, necrosis, hemorrhage, infection, organ failure (ARDS, shock, renal failure), hypocalcemia (precipitation of Ca2+ soaps).

Answer 38

Pancreatic adenocarcinoma

Very aggressive tumor arising from pancreatic ducts (disorganized glandular structure with cellular infiltration A ); often metastatic at presentation, with average survival ~ 1 year after diagnosis. Tumors more common in pancreatic head B (–> obstructive jaundice). Associated with CA 19-9 tumor marker (also CEA, less specific).

Risk factors:

ƒ Tobacco use

ƒ Chronic pancreatitis (especially > 20 years)

ƒ Diabetes ƒ Age > 50 years

ƒ Jewish and African-American males

Often presents with:

ƒ Abdominal pain radiating to back

ƒ Weight loss (due to malabsorption and anorexia)

ƒ Migratory thrombophlebitis—redness and tenderness on palpation of extremities (Trousseau syndrome)

ƒ Obstructive jaundice with palpable, nontender gallbladder (Courvoisier sign)

Treatment: Whipple procedure, chemotherapy, radiation therapy.