GI path Flashcards

Question

A 30 year old man comes into the office complaining of alterations in his bowel habits- he has abdominal pain relieved by defecation and constipation followed by diarrhea. Based on the examinaiton of his anus below as well as his symptoms, what might his diagnosis be?

Answer 1

**Irritable bowel disease**: can also see **Elephant ears** (below). Generally due to **Crohn Disease** Also at risk for developing enteroenteric fistula

Answer 2

Diverticulitis _Symptoms_: Abdominal pain (**Left distal colon**), constipation, fever - **Common cause of hematochezia** (older person losing lots of blood per rectum!) _Etiology_: Very common in **elderly** (incidence correlates with age) - Poorly understood but is related to intestinal motility, colonic structure, diet and genetics - Low residue/ low fiber diet - May be related to **muscular hypertrophy of the colon and increased intraluminal pressure** (created by pulsion) - Prolonged colonic transit, decreased fecal fiber _Progression:_ - Symptomatic uncomplicated disease - Recurrent symptomatic disease - Complicated disease - Hemorrhage, abscess, perforation, peritonitis, stricture, fistula _Natural history_ 80-85% asymptomatic 15-20% present with abdominal pain 1-2% will require hospitalization 0.5% will require surgery _Treatment_ - Surgery - IV antibiotics - Oral antibiotics - Low fiber diet - 50-70% of patients with one event will not have another event - Then high fiber diet in 6-8 weeks _Increased in:_ - Family history of diverticulitis - Complicated diverticulitis with retroperitoneal abscess - More than 5cm of colon involved in the initial episode

Answer 3

**Cirrhotic liver**: trichrome stains fibrosis blue - Chronic hepatitis/alcohol ingestion--\> cirrhosis - Only 3% of patients with cirrhosis decompensate each year

Answer 4

**Diffuse microvesicular steatosis**: rare, reflects hepatocellular injury and damage to mitochondria, beta-oxidation of fatty acids - See small lipid vacuoles (multiple) in hepatocytes - Can be seen in lysosomal storage diseases, toxicities to medications (Reye's)

Answer 5

**Hepatocellular carcinoma**: See pseudoglanular architecture, thickened cords of atypical hepatocytes, fibrotic tissue (cirrhosis from chronic Hep B) Seen in setting of cirrhosis- most common *primary* liver cancer Risk factors; - **Cirrhosis** (most important) - Underlying etiology for cirrhosis plays role: ex: **Hep C,** hep B (without cirrhosis) - Male \> female - 50% patients with HCC have markedly elevated alpha-fetoprotein **Histo**: nuclear atypia, **liver plates expanded** (10 cells thick vs 1-2 cells)--\> nested appearance (confirm with reticulin stain--\> expansion)

Answer 6

**Cavernous Hemangioma**= benign neoplasm comprised of blood vessels. **Most common benign liver tumor** Histo: Large, dilated vascular channels in fibrous tissue

Answer 7

**Hepatic adenoma**: associated with **OCP**, anabolic steroid use - **Benign** clonal proliferation of hepatocytes; arises in **non-cirrhotic liver** - Risk factors: diabetes, obesity, **females \>males** _Tumors often excised because_: - May rupture/bleed (**below)** - Reports of extremely rare malignant transformation - Diagnostic purposes (can't tell what it is in stiu) **Histo**: Thick-walled intra-lobular arteries with no portal tract; steatosis; no marked expansion of hepatic plates

Answer 8

**Venous outflow obstruction**: Seen in: - Right-sided heart failure - Budd-Chiari= acute/chronic obstruction of major hepatic veins due to thrombosis. Seen in myeloproliferative disorders, disorders of coagulation (antithrombin deficiencies, protein-S, Protein C, mutation in factor V), antiphospholipid syndrome, HCC * *Histo**: Venous outflow obstruction can lead to portal hypertension--\> causes dilation of Zone 3 sinusoids, can also see ischemic necrosis. - Red blood cells can be pushed into Space of Disse **Chronic outflow obstruction**--\> atrophy and fibrosis (**Below)**--\> called "cardiac cirrhosis/sclerosis" **Chronic passive congestion--\> nutmeg liver**[![]()](https://s3.amazonaws.com/brainscape-prod/system/cm/019/923/356/q_image_thumb.jpg?1360004129)

Answer 9

**Alpha-1-antitrypsin deficiency**: Alpha-1 antitrypsin is elastase inhibitor- autosomal co-dominant (PiZZ or PiMZ) defect causes misfolding--\> deficiency. Proteins get stuck in liver and cause damage: - Neonatal jaundice in 10% PiZZ - Adult presentation: chronic hepatitis, cirrhosis - Increased risk of HCC - Seen in 10-15% of PiZZ genotypes (mostly Europeans, Scandinavians) **Emphysema**: alpha-1 antitrypsin blocks elastase in lungs--\> excess lung tissue breakdown **Treatment**: Liver transplant cures disease **Histo**: globules stained with PAS and diastase (to eliminate glycogen staining)

Answer 10

Dublin-Johnson Pigment: dark brown-black "melanin-like" pigment seen in hepatocytes in **Dublin-Johnson** syndrome (autosomal recessive disorder causing increased _conjugated bilirubin_, grossly black liver--\> oral contraceptives and pregnancy can reveal underlying disorder due to jaundice) \*Rotor syndrome= similar to Dublin-Johnson without melanin-like dark pigment deposition in liver

Answer 11

**Wilson's disease**: Rare, autosomal recessive mutation in **ATP7B (**transmembrane copper-transporting ATPase) on **chromosome 13** Disorder of copper excretion through bile canaliculus--\> hamage liver through formation of ROS species in hepatocytes * *Natural history:** - Stage 1: Accumulation of copper in liver (latency) - Stage 2: Hepatic capacity exceeded--\> critical systemic illness (hemolysis at 6-50 years)--\> **hepatic encephalopathy (asterixis)** - Stage 3: Accumulation of copper in brain **(basal ganglia= putamen, caudate, globus pallidus--\> dementia, dyskinesia, dysarthria)**, **eye (corneal deposition),** other extrahepatic tissues - Stage 4: Chelation therapy to acheive copper balance, chelation therapy in some cases Symptoms: - **Kayser-Fleisher rings** - Neuropsychiatric disorders - Cardiomyopathy - **Hepatitis**, Cirrhosis - Fanconi syndrome - Hemolysis - Osteopenia, **arthropathy** Diagnosis: Ceruloplasmin (low)- \< 20 mg/dL **Slit lamp exam for Kayser-Fleisher rings** Urine copper \> 100 ug/ 24hr \*If positive for any of three above, liver biopsy with quantitative copper (250 microgram copper/ 1 g dried liver); Genetic testing for **ATP7B** mutations **Treatment**: Chelation of excess circulating copper - Trientine - D-penicillamine Zinc: diminishes copper absorption Liver transplantation is curative First degree relatives should be screened - ceruloplasmin level, slit-lamp examination

Answer 12

Hemochromatosis: Autosomal recessive mutation in **HFE (C282Y or H63D)**--\> defective hepcidin production in liver--\> no feedback inhibition of iron absorption in intestines--\> excess iron buildup - **HLA-A3 type - Total body iron may reach 50 g** - Progressive deposition in Zone 1---\> Zone 3 Clinical presentation: - Cirrhosis - Bronzing skin - Diabetes - Testicular atrophy - Conduction abnormalities in heart Diagnostic testing: **Genetic: GOLD standard** - Homozygous C282Y/C282Y (white Europeans) - Compound heterozygous C282Y/H63D (worldwide) Serum tests: - iron (high \> 175) - iron binding capacity (low \< 300) - transferrin saturation (high \> 50%) - ferritin levels (high \> 300) Radiographs: **T2 weighted MRI, lower than normal intensity signal in liver** Liver biopsy: - Stainable iron (prussian blue) - Hepatic iron index (\> 5600 compared to 1800) **Treatment:** Response to phlebotomy \*\* high risk of HCC (first degree relatives should be screened by transferrin saturation, ferritin)

Answer 13

PBC= Primary biliary cholangitis; **serum anti-mitochondrial antibodies** (autoimmune reaction--\> lymphocytes and granulomas; destruction of intrahepatic ducts, cholestasis - Associated with **CREST, RA, celiac, Sjogren's** Female Early signs: - Asymptomatic with elevated alkaline phosphatase (out of proportion to bilirubin) **- Pruritis without Jaundice** - Malabsorption of fat-soluble vitamin ( can lead to elevated INR in absence of end-stage liver disease due to decreased Vit K absorption) Later signs: - Xanthomas - Osteoporosis (Vit D malabsorption) - Jaundice, ascites, portal HTN (liver failure) Treatment: 1, Ursodeoxycholic acid (Ursodiol) - replaces hepatotoxic bile salts - Symptomatic/biochemical improvement - transplant-free survival advantage 2. Cholestyramine - Binds bile acids, can relieve pruritis - No effect on natural history of disease 3. Liver transplantation (curative but can RECUR) Testing: 1. Elevated Alkaline phosphatase 2. Ultrasound of liver/gallbladder (look for obstruction) 3. **AMA blood test** 4. Liver biopsy Labs: - AMA (antimitochondrial antibodies)- 90% - Elevated Alkaline phosphatase without liver failure * *Histo**: - Involves intrahepatic bile ducts (MICROscopic) - See bile duct lesions (lymphocytic infiltration/granulomatous inflammation) - Chronic non-suppurative destruction cholangitis - Leads to ductopenia/fibrosis

Answer 14

* *Onion skin fibrosis**= intrahepatic duct involvement in **primary sclerosing cholangitis**. - Strictures and dilation--\> **beading of intra- and extra-hepatic ducts on ERCP** Associated with hypergammaglobulinemia, Ulcerative colitis - can lead to secondary biliary cirrhosis **below**: fibrosis causing ductopenia PSC features: - Rule of 7s: 70% male, 70% associted with Ulcerative Colitis (rare Crohn association), 7% develop **cholangiocarcinoma** - Pruritis - Jaundice - Fever due to ascending cholangitis - Increased Alk Phos - Atypical P-ANCA (reaction with nuclear envelope proteins of neutrophils) - Involves extrahepatic/hilar (large) bile ducts; may involve intrahepatic ducts - Histologic features: onion skin fibrosis (small duct involvement), ductopenia, fibrosis * *- Beading on cholangiography**

Answer 15

**Cholesterol gallstones** Risk factors: (female, fat, fertile, forty) - Reproductive age women (estrogen) - Obesity - Oral contraceptives - Genetics (Pima indians) - Diet/metabolic abnormalities (cholesterol) - Drugs (fibrates) Stones composed largely of cholesterol are radiolucent Sufficient calcium carbonate is found in10-20% of cholesterol stones to render them radiopaque

Answer 16

**Black pigmented stones** due to unconjugated hyperbilirubinemia. This patient exhibits signs of either **hemolytic anemia or a thalassemia**, which cause to an excess of bilirubin that the liver is unable to conjugate. This excess backs up in the gallbladder and forms black stones. Additionally she developed jaundice from the excess bilirubin levels. \* Brown pigmented stones= conjugated hyperbilirubinemia due to obstruction of duct _Causes of unconjugated hyperbilirubinemia:_ (Diagnosed if **more than 80% of an elevated total bilirubin is indirect**) Elevation results from either: 1. Increased bilirubin production - **Hemolytic anemia (bilirubin rarely \> 4 mg/dL)** - Hematoma - **Ineffective erythropoiesis (thalassemia, pernicious anemia)** - Neonatal (physiologic) jaundice 2. Reduced hepatic ability to conjugate bilirubin= Glucuronosyltransferase deficiency in: - Gilbert's syndrome (young men)= jaundice in times of stress/illness- not fatal - Crigler-Najjar syndrome (rare) - Neonatal (physiologic syndrome) **Imaging**: black stones contain high levels of calcium carbonate and phosphate--\> 50-75% radiopaque

Answer 17

**Acute cholecystitis**: diffuse inflammation of the gallbladder. 90-95% of cases associated with gallstones. - Acalculus cholecystitis occurs in sepsis, severe trauma, **salomonella infections**, polyarteritis nodosa * *Gross pathology**: - Usually enlarged and tense, may assume a bright red or blotchy, violaceous to green-black discoloration, imparted by subserosal hemorrhages - The serosal covering is frequently layered by fibrin and, in severe cases, by suppurative exudate - The gallbladder lumen may contain stones, is filled with a cloudy or turbid bile that may contain large amounts of fibrin, pus, and hemorrhage - The gallbladder wall is thickened, edematous, and hyperemic. - Complication: Perforation (bile peritonitis) **Below**: cholecystitis with empyema Histo: acute inflammation, edema, hemorrhage, mucosal ulceration/widespread necrosis (gangrenous)

Answer 18

**Acute pancreatitis**: An inflammatory condition of the exocrine pancreas that results from injury to acinar cells and release of enzymes **Pancreatic pseudocyst=** lined by granulation tissue (not epithelium)- can rupture and hemorrhage Clinical presentation: - Attacks typically mild, but 20% very severe - An attack lasts for a short time and usually resolves completely - Severe cases lead to hemorrhagic pancreatitis with massive necrosis - **Abdominal pain, nausea, low-grade fever, dehydration** Etiologies: Metabolic: **alcoholism**, hyperlipoproteinemia, hypercalcemia, drugs Mechanical: **_gallstones_**, trauma, operative injury, endoscopic procedures Vascular: shock, atheroembolism, vasculitis Infectious: **mumps**, coxsackievirus **Genetic: mutations in cationic trypsinogen (PRSS1) and trypsin inhibitor (SPINK1)** Labs: elevated amylase (also in saliva) and lipase (more specific to pancreas) - Markers= CRP, TAP (trypsinogen activation peptide), MCP (monocyte chemotactic protein) Complications: - Lung: Phospholipase A2 released from pancreas--\> breaks down surfactant (ARD), subdiaphragmatic irritation causes restricted breathing - Kidney: vasoconstriction, hemorrhage--\> kidney damage - DIC: release of factors enhancing fibrinolysis and coagulation Imaging: - CT= imaging modality of choice. Wait 72 hours before administering with contrast (rehydrate patient or dye could damage kidneys). - MRI= in pregnant patients Prognosis: 80% mild, 20% severe attacks (9% mortality) Treatment: supportive - Replenish fluids - Monitoring - Antibiotics ONLY if sign of infection - **Feed the gut**: insure gut immune functions continue Histo: see **fat saponification** (think like vegetable cells), calcification Morphology: (1) Edema caused by microvascular leakage (2) Fat necrosis by lipolytic enzymes (saponification) (3) Acute inflammation (4) Proteolytic destruction of pancreatic parenchyma (5) Destruction of blood vessels and subsequent interstitial hemorrhage

Answer 19

Normal gastro-esophageal (squamocolumnar) junction: Mucosal junction (gastroesophageal) and squamocolumnar tissue line up at Z-line \* In metaplasia (Barrett's)- Z line (mucosal junction) ABOVE columnar tissue

Answer 20

Esophageal atresia and tracheoesophageal fistula= Embryologic failure of tubal esophagus to connect mouth to stomach, ending in a blind pouch; fistula may connect segment to trachea (In **85% of cases, proximal esophagus is blind end, trachea attaches to distal esophagus**) Clinical picture: - 1/3000 live births - \* 50% have congenital anomalies: **VATER syndrome** (vertebral defects, anal atresia, trachoesophageal fistula, renal dysplasia) - See respiratory symptoms (aspiration pneumonia) Pathogenesis: most likely due to abnormal hedgehog signaling pathway

Answer 21

Histo: dysplasia in Barrett's esophagus BE without dysplasia= 2% cancer risk BE **with dysplasia**= 20% risk of cancer (high grade dysplasia) - 45% of low-grade dysplasias will progress to high grade

Answer 22

Congenital hypertrophic pyloric stenosis= Concentric enlargement of the pyloric sphincter and narrowing of the pyloric canal that obstructs the gastric outlet M:F 4:1 Mostly Caucasian; rare in blacks & Asians Possible genetic as well as environmental (drugs, infection in utero) pathogenesis Symptoms: - Emesis (non-bilious, projectile) in 3-6 weeks - Poor weight gain, dehydration (hypochloremic alkalosis) Diagnosis: palpate "olive", pyloric sonograms, UGI series Treatment: surgical: pyloromyotomy (open up pyloris muscle) **baby**: see palpable epigastric mass (olive) **gross path**: concentric hypertrophy, hyperplasia of pyloric muscularis propria

Answer 23

**Autoimmune gastritis**: Immune-mediated form of chronic gastritis--\> loss of parietal cells--\> hypo/achlorhydria, Vit B12 deficiency Autosomal dominant, seen in \< 5% chronic gastritis, F \> M, **accompanied by pernicious anemia** (megaloblastic anemia due to decreased B12 **Labs**: increased gastrin, decreased B12, positive Anti-parietal cell Ab, anti-intrinsic factor Ab **Histo**: only seen in **body/fundus** of stomach: lymphoplastic inflammation in deep, glandular lamina propria--\> loss of glands--\> atrophy--\> achlorhydria. Also see **intestinal metaplasia of goblet cells, ECL hyperplasia** (both are precursors to tumor formation: Intestinal metaplasia--\> 13-fold increased risk of gastric carcinoma; ECL cell hyperplasia--\> neuroendocrine tumors- 13-fold increase)

Answer 24

Colonic strictures: Caused by: chronic ischemia (fibrosis) Crohn Disease (increased muscle, propria hypertrophy, hyperplasia), malignancy, recurrent bouts of diverticulitis; NOT seen in UC

Answer 25

**Candida esophagitis:** pain with swallowing (odynophagia) due to severe inflammatory process disrupting esophageal mucosa Seen in: immunosuppressed, diabetics, recent antibiotic usage Histo: pseudohyphae

Answer 26

**CMV esophagitis**: pain with swallowing (*odynophagia)* due to severe inflammatory process disrupting esophageal mucosa Histo: Base of ulcer: see large intranuclear inclusion with granular cytoplasmic inclusions

Answer 27

**Peptic stricture**: due to recurrent damage from GERD can form scar tissue in esophagus--\> leads to achalasia (difficulty swallowing) - long history of heartburn and antacid use--\> symptoms remit as stricture develops Below: GERD-induced esophagitis leading to stricture formation

Answer 28

**Esophageal adenocarcinoma** - Hx of recent, but, progressive dysphagia, older pts - Irregular narrowing on barium swallow - Endoscopic biopsy and/or cytology required for diagnosis - Adenocarcinoma – arises in Barrett’s Esophagus \*Adenocarcinoma accounts for ~70% of esophageal cancers in USA

Answer 29

**Schatzki's ring**: - Thin mucosal invagination in distal esophagus at Gastro-esophageal junction - Asymptomatic ring in about 10% of normals - Intermittent dysphagia solids, persistent if \<1.2 cm. - Can be missed on barium swallow, so include solid bolus (marshmellow?) or endoscopy (EGD) Diagnosis: intermittent dysphagia for solids (lumen 1.2 cm- 2.0 cm). persistant dysphagia with lumen \< 1.2 cm

Answer 30

Scleroderma causing dysphagia: (80% of scleroderma pts) - **Weak LES**, low amplitude/nonexistant contractions of esophageal body Symptoms= heartburn, regurgitation; often associated with Raynaud's syndrome - Skin changes (**Scleroderma skin**): hardened, thickened skin on face, telangiectasia, sclerodactyly, calcinosis cutis (CREST syndrome)

Answer 31

**Diffuse esophageal spasm** - Intermittent dysphagia to solid and liquids - May cause severe chest pain (50% of non-MI chest pain cases in ER)- releved by nitroglycerin - Simultaneous (non-peristaltic) contractions, usually mixed with peristaltic contractions - Corkscew, step ladder, “rosary bead esophagus” Diagnosis= symptoms of dysphagia +/- chest pain plus esophageal manometric anomalies

Answer 32

**Eosinophilic esophagitis** Dysphagia for solid \> liquid foods More common in males, see history of allergen sensitivity - “Ringed” or “feline” esophagus on endoscopy - Dense eosinophilic infiltration (\> 20 /hpf on mucosal biopsy \* leading cause of solid food bolus impaction in general GI practice (\>50% of cases) **\* Eosinophilic esophagitis patients are highly susceptible to mucosal tearing (laceration) and transmural perforation during endoscopy, dilation procedures, bolus impaction and vomiting.** **Boerhaave's syndrome= Spontaneous rupture (seen with transmural infiltrate)** _Treatment_: - Elimination diets: Milk, eggs, soy, corn, wheat, beef, chicken - Oral Fluticasone: Flonase, Flovent - Steroids (Budesonide, Pednisone) - Singulair? - Chromalyn? - Gentle Esophageal Dilatation _only After Medical Trial_

Answer 33

**- Esophageal Squamous cell carcinoma:** Risk factors are heavy smoking and alcohol - See progressive dysphagia (initially only issues swallowing solid food) - May see: extreme weight loss, **irregular esophageal narrowing on Barium swallow (below**)

Answer 34

**Branched crypts in colon**: Early/non-specific IBD - Acute inflammatory cells, cryptitis/ crypt abscess - **Chronic IBD**: paneth cell metaplasia, crypt distortion, basal lymphoid aggregation, chronic inflammatory cells

Answer 35

Splenic flexure ischemia: only 1 blood source

Answer 36

Colon cancer

Answer 37

**C. Difficile** infection following hospitalizations/antibiotic course (must rule out **ischemia**, which has similar pseudomembrane) Cause= _Antibiotics_: Oral \> IV; Cephalosporins, PCNs, Clindamycin; Up to 8 wks after abx course _Treatment_ PO metronidazole 500mg TID x 10 days PO vancomycin 125mg QID x 10 days Expect response in 3 – 4 days, recurs in 12-24% Probiotics (florastar 250mg 2tabs PO BID) Handwashing \***Do NOT use anti-diarrheal (anti-motility) drugs**- this can exacerbate the condition as it leaves bacteria in colon longer to cause more toxin damage **Histo**: Pseudomembranes composed of fibrin, mucin, neutrophils. Glands lose epithelial cells (C. diff effects cells adhesion, while ischemia has hemosiderin laden macrophages)

Answer 38

Pancreatic acinar cells **Below:** Islet of Langerhaans

Answer 39

**Acute hemorrhagic pancreatitis**: - Abrupt onset following heavy meal/alcohol - Extensive tissue destruction with circulatory collapse and shock - Elevated serum amylase and lipase levels - 50% mortality - May develop pseudocyst (if survive)

Answer 40

**Chronic pancreatitis** - Recurrent, progressive pancreatic tissue destruction * *- Alcohol abuse** is a major cause - Chronic inflammation, fibrosis, calcification - Pancreatic insufficiency with malabsorption and/or diabetes - 3-4% mortality/year * *Clinical presentation:** - 50% of attacks are recurrent - Symptoms of Acute pancreatitis - Chronic pain / nausea: Constant, dull, radiates to back, worse with food - Malabsorption: Diarrhea, steatorrhea - Diabetes - Weight loss * *Alcholic pancreatitis:** - Direct acinar cell toxicity - Alters membrane infrastructure--\> increased permeability - Increased basal protein secretion - Decreases trypsin inhibitor - Alters lithostatin--\> precipitation of Ca - Decreased endocrine function * *Diagnosis: 1. MRI/MRCP= GOLD standard** - Shows parenchymal fibrosis, ductal abnormalities 2. CT: irregular contour, calcifications, dilated duct, cysts 3. Endoscopic ultrasound 4. Plain X-ray film: shows calcifications * *Complications**: - Narcotic addiiction - Malnutrition - Pseudocyst formation - Common bile duct obstruction - Duodenal obstruction - Splenic vein thrombosis--\> gastric varices (bleeding complications)

Answer 41

**Autoimmune pancreatitis, lymphoplastic clerosing type** - Seen in 4th to 6th decade - Associate with autoimmune conditions (primary sclerosing cholangitis, Sjogren, etc.) - Some with “multifocal inflammatory fibrosclerosis” (Riedel thyroiditis, orbital pseudotumor, mediastinal and retroperitoneal fibrosis, etc.) - Mimicks pancreatic carcinoma both clinically (obstructive jaundice) and radiologically (mass-like lesion); “sausage-like” appearance on imaging - Some with elevated serum IgG4 levels (usually \>135 mg/dl) - Respond well to steroid administration **Histo:** - See duct-centric inflammation (lymphoplasmacytic cells), periductal fibrosis, periphlebitis, venule obliteration, interstitial fibroblast proliferation - IgG4-positive plasma cells

Answer 42

**Pseudocysts** complications of _chronic pancreatitis_, not true cyst (no epithelial lining)

Answer 43

**Pancreatic ductal carcinoma**: 85% of pancreatic cancers Symptoms: - Anorexia - Weight loss - Abdominal/back pain - Jaundice - Migratory thrombophlebitis (Trousseau’s sign) hypercoagulability and tendency to venous thrombosis * *Ductal adenocarcinoma**: - Derived from ductal cells--\> Spreads by direct extension along nerves and lymphatic spread - Significant cause of cancer deaths: 4th in men, 5th in women * *- Only 20% of PDA patients are surgical candidates; of these only 5% will survive 5 years - Overall 5 year survival is 5%** Most lethal of all of the solid malignancies Highest incidence after age 60 Risk factors: - Smoking - Chemical exposure - High meat/fat diet - Diabetes - Chronic pancreatitis \* Approximately 10% familial Somatic genetic changes in pancreatic carcinoma: - 90% KRAS activating mutations - 95% P16 deletion - 70% TP53 mutation - 55% SMAD4 mutation/deletion Below: See **perineural invasion**

Answer 44

**Serous cystadenoma** 3:1 female predominance, and **Von Hippel Lindau** patients are at increased risk for its development Symptoms are often nonspecific Almost always benign, and surgical resection is curative in the vast majority of patients Composed of glycogen-rich cuboidal cells surrounding small (1 to 3 mm) cysts containing clear, thin, straw-colored fluid

Answer 45

**Mucinous cystic neoplasm** 95% arise in women **1/3 associated with invasive cancer** Body or tail of the pancreas Painless, slow-growing mass The cysts are lined by columnar mucinous epithelium, and a dense **ovarian-type stroma** Not involving the major pancreatic duct

Answer 46

**Intraductal papillary mucinous neoplasm (IPMN)** - Precursor lesion to Pancreatic ductal adenocarcinoma - More common in men - Can be multifocal - Involving the main pancreatic duct or its major branches - Lack of ovarian type stroma - 5 year survival: IPMN: 90-100% IPMN with associated invasive carcinoma: 40%

Answer 47

**Solid pseudopapillary neoplasm**: - Low grade malignant neoplasm - Affects young women - Symptoms of intra-abdominal mass, often palpable on clinical exam - 30% discovered incidentally - 10-15% of patients will develop metastasis or recurrence; most of these are resectable and patients survive long time - **Mutation of beta catenin gene**- can see on histo stain

Answer 48

**Pancreatoblastoma** **Most common pancreatic tumor in children Adults have mean survival of 18 months Microscopically shows acini and squamoid corpuscle**

Answer 49

**Pancreatic neuroendocrine tumor- insulinoma** - Derived from islet cells - May be non-functional or functional (symptoms relate to hormone produced) - 5% of clinically detected pancreatic neoplasms - Males and females are equally affected - Most occur between 30 and 60 yrs; those arising in patients with multiple endocrine neoplasia 1 (MEN1) syndrome occur at a younger age **Insulinoma**: Derived from beta cells, most common pancreatic islet cell tumor (75%) - Excess secretion of insulin (hypoglycemia, sweating, nervousness, hunger, confusion, lethargy) - Most are benign, solitary, small (75% \< 2 cm) - **Histo: stain for insulin: Uniform nests of cells, richly vascular, amyloid deposition**

Answer 50

Normal gallbladder histo: - Notice only ONE layer of smooth muscle (vs remainder of GI tract, with two layers: muscularis mucosae and muscularis externa

Answer 51

**Chronic cholecystitis** Persistent inflammation of gallbladder **\>90% associated with gallstones** Gallbladder has thickened and fibrotic wall **Histo: Rokitansky-Aschoff sinuses** Below: X-ray image showing **porcelain gallbladder**: calcification of the gallbladder resulting from chronic cholecystitis. **Note**: patients with porcelain gallbladder are at increased risk of cancer of the gallbladder\* \* Brown stones in intra-hepatic/extra-hepatic bile ducts can be due to ascending infection--\> bacteria unconjugates bilirubin

Answer 52

Cholesterolosis= "Strawberry gallbladder": **due to excess cholesterol within gallbladde**r. Mucosa takes on "stippled" appearance (like a strawberry) due to excess fat uptake from mucosal cells [![]()](https://s3.amazonaws.com/brainscape-prod/system/cm/019/129/324/a_image_thumb.jpg?1359660122)

Answer 53

**Gallbladder adenocarcinoma**: - More common in females (females:males 3–4:1) - \>90% aged ≥50 years at diagnosis - Right upper quadrant abdominal pain, anorexia * *- Metastatic disease in ≈50% at surgery** - Gross pathology: diffuse wall thickening or polypoid growth - Histology: adenocarcinoma showing varying degree of differentiation * *- 5-year survival rate: \>90% for stages I and II, 11% for stages III and IV** **Risk factors: cholelithiasis, chronic cholecystitis**

Answer 54

Prussian blue stain of hepatocytes: stains for iron (predominantly in **zone 1**) - Chunky, golden-brown cytoplasmic pigment Excessive iron= toxic to host tissues. Causes lipid peroxidation, stimulation of collagen (activates hepatic stellate cells), disrupts DNA--\> apoptosis, hepatocellular carcinoma (HCC). No significant inflammation due to direct toxicity Iron accumulation in: - Hepatocytes= hereditary hemochromatosis - Kupffer cells= secondary to blood transfusions, ineffective erythropoiesis (thalassemia) - Mild accumulation in both hepatocytes and Kupffer cells= chronic liver disease (steatohepatitis, cirrhosis, HCV) - Bile ducts Accumulation can also be due to low levels of hepcidin (main regulator of iron absorption- decreases intestinal absorption)

Answer 55

Bile pigment (bilirubin): seen in canalicular space between hepatocytes (can also accumulate within hepatocytes/ Kupffer cells). Located primarily in **Zone 3** - Heme breakdown--\> billirubin--\> bile pigment - Accumulation= cholestasis, bilirubinostasis

Answer 56

Lipofuscin= finely granular, light yellow-brown cytoplasmic pigment. **Zone 3** - "Wear and tear" pigment associated with _aging and drugs_ - NOT injurious to cell/functions, but demonstrates previous injury due to free radicals and lipid peroxidation

Answer 57

Macrovascular steatosis= abnormal accumulation of triglycerides in hepatocytes. Most common in alcohol abuse and non-alcoholic fatty liver disease (food abuse) \*Reversible cell damage **Below**: Liver diffusely yellow due to fat accumulation. Due to alcohol abuse, non-alcoholic fatty liver disease, viral hepatitis C, drugs VS: steatohepatitis= fatty liver with **lobular inflammation** and injury (due to ASH, NASH). See neutrophilic/lymphocytic inflammation, cellular swelling (ballooning), Mallory bodies

Answer 58

Hepatocellular swelling: liver cells unable to maintain homeostasis due to: - Acute hepatitis, severe flare of chronic hepatitis - Cholate stasis (feathery degeneration due to bile salt accumulation) - Steatohepatitis "balloon cells" (fatty and fibrotic changes) Histo: swelling, vacuolization/lightening of cytoplasm, clumping intermediate filaments, cell membrane blebbing (unlike vacuolization of fat in steatosis) \***Reversible cell damage**

Answer 59

Apoptotic hepatocytes: spotty necrosis, **councilman body** (only in the context of **yellow fever)**, acidophilic body= eosinophilic globule in liver - SINGLE acidophilic cells= apoptosis (vs clusters= necrosis)

Answer 60

Hepatic necrosis= clusters of dead hepatocytes due to ischemia, drug-dependent injury

Answer 61

Kupffer Cells= hepatic macrophages, clean up damage (any type) in hepatocytes. Grayish tinge (**ceroid**)= pigment accumulating in macrophages similar to lipofuscin ("wear and tear") due to peroxidation of lipids

Answer 62

**Portal tract inflammation**= typical of chronic hepatitis - Mildly active (low levels of interface inflammation- as opposed to **interface inflammation** in image below) Due to Hepatitis B (+/- Hep D), **hepatitis C**, or autoimmune hepatitis - Other causes= drug reaction, Wilson's disease, alpha-1-antitrypsin deficiency **Chronic hepatitis**: lymphocytic inflammation (+/- plasma cells) found in portal tract Activity determined by: - Inflammation movement from portal tract into lobule - Degree of hepatocellular damage (apoptotic hepatocytes, cellular swelling- more severe) **Interface hepatitis**: lymphocytes rosette around hepatocytes at the limiting plate (sleeve of hepatocytes around portal tract)- this example shows moderate hepatitis due to prominence of interface inflammation

Answer 63

**Chronic hepatitis lobular inflammation**: with or without hepatocellular damage (apoptotic hepatocytes with cellular swelling) only seen in _severely active cases_. Can see lymphocytes in Zone 1, 2, 3 and apoptotic hepatocytes (councilman body) **Below:** Chronic hepatitis severely active: HBV with HDV superinfection - See interface AND lobular inflammation \* Remember: **grading** is based on activity/location of **lymphocytes**/ amount of **inflammation** (portal tract---\> lobular) while **staging** is based on amount of **fibrosis**

Answer 64

**Hepatitis B "ground glass"** Enveloped, dsDNA virus - **Progresses to chronic disease** in 90% of infants infected (enveloped), **only 5% in adults** - Acute illness in 35% (0.5% fulminant hepatitis--\> necrosis, mortality) \* Increases risk for hepatocellular carcinoma (even outside of cirrhosis) - **Labs: serum HBsAg** - Histo: "ground glass" appearance

Answer 65

HBV with HDV superinfection Envelope (from HBV infection), ssRNA virus - Can ONLY Infect HBV-infected cells - Co-infection: aggressive (2-20% mortality) * *- Superinfection: Chronic HBV with worsened condition (due to HDV)= 30% mortality** - Higher risk of acute liver failure, cirrhosis, no clear association with HCC - Associated with drugs, dependent on B

Answer 66

Hepatitis C infection: tightly formed lymphoid aggregate in portal tract Enveloped, ssRNA virus * *Labs: anti-HCV+, RT-PCR for viral HCV RNA** - Seldom seen in acute phase - 85% chronically infected (enveloped)--\> 20% develop cirrhosis - 10% cirrhotic individuals develop hepatocellular carcinoma

Answer 67

Autoimmune hepatitis closely ressembles chronic viral hepatitis- MUST correlate with clinical and serologic findings. - **numerous plasma cells**= histological clue - more active than hepatitis **_Features_**: - More common in women (70%) - Histology "perals: chronic pattern of injury, **plasma cells, moderate to severe activity on biopsy** - Exclude viral causes/drug reactions - **ANA+** (60%), **ASMA** + (70%)= type 1 - Anti-LKA (type 2- pediatric) - Anti-SLA (type 3- rare) - **Hypergammaglobulinemia** - **Brisk response to steroids** (bridging necrosis= bad--\> completely resolved by steroids) **ANA**= anti-nuclear antibody, **ASMA= anti-smooth muscle antibody**, LKM= anti-liver kidney microsomal, SLA= anti-soluble liver antigen

Answer 68

**Bile duct obstruction--\> Biliary injury to portal tract** Mixed infiltrate in portal tract: - neutrophils= acute peri-cholangitis: acute inflammation around bile ducts; reaction to bile salts (destruction of tissue) \* Not seen **IN** bile duct (within duct indicates ascending infection= acute cholangitis) - lymphocytes: metaplasia of bile ducts in response to bile salt exposure (to protect hepatocytes) can cuase leakage into portal connective tissue--\> lymphocytic infiltration - eosinophils **below**: bile ductular proliferation (small ducts at limiting plate= metaplastic process, reaction to bile salts). May be bypass mechanism to help drain bile--\> ductular cells can absorb bile salts to protect hepatocytes (reabsorption will then cause leakage into portal connective tissue--\> marked lymphocyte response)

Answer 69

* *Cholate stasis**= damage from bile salts causes cellular swelling of hepatocytes ("feathery degeneration") - Seen in **zone 1** Woman has **Primary biliary cholangitis** * *Below**: **Cholestasis**: increasing inability to excrete bile--\> bile pigment from bilirubin accumulates within lobule - seen in **zone 3**

Answer 70

**Bile infarct=** sign of extrahepatic biliary obstruction (for example, **primary sclerosing cholangitis**) **Below**: biliary sludge due to PSC

Answer 71

**Primary biliary cirrhosis/cholangitis**: causes **bile duct lesions** due to lymphocytic infiltration (from excess bile salt)--\> leads to ductopenia (bile duct loss). - Differentiate from chronic hepatitis: prominent duct damage, mixed infiltrate (neutrophils and eosinophils) and **granuloma** **Granuloma** (below)= not speciifc for PBC (can also be seen in hepatic sarcoidosis, drug reaction, infectious etiologies _Clinical features of PBC_: Female Early signs: - Asymptomatic with elevated alkaline phosphatase (out of proportion to bilirubin) - Pruritis without Jaundice - Malabsorption of fat-soluble vitamin ( can lead to elevated INR in absence of end-stage liver disease due to decreased Vit K absorption) Later signs: - Xanthomas - Osteoporosis (Vit D malabsorption) - Jaundice, ascites, portal HTN (liver failure) Histo: - Involves intrahepatic bile ducts (MICROscopic) - See bile duct lesions (lymphocytic infiltration/granulomatous inflammation) - Chronic non-suppurative destruction cholangitis - Leads to ductopenia/fibrosis _Treatment of PBC_: - Urosodeoxycholic acid (UDCA) - Cholestyramine= relieves pruritis - Liver transplantation in advanced cases

Answer 72

Lymphoplasmacytic cholecystitis: lymphoplasmacytic infiltrate in gallbladder. Occurs in distal bile duct obstruction _in the absence of gallstones_**- seen in PSC**

Answer 73

**Alcoholic Steatohepatitis**: can see steatosis and lobular inflammation and injury (**cellular swelling/ballooning- below**), lymphocytic inflammation of lobules, presence of **Mallory bodies (**bottom). Indicative of steatohepatitis due to macrovesicular steatosis and cellular swelling/ swollen mitochondria Mallory bodies= ubiquinated cytokeratins 8, 18. It is likely this man has been drinking at least 100-150 g of alcohol a day \* AST/GGT synthesis enhanced by alcohol metabolism---\> AST/ALT ratio \>1 (2), GGT elevations

Answer 74

**"Chicken-wire" fibrosis** seen in steatohepatitis (predominantly in zone 3) **Below**: ASH- alcoholic steatohepatitis--\> **Glycogenated Nuclei and megamitochondria**. More commonly seen in ASH than NASH.

Answer 75

**Endoscopic retrograde cholangiopancreatography (ERCP**)= diagnostic gold standard for **primary sclerosing cholangitis**, potential to apply therapy (opening strictures) Treatment: - NONE - treat for cholangitis - open strictures, monitor for cancer - Liver transplant curative, can recur

Answer 76

**Metastatic liver malignancy:** Most common malignancy of liver Seen in **non-cirrhotic** liver- metastases don't like cirrhotic liver. Come from colon, pancreas, **breast**, lung

Answer 77

**Alpha fetoprotein** (seen in 50% of people with **HCC-** in this case due to chronic Hep C infection) **Histo:** Expansion of liver plates visible

Answer 78

* *Focal nodular hyperplasia**: - Benign non-neoplastic mass; arises in non-cirrhotic liver - Asymptomatic- rarely grows or bleeds, no malignant potential - Occasionally resected to differentiate from hepatic adenoma, tumors - **More common in Women, age 20-50** * *Histo**: - Comes from malformation of arteries in center of nodules-- central "stellate scar" (below) - Fibrous bridges with dysplastic (malformed) arteries, without accompanying bile duct/vein. At edges of fibrosis, see ducts/veins - Non-neoplastic: arises from alternating hepatocyte hyperplasia and atrophy due to malformed arteries

Answer 79

* *Nodular regenerative hyperplasia**= non-cirrhotic portal hypertension; occurs in: - **Autoimmune disease**, hypercoagulability disorders, hematologic disorders, portal vein thrombosis, drugs - Zone 3 deprived of nutritionally rich blood from portal tract--\> sinusoidal dilation, nodular appearance **Histo**: See **zone 3 nutritional atrophy**--\> sinusoidal dilation and _NO fibrosis_ - May also see **portal tract venopathy** (venous obliteration/narrowing) \* NOT regenerative or hyperplastic!

Answer 80

**Zone 3 necrosis** caused by **acetaminophen toxicity**. Also seen in carbon tetrachloride exposure, severe hypoperfusion from shock or left sided heart failure. Infarcts are uncommon as liver has 2 blood supplies- portal venous and hepatic arterial system (therefore entire system needs to lose blood, not just infarct of hepatic artery) - **Seen in Zone 3= furthest from blood supply** (last dibs- most vulnerable to ischemia) * *Treatment**: 1. Rehydration (vomiting/diarrhea) 2. Acetaminophen overdose needs STAT administration of **N-acetylcysteine** (mimics function of glutathione which is depleted by alcohol ingestion--\> breaks down toxic ethanol metabolites)- best if administered **within 16 hours of ingestion** 3. Liver transplant- most of the damage has already occured- will need a new liver **\*** 40% of acute liver failure (ALF) due to acetaminophen toxicity (occurs in anyone receiving sufficient dose) 60% ALF due to idiosyncratic drug reactions

Answer 81

**Acute hepatitis**. Acute viral hepatitis are NOT cytopathic--\> injury due to T-cells eliminating infection by killing infected hepatocytes. * *Diagnostics**: 1. Serology (NOT biopsy- despite example) to discover cause of hepatitis: - Hep A: Anti-HAV IgM (patient likely had immunization before leaving for Asia- test positive for **Anti-HAV IgG**) - Hep B: Anti-HBc IgM (likely immunized, would test positive for **Anti-HBs)** - Hep C: HCV RNA (unlikely to have acute infection- chronicity more common. history of IVD use?) - Hep D: Would need concomittant HBV infection - **Hep E: anti-HEV IgM**- no vaccine, _no long-term risks unless pregnant_)- Most likely diagnosis based on history of travel and adequate vaccination history. 2. Biopsy ONLY if acute hepatitis source indeterminate or trying to assess amount of injury/fibrosis **Below**: hepatocellular dropout in acute advanced hepatitis--\> parenchymal collapse--\> mimics fibrosis ("bridging necrosis"). Can also see cholestasis (hepatocytes fail to move bile out of liver) **Histo:** **lymphocytic infiltrate**, lobular hepatitis- see cellular swelling, architectual disarray. Cellular swelling and apoptotic hepatocytes (councilman bodies) visible. \* Can also see "flare" of chronic hepatitis- resembles lobular changes, BUT there would also be portal inflammation

Answer 82

Histologic specimen of normal small intestine **Below**: plica circulares

Answer 83

**Normal small bowel mucosa** A villous height-‐to-‐crypt depth ratio of 3:1 to 5:1. Less than 20 intraepithelial lymphocytes per 100 enterocytes, distributed in a decrescendo pattern (i.e. less concentrated at the tips) The lamina propria contains a mild physiologic mix of plasma cells, lymphocytes, and occasional eosinophils.

Answer 84

**Brunner's glands** within duodenum

Answer 85

**Terminal ileum**: see peyer's patches (lympoid aggregates), villi with crypts of Lieberkuhn. Absorptive cells blend and are lined by thin ribbon (brush border) with interspersed goblet cells

Answer 86

Normal Colonic Histo: "test tubes in a rack" **Below**: Haustral folds

Answer 87

**Lymphocytic colitis**= form of microscopic colitis - F: M ratio 3:1 - Increased intraepithelial lymphocytes - No increased subepithelial collagen - Lamina propria: increased lymphocytes, plasma cells, eosinophils Microscopic colitis= chronic watery (non-bloody) diarrhea, normal endoscopy), typically seen in middle-aged and elderly patients, idiopathic, sometimes associated with long-term NSAIDs, celiac disease Therapy: dietary, drug modification. Budesonide (glucocorticoid with mucosal activity and little systemic activity) **Below**: unremarkable changes in colon surface on gross examination

Answer 88

**Collagenous colitis**= form of microscopic colitis - F:M ratio 8:1 - Increased intraepithelial lymphcytes - **Thickened subepithelial collagen** (pink) - Increased lymphocytes, plasma cells, eosinophilas in lamina propria - No architectural changes (no crypt distortion unlike UC/Crohn disease) Microscopic colitis= chronic watery (non-bloody) diarrhea, normal endoscopy), typically seen in middle-aged and elderly patients, idiopathic, sometimes associated with long-term NSAIDs, celiac disease **Therapy**: dietary, drug modification. Budesonide (glucocorticoid with mucosal activity and little systemic activity) **Below:** no changes in colonic surface on colonoscopic exam