Gastrointestinal Pathology Flashcards
Painful, superficial ulceration of oral mucosa characterized by grayish base surrounded by erythema; arises in relation to stress and resolves spontaneously, but often recurs
Apthous ulcer
Recurrent aphthous ulcers, genital ulcers, and uveitis due to immune complex vasculitis involving small vessels; can be seen after viral infection but etiology is unknown
Behcet syndrome
HSV-1 primary infection occurs in childhood. The lesions heal, but the virus remains dormant in ganglia of ______ nerve. Stress and sunlight cause reactivation of the virus, leading o vesicles that often arise on the lip
Trigeminal
SCC is a malignant neoplasm of squamous cells lining the oral mucosa. _____ and ______ are major risk factors, and the floor of the mouth is the most common location
Tobacco; alcohol
What are the 2 potential precursor lesions to SCC that are often biopsied to r/o carcinoma?
Leukoplakia
Erythroplakia (vascularized leukoplakia)
[note hairy leukoplakia at the lateral sides of the tongue in an immunocompromised state is a manifestation of EBV and represents hyperplasia of squamous mucosa — this is not dysplasia or a precursor to SCC]
Infection with mumps virus results in bilateral inflamed parotid glands. What are 3 other potential clinical manifestations with mumps infection?
Orchitis (carries risk of sterility in teens)
Pancreatitis
Aseptic meningitis
With mumps virus infection, serum _____ is increased due to salivary gland or pancreatic involvement
Amylase
Inflammation of the salivary gland is called _______. This is most commonly due to obstructing stone (sialolithiasis) leading to infection caused by ________. It is usually unilateral
Sialadenitis; S.aureus
Most common tumor of salivary gland; Benign tumor usually arising in parotid that is composed of stromal (e.g., cartilage) and epithelial tissue (e.g., glands). Described as mobile, painless, circumscribed mass at the angle of the jaw
Pleomorphic adenoma
Why is there a high rate of recurrence with pleomorphic adenoma of the salivary gland?
Extension of small islands of tumor through tumor capsule often results in incomplete resection
Rarely, a pleomorphic adenoma of the salivary gland may transform into carcinoma. This presents with signs of ________ damage
Facial n.
2nd most common tumor of salivary gland; benign cystic tumor with abundant lymphocytes and germinal centers that almost always arises in the parotid
Warthin tumor
Malignant tumor composed of mucinous and squamous cells, usually arises in parotid and commonly involves the facial nerve
Mucoepidermoid carcinoma
Tracheoesophageal fistula is a congenital defect resulting in connection between the esophagus and trachea. In the most common variant, there is atresia of the esophagus (resulting in a blind pouch), and the distal esophagus arises from the trachea. What are the 4 major clinical features associated with this defect?
Vomiting
Polyhydramnios
Abdominal distention (air going into stomach)
Aspiration (food going up into the lungs)
An esophageal web is a thin protrusion of esophageal mucosa, most often in the upper esophagus, that presents with dysphagia for poorly chewed food. These pts are at an increased risk for what malignancy?
Esophageal squamous cell carcinoma
[note this is protrusion of mucosa only!]
3 features of plummer vinson syndrome
Severe iron deficiency anemia
Esophageal web
Beefy red tongue due to atrophic glossitis
Outpouching of pharyngeal mucosa through ACQUIRED defect in the muscular wall arising above upper esophageal sphincter at junction of esophagus and pharynx. Presents with dysphagia, obstruction, and halitosis
Zenker diverticulum
[FALSE diverticulum]
Longitudinal laceration of mucosa at gastroesophageal junction caused by severe vomiting, usually due to alcoholism or bulimia; presents with PAINFUL hematemesis
Mallory-Weiss Syndrome
[at increased risk for Boerhaave syndrome — presents with subcutaneous emphysemia due to air in mediastinum]
Esophageal varices are dilated submucosal veins in lower esophagus that arise secondary to portal HTN. They are usually asymptomatic, but at risk of rupture (PAINLESS hematemesis). Backup of blood in what vein leads to this dilation?
Left gastric v.
Most common cause of death in cirrhosis
Esophageal variceal bleeding
Achalasia is disordered esophageal motility with inability to relax LES. It is caused by damaged ganglion cells in the _____ _______. Damage can be idiopathic or secondary to known insult (e.g., Chagas disease)
Myenteric plexus
[runs between inner circular and outer longitudinal layer of muscularis propria]
Clinical features of achalasia include dysphagia for solids AND liquids, putrid breath, high LES pressure on esophageal manometry, and bird-beak sign on barium swallow. These pts are at increased risk for what malignancy?
Esophageal SCC
Bowel sounds in the lower lung field indicates what?
Paraesophageal hernia
[these pts may also have lung hypoplasia if the hernia is congenital]
Risk factors for GERD include what type of hernia?
Sliding hiatal hernia
[other risk factors are alcohol, tobacco, obesity, fat-rich diet, caffeine, and hiatal hernia]
Barrett’s esophagus may result in the setting of GERD, and is characterized by a change in the normal __________ epithelium of the lower esophagus into a __________ epithelium with _____ cells
Non-keratinized squamous; non-ciliated columnar; goblet
Esophageal carcinoma is subclassified into adenocarcinoma or squamous cell carcinoma. Which one is the most common esophageal cancer worldwide and arises in upper or middle third of esphagus?
SCC
[adenocarcinoma is the most common in the West and arises in the lower 1/3]
Risk factors for esophageal SCC include alcohol, tobacco, very hot tea, achalasia, esophageal webs (e.g., plummer vinson syndrome), esophageal injury (e.g., lye ingestion). This type of cancer often presents late in the course with what types of signs/symptoms?
Progressive dysphagia, weight loss, pain, and hematemesis (similar to adenocarcinoma)
Additional findings of hoarse voice (recurrent laryngeal n. involvement), and cough (tracheal irritation)
Region of LN spread for esophageal carcinoma of the upper 1/3, middle 1/3, and lower 1/3
Upper 1/3 = Cervical nodes
Middle 1/3 = Mediastinal or tracheobronchial nodes
Lower 1/3 = Celiac and gastric nodes
Congenital malformation of abdominal wall leading to exposure of abdominal contents
Gastroschisis
Persistent herniation of bowel into umbilical cord due to failure of herniated intestines to return to body cavity during development
Omphalocele
Omphalocele contents are covered by ______ and _______ of umbilical cord
Peritoneum; amnion
Pyloric stenosis is congenital hypertrophy of pylorus presenting with projectile nonbilious vomiting, visible peristalsis, and an olive like mass in the abdomen. When does this condition classically present?
2 weeks after birth
[tx is myotomy]
Gastritis can be subclassified as acute or chronic. Acute gastritis is caused by acidic damage to the mucosa due to an imbalance between mucosal defenses and the acidic environment. Acidic damage results in superficial inflammation, erosion (loss of epithelium) and ulcer (loss of mucosal layer)
Risk factors for acute gastritis include severe burn (hypovolemia leading to _______ ulcer), NSAIDs (due to loss of ______ protection), heavy alcohol consumption, chemotherapy, increased intracranial pressure (_______ ulcer), and shock
Curling; prostaglandin; Cushing
How does increased intracranial pressure lead to acute gastritis?
Increased intracranial pressure results in increased vagal stimulation resulting in increased acetylcholine release, which binds parietal cell to increase acid production
Chronic gastritis can be divided into 2 types based on underlying etiology: autoimmune gastritis and H.pylori gastritis (most common). Chronic autoimmune gastritis involves autoimmune destruction of gastric parietal cells, which are predominantly present in the ___ and ____ of the stomach. This is associated with antibodies against _____ and/or ______ which are useful for dx
Body; fundus; parietal cells; intrinsic factor
What type of HSR is chronic autoimmune gastritis?
Type IV HSR — CD8+ mediated damage
Clinical features of chronic autoimmune gastritis include atrophy of mucosa, achlorhydria with increased ______ levels and antral _____ hyperplasia, and megaloblastic (pernicious) anemia due to lack of __________
Gastrin; G-cell; intrinsic factor
Chronic autoimmune gastritis induces intestinal _______, which leads to increased risk for gastric _______
Metaplasia; adenocarcinoma
[metaplasia is indicated by increased goblet cells]
H.pylori-induced acute and chronic inflammation results in chronic H.pylori gastritis. The ___ and ____ released by H.pylori along wtih inflammation lead to weakening of mucosal defenses. The _____ of the stomach is the most common site affected
Ureases; proteases; antrum
H.pylori infection presents wtih epigastric abdominal pain. These pts are at increased risk for ulceration and what 2 types of malignancy?
Gastric adenocarcinoma
MALT lymphoma
Treatment of H.pylori involves triple therapy, which resolves gastritis/ulcer and reverses intestinal metaplasia. What 2 tests confirm eradication of H.pylori?
Negative urea breath test
Lack of stool antigen
Peptic ulcer disease involves a solitary mucosal ulcer involving the _____ _____ (90% of cases) or the ____ ____ (10% of cases)
Proximal duodenum; distal stomach
A ______ ulcer is almost always due to H.pylori; rarely due to ZE syndrome. This type of ulcer presents with epigastric pain that ______ with meals. Diagnostic endoscopic biopsy showing ulcer with hypertrophy of ____glands
Duodenal; improves; Brunner
One of the complications of duodenal ulcer is rupture, which leads to bleeding from the _______ artery, or acute pancreatitis (both of these are complications of ________ ulcers)
Gastroduodenal a.; posterior
Gastric ulcers are usually due to H.pylori, but other causes include NSAIDs and bile reflux. They present with epigastric pain that _____ with meals. The ulcer is usually located on the ____ curvature of the antrum. Rupture carries the risk of bleeding from the ________ artery
Worsens; lesser; left gastric a.
Ddx of ulcers includes cancer. While _____ ulcers are almost never malignant, _____ ulcers can be caused by associated carcinoma
Duodenal; gastric
Gastric carcinoma is a malignant prolferation of surface columna epithelial cells (adenocarcinoma). Gastric carcinoma can be subclassified into what 2 types?
Intestinal type
Diffuse type
The ______ type of gastric adenocarcinoma presents as large, irregular ulcer with heaped up margins, most commonly involving lesser curvature of antrum. Risk factors include intestinal metaplasia, nitrosamines in smoked foods, and blood type A.
Intestinal
The _____ type of gastric adenocarcinoma involves signet ring cells that infiltrate the gastric wall. Desmoplasia results in thickening of the stomach wall in a condition called ____ _____. This is NOT associated with H.pylori, intestinal metaplasia, or nitrosamines
Diffuse; linitis plastica
[signet ring cell = cell with nucleus pushed to side by mucous]
Gastric carcinoma presents late, with weight loss, abdominal pain, anemia, and early satiety. Rarely, it may present with skin findings of ______ ______ or ______ _____ sign
Acanthosis nigricans; Leser-Trelat
Gastric adenocarcinoma often spreads to what unique lymph node?
LEFT supraclavicular node (Virchow node)
Distant metastasis of gastric adenocarcinoma most commonly involves what organ?
Liver
Distant metastasis of gastric adenocarcinoma most commonly involves the liver. Involvement of the periumbilical region is called the Sister Mary Joseph nodule, which is classically seen with the ____ type of gastric cancer.
Involvement of the bilateral ovaries (krukenberg tumor) is classically seen with the _____ type of gastric cancer
Intestinal
Diffuse
Infant presents with polyhydramnios, distension of stomach and blind loop of duodenum (‘double-bubble’ sign on xray), and bilious vomiting
Duodenal atresia
[congenital failure of the duodenum to canalize. Pts with Down syndrome are at increased risk]
Meckel diverticulum is outpouching of all 3 layers of bowel wall (true diverticulum); arises due to failure of _________ to involute
Vitelline duct
[normally involutes by 7th week gestation; most severe form causes fecal matter to drain from umbilicus]
Rule of 2s of meckels diverticulum
Seen in 2% of the population (most common congenital anomaly of GI tract)
2 inches long
Located in small bowel within 2 feet of ileocecal valve
Presents in first 2 years of life with bleeding, volvulus, intussusception (although most cases are asymptomatic)
Why do meckel’s diverticula sometimes bleed?
May contain heterotopic gastric tissue which secretes acid, damaging bowel wall and leading to bleeds
A volvulus is a twisting of bowel along its mesentery, resulting in obstruction and disruption of blood supply (infarction). What is the most common location in elderly vs. young adults?
Elderly = sigmoid colon
Young adults = cecum
Intussusception is telescoping of the proximal segment of bowel into the distal segment resulting in infarction or obstruction, which may present with current jelly stools. The primary risk factor is a leading edge, and in children the most common cause is ________ _______, while in adults, the most common cause is _______
Lymphoid hyperplasia (terminal ileum dragged into cecum); tumor
Small bowel is highly susceptible to ischemic injury. A transmural infarction occurs with embolism/thrombosis of the ______ artery or thrombosis of the ______ vein.
A ______ infarction (as opposed to transmural) occurs with marked hypotension
Superior mesenteric a.; mesenteric
Mucosal
[causes of transmural infarction include atrial fibrillation, vasculitis, lupus anticoagulant, etc.]
Clinical features of intestinal infarct are abdominal pain, bloody diarrhea, and ______ bowel sounds
Decreased
Lactose intolerance is due to decreased function of the lactase enzyme found in brush border of enterocytes. Clinical presentation is abdominal distension and diarrhea on consumption of milk products. Deficiency may be congenital or acquired. What are 2 ways in which deficiency is acquired?
Acquired with age
Following infection that damages enterocytes (lactase function returns upon healing)
Celiac disease is immune-mediated damage of small bowel villi due to gluten exposure. What are the 2 HLA associations?
HLA-DQ2 and DQ8
More on pathogenesis of celiac disease: Gluten is present in wheat and grains. The most pathogenic component is gliadin. Gliadin is ________ by tissue transglutaminase, the product of this reaction is then presented by APCs via _______ and _______ T cells mediate tissue damage. Presents clinically in children with abdominal distension, diarrhea, and failure to thrive, and in adults with chronic diarrhea and bloating
Deamidated; MHC II; helper (CD4)
What is the pathogenesis of dermatitis herpetiformis, the skin manifestation of celiac disease?
IgA deposition at tips of dermal papillae
Lab findings of celiac disease include IgA antibodies against ______, ______, or _______.
In the case of IgA deficiency, _____ antibodies are useful for diagnosis
Endomysium, tTG, or gliadin
IgG
Duodenal biopsy in a celiac disease patient would show flattening of villi, ______ of crypts, and increased intraepithelial lymphocytes.
Damage is most prominent in the _______, while the _____ and _____are less involved
Hyperplasia
Duodenum; jejunum; ileum
Symptoms of celiac disease resolve with a gluten-free diet. If a patient presents with refractory disease despite good dietary control, what should you check them for?
Small bowel carcinoma
T-cell lymphoma (enteropathy-associated T cell lymphoma aka EATL)
[note that T cell lymphoma is a rare occurence but this is one case where you may see it]
______ ______ = damage to small bowel villi due to unknown organism, resulting in malabsorption. Occurs in tropical regions (e.g., Caribbean), arises after infectious diarrhea, and responds to antibiotics
Tropical sprue
What is the primary difference between celiac disease and tropical sprue regarding site of most prominent damage?
Celiac = damage most prominent in duodenum
Tropical sprue = damage most prominent in jejunum and ileum
Whipple disease = systemic tissue damage characterized by ______ loaded with Tropheryma whippelii organisms. Partially destroyed organisms are present in the _______ of these cells, which stain positive for ____
Macrophages; lysosomes; PAS
Classic site of involvement for tropheryma whippelii (results in fat malabsorption and steatorrhea)
Small bowel lamina propria
[other common sites of involvement include synovium of joints (leading to arthritis), cardiac valves, lymph nodes, and CNS]
Abetalipoproteinemia is a ________ _______ inherited deficiency of apolipoprotein ____ and _____
Autosomal recessive; B-48; B-100
Abetalipoproteinemia is a autosomal recessive inherited deficiency of apolipoprotein B-48 and B-100.
This results in malabsorption due to defective ______ formation, which requires B-48, and absent plasma _____ and _____, which requires B-100
Chylomicron; VLDL; LDL
Carcinoid tumor is a low-grade malignant proliferation of neuroendocrine cells that is positive for __________. These can arise anywhere along the gut, but the _______ is the most common site. They grow as a submucosal polyp-like nodule.
These tumors often secrete serotonin, and its metabolite ______ is excreted in the urine. Detection of this molecule is the only way to detect carcinoid tumor prior to metastasis to the liver.
Chromogranin; small bowel
5-HIAA
Carcinoid syndrome is bronchospasm, diarrhea, and flushing of the skin. Symptoms can be triggered by EtOH or emotional stress. Another advanced manifestation is carcinoid heart disease, what are the features?
Right-sided valvular fibrosis leading to tricuspid regurgitation and pulmonary valve stenosis
[due to deposition of collagen in the valves. There is no left-sided valvular disease because monoamine oxidase in the lung is able to metabolize serotonin being pumped in by the right side of the heart]
Acute appendicitis is acute inflammation of the appendix, and is the most common cause of acute abdomen. It is related to obstruction of the appendix by ______ _____ (children) or ______ (adults)
Lymphoid hyperplasia; fecalith
Classic presentation is young women (teens to 30s) with recurrent bouts of blood diarrhea and abdominal pain; more prevalent in the West, particularly caucasians and eastern european jews
Irritable bowel disease
[considered a dx of exclusion because symptoms mimic other causes of bowel inflammation]
UC or Crohns:
Mucosal and submucosal ulcers beginning in rectum and can extend proximally up to the cecum; involvement is continuous and remainder of GI tract is unaffected
UC
UC or Crohns:
Full-thickness inflammation with knife-like fisures; occurs anywhere from mouth to anus with skip lesions. Terminal ileum is most common site, rectum is less commonly involved
Crohns
In terms of irritable bowel disease, smoking is protective against _____, but increases the risk for ______
UC; Crohns
UC or Crohns?
Right lower quadrant pain and diarrhea
Crohns
[diarrhea is typically non-bloody; UC typically presents with LLC pain and bloody diarrhea]
UC or Crohns?
Lymphoid aggregates with granulomas
Crohns
UC or Crohns?
Pseudopolyps and loss of haustra
UC
[loss of haustra —> lead pipe sign on imaging]
UC or Crohns?
Crypt abscesses with neutrophils
UC
UC or Crohns?
Cobblestone mucosa, creeping fat, and strictures
Crohns
[string-sign on imaging]
UC or Crohns?
Toxic megacolon and carcinoma; primary sclerosing cholangitis and p-ANCA positivity
UC
[risk is based on extent of colonic involvement and duration of disease; generally not a concern until >10 years of disease]
UC or Crohns?
Malabsorption with nutritional deficiency, calcium oxalate nephrolithiasis, fistula formation and carcinoma if colonic disease is present
Crohns
UC is associated with primary sclerosing cholangitis and p-ANCA positivity. What are the 5 major systemic associations of Crohns disease?
Ankylosing spondylitis
Sacroiliitis
Migratory polyarthritis
Erythema nodosum
Uveitis
Hirschprung disease = defective relaxation and peristalsis of the rectum and distal sigmoid colon; associated with Down syndrome. This is caused by a congenital failure of ganglion cells to descend. Clinical features are based on obstruction, including failure to pass meconium, empty rectal vault on DRE, massive dilation of bowel proximal to obstruction (risk of rupture), and a rectal suction biopsy will reveal lack of ganglion cells. A rectal suction biopsy checks for ganglion cells in what layer of the bowel wall?
Submucosa (meissners plexus) — although ganglion cells are also missing from auerbachs myenteric plexus between inner circular and outer longitudinal layer of muscularis propria as well
Colonic diverticula are outpouchings of _____ and _____ through the _______
Mucosa; submucosa; muscularis propria
[this is a pseudodiverticulum because it is only 2 layers]
Colonic diverticula are related to wall stress — so they are associated with constipation and low-fiber diet and are commonly seen in older adults. The diverticula arise where the __________ traverse the muscularis propria, as this creates a weak point in the colonic wall. The _______ colon is the most common location
Vasa recta; sigmoid
Acquired malformation of mucosal and submucosal capillary beds, usuall arising in the cecum and right colon due to high wall tension. Presents as hematochezia in an older adult
Angiodysplasia
Autosomal dominant disorder resulting in thin-walled blood vessels, especially in nasopharynx and GI tract; rupture presents as bleeding
Hereditary Hemorrhagic Telangiectasia
Ischemic colitis = ischemic damage to the colon, usually at the splenic flexure. Presents with postprandial pain and weight loss. Infarction results in pain and bloody diarrhea. What is the most common cause of ischemic colitis?
Atherosclerosis of the SMA
Relapsing abdominal pain with bloating, flatulence, and change in bowel habits (diarrhea or constipation) that improves with defecation; classically seen in middle-aged females
Irritable bowel syndrome
Most common type of colon polyp; caused by hyperplasia of the glands and exhibits ‘serrated’ appearance on microscopy. Usually arise in left colon (rectosigmoid). Considered benign with no malignant potential
Hyperplastic polyp
Type of colon polyp that is a neoplastic proliferation of glands. Considered benign, but premalignant and may progress to adenocarcinoma via the adenoma-carcinoma sequence
Adenomatous polyp
Adenomatous polyps may progress to adenocarcinoma via the adenoma-carcinoma sequence. What is this sequence?
APC gene mutation (tumor suppressor on Chr 5) creates potential to develop polyps
KRAS mutation causes actual polyp development
P53 mutation and increased COX expression (aspirin protects against this sequence) — polyp becomes malignant
Risk for polyp progession from adenoma to carcinoma is related to what 3 worrisome colonoscopy findings?
Size > 2 cm
Sessile growth
Villous histology
Gardner syndrome is familial adenomatous polyposis + _________ + __________
Fibromatosis
Osteomas
______ syndrome = familial adenomatous polyposis + CNS tumors (medulloblastoma and glial tumors)
Turcot syndrome
A juvenile polyp is typically a sporadic _______ polyp (benign) that arises in children <5 years; usually presents as a solitary rectal polyp that prolapses and bleeds
Hamartomatous
Autosomal dominant disorder characterized by hamartomatous polyps throughout GI tract, mucocutaneous hyperpigmentation on lips, oral mucosa, and genital skin. Associated with increased risk for colorectal, breast, and GYN cancer
Peutz-Jeghers Syndrome
Colorectal cancer peak incidence is 60-70 years of age. It most commonly arises from the adenoma-carcinoma sequence (80% of cases). The second most important molecular pathway is what?
Microsatellite instability (MSI)
HNPCC is the prototypic example of microsatellite instability pathway for development of colorectal carcinoma. It is caused by an inherited mutation in DNA mismatch repair enzymes, and leads to an increased risk of colorectal, _____, and ______ carcinoma. The colorectal carcinoma arises de novo at a relatively early age, and is usually _____-sided
Ovarian; endometrial; right
A ______-sided colon carcinoma tends to grow as ‘napkin-ring’ lesion and presents with decreased stool caliber, pain, and blood-streaked stool
Left
A _____-sided colon carcinoma tends to grow as a raised lesion and presents with iron-deficiency anemia and vague pain
Right
Colorectal carcinoma increases the risk for _____ _____ infectious endocarditis
Streptococcus bovis
TNM staging of colorectal carcinoma
T = depth of invasion
N = spread to regional LNs
M = distant spread; most commonly involves the liver
Serum tumor marker useful for assessing treatment response and detecting recurrence of colorectal carcinoma
CEA
Acute pancreatitis is an inflammation and hemorrhage of the pancreas caused by autodigestion of pancreatic parenchyma by pancreatic enzymes. Premature activation of _____ leads to activation of other enzymes.
The end result is 2 types of necrosis: ______ necrosis of the pancreatic parenchyma, and _________ necrosis of the surrounding tissue due to saponification
Trypsin
Liquifactive; fat
2 major causes of acute pancreatitis
Alcoholism
Gallstones
[other causes = trauma (think seatbelt in children), hypercalcemia, hyperlipidemia, drugs, scorpion stings, mumps, rupture of posterior duodenal ulcer]
Clinical features of acute pancreatitis include epigastric abdominal pain that radiates to the back, N/V, periumbilical and flank hemorrhage, as well as what changes in serum lipase, amylase, and calcium levels?
Elevation of serum lipase and amylase (note that lipase is more specific because amylase can be seen with damage to salivary gland)
Hypocalcemia (due to calcium being lost to deposition in the process of fat necrosis due to saponification)
Complications of acute pancreatitis
Shock
Pancreatic pseudocyst and abscess (fibrous tissue, not a true cyst; would present with persistently elevated amylase)
DIC and ARDS
Chronic pancreatitis is characterized by _____ of pancreatic parenchyma secondary to recurrent acute pancreatitis. It is most commonly due to alcohol in adults and _____ ______ in children; although many cases are idiopathic
Fibrosis; cystic fibrosis
Clinical features of chronic pancreatitis include epigastric pain radiating to the back, pancreatic insufficiency, dystrophic calcification of the pancreas (seen on imaging), secondary _____ ______ (late) and an increased risk for _______ _______
Diabetes mellitus; pancreatic carcinoma
Pancreatic carcinoma is an __________ arising from pancreatic ducts. It is most commonly seen in the elderly. Major risk factors are _____ and _____ _____
Adenocarcinoma; smoking; chronic pancreatitis
Clinical features of pancreatic adenocarcinoma include epigastric pain and weight loss.
What clinical features indicate cancer of the head of the pancreas vs. the body/tail?
Head of pacreas — obstructive jaundice with pale stools and palpable gallbladder
Body or tail — secondary diabetes mellitus (islets are particularly prevalent in body and tail; think of this if a thin elderly person develops new-onset diabetes)
Additional clinical features of pancreatic adenocarcinoma are pancreatitis, and _______ _______ which presents as swelling, erythema, and tenderness in the extremities (seen in 10% of cases)
The serum tumor marker is ______
Migratory thrombophlebitis
CA 19-9
Biliary atresia = failure to form or early destruction of the ______ (intrahepatic/extrahepatic?) biliary tree. This leads to biliary obstruction within the first ______ of life, presenting with jaundice (conjugated bilirubin) and progresses to cirrhosis
Extrahepatic; 3 months
Cholelithiasis is due to precipitation of cholesterol or bilirubin in the bile due to supersaturation, decreased phospholipids (e.g., lecithin) or bile acids, or stasis.
What is the most common type of stone, especially in the west? How does it appear on imaging?
Cholesterol stones; usually radiolucent (don’t show up on xray)
Risk factors for cholesterol stones
Age Estrogen Clofibrate Native American ethnicity Crohn disease Cirrhosis
How do bilirubin stones appear on xray?
Radiopaque
Extravascular hemolysis and biliary tract infection increase the risk of what type of gallstones?
Bilirubin stones
Biliary tract infection is one of the risk factors for bilirubin gallstones, what are some infectious agents that cause biliary tract infection?
E.coli
Ascaris lumbricoides
Clonorchis sinensis
Gallstones are usually asymptomatic but can lead to certain complications
Biliary colic is a complication characterized by waxing and waning RUQ pain due to gallbladder contracting against a stone lodged in the ____ ___
Cystic duct
Gallstones are usually asymptomatic but can lead to certain complications
_____ _____ is a complication characterized by acute inflammation of the gallbladder wall due to impacted stone in the cystic duct, resulting in dilation with pressure ischemia, bacterial overgrowth, and inflammation
Acute cholecystitis
Gallstones are usually asymptomatic but can lead to certain complications
______ _____ is a complication characterized by rokitansky-aschoff sinus formation due to chemical irritation from longstanding cholilithiasis. This presents with vague RUQ pain especially after eating. A longstanding complication of this condition is ______ _______ characterized by dystrophic calcification of the gallbladder wall
Chronic cholecystitis; porcelain gallbladder
[tx is cholecystectomy, especially if porcelain gallbladder is present — because this is a risk for gallbladder cancer!!]
Gallstones are usually asymptomatic but can lead to certain complications
______ _____ is a complication characterized by bacterial infection of bile ducts, usually due to ascending infection with enteric gram-negative bacteria. Presents as sepsis, jaundice and abdominal pain, and is associated with increased incidence with choledocholithiasis
Ascending cholangitis
Gallstones are usually asymptomatic but can lead to certain complications
______ _____ is a complication in which a stone enters and obstructs the small bowel, due to cholecystitis with fistula formation
Gallstone ileus
Gallbladder carcinoma is an adenocarcinoma arising from the glandular epithelium that lines the gallbladder wall. Gallstones are the major risk factor, especially in the setting of porcelain gallbladder. This classically presents as ________ in elderly women and has a ______ prognosis.
Cholecystitis; poor
Jaundice is yellow discoloration of the skin, and the earliest sign is scleral icterus. It is caused by increased serum bilirubin, usually > 2.5 mg/dL, and arises with disturbances in bilirubin metabolism.
______ is the compound that makes the stool brown. It is partially reabsorbed into the blood and filtered by the kidney, making the urine yellow
Urobilinogen
Would jaundice be due to unconjugated or conjugated bilirubin?:
Extravascular hemolysis or ineffective erythropoiesis
Unconjugated
[High levels of UCB overwhelm the conjugating ability of the liver]
Why does extravascular hemolysis or ineffective erythropoiesis result in clinical features including dark urine and increased risk for pigmented bilirubin gallstones?
Dark urine is due to increased urine UROBILINOGEN (unconjugated bilirubin is not water soluble, and thus is absent from urine)
Increased risk for pigmented bilirubin gallstones due to overwhelmed conjugating ability of the liver —> buildup of conjugated bilirubin in BILE
Physiologic jaundice of the newborn is due to a buildup of _________ bilirubin, and is due the fact that the newborn liver has transiently low __________ enzyme activity
Unconjugated; Uridine glucuronyltransferase
Physiologic jaundice of the newborn is associated with increased unconjugated bilirubin. UCB is fat soluble and can deposit in the _____ ______, leading to kernicterus which results in neurologic deficits and death.
Treatment is phototherapy — what effect does this have?
Basal ganglia
Phototherapy makes UCB water soluble (does NOT conjugate the bilirubin)
Gilbert syndrome is a ______ _____ inherited condition resulting in mildly low UGT activity, resulting in a buildup of ______ bilirubin and subsequent jaundice in times of stress (e.g., severe infection) but is otherwise clinically insignificant
Autosomal recessive; unconjugated
Complete absence of UGT resulting in buildup of unconjugated bilirubin, kernicterus, and is usually fatal
Crigler-Najjar syndrome
Dubin-Johnson syndrome is an autosomal recessive deficiency of _____________, resulting in a buildup of _________ bilirubin.
Clinical features include a dark pigmentation to the liver, but it is otherwise clinically insignificant. _______ syndrome is similar, but lacks liver discoloration
Bilirubin canalicular transport protein; conjugated
Rotor
Biliary tract obstruction (obstructive jaundice) is associated with gallstones, pancreatic carcinoma, cholangiocarcinoma, parasites, and the liver fluke ______ _______.
Lab findings include increased _______ bilirubin, ______ urine urobilinogen, and ________ alkaline phosphatase
Clonorchis sinensis
Conjugated; decreased; increased
Biliary tract obstruction leads to obstructive jaundice with clinical features including dark urine due to bilirubinuria, pale stool, pruritis due to increased plasma _____ _____, hypercholesterolemia with xanthomas, and ________ with malabsorption of fat-soluble vitamins
Bile acids; steatorrhea
What causes jaundice due to an increase in BOTH conjugated and unconjugated bilirubin?
Viral hepatitis — inflammation disrupts hepatocytes and small bile ductules resulting in an increase in both UCB and CB
Additional clinical features include dark urine due to increased urine bilirubin. Urine urobilinogen is normal or decreased
Viral hepatitis is inflammation of the liver parenchyma. It is usually due to hepatitis virus, but other viral causes may include ____ and _____
EBV; CMV
Acute hepatitis presents with jaundice (mixed CB and UCB) with dark urine (CB), fever, malaise, and nausea. Labs show elevated ALT>AST, and symptoms last <6 months.
T/F: the mechanism of destruction of hepatocytes in acute hepatitis is necrosis
False — it is apoptosis due to CD8 T-cell-mediated killing
Chronic hepatitis is defined as hepatitis symptoms >6 months; this condition carries increased risk of progression to cirrhosis.
T/F: in chronic hepatitis, inflammation primarily affects the portal tracts
True
What type of viral hepatitis is associated with fulminant hepatitis in pregnant women (liver failure with massive liver necrosis)?
Hepatitis E
What 2 hepatitis viruses are fecal-oral transmission?
HAV
HEV
[HAV is commonly acquired by travelers; HEV is commonly acquired from contaminated water or undercooked seafood. Between the two, only HAV has an available vaccine]
Labs reveal +HBsAg, +HBeAG, +HBV DNA, +HBcAB IgM, and negative HBsAB. Which of the following describes the patient?
A. Acute stage HBV infection B. Window stage HBV infection C. Resolved HBV infection D. Chronic HBV infection E. Immunization
A. Acute stage HBC infection
[note that HBsAg is first serologic marker to rise]
Labs reveal +HBcAb IgM, and negative HBsAg, HBeAg, and HBsAb. Which of the following describes the patient?
A. Acute stage HBV infection B. Window stage HBV infection C. Resolved HBV infection D. Chronic HBV infection E. Immunization
B. Window stage HBV infection
Labs reveal +HBsAb IgG, and negative HBsAg, HBeAg, and HBcAb. Which of the following describes the patient?
A. Acute stage HBV infection B. Window stage HBV infection C. Resolved HBV infection D. Chronic HBV infection E. Immunization
E. Immunization
T/F: HBV is the most likely of the hepatitis viruses to become chronic
False — HCV is most likely to become chronic
With HCV infection, ________ test confirms infection, and decreased levels of this compound indicate recovery
HCV-RNA
Cirrhosis is characterized by end-stage liver damage due to disruption of normal hepatic parenchyma by bands of fibrosis and regenerative nodules of hepatocytes.
The fibrosis is mediated by ________ secreted by _______ cells. These cells lie beneath the endothelial cells that line the _______ of the hepatic plates
TGF-beta; stellate; sinusoids
Cirrhosis may be complicated by portal HTN which manifests as ascites, congestive splenomegaly/hypersplenism, portosystemic shunts, and hepatorenal syndrome. What is hepatorenal syndrome?
Rapidly developing renal failure in the setting of hepatic cirrhosis
What are some consequences of decreased detoxification in the setting of cirrhosis?
Mental status changes, asterixis, coma (increased serum ammonia)
Gynecomastia, spider angiomata, and palmar erythema (excess estrogen)
Jaundice
What are 2 consequences of decreased protein synthesis in the setting of hepatic cirrhosis?
Hypoalbuminemia
Coagulopathy
3 classic liver changes in alcoholic liver disease
Fatty liver = accumulation of fat in hepatocytes, resulting in heavy greasy liver that resolves with abstinence
Alcoholic hepatitis = direct chemical injury to hepatocytes generally seen with binge drinking; acetaldehyde mediates damage.
Cirrhosis = chronic alcohol-induced liver damage; occurs in 10-20% of alcoholics
Alcoholic hepatitis = direct chemical injury to hepatocytes generally seen with binge drinking; ___________ mediates the damage.
A classic histologic finding is a ______ body, which are composed of damaged _____ _____ within the hepatocytes
Acetaldehyde
Mallory; intermediate filaments
Why is the AST > ALT in alcoholic hepatitis?
AST is a mitochondrial enzyme, and alcohol is a mitochondrial poison, so AST is elevated to a greater extent than ALT
Hemochromatosis may lead to cirrhosis, in which case damage is mediated by generation of ____ ____
Free radicals
Hemochromatosis may be primary or secondary. Primary hemochromatosis is due to mutations in the ____ gene, most commonly ______.
Secondary hemochromatosis is most commonly caused by _____
HFE; C282Y
Transfusions
Hemochromatosis may be suspected if there is brown pigment in hepatocytes. However, lipofuscin is a wear-and-tear pigment that also causes a brown coloration. How is hemosiderin differentiated from lipofuscin in subsequent testing?
Prussian blue stain — will stain the iron deposition, but not lipofuscin
Treatment for hemochromatosis is phlebotomy. These pts are at increased risk for what malignancy?
Hepatocellular carcinoma (due to free radical damage within the liver)
Wilson disease is an autosomal recessive defect in the ______ gene, involved in the ATP-mediated hepatocyte copper transport. This results in lack of copper transport into bile and a lack of copper incorporation into _______
ATP7B; ceruloplasmin
[as a result, copper builds up in hepatocytes, leaks into serum, and deposits in tissues. Copper-mediated production of hydroxyl free radicals leads to tissue damage]
Wilson’s disease presents in childhood with cirrhosis, neurologic manifestations (behavior changes, dementia, chorea, parkinson-like symptoms), Kayser-Fleisher rings in cornea, and increased risk of ________ carcinoma. Treatment is ________ which is a copper chelating agent
Hepatocellular; D-penicillamine
What do labs show in Wilson’s disease including urinary copper, serum ceruloplasmin, and liver biopsy?
Increased urinary copper
Decreased serum ceruloplasmin
Increased copper on liver biopsy
Autoimmune granulomatous destruction of intrahepatic bile ducts; classically arises in women ~age 40 and is associated with other autoimmune diseases. Presents with obstructive jaundice and cirrhosis as a late complication
Primary biliary cirrhosis
Primary biliary cirrhosis is associated with a ________ antibody in the serum
Antimitochondrial
Inflammation and fibrosis of intrahepatic AND extrahepatic bile ducts resulting in PERIDUCTAL fibrosis with onion-skin appearance. Uninvolved regions are dilated resulting in ‘beaded’ appearance on imaging
Primary sclerosing cholangitis
Primary sclerosing cholangitis is associated with the GI condition of _____ _____ and is positive for ___-ANCA.
It presents with obstructive jaundice, cirrhosis is a late complication, and these pts are at increased risk for the malignancy __________
Ulcerative colitis; P-ANCA
Cholangiocarcinoma (cancer of the bile ducts)
Reye syndrome = fulminant liver failure and encephalopathy in children with viral illness who take aspirin. This condition is likely related to _______ damage of hepatocytes.
Patients present with ______ blood glucose, elevated liver enzymes, and nausea with vomiting. It may progress to coma and death
Mitochondrial
Low
Benign tumor of hepatocytes associated with oral contraceptive use (regresses upon cessation of drug); increased risk of rupture and intraperitoneal hemorrhage, especially during pregnancy
Hepatic adenoma
[Note that although benign they carry this feared complication! These are subcapsular tumors, if they rupture through the capsule they cause intraperitoneal hemorrhage]
Major risk factors for hepatocellular carcinoma include chronic hepatitis, cirrhosis, and what fungus-associated cause?
Aflatoxins derived from Aspergillus
Hepatocellular carcinoma loves to invade the ______ vein, which can cause liver infarction secondary to obstruction, aka __________ syndrome. This presents as painful hepatomegaly and ascites
Hepatic v.; Budd-Chiari syndrome
[note that there are other causes of budd-chiari syndrome other than HCC]
Hepatocellular has _____ prognosis
Poor — this is because tumors are often detected late, since symptoms are masked by cirrhosis
Serum tumor marker for HCC
Alpha fetoprotein
Metastasis to the liver is more common than primary tumors and presents with multiple nodules in the liver. Clinically these may be detected as hepatomegaly with nodular free edge of liver.
What are the 4 most common primary sources that metastasize to the liver?
Colon
Pancreas
Lung
Breast
