Gastrointestinal - First Aid Flashcards by Grazielle Verzosa

Normal Gastrointestinal Embryology:

Foregut

esophagus to upper duodenum

How well did you know this?

Not at all

Perfectly

Normal Gastrointestinal Embryology:

Midgut

lower duodenum to proximal 2/3 of transverse colon

How well did you know this?

Not at all

Perfectly

Normal Gastrointestinal Embryology:

Hindgut

distal 1/3 of transverse colon to anal canal above pectinate line

How well did you know this?

Not at all

Perfectly

Normal Gastrointestinal Embryology:

Midgut Development

6th week
- physiologic midgut herniates through umbilical ring
10th week
- returns to abdominal cavity + rotates around superior mesenteric artery (SMA)
- total 270° counterclockwise

How well did you know this?

Not at all

Perfectly

Ventral wall defects are developmental defects due to failure of _____.

rostral fold closure
- sternal defects (ectopia cordis)
lateral fold closure
- omphalocele
- gastroschisis
caudal fold closure
- bladder exstrophy

How well did you know this?

Not at all

Perfectly

Ventral Wall Defects:

extrusion of abdominal contents through abdominal folds (typically right of umbilicus)
not covered by peritoneum or amnion
not associated with chromosome abnormalities

Gastroschisis

The abdominal contents are coming out of the G.

How well did you know this?

Not at all

Perfectly

Ventral Wall Defects:

failure of lateral walls to migrate at umbilical ring → persistent midline herniation of abdominal contents into umbilical cord
surrounded by peritoneum (light gray shiny sac)
associated with congenital anomalies (eg.. trisomies 13 and 18, Beckwith-Wiedemann syndrome) and other structural abnormalities (eg. cardiac, GU, neural tube)

Omphalocele

The abdominal contents are sealed in the O.

How well did you know this?

Not at all

Perfectly

_____ occurs with the failure of umbilical ring to close after physiologic herniation of the intestines. Small defects usually close spontaneously.

Congenital Umbilical Hernia

How well did you know this?

Not at all

Perfectly

Tracheoesophageal Anomalies

Esophageal atresia (EA) with distal tracheoesophageal fistula (TEF) is the most common (85%) and often presents as polyhydramnios in utero (due to inability of fetus to swallow amniotic fluid).
Neonates drool, choke, and vomit with first feeding.
TEFs allow air to enter stomach (visible on CXR).
Cyanosis is 2° to laryngospasm (to avoid reflux-related aspiration).
Clinical Test: failure to pass nasogastric tube into stomach
In H-type, the fistula resembles the letter H.
In pure EA, CXR shows gasless abdomen.

How well did you know this?

Not at all

Perfectly

_____ presents with bilious vomiting and abdominal distension within first 1–2 days of life.

Intestinal Atresia

How well did you know this?

Not at all

Perfectly

Intestinal Atresia:

failure to recanalize
associated with “double bubble” (dilated stomach, proximal duodenum) on x-ray
associated with Down syndrome

Duodenal Atresia

How well did you know this?

Not at all

Perfectly

Intestinal Atresia:

disruption of mesenteric vessels → ischemic necrosis → segmental resorption (bowel discontinuity or “apple peel”)

Jejunal and Ileal Atresia

How well did you know this?

Not at all

Perfectly

GI Pathologies:

most common cause of gastric outlet obstruction in infants (1:600)
palpable olive-shaped mass in the epigastric region, visible peristaltic waves, and nonbilious projectile vomiting at ∼ 2–6 weeks old
more common in firstborn males; associated with exposure to macrolides
results in hypokalemic hypochloremic metabolic alkalosis (2° to vomiting of gastric acid and subsequent volume contraction)
ultrasound shows thickened and lengthened pylorus
treatment is surgical incision (pyloromyotomy)

Hypertrophic Pyloric Stenosis

How well did you know this?

Not at all

Perfectly

Pancreas Embryology

derived from foregut
ventral pancreatic buds contribute to uncinate process and main pancreatic duct
the dorsal pancreatic bud alone becomes the body, tail, isthmus, and accessory pancreatic duct
both the ventral and dorsal buds contribute to pancreatic head

How well did you know this?

Not at all

Perfectly

_____ occurs when abnormal rotation of the ventral pancreatic bud forms a ring of pancreatic tissue → encircles 2nd part of duodenum. May cause duodenal narrowing and vomiting.

Annular Pancreas

How well did you know this?

Not at all

Perfectly

_____ occurs when ventral and dorsal parts fail to fuse at 8 weeks. Common anomaly; mostly asymptomatic, but may cause chronic abdominal pain and/or pancreatitis.

Pancreas Divisum

How well did you know this?

Not at all

Perfectly

Spleen Embryology

arises in mesentery of stomach (hence is mesodermal) but has foregut supply (celiac trunk → splenic artery)

How well did you know this?

Not at all

Perfectly

Retroperitoneal Structures

SAD PUCKER:

Suprarenal (Adrenal) Glands
Aorta and IVC
Duodenum (2nd through 4th parts)
Pancreas (except tail)
Ureters
Colon (descending and ascending)
Kidneys
Esophagus (thoracic portion)
Rectum (partially)

Retroperitoneal structures include GI structures that lack a mesentery and non-GI structures. Injuries to retroperitoneal structures can cause blood or gas
accumulation in retroperitoneal space.

How well did you know this?

Not at all

Perfectly

Important Gastrointestinal Ligaments

How well did you know this?

Not at all

Perfectly

Important Gastrointestinal Ligaments:

connects the liver to the anterior abdominal wall
contains the ligamentum teres hepatis (derivative of fetal umbilical vein) and patent paraumbilical veins
derivative of ventral mesentery

Falciform Ligament

How well did you know this?

Not at all

Perfectly

Important Gastrointestinal Ligaments:

connects the liver to the duodenum
contains the Portal triad:
- proper hepatic artery
- portal vein
- common bile duct
Pringle Maneuver
- ligament may be compressed between the thumb and index finger placed in omental foramen to control bleeding
borders the omental foramen, which connects the greater and lesser sacs
part of the lesser omentum

Hepatoduodenal Ligament

How well did you know this?

Not at all

Perfectly

Important Gastrointestinal Ligaments:

connects the liver to the lesser curvature of the stomach
contains the gastric vessels
separates greater and lesser sacs on the right
may be cut during surgery to access lesser sac
part of the lesser omentum

Gastrohepatic Ligament

How well did you know this?

Not at all

Perfectly

Important Gastrointestinal Ligaments:

connects the greater curvature and the transverse colon
contains the gastroepiploic arteries
part of the greater omentum

Gastrocolic Ligament

How well did you know this?

Not at all

Perfectly

Important Gastrointestinal Ligaments:

connects the greater curvature and the spleen
contains the short gastrics and left gastroepiploic vessels
separates the greater and lesser sacs on the left
part of greater omentum

Gastrosplenic Ligament

How well did you know this?

Not at all

Perfectly

Important Gastrointestinal Ligaments: * connects the spleento the posterior abdominal wall * contains the splenic artery and vein and the tail of the pancreas

Splenorenal Ligament

Digestive Tract Anatomy

Layers of Gut Wall (inside to outside—**MSMS**): * **M**ucosa—epithelium, lamina propria, muscularis mucosa * **S**ubmucosa—includes **S**ubmucosal nerve plexus (Mei**S**sner), **S**ecretes fluid * **M**uscularis Externa—includes **M**yenteric nerve plexus (Auerbach), **M**otility * **S**erosa (when intraperitoneal), Adventitia (when retroperitoneal) Ulcers can extend into submucosa, inner or outer muscular layer. Erosions are in the mucosa only.

Frequencies of Basal Electric Rhythm

slow waves: * Stomach—3 waves/min * Duodenum—12 waves/min * Ileum—8–9 waves/min

Digestive Tract Histology: nonkeratinized stratified squamous epithelium

Esophagus

Digestive Tract Histology: gastric glands

Stomach

Digestive Tract Histology: * villi and microvilli ↑ absorptive surface * Brunner glands (HCO₃⁻-secreting cells of submucosa) and crypts of Lieberkühn (contain stem cells that replace enterocytes/goblet cells and Paneth cells that secrete defensins, lysozyme, and TNF).

Duodenum

Digestive Tract Histology: * plicae circulares (also present in distal duodenum) * crypts of Lieberkühn

Jejunum

Digestive Tract Histology: * Peyer patches (lymphoid aggregates in lamina propria, submucosa) * plicae circulares (proximal ileum) * crypts of Lieberküh * largest number of goblet cells in the small intestine

Ileum

Digestive Tract Histology: * crypts of Lieberkühn but no villi * abundant goblet cells

Colon

Abdominal Aorta and Branches

* Arteries supplying GI structures are single and branch anteriorly. * Arteries supplying non-GI structures are paired and branch laterally and posteriorly. * Two areas of the colon have dual blood supply from distal arterial branches (“watershed regions”) → susceptible in colonic ischemia: * Splenic Flexure—SMA and IMA * Rectosigmoid Junction—the last sigmoid arterial branch from the IMA and superior rectal artery

Gastrointestinal Blood Supply and Innervation: Foregut—Artery

Celiac

Gastrointestinal Blood Supply and Innervation: Foregut—Parasympathetic Innervation

Vagus

Gastrointestinal Blood Supply and Innervation: Foregut—Vertebral Level

T12/L1

Gastrointestinal Blood Supply and Innervation: * Artery—Celiac * Parasympathetic Innervation—Vagus * Vertebral Level—T12/L1 * pharynx (vagus nerve only) and lower esophagus (celiac artery only) to proximal duodenum; liver, gallbladder, pancreas, spleen (mesoderm)

Foregut

Gastrointestinal Blood Supply and Innervation: Midgut—Artery

SMA

Gastrointestinal Blood Supply and Innervation: Midgut—Parasympathetic Innervation

Vagus

Gastrointestinal Blood Supply and Innervation: Midgut—Vertebral Level

Gastrointestinal Blood Supply and Innervation: * Artery—SMA * Parasympathetic Innervation—Vagus * Vertebral Level—L1 * distal duodenum to proximal 2/3 of transverse colon

Midgut

Gastrointestinal Blood Supply and Innervation: Hindgut—Artery

IMA

Gastrointestinal Blood Supply and Innervation: Hindgut—Parasympathetic Innervation

Pelvic

Gastrointestinal Blood Supply and Innervation: Hindgut—Vertebral Level

Gastrointestinal Blood Supply and Innervation: * Artery—IMA * Parasympathetic Innervation—Pelvic * Vertebral Level—L3 * distal 1/3 of transverse colon to upper portion of rectum

Hindgut

Celiac Trunk

* Branches: * common hepatic * splenic * left gastric * The branches constitute the main blood supply of the stomach. * Strong anastomoses exist between: * left and right gastroepiploics * left and right gastrics * Posterior duodenal ulcers penetrate gastroduodenal artery causing hemorrhage. * Anterior duodenal ulcers perforate into the anterior abdominal cavity, potentially leading to pneumoperitoneum.

Portosystemic Anastomoses

Sites of Anastamosis (Portal ↔ Systemic): ① Esophagus * esophageal varices * left gastric ↔ azygos ② Umbilicus * caput medusae * paraumbilical ↔ small epigastric veins of the anterior abdominal wall ③ Rectum * anorectal varices * superior rectal ↔ middle and inferior rectal Varices of **gut**, **butt**, and **caput** (medusae) are commonly seen with portal hypertension. ④Treatment with a transjugular intrahepatic portosystemic shunt (TIPS) between the portal vein and hepatic vein relieves portal hypertension by shunting blood to the systemic circulation, bypassing the liver. Can precipitate hepatic encephalopathy.

Pectinate (Dentate) Line

* Formed where endoderm (hindgut) meets ectoderm. * Above * adenocarcinoma * internal hemorrhoids—receive visceral innervation and are therefore not painful * Below * anal fissures * squamous cell carcinoma * external hemorrhoids—receive somatic innervation (inferior rectal branch of pudendal nerve) and are therefore painful if thrombosed

\_\_\_\_\_ is a tear in the anal mucosa below the pectinate line. Pain while pooping; blood on toilet Paper. Located posteriorly becaus this area is poorly perfused. Associated with low-fiber diets and constipation.

Anal Fissure * **P**ectinate line * **P**ain while **P**ooping * blood on toilet **P**aper * **P**osterior * **P**oorly **P**erfused

Liver Tissue Architecture

* The functional unit of the liver is made up of hexagonally arranged lobules surrounding the central vein with portal triads on the edges (consisting of a portal vein, hepatic artery, bile ducts, as well lymphatics). * Apical surface of hepatocytes faces bile canaliculi. * Basolateral surface faces sinusoids. * Kupffer cells, which are specialized macrophages, are located in the sinusoids. * Hepatic stellate (Ito) cells in space of Disse store vitamin A (when quiescent) and produce extracellular matrix (when activated). Responsible for hepatic fibrosis.

Liver Tissue Zones

Zone I—periportal zone: * affected 1st by viral hepatitis * ingested toxins (eg. cocaine) Zone II—intermediate zone: * yellow fever Zone III—pericentral vein (centrilobular) zone: * afected 1st by ischemia * high concentration of cytochrome P-450 * most sensitive to metabolic toxins (eg. ethanol, CCl4, halothane, rifampin) * site of alcoholic hepatitis

Biliary Structures

* Gallstones that reach the confluence of the common bile and pancreatic ducts at the ampulla of Vater can block both the common bile and pancreatic ducts (_Double Duct sign_), causing both cholangitis and pancreatitis, respectively. * Tumors that arise in head of pancreas (usually ductal adenocarcinoma) can cause obstruction of common bile duct → enlarged gallbladder with painless jaundice (_Courvoisier sign_). * Cholangiography shows filling defects in the gallbladder and cystic duct.

Femoral Region

You go from **lateral to medial** to find your **NAV**e**L** * **N**erve * **A**rtery * **V**ein * **L**ymphatics Femoral Triangle * contains femoral nerve, artery, and vein Femoral Sheath * fascial tube 3–4 cm below inguinal ligament * contains femoral vein, artery, and canal (deep inguinal lymph nodes) but not femoral nerve

Inguinal Canal

\_\_\_\_ are protrusion of peritoneum through an opening, usually at a site of weakness. Contents may be at risk for incarceration (not reducible back into abdomen/pelvis) and strangulation (ischemia and necrosis). Complicated cases can present with tenderness, erythema, fever.

Hernias

Diaphragmatic Hernia

* Abdominal structures enter the thorax. * May occur due to congenital defect of pleuroperitoneal membrane or from trauma. * Commonly occurs on left side due to relative protection of right hemidiaphragm by liver. * Most commonly a hiatal hernia, in which stomach herniates upward through the esophageal hiatus of the diaphragm. * Sliding Hiatal Hernia * gastroesophageal junction is displaced upward as gastric cardia slides into hiatus * “hourglass stomach” * most common type * Paraesophageal Hiatal Hernia * gastroesophageal junction is usually normal but gastric fundus protrudes into the thorax

Indirect Inguinal Hernia

* Goes through the internal (deep) inguinal ring, external (superficial) inguinal ring, and into the scrotum. * Enters internal inguinal ring lateral to inferior epigastric vessels. * Caused by failure of processus vaginalis to close (can form hydrocele). * May be noticed in infants or discovered in adulthood. * Much more common in males. * An indirect inguinal hernia follows the path of descent of the testes. * Covered by all 3 layers of spermatic fascia. **MD**s don’t **LI**e. * **M**edial to inferior epigastric vessels = **D**irect hernia * **L**ateral to inferior epigastric vessels = **I**ndirect hernia

Direct Inguinal Hernia

* Protrudes through the inguinal (Hesselbach) triangle. * Bulges directly through parietal peritoneum medial to the inferior epigastric vessels but lateral to the rectus abdominis. * Goes through the external (superficial) inguinal ring only. * Covered by external spermatic fascia. * Usually occurs in older men due to an acquired weakness in the transversalis fascia. **MD**s don’t **LI**e. * **M**edial to inferior epigastric vessels = **D**irect hernia * **L**ateral to inferior epigastric vessels = **I**ndirect hernia

Femoral Hernia

* Protrudes below inguinal ligament through femoral canal below and lateral to pubic tubercle. * More common in females, but overall inguinal hernias are the most common. * More likely to present with incarceration or strangulation than inguinal hernias.

Inguinal (Hesselbach) Triangle:

* Inferior Epigastric Vessels * Lateral Border of Rectus Abdominis * Inguinal Ligament

Gastrointestinal Regulatory Substances: * G cells (antrum of stomach, duodenum) * ↑ gastric H+ secretion * ↑ growth of gastric mucosa * ↑ gastric motility * ↑ by stomach distention/alkalinization, amino acids, peptides, vagal stimulation via gastrin-releasing peptide (GRP) * ↓ by pH \< 1.5 * ↑ by chronic PPI use * ↑ in chronic atrophic gastritis (eg. *H. pylori*) * ↑↑ in Zollinger-Ellison syndrome (gastrinoma)

Gastrin

Gastrointestinal Regulatory Substances: * D cells (pancreatic islets, GI mucosa) * ↓ gastric acid and pepsinogen secretion * ↓ pancreatic and small intestine fluid secretion * ↓ gallbladder contraction * ↓ insulin and glucagon release * ↑ by acid * ↓ by vagal stimulation * inhibits secretion of various hormones (encourages somato-stasis) * Octreotide is an analog used to treat acromegaly, carcinoid syndrome, and variceal bleeding.

Somatostatin

Gastrointestinal Regulatory Substances: * I cells (duodenum, jejunum) * ↑ pancreatic secretion * ↑ gallbladder contraction * ↓ gastric emptying * ↑ sphincter of Oddi relaxation * ↑ by fatty acids, amino acids * acts on neural muscarinic pathways to cause pancreatic secretion

Cholecystokinin

Gastrointestinal Regulatory Substances: * S cells (duodenum) * ↑ pancreatic HCO₃^– secretion * ↓ gastric acid secretion * ↑ bile secretion * ↑ by acid, fatty acids in lumen of duodenum * ↑ HCO₃^– neutralizes gastric acid in duodenum, allowing pancreatic enzymes to function

Secretin

Gastrointestinal Regulatory Substances: * K cells (duodenum, jejunum) * Exocrine: ↓ gastric H+ secretion * Endocrine: ↑ insulin release * ↑ by fatty acids, amino acids, and oral glucose * also known as Gastric Inhibitory Peptide (GIP) * oral glucose load leads to ↑ insulin compared to IV equivalent due to GIP secretion

Glucose-Dependent Insulinotropic Peptide

Gastrointestinal Regulatory Substances: * small intestine * produces migrating motor complexes (MMCs) * ↑ in fasting state * _____ receptor agonists (eg. erythromycin) are used to stimulate intestinal peristalsis

Motilin

Gastrointestinal Regulatory Substances: * parasympathetic ganglia in sphincters, gallbladder, and small intestine * ↑ intestinal water and electrolyte secretion * ↑ relaxation of intestinal smooth muscle and sphincters * ↑ by distention and vagal stimulation * ↓ by adrenergic input

Vasoactive Intestinal Polypeptide VIPoma—non-α, non-β islet cell pancreatic tumor that secretes VIP. Causes **W**atery **D**iarrhea, **H**ypokalemia, and **A**chlorhydria (**WDHA** syndrome).

Gastrointestinal Regulatory Substances: * ↑ smooth muscle relaxation, including lower esophageal sphincter (LES) * loss of secretion is implicated in ↑ LES tone of achalasia

Nitric Oxide

Gastrointestinal Regulatory Substances: * stomach * ↑ appetite * ↑ in fasting state * ↓ by food * ↑ in Prader-Willi syndrome * ↓ after gastric bypass surgery

Ghrelin

Gastrointestinal Secretory Products: * parietal cells (stomach) * Vitamin B12–binding protein (required for B12 uptake in terminal ileum) * autoimmune destruction of parietal cells → chronic gastritis and pernicious anemia

Intrinsic Factor

Gastrointestinal Secretory Products: * parietal cells (stomach) * ↓ stomach pH * ↑ by histamine, vagal stimulation (ACh), and gastrin * ↓ by somatostatin, GIP, prostaglandin, and secretin

Gastric Acid

Gastrointestinal Secretory Products: * chief cells (stomach) * protein digestion * ↑ by vagal stimulation (ACh), and local acid

Pepsin * Pepsinogen (inactive) is converted to Pepsin (active) in the presence of H⁺.

Gastrointestinal Secretory Products: * mucosal cells (stomach, duodenum, salivary glands, pancreas) and Brunner glands (duodenum) * neutralizes acid * ↑ by pancreatic and biliary secretion with secretin * trapped in mucus that covers the gastric epithelium

Bicarbonate

Locations of Gastrointestinal Secretory Cells

Gastrin ↑ acid secretion primarily through its effects on enterochromaffin-like (ECL) cells (leading to histamine release) rather than through its direct effect on parietal cells.

Pancreatic secretions are \_\_\_\_\_.

Isotonic * low flow → high Cl⁻ * high flow → high HCO₃⁻

Pancreatic Secretions: * starch digestion * secreted in active form

α-amylase

Pancreatic Secretions: fat digestion

Lipases

Pancreatic Secretions: * protein digestion * includes trypsin, chymotrypsin, elastase, and carboxypeptidases * secreted as proenzymes also known as zymogens

Proteases

Pancreatic Secretions: * converted to active enzyme trypsin → activation of other proenzymes and cleaving of additional trypsinogen molecules into active trypsin (positive feedback loop) * converted to trypsin by enterokinase/enteropeptidase, a brush-border enzyme on duodenal and jejunal mucosa

Trypsinogen

Carbohydrate Absorption

* Only monosaccharides (glucose, galactose, fructose) are absorbed by enterocytes. * Glucose and galactose are taken up by SGLT1 (Na⁺ dependent). * **F**ructose is taken up via **F**acilitated diffusion by GLUT**5**. * All are transported to blood by GLUT2. * D-Xylose Absorption Test: distinguishes GI mucosal damage from other causes of malabsorption

Vitamin/Mineral Absorption: absorbed as Fe²⁺ in the duodenum

Iron

Vitamin/Mineral Absorption: absorbed in the small bowel

Folate

Vitamin/Mineral Absorption: * absorbed in the terminal ileum along with bile salts * requires intrinsic factor

Vitamin B12

GI Physioology: * unencapsulated lymphoid tissue found in the lamina propria and submucosa of ileum * contain specialized M cells that sample and present antigens to immune cells * B cells stimulated in germinal centers of _____ differentiate into IgA-secreting plasma cells, which ultimately reside in the lamina propria * IgA receives protective secretory component and is then transported across the epithelium to the gut to deal with intraluminal antigen

Peyer Patches **I**ntra-**g**ut **A**ntibody

Bile Composition

* bile salts * bile acids conjugated to glycine or taurine, making them water soluble * phospholipids * cholesterol * bilirubin * water * ions

\_\_\_\_\_ catalyzes rate‑limiting step of bile acid synthesis.

Cholesterol 7α-Hydroxylase

Bile Functions

* digestion and absorption of lipids and fat-soluble vitamins * cholesterol excretion (body’s 1° means of eliminating cholesterol) * antimicrobial activity (via membrane disruption) ↓ absorption of enteric bile salts at distal ileum (as in short bowel syndrome, Crohn disease) prevents normal fat absorption. Calcium, which normally binds oxalate, binds fat instead, so free oxalate is absorbed by gut → ↑ frequency of calcium oxalate kidney stones.

Bilirubin

* Heme is metabolized by heme oxygenase to biliverdin, which is subsequently reduced to bilirubin. * Unconjugated bilirubin is removed from blood by liver, conjugated with glucuronate, and excreted in bile. * Direct Bilirubin * conjugated with glucuronic acid * water soluble * Indirect Bilirubin * unconjugated * water insoluble

GI Pathologies: * stone(s) in salivary gland duct * can occur in 3 major salivary glands (parotid, submandibular, sublingual) * single stones are more common in the submandibular gland (Wharton duct) * presents as recurrent pre-/periprandial pain and swelling in affected gland * caused by dehydration or trauma * treated conservatively with NSAIDs, gland massage, warm compresses, and sour candies (to promote salivary flow)

Sialolithiasis

GI Pathologies: inflammation of salivary gland due to obstruction, infection, or immune-mediated mechanisms

Sialadenitis

GI Pathologies: * 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

Salivary Gland Tumors

Salivary Gland Tumors: * most common salivary gland tumor * composed of chondromyxoid stroma and epithelium and recurs if incompletely excised or ruptured intraoperatively * may undergo malignant transformation

Pleomorphic Adenoma (Benign Mixed Tumor)

Salivary Gland Tumors: * most common malignant tumor * has mucinous and squamous components

Mucoepidermoid Carcinoma

Salivary Gland Tumors: * benign cystic tumor with germinal center * typically found in smokers * bilateral in 10% * multifocal in 10%

Warthin Tumor (Papillary Cystadenoma Lymphomatosum) **War**riors from **Germ**any love **smoking**.

GI Pathologies: * failure of the 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 → progressive dysphagia to solids and liquids (vs. obstruction—solids only) * barium swallow shows dilated esophagus with an area of distal stenosis (“bird’s beak”) * associated with ↑ risk of esophageal cancer * 2° _____ (pseudo\_\_\_\_\_) may arise from Chagas disease (*T. cruzi* infection) or extraesophageal malignancies (mass effect or paraneoplastic)

Achalasia A-chalasia = absence of relaxation.

Esophageal Pathologies: * 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

Boerhaave Syndrome

Esophageal Pathologies: * 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

Eosinophilic Esophagitis

Esophageal Pathologies: associated with caustic ingestion and acid reflux

Esophageal Strictures

Esophageal Pathologies: * dilated submucosal veins in the lower 1 ⁄3 of esophagus 2° to portal hypertension * common in cirrhotics * may be source of life-threatening hematemesis

Esophageal Varices

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

Esophagitis

Esophageal Pathologies: * commonly presents as heartburn, regurgitation, and dysphagia * may also present as chronic cough and hoarseness (laryngopharyngeal reflux) * associated with asthma * transient decreases in LES tone

Gastroesophageal Reflux Disease (GERD)

Esophageal Pathologies: * partial-thickness mucosal lacerations at gastroesophageal junction due to severe vomiting * often presents with hematemesis * usually found in alcoholics and bulimics

Mallory-Weiss Syndrome

Esophageal Pathologies: * triad of dysphagia, iron deficiency anemia, and esophageal webs * may be associated with glossitis * increased risk of esophageal squamous cell carcinoma

Plummer-Vinson Syndrome Plumbers **DIE**. * **D**ysphagia * **I**ron deficiency anemia * **E**sophageal webs

Esophageal Pathologies: * esophageal smooth muscle atrophy → ↓ LES pressure and dysmotility → acid reflux and dysphagia → stricture, Barrett esophagus, and aspiration * part of CREST syndrome

Sclerodermal Esophageal Dysmotility

Esophageal Pathologies: * specialized intestinal metaplasia * replacement of nonkeratinized stratified squamous epithelium with intestinal epithelium (nonciliated columnar with goblet cells) in distal esophagus * due to chronic gastroesophageal reflux disease (GERD) * associated with ↑ risk of esophageal adenocarcinoma

Barrett Esophagus

Esophageal cancer typically presents with _____ and has poor prognosis.

* progressive dysphagia (first solids, then liquids) * weight loss

Esophageal Cancer: * upper 2/3 * alcohol, hot liquids, caustic strictures, smoking, achalasia * more common worldwide

Squamous Cell Carcinoma

Esophageal Cancer: * lower 1/3 * chronic GERD, Barrett esophagus, obesity, smoking, achalasia * more common in America

Adenocarcinoma

Gastritis: * erosions can be caused by: * NSAIDs—↓ PGE2 → ↓ gastric mucosa protection * burns (Curling ulcer)—hypovolemia → mucosal ischemia * brain injury (Cushing ulcer)—↑ vagal stimulation → ↑ ACh → ↑ H+ production * common among alcoholics and patients taking daily NSAIDs (eg. patients with rheumatoid arthritis)

Acute Gastritis

Gastritis: * caused by burns * hypovolemia → mucosal ischemia

Curling Ulcer **Burn**ed by the **Curling** iron.

Gastritis: * caused by brain injury * ↑ vagal stimulation → ↑ ACh → ↑ H+ production

Cushing Ulcer Always **Cush**ion the **brain**.

Gastritis: * mucosal inflammation * often leading to atrophy (hypochlorhydria → hypergastrinemia) and intestinal metaplasia (↑ risk of gastric cancers)

Chronic Gastritis

Chronic Gastritis: * most common * ↑ risk of peptic ulcer disease and MALT lymphoma * affects antrum first and spreads to body of stomach

*H. pylori*

Chronic Gastritis: * autoantibodies to parietal cells and intrinsic factor * ↑ risk of pernicious anemia * affects body/fundus of stomach

Autoimmune

GI Pathologies: * hyperplasia of gastric mucosa → hypertrophied rugae (look like brain gyri) * causes excess mucus production with resultant protein loss and parietal cell atrophy with ↓ acid production * precancerous * presents with epigastric pain, anorexia, weight loss, vomiting, and edema (due to protein loss)

Ménétrier Disease

GI Pathologies: * most commonly 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

Gastric Cancer

Gastric Cancer: * associated with *H. pylori*, dietary nitrosamines (smoked foods), tobacco smoking, achlorhydria, and chronic gastritis * commonly on lesser curvature * looks like ulcer with raised margins

Intestinal

Gastric Cancer: * not associated with *H. pylori* * signet ring cells—mucin-filled cells with peripheral nuclei * stomach wall grossly thickened and leathery (linitis plastica)

Diffuse

Gastric Cancer: involvement of left supraclavicular node by metastasis from stomach

Virchow Node

Gastric Cancer: * bilateral metastases to ovaries * bundant mucin-secreting, signet ring cells

Krukenberg Tumor

Gastric Cancer: subcutaneous periumbilical metastasis

Sister Mary Joseph Nodule

Peptic Ulcer Disease: * pain can be greater with meals—weight loss * *H. pylori* in ~ 70% * ↓ mucosal protection against gastric acid * caused by NSAIDs * ↑ risk for carcinoma * biopsy margins to rule out malignancy

Gastric Ulcer

Peptic Ulcer Disease: * pain decreases with meals—weight gain * H. pylori in ~ 90% * ↓ mucosal protection against gastric acid or ↑ gastric acid secretion * caused by Zollinger-Ellison syndrome * generally benign * hypertrophy of Brunner glands

Duodenal Ulcer

Ulcer Complications: * gastric, duodenal (posterior \> anterior) * most common complication * ruptured gastric ulcer on the lesser curvature of stomach → bleeding from left gastric artery * ulcer on the posterior wall of duodenum → bleeding from gastroduodenal artery

Hemorrhage

Ulcer Complications: * pyloric channel * duodenal

Obstruction

Ulcer Complications: * duodenal (anterior \> posterior) * may see free air under diaphragm with referred pain to the shoulder via irritation of phrenic nerve

Perforation

Malabsorption syndromes can cause \_\_\_\_\_.

* diarrhea * steatorrhea * weight loss * weakness * vitamin and mineral deficiencies

Malabsorption syndromes are screened with \_\_\_\_\_.

fecal fat (eg. Sudan stain)

Malabsorption Syndromes

* Celiac Disease * Lactose Intolerance * Pancreatic Insufficiency * Tropical Sprue * Whipple Disease

Malabsorption Syndromes: * gluten-sensitive enteropathy, celiac sprue * autoimmune-mediated intolerance of gliadin (gluten protein found in wheat) → malabsorption and steatorrhea * associated with HLA-DQ2, HLA-DQ8, northern European descent, dermatitis herpetiformis, ↓ bone density

Celiac Disease

Malabsorption Syndromes: * IgA anti-tissue transglutaminase (IgA tTG), anti-endomysial, anti-deamidated gliadin peptide antibodies * villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis * moderately ↑ risk of malignancy (eg. T-cell lymphoma) * ↓ mucosal absorption primarily affects distal duodenum and/or proximal jejunum

Celiac Disease

Malabsorption Syndromes: * passively absorbed in proximal small intestine * blood and urine levels ↓ with mucosa defects or bacterial overgrowth * normal in pancreatic insufficiency

D-Xylose Test

Malabsorption Syndromes: Celiac Disease Treatment

gluten-free diet

Malabsorption Syndromes: * lactase deficiency * normal-appearing villi, except when 2° to injury at tips of villi (eg. viral enteritis) * osmotic diarrhea with ↓ stool pH (colonic bacteria ferment lactose) * Lactose Hydrogen Breath Test: ⊕ for lactose malabsorption if post-lactose breath hydrogen value rises \> 20 ppm compared with baseline

Lactose Intolerance

Malabsorption Syndromes: * due to chronic pancreatitis, cystic fibrosis, or obstructing cancer * causes malabsorption of fat and fat-soluble vitamins (A, D, E, K) as well as vitamin B12 * ↓ duodenal pH (bicarbonate) and fecal elastase

Pancreatic Insufficiency

Malabsorption Syndromes: * 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 * ↓ mucosal absorption affecting duodenum and jejunum but can involve ileum with time * associated with megaloblastic anemia due to folate deficiency and, later, B12 deficiency

Tropical Sprue

Malabsorption Syndromes: * infection with *Tropheryma whipplei* (intracellular gram ⊕) * PAS ⊕ foamy macrophages in intestinal lamina propria and mesenteric nodes * cardiac symptoms, arthralgias, and neurologic symptoms are common * diarrhea/steatorrhea occur later in disease course * most common in older men

Whipple Disease **Foamy Whipp**ed cream in a **CAN**: * **C**ardiac symptoms * **A**rthralgias * **N**eurologic symptoms

Inflammatory Bowel Disease

* Crohn Disease * Ulcerative Colitis

Crohn Disease: Location

* any portion of the GI tract * usually the terminal ileum and colon * skip lesions * rectal sparing

Crohn Disease: Gross Morphology

* transmural inflammation → fistulas * cobblestone mucosa * creeping fat * bowel wall thickening (“string sign” on barium swallow x-ray) * linear ulcers * fissures

Crohn Disease: Microscopic Morphology

Crohn Disease: Complications

* malabsorption/malnutrition * colorectal cancer (↑ risk with pancolitis) * fistulas (eg. enterovesical fistulae, which can cause recurrent UTI and pneumaturia) * phlegmon/abscess * strictures (causing obstruction) * perianal disease

Crohn Disease: Intestinal Manifestation

diarrhea that may or may not be bloody

Crohn Disease: Extraintestinal Manifestations

* rash (pyoderma gangrenosum, erythema nodosum) * eye inflammation (episcleritis, uveitis) * oral ulcerations (aphthous stomatitis) * arthritis (peripheral, spondylitis) * kidney stones (usually calcium oxalate) * gallstones * may be ⊕ for anti-*Saccharomyces cerevisiae* antibodies (ASCA)

Crohn Disease: Treatment

* Corticosteroids * Azathioprine * Antibiotics (eg. Ciprofloxacin, Metronidazole) * Infliximab * Adalimumab

Crohn Disease: Findings

A **fat gran**ny and an old **crone** (Chron) **skip** down a **cobblestone** road away from the **wreck**. * creeping **fat** * noncaseating **gran**ulomas * **skip** leasions * **cobblestone** mucosa * **rec**tal sparing

Ulcerative Colitis: Location

* colitis = colon inflammation * continuous colonic lesions * always with rectal involvement

Ulcerative Colitis: Gross Morphology

* mucosal and submucosal inflammation only * friable mucosa with superficial and/or deep ulcerations * loss of haustra → “lead pipe” appearance on imaging

Ulcerative Colitis: Microscopic Morphology

* crypt abscesses and ulcers * bleeding * no granulomas * Th2 mediated

Ulcerative Colitis: Complications

* malabsorption/malnutrition * colorectal cancer (↑ risk with pancolitis) * fulminant colitis * toxic megacolon * perforation

Ulcerative Colitis: Intestinal Manifestation

bloody diarrhea

Ulcerative Colitis: Extraintestinal Manifestations

* rash (pyoderma gangrenosum, erythema nodosum) * eye inflammation (episcleritis, uveitis) * oral ulcerations (aphthous stomatitis) * arthritis (peripheral, spondylitis) * 1° sclerosing cholangitis * associated with p-ANCA

Ulcerative Colitis: Treatment

* 5-Aminosalicylic preparations (eg. Mesalamine) * 6-Mercaptopurine * Infliximab * Colectomy

Ulcerative Colitis: Findings

**ULCCCERS**: * **U**lcers * **L**arge intestine * **C**ontinuous, **C**olorectal carcinoma, **C**rypt abscesses * **E**xtends proximally * **R**ed diarrhea * **S**clerosing cholangitis

GI Pathologies: * recurrent abdominal pain associated with ≥ 2 of the following: * related to defecation * change in stool frequency * change in form (consistency) of stool * no structural abnormalities * most common in middle-aged women * chronic symptoms may be diarrhea-predominant, constipation-predominant, or mixed * pathophysiology is multifaceted * first-line treatment is lifestyle modification and dietary changes

Irritable Bowel Syndrome

GI Pathologies: * acute inflammation of the appendix, can be due to obstruction by fecalith (in adults) or lymphoid hyperplasia (in children) * initial diffuse periumbilical pain migrates to McBurney point (1 ⁄3 the distance from right anterior superior iliac spine to umbilicus) * nausea, fever * may perforate → peritonitis * may elicit psoas, obturator, and Rovsing signs, guarding and rebound tenderness on exam. * Differentials: * diverticulitis (elderly) * ectopic pregnancy (use β-hCG to rule out) * pseudoappendicitis

Appendicitis

Diverticula of the GI Tract: * 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”

Diverticulum

Diverticula of the GI Tract: all gut wall layers outpouch (eg. Meckel)

“True” Diverticulum

Diverticula of the GI Tract: * only mucosa and submucosa outpouch * occur especially where vasa recta perforate muscularis externa

“False” Diverticulum or Pseudodiverticulum

Diverticula of the GI Tract: * many false diverticula of the colon, commonly sigmoid * common (in ~ 50% of people \> 60 years) * caused by ↑ intraluminal pressure and focal weakness in colonic wall * associated with obesity and diets low in fiber, high in total fat/red meat * often asymptomatic or associated with vague discomfort * Complications include diverticular bleeding * (painless hematochezia), diverticulitis.

Diverticulosis

Diverticula of the GI Tract: * inflammation of diverticula with wall thickening classically causing LLQ pain, fever, and leukocytosis * treat with antibiotics * Complications: * abscess * fistula (colovesical fistula → pneumaturia), obstruction (inflammatory stenosis), perforation (→ peritonitis)

Diverticulitis

Diverticula of the GI Tract: * 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

Zenker Diverticulum **Elder MIKE** has **bad breath**. * **Elder**ly * **M**ales * **I**nferior pharyngeal constrictor * **K**illian triangle * **E**sophageal dysmotility * **Halitosis**

Diverticula of the GI Tract: * 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

Meckel Diverticulum 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)

GI Pathologies: * 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 ↑ with Down syndrome * explosive expulsion of feces (squirt sign) → empty rectum on digital exam * diagnosed by absence of ganglionic cells on rectal suction biopsy

Hirschsprung disease

GI Pathologies: * anomaly of midgut rotation during fetal development → improper positioning of bowel (small bowel clumped on the right side) * formation of fibrous bands (Ladd bands) * can lead to volvulus, duodenal obstruction

Malrotation

GI Pathologies: * 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

Volvulus

GI Pathologies: * 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 * utrasound 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)

Intussusception

GI Pathologies: * 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

Acute Mesenteric Ischemia

GI Pathologies: * “intestinal angina” * atherosclerosis of celiac artery, SMA, or IMA → intestinal hypoperfusion → postprandial epigastric pain → food aversion and weight loss

Chronic Mesenteric Ischemia

GI Pathologies: * 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

Colonic Ischemia

GI Pathologies: * 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

Angiodysplasia

GI Pathologies: * 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

Adhesion

GI Pathologies: * intestinal hypomotility without obstruction → constipation and ↓ flatus distended/tympanic * abdomen with ↓ bowel sounds * associated with abdominal surgeries, opiates, hypokalemia, and sepsis * Treatment: * bowel rest * electrolyte correction * cholinergic drugs (stimulate intestinal motility)

Ileus

GI Pathologies: in cystic fibrosis, meconium plug obstructs intestine, preventing stool passage at birth

Meconium Ileus

GI Pathologies: * 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, and portal venous gas

Necrotizing Enterocolitis

GI Pathologies: * 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

Colonic Polyps

Colonic Polyps: Non-Neoplastic

* Hamartomatous Polyps * Mucosal Polyps * Inflammatory Pseudopolyps * Submucosal Polyps * Hyperplastic Polyps

Colonic Polyps: * non-neoplastic * solitary lesions do not have significant risk of transformation * growths of normal colonic tissue with distorted architecture * associated with Peutz-Jeghers syndrome and juvenile polyposis

Hamartomatous Polyps

Colonic Polyps: * non-neoplastic * small, usually \< 5 mm * look similar to normal mucosa * clinically insignificant

Mucosal Polyps

Colonic Polyps: * non-neoplastic * due to mucosal erosion in inflammatory bowel disease

Inflammatory Pseudopolyps

Colonic Polyps: * non-neoplastic * may include lipomas, leiomyomas, fibromas, and other lesions

Submucosal Polyps

Colonic Polyps: * non-neoplastic * most common * generally smaller and predominantly located in rectosigmoid region * occasionally evolves into serrated polyps and more advanced lesions

Hyperplastic Polyps

Colonic Polyps: Malignant Potential

* Adenomatous Polyps * Serrated Polyps

Colonic Polyps: * malignant potential * 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

Adenomatous Polyps

Colonic Polyps: * malignant potential * 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

Serrated Polyps

Polyposis Syndromes

* Familial Adenomatous Polyposis * Gardner Syndrome * Turcot Syndrome * Peutz-Jeghers Syndrome * Juvenile Polyposis Syndrome

Polyposis Syndromes: * 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

Familial Adenomatous Polyposis

Polyposis Syndromes: * FAP + osseous and soft tissue tumors * congenital hypertrophy of retinal pigment epithelium * impacted/supernumerary teeth

Gardner Syndrome

Polyposis Syndromes: FAP/Lynch syndrome + malignant CNS tumor (eg. medulloblastoma, glioma)

Turcot Syndrome

Polyposis Syndromes: * autosomal dominant syndrome featuring numerous hamartomas throughout GI tract, along with hyperpigmented mouth, lips, hands, genitalia * associated with ↑ risk of breast and GI cancers (eg. colorectal, stomach, small bowel, pancreatic)

Peutz-Jeghers Syndrome

Polyposis Syndromes: * autosomal dominant syndrome in children (typically \< 5 years old) featuring numerous hamartomatous polyps in the colon, stomach, small bowel * associated with ↑ risk of CRC

Juvenile Polyposis Syndrome

GI Pathologies: * 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

Lynch Syndrome

Colorectal Cancer

* 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 * Rectosigmoid \> Ascending \> Descending Colon * 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).

Colorectal Cancer 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

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.

Cirrhosis and Portal Hypertension

_Cirrhosis_ * diffuse bridging fibrosis (via stellate cells) and regenerative nodules disrupt normal architecture of live * ↑ risk for hepatocellular carcinoma (HCC) * etiologies include alcohol, nonalcoholic steatohepatitis, chronic viral hepatitis, autoimmune hepatitis, biliary disease, and genetic/metabolic disorders _Portal Hypertension_ * ↑ pressure in portal venous system * etiologies include cirrhosis (most common cause in Western countries), vascular obstruction (eg. portal vein thrombosis, Budd-Chiari syndrome), and schistosomiasis

GI Pathologies: * 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)

Spontaneous Bacterial Peritonitis

Serum Markers of Liver Pathology: Enzymes Released in Liver Damage

* Aspartate Aminotransferase * Alanine Aminotransferase * Alkaline Phosphatase * γ-Glutamyl Transpeptidase

Serum Markers of Liver Pathology: * released in liver damage * ↑ in most liver disease * ↑ in alcoholic liver disease

Aspartate Aminotransferase Alanine Aminotransferase * ↑ in most liver disease: ALT \> AST * ↑ in alcoholic liver disease: AST \> ALT * AST \> ALT in nonalcoholic liver disease suggests progression to advanced fibrosis or cirrhosis

Serum Markers of Liver Pathology: * released in liver damage * ↑ in cholestasis (eg. biliary obstruction), infiltrative disorders, and bone disease

Alkaline Phosphatase

Serum Markers of Liver Pathology: * released in liver damage * ↑ in various liver and biliary diseases (just as ALP can), but not in bone disease * associated with alcohol use

γ-Glutamyl Transpeptidase

Serum Markers of Liver Pathology: Functional Liver Markers

* Bilirubin * Albumin * Prothrombin Time * Platelets

Serum Markers of Liver Pathology: * functional liver marker * ↑ in various liver diseases (eg. biliary obstruction, alcoholic or viral hepatitis, cirrhosis) and hemolysis

Bilirubin

Serum Markers of Liver Pathology: * functional liver marker * ↓ in advanced liver disease (marker of liver’s biosynthetic function)

Albumin

Serum Markers of Liver Pathology: * functional liver marker * ↑ in advanced liver disease (↓ production of clotting factors, thereby measuring the liver’s biosynthetic function)

Prothrombin Time

Serum Markers of Liver Pathology: * functional liver marker * ↓ in advanced liver disease (↓ thrombopoietin, liver sequestration) and portal hypertension (splenomegaly/splenic sequestration)

Platelets

GI Pathologies: * 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 ↓ β-oxidation by reversible inhibition of mitochondrial enzymes * avoid aspirin in children, except in those with Kawasaki disease

Reye Syndrome **Reye** of sun**SHINE**: * **S**teatosis of liver/hepatocytes * **H**ypoglycemia/**H**epatomegaly * **I**nfection (VZV, influenza) * **N**ot awake (coma) * **E**ncephalopathy

Alcoholic Liver Disease: macrovesicular fatty change that may be reversible with alcohol cessation

Hepatic Steatosis

Alcoholic Liver Disease: * requires sustained, long-term consumption * swollen and necrotic hepatocytes with neutrophilic infiltration * Mallory Bodies (intracytoplasmic eosinophilic inclusions of damaged keratin filaments) * AST \> ALT (ratio usually \> 2:1)

Alcoholic Hepatitis Make a to**AST** with alcohol.

Alcoholic Liver Disease: * 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

Alcoholic Cirrhosis

GI Pathologies: * 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

Nonalcoholic Fatty Liver Disease A**L**T \> AST (**L**ipids)

Hepatic Encephalopathy

* cirrhosis → portosystemic shunts → ↓ NH₃ metabolism → neuropsychiatric dysfunction * reversible neuropsychiatric dysfunction ranging from disorientation/asterixis (mild) to difficult arousal or coma (severe) * Triggers: * ↑ NH₃ production and absorption (due to dietary protein, GI bleed, constipation, infection) * ↓ NH₃ removal (due to renal failure, diuretics, bypassed hepatic blood flow post-TIPS) * Treatment: * Lactulose (↑ NH₄ + generation) * Rifaximin or Neomycin (↓ NH₃ producing gut bacteria)

GI Pathologies: * 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, and 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: * ↑ α-fetoprotein * ultrasound or contrast CT/MRI * biopsy

Hepatocellular Carcinoma/Hepatoma

GI Pathologies: * most common benign liver tumor * typically occurs at age 30–50 years * biopsy contraindicated because of risk of hemorrhage

Cavernous Hemangioma

GI Pathologies: * rare, benign liver tumor, often related to oral contraceptive or anabolic steroid use * may regress spontaneously or rupture (abdominal pain and shock)

Hepatic Adenoma

GI Pathologies: * malignant tumor of endothelial origin * associated with exposure to arsenic and vinyl chloride

Angiosarcoma

GI Pathologies: * most common overall liver tumor * from GI malignancies, breast and lung cancer * rarely solitary

Metastases

GI Pathologies: * thrombosis or compression of hepatic veins with centrilobular congestion and necrosis → congestive liver disease (hepatomegaly, ascites, varices, abdominal pain, liver failure) * absence of JVD * associated with hypercoagulable states, polycythemia vera, postpartum state, HCC * may cause nutmeg liver (mottled appearance)

Budd-Chiari Syndrome

GI Pathologies: * 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 the lungs, ↓ α1-antitrypsin → uninhibited elastase in alveoli → ↓ elastic tissue → panacinar emphysema

α1-Antitrypsin Deficiency

\_\_\_\_\_ is the abnormal yellowing of the skin and/or sclera due to bilirubin deposition. Hyperbilirubinemia 2° to ↑ production or ↓ disposition (impaired hepatic uptake, conjugation, excretion).

Jaundice

Common causes of ↑ bilirubin levels include \_\_\_\_\_.

HOT Liver: * **H**emolysis * **O**bstruction * **T**umor * **L**iver disease

Hyperbilirubinemia: Unconjugated (Indirect) Hyperbilirubinemia

* Hemolytic, * Physiologic (newborns) * Crigler-Najjar Syndrome * Gilbert Syndrome

Hyperbilirubinemia: Conjugated (Direct) Hyperbilirubinemia

* Biliary Tract Obstruction: * gallstones * cholangiocarcinoma * pancreatic or liver cancer * liver fluke * Biliary Tract Disease: * 1° sclerosing cholangitis * 1° biliary cholangitis * Excretion Defect: * Dubin-Johnson Syndrome * Rotor Syndrome

Hyperbilirubinemia: Mixed (Direct and Indirect) Hyperbilirubinemia

* Hepatitis * Cirrhosis

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. * Treated with phototherapy (non-UV) which isomerizes unconjugated bilirubin to water-soluble form.

Hereditary Hyperbilirubinemias are all \_\_\_\_\_.

Autosomal Recessive

Hereditary Hyperbilirubinemias: * autosomal recessive * mildly ↓ UDP-glucuronosyltransferase conjugation and impaired bilirubin uptake * asymptomatic or mild jaundice usually with stress, illness, or fasting * ↑ unconjugated bilirubin without overt hemolysis * relatively common, benign condition

Gilbert Syndrome ① **G**o! (asymptomatic/benign)

Hereditary Hyperbilirubinemias: * autosomal recessive * absent UDP-glucuronosyltransferase * presents early in life * patients die within a few years * Findings: * jaundice * kernicterus (bilirubin deposition in brain) * ↑ unconjugated bilirubin * Treatment: * plasmapheresis * phototherapy * liver transplant is curative

Crigler-Najjar Syndrome, Type I ② **N**o-go! (symptomatic) \*Type II is less severe and responds to Phenobarbital, which ↑ liver enzyme synthesis.

Hereditary Hyperbilirubinemias: * autosomal recessive * conjugated hyperbilirubinemia due to defective liver excretion * grossly black liver * benign

Dubin-Johnson Syndrome ③ **D**ark liver

Hereditary Hyperbilirubinemias: * autosomal recessive * is similar to Dubin-Johnson syndrome, but milder in presentation without black liver * due to impaired hepatic uptake and excretion

Rotor syndrome **R**egular liver

GI Pathologies: * autosomal recessive mutations in hepatocyte copper-transporting ATPase (ATP7B gene; chromosome 13) → ↓ copper incorporation into apoceruloplasmin and excretion into bile → ↓ serum ceruloplasmin * copper accumulates, especially in liver, brain, cornea, kidneys * ↑ 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, and renal disease (eg. Fanconi syndrome) * Treatment: * chelation with penicillamine or trientine * oral zinc

Wilson Disease (Hepatolenticular Degeneration)

GI Pathologies: * autosomal recessive * C282Y mutation \> H63D mutation on HFE gene, located on chromosome 6 * associated with HLA-A3 * leads to abnormal iron sensing and ↑ intestinal absorption (↑ ferritin, ↑ iron, ↓ TIBC → ↑ 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

Hemochromatosis

GI Pathologies: * presents after age 40 when total body iron \> 20 g * iron loss through menstruation slows progression in women * classic triad of cirrhosis, diabetes mellitus, and skin pigmentation (“_bronze diabetes_”) * also causes restrictive cardiomyopathy (classic) or dilated cardiomyopathy (reversible), hypogonadism, arthropathy (calcium pyrophosphate deposition; especially metacarpophalangeal joints) * HCC is the common cause of death

Hemochromatosis

Hemochromatosis is treated with \_\_\_\_\_.

* Repeated Phlebotomy * Dhelation * Deferasirox * Deferoxamine * Oral Deferiprone

GI Pathologies: * may present with pruritus, jaundice, dark urine, light-colored stool, and hepatosplenomegaly * typically with cholestatic pattern of LFTs (↑ conjugated bilirubin, ↑ cholesterol, ↑ ALP)

Biliary Tract Disease

Biliary Tract Disease: * unknown cause of concentric “onion skin” bile duct fibrosis → alternating strictures and dilation with “beading” of intra- and extrahepatic bile ducts on ERCP and magnetic resonance cholangiopancreatography (MRCP) * classically in middle-aged men with IBD * associated with ulcerative colitis * p-ANCA ⊕ * ↑ IgM * can lead to 2° biliary cholangitis * ↑ risk of cholangiocarcinoma and gallbladder cancer

Primary Sclerosing Cholangitis

Biliary Tract Disease: * autoimmune reaction → lymphocytic infiltrate + granulomas → destruction of lobular bile ducts * classically in middle-aged women * anti-mitochondrial antibody ⊕, * ↑ IgM * associated with other autoimmune conditions (eg. Sjögren syndrome, Hashimoto thyroiditis, CREST, rheumatoid arthritis, celiac disease)

Primary Biliary Cholangitis

Biliary Tract Disease: * extrahepatic biliary obstruction → ↑ pressure in intrahepatic ducts ↑ injury/ fibrosis and bile stasis * patients with known obstructive lesions (gallstones, biliary strictures, pancreatic carcinoma) * may be complicated by ascending cholangitis

Secondary Biliary Cholangitis

GI Pathologies: * caused by ↑ cholesterol and/or bilirubin, ↓ bile salts, and gallbladder stasis * ↑ risk in females, obese, multipara and ≥ 40 y.o. * most common complication is cholecystitis * can also cause acute pancreatitis and ascending cholangitis * diagnose with ultrasound * treat with elective cholecystectomy if symptomatic

Gallstones (Cholelithiasis) Risk Factors (**4 F**’s): * **F**emale * **F**at * **F**ertile (multiparity) * **F**orty

Gallstones (Cholelithiasis): * 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

Biliary Colic

Gallstones (Cholelithiasis): * presence of gallstone(s) in common bile duct * leads to elevated ALP, GGT, direct bilirubin, and/or AST/ALT

Choledocholithiasis

Gallstones (Cholelithiasis): acute or chronic inflammation of gallbladder

Cholecystitis

Cholecystitis: * most common type * due to gallstone impaction in the cystic duct resulting in inflammation and gallbladder wall thickening * can produce 2° infection

Calculous Cholecystitis

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) * ↑ 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

Acalculous Cholecystitis

Cholecystitis: * fistula between gallbladder and GI tract → stone enters GI lumen → obstructs at ileocecal valve (narrowest point) * can see air in biliary tree (pneumobilia)

Gallstone Ileus

Gallstones (Cholelithiasis): * calcified gallbladder due to chronic cholecystitis * usually found incidentally on imaging * treated with prophylactic cholecystectomy due to high rates of gallbladder cancer (mostly adenocarcinoma)

Porcelain Gallbladder

Gallstones (Cholelithiasis): * infection of biliary tree usually due to obstruction that leads to stasis/bacterial overgrowth * _Charcot Triad_: * jaundice * fever * RUQ pain * _Reynolds Pentad_: * Charcot Triad * altered mental status * shock (hypotension)

Ascending Cholangitis

GI Pathologies: * autodigestion of pancreas by pancreatic enzymes * Diagnosis by 2 of 3 Criteria: * acute epigastric pain often radiating to the back * ↑ serum amylase or lipase (more specific) to 3× upper limit of normal * characteristic imaging findings * Complications: * pseudocyst (lined by granulation tissue, not epithelium) * abscess, necrosis * hemorrhage * infection * organ failure (ARDS, shock, renal failure) * hypocalcemia (precipitation of Ca²⁺ soaps)

Acute Pancreatitis

Causes of Acute Pancreatitis

**I GET SMASHED**: * **I**diopathic * **G**allstones * **E**thanol * **T**rauma * **S**teroids * **M**umps * **A**utoimmune disease * **S**corpion sting * **H**ypercalcemia/**H**ypertriglyceridemia (\> 1000 mg/dL) * **E**RCP * **D**rugs (eg. sulfa drugs, NRTIs, protease inhibitors)

GI Pathologies: * chronic inflammation, atrophy, calcification of the pancreas * major causes include alcohol abuse and genetic predisposition (ie. cystic fibrosis) * can be idiopathic * complications include pancreatic insufficiency and pseudocysts * pancreatic insufficiency (typically when \<10% pancreatic function) may manifest with steatorrhea, fat-soluble vitamin deficiency, and diabetes mellitus * amylase and lipase may or may not be elevated (almost always elevated in acute pancreatitis)

Chronic Pancreatitis

GI Pathologies: * very aggressive tumor arising from pancreatic ducts (disorganized glandular structure with cellular infiltration) * often metastatic at presentation, with average survival ~ 1 year after diagnosis * tumors more common in pancreatic head (obstructive jaundice) * associated with CA 19-9 tumor marker (also CEA, less specific) * ↑ risk with tobacco use, chronic pancreatitis (especially \> 20 years), diabetes, \> 50 y.o., Jewish and African-American males * Findings: * abdominal pain radiating to back * weight loss (due to malabsorption and anorexia) * Migratory Thrombophlebitis—redness and tenderness on palpation of extremities (_Trousseau Syndrome_) * obstructive jaundice with palpable, nontender gallbladder (_Courvoisier Sign_) * Treatment: * Whipple procedure * chemotherapy * radiation therapy

Pancreatic Adenocarcinoma

Acid Suppression Therapy

Acid Suppression Therapy: Histamine-2 Blockers

**Dine** on a table for **2**: * Cimeti**dine** * Raniti**dine** * Famoti**dine** * Nizati**dine**

Acid Suppression Therapy: * reversible block of histamine H₂-receptors → ↓H⁺ secretion by parietal cells * used for peptic ulcer, gastritis, and mild esophageal reflux

Histamine-2 Blockers

Acid Suppression Therapy: * histamine-2 blocker * potent inhibitor of cytochrome P-450 (multiple drug interactions) * also has antiandrogenic effects (prolactin release, gynecomastia, impotence, ↓ libido in males) * can cross blood-brain barrier (confusion, dizziness, headaches) and placenta * ↓ renal excretion of creatinine

Cimetidine

Acid Suppression Therapy: * histamine-2 blocker * ↓ renal excretion of creatinine

* Cimetidine * Ranitidine

Acid Suppression Therapy: Proton Pump Inhibitors

* Omeprazole * Lansoprazole * Esomeprazole * Pantoprazole * Dexlansoprazole

Acid Suppression Therapy: * irreversibly inhibit H⁺/K⁺ ATPase in stomach parietal cells * used for peptic ulcer, gastritis, esophageal reflux, Zollinger-Ellison syndrome, component of therapy for *H. pylori*, and stress ulcer prophylaxis * ↑ risk of *C. difficile* infection, pneumonia, and acute interstitial nephritis * ↓ serum Mg²⁺ with long-term use * ↓ serum Mg²⁺ and ↓ Ca²⁺ absorption (potentially leading to increased fracture risk in elderly)

Proton Pump Inhibitors

Acid Suppression Therapy: * can affect absorption, bioavailability, or urinary excretion of other drugs by altering gastric and urinary pH or by delaying gastric emptying * all can cause hypokalemia * overuse can also cause the following problems

Antacids

Antacids: * constipation and hypophosphatemia * proximal muscle weakness * osteodystrophy * seizures

Aluminum Hydroxide Alu**minimum** amount of feces.

Antacids: * hypercalcemia (milk-alkali syndrome) * rebound acid ↑ * can chelate and ↓ effectiveness of other drugs (eg. tetracycline)

Calcium Carbonate

Antacids: * diarrhea * hyporeflexia * hypotension * cardiac arrest

Magnesium Hydroxide **Mg²**⁺ = **m**ust **g**o **to** the bathroom

Acid Suppression Therapy: * bind to ulcer base, providing physical protection and allowing HCO₃^– secretion to reestablish pH gradient in the mucous layer * require acidic environment * usually not given with PPIs/H2 blockers * ↑ ulcer healing * used for travelers’ diarrhea

* Bismuth * Sucralfate

Acid Suppression Therapy: * PGE1 analog * ↑ production and secretion of gastric mucous barrier * ↓ acid production * prevention of NSAID-induced peptic ulcers (NSAIDs block PGE1 production) * also used off-label for induction of labor (ripens cervix) * causes diarrhea * contraindicated in women of childbearing potential (abortifacient)

Misoprostol

GI Drugs: * long-acting somatostatin analog * inhibits secretion of various splanchnic vasodilatory hormones * used for acute variceal bleeds, acromegaly, VIPoma, and carcinoid tumors * causes nausea, cramps, and steatorrhea * ↑ risk of cholelithiasis due to CCK inhibition

Octreotide

GI Drugs: * a combination of sulfapyridine (antibacterial) and 5-aminosalicylic acid (anti-inflammatory) * activated by colonic bacteria * used for ulcerative colitis and Crohn disease (colitis component) * causes malaise, nausea, sulfonamide toxicity, and reversible oligospermia

Sulfasalazine

GI Drugs: * agonist at μ-opioid receptors * slows gut motility * poor CNS penetration (low addictive potential) * used for diarrhea * causes constipation and nausea

Loperamide

GI Drugs: * 5-HT3 antagonist * ↓ vagal stimulation * powerful central-acting antiemetic * control vomiting postoperatively and in patients undergoing cancer chemotherapy * causes headache, constipation, QT interval prolongation, and serotonin syndrome

Ondansetron

GI Drugs: * D2 receptor antagonist * ↑ resting tone, contractility, LES tone, motility, promotes gastric emptying * does not influence colon transport time * used in diabetic and postsurgery gastroparesis, antiemetic therapy, and persistent GERD * causes ↑ parkinsonian effects, tardive dyskinesia, restlessness, drowsiness, fatigue, depression, and diarrhea * drug interaction with digoxin and diabetic agents * contraindicated in patients with small bowel obstruction or Parkinson disease (due to D2-receptor blockade)

Metoclopramide

GI Drugs: * inhibits gastric and pancreatic lipase → ↓ breakdown and absorption of dietary fats * used for eight loss * causes abdominal pain, flatulence, and bowel urgency/frequent bowel movements * ↓ absorption of fat-soluble vitamins

Orlistat

GI Drugs: indicated for constipation or patients on opiates requiring a bowel regimen

Laxatives

Laxatives: * soluble fibers draw water into gut lumen, forming a viscous liquid that promotes peristalsis * causes bloating

Bulk-Forming Laxatives: * Psyllium * Methylcellulose

Laxatives: * provides osmotic load to draw water into GI lumen * causes diarrhea and dehydration * may be abused by bulimics

Osmotic Laxatives * Magnesium Hydroxide * Magnesium Citrate * Polyethylene Glycol * Lactulose * treats hepatic encephalopathy * gut flora degrade lactulose into metabolites (lactic acid, acetic acid) that promote nitrogen excretion as NH₄⁺

Laxatives: * enteric nerve stimulation * → colonic contraction * causes diarrhea and melanosis coli

Stimulants * Senna

Laxatives: * promotes incorporation of water and fat into stool * causes diarrhea

Emollients * Docusate

GI Drugs: * substance P antagonist * blocks NK1 (neurokinin-1) receptors in brain * used as an antiemetic for chemotherapy-induced nausea and vomiting

Aprepitant

Gastrointestinal - First Aid Flashcards

(277 cards)