Gastrointestinal Flashcards Preview

USMLE Step 1. > Gastrointestinal > Flashcards

Flashcards in Gastrointestinal Deck (146):
1

GI embryo - foregut, midgut, hindgut

Foregut - pharynx to duodenum

Midgut - duodenum to proximal 2/3 of transverse colon

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

2

Developmental defects of anterior abdominal wall due to failure of:

Rostral fold closure - sternal defects

Lateral fold closure - omphalocele, gastroschisis

Caudal fold closure - bladder exstrophy

3

Duodenal atresia

Failure to recanalize (trisomy 21)

4

Jejunal, ileal, colonic atresia

Due to vascular accident (apple peel atresia)

5

Midgut development

6th week - midgut herniates through umbilical ring

10th week - returns to abdominal cavity + rotates around superior mesenteric artery (SMA)

6

Gastroschisis

extrusion of abdominal contents through abdominal folds; not covered by peritoneum

7

Omphalocele

Persistence of herniation of abdominal contents into umbilical cord, sealed by peritoneum

8

Tracheoesophageal anomalies

Esophageal atresia (EA) with distal tracheoesophageal fistula (TEF) is the most common (85%)

Results in drooling, choking, and vomiting with first feeding. TEF allows air to enter stomach (visible on CXR). Cyanosis is secondary 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 the CXR shows gasless abdomen

9

Congenital pyloric stenosis

Hypertrophy of the pylorus causes obstruction. Palpable "olive" mass in epigastric region and nonbilious projectile vomiting at about 2-6 weeks old. Occurs in 1/600 live births, more often in firstborn males.

Results in hypokalemic hypochloremic metabolic alkalosis (secondary to vomiting of gastric acid and subsequent volume contraction). Treatment is surgical incision (pyloromyotomy)

10

Pancreas and spleen embryo

Pancreas - 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 the pancreatic head.

Annular pancreas - ventral pancreatic bud abnormally encircles 2nd part of duodenum; forms a ring of pancreatic tissue that may cause duodenal narrowing

Pancreatic divisum - ventral and dorsal parts fail to fuse at 8 weeks. Common anomly; mostly asymptomatic, but may cause chronic abdominal pain and/or pancreatitis

Spleen - arises in mesentery of stomach (hence is mesodermal) but is supplied by foregut (celiac artery)

11

Retroperitoneal structures

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

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)

12

Falciform ligament

Connects liver to anterior abdominal wall

Contains:
Ligamentum teres hepatis (derivate of fetal umbilical vein)

Derivative of ventral mesentery

13

Hepatoduodenal ligament

Connects liver to duodenum

Contains:
Portal triad - proper hepatic artery, portal vein, common bile duct

Pringle maneuver - ligament may be compressed between thumb and index finger placed in omental foramen to control bleeding

Borders the omental foramen, which connects the greater and lesser sacs

14

Gastrohepatic ligament

Connects liver to lesser curvature of stomach

Contains:
Gastric arteries

Separates greater and lesser sacs on the right.

May be cut during surgery to access liver sac

15

Gastrocolic ligament

Connects greater curvature and transverse colon

Contains:
Gastroepiploic arteries

Part of grater omentum

16

Gastrosplenic ligament

Connects greater curvature to spleen

Contains:
Short gastrics
Left gastrorpiploic vessels

Separates greater and lesser sacs on the left

17

Splenorenal

Connects spleen to posterior abdominal wall

Contains:
Splenic artery and vein
Tail of pancreas

18

Layers of gut wall

MSMS

Mucosa - epithelium, lamina, propria, muscularis mucosa

Submucosa - includes Submucosal nerve plexus (Meissner), Secretes fluid

Muscularis externa - include Myenteric plexus (Auerbach), Motility

Serosa (when intraperitoneal), adventitia (when retroperitoneal)

Frequencies of basal electric rhythm (slow waves)
Stomach - 3 waves/min
Duodenum - 12 waves/min
Ileum - 8-9 waves/min

19

Digestive tract histology

Esophagus - Nonkeratinized stratified squamous epithelium

Stomach - gastric glands

Duodenum - Villi and microvilli increase absorptive surface
Brunner glands (HCO3 secreting cells of submucosa) and crypts of Lieberkuhn

Jejunum - Plicae circulares and crypts of Lieberkuhn

Ileum - Peyer patches (lymphoid aggregates in lamina propria, submucosa), plicae circulares (proximal ileum), and crypts of Liberkuhn. Largest number of goblet cells in the SI

Colon - Colon has crypts of Lieberkuhn but no villi; abundant goblet cells

20

Superior mesenteric artery syndrome

When the transverse portion (third part) of duodenum is entrapped between SMA and aorta, causing intestinal obstruction

21

GI blood supply and innervation

1) Foregut embryologic origin

Celiac Artery
Vagus Nerve (parasymp)
Vertebral level = T12/L1

Pharynx (Vagus only) and lower esophagus (celiac artery only) to proximal duodenum; liver, gallbladder, pancreas, spleen (mesoderm)

2) Midgut

SMA
Vagus (parasymp)
L1

Distal duodenum to proximal 2/3 of transverse colon

3) Hindgut

IMA
Pelvic (parasymp)
L3

Distal 1/3 of transverse colon to upper portion of rectum; splenic flexure is a watershed region between SMA and IMA

22

Celiac trunk

Branches of celiac trunk = Common hepatic, splenic, and Left Gastric. These constitute the main blood supply of the stomach

Short gastrics have poor anastomoses if splenic artery is blocked.

Strong anastomoses exist between:
L and R gastroepiploics
L and R gastrics

23

Portosystemic anastomoses

1) Esophagus - Esophageal varices

L gastric vein and esophageal vein

2) Umbilicus - Caput medusae

Paraumbilical veins - small epigastric veins of the anterior abdominal wall

3) Rectum - Anorectal varices (NOT internal hemorrhoids)

Superior rectal vein - middle and inferior rectal veins

Varices of gut, butt, and caput are commonly seen with portal HTN

Treatment with a transjugular intrahepatic portosystemic shunt (TIPS) between the portal vein and hepatic vein relieves portal HTN by shunting blood to the systemic circulation bypassing the liver

24

Pectinate (Dentate) line

Formed where endoderm (hindgut) meets ectoderm

1) Above pectinate line - internal hemorrhoids, adenocarcinoma

Arterial supply from superior rectal artery (branch of IMA)

Venous drainage: superior rectal vein - inferior mesenteric vein - portal system

Internal hemorrhoids receive visceral innervation and are therefore NOT PAINFUL

Lymphatic drainage to internal iliac lymph nodes

2) Below pectinate line - external hemorrhoids, anal fissures, squamous cell carcinoma

Arterial supply from inferior rectal artery (branch of internal pudendal artery)

Venous drainage: inferior rectal vein - internal pudendal vein - internal iliac vein - common iliac vein - IVC

External hemorrhoids receives somatic innervation (inferior rectal branch of pudendal nerve) and are therefore PAINFUL if thrombosed

Lymphatic drainage to superficial inguinal nodes

Anal fissure - tear in the anal mucosa below the Pectinate line: Pain while Pooping; blood on "toilet" Paper. Located Posteriorly since this area is Poorly Perfused

25

Liver anatomy

Apical surface of hepatocytes faces bile canaliculi. Basolateral surface faces sinusoids

Zone 1 - periportal zone
- affected 1st by viral hepatitis
- ingested toxins (cocaine)

Zone 2 - intermediate zone
- Yellow Fever

Zone 3 - pericentral vein (centrilobar) zone
- Affected 1st by ischemia
- Contains cytochrome P-450 system
- Most sensitive to metabolic toxins
- Site of alcoholic hepatitis

26

Femoral region

Organization - Lateral to Medial: Nerve-Artery-Vein-Empty space-Lymphatics

You go from lateral to medial to find your NAVEL

Femoral triangle - Contains femoral vein, artery, nerve
Venous near the penis

Femoral sheath - fascial tube 3-4 cm below inguinal ligament. Contains femoral vein, artery, and canal (deep inguinal lymph nodes) but not femoral nerve

27

Biliary structures - stones

Gallstones that reach the confluence of the common bile duct 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 can cause obstruction of common bile duct alone leads to painless jaundice

28

Diaphragmatic hernia

Abdominal structures enter the thorax; may occur due to congenital defect of pleuroperitoneal membrane, or as a result of 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 - most common. Gastroesophageal junction is displaced upward; "hourglass stomach"

Paraesophageal hernia - gastroesophageal junction is usually normal. Fundus protrudes into the thorax

29

Indirect inguinal hernia

Goes through internal (deep) inguinal ring, external (superficial) inguinal ring, and into the scrotum. Enters internal inguinal rung lateral to inferior epigastric artery.

Occurs in infants owing to failure of precessus vaginalis to close (can form hydrocele). 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

30

Direct inguinal hernia

Protrudes through the inguinal (Hasselbach) triangle. Bulges directly through abdominal wall medial to inferior epigastric artery. Goes through the external (superficial) inguinal ring only. Covered by external spermatic fascia. Usually in older men

MDs dont LIe

Medial to inferior epigastric artery = Direct
Lateral to inferior epigastric artery = Indirect

31

Femoral hernia

Protrudes below inguinal ligament through femoral canal below and lateral to pubic tubercle. More common in females

Leading cause of bowel incarceration

32

Hasselbach triangle

Inferior epigastric vessels
Lateral border of rectus abdominis
Inguinal ligament

33

Gastrin

1) Source:
G cells (antrum of stomach, duodenum)

2) Action:
Increases gastric H secretion (lower pH)
Increases growth of gastric mucosa
Increases gastric mucosa

3) Regulation:
Increased by stomach distention/alkalinization, amino acids, peptides, vagal stimulation

Decreased by pH

34

Somatostatin

1) Source:
D cells (pancreatic islets, GI mucosa)

2) Action:
Decreased gastric acid and pepsinogen secretion
Decreased pancreatic and SI fluid secretion
Decreased gallbladder contraction
Decreased insulin and glucagon release

3) Regulation:
Increased by acid
Decreased by vagal stimulation

4) Notes:
Inhibits secretion of GH, insulin, and other hormones (encourages somato-stasis).
Octreotide is an analog used to treat acromegaly, insulinoma, carcinoid syndrome, and variceal bleeding

35

Cholecystokinin

1) Source:
I cells (duodenum, jejunum)

2) Action:
Increases pancreatic secretion
Increases gallbladder contraction
Decreases gastric emptying
Increases sphincter of Oddi relaxation

3) Regulation:
Increased by fatty acids, amino acids

4) Notes:
CCK acts on neural muscarinic pathways to cause pancreatic secretion

36

Secretin

1) Source:
S cells (duodenum)

2) Action:
Increases pancreatic HCO3 secretion
Decreases gastric acid secretion
Increases bile secretion

3) Regulation:
Increased by acid, fatty acids in lumen of duodenum

4) Notes:
Increased HCO3 neutralizes gastric acid in duodenum, allowing pancreatic enzymes to function

37

Glucose-dependent insulinotropic peptide (GIP)

1) Source:
K cells (duodenum, jejunum)

2) Action:
Exocrine - Lowers gastric H secretion
Endocrine - Increases insulin release

3) Regulation:
Increased by fatty acids, amino acids, oral glucose

4) Notes:
Also known as gastric inhibitory peptide

Oral glucose load leads to increased insulin compared to IV equivalent due to GIP secretion

38

Motilin

1) Source:
Small intestine

2) Action:
Produces migrating motor complexes (MMCs)

3) Regulation:
Increased in fasting state

4) Notes:
Motilin receptor agonists (erythromycin) are used to stimulate intestinal peristalsis

39

Vasoactive intestinal polypeptide (VIP)

1) Source:
Parasympathetic ganglia in sphincters, gallbladder, small intestine

2) Action:
Increases intestinal water and electrolyte secretion
Increases relaxation of intestinal smooth muscle and sphincters

3) Regulation:
Increased by distention and vagal stimulation
Decreased by adrenergic input

4) Notes:

VIPoma - non alpha, non B islet cell pancreatic tumor that secretes VIP

Copious Watery Diarrhea, Hypokalemia, and Achlorhydria (WDHA syndrome)

40

Nitric Oxide

1) Source:

2) Action:
Increases smooth muscle relaxation, including lower esophageal sphincter (LES)

3) Regulation:

4) Notes:
Loss of NO secretion is implicated in increased LES tone of achalasia

41

Intrinsic factor

1) Source:
Parietal cells (stomach)

2) Action:
Vitamin B12-binding protein (required for B12 uptake in terminal ileum)

3) Regulation:


4) Notes:
Autoimmune destruction of parietal cells leads to chronic gastritis and pernicious anemia

42

Gastric acid

1) Source:
Parietal cells (stomach)

2) Action:
Lowers stomach pH

3) Regulation:
Increased by histamine, ACh, gastrin
Decreased by somatostatin, GIP, prostaglandin, secretin

4) Notes:
Gastrinoma: gastrin-secreting tumor that causes high levels of acid and ulcers refractory to medical therapy (like PPIs)

43

Pepsin

1) Source:
Chief cells (stomach)

2) Action:
Protein digestion

3) Regulation:
Increased by vagal stimulation, local acid

4) Notes:
Pepsinogen (inactive) is converted to pepsin (active) in the presence of H

44

HCO3

1) Source:
Mucosal cells (stomach, duodenum, salivary glands, pancreas) and Brunner glands (duodenum)

2) Action:
Neutralizes acid

3) Regulation:
Increased by pancreatic and biliary secretion with secretin

4) Notes:
HCO3 is trapped in mucus that covers the gastric epithelium

45

Pancreatic secretions - general

Isotonic fluid; low flow - high Cl, high flow - high HCO3

46

a-amylase

Pancreatic secretion

Role: Starch digestion

Secreted in active form

47

Lipases

Pancreatic secretion

Role: Fat digestion

48

Proteases

Pancreatic secretion

Role: Protein digestion

Includes trypsin, chymotrypsin, elastase, carboxypeptidases

Secreted as proenzymes also known as zymogens

49

Trypsinogen

Pancreatic secretion

Role: 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 duodenal and jejunal mucosa

50

Carbohydrate absorption

Only monosaccharides (glucose, galactose, fructose) are absorbed by enterocytes

Glucose and galactose are taken up by SGLT1 (Na dependent). Fructose is taken up by facilitated diffusion by GLUT-5. All are transported to blood by GLUT-2

D-xylose absorption test: distinguishes GI mucosal damage from other causes of malabsorption

51

Vitamin/Mineral absorption

Iron - absorbed as Fe in duodenum

Folate - absorbed in small bowel

B12 - absorbed in terminal ileum, along with bile salts, requires intrinsic factor

IFB = Iron First Bro

Clinically relevant in patients with small bowel disease or after resection

52

Peyer patches

Unencapsulated lymphoid tissue found in 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 Peyer patches differentiate into IgA-secreting plasma cells, which ultimately reside in lamina propria. IgA receives protective secretory component and is then transported across the epithelium to the gut to deal with intraluminal antigen

Think of IgA, the Intra-Gut-Antibody. And always say "secretory IgA"

53

Bile

Composed of bile salts (bile acids conjugated to glycine or taurine, making them water soluble), phospholipids, cholesterol, bilirubin, water, and ions. Cholesterol 7a-hydroxylase catalyzes rate-limiting step of bile synthesis

Functions:
Digestion and absorption of lipids and fat-soluble vitamins
Cholesterol excretion (body's only means of eliminating cholesterol)
Antimicrobial activity (via membrane disruption)

54

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

55

Salivary gland tumors

Generally benign – in parotid gland

1) Pleomorphic adenoma: (benign mixed tumor) – most common.

Presents as painless, mobile mass. Made of chondromyxoid stroma and epithelium and recurs if incompletely excised or ruptured during surgery.

2) Mucoepidermoid carcinoma: most common malignant tumor. Has mucous and Squamous parts. Painless, slow growing mass.

3) Warthin tumor (papillary cystadenoma lymphomatosum): benign cystic tumor with germinal centers

56

Achalasia

(absence of relaxation): Failure of relaxation of LES due to loss of myenteric plexus. High LES resting pressure and uncoordinated peristalsis – progressive dysphagia to solids and liquids (vs obstruction – solid only).

Ba swallow shows dilated esophagus with an area of distal stenosis. Associated with higher risk of esophageal squamous cell carcinoma. “Birds beak” on Ba swallow.

Secondary achalasia = can come from chagas disease (T. Cruzi infection) or Malignancies (mass effect or paraneoplastic)

57

Boerhaave Symdrome

Esophageal

Transmural, usually distal esophageal with pneumomediastinum due to violent retching; surgical emergency

58

Eosinophilic esophagitis

Infiltration of eosinophils in the esophagus in atopic patients. Food allergens - dysphagia, heartburn, strictures. Unresponsive to GERD therapy

59

Esophageal strictures

Associated with lye ingestion and acid reflux

60

Esophageal varices

Dilated submucosal veins in lower 1/3 of esophagus secondary to portal HTN.

Common in alcoholics, may be source of upper GI bleeding

61

Esophagitis

Associated with reflux, infection in immunocompromised (Candida: white pseudomembrane, HSV-1: punched-out ulcers, CMV: linear ulcers) or chemical ingestion

62

Gastroesophageal reflux disease

GERD

Commonly presents as heartburn and regurgitation upon lying down. May also present with nocturnal cough and dyspnea, adult-onset asthma. Decrease in LES tone

63

Mallory-Weiss syndrome

Mucosal lacerations at the gastroesophageal junction due to severe vomiting. Leads to hematemesis. Usually found in alcoholics and bulimics.

64

Plummer-Vinson Syndrome

Triad of: Dysphagia, Iron deficiency anemia, Esophageal Webs

"DIE"

May be associated with glossitis. Increased risk of esophageal squamous cell carcinoma (Plumbers DIE)

65

Sclerodermal esophageal dysmotility

Esophageal smooth muscle atrophy leads to lower LES pressure and dysmotility. This causes acid reflux and dysphagia leading to stricture, Barrett esophagus, and aspiration. Part of CREST syndrome

66

Barrett esophagus

Glandular metaplasia - replacement of nonkeratinized stratified squamous epithelium with intestinal epithelium (nonciliated columnar with goblet cells) in distal esophagus.

Due to chronic acid reflux (GERD). Associated with esophagitis, esophageal ulcers, and increased risk of esophageal adenocarcinoma

67

Esophageal cancer

Can be squamous cell carcinoma or adenocarcinoma. Typically presents with progressive dysphagia (first solid, then liquids) and weight loss; poor prognosis. Risk factors are AABCDEFFGH

Achalasia
Alcohol - Squamous
Barrett esophagus - adeno
Cigarettes - both
Diverticula (Zenker) - squamous
Esophageal web - squamous
Familial
Fat (obesity) - adeno
GERD - adeno
Hot liquids - squamous

Worldwide, squamous cell is more common.

Adenocarcinoma is most common type in America

Squamous cell - upper 2/3
Adenocarcinoma - lower 1/3

68

Acute gastritis (erosive)

Disruption of mucosal barrier leading to inflammation

Can be caused by:
1) NSAIDs - lower PGE2 leading to lower gastric mucosa protection

2) Burns (Curling ulcer) - lower plasma volume - sloughing of gastric mucosa

3) Brain injury (Cushing ulcer) - increased vagal stimulation leads to increased ACh which raises H production

Especially common among alcoholics and patients taking daily NSAIDs (patients with RA)

"Burned by a curling iron"

"Always cushion the brain"

69

Chronic gastritis (nonerosive)

1) Type A (fundus/body) - Autoimmune disorder characterized by Autoantibodies to parietal cells, pernicious Anemia, and Achlorhydria. Associated with other autoimmune disorders

2) Type B (antrum) - Most common type. Caused by H Pylori infection. Increased risk of MALT lymphoma

A comes before B

A = autoimmune = first part of stomach

B = bacteria = second part of stomach (antrum)

70

Menetrier Disease

Gastric hyperplasia of mucosa leading to hypertrophied rugae, excess mucus production with resultant protein loss and parietal cell atrophy with decreased acid production.

Precancerous.

Rugae of stomach are so hypertrophied that they look like brain gyri

71

Stomach cancer

Commonly gastric adenocarcinoma; lymphoma; carcinoid (rare).

Early aggressive local spread with node/liver metastases. Often presents with weight loss, early satiety, and in some cases acanthosis nigricans

1) Intestinal - associated with H pylori, dietary nitrosamines (smoked foods), tobacco smoking, achlorhydria, chronic gastritis.

Commonly on lesser curvature; looks like ulcer with raised margins

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

Virschow node = involvement of left supraclavicular node by metastasis from stomach

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

Sister Mary Joseph nodule = subcutaneous periumbilical metastasis

72

Gastric vs Duodenal Ulcers in Peptic ulcer disease

1) Gastric
Pain - can be greater with meals - weight loss

H pylori - 70%

Mechanism - decreased mucosal protection against gastric acid

Other causes - NSAIDs

Risk of carcinoma - increased

Other - Biopsy margins to rule out malignancy

2) Duodenal
Pain - decreases with meals - weight gain

H Pylori - 100% almost

Mechanism - Decreased mucosal protection or increased gastric acid secretion

Other causes - Zollinger-Ellison Syndrome

Risk of carcinoma - generally benign

Other - Hypertrophy of Brunner glands

73

Ulcer complications

1) Hemorrhage
Gastric, duodenal (posterior > anterior).

Ruptured gastric ulcer on the lesser curvature of stomach leads to bleeding from L gastric artery.

An ulcer on the posterior wall of duodenum leads to bleeding from gastroduodenal artery

2) Perforation
Duodenal (anterior > posterior)

May see free air under diaphragm with referred pain to the shoulder via phrenic nerve

74

Malabsorption syndromes - general

Can cause diarrhea, steatorrhea, weight loss, weakness, vitamin and mineral deficiencies

Celiac Disease
Disaccharidase deficiency
Pancreatic insufficiency
Tropical sprue
Whipple Disease

75

Celiac Disease

A malabsorption syndrome

Autoimmune-mediated intolerance of gliadin (gluten protein found in wheat) leads to malabsorption and steatorrhea

Associated with HLA-DQ2, HLA-DQ8

Also associated with Northern European decent, dermatitis, herpetiformis, lower bone density

Findings = anti-endomysial, anti-tissue transglutaminase, and anti-gliadin antibodies; blunting of villi; and lymphocytes in lamina propria. Moderately increased risk of malignancy (T cell Lymphoma)

Lower mucosal absorption primarily affects distal duodenum and/or proximal jejunum

Tx = gluten-free diet

76

Disaccharidase Deficiency

A malabsorption syndrome

Most common is lactase deficiency - milk intolerance. Normal-appearing villi. Osmotic diarrhea.

Since lactase is located at tips of intestinal villi, self-limited lactase deficiency can occur following injury (viral enteritis)

Lactose intolerance test: (+) for lactase deficiency if administration of lactose produces symptoms and serum glucose rises

77

Pancreatic insufficiency

A malabsorption syndrome

Due to cystic fibrosis, obstructing cancer, chronic pancreatitis.

Causes malabsorption of fat and fat-soluble vitamins (ADEK) as well as B12

Increased neutral fat in stool

D-xylose absorption test - normal urinary excretion in pancreatic insufficiency; lower excretion with intestinal mucosal defects or bacterial overgrowth

78

Tropical sprue

A malabsorption syndrome

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

79

Whipple Disease

A malabsorption syndrome

Infection with Tropheryma whipplei (gram positive)

PAS (+) foamy macrophages in intestinal lamina propria, mesenteric nodes.

Cardiac symptoms, Arthralgias, and Neurologic symptoms are common. Most often occurs in older men

80

Crohn Disease

1) location - Any portion of GI tract, usually the terminal ileum and colon. Skip lesions, rectal sparing.

2) Gross morphology - Transmural inflammation - fistulas. Cobblestone mucosa, creeping fat, bowel wall thickening ("string sign" on Ba swallow XR), linear ulcers, fissures

3) Microscopic morphology - Noncaseating granulomas and lymphoid aggregates (Th1 mediated)

4) Complications - Strictures (leading to obstruction), fistulas (including enterovesical fistulae, which can cause recurrent polymicrobial UTIs), perianal disease, malabsorption, nutritional depletion, colorectal cancer, gallstone

5) Intestinal manifestation - Diarrhea that may or may not be bloody

6) Extraintestinal manifestations - Migratory polyarthritis, erythema nodosum, ankylosing spondylitis, pyoderma gangrenosum, aphthous ulcers, uveitis, kidney stones

7) Tx - Corticosteroids, azathioprine, antibiotics (ciprofloxacin, metronidazole), infliximab, adalimumab

81

Ulcerative Colitis

1) location - Colitis = colon inflammation. Continuous colonic lesions, always with rectal involvement

2) Gross morphology - Mucosal and submucosal inflammation only. Friable mucosal pseudopolyps with freely hanging mesentery. Loss of haustra - "lead pipe" on imaging

3) Microscopic morphology - Crypt abscesses and ulcers, bleeding, no granulomas (Th2 mediated)

4) Complications - Malnutrition, sclerosing cholangitis, toxic megacolon, colorectal carcinoma (worse with right sided colitis or pancolitis)

5) Intestinal manifestation - Bloody diarrhea

6) Extraintestinal manifestations - Pyoderma gangrenosum, erythema nodosum, primary sclerosing cholangitis, ankylosing spondylitis, aphthous ulcers, uveitis

7) Tx - 5-aminosalicylic preparations (mesalamine), 6-MP, infliximab, colectomy

UC causes ULCCCERS

Ulcers
Large Intestine
Continuous, Colorectal carcinoma, Crypt abscesses
Extends proximally
Red diarrhea
Sclerosing cholangitis

82

Irritable Bowel Syndrome

Recurrent abdominal pain associated with at least 2 of the following:

Pain improves with defecation
Change in stool frequency
Change in appearance of stool

No structural abnormalities. Most common in middle-aged women. Chronic symptoms. May present with diarrhea, constipation, or alternation symptoms. Pathophysiology is multifaceted. Treat the symptoms

83

Appendicitis

Acute inflammation of the appendix due to obstruction by fecalith (in adults) or lymphoid hyperplasia (in children)

Initial diffuse perumbilical pain migrates to McBurnery point (1/3 the distance from right anterior superior iliac spine to umbilicus).

Nausea, fever; may perforate - peritonitis; may elicit psoas, obturator, Rovsing sign, guarding and rebound tenderness on exam

Ddx = diverticulitis (elderly), ectopic pregnancy (use B-hCG to rule out)

Tx = appendectomy

84

Diverticulum

Blind pouch protruding from the alimentary tract that communicates with the lumen of the gut. Most diverticula (esophagus, stomach, duodenum, colon) are acquired and are termed "false" in that they lack or have an attenuated muscularis externa. Most often in sigmoid colon

"True" diverticulum - all 3 gut wall layers outpouch (Meckel)

"False" diverticulum or pseudodiverticulum - only mucosa and submucosa outpouch. Occur especially where vasa recta perforate muscularis externa

85

Diverticulosis

Many false diverticula of the colon, commonly sigmoid. Common (in 50% of people > 60)

Caused by increased intraluminal pressure and focal weakness in colonic wall. Associated with low-fiber diets.

Often asymptomatic or associated with vague discomfort. A common cause of hematochezia.

Complications include diverticulitis, fistulas

86

Diverticulitis

Inflammation of diverticula classically causing LLQ pain, fever, leukocytosis.

May perforate - peritonitis, abscess formation, or bowel stenosis. Give antibiotics

May also cause colovesical fistula (fistula with bladder) - pneumaturia

Sometimes called "left-sided appendicitis" due to overlapping clinical presentation

87

Zenker diverticulum

Pharyngoesophageal FALSE diverticulum

herniation of mucosal tissue at Killian triangle between the thyropharyngeal and cricopharyngeal parts of the inferior pharyngeal constrictor

Presenting symptoms = dysphagia, obstruction, foul breath from trapped food particles (halitosis)

Most common in elderly males

88

Meckel diverticulum

TRUE diverticulum. Persistence of the vitelline duct.

May contain ectopic acid-secreting gastric mucosa and/or pancreatic tissue.

*Most common congenital anomaly of GI tract.

Can cause melena, RLQ pain, intussusception, volvulus, or obstruction near terminal ileum.

Contrast with omphalomesenteric cyst = cystic dilation of vitelline duct

Dx = pertechnetate study for uptake by ectopic gastric mucosa

The five 2's

2 inches long
2 feet from ileocecal valve
2% of population
Commonly presents in first 2 years of life
May have 2 types of epithelia (gastric/pancreatic)

89

Malrotation

Anomaly of midgut rotation during fetal development leading to improper positioning of bowel, formation of fibrous bands (Ladd bands)

Can lead to volvulus, duodenal obstruction

90

Volvulus

Twisting of portion of bowel around its mesentery; can lead to obstruction and infarction. Can occur throughout the GI tract.

Midgut volvulus more common in infants and children. Sigmoid volvulus more common in elderly

91

Intussusception

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

Compromised blood supply leads to intermittent abdominal pain often with "currant jelly" stools. Unusual in adults (associated with intraluminal mass or tumor that acts as lead point that is pulled into the lumen)

Majority of cases occur in children (usually idiopathic; may be associated with recent enteric or respiratory viral infection)

Abdominal emergency in early childhood, with bull's eye appearance on ultrasound

92

Hirschsprung Disease

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

presents with bilious emesis, abdominal distention, and failure to pass meconium leading to chronic constipation

Normal portion of the colon proximal to the aganglionic segment is dilated, resulting in a "transition zone." Involves rectum.

Think of Hirschsprung as a giant spring that has sprung in the colon. Risk higher with Down Syndrome

Diagnosed by rectal suction biopsy

Tx = resection

93

Acute mesenteric ischemic

Critical blockage of intestinal blood flow (often embolic occlusion of SMA) leading to small bowel necrosis causing abdominal pain out of proportion to physical findings

May see red "currant jelly" stools

94

Adhesion

Fibrous band of scar tissue; commonly forms after surgery; most common cause of small bowel obstruction.

Can have well-demarcated necrotic zones

95

Angiodysplasia

Tortuous dilation of vessels leads to hematochezia

Most often found in cecum, terminal ileum, ascending colon. More common in older patients. Confirmed by angiography

96

Duodenal atresia

Causes early bilious vomiting with proximal stomach distention ("double bubble" on XR) bc of failure of small bowel recanalization. Associated with Down Syndrome

97

Ileus

Intestinal hypomotility without obstruction leading to constipation and decreased flatus; distended/tympanic abdomen with reduced bowel sounds.

Associated with abdominal surgeries, opiates, hypokalemia, sepsis

Tx = bowel rest, electrolyte correction, cholinergic drugs (stimulate intestinal motility)

98

Ischemic colitis

Reduction in intestinal blood flow causes ischemia. Pain after eating leading weight loss.

Commonly occurs at watershed areas (splenic flexure, distal colon)

Typically affects elderly

99

Meconium ileus

In cystic fibrosis, meconium plug obstructs intestine, preventing stool passage at birth

100

Necrotizing enterocolitis

Seen in premature, formula-fed infants with immature immune system

Necrosis of intestinal mucosa (primarily colonic) with possible perforation, which can lead to pneumatosis intestinalis, free air in abdomen, portal venous gas

101

Colonic polyps

Small 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

102

Hyperplastic polyps

Non-neoplastic

Generally smaller and majority located in rectosigmoid area

103

Hamartomatous polyps

Non-neoplastic

Solitary lesions do not have a significant risk of malignant transformation. Growths of normal colonic tissue with distorted architecture

Associated with Peutz-Jeghers syndrome and juvenile polyposis

104

Adenomatous polyps

Neoplastic

Via chromosomal instability pathway with mutations in APC and KRAS.

Tubular histology has less malignant potential than villous; tubulovillous has intermediate malignant potential

105

Serrated polyps

Premalignant

Via CpG hypermethylation phenotype pathway with microsatellite instability and mutations in BRAF

"saw-tooth" pattern of crypts on biopsy

Up to 20% of cases of sporadic CRC

106

Familial adenomatous polyposis (FAP)

Autosomal Dom mutation in APC tumor suppressor gene on chromosome 5q.

2 hit hypothesis

100% progresses to CRC unless colon is resected. Thousands of polyps arise starting after puberty; pancolonic; always involves rectum

107

Gardner Syndrome

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

108

Turcot Syndrome

FAP + malignant CNS tumor. "Turcot = Turban"

109

Peutz-Jeghers Syndrome

Autosomal Dom syndrome featuring numerous hamartomas throughout GI tract, along with hyperpigmented mouth, lips, hands. genitalia

Associated with higher risk of CRC

110

Juvenile Polyposis Syndrome

Autosomal Dom syndrome in children (typically younger than 5) featuring numerous hamartomatous polyps in the colon, stomach, small bowel.

Associated with higher risk of CRC

111

Lynch Syndrome

Previously known as "hereditary nonpolyposis colorectal cancer (HNPCC)"

Autosomal Dom mutation of DNA mismatch repair genes with subsequent microsatellite instability

80% progresses to CRC

Proximal colon is always involved

Associated with endometrial, ovarian, and skin cancers

Can be identified clinically in families using 3-2-1 rule

3 relatives with Lynch Syndrome-associated cancers across 2 generations, 1 of whom must be diagnosed before age 50 years old.

112

Colorectal cancer

Most patients are over 50. 25% have a family history

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

Rectosignmoid > ascending > descending

Ascending - exophytic mass, iron deficiency anemia, weight loss

Descending - infiltrating mass, partial obstruction, colicky pain, hematochezia

Rarely, presents with Strep Bovis bacteremia

Dx = iron deficiency anemia in males (especially over 50 years old) and postmenopausal female raises suspicion

Screen patients > 50 years old with colonoscopy, flexible sigmoidoscopy, or stool occult blood test

Apple core lesion seen on Ba enema XR

CEA tumor marker good for monitoring recurrence, not useful for screening

113

Molecular pathogenesis of colorectal cancer

There are 2 molecular pathways that lead to CRC

1) Microsatellite instability pathway (15%): DNA mismatch repair gene mutation leads to sporadic and Lynch Syndrome. Mutations accumulate, but no defined morphologic correlates

2) APC/B-catenin (chromosomal instability) pathway (85%) leads to sporadic cancer

Loss of APC gene puts normal colon at risk. (decreased intercellular adhesion and increased proliferation)

KRAS mutation puts the at risk colon into and adenoma (unregulated intracellular signal transduction).

Loss of tumor suppressor gene (p53, DCC) turns the adenoma into carcinoma (increased tumorigenesis)

"order of events = AK 53"

114

Cirrhosis and portal HTN

Cirrhosis - diffuse bridging fibrosis and nodular regeneration via satellite cells disrupts normal architecture of liver; increased risk of hepatocellular carcinoma (HCC)

Etiologies: alcohol (60-70% of cases in the US), chronic viral hepatitis, biliary disease, genetic/metabolic disorders

Portosystemic shunts partially alleviate portal HTN - esophageal varices, caput medusae, anorectal varices

115

Serum markers of liver and pancreas pathology

1) Alkaline phosphatase (ALP) - cholestatic and obstructive hepatobiliary disease, HCC, infiltrative disorders, bone disease

2) Aminotransferases (AST and ALT) (often called "Liver enzymes") - Viral hepatitis (ALT > AST), Alcoholic hepatitis (AST > ALT)

3) Amylase - Acute pancreatitis, mumps

4) Ceruloplasmin - Reduced in Wilson Disease

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

6) Lipase - Acute pancreatitis (most specific)

116

Reye Syndrome

Rare, often fatal childhood hepatic encephalopathy.

Findings: mitochondrial abnormalities, fatty liver (microvascular fatty change), hypoglycemia, vomiting, hepatomegaly, coma.

Associated with viral infection (esp VZV and influenza B) that has been treated with aspirin.

Mech: Aspirin metabolites lower B-oxidation by reversible inhibition of mitochondrial enzymes. Avoid aspirin in children, except in those with Kawasaki Disease*

117

Alcoholic liver disease

1) Hepatic steatosis - Macrovascular fatty change that may be reversible with alcohol cessation

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

Make a toAST with alcohol - AST > ALT (ratio usually > 1.5)

3) Alcoholic cirrhosis - Final and irreversible form. Micronodular, irregularly shrunken liver with "hobnail" appearance. Sclerosis around central vein (zone 3)

Manifestations of chronic liver disease (jaundice, hypoalbuminemia)

118

Non-alcoholic fatty liver disease

Metabolic syndrome (insulin resistance) leads to fatty infiltration of hepatocytes causing cellular "ballooning" and eventual necrosis. May cause cirrhosis and HCC. Independent of alcohol use

ALT > AST

119

Hepatic encephalopathy

Cirrhosis leads to portosystemic shunts leading to reduced NH3 metabolism causing neuropsychiatric dysfunction

Spectrum from disorientation/asterixis (mild) to difficult arousal or coma (severe).

Triggers:
Increased NH3 production and absorption (due to dietary protein, GI bleed, constipation, infection)

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

Tx = lactulose (increases NH4 generation) and rifaximin

120

Hepatocellular Carcinoma/Hepatoma

Most common primary malignant tumor of liver in adults. Associated with HBV (+/- cirrhosis) and all other causes of cirrhosis (including HCV, alcoholic and non-alcoholic fatty liver disease, autoimmune disease, hemochromatosis, alpha1 antitrypsin deficiency, Wilson Diseaes) and specific carcinogens (aflatoxin from Aspergillus)

May lead to Budd-Chiari Syndrome

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

Dx = increased alpha-fetoprotein; ultrasound or contrast CT/MRI, biopsy

121

Cavernous hemangioma

Liver tumor

Common, benign liver tumor; typically occurs at age 30-50 years. Biopsy contraindicated bc of risk of hemorrhage

122

hepatic adenoma

Liver tumor

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

123

Angiosarcoma

Liver tumor

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

124

Metastases

Liver tumor

GI malignancies, breast, and lung cancer. Most common overall**

125

Budd-Chiari Syndrome

Thrombosis or compression of hepatic veins with centrilobular congestion and necrosis leads to congestive liver disease (hepatomegaly, varices, abdominal pain, eventual liver failure)

Absence of JVD

Associated with hypercoagulable states, polycythemia vera, postpartum state, HCC

May cause nutmeg liver (mottled appearance)

126

Alpha1-antitrypsin deficiency

Misfolded gene product protein aggregates in hepatocellular ER leading to cirrhosis with PAS (+) globules in liver.

Codominant trait

In lungs, lower alpha1 antitrypsin leads to uninhibited elastase in alveoli leading to less elastic tissue causing panacinar emphysema

127

Jaundice

Abnormal yellowing of the skin and/or sclera due to bilirubin deposition. Occurs at high bilirubin levels ( > 2.5 mg/dL) in blood secondary to increased production or defective metabolism

128

Unconjugated (indirect) hyperbilirubinemia

Hemolytic, physiologic (newborn), Crigler-Najjar, Gilbert Syndrome

129

Conjugated (direct) hyperbilirubinemia

Biliary tract obstruction: gallstones, cholangiocarcinoma, pancreatic or liver cancer, liver fluke.

Biliary tract disease:
Primary sclerosing cholangitis
Primary biliary cirrhosis

Excretion defect: Dubin-Johnson syndrome, Rotor syndrome

130

Mixed (direct and indirect) hyperbilirubinemia

Hepatitis, Cirrhosis

131

Physiologic neonatal jaundice

At birth, immature UDP-glucuronosyltransferase leads to unconjugated hyperbilirubinemia causing jaundice/kernicterus (bilirubin deposition in brain, particularly basal ganglia)

Tx = phototherapy (converts unconjugated bilirubin to water-soluble form)

132

Gilbert Syndrome

Hereditary hyperbilirubinemia

Mildly reduced UDP-glucuronosyltransferase conjugation and impaired bilirubin uptake. Asymptomatic or mild jaundice.

Increased unconjugated bilirubin without overt hemolysis. Bilirubin increases with fasting and stress

Very common. No clinical consequences

133

Crigler-Najjar Syndrome, type 1

Hereditary hyperbilirubinemia

Absent UDP-glucuronosyltransferase. Presents early in life; patients die within a few years

Findings: jaundice, kernicterus (bilirubin deposition in brain), increased unconjugated bilirubin

Tx = plasmapheresis and phototherapy

Type 2 is less severe and responds to phenobarbital, which increases liver enzyme synthesis

134

Dubin-Johnson Syndrome

Hereditary hyperbilirubinemia

Conjugated hyperbilirubinemia due to defective liver excretion. Grossly black liver. Benign

Rotor Syndrome** is similar but even milder and does not cause black liver

135

Wilson Disease (hepatolenticular degeneration)

Inadequate hepatic copper excretion and failure of copper to enter circulation as ceruloplasmin. Leads to copper accumulatio, especially in liver, brain, cornea, kidneys (Fanconi syndrome), and joints

Autosomal recessive inheritance (chromosome 13). Copper is normally excreted into bile by hepatocyte copper transporting ATPase (ATP7B gene)

Treatment includes chelation with penicillamine or trientine, oral zinc

Characterized by:
Low Ceruloplasmin, Cirrhosis, Corneal deposits (Kayser-Fleischer rings). Copper accumulation, Carcinoma (HCC)

Hemolytic anemia

Basal ganglia degeneration (parkinsonian symptoms)

Asterixis

Dementia, Dyskinesia, Dysarthria

Copper is Hella BAD

136

Hemochromatosis

Hemosiderosis is the deposition of hemosiderin (iron), which stains blue; hemochromatosis is the disease caused by this iron deposition

Classic triad of micronodular Cirrhosis, Diabetes Mellitus and Skin pigmentation - "Bronze Diabetes"

results in HF, testicular atrophy, increased risk of HCC

Disease may be primary (auto recess) or secondary to chronic transfusion therapy (B-thalassemia major)

Increased ferritin
Increased Fe
Low TIBC
All this = high transferrin saturation

Can be identified on biopsy with Prussian blue stain

total body iron may reach 50g, enough to set off metal detectors at airports

Primary hemochromatosis due to C282Y or H63D mutation on HFE gene. Associated with HLA-A3

Iron loss through menstruation slows progression in women

Treatment of hereditary hemochromatosis: repeated phlebotomy, chelation with defarasirox, deferoxamine, deferiprone (oral)

137

Biliary tract disease - general

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

138

Secondary biliary cirrhosis

Extrahepatic biliary obstruction leads to increased pressure in intrahepatic ducts leading to injury/fibrosis and bile stasis

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

May be complicated by ascending cholangitis

139

Primary biliary cirrhosis

Autoimmune reaction leading to lymphocytic infiltrate + granulomas causing destruction of intralobular bile ducts

Classically in middle-aged women

Anti-mitochondrial antibody (+), including IgM

Associated with other autoimmune conditions (CREST, Sjogren syndrome, RA, Celiac)

140

Primary sclerosing cholangitis

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

Classically in young men with IBD

Hypergammaglobulinemia (IgM). MPO-ANCA/p-ANCA (+)

Associated with UC. Can lead to secondary biliary cirrhosis, cholangiocarcinoma

141

Gallstones (cholelithiasis)

Increased cholesterol and/or bilirubin, lower bile salts, and gallbladder stasis all cause stones

2 types of stones
1) Cholesterol stones (radiolucent with 10-20% opaque due to calcifications) - 80% of stones.

Associated with obesity, Crohn, advanced age, clofibrate, estrogen therapy, multiparity, rapid weight loss, Native American origin

2) Pigment stones (black = radiopaque, Ca bilirubinate, hemolysis; brown = radiolucent, infection) - seen in patients with chronic hemolysis, alcoholic cirrhosis, advanced age, biliary infections, total parenteral nutrition (TPN)

Stones most often cause cholecystitis; also ascending cholangitis, acute pancreatitis, bile stasis

Can also lead to biliary colic - neurohormonal activation (by CCK after a fatty meal) triggers contraction of gallbladder, forcing a stone into the cystic duct. May present without pain (in diabetes)

Can cause fistula between gallbladder and small intestine, leading to air in biliary tree and allowing the passage of gallstones into the intestinal tract. Gallstone may obstruct ileocecal valve leading to gallstone ileus

Diagnose with ultrasound. Treat with cholecystectomy if symptomatic

Risk factors = 4 F's
Female
Fat
Fertile (pregnant)
Forty

Charcot triad of cholangitis:
Jaundice
Fever
RUQ pain

142

Cholecystitis

Acute or chronic inflammation of gallbladder. Usually from cholelithiasis (gallstones); most commonly blocking the cystic duct leading to secondary infection; rarely ischemia or primary infection (CMV)

Murphy sign (+) - inspiratory arrest on RUQ palpation due to pain. Increased ALP if bile duct becomes involved (ascending cholangitis)

Diagnose with ultrasound or cholescintigraphy (HIDA, or hepatobiliary iminodiacetic acid scan)

143

Porcelain gallbladder

Calcified gallbladder due to chronic cholecystitis; usually found incidentally on imaging

Tx = prophylactic cholecystectomy due to high rates of gallbladder carcinoma

144

Acute pancreatitis

Autodigestion of pancreas by pancreatic enzymes

Causes: idiopathic, Gallstones, Ethanol, Trauma, Steroids, Mumps, Autoimmune disease, Scorpion sting, Hypercalcemia/Hypertriglyceridemia ( > 1000), ERCP, Drugs (sulfa drugs, NRTIs, protease inhibitors) - GET SMASHED

Clinical presentation - epigastric abdominal pain radiating to back, anorexia, nausea

Labs - high amylase and lipase (higher specificity)

Can lead to DIC, ARDS, diffuse fat necrosis, hypocalcemia (ca collects in pancreatic Ca soap deposits), pseudocyst formation, hemorrhage, infection, multiorgan failure

Complications - pancreatic pseudocyst (lined by granulation tissue, not epithelium; can rupture and hemorrhage)

145

Chronic pancreatitis

Chronic inflammation, atrophy, calcification of the pancreas. Major causes are alcohol abuse and idiopathic

Mutations in CFTR (cystic fibrosis) can cause chronic pancreatic insufficiency

Can lead to pancreatic insufficiency leading to steatorrhea, fat soluble vitamin deficiency, diabetes mellitus

Amylase and lipase may or may not be elevated (almost always elevated in acute pancreatitis)

146

Pancreatic adenocarcinoma

Average survival - 1 year after diagnosis. Very aggressive tumor arising from pancreatic ducts (disorganized glandular structure with cellular infiltration); already metastasized at presentation; tumors more common in pancreatic head (leading to obstructive jaundice). Associated with CA 19-9 tumor marker (also CEA, less specific)

Risk factors:
Tobacco use
Chronic pancreatitis (especially more than 20 years)
Diabetes
Age > 50
Jewish and black males

Often presents with:
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)

Tx = Whipple procedure, chemotherapy, radiation therapy