The Small Intestine (Plus Free Bonus Organ: The Pancreas)

November 4, 2011

Outline-Small Intestine• Reading: Robbins 8th, Pages 790-807

Normal/functional anatomy

• Congenital Anomalies/Obstruction

• Ischemic Bowel Disease

• Malabsorption Syndromes

• Infectious Enterocolitis

• Irritable Bowel Syndrome

• Neoplasms of the Small Intestine

Outline- Pancreas

• Robbins 8th: Chapter 19, page 891-903

• Normal Function• Acute & Chronic Pancreatitis• Cystic Pancreatic Disease• Benign and Malignant Neoplasms

• CASE DISCUSSIONS:• CASE 1: Celiac Disease• CASE 2: Infectious Diarrhea – HIV+ pt• CASE 3- Pancreatic Cancer

Normal SI Anatomy

• Mucosa (Epis, LP, MM)– Columnar absorptive cells– Goblet Cells– Paneth Cells– Enteroendocrine Cells– IEL’s– LP: lymphocytes, vessels,

lymphatics

• Submucosa• Muscularis• Serosa

SI: Functional Anatomy

• Columnar absorptive cells: nutrient absorption– Ileum: Receptor for Intrinsic factor/vitamin

B12 complexes

• IgA production/secretion

• Paneth cells: Antimicrobial peptides

• Goblet Cells:Mucous layer: 1o barrier

• Epithelium completely renewed q4-6d.

Congenital Anomalies- I Malrotation- 2o to improper embryologic rotation. Can

lead to volvulus or acute SBO in 1st month of life. • Omphalocele, (1:5000 births) failure of abdominal

musculature formation; herniation of abdominal contents into a ventral membranous sac

• Gastroschisis, in which a portion of the abdominal wall fails to form altogether, causing extrusion of the intestines.

• Atresia- Failure of canalization (duodenal)

• Heterotopias: nodules of pancreatic tissue in wall of stomach, SI, or colon

Congenital Anomalies- II

• Meckel’s Diverticulum• Usually the vitelline duct (gut to

yolk sac) closes completely• Failure of involution = Meckels’

diverticulum• Usually within 2 feet of the

ileocecal valve, up to 6 cm long• Present in 2% of the population

• So what? – While usually lined with SI

mucosa, up to 50% have heterotopic gastric glands. Acid causes ulcers, mimics appy, or (rarely) perfs.

Obstructive Diseases• Herniation- Peritoneal

wall defect- incarceration

• Adhesions-Post-surgical, peritonitis, endometriosis

• Intussusception – ‘Telescoping’ of bowel segment

• Volvulus- Twisting on mesentery and its vessels

Small Bowel Obstruction

• 75% is 2o to previous surgery- fibrous adhesions between loops of bowel

• Most of remainder = hernias, metastatic colon CA

• 15% of all laparotomy pts readmitted for SBO <2 yrs post-op, 3% get re-operated upon

• CLIN: Abd distention, N/V, pain, no flatus• DX: Upright plain film: air-fluid levels• RX: “Lysis of Adhesions”

Malabsorption Syndromes

• Defective nutrient absorption→diarrhea– Typically: increased fecal fat = steatorrhea

• Due to disturbed:– Intraluminal digestion (pancreatic insufficiency)– Terminal digestion (lactose intolerance)– Transepithelial transport (abetalipoproteinemia)

• All have systemic effects– Hematopoietic, skeletal, endocrine,skin, PNS

Celiac Disease

• AKA celiac sprue, GSE• DEF: chronically impaired SI absorption which

improves upon gliadin withdrawl• Most common in whites, 1:100 (!) in Europe.

97% pts have HLA-DQ2 or DQ8 haplotype• PF: Gliadin binds MHC-II, activates T-cells,

release IFN, which damages villi• Long term ↑ risk of NHL, 50-100x fold risk of SI

carcinoma, esophageal Squamous Ca.

Celiac Disease• CLIN: Variable onset, severity.

– Symptoms:• diarrhea, flatulence, wt. loss, fatigue• Dermatitis herpetiformis

– Lab:• Anti-endomysial IgA, anti-gliadin IgA• Characteristic small bowel bx, proximal >

distal:•

Whipple Disease• Caused by Tropheryma whippelii

• Systemic, prominent involvement of SI

• Bugs proliferate within M, fill and distend LP

• 10:1 M:F, middle aged men. Present with malabsorption, joint pain, lymphadenopathy

Disaccharidase (Lactase) Deficiency

• Infants: 50% of daily calories (5-10% in adults)• Most intolerance is acquired…. (2o to celiac disease (most

common) or s/p enteric infection)• Incidence varies with ethnicity

– 90% in native Americans – 70% in Africans &Asians – 10% Caucasians

• Incomplete digestion leads to colonic bug conversion to SCFA and H2.

• Sx: Osmotic diarrhea, ab pain, bloating• DX: Typical sx + lactose tolerance test OR breath H2 test• Rx: Diet modification, ensure adequate Ca2+ uptake in ♀

Small Intestinal Neoplasms

• SI comprises 75% of the gut, only 5% of neoplasms

• Benign:adenomas, GI stromal tumors

• Malignant: adenocarcinoma, carcinoid, lymphoma

• Most SI CA’s are duodenal. Risk factors =Crohn’s Dz, FAP, HNPCC,

Carcinoid Tumors

• The civilized end of the spectrum of neuroendocrine neoplasms

• Derived from resident enteroendocrine cells– 2% of colonic, 50% of small intestinal malignancies– Arise in all mucosal surfaces, most common in

appendix, terminal ileum, rectum

Carcinoid Tumors

– CLIN: Sx depend on site, may be ‘functional’• Zollinger-Ellison Syndrome – gastrin• Cushing syndrome- corticotropin• Hyperinsulinism

-Most are low-grade malignancies, >90% 5 yr survival

– Cannot tell behavior by histology alone! • Aggression DOES correlate with size, site

– Appendiceal/rectal carcinoids rarely metastasize– 90% of muscle invasive gastric/ileal/colonic tumors have

LN and liver mets by the time of diagnosis

Carcinoid Tumors- II

The Pancreas

• For your Surgery rotation:– “Eat when you can, sleep when you can, and

don’t ever **** with the pancreas.”

• For your Pathology course:– Chapter 19, pages 891-903

Congential Pancreatic Abnormalities

• Normally formed by fusion of dorsal and ventral anlage/primordia

• Pancreas Divisum: Seen in 5-10% of people– Failure of fusion of ventral and dorsal ducts– Most pancreatic output from narrow minor duct– Predisposes these folks to chronic pancreatitis

• Annular pancreas: Rare– Ring of pancreas around 2nd portion of duodenum

• Young adult pts present with sx of duodenal obstruction

Pancreatitis

• Great variations in duration, severity

• Acute: Short term, reversible if cause identified/treated

• Chronic: irreversible damage to exocrine tissue

Acute Pancreatitis

• 80% of U.S. cases 2o to alcoholism, gallstones

• Other causes:– Ductal obstruction (neoplasms, pancreas divisum)– Drugs (more than 85 reported)– Hyperlipidemia, vasculitis– 10% cases are idiopathic– Blunt trauma, or s/p surgery or ERCP

What is ERCP?

• Scope thru Stomach to 1st segment of Duodenum

• Cannulate CBD via major papilla (duct of Wirsung)

• Shoot contrast- lights up CBD, intrahepatic R&L bile ducts, branches by fluoroscopy

Pathogenesis (see Fig. 19-6)

• Autodigestion via inappropriately activated enzymes. 3 possibilities for this:

1. Ductal obstruction →stasis →lipase gets to work

2. Direct acinar cell injury (viruses, drugs, trauma)

3. Alterations in intracellular proenzyme transport (sent to lysosomes, get activated in situ)

Clinical Features of Acute Pancreatitis

• Acute Pancreatitis is a Medical Emergency– Present with ‘acute abdomen’:

• Intense abdominal pain, radiates to upper back• Cytokine release may be systemic (SIRS), cause

– ↑[WBC], hemolysis, DIC, ARDS, Vascular collapse, shock

– Lab findings:• Elevated Amylase first, then elevated serum lipase• Elevated serum glucose• Hypocalcemia 2o to fat necrosis

• Mortality is 5-10% in the first week

Morphology of Acute Pancreatitis

• Ranges from edema & mild inflamm to necrosis and hemorrhage

• Fat necrosis from leaked lipolytic enzymes induces acute inflammatory response

• In severe cases, necrosis involves vasculature, get hemorrhage into parenchyma

Chronic Pancreatitis

• Inflammation & destruction of exocrine, then endocrine pancreas

• Most commonly due to long-term alcoholism

• Also:– long-standing duct obstruction– People with ‘minor’ CFTR mutations– 40% idiopathic, though hereditary gene loci now

known

Morphology of Chronic Pancreatitis

• Fibrosis, loss of acini, preserved Islets

• Ductal obstruction/plugging

Cystic Pancreatic Disease• Most (75%) are non-neoplastic pseudocysts

– Collections of necrotic debris after acute pancreatitis (most common: after a 72 hr bender)

– Most resolve, but may become infected, or perf

• Congenital cysts: True cysts, are found as part of VHL, AD-PCKD)

Pancreatic Neoplasms• Cystic Neoplasms:

– 10% of pancreatic cysts are neoplastic

• Benign: Serous cystadenoma– Multiple small serous cysts, cuboidal lining

• 2:1 F:M, older pts. May be palpable.

Mucinous Cystic Neoplasms• Almost always in women, usually in tail

• Do NOT communicate with the main duct

• Variable behavior: Benign, → borderline, → malignant.

• Dx depends on cytologic features, presence or absence of invasion

Pancreatic Cancer• 4th Leading cause of U.S. cancer deaths

(behind lung, colon, and breast)

• 30K people/yr get it, 30K/yr die from it

• Natural History: Multigenic disease – Progression from normal → PanIN →malignancy

Epidemiology

• Causes are poorly understood – Smoking → 2x risk– Fatty diet? – Chronic pancreatitis? CA blocks duct, causes it.– DM? – 80% cases in pts over 60 years old

Clinical Features

• Pain is usually first symptom

• Obstructive jaundice

• Weight loss, anorexia,

• Trousseau’s sign: migratory thrombophlebitis– Tumor-derived procoagulants → venous

thromboses

• Clinical course:– Only 20% resectable

Morphology• 60% arise in head, 15% in body, 5% in tail• Most arise from ductal epithelium

– Highly invasive, even early on– Clinically silent until they invade something– If in head, 50% obstruct the distal CBD

• Most of these pts develop jaundice

– If in tail, asymptomatic until well advanced– Invade thru retroperitoneum, into nodes, liver– Peri-/Intraneural invasion: intractable pain

Gross/Micro features:• Stellate, hard mass → desmoplasia

– Due to stromal response to invading glands– Epithelial component usually poorly differentiated

Whipple procedure, AKA pancreaticoduodenectomy

Ampullary Carcinomas

• Arise in the area of the ampulla,

• Rare, incidence increased in FAP patients

• Most follow from ampullary adenomas

• Tend to obstruct & become symptomatic early, so better prognosis– 90% of cases resectable, 50% 5 yr survival

ONWARD TO LAB!!!!!!