the small intestine (plus free bonus organ: the pancreas) november 4, 2011
TRANSCRIPT
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!!!!!!