Small and large intestine pathology
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Small and large intestine pathology Presentation Transcript

  • 1.
    • SMALL AND LARGE INTESTINES
    • Congenital anomalies
    • a) Meckel diverticulum
    • i) blind pouch located on antimesenteric side of small bowel
    • - within 2 feet on ileocecal valve
    • ii) true diverticulum
    • - contains all 3 layers
    • iii) usually asymptomatic
    www.freelivedoctor.com
  • 2. www.freelivedoctor.com
  • 3.
    • Hirschsprung disease (aganglionic
    • megacolon)
    • a) lack of neural connection
    • i) devoid of Meisnner and Auerbach myenteric plexus
    • b) functional obstruction
    • i) dilation proximal to affected segment
    • ii) normal ganglia in dilated segment
    • iii) loss of ganglia in contracted segment
    www.freelivedoctor.com
  • 4. www.freelivedoctor.com
  • 5. iv) rectum always affected v) “short disease” involves rectum and sigmoid vi) “long disease” involves rectum and entire colon vii) male 4:1 - 10% with Down’s syndrome viii) enterocolitis, perforations with peritonitis are major causes of death www.freelivedoctor.com
  • 6.
    • c) acquired Hirschsprung
    • i) Chagas disease
    • ii) organic obstruction
    • - neoplasm
    • - inflammatory stricture
    • - toxic (UC or Crohn’s)
    • ENTEROCOLITIS
    • Diarrheal diseases
    • a) infections
    • b) malabsorption
    • c) inflammatory bowel disease
    www.freelivedoctor.com
  • 7.
    • Diarrhea and dysentery
    • a) diarrhea  > 250 grams stool/day
    • i) 70-95% water
    • b) dysentery  low volume, painful, bloody diarrhea
    • c) causes: see table 17-6
    • i) 5 categories
    • - secretory : > 500 ml fluid stool, isotonic, with fasting
    • - osmotic : > 500 ml fluid stool, stops with fasting, Osm > plasma (50 mOsm)
    www.freelivedoctor.com
  • 8.
    • - exudative : bacterial damage, bloody, persist with fasting
    • - motility disease : increased
    • - malabsorption : bulky stool,
    •  Osm, steatorrhea, stops with fasting
    • Infectious enterocolitis
    • a) > 12,000 deaths/day in children
    • in developing countries
    • b) 50% of all deaths worldwide
    • i) children < 5 yrs.
    www.freelivedoctor.com
  • 9. ii) self-limited diarrhea mostly caused by viruses c) viral gastroenteritis i) see table 17-7 ii) rotavirus - children 6-24 months - young children & debilitated adults - selectively destroys enterocytes in small intestine  malabsorption, secretory and Osm diarrhea www.freelivedoctor.com
  • 10. - peds. in hospitals and day- care centers - Ab in moms milk  infections seen at time of weaning iii) adenovirus - Ad31, Ad40 & Ad41 most common diarrhea in children - malabsorption and secretory diarrhea www.freelivedoctor.com
  • 11. iv) calicivirus - Sapporo-like (rare) - Norwalk-like (common); majority of nonbacterial food-borne epidemic gastroenteritis in all age groups v) astrovirus - 1 o children d) necrotizing enterocolitis i) neonates, premature, low birth weight (sm intest) www.freelivedoctor.com
  • 12. Necrotizing enterocolitis (NEC). Left picture shows an abdominal X-ray of a preterm infant with NEC. The presence of gas in the wall of the intestines (“pneumatosis intestinalis”) proves the diagnosis. Right picture on the top shows multifocal necrosis of the bowel, marked by the segmental dusky, hemorrhagic appearance. The most common sites of involvement are the terminal ileum and proximal colon. Right picture on the bottom shows a distended, congested, necrotic bowel (Compare the involved segment of intestine below with the more normal segment above.) www.freelivedoctor.com
  • 13.
    • MALABSORPTION SYNDROMES
    • defective absorption:
    • a) fats (hallmark)
    • b) CHO
    • c) protein
    • d) H 2 O
    • e) minerals
    • f) vitamins
    • chronic diarrhea and steatorrhea
    • see table 17-9
    • most common in USA:
    • a) celiac disease,Crohn's & Pancreatic
    www.freelivedoctor.com
  • 14. Celiac disease (“celiac sprue”, “gluten sensitive enteropathy”) a) chronic disease i) T-cell inflammatory reaction with autoimmune component b) mucosal lesions i) small intestine (duod-jejunum) c) improves with removal of gluten and related grain proteins from diet (i.e., wheat, oats, barley, rye) i)  CD8+ in mucosa when gluten present (IL-15 sensitive) www.freelivedoctor.com
  • 15. d) Caucasians e) familial i) class II HLA-DQ2 or HLA- DQ8 f) clinical: i) characteristic skin blisters - dermatitis herpetiformis ii) neurologic disorders iii) Dx: - history of malabsorption - lesion present via biopsy - improve without gluten www.freelivedoctor.com
  • 16. www.freelivedoctor.com
  • 17. www.freelivedoctor.com
  • 18. g) long term risk: i) NHL ii) adenocarcinoma iii) esophageal carcinoma Tropical sprue a) same characteristics as celiac b) Caribbean (not Jamaica), India, Africa, Asia c) NO specific causal agent found i) bacterial overgrowth ? - E. coli; Hemophilus www.freelivedoctor.com
  • 19. d) injury seen at all levels of small intestine e) usually folate/B 12 deficiency f) broad spectrum antibiotics i) bacterial origin ? g) no carcinoma susceptibility Whipple disease a) rare i) bacterium  - Tropheryma whippelii b) systemic condition www.freelivedoctor.com
  • 20. Fluorescent in situ hybridisation of a small intestinal biopsy in a case of Whipple's disease (confocal laser scanning microscopy). Tropheryma whipplei rRNA is blue, nuclei of human cells are green and the intracellular cytoskeletal protein vimentin is red. Magnification approximately 200 x. www.freelivedoctor.com
  • 21. i) affect any body part ii) mainly intestines, CNS and joints (1 o presentation) iii) small intestines: - distended macrophages - mucosal edema - lymphatic distension:  lipid deposition in villi  “ lipid dystrophy” iv) Caucasians; 10:1 male v) Dx = PAS+ macrophages - with rod shaped organisms www.freelivedoctor.com
  • 22. PAS Bacilli within macrophage Arthritis (often) Steatorrhea Encephalopathy (occasionally) Malabsorption And diarrhea lymphadenopathy Lipid pools in mucosa www.freelivedoctor.com
  • 23.
    • Disaccharidase (lactase) deficiency
    • a) rare (congenital form)
    • b) acquired is common
    • c) lactose  glucose + galactose
    • i) osmotic diarrhea
    • IDIOPATHIC INFLAMMATORY BOWEL DISEASE (IBD)
    • Chronic relapsing diseases
    • Crohn disease & Ulcerative colitis
    • activation of mucosal immune system
    www.freelivedoctor.com
  • 24.
    • Dx of IBD:
    • a) clinical history
    • b) lab and path findings
    • c) NO single test to Dx IBD nor to differentiate CD from UC
    • d) p-ANCA + is 75% with UC and only 11% with CD
    www.freelivedoctor.com
  • 25.
    • Crohn Disease
    • any level of alimentary tract
    • a) small intestine alone  40%
    • b) sm. Intestine + colon  30%
    • c) colon alone  30%
    • “ skip” lesions
    • pathological characteristics:
    • a) mucosal damage (transmural)
    • b) well demarcated regions
    • c) noncaseating granulomas
    • d) formation of fissures
    • e) narrowed lumen (obstruction)
    www.freelivedoctor.com
  • 26.
    • clinical:
    • a) more subtle than UC
    • b) diarrhea, fever, abdominal pain
    • i) lower right pain
    • - mimic appendicitis or
    • - perforation
    • c) colonic involvement  blood
    • i) anemia over time
    • d) bimodal age distribution
    • i) 10-30 and 50-70 yrs
    • e) Caucasians 5:1 vs. noncaucasians
    www.freelivedoctor.com
  • 27. f) chronic course may lead to: i) fibrosing strictures - terminal ileum - fistulas other areas ii) protein loss iii) Vit B 12 loss iv) bile salt loss - steatorrhea v) linear serpentine ulcers www.freelivedoctor.com
  • 28. e) extraintestinal: (altered immunity) i) polyarthritis ii) erythema nodosum iii) clubbing of fingers iv) ankylosing spondylitis v)  risk of GI carcinoma - less than UC www.freelivedoctor.com
  • 29. www.freelivedoctor.com
  • 30.
    • Ulcerative colitis
    • inflammatory disease limited to colon
    • affecting mucosa and submucosa
    • a) except in most severe cases
    • i) transmural
    • extends in continuous fashion
    • a) from rectum
    • well formed granulomas are absent
    • as with CD, UC is systemic disease
    •  incidence vs. CD
    • age peak 20-30 yrs
    www.freelivedoctor.com
  • 31.
    • involves rectum and extends
    • retrograde to involve entire colon
    • a) “pancolitis”
    • b) disease of continuity
    • i) NO skip lesions
    • c) more common than CD
    • d) NO mural thickening vs. CD
    • e) with severe cases  toxic megacolon
    • i) muscularis and neural plexus
    • involvement
    • - neuromuscular failure
    www.freelivedoctor.com
  • 32.
    • f) ulceration of distal colon or
    • throughout its length
    • g) evolution of UC  dysplasia  carcinoma
    • clinical:
    • a) relapsing bloody mucoid diarrhea
    • i) relieved by defecation
    • - 1 st initial signs
    • b) long term complication  CA
    • i)  with pancolitis (25X normal)
    • c) see table 17-10
    • i) Crohn vs. UC
    www.freelivedoctor.com
  • 33. Patients with ulcerative colitis can occasionally have aphthous ulcers involving the tongue , lips , palate and pharynx   Endoscopic image of ulcerative colitis showing loss of vascular pattern of the sigmoid colon , granularity and some friability of the mucosa . www.freelivedoctor.com
  • 34.
    • VASCULAR DISORDERS
    • Ischemic bowel disease
    • a) small and/or large intestine
    • i) depending on vessel(s)
    • - superior mesenteric
    • - celiac
    • - inferior mesenteric
    • Types:
    • a) transmural infarcts
    • i) mechanical compromise
    • - major mesenteric vessels
    www.freelivedoctor.com
  • 35.
    • b) mucosal (i.e., mural) infarcts
    • i) hypoperfusion
    • c) venous compromise is a less frequent cause of infarcts
    • Causes:
    • a) arterial thrombosis
    • i) atheroma (origin of vessel), angiography (i.e., Ca ++ ), BC pills b) arterial embolism
    • i) atheroemboli (i.e., plaques), cardiac vegetations
    www.freelivedoctor.com
  • 36. c) nonocclusive ischemia i) cardiac failure ii) shock iii) vasoconstrictive drugs d) venous thrombosis i) BC pills ii) hypercoagulable states iii) peritonitis iv) invasive neoplasms v) cirrhosis vi) abdominal trauma e) other (radiation, herniation, etc.) www.freelivedoctor.com
  • 37. www.freelivedoctor.com
  • 38.
    • clinical:
    • a) embolic injury mainly affects
    • i) SMA
    • b) injury
    • i) initial hypoxic insult
    • ii) reperfusion injury
    • - most of intestinal injury
    • c) bowel infarction is uncommon
    • i) 50-75% lethality
    • ii) older population (disease)
    • d) abdominal pain
    • e) bloody diarrhea
    www.freelivedoctor.com
  • 39.
    • f) vasculitides:
    • i) PAN
    • ii) WG
    • iii) Henoch-Schönlein disease
    • Hemorrhoids
    • a) vertical dilations of anal and perianal venous plexuses
    • i) causes:
    • - straining with constipation
    • - venous stasis of pregnancy
    www.freelivedoctor.com
  • 40. www.freelivedoctor.com
  • 41.
    • DIVERTICULAR DISEASE
    • Blind pouch
    • a) congenital
    • i) involve all 3 layers
    • - Meckel diverticulum
    • b) acquired
    • i) lack or attenuated muscularis
    • ii) most common location
    • - left side of colon
    • - majority in sigmoid
    www.freelivedoctor.com
  • 42. www.freelivedoctor.com
  • 43.
    • iii) rare < 30 yrs
    • iv) > 60 yrs common (~ 50%)
    • v) occur in multiples
    • - “diverticulosis”
    • pathogenesis:
    • a) focal weakness in colonic wall
    • b)  intraluminal pressure
    • i) lack of fiber in diet
    • ii) causes “sequestration”
    • clinical:
    • a) cramping; feeling “not able to empty”; blood loss
    www.freelivedoctor.com
  • 44. Colonic diverticula are acquired herniations in which the mucosa and submucosa protrude through weak spots in the muscular layer of the colon wall. They are usually multiple (can vary from a few to hundreds) and are referred to as diverticulosis. The sigmoid colon is the location of most cases of diverticulosis (95%) , although any part of the colon can be involved. They often appear on the serosal surface in parallel rows between the teniae as seen in the gross specimen across www.freelivedoctor.com
  • 45. Histologically, colonic diverticula have a thin wall composed of a flattened mucosa and submucosa, and a markedly attenuated and often totally absent muscularis propria layer. In most diverticula, the base of the structure consists only of a thin serosal connective tissue layer. The adjacent bowel wall surrounding diverticula shows prominent hypertrophy and thickening of the muscularis propria. www.freelivedoctor.com
  • 46.
    • INTESTINAL OBSTRUCTION
    • occur at any level
    • a) small intestine most often
    • i) narrow lumen
    • causes:
    • a) see table 17-11
    • i) hernias, volvulus, adhesions and intussusception > 80% of cases
    • b) hernias:
    • i) weakness or defect in wall of peritoneal cavity
    • - protrusion  hernial sac
    www.freelivedoctor.com
  • 47. ii) inguinal, umbilical and scar areas - most are small bowel www.freelivedoctor.com
  • 48.
    • NEOPLASMS
    • small intestine
    • a) uncommon here
    • b) benign :
    • i) adenomas and mesenchymal are most common benign
    • - near ampulla of Vater
    • - occult blood loss
    • - CA precursor
    • ii) others are lipomas, angiomas and harmartomas
    www.freelivedoctor.com
  • 49. c) malignant : i) adenocarcinoma, carcinoid, lymphomas and sarcomas ii) most in the duodenum iii) near ampulla of Vater may cause obstructive jaundice iv) obstruction major complaint - pain, cramping, nausea, vomiting, weight loss, tired (due to blood loss) v)  risk from IBD (e.g., CD) and celiac disease, etc. www.freelivedoctor.com
  • 50.
    • large intestine (colon and rectum)
    • a) colorectal CA very common malignancies in Western countries
    • b) benign :
    • i) polyps
    • - tumorous mass protruding into lumen
    • - sessile (without stalk) or
    • - pedunculated (stalk)
    www.freelivedoctor.com
  • 51. www.freelivedoctor.com
  • 52. Tubular adenoma of the colon. This lesion was removed with snare-electrocautery during colonoscopy. Note the stalk of normal tan mucosa and the multilobulated head of the polyp. The stalk is formed when the polyp grows to a size that allows it to be pulled on by peristaltic forces. www.freelivedoctor.com
  • 53. ii) nonneoplastic polyps - hyperplastic (~ 95%) NO malignant potential - harmartomous (juvenile) RISK of CA - harmatomous (Peutz-Jeghers) AD genetics. Multiple scattered throughout GI tract. Melanin color around lips, face, palms. NO risk of polyp  CA. Risk of intussusceptions. CA risk of breast, lungs, ovary and uterus. www.freelivedoctor.com
  • 54. www.freelivedoctor.com
  • 55. www.freelivedoctor.com
  • 56. Enterography: Lobulated polyps in the small bowel (arrows) cause intermitting obstruction (arrows). www.freelivedoctor.com
  • 57. www.freelivedoctor.com
  • 58. - inflammatory (“pseudo”) - lymphoid iii) adenomas - polyp types: 1.- tubular (most common) 2.- villous 3.- tubulovillous - arise from dysplasia, low grade to high grade (CA in situ) - precursor to invasive colorectal CA - slow growing (10 yrs. to 2x) www.freelivedoctor.com
  • 59.
    • clinical (adenomas):
    • a) asymptomatic
    • i) evaluation of anemia/bleed
    • b) evolution to malignancy:
    • i) high grade dysplasia
    • ii) penetration through muscularis into submucosa
    • - invasive CA
    • - polypectomy Tx if:1-CA not invasive of stalk; 2-no vascular invasion; 3-not poorly differentiated
    www.freelivedoctor.com
  • 60.
    • Familial syndromes (familial polyposis)
    • a) AD genetics
    • b)  risk of CA
    • i) FAP  ~100% risk
    • c) FAP (familial adenomatous polyposi)
    • i) caused by mutation on chromosome 5q21
    • - APC gene (adenomatous polyposi coli)
    www.freelivedoctor.com
  • 61. Familial polyposis The colon is covered in a carpet of adenomatous polyps. www.freelivedoctor.com
  • 62. ii) further classified: - 1) attenuated - 2) Gardner syndrome - 3) Turcot syndrome 1.- attenuated a) fewer polyps (avg. ~ 30) b) most in proximal colon c) lifetime risk of CA ~ 50% www.freelivedoctor.com
  • 63. 2. – Gardner syndrome a) # polyps same as classical FAP b) multiple osteomas i) skull, mandible and long bones c) epidermal cysts d) fibromatosis e)  risk of duodenal and thyroid CA www.freelivedoctor.com
  • 64. Dental panoramic tomogram shows a sharply defined, large radiopaque lesion consisting of several clumped toothlets on the right mandibular corpus. www.freelivedoctor.com
  • 65.
    • 3.- Turcot syndrome
    • a) rare
    • b) colonic polyposis
    • c) CNS tumors (medulloblastoma – APC mutations - ~67%; glioblastoma – other gene (HNPCC) mutations – 33%
    • HNPCC (hereditary nonpolyposi
    • colorectal cancer)
    • a) AD genetics; DNA repair gene
    • b)  risk of colorectal CA and endometrium
    www.freelivedoctor.com
  • 66.
    • COLORECTAL CARCINOMA
    • most occur sporadically
    • Well defined sequence
    • a) adenoma  carcinoma
    • i) populations with  incidence of adenoma have  risk of carcinoma
    • ii) distribution similar to adenomas
    • iii) some dysplastic lesions can evolve CA w/out polyp (adenoma) phase
    www.freelivedoctor.com
  • 67.
    • pathways:
    • a) APC/ β -caterin – (“first hit”)
    • i) chromosomal instability
    • - loss of APC gene
    • 5q21 (FAP)
    • b) 80% of colorectal CA patients have APC inactivation
    • c) 50% of CA without APC mutations have β -caterin mutations
    • d) APC function:
    • i) cell adhesions & regulates proliferation
    www.freelivedoctor.com
  • 68.
    • e) other genetic factors:
    • i) K-RAS mutations
    • ii) loss of SMAD (2 and 4)
    • -  tumorogenesis
    • f) loss of p53
    • g) activation of telomerase
    • CA
    • a) 98% in colon are adenocarcinomas
    • i) usually arise in polyps
    • b) peak age 60-80 yrs.
    • i) if occurs < 50 yrs – other factors (UC, FAP, etc.)
    www.freelivedoctor.com
  • 69. c) environmental factors i) diet !! - immigrants from low risk CA countries coming to USA develop increased risk of CA - implicated are: 1.  fiber intake 2.  caloric intake vs. requirement 3.  unrefined CHO 4. red meat www.freelivedoctor.com
  • 70.
    • clinical:
    • a) in proximal colon
    • i) polypoid lesion
    • - obstruction uncommon
    • - bleeding
    • b) in distal colon
    • i) encircling ring
    • - “napkin ring” constriction
    • - constipation & reduced caliber of stool
    • - dx earlier vs. proximal
    • c) asymptomatic for years
    www.freelivedoctor.com
  • 71. Figure 17-61 Carcinoma of the cecum. The fungating carcinoma projects into the lumen but has not caused obstruction. Figure 17-62 Carcinoma of the descending colon. This circumferential tumor has heaped-up edges and an ulcerated central portion. The arrows identify separate mucosal polyps. www.freelivedoctor.com
  • 72. d) iron deficiency anemia in older male means GI CA until disproved ! e) metastasize to regional lymph nodes, liver, bone etc. f) Most important prognostic indicator i) extent or STAGE of tumor at time of diagnosis - TNM classification see Table 17-14 www.freelivedoctor.com
  • 73. Figure 17-64 Pathologic staging of colorectal cancer. Staging is based on the depth of tumor invasion www.freelivedoctor.com
  • 74.
    • Carcinoid tumors
    • a) possess endocrine cells
    • i) lung also had endocrine cells
    • ii) most carcinoids are from gut
    • b) ~ 2% of colorectal CA
    • i) ~ 50% of small intestine CA
    • c) most common site is appendix, followed by small intestine (ileum)
    • i) appendix and rectal carcinoids rarely metastasize !
    • d) solid, yellow-tan appearance
    • e) rarely produce local symptoms
    www.freelivedoctor.com
  • 75. f) can release hormones directly into circulation i) Zollinger-Ellison syndrome -  gastrin from pancreatic carcinoid  many peptic ulcers g) “carcinoid” syndrome (see table 17-15) i)  serotonin (5-HT) and its metabolite (5-HIAA) hydroxyindoleacetic acid www.freelivedoctor.com
  • 76. www.freelivedoctor.com
  • 77. www.freelivedoctor.com
  • 78.
    • GI Lymphoma
    • a) secondary involvement by NHL
    • i) gut 1 o site
    • b) primary GI lymphoma show NO:
    • i) liver
    • ii) spleen
    • iii) bone marrow
    • iv) mediastinal lymph node
    • involvement !!
    • c) B- or T-cell lymphoma
    • i) B-cell  MALT or IPSID and Burkitt lymphoma (NHL)
    www.freelivedoctor.com
  • 79. ii) MALT most common in USA - adults - no gender preference - CD5 and CD10 negative - anywhere in gut - H. pylori may be driving force (e.g., gastric MALT lymphoma) iii) IPSID (“Mediterranean lymphoma”) - B-cell (plasmacytosis) - infection plays a role www.freelivedoctor.com
  • 80. iv) T-cell lymphoma - long term malabsorption syndrome (i.e., celiac disease) - 30-40 yrs. (10-20 yr symptoms) - proximal bowel - poor prognosis vs. B-cell www.freelivedoctor.com
  • 81.
    • PERITONEUM
    • Inflammation (peritonitis)
    • a) sterile
    • i) mild leakage of bile or pancreatic enzymes
    • b) acute hemorrhagic pancreatitis
    • i) fat necrosis
    • c) perforations of biliary system
    • d) surgical procedures
    • i) adhesions
    • ii) granulomas (talc)
    www.freelivedoctor.com
  • 82.
    • tumors
    • a) all are malignant (rare)
    • i) primary:
    • - mesothelioma
    • - desmoplastic small round cell tumor t(11,22)
    • b) secondary:
    • i) common
    • - ovarian
    • - pancreatic
    • - any intra-abdominal malignancy
    www.freelivedoctor.com