DISEASES OF THE SMALL & LARGE INTESTINES Developmental anomalies Developmental anomalies –Atresia, stenosis, Meckel ’ s diverticulum, malrotation –Hirschsprung ’ s disease Vascular disorders Vascular disorders Inflammatory & diarrheal diseases Inflammatory & diarrheal diseases –Enterocolitis, malabsorption syndromes Idiopathic inflammatory bowel diseases Idiopathic inflammatory bowel diseases –Crohn ’ s disease, ulcerative colitis Colonic diverticular diseases Colonic diverticular diseases Tumors Tumors

PATHOLOGY OF THE SMALL INTESTINE DEVELOPMENTAL ANOMALIES Atresia or stenosis: involving a segment of bowel Atresia or stenosis: involving a segment of bowel Duplication: well-formed saccular structure which may or may not communicate with bowel lumen Duplication: well-formed saccular structure which may or may not communicate with bowel lumen Meckel ’ s diverticulum:most common, benign anomaly Meckel ’ s diverticulum:most common, benign anomaly –Failure of involution of the omphalomesenteric duct –Blind-ended tubular protrusion, <6 cm in length –In ileum, within 2 feet of cecum –Heterotopic gastric mucosa in 1/2 of cases (c/o bleeding & pain); rarely heterotopic pancreatic rests Omphalocele: defect in periumbilical abdominal wall, resulting in a membranous sac; +/- intestinal herniation Omphalocele: defect in periumbilical abdominal wall, resulting in a membranous sac; +/- intestinal herniation

DEVELOPMENTAL ANOMALIES OF THE LARGE INTESTINE MALROTATION The developing cecum fails to descend to its definitive adult position in the right lower quadrant. The cecum may be found anywhere in the abdomen. The developing cecum fails to descend to its definitive adult position in the right lower quadrant. The cecum may be found anywhere in the abdomen. Clinical features: Clinical features: –May be asymptomatic –May cause clinical problems: volvulus Diagnosis of acute appendicitis may be a problem Diagnosis of acute appendicitis may be a problem

DEVELOPMENTAL ANOMALIES OF THE LARGE INTESTINE HIRSCHSPRUNG’S DISEASE aka: congenital megacolon aka: congenital megacolon Failure of development of Meissner ’ s & Auerbach ’ s plexuses due to arrest in migration of neural crest-derived cells along GIT Failure of development of Meissner ’ s & Auerbach ’ s plexuses due to arrest in migration of neural crest-derived cells along GIT Ganglion cells are lacking at anorectal junction & distal colon, causing functional obstruction and progressive distension (megacolon) of the innervated colon proximal to the affected segment Ganglion cells are lacking at anorectal junction & distal colon, causing functional obstruction and progressive distension (megacolon) of the innervated colon proximal to the affected segment In 20% of patients, a longer segment is aganglionic In 20% of patients, a longer segment is aganglionic Patients: 1 in live births; M:F=4:1 Patients: 1 in live births; M:F=4:1 Associated with other congenital anomalies: hydrocephalus, VSD, Meckel ’ s diverticulum Associated with other congenital anomalies: hydrocephalus, VSD, Meckel ’ s diverticulum

HIRSCHSPRUNG DISEASE

PATHOLOGY & CLINICAL FEATURES OF HIRSCHSPRUNG’S DISEASE Pathology: Lack of ganglion cells in muscularis & submucosa of affected (nondistended) distal segment; unaffected proximal segment will be dilated, with thin wall (occasionally thick) & possible stercoral ulcers Pathology: Lack of ganglion cells in muscularis & submucosa of affected (nondistended) distal segment; unaffected proximal segment will be dilated, with thin wall (occasionally thick) & possible stercoral ulcers Clinical symptoms: Delayed passage of meconium, vomiting in hrs and obstructive constipation Clinical symptoms: Delayed passage of meconium, vomiting in hrs and obstructive constipation Complications: enterocolitis, fluid & electrolytes disturbances Complications: enterocolitis, fluid & electrolytes disturbances Dx: full thickness biopsy of nondistended bowel segment Dx: full thickness biopsy of nondistended bowel segment Rx: surgical Rx: surgical

PATHOLOGY OF SMALL & LARGE INTESTINE DIARRHEAL DISORDERS Diarrhea= increase in stool mass, frequency or fluidity Diarrhea= increase in stool mass, frequency or fluidity Daily stool production>250 gm, containing 70-95% water Daily stool production>250 gm, containing 70-95% water Dysentery= low volume painful bloody diarrhea Dysentery= low volume painful bloody diarrhea Classification of diarrheal disorders: Classification of diarrheal disorders: –Secretory diarrhea: direct or enterotoxin-mediated damage to surface epithelium –Osmotic diarrhea: osmotic forces of luminal solutes –Exudative diarrhea: destruction of epithelial layer –Malabsorption: unabsorbed nutrients & fat –Deranged motitlity: decreased intestinal retention time; decreased motility

DIARRHEAL DISEASE MALABSORPT‏ION SYNDROMES Suboptimal absorption of different nutrients, electrolytes &/or water as a result of disturbance in intraluminal digestion, absorption, terminal (brush border) digestion &/or transepithelial transport. Suboptimal absorption of different nutrients, electrolytes &/or water as a result of disturbance in intraluminal digestion, absorption, terminal (brush border) digestion &/or transepithelial transport. Digestion of food occurs mostly in stomach & small intestine, while absorption occurs mostly in duodenum & jejunum Digestion of food occurs mostly in stomach & small intestine, while absorption occurs mostly in duodenum & jejunum Malabsorption may be caused by a variety of diseases Malabsorption may be caused by a variety of diseases Small intestinal biopsy is an important diagnostic tool: may show characteristic findings, normal or nonspecific changes Small intestinal biopsy is an important diagnostic tool: may show characteristic findings, normal or nonspecific changes c/o weight loss, anorexia, abdominal distension, muscle wasting and passage of abnormally bulky, frothy, greasy, yellow or gray stools (steatorrhea) c/o weight loss, anorexia, abdominal distension, muscle wasting and passage of abnormally bulky, frothy, greasy, yellow or gray stools (steatorrhea)

CONSEQUENCES OF MALABSORPT‏ION SYNDROMES Anemia: iron, pyridoxine, folate or vit. B12 deficiency Anemia: iron, pyridoxine, folate or vit. B12 deficiency Bleeding: vitamin K deficiency Bleeding: vitamin K deficiency Osteopenia & tetany: Ca, Mg, vitamin D deficiency Osteopenia & tetany: Ca, Mg, vitamin D deficiency Amenorrhea, impotence, infertitlity: generalized malnutrition Amenorrhea, impotence, infertitlity: generalized malnutrition Hyperparathyroidism: Ca & vitamin D deficiency Hyperparathyroidism: Ca & vitamin D deficiency Purpura & petechiae: vitamin K deficiency Purpura & petechiae: vitamin K deficiency Edema: protein deficiency Edema: protein deficiency Dermatitis & hyperkeratosis: vit A, Zn, eFA, niacin Dermatitis & hyperkeratosis: vit A, Zn, eFA, niacin Mucositis: vitamin deficiencies Mucositis: vitamin deficiencies Peripheral neuropathy: vit A & B12 deficiency Peripheral neuropathy: vit A & B12 deficiency

CLASSIFICATION OF MALABSORPT‏ION SYNDROMES Defective intraluminal digestion: pancreatic insufficiency; Z-E syndrome; defective bile secretion due to biliary obstruction, hepatic or ileal dysfunction; bacterial overgrowth Defective intraluminal digestion: pancreatic insufficiency; Z-E syndrome; defective bile secretion due to biliary obstruction, hepatic or ileal dysfunction; bacterial overgrowth Mucosal cell abnormalities: lactose intolerence, bacterial overgrowth, abetalipoproteinemia Mucosal cell abnormalities: lactose intolerence, bacterial overgrowth, abetalipoproteinemia Reduced small intestine surface: Celiac sprue, Crohn ’ s,short – gut syndrome Reduced small intestine surface: Celiac sprue, Crohn ’ s,short – gut syndrome Lymphatic obstruction: lymphoma, tuberculosis Lymphatic obstruction: lymphoma, tuberculosis Infection: enteritis, tropical sprue, Whipple ’ s disease Infection: enteritis, tropical sprue, Whipple ’ s disease Iatrogenic: surgeries, drug induced Iatrogenic: surgeries, drug induced