Gastrointestinal Patho Student Notes PDF

THE GASTROINTESTINAL SYSTEM Mary-Ann Cyr DNP MSN BSN APRN ACNP-BC Darcy Ulitsch MSN BSN APRN ACNP-BC  THE DIGESTIVE SYSTEM STRUCTURE FUNCTION PATHOPHYSIOLOGICAL ALTERATIONS  GASTROINTESTINAL SYSTEM...

THE GASTROINTESTINAL SYSTEM Mary-Ann Cyr DNP MSN BSN APRN ACNP-BC Darcy Ulitsch MSN BSN APRN ACNP-BC  THE DIGESTIVE SYSTEM STRUCTURE FUNCTION PATHOPHYSIOLOGICAL ALTERATIONS  GASTROINTESTINAL SYSTEM STRUCTURE The GASTROINTESTINAL SYSTEM is comprised of: GI tract or alimentary canal - Series of hollow organs separated by sphincters running from the mouth to the anus - Four layers - Enteric nervous system Accessory organs - salivary glands - liver - pancreas - gallbladder  GI SYSTEM FUNCTION The basic function of the GI system is to breakdown large macromolecules (proteins, fats, & starches) into smaller molecules that can be absorbed across the canal wall into the circulation. Function is achieved through a series of mechanical & enzymatic processes Secretion – Enzymes, mucus, and ions are secreted by the accessory organs directly into the canal. Motility – contraction of smooth muscle in the wall of the canal that crush, mix and propel its contents forward Absorption – water, ions, and nutrients are transported across the epithelial wall of the canal into blood vessels & eventually the systemic circulation.  MOUTH & ESOPHAGUS STRUCTURE The MOUTH is the site of MASTICATION The ESOPHAGUS is a hollow muscular & mixing of food with saliva tube that transports food bolus from 32 permanent teeth oropharynx to stomach. tongue SWALLOWING begins in oropharynx (voluntary phase, 1-2 sec) hard & soft palate and continues involuntarily (8-10 sec) taste buds in the esophagus exposure to saliva The site of primary & secondary PERISTALSIS; coordinated contraction & relaxation of striated muscle & Taste & food odors stimulate CN I & sphincters help initiate salivation & secretion of Neural & hormonal stimulation gastric juice in stomach CLEFT LIP / PALATE  SALIVARY GLANDS Parotids – secrete watery saliva which lubricates the food bolus and contains immunoglobulins which fight incoming microorganisms & α-amylase which digests starches/complex carbohydrates Submandibulars – secrete a viscous saliva containing the glycoprotein, mucin which lubricates the food bolus *Tubarials – a new pair of salivary glands identified in 2020, Sublinguals – secretes a mucin rich saliva which acknowledged in McCance’s also contains buffering substances Patho book. - located in the torus tubarius, a section in the nasopharynx  STOMACH STRUCTURE STOMACH – J-shaped pouch connecting the esophagus to the small intestine Functional portions: -Cardia: the superior portion where the esophagus enters -Fundus: the superior, dome-like, highly accommodating portion that receives the food bolus & undergoes receptive & adaptive relaxation. receivemore food expands -Body: the curve of the “J” that contains most of the gastric glands which secrete acid & enzymes that kill bacteria & begin digestion of proteins by the enzyme pepsin -Antrum: connects the body to the pyloric region -Pylorus: the curved base where CHYME is propelled into the duodenum through the pyloric valve tubefeedinginsertedPASTpyloricvalveto vomit aspiration Q PYLORIC STENOSIS Caused by hypertrophy & hyperplasia of gastroduodenal junction Surgical intervention may be required  ABDOMINAL CAVITY PERITONEUM: MESENTERY: Serous membrane around A serous fold of peritoneum that lines the abdominal organs & pelvic cavity abdominal cavity & covers most Analogous to pericardium & abdominal organs. pulmonary pleura Continuous, but segmented, from Visceral & parietal layers esopho-gastric to anorectal junction Peritoneal cavity Provides a conduit for lymphatics, blood vessels, & nerves OMENTUM: Mechanical support, allows for Intraabdominal organ composed of movement, stores fat adipose tissue Recently redefined as an organ from Greater & Lesser compartments which all abdominal digestive organs Fat storage, organ protection, develop & maintains them in systemic immune regulation, infection continuity in adulthood. control, wound healing, tissue Excess adipose tissue here, is associated regen…. with metabolic & inflammation  THE ALIMENTARY CANAL STRUCTURE The innermost mucosa is lined with epithelial cells on its canal surface and contains blood vessels that absorb nutrients transported from the canal through the epithelium. The submucosa contains larger blood vessels, lymph vessels, & nerve plexuses, & provides support for mucosal layer. The muscularis externa layer contains smooth muscle & provides peristaltic propulsion of food The outermost layer, serosa, is a thin serous membrane with a layer of connective tissue lines by a layer of mesothelium.  DuodenalUlcer AboveLigamentof Trits SMALL INTESTINE Poster.tt UpperGIbllldtBelowligamentof bleed STRUCTUREusually or trites Lower Gb A pylori DUODENUM: receives the food bolus from the stomach and digestive enzymes from the liver, pancreas, & gallbladder with the primary function of mixing the two. fÉMÉ secretin Bicarb water duotoneutrauzeacidicenvirosolisaceao.ec - Enzymes are secreted by these accessory organs into ducts which join at the ampulla of vater to deliver secretions directly opens into the duodenum. Secretion is controlled by the surrounding muscle or sphincter of oddi. into prevents reflux sluggish so as to pancreas etc tabsorption CCKreleased30minaftermeal relaxsofoddi.ec n12min  SMALL INTESTINE Divisions of the small intestine continued: JEJUNUM: the most functionally significant division 🡪 bile salts from the liver and gallbladder, pancreatic enzymes complete the digestion of proteins, fats and carbohydrates. absorption of digested carbohydrates, lipids, proteins, & simplified nutrients from the intestinal lumen into local blood stream. SAfor absorpintimesofneed ILEUM: the final portion of the small intestine absorbs vitamin B12, bile salts and other nutrients not absorbed in the jejunum. Passes waste products of digestion and undigested particles into the large intestine for excretion. when of gastrin  LARGE INTESTINE STRUCTURE The LARGE INTESTINE divisions: CECUM – collects and begins to compress the contents of the ileum into fecal material, removing and reabsorbing water back into the blood stream COLON – ascending and transverse colon continue to remove water and compress wastes products into fecal material the descending colon stores stool The sigmoid colon is a muscular final portion capable of moving stool onto the rectum the rectum holds feces until nervous stimulation leads to expulsion through the anus.  LIVER STRUCTURE & FUNCTION The liver is a large organ sitting in the right upper quadrant. It is divided into four lobes: The liver has many functions which can be classified as mechanical filtering, detoxifying, synthetic, metabolic, immunologic, storage, and digestive. - major role in digestion is to produce bile and metabolize nutrients.  LIVER DIGESTIVE FUNCTIONS Bile produced in the liver is secreted into the hepatic duct to ultimately pass into the duodenu where it participates in the metabolism of lipids. All nutrients absorbed from the small intestine are transported to the liver via the portal vein, where they are processed prior to transport into the systemic circulation.  PANCREAS STRUCTURE The pancreas is a slender, elongated organ which sits behind the stomach and along the duodenum. It is divided into the tail, adjacent to the spleen, the body and the head which sits next, to and communicates with the duodenum. The pancreatic duct joins the common bile duct to empty pancreatic secretions into the duodenum via the ampulla of vater.  PANCREAS STRUCTURE The pancreas is covered by a thin connective tissue capsule which projects inward as a septa that separates the gland into lobules. Each lobule contains a grapelike cluster of acini (singular for acinus one cell) Each acinus houses secretory granules containing digestive enzymes. The islet of Langerhans is a distinct collection of specialized cells embedded in clusters in the center of pancreatic lobules.  PANCREAS STRUCTURE Each acinus can be stimulated to release (exocytosis) its secretory granules allowing secretions into its lumen. From the lumen, enzymes will enter gradually enlarging intralobular ducts which eventually form the pancreatic duct. Ducts are lined with specialized ductal cells. The pancreatic duct empties acini secretions/digestive enzymes into the duodenum via the ampulla of vater.  PANCREAS STRUCTURE & FUNCTION The pancreas is considered both an endocrine & exocrine organ. ENDOCRINE PANCREAS: the collection of pancreatic cells that synthesize & secrete hormones into the blood stream – the islets of Langerhans α-cells – glucagon β-cells – insulin δ-cells – somatostatin F or gamma cells - pancreatic polypeptide Epsilon cells - ghrelin  EXOCRINE PANCREAS Composed of the acini & EXOCRINE PANCREAS: 80-85% of the ducts which together pancreas is composed of exocrine cells synthesize, store, & secrete which participate in the digestive functions digestive enzymes into the of the pancreas. duodenum. The final pancreatic secretion into the duodenum is referred to as PANCREATIC JUICES which contain enzymes, bicarbonate, & water  PANCREATIC DIGESTIVE ENZYMES The major digestive enzymes are: 1. synthesized within the pancreatic acini 2. stored in the secretory granules of the acini 3. secretory granules are stimulated by the hormone, CHOLECYSTOKININ (CCK), which is released by duodenal mucosal cells approximately 30 minutes following food ingestion with the presence of fats and amino acids in the second portion of the duodenum. 4. once stimulated, the secretory vessels move toward the lumen where they undergo exocytosis, releasing their contents into the acini lumen.  PANCREATIC DIGESTIVE ENZYMES The major enzymes synthesized in the pancreas are classified as: 1. PROTEASES: trypsin & chymotrypsin - function to complete the digestion of proteins that began in the stomach. - corrosive to all tissue/cells with several mechanisms in place to protect the pancreas from destruction packaging of inactive precursors (zymogens), into secretory granules Trypsin inhibitor contained in granules Unidirectional flow achieved by sphincter of oddi  TRYPSIN & CHYMOTRYPSIN TRYPSIN and CHYMOTRYPSIN are synthesized and packaged into granules as the inactive proenzymes, TRYPSINOGEN and CHYMOTRYPSINOGEN. Once secreted into the duodenum, the activation of trypsinogen is stimulated by the hormone, ENTEROKINASE which is secreted from the duodenal wall in response to ingested food entering the duodenum. Once activated trypsinogen activates chymotrypsin and several other enzymes causing an explosion of active proteases into the small intestine. Proteases break proteins down to peptides which are further degraded into single amino acids by PEPTIDASE located on the surface of small intestine epithelial cells.  PANCREATIC DIGESTIVE ENZYMES 2. LIPASE functions to digest triglycerides into monoglycerides and free fatty acids which are capable of being absorbed into the blood stream. 3. α-AMYLASE functions to digest starch which is a major dietary carbohydrate -hydrolyses starch to disaccharides, trisaccharides & fragmental dextrans. - synthesized & secreted from the salivary glands, pancreas and colon.  DUCTAL CELL SECRETIONS Bicarbonate is secreted from acinar cells and bicarbonate and water are secreted by ductal epithelial cells into the ductal lumen as pancreatic enzymes pass, to complete the final contents of the pancreatic juice. Secretin, a hormone produced in the s-cells of the duodenal mucosa, is secreted in response to a low pH and products of protein digestion. It acts to increase secretion of bicarbonate and water from the ductal cells.  ENDOCRINE CONTROL OF PANCREATIC EXOCRINE SECRETIONS Pancreatic secretions are controlled by both endocrine & neural stimulation. regulation results in minimal secretion between food ingestion & maximal secretion when food enters the stomach and then moves into the small intestine. Endocrine regulation: 1. cholecystokinin (CCK) 30 min meal after slow IS for gastricempty Odd bile duo – secreted by endocrine cells in duodenum in response to fats & partially digested proteins. - binds to receptors on acinar cells to stimulate the synthesis & secretion of digestive enzymes. 2. secretin - secreted from endocrine cells in the duodenum in response to low pH fluid & partially digested proteins entering the duodenum - stimulates acinar & ductal cells to secrete bicarbonate & water into the ductal lumen to flush pancreatic enzymes through the ducts and neutralize duodenal fluid. 3. gastrin - secreted in large amounts by the stomach in response to distention and irritation - stimulates acid secretion by parietal cells -stimulates acinar cells to secrete digestive enzymes  NEURAL CONTROL OF PANCREATIC EXOCRINE SECRETIONS The pancreas is innervated by preganglionic parasympathetic nerve fibers of the vagus nerve The vagal nerve fibers provide a low level of stimulation which can induce digestive enzyme and hormonal secretion with even the anticipation of a meal Sympathetic stimulation inhibits pancreatic secretions Hormonal stimulation predominates over the lower-level neural stimulation  SPHINCTER OF ODDI Located at the second portion of the duodenum Smooth circular muscle around: 1. the common channel formed by the pancreatic and bile duct 2. the main pancreatic duct 3. the common bile duct Longitudinal muscle fibers lie between the bile and pancreatic ducts Rhythmic contractions create a pressure greater than that in the common bile and pancreatic duct -resists flow of pancreatic juice and bile into the duodenum between food ingestion so that the duodenal mucosa is not destroyed Stimulation of the sphincter by CCK causes relaxation and so flow into the duodenum -simultaneously CCK stimulates acinar secretion of pancreatic enzymes and gallbladder to contract to release bile Stomach & small intestine contraction is stimulated by the hormone MOTILIN which also stimulates the sphincte of oddi to increase frequency and amplitude of contraction simultaneously. - Backflow of secretions is prevented. In between duodenal contractions, the sphincter relaxes to allow flow into the lower pressure duodenum. Dysfunction of the sphincter usually causes abdominal pain after eating with a back up of pancreatic secretions into the pancreas resulting in inflammation and pancreatitis GI BLOOD SUPPLY GI VENOUS SYSTEM  ABDOMINAL PAIN Acute vs Chronic Generalized vs Localized vs Radiating Sharp vs Dull vs Colicky Structures not sensitive to laceration or crush Sensitive to distention/stretching of structures because of: Mechanical process Inflammation Ischemia Parietal: Peritoneum, localized & intense Visceral: Organs, diffuse & vague Radiating: Visceral felt in localized distal structure MS cooladiaphoretic severepain altered abddist ascites  VOMITING VOMITING or EMESIS: Forceful expulsion of GI contents, usually gastric or proximal small bowel, through the mouth. NAUSEA 🡪 🡪 🡪 RETCHING 🡪🡪🡪 VOMITING ↓ gastric motility Spasmodic respiratory movements Stomach contracts with closed Reverse peristalsis with intermittent glottis closure glottis. 🡪 Diaphragm & abdominal and contraction of abd muscles & muscles contract 🡪 Esophagus stomach contract moves into thorax as its sphincters open **Projectile vomiting occurs without nausea & retching  EMESIS MANAGEMENT Center for vomiting lies in the medulla oblongata which are stimulated by: CHEMORECEPTOR TRIGGER ZONE (CTZ): (blood-borne input as uremia, + ↑K , hormones) Extra GI Viscera: (stones in bile duct, heart ischemia) Extra Medullar Centers: (odors, fears, motion sickness) Stimulation of the EMETIC CENTER results in physical mechanisms of vomiting Many antiemesis medications inhibit vomiting by acting on the CTZ  CONSTIPATION CONSTIPATION is an individualized decrease in the frequency of defecation or increased difficulty in passing stools causing abdominal distention and possibly obstruction. iron NSAIDs anticholinergic opioid inducedantides CAUSES: Low residue/fiber diet Dehydration fluid Lack of exercise dec medabsorp Repeated suppression of urge to defecate Decreased colonic/anus motility Pelvic floor dysfunction Big reason Neurologic diseases (MS Parkinson’s SCI) stroke Narcotics, antacids Pregnancy Constipation dominant IBS exercise Aging Pain cobalxteal alcohol Endocrine disease (Hypothyroidism, DM) Congenital (Hirchsprung’s with missing colonic nerve cells) Neoplasm SC defects  CONSTIPATION MANAGEMENT 3 BMS WK MANIFESTATIONS: Nausea trouble passingstool Vomiting Dx of exclusion Cramping / colicky pain Palpation tenderness Hemorrhoids / bleeding Bloating Distendedabd Overflow diarrhea Obstruction Perforation stool sepsis shockdeath perineum Delayeddigestion a absorption too TREATMENT: Bulk forming laxatives (Psyllium) Stimulant laxatives (Senna, enemas, suppositories, stimulate nerves in colon/rectum) Osmotic laxatives (Lactulose, osmotic draw of fluid into colon) Fecal softeners (Colace) Tamanna unintendweight015 CA s mam evalutherif abd distention 8,00 impact  DIARRHEA DIARRHEA is an individualized increase in frequency, volume and/or fluid consistency of stool. usually infen caused The pathology of diarrhea can produce large volume or small volume diarrhea OSMOTIC DIARRHEA produces a large volume of stool as an undigested substance draws excess fluid into the bowel. ceases w fasting -magnesium, phosphorous, sorbitol, tube feeding, dumping syndrome milk SECRETORY DIARRHEA produces large volume diarrhea from mucosal secretion of excess chloride, or bicarbonate – rich fluid or inhibition of Na+ absorption. -rotavirus, ecoli enterotoxin, excess c-difficile exotoxin after antibiotics which all secrete neurotransmitters that stimulate altered mucosal secretion which lead to ↓water absorption produces small volume diarrhea with inflammation ultimately increasing motility -ulcerative colitis, crohn’s, overflow diarrhea MOTILITY DIARRHEA produces decreased transit time & digestion.  DIARRHEA MANAGEMENT Complications: Treatments: Dehydration IV fluid resuscitation Metabolic acidosis Electrolyte replacement Hyponatremia Correction of acid-base balance Hypokalemia Antimotility agents (opiate or atropine) Weight loss Water absorbent agents Cramping pain Probiotics controversial Bleeding Potostay PO vancomycin/flagyl for c difficile inatanot Fecal transplantation esp recurrent systemic go needto monitorius C Diff i dont  GASTROINTESTINAL BLEEDING Gastrointestinal bleeding is bleeding that begins within the GI tract in any location, mouth to anus. The basic pathophysiology primarily entails the breakdown of mucosa and exposure of submucosa & vessels to erosive HCL acid. MANIFESTATIONS: Hypovolemia / shock Anemia Malnutrition Elevated blood urea nitrogen (BUN) Aspiration pneumonitis TREATMENT: Blood transfusion Duodenal ulcer 2ⁿᵈ Fluid resuscitation Source control 1 Iron repletion Esophageal varices  melena UPPER GI BLEED more common proximal to ligament of Treitz from BUNelevatedover CAVI be loom OROPHAYNGEAL: disaffected ESOPHAGEAL: Inflammatory esophagitis (reflux, chemical, eosinophilic)rome Barrett’s (distal squamous cells undergo metaplasia to Barrett cells & goblet cells ↑ing risk of adenocarcinoma) P Varices (venous bleed from varices of portal HTN) Mallory-Weiss tears (esophageal-gastric junction tears in F mucosa from vomiting, cough, retching) Tumors Dental Injury / perforation DUODENAL: Ulceration (H pylori primary location) GASTRIC: Math9UhYdf9fp creantariatinesoa maturefrom Erosive gastritis (excess HCL, NSAIDs, ASA, steroids, smoking, stress) nestul Ulceration (same risk factors as gastritis & H pylori) even slight cough Can to Mass lesions (vascular endothelial hyperplastic polyps & tumors) denser airway May be due Angiodysplasia (elastic dilation & thinning of vessel walls) intermitdmblled elderly w opain  2 G LOWER GI BLEED LGIBs involve disturbance of mucosa … distal to ligament of Treitz CAUSES: Polyps *MELENA: dark stools Diverticulosis containing blood from Ulcerative Colitis UGIB Malignancies Ulcerations Hemorrhoids Aorto-enteric Fistula **BRIGHT RED BLOOD PER RECTUM (BRBPR): from LGIB  GI BLEED DIAGNOSIS APPEARANCE: stool always moves out DIAGNOSTICS: as it is irritating & increases Occult blood: slow, chronic loss only visible peristalsis with hemoccult testing Melena dark stools containing blood CT, MRI, X-ray less helpful from an UGIB Endoscopy for UGI source Colonoscopy for LGI source BRBPR indicates LGIB Capsule endoscopy for small bowel source Hematemesis indicates acute UGIB Angiography with possible embolization Coffee ground emesis indicates earlier Bleeding scan (tagged RBC) UGIB Barium swallow (upper GI series) Barium enema (lower GI series) Serum studies: CBC, metabolic panel, coagulation studies, ABG, lactate  BOWEL OBSTRUCTION BOWEL OBSTRUCTION results in the partial or complete failure of food, gas, & fluid to move through the small and/or large intestine. MANIFESTATIONS: Bowel distention Multisystem organ dysfunction from Increased gas from metabolism of retained disseminated inflammatory mediators nutrients by increasing bacteria and Ischemia as vessels become compressed swallowed air. by distension Bloating Necrosis & perforation Colicky pain as peristaltic waves reach the obstruction & recede, more intense & constant 10 Sepsis/shock as bacteria leak from damaged tissue into peritoneal space with ischemia/necrosis & perforation or circulation Stimulation of nausea & vomiting centers in Dehydration & electrolyte imbalances as medulla fluid & electrolytes move into the lumen Constipation / diarrhea without reabsorption, sequester into Inflammation of the bowel wall inflamed intestinal wall Hypovolemia/shock Fecal breath odor Altered bowel sounds: high-pitched→ 213PMHabdsurgeryhaveadhesions decreased/absent ABOVEstricturedilates Below collapses  MECHANICAL ETIOLOGY OF BOWEL OBSTRUCTION ADHESIONS or fibrous bands that adhere portions of the bowel together usually forming after trauma or surgery INTUSSUSCEPTION or telescoping of a portion of intestine Sloughed mucosa & mucous into another, most commonly at ileocecal junction of infants TUMOR HERNIA or protrusion of intestine through abdominal wall VOLVULUS or a twisting of intestine around a fixed point  PARALYTIC ILEUS PARALYTIC ILEUS is a functional, pseudo bowel obstruction caused by the failure of food, gas, & fluids to pass without structural abnormalities but rather partial or complete arrest of peristalsis of a portion of the intestine. common insicus ETIOLOGIES: Intra-abdominal surgery/trauma Narcotics Hypokalemia slowweakencontractions Peritonitis Spinal cord injury Pneumonia Neuropathies & myopathies OGILVIE’S SYNDROME is a paralytic ileus with colon distension > 8 cm Utually large BOWEL OBSTRUCTION MANAGEMENT NGtubeto complete Elfin abd XR stop narcotics chewing gumto motility d stem inhib inflam via cephalocaudalreflex Regan mobility the notreeusedalot  IRRITABLE BOWEL SYNDROME Irritable Bowel Syndrome is a condition characterized by: Diagnosis of exclusion Lower abdominal pain Diarrhea, constipation or alternation between both Nausea Bloating Fecal urgency Symptom relief post defecation Often associated with anxiety/depression Without structural abnormality. Pathophysiology involves some combination of: Visceral hyperalgesia esp. with rectal distention Abnormal intestinal permeability, motility & secretion Post infectious with + stool culture Overgrowth of intestinal flora Food allergies/intolerances Psychosocial factors such as emotional stress Treatment involves symptom control: Laxatives, diet, probiotics, antimotility agents, Selective Serotonin Reuptake Inhibitors for pain control  INFLAMMATORY BOWEL DISEASES Chronic inflammation in the bowel with relapsing & remitting patterns with a common pathology INTESTINAL EPITHELIAL CELLS (IEC): ENTEROCYTES nutrient absorption & secrete immunoglobulins GOBLET CELLS secrete mucus M CELLS immune sensing of luminal bacteria, of peyers patches PANETH CELLS synthesize & secrete antimicrobial peptides & proteins NEUROENDOCRINE release intestinal hormones or peptides EXOCRINE CELLS secrete mucus, sucrose, enzymes ENDOCRINE CELLS secrete CCK & Bacteria line intra-lumen mucosa secretin  INFLAMMATORY BOWEL DISEASE PATHOPHYSIOLOGY Several factors contribute to IMPAIRED BARRIER FUNCTION & the TRANSLOCATION OF BACTERIA. Macrophages present antigen to activate CD4 T cells 🡪 the T cells further activate macrophages & 🡪 release cytokines: (IL1, IL6, & TNF alpha) TNF alpha contributes most significantly: Angiogenesis Paneth cell necrosis IEC necrosis Increased immune response Myofibril protease release which further destroys local cells & barriers. During remitting phases cellular regeneration is attempted but not completely normal.  IBD MANAGEMENT DIAGNOSIS: TREATMENT: MANIFESTATIONS: CBC Diarrhea B12 / iron (malabsorption) Rectal bleeding Albumin Abdominal pain C reactive protein Tenesmus (inflammation) Stool culture (r/o C Diff) Weight loss Colonoscopy Vomiting Biopsy (eval for chronicity) Fever Muscle spasms Intestinal cramping Conjunctivitis 20 cytokine release Mesenteric / portal vein thrombosis Uveitis, iritis, scleritis Venous thrombosis Perforation Liver abscess Colon cancer  ULCERATIVE COLITIS VS CROHN’S DISEASE ULCERATIVE COLITIS and CROHN’S DISEASE share a similar pathophysiology yet are distinct inflammatory bowel disease. UC: Begins in rectal & CD: sigmoid colon 🡪 Ileocecal, sm. intestine ascends to the desc. patchy transmural colon (Lt colitis or inflammation in a transverse colon = skip lesion pattern extensive colitis) *Affecting superficial mucosa *Unique complications: *Unique complications: stenosis, abscess, fistula extensive bleed, toxic megacolon  CHOLECYSTITIS Inflammation of the gallbladder is most often associated with gallstones comprised of bilirubin, cholesterol, or both. ACUTE CHOLECYSTITIS typically involves obstruction of flow of bile from gallbladder to duodenum because of a stone which has descended into the cystic or common bile duct. Manifestations: Fever Leukocytosis Rebound tenderness Guarding RUQ pain –radiating to the right shoulder Colicky – postprandial *As the gallbladder becomes gallbladder contractions distended & inflamed, distension intensifies pain of the inflamed may lead to ischemia, necrosis, & organ perforation  CHRONIC CHOLECYSTITIS & TREATMENT Gallstones may obstruct & recede causing a chronic state of gallbladder wall inflammation. Stones within the organ itself are also a source of chronic contact with the gallbladder wall causing constant inflammation. Over time, the epithelial cells of the GB wall change morphology & eventually become fibrotic & calcified. TREATMENT: IV fluids & electrolyte replacement Analgesia NPO Antibiotics in severe cases Cholecystostomy tube Cholecystectomy laparoscopic vs. open ACUTE PANCREATITIS MANIFESTATIONS: Pain Fever Leukocytosis Nausea, vomiting/paralytic ileus SIRS ARDS / hypoxemia Renal Failure / prerenal TREATMENT: Analgesia; Demerol- less sphincter of Oddi spasm IV fluids Respiratory/Oxygen support Vasopressors J tube feeding / past LOT Surgical resection if necrotic  CHRONIC PANCREATITIS CHRONIC PANCREATITIS, most commonly cause by alcohol abuse, occurs after repeated episodes of acute pancreatitis. - Acinar cells & islets of Langerhans are destroyed by chronic inflammation - Those cells are replaced by fibrous tissue, calcifications, ductal obstruction, & cysts - Cysts are walled off necrotic debris, pancreatic juice, & blood. - Those with chronic pancreatitis have an increased risk of developing DM & pancreatic cancer TREATMENT: Analgesia, non-opioid & oral lipase Small, frequent, low-fat meals Fat-soluble vitamins Alcohol cessation Insulin Cyst drainage & resection Pancreatic ductal stent with drainage LIVER STRUCTURE  LIVER LOBULES - Epithelial cells are fenestrated to allow lymph & protein to pass - Stellate cells store vitamin A  LIVER FUNCTION HEPATOCYTES function to: Transamination: synthesis of AA using aminotransferase enzymes (ALT & AST indication of hepatic function) Deamination: metabolism of AA by oxidation in which ammonia group is removed Synthesis of proteins: albumin, opsonin, complement, hormones (thrombopoietin, angiotensinogen) clotting factors, plasma protein carriers (transferrin) Urea production from ammonia and other substances to assist with their excretion Bile production (ambiphillic bile salts for lipid emulsion & bile pigments that are conjugated for elimination) Carbohydrate metabolism: Glycogenesis glucose to glycogen Glycogenolysis to glucose Gluconeogenesis pyruvate (from AA, fats) to glucose Produces lipids / lipoproteins Produce phospholipids Produce cholesterol  LIVER INJURY Hepatocytes can undergo reversible or irreversible injury leading to apoptosis or necrosis. Acute liver injury is reversible but can result in largescale hepatocyte necrosis which can lead to acute or fulminant liver failure. Chronic Injury is irreversible, prolonged injury, or repeated acute liver injury with recovery leading to the intermediate stage of cirrhosis which can progress to chronic liver failure.  ACUTE OR FULMINANT LIVER FAILURE Acute Liver Failure involves acute loss of hepatocellular function within days to weeks as a result of necrosis in the absence of underlying liver disease. Manifestations Causes Jaundice or viral (Hepatitis A, B, C) hyperbilirubinemia Drugs (Acetaminophen OD) Encephalopathy with cognitive deficits & asterixis (hallmark) 2 0 ammonia Viral (CMV, Hepatitis) Coagulopathy Pregnancy Liver dysfunction is lost when >90% hepatocytes are lost / necrosis / liver is atrophied Regeneration can occur if stimulus removed prior to 90% lost cells as hepatocytes become mytotic through release of mediators such as hepatocyte growth factor. Fibrosis does not occur if regeneration is possible.  ACETAMINOPHEN TOXICITY Acetaminophen produces a toxic metabolite, N-acetyl Para benzoquinone (NAPQI) through oxidation & an intermediate free radical The liver also produces GLUTATHIONE, an antioxidant which inactivates the metabolite. In OD glutathione stores are depleted allowing accumulation of NAPQI which leads to hepatocyte necrosis. TREATMENT: *antidote* N-acetylcysteine (NAC), provides cysteine for glutathione synthesis, acts as a substitute for glutathione & prevents binding of NAPQI to hepatic macromolecules  LIVER CIRRHOSIS Chronic liver disease can progress from COMPENSATED CIRRHOSIS to an UNCOMPENSATED CIRRHOSIS to CHRONIC LIVER FAILURE COMPENSATED (asymptomatic) CIRRHOSIS becomes UNCOMPENSATED (symptomatic) CIRRHOSIS when a complication develops: COMPLICATIONS (uncompensated): Cirrhosis = fibrosis Encephalopathy Jaundice T Chronic liver failure = Loss of function over time Variceal bleeding Ascites *Both types are at increased risk for development of hepatic carcinoma Causes of CIRRHOSIS: Chronic Hepatitis B or C Alcoholic or nonalcoholic fatty liver Wilson’s disease  CIRRHOSIS PATHOPHYSIOLOGY PATHOPHYSIOLOGY: Diffuse fibrosis Any chronic injury stimulates Kupffer cells to secrete: TGF beta growth factor that converts stellate cells into myofibroblasts Endothelin 1 which fosters myofibroblasts contract for the release of large amounts of collagen to form fibrous septra Parenchymal nodules with regenerative hepatocytes Vascular shunting occurs when collateral veins develop to transport blood from GI organs directly into the IVC. Pressure within the collaterals results in esophageal varices, hemorrhoids, & caput medusae  CIRRHOSIS COMPLICATIONS Portal hypertension increased resistance to flow \ increased flow dilatation of GI arteries by nitric oxide Ascites increased portal & hydrostatic pressure, lymph enters space of Disse 🡪 thoracic duct, RAAS is activated 🡪 fluid retention + hypoalbuminemia 🡪 fluid leaks out into peritoneum low proteinIVI lox sponperitonitis Splenomegaly increased congestion in portal system 🡪 engorged spleen, hypersplenism 🡪 active pancytopenia from sequestering blood cells Infections spontaneous bacterial peritonitis Klebsiellafrom GItract Increased estrogen palmar erythema, gynecomastia, & spider angioma accum E Jaundice hyperbilirubinemia serum br Hemorrhage varices belivercant Hepatorenal syndrome prerenal Hepatopulmonary hypertensionPWKI E Coagulation disorders made Hepatic encephalopathy CATscanto seeperforations  CIRRHOSIS COMPLICATIONS Portal Hypertension: Increased pressure in the portal system of the liver caused by resistance to flow into the liver or Increased flow from arterial system into the liver (vasodilatation of arteries supplying the GI organs)  CIRRHOSIS COMPLICATIONS Ascites is an accumulation of excess fluid in the peritoneal cavity generally caused by increased hydrostatic pressure in lymph and blood vessels compounded by hypoalbuminemia.  CIRRHOSIS COMPLICATIONS Splenomegaly occurs when the spleen enlarges to accommodate retained blood flow. Hypersplenism occurs as cells become overactive producing pancytopenia. Estrogen levels are increased when it can no longer be eliminated by the liver Palmar erythema Gynecomastia Spider Angiomas CHRONIC LIVER FAILURE MANAGEMENT  GROUP WORK QUESTIONS & REVIEW Case study: A & P: Acetaminophen Toxicity Stomach, S. of Oddi Small intestine, CCK… Constipation & diarrhea GI Bleed Bowel Obstruction Cirrhosis QUESTIONS & REVIEW & GROUPS  GI CASE STUDY (ALL GROUPS) Paul is a 19-year-old college student who is preparing to try out for the varsity football team. Ten days before tryouts he sprains his back practicing with his friends. He is extremely concerned about the possibility of missing tryouts, so he goes to see his primary care physician. He is prescribed Endocet 5.5/500 mg, two tablets twice daily. His physician assures him that this will treat both his acute inflammation and pain. Paul wants to get better and be able to continue his preparation for tryouts, so he also takes three extra-strength acetaminophen, every four hours. He regretted giving himself the weekend off before his injury. He slept in on both days of that weekend and went to a great party on Saturday night. Though he drank more than he should have, he knew he had all day on Sunday to recover and that he was going to get back to intense football training on Monday, the day he sustained his injury. By Wednesday, after over 24 hours of treatment, he began feeling much better. He woke up on Friday morning feeling nauseated and sweaty, like he had the flu. That evening his mother brought him to the emergency department after he became lethargic and confused. On physical examination, Paul's liver was tender and mildly enlarged. His liver function tests showed acute liver failure. After several weeks of treatment, his liver function tests normalized. Unfortunately, he had to put his dream of playing varsity football on hold until next year.  GI CASE STUDY (ALL GROUPS) Question 1: How many grams of acetaminophen was Paul ingesting per day? Question 2: What is the recommended maximum daily dose of acetaminophen? Question 3: What is the pathophysiology of liver failure associated with acetaminophen toxicity? Question 4: What metabolic factors may have influenced Paul’s acetaminophen toxicity? Question 5: What is your plan for Paul? Be specific with medication (dose, indication, mechanism of action...). Consults? Referrals?