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PATHOPHYSIOLOGY PATHOPHYSIOLOGY OF OF

GASTROINTESTINAL GASTROINTESTINAL SYSTEM DİSORDERSSYSTEM DİSORDERS

Mehtap KAÇAR KOÇAK M.D. PhDMehtap KAÇAR KOÇAK M.D. PhD

PathophysiologistPathophysiologist

Yeditepe University, Faculty of Yeditepe University, Faculty of MedicineMedicine

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OverviewOverview• Common Manifestations of Digestive System Common Manifestations of Digestive System

DisordersDisorders• Anorexia, nausea, vomitingAnorexia, nausea, vomiting• DiarrheaDiarrhea• ConstipationConstipation• PainPain• MalnutritionMalnutrition

• Basic Diagnostic TestsBasic Diagnostic Tests• Common TherapiesCommon Therapies• Upper Gastrointestinal Tract DisordersUpper Gastrointestinal Tract Disorders

• Eusophagial disordersEusophagial disorders• GastritisGastritis• Peptic ulcerPeptic ulcer

• Lower Gastrointestinal Tract DisordersLower Gastrointestinal Tract Disorders• Inflamatuar Bowel DiseasesInflamatuar Bowel Diseases

• Disorders of the Liver and PancreasDisorders of the Liver and Pancreas• Gallbladder disordersGallbladder disorders• HepatitisHepatitis• PancreatitisPancreatitis

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Common Manifestations—Common Manifestations—Anorexia, Nausea, Anorexia, Nausea,

VomitingVomiting• Digestive system disorders or sign of Digestive system disorders or sign of

other problemsother problems• Nausea and vomiting common Nausea and vomiting common

indicators of GI disorderindicators of GI disorder• Anorexia precedes the aboveAnorexia precedes the above

• NauseaNausea• General unpleasant, subjective feelingGeneral unpleasant, subjective feeling

• VomitingVomiting• Forceful expulsion of irritantForceful expulsion of irritant• Medulla coordinates reflexMedulla coordinates reflex

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Steps of VomitingSteps of Vomiting

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Anorexia, Nausea, Anorexia, Nausea, VomitingVomiting

• RetchRetch occurs occurs before vomiting before vomiting..• Characteristics of vomitusCharacteristics of vomitus are are

• ““coffee grounds”coffee grounds”• Contains Contains BloodBlood• Partial digestion in stomach of protein in Partial digestion in stomach of protein in

bloodblood

• Yellowish-greenYellowish-green• Contains bile (from duodenum)Contains bile (from duodenum)

• Deeper brownDeeper brown• Content from lower intestineContent from lower intestine

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Common Manifestations—Common Manifestations—Diarrhea Diarrhea

• It means of eIt means of excessive freqxcessive frequentuent of of stoolsstools..• Stools uStools usually loose and waterysually loose and watery..• It can be aIt can be acute or chroniccute or chronic..

• AccompAccompoinedoined by cramps and pain by cramps and pain• Severe, prolonged may lead toSevere, prolonged may lead to

• Dehydration, electrolyte imbalance, Dehydration, electrolyte imbalance, acidosis, malnutritionacidosis, malnutrition

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Diarrhea—Classification Diarrhea—Classification • LLararggee vol volumeume diarrhea diarrhea

• It can be sIt can be secretory or osmoticecretory or osmotic..• It lIt leads to watery stool (increased secretion eads to watery stool (increased secretion

into intestine)into intestine)• Its oIts often related to infection or short transit ften related to infection or short transit

timetime..• SmSmallall vol volumeume diarrhea diarrhea

• It usually results from iIt usually results from inflammatory bowel nflammatory bowel diseasedisease..

• Stool with blood, mucus, pusStool with blood, mucus, pus• Steatorrhea Steatorrhea

• ““fatty diarrhea”fatty diarrhea”• FreqFrequentuent, bulky, greasy, loose stools with , bulky, greasy, loose stools with

foul odorfoul odor• Characteristic of malabsorption disorderCharacteristic of malabsorption disorder

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Diarrhea—Classification Diarrhea—Classification • Blood

• Frank blood• Red blood on surface of stool

• Lesions in rectum/anal canal• Not been “digested”

• Occult blood• Small hidden amounts• Not visible to eye• Caused by bleeding ulcers in stomach, small

intestine• Melena

• Dark-colored• Significant bleeding higher in digestive tract• Hb acted on by bacteria leads to darker color

• Gas• Develops normally in digestive tract

• From swallowed air and digestion/bacterial action

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Constipation — Constipation — ManifestationsManifestations• Less frequent bowel movements and passage

of small hard stools• Acute or chronic• Can alter with periods of diarrhea• Causes are

• Inadequate dietary fiber• Inadequate fluid intake• Failure to respond to defecation reflex• Muscle weakness and inactivity• Neurologic disorders• Drugs• Some antacids, iron meds, bulk laxatives• Obstruction by tumor

• Chronic can lead to hemorrhoids• Severe can lead to impaction

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Manifestations—Pain Manifestations—Pain • Visceral painVisceral pain

• Pallor, sweating, nausea, vomitingPallor, sweating, nausea, vomiting• Burning sensationBurning sensation

• Inflammation and ulceration in higher digestive Inflammation and ulceration in higher digestive tracttract

• Related to oral ulcerations and heartburnRelated to oral ulcerations and heartburn• Dull aching painDull aching pain

• Higher right quadrantHigher right quadrant• Typical of liver capsule stretchingTypical of liver capsule stretching

• Cramping diffuse painCramping diffuse pain• Characteristic of inflammation, distention, Characteristic of inflammation, distention,

stretching of intestinesstretching of intestines• Colicky severe painColicky severe pain

• Recurrent smooth muscle spasmRecurrent smooth muscle spasm• Response to severe inflammation/obstuction Response to severe inflammation/obstuction

(ex(exampleample gallstones) gallstones)

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PainPain

• Somatic painSomatic pain• Steady, intense, well-localizedSteady, intense, well-localized• Indicates involvIndicates involveement/inflammation ment/inflammation

of parietal peritoneumof parietal peritoneum• Ex: appendicitisEx: appendicitis

• Referred painReferred pain• May delay diagnosisMay delay diagnosis

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Manifestations—Manifestations—Malnutrition Malnutrition

• Limited or generalLimited or general• SpecificSpecific• General malnutritionGeneral malnutrition

• Chronic anorexia, vomiting, diarrheaChronic anorexia, vomiting, diarrhea

• Diets (“fad diets”)Diets (“fad diets”)• May lack certain reqMay lack certain requireduired elements of elements of

nutritionnutrition

• ChildChild• Growth/development delayedGrowth/development delayed and/or and/or

impairedimpaired

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Basic Diagnostic Tests Basic Diagnostic Tests • RadiographsRadiographs

• X-ray (common wX-ray (common with ith barium)barium)

• UltrasoundUltrasound

• CT and MRICT and MRI• Liver and pancreatic Liver and pancreatic

abnormalitiesabnormalities

• Fiberoptic Fiberoptic endoscopyendoscopy• Improved Improved

visualizations or visualizations or biopsybiopsy

• Lab analysisLab analysis• Stool samplesStool samples

• Blood TestsBlood Tests• Check liver functionCheck liver function

• EvalEvaluateduated serum serum protein levels, clotting protein levels, clotting times, serum liver times, serum liver enzymes, bilirubin enzymes, bilirubin levelslevels

• Pancreatic functionPancreatic function• Serum enzyme levelsSerum enzyme levels• Stool analysis for Stool analysis for

enzyme, fat contentenzyme, fat content

• CEA (carcinoembryonic CEA (carcinoembryonic antigen)antigen)

• Blood tumor markerBlood tumor marker• Colon cancerColon cancer

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Upper Gastrointestinal Upper Gastrointestinal TractTract DisordersDisorders

•Eusophagial disordersEusophagial disorders•GastritisGastritis•Peptic ulcerPeptic ulcer

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• Achalasia is a disease of unknown etiology Achalasia is a disease of unknown etiology that is characterized by the degeneration that is characterized by the degeneration of neural elements in the wall of the of neural elements in the wall of the esophagus. esophagus.

• Achalasia ("does not relax") - loss of peristalsis in the distal esophagus and a failure of LES relaxation.

• Degenerative changes also can be found Degenerative changes also can be found in ganglion cells of the dorsal motor in ganglion cells of the dorsal motor nucleus of the vagus in the brainstem, and nucleus of the vagus in the brainstem, and Wallerian degeneration has been observed Wallerian degeneration has been observed in vagal fibers that supply the esophagus.in vagal fibers that supply the esophagus.

AchalasiaAchalasia

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PATHOPHYSIOLOGYPATHOPHYSIOLOGY•The disordered esophageal motility of achalasia appears to be due primarily to the degeneration and loss of ganglion cells within the esophageal wall, a process that preferentially affects inhibitory neurons.

•Loss of inhibitory neurons in the LES causes basal sphincter pressures to rise, and renders the sphincter incapable of normal relaxation.

•In the smooth muscle portion of the body of the esophagus, the loss of intramural neurons results in aperistalsis.

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Etiology- Achalasia

• The etiology of achalasia is not The etiology of achalasia is not knownknown

• Autoimmune disorderAutoimmune disorder - - associated with HLA-DQw1 - associated with HLA-DQw1 - antibodies to enteric neurons antibodies to enteric neurons

• Chronic infectionsChronic infections with herpes with herpes zoster or measles viruseszoster or measles viruses

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• Chagas disease Chagas disease (Trypanosoma (Trypanosoma cruzi) can result in cruzi) can result in a loss of intramural a loss of intramural ganglion cells ganglion cells leading to leading to aperistalsis and aperistalsis and incomplete LES incomplete LES relaxation relaxation ..

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• Malignancy - most common cause of pseudoachalasia

• Invasion of the esophageal neural plexuses directly, or part of a paraneoplastic syndrome.

• Other tumors - esophagus, lung, lymphoma and pancreatic carcinoma

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• Patients who have a clinical history suggestive of achalasia require radiographic, manometric, and endoscopic evaluation to confirm the diagnosis.

• A barium swallow - A barium swallow - diagnostic accuracy is diagnostic accuracy is approximately 95%approximately 95%

• Absence of peristalsisAbsence of peristalsis

• In some patients, spastic In some patients, spastic contractions in the contractions in the esophageal body esophageal body ("vigorous" achalasia("vigorous" achalasia))

Diagnosis- Diagnosis- AchalasiaAchalasia

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Gastroesophageal Reflux Gastroesophageal Reflux Disease (GERD)Disease (GERD)

• In conjunction with hiatal herniaIn conjunction with hiatal hernia• Severity depends on lower Severity depends on lower

esophageal sphincter (LES)esophageal sphincter (LES)• FreqFrequentuent episodes at night episodes at night• Eliminate factors that decrease Eliminate factors that decrease

LES pressureLES pressure• Avoid spicy foods, take anAvoid spicy foods, take anttacidsacids

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GERDGERD

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Hiatal HerniaHiatal Hernia• Part of stomach elevated, protrudes

thru hiatus of diaphragm into thoracic cavity

• 2 types• Sliding hernia

• More common• Portion of stomach and gastroesophageal

junction move up diaphragm• Esp when supine

• Standing herniated portion slides down into ab cavity

• Rolling (paraesophageal) hernia• Fundus moves up thru enlarged or weak hiatus

in diaphragm• Bv in wall of stomach may be compressed =

ulcers

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Hiatal HerniaHiatal Hernia• Food lodges in pouchFood lodges in pouch

• Inflammation of mucosa, reflex of Inflammation of mucosa, reflex of food up to esophagus, dysphagia food up to esophagus, dysphagia (difficulty swallowing)(difficulty swallowing)

• Often incompetent Often incompetent gastroesophageal sphinctergastroesophageal sphincter

• Contributing factorsContributing factors• Shortening of esophagusShortening of esophagus• Weakness of diaphragmWeakness of diaphragm• Increased abdominal pressure Increased abdominal pressure

(pregnancy)(pregnancy)

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Hiatal HerniaHiatal Hernia

• SignsSigns• Heartburn Heartburn

• Brief substernal burning sensation Brief substernal burning sensation

• FreqFrequentuent belching belching• Discomfort when lying supineDiscomfort when lying supine• Dysphagia commonDysphagia common

• Results ofResults of inflammation of inflammation of esophagus or mass of food in pouch esophagus or mass of food in pouch compresses esophaguscompresses esophagus

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Gastritis includes a myriad of disorders that involve inflammatory changes in the gastric mucosa, including:

1. erosive gastritis caused by a noxious irritant

2. reflux gastritis from exposure to bile and pancreatic fluids

3. hemorrhagic gastritis

4. infectious gastritis

5. gastric mucosal atrophy

GastritisGastritis

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Sex: Sex:

Male-to-female ratio of gastritis is approximately 1:1Male-to-female ratio of gastritis is approximately 1:1

• Male-to-female ratio of PUD is approximately 2:1Male-to-female ratio of PUD is approximately 2:1

An estimated 60% of Americans older than 60 An estimated 60% of Americans older than 60 years harbor years harbor H pyloriH pylori..

Duodenal ulcers usually occur in those aged Duodenal ulcers usually occur in those aged 25-75 years.25-75 years.

Gastric ulcer incidence peaks in those aged 55-Gastric ulcer incidence peaks in those aged 55-65 years.65 years.

Age: Age:

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PathophysiologPathophysiologyy

The mechanisms of mucosal injury in gastritis and PUD are thought to be an imbalance of

aggressive factors

• acid production or pepsin

and defensive factors• mucus production • bicarbonate • and blood flow

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Pathophysiology

• Erosive gastritisErosive gastritis usually is associated with usually is associated with serious illness or with various drugs. serious illness or with various drugs.

Stress, ethanol, bile, and nonsteroidal anti-Stress, ethanol, bile, and nonsteroidal anti-inflammatory drugs (NSAIDs) disrupt the inflammatory drugs (NSAIDs) disrupt the gastric mucosal barrier, making it vulnerable gastric mucosal barrier, making it vulnerable to normal gastric secretions.to normal gastric secretions.

• NSAIDs and aspirin also interfere with the NSAIDs and aspirin also interfere with the protective mucus layer by inhibiting mucosal protective mucus layer by inhibiting mucosal cyclooxygenase activity, reducing levels of cyclooxygenase activity, reducing levels of mucosal prostaglandinsmucosal prostaglandins

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Acute gastritisAcute gastritis

• an acute mucosal inflammatory process, usually of a transient nature

• severe erosive form is an important cause of acute gastrointestinal bleeding

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Acute gastritis

• AAcute gastritiscute gastritis

• AAcute hemorrhagic gastritiscute hemorrhagic gastritis

• AAcute erosive gastritiscute erosive gastritis

• AAcute stress gastritiscute stress gastritis

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CausesCauses H pylori (most common cause of ulceration) NSAIDs, aspirin Gastrinoma (Zollinger-Ellison syndrome) Severe stress (eg, trauma, burns), Curling ulcers Alcohol Bile reflux Pancreatic enzyme reflux Radiation Staphylococcus aureus exotoxin Bacterial or viral infection

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Patients typically present with abdominal pain

that has the following characteristics

Epigastric to left upper quadrantEpigastric to left upper quadrant

Frequently described as burningFrequently described as burning

May radiate to the backMay radiate to the back

Usually occurs 1-5 hours after mealsUsually occurs 1-5 hours after meals

May be relieved by food, antacids (duodenal), or vomiting (gastric)May be relieved by food, antacids (duodenal), or vomiting (gastric)

Typically follows a daily pattern specific to patientTypically follows a daily pattern specific to patient

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Physical examination

Epigastric tenderness is present and usually mild.Epigastric tenderness is present and usually mild.

Bowel sounds are normal.Bowel sounds are normal.

Signs of peritonitis or GI bleeding may manifest. Signs of peritonitis or GI bleeding may manifest. ((Perform a rectal examination and Hemoccult Perform a rectal examination and Hemoccult

testingtesting))

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Differential diagnosisDifferential diagnosis

  Acute Coronary Syndrome

[Aneurysms, Abdominal]Cholangitis Cholecystitis and Biliary Colic Cholelithiasis Diverticular Disease Esophagitis Gastroenteritis Hepatitis Inflammatory Bowel Disease

Mesenteric Ischemia Mesenteric Ischemia

Myocardial Infarction Myocardial Infarction

Pancreatitis Pancreatitis

Pulmonary Embolism Pulmonary Embolism

Renal CalculiRenal Calculi

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Complications:Complications:

MalignancyMalignancy

HemorrhageHemorrhage

PerforationPerforation

ObstructionObstruction

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•Patients should be warned of known or potentially injurious drugs and agents. Some examples are as follows:

o NSAIDs

o Aspirin

o Alcohol

• Caffeine (eg, coffee, tea, colas)

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Chronic gastritisChronic gastritis

• Type A [fundal] gastritisType A [fundal] gastritis

• Type B [antral] gastritisType B [antral] gastritis

[a] hypersecretory gastritis [b] environmental gastritis.

• Hypertrophic gastritisHypertrophic gastritis

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Type A [fundal] gastritisType A [fundal] gastritis

• circulating antibodies to parietal cells and intrinsic factor circulating antibodies to parietal cells and intrinsic factor

• hypo- or achlorhydriahypo- or achlorhydria

• a high intragastric pH and hypergastrinemia a high intragastric pH and hypergastrinemia

• 10% of patients go on develop overt pernicious anemia 10% of patients go on develop overt pernicious anemia

• associated with autoimmune disorders such as associated with autoimmune disorders such as Hashimoto’s thyroiditis and Adison’s diseaseHashimoto’s thyroiditis and Adison’s disease

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Type B [antral] gastritis

• the hypersecretory type - restricted to the antrum - gastric hypersecretion - frequently symptomatic

• the environmental gastritis - the most common form of gastritis in all age groups - irregularly focal involvment of the antral mucosa - gradually extends deeper into the mucosa and

cause mucosal atrophy

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Hypertrophic gastritisHypertrophic gastritis

Three variants are recognizedThree variants are recognized

• Menetrier’s diseaseMenetrier’s disease

• Hypersecretory gastropathyHypersecretory gastropathy

• GGastric gland hyperplasiaastric gland hyperplasia

[[the Zollinger-Ellison syndromethe Zollinger-Ellison syndrome]]

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• Characterized by Giant enlargement of the gastric rugal folds• Caused by hyperplasia of epithelial cells ( not due to inflammation )• ↑risk of cancer• Includes 3 variants• A) Menetrier’s diseaseA) Menetrier’s disease

• Hyperplasia of surface mucous cells • glandular atrophy • excessive loss of proteins in gastric secretion (protein-losing (protein-losing

Gastropathy)Gastropathy)• B) Hypersecretory GastropathyB) Hypersecretory Gastropathy

• HyperplasiaHyperplasia of parietal and chief cells• Secondary to excessive gastrin stimulation.

• C) Zollinger - Ellison SyndromeC) Zollinger - Ellison Syndrome• Caused by Gastrinoma of Pancreas secreting gastrin elevated serum

gastrin levels • multiple peptic ulcerations in stomach, duodenum, jejunum• Hypertrophic rugal folds & Parietal cell hyperplasia excess gastric

acid production

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Peptic Ulcers: Gastric and Duodenal Peptic Ulcers: Gastric and Duodenal UlcersUlcers Pathophysiology Pathophysiology

• Proximal duodenum most common• Also found in antrum of stomach or lower

esophagus• Usually appear as single, small, round

cavities• Smooth margins; penetrate submucosa

• Once acid or pepsin penetrate mucosal barrier tissues exposed to continuous damage• Acid diffuses into gastric wall

• May erode deeply into musculature and eventually perforate wall

• Inflammation surrounds crater

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Gastric and Duodenal Ulcers Pathophysiology

• Erosion invades bv wall, bleeding occurs• Persistent loss of small amt of blood• Or massive hemorrhage

• Development begins w/ break down of mucosal barrier

• Decreased resistance of mucosa or increase HCl or pepsin secretion• Impaired mucosal defenses (gastric ulcer)• Increased acid secretion (duodenal ulcer)

• Most have H. pylori present

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Ulcers—Ulcers—Pathophysiology Pathophysiology

• Mucosal barrier Mucosal barrier damaged by:damaged by:• Inadeq blood supplyInadeq blood supply• Excessive Excessive

glucocorticoid glucocorticoid secretion or meds secretion or meds (Prednisone)(Prednisone)

• Ulcerogenic Ulcerogenic substancessubstances

• Atrophy of gastric Atrophy of gastric mucosamucosa

• Increased acid/pepsin secretion assoc w/• Increased gastrin

secretion• Increased vagal stim or

increased sensitivity to stim

• Increased # acid-pepsin secretory cells in stomach

• Increased stim of acid-pepsin secretion

• Interference with normal feedback mechanism

• Rapid gastric emptying

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Ulcers—Ulcers—Pathophysiology Pathophysiology

• Stress affectsStress affects• Healing is difficultHealing is difficult

• Granulation tissue forms deep in cavityGranulation tissue forms deep in cavity• Breaks down (subject to damage by chyme)Breaks down (subject to damage by chyme)

• Longer healing time = more fibrous Longer healing time = more fibrous tissuetissue

• ComplicationsComplications• HemorrhageHemorrhage• PerforationPerforation• Obstruction Obstruction

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Pathophysiologic mechanism of ulcer

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Ulcers—Signs and Ulcers—Signs and SymptomsSymptoms

• Epigastric burning/aching• 2-3 hours after meals, at night• Cyclic pain relieved by eating

• Heartburn, • nausea,• vomiting

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UlcersUlcersDiagnostic Tests and Diagnostic Tests and

TreatmentTreatment

• TestsTests• Fibroscopic endoscopyFibroscopic endoscopy• Barium X-rayBarium X-ray• BiopsyBiopsy

• TreatmentTreatment• Combo of drugsCombo of drugs

• 2-3 antimicrobial drugs and meds to 2-3 antimicrobial drugs and meds to decrease acid secretiondecrease acid secretion

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SStress ulcerstress ulcers

• ShockShock

• EExtensive burnsxtensive burns

• SepsisSepsis

• TraumaTrauma

• BBrain tumors and following intracranial surgeryrain tumors and following intracranial surgery

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Etiology of stress ulcersEtiology of stress ulcers

Neurogenic or catecholamine-induced vasoconstriction

Mucosal ischemia

Damage the mucosal barrier

Directly injure mucosal cells by oxygen or metabolic deprivation

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SStress ulcerstress ulcers

Those associated with intracranial problems are Those associated with intracranial problems are referred to as referred to as Cushing’s ulcers.Cushing’s ulcers.

Those associated with shock an extensive burns Those associated with shock an extensive burns are referred to as are referred to as Curling’s ulcersCurling’s ulcers..

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Gastroenteritis Gastroenteritis

• It is iIt is inflammation of stomach, intestinenflammation of stomach, intestine• Usually caused by an infectionUsually caused by an infection• Inflammation of gastric mucosa Inflammation of gastric mucosa leads toleads to

vomitingvomiting• Inflammation of intestines causes increased Inflammation of intestines causes increased

motility, impaired absorptionmotility, impaired absorption, it is called , it is called diarrheadiarrhea..

• Nausea and abdominal crampsNausea and abdominal cramps occur. occur.• Microorganism transmitted by contaminated Microorganism transmitted by contaminated

food, water, oral-fecal routefood, water, oral-fecal route• Most infections mild, self-limitingMost infections mild, self-limiting

• Epidemics (common in day-cares)Epidemics (common in day-cares)• Careful hand washing, food-handelingCareful hand washing, food-handeling• Supportive treatmentSupportive treatment

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Pathophysiology of ulcerative Pathophysiology of ulcerative colitiscolitis

• Affects the mucous and the submucosa of the colon and rectum.• Inflamed crypts of Lieberkuhn in the

distal large intestine and rectum.

• Pinpoint microscopic hemorrhages develop.

• Then crypt abscesses develop.

• The abscesses penetrated the superficial submucosa an spread laterally leading to mucosal necrosis and sloughing.

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Pathophysiology of Ulcerative Pathophysiology of Ulcerative ColitisColitis

•The inflammatory process leads to The inflammatory process leads to further tissue damage from exudate further tissue damage from exudate and the release of inflammatory and the release of inflammatory mediators such as prostanglandins mediators such as prostanglandins and cytokines.and cytokines.

•The mucosa becomes red because of The mucosa becomes red because of vascular congestion, friable and vascular congestion, friable and edematous.edematous.

• It bleeds easy and hemorrhage is It bleeds easy and hemorrhage is common.common.

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Pathophysiology of Ulcerative Pathophysiology of Ulcerative ColitisColitis

• Edema obscure the submucosal vessels Edema obscure the submucosal vessels and creates a granular appearance.and creates a granular appearance.

• Pseudopolyps tongue line projections are Pseudopolyps tongue line projections are common.common.

• Polypoid changes represent areas of Polypoid changes represent areas of edematous tissue between areas of edematous tissue between areas of ulceration ..ulceration ..

• Chronic inflammation leads to shortening Chronic inflammation leads to shortening of the colon from fibrosis and loss of of the colon from fibrosis and loss of haustra.haustra.

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Polyps changes that Polyps changes that occur in ulcerative occur in ulcerative

colitiscolitis

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Pathophysiology of Ulcerative Pathophysiology of Ulcerative ColitisColitis

• The inflammatory process begins at the The inflammatory process begins at the rectosigmoid are of the anal canal and rectosigmoid are of the anal canal and progresses proximal.progresses proximal.

• May progress to involve the entire May progress to involve the entire colon.colon.

• Blood, mucus and pus pool in he lumen Blood, mucus and pus pool in he lumen of the colon (characteristic diarrhea)of the colon (characteristic diarrhea)

• The extent of the colon involving The extent of the colon involving correlates with severity of the disease.correlates with severity of the disease.

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Ulcerative colitisUlcerative colitis

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Ulcerative ColitisUlcerative Colitis:: signs and symptoms signs and symptoms

• Insidious onset• Attacks last 1-3 months• Occur at intervals of months to

years• Diarrhea is the predominant

symptoms of all types of ulcerative colitis.

• Typically 30-40 stools per day, with blood and mucus.

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• When severe disease is present may have other manifestation such as arthritis (related to the inflammatory process going on), uveitis, thromboemboli, fatty liver, cholangitis, and pancreas as well as pericarditis.

• Patients with Ulcerative Colitis have an increased risk of developing colon cancer.

Ulcerative ColitisUlcerative Colitis:: signs and symptoms signs and symptoms

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Complications of Complications of Ulcerative ColitisUlcerative Colitis

• Bowel perforation most deadlyBowel perforation most deadly

• HemorrhageHemorrhage

• Toxic megacolonToxic megacolon

• Increased risk of developing colon cancer. Increased risk of developing colon cancer.

• The risk is higher when there is intensive The risk is higher when there is intensive involvement of the colon with disease for >10 involvement of the colon with disease for >10 years.years.

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Diagnostic of Ulcerative Diagnostic of Ulcerative Colitis Colitis

• Stool for occult bloodStool for occult blood

• Hemoglobin and hematocritHemoglobin and hematocrit

• Colonoscopy**not on active phaseColonoscopy**not on active phase

• Barium enema**”Barium enema**”

• A yearly colonoscopy is strongly recommended A yearly colonoscopy is strongly recommended for anyone who has ulcerative colitis with 8-for anyone who has ulcerative colitis with 8-10years after the DX.10years after the DX.

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Treatment of Ulcerative Treatment of Ulcerative ColitisColitis

• PharmacologicalPharmacological

• Dietary managementDietary management

• Surgical managementSurgical management

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Dietary management in Dietary management in ulcerative colitisulcerative colitis

• No milk productsNo milk products

• No caffeineNo caffeine

• No gas producing or raw fruits & vegetablesNo gas producing or raw fruits & vegetables

• Bulk forming products such as psyllium or Bulk forming products such as psyllium or methylcellulose to decreased diarrhea and methylcellulose to decreased diarrhea and reduce symptoms.reduce symptoms.

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Crohn’s diseaseCrohn’s disease• Primarily affects young people (10-30 years)Primarily affects young people (10-30 years)• Can occur anywhere in the GI tract.Can occur anywhere in the GI tract.• Most frequently affects the terminal ileum and the Most frequently affects the terminal ileum and the

right colonright colon

• Full thickness (transmural) diseaseFull thickness (transmural) disease

• Can lead to ulceration, strictures, fistula Can lead to ulceration, strictures, fistula development.development.

• Skip lesions with areas of the bowel that appear Skip lesions with areas of the bowel that appear normal.normal.

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Pathophysiology of Crohn’s Pathophysiology of Crohn’s diseasedisease

• Begins with an aphthoid lesion Begins with an aphthoid lesion similar to canker sore in the mucosa similar to canker sore in the mucosa and submocosa of the bowel.and submocosa of the bowel.

• Deeper ulcerations, lesions, lumen Deeper ulcerations, lesions, lumen takes on a cobblestone appearance.takes on a cobblestone appearance.

• Fibrotic changes in the bowel cause Fibrotic changes in the bowel cause to thicken and lose of flexibility.to thicken and lose of flexibility.

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Aphtoid lesions of the Aphtoid lesions of the mucosamucosa

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View of the intestine View of the intestine with Crohn’swith Crohn’s

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Late stages of crohn’sLate stages of crohn’s

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Manifestations of Crohn’s Manifestations of Crohn’s diseasedisease• Continuous or episodic diarrheaContinuous or episodic diarrhea

• Stools are liquid or semiformed and Stools are liquid or semiformed and typically typically do not contain blooddo not contain blood..

• Abdominal pain and tenderness are Abdominal pain and tenderness are commoncommon

• A palpable A palpable right lower quadrantright lower quadrant mass mass is often presentis often present

• Fever, malaise, weight loss, fatigue, Fever, malaise, weight loss, fatigue, and anemia are common.and anemia are common.

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• Like ulcerative colitis can have Like ulcerative colitis can have • arthritis, arthritis, • uveitis, uveitis, • thromboembolism, and thromboembolism, and • vascular disorders. vascular disorders. • Also the pt can have cystitis, Also the pt can have cystitis,

renal calculus, and ureteral renal calculus, and ureteral obstruction.obstruction.

Manifestations of Crohn’s Manifestations of Crohn’s diseasedisease

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Complications of Crohn’s Complications of Crohn’s DiseaseDisease

• Intestinal obstructionIntestinal obstruction• AbscessAbscess• FistulaFistula• No associated risk of toxic No associated risk of toxic

megacolon as with ulcerative megacolon as with ulcerative colitis.colitis.

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Gallbladder DisordersGallbladder Disorders

• Gallstones• Cholelithiasis

• Formation• Masses of solid

material (calculi) that form in bile

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Gallstones—Etiology Gallstones—Etiology

• Cholesterol gallstonesCholesterol gallstones• Common in femalesCommon in females• High cholesterol level in bileHigh cholesterol level in bile• Obesity, oral contraceptive, estrogen Obesity, oral contraceptive, estrogen

supplementssupplements

• Bile pigment stonesBile pigment stones• Common in indivCommon in indivudialudial w withith hemolytic hemolytic

anemia, alcoholic cirrhosisanemia, alcoholic cirrhosis

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Gallstones—Pathophysiology Gallstones—Pathophysiology • Vary in shape, size

• Small stones “silent”• Large can obstruct flow of bile

• Initially form in bile ducts, gallbladder, cystic ducts

• May consist primarily of cholesterol (white), bilirubin (black), or both

• Tend to form when bile contains high concentration of component or when bile salts low• Stone grows as more deposits

9494

9595

9696

9797

Gallstones—Signs and Gallstones—Signs and SymptomsSymptoms

• It is fIt is freqrequentlyuently asymptomatic asymptomatic• LLararggee stone stones can causes can cause obstruct obstructionion

ductduct• Sudden severe waves of painSudden severe waves of pain

characterized by characterized by • Upper Upper right right quadquadrantrant

• Radiates to back and Radiates to back and rightright shoulder shoulder

• Pain increase and may decrease if stone Pain increase and may decrease if stone moves onmoves on

• Risk of ruptured gallbladderRisk of ruptured gallbladder• Surgery to remove gallbladder and stoneSurgery to remove gallbladder and stone

9898

Gallstones—Treatment Gallstones—Treatment

• Remove surgicallyRemove surgically• Sometimes stones fragmentSometimes stones fragment• Drugs to break down stoneDrugs to break down stone

9999

HepatitisHepatitis• It is iIt is inflammation of the livernflammation of the liver..• They mThey may result from local infection ay result from local infection

(viral), infection elsewhere (mono) or (viral), infection elsewhere (mono) or from chemfrom chemical andical and//or or drug toxicitydrug toxicity..

• Mild inflammation and necrosisMild inflammation and necrosis• Obstruction of blood and bile flow in liverObstruction of blood and bile flow in liver• Decrease liver cell functionDecrease liver cell function

• Damage to liver cellsDamage to liver cells• The lost of The lost of function of liverfunction of liver• But good functional reserve and excellent But good functional reserve and excellent

regenerationregeneration

100100

Hepatitis virusesHepatitis virusesVirusVirus Other Other

namename FamilyFamily typetype Usual route Usual route

of of transmissiotransmissionn

Hepatitis Hepatitis AA

Infectious Infectious hepatitis hepatitis

PicornavirusPicornavirus RNARNA Oral - fecal Oral - fecal

Hepatitis Hepatitis BB

Serum Serum hepatitis hepatitis

hepadnaviridhepadnaviridae ae

DNADNA Blood or Blood or sexual sexual

Hepatitis Hepatitis cc

Non-A ,Non-Non-A ,Non-B B

flaviviridae flaviviridae RNARNA blood blood

Hepatitis Hepatitis DD

Delta Delta hepatitis hepatitis

Delta viridae Delta viridae RNARNA Blood or Blood or sexual sexual

Hepatitis Hepatitis EE

RNARNA Oral - fecalOral - fecal

Hepatitis Hepatitis FF

Oral - fecalOral - fecal

Hepatitis Hepatitis GG

flaviviridaeflaviviridae bloodblood

101101

Viral Hepatitis—Viral Hepatitis—Pathophysiology Pathophysiology

• Infection from group of viruses that specifically target hepatocytes • HAV, HBV, HCV, HDV, HEV

• Liver cells damaged in 2 ways:• Direct action of virus (HCV)• Cell-mediated immune responses

(HBV)• Cell injury results in:

• Inflammation and necrosis• Swollen hepatocytes and liver.• severe inflammation leads to biliary

stasis•Backup of bile into blood

102102

Viral Hepatitis—Viral Hepatitis—Pathophysiology Pathophysiology

• Hepatic cell necrosis, scarring, Kupffer cell Hepatic cell necrosis, scarring, Kupffer cell hyperplasia, and infiltration by mononuclear hyperplasia, and infiltration by mononuclear phagocytes occur with varying severity.phagocytes occur with varying severity.

• Cellular injury is promoted by cell-mediated Cellular injury is promoted by cell-mediated immune mechanisms (i.e., cytotoxic T cells and immune mechanisms (i.e., cytotoxic T cells and natural killer cells).natural killer cells).

• Regeneration of hepatic cells begins within 48 Regeneration of hepatic cells begins within 48 hours of injury.hours of injury.

• The inflammatory process can damage and The inflammatory process can damage and obstruct bile canaliculi, leading to cholestasis obstruct bile canaliculi, leading to cholestasis and obstructive jaundice.and obstructive jaundice.

• In milder cases the liver parenchyma is not In milder cases the liver parenchyma is not damaged.damaged.

• Damage tends to be most severe in cases of Damage tends to be most severe in cases of HBV and HCV.HBV and HCV.

103103

Viral Hepatitis—Viral Hepatitis—Pathophysiology Pathophysiology

• Chronic inflammation• B, C, D • Persistent inflammation and necrosis

of liver• Eventually causes permanent liver

damage• Carrier state

• B, C, D• Asymptomatic indivudial carries virus

in hepatocytes•Can transmitted

104104

HAV (Infectious Hepatitis) HAV (Infectious Hepatitis)

Small RNA virusSmall RNA virus• Transmitted by oral-fecal routeTransmitted by oral-fecal route

• Contaminated water, shellfishContaminated water, shellfish• Outbreaks in day careOutbreaks in day care• Sexually transmitted Sexually transmitted

• Short incubation period (2-6 weeks)Short incubation period (2-6 weeks)• Causes acute, self-limiting infectionCauses acute, self-limiting infection• No carrier, chronic stateNo carrier, chronic state

105105

HAVHAV• Contagious period (fecal shedding)Contagious period (fecal shedding)

• Begins several weeks before onset of Begins several weeks before onset of symptomssymptoms

• The serumThe serum IgM IgM antibodies –antibodies –HAVHAVconcentration increases initially, concentration increases initially,

• And is followed by an increase of serum And is followed by an increase of serum IgIgG antibodies -HAVG antibodies -HAV.. • IgG antibodies rIgG antibodies remain for years (further emain for years (further

protection)protection)

• VaccineVaccine is necessary is necessary for travel to for travel to endemic areasendemic areas..

• Gamma globulin provides tempGamma globulin provides temporaryorary protection protection

106106

107107

HBV (Serum Hepatitis)HBV (Serum Hepatitis)

• Double stranded DNA virus• 3 antigens

• 2 core antigens•HBcAg, HBeAg

• 1 surface•HBsAg

• e/ antigen stimulates antibody production in body

• Antigens/bodies useful in diagnosing and monitoring

108108

HBVHBV• Carrier state common• Relatively long incubation (2 mo)

• More difficult to tract source of infection• Asymptomatic, can’t be detected, but can be

transmitted• Transmission

• Primarily by infected blood• Transfusions• IV drug users

• Sexual transmission• Woman fetus

• Vaccine for long-term protection• Health-care professionals• Now given to kids

109109

Viral Hepatitis—Etiology: Viral Hepatitis—Etiology: HCV (NANB Hepatitis)HCV (NANB Hepatitis)

• Single strand RNA• Transmission

• Most common through blood transfusion

• half cases enter chronic• Increased risk of hepatocellular

carcinoma• Carrier state

110110

Viral Hepatitis—Etiology: Viral Hepatitis—Etiology: HDV (Delta Virus)HDV (Delta Virus)

• Incomplete RNA virusIncomplete RNA virus• Requires presence of HBsAg to Requires presence of HBsAg to

replicate and produce active replicate and produce active infection infection • Increases severity of HBVIncreases severity of HBV

• TransmissionTransmission• BloodBlood• Increased incidence in IV drug Increased incidence in IV drug

usersusers

111111

Viral Hepatitis—Viral Hepatitis—Etiology: HEVEtiology: HEV

• Single stranded RNA virus• Spread by oral-fecal route• Similar to HAV

• Lacks chronic/carrier state

• Common in Asia and Africa

112112

Viral Hepatitis—Signs and Viral Hepatitis—Signs and SymptomsSymptoms

• Asymptomatic mild fatal• 3 stages

• Precicteric (prodomal)• Icteric (jaundice)• Posticteric (recovery)

113113

114114

115115

Viral Hepatitis—Viral Hepatitis—Treatment Treatment

• No method to destroy virusNo method to destroy virus• Gamma globulin helpful when given Gamma globulin helpful when given

earlyearly• Supportive measuresSupportive measures

• Rest, diet high in protein, carbos, vitRest, diet high in protein, carbos, vit• Chronic B and C treated w/Chronic B and C treated w/

• Interferon alphaInterferon alpha• LamivudineLamivudine• Gradual destruction of liverGradual destruction of liver

• Cirrhosis, hepatocellular cancerCirrhosis, hepatocellular cancer

116116

CirrhosisCirrhosis• Fibrosis Fibrosis

(accumulation of (accumulation of connective tissue) connective tissue) that progresses to that progresses to cirrhosiscirrhosis

• Replacement of liver Replacement of liver tissue by tissue by regenerative nodules regenerative nodules (areas of proliferating (areas of proliferating hepatocytes) hepatocytes) surrounded by surrounded by fibrous scar tissue, fibrous scar tissue, leading to leading to progressive loss of progressive loss of liver functionliver function

• Occurs as a Occurs as a consequence of consequence of chronic liver diseasechronic liver disease

normal

cirrhotic

From: Current Diagnosis & Treatment in Gastroenterology - 2nd Ed. (2003)

117117

Causes of cirrhosis.Causes of cirrhosis.

Autoimmune hepatitisAutoimmune hepatitisAlcohol-induced liver injuryAlcohol-induced liver injuryDrug- or toxin-induced liver injury (ie, Drug- or toxin-induced liver injury (ie, methotrexate)methotrexate)Viral hepatitis B, C, or DViral hepatitis B, C, or DMetabolic diseasesMetabolic diseases    11-Antitrypsin deficiency-Antitrypsin deficiency

 Wilson's disease  Wilson's disease  Hemochromatosis and other copper disorders  Hemochromatosis and other copper disorders  Tyrosinemia  TyrosinemiaNonalcoholic steatohepatitis (NASH) or fatty liverNonalcoholic steatohepatitis (NASH) or fatty liverVascular derangementsVascular derangements  Chronic right heart failure  Chronic right heart failure  Budd-Chiari syndrome  Budd-Chiari syndrome    Long-standing portal vein thrombosisLong-standing portal vein thrombosisBiliary disorders (bile ducts or gallbladder)Biliary disorders (bile ducts or gallbladder)    Primary biliary cirrhosisPrimary biliary cirrhosis  Cystic fibrosis  Cystic fibrosis  Sarcoidosis  Sarcoidosis  Biliary cirrhosis secondary to chronic large bile   Biliary cirrhosis secondary to chronic large bile duct duct obstructionobstruction  Primary sclerosing cholangitis  Primary sclerosing cholangitis  Biliary atresia  Biliary atresia  Congenital paucity of intrahepatic ducts  Congenital paucity of intrahepatic ducts  Progressive familial intrahepatic cholestasis  Progressive familial intrahepatic cholestasisMalnutrition and postjejunoileal bypass surgeryMalnutrition and postjejunoileal bypass surgeryCryptogenic diseaseCryptogenic diseaseFrom: Current Diagnosis & Treatment in Gastroenterology - 2nd Ed. (2003)

Common causes in developed countriesAlcoholismChronic Hepatitis C infection

Asia and AfricaChronic Hepatitis B infection

associated with diabetes, protein malnutrition, obesity, coronary artery disease, and treatment with corticosteroid medications

118118

Morphological classification of Morphological classification of cirhhosiscirhhosis

• Macronoduler cirrhosis (Alcholism, malnutrition)

• Micronoduler cirrhosis (Viral Hepatit)

• Mixt type (most of cirrhosis)

119119

PathophysiologyPathophysiology• Variation from individual to individual in rate of Variation from individual to individual in rate of

progression from fibrosis to cirrhosis, even from progression from fibrosis to cirrhosis, even from the same underlying causethe same underlying cause• Reason unknownReason unknown

Growth regulators = cytokines, epithelial growth factor, hepatocyte growth factor, transforming growth factor-, tumor necrosis factor

** influenced by insulin, glucagon, and patterns of intrahepatic blood flow

injury

hepatocellular hyperplasia

arterial growth(angiogenesis)

regenerativenodules

growthregulators

**

120120

121121

What is NWhat is Non on AAlcoholic lcoholic SSteato teato HHepatisisepatisis????

• A syndrome with liver pathology like alcoholic A syndrome with liver pathology like alcoholic hepatitis, in non-drinkershepatitis, in non-drinkers

• It may progress to cirrhosis,complicated by liver It may progress to cirrhosis,complicated by liver failure or HCCfailure or HCC

• Almost(>98%) association with insulin resistanceAlmost(>98%) association with insulin resistance

• >70 % Family Hx of Type II DM, or IGT>70 % Family Hx of Type II DM, or IGT• Almost(>85%) P’t with Syndrome XAlmost(>85%) P’t with Syndrome X (DM, IGT + Arterial HTN, or TG(DM, IGT + Arterial HTN, or TG, or low HDL, central obesity, , or low HDL, central obesity,

microalbuminemia)microalbuminemia)

• Exclusion of all other causes to steatohepatitisExclusion of all other causes to steatohepatitis

122122

NASH – Risk factorsNASH – Risk factors• DM, type II, family Hx of NIDDM or IGTDM, type II, family Hx of NIDDM or IGT• Obesity Obesity (BMI > 27kg/m(BMI > 27kg/m2 2 in Asian)in Asian)

• Central obesity Central obesity (waist:hip(waist:hip≧≧ 0.85 in 0.85 in♀♀; 0.9 in ; 0.9 in ♂♂ ) )

• Hyperlipidemia; low HDLHyperlipidemia; low HDL• Age: > 45 y/oAge: > 45 y/o• Rapid weight loss Rapid weight loss (Ex: obesity surgery, fasting, (Ex: obesity surgery, fasting,

cachexia)cachexia)

• Co-association with gallstonesCo-association with gallstones

123123

NASH – Suspected NASH – Suspected MechanismMechanism

124124

Cirrhosis of the LiverCirrhosis of the Liver

125125

Due to ↑ estradiol resulting from impaired estrogen metabolism

From: Current Diagnosis & Treatment in Gastroenterology - 2nd Ed. (2003)

Symptoms & Complications

Accumulation of fluid in peritoneal cavity due to hepatic hypertention

Due to portal hypertension

Other non-specific symptomsweakness, fatigue, anorexia, weight loss

speckled mottling of the palm

Umbilical vein opens, blood from portal-venous system gets shunted through here

Portal blood flow through vessels here, likely to bleed

Due to ↓ processing of bilirubin

126126

AscitesAscites, portal , portal hypertensionhypertension

• Portal hypertensionPortal hypertension: Normally, : Normally, blood from the intestines and blood from the intestines and spleen is carried to the liver spleen is carried to the liver through the portal vein. through the portal vein. Disruption of the normal vascular Disruption of the normal vascular architecture by cirrhosis causes architecture by cirrhosis causes blood to back up in the portal blood to back up in the portal circulation leading to circulation leading to hypertension.hypertension.

• Varices:Varices: When blood flow When blood flow through the portal vein slows, through the portal vein slows, blood from the G.I. tract and blood from the G.I. tract and spleen backs up in the vessels of spleen backs up in the vessels of the stomach and esophagus. the stomach and esophagus. These blood vessels may become These blood vessels may become enlarged with very thin walls. enlarged with very thin walls. The enlarged blood vessels may The enlarged blood vessels may burst and cause serious bleeding burst and cause serious bleeding in the upper stomach or in the upper stomach or esophagus that requires esophagus that requires immediate medical attention.immediate medical attention.

127127

Mechanisms of Ascites in Mechanisms of Ascites in CirrhosisCirrhosis

128128

Micronodular CirrhosisMicronodular Cirrhosis

• Micronodular cirrhosis. Ongoing liver damage Micronodular cirrhosis. Ongoing liver damage associated with necrosis and regeneration associated with necrosis and regeneration results in altered structure of liver that is results in altered structure of liver that is nodular and firm.. Nodules are less than 3 mm nodular and firm.. Nodules are less than 3 mm in diameter, hence micronodular.in diameter, hence micronodular.

• Note the yellow change due to fatty deposits Note the yellow change due to fatty deposits (common in alcolohic cirrosis). Micronodular (common in alcolohic cirrosis). Micronodular cirrhosis is also seen with Wilson’disease, cirrhosis is also seen with Wilson’disease, primary biliary cirrhosis, and hemochromatosis. primary biliary cirrhosis, and hemochromatosis.

Normal LiverNormal Liver

129129

Complications of CirrhosisComplications of Cirrhosis

• Portal hypertension with portal to systemic shunting

• Loss of hepatocytes

• Other complications

130130

Main consequences of hepatic Main consequences of hepatic hypertensionhypertension

1.1. Ascites = accumulation of fluid in intraperitoneal cavityAscites = accumulation of fluid in intraperitoneal cavity

2.2. Formation of porto-systemic shunts Formation of porto-systemic shunts leads toleads to new blood new blood vessels channel blood from intestines to heart instead of vessels channel blood from intestines to heart instead of first passing through liver. first passing through liver.

• ExExaminationamination: esophageal varices, caput medusae.: esophageal varices, caput medusae.• Esophageal varices are most dangerous because they often Esophageal varices are most dangerous because they often

rupture.rupture.

3.3. Congestive splenomegaly = enlargement of the spleenCongestive splenomegaly = enlargement of the spleen

4.4. Hepatic encephalopathy Hepatic encephalopathy is characterized byis characterized by swelling of swelling of the brain caused by accumulation of toxic substances in the brain caused by accumulation of toxic substances in the blood (esp. ammonia) due to porto-systemic shunts the blood (esp. ammonia) due to porto-systemic shunts (blood bypasses cleaning by the liver) and decreased (blood bypasses cleaning by the liver) and decreased liver functionliver function

• Signs can include impaired cognition, decreased level of Signs can include impaired cognition, decreased level of consciousness, and comaconsciousness, and coma

131131

DiagnosisDiagnosis

• Displaying signs of portal Displaying signs of portal hypertensionhypertension

• Liver function testsLiver function tests• If clinical data and lab tests suggest If clinical data and lab tests suggest

cirrhosis, confirm by liver biopsycirrhosis, confirm by liver biopsy..

132132

TreatmentsTreatments

• Eliminating injurious drugs, such as Eliminating injurious drugs, such as alcohol and hepatotoxic drugsalcohol and hepatotoxic drugs

• Reducing intake of drugs metabolized Reducing intake of drugs metabolized by the liverby the liver

• Providing adequate nutritionProviding adequate nutrition• Therapy for patients with varicesTherapy for patients with varices• Treatments to slow fibrosisTreatments to slow fibrosis• End stage disease requires liver End stage disease requires liver

transplanttransplant

133133

AcuteAcute Pancreatitis Pancreatitis

134134

PancreasPancreas• Complicated Complicated

exocrine and exocrine and endocrine gland endocrine gland located in the upper located in the upper abdominal regionabdominal region

• Non-capsulated Non-capsulated lobular organ about lobular organ about 12 to 20 cm long 12 to 20 cm long and lies behind the and lies behind the peritoneum of the peritoneum of the posterior abdominal posterior abdominal wallwall,,

• Divided into head, Divided into head, body, and tailbody, and tail

135135

PancreasPancreas• TailTail

• Adjacent to hilum of spleenAdjacent to hilum of spleen• BodyBody

• Extends horizontally behind Extends horizontally behind stomachstomach

• HeadHead• Nestled in the duodenal Nestled in the duodenal

sweepsweep• Sphincter of OddiSphincter of Oddi

• Circular smooth muscle that Circular smooth muscle that surrounds both the common surrounds both the common bile duct and the main bile duct and the main pancreatic ductpancreatic duct

• Ampule of VaterAmpule of Vater• Site where the common bile Site where the common bile

duct and main pancreatic duct and main pancreatic duct drain into duodenumduct drain into duodenum

136136

137137

PancreasPancreas• The lobes of the pancreas are divided The lobes of the pancreas are divided

into subunits of acini cells and the into subunits of acini cells and the Islets of LangerhansIslets of Langerhans• Acini cells are involved in the production Acini cells are involved in the production

of 20 different digestive enzymes and of 20 different digestive enzymes and include amylase released to digest include amylase released to digest starch and lipase released to digest fatsstarch and lipase released to digest fats

• The most abundant of the enzymes is The most abundant of the enzymes is trypsin, which is released into the trypsin, which is released into the duodenumduodenum

• These enzymes are activated by These enzymes are activated by enterokinase, which is produced by the enterokinase, which is produced by the intestinal mucosaintestinal mucosa

138138

PathophysiologyPathophysiology• Triggering mechanism not exactly Triggering mechanism not exactly

understoodunderstood..• Pancreatic enzymes that escape Pancreatic enzymes that escape

into the surrounding tissue due to into the surrounding tissue due to compromised pancreatic function compromised pancreatic function seem to be the primary causeseem to be the primary cause..

• When the pancreas becomes When the pancreas becomes damaged or the ducts become damaged or the ducts become blocked, the trypsin inhibitor blocked, the trypsin inhibitor accumulates and activates the accumulates and activates the pancreatic secretions that escape pancreatic secretions that escape into the surrounding tissue, into the surrounding tissue, resulting in inflammation, thereby resulting in inflammation, thereby causing acute pancreatitiscausing acute pancreatitis

139139

PathophysiologyPathophysiology• Release of kallikrein and chymotrypsin results Release of kallikrein and chymotrypsin results

in increased capillary membrane permeability, in increased capillary membrane permeability, leading to leakage of fluid into the interstitium leading to leakage of fluid into the interstitium and development of edema and relative and development of edema and relative hypovolemiahypovolemia

• Elastase is the most harmful in terms of direct Elastase is the most harmful in terms of direct cell damage, it causes dissolution of the elastic cell damage, it causes dissolution of the elastic fibers of blood vessels and cuts, leading to fibers of blood vessels and cuts, leading to hemorrhagehemorrhage

• Phospholipase A in the presence of bile, Phospholipase A in the presence of bile, destroys phosholipids of cell membranes destroys phosholipids of cell membranes causing severe pancreatic and adipose tissue causing severe pancreatic and adipose tissue necrosisnecrosis

• Lipase flows into damaged tissue and is Lipase flows into damaged tissue and is absorbed into systemic circulation, resulting in absorbed into systemic circulation, resulting in fat necrosis of the pancreas and surrounding fat necrosis of the pancreas and surrounding tissuestissues

140140

Acute PancreatitisAcute Pancreatitis

• Sudden onset of unrelenting upper Sudden onset of unrelenting upper abdominal pain resulting from abdominal pain resulting from inflammation of the pancreasinflammation of the pancreas

• Patients commonly present severe Patients commonly present severe abdominal painabdominal pain

• Requires admission to the hospital for Requires admission to the hospital for medical management, accounting for medical management, accounting for between 166,000 to 224,000 between 166,000 to 224,000 admissions each year with an estimated admissions each year with an estimated annual cost of $3.6 to $6 billionannual cost of $3.6 to $6 billion

141141

Acute PancreatitisAcute Pancreatitis• Inflammation of the Inflammation of the

pancreas that pancreas that produces exocrine produces exocrine and endocrine and endocrine dysfunction dysfunction

• Results from Results from premature activation premature activation of pancreatic of pancreatic exocrine enzymes exocrine enzymes (trypsin, (trypsin, phospholipase A, and phospholipase A, and elastase)elastase)

142142

Acute PancreatitisAcute Pancreatitis

Fig. 42-13

143143

Causes of Acute Causes of Acute PancreatitisPancreatitis• Ethanol abuse

• Biliary diseases• Gallstones• Choledocholithiasis• Biliary sludge• Microlithiasis

• Mechanical/structural injury• Sphincter of Oddi

dysfunction• Pancreas divisum• Trauma• Postendoscopic

retrograde cholangiopancreatography

• Pancreatic malignancy• Peptic Ulcer Disease• IBD

• Medications• Azathiprine/6-

mercaptopurine• Dideoxyinosine• Pentamidine• Sulfonamides• Thiazide diuretics• ACEI

• Metabolic• Hypertriglyceridemia• Hypercalcemia

• Infectious• Viral• Bacterial• Parasitic

• Vascular• Vasculitis

• Genetic predisposition• idiopathic

144144

Acute Pancreatitis: Damage Acute Pancreatitis: Damage and Destructionand Destruction

• Inflammation is caused by Inflammation is caused by premature activation of premature activation of enzymes which leads to enzymes which leads to tissue damagetissue damage

• If pancreatitis damages the If pancreatitis damages the islets of Langerhans, diabetes islets of Langerhans, diabetes mellitus may resultmellitus may result

• Severe sudden pancreatitis Severe sudden pancreatitis causes massive hemorrhage causes massive hemorrhage and total destruction of the and total destruction of the pancreas, manifested as pancreas, manifested as diabetic acidosis, shock and diabetic acidosis, shock and comacoma

145145

Clinical PresentationClinical Presentation• Upper abdominal pain rapidly Upper abdominal pain rapidly

increasing in severity, often within 60 increasing in severity, often within 60 minutesminutes

• Epigastric painEpigastric pain• Right-sided painRight-sided pain• Diffuse abdominal pain with radiation Diffuse abdominal pain with radiation

to backto back• Pain rarely only in left upper quadrantPain rarely only in left upper quadrant• RestlessRestless• Prefer to sit and leanPrefer to sit and lean• FeverFever• TachycardiaTachycardia

146146

Abdominal ExaminationAbdominal Examination• Decreased or absent bowel Decreased or absent bowel

soundssounds• Abdominal tendernessAbdominal tenderness• GuardingGuarding• Palpable mass in epigastric areaPalpable mass in epigastric area• Biliary colic Biliary colic • Jaundice if there’s obstruction Jaundice if there’s obstruction

of the bile ductof the bile duct• Cullen’s signCullen’s sign• Grey Turner’s SignGrey Turner’s Sign

147147

Clinical ManifestationsClinical Manifestations• Abdominal distentionAbdominal distention• Abdominal guardingAbdominal guarding• Abdominal tympanyAbdominal tympany• Hypoactive bowel soundsHypoactive bowel sounds• Severe disease: Severe disease:

peritoneal signs, ascites, peritoneal signs, ascites, jaundice, palpable jaundice, palpable abdominal mass, Grey abdominal mass, Grey Turner’s sign, Cullen’s Turner’s sign, Cullen’s sign, and signs of sign, and signs of hypovolemic shockhypovolemic shock

148148

What testing will What testing will reveal……reveal……

• Serum amylase and lipase levels Serum amylase and lipase levels elevated 3-5 times normalelevated 3-5 times normal

• Urine amylase increased for 1-2 weeksUrine amylase increased for 1-2 weeks• Elevated WBCElevated WBC• Decreased serum calciumDecreased serum calcium• Elevated serum bilirubin, AST, ALT, LD, Elevated serum bilirubin, AST, ALT, LD,

and alkaline phosphataseand alkaline phosphatase• Abdominal XRAYS and CT’s showing Abdominal XRAYS and CT’s showing

pleural effusions and bowel dilation pleural effusions and bowel dilation and ileusand ileus

• Serum triglycerides >150mg/dlSerum triglycerides >150mg/dl

149149

Ranson’s CriteriaRanson’s Criteria

• The severity of acute pancreatitis is The severity of acute pancreatitis is determined by the existence of certain determined by the existence of certain criteria, called Ranson’s criteriacriteria, called Ranson’s criteria

• The more criteria met by the patient, the The more criteria met by the patient, the more severe the episode of pancreatitismore severe the episode of pancreatitis

• 1% mortality: fewer than three1% mortality: fewer than three• 16%: three or four criteria16%: three or four criteria• 40% with five or six criteria40% with five or six criteria• 100%: seven or eight criteria100%: seven or eight criteria

150150

Ranson’s CriteriaRanson’s Criteria

• On admissionOn admission• Patient older than 55Patient older than 55• WBC > 16,000WBC > 16,000• Serum glucose >200Serum glucose >200• Serum lactate dehydrogenase >350Serum lactate dehydrogenase >350• Aspartate aminotransferase > 250Aspartate aminotransferase > 250

• During initial 48 hours after admissionDuring initial 48 hours after admission• 10% decrease in Hct10% decrease in Hct• BUN increase > 5BUN increase > 5• Serum calcium < 8Serum calcium < 8• Base deficit > 4Base deficit > 4• PaO2 < 60PaO2 < 60• Estimated fluid sequestration > 6 litersEstimated fluid sequestration > 6 liters

151151

Common Complications of Common Complications of Acute PancreatitisAcute Pancreatitis• Pulmonary

• Atelactasis• Pleural effusions• ARDS

• Cardiovascular• Cardiogenic shock

• Neurologic• Pancreatic encephalopathy

• Metabolic• Metabolic acidosis• Hypocalcemia• Altered glucose metabolism

• Hematologic• DIC• GI bleeding

• Renal• Prerenal failure

152152

ManagementManagement• Fluid ManagementFluid Management• Nutritional supportNutritional support

• Rest gutRest gut• TPNTPN

• Pain managementPain management• Supporting other organ systemsIV replacement of Supporting other organ systemsIV replacement of

fluids, proteins, and electrolytesfluids, proteins, and electrolytes• Fluid volume replacement and blood transfusionsFluid volume replacement and blood transfusions• Withholding food and fluids to rest the pancreasWithholding food and fluids to rest the pancreas• NG tube suctioningNG tube suctioning• DrugsDrugs• Peritoneal lavagePeritoneal lavage• Surgical drainageSurgical drainage• Laparotomy to remove obstructionLaparotomy to remove obstruction

153153

Chronic PancreatitisChronic Pancreatitis

• Defined as chronic inflammatory Defined as chronic inflammatory condition that causes irreversible condition that causes irreversible damage to pancreatic structure damage to pancreatic structure and functionand function

• Causes: ETOH abuse, malnutrition, Causes: ETOH abuse, malnutrition, hyperPTH, pancreas divisum, hyperPTH, pancreas divisum, ampullary stenosis, cystic fibrosis, ampullary stenosis, cystic fibrosis, hereditary, trauma, idiopathichereditary, trauma, idiopathic

154154

Chronic PancreatitisChronic Pancreatitis

• Chronic pancreatitis results in Chronic pancreatitis results in interstitial inflammation winterstitial inflammation with ith duct duct obstruction and dilation leading to obstruction and dilation leading to parenchymal loss and fibrosis.parenchymal loss and fibrosis.

• Loss of both exocrine and Loss of both exocrine and endocrineendocrine functions. functions.

• Clinicically significant Clinicically significant malabsorption occurs when 90% of malabsorption occurs when 90% of pancreas is lost.pancreas is lost.

155155

Chronic PancreatitisChronic Pancreatitis• Presents as midepigastric Presents as midepigastric

abdominal pain, nausea, vomitingabdominal pain, nausea, vomiting..• PPaattientientss m may appear chronically ay appear chronically

ill, will, with ith sign of pancreatic sign of pancreatic insufficiency such as weight loss, insufficiency such as weight loss, steatorrhea, clubbing, polyuriasteatorrhea, clubbing, polyuria

156156

Chronic PancreatitisChronic Pancreatitis

• Amylase and lipase may be normal if Amylase and lipase may be normal if pancreas is fibroticpancreas is fibrotic

• CT scan may help ID pseudocyst or CT scan may help ID pseudocyst or abscessabscess

• Tx: IVF’s anti-emetics, narcoticsTx: IVF’s anti-emetics, narcotics• Pancreatic extracts to improve Pancreatic extracts to improve

absorption and painabsorption and pain• If pain is increasing or intractable, image If pain is increasing or intractable, image

pancreas to look for complicationspancreas to look for complications