dr. Rena Normasari**

dr rena normasari

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dr rena normasari

small (usually

caused by herpes simplex virus (HSV) type 1.transmitted from person to personIn most adults the primary infection is asymptomaticsolitary or multiple small (

Pseudomembranous candidiasis (thrush, moniliasis) is the most common fungal infection of the oral cavitycommon among persons rendered vulnerable by diabetes mellitus, anemia, antibiotic or glucocorticoid therapy, immunodeficiency, or debilitating illnesses such as disseminated cancer. **

a whitish, well-defined mucosal patch or plaque caused by epidermal thickening or hyperkeratosis. human papillomavirus antigen has been identified in some tobacco-related lesions, raising the possibility that the virus and tobacco act in concert in the induction of these lesions.undergo transformation to squamous cell carcinoma**

refers to red, velvety, often granular, circumscribed areas that may or may not be elevated, having poorly defined, irregular boundaries.almost invariably reveals marked epithelial dysplasia (the malignant transformation rate is >50%)**

Sialadenitis : inflammation caused by infection (e.g. mumps, various bacteria) or autoimmune reaction (as in Sjgren syndrome).Pleomorphic adenoma (mixed salivary gland tumor): slow growing locally infiltrative tumor composed of heterogeneous epithelial elements and an often myxoid stroma.Warthin tumor: benign tumor composed of epithelial cells and dense lymphoid tissue.**

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dr rena normasari

(1) aperistalsis, (2) partial or incomplete relaxation of the lower esophageal sphincter with swallowing, and (3) increased resting tone of the lower esophageal sphincter. loss of intrinsic inhibitory innervation of the lower esophageal sphincter and smooth muscle segment of the esophageal body. progressive dysphagia and inability to completely convey food to the stomach**

In hiatal hernia, dilated segment of the stomach to protrude above the diaphragm. In paraesophageal hernias, a separate portion of the stomach, usually along the greater curvature, enters the thorax through the widened foramen.suffer from heartburn or regurgitationParaesophageal hernias can become strangulated or obstructed.**

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Longitudinal tears in the esophagus at the esophagogastric junction inadequate relaxation of the musculature of the lower esophageal sphincter during vomitingupper gastrointestinal bleeding episodessupportive therapy with vasoconstrictive medications, transfusions, and sometimes balloon tamponade**

Esophageal laceration (Mallory-Weiss tears)**

When portal venous blood flow into the liver is impeded by cirrhosis or other causes, the resultant portal hypertension induces the formation of collateral bypass channelsThe increased pressure in the esophageal plexus produces dilated tortuous vessels called varices. **

Figure 17-4 Esophageal varices. A, A view of the everted esophagus and gastroesophageal junction, showing dilated submucosal veins (varices). The blue-colored varices have collapsed in this postmortem specimen. B, Low-power cross-section of a dilated submucosal varix that has ruptured through the mucosa. A small amount of thrombus is present within the point of rupture. C, Hepatic venogram after injection of dye into portal veins (PV) to show a large tortuous gastroesophageal varix (arrow) extending superiorly from the patent main portal vein. (C, courtesy of Dr. Emily Sedgwick, Brigham and Women's Hospital, Boston, MA.)Downloaded from: StudentConsult (on 24 February 2010 11:37 PM) 2005 Elsevier **

dr rena normasari

Injury to the esophageal mucosa with subsequent inflammationprolonged gastric intubation, uremia, ingestion of corrosive or irritant substances, and radiation or chemotherapyThe dominant manifestation of reflux disease is heartburn, sometimes accompanied by regurgitation of a sour brash. **

Figure 17-5 Reflux esophagitis. Low-power view of the superficial portion of the mucosa. Numerous eosinophils within the squamous epithelium, elongation of the lamina propria papillae, and basal zone hyperplasia are present.Downloaded from: StudentConsult (on 24 February 2010 11:37 PM) 2005 Elsevier **

dr rena normasari

replacement of the normal distal stratified squamous mucosa by metaplastic columnar epithelium containing goblet cells.a complication of long-standing gastroesophageal refluxrisk for the development of adenocarcinoma**

Figure 17-6 Barrett esophagus. A, B, Gross view of distal esophagus (top) and proximal stomach (bottom), showing A, the normal gastroesophageal junction (arrow) and B, the granular zone of Barrett esophagus (arrow). C, Endoscopic view of Barrett esophagus showing red velvety gastrointestinal mucosa extending from the gastroesophageal orifice. Note the paler squamous esophageal mucosa.Downloaded from: StudentConsult (on 24 February 2010 11:37 PM) 2005 Elsevier **

dr rena normasari

Figure 17-7 Barrett esophagus. Microscopic view showing squamous mucosa and intestinal-type columnar epithelial cells (goblet cells) in a glandular mucosa.Downloaded from: StudentConsult (on 24 February 2010 11:37 PM) 2005 Elsevier **

dr rena normasari

insidious in onset and produces dysphagia and obstruction gradually and late.Squamous cell carcinomas arise from dysplastic epithelium, associated with esophagitis, smoking; may be locally invasive.Adenocarcinomas arise usually in Barrett esophagus

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Figure 17-8 Large ulcerated squamous cell carcinoma of the esophagus.Downloaded from: StudentConsult (on 24 February 2010 11:37 PM) 2005 Elsevier **

dr rena normasari

Figure 17-9 Squamous cell carcinoma of the esophagus: low-power microscopic view showing invasion into the submucosa.Downloaded from: StudentConsult (on 24 February 2010 11:37 PM) 2005 Elsevier **

dr rena normasari

Figure 17-10 Transition from Barrett esophagus to adenocarcinoma.Downloaded from: StudentConsult (on 24 February 2010 11:37 PM) 2005 Elsevier **

dr rena normasari

Figure 17-11 Adenocarcinoma of the esophagus. A, Gross view of an ulcerated, exophytic mass at the gastroesophageal junction, arising from the granular mucosa of Barrett esophagus. The gray-white esophageal mucosa is on the top, and the folds of gastric mucosa are below. (A, courtesy of Dr. James Gulizia, Brigham and Women's Hospital, Boston, MA.) B, Microscopic view of malignant intestinal-type glands in adenocarcinoma arising from Barrett esophagus.Downloaded from: StudentConsult (on 24 February 2010 11:37 PM) 2005 Elsevier **

dr rena normasari

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dr rena normasari

use of NSAIDs, excessive alcohol consumption, heavy smoking,chemotherapeutic drugssuperficial inflammation to involvement of the entire mucosal thickness with hemorrhage and focal erosions.

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Figure 17-13 Acute gastritis. A, Gross view showing punctate erosions in an otherwise unremarkable mucosa; adherent blood is dark due to exposure to gastric acid. B, Low-power microscopic view of focal mucosal disruption with hemorrhage; the adjacent mucosa is normal.Downloaded from: StudentConsult (on 24 February 2010 11:37 PM) 2005 Elsevier **

dr rena normasari

chronic infection by the bacillus H. pyloricombined influence of bacterial enzymes and toxins and release of noxious chemicals by the recruited neutrophils.mononuclear cell infiltration in the lamina propria with intestinal metaplasialong-term risk of gastric carcinoma for persons with H. pylori-associated chronic gastritis is increased**

Figure 17-14 Chronic gastritis, showing partial replacement of the gastric mucosal epithelium by intestinal metaplasia (upper left) and inflammation of the lamina propria (right) containing lymphocytes and plasma cells.Downloaded from: StudentConsult (on 24 February 2010 11:37 PM) 2005 Elsevier **

dr rena normasari

(1) H. pylori infection, which has a strong causal relationship with peptic ulcer development, and (2) mucosal exposure to gastric acid and pepsinepigastric pain, often described as gnawing, burning, or boringdamages epithelial cells; typically, sharply demarcated mucosal defects with underlying necrosis**

Figure 17-17 Diagram of causes of, and defense mechanisms against, peptic ulceration. Diagram of the base of a nonperforated peptic ulcer, demonstrating the layers of necrosis (N), inflammation (I), granulation tissue (G), and scar (S), moving from the luminal surface at the top to the muscle wall at the bottom.Downloaded from: StudentConsult (on 24 February 2010 11:37 PM) 2005 Elsevier **

dr rena normasari

Figure 17-18 Peptic ulcer of the duodenum. Note that the ulcer is small (2 cm) with a sharply punched-out appearance. Unlike cancerous ulcers, the margins are not elevated. The ulcer base is clean. (Courtesy of Robin Foss, University of Florida, Gainesville, FL.)Downloaded from: StudentConsult (on 24 February 2010 11:37 PM) 2005 Elsevier **

dr rena normasari

Focal, acutely developing gastric mucosal defects that may appear after severe physiologic stress are called stress ulcers.severe trauma, burns, CNS trauma or hemorrhageusually small, multiple, hemorrhagic ulcers that are often shallow.

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Figure 17-19 Multiple stress ulcers of the stomach, highlighted by dark digested blood on their surfaces.Downloaded from: StudentConsult (on 24 February 2010 11:37 PM) 2005 Elsevier **

dr rena normasari

nodule or mass that projects above the level of the surrounding mucosa. (1) hyperplastic polyps (80% to 85%), (2) fundic gland polyps (10%), and (3) adenomatous polyps (5%). **

Asymptomatic,abdominal discomfort or weight lossIntestinal-Type Adenocarcinoma. The risk is particularly high in individuals with chronic gastritis Gastritis is generally accompanied by severe gastric atrophy and intestinal metaplasia, which are ultimately followed by dysplasia and cancer. Chronic inflammation induced by H. pylori may release reactive oxygen species, which eventually cause DNA damage**

Diffuse AdenocarcinomaMutations in E-cadherincomposed of gastric type of mucous cells (signet ring cells) that permeate the mucosa without forming glands**

Figure 17-25 Diagram of growth patterns and spread of gastric carcinoma. In early gastric carcinoma (A), the tumor is confined to the mucosa and submucosa and may exhibit an exophytic, flat or depressed, or excavated conformation. Advanced gastric carcinoma (B) extends into the muscularis propria and beyond. Linitis plastica is an extreme form of flat or depressed advanced gastric carcinoma.Downloaded from: StudentConsult (on 24 February 2010 11:37 PM) 2005 Elsevier **

dr rena normasari

Figure 17-25 Diagram of growth patterns and spread of gastric carcinoma. In early gastric carcinoma (A), the tumor is confined to the mucosa and submucosa and may exhibit an exophytic, flat or depressed, or excavated conformation. Advanced gastric carcinoma (B) extends into the muscularis propria and beyond. Linitis plastica is an extreme form of flat or depressed advanced gastric carcinoma.Downloaded from: StudentConsult (on 24 February 2010 11:37 PM) 2005 Elsevier **

dr rena normasari

Figure 17-26 Gastric carcinoma. Gross photograph showing an ill-defined, excavated central ulcer surrounded by irregular, heaped-up borders.Downloaded from: StudentConsult (on 24 February 2010 11:37 PM) 2005 Elsevier **

dr rena normasari

Figure 17-27 Gastric carcinoma. A, Intestinal type demonstrating gland formation by malignant cells, which are invading the muscular wall of the stomach. B, Diffuse type demonstrating signet-ring carcinoma cells.Downloaded from: StudentConsult (on 24 February 2010 11:37 PM) 2005 Elsevier **

dr rena normasari

Figure 17-27 Gastric carcinoma. A, Intestinal type demonstrating gland formation by malignant cells, which are invading the muscular wall of the stomach. B, Diffuse type demonstrating signet-ring carcinoma cells.Downloaded from: StudentConsult (on 24 February 2010 11:37 PM) 2005 Elsevier **

dr rena normasari

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dr rena normasari

congenital and as an acquired disorder. an aganglionic segment is formed that lacks both the Meissner submucosal and Auerbach myenteric plexuses. In most cases a delay occurs in the initial passage of meconium, which is followed by vomiting in 48 to 72 hours. **

Ischemic lesions may be restricted to the small or large intestine or may affect both, depending on the particular vessel or vessels involved. sudden onset of abdominal pain, sometimes accompanied by bloody diarrhea.Arterial thrombosis, Arterial embolism, Venous thrombosis, Nonocclusive ischemia, radiation injury, volvulus, stricture, and internal or external herniation

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Figure 17-48 Acute ischemic bowel disease. Schematic of the three levels of severity, diagrammed for the small intestine.Downloaded from: StudentConsult (on 24 February 2010 11:38 PM) 2005 Elsevier **

dr rena normasari

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dr rena normasari

Tortuous dilations of submucosal and mucosal blood vessels often in the cecum or right colon, usually only after the sixth decade of life. **

variceal dilations of the anal and perianal submucosal venous plexuseselevated venous pressure within the hemorrhoidal plexus. chronic constipation and the venous stasis of pregnancy in younger women, portal hypertension,Varicosities in the superior and middle hemorrhoidal veins appear above the anorectal line and are covered by rectal mucosa (internal hemorrhoids). Those that appear below the anorectal line represent dilations of the inferior hemorrhoidal plexus and are covered by anal mucosa (external hemorrhoids). **

a blind pouch that communicates with the lumen of the gut.(1) exaggerated peristaltic contractions with abnormal elevation of intraluminal pressure and (2) focal defects peculiar to the normal muscular colonic wall.Asymptomatic A high-fiber diet is recommended on the theory that the increased stool bulk reduces the exaggerated peristalsis. **

Hernias, a weakness or defect in the wall of the peritoneal cavity, may permit protrusion of a pouchlike, serosa-lined sac of peritoneumIntussusception denotes telescoping of a proximal segment of bowel into the immediately distal segment. Volvulus refers to twisting of a loop of bowel or other structure about its base of attachment**

Figure 17-53 Schematic depicting the four major causes of intestinal obstruction: (1) Herniation of a segment in the umbilical or inguinal regions; (2) adhesion between loops of intestine; (3) intussusception; (4) volvulus formation.Downloaded from: StudentConsult (on 24 February 2010 11:38 PM) 2005 Elsevier **

dr rena normasari

The major types of diarrheal diseases are: secretory, osmotic, exudative, malabsorption-related, and due to deranged motility.Secretory diarrhea can be caused by viruses or enterotoxin-producing bacteria such as E. coliThe most common agents of enterocolitis among protozoa are Entamoeba histolytica, Giradia lamblia and Cryptosporidium parvum.

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Secretory DiarrheaInfectious: viral damage to surface epitheliumRotavirusNorwalk virusEnteric adenovirusesInfectious: enterotoxin-mediatedVibrio choleraeEscherichia coliBacillus cereusClostridium perfringensNeoplastic: tumor elaboration of peptides or serotoninExcessive laxative use

Osmotic DiarrheaLactulose therapy (for hepatic encephalopathy, constipation)Prescribed gut lavage for diagnostic proceduresAntacids (MgSO4 and other magnesium salts)Exudative DiseasesInfectious: destruction of the epithelial layerShigella spp.Salmonella spp.Campylobacter spp.Entamoeba histolyticaIdiopathic inflammatory bowel disease

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MalabsorptionDefective intraluminal digestionDefective mucosal-cell absorptionReduced small intestinal surface areaLymphatic obstructionInfectious: impaired mucosal-cell absorptionGiardia lamblia

Deranged MotilityDecreased intestinal retention timeSurgical reduction of gut lengthNeural dysfunction, including irritable bowel syndromeHyperthyroidismDecreased motility (increased intestinal retention time)Surgical creation of a "blind" intestinal loopBacterial overgrowth in the small intestine

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OrganismPathogenic MechanismSourceClinical FeaturesEscherichia coliETECCholera-like toxin, no invasionFood, waterTraveler's diarrhea, including watery diarrheaSTECShiga toxin, no invasionUndercooked beef productsHemorrhagic colitis, hemolyticuremic syndrome EPECAttachment, enterocyte effacement, no invasionWeaning foods, waterWatery diarrhea, infants and toddlersEIECInvasion, local spreadCheese, water, person to personFever, pain, diarrhea, dysentery

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OrganismPathogenic MechanismSourceClinical FeaturesSalmonella spp.Invasion, translocation, lymphoid inflammation, disseminationMilk, beef, eggs, poultryFever, pain, diarrhea or dysentery, bacteremia, extra-intestinal infection, common source of outbreaksShigella spp.Invasion, local spreadPerson to person, low inoculumFever, pain, diarrhea, dysentery, epidemic spreadCampylobacter?Toxins, invasionMilk, poultry, animal contactFever, pain, diarrhea, dysentery, food sources, animal reservoirsYersinia enterocoliticaInvasion, translocation, lymphoid inflammation, disseminationMilk, porkFever, pain, diarrhea, mesenteric lymphadenitis, extra-intestinal infection, food sources

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OrganismPathogenic MechanismSourceClinical FeaturesVibrio cholerae, other Vibrio spp.Enterotoxin, no invasionWater, shellfish, person to personWatery diarrhea, cholera, pandemic spreadClostridium difficileCytotoxin, local invasionNosocomial environmental spreadFever, pain, bloody diarrhea, after antibiotic use, nosocomial acquisitionClostridium perfringensEnterotoxin, no invasionMeat, poultry, fishWatery diarrhea, food sources, "pigbel"Mycobacterium tuberculosisInvasion, mural inflammatory foci with necrosis and scarringContaminated milk, swallowing of coughed-up organismsChronic abdominal pain, complications of malabsorption, stricture, perforation, fistulas, hemorrhage

most commonly located at the terminal ileum.characterized by: Sharply limited transmural involvement of the bowel by an inflammatory process with mucosal damage, Presence of noncaseating granulomas, Fistula formation diarrhea, crampy abdominal pain, and fever lasting days to weeks.

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Figure 17-40 Crohn disease of ileum, showing narrowing of the lumen, bowel wall thickening, serosal extension of mesenteric fat ("creeping fat"), and linear ulceration of the mucosal surface (arrowheads).Downloaded from: StudentConsult (on 24 February 2010 11:38 PM) 2005 Elsevier **

dr rena normasari

Figure 17-41 Crohn disease of the colon; a deep fissure extending into the muscle wall, a second, shallow ulcer (on the upper right), and relative preservation of the intervening mucosa. Abundant lymphocyte aggregates are present, evident as dense blue patches of cells at the interface between mucosa and submucosa.Downloaded from: StudentConsult (on 24 February 2010 11:38 PM) 2005 Elsevier **

dr rena normasari

Figure 17-42 Crohn disease of the colon. A noncaseating granuloma is present in the lamina propria of an uninvolved region of colonic mucosa (arrow).Downloaded from: StudentConsult (on 24 February 2010 11:38 PM) 2005 Elsevier **

dr rena normasari

an ulceroinflammatory disease affecting the colon, which is limited to the mucosa and submucosaIn ulcerative colitis: Well-formed granulomas are absent.There are no skip lesions.The mucosal ulcers rarely extend below the submucosa, and there is surprisingly little fibrosis.Mural thickening does not occur, and the serosal surface is usually completely normal.There appears to be a high risk of carcinoma development. bloody mucoid diarrhea that may persist for days, weeks, or months

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Figure 17-43 Comparison of the distribution patterns of Crohn disease and ulcerative colitis, as well as the different conformations of the ulcers and wall thickenings.Downloaded from: StudentConsult (on 24 February 2010 11:38 PM) 2005 Elsevier **

dr rena normasari

Figure 17-44 Ulcerative colitis. Ulcerated hemorrhagic surface with knobby pseudopolyps. (Courtesy of Dr. Kim Bechard, Brigham and Women's Hospital, Boston, MA.)Downloaded from: StudentConsult (on 24 February 2010 11:38 PM) 2005 Elsevier **

dr rena normasari

Figure 17-45 Ulcerative colitis. Low-power micrograph showing marked chronic inflammation of the mucosa with atrophy of colonic glands, moderate submucosal fibrosis, and a normal muscle wall.Downloaded from: StudentConsult (on 24 February 2010 11:38 PM) 2005 Elsevier **

dr rena normasari

(1) a low content of unabsorbable vegetable fiber, (2) a corresponding high content of refined carbohydrates, (3) a high fat content (as from meat), and (4) decreased intake of protective micronutrientsCecal and right colonic cancers most often are called to clinical attention by the appearance of fatigue, weakness, and iron deficiency anemia. Left-sided lesions may produce occult bleeding, changes in bowel habit, or crampy left lower quadrant discomfort. **

Figure 17-60 Schematic of the morphologic and molecular changes in the adenoma-carcinoma sequence. It is postulated that loss of one normal copy of the tumor suppressor gatekeeper gene APC occurs early. Indeed, individuals may be born with one mutant allele of APC, rendering them extremely likely to develop colon cancer. This is the "first hit," according to Knudson's hypothesis. The loss of the normal copy of the APC gene follows ("second hit"). Mutations of the oncogene K-RAS seem to occur next. Additional mutations or losses of heterozygosity inactivate the tumor suppressor gene p53 (on chromosome 17p) and SMAD2 and SMAD4 on chromosome 18q, leading finally to the emergence of carcinoma, in which additional mutations occur. It is important to note that while there seems to be a temporal sequence of changes, as shown, the accumulation of mutations, rather than their occurrence in a specific order, is more important.Downloaded from: StudentConsult (on 24 February 2010 11:38 PM) 2005 Elsevier **

dr rena normasari

Figure 17-61 Carcinoma of the cecum. The fungating carcinoma projects into the lumen but has not caused obstruction.Downloaded from: StudentConsult (on 24 February 2010 11:38 PM) 2005 Elsevier **

dr rena normasari

Figure 17-62 Carcinoma of the descending colon. This circumferential tumor has heaped-up edges and an ulcerated central portion. The arrows identify separate mucosal polyps.Downloaded from: StudentConsult (on 24 February 2010 11:38 PM) 2005 Elsevier **

dr rena normasari

Figure 17-63 Invasive adenocarcinoma of colon, showing malignant glands infiltrating the muscle wall.Downloaded from: StudentConsult (on 24 February 2010 11:38 PM) 2005 Elsevier **

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Tumor (T)T0 = none evidentT1 = invasion of lamina propria or submucosaT2 = invasion of muscularis propriaT3 = invasion through muscularis propria into subserosa or nonperitonealized perimuscular tissueT4 = invasion of other organs or structures

Lymph Nodes (N)0 = none evident1 = 1 to 3 positive pericolic nodes2 = 4 or more positive pericolic nodes3 = any positive node along a named blood vessel

Distant Metastases (M)0 = none evident1 = any distant metastasis

Figure 17-64 Pathologic staging of colorectal cancer. Staging is based on the depth of tumor invasion.Downloaded from: StudentConsult (on 24 February 2010 11:38 PM) 2005 Elsevier **

dr rena normasari

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results from the retention of bile.Bilirubin is the end product of heme degradation; heme oxygenase oxidizes heme to biliverdin, which is then reduced to bilirubin by biliverdin reductase. Bilirubin thus formed outside the liver in cells of the mononuclear phagocyte system (including the spleen) is released and bound to serum albumin. **

In the normal adult the rate of systemic bilirubin production is equal to the rates of hepatic uptake, conjugation, and biliary excretion. Jaundice occurs (bilirubin levels may reach 30-40 mg/dL in severe disease) when the equilibrium between bilirubin production and clearance is disturbed(1) excessive production of bilirubin, (2) reduced hepatic uptake, (3) impaired conjugation, (4) decreased hepatocellular excretion, and (5) impaired bile flow (both intrahepatic and extrahepatic). **

BloodConjugated & ConjugatedUrine Urobilinogen Stool Stercobilin**

Post Hepatic (Obstructive) Stone, tumorConjugated/Direct Bil, High colored urine, Pre Hepatic (Acholuric) - HemolyticUnconjugated/Indirect Bil, pale urineHepatocellular Jaundice - Viral Liver damage - unconjugatedSwelling, canalicular obstruction - ConjugatedConjugated & Unconjugated types.

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Cholestasis, which results from impaired bile flow due to hepatocellular dysfunction or intrahepatic or extrahepatic biliary obstruction, may also present as jaundice. However, sometimes pruritus is the presenting symptom, Skin xanthomas**

Hepatic Failure The alterations that cause liver failure fall into three categories: Acute liver failure with massive hepatic necrosis. Chronic liver disease. Hepatic dysfunction without overt necrosis. **

Jaundice is an almost invariable finding. Impaired hepatic synthesis and secretion of albumin leads to hypoalbuminemia, which predisposes to peripheral edema. Hyperammonemia is attributable to defective hepatic urea cycle function. On a longer term basis, impaired estrogen metabolism and consequent hyperestrogenemia are the putative causes of palmar erythema (a reflection of local vasodilatation) and spider angiomas of the skin. **

In the male, hyperestrogenemia also leads to hypogonadism and gynecomastia. Hepatic failure is life-threatening for several reasons. The accumulation of toxic metabolites may have widespread effects. With severely impaired liver function, patients are highly susceptible to failure of multiple organ systems.

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Thus, respiratory failure with pneumonia and sepsis combines with renal failure to claim the lives of many individuals with hepatic failure. A coagulopathy develops, attributable to impaired hepatic synthesis of blood clotting factors. Intestinal absorption of blood places a metabolic load on the liver that worsens the severity of hepatic failure. **

disturbances in brain function, ranging from subtle behavioral abnormalities to marked confusion and stupor, to deep coma and death.Associated fluctuating neurologic signs include rigidity, hyper-reflexia, nonspecific electroencephalographic changes, and, rarely, seizures. **

Two physiologic conditions seem to be important in the genesis of this disorder: (1) severe loss of hepatocellular function and (2) shunting of blood from portal to systemic circulation around the chronically diseased liver. In the acute setting, an elevation in blood ammonia, which impairs neuronal function and promotes generalized brain edema**

development of renal failure without primary abnormalities of the kidneys themselves.Damage to both liver and kidney, as may occur with exposure to carbon tetrachloride and certain mycotoxins, and the copper toxicity of Wilson disease. circulatory collapse leads to acute tubular necrosis and renal failure. The ability to concentrate urine is retained, producing a hyperosmolar urine devoid of proteins and abnormal sediment**

diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules.Its three main characteristics are: Bridging fibrous septa ,Parenchymal nodules

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The major mechanisms that combine to create cirrhosis are hepatocellular death, regeneration, progressive fibrosis, and vascular changes. The development of cirrhosis requires that cell death occur over long periods of time and be accompanied by fibrosis. All forms of cirrhosis may be clinically silent. When symptomatic they lead to nonspecific manifestations: anorexia, weight loss, weakness, and, in advanced disease, frank debilitation. **

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Fibrosis

Regenerating Nodule**

Portal hypertension in cirrhosis results from increased resistance to portal flow at the level of the sinusoids and compression of central veins by perivenular fibrosis and expanded parenchymal nodules. The four major clinical consequences are (1) ascites, (2) the formation of portosystemic venous shunts, (3) congestive splenomegaly, and (4) hepatic encephalopathy**

Ascites refers to the collection of excess fluid in the peritoneal cavity. The pathogenesis of ascites is complex, involving one or more of the following mechanisms: Sinusoidal hypertension, alters Starling forces and drives fluid into the space of Disse, which is then removed by hepatic lymphatics; this movement of fluid is also promoted by hypoalbuminemia.

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Leakage of hepatic lymph into the peritoneal cavity: normal thoracic duct lymph flow approximates 800 to 1000 mL/day. With cirrhosis, hepatic lymphatic flow may approach 20 L/day, exceeding thoracic duct capacity. Renal retention of sodium and water due to secondary hyperaldosteronism

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With the rise in portal venous pressure, bypasses develop wherever the systemic and portal circulations share capillary beds. Principal sites are veins around and within the rectum (manifest as hemorrhoids), the cardioesophageal junction (producing esophagogastric varices), the retroperitoneum, and the falciform ligament of the liver (involving periumbilical and abdominal wall collaterals). Abdominal wall collaterals appear as dilated subcutaneous veins extending outward from the umbilicus (caput medusae)**

Long-standing congestion may cause congestive splenomegaly. Massive splenomegaly may secondarily induce a variety of hematologic abnormalities attributable to hypersplenism**

Three major etiologic associations have been established: infection with HBV or HCV, chronic alcoholism, and aflatoxin exposure. rapid increase in liver size, sudden worsening of ascites, or the appearance of bloody ascites, fever, and pain call attention to the development of a tumor.

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The overall prognosis of HCC is grim, but it is significantly better for individuals who have a single tumor less than 2 cm in diameter and good liver function. The median survival is 7 months, with death from (1) profound cachexia, (2) gastrointestinal or esophageal variceal bleeding, (3) liver failure with hepatic coma, or (4) rarely, rupture of the tumor with fatal hemorrhage. **

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dr rena normasari

Bile is the only significant pathway for elimination of excess cholesterol from the body, either as free cholesterol or as bile salts.Cholesterol is water insoluble and is rendered water soluble by aggregation with bile salts and lecithins secreted into bile. When cholesterol concentrations exceed the solubilizing capacity of bile (supersaturation), cholesterol can no longer remain dispersed and nucleates into solid cholesterol monohydrate crystals. **

70% to 80% remain asymptomaticAge and gender, Ethnic and geographic, Heredity, Environment. Estrogenic influences, including oral contraceptives and pregnancy, increase hepatic cholesterol uptake and synthesis, leading to excess biliary secretion of cholesterol. Obesity, rapid weight loss, and treatment with the hypocholesterolemic agent clofibrate are also strongly associated with increased biliary cholesterol secretion.

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Inflammation of the gallbladder ,occurs in association with gallstones.In acute cholecystitis the gallbladder is usually enlarged (twofold to threefold) and tense, and it assumes a bright red or blotchy, violaceous to green-black discoloration, imparted by subserosal hemorrhagesin chronic cholecystitis are extremely variable and sometimes minimal.

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Acute calculous cholecystitis may barely achieve notice or may announce itself acutely, with severe, steady upper abdominal pain often radiating to the right shoulder. Chronic cholecystitis does not have the striking manifestations of the acute forms and is usually characterized by recurrent attacks of either steady or colicky epigastric or right upper quadrant pain. The diagnosis by ultrasonography, typically accompanied by evidence of a thickened gallbladder wall.

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Choledocholithiasis presence of stones within the biliary tree.Symptoms may develop because of (1) biliary obstruction, (2) pancreatitis, (3) cholangitis, (4) hepatic abscess, (5) chronic liver disease with secondary biliary cirrhosis, or (6) acute calculous cholecystitis.**

acute inflammation of the wall of bile ductscaused by bacterial infection of the normally sterile lumen. The usual pathogens are E. coli, Klebsiella, Clostridium, Bacteroides, or Enterobacter; parasitic cholangitis; Fasciola hepatica or schistosomiasis, Clonorchis sinensis or Opisthorchis viverrini, and cryptosporidiosis in individuals with acquired immunodeficiency syndrome. **

fever, chills, abdominal pain, and jaundice. The most severe form of cholangitis is suppurative cholangitis, in which purulent bile fills and distends bile ducts, with an attendant risk of liver abscess formation. **

a complete obstruction of bile flow caused by destruction or absence of all or part of the extrahepatic bile ducts. (1) inflammation and fibrosing stricture of the hepatic or common bile ducts; (2) inflammation of major intrahepatic bile ducts, with progressive destruction of the intrahepatic biliary tree; **

(3) florid features of biliary obstruction on liver biopsy (i.e., marked bile ductular proliferation, portal tract edema and fibrosis, and parenchymal cholestasis); and (4) periportal fibrosis and cirrhosis within 3 to 6 months of birth.

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Stools change from initially normal to acholic as the disease evolves. a liver biopsy provides evidence of bile duct obstruction in 90% of cases of biliary atresia. Liver transplantation remains the definitive treatment. Without surgical intervention, death usually occurs within 2 years of birth. **

more common in women and occurs most frequently in the seventh decade of life. cancers of the gallbladder assume either exophytic or infiltrating patterns of growth. a poorly defined area of diffuse thickening and induration of the gallbladder wall that may cover several square centimeters or involve the entire gallbladder. **

The exophytic pattern grows into the lumen as an irregular, cauliflower mass, but at the same time it invades the underlying wallMost carcinomas of the gallbladder are adenocarcinomas. About 5% are squamous cell carcinomas or have adenosquamous differentiation.

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most have invaded the liver directly and many have extended to the cystic duct and adjacent bile ducts and portal hepatic lymph nodes. abdominal pain, jaundice, anorexia, and nausea and vomiting. The fortunate person develops early obstruction and acute cholecystitis before extension of the tumor into adjacent structures**

adenocarcinomas with biliary differentiation arising from cholangiocytes in ducts within and outside of the liver. the prognosis is poor and most patients have unresectable tumors. Risk factors include primary sclerosing cholangitis, fibrocystic diseases of the biliary tree**

more or less well-differentiated adenocarcinomas, typically with an abundant fibrous stroma (desmoplasia) explaining their firm, gritty consistencyrisk factors :chronic cholestasis and inflammation. a liver mass and unspecific symptoms such as weight loss, pain, anorexia, and ascites. **

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