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CHOLELITHIASIS Morphology

- Majority are “silent”, and most individuals remain free of biliary pain or other complications for Cholesterol stones
decades - Arise exclusively in gallbladder
- Two classes: - 100% pure (rare) to 50% cholesterol
o Cholesterol stones — 50% crystalline cholesterol monohydrate - Pure cholesterol stone
o Pigment stones — predominantly of bilirubin calcium salts o pale yellow, round to ovoid, finely granular, hard external surface
o on transection: glistening radiating crystalline palisade
Prevalence and Risk Factors o With increasing proportions of calcium carbonate, phosphates, and bilirubin à
- Cholesterol gallstones à US and Western Europe; uncommon in developing countries stones take on a gray-white to black color and may be lamellated
- Pigment gallstones à Non-Western population; arise primarily in the setting of bacterial infections o Multiple stones are usually present that range up to several centimeters in diameter
of biliary tree and parasitic infestations o Rarely, a very large stone may virtually fill the fundus
o Surfaces of multiple stones may be rounded or faceted, because of tight apposition.
Major risk factors o Stones composed largely of cholesterol are radiolucent
- Age and sex § sufficient calcium carbonate is found in 10% to 20% of cholesterol stones
o Prevalence increases throughout life, but predominantly affect middle to older age to render them radiopaque.
o Prevalemce higher in females in any region or ethnicity Pigment gallstones
o Hypersecretion of biliary cholesterol à Major role in both age and gender - brown to black
differences - black pigment stones à sterile gallbladder bile
o Associated with metabolic syndrome and obesity - brown stones à infected large bile ducts
- Environmental factors - Black stones contain oxidized polymers of the calcium salts of unconjugated bilirubin, small
o Estrogen exposure (pregnancy and OC) increases expression of hepatic lipoprotein amounts of calcium carbonate, calcium phosphate, and mucin glycoprotein, and some cholesterol
receptors and stimulates hepatic HMG CoA reductase activity — enhance both monohydrate crystals. Brown stones contain similar compounds along with some cholesterol and
cholesterol uptake and biosynthesis respectively calcium salts of palmitate and stearate. The black stones are rarely greater than 1.5 cm in
o Obesity and rapid weight loss are strongly associated with increased biliary cholesterol diameter, are almost invariably present in great number (with an inverse relationship between size
secretion and number; Fig. 18-63), and are quite friable. Their contours are usually spiculated and molded.
- Acquired disorders Brown stones tend to be laminated and soft and may have a soaplike or greasy consistency.
o Gallbladder stasis (neurogenic or hormonal) Approximately 50% to 75% of black stones are radiopaque due to calcium salts while brown
§ Fosters local environment that is favorable for both cholesterol and pigment stones, containing calcium soaps, are radiolucent.
gallstone formation Black pigment stones Brown stones
- Hereditary factos Sterile gallbladder bile Infected large bile ducts
o Genes encoding hepatocyte proteins that transport biliary lipids — ABC Contain: Contain:
TRANSPORTERS - oxidized polymers of calcium salts of - Similar compounds + cholesterol and
o ABCG8 gene — increased risk for development of cholesterol gallstone unconjugated bilirubin calcium salts of palmitate and
Pathogenesis: Cholesterol stones - Calcium carbonate (small amount) stearate
Cholesterol - Mucin glycoprotein
- Rendered soluble in bile by aggregation with water soluble bile salts and water insoluble lecithins - Cholesterol monohydrate (some)
à Act as detergents >1.5cm in diameter
- When cholesterol concentrations exceed solubilizing capacity of bile (supersaturation) à Present in great number (inverse relationship
Cholesterol no longer dispersed à Nucleates into solid cholesterol monohydrate crystals between size and number)
- Contribute to formation: Friable Laminated and soft
o Supersaturation of bile with cholesterol
Contours are spiculated and molded Soaplike greasy consistency
o Hypomotility of gallbladder
(50-75%) Radioopaque à Calcium salts Radiolucent à Calcium soaps
o Accelerated cholesterol crystal nucleation
o Hypersecretion of mucus in gallbladder Mucin glycoproteins constitute the scaffolding and interparticle cement of all types of stones.
Clinical Features
Pathogenesis: Pigment Stones
- Complex mixtues of insoluble calcium salts of unconjugated bilirubin along with inorganic calcium - may be present for decades before symptoms develop, and 70% to 80% of patients remain
asymptomatic throughout their lives
slats
- Associated disorders with elevated unconjugated bilirubin in bile - Asymptomatic individuals probably convert to being symptomatic at a rate of up to 4% per year,
o Chronic hemolytic anemia although the risk diminishes with time
- biliary colic
o Severe ileal dysfunction or bypass
o Bacterial contamination of biliary tree o Prominent manifestation
o constant and not colicky
- Unconjugated bilirubin
o Minor component of bile o follows a fatty meal which forces a stone against the gall bladder outlet leading to
o Increases when infection leads to release of microbial B-glucoronidases à Hydrolyze increased pressure in the gall bladder causing pain
o localized to right upper quadrant or epigastrium that may radiate to the right
bilirubin glucoronides
- Infection of biliary tract with E.coli, A.lumbricoides, C.sinensis à Increase likelihood of pigment shoulder or the back
o severe complications: empyema, perforation, fistulas, inflammation of the biliary tree
stone formation
- Hemolytic anemia (cholangitis), obstructive cholestasis and pancreatitis
o Secretion of conjugated bilirubin into bile increases - The larger the calculi, the less likely they are to enter the cystic or common ducts to produce
obstruction; very small stones, or “gravel,” à more dangerous
- 1% of bilirubin glucoronides deconjugated in biliary tree
- in the setting of chronically increased secretion of conjugated bilirubin, there is large amount of - Occasionally a large stone may erode directly into an adjacent loop of small bowelà intestinal
obstruction (“gallstone ileus” or Bouveret syndrome)
deconjugated bilirubin left to allow pigments to form
- associated with an increased risk of gallbladder carcinoma
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ACUTE APPENDICITIS o Associated with mixture of loss of vibration and position sense, sensory ataxia with
- Common in adolescents and young adults; lifetime risk of 7%; males slightly affected more than positive Romberg sign, limb weakness, spasticity, and extensor plantar responses
females - Cerebral manifestations: mild personality changes and memory loss to psychosis
- Diagnosis difficult to confirm preoperatively — confused with mesenteric lymphadenitis (often - Neuro changes NOT reversed by vitamin B12
2ndary to unrecognized Yersinia infection or viral enterocolitis), acute salpingitis, ectopic
pregnancy, mittelscherz (minor pelvic bleeding at ovulation) and Meckel diverticulitis CHOLECYSTITIS
- One of the most common indications for abdominal surgery
Pathogenesis ACUTE CHOLECYSTITIS
- Initiated by progessive increase in intraluminal pressure that compromise venous outfliw - precipitated in 90% of cases by obstruction of the neck or the cystic duct by a stone
- Associated with overt luminal obstruction à Usually caused by small stone-like mass of stool or - primary complication of gallstones and the most common reason for emergency cholecystectomy
fecaltih or gallstone, tumor, of oxyurias vermicularis - Cholecystitis without gallstones (acalculous cholecystitis)
- Stasis of luminal contents à Favors bacterial proliferation à Ischemia and inflammatory response o may occur in severely ill patients and accounts for about 10% of patients with
à Tissue edema and neutrophil infiltration of lumen, muscular wall, periappendiceal soft cholecystitis
tissues Clinical Features
- Individuals with acute calculous c cystitis usually, but not always, have experienced previous
Morphology episodes of pain
Early acute appendicitis - An attack of acute cholecystitis begins with progressive right upper quadrant or epigastric pain that
- Subsclerosal vessels à Congested with modest perivascular neutrophil infiltrate within all layers lasts for more than six hours
of wall - frequently associated with mild fever, anorexia, tachycardia, sweating, nausea, and vomiting
- Inflammatory reaction transforms serosa à Dull granular erythematous surface - Most patients are free of jaundice
- Mucosal neutrophils and focal superficial ulceration à NOT specific markers o the presence of hyperbilirubinemia suggests obstruction of the common bile duct
- Diagnosis requires neutrophilic infiltration of muscularis propria - Mild to moderate leukocytosis may be accompanied by mild elevations in serum alkaline
- Severe case: prominent neutrophilic exudate generates serosal fibrinopurulent reaction phosphatase values
- Focal abscesses may form within wall à Acute suppurative appendicitis - Acute calculous cholecystitis
- Further compromise of appendiceal vessels à Large areas of hemorrhagic ulceration and o may appear with remarkable suddenness and constitute an acute surgical emergency
gangrenous necrosis à Extend to serosa à Acute gangrenous appendicitis à Rupture and or may present with mild symptoms that resolve without medical intervention
suppurative peritonitis - In the absence of medical attention, the attack usually subsides in 7 to 10 days and frequently
Clinical Features within 24 hours
Early acute appendicitis - However, as many as 25% of patients progressively develop more severe symptoms and require
- Periumbilical pain à RLQ à Nausea, vomiting, low grade fever, mild elevated WBC ct immediate surgical intervention. Recurrence is common in patients who recover without surgery.
- McBurney sign à Deep tenderness 2/3 of distance from umbilicus to Right ASIS Clinical symptoms of acute acalculous cholecystitis
- classic signs and symptoms of acute a dicitis are often absent - tend to be more insidious. à obscured by the underlying conditions precipitating the attacks
- retrocecal appendix - higher proportion of patients have no symptoms referable to the gallbladder
o may generate right flank or pelvic pain - diagnosis therefore rests on a high index of suspicion
- malrotated colon - In the severely ill patient, early recognition of the condition is crucial, since failure to do so almost
o appendicitis in the left upper quadrant ensures a fatal outcome
- The incidence of gangrene and perforation is much higher in acalculous than in calculous
cholecystitis
- In rare instances, primary bacterial infection can give rise to acute acalculous cholecystitis, by
ROBBINS CLINICAL FEATURES
agents such as Salmonella typhi and staphylococci
Barret Esophagus
- A more indolent form of acute acalculous cholecystitis may occur in the setting of systemic
- Can only be identified through endoscopy and biopsy à Prom[ted by GERD symptoms
vasculitis, severe atherosclerotic ischemic disease in the elderly, in patients with AIDS, and with
- Intramucosal or invasive carcinoma
biliary tract infection.
o Therapeutic intervention
o Surgical resection, or esophagectomy, as well as newer modalities such as
CHRONIC CHOLECYSTITIS
photodynamic therapy, laser ablation, and endoscopic mucosectomy.
Clinical Features
- Multifocal high grade dysplasia
- does not have the striking manifestations of the acute forms and is usually characterized by
o Significant risk of progression to intramucosal or invasive carcinoma
recurrent attacks of either steady epigastric or right upper quadrant pain. Nausea, vomiting, and
o Treated as intramucosal carcinoma
intolerance for fatty foods are frequent accompaniments.
Autoimmune Gastritis
- Diagnosis of both acute and chronic cholecystitis is important because of the following
- Ab to parietal cells and intrinsic factor present early in the disease course
complications:
- Progression to gastric atrophy à 2-3 decades; anemia only in few patients
o Bacterial superinfection with cholangitis or sepsis
- Women > men
o Gallbladder perforation and local abscess formation
- Pernicious anemia and autoimmune gastritis
o Gallbladder rupture with diffuse peritonitis
o Associated with Hashimoto thyroiditis, insulin-dependent (type I) diabetes mellitus,
o Biliary enteric (cholecystenteric) fistula, with drainage of bile into adjacent organs, entry
Addison disease, primary ovarian failure, primary hypoparathyroidism, Graves disease,
of air and bacteria into the biliary tree, and potentially, gallstone-induced intestinal
vitiligo, myasthenia gravis, and LambertEaton syndrome
obstruction (ileus)
- Little evidence of linkage to HLA alleles
o Aggravation of preexisting medical illness, with cardiac, pulmonary, renal, or liver
- Neuropathic changes: demyelination, axonal degeneration, and neuronal death
decompensation
- Most common manifestation of peripheral neuropathy: paresthesias and numbnessB
o Porcelain gallbladder, with increased risk of cancer, although surveys of this risk have
- Spinal lesions à From demyelination of dorsal and lateral spinal tracts à Subacute combined
yielded widely discrepant frequencies
degeneration of the cord

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