Chronic cholecystitis and cholelithiasis

Chronic

Cholecystitis Max J. Palayew,

CHOLECYSTITIS

C

HRONIC cholecystitis may be defined as a chronic or recurrent inflammation of the gallbladder usually associatedwith the presenceof cholelithiasis.At times, cystic duct obstruction is a precursor. Chronic choiecystitis is characterized symptomatically by fatty i‘ood intolerance, constant or intermittent postprandial epigastric or right upper quadrant distress, belching, nausea,vomiting, and flatulence, with or without attacks of biliary colic. Pathologically, the gallbladder may show minimal to severechronic inflammatory changes-from mucosalscarringto severetransmural fibrosis with, on occasion, calcification of the wa11.14The galibladder size may be normal, increased, or decreased depending on the variable forces of obstruction. infection, and fibrosis. The wall is almost always thickened. Adhesionsto adjacent structures may be present. Gallstones are present in 90%-95% of the patients. When stonesare absent, the cholecystitis is thought to be on an infectious basisor due to gallstones that later passed.Perforation of the gailbladder into adjacent bowel may lead to chronic cholecystoenteric fistula. This complication aswell asmalignant degenerationis fortunately rare. CHOLELITHIASIS

Cholelithiasis is a common and seriousclinical problem in the LJnited States and Canada,where IO%-20% of adults have gallstones.14Women are affected at least twice asfrequently asmen,6 with pregnancy thought to play a role, becauseof stasis. The prevalence increaseswith age in both sexes and is highest in the American Indian, in whom 50% of the adult population hascholelithiasis.” There is also an increasein frequency of cholelithiasisin certain patient populations: (1) Postvagotomy patients have been reported Max J. Palayew, M.D., F.R.C.P.(C): Radiologist-in-Chief, Jewish General Hospital, and Associate Professor of Radiology, McGill University, Montreal. Canada. Reprint requests should be addressed to Max J. Palayew, M.D., F.R.C.P.(C), Jewish General Hospital, 375.5 Cote St. Catherine Rd., Montreal, Canada. 0 1976 by Grune 1%Stratton, Inc. Seminars

in Roentgenology,

Vol.

Xl,

No.

4 (October),

1976

and Cholelithiasis M.D., F.R.C.P.(C)

to have a higher incidence of cholesterol stones.12~‘8 (2) About a third of patients with regional enteritis involving the terminal ileum have gallstones.4jg It is speculated that malabsorption of bile salts leads to a lowering of the concentration of bile acids relative to cholesterol in hepatic bile, favoring the precipitation of cholesterol crystals and the formation of gal1stones.a (3) Diabetics are said to have an increased incidence of gallstones.‘4The reasonis unktlown. (4) Calcium bilirubinate stonesare seenwith increasedfrequency in patients with sickle cell anemia or thalassemia,as a result of increasedred blood cell destruction. (5) Cholelithiasis is more common III patients with cirrhosisof the liver than in the generalpopulation.” Classificationof Cholelithiasis Gallstonesare predominantly of two types, cholesterol and calcium bilirubinate. A third type, calcium carbonate, is rare. Stones are of mixed type in approximately 90% of cases.Cholesterol stones are rarely pure and often contain a nidus of calcium bilirubinate. Pure cholesterol stonescontain 96% or more of cholesterol; mixed stonestisually contain over 70% cholesterol. Bilirubin stonesare made up of 40%-60% calcium bilirubinate and from tracesup to 35%)of cholesterol.I9 Pathogenesiso.f Gallstone Formation Cholesterol stones. Two steps are involved in the formation of cholesterol stones.““6”7 ( 1) The capacity of bile to maintain solubility of cholesterol is exceeded and insoluble microcrystals precipitate from solution. (2) These microcrystals unite to form a macroscopicgallstone. These two processesproceed simultaneously. Normal bile is an aqueoussolution with conjugated bile salts,lecithin, and cholesterol comprising up to 95% of the total solids dissolvedtherein. Cholesterol (a neutral sterol) and lecithin (a phospholipid) are almost completely insoluble in water, but bile saltsare able to form multimolecular aggregatesor micelles, which render lecithin and cholesterol solublein an aqueoussolutioll. 249

MAX

Fig. 1. Larga solitary in a normally functioning logic diagnosis: chronic cholelithiasis.

An aqueous micellar solution of bile salts plus lecithin is approximately seven times more efficient in rendering cholesterol soluble than is a bile salt solution alone; hence, the importance of lecithin in this process. In the presence of an imbalance of these three substances, i.e., a relative increase in cholesterol, or decrease in bile salts or lecithin, precipitation of cholesterol may occur. This hypothesis has been confirmed in vitro. Vlahcevic et al. *’ have shown that patients with cholesterol calculi not only have a decreased bile salt pool, but also excrete a decreased daily amount of bile salts. Since all the lecithin and most of the cholesterol excreted by the liver are closely linked to bile salt excretion, hepatic lecithin excretion is also reduced. The fraction of cholesterol that is independent of bile salt excretion remains unchanged. It is evident, then, that the net result of imbalance of cholesterol, bile salts, and lecithin may produce a bile solution that is saturated or supersaturated with cholesterol. Studies of bile from patients with cholesterol gallstones do indeed show either saturation or supersaturation with cholesterol relative to the concentration of bile salts or lecithin. Similar changes are also noted in the hepatic bile before it reaches the gallbladder.” It is proposed, therefore, that cholesterol stones are the result of faulty bile formation in the liver. In the gallbladder, when an element of stasis is added, the individual microcrystals of cholesterol coalesce around a pigment or mucus nidus to form a macroscopic stone. The gallbladder acts as a reservoir, providing the stasis and increased mucous secretion that favors the growth of a macroscopic gallstone.

J.

PALAYEW

cholesterol gallbladder. cholecystitis

calculus Pathowith

Calcium bilirubinate stones. These stones comprise from 5% to 20% of stones in the United States and Canada but represent 30%-40% of all gallstones in Japan.” The stones contain from 40% to 60% bilirubin. As previously noted, they are often found in patients who have hemolytic anemia. In Japan, cultures of bile from patients with calcium bilirubinate calculi have invariably grown Escherichia coli. Eggs or fragments of cuticles of ascaris lumbricoides are found in the calculi in 55% of the cases, and ascaris eggs frequently form

Fig. 2. Multiple mixed calculi in a distended functioning gallbladder. Note pressure effect anterior portion of the hepatic flexure (arrows).

on

nonthe

CHOLECYSTITIS

Fig. 3.

Unusual

AND

spindle-shaped

251

CHOLELITHIASIS

opaque

calculus.

the nidus for calcium bilirubinate stone formation in these patients. In Vietnam, 70% of gallstones are shown to have roundworm elements as a central nidus.” The bilirubin in these calculi is nonconjugated. Since the bilirubin in bile is normally conjugated, the stone bilirubin must have undergone deconjugation by the action of the enzyme B-glucuronidase, which is present only in bile infected with I?. coli. When bile is infected with E. coli, the organism releasesB-glucuronidase, which for-rns free bilirubin. the carboxyl radical of which combines with calcium to form calcium bilirubinate. This mechanism has been demonstrated in vitro by Maki.”

Fig. 4. A solitary calculus impacted in Hartmann’s pouch or cystic duct (upper arrow) with multiple mixed calculi in a grossly distended gallbladder (lower arrows).

Fig. 5. Milk calculus. Plain

of film.

calcium

bile

with

a large

radiopaque

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MAX

J.

PALAYEW

Calcium carbonate stones. These stones are rare in pure form. Increased electrolytes, especially calcium, increased alkalinity, and stasis of bile are thought to favor precipitation of calcium carbonate. This theory is speculative. RADIOGRAPHIC CHOLECYSTITIS

FINDINGS IN CHRONIC AND CHOLELITHIASIS

Calculi, radiopaque or radiolucent, are found in all shapesand sizes.Cholesterol stonesare usually round to oval and are often solitary (Fig. 1). Mixed stones are often multiple and may be faceted (Fig. 2). Plain Film Findings

Fig. 6. Milk in gallbladder.

of calcium Plain film.

bile

with

Fig. 7. Milk of calcium bile. (A) gallbladder is faintly opaque (lower culus in the cystic duct (upper arrow)

multiple

lucent

calculi

Soft-tissue mass. The distended gallbladder itself, with or without displacementof an adjacent gas-filled viscus, may be noted. Downward displacement of the anterior portion of the hepatic flexure and medial displacementof the descending duodenum are often seen(Fig. 2). Radiopaque calculi (Figs. 3 and 4). These are due to calcium bilirubinate, calcium carbonate, or mixed calculi, the latter predominating by far. Milk of calcium bile. Milk of calcium bile (“limy bile”) can be seenon plain films, whether or not it

Recumbent plain film demonstrating arrow). (B) Upright film. Layering has not shifted.

small calculus in cystic of the opaque bile is shown

duct (upper arrow). The (lower arrow). The cal-

CHOLECYSTITIS

Fig. contour bladder

8.

Porcelain and the (arrow).

AND

break

CHOLELITHIASIS

gallbladder. in the

rim

Note in the

253

the neck

pear-shaped of the gall-

contains lucent or opaque calculi (Figs. 5 and 6). It results from deposition of calcium salts in the bile secondary to cystic duct obstruction. Layering is demonstrable in the upright or decubitus view (Fig. 7). If the entire gallbladder is filled with milk of calcium bile, it may be mistakenly reported on oral cholecystography as a normal gallbladder, if no plain film is available. Calcified (porcelain) gallbladder. Calcification of the gallbladder wall is always associatedwith cystic duct obstruction. The calcium lies in the submucosa.Classically,the calcific contour ISpearshaped with a break in the region of Hartmann’s pouch (Fig. 8). At times. only a segmentof the circumference is calcified. The differential diagnosisincludes a large calcitied gallstone, aneurysm of the hepatic or renal artery, calcified echinococcuscyst, and renal cyst. Recent reports suggestan increasedinctdence of carcinoma in patients with calcification of the gallbladder wa11.2 Calculi with ten tral fissuring ( licrow ‘s-foot” or “Mercedes Benz” sign]. This sign, recently reem-

phasized by Meyers and O’Donohue,” is indicated by a stellate radiolucency in the gallbladderregion. It may represent the only finding of cholelithiasis

254

MAX

Fig.

10.

Gallstones

only

apparent

on the plain film. I have been able to suggest the diagnosis of gallbladder pathology on the basis of this sign in several patients in whom the diagnosis was unsuspected (Fig. 9). Gas in the center of such calculi has been demonstrated by breaking them under water. Gas. Air or an air-fluid level may be demonstrated in the lumen of a gallbladder that is communicating with the gastrointestinal tract. The fis-

on upright

film.

(A)

Prone.

(6)

J.

PALAYEW

Upright.

tula may be the result of surgery, perforated gallstone, perforating carcinoma, or peptic ulcer. Acute emphysematous cholecystitis will be discussed elsewhere in this Seminar. Findings on Contrast Studies Oral cholecystography. When performed as indicated in Part I of this Seminar (p. l&5), a nonvisu-

Fig. , 11. film. These

Floating were

not

calculi visible

layered on the

on up1 recuml

CHOLECYSTITIS

AND

CHOLELITHIASIS

Fig. 12. Intravenous cholangiogram 2 hr after injection. A normal common bile duct is seen with passage of contrast medium into the duodenum. The gallbladder is not visualized. The pathologic diagnosis was chronic cholecystitis and cholelithiasis.

alized gallbladder, especially if associated with visible common bile duct, is virtually diagnostic of cystic duct obstruction. A faintly visualized gallbladder without calculi may be evidence of noncalculous cholecystitis. Duodenal drainage for

Fig. fistula proved.

13. in

Spontaneous an elderly

cholecystocolic woman. Surgically

255

crystals may be helpful in establishing this diagnosis. A normally visualized gallbladder may also occasionally show chronic noncalculous cholecystitis on pathologic examination. The causes of a nonvisualized gallbladder are listed in the appended gamut. Radiolucent, radiopaque, or mixed calculi are usually demonstrable in a functioning gallbladder. However, there is always the danger of the contrast medium obscuring radiopaque calculi (Fig. 9B). Upright or decubitus films must be obtained routinely to avoid this error (Fig. 10). Floating calculi may simulate layering of bile or contrast medium (Fig. 11). When difficulty arises, careful fluoroscopic examination and postfatty meal fluoroscopic studies will usually facilitate the differentiation. A fluid-filled antrum or duodenal bulb may also on occasion simulate a faintly outlined gallbladder especially on intravenous cholangiography. Awareness of this finding may be of paramount importance. AP or PA views or a barium study of the antrum and bulb are occasionally required to solve this dilemma. Intravenous cholangiography. The demonstration of the common bile duct accompanied by failure to visualize the gallbladder on films taken up to 2 hours following the intravenous administration of contrast medium is virtually diagnostic of obstruction of the cystic duct (Fig. 12). Other in-

256

MAX

J. PALAYEW

dications for intravenous cholangiography are discussedin Part I of this Seminar (p. 197). Barium studies. These studies are frequently helpful in outlining a fistula between the gastrointestinal tract and the gallbladder(Figs. 13 and 14). A pressure effect of the enlarged gallbladder on the duodenum or on the anterior portion of the hepatic flexure may be clearly delineated on appropriate films. Adhesions of the gallbladder to the colon or duodenum may simulate either primary or extrinsic neoplastic or inflammatory conditions of thesestructures.‘y2’

Fig. 14. Cholecystoduodenal fistula had a subtotal gastrectomy for peptic previously. The gallbladder is outlined also visible in the biliary tree.

GAMUT

in a patient ulcer several by arrows.

ACKNOWLEDGMENT I am grateful to Drs. Lawrence Stein. and France Bourdon-Conachie for permission to use their cases, to Mr. Nathan Feifer for photography, and to Miss. Martha Byron for typing the manuscript.

who years Air is

OF NONVISUALIZED Nonvisualization

GALLBLADDER13

of the Gallbladder

Common (1) [Calcified gallbladder wall; milk of calcium] (2) Calculus obstructing cystic duct or infundibulum (e.g., hydrops, empyema) (3) Cholecystitis (4) Failure to take contrast material (5) Gallbladder stasis (6) Liver disease with hepatocellular damage (e.g., hepatitis, cirrhosis) (7) Obstruction of esophagusor pylorus (8) Obstructive jaundice (e.g., carcinoma of pancreas,stone in common duct)

(9) Prior cholecystectomy (10) Vomiting, diarrhea

Uncommon (1) [Anomalous position of gallbladder] (2) Carcinoma of gallbladder (3) Congenital absence (4) Obliterative fibrosis of gallbladder (5) Retention of contrast medium in a diverticulum or in an obstructed stomach (e.g., diabetic gastropathy)

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miology of gallbladder disease: Observations in the Framingham study. J Chronic Dis 19:273-292, 1966 7. Ghahremani GG, Meyers MA: The cholecysto-colic relationships: A roentgen-anatomic study of the colonic manifestations of gallbladder disorders. Am J Roentgen01 125:21-34, 1975 8. Gregory DH: Determination of the cholesterol saturation of human bile and its relevance to gallstone formation. Am J Dig Dis 19:268-270, 1974 9. Heaton KW, Read AE: Gallstones in patients with disorders of the terminal ileum and disturbed bile salt metabolism. Br Med J 3:494-496, 1969 10. Maki T: Pathogenesis of calcium bilirubinate gallstone: Role of E. Coli, B-glucuronidase and coagulation by inorganic ions, polyelectrolytes and agitation. Ann Surg 164:90-loo,1966

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11. Meyers MA, O’Donohue N: The Mercedes-Benz sign: Insight into the dynamics of formation and disappearance of gdllStOrleS. Am J Roentgen01 119:63-70, 1973 12. Miller MC: Cholelithiasis developing after vagotomy: A preliminary report. Can Med Assoc J 98 (Part 1): 350-354, 1968 13. Reeder MM, F’elson B: Gamuts in Radiology. Cincinnati, Audiovisual Radiology of Cincinnati, 1975 14. Robbins SL: Textbook of Pathology. Philadelphia, Saunders, 1974 1.5. Sampliner RE, Bennett PH, Comess LJ, et al: Gallbladder disease in Pima Indians-demonstration of high prevalence and early onset by cholecystography. N Engl J Med 283: 1358-1364, 1970 16. Sleisenger MH. Fordtran JS: Gastrointestinal disease. Philadelphia, Saunders, 1973, pp 1110-l 128

257 17. Small DM, Rapo S: Source tients with cholesterol gallstones. 57,197o 18. Tompkins RK, Kraft AR, Clinical and biochemical evidence formation after complete vagotomy. 1972

of abnormal bile in paN Engl J Mcd 283:53Zimmerman 1,. et al: of increased gallstone Surgery 7 I : 196-200,

19. Trotman BW, Ostrow JD, Soloway RD: Pigment vs. cholesterol cholelithiasis: Comparison of stone and bile composition. Am J Dig Dis 19:585-590, 1974 20. Vlahcevic ZR, Bell CC, Buhac I, et al: Diminished bile acid pool size in patients with gallstones. Gastroenterology 59:165-173, 1970 21. Whalen JP: Anatomy of the colon: Guide IO intraabdominal pathology. Hickey Lecture 1975. Am J Roentgenol 125:3-20. 1975