Gallbladder Disease in Children

1. Gallbladder Disease in Children Laredo Pediatrics & Neonatology PA Francisco J Cervantes MD, FAAP www.LaredoPediatrics.com August 24 th 2012 Driscoll Children’s Hospital Corpus Christy TX

2. Conflict of Interest Disclosure Francisco J Cervantes MD: I or any on my immediate family have no Financial interest/arrangement or affiliation with any organization that could be perceived as real or apparent conflict of interest.

3. OBJECTIVES Provide a brief review of Bile and Gallbladder Physiology and gallstone formation Screen procedures to identify Fatty Liver and gallbladder disorders Identify Children at risk for developing Fatty Liver and Gallbladder disorders

4. The gallbladder, which has a capacity of 50 milliliters (about 5 tablespoons), concentrates the bile 10 fold by removing water and stores it until a person eats. At this time, bile is discharged from the gallbladder via the cystic duct into the common bile duct and then into the duodenum (the first part of the small intestine), where it begins to dissolve the fat in ingested food. The liver's cells (hepatocytes) excrete bile into canaliculi, which are intercellular spaces between the liver cells. These drain into the right and left hepatic ducts, after which bile travels via the common hepatic and cystic ducts to the gallbladder. Bile Formation

5. Synthesis of bile acids is a major route of cholesterol metabolism in most species other than humans. The Liver produces about 800 mg of cholesterol per day and about half of that is used for bile acid synthesis. 20-30 grams of bile acids are secreted. 90% of excreted bile acids are reabsorbed by in the ileum. Bile is also used to break down fat globules into tiny droplets.

6. Pathophysiology of Gall bladder disease Cholecystitis calculous and Acalculous. In the pediatric population most gallbladders that are removed for acute cholecystitis show evidence of chronic inflammation. Mechanism of Chronic Inflammation : cholesterol crystals and/or calcium bilirubinate→ stone →inflammation→ chronic obstruction→ decreased contractile → biliary stasis→ Inflammation of the gallbladder wall

7. Pathophysiology of Gall bladder disease Acalculus Cholecystitis: similar manner but from different etiologic most often associated with systemic illness or infection → Increased mucous production, dehydration, and increased pigment → increase cholesterol saturation and biliary stasis→ hypofunction→ biliary sludge → obstruction → inflammation, edema → compromised blood flow and bacterial infection

8. Abstract Cholesterol, the major component of Summary gallstones, is held in solution in the bile by formation of micelles in which phospholipids and bile-salts are involved. The ratio of cholesterol to bile-salts plus phospholipids determines cholesterol solubility. Although the bile produced by the liver in patients with gallstones is abnormal, some features of gallbladder function might favor stone formation. Of the hepatic factors contributing to gallstone formation a high cholesterol content of bile, a low bile-salt pool, and interruption of the enterohepatic circulation seem to be important. One hypothesis for gallstone formation relates to events at the plasma membrane of the bile canaliculus, but whether the critical factor here is an increase in the amount of cholesterol passing through the membrane or an abnormal cholesterol to phospholipid ratio remains controversial. It seems likely that an understanding of the mechanism for gallstone formation will come from an investigation of the problem at the cellular, subcellular, or molecular level. This review ends with a note on the prospects for treatment, which should be directed at affecting the cholesterol to phospholipid plus bile-salt ratio or at the cholesterol precipitate directly by using detergent agents. IanA.D Bouchier * Based on the Goulstonian Lecture delivered before the Royal College of Physicians, in London, on April 7, 1971. GALLSTONE FORMATION

9. The two types of gallstones are cholesterol stones and pigment stones. Cholesterol stones are usually yellow-green and are made primarily of hardened cholesterol. They account for about 80 percent of gallstones. Pigment stones are small, dark stones made of bilirubin. Gallstones can be as small as a grain of sand or as large as a golf ball. The gallbladder can develop just one large stone, hundreds of tiny stones, or a combination of the two TYPES OF GALLSTONES

10. women—especially pregnant, use of hormone replacement therapy, or birth control pills ( decrease gallbladder movement) people over age 60 ( As people age, the body tends to secrete more cholesterol into bile) American Indians (Pima Indians of Arizona, 70% of women have gallstones by age 30) Mexican Americans overweight or obese ( Bile salts Cholesterol GB emptying people who fast or lose a lot of weight quickly people with a family history of gallstones (possible genetic link) people with diabetes ( high levels of fatty acids called triglycerides) people who take cholesterol-lowering drugs Who is at risk for gallstones? The Classic 4 F’s still apply: F emale, F ertile, F orty, F at

11. Signs and Symptoms Typical symptoms of RUQ pain, nausea, vomiting. Tenderness to palpation or mass at RUQ Leukocytosis and jaundice The pain and tenderness are less localized in younger children Epigastric pain mimic RUQ pain Epigastric pain or discomfort postprandial Atypical presentation: Sleep apnea and sleep disturbance

12. Causes of GB disease in Children History of cardiac or abdominal surgery Prolonged parenteral nutrition Hemolytic disease Hepatobiliary obstructive disease Obesity Rapid decreases in weight Systemic Infection Acute renal failure Prolonged fasting Low calorie diet Certain medications Organ transplant

13. Gall Bladder disease in children Cholecystitis Cholelithiasis Sludge Polyps Septation Dilated or Contracted Non Specific Thickened Wall Phrygian Cap Related To: Fatty Liver Focal Fat Sparing Hyper echoic Nodes Hepatomegaly Spleen Enlargement Ascites Pleural Fluid Pancreatitis Cirrhosis?

14. Sludge Biliary Sludge is a mixture of particulate matter and mucous from the bile The composition of particulate matter varies Cholesterol Crystals and calcium Drugs particles since the bile is one of the major routes of excretion of drugs 3 Sludge has been associated with conditions: Pregnancy Rapid weight loss Medications ( ceftriaxone, Octreotide) Bone marrow and solid organ transplantation

15. Cholesterosis accumulated in the mucosal service of the GB

16. Cholesterosis might contribute to the formation of the GB polyps

17. Complete Sludge with stone formation

18. Fact about GB polyps Resembling growth in the gall bladder wall True polyps are abnormal accumulation of mucous membrane tissues that would normally be shed by the body Main types of polyps Cholesterol Polyp/Cholesterosis Cholesterosis with fibrous dysplasia Adenomyomatosis Hyperplastic cholecystosis Adenocarcinoma It affects 5% of adult, the causes uncertain, but there is a correlation between increase age, and presence of Gall stone. The polyps are detected by abdominal ultrasound performed for another reason  

19. Figure 1.  Focal hepatic steatosis. Prasad S R et al. Radiographics 2005;25:321-331 ©2005 by Radiological Society of North America

20. Diffuse fat accumulation with focal sparing at US. Transverse US image show high echogenicity features indicative of a diffuse accumulation of fat in the liver. Focal sparing ( fs ) is manifested as a geographically shaped area with relative hypoechogenicity . The focal fatty pseudolesion exerts no mass effect on the adjacent vessel Hamer O W et al. Radiographics 2006;26:1637-1653 ©2006 by Radiological Society of North America

21. Figure 7.  Focal fat accumulation in the liver at US. Transverse image shows, adjacent to the left portal vein, a geographically shaped area of high echogenicity that represents accumulation of fat (f) in the falciform ligament, with posterior acoustic attenuation. Hamer O W et al. Radiographics 2006;26:1637-1653 ©2006 by Radiological Society of North America

22. Septate gallbladder is a very rare anomaly that has an asymptomatic course and is detected as an incidental finding without clinical relevance. Rarely, however, septate gallbladder causes recurrent attacks abdominal pain or becomes complicated by cholelithiasis. The pinpoint communication between the cavities causes stagnation, inflammation or stone formation. Symptoms are usually caused by pressure in the small chambers of the gallbladder along with delayed emptying which may sometimes favor early Cholecystectomy Ultrasonography is the modality of choice. Gall bladder septation

23. Feldhauptmanns Alessandro del Borro 1645 During the Middle Ages Obesity was often seen as sign of wealth, and was relatively common among the elite

24. Present time: Obesity is a medical condition in which excess body fat has accumulated to the extend that it may have an adverse effect on health

25. BMI Charts

26. Adult Unisex BMI Chart

27. Beginning of the Story

28. Alkaline Phospatase by Age

29. Patient Distribution by Age and BMI

30. Local Experience 2116 patients, about equally divided, boys (1041, 49.2%) and girls (1075, 50.8%) First generation American-born children of Hispanic descend. Patients were followed because of changes in BMI then the discovery of the fatty liver and subsequently Gallbladder disease. All patients have at least one metabolic screen. BMI groups normal BMI 75, 85, 95,97 and ≥99 WWW.Laredopediatrics.com

31. Total number of patient distributed according to the BMI group and sex

32. Statistical Analysis of BMI Distribution