GALLSTONES

DEFINITION
Crystalline accretions from secretions of bile.
Biliary fistulas also briefly discussed here.
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INCIDENCE

Varies by cause.
For common cholesterol stones in West:
Up to 20%F, 8%M at autopsy.

Sex
F5:M2.
Estrogens increase cholesterol uptake and biosynthesis.

Age
Increases with age, especially after 40.
5% under 40s, 30% over 80s.

Race
Europeans typically

Risk Factors
Fat, fair, forty, female.
Obesity and rapid weight loss are strongly associated.

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AETIOLOGY

Cholesterol / Mixed Stones

Pathogenesis
1. Cholesterol is excreted into bile by liver.
- is water insoluble, requires bile salts for solubility, and stabilised in solution by phospholipids.
- if ratio of salts or phospholipids to cholesterol unbalanced, then crystals form in the supersaturated bile --> 'sludge'.
- biliary hypersecretion is the primary defect (excess delivery, over-regulation).
2. Biliary hypomotility contributes to sludge.
- occurs in response to toxicity of cholesterol.
3. Cholesterol nucleates into crystals.
- sludge can be reabsorbed, or form stones at 2.6 mm/yr.
4. Mucus hypersecretion allows agglomeration of crystals into stones.
- also due to toxic effect of cholesterol
-Stones usually comprise >70% cholesterol plus some calcium salts, bile acids and bile pigments, proteins, fatty acids and phospholipids.

Congenital
IEM
Hyperlipidaemias.
Impaired hepatic synthesis of bile salts and phospholipids.

Acquired
Inflammation
Biliary cirrhosis, chronic cholestasis.
Degenerative
With age comes increased cholesterol secretion, decreased bile acid pool.
EM
Obesity esp w/ rapid weight loss (mobilises cholesterol & sludges bile).
Fasting (decreases motility).
Increased oestrogen (eg pregnancy).
TPN (decreases motility).
Trauma
Spinal cord injury - decreases motility.
Iatrogenic
Lipid lowering drugs (fibrates, statins).
Post-op, ileal resection.

Pigment Stones

Pathogenesis
From increased unconjugated bilirubin.
- normally only~0.3% of biliary solutes.
- infections increase unconjugated bilirubin from bilirubin salts (via a hydrolyzing enzyme).
- or unconjugated bilirubin may be primarily increased due to overproduction (haemolysis)
Precipitates out to form pigmented stones.
Predominantly calcium bilirubinate.

Congenital
Structural
Sickle cell anaemias, thalassaemia, spherocytosis, other hereditary haemolytic disorders.
- 75% of sickle cell and spherocystosis pts will get stones
Acquired
Inflammation
E. coli.
Parasitic (Clonorchis sinensis & Asarcis lumbroides).
Malaria (chronic haemolysis).
Degenerative
Increased in advancing age.
EM
Essentially any haemolysis.
Liver disease.
Iatrogenic
Mechanical heart valve haemolysis.
Ileal resection increases pigment secretion.

Note:
This is a little simplified.
Refer below for some detail on other pathogenetic factors.
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BIOLOGICAL BEHAVIOUR
Pathophysiology
Depends on:
1. Where it is?
2. Infected?
3. Superimposed features that caused stone?

Possible Syndromes
- 1-3% of pts with gallstones become symptomatic each year
- this decreases with time.
Gallbladder
Cholelithiasis.
Infection -> cholecystitis,.
Bile Ducts
Choledocholithiasis.
Infection -> cholangitis.
Ampulla of Vater
Pancreatitis.
Ligamentum Triez
(Results from inflamed gallbladder forming fistula with small bowel and a large stone escaping).
Small bowel obstruction.
Ileocaecal jx
As for Ligamentum Triez.
Other
Could even cause empyema, fistulation with skin, appendicitis or diverticulitis.
Mucocele / hydrops of gallbladder:
- progressive removal of luminal lipids in obstructed gallbladders
- leaves a clear mucionous secretion
Associated with higher risk of carcinoma.

Further Notes on pathogenetic factors:
Secretion
Bile is formed in the liver and actively secreted into canaliculi.
Deconjugated by bacteria in bowel, and reabsorbed by special receptors in the terminal ileum.
Return to the liver and are reconjugated.
Total of 3-4g of bile salts in the body. Rapidly circulated.
1-2% of bile salts are lost/cycle.
0.3-0.7g are produced each day to replace lost bile salts.
Maximum production is approximately 5g/day.
Secretin increases secretion of water and bicarbonate from ducts into the bile.
Somatostatin decreases secretion of bicarbonate and water.

Gall Bladder function
When the sphincter of Oddi is shut bile is diverted to the gall bladder where it is stored and concentrated (by reabsorption of Na, Cl and hence H20).
The pH falls as Na is reabsorbed in exchange for H+.
Overnight or during fasting bile salts accumulate in the gall bladder.
CCK (released in response to fats and amino acids in the duodenum) and sympthetic action increases contraction of the gallbladder and relaxes the sphincter of Oddi.
Following discharge of contents the gallbladder remains contracted to prevent storage of bile during digestion.

Gallstone Ileus
<1% of patients with cholecystitis get a biliary-enteric fistula.
- most common to duodenum, less commonly to stomach, colon, and bile duct.
Rare cause of bowel obstruction these days; only with stones >2.5cm.
Radiological features are pneumobilia, obstruction, direct / indirect visualization of stones within the tract.
- but only in 30%; CT gives the true story.
Managed by midline laparotomy, inspection for multiple stones
- retrieved as for any lodged FB by longitudinal enterotomy (on antimesenteric bowel aspect)

Should you repair the cholecystoduodenal fistula?
- controversial; classically said yes as a one stage procedure.
- but only 20% of these patients get a further problem; and dissection / repair is extensive due to inflammation and a big duodenal hole.
--> enterolithotomy alone is a suitable procedure of choice in this population.
--> series suggest lower mortality in this elderly population, with technically safer procedures and shorter hospital stay.


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MANIFESTATIONS
Seec cards of resulting syndromes.
Note that cholelithiasis, cholecystitis, choledocholithiasis and cholangitis may be differentiated by presence of:
WCC + fever.
Jaundice.
Pain.
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INVESTIGATIONS
Depends on clinical presentation (above).
- 20% of cholesterol stones have enough calcium to be radio-opaque.
- 50-75% of pigment stones are radio-opaque.
See cards.
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MANAGEMENT
Depends on clinical presentation (above).

Silent Gallstones

Prophylactic Cholecystectomy?
(Silent gallstones)
Prophylactic cholecystectomy is not commonly justified.
80% remain asymptomatic
1-4% will develop complications annually
- skewed like 10% by 5 years and 20% by 20 years.
- these results pretty consistent regardless of population.

Are there predictive factors for which pts will develop problems?
No relationship with pt factors - age sex, comorbidities.
No relationship with gallstone size or nature, wall thickness or GB contractility.
- some studies show stones >2.5cm more likely to get cholecystectomy and GB Ca
- and those <5mm more likely to get pancreatitis.
--> however risk-benefit analysis not clearly in favour of surgery due to still low overall risk.
The development of lap chole should not change this by NIH consensus guidelines.
- conversion rate of 1.6%; morbidity 5%.
Porcelain GB or large polyps (>10-15mm) = more likely to get GB cancer.

Proposed criteria by some authors
- Not evidence-based and can probably be managed expectantly.
Life expectancy >20y
Calculi >2cm
Calculi >3mm and patent cystic duct
Radiopaque calculi
GB polyps >15mm
Porcelain or non-functioning GB
Women <60y
Pts in high-prevalence area for GB Ca

Special Cases

Diabetes
Higher rates of complications and mortality in setting of acute cholecystitis.
But prevalence and natural history roughly same as for non-diabetics
Prophylactic cholecystectomy is not advisable.

Transplantation
Cyclosporine and tacrolimus both predispose.
Evidence in renal transplant does not weigh in favour of cholecystectomy; low rate of occurrence and complications.
Heart transplant = high rates of both; 42% incidence, of these 58& complications within 2 yrs.
- heat & heart lung transplants are treated with USS + prophylactic chole in some centres if +ve
- decision analysis shows less mortality in this group
But not for renal/pancreas transplants.

Hemoglobinopathies
High risk of pigment stones.
Chole. when symptomatic
Prophylactic chole not indicated though, due to higher risk of morbidity.
But consider incidental cholecystectomy if operating for another reason.
- e.g. spherocytosis pts undergoing splenectomy.

Cirrhosis
Similar rate of gallstone progress to non-cirrhotics
- but if cholecystitis, high rate of problems.
High morbidity but lap chole fairly safe in Child A and B
- risks of hematoma, pneumonia and ascites.
- Except if portal hypertension
Bottom line = expectant management.

TPN
Commonly develop gallstones; altered bile and stasis.
High morbidity and mortality
Expectant management and early intervention are the preferred strategies despite old problems.

Bariatrics
Rapid weight loss --> 40% get stones within 6m.
Prophylactic chole is debatable.
- safe but increases procedure length and hospital stay.
Ursodeoxycholic acid (synthetic vile salt) effective in RCTs to prevent stone formation.
- only 2-5% of pts developed stones or needed chole at 6m post op
In absence of firm evidence, concomitant chole is reasonable either pre or intraop when stones present; and ursodeoxycholic acid for 6m.
- except in practice, most do expectant management.

Incidental Cholecystectomy
Some evidence that it is safe and effective in various procedures, eg colorectal, vascular, various.
But in view of complication risk, best don't do it unless a) very good reason and b) very well informed patient.

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