Weatherly's Woes - Pancreas & Bile

GALLSTONES

Cholelithiasis

Bile is made of 4 things. Fats (cholesterol), soaps (bile salts), non-water solubles (unconjugated bili) and water solubles (conjugated bili). Bile is like a chemical soup whose contents are at war with one another. If the concentrations become unbalanced, then stones form. Fat and non-water solubles favor stone formation, while soaps and water-solubles prevent them.

GALLSTONES (cholelithiasis) can be asymptomatic, or they can cause a pattern of abdominal pain called biliary colic. It all begins with cholecystokinin (CCK). CCK is released when you eat fatty foods. When CCK reaches the GB it contracts, forcing the stone into the narrow outlet. The pressure inside the GB rises, and the patient experiences RUQ pain. Since the GB is innervated by a branch of the phrenic nerve, pain can refer to the C3 - C5 region and cause right shoulder pain. Patients with symptomatic gallstones will have a positive Murphy’s sign. The mainstay treatment of all gallbladder pathology is surgical removal of gallbladder (cholecystectomy). Asymptomatic gallstones don’t require surgery. Symptomatic ones warrant an elective GB removal.

The classic patient with cholesterol gallstones has the 4 F’s: female, fourty, fat and fertile. These are all associated with high estrogen.

Pigment stones have a dark color. They’re made up of unconjugated bilirubin. They’re less common.

CHOLECYSTITIS refers to inflammation of the GB. This is a very common complication from gallstones. Inflammation is either ischemic (high pressure crushes own blood supply) or infectious -- whenever fluid stands still, bacteria will infect it. Look for the classic triad of fever, RUQ pain and Murphy’s sign. Diagnose it with an US (thickened wall and surrounding fluid). Cholecystitis is bad because the GB can pop (peritonitis). Antibiotics are controversial. The treatment is an urgent surgical removal (cholecystectomy).

CHOLEDOCOLITHIASIS refers to a gallstone in the common bile duct. In addition to RUQ pain and fever, there is also cholestasis. Cholestasis means that the flow of bile from the liver stops. Conjugated bilirubin builds up in the body, resulting in jaundice. Labwork shows a high Alk Phos. The diagnosis is confirmed with Endoscopic Retrograde Cholangiopancreatography (ERCP). A dye is injected into the base of the biliary tree, the dye flows back up the tree, and then you x-ray it to see if the tree is blocked anywhere. It reminds me a bit of heart caths. ERCP uses a versatile scope tool that allows the operator to remove blockages, stent strictures, etc. Choledocolithiasis is like a dam, and fluid (bile) backs up behind it (cholestasis).

ASCENDING CHOLANGITIS refers to an infected choledocolithiasis. When fluid stands still in the common bile duct, bacteria will eventually infect it. It’s “ascending” because the bacteria will ascend up towards the liver. Patients will have Charcot’s triad (RUQ pain, jaundice, fever). If the infection turns septic, patients get Reynolds Pentad (Charcot’s triad plus confusion and hypotension). The bacteria that cause AC are mostly gut flora (gram negative, lactose-fermenting anaerobic rods) like E coli, Klebsiella, Bacteroides or Enterobacter. A rare, high yield cause is the Chinese Liver Fluke (Clonorchis sinensis), which can be differentiated by the presence of eosinophilia. The fluke is found in raw fish (sushi). The treatment of AC is aimed at fixing the infection (antibiotics) and blockage (endoscopic sphincterotomy with stone extraction). To my knowledge, there is no descending cholangitis.

Sometimes the GB is chronically inflamed. Inflammation results in calcium deposition, which lights up the GB wall on an x-ray, which we call a PORCELAIN GALLBLADDER. Chronic inflammation predisposes to cancer (high GB carcinoma risk). Chronic inflammation is usually due to recurrent gallstones, but a high-yield cause is chronic Salmonella typhi infection, because it hides in the GB while being really quiet (asymptomatic carrier).

GALLSTONE PANCREATITIS refers to when a GB clogs the Ampulla of Vater, thereby obstructing the entire biliary tree. Patients experience acute pancreatitis. Once the pancreatitis has cooled down, GB removal is recommended to prevent a future episode.

ACALCULOUS CHOLECYSTITIS refers to how sometimes in really sick patients, the gallbladder will simply freeze up and die. There is no gallstone. The mechanism probably relates to hypoperfusion. It can be tricky to recognize, because the patient may be intubated or sick with something else serious. But if you manage to notice it in the US, you should put a drain in it and give abx.

A GALLSTONE ILEUS refers to a bowel obstruction caused by a gallstone. How on earth does a gallstone get into the gut? Rarely, a GS gets so large that it disintegrates through the GB and into the small intestine (fistula). The GB and gut can now communicate. Air enters the GB and biliary tree (pneumobilia can be seen on imaging). The stone will enter the gut, and tends to clog the ileocecal valve.

PRIMARY CHOLESTASIS

Ugh

These two diseases are very confusing. They both cause cholestasis (jaundice, pale stools, dark urine, direct hyperbilirubinemia, high alk phos) by damaging the hepatic bile ducts. After a few years, they can both lead to cirrhosis.

Primary Sclerosing Cholangitis is a mysterious condition that causes strictures in the intrahepatic and extrahepatic bile ducts. It begins with scattered inflammation of the ducts, with a characteristic onion skinning histology. That blocks bile flow. Like a dam, fluid swells up behind the blockage, dilating the ducts in a beads-on-a-string pattern. Most patients with PSC also have ulcerative colitis. They typically have elevated p-ANCA which is also seen in UC. PSC can lead to cirrhosis, cholangiocarcinoma and gallbladder cancer.

Primary Biliary Cholangitis is an autoimmune condition that damages the intrahepatic bile ducts. The inflammation is driven by lymphocytes and generates granulomas. PBC is infamous for causing a lot of diffuse itching without a rash, which is due to deposition of bile salts in the skin. The itching with PSC is disabling severe and often gets worse at night. You can replace the itchy bile salts with a less caustic analog (Ursodeoxycholic acid). Labwork will show elevated anti-mitochondrial antibodies. The large majority of patients have some other autoimmune disease. Note - prior to 2014 it was called Primary Biliary Cirrhosis.

ACUTE PANCREATITIS

Pancreatic juice contains a lot of latent digestive enzymes. The enzymes normally awaken in the duodenum. But if the juice is allowed to sit for too long, the enzymes may spontaneously begin to activate (beginning with Trypsin). The enzymes will digest the pancreas (autodigestion). Inflammation, bleeding and fat necrosis ensue. The digestion can spread to the fat surrounding the pancreas, which will release FFAs that bind up calcium (saponification). Hypocalcemia indicates a very severe illness. Most cases are due to alcohol (constricts Sphincter of Oddi) or gallstones (blocks Sphincter of Oddi). There are a ton of rare causes: blunt abdominal trauma, hypercalcemia, hypertriglyceridemia, medications (thiazides, valproic acid), scorpion stings, mumps and posterior duodenal ulcer rupture. On rare occasions, you can see bleeding into the periumbilical area (Cullen’s sign) or flank (Grey Turner sign). Roughly half of patients get a fever. The treatment for pancreatitis is shockingly simple. You don’t let them eat/drink (NPO), keep them hydrated (IV fluids) and give them pain meds as needed. Most patients get better in 2-3 days.

Diagnosing pancreatitis requires 2 out of the 3 of the following:

1. 1. Epigastric pain that radiates to the back.
  2. An elevated lipase level (amylase was the old test, but it’s inferior).
  3. CT scan showing pancreatic inflammation (you don’t have to get a CT scan if the story is classic and the lipase is elevated -- spare them the radiation)

The immediate life threatening complications of pancreatitis include ARDS, DIC and shock. The long term complications include a pancreatic pseudocysts and chronic pancreatitis. The pancreatic pseudocyst is a localized bubble of pancreatic fluid that grows adjacent to the pancreas. It’s walled off by scar tissue. The “pseudo” means that the walls lack epithelium. The bubble is a little leaky, causing lipase to continuously spill into the blood (consider this when the patient’s lipase level remains curiously elevated). The pseudocyst can get infected, so they are usually drained to prevent that.

If you keep getting bouts of Acute Pancreatitis over and over, you can get chronic pancreatitis, where eventually the pancreas becomes so fibrotic that it stops working. Pancreatic insufficiency refers to a pancreas that doesn’t work well. Recurrent attacks can be seen in adults (alcoholics, gallstones) or kids (cystic fibrosis). Without a pancreas, patients can’t make digestive enzymes ( lipase & amylase are NOT elevated), can’t digest fats (steatorrhea & fat soluble vitamin deficiencies) and can’t make insulin (type 1 diabetes). You can identify chronic pancreatitis on a CT scan by lots of bright white spots in the pancreas (dystrophic calcification). As with all chronic inflammatory conditions, there is an increased risk of cancer (pancreatic adenocarcinoma).

Pancreatitis

Pancreatic pseudocyst

Annular Pancreas - congenital malformation where the pancreas improperly rotates during embryology, forming a ring around the duodenum and potentially blocking it.

Pancreas Divisum - the two embryonic halves of the pancreas fail to fuse in utero. There’s a ventral bud and dorsal bud. It’s usually asymptomatic, but it can sometimes cause pancreatitis.

PANCREATIC CANCER

Pancreatic Carcinoma is a cancer of the pancreatic ducts. This is terrible cancer that presents late and has a high mortality. The big risk factors are smoking, chronic pancreatitis and old age. BRCA2, K-RAS and SMAD4 mutations are common. You can track the cancer’s progression using the CA 19-9 marker (but you cannot use it to diagnose). Some patients get a surgical procedure where you remove the head of the pancreas, the duodenum and gallbladder (Whipple procedure).

Cancer in the head of the pancreas classically presents with painless jaundice caused by a blockage of the biliary tree. The gallbladder is often enlarged but not painful (Courvoisier’s sign). Another classic sign is migratory thrombophlebitis (Trousseau syndrome), where lots of painful red dots appear on the limbs.

Cancer in the tail of the pancreas presents with diabetes (destruction of islets of langerhan), Old people don’t get type 1 diabetes out of the blue, especially while losing weight.

The Whipple Procedure