Biliary and Gallbladder conditions

• Cholestasis

  • Any condition that impedes bile flowing freely through the bile ducts.
  • Intrahepatic cholestasis is a failure of bile flow within the liver.
  • Extrahepatic cholestasis is a failure of bile flow beyond the liver.

  Manifestations of Cholestasis

  • Clay-colored stools occur because bile doesn't reach the intestine where it's converted to stercobilinogen, which normally gives feces its typical brown color.
  • Dark urine is caused by an excess of bilirubin in the circulation, excreted through the kidneys.
  • Jaundice and icterus result from the increase in serum bilirubin.

  Management of Pruritus

  • Bile sequestrants (cholestyramine)
  • Rifampicin
  • Oral opiate antagonists (naltrexone and nalmefene) are used as third-line therapy, and can reduce itching.
  • Selective serotonin reuptake inhibitors (sertraline) and gabapentin are used empirically for cholestatic itch, typically in patients with pruritus unresponsive to other agents.

  Cholelithiasis

  • Stones (calculi) form in the gallbladder.
  • It's common in people of northern European descent.
  • 75% of elderly Pima Indians have gallstones.
  • It is more common in women, and the incidence is related to levels of estrogen.
  • Other etiology factors include women on hormone replacement therapy, pregnancy, estrogen birth control pill use, medications that lower serum cholesterol, and obesity.

  Pathophysiology of Cholelithiasis

  • Gallstones are formed from cholesterol, a major component of bile.
  • Stones may be attributed to the calcification of bile pigments.
  • Cholangitis is inflammation of the bile duct, usually attributable to gallstones.
  • Inflammation leads to increased edema.
  • Increased edema can increase the permeability of cell membranes, and predispose the tissue to infection from bacteria from the gut.
  • Ascending cholangitis is infection that moves in the direction of the liver.
  • Suppurative cholangitis is pus produced in the biliary tract due to infection.

  Clinical Manifestations of Cholelithiasis

  • RUQ pain can radiate to the right scapular region.
  • Positive Murphy's sign
  • Anorexia, nausea and vomiting
  • Signs of infection include fever, tachycardia, and hypotension.

  Diagnostic Tests

  • Ultrasound (UTz) is the most useful diagnostic test because it assesses the presence of stones, motility of the stones, and the thickness of the gallbladder wall.
  • Liver function tests (LFTs) are often normal.

  Planning and Implementation

  • The primary methods of treating cholelithiasis are surgery and medication.
  • Nutritional programs with low-fat diets and exercise are also helpful.

  Laparoscopic Cholecystectomy

  • A surgical procedure using laparoscopy to remove the gallbladder, and is the treatment of choice.
  • A small incision is made at the umbilicus plus three other puncture sites.
  • Carbon dioxide may be pumped into the abdominal cavity to help separate the organs.
  • A laparoscope with video camera and laser technology is introduced.
  • The gallbladder is dissected, drained of fluid and stones, and removed through the incision at the umbilicus.
  • Advantages:
    • Faster recovery time
    • Fewer complications
    • Fewer bile duct injuries than open approach
  • Disadvantage: Gallstones can still form in the biliary tree.

  Open Cholecystectomy

  • Performed when the laparoscopic technique fails, there are stones that are inaccessible to the laparoscope, and other surgeries that are required at the same time.
  • The surgeon makes an incision in the RUQ beneath the ribs.
  • The gallbladder is dissected and removed, the cystic duct is ligated, and a T-tube is inserted into the common bile duct to keep it patent.
  • A Jackson-Pratt (JP) tube can be left in at the surgical site to drain fluid from around the area of the gallbladder.

  Pharmacology

  • Nonsurgical treatment takes a long time to dissolve the stones (6-12 months), so it is not popular.
  • Ursodeoxycholic acid (URSO, Ursodiol, or Actigall) can be given alone or in combination with chenodeoxycholic acid (Chenodiol, Chenix, or CDCA).

  Cholecystitis

  • The inflammation of the gallbladder.
  • Causes include:
    • Stones causing irritation and obstruction
    • Bacterial infection
    • Circulatory problems secondary to trauma, tumor impingement, shock, surgery, or dehydration
    • Pancreatitis

  Clinical manifestations:

  • Acute cholecystitis:
    • Pain with abdominal discomfort, which may be referred to the right shoulder.
    • Jaundice is not present because bile flow is not obstructed.
  • Chronic cholecystitis:
    • Fibrosis obstructs bile flow, resulting in cholangitis, pancreatitis, and jaundice.
    • Pruritus occurs due to increased bile salts deposited in the skin.

  Primary Biliary Cholangitis/Primary Biliary Cirrhosis

  • Characterized by inflammation and subsequent destruction of the bile ducts.
  • Incidence:
    • 9 out of 10 cases are middle-aged women.
    • Heredity: More likely to occur in families where one relative has already been diagnosed.

  Pathophysiology

  • The exact mechanism is unknown.
  • Autoimmune factors can cause progressive inflammation.
  • Inflammation causes bile congestion and creates cholestasis.

  Clinical Manifestations

  • Asymptomatic in early stages
  • Increased alkaline phosphatase levels
  • Fatigue and pruritus (most common).
  • Fever, abdominal pain, hepatomegaly, splenomegaly, and hyperpigmentation
  • Jaundice, variceal bleeding, ascites, and encephalopathy

  Diagnostic Tests

  • Increased LFT, especially alkaline phosphatase
  • Positive tests for PT and antimitochondrial antibodies (AMA)
  • Liver biopsy can confirm the diagnosis

  Pharmacology

  • Ursodeoxycholic acid is a naturally occurring bile acid can help to decrease the amounts of other more toxic bile acids.
  • Corticosteroids can decrease autoimmune activity.
  • Cyclosporine is an anti-rejection drug, with side effects including hypertension and kidney dysfunction.
  • Immunosuppressants (Methotrexate, chlorambucil) can cause myelosuppression
  • Colchicine is an anti-gout agent that interferes with WBCs.
  • Cholestyramine (Questran) controls itching.
  • Antiretroviral therapy (Lamivudine, Combivir) is effective in arresting the disease.

  Surgery

  • Cholangiography with balloon dilation of narrowed ducts.
  • Cholecystectomy: Removal of gallstones through sphincterotomy.
  • Liver transplantation is an option for definitive treatment of end-stage disease

  Alternative therapy

  • Silymarin (Liveraid, Livermarin) is an active ingredient in milk thistle (Silybum marianum).
  • Thought to protect the liver and gallbladder from toxic substances.
  • People with allergies to ragweed, marigolds, daisies and other plants of the Asteraceae family should be cautioned.

  Pancreatitis

  • The inflammation of the pancreas, a specialized digestive gland that has both endocrine and exocrine functions.
  • Acute pancreatitis is an acute inflammatory process of the pancreas.
  • It is a mild, reversible condition that can resolve with resting the gut (NPO).

  Etiology

  • Gallstone disease, alcoholism, infections, medications, trauma, obstruction, duodenal diseases and toxins, or genetic diseases that predispose the patient to cholelithiasis.

  Pathophysiology

  • 10-30% of cases are idiopathic
  • Inflammation causes the exocrine enzymes to be prematurely activated, leading to autodigestion of the surrounding tissues and more inflammation, edema, and necrosis.
  • Edema compromises the microcirculation, releasing cytokines such as TNF, interleukin-1, and platelet-activating factor, which contribute to pancreatic damage

  Clinical Manifestations

  • Grey Turner's spots or sign: a bluish flank discoloration due to intravascular damage
  • Cullen's sign: a bluish periumbilical discoloration
  • Abdominal pain radiates to the back, guarding and rebound tenderness, nausea, and vomiting, and abdominal distension.

  Complications

  • Atelectasis, pleural effusion, ARDS, and respiratory failure
  • Cardiovascular problems with hypovolemia, hypotension, and shock
  • Renal failure and coagulation complications
  • Metabolic complications include hypocalcemia/hyperglycemia.
  • GI problems and encephalopathy

  Diagnostic Tests

  • Increased the serum amylase and lipase.
  • Increased ALT, which can be indicative of gallstones.
  • CT scanning is the most useful test for determining the presence of pancreatitis.

  Planning and Implementation

  • Goals of mild acute pancreatitis are to rest the gut, provide supportive care to treat symptoms, identify systemic complications early, and decrease pancreatic inflammation.
  • NPO
  • IVF for proper hydration and electrolyte replacement
  • Pain control

  EBP in Pharmacology

  • Morphine Sulfate potentially causes the sphincter of Oddi to constrict and create more pain.
  • Meperidine (Demerol) converts to the antimetabolite Normeperidine, which can cause seizures and is not a good analgesic choice for pancreatitis pain.
  • Hydromorphone (Dilaudid)

  Management

  • Gastric decompression can relieve nausea, vomiting, and abdominal distension.
  • TPN would be required for prolonged IV interventions
  • Aggressive antibiotic therapy would be used
  • Patient should avoid alcohol.
  • Small, frequent meals

  Chronic Pancreatitis

  • Occurs when there is irreversible damage to the pancreatic acini, ducts, nerves, and islet cells because of continued irritation and injury.

  Epidemiology

  • Men between 30 and 40 are more likely to be affected than women.
  • 70% of all chronic pancreatitis cases are due to chronic alcoholism.
  • The incidence is higher for people with hyperlipidemia and hypertriglyceridemia.

  Predisposing Factors

  • Pancreas divisum is the failure of the pancreatic ducts to fuse during embryonic development, leaving two separate (the dorsal and ventral ducts) to drain the different parts of the pancreas.
  • Cystic fibrosis is the most common cause of pancreatitis among children, caused by protein plugs causing reduced flow of pancreatic enzymes.
  • Big duct chronic pancreatitis indicates a dilation of main pancreatic ducts, and is common in alcoholic pancreatitis.
  • Small duct disease is idiopathic and less responsive to surgical treatment.

  Clinical Manifestations

  • Acute or dull and constant pain referred to the back, and it is worsened with eating.
  • Malabsorption, weight loss, and vitamin deficiency
  • Diabetes mellitus(DM)
  • Decreased duodenal pH = due to reduced secretion of bicarbonate from the pancreatic ducts
  • Osteopenia and osteoporosis

  Diagnostic Tests

  • Serum lipase and amylase are often norma
  • Decreased serum trypsin below 20 mg/dL and presence of steatorrhea are specific for chronic pancreatitis.

  Planning and Implementation

  • Includes Pancreatic enzyme replacement with Pancreatin (Viokase) and Pancrelipase (Cotazym) which contain trypsin, amylase, and lipase, enteric coated to prevent inactivation by stomach acid.
  • Should be given with acid-inhibiting drugs or acid neutralizing drugs to increase stomach pH to increase the efficacy.

  Diet Recommendations

  • Energy requirement: 25 kcal/kg/day
  • Moderate amount of fat (<30% of total energy)
  • High protein (1.2-1.5 g/kg/d)
  • Low carbohydrates (1.2-1.5 g/kg/d)
  • A diabetic diet may be helpful.
  • Abstaining from alcohol is important.

  Pharmacology

  • Pain controlling drugs include Darvocet-N or Tramadol, and Selective serotonin reuptake inhibitors that treat pain and assist with rest.
  • Antidiarrheals: Octreotide (Sandostatin)
  • Antioxidants

  Surgery

  • Ablation (surgical severing [cutting]) of celiac plexus
  • Laparoscopic stenting to keep the ducts open, dilation of strictures, removal of calculi, and drainage of pseudocysts.
  • Whipple procedure (Pancreaticoduodenectomy) entails resection of proximal pancreas, the duodenum, distal portion of the stomach, and distal segment of the common bile duct, followed by an anastomosis of the pancreatic duct, common bile duct, and stomach to the jejunum.

Questions about chronic cholecystitis, Primary Biliary Cholangitis and related treatments like ursodeoxycholic acid, cyclosporine, cholestyramine, and silymarin. Also covers cholangiography and the use of immunosuppressants.