Module 2: Chapter 4 and 5

Question 1

Types of Gallstones

Answer 1

White: cholesterol stones. Occurs when supersaturated bile undergoes nucleation and their growth is promoted by gallbladder stasis Black: hemolysis causes bilirubin which makes it black brown: stones form due to infection

Question 2

risks for cholesterol gallstones

Answer 2

7 Fs: female, fertile (pregnancy), fifty (over the age of 50), family (history, Indians > hispanics> caucasians), fat, fasting (rapid weightless can precipitate gall stones), pharmacology (drugs like estrogen, octreotide, ceftriaxone

Question 3

4 big complications of gallstones

Answer 3

1. biliary colic 2. acute cholecystitis: occurs when a stone is lodged in the neck of the gallbladder and the gallbladder becomes inflamed and infected. They will present with fever, RUQ pain, Murphy’s sign on physical or ultrasound exam (where the patient stopsinspiration when inflamed gallbladder hits your hand or the US probe), and a high WBC but liver tests are usually normal (or mildly elevated by sepsis). Treatment is with antibiotics and cholecystectomy 3. Cholangitis: when a stone obstructs the common bile duct. presents with fewer, RUQ pain, jaundice, elevated liver tests and can be septic. Require antibiotics and ERCP to relieve the obstruction 4. pancreatitis: occurs when a stone passes through or obstructs the pancreatic duct, which joins the common bile duct at the ampulla of Vater. Patient will present with epigastric pain that radiates into the back, nausea, vomiting, and may have fever, low blood pressure and tachycardia. They will have an elevated lipase and may have elevated liver tests and bilirubin. Treatment is with narcotics, IV fluids, and bowel rest (nothing per oral or NPO) although early feeding may improve outcomes. They may need ERCP for stone removal and subsequent cholecystectomy.

Question 4

benign stricture of ducts causes

Answer 4

5Is inflammatory iatrogenic (caused by cholecystectomy) ischemic: with hepatic artery thrombosis after liver transplant or after chemotherapy infection: flukes idiopathic

Question 5

malignant strictures

Answer 5

cholangiocarcinoma cancer in the head of the pancreas, ampulla of Vater, or a second part of the duodenum.

Question 6

classifications of cholangiocarcinoma

Answer 6

o Intrahepatic (iCCA – #1) o Perihilar (pCCA – #2) previously known as Klatskin tumours o Distal (dCCA – #3)

Question 7

Management of different cholangiocarcinoma classifications

Answer 7

iCCA can under resection, ablation, chemoembolization or chemotherapy pCCA: partial hepatectomy, and in highly selected cases are candidates for liver transplantation however, many cases can only be palliated with PTC and stenting with or without chemotherapy dCCA may be able to undergo resection (Whipple’s) or can be palliated with ERCP or PTC and stenting with or without chemotherapy

Question 8

Presentation and maangement of pancreatic cancer

Answer 8

If at the head: often don’t feel it, jaundice

If at the body of tail: weight loss, back pain, depression

Management: Prognosis is quite poor
o Only resectable if it is not involving the veins and arteries
o If in the head of the pancreas, surgery requires a Whipple’s operation (see above)
o Chemotherapy for advanced cases

o Palliation may require stenting, surgical bypass of obstructed duodenum or bile duct with or
without celiac plexus block for pain control

Question 9

Immune Causes of Cholestatic Liver disease

Answer 9

PBC, PSC, GVHD, transplant rejection

Question 10

Inflammatory causes of cholestatic liver disease

Answer 10

Alcohol, drug induced liver injury, sarcoidosis

Question 11

Infection causes of cholestatic liver disease

Answer 11

hepatitis (Can have a cholestatic phase during resolution of an acute hepatitis), CMV

Question 12

Sepsis causes of cholestatic liver disease

Answer 12

the most common cause of cholestatis in hospitalized patiens

• liver biospy shows cholangitis lenta

Question 13

Infiltrative causes of cholestatic liver disease

Answer 13

amyloidosis

granulomatous heaptitis

malignancy

Question 14

congential causes of cholestatic liver disease

Answer 14

Progressive Familial Intrahepatic Cholestasis PFIC

Question 15

Pregnancy causes of cholestatic liver disease

Answer 15

Intrahepatic Cholestasis of Pregnancy (ICP)

Occur in up to 1.5% of pregnancies (more common with twins) Presents with intense pruritus, ALT > ALP and serum bile acids, in the 3rd trimester

Mutations in MRD3 can be seen 15%

risk of premature labour and risk of stillbirths

Moms should receive ursodeoxycholic acid (UDCA) and cholestyramine

Vitamin K is given before delivery to reduce bleeding complications

It recurs in >50% of subsequent pregnancies

Question 16

biopsy/histology features of cholestasis

Answer 16

feathery degeneration of hepatocytes

accumulation of bile with hepatocytes

bile pluge in bile ducts

Question 17

Granulomatous Hepatotis causes

Answer 17

infections: TB, syphillis, CMV

Drugs, sulfonamids, allopurinol

Immune: PBC, sarcoidosis

Malignancy: Hodgkins lymphoma

Idiopathic

Question 18

Signs and Symptoms of Cholestasis

how would you manage these symptoms?

Answer 18

Pruritis, fatigue, dark urine, pale stools (no milirubin), RUQ pain, fever, weightloss. You’d see ADEK vitamine deficincies (night blindness, metabolic bone disease, neurological symptoms, bleeding and icnreased INR)

• therefore, you’d see excoriations, hyperpigmentation, xanthoma, xantholasma

_Metabolic bone disease_ can develop even in the absence of vitamin D deficiency
o Osteopenia (thin bones), osteoporosis (brittle bones with bone density \< 2.5 standard dev. Managed with calcium, vitamin D supplementation and bisphosphonates (bone building
medications) or parathyroid hormone

Pruritus management

o Pruritus can be one of the most troubling symptoms
o First line agents include sedating antihistamines (take at bedtime as they cause drowsiness)
and cholestyramine which binds the pruritogen (component of bile that causes itching) so that it is passed in the stool instead of undergoing enterohepatic circulation
o Second line agents include rifampin (antibiotic which upregulate enzymes in the liver that
metabolize the pruritogen), naloxone or naltrexone (narcotic reversal agents which blocks the increased opioid tone associated with chronic cholestasis), sertraline (Zoloft® an anti- depressant which is a selective serotonin reuptake inhibitor)
o Third line therapies include plasmapheresis and ultimately liver transplantatio

Fatigue management

• can be severe (similar to patients with multiple sclerosis) and treatment is difficult.
• must rule out depression, sleep disturbance and hypothyroidism
• regular exercise helps
• you can use low doses of anti-depressants even in the absense of depression`

Question 19

Clinical features, Diagnosing, Lab tests, treatment of Primary Biliary Cholangitis

Answer 19

Clinical featuers: sicca syndrome (dry eyes and mouth), metabolic bone disease, cirrhotic (not all the time), could develop Hepatocellular carcinoma. Could have portal hypertension.

Diagnosis and Tests

• dx through increased ALP (cholestasiss), no etOH or other liver diseases
• test with AMA. It’s diagnostic. Can do immunoblot for PDC if you suspect PBC but AMA is neg. May have high cholesterol and igM.
• liver biopsy not needed, but should be done if you suspect PBC and AMA is negative. Features would overlap with AIH such as high ALT, increased igG, and positive ANA/ASMA
• would see a florid duct lesion.
• stages 1-4, and not all patients will have cirrrhosis.

Treatement: UDCA 13-15mg/kg to normalize ALP. Minimal impact on fatigue and priritus though.

If non responsive to UDCA, use a second line therapy like OCA or bezafibrate or budesonie (corticosteroid) with high first pass metabolsim, but still can have steroid relate side effects.

Question 20

What autoimmune cholestasis is associated with IBD

Answer 20

PSC

Question 21

What diseases are associated with PSC

Answer 21

IBD, and those with PSC have a high chance of getting ulcerative colitis of Crohn’s Disease. Affects Males more.

Question 22

Which autoimmune cholstasis disease affects woemn more?males?

Answer 22

Women: older, PBC

males: younger, psc

Question 23

pathophysiology of PSC

Answer 23

Cause is unknown
o Genetically susceptible host = half of identified genes are also associated with IBD and half
are associated with other autoimmune diseases

o Environmental factors = association with colitis, toxic bile acids, recurrent infections,
ischemia to bile ducts

o Dysregulated immune system = T cells from the 7 integrin
track to the liver where MADCAM1 is expressed on endothelium

Question 24

Diagnosing PSC and Clinical Features

Answer 24

Diagnosing:

• ALP is elecated (cholestatic elevated liver test)
• ANA and ASMA positive
• exclude igG4, may see ANCA autoantibodies
• MRCP shows chain of lakes

Liver biopsy if MRCP is normal OR you think this person has PSC with AIH. o Liver biopsy is performed if MRCP is normal (to look for small duct PSC) or if suspicious for
overlap with autoimmune hepatitis (AIH-PSC overlap frequent in children)
Classic finding is “onion-skin fibrosis” around the bile duct (see above), which is
pathognomonic but is only present in one-third of biopsies

Clinical Features

• can be asymptomatic, but pruritis, fatigue and metabolic bone disease are common. Can progress to cirrhosis with liver failure. PsC patients often have a specific phenotype of IBD.

o They have a higher risk of malignancies
50% risk of colorectal neoplasia at 25 years (versus 10% if colitis without PSC)
10% lifetime risk of cholangiocarcinoma (CCA) [see Chapter 13.2]
Higher risk of gallbladder cancer, so patients should have yearly ultrasounds, and if GB
polyps found they should undergo cholecystectomy

Question 25

Treatment of PSC

Answer 25

o Asymptomatic patients have decreased survival compared to healthy controls
o If symptomatic, median survival (without liver transplant) is approximately 8 - 10 years
o Prognosis of cholangiocarcinoma is very poor

There is no effective medical therapy for PSC and liver transplant is the only lifesaving therapy4

Question 26

what tool is used to screen for PSC

Answer 26

ANA and ASMA, then MRCP