Liver disorders and Gallstones (Zana)

Question 1

2 forms of cholestasis

Answer 1

intra and extrahepatic

Question 2

what is the reason for intrahepatic cholestasis

Answer 2

bile secretion from the hepatocytes into the canaliculi is impaired

Question 3

diseases/conditions leading to intrahepatic cholestasis

Answer 3

1. viral hepatitis
2. drugs such as chlorpromazine or toxins such as alcohol
3. inflammation of the biliary tract (cholangitis)
4. auto immune disease (primary biliary cirrhosis)
5. cystic fibrosis

Question 3

diseases/conditions leading to intrahepatic cholestasis

Answer 3

1. viral hepatitis
2. drugs such as chlorpromazine or toxins such as alcohol
3. inflammation of the biliary tract (cholangitis)
4. auto immune disease (primary biliary cirrhosis)
5. cystic fibrosis

Question 4

why does extrahepatic cholestasis occur?

Answer 4

due to obstruction to the flow of bile through the biliary tract by:
- biliary stones
- inflammation of the biliary tract
- pressure on the tract from the outside by malignant tissue, usually the head of the pancreas
- biliary atresia

Question 5

if only part of the biliary system is involved by intrahepatic lesions such as cholangitis, early primary biliary cirrhosis or primary or secondary tumours, bilirubin concentrations will be __________

Answer 5

normal, as long as unaffected areas secrete bilirubin

Question 6

sensitive test for cholestasis

Answer 6

alkaline phosphatase activity

Question 7

if we have increased ALP, next step is…

Answer 7

to prove that this ALP is from hepatic origin

Question 8

Patients with prolonged and more widespread cholestasis may present with

Answer 8

severe jaundice and pruritus due to deposition o retained bile salts in the skin (plasma bilirubin may be >800 umol/L)

Question 9

Dark urine and pale stools suggest

Answer 9

biliary retention of conjugated bilirubin

Question 10

Cholesterol retention may cause

Answer 10

hypercholesterolaemia

Question 11

The jaundice caused by extrahepatic obstruction due to malignant tissue is typically

Answer 11

painless and progressive

Question 12

intraluminal obstruction by a gallstone may cause

Answer 12

severe pain, which, like the jaundice, is often intermittent

Question 13

If a large stone lodges in the lower end of the common bile duct, the picture may be indistinguishable from

Answer 13

from that of malignant obstruction.

Question 14

Unless the cause is clinically obvious, evidence of dilated ducts due to extrahepatic obstruction should be sought using tests such as

Answer 14

ultrasound, computerized tomography (CT) scanning or cholangiography

Question 15

AST and ALT half life

Answer 15

AST 17h
ALT 36h

Question 16

Causes of elevated liver enzymes (5)

Answer 16

1. VIRAL HEPATITIS
   -Hepatitis A/B/C/E, EBV, CMV
   -AST>ALT-early phase
   -ALT>AST-later phase
2. HEPATOBILARY OBSTRUCTION
   2-8 increase of normal
3. CHRONIC HEPATITIS
4. BILIARY CIRRHOSIS
   4 times increased as normal
5. OTHER-toxins, drugs, alcohol, fatty liver disease, autimmune disorders, matabolic

Question 17

how do we know that ALP increase is from hepatic origin

Answer 17

Alkaline phosphatase is derived from a number of different tissues, including the liver, the osteoblasts in bone and the placenta

A raised ALP concentration in the presence of a raised g-glutamyl transferase (GGT) concentration implies that the ALP is of hepatic origin.

Question 18

Which 2 out of 4 bile acids are produced in the liver

Answer 18

cholic acid and chenodeoxycholic acid, are synthesized in the liver from cholesterol and are called primary bile acids.

Question 19

explain secretion of bile salts

Answer 19

They are secreted in bile as sodium salts, conjugated with the amino acid glycine or taurine (primary bile salts).

These are converted by bacteria within the intestinal lumen to the secondary bile salts, deoxycholate and lithocholate.

Secondary bile salts are partly absorbed from the terminal ileum and colon and are re-excreted by the liver (enterohepatic circulation of bile salts). Therefore, bile contains a mixture of primary and secondary bile salts.

Deficiency of bile salts in the intestinal lumen leads to impaired micelle formation and malabsorption of fat

Question 20

what is contained within hepatic bile

Answer 20

bilirubin, bile salts, phospholipids, cholesterol, electrolytes, small amount of protein

Question 21

difference between hepatic and gall bladder bile

Answer 21

In the gall bladder there is active reabsorption of sodium, chloride and bicarbonate, together with an isosmotic amount of water.

Consequently, gall bladder bile is 10 times more concentrated than hepatic bile; sodium is the major cation and bile salts the major anions.

The concentrations of other non-absorbable molecules, such as conjugated bilirubin, cholesterol and phospholipids, also increase.

Question 22

how do gallstones differ from renal calculi

Answer 22

Only about 10 per cent contain enough calcium to be radio-opaque

Question 23

what type of gallstones we have

Answer 23

pigment stones
cholesterol stones
mixed stones

Question 24

describe pigment stones

Answer 24

Pigment stones are found in such chronic haemolytic states as hereditary spherocytosis. Increased breakdown of haemoglobin increases bilirubin formation and therefore biliary secretion. The stones consist mostly of bile pigments, with variable amounts of calcium. They are small, hard and dark green or black, and are usually multiple. Rarely, they contain enough calcium to be radio-opaque.

Question 25

Describe cholesterol stones

Answer 25

Cholesterol is most likely to precipitate if bile is supersaturated with it; further precipitation on a nucleus of crystals causes progressive enlargement. Not all patients with a high biliary cholesterol concentration suffer from bile stones. Changes in the relative concentrations of different bile salts may favour precipitation. The stones may be single or multiple. They are described as mulberry-like and are either white or yellowish; the cut surface appears crystalline. There is no clear association between hypercholesterolaemia and the formation of cholesterol gallstones, although both may be more common in obese individuals. However, there may be an increased incidence in patients taking some lipid-lowering drugs, such as the fibric acid derivatives.

Question 26

association between hypercholesterolemia, lipid lowering drugs and cholesterol gallstones

Answer 26

There is no clear association between hypercholesterolaemia and the formation of cholesterol gallstones, although both may be more common in obese individuals. However, there may be an increased incidence in patients taking some lipid-lowering drugs, such as the fibric acid derivatives.

Question 27

describe mixed stones

Answer 27

Most gallstones contain a mixture of bile constituents, usually with a cholesterol nucleus as a starting point. They are multiple-faceted, dark-brown stones with a hard shell and a softer centre and may contain enough calcium to be radio-opaque.

Question 28

what are the consequences of gallstones

Answer 28

1. biliary colic 2. acute cholecystits 3. chronic cholecystitis 4. obstruction of the common bile duct 5. gallstone ileus or carcinoma of gall bladder

Question 29

what labs to order to investigate suspected liver disease

Answer 29

● bilirubin – excretory function, ● aminotransferases (ALT and/or AST) – hepatocellular damage, ● alkaline phosphatase – cholestasis, ● albumin and/or prothrombin time – synthetic function, ● g-glutamyl transferase – enzyme induction, cholestasis or hepatocellular damage.