Hepatobiliary physiology & disease (DeMonaco)

Question 1

Liver functions

Answer 1

1. protein synthesis
2. nutrient metabolism
3. immune functions
4. excretion
5. storage

Question 2

Hepatic blood flow

Answer 2

portal vein & hepatic vein & artery

Question 3

Hepatocytes

Answer 3

• make up 60% of liver mass
• metabolic activities (glucose, albumin, cholesterol, BUN, coagulation factors)

Question 4

Cholangiocytes

Answer 4

7-10% of liver mass
- biliary secretions & immune response

Question 5

Kupfer cells

Answer 5

2-5% of liver mass
- phagocytic cells (inflammatory response

Question 6

Stellate cells

Answer 6

3-5% of liver mass
- lipid & vitamin A storage
- produce collagen -> fibrosis

Question 7

Liver and CHOs

Answer 7

Storage & release of glucose
- gluconeogenesis (glucose creation)
- glycogenesis (glycogen storage)
- glycogenolysis (glycogen breakdown into glucose, stimualted by glucagon & inhibited by insulin)

glycogen storage/glycogenesis can occur in liver & skeletal muscle

glucagon = peptide hormone synthesized by alpha cells of pancreatic islets of Langerhans in response to low blood sugar

Question 8

Protein metabolism in the liver

Answer 8

• Ammonia = by-product of protein metabolism that gets transformed/detoxified into urea by the liver -> see decreased urea in liver dysfunction/failure

urea eventually gets transformed into ureic acid then excreted in urine

Question 9

Lipid processing in the liver

Answer 9

• In duodenal lumen, bile salts break down fats -> enter into enterocytes, transforemd into chylomicrons -> transported to lymphatics via lacteals -> enter circulation thru subclavian vein via thoracic duct -> heart -> aorta -> celiac a. -> hepatic a. -> liver for further processing:
• liver makes triglycerides, cholesterol, lipoproteins (VLDL, LDL, HDL); performs beta oxidation of fatty acids to create ketones for energy (anaerobic glycolysis)
• Clinical scenarios: DKA, hepatic lipidosis; hypocholesterolemia (liver failure)

Question 10

Albumin

Answer 10

• synthesized in the liver
• functions: transports hormones, FA; maintains oncotic pressure
• hypoalbuminemia: cavitary effusions & edema

Question 11

Evidence of liver dysfunction/failure:

Answer 11

1. Coagulopathies (decr. production of clotting factors)
2. Hypoalbuminemia (edema, cavitary effusions)
3. Hypoglycemia, Hypocholesterolemia
4. Iron deficiency (liver makes transport and storage proteins for iron transport/storage – transferrin/ferritin)
5. Cholestasis (intra or extrahepatic)
6. Septicemia (failure of liver to process/clear out enteric organisms from entering hepatic vein/systemic circ.)
7. Toxicity (failure of liver to detoxify xenobiotics/other toxins into less lipophilic metabolites to bet excreted in bile or urine for elimination)
8. Decreased urea // ammonia toxicity
9. Jaundice/Icterus (Hepatic – failure of metabolism of bilirubin from unconjugated to conjugated; Post-Hepatic – decr. excretion, cholestasis)

Pre-hepatic hyperbilirubinemia usually due to RBC instability

Cholestasis will lead to a lack of bile acid in SI to absorb fat-soluble vitamins like VitK)

Question 12

Describe the 3 jaundice classifications

Answer 12

1. Prehepatic: Overproduction of unconnjugated bilirubin -> excess RBC lysis -> impaired uptake of bilirubin by the liver
2. Hepatic: failureof liver to conjugate bilirubin -> excess unconjugated bilirubin
3. Posthepatic: decreased excretion of conjugated bilirubin (intra or extrahepatic obstruction – bile duct obstruction)

unconjugated = indirect, conjugated = direct

Question 13

Copper hepatopathies

Answer 13

Normal animal: liver absorbs takes up any dietary copper in the SI thru portal circulation, and then utilizes it for its own function, transports to other tissues for use, or excretes it

Copper hepatopathies: Copper builds up -> toxic to hepatocytes elevated liver enzymes-> liver damage/disease

Question 14

Describe the hepatobiliary system with regards to order of bile flow

Answer 14

Hepatocytes produce bile -> bile flows down canaliculi -> bile ductules -> intralobular ducts -> interlobular ducts -> hepatic ducts -> into gallbladder via cystic duct for storage

Food digestion: gallbladder stimulated to contract by CCK release -> bile flows back out and down into common bile duct, spincter of oddi relaxes, and bile flows out, through major duodenal papilla and into duodenum

Bile acids test: feed animal either a fatty meal or a drug that can induce GB contractions (erythromycin)

Question 15

Bile modification in the gallbladder

Answer 15

Hepatic bile becomes concentrated 10-to-15 fold in the gallbladder via absorption & secretion of water and electrolytes -> concentrated bile can aid in digestion/absorption of fats

Question 16

What causes gallbladder dysfunction?

Answer 16

Dysmotility
- impaired smooth muscle contractility (inflammation, steroidhormones increased bile cholesterol concentration, CCK receptor dysfunction)
- ineffective expulsion (stasis caused by mucoceles, obstruction)

Question 17

Where do bile acids get reabsorbed?

Answer 17

In the distal ileum via enterohepatic circulation (90% first-pass hepatic extraction, < 5% in fecal losses)

Question 18

Acute Hepatobiliary Disease

Answer 18

• sudden onset of clinical signs (issues have been occurring past1-2 months)
• clinical signs are typically more severe than in chronic disease

Question 19

Differentiating between Acute Liver Injury and Acute Liver Failure

Answer 19

ALI
- hepatocellular damage/necrosis
- retain heaptic function

ALF
- decreased hepatic function (sudden loss of > 70% of hepatic functional mass)

Question 20

Chemistry signs of hepatobiliary disease

Answer 20

• Elevated hepatic enzymes (degree & pattern)
• Decreased albumin, cholesterol, glucose, BUN (not all need to be decreased)

Question 21

How to differentiate cholestatic versus hepatocellular disease on chemistry

Answer 21

• Cholestasis: ALP > ALT (+/- hyperbilirubinemia)
• Hepatocellular: ALT > ALP (+/- hyperbilirubinemia)

ALP = alk phos

Question 22

Leptospirosis

Answer 22

Infectious disease that can cause acute liver injury
- AKI with or without elevated hepatic enzymes (hepatocellular or cholestasis)

Question 23

Common toxins that can cause acute hepatic injury

Answer 23

• xylitol
• amanita mushroom
• Sago palms, blue green algae, aflatoxins

Question 24

Common drugs that can cause acute heaptic injury or cholestasis

Answer 24