L8 - Liver Disease

Question 1

Where is liver located?

Answer 1

• It is located beneath the diaphragm in the right upper
quadrant of the abdomen and is protected by the ribs.
• Divided into left and right anatomic lobes by the
falciform ligament, an anterior extension of the
peritoneal folds that connects the liver to the diaphragm
and the anterior abdominal wall.

Question 2

Liver anatomy?

Answer 2

Hepatic vein
• blood returning to heart
Hepatic artery
• bringing fresh blood from heart
Portal vein
• bringing blood from intestines
Bile duct
• bile draining to intestines

Question 3

Liver blood supply?

Answer 3

Receives ~ 1500 ml of blood per/min; ~25% of the cardiac output. The liver has a dual blood supply:
1. Hepatic artery , a branch of the celiac axis, provides oxygen-enriched arterial blood.
2. Portal vein , which carries blood from the spleen and nutrient enriched blood from the GI tract, supplies ~ 70% of the blood supply
**check slide (7/47)

Question 4

Venous drainage from the liver?

Answer 4

Venous drainage from the liver ultimately converges into the right and left hepatic veins, which exit on the posterior surface of the liver and join the inferior vena cava near its entry into the right atrium.

Question 5

Liver organization models?

Answer 5

Anatomical model - the liver lobule
Functional model - the liver acinus

Question 6

The liver acinus zones: Zone 1?

Answer 6

Zone 1:
• Rich with lysosomes and mitochondria
• Oxygen rich
• Least susceptible to hypoxia/necrosis
• Highest degree of metabolic activity
• Provides base for hepatic regeneration

Question 7

The liver acinus zones: Zone 2?

Answer 7

Zone 2: intermediate.
• Contains primarily
hepatocytes, site of
metabolic action

Question 8

The liver acinus zones: Zone 3?

Answer 8

Zone 3:
• Enriched with endoplasmic reticulum
• Low oxygen tension
• Susceptible to hemodynamic stressors
• Primary site for drug detoxification (phase I and II metabolism)

Question 9

Liver cellular architecture?

Answer 9

**Check slides (12/47)

Question 10

Liver cellular architecture: Hepatocytes

Answer 10

70% of liver mass. Functional cells of the liver.
Site of metabolic and synthetic functions; divide
under stress and cytokine activation.

Question 11

Liver cellular architecture: Kupffer cells

Answer 11

Specialized, self
renewing, long lived
macrophages that line the walls of the
sinusoids that form part of the reticulo
endothelial system. Part of innate immune
system (non specific targeting of foreign
antigens & antigen antibody complexes)

Question 12

Liver cellular architecture: Stellate cells=Ito cells

Answer 12

Between hepatocytes and endothelial cells; store
fat soluble vitamins (quiescent); contractile
properties, involved in regulating blood flow;
synthesize collagen during fibrosis (stimulated)

Question 13

Liver cellular architecture: Hepatic endothelial cells

Answer 13

Fenestrated cells that line sinusoids. Play role in
regulating intrahepatic resistance to blood flow via
NO (vasodilator).

Question 14

Liver cellular architecture: Dendritic Cells

Answer 14

Localized around central vein; play an immune role
in antigen presentation and activation of T
lymphocytes.

Question 15

4 main physiologic functions of the liver?

Answer 15

Metabolism
Synthesis
Excretion
Storage

Question 16

Metabolic function of the liver?

Answer 16

Carbohydrate metabolism
• e.g. Glycogenolysis and gluconeogenesis
Protein metabolism
• e.g. Protein catabolism into amino acids
Lipid metabolism
• E.g. Free fatty acid metabolism
Xenobiotic metabolism and excretion

Question 17

Synthetic function of the liver?

Answer 17

Serum protein synthesis
• E.g. albumin, alpha 1 antitrypsin, hormone binding proteins
• Immunoglobulin synthesis does NOT occur in the liver
Coagulation factor synthesis
• E.g. fibrinogen, prothrombin, clotting factors and antithrombin
Lipid synthesis
• E.g. cholesterol, apolipoproteins, triglycerides

Question 18

Excretory and secretory function of the liver

Answer 18

• Organic compounds extracted from sinusoidal blood, bio-transformed, & excreted into bile/urine.
• Secretion of bilirubin
• Secretion of bile acids
• Clearance of hormones, drugs, activated clotting factors from portal circulation.
** Check slide (19/47 -> 25/47)

Question 19

Liver pathology?

Answer 19

A number of mechanisms can lead to liver disease:
• Infections; eg. Viral hepatitis
• Toxins; eg. Alcoholic hepatitis, medications
• Genetic; eg. Hemochromatosis, Gilbert’s syndrome
• Immune; eg. Autoimmune hepatitis, Primary Biliary cirrhosis
• Neoplastic; eg. Hepatocellular carcinoma

Question 20

Cirrhosis?

Answer 20

• End stage consequence of liver injury
• End stage of scar formation due to
(1) chronic hepatitis OR
(2) chronic cholestasis
WHO definition
•“Diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules.”

Question 21

Mechanisms of Liver Pathology:
Fibrosis and Cirrhosis

Answer 21

Acute and chronic liver injury lead to
1. Cell death induced loss of
hepatocytes
2. Proliferation of stellate cells
3. Liver fibrosis
**Check slide (27,28/47)

Question 22

Consequences of Cirrhosis?

Answer 22

1. Portal hypertension
2. Decreased hepatic function:
   • synthetic/excretory
   • metabolic/catabolic
   • detoxification
3. Liver failure
   • Lab features
   • ↓liver protein production
   ↓Albumin
   • ↑Prothrombin Time (PT)
   • AST/ALT>1
   • ↓platelets
   • ↑Total bilirubin (late finding)

Question 23

Laboratory assessment of liver injury and function?

Answer 23

Liver injury tests:
• Liver enzymes
Liver function tests:
• Surrogates for excretion (bilirubin)
• Metabolism (ammonia)
• Synthesis (albumin, prothrombin time)

Question 24

Liver enzymes allow assessment of liver injury?

Answer 24

**Check slide (31/47)

Question 25

Hepatocellular Injury?

Answer 25

AST/ALT Ratio is normally ~ 1 •↑ in AST and ALT levels, but ratio is still ~ 1 -\> Acute injury AST\>ALT -\> Alcoholic Hepatitis or Chronic Liver Disease • Alcohol induces release of mitochondrial AST w/o visible cell damage • Chronic injury also decreases production of ALT

Question 26

Biliary Tract Injury?

Answer 26

ALP and GGT are used to assess Biliary tract •↑ ALP -\> Biliary tract injury/cholestasis • Associated with biliary duct obstruction, 1’ biliary cirrhosis, biliary atresia • Cholestasis stimulates synthesis of ALP by hepatocytes. •↑ GGT -\> Biliary tract injury/cholestasis • NOTE: GGT is also elevated in acute hepatitis.

Question 27

Bilirubin?

Answer 27

The type of bilirubin present provides additional information: - Increase in Unconjugated Bilirubin: • Hemolysis • Inability of hepatocytes to take up bilirubin from blood • Conjugation is impaired - Increase in Conjugated Bilirubin: • Inability of hepatocytes to secrete conjugated bilirubin • Biliary tract obstruction \*\*Check slide (35,36/47)

Question 28

Summary of lab tests

Answer 28

• Predominant elevation of ALT and AST suggests parenchymal liver injury or hepatitis. • Predominant elevation of biliary enzymes ( ALP and GGT) suggest bile duct injury, cholestasis, or cholangitis. • Elevation of bilirubin suggests cholestasis. Obstruction of the biliary tree should be excluded as a cause of hyperbilirubinemia. • Hepatic synthetic function is assessed by measuring albumin and clotting (prothrombin time)

Question 29

Biliary atresia?

Answer 29

bile flow from the liver to the gallbladder is blocked. This causes the bile to be trapped inside the liver, quickly causing damage and scarring of the liver cells (cirrhosis), and eventually liver failure.

Question 30

Cholestasis?

Answer 30

bile cannot flow from the liver to the duodenum. The two basic distinctions are: - an obstructive type of cholestasis where there is a mechanical blockage in the duct system that can occur from a gallstone or malignancy, - and metabolic types which are disturbances in bile formation that can occur because of genetic defects or acquired as a side effect of many medications

Question 31

Portal hypertension?

Answer 31

an increase in the blood pressure within the portal venous system.

Question 32

Cholangitis?

Answer 32

is an inflammation of the bile duct system that is usually related to a bacterial infection.