L9: Toxins - Liver

Question 1

Alcoholic liver disease

Answer 1

Direct result of CHRONIC alcohol abuse. The end result of the disease is cirrhosis which culminates in a dysfunctional and diffusely scarred liver

Question 2

Types of alcoholic liver disease

Answer 2

1. Fatty liver
2. Alcoholic hepatitis
3. Cirrhosis

Question 3

Acute effects of alcohol in the CNS

Answer 3

Powerful depressant, inhibitory control centres depressed (excitatory pathways released) in the cortex first then the limbic system (emotions), followed by cerebellum (motor control) and lower brain stem (BP/breathing)

Question 4

Acute effects of alcohol in the liver

Answer 4

Fatty liver - rapid response
Accumulation of small (microvesicular) lipid droplets in hepatocytes
Reversible

Question 5

Acute effects of alcohol in the stomach

Answer 5

Acute gastritis - acute, transient mucosal inflammatory process of the lining of the stomach + haemorrhage and/or sloughing of mucosa

Question 6

Major diseases due to chronic alcohol abuse

Answer 6

Peptic ulcer (stomach)
Abscess (lung)
Tissue remodeling (liver - fatty acid syndrome, cirrhosis, hepatitis)
Cancer (alcohol not a direct carcinogen)

Question 7

Risk factors for serious liver damage in heavy drinkers

Answer 7

Polymorphisms in EtOH-metabolising genes
Obesity
Exposure to other hepatotoxins (high doses of analgesics e.g. paracetamol, antibiotics e.g. penicillin)
Infection with hepatitis C

Question 8

Glisson capsule

Answer 8

The protective covering of the liver

Question 9

Primary cell of the liver and their function

Answer 9

Primary cell - hepatocytes, which are responsible for adjusting secretion and absorption levels of nutrients within the liver and comprise 70-80% of the liver mass

Question 10

True or false: hepatocytes can participate in regenerating damaged hepatic tissue

Answer 10

True

Question 11

Blood enters the lobules of the kidney through a) ___ then flows through small channels called b) ___

Answer 11

a) branches of the portal vein and venules (80%) from the intestine carrying digested food materials and hepatic artery (20%) carrying oxygenated blood from the heart
b) sinusoids

Question 12

The portal vein and venule carry

Answer 12

digested food materials from the intestine

Question 13

Hepatic artery carries

Answer 13

oxygenated blood to the liver and arteriole

Question 14

Most of the alcohol metabolism occurs in the

Answer 14

cytoplasm

Question 15

Mechanism of cytosolic metabolism of ethanol

Answer 15

ADH (alcohol dehydrogenase) converts ethanol to acetyldehyde, one of the most toxic metabolites formed in the body, which is then broken down to acetic acid in the mitochondria.

Question 16

Microsomes

Answer 16

Membrane-bound vesicle enriched on ER in hepatocytes contains CYP2E1/P450 oxidase enzyme system, secondary breakdown system of ethanol when EtOH is high

Question 17

Mechanism of alcohol metabolism in peroxisomes

Answer 17

H2O2 is converted to H2O by catalase

Question 18

Fatty liver - mechanisms of FA metabolism alteration

Answer 18

1. Increase in fatty acids from diet to liver cell in cytoplasm
2. Increased conversion of acetate to FA
3. Increased FA conversion to ketone bodies (subsequent decrease in pH)
4. Increased FA conversion to triglycerides (TG)
5. Decrease in TGs linked to apoproteins (releasing more free FA)
6. Decrease in lipoproteins (more free FA)

Question 19

Fatty Liver

Answer 19

Reversible condition.
Fat accumulation in cells due to increased FA synthesis, production of triglycerides, decreased mitochondrial oxidation of FA, and impaired release of lipoproteins.

Question 20

Key morphologic features of alcohol-induced liver diseases

Answer 20

1. Steatosis/fatty liver - fatty change, perivenular fibrosis. Rapid onset, and reversible with abstinence. Severe prolonged exposure can lead to …
2. Hepatitis - liver cell necroris, inflammation, Mallory bodies, fatty change
3. Repeated attacks and continued exposure can lead to cirrhosis - remodeling due to fibrosis and hyperplastic nodules

Question 21

Pathogenesis and histopathology of alcoholic hepatitis

Answer 21

Visible disruption to sinusoid channels
Infiltration of immune cells e.g. neutrophils
Inflammatory disease cytokines from Kupffer cells (resident macrophages)
Characterised by necrosis of hepatocytes
Cytoplasmic hyaline inclusions (Mallory bodies - intermediate filaments = cytokeratin)

Question 22

Cirrhosis

Answer 22

Necrosis + inflammation + fibrosis + regeneration = cirrhosis
Irreversible scarring leads to portal hypertension

Question 23

Define: sinusoids

Answer 23

Gaps between liver cells

Question 24

Anatomy of liver and blood flow

Answer 24

Blood enters lobules through branches of the portal vein and hepatic artery, then flows through small channels called sinusoids that are lined with primary liver cells (hepatocytes) which remove toxic substances, including alcohol from the blood which then exits the lobule through the central vein/hepatic venule.

Question 25

Clinical liver function assessment tests include testing for which proteins

Answer 25

Alanine aminotransferase
Aspartate aminotransferase
Alkaline phosphatase
Bilirubin - byproduct of Hb breakdown - jaundice
Albumin - produced in liver and major plasma protein
Total protein

Question 26

Pathogenesis of cirrhosis

Answer 26

Fatty liver and/or hepatitis usual precursor but not always
Induction of p450 leads to toxic products and O2 radicals
Microtubular and mitochondrial function affected
Through remodeling and formation of hyaline membranes/Mallory bodies new epitopes can be developed which activate immune response leading to repeated cycles of inflammation-regeneration

Question 27

Hepatic failure occurs when ___ % of hepatic function is lost due to cirrhosis

Answer 27

80-90%

Question 28

Mechanisms that support a protective effect of coffee in liver

Answer 28

Anti-inflammatory activity - inhibition of NFkB, as well as IL-6, TNF-α, IFN-γ and TGF-β
Detoxification - various compounds in coffee induce endogenous Phase II enzyme system

Question 29

Portal hypertension

Answer 29

Elevation of BP within the portal venous system. It develops as a result of the resistance to normal blood flow to the liver via the main portal vein. Portal hypertension is the earliest and most important complication of cirrhosis because most of the physical problems associated with cirrhosis are attributable to it. Leads to gastroesophageal varices, found in 65% of patients with advanced cirrhosis. These are fragile vessels which can rupture and lead to acute haemorrhage and death in about half of patients

Question 30

Hepatic encephalopathy

Answer 30

A brain abnormality caused by the liver’s inability to remove toxins, specifically ammonia, from the blood
Patients can suffer from a wide range of CNS abnormalities that include day-night reversal, mild intellectual impairment, and even coma

Question 31

Alcohol toxicity & pregnancy

Answer 31

Alcohol is able to cross the placenta-foetal
barrier. Brain develops from the third week
Alcohol use in first trimester ‐ morphologic abnormalities, second trimester ‐ spontaneous abortion, third trimester ‐ poor foetal growth

Question 32

Protective effects of moderate drinking

Answer 32

blood vessels - decreases atherosclerosis, decreased AMI
blood - inhibits platelet aggregation, decreased thrombosis
gall bladder - decreased risk of gall stones
bone - decreased osteoporosis

Question 33

Narcosis typically occurs at which concentration of alcohol?

Answer 33

0.1 gm/dl

Question 34

Coma/fatal respiratory arrest typically occurs at which concentration of alcohol?

Answer 34

0.3-0.4 gm/dl

Question 35

Liver contains how many lobes?

Answer 35

3

Question 36

Blood from the liver re-enters circulation via the

Answer 36

hepatic vein