The document summarizes the different types of liver injury and conditions that can result from toxic effects on the liver. It discusses how chemicals can cause hepatocellular degeneration through damaging mitochondria, plasma membranes, the endoplasmic reticulum, or nucleus of liver cells. This can lead to fibrosis, cirrhosis, or liver tumors over time. Other toxic effects include cholestasis (decreased bile flow), sinusoidal damage, peliosis hepatis (blood-filled cysts), and fatty liver caused by lipid accumulation within liver cells. The document provides examples of chemicals that can induce each type of toxic liver effect.

1. HEPATOTOXICITY: TOXIC
EFFECTS ON THE LIVER
By Prandeep Borah

4. FUNCTIONS
(1) Filtration
(2) carbohydrate storage and metabolism;
(3) metabolism of hormones, endogenous wastes, and
foreign chemicals;
(4) synthesis of blood proteins;
(5) urea formation;
(6) metabolism of fats; and
(7) bile formation

9. TYPES OF TOXIN INDUCED LIVER INJURY:
 Hepatocellular Degeneration and Death-
1. Mitochondria. These organelles are important for
energy metabolism and synthesis of ATP.
-> Release calcium/ maintain homeostasis
->lose the ability to regulate solute and water balance,
and undergo swelling.
-> chemicals- carbon tetrachloride, cocaine,
dichloroethylene etc.

10. 2. Plasma Membrane- Important in maintaining the ion
balance between the cytoplasm and the external
environment.
-> Loss of ionic control can cause a net movement of water
into the cell, resulting in cell swelling.
->chemicals- acetaminophen, ethanol etc.
3. Endoplasmic Reticulum- Responsible for synthesis of
proteins and phospholipids in the hepatocyte.
->Principal site of biotransformation of foreign
chemicals;maintain Ca homeostasis.
->chemicals- acetaminophen, bromobenzene, carbon
tetrachloride, and cocaine.

11. 4. Nucleus-
->Some chemicals or their metabolites can bind to DNA,
producing mutations > leading to cell death.
->Some chemicals appear to cause activation of
endonucleases, enzymes located in the nucleus that
digest chromatin material >leads to uncontrolled
digestion of the cell’s DNA.
->chemicals- aflatoxin B, beryllium, Ethionine etc.

12.  5. Lysosomes- These subcellular structures contain
digestive enzymes (e.g., proteases) and are important in
degrading damaged or aging cellular constituents
-> In hepatocytes injured by chemical toxicants, their
numbers and size are often increased.

13. FIBROSIS & CIRRHOSIS
 Hepatic fibrosis (scaring) occurs by the accumulation of
excessive amounts of fibrous tissue, specifically fibril
forming collagens type I and III.
> central veins, portal tracts, disse
>With continuing collagen deposition,
>fibrous scars.
> nodular regeneration of hepatocytes leads fibrosis to
progress to cirrhosis
* Blood flow through the liver becomes obstructed,
leading to portal hypertension, internal hemorrhage.
* Chemicals involves ethanol, carbon tetrachloride,
trinitrotoluene.

16. LIVER TUMORS
Chemicals can induce neoplasia which leads
to tumors . Etiology :-
• Hepatitis B
• Hepatitis C
• Cirrhosis
- 70% of HCC arise on top of cirrhosis
• Toxins -Alcohol -Tobacco - Aflatoxins
• Autoimmune hepatitis
• States of insulin resistance- Overweight in males
Diabetes mellitus

17. CLASSIFICATION
Malignant
>hepatocellular
carcinomas:-derived
from hepatocytes,
>cholangiocarcinomas:
-from bile duct cells,
>hemangiosarcoma:-
arising from liver cells.
Benign
>adenomas:-epithelial
origin with gland.
>fibromas-fibrotic cell
origin.
>cholangiofibromas:-
Arise from bile ducts

18. TUMORS

19. CHOLESTASIS
>Refers to decreased or arrested bile flow.
>elevated serum levels-bile salts and bilirubin.
>Impairment of yellowish bilirubin pigment reflects
jaundice.
>Structural changes I
>dilation of the bile canaliculus
>presence of bile plugs in bile ducts and canaliculi.
* Chemical involves- Chlorpromazine, cyclosporin A,
ethanol, ampicillin,estrogens etc.

20. CHOLESTASIS

21. SINUSOIDAL DAMAGE
Its a specialized capillary with numerous fenestrae for
high permeability.
>damages occurs two pathways-
1.Dilation of the sinusoid- whenever efflux of hepatic
blood is impeded. Known as peliosis hepatis.
*Chemials- anabolic steroids ,danazol.
 2.blockade of its lumen- occurs due to enlargement
of fenestrae & red blood cells become caught.
*Chemicals- acetaminophen

22. PELIOSIS HEPATIS

23.  Fatty liver :- Caused by chemicals produce an
accumulation of lipids in the liver, called fatty liver or
steatosis.
> hepatocellular necrosis occurs in specific acinar
zones.
> zone 1 –lipid accumulation from white phosphorus.
>zone 3 -lipid accumulation with tetracycline and
ethanol.
 The lipid accumulates in vacuoles within the cytoplasm.
> macrovesicular steatosis
> microvesicular steatosis
> This vesicular steatosis has been associated with
tetracycline, valproic acid, salicylates, aflatoxin etc.

24. POTENTIAL CHEMICAL EFFECTS GIVE RISE TO
ACCUMULATION OF LIPID
1. Inhibition of Lipoprotein Synthesis.- Eg. carbon
tetrachloride, ethionine.
2. Decreased Conjugation of Triglycerides with
Lipoproteins . Eg.Carbon tetrachloride
3. Interference with Very-Low-Density Lipoprotein
(VLDL) Transfer: Eg. Tetracycline
4. Impaired Oxidation of Lipids by Mitochondria: Eg.
Carbon tetrachloride, ethionine.
5. Increased Synthesis of Fatty Acids: Eg. Ethanol.

25. FATTY LIVER

27. THANK YOU !