Chapter 6 (exam 2)

Question 1

liver

Answer 1

• largest organ in body
• chemical factory, enzyme activity
• functions (6): carb storage/metabolism, hormone/waste/xenobiotic metabolism, synthesis of proteins, urea formation, metabolize fats, bile formation
• increase contact with chemicals means suseptible to toxic impacts (reactive metabolites, pharmaceuticals)

Question 2

Liver circulation

Answer 2

• oxygenated blood from hepatic artery (30% cardiac output)
• nutrient rich blood from hepatic portal vein, from interstines. 80% of blood into liver
• “first pass effect” - treat uptake in blood before reaches other areas of the body

Question 3

bile production

Answer 3

produced in liver - gallbladder - GIT - excreted

-nonpolar and phase 2 products

Question 4

Liver Counter Current

Answer 4

• counter flow between bile duct and portal vein.
• flows opposite directions
• blood from portal vein to central vein
• maximize waste removal
• maintain gradient
• diffusion beyonf static equilibrium

Question 5

Liver zones

Answer 5

1: cells immediately adjacent to PV and HA
- most oxygenated blood
2: between 1 and 3
3: cells immediately adjacent to terminal hepatic vein (THV)
- least oxygenated, highly metabolic, good at extracting oxygen, most often impacted

Question 6

Hepatic injury/necrosis

Answer 6

• localized cell damage or death of hepatocytes
• acetominophen overdose - local necrosis in zone 3, highest P450, essential bio molecules are responsible for homeostasis and they are targeted by metabolites (DNA, protein)
• Cell death releases proteases, lipases, Ca²⁺ - cause other cells to die
• NAPQI could bind to active sites or change confirmation, electrophile so could bind to nucleophile
• create adduct - covalently bonded group

Question 7

Lipid Peroxidation

Answer 7

• liver injury
• initiated by radicals (unpaired electrons are unstable and reactive)
• Disrupts membrane integrity - ion balance, water balance, gradients
• propogation - one radical can affect many target molecules
• termination or queching - 2 radicals to form nonradical product

–antioxidents stabalize and quench radicals, typically aromatic and have resonance to stabalize over many atoms, pigmented and colored

Question 8

Lipid peroxidation mechanism

Answer 8

CCl₄ = CCl₃(radical) + Cl(radical) via P450 in liver

• Chloride radical transfered to hydrocarbon (remove H to form HCl and the hydrocarbon radical
• lipid radical
• hydroperoxyl radical
• add RH and form R(radical) aka propagation

Question 9

Other Liver Injuries

Answer 9

• adducts bind to macromolecules (protein, lipids, DNA)
• loss calcium homeostasis
• fatty liver
• cholestasis - decrease bile flow
• vascular
• cirrhosis
• accumulation of fibrous tissue which disrupts flow

Question 10

Blood Test for Lier Injury

Answer 10

serum albumin - synthesized in liver

serum bilirubin - liver forms bilirubin glucuronide for excretion in bile. dysfuntion is exhibite by jaundice

drug clearance rates - used mostly in research, administer a drug and evaluate clearance from blood plasma

Question 11

Chaparral

Answer 11

• from creosote bush
• botanical extract w/antioxidant activity
• claimed to help things from skin rash to cancer
• liver injury via inhibit P450s, cyclooxygenases and lipoxygenases
• NDGA is antioxidant in chaparral that was a food additive that was removed from the market many years before chaparral was removed
• look for ALT (in the liver cell) in the blood which is due to necrosis and enzyme leaking into the blood
• Elevated alkaline phosphatase (ALP) are from decreased bile flow and indicate injury to duct or vessels