Distribution and Excretion

Question 1

Chemicals, once absorbed, are distributed
rapidly to body compartments and organs
based on what characteristics?

Answer 1

1..) Physical and chemical properties of chemical
2.) Physical properties of the body compartment
or organ system
3.) Specific binding or receptor mechanics

Question 2

Chemical distributed in body compartments are dependent on what?

Answer 2

Volume of distribution, Vd

Question 3

Partition coefficients of chemicals (Kow) determine what?

Answer 3

Dose of toxic agents in body compartments (Log P)

Question 4

Storage of toxicants in tissues?

Answer 4

1. .) Characteristics of chemical or metabolite
2. ) Characteristics of specific tissues
3. ) Presence of binding proteins
4. ) Dependent on ability to cross cell membranes
5. ) Storage site may not be target site

Question 5

Storage depots - Plasma proteins?

Answer 5

Toxicant can be displaced from plasma protein by another agent resulting in higher levels of free toxicant
- Albumin most common protein binding xenobiotic

Question 6

Factors impacting toxicity? (Binding to plasma proteins)

Answer 6

Blood flow and renal clearance

Question 7

What organs bind more chemicals than all other organs combined?

Answer 7

Liver and kidney

- Mechanism involves active transport (energy req.)

Question 8

How does body weight affect chemicals?

Answer 8

1. .) Chemicals with high Kow accumulate in fats
2. ) Fat people store more chemicals
3. ) Impacts metabolism

Question 9

What chemicals are stored in bone?

Answer 9

Lead, fluoride, strontium

- Process is a surface chemistry process; reversible

Question 10

Characteristics of the blood-brain barrier?*

Answer 10

1. .) Less permeable - characterized by tight junctions between cells
2. ) Lipid soluble - non ionized penetrate
3. ) Water soluble - ionized do NOT penetrate
4. ) NOT fully developed at birth

Question 11

Transport across placenta?

Answer 11

1. .) Placental transfer - Risks to the fetus
2. ) Placenta is NOT an absolute barrier - multilayered
3. ) Nutrients transferred by active transport to fetus
4. ) Xenobiotics by passive diffusion

Question 12

Redistribution depends on what?

Answer 12

1. .) Initial distribution depends on blood flow to organ
   - substance goes where blood flow is highest
2. ) Later, redistribution can occur depending on affinity of the chemical with the organ or storage depot

Question 13

Factors impacting distribution?

Answer 13

1. .) Chemical and physical properties of chemical
2. ) Characteristics of target site
3. ) Characteristics of the transport process

Question 14

Types of excretion or elimination?

Answer 14

1. .) Urinary excretion
2. ) Fecal excretion
3. ) Exhalation
4. ) Other excretion routes - sweat and saliva, milk

Question 15

Characteristics of urinary excretion?

Answer 15

1..) Many substances must undergo biotransformation before being excreted (must be water soluble)
2.) Active transport with many transporter systems
3.) Highly dependent on pH and degree of ionization
4.) Many chemicals reabsorbed
5.) Kidney not fully developed in newborn –
reduced excretion

Question 16

Characteristics of fecal excretion?

Answer 16

1. .) Second major route of excretion – poorly understood
2. ) The non-digestible fraction – straight through
3. ) Biliary excretion

Question 17

Factors impacting biliary excretion?

Answer 17

Active transport involved in some cases*

1. .) Molecular weight > 325 excreted
2. ) Water soluble agents not excreted in bile
3. ) Species specific, fast and slow excreting species

Question 18

Characteristics of exhalation?

Answer 18

Major route of excretion for volatile gases
Elimination depends on:
- Lipid solubility – slowly eliminated
- Water solubility – rapidly eliminated
- Vapor pressure
Mechanism – passive diffusion

Question 19

Factors impacting excretion?

Answer 19

1..) Route of excretion
2.) Physical properties of chemical or
metabolite
3.) Transport proteins or conjugates
4.) Characteristics of excretion pathway