Absorption, Distribution, and Excretion of Toxicants Flashcards
(10 cards)
Biotransformation is vital in removing toxicants from the circulation. All of the following
statements regarding biotransformation are true EXCEPT:
a. Many toxicants must be biotransformed into a more lipid-soluble form before they can
be excreted from the body.
b. The liver is the most active organ in the biotransformation of toxicants.
c. Water solubility is required in order for many toxicants to be excreted by the kidney.
d. The kidney plays a major role in eliminating toxicants from the body.
e. The lungs play a minor role in ridding the body of certain types of toxicant.
Correct Answer: a. Many toxicants must be biotransformed into a more lipid-soluble form before they can be excreted from the body.
Explanation: Biotransformation converts toxicants into more water-soluble forms to aid excretion via the kidneys, not lipid-soluble.
a. FALSE – Lipid-soluble compounds are harder to excrete; biotransformation makes them water-soluble.
b. TRUE – The liver is the main site of biotransformation.
c. TRUE – Water solubility is essential for renal elimination.
d. TRUE – Kidneys eliminate water-soluble metabolites.
e. TRUE – Lungs can excrete volatile substances but play a minor role.
Which of the following statements about active transport across cell membranes is FALSE?
a. Unlike simple or facilitated diffusion, active transport pumps chemicals against an
electrochemical or concentration gradient.
b. Unlike simple diffusion, there is a rate at which active transport becomes saturated and
cannot move chemicals any faster.
c. Active transport requires the expenditure of ATP in order to move chemicals against
electrochemical or concentration gradients.
d. Active transport exhibits a high level of specificity for the compounds that are being
moved.
e. Metabolic inhibitors do not affect the ability to perform active transport.
Correct Answer: e. Metabolic inhibitors do not affect the ability to perform active transport.
Explanation: Active transport requires ATP. Metabolic inhibitors block ATP production, inhibiting active transport.
a. TRUE – Active transport works against gradients.
b. TRUE – It can become saturated.
c. TRUE – Requires ATP.
d. TRUE – It is highly specific.
e. FALSE – Metabolic inhibitors do impair active transport.
Which of the following might increase the toxicity of a toxicants administered orally?
a. increased activity of the MDR transporter (p-glycoprotein).
b. increased biotransformation of the toxicant by gastrointestinal cells.
c. increased excretion of the toxin by the liver into bile.
d. increased dilution of the toxin dose.
e. increased intestinal motility.
d Correct Answer: a. Increased activity of the MDR transporter (P-glycoprotein).
Explanation: This one can be tricky. Decreased MDR activity often increases toxicity by allowing more absorption. However, if increased MDR activity leads to efflux failure or is overwhelmed, it may paradoxically increase toxicity systemically. Context-dependent, but per some texts: answer is a.
a. CORRECT in some contexts – May contribute to altered absorption or redistribution.
b. FALSE – Biotransformation often detoxifies the toxicant.
c. FALSE – Increased excretion lowers toxicity.
d. FALSE – Dilution decreases concentration.
e. FALSE – Increased motility reduces time for absorption.
Which of the following most correctly describes the first-pass effect?
a. The body is most sensitive to a toxicant the first time that it passes through the
circulation.
b. Orally administered toxicants are partially removed by the GI tract before they reach
the systemic circulation.
c. It only results from increased absorption of toxicant by GI cells.
d. It is often referred to as “postsystemic elimination.”
e. A majority of the toxicant is excreted after the first time the blood is filtered by the
kidneys.
Correct Answer: b. Orally administered toxicants are partially removed by the GI tract before reaching systemic circulation.
Explanation: First-pass metabolism refers to removal of toxicants by the liver or GI tract before entering circulation.
a. FALSE – Sensitivity isn’t the focus here.
b. TRUE – Correct definition.
c. FALSE – Not solely from increased absorption.
d. TRUE BUT VAGUE – It’s also known as post-systemic elimination, but this doesn’t define it best.
e. FALSE – Excretion by the kidneys occurs later.
Which of the following is an important mechanism of removing particulate matter from the
alveoli?
a. coughing.
b. sneezing.
c. blowing one’s nose.
d. absorption into the bloodstream, followed by excretion via the kidneys.
e. swallowing.
Correct Answer: d
a. Coughing – FALSE (for alveoli specifically)
Coughing clears the trachea and bronchi, not the alveoli, because alveoli don’t have cilia or strong reflexes like larger airways. I initially chose this, but it’s more relevant to upper airway clearance, not alveolar clearance.
b. Sneezing – FALSE
Sneezing is for nasal passages and upper respiratory tract. It doesn’t affect alveolar clearance.
c. Blowing one’s nose – FALSE
Same issue—clears upper airways (nasal cavity), not the alveoli.
**d. Absorption into the bloodstream followed by excretion via the kidneys – ** TRUE for alveoli
The alveoli are thin-walled and highly vascularized, so small particles or gases that reach them may dissolve or cross into the bloodstream, then be metabolized and excreted by the kidneys. This is a key systemic removal route when mechanical clearance isn’t possible.
e. Swallowing – FALSE
Swallowing clears mucus that’s moved up by the mucociliary escalator in the trachea or bronchi, not alveoli.
For a toxicant to be absorbed through the skin, it must pass through multiple layers in order
to reach the systemic circulation. Which of the following layers is the most important in
slowing the rate of toxicant absorption through the skin?
a. stratum granulosum.
b. stratum spinosum.
c. stratum corneum.
d. stratum basale.
e. dermis.
Correct Answer: c. Stratum corneum.
Explanation: The stratum corneum is the outermost layer and major barrier to skin absorption.
a. FALSE – Granulosum is deeper and less protective.
b. FALSE – Spinosum is deeper and less of a barrier.
c. TRUE – Key layer for limiting dermal absorption.
d. FALSE – Basale is deepest; not protective.
e. FALSE – Dermis is vascularized but not a barrier.
A toxicant is selectively toxic to the lungs. Which of the following modes of toxicant
delivery would most likely cause the LEAST damage to the lungs?
a. intravenous.
b. intramuscular.
c. intraperitoneal.
d. subcutaneous.
e. inhalation.
Correct Answer (according to book): c. intraperitoneal
Let’s unpack that and compare it to the reasoning for b. intramuscular, which I originally said.
Option breakdown:
a. Intravenous – This delivers the toxicant directly into systemic circulation, quickly reaching high perfusion organs, including the lungs. Likely to cause damage.
b. Intramuscular – This introduces the toxicant into muscle tissue, from which it is slowly absorbed into systemic circulation. Delays delivery, but the toxicant will still reach the lungs via the bloodstream eventually.
c. Intraperitoneal – Delivery into the peritoneal cavity leads to first-pass metabolism by the liver via portal circulation before systemic distribution. This can reduce the amount of toxicant reaching the lungs, especially for toxicants that are metabolized in the liver.
d. Subcutaneous – Similar to IM; slower absorption, but toxicant still reaches the lungs eventually.
e. Inhalation – Direct exposure to the lungs. Definitely most damaging if the toxicant is lung-selective.
Key Insight:
The intraperitoneal route is special because it often allows for hepatic metabolism before reaching systemic circulation (like oral delivery), so for lung-toxic substances, it can reduce lung exposure. That makes c. intraperitoneal a more defensible answer than b. intramuscular—especially if the toxicant is metabolized well by the liver.
Which of the following is NOT an important site of toxicant storage in the body?
a. adipose tissue.
b. bone.
c. plasma proteins.
d. muscle.
e. liver.
Let’s go option by option:
a. Adipose tissue – TRUE
Adipose is a major storage site for lipophilic (fat-soluble) toxicants like DDT, PCBs, and dioxins.
b. Bone – TRUE
Bone stores toxicants like lead, strontium, and fluoride due to their chemical similarity to calcium.
c. Plasma proteins – TRUE
Proteins like albumin bind and carry toxicants in the blood, serving as a temporary storage reservoir.
d. Muscle – DEBATABLE (Book’s Answer)
Muscle can store certain toxicants like cadmium and some pesticides, but it’s not a major or consistent site across toxicants. It may be a less important site compared to adipose, bone, or plasma proteins.
e. Liver – FALSE as storage (My Original Answer)
The liver is the primary site of metabolism and biotransformation, not long-term storage. It processes toxicants but does not typically store them long-term unless metabolism is overwhelmed.
So who’s right—book or explanation?
If the question is asking strictly about “storage,” the liver is less of a long-term depot than the others.
Muscle, however, is less significant overall as a storage site, so the book marking d as the answer is also defensible—especially if you’re ranking based on frequency or volume of storage across known toxicants.
Final takeaway:
Correct answer (book): d. muscle is acceptable for test purposes.
But e. liver is also justifiable if interpreted as “not primarily for storage.”
For flashcards: you might want to add a clarifier:
“Muscle is a relatively minor site of toxicant storage compared to adipose, bone, and plasma proteins. The liver is mainly for metabolism, not storage.”d Correct Answer: e. Liver.
Explanation: The liver is a site of metabolism, not storage. Other sites sequester toxicants for long durations.
a. TRUE – Adipose stores lipophilic toxicants.
b. TRUE – Bone can bind metals.
c. TRUE – Plasma proteins bind circulating toxicants.
d. TRUE – Muscle can accumulate some chemicals.
e. FALSE – Liver processes, but doesn’t store long-term.
Which of the following regarding the blood–brain barrier is TRUE:
a. The brains of adults and newborns are equally susceptible to harmful blood-borne
chemicals.
b. The degree of lipid solubility is a primary determinant in whether or not a substance can
cross the blood–brain barrier.
c. Astrocytes play a role in increasing the permeability of the blood–brain barrier.
d. Active transport processes increase the concentration of xenobiotics in the brain.
e. The capillary endothelial cells of the CNS possess large fenestrations in their basement
membranes.
Correct Answer: b. The degree of lipid solubility is a primary determinant in whether or not a substance can cross.
Explanation: The BBB allows lipid-soluble compounds through, restricting water-soluble or large molecules.
a. FALSE – Infants have immature BBB and are more susceptible.
b. TRUE – Lipid solubility is key.
c. FALSE – Astrocytes support, but don’t increase permeability.
d. FALSE – Active transport can reduce brain concentrations.
e. FALSE – CNS capillaries have tight junctions, not fenestrations.
Which of the following will result in DECREASED excretion of toxic compounds by the
kidneys?
a. a toxic compound with a molecular weight of 25,000 Da.
b. increased activity of the multidrug-resistance (MDR) protein.
c. increased activity of the multiresistant drug protein (MRP).
d. increased activity of the organic cation transporter.
e. increased hydrophilicity of the toxic compound.
The kidney filters compounds primarily through glomerular filtration, which has a size cutoff of about 60–70 kDa, but filtration efficiency drops sharply for compounds over 20–30 kDa. A molecule weighing 25,000 Da (25 kDa) is large enough that it cannot be effectively filtered, meaning its renal excretion is decreased.
Now let’s review each option:
a. TRUE – Large molecules like this are poorly filtered by the kidney → Decreased excretion
b. FALSE – MDR proteins are efflux transporters that pump xenobiotics out into urine or bile → Increased excretion
c. FALSE – MRP (also an efflux transporter) contributes to enhanced renal and biliary excretion
d. FALSE – Organic cation transporters (OCTs) enhance uptake into renal tubules, facilitating excretion
e. FALSE – Hydrophilic compounds are more water-soluble and more easily excreted via kidneys
So why might the book say d?
If the book lists d as the correct answer, it may be a typo or interpretation issue—because organic cation transporters increase excretion, not decrease it. Option a is physiologically the most defensible and aligns with standard toxicokinetics.