Xenobiotics Elimination in Renal System

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Questions and Answers

What is the primary pathway for the elimination of xenobiotics through the renal system?

Biliary elimination

Direct secretion into intestine

Biotransformation

Filtration and excretion (correct)

Which process significantly contributes to fecal excretion of xenobiotics?

Facilitated diffusion

Biliary elimination (correct)

Glomerular filtration

Active transport

What characterizes the metabolites of xenobiotics when they are excreted into bile?

They are typically more hydrophilic (correct)

They are typically less soluble

They are typically more hydrophobic

They remain unchanged

What role does the liver have in the elimination of xenobiotics from the blood?

It filters xenobiotics from the GI tract Signup and view all the answers

What might the excretion of xenobiotics via feces be a result of?

Both B and C Signup and view all the answers

What is the approximate blood flow rate to the kidneys of an adult human?

1 L/min Signup and view all the answers

Which part of the kidney is primarily responsible for filtration?

Glomerulus Signup and view all the answers

Approximately how many nephrons does an adult human kidney contain?

1 million Signup and view all the answers

What proportion of blood plasma is filtered by the glomerulus?

33% Signup and view all the answers

What mechanism is primarily responsible for the reabsorption of xenobiotics into the blood?

Active transport Signup and view all the answers

What is a primary characteristic of the filtration membrane in the kidneys?

It contains large pores for small molecules Signup and view all the answers

How does pH influence retention in the renal tubule?

It alters ionization of compounds. Signup and view all the answers

What role does passive diffusion play in renal excretion?

It is primarily for lipid-soluble compounds. Signup and view all the answers

What is a characteristic of protein transport systems in the kidneys?

They can become saturated. Signup and view all the answers

How does urine alkalinization affect the excretion of weak acids?

It increases their excretion by ionizing them. Signup and view all the answers

What is an effect of highly bound plasma proteins on renal clearance?

They have no impact on active transport. Signup and view all the answers

What condition can cause impairment of kidney function?

Kidney stones. Signup and view all the answers

Which factor directly influences the glomerular filtration rate?

Cardiac output. Signup and view all the answers

When renal clearance is discussed, which property compares with lipophilic and hydrophilic substances?

Log Kow values. Signup and view all the answers

What is a potential cause of bladder and kidney infections?

Enteric bacteria entering the urethra. Signup and view all the answers

Which of the following is NOT a consequence of kidney disease?

Improved homeostasis. Signup and view all the answers

What is the role of the hepatic portal vein in relation to xenobiotics?

It transports xenobiotics from the gut directly to the liver. Signup and view all the answers

Which of the following is true regarding biliary excretion?

Biliary excretion is influenced by the molecular weight of compounds. Signup and view all the answers

What characterizes Class B substances in terms of their concentration ratios?

Their ratio of bile to plasma usually falls between 10 and 1000. Signup and view all the answers

Which of the following factors influence biliary excretion?

The physicochemical properties of the substances. Signup and view all the answers

What is a major fate of lipophiles that enter systemic blood via the hepatic vein?

They may be secreted intracellularly or excreted into bile. Signup and view all the answers

What is one key function of hepatocytes in relation to lipophiles?

Hepatocytes excrete intracellular lipophiles into bile. Signup and view all the answers

Which of the following statements is correct about phase 3 metabolism in the liver?

It encompasses both facilitated diffusion and active transport mechanisms. Signup and view all the answers

What are xenobiotics with a low molecular weight more likely to be subjected to?

Reabsorption via enterohepatic circulation. Signup and view all the answers

What is the elimination half-life (t1/2) used to measure?

The persistence of a xenobiotic in the body Signup and view all the answers

How does biliary excretion affect lipophilic xenobiotics?

It accelerates their elimination through active transport. Signup and view all the answers

What mechanism limits the biliary excretion of lipophilic substances?

Enterohepatic circulation. Signup and view all the answers

What terminology is used to describe the concentration of a chemical within body tissues?

Body burden Signup and view all the answers

Why are lipophilic xenobiotics often poorly excreted through the kidneys?

Tubular reabsorption occurs in kidney pathways. Signup and view all the answers

What characterizes Persistent Organic Pollutants (POPs)?

They are highly lipophilic and bioaccumulative. Signup and view all the answers

What role do conjugation reactions play in the elimination of lipophilic xenobiotics?

They increase solubility for easier excretion. Signup and view all the answers

What is a major challenge in biomonitoring studies of body burden?

Direct sampling of body tissues is often not possible. Signup and view all the answers

What role do beta-glucuronidases play in enterohepatic circulation?

They hydrolyze conjugated lipophiles in the gut. Signup and view all the answers

How do lipophilic xenobiotics enter the bloodstream after excretion into bile?

By passive diffusion in the small intestine. Signup and view all the answers

What effect does enterohepatic circulation have on the clearance of lipophilic xenobiotics?

It slows their clearance. Signup and view all the answers

What can the liver do to prevent enterohepatic cycling of lipophiles?

Biotransform lipophiles into hydrophilic compounds. Signup and view all the answers

Which statement about Diethylstilbestrol (DES) is correct?

It undergoes enterohepatic circulation. Signup and view all the answers

What is the main consequence of lipophilic xenobiotics being deconjugated in the intestinal tract?

Enhanced retention of the xenobiotics in the body. Signup and view all the answers

What is a primary mechanism through which the liver excretes xenobiotics?

Biliary excretion through efflux pumps. Signup and view all the answers

Which group of individuals was historically exposed to Diethylstilbestrol (DES)?

Pregnant women receiving the drug. Signup and view all the answers

Study Notes

HLTH 340: Toxicokinetics of Elimination

Xenobiotics are eliminated via the urinary system, which consists of the kidneys, ureters, bladder, and urethra.
For xenobiotic excretion, the primary focus is on the role of the kidneys.
The kidney has two main functions: excretion of metabolic waste and regulation of water and ion content in the blood.
Blood flow to the kidneys in adults is roughly 1 L/min. A majority of waste materials are eliminated within this time.
Kidneys play a role in regulating blood volume by controlling the amount of water that is excreted and reabsorbed.
Kidney function in regulating blood pressure, sodium, potassium, and hydrogen regulation.
Kidneys play a part in producing red blood cells via erythropoietin.
The kidneys are made up of many nephrons which filter blood for urine production.
The renal artery carries blood to the kidneys and the renal vein carries blood away from the kidneys.
The nephron is the most important part of the kidney and contains approximately 1 million nephrons per kidney.

Elimination via the Urinary System

There are four primary mechanisms involved in urinary excretion: filtration, passive diffusion, active transport, and facilitated diffusion.
Filtration involves smaller molecules in the blood being filtered to the beginning of the renal tubule. About 99% of the filtrate is reabsorbed back into the blood, and the remaining 1% is excreted as urine.

Renal Ultrafiltration and Selective Tubular Reabsorption

Glomerular filtration: About one-third of blood is filtered through the glomeruli. This creates a filtrate.
Tubular secretion: PCT selectively secretes certain xenobiotics into urine.
Tubular reabsorption: DCT and collecting duct (CD) may reabsorb many xenobiotics from the urine into the blood through passive diffusion.

Passive Diffusion

This is a major route for lipid-soluble compounds.
If the compound remains non-ionized, passive diffusion and reabsorption are high
Ionisation in the tubules is necessary for the compound to be excreted.

Active Transport

Carrier proteins are used to move chemicals from the blood into the tubular lumen.
Protein transport systems are specific for weak acids or bases.
These systems may become saturated, limiting the excretion rate of a given compound.

Facilitated Diffusion

This is a process similar to active transport, but without the need for energy.

Other factors affecting urinary excretion

Plasma protein binding: Highly bound compounds have decreased glomerular filtration, however, active transport is unaffected.
pH: Alkalinization of urine increases excretion of weak acids by maintaining them in the ionized state. The opposite is true for weak bases.

Xenobiotic Efflux Pumps

Active transport of hydrophobic endobiotics and xenobiotics by ABC transporters (P-gp/MDR1 & MRP).

Renal Excretion and Reabsorption

The movement of substances (excretion and reabsorption) is done via membrane transporters.

Biliary Elimination

A critical pathway for eliminating xenobiotics (and metabolites).
First-pass effect: Liver filters out a fraction of lipophiles before the blood enters general circulation.
Metabolites are excreted directly into the bile.
Substances excreted into the bile are divided into three classes (A, B, and C), based on their plasma to bile ratio.

Enterohepatic Circulation

Reabsorption of xenobiotics via the gut and re-entry into the liver.
Enzymes (in the intestines, such as beta-glucuronidase) can hydrolyze compounds (making them more lipophilic) aiding in reabsorption and prolonging the presence in the body.
Many organic compounds are conjugated for excretion into bile, but, in the gut, they're deconjugated, making them more lipophilic.

Lipophilic Xenobiotics

Elimination is often difficult due to reabsorption through passive diffusion and enterohepatic circulation.

Phase 3 Metabolism in the Liver

Bile plays a major part in Phase 3 metabolism.

Hepatotoxicity: Cholestasis

Cholestasis is the reduction/stoppage of bile flow, resulting in accumulation of bile in hepatocytes.
Causes include disorders in the liver, bile duct, or pancreas.
Symptoms associated with cholestasis include yellow skin/eyes, skin itching and dark urine/light-colored stools.
Can lead to liver toxicity.

Failures of Homeostasis

Causes of kidney and bladder infections.
Problems associated with poor kidney/bladder function and toxins.

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Description

This quiz focuses on the elimination pathways of xenobiotics through the renal system. It explores the roles of the kidneys, liver, and various processes involved in the excretion of these compounds. Test your knowledge on the mechanisms of filtration, reabsorption, and the characteristics of metabolites involved in this process.