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Questions and Answers
What is the primary pathway for the elimination of xenobiotics through the renal system?
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?
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?
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?
What role does the liver have in the elimination of xenobiotics from the blood?
What might the excretion of xenobiotics via feces be a result of?
What might the excretion of xenobiotics via feces be a result of?
What is the approximate blood flow rate to the kidneys of an adult human?
What is the approximate blood flow rate to the kidneys of an adult human?
Which part of the kidney is primarily responsible for filtration?
Which part of the kidney is primarily responsible for filtration?
Approximately how many nephrons does an adult human kidney contain?
Approximately how many nephrons does an adult human kidney contain?
What proportion of blood plasma is filtered by the glomerulus?
What proportion of blood plasma is filtered by the glomerulus?
What mechanism is primarily responsible for the reabsorption of xenobiotics into the blood?
What mechanism is primarily responsible for the reabsorption of xenobiotics into the blood?
What is a primary characteristic of the filtration membrane in the kidneys?
What is a primary characteristic of the filtration membrane in the kidneys?
How does pH influence retention in the renal tubule?
How does pH influence retention in the renal tubule?
What role does passive diffusion play in renal excretion?
What role does passive diffusion play in renal excretion?
What is a characteristic of protein transport systems in the kidneys?
What is a characteristic of protein transport systems in the kidneys?
How does urine alkalinization affect the excretion of weak acids?
How does urine alkalinization affect the excretion of weak acids?
What is an effect of highly bound plasma proteins on renal clearance?
What is an effect of highly bound plasma proteins on renal clearance?
What condition can cause impairment of kidney function?
What condition can cause impairment of kidney function?
Which factor directly influences the glomerular filtration rate?
Which factor directly influences the glomerular filtration rate?
When renal clearance is discussed, which property compares with lipophilic and hydrophilic substances?
When renal clearance is discussed, which property compares with lipophilic and hydrophilic substances?
What is a potential cause of bladder and kidney infections?
What is a potential cause of bladder and kidney infections?
Which of the following is NOT a consequence of kidney disease?
Which of the following is NOT a consequence of kidney disease?
What is the role of the hepatic portal vein in relation to xenobiotics?
What is the role of the hepatic portal vein in relation to xenobiotics?
Which of the following is true regarding biliary excretion?
Which of the following is true regarding biliary excretion?
What characterizes Class B substances in terms of their concentration ratios?
What characterizes Class B substances in terms of their concentration ratios?
Which of the following factors influence biliary excretion?
Which of the following factors influence biliary excretion?
What is a major fate of lipophiles that enter systemic blood via the hepatic vein?
What is a major fate of lipophiles that enter systemic blood via the hepatic vein?
What is one key function of hepatocytes in relation to lipophiles?
What is one key function of hepatocytes in relation to lipophiles?
Which of the following statements is correct about phase 3 metabolism in the liver?
Which of the following statements is correct about phase 3 metabolism in the liver?
What are xenobiotics with a low molecular weight more likely to be subjected to?
What are xenobiotics with a low molecular weight more likely to be subjected to?
What is the elimination half-life (t1/2) used to measure?
What is the elimination half-life (t1/2) used to measure?
How does biliary excretion affect lipophilic xenobiotics?
How does biliary excretion affect lipophilic xenobiotics?
What mechanism limits the biliary excretion of lipophilic substances?
What mechanism limits the biliary excretion of lipophilic substances?
What terminology is used to describe the concentration of a chemical within body tissues?
What terminology is used to describe the concentration of a chemical within body tissues?
Why are lipophilic xenobiotics often poorly excreted through the kidneys?
Why are lipophilic xenobiotics often poorly excreted through the kidneys?
What characterizes Persistent Organic Pollutants (POPs)?
What characterizes Persistent Organic Pollutants (POPs)?
What role do conjugation reactions play in the elimination of lipophilic xenobiotics?
What role do conjugation reactions play in the elimination of lipophilic xenobiotics?
What is a major challenge in biomonitoring studies of body burden?
What is a major challenge in biomonitoring studies of body burden?
What role do beta-glucuronidases play in enterohepatic circulation?
What role do beta-glucuronidases play in enterohepatic circulation?
How do lipophilic xenobiotics enter the bloodstream after excretion into bile?
How do lipophilic xenobiotics enter the bloodstream after excretion into bile?
What effect does enterohepatic circulation have on the clearance of lipophilic xenobiotics?
What effect does enterohepatic circulation have on the clearance of lipophilic xenobiotics?
What can the liver do to prevent enterohepatic cycling of lipophiles?
What can the liver do to prevent enterohepatic cycling of lipophiles?
Which statement about Diethylstilbestrol (DES) is correct?
Which statement about Diethylstilbestrol (DES) is correct?
What is the main consequence of lipophilic xenobiotics being deconjugated in the intestinal tract?
What is the main consequence of lipophilic xenobiotics being deconjugated in the intestinal tract?
What is a primary mechanism through which the liver excretes xenobiotics?
What is a primary mechanism through which the liver excretes xenobiotics?
Which group of individuals was historically exposed to Diethylstilbestrol (DES)?
Which group of individuals was historically exposed to Diethylstilbestrol (DES)?
Flashcards
What is a nephron?
What is a nephron?
The nephron is the functional unit of the kidney, responsible for filtering blood and forming urine.
Explain glomerular filtration.
Explain glomerular filtration.
Glomerular filtration involves filtering blood plasma through the glomerulus, producing dilute urine.
What is tubular reabsorption?
What is tubular reabsorption?
Tubular reabsorption is when certain substances in the filtered urine are reabsorbed back into the blood.
What is tubular secretion?
What is tubular secretion?
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How does filtration work in the urinary system?
How does filtration work in the urinary system?
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What is passive diffusion in the urinary system?
What is passive diffusion in the urinary system?
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Explain active transport in the urinary system.
Explain active transport in the urinary system.
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What is glomerular filtration rate (GFR)?
What is glomerular filtration rate (GFR)?
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Xenobiotic Elimination
Xenobiotic Elimination
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Renal Elimination
Renal Elimination
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Biotransformation
Biotransformation
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First Pass Effect
First Pass Effect
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Biliary Elimination
Biliary Elimination
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What are specific protein transport systems in the kidneys?
What are specific protein transport systems in the kidneys?
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What is facilitated diffusion?
What is facilitated diffusion?
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What is plasma protein binding?
What is plasma protein binding?
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How does pH affect urinary excretion of weak acids and bases?
How does pH affect urinary excretion of weak acids and bases?
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What is renal ultrafiltration?
What is renal ultrafiltration?
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What is selective tubular reabsorption?
What is selective tubular reabsorption?
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What is log Kow?
What is log Kow?
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What is kidney disease?
What is kidney disease?
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First-pass effect by the liver
First-pass effect by the liver
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Xenobiotics
Xenobiotics
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Hepatic portal vein
Hepatic portal vein
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Hepatic artery
Hepatic artery
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Hepatocytes
Hepatocytes
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Bile
Bile
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Biliary excretion
Biliary excretion
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Enterohepatic circulation
Enterohepatic circulation
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What are lipophilic xenobiotics?
What are lipophilic xenobiotics?
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What is the elimination half-life?
What is the elimination half-life?
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Define body burden.
Define body burden.
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How does the liver help eliminate lipophilic substances?
How does the liver help eliminate lipophilic substances?
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What is conjugation in xenobiotic metabolism?
What is conjugation in xenobiotic metabolism?
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Describe Persistent Organic Pollutants (POPs).
Describe Persistent Organic Pollutants (POPs).
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What are the PBT criteria?
What are the PBT criteria?
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Why is it difficult to excrete POPs through bile?
Why is it difficult to excrete POPs through bile?
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What is the enterohepatic cycle?
What is the enterohepatic cycle?
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How does the liver process lipophilic xenobiotics?
How does the liver process lipophilic xenobiotics?
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How does the liver eliminate lipophilic xenobiotics?
How does the liver eliminate lipophilic xenobiotics?
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What is the role of bile in the enterohepatic cycle?
What is the role of bile in the enterohepatic cycle?
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What happens to lipophilic xenobiotics in the small intestine?
What happens to lipophilic xenobiotics in the small intestine?
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How do reabsorbed lipophilic xenobiotics get back to the liver?
How do reabsorbed lipophilic xenobiotics get back to the liver?
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What is the consequence of the enterohepatic cycle?
What is the consequence of the enterohepatic cycle?
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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.
