38 Questions
What is the half-life of radioactive caesium (137Cs) in years?
30
Which factor does not affect the absorption of substances in the GI tract?
Blood pressure
What is a characteristic of the skin that affects its absorption of substances?
Must cross several cell layers
What is the similarity between Cs+ and another ion?
K+
In which part of the body does the dissolution of particles occur during absorption?
GI tract
What is the significance of the Fukushima nuclear disaster in relation to the Chernobyl disaster?
The releases of radioactive isotopes from Fukushima and Chernobyl are of the same order of magnitude
What is the primary factor affecting the absorption of gases, vapors, and volatile liquids in the lungs?
Surface area
What is the primary factor determining the selective transport of ions through ion channels?
Size and ionic charge of the ions
What is the primary mechanism of absorption of calcium from the intestine to the blood?
Active transport via the calcium channel
Why is lead absorbed through the same calcium transport channel?
Lead has a similar ionic structure to calcium
What is the primary effect of lead poisoning on children's health?
Neurologic damage and IQ reduction
What is the recommended prevention method for chronic lead poisoning?
Supplementing with vitamin D and calcium
What is the primary function of the iodide transport pump?
Transport of iodide ions
What is the environmental hazard associated with radioactive iodine isotope I-131?
Thyroid cancer
What is the primary factor that determines the rate of passive diffusion across a cell membrane?
Size of the molecule
Which type of transport is characterized by being energy-independent and substrate-specific?
Facilitated transport
What is the primary factor that influences the permeability of endothelium?
Size, shape, and charge of the chemical
Which type of transport can enhance the transport of xenobiotics up to 50,000 folds?
Facilitated transport
What is the maximum size of molecules that can move through cell pores?
< 0.4 nm
Which type of transport is characterized by being independent of or against the concentration gradient?
Active transport
What is the primary function of the P-glycoprotein pump in the context of xenobiotics?
Active transport of xenobiotics
What is the primary factor that determines the rate of blood flow to organs in the distribution phase of toxicokinetics?
Tissue perfusion rate by arterial blood supply
Which of the following tissues is considered highly perfused and more vulnerable to toxic effects?
Liver
What is the effect of a 100-fold increase in free pharmacologically active concentration at the site of action?
A decrease in the toxicity of the xenobiotic
Which of the following barriers can affect the distribution of xenobiotics to target tissues?
Blood-brain barrier (BBB) and blood-testis barrier (BTB)
What is the primary reason why the same dose of a xenobiotic can cause toxicity by one route but not another?
Differences in distribution to target tissues
What percentage of molecules are typically bound to plasma proteins or RBCs in blood?
99.9%
Which of the following factors does not affect the extent of distribution of a xenobiotic?
Blood pressure
What is the primary mechanism by which water-soluble toxicants with a molecular weight of less than 70,000 are excreted through the kidney?
Passive transport
What is the primary function of the liver in the elimination of toxicants?
Metabolism to make toxicants more water-soluble
What is the primary route of excretion for gases and volatile liquids?
Lung
What type of transport is involved in the excretion of conjugates with high molecular weight into bile?
Active transport
What is the primary reason why mother's milk is an important elimination route for toxicants?
Both a and b
What type of toxicants are more likely to be reabsorbed and cause systematic toxicity?
Lipid-soluble toxicants
What is the primary mechanism by which toxicants are excreted from the GIT?
Simple diffusion
What is the role of the kidney in the elimination of toxicants?
To filter and reabsorb toxicants
What is the primary function of biliary secretion in the elimination of toxicants?
To excrete conjugates with high molecular weight
What is the significance of sweat, saliva, and mother's milk as elimination routes for toxicants?
They are minor routes of elimination
Study Notes
Radioactive Contamination
- Radioactive caesium levels are high enough to cause concern in areas of northern Japan 30-50 km from the plant.
- Fukushima releases are of the same order of magnitude as Chernobyl disaster in 1986.
Factors Affecting Absorption
- Determinants of passive transfer: lipid solubility, pH, surface area, concentration gradient, blood flow, and dissolution in the aqueous medium.
- GI absorption: disintegration of dosage form, dissolution of particles, chemical stability, motility, and mixing in the GI tract, and presence and type of food.
- Lungs absorption: large surface area, thin barrier, high blood flow, and rapid absorption for gases, vapors, and volatile liquids.
- Skin absorption: crossing several cell layers to reach blood vessels.
Absorption of Inorganic Ions
- Ion transport channels: selective preference for transporting certain ions, size and ionic charge determine selective transport.
- Cation transport channels: selective channels for transcellular transport of positively charged ions (e.g., calcium, lead).
- Anion transport channels: transport of negative charged ions (e.g., iodide).
Lead as an Environmental Hazard
- Environmental sources: leaded paints, auto exhaust, and pica in young children.
- Lead causes neurologic damage in children: IQ reduction, mild retardation, hyperactivity, and behavioral disorders.
- Prevention of chronic lead poisoning: calcium supplements, diet with milk, high protein intake, and adequate vitamin D.
Cell Membrane and Transport
- Cell membrane: lipid solubility, pH, and surface area affect permeability.
- Endothelium: size, shape, and charge of chemical affect permeability.
- Passive transport: no energy source required, uncharged molecules diffuse along concentration gradient, and lipophilic chemicals diffuse through the lipid bilayer.
- Facilitated transport: energy-independent, may enhance transport up to 50,000 folds, and substrate-specific.
- Active transport: independent of or against concentration gradient, requires energy, and substrate-specific.
Distribution
- Second phase of toxicokinetic process: defines where in the body a xenobiotic will go after absorption.
- Factors affecting distribution: size, molecular weight, lipid solubility, plasma protein or RBC binding, and tissue binding.
- Blood flow to target tissue is affected by internal membrane barriers and sequestration in non-target tissues.
Elimination Routes
- Kidney: major route, including filtration and reabsorption process.
- Liver: changes lipid soluble to more water soluble molecule for excretion in the kidney.
- Biliary secretion: active transport.
- Lung: exhalation of gases and volatile liquids by diffusion.
- Mother's milk: important for transfer to baby and transfer from animals to humans.
Test your understanding of cell membrane structure and function, including passive and active transport mechanisms, permeability, and factors affecting the transfer of molecules across membranes. Learn about the role of lipid solubility, pH, and concentration gradients in determining transport.
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