77 Questions
What may result from exposure to a toxin causing high blood pressure resulting in cardiac hypertrophy?
Cardiomyopathies
What is the result of Na+ Channel Blockade?
Reduction of conduction velocity and prolonged QRS duration
What may xenobiotic-induced constriction of the coronary vasculature result in?
Ischemia
What is the consequence of inhibition of Na+, K+-ATPase?
Increased intracellular Na+
What is the mechanism of action of K+ Channel Blockade?
Increases duration of the AP
What may result in the production of toxic oxygen radicals, leading to subsequent tissue damage?
Ischemia-Reperfusion Injury
What is the consequence of Ca2+ Channel Blockade?
Causes a negative inotropic effect
What is the result of interference with ion homeostasis?
Disturbances in cardiac function
What is the primary contractile unit in cardiac muscle tissue?
Cardiac muscle cell (myocyte)
Which cells have limited proliferative capacity in the heart?
Myocytes
What sets the pace of the heart's electrical conduction?
Sinoatrial (SA) node
What records electrical currents of the heart?
Electrocardiogram (ECG)
What regulates cardiac activity by stimulating cardiac rate and contractility?
Sympathomimetics
What is the crucial role played by the ATPase sarcoplasmic reticulum pump (SERCA) in cardiac myocytes?
Availability of ATP and Ca2+ for contraction and relaxation
What is the measurement of cardiac output (CO) dependent on?
Heart rate and stroke volume
What may toxicants affect in the cardiovascular system?
Heart, vasculature, and/or the nervous system
What may result from disturbances in cardiac function?
Abnormal heart rhythm, ischemic heart disease, cardiac hypertrophy, and heart failure
What is the result of interference with ion homeostasis in the heart?
Disturbances in heart rhythm
What is the overview of the ventricular action potential (AP) in the heart?
Involves different phases including resting, initiation, plateau, and re-polarization
Which cells are involved in electrical conduction in the heart?
Pacemaker cells such as the sinoatrial (SA) node, atrioventricular (AV) node, bundle of His, and Purkinje fibers
Which part of the eye has a high number of Na+,K+-ATPase sites and can be affected by digoxin?
Retina
Which toxicant disrupts oxidative phosphorylation in rod and cone photoreceptors?
Methanol
What part of the eye does carbon disulfide affect, causing optic atrophy and depressed visual sensitivity?
Optic nerve
Which toxicant may result in structural, biochemical, and functional deficits in the visual cortex in addition to retinal effects?
Lead
What is the primary barrier to percutaneous absorption in the skin?
Stratum corneum
Which type of contact dermatitis accounts for over 90% of reported causes?
Irritant contact dermatitis
Which enzyme in the skin contributes to its barrier function by metabolizing agents as diffusion occurs?
Cytochrome p450
What is the major component of the skin that constitutes 90% of its composition?
Dermis
What is the consequence of prolonged immersion on the effectiveness of the stratum corneum as a barrier?
Reduces effectiveness
Which anatomical site displays faster diffusion through the epidermis than others?
Some anatomical sites
Which toxicant causes tunnel vision and damages a portion of the visual cortex involving the peripheral visual field?
Methyl mercury
Which part of the eye consists of retinal cells that carry information from the retina to the CNS?
Optic nerve
Which part of the eye is highly vulnerable to toxicant-induced damage?
Retina
What may cause a decrease in the optical transparency of the lens?
UV radiation
Which substance may react with proteins in the lens, producing adducts that act as light scattering complexes?
Corticosteroids
What is the transparent body in the eye that focuses visual images on the retina?
Lens
Which medication, administered for schizophrenia, may combine with melanin to form a photosensitive product that reacts with sunlight?
Phenothiazines
What may result from exposure to solvent vapors?
Corneal repair
What is the primary target site for organic solvents that are lipophilic?
Cornea
Which environmental factor may lead to the yellow coloration of the lens?
UV radiation
What may cause irreversible loss of retinal function and blurred vision?
Chloroquine and hydroxychloroquine
Which substance may penetrate both the aqueous and lipid layers of the cornea and may be irritating?
Surfactants
What may lead to the production of toxic oxygen radicals, subsequently causing tissue damage?
UV radiation
What may cause damage to the corneal epithelium and repair likely over a few days?
Organic solvents
What are the three layers of the tear film?
Superficial lipid, underlying aqueous, and thin mucoid layer
Which layer of the cornea acts as the external barrier to the internal ocular structures?
Epithelium
What are the layers of the cornea?
Epithelium, stroma, and endothelium
Which part of the eye includes uveal and retinal vessels with distinct properties?
Ocular vascular system
What can influence toxicity by binding certain substances in the eye?
Intraocular melanin
What type of enzymes are involved in ocular drug metabolism?
Phase I and II xenobiotic transforming enzymes
What governs the penetration of toxic compounds into the visual areas of the CNS?
Blood-brain barrier
Which methods are used for the evaluation of ocular irritancy and toxicity?
Draize Test and EpiOcular
What does the cornea provide for the eye?
Clean, refractive surface, tensile strength, and protection from external factors
What can cause varying degrees of damage to the cornea, iris, ciliary body, and lens?
Acids and bases
What is the primary Ca$^{2+}$ regulatory organelle in cardiac myocytes?
Sarcoplasmic reticulum (SR)
Which toxin may compromise ATP production by affecting oxidative phosphorylation of ADP in the mitochondria?
Cyanide
Which cardiotoxin inhibits Na$^+$, K$^+$-ATPase, leading to an increase in available intracellular Ca$^{2+}$ for contraction?
Digoxin
Which substance acts as a local anesthetic, decreases depolarization rate, slows conduction speed, and promotes arrhythmias?
Cocaine
What may halogenated alkanes cause due to their highly lipophilic nature and ability to cross the blood-brain barrier?
CNS depression
What is the primary role of vascular endothelial cells in the regulation of vascular tone and angiogenesis?
Act as a barrier to toxin movement
What is the primary mechanism of action of tricyclic antidepressants on cardiac myocytes and Purkinje fibers?
Depressing inward Na$^+$ and Ca$^{2+}$ currents
What is the primary effect of antipsychotic agents on cardiovascular function?
Negative inotropic actions
What is the primary effect of general anesthetics on cardiac output and contractility?
Decrease cardiac output and contractility
What is the consequence of halothane (anesthetic) blocking Ca$^{2+}$ channels in the cardiovascular system?
Disrupts Ca$^{2+}$ homeostasis
What may result from exposure to a toxin causing high blood pressure and ventricular hypertrophy?
Cardiac hypertrophy
What is atherosclerosis characterized by?
Focal intimal thickenings following smooth muscle cell migration and uncontrolled proliferation
What may result from exposure to excessive vasoconstrictors?
Hypertension, ventricular hypertrophy, atherosclerosis
What can toxicant exposure result in?
Thrombosis, forming semisolid masses in veins and arteries
What are common mechanisms of vascular toxicity?
Alterations in membrane structure and function, redox stress
What do vasculotoxic agents like nicotine and cocaine cause?
Increase heart rate, blood pressure, and vasoconstriction
How does 1,3-Butadiene increase the incidence of cardiac hemangiosarcomas?
Through bioactivation by cytochrome p450
What do all toxicants absorbed into the circulatory system contact before reaching other body sites?
Vascular cells
What may chemically induced disturbances in cardiac function affect?
Heart rate, contractility, conductivity, excitability
What may exposure to toxic chemicals and systemic drugs result in?
Structural and functional alterations in the eye and visual system
What is the first site of action for exposure to the eye and visual system?
Tear film
What is the primary change in vessel wall in atherosclerosis?
Focal intimal thickenings
What is the result of exposure to vasculotoxic agents like nicotine and cocaine?
Increase heart rate, blood pressure, and vasoconstriction
Study Notes
Cardiac Physiology and Function
- The cardiovascular system consists of the myocardium and a network of vascular vessels (arteries, capillaries, veins) that supply cells and tissues with nutrients and remove waste products.
- The primary contractile unit in cardiac muscle tissue is the cardiac muscle cell (myocyte), which is joined by tight gap junctions facilitating action potential propagation.
- The heart comprises various cellular phenotypes, including myocytes, cardiac fibroblasts, vascular cells, Purkinje cells, and connective tissue cells, with limited proliferative capacity of myocytes and promotion of cardiac fibroblast proliferation.
- The ventricular action potential (AP) overview involves different phases, including resting, initiation, plateau, and re-polarization, with specific ion channels opening and closing during each phase.
- Electrical conduction in the heart involves pacemaker cells such as the sinoatrial (SA) node, atrioventricular (AV) node, bundle of His, and Purkinje fibers, with the SA node commonly setting the pace of the heart.
- The electrical impulse migration from the SA node through the atrial muscle, AV node, and bundle of His allows atria to fully contract before ventricles depolarize.
- An electrocardiogram (ECG) records electrical currents of the heart, with different intervals corresponding to conduction through the AV node, ventricular depolarization and repolarization.
- Cardiac activity is regulated by the autonomic nervous system (ANS), with sympathomimetics stimulating cardiac rate and contractility, and parasympathomimetics decreasing the rate of depolarization.
- Excitation-contraction coupling in cardiac myocytes involves the availability of ATP and Ca2+ for contraction and relaxation, with the ATPase sarcoplasmic reticulum pump (SERCA) playing a crucial role.
- Cardiac function is characterized by the recording of electrical currents through an ECG and the measurement of cardiac output (CO) which is dependent on heart rate and stroke volume, typically around 5L/min.
- Toxicants can affect cardiac function through their effects on the heart, vasculature, and/or the nervous system, potentially leading to disturbances in heart rhythm, such as arrhythmias.
- Disturbances in cardiac function may include abnormal heart rhythm, ischemic heart disease, cardiac hypertrophy, and heart failure, with potential implications for myocardial infarction, scar tissue formation, and reduced cardiac output.
Disturbances of Vascular Structure and Function
- Atherosclerosis is a change in the vessel wall involving focal intimal thickenings following smooth muscle cell migration and uncontrolled proliferation, leading to plaque formation and vascular narrowing.
- Hypertension may result from exposure to excessive vasoconstrictors, causing ventricular hypertrophy, atherosclerosis, capillary destruction, and increased vascular permeability.
- Toxicant exposure can result in thrombosis, forming semisolid masses in veins and arteries, which may detach as emboli in smaller vessels.
- Exposure to chemicals through major routes affects vascular cells before other body sites, increasing the risk of toxic insult.
- Common mechanisms of vascular toxicity include alterations in membrane structure and function, redox stress, vessel-specific bioactivation of protoxicants, and accumulation of active toxins in vascular cells.
- Vasculotoxic agents like nicotine, cocaine, and heavy metals can increase heart rate, blood pressure, and cause vasoconstriction.
- 1,3-Butadiene, used in rubber and automobile part production, increases the incidence of cardiac hemangiosarcomas through bioactivation by cytochrome p450.
- All toxicants absorbed into the circulatory system contact vascular cells before reaching other body sites.
- Chemically induced disturbances in cardiac function may affect heart rate, contractility, conductivity, and excitability.
- Exposure to toxic chemicals, vapors, or therapeutic drugs can result in structural and functional alterations in the eye and visual system.
- Toxic chemicals and systemic drugs may affect all parts of the eye, including the cornea, conjunctiva, and eyelids.
- Tear film, with both hydrophobic and hydrophilic properties, is the first site of action for exposure to the eye and visual system.
Test your knowledge of cardiac physiology and function with this quiz. Explore topics such as cardiac muscle cells, ventricular action potential, electrical conduction in the heart, electrocardiogram interpretation, autonomic nervous system regulation, and cardiac function assessment. Brush up on toxicant effects and disturbances in cardiac function.
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