Lecture 14 Flashcards
What is nephrotoxixty?
It is the rapid deterioration of the kidneys due to toxic effects from drugs
Functions of the kidney:
-Excretion via urine
-Regulation of extra cellular fluid volume
-Regulation of electrolyte composition
-Regulation of acid-base balance
-Synthesis and release of hormones
What is the functional unit of the kidney?
The nephron
How does the nephron work?
In two steps:
1. Glomerulus filters the blood
2. Tubules return necessary substances to the blood and remove waste
Why is the kidney vulnerable to toxins?
-Large blood supply
-Concentration of urine
-Metabolism (reactive intermediates)
-High oxygen demand (susceptible to hypoxia)
What is hypoxia?
When the cell doesn’t get enough oxygen
Substances that cause nephrotoxicity?
-Metals (cadmium, Mercury, lead)
-Herbicides (Paraguat)
-Organic solvents (toluene)
-Halogenated hydrocarbons (bromobenzene)
-Therapeutic agents (paracetamol)
How is actúe renal failure caused?
By the abrupt decline in glomerular filtration rate (GFR)
Acute renal failure can have what effects?
- Tubular effects which causes obstruction backleak
- Vascular effects which causes decreased renal blood flow
What is Paraguat toxicity
A herbicide that is toxic to kidney, liver heart and lungs
-It generates free radicals resulting in cell death and can breakdown photosynthesis in plants
What does oronasal breathers mean?
Organism that insane through the nose and the mouth e,g Humans
What are conducting airways?
-Trachea
-Bronchi
Where does gas exchange occurs
Alveoli
Function of the lungs
- Transport oxygen to other organs
- Eliminate CO2
What is the driving force for ventilation?
It is the pressure difference between the atmosphere and the intra-pulmonic pressure in the alveoli
Inspiration:
Negative active process
-Causes contraction of respiratory muscles
Expiration
Positive negative process
What makes The lungs vulnerable to toxins?
-Large surface area
-Oxidative burden
-Rich blood supply
-Primary route of exposure
Pulmonary disease caused by toxins:
-Pulmonary fibrosis
-Emphysema
-Lung cancer
Pulmonary Fibrosis:
Caused by Paraquat (herbicide)
Leads to decreased gaseous exchange mechanisms
Emphysema:
-Caused by Tobacco smoke
-Leads to lungs not effectively exchanging O2 and CO2
Lung cancer:
Caused by Tobacco smoke
-Leads to formation of a tumor that blocks the airway
How may neurotoxicity occur:
-Specialized metabolic requirement of the brain
-High energy demand of the brain
-Signal transmission across the extra cellular space
-Spatial extension of the nervous system
Types of Neutotoxic injury:
-Neuronopathy
-Axonopathy
-Myelinophathy
-Transmission toxicity
Neuronopathy:
-Caused by Aluminium
-Leads to Dementia
Axonopathy:
-Caused by acrylamide
-Leads to sensory neuropathy
Myelinopathy:
-Caused by hexachlorophen (antiseptic)
-Leads to seizures
Transmission toxicity:
-Caused by nicotine overdose
-Leads to a coma
Protection for potential neurotoxins:
Blood brain barrier (BBB)
Toxic responses of cardiovascular system is caused by:
Direct action: Cardiovascular specific toxin
Indirect action: Toxic changes in other organ systems
Toxic responses of cardiovascular system leads to:
-Structural damage (necrosis)
And
-Functional damage (impaired contractility, abnormal electrical activity)
Examples of diseases caused by cardio toxic effects:
-Arrhythmia
-Aortic lesions
-Cardio-depression action
-Cardiomyopathy
-Depressed contractility
Arrhythmia
-If caused by toluene (pain solvents), ketones or halogenated hydrocarbons (aerosols) it leads to a decrease in parasympathetic CNS activity
-If caused by cocaine it inhibits the mitochondria
Aortic lesions:
-Caused by Mercury
-Results in inhibition of amino acid uptake
Cardio depression action:
-Caused by antibacterial agents
-Leads to disturbed calcium homeostasis
Cardiomyopathy:
-Caused by anti-neoplastic agents (anthracyclines)
-Leads to altered calcium handling and toxic metabolite formation
Depressed contractility:
-Caused by anesthetics (halothane)
-Leads to disturbed calcium homeostasis
