The best measure of filtration, in turn, is clearance, i.e., the removal of waste chemicals from blood per unit time.. Of various chemicals that have been tested as can-didates for deter
Trang 1HALOGENATED HYDROCARBONS
These molecules are likely to damage kidney tissue in the same manner in which they affect the liver They are thought to be activated by cytochrome P450 oxidases producing free radicals which can then attack cell organelles such as cell membranes Halogenated hydrocarbons like chloroform may covalently bind renal tubular cell proteins and thereby disrupt the normal activity of those proteins
ANALGESICS
Aspirin and phenacetin damage the medulla, the inner structure of the kidney where many of the loops and collecting ducts are located They also affect the blood vessels, which may be the reason the medulla is secondarily affected In other words, aspirin inhibits prostaglandin synthesis, thus reducing vasodilation with an eventual effect
on kidney function
ASSESSMENT OF KIDNEY INJURY
BY BIOCHEMICAL TESTING
The kidney’s ability to filter blood depends primarily on the health of the nephron and, within the nephron, on the integrity of the glomerulus Glomerular filtration, therefore, is the best index of filtering ability The best measure of filtration, in turn,
is clearance, i.e., the removal of waste chemicals from blood per unit time Good renal function equals the ability to clear waste chemicals effectively from the blood Clearance is expressed in units of milliliters per minute and equals the volume of blood that is cleared per minute A normal result in humans is approximately
120 mL/min Individuals with serious impairment may have clearances of only
20 mL/min or less These figures are based on the clearance of creatinine, a waste product of muscle metabolism Of various chemicals that have been tested as can-didates for determining the glomerular filtration rate, creatinine is regarded as the best chemical to measure It is not perfect because some creatinine is transferred to the urine by tubular secretion and, therefore, it is not strictly accurate to regard all urinary creatinine as being due to glomerular filtration Nevertheless, creatinine clearance is very close to an exact estimate of the true glomerular filtration rate The formula for creatinine clearance is
where:
Urinary creatinine is in mg/dL.*
Serum creatinine is in mg/dL.*
Urine volume is in mL
* Any concentration unit is acceptable as long as it is the same for both urinary and serum creatinine.
Creatinine clearance =
urinary creatinine concentration( ×urine volume) (serum creatinine×collection time)
Trang 2HALOGENATED HYDROCARBONS
These molecules are likely to damage kidney tissue in the same manner in which they affect the liver They are thought to be activated by cytochrome P450 oxidases producing free radicals which can then attack cell organelles such as cell membranes Halogenated hydrocarbons like chloroform may covalently bind renal tubular cell proteins and thereby disrupt the normal activity of those proteins
ANALGESICS
Aspirin and phenacetin damage the medulla, the inner structure of the kidney where many of the loops and collecting ducts are located They also affect the blood vessels, which may be the reason the medulla is secondarily affected In other words, aspirin inhibits prostaglandin synthesis, thus reducing vasodilation with an eventual effect
on kidney function
ASSESSMENT OF KIDNEY INJURY
BY BIOCHEMICAL TESTING
The kidney’s ability to filter blood depends primarily on the health of the nephron and, within the nephron, on the integrity of the glomerulus Glomerular filtration, therefore, is the best index of filtering ability The best measure of filtration, in turn,
is clearance, i.e., the removal of waste chemicals from blood per unit time Good renal function equals the ability to clear waste chemicals effectively from the blood Clearance is expressed in units of milliliters per minute and equals the volume of blood that is cleared per minute A normal result in humans is approximately
120 mL/min Individuals with serious impairment may have clearances of only
20 mL/min or less These figures are based on the clearance of creatinine, a waste product of muscle metabolism Of various chemicals that have been tested as can-didates for determining the glomerular filtration rate, creatinine is regarded as the best chemical to measure It is not perfect because some creatinine is transferred to the urine by tubular secretion and, therefore, it is not strictly accurate to regard all urinary creatinine as being due to glomerular filtration Nevertheless, creatinine clearance is very close to an exact estimate of the true glomerular filtration rate The formula for creatinine clearance is
where:
Urinary creatinine is in mg/dL.*
Serum creatinine is in mg/dL.*
Urine volume is in mL
* Any concentration unit is acceptable as long as it is the same for both urinary and serum creatinine.
Creatinine clearance =
urinary creatinine concentration( ×urine volume) (serum creatinine×collection time)
Trang 3Cardiac Toxicity
CONTENTS
Conduction System
Overall Cardiac Activity
Cardiac Function and Toxicity: General Principles
Biochemical Mechanisms
Ionic Changes
Energy Changes
Membrane Changes
Free Radical Formation
Classification of Cardiotoxins
Specific Cardiotoxins
Catecholamines
Cancer Chemotherapy
Oxidative Stress Calcium Changes Energy Fluxes Alcohols
Emetine
Metals
Carbon Monoxide
Questions
The cardiovascular system delivers oxygen and other nutrients to the 300 billion cells that make up the human body It also removes waste materials to lungs, kidneys, and other destinations for disposal from the body Other functions such as a role in neuroendocrine control are also part of its activities In an approximate sense, it has two components: a hollow, muscular pump, the heart, and a system of large and small elastic vessels
Some knowledge of cardiac anatomy and physiology is needed to understand the nature of toxic activity by especially cardiotoxic chemicals The heart is found between the lungs in the middle of the chest somewhat skewed (2/3) toward the left
of the breastbone The bottom left corner of the heart is tilted forward and comes close to the surface of the body A normal heart weighs approximately 200 to 400 grams and equals two clenched fists in volume Cardiac anatomy includes four chambers whose walls are composed of muscle, the myocardium The chambers are separated from each other by structures called septa Blood flows between the chambers through openings that are controlled by valves
9
Trang 4Neurological Toxicity
CONTENTS
Anatomy and Physiology of the Nervous System
Cells in the Nervous System
Neurons
Glial Cells
The Nervous System and Susceptibility to Toxins
Protection for the Nervous System
Manifestations of Neurotoxicity
Specific Interference with Normal Neurological Activity
Toxins and Electrical Conduction
Toxins That Attack the Nerve Cell Body
Toxins That Attack Myelin
Toxins That Attack Axons
Toxins That Attack Synaptic Function
Acetylcholine
Botulinum Toxin Nicotine
Muscarine Curare Atropine Scopolamine Biogenic Amines
GABA
Glycine
Tetanus Toxin
Questions
The nervous system is very vulnerable to many toxins because of its central and delicate role in the overall control of bodily activities Within the nervous system a number of actions contribute to coordinated control First, sensory organs evaluate the environment and relay the collected information to other parts of the nervous system The motor system responds to external and internal stimuli Integration of information is a third part of the nervous system’s activity and involves thinking, learning, and memory
10