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ACH_Nigeria
PHARMACOKINETICS(MONDAY)
CARBON TETRACHLORIDE:
This compound also may damage the liver and, like
acetaminophen, it is not the compound itself but a
derivative of it that is damaging. Free radicals are
formed from carbon tetrachloride by the action of
oxidase enzymes on it. The products of free radical
action are conjugated dienes which arise from lipid
peroxidation. Although the toxicity of carbon
tetrachloride by this mechanism is not proved beyond
any doubt, several lines of evidence support it.
First, carbon tetrachloride exposure can be shown to be
specifically damaging to membranes, which also are
known to be sites for free radical attack. Second,
administration of antioxidants limits damage
caused by carbon tetrachloride. Antioxidants are also
known to reduce free radical formation.Reactive free
radicals have a small radius of action (due to
high reactivity); thus, damage is centered in the
centrilobular region where the activating enzymes are
present in the largest amount. The peroxy radical is
believed to be the main cause of lipid peroxidation.
Renal Toxikinetics
There are two kidneys located in the middle of the
back. Each is supplied with blood by a branch of the
descending aorta called the renal artery. Blood is
filtered by the kidneys and the filtered product,
urine, is passed to the urinary bladder via the
ureters. Each kidney contains about 1,000,000
functional units known as nephrons.
PHARMACOKINETICS(TUESDAY)
RENAL FUNCTION:
The major function of the kidneys is elimination of
waste from the blood. However, many other important
activities are carried out by this organ, including
metabolic processes (although less than the number
carried out by the liver). The kidney also
plays a central role in controlling acid-base balance.
When there is an acid-base imbalance in the blood,
renal compensation can partly offset the effects of
excess acid or base by regulating the rate at which
bicarbonate is excreted into the urine.
The kidney also can contribute to hydrogen ion
homeostasis by producing glutamine from glutamic acid.
This is its major method for dumping excess hydrogen
ion during episodes of metabolic acidosis. Hormonal
activities of the kidney include synthesis of renin
(blood pressure regulation), erythropoietin (red cell
production), and 1,25-dihydroxyvitamin D3, the most
active form of vitamin D, for the absorption and
retention of calcium in the body.
The kidney is especially susceptible to the effects of
toxins for several reasons. In the first place, it
receives a disproportionate amount of blood flow. One
might expect that the blood flow to the kidney would be
small because the kidneys weigh less than 5 lbs. each.
However, they actually receive 25% of the total blood
flow, undoubtedly because of their important function
in relation to clearing the blood of waste. In
addition, the very fact that the kidneys areresponsible
for concentrating substances in preparation for
excretion means that substances, including toxins,
reach much higher concentrations within the kidney than
within the bloodstream. Last, renal toxicity is
intensified because the kidney, like the liver, is
capable of converting inactive pre-toxins into toxic
substances.
PHARMACOKINETICS(WEDNESDAY)
RENAL FUNCTION:
The major function of the kidneys is elimination of
waste from the blood. However, many other important
activities are carried out by this organ, including
metabolic processes (although less than the number
carried out by the liver). The kidney also
plays a central role in controlling acid-base balance.
When there is an acid-base imbalance in the blood,
renal compensation can partly offset the effects of
excess acid or base by regulating the rate at which
bicarbonate is excreted into the urine.
The kidney also can contribute to hydrogen ion
homeostasis by producing glutamine from glutamic acid.
This is its major method for dumping excess hydrogen
ion during episodes of metabolic acidosis. Hormonal
activities of the kidney include synthesis of renin
(blood pressure regulation), erythropoietin (red cell
production), and 1,25-dihydroxyvitamin D3, the most
active form of vitamin D, for the absorption and
retention of calcium in the body.
The kidney is especially susceptible to the effects of
toxins for several reasons. In the first place, it
receives a disproportionate amount of blood flow. One
might expect that the blood flow to the kidney would be
small because the kidneys weigh less than 5 lbs. each.
However, they actually receive 25% of the total blood
flow, undoubtedly because of their important function
in relation to clearing the blood of waste. In
addition, the very fact that the kidneys areresponsible
for concentrating substances in preparation for
excretion means that substances, including toxins,
reach much higher concentrations within the kidney than
within the bloodstream. Last, renal toxicity is
intensified because the kidney, like the liver, is
capable of converting inactive pre-toxins into toxic
substances.
PHARMACOKINETICS(THURSDAY)
NEPHROTOXICANTS:
METALS;
Metals, particularly heavy ones, are capable of causing
kidney damage. The specific site of damage is usually
the proximal tubules and cell death or impairment
results. At a biochemical level metals bind to
sulfhydryl groups on proteins found in membranes
or in enzymes, and thereby interfere with normal
function leading to various degrees of reduced function
or death. At least one metal, mercury, is believed to
have one additional deleterious action, namely,
constriction of blood vessels with a consequent
reduction of blood flow and oxygen supply to renal
tissue.
Chromium has a different effect from mercury. It
inhibits glucose reabsorption by damaging the proximal
convoluted tubule, the site of glucose re-uptake.
Chromium toxicity depends greatly on the oxidation
state of chromium. If the oxidation state is 3+, the
chromium is relatively nontoxic and is absorbed to a
very limited degree. When the oxidation state is 6+,
however, the chromium is reduced by intracellular
enzymes. In the process, free radicals are formed and
disrupt many cellular processes.
Lead is a heavy metal which is taken up by proximal
tubule cells. Within these cells lead interferes with
mitochondrial biochemistry. The cell has some ability
to detoxify lead and appears to do this to some degree
by forming inclusion bodies of lead bonded to acidic
proteins. Such bodies, which appear before lead
toxicity starts, may be seen as microscopic inclusions
within the cell.
Cadmium (atomic weight = 112.4, density = 8.6 g/mL) is
somewhat different from other metals, being a common
cause of kidney damage. It has a very long halflife
PHARMACOKINETICS(FRIDAY)
NEPHROTOXICANTS:
METALS;
Metals, particularly heavy ones, are capable of causing
kidney damage. The specific site of damage is usually
the proximal tubules and cell death or impairment
results. At a biochemical level metals bind to
sulfhydryl groups on proteins found in membranes
or in enzymes, and thereby interfere with normal
function leading to various degrees of reduced function
or death. At least one metal, mercury, is believed to
have one additional deleterious action, namely,
constriction of blood vessels with a consequent
reduction of blood flow and oxygen supply to renal
tissue.
Chromium has a different effect from mercury. It
inhibits glucose reabsorption by damaging the proximal
convoluted tubule, the site of glucose re-uptake.
Chromium toxicity depends greatly on the oxidation
state of chromium. If the oxidation state is 3+, the
chromium is relatively nontoxic and is absorbed to a
very limited degree. When the oxidation state is 6+,
however, the chromium is reduced by intracellular
enzymes. In the process, free radicals are formed and
disrupt many cellular processes.
Lead is a heavy metal which is taken up by proximal
tubule cells. Within these cells lead interferes with
mitochondrial biochemistry. The cell has some ability
to detoxify lead and appears to do this to some degree
by forming inclusion bodies of lead bonded to acidic
proteins. Such bodies, which appear before lead
toxicity starts, may be seen as microscopic inclusions
within the cell.
Cadmium (atomic weight = 112.4, density = 8.6 g/mL) is
somewhat different from other metals, being a common
cause of kidney damage. It has a very long halflife
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