The two kidneys in the body are located in the lumbar region (near the middle of the back, behind the abdominal cavity, just below the rib cage). Each kidney contains about 1 million nephrons. Each nephron consists of a renal corpuscle and a renal tubule.
A renal corpuscle is composed of a filtering unit consisting of a cluster of blood capillaries called glomerulus and a surrounding thin-walled, sacklike structure called a glomerular corpuscle (also known as Bowman’s capsule).
Afferent arterioles arising from larger vessels in the general circulation give rise to this cluster of capillaries, which lead to efferent arterioles, ultimately carrying filtered blood back to the general circulation. the glomerular capsule is an expansion at the end of a renal tubule that receives the fluid filtered through the glomerulus from the circulation.
Normal Physiology of Kidney
Filtration is a key kidney function and is the first step that occurs in the kidneys for the purpose of removing various substances from the blood that will ultimately be eliminated from the body (e.g., excess sodium, waste products, some drugs).
Filtration involves the passage of certain fluid portions of the blood out of the glomerular capillaries through “pores” and into the glomerular capsule; solids such as red blood cells and large proteins are not permitted to cross the capillary barrier.
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The resulting glomerular filtrate is composed mostly of water with some solutes. Solutes that are “freely filterable” include glucose, creatinine, uric acid urea, and electrolytes(e.g. sodium-potassium). The main driving force for this filtration is the pressure of the blood within the glomerular capillaries(i.e. the filtration pressure) that arises from the blood pressure in the general circulation.
Anything that affects the filtration pressure alters the glomerular filtration rate (GFR), which is the rate at which water and molecules cross the glomerular capillary membrane. Constriction of the afferent arterioles (a vessel that delivers blood to the glomerulus of a nephron) would decrease filtration pressure and thus decrease the GFR.
On the other hand, constriction of the efferent arterioles (A vessel that moves blood away from the glomerulus of a nephron) increases the filtration pressure and tends to increase the GFR. Alternatively, cardiovascular disorders such as heart failure, where the heart doesn’t pump effectively to maintain the normal circulation of the blood, may also lead to a reduction in GFR.
The body has a number of systems (e.g. renin-angiotensin system [RAS]) that act on the renal circulation (i.e. afferent and efferent arterioles) to maintain an appropriate filtration pressure and therefore a capital GFR within the normal range. Drugs that have an effect on the RAS may also alter GFR.
Normal renal function is essential for excretion of substances that can be toxic to the body (i.e. will not permit the accumulation of waste products) and to prevent the unhealthy accumulation of certain substances. The normal renal function helps regulate the balance of solutes such as sodium and potassium.
- For example, increased sodium retention may contribute to increased blood pressure or heart failure, while increased levels of potassium may result in heart rhythm abnormalities.
Another function of the kidneys is the elimination of certain drugs from the body. If renal function declines, the blood levels of certain drugs that depend on normal renal function for elimination may increase in the blood.
Drug metabolism and Elimination
A drug may undergo chemical changes while circulating through the body. This chemical convulsion process is called metabolism. Most drug metabolism changes occur in the liver, but they can take place in other tissues as well.
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Various enzymes oxidize (Add Oxygen to) reduce (Remove Oxygen from), or hydrolyze (Add water too) the drug. These changes produce new chemicals or metabolites that may continue to be medically active in the body or may have no activity at all.
A drug may be broken down into one or many different metabolites. Eventually, most drugs or their metabolites circulate through the kidneys, where they are eliminated into the urine. Other routes of elimination of drugs include solid waste through the gastrointestinal (GI) tract, evaporation through perspiration, or through respiration in the lungs (breathing out as part of air exchange).