Blood in the kidneys

The kidneys receive blood through the renal artery (Scheme 3.5). Blood in the kidneys is ultimately filtered through nephrons, the operating unit of the kidney. Each kidney... 

We have mentioned already that the maintenance of proper concentrations of sodium, potassium, calcium, and other ions is of considerable importance to the cell. This maintenance is assisted by the efforts the body as a whole makes to ensure that the ionic composition of the circulating bloodstream should be of constant composition. It achieves this by disposing of unwanted material, mainly by filtering and processing the blood in the kidneys and... 

One important amide is caramide (NH2CONH2), or urea, as it is commonly known. Urea is an end product in the metabolic breakdown of proteins in mammals. It is found in the blood, bile, milk, and perspiration of mammals. When proteins are broken down, amino groups (NH2) are removed from the amino acids. The amino groups are then converted to ammonia (NH3) that are toxic to the body. The toxic ammonia is converted to nontoxic urea in the liver. The urea is filtered out of the blood in the kidneys and passed from the body in urine. 

The plasma half-life of most administered proteins is relatively short, because they are susceptible to a wide variety of metabolic reactions. Rapid hydrolytic degradation of peptide bonds by both nonspecific enzymes and highly structurally selective aminopeptidases, carboxypeptidases, deamidases, and proteinases occurs at the site of administration, while crossing the vascular endothelia, at the site of action, in the liver, in the blood, in the kidney, and in fact, in most tissues and fluids of the body. Overall, the metabolic products of most proteins are not considered to be a safety issue. They generally are broken down into amino acids and reincorporated into new, endogenously biosynthesized proteins. 

Factors controlling calcium homeostasis are calcitonin, parathyroid hormone(PTH), and a vitamin D metabolite. Calcitonin, a polypeptide of 32 amino acid residues, mol wt - SGOO, is synthesized by the thyroid gland. Release is stimulated by small increases in blood Ca " concentration. The sites of action of calcitonin are the bones and kidneys. Calcitonin increases bone calcification, thereby inhibiting resorption. In the kidney, it inhibits Ca " reabsorption and increases Ca " excretion in urine. Calcitonin operates via a cyclic adenosine monophosphate (cAMP) mechanism. 

Parathyroid hormone, a polypeptide of 83 amino acid residues, mol wt 9500, is produced by the parathyroid glands. Release of PTH is activated by a decrease of blood Ca " to below normal levels. PTH increases blood Ca " concentration by increasing resorption of bone, renal reabsorption of calcium, and absorption of calcium from the intestine. A cAMP mechanism is also involved in the action of PTH. Parathyroid hormone induces formation of 1-hydroxylase in the kidney, requited in formation of the active metabolite of vitamin D (see Vitamins, vitamin d). 

Studies show that the main sites of uranium deposition ate the renal cortex and the Hvet (8). Uranium is also stored in bones deposition in soft tissues is almost negligible. Utanium(VI) is deposited mostly in the kidneys and eliminated with the urine whereas, tetravalent uranium is preferentially deposited in the Hvet and eliminated in the feces. The elimination of uranium absorbed into the blood occurs via the kidneys in urine, and most, - 84%, of it is cleared within 4 to 24 hours (8). 

Although the antibacterial spectmm is similar for many of the sulfas, chemical modifications of the parent molecule have produced compounds with a variety of absorption, metaboHsm, tissue distribution, and excretion characteristics. Administration is typically oral or by injection. When absorbed, they tend to distribute widely in the body, be metabolized by the Hver, and excreted in the urine. Toxic reactions or untoward side effects have been characterized as blood dyscrasias crystal deposition in the kidneys, especially with insufficient urinary output and allergic sensitization. Selection of organisms resistant to the sulfonamides has been observed, but has not been correlated with cross-resistance to other antibiotic families (see Antibacterial AGENTS, synthetic-sulfonamides). 

In the kidney, ANG II reduces renal blood flow and constricts preferentially the efferent arteriole of the glomerulus with the result of increased glomerular filtration pressure. ANG II further enhances renal sodium and water reabsorption at the proximal tubulus. ACE inhibitors thus increase renal blood flow and decrease sodium and water retention. Furthermore, ACE inhibitors are nephroprotective, delaying the progression of glomerulosclerosis. This also appears to be a result of reduced ANG II levels and is at least partially independent from pressure reduction. On the other hand, ACE inhibitors decrease glomerular filtration pressure due to the lack of ANG II-mediated constriction of the efferent arterioles. Thus, one important undesired effect of ACE inhibitors is impaired glomerular filtration rate and impaired kidney function. 

In the kidney, bradykinin increases renal blood flow, whereas glomerular filtration rate remains unaffected. 

Erythropoietin (Eprex ) is physiologically produced in the kidney and regulates proliferation of committed progenitors of red blood cells. It is used to substitute erythropoietin in severe anemias due to end stage renal disease or treatment of cancer with cytostatic agents. Side effects include hypertension and increased risk of thrombosis. 

Hyperaldosteronism is a syndrome caused by excessive secretion of aldosterone. It is characterized by renal loss of potassium. Sodium reabsorption in the kidney is increased and accompanied by an increase in extracellular fluid. Clinically, an increased blood pressure (hypertension) is observed. Primary hyperaldosteronism is caused by aldosterone-producing, benign adrenal tumors (Conn s syndrome). Secondary hyperaldosteronism is caused by activation of the renin-angiotensin-aldosterone system. Various dtugs, in particular diuretics, cause or exaggerate secondary peadosteronism. 

Natriuretic peptides are a family of peptide hormones. All of them contain a 17-amino acid long ring that is closed by a disulfide bond between two cysteine residues. ANP (atrial natriuretic peptide) is mainly expressed in the atria of the heart, whereas BNP (B-type natriuretic peptide) is synthesized in the ventricular myocardium. CNP occurs mainly in the endothelium and is thought to have a paracrine function. ANF and BNF lower blood pressure by a direct effect on smooth muscle and on the salt retention in the kidney. Natriuretic peptides bind and activate particulate guanylyl cyclases. 

Anemia may occur in patients with chronic renal failure as tlie result of the inability of the kidney to produce erythropoietin. Erythropoietin is a glycoprotein hormone synthesized mainly in the kidneys and used to stimulate and regulate the production of erythrocytes or red blood cells (RBCs). Failure to produce the needed erythrocytes results in anemia Two examples of drug used to treat anemia associated with chronic renal failure are epoetin alfa (Epogen) and darbepoetin alfa (Aranesp). 

Figure 5,4 Pharmacokinetics. The absorption distribution and fate of drugs in the body. Routes of administration are shown on the left, excretion in the urine and faeces on the right. Drugs taken orally are absorbed from the stomach and intestine and must first pass through the portal circulation and liver where they may be metabolised. In the plasma much drug is bound to protein and only that which is free can pass through the capillaries and into tissue and organs. To cross the blood brain barrier, however, drugs have to be in an unionised lipid-soluble (lipophilic) form. This is also essential for the absorption of drugs from the intestine and their reabsorption in the kidney tubule. See text for further details...

Angiotensin II is a neurohormone produced primarily in the kidney. It is a potent vasoconstrictor and stimulates the production of aldosterone. Together, angiotensin II and aldosterone increase blood pressure and sodium and water retention (increasing ventricular wall tension), cause endothelial dysfunction, promote blood clot formation, and cause myocardial fibrosis. 

---