Primary urine

Water solubility (polarity) is essential for excretion. Even though lipid-soluble compounds may also be excreted to primary urine, they are usually at least partially reabsorbed. The metabolites formed in the liver and extrahe-patic tissues remain free (i.e., not bound to proteins) and are, therefore, readily excreted. 

The smallest functional unit of the kidney is the nephron. In the glomerular capillary loops, ultrafiltration of plasma fluid into Bowman s capsule (BC) yields primary urine. In the proximal tubules (pT), approx. 70% of the ultrafiltrate is retrieved by isoosmotic reabsorption of NaCl and water. In the thick portion of the ascending limb of Henle s loop (HL), NaCl is absorbed unaccompanied by water. This is the prerequisite for the hairpin countercurrent mechanism that allows build-up of a very high NaQ concentration in the renal medulla In the distal tubules (dT), NaCl and water are again jointly reabsorbed. At the end of the nephron, this process involves an aldosterone-controlled exchange of Na+ against 1C or H. In the collecting tubule (C), vasopressin (antidiuretic hormone, ADH) increases the epithelial permeability for water, which is drawn into the hyperosmolar milieu of the renal medulla and thus retained in the body. As a result, a concentrated urine enters the renal pelvis. 

The kidneys are extremely well-perfused organs, with about 1500 L of blood flowing through them every day. Approximately 180 L of primary urine is filtered out of this. Removal of water leads to extreme concentration of the primary urine (to approximately one-hundredth of the initial volume). As a result, only a volume of 0.5-2.0 L of final urine is excreted per day. 

Resorption. All low-molecular weight plasma components enter the primary urine via glomerular filtration. Most of these are... 

An important function of the secreted H"" ions is to promote HCOs resorption (top right). Hydrogen carbonate, the most important buffering base in the blood, passes into the primary urine quantitatively, like all ions. In the primary urine, HCOa reacts with H"" ions to form water and CO2, which returns by free diffusion to the tubule cells and from there into the blood. In this way, the kidneys also influence the C02/HC03 buffering balance in the plasma. 

Electrolytes and other plasma components with low molecular weights enter the primary urine by ultrafiltration (right). Most of these substances are recovered by energy-depen-dent resorption (see p. 322). The extent of the resorption determines the amount that ultimately reaches the final urine and is excreted. The illustration does not take into account the zoning of transport processes in the kidney (physiology textbooks may be referred to for further details). 

Calcium and phosphate ions. Calcium (Ca " ) and phosphate ions are almost completely resorbed from the primary urine by active transport (i.e., in an ATP-dependent fashion). The proportion of Ca "" resorbed is over 99%, while for phosphate the figure is 80-90%. The extent to which these two electrolytes are resorbed is regulated by the three hormones parathyrin, calcitonin, and calci-triol. 

Sodium ions. Controlled resorption of Na"" from the primary urine is one of the most important functions of the kidney. Na" resorption is highly effective, with more than 97% being resorbed. Several mechanisms are involved some of the Na" is taken up passively in the proximal tubule through the junctions between the cells (paracellularly). In addition, there is secondary active transport together... 

Receptors can mediate the action of endogenous signalling compounds and may therefore be viewed as regulatory proteins. Such receptors are the physiological targets for neurotransmitters and hormones. Other types of receptors include enzyme proteins, transport proteins and structural proteins. For example, statins inhibit an enzyme catalysing the synthesis of cholesterol and loop diuretics inhibit an enzyme that facilitates the re-uptake of salt in primary urine. 

There are four main compartments a soluble macromolecule can enter the central compartment (blood and lymphatic system), interstitium, intestinal lumen, and lysosomes [100, 101]. Minor compartments are primary urine, liquor, bile, etc. There is no experimental evidence that clearly indicates the penetration of synthetic macromolecules into the cytoplasm, i.e, into the intracellular compartment (inside the cell but outside the endosomes or lysosomes) [101]. The movements of soluble macromolecules between body compartments have been extensively reviewed [14, 20,100-104] and will not be covered in detail here. We shall concentrate on the discussion of main factors influencing the movement of soluble macromolecules when administered into the bloodstream. Depending on the structure and molecular weight distribution, part of the polymeric molecules are excreted in the urine. Simultaneously, the macromolecules are cleared from the bloodstream by endocytosis. It is important to note that nonspecific capture of soluble macromolecules by the specialized cells of the reticuloendothelial system is generally much less (orders of magnitude) when compared to vesicular carriers of a comparable structure. 

The vasopressins cause reabsorption of water by increasing renal permeability, thus concentrating the primary urine. If the vasopressin level is too low, the reabsorption of water is no longer ensured, so that large quantities of urine of low specific gravity are excreted (water diuresis = diabetes insipidus). With high doses of vasopressin the blood pressure and the intestinal peristalsis are increased. 

Reabsorption of Na+, H20 and many other constituents of primary urine —... 

Such lipid-soluble, non-excretable substances — if subject to glomerular filtration — are almost completely reabsorbed from the primary urine by renal tubules, with the result that they are hardly ever excreted via the kidney. This might involve the danger of accumulations of lipophilic xenobiotics in the body, especially in fatty tissue. Therefore hydrophilization of these substances (with... 

Insect diuretic peptides, two structurally distinct families of diuretic peptides (DP) that stimulate primary urine production by insect Malpighian tubules and regulate water loss from the excretory system. CRH-related diuretic peptides and insect kinins have been found in a number of species, and they may be ubiquitous in insects. CRH-related diuretic peptides belong to the vertebrate CRH/sauvagine/urotensin I/urocortin... 

Glomerular filtrate (i.e., primary urine) is very different from the excreted urine. At each segment of the nephron, passive or active mechanisms will modify the composition of the ultrafiltrate. How the various components of the glomerular filtrate are reabsorbed is detailed below. 

The cortex with glomeruli which create the primary ultrafiltrate the juxtaglomerular apparatus, and the cortical proximal and distal tubules, which are responsible for processing the primary urine thereby maintaining body homeostasis. 

Regulation of the Water Balance. The water balance is regulated chiefly by two mechanisms Thirst, which demands an increased intake of fluids, and the activity of the kidneys, which either conserves water or flushes it out. It is well known that the kidneys produce about 180 liters of primary urine each day. Of this, 178-179... 

Ultrafiltration of plasma the result is primary urine, free of proteins and cells, but with the same concentration of low molecular substances as the plasma. 

Ultrafiltration. This term refers to the filtration of low molecular substances with the retention of high molecular ones, particularly the proteins. Blood proteins are retained in the glomeruli and normally do not enter primary urine at all. Protein in urine is invariably a sign of kidney damage or other diseases. 

The concentration of primary urine to about 1/100 of its original volume demands osmotic work. Calculations show, however, that this osmotic work is almost negligible compared with the total energy production by the kidney. The highly selective process of secretion apparently requires much additional expenditure of energy. 

Most of the low molecular substances that are flushed into the primary urine during ultrafiltration are reabsorbed to a large extent. This is true even for such typical excretion products as urea and uric acid, but especially for free amino acids and glucose, which are reabsorbed completely so long as the blood sugar level stays normal. If the level exceeds 0.16%, some of the sugar is excreted in the urine. Reabsorption is active transport (Chapt. XXI-3) and the enzymic apparatus of active transport can no longer cope with the amounts delivered by the blood. Similar conditions prevail for other substances the capacity for reabsorption (formerly called kidney threshold ) differs widely for various substances. 

Fig. 23.1 A, A -Diacetylspermine (DiAcSpm) production and excretion in the urine. DiAcSpm levels begin to increase in cancer cells in the early stages of cancer development. In the kidney, free polyamines and monoacetylpolyamines in the primary urine are reabsorbed in the rentil proximal tubules. DiAcSpm is not reabsorbed and is eventually excreted in the urine...

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