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فیزیولوژی تکمیلی Advanced Physiology (part 6, Urinary system) By: A. Riasi (PhD in Animal Nutrition & Physiology) Animal Sci. Dep. Isfahan University of Technology http://riasi.iut.ac.ir Respiratory system  Reference: Urinary Systems  Vertebrate kidneys come in a variety of morphologies and functional capacities. Urinary Systems  Mammalian kidneys have four major functions:  Regulating major inorganic solutes  Regulating plasma volume  Regulating of harmful or unneeded organic molecules  Control the osmotic balance Urinary Systems  In mammals, kidneys have the following additional functions  Secretion of erythropoietin  Secretion of renin, a hormone important for salt conservation  Conversion of vitamin D into its active form  Excretion of pheromones for sexual signaling, marking territories, and so forth Urinary Systems  Nephrons are functional unit of each kidney:  Tubular component  Vascular component Urinary Systems Urinary Systems Urinary Systems  The three layers for glomerular filtration:  The glomerular capillary wall consists of a single layer of flattened endothelial cells.  The basement membrane, a non-cellular gelatinous layer composed of collagen and glycoproteins   The collagen provides structural strength  Thee glycoproteins discourage the filtration of small plasma proteins The inner layer of Bowman’s capsule. It consists of podocytes (podo, “foot”), octopus-like cells that encircle the glomerular tuft. Urinary Systems  Bowman’s capsule podocytes Urinary Systems  Three physical forces for glomerular filtration Urinary Systems  Autoregulation of GFR Urinary Systems Urinary Systems  Two intrarenal mechanisms involve in autoregulation  The myogenic mechanism A common property of arteriolar vascular smooth muscle, which contracts inherently in response to the stretch accompanying increased pressure within the vessel.  The tubuloglomerular feedback (TGF) mechanism  Involves the juxtaglomerular apparatus (JGA). Urinary Systems  Within the wall of the afferent arteriole, the smooth muscle cells in the JGA are specialized.  The distal tubule at JGA are specialized and known as macula densa.  The macula densa detect changes in the salt level of the fluid flowing past them through the tubule. Urinary Systems  In response to the resultant rise in salt delivery to the distal tubule, the macula densa cells release ATP and adenosine.  These are paracrines, which act on the adjacent afferent arteriole, causing it to constrict and thus reducing glomerular blood flow and returning GFR to normal. Urinary Systems  In the opposite situation, when less salt is delivered to the distal tubule because of a spontaneous decline in GFR accompanying a fall in arterial pressure, the macula densa releases less paracrines.  The resultant afferent arteriolar vasodilation increases the glomerular flow rate, restoring the GFR to normal. Urinary Systems  To exert even more exquisite control over TGF, the macula densa cells also secrete the vasodilator nitric oxide.  By means of the TGF mechanism, the tubule of a nephron is able to monitor the salt level in the fluid flowing through it and adjust its own GFR accordingly to maintain fluid and salt delivery in the distal tubule. Urinary Systems  The myogenic and TGF mechanisms work in unison to autoregulate the GFR during the transient changes in blood pressure that accompany daily activities unrelated to the need for the kidneys to regulate H2O and salt excretion. Urinary Systems  If autoregulation did not occur, the GFR could increase and H2O and solutes would be lost needlessly whenever arterial pressure rises during intense activity.  If the GFR were too low, the kidneys could not adequately eliminate unneeded materials. Urinary Systems Urinary Systems  The GFR can be influenced by changes in the filtration coefficient (Kf).  Research indicates that Kf is subject to physiological control.  Two factors affect the Kf:  The surface area  The permeability of the glomerular membrane Urinary Systems  The surface area available within the glomerulus is represented by the extent of the capillary surface.  Each tuft of glomerular capillaries is held together by mesangial cells.  Contraction of the mesangial cells reduces the radius of the filtering capillaries, which reduces the surface area available.  Sympathetic stimulation causes the mesangial cells to contract, thus providing a second mechanism (besides afferent arteriolar vasoconstriction) by which sympathetic activity can decrease the GFR. Urinary Systems  Podocytes also possess actin like contractile filaments.  The contraction or relaxation can, respectively, decrease or increase the number of filtration slits open in the inner capsule. membrane of Bowman’s Urinary Systems  Tubular reabsorption Urinary Systems  Reabsorption of most substances occurs in the proximal tubule.  Tubular reabsorption involves two transepithelial transport methods, and act highly selective:  Passive transepithelial transport  Active transepithelial transport Urinary Systems  Mammalian tubules typically reabsorb 99% of the filtered H2O and salt and 100% of the filtered glucose and amino acids.  The tight junctions largely prevent substances except H2O from moving between the cells.  So materials must move transcellularly to leave the tubular lumen and gain entry to the blood. Urinary Systems  Substances that are actively reabsorbed against a gradient and are of particular importance to the body include:  Organic nutrients such as glucose and amino acids  Electrolytes such as Na+and PO43− Urinary Systems  The waste products remaining in the tubular fluid become highly concentrated.  Urea molecules passively reabsorbed in peritubular capillaries as a result of this concentrating effect.  About 40% of the filtered urea is passively reabsorbed and only 60% of the fitered urea is eliminated. Urinary Systems Urinary Systems  Effect of the renin–angiotensin–aldosterone system (RAAS)  Angiotensinogen is a plasma protein synthesized by the liver and always present in the plasma in high concentration.  Once renin secreted into the blood convert angiotensinogen into angiotensin I.  In the lungs, angiotensin I is converted into angiotensin II by angiotensin-converting enzyme (ACE). Urinary Systems  Angiotensin II is the primary stimulus for the secretion of the hormone aldosterone from the adrenal cortex. These do the following effects:  Na+ reabsorption  Water retention  Vasoconstriction  Thirst and salt hunger Urinary Systems Urinary Systems  The second route of entry selected substances into the tubules is tubular secretion.  The most important substances secreted by the tubules are:  Hydrogen ion (H+)  Potassium (K+)  Organic anions and cations Urinary Systems  Hydrogen ion can be added to the filtered fluid by being secreted by the proximal, distal, and collecting segments, using proton-pumping.  The extent of H+ secretion depends on the acidity of the body fluids. Urinary Systems  Potassium secretion is controlled by aldosterone.  Changes in the plasma K+ concentration can be dangerous and causes heart arrhythmia.  Potassium ion is selectively moved in opposite directions in different parts of the tubule.  It is actively reabsorbed in the proximal tubule  It can also actively secreted by principal cells in the distal and collecting tubules Urinary Systems Urinary Systems  During periods of K+ depletion, K+ secretion in the distal portions of the nephron is reduced to a minimum.  The K+ secretion, not the filtration or reabsorption of K+, is varied in a controlled fashion to regulate the rate of K+ excretion and maintain the desired plasma K+ concentration. Urinary Systems  Several factors can alter the rate of K+ secretion, the most important being aldosterone.  An elevation in plasma K+ concentration directly stimulates the adrenal cortex to increase output of aldosterone. Urinary Systems  The manifestations of ECF K+ depletion are:  Skeletal muscle weakness  Diarrhea  Abdominal distention  Abnormalities in cardiac rhythm and impulse conduction