Urinary System Lecture 3 PDF

S1 L3 PHYSIOLOGY Urinary System Lecture 3 Explained by : Muhammad Zaid Edited by : Hussain Jawad Objective 1) Regulation of tubular reabsorption 2) Renal clearance 3) Renal mechanisms for controlling urine concentration and Dilution 4) Body control of...

S1 L3 PHYSIOLOGY Urinary System Lecture 3 Explained by : Muhammad Zaid Edited by : Hussain Jawad Objective 1) Regulation of tubular reabsorption 2) Renal clearance 3) Renal mechanisms for controlling urine concentration and Dilution 4) Body control of ECF osmolarity 1) Regulation of tubular reabsorption by: 1-Glomerulotubular Balance 2-Peritubular capillary and renal interstitial fluid physical forces 3-Effect of arterial pressure on urine output—the pressure-natriuresis and pressure-diuresis mechanisms 4- Hormonal control of tubular reabsorption 5-Sympathetic activity: Increase tubular reabsorption of sodium ions 1-Glomerulotubular Balance ❑ It is the intrinsic ability of the tubules to increase their reabsorption rate in response to increased filtered load (increase GFR), this balance occurs in proximal tubules and less in loop of henle. ❑ This mechanism is independent of hormones, the glomerulotubular balance prevents overloading of the distal tubular segments when GFR increases and it is a second line of defense to buffer the effects of spontaneous GFR changes on urine output, while the first line of defense is the tubuglomerular feedback. ❑ Autoregulation & glomerulotubular balance prevent large changes in fluid flow in the distal tubules when arterial pressure changes or other disturbances occur. 2-Peritubular capillary and renal interstitial fluid physical forces ❑ Normally more than 99 % of the water and solutes are reabsorbed from tubule lumen to interstitium and then to the peritubular capillaries. ❑ Changes in peritubular capillary reabsorption rate can influence by physical forces (hydrostatic and colloid osmotic pressures) in the renal interstitium surrounding the tubules. ❑ The normal peritubular capillary reabsorption rate is about 124 ml/min, which is calculated as:Tubular Reabsorption (TR) = Kf * Net reabsorptive force=12.4*10 mm Hg =124 ml/min ❑ The Net reabsorptive force about 10 mm Hg favors reabsorption into the peritubular capillaries which represents the sum of the forces include : Factors affecting tubular reabsorption ❖ Factors affecting tubular reabsorption The same previously mentioned Starling forces affect tubular reabsorption in addition to other factors. ❖ The following equation summarizes some of these factors. ❖ TR = Kf * (net reabsorption pressure) ❖ TR = Kf * (Pif – Pc + Πc – Πif ) ❖ TR = Kf * (6 mmHg – 13 mmHg + 32 mmHg – 15 mmHg) ❖ TR = Kf * (+10 mmHg) ❖ Where Kf is another factor contributing to reabsorptionIt is a constant that depends on the surface area of effective reabsorption, distance of reabsorption and tubular capillary permeability. ❖ Starling forces: ❖ Pif is interstitial fluid hydrostatic pressure (favoring). ❖ Pc is peritubular capillaries’ hydrostatic pressure (opposing). ❖ IIc is peritubular capillaries’ osmotic pressure of colloids (favoring). ❖ IIif is interstitial fluid osmotic pressure of colloids (opposing). 3-Effect of arterial pressure on urine output—the pressure- natriuresis and pressure-diuresis mechanisms ❖ Even small increases in arterial pressure lead to (decrease in tubuar reabsorption) increase urinary excretion of Na+ and H2O, phenomena ❖ Note; Natriuresis is similar to diuresis ❖ (the excretion of an unusually large quantity of urine), except that in natriuresis the urine is exceptionally salty) ❖ That are referred to as pressure natriuresis and pressure diuresis, these contribute to several factors: 1- A slight increase in GFR (autoregulation). 2- A slight increase in peritubular capillary hydrostatic pressure. 3- A reduced angiotensin II formation. 4- Hormonal control of tubular reabsorption : A- Aldosterone: ❑ Secreted from the adrenal cortex ❑ And acts on principal cells of the cortical collecting tubule to increase reabsorption of sodium ions and potassium ions secretion are by stimulation sodium-potassium (Na-K ATPase) pump in the basolateral of the cortical collecting tubule membrane. A- Aldosterone ❑Adrenal insufficiency, the absence of aldosterone (Addison’s disease) results in excessive sodium loss and potassium retention or accumulation ❑ while adrenal hyperactivity, excess aldosterone secretion (occursin adrenal tumors), (Conn's syndrome) results in sodium retention and potassium depletion. B- Angiotensin II: ❑ Important in low blood pressure and/or low extra-cellular fluid volume such as, hemorrhage or loss of salt & water. ❑ Helps to return blood pressure & extracellular volume toward normal. Produced by the lungs from angiotensin I this in turn ❑ produced in the liver from angiotensinogen (renin). ❑ Angiotensin increase sodium ions and water reabsorption especially in the proximal tubule through three main effects: B- Angiotensin II: 1) Stimulation of aldosterone. 2) It constricts the efferent arterioles leading to reduced peritubular capillary hydrostatic pressure & increases the concentration of proteins and the colloid osmotic pressure in the peritubular capillaries. 3) It stimulates Na+- K+ ATPase pump as well as Na+-HCO3-co- transport on the basolateral membrane and stimulating Na+- H+exchange in the luminal membrane. C- Antidiuretic hormone ADH (vasopressin): ❑ Produced from posterior pituitary gland ❑ And it acts on water channels (aquaporins) in distal and collecting tubules and ducts to increase water reabsorption and urine concentration. D- Atrial natriuretic peptide (ANP): ❑ Produced by specific cells of cardiac atria in response to any increase in blood volume ❑ and acts especially on collecting ducts to decrease sodium &water reabsorption and so, increase urine excretion to restore normal blood volume. ❑ ANP also inhibits renin secretion and therefore angiotensin II formation, reduces renal tubular reabsorption. ❑ ANP levels are greatly elevated in congestive heart failure and help attenuate sodium and water retention in heart failure. E- Parathyroid hormones: ❑ Produced by parathyroid glands ❑ And act especially on thick ascending limbs of Henle’s loops and distal tubules to increase calcium and magnesium ions reabsorption and decrease phosphate reabsorption. 5-Sympathetic activity: Increase tubular reabsorption of sodium ions. ❑ It decreases sodium and water excretion (increase tubular reabsorption) By: ❑ First- constricting renal arterioles, thus reducing GFR. ❑ Second- increasing Renin release & Angiotensin II formation. 2) Renal clearance Renal clearance: is the volume of plasma that is completely cleared of the substance by the kidneys per unit time. Renal clearance is useful in measuring (1) the excretory function of the kidneys (2) renal blood flows rate (3) The basic functions of the kidneys: glomerular filtration, tubular reabsorption, and tubular secretion.  CS = (US × V) / PS. Thus, the renal clearance of a substance (Cs), is calculated from (Us × V) the urinary excretion rate of that substance divided by its plasma conc (Ps). Us is the urine conc. of that substance, and V is the urine flow rate. If a substance is freely filtered and is not reabsorbed or secreted by the renal tubules, then GFR can be calculated as the clearance of this substance as follows GFR = (US*V) / Ps = Cs  Inulin is a polysaccharide which not produced in the body, is found in the roots of certain plants and must be administered intravenously to a patient. Creatinine is used clinically, it is a by-product of muscle metabolism and is cleared from the body fluids almost entirely by glomerular filtration (more suitable because no need for intravenous infusion as in inulin). ❑ It is not a perfect marker of GFR, because a small amount of it is secreted by the tubules , so the amount of creatinine excreted slightly exceeds the amount filtered.  Inulin Clearance in GFR Estimation ✓ Inulin is freely filtered & not reabsorbed or secreted, thus rate of excretion in urine equal the rate of substance filtered by the kidney. ✓ GFR = Cin, and Cin = Uin × V / Pin. ✓ So, GFR = Uin × V / Pin = 125 ml/min. ✓ But inulin is not produced by the body & has to be injected, so we will replace it with creatinine.  Comparisons of inulin clearance with clearances of different solutes. ❑ The following generalizations can be made by comparing the clearance of a substance with the clearance of inulin , the gold standard for measuring GFR: (1) If the clearance rate of the substance equals that of inulin ,the substance is only filtered and not reabsorbed or secreted  Comparisons of inulin clearance with clearances of different solutes. 2) if the clearance rate of a substance is less than inulin clearance, the substance must have been reabsorbed by the nephron tubules. (3) if the clearance rate of a substance is greater than that of inulin, the substance must be secreted by the nephron tubules. 3) Renal mechanisms for controlling urine concentration and Dilution Sources of Water Output & Input Water input Food & drink = 2.2 L/day Cellular respiration: Glucose + O2 → CO2 + H2O = 0.3 L/day Water output Urine = 1.5 L/day Fecal matter = 100 mL/day Evaporative{skin & respiration} = 900 mL/day  Regulation of ECF osmolarity ❑ Normal ECF osmolarity is about 280-300 mosm\L and it is mostly dependent on sodium ions concentration (142 mEq\L). ❑ Normal daily sodium ions intake must equals its daily output = 10-20mEq. ❑ When Posm decreases; kidneys excrete large amounts of diluted urine (down to 50 mosm\L) ❑ while when Posm increases; kidneys excrete small amounts of highly concentrated urine (up to 1200 mosm\L).  Regulation of ECF osmolarity ❑ The human body must get rid of not less than 600 mosm of metabolic wastes/day. ❑ So, it is very necessary to excrete not less than 0.5 liters of highly concentrated urine daily. ❑ The obligatory urine volume, can be calculated as: 600 (mOsm /day) / 1200 (mOsm/ L) = 0.5 L / day. ❑ The kidney’s ability to concentrate urine requires the presence of a hyperosmotic medulla (the processes by which renal medullary interstitial fluid becomes hyperosmotic); created by countercurrent mechanism and urea recirculation in concert with ADH.  Antidiuretic hormone (ADH) (vasopressin) ❑ Formation of dilute urine when antidiuretic hormone (ADH) levels are very low. ❑ When ingestion excess water or when there is excess water in the body and extracellular fluid osmolarity is reduced ❑ The secretion of ADH by the posterior pituitary decreases, thereby reducing the permeability of the distal tubule and collecting ducts to water, which causes excreting large amounts of dilute urine.  Antidiuretic hormone (ADH) (vasopressin) ❑ Formation of a concentrated urine when antidiuretic hormone (ADH) levels are high. ❑ When there is a deficit of water and osmolarity of the body fluids increases above normal, the posterior pituitary gland secretes more ADH, which increases the permeability of the distal tubules and collecting ducts to water and decreases urine volume without obviously alter the rate of renal excretion of the solutes Countercurrent mechanism ❑ An osmotic gradient is formed in the interstitial space around the loop of Henle that raises from "the top to the bottom” of the loop. ❑ The action of the “tritransporter” of the epithelial cells of the ascending limb, the water permeability of the descending limb, and the shape of the loop give such osmotic gradient. ❑ The process by which this occurs is called counter-current multiplication. ❑ The descending and ascending limbs of Henle's loop and vasa recta run a long distance parallel, counter and in close proximity to each other carrying solutes toward medulla and water toward systemic circulation resulting in hyperosmotic medulla. Countercurrent mechanism ❑ Ascending limbs of Henle’s loop are called countercurrent multipliers because they continuously bring new NaCl to medulla while ascending vasa recta are called countercurrent exchangers because they continuously drawback water ❑ Note: The countercurrent mechanism: depends on the special anatomical arrangement of the loops of Henle (countercurrent multiplier) and the vasa recta(countercurrent exchange), in addition to the collecting ducts. The countercurrent multiplier steps are: The operation start at loop of Henle assume that it is filled with fluid with a concentration of 300mOsm/L. Active transport of Na and CI out of thick ascending limb from the tubular lumen to the interstium& increase interstium osmolarity. This creates a high osmotic gradient between the interstial fluid and the fluid in the thin descending loop of Henle which is permeable to water.  The countercurrent multiplier steps Movement of water by osmosis from the thin descending loop of Henle to the interstitial fluid leading to increase the osmolarity of tubular fluid equal to interstium osmolarity. The steps are repeated over and over, so the continuous in flow of isotonic tubular fluid from proximal tubule without flow hypotonic tubular fluid into the distal tubule occurs. ❑ With sufficient time, this process gradually traps solutes in the medulla more than water and multiplies the concentration gradient along the medulla, eventually raising the interstitial fluid osmolarity to 1200 to 1400 mOsm/L in the medulla pelvic tip.  Countercurrent exchange in the vasa recta ❑ The vasa recta serve as countercurrent exchangers, minimizing washout of solutes from the medullary interstitium out to the circulation. ❑ In which Plasma flowing down the descending limb of the vasa recta becomes more hyperosmotic up to 1200 at its tip because of diffusion of water out of the blood and diffusion of solutes from the renal interstitial fluid into the blood due to medulla hyperosmolarity.  Countercurrent exchange in the vasa recta ❑ In the ascending limb of the vasa recta, solutes diffuse back into the interstitial fluid and water diffuses back into the vasa recta. ❑ Thus the solute will recycle in the medulla without loss while the water by passes it. ❑ Without the U shape of the vasa recta capillaries, large amounts of solutes would be lost from the renal medulla  Recirculation of urea from medullary collecting duct to Loop of Henle ❑ When the blood concentrations of ADH are high, water is reabsorbed rapidly from the cortical collecting tubule and inner medullary collecting ducts, causing a higher concentration of urea in the tubular fluid. ❑ This lead to large amount of urea is passively reabsorbed from the inner medullary collecting ducts into interstitial fluid.  Recirculation of urea from medullary collecting duct to Loop of Henle ❑ This urea diffuses from interstitial fluid into the thin loop of Henle, (while the thick ascending loop of Henle to the medullary collecting ducts, indicate that these segments are not very permeable to urea)and then passes through the distal tubules, and finally passes back into the collecting duct and so. ❑ The recirculation of urea through these terminal parts of the tubular system several times before it is excreted, trap urea in the renal medulla leading to renal medulla hyperosmolarity.  Recirculation of urea from medullary collecting duct to Loop of Henle ❑ This is essential to save body fluid when water shortage (water deficit). ❑ Urea contributes about 40 to 50 % of the renal medullary interstitium osmolarity (500-600 mOsm/L)when the kidney is forming maximally concentrated urine. ❑ The people, who eat a high-protein diet, give up large amounts of urea as a nitrogenous “waste”product, can concentrate their urine much better than people whose protein intake and urea production are low. ❑ Malnutrition is associated with great impairment of urine concentrating ability. Recirculation of urea from medullary collecting duct to Loop of Henle Note: About one half of the filtered urea is excreted. Urea excretion rate is determined by two factors: (1) The concentration of urea in the plasma. (2) the glomerular filtration rate. 4) Body control of ECF osmolarity 1- Osmoreceptors-ADH feedback 2- Thirst center in brain stem 3- Salt appetite center in brain stem  Osmoreceptor cells: ❑ Lie in anterior hypothalamus ❑ Are sensitive to any increase in Na+ concentration ❑ And send signals to supraoptic nuclei, which stimulate the posterior pituitary gland to increase secretion of ADH that increases water reabsorption. ❑ Vasopressin secretion is also stimulated by decreased blood volume, decreased blood pressure, nausea, vomiting, morphine and nicotine. ❑ Vasopressin secretion is inhibited by increased blood volume, increased blood pressure and alcohol intake. ❑ Increased osmolarity also stimulates the thirst center in brain stem to increase the desire for water intake and also to increase secretion of ADH. ❑ Thirst center is also stimulated by decreased ECF volume, decreased blood pressure, angiotensin II and dryness of mouth, pharynx and esophagus while it is inhibited by decreased ECF osmolarity, increased ECF volume, increased blood pressure andgastric distension Decreased osmolarity stimulates salt appetite center in the brain stem to increase the desire for salt intake. ❑ The two primary stimuli that increase salt appetite are: (1) Decreased extracellular fluid sodium concentration (2) Decreased blood volume or blood pressure, associated with circulatory insufficiency. ❑ The neuronal mechanism for salt appetite is analogous to that of the thirst mechanism.  S 1 L1 THANK YOU