Urine Formation. Urinary Physiology Urinary Section pages Urine Formation. Glomerular Filtration 4/24/2016

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1 Urine Formation Urinary Physiology Urinary Section pages 9-17 Filtrate Blood plasma minus most proteins Urine <1% of total filtrate Contains metabolic wastes and unneeded substances Urine Formation 1. Glomerular filtration 2. Tubular reabsorption Returns components to blood Glucose, amino acids, water and salt 3. Tubular secretion Reverse of reabsorption Selective addition to urine 4. Water conservation Cortical radiate artery Three major renal processes: Glomerular filtration Tubular reabsorption Tubular secretion Afferent Urine Glomerular capillaries Efferent Glomerular capsule Rest of renal tubule containing filtrate Peritubular capillary To cortical radiate vein Figure Occurs at renal corpuscle Passive process driven by hydrostatic pressure Glomerulus is a very efficient filter Permeable membrane Water and small solutes pushed through filter Large surface area Higher blood pressure Efferent Afferent Glomerular capillary covered by podocytecontaining visceral layer of glomerular capsule (a) Glomerular capillaries and the visceral layer of the glomerular capsule Glomerular capsular space Parietal layer of glomerular capsule Proximal convoluted tubule Podocyte cell body Fenestrations (pores) Cytoplasmic extensions of podocytes Filtration slits Glomerular capillary endothelium (podocyte covering and basement membrane removed) Foot processes of podocyte Figure 25.9a 1

2 Filtration membrane 3 components Fenestrated capillary endothelium Basement membrane Podocytes Allows passage of water and small solutes Fenestrations prevent filtration of blood cells Negatively charged basement membrane repels large anions Fenestration (pore) Capillary Plasma Filtration membrane Capillary endothelium Basement membrane Foot processes of podocyte of glomerular capsule Filtrate in capsular space Filtration slit Slit diaphragm Foot processes of podocyte (c) Three parts of the filtration membrane Filtration slits Podocyte cell body Foot processes Net Filtration Pressure (NFP) Glomerular hydrostatic pressure (HP g ) Capsular hydrostatic pressure (HP c ) Blood osmotic pressure (OP g ) (b) Filtration slits between the podocyte foot processes Net Filtration Pressure (NFP) The pressure responsible for filtrate formation Glomerular capsule Afferent NFP = HP g (OP g + HP c ) 10 mm Hg Net filtration pressure Glomerular (blood) hydrostatic pressure (HP g = 55 mm Hg) Blood colloid osmotic pressure (Op g = 30 mm Hg) Capsular hydrostatic pressure (HP c = 15 mm Hg) Figure

3 Net Filtration Pressure NFP = HP G (OP G + HP C ) = 55 mm Hg (30 mmhg + 15 mmhg) = 10 mmhg Rate (GFR) 125 ml/min 1800 liters of blood through kidneys/day = 1200 ml/min = about 180 liters filtrate/day Factors affecting GFR Kidney disease blood osmo>c pressure, capsular osmo>c pressure Hemorrhage glomerular blood hydrostatic pressure Hypotension Glomerularblood hydrostatic pressure = capsule hydrostatic and blood osmotic pressure = filtration stops! Termed renal suppression GFR is tightly controlled by two types of mechanisms Intrinsic control (renal autoregulation) Act locally within the kidney Extrinsic controls Nervous and endocrine mechanisms that maintain blood pressure and affect kidneys Intrinsic Control Goal = Maintain a nearly constant GFR when MAP is in the range of mmHg Renal autoregulation Mechanisms that cause vasoconstriction of afferent s in response to increased BP Reduces glomerular flow to keep GFR the same Extrinsic Controls Sympathetic nervous system At rest Renal blood vessels are dilated Renal autoregulation mechanisms prevail GFR maintained Extreme stress Norepinephrine and epinephrine released Both cause constriction of afferent s Inhibits filtration Shunts blood to other vital organs 3

4 125 ml/min of filtrate produced Most of this fluid is reabsorbed A selective transepithelial process Includes active and passive process Most occurs in PCT PCT Site of most reabsorption 65% of Na + and water All nutrients Ions Small proteins Transcellular route Luminal membranes of tubule cells Cytosol of tubule cells Basolateral membranes of tubule cells Endothelium of peritubular capillaries Movement via the transcellular route involves: 1 Transport across the luminal membrane. 2 Diffusion through the cytosol. Filtrate in tubule lumen Luminal membrane Solutes Tight junction Transport across the basolateral membrane. (Often involves the lateral intercellular spaces because membrane transporters transport ions into these spaces.) 4 Movement through the interstitial fluid and into the capillary. Lateral intercellular space Tubule cell Paracellular Transcellular Transcellular 2 3 Paracellular 3 Interstitial fluid Capillary endothelial cell 4 4 Basolateral membranes Peritubular capillary The paracellular route involves: Movement through leaky tight junctions, particularly in the PCT. Active transport Passive transport Figure Paracellular route Between cells Limited to water movement and reabsorption of Ca 2+, Mg 2+, K +, and some Na + in the PCT where tight junctions are leaky Sodium Most abundant cation in filtrate Primary active transport out of the tubule cell by Na + -K + ATPase in the basolateral membrane Na + passes in through the luminal membrane by secondary active transport or facilitated diffusion mechanisms 4

5 1 At the basolateral membrane, Filtrate Nucleus Interstitial in tubule Tubule cell fluid lumen Na + 2 3Na + 3Na + 1 Glucose 2K Amino + 2K + 3 acids Some K + ions 4 Vitamins Lipid-soluble 5 substances Cl, Ca 2+, K + 6 Cl and other Tight junction Paracellular ions, urea route Primary active transport Transport protein Secondary active transport Ion channel or aquaporin Passive transport (diffusion) Peritubular capillary Na + is pumped into the interstitial space by the Na + -K + ATPase. Active Na + transport creates concentration gradients that drive: 2 Downhill Na + entry at the luminal membrane. 3 Reabsorption of organic nutrients and certain ions by cotransport at the luminal membrane. 4 Reabsorption of water by osmosis. Water reabsorption increases the concentration of the solutes that are left behind. These solutes can then be reabsorbed as they move down their concentration gradients: 5 Lipid-soluble substances diffuse by the transcellular route. 6 Cl (and other anions), K +, and urea diffuse by the paracellular route. Sodium Low hydrostatic pressure and high osmotic pressure in the peritubular capillaries Promotes bulk flow of water and solutes (including Na + ) Figure Tubular Maximum Transport maximum (T m ) reflects the number of carriers in the renal tubules available When the carriers are saturated, excess of that substance is excreted Example: too much glucose in the blood entering glomerulus will cause glucosuria Reabsorption of nutrients, water and ions Blood becomes hypertonic to filtrate Water is reabsorbed by osmosis Cations and fat-soluble substances follow by diffusion Tubular Secretion Reabsorption in reverse K +, H +, NH 4+, creatinine and organic acids move from peritubular capillaries or tubule cells into filtrate Involves active transport since no concentration gradients in this case 5

6 Na + (65%) Glucose Amino acids H 2 O (65%) and many ions (e.g. Cl and K + ) Milliosmols Cortex (a) (d) Tubular Secretion 300 Some drugs H +, HCO 3 NH + 4 Blood ph regulation (a) Proximal convoluted tubule: 65% of filtrate volume reabsorbed Na +, glucose, amino acids, and other nutrients actively transported; H 2 O and many ions follow passively H + and NH 4+ secretion and HCO 3 reabsorption to maintain blood ph (see Chapter 26) Some drugs are secreted Outer Inner (e) (b) (c) Active transport (primary or secondary) Passive transport Figure 25.18a Principle effects Rids body of Foreign substances (penicillin and other drugs) Nitrogenous wastes Excess K + Controls blood ph: Altering amounts of H + or HCO 3 in urine Variations in Urine Formation Composition varies Fluid volume Solute concentration Variations in Urine Formation Water intake must equal water loss Kidney regulates water loss by producing: Hypotonic urine (dilute) Hypertonic urine (concentrated) Countercurrent Mechanism Osmolality of interstitial fluid (mosm) Role of countercurrent mechanisms Establish and maintain an osmotic gradient Creates hypertonic interstitial fluid within kidney Hypertonic interstitial fluid allows the kidneys to vary urine concentration Active transport Passive transport Water impermeable Countercurrent multiplier The long loops of Henle of the juxtary nephrons create the ry osmotic gradient. Cortex Outer Loop of Henle Inner Figure 25.16a 6

7 Formation of Concentrated Urine Depends on the ry osmotic gradient and the ability to alter permeability of the collecting tubules Collecting duct Descending limb of loop of Henle DCT Cortex Active transport Passive transport osmolarity of extracellular fluid (also plasma volume) ADH release Outer Urea aquaporins in collecting duct Urea H 2 O reabsorptionin collecting duct Inner Small volume of concentrated urine (b) Maximal ADH Small volume of concentrated urine Figure 25.17b Formation of Dilute Urine Active transport Passive transport Collecting duct Filtrate is diluted in the ascending Loop of Henle In the absence of ADH, dilute filtrate continues into the renal pelvis as dilute urine Descending limb of loop of Henle Cortex DCT osmolarity of extracellular fluid ADH release Outer aquaporins in collecting duct Urea Inner H 2 O reabsorptionin collecting duct Large volume of dilute urine (a) Absence of ADH Large volume of dilute urine Figure 25.17a Acid-Base Balance ph affects all functional proteins and biochemical reactions in the body Regulation prevents changes in body s internal environment Alkalosis or alkalemia: arterial blood ph >7.45 Acidosis or acidemia: arterial ph < 7.35 Acid-Base Balance Concentration of hydrogen ions is regulated by 1. Chemical buffer systems in blood Rapid, first line of defense 2. Brainstem respiratory centers Acts within 1 3 minutes 3. Renal mechanisms Most potent Requires hours to days to affect ph changes 7

8 Acid-Base Balance Blood CO 2 + H 2 O H 2 CO 3 HCO 3- + H + Lungs Regulate carbonic acid levels by CO 2 manipulation Kidneys Selectively secrete and reabsorb to maintain ph Acid-Base Balance Most important renal mechanisms: Conserving (reabsorbing) HCO 3 Excreting HCO 3 Secretion of H + H + secretion occurs in the PCT and in collecting tubules Acid-Base Balance Examples Respiratory Acidosis Lungs are unable to eliminate CO 2 adequately Kidneys reabsorb HCO 3, secrete H + (and NH4 + ) Respiratory Alkalosis CO 2 levels are low Kidneys secrete HCO 3, retain H + (and NH4 + ) Filtrate in tubule lumen HCO 3 + Na + HCO 3 4 1CO 2combines with water within the tubule cell, forming H 2CO 3. 2 H2CO 3is quickly split, forming H + and bicarbonate ion (HCO 3 ). H2CO 3 5 CO 2 Tight junction 3aH + is secreted into the filtrate. * Nucleus PCT cell H 2CO 3 CO 2 + 2K+ 3Na+ CA Cl Na + 3bFor each H + secreted, a HCO 3 enters the peritubular capillary blood either via symport with Na + or via antiport with CI. 4 Secreted H+ combines with HCO 3 in the filtrate, forming carbonic acid (H 2CO 3). HCO 3 disappears from the filtrate at the same rate that HCO 3 (formed within the tubule cell) enters the peritubular capillary blood. 2K + ATPase 3Na + HCO 3 H + 3a H+ HCO 3 3b 2 HCO 3 ATPase 6 1 Na+ Peritubular capillary Cl CO 2 5 The H2CO 3 formed in the filtrate dissociates to release CO 2 and. 6 CO2diffuses into the tubule cell, where it triggers further H + secretion. Primary active transport Secondary active transport Simple diffusion Transport protein Carbonic anhydrase Figure Variations in Blood Pressure Variations in Blood Pressure Activity of kidney related to variations in blood pressure Blood pressure and blood volume are related Blood volume is controlled by Solute concentration Water regulation Renal mechanisms influencing blood pressure ADH Water Renin-angiotensin mechanism Sodium Potassium 8

9 Antidiuretic Hormone (ADH) Plasma osmolarity Increases (what could cause this?) Osmoreceptors stimulated Thirst & ADH secretion Water reabsorption(decreased urine output) Increased blood volume Increased blood pressure Produced in adrenal cortex in response to Low blood volume Low blood pressure Low plasma Na + High plasma K + Stimulates K + secretion and Na + reabsorption Changes in plasma sodium levels affect Plasma volume Blood pressure Regulation of sodium balance Na + reabsorption 65% is reabsorbed in the proximal tubules 25% is reclaimed in the Loops of Henle causesactive reabsorptionof remaining Na + in DCT and collecting ducts Water follows Na + How would this affect blood volume and blood pressure? Renin-angiotensinmechanism is the main trigger for aldosterone release Granular cells of JGA secrete reninin response to Sympathetic nervous system stimulation Filtrate osmolality(decreased sodium) Stretch (due to blood pressure) Efferent Afferent Glomerular capsule Glomerulus Efferent Juxtaglomerular apparatus Macula densa cells of the ascending limb of loop of Henle Extraglomerular mesangial cells Granular cells Afferent Parietal layer of glomerular capsule Capsular space Juxtaglomerular apparatus Foot processes of podocytes Renal corpuscle Podocyte cell body (visceral layer) Red blood cell Proximal tubule cell Lumens of glomerular capillaries Endothelial cell of glomerular capillary Mesangial cells between capillaries Renin catalyzes the production of angiotensin II Prompts aldosteronerelease from the adrenal cortex Targets cells of DCT and collecting ducts Initiates sodium reabsorption Causes systemic vasoconstriction Effect on BP? Figure

10 K + (or Na + ) concentration in blood plasma* Renin-angiotensin mechanism Blood Pressure Control Negative feedback inhibits Stimulates Adrenal cortex Releases Targets Kidney tubules 3 main mechanisms Renin-angiotensin system Neural regulation (sympathetic control) ADH release Effects Na + reabsorption K + secretion Restores Homeostatic plasma levels of Na + and K + Figure 26.8 Stretch in afferent Filtrate NaCl concentration in s ascending limb of loop of Henle Granular cells of kidneys Release Renin Angiotensinogen (from liver) Systemic s Causes Vasoconstriction Results in Peripheral resistance Converting enzyme (in lungs) Catalyzes conversion Angiotensin I Angiotensin II Adrenal cortex Secretes Targets Distal kidney tubules Causes Systemic blood pressure/volume Inhibits baroreceptors in blood vessels Sympathetic nervous system Systemic s Causes Vasoconstriction Results in Peripheral resistance Posterior pituitary Releases ADH (antidiuretic hormone) Collecting ducts of kidneys Causes reabsorption Factors Affecting Urine Volume Increased temperature Increases vasodilation and perspiration Decreases blood flow to kidneys Decreased temperature Increases blood flow to kidneys Na + (and ) reabsorption Blood volume Results in Blood pressure stimulates Renin-angiotensin system Neural regulation (sympathetic nervous system effects) ADH release and effects Figure Diuretics Chemicals that increase urine output Osmotic diuretics Substances not reabsorbed Glucose in a diabetic patient ADH inhibitors Alcohol and water Substances that inhibit Na + reabsorption Caffeine, thiazides(class of medications), loop diuretics (inhibit Na + -K + -Cl - symportproteins) Potassium levels are affected by some diuretics Can be extremely dangerous Factors Affecting Urine Output blood pressure blood solute concentration plasma proteins Psychological factors 10

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