logging in or signing up urinary system.3 mohanad Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 2368 Category: Education License: All Rights Reserved Like it (0) Dislike it (0) Added: April 07, 2009 This Presentation is Public Favorites: 0 Presentation Description No description available. Comments Posting comment... By: yilian (7 month(s) ago) Its effective Saving..... Post Reply Close Saving..... Edit Comment Close By: ekegg (12 month(s) ago) good Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript Urinary system : Urinary system SMS 1113 Dr. Mohanad R. Alwan Nephron Function : Nephron Function Filtration Selective Reabsorption Tubular Secretion Urine formation : Urine formation Nephrons remove wastes from the blood and regulate water and electrolyte concentrations urine is the final product of the processes of: glomerular filtration tubular reabsorption tubular secretion Slide 4: 14-6 Slide 5: 14-7 Filtration : Filtration Analysis of Glomerular Capillary Dynamics Blood Pressure =55.0 mm Hg O (vs 35 normally) Plasma Coll O.P. =30.0 mm Hg I BC Hydrostatic P. =15.0 mm Hg I 10.0 mm Hg O = Filtration Pressure Regulation of Filtration Pressure : Regulation of Filtration Pressure 14-10 Regulation of Filtration Pressure : Regulation of Filtration Pressure 14-11 Urine formation : Urine formation Urine formation include 3 basic steps Glomerular filtration: 1st step of urine production Water & most solutes in blood plasma move across the wall of glomerular capillaries into the glomerular capsule & then into renal tubule Tubular absorption: when filtered fluid flows along the renal tubule & through collecting duct, tubule cells reabsorb 99% of filtered water & useful solutes Re-absorped water & solutes return to blood through peritubular capillaries & vasa recta Tubular secretion: when filtered fluid flows through renal tubule& collecting ducts, tubule & duct cells secrete other materials (wastes, drugs, excess ions) into the filtered fluid Urine formation : Urine formation Glomerular Filtration substances move from blood to glomerular capsule Tubular Reabsorption substances move from renal tubules into blood of peritubular capillaries glucose, water, urea, proteins, creatine amino, lactic, citric, and uric acids phosphate, sulfate, calcium, potassium, and sodium ions Tubular Secretion substances move from blood of peritubular capillaries into renal tubules drugs and ions Glomerular Filtration : Glomerular Filtration Rate (GFR): 120 mL/min (normal) Substances “Filtered”: water, electrolytes (Na, K, etc.), sugars (glucose), nitrogenous waste (urea, creatinine) Substances “Excluded”: Substances of size > 70 kDa Plasma protein bound substances Glomerular Filtration : Glomerular Filtration Glomerular Filtration : Glomerular Filtration The first step in urine formation is filtration of substances out of the glomerular capillaries into the glomerular capsule Glomerular filtrate passes through the fenestrae of the capillary endothelium Glomerular filtration : Glomerular filtration Passive process in which hydrostatic pressure forces fluids & solutes through a memebrane Filtrate formation not consume metabolic energy, so glomerulus is a simple mechanical filter Molecules smaller than 3 nm: pass freely from blood into glomerular capsule (similar concentration in blood & filtrate). Molecules larger than 5nm not enter the tubule (higher concentration in capillaries), so maintain oncotic pressure of glomerular blood & prevents losss of all water into renal tubules Factors Affecting Glomerular Filtration : Factors Affecting Glomerular Filtration Prostaglandins (PGE2 and PGI2) Vasodilators produced in response to sympathetic stimulation and angiotensin II Are thought to prevent renal damage when peripheral resistance is increased Nitric oxide – vasodilator produced by the vascular endothelium Adenosine – vasoconstrictor of renal vasculature Endothelin – a powerful vasoconstrictor secreted by tubule cells Glomerular Filtration Rate GFR : Glomerular Filtration Rate GFR The amount of filtrate formed in all the renal corpuscles of both kidneys GFR= 125ml/min Homeostasis of the body fluids require that the kidneys maintain a relatively constant GFR Mechanisms regulate GFR : Adjusting blood flow into & out of the glomerulus Altering the glomerular capillary surface area available for filtration Mechanisms control GFR Renal autoregulation (intrinsic control) Extrinsic control (nervous & endocrine) Filtration Pressure and Rate : Filtration Pressure and Rate Net Filtration Pressure = force favoring filtration – forces opposing filtration (glomerular capillary ( capsular hydrostatic pressure hydrostatic pressure) and glomerular capillary osmotic pressure ) Glomerular Filtration Rate directly proportional to the net filtration pressure Filtration Pressure and Rate : Filtration Pressure and Rate Normally the glomerular net filtration pressure is positive causing filtration the forces responsible include hydrostatic pressure and osmotic pressure of plasma and the hydrostatic pressure of the fluid in the glomerular capsule Control of Filtration Rate : Control of Filtration Rate Primarily three mechanisms are responsible for keeping the GFR constant Increased sympathetic impulses decrease GFR by causing afferent arterioles to constrict Renin-angiotensin system Autoregulation Renin-Angiotensin system Renal autoregulation : Renal autoregulation Work in blood pressure of 80-180 Include Myogenic mechanism: ? Bp ? stretching of smooth muscle fibres in the wall of afferent arterioles ? ? renal blood flow?? GFR ? contraction of smooth muscle fibres in the wall of afferent arterioles ??renal blood flow ? ?GFR Tubuloglomerular feedback: ? Bp? PCT & Loop of Henle have less time to reabsorb Na+, Cl- & water? macula densa cells detect these changes ? inhibit release of NO from JGA (NO cause vasodilation)? afferent arterioles constrict ??renal blood flow ? ?GFR Autoregulation of High Filtration Pressure : Autoregulation of High Filtration Pressure 14-13 Neural regulation : Neural regulation Blood vessels of kidney supplied by sympathetic ANS fibres which secrete norepinphrine norepinphrine? vasoconstriction (specially in afferent arterioles) ? ?GFR Low stimulation? afferent & efferent arterioles relax &dilated ? renal autoregulation Moderate stimulation ?constriction of both afferent & efferent arterioles ? ?GFR slightly Strong stimulation ? vasoconstriction of afferent arterioles predominates ??renal blood flow ? ?GFR Lowering renal blood flow Reduce urine output & conserve blood volume Permit greater blood flow to other body tissues Hormonal regulation : Hormonal regulation 2 hormones: Angiotensin II??GFR Arterial natriuretic peptide ANP ??GFR Arterial Natriuretic Peptide ANP : Arterial Natriuretic Peptide ANP ?blood volume ?stretching of atria ? secretion of ANP? relaxation of glomerular mesangial cells ??capillary surface area available for filtration ??GFR Tubular Reabsorption : Tubular Reabsorption Transports substances from the glomerular filtrate into the blood within the peritubular capillary Peritubular capillaries : Peritubular capillaries They arise from the efferent arterioles draining the glomeruli cling closely to adjacent renal tubules Empty into venules They are low-pressure, porous capillaries that readily absorb solutes & water from the tubule cells as these substances reclaimed from the filtrate Have low hydrostatic pressure Have high colloid osmotic (oncotic) pressure Reabsorption and secretion : Reabsorption and secretion Fluid entering PCT in ½ hour is greater than the total blood volume Reabsorption is the return of most of the filtered water & many filtered solutes to blood stream Reabsorption is the 2nd basic function of nephron & collecting duct Conversion of the glomerular filtrate to urine involves the removal and addition of chemicals by tubular reabsorption and secretion Accomplished ( complete) via diffusion, osmosis, and carrier-mediated transport Reabsorption and secretion : Reabsorption and secretion Epithelial cells of renal tubule & collecting ducts carry out re-absorption Cells of the PCT reabsorb 60-70% of the filtrate volume Solutes reabsorbed by both active & passive transports include Glucose, amino acids, urea Ions as Na+, K+, Ca2+, HCO3? , & HPO42- Reabsorbed materials enter the peritubular fluid and diffuse into the preitubular capillaries Reabsorption and secretion : Reabsorption and secretion 3rd function of nephron & collecting duct is tubular secretion Tubular Secretion is the transfer of materials from blood & tubular cells into tubular fluid H+, K+, ammonium ion NH4+ , creatinine Certain drugs: pencilline Tubular Secretion has 2 imp. Functions H+ secretion help control blood pH Secretion of other substances help eliminate them from body Absorptive Capabilities of Renal Tubules and Collecting Ducts : Absorptive Capabilities of Renal Tubules and Collecting Ducts Substances reabsorbed in PCT include: Sodium, all nutrients, cations, anions, and water Urea and lipid-soluble solutes Small proteins Loop of Henle reabsorbs: H2O, Na+, Cl?, K+ in the descending limb Ca2+, Mg2+, and Na+ in the ascending limb Absorptive Capabilities of Renal Tubules and Collecting Ducts : Absorptive Capabilities of Renal Tubules and Collecting Ducts DCT absorbs: Ca2+, Na+, H+, K+, and water HCO3? and Cl? Collecting duct absorbs: Water and urea Reabsorption Routes : Reabsorption Routes Two routes of reabsorption Transcellular route – substances pass through the cells cytoplasm and out the base of the ET Paracellular route – substances pass between the cells Routes of Water and Solute Reabsorption : Routes of Water and Solute Reabsorption Figure 25.11 Transport Mechanisms : Transport Mechanisms Active or passive Primary active transport: energy from ATP hydrolysis used to pump a substance across a mem. Secondary active transport: energy stored in ion’s electrochemical gradient drives another substance across a mem. Symporters: mem. Proteins move 2 or more substances in the same direction across a mem. Antiporters: mem. Proteins move 2 or more substances in the opposite direction across a mem. Transport Mechanisms : Transport Mechanisms Obligatory water reabsorption: water re-absorbed with solutes from tubular fluid 90% PCT Facultative water reabsorption: ADH 10% Collecting ducts Functions of the PCT : Functions of the PCT The PCT is very long and its cells contain many mitochondria that supply ATP for active transport. The brush border increase surface area for reabsorption Two routes of reabsorption Transcellular route – substances pass through the cells cytoplasm and out the base of the ET Paracellular route – substances pass between the cells Most absorptive process involve Na+ Tubular Reabsorption : Tubular Reabsorption A transepithelial process where by most tubule contents are returned to the blood Transported substances move through three membranes Luminal and basolateral membranes of tubule cells Endothelium of peritubular capillaries. Only Ca2+, Mg2+, K+, and some Na+ are reabsorbed via paracellular pathways All organic nutrients are reabsorbed Water and ion reabsorption is hormonally controlled Reabsorption may be an active (requiring ATP) or passive process Sodium Reabsorption: Primary Active Transport : Sodium Reabsorption: Primary Active Transport Sodium reabsorption is almost always by active transport Na+ enters the tubule cells at the luminal membrane Is actively transported out of the tubules by a Na+-K+ ATPase pump. From there it moves to peritubular capillaries due to: Low hydrostatic pressure High osmotic pressure of the blood Na+ reabsorption provides the energy and the means for reabsorbing most other solutes Reabsorption by PCT Cells : Reabsorption by PCT Cells Filtered glucose, AA, lactic acids, water-soluble vitamins, all other nutrients are completely reabsorbed by Na+ Symporters Na+/H+ antiporters Reabsorption by PCT Cells : Reabsorption by PCT Cells Figure 25.12 Reabsorption by PCT Cells : Reabsorption by PCT Cells Active pumping of Na+ drives reabsorption of: Water by osmosis Cations and fat-soluble substances by diffusion Organic nutrients and selected cations by secondary active transport Reabsorption in the Loop of Henle : Reabsorption in the Loop of Henle Tubular fluid osmolarity is close to blood osmolarity Loop of Henle reabsorbs: H2O, Na+, Cl?, K+ in the descending limb Ca2+, Mg2+, and Na+ in the ascending limb reabsorption of water is not automatically Apical mem. of cells in thick ascending limb have Na+, K+, 2Cl? symporters most K+ moves down its conc. back into tubular fluid This leave blood & interstitial fluid with negative charges? reabsorption of cations Ca2+, Mg2+, K+ and Na+ via Para cellular route Ions reabsorbed in ascending limb but not water? tubular fluid osmolarity decrease Reabsorption in DCT : Reabsorption in DCT DCT absorbs: Ca2+, Na+, H+, K+, and water HCO3? and Cl? Na+/Cl? symporters in the apical mem. Na+/ K+ pumps & Cl? leakage channels in basolateral mem. ?peritubular capillaries DCT is major site where PTH stimulate reabsorption of Ca2+ 10-15% of filtered water Reabsorption & secretion in the Collecting Duct : Reabsorption & secretion in the Collecting Duct 90-95% of filtered solutes & water Collecting duct absorbs: Water and urea 2 types of cells Principle cells reabsorb Na+ & secret K+ Intercalated cells reabsorb K+ & HCO3? & secret H+ Na+ passes through apical cells via Na+ leakage channels Principle cells secret variable amounts of K+ K+ leakage channels in apical & basolateral mem.? K+ moves down its conc. Into tubular fluid? main source of K+ excreted in the urine Nonreabsorbed Substances : Nonreabsorbed Substances A transport maximum (Tm): Reflects the number of carriers in the renal tubules available Exists for nearly every substance that is actively reabsorbed When the carriers are saturated, excess of that substance is excreted Nonreabsorbed Substances : Nonreabsorbed Substances Substances are not reabsorbed if they: Lack carriers Are not lipid soluble Are too large to pass through membrane pores Urea, creatinine, and uric acid are the most important nonreabsorbed substances Tubular Secretion : Tubular Secretion Essentially reabsorption in reverse, where substances move from peritubular capillaries or tubule cells into filtrate Tubular secretion is important for: Disposing of substances not already in the filtrate Eliminating undesirable substances such as urea and uric acid Ridding the body of excess potassium ions Controlling blood pH Hormonal Regulation of Tubular Reabsorption & Tubular Secretion : Hormonal Regulation of Tubular Reabsorption & Tubular Secretion 4 hormones water & Na+, Cl?, K+ reabsorption Angiotensin II & aldosterone regulate electrolyte reabsorption ADH regulate water reabsorption ANP inhibit both electrolytes & water reabsorption Renin-Angiotensin Mechanism : Renin-Angiotensin Mechanism A reduction in afferent arteriole pressure triggers the JG cells release renin Renin acts on angiotensinogen to release angiotensin I Angiotensin I is converted to angiotensin II Angiotensin II: Causes mean arterial pressure to rise Stimulates the adrenal cortex to release aldosterone As a result, both systemic and glomerular hydrostatic pressure rise Slide 50: http://www.cvphysiology.com/Blood%20Pressure/BP015.htm Slide 51: Figure 25.10 ADH and urine volume : ADH and urine volume The permeability of the wall of the collecting duct varies under the influence of antidiuretic hormone (ADH). ADH is released by the posterior pituitary in response to increased osmotic pressure (decreased water or increased solutes in blood). When ADH reaches the kidney, it increases the permeability of the epithelial linings of the distal convoluted tubule and collecting duct to water, and water moves rapidly out of these segments, eventually into the blood, by osmosis (water is reabsorbed). ADH and urine volume : ADH and urine volume Within principle cells, vesicles containing a water channel proteins called aquaporin-2 ADH ? aquaporin-2 insertion in the in the apical mem.? increase permeability of principle cells to water Consequently, urine volume falls, and urine concentrates soluble wastes and other substances in minimal water. Concentrated urine minimizes loss of body fluids when dehydration is likely. If the osmotic pressure of the blood decreases, ADH is not released and water stays in the collecting duct, leaves as part of the urine. The Effects of ADH on the DCT and Collecting Ducts : Figure 26.15a, b The Effects of ADH on the DCT and Collecting Ducts Aldosterone and urine concentration : Aldosterone and urine concentration Aldosterone is a steroid secreted by the adrenal cortex It is secreted when blood sodium falls or if blood potassium rises It is also secreted if BP drops (indirectly through the release of renin-angiotensin II that promotes aldosterone secretion) Aldosterone secreted – increased tubular reabsorption of Na+ in exchange for secretion of K+ ions – water follow Net effect is that the body retains NaCl and water and urine volume reduced The retention of salt and water help to maintain blood pressure and volume Atrial natriuretic peptide (ANP) and urine volume : Atrial natriuretic peptide (ANP) and urine volume Secreted from the atrial myocardium in response to high BP, increase in blood volume Has 4 actions that result in the excretion of more salt and water in the urine: Dilate afferent arteriole and constricts efferent – increase GFR (more blood flow and higher GHP) Antagonized angiotensin-aldosterone mechanism by inhibiting both renin and aldosterone secretion Inhibits ADH Inhibits NaCl reabsorption by the collecting ducts Sodium and Water Reabsorption : Sodium and Water Reabsorption osmosis reabsorbs water in response to active transport reabsorbing sodium and other solutes in the proximal portion of the renal tubule Countercurrent Mechanism : Countercurrent Mechanism Interaction between the flow of filtrate through the loop of Henle (countercurrent multiplier) and the flow of blood through the vasa recta blood vessels (countercurrent exchanger) The solute concentration in the loop of Henle ranges from 300 mOsm to 1200 mOsm Dissipation of the medullary osmotic gradient is prevented because the blood in the vasa recta equilibrates with the interstitial fluid Osmotic Gradient in the Renal Medulla : Osmotic Gradient in the Renal Medulla Figure 25.13 Loop of Henle: Countercurrent Multiplier : Loop of Henle: Countercurrent Multiplier The descending loop of Henle: Is relatively impermeable to solutes Is permeable to water The ascending loop of Henle: Is permeable to solutes Is impermeable to water Collecting ducts in the deep medullary regions are permeable to urea Loop of Henle: Countercurrent Exchanger : Loop of Henle: Countercurrent Exchanger The vasa recta is a countercurrent exchanger that: Maintains the osmotic gradient Delivers blood to the cells in the area Loop of Henle: Countercurrent Mechanism : Loop of Henle: Countercurrent Mechanism Figure 25.14 Formation of Dilute Urine : Formation of Dilute Urine Filtrate is diluted in the ascending loop of Henle Dilute urine is created by allowing this filtrate to continue into the renal pelvis This will happen as long as antidiuretic hormone (ADH) is not being secreted Formation of Dilute Urine : Formation of Dilute Urine Collecting ducts remain impermeable to water; no further water reabsorption occurs Sodium and selected ions can be removed by active and passive mechanisms Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma) Formation of Concentrated Urine : Formation of Concentrated Urine Antidiuretic hormone (ADH) inhibits diuresis This equalizes the osmolality of the filtrate and the interstitial fluid In the presence of ADH, 99% of the water in filtrate is reabsorbed Formation of Concentrated Urine : Formation of Concentrated Urine ADH-dependent water reabsorption is called facultative water reabsorption ADH is the signal to produce concentrated urine ADH increase the permeability of the principle cells in the collecting duct. Principle cells contain water channel protein (aquaporin-2), ADH stimulate insertion of the aquaporin-2 containing vesicles into the apical membrane via exocytosis? increase permeability of principle cells ? water molecules move more rapidly from tubular fluid into the cells. The kidneys’ ability to respond depends upon the high medullary osmotic gradient Formation of Dilute and Concentrated Urine : Formation of Dilute and Concentrated Urine Figure 25.15a, b Diuretics : Diuretics Chemicals that enhance the urinary output include: Any substance not reabsorbed Substances that exceed the ability of the renal tubules to reabsorb it Substances that inhibit Na+ reabsorption Diuretics : Diuretics Osmotic diuretics include: High glucose levels – carries water out with the glucose Alcohol – inhibits the release of ADH Caffeine and most diuretic drugs – inhibit sodium ion reabsorption Lasix and Diuril – inhibit Na+-associated symporters Summary of Nephron Function : Summary of Nephron Function Figure 25.16 Renal Clearance : Renal Clearance The volume of plasma that is cleared of a particular substance in a given time Renal clearance tests are used to: Determine the GFR Detect glomerular damage Follow the progress of diagnosed renal disease Renal Clearance : Renal Clearance RC = UV/P RC = renal clearance rate U= concentration (mg/ml) of the substance in urine V = flow rate of urine formation (ml/min) P = concentration of the same substance in plasma Micturition (Voiding or Urination) : Micturition (Voiding or Urination) The act of emptying the bladder Distension of bladder walls initiates spinal reflexes that: Stimulate contraction of the external urethral sphincter Inhibit the detrusor muscle and internal sphincter (temporarily) Voiding reflexes: Stimulate the detrusor muscle to contract Inhibit the internal and external sphincters Micturition (Voiding or Urination) : Micturition (Voiding or Urination) Physical Characteristics of Urine : Physical Characteristics of Urine Color and transparency Clear, pale to deep yellow (due to urochrome) Concentrated urine has a deeper yellow color Drugs, vitamin supplements, and diet can change the color of urine Cloudy urine may indicate infection of the urinary tract Physical Characteristics of Urine : Physical Characteristics of Urine Odor Fresh urine is slightly aromatic Standing urine develops an ammonia odor Some drugs and vegetables (asparagus) alter the usual odor Physical Characteristics of Urine : Physical Characteristics of Urine pH Slightly acidic (pH 6) with a range of 4.5 to 8.0 Diet can alter pH Specific gravity Ranges from 1.001 to 1.035 Is dependent on solute concentration Chemical Composition of Urine : Chemical Composition of Urine Urine is 95% water and 5% solutes Nitrogenous wastes include urea, uric acid, and creatinine Other normal solutes include: Sodium, potassium, phosphate, and sulfate ions Calcium, magnesium, and bicarbonate ions Abnormally high concentrations of any urinary constituents may indicate pathology Question : Question Mention characteristic properties of Peritubular capillaries? 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urinary system.3 mohanad Download Post to : URL : Related Presentations : Share Add to Flag Embed Email Send to Blogs and Networks Add to Channel Uploaded from authorPOINT lite Insert YouTube videos in PowerPont slides with aS Desktop Copy embed code: (To copy code, click on the text box) Embed: URL: Thumbnail: WordPress Embed Customize Embed The presentation is successfully added In Your Favorites. Views: 2368 Category: Education License: All Rights Reserved Like it (0) Dislike it (0) Added: April 07, 2009 This Presentation is Public Favorites: 0 Presentation Description No description available. Comments Posting comment... By: yilian (7 month(s) ago) Its effective Saving..... Post Reply Close Saving..... Edit Comment Close By: ekegg (12 month(s) ago) good Saving..... Post Reply Close Saving..... Edit Comment Close Premium member Presentation Transcript Urinary system : Urinary system SMS 1113 Dr. Mohanad R. Alwan Nephron Function : Nephron Function Filtration Selective Reabsorption Tubular Secretion Urine formation : Urine formation Nephrons remove wastes from the blood and regulate water and electrolyte concentrations urine is the final product of the processes of: glomerular filtration tubular reabsorption tubular secretion Slide 4: 14-6 Slide 5: 14-7 Filtration : Filtration Analysis of Glomerular Capillary Dynamics Blood Pressure =55.0 mm Hg O (vs 35 normally) Plasma Coll O.P. =30.0 mm Hg I BC Hydrostatic P. =15.0 mm Hg I 10.0 mm Hg O = Filtration Pressure Regulation of Filtration Pressure : Regulation of Filtration Pressure 14-10 Regulation of Filtration Pressure : Regulation of Filtration Pressure 14-11 Urine formation : Urine formation Urine formation include 3 basic steps Glomerular filtration: 1st step of urine production Water & most solutes in blood plasma move across the wall of glomerular capillaries into the glomerular capsule & then into renal tubule Tubular absorption: when filtered fluid flows along the renal tubule & through collecting duct, tubule cells reabsorb 99% of filtered water & useful solutes Re-absorped water & solutes return to blood through peritubular capillaries & vasa recta Tubular secretion: when filtered fluid flows through renal tubule& collecting ducts, tubule & duct cells secrete other materials (wastes, drugs, excess ions) into the filtered fluid Urine formation : Urine formation Glomerular Filtration substances move from blood to glomerular capsule Tubular Reabsorption substances move from renal tubules into blood of peritubular capillaries glucose, water, urea, proteins, creatine amino, lactic, citric, and uric acids phosphate, sulfate, calcium, potassium, and sodium ions Tubular Secretion substances move from blood of peritubular capillaries into renal tubules drugs and ions Glomerular Filtration : Glomerular Filtration Rate (GFR): 120 mL/min (normal) Substances “Filtered”: water, electrolytes (Na, K, etc.), sugars (glucose), nitrogenous waste (urea, creatinine) Substances “Excluded”: Substances of size > 70 kDa Plasma protein bound substances Glomerular Filtration : Glomerular Filtration Glomerular Filtration : Glomerular Filtration The first step in urine formation is filtration of substances out of the glomerular capillaries into the glomerular capsule Glomerular filtrate passes through the fenestrae of the capillary endothelium Glomerular filtration : Glomerular filtration Passive process in which hydrostatic pressure forces fluids & solutes through a memebrane Filtrate formation not consume metabolic energy, so glomerulus is a simple mechanical filter Molecules smaller than 3 nm: pass freely from blood into glomerular capsule (similar concentration in blood & filtrate). Molecules larger than 5nm not enter the tubule (higher concentration in capillaries), so maintain oncotic pressure of glomerular blood & prevents losss of all water into renal tubules Factors Affecting Glomerular Filtration : Factors Affecting Glomerular Filtration Prostaglandins (PGE2 and PGI2) Vasodilators produced in response to sympathetic stimulation and angiotensin II Are thought to prevent renal damage when peripheral resistance is increased Nitric oxide – vasodilator produced by the vascular endothelium Adenosine – vasoconstrictor of renal vasculature Endothelin – a powerful vasoconstrictor secreted by tubule cells Glomerular Filtration Rate GFR : Glomerular Filtration Rate GFR The amount of filtrate formed in all the renal corpuscles of both kidneys GFR= 125ml/min Homeostasis of the body fluids require that the kidneys maintain a relatively constant GFR Mechanisms regulate GFR : Adjusting blood flow into & out of the glomerulus Altering the glomerular capillary surface area available for filtration Mechanisms control GFR Renal autoregulation (intrinsic control) Extrinsic control (nervous & endocrine) Filtration Pressure and Rate : Filtration Pressure and Rate Net Filtration Pressure = force favoring filtration – forces opposing filtration (glomerular capillary ( capsular hydrostatic pressure hydrostatic pressure) and glomerular capillary osmotic pressure ) Glomerular Filtration Rate directly proportional to the net filtration pressure Filtration Pressure and Rate : Filtration Pressure and Rate Normally the glomerular net filtration pressure is positive causing filtration the forces responsible include hydrostatic pressure and osmotic pressure of plasma and the hydrostatic pressure of the fluid in the glomerular capsule Control of Filtration Rate : Control of Filtration Rate Primarily three mechanisms are responsible for keeping the GFR constant Increased sympathetic impulses decrease GFR by causing afferent arterioles to constrict Renin-angiotensin system Autoregulation Renin-Angiotensin system Renal autoregulation : Renal autoregulation Work in blood pressure of 80-180 Include Myogenic mechanism: ? Bp ? stretching of smooth muscle fibres in the wall of afferent arterioles ? ? renal blood flow?? GFR ? contraction of smooth muscle fibres in the wall of afferent arterioles ??renal blood flow ? ?GFR Tubuloglomerular feedback: ? Bp? PCT & Loop of Henle have less time to reabsorb Na+, Cl- & water? macula densa cells detect these changes ? inhibit release of NO from JGA (NO cause vasodilation)? afferent arterioles constrict ??renal blood flow ? ?GFR Autoregulation of High Filtration Pressure : Autoregulation of High Filtration Pressure 14-13 Neural regulation : Neural regulation Blood vessels of kidney supplied by sympathetic ANS fibres which secrete norepinphrine norepinphrine? vasoconstriction (specially in afferent arterioles) ? ?GFR Low stimulation? afferent & efferent arterioles relax &dilated ? renal autoregulation Moderate stimulation ?constriction of both afferent & efferent arterioles ? ?GFR slightly Strong stimulation ? vasoconstriction of afferent arterioles predominates ??renal blood flow ? ?GFR Lowering renal blood flow Reduce urine output & conserve blood volume Permit greater blood flow to other body tissues Hormonal regulation : Hormonal regulation 2 hormones: Angiotensin II??GFR Arterial natriuretic peptide ANP ??GFR Arterial Natriuretic Peptide ANP : Arterial Natriuretic Peptide ANP ?blood volume ?stretching of atria ? secretion of ANP? relaxation of glomerular mesangial cells ??capillary surface area available for filtration ??GFR Tubular Reabsorption : Tubular Reabsorption Transports substances from the glomerular filtrate into the blood within the peritubular capillary Peritubular capillaries : Peritubular capillaries They arise from the efferent arterioles draining the glomeruli cling closely to adjacent renal tubules Empty into venules They are low-pressure, porous capillaries that readily absorb solutes & water from the tubule cells as these substances reclaimed from the filtrate Have low hydrostatic pressure Have high colloid osmotic (oncotic) pressure Reabsorption and secretion : Reabsorption and secretion Fluid entering PCT in ½ hour is greater than the total blood volume Reabsorption is the return of most of the filtered water & many filtered solutes to blood stream Reabsorption is the 2nd basic function of nephron & collecting duct Conversion of the glomerular filtrate to urine involves the removal and addition of chemicals by tubular reabsorption and secretion Accomplished ( complete) via diffusion, osmosis, and carrier-mediated transport Reabsorption and secretion : Reabsorption and secretion Epithelial cells of renal tubule & collecting ducts carry out re-absorption Cells of the PCT reabsorb 60-70% of the filtrate volume Solutes reabsorbed by both active & passive transports include Glucose, amino acids, urea Ions as Na+, K+, Ca2+, HCO3? , & HPO42- Reabsorbed materials enter the peritubular fluid and diffuse into the preitubular capillaries Reabsorption and secretion : Reabsorption and secretion 3rd function of nephron & collecting duct is tubular secretion Tubular Secretion is the transfer of materials from blood & tubular cells into tubular fluid H+, K+, ammonium ion NH4+ , creatinine Certain drugs: pencilline Tubular Secretion has 2 imp. Functions H+ secretion help control blood pH Secretion of other substances help eliminate them from body Absorptive Capabilities of Renal Tubules and Collecting Ducts : Absorptive Capabilities of Renal Tubules and Collecting Ducts Substances reabsorbed in PCT include: Sodium, all nutrients, cations, anions, and water Urea and lipid-soluble solutes Small proteins Loop of Henle reabsorbs: H2O, Na+, Cl?, K+ in the descending limb Ca2+, Mg2+, and Na+ in the ascending limb Absorptive Capabilities of Renal Tubules and Collecting Ducts : Absorptive Capabilities of Renal Tubules and Collecting Ducts DCT absorbs: Ca2+, Na+, H+, K+, and water HCO3? and Cl? Collecting duct absorbs: Water and urea Reabsorption Routes : Reabsorption Routes Two routes of reabsorption Transcellular route – substances pass through the cells cytoplasm and out the base of the ET Paracellular route – substances pass between the cells Routes of Water and Solute Reabsorption : Routes of Water and Solute Reabsorption Figure 25.11 Transport Mechanisms : Transport Mechanisms Active or passive Primary active transport: energy from ATP hydrolysis used to pump a substance across a mem. Secondary active transport: energy stored in ion’s electrochemical gradient drives another substance across a mem. Symporters: mem. Proteins move 2 or more substances in the same direction across a mem. Antiporters: mem. Proteins move 2 or more substances in the opposite direction across a mem. Transport Mechanisms : Transport Mechanisms Obligatory water reabsorption: water re-absorbed with solutes from tubular fluid 90% PCT Facultative water reabsorption: ADH 10% Collecting ducts Functions of the PCT : Functions of the PCT The PCT is very long and its cells contain many mitochondria that supply ATP for active transport. The brush border increase surface area for reabsorption Two routes of reabsorption Transcellular route – substances pass through the cells cytoplasm and out the base of the ET Paracellular route – substances pass between the cells Most absorptive process involve Na+ Tubular Reabsorption : Tubular Reabsorption A transepithelial process where by most tubule contents are returned to the blood Transported substances move through three membranes Luminal and basolateral membranes of tubule cells Endothelium of peritubular capillaries. Only Ca2+, Mg2+, K+, and some Na+ are reabsorbed via paracellular pathways All organic nutrients are reabsorbed Water and ion reabsorption is hormonally controlled Reabsorption may be an active (requiring ATP) or passive process Sodium Reabsorption: Primary Active Transport : Sodium Reabsorption: Primary Active Transport Sodium reabsorption is almost always by active transport Na+ enters the tubule cells at the luminal membrane Is actively transported out of the tubules by a Na+-K+ ATPase pump. From there it moves to peritubular capillaries due to: Low hydrostatic pressure High osmotic pressure of the blood Na+ reabsorption provides the energy and the means for reabsorbing most other solutes Reabsorption by PCT Cells : Reabsorption by PCT Cells Filtered glucose, AA, lactic acids, water-soluble vitamins, all other nutrients are completely reabsorbed by Na+ Symporters Na+/H+ antiporters Reabsorption by PCT Cells : Reabsorption by PCT Cells Figure 25.12 Reabsorption by PCT Cells : Reabsorption by PCT Cells Active pumping of Na+ drives reabsorption of: Water by osmosis Cations and fat-soluble substances by diffusion Organic nutrients and selected cations by secondary active transport Reabsorption in the Loop of Henle : Reabsorption in the Loop of Henle Tubular fluid osmolarity is close to blood osmolarity Loop of Henle reabsorbs: H2O, Na+, Cl?, K+ in the descending limb Ca2+, Mg2+, and Na+ in the ascending limb reabsorption of water is not automatically Apical mem. of cells in thick ascending limb have Na+, K+, 2Cl? symporters most K+ moves down its conc. back into tubular fluid This leave blood & interstitial fluid with negative charges? reabsorption of cations Ca2+, Mg2+, K+ and Na+ via Para cellular route Ions reabsorbed in ascending limb but not water? tubular fluid osmolarity decrease Reabsorption in DCT : Reabsorption in DCT DCT absorbs: Ca2+, Na+, H+, K+, and water HCO3? and Cl? Na+/Cl? symporters in the apical mem. Na+/ K+ pumps & Cl? leakage channels in basolateral mem. ?peritubular capillaries DCT is major site where PTH stimulate reabsorption of Ca2+ 10-15% of filtered water Reabsorption & secretion in the Collecting Duct : Reabsorption & secretion in the Collecting Duct 90-95% of filtered solutes & water Collecting duct absorbs: Water and urea 2 types of cells Principle cells reabsorb Na+ & secret K+ Intercalated cells reabsorb K+ & HCO3? & secret H+ Na+ passes through apical cells via Na+ leakage channels Principle cells secret variable amounts of K+ K+ leakage channels in apical & basolateral mem.? K+ moves down its conc. Into tubular fluid? main source of K+ excreted in the urine Nonreabsorbed Substances : Nonreabsorbed Substances A transport maximum (Tm): Reflects the number of carriers in the renal tubules available Exists for nearly every substance that is actively reabsorbed When the carriers are saturated, excess of that substance is excreted Nonreabsorbed Substances : Nonreabsorbed Substances Substances are not reabsorbed if they: Lack carriers Are not lipid soluble Are too large to pass through membrane pores Urea, creatinine, and uric acid are the most important nonreabsorbed substances Tubular Secretion : Tubular Secretion Essentially reabsorption in reverse, where substances move from peritubular capillaries or tubule cells into filtrate Tubular secretion is important for: Disposing of substances not already in the filtrate Eliminating undesirable substances such as urea and uric acid Ridding the body of excess potassium ions Controlling blood pH Hormonal Regulation of Tubular Reabsorption & Tubular Secretion : Hormonal Regulation of Tubular Reabsorption & Tubular Secretion 4 hormones water & Na+, Cl?, K+ reabsorption Angiotensin II & aldosterone regulate electrolyte reabsorption ADH regulate water reabsorption ANP inhibit both electrolytes & water reabsorption Renin-Angiotensin Mechanism : Renin-Angiotensin Mechanism A reduction in afferent arteriole pressure triggers the JG cells release renin Renin acts on angiotensinogen to release angiotensin I Angiotensin I is converted to angiotensin II Angiotensin II: Causes mean arterial pressure to rise Stimulates the adrenal cortex to release aldosterone As a result, both systemic and glomerular hydrostatic pressure rise Slide 50: http://www.cvphysiology.com/Blood%20Pressure/BP015.htm Slide 51: Figure 25.10 ADH and urine volume : ADH and urine volume The permeability of the wall of the collecting duct varies under the influence of antidiuretic hormone (ADH). ADH is released by the posterior pituitary in response to increased osmotic pressure (decreased water or increased solutes in blood). When ADH reaches the kidney, it increases the permeability of the epithelial linings of the distal convoluted tubule and collecting duct to water, and water moves rapidly out of these segments, eventually into the blood, by osmosis (water is reabsorbed). ADH and urine volume : ADH and urine volume Within principle cells, vesicles containing a water channel proteins called aquaporin-2 ADH ? aquaporin-2 insertion in the in the apical mem.? increase permeability of principle cells to water Consequently, urine volume falls, and urine concentrates soluble wastes and other substances in minimal water. Concentrated urine minimizes loss of body fluids when dehydration is likely. If the osmotic pressure of the blood decreases, ADH is not released and water stays in the collecting duct, leaves as part of the urine. The Effects of ADH on the DCT and Collecting Ducts : Figure 26.15a, b The Effects of ADH on the DCT and Collecting Ducts Aldosterone and urine concentration : Aldosterone and urine concentration Aldosterone is a steroid secreted by the adrenal cortex It is secreted when blood sodium falls or if blood potassium rises It is also secreted if BP drops (indirectly through the release of renin-angiotensin II that promotes aldosterone secretion) Aldosterone secreted – increased tubular reabsorption of Na+ in exchange for secretion of K+ ions – water follow Net effect is that the body retains NaCl and water and urine volume reduced The retention of salt and water help to maintain blood pressure and volume Atrial natriuretic peptide (ANP) and urine volume : Atrial natriuretic peptide (ANP) and urine volume Secreted from the atrial myocardium in response to high BP, increase in blood volume Has 4 actions that result in the excretion of more salt and water in the urine: Dilate afferent arteriole and constricts efferent – increase GFR (more blood flow and higher GHP) Antagonized angiotensin-aldosterone mechanism by inhibiting both renin and aldosterone secretion Inhibits ADH Inhibits NaCl reabsorption by the collecting ducts Sodium and Water Reabsorption : Sodium and Water Reabsorption osmosis reabsorbs water in response to active transport reabsorbing sodium and other solutes in the proximal portion of the renal tubule Countercurrent Mechanism : Countercurrent Mechanism Interaction between the flow of filtrate through the loop of Henle (countercurrent multiplier) and the flow of blood through the vasa recta blood vessels (countercurrent exchanger) The solute concentration in the loop of Henle ranges from 300 mOsm to 1200 mOsm Dissipation of the medullary osmotic gradient is prevented because the blood in the vasa recta equilibrates with the interstitial fluid Osmotic Gradient in the Renal Medulla : Osmotic Gradient in the Renal Medulla Figure 25.13 Loop of Henle: Countercurrent Multiplier : Loop of Henle: Countercurrent Multiplier The descending loop of Henle: Is relatively impermeable to solutes Is permeable to water The ascending loop of Henle: Is permeable to solutes Is impermeable to water Collecting ducts in the deep medullary regions are permeable to urea Loop of Henle: Countercurrent Exchanger : Loop of Henle: Countercurrent Exchanger The vasa recta is a countercurrent exchanger that: Maintains the osmotic gradient Delivers blood to the cells in the area Loop of Henle: Countercurrent Mechanism : Loop of Henle: Countercurrent Mechanism Figure 25.14 Formation of Dilute Urine : Formation of Dilute Urine Filtrate is diluted in the ascending loop of Henle Dilute urine is created by allowing this filtrate to continue into the renal pelvis This will happen as long as antidiuretic hormone (ADH) is not being secreted Formation of Dilute Urine : Formation of Dilute Urine Collecting ducts remain impermeable to water; no further water reabsorption occurs Sodium and selected ions can be removed by active and passive mechanisms Urine osmolality can be as low as 50 mOsm (one-sixth that of plasma) Formation of Concentrated Urine : Formation of Concentrated Urine Antidiuretic hormone (ADH) inhibits diuresis This equalizes the osmolality of the filtrate and the interstitial fluid In the presence of ADH, 99% of the water in filtrate is reabsorbed Formation of Concentrated Urine : Formation of Concentrated Urine ADH-dependent water reabsorption is called facultative water reabsorption ADH is the signal to produce concentrated urine ADH increase the permeability of the principle cells in the collecting duct. Principle cells contain water channel protein (aquaporin-2), ADH stimulate insertion of the aquaporin-2 containing vesicles into the apical membrane via exocytosis? increase permeability of principle cells ? water molecules move more rapidly from tubular fluid into the cells. The kidneys’ ability to respond depends upon the high medullary osmotic gradient Formation of Dilute and Concentrated Urine : Formation of Dilute and Concentrated Urine Figure 25.15a, b Diuretics : Diuretics Chemicals that enhance the urinary output include: Any substance not reabsorbed Substances that exceed the ability of the renal tubules to reabsorb it Substances that inhibit Na+ reabsorption Diuretics : Diuretics Osmotic diuretics include: High glucose levels – carries water out with the glucose Alcohol – inhibits the release of ADH Caffeine and most diuretic drugs – inhibit sodium ion reabsorption Lasix and Diuril – inhibit Na+-associated symporters Summary of Nephron Function : Summary of Nephron Function Figure 25.16 Renal Clearance : Renal Clearance The volume of plasma that is cleared of a particular substance in a given time Renal clearance tests are used to: Determine the GFR Detect glomerular damage Follow the progress of diagnosed renal disease Renal Clearance : Renal Clearance RC = UV/P RC = renal clearance rate U= concentration (mg/ml) of the substance in urine V = flow rate of urine formation (ml/min) P = concentration of the same substance in plasma Micturition (Voiding or Urination) : Micturition (Voiding or Urination) The act of emptying the bladder Distension of bladder walls initiates spinal reflexes that: Stimulate contraction of the external urethral sphincter Inhibit the detrusor muscle and internal sphincter (temporarily) Voiding reflexes: Stimulate the detrusor muscle to contract Inhibit the internal and external sphincters Micturition (Voiding or Urination) : Micturition (Voiding or Urination) Physical Characteristics of Urine : Physical Characteristics of Urine Color and transparency Clear, pale to deep yellow (due to urochrome) Concentrated urine has a deeper yellow color Drugs, vitamin supplements, and diet can change the color of urine Cloudy urine may indicate infection of the urinary tract Physical Characteristics of Urine : Physical Characteristics of Urine Odor Fresh urine is slightly aromatic Standing urine develops an ammonia odor Some drugs and vegetables (asparagus) alter the usual odor Physical Characteristics of Urine : Physical Characteristics of Urine pH Slightly acidic (pH 6) with a range of 4.5 to 8.0 Diet can alter pH Specific gravity Ranges from 1.001 to 1.035 Is dependent on solute concentration Chemical Composition of Urine : Chemical Composition of Urine Urine is 95% water and 5% solutes Nitrogenous wastes include urea, uric acid, and creatinine Other normal solutes include: Sodium, potassium, phosphate, and sulfate ions Calcium, magnesium, and bicarbonate ions Abnormally high concentrations of any urinary constituents may indicate pathology Question : Question Mention characteristic properties of Peritubular capillaries? Slide 80: The End