Counter-Current System Regulation of Renal Functions Assoc. Prof. MUDr. Markéta Bébarová, Ph.D. Department of Physiology Faculty of Medicine, Masaryk University This presentation includes only the most important terms and facts. Its content by itself is not a sufficient source of information required to pass the Physiology exam. Water Transport in Tubules substances with pronounced secretion in comparison with H2O substances with pronounced reabsorption in comparison with H2O GFR 180 l/day UFR 1 l/day UFR 0.5 l/day (1400 mosm/l) up to UFR 23.3 l/day (30 mosm/l) Guyton  Hall. Textbook of Medical Physiology Proximal Tubule Intensive transport of solutes from tubules to interstitium osmotic gradient - water reabsorption Isoosmotic fluid, volume notably decreased (60-70% of solutes and water reabsorbed) Facilitated by water channels (aquaporin 1; not guided by ADH!) Water Transport in Tubules Loop of Henle Hypotonic fluid, volume decreased 1) thin descending part - passive reabsorption of water (osmosis) 2) thick ascending part – impermeable for water, intensive reabsorption of solutes Water Transport in Tubules Distal Tubule Tonicity of the outflowing fluid depends on the actual level of ADH. 1) the first part – analogical to the thick ascending loop of Henle – impermeable for water, reabsorption of solutes (reabsorption of Na+ regulated by aldosteron) 2) the next part – analogical to the cortical part of collecting duct – water reabsorption regulated by ADH (aquaporin 2) Water Transport in Tubules Collecting Duct Tonicity of the outflowing fluid depends on the actual level of ADH. 1) the cortical part – water reabsorption regulated by ADH (aquaporin 2), isotonic intersticium 1) the medullar part – water reabsorption regulated by ADH (aquaporin 2), hypertonic intersticium Water Transport in Tubules Counter-Current System in Kidneys Counter-Current System in Kidneys Guyton  Hall. Textbook of Medical Physiology Hyperosmotic Renal Medulla – Role of Loop of Henle 1) Active transport of Na+, co-transport of Na+ with K+ and Clfrom ascending loop of Henle; gradient even 200 mOsm/l 2) Impermeability of ascending loop of Henle for water diuretics (e.g. furosemid) Counter-Current System in Kidneys 3) Permeability of descending loop of Henle for water Guyton  Hall. Textbook of Medical Physiology Counter-Current System in Kidneys Hyperosmotic Renal Medulla – Role of Loop of Henle 1) Active transport of Na+, co-transport of Na+ with K+ and Clfrom ascending loop of Henle; gradient even 200 mOsm/l 2) Impermeability of ascending loop of Henle for water Guyton  Hall. Textbook of Medical Physiology Hyperosmotic Renal Medulla – Role of Loop of Henle Counter-Current System in Kidneys 1) Active transport of Na+, co-transport of Na+ with K+ and Clfrom ascending loop of Henle; gradient even 200 mOsm/l 2) Impermeability of ascending loop of Henle for water 3) Permeability of descending loop of Henle for water Guyton  Hall. Textbook of Medical Physiology Hyperosmotic Renal Medulla – Role of Loop of Henle Counter-Current System in Kidneys Ganong´s Review of Medical Physiology, 23rd edition Hyperosmotic Renal Medulla – Role of Vasa Recta Counter-Current System in Kidneys Hyperosmotic Renal Medulla – Role of Vasa Recta Guyton  Hall. Textbook of Medical Physiology Counter-Current System in Kidneys Hyperosmotic Renal Medulla – Role of Urea Guyton  Hall. Textbook of Medical Physiology Counter-Current System in Kidneys passive transport following parts of tubulus resistant to urea reabsorption facilitated diffusion (through UT-A1 regulated by ADH) Water Diuresis - after drinking of a higher amount of hypotonic fluid - drinking itself  slightly ↓ ADH secretion - water reabsorption  ↓ plasma osmolarity – osmoreceptors in the hypothalamus  notable ↓ ADH secretion  ↓ water reabsorption in tubulus  ↑ diuresis Water Intoxication Water Diuresis - the water intake per time > the amount of water which can be excreted (maximal diuresis ~16 ml/min) -  cellular edema, symptoms of water intoxication - iatrogenic Osmotic Diuresis - induced by presence of non-absorbed osmotically active solutes in renal tubules (e.g. glucose diabetes mellitus) - non-absorbed solutes in the proximal tubule  osmotic effect – retention of water in the tubulus - ↓ transepithelial gradient for Na+  inhibition of Na+ reabsorption in the proximal tubule  Na+ retained in the tubule ~ further osmotic load  further retaining of water in the tubule Osmotic Diuresis - more isotonic fluid with higher total amount of Na+ into the loop of Henle  ↓ reabsorption of solutes  ↓ hypertonicity of the renal medulla - more fluid flows through other parts of tubulus + ↓ hypertonicity of the renal medulla  ↓ water reabsorption in the collecting duct  ↑ diuresis, urine with an increased amount of solutes Regulation of Renal Functions Regulation of Renal Blood Flow Regulation of Renal Blood Flow 1) Myogenic Autoregulation 2) Neural Regulation 3) Humoral Regulation Ganong´s Review of Medical Physiology, 23rd edition - dominates - provides stable renal activity by maintaining stable blood flow at varying systemic pressure Regulation of Renal Blood Flow 1) Myogenic Autoregulation 2) Neural Regulation - conformed to demands of systemic circulation - sympathetic system - NE light exertion (both emotional and physical) + upright body posture   renal blood flow but without  GFR higher  of sympathetic tone - during anesthesia and pain - GFR may already  Regulation of Renal Blood Flow in healthy people – minor impact 3) Humoral Regulation - contribute to regulation of systemic BP and regulation of body fluids - NE, E (from the adrenal medulla) Regulation of Renal Blood Flow constriction of aff. and eff. arterioles   renal blood flow and GFR (small impact with the exception of serious conditions, for example serious bleeding) 3) Humoral Regulation Regulation of Renal Blood Flow - endothelin constriction of aff. and eff. arterioles   renal blood flow and GFR released locally from the impaired endothel (physiological impact - hemostasis; pathologically increased levels at the toxemia of pregnancy, acute renal failure, chronic uremia) - contribute to regulation of systemic BP and regulation of body fluids 3) Humoral Regulation - NO Regulation of Renal Blood Flow - prostanglandins (PGE2, PGI2), bradykinin continual basal production  vasodilation  stable renal blood flow and GFR  vasodilation minor impact under physiological conditions non-steroidal anti-inflammatory agents during stress! - contribute to regulation of systemic BP and regulation of body fluids 3) Humoral Regulation - Renin-Angiotensine System Regulation of Renal Blood Flow - contribute to regulation of systemic BP and regulation of body fluids Ganong´s Review of Medical Physiology, 23rd edition Renin-Angiotensine System vasoconstriction (more in eff. a.) thirst, ADH  Na+ in plasma  blood pressure  activity of sympathicus ( rec.) Regulation of Renal Blood Flow ↓ renal blood flow but  GFR (usually during  BP or fluid depletion – prevention of  GFR +  tubular reabsorption of Na+ and water due to  Pc in peritubular capillaries) Regulation of Renal Blood Flow Tubuloglomerular Feedback 3) Humoral Regulation Ganong´s Review of Medical Physiology, 23rd edition Guyton  Hall. Textbook of Medical Physiology Regulation of Renal Functions Regulation of Glomerular Filtration Regulation of Tubular Reabsorption GFR = Kf  net filtration pressure GFR = Kf  (PG + πB – PB – πG) Regulation of Glomerular Filtration • control of the glomerular filtration pressure: constriction of vas aff.   glomerular pressure   filtration constriction of vas eff.   glomerular pressure   filtration 1) Local Regulation 2) Neural Regulation 3) Humoral Regulation 1) Local Regulation Regulation of Tubular Reabsorption Glomerulotubular Balance - controls balance between the glomerular filtration and tubular reabsorption Regulation of Tubular Reabsorption Physical Forces in Peritubular Capillaries and in Renal Intersticium 1) Local Regulation TRR = Kf  net reabsorptive force - ↑ Kf  ↑ TRR and vice versaKf - rather stable under physiological conditions Regulation of Tubular Reabsorption 1) Local Regulation Physical Forces in Peritubular Capillaries and in Renal Intersticium TRR = Kf  net reabsorptive force - BP (↑ BP  ↑ Pc  ↓ TRR)Pc - resistance of aff. and eff. arterioles πc - fitration fraction (↑ FF  ↑ πc  ↑ TRR) - π in plasma Regulation of Tubular Reabsorption Physical Forces in Peritubular Capillaries and in Renal Intersticium 1) Local Regulation Guyton  Hall. Textbook of Medical Physiology Regulation of Tubular Reabsorption Physical Forces in Peritubular Capillaries and in Renal Intersticium – changes in intersticium (Pif, πif) 1) Local Regulation Guyton  Hall. Textbook of Medical Physiology ↑ Pif ↓ πif ↑ reabsorption  ↓ Pif a ↑πif  ↓ backleak Regulation of Tubular Reabsorption Pressure Natriuresis and Pressure Diuresis 1) Local Regulation - increased excretion of salt and water at ↑ BP (physiologically slight effect on diuresis autoregulation vs. impaired autoregulation at renal diseases) - mechanisms: ↑ GFR ↓ TRR ↓ formation of angiotensine II (↑ BP  slight ↑ Pc  ↑ Pif  ↑ backleak  ↓ TRR) Regulation of Tubular Reabsorption 2) Neural Regulation Sympathicus - small ↑ of its activity (α-rec. in epithelia):  constriction of aff. and eff. arterioles  ↓ renal blood flow  ↓ Pc  ↑ TRR directly through ↑ reabsorption of Na+ - notable ↑ of its activity - indirectly:  ↑ reabsorption of salt and water Regulation of Tubular Reabsorption 3) Hormonal Regulation - impact – separate regulation of reabsorption/excretion of particular solutes (other mechanisms are nonspecific – influence the total TRR!) Aldosteron Angiotensine II Natriuretic peptides (namely ANP) Antidiuretic hormone Parathormone Urodilatin (renal NP) Regulation of Tubular Reabsorption 3) Hormonal Regulation Aldosteron Angiotensine II Regulation of Tubular Reabsorption Natriuretic peptides increased tension of atrial cardiomyocytes  ↑ secretion of ANP:  ↓ secretion of renin  ↓ angiotensine II  ↓ TRR (congestive heart failure)  ↓ reabsorption of salt and water directly (namely in the collecting ducts) 3) Hormonal Regulation Regulation of Tubular Reabsorption Antidiuretic hormone (ADH) - controls excretion of water ↑ osmolality of plasma (osmoreceptors)  ↑ secretion of ADH – V2 receptors  water channels (aquaporins 2)  ↑ reabsorption of water by osmosis 3) Hormonal Regulation Regulation of Tubular Reabsorption Parathormone - controls excretion of Ca2+ ↓ calcemia  ↑ secretion of parathormone:  ↑ tubular reabsorption of Ca2+ (namely in the distal tubule)  ↓ tubular reabsorption of phosphate in the proximal tubule  ↑ tubular reabsorption of Mg2+ in the loop of Henle 3) Hormonal Regulation Filling and emptying of the bladder cystometrogram