Tubular Processing - Warwick PDF

Tubular Processing Dr Mark Richards [email protected] Acknowledgements to Dr Nick Hopcroft & Dr Jamie Roebuck Learning Outcomes By the end of this session, you should be able to: 1. Describe the role of the kidneys in controlling the volume and compos...

Tubular Processing Dr Mark Richards [email protected] Acknowledgements to Dr Nick Hopcroft & Dr Jamie Roebuck Learning Outcomes By the end of this session, you should be able to: 1. Describe the role of the kidneys in controlling the volume and composition of body fluid 2. Define tubular reabsorption and tubular secretion and explain their role in urine formation and body fluid composition 3. Describe the renal handling of filtered glucose and amino acids  Urine Formation 1 The nephron is the functional unit of the kidney Three main processes performed by nephron:- 1. Filtration 2. Reabsorption 3. Secretion Urinary excretion of any substance reflects the sum of these processes Urinary excretion rate = Filtration rate + Secretion rate – Reabsorption rate LO: 1 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323597128000266#hl00003 Image: Guyton & Hall Textbook of Medical Physiology (13e) - Hall Urine Formation 2 Different substances handled in different ways by the kidney High rate of filtration needed to help clear waste products efficiently (180 litres filtrate/day) Filtering ‘crude’ process Need tubular processing to fine tune volume and composition of urine and to avoid huge fluid and solute losses Reabsorption more important than secretion for most substances in determining the final urinary excretion LO: 1 rate Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323597128000266#hl00003 Image: Guyton & Hall Textbook of Medical Physiology (13e) - Hall Tubular Reabsorption Tubular reabsorption is: 1. Quantitatively large 2. Highly selective (allows independent regulation of solute excretion) LO: 1, 2 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B978032359712800028X#hl00006 Image: Guyton & Hall Textbook of Medical Physiology (12e) - Hall General Mechanisms 1 Tubular reabsorption utilises passive and active transport mechanisms to move fluid and solutes from tubule lumen to peritubular capillary Luminal and basal surfaces of tubule epithelial cells have different transporters allowing concentration gradients to be established LO: 1, 2 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B978032359712800028X#hl00006 Image: Guyton & Hall Textbook of Medical Physiology (12e) - Hall General Mechanisms 2 Na+/K+ ATPase provides concentration gradient for reabsorption of many substances along the nephron Water passively reabsorbed and linked closely to sodium reabsorption and permeability of the different parts of the nephron LO: 1, 2 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B978032359712800028X#hl00007 Image: Guyton & Hall Textbook of Medical Physiology (12e) - Hall Tubular Processing Overview Majority of reabsorption occurs in proximal convoluted tubule Fine tuning of water and solute excretion occurs in more distal parts of nephron under hormonal control Each part of the nephron has distinct functional characteristic caused by differing permeabilities to water/solutes and different membrane transporters 180 litres of filtrate yields about 1.5 litres of urine every day LO: 1, 2 Image: Kumar & Clark’s Clinical Medicine (8e) – Kumar  Proximal Convoluted Tubule Majority of sodium and water reabsorption (~65%) occurs in proximal convoluted tubule (PCT) Brush border increases surface area Mitochondria provide energy Site of secretion of metabolic acids, bases, drugs etc. Tubule fluid leaving PCT is isosmotic as epithelium is freely permeable to water Main site of glucose and LO: 1, 2, 3 amino acid reabsorption Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B978032359712800028X#hl00008 Image: Guyton & Hall Textbook of Medical Physiology (12e) - Hall Glucose and Amino Acids Essentially all glucose and amino acids reabsorbed in PCT Secondary active transport (co-transporters) linked to sodium reabsorption Sodium glucose co- transporters (SGLT2 mainly) on luminal side move glucose against concentration gradient Glucose transporters (GLUT) on basal side allow facilitated diffusion into interstitial fluid Similar process for amino acids LO: 1, 2, 3 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B978032359712800028X#hl00007 Image: Guyton & Hall Textbook of Medical Physiology (12e) - Hall  Glucose and Tm There are a finite number of SGLT transporters on proximal tubule cells Work fine within normal physiological limits of plasma glucose If amount of glucose in filtrate increases, eventually reach a transport maximum (Tm) where reabsorption cannot go any faster This leads to loss of glucose in urine Water LO: 1, 2, is 3 also retained in the tubule lumen and excreted along Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B978032359712800028X#hl00007 with the glucose – ‘osmotic Image: Guyton & Hall Textbook of Medical Physiology (12e) - Hall Secretion of H+ Sodium reabsorption also linked to the secondary active transport of hydrogen ions into lumen (secretion) Important for bicarbonate reabsorption in proximal tubule (see Block 2 acid- base lecture) Na+/H+ exchanger, NHE (antiporter) LO: 1, 2 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B978032359712800028X#hl00007 Image: Guyton & Hall Textbook of Medical Physiology (12e) - Hall  Take a break! Part of the process by Morcheeba https://www.youtube.com/watch?v=Tx6g0h VxCWU  Loop of Henle – Descending Limb Loop of Henle divided into three main parts with slightly different functional characteristics: Thin descending limb Thin ascending limb Thick ascending limb Thin descending limb – permeable to water No active reabsorption or secretion of solutes LO: 1, 2 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B978032359712800028X#hl00009 Image: Guyton & Hall Textbook of Medical Physiology (12e) - Hall  Loop of Henle – Ascending Limb Thin ascending limb – impermeable to water Essentially no active reabsorption or secretion of solutes Thick ascending limb – impermeable to water Active reabsorption of sodium (~25% filtered load) and other solutes ‘Dilutes’ the luminal fluid (hypo- osmotic) as solutes are removed/reabsorbed but water LO: 1, 2 cannot follow Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B978032359712800028X#hl00009 Image: Guyton & Hall Textbook of Medical Physiology (12e) - Hall Thick Ascending Limb Reabsorption from tubule lumen of Sodium Potassium Chloride mediated primarily by sodium, potassium 2- chloride co-transporter (Na+K+2Cl-) Positive charge in lumen encourages paracellular reabsorption of cations (including Ca2+ and Mg2+) As water cannot follow the solutes, the remaining LO: 1, 2 tubular lumen fluid is diluted Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B978032359712800028X#hl00009 Image: Guyton & Hall Textbook of Medical Physiology (12e) - Hall Early Distal Tubule 1 First portion contains the macula densa (sensitive to [NaCl]) – part of the juxtaglomerular apparatus involved with feedback control of GFR and blood pressure Early distal tubule impermeable to water and contributes to dilution of the filtrate Active reabsorption of sodium (~5% filtered load) LO: 1, 2 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B978032359712800028X#hl00009 Images: Medical Sciences (2e) – Naish 75 Guyton & Hall Textbook of Medical Physiology (12e) - Hall Early Distal Tubule 2 Sodium-chloride co- transporter on luminal side Further dilutes the tubular lumen fluid LO: 1, 2 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B978032359712800028X#hl00009 Image: Guyton & Hall Textbook of Medical Physiology (12e) - Hall 75  Late Distal Tubule and Cortical Collecting Both parts have similar functional Tubule characteristics Water permeability of this part of nephron under hormonal control by antidiuretic hormone (ADH): Water permeable when ADH present Water impermeable when ADH absent Two main cell types: Principal cells involved in sodium reabsorption and potassium secretion Intercalated cells involved in LO: 1, 2 potassium Clinicalkey: reabsorption and hydrogen ion secretion (covered in https://www.clinicalkey.com/student/content/book/3-s2.0-B978032359712800028X#hl00009 Image: Guyton & Hall Textbook of Medical Physiology (12e) - Hall 75 Principal cells Sodium enters principal cells through epithelial sodium channels (ENaC) on luminal side Transported out of cells by Na+/K+ ATPase to help maintain concentration gradient Number of ENaC channels and activity of ATPase under hormonal control by aldosterone Therefore an important site of regulation and fine tuning of LO: 1, 2 sodium reabsorption and Clinicalkey: potassium secretion https://www.clinicalkey.com/student/content/book/3-s2.0-B978032359712800028X#hl00009 Image: Guyton & Hall Textbook of Medical Physiology (12e) - Hall 84 Medullary Collecting Duct Final site for urine processing Water permeability of this part of nephron under hormonal control by antidiuretic hormone (ADH) Surrounded by a medullary interstitium with a high concentration of solutes Key role in regulating degree of urine concentration Urea permeability allows medullary interstitium to remain LO: 1, 2 concentrated Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B978032359712800028X#hl00010 Image: Guyton & Hall Textbook of Medical Physiology (12e) - Hall Regulation of Tubular Processes Regulated by local feedback, hormonal and neural mechanisms In contrast to regulation of GFR, reabsorption of individual solutes can be adjusted independently, particularly by hormones acting on different parts of nephron LO: 1, 2 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B978032359712800028X#hl00011 Test your knowledge 1 1. Where in the nephron is fractional glucose reabsorption the highest? 2. What part of the loop of Henle is permeable to water? 3. How does most sodium leave the lumen of the proximal convoluted tubule? a) Na/K-ATPase b) Diffusion c) Facilitated diffusion couple with other solutes d) Through tight junctions e) Passes into loop of Henle Test your knowledge 2 4. The potassium in the renal tubule is: a) Filtered, reabsorbed and secreted b) Filtered and secreted c) Filtered and reabsorbed d) Only filtered e) Only secreted 5. Which hormone controls the extent of water reabsorption in the medullary collecting ducts? Test your knowledge 3 Self-Assessment 1. Compare passive and active transport in relation to the reabsorption and secretion of substances within the renal tubule. 2. Describe the mechanisms and pathways of Na + , glucose, amino acid, Cl – , and water reabsorption by the proximal tubule. Further Reading Physiology 6th edition (Costanzo) Guyton & Hall Textbook of Medical Physiology Medical Sciences (Naish) Acknowledgements Dr Rosemary Bland Dr Jamie Roebuck Answers 1 1. Where in the nephron is fractional glucose reabsorption the highest? Almost all the glucose filtered at the glomerulus is reabsorbed by the proximal convoluted tubule. Approximately 90% of the filtered glucose is reabsorbed by SGLT2 in the early part of the proximal tubule, and the residual 10% is transported by SGLT1 in the latter segments of the proximal tubule 2. What part of the loop of Henle is permeable to water? The thin descending limb is highly permeable to water and moderately permeable to most solutes, including urea and sodium. The function of this nephron segment is mainly to allow simple diffusion of substances through its walls. About 20% of the filtered water is reabsorbed in the loop of Henle, and almost all of this occurs in the thin descending limb. The ascending limb, including both the thin and thick portions, is virtually impermeable to water, a characteristic that is important for concentrating the urine. 3. How does most of the sodium leave the lumen of the proximal convoluted tubule? Answer: c) Facilitated diffusion coupled with other solutes. Most of the Answers 2 4. The potassium in the renal tubule is: Answer a) Filtered, reabsorbed and secreted. The potassium is freely filtered at the glomerulus and is then reabsorbed mainly by the proximal convoluted tubule, but also by the thick ascending limb of the loop of Henle. It is secreted under hormonal control by distal tubule (and cortical collecting duct) principal cells. 5. Which hormone controls the extent of water reabsorption in the medullary collecting ducts? Anti-diuretic hormone (ADH). The most important action of ADH in the kidney is to increase the water permeability of the distal tubule, collecting tubule, and collecting duct epithelia. This helps the body conserve water in circumstances such as dehydration. In the absence of ADH, the permeability of the distal tubules and collecting ducts to water is low, causing the kidneys to excrete large amounts of dilute urine. Thus, the actions of ADH play a key role in controlling the degree of dilution or concentration of the urine.