Renal Physiology - Distal Convoluted Tubule PDF

Last edited: 3/25/2022 DISTAL CONVOLUTED TUBULE Distal Convoluted Tubule Medical Editor: Mariel Antoinette L. Perez OUTLINE I) RECAP II) DISTAL CONVOLUTED TUBULE...

Last edited: 3/25/2022 DISTAL CONVOLUTED TUBULE Distal Convoluted Tubule Medical Editor: Mariel Antoinette L. Perez OUTLINE I) RECAP II) DISTAL CONVOLUTED TUBULE III) APPENDIX (A) PROXIMAL CONVOLUTED TUBULE PCT (A) EARLY DISTAL TUBULE IV) REVIEW QUESTIONS (B) LOOP OF HENLE (B) LATE DISTAL TUBULE V) REFRENCES I) RECAP (A) PROXIMAL CONVOLUTED TUBULE (PCT) Tubular Reabsorption Tubular Secretion (B) LOOP OF HENLE Descending Limb Ascending Limb o Na+/K+/2Cl– transporters  Pushes these solutes out into the medullary interstitium (Salty; high osmolality)  Some K+ gets pushed back in the lumen, creating a depolarization on the inner side of the membrane of the ascending limb Causes Mg2+ and Ca2+ to undergo paracellular transport Salty medullary interstitium  water is pulled out Importance: o In the PCT  65% of water was reabsorbed  65% of sodium was reabsorbed  300 mosm o In the descending limb,  15% of water was absorbed  300 mosm  500  700  900  1200 o Going into Distal Convoluted Tubule (DCT),  There’s only ~20% water left  There’s only ~10% sodium left (25% of sodium was reabsorbed in the thick ascending limb of the loop of Henle)  100-200 mosm Counter-Current Multiplier Mechanism o Maintained by the vasa recta  Counter-current exchanger DISTAL CONVOLUTED TUBULE RENAL PHYSIOLOGY: Note #4. 1 of 4  II) DISTAL CONVOLUTED TUBULE (A) EARLY DISTAL TUBULE (1) Sodium-Potassium Pump (3) Calcium Specialized channels in basolateral membrane Low blood calcium levels stimulate parathyroid gland to Requires presence of ATP secrete PTH Pumps 3 Na+ ions out and 2 K+ ions in o PTH: parathyroid hormone (2) Sodium-Chloride Symporter PTH has a receptor on the cell of the distal convoluted tubule o PTH binds and stimulates the receptor Specialized transporters on the lumina membrane closest o Receptor activates a second messenger system to the urine o Activates G stimulatory protein which binds GTP Sodium and Chloride both go into the cell o GTP binds to cofactor enzyme, adenylate cyclase o Since Na+ ions are going out via the Na-K pump, it  Converts ATP  cAMP means that DCT has [Na+] o cAMP activates protein kinase A  it’s going along its concentration gradient  Only 5-6% of Na+ is being reabsorbed here Protein Kinase A stimulates calcium modulated 4-5% is left channels via phosphorylation o Cl– has a special channel that pumps it into the blood o Causes channels to pull in Ca2+ into the cell  Calcium may be bound to protein called calbindin (i) Thiazide o Channels are very sensitive to levels of PTH o Diuretic that inhibits sodium-chloride symporter Even if blood calcium level is low, there’s still less calcium o It will affect both the salt and water reabsorption inside the cell  Instead of reabsorbing the 5-6% back, you’ll lose o Hence, calcium will be moving against its them to the urine concentration gradient from the cell into the blood  Lose a bit of the blood volume o Two mechanisms to get calcium out This is called Diuresis  Ca2+/Na+ Transporter Proteins on the basolateral membrane Pumps calcium out and brings sodium in Secondary active transport  Ca2+/H+ Transporter Uses ATP 2 of 4 RENAL PHYSIOLOGY: Note #4 DISTAL CONVOLUTED TUBULE  (B) LATE DISTAL TUBULE Generally impermeable to water Has specialized cells responsible for responding to aldosterone (1) Aldosterone (2) Antidiuretic hormone/ Steroid hormone produced in the top part (globular cells) of the adrenal gland Vasopressin o Adrenal gland is located on top of the kidneys Can act on these cells as well Stimulus Presence of ADH will open up the o Angiotensin-II aquaporins  Angiotensin wants to increase pressure o Water will have to follow the o Hyponatremia salt and go into the cell  When [Na+] levels in the blood is decreasing o H2O volume getting pulled o Hyperkalemia into the bloodstream   When [K+] levels in the blood is increasing increases blood pressure Aldosterone passes through the cell’s lipid bilayer o Because it’s a steroid hormone Once inside the cell, it will activate specific transcription factors to produces proteins (i) Sodium channel  Protein embedded in the luminal membrane  Sodium is allowed to go inside the cell due to the effects of the Na+/K+ Transporter (ii) Na+/K+ Transporter  Protein found in the basolateral membrane  Active transport: uses ATP  Transports 3 [Na+] out and 2 [K+] into the cell Na+ leaves the cell  [Na+] in the cell o Na+ would want to go from high concentration to low concentration  Na+ goes inside the cell via the sodium channel [K ] enters the cell  [K+] in the cell + (iii) Potassium channel  embedded in the luminal membrane  Since there’s [K+] inside the cell, the channel will move it out of the cell where it will eventually be excreted into the urine DISTAL CONVOLUTED TUBULE RENAL PHYSIOLOGY: Note #4. 3 of 4  III) APPENDIX Figure 1. Summary of Distal Convoluted Tubule Lecture IV) REVIEW QUESTIONS V) REFRENCES 1) Which of the following hormones synthesized in the Sabatine MS. Pocket Medicine: the Massachusetts General Hospital Handbook of Internal Medicine. Philadelphia: Wolters adrenal gland activate specific transcription factors? Kluwer; 2020. a) aldosterone Le T. First Aid for the USMLE Step 1 2020. 30th anniversary b) Antidiuretic hormone edition: McGraw Hill; 2020. Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL, c) Vasopressin Loscalzo J. Harrison's Principles of Internal Medicine, Twentieth d) Calmodulin Edition (Vol.1 & Vol.2). McGraw-Hill Education / Medical; 2018 Marieb EN, Hoehn K. Anatomy & Physiology. Hoboken, NJ: 2) What does increased blood volume (water Pearson; 2020. reabsorption) do to the blood pressure? Boron WF, Boulpaep EL. Medical Physiology.; 2017. a) Increases blood pressure Guyton and Hall Textbook of Medical Physiology. Philadelphia, PA: Elsevier; 2021. c) Not related d) Depends on other factors 3) What triggers aldosterone production? a) hypernatremia b) hypokalemia c) angiotensin-I d) hyperkalemia 4 of 4 RENAL PHYSIOLOGY: Note #4 DISTAL CONVOLUTED TUBULE