Introduction to Renal Transport and its Disorders

1. Introduction to Renal Transport and its Disorders Dr. Linda N. Peterson Linda.peterson@ubc.ca

2. How to get the most out of this part of the course • The objectives- see handout and website- read the notes under slides. Group Assignments. Download and view on your computer • http://www.cellphys.ubc.ca/undergrad_physcourses.htm • Assessment in the Course- See objectives document • Reflective Essay (written) 10% • Examination 90% • Worth 33% of the mid-term • What can I expect from you as learners? • What can you expect from me as a teacher? Linda N Peterson UBC

3. Putting things in perspective

4. From Fish to PhilosopherHomer Smith MD Linda N Peterson UBC

5. How are all of these molecules moved? DCT Linda Peterson@ubc.ca

6. Filtration • Some basic ideas and terms Reabsorption Secretion Excretion Linda N Peterson UBC

7. Transporting epithelial cells are polarized Intrinsic property of these cells to form single layers with cells joined by tight junctions GI tract, Kidney, Eye, Ear, Ventricles of the Brain These cells form one cell layer thick sheets in culture and the renal tubules are one cell layer thick Linda N Peterson UBC

8. Polar Epithelium Pump is along the blood-side of all cells which form the nephron Almost all movement of ions and molecules is somehow linked to the action of the Na-K-ATPase pump

9. TUBULAR NOMENCLATURE (Transport through and between cells Cell Transcellular Paracellular (Transport between cells i.e. TJs)

10. Paracellular Transport • Paracellular – ions, and water may move through the tight junctions. We will see that permeability of the tight junctions to water differs from very high to extremely low and that the tight junctions have ion selectively to some extent. • Is movement through this path active or passive?

11. Transcellular Transport • Ions and other molecules are moving through 2 cell membranes- water is not always allowed to follow

12. Paracellular-between cells Transcellular- through cells Reabsorption Secretion Blood Side

13. Getting through cells • Lipid bilayer- very hydrophobic cell membrane • How do substances, many of which are polar or charged and therefore hydrophyllic, get through cell membranes? • Diffusion, endocytosis, or some molecular alteration of the cell membrane?

14. Receptor Mediated Endocytosis TYPES OF TRANSPORT MECHANISMS • Endocytosis of filtered proteins occur in the proximal convoluted tubule • Albumen is the most abundant • Proteins are catabolized • in the cell and amino acids are transported into Blood • Normal protein lost is max 150 mg per day- most of this is albumen

15. CELL HAS EVERYTHING FOR THE PURPOSE OF DISCUSSION READ THE NOTES Channels _ _ Primary Active _ 20 Active _

16. With the EC gradient-Downhill Single file, extraordinary speed of movement Carrier Mediated Transport Proteins Ions and molecules physically bind to these transport proteins Against EC gradient-Up Hill Breakdown of ATP provides the energy for transport Passive or Linda N Peterson UBC

17. Primary Active TransportNa-K-ATPase Drives virtually all renal transport

18. Structure of the Na-K-ATPase pump

19. With the EC gradient-Downhill Single file, extraordinary speed of movement Carrier Mediated Transport Proteins Ions and molecules physically bind to these transport proteins Against EC gradient-Up Hill Breakdown of ATP provides the energy for transport Passive or Linda N Peterson UBC

20. Facilitated Diffusion is the simpliest form of carrier mediated transport Facilitated Diffusion Facilitated Diffusion is the simplest from of carrier mediated transport Notice all the molecules are the same! Is this active or passive transport?

21. CELL HAS EVERYTHING FOR THE PURPOSE OF DISCUSSION READ THE NOTES Channels _ _ Primary Active _ 20 Active _

22. Co-transporters/Symporters Na- glucose SGLUTs Na- amino acids Na-K-2Cl Na-Cl Na- phosphate Inwardly directed -K-Cl Na-bicarbonate Exchangers/Antiporters Na-Ca Na-H Cl-bicarbonate Cl – formate PAH-alpha ketoglutarate Sulfate-Anion What types of secondary active transporters are there?

23. Carrier mediated transport will be saturable, show stereospecificity for the binding sites- competition kinetics What does that mean? Linda N Peterson UBC

24. With the EC gradient-Downhill Single file, extraordinary speed of movement Ions and molecules physically bind to these transport proteins Against EC gradient-Up Hill Ion Channels Breakdown of ATP provides the energy for transport Passive or Linda N Peterson UBC

25. What can cause changes in transport in a nephron segment?

26. Changes in transport in a nephron segment can be caused by: • Over loading these carrier mediated transport systems • Blocking these transport proteins • Increasing or decreasing the capacity (numbers) and/or function of these transport proteins • Decreased/eliminated or enhanced by mutations in transport proteins • Upstream changes in transport

28. Proximal TransportComing soon! • Segmental differences in transport are due to the expression of different transporters in the cells • Transport in first third of the PT affects transport in the last two-thirds of the PT • Changes in transport in the PT can affect transport in downstream nephron segments

29. Discussion QuestionsSee Group Assignment Sheet You have just been told that you have: • Groups 1: “diabetes mellitus” • Groups 2: “nephrogenic glycosuria” • Groups 3: “diabetes insipidus” What effect does the disorder have on renal glucose excretion? What is the underlying cause? Are there any changes in NaCl, K or water excretion? Will it change your life in a fundamental way?