Renal Physiology 2011 Lisa M. Harrison-Bernard, PhD lharris@lsuhsc.edu Renal Physiology - Lectures Physiology of Body Fluids 2. Structure & Function of the Kidneys 3. Renal Clearance & Glomerular Filtration 4. Regulation of Renal Blood Flow 5. Transport of Sodium & Chloride 6. Transport of Urea, Glucose, Phosphate, Calcium & Organic Solutes 7. Regulation of Potassium Balance 8. Regulation of Water Balance 9. Transport of Acids & Bases 10. Integration of Salt & Water Balance 11. Clinical Correlation Dr. Credo 12. PROBLEM SET REVIEW May 9, 2011 13. EXAM REVIEW May 9, 2011 14. EXAM IV May 12, 2011 LSU Medical Physiology 2010 1
How Many Students Have Studied the Kidney: Anatomy? Histology? Physiology? How to Approach Renal Physiology? Gross Anatomy + Histology + Clinical Medicine + CV Physiology Respiratory + Endocrine Physiology + + GI Physiology Physiology LSU Medical Physiology 2010 2
APPENDIX A. Integrative Case Studies B. Normal Laboratory Values C. Nephron Function Transport Processes Nephron Segment D. Answers to Self Study Problems WHY Does a Medical Student Need to Learn Renal Physiology? 23 million adult patients kidney disease 90,000 deaths/yr 530,000 ESRD/yr 370,000 hemodialysis/peritoneal dialysis 18,000 kidney transplants/yr & 86,000 waiting ESRD $35 billion/yr 9 th leading cause of death LSU Medical Physiology 2010 3
WHAT Does a Nephrologist Expect a Medical Student to Know? 1) What is GFR? How is it determined? How is it estimated? 2) Body Fluid Compartments 3) Regulation of Sodium & Water Balance 4) Potassium Homeostasis 5) Acid/Base Physiology Renal Physiology Lecture 2 Structure and Function of the Kidneys Reading Assignment: Chapter 2 Koeppen & Stanton Renal Physiology 1. Function 2. Review Anatomy 3. Juxtaglomerular Apparatus 4. Filtration Barrier 5. Basic Renal Processes LSU Medical Physiology 2010 4
Which is most important in regulating water balance? a) Water lost through skin and lungs b) Water lost in feces c) Water lost in sweat d) Urine production Correct answer d) What are the functions of the kidney??? LSU Medical Physiology 2010 5
Functions of Kidney Major regulation of body water & inorganic ions = ECF Regulate body fluid osmolality volume Functions of Kidney Regulate water & inorganicion balance BP H 2 O, Na +, K +, Ca 2+, Cl -, Mg 2+, etc. Acid-base balance Eliminate metabolic waste products Urea, uric acid, creatinine LSU Medical Physiology 2010 6
Functions of Kidney Eliminate foreign compounds Drugs, toxins, pesticides Gluconeogenesis Secrete hormones Erythropoietin Renin 1,25-dihydroxy Vitamin D3 ** Renal Failure Patient ** Patient Data Plasma K+ P Urea BP P PO4- Hematocrit P HCO3- P ph P Ca2+ Normal LSU Medical Physiology 2010 7
Renal Physiology Lecture 2 Function 2. REVIEW ANATOMY 3. Juxtaglomerular Apparatus 4. Filtration Barrier 5. Basic Renal Processes Basic Anatomical Structure of Kidneys Retroperitoneal 12 th thoracic- 3 rd lumbar vertebrae LSU Medical Physiology 2010 8
Section of Human Kidney ~ Fig 2-1 Functional unit of kidney 800,000 1,200,000 nephrons/ kidney Arterial Vessels & Capillaries Venous Vessels Tubules Peritubular Capillaries Medullary Capillary Plexus Kriz, 1991 LSU Medical Physiology 2010 9
Structure of Nephron ~ Fig 2-2 DCT JMN AA Bowman s PCT PST TAL Cortex Medulla tdlh talh Important Characteristics of Renal Vasculature ~ Fig 2-2 Virtually ALL blood entering kidney flows through glomeruli - ALL located in cortex! 2 capillary beds in sequence: Glomerular capillaries Postglomerular capillaries LSU Medical Physiology 2010 10
Important Characteristics of Renal Vasculature ~ Fig 2-2 2 types postglomerular capillaries: Cortex - Peritubular capillaries i Medulla - Vasa recta Inflow & outflow vessels of glomerular capillaries are arterioles: Inflow - Afferent arteriole Outflow - Efferent arteriole (exit) Scanning EM - Renal Vasculature ~ Fig 2-6 Afferent Arteriole Glomerulus Artery Courtesy of Kate Denton Ph.D., Monash University LSU Medical Physiology 2010 11
Scanning EM Glomerulus Between Afferent and Efferent Arterioles ~ Fig 2-6 PC Peritubular Capillary EA Efferent Arteriole Glomerular Capillary AA Afferent Arteriole Scanning EM Podocytes ~ Fig 2-8 Podocyte cells with feet LSU Medical Physiology 2010 12
Distribution of Blood Flow CO = 5 L/min 20% of CO RBF = 1 L/min Cortex 90% Medulla 10% Renal Physiology Lecture 2 Function Review Anatomy 3. JUXTAGLOMERULAR APPARATUS 4. Filtration Barrier 5. Basic Renal Processes LSU Medical Physiology 2010 13
Juxtaglomerular Apparatus ~ Fig 2-5 1. 3. 2. 1. Juxtaglomerular Cells of afferent arteriole 2. Macula Densa Cells of thick ascending limb of loop of Henle (TAL, spot dark) 3. Extraglomerular Mesangial Cells Juxtaglomerular Apparatus Communication between TAL of loop & afferent arteriole of same nephron Afferent arteriole Macula densa cells,tal LSU Medical Physiology 2010 14
Renal Physiology Lecture 2 Function Review Anatomy Juxtaglomerular Apparatus 4. FILTRATION BARRIER 5. Basic Renal Processes Filtration Barrier LSU Medical Physiology 2010 15
Filtration Barrier ~ Fig 2-7 RBC Capillary Lumen Urinary Space } 1. Capillary Endothelium with Fenestrations 2. Glomerular Basement Membrane 3. Podocyte with Filtration Slit Diaphragm Filtration Barrier Fig 2-7,8 1. Endothelium fenestrations (windows) 70 nm holes limit filtration of cellular elements RBC WBC, platelets 2. Basement Membrane prefilter Barrier to protein Charge selective filter LSU Medical Physiology 2010 16
Filtration Barrier ~ Fig 2-8 3. Podocyte with Filtration Slit Diaphragm size selective filter 4-14 nm pores, negative charged glycoproteins NEGATIVELY charged glycoproteins on surfaces ALL components of glomerular filtration barrier Filtration Slit Diaphragm ~ Fig 2-9 Podocin Nephrin NEPH-1 Podocyte Podocyte GBM Mutations in Nephrin, NEPH-1, Podocin = Proteinuria = Nephrotic Syndrome Endo LSU Medical Physiology 2010 17
What would happen if negative charges were obliterated? Causes of Glomerular Disease Albumin primary plasma protein NORMALLY too large filtered (69 kda) charged Alter size and/or chargeselective properties of filtration barrier = Proteinuria protein in urine - earliest sign and hallmark of renal disease LSU Medical Physiology 2010 18
Clinical Examples of Glomerular Pathology Endothelium swell Basement membrane thickens diabetes Podocyctes foot processes fuse reduce filtration increased pore size - proteinuria Clinical Examples of Glomerular Disease Loss of negative charge on membranes secondary to immunological damage and inflammation filter albumin proteinuria LSU Medical Physiology 2010 19
Glomerular Filtrate Water only enters nephron by filtration 1 st step in urine formation Electrolytes freely filtered Glom conc = Plasma conc Macromolecules not filtered <10,000 MW filtered Glomerular Filtrate Net glomerular filtration pressure initiates urine formation: forcing cell-free, essentially protein-free filtrate of plasma driven by Starling s forces out of glomeruli into Bowman s space down tubule into renal pelvis LSU Medical Physiology 2010 20
Renal Physiology Lecture 2 Function Review Anatomy Juxtaglomerular Apparatus Filtration Barrier 5. BASIC RENAL PROCESSES Luminal section of plasma membrane of tubule cells faces filtrate Basolateral section in close proximity to peritubular capillary (blood side) LSU Medical Physiology 2010 21
1. Filtration Renal Processes Glomerular capillary lumen Bowman s space (bulk flow) 2. Tubular Reabsorption Tubular lumen peritubular capillary plasma 3. Tubular Secretion Peritubular plasma (capillary lumen) interstitial space tubular cell tubular lumen (tubular cell interior to tubular lumen) Basic Renal Processes Amount Excreted in Urine = Amount Filtered + Amount Secreted Amount Reabsorbed LSU Medical Physiology 2010 22
Glomerular Filtration Net filtration of fluid across all capillaries (except kidney) = 4 L/d Glomerular Filtration Rate - GFR = 125 ml/min (both kidneys) = 180 L/day Plasma volume - PV = 3 L = filtered 60X /d ECFV = 17 L = filtered 10X /d Tubular Reabsorption Small % filtered amounts excreted tubules reabsorb into body HUGE amounts fluid & solutes > 99% volume filtered (GFR) reabsorbed LSU Medical Physiology 2010 23
Tubular Reabsorption Filtered Load > Excretion Rate Net reabsorption of substance Filtered Load NaCl = 3-4 # / d Glucose = 1/2 # / d REABSORPTION IS IMPERATIVE!! Filtration and Reabsorption Amount Filter/d Amount Excrete/d % Reabsorb Water (L) 180 1.8 99.0 K + (meq) 720 100 86.1 Ca 2+ (meq) 540 10 98.2 HCO 3 - (meq) 4,320 2 99.9+ Cl - (meq) 18,000 150 99.2 Na + (g) 630 3.2 99.5 Glucose (g) 180 0 100 Urea (g) 54 30 44 LSU Medical Physiology 2010 24
Tubular Secretion Most important: H + K + Organic anions choline creatinine Foreign chemicals penicillin Summary 1. Kidney is a very important organ. 2. Juxtaglomerular apparatus is coolest. 3. 3 basic renal processes Filtration, reabsorption, secretion 4. Damage to filtration barrier results in glomerular disease LSU Medical Physiology 2010 25
THE END LSU Medical Physiology 2010 26