Urinary Physiology Lecture 1 - Overview of Renal Physiology PDF

Animal Health and the Veterinary Profession VETS10022 Urinary Physiology 1: Overview of Renal Physiology Professor Frankie MacMillan [email protected] Intended learning Outcomes Describe how fluid is distributed between different body fluid compartments and the concept of water balance...

Animal Health and the Veterinary Profession VETS10022 Urinary Physiology 1: Overview of Renal Physiology Professor Frankie MacMillan [email protected] Intended learning Outcomes Describe how fluid is distributed between different body fluid compartments and the concept of water balance State the main functions of the kidney Describe the key features of the nephron as the functional unit of the kidney. Explain the process of glomerular filtration including the structure of the filtration barrier Describe the autoregulation of renal blood flow Signposting to Other teaching Other lectures: Homeostasis, Solute transport, Osmosis Practicals: Osmosis CBL: Fading older cat The thirsty dog The blocked goat Review of Body Fluid distribution SOLID (40%) Cerebrospinal fluid Ocular fluid Fluid in GI tract Joint fluid lymph Transcellular EXTRACELLULAR TOTAL BODY MASS (100%) 1/3 Plasma (20% TBM) WATER (60%) Regulated by kidney INTRACELLULAR 2/3 (40% TBM) Summary of Renal Function Regulation of water balance Water intake vs. water output Regulation of salt balance performed by the kidney alone in most mammals Conservation and regulation of essential substances. e.g. glucose AAs, Ca2+, … Removal of metabolic waste products Urea / uric acid / creatinine / ammonia Removal of foreign substances Drugs or metabolites Regulation of pH - i.e. (H+, HCO3-) The kidney is an important regulatory and excretory organ Overview of balance Overview ofWater Water balance Water in = water out Dry vs. humid environment Dry food or wet food Physiological factors Effects of different extracellular solutions Water movement by osmosis Isotonic  No net movement of water  No change in cell volume  Effective osmotic pressure is the same in ECF & ICF  Normal saline (0.9% NaCl) H2O Hypotonic  Net inward movement of water  Cell volume increases, may lead to lysis  Effective osmotic pressure (tonicity) is lower in ECF than ICF  Pure water Hypertonic  Net outward movement of water  Cell volume reduces crenation  Effective osmotic pressure (tonicity) is greater in ECF than ICF  Sea water or fluid in renal medulla H2O H2O H2O H2O H2O Vital for regulation of water balance is an animal’s ability to produce urine with an osmolarity that is different to that of plasma: Maximum urine concentration in mOsmol/litre: Human Dog Sheep 1500 2300 3200 Kangaroo rat 5500 >10X plasma concentration The Kidney as an organ of excretion and body fluid regulation Common to all vertebrates All can produce hypotonic or isotonic urine Birds and mammals – hypertonic urine Distinguishing feature is Loop of Henle Kidney location and gross anatomy Left kidney Kidneys receive approx. 20% of cardiac output Kidney structure Pyramid Kidney Structure Juxtamedullary nephrons long proximal tubule long loop of Henle 20 % of nephrons Cortical or sub-capsular nephrons short proximal tubule short loop of Henle 80% of nephrons Parts of a nephron Bowman’s capsule Juxta-glomerular apparatus Proximal convoluted tubule Distal tubule Loop of Henlé Descending limb Ascending limb Bowman’s capsule: Glomerulus: arterial blood in a capillary network within a Bowman’s capsule. Filtration occurs here The proximal tubule Most of the filtrate is reabsorbed, along with electrolytes and small molecules The loop of Henlé/ collecting duct Control of urine concentration (in medullary nephrons) The distal tubule Fine tuning of electrolyte concentrations Juxta-glomerular apparatus Production of hormone renin (later lecture) Parts of a nephron Bowman’s capsule Juxta-glomerular apparatus Proximal convoluted tubule Distal tubule Glomerular filtration Loop of Henlé First stage of urine formation Occurs in the glomerulus Results in ultra filtrate in nephron Glomerulus Micropuncture studies show ultra filtrate contains: Ions and small molecules (e.g. glucose) in the same concentration as plasma But does NOT contain cells and only trace amounts of protein Glomerular filtration 1. Fluid filtered from capillary to Bowman’s capsule crosses 3 layers; 2. Endothelial cell of capillary 3. Glomerular basement membrane 4. Visceral epithelial cell (podocyte) of Bowman’s capsule capillary 1. Capillary endothelial cells Flattened cells with thin cytoplasm Fenestrations increase permeability lined with negatively charged glycoprotein. Prevent red blood cells and platelets leaving capillaries capillary 2. Basement Membrane Non cellular, continuous layer of collagen and glycoproteins. capillary Main function - barrier to filtration of large molecules. 3. Podocytes Structure: cell body, trabeculae & pedicels. Main functions: Maintenance of basement membrane. Slit pores between pedicels – lined with negatively charged molecules that repel negatively charged molecules Scanning E.M. of podocytes Composition of ultrafiltrate: Small molecules & ions in almost exactly same concentration as plasma No proteins (e.g. albumen) No blood cells Greater restrictions on filtration for negatively charged molecules Glomerular filtration rate (GFR) How much fluid is filtered per day? In a 20 kg dog: Plasma vol. = 1.6 litres GFR = 80 litres / day Urine output = 0.5 litres 99% reabsorbed In 70kg person GFR ~180 litres per day Why is GFR important clinically? Glomerular filtration rate is vital for normal kidney function. GFR can be impaired in many conditions e.g. infections, parasites, congenital conditions…… Cat Polycystic Kidney Nephritis Dog Kidney What are the forces that determine GFR? Glomerular Filtration Starling’s Forces: Oncotic () and Hydrostatic (P) pressures Net filtration pressure(NFP) = forces out - forces in: = (Pcap + bc) – (Pbc + cap) bc = 0  NFP = Pcap – (cap+ Pbc) Other Factors Affecting GFR Blood pressure Low BP – renal failure No filtration Long term high BP – Damage to filtration barrier Hydrostatic pressure in bowman's capsule Kidney stones -blockage in ureter  filtration Plasma protein levels Low protein oncotic pressure filtration Protein levels in bowman's capsule Nephrotic syndrome -Failure of filtration Barrier  oncotic pressure filtration Regulation of GFR: Afferent and efferent arterioles Constriction of afferent arteriole Glomerular capillary efferent arteriole ↓ Hydrostatic pressure ↓ Blood flow Reduced filtration Constriction of efferent arteriole afferent arteriole ↑ Hydrostatic pressure ↓ Blood flow Little change in filtration Autoregulation of Renal Blood Flow Occurs within arterial blood pressure range 80-180mmHg Renal blood flow and GFR is very constant Autoregulation of Renal Blood Flow Does not depend on nerve supply: therefore, is due to intrinsic factors in kidney Two mechanisms: 1. Myogenic – smooth muscle in afferent and efferent arterioles 2. Tubulo-glomerular feedback –feedback from distal tubule fluid to juxtaglomerular apparatus Juxtaglomerular apparatus Extrinsic Control of Renal blood flow Sympathetic vasoconstrictor activity on afferent arteriole Other factors Vasoconstriction in kidneys is attenuated by local release of vasodilators e.g. prostaglandins, nitric oxide (NO). Severe reduction in Arterial blood pressure will depress renal blood flow and may lead to acute renal failure Key points  The kidneys have several vital homeostatic functions ranging from regulation of the composition and volume of plasma, retrieval of useful metabolites, elimination of waste materials and production or activation of hormones and other regulatory molecules.  The individual functioning unit of the kidneys is the nephron and different regions are specialised to carry out the numerous and vital functions of the kidneys.  The first stage of urine formation is glomerular filtration that occurs in the glomerulus.  Starling’s forces dictate the rate of filtration  Factors act to maintain the rate of ultrafiltrate formation.  Intrinsic mechanisms regulate renal blood flow