Renal Physiology Lecture Notes (Paramedicine I F2024) PDF

PAR3623 Paramedicine – Medical Physiology I F2024 Lecture 16 Renal overview continued and filtration  Copyright / Intellectual Property Notice Materials posted to courses are subject to Intellectual Property and Copyright protection, and as such cannot be us...

PAR3623 Paramedicine – Medical Physiology I F2024 Lecture 16 Renal overview continued and filtration  Copyright / Intellectual Property Notice Materials posted to courses are subject to Intellectual Property and Copyright protection, and as such cannot be used and posted for public dissemination without prior permission from the College. For clarity, these protections are automatic once a work is created, and applies whether or not a copyright statement appears on the material. Students are bound by College policies, including AA 34 - Copyright, and SA 07 - Student Code of Conduct, and any student found to be using or posting course materials for public dissemination without permission is in breach of these policies and may be sanctioned. Dr. Pasan Fernando  Need HELP?? If you need help: 1. Email me for an appointment – can meet individually or as a group 2. Chat with me after or before class Email responses follow the AC policy – 48h grace (not including weekends and holidays) Expect email responses from me during regular College business hours with some exceptions. Ø After the 48h, please send me a polite reminder. J Dr. Pasan Fernando 4  Dr. Pasan Fernando 5  Smooth muscle contraction can be initiated in a few ways: § Mechanically gated Ca2+ channels opening due to stretch § NT binding to Ca2+ ligand gated channel § NT or hormone binding to GPCR Ø GPCR binding initiates an intracellular cascade Ø GPCR activation offers the most complex and diverse control over cellular functions Dr. Pasan Fernando 6  GPCR activation § G proteins have the ability to bind to nucleotides GTP and GDP § 7 membrane spanning domain § Intracellular tripeptide unit (alpha, beta, gamma) § G protein alpha is inactive when bound to GDP, active when bound to GTP § When ligand binds GPCR, GDP is exchanged for GTP § G protein separates into GTP alpha and beta/gamma dimmer § In most cases, both remain attached to the plasma membrane; move along membrane to Dr. Pasan Fernando activate other targets § When GTP is hydrolyzed to GDP or when ligand dissociates, GPCR complex goes back to inactive state 7  The cAMP/PKA pathway § Cyclic adenosine monophosphate (cAMP) is a second messenger § 2nd messengers start a cascade of reactions that regulate cellular activity, metabolism, physiological processes § The first messenger is typically a hormone or neurotransmitter. § The first messenger wants to create certain effects but can’t do so directly - requires a second messenger Dr. Pasan Fernando 8  § What’s the advantage of having cellular effects occur through a second messenger system instead of a direct messenger? Dr. Pasan Fernando 9  Kidney – Microscopic features Two types of nephrons § Microscopic functional units of the kidney § Approx. 1 million/kidney 1.Cortical nephrons – 85 percent of all nephrons – Located primarily in the cortex – Responsible for most regulatory functions 2. Juxtamedullary nephrons Ø 15 percent of all nephrons Ø Long nephron loop extending deep into medulla Dr. Pasan Fernando Ø Essential to producing concentrated urine 10  The Nephron – Overview Two components 1. Renal corpuscle Ø Blood pressure forces water and solutes out of the glomerular capillaries in a process called filtration – Produces filtrate (protein-free solution, similar to blood plasma) Ø Collected in the surrounding capsular space 2. Renal tubule Ø Tubular passageway up to 50 mm long Ø Receives filtrate and modifies it to create urine Dr. Pasan Fernando 11  Renal Corpuscle - Glomerulus Two parts of renal corpuscle 1. Glomerulus § Tuft of capillaries composed of fenestrated endothelium Ø Highly porous capillaries Ø Allows for efficient filtrate formation – Filtrate: plasma-derived fluid that renal tubules process to form urine Dr. Pasan Fernando 12  Renal Corpuscle – Glomerular capsule 2. Glomerular capsule § Also called Bowman’s capsule: cup- shaped, hollow structure surrounding glomerulus § Consists of two layers Ø Parietal layer: simple squamous epithelium Ø Visceral layer : clings to glomerular capillaries; branching epithelial podocytes – Extensions terminate in foot processes that cling to basement membrane Dr. Pasan Fernando – Filtration slits between foot processes allow filtrate to pass into capsular space 13  Formation of the Filtration Membrane Dr. Pasan Fernando 14  Nephron – Proximal convoluted tubule Proximal convoluted tubule (PCT) Ø Reabsorbs nutrients from the filtrate (now called tubular fluid) Ø Winding nature increases residence time in tubules Ø Allows optimum time for exchange of tubular fluid components Ø Cuboidal epithelium Dr. Pasan Fernando 15  Nephron – Nephron loop 2. Nephron loop § Formerly called loop of Henle § U-shaped structure consisting of two limbs Ø Descending limb – Proximal part of descending limb is continuous with proximal tubule – Distal portion also called descending thin limb; simple squamous epithelium Ø Ascending limb – Thick ascending limb » Thin in some nephrons Dr. Pasan Fernando – Cuboidal or columnar cells 16  Nephron – Distal convoluted tubule Distal convoluted tubule (DCT) § Cuboidal cells with very few microvilli § Function more in secretion than reabsorption § Confined to cortex Dr. Pasan Fernando 17  Nephron - Segments § Direction of flow for tubular fluid and surrounding interstitial fluid (peritubular fluid) varies at each nephron segment § Water and solutes are reabsorbed in different regions of nephron § Reabsorption can be regulated by hormones in some regions (variable) Dr. Pasan Fernando 18  Nephron – Collecting system Collecting system § Series of tubes carrying tubular fluid away from the nephron § Collecting duct Ø Collects fluid from many nephrons Ø Carries fluid through the renal medulla Ø Lined with two main types of cells: – Intercalated cells (play a role in secreting and reabsorbing hydrogen and bicarbonate ions) – Principal cells (reabsorb water and Na+, secrete K+) Dr. Pasan Fernando 19  Nephron – Collecting system § Papillary duct Ø Collects fluid from multiple collecting ducts Ø Delivers fluid to minor calyx Dr. Pasan Fernando 20  Dr. Pasan Fernando 21  Drugs Will Target Different Segments of the Nephron Dr. Pasan Fernando 22 Dr. Pasan Fernando Nephrons Dr. Pasan Fernando  Renal Blood Supply Dr. Pasan Fernando 25  Nephron Capillary Beds and Blood Flow Dr. Pasan Fernando 26  Nephron Capillary Beds § Renal tubule closely associated with two capillary beds: § Glomerulus – produces filtrate § Peritubular capillaries & vasa recta – reclaims most of the filtrate Dr. Pasan Fernando 27  Nephron Capillary Beds - Glomerular Glomerular capillary bed § Capillaries are specialized for filtration § Different from other capillary beds because they are fed and drained by arteriole Ø Afferent arteriole enters glomerulus and leaves via efferent arteriole – Afferent arteriole arises from cortical radiate arteries – Efferent feed into either peritubular capillaries or vasa recta § Blood pressure in glomerulus high because: Ø Afferent arterioles are larger in diameter than efferent arterioles Dr. Pasan Fernando Ø Arterioles are high-resistance vessels 28  Nephron Capillary Beds – Peritubular Capillaries Peritubular capillaries § Low-pressure, porous capillaries adapted for absorption of water and solutes § Arise from efferent arterioles § Cling to adjacent renal tubules in cortex § Empty into venules Dr. Pasan Fernando 29  Nephron Capillary Beds – Vasa recta Vasa recta § Long, thin-walled vessels parallel to long nephron loops of juxtamedullary nephrons § Arise from efferent arterioles serving juxtamedullary nephrons Ø Instead of peritubular capillaries § Function in formation of concentrated urine Dr. Pasan Fernando 30 Dr. Pasan Fernando  Juxtaglomerular Complex § Each nephron has one juxtaglomerular complex (JGC) § Involves modified portions of: Ø Distal portion of ascending limb of nephron loop Ø Afferent (sometimes efferent) arteriole § Important in regulating rate of filtrate formation and blood pressure Dr. Pasan Fernando 32  Juxtaglomerular Complex - Cells Three cell populations are seen in JGC: 1. Macula densa – Tall, closely packed cells of ascending limb – Contain chemoreceptors that sense NaCl content of filtrate 2. Granular cells (juxtaglomerular cells) – Enlarged, smooth muscle cells of arteriole – Act as mechanoreceptors to sense blood pressure in afferent arteriole – Contain secretory granules that contain enzyme renin 3. Mesangial cells Located between arteriole and tubule cells Dr. Pasan Fernando Interconnected with gap junctions May pass signals between macula densa and granular cells 33  Dr. Pasan Fernando 34  Physiology of Kidney Function – Filtration, absorption, secretion § 180 L of fluid processed daily, but only 1.5 L of urine is formed § Kidneys filter body’s entire plasma volume 60 times each day § Consume 20–25% of oxygen used by body at rest § Filtrate (produced by glomerular filtration) is basically blood plasma minus proteins § Urine is produced from filtrate Ø Urine – 99 percent of glucose, amino acids, and other organic nutrients Ø Sodium, potassium, bicarbonate, magnesium, phosphate, sulfate ions Ø Water (about 108 liters each day) – Solute concentration of tubular fluid decreases – Water moves into the peritubular Dr. Pasan Fernando fluid 42  Urine Formation - Secretion Secretion § Secretion occurs mostly in the DCT § Movement of water and solutes out of peritubular fluid into the tubular fluid § Only 15–20 percent of the initial filtrate volume reaches the distal convoluted tubule (DCT) § Combination of reabsorption and secretion in the DCT alters solute composition in the tubular fluid Ø Sodium ions are reabsorbed in exchange for potassium ions (pumps are stimulated by aldosterone) Ø Hydrogen ions are secreted in exchange for sodium ions (to increase pH of body fluids) Dr. Pasan Fernando Ø Carrier proteins also secrete toxins or drugs 43  Dr. Pasan Fernando 44  Dr. Pasan Fernando 45  Dr. Pasan Fernando 46