Lec 52. Overview of Renal Physiology PDF

Introduction into Renal Physiology Lecture 1 Highlights: 1. 2. 3. 4. 5. Kidney functions Kidney anatomy Nephron - functional unit of kidneys Three processes of urine formation and balance equation Renal plasma clearance Objectives: 1. Describe major functions of the kidney including homeostatic...

Introduction into Renal Physiology Lecture 1 Highlights: 1. 2. 3. 4. 5. Kidney functions Kidney anatomy Nephron - functional unit of kidneys Three processes of urine formation and balance equation Renal plasma clearance Objectives: 1. Describe major functions of the kidney including homeostatic regulation and endocrine secretion. 2. Identify the sites of renal hormone production, adequate stimulus for their release, and their effects on target tissues. 3. Describe the microanatomy of the kidney including the renal cortex, medulla, calyces, hilus, medullary pyramids, pelvic space, ureter, renal artery, and vein. 4. Identify each structure of the nephron (such as the renal corpuscle, proximal tubule, limbs of Henle’s loop, distal tubule, collecting tubule etc.) in the renal cortex or renal medulla. 5. Relate each structure to the function it performs (process that takes place in this structure or segment). 6. Based on the location of glomerulus and the length of the loop of Henle, distinguish between the cortical and juxtamedullary nephrons. 7. Explain renal handling of substances and their excretion as a particular combination of filtration, reabsorption and secretion. 8. Explain relationship among filtration, excretion and plasma clearance for various substances, define filtered load. Urinary System. Introduction. Upper A. urinary B. tract Kidneys Ureters - transport urine produced by the kidney to the urinary bladder Lower C. urinary tract D. Urinary bladder – stores urine Urethra – discharges urine from the body Ureter Urinary bladder Urethra Kidney Functions: 1. Excretory – filtering blood, removing wastes (urea, creatinin, etc.) and toxins with urine 2. Regulatory – contributes to homeostasis of the body fluids in several ways 3. Endocrine - release of several hormones a. Calcitriol b. Erythropoetin c. Renin d. Renalase Calcitriol is a steroid, other hormones are proteins Kidney Hormones a. Calcitriol – regulation of blood level of Ca++ and phosphate, active form of vitamin D (1,25 – dihydroxycholecalciferol), increases intestinal absorption of Ca++ and HPO4-2 b. Erythropoetin - regulation of red blood cell production, glycoprotein, promotes maturation of bone marrow stem cells into erythrocytes; stimulus for release: low partial pressure of O2; Chronic renal disease causes erythropoetin insufficiency = normocytic normochromic anemia (normal size and amount of pigment hemoglobin) Anemia? Kidney Hormones: c. Renin – regulation of Na+ balance, blood pressure and K+ balance d. Renalase - breakdown of blood catecholamines (e.g. adrenaline) Regulatory Function of the Kidney: maintenance (homeostasis) of: a. blood electrolyte (ionic) composition including – Na+, K+, Ca++, Cl-, HPO4-2 b. blood osmolarity close to 290 mOsm/L, depends on regulation of body water by the kidney c. blood volume and blood pressure mainly by regulating body’s Na+ content in extracellular fluid d. blood pH via excretion of H+ and conservation of bicarbonate ion HCO3e. blood glucose External Anatomy of the Kidneys Adrenal Gland Renal hilus or hilum Renal Artery Renal Vein Ureter Urinary bladder Urethra Renal hilus = area where blood vessels and nerves enter or exit kidney ANATOMY OF THE URINARY TRACT ${parentCitation.authFull}, Netter Collection of Medical Illustrations: Urinary System, The, SECTION 1, 1-28 Copyright © 2012 Copyright © 2012 by Saunders, an imprint of Elsevier Inc. Internal Anatomy of the Kidneys Three sections: 1. Renal capsule – outer membrane 2. Renal cortex – superficial layer 3. Renal medulla - inner region Nephron = urine forming functional unit of the kidneys, total number more than 1 million Elements of Renal Function Koeppen, Bruce M., MD, PhD, Berne and Levy Physiology, 33, 581-602 Copyright © 2018 Copyright © 2018 by Elsevier, Inc. All rights reserved. Tubular part of the nephron ends in the renal papilla Renal cortex Calyx Nephron Renal Pelvis urine Renal papilla Medulla Ureter Apex (narrower region of the pyramid) = renal papilla Scanning electron micrograph of papilla from a rat kidney (upper center), illustrating the area cribrosa formed by slit-like openings Pyramids Urine formed by each nephron is drained via the cribriform area in renal papillae, and further into calices, renal pelvis and ureter Anatomy of the Kidney Verlander, Jill W., Brenner and Rector's The Kidney, 2, 38-79.e12 Copyright © 2020 Copyright © 2020 by Elsevier, Inc. All rights reserved. Papilla and Calix The large collecting ducts (CD) are few in number as a result of fusion; they open into the calyx (C) at the papillary tip. At the papilla, the distal medulla consists almost entirely of large collecting ducts embedded in bulky interstitium (I) Urinary System Lowe, James S., BMedSci, BMBS, DM, FRCPath, Stevens & Lowe's Human Histology, Chapter 15, 286-318 Copyright © 2015 Copyright © 2015, 2005 by Mosby, an imprint of Elsevier Limited. All rights reserved. Calices = channels for urine collection into renal pelvis Urine formed by each nephron is drained via the renal papilla, and further into minor and major calices, renal pelvis and ureter ANATOMY OF THE URINARY TRACT ${parentCitation.authFull}, Netter Collection of Medical Illustrations: Urinary System, The, SECTION 1, 1-28 Copyright © 2012 Copyright © 2012 by Saunders, an imprint of Elsevier Inc. There are 5 to 14 minor calyces in each kidney (mean of 8, with 70% of kidneys having 7 to 9 minor calyces) Kidney stones frequently start their formation at the renal papilla and can obstruct flow of urine there or through other passages Renal cortex downward. Kidney stone Nephron Renal papilla Renal Pelvis Medulla urine Ureter Pyramids Renal Calculi or Nephrolithiasis Location and composition of kidney stones or urinari calculi vary: Ca++ oxalate, Ca++ phosphate, uric acid, cystine, etc. Asymptomatic when small in the kidney; frequently noted incidentally on abdominal imaging performed for unrelated reasons Acute renal colic occurs when a stone causes obstruction. Severe flank pain is a common presentation. Staghorn calculi impede filtration and can lead to end stage renal disease and postrenal azotemia. Kidneys, Ureters, and Urinary Bladder Buja, L. Maximilian, MD, Netter's Illustrated Human Pathology, Chapter 6, 173-224 Copyright © 2014 Copyright © 2014, 2005 by Saunders, an imprint of Elsevier Inc. Blood Supply of the Kidneys Adrenal Gland Renal Hilus Renal Artery Renal Vein Blood flow through the kidneys (0.5 % of body mass) is very high – 20-25% of the resting cardiac output Ureter Urinary bladder Urethra Renal arteries take blood to the renal parenchyma (tissue), mainly cortex ANATOMY OF THE URINARY TRACT ${parentCitation.authFull}, Netter Collection of Medical Illustrations: Urinary System, The, SECTION 1, 1-28 Copyright © 2012 Copyright © 2012 by Saunders, an imprint of Elsevier Inc. Renal cortex has a dense capillary network and high flow rate. Renal medulla (especially the inner part) has slow flow rate (vasa recta). ANATOMY OF THE URINARY TRACT ${parentCitation.authFull}, Netter Collection of Medical Illustrations: Urinary System, The, SECTION 1, 1-28 Copyright © 2012 Copyright © 2012 by Saunders, an imprint of Elsevier Inc. Renal parenchyma: Cortex C = high capillary density and blood flow Outer medulla: OS, outer stripe; IS, inner stripe. Inner medulla IM = low capillary density and blood flow (Modified from Kriz W, Lever AF: Renal countercurrent mechanisms: structure and function, Am Heart J 78:101-118, 1969; and Rollhäuser H, Kriz W, Heinke W: Das Gefässsystem der Rattenniere, Z Zellforsch 64:381-403, 1964.) Renal Structure and Function Pinsk, Maury N., Pediatric Critical Care, Chapter 66, 935-943 Copyright © 2011 Copyright © 2011, 2006, 1998, 1992 by Mosby, Inc., an affiliate of Elsevier Inc. Autonomic innervation of the kidneys and ureters Kidney has functionally important sympathetic innervation (release of renin, blood vessels tone) (Copyright 2016 Elsevier Inc. All rights reserved. www.netterimages.com .) Surgical, Radiologic, and Endoscopic Anatomy of the Kidney and Ureter Elkoushy, Mohamed Aly, MD, MSc, PhD, CampbellWalsh Urology, 42, 967-977.e2 Copyright © 2016 Section of renal parenchyma with numerous corpuscles Light micrograph with contrast showing blood supply to renal corpuscles Renal medicine—a call for papers Berman, Philippa, Lancet, The, Volume 385, Issue 9981, 1931-1931 Copyright © 2015 Dr Keith Wheeler/Science Photo Library Nephron I. Renal corpuscle: 2 parts Glomerulus – specialized capillary loops within Bowman’s capsule, double-walled epithelial cup which surrounds the glomerulus II. Renal tubule: 3 parts a. Proximal tubule b. Loop of Henle c. Distal tubule and collecting duct The Urinary System : Functional Anatomy and Urine Formation by the Kidneys Hall, John E., PhD, Guyton and Hall Textbook of Medical Physiology, Chapter 26, 323-333 Copyright © 2016 Copyright © 2016 by Elsevier, Inc. All rights reserved. Proximal tubule contains tubular fluid (filtrate) The proximal tubule is contiguous with the renal corpuscle and consists of a convoluted segment (pars convoluta) and a straight segment (pars recta). Most of solute transport occurs in the proximal tubules . Embryology and Normal Anatomy of the Kidney Raissian, Yassaman, MD, Practical Renal Pathology, 1, 1-14 Copyright © 2013 Copyright © 2013 by Saunders, an imprint of Elsevier Inc. Nephron Loop of Henle has descending and ascending limbs. Several distal tubules converge into a single collecting duct. As tubular fluid or filtrate flows along various parts, its composition changes. Several collecting ducts converge forming the papillary duct (duct of Bellini) at the end of which tubular fluid becomes urine. There are approximately 20 papillary ducts draining into each papilla. ANATOMY OF THE URINARY TRACT ${parentCitation.authFull}, Netter Collection of Medical Illustrations: Urinary System, The, SECTION 1, 1-28 Copyright © 2012 Copyright © 2012 by Saunders, an imprint of Elsevier Inc. Two Types of Nephrons: 1. Cortical (superficial) – glomerulus in the outer cortex, short loop of Henle, reaching into the outer medulla, only thick ascending limb. Outer medulla “salty” 2. Juxtamedullary – glomerulus next to medulla, thin and thick ascending limb, the loop is deep in the inner medulla. In humans, 85% of nephrons are cortical. Juxtamedullary nephrons are especially efficient in conserving water on occasions of dehydration. ANATOMY OF THE URINARY TRACT ${parentCitation.authFull}, Netter Collection of Medical Illustrations: Urinary System, The, SECTION 1, 1-28 Copyright © 2012 Copyright © 2012 by Saunders, an imprint of Elsevier Inc. Inner Medulla “very salty” Cortico-medullary osmotic gradient Osmolarity of the cortical renal tissue is about 290 mOsM. In the medulla, osmolarity is much higher, especially in the inner medulla (“very salty”) and can reach 1200 mOsM. This difference is called corticomedullary osmotic gradient. “salty” Inner Medulla “very salty” or papillary duct Organization of the Urinary System Giebisch, Gerhard, Medical Physiology, Chapter 33, 722-738.e1 Copyright © 2017 Copyright © 2017 by Elsevier, Inc. All rights reserved. Tubular and Vascular Components of the Nephron Postglomerular circulation of superficial and juxtamedullary nephrons. Note that the efferent arteriole gives rise to the peritubular capillaries in both cortical and juxtamedullary nephrons. The vasa recta form capillary networks that mainly surround the collecting ducts and limbs of Henle's loop of the juxtamedullary nephrons. FLUID AND ELECTROLYTE HOMEOSTASIS Kone, Bruce C., Pharmacology and Therapeutics: Principles to Practice, CHAPTER 10, 141-155 Copyright © 2009 Copyright © 2009 by Saunders, an imprint of Elsevier Inc. Nephron = Renal Corpuscle + Renal Tubule Two parts of renal corpuscle: 1. Glomerulus – specialized Blood In capillary loops 2. Bowman’s capsule – double-walled epithelial cup - surrounds the glomerulus - direct filtered plasma (filtrate) into the proximal renal tubule F Blood flows into the renal corpuscle for filtration via the afferent arteriole, efferent arteriole drains the glomerulus Glomerulus – blood filtration What is filtration F? Glomerular capillaries have high water permeability Blood Out ANATOMY OF THE URINARY TRACT ${parentCitation.authFull}, Netter Collection of Medical Illustrations: Urinary System, The, SECTION 1, 1-28 Copyright © 2012 Copyright © 2012 by Saunders, an imprint of Elsevier Inc. Tubular and Vascular Components of the Nephron 1. Glomerulus = the site for blood filtration, the 1st step in urine formation 2. Efferent arteriole gives rise to the peritubular capillaries, the site for reabsorption of substances (preventing their loss with urine) and secretion of other compounds (mostly those which are not needed) Space? The vasa recta form specialized peritubular capillary networks that surround the collecting ducts and limbs of Henle's loop in the juxtamedullary nephrons. Descending vasa recta Embryology and Normal Anatomy of the Kidney Raissian, Yassaman, MD, Practical Renal Pathology, 1, 1-14 Copyright © 2013 Copyright © 2013 by Saunders, an imprint of Elsevier Inc. Ascending vasa recta Portal system, a unique feature of the renal circulation: two capillary beds arranged in series. Two capillary beds: 1. Glomerular capillaries – filtration 2. Peritubular capillaries – reabsorption and secretion Each nephron has two sets of arterioles and capillary networks in series = portal system Embryology and Normal Anatomy of the Kidney Raissian, Yassaman, MD, Practical Renal Pathology, 1, 1-14 Copyright © 2013 Copyright © 2013 by Saunders, an imprint of Elsevier Inc. Urinary System Lowe, James S., BMedSci, BMBS, DM, FRCPath, Stevens & Lowe's Human Histology, Chapter 15, 286-318 Copyright © 2015 Copyright © 2015, 2005 by Mosby, an imprint of Elsevier Limited. All rights reserved. Three Processes of Urine Formation: filtration, reabsorption & secretion S Peritubular Capillaries Efferent Arteriole Proximal Tubule F R S Glomerular Capillaries Afferent Arteriole R Distal Tubule Thick Ascending Limb R S R F – filtration; R – reabsorption: from lumen to blood; S – secretion: from blood to lumen; E – excretion: passing urine to the bladder and external environment Collecting Duct Descending Limb R E Tubular reabsorption R Efferent Arteriole Afferent Arteriole – transport of substances across and between tubular epithelial cells from the lumen of renal tubule into the peritubular capillaries (reuptake of Blood substances to the blood, compare to absorption = addition) Bowmen’s capsule Tubular secretion S – F Lumen of renal tubule Tubular epithelial cells Balance Equation R S E E=F+S-R Peritubular transport of substances capillaries from the blood of the peritubular capillaries: drugs, toxins, wastes enter the filtrate. Excretion E - removal of a Renal vein substance from the body with urine Organization of the Urinary System Giebisch, Gerhard, Medical Physiology, Chapter 33, 722-738.e1 Copyright © 2017 Copyright © 2017 by Elsevier, Inc. All rights reserved. Plasma volume entering afferent arterioles = 100% Plasma volume exiting efferent arterioles = 80% How much of plasma is filtered in the glomerulus? Blood Filtration fraction Bowmen’s capsule Volume of F? about 20% Tubular epithelial cells Peritubular capillaries More than 19% of filtered volume is R reabsorbed Less than 1% of plasma E volume is excreted Interstitial space – right outside of capillaries (in this case peritubular) Renal vein More than 99% of plasma that enters kidney is reabsorbed How the Kidneys Handle Various Substances (average values) Substance Amount filtered per day Amount excreted per day Percent reabsorbed Water, L 180 1.8 99.0 Sodium, g 630 3.2 99.5 Bicarbonate 264 2.6 99.0 Glucose, g 180 0 100 Urea, g 54 27 50 Potassium, g 28 3.9 86 Phosphate, g 18 2.2 88 Inulin * * 0 * depends on the amount injected Handling of each substance is a particular combination of filtration, reabsorption and secretion What is plasma? Filtered Load and Excretion Rate Filtration: filtered load – mass of substance z filtered per minute. filtered load = GFR x Pz, where Pz – plasma concentration of substance z Excretion: excretion rate – mass of substance z excreted per minute. excretion rate = UF x Uz, where Uz – urine concentration of substance z, UF – flow of urine Renal Physiology ${parentCitation.authFull}, Physiology, 6, 239-302 Copyright © 2014 Copyright © 2014 by Saunders, an imprint of Elsevier Inc. How to tell if a substance is secreted or reabsorbed? Excretion = Filtration – Reabsorption + Secretion If substance is only filtered: Filtered load = Excretion rate If Filtred load > Excretion (rate) – reabsorption occurred If Filtered load < Excretion (rate) – secretion occurred Renal Physiology ${parentCitation.authFull}, Physiology, 6, 239-302 Copyright © 2014 Copyright © 2014 by Saunders, an imprint of Elsevier Inc. Filtration, Excretion and Plasma Clearance Efferent arteriole Afferent arteriole Peritubular capillaries Renal vein Sample of Plasma Afferent arteriole Renal vein Afferent arteriole Renal vein Afferent arteriole Renal vein …… Renal plasma clearance – volume of plasma cleared from a substance in a unit of time, rate of elimination of a substance from the vascular system by the kidney Is E always = to Cl? Filtration, Excretion and Plasma Clearance Efferent arteriole Renal plasma clearance is decreased if reabsorption rises. Afferent arteriole Renal plasma clearance is increased if filtration and/or secretion rise. Renal plasma clearance = filtration + secretion – reabsorption! Renal Handling of Glutamine (G) in Chronic Acidosis Afferent Arteriole Glomerulus Efferent Arteriole G In chronic metabolic acidosis, the kidneys act as a major sink for glutamine because of elevated transport of this amino acid into the renal epithelial cells and sustained extraction from the blood (i. e. high renal plasma clearance). High uptake of glutamine into the renal epithelium does not lead to high glutamine excretion (E) in urine! Why? G G Renal G Epithelial Cells Glu NH3 G + Peritubular H+ G Capillaries Glu G NH4+ E Glutamine (G) is filtered into the renal tubule and reabsorbed in the renal epithelial cells, where it is enzymatically converted into G glutamate (Glu) with a release of ammonium (NH3) into the lumen. NH3 combines with H+ and forms ammonium ion NH4+ destined to be excreted in urine (important physiological adaptation in acid base balance maintenance) G secreted from the peritubular capillaries is also converted to Glu in the epithelium. As a result of the conversion to Glu, G may barely appear in urine in acidosis, and its excretion may be 0 (!) despite high renal plasma clearance! Cl Renal vein Renal excretion (E) and renal plasma clearance (Cl) reflect two different not always congruent in % processes!