The Renal Circulation in Shock
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Role of New Podocyte-Associated Proteins in the Renal Ultrafiltration Barrier
From the DEPARTMENT OF LABORATORY MEDICINE Karolinska Institutet, Stockholm, Sweden ROLE OF NEW PODOCYTE-ASSOCIATED PROTEINS IN THE RENAL ULTRAFILTRATION BARRIER Angelina Schwarz Stockholm 2019 All previously published papers were reproduced with permission from the publisher. Published by Karolinska Institutet. Printed by Universitetsservice US-AB 2019. © Angelina Schwarz, 2019 ISBN 978-91-7831-452-2 Cover: confocal microscopy image of a mouse glomerulus (front) and electron microscopy image of a podocyte (back) Role of new podocyte-associated proteins in the renal ultrafiltration barrier THESIS FOR DOCTORAL DEGREE (Ph.D.) By Angelina Schwarz Principal Supervisor: Opponent: Assoc. Prof. Jaakko Patrakka, MD, PhD Prof. Rachel Lennon, MD, PhD Karolinska Institutet University of Manchester Department of Laboratory Medicine School of Biological Sciences Division of Pathology/ICMC Division of Cell Matrix and Regenerative Medicine Co-supervisor(s): Lwaki Ebarasi, PhD Examination Board: Karolinska Institutet Assoc. Prof. Sergiu-Bogdan Catrina, MD, PhD Department of Laboratory Medicine Karolinska Institutet Division of Pathology/ICMC Department of Molecular Medicine and Surgery Division of Growth and Metabolism Mark Lal, PhD AstraZeneca Prof. Bengt Fellström, MD, PhD Bioscience, Cardiovascular, Renal and Uppsala University Metabolism, Innovative Medicines Biotech Unit Department of Medical Sciences Division of Nephrology Assoc. Prof. Taija Mäkinen, PhD Uppsala University Department of Immunology, Genetics and Pathology Division of Vascular Biology ABSTRACT Chronic kidney disease (CKD) is a major health problem and an economical burden affecting people worldwide. The main causes of CKD are diabetes and hypertension and patient numbers keep increasing. In many cases, CKD is progressive leading to end stage renal disease (ESRD), a condition that can be treated only through chronic dialysis or renal transplantation. -
ANSWER KEY Integrative Sciences: Biological Systems B Body Fluid/Electrolytes and Kidney Systems
ANSWER KEY Integrative Sciences: Biological Systems B Body Fluid/Electrolytes and Kidney Systems Problem Set Review Monday, November 28, 2011 at 9 am Lecturer: Lisa M Harrison-Bernard, PhD I. Body Fluid Problems - Shifts of water between compartments What happens to the following 5 parameters: ECF volume? ICF volume? ECF osmolarity? Plasma protein concentration (PPC)? Blood pressure? A. Infusion of isotonic NaCl (isosmotic volume expansion) B. Diarrhea - loss of isotonic fluid (isosmotic volume contraction) C. Excessive NaCl intake - addition of NaCl (hyperosmotic volume expansion) D. Sweating in a desert - loss of water (hyperosmotic volume contraction) E. Syndrome of inappropriate antidiuretic hormone (SIADH) - gain of water (hypoosmotic volume expansion) F. Adrenocortical insufficiency - loss of NaCl (hypoosmotic volume contraction) Page 1 of 5 ECF ICF ECF PPC (g%) Blood Volume (L) Volume (L) Osmolarity Pressure (mOsm) (mmHg) A ⇑ ⇔ ⇔ ⇓ ⇑ B ⇓ ⇔ ⇔ ⇑ ⇓ C ⇑ ⇓ ⇑ ⇓ ⇑ D ⇓ ⇓ ⇑ ⇑ ⇓ E ⇑ ⇑ ⇓ ⇓ ⇑ F ⇓ ⇑ ⇓ ⇑ ⇓ Page 2 of 5 II. Starling Forces 1. At the afferent arteriolar end of a glomerular capillary, PGC is 45 mmHg, PBS is 10 mmHg, and πGC is 27 mmHg. What are the value and direction of the net ultrafiltration pressure? PUF = (PGC – PBS) – (πGC - πBS) PUF = (45 - 10 mmHg) – (27) = 8 mmHg favors filtration of fluid out of the glomerular capillary III. Renal Clearance, Renal Blood Flow, Glomerular Filtration Rate 2. To measure GFR: Infuse inulin intravenously until PIN is stable. Measure urine volume produced in a known period of time (urine flow). Measure PIN and UIN. Given the following: PIN = 0.5 mg/ml UIN = 60 mg/ml Urine flow = 1.0 ml/min Calculate GFR? GFR = CIN = (UIN)(UV) ÷ PIN GFR = (60 mg/ml) (1 ml/min) ÷ (0.5 mg/ml) = 120 ml/min 3. -
Renal Function in Primary Aldosteronism
RENAL FUNCTION IN PRIMARY ALDOSTERONISM Harriet P. Dustan, … , A. C. Corcoran, Irvine H. Page J Clin Invest. 1956;35(12):1357-1363. https://doi.org/10.1172/JCI103392. Research Article Find the latest version: https://jci.me/103392/pdf RENAL FUNCTION IN PRIMARY ALDOSTERONISM 1 By HARRIET P. DUSTAN, A. C. CORCORAN, AND IRVINE H. PAGE (From the Research Division of The Cleveland Clinic Foundation and The Frank E. Bunts Educational Institute, Cleveland, 0.) (Submitted for publication June 11, 1956; accepted August 9, 1956) Primary aldosteronism is characterized by weak- purate (PAH) and mannitol. Total renal vascular re- ness-a sequel to potassium loss; hypertension- sistance was calculated by the formula of Gomez (3). The functions of water conservation and electrolyte ex- attributed to sodium retention; thirst and polyuria; cretion were observed simultaneously. Water con- and excretion of dilute, alkaline urine (1). These servation was determined from the differences (TVio) defects imply significant changes in renal function. between urine flow (V) and osmolal clearance (Co..) The purpose of this report is to describe pre- (4) during osmotic diuresis in hydropenia (water depri- and postoperative observations of renal function vation for 16 or 24 hours and/or infusion of Pitressin@). The priming solution contained 260 mOsm. of mannitol in three patients suffering from aldosterone-se- and 0.6 gin. of PAH; the sustaining infusion supplied creting adrenal cortical tumors. about 3 mOsm. of mannitol and 15 mg. per PAH per min- The data indicate that excess urinary potassium ute. Urine formed during the first 20 minutes was dis- excretion is attributable to aldosteronism as such, carded; it was then collected from an indwelling urethral and may bear on the basic cellular mechanism of catheter at 3 to 6 successive intervals of about 10 min- action of aldosterone. -
Renal Hemodynamic and Metabolic Physiology in Normal Pregnancy
Obstetric Nephrology: Renal Hemodynamic and Metabolic Physiology in Normal Pregnancy Ayodele Odutayo and Michelle Hladunewich Summary Glomerular hyperfiltration, altered tubular function, and shifts in electrolyte-fluid balance are among the hallmark renal physiologic changes that characterize a healthy pregnancy. These adjustments are not only critical to maternal and fetal well being, but also provide the clinical context for identifying gestational aberrations in Divisions of Nephrology and renal function and electrolyte composition. Systemic vasodilation characterizes early gestation and produces Obstetric Medicine, increments in renal plasma flow and GFR, the latter of which is maintained into the postpartum period. In addition, Department of renal tubular changes allow for the accumulation of nutrients and electrolytes necessary for fetal growth such that Medicine, wasting of proteins, glucose, and amino acids in urine is limited in pregnancy and total body stores of electrolytes Sunnybrook Health increase throughout gestation. Substantial insight into the mechanisms underlying these complex adjustments can Sciences Centre, University of Toronto, be gleaned from the available animal and human literature, but our understanding in many areas remains Toronto, Ontario, incomplete. This article reviews the available literature on renal adaptation to normal pregnancy, including renal Canada function, tubular function, and electrolyte-fluid balance, along with the clinical ramifications of these adjust- ments, the limitations of the existing literature, and suggestions for future studies. Correspondence: Clin J Am Soc Nephrol 7: 2073–2080, 2012. doi: 10.2215/CJN.00470112 Dr. Michelle Hladunewich, Divisions of Nephrology, Critical Introduction clinically presents as a decrease in the serum creati- Care, and Obstetric Maternal accommodation to normal pregnancy begins nine. -
Ward's Renal Lobule Model
Ward’s Renal Lobule Model 470029-444 1. Arcuate artery and vein. 7. Descending thick limb of 12. Collecting tubule. 2. Interlobular artery and vein. Henle's loop. 13. Papillary duct of Bellini. 3. Afferent glomerular arteriole. 8. Thin segment of Henle's 14. Vasa recta. loop. 4. Efferent glomerular arteriole. 15. Capillary bed of cortex (extends 9. Ascending thick limb of through entire cortex). 5. Renal corpuscle (glomerulus Henle's loop. plus Bowman's capsule). 10. Distal convoluted tubule. 16. Capillary bed of medulla (extends 6. Proximal convoluted tubule. 11. Arched connecting tubule. through entire medulla). MANY more banks of glomeruli occur in the cortex than are represented on the model, and the proportionate length of the medullary elements has been greatly reduced. The fundamental physiological unit of the kidney is the nephron, consisting of the glomerulus, Bowman's capsule, the proximal convoluted tubule, Henle's loop, and the distal convoluted tubule. The blood is filtered in the glomerulus, water and soluble substances, except blood proteins, passing into Bowman's capsule in the same proportions as they occur in the blood. In the proximal tubule water and certain useful substances are resorbed from the provisional urine, while some further components may be added to it by secretory activity on the part of the tubular epithelium. In the remainder of the tubule, resorption of certain substances is continued, while the urine is concentrated further by withdrawal of water. The finished urine flows through the collecting tubules without further change. Various kinds of loops occur, varying in length of the thin segment, and in the level to which they descend into the medulla. -
Glomerular Filtration I DR.CHARUSHILA RUKADIKAR Assistant Professor Physiology GFR 1
Glomerular filtration I DR.CHARUSHILA RUKADIKAR Assistant Professor Physiology GFR 1. Definition 2. Normal value 3. Variation 4. Calculation (different pressures acting on glomerular membrane) 5. Factors affecting GFR 6. Regulation of GFR 7. Measurement of GFR QUESTIONS LONG QUESTION 1. GFR 2. RENIN ANGIOTENSIN SYSTEM SHORT NOTE 1. DYNAMICS OF GFR 2. FILTRATION FRACTION 3. ANGIOTENSIN II 4. FACTORS AFFECTING GLOMERULAR FILTRATION RATE 5. REGULATION OF GFR 6. RENAL CLEARANCE TEST 7. MEASUREMENT OF GFR Collecting duct epithelium P Cells – Tall, predominant, have few organelles, Na reabsorption & vasopressin stimulated water reabsorption I cells- CT and DCT, less, having more cell organelles, Acid secretion and HCO3 transport CHARACTERISTICS OF RENAL BLOOD FLOW 600-1200 ml/min (high) AV O2 difference low (1.5 mL/dL) During exercise increases 1.5 times Low basal tone, not altered in denervated / innervated kidney VO2 in kidneys is directly proportional to RBF, Na reabsorption & GFR Not homogenous flow, cortex more & medulla less Vasa recta hairpin bend like structure, hyperosmolarity inner medulla Transplanted kidney- cortical blood flow show autoregulation & medullary blood flow don’t show autoregulation, so no TGF mechanism Neurogenic vasodilation not exist 20% of resting cardiac output, while the two kidneys make < 0.5% of total body weight. Excretory function rather than its metabolic requirement. Remarkable constancy due to autoregulation. Processes concerned with urine formation. 1. Glomerular filtration, 2. Tubular reabsorption and 3. Tubular secretion. • Filtration Fluid is squeezed out of glomerular capillary bed • Reabsorption Most nutrients, water and essential ions are returned to blood of peritubular capillaries • Secretion Moves additional undesirable molecules into tubule from blood of peritubular capillaries Glomerular filtration Glomerular filtration refers to process of ultrafiltration of plasma from glomerular capillaries into the Bowman’s capsule. -
Active Transport, Hematology, EKG and Urinalysis Author: Margaret T. F
FINAL PROBLEM SET: Integration of Material from 4 Labs; Active Transport, Hematology, EKG and Urinalysis Author: Margaret T. Flemming, MS, Department of Biology, Austin Community College, Austin, TX Objectives—after completing this problem set you should be able to: 1) calculate renal function values, showing your work 2) describe the relationship between cardiac and renal function 3) describe the relationship between blood values and urine values, including relevant information regarding secondary active transport of glucose by the renal tubules Background—Renal function calculations can give a good snapshot of a patient’s health, indicating possible circulatory problems, blood glucose problems, etc. But being able to do the calculations is only the first step. This problem set asks you to do calculations and then think critically to analyze results and come up with possible diagnoses. To successfully answer the critical thinking questions you will need to integrate what you know about renal function, active transport, and normal blood and urine values. In addition, you’ll need to bring in what you know about normal cardiac output (CO), renal fraction of CO and how the kidney adjust to changes in CO and blood pressure. Resources—Work in your regular lab groups of 3-4 students. Definitions and formulas are given to you, along with certain clinical values that were not obtained in labs. Chapters 5, 15 and 16 and 19 in your text (Human Physiology, Silverthorn, 4th Ed.), as well as in your notes for those chapters, provide the background information needed to answer the theoretical questions. Remember to limit your online searches to sites ending in edu, or sites of professional organizations, rather than commercial sites. -
L25 Kidney2 to Post
Vert Phys PCB3743 Kidney 1 Fox Chapter 17 part 1 © T. Houpt, Ph.D. 1 Kidney Function Remove waste chemicals, while reabsorbing nutrients 1. Filter plasma from blood (including water & water-soluble nutrients) 2. Reabsorb Na+ : essential to maintain high extracellular [Na+] 3. Reabsorb H20 : essential to maintain body fluid volume 4. Reabsorb glucose and other nutrients 5. Reabsorb HCO3 / secrete H+ to maintain pH 2 Toxicity of Ammonia (NH3) 1. NH3 -> NH4+ very basic 2. NH3 is metabolic poison • Fish allow NH3 to diffuse into surrounding water • Birds & Reptiles convert NH3 to uric acid, which is not water soluble and is excreted in the feces. • Mammals convert NH3 to urea (CH4N2O), which is non-toxic and water soluble for excretion by kidney 1828: first organic synthesis: the production of urea without living tissue. → AgNCO + NH4Cl (NH2)2CO + AgCl 3 Krebs Cycle http://hyperphysics.phy-astr.gsu.edu/hbase/biology/tca.html 4 Too much ammonia removes a-ketoglutarate from Krebs cycle, so starves cells of ATP http://www.ucl.ac.uk/~ucbcdab/urea/amtox.htm 5 Urea - waste product of excess amino acid metabolism amino acid metabolism toxic! 2 liver ammonia + CO 6 Chapter 17: Anatomy of the Kidney Kidney Function Filter excess and waste chemicals (water soluble) from the blood. (excess water, Na+, urea, glucose > 200 mg/100ml) Kidney Structures cortex (bark): reddish brown, lots of capillaries medulla (inner region): striped with capillaries & collecting ducts; divided into renal pyramids urine -> collecting ducts -> minor calyces -> major calyces calyx; calyces -> renal pelvis-> ureters -> urinary bladder -> urethra “cup” high surface area for exchange, then to storage and outside ren- Latin for kidney nephro- Greek for kidney -uria - problem with urine, e.g. -
The Distal Convoluted Tubule and Collecting Duct
Chapter 23 *Lecture PowerPoint The Urinary System *See separate FlexArt PowerPoint slides for all figures and tables preinserted into PowerPoint without notes. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Introduction • Urinary system rids the body of waste products. • The urinary system is closely associated with the reproductive system – Shared embryonic development and adult anatomical relationship – Collectively called the urogenital (UG) system 23-2 Functions of the Urinary System • Expected Learning Outcomes – Name and locate the organs of the urinary system. – List several functions of the kidneys in addition to urine formation. – Name the major nitrogenous wastes and identify their sources. – Define excretion and identify the systems that excrete wastes. 23-3 Functions of the Urinary System Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Diaphragm 11th and 12th ribs Adrenal gland Renal artery Renal vein Kidney Vertebra L2 Aorta Inferior vena cava Ureter Urinary bladder Urethra Figure 23.1a,b (a) Anterior view (b) Posterior view • Urinary system consists of six organs: two kidneys, two ureters, urinary bladder, and urethra 23-4 Functions of the Kidneys • Filters blood plasma, separates waste from useful chemicals, returns useful substances to blood, eliminates wastes • Regulate blood volume and pressure by eliminating or conserving water • Regulate the osmolarity of the body fluids by controlling the relative amounts of water and solutes -
Renal Physiology and Pathophysiology of the Kidney
Renal Physiology and pathophysiology of the kidney Alain Prigent Université Paris-Sud 11 IAEA Regional Training Course on Radionuclides in Nephrourology Mikulov, 10–11 May 2010 The glomerular filtration rate (GFR) may change with - The adult age ? - The renal plasma (blood) flow ? + - The Na /water reabsorption in the nephron ? - The diet variations ? - The delay after a kidney donation ? IAEA Regional Training Course on Radionuclides in Nephrourology Mikulov, 10–11 May 2010 GFR can measure with the following methods - The Cockcroft-Gault formula ? - The urinary creatinine clearance ? - The Counahan-Baratt method in children? - The Modification on Diet in Renal Disease (MDRD) formula in adults ? - The MAG 3 plasma sample clearance ? IAEA Regional Training Course on Radionuclides in Nephrourology Mikulov, 10–11 May 2010 About the determinants of the renogram curve (supposed to be perfectly « BKG » corrected) 99m -The uptake (initial ascendant segment) of Tc DTPA depends on GFR 99m -The uptake (initial ascendant segment) of Tc MAG 3 depends almost only on renal plasma flow 123 -The uptake (initial ascendant segment) of I hippuran depends both on renal plasma flow and GFR -The height of renogram maximum (normalized to the injected activity) reflects on the total nephron number -The « plateau » pattern of the late segment of the renogram does mean obstruction ? IAEA Regional Training Course on Radionuclides in Nephrourology Mikulov, 10–11 May 2010 Overview of the kidney functions Regulation of the volume and composition of the body fluids -
Mechanism of the Antidiuretic Effect Associated with Interruption of Parasympathetic Pathways
Mechanism of the Antidiuretic Effect Associated with Interruption of Parasympathetic Pathways Robert W. Schrier, … , Tomas Berl, Judith A. Harbottle J Clin Invest. 1972;51(10):2613-2620. https://doi.org/10.1172/JCI107079. Research Article The present experiments were undertaken to investigate the mechanism whereby the parasympathetic nervous system may be involved in the renal regulation of solute-free water excretion. The effects of interruption of parasympathetic pathways by bilateral cervical vagotomy were examined in eight normal and seven hypophysectomized anesthetized dogs undergoing a water diuresis. In the normal animals cervical vagotomy decreased free-water clearance (C ) from H2O 2.59±0.4 se to −0.26±0.1 ml/min (P < 0.001), and urinary osmolality (Uosm) increased from 86±7 to 396±60 mOsm/kg (P < 0.001). This antidiuretic effect was not associated with changes in cardiac output, renal perfusion pressure, glomerular filtration rate, renal vascular resistance, or filtration fraction and was not affected by renal denervation. A small but significant increase in urinary sodium and potassium excretion was observed after vagotomy in these normal animals. Pharmacological blockade of parasympathetic efferent pathways with atropine, curare, or both was not associated with an alteration in either renal hemodynamics or renal diluting capacity. In contrast to the results in normal animals, cervical vagotomy was not associated with an antidiuretic effect in hypophysectomized animals. C was 2.29±0.26 ml/min H2O before and 2.41±0.3 ml/min after vagotomy, and Uosm was 88±9.5 mOsm/kg before vagotomy and 78±8.6 mOsm/kg after vagotomy in the hypophysectomized animals. -
The Kidney: a Designed System for Plasma Homeostasis
The Proceedings of the International Conference on Creationism Volume 3 Print Reference: Pages 505-512 Article 50 1994 The Kidney: A Designed System for Plasma Homeostasis Patricia L. Speck Follow this and additional works at: https://digitalcommons.cedarville.edu/icc_proceedings DigitalCommons@Cedarville provides a publication platform for fully open access journals, which means that all articles are available on the Internet to all users immediately upon publication. However, the opinions and sentiments expressed by the authors of articles published in our journals do not necessarily indicate the endorsement or reflect the views of DigitalCommons@Cedarville, the Centennial Library, or Cedarville University and its employees. The authors are solely responsible for the content of their work. Please address questions to [email protected]. Browse the contents of this volume of The Proceedings of the International Conference on Creationism. Recommended Citation Speck, Patricia L. (1994) "The Kidney: A Designed System for Plasma Homeostasis," The Proceedings of the International Conference on Creationism: Vol. 3 , Article 50. Available at: https://digitalcommons.cedarville.edu/icc_proceedings/vol3/iss1/50 THE KIDNEY: A DESIGNED SYSTEM FOR PLASMA HOMEOSTASIS PATRICIA L SPECK, DVM RT. 1, BOX 164 B McARTHUR, OHIO, 45651 KEYWORDS active transport. ADH. afferent. aldosterone. brush border. capsule. concentration gradient. convoluted tubule. cortex, design, dialysis, efferent, glomerulus, hairpin loop, homeostasis, integration, juxtaglomerular apparatus, kidney, macula densa, medulla, metanephros, nephron, osmolality, permeability, purpose, reabsorption, renin, secretion, sodium cycle, symmetry, urea cycle, vasa recta ABSTRACT The kidney is an excellent biochemical model showing design in nature. Design implies a designer. The development of the kidney follows a very precise pattern and time schedule.