Introduction to the Kidney (Warwick University) PDF

Introduction to the Kidney Dr Mark Richards [email protected] Acknowledgements to Dr Nick Hopcroft & Dr Jamie Roebuck  Learning Outcomes By the end of this session, you should be able to: 1. List the main functions of the kidney 2. List the component p...

Introduction to the Kidney Dr Mark Richards [email protected] Acknowledgements to Dr Nick Hopcroft & Dr Jamie Roebuck  Learning Outcomes By the end of this session, you should be able to: 1. List the main functions of the kidney 2. List the component parts of the uriniferous tubule and explain their main functions 3. Integrate an understanding of the microanatomical structure of the urinary system with its physiological function 4. Describe the microscopic appearance of the system 5. Apply the basic principles of cell structure and function to cells of the urinary tract 6. Define the composition of body fluids and describe how they are distributed in body compartments Functions of the Kidney 1.Excretion of metabolic waste and toxins 2.Regulation of body fluid volume 3.Regulation of body fluid composition 4.Endocrine functions Structure of kidneys (macro and micro) reflects their functions Key processes are filtration, reabsorption and secretion to eventually form urine which is excreted N.B. Texts/individuals differ with how they group / list kidney functions LO: 1 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780702073373000146#hl00015 Image: Guyton & Hall Textbook of Medical Physiology  Epithelial Tissue 1 What are the four other tissue types apart from epithelial tissue? Give three functions of epithelial tissue relevant to the kidneys How is epithelial tissue classified and named? How do the different functions of epithelial tissue relate to the different structural classifications? LO: 5 See Kidney and Urinary Tract Histology Lt workbook  Epithelial Tissue 2 1. Layers Simple or stratified 2. Shape Flat = squamous Square = cuboid Rectangular = columnar 3. Specialisations Microvilli, cilia, mucoid glands, keratin… Epithelial tissue in the kidney are specialised for the key processes of filtration, absorption and secretion LO: 5 See Kidney and Urinary Tract Histology Lt workbook  Kidney Macrostructure Minor Calyx Cortex Major Calyx Medulla Renal pyramid Renal Artery Renal Vein Renal Papilla Renal pelvis Ureter LO: 3, 4 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780702073373000146#hl00016  Kidney Microstructure 1 CORTE X Kidney made up of numerous uriniferous tubules and associated Renal MEDUL pyram blood vessels LA id Renal papilla LO: 3, 4 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780702073373000146#hl00017 Image: Netter’s Essential Histology (2e) -  Kidney Microstructure 2 Uriniferous tubule = nephron + CORTE collecting duct X Nephr Nephron is functional on unit of kidney ~1 million per kidney Urinifero us Many nephrons drain tubule into same collecting MEDUL Collecti duct LA ng duct N.B. Texts differ slightly with definition / naming of different parts of uriniferous tubule Renal papilla LO: 2 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780702073373000146#hl00017 Image: Netter’s Essential Histology (2e) -  Uriniferous Tubule Renal corpusc Proximal le tubule CORTE Distal X tubule Loop of Henle Collecti ng duct MEDUL LA Nephron = renal corpuscle + proximal (convoluted) tubule (PT) + Loop of Henle + distal (convoluted) tubule (DT) Cortex - mostly renal corpuscles, PT and DT Medulla - mostly Loops of Henle and Nephrons referred to as cortical (~80%) or juxtamedullary (~20%) depending on collecting ducts position of renal corpuscle LO: 2 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780702073373000146#hl00017 Image: Netter’s Essential Histology (2e) -  Overview of Microstructure Proximal tubule Renal corpuscle Uriniferous Distal tubule tubule Nephron + Loop of Henle Collecting duct Collecting duct Renal corpuscle + Proximal (convoluted) tubule + Glomerulus Loop of Henle + + Bowman’s Distal (convoluted) capsule LO: 2 tubule Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780702073373000146#hl00017 Image: Netter’s Essential Histology (2e) -  Blood Supply to Kidneys 1 Interlobar arteries Arcuate arteries run along corticomedullary Renal junction artery Segme Interlobular ntal arteries give off arteries afferent arterioles to the renal corpuscles LO: 3 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780702073373000146#hl00017 Image: Netter’s Essential Histology (2e) -  Blood Supply to Kidneys 2 Efferent Peritubular arteriole Glomerular capillaries (high capillaries (low pressure) Afferent pressure) arteriole Interlobular artery (& vein) CORTE Arcuate artery (& X vein) Blood to kidney passes Vasa through TWO capillary recta (low beds pressure) High pressure glomerular MEDUL capillaries (filtration) LA Low pressure peritubular capillaries (reabsorption / secretion) LO: 3 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780702073373000146#hl00017 Image: Guyton & Hall Textbook of Medical Physiology  Renal Corpuscle Renal corpuscle made up of glomerulus (glomerular capillaries) and Bowman’s capsule Vascular Filters blood to form an initial filtrate pole Bowman’s capsule like a double Blood walled cup that surrounds glomerular capillaries Outer layer = Parietal layer Containment → Simple squamous Inner layer = Visceral layer Filtration → Modified simple squamous Filtrate (podocytes) Mesangial cells provide support between the glomerular Note: Arteriole capillary at either end of glomerular Urinary capillary bedloops – allows high pressure for LO: 3 pole filtration Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780702073373000146#hl00017 Images: Guyton & Hall Textbook of Medical Physiology (13e) – Hall  Filtration Podocytes wrap around the Barrier glomerular capillaries and their interlinked foot processes form filtration slits Filtration barrier formed by: 1. Glomerular capillary endothelium (fenestrated) 2. Basement membrane (negatively charged) 3. Epithelial cells (podocytes) (interdigitating foot processes & filtration slits) Limits passage of substances from blood based on their size, charge and shape LO: 3, 4, 5 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780702073373000146#hl00017 Images: Guyton & Hall Textbook of Medical Physiology  Take a break! Kidney Bingos by Wire https://www.youtube.com/watch?v=6Orx Q5cKaOQ  Nephron – simplified form LO: 3, 4 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780702073373000146#hl00017 Image: Guyton & Hall Textbook of Medical Physiology  Proximal (Convoluted) Tubule Unmodified filtrate leaves Bowman’s space and enters the proximal convoluted tubule Majority of water, sodium, chloride, amino acids, glucose reabsorption takes place here Secretion of some drugs and waste molecules Simple cuboidal cells with microvilli forming a ‘brush border’ to increase surface area LO: 3, 4, 5 Clinicalkey: Images: Medical Sciences (2e) – Naish https://www.clinicalkey.com/student/content/book/3-s2.0-B9780702073373000146#hl00017 Guyton & Hall Textbook of Medical Physiology  Three main parts with Loop of Henle different characteristics Thick ascending limb – impermeable to water Thin descending limb – permeable to water - Active reabsorption of no active reabsorption sodium and other solutes or secretion of solutes Simple cuboidal cells Thin ascending limb – impermeable to water Essentially no active reabsorption or secretion of solutes Net effect is to generate Both thin parts have a hyperosmolar simple squamous interstitium in epithelium medulla – important in concentration of urine LO: 3, 4, 5 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780702073373000146#hl00017 Images: Medical Sciences (2e) – Naish 45 Guyton & Hall Textbook of Medical Physiology  Distal (Convoluted) Tubule Divided into early and late parts Active reabsorption of sodium and other solutes; secretion of potassium and hydrogen ions Simple cuboidal cells Variable water permeability depending on precise part of distal tubule and presence of antidiuretic hormone (ADH) Early distal tubule passes back to the vascular pole of its own renal corpuscle to form part of juxtaglomerular apparatus LO: 3, 4, 5 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780702073373000146#hl00017 Images: Medical Sciences (2e) – Naish 61 Guyton & Hall Textbook of Medical Physiology  Juxtaglomerular Apparatus (JGA) Distal tubule Macula Three components to JGA:- Lacis cells densa 1. Macula densa - specialised cells within part of early Afferen t Effere distal tubule that passes nt arteriol next to vascular pole of its Granular e arteri own renal corpuscle cells ole 2. Extraglomerular mesangial cells (Lacis cells) 3. Granular or juxtaglomerular cells in afferent arteriole Involved in tubuloglomerular feedback (see later Glomerular LO: 3, 4, 5 lectures) and control of capillaries Clinicalkey: blood pressure https://www.clinicalkey.com/student/content/book/3-s2.0-B9780702073373000146#hl00029 Images: Medical Sciences (2e) –  Collecting Duct (Medullary) Final site for urine processing Water permeability of this part of nephron under hormonal control by antidiuretic hormone (ADH) Surrounded by a medullary interstitium with a high concentration of solutes Key role in regulating degree of urine concentration Simple columnar cells LO: 3, 4, 5 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780702073373000146#hl00017 Images: Medical Sciences (2e) – Naish 64 Guyton & Hall Textbook of Medical Physiology Test Your Knowledge – Intro to the kidney 1. Name the four functions of the kidney. 2. Which part of the nephron tubule is closely associated with the juxtaglomerular apparatus? 3. What are the three components that form the filtration barrier in the renal corpuscle? 4. What type of epithelial cells line the proximal convoluted tubule? What specialised properties do these epithelial cells have? 5. The loop of Henle has a major role in determining urine concentration by influencing the osmolarity of the medullary interstitium. Is the medullary interstitium hyposmolar, isoosmolar or hyperosmolar? The Kidney The Headlines! functional 3 key unit of the processes epithelial layers are adapted kidney is Filtration for the functional role in the Reabsorption different parts of the nephron nephron Secretion The renal corpuscle has a filtration barrier: Fenestrated vascular The kidney has a unique endothelium arrangement of capillaries Negatively charged basement associated with the nephron High pressure glomerular membrane Each Specialised component epithelium of the - capillaries Low pressure peritubular nephron’s Podocytestubular system have different properties reflecting capillaries The juxtaglomerular their functional role. apparatus provides a feedback system between the tubular system and the vascular system This Photo by Unknown Author is licensed under CC BY-SA  Body Fluid Homeostasis Volume & Composition Body Fluid Homeostasis Maintaining a constant volume and stable composition of body fluids essential for homeostasis Precise matching of intake and output Insensible water losses (poorly regulated) Kidneys play major role in regulation of body fluid volume and composition LO: 6 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323793339000158#hl00016 Image: Guyton & Hall Textbook of Medical Physiology  Body Fluid Compartments 1 In 70kg male total body water is 42 litres i.e. ~60% bodyweight Varies with age, sex, body fat Distributed in different compartments separated by semi permeable membranes Intracellular fluid (ICF) = 28 litres i.e. fluid in the cells LO: 6 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323793339000158#hl00016 Image: Guyton & Hall Textbook of Medical Physiology Body Fluid Compartments 2 ECF has two main compartments Interstitial fluid (~11 litres) which surrounds the cells Plasma (~3 litres) which is non-cellular component of blood Composition of body fluids varies between compartments LO: 6 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323793339000158#hl00016 Image: Guyton & Hall Textbook of Medical Physiology Body Fluid Composition 1 Capillary membrane highly permeable to water and electrolytes but not to most plasma proteins Interstitial fluid and plasma have similar compositions apart from proteins which remain in plasma Cell membrane permeable to water but not to most electrolytes LO: 6 Clinicalkey: https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323793339000158#hl00016 Image: Guyton & Hall Textbook of Medical Physiology  Body Fluid Composition 2 ECF Sodium is the main cation (+ve) Chloride is the main anion (-ve) ICF Potassium is the main cation (+ve) Phosphate is the main anion (-ve) Different compartments LO: 6 are in osmotic Clinicalkey: equilibrium https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323793339000158#hl00016 85 Image: Guyton & Hall Textbook of Medical Physiology Test Your Knowledge – Body fluid composition The ICF constitutes about: A. 40% total body weight B. 80% total body weight C. 20% total body weight D. 50% total body weight E. 10% total body weight The concentration of which substance is different between the plasma and interstitial fluid? F. Calcium ions G. Chloride ions H. Potassium ions I. Proteins J. Sodium ions Osmosis 1 Definition: Osmosis is movement of water across a semi-permeable membrane from an area of low solute concentration to an area of high solute concentration Osmoles refers to the number of osmotically active particles in a solution In body fluids: osmolarity ≈ osmolality Osmolarity of body fluids maintained ~280 mOsm/L N.B. Texts often approximate this to 300 mOsm/L Image: Guyton & Hall Textbook of Medical Physiology Osmosis 2 ECF Sodium is the main osmotically active electrolyte ICF Potassium is the main osmotically active electrolyte Image: Guyton & Hall Textbook of Medical Physiology Osmotic Equilibrium Water can move easily between all compartments, so there is rapid equilibration between them when changes occur in one compartment Kidneys control volume and composition of plasma, which in turn can influence interstitial and intracellular fluids Can you explain the changes in volume and osmolarity that will be seen when solutions of different osmolarities are added to the ECF: A. Isotonic B. Hypotonic C. Hypertonic Image: Guyton & Hall Textbook of Medical Physiology Further Reading Guyton and Hall Textbook of Medical Physiology; 13th edition (Hall) Physiology; 6th edition (Costanzo) Medical Sciences; 2nd edition (Naish & Syndercombe Court) Netters Essential Histology; 2nd edition (Ovalle & Nahirney) Khan Academy introductory videos: https://www.khanacademy.org/science/health-a nd-medicine/human-anatomy-and-physiology/I ntroduction-to-the-kidneys/v/meet-the-kidneys Answers – Intro to the kidney 1 1. Name the four functions of the kidney. 1. Excretion of metabolic waste and toxins 2. Regulation of body fluid volume 3. Regulation of body fluid composition 4. Endocrine functions 2. Which part of the nephron tubule is closely associated with the juxtaglomerular apparatus? Distal convoluted tubule 3. What are the three components that form the filtration barrier in the renal corpuscle? 1. Glomerular capillary endothelium (fenestrated) 2. Basement membrane (negatively charged) 3. Epithelial cells (podocytes) Answers – Intro to the kidney 2 4. What type of epithelial cells line the proximal convoluted tubule? What specialised properties do these epithelial cells have? The proximal convoluted tubule is lined by simple cuboidal cells with microvilli (brush border) on the tubule side. These structures serve to increase the surface of the cell for solute exchange processes. The cells are also densely packed with mitochondria, indicating that the cells are highly metabolically active to generate energy for the transport of solutes 5. The loop of Henle has a major role in determining urine concentration by influencing the osmolarity of the medullary interstitium. Is the medullary interstitium hyposmolar, isoosmolar or hyperosmolar? The different properties of the thin descending limb, thin ascending limb and thick ascending limbs work together to generate a hyperosmolar interstitium in the medulla of the Answers – Body fluid composition The ICF constitutes about A. 40% total body weight B. 80% total body weight C. 20% total body weight D. 50% total body weight E. 10% total body weight Answer: A. 28 litres of ICF is present in a total body weight of 70kg The concentration of which substance is different between the plasma and interstitial fluid? F. Calcium ions G. Chloride ions H. Potassium ions I. Proteins J. Sodium ions Answer: D. Proteins. The capillary membrane is permeable to water and solutes, but impermeable to proteins