Introduction To The Kidney PDF

Introduction to the kidney Course Renal system Lecturer Prof David Henshall Overview Functions of the kidney Body fluid composition The nephron Simple overview of urine formation The kidney is a key organ in homeostasis Kidney structure Bean shaped organs located on e...

Introduction to the kidney Course Renal system Lecturer Prof David Henshall Overview Functions of the kidney Body fluid composition The nephron Simple overview of urine formation The kidney is a key organ in homeostasis Kidney structure Bean shaped organs located on either side of the spine under the ribcage Filter blood removing waste and water to make urine. Urine travels down the ureter and gets stored the bladder  Kidney structure Kidneys: Bilateral retroperitoneal organs Blood supply: Renal artery and vein Filtrate forms in Bowman’s capsule in the Cortex Urine flows from collecting ducts into calyces.  Primary function of the kidneys 1. Regulate the volume and composition of the extracellular fluid (ECF). Kidneys regulate volume and composition of the plasma which then results in regulation of volume and composition of the entire ECF 2. Eliminate potentially toxic metabolic wastes and foreign compounds  Functions of the kidneys cont. Maintain water balance in body Maintaining proper plasma volume Regulation of blood pressure Maintain osmolarity (solute concentration) of body fluids primarily by regulating water balance  Functions of the kidneys cont. Regulating quantity and concentration of extracellular fluid ions Na+, K+, Cl-, Ca2+, PO43- Maintaining acid-base balance pH  Functions of the kidneys cont. Excreting waste products of metabolism – Urea (from metabolism of amino acids) – Uric acid (from metabolism of nucleic acids) Excreting foreign compounds – Drugs, food additives Other –Converting vitamin D to active form (by proximal tubule cells) Regulation of Ca /bone 2+ – Producing erythropoietin (cells in interstitium of cortex/outer medulla) Hormone stimulates red blood cell production  Renal control of body fluid composition Water accounts for 60% of body mass 2/3 is intracellular, 1/3 extracellular Extracellular fluid is the fluid outside cells It consists of: The plasma which surrounds the blood cells The interstitial fluid which surrounds the cells of all other tissues There is free exchange of water and solutes, except proteins, between plasma and interstitial fluid (across capillary walls) Distribution of fluid depends on hydrostatic and osmotic forces Intracellular fluid Changes in composition will affect cell physiology! Body fluid composition  Determinants of plasma and ECF osmolarity Plasma osmolarity determined mainly by NaCl content relative to the water content of the blood (salt accounts for major ionic/osmotic content of plasma) A decrease in water content, by increasing the NaCl concentration, increases osmolarity An increase in water content, by lowering the NaCl concentration, lowers osmolarity Kidneys maintain water balance in order to maintain plasma/ECF 1 mmol free ions = 1 mosmol osmolarity constant The osmolarity of plasma and ECF is normally maintained constant at 283 ± 11 mosmol/l. This in turn maintains the osmolarity of cell fluid Qu: Is there a tendency for the content of the ECF (and therefore the blood), to change? Food contains salts and water → continuing tendency for levels of salt and water to rise Exercise (sweating) Other causes: vomiting, diarrhoea… Kidneys offset this effect by excreting salt and water in amounts appropriate to intake  Functional unit of the kidney - nephron The nephron is the functional unit of the kidney. Approx. 1 - 1.2 million nephrons in each kidney. Each nephron consists of two parts. Two sub-parts of the nephron The renal corpuscle tuft of capillaries (glomerulus) Bowman’s capsule Tubular system fluid filled tube formed by single layer of epithelial cells Vascular supply Nephron structure – more detail  Tubular components of the nephron and their functions Bowman’s Capsule – collects glomerular filtrate Proximal Convoluted Tubule (PCT) – absorption and secretion of selected substances occurs here Loop of Henle – establishes an osmotic gradient in the renal medulla (ascending and descending loops have different channels/functions) Distal Convoluted Tubule (DCT) – controlled reabsorption of Na+ and water, secretion of K+ and H+ Collecting Duct – takes fluid (urine) into the renal pelvis What is the functional unit of the kidney? a. Glomerulus b. Bowman’s capsule c. Nephron d. Collecting duct Basic processes performed by the nephron 1) Filtration of blood 2) Tubular reabsorption 3) Tubular secretion  Simple overview of urine formation Filtration of blood to form Salt and water Reabsorption of content of filtrate tubular filtrate most of the adjusted to match (mainly salt & filtrate back intake water) into blood Blood leaving in Efferent arteriole Blood entering in afferent arteriole Secretion from blood, of certain substances, into filtrate  Renal blood flow (RBF) and blood supply to nephron First process in nephron is ultrafiltration of the plasma in the glomerulus. This step is dependent on generation of strong hydrostatic pressure in nephron Kidney requires abundant blood supply Blood supply to the two kidneys is via the renal arteries Blood flow to the kidneys is ~1.2 L/min. very high: 1/5 of cardiac output* *normalized for tissue weight this is 7 fold higher than the brain!  Blood supply of the nephron Renal artery subdivides to form many afferent arterioles which each supply a nephron Glomerular capillaries recombine to leave Bowmans Capsule as efferent arterioles. Efferent arterioles give rise to peritubular capillaries which invest the tubular system of each nephron. These then recombine to form venules and the renal vein Function of Peritubular Capillaries 1. Nutritive 2. Reabsorptive 3. Secretive  1. Glomerular filtration Plasma from the blood entering glomerulus is filtered out (~20%) into Bowman’s capsule Filtrate then flows through tubular system where substances of value are reabsorbed to peritubular plasma What passes through the filtration barrier to form the tubular filtrate? All components of plasma, except cells and proteins, pass (a small amount of protein does pass but is immediately reabsorbed – a normal sample of urine should have no protein). So, useful substances as well as waste pass through Volume of tubular filtrate formed Approx. 180 litres of filtrate forms per day - entire ECF “treated” ~10 times per day Approx. 1.5 litres of urine are excreted Therefore, approx. 178.5 litres of filtrate must be reabsorbed (returned to the blood) per day 2. Tubular reabsorption Tubular reabsorption is tremendous, highly selective & variable Tubules have high reabsorptive capacity for substances needed Little/no reabsorptive capacity for useless/harmful substances (which stay in filtrate) 99 % filtered is subsequently reabsorbed 99% of H20, 100% glucose, 99.5% salt  Tubular reabsorption Can be active (energy requiring) or passive Active: one or more steps in transepithelial transport requires energy (ATP) expenditure Active: glucose, amino acids, Na+ Movement during one or more steps against a gradient Passive: water, chloride ion occurs down electrochemical or osmotic gradient Tubular reabsorption involves transepithelial transport Steps of trans-epithelial transport 1) Substance leaves tubular fluid 2) Passes through cytosol of tubular cell 3) Crosses basolateral membrane 4) Diffuses through interstitial space 5) Penetrates capillary wall to enter blood plasma Tubular epithelial cell Capillary wall Peri-tubular capillary Basolateral membrane Tubular lumen *Tight junctions between tubular cells prevent substances moving in-between cells → materials must pass through cells plasma Interstitial fluid  Example: Na+ reabsorption* Tubule cell Tubular lumen diffusion Na+ diffusion K+ ATP Na+ K+ plasma Interstitial fluid *dealt with in full in a later lecture  Reabsorption is substance and location specific Proximal tubule Na+ 67% H20 65% Loop of Henle Na+ 25% H20 15% Distal tubule and collecting tubules Na+ 8% H20 20% 3. Tubular secretion Also involves transepithelial transport Transfer of substances from peritubular capillaries into tubular lumen H+, potassium, organic ions Drugs, food additives environmental pollutants Urine excreted Urine is final “product” of nephron’s work. Approx. 1ml/min formed Comprises: H20 Urea (formed in liver as end product of protein metabolism) Creatinine (waste product of muscles) Ions (Na+, K+) Phenol Slightly acidic (pH approx. 6.0) Osmolarity varies according to water levels (from 50 – 1200 mOsm) Learning outcomes Explain the main functions of the kidneys. Describe the basic tubular and vascular system of the nephron. Explain the three major processes performed by the nephron to produce urine. Describe body fluid composition. Define the normal volume and composition of urine.  Reading suggestions “Medical Sciences” by Niash (Ch 14) “Human Physiology” by Sherwood (Ch 14, 15) https://www.youtube.com/watch?v=FN3MFhYPWWo