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Responding to ill Health Life Science The Urinary System Madhero88 (2009) https://commons.wikimedia.org/wiki/File:FullUSys_copy.png 1 Learning Outcomes • Identify the body fluid compartments, and describe the gross and microscopic structure of the kidney • Outline the multiple roles of the urinary system in maintaining homeostasis • Explain urine production related to nephron structure and the processes of filtration, selective reabsorption and tubular secretion. • Explain the hormonal regulation of urine composition and volume, and the homeostatic role of the kidney in producing renin and erythropoeitin 2 Functions of Kidney • Excretion of nitrogenous waste (breakdown of proteins) • Regulation of blood pH (acidity/alkalinity) • Regulation of electrolyte balance (salts) • Regulation of blood volume and blood pressure • Production of hormones – Calcitriol – vit. D – maintains calcium levels – Erythropoietin – red blood cell production – Homeostasis! 3 Relevance • Renal Disease indicates range of renal function e.g. • • • • • • • fluid problems e.g. oedema waste accumulation e.g. uraemia electrolyte imbalance e.g. hyperkalaemia acid/base imbalance e.g. acidosis hypertension e.g. blood volume, renin anaemia e.g. lack of erythropoietin musculoskeletal e.g. gout 4 Kidney Function – Elimination of waste – Nitrogen from protein breakdown • Amino acids contain Nitrogen atom which is removed (Deamination) in liver, creating Ammonia (NH3) - highly toxic • The liver further converts Ammonia to Urea • Urea is much less toxic than Ammonia, but must still be excreted • Liver Disease – can’t convert the toxic ammonia to urea – encephalopathy • Kidney Disease – urea can be made but kidneys can’t excrete - uraemia • Both conditions may be fatal 5 Other nitrogenous waste • Breakdown of Nucleic acids e.g. DNA forms waste product URIC ACID Hellerhoff (201) https://commons.wikimedia.org/wiki/File:Gichtfuss_im_Roentgenbild_002.png • Excess uric acid in blood causes gout • Crystals of uric acid in joints – very painful! Arnaudus (2004) https://commons.wikimedia.org/wiki/File:AcideUrique.png 6 Bobjgalindo (2005) https://commons.wikimedia.org/wiki/File:Fluorescent_uric_acid.JPG 2. Tubular selective reabsorption Madhero88 (2010) Physiology of Nephron https://commons.wikimedia.org/wiki/File:Physiology_of_Nephron.png Urine formation – 3 key processes 1. Glomerular filtration 7 Madhero88 (2010) Physiology of Nephron https://commons.wikimedia.org/wiki/File:Physiology_of_Nephron.png Urine formation 1. Glomerular filtration 8 Glomerulus Blood : • arrives at glomerulus via afferent arteriole • exits glomerulus via efferent arteriole • Each kidney receives 1200ml blood/min • 25% of cardiac output • Renal blood flow kept at constant pressure (independent of systolic pressure) • Controlled by juxtaglomerular apparatus (part of DCT) OpenStax College (2013) https://commons.wikimedia.org/wiki/File:Juxtaglomerular_Apparatus_and_Glomerulus.jpg?uselang=en-gb Glomerular Filtration • Pressure in glomerular capillaries is 55mmHg • Body capillaries usually 25mmHg • Glomerular capillaries covered in special connective tissue – Capsular epithelium – prevents bursting NET filtration pressure =55-(15+30) = 10 mmHg 3. Blood colloid osmotic pressure = 30 mmHg 2. Capsular hydrostatic pressure = 15 mmHg 1. Glomerular capillary pressure = 55 mmHg 10 Henry Gray (1918) Gray1130 https://commons.wikimedia.org/wiki/File:Gray1130.svg + UWS Staff (2015) Filter Layers of wall of capillaries • Podocyte cells of capsular epithelium – interlocking mesh • Cells and plasma proteins too big to filter - stay in blood • Damage to capsular epithelium – wider holes - protein passes through Proteinuria OpenStax College (2013) https://commons.wikimedia.org/wiki/File:2613_Podocytes.jpg?uselang=en-gb 11 Glomerular filtration Na+ glucose proteins BOWMAN’S CAPSULE filtrate ClH 2O H 2O Na+ Cl- N.B Concentration of Glucose and Sodium Chloride is the same in filtrate as plasma but not plasma proteins. glucose •Glomerular damage – Nephrotic syndrome • Proteinuria (protein in urine) • Plasma protein ↓ • Fluid movement: blood → tissue - Oedema • e.g. Pre-eclampsia – hypertension during pregnancy James Heilman, MD (2010) https://commons.wikimedia.org/wiki/File:Combinpedal.jpg UWS Staff (2015) GLOMERULUS Blood cells blood Plasma Glomerular filtration rate (GFR) • Each kidney receives 1200ml blood/min • Glomerular filtration rate – amount of filtrate formed per minute ~120ml/min • But ~119ml/min reabsorbed leaving 1ml/min of urine = 60ml/hour = 1440ml/day • GFR can be measured to assess kidney function • Patient drinking normally – 60ml urine/hour • Less than 30ml/hour = kidneys not functioning properly 13 Glomerular Filtration • If GFR = 120ml/min then would mean 180 litres formed per day (but we only have 5L of blood!) • Must reabsorb the majority or we’d die from hypovolaemic shock in minutes • Reabsorption occurs in tubules of nephron • Filtrate returned to blood in peritubular capillaries Burton Radons (2012) https://commons.wikimedia.org/wiki/File:Nephron_illustration.svg?uselang=en-gb 2. Tubular selective reabsorption Madhero88 (2010) Physiology of Nephron https://commons.wikimedia.org/wiki/File:Physiology_of_Nephron.png Urine formation 15 Reabsorption • Active or passive • Passive - depends on concentration/or pressure gradients • Osmosis (water movement) important – Plasma osmotic pressure is higher than the filtrate – due to plasma proteins • Active transport systems use energy Selective tubular reabsorption • Reabsorption of important filtrate components into blood (via peritubular capillaries) • Mainly in proximal convoluted tubule (PCT) • As plasma moves along peritubular capillaries [glucose] and [sodium] gets higher – (so [water] is lower) • Water follows by osmosis from PCT to peritubular capillaries 17 Selective Reabsorption • • • • Sodium is filtered yet most of it reabsorbed Requires energy So why filter it?? Homeostasis requires precise control of sodium levels • In deficiency, reabsorb more • If in excess, reabsorb less Selective Reabsorbtion Glucose & amino acids • normally completely reabsorbed (none in urine) Sodium & chloride • reabsorbed - both active & passive transport Diabetes mellitus • Excess blood glucose • Too much glucose filtered - can’t all be reabsorbed – Glycosuria • Less water is reabsorbed as a result – dilute urine Reabsorption • Substances not reabsorbed in the PCT now move into the Loop of Henle • Further 20% water and salt are reabsorbed here • High [Solute] concentration in medulla - helps osmosis from collecting ducts (to concentrate urine) OpenStax (2013) https://commons.wikimedia.org/wiki/File:2621_Loop_of_Henle_Countercurrent_Multiplier_System.jpg?uselang=en-gb Urine formation 3. Tubular secretion • Active process Madhero88 (2010) Physiology of Nephron https://commons.wikimedia.org/wiki/File:Physiology_of_Nephron.png • Opposite direction to reabsorption • Substances not required by body secreted in urine • Drug secretion (e.g. penicillin, aspirin) • Hydrogen ion secretion, removes excess acid from body (controls blood pH) 21 Tubular Secretion • Blood pH range 7.35 - 7.5 • Blood pH ↓ - then H+ ions secreted from plasma • Bicarbonate (buffer) ions reabsorbed into plasma • Urine pH indicates health of DCT • If plasma pH low, urine pH even lower (H+ secretion) Kidney disease • Plasma pH falls below 7.35 - acidosis • Patient may be acidotic but urine pH normal as DCT not secreting Summary - TUBULAR PROCESSES Glomerular filtration : (plasma minus plasma proteins PCT : Fixed reabsoption Glucose Amino Acids 65% of Sodium Chloride Water DCT : Controlled reabsorption of sodium by ALDOSTERONE LOOP OF HENLE : Fixed reabsorption 20% Sodium Chloride Water NOTE THAT FIXED REABSORPTION HAPPENS AUTOMATICALLY ! CONTROLLED REABSORPTION OCCURS THROUGH HORMONAL EFFECTS ! Burton Radons (2012) https://commons.wikimedia.org/wiki/File:Nephron_illustration.svg?uselang=en-gb COLLECTING DUCT : Controlled reabsorption of water by – ADH Hormonal control of reabsorption • Fluid passes from loop of Henle into the Distal Convoluted Tubule (DCT) • DCT is site of final reabsorption of Na+ • Regulated by Aldosterone secreted by adrenal glands Burton Radons (2012) https://commons.wikimedia.org/wiki/File:Nephron_illustration.svg?uselang=en-gb Hormonal control Aldosterone – increased reabsorption of sodium and water – increased potassium secretion into urine – Ion exchange – Result: ↑ Blood pressure (BP) – Aldosterone production regulated by kidneys – Low BP, Na+ or blood volume → kidney secretes enzyme RENIN (enzyme) – Initiates Renin-Angiotensin System (RAS) 25 EEOC (2006) https://commons.wikimedia.org/wiki/File:Illu_adrenal_gland.jpg Renin Angiotensin System Angiotensin II powerful vasoconstrictor (↑ BP) also stimulates adrenal cortex to produce aldosterone Aldosterone ↑ Na+ reabsorption in DCT 26 UWS Staff (2015) Final stage of urine formation • Collecting duct (CD) receives the filtrate from DCT • CD moves through the renal medulla toward renal pelvis • Final reabsorption of water occurs • Under hormonal control from Antidiuretic Hormone (ADH) Burton Radons (2012) https://commons.wikimedia.org/wiki/File:Nephron_illustration.svg?uselang=en-gb ADH concentrates urine • High blood osmotic pressure ADH secretion • ↑ permeability of walls of DCT & collecting ducts (channels opened) • ↑ osmosis & water reabsorption • Urine becomes more concentrated Diabetes insipidus • Insufficient ADH • Collecting ducts less porous • Large volume of dilute urine produced 28 ADH • If you drink too much (overhydrate) • levels of ADH drop • less water is reabsorbed from CD • large volume DILUTE urine produced • If drink too little (dehydrated) • high ADH levels • maximal reabsorption water from CD • CONCENTRATED urine The Kidneys and Hypertension • Hypertension can be due to – Excess ADH causing increased blood volume – Excess Aldosterone causing Na+ retention • Hypertension is both an effect of renal disease and a cause of renal disease • Patients with kidney disease – Malignant Hypertension (Hypertensive Emergency) – CNS, CVS, kidneys impaired – May be irreversible damage • Stimulates production of red blood cells from bone marrow • Low oxygen levels → kidneys release EPO (altitude training) • ‘Doping’ in sport Calcitriol • Hormonal form of vitamin D • Aids calcium absorption in GIT • ↑ tubular reabsorption of calcium from glomerular filtrate (prevents excretion) de:Benutzer:Hase (2002) https://commons.wikimedia.org/wiki/File:Lance_Armstrong_MidiLibre_2002.jpg Erythropoietin (EPO) Erik van Leeuwen (2013) https://commons.wikimedia.org/wiki/File:Mo_Farah_(2)_Moscow_2013.jpg?uselang=en-gb) Hormones released by kidney: 31 WATER AND ELECTROLYTE BALANCE Electrolytes • salts & ions dissolved in water • Osmotic pressure of body fluids • Essential roles in physiology UWS Staff (2015) Biezl (2008) https://commons.wikimedia.org/wiki/File:Gibbs-donnan-en.svg Water Balance • Need to avoid dehydration/overhydration – Usual intake 2500ml/day • Causes of dehydration : – – – – – Poor intake Sweating Diarrhoea Diuretics Diabetes Water Gain Water Loss Metabolism (200 ml) Food (700 ml) Drinking (1600 ml) Faeces (100 ml) Exhaled (300 ml) Evaporation from skin (600 ml) Urine (1500 ml) • Overhydration can be caused by UWS Staff (2015) – Excessive intake – Insufficient excretion from kidneys (kidney failure or excess ADH) • Acute renal failure patients usually need restricted fluid intake Electrolyte Balance Sodium • Na+ is major (+) ion in extracellular fluid (ECF) and essential for nerve and muscle function • Excess salt removed by kidneys (↓ aldosterone) • XS sodium retention → water retention to maintain osmotic pressures → increases ECF and plasma volume → increased blood pressure Potassium • K+ major intracellular ion (ICF) (ECF levels are low) • Essential for normal nerve and muscle function • Changes in K+ harmful to the heart (lethal injection – potassium chloride) Electrolyte Balance - calcium • • • • Ca2+ abundant in dairy and fish Absorption in GIT is inefficient - Vit D aids this Most stored in bone but some in ECF and ICF Parathyroid hormone major controller • Ca2+ roles: – – – – Muscle contraction Blood clotting Activation of complement immunity Nerve and muscle (including cardiac) function Hypocalcaemia • ↑ excitability of nerve /muscle → muscle spasms Hypercalcaemia • muscle weakness • Kidney stones • Bone softening