Urinary P.pptx PDF

PHAS5001 Anatomy & Physiology Physiology of the Urinary System Delivered by Prof Fahad Rizvi MRCS, MRCGP Thank you to Nisha Valand for the slide deck and Dr Louise Dunford for some of...

PHAS5001 Anatomy & Physiology Physiology of the Urinary System Delivered by Prof Fahad Rizvi MRCS, MRCGP Thank you to Nisha Valand for the slide deck and Dr Louise Dunford for some of the information in these slides  Learning Outcomes To Describe:  The main functions of the kidney  How urine is formed via glomerular filtration, tubular reabsorption and secretion  How the medullary osmotic gradient is maintained  How urine concentration and volume is regulated  The Urinary System Kidneys and the structures that carry urine from the kidneys to the outside of the body Kidneys Ureter Bladder Urethra  Kidneys 2 x bean-shaped kidneys ~ 150 g each; 11 x 6 x 3 cm 250,000 – 2,000,000 nephrons per kidney Process ~ 180 L fluid per day Kidney Functions Homeostasis Ions pH Osmolality Blood pressure Gluconeogenesis – production of glucose Hormones Erythropoietin Renin Prostaglandins Vitamin D  Kidney: Urine Formation Step 1: Glomerular Filtration Step 2: Tubular Reabsorption Step 3: Tubular Secretion ©Pearson Education International Step 1: Glomerular Filtration Podocyte ©Pearson Education International  Step1:1:Glomerular Step GlomerularFiltration Filtration Three layers of the filtration membrane: 1. Fenestrations of glomerular capillaries 2. Basement membrane 3. Foot processes of podocytes  Step1:1:Glomerular Step GlomerularFiltration Filtration Molecules < 3 nm in diameter > 5 nm generally don’t pass pass freely from the blood to through the barrier the glomerular capsule E.g. water, glucose, amino acids, nitrogenous waste E.g. blood cells & proteins  Step 1: Glomerular Filtration Glomerular filtration rate (GFR) Volume of filtrate formed each minute Normal GFR = 120 – 125 ml/min Important clinically as it’s a indicator of how well kidneys are working GFR depends upon: Net filtration pressure Surface area available for filtration Filtration membrane permeability  Step 1: Glomerular Filtration Hydrostatic pressure forces fluids and solutes through filtration membrane Net filtration pressure is 10 mmHg HPgc = hydrostatic pressure of glomerular capilliary ©Pearson Education OPgc = osmotic pressure of glomerular capillary International HPcs = hydrostatic pressure of capsular space  Step 1: Glomerular Filtration Step 1: Glomerular Filtration GFR is tightly regulated – why? To make filtrate To maintain To maintain blood extracellular pressure homeostasis Intrinsic controls (renal autoregulation): directly control GFR Extrinsic controls (nervous and endocrine systems): indirectly control GFR  Step1:1:Glomerular Step GlomerularFiltration Filtration Intrinsic controls (renal 2. Tubuloglomerular feedback autoregulation) mechanism Kidneys can maintain nearly constant GFR through adjusting resistance to blood flow, despite changes in systemic blood pressure 1. Myogenic feedback mechanism:  Step1:1:Glomerular Step GlomerularFiltration Filtration Extrinsic controls (nervous and endocrine Systemic blood systems) pressure  Purpose of extrinsic controls is to regulate GFR to help maintain the Sympathetic fibres systemic blood pressure release norepinephrine 1. Sympathetic nervous system Baroreceptor reflex controls: Afferent arterioles Neural renal controls serve the constrict & decrease needs of the body as a whole (e.g. GFR Helps restore blood in emergency situations such as volume and BP hypovolemic shock)  Step1:1:Glomerular Step GlomerularFiltration Filtration Extrinsic controls (nervous and endocrine Systemic blood systems) pressure  Purpose of extrinsic controls is to Renin released regulate GFR to help maintain the systemic blood pressure Angiotensin II 2. Renin-angiotensin-aldosterone Aldosterone Vasoconstricti mechanism: on of Increase Na + systemic Body’s main mechanism for absorption & water arterioles increasing BP Increases blood Low BP causes renin to be released volume Systemic blood by granular cells of the afferent pressure  Decrease in systemic blood pressure  Step 2: Tubular Reabsorption Kidneys filter ~180 L per day Urine is ~ 1.5 L per day Tubular reabsorption reclaims most of the content of the filtrate Process begins as soon as the filtrate reaches the proximal tubules Selective transepithelial ©Pearson Education process International  Step Step 2: 2: Tubular Tubular Reabsorption Reabsorption Transcellular route 1. Transport across apical membrane 2. Diffusion through cytosol 3. Transport across basolateral membrane 4. Movement through interstitial fluid into the capillary Paracellular route Movement through leaky tight junctions ©Pearson Education International Through interstitial fluid  Step Step 2: 2: Tubular Tubular Reabsorption Reabsorption m al i x ute Na+ r o P v ol n co ubule dt Glucose, amino acids, vitamins Cl-, K+, Mg2+, Ca2+, other ions Most active area of HCO3- the tubule. Absorbs: Water All glucose and amino acids in Lipid-soluble solutes the filtrate ©Pearson Education International 65% of Na+ &  Step Step 2: 2: Tubular Tubular Reabsorption Reabsorption Descending limb Water Ascending limb Na+, Cl-, K+ Difference in Mg2+, Ca2+ permeability to water in the descending Loop of Henle and ascending limbs plays a vital role in ©Pearson Education International ability to concentrate  Step Step 2: 2: Tubular Tubular Reabsorption Reabsorption Distal convoluted tubule Na+, Cl-, duct Collecting Na+, Cl- K+ Ca2+ HCO3- Water Reabsorption in this area is fine-tuned by Urea hormones: Antidiuretic hormone ©Pearson Education International  Step Step 2: 2: Tubular Tubular Reabsorption Reabsorption Antidiuretic Aldosterone hormone (ADH) Fine-tunes absorption of Inhibits diuresis Na+ (urine output)  blood pressure or Makes cells of volume or  K+ cause the collecting duct more adrenal gland to release permeable to water aldosterone Therefore more Increases Na+ water is reabsorbed reabsorption  Step Step3: 3:Tubular TubularSecretion Secretion Tubular secretion = reabsorption in reverse Removes substances from the peritubular capillaries into the filtrate Also transfers substances that are made in peritubular cells, e.g. HCO3- Therefore urine contains both filtered and secreted substances ©Pearson Education International  Step Step3: 3:Tubular TubularSecretion Secretion Tubular secretion is important for: Drugs and some metabolites which Plasm a Drug are tightly bound to plasma protei n proteins Eliminating end products that have been reabsorbed by passive processes, e.g. urea, uric acid  Step Step3: 3:Tubular TubularSecretion Secretion Tubular secretion is important for: Getting rid of excess K+ Nearly all K+ is reabsorbed in the PCT Aldosterone leads to secretion in the DCT and collecting ducts Controlling blood pH When pH becomes acidic, tubule cells secrete more H+ into the filtrate and generate more HCO3- pH rises and more H+ is excreted in the urine  Kidney: Urine Formation Step 1: Glomerular Filtration Step 2: Tubular Reabsorption Step 3: Tubular Secretion ©Pearson Education International https://www.youtube.com/watch? v=iKusxCtH62c Regulation of urine concentration & volume Intake and loss of fluids varies hour-to-hour Hot day vs. cold day Activity levels Amount of drinks Kidneys make adjustments to keep solute concentration of body fluids ~300mOsm Regulate urine concentration and volume to achieve this Countercurrent mechanism  Regulation of urine concentration & volume Countercurrent mechanisms 1. Countercurrent multiplier Interaction between the flow of the filtrate in the descending and ascending limbs of the Loop of Henle 2. Countercurrent exchanger Flow of blood between the ascending and descending portions of the vasa recta  Regulation of urine concentration & Countercurrent multiplier volume 30 The two limbs are close 0 Osmolality of interstitial fluid enough to influence each 40 other’s exchanges with the 0 interstitial fluid 60 The more NaCl that leaves the 0 ascending limb the more water 90 Urea (mOsm) leaves the descending limb 0 Urea The ascending limb uses the 120 increasingly concentrated 0 filtrate in the descending limb Regulation of urine concentration & volume Countercurrent exchanger Vasa recta Helps preserve the medullary gradient Prevents rapid removal of salts from the interstitial space Removes reabsorbed water  Regulation of urine concentration & Kidneys use urea to help form the volume medullary gradient Urea enters the filtrate in the ascending limb via diffusion As the filtrate enters the collecting duct water is usually reabsorbed, leaving the urea behind When the urea reaches the end of the URE collecting duct lowest in the medulla it A moves out into the interstitial fluid The urea then recycles back into the ascending limb Regulation of urine concentration & volume Why do we need the medullary osmotic gradient? Without the gradient urine could not have a concentration over 300 mOsm Without being able to have urine >300 mOsm we would not be able to conserve water when dehydrated  Regulation of urine concentration & volume Overhydrated osmolality of ECF ADH release H2O reabsorption from collecting duct Large volume of dilute urine  Regulation of urine concentration & volume Dehydrated  osmolality of ECF  ADH release  H2O reabsorption from collecting duct Small volume of concentrated urine  Diuretics  Diuretics are drugs that enhance urinary output  Used for high blood pressure or when body is retaining too much fluid  Most work by inhibiting sodium-associated transporters  Three main types:  Loop diuretics, e.g. furosemide, act on the ascending limb to inhibit formation of the medullary gradient  Thiazide diuretics, e.g. bendroflumethiazide, act at the DCT Many different renal Renal disease diseases Usually lead to damage to the glomerulus, capillaries, tubules, or interstitum (or combination of more than one) Consequences are: Reduction in the ability of the kidney to filter the blood Leakage of proteins into Bladder diseases Cancer – ccc Infection – cystisis Stones Sphinctor incontinence - muscle becomes weaker -> cannot hold in urine Hyperactive bladder – urine frequency increases – treatment: Bladder botox: Toxins damage->kill nerve endings so nerves stop working; muscle stop working….Sulphonesine for bladder control Urethra diseases PUV Discharge – infection (STI) Narrower urethra -> caused by injury: post infection, post surgery Hypospadias  Ureters Two slender tubes that transport urine from the kidneys to the bladder Incoming urine distends the ureter and muscles contract to propel it to the bladder Peristaltic waves adjust according to the amount of urine formed Renal calculi (kidney stones) Crystalisation of calcium, magnesium or uric acid salts in the renal pelvis Can get stuck in the ureter and block urine drainage  Urinary bladder Function = storage of urine Holds ~500 ml urine, but can stretch to hold about double that if necessary Micturition (urination) = emptying the bladder Three things need to happen simultaneously: Contraction of detrusor Internal urethral sphincter opens Incontinence: Weakened pelvic muscles External urethral sphincter opens Urinary retention: after anaesthetic, detrusor muscle takes time to regain activity; hypertrophy of prostate gland  Urethra Thin walled tube that carries urine out of the body Internal urethral sphincter is involuntary and controlled by the autonomic nervous system External urethral sphincter is voluntarily controlled Length of urethra is 3 – 4 cm in females Cystitis: & 20 cmcommon in malesin women due to short length of urethra and proximity to anal opening  Resources Marieb, Elaine N.;Hoehn, Katja N.. 2015., Human Anatomy & Physiology, Global Edition. Pearson Education Limited. Tortora, G.J. and Derrickson, B. (2014). Principles of Anatomy and Physiology. 14th ed. Hoboken, NJ: Wiley Series of videos about renal physiology: https://www.khanacademy.org/science/health-and-medicine/human-a natomy-and-physiology/introduction-to-the-kidneys/v/how-do-our-kid neys-work Some simple practice questions: https://www.khanacademy.org/test-prep/mcat/organ-systems/the-ren al-system/e/renal-system-questions  Learning Outcomes To Describe:  The main functions of the kidney  How urine is formed via glomerular filtration, tubular reabsorption and secretion  How the medullary osmotic gradient is maintained  How urine concentration and volume is regulated