Lecture Presentation Urinary system

The Urinary System : The Urinary System


Organs : Organs Kidneys Functional components of urinary system Partially protected by 11th - 12th pairs of ribs Right kidney slightly lower ureters urinary bladder urethra


Functions : Functions Functions of the kidneys include: Regulating blood ionic composition Na+, K+, Ca2+, Cl-, HPO42- Regulating blood pH Excrete variable amounts of H+ and conserve and produce bicarbonate Regulating blood volume Conserve and eliminate variable amounts of water in urine Regulating blood pressure Via regulation of blood volume as well as vasoconstrictive effects of ADH Maintaining blood osmolarity (no. of dissolves particles per litre of solution) Separately regulates loss of water and solutes Producing hormones Calcitriol – active form of vitamin D EPO – stimulates production of erythrocytes Regulating blood glucose level Carries out gluconeogenesis Excreting wastes and foreign substances


Kidney anatomy : Kidney anatomy Renal capsule protection maintains kidney shape Adipose capsule protection holds kidney in place Nephroptosis may occur in very thin people Renal fascia anchors to surrounding structures and abdominal wall


Kidney : Kidney Renal Hilus ureters, blood vessels, lymphatic vessels and nerves enter and exit kidney Structure: Cortex Medulla columns Extension of cortex providing route for nerves and blood vessels pyramids Papillary ducts run into apex (papilla) Minor and major calyces Renal pelvis


Nerve and blood supply of kidney : Nerve and blood supply of kidney Kidneys receive 20-25% of resting cardiac output Each nephron receives an afferent arteriole Divides into ball shaped capillary network called glomerulus Glomerular capillaries reunite to form efferent arteriole Carries blood out of glomerulus Vasa recta and peritubular capillaries extend from some efferent arterioles Supply blood to tubular portions of nephron Renal nerves part of sympathetic division of ANS Most are vasomotor nerves that regulate blood flow through kidney


Nephron : Nephron Nephron functional unit of the kidney Consists of: Renal corpuscle Glomerulus Bowman’s capsule Renal tubule proximal convoluted tubule loop of Henle distal convoluted tubule


Nephron : Nephron Two classifications of nephron: Cortical (80-85%) glomerulus in outer cortex short loop of Henle penetrates to outer medulla Juxtamedullary (15-20%) glomerulus deep in cortex long loop of Henle Ascending limb has two portions Thin ascending limb Thick ascending limb Penetrates deep into medulla Establish high osmolarity in renal medulla


Nephron : Nephron Nephron performs 3 functions: glomerular filtration Water and most solutes in blood plasma move across glomerular capillaries into capsular space then into renal tubule tubular reabsorption Tubule cells reabsorb ~99% of filtered water and useful solutes tubular secretion Tubule and duct cells secrete wastes, drugs, excess ions into fluid


Glomerular filtration : Glomerular filtration Endothelial cells of glomerular capillaries encircled by podocytes Pedicels of podocytes form filtration slits Filtration membrane Permits filtration of water and small solutes but not blood cells, platelets or most plasma proteins Mesangial cells Located among glomerular capillaries Regulate diameter of capillaries


Glomerular filtration : Glomerular filtration Net filtration pressure depends on glomerular blood hydrostatic pressure capsular hydrostatic pressure blood colloid osmotic pressure


Clinical note : Clinical note In some kidney diseases glomerular capillaries are damaged Plasma proteins enter glomerular filtrate Reduces blood coloid osmotic pressure More fluid moves into tissues Causes edema


Glomerular filtration rate : Glomerular filtration rate Glomerular Filtration Rate (GFR) Volume of filtrate formed in all renal corpuscles of both kidneys each minute Averages 125 ml/min If GFR too high substances pass too quickly through tubules for adequate reabsorption Excess urinary loss If GFR too low Nearly all filtrate reabsorbed Certain wastes may not be adequately excreted GFR remains relatively constant due to: Adjustments in glomerular blood flow Alteration of glomerular capillary surface area available for filtration Mesangial cells regulate this


Glomerular filtration rate : Glomerular filtration rate GFR controlled by: Renal autoregulation Neural regulation Hormonal regulation


Renal autoregulation of GFR : Renal autoregulation of GFR Renal autoregulation of GFR Two mechanisms Myogenic Stretching triggers contraction of smooth muscle cells in wall of afferent arterioles Glomerular blood flow reduces GFR reduces Normalises GFR within seconds after a change in blood pressure Tubuloglomerular feedback Macula densa provides feedback to regulate diameter of afferent arteriole via the juxtaglomerular apparatus


Juxtaglomerular apparatus : Juxtaglomerular apparatus Final part of ascending limb of LOH makes contact with afferent arteriole Tubule cells in this region of LOH crowded together macula densa detect changes in delivery of Na+, Cl- and H20 Wall of afferent arteriole contains modified smooth muscle cells Juxtaglomerular cells release nitric oxide which adjusts diameter of afferent arteriole Macula Densa and Juxtaglomerular cells together make Juxtaglomerular apparatus


Tubuloglomerular regulation of GFR : Tubuloglomerular regulation of GFR When GFR high less time for reabsorption of Na+, Cl- and H20 macula densa detects increased delivery of Na+, Cl- and H20. NO release by juxtaglomerular cells inhibited Afferent arteriole constricts Decreases blood flow through afferent arteriole and decreases GFR


Neural regulation of GFR : Neural regulation of GFR Blood vessels in kidneys supplied by sympathetic ANS fibres Stimulation (such as during exercise etc) causes constriction of afferent arteriole Reduces GFR Reduces urine output so as to conserve blood volume Permits greater blood flow to other tissues


Hormonal regulation of GFR : Hormonal regulation of GFR ANP Released by atria when stretched (high blood volume / high BP) Causes relaxation of glomerular mesangial cells Increases capillary surface area for filtration GFR increases Angiotensin II Vasoconstrictor formed in response to low blood pressure Causes constriction of afferent (and efferent arterioles) Reduces GFR Increases reabsorption to increase BP


Tubular reabsorption : Tubular reabsorption Normal rate of GFR (~125 ml/min) means that the volume of fluid entering the PCT in ½ hour is greater than total plasma volume Normally ~99% of filtered water and solute reabsorbed PCT makes major contribution to reabsorption More distal tubules fine tune reabsorption to maintain water and ion balance Solute reabsorption drives water reabsorption because all water reabsorption occurs via osmosis Obligatory water reabsorption Water reabsorbed with solutes (water ‘obliged’ to follow solutes) Occurs in PCT and descending LOH – always permeable to H2O Facultative water reabsorption Ability of water to follow solute dependent on availability of ADH Occurs mainly in collecting ducts


Reabsorption and secretion - PCT : Reabsorption and secretion - PCT Largest amount of solute and water reabsorption occurs in PCT Most absorptive processes involve Na+ Filtered glucose, amino acids, lactic acid, vitamins and other nutrients reabsorbed by Na+ symporters Na+ also reabsorbed by Na+/H+ antiporters Can provide mechanism for reducing blood H+ PCT cells can produce own H+ to keep antiporter running to ensure adequate Na+ reabsoprtion H+ produced by carbonic anhydrase reaction HCO3- produced from carbonic anhydrase reaction reabsorbed NH4+ can substitute for H+ Produced by deamination of glutamine Also produces HCO3- which is reabsorbed Reabsorption of solutes promotes water reabsorption via osmosis (obligatory water reabsorption)


Reabsorption – Loop of Henle : Reabsorption – Loop of Henle Reabsorption of water via osmosis not automatically coupled to reabsorption of solutes Descending LOH permeable to water, relatively impermeable to solutes Water reabsorbed via osmosis Ascending limb of LOH permeable to solutes, relatively impermeable to water Solutes reabsorbed via Na+-K+-2Cl- symporters


Reabsorption – DCT : Reabsorption – DCT Reabsorption of Na+ and Cl- via Na+-Cl- symporters Relatively impermeable to water Does not follow via obligatory water reabsorption Major target for parathyroid hormone stimulated increase in Ca2+ reabsorption


Reabsorption and secretion – collecting ducts : Reabsorption and secretion – collecting ducts By time filtrate reaches end of DCT 90-95% of filtered solutes and water have been reabsorbed Collecting ducts relatively impermeable to water Water reabsorption under facultative control


Hormonal regulation of tubular reabsorption and secretion : Hormonal regulation of tubular reabsorption and secretion Most important regulators of tubular electrolyte reabsorption and secretion are Angiotensin II Aldosterone Major hormone regulating tubular water reabsorption is ADH


Renin – angiotensin – aldosterone system : Renin – angiotensin – aldosterone system When BP and BV low walls of afferent arteriole stretched less Reduced stretch causes juxtaglomerular cells to release renin Renin also released in response to sympathetic stimulation Renin clips off 10 amino acid peptide called angiotensin I from angiotensinogen (plasma protein) Angiotensin I converted to angiotensin II (active) in lungs by ACE (angiotensin converting enzyme) clipping off another 2 amino acids Angiotensin II constricts afferent arterioles reduces GFR and allows more time for reabsorption stimulates Na+, Cl-, and water reabsorption in PCT stimulates aldosterone secretion by adrenal cortex increases reabsorption of Na+, Cl- and H20 in collecting ducts Also stimulates thirst centre in hypothalamus


Antidiuretic hormone : Antidiuretic hormone ADH released by posterior pituitary Secretion regulated by negative feedback Hypothalamic osmoreceptors regulate secretion of ADH in response to changes in blood osmolarity ADH regulates facultative water reabsorption in last part of DCT and collecting ducts Stimulates insertion of water channel (aquaporin-2) into apical membranes of principal cells


Urine production : Urine production Homeostasis of body fluid volume depends in large part on the ability of the kidneys to regulate the rate of water loss in urine ADH controls whether dilute or concentrated urine is formed


Producing dilute urine : Producing dilute urine Descending limb of LOH permeable to water impermeable to solutes Water moves out solutes cannot follow Ascending limb and collecting ducts permeable to solutes (active transport) Contribute to medullary osmotic gradient impermeable to water (dependent on ADH) Solutes actively transported out but water cannot follow


Producing concentrated urine : Producing concentrated urine Production of concentrated urine is dependent on a high osmotic gradient in the renal medulla High osmotic gradient established by juxtamedullary nephrons: Thick ascending limb cells of LOH reabsorb ions from filtrate and pass into medulla Urea recycling Urea recycled from distal tubule to medulla and equilibrates with LOH Maintains medullary osmolarity Sluggish flow of blood in vasa recta allows equilibrium with medullary osmolarity ie blood does not remove solutes and destroy gradient


Producing concentrated urine : Producing concentrated urine ADH increases insertion of aquaporin-2 in collecting ducts When filtrate passes through high osmolarity of deep renal medulla water moves according to osmotic gradient Results in concentrated urine


Clinical note - diuretics : Clinical note - diuretics Diuretics slow renal reabsorption of water Most act by blocking Na+ transporters Less Na+ reabsorbed Less water reabsorbed by obligatory reabsorption Cause diuresis (increased urine production) Reduces plasma volume Reduces edema


Urine transport, storage and elimination : Urine transport, storage and elimination Urine drains from collecting ducts into calyces, renal pelvis and then ureters Stored in urinary bladder Average capacity 700-800 ml Sensation of fullness initiates conscious desire to urinate before bladder ½ full Once bladder approx ½ full stretch receptors in bladder wall transmit afferent nerve impulses to micturition centre in sacral spinal cord Efferent impulses cause contraction of detrusor muscle (lines wall of bladder) and relaxation of internal urethral sphincter muscle Micturition can be delayed through conscious contraction of external urethral sphincter (skeletal muscle)


Aging and the urinary system : Aging and the urinary system Kidneys shrink in size Reduced blood flow Filter less blood Sensation of thirst diminishes with age Increased dehydration Urinary dysfunction more prevalent Polyuria – excessive urine production Nocturia – excessive urination at night Dysuria – painful urination Incontinence hematuria