新疆医科大学 生理学教研室 Ch 9:Urinary physiology Wei yuanyuan Urinary physiology Urinary system Regulate the volume ,electrolytes composition,pH of internal enviroment homeostasis Urinary physiology ECF Simple marine organ ECF: sea-maintain constant Terrestrial animals ECF: kidney maintain water and electrolyte balance within very narrow range Urinary physiology Major Functions of the Kidneys Regulation of: body fluid osmolarity and volume electrolyte balance acid-base balance blood pressure Excretion of metabolic products foreign substances (pesticides, chemicals etc.) excess substance (water, etc) Major Functions of the Kidneys Secretion of erythropoietin 1,25-dihydroxy vitamin D3 renin prostaglandin Structure of kidney Gross Anatomy of the Kidney Structure of kidney Functional unit of kidneys ? Structure of kidney The nephron is the functional unit of the kidney: 1 million microscopic functional unit Perform almost all kidney’s functions Distinction between the cortical and medullary regions of the kidney Kidney -- nephron Renal cortex Renal pyramid nephron Renal medulla Renal pelvis Ureter Renal pyramid Structure of nephron Vascular component Afferent arteriole:no O2 and nutrients used Glomerulus: a tuft capillaries Efferent arteriole Peritubular capillaries:supply blood Tubular component Bowman’s capsule: cups around Proximal tubule:in cortex Loop of Henle Distal tubule and collecting duct Structure of Nephron Nephron Renal corpuscle Glomerulus Bowman’s capsule Renal tubular system Collecting duct Renal pelvis Fig 9- Structure of kidney Nephron Renal corpuscle Renal tubular system Proximal tubule Loop of Henle Distal tubule Collecting duct Renal pelvis Cortical nephron and Juxtamedullary nephron Regional differences in nephron structure Cortical nephron (80-90%) Glomuruli lie in the outer layer of the cortex Hairpin loop dips only slightly in the medulla Peritubular capillaries entwine around short loops of Henle Juxtamedullary nephron(10-20%) Glomeruli lie in the inner layer of the cortex Hairpin loop plunges entire depth of the medulla For establishment of the medullary vertical osmotic gradient Peritubular capillaries form vasa recta and run in closely with long loops of Henle The structure of nephron Cortical nephron or Juxtamedullary nephron ? Juxtaglomerular apparatus Juxtaglomerular apparatus Juxtaglomerular apparatus Granular cell(specialized vascular cells): secretion renin Macula densa(specialized tubular cells): sensing change in ECF volume↓/[NaCl] ↓/ blood pressure↓ Control renin release Mesangial cell Function as phagocytes Contraction : close off the filtration capillaris (sympathetic nerve excitation) Note: The distinction between juxtamedullary nephrons and juxtaglomerular apparatus Blood supply to kidney Blood supply to kidney Renal artery Segmental arteries Interlobar arteries Arcuate arteries Interlobular arteries Afferent arterioles Venous return of blood is via similarly named veins. Blood supply to kidney Blood supply to kidney Features of the renal blood flow: abundant blood flow 1200ml/min Two capillary beds High hydrostatic pressure in glomerular capillary (about 60 mm Hg)--filtration low hydrostatic pressure in peritubular capillaries (about 13 mm Hg)—reabsorption Vesa recta The efferent arterioles are the only arterioles in the body that drain from capillaries Urine formation Urine formation Basic three procedures Glomerular filtration Tubular reabsorption Tubular secretion Urine formation Afferent artery Efferent artery glomerular Glomerular filtration 20% of the plasma that enters the glomerulus is filtered. 2.75L Bowman’s capsule 180L/d Peritubular capillary Kidney tubule To venous system Urine excretion 80% of the plasma that enters the glomerulus is not filtered and leaves through the efferent arteriole Total plasma is 2.75L Urine formation Tubular reabsorption: selective movement of filtered substances from the tubular lumen into the peritubular capillaries 99% H2O and salts Active and passive mechanism Urine formation Tubular secretion selective transfer of nonfiltered substances from the peritubular capillaries into the tubular lumen Active transport Urine formation Urinary excretion refers to the elimination of substances from the body in the urine Urinary excretion rate(1.5L/d) Filtration rate(180L/d) -Reabsorption rate(178.5L/d) + Secretion rate Note: do not confuse excretion with secretion Glomerular filtration Urine formation Glomerular filtration Structure:glomerular membrane Force:effective filtration pressure Glomerular filtration Afferent arteriole Glomerular membrane Filtration fluid=proteins-free glomerulus blood plasma into Bowman’s capsule Bowman’s capsule Permeability is 100 times more than capillary elsewhere Filtration occurs through entire length of capillary Efferent arteriole Lumen of glomerular capillary Proximal tubule Glomerular filtration Layers of glomerular membrane (1)The wall of the glomerular capillaries (pore: more permeable) (2)Basement membrane (collagen and glycoproteins) (3)The inner layer of Bowman’s capsule Glomerular filtration (1)The endothelium of the capillaries pore: more permeable fenestrae 70-70nm prevent hemocyte from filtration negative charges: hinder plasma proteins hemocyte Glomerular filtration (2) Basement membrane Consists of a meshwork of collagen and glycoproteins Effectively prevents filtration of plasma proteins—strong negative electrical charges associated with the proteoglycans Capillary pore Glomerular filtration (3) The epithelial cells of Bowman’s capsule (podocytes) The foot processes are separated by gaps called slit pores (4-11nm) Provide additional restriction to filtration of plasma proteins.—negtive charges Glomerular filtration Permeability of filtration membrane Molecular size Large protein Albumin (albuminuria) Electrical charges of the molecule Negative charges Albumin (albuminuria) Glomerular filtration Effective filtration pressure, EFP (Net filtration pressure) Force favoring filtration Capillary blood pressure (BP:60mmHg) Bowman’s capsule colloid osmotic pressure (πB:0mmHg) Force opposing filtration Bowman’s capsule hydrostatic pressure (CP:18mmHg) Capillary colloid osmotic pressure (πC, COP: 32mmHg) Glomerular filtration Net filtration pressure (EFR) EFR=(BP+ πB) -(πC +CP) =BP-(πC +CP) = 60-(18+32)=10mmHg How does filtration stop? Increased glomerular capillary colloid osmotic pressure decreases GFR Filtration equilibrium Glomerular filtration Glomerular filtration rate (GFR) Definition 125ml/min(180L/day) Advantages of high GFR Glomerular filtrate produced by both kidneys per unit time Rapidly remove waste products Precisely and rapidly control of the volume and composition of the body fluid The fraction of plasma filtered by the glomerular capillaries 20% filtration fraction (FF)= GFR/ renal blood plasma flow Glomerular filtration Determinants of GFR: EFP (net filtration pressure) Kf : filtration coefficient the properties of the glomerular membrane How much glomerular surface area is available How permeability the glomerular membrane is GFR = Kf ×EFP Glomerular filtration Factors that affect the GFR Glomerular filtration 1 Favoring force-Capillary blood pressure (60mmHg) Depend on heart contraction (source of energy) BP ↓→GFR↓ <80mmHg Shock, hemorrhage, Glomerular filtration 2 opposing force-hydrostatic pressure in Bowman’s capsule:15mmHg↑→GFR↓ Urinary tract obstruction (stone) Precipitation of calcium or uric acid Prostatic enlargement Glomerular filtration 3 opposing force-Capillary colloid osmotic pressure (COP:30mmHg) ↑→GFR↓ Reduction in plasma protein concentration → COP ↓ →GFR↑ Lose a large quantity of protein-rich fluid through the exposed burned surface Glomerular filtration 4.Renal blood plasma flow blood plasma flow↑→ GFR↑ blood plasma flow↓ ↓→ Kf ↓→ GFR ↓ Glomerular filtration 5 Kf↓→ GFR↓ How much glomerular surface area is available How permeable the glomerular membrane is 4.2 ml/min/mm Hg per 100 grams of kidney weight (others capillary bed was only 0.01 ml/min/mm Hg per 100 grams ) Renal disease , Diabetes , Hypertension Regulation of renal blood flow Regulation of renal blood flow Auto-regulation nervous control Myogenic mechanism Tubulo-glomerular feedback Sympathetic nerve system Baroreceptor reflex Humoral control NE, E, Angiotensine Ⅱ, endothelin, bradykinin Regulation of renal blood flow Auto-regulation of renal circulation Mechanism BPA: 80-180 mm Hg Myogenic mechanism Tubulo-glomerular feedback Significance Preventing extreme changes in renal excretion Regulation of renal blood flow Myogenic mechanism BPA :80 mmHg--180 mmHg BPA↑→ constriction of afferent artery → the blood flow relatively less Contraction or relaxation in response to the stretch by blood pressure change Bp ↓ →vasodilation Bp↑→vasoconstriction Regulation of renal blood flow Tubulo-glomerular feedback BP ↓ →filtration ↓ →rate of fluid flow through tubules ↓ →macular densa(+)→Afferent arteriolar resistance↓ (mechanism remain elusive) →release AngⅡ ↑ → efferent arteriolar vasoconstriction →Glomerular hydrostatic pressure ↑ → filtration ↑ Regulation of renal blood flow Regulation of renal blood flow Neural regulation of renal blood flow Sympathetic nerve (+) →constriction of renal arteries (esp. afferent artery) → renal blood flow↓ Cause the mesangial cells to contract,close off a portion of the filtering capillaries. the para-sympathetic nerve does not exert any influence on the kidneys Regulation of renal blood flow Neural regulation of renal blood flow BPA↓ (hemorrhage)→ arterial carotid sinus and aortic arch baroreceptors (+) → BPA↑→renal blood flow remain constant Regulation of renal blood flow Humoral control Norepinephrine, epinephrine , endothelin Angiotensin Ⅱ Constriction of efferent arterioles Nitric Oxide Constriction of renal blood vessel (esp. afferent artery) and GFR↓ Renal blood vessels resistance ↓ Prostaglandins and bradykinin GFR↑