RENAL PHYSIOLOGY Listen to Audio Glomerulus Proximal renal tubule Loop of henle Distal renal tubule Collecting tubule GLOMERULUS -functions as filtration of blood creating an ultrafiltrate -Bowman’s capsule provides large surface area of capillary vessels -capillary vessels of Bowman’s capsule contains a single afferent and single effect arteriole -glomerular filtration pressure is inversely proportional to afferent arteriole tone -glomerular filtration pressure is directly proportional to efferent arteriole tone Glomerular Filtration Rate (GFR): normal GFR (in men) ≅ 120 +/- 25 ml /min, therefore: 95ml/min – 145ml/min normal GFR (in women) ≅ 95 +/- 20 ml/min, therefore : 75ml/min – 125 ml/min Renal Plasma Flow (RPF): RPF ≅ 660 ml/min Renal Blood Flow (RBF): RBF ≅ 20 – 25% CO = 1000 – 1250 ml/min Regulating factors affecting RBF may include: -Intrinsic Autoregulation -Tubuloglomerular Feedback -Hormonal Regulation -Neuronal Regulation Intrinsic Autoregulation -autoregulation of RBF generally occurs MAP between 80mmHg –180 mmHg -autoregulation may occur through myogenic responses creating vasodilation and vasoconstriction -myogenic vasodilation of glomerular afferent arteriole occurs as MAP falls close to 80mmHg -myogenic vasoconstriction of glomerular afferent arteriole occurs as MAP increases upto 180 mmHg -outside the range of 80 mmHg- 180mmHg MAP RBF becomes more pressure dependent ex. MAP < 70 mmHg: RBF generally decreases ex. MAP < 40 mmHg: RBF generally ceases Tubuloglomerular Feedback -renal tubular flow rates help maintain constant GFR with changing perfusion pressures via macula densa -macula densa located between the glomerulus and distal tubule making up the JGA ex. increased renal tubular flow rate sensed by macula densa decreases GFR decreased GFR accomplished by vasoconstriction of afferent glomerular arteriole ex. decreased renal tubular flow rate sensed by macula densa increases GFR increased GFR accomplished by vasodilation of afferent glomular arteriole and vasoconstriction of efferent Hormonal Regulation -RAAS helps to increase SVR and increased blood volume in order to ultimately increase MAP -increased MAP helps generate adequate perfusion pressure to establish proper glomerular filtration -vasodilating prostaglandins may include: PGD2, PGE2, PGI2 which may help in renal ischemia -ANP directly vasodilates renal arterioles and helps protect against constrictive actions of NE and Epi Neuronal Regulation sympathetic stimulation: T4 – L1 stimulate JGA via β1 and renal arterioles via α1 -results in decreased RBF ex. stress-induced decrease in renal blood flow PROXIMAL RENAL TUBULE -major function is Na+ reabsorption of the ultrafiltrate formed from the glomerulus -nearly 75% of the ultrafiltrate formed from the glomerulus is reabsorbed by the proximal tubule -reabsorption of Na+ requires ATP via ATPase exchanging Na+/K+ ion pumps reabsorption of Na+ allows for -reabsorption of other solutes (ex. Ca2+, Mg2+, K+) -secretion of H+ (important for acid/base regulation) -absorption of H20 Factors which may increase Na+/K+ exchange via ion pumps include: -angiotensin II -norepinephrine Factors which may decrease Na+/K+ exchange via ion pumps include: -dopamine via D1 receptors Proximal tubules allow for secretion of cations: ex. creatinine -cimetidine -quinidine Proximal tubules allow for secretion of anions: ex. urate -ketoacids -penicillins -cephalosporins -diuretics -salicylates -contrast dyes LOOP OF HENLE -main function is to maintain a hypertonic interstitium within the renal medulla -purpose of hypertonic renal medulla interstitium allows the collecting tubule to concentrate urine -countercurrent multiplier mechanism maintains the hypertonic interstitium ≅ 75% of the ultrafiltrate is reabsorbed by the proximal tubule therefore only ≅ 25% reaches the loop ≅ 15 – 20 % of the original Na+ load from the glomerulus is reabsorbed by the Loop of Henle -site of action of loop diuretics (ex. furosemide) Loop of Henle permeability to water -descending limb of loop of Henle: permeable to water -thin ascending limb of loop of Henle: permeable to water -thick ascending limb of loop of Henle: impermeable to water *results in hypotonic tubular fluid exiting loop of Henle (100 – 200 mOsm/L) *results in hypertonic interstitial renal medulla DISTAL RENAL TUBULUE -major site for the action of PTH and vitamin D mediated reabsorption of Ca2+ -PTH helps increase Ca2+ absorption secretion of phosphate -receives hypotonic tubular fluid from the loop of Henle and modifies fluid to minor extent -DCT involved with ≅ 5 % of Na+ reabsorption before delivering the tubular fluid to the collecting tubule -site of action for thiazide diuretics (ex. HCTZ) COLLECTING TUBULE can be anatomically and functionally divided into: -cortical collecting tubules: site of action of aldosterone -medullary collecting tubules: site of action ADH Cortical Collecting Renal Tubule consist of two cell types: -principal cell (P-cell): secretes K+ and reabsorbs Na+ with aldosterone influence -intercalated cell (I-cell): involved with acid-base regulation Aldosterone affects the cortical collecting renal tubule via: -stimulation of Na+/K+ ATPase -increased number of K+ channels within the luminal membrane -increased number of Na+ channels within the luminal membrane Intercalated cells (I-cells) may regulate acid/base balance via: -luminal K+/H+ ATPase pump which reabsorbs K+ and secretes H+ -secretion of H+ provides renal compensation amidst acidosis Medullary Collecting Renal Tubule: -principal site of action of ADH -ADH stimulates V2 receptors which activates adenylate cyclase creating cAMP -stimulation of V2 increases expression of aquaporin 2 which allows permeability of water -water leaves medullary collecting tubule and travels to the hypertonic medullary interstitium *results in water conservation and inhibits diuresis ex. during dehydration: stimulates ADH and promotes water conservation (inhibits diuresis) ex. during adequate hydration: decreased ADH release and promotes urine formation