1995b(5): Outline the effected of 500ml of IV 20% mannitol, and the potential problems associated with its use General: Mannitol is an osmotic diuretic 20% solution = 200mg/ml Osmolality = 1100 mosm/l Uses: CSF pressure/volume Peri-operative diuresis in jaundiced Pts (renoprotective) Initiate diuresis in transplanted kidneys Physicochemical: Low-MW compound (182Da) Freely filtered at glomerulus, nil absorption Doesn t cross BBB (charged polysaccharide) 4 x plasma osmolality MOA: osmolality of ECF osm glomerular filtrate urine vol Problems with use: ECF osmolality - depletion of ICF - activation of central osmoreceptors ADH from post pituitary (only need 1-2% change to activate) plasma vol - stretch low pressure baroreceptors (great vessels, RA) ANP further Na +, H 2 O loss o 10% volume change needed for activation of system - risk CCF in susceptible individuals Uncontrolled diuresis - Dehydration o osmolality of tubular filtrate o ANP o ICF/ECF vol depletion Electrolyte abnormalities - ANP Na + depletion - ATII/Aldosterone Na + depletion - Aldosterone K + reabsorption hyperkalaemia
1996a(7): In the diagram below indicate how the solvent and solute move across the semi-permeable membrane. Briefly explain the principles BLOOD Potassium (6.5 mmol.l -1 ) Urea (40 mmol.l -1 ) Osmolality (320 mosmol.l -1 ) Pressure (100 mmhg) SEMIPERMEABLE MEMBRANE DIALYSATE Potassium (3.5 mmol.l -1 ) Urea (0 mmol.l -1 ) Osmolality (346 mosmol.l -1 ) Solvent: H 2 O (medium for solute transfer) Solute: K +, Urea. Both dissolved in H 2 O Pressure (10 mmhg) Semi-permeable membrane allows the passive diffusion of solute & solvent down gradients Concentration gradient i.e movement of the solute down its concentration gradient - In general, net movement of solutes (K, urea) down their electrochemical gradients from blood dialysate - Obey s Fick s Law of Diffusion Flux = A x sol (C B C D ) where A=surface area of membrane, T=thick T MW sol= solubility, MW=mol wt, C B -C D = conc gradient b/n blood, dialysate - Therefore, flux affected by: o A, T o Flow would transfer across the semi-permeable membrane - [K] B would approach [K] D (~3.5mmol/L) - [urea] B would also approach [urea] D (0mmol/L) Osmotic gradient i.e. movement of solutes down osmotic gradient - Solvent (H 2 O) moves from low osm high osm - Osmotic gradient = (blood dialysate) = 320 346 = -26mosm/L - Therefore, favours movement of water from blood to dialysate Pressure gradient i.e. diffusion of H 2 O across semi-permeable membrane based on hydrostatic pressure solvent drag ie flow of solvent will drag solute - Starling hypothesis Flux H 2 O = K f [(P B P D ) σ(π B π D )] = K f [90 σ(20 0)] Therefore, net movement of H 2 O from blood dialysate
1998b(3): Describe the process of tuboglomerular feedback General: Tuboglomerular feedback relates the reflex arc by which the macula densa influences afferent arteriolar tone in order to ensure constant tubular fluid flow through the nephron. Collectively, both form the JGA Macula Densa - Located within the wall of the ascending Loop of Henle/early DCT - Close to the renal arterioles - Controls tone of afferent arteriole via release of vasoactive substances o Adenosine (vasoconstrictor) via α 1 receptor activation o NO (vasodilator) - Release of vasoactive substances determined by Na + content of tubular fluid in ascloh renal perfusion pressure glomerular capillary pressure GFR Na + (& Cl - )content of fluid in ascloh Na + /Cl - detected by macula densa Na/K ATPase activity adenosine release Constriction of afferent arteriole glomerular cap pressure GFR renal perfusion P (MAP) glomerular capillary P GFR Na + /Cl - content in ascloh Na + /Cl - detected by MD Na/K ATPase activity adenosine /? NO release Dilate afferent arteriole glomerular capillary P GFR
2000b(8)/1998a(5): Describe the factors governing GFR General: GFR = glomerular filtration rate = 125ml/min (180l/day) = comprised of plasma ultrafiltrate (large proteins remain in plasma) Filtration occurs within the renal corpuscle, comprised of - Bowman s capsule - Network of capillaries invaginating the capsule o Supplied by afferent arteriole o Drained by efferent arteriole GFR - Based on balance of Starling s forces o Glomerular capillary hydrostatic pressure (P G ) o Bowman s capsule hydrostatic pressure (P B ) o Glomerular capillary oncotic pressure (π G ) Such that net filtration pressure (NFP) NFP(mmHg) = P G P B π G Degree of filtration is dependent on factors such as surface area and membrane permeability dependent on the filtration coefficient (K f ) such that GFR = K f.nfp NFP is higher at afferent end of renal corpuscle - P G NFP afferent = 60 15 21 = 24mmHg Lower at efferent end - P G - π G NFP efferent = 58 15 33 = 10mmHg 1. Effect of afferent/efferent arteriolar tone on GFR Afferent tone - tone P G NFP GFR o Adenosine (TGF), ATII, Adrenaline - tone P G NFP GFR o ANP, NO, PG Efferent tone - Moderate tone P G NFP GFR o ANP - Severe tone GFR o Adrenaline, ATII - tone P G NFP GFR a) Tuboglomerular feedback. - Part of autoregulation. MD senses Na, Cl in DCT activity Na/K ATPase adenosine production constriction afferent arteriole GFR
b) MAP - Autoregulation by local vasoactive substances (adenosine, NO), and myogenic mechanism and TGF maintain GFR across MAP 75 175mmHg c) k f = Capillary hydraulic permeability x surface area - k f : ATII, SNS d) Plasma oncotic pressure - plasma oncotic pressure will favour net filtration GFR. o Liver disease e) reflection coefficient - Reflection coefficient normally omitted from Starling equation as is 1 in normal nephron. - Protein losing nephropathy will reflection coefficient, meaning that it is leaky to protein will further plasma oncotic pressure and interstitial oncotic pressure (normally 0) GFR
2001a(1): Outline the determinants and regulation of ECF vol General: ECF is sum of intravascular and interstitial fluid compartments - 20% body weight (~14L 70kg ); 1/3 total body water Determinants of ECF vol - H 2 O able to move freely b/n ICF and ECF - Movement maintains osmotic equilibrium b/n compartments o ECF osm = ICF osm - Normal osmolality 280-295mosm/l - ECF osmotically active solute = Na + (Cl - ) Na 1 determinant ECF vol - IV volume detectors (high/low pressure baroreceptors) will only be activated after >10% IV vol loss (>4L TBW) 2 H 2 O flux from ICF ECF Regulation of ECF Vol 1. ADH (nonapeptide) - Hypothalamic osmoreceptors detect 1-2% change in osmolality - osmolality inhibition post pituitary release ADH Renal effect: - Bind V 2 receptors CD camp insert aquaporins in membrane facilitate H 2 O reabsorption - ADH-urea transporters urea reabsorption from tubular fluid into renal medullary interstitium osmotic gradient b/n tubular fluid and medulla Result: H 2 O reabsorption and formation of small vol concentrated urine (max osm 1400mosm/kg H 2 O) Negative Feedback: - Return to normal osm negative feedback on post pituitary ADH release - <280mosm/L essentially nil ADH release 2. RAA system - Na + ECF ECF vol - stretch afferent arteriole stretch intrarenal baroreceptors release renin from granular cells JGA - Renin cleaves angiotensinogen ATI, ATI Lungs (ACE) ATII/ATIII adrenals aldosterone release Effect: - ATII: Constrict eff>aff arteriole (slight GFR, also part of autoregulation), Na + H 2 O reabsorp n CD - Stimulate ADH release - Central effect: Stimulate hypothalamic thirst centre Result: input in order to correct deficit - Aldosterone: Na + H 2 O reabsorp n CD small vol conc urine Negative feedback: ATII negative feedback on renin release 3. ANP - intravascular vol stretch RA release ANP - Dilation afferent arteriole / constriction efferent arteriole Effect: GFR water, solute filtered. However, Na absorption is proportional to GFR, therefore reabsorption Na glomerulotubular balance
2003a(16): Describe the functions of the Loop of Henle, including the physiological mechanisms involved General: Loop of Henle (LoH) is portion of nephron between PCT and DCT that is responsible for creating the interstitial osmotic gradient in the renal medulla which is necessary for formation of concentrated urine Position: - Cortical nephrons have short LoH o Thin ascending limb passively moves Na out of tubular fluid (Low Na in interstitium, osmotic gradient 50% contribution of urea) - Juxtamedullary nephrons (15%) have long LoH which extend into renal medulla o Thick ascending limb actively pumps Na/Cl/K out of tubular fluid Function: - osmotic gradient within the interstitium - formation of concentrated urine (1400mosm/kg) in the presence of ADH Mechanism of Action: Counter-Current Multiplier Descending and ascending limbs closely oppose each other, parallel AcsLoH (thick) actively pumps out Na/Cl (co-transport) into interstitium osm interstitium, osm tubular fluid Tubular fluid passes from PCT descloh As moves into medulla, osm interstitium DescLoH permeable to H 2 O (impermeable to Na + /Cl - ) H 2 O exits lumen Tubular osm = medullary osm at base of LoH (max 1400mosm) AscLoH is impermeable to H 2 O Active transport of Na + /K + /Cl - out of tubule into interstitium osmolarity of tubular fluid High interstitial osm Presence of ADH aquaporin insertion collecting ducts movement of H 2 O out (2 osmotic gradient) Concentrated urine Role of Urea - 50% Urea passively absorbed into interstitium from PCT - Still present in tubular fluid [urea] in collecting duct fluid - In presence of ADH, ADH-urea transporter in CD absorption of urea (& H 2 O) from CD interstitium (contributes 50% of osmotic pull) NB Nil ADH [urea] interstitium concentrating ability of LoH
2003b(14)/1999b(4): Outline the role of the kidney in the regulation of body water General: Kidneys are the primary method by which body water is regulated - Receives 25% (1250ml/min) resting CO o Produces high volumes of ultrafiltrate Body Water Regulation - Important in homeostasis o Optimal size/vol body fluid compartments o Compartment osmolarity - Water balance: Input = Output Filtration: Blood is filtered through renal corpuscle to form ultrafiltrate o GFR ~180L/day Reabsorption: - Reabsorption of H 2 O & electrolytes is determined by pressure, osmolarity via direct effects and hormone release Tuboglomerular Feedback (part of autoregulation) - Intra-renal osmoreceptors (macula densa) o renal perfusion pressure GFR tubular fluid osmolarity (via Na/Cl) detected by MD adenosine constrict afferent arteriole o renal perfusion pressure GFR tubular osmolarity detected by MD NO release dilate afferent arteriole - Maintains GFR constant MAP 75 175mmHg in combination with myogenic mechanism. Myogenic Mechanism - stretch afferent arteriole: via myogenic mechanism stretch reflex contraction of afferent smooth mm o Autoregulates filtration pressures over wide MAP Pressure: - MAP o Stretch atria release of ANP afferent tone/ efferent tone GFR Diuresis Inhibition RAA system/adh o Detected by central baroreceptors ADH from post pituitary ADH-urea transporters in CD / aquaporin insertion CD renal medullary osmolarity (urea reabsorption) diuresis - MAP o stretch central/peripheral (RA, great vv) baroreceptors 10% ECF vol loss ADH post pituitary ( rapidly beyond 10% loss) MOA: binds V 2 receptors in CD camp opens aquaporins ADH-urea transporters urea reabsorption into medullary interstitium
renal medullary osmolarity concentrating ability of kidney H 2 O reabsorption o afferent arteriolar pressure detected by intrarenal baroreceptors Stimulate renin release granular cells JGA cleaves angiotensinogen ATI ACE (lungs) ATII Aldosterone release from adrenal cortex GFR Na + /H 2 O reabsorption from CD SVR - stretch high P baroreceptors (carotid sinus/aortic arch) o Removal inhibition SNS CO, SVR Renin release (β 1 stimulation) Constrict afferent/efferent arterioles (α 1 stimulation) GFR Osmolarity - Central osmoreceptors o osmolarity (<280mosm) of vascular compartment (excess H 2 O) ADH from post pituitary H 2 O reabsorption large vol dilute urine o osm (>300mosm) ADH H 2 O reabsorption small vol conc urine Obligatory Urine Loss - Solute load of 600mosm/day must be excreted o Urea, sulphates, phosphates, metabolic by-products) - Min urine loss of 430ml to accommodate this o As max concentrating capacity of urine = 1400mosm/kg H 2 O)
2004a(13)/1998b(1): Describe the concept of renal clearance and its use to estimate GFR Definitions: Renal Clearance GFR = volume of plasma cleared of a substance per unit time = ml/min (L/day) - All of substance removed from plasma ends up in the urine CL = UV where CL=clearance, U=urine conc of substance, P V=urinary vol, P=plasma conc = rate of filtration of blood at the glomerulus - 2 balance of Starling s forces in glomerular capillaries = 125ml/min (180L/day) - The rate of removal of a tracer substance (clearance) from glomerular plasma flow is used to estimate GFR Amount of tracer filtered (P t ) Amount of tracer in urine (U t ) = Plasma conc(p) x GFR = Urine conc(u) x Urine vol(v) P t = U t P x GFR = UV GFR = UV P GFR = CL t - Ideal tracer (Inulin): infusion rate = excretion rate = UV [P] steady state [P] steady state P o Non-toxic o Easy to administer IV o Freely filtered at the glomerulus o Not actively secreted/absorbed/metabolised/synthesised by tubules o Not affect the functioning of the kidney (no physiological reactance) - Creatinine is a by-product of muscle breakdown, is a physiological tracer appropriate for estimating GFR as it has most of above o Has some active secretion in PCT (not reabsorbed) o CL Creatinine > GFR (over-estimates)
2004a(16)/2001b(6)/1999a(4): Explain how the kidney handles glucose. Describe the consequences of glycosuria Kidney handling of Glucose - Glucose is freely filtered at the glomerulus - In early PCT, secondary active transport (co-transport) occurs with Na + and facilitated diffusion o Na + moved from tubular cell into peritubular capillary via Na/K ATPase at basolateral membrane o Tubular Na + moves down concentration gradient into tubular cell provides energy for transport of glucose across luminal membrane SGLT-1 in PCT luminal membrane - Glucose then transferred from cell to interstitial fluid via GLUT-2 transporter peritubular capillaries - Essentially all glucose is normally reabsorbed with only minute amounts appearing in urine Renal Threshold - Glucose transport system is a saturable process I.e. changes from 1 st order zero order kinetics o T max = 300-375mg/min filtered glucose load ( ) Filtered load < T max complete reabsorption Filtered load > T max glycosuria o At normal GFR (125ml/min) threshold is at plasma glucose 10-12mmol/L 1.88mmol/min filtered glucose load o But predicted threshold is 16mmol/L - Actual threshold < predicted 2 splay o heterogeneity in glucose reabsorption mechanisms b/n nephrons o Maximal enzyme activity occurs only after filtered glucose load > T max Consequences of glycosuria - Osmotic diuresis o Glucose has high osmotic pull within tubule limits H 2 O absorption in ascending LoH by conc gradient o Medullary dilution impaired concentrating ability of nephron o H 2 O reabsorption via aquaporins in DCT - vol urine extracellular volume depletion (dehydration) o K + reabsorption as is proportional to tubular fluid flow (now high) o Na + reabsorption 2 extracellular vol Electrolyte depletion - circulating glucose ketone production / catabolic processes - risk infection o substrate in urine o impaired immune system (2 high plasma glucose)
2004b(12)/2002b(13): Briefly describe the secretion and function of renin and angiotensin General: Kidney plays a role in the regulation of body water and electrolytes - Important part of this is the juxtaglomerular apparatus (JGA) JGA Consists of 2 parts which are adjacent to each other - JG cells in the wall of the afferent arteriole o Involved in pressure regulation through production of adenosine o Pressure detection: afferent arteriolar baroreceptors o Effector mechanism: Production of renin (granular cells) - Macula densa in the wall of the distal tubule o 1 role in tubuloglomerular feedback (autoregulation) through Sensor for fluid flow in DCT Production of locally active vasoconstrictor Release of renin controlled by: - intra-renal baroreceptors (stretch) 2 MAP, extracellular fluid vol - SNS (via β 1 stimulation of JG cells) - Macula densa via detection of Na + / K + content in tubular fluid through LoH/DCT (tuboglomerular feedback) - ATII (negative feedback) Production and release of renin (enzyme) Renin cleaves angiotensinogen (liver produced) ATI -lungs (1 source of ACE) cleaves ATI ATII (cleaved to ATIII (less potent)) adrenal cortex aldosterone production Function of Renin - Rate limiting enzyme required for the activation of the RAA system Function of Angiotensin GFR - Constricts afferent and efferent arterioles (afferent<efferent) - K f (filtration coefficient) Tubular Absorption - Direct effect on tubules to Na + reabsorption - Indirect effect via production of aldosterone Na + /H 2 O reabsorption, K + excretion from collecting ducts Vasoconstrictor - Peripherally vasoconstricts MAP - Constricts peritubular capillaries capillary pressure fluid reabsorption SNS Stimulation - Via peripheral and central mechanisms o CO, MAP Central effect - Stimulation of thirst centre water intake - Stimulation of hypothalamus ADH release Negative feedback on renin production
2005a(11)/2001a(7): Describe how the body detects and responds to a water deficit General: H 2 O deficit ECF osmolality (relative Na + ). Systemic detection causes 1 in H 2 O reabsorption in the kidney to maintain homeostasis Detection Systems 1. Osmoreceptors (Normal: 280-295mosm/L) - Most sensitive detector o Detects 1-2% change ECF osm stimulates response - Na + in ECF (with H 2 O deficit) osmolality detected by central osmoreceptors (hypothalamus) ADH release from post pituitary Effect - ADH: nonapeptide produced in hypothalamus, stored in post pituitary - Release triggered by osmoreceptors activation - Kidney: V 1 R activation DCT camp aquaporin insertion DCT/CD permeability to H 2 O - Kidney: urea transporter activity absorption urea into medullay interstitium osmolality osmotic gradient to H 2 O reabsorption - Vasculature: V 2 R activation camp Ca vasoconstriction SVR (afterload) maintain MAP Negative Feedback - H 2 O reabsorption osmolality activity of osmoreceptors ADH release - <285mosm/L nil ADH release When water deficit uncorrected activation of other detector systems 2. Volume Detection Systems - Low pressure baroreceptors (Volureceptors) (great vessels, RA) Detects ~10% change in vol intravascular (>4L total body water depletion) o stretch inhibition of post pituitary further ADH release - High pressure baroreceptors (carotid sinus / aortic arch) MAP (10-15% ECF vol) o stretch activation of SNS, RAA system - Intrarenal baroreceptors o MAP renal perfusion pressure stim n renin release o Tuboglomerular feedback part of autoregulation. P (intra-renal baror) NO production macula densa maintain GFR 75-175mmHg (unable to maintain beyond limits) Effector Systems 1. SNS - Constriction of afferent/efferent arteriole (α 1 receptors) o renal perfusion pressure GFR - Stimulation of granular cells JGA (β 1 receptors) o renin release - Central stimulation of thirst centre (hypothalamus) intake - Peripheral vasoconstriction to maintain MAP 2. Renin-Angiotensin System
- Renin (enzyme) released from JGA 2 SNS stim n, intrarenal pressure - Cleaves angiotensinogen ATI, ATI to lungs (ACE) ATII, ATII to adrenals aldosterone - Effect: o Central: stimulation of thirst centre input to correct deficit o ATII (ATIII less potent) SVR, Na + /H 2 O reabsorption CD, Constriction of efferent>afferent arteriole to maintain GFR o Aldosterone Na + /H 2 O reabsorption CD
2005b(10): Describe the forces acting across the glomerular capillary membrane. Explain how afferent and efferent arteriolar tone affect GFR General: Kidneys receive 25% resting CO (1250ml/min) - Functional unit of kidney is nephron (~1million per kidney) - Protein-free plasma ultrafiltrate is formed within the renal corpuscle, which then passes through the rest of the nephron o Renal corpuscle = network of glomerular capillaries invaginating Bowman s capsule - Nephron is supplied by afferent arteriole, blood exits the renal corpuscle via efferent arteriole Glomerular Filtration - Starling s forces within the renal corpuscle result in the net filtration of protein free fluid (ultrafiltrate) into Bowman s capsule o Glomerular capillary hydrostatic pressure (P G ) o Bowman s capsule hydrostatic pressure (P B ) o Glomerular capillary oncotic pressure (π G ) Net filtration pressure (NFP) = P G P B π G - Also dependent on capillary surface area, membrane permeability o Known as filtration coefficient (K f ) Glomerular filtration = K f x NFP - NFP at afferent end of capillary > NFP at efferent end o 2 P G, π G Afferent = P G (60) P B (15) - π G (21) = 24mmHg Efferent = P G (58) P B (15) - π G (33) = 10mmHg Afferent / Efferent Arteriolar Tone - Changes will effect glomerular filtration via changes to NFP - Major effect with changes to afferent arteriolar tone (effect of o tone blood flow P G NFP GFR Eg ATII tone afferent/efferent arterioles o tone blood flow P G NFP GFR Eg Prostaglandins, eicosanoids - Efferent tone o Moderate tone efferent flow P G NFP GFR Eg ANP afferent tone / efferent tone o Extreme tone GFR overall Tubuloglomerular feedback - Part of renal autoregulation maintains GFR b/n MAP 70-170mmHg - GFR Na load detected by macula densa adenosine production afferent arteriolar tone GFR to that nephron Glomerulotubular balance - Na/Cl reabsorption not fixed proportionate to GFR - GFR Na/Cl reabsorption to maintain balance
2006a(14)/2002a(6)/1995b(2): Explain the physiological process which cause oliguria in response to hypovolaemic shock General: Hypovolaemic shock is a state whereby the body is unable to meet the metabolic demands of tissue (delivering O 2, substrates / removing wastes) due to inadequate intravascular (circulating) volume. 1 depletion in H 2 O & Na. Characterised by: - tendency for VR CO - MAP - Depending on the cause of hypovolaemic shock ECF osmolality may be isoosmolar (haemorrhage) or hyperosmolar (dehydration) Compensatory Mechanism: Oliguria (<0.5ml/kg/hr (<25ml/hr) urine production) Aim of Oliguria: Retain H 2 O, Na + Detection Systems Osmoreceptors (Normal: 280-295mosm/L) - Most sensitive detector (1-2% change osmolality) activation compensation High pressure baroreceptors (aortic arch, carotid sinus): - 10-15% depletion intravascular vol (>4L TBW depletion) - SNS inhibition o RAA activation o GFR o Maintain MAP Low pressure baroreceptors volureceptors (great vessels, RA): - ~10% intravascular depletion - inhibition posterior pituitary ADH release Intra-renal baroreceptors - MAP renal perfusion pressure GFR - renin release JGA RAA activation Macula Densa (JGA) tuboglomerular feedback - Na/Cl content tubular fluid MD release NO dilate afferent arteriole maintain GFR o MAP <70mmHg autoregulation fails (myogenic mechanism / tuboglomerular feedback cannot maintain constant GFR) Effector Mechanisms ADH - Nonapeptide produced in post pituitary after stimulation by hypothalamus - Effects: o Vascular: bind V 1 receptors vascular smooth muscle constriction o Renal: bind V 2 receptors CD camp inserts aquaporins CD o Renal: ADH-urea transporters urea reabsorption renal medullary interstitial osm (contributes 50% interstitial osmolality) Result: concentrating ability kidney, H 2 O reabsorption SNS - activity with MAP - Effects: o Central: Stimulation thirst centre
Effect: input, correct deficit o CV: HR, SV CO o SVR Effect: Attempt to MAP, VR o Renal: Constriction afferent/efferent arterioles (α 1 receptors) o K f Effect: GFR, conserve H 2 O, Na + o Renal: renin release JGA granular cells (β 1 receptors) Effect: RAA activation RAA System - Renin released (above) cleaves angiotensinogen ATI lungs (ACE) ATII / ATIII adrenal cortex Aldosterone release - ATII (ATIII potent): o Peripheral: SVR by ATII binding AT 1 R direct constrictor Effect: Attempt MAP o Renal: constrict efferent > afferent arteriole Effect: GFR part of autoregulation o Renal: Na/H 2 O reabsorption PCT (AT 1 R) Effect: Retain H 2 O, Na + o Central: Stimulation hypothalamus, posterior pituitary Effect: Thirst, ADH release - Aldosterone: o Renal: H 2 O, Na + reabsorption DCT/CD aldosterone receptor principal cells Effect: Na/H 2 O absorption, K elimination
2006b(11)/2000a(7): List the hormones that regulate tubular reabsorption and describe their action and site of action Hormone Trigger Site of Action Action Angiotensin II Release of renin from JGA via SNS stimulation (β 1 receptors), local baroreceptor (stretch) 1 aff < eff arterioles Direct effect on PCT Adrenal HyTh Vasoconstriction GFR Na + reabsorption Aldosterone release Thirst, ADH release Aldosterone ADH (vasopressin) ATII, K + plasma, ACTH; prod n in adrenal cortex (zona glomerulosa) Post pituitary 2 stim n by hypothalamus ( osmolarity, MAP) CD induces prod n of Na,K-ATPase (basloateral) & K channels (luminal) CD camp - mediated insertion of aquaporins into duct membranes ANP atrial stretch Constrict efferent / dilate afferent arteriole / K f Principal cells K + excretion/na + absorption Type A cells H + secretion (K reabsorp n ) H 2 O reabsorp n urea reabsorp n medullary osmolarity Stimulates K + sec n /Na + absorp n GFR Inhibit RAA system ATII / Aldosterone ADH thirst / urine PTH [Ca 2+ ]extracellular β-adrenergic stim n CD PCT Late DCT Inhibits Na + reabsorp n (likely only a very small role) phosphate absorp n Ca 2+ reabsorp n ( Mg, H as well)
2007b(12): Outline the mechanisms by which the kidney maintains potassium homeostasis General: K + is 1 intracellular cation - Plasma conc 2 5 mmol/l Normal range is important - Cell membrane functioning (especially cardiac) Kidney - Glomerular filtration K = 5 x 180 = 900 mmol/day - Most filtered K is reabsorbed this rate is fixed o 55% PCT o 30% AscLoH - Also secreted into tubules main method of regulation - Urinary K conc not affected by primary changes in body Na or water Distal Convoluted Tubules (& cortical CD) 1. Principal Cells Secrete K - With normal dietary intake net effect is K excretion; K net effect is absorption - Main determinants: o Plasma K K directly stimulates basolateral Na/KATPase o Aldosterone also stimulated by K Induces production basolateral Na/KATPase production K channels in luminal membrane movement is down conc gradient therefore tubular flow rate K excretion o Plasma ph low H directly stimulates basloateral NA/KATPase 2. Type A Intercalated cells reabsorb K - Medullary CD always reabsorbs K
What are the functions of the kidney? Na.N.A.W.E.E.D Na balance / intravascular volume Nitrogenous waste excretion Acid-base excretion of titratable acid, HCO 3, NH 4 Water (total body) / osmolality Electrolyte balance Endocrine Drug biotransformation