P a g e| 1 Prepared by: Mar Mariano PHYSIO B 1.2 RENAL PHYSIOLOGY PT. 4 [DR. VILA] FEU-NRMF INSTITUTE OF MEDICINE 11.11.14 [1MD-D] Disorders of Urinary Concentrating Ability Impairment in the ability of the kidneys to concentrate or dilute the urineappropriatelycanoccurwithoneormoreofthefollowing abnormalities: 1.Inappropriate secretion of ADH 2.Impairmentofthecountercurrentmechanism.A hyperosmoticmedullaryinterstitiumisrequiredfor maximal urine concentrating ability. No matter how much ADHispresent,maximalurineconcentrationislimitedby thedegreeofhyperosmolarityofthemedullary interstitium. 3.Inabilityofthedistaltubule,collectingtubule,and collecting ducts to respond to ADH Failure to produce ADH: Central Diabetes Insipidus Also known ad pituitary diabetes insipidus Hypothalamus or posterior pituitary gland fails to produce or secrete ADH Large volumes of dilute urine (can exceed 15L/day) Inability ofthe kidneys torespond to ADH: NephrogenicDiabetes Mellitus Normal or elevated levels of ADH are present But renal tubules cannot respond Can be caused by: oFailure of countercurrent mechanism (Guyton) oFailure of distal and collecting ducts to respond to ADH (Guyton) oAbsenceofV2receptorsforADH(Accdg.to Dr.Vila) Large volumes of dilute urine Cancausedehydration,unlessfluidintakeisincreasedby the same amount as urine volume is increased Diabetes: common manifestation is polyuria Diabetes insipidus: secondary to ADH deficiency Diabetes mellitus: secondary to glucose No ADH Secretion / No response to ADH Decrease reabsorption of water Increase Urine Volume Decrease urine tonicity The Syndrome of Inappropriate ADH Secretion (SIADH) PlasmaADHelevated(asinsobrangtaas,abovewhat would be expected on the basis of the body fluid osmolality and, blood volume and pressure, kaya siya inappropriate) Water is retained, hence body fluid becomes hypoosmotic (more water, less concentrated ang body fluids) Urine is hyperosmotic Thetonicityofplasmadecreasesduetodilutional hyponatremia However,theamountofsodiumstillfallswithinnormal range It appears to be hyponatremic due to the increase in water reabsorption (dilution) Increase ADH Increase water reabsorption Decrease urine volume Increase urine tonicity Supposedly. Because of increase water reabsorption: Increase BV Increase BF Increase GFR Increase urine volume Initially, there is an increase in water reabsorption Eventually,theendeffectwillbeanincreaseinurine excretion due to increase blood volume Osmoreceptor-ADH Feedback System Example: Increase plasma osmolarity due to dehydration oFluidshiftfromtheinterstitiumintothe intravascular compartment oOsmoreceptorsarelocatedintheanterior hypothalamusnearthesupraopticnuclei [Guyton] oOsmoreceptorsaresensitivetochangesin osmolarity oAn increase in extracellular osmolarity will cause the osmoreceptors to shrink oSends signals to the hypothalamus to secrete ADH oADH enters blood stream towards the kidneys to increasewaterreabsorptionanddecreaseurine volume P a g e| 2 Prepared by: Mar Mariano Edema Excess fluid within the interstitial compartmentproducing visible swelling Increased capillary hydrostatic pressure Decreased plasma colloid osmotic pressure Edema caused by Heart Failure [Guyton, Chp. 25] Oneofthemostseriousandmostcommoncausesof edema In heart failure, the heart fails to pump blood normally from veins into the arteries, which raises the venous and capillary pressures, which eventually increases capillary filtration Increasecapillaryfiltrationlalabasangfluidsa interstitium edema Heart failure can also decrease blood flow to the kidneys DecreasebloodflowdecreaseNa+concentration detectedbymaculadensasecretereninbyJGcells activateangiotensinogentoangiotensinogenI conversiontoangiontensinIIbyACEinlungsrelease aldosteroneIncreasesaltandwaterretention Increase BV Increase capillary hydrostatic pressure Increase hydrostatic pressure edema Edema caused by Decreased Plasma Proteins [Guyton, Chp. 25] Oneofthemostimportantcausesofdecreasedplasma proteinconcentrationislossofproteinsintheurine Nephrotic syndrome Theglomerularbasementmembranewidens,thatallows the filtration of proteins Protein will therefore appear in the urine Proteinuria Therefore, there will be a decrease in plasma proteins Decreaseplasmaproteindecreaseplasmacolloid osmotic pressure edema LymphedemaFailureoftheLymphVesselstoreturnfluidand protein to the blood [Guyton, Chp. 25] Plasmaproteinstendtoleakintotheinterstitium,which can attract water and eventually cause edema The proteins be removed through the lymphatics Exampleoflymphobstructionsareinfectionswithfilaria nematodes (Wuchereria bancrofti) oBlocks lymph vessels oCauses lymphedema and elephantiasis oLocalized edema (limited to a one area only, [ex.] Extremities, penis, breast) Localized Edema 1.Venous obstruction 2.Capillary was damaged due to inflammation 3.Lymphatic obstruction Generalized Edema 1.Increase capillary hydrostatic pressure 2.Decrease plasma albumin Clinical Findings: oSwelling in most dependent parts of the body due toeffectsofgravityandincreasehydrostatic pressure in the capillaries Edema vs. Effusion Edema: fluid in interstitum Effusion:fluidinpotentialspacespleural,peritoneal, pericardial cavities, joint spaces Effect of Adding Saline Solution to the ECF [Guyton, Chp. 25] Principle of osmosis If a cell is placed in a hypotonic solution, the cell will swell (movement of water from extracellular to intracellular) However, the cell will not swell immediately ThecellwilltrytopumpoutelectrolytessuchasNa+,so that water will follow these electrolytes out of the cell and reduce swelling Thisiscalledregulatoryvolumedecrease(decreasecell volume to reduce swelling) If a cell is placed in a hypertonic solution, the cell will shrink, butnotimmediately(movementofwaterintracellularto extracellular) Electrolytesfromthesolutionwillmoveintothecell,and water will follow, hence reducing the shrinkage of the cell Thisiscalledregulatoryvolumeincrease(increasecell volume to reduce shrinkage) Fluid INFLUXECF Vol. ECF OP H2O Shift ICF Vol. ICF OP Compensatory Mechanism Isotonic Influx (2L NSS) SAME NONESAME SAME NONE Hypotonic Influx (Water loading) Extra to intracellular -DecreaseECF tonicity -Activate ADH -Water reabsorbed -Decrease urine volume -Increase urine tonicity Hypertonic Influx (Drink sea water) Intra to extracellular -IncreaseECF tonicity -Inhibit ADH -Increase urine volume -Decrease urine tonicity P a g e| 3 Prepared by: Mar Mariano Fluid EFFLUXECF Vol. ECF OP H2O Shift ICF Vol. ICF OP Compensatory Mechanism Isotonic Efflux (Burns) SAME NONESAME SAME NONE Hypotonic Efflux (Profuse Sweating) Intra to extracellular -High ECF tonicity -Activate ADH -Water reabsorption -Decrease urine volume -Increase urine tonicity Hypertonic Efflux (SIADH) Extra to intracellular -Low ECF tonicity -Inhibit ADH -Increase urine volume -Decrease urine tonicity Acid-Base Balance Acid: a substance that can release or donate hydrogen ion [H+] Base:asubstancethatcancombinewithoraccept hydrogen ion [H+] Normal blood pH: 7.35 7.45 Normal pCO2: 35 45 mmHg Normal pCO3-: 22 26 mmHg pO2 is less important *Respi Physio Review* Oxygen-Hemoglobin Dissociation Curve Hemoglobin carries oxygen However,hemoglobinneverreaches100%oxygen saturation. Why? oAll the blood that reaches the lungs will be 100% oxygenated oFromthelungs,andalongwiththebloodfrom different veins, will drain into the heart oVeins carry less oxygenated blood oBlood that comes out of the aorta will only be 97-98%saturatedwithoxygenbecauseitwillbe mixed with less oxygenated blood from the veins oAt 60mmHg, the saturation slows down oBelow 60mmHg, saturation is steep (Hgb unbinds immediately from oxygen) oIn real situations, we never go below 60mmHg opCO2: respiratory component oRepresent acid oExcreted by lungs oIncrease pCO2: Acidic oDecrease pCO2: Basic opCO3-: metabolic component oRepresent base oExcreted by kidneys oIncrease pCO3-: Basic oDecrease pCO3: Acidic Decrease pH: acidosis Increase pH: alkalosis Rules: Always follow the pH If fully compensated: pH will go back to normal oIf pH is slightly toward alkaline but within normal range: alkalosis, fully compensated oIfpHisslightlytowardacidicbutwithinnotmal range: acidosis, fully compensated If partially compensated: pH of blood is still abnormal pH (7.35 7.45) pCO2 (35 45 mmHg) pCO3- (22 -26mmHg) Disorder 7.29Acidic48Acidic24Normal Respiratory Acidosis 7.29Acidic37Normal19Acidic Metabolic Acidosis 7.47Basic32Basic24Normal Respiratory Alkalosis 7.47Basic37Normal29Basic Metabolic Alkalosis 7.29Acidic36Normal19Acidic Metabolic Acidosis 7.47Basic32Basic19Acidic Respiratory Alkalosis, partially compensated by the kidneys 7.47Basic48Acidic29Basic Metabolic Alkalosis, partially compensated by lungs 7.29Acidic30Basic28Basic Mixed Acidosis, partially compensated 7.47Basic30Basic19Acidic Respiratory Alkalosis, partially compensated 7.44Normal48Acidic30Basic Metabolic Alkalosis, fully compensated 7.38Normal48Acidic30Basic Respiratory Acidosis, fully compensated P a g e| 4 Prepared by: Mar Mariano pH Units In the events of everyday life, the variation of ECF pH is very narrow 1nmol of H+/L = 0.01 pH unit oIf H+ ions increase: pH decrease, pH is acidic oIf H+ ions decrease: pH increase, pH is basic In abnormal situations, much wider changes may be seen. In practice, a pH of 6.8 or 7.8 will only be seen in profound pathologic situations Sources of H+ ions in the body Metabolism of food stuffsoProduces 300L of CO2 Incomplete metabolism of CHO and fats oProduces nonvolatile acids oLacticacidfromglucose,acetoaceticacidand Beta-hydroxybutyricacidfromfattyacid oxidation Oxidation of proteins and amino acids oProduces strong acids oH2SO4, HCl and H3PO4 Bodys defenses against changes in blood pH Chemical buffers in ECF, ICF and bone oFirst line of defense of blood pH oMinimized a change in pH but cannot remove acid or base from the body Respiratory system oSecond line of defense oLargeloadsofacidstimulatebreathingwhich removes CO2 from the body Kidneys oThird line of defense oRemove excess H+ from the body in combination with urinary buffers Henderson-Hasselbach Equation Shows that the pH of a solution is determined by the pKa of acid and the ratio of the concentration of conjugate base A- and acid HA Bicarbonate Buffer System: Kidneys [Berne&Levy Chp. 36] The most important ECF buffer In the proximal tubules: Theproximaltubulereabsorbsthelargestportionofthe filtered load of HCO3- H+ secretion across the apical membrane of the cell occurs by Na+H+ antiporter and H+-ATPase Carbonicanhydrasearepresentinthebrushbordersthat convert H2CO3 to water and carbon dioxide They enter the cells and combines to produce H+ and HCO3 by carbonic anhydrase H+ is secreted via apical membrane, HCO3- via basolateral membrane HCO3 exit via a symporter: 1Na+ with 3HCO3 Some of the HCO3 may exit in exchange for Cl- AK+-HCO3-symporterinthebasolateralmembranemay also contribute to the exit of HCO3- from the cell In the collecting ducts There are 2 types of cells: oPrincipal cells responsible for electrolyte and fluid absorption oIntercalated cells for acid-base balance There are 2 types of intercalated cells oAlpha-intercalatedcells:secreteH+(reabsorbs HCO3-) oBeta-intercalated cells: secrete HCO3- Within Alpha-intercalated cells: oH+ and HCO3- are producedby the hydration of carbondioxide,whichiscatalyzedbycarbonic anhydrase P a g e| 5 Prepared by: Mar Mariano oH+ is secreted into the tubular fluid via: Apical membrane H+-ATPase H+,K+-ATPase oHCO3-exitsacrossthebasolateralmembranein exchange for Cl-, via a Cl-HCO3- antiporter oActive during metabolic acidosis Within Beta-intercalated cells oH+-ATPaseislocatedinthebasolateral membrane oCl-HCO3-antiporterislocatedintheapical membrane [Baliktad sila ng alpha-intercalated] oActivityofbeta-intercalatedcellsisincreased duringmetabolicalkalosis,whenthekidneys must excrete HCO3- Acid-Base Balance via excretion of ammonium NH4+: ammonium, acidic NH3: ammonia NH4+isproducedbythekidneysbythemetabolismof glutamine The kidneys metabolize glutamine, excrete NH4+, and add HCO3- to the body If NH4+ is not excreted in the urine, it is converted into urea by the kidneys, which produces H+, and eventually buffered by HCO3- Production of urea, therefore, consumes HCO3- and inhibits HCO3-formationthroughthesynthesisandexcretionof NH4+ NH4+ is produced from glutamine via ammoniagenesis One glutamine molecule produces two NH4+ molecules and two HCO3- molecules HCO3- exits the cells across the basolateral membranes and enters the peritubular blood NH4+exitsviaapicalmembraneandentersthetubular fluid, via NA+-H+ antiporter, but NH4+ is substituted for H+ NH3isfreelypermeableandcandiffuseoutofthecell where it is protonated into NH4+ ThethickascendinglimbistheprimarysiteofNH4+ reabsorption,withNH4+substitutingforK+onthe1Na+-K+-2Cl- symporter The NH4+ that is reabsorbed, accumulates in the medullary interstitium which is then secreted into the collecting ducts via: oNonionic diffusion oDiffusion trapping NH3diffusesfromthemedullaryinterstitiumintothe collecting ducts (nonionic diffusion) ThepresenceofAlpha-intercalatedcellswhichsecreteH+ ions will protonate the NH3 to become NH4+ SinceNH4+islesspermeableinthecollectingducts,itis trapped in the tubular lumen (diffusion trapping) It is then eliminated from the body via the urine Please refer to Guyton for the Phosphate Buffer System and Proteins asICFbuffers,andGuytonChp.36Acid-BaseBalance(Hindina diniscuss ni doc, pero kasama daw sa shifting ) Reading assignments: Renal Failure Renal Endocrine Function Sources: Lecture: Dr. Vila Berne&Levy, 6th Edition Guyton and Hall, 12th Edition Read Berne & Levy or Guyton, guys! Mas specific at complete mga explanations dun. Good luck and God bless! Labyu all