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1、DisordersofPotassiumMetabolismOutline I.Normal potassium metabolism and regulationII.HypokalemiaIII.HyperlalemiaIV.Case discussion1.thetotalpotassiumofbody:intracellular:98（140-160mmol/L）extracellular：2（3.5-4.5mmol/L）I.Normalpotassiummetabolism2.potassiumpresentsinthefood,suchasmilk,peanutpotatoes,s
2、altsubstitute.Potassium excrete pathway:kidney through urine:90 Stool(feces):10Sweatnormal serum potassium:3.5-5.5mmol/Lbalance between intra-and extracellular K+normal:15 h3.regulationofpotassiumhomeostasisTranscellulartransferRenalregulation(1)PotassiumtranscellulartransferPump-leakmechanismfactor
3、s:PotassiumconcentrationinECFAcid-basebalanceInsulinCatecholamineOsmolarityExerciseTotalbodypotassium(2).RenalregulationforpotassiumexcretionGlomerular filtrationReabsorption by the proximal tubule and the loop of HenleRegulation of potassium excretion in the distal and collecting tubulesSodium-pota
4、ssium ATP ase Permeability of luminal membrane for potassiumReabsorption in collecting tubules Hydrogen-potassium ATP ase-proton pumpMechanismofpotassiumexcretionindistalandcollectingtubules:Influencing factors of potassium excretion in distal and collecting tubules:Potassium concentration in ECFAld
5、osteroneDistal flow rateAcid-base balance(3)Potassium excretion in colon The same as the excretion in kidney4.physiologicalfunctionofpotassium maintain cellular metabolism maintain cellular resting membrane potential regulate the osmolarity and acid-base balanceDisorderofpotassiummetabolismNormal se
6、rum potassium:3.5-5.5mmol/LHypokalemiaHyperkalemia 5.influencing facter of potassium homeostasis acidosis alkalosis hypoxia serum insulin serum damage of cells K+ADS K+catabolism anabolism distal flow rate distal flow rate1.Definition:Hypokalemiaisdefinedasadecreaseinserumpotassiumlevellessthan3.5mm
7、ol/L.hypokalemia2.causes(1).intake(2).dischargedigestivetractkidneys：skin GI:vomiting;diarrhea;Gastrointestinal suction Skin:excessive sweats furosemide diuretic losses diamox diuretic phase of ARF renal:primary hyperaldosteronism lack of magnesium renal tubular acidosis osmotic diuresis(3).Abnormal
8、itydistributionofpotassiummoveintocellsacute alkalosis insulin overdose Barium poisoningBeta-receptor excitomotoryhypokalemic periodic paralysis3.alterationsofmetabolismandfunctionNerve cellsskeletal muscles gastrointestinal smooth muscleMyocardial cells Effects on body (1).nerves and muscles acute
9、hypokalemia excitability 0 mv serumK+-30mv AP -60mv TP(Et)-90mv RP(Em)hyperpolarization(2).Heart arrhythmia 0 mv serumK+-30mv -60mv -90mv depolarization Excitability:K+ECF K+permeability depolarization repolarization excitability ECG T wave Conductivity:RP 0 phase of AP conductivity conductive block
10、 unidirectional block ECG P-R Autorhythmicity:Contractility:acute ;chronic effects on heart cardiac excitability cardiac conductivity cardiac automaticity cardiac contractibility (3).Renal polyuria (sensitivity of ADH)(4).GI smooth muscles Hyperpolarization(5).acid-base balancemetabolic alkalosis pa
11、radoxical aciduria4.principlesofpreventionandtreatment1.treatmentofprimarydisease2.principlesofpotassiumcompensationoral application is better Give potassium according to the urine concentration 40mmol/L，slowly 10-20mmol/htoobserve：heart rate cardiac rhythm consciousness acid base1.definition:hyperk
12、alemia is defined as serum potassium exceeding 5.5mmol/L.hyperkalemia2.causes(1).increased intake of potassium(2).Impaired renal potassium excretion：renal dysfunction ALD potassium-sparing diuretics(3).abnormalpotassiumtranscellularditributionacuteacidosishypoxiaATPtissuedamagehyperkalemicperiodicpa
13、ralysisDiabetesBeta-receptorinhibbitor3.alterationsofmetabolismandfunction(1).effect on neuromuscular excitability:(2).effects on heart cardiac excitability cardiac conductivity cardiac automaticity cardiac contractibility (3).effect on the acid-base balance acidosis paradoxical alkaline urine skele
14、tal muscle 8mmol/L RP (depolarization)excitability stabbing;tremor 8mmol/L RP inactivation of Na+channel depolarization paralysis heart(hyperkalemia K+permeability )5.5-7mmol/L RP E excitability 7-9mmol/L RP E 7-9mmol/L RP E T wave ;QT shortcardiac arrestPR QT Autorhythmicity:K+out ward of phase 4 S
15、pontaneous depolarization heart rate Conductivity:RP Na+inward of phase 0 conductivity conductive block unidirectional block Contractility:inhibition of Ca2+inward flow contractilityacid-base balanceacidosis paradoxical alkaline urine4.principlesofpreventionandtreatmenta)treatment of primary disease
16、 b)decrease uptake of K+c)cut down total amount of body potassium dialysis ion-exchange resind)induce K+uptake by cells.e)application of calcium and sodiumSummaryI.NormalpotassiummetabolismandregulationII.HypokalemiaIII.hyperkalemiadefinitioncausesalterationsofmetabolismandfunctionprinciplesofpreven
17、tionandtreatmentIV.Casepresentation The pH of the ECF is maintained within the narrow range of 7.357.45 7.8 !I.Acid-base homeostasis 1.The acids and bases in the blood 1)AcidsRespiratory acid(Volatile acid)H2CO3 CO2+H2O H2CO3 H+HCO3-Metabolic acid The product of metabolism of amino acid:phosphophory
18、n,nucleric acid phosphoric acid methionine,cysteine sulfuric acid purine uric acid (gout)Lactic acid(The liver removes and converts to G)Ketoacids(pyruvic acid,acetoacetic acid,hydroxybutyric acid)2)Base The fruits and vegetables are rich in alkali salt,e.g.sodium citrate,potassium citrate.2.Control
19、 of pH 1)The buffer systems Buffers are the first defense against pH disorders,and act immediately.Alkali salt of the acid Buffer system:Weak acid NaHCO3 Bicarbonate buffer pair H2CO3 To buffer metabolic acid and base in ECF Hb buffer pairs in RBC to buffer respiratory acid.HPO42-Phosphate buffer pa
20、ir H2PO4-To buffer in ICF 2)Respiratory contribution The respiratory system is the second defense against pH disorders,and needs several minutes.H2CO3 The rate and depth H2CO3 H+But when PaCO2 80mmHg,the rate and depth.H2CO3 The rate and depth H2CO3 H+3)Renal contribution The kidney is the third def
21、ense against acid-base disorders.Metabolic acid Excretion of acid Reabsorption of baseMetabolic acid Excretion of acid Reabsorption of base Base Excretion of acid Excretion of baseThe kidneys can compensate for respiratory acid imbalances by excretion of metabolic acids.(Indirectly)H2CO3 Excretion o
22、f metabolic acid H2CO3 Excretion of metabolic acid The renal compensation requires several days to be fully effective.4)Effects of K+and Cl-on pH regulation Acidosis can cause hyperkalemia,and alkalosis can cause hypokalemia.H+K+HCO3-Cl-3.The determination of pH pH=pKa+logHCO3-/H2CO3 If the ratio is
23、 20:1,the pH will be 7.44.The main indicators of laboratory about acid-base balance 1)pH:The normal range is 7.357.45 A normal range of pH represents No disturbance in acid-base balance Acid-base imbalance with complete compensation A mixed acidosis and alkalosis which have opposite effect on pH and
24、 offset each other.3 situations:2)PaCO2:Normal range is 3842mmHg(40mmHg).(3346mmHg)PaCO2 is an indicator of the effectiveness of respiratory excreting of carbonic acid.If PaCO2,means hypoventilation or metabolic alkalosis after compensation PaCO2,means hyperventilation or metabolic acidosis after co
25、mpensation3)HCO3-:The normal range is 24 33mmol/L.It is an indicator of the renal excretion of metabolic acid.HCO3-means an excess of metabolic acids(metabolic acidosis or respiratory alkalosis after compensation).HCO3-means a deficit of metabolic acids or an excess of base(metabolic alkalosis or re
26、spiratory acidosis after compensation).Standard bicarbonate SB(2227mmol/L)Actual bicarbonate AB ABSB,hypoventilation;ABSB,hyperventilation Buffer base BB Base excess BE CO2 combine power（CO2CP）4)AG(aniongap):AG describes the difference between unmeasured anion(UA)and unmeasured cation(UC).AG=Na+-(Cl
27、-+HCO3-).The normal range is 10 14 mmol/L(12 mmol/L).II.Acid-baseimbalances1.Metabolicacidosis1)Concept:Metabolic acidosis refers to a primary deficit in base bicarbonate,the pH falls.2)Causes:(1)Increaseinmetabolicacids Excess production of metabolic acids E.g.fasting and starvation,diabetic ketoac
28、idosis,lactic acidosis(shock,hypoxia,heart failure,anemia).Decreased loss of metabolic acids E.g.renal failure,renal tubular acidosis-I Over dose of acidic medicine(aspirin).AG is increased.(2)Increase in bicarbonate loss E.g.Severe diarrhea,intestinal fistulas Renal tubular acidosis-II.Over dose of
29、 NH4+,releases HCl AG is normal.3)Compensation:(1)Buffer system and cell (2)Signs of compensation Kussmaul breathing Acid urine4)Manifestations (1)Heart failure:Hyperkalemia _cardiac arrhythmia Impair myocardial contraction (2)Decreased response of capillary to catecholamines _Shock (3)Depression of
30、 neural function Lethargy,disorder of consciousness,coma.(4)Changes of osseous system Renal rickets肾性佝偻病,osteomalacia骨软化症4)Laboratory findings pH,HCO3-,PaCO2 if there is compensation of respiratory system.Case study:Arterial blood:pH 7.21 PaCO2 26 mmHg PaO2 108 mmHg HCO3-12 mmol/L Na+135 mmol/L K+2.
31、0 mmol/L Cl-110 mmol/L Urine:pH 5.0(1)A 36-year-old man was hospitalized with a 3-day history of fever and watery diarrhea.The blood pressure is 90/60 mmHg,the pulse is 112/minute,the respiratory rate is 24/minute,and the temperature is 37.5C.The laboratory results were obtained.2.Respiratory acidos
32、is 1)Concept:Respiratory acidosis is defined as a decrease of pH induced by primary increase in plasma H2CO3.2)Causes Respiratory acidosis can occur as an acute or a chronic disorder.(1)Acute respiratory acidosis E.g.acute respiratory infections,chest injuries,pulmonary edema.(2)Chronic respiratory
33、acidosis E.g.chronic obstructive lung disease,chronic bronchitis.3)Compensation:Buffer system and cell4)Manifestations:Headache,cardiac arrhythmias and neurologic abnormalities.Neurologic manifestations may be more prominent in respiratory acidosis than in metabolic acidosis.“CO2 narcosis”The mechan
34、ism:(1)CO2 crosses the blood-brain barrier relatively easily,and can dilate the blood vessels in the brain and lead to brain edema.(2)CO2 can also decrease the pH of the cerebrospinal fluid,and make depression of neural function,like weakness,confusion,paralysis,stupor and coma.5)Laboratory findings
35、 pH,PaCO2,HCO3-if there is compensation of kidneys(chronic).3.Metabolic alkalosis 1)Concept:Metabolic alkalosis refers to a primary increase in base bicarbonate,the pH elevates.2)Causes:(1)Decrease of acid E.g.vomiting (Ileus:intestinal obstruction).(2)Increase of base E.g.antacids,transfusion with
36、citrated blood,hyperaldosteronism.Saline-responsive alkalosis and saline-resistant alkalosis3)Compensation4)Manifestations Alkalosis can cause increased excitability of nervous system,like hyperactive reflexes,muscle hypertonicity,tetany etc.5)Laboratory findings pH,HCO3-,PaCO2 if there is compensat
37、ion of respiratory system.4.Respiratory alkalosis 1)Concept:Respiratory alkalosis is defined as an increase of pH induced by primary decrease in plasma H2CO3.2)Causes:Hyperventilation E.g.anxiety,hysteria,fever,early salicylate(aspirin)toxicity,misuse of mechanical ventilation.3)Compensation4)Manife
38、stations Tetany 5)Laboratory findings pH,PaCO2,HCO3-(depend on the normal renal function).5.Mixed acid-base imbalancesConcept:Two or more primary acid-base imbalances exist at the same time.BacterialpneumoniarespiratoryacidosisPatientDiarrheametabolicacidosisIn this mixed imbalance,the pH is likely
39、to be very low.PneumoniarespiratoryacidosisPatientVomitingmetabolicalkalosisIn this mixed imbalance,the pH will change slightly or in normal range.Acidosis+acidosis,or alkalosis+alkalosis,the pH will change a lot;acidosis+alkalosis,the pH will change slightly or in normal range.Respiratory acidosis
40、and respiratory alkalosis can not exist at the same time.(2)A 32-year-old male presented with vomiting of one weeks duration.On examination,he had a blood pressure of 90/60 mmHg and a pulse of 116/minute.See the laboratory results.Arterial blood:pH 7.55 PaCO2 46 mmHg HCO3-39 mmol/L Na+143 mmol/L K+2
41、.7 mmol/L Cl-72 mmol/L Urine pH 5.0(3)A 52-year-old man with chronic obstructive lung disease is admitted to the hospital with worsening dyspnea.He appears cyanosis and in respiratory distress.The laboratory data follow.Arterial blood pH 7.34 PaCO2 60 mmHg PaO2 50 mm Hg HCO3-35 mmol/L Na+136mmol/L K+4.9 mmol/L Cl-96 mmol/L (4)A 48-year-old female presented with severe vomiting.On examination,T 38,HR 89/min,R 26/min,Bp 150/100 mmHg.She appears general edema.The laboratory results Arterial blood pH 7.39 PaCO2 43 mmHg PaO2 95 mm Hg HCO3-26 mmol/L Na+142mmol/L K+3.6 mmol/L Cl-98 mmol/L