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Metabolic AlkalosisHigh pH HighHCO3 High pCO2

Development of Metabolic Alkalosis

Generation of Excess HCO33HCO3 Ingestion or Acid Loss

Maintenance of Excess HCO3Maintenance of Excess HCO3Increased renal H+ secretion

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Metabolic AlkalosisGeneration of Excess HCO3

HCO3 Ingestion

HCO3 Generation from metabolizeable anions e.g. lactate, citrate or β-OH butyrate

Metabolic Alkalosis

Acid Loss

vomiting ; upper GI suction

Generation of excess HCO3 is often necessary

to produce alkalosis, BUT, it is insufficient since

the kidney’s ability to excrete HCO3 is very large

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Maintenance of Metabolic Alkalosis

The higher level of HCO3 is maintained by increased renal H+ secretion

1. Decreased Filtration Rate2. Volume Depletion increases Proximal

HCO3 Reabsorption by a. High Filtration Fractiona. High Filtration Fractionb. AII stimulates Na:H exchanger

3. High aldosterone increases collectingduct H+ secretion and HCO3 generation

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Potassium

Intracellular Extracellular

[K] = 110 mEq / L[Na] = 10 mEq / L

[K] = 4 mEq / L[Na] = 140 mEq / L

Total Body K 4400 mEq 50 mEq

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K

4

Time, hrs

Disposal of an ingested K Load occurs by re-distributionand by urinary excretion

K

Acidosis

4Alkalosis

Time, hrs

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K

Diabetes

4Insulin

Time, hrs

K

β blockers

4Epinephrin

Time, hrs

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PCT DCT

ThAL CDThAL

K is Freely Filtered s ee y te ed

> 95% of Filtered K is reabsorbed in the Proximal Tubule and Thick Ascending Limb

What appears in the Urine is secreted by the Distal Tubule and Collecting Duct

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K Secretion in Collecting Duct

NaK

ENaC

KNa

K

ENaC Epithelial Na ChannelK K channel

H,K ATPase

Driving Forces for K Secretionin Collecting Duct

KK

-100 mV

0

Concentration GradientTrans-epithelial Membrane Potential

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0.3

0.35N

Hi K diet

0 05

0.1

0.15

0.2

0.25

Low K diet

0

0.05

0 5 10 15 20 25 30 35

Tubule Flow rate, nanoL/min

Regulation of K Secretion

Na ENaCK

Na

K

Aldosteroneincreases activity of K channelincreases activity of Na channelincreases Na,K ATPase

KK

Urine Flow Ratebrings in low K tubular fluid

Acid Base balance affects Cell K

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Approach to the patient withHypo- or Hyperkalemia

1. Redistribution Acid/Base status, insulin, catecholeamines

2. Intake dietary;; Intravenous

3. Renal Excretion Aldosterone, Urine Flow Rate, Acid/Base statusRenal FailureInterstitial Disease

4. Non-Renal Loss Gastro-intestinalSweat

HypokalemiaRedistribution

Alkalosis; Glucose/insulin; Catecholeamines

Increased ExcretionHyperaldosteronism

primary: (including Cushing’s Syndrome)secondary: CHF, volume depletion, cirrhosis

Increased Urine Flow Rate DiureticsAlkalosisDrugs Amphotericin B

Extra-renal Loss Sweating; Diarrhea; Vomiting

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Clinical Manifestations of HypokalemiaMuscle Weakness eventually paralysis;

occasionally rhabdomyolysis

RT aKiMembrane Potential ΔΨ = - ln

F aKo

C di th iCardiac arrythmias

Clinical Manifestations of Hypokalemia

Effects on Renal FunctionInhibition of concentrationIncreased HCO3 reabsorptionIncreased NH3 production

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Hyperkalemia

RedistributionAcidosis; Diabetes β-blockers; β

Increased IntakeOral or I.V. (with Renal Failure)

Decreased ExcretionLow AldosteroneDecreased Flow RateAcidosisDrugs

Hyperkalemia

Decreased Excretion-Hypoaldosteronism

primary: Addison’s Diseasesecondary: Hyporeninemic Hypoaldosteronsim

ACE inhibitors-Decreased Urine Flow Rate

Acute Renal Failure with oliguriag-Acidosis-Drugs K sparing diuretics

NSAIDsHeparin

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Clinical Manifestations of Hyperkalemia

Cardiac Arrythmia

Hyperkalemia can induce acidosis by inhibiting NH3 production in the nephron

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