04/13/2023 Dr. Ashok Kumar J; IMS; MSU 1

RENAL REGULATION OF pH

Dr. Ashok Kumar JInternational Medical School

Management and science universityMalaysia

04/13/2023 Dr. Ashok Kumar J; IMS; MSU 2

RENAL MECHANISM

Kidney plays a major role in acid-base regulation

2. Reclamation the bicarbonate ions present in the ultra-filtrate

1. Excretion of H+

3. Excretion of titrable acid 4. Excretion of ammonia

04/13/2023 Dr. Ashok Kumar J; IMS; MSU 3

1. EXCRETION OF H+

- Occurs in proximal tubule

- CO2 combines with H2O to form H2CO3

- It dissociates to form HCO3- and H+

- H+ is secreted in exchange for Na+

- Net production of HCO3- and net excretion

of H+

- mechanism serves to increase

the alkali reserve

HCO3-HCO3

-

H2O + CO2 H2CO3-

H+ H+

Tubular cellTubular Lumen

Na+Na+

04/13/2023 Dr. Ashok Kumar J; IMS; MSU 4

HCO3-HCO3

-

H2O + CO2 H2CO3-

H+ H+HCO3

-+

H2CO3-

H2O CO2 + CO2

Tubular cell Tubular Lumen

2. RECLAIMATION THE BICARBONATE IONS PRESENT IN THE ULTRAFILTRATE

04/13/2023 Dr. Ashok Kumar J; IMS; MSU 5

HCO3-

H2O + CO2 H2CO3-

H+

NH4+

H+

Tubular cell

Tubular Lumen

NH3

Titrable acid

Na2HPO4-

NaH2PO4-

GLUTAMIN

GLUTAMATE

Glutaminase NH3

04/13/2023 Dr. Ashok Kumar J; IMS; MSU 6

•NH3 (ammonia) freely crosses the cell membrane enters the lumen of renal tubule

•Combines with protons present in the filtrate to form NH4 (ammonium ions)

•Ammonium ions are impermeable through the cell membrane – excreted in urine

•Daily excretion in urine 60 mEq/L of H+ excreted as Ammonia

04/13/2023 Dr. Ashok Kumar J; IMS; MSU 7

When there is an excess of acid production in the body, H+ are excreted in urine as titrable acid and ammonia

• Titratable acidity of urine : The number of milliliters of N/10 (0.1N) NaOH

required to titrate 1 liter of urine to pH 7.4.

• This is a measure of net acid excretion by the kidney

04/13/2023 Dr. Ashok Kumar J; IMS; MSU 8

Anion GapIn Extracellular fluidSum of anions = Sum of cations - Electrical neutrality

•Sodium (Na+) and Potassium (K+) together accounts for 95% of the cations

•Chloride and bicarbonate accounts for only 86% of the anions

• Measured cationsSodium 136 mEq/LPotassium 4 mEq/L

• Unmeasured CationCalcium 4.5 mEq/LMagnesium 1.5 mEq/L

• Measured anionsChloride 98mEq/LBicarbonate 25mEq/L

• Unmeasured anionProtein 15mEq/LPhosphate 2mEq/LOrganic acids 5mEq/LSulfate 1mEq/L

04/13/2023 Dr. Ashok Kumar J; IMS; MSU 9

• Unmeasured anions constitute the anion gap

• Calculated as difference between measured cations and measured anions

Anion Gap = (Na+ + K+) - (Cl- + HCO3-)

• Normal is about 12 mEq/L

e.g: = ( 140 + 4) – (103 + 25) = 16

04/13/2023 Dr. Ashok Kumar J; IMS; MSU 10

Disturbance in acid base balance

Acidosis : Clinical state where acids accumulate or bases are lost Alkaosis : Clinical state where accumulation of base or loss of acids

[Bicarbonate]pH = pKa + log10

[Carbonic acid]

04/13/2023 Dr. Ashok Kumar J; IMS; MSU 11

[Bicarbonate][Carbonic acid]

pH = pKa + log10

Regulated by KidneyMetabolic component

Decreased BicarbonateDecreases the ratioDecreases pHMETABOLIC ACIDOSIS

ACIDOSIS

Metabolic acidosis :- Primary alkali (bicarbonate) deficit

04/13/2023 Dr. Ashok Kumar J; IMS; MSU 12

[Bicarbonate][Carbonic acid]

pH = pKa + log10

Regulated by KidneyMetabolic component

Increased BicarbonateIncreases the ratioIncreases pHMETABOLIC ALKALOSIS

ALKALOSIS

Metabolic alkalosis :- Primary alkali (biocarbonate) excess

04/13/2023 Dr. Ashok Kumar J; IMS; MSU 13

Metabolic acidosis

Increased production of hydrogen ions

• Diabetic ketoacidosis ; Starvation ketoacidosis; Lactic acidosis ; Salicylate intoxication

Impaired excretion of hydrogen ions

• Renal failure ; Renal tubular acidosis type II

Loss of bicarbonate from the gastrointestinal tract or in urine

• Severe diarrhoea ; Renal tubular acidosis type I; Ureterosigmoidostomy

04/13/2023 Dr. Ashok Kumar J; IMS; MSU 14

Loss of bicarbonate a. From gastrointestinal tract as in • severe diarrhoea

b. From the kidney as in• Ureterosigmoidostomy• Renal tubular acidosis

is replaced by chlorideResults in hyperchloremic acidosis

04/13/2023 Dr. Ashok Kumar J; IMS; MSU 15

04/13/2023 Dr. Ashok Kumar J; IMS; MSU 16

BUFFER SYSTEM

Mainly bicarbonate buffer minimizes change in pH

HCO3 concentration is decreased and ratio of HCO3/H2 CO3 less than 20/1

RESPIRATORY MECHANISM

Increases rate and depth of respiration (Kussumauls breathing)

Elimination of carbonic acid as CO2 ,

Decrease in pCO2 and consequently decrease in H2CO3

04/13/2023 Dr. Ashok Kumar J; IMS; MSU 17

RENAL compensation seta in 2 to 4 days

Increases excretion of acid and preserves the base by increased rate of

Na- H exchange

Increases ammonia formation and increased reabsorption of HCO3

04/13/2023 Dr. Ashok Kumar J; IMS; MSU 18

• Uncompensated Metabolic acidosis• Partially compensated Metabolic acidosis• Compensated Metabolic acidosis

Fully compensated

Partially compensated

uncompensated

Normal decreased decreased pHDecreased decreased normal pCO2

Decreased decreased decreased HCO3

pO2

04/13/2023 Dr. Ashok Kumar J; IMS; MSU 19

Metabolic alkalosis• Raise in the plasma bicarbonate• Loss of H+ ions

CAUSES : • Loss of gastric juice along with H+ ions as in

- prolonged vomiting, - Nasogastric succion etc

•Therapeutic administration of large dose of alkali – chronic intake of excess antacids - Intravenous administration of bicarbonateetc

04/13/2023 Dr. Ashok Kumar J; IMS; MSU 20

RESPIRATORY MECHANISM:

Increase in pH depresses the respiratory center, causes retention of CO 2

pCO2which in turn increases the H 2CO 3 .

RENAL MECHANISM:

Kidney decreases H+ excretion

decreased reclamation of bicarbonate.

COMPENSATORY MECHANISM

04/13/2023 Dr. Ashok Kumar J; IMS; MSU 21

Fully compensated

Partially compensated

uncompensated

normal increased increased pHincreased increased normal pCO2

increased increased increased HCO3

pO2

04/13/2023 Dr. Ashok Kumar J; IMS; MSU 22

Thank you