Acid-Base Balance • Refers to precise regulation of free H+ concentration in body fluids • Acids – Group of H+ containing substances that dissociate in solution to release free H+ and anions
• Bases – Substance that can combine with free H+ and remove it from solution
• pH – – – –
Designation used to express the concentration of H+ pH 7 – neutral pH less than 7 → acidic pH greater than 7 → basic
Acid-Base Balance • Arterial pH less than 6.8 or greater than 8.0 is not compatible with life • Acidosis – Exists when blood pH falls below 7.35
• Alkalosis – Occurs when blood pH is above 7.45 Plasma hydrogen conc = 40 nmol/l
pH
Acid-Base Balance • Consequences of fluctuations in pH – Changes in excitability of nerve and muscle cells – Marked influence on enzyme activity – Changes influence K+ levels in body
Sources of H+ gain and loss • H+ Gain – – – –
CO2 in blood (combine with H2O via carbonic anhydrase) Nonvolatile acids from metabolism (e.g. lactic) Loss of HCO3- in diarrhoea or non-gastric GI fluids Loss of HCO3- in urine
• H+ Loss – Loss of H+ in vomit – Loss of H+ in urine – Hyperventilation (blow off CO2)
• Loss of H+ like gaining HCO3• Loss of HCO3- like gaining H+
Lines of Defense Against pH Changes
• Chemical buffer systems • Respiratory system • Kidneys
Chemical Buffer Systems • Minimize changes in pH by binding with or yielding free H+ • First line of defense • Body has four buffer systems – H2CO3-, HCO3- buffer system
• Primary ECF buffer for noncarbonic acids
– Protein buffer system • Primary ICF buffer; also buffers ECF
– Hemoglobin buffer system • Primary buffer against carbonic acid changes
– Phosphate buffer system • Important urinary buffer; also buffers ICF
Carbonic Acid – Bicarbonate Buffer System
Respiratory component
Renal component Carbonic anhydrase
CO2
+
H 2O
H2CO3 Carbonic acid
H+
+ HCO3 –
bicarbonate
(H2CO3 is a ‘volatile’ acid as → CO2 exhaled ) pH = pKa + log10 [HCO3-] PCO2
Kidneys • Third line of defense against change in hydrogen ion concentration • Kidneys require hours to days to compensate for changes in body-fluid pH • Control pH of body fluids by adjusting – H+ excretion – HCO3- excretion – Ammonium excretion
CO2
HCO3- + H+
HCO3-
H+ : Phosphoric acid, NH4+
HCO3- reabsorption and H+ secretion in PCT
Na+
ATPase
K+
HCO3-
Cl-
Addition of new HCO3- to plasma by secretion of H+
• When you use up filtered HCO3- in tubule and still have excess H+ (acidosis), then you must combine H+ with another buffer e.g. HPO42-. • Unusual since lots of HCO3- in tubular fluid! • Gives net gain of HCO3- to plasma.
Addition of new HCO3- to plasma by excretion of ammonium (NH4+) • Another way of adding HCO3- to plasma by metabolising glutamine. • Takes long time, usually only occurs in chronic acidosis e.g. diabetes.
glutamine
Glutamine deamination ammoniagenesis
Acid-Base Imbalances • Can arise from either respiratory dysfunction or metabolic disturbances • Deviations divided into four general categories – Respiratory acidosis – Respiratory alkalosis – Metabolic acidosis – Metabolic alkalosis
• The kidneys help remove excess chemicals from the blood. It is the kidneys that ultimately remove (from the body) H+ ions and other components of the pH buffers that build up in excess. Acidosis that results from failure of the kidneys to perform this excretory function is known as metabolic acidosis. However, excretion by the kidneys is a relatively slow process, and may take too long to prevent acute acidosis resulting from a sudden decrease in pH (e.g., during exercise). • The lungs provide a faster way to help control the pH of the blood. The increased-breathing response to exercise helps to counteract the pHlowering effects of exercise by removing CO2, a component of the principal pH buffer in the blood. Acidosis that results from failure of the lungs to eliminate CO2 as fast as it is produced is known as respiratory acidosis.
Metabolic Acidosis • Includes all types of acidosis other than those caused by excess CO2 in body fluids • Causes – Severe diarrhea – Diabetes mellitus – Strenuous exercise
• Compensations – Buffers take up extra H+ – Lungs blow off additional H+ generating CO2 – Kidneys excrete more H+ and conserve more HCO3-
Respiratory Acidosis • Result of abnormal CO2 retention arising from hypoventilation • Possible causes – – – – –
Lung disease Depression of respiratory center by drugs or disease Nerve or muscle disorders that reduce respiratory muscle activity Holding breath Airway obstruction
• Compensations – Chemical buffers immediately take up additional H+ – Kidneys are most important in compensating for respiratory acidosis
Metabolic Alkalosis • Reduction in plasma pH caused by relative deficiency of noncarbonic acids • Causes – Vomiting – Ingestion of alkaline drugs • Compensations – Chemical buffer systems immediately liberate H+ – Ventilation is reduced – If condition persists for several days, kidneys conserve H+ and excrete excess HCO3- in the urine
Respiratory Alkalosis • Primarily due to excessive loss of CO2 from body as result of hyperventilation • Possible causes – – – –
Fever Anxiety Aspirin poisoning Physiologic mechanisms at high altitude
• Compensations – Chemical buffer systems liberate H+ – If situation continues a few days, kidneys compensate by conserving H+ and excreting more HCO3-
Patient evaluation The presence of an acid-base disturbance may be suspected on the basis of clinical presentation or by results of laboratory data (eg, a low HCO3-). Evaluation of any acid-base disorder can then be approached in a stepwise manner
ACID-BASE Parameters
Problem? • A patient is found to have an arterial pH of 7.25, a plasma [HCO3-] of 14mM and a pCO2 of 33 mmHg. What acid-base disturbance is present?
Eggs, oily fish
Vit D and the kidney - conversion of Vit D to calcitriol - Enhances Ca2+ absorption - Increases Ca2+ in plasma Renal hydroxylase
