Acid Base Disorders

Acid Base Disorders

Hydrogen ion (H+) homeostasis Essential for life:
e.g. mitochondrial function charge & shape of proteins ionisation of Ca++, Mg++

The concentration H+ ion is 35-45 nmol/L

Hydrogen ion units

H+ conc. as nanomoles per litre (nmol/L) H+ as pH pH = 1/ log10 H+ in mol/L

e.g. 100 nmol/L = 1/ log10 100 x 10-9 pH = 1/log 10-7

pH = 7

In vivo production of protons

The human body is a net-producer of

protons (non-carbonic acids)

Intracellular and extracellular proton

concentration still needs to be kept within

narrow limits

Understanding Normal Acid-Base Handling

Metabolic processes in the body lead to the production of acid

The catabolism of glucose and fatty acids produces CO2 and H2O, effectively carbonic acid.
About

1 mmol/Kg body weight of H+ is produced a day in the body.

Respiratory elimination of CO2 and cellular buffers handle this acid load.

Renal excretion of acid must be maintained.

Daily H+ turnover (mmol/24hrs)

Source of acid
CO2

Production
tissue respiration

Amount
20,000 lungs

Disposal

Lactate
FF/acids

glycolysis
lipolysis

1300
600

gluconeogenesis & oxidation re-esterification & oxidation

oxidation oxidation of amino acids renal excretion & buffered acids

Ketoacids Urea synthesis

ketogenesis ureagenesis

400 1140

H2SO4

S-containing amino acid

40

Sources of Daily acid load

CELL METABOLISM Volatile H+ CO2 Non-volatile H+ abnormal metabolic acids (lactic, acetoacetic, hydroxybutyric, formic,glycolic)

DIET Proteins, acidic or alkali foods Toxins drugs

EXTERNAL FLUID

BLOOD IN CAPILLARIES

Definitions, buffers, equations, pH, pKa Acid- tends to donate a proton

HA H+ + ABase- tends to accept a proton

B + H+
pH -log[H+]

BH+

HA H+ + A[H+][A-] Ka [HA]

[HA]
Rearrange:

[H+] = Ka

[A-]

Taking minus logs: [HA]

-log [H+] = -log [Ka] - log [A-]

pKa -log Ka
and pH = -log[H+]

[HA] -log[H+] = -log[Ka] - log [A-] [A-] pH = pKa + log [HA]

This is the Henderson-Hasselbalch Equation

Use of biological buffers

Needed for buffering of protons produced by the production of CO2 from cells (15,000 mmol/24 h) by catabolism of sulfuric amino acids (100 mmol/24 h) by intermediary metabolism, e.g. lactic acid, acetoacetic acid, beta-hydroxybutyric acid

Common buffer systems in the body

plasma

H+ + HCO3- H2CO3

pKa ~ 6.1

urine

H+ + NH3

NH4 +

pKa = 9.0

urine

H+ + HPO4-- H2PO4-

pKa = 6.8

cell

H+ + protein- proteinH

pKa = 7.0

Buffering
Buffering: Limitation of the change in H+ in the face of a tendency to change

Base- + H+

Hbase

Bicarbonate buffering system most important HBase + OHH2O + BaseHCO3- + H+ H2CO3

H2CO3 + OH-

HCO-3 + H2O

The CO2 - HCO3- buffer system is important in the plasma H+ + HCO3- H2CO3 CO2 + H2O

The pKa = 6.1

pH = 6.1 + log

[HCO3-]
[H2CO3]

Since H2CO3 = pCO2 x (0.03)

pH = 6.1 + log

[HCO3-] [.03 x pCO2]

Other buffers: haemoglobin

CO2 from tissue respiration
CO2
Carbonate

Cl-

Cl-

CO2 + H2O

dehydratase

H2CO3

H+ + HCO-3
Hb-

HCO-3

erythrocyte

HbH

Other buffers: haemoglobin

CO2 loss in alveoli
CO2
Carbonate

Cl-

Cl-

CO2 + H2O

dehydratase

H2CO3

H+ + HCO-3
Hb-

HCO-3

erythrocyte

HbH

Recovery

of Filtered

Bicarbonate in Kidneys

Recovery of Filtered Bicarbonate in Kidneys

Generation of Additional Bicarbonate in Kidneys

 The Kidney
Reabsorbs 4500 mmol of HCO3 per day Generates new HCO3 to replenish buffer stores The Proximal tubule does most of the work The Distal tubule eliminates H+ = to the nonvolatile acid production

Hydrogen ion excretion

Lungs: Kidneys:
rapid and sensitive compensation by controlling CO2 excretion
(only method for direct H+ excretion)

H+ excretion directly and as H2PO42Ammonium excretion (oxoglutarate goes to liver; H+ used for gluconeogenesis)

Liver:

Lactate used for gluconeogenesis Oxoglutarate from kidney used for gluconeogenesis

Simple Acid-Base Disturbances

pH = pK + log10 [HCO3]

(0.030)(paCO2)
pH = 6. 1 + log ( metabolic component) (respiratory component) HCO3 & CO2 &
_

CO2 = HCO3 =
_

pH pH

DISORDERS OF ACID BASE STATUS

RESPIRATORY
ACIDOSIS ALKALOSIS pCO2 pCO2

METABOLIC
ACIDOSIS ALKALOSIS BICARB. BICARB.

Metabolic acidosis

Anion Gap
A mathematical concept (Na+ + K+ ) - ( Cl- + HCO3-) < 7-17 mmol/L The gap consists of other ions, mainly Ca2+, Mg+, PO42-, sulfate-, organic anions (e.g. lactate, acetoacetate) The sum of anion and cation in plasma must be the same (electroneutrality) Overproduction of e.g. lactate will increase the anion gap, indicating that the concomitant acidosis is of the metabolic type as will decreased excretion of acid anions as in renal failure. Therefore an increased anion gap is a useful marker of metabolic acidosis

Evaluating a low serum HCO3 A low serum HCO3- can be due to:
Metabolic acidosis
High anion gap acidosis Hyperchloremic acidosis

Respiratory alkalosis

 High anion gap: MUDPILES

Methanol Uremia Diabetic ketoacidosis Paraldehyde Isopropyl alcohol Lactic acidosis Ethylene glycol Salicylates

Classification of Metabolic Acidosis

Compensatory Response
In simple metabolic acidosis the high [H+] stimulates respiration resulting in a compensatory fall in the PCO2 (secondary respiratory alkalosis) which brings the [H+] back towards, but never to, normal.
(1) Maximum compensation occurs in 12-24 hours (2) For a given [HCO3] the final PCO2 level can be calculated from: PCO2 = 1.5 x [HCO3] + 8 (+/- 2) (3) The limit of compensation is a PCO2 of about 10 mmHg

Metabolic alkalosis
Loss of Hydrogen Ions Vomiting Ingestion of Alkali Potassium Deficiency

Metabolic alkalosis

Metabolic Alkalosis
Saline Responsive (ECV contraction, Urine [Cl] <20 mmol/L) Gastrointestinal -Vomiting, Gastric suction, Chloride diarrhoea Renal -Diuretic therapy Exogenous alkali -Bicarbonate (IV, oral), Antacids (eg Mg carbonate) Organic acid salts (eg, lactate, citrate, acetate) Saline Unresponsive (ECV expansion, Urine [Cl] >20 mmol/L) Mineralocorticoid excess Primary hyperaldosteronism, Cortisol & Mineralocorticoid excess Cushing's syndrome

Metabolic Alkalosis: pathophysiology

Pathophysiology: The development of a metabolic alkalosis requires two simultaneous processes: bicarbonate generation, & plasma bicarbonate maintenance

(1) Generation of bicarbonate:

Loss of H+:
Gut, Renal, Exogenous HCO3 The normal kidney responds to a high plasma [HCO3] by increasing urinary excretion of the ion. This is a very efficient process and for the development of a metabolic alkalosis a second mechanism to maintain the high plasma [HCO3] is required: the maintenance mechanism.

Metabolic Alkalosis: pathophysiology (Cont'd)

Maintenance of high plasma bicarbonate:

This is carried out by the kidney (renal bicarbonate retention) and occurs in the following situations:
Volume depletion Potassium depletion

Hypercapnia
Thus when evaluating the subject with metabolic alkalosis attention should be given to the possible causes of generation and of maintenance. From a management point of view metabolic alkalosis can be classified as either saline responsive or saline unresponsive

Metabolic Alkalosis: pathophysiology (Cont'd)

Response to IV saline therapy

The response of the subject with metabolic alkalosis to a saline (NaCl) infusion provides a further classification of the disorder.

Saline responsive metabolic alkalosis

If the patient is hypovolaemia (dehydrated) a saline infusion will resolve the disorder, ie remove the maintenance process and allow bicarbonate to be excreted by the kidney; hence "saline responsive"

Saline unresponsive metabolic alkalosis

If the patient is euvolaemic, eg the metabolic alkalosis of mineralocorticvoid excess, a saline infusion will not alleviate the condition: hence "saline unresponsive".

Compensation
The compensatory process is decreased respiratory exchange and high pCO2 Response reaches its maximum in 12-24 h pCO2~ 60 mmHg. For each 1mmol/L rise of HCO3-, pCO2 should increase by 0.7 mmHg Expected pCO2 mm Hg: 0.9 X (HCO3-) + 9

Respiratory disorders

Compensation by increase in HCO3

In the acute phase there is a rise of 2-4 mmol/L of HCO3 Will result in plasma level 28-30mmol/L In the chronic phase there is a slow, consistent increase in the HCO3 due to renal generation reaches maximum in 2-4 days The maximum level is 45 mmol/L (HCO3) mmol/L = 0.44 X pCO2 +7.6

Compensatory response
Secondary metabolic acidosis HCO3 level will decrease Acute: HCO3 will decrease upto 18mmol/L Chronic:HCO3 will decrease upto 12 mmol/L Resp.alkalosis; Can be completely compensated. pH will be normal