ACID BASE BALANCE

12/2020
Importance pH regulation in the body
 Acid base balance is an important aspect in medicine.
 pH of the intra and extra cellular fluid should be maintained within normal limit.
 Changes in blood pH will cause changes in intracellular pH and may alter cellular metabolism.
 Since most of the structural and functional molecules like transporters, enzymes, receptors are
proteins in nature and pH changes may affect many metabolic processes.
 Because changes in pH alter the ionization state of protein molecules, consequently that of the
activity of these proteins
 Most of the metabolic reactions in the body are enzyme- catalyzed reactions. These enzyme-
catalyzed reactions can reach to maximal velocity only at their optimal pH.
 Cell division, apoptosis, signaling process and membrane transport processes are pH
dependent.
 There is also close association between acid-base balance and electrolyte balance.
 Changes in pH together with pCO2 affect the affinity of Hb with O2 and tissue oxygenation.
 Decrease in pH increases sympathetic tone and may lead to cardiac dysrhythmias.
 Therefore, pH of ICF and ECF must be kept within normal limit for proper metabolism and
survival of the cells.
 Understanding of both theoretical and practical aspects of acid base balance is vital to patient
care in clinical practice.

Acid is proton donor i.e., anything which dissociates into one or more protons
HA H+ + A
Strong – dissociate completely e.g., HCl
Weak – dissociate incompletely e.g, H2CO3

Base is proton acceptor i.e., anything which can combine with protons to form a conjugate base
e.g., NH3 + H+ = NH4+

pH
Acidity is determined by the concentration of free hydrogen ions (protons), which is expressed in
terms of pH.
pH = -log [H+]
pH of different organs and tissues may vary due to difference in metabolic activity.

A buffer is a substance that has an ability to bind or release H+ in a given solution thus
maintaining the pH relatively constant despite the addition of considerable quantity of acid and
base.
A buffer contains weak acid or weak base and its conjugated salt.

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Buffering capacity may be defined as the amount of acid or base that can be added to a buffer
solution or taken from it, before a significant pH change is affected. It depends on its
concentration and its pKa value.
In Henderson- Hasselbalch equation,
pH = pKa + log [A- ]
[HA] pKa = dissociation constant of acid which is half ionized

When [A-] = [HA], log [A- ] /[HA] = 0  pK= pH

This is why the most effective buffers in the body would be expected to be those with pK close to
pH in which they operate.

pH [H+]
Arterial 7.4 ± 0.05 (7.35 ± 7.45) 40 nmol/L
ISF < 7.4
ICF 7.0 100 nmol/L
RBC 7.2
Acidosis < 7.35 >45nmol/L
Alkalosis >7.45 < 35nmol/L
Compatible with life 6.8 -7.7
Limiting pH in urine 4.5
Skeletl muscle 6
Normal anion gap 10 - 14 mEq /L

Sources of H+ in the body

1. Physiologic condition - Products of metabolism
 Metabolism generates carbon dioxide within cells. Carbon dioxide dissolves in water,
forming carbonic acid, which in turn dissociates hydrogen ions and HCO3-
Carbonic anhydrase
CO2 + H2O H2CO3 H+ + HCO3-
 Metabolism also generates other inorganic acids such as sulphuric acid from
metabolism of sulphur containing amino acids (cysteine, methionine), phosphoric acids
from metabolism of nucleic acid, phospholipids and phosphoprotein.
 During strenuous exercise, aerobic exercise produces more CO2 and anaerobic exercise
produces lactic acid
 Prolong fasting and starvation produce ketoacids such as acetoacetate and β hydroxy
butyrate
2. Pathological condition
 uncontrolled diabetic mellitus produce ketoacids - acetoacetic acid & β –OH butyric
acid
 Retention of CO2 as a result of hypoventilation seen in some respiratory diseases
 Retention of H+ as a result of kidney disease
 Relative excess of H+ due to loss of HCO3- from lower part of GIT e.g. diarrhea, fistula
3. Ingestion of acidifying salts like NH4Cl
NH4Cl + H2O  NH4OH + HCl

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Sources of alkali
 The body does not produce as much alkali as acids. Most of it comes from exogenous sources.
1. Dietary source: fruits and vegetables contain salts of weak organic acids such as NaHCO3
and KHCO3
2. Pathological condition
a. Increase CO2 wash out due to hyperventilation
b. Relative excess of alkali due to loss of acid e.g., excessive vomiting
3. Ingestion of alkalinizing salts: antacids like sodamint, NaHCO3

Overview of regulation of acid – base balance

It involves buffer system, lungs, kidneys and erythrocytes contribute to the maintenance of
the acid-base balance
 Buffers maintain pH relatively constant by converting strong acids/base to weak acids/bases.
(more or less immediate, within second) – 1st line of defense against pH imbalance
 Lungs – control the exchange of carbon dioxide and oxygen between blood and atmospheric
air(within minutes)
 Erythrocyte transport gases between lungs and tissues.
 Kidneys control plasma bicarbonate concentration and excretion of H+-(within hours to days)
These systems operate simultaneously. Buffers can respond within seconds to addition of acid or
base (1st line of defense). But, they do not serve to eliminate the acid from the body or unable to
replenish the alkali reserve of the body.
 Metabolism generates substantial quantities of inorganic acids as well as organic acids.
 Volatile acids are derived from CO2 and can be removed through lungs (H2CO3)
 Non-volatile acids are derived from other than CO2 and can’t be excreted through lungs but
from kidneys.

% distribution pKa
Bicarbonate 75% 6.1 Most important blood
buffer
Protein 20% 6 – 7 (Histidine imidazole group ) Intracellular buffer
Phosphate 5% 6.8 Mainly in urine, ICF, bone
Of buffer OxyHb = 6.68
capacity DeoxyHb = 7.93

Buffers systems of the body fluid

1. Blood buffer
a. Buffers in plasma HCO3- , HPO42-, Protein-, organic acid anion
H2CO3 H2PO4- HProtein organic acid
b. Buffers in red cells HCO3- , HPO42-, Hb - , HbO2- , organic acid anion
H2CO3 H2PO4- HHb HHbO2 organic acid
2. Interstitial fluid same as plasma except lower protein concentration
3. Intracellular fluid same as RBC except no hemoglobin
Phosphates & protein buffer system are more prominent

According to cellular compartment,

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 A. Major ECF buffer – bicarbonate buffer
B. Major ICF buffer – proteins and phosphate buffer

Bicarbonate Buffer System

 It consists of HCO3-/ H2CO3
 It takes 75% of buffering capacity.
 This is open buffer which remain at equilibrium with atmospheric air. Buffering capacity of
bicarbonate buffer exceeds all the closed buffer system
 This system is the most important buffer in ECF despite of its pKa 6.1
According to Henderson- Hassel Balch equation,
[ HCO3- ]
pH = pKa + log
[H2CO3]
[ HCO3-]
pH = pKa + log
[Pco2 х solubility coefficient of CO2]
pH = pKa + log 24
40 х 0.03
= pKa + log 24/1.2
= pKa + log 20/1
= 6.1 + 1.3
= 7.4
 This equation demonstrate that blood pH is determined by the ratio of bicarbonate
concentration and dissolved CO2 concentration.
 At physiologic pH 7.4, the ratio of HCO3- to H2CO3 is 20:1 which ensure high buffering
efficiency against acid produced by body.
 When H+ concentration increases, H+ is immediately buffered by HCO3- to form weak acid
H2CO3. Carbonic anhydrase
+ -
H + HCO3 H2CO3 H2O +CO2
 The H has been neutralized and the resultant CO2 is eliminated through the lungs, attempting
+

to normalize [ HCO3-] / pCO2 ratio.

 On the other hand, when H+ concentration decreases, the carbonic acid component of the
buffer will give off H+ for a reaction.
Carbonic anhydrase

 H2O +CO2 H2CO3 H+ + HCO3-

 As more CO2 are used up for generation of H2CO3, pCO2 is decreased. Subsequently,
ventilation rate will decrease, retaining CO2 and attempting to normalize [ HCO3-] / pCO2
ratio.
 Since pCO2 concentration is controlled by the lungs, it is called respiratory component of
the acid base balance.
 Since plasma HCO3- concentration is controlled by kidneys and RBCs, it is called metabolic
component of the acid base balance.
 Therefore,bicarbonate buffer system is said to be open buffer system since the amount of
dissolved CO2 can be regulated by the lungs and the plasma concentration of HCO3- can be
regulated by the kidneys and RBC.
Protein Buffer system

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 Protein-
H protein
 Protein buffer is an effective buffer system in the body because of high concentration and their
amphoteric property, possessing two functional groups (H+ accepting amino group and H+
donating carboxyl group)
 Albumin is the most abundant plasma protein and does contribute significantly.
 Even a single amino acid can act as buffer because of their amphoteric property.
 In alkaline pH, the amino acid is in anionic state RCOOH  RCOO- + H+
 In acidic pH, the α amino group is protonated and yields cation, RNH2 + H+  RNH3+
 At pH value of blood, the acidic amino acids (Asp, Glu) and histidine are effective.
 The most effective group is histidine imidazole group with a pK value of 6.0 -7.0. It is near to
pH 7.4 to be of physiologically significant as buffer.

Hemoglobin Buffer system

Deoxyhemoglobin Oxyhemoglobin
Hb- HbO2-
H Hb H HbO2
 Hemoglobin has 6 times buffering capacity than plasma protein.
 Because of presence of 4 α amino terminal ends and 4 carboxyl terminal ends, presence of 38
histidine residues per tetramer. The imidazole side chain of histidine can accept or donate H +
most effectively.
 In addition, hemoglobin has high concentration about 14-15 g/dl in blood compared to plasma
protein (4.9 – 8.4g/dl).
 Oxyhemoglobin (pK - 6.68) is stronger acid than deoxy hemoglobin (pK -7.93). The weaker
acid deoxy Hb is a better buffer than oxyHb.
Phosphate Buffer System
 It consists of HPO4=/ H2 PO4- pair.
 Dihydrogen phosphate (H2PO4-) act as weak acid while monohydrogen phosphate (HPO4=) is
the conjugate weak base.
 In the plasma, the phosphate concentration is too low to be a quantitatively important buffer.
 It is an important intracellular buffer because of high intracellular concentration and its pKa of
6.8 is close to physiological pH.
 It also plays a role in renal handling of H+.
Organic acid anions
 They are lactate/lactic acid, pyruvate/pyruvic acid, acetoacetate/acetoacetic acid.
 But their pH ranges are too low to contribute significantly as blood buffer.
Buffers can respond immediately to addition of acid or base, but they do not serve to
eliminate the acid from the body. They are also unable to replenish the alkali reserve of the
body.

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Handling of CO2 by RBC
 The 70% of CO2 entering RBC is hydrated into weak acid H2CO3 by the action of carbonic
anhydrase. H2CO3 dissociates to H+ and HCO3-(fixed form)
 This reaction in plasma is non enzymatic and proceeds slowly, generating only minute
amounts of carbonic acid.
 The generated H+ is buffered by Hb. HCO3- produced moves to plasma in exchange for
chloride ion (chloride shift).
 20% of CO2 is carried by Hb as carbamino groups.
 At the lung side, because of higher pO2, Hb releases the H+. H+ reacts with HCO3- and forms
H2CO3 which in turn release CO2.

Respiratory adjustment by hyperventilation in acidosis

 Respiratory rate is controlled by respiratory center located in brain stem. Respiratory center
has chemoreceptors sensitive to pCO2 and pH.
 Role of respiratory system in acid base regulation is mediated through elimination of CO 2 in
metabolic acidosis or retention of CO2 in metabolic alkalosis.
 Respiratory adjustment is the second line of defense and occur within 1-3 minutes
 But it cannot continue for long. Thus, it is very important over brief periods.

Respiratory adjustment by hypoventilation in acidosis

Acid H+ + HCO3- H2CO3 H2O + CO2 (dissolve form)
Carbonic anhydrase

Stimulation of chemoreceptors
(central & peripheral)

Stimulation of respiratory center

Increase respiration rate and ↑CO2 washout,

so pCO2 falls and pH returns back to normal

Respiratory adjustment by hypoventilation in alkalosis

Strong base NaOH + H2CO3 NaHCO3 + H2O
Carbonic anhydrase

H2O + CO2

pCO2 fall inhibit respiratory center decrease respiration rate and CO2
retention ,so pCO2 will rise again and pH returns back to normal

Regulation of pH by kidneys
 The kidneys play an essential role in conservation of [HCO3-] and excretion of H+. pH of urine
may vary from 4.5 to 9.8 depending on amount of H+ secreted.
 The major kidney mechanisms for regulation of pH are:

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 1. excretion of H+
2. Conservation of HCO3-

Handling of H+ and HCO3- by kidneys

At proximal tubule,
 H+ is secreted into lumen by Na+ – H+ exchanger. The entered Na+ is transported to ISF by
Na+- K+ ATPase.
 Most of the secreted H+ bind with filtered HCO3- and forms H2CO3. By the action of carbonic
anhydrase, it is converted to water and CO2 which diffuses into the renal tubular cells. . In the
cells, CO2 is reconverted into H2CO3 which dissociates again to H+ and HCO3-.
 HCO3- is returned back to plasma by Na+ - HCO3- transporter or Cl- - HCO3- exchanger.
 By this way, PCT can reabsorb almost all of the filtered HCO3- whereas H+ is secreted into
lumen. Most of the secreted H+ bind with HCO3- and are used in reabsorption of HCO3-.
 In PCT, H+ secretion is necessary for the reabsorption of filtered bicarbonate.
 Therefore, there is no net excretion of H+ in PCT.
At distal tubules and collecting ducts
 New bicarbonate generation and excretion of H+ take place
 Blood with increased pCO2 reach the renal tubular cells. So CO2 diffuse into the cells and
hydrated to form H2CO3 by carbonic anhydrase.
 Then, H2CO3 is dissociated into H+ and HCO3-.
 HCO3- is returned back to plasma by Cl- - HCO3- exchanger whereas H+ is excreted into lumen.
 At the distal tubules and collecting ducts, H+ secretion is by ATP driven H+ pump/ Na+/K+ – H+
exchanger.
 H+ in the distal tubular lumen is buffered by phosphate ion and by ammonia. Then, they are
subsequently excreted in the urine.

Fate of H+ in the urine

 Normal urine is acidic. Maximal H+ secretion depends on tubular fluid pH.
 The limiting pH of tubular fluid is about 4.5 at which H+ secretion stops.
 If free H+ in tubular fluid are not buffered, limiting pH would be rapidly reached and H+
secretion will stop.
 Three important reactions in the tubular fluid remove free H+ permitting more acids to be
secreted.
 These are reaction
1. with HCO3 - to form CO2 and H2O in PCT
2. with NH3 to form NH4+ in both PCT and DCT.
3. with HPO4= to form H2PO4- in DCT and CD
 In the proximal tubule, most of the secreted H+ reacts with HCO3- to form H2CO3 which breaks
down to form CO2 and H2O by carbonic anhydrase in the brush border of the cells. CO2 enter
the tubular cells by diffusion and form H2CO3. One mole of HCO3- is diffused from tubular
cells into the blood.
 In the distal tubules and collecting ducts, secreted H+ also reacts with dibasic phosphate
(HPO4=) to from monobasic phosphate (H2PO4-).
 In the proximal and distal tubules, H+ combines with NH3 to form NH4+ which cannot diffuse
back into tubular cells and are excreted in urine.

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 About half to two thirds of the body acid load is eliminated as NH4+, a major urine acid.
Ammonium ion excretion increases in acidosis.
Ammonia production in kidneys
In renal tubular cells,
glutaminase glutamate dehydrogenase
Glutamine glutamate α – ketoglutarate
NH3 NH3
 Ammonia diffuses through the luminal membrane. Then, H+ is trapped inside the tubular
lumen as ammonium ion (NH4+) to which membrane is impermeable and are excreted in the
urine
 glutaminase activity is increased in acidosis and large amount of NH4+ excretion occur in
acidosis.
Clinical significance
 Defect in renal handling of HCO3- and H+ lead to renal tubular acidosis (RTA). Proximal RTA
is due to impaired HCO3- reabsorption. Distal RTA is due to impairment of H+ secretion by
distal tubular cells.

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 Disorders of acid – base balance
Acidosis is a process that leads to the accumulation of hydrogen ion.
Alkalosis is a process that leads to the decrease of hydrogen ion concentration in plasma.
Acidosis > common alkalosis
Classification depending on primary cause
a. Metabolic acidosis
b. Respiratory acidosis
c. Metabolic alkalosis
d. Respiratory alkalosis
Metabolic disorders are caused by a direct alteration in bicarbonate concentration. Respiratory
disturbances are due to a change in carbonic acid level. In actual clinical situation, mixed type of
disorders are common.
Disturbances pH & [H+] HCO3- PCO2
Acidosis Metabolic <7.35, >45nmol/L ↓ Normal or ↓
Respiratory Normal or ↑ ↑
Alkalosis Metabolic >7.45, <35nmol/L ↑ Normal or ↑
Respiratory Normal or ↓ ↓

METABOLIC ACIDOSIS
In metabolic acidosis, plasma bicarbonate concentration is less than normal range and
blood pH is less than 7.35.
Causes:
1. Excessive production of H+ or ingestion of acid
1) Acetoacetic acid and β– hydroxybutyric acids in diabetic ketoacidosis and in starvation.
2) Sulphuric acid from metabolism of the sulphur- containing amino acids (methionine,
cysteine)
3) Phosphoric acid from increase breakdown of endogenous nucleic acid, phospholipids
4) Lactic acidosis may result from severe exercise and any pathological cause of tissue
hypoxia.(shock)
5) Transfusion of large quantity of banked blood.
6) Ingestion of drugs such as aspirin.
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 7) Ingestion of acidifying salts such as ammonium chloride.
2. Failure to excrete H+
a) renal failure
b) inhibition of carbonic anhydrase activity (e.g. carbonic anhydrase inhibitors such as
acetazolamide)
c) Hypoaldosteronism
The H+ / Na+ exchange active transport mechanism is stimulated by aldosterone. If
there is a lack of aldosterone due to adrenocortical insufficiency( as in Addison’s disease),
or in the presence of an aldosterone antagonist such as spironolactone, H+ excretion will be
impaired. Hence, metabolic acidosis is produced.
3. Direct loss of base
Pancreatic, biliary and jejunal secretions are distinctly alkaline, having a much greater
bicarbonate concentration than in plasma. Therefore loss of these secretions in diarrhea or
fistula cause a direct loss of buffer base (HCO3-), resulting in metabolic acidosis.

Compensation
 Buffers plays immediately to restore normal pH. The major buffers in the plasma are
bicarbonate buffers and contribute 75% of ECF buffering capacity.
 The body response is to keep the [HCO3-] / pCO2 ratio normal. This is done by reducing pCO2.
Reduction of pCO2 can be done by increasing ventilation.

Acid H+ + HCO3- H2CO3 H2O + CO2 (dissolve form)

carbonic anhydrase

H+ pH Stimulation of chemoreceptors
(central & peripheral)

Stimulation of respiratory center

↑ CO2 washout
 The pCO2 falls and this would attempt to restore the [HCO3-] / pCO2 ratio towards 20:1
(partial compensation)
 Renal compensation sets in hours to days. Increased excretion of H+ and conservation of
HCO3- occurs.(refers to renal handling of H+ and HCO3-)

ANION GAP
In plasma, the number of electrical charges on the cations equal with the number of
charges on the anions. However, in the routine laboratory, only Na+, K+, Cl- and HCO3- are
measured.
The difference between the sum of concentration of the cations and the sum of
concentration of anion is called anion gap.
Anion gap represents usually unmeasured anions normally present in plasma such as
SO4 , PO42-, lactate, 3 OH butyrate and acetoacetate.
2-

[Na+] + [K+] = [Cl-] + [HCO3-] + [A-]

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 [A-] = {[Na+] +[K+]} – {[Cl-] + [HCO3-]}
[A-] = (135 + 3.5) – (103+24)
[A-] = 11.5 mEq/L
Normal value: 10-14 Eq/L

Anion gap is useful to classify the types of metabolic acidosis.

I. Normal anion gap metabolic acidosis
When there is loss of both anions and cations, the anion gap is normal, but acidosis may
exist. E.g; in diarrhea, hyperchloraemic acidosis(in renal tubular acidosis and acetazolamide
therapy, pancreatic fistula)
II. Increased anion gap metabolic acidosis
 Renal failure
 Ketoacidosis
 Lactic acidosis
 Ingestion of some toxin
Renal failure causes increased anion gap acidosis by decreased acid excretion and
decreased HCO3− reabsorption. Accumulation of sulfates, phosphates and urate accounts for
the increased anion gap. There is no change in chloride level.
Ketoacidosis is a common complication of type 1 diabetes mellitus but it also occurs
with chronic alcoholism and prolonged fasting.
Lactic acidosis is the most common cause of metabolic acidosis in hospitalized
patients. Lactate accumulation results from a combination of excess formation and decreased
metabolism of lactate. Excess lactate production occurs during states of anaerobic metabolism.
The most serious form occurs during the various types of shock. Diseases (heart failure,
sepsis) and some drugs(propofol) can cause lactic acidosis. This unmeasurable anion may be
increased up to measurable quantities in severe lactic acidosis
Ingestion of some toxin (ethanol, methanol, salicylate, ethylene glycol) also cause
increased anion gap acidosis.

[Symptoms and signs

Mild acidemia is itself asymptomatic. More severe acidemia (pH < 7.10) may cause
nausea, vomiting, and malaise. Symptoms may occur at higher pH if acidosis develops rapidly.
The most characteristic sign is hyperpnea (long, deep breaths at a normal rate), reflecting a
compensatory increase in alveolar ventilation; this hyperpnea is not accompanied by a feeling of
dyspnea.
Severe, acute acidemia predisposes to cardiac dysfunction with hypotension and shock,
ventricular arrhythmias, and coma. Chronic acidemia causes bone demineralization disorders (eg,
rickets, osteomalacia, osteopenia).]

Metabolic alkalosis

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 Metabolic alkalosis is present when there is loss of acid other than H2CO3 from the ECF,
or an increase in base. pH is >7.45 and HCO3- concentration is above the normal range
Causes:
1. A loss of acid occurs when there is vomiting (loss of HCl of gastric juice) as in pyloric stenosis.
2. A gain in base occurs when absorbable alkalis such as NaHCO3 are given in excess.
3. Movement of H+ in the cells – seen in hypokalemia.
Compensation
 In response to increase pH and reduction of H+, buffers play immediately to restore normal pH.
 ↑pH is sensed by central and peripheral chemoreceptors that cause reduction in rate of
ventilation. Finally, retention of CO2 and PCO2 rises and this would attempt to restore the
[HCO3-] / pCO2 ratio towards 20:1
 This mechanism occur rapidly after the onset of metabolic alkalosis.

Respiratory acidosis
 Respiratory acidosis (hypercapnia) is defined by arterial PCO2 > about 45mmHg (6.0 kPa)
and pH< 7.35.
 Causes of respiratory acidosis
a) Defective ventilation
 Depression of the respiratory center(cerebral injury, tumors, lesion of spinal cord and
drugs such as general anesthesia and all sedatives like morphine, barbituates)
 Mechanical defects(Crushed chest, pneumothorax, haemothorax, neuromuscular
disease of respiratory muscles)
b) Defective diffusion
 Pneumonia
 Pulmonary edema
 Pulmonary fibrosis
c) Defective perfusion
 Pulmonary infarction or embolism
 General destruction of lung tissue and compression of vessels by tumors

Compensation in acute respiratory acidosis

 The increased arterial pCO2 causes the following mechanism
CO2 + H2O → H2CO3 → H+ + HCO3-
 This reaction occur rapidly in the RBC because of presence of carbonic anhydrase. The
resultant HCO3- enter into plasma in exchange with Cl-. Therefore, plasma HCO3- rises in
acute condition.
 1mmol/L of HCO3- rise for every 10 mmHg rise of pCO2 above its reference value of
40mmHg
 99% of buffering mechanism occur intracellulariy. The H+ is buffered by proteins
(including Hb) and phosphates.
 In acute acidosis, increased plasma HCO3- is not due to renal regulation but due to
regulatory mechanism in RBC.
In summary, compensation of acute respiratory acidosis is done by intracellular
proteins and phosphate buffers and plasma bicarbonate level rises slightly. HCO3-
buffer system does not contribute in this compensation
Compensation in chronic respiratory acidosis

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  In chronic respiratory acidosis, plasma HCO3- level rises due to renal retention of HCO3-.
 In chronic respiratory acidosis, there are two mechanisms to elevate plasma HCO 3-
 The first mechanism is the same as compensation mechanism in acute respiratory
acidosis.
CO2 + H2O → H2CO3 → H+ + HCO3-
 This reaction occur rapidly in the RBC b/c of presence of carbonic anhydrase. The
resultant HCO3- enter into plasma in exchange with Cl-. Therefore, plasma HCO3- rises
 The second mechanism is to increase secretion of H+ from renal tubules. This results in
1) increased HCO3- reabsorption
2) increased Na+ reabsorption in exchange for H+
3) increased NH3 production in the tubular lumen and NH4+ excretion in the
urine
 4mmol/L of HCO3- rises for every 10 mmHg rise in pCO2 above its reference value of
40mmHg
 The renal response occur by 6 to 12 hours with a maximal effect reached by 3 to 4 days.
 pH is returned towards normal much more than that occurs in acute respiratory acidosis.

Respiratory alkalosis
Respiratory alkalosis or hypocapnia is defined by PCO2 in arterial blood less than 35mmHg
(4.6kPa) and pH more than 7.45

Causes:
 Hyperventilation during exercise
 Anxiety
 Fever
 Pregnancy( due to progesterone)
 Hysteria (voluntary hyperventilation)
 Drugs (aspirin and antidepressant)

Compensation in acute respiratory alkalosis

 Decreased arterial pCO2 cause reduction of H+ in blood. H+ in the cells move out to ECF,
where they combine with HCO3- to form H2CO3
H+ + HCO3-→ H2CO3
 The H+ are primarily derived from intracellular buffers such as Hb, protein and phosphates.
 This reaction leads to mild reduction in plasma HCO3-
Compensation in chronic respiratory alkalosis
 If respiratory alkalosis persists for longer than 2-6 hours, renal regulation sets in.
1) reduced H+ secretion
2) reduced excretion of titratable acids (H2PO4-)
3) reduced excretion of NH4+
4) increased excretion of HCO3- due to reduced reabsorption of filtered HCO3-
 New steady state is achieved after 2-3 days.
 Compensatory mechanism in chronic condition offers much better protection of arterial pH
than that of acute condition.

PCO2 = 35- 45 mmHg Cause

Respiratory acidosis > 45mmHg (6kPa) (hypercapnia) Hypoventilation
Respiratory 13
< 35 mmHg ( 4.6 kPa) (hypocapnia) Hyperventilation
alkalosis
Relationship of acid-base disorder and plasma potassium
The H+ entering into the cell is exchanged with K+ to maintain electrical neutrality. It may
result in an increase K+ in plasma (hyperkalemia). Potassium level decrease inside the cells.
Conversely, when HCO3- excess in plasma, it would be buffered by cell derived H+. The
cellular H+ entering into plasma is exchanged with serum potassium. Hypokalemia in plasma and
increased K+ inside cells.
Renal handling of potassium
 In kidney, about 90% of filtered potassium is reabsorbed in loop in Henle. In distal tubule,
K+ is secreted into the lumen and is linked to reabsorption of sodium. At this site, Na+ is
reabsorbed in exchange also for H+ and there is competing between K+ and H+ for the same
transport system.
 In acidosis, the more H+ is pumped into the lumen in exchange for Na+. So, K+ secretion into
the lumen will be limited. This process contributes to hyperkalemia in acidosis.
 Conversely in alkalosis, less H+ is being secreted, more K+ enter into lumen. This leads to
hypokalemia in alkalosis.

Hyperkalemia
Hyperkalemia is a dangerous and life threatening metabolic emergency. It may be due to
I. Gain in total body potassium
1. Intrinsic renal disease
2. Excessive potassium intake
3. Drugs that limit potassium secretion in the distal tubules(spironolactone)
4. Primary aldosterone deficiency (rarely)
II. Rapid shift of potassium out of the cells
1. In exchange for hydrogen ion in severe acidosis
2. Secondary to massive cell damage (crush injury or massive hemolysis, tumor lysis
syndrome)

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