Acidosis and Alkalosis

Disturbances of Acid Base balance

• Acid base disorders are of two categories
Respiratory
Primary defect is in ventilation affecting Pco 2

Metabolic
The defects include production of fixed acids
in excess of kidneys ability to excrete them, or
loss of H from the body, or loss or retention of
+

HCO 3 -

Each of these is subdivided into two

Acidosis (decreased pH due to acidemia)
Alkalosis (increased pH due to alkalemia)
 Disturbances of Acid Base balance
The disorders are best understood from the basis
of Carbonic anhydrase (CA) catalysed reaction
CA CA

• CO + H O
2 2 H CO
2 3 H + HCO
+ 3
-

• H CO is source of H ions in the body

2 3
+

• Normal ratio of base (HCO ) to acid (H CO ) is

3
- 2 3

20:1 at physiological pH of 7.4

• Deviations from this ratio are used to identify

Acid-Base imbalances
Principles of Acid-Base Disorders

 Metabolic acid-base disorders and

alter [HCO3 -]
 secondary metabolic compensation

 Respiratory acid-base disorders and

alter (PCO2 )
 secondary respiratory compensation

4
 Reference ranges and points
Parameters Reference range Reference
point
Na+ 135-147 mmol/L
K+ 3.5-5.0 mmol/L
Cl- 95-105 mmol/L
CO2, total 24-30 mmol/L
pH 7.35-7.45 7.40
PCO2 33-44 mm Hg 40 mm Hg
PO2 75-105 mm Hg
HCO3- 22-28 mmol/L 24 (27) mEq/L
Anion gap 8-16 mEq/L 12 mEq/L
 Acidosis and Alkalosis
• Acidosis: disease process that lowers
HCO 3 - o r raises PCO 2 in the blo o d
resulting in a decrease pH < 7.35

• Alkalosis: disease process that raises

HCO 3 - or lowers PCO 2 in the blood
resulting in an increase pH > 7.45

NB: presence of each, suggest an underlying metabolic

abnormality 6
 ACIDOSIS
decreased failure of metabolic production absorption of prolonged
removal of kidneys to acid of keto acids metabolic acids diarrhea
CO2 from excrete from GI tract
lungs acids

accumulation accumulation excessive loss

of CO 2 in blood of acid in blood of NaHCO 3
from blood

vomiting
from
GI tract
respiratory metabolic
increase in
acidosis plasma H+ acidosis
concentration kidney
disease
(uremia)
depression of
CNS 7
 ALKALOSIS
anxiety overdose high prolonged ingestion of excess
of certain altitudes vomiting excessive aldosterone
drugs alkaline drugs

hyperventilation loss of acid accumulation

loss of CO
reduced CO22 and
and of base
H22CO
H CO32 in
from
the
blood

respiratory metabolic
alkalosis alkalosis
decrease
in plasma H+
concentration

hyperexcitability
of CNS
8
 Metabolic Acidosis
• HCO3- excretion is controlled by the kidney
• One H+ buffers one HCO3-

– So, metabolic acidosis always characterized

by increased production of H+ ions and a
reduction in plasma HCO3-

• Gain of H+
Decrease in pH
• Loss of HCO3-
Causes of metabolic acidosis due to gain of acid
 Endogenous hydrogen ion production:
 Ketoacidosis
 Starvation or as a result of diabetes mellitus

Beta oxidation

Acetyl CoA TCA

Cycle

Acetoacetyl CoA

Acetoacetate

Ketone bodies

β- Acetone
hydroxybutyrate
 Conditions where ketone bodies are
overproduced
• Starvation and diabetes mellitus lead to
overproduction of ketone bodies, with
several complications
• Du rin g s tarv ation , glu con eogen es is
depletes citric acid cycle intermediates,
div er ting acetyl-CoA to ketone body
production
• In diabetes mellitus, when insulin level is
insuf fic ient, extrahepatic tissues cannot
take up glucose ef ficiently from the blood,
either for fuel or for conversion to fat.
 Conditions where ketone bodies are
overproduced
• Under these conditions, levels of malonyl-CoA fall,
relieving the inhibition of carnitine acyltransferase I,
and fatty acids enter mitochondria to be degraded
to acetyl-CoA—which cannot pass through the citric
acid cycle because cycle intermediates have been
drawn off for use as substrates in gluconeogenesis.

• Accumulation of acetyl-CoA leads to overproduction

of t he ket one bodies (acet oacet at e and B-
hyd r o x yb ut yra t e ) , w hic h c a nno t b e use d b y
extrahepatic tissues as fast as they are made in the
liver
• aceton e, wh ich resu lts from th e spon tan eou s
decarboxylation of acetoacetate
 Ketoacidosis
• Higher than normal quantities of ketone bodies
present in the blood or urine constitute ketonemia
(hyperketonemia) or ketonuria, respectively. The
overall condition is called ketosis.

• Ketone bodies are carboxylic acids, which ionize

to release protons. In diabetes mellitus, the acid
level can overwhelm the capacity of the
bicarbonate buffer system and produce a lowering
of blood pH called acidosis, or in combination
with ketosis, ketoacidosis, a potentially life-
threatening condition
Ketoacidosis
Ketoacidosis
 Lactic Acidosis
 When animal tissues cannot be supplied with
sufficient oxygen to support oxidation of the pyruvate
and NADH produced in glycolysis, NAD+ is
regenerated from NADH by the reduction of pyruvate
to lactate
 Lactic Acidosis
Lactic acidosis is characterized by a
bui l dup o f L a cta te i n the bo dy, wi th
consequent generation of low pH in the
blood
Glucose

Pyruvate
NAD
LDH
H
NAD+

Lactate

• salicylate overdose
 Other causes of metabolic acidosis
 Metabolism of toxins
 Methanol (wood alcohol)
 ethylene glycol (antifreeze solution)
 Salicylate overdose
 Decreased renal excretion of acids
 Uremia (as seen in renal failure)
 renal tubular acidosis (type 1) distal
 Loss of Bicarbonate
 Renal tubular acidosis type II (proximal)
 GI loss (e.g. in severe diarrhea as well as prolonged vomitting)
 Disease conditions from abnormal metabolism
e.g. Diabetes Mellitus
 Strenuous exercise resulting into accumulation of Lactic Acid
 Metabolic Acidosis
• Treatment
– Treat the underlying condition.
For e.g. control of diabetes with Insulin,
adequate hydration with IV Fluids in mild cases
of acidosis, and dialysis for extreme cases of
renal insufficiency.

19
 Metabolic Alkalosis
 Alkalemia due to loss of acid [H+] or gain of base
[HCO -], resulting in the
3 Plasma HCO - level3

 The loss of H+ causes H CO to dissociate into

2 3

HCO - and H+
3

 Si n ce t h e pri m a ry di s t u rba n ce i s of n on
respiratory origin, PCO remains normal even
2

though H+ falls and HCO - rises.

3

20
 Metabolic Alkalosis
• Treatment

– IV Fluids are administered while treating the

underlying cause

– In severe cases, diluted acids in form of IV

ammonium chloride can be administered.

21
 RESPIRATORY ACIDOSIS
• The rate and depth of breathing control the
amount of CO2 in the blood
• Normally when CO2 builds up, the pH of the
blood falls and the blood becomes acidic
• High levels of CO2 in the blood stimulates
medulla oblongata that regulate breathing,
which in turn stimulate faster and deeper
breathing

22
 Respiratory Acidosis: Renal
compensation
• The renal compensation results in
the retention of HCO and excretion
-
3

of H+

• Plasma [H ] thus decreased towards

+

normal while [HCO ] increased

-
3

further
• These changes occurs over 4 to 5
days
• After which a steady state is
achieved resulting in normalised H
+

excretion and retention of HCO

-
3
 Respiratory alkalosis
 Caused by hyperventilation (i.e. increased elimination of
CO2 from the lungs thereby reducing the PCO2.

 Hyperventilation may be due to anxiety, fever, salicylate

poisoning, hypoxemia at high altitudes, assisted respiration
 The reduced PCO2 results in reduction of both H+ and HCO3-
 If the condition persist, the kidneys will compensate by
increasing the excretion of HCO3- and retaining the H+
 Plasma H+ returns to normal and HCO3- decreases further
 In 3 to 4 days a new steady state is achieved
 RESPIRATORY
Decreased CO in the lungsALKALOSIS
2 will eventually slow
the rate of breathing and permits a normal
amount of CO to be retained in the lung
2
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