Acid and Base Balance and its

Disorders
Presented byDr. Hasan Hafizur Rahman
Phase- A resident student
Dept.of Nephrology.DMC.

Definitions
Acid (HA) is defined as a compound that can release a
proton (H+)
Acidosis (acidaemia) is defined as a disorder with
accumulation of acids in the extended ECV. The pH in the
arterial blood is < 7.35
Base (B-)is defined as a compound can bind H+

Conti Alkalosis (alkalaemia) is defined as a condition with

accumulation of bases in the extended ECV. The
pH of the arterial blood is 7.45
Buffer is a mixture of compounds which have the
ability to absorb small amounts of H+ or OH- with
very little change of pH.

Conti Buffer
Combination of a weak acid and /or a weak base
and its salt
What does it do?
Resists changes in pH
Effectiveness depends on
pK of buffering system
pH of environment in which it is placed

 pK:
Negative log of the ionization constant of an acid
Strong acids would have a pK <3
Strong base would have a pK >9
pH
Negative log of the hydrogen ion concentration
pH= pK + log([base]/[acid])
Represents the hydrogen concentration

pH Review

pH = - log [H+]
H+ is really a proton
Range is from 0 - 14
If [H+] is high, the solution is acidic; pH < 7
If [H+] is low, the solution is basic or alkaline; pH > 7

 Acids are H+ donors.

Bases are H+ acceptors, or give up OH- in solution.
Acids and bases can be:
Strong dissociate completely in solution
HCl, NaOH
Weak dissociate only partially in solution
Lactic acid, carbonic acid

The Body and pH

Homeostasis of pH is tightly controlled

Extracellular fluid = 7.4
Blood = 7.35 7.45
< 6.8 or > 8.0 death occurs
Acidosis (acidemia) below 7.35
Alkalosis (alkalemia) above 7.45
Production of 1 mmol of fixed acid/kg body weight per
day (60 kg=60 mmol/day)
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ContiNormally, the [H+] of arterial blood of humans is

maintained by the lungs, kidneys and liver within
the range of 40 5 nM, corresponding to a
pH of 7.35 - 7.45.
pH = - log (40 x 10-9 mol/L ) = 7.4
A pH of 6.8 - 6.9 is not sustainable for long, and the
patient is dying in a state of coma

Production of acids
CO2 is a potential acid as H2CO3, and because the lungs
eliminate it, it is called a volatile acid. Production of CO2
is up to 24 mol daily.
Non-volatile acids:
a) Organic acids are continually produced as a byproduct of metabolism:
- lactic acid.ketoacids, Fatty acids
Under normal conditions, these acids are completely
metabolized to CO2 and H2O. They have no effect on
proton balance.

b) inorganic acids: excretion by kidneys

H2SO4 HSO4- + H+
H3PO4 HPO42- + H+
Note: H+ are also released from acids in the diet
e. g. citric acid, ascorbic acid

The body maintains ECF physiologic

pH by buffers
Bicarbonate buffer HCO3- / CO2
(53%)
Hemoglobin (Hb) in RBC
(35%)
Plasma proteins (mainly albumin)
(7%)
Phosphate buffer HPO42- / H2PO4(3%)
NH3/NH4+ and HPO42-/H2PO4- are the most important
urinary buffer systems.
About 30 mmol of NH4+ is excreted in the daily urine,
but the excretion is controlled during acid-base
disorders.

HCO3-/CO2-buffer system
HCO3- and CO2 are present in ratio of about 20 : 1.
CO2 is dissolved in the plasma and it is constantly
exchanging with CO2 in the gas phase of the alveoli
of the lungs.

ContiCO2 (pCO2) elimination is controlled by lungs

It takes 1 3 min to respond to changes in pH and effect
changes in the pH.
ventilation pCO2 alkalinization
ventilation pCO2 acidification
HCO3- elimination is controlled by kidneys.
It takes several hours to days for urinary system to
compensate for changes in pH.
Liver: Urea cycle: CO2 + 2 NH4 urea + 2 H+ + H2O

Laboratory analysis of ABB state

Determination of pH, HCO3-, pCO2, pO2 and BE
Determination of concentration ofCations (Na+, K+, Ca2+, Mg2+),
Anions (Cl-, lactate) and
Metabolites (urea, creatinine, ketone bodies)
Normal values of:
HCO3- = 22 26 mmol/L
BE = from 2.5 to + 2.5 mmol/L

ContiBE (base excess) is defined as the amount of acid

that would be added to blood to titrate it to pH 7.4 at
pCO2 = 40 mmHg.
Positive value = base excess
Negative value = base deficit (BD)

Anion gap (AG)

AG represents the plasma anions which are not routinely
measured (albumin, phosphates, sulphates, & organic anions).
AG is calculated as follows:
AG = (Na+ + K+) (HCO3- + Cl-)
The sum of the concentrations of Na + and K+ is greater than
the sum of concentrations of HCO 3- and Cl-. Difference is called
as a anion gap.
Normal values of AG: 16 20 mmol/L
AG is calculated in case of metabolic acidosis

Respiratory acidosis (RAc)

RAc is caused by hypoventilation (or breathing of CO2
containing air). Hypoventilation is associated with
accumulated CO2 reduces the arterial pH.
Causes: --airway obstruction,
- neuromuscular disorders,
- disorders of CNS,
-opiate poisoning
Compensation: reabsorption of HCO3- is performed by
kidneys (proximal tubule)

Respiratory alkalosis (RAl)

The hyperventilation is disproportionately high
elemination compared to the CO2 production, whereby
the pCO2 falls and the pH increases
Causes:
- CNS injury, salicylate poisoning,
- fever, anxiety. hysterical hyperventilation
Compensation: renal excretion of HCO3- plasma
pH decreases toward normal pH

Metabolic acidosis (MAc)

MAc is caused by accumulation of acids in ECF.
(negative BE)
Causes:
-Hypoxia anaerobic glycolysis lactate acidosis
-DM, starvation ketoacidosis
-Ingestion of methanol or ethylene glycol
-Diarrhoea
Compensation:
-1st step: buffering of excess of H+ by HCO3-2nd step: respiratory compensation by hyperventilation
-3rd step: renal correction excretion of H+ in urine

Metabolic alkalosis (MAl)

MAl is caused by a primary accumulation of bases in ECF.
(Positive BE) .
Causes:
-Ingestion of alkaline drugs (e. g. NaHCO3)
-Prolonged vomiting loss of H+
Compensation:
-1st step: buffering of excess of HCO3-2nd step: respiratory compensation by hypoventilation
pCO2 in alveoli and arterial blood
-3rd step: renal correction: excretion of HCO 3- in urine

Defenses against pH shift

Hemoglobin Buffer System

Roles
Binds CO2
Binds and transports hydrogen and oxygen
Participates in the chloride shift
Maintains blood pH as hemoglobin changes
from oxyhemoglobin to deoxyhemoglobin

Oxygen Dissociation Curve

Curve B: Normal curve

Curve A: Increased affinity for

Hb, so oxygen keep close

Curve C: Decreased affinity for

Hb, so oxygen released to
tissues

Henderson-Hasselbalch Equation
Relationship between pH and the bicarbonatecarbonic acid buffer system in plasma
Allows us to calculate pH

Henderson-Hasselbalch Equation
General Equation
pH = pK + log AHA
Bicarbonate/Carbonic Acid system
o

pH= pK + log HCO3

H2CO3 ( PCO2 x 0.0301)

Physiologic effects of Acidosis

Clinical effects of severe acidosis: pH <7.2

Cardiovascular system effectsDecreased myocardial contractility

Decreased cardiac output
Cardiac failure
Hypotension
Decreased hepatic and renal blood flow
Centralization of effective blood volume
Tissue hypoxia
Pulmonary edema

Conti Respiratory effects-hyperventilation

-shift of oxyHb dissociation curve to the right
- 2,3 DPG level in the RBC which oppose
the above effect. This effect occurs after 6
hrs of acidemia
CNS effect- cerebral vasodilation ICP
- very high Co2 level will cause central
depression

Conti Severe acidosis causes

Disorientation
coma
death
Other effects
-chronic M. acidosis bone resorption
- hyperkalaemia due K+ shift out of cell
-ECF phosphate concentration

Alkalosis

Differential Diagnosis of Metabolic

Acidosis
Normal anion gap
Increased anion gap
(hyperchloemic)
(organic)
- acid production
GI loss of HCO3 Diarrhea
Lactic acidosis
Renal tub. Acidosis
- Diab. Ketoacidosis
Parenteral alimentation
Toxic alcohol,salicy.
Carbonic anhydr. nh.
- Acute renal failure
K-sparing diuretics
- Chronic renal failure

Increased anion gap

Metabolic acidosis

Ketoacidosis (diabetic)
Uremia (renal failure)
Salicylate intoxication
Starvation
Methanol intoxication
Alcohol ketoacidosis
Unmeasured osmoles (intoxication)
Lactic acidosis

Acid-Base Imbalances
The body response to acid-base imbalance is called
compensation
May be complete if brought back within normal
limits
Partial compensation if range is still outside
norms.

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Compensation
If underlying problem is metabolic, hyperventilation
or hypoventilation can help : respiratory
compensation.
If problem is respiratory, renal mechanisms can
bring about metabolic compensation.

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Diagnosis of Acid-Base
Imbalances
1. To be noted whether the pH is low (acidosis) or high

(alkalosis)
2. To decide which value, pCO2 or HCO3- , is outside the

normal range and could be the cause of the problem. If

the cause is a change in pCO2, the problem is respiratory.
If the cause is HCO3- the problem is metabolic.
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3.To look at the value that doesnt correspond to the

observed pH change.

If it is inside the normal range, there is no

compensation occurring.

If it is outside the normal range, the body is

partially compensating for the problem.

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THANKS A LOT.

Compensatory Response
One half of acid load is buffered by nonbicarbonate buffers= Bone,
protein, red cells..
PCO2 (Kussmaul)
compensatory response after 15-30 minutes,
5 days up to maximal
Kidney:
Metabolic acidosis
processing of glutamine into NH4+ (ammonia to ammonium for
better H-excretion)
and
Bicarbonate generation (and reclaiming)

Respiratory Acidosis
Acute increase in pCO2

Buffered primarily by intracellular buffers

Chronic state:

Kidneys compensation:
Increase net acid excretion,
(48 hours for fully development)

Underlying cause:
Central nervous system disease,
lung (COPD)and heart disease,
sedatives and opiates depressing the respiratory
center
Hypercapnic encephalopathy can develop

Metabolic Alkalosis
Plasma bicarbonate [HCO3-] = pH
1) H+ GI loss or shift into cells
2) Excess HCO3Administration of bicarbonate, or precursors:
lactate, acetate, citrate or
Failure to excrete: mineralocorticoid effect
3) Loss of fluid wih
Diuretic therapy
[Cl-, [K+] and [H+] loss from plasmaextracellular volume contraction

Volume Depletion and Metabolic Alkalosis

Absolute volume depletion:
Loss of salt by bleeding or vomitting or
Effective volume depletion:
Heart failure, cirrhosis, nephrotic syndrome
whenever
GFR
Tubular HCO3- reabsorption

Because proximal tubule reabsorption is enhanced for

Na and water

Compensatory Respiratory Response

Alveolar hypoventilation(hypercapnia)
(limited pCO2 rise to 50-60 mm Hg)
Kidneys:
Excretion of HCO3- proportional to GFR
(excessive)

Respiratory Alkalosis
pCO2 , pH due to:
Hypoxia (compensatory hyperventilation)
Acute: pulmonary edema or emboli, pneumonia,
Chronic: severe anemia, high altitude, hypotension
Respiratory center stimulation
Pregnancy, Anxiety, Fever, heat stroke, sepsis, salisylate
intox., cerebral disease, hepatic cirrhosis,
Increased mechanical ventilation

Respiratory Alkalosis
Most common acid-base disorder
Physiologic in pregnancy and high altitude
Bad prognosis in critically ill patients
(the higher hypocapnia, the higher mortality)
Hyperventilation,
Perioral and extremity paresthesias,
Light-headedness,
Muscle cramps,
Hyperreflexia, seizures, ionized Ca tetany

Acid-Base Balance
Function
Maintains pH homeostasis
Maintenance of H+ concentration
Potential Problems of Acid-Base balance
Increased H+ concentration yields decreased pH
Decreased H+ concentration yields increased pH

Regulation of pH

Direct relation of the production and retention of acids and bases

Systems
Respiratory Center and Lungs
Kidneys
Buffers
Found in all body fluids
Weak acids good buffers since they can tilt a reaction in the
other direction
Strong acids are poor buffers because they make the system
more acid

Bicarbonate/carbonic acid buffer system

How is CO2 transported?
5-8% transported in dissolved form
A small amount of the CO2 combines directly with the
hemoglobin to form carbaminohemoglobin
92-95% of CO2 will enter the RBC, and under the
following reaction
CO2 + H20

H+ + HCO3-

Once bicarbonate formed, exchanged for chloride

 Bicarbonate/carbonic acid buffer

system
Function almost instantaneously
Cells that are utilizing O2, produce CO2, which builds
up. Thus, more CO2 is found in the tissue cells than in
nearby blood cells. This results in a pressure (pCO2).
Diffusion occurs, the CO2 leaves the tissue through
the interstitial fluid into the capillary blood

Small changes in pH can produce

major disturbances
Most enzymes function only with narrow
pH ranges
Acid-base balance can also affect
electrolytes (Na+, K+, Cl-)
Can also affect hormones

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The body produces more acids

than bases
Acids take in with foods
Acids produced by metabolism of lipids
and proteins
Cellular metabolism produces CO2.
CO2 + H20 H2CO3 H+ + HCO3-

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Control of Acids
1. Buffer systems
Take up H+ or release H+ as conditions
change
Buffer pairs weak acid and a base
Exchange a strong acid or base for a
weak one
Results in a much smaller pH change
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Bicarbonate buffer
Sodium Bicarbonate (NaHCO3) and
carbonic acid (H2CO3)
Maintain a 20:1 ratio : HCO3- : H2CO3
HCl + NaHCO3 H2CO3 + NaCl
NaOH + H2CO3 NaHCO3 + H2O
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Phosphate buffer
Major intracellular buffer
H+ + HPO42- H2PO4 OH- + H2PO4- H2O + H2PO42-

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Protein Buffers

Includes hemoglobin, work in blood and ISF

Carboxyl group gives up H+
Amino Group accepts H+
Side chains that can buffer H+ are present on
27 amino acids.

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2. Respiratory mechanisms
Exhalation of carbon dioxide
Powerful, but only works with volatile
acids
Doesnt affect fixed acids like lactic acid
CO2 + H20 H2CO3 H+ + HCO3 Body pH can be adjusted by changing rate
and depth of breathing
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3. Kidney excretion

Can eliminate large amounts of acid

Can also excrete base
Can conserve and produce bicarb ions
Most effective regulator of pH
If kidneys fail, pH balance fails

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Rates of correction
Buffers function almost instantaneously
Respiratory mechanisms take several
minutes to hours
Renal mechanisms may take several
hours to days

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Acidosis
Principal effect of acidosis is depression of the
CNS through in synaptic transmission.
Generalized weakness
Deranged CNS function the greatest threat
Severe acidosis causes
Disorientation
coma
death
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Alkalosis
Alkalosis causes over excitability of the central
and peripheral nervous systems.
Numbness
Lightheadedness
It can cause :
Nervousness
muscle spasms or tetany
Convulsions
Loss of consciousness
Death
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Respiratory Acidosis
Carbonic acid excess caused by blood
levels of CO2 above 45 mm Hg.
Hypercapnia high levels of CO2 in blood
Chronic conditions:
Depression of respiratory center in brain that
controls breathing rate drugs or head
trauma
Paralysis of respiratory or chest muscles
Emphysema
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Respiratory Acidosis
Acute conditons:
Adult Respiratory Distress Syndrome
Pulmonary edema
Pneumothorax

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Compensation for Respiratory

Acidosis
Kidneys eliminate hydrogen ion and retain
bicarbonate ion

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Signs and Symptoms of

Respiratory Acidosis

Breathlessness
Restlessness
Lethargy and disorientation
Tremors, convulsions, coma
Respiratory rate rapid, then gradually
depressed
Skin warm and flushed due to vasodilation
caused by excess CO2
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Treatment of Respiratory Acidosis

Restore ventilation
IV lactate solution
Treat underlying dysfunction or disease

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Respiratory Alkalosis

Carbonic acid deficit

pCO2 less than 35 mm Hg (hypocapnea)
Most common acid-base imbalance
Primary cause is hyperventilation

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Respiratory Alkalosis
Conditions that stimulate respiratory
center:
Oxygen deficiency at high altitudes
Pulmonary disease and Congestive heart
failure caused by hypoxia
Acute anxiety
Fever, anemia
Early salicylate intoxication
Cirrhosis
Gram-negative sepsis

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Compensation of Respiratory
Alkalosis
Kidneys conserve hydrogen ion
Excrete bicarbonate ion

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Treatment of Respiratory Alkalosis

Treat underlying cause
Breathe into a paper bag
IV Chloride containing solution Cl- ions
replace lost bicarbonate ions

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Metabolic Acidosis
Bicarbonate deficit - blood concentrations of
bicarb drop below 22mEq/L
Causes:
Loss of bicarbonate through diarrhea or renal
dysfunction
Accumulation of acids (lactic acid or ketones)
Failure of kidneys to excrete H+

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Symptoms of Metabolic Acidosis

Headache, lethargy
Nausea, vomiting, diarrhea
Coma
Death

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Compensation for Metabolic

Acidosis
Increased ventilation
Renal excretion of hydrogen ions if
possible
K+ exchanges with excess H+ in ECF
( H+ into cells, K+ out of cells)

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Treatment of Metabolic Acidosis

IV lactate solution

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Metabolic Alkalosis
Bicarbonate excess - concentration in
blood is greater than 26 mEq/L
Causes:
Excess vomiting = loss of stomach acid
Excessive use of alkaline drugs
Certain diuretics
Endocrine disorders
Heavy ingestion of antacids
Severe dehydration
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Compensation for Metabolic

Alkalosis
Alkalosis most commonly occurs with
renal dysfunction, so cant count on
kidneys
Respiratory compensation difficult
hypoventilation limited by hypoxia

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Symptoms of Metabolic Alkalosis

Respiration slow and shallow

Hyperactive reflexes ; tetany
Often related to depletion of electrolytes
Atrial tachycardia
Dysrhythmias

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Treatment of Metabolic Alkalosis

Electrolytes to replace those lost
IV chloride containing solution
Treat underlying disorder

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Example
A patient is in intensive care because he
suffered a severe myocardial infarction 3
days ago. The lab reports the following
values from an arterial blood sample:
pH 7.3
HCO3- = 20 mEq / L ( 22 - 26)
pCO2 = 32 mm Hg (35 - 45)

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Diagnosis
Metabolic acidosis
With compensation

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