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ACID-BASE BALANCE

AND DISORDERS
PRESENTED BY;
ONI MARVELLOUS OLAMIDE

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OUTLINE
 Introduction
 Acid-Base Homeostasis
 Acid-Base Control Systems
 Acid-Base Disorders
 Acidosis
 Alkalosis
 Conclusion
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INTRODUCTION
The tendency of the body to stabilize the composition of the
extracellular fluid is called homeostasis.
• Acid-base homeostasis depends on the integrated action of the
liver, the lungs and the kidney and, to a lesser extent, the
gastrointestinal tract, as well as on the efficient working of
the physiological buffers in both the extracellular and
intracellular compartments.

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ACID-BASE HOMEOSTASIS
 This process of regulating the acid-base levels of
extracellular fluid is why the extracellular H+ concentration is
maintained at about 40 nmol/L (pH 7.4) despite our cells
releasing between 50 and 100 mmol of H+ into the ECF daily.
 The 7.4 pH of blood is the state of equilibrium between
proton donors (acids) and proton acceptors (bases) and is
maintained at a certain range under normal conditions in
arterial blood.
 Acids can dissociate to produce H+ (protons), which can be
accepted by a base. A base (alkali) dissociates to produce
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hydroxyl ions (OH-).
ACID-BASE HOMEOSTASIS
Acidosis is commoner than alkalosis because
metabolism tends to produce H+ rather than OH-.
A strong acid is almost completely dissociated in
aqueous solution, and so produces many H+ e.g.
HCl → H+ + CL-
Weak acids dissociate less, although very small
changes in H+ may have important consequences e.g.
H2CO3 → H+ + HCO3-
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THE BODY AND PH

 The pH is a measure of H+ activity. It is log 10 of the


reciprocal of H+ in mol/L.
 The H+ concentration is inversely related to pH.
 The pH of plasma is 7.4 (average hydrogen ion
concentration of 40 nanomoles/liter) is tightly controlled.
 The variation of plasma pH is very small. The pH of
plasma is maintained within a narrow range of 7.35 to
7.45.
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ACID–BASE CONTROL SYSTEMS
 Acid–base regulation is under the control of 3 systems.
 The first system which is also the first line of defence in
this regulation process is the blood buffer system. This
gives immediate response to imbalance in acid-base
levels.
 The second system and line of defence is the respiratory
system. This offers temporary response.
 The third line of defence is the renal system. This
provides a permanent response to changes in acid-base 9
balance.
1. THE BUFFER SYSTEM
 Buffering is a process by which a strong acid (or base) is replaced
by a weaker one, with a consequent reduction in the number of free
H+, and therefore the change in pH, is less than it would be in the
absence of the buffer.
 For example: H+ Cl- + NaHCO3 ↔ H2CO3+ NaCl
• (strong acid) (buffer) (weak acid) (neutral salt)
 The Henderson–Hasselbalch equation expresses the relation
between pH and a buffer pair – that is, a weak acid and its conjugate
base.

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THE BUFFER SYSTEM
This equation is valid for any buffer pair, the pH being
dependent on the ratio of the concentration of base to acid.
The pKa is the negative logarithm of Ka which is
inversely proportional to pH.
•pH = pKa+log[base] /[Acid]

The three most important buffers are:


Bicarbonate buffer
Phosphate buffer
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Ammonia buffer
BICARBONATE BUFFER
• It consists of bicarbonate (HCO3-) and carbonic acid (H2CO3)

• HCl + NaHCO3 ↔ H2CO3 + NaCl


• (strong acid) (buffer) (weak acid) (neutral salt)
•In this equation the base is bicarbonate (HCO3 – ) and the acid is
carbonic acid (H2CO3). It is not possible to measure the latter directly;
however, it is in equilibrium with dissolved CO2 , of which the partial
pressure (PCO2 ) can be estimated.
 The concentration of H2CO3 is derived by multiplying this
measured value by the solubility constant (S) for CO2 .
 Thus: pH = pKa + log [HCO3 – ] / PCO2 x S
• It has a pKa value of 6.1 and is ideal for plasma buffers 12
BICARBONATE BUFFER
Considering that pKa is most effective when nearest to the
body’s pH value, this 6.1 pH may seem to be
disadvantageous, but the bicarbonate system is the most
important buffer in the body because:
● It accounts for more than 60 per cent of the blood
buffering capacity.
● H+ secretion by the kidney depends on it.
● It is necessary for efficient buffering by haemoglobin
(Hb), which provides most of the rest of the blood
buffering capacity. 13
BICARBONATE RECLAMMATION
 Bicarbonate is filtered through the glomeruli at a plasma
concentration of about 25 mmol/L.
 Filtered HCO3 combines with H ion secreted by tubular cells,
to form H2CO3 The H2CO3 dissociates to form CO2 and water.
 In the proximal tubules this reaction is catalysed by CD. In
the distal tubules, where the pH is usually lower, H2CO3
dissociates spontaneously.
 As the luminal PCO2 rises, it diffuses into tubular cells along a
concentration gradient and as its intracellular concentration rises,
CD catalyses its combination with water to form H2CO3
which dissociates into hydrogen ion and bicarbonate.
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 Hydrogen ions are then secreted in the tubular lumen
in exchange for Na and so the HCO3- generation
begins again.

 As the intracellular concentration of HCO3- rises, it


diffuses into the ECF accompanied by Na.

 This cycle continues to reclaim the buffering capacity


that would otherwise have been lost from the body by
glomerular filtration
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2. RESPIRATORY SYSTEM
• Occurs by activation or inhibition of the respiratory
center in respect to CO2.
• Chemoreceptors help sense changes in [CO2] and
mediate appropriate ventilation response.
• CO2 + H20 ↔ H2CO3 ↔ H+ + HCO3-
• Body pH can be adjusted by changing the rate and depth
of breathing.

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THE CONTROL OF CO2 BY THE LUNGS
 The partial pressure of CO2 (pCO2) in plasma is
normally about 5.3 kPa (40 mmHg) and depends on the
balance between the rate of production by metabolism
and the loss through the lungs.
 Inspired oxygen (O2) is carried from the lungs to the
tissues by Hb.
 The tissue cells use the O2 for aerobic metabolism; some
of the carbon in organic compounds is oxidized to CO2.
 CO2 diffuses along a concentration gradient from the
cells into the ECF and is returned by the blood to the
lungs, where it is eliminated in expired air.
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 The rate of respiration, and therefore the rate of CO2
elimination, is controlled by chemoreceptors in the
respiratory centre in the medulla of the brainstem and by
those in the carotid and aortic bodies.

 The receptors respond to changes in the [CO2 ] or [H+]


of plasma or of the cerebrospinal fluid. If the PCO2 rises
much above 5.3 kPa, or if the pH falls, the rate of
respiration increases.

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3. RENAL SYSTEM
• Can eliminate large amounts of acid and base.
• Can conserve and produce bicarbonate ions.
• Most effective regulator of pH
• If kidneys fail, pH balance fails.

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RENAL SYSTEM
The renal regulation system works by;
• Excretion of hydrogen ions and reabsorption of
bicarbonate alongside sodium ion into the ECF
• Excretion of acid anions:
Acid anions, such as sulphate ion and phosphate ion, are
filtered by the glomerulus and, providing the GFR is
normal, excreted in the urine.

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RATES OF CORRECTION
• The buffer system, being the first line of defense in
acid-base regulation. It functions almost
instantaneously.
• Respiratory system as the second line of defense takes
several minutes to hours. This is a temporary response
to change in acid-base balance.
• Renal system is the third line of defense. It may take
several hours to days to kick off. This provides a
permanent response.

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ACID-BASE DISORDERS

There are four simple acid-base disorders;


Metabolic acidosis.
Metabolic alkalosis.
Respiratory acidosis.
Respiratory alkalosis.

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ACID BASE DISORDERS
Acid-base status is generally evaluated by a blood gas analysis
 Presented as pH, pCO2, and HCO3-.

 The pH evaluates the hydrogen ion concentration:

Low pH = acidaemia
High pH = alkalaemia.
 The pCO2 reflects the respiratory component:

High pCO2 = respiratory acidosis,


Low pCO2 = respiratory alkalosis.
 The HCO3- indicates the metabolic component:

High HCO3- = metabolic alkalosis,


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Low HCO3- = metabolic acidosis
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COMPENSATION
• The body’s response to acid-base disorder is called
Compensation.
• May be Complete if brought back within normal limits;
Partial compensation if range is still outside normal.
• 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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ACIDOSIS

Acidosis occurs if there is a fall in the ratio of [HCO3-] to


pCO2 in the ECF. It may be due to:
It may be due to metabolic acidosis (primary abnormality in the
bicarbonate buffer system is reduction in HCO3-) or respiratory
acidosis (primary abnormality in the bicarbonate buffer system is a
rise in pCO2).

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METABOLIC ACIDOSIS
•The primary disorder in metabolic acidosis is a bicarbonate deficit, resulting
in a fall in blood pH.
•pH = pKa + log[HCO3-]/[H2CO3] since H2CO3 is an aqueous solution of
CO2.
The reduction in the HCO3– may be due to;
 its use in buffering H+ more rapidly than it can be generated by normal
homeostatic mechanisms
 loss in the urine or gastrointestinal tract more rapidly than it can be
generated by normal homeostatic mechanisms
 impaired production.
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PLASMA ANION GAP
 One negative charge balances one positive charge and
some substances are multivalent, having more than one
charge per mole
 Sodium and potassium provide more than 90% of the
plasma cation concentration in a healthy subject, the
balance include low concentration of magnesium and
calcium which vary only in small amounts.
 Cl- and HCO3- makes up 80% of the plasma anion
concentration, the remaining 20% (sometimes referred to
as unmeasured anion) is accounted for by protein and
normally low concentration of urate, phosphate,
sulphate, lactate and other organic anions. 31
 The protein concentration remains relatively constant, but the
concentrations of other unmeasured anions can vary
considerably in disease.
 The anion gap, represented as A- in the following equations, is
the difference between the total concentration of measured
cations (Na+ and K+) and measured anions (Cl- and HCO3
 it is normally about 15–20 mEq/L.

 Therefore:

[Na+] + [K+] = [HCO3–] + [Cl–] + [A–]


140 + 4 = 25 + 100 + 19 mEq/L

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HIGH ANION GAP ACIDOSIS
 CAUSES OF HIGH ANION GAP ACIDOSIS
 Diabetic Ketoacidosis

 Renal Ketoacidosis

 Methanol

 Alcohol Ketoacidosis

 Paracetamol

 Lactic Acidosis

 Ethylene glycol

 Salicylates

 A useful mnemonic for this is DR MAPLES


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LACTIC ACIDOSIS
 It is a common form of high anion gap metabolic
acidosis.
 Arterial pH of less than 7.2 with plasma lactate
concentration greater than 5mmol/l
 Normal fasting blood lactate is between 0.4-1mmol/l

 There are 3 types;


o Type A: as a result of tissue hypo-perfusion

o Type B1: due to organ dysfunction including severe

hepatic disturbance
o Type B2: due to drugs and toxins

o Type B3: due to metabolic disorders and inborn errors 34


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SYMPTOMS OF METABOLIC ACI-
DOSIS
In MA, there’s associated hyperkalemia. Here, K+
exchanges with excess H+ in ECF( H+ into cells, K+ out
of cells) in an attempt to maintain electrical neutrality.
This raises the level of K+ in the ECF.
Symptoms of MA are:
• Headache, lethargy
• Nausea, vomiting, diarrhea
• Coma
• Death
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COMPENSATION FOR METABOLIC
ACIDOSIS
• The body will seek to compensate by respiratory
alkalosis through hyperventilation.
• Renal excretion of hydrogen ions if possible

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RESPIRATORY ACIDOSIS
•Respiratory acidosis differ significantly from those in
non-respiratory disturbances. The primary abnormality
is CO2 retention.
•This is usually due to impaired alveolar ventilation
with a consequent rise in PCO2 above 45 mm Hg
(hypercapnia).
Normal range is 35mmHg – 45mmHg.
 As in the metabolic disturbance, the acidosis is
accompanied by a fall in the ratio of [HCO3 – ] to
PCO2. 38
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COMPENSATION FOR RESPIRATORY
ACIDOSIS

• Kidneys eliminate hydrogen ion and retain bicarbonate


ion
• Hyperventilation.

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ALKALOSIS
Alkalosis occurs if there is a rise in the ratio of HCO3- to
pCO2 in the ECF.
In metabolic alkalosis, primary abnormality is a rise in
HCO3-
While in respiratory alkalosis, the abnormality is a fall in
the CO2
As the primary products of metabolism are H+ and CO2,
not OH and HCO3-, alkalosis is less common than acidosis.

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RESPIRATORY ALKALOSIS

 This is due to abnormally rapid or deep respiration


when the CO2 transport capacity of the pulmonary
alveoli is relatively normal.
• pCO2 less than 35 mm Hg (hypocapnea)

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COMPENSATION OF RESPIRA-
TORY ALKALOSIS
• Kidneys conserve hydrogen and excrete bicarbonate ion

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METABOLIC ALKALOSIS

This is a primary rise in plasma bicarbonate [HCO3-] i.e.


a blood concentration greater than 26 mmol/L. This can
be caused by
Bicarbonate administration, such as the ingestion
of large amounts of HCO3- to treat indigestion or
during intravenous HCO3- infusion.
•Vomiting , which causes loss of hydrogen and chloride
ions and volume depletion, is the most common cause of
a metabolic alkalosis.

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• Excessive use of alkaline drugs
• Certain diuretics, thiazide or loop diuretics
• Endocrine disorders e.g. Conn's syndrome
• Severe dehydration

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COMPENSATION FOR METABOLIC
ALKALOSIS
• Respiratory acidosis via hypoventilation although may
be limited by hypoxia.
Antiemetics may help stop vomiting, and proton pump
inhibitors may reduce gastric acid secretion.
If the patient is on a thiazide or loop diuretic, this may
need to be reduced or stopped.

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CONCLUSION
 The importance of acid-base balance is of great
importance to the well-being of the body and for the
normal functioning of all systems of the body.

 Any sign of derangement in the levels of acid or base


should be corrected immediately to avoid loss of
function or damage to any organ or system.

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REFERENCES
●Clinical Biochemistry & Metabolic Medicine written
by Professor Martin Andrew Crook BSc. MB. BS. MA.
PhD. FRCPath. FRCPI. FRCP.
●A PRIMER OF CHEMICAL PATHOLOGY BY N.
C EVELYN & N. WALMSLEY. 3RD ED.

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THANKS FOR
LISTENING!

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