This document discusses acid-base balance and homeostasis. It notes that acid-base balance refers to keeping the concentration of hydrogen ions constant in body fluids like blood. The normal pH of arterial plasma is 7.4, and homeostasis involves regulation of pH in extracellular fluids by various mechanisms including buffers, the respiratory system, and kidneys. Disruptions to acid-base balance can have serious physiological consequences.

1. MEDICAL PHYSIOLOGY
POST GRADUATE
Acid – Base Balance

2. - Acid-base balance means keeping H+ ions conc. in body
fluids constant (i.e. ECF; Blood).
- The normal H+ conc. in arterial plasma is 0.00004 mEq/litre.
- Because its’ conc. is VERY low, H+ concentration have been
expressed on logarithm scale, using pH units.
pH = - log [H+]
 Acid - base homeostasis is the homeostatic regulation of the pH
of ECF (i.e. blood).
 The proper balance between acids and bases in the ECF is crucial
for normal body physiology and cellular metabolism.

3. Acid-Base Homeostasis is
CRITICAL
for
• Normal/Optimal Enzyme activities
• Normal metabolism
• Normal Health

4.  Normal blood pH is 7.4, but it may fluctuate from 7.35
to 7.45.
 Values outside the range of (6.8 – 8.0) are typically
incompatible with life due to changes in enzymatic
function & protein denaturation.
Acidemia 7← acidosis ← 7.35 -7.4 → alkalosis → 8 alkalemia
↓ ↓
Coma & death Tetany & convulsions
&death

5. 5

6. Buffers (very rapid control):
Act within a fraction of a second. They are the first line of defense
against changes in the blood pH, but their power is limited.
The respiratory system (relatively rapid control):
Take 1-15 minutes to readjust the pH. It constitutes the second line of
defense against changes in the blood pH.
The kidney( very slow control):
It takes several hours to several days. It constitutes the third line of
defense against changes in the blood pH. They are the most powerful
and most efficient buffering mechanism.
Regulatory mechanisms of acid-base balance

7. Sources &Types
Acids &Alkalies
Added During
Metabolic Life Processes

8. • Acidic Substances in the body:
–Carbonic acid(H2CO3)
–Phosphoric acid( H3PO4)
–Sulphuric acid (H2SO4)
–Organic Acids:
e.g. Lactate, Acetoactate, Pyruvate
• Alkaline Substances in the body:
–Citrate
–Bicarbonates.

9. Acids & Bases can be
Strong or Weak
• A strong acid or base is one that dissociates
completely in a solution
- HCl, NaOH, and H2SO4
• A weak acid or base is one that dissociates
partially in a solution
-H2CO3 , Lactate.

10. The general equation for a buffer (Henderson-Hasselbalch Equation):
HA ↔ H+ + A- (acid reactions are reversible)
And at equilibrium: H+ . A- = K (constant)
HA
So, K. HA = H+ . A- then H+ = K.HA
A-
-log H+ = -log pK - log HA
A-
Rather than work with –logarithm, we can change the sign and invert
the numerator and demoninator in the last term.
pH = pK+ log A-
HA
Strength of any buffer system is determined by 2 factors:
Concentrations of its components.
Closer between pK of the buffer and pH of body fluid where it operates.
Buffers

11. I. Chemical mechanism (i.e. Buffers)
The First line of regulation (most rapid within seconds But weak).
1. Carbonic acid / bicarbonate system:
o It is the most important.
o Its components are Physiologically regulated.
o Kidneys and lungs are the principal organs involved.
2. Reduced / oxidized haemoglobin system (HHb/KHbO2):
o They buffer MOST of the tidal CO2. (~ 85 %)
3. Proteinic acid / proteinate system:
o It buffers part of tidal CO2 (about 5 %).
4. The phosphate system (i.e. NaH2PO4/Na2HPO4):
o It buffers part of tidal CO2 (about 5 %).
5. Tissue buffers: e.g. tissue proteins, phosphates and bicarbonates. .etc.
o They are weaker than blood buffers.
o But due to the large volume of tissues, they are of importance.

12. Site: Extracellular fluids
Components: H2CO3 and HCO3.
HCO3 is present mostly as Na HCO3 and is called the alkali reserve
(normally 24-28 mEq/litre).
CO2 + H2O↔ H2CO3↔ H+ + HCO-
3
pK: 6.1
Points of strength: Its two components can be physiologically regulated.
*HCO3 is regulated by the kidney.
*CO2 is regulated by the respiratory system.
Points of weakness: pK is far from pH of body fluids, and the
concentrations of its two components are not great.
When strong acid such HCl is added to bicarbonate buffer:
HCl+ NaHCO3 → NaCl + H2CO3(very weak acid) → CO2 + H2O
When strong base such NaOH is added to bicarbonate buffer:
NaOH + H2CO3 → Na HCO3 + H2O
The bicarbonate Buffer:

13. Site: Intracellular fluids and the kidney (more concentrated and pH close
to pK)
Components: H2PO-
4 and H PO-
4
pK: 6.8
Points of strength: pK close to pH of body fluids where it operates.
Points of weakness: Its concentration is 1/12 of the bicarbonate system,
so its buffering function is less (as under normal conditions, much of the
filtered phosphate is reabsorbed).
When strong acid such HCl is added to phosphate buffer:
HCl + Na2HPO4→ Na H2PO4 + NaCl
When strong base such NaOH is added to phosphate buffer:
NaOH + Na H2PO4 → Na2HPO4 + H2O
The Phosphate Buffer

14. The most important in the body.
Site: Intracellular and extracellular fluids.
Components:
Plasma proteins: proteinic acid and Na proteinate.
Haemoglobin: It is the most important buffer in the blood, its buffering
power is 6 times that of plasma proteins:
H.Hb and KHb and oxyHb and K oxyHb
pK: around 7.4
Points of strength: pK close to pH of most body fluids where it operates
and very high concentrations of its components.
The Protein Buffer

15. • The second line of defense against pH changes.
• Short term regulatory process (within minutes).
• Powerful, but ONLY works on volatile acids; e.g.
carbonic acid (CO2+H2O).
• Doesn’t affect fixed acids like lactic acid.
• Blood pH is adjusted through respiratory mechanism by
changing rate and depth of breathing.
i.e. Nervous mechanism via Respiratory center
II. Respiratory system

16. • The respiratory center affects the bicarbonate buffer system.
• ↑H+ → stimulates respiratory center → hyperventilation →
↓CO2 concentration in the blood → ↓H+ conc. and vice versa.
• It takes several minutes to act .
• It can never bring the pH all the way back to normal, because as
H+ starts to return to normal, the effect on the respiratory center
decreases.
Role of Respiratory system

17. • The third line mechanism.
• long term regulatory process.
• Slow but the most effective regulator of blood pH.
• Complete as it brings the pH back to normal.
• The acid and alkaline phosphates formed during phosphate
buffering mechanism are filtered from blood and excreted out
through urine.
o Excreting acidic urine in cases of acidosis.
o Excreting basic urine in cases of alkalosis.
• Thus the phosphate buffer system is directly connected to renal
mechanism.
• Conserve & produce Bicarbonate ions (i.e. restore Alkali reserve).
If kidneys fail → pH balance fails
III. The role of the kidney

18. • In cases of acidosis:
1. Increased H+ secretion.
2. Increased reabsorption of filtered bicarbonate.
3. Formation of titratable acids.
• In cases of alkalosis:
1. Increased filtration of NaHCO3.
2. Decreased reabsorption of NaHCO3.
3. Decreased secretion of H+.
Mechanism(s) of Renal System in
Acid Base Balance

19. Reabsorptionof filtered buffers:
Bicarbonatereabsorption

20. Formationof titratable acids:
Titrationof H+ occurs with phosphates buffer

23. In PCTS:
• Maximal acidifying power up to 6.9
• H+ secretion: in exchange with Na+ ONLY.
• By 2ry active countertransport.
• NOT under hormonal control.
• Carbonic anhydrase enzyme is essential.
In DCTs and CDs:
• Maximum acidifying power is 4.5
• H+ secretion: in exchange with K+ or active H+ pump.
• under control of aldosterone hormone (i.e. it stimulates
Hydrogen ATPase) .
• Carbonic anhydrase enzyme is essential.

24. Significance of ammonia:
H+ secretion in DCTs and CDs occurs only as long as the pH of
the fluid in these segments is more than 4.5. If the secreted
H+ is not buffered, pH of the tubular fluid may drop below 4.5,
in which further H+ secretion would stop and acidemia may
result. Ammonia is responsible for continuation of this
secretion of H+
Ammonia adaptation: Ability of ammonia to be secreted as
long as H+ is secreted.
Control of ammonia secretion: Once ammonia is secreted it
transformed into NH4Cl →↓level of free ammonia in tubular
fluid→ maintain ammonia gradient →maintain secretion.
Role of Ammonia

25. Clinical significance:
In cases of diabetic ketoacidosis:
NH4 excretion is increased because acidosis induces the
enzymes involved in glutamine metabolism, thereby
increasing NH3 synthesis.
In chronic renal failure:
There is metabolic acidosis. In this disease, there is
progressive loss of nephrons→ ↓GFR→↓filtration load of
phosphate, also ↓ synthesis of ammonia in the diseased
nephrons. So persons with chronic renal failure are placed on
a low-protein diet to reduce daily fixed H+ production.

26. The partial pressure of carbon dioxide [pCO2] is controlled by the lungs. For this
reason it is called ‘the respiratory component of the acid–base balance’. On the other
hand, plasma bicarbonate concentration [HCO3
-] is controlled by the kidneys and
erythrocytes and, consequently, it is called ‘the metabolic component of the acid–base
balance
RESPIRATORY AND METABOLIC COMPONENTS OF ACID BASE
BALANCE
The bicarbonate buffer. Blood pH is
proportional= ‫تتناسب‬
‫مع‬ to the ratio of
plasma bicarbonate to the partial pressure
of carbon dioxide (pCO2). The
components of the bicarbonate buffer are
thus the carbon dioxide and the
bicarbonate. The pCO2 is the respiratory
component of acid– base balance, and
bicarbonate is the metabolic component.
26

27. Causes of Respiratory acidosis
(i.e. ↑ free CO2)
1. Breathing air containing high concentration of CO2.
2. Obstructive airway diseases.
3. Pulmonary diseases affecting gas exchange.
4. Depression of respiratory centre e.g. morphine poisoning.
• Acute conditions:
1. Adult Respiratory Distress Syndrome
2. Pulmonary edema
3. Pneumothorax
Chronic conditions:
1. Depression of respiratory center in brain that controls breathing rate
– drugs or head trauma
2. Paralysis of respiratory or chest muscles
3. Emphysema
4. Asthma
5. Pneumonia
6. Pulmonary edema
7. Obstruction of respiratory tract
8. Congestive Cardiac Failure

28. Respiratory Alkalosis
• Primary cause is hyperventilation
• Decreased H2CO3
• Conditions that stimulate respiratory center:
1. Oxygen deficiency at high altitudes
2. Pulmonary disease and Congestive heart failure
– caused by hypoxia
3. Respiratory center lesions
4. Acute anxiety
5. Fever, anemia

29. Metabolic acidosis (i.e. ↓ HCO3
-):
Causes:
1. High protein metabolism due to the production of sulphuric and
phosphoric acids.
2. Severe muscular exercise due to excessive formation of lactic acid.
3. ↑ Fat oxidation as in starvation and diabetes mellitus → ↑ acid
ketone bodies.
4. Ingestion of acidifying salts as ammonium chloride.
5. Renal failure due to lack of ammonia formation and failure of H+
secretion.
6. Hypofunction of adrenal cortex (Addison's disease) due to excessive
loss of Na+ and retention of H+
7. Laxative abuse. (Because intestinal secretions ordinarily contain
relatively high HCO3 concentration, diarrhea normally results in a
metabolic acidosis).

30. Metabolic alkalosis (↑ NaHCO3)
Causes:
1. Ingestion of excess bicarbonate e.g. during treatment of
peptic ulcer.
2. During gastric secretion (i.e. each H+ ion secreted is
associated with bicarbonate ion reabsorbed → called alkaline
tide).
3. Hyper function of adrenal cortex (Cushing syndrome); Na+
is reabsorbed in exchange with H+ which is secreted in urine.
4. Persistent vomiting due to HC1 loss.