1. Life is a struggle,
not against sin,
not against
Money Power . .
But against
hydrogen ions.
Dr. Mamta
Khandelwal
1
2. Why acid base homeostasis is essential?
hoW it is achieved ?
2
3. The need for the existence of multiple
mechanisms, involved in Acid-Base
homeostasis is important for the hydrogen
ion (H + ) concentration which is essential
for the operation of many cellular enzymes
and function of vital organs, most
prominently the brain and the heart
3
4. Acid-Base homeostasis involves chemical
and physiologic processes responsible for
the maintenance of the acidity of body fluids
at levels that allow optimal function of the
whole individual
4
5. The chemical processes represent the
first line of defense to an acid or base load
and include the extracellular and
intracellular buffers.
The physiologic processes modulate
acid-base composition by changes in cellular
metabolism and by adaptive responses in the
excretion of volatile acids by the lungs and
fixed acids by the kidneys
3
6. The task imposed on the mechanisms that
maintain Acid-Base homeostasis is large.
◦ Metabolic pathways are continuously
consuming or producing H +
◦ The daily load of waste products for
excretion in the form of volatile and fixed
acids is substantial.
6
7. Acid- Base balance is primarily
concerned with two ions:
◦ Hydrogen (H + )
◦ Bicarbonate (HCO 3 - )
H +
HCO 3 7
8. H+ ion has special
significance
because of the
narrow ranges that
it must be
maintained in order
to be compatible
with living systems
8
10. Maintenance of an acceptable pH range in
the extracellular fluids is accomplished by
three mechanisms:
◦ 1) Chemical Buffers
React very rapidly
(less than a second)
◦ 2) Respiratory Regulation
Reacts rapidly (seconds to minutes)
◦ 3) Renal Regulation
Reacts slowly (minutes to hours)
10
11. What is acid ?
What are physiologically
important acids?
What is base?
What are physiologically
important bases?
11
12. Acids can be defined as a proton (H + ) donor
Many other substance (carbohydrates) also
contain hydrogen but they are not acids
because the hydrogen is tightly bound and it is
never liberated as free H +
Physiologically important acids include:
◦ Carbonic acid (H 2 CO 3 )
◦ Phosphoric acid (H 3 PO 4 )
◦ Pyruvic acid (C 3 H 4 O 3 )
◦ Lactic acid (C 3 H 6 O 3 )
12
13. Bases can be defined as:
◦ A proton (H + ) acceptor
◦ Give up OH- in solution.
◦ Physiologically important bases include:
◦ Bicarbonate (HCO 3 - )
◦ Biphosphate (HPO 4 -2 )
13
15. What is ph?
What is normal blood ph ?
What is the ph range
compatible With life?
15
16. pH refers to P otential H ydrogen
Expresses hydrogen ion concentration in water
solutions.
Water ionizes to form equal amounts of H + ions and
OH - ions
◦ H 2O H + + OH -
Pure water is Neutral ( H + = OH - )
pH = 7
Acid ( H + > OH - )
pH < 7
Base ( H + < OH - )
pH > 7
Normal blood pH is 7.35 - 7.45
pH range compatible with life is 6.8 - 8.0
◦
16
17. ThepH of the solution is defined as the
negative logarithm ( base 10 )of the
hydrogen ion (H + ) concentration
pH = log 1 / H + concentration
H+
concentration in extracellular fluid
(ECF)
4 X 10 -8 (0.00000004)
17
18. Low pH values = high H + concentrations
◦ H + concentration in denominator of formula
pH = log 1 / H + concentration
Unit changes in pH represent a tenfold
change in H + concentrations
18
19. pH = 4 is more acidic than pH = 6
pH = 4 has 10 times more free H +
concentration than pH = 5 and 100 times
more free H + concentration than pH = 6
ACIDOSIS NORMAL ALKALOSIS
DEATH DEATH
6.8 7.3 7.4 7.5 8.0
Venou Arteria
s l Blood
Blood 19
20. What is normal ratio o f HCO 3 -
to H 2 CO 3 ?
What is acidosis ?
What is alkalosis?
What is compensation ?
What are the effects of ph
change on cell functions?
20
21. BASE ACID
Normal ratio of HCO 3 - to H 2 CO 3 is 20:1
◦ H 2 CO 3 is source of H + ions in the body
Deviations from this ratio are used to identify Acid-
Base imbalances
H +
H 2 CO
HCO 3 21
22. An increase in the normal 20:1 base to
acid ratio so there is
◦ A decrease in the number of hydrogen
ions(ex: ratio of 20:0.5)
An increase in the number of bicarbonate
ions (ex: ratio of 40:1)
Caused by base excess or acid deficit
ACI BAS
22
23. Acidosis is a decrease in pH below 7.35
◦ Which means a relative increase of H +
ions.
◦ A relative decrease in HCO 3 -
◦ Both lead to a decrease in the ratio of
20:1
H +
= p
23
24. 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.
24
25. If underlying problem is metabolic,
hyperventilation or hypoventilation
can help by respiratory
compensation.
If problem is respiratory, renal
mechanisms can bring about normal
pH--- metabolic compensation .
25
26. pH changes have dramatic effects on
normal cell function
◦ 1) Changes in excitability of nerve and
muscle cells
◦ 2) Influences enzyme activity
◦ 3) Influences K + levels
26
27. pH decrease (more acidic) depresses the
central nervous system
◦ Can lead to loss of consciousness
pH increase (more basic) can cause over-
excitability
◦ Tingling sensations, nervousness,
muscle twitches
27
28. pH increases or decreases can alter the
shape of the enzyme rendering it non-
functional
Changes in enzyme structure can result in
accelerated or depressed metabolic actions
within the cell
28
29. When reabsorbing Na + from the filtrate of
the renal tubules K + or H + is secreted
(exchanged)
Normally K + is
secreted in much
greater amounts
than H +
K+ Na +
H+
K+
29
30. IfH + concentrations are high (acidosis) than
H + is secreted in greater amounts
This leaves less K + than usual excreted
The resultant K + retention can affect cardiac
function and other systems
K+ Na +
H+
30
31. What are the different types
of acidosis & alkalosis?
31
32. Deviations from normal Acid-Base status are
divided into four general categories,
depending on the source and direction of
the abnormal change in H + concentrations
◦ Respiratory Acidosis
◦ Respiratory Alkalosis
◦ Metabolic Acidosis
◦ Metabolic Alkalosis
32
33. ◦ Respiratory Acidosis and Respiratory
Alkalosis
◦ caused primarily by lung or breathing
disorders.
◦ Metabolic Acidosis and Metabolic
Alkalosis
caused by an imbalance in the production
and excretion of acids or bases by the
kidneys.
33
36. Caused by hypercapnia( CO2) due to
Hypoventilation
Or Increased CO2 production
Characterized by a decrease pH and an
increase in CO2
High levels of CO in the blood stimulate the
2
parts of the brain that regulate breathing, which
leads to faster and deeper breathing.
36
37. Decreased CO 2 removal can be the result
of:
1) Obstruction of air passages
2) Decreased respiration (depression of
respiratory centers)
3) Decreased gas exchange between
pulmonary capillaries and air sacs of
lungs (emphycema,bronchitis)
4) Collapse of lung
37
38. Etiology :1) Alveolar hypoventilation
Emphysema,
Chronic bronchitis,
Severe pneumonia
Pulmonary edema
Asthma
Flail chest
Diseases of the nerves or muscles of the chest .
Over sedation from narcotics and strong sleeping
medications .
38
39. 2) Increased CO2 production
Malignant hyperthermia
Thyroid storm
Intensive shivering
Prolonged seijures
39
40. 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
40
41. Treat the under lying cause
The treatment of respiratory acidosis aims to
improve the function of the lungs.
Drugs to improve breathing may help people who
have lung diseases such as asthma and
emphysema.
Ventilatory support.
41
42. -metabolic balance before onset
of acidosis
-pH = 7.4
-respiratory acidosis
-pH = 7.1
-breathing is suppressed holding
CO 2 in body
-body’s compensation
-kidneys conserve HCO 3 - ions to
restore the normal 40:2 ratio
-kidneys eliminate H + ion in acidic
urine
- therapy required to restore
metabolic balance
40
- lactate solution used in therapy
is converted to bicarbonate ions in
the liver 42
44. Cause is Hyperventilation leads to
elimination of excessive amounts of CO 2.
◦ Increased loss of CO 2 from the lungs at
a rate faster than it is produced.
◦ There is increase in pH and decrease in
H+
44
45. Can be the result of:
◦ 1) pain,anxiety, emotional
disturbances
◦ 2) Respiratory center lesions
◦ 3) Fever
◦ 4) Salicylate poisoning (overdose)
◦ 5) Assisted respiration
◦ 6) High altitude (low P O 2 )
45
46. Kidneys compensate by:
Retaining hydrogen ions
Increasing bicarbonate excretion
Respiratory system
Decreased CO 2 in the lungs will
eventually slow the rate of
breathing
Will permit a normal amount of CO 2
to be retained in theHHCO
H
lung
+ +
-
3
HCO 3 - H
+
H + HCO 3
-
HCO 3 - H+
HCO 3 -
H +
HCO - H
+
3
H+
46
47. Usually the only treatment needed is to slow
down the rate of breathing
Breathing into a paper bag or holding the
breath as long as possible may help raise
the blood CO 2 content as the person
breathes carbon dioxide
back in after breathing it out
47
48. -metabolic balance before
onset of alkalosis
-pH = 7.4
-respiratory alkalosis
-pH = 7.7
- hyperactive breathing “ blows
off ” CO 2
- body’s compensation
- kidneys conserve H + ions and
eliminate HCO 3 - in alkaline urine
- therapy required to restore
metabolic balance
- HCO 3 - ions replaced by Cl - ions
48
49. What is metabolic
acidosis (mac) ?
What are the different
causes of mac ?
What is the treatment of
mac ?
49
50. Decrease in blood pH and bicarbonate level
(below 22mEq/L)
Excessive H + or decreased HCO -
3
H 2 CO CO 3
HHCO 3
O
H32C
= 7.4
= 7.4
--
3
1 : 10
20 50
51. The causes of metabolic acidosis can be
grouped into five major categories
◦ 1) Ingesting an acid (acetylsalicylic acid)
◦ 2) Abnormal Metabolism (type I
DM,shock)
◦ 3) Kidney Insufficiencies(renal tubular
acidosis or uremic acidosis )
◦ 4) Strenuous Exercise
◦ 5) Severe Diarrhea
51
52. Unregulated diabetes
mellitus causes
ketoacidosis
◦ Body metabolizes fat
rather than glucose
◦ Accumulations of
metabolic acids
(Keto Acids) cause
an increase in plasma
H+
52
53. This leads to excessive production of
ketones:
◦ Acetone
◦ Acetoacetic acid
◦ B-hydroxybutyric acid
Contribute excessive numbers of hydrogen
ions to body fluids
Acetone
H + H+
Acetoacetic
H+ H+ H+
acid
Hydroxybutyric
H
acid+ + 53
54. As the blood pH drops,
breathing becomes
deeper and faster as the
body attempts to rid the
blood of excess acid by
decreasing the amount
of carbon dioxide
54
55. Eventually, the kidneys
also try to compensate by
excreting more acid in the
urine
However, both
mechanisms can be
overwhelmed if the body
continues to produce too
much acid, leading to
severe acidosis and
eventually a coma
55
56. ◦ If the acidosis is mild, intravenous fluids and
treatment for the underlying disorder may be all
that's needed.
◦ control diabetes with insulin or treat poisoning by
removing the toxic substance.
When acidosis is severe, bicarbonate may be
given
(NaHCO3=BD X 30% X BODY WEIGHT
◦ Bicarbonate provides only temporary relief and
may cause harm.
56
57. - metabolic balance before
onset of acidosis
- pH 7.4
- metabolic acidosis
- pH 7.1
- HCO 3 - decreases because of
excess presence of ketones,
chloride or organic ions
- body’s compensation
- hyperactive breathing to “
blow off ” CO 2
- kidneys conserve HCO 3 - and
eliminate H + ions in acidic urine
- therapy required to restore
metabolic balance
- lactate solution used in therapy
0.5 10 is
converted to bicarbonate ions
57
58. What is anion gap ?
What is the normal value?
What is the effect of albumin?
58
59. To achieve electrochemical balance, the concentration
of negatively-charged anions must equal the
concentration of positively-charged cations.
Na+UC=(Cl+HCO3)+UA
Rearranging: Na-(Cl+HCO3)=UA-UC
The difference (UA - UC) is a measure of the relative
abundance of unmeasured anions
and is called the anion gap (AG).
The normal value of the AG was originally set at 12 ± 4
mEq/L (range = 8 to 16 mEq/L)
59
60. Unmeasured Anions Unmeasured
Cations
Albumin (15 mEq/L)* Calcium (5 mEq/L)
Organic Acids (5 mEq/L) Potassium (4.5 mEq/L)
Phosphate (2 mEq/L) Magnesium (1.5 mEq/L)
Sulfate (1 mEq/L)
Total UA: (23 mEq/L) Total UC: (11 mEq/L)
Anion Gap = UA - UC = 12 mEq/L
*If albumin is reduced by 50%, anion gap = 4 mEq/L
60
61. Increased anion gap Normal anion gap
(hyperchloremic)
Renal failure Increased HCO3 loss by GIT
Ketoacdosis (DM,starvation) Diarrhea, fistula,
ureterosigmoidostomy
Lactic acidosis Increased loss of HCO3 by kidneys
Ingestion of toxin-salicylate methanol, Renal tubular
ethylene glycol acidosis,hypoaldosteronism
rabdomyolysis Dilutional –large amt of HCO3 free
fluids
61
62. What is metabolic
alkalosis (mal) ?
What are the different
causes of mal ?
What is the treatment of
mal ?
62
63. Elevation of pH due to an increased 20:1
ratio
◦ May be caused by:
An increase of bicarbonate
A decrease in hydrogen ions
◦ Imbalance again cannot be due to CO 2
◦ Increase in pH which has a non-respiratory
origin
63
64. Can be the result of:
1) Ingestion of Alkaline Substances (NaHCO 3 ) often used as a
remedy for gastric hyperacidity.
◦ 2)Vomiting ,gastric drainage( loss of HCl )
◦ 3)certain diuretics
◦ 4)endocrine disorders:
◦ prim. hyperaldosteronism, cushing synd.
◦ 5)massive blood transfusion
◦ 6)severe dehydration
64
65. Reaction of the body to alkalosis is to lower
pH by:
◦ Retain CO 2 by decreasing breathing rate.
◦ Kidneys increase the retention of H +
H+
H+
CO H+
CO 2 H+
2
65
66. Treatment of metabolic alkalosis is most
often accomplished by replacing water and
electrolytes (sodium and potassium)
potassium
while treating the underlying cause
Occasionally when metabolic alkalosis is
very severe, dilute acid in the form of
ammonium chloride is given by IV
66
67. - metabolic balance before onset
of alkalosis
- pH = 7.4
- metabolic alkalosis
- pH = 7.7
- HCO 3 - increases because of
loss of chloride ions or excess
ingestion of NaHCO 3
- body’s compensation
- breathing suppressed to hold
CO 2
- kidneys conserve H + ions and
eliminate HCO 3 - in alkaline urine
- therapy required to restore
metabolic balance
1.2 25 - HCO 3 - ions replaced by Cl - ions
5
67
69. RESP RESP METAB METAB
ACIDOSIS ALKALOSI ACIDOSIS ALKALOSIS
S
COMPENSAT Kidneys Kidneys Increased Alkalosis
ION eliminate conserve ventilation commonly
hydrogen ion hydrogen ion Renal occurs with
and retain Excrete excretion of H renal
bicarbonate bicarbonate ions. dysfunction,
ion ion K+ exchanges so can’t count
with excess H+ on kidneys.
in ECF Respiratory
( H+ into cells, compensation
K+ out of cells) difficult –
hypoventilatio
n limited by
hypoxia
TREATMENT Restore Breathe into IV lactate Electrolytes to
ventilation, a paper bag solution replace those
IV lactate IV Chloride lost,
solution containing IV chloride 69
70. disturbance response Expected changes
Respiratory acidosis
acute HCO3 1mEq/L/10 mm of Hg inc
.in Paco2
chronic HCO3 4mEq/L/10 mm of Hg inc
.in Paco2
Respiratory alkalosis
acute HCO3 2mEq/L/10 mm of Hg
dec .in Paco2
chronic HCO3 4mEq/L/10 mm of Hg
dec .in Paco2
Metabolic acidosis PPaco2 1.2 x the decrease in
HCO3
Metabolic alkalosis Paco2 0.7 x the increase in
HCO3 70
71. Mechanisms protect the body against life-
threatening changes in hydrogen ion
concentration
◦ 1) Buffering Systems in Body
Fluids
◦ 2) Respiratory Responses
◦ 3) Renal Responses
◦ 4) Intracellular Shifts of Ions
71
72. Buffering systems provide an immediate
response to fluctuations in pH
◦ 1) Phosphate
◦ 2) Protein
◦ 3) Bicarbonate Buffer System
A buffer is a combination of chemicals in
solution that resists any significant change
in pH
Able to bind or release free H + ions
72
73. 1) Phosphate buffer system
Na 2 HPO 4 + H + NaH 2 PO 4 + Na +
Most important in the intracellular system.
Phosphate concentrations are higher
intracellularly and within the kidney tubules.
73
74. 2) Protein Buffer System
◦ Behaves as a buffer in both plasma and
cells.
◦ Hemoglobin is by far the most important
protein buffer.
Proteinsare excellent buffers because they
contain both acid and base groups that can
give up or take up H +
74
75. As H + Hb picks up O 2 from the lungs the Hb
which has a higher affinity for O 2 releases H +
and picks up O 2
Liberated H + combines with HCO -
3
HCO 3 - H 2 CO 3 CO 2 (exhaled)
O2 H+
H
O2 O2
b 75
76. Protein
buffer system works instantaneously
making it the most powerful in the body.
75% of the body’s buffer capacity is
controlled by protein.
◦ Bicarbonate and phosphate buffer systems
require several hours to be effective
76
77. 3) Bicarbonate Buffer System
◦ Predominates in extracellular fluid (ECF)
ECF
HCO 3 - + H + H 2 CO 3
This system is most important
because the concentration of
both components can be
regulated:
◦Carbonic acid by the
respiratory system
◦Bicarbonate by the renal
system
77
78. Neurons in the medulla oblongata and pons
constitute the Respiratory Center
Increases in CO and H +
2
stimulate the
respiratory center.
◦ The effect is to
raise respiration
rates, but the effect
diminishes in Respiratory
1 - 2 minutes. centers
78
79. Chemoreceptors are also present in the
carotid and aortic arteries which respond to
changes in partial pressures of O 2 and CO 2
or pH
Increased levels of
CO 2 (low pH) or
pH
decreased levels of
O 2 stimulate
respiration rates
to increase
79
80. Overallcompensatory response is:
◦ Hyperventilation in response to
increased CO 2 or H + (low pH)
pH
◦ Hypoventilation in response to
decreased CO 2 or H + (high pH)
pH
80
81. cell production of CO 2 increases
CO 2 + H 2 O H 2 CO 3
H 2 CO 3 H + + HCO 3 -
H+ acidosis; pH drops
H + stimulates respiratory center in medulla oblongata
rate and depth of breathing increase
CO 2 eliminated in lungs
pH rises toward normal
81
82. The kidney compensates for Acid - Base
imbalance within 24 hours and is
responsible for long term control
The kidney in response:
◦ To Acidosis
Retains bicarbonate ions and eliminates
hydrogen ions
◦ To Alkalosis
Eliminates bicarbonate ions and retains
hydrogen ions
82
83. CO 2 + H 2 O H 2 CO 3 H + + HCO 3
yperventilation removes Kidneys eliminate or retai
H + ion concentrations H + or bicarbonate ions
ypoventilation increases
H + ion concentrations
83
84. Hyperkalemia is generally associated with
acidosis
◦ Accompanied by a shift of H + ions into cells
and K + ions out of the cell to maintain
electrical neutrality.
◦ Acidosis may cause Hyperkalemia and
Hyperkalemia may cause Acidosis
H +
K +
84
85. Hypokalemia is generally associated with
reciprocal exchanges of H + and K + in the
opposite direction
◦ Associated with alkalosis
H +
K +
85
