3. Introduction about (acid & base)
General overview about pH
Effects of pH on normal cell function
Regulation (Acid-Base Balance)
Renal Mechanisms in Acid-Base Balance
Henderson-hasselbalch equation
Acidosis / alkalosis
Acid-Base Physiology
6. Acid Production in the Body
Fixed acid Volatile acid
catabolism
Protein
sulfuric acid
phospholipids
Phosphoric acid
Pathophysiologic
states
ketoacids
ingested
salicylic acid
formic acid
(carbon dioxide)
7. BASES
a base is a substance that can combine
with or accept H.
9. pH
The hydrogen ion (H+) concentration of the
body fluids is extremely low
In arterial blood, the H+ concentration is 4 ×
10-8 equivalents per liter (or 40 nEq/L),
difficult to work with such small numbers
H+ concentration is routinely expressed as a
logarithmic function called pH
4 X 10 -8 (0.00000004)
pH = - log [H+ concentration]
12. 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
pH
14. H+ concentration increases, pH decreases
H+ concentration decreases, pH increases
Normal blood pH is 7.37 - 7.42 (average 7.4)
is essential for all cellular functions
pH is less than 7.37, it is called Acidosis.
pH is greater than 7.42, it is called alkalosis
pH range compatible with life is 6.8 - 8.0
pH
ACIDOSIS ALKALOSIS
NORMAL
7.37 7.42
7.4
6.8 8.0
15. 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
pH
16. pH decrease (more acidic) depresses the
central nervous system
– Can lead to loss of consciousness
pH increase (more basic) can cause over-
excitability
– nervousness, muscle twitches
CHANGES IN CELL EXCITABILITY
19. 19
INFLUENCES ON ENZYME ACTIVITY
pH increases or decreases can alter the
shape of the enzyme rendering it non-
functional
20. 20
INFLUENCES ON K+ LEVELS
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+
K+
K+
K+
K+
K+
K+
Na+
Na+
Na+
Na+
Na+
Na+
H+
21. 21
INFLUENCES ON K+ LEVELS
If H+ 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+
K+
K+
Na+
Na+
Na+
Na+
Na+
Na+
H+
H+
H+
H+
H+
H+
H+
K+
K+
K+
K+
K+
22. 22
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 mechanism
Reacts rapidly (seconds to minutes)
that excrete carbon dioxide
– 3) Renal mechanism
Reacts slowly (minutes to hours)
reabsorb bicarbonate
secrete hydrogen ions
Regulation (Acid-Base Balance)
24. Buffer
ACID-BASE REGULATION
Chemical Buffers
Buffer – A buffer is substance that resists pH
changes when acids or bases are added to the
solution. Example
HCO3
-/H2CO3 Buffer
HPO4
-2/H2PO4 Buffer
24
30. Renal Mechanisms in Acid-Base Balance
The kidneys play two major roles in the
maintenance of normal acid-base balance:
1. Reabsorption of HCO3
-
2. Excretion of H+.
31. Reabsorption of HCO3
Almost 99.9% of the filtered HCO3
- is
reabsorbed
Purpose :- important extracellular buffer
HCO3
- is not excreted in urine
32. amount of HCO3 enter
HCO3
[24 mEq/L,] 180 L/day
2 mEq/day
amount of HCO3 taken up Kidney /min
(filtered load 4320 mEq/day ) excretion rate of HCO3
35. The reabsorption rate can be calculated by comparing
the filtered load of HCO3
- with the excretion rate of
HCO3
-.
filtered load > excretion rate (Reabsorption)
filtered load = [P]HCO3 X GFR
filtered load of HCO3
- = 180 L/day × 24 mEq/L
= 4320 mEq/day
excretion rate of HCO3 = 2 mEq/day
The reabsorption rate = 4318 mEq/day, which is
99.9% of the filtered load
Reabsorption of HCO3
36. REABSORPTION OF FILTERED HCO3
-
Most filtered HCO3
- reabsorption occurs in the
proximal tubule.
Small quantities are reabsorbed in the loop of
Henle, distal tubule, and collecting duct
37. Mechanism of HCO3
- Reabsorption in
the Proximal Tubule
Reabsorption of filtered HCO3
- involves the
following steps:-
1. conversion of HCO3
- to CO2 in the lumen
2. diffusion of CO2 into the cell
3. conversion of CO2 back to HCO3
- in the cell,
4. reabsorption of HCO3
- into the blood
38. Excretion H+
H+ secretion in the PCT by Na–H exchange
H+ secretion in the CT as follow:-
Principal cell (P cell) is secreted by H+ ATPase.
intercalated cells (I cells) is secreted by H+-K+
ATPase
45. 45
ACIDOSIS / ALKALOSIS
An abnormality in one or more of the pH control
mechanisms can cause one of two major
disturbances in Acid-Base balance
– Acidosis
– Alkalosis
46. 46
ACIDOSIS / ALKALOSIS
Acidosis :- disorders that cause a decrease
in the blood pH
Alkalosis :- disorders that cause an
increase in the blood pH
47. ACIDOSIS / ALKALOSIS
Normal ratio of HCO3
- to H2CO3 is 20:1
Deviations from this ratio are used to identify
Acid-Base imbalances
47
BASE ACID
PH = pKa + Log [HCO3
- ]
[H2CO3]
7.4
48. 48
ACIDOSIS / ALKALOSIS
A pH of 7.4 corresponds to a 20:1 ratio of HCO3
-
and H2CO3
– Concentration of HCO3
- is 24 meq/liter and
H2CO3 is 1.2 meq/liter
Bicarbonate
Carbonic Acid
Bicarbonate
Bicarbonate
Bicarbonate
Bicarbonate
Bicarbonate
Bicarbonate
Bicarbonate
Bicarbonate
Bicarbonate
Bicarbonate
Bicarbonate
Bicarbonate
Bicarbonate
Bicarbonate
Bicarbonate
Bicarbonate
Bicarbonate
Bicarbonate
Bicarbonate
49. 49
ACIDOSIS
A decrease in a normal 20:1 base to
acid ratio
– An increase in the number of
hydrogen ions
(ex: ratio of 20:2 translated to 10:1)
– A decrease in the number of bicarbonate ions
(ex: ratio of 10:1)
Caused by too much acid or too little base
ACID BASE
50. 50
ALKALOSIS
An increase in the normal 20:1 base to acid ratio
– A decrease in the number of hydrogen ions
(ex: ratio of 20:0.5 translated to 40:1)
– An increase in the number of bicarbonate ions
(ex: ratio of 40:1)
Caused by base excess or acid deficit
ACID BASE
51. 51
ACIDOSIS / ALKALOSIS
Deviations from normal Acid-Base status are
divided into four general categories:-
– Respiratory Acidosis
– Respiratory Alkalosis
– Metabolic Acidosis
– Metabolic Alkalosis
53. ACIDOSIS / ALKALOSIS
Acidosis and Alkalosis are categorized as
Metabolic or Respiratory depending on their
primary cause
– Metabolic Acidosis and Metabolic
Alkalosis
This disturbance is not pulmonary origin
– Respiratory Acidosis and Respiratory
Alkalosis
caused primarily by lung or breathing
disorders
53
55. 55
RESPIRATORY ACIDOSIS
Caused by hyperkapnia due to
hypoventilation
– Characterized by a pH decrease and an
increase in CO2
CO2 CO2
CO2
CO2
CO2
CO2
CO2
CO2
CO2
CO
CO2 CO2
CO2
pH
pH
63. 63
RESPIRATORY ALKALOSIS
Cause is Hyperventilation
– Leads to eliminating excessive amounts of
CO2
– Increased loss of CO2 from the lungs at a
rate faster than it is produced
– Decrease in H+
CO2 CO2 CO2
CO2
CO2
CO2
CO2
CO2
CO2
CO2
CO2
CO2
70. 70
METABOLIC ACIDOSIS
The causes of metabolic acidosis can be
grouped into five major categories
– 1) Ingesting an acid or a substance that
is metabolized to acid
– 2) Abnormal Metabolism
– 3) Kidney Insufficiencies
– 4) Strenuous Exercise
– 5) Severe Diarrhea
72. 72
METABOLIC ACIDOSIS
BODY’S COMPENSATION
- hyperactive breathing to “ blow off ” CO2
- kidneys conserve HCO3
- and eliminate H+ ions in
acidic urine
:
CO2
CO2
+ H2O
HCO3
- + H+
HCO3
-
+
H+
Acidic urine
73. anion gap
The anion gap is based on the principle of
electroneutrality [±]
The sums of the positive and negative charges
are equal
Plasma (electroneutrality) [cations] = [anions]
anion gap :- range of 8 to 16 mEq/L.
73
78. 78
METABOLIC ALKALOSIS
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 CO2
– Increase in pH which has a non-
respiratory origin
7.4
79. 79
METABOLIC ALKALOSIS
Can be the result of:
– 1) Ingestion of Alkaline Substances
– 2) Vomiting ( loss of HCl )