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Acid-Base Physiology
 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
4
ACIDS
5
ACIDS
 An acid is a substance that can release
or donate H+
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)
BASES
 a base is a substance that can combine
with or accept H.
8
BASES
 Physiologically important bases include:
– Bicarbonate (HCO3
- )
– Biphosphate (HPO4
-2 )
Biphosphate
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]
1
10000000
=
10
-7
=
0.00000001
10
pH
=
[H +]
- Log
10
=
pH [H +]
pH = - log [H+ concentration]
0.00000001
Log
10
=
-7 X-1
X-1 -
7
10
-1
pH value
1
10
-2
2
10
-3
3
10
-4
4
10
-5
5
10
-6
6
tenfold
Unit changes in pH represent a tenfold
 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
acidosis Alkalosis
1 14
7.4
PH
 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
 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
 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
Nerve & muscle
Na+
Na+
Na+
EXCITABILITY
Ca+ 2
Ca+ 2
Ca+ 2
Ca+ 2
H+
H+ Ca+ 2
Albumin
H+
H+
Acidosis
Na+
Na+
Nerve & muscle
EXCITABILITY
Na+
H+
Na+
Na+
Ca+ 2
Ca+ 2
Ca+ 2
H+
H+ Ca+ 2
Albumin
alkalosis
19
INFLUENCES ON ENZYME ACTIVITY
pH increases or decreases can alter the
shape of the enzyme rendering it non-
functional
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
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
 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)
Acid-Base Balance
Chemical Buffers
Respiratory mechanism
Renal Regulation
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
pH =7
7
14
acid
4
buffer
9
14
6
HENDERSON-HASSELBALCH EQUATION
 HB ↔ H + B
 Ka = [H] [B]
HB
 [H] = Ka [HB]
[B]
 -log[H] = - log ka –log [HB]
[B]
PH = pK + Log [B]
[HB]
[ka > 1 (strong) …. ka < 1 (weak)
]
7.4 = 6.1 + Log [HCO3
-]
[H2CO3]
PH = pK + Log [B]
[HB]
HCO3
-/H2CO3 Buffer
HPO4
-2/H2PO4 Buffer
7.4 = 6.8 + Log [HPO4
-2]
[H2PO4]
ICF
ECF
H2CO3/HCO3
Hb
Plasma
protein
phospate
protein
HCO3
NH3
Phosphate
Renal Mechanisms in
Acid-Base Balance
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+.
Reabsorption of HCO3
 Almost 99.9% of the filtered HCO3
- is
reabsorbed
 Purpose :- important extracellular buffer
HCO3
- is not excreted in urine
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
HCO3
-
H+
Na+
CO2
H2O
H+ HCO3
-
HCO3
-
H+
Na+
Alkalosis
HCO3
-
HCO3
-
HCO3
-
 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
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
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
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
H+
H+
H+
H+
H+
H+
pH is 4.4
H+
H+
H+
H+ concentrationgradient active transport
 Three important reactions in the
tubular fluid
 HCO3- + H+ → H2CO3 “weak acid”
 HPO4
-2 + H+ = H2PO4
- “weak acid”
 NH3 + H+ = NH4 “weak acid”
Fate of H+ in the Urine
H+
H+
H+
H+
H+
H+
pH is 4.4
H+
H+
H+
Buffer
Weak acid
α-intercalated cells
H+ - K
ATPase
H+
K+
CO2
+
H2O
H2CO3
H+
HCO3-
HPO4
-2
+
H2PO4
-
Principle cell
H+ ATPase
H+
CO2
+
H2O
H2CO3
H+
HCO3-
HPO4
-2
+
H2PO4
-
Glutamine = NH3 +α-ketoglutarate
NH3
H+
+
NH4
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
ACIDOSIS / ALKALOSIS
 Acidosis :- disorders that cause a decrease
in the blood pH
 Alkalosis :- disorders that cause an
increase in the blood pH
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
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
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
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
ACIDOSIS / ALKALOSIS
 Deviations from normal Acid-Base status are
divided into four general categories:-
– Respiratory Acidosis
– Respiratory Alkalosis
– Metabolic Acidosis
– Metabolic Alkalosis
Acid-Base status
Pulmonary Origin
None Pulmonary Origin
Deviations
Respiratory
Acidosis
Alkalosis
metabolic
Acidosis
Alkalosis
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
54
RESPIRATORY ACIDOSIS
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
56
HYPOVENTILATION
Elimination of CO2
H+
pH
RESPIRATORY ACIDOSIS
 hyperkapnia due to
 emphysema
 chronic bronchitis
 severe pneumonia
 pulmonary edema
 asthma
57
58
RESPIRATORY ACIDOSIS
- metabolic balance before onset of acidosis
- pH = 7.4
H2CO3 HCO3
-
1 20
:
H2CO3 : Carbonic Acid
HCO3
- : Bicarbonate Ion
59
RESPIRATORY ACIDOSIS
-breathing is suppressed holding CO2 in body
-pH = 7.1
H2CO3
2 20
:
CO2
CO2
CO2
CO2
60
RESPIRATORY ACIDOSIS
BODY’S COMPENSATION
-kidneys conserve HCO3
- ions to restore the
normal 40:2 ratio (20:1)
-kidneys eliminate H+ ion in acidic urine
2 40
:
HCO3
-
H2CO3
H+
acidic urine
H2CO3
61
RESPIRATORY ALKALOSIS
62
RESPIRATORY ALKALOSIS
 Normal 20:1 ratio is increased
– pH of blood is above 7.4
0.5 20
:
= 7.4
H2CO3
1
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
64
HYPERVENTILATION
Elimination of CO2
H+
pH
65
RESPIRATORY ALKALOSIS
 Can be the result of:
– 1) Anxiety, emotional
disturbances
– 2) Respiratory center lesions
– 3) Fever
– 4) Salicylate poisoning
(overdose)
– 5) High altitude (low PO2)
66
RESPIRATORY ALKALOSIS

Kidneys compensate by:
–
Retaining hydrogen ions
–
Increasing bicarbonate excretion
H+
HCO3
-
HCO3
-
HCO3
-
HCO3
-
HCO3
-
HCO3
-
HCO3
-
HCO3
-
HCO3
-
HCO3
-
H+
H+
H+
H+
H+
H+
H+
H+
H+
H+
67
RESPIRATORY ALKALOSIS
-respiratory alkalosis
-pH = 7.7
-hyperactive breathing “ blows off ” CO2
0.5 20
:
CO2
CO2 + H2O
H2CO3
68
RESPIRATORY ALKALOSIS
BODY’S COMPENSATION
- kidneys conserve H+ ions and eliminate HCO3
- in
alkaline urine
1 20
:
HCO3
-
Alkaline Urine
69
METABOLIC ACIDOSIS
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
71
METABOLIC ACIDOSIS
-HCO3
- decreases because of excess presence of
ketones
-pH 7.1
1 10
:
= 7.4
H2CO3
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
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
electroneutrality
Na+
CL-
HCO3
-
140 mEq/L
105 mEq/L
24 mEq/L
anion gap
11 mEq/L
Anion gap = Na – [CL- + HCO3-]
electroneutrality
Na+
anion gap
Metabolic acidosis
Fixed acid
 Ketoacid + H+
 Lactate + H+
 Formate + H+
HCO3
-
CL-
Metabolic acidosis with a high anion gap
organic anion
electroneutrality
Na+
anion gap
Metabolic acidosis
Non organic anion
 Diarrhoea
(Loss HCO3-)
 renal tubular
acidosis
(H+ retention)
HCO3
-
CL-
hyperchloremic Metabolic acidosis with a normal anion gap
77
METABOLIC ALKALOSIS
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
METABOLIC ALKALOSIS
 Can be the result of:
– 1) Ingestion of Alkaline Substances
– 2) Vomiting ( loss of HCl )
80
METABOLIC ALKALOSIS
BODY’S COMPENSATION
- kidneys conserve H+ ions and eliminate HCO3
- in
alkaline urine
CO2
+ H2O
HCO3
- + H+
HCO3
-
H+
+
Alkaline urine
:
5-Acid-Base Physiology .ppt

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5-Acid-Base Physiology .ppt