Acid-Base Status

Q. Define pH and mention 2 disturbance of pH

1 pH = log -------[H+]

As H+ ion concentration increases, pH decrease (more acidic) and Vice versa. Each unit change in pH leads 10 fold change in H+.

pH: arterial blood = 7.4 Venous blood = 7.35 Venous blood is acidic than arterial blood, because acids are added to venous blood. If pH of arterial blood below 7.4 = acidosis If pH of arterial blood above 7.4 = alkalosis. Below pH (6.8) or above (8) death occurs.

pH SCALE

pH equals the logarithm (log) to the base 10

of the reciprocal of the hydrogen ion (H+) concentration pH = log 1 / H+ concentration

H+ concentration in extracellular fluid (ECF)

4 X 10 -8 (0.00000004)
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pH SCALE

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 DEATH 6.8 7.3 Venous Blood 7.4 7.5 Arterial Blood
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NORMAL

ALKALOSIS DEATH 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

CHANGES IN CELL EXCITABILITY

pH decrease (more acidic) depresses the

central nervous system Can lead to loss of consciousness pH increase (more basic) can cause overexcitability Tingling sensations, nervousness, muscle twitches

The most general effect of pH changes are

on enzyme function Also affect excitability of nerve and muscle cells

pH & Excitability

pH
pH

Excitability
Excitability
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INFLUENCES ON ENZYME ACTIVITY

pH increases or decreases can alter the

shape of the enzyme rendering it nonfunctional Changes in enzyme structure can result in accelerated or depressed metabolic actions within the cell

ELECTROLYTE SHIFTS
Acidosis
Compensatory Response
H+ K+ cell

Result - H+ buffered intracellularly - Hyperkalemia

Alkalosis
Compensatory Response
H+
K+ cell
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Result

- Tendency to correct alkalosis - Hypokalemia

Q. What is the different Sources of H+ in the body. 1) Carbonic acid formation (volatile acid): cellular carbonic anhydrase CO2 + H2O H2CO3 2) Inorganic acids (non volatile) produced during
break down of nutrients. 3) Organic acids: Resulting from intermediary metabolism e.g: fatty acids, lactic acid (during exercise). N.B. More acid produced than bases in body.
oxidation

Physiologically important acids include: Carbonic acid (H2CO3) Phosphoric acid (H3PO4) Pyruvic acid (C3H4O3) Lactic acid (C3H6O3) These acids are dissolved in body fluids
Lactic acid Pyruvic acid Phosphoric acid

ACIDS

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ACID-BASE REGULATION

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)
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This system is most

BICARBONATE BUFFER SYSTEM

important because the concentration of both components can be regulated: Carbonic acid by the respiratory system Bicarbonate by the renal system

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Regulates pH within the cells and the urine Phosphate concentrations are higher
intracellularly and within the kidney tubules Too low of a concentration in extracellular fluid to have much -2 HPO4 importance as an ICF buffer system
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PHOSPHATE BUFFER SYSTEM

PHOSPHATE BUFFER SYSTEM

Phosphate buffer system

Na2HPO4 + H+

Most important in the intracellular system

+Na2HPO4 +Na+ NaH2PO4
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NaH2PO4 + Na+

H+
Click to animate

 Protein Buffer System Behaves as a buffer in both plasma and

cells Hemoglobin is by far the most important protein buffer

PROTEIN BUFFER SYSTEM

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PROTEIN BUFFER SYSTEM

Most important
intracellular buffer (ICF) The most plentiful buffer of the body

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Proteins are excellent buffers because they

contain both acid and base groups that can give up or take up H+ Proteins are extremely abundant in the cell The more limited number of proteins in the plasma reinforce the bicarbonate system in the ECF

PROTEIN BUFFER SYSTEM

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H+ generated at the tissue level from the

dissociation of H2CO3 produced by the addition of CO2 Bound H+ to Hb (Hemoglobin) does not contribute to the acidity of blood
O2 O2

PROTEIN BUFFER SYSTEM

Hb
O2 O2
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As H+Hb picks up O2 from the lungs the Hb

which has a higher affinity for O2 releases H+ and picks up O2 Liberated H+ from H2O combines with HCO3-

PROTEIN BUFFER SYSTEM

HCO3O2

H2CO3
H+

CO2 (exhaled)

Hb
O2 O2
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Venous blood is only slightly more acidic

than arterial blood because of the tremendous buffering capacity of Hb Even in spite of the large volume of H+ generating CO2 carried in venous blood

PROTEIN BUFFER SYSTEM

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Proteins are very large, complex molecules

PROTEIN BUFFER SYSTEM

in comparison to the size and complexities of acids or bases Proteins are surrounded by a multitude of negative charges on the outside and numerous positive charges in the crevices of the molecule - - -+ + - + - - - + ++ + - - - ++ + + + + -- + + + + +++ + + + + + - - - - - - - 27

H+ ions are attracted to and held from

H+ H+ H+ H+ H+ H+ H+

PROTEIN BUFFER SYSTEM

chemical interaction by the negative charges

H+ H+

H+

H+

+ ++ ++ + - - - ++ + + + + -- + + - + + +++ + + + + + - - - - - - - H+
H+ H+ H+

- - -+

- - --

H+

H+

H+

H+

H+
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H+

OH- ions which are the basis of alkalosis are

attracted by the positive charges in the crevices of the protein
OHOHOHOH-

PROTEIN BUFFER SYSTEM

OH-

OH-

OH-

+ ++ ++ + - - - ++ + + + + -- + + - + + +++ + + + + + - - - - - - - OH-

- - -+

- - --

OH-

OH-

OH-

OH-

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PROTEIN BUFFER SYSTEM

H+
H+ OH-

H+ OH-

H+

OH-

H+

H+

OH- H+

OHH+ H+

HOH+

H+ OH-

+ ++ ++ + - - - ++ + + + + -- + + - + + +++ + + + + + - - - - - - - OHH+ H+ OHH+

- - -+

- - --

OH-

H+

H+ OHH+
+OH H

H+

H+

H+

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RESPIRATORY CONTROL OF pH
cell production of CO2 increases CO2 + H2O H2CO3

H2CO3 H+

H+ + HCO3acidosis; pH drops

H+ stimulates respiratory center in medulla oblongata

rate and depth of breathing increase

CO2 eliminated in lungs

pH rises toward normal

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Chemosensitive areas of the respiratory

center are able to detect blood concentration levels of CO2 and H+ Increases in CO2 and H+ stimulate the respiratory center The effect is to raise respiration rates But the effect diminishes in 1 - 2 minutes
Click to increase CO2
CO2 CO2 CO CO22 CO2 CO2 CO2 CO
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CHEMOSENSITIVE AREAS

Overall compensatory response is: Hyperventilation in response to

increased CO2 or H+ (low pH) Hypoventilation in response to decreased CO2 or H+ (high pH)

SO

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Renal Regulation Of pH
The kidney regulate pH by:-

1. Reabsorption of filtered HCO3. 2. Generation of new HCO3 . 3. H secretion.

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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
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RENAL RESPONSE

Reabsorption of filtered HCO3

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HCO3 production & H+ Secretion By Proximal Renal Epithelial Cell

Proximal tubular cell CO2+H2O oCA H2CO3 l m
HCO3-

Na+

Peritubular Capillaries

Na+
HCO3-

HCO3-

H+

H+ Na+ H+
HCO3-

Na+

Na+

H2CO3

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HCO3 production & H+ Secretion By distal Renal Epithelial Cell

Distal tubular cell
Peritubular Capillaries

HCO3-

CO2+H2O oCA H2CO3 l m

HCO3-

H+ H+ H+ H+

H+

H- pump

Cl-

ClH+

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Renal tubular H+ buffering

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Factors affecting acid (H secretion in the kidney)

1- PCO2: When PCO2 is high (respiratory acidosis), more intracellular HCO3- is available and vice versa. 2- K+ concentration: When it increases, H+ secretion decreases since both compete for secretion in DCT

& CCDs.
3- Carbonic anhydrase: When carbonic anhydrase is inhibited, acid secretion is inhibited. 4- Aldosterone: enhances tubular reabsorbtion of Na + and increases K+ and H+ secretion.
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ACIDOSIS / ALKALOSIS

Acidosis

A condition in which the blood has too

much acid (or too little base), frequently resulting in a decrease in blood pH

Alkalosis

A condition in which the blood has too

much base (or too little acid), occasionally resulting in an increase in blood pH
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ACIDOSIS / ALKALOSIS

Normal ratio of HCO3- to H2CO3 is 20:1 H2CO3 is source of H+ ions in the body Deviations from this ratio are used to identify AcidBase imbalances

BASE

ACID

H2CO3

+ H HCO3
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Normally HCO3/H2CO3 or HCO3/CO2 (normally 20:1)

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Normally

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 Bicarbonate Bicarbonate Bicarbonate Bicarbonate Bicarbonate Bicarbonate Bicarbonate Carbonic Acid Bicarbonate Bicarbonate Bicarbonate Bicarbonate Bicarbonate Bicarbonate Bicarbonate Bicarbonate Bicarbonate Bicarbonate Bicarbonate Bicarbonate

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Haendresson Hesselbach Equation

pH = 6.1 + log = 7.4 P-CO2

[HCO3-]

[HCO3-] log = 1.3 P-CO2

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Normal values of bicarbonate

(arterial) pH = 7.4 PCO2 = 40 mm Hg HCO3- = 24 meq/L

ACIDOSIS / ALKALOSIS

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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

ACIDOSIS / ALKALOSIS

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May be caused by: An increase in H2CO3 A decrease in HCO3Both lead to a decrease in the ratio of
20:1

ACIDOSIS

H2CO3

HCO3

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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) Uncontrolled DM 3) Kidney Insufficiencies 4) Strenuous Exercise 5) Severe Diarrhea

METABOLIC ACIDOSIS

Prolonged deep (from duodenum) vomiting

can result in the same situation

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Can be the result of: 1) Ingestion of Alkaline Substances 2) Vomiting ( loss of HCl )

METABOLIC ALKALOSIS

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 Decreased CO2 removal

RESPIRATORY ACIDOSIS

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 4) Collapse of lung
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RESPIRATORY ALKALOSIS

Can be the result of: 1) Anxiety, emotional

disturbances 2) Respiratory center lesions 3) Fever 5) Assisted respiration 6) High altitude (low PO2)
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ACIDOSIS
decreased removal of CO2 from lungs failure of kidneys to excrete acids metabolic acid production of keto acids absorption of metabolic acids from GI tract prolonged diarrhea

accumulation of CO2 in blood

accumulation of acid in blood

excessive loss of NaHCO3 from blood

respiratory acidosis

increase in plasma H+ concentration

metabolic acidosis

deep vomiting from GI tract kidney disease (uremia)

depression of nervous system

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ALKALOSIS
anxiety overdose of certain drugs high altitudes prolonged vomiting ingestion of excessive alkaline drugs excess aldosterone

hyperventilation loss of CO2 and H2CO2 from blood

loss of acid

accumulation of base

respiratory alkalosis
decrease in plasma H+ concentration

metabolic alkalosis

overexcitability of nervous system

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Anion Gap
Definition
- It is the difference between the sum of the concentrations of the major plasma cations and the major anions. - The anion gap = [Na+ + K+] [Cl- + HCO3-].

Normal value

16 mEq/L.

Importance

Sometimes K+ is omitted from calculation and the anion gap = 12 mEq/L. - In metabolic acidosis, serum HCO3- decreases. - Thus, concentration of another anion must increase to maintain electroneutrality. - This anion can be chloride or other unmeasured anions.

The anion gap is increased

-

If concentration of other unmeasured anions is increased as in metabolic acidosis due to renal failure, lactic acidosis and diabetic ketoacidosis.

The anion gap is normal

- If concentration of chloride increased (hyperchloremic acidosis)
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The anion gap will increase if

The major un-measured anions are

The plasma anion gap is used
albumin, phosphate, sulfate and other organic acids.

unmeasured anions are increased.

clinically in diagnosing different causes of metabolic acidosis.

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