Physiology 4.

November 25, 2011

Acid-Base Regulation

Dr. Milagros Rabe

I.
II.
III.
IV.
V.
VI.
VII.
VIII.
IX.

OUTLINE
Definitions
Types and Sources of Acid
Acid Base Balance
Regulation of Acid Base Balance
Primary Acid-Base Disturbances
Interpreting ABGs
Compensatory Mechanism
Anion Gap
Simple vs. Mixed Acid-Base Balance

II. TYPES AND SOURCES OF ACIDS

Volatile Acids:

Objectives:

Review: Acids and Bases; Chemistry

Review: Sources of acids in the body
Give the significance of acid-base balance regulation
Give the significance of buffers in the body
Enumerate the buffer systems
Explain the different compensatory responses to regulate acid-base balance
o
Respiratory
o
Renal
Give the expected compensatory responses
Predict the expected acid base problems and compensatory responses given
clinical problems

I. DEFINITIONS: CHEMISTRY
+

Non-Volatile Acids

Acid: proton donor, eg. HCl H + Cl

Base: proton acceptor, eg. HCO3 NH3 + CH3COO
Strong acid vs. weak acid = complete vs slight dissociation in
aqueous solution
o Strong acids when put in an aqueous solution dissociate
completely
o Strong acid weak conjugate base
+
Eg: HCl H + Cl
Conjugate base = usually anion
o Strong base weak conjugate acid
+
Eg: NaOH Na + OH
Conjugate acid = anion or cation
-5
10 mol/L HCl = weak concentration of a strong acid
5 mol/L CH3COOH (acetic acid) = strong concentration of a weak
acid
I. DEFINITIONS
pH

-log

Volatile acid :because it has the potential to generate H+ after

hydration with H2O (Berne and Levy)
H2CO3; lung excretion
Decarboxylation reactions in TCA cycle
Basal conditions: 300L (13mol) CO2 / day
+
CO2
+
H2O

H2CO3

H
+
HCO3
+
H + Hb HHb
+
o For every H2CO3 that dissociates, H is buffered by BC or plasma
HCO3 is produced
o At any given pH, reduced blood (deoxyHb) has more HCO 3 than
oxygenated blood
When you break down glucose to produce ATP CO2 and H2O is
produced
o CO2 is a volatile acid, it is carried as bicarbonate, dissolved or
attached to hemoglobin

[H ]

= log (1/[H ])
Henderson-Hasselbach Equation
o pH
=
pK1
+
log
[HCO3 ]/S
x
pCO2
= 6.1 + log [HCO3 ] /0.03 x pCO2
+
o pK is the negative logarithm of [H ] at which half of the acid
molecules are not dissociated and half are dissociated
o S is the solubility constant of CO2 in plasma at 38C
+
o Expresses H concentration in pH units rather than in actual
concentration
o An increase in bicarbonate concentration causes the pH to rise
acid-base balance shift toward alkalosis
o Increase in PCO2 causes the pH to decrease acid-base balance
shift toward acidosis
o Bicarbonate concentration is regulated mainly by the kidneys,
whereas PCO2 in ECF is controlled by the rate of respiration

Group # 7| Biag H, Bibay, Bias, Bitoon, Blancaflor, Blanco, Bobadilla, Bollos

Source: mainly from metabolism of CHON- 80miliequivalent

(Guyton)
Phosphoric and sulfuric acids (diet = phosphoprotein and
methionine)
+
o 50-70 mEq H per day
Intermediary metabolism (lactic and ketoacids)
They are neutralized by buffers in the blood and tissues
o Neutralized by bicarbonate produced by the kidneys
They cannot be converted to CO2 and thus, are not released by the
respiratory tract
Renal excretion is the only mode of removing these acids.(Guyton)
IV. ACID BASE BALANCE
+

[H ] = 40 nmol/L
Normal pH = 7.35 7.45
Defenses:
1. Chemical buffers in blood (phosphate, bicarbonate,
hemoglobin)
2. Changes in alveolar ventilation- removal of CO2( Guyton)
+
3. Regulation of renal H excretion and HCO3 reabsorption
Responses to acid-base disturbances
Immediate
o Blood buffers
Short term
o Respiratory compensation
Long term
o Renal compensation

Page 1 of 4

Table 1. Blood Buffers

Non bicarbonate Bicarbonate

Buffer type

Buffering capacity (%)

Plasma

35

Erythrocyte

18

Hemoglobin and oxyhemoglobin

35

Plasma proteins

Organic phosphate

Inorganic phosphate

* Note that Bicarbonate plays an important role in extracellular buffering while

Phosphates have minimal role
**In RBC(IC), Hb is the most important buffer (Guyton) ***
**bicarbonate buffer system is the most powerful extracellular buffer in the
body. (Guyton)
Tissue Buffers

Buffer Power of system is determined by the amount and relative

concentrations of the buffer components
+
Major buffer capacity of body are found in H acceptors in tissues
o Mainly muscle proteins as this is most abundant tissue in body
o Muscle cells have 12 mEq/L HCO3
o Bone carbonate is 50 times more the amount of HCO3
Phosphate Buffer System role in buffering renal tubular-fluid and
intracellular fluids
Tissues neutralize 5 times as much acid as blood buffers
Hemoglobin is the most important buffer in RBC
Most of body buffers located in ICF, hemoglobin is in ICF
Unoxygenated Hb can bind with H and act as buffer(Guyton)
pH of ECF can be controlled by the relative rate of removal and
addition of bicarbonate and rate of removal of carbon dioxide

o Decreasing rate of respiration lungs elevate PCO 2 increases

+
CO2 increases H concentration in ECF (above normal)
respiratory system is stimulated alveolar ventilation increases
+
PCO2 in ECF decreases reduces H concentration back to
normal
+
Increase [H ] or decreased pH stimulates central chemoreceptors (in
the ventral surface of the medulla) and peripheral chemoreceptors
(carotid and aortic bodies) to increase pulmonary ventilation
Respiratory response to metabolic acid-base disturbances may be
initiated within minutes but could require several hours to complete
Renal Regulation
Although the kidneys are relatively slow to respond compared with the
other defenses, over a period of hours to several days, they are by far
the most powerful of the acid-base regulatory systems. (Guyton)
Elimination of non-volatile acids kidneys
o Acid phosphate (H2PO4) most abundant weak acid waste
product of metabolism
o Others: lactic acids and ketoacids
Diet type influences non-volatile acid production that the kidneys
eliminate
o High protein diet produces more sulfuric acid
o Vegetarian diets are associated with large intake of lactate and
acetate
o Half of metabolically produced acids are neutralized by base in
the diet
o Others buffered by anion systems of the body and by HCO3
o Various urinary buffers are termed titratable acids (Berne and
Levy)
+

Excretion of H by the Kidneys

Arterial Blood Gases (Normal Values)

**note: must know! So memorize!!
pH = 7.4 0.03
+
[H ] = 40 3 nmol/L
pCO2 = 40 5 mmHg
[HCO3 ] = 24 4 mmol/L
pH = 6.1 + log ([HCO3 ] / 0.03 * pCO2)
+
[H ] = 24 * (pCO2 / [HCO3])
V. REGULATION OF ACID BASE BALANCE
Respiratory regulation
CO2 transport
o 90% as HCO3
o 5% as carbaminohemoglobin
o 5% as dissolved CO2
For every 10 mmHg rise in pCO2 above 40 mmHg, [HCO3 ] increases
by 1 mEq/L
pCO2 is inversely related to pulmonary ventilation
o pCO2, respiration rate
o The main stimulus for respiration is CO2
Short term regulation
Regulates volatile acid elimination
+
Respiratory system acts as a negative feedback controller of H
concentration
Group # 7| Biag H, Bibay, Bias, Bitoon, Blancaflor, Blanco, Bobadilla, Bollos

CO2 is soluble across the plasma membrane

For H to be reabsorbed, it must react with HCO3 forming H2CO3
Thus, the kidneys regulate extracellular fluid H+ concentration through
three fundamental mechanisms: (1) secretion of H+, (2) reabsorption
of filtered HCO3 and (3) production of new HCO3 (Guyton).
+

Regulation of H Secretion (Berne and Levy)

+

primary factor that regulates H secretion by the nephron is

a change in systemic acid-base balance
HCO3 Reabsorption along the Nephron

Page 2 of 4

proximal tubule reabsorbs the largest portion of the filtered

load of HCO3
+

H is secreted into tubular fluid, whereas HCO3 exits the cell

across the basolateral membrane and returns to the
peritubular blood

Via :
+
o 1Na with 3HCO3 cotransporter
+
+
o Na -independent and/or Na -dependent Cl -HCO3
antiporters
o carbonic anhydrase in brush border of the PCT-->
+
(In the lumen)H2CO3---> HCO3 + H
Production of New HCO3

Generation of new HCO3 is achieved by the excretion of

titratable acid and by the synthesis and excretion of
+
NH4 .
+

NH4 is produced in the kidneys via the metabolism of

glutamine
V. PRIMARY ACID BASE DISTURBANCES
Metabolic acidosis
o Primary decrease in plasma [HCO3 ] due to non-carbonic acid
accumulation or [HCO3 ] loss in ECF
Ex. Renal Tubular Acidosis,Diarrhea, Vomiting of Intestinal
Content, Diabetes Mellitus, Ingestion of Acids, Chronic Renal
Failure. (Guyton)
Metabolic alkalosis
+
o Primary increase in plasma [HCO3 ] due to H (non-carbonic acid)
loss or [HCO3 ]gain in the ECF
Ex. Administration of Diuretics (Except the Carbonic Anhydrase
Inhibitors), Excess Aldosterone, Vomiting of Gastric Contents,
Ingestion of Alkaline Drugs.( Guyton)
o Due to acid loss in the stomach/kidney
Vomiting, nasogastric drainage
Loss of Cl will decrease availability for renal reabsorption
+
with Na
+
o Note: excess aldosterone will lead to K depletion with alkalosis
+
+
+
Aldosterone causes retention of Na lose K and H
metabolic alkalosis
Respiratory acidosis
o Decreased ventilation retaining CO2
o Primary increase in pCO2 (alveolar hypoventilation)
o Eg: sleeping pill overdose
will depress opioid receptors in the command center for
respiration in the medulla
leading to retention of CO2
Respiratory alkalosis
o Manifest as hyperventilation causing decrease in pCO2

VI. INTERPRETING ABGs

Look at the pH
o Is the primary acidosis (low) or alkalosis (high)?
Check the CO2 (respiratory indicator)
o Is it less than 35 (alkalosis) or more than 45 (acidosis)?
Check the HCO3 (metabolic indicator)
o Is it less than 22 (acidosis) or more than 26 (alkalosis)?
Which is primary disorder (respiratory or metabolic)?
o If the pH is low (acidosis), then look to see if CO 2 or HCO3 is
acidosis (whichever is acidosis will be primary).
o If the pH is high (alkalosis), then look to see if CO2 or HCO3 is
alkalosis

Group # 7| Biag H, Bibay, Bias, Bitoon, Blancaflor, Blanco, Bobadilla, Bollos

VII. COMPENSATORY MECHANISM

If respiratory system is main problem renal compensation
o Kidneys excrete more H and reabsorb more HCO3 in respiratory
acidosis, if pH is N but pCO2 is increased then the problem is not
acute and kidneys had time to compensate
o In respiratory alkalosis kidneys compensate by excreting more
HCO3
If main problem is loss or gain of non-volatile acid -> problem is
metabolic, compensation is through respiratory system
o If low pH due to increase HCO3 loss or gain in non-volatile acid
by increasing ventilation to increase loss of CO2
o If high pH due to primary acid loss, then the pulmonary
ventilation is decreased to retain CO2
Primary and Secondary Changes

When the primary disturbance is an alteration in blood PCO2, it is called a

respiratory disorder. During respiratory acidosis, rise of PCO2 increases total
carbon dioxide and as a compensatory response, HCO3- increases. Whereas
decreasing PCO2, in the case of respiratory alkalosis, HCO3- concentration is
reduced. When an acid-base disorder results from a primary change in [HCO3-],
it is called a metabolic disorder. In metabolic acidosis, there is decreased
bicarbonate concentration resulting to the reduction of PCO 2. In metabolic
alkalosis, increased bicarbonate concentration causes increased PCO 2 as
compensation.

Page 3 of 4

Normal Compensatory Responses

**note: memorize! Important in knowing if compensation is adequate
MAIN PROBLEM
EXPECT
Dec pCO2 by 1-1.3 mmHg for
Metabolic acidosis
Dec [HCO3]
every 1 mmol/L dec [HCO3]
Inc pCO2 by 0.6-0.7 mmHg for
Metabolic alkalosis
Inc [HCO3]
every 1 mmol/L inc [HCO3]
Acute respiratory
Inc [HCO3] by 1 mmol/L for
Inc pCO2
acidosis
every 10 mmHg inc pCO2
Chronic respiratory
Inc [HCO3] by 3-3.5 mmol/L for
Inc pCO2
acidosis
every 10 mmHg inc pCO2
Acute respiratory
Dec [HCO3] by 2 mmol/L for
Dec pCO2
alkalosis
every 10 mmHg dec pCO2
Chronic respiratory
Dec [HCO3] by 4-5 mmol/L for
Dec pCO2
alkalosis
every 10 mmHg dec pCO2
If predicted compensatory value is not the same it means there is
more than one cause of acid base problems
o Mixed acid base problem or compensation is not adequate

VIII. ANION GAP

Anion gap is the difference between positively charged (cations) and
negatively charged (anions) ions in blood
+
+
Anion Gap = ([Na ] + [K ]) ([Cl ] + [HCO3 ]
+
+
o But K is mainly intracellular, so mainly [Na ]
o Normal = 12 2 mmol/L (8-15mmol/L in some books)
2+
2+
o Normal AG due to presence of unmeasured cations (Ca , Mg ,
+
K ) and unmeasured anions (plasma proteins, phosphate,
sulphate)
Gap increases if unmeasured cations fall or unmeasured
anions rise
Only important for determining the potential reasons causes
METABOLIC ACIDOSIS
o Certain conditions with metabolic acidosis have a normal anion
gap, some with high anion gap
o AG > 12 mmol/L (high) = ketoacidosis (DM, starvation, alcohol
intoxication), lactic acidosis, pisoning (salicylates, ethylene glycol,
ethanol, methanol), chronic renal failure
o Normal AG = loss of HCO3 from GI tract/kidney (diarrhea, renal
tubular acidosis, urinary obstruction, intake of NH4Cl, Addisons
disease, use of Carbonic Anhydrase inhibitors)
Causes of anion gap acidosis: (Remember mUD PILES)
Uremia
Diabetic Ketoacidosis
Paraldehyde, phenformin
Iron, isoniazid, inhalants
Lactic Acidosis
Ethylene

glycol (alcoholic ketoacidosis)

Salicylates, solvents, starvation

o Patient vomiting (primary H loss) and also has pneumonia (CO2

retention)
o Diabetic but has pneumonia
o Patient with renal failure but is vomiting
Check history, arterial blood gas values, use an acid base
normogram

Case 1
A 44-year old moderately dehydrated man was admitted with a two
day history of acute severe diarrhea.
+
+
Electrolyte results (in mmol/L): Na 134, K 2.9, Cl 113, HCO3 16,
Urea 12.3, Creatinine 0.30 mmol/L.
Arterial Blood Gases:
pH 7.31 = net acidemia
pCO2 33 mmHg = low
pO2 not given
HCO3 16 mmol/L = low (decline by 8, expect pco2 to go down by roughly 8)
K 2.1 mmol/L
What is the anion gap?
= [Na=134]+[K=2.9]-[Cl=113]+[HCO3= 16]
= 136.9-129
= 7.9 or 8 mmol/L normal (diarrhea is a condition that can show a
normal anion gap)
What is the patients acid base status?
Low HCO3 and low pCO2 levels are seen in METABOLIC
ACIDOSIS and RESPIRATORY ALKALOSIS
BUT history shows patient had diarrhea (loss of HCO3) and
moderate dehydration which will most likely cause
METABOLIC ACIDOSIS
What happened?
Diarrhea -> loss of HCO3, Na+ from still
Dehydration (low blood volume) -> decreased renal perfusion
-> retention of creatinine and urea (pre renal failure)
= kidneys unable to produce as much HCO3, pH cannot be
fully corrected in 2 days
Was compensatory response adequate?
The maximal amount of respiratory compensation takes 12- 24
hours to occur so sufficient time has elapsed
o The expected PCO2 should be 1.3 mm Hg/ 1 mmol
decline in HCO3
o Normal HCO3 = 24 +/- 4 mmHg
o PCO2 = 40+/- mmHg
Patient ABGs
o PCO2 = 33mmHg: HCO3 = 16mmol/L
o 24-26 = mmol
Expected decline in PCO2 = 40-8
= 32 mmHg
Compensation is ADEQUATE!

VIII. SIMPLE VS. MIXED ACID BASE PROBLEMS

Simple acid base problem = caused by one primary factor only
Mixed disturbances = due to more than one primary factor
o Can be found in:
Patients with emphysema (CO2 retention) and with
uncontrolled diabetes mellitus (ketoacidosis= more than
one source of an acid)
Group # 7| Biag H, Bibay, Bias, Bitoon, Blancaflor, Blanco, Bobadilla, Bollos

Page 4 of 4