Download Principles of Acid Base Balance

Principles of Acid-Base
Physiology
Mazen Kherallah, MD, FCCP
Internal Medicine, Infectious Disease
and Critical Care Medicine
Note
• Acids are compound that are capable of
donating a H+
• Bases are compound that are capable of
accepting a H+
• When an acid HA dissociates, it yields a H+
and its conjugate base (anion, A-)
• HA  H+ + A-
Valence
• The number of charges a compound or ion
bears in solution, expressed in mEq/L.
• The term mEq reflects the number of
charges or valences.
• Therefore multiply mmol by the valence to
obtain mEq.
• Valence is especially important for albumin,
which has a large valence on each molecule.
Characteristics of
+
H
• The free H+ is tiny and must be kept so for
survival
• A very large accumulation of H+ may kill by
binding to proteins in cells and changing
their charge, shape, and possibly their
function
Normal Concentration of Cations
and Anions in Plasma
Cations
(mEq/L)
Anions
(mEq/L)
Na+
140
CL-
103
K+
4
HCO3-
25
Ca2+
5
Proteins
16
Mg2+
2
Organic
4
H+
0.00004 (40
nmol/L)
Other inorganics 3
Number of H+ in the body
• ECF: 15 L X 40 nmol/L = 600 nmol
• ICF 30 L X 80 nmol/L = 2400 nmol
• Total free H+ in the body is close to 3000
nmol/L
• Close to 70.000.000 nmol of H+ is formed and
consumed daily
• Affinity of H+ for chemical groups on organic
and inorganic compounds determine whether
H+ will be bound or remain free (gastric)
Compartmental
+
[H ]
ECF
40 nmol/L
ICF
80-100 nmol/L
Urine
10,000 nmol/L
Gastric fluid
70 mmol/L
Gastric
+
[H ]
• Very high concentration is needed to initiate digestion
• The anion secreted by the stomach along with [H+] is
Cl• Cl- will not bind H+ because HCl dissociates completely
in aqueous solution and there are no major buffers in the
gastric fluid
• H+ bind avidly when they come in contact with ingested
proteins.
• Binding of H+ makes the protein much more positively
charged and alters its shape so that pepsin can gain
access to the sites it will hydrolyze in that protein.
Intracellular Buffers
• Binding to Proteins
• Buffered by inorganic phosphate
Intracellular Buffers
Inorganic Phosphate
HPO42-: divalent inorganic phosphate ion
H2PO4-: monovalent dihydrogen inorganic phosphate ion
HPO42pH= pK + log ---------H2PO4pK for inorganic phosphate is close to 6.8
pH of Different Compartments
PH
Compartment
Ratio of
HPO42-/H2PO4-
7.4
ECF
4/1 (0.62)
7.1
ICF
2/1 (0.3)
5.8
Urine
1/10 (-1)
Physiology of Phosphate Buffers
Compartment
ECF
Total
% as of
Equation
Inorganic H2PO4Phosphate
1 mmol/L 20%
H+ +HPO42-H2PO4-
ICF
4-5 mmol/L 33%
H+ +HPO42-H2PO4-
Urine
30 mmol/L 90%
H+ +HPO42-H2PO4-
Definition of Metabolic Process
• A metabolic process starts with either
dietary or stored fuels and ends with ATP or
an energy store (glycogen, triglyceride)
• If part of the pathway generates H+ and is
intimately linked to another part that
removes H+, both parts can be ignored from
an acid-base perspective
No Change in Net Charge
Neutrals to Neutrals
• Glucose  Glycogen + CO2 + H2O
• TG  CO2 + H2O
• Alanine  Urea + Glucose
No Net Production or Removal of H+
At the Cellular Level
• H+ is formed when ATP is hydrolyzed to
perform biologic work: reabsorb Na+
– ATP4-  ADP3- + Pi2- + H+
• As soon as ATP is regenerated in the
mitochondria of that cell, H+ are removed
– ADP3- + Pi2- + H+  ATP4-
No Net Production or Removal of H+
Multiple Organ Process
• Adipocyte:
– TG  3 Palmitate- + 3 H+ + Glycerol
• Liver:
– 3 Palmitate- + 3 H+ + 18 O2  12 ketoacid
anions + 12 H+
• Brain:
– 12 ketoacid anions + 12 H+  CO2 + H2O +
ATP
Reactions that Yield H+
• Glucose  Lactate- + H+
• Fatty acid  4 Ketoacid anions + 4 H+
• Cysteine  Urea + CO2 + H2O + SO42+ 2H+
• Lysine+  Urea + CO2 + H2O + H+
Reactions that Remove H+
• Lactate- + H+  Glucose
• Citrate 3- + 3H+  CO2 + H2O
• Glutamine  Glucose + NH4+ + CO2
+ H2O + HCO3-
Dietary Acid-Base Impact
Nutrient
Product
H+
(mEq/day)
H+
70
H+
140
HPO42-+H+
30
Anionic amino acids:
Glutamate, aspartate
Organic anions (citrate3-)
HCO3-
-110
HCO3-
-60
Posphate excretion
H2PO4-
-30
Reactions generating H+
Sulfur-containing amino acids:
Cysteine/cystine, methionine
Cationic amino acids:
Lysine, arginine, histidine
Organic phosphates
Reactions removing H+
Net total H+ load to be excreted as
NH4+
40
Sulfur-containing Amino Acids
Cysteine/Cystine and Methionine
• Sulfur-containing amino acids can be oxidized to
yield the terminal anion SO42- plus neutral endproduct (glucose, urea, CO2 and and H2O)
• Because the affinity SO42- of for H+ is so low
(SO42- has a very low pK), SO42- cannot help in
removing H+ by urinary excretion
• Hence other ways are needed to remove these H+
( renal excretion of NH4+)
• For each SO42- mEq of that accumulate or
excreted without NH4+, H+ accumulate
Cationic Amino Acids
Lysine, Arginine, and Histidine
• Are metabolized to neutral end-products
plus H+
• These H+ requires the excretion of NH4+ to
prevent accumulation of protons
Rate of Production of
Event
Rate
( mmol/min)
+
H
Comment
Production of H+
Lactic acid
Ketoacids
72
7.2
1
Complete anoxia
10% hypoxia
Lack of insulin
Toxic alcohols
<1
Poisening metabolites
0-2
Lag period
Lactic acid
4-8
Oxidation and glucogenesis
Ketoacids
0.8
Oxidized in brain and kidney
Removal of H+
Excretion of NH+
Metabolism
Reactions that produce H+
Is H+ accumilating
Yes
No
Anions are metabolized to neutral
products almost as fast as they are
produced:
Starvation Ketoacidosis
YEs
No
L-lactic acid: usual rate
Anions that are produced slowly
L-lactic acid
and excreted with H+ and NH4+
due to low
DKA
H2SO4 from proteins
supply of O2:
L-lactic acid: liver problem
Exercise
Organic acids from gut: butyric acid, acetic, and propionic
Shock
Anions from toxins
NH4 excretion
problem
Was H+ produced
at a much faster
rate than it was
removed
Range of [H+] in Plasma in
Clinical Conditions
Condition
[H+] nmol/L
pH
Importance
Acidemia
>100
<7.00
Can be lethal
Acidemia
50-80
7.1-7.30
Normal
402
7.400.002
Clinically
important
Normal
Alkalemia
20-36
7.44-7.69
Alkalemia
<20
>7.70
Clinically
important
Can be lethal
Fuels  H+
(70 mmol per day)
Lungs
CO2
HCO3Glutamine
NH4+
Kidneys
(Kidney must generate 70 mmol of HCO3 per day)
Generation of New HCO3• Each day 70 mmol is derived from the normal
oxidative metabolism of dietary constituent
and is buffered mainly by bicarbonate buffer
system (BBS)
• To achieve acid-base balance, the kidney must
generate 70 mmol of new HCO3- to replace
the HCO3- consumed by the buffering process
• Should this process fails, the patient will
become acidemic
Generation of New HCO3 in the
Kidney
HCO3- (to blood)
HCO3- (to blood)
CO2 + H2O
H+ (Secreted)
Glutamine
Filtered
HPO42NH4+ (to urine)
H2PO4- (to urine)
Concept
• Buffers work physiologically to keep
added H+ from binding to proteins;
instead H+ are forced to react with
HCO3-
Chemistry of Buffers
• Each buffer has its unique dissociation
constant (pK), which determine the range of
[H+] at which the buffer is effective
• HAA- + H+
• pH= pK+ log HA/A• A buffer is most effective at a [H+] or pH
the is equal to its pK
• Strong acids have a lower pK, and weak
acids have higher pK.
Buffers for an Acid Load
Buffers (mmol)
Location
HCO3-
Proteins
Phosphate Other
ECF
375
<10
<15
0
ICF (muscle)
330
400
<50
CrP
Protein Buffer System
• The major non-BBS buffer is protein in the
ICF (imidazole group in histidine)
• When H+ binds to proteins, the charge, shape,
and possibly function of proteins may change
• Total content of histidines is close to 2400
mmol in 70-kg individual
• PH of ICF is close to pK of histidine
• Only 1200 mmol of histidine are potential H+
acceptors
Bicarbonate Buffer System
(BBS)
H+ + HCO3-  H2CO3  H2O + CO2
HCO3pH= pK + log ---------H2CO3
[H+] = 24 X PCO2/HCO3Each mmol of HCO3- remove 1 mmol of H+
Bicarbonate Buffer System
Quantities
• Total content of HCO3- in the ECF is:
– 25 mmol/L X 15 = 375 mmol
• Total content of HCO3- in the ICF is:
– 13 mmol/L X 30 = 360 mmol
Bicarbonate Buffer System
Physiology
• A function of the BBS is to prevent H+ from
binding to proteins in the ICF
• The BBS is used first to remove a H+ load,
providing that hyperventilation occurs
• The key to the operation of the BBS is the
control of the PCO2
Teamwork in BBS buffer
ECF:
ICF:
H+ + HCO3-  H2O + CO2  lungs
H+ + HCO3-  H2O + CO2
B
HB+
(falls)
Bicarbonate Buffer System
Importance of CO2 Removal
Condition
[H+]
(nmol/L)
PH
PCO2
HCO3(mm Hg) (mmol/L)
Closed system
(PCO2 rises)
871
6.06
455
12.5
No change in
PCO2
77
7.11
40
12.5
Lower PCO2
52
7.29
27
12.5