Principles of Acid-Base Physiology

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Principles of Acid-Base Physiology

• Mazen Kherallah, MD, FCCP
• Internal Medicine, Infectious Disease and
  Critical Care Medicine

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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-

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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.

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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

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Normal Concentration of Cations and Anions in
Plasma
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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)

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Compartmental H
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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.

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Intracellular Buffers

• Binding to Proteins
• Buffered by inorganic phosphate

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Intracellular BuffersInorganic Phosphate
HPO42- divalent inorganic phosphate ion
H2PO4- monovalent dihydrogen inorganic
phosphate ion
HPO42- pH pK
log ---------- H2PO4-
pK for inorganic phosphate is close to 6.8
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pH of Different Compartments
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Physiology of Phosphate Buffers
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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

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No Change in Net ChargeNeutrals to Neutrals

• Glucose ? Glycogen CO2 H2O
• TG ? CO2 H2O
• Alanine ? Urea Glucose

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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-

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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

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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

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Reactions that Remove H

• Lactate- H ? Glucose
• Citrate 3- 3H ? CO2 H2O
• Glutamine ? Glucose NH4 CO2 H2O HCO3-

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Dietary Acid-Base Impact
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Sulfur-containing Amino AcidsCysteine/Cystine
and Methionine

• Sulfur-containing amino acids can be oxidized to
  yield the terminal anion SO42- plus neutral
  end-product (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

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Cationic Amino AcidsLysine, Arginine, and
Histidine

• Are metabolized to neutral end-products plus H
• These H requires the excretion of NH4 to
  prevent accumulation of protons

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Rate of Production of H
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Anions are metabolized to neutral products almost
as fast as they are produced Starvation
Ketoacidosis L-lactic acid usual rate Anions
that are produced slowly and excreted with H and
NH4 H2SO4 from proteins
L-lactic acid due to low supply of O2
Exercise Shock
DKA L-lactic acid liver problem Organic acids
from gut butyric acid, acetic, and
propionic Anions from toxins NH4 excretion problem
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Range of H in Plasma in Clinical Conditions
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Fuels ? H
(70 mmol per day)
Lungs
HCO3-
CO2
Glutamine
NH4
Kidneys
(Kidney must generate 70 mmol of HCO3 per day)
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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

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Generation of New HCO3 in the Kidney
HCO3- (to blood)
HCO3- (to blood)
CO2 H2O
H (Secreted)
Glutamine
Filtered HPO42-
NH4 (to urine)
H2PO4- (to urine)
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Concept

• Buffers work physiologically to keep added H
  from binding to proteins instead H are forced
  to react with HCO3-

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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.

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Buffers for an Acid Load
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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

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Bicarbonate Buffer System (BBS)
H HCO3- ? H2CO3 ? H2O CO2
HCO3- pH pK log
---------- H2CO3
H 24 X PCO2/HCO3-
Each mmol of HCO3- remove 1 mmol of H
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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

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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

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Teamwork in BBS buffer
ECF H HCO3- ? H2O CO2 ? lungs
ICF H HCO3- ? H2O CO2
(falls)
B?
HB
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Bicarbonate Buffer SystemImportance of CO2
Removal