1. Dr. Vishal Golay

2. Basic terminology
• pH – signifies free hydrogen ion concentration. pH is inversely
related to H+ ion concentration.
• Acid – a substance that can donate H+ ion, i.e. lowers pH.
• Base – a substance that can accept H+ ion, i.e. raises pH.
• Anion – an ion with negative charge.
• Cation – an ion with positive charge.
• Acidemia – blood pH< 7.35 with increased H+ concentration.
• Alkalemia – blood pH>7.45 with decreased H+ concentration.
• Acidosis – Abnormal process or disease which reduces pH due to
increase in acid or decrease in alkali.
• Alkalosis – Abnormal process or disease which increases pH due to
decrease in acid or increase in alkali.

3. Daily production ~ 1 mEq of H+/kg/day
 Sulfuric acid ( from sulphur containing AA)
 Organic acids (from intermediary metabolism)
 Phosphoric acid ( hydrolysis of PO4 containing proteins)
 Hydrochloric acid (from metabolism of cationic AA-
Lysine, Arginine, Histidine)

4. pH in humans is tightly regulated between 7.35-
7.45.
Chemical
Buffers
Respiratory
regulatory
responses
Renal regulatory
responses

5.  Buffers are chemical systems which either release or
accept H+ and minimize change in pH induced by an
acid or base load.
 First line of defense blunting the changes in [H+]
A buffer pair consists of:
A base (H+ acceptor) & an acid (H+ donor)

6. Buffers continued……
Extracellular buffers: Intracellular buffers:
•Hemoglobin
Examples:
•Proteins
• HCO3¯/H2CO3
HPO42- + (H+•Organophosphate
)↔H2 PO4-
• HPO4²¯/H2PO4¯ compounds
• Protein buffersCO2 ↔H2 CO3 ↔H+ + HCO3-
H2 O + •Bone apatite

7.  2nd line of defense
 10-12 mol/day CO2 is accumulated and is
transported to the lungs as Hb-generated HCO3 and
Hb-bound carbamino compounds where it is freely
excreted.
H2 O + CO2 ↔H2 CO3 ↔H+ + HCO3-
 Accumulation/loss of CO2 changes pH within
minutes

8.  Balance affected by neurorespiratory control of
ventilation.
 During Acidosis, chemoreceptors sense ↓pH and
trigger ventilation decreasing pCO2.
 Response to alkalosis is biphasic. Initial
hyperventilation to remove excess pCO2
followed by suppression to increase pCO2 to
return pH to normal

9.  Kidneys are the ultimate defense against the
addition of non-volatile acid/alkali.
HA + NaHCO3↔H2 O + CO2 + NaA
Addition of Acid causes loss of HCO3¯
 Kidneys play a role in the maintenance of this HCO3¯
by:
 Conservation of filtered HCO3 ¯
 Regeneration of HCO3 ¯

10.  Kidneys balance nonvolatile acid generation
during metabolism by excreting acid.
 Each mEq of NAE corresponds to 1 mEq of
HCO3¯ returned to ECF.
 NAE has three components:
1. NH4⁺ .
2. Titrable acids (acid excreted that has titrated urinary
buffers)
3. Bicarbonate.
NAE= NH4⁺ + TA-
HCO3¯

12. Generally a metabolic acidosis develops due to:
1. Failure of NAE to match with the endogenous acid
production.
2. Failure to recapture filtered HCO3-
There is an absence of renal compensation in ESRD
making interpretation simpler.

13. In addition to CKD per se:
 DKA  GI alkali loss
 Alcoholic ketoacidosis  Hemofiltration with NaCl
 Lactic acidosis replacement
 Toxin ingestion  Ammonium chloride
 Catabolic state ingestion
 High protein intake
 Large salt and water
intake between dialysis

14.  Vomiting
 Nasogastric drainage
 Exogenous alkali supplementation (NaHCO3,
KHCO3, CaCO3, Lactate, Acetate, Citrate,
Glutamate, Propionate)
 Alumimium hydroxide + Na Polysterine sulfonate
coadministration

15.  Respiratory acidosis-hypoventilation
 Respiratory alkalosis-hyperventilation
It is important to remember that respiratory acid-
base disorders are dangerous in ESRD
as there is no renal compensation.

16. Laboratory evaluation in patients with ESRD
should include not only HCO3 measurement but
also pH and CO2.
Example:
Even with a HCO3¯ in the normal range, the
patient maybe having a dangerously high pH and
low PCO2 due to respiratory alkalosis.

17. Metabolic acidosis:
 Initially hyperchloremic but becomes high AG as
ESRD sets in.
 Associated with:
 Insulin resistance
 GH/IGF-1 axis suppression
 Mineral bone disease
 Protein degradation and muscle wasting
 Increase risk of mortality
 ITT studies show delay in progression of CKD with Rx

18. Metabolic alkalosis:
 Nausea, lethargy and headache
 Soft tissue calcification
 Cardiac arrhythmia
 Sudden death
 Reflection of a low protein intake in dialysis patients.
 Poses risk for dangerous alkalosis with minimal
hyperventilation.

19. Respiratory alkalosis:
 Dizziness, confusion, seizures (if acute).
 Cardiovascular compromise (specially if ventilated).
 Reflects underlying diseases which have a poor outcome.
Respiratory acidosis:
 Anxiety, dyspnea, confusion, hallucinations, coma.
 Sleep disturbances, loss of memory, daytime
sleepiness, tremor, myoclonus, asterixis.
Poor compensation may cause dramatic changes in Ph

20.  Correction is by adding HCO3- instead of the removal
of H+.
 This regulation is un-physiologic and determined by
the physical principles of diffusion and convection.
Gain of HCO3- in dialysis is determined by the
transmembrane concentration gradient
Dialysis prescription (fixed) Endogenous acid production (variable)

22. 1950’s-1960’s:
 HCO3¯ was the alkali source.
 Initially 26mM/L→ later 35mM/L
 pH was adjusted to 7.4 to prevent CaCO3 ppt. by
aeration with CO2/O2 gas mixture.
 Central solution preparation was not possible.

23. 1960’s -1980’s:
 Acetate became the chief alkali used.
 Aim was to create a positive balance of acetate (3-4mM/L)
which is later metabolized to HCO3¯.
 A value of 37mEq/L was set by trial and error.
 It was inefficient (avg. predialysis HCO3¯ was <18mM/L)
and needed large acetate levels which accumulated as
dialysis became more efficient
 Toxicity: hypotension, CO2 loss (decreased ventilatory
drive and hypoxemia).

24.  Proportioning systems enabled use of HCO3¯.
 Acetic acid in the “acid concentrate” reacted with
HCO3¯ to generate acetate which prevented a rapid
rise of pH.
 Thus the final dialysis solution composition
became:
 HCO3¯ =30-40mM/L
 Acetate=2-4mM/L
 pH=7.1-7.3
 This raised the avg. predialysis HCO3¯ by 3-4mM/L

25.  Sorbent cartridge hemodialysis.
 Hemofiltration.
 Acetate-free biofiltration.

26. Dialysiance of
HCO3¯
Transmemb. HCO3¯ gradient over time

27.  Postdialysis HCO3¯ :
 Determined by the dialysis prescription.
 Predialysis HCO3¯ :
 Endogenous acid production between Rx (diet, catabolic
state)-This may cause variations as large as 6mEq/L
 Rate of fluid retention-”dilution acidosis” . 1 L ot fluid
retained can affect preHD HCO3¯ by >1mEq/L.
The avg. preHD HCO3¯ values in stable patients on
3/wk HD is 19-25mEq/L.

28.  Target for a preHD HCO3¯ of >22mEq/L (following
the KDIGO-CKD 2012 guidelines).
 Some reasonable targets are:
 Intradialytic gain of 6-10mM/L of HCO3¯
 Target post HD HCO3¯ of 30-34mM/L (risky in some) using
a higher bath HCO3 of ~36-40mM/L
 A more reasonable target would be a post-HD HCO
Always look for causes if target not achieved 3¯ of
approx. 27mM/L once acidosis is controlled.
(eg. nutrition, fluid intake, RRF with loss of HCO3¯, loss
 Only definite way is to measure pre and post HD HCO3¯
in stool etc.)
levels.

29. Daily hemodialysis (nocturnal HD or short daily HD):
 These modalities quickly normalizes HCO3¯.
 Pre and post HD variations can be <1mM/L.
 Thus, a lower bath HCO3¯ of 28-32mM/ should be
used.

30. Critical care settings:
 Always evaluate the acid-base status before HD.
 They are high risk for alkalosis.
 If the pre HD HCO3¯ is >28mM/L or there is respiratory
alkalosis, use a bath with lower HCO3 (eg. 20-28mM)
 Respiratory alkalosis=normalize pH and not HCO3¯.
 Severe preHD metabolic acidosis (HCO3¯ <10mM/L): excess
correction can paradoxically cause CSF acidification and
lactic acidosis).

31. Kussmaul’s respiration (deep and rapid)
Cheyne-Stokes respiration
•Brain injury
•CO poisoning
•Metabolic encephalopathy
Biot’s breathing
•Medullary injury
•Chronic opioid use
Apneustic respiration
•Damage to upper pons
Ataxic respiration
•Damage to the medulla oblongata

32. THANK YOU