Acid-base and related complications in hemodialysis in CKD

Dr. Vishal Golay

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.

Endogenous sources of acid

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)

pH in humans is tightly regulated between 7.35-7.45.

Renal regulatory responses

Respiratory regulatory responses

Chemical

Buffers

Buffers

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)

Buffers continued……

Extracellular buffers:

• HCO3¯/H2CO3

• HPO4²¯/H2PO4¯• Protein buffers

Intracellular buffers:•Hemoglobin•Proteins•Organophosphate compounds•Bone apatite

Examples:

HPO42- + (H+)↔H2 PO4

-

H2 O + CO2 ↔H2 CO3 ↔H+ + HCO3-

Respiratory regulation

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

Respiratory regulation contd…..

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

Renal Regulation

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 ¯

Net Acid Excretion(NAE)

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¯

What goes wrong in CKD?

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.

Metabolic acidosis in ESRDIn addition to CKD

per se: DKA Alcoholic

ketoacidosis Lactic acidosis Toxin ingestion Catabolic state High protein intake Large salt and

water intake

between dialysis

GI alkali loss Hemofiltration with

NaCl replacement Ammonium chloride

ingestion

Metabolic alkalosis in ESRD Vomiting Nasogastric drainage Exogenous alkali supplementation

(NaHCO3, KHCO3, CaCO3, Lactate, Acetate, Citrate, Glutamate, Propionate)

Alumimium hydroxide + Na Polysterine sulfonate coadministration

Respiratory disorders in ESRD 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.

Blood gas analysis in ESRD

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.

Clinical implications of acid-base disturbances in ESRD

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

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.

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

Principle of dialytic correction 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)

Bicarbonate fluctuations during HD

Alkali source in HD

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.

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).

Bicarbonate HD (since 1990’s) 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

Other modes of alkali delivery Sorbent cartridge hemodialysis. Hemofiltration. Acetate-free biofiltration.

Acid-base balance during HD

Transmemb. HCO3¯ gradient over time

Dialysiance of HCO3¯

Factors determining HCO3¯ during HD

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.

Management of low HCO3¯ with HD

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 HCO3¯ of approx. 27mM/L once acidosis is controlled.

Only definite way is to measure pre and post HD HCO3¯ levels.

Always look for causes if target not achieved (eg. nutrition, fluid intake, RRF with loss of HCO3¯, loss in stool etc.)

Acid-base balance in special situations

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.

Acid-base balance in special situations

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).

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

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