Ammonia contributes 60%, TA contributes 40 % and HCO3 excretion is almost zero under basal conditions.
Eg. Low HCO3 in ESRD must always be due to met acidosis as respiratory alkalosis cant explain it. Similarly a high HCO3 can only be due to a metabolic alkalosis as a Resp acidosis cant cause this.
“dilution acidosis”. Neither volume addition nor protein catabolism can cause severe acidosis. If HCO3 falls by more than 6-8 acutely=organic acidosis. RTA need not be considered in ESRD.
There is on concept of Cl resistant and Cl sensitive metabolic acidosis in ESRD.
MBD and muscle metabolism: RCT showed that adverse effects if HCO3 less than 19. Similarly 10-15% increase mortality if HCO3 less than 19.
Standard dialysis solution used contains 35-38mM of HCO3.
There is a variation due to the intermittent nature of Rx. Thus it is imp to note when the HCO3 is measured. By convention it is the predialysis value that is measured.
Acetate was immediately metabolised and only after the metab of the residual acetate after dialysis did the HCO3 rise in blood. Toxicity: vasodlation and hypotension.
Uses a sorbent cart which absorbs ammonium ions and replaces H+ which reacts with CO3 to generate HCO3 however, this is not enough and acetate was needed (50-50%0 and caused wide fluctuations.
Organic anions are later metabolised liberating HCO3 and adding to the pool.
This pH control can be seen even at a much lower HCO3 levels. Lactic acidosis by activating PFK
Acid base and control for the dialysis technician
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.
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. Chemical Buffers Respiratory regulatory responses Renal regulatory responses
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)
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
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
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 ¯
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¯
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.
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
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.
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.
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
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 gradientDialysis prescription (fixed) Endogenous acid production (variable)
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).
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
Dialysiance of HCO3¯Transmemb. HCO3¯ gradient over time
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.
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 HCOAlways 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.
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.
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 encephalopathyBiot’s breathing•Medullary injury•Chronic opioid useApneustic respiration•Damage to upper ponsAtaxic respiration•Damage to the medulla oblongata