Acid base conference

Lama Nazzal

Case

• 24 y/o quadraplegic M admitted on 12/24 with MVA , complete C5-C6 cervical transection and R vertebral artery dissection with worsening alkalosis.

• On 12/26, the pt had an asystolic episode requiring 15sec of compressions, atropine and epi and was intubated.

• Etiology was thought to be due to respiratory failure and inability to clear secretions.

• Pt had trach performed in OR on 12/28 followed by posterior reduction, instrumentation and fusion.

• Had high fevers (over 104) and RLL infiltrate early in hospital course with desats despite high FiO2, CXR/CT with extensive consolidation all consistent with ARDS.

case

• On 1/18, the pt was found to have a L PTX on CXR requiring chest tube placement, which was complicated by persistent air leak.

• Pt vent dependent and required multiple bronchoscopies for suctioning of secretions.

• Patient was given Lasix IV PRN for fluid overload

Case

• Medications:

• Amikacin, Ciprofloxin

• Ascorbic Ac, Aspirin, Docusate, Enoxaparin, Epogen

• Escitaloprm, Esomeprazol

• Ferrous SO4

• Folic Acid

• Humulin R

• Metamucil, Mg Oxide, MVI

• PRNs: Acetaminopn, Albuterol, Temazepam, lasix

• Vitals Signs:

Tm 101.5 , HR97-110 , MAP 78-95 RR 16-22 SaO2 91-97 Vent Settings: BiLevel 30/0. FiO2 70%, PS 40, rate 17 I/O: 2580/4511

• Exam Findings:

• General: trach in place on vent, sedated after bronchoscopy

• Neck: trach in place

• Heart: tachycardic, regular rhythm no murmurs auscultated

• Lungs: vented breath sounds anteriorly

• Abdomen: pitting abdominal wall and sacral edema

• Extremities:warm and dry, mild edema

Labs:

• Na: 134

• K: 4.1

• Cl: 83

• CO2: 54

• Cr<0.1

• 7.40/81.4/80 lact:1.2

Na K Cl CO2 BUN Cr

When KCl started

Discharge labs:

Does volume depletion cause metabolic alkalosis ?

• In this first study by Cannon et al. in 1965 on 4 patients diuresed with ethacrynic acid, alkalosis was observed.

• Patient were on low Na and Cl diet.

• The hypothesis was that extracellular fluid (ECF) volume decrease produces alkalosis by loss of relatively bicarb free fluid in the urine.

CannonPJ et al. Ann Intern Med 62: 979–990, 1965

• Metabolic alkalosis was induced in dogs by administering ethacrynic acid and sustained by feeding a chloride-deficient diet.

• Then ECF volume was expanded "isometrically,”

• Met alkalosis was corrected by 24 hours without an increase in GFR, despite increasing potassium depletion

• It was attributed to the selective retention by the kidneys of chloride from the administered solution.

Cohen JJJ Clin Invest 47: 1181–1192, 1968

The volume hypothesis

During ECF volume depletion:

• Increase fluid reabsorption in the proximal tubule.

• Bicarbonate is preferentially reabsorbed compared with chloride

• Alkalosis is maintained.

During correction:

• volume expansion decreases proximal tubule fluid reabsorption

• More bicarbonate is delivered to the distal nephron, which has a limited capacity to reabsorb bicarbonate.

• Increase in urine Bicarb and correction of alkalosis

• Schwartz et al . studied the pathogenesis of chloride depletion alkalosis (CDA) in men and dogs.

• Gastric aspiration, chloruretic diuresis, NaNO3 infusion, and prior hypercapnia were used to generate CDA.

• All studies established that Cl repletion by NaCl or KCl fully corrects CDA in the maintenance phase.

Schwartz WB et al.Am J Med 64: 417–428, 1978

Volume and CDA

• Galla et al studied the effect of Cl repletion with no volume expansion in rat models of CDA induced by Peritoneal dialysis against 0.15 M NaHCO3.

• They showed that rats given Cl drink with either Na+ or choline had complete correction of CDA despite negative Na+ and K+ balances, decreased body weight, and obligatory sodium or choline bicarbonate loading.

• Rats with CDA maintained for 7– 10 days had a similar response

• Alternatively, CDA rats were infused with 5%dextrose with either 6%albumin or an isometric Cl solution. CDA persisted in rats infused with albumin despite 15%ECF volume expansion, but was corrected by the Cl containing solution despite persistent volume depletion and decreased GFR.

Diuretic induced Cda

Rosen et al.Am J Med 84: 449–458, 1988

PCT vs DCT

• Galla et al. showed that absolute bicarb reabsorption in the proximal convoluted tubule was similar in control and CDA groups whether volume contracted or expanded and whether maintaining or correcting CDA and was positively correlated with the filtered bicarb load.

• Absolute net bicarb reabsorption in the loop segment of these superficial cortical nephrons was not significantly greater in alkalotic rats, whether correcting or maintaining CDA, than that in control groups.

• Levine et al.showed that in DCT chloride-free perfusates inhibit bicarbonate secretion and enhance bicarbonate reabsorption, while high chloride perfusates elicit net bicarbonate secretion.

• The magnitude and direction of bicarbonate transport is dependent upon the degree of alkalosis and chloride repletion in vivo at the time of tubule harvesting.

Galla JH et al. Am J Physiol 257: F107–F113, 1989 Levine DZ et al. J Clin Invest 85: 1793–1798, 1990

PEndrin

• Pendrin (SLC26A4) has been identified as the apical chloride/bicarbonate exchanger expressed by type b and non a-non b intercalated cells and both pendrin expression and subcellular localization are regulated by changes in acid/base status

• It is a member of the solute carrier family 26 (SLC26) which is a group of multifunctional anion transporters.

• SLC26 family plays a physiological role in almost all organ systems, functioning in the transport of anions such as sulfate iodide, formate, oxalate, Cl , hydroxyl and HCO3.

Pendrin and met acidosis

Purkerson JM et al. Kidney Int 78: 993–1005, 2010

Pendrin and Cl restriction

Verlander JW et al. Am J Physiol Renal Physiol 291: F833–F839, 2006

.

NaCl-replete diet

Na-replete, Cl- restricted diet

Pnd in apical vesicles

Pnd in apical mne

type B intercalated cells

non-A, non-B intercalated cells

NaCl-replete diet

Na-replete, Cl- restricted diet

Pnd in apical vesicles and mne

Pnd in apical vesicles

Pendrin KO

Amlal H et al. Am J Physiol Cell Physiol 299: C33–C41, 2010

Pendred syndrome

• Pendred syndrome is caused by the mutations of pendrin gene.

• First described in 1896 when Vaughan Pendred first described an Irish family in which 2 of 10 children suffered from congenital deafness and goiter.

• Human with Pendred syndrome seem to have normal acid-base status.

• However, two recent cases of a severe metabolic alkalosis occurring in a child, given thiazide and in an adult in response to vomiting, were described.

Thank you