Electrolyte and Acid-Base

Disturbances

Rahul Sud

Renal Advanced Trainee

Dr Martin Gallagher

Head of Department, Renal Medicine

CRGH

Case 1

• ME, 56 yo F BIBA

– Found by neighbour- confused state at home

– Feeling unwell 3/7

– Nauseated and vomiting

– No abdominal pain

Background

• ESRF- HDx x3/week- in centre via vascular catheter

• IHD

• CCF- EF 25-30%

• Previous VF hyperkalemic arrest

• Type 1 DM– Erratic BSLs

– Gastroparesis

– Micro/macrovascular complications

• HTN

• Hypercholesterolemia- statin myopathy

Medications

• Levemir 20/28 units

• Humalog 6/8/10 units

• Nurofen weaning (recent crystalline arthropathy)

• Carvedilol 3.125mg BD

• Clopidogrel/Aspirin 75/100mg

• Pantoprazole 20mg

• Rosuvastatin 10mg

On Examination

• BP 145/50

• HR 100

• 99% RA

• RR 22- Kussmaul Breathing

• T362

• Confused, GCS 14

• HSDNM, Chest clear, JVP 4cm, +pedal edema

• Abdomen soft, non tender

• Limited neurological examination normal- tone and reflexes

• Rt tunelled IJ vascular catheter- exit site clear

• Rt foot- swelling 1st MTP gout

Investigations

• Na 119

• K 7.3

• Cl 77

• HCO3 10

• Urea 20.1

• Creat 331

• Glucose 65

• HbA1c 13.6%

• Blood Ketones 6.4

• ABG- RA

– pH 7.13

– PaO2 95

– PaCO2 22

– HCO3 9

– BE -19

– Lactate

3.0mmol/L

• LFTs normal

• Ca 2.55

• Mg 1.05

• PO4 2.5

• Hb 146

• WCC 8.8

• Plt 417

• CRP 12.4

Next Investigation??

ECG

Hyperkalemia- Consequences

• Muscle Weakness- Parasthesia, mild

motor paralysis, paraparesis, ascending

paraplegia

• ECG Findings- shortening of QT, peaking

of T waves, QRS prolongation, shortening

of PR interval, loss of SA conduction

“sine wave” rhythm

Hyperkalemia- Consequences

• Mortality

– Poor correlation between serum K and

cardiac manifestations

– Observational studies in patients, CKD Stage

3 -5 have shown that K concentrations 5.5 –

5.9 are not associated with increased rates of

mortality

Returning to Our Patient

• Cause of metabolic acidosis

– Ketoacidosis

– Uremic acidosis

• Diabetic Ketoacidosis

– Admitted Under Endocrinology- ICU

– Intravenous Fluids

– Insulin infusion

– Haemodialysis next day (?)

• Electrolyte Management

• Fluid management

• Other

• Collaborative history- high BSLs several days- “forgot

her insulin”

Repeat Bloods

3 Hours Later

• Na123

• K 5.4

• Cl 83

• HCO3 11

• Urea 20.5

• Creat 335

• Glucose 61

5 Hours Later

• Na125

• K 4.9

• Cl 89

• HCO3 14

• Urea 19.5

• Creat 334

• Glucose 56

Next Day

• Na136

• K 4.0

• Cl 99

• HCO3 18

• Urea 19.2

• Creat 354

Progress

• Stabilised on insulin regimen with weekly

endocrine follow up post dialysis

• Continuing x3/week in-centre dialysis-

plans to create AVF.

Case 2

• AC 61 yo F

– Vomiting and diarrhea 4/7

– Opening bowels x4/day, nil blood/mucus

– Unable to tolerate oral intake

– No abdominal pain or fevers

Background

• Type II Diabetes Mellitus- Oral Hypoglycemics

• Hypertension

• Refractory Hyperlipidemia- commenced Krill Oil

capsules 1/52 prior to presentation

• Fe Defficiency Anemia- recent capsule

endoscopy- scattered flecks of blood in small

bowel

• CKD Stage 3A- arteriolar nephrosclerosis

– Baseline Creat 110, eGFR 48

Medications

• Metformin 1g BD

• Krill Oil capsule 1 daily

• Rosuvastatin 40mg nocte

• Aspirin 100mg daily

• Lercanidipine 20mg daily

• Caltrate one daily

• B12 injections

On Examination

• BP 115/55

• HR 100

• 96% RA

• T 359

• BSL 7.2

• UO 80ml/hour

• UA– pH 6.0, +blood,

++ketone, ++glucose, nil protein

• Alert and oriented

• Looks dry

• Normal

cardiorespiratory

examination

• Abdomen soft,

epigastric

tenderness

• No rashes

• Your Thoughts?

Investigations

• Na 138

• K 6.7

• Cl 92

• HCO3 <10

• Urea 40.5

• Creat 937

• AG- 40

• ABG– pH 7.17

– PaO2- 124

– PaCO2- 18

– HCO3- 6

– BE- -20

– Lactate 9.5

• ECG– SR, nil acute

changes ↑ K

• LFTs normal

• Lipase 64

• Ca 2.4

• Mg 0.9

• PO4 2.98

• WCC 14.8

– PMN 12.4

– Eosinophil 0.0

• Hb 104

• Plt 405

Issues

• Acute Kidney Injury

• Hyperkalemia

• Metabolic Acidosis

– Multifactorial

Your Management Strategy?

Our Diagnosis

• ?Initial Insult to Kidney

– ?Secondary to Gastroenteritis

– ?Acute Interstitial Nephritis

– ?Obstruction ?Sepsis..

• Metformin Induced Lactic Acidosis

Management

• Cease Metformin, commence Diamicron

• IV Rehydration

• Sodium Bicarbonate,Insulin/Dextrose

• Arrange Rt Femoral Vascular Catheter

– Dialysis- 3 hour session, BFR 150ml/min, heparin 500unit bolus/ 500 units per hour, low K bath, no fluid removal

• IDC

• ICU Admission

Repeat Bloods

• 3 Hours Later

• Na142

• K 5.8

• Cl 96

• HCO3 <10

• Urea 39.4

• Creat 890

• Following Dialysis

• Na139

• K 4.0

• Cl 102

• HCO3 20

• Urea 18.4

• Creat 435

• ABG

– pH 7.42

– paO2 75

– paCO2 32

– HCO3 20

– BE -4

Progress

• Persistent Renal Impairment- Creat 600

• Renal Biopsy- florid tubulointerstitial

nephritis highly suggestive of drug

aeitiology (likely culprit- Krill Oil capsules)

– Pulsed Methylprednisone x3

– Weaning Dose Prednisone

– 3/12 post admission, Creat 170, eGFR 28

Acid Base Disturbance

• Acid:base homeostasis

• Metabolic acidosis:

– Classification(s)

– Causes

– Treatment approach

Acid:base homeostasis

• Henderson-Hasselbach

• Acid load

• Clinical consequences

• Mitigating factors

– Timing of their effects

• Role of the kidney

• Diagnostic tools

Acid:base disturbance

• Metabolic acidosis:

– Classification(s)

– Common causes

– Management

Acid:base homeostasis

• Importance of buffers

– Bicarbonate the most important

– Proteins and inorganic phosphate contribute

• Henderson-Hasselbach equation

– pH = 6.1 + log10 [HCO3- ]/[0.03 x PaCO2]

– Allows classification:• Numerator: metabolic processes

• Denominator: respiratory processes

• Both: mixed/complex processes

Acid burden

• Approx 1mmol/kg per day

• Fixed vs volatile acids– Fixed only excreted renally

– Volatile via lungs

• Metabolic effects of acidosis (usually below pH 7.1):– Myocardial contractility depressed

– Peripheral resistance falls

– Favourable oxygen delivery

• Clinical effects:– Kussmaul‟s respiration (pH below 7.2)

– Above cardiac and bp effects

– Chronic metabolic acidosis: hypercalciuria and bone disease (bone buffers the acid)

Renal role in acid:base

• Large amount of filtered HCO3-

– 24mmol/L

– GFR of 100ml/min

• Bulk reabsorption

– Proximal tubule

– Using carbonic anhydrase

Collecting duct: Intercalated

Cells

Net acid excretion

• Adding 1mmol of HCL to 1litre of water

– Resultant pH = 3

• Buffers (phosphate) mitigate this fall in pH

• Bulk acid excretion requires a non-

titratable acid: NH3 NH4+

Screen clipping taken: 17/07/2011, 9:35 AM

• Diarrhoea:

– Bicarb concentration usually ~40mmol/L• Much greater than serum

• Other GI losses

– Very high bicarbonate secretion from:• Bile

• Pancreas

• Saliva

– Most delivered into the proximal small bowel

– Kidney pancreas transplant example

• Urinary diversions:

– Bowel mucosa secretion of bicarb in

exchange for chloride

• Renal tubular acidosis

• Carbonic anhydrase inhibitors

• Hypoaldosteronism

– Eg: diabetes

• K sparing diuretics

• Other miscellaneous causes of

hyperchloraemic acidosis

– Dilutional

– HCl administration

– Parenteral feeding, sulfur ingestion

Lactic acidosis

• Lots of causes, common

• Bicarb admin remains topical

– Some evidence for harm

• DKA:

– Urine ketones need to be high

• Other organic acidoses:

– Starvation

– Alcoholic Ketoacidosis

• Treatment of MA

– Underlying cause

Case 1

• 54 yo female

– Nausea, vomiting

– Generally unwell 3

days

– Nil localising symtoms

• PMHx

– MM: poor response to

treatment to this point

– DM: type II

• T: 37.3 bp: 110/70

• RR: 24 HR: 115 Sat:

95%

• Chest: NAD

• Abdo: NAD

• Bloods:

– WCC: 6.7 HB: 112 Pl: 187

– K: 5.2 HCO: 10 Ur: 7.6 Cr:

140

Case 1 cont

• ABG:

– pH: 7.32

– O2: 86

– CO2: 23

• What will happen

next?

• ABG (2)

– pH: 7.18

– O2: 62

– CO2: 36

Case 2

• 70 yo male– ED with dizziness,

vomiting & confusion

– Gradual onset last 2 weeks

• PMHx– COPD

• Low dose home oxygen

– Hypertension

– IHD:• AMI 6 y ago

• T: 36.8 bp: 115/60

• RR: 26 HR: 100 Sat: 91%

• Chest:– Reduced expansion & BS

– Soft HS, mild MR

• Abdo:– NAD

• Bloods:– Na: 133 K: 3.0 HCO: 39

– Ur: 3.6 Cr: 120

Case 2 cont

• ABG:

– pH: 7.53

– O2: 58

– CO2: 60

• Thoughts?

• Treatment?

Metabolic Acidosis in CKD

• Reduced renal mass- failure of tubular acidification processes to secrete the normal daily acid load

– Each remaining nephron shows adaptive increases in H+ secretion and ammonia production

• Initially a normal anion gap metabolic acidosis, but in end stage with progressive inability to excrete phosphates, sulfatesetc... classic high AG „uremic acidosis‟

Metabolic Acidosis in CKD

• A very common problem in both the

dialysis and predialysis population1

1. Sterns et al. Fluid, Electrolyte and Acid-Base Disturbances. NephSAP July 2007.

Difficulties Interpreting Serum

Bicarbonate• Low Bicarbonate

– Excellent nutrition: higher protein intake

generating a larger acid load (predicts better

survival)

– Systemic inflammation (predicts poorer

survival)

?Best bicarbonate level to predict survival

Effects of Metabolic Acidosis in

CKD• Increase protein catabolism

• Bone resorption

Treatment

• Sodium Bicarbonate

– KDOQI and CARI recommend serum HCO3 >22• Improves protein metabolism, nitrogen balance, nutritional

parameters, muscle function and bone density.

• Slows progression of chronic renal disease1

– Controversial

– Plausible mechanisms by which MA can be harmful

» Harm: Increased ammonium related nephrotoxicity by activation of alternative complement cascade2

• Caltrate vs Sevalmer as phosphate binder

– Sevalemer hydrogen chloride associated with reduced serum bicarbonate concentrations

1. De Brito-Ashurst et al. Bicarbonate supplementation slows CKD progressions and improves nutritional status. JASN 2009

2. Nath et al. Pathophysiology of chronic tubulointerstitial disease in rats: interactions of dietary acid load, ammonia and

complement C3. J Clin Inv 1985

Lactic Acidosis

• Lots of causes- broadly divided into

– Type A- tissue underperfusion and/or hypoxia• Lactic acid only accounts for small fraction of AG

– Type B- absence of tissue underperf/hypoxia

• Treatment Type A LA- correct the underlying disorder

– Role of bicarbonate is controversial• Experimental models and clinical observations that bicarb

may depress cardiac function and exacerbate acidemia. Other issues- Volume load and rebound alkalosis

• Role in severe acidemia (pH threhold)?– Lack of guidelines and agreement between physicians

DKA

– Need evidence of acidosis and ketones

– Treatment: Insulin and IV fluids

– Insulin levels required to turn off ketogenesis

much lower than those required to lower

glucose

– Bicarb treatment probably not indicated, as

insulin leads to metabolic conversion of

ketoacid ions to HCO3

• ?Role in Cardiac Dysfunction

• ?Role with severe acidosis- pH <7.1

Metformin Associated Lactic

Acidosis (MALA)• 90% oral dose of metformin excreted by

kidneys- usually very efficient at removal

• MALA Uncommon (0.03 cases/1000 patient years)

• Difficult diagnosis- exact aeitiological role played by metformin in the development of LA often remains uncertain– Three broad settings where it can occur

• Inappropriate prescription of metformin to patients with ESRF

• Patients develop AKI and continue to take the drug

• Overdose

• Mechanism: High metformin concentration binding to

mitochondrial membranes blocks oxidative phosphorylation.

Metformin Associated Lactic

Acidosis (MALA)

Metformin Associated Lactic

Acidosis (MALA)• Treatment

– When presenting with

presumed metformin

toxicity, efforts to

remove metformin are

indicated

• Metformin not protein

bound: dialysable

• Need for prolonged

periods given large

volume of distribution

Thank You!