Renal - Acid Base

Question 1

How do you determine pure vs. mixed metabolic acidosis/alkalosis

Answer 1

Normal value HCO3 = 25
Normal value CO2 = 40

In a pure metabolic acidosis the CO2 should drop by 1 unit for each fall in HCO3 of 1 unit

In a pure metabolic alkalosis the CO2 should rise by 0.7 for each increase in HCO3 of 1 unit

Question 2

How do you determine anion gap?

Which conditions are “Normal anion gap” and which are “raised”

Answer 2

Na - Cl - HCO3
Normal is 12 +/- 2 (10-14)
This accounts for the unmeasured cations (Albumin/Sulfate/PO4 etc.)

If the anion gap is raised this indicates an excessive acid load - Endogenous
Lactic Acid
Keto Acid
Organic Acidemias
Uremia

Exo
Toxic alcohol/glycol
Salicylates
Paraldehyde

If the anion gap is normal this indicates LOSS of BICARBONATE with compensatory high Chloride 
I.e Renal Acidification defects
 Prox RTA
Distal RTA
Renal Failure

HCO3 loss
Diarrhoa
Small bowel losses
CF

Or Chloride infusion

Question 3

How do you determine osmolar gap?

When would you calculate?

What conditions have a high osmolar gap?

Answer 3

Indicated in HAGMA

Osmolar - Measured via freezing point modification

Estimated = (Na x 2) + Glucose + Urea

Normal is 10 and indicates the measured acid does not have a large osmolar effect (i.e. salicylates)

Elevated Osmolar gap indicates that measured acid is highly osmolar - i.e. Ethanol/Methanol/Polyethylene Glycol

Question 4

Acid Load daily?

How is acid base controlled?

Answer 4

Daily 1mmol/kg/day

Controlled by

1) Buffers
2) Respiratory compensation
3) Renal Control (complete by 5-7 days)

Question 5

Describe the different RTAs

Answer 5

Named in order of discovery - not anatomical

So RTA 1 is Distal URINE Not overly acidic - pH > 6.0
RTA 2 is proximal - URINE pH <5.5 i.e. acidic urine because fine tuning occurs distally
RTA 4 is hyperkalemic

So first discovered - was alkalotic urine despite acidotic child - easy to determine that kidneys at fault, fault at end of tubule

When Acidotic - Kidneys MAKE Ammonia (NH3) in PROX then accept H in DISTAL to excrete NH4+

Fine tuning with aldosterone in distal collecting

RTA are single gene nonsense/acquired/medications

Question 6

Fractional Excretion

Answer 6

Fractional Excretion = (( (Urinary solute/Serum Solute) // (Urinary Creatinine/Serum Creatinine) )) x 100

Normal fractional excretion of Na when hyponatremic is <1% i,e it’s all resorbed

Question 7

Proximal Tubule Function?

What happens when disrupted/

Answer 7

Bucket Chemistry
Sucks up as much as it can
Therefore proximal tubulopathy messes with everything

RESORPTION OF:
Na 70%
K 30-50%
HCO3 70%
AA 100%

//
“Global failure of proximal tubule” = RENAL FANCONI SYNDROME
Failure is 
Metabolic Acidodsis
low molecular weight protein/AA loss (Not albumin because glomerular function maintained)
Glycosuria 
Hypoelectrolytes
Hyperphosphaturia - rickeets

Question 8

Proximal RTA Causes?

Answer 8

Proximal RTA - discovered later so TYPE 2

Distal urinary acidification remains intact so urine is acidic (because ammonium) despite renal losses of HCO3

Proximal RTA
Idiopathic
Sjogren’s
Carbonic Anhydrase inhibitors

Proixmal Renal Tubular Failure - Renal Fanconi
Cystinosis - most common
(1 in 100,000 - 200,000
Cystonisin is CTNS on Chr 17
Autosomal Recessive

Multiple types

Defective transport, build up of cystine - kidneys first because they absorb so much protein
Also eyes/gonads
-> CKD)

Rx - reduce cystine load
Supplement electrolytes
GFR reduction
QID Cysteamine or Mercaptamine (body odour/bad breath, allergy) NOT MERCAPTOPURINE- clears cystine out of lysosome
and Q 2 hrly eye drops
//
Metabolic
Single gene stuff

Drug induced - Ifosfamide, Cysplatin, Lead, Mercury

Question 9

What is urine net charge

When calculate a urine osmolar gap?

Answer 9

Ammonium of production in urine calculates kidneys ability to handle acid load

Cl = Na + K + NH4+
NH4 = Cl - Na - K

NH4 + = Net charge should be POSITIVE in setting of systemic acidity to demonstrate normal function

i.e. - if chloride is higher than Na and K then ammonium is present in urine - that is normal urinary acidification (Physiologically intact)

If chloride is lower, impaired urinary acidification

Question 10

Hyponatermic // Hyperkalemic Acidosis?

This FINGERPRINT indicates?

Answer 10

If very early - ?CAH - AKA ALDOSTERONE FAILURE -

Pseudo-hypoaldosteronism FINGERPRINT

TYPE 4 RTA describes physiology)
(Maybe due to distal nephro damage due to pre-existing post-renal/obstructive )

ALDOSTERONE tells tubules to Dump acid, dump potassium, retain sodium

Rx effect of spironolactone

Also - HYPERALDOSTERONISM

• Hypertensive
• High Na (obscured by water retention)
• Low K
• Alkalotic

Question 11

H+ and K+ always move:

Answer 11

Together in and out of cells - if acidotic blood also high K+ as per DKA
Need heaps of K as correct acidosis

If vomiting HCl
Then also low K

Question 12

Metabolic Alkalosis

Chloride Repsonive

Chloride Resistant

Answer 12

Chloride responsive are non-intrinsic
(Vomiting/Diuretics)

Resistant are intrisinc defects of physiology

Question 13

Which one is BARTTER syndrome?

Answer 13

Autosomal Recessive
1 in 50,000-1:100,000
Resembles Chronic Frusemide Administration

Plenty of different genes - therefore heterogenous presentation
May be neonatal

NKCC2
ROMK
CLC-Kb

Massive loss of Na and K
High Calcium:Creatinine ratio

Massive polyuria

LOOP OF HENLE

Treat with high dose NaCl/KCl
Indomethacin to reduce GFR (Iatrogenic to reduce renal losses)

Question 14

Which one is Gittleman

Answer 14

Chronic Thiazide Diuretic
Alkalotic
Hypokalemia
Intractable Hypomagnesemia
Hypocalciuria
Hyperreniinaemic normotensino

Gene SLC12A3 or the WNK (with no kinase)