Henderson-Hasselbalch Equation

Most accurate, but requires log calculator

pH = 6.1 + log10([HCO3-]/(0.03 x PCO2))

+] = 24 x PCO / [HCO -]
[HPCO2 is in mm Hg 2 3
[HCO3-] is in mEq/L

pH = -log10[H+]

Nephrology & Hypertension 1

LSUHSC
Time course of buffering/Compensation
Distribution and extra- Cell
Cellular buffering Respiratory
buffering compensation Renal H+
100
secretion

50

H+
Load
0 6 1 2
 Reabsorption
How much bicarbonate is filtered
everyday?
• Normal plasma HCO3
concentration is 24 mmol/L
• Normal GFR is 100 mL/min, or
0.1 L per minute
• 1440 minutes in a day
• 24 × 0.1 × 1440 =

3,456 mmol of bicarbonate are

filtered a day (filtered load)
Bicarbonate Synthesis
How much bicarbonate needs to be replaced?
How much acid is consumed?
The daily acid load
• Protein metabolism
– 1 mmol/kg
Bicarbonate must be
replaced to maintain
homeostasis
19 y.o.
superhero
with fatigue
Severe 33
hypokalemi 138 84
a 2.7 44
Denies the 1.0
use of 7.57 / 52 / 96 / 42
diuretics,
laxatives
 Steps to Success
1.Check the pH
2.Determine the primary acid base
process

Nephrology & Hypertension 6

LSUHSC
Determine the primary disorder
7.57 / 96 / 52 / 42
pH / pO2 / pCO2 / HCO3

1. Acidosis or alkalosis
– If the pH is less than 7.4 it is acidosis
– If the
the pH
pH is
isgreater
greaterthan
than7.4
7.4it it
is is
alkalosis
alkalosis

2.
–
Metabolic Alkalosis
Determine if it is respiratory or metabolic
If the
the pH,
pH, bicarbonate
bicarbonateandand pCO
pCO
2 all
2 all
move
move
in the
in the
same
same
direction
(up or down)
direction (upitor
is down)
metabolic
it is metabolic
– If the pH, bicarbonate and pCO2 move in discordant directions
(up and down) it is respiratory
and down) it is respiratory
32 y.o. female with fatigue, weakness and muscle
aches

139 115 16
7.34 / 33 / 87 / 18
3.1 17
1.0
Determine the primary disorder
7.34 / 87 / 33 / 16
pH / pO2 / pCO2 / HCO3

1. Acidosis or alkalosis
– If the
the pH
pH isisless
lessthan
than7.4
7.4it itis is
acidosis
acidosis
– If the pH is greater than 7.4 it is alkalosis
2. Determine if it is respiratory or metabolic
–
Metabolic Acidosis
If the
the pH,
pH, bicarbonate
bicarbonateand
(up or down)
direction (upitor
is down)
andpCO
metabolic
pCO
2 all
2 all
move
it is metabolic
move
in the
in the
same
same
direction

– If the pH, bicarbonate and pCO2 move in discordant directions

(up and down) it is respiratory
 Steps to Success

1.Check the pH
2.Determine the primary acid base
process
3.Check for compensation
(Simple/Mixed)

Nephrology & Hypertension 10

LSUHSC
 Determine the degree of compensation
METABOLIC ACID: PCO2 = 1.5 HCO3 + 8
MIN PCO2 = 10 mmHg

METABOLIC ALK: 10 mEq/L  HCO3  6 mmHg  PCO2

MAX PCO2 = 55-60 mmHg

ACUTE RESP ACID: 10 mmHg  PCO2  1 mEq/L  HCO3

MAX HCO3 = 30-32 mEq/L

CHRON RESP ACID: 10 mmHg  PCO2  4 mEq/L  HCO3

MAX HCO3 = 45 mEq/L

ACUTE RESP ALK: 10 mmHg  PCO2  2 mEq/L  HCO3

MIN HCO3 = 18 mEq/L

CHRON RESP ALK: 10 mmHg  PCO2  4 mEq/L  HCO3

MIN HCO3 = 12-15 mEq/L
Nephrology & Hypertension 11
LSUHSC
 Predicting pCO2 in metabolic
acidosis: Winter’s Formula
• In metabolic acidosis the expected pCO2 can be estimated
from the HCO3

Expected pCO2 = (1.5 x HCO3) + 8 ± 2

• If the pCO2 is higher than predicted then there is an

addition respiratory acidosis
• If the pCO2 is lower than predicted there is an additional
respiratory alkalosis
32 y.o. female with fatigue, weakness and muscle
aches

139 115 16
7.34 / 33 / 87 / 18
3.1 17
1.0
 Is the compensation appropriate?

7.33 / 87 / 33 / 17
pH / pO2 / pCO2 / HCO3

• Expected pCO2 = (1.5 x HCO3) + 8 ±2

 Is the compensation appropriate?

7.33 / 87 / 33 / 17
pH / pO2 / pCO2 / HCO3

• Expected pCO2 = 31-35

• Actual pCO2 is 33, which is within the predicted range, indicating

appropriate respiratory compensation
Is the compensation appropriate?

7.33 / 87 / 33 / 17
pH / pO2 / pCO2 / HCO3

Appropriately compensated
metabolic acidosis
• Metabolic acidosis is further evaluated by determining
the anion associated with the increased H+ cation
• In medicine we categorize the anions into:
chloride not chloride

Non-Anion Gap Anion Gap

Metabolic Acidosis Metabolic Acidosis
…and differentiate the two based on the anion gap.
ANION GAP
SO4
160 Mg
PO4
K
Ca ORGANIC ANIONS
ALBUMIN
Anion GAP
120 ALBUMIN
HCO3

HAGMA
NAGMA
mEq/L

80
Na Cl

40

0
CATIONS ANIONS
Nephrology & Hypertension 18
LSUHSC
Anion gap

=
Anion gap

Goldmark
Mudpiles
Plumseeds
Calculating the anion gap
139 115 16
3.1 17
1.0
• Anion gap = Na
139––(HCO
(17 +3115)
+ Cl)

Appropriately compensated
• Normal
Anion gap
is 12
=7
– Varies from lab to lab

non-anion gap metabolic acidosis

– Average anion gap in healthy controls is 8 ±4
• Improving chloride assays have resulted in increased chloride
levels and a decreased normal anion gap.
Non-anion gap metabolic acidosis NAGMA

Focus on RTA
 NAGMA

Chloride intoxication GI loss of HCO3 Renal loss of

Dilutional acidosis Diarrhea HCO3
HCl intoxication Surgical drains Renal tubular acidosis
Chloride gas intoxication Fistulas Proximal
Ureterosigmoidostomy Distal
Early renal failure
Obstructed Hypoaldosteronism
ureteroileostomy
 pH = 5.5
Cl = 154 mmol/L

Plasma volume
3 liters
3L Bolus Saline = 154 x 3 (466 meq)
Plasma Cl = 105
Rise in Cl will be 6-9 meq
Drop in HCO3 3-6 meq
 NAGMA

GI loss of HCO3
Chloride intoxication Diarrhea
Renal loss of
Dilutional acidosis HCO3
Surgical drains
HCl intoxication Renal tubular acidosis
Fistulas
Chloride gas intoxication Ureterosigmoidostomy
Proximal
Early renal failure Distal
Obstructed ureteroileostomy
Hypoaldosteronism
Cholestyramine
 140 102
Plasma
4.4 24
Bile
135 100
5.0 35
135 50
Pancreas
5.0 90
135 50
Small intestines
5.0 90
Large intestines
110 90
Urinary diversion
• Urine NH4+ is absorbed by the intestinal mucosa and
converted to H+ and NH3.

• Urine Chloride stimulates colonic expression and

activation of Cl-/HCO3- exchangers exacerbating the
loss of bicarbonate.

• Increased colonic pressures can cause urinary

obstruction resulting in a urinary acidification defect

– Repeated episodes of pyelonephritis may do the same

 NAGMA

Renal loss of
Chloride intoxication GI loss of HCO3
Dilutional acidosis Diarrhea
HCO3
HCl intoxication Surgical drains Renal tubular acidosis

Chloride gas intoxication Fistulas Proximal

Ureterosigmoidostomy Distal
Early renal failure
Obstructed Hypoaldosteronism
ureteroileostomy
 Renal causes of NAGMA:
Renal Tubular Acidosis (RTA)
RTA can be due to a failure of the kidney
to
1. Reabsorb all of the filtered bicarbonate
2. Synthesize new bicarbonate to
replace bicarbonate lost to metabolism
3. Stow hydrogen ions in ammonia so we can
clear the daily acid load
 3 steps in
renal
bicarbonate
3456 mmol/day handling
50-100 mmol/day
 Each step can fail
which causes RTA

2 1
3456 mmol/day
and
NAGMA

4
Proximal RTA
50-100 mmol/day
Distal RTA

Hyperkalemic RTA
 Proximal RTA (Type 2)
• The Tm is the maximum plasma
concentration of any solute at which
the proximal tubule is able to
completely reabsorb the solute.

• Beyond the Tm the substance will Na+

be incompletely reabsorbed and H2O Amino Acids
spill in the urine. HCO3 Glucose

• In Proximal RTA the Tm for

bicarbonate is reduced from 26 to
15-20 mmol/L.
Proximal RTA (Type 2)
Damage to the proximal 24 mmol/L
tubule decreases its Tm
from 28 to somewhere in
the mid-teens
15 mmol/L
Tm for HCO3 at 15

Serum HCO3 is > Tm

so HCO3 spills into pH 8
the urine
Proximal RTA (Type 2)
Serum HCO3 then falls 15 mmol/L

When it falls to the Tm

(15 mmol/L) the kidney
appears to work 15 mmol/L

normally
Homeostasis resumes
but at a decreased pH 5
Proximal RTA (Type 2)
If the patient 12 mmol/L

encounters an acid
load, they synthesize
new bicarbonate to
12 mmol/L
return the serum
HCO3 to altered Tm
(15)
pH 5
Proximal RTA (Type 2)
20 mmol/L
During treatment with
exogenous
bicarbonate the serum
bicarbonate will rise
above the Tm and the15 mmol/L
patient will spill
bicarbonate
pH 8
Proximal RTA: etiologies
Acquired Genetic
Acetylzolamide Cystinosis
Ifosfamide Galactosemia
Multiple myeloma Hereditary fructose intolerance
Lead toxicity Wilson’s disease
Chronic hypocalcemia Chronic respiratory
Cisplatin
alkalosis
Mercury poisoning
Streptozocin Intracellular alkalosis
Expired tetracycline
 Proximal RTA:
consequences
• Loss of potassium
(hypokalemia)
• Bone disease
– Bone buffering of the
acidosis

• Decreased growth
• Not typically
complicated by stones
 Each step can fail
which causes RTA

2 1
3456 mmol/day
and
NAGMA

4
Proximal RTA
50-100 mmol/day
Distal RTA

Hyperkalemic RTA
 Distal RTA
H+ Secretion
Congenital
Pyelonephritis
Sickle cell anemia
Sjögren’s
syndrome/Lupus
Lithium/Ibuprofen
Toluene (Glue sniffing)
Wilson’s disease
 Distal RTA
Gradient defect

Amphotercin B
 Distal RTA
Voltage
dependent
Only variety of distal RTA
which is hyperkalemic
Differentiate from type 4 by
failure to respond to
fludrocortisone
Obstructive uropathy
Sickle cell anemia
Lupus
Triameterene (Bactrim)
Amiloride
 Distal RTA: Consequences
Bones Kidney stones
Chronic metabolic Calcium phosphate
acidosis results in stones
bone buffering • Hypercalciuria
• Phosphate • Increased urine pH
• Calcium • Decreased urinary
citrate
 Each step can fail
which causes RTA

2 1
3456 mmol/day
Proximal RTA
and NAGMA

4
50-100 mmol/day
Distal RTA

Hyperkalemic RTA
 Chronic hyperkalemia of any etiology decreases
ammoniagenesis

• NH3 is needed to
excrete excess
H+ in the urine
ammonia

Intracellular alkalosis suppresses intra-renal

ammonia With increases in
serum potassium,
potassium shifts
inside the cells
Intracellular
alkalosis To maintain
electroneutrality, H+
moves out of the
cells
 Hypoaldosteronism: Type 4
• Chronic hyperkalemia
decreases ammoniagenesis

• Without ammonia acid

excretion is modest

• Urinary acidification is intact

• Acidosis is typically mild

without significant bone or
stone disease

• Primary problem is high

potassium
 Diagnosing
non-anion gap metabolic acidosis
To look for renal H+ clearance
look for urinary ammonium

+
NH4
Ammonium

Titratable acid
Urinary anion gap: (Na+ + K+) – Cl–
Urinary ammonium detector
• In the presence of ammonium the
chloride will be larger than the sum
of Na and K.
• So a negative anion gap means
ammonium in the urine.
• Ammonium in the urine =
effective renal acid secretion
• Ammonium in the urine usually rules
out RTA
Urinary anion gap: (Na+ + K+) – Cl–
Urinary ammonium detector
• In the absence of ammonium the Na
and K will be larger than the
chloride.
• So a positive anion gap means no
ammonium in the urine.
• No ammonium in the urine = no
effective renal acid secretion,
regardless of the urinary pH
• A positive urinary anion gap in the
presence of metabolic acidosis is
 NAGMA and urinary anion gap
• Diarrhea
– Negative 24 mmol/L
15
12
• Proximal RTA
– At baseline
• Negative (variable)
– During treatment
• Positive
15 mmol/L
12
– During acid load
• Negative
• Distal RTA:
– Positive
pH 8
• Type IV RTA
pH 5
– Positive
32 y.o. female with fatigue, weakness and muscle
aches

139 115 16
7.34 / 33 / 87 / 18
3.1 17
1.0
 139 115 16 U/A pH 6.5
3.1 17
1.0 Urine electrolytes

80 115
7.34 / 87 / 33 / 16
45
Appropriately compensated non-anion gap
metabolic acidosis due to distal RTA
74 y.o. female with 34 year
history of DM c/o weakness

21 7.34 / 38 / 92 / 16
139 123
6.6 17 Albumin 1.8
1.2
Determine the primary disorder
7.28 / 38 / 92 / 16
pH / pCO2 / pO2 / HCO3
1. Acidosis or alkalosis
– If the
the pH
pH isisless
lessthan
than7.4
7.4it itis is
acidosis
acidosis
– If the pH is greater than 7.4 it is alkalosis

2. Determine if it is respiratory or metabolic

–
Metabolic Acidosis
If the pH, bicarbonate and pCO2 all move in the same direction
(up or down) it is metabolic
– If the pH, bicarbonate and pCO2 move in discordant directions
(up and down) it is respiratory
Predicting pCO2 in metabolic
acidosis: Winter’s Formula

7.23 / 38 / 92 / 16
pH / pCO2 / pO2 / HCO3

Combined metabolic acidosis

– Expected pCO2 = (1.5 x HCO3) + 8 ±2
– Expected pCO2 = 31-35
and respiratory acidosis
– Actual pCO2 is 38, which is higher than predicted, so
the patient has an additional respiratory acidosis
Calculating the anion gap

139 123 16
6.6 17
• Anion gap = 139
Na ––(HCO
(123 3++17)
Cl) 1.0
A negative anion gap!
• Anion gap = -1

That’s got to mean something!

Other causes of a low anion gap
• Increased chloride
– Hypertriglyceridemia Sodium Chloride
– Bromide Bicarb
– Iodide
• Decreased “Unmeasured anions”
– Albumin
– Phosphorous Albumin
– IgA Normal Phos
Anion gap
• Increased “Unmeasured cations” IgA
– Hyperkalemia
Potassium
– Hypercalcemia
– Hypermagnesemia Calcium
– Lithium Magnesium
– Increased cationic paraproteins IgG
• IgG
Calculating the Urine anion gap
139 123 16 U/A pH 6.0
6.6 17 70 95
1.0
• Anion Na –= (HCO
15
Urine anion
gap = gap 3 +–
(70+15) Cl)
95
A negative Urine anion gap!
• Anion gap = -10

That’s means low NH4+

 non-anion gap metabolic
acidosis with hyperkalemia

1. Type four RTA, 2. Hyperkalemic Distal (Type 1)

hyporenin-hypoaldo RTA, voltage dependent distal
RTA
Aldosterone will be high in Voltage related
 Distal RTA
Voltage
dependent
Only variety of distal RTA
which is hyperkalemic
Differentiate from type 4 by
failure to respond to
fludrocortisone
Obstructive uropathy
Sickle cell anemia
Lupus
Triameterene (Bactrim)
Amiloride
Lets do some cases
25 year old man
CC: Recurrent kidney stones
serum urine

137 112 14 55 73
3.5 17 1.2 23
urine pH 6.5

Type 1 classical distal RTA

36 yr old. Diabetes since age 12,
retino-pathy, neuropathy. On insulin
and ACEi
142 112 32
6.0 20 1.9
urine pH 5.5
Type 4 RTA
What do you do?
45 year old with alcohol abuse.
Also c/o occasional diarrhea.
132 107 10
3.2 17 0.6
Albumin 2.9
7.44 / 28 / 96 / 19
36 yr old. Diabetes since age 12,
retino-pathy, neuropathy. On insulin
but not an ACEi
142 112 32 132 98 600 54
4.7 23 1.9 6.2 10 2.6
135 115 36
urine pH 5.5 300
4.8 14 2.0
7.31 / 30 / 115 / 15
22 y.o. AA female with hyperkalemia
and microscopic hematuria
Urinalysis
140 115 18 1.015
pH 6.5
6.0 18 1.2
+ Blood
+ WBC
20-50 RBC
Systemic Lupus Erethematosus 1 RBC cast
Electrogenic Distal RTA
AE
• 66 yo white male
• PMHx DM, paraplegia 2° MVA
• Klebsiella urosepsis induced ARF
• Blood Cxrs + for Klebsiella
8/16 31 8/29
139 107 139 111 56
5.4 20 • 3.9 14 gtt
Start bicarbonate
1.2 2.8
8/26 38 8/30 62
138 104 137 104
4.4 21 3.5 22
1.9 3.0
8/28 53
137 108 7.52 / 58 / 31 / 25
• 3.8oral bicarbonate
Start 16 Respiratory alkalosis
2.9