some variations in the acid-base balance of the blood … · abnormal variations in the acid-base...

SOME VARIATIONS IN THE ACID-BASE BALANCE OF THE BLOOD IN DISEASE.*

BY VICTOR C. MYERS AND LELA E. BOOHER.

(From the Department of Biochemistry, New York Post-Graduate Medical School and Hospital, New York.)

(Received for publication January 31, 1924.)

In 1917 Van Slyke and Cullen’ described a relatively simple method of measuring the so called “alkaline reserve” of the body by estimating the plasma bicarbonate. This method quickly found extensive application in the study of pathological conditions. Van Slyke and Cullen recognized at the time that the plasma bicarbonate would serve as an adequate index of acidosis or alkalosis only as long as these conditions remained compensated, i.e. the Cn remained normal, but it was, believed then that the Cn was a physiological constant and did not change appreciably until shortly before death. Subsequent studies by a number of differ- ent investigators showed, however, that uncompensated conditions do occur, not only in disease but also in normal individuals as a result of altered pulmonary ventilation or exercise. Van Slykez was the first to correlate the factors involved in the normal and abnormal variations in the acid-base balance of the blood. He pointed out that there were nine theoretically possible variations, depending on the fact that the blood bicarbonate might be high, low, or normal, and in each of these conditions the pH might be high, low, or normal. As thus classified, only one condition can be considered as normal, that in which both the blood bicarbonate and pH are within normal limits.

* A report of these observations was presented at the St. Louis meeting of the American Society of Biological Chemists, December, 1923, see J. Biol. Chem., 1924, lix, p. xxiii.

i Van Slyke, D. D., and Cullen, G. E., J. Biol. Chem., 1917, xxx, 317. 2 Van Slyke, D. D., J. Biol. Chem., 1921, xlviii, 153.

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700 Acid-Base Balance of Blood in Disease

Since the publication of this summary of the acid-base variations of the blood by Van Slyke in 1921, a number of investigations have been reported which have extended our knowledge of these variations. Increasing attention has been given to the study of the acid-base equilibrium of the blood and the literature on this subject has now become quite extensive. Two very excellent reviews of our present information of the acid-base equilibrium of the body have recently been published by Wilson3 and by The Haemoglobin Committee.4 We shall, therefore, refer only to the literat,ure which is specifically connected with our present problem and make such references as may be indicated by the particular subject under discussion.

Although many conditions of abnormal acid-base balance have been reported, there has been little effort directed toward a corre- lation of these varying conditions into a comprehensive survey, with a uniform method of analysis. It was hoped that by such a study an abnormal acid-base balance would be disclosed in conditions where it had hitherto been unrecognized and further that the limitations of the adequacy of the bicarbonate determination might be more accurately defined.

As a measure of the acid-base balance of the blood we have est.imatcd the pH and COz content of the blood plasma. In a recent paper we have described5 a simple microcolorimetric tech- nique of estimating the hydrogen ion concentration of blood plasma, based upon an adaptation of the calorimetric method of Cullen to the Myers’ bicolorimeter. This method has been employed for the estimation of the pH, while the method of Van Slyke (Van Slyke and Cullen,’ Van Slyke,’ and Van Slyke and Stadies) has been used for the bicarbonate estimation.

The blood for each analysis was collected under oil and trans- ferred to a specially constructed 5 cc. bulb tube and kept entirely out of contact with air throughout the manipulation. The plasma

3 Wilson, D. R., Physiol. Rev., 1923, iii, 295. 4 The Haemoglobin Committee of the Medical Research Council, Special

Rep. Series 72, The acid-base equilibrium of the blood, London, 1923. 5 Myers, V. C., Schmitz, H. W., and Booher, L. E., J. Biol. Chem., 1923,

Ivii, 209. 6 Cullen, G. E., J. Biol. Chem., 1922, lii, 501. 7 Van Slyke, D. D., J. Biol. Chem., 1917, xxx, 347. * Van Slyke, D. D., and S&die, W. C., J. Biol. Chem., 1921, xlix, 1.


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V. C. Myers and L. E. Booher 701

separated from this amount of blood was sufficient for the estimation of pH, COZ content, and in many instances, the CO2 capacity. The pH was estimated within 15 minutes after the blood specimen had been collected. Inasmuch as the difference between COZ content and COZ capacity depends on the CO2 ten- sion of the blood at the time of its separation from the cells, the CO2 capacity has seemed to us to add little information that could not be found from the estimation of the COZ content alone. While there may be some criticism of our method from the standpointof accurate constants for the calculation of the pH and further refinement of this mathematical consideration may vary the absolute figures slightly, this will not invalidate our findings.

In our experience the pH of venous blood plasma of normal individuals at rest and at sea level falls between pH 7.35 and 7.43 and we are inclined to regard figures below 7.32 and above 7.47 as definitely abnormal. Our data, collected from a study of over 200 cases at the Post-Graduate Hospital, support the conception advanced by Van Slyke, and we have encountered conditions of acid-base variation which fall into each of the. nine areas described by him. Our data also indicate that an abnormal acid- base balance is more frequently encountered than has heretofore been supposed and that there is a very practical importance in recognizing these conditions.

DISCUSSION.

In order to simplify the report of our investigation and to present the data systematically, we have classified our findings according to the nine areas outlined by Van Slyke. The data are given in Table I, the cases being arranged according to areas, from Area 1 to 9. Where the data on a given case shift from one area to another, they have all been given together in the area under which the case is discussed.

Area 1, characterized by a high pH and a high plasma bicarbonate, has been encountered after the administration of NaHC03 in large quantities, following x-ray treatment, as a result of loss of HCl through persistent vomiting, and from our limited experience it would seem that this condition might be associated with certain gall bladder conditions. The ratio of BHC03:H&03


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TABL

E it.

Data

Sh

owing

Ab

norm

al

Varia

tions

in

th

e Ac

id-B

ase

Bala

nce

of th

e Bl

ood.

Plasm

a co

*.

“%!I:

NW

le. Ag

e. SE

X. Da

te.

PlS9II

la pH

at 3

8”.

COIlI-

Di

agno

sis,

rem

arks

. Co

ntent.

bin

ing

POW

W.

1 N

. M

.

yrs.

52

2 F.

H.

41

3 G

. B.

45

4 M

. S.

61

B. W

. 52

L.

c.

62

M.

L.

12

M.

L.

52

.-

F F.

M.

M.

F.

F.

I‘ M.

-

19ss

-a4

vol.

per

cent

Apr.

9 “

9 7.

52

83

“ 10

7.

45

79

May

3

7.49

76

July

3

7.40

“

26

7.49

“

29

7.50

O

ct.

29

7.53

“

31

7.53

N

ov.

2 7.

52

“ 21

7.

56

“ 22

7.

57

Dec

. 5

7.60

“

3 7.

52

“ 17

7.

52

“ 17

7.

53

“ 21

7.

40

75

66

70

70

56

62

75

67

70

63

58

-

- : 1

-

Area

1.

vol.

oer

cent

98

87

79

Cho

lecy

stec

tom

y,

NaHC

Os

40

gm.,

frequ

ent

vom

iting

. Ur

ea

N 2

2 m

g.

Seco

nd

anal

ysis

on

Apr

. 9,

6 h

rs.

afte

r fir

st.

Cho

lecy

stec

tom

y,

NaHC

Oa,

fre

quen

t vo

miti

ng,

tem

pera

- tu

re

102.

4”F.

G

astri

c ul

cer;

Sipp

y tre

atm

ent.

68

70

Duod

enal

ul

cer;

Sipp

y tre

atm

ent,

disc

ontin

ued

Oct

. 31

.

59

Urea

N

10

mg.

68

76

Ca

of s

tom

ach,

x-

ray

ther

apy,

Na

HCO

s,

vom

iting

. Ur

ea

N

14 m

g.

Diab

etes

, sm

all

amou

nt

of a

lkali

give

n.

Acid

osis

diag

nose

d on

adm

issio

n,

pers

isten

t vo

mit,

ing,

on

e do

se N

aHCO

a.

Bloo

d ch

lorid

es

0.43

8 pe

r ce

nt.

Chro

nic

neph

ritis,

fre

quen

t vo

miti

ng,

NaHC

Oe,

ur

ea

N

73 m

g.,

alka

li di

scon

tinue

d D

ec.

18.


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9 D

. hl

. 37

M

. 10

A.

c.

56

F.

11

F. G

. 52

M

.

12

M.

K.

13

S. B

. 14

I.

H.

15

J. G

. 16

S.

,L.

17

G.

B.

18

J. S

. 19

D

. M

. 20

L.

c.

21

L. I

. 22

B.

A.

23

J. D

. 24

13

. A.

25

J. L

. 26

H

. S.

35

M. .

Jan.

12

7.

56

“ 17

7.

58

(‘ 22

7.

54

“ 28

7.

47

“ 24

7.

54

“ 26

67

58

88

65

F.

43

M.

57

“ 57

F.

45 9 19

26

30

34

30

28

29

M. “ F.

M. “ “ “ “ “ ‘I

May

10

7.

47

“ 10

7.

47

(‘ 7

7.49

N

ov.

26

7.51

“

26

7.51

D

ec.

6 7.

47

July

3

7.40

Ap

r. 13

7.

41

July

8

7.43

“

4 7.

34

Nov

. 22

7.

38

“ 19

7.

43

“ 19

7.

41

“ 15

7.

41

Oct

. 19

7.

39

Dec

. 20

7.

45

- -

84

83

88

104

Hepa

tic

absc

ess,

pos

tope

rativ

e,

tem

pera

ture

10

2.2”

F.

Gas

troen

tero

stom

y,

tem

pera

ture

10

1.8”

F.

Ca

of

stom

ach,

pe

rsist

ent

vom

iting

. O

pera

ted

Jan.

25

. Bl

ood

chlo

rides

0.

413

per

cent

. In

test

inal

ob

stru

ctio

n,

pers

isten

t vo

miti

ng,

blood

ch

lorid

es

0.32

0 pe

r ce

nt,

teta

ny.

c

75

63

66

69

72

66

66

66

71

64

Area

s 2

and

3.

Frac

ture

, fe

ver

101°

F.

Syph

ilis,

reac

tion

to a

rsph

enam

ine,

fe

ver

102°

F.

61

Diab

etes

, fe

ver.

66

“ wi

th

gang

rene

, te

mpe

ratu

re

102“

F.

66

Feve

r 10

2°F.

“

100.

8”F.

Area

4.

.Y

67

69

69

70

69

Gas

tric

ulce

r; Si

ppy

treat

men

t. Ch

orea

. Ac

ute

rheu

mat

ic fe

ver,

tem

pera

ture

10

1°F.

Ep

ileps

y.

Duod

enal

ul

cer;

Sipp

y tre

atm

ent.

“ ‘I

‘I “

‘I “

“ ‘I

“ “

2nd

day

terti

ary

phos

phat

es.

Gas

tric

ulce

r, al

kali

befo

re

adm

issio

n.

Hodg

kin’s

dise

ase,

af

ter

radi

um

treat

men

t.


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TABL

E I-C

ontin

ued.

2

Plas

ma C

O%

%LF

Na

XXV3

Ag

e. SC

-C.

Date.

Pla

sma

pH

at 38

”. CO

IYP

Diag

nosis

, re

mar

ks.

Conte

nt.

bining

PO

IVW

.

T

27

S.

G.

28

R.

S.

49

29

W.

T.

35

30

E.

S.

73

31

G:

P.

25

32

M.

B.

33

E.

H.

34

A.

W.

35

E.

C.

36

c.

w.

37

F .P

. 38

S.

K.

39

H.

B.

40

H.

B.

41

A.

M.

42

S.

67

50

51

39

31

46

65

14

53

Mar.

28

7.34

Ap

r. 18

7.

36

(‘ 25

7.

41

“ 27

7.

34

May

15

7.40

“

22

7.37

“

29

7.36

Ju

ne

13

7.36

Ju

ly 3

7.36

“

4 7.

44

I‘ 4

7.36

Se

pt.

8 7.

40

“ 10

7.

37

Oct.

22

7.39

No

v. 12

7.

38

Jan.

14

7.

42

“ 15

7.

42

“ 19

7.

42

I- vo

l. pe

r cm

t

47

47

46

41

37

49

42

49

29

41

49

33

37

37

53

49

49

Area

6.

I vo

l. ,e

r ce

nt

28

w -

$z

CD

Diab

etes

, 4

hrs.

afte

r in

sulin

. “

insu

lin

treat

men

t. “

Chro

nic

neph

ritis,

ur

ea

N 46

m

g.

Ca

of

pros

tate

. Di

abet

es.

“ “ an

d pu

lmon

ary

tube

rcul

osis.

‘<

blo

od

suga

r 0.

139

per

cent

.. I‘

insu

lin

and

NaHC

OS.

Myo

card

ial

insu

fficie

ncy.

Ne

phrit

is,

urea

N

GO m

g.

‘I “

IL 1

05

“ I‘

“ ”

61

“ Ur

emia

“ “

93

“ Ne

phrit

is “

“ 28

“

Card

ioren

al di

seas

e.

Card

iac

deco

mpe

nsat

ion.

44

49

34

43

50

37

42

43


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43

44

E. L

. 47

F.

E.

L.

I I

F.

47

50

W.

H.

50

M.

W.

H.

I I

M.

45

46

47

48

C.

G.

C.

G.

M.

M.

c.

c.

C.

C.

23

“ 23

‘<

P.

P.

48

48

“ “

L. A

. L.

A.

66

“ 66

‘I

49

S. G

. 22

50

J.

B.

6 51

R

. M

. 45

52

W

. T.

35

53

M.

R.

58

54

D.

D.

32

55

T.

G.

28

M.

M. “ “ F.

M. “

Apr.

20

7.30

“

23

7.40

M

ay

8 7.

28

‘I 9

7.28

“

14

7.30

“

21

7.35

Ju

ne

8 7.

31

“ 9

7.33

“

11

7.33

‘I

13

7.33

Mar

. 28

7.

24

“ 28

7.

34

“ 29

7.

29

Apr.

18

7.36

M

ar.

30

7.22

Ap

r. 5

7.15

“

17

7.32

“

27

7.34

“

27

7.22

“

19

7.27

“

24

7.16

“

30

7.22

M

ay

4 7.

28

(‘ 11

7.

27

“ 19

7.

28

Area

s 7

and

8.

63

Card

iac

deco

mpe

nsat

ion.

63

“

“ im

prov

ed.

62

Pros

tatic

hy

pertr

ophy

. 57

“

I‘ 56

“

“

58

‘I ‘I

;c

57

62

Diab

etes

, af

ter

alka

li.

63

63

58

57

62

62

Chro

nic

tube

rcul

osis,

au

ricul

ar

fibril

latio

n.

g s2

Area

9.

22

28

30

21

20

Diab

etes

, blo

od

suga

r 0.

233

per

cent

. ‘I

4 hr

s.

afte

r in

sulin

. “

afte

r in

sulin

in

ject

ion.

“

insu

lin

treat

men

t. “ “

died

few

hr

s.

late

r. Ch

roni

c ne

phrit

is,

card

iac,

hy

perte

nsio

n.

“ “

I‘ I‘

Ca o

f br

east

, m

etas

tasi

s in

lu

ng.

Diab

etes

. Ch

roni

c ne

phrit

is,

urea

N

135

mg.

‘I

“ “

“ ur

ea

N

111

mg.

“

“ ‘I

‘L

gg

“ “

“ “

“ 13

2 “

Died

M

ay

19.

47

40

46

47

33

22

25

35

46

26


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% f

NaIW

3. Ag

e. St

%

Date.

56

S.

B.

yrs .

73

57

E.

F.

60

58

M.

I. 37

59

J.

C.

28

60

M.

H.

50

61

T.

M.

62

L.

L.

63

H.

B.

64

J.

B.

52

65

37

M.

F.

M.

M.

F.

M. “ F.

M.

19.38

-84

May

8 7.

15

“ 18

7.

25

‘( 25

7.

22

“ 28

7.

16

“ 30

7.

18

June

1

7.06

“

2 7.

05

May

24

7.31

Ju

ne

4 7.

17

“ 6

7.08

“

8 6.

98

“ 9

7.01

“

5 7.

13

“ 6

7.28

”

8 7.

31

July

4 7.

26

LL

8 7.

30

act.

18

7.14

“

19

7.32

“

26

7.30

Ja

n.

21

7.30

TABL

E I-C

onclu

ded.

Plasm

a CO

%

Pla.R

Tlla

pH

at 38

”. CO

IIP

Diag

imsis

, re

mar

ks.

Conte

nt.

bining

po

wer.

,

- -

Area

9-

Cont

inued

. -

sol.

%r

cent

19

20

19

21

17

13 6 4 11

10

38

57

27

32

12

36

35

42

vol.

per

cen.1

25

20

12

20

13

62

29

38

16

36

Chro

nic

neph

ritis,

ur

ea

N 89

m

g.

“ ‘I

“ ‘I

urea

N

86

mg.

“

“ ‘I

“ 10

9 “

‘I ‘I

I‘ “

“ “

Died

Ju

ne

2.

Diab

etes

. Ca

of

kid

ney.

“ L‘

‘I

‘I I‘

“ ur

ea

N 12

0 m

g.

“ LC

“

alka

li giv

en.

Died

Ju

ne

9.

Diab

etic

com

a.

Diab

etes

(a

fter

insu

lin).

“ (

“ alk

ali).

Neph

ritis,

ur

ea

N 53

m

g.

“ re

ceive

d al

kali.

‘I ur

ea

N 10

7 m

g.

Neph

rosis

. Ur

emia.

Ne

phrit

is,

urea

N

83

mg.

-


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is altered by an increase of BHCOS. The highest pH we have encountered pathologically was 7.60, occurring in a case of diabetes following NaHC03 administration. The CO2 content of this plasma was 75. It is of interest to note that acetone was being excreted by the kidneys at this time. It seems to us to be theoretically possible that the production of acetone may be increased as a result of increased alkalinity of the blood. It is well known that a decreased hydrogen ion concentration of the blood decreases the conversion of oxyhemoglobin to hemoglobin. If this is sufficiently marked, the result is oxygen want in the tissues and consequently greater inability of the cells to oxidize fats nor- mally.

We are unable to explain at this time the remarkable change in blood reaction following x-ray treatment. Husseyg has observed a condition of uncompensated alkali excess in rabbits following x-ray exposure, an observation which we have confirmed. It should perhaps be noted that there was some vomiting in the case in question, but this was neither severe nor persistent.

In three instances a condition of uncompensated alkalosis re- sulted primarily from persistent vomiting. The pH- values were 7.52, 7.54, and 7.54, associated with plasma COz contents of 70, 88, and 83, respectively. The whole blood chlorides found simul- taneously in these cases were 0.438, 0.320, and 0.413 per cent, respectively.

With NaHC03 therapy, we have found that the bicarbonate value invariably rises before the pH becomes abnormal. We have further observed that after the administration of NaHC03 has been discontinued the pH sometimes returns to normal in advance of the COz value while in other instances the reverse is true.

While persistent vomiting was the actual cause of the alkalosis in several instances, emesis frequently occurred in other cases after the alkalosis had become established. Some, but not all, cases in Area 1 showed an increase of body temperature.

Areas 2 and 3 are characterized by an abnormally high pH and a normal or low COZ content. Cases of overventilation as a result of fever are included in these areas, the rapid loss of HzC03 being the responsible factor in changing the BHC03:HzC03 ratio from

s Hussey, R. G., J. Gen. Physiol., 1921-22, iv, 511.


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its normal balance. In fevers the increase in elimation of H&J03 need be only relatively small to affect this ratio. Koehler’O reported this condition in cases of fever and pointed out its similarity to the overventilation due to the immersion of individuals in warm water. Voluntary overventilation for a short period of time is said to cause a greater degree of alkalosis than has ever been reported as a condition of pathological occurrence.

The highest CO2 we have found associated with a high pH was 88. This figure for CO2 capacity increased to 104 shortly before death. The lowest CO2 found associated with a high pH was 50.

We are inclined to think that alkalosis is a condition often over- looked and sometimes confused with acidosis by the clinician. We believe that a great deal of care should be exercised in the administration of alkali. In cases with impairment of renal function the administration of alkali is a dangerous procedure, unless it is accompanied by estimations of the blood bicarbonate. Inone instance, a case of nephritis, a small amount of alkali was sufficient to produce an uncompensated alkalosis, accompanied by a great deal of discomfort for the patient. 3 days after the alkali therapy had been discontinued the acid-base balance returned to normal and t,he patient was markedly improved clinically.

Area 4 is characterized by a normal pH and a high plasma bicarbonate. This condition has been encountered after the administration of NaHC03 in moderate amounts over a considerable period of time. It has also been observed in cases of gastric ulcer during Sippy treatment. We have likewise followed the acid-base balance of the blood of patients with gastric ulcer receiving tertiary phosphates for the neutralization of the free HCl of the stom- ach. Inasmuch as these phosphates are probably not absorbed from the alimentary tract, the administration of tertiary phosphates functions only in the neutralization of free HCl of the gastric juice and does not increase the systemic alkali. In our experience,ll at least, the effect of administering tertiary phosphates in moderate amounts, over a considerable period of time to patients suffering from gastric ulcer, did not result in any definite change in the acid-base balance of the blood. In one case a bicar-

10 Koehler, A. E., Arch. Int. Med., 1923, xxxi, 590. I1 Shattuck, H. F., Rohdenburg, E. L., and Booher, L. E., J. Am. Med.

Assn., 1924, lxxxii, 200.


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bonate content of 75 was found associated with a normal pH, after NaHC03 administration. We have observed that the change from normal acid-base balance to the condition of uncompensated alkalosis of Area 1 as the result of administration of NaHC03 proceeds by Area 4 and returns by the same area or by Area 2. The buffering action of the blood and the extent to which H&OS can be retained to balance the increase of BHCOs probably determines its capacity to remain compensated.

Area 5 is the area of normal acid-base balance and needs little discussion, except to mention that in our experience the pH of normal individuals falls between 7.35 and 7.43. We are inclined to regard figures below 7.32 and above 7.47 as definitely abnormal. Our values for the bicarbonate content of the plasma in this area range from 55 to 65. It has seemed unnecessary to include our data falling in the normal Area 5.

Area 6 is a condition of compensated alkali or CO2 deficit, the pH being normal and the COz low. This area includes those cases termed compensated a,cidosis. This condition has been found in cases of diabetes in which the abnormal acid production is not suffXently rapid to overtax the compensating powers of the organism. Here there is an increased formation of ammonia by the kidney to combine with the acids excreted and the urine becomes more acid. As the fixed acids displace the HCOs of the blood bicarbonate, the COZ -carrying capacity of the blood is decreased so that t’here is need of more rapid ventilation to rid the body of the CO2 formed constantly. Outside of the buffering action of the proteins and phosphates of the blood, the extent of the chloride shift and the amount of hemoglobin present would seem to deter- mine the possible degree of compensation. The lowest COz content we have observed associated with a normal pH was 33, occurring in a case of diabetes after insulin and NaHC03 administration. Early cases of nephritis also fall into this area but soon shift to Area 9 when the elimination of acid radicles is seriously impaired.

Areas 7 and 8 are conditions of uncompensated COZ excess, characterized by a low pH and a high or normal COZ. We have found this condition of acid-base balance in cases of cardiac decompensation, impaired ventilation in the lungs, and chronic tuberculosis complicated with auricular fibrillation. This con-


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dition seems to be encountered only occasionally. The change in the BHC03:H2COe ratio is due to an accumulation of H&OS in the blood. The lowest pH we have encountered in Areas 7 and 8 was 7.28, the highest CO2 content 63, and the lowest COZ content 56. In the one case of cardiac decompensation the pH returned to normal with improvement of the cardiac condition while the CO2 content remained constant.

Area 9 is a condition of uncompensated acidosis, and is characterized by a low pH and a low plasma bicarbonate. This condition results from the formation of abnormal acids beyond the power of the organism to compensate, as a result of impaired renal function to eliminate normal acids or the impaired function of the kidney to form ammonia. The first group was encountered in cases of diabetes, where P-hydroxybutyric and acetoacetic acids are formed in excess of the ability of the body to compensate by buffer action or in excess of the ability of the kidney to eliminate them with sufficient rapidity as acids or neutralized salts. As a result the BHCOs is attacked by the fixed acids, which displace the -- HC03 of the BHC03. The rate of breathing is increased due to the decreased efficiency of the blood as a carrier of COZ. Cullen and Jonas12 have recently reported observations on the influence of insulin on the acid-base balance of diabetic acidosis. They found that t.he plasma pH and bicarbonate returned to normal coincidently. Our data, although somewhat more limited, seem to support this general conclusion. It is of interest to note that in some of the same cases which we have studied, Killian13 has found that the rise in the plasma bicarbonate, following insulin therapy, was accompanied by an almost simultaneous drop in the acetone content of the blood and in its urinary excretion. The lowest pH encountered in cases of diabetes during this investigation was 7.13, and this was associated with a plasma bicarbonate content of 10 volumes per cent.

The other group of cases given in Area 9 (see Table I) all suffered from impaired renal function. Here there is a retention of acid radicles which are eliminated by the normal kidney. It is inter- esting to note that two of the nephritics lived for many days in a

I2 Cullen, G. E., and Jonas, L., J. Biol. Chem., 1923, Ivii, 541. I3 Killian, J. A., Proc. Sot. Exp. Biol. and Med., 1923-24, xxi, 22.


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condition of uncompensated acidosis, and in one of these the pH remained at a low level throughout.

The lowest pH we have encountered in any condition was 6.98, with a COz content of 4, and a COz capacity of 12. This observation was made on the blood of a patient suffering from carcinoma of the kidney. , We have encountered many cases with pH values from 7.25 to 7.05

In the few cases of carcinoma which we have had the oppor- tunity of examining (11 cases), the pH fell within normal limits, ,except where there were other complications. This does not support the findings of Chambers,14 who found that the dialysate of the venous blood of carcinoma cases was distinctly more .alkaline than that of his normal subjects.

SUMMARY.

With the method employed the pH of the venous blood plasma of normal individuals at rest and at sea level was found to fall between 7.35 and 7.43, and figures below 7.32 and above 7.47 can probably be regarded as definitely abnormal.

Venous blood plasma may possess a normal CO2 content, while the pH is outside the probable normal limits. Normal values for the CO2 content have been found with pH values as high as 7.51 and as low as 7.28. Likewise the pH of the blood plasma may be normal, although its COz content falls outside the probable normal limits. Values for the CO2 as high as 75 and as low as 33 have been found in association with a normal pH. Therefore, the plasma bicarbonate alone does not constitute an adequate index of the acid-base balance. However, in those cases of abnormal balance due to alkali deficit, which after all constitute much the largest clinical group, the bicarbonate appears to be ,entirely adequate so long as the values do not fall below 35.

Uncompensated alkalosis does not appear to be a rare condition. It has been encountered following the administration of sodium bicarbonate, following x-ray treatment, after prolonged periods of persistent vomiting, in the course of fevers, and possibly in gall bladder disease.

I4 Chambers, W. H., J. Biol. Chem., 1923, Iv, 229.


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The uncompensated acidosis of severe diabetes promptly responds to the administration of insulin, as indicated by the rise in plasma pH and bicarbonate.

Contrary to the opinion formerly held, patients may live for a comparatively long period with low pH values.

The data reported are in harmony with the conception of the variations in the acid-base balance of the blood advanced by Van Slyke.


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Victor C. Myers and Lela E. BooherIN DISEASE

ACID-BASE BALANCE OF THE BLOOD SOME VARIATIONS IN THE

1924, 59:699-712.J. Biol. Chem.

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