Homeostasis of internal enviroment

Homeostasis of internal enviroment

Disorders of the acid-base chemistry, influence of respiration, lungs and

altered metabolism

1865 Claude Bernard

External environment of organism

Internal environment of the cells

1865 Claude Bernard


External environment of cells= internal environment

Their properties must enable optimal functioning of cellular structures

i.e. temperature, volume, osmolarity, pH, ionic composition, O2, CO2 concentrations, concentration of glucose etc.

THEY ARE STAEDY AND INDEPENDENT ON FLOATING CONDITIONS OF EXTERNAL

ENVIRONMENT AND ON VARIED LEVELS OF CELLULAR

METABOLIC ACTIVITY

1932 Walter Cannon


External environment of cells = internal environment




ENVIRONMENT AND ON VARIED LEVELS OF

CELLULAR METABOLIC ACTIVITY

Homeostasis - the ability or tendency of an organism or cell to maintain internal equilibrium by adjusting its physiological processes.

1932 Walter Cannon nearly „cybernetic“ definition in

1932

Homeostatic system is able to maintain its essential variables within limits acceptable to its own structure in the face of unexpected disturbances.Homeostasis = dynamic self-regulation

1932 Walter Cannon

Arturo Rosenblueth(disciple of W. Cannon)

nearly „cybernetic“ definition in 1932


1932 Walter Cannon

Arturo Rosenblueth Nobert Wiener

collaboration



(disciple of W. Cannon)

1932 Walter Cannon

Arturo Rosenblueth(žák W. Cannona)

Nobert Wiener

1948: N. Wiener: Cybernetics or Control and Communication in the Animal and the Machine

collaboration



1932 Walter Cannon






ENVIRONMENT AND ON VARIED LEVELS OF

CELLULAR METABOLIC ACTIVITY


extracellular fluid

1932 Walter Cannon

intracellularfluid





extracellular fluid

1932 Walter Cannon

intracellularfluid





Metabolism

extracellular fluid

1932 Walter Cannon

intracellularfluid





Metabolism

Outputs

Inputs

StorageBalance between input and output flow

depletion

retention?

?

extracellular fluid - ECF

intracellular fluid - ICF

Metabolism

ConcentrationsBalance estimation


plasma

interstitial fluid - ISF


Metabolism

Concentrations

extracellular fluid -ECF

capillaries

Lymph


Balance estimation

intravascularfluid


Metabolism

plasma blood cells(part of ICF)


capillaries capillaries

Lymph



intravascularfluid


Metabolism

plasma

capillaries

transcellular fluid

extracellular fluid -ECFcapillaries

Lymph


blood cells(part of ICF)


intravascularfluid


Metabolism

plasma

capillaries

Lymph


LungsGIT

Kidney

„exc

hang

ers“


interstitial fluid - ISF transcellular fluid


intravascularfluid


Metabolism

plasma

capillaries

Lymph


LungsGIT

Kidney

„exc

hang

ers“

Circulation„mixing“




intravascularfluid


Metabolism

plasma

capillaries

Lymph


LungsGIT

Kidney

„exc

hang

ers“





intravascularfluid


Metabolism

plasma

capillaries

Lymph


LungsGIT

Kidney

„exc

hang

ers“





CO2 H +

ACID-BASE BALANCE

+

H+

OH-

H2O

H2O

H2O OH-

H3O+

+

-

-

H2O

OH-

H+

H2O

H2O OH-

H3O+

H+

OH-

H2O H2O

H2O

pH= -log [H+]

H+

OH-

H2O

OH- H+ +H2O

v1=k1[H2O]

v2=k2[H+][OH-]

v1=v2

k1[H2O] =k2[H+][OH-]

k2

[H+][OH-][H2O]

k1K‘ = =

[H2O] = constant

K‘ [H2O] = [H+][OH-]

Kw = [H+][OH-] = 2,4 10-14 mol2/l2 at 37°C

[H+] = 1,55 10-7 mol/l ´= 155 nmol/l

[OH-] = 1,55 10-7 mol/l ´= 155 nmol/l

pH = 7.4[H+] = 10-7,4 mol/l

´= 40 nmol/l

OH-

H3O+

pH= -log [H+]

H+

OH-

H2O

OH- H+ +H2O

v1=k1[H2O]

v2=k2[H+][OH-]

v1=v2

k1[H2O] =k2[H+][OH-]

k2

[H+][OH-][H2O]

k1K‘ = =

[H2O] = constant

K‘ [H2O] = [H+][OH-]

Kw = [H+][OH-] = 2,4 10-14 mol2/l2 at 37°C

[H+] = 1,55 10-7 mol/l ´= 155 nmol/l

[OH-] = 1,55 10-7 mol/l ´= 155 nmol/l

pH = 7.4[H+] = 10-7,4 mol/l

´= 40 nmol/l

OH-

H3O+

H2O

H2O

H2O

H2O

H2O H2O

H2O

H2O

H2O

H2O

H2O

H2O

H2O

H2O

H2O

H2O

H2O H2O

H2O

H2O

H2O

H2O

OH-

H3O+

H2O

H2O

H2O

H2O

H2O H2O

H2O

H2O

H2O

H2O

H3O+

OH-

H2O

H2O

H2O

H2O

H2O H2O

H2O

H2O

H2O H3O+

OH-

H2O

H2O

H2O

H2O

H2O

H2O H2O

H2O

H2O

H2O H3O+

OH-

H2O

H3O+ + H2O

H3O+

H2O

H2O H2O

H2O

H2O

H2O

H2O

H2O

H2O

H2O H2O

H2O

H2O H2O

H2O

OH-

H2O + H3O+

OH- + H2O H2O + OH-

H3O+ + H2O

H2O

H2O H2O

H2O

H2O

H2O

H2O

H2O H2O

H2O H2O

H2O

H2O H2O

H2O

OH-

H2O + H3O+

OH- + H2O H2O + OH-

H3O+

H3O+ + H2O

H2O

H2O

H2O

H2O

H2O

H2O

H2O

H2O + H3O+

OH- + H2O H2O + OH-

H3O+

H2O H2O

H2O H2O

H2O

H2O H2O

H2O

OH-

H3O+ + H2O

H2O

H2O

H2O H2O

H2O

H2O

H2O

H2O + H3O+

OH- + H2O H2O + OH-

H3O+

H2O

H2O H2O

H2O

H2O

H2O H2O

H2O

OH-

H3O+ + H2O

H2O

H2O

H2O

H2O H2O

H2O

H2O

H2O + H3O+

OH- + H2O H2O + OH-

H3O+

H2O

H2O H2O

H2O

H2O

H2O H2O

H2O

OH-

H3O+ + H2O

H2O

H2O

H2O

H2O

H2O H2O

H2O

H2O + H3O+

OH- + H2O H2O + OH-

H3O+

H2O

H2O

H2O H2O

H2O

H2O H2O

H2O

OH-

H3O+ + H2O

H2O

H2O

H2O

H2O

H2O

H2O H2O

H2O + H3O+

OH- + H2O H2O + OH-

H3O+

H2O

H2O

H2O H2O

H2O

H2O H2O

H2O

OH-

H3O+ + H2O

H2O

H2O

H2O

H2O

H2O

H2O

H2O

H2O + H3O+

OH- + H2O H2O + OH-

H3O+

H2O

H2O

H2O

H2O H2O

H2O H2O

H2O

OH-

Break

ink

links

by bin

ding H

+

Break

ink

links

by bin

ding H

+

H+

H+

Breaking links by binding OH -

Breaking links by binding OH -

OH-

OH-

Buffer curvepH

Addition of H+ mmol/lAddition of OH- mmol/l

-7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 5 6 7

H+ + OH- H2O

H20OH-

H+

H+

OH-

H+

Cl-

Buffer curvepH


-7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 5 6 7

H+ + OH- H2O

H20OH-

H+

OH- OH-

H+

Na+

Buffer curvepH


-7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 5 6 7

H+ + Buf HBuf

H+ + Buf HBuf

HBufBuf-

H+

OH-

H2O H+

H+

Buf -

HBuf

Dilution in buffers

[H+]=K1 [Hbuf]/[Buf-]


H+

Buf -

HBuf

Dilution in buffers


no changed value

pH


H+

Buf -

HBuf

Dilution in buffers


no changed value

no changed value !


CO2

H2O

H2CO3

HCO3

-

H+

A-

TA+NH4

+

20 000 mmol/24 hod 60 mmol/24 hod

60 mmol/24 h

Practically complete reabsorbtion of HCO3-

Metabolic production od strong acidsMetabolic production of CO2

CO2

H2O

H2CO3

HCO3

H+

-A: Closed system

1. Addition of strong acid (H+ ions)

CO2

H2O

H2CO3

HCO3

H+

-

3. Establishment of new equilibriom with increased concentrations of CO2 and H2CO3

2. Consumption of bicarbonate and added H+ ions in buffer reaction

CO2

H2O

H2CO3

HCO3

H+

-A: Open system

1. Addition of strong acid (H+ ions)

CO2

H2O

H2CO3

HCO3

H+

-

CO2

H2O

H2CO3

HCO3-

H+

24 mmol/l

40 nmol/l (pH=7,40)

TA+NH4

+

20 000 mmol/24 hod

60 mmol/24 hodMetabolic production od strong acids

Metabolic production of CO2

H2O

H2CO3

HCO3-

H+

24 mmol/l

40 nmol/l (pH=7,40)

TA+NH4

+

20 000 mmol/24 hod

60 mmol/24 hodMetabolic production od strong acids

Metabolic production of CO2

CO2

TA+NH4

+

20 000 mmol/24 hodMetabolic production of CO2

CO2

H2O

H2CO3

HCO3-

H+

24 mmol/l

60 nmol/l (pH=7,2)

+1 mmol/l

dHCO3 = + 60 nmol/l-

TA+NH4

+

20 000 mmol/24 hodMetabolic production of CO2

CO2

H2O

H2CO3

HCO3-

H+

24 mmol/l

43 nmol/l (pH=7,37)

Buf -

HBuf

+1 mmol/l

dBuf - = -1 mmol/l

dHCO3 = +1 mmol/l-

60 nmol/l (pH=7,2)

Buffering systems of the blood

H2CO

3

HCO3-H+CO2

HBufBuf-

Hb- HHb

Alb-

HAlb

HPO42- H2PO4

-

H2O

H+

H+

H+

H+

++

+

+

+

+

non-bicarbonate buffersBuf = Hb + Alb + PO4

-

Buffering reactions

H2CO

3

HCO3-

H+

CO2

HBuf

Buf-

H2O

Bicarbonate buffer

Hendersson- Hasselbalch equation:

[H+] = 24 . pCO2 / [HCO3-]

or

pH = 6.1 + log ( [HCO3-] / [H2CO3] )

= 6.1 + log ( [HCO3-] / 0.03 pCO2 )

H2CO

3

HCO3-H+CO2 H2O ++

CO2

H2O

H2CO3

HCO3-

H+

40 nmol/l (pH=7,40)

Buf -

HBuf

Buffer Base (BB)

BB = [HCO3

- ]+ [Buf

- ]

Buffer Base (BB)

BB = [HCO3

- ]+ [Buf

- ]

CO2

H2O

H2CO3

HCO3-

H+

40 nmol/l (pH=7,40)

Buf -

HBuf

Buffer Base (BB)

BB = [HCO3

- ]+ [Buf

- ]

Buffer Base (BB)

BB = [HCO3

- ]+ [Buf

- ]

dH+ = +1 mmol/l-

43 nmol/l (pH=7,37)

CO2

H2O

H2CO3

HCO3-

H+

Buf -

HBuf

Buffer Base (BB)

BB = [HCO3

- ]+ [Buf

- ]

Buffer Base (BB)

BB = [HCO3

- ]+ [Buf

- ]

dBuf -

dHCO3-

dH+ = +1 mmol/l

dBuf - + dHCO3

- = -1mmol/l

CO2

H2O

H2CO3

HCO3-

H+

24 mmol/l

40 nmol/l (pH=7,40)

Buf -

HBuf

A: Titration CO2 „in vitro“

Buffer Base (BB)

BB = [HCO3

- ]+ [Buf

- ]

Buffer Base (BB)

BB = [HCO3

- ]+ [Buf

- ]

CO2

H2O

H2CO3

HCO3-

H+

24 mmol/l

40 nmol/l (pH=7,40)

Buf -

HBuf


Buffer Base (BB)

BB = [HCO3

- ]+ [Buf

- ]

Buffer Base (BB)

BB = [HCO3

- ]+ [Buf

- ]

dHCO3 = +1 mmol/l-

dH+ = +1 mmol/l-

CO2

H2O

H2CO3

HCO3-

H+

24 mmol/l

43 nmol/l (pH=7,37)

Buf -

HBuf

+1 mmol/l

dBuf - = -1 mmol/l

dHCO3 = +1 mmol/l-


Buffer Base (BB)

BB = [HCO3

- ]+ [Buf

- ]

Buffer Base (BB)

BB = [HCO3

- ]+ [Buf

- ]

CO2

H2O

H2CO3

HCO3-

H+

+1 mmol/l = 1 000 000 nmol/l

24 mmol/l

43 nmol/l (pH=7,37)

Buf -

HBuf

+1 mmol/l

dBuf - = -1 mmol/l

dHCO3 = +1 mmol/l-


Buffer Base (BB)

BB = [HCO3

- ]+ [Buf

- ] = const

Buffer Base (BB)

BB = [HCO3

- ]+ [Buf

- ] = const

999 997 nmol/l H+

were „buffered“by nonbicarbonate

buffers

CO2

H2OH2CO3

HCO3-

H+

Buf -

HBuf

B: Titration CO2 „in vivo“

If pCO2 increases

BB = [HCO3

- ]+ [Buf

- ]

v in blood decreases

If pCO2 increases

BB = [HCO3

- ]+ [Buf

- ]


Buffer Base (BB)

BB = [HCO3

- ]+ [Buf

- ] =/= const

Buffer Base (BB)

BB = [HCO3

- ]+ [Buf

- ] =/= const

CO2

H2OH2CO3

HCO3-

H+

Buf -

HBuf

CO2

H2OH2CO3

HCO3-

H+

Diffusion by concentration gradient

B: Titration CO2 „in vivo“

HBuf

Buf -

There are small concentrations of non bicarbonate buffers in ISF

If pCO2 increases

BB = [HCO3

- ]+ [Buf

- ]


If pCO2 increases

BB = [HCO3

- ]+ [Buf

- ]


CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

Dilution – in vitro

Dilution

[H+]=K1 [Hbuf]/[Buf-]=K2[CO2]/[HCO3-]

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

Dilution



no changed value no changed value

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

Dilution


no changed value no changed value

no changed value !


CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

Dilution


no changed value changed value

changed value !

Dilution – in vivo

no changed value !

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

TA + NH4+

Buffers system acid-base disturbances:Dilutional acidemiaContractional alkalemia

CO2 balance

H+ balance

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

TA + NH4+

Buffers system acid-base disturbances:Dilutional acidemia

Dilution

CO2 balance

H+ balance

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

TA + NH4+

equilibrium shift

CO2 balance

H+ balance

Buffers system acid-base disturbances:Dilutional acidemia

Dilution

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

TA + NH4+

Hemoconcentration

CO2 balance

H+ balance

Buffers system acid-base disturbances:Contractional alkalemia

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

TA + NH4+

CO2 balance

H+ balance

Hemoconcentration


CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

TA + NH4+

equilibrium shift

CO2 balance

H+ balance

Hemoconcentration


Acid-Base equilibrium

Classical Danish approach

„Modern approach“ by Stewart and Fencl

?Siggaard-AndersenPaul Astrup



Problem: how to measure acid-base parameters in clinic

Measurement of Acid-Base parameters

pH, pCO2, [HCO3-]

HCO3-

H+

Buf-

HBuf

CO2

H2O

H2CO3


pH, pCO2, [HCO3-]

HCO3-

H+

Buf-

HBuf

CO2

H2O

H2CO3

pH, pCO2, [HCO3-]

HCO3-

H+

Buf-

HBuf

CO2

H2O

H2CO3

Alkaline reserve


pH, pCO2, [HCO3-]

HCO3-

H+

Buf-

HBuf

CO2

H2O

H2CO3

Alkaline reserve

Van Slyke 1921-22


pH, pCO2, [HCO3-]

HCO3-

H+

Buf-

HBuf

CO2

H2O

H2CO3

Alkaline reserve

Van Slyke 1921-22


.

CO2

Vacuum extraction

CO2pH, pCO2, [HCO3

-]

HCO3-

H+

Buf-

HBuf

CO2

H2O

H2CO3

Alkaline reserve

Van Slyke 1921-22


. Vacuum extraction

CO2pH, pCO2, [HCO3

-]

HCO3-

H+

Buf-

HBuf

CO2

H2O

H2CO3

Alkaline reserve

Van Slyke 1921-22


.Vacuum extraction

CO2pH, pCO2, [HCO3

-]

HCO3-

H+

Buf-

HBuf

CO2

H2O

Alkaline reserve

Van Slyke 1921-22


.Vacuum extraction

H2CO3

Pressure changes calculationn

CO2pH, pCO2, [HCO3

-]

HCO3-

H+

Buf-

HBuf

CO2

H2O

Alkaline reserve

Van Slyke 1921-22


.Vacuum extraction

H2CO3

Pressure changes calculationn

pH, pCO2, [HCO3-]

HCO3-

H+

Buf-

HBuf

CO2

H2O

H2CO3

P. Astrup 1956


Equilibration method for pCO2 measurement by Astruplog PCO

2

pH

pCO2 set

O2/CO2 gas

mixture

pH is measure

d

Titration curve

Equilibration method for pCO2 measurement by Astruplog PCO

2

pH

Titration curve

pH In blood sample before equlibration

pH after equilibration with low pCO2

Low level pCO2 In mixture

O2/CO2

pH after equilibrationwith high pCO2

High level pCO2 in mixture

O2/CO2

pCO2 in measered sample

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

Buffer Base (BB)

BB = [HCO3

- ]+ [Buf

- ]

Buffer Base (BB)

BB = [HCO3

- ]+ [Buf

- ]

depends on cHb

Normal buffer base:NBB=41.7+0.42*cHB [g/100ml]

Base Excess:BE=BB-NBB

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

+ 1 mmol H+ added to 1 litre of blood

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

1 mmol/l drop of [HCO3-] + [Buf-]

BE=-1mmol/l

+ 1 mmol H+ added to 1 litre of blood

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

+ 1 mmol OH- added to 1 litre of blood

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

1 mmol/l increase of [HCO3-] + [Buf-]

BE= 1mmol/l

+ 1 mmol OH- added to 1 litre of blood

HCO3-

H+

Buf-

HBuf

CO2

H2O

H2CO3

BB=[HCO3-] +[Buf-] = konst

Siggaard-Andersen

Siggaard-Andersen

How to measure ВВ a ВЕ?

log pCO2

pH

Plasma and blood with different hematocrit

BE=0

7.4

40 torr BE=-5

BE=-10

BE=5

BEcurve

BE=0 mEq/l

BE=-15 mEq/l

Reading of BE

Reading of BB

NBB=41,7 + 0,42 * cHBBB=BE+NBB

Measured pH

Reading of pCO2

Reading of standard bicarbonate

1962 – pCO2 electrode for direct measurement of pCO2

pH, pCO2, pO2 electrodes

pH=7.29pH=7.29

pCO2=44 mm HgpCO2=44 mm Hg

cHb=16 g/100 mlcHb=16 g/100 ml

BE=-6 mmol/l

[HCO3]=20 mmol/l

Siggaard-Andersen (1960-1962)

Definition (for blood in vitro)

- Buffer base: [BB]=[HCO3-]+[Buf-] independed on pCO2

-Normal buffer base: [NBB][BB] at pH=7.4 and pCO=40 torr and given cHb(a but in normal albumin)

- Base Excess: [BE]=[BB]-[NBB]

Defined only for standard condition not included hypo/hyperalbuminemia dilution a dehydratation original measurement for BE curve construction was provided at 38°C

Problems of Danish approach

• Problems in acute patients with abnormal hypo/hyperalbuminemia

• (if original Siggaard-Andersen nomogram is used).

Siggaard-Andersen (1974-1995)

Definition (for blood in vitro)

- Buffer base: [BB]=[HCO3-]+[Buf-] independed on pCO2

-Normal buffer base: [NBB][BB] at pH=7.4 and pCO=40 torr and given cHband given phosphate and albumin concentration

- Base Excess: [BE]=[BB]-[NBB]

Defined not only for standard condition included hypo/hyperalbuminemia dilution a dehydratation original measurement for BE curve construction was reacalculated for 37°C

Stewart teorie (1983)

Ca+ Mg+

HCO3-

Buf-

XA-

Cl-

Na+

K+

SID[H+] [OH-] = K'w[Buf-]+[HBuf] = [BufTOT]

[Buf-] [H+] = KBuf [HBuf]

[H+] [HCO3-] = M × pCO2

[H+] [CO32-] = N × [HCO3

-]

SID+ [H+]– [HCO3-] – [Buf-]– [CO3

2-]– [OH-] = 0

Peter Stewart

Stewart teory – solving equation:

[H+]4 + (SID + KBUF) [H+]3 +

+(KBUF (SID - [BufTOT])- K'w-M×pCO2)[H+]2

- (KBUF(K'w2 + M × pCO2)-N×M×pCO2)[H+]

- K'w×N×M×pCO2 = 0

pH = f (pCO2, SID, BufTOT)

Mathematical Wizardry of Steward followers

dependence of variables in the equation is identified with causality

pH = f (pCO2, SID, BufTOT)

Vladimír Fencl

H2O/Na+/Cl-/K+ balance

CO2 balance

Plasma protein balance

pCO2

SID

[BufTot]

pH

[HCO3-]

H2O/Na+/Cl-/K+ balance

CO2 balance

Plasma protein balance

pCO2

SID

[BufTot]

pH

[HCO3-]

„Modern Steward-Fencl approach“

Lungs

TISSUES

CO2

STRONG IONS

CO2

KIDNEY

STRONG IONS

GIT

STRONG IONS

Blood

Independent variables

PCO2

SID

[BufTOT]

Dependent variables

[HCO3-]

[Buf-]

[CO32-]

[OH-]

[H+] (pH)

LIVER

PROTEINS

Balance theory

HCO3-

Buf-

Buf -

BB

plasma SID = plasma BBplasma SID = plasma BB



„Modern approach“ by Stewart and Fencl

Siggaard-AndersenPaul Astrup

The same problem from different points of view?

Ca+ Mg+

HCO3-

Buf-

XA-

Cl-

Na+

K+

SID = BB

Changes SID = Changes in BB and BE

Ionic balance (Na+, K+, Cl-,…) H+ /HCO3- (strong acids) balance

The same problem from different points of view

Balance theory

LUNGD

TISSUES

CO2

Metabolic production of strong acids

CO2

KIDNEY

Extretion of TA, NH4+ (generation of HCO3

-)

GIT

H+/HCO3- loss from vomiting or

diarhea

BLOOD equlibrated with ISF

Independent variables

Respiratory balance (CO2)PCO2

Metabolic balance(H+/HCO3

-)BE, (ctH+), dSID

Buffersalbumins, phosphates,

hemoglobin

Dependent variables

[HCO3-]

[Buf-]

[CO32-]

[OH-]

[H+] (pH)

LIVER

PROTEINS

Balance theory

HCO3-

Buf-

Buf -

BB

plasma SID = plasma BBplasma SID = plasma BB

Patogenesis of acute hypoproteinemic alkalosis

Alb - H+

Liver – albumine

production

Endotel, liver – albumine

degradation

Alb - H+

Liver – albumine

production

Endotel, liver – albumine

degradation

HCO3-

H2O + CO2

HCO3-

Patogenesis of acute hypoproteinemic alkalosis

-d[Alb-] = d[HCO3-]

no changed value of SID

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

TA + NH4+

Acute hypoproteinemia

CO2 balance

H+ balance

Balance disorders: Hypoproteinemic alkalosis

HCO3-Alb - H+

+H2OCO2

production

degradation

-d[Alb-] = d[HCO3-]

no changed value of SID

CO2 metabolic production (15 000-20 000 mmol/24 h

Strong acids metabolic production (60-70 mmol/24 h



Buffer systems



Buffer systems



Buffer systems

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

TA + NH4+

CO2 balance

H+ balance1. Buffer systems (msec)2. Respiration control (12 hours)3. Kidney control (3-5 days)

Acid-base regulation

Exchange H+/K+ H+/Na+ between cells and ECFRole of liver in AB regulation

1

K+mmol/l

6,9

2

3

4

5

6

7

8

7,0 7,1 7,2 7,3 7,4 7,5 7,6 7,7 7,8 pH

normal kalemia rangeA

K+

H+ H+

K+

A: Norm

B

K+

H+ H+

K+

B: Acidemia - exchange K+ for H+

K+

C

K+

H+ H+

K+

C: long-lasting acidemia - K+ depletion

K+

D

K+

H+ H+

K+

D: Quick alkalisation - exchange H+ for K+ -

dangerous hypokalemia

K+

Cellular exchange K+/H+

CO2

H2OH2CO3

HCO3

-

Buf -

HBuf

CO2

H2O

H2CO3

HCO3

-

H+

Bicarbonate hardly passes throught hematoencephalic

barrier

Respiration center

CO2 passes through hematoencephalic barrier easily

H+

Qu

ick

dif

fusi

onRespiratory controller of acid-base disorders

CO2

H2OH2CO3

Buf -

HBuf

CO2

H2O

H2CO3

HCO3

-

H+

Acute metabolic acidosis

Respiration center

H+retention

H+

HCO3

-

Slow diffusion


barrier

CO2 passes through hematoencephalic barrier easilyQ

uic

k d

iffu

sion

CO2

H2OH2CO3

HCO3

-

Buf -

HBuf

CO2

H2O

H2CO3

HCO3

-

H+

Sustained metabolic acidosis

Respiration center

pH depletion - stimulation of respiration center

H+

H+retention Slow diffusion


barrier

CO2 passes through hematoencephalic barrier easilyQ

uic

k d

iffu

sion

CO2+H2O

H+

Neutral aminoacids

carboncarcass

H+

Urea

NH4+

CO2

Am

inog

roup

Glutamine

Glutamate(2-oxoglutarate)

Glutamine

NH4+

H+ +NH3 H+NH3 + H+

NH3

NH4+

Proximaltubule

Distalnephron

preferredin acidemia

preferredin acidemia

HCO3-

prefererred in alkalemia

NH4+

preferred In alkalemia

-acidémia – inhibition of enzyme activity

alkalemia – aktivation of enzyme activity

In case of liver failure this feedback is brokenTherefore there is inclination to alkalemia during liver failure Role of liver in Acid-Base

Interorgan ammonia metabolism in liver failure: the basis of current and future therapies

Liver InternationalVolume 31, Issue 2, pages 163-175, 27 JUL 2010 DOI: 10.1111/j.1478-3231.2010.02302.xhttp://onlinelibrary.wiley.com/doi/10.1111/j.1478-3231.2010.02302.x/full#f3

Atkinson: urea synthesis is dependent on pH (concentration of HCO3)Liver take part in acid-base regulation

pH

Urea synthesis is dependent on delivery of NH4+

Not proved !!!

pH

Atkinson: urea synthesis is dependent on pH (concentration of HCO3)Liver takes part in acid-base regulation

Prox. Tubul.

HCO3-

NH4+ Na+

NH4+

Glutamin

glutaminase

NH4+ NH3

H+HCO3-

CO2

CO2

NH4+

H+HCO3

-

CO2CO2

NH3NH4

+

Na+

Cl-

Cl-

Na+

NH4+

H+

H+ H++ HCO3-

Cl-NH3

NH4+

HCO3-

H+

NH4+

HCO3-

alfa-ketoglutarate

Na+

Na+

K+

Na+-K

+

ATPáza

Na+

K+

H+

OH-

CO2

H2O

CO2

H2O

H2CO3

HCO3-

H+

HCO3-

karboanhydrase

karboanhydrase

675 mmol HCO3-

/24hodproximal tubule

Na+

CAMP

ATPAC

Gs

Gi-

Angiotensin II

Parathormon

Na+

HCO3-

NH4+ Glutamine

glutaminase

+

+ Glutamine

NH4+

4500 mmol HCO3

-/24hod

3825 mmol HCO3

-/24hod

-68mV

+ -

-70mV

- +-2mV

+-

-

-

-+

Rat

e of

HC

O3- r

eabs

orbt

ion

and

excr

etio

n

8 16 20 24 28 32 36 40 mmol/lPlasma (and glomerular filtrate) HCO3

- level 4

filtere

d

HCO3-readsorbtion

Exkrece H

CO 3-

at pCO 2

= 60 torr

při pCO2 = 40 torr

at pCO2 = 60 torr

at pCO 2

= 40 torr

H+ -ATPáza

H+

karboanhydrase

CO2

H2O

H+

OH-

HCO3-

Cl-

Cl-

HCO3-

HCO3- CO2

HPO42- H2PO4

-(titratable acidity)

NH3 NH4+

-intercalar cells

lumen

+

Aldosteron

H+ -ATPázaH

+ -ATPáza

H2OH2OH+H+

OH-OH-

CO2CO2

HCO3-HCO3-

karboanhydrasekarboanhydrase

Cl-Cl-

Cl-Cl-H+H+

HCO3-HCO3-

Cl-Cl-

-intercalar cells-intercalar cells

-

+

H+

Renal acid-base controller(in distal nephron)

Na+K+

Na+-K

+

ATPáza

Cl-

Cl-Na+ K+

H+ -ATPáza

H+

karboanhydrase

CO2

H2O

H+

OH-

HCO3-

Cl-

Cl-

HCO3-

HCO3- CO2

HPO42- H2PO4

-(titratable acidity)

NH3 NH4+

H+ -ATPáza

H2OH+

OH-

CO2

HCO3-

karboanhydrase

Cl-

Cl-H+

HCO3-

Cl-

-intercalar cells-intercalar cellsmain cells

lumen

Cl-

Na+K+

++

Aldosteron

+

+

+

A-A-

(non-resorbable anion)

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

TA + NH4+

CO2 balance

H+ balance

Buffer system acid-base disturbances

Balance acid-base disturbances:

- respiration acidosis/alkalosis

- metabolic acidosis/alkalosis

Acid-base disturbances:

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

TA + NH4+

CO2 balance

H+ balance

Buffer system acid-base disturbances

Balance acid-base disturbances:

- respiration acidosis/alkalosis

- metabolic acidosis/alkalosis

Acid-base disturbances:

Balance

disorders

Balance

contro

l

Normalbalance

Balance

contro

ldisorders

Metabolic acidosis

Balance

contro

ldisorders

Metabolic alkalosis

CO2

H2O

H2CO3

HCO3

3. Respiration keep CO2 level unchangeable – thereby increases buffer power of

bicarbonate buffer

1. Primary disturbance: H+ retention

4. Pathophysiological concequence:

H+ levelincreases only a little bit

due to buffer reaction

Buf -

HBuf

-2. Consumption of bicarbonate

in buffer reaction

2. Consumtion of non-bicarbonate buffer bases in buffer reaction

Acute metabolic acidosis

PCO2

BE

H+

CO2

H2O

H2CO3

HCO3

H+

2. Respiratory response:Decrease CO2 level

1. Primary failurea: H+retention

3. Shift of equilibrium to the left

4. Pathophysiological concequence : diminished H+ level

-

Buf -

HBuf

Respiratory compensationof metabolic acidosis

PCO2

BE

-25 -20 -15 -10 -5 0 5 10 15 20 25 30

10

20

30

40

50

60

70

80

90PCO2 torr

Base Excess mmol/l

pH=7

,1

pH=7

,2

pH=7

,3

pH=7,

37

pH=7,4

3

pH=7,5

pH=7,6

Acute metabolic acidosis Akute metabolic alkalosis

Acu

te r

esp

irat

ory

acid

osi

Acute respiratory acidosis

Sustained metabolic alkalosis


Sustain

ed re

spira

tory

alkalo

sis

Sust

aine

d re

spir

ator

y ac

idos

is

CO2

H2O

H2CO3

HCO3

-

Buf -

HBuf

H+

A-

H+ retentionH+ depletion

TA+NH4+

Bicarbonate reabsorbtion

(3) losses of

HCO3

-

(4) diarhoeaH+excretion

(1) Increased metabolic production of strong acids

(2) Disorder of H+

excretion

Na+

Cl-

HCO3-

Na+

Cl-

HCO3-

Na+

Cl-

Anion gap

HCO3-

Accumulation of anions of strong acids(laktate acidosis

ketoacidosisuremic acidosis)

A- HCO3-

Cl-

H+

NH4+Cl-

NH3

H+

NH4+

NH3Cl-Relative accumulation of chlorides

Decreased acidification(tubular acidosis, hypoaldosteronisms, decreases glomer. filtration)

Normal aniongap

Increasedanion gap

Gastrointestinal losses of bicarbonate

HCO3-

Cl-

Na+

K+ Cl-

Na+

K+

Cl-

In urine:[K+]+[Na+]-[Cl-] < 0

in urine:[K+]+[Na+]-[Cl-] >= 0

Overdosis of NH4Cl

H+

Urea

HCO3-

HCO3-

Metabolic acidosis with:-increased anion gap-normal anion gap

DiarrhoeaDiarrhoea

Na+Na+ Cl-Cl- H2OH2O

HCO3-HCO3-

NHE

AE

CO2 + H2OCO2 + H2O

H+H+

HCO3-HCO3-H+H+

H+H+HCO3

-HCO3-

CO2 + H2OCO2 + H2O

Na+Na+ Cl-Cl-

Na+Na+

Cl-Cl-

H2OH2O

Normal state: reabsorbiton NaCl + water in colon

Na+Na+ Cl-Cl- H2OH2O

HCO3-HCO3-

NHE

AE

CO2 + H2OCO2 + H2O

H+H+

HCO3-HCO3-H+H+

H+H+HCO3

-HCO3-

CO2 + H2OCO2 + H2O

Na+Na+ Cl-Cl-

Na+Na+

Cl-Cl-

H2OH2O

Increased delivery (H2O, Na+, Cl-) to colon

Increased NHE and AE transport

Na+Na+ Cl-Cl-H2OH2O

HCO3-HCO3-

AE

CO2 + H2OCO2 + H2O

H+H+

HCO3-HCO3-H+H+

H+H+HCO3

-HCO3-

CO2 + H2OCO2 + H2O

Na+Na+ Cl-Cl-

Na+Na+

Cl-Cl-

H2OH2O Na+Na+

HCO3-HCO3-

NHE

Cl-Cl- HCO3-HCO3-

H2OH2O

K+K+

AE has a lager capacity then NHE

Delivery (H2O, Na+, Cl-) to colon is higher then capacity of colon reabsorbtion -> diarhoea

Alkalic diarrhoea

Hypotonic fluid lossHypotonic fluid loss

Hypertonic dehydratationHypertonic dehydratation

Hyperchloremic acidosisHyperchloremic acidosis

HCO3-HCO3-

Severe alkalic diarrhoea

Hyperchloremic acidosisHyperchloremic acidosis

HCO3-

HCO3-

Potassium lossPotassium loss



Renal tubular acidosisRenal tubular acidosis

10 15 20 25

Rat

e of

bic

arbo

nate

rea

bsor

btio

n

Plasma level of HCO3-

pH=5,5 pH=6,5 pH=7,8

Complete reabsorbtion

norm

proximal tubular renal acidosis

abc norma

abc

norm

pH=5,5

CO2

H2O

H2CO3

HCO3

-

Buf -

HBuf

H+

A-

H+ retentionH+ depletion

TA+NH4+


(3) losses of

HCO3

-

(4) diarhoeaH+excretion

(1) Increased metabolic production of strong acids

(2) Disorder of H+

excretion

CO2

H2O

H2CO3

HCO3

-

Buf -

HBuf

H+

A-

Retence H+

Retence H

TA+NH4+


(6) vomiting

H+excretion

(7) K+

depletion

hyperaldosteronism

katabolism

K+

H+

CO2

H2O

H2CO3

HCO3

H+

3. Respiration keep CO2 level unchangeable – thereby increases buffer power of

bicarbonate buffer

4. Pathophysiological concequence:

H+ leveldecreases only a little bit due to

buffer reaction

Buf -

HBuf

-

2. Dissotiation of carbonic acid in buffer reaction

2. Dissotioation of non-bicarbonate acid in

buffer reaction

Acute metabolic alkalosis

1. Primary disturbance:

H+ lossPCO2

BE

CO2

H2O

H2CO3

HCO3

H+

2. Regulatory response of respiration:

Increase level of CO2

1. Primary disturbance:

H+ loss+

4. . Pathophysiological concequence :increase diminished H+ level

Buf -

HBuf

-

3. Shift equilibrium in buffer system to the right

Respiratory compensationof metabolic alkalosis

PCO2

BE

-25 -20 -15 -10 -5 0 5 10 15 20 25 30

10

20

30

40

50

60

70

80

90PCO2 torr

Base Excess mmol/l

pH=7

,1

pH=7

,2

pH=7

,3

pH=7,

37

pH=7,4

3

pH=7,5

pH=7,6


Acu

te r

esp

irat

ory

acid

osi




Sustain

ed re

spira

tory

alkalo

sis

Sust

aine

d re

spir

ator

y ac

idos

is

VomitingVomiting

No acid-base changes

No acid-base changes

StomachStomach

CO2 H2O

HCO3-

H+

Cl-

Cl-

CO2 H2O

HCO3- H+

Cl-

CO2

H2O

BalancedBalanced

Duodenum and pancreasDuodenum and pancreas

Normal state

Normal state

H+

HCO3-

retentionHCO3

- retention

H+ lossH+ loss

Chloride loss

Chloride loss

Hypochloremic alkalosis

Hypochloremic alkalosis

StomachStomach

CO2 H2O

HCO3-

H+

Cl-

Cl-

CO2 H2O

HCO3- H+

Cl-

CO2

H2O

UnbalancedUnbalanced

Duodenum and pancreasDuodenum and pancreas

VomitoingVomitoing

H+

Cl- H+

HCO3-



H+Cl

-

H+

K+

K+

H+

K+

H+

Paradoxal urine acidification

Potassium depletion

Increases lossse ofn

Intracellular fluid

Primary cause:

Losses of Cl- a H+ by vomiting

Metabolic alkalosis

H+

Cl-

K+

K+

H+

Na+

Glomerulal filtration (hypochloremic

alkalosis)

Increased exchange Na+ with K+ and Na+ with H+

Excretion of potassium increases,acidification of urine regardless of alkalosis

Na+

Glomerular filtraton (norm)

Readsorbtion of sodium and chlorides

Depletion of chlorides

Cl-

Cl-

Na+

Na+

Remnant of sodium is exchanged with and H+

K+

K+

H+

H+

NH4+

Na+/Cl- reabsorbtion is diminished

Cl-

Na+

Na+

CO2

H2O

H2CO3

HCO3

H+

1. Primary disturbance: CO2 retention

4. Pathophysiological concequence :H+ level increases only a little bit due to buffer reaction

Buf -

HBuf

-

3. Dissociation of carbonic acid,creation of a huge amount of H+ ions


3. H+ ions are removed by the bounding with non-bicarbonate

buffer bases

2. Shift equilibrium to the left- to carbonic acid dissociation

PCO2

BE

CO2

H2O

H2CO3

HCO3

H+

1. Primární disturbance:

CO2 retention

4. Pathophysiological concequence :decrease of H+ level

Buf -

HBuf

-

3. Addition of bicarbonates shifts equilibrium to the right,

bicarbonates bind H+ ions

Renal compensation of respiratory acidosis

2. Regulatory responce of kidney:

increasing excretion of titratable acids (TA) and

ammonium ions accompanied by

equimolar addition of bicarbonate ions into

extracellular fluidTA+NH4+

Increasing of H+ level

(increased levels of CO2 and H2CO3 are set to unchangeable

values due to respiration)

PCO2

BE

-25 -20 -15 -10 -5 0 5 10 15 20 25 30

10

20

30

40

50

60

70

80

90PCO2 torr

Base Excess mmol/l

pH=7

,1

pH=7

,2

pH=7

,3

pH=7,

37

pH=7,4

3

pH=7,5

pH=7,6


Acu

te r

esp

irat

ory

acid

osi




Sustain

ed re

spira

tory

alkalo

sis

Sust

aine

d re

spir

ator

y ac

idos

is

CO2

1. Primary disturbance: CO2 depletion

4. Pathophysiological concequence : H+ level due to buffering of non-bicarbonate acids decreases only a little bit.

Buf -

HBuf

3. Due to carbonic acid production,A huge amount of H+ ions are

consumed

Acute respiratory alcalosis

3. Consumed H+ ions supplemented from non

bicarbonate buffered acids

2. Shift equlibrium to the left,(to carbonic acid production)

PCO2

BE

H2O

H2CO3

H+

HCO3-

H+

CO2

H2O

H2CO3

HCO3

H+

1. Primary disturbance: CO2 depletion

4. Pathophysiological consequence: increase of H+ level

Buf -

HBuf

-

Renal compensation of respiratory alkalosis

2. Regulatory responce of kidney:

decreasing excretion of titratable acids (TA) and

ammonium ions will be less then metabolic strong

acids production.

3. Metabolic H+

ions production is greater then

their renal excretion

(decreased levels of CO2 and H2CO3 are set to unchangeable

values due to respiration)

Decrease of H+

PCO2

BE

-25 -20 -15 -10 -5 0 5 10 15 20 25 30

10

20

30

40

50

60

70

80

90PCO2 torr

Base Excess mmol/l

pH=7

,1

pH=7

,2

pH=7

,3

pH=7,

37

pH=7,4

3

pH=7,5

pH=7,6


Acu

te r

esp

irat

ory

acid

osi




Sustain

ed re

spira

tory

alkalo

sis

Sust

aine

d re

spir

ator

y ac

idos

is

PO2

Concentration of O2

PaO2PvO2

Arterial blood at pH=7,4

Venose blood at pH=7,2

Oxygen released due to shift

of dissotiacion curve(Bohr effect)

Oxygen released due drop

PO2

PO2

Concentration of O2

High PaO2 during hyperventilation

at respiratory alkalosis

PvO2

Arterial blood at pH=7,4(normal conditions)

Venous blood at pH=7,2(normal conditions)

normal PaO2

Venous blood at pH=7,36(alkalemia)

Arterial blood at pH=7,6

(alkalemia)

Release of oxygen at normal condition

Release of oxygen at respiratory alkalosis

Decrease of oxygen delivery

to tissues at acute

respiratory alkalosis

-25 -20 -15 -10 -5 0 5 10 15 20 25 30

10

20

30

40

50

60

70

80

90PCO2 torr

Base Excess mmol/l

pH=7

,1

pH=7

,2

pH=7

,3

pH=7,

37

pH=7,4

3

pH=7,5

pH=7,6


Acu

te r

esp

irat

ory

acid

osi




Sustain

ed re

spira

tory

alkalo

sis

Sust

aine

d re

spir

ator

y ac

idos

is

Mixed acid-base disturbances - examples

Metabolic acidosis + respiratory acidosis

Metabolic acidosis + respiratory alkalosis

Diarrhoea -> metabolic acidosis + vomiting -> metabolic alkalosis+ catabolism, ->lactate metabolic acidosis

Documents

Homeostasis of internal enviroment