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Homeostasis of internal enviromen Acid-base homeostasis

Homeostasis of internal enviroment

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Homeostasis of internal enviroment. Acid-base homeostasis. External environment of organism. 1865 Claude Bernard. Internal environment of the cells. External environment of organism. - PowerPoint PPT Presentation

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Page 1: Homeostasis of internal enviroment

Homeostasis of internal enviroment

Acid-base homeostasis

Page 2: Homeostasis of internal enviroment

1865 Claude Bernard

External environment of organism

Internal environment of the cells

Page 3: Homeostasis of internal enviroment

1865 Claude Bernard

External environment of organism

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

Page 4: Homeostasis of internal enviroment

1932 Walter Cannon

External environment of organism

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

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

Page 5: Homeostasis of internal enviroment

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

Page 6: Homeostasis of internal enviroment

1932 Walter Cannon

Arturo Rosenblueth(disciple of W. 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

Page 7: Homeostasis of internal enviroment

1932 Walter Cannon

Arturo Rosenblueth Nobert Wiener

collaboration

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

(disciple of W. Cannon)

Page 8: Homeostasis of internal enviroment

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

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

nearly „cybernetic“ definition in 1932

Page 9: Homeostasis of internal enviroment

1932 Walter Cannon

External environment of organism

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

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

Page 10: Homeostasis of internal enviroment

extracellular fluid

1932 Walter Cannon

intracellularfluid

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

Their properties must enable optimal functioning of cellular structures

External environment of cells = internal environment

External environment of organism

Page 11: Homeostasis of internal enviroment

extracellular fluid

1932 Walter Cannon

intracellularfluid

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

Their properties must enable optimal functioning of cellular structures

External environment of cells = internal environment

External environment of organism

Metabolism

Page 12: Homeostasis of internal enviroment

extracellular fluid

1932 Walter Cannon

intracellularfluid

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

Their properties must enable optimal functioning of cellular structures

External environment of cells = internal environment

External environment of organism

Metabolism

Page 13: Homeostasis of internal enviroment

Outputs

Inputs

StorageBalance between input and output flow

depletion

retention?

?

Page 14: Homeostasis of internal enviroment

extracellular fluid - ECF

intracellular fluid - ICF

Metabolism

ConcentrationsBalance estimation

External environment of organism

Page 15: Homeostasis of internal enviroment

plasma

interstitial fluid - ISF

intracellular fluid - ICF

Metabolism

Concentrations

extracellular fluid -ECF

capillaries

Lymph

External environment of organism

Balance estimation

Page 16: Homeostasis of internal enviroment

intravascularfluid

intracellular fluid - ICF

Metabolism

plasma blood cells(part of ICF)

extracellular fluid -ECF

capillaries capillaries

Lymph

External environment of organism

interstitial fluid - ISF

Page 17: Homeostasis of internal enviroment

intravascularfluid

intracellular fluid - ICF

Metabolism

plasma

capillaries

transcellular fluid

extracellular fluid -ECFcapillaries

Lymph

External environment of organism

blood cells(part of ICF)

interstitial fluid - ISF

Page 18: Homeostasis of internal enviroment

intravascularfluid

intracellular fluid - ICF

Metabolism

plasma

capillaries

Lymph

extracellular fluid -ECF

LungsGIT

Ledviny

„exc

hang

ers“

blood cells(part of ICF)

interstitial fluid - ISF transcellular fluid

External environment of organism

Page 19: Homeostasis of internal enviroment

intravascularfluid

intracellular fluid - ICF

Metabolism

plasma

capillaries

Lymph

extracellular fluid -ECF

LungGIT

Kidney

„exc

hang

ers“

Circulation„mixing“

blood cells(part of ICF)

interstitial fluid - ISF transcellular fluid

External environment of organism

Page 20: Homeostasis of internal enviroment

intravascularfluid

intracellular fluid - ICF

Metabolism

plasma

capillaries

Lymph

extracellular fluid -ECF

LungsGIT

Kidney

„exc

hang

ers“

Circulation„mixing“

blood cells(part of ICF)

interstitial fluid - ISF transcellular fluid

External environment of organism

Page 21: Homeostasis of internal enviroment

intravascularfluid

intracellular fluid - ICF

Metabolism

plasma

capillaries

Lymph

extracellular fluid -ECF

LungsGIT

Kidney

„exc

hang

ers“

Circulation„mixing“

blood cells(part of ICF)

interstitial fluid - ISF transcellular fluid

External environment of organism

CO2 H +

ACID-BASE BALANCE

Page 22: Homeostasis of internal enviroment

+

H+

OH-

H2O

H2O

H2O OH-

H3O+

+

-

-

H2O

OH-

H+

H2O

H2O OH-

H3O+

Page 23: Homeostasis of internal enviroment

H2O

H2O

H2O

H2O

H2O H2O

H2O

H2O

H2O

H2O

H2O

H2O

Page 24: Homeostasis of internal enviroment

H2O

H2O

H2O

H2O

H2O H2O

H2O

H2O

H2O

H2O

OH-

H3O+

Page 25: Homeostasis of internal enviroment

H2O

H2O

H2O

H2O

H2O H2O

H2O

H2O

H2O

H2O

H3O+

OH-

Page 26: Homeostasis of internal enviroment

H2O

H2O

H2O

H2O

H2O H2O

H2O

H2O

H2O H3O+

OH-

H2O

Page 27: Homeostasis of internal enviroment

H2O

H2O

H2O

H2O

H2O H2O

H2O

H2O

H2O H3O+

OH-

H2O

Page 28: Homeostasis of internal enviroment

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-

Page 29: Homeostasis of internal enviroment

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+

Page 30: Homeostasis of internal enviroment

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-

Page 31: Homeostasis of internal enviroment

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-

Page 32: Homeostasis of internal enviroment

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-

Page 33: Homeostasis of internal enviroment

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-

Page 34: Homeostasis of internal enviroment

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-

Page 35: Homeostasis of internal enviroment

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-

Page 36: Homeostasis of internal enviroment

H+

OH-

H2O H2O

H2O

Page 37: Homeostasis of internal enviroment

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+

Page 38: Homeostasis of internal enviroment

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+ + Buf HBuf

H+ + Buf HBuf

HBufBuf-

H+

OH-

H2O H+

Page 39: Homeostasis of internal enviroment

CO2

H2O

H2CO3

HCO3

-

H+

A-

TA+NH4

+

20 000 mmol/24 hod 60 mmol/24 hod

60 mmol/24 hH+ excretion

Practically complete reabsorbtion of HCO3-

Metabolic production od strong acidsMetabolic production of CO2

Page 40: Homeostasis of internal enviroment

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

Page 41: Homeostasis of internal enviroment

CO2

H2O

H2CO3

HCO3

H+

-A: Open system

1. Addition of strong acid (H+ ions)

CO2

H2O

H2CO3

HCO3

H+

-

Page 42: Homeostasis of internal enviroment

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

Page 43: Homeostasis of internal enviroment

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

Page 44: Homeostasis of internal enviroment

TA+NH4

+

20 000 mmol/24 hod

60 mmol/24 hodMetabolic production od strong acids

Metabolic production of CO2

CO2

H2O

H2CO3

HCO3-

H+

24 mmol/l

40 nmol/l (pH=7,40)

dHCO3 = +1 mmol/l-

dH+ = +1 mmol/l -

10-3 mol H+/l: pH=3!

Page 45: Homeostasis of internal enviroment

TA+NH4

+

20 000 mmol/24 hodMetabolic production of CO2

CO2

H2O

H2CO3

HCO3-

H+

24 mmol/l

40 nmol/l (pH=7,40)

dHCO3 = +1 mmol/l-

dH+ = +1 mmol/l -

10-3 mol H+/l: pH=3!

Buf -

HBuf

Page 46: Homeostasis of internal enviroment

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-

Page 47: Homeostasis of internal enviroment

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

-

Page 48: Homeostasis of internal enviroment

Buffering reactions

H2CO

3

HCO3-

H+

CO2

HBuf

Buf-

H2O

Page 49: Homeostasis of internal enviroment

Bicarbonate buffer

H2CO

3

HCO3-H+CO2 H2O ++

Hendersson- Hasselbalch equation:

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

or

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

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

Page 50: Homeostasis of internal enviroment

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

- ]

Page 51: Homeostasis of internal enviroment

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-

Page 52: Homeostasis of internal enviroment

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

Page 53: Homeostasis of internal enviroment

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

- ]

Page 54: Homeostasis of internal enviroment

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

- ]

dHCO3 = +1 mmol/l-

dH+ = +1 mmol/l-

Page 55: Homeostasis of internal enviroment

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-

A: Titration CO2 „in vitro“

Buffer Base (BB)

BB = [HCO3

- ]+ [Buf

- ]

Buffer Base (BB)

BB = [HCO3

- ]+ [Buf

- ]

Page 56: Homeostasis of internal enviroment

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-

A: Titration CO2 „in vitro“

Buffer Base (BB)

BB = [HCO3

- ]+ [Buf

- ] = const

Buffer Base (BB)

BB = [HCO3

- ]+ [Buf

- ] = const

999 997 nmol/l H+

were „buffered“by nonbicarbonate

buffers

Page 57: Homeostasis of internal enviroment

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

- ]

v in blood decreases

Buffer Base (BB)

BB = [HCO3

- ]+ [Buf

- ] =/= const

Buffer Base (BB)

BB = [HCO3

- ]+ [Buf

- ] =/= const

Page 58: Homeostasis of internal enviroment

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

- ]

v in blood decreases

If pCO2 increases

BB = [HCO3

- ]+ [Buf

- ]

v in blood decreases

Page 59: Homeostasis of internal enviroment

Measurement of Acid-Base parameters

pH, pCO2, [HCO3-]

HCO3-

H+

Buf-

HBuf

CO2

H2O

H2CO3

Page 60: Homeostasis of internal enviroment

pH, pCO2, [HCO3-]

HCO3-

H+

Buf-

HBuf

CO2

H2O

H2CO3

Measurement of Acid-Base parameters

Page 61: Homeostasis of internal enviroment

pH, pCO2, [HCO3-]

HCO3-

H+

Buf-

HBuf

CO2

H2O

H2CO3

Alkaline reserve

Measurement of Acid-Base parameters

Page 62: Homeostasis of internal enviroment

pH, pCO2, [HCO3-]

HCO3-

H+

Buf-

HBuf

CO2

H2O

H2CO3

P. Astrup 1956

Measurement of Acid-Base parameters

Page 63: Homeostasis of internal enviroment

Equilibration method for pCO2 measurement by Astruplog PCO

2

pH

Titration curve

pH In blood sample (before equilibrationí

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

Page 64: Homeostasis of internal enviroment

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

Page 65: Homeostasis of internal enviroment

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

+ 1 mmol H+ added to 1 litre of blood

Page 66: Homeostasis of internal enviroment

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

Page 67: Homeostasis of internal enviroment

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

+ 1 mmol OH- added to 1 litre of blood

Page 68: Homeostasis of internal enviroment

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

Page 69: Homeostasis of internal enviroment

log pCO2

pH

Plasma and blood with different hematocrit

BE=0

7.4

40 torr BE=-5

BE=-10

BE=5

BEcurve

Page 70: Homeostasis of internal enviroment

reading of BE

Odečet BB

NBB=41,7 + 0,42 * cHB

Page 71: Homeostasis of internal enviroment

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

Page 72: Homeostasis of internal enviroment

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+

Page 73: Homeostasis of internal enviroment

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

upřednostněnopři acidémii

preferredin acidemia

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

Page 74: Homeostasis of internal enviroment

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

Page 75: Homeostasis of internal enviroment

CO2

H2OH2CO3

Buf -

HBuf

CO2

H2O

H2CO3

HCO3

-

H+

Acute metabolic acidosis

Respiration center

H+retention

H+

HCO3

-

Slow diffusion

Bicarbonate hardly passes throught hematoencephalic

barrier

CO2 passes through hematoencephalic barrier easilyQ

uic

k d

iffu

sion

Page 76: Homeostasis of internal enviroment

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

Bicarbonate hardly passes throught hematoencephalic

barrier

CO2 passes through hematoencephalic barrier easilyQ

uic

k d

iffu

sion

Page 77: Homeostasis of internal enviroment

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

+-

-

-

-+

Page 78: Homeostasis of internal enviroment

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

Page 79: Homeostasis of internal enviroment

NH4+ Na+

NH4+

Glutamin

glutamináza

NH4+ NH3

H+HCO3-

CO2

CO2

NH4+

H+HCO3

-

CO2CO2

NH3NH4

+

Na+

Cl-

Cl-

Na+

NH4+

H+

H+ H++ HCO3-

Cl-NH3

NH4+

HCO3-

1

2

H+

NH4+

3

4

5

6

Page 80: Homeostasis of internal enviroment

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+ -ATPáza

H2OH+

OH-

CO2

HCO3-

karboanhydrase

Cl-

Cl-H+

HCO3-

Cl-

-intercalar cells

-

+

H+

Renal acid-base controller(in distal nephron)

Page 81: Homeostasis of internal enviroment

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)

Page 82: Homeostasis of internal enviroment

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:

Page 83: Homeostasis of internal enviroment

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

TA + NH4+

Buffers system acid-base disturbances:Dilutional acidemiaContractional alkalemiaHypoproteinemic alkalemia

CO2 balance

H+ balance

Page 84: Homeostasis of internal enviroment

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

TA + NH4+

Buffers system acid-base disturbances:Dilutional acidemia

Dilution

CO2 balance

H+ balance

Page 85: Homeostasis of internal enviroment

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

TA + NH4+

equilibrium shift

CO2 balance

H+ balance

Buffers system acid-base disturbances:Dilutional acidemia

Dilution

Page 86: Homeostasis of internal enviroment

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

TA + NH4+

Hemoconcentration

CO2 balance

H+ balance

Buffers system acid-base disturbances:Contractional alkalemia

Page 87: Homeostasis of internal enviroment

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

TA + NH4+

CO2 balance

H+ balance

Hemoconcentration

Buffers system acid-base disturbances:Contractional alkalemia

Page 88: Homeostasis of internal enviroment

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

TA + NH4+

equilibrium shift

CO2 balance

H+ balance

Hemoconcentration

Buffers system acid-base disturbances:Contractional alkalemia

Page 89: Homeostasis of internal enviroment

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

TA + NH4+

Acute hypoproteinemia

CO2 balance

H+ balance

Buffers system acid-base disturbances: Hypoproteinemic alkalemia

Page 90: Homeostasis of internal enviroment

CO2

H2O

H2CO3

HCO3

H+

Buf -

HBuf

-

TA + NH4+

Acute hypoproteinemia

equilibrium shift CO2 balance

H+ balance

Buffers system acid-base disturbances: Hypoproteinemic alkalemia

Page 91: Homeostasis of internal enviroment

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:

Page 92: Homeostasis of internal enviroment

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+

Page 93: Homeostasis of internal enviroment

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

Page 94: Homeostasis of internal enviroment

-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

Sustained metabolic acidosis

Sustain

ed re

spira

tory

alkalo

sis

Sust

aine

d re

spir

ator

y ac

idos

is

Page 95: Homeostasis of internal enviroment

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

Page 96: Homeostasis of internal enviroment

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

Page 97: Homeostasis of internal enviroment

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

Page 98: Homeostasis of internal enviroment

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

Page 99: Homeostasis of internal enviroment

CO2

H2O

H2CO3

HCO3

-

Buf -

HBuf

H+

A-

Retence H+

Retence H

TA+NH4+

Bicarbonate reabsorbtion

(6) vomiting

H+excretion

(7) K+

depletion

hyperaldosteronism

katabolism

K+

H+

Page 100: Homeostasis of internal enviroment

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

Page 101: Homeostasis of internal enviroment

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

Page 102: Homeostasis of internal enviroment

-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

Sustained metabolic acidosis

Sustain

ed re

spira

tory

alkalo

sis

Sust

aine

d re

spir

ator

y ac

idos

is

Page 103: Homeostasis of internal enviroment

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+

Page 104: Homeostasis of internal enviroment

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

Acute respiratory acidosis

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

Page 105: Homeostasis of internal enviroment

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

Page 106: Homeostasis of internal enviroment

-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

Sustained metabolic acidosis

Sustain

ed re

spira

tory

alkalo

sis

Sust

aine

d re

spir

ator

y ac

idos

is

Page 107: Homeostasis of internal enviroment

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+

Page 108: Homeostasis of internal enviroment

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

Page 109: Homeostasis of internal enviroment

-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

Sustained metabolic acidosis

Sustain

ed re

spira

tory

alkalo

sis

Sust

aine

d re

spir

ator

y ac

idos

is

Page 110: Homeostasis of internal enviroment

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

Page 111: Homeostasis of internal enviroment

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

Page 112: Homeostasis of internal enviroment

-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

Sustained metabolic acidosis

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