homeostasis of internal enviroment
DESCRIPTION
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 PresentationTRANSCRIPT
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Homeostasis of internal enviroment
Acid-base homeostasis
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1865 Claude Bernard
External environment of organism
Internal environment of the cells
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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
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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.
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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
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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
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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)
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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
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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.
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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
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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
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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
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Outputs
Inputs
StorageBalance between input and output flow
depletion
retention?
?
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extracellular fluid - ECF
intracellular fluid - ICF
Metabolism
ConcentrationsBalance estimation
External environment of organism
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plasma
interstitial fluid - ISF
intracellular fluid - ICF
Metabolism
Concentrations
extracellular fluid -ECF
capillaries
Lymph
External environment of organism
Balance estimation
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intravascularfluid
intracellular fluid - ICF
Metabolism
plasma blood cells(part of ICF)
extracellular fluid -ECF
capillaries capillaries
Lymph
External environment of organism
interstitial fluid - ISF
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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
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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
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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
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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
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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
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+
H+
OH-
H2O
H2O
H2O OH-
H3O+
+
-
-
H2O
OH-
H+
H2O
H2O OH-
H3O+
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H2O
H2O
H2O
H2O
H2O H2O
H2O
H2O
H2O
H2O
H2O
H2O
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H2O
H2O
H2O
H2O
H2O H2O
H2O
H2O
H2O
H2O
OH-
H3O+
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H2O
H2O
H2O
H2O
H2O H2O
H2O
H2O
H2O
H2O
H3O+
OH-
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H2O
H2O
H2O
H2O
H2O H2O
H2O
H2O
H2O H3O+
OH-
H2O
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H2O
H2O
H2O
H2O
H2O H2O
H2O
H2O
H2O H3O+
OH-
H2O
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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-
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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+
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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-
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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-
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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-
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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-
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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-
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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-
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H+
OH-
H2O H2O
H2O
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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+
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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+
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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
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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
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CO2
H2O
H2CO3
HCO3
H+
-A: Open system
1. Addition of strong acid (H+ ions)
CO2
H2O
H2CO3
HCO3
H+
-
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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
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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
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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!
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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
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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-
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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
-
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Buffering reactions
H2CO
3
HCO3-
H+
CO2
HBuf
Buf-
H2O
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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 )
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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
- ]
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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-
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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
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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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/54.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/55.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/56.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/57.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/58.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/59.jpg)
Measurement of Acid-Base parameters
pH, pCO2, [HCO3-]
HCO3-
H+
Buf-
HBuf
CO2
H2O
H2CO3
![Page 60: Homeostasis of internal enviroment](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/60.jpg)
pH, pCO2, [HCO3-]
HCO3-
H+
Buf-
HBuf
CO2
H2O
H2CO3
Measurement of Acid-Base parameters
![Page 61: Homeostasis of internal enviroment](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/61.jpg)
pH, pCO2, [HCO3-]
HCO3-
H+
Buf-
HBuf
CO2
H2O
H2CO3
Alkaline reserve
Measurement of Acid-Base parameters
![Page 62: Homeostasis of internal enviroment](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/62.jpg)
pH, pCO2, [HCO3-]
HCO3-
H+
Buf-
HBuf
CO2
H2O
H2CO3
P. Astrup 1956
Measurement of Acid-Base parameters
![Page 63: Homeostasis of internal enviroment](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/63.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/64.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/65.jpg)
CO2
H2O
H2CO3
HCO3
H+
Buf -
HBuf
-
+ 1 mmol H+ added to 1 litre of blood
![Page 66: Homeostasis of internal enviroment](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/66.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/67.jpg)
CO2
H2O
H2CO3
HCO3
H+
Buf -
HBuf
-
+ 1 mmol OH- added to 1 litre of blood
![Page 68: Homeostasis of internal enviroment](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/68.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/69.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/70.jpg)
reading of BE
Odečet BB
NBB=41,7 + 0,42 * cHB
![Page 71: Homeostasis of internal enviroment](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/71.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/72.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/73.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/74.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/75.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/76.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/77.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/78.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/79.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/80.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/81.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/82.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/83.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/84.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/85.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/86.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/87.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/88.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/89.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/90.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/91.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/92.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/93.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/94.jpg)
-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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/95.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/96.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/97.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/98.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/99.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/100.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/101.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/102.jpg)
-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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/103.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/104.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/105.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/106.jpg)
-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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/107.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/108.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/109.jpg)
-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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/110.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/111.jpg)
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](https://reader036.vdocuments.us/reader036/viewer/2022070415/56814e4d550346895dbbd87c/html5/thumbnails/112.jpg)
-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