Homeostasis of internal enviroment
Disorders of the acid-base chemistry, influence of respiration, lungs and altered metabolism External environment of organism
1865 Claude Bernard
Internal environment of the cells External environment of organism
1865 Claude Bernard i.e. temperature, volume, osmolarity, pH, ionic composition, O2, CO2 concentrations, concentration of glucose etc.
Their properties THEY ARE STAEDY AND INDEPENDENT ON must enable optimal FLOATING CONDITIONS OF EXTERNAL ENVIRONMENT functioning of AND ON VARIED LEVELS OF CELLULAR METABOLIC cellular structures ACTIVITY External environment of cells= internal environment Homeostasis - the ability or tendency of an organism or cell to maintain internal equilibrium by adjusting its physiological processes. External environment of organism
1932 Walter Cannon i.e. temperature, volume, osmolarity, pH, ionic composition, O2, CO2 concentrations, concentration of glucose etc.
Their properties THEY ARE STAEDY AND INDEPENDENT ON must enable optimal FLOATING CONDITIONS OF functioning of EXTERNAL ENVIRONMENT AND ON VARIED LEVELS OF cellular structures CELLULAR METABOLIC ACTIVITY External environment of cells = internal environment 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 Walter Cannon 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
nearly „cybernetic“ definition in 1932 Walter Cannon 1932
Arturo Rosenblueth (disciple of W. Cannon) 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 Walter Cannon 1932
Arturo Rosenblueth Nobert Wiener (disciple of W. Cannon) 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 Walter Cannon 1932
1948: N. Wiener: Cybernetics or Control and Communication in the Animal and the Machine Arturo Rosenblueth Nobert Wiener (žák W. Cannona) collaboration Homeostasis - the ability or tendency of an organism or cell to maintain internal equilibrium by adjusting its physiological processes. External environment of organism
1932 Walter Cannon i.e. temperature, volume, osmolarity, pH, ionic composition, O2, CO2 concentrations, concentration of glucose etc.
Their properties THEY ARE STAEDY AND INDEPENDENT ON must enable optimal FLOATING CONDITIONS OF functioning of EXTERNAL ENVIRONMENT AND ON VARIED LEVELS OF cellular structures CELLULAR METABOLIC ACTIVITY External environment of cells = internal environment Homeostasis - the ability or tendency of an organism or cell to maintain internal equilibrium by adjusting its physiological processes. External environment of organism
1932 Walter Cannon
Their properties extracellular intracellular fluid must enable optimal fluid functioning of cellular structures
External environment of cells = internal environment Homeostasis - the ability or tendency of an organism or cell to maintain internal equilibrium by adjusting its physiological processes. External environment of organism
1932 Walter Cannon
Their properties extracellular intracellular fluid must enable optimal fluid functioning of cellular structures Metabolism External environment of cells = internal environment Homeostasis - the ability or tendency of an organism or cell to maintain internal equilibrium by adjusting its physiological processes. External environment of organism
1932 Walter Cannon
Their properties extracellular intracellular fluid must enable optimal fluid functioning of cellular structures Metabolism External environment of cells = internal environment Inputs
Balance between input and output flow Storage ? retention Outputs ? depletion External environment of organism Balance estimation Concentrations
extracellular fluid - ECF
intracellular fluid - ICF
Metabolism External environment of organism Balance estimation Concentrations Lymph plasma capillaries extracellular fluid -ECF interstitial fluid - ISF
intracellular fluid - ICF
Metabolism External environment of organism
plasma blood cells intravascular Lymph (part of ICF) fluid capillaries capillaries extracellular fluid -ECF interstitial fluid - ISF
intracellular fluid - ICF
Metabolism External environment of organism
plasma blood cells intravascular Lymph (part of ICF) fluid capillaries capillaries extracellular fluid -ECF
interstitial fluid - ISF transcellular fluid
intracellular fluid - ICF
Metabolism External environment of organism
GIT Lungs Kidney „exchangers“
plasma blood cells intravascular Lymph (part of ICF) fluid capillaries extracellular fluid -ECF
interstitial fluid - ISF transcellular fluid
intracellular fluid - ICF
Metabolism External environment of organism
GIT Lungs Kidney „exchangers“
plasma blood cells intravascular Lymph (part of ICF) fluid „mixing“ Circulation capillaries extracellular fluid -ECF
interstitial fluid - ISF transcellular fluid
intracellular fluid - ICF
Metabolism External environment of organism
GIT Lungs Kidney „exchangers“
plasma blood cells intravascular Lymph (part of ICF) fluid „mixing“ Circulation capillaries extracellular fluid -ECF
interstitial fluid - ISF transcellular fluid
intracellular fluid - ICF
Metabolism External environment of organism
GIT Lungs Kidney „exchangers“
plasma blood cells intravascular Lymph (part of ICF) fluid „mixing“ Circulation capillaries extracellular fluid -ECF
interstitial fluid - ISF transcellular fluid CO2 H +
intracellular fluid - ICF ACID-BASE BALANCE Metabolism H+ + H2O H+ - H O OH 2 - OH-
+ H2O H3O H O 2 + H O+ - 3 H2O OH - OH- H2O H2O
H2O
H2O H2O
H2O H2O H2O
H2O H2O
H2O H2O H2O
H2O
H2O H2O
+ H2O H3O H2O
OH- H2O
H2O H2O H2O
H2O
H2O H2O
+ H3O H2O H2O
- OH H2O
H2O H2O H2O
H2O
+ H3O H2O
H2O
H2O H2O
- OH H2O
H2O H2O H2O
H2O
+ H3O H2O
H2O
H2O H2O
- H2O OH
H2O H2O H2O H2O H2O H O 2 H2O + H2O H3O
H2O
+ + H3O + H2O H2O + H3O
H2O
H2O H2O H2O H2O H O H2O OH- 2 H2O
- - OH + H2O H2O + OH H2O H2O H2O H O 2 H2O H2O H2O + H3O
+ + H3O + H2O H2O + H3O
H2O
- OH H2O H2O H2O H2O H2O H2O H2O
- - OH + H2O H2O + OH H2O + H2O H3O H O 2 H2O H2O H2O
H2O
+ + H3O + H2O H2O + H3O
H2O
- OH H2O H2O H2O H2O H2O H2O H2O
- - OH + H2O H2O + OH H2O H2O H2O H O+ 3 H2O H2O H2O
H2O
+ + H3O + H2O H2O + H3O
H2O
H2O H2O H2O H2O H2O H2O H2O OH-
- - OH + H2O H2O + OH + H2O H3O H2O H O 2 H2O H2O H2O
H2O
+ + H3O + H2O H2O + H3O
H2O
H2O H2O H2O H2O H2O H2O H2O OH-
- - OH + H2O H2O + OH H2O H2O H2O
H2O + H O H3O 2 H2O
H2O
+ + H3O + H2O H2O + H3O
H2O
H2O - H2O OH H2O H2O H2O H2O H2O
- - OH + H2O H2O + OH + H3O H2O H2O
H2O H O H2O 2 H2O
H2O
+ + H3O + H2O H2O + H3O
H2O
H2O - H2O OH H2O H2O H2O H2O H2O
- - OH + H2O H2O + OH H2O H2O H2O + H2O H O H2O 3 H2O
H2O
+ + H3O + H2O H2O + H3O
H2O
H2O H2O H2O H2O H2O H O 2 - H2O OH
- - OH + H2O H2O + OH H+
H2O H2O - H O OH 2 H+ + H3O H2O OH- OH-
v1=k1[H2O] H O H+ + OH- 2 v =k [H+][OH-] 2 2 pH = 7.4 + -7,4 [H ] = 10 mol/l ´= 40 nmol/l v1=v2
+ - + k1[H2O] =k2[H ][OH ] pH= -log [H ]
k [H+][OH-] K‘ = 1 = k2 [H2O]
+ - K‘ [H2O] = [H ][OH ] + -7 [H ] = 1,55 10 mol/l ´= 155 nmol/l [H2O] = constant - -7 [OH ] = 1,55 10 mol/l ´= 155 nmol/l + - -14 2 2 Kw = [H ][OH ] = 2,4 10 mol /l at 37°C H+ + H3O H2O OH- OH-
v1=k1[H2O] H O H+ + OH- 2 v =k [H+][OH-] 2 2 pH = 7.4 + -7,4 [H ] = 10 mol/l ´= 40 nmol/l v1=v2
+ - + k1[H2O] =k2[H ][OH ] pH= -log [H ]
k [H+][OH-] K‘ = 1 = k2 [H2O]
+ - K‘ [H2O] = [H ][OH ] + -7 [H ] = 1,55 10 mol/l ´= 155 nmol/l [H2O] = constant - -7 [OH ] = 1,55 10 mol/l ´= 155 nmol/l + - -14 2 2 Kw = [H ][OH ] = 2,4 10 mol /l at 37°C H+ Buffer curve H+ H+ pH H20 OH- OH- Cl-
+ - H + OH H2O
Addition of OH- mmol/l Addition of H+ mmol/l
-7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 5 6 7 Buffer curve Na+ + H+ pH H20 OH- OH- OH-
+ - H + OH H2O
Addition of OH- mmol/l Addition of H+ mmol/l
-7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 5 6 7 OH- Buffer curve H+ pH H2O HBuf Buf-
H+ + Buf HBuf
H+ + Buf HBuf
Addition of OH- mmol/l Addition of H+ mmol/l
-7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 5 6 7 - Practically complete reabsorbtion of HCO3
H+ excretion 60 mmol/24 h
- CO2 HCO3
+ H2CO3 TA+NH4
+ H2O H
- A
20 000 mmol/24 hod 60 mmol/24 hod
Metabolic production of CO2 Metabolic production od strong acids A: Closed system - CO2 HCO3
1. Addition of strong acid (H+ ions) H2CO3
+ H H2O
- CO2 HCO3 2. Consumption of bicarbonate and added H+ ions H2CO3 in buffer reaction
3. Establishment of new equilibriom with + increased H H2O concentrations of CO2 and H2CO3 A: Open system - CO2 HCO3
1. Addition of strong acid (H+ ions) H2CO3
+ H H2O
- CO2 HCO3
H2CO3
+ H H2O - 24 mmol/l CO2 HCO3
+ TA+NH4
H2CO3
+ 40 nmol/l (pH=7,40) H2O H
20 000 mmol/24 hod
Metabolic production of CO2 60 mmol/24 hod Metabolic production od strong acids - 24 mmol/l CO2 HCO3
+ TA+NH4
H2CO3
+ 40 nmol/l (pH=7,40) H2O H
20 000 mmol/24 hod
Metabolic production of CO2 60 mmol/24 hod Metabolic production od strong acids - dHCO3 = + 60 nmol/l
- 24 mmol/l CO2 HCO3
+ TA+NH4
H2CO3
+ 60 nmol/l (pH=7,2) H2O H +1 mmol/l
20 000 mmol/24 hod
Metabolic production of CO2 - dHCO3 = +1 mmol/l
- 24 mmol/l CO2 HCO3
+ TA+NH4
H2CO3 60 nmol/l (pH=7,2)
+ 43 nmol/l (pH=7,37) H2O H +1 mmol/l
HBuf - 20 000 mmol/24 hod dBuf = -1 mmol/l Metabolic production of CO2 - Buf Buffering systems of the blood
+ - CO2 + H2O H2CO3 H + HCO3
H+ + Buf- HBuf
H+ + Hb- HHb H+ + Alb- HAlb
+ 2- - H + HPO4 H2PO4 non-bicarbonate buffers - Buf = Hb + Alb + PO4 Buffering reactions
- CO2 HCO3
H2CO3
H2O H+ HBuf
Buf- Bicarbonate buffer
+ - CO2 + H2O H2CO3 H + HCO3 Hendersson- Hasselbalch equation:
+ - [H ] = 24 . pCO2 / [HCO3 ]
or - pH = 6.1 + log ( [HCO3 ] / [H2CO3] ) - = 6.1 + log ( [HCO3 ] / 0.03 pCO2 ) - CO2 HCO3
H2CO3
+ 40 nmol/l (pH=7,40) H2O H
HBuf
- Buf Buffer Base (BB) - - BB = [HCO3 ]+ [Buf ] - CO2 HCO3
H2CO3 - dH+ = +1 mmol/l
+ 40 nmol/l (pH=7,40) H2O H
HBuf
- Buf Buffer Base (BB) - - BB = [HCO3 ]+ [Buf ] dHCO - 3 - CO2 HCO3
H CO 2 3 dH+ = +1 mmol/l - - dBuf + dHCO3 = -1mmol/l
+ 43 nmol/l (pH=7,37) H2O H
HBuf - dBuf - Buf Buffer Base (BB) - - BB = [HCO3 ]+ [Buf ] A: Titration CO2 „in vitro“
- 24 mmol/l CO2 HCO3
H2CO3
+ 40 nmol/l (pH=7,40) H2O H
HBuf
- Buf Buffer Base (BB) - - BB = [HCO3 ]+ [Buf ] A: Titration CO2 „in vitro“
- dHCO3 = +1 mmol/l
- 24 mmol/l CO2 HCO3
H2CO3 - dH+ = +1 mmol/l
+ 40 nmol/l (pH=7,40) H2O H
HBuf
- Buf Buffer Base (BB) - - BB = [HCO3 ]+ [Buf ] A: Titration CO2 „in vitro“
- dHCO3 = +1 mmol/l
- 24 mmol/l CO2 HCO3
H2CO3
+ 43 nmol/l (pH=7,37) H2O H +1 mmol/l
HBuf - dBuf = -1 mmol/l - Buf Buffer Base (BB) - - BB = [HCO3 ]+ [Buf ] A: Titration CO2 „in vitro“
- dHCO3 = +1 mmol/l
- 24 mmol/l CO HCO3 2 999 997 nmol/l H+ were „buffered“ by nonbicarbonate buffers H2CO3 +1 mmol/l = 1 000 000 nmol/l + 43 nmol/l (pH=7,37) H2O H +1 mmol/l
HBuf - dBuf = -1 mmol/l - Buf Buffer Base (BB) - - BB = [HCO3 ]+ [Buf ] = const B: Titration CO2 „in vivo“
- CO2 HCO3
H2CO3 + H2O H
If pCO2 increases - - HBuf BB = [HCO3 ]+ [Buf ] - v in blood decreases Buf
Buffer Base (BB) - - BB = [HCO3 ]+ [Buf ] =/= const B: Titration CO2 „in vivo“
Diffusion by concentration - gradient CO2 HCO3
H2CO3 + H2O H
If pCO2 increases - - HBuf BB = [HCO3 ]+ [Buf ] - v in blood decreases Buf
- CO2 HCO3
H2CO3 + H2O H HBuf - Buf There are small concentrations of non bicarbonate buffers in ISF Measurement of Acid-Base parameters
- pH, pCO2, [HCO3 ]
- CO2 HCO3
H2CO3
+ H2O H
HBuf
Buf- Measurement of Acid-Base parameters
- pH, pCO2, [HCO3 ]
- CO2 HCO3
H2CO3
+ H2O H
HBuf
Buf- Measurement of Acid-Base parameters
- pH, pCO2, [HCO3 ] Alkaline reserve
- CO2 HCO3
H2CO3
+ H2O H
HBuf
Buf- Measurement of Acid-Base parameters
- P. Astrup pH, pCO2, [HCO3 ] 1956
- CO2 HCO3
H2CO3
+ H2O H
HBuf
Buf- Equilibration method for pCO2 measurement by Astrup log PCO 2
High level
pCO2 in mixture O2/CO2
Titration curve pCO2 in measered sample
Low level
pCO2 In mixture O2/CO2
pH
pH after equilibration pH In blood sample pH after equilibration with high pCO í 2 (before equilibration with low pCO2 Buffer Base (BB) - - BB = [HCO3 ]+ [Buf ]
CO2 HCO- depends on cHb 3
H2CO3
+ H2O H
Normal buffer base: HBuf NBB=41.7+0.42*cHB [g/100ml]
- Buf Base Excess: BE=BB-NBB CO - 2 HCO3
+ 1 mmol H+ added to 1 litre H CO 2 3 of blood
+ H2O H
HBuf
- Buf CO - 2 HCO3
+ 1 mmol H+ added to 1 litre H CO 2 3 of blood
+ H2O H
- - HBuf 1 mmol/l drop of [HCO3 ] + [Buf ]
- Buf BE=-1mmol/l CO - 2 HCO3
- H CO + 1 mmol OH added to 1 litre 2 3 of blood
+ H2O H
HBuf
- Buf CO - 2 HCO3
- H CO + 1 mmol OH added to 1 litre 2 3 of blood
+ H2O H
- - HBuf 1 mmol/l increase of [HCO3 ] + [Buf ]
- Buf BE= 1mmol/l log pCO2 Plasma and blood with different hematocrit
BE BE=0 curve 40 torr BE=-5 BE=5
BE=-10
7.4 pH NBB=41,7 + 0,42 * cHB
Odečet BB
reading of BE Acid-base regulation
CO - 2 HCO3
+ TA + NH4 H2CO3
CO2 balance + H2O H
1. Buffer systems (msec) H+ balance HBuf 2. Respiration control (12 hours) 3. Kidney control (3-5 days) - Buf
Exchange H+/K+ H+/Na+ between cells and ECF Role of liver in AB regulation K+mmol/l + + 8 Cellular exchange K /H 7 n H+ H+ orm 6 al k ale B mi + a ra K+ 5 nge K 4 A C 3 D 2
1 A: Norm
pH 6,9 7,0 7,1 7,2 7,3 7,4 7,5 7,6 7,7 7,8
+ + + H H H+ H H+ H+
+ K+ K+ K K+ K+ K+
K+ + D: Quick alkalisation - B: Acidemia - K C: long-lasting acidemia - exchange H+ for K+ - exchange K+ for H+ K+ K+ depletion dangerous hypokalemia In case of liver failure this feedback is broken Therefore there is inclination to alkalemia during liver failure Urea Role of liver in Acid-Base
H+
ity activ yme ity f enz activ ion o yme hibit f enz - – in on o émia tivati prefererred acid – ak emia alkal in alkalemia H+ CO2 NH + Glutamate 4 NH + 4 (2-oxoglutarate) CO +H O preferred 2 2 preferred Glutamine In alkalemia in acidemia up o r Proximal g o tubule in Glutamine NH + Distal Am 4 nephron
carbon + NH + H+ + H +NH3 3 H carcass preferred in acidemia NH3 + Neutral aminoacids NH4 Respiratory controller of acid-base disorders
Respiration center
+ CO2 H
H2CO3 H2O - HCO3
CO2 passes through hematoencephalic Bicarbonate hardly passes barrier easily throught hematoencephalic Quick diffusion barrier
- HCO3
CO2 H2CO3 + H H2O HBuf - Buf Acute metabolic acidosis
Respiration center
+ CO2 H
H2CO3 H2O - HCO3
CO2 passes through hematoencephalic Bicarbonate hardly passes barrier easily throught hematoencephalic Quick diffusion barrier H+retention Slow diffusion - HCO3
CO2 H2CO3 + H H2O HBuf - Buf Sustained metabolic acidosis pH depletion - stimulation of respiration center Respiration center
+ CO2 H
H2CO3 H2O - HCO3
CO2 passes through hematoencephalic Bicarbonate hardly passes barrier easily throught hematoencephalic Quick diffusion barrier H+retention Slow diffusion - HCO3
CO2 H2CO3 + H H2O HBuf - Buf -68mV -2mV -70mV 4500 mmol - glutaminase + - + - - + HCO3 /24hod + NH4 Glutamine Glutamine + - Na+ Na+-K+ + ATPáza NH4 + + - + K K HCO3 Na
Angiotensin II Na+ Gi - - CAMP + + - H+ H AC ATP + Parathormon Gs H2O H2O OH- Na+ Na+ karboanhydrase H2CO3 - - HCO3 HCO3 karboanhydrase 3825 mmol CO - - 2 CO 2 HCO3 /24hod 675 mmol HCO3 /24hod proximal tubule - Rate of HCO3 reabsorbtion and excretion 4 Plasma 8 (and glomerular filtrate)
62 42 23 40 36 32 28 24 20 16
H C HCO O f 3 ilte
E -
r e x p
3 re ř
k a i pCO - at pCO d r a d level e t p a c C s t e o p O 2
= 40torr C r H 2 2 mmol/l = O b = 60torr 2 C 4 = 0 t
t i 6 O o o 0 r - r to 3 n rr Glutamin glutaminase
+ + CO2 CO2 NH4 Na 5 + - NH4 HCO3 1 + Na+ H+ NH4 + + NH + 4 NH4 NH3 H Cl- 3 Cl-
+ H Na+ 4
+ NH4 CO2 6 CO2 - NH3 Cl + + - - H H + HCO3 HCO3 - + HCO3 H 2 NH + 4 NH3 + NH4 Renal acid-base controller α-intercalar cells β-intercalar cells + - (in distal nephron) - - H Cl HCO3 Cl Aldosteron - Cl- CO2 - karboanhydrase + HCO3 H -ATPáza OH- H+ H O 2 H2O - H+ OH + + - H -ATPáza H karboanhydrase HCO3 - CO2 Cl + +
+ H - - - HCO3 Cl HCO3 CO2 2- H PO - (titratable acidity) lumen HPO4 2 4 + NH3 NH4 main cells α-intercalar cells β-intercalar cells + - + + Cl Na K - - - H Cl HCO3 Cl Aldosteron
+ - + Cl CO2 - + + karboanhydrase + Na -K HCO3 H -ATPáza ATPáza OH- H+ H O 2 H2O + + Na K + - H OH + - H -ATPáza karboanhydrase HCO3 - CO2 Cl + + +
(non-resorbable anion) + + + - - Na K H A A - - - HCO3 Cl HCO3 CO2 2- H PO - (titratable acidity) lumen HPO4 2 4 + NH3 NH4 Cl- Cl- Acid-base disturbances:
CO - 2 HCO3
+ TA + NH4 H2CO3
CO2 balance + H2O H
H+ balance HBuf
Buffer system acid-base disturbances - Balance acid-base disturbances: Buf - metabolic acidosis/alkalosis - respiration acidosis/alkalosis CO - 2 HCO3
+ TA + NH4 H2CO3
CO2 balance + H2O H
H+ balance HBuf
Buffers system acid-base disturbances: - Dilutional acidemia Buf Contractional alkalemia Hypoproteinemic alkalemia Dilution
CO - 2 HCO3
+ TA + NH4 H2CO3
CO2 balance + H2O H
H+ balance HBuf
Buffers system acid-base disturbances: - Dilutional acidemia Buf Dilution
CO equilibrium shift - 2 HCO3
+ TA + NH4 H2CO3
CO2 balance + H2O H
H+ balance HBuf
Buffers system acid-base disturbances: - Dilutional acidemia Buf Hemoconcentration
CO - 2 HCO3
+ TA + NH4 H2CO3
CO2 balance + H2O H
H+ balance HBuf
Buffers system acid-base disturbances: - Contractional alkalemia Buf Hemoconcentration
CO2 - HCO3
+ TA + NH4 H2CO3
CO2 balance + H2O H
H+ balance HBuf
Buffers system acid-base disturbances: - Contractional alkalemia Buf Hemoconcentration
CO2 - equilibrium shift HCO3
+ TA + NH4 H2CO3
CO2 balance + H2O H
H+ balance HBuf
Buffers system acid-base disturbances: - Contractional alkalemia Buf Acute hypoproteinemia
CO - 2 HCO3
+ TA + NH4 H2CO3
CO2 balance + H2O H
H+ balance HBuf
Buffers system acid-base disturbances: - Hypoproteinemic alkalemia Buf Acute hypoproteinemia
CO - 2 HCO3
+ TA + NH4 H2CO3 equilibrium shift CO2 balance + H2O H
H+ balance HBuf
Buffers system acid-base disturbances: - Hypoproteinemic alkalemia Buf Acid-base disturbances:
CO - 2 HCO3
+ TA + NH4 H2CO3
CO2 balance + H2O H
H+ balance HBuf
Buffer system acid-base disturbances - Balance acid-base disturbances: Buf - metabolic acidosis/alkalosis - respiration acidosis/alkalosis Acute metabolic acidosis
3. Respiration keep CO2 level unchangeable – thereby increases buffer power of bicarbonate buffer 2. Consumption of bicarbonate - in buffer reaction CO2 HCO3
H2CO3 1. Primary disturbance: H+ retention + H H2O
4. Pathophysiological concequence: H+ level HBuf PCO2 increases only a little bit due to buffer reaction
- Buf
2. Consumtion of non-bicarbonate BE buffer bases in buffer reaction Respiratory compensation of metabolic acidosis 2. Respiratory response:
Decrease CO2 level
CO - 2 HCO3
H2CO3 1. Primary failurea: H+retention + H H2O 4. Pathophysiological concequence : diminished H+ level 3. Shift of equilibrium to the left HBuf
PCO2
- Buf
BE CO torr P 2 90 s 1 i , A 2 , ,3 s 7 3 7 7 o 3 c 7 , 4 d 7 , u = 7 = i = = H= te H c p H H H p p a p p ,5 80 r y 7 e r = s o H p t p
i a r r i a p t s 70 o e ,6 r 7 r = y d H p a e sis c n i lo i a d a k 60 t al o s ic s u ol i b s S eta d m 50 ine sta Su
40 Acute metabolic acidosis Akute metabolic alkalosis
sis i lo s
o sis a o k d 30 d al i aci y c c r a i
ol o e t
ab at y r
et ir u o m c d sp t
e A 20 in re a a r
t i us ed S n p i s
ta e
s r u 10 S
-25 -20 -15 -10 -5 0 5 10 15 20 25 30 Base Excess mmol/l Bicarbonate reabsorbtion (2) Disorder of H+ H+excretion excretion (4) diarhoea
- CO2 HCO3 (3) losses of - HCO3 + TA+NH4 H2CO3 H+ retention H+ depletion
+ H2O H
- HBuf A
- Buf
(1) Increased metabolic production of strong acids Gastrointestinal NH3 Metabolic acidosis with: losses of bicarbonate + -increased anion gap - - H A HCO3 -normal anion gap Cl- H+ Accumulation of anions of strong acids (laktate acidosis Cl- NH + ketoacidosis Urea 4 uremic acidosis) Overdosis of NH4Cl K+ Cl- Normal Na+ Anion Increased anion gap anion gap In urine: gap HCO - [K+]+[Na+]-[Cl-] < 0 - 3 HCO3 - HCO3 Relative - accumulation of Cl NH3 chlorides HCO3
- HCO3 H+ Na+ Na+ Na+ - Cl - - - Decreased acidification HCO3 Cl Cl (tubular acidosis, Cl- + hypoaldosteronisms, NH4 decreases glomer. filtration) K+ - + Cl in urine: Na [K+]+[Na+]-[Cl-] >= 0
Alkalic diarrhoea Severe alkalic diarrhoea Severe alkalic diarrhoea Acidic diarrhoea in DRA, down-regulated adenoma on bti or bs ea norm e r let mp norm Co proximal tubular renal acidosis c b a Rate of bicarbonate reabsorbtion - 10 15 20 25 Plasma level of HCO3
c b a norma pH=5,5 pH=6,5 pH=7,8 pH=5,5 Bicarbonate reabsorbtion (2) Disorder of H+ H+excretion excretion (4) diarhoea
- CO2 HCO3 (3) losses of - HCO3 + TA+NH4 H2CO3 H+ retention H+ depletion
+ H2O H
- HBuf A
- Buf
(1) Increased metabolic production of strong acids Bicarbonate reabsorbtion
H+excretion
- CO2 HCO3
+ TA+NH4 H2CO3 Retence H+ Retence H
+ H2O H
- HBuf A hyperaldosteronism katabolism - Buf (7) K+ depletion (6) vomiting + + H K Acute metabolic alkalosis
3. Respiration keep CO2 level unchangeable – thereby increases buffer power of bicarbonate buffer CO - 2 HCO3
H CO 2. Dissotiation of carbonic 2 3 acid in buffer reaction
4. Pathophysiological + H O concequence: 2. Dissotioation of non- 2 + H H level bicarbonate acid in decreases only a little bit due to buffer reaction buffer reaction 1. Primary disturbance: H+ loss HBuf PCO2
- Buf
BE Respiratory compensation 2. Regulatory response of respiration: of metabolic alkalosis
Increase level of CO2 3. Shift equilibrium in buffer system to the right CO - 2 HCO3
H2CO3 4. . Pathophysiological concequence : + + increase diminished H level H2O H
1. Primary disturbance: + PCO2 H loss + HBuf
- Buf
BE CO torr P 2 90 s 1 i , A 2 , ,3 s 7 3 7 7 o 3 c 7 , 4 d 7 , u = 7 = i = = H= te H c p H H H p p a p p ,5 80 r y 7 e r = s o H p t p
i a r r i a p t s 70 o e ,6 r 7 r = y d H p a e sis c n i lo i a d a k 60 t al o s ic s u ol i b s S eta d m 50 ine sta Su
40 Acute metabolic acidosis Akute metabolic alkalosis
sis i lo s
o sis a o k d 30 d al i aci y c c r a i
ol o e t
ab at y r
et ir u o m c d sp t
e A 20 in re a a r
t i us ed S n p i s
ta e
s r u 10 S
-25 -20 -15 -10 -5 0 5 10 15 20 25 30 Base Excess mmol/l Primary cause: + Glomerular filtraton Losses of Cl- a H+ (norm) Glomerulal filtration Na by vomiting + (hypochloremic - Na alkalosis) - Cl Depletion of Cl - chlorides Cl + Readsorbtion of H Na+/Cl- sodium and reabsorbtion is Metabolic diminished chlorides + + alkalosis + + Na Na - - H H Cl + + Cl Remnant of K K Increased exchange sodium is Intracellular Na+ with K+ and Na+ exchanged with fluid + + with H+ + and H K + Potassium depletion K Na + + Na H + H
Excretion of potassium increases, + + K + + + acidification of H H K K + urine regardless Paradoxal urine Increases lossse ofn H of alkalosis + NH4 acidification Acute respiratory acidosis 1. Primary disturbance:
CO2 retention
2. Shift equilibrium to the left - to carbonic acid dissociation - CO2 HCO3
3. Dissociation of carbonic acid, creation of a huge amount of H+ ions H2CO3
+ H H2O 4. Pathophysiological concequence : H+ level increases only a little bit HBuf PCO2 due to buffer reaction
- Buf
3. H+ ions are removed by the BE bounding with non-bicarbonate buffer bases Renal compensation of respiratory acidosis
2. Regulatory responce of 1. Primární kidney: disturbance: increasing excretion of CO2 retention titratable acids (TA) and (increased levels of CO and ammonium ions 2 accompanied by H2CO3 are set to unchangeable values due to respiration) - equimolar addition of bicarbonate ions into CO2 HCO3 + extracellular fluid TA+NH4 3. Addition of bicarbonates shifts equilibrium to the right, bicarbonates bind H+ ions H2CO3
+ Increasing of H+ level H2O H
4. Pathophysiological PCO2 concequence : decrease of H+ level HBuf
- Buf BE CO torr P 2 90 s 1 i , A 2 , ,3 s 7 3 7 7 o 3 c 7 , 4 d 7 , u = 7 = i = = H= te H c p H H H p p a p p ,5 80 r y 7 e r = s o H p t p
i a r r i a p t s 70 o e ,6 r 7 r = y d H p a e sis c n i lo i a d a k 60 t al o s ic s u ol i b s S eta d m 50 ine sta Su
40 Acute metabolic acidosis Akute metabolic alkalosis
sis i lo s
o sis a o k d 30 d al i aci y c c r a i
ol o e t
ab at y r
et ir u o m c d sp t
e A 20 in re a a r
t i us ed S n p i s
ta e
s r u 10 S
-25 -20 -15 -10 -5 0 5 10 15 20 25 30 Base Excess mmol/l Acute respiratory alcalosis 1. Primary disturbance:
CO2 depletion
2. Shift equlibrium to the left, (to carbonic acid production) - CO2 HCO3
3. Due to carbonic acid production, H CO A huge amount of H+ ions are 2 3 consumed 3. Consumed H+ ions supplemented from non ++ bicarbonate buffered acids H2O HH 4. Pathophysiological concequence : H+ level due to buffering of non-bicarbonate acids HBuf PCO2 decreases only a little bit.
- Buf
BE Renal compensation of respiratory alkalosis
1. Primary disturbance: 2. Regulatory responce of CO2 depletion kidney: decreasing excretion of (decreased levels of CO and 2 titratable acids (TA) and H CO are set to unchangeable 2 3 ammonium ions will be values due to respiration) - CO HCO less then metabolic strong 2 3 acids production.
3. Metabolic H+ H CO ions production 2 3 is greater then their renal excretion Decrease of H+ + H O H 2 4. Pathophysiological consequence: increase of H+ level
HBuf PCO2
- Buf
BE CO torr P 2 90 s 1 i , A 2 , ,3 s 7 3 7 7 o 3 c 7 , 4 d 7 , u = 7 = i = = H= te H c p H H H p p a p p ,5 80 r y 7 e r = s o H p t p
i a r r i a p t s 70 o e ,6 r 7 r = y d H p a e sis c n i lo i a d a k 60 t al o s ic s u ol i b s S eta d m 50 ine sta Su
40 Acute metabolic acidosis Akute metabolic alkalosis
sis i lo s
o sis a o k d 30 d al i aci y c c r a i
ol o e t
ab at y r
et ir u o m c d sp t
e A 20 in re a a r
t i us ed S n p i s
ta e
s r u 10 S
-25 -20 -15 -10 -5 0 5 10 15 20 25 30 Base Excess mmol/l Arterial blood at pH=7,4
Concentration of O2 Oxygen released due drop
PO2
Oxygen released due to shift of dissotiacion curve (Bohr effect) Venose blood at pH=7,2
PO2 PvO2 PaO2 Arterial blood Release of oxygen Arterial blood at pH=7,4 at pH=7,6 at respiratory alkalosis (normal conditions) (alkalemia) Concentration of O2
Release of oxygen at normal condition
Venous blood at pH=7,36 (alkalemia)
Venous blood at pH=7,2 (normal conditions)
Decrease of oxygen delivery to tissues at PO2 acute PvO normal PaO2 2 High PaO during respiratory alkalosis 2 hyperventilation at respiratory alkalosis Mixed acid-base disturbances - examples CO torr P 2 90 s 1 i , A 2 , ,3 s 7 3 7 7 o 3 c 7 , 4 d 7 , u = 7 = i = = H= te H c p H H H p p a p p ,5 80 r y 7 e r = s o H p t p
i a r r i a p t s 70 o e ,6 r 7 r = y d H p a e sis Metabolic acidosis c n i lo i a d a k 60 t al o + respiratory acidosis s ic s u ol i b s S eta d m 50 ine sta Su
40 Acute metabolic acidosis Akute metabolic alkalosis
sis i lo s
o sis a o k d 30 d al i aci y c c r a i
ol o e t
ab at y r
et ir u o m c d sp t
e A 20 in re a a r
t i metabolic acidosis us ed Diarrhoea -> S n p i s
ta e + vomiting -> metabolic alkalosis
s r u 10 S Metabolic acidosis + catabolism, ->lactate metabolic acidosi + respiratory alkalosis -25 -20 -15 -10 -5 0 5 10 15 20 25 30 Base Excess mmol/l