advanced physiology acid base balance instructor terry wiseth
TRANSCRIPT
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ADVANCED ADVANCED PHYSIOLOGYPHYSIOLOGY
ACID BASE ACID BASE BALANCEBALANCE
InstructorTerry WisethInstructorTerry Wiseth
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ACID BASE HOMEOSTASISACID BASE HOMEOSTASIS
Acid-base homeostasis involves chemicalchemical and physiologicphysiologic processes responsible for the maintenance of the acidity of body fluids at levels that allow optimal function of the whole individual
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ACID BASE HOMEOSTASISACID BASE HOMEOSTASIS
The chemical processeschemical processes represent the first line of defense to an acid or base load and include the extracellular and intracellularintracellular buffersbuffers
The physiologic processesphysiologic processes modulate acid-base composition by changes in cellular metabolism and by adaptive responses in the excretionexcretion of volatile acids by the lungslungs and fixed acids by the kidneyskidneys
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ACID BASE HOMEOSTASISACID BASE HOMEOSTASIS
The need for the existence of multiple mechanisms involved in acid-base regulation stems from the critical importance of the hydrogen ion (H+) concentration on the operation of many cellular enzymes and function of vital organs, most prominently the brain and the heart
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ACID BASE HOMEOSTASISACID BASE HOMEOSTASIS
The task imposed on the mechanisms that maintain acid-base homeostasis is large, since metabolic pathways are continuously consuming or producing HH++, and the daily load of waste products for excretion in the form of volatile and fixed acids is substantial
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EFFECTS OF pHEFFECTS OF pHThe most general effect of pH changes
are on enzyme functionAlso affect excitability of nerve and
muscle cells
pHpH
ExcitabilityExcitability
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ACID-BASE BALANCEACID-BASE BALANCE
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ACID-BASE BALANCEACID-BASE BALANCE
Acid - Base balance is mainly concerned with two ions:HydrogenHydrogen (H+)
BicarbonateBicarbonate (HCO3- )
H+ HCO3-
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ACID-BASE BALANCEACID-BASE BALANCEDerangements
of hydrogen and bicarbonate concentrations in body fluids are common in disease processes
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ACID-BASE ACID-BASE BALANCEBALANCE
H+ ion has special significance because of the narrow ranges that it must be maintained in order to be compatible with living systems
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ACID-BASE BALANCEACID-BASE BALANCE
Norm
al
Primarily controlled by regulation of H+ ions in the body fluidsEspecially
extracellular fluids
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ACID-BASE ACID-BASE REGULATIONREGULATION
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ACID-BASE REGULATIONACID-BASE REGULATIONMaintenance of an acceptable pH range in
the extracellular fluids is accomplished by three mechanisms:1)1) Chemical BuffersChemical Buffers
React very rapidly (less than a second)
2)2) Respiratory RegulationRespiratory RegulationReacts rapidly (seconds to minutes)
3)3) Renal RegulationRenal RegulationReacts slowly (minutes to hours)
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ACID-BASE REGULATIONACID-BASE REGULATIONChemical BuffersChemical Buffers
The body uses pH buffers in the blood to guard against sudden changes in acidity
A pH buffer works chemically to minimize changes in the pH of a solution
Buffer
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ACID-BASE REGULATIONACID-BASE REGULATIONRespiratory RegulationRespiratory Regulation
Carbon dioxide is an important by-product of metabolism and is constantly produced by cells
The blood carries carbon dioxide to the lungs where it is exhaled
CO2CO2 CO2
CO2CO2
CO2
Cell Metabolis
m
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ACID-BASE REGULATIONACID-BASE REGULATIONRespiratory RegulationRespiratory Regulation
When breathing is increased, the blood carbon dioxide level decreases and the blood becomes more basic
When breathing is decreased, the blood carbon dioxide level increases and the blood becomes more acidic
By adjusting the speed and depth of breathing, the respiratory control centers and lungs are able to regulate the blood pH minute by minute
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ACID-BASE REGULATIONACID-BASE REGULATIONKidney RegulationKidney Regulation
Excess acid is excreted by the kidneys, largely in the form of ammonia
The kidneys have some ability to alter the amount of acid or base that is excreted, but this generally takes several days
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ACID-BASE REGULATIONACID-BASE REGULATIONEnzymes, hormones and ion
distribution are all affected by hydrogen ion concentrations
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ACIDSACIDS
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ACIDSACIDSAcids can be defined as a proton (HH++) donor Hydrogen containing substances which
dissociate in solution to release HH++
Click Here
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ACIDSACIDSAcids can be defined as a proton (HH++) donor Hydrogen containing substances which
dissociate in solution to release HH++
Click Here
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ACIDSACIDSAcids can be defined as a proton (HH++) donor Hydrogen containing substances which
dissociate in solution to release HH++
H+OH-
H+
OH-
H+
OH-
H+
OH-
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ACIDSACIDSMany other substance (carbohydrates)
also contain hydrogen but they are not classified as acids because the hydrogen is tightly bound within their molecular structure and it is never liberated as free HH++
H+OH-
H+
OH-
H+
OH-
H+
OH-
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ACIDSACIDSPhysiologically important acids include:
Carbonic acid (HCarbonic acid (H22COCO33))Phosphoric acid (HPhosphoric acid (H33POPO44))Pyruvic acid (CPyruvic acid (C33HH44OO33))Lactic acid (CLactic acid (C33HH66OO33))
These acids are dissolved in body fluids
Lactic acidPyruvic acid
Phosphoric acid
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BASESBASES
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BASESBASESBases can be defined as:
A proton (HH++) acceptorMolecules capable of accepting a
hydrogen ion (OHOH--)
Click Here
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BASESBASESBases can be defined as:
A proton (HH++) acceptorMolecules capable of accepting a
hydrogen ion (OHOH--)
Click Here
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BASESBASESBases can be defined as:
A proton (HH++) acceptorMolecules capable of accepting a
hydrogen ion (OHOH--)
H+OH-
H+
OH-
H+
OH-
H+
OH-
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BASESBASES
Physiologically important bases include:Bicarbonate (HCOBicarbonate (HCO33
- - ))Biphosphate (HPOBiphosphate (HPO44
-2 -2 ))
Biphosphate
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pH SCALEpH SCALE
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pH refers to PPotential HHydrogenExpresses hydrogen ion concentration in
water solutionsWater ionizes to a limited extent to form
equal amounts of HH++ ions and OHOH-- ions
HH22OO HH++ + OH + OH--
HH++ ion is an acid
OHOH-- ion is a base
pH SCALEpH SCALE
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H+ ion is an acid
pH SCALEpH SCALE
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OH- ion is a base
pH SCALEpH SCALE
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H+ ion is an acid
OH- ion is a base
pH SCALEpH SCALE
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Pure water is NeutralNeutral ( H+ = OH- )
pH = 7AcidAcid
( H+ > OH- ) pH < 7
BaseBase ( H+ < OH- )
pH > 7Normal blood pH is 7.35 - 7.457.35 - 7.45pH range compatible with life is 6.8 - 8.06.8 - 8.0
pH SCALEpH SCALE
OH-
OH-
OH-
OH-
OH-
OH-
H+
H+
H+
H+
OH-
OH-
OH-
OH-OH-
H+
H+
H+H+
OH-OH-
OH-
H+
H+
H+
H+H+
H+
H+
ACIDS, BASES OR NEUTRAL???ACIDS, BASES OR NEUTRAL???
1
2
3
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pH SCALEpH SCALE
pH equals the logarithm (log) to the base 10 of the reciprocal of the hydrogen ion (HH++) concentration
HH++ concentration in extracellular fluid (ECF)
pH = log 1 / HH++ concentration
4 X 10 -8 (0.00000004)
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pH SCALEpH SCALE
Low pH values = high HH++ concentrationsHH++ concentration in denominator of
formula
Unit changes in pH represent a tenfold change in HH++ concentrationsNature of logarithms
pH = log 1 / HH++ concentration
4 X 10 -8 (0.00000004)
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pH SCALEpH SCALE
pH = 4 is more acidic than pH = 6pH = 4 has 10 times more free HH++
concentration than pH = 5 and 100 times more free HH++ concentration than pH = 6
ACIDOSIS ALKALOSISNORMAL
DEATH DEATH
Venous
Blood
Arterial Blood
7.3 7.57.46.8 8.0
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pH SCALEpH SCALE
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pH SCALEpH SCALE
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ACIDOSIS / ACIDOSIS / ALKALOSISALKALOSIS
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ACIDOSIS / ALKALOSISACIDOSIS / ALKALOSIS
An abnormality in one or more of the pH control mechanisms can cause one of two major disturbances in acid-base balanceAcidosisAcidosisAlkalosisAlkalosis
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ACIDOSIS / ALKALOSISACIDOSIS / ALKALOSIS
AcidosisAcidosisA condition in which the blood has too
much acid (or too little base), frequently resulting in a decrease in blood pH
AlkalosisAlkalosisA condition in which the blood has too
much base (or too little acid), occasionally resulting in an increase in blood pH
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ACIDOSIS / ALKALOSISACIDOSIS / ALKALOSISAcidosis and alkalosis are not diseases
but rather are the results of a wide variety of disorders
The presence ofacidosis oralkalosis providesan important clueto physicians thata seriousmetabolicproblem exists
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ACIDOSIS / ALKALOSISACIDOSIS / ALKALOSISpH changes have dramatic effects on
normal cell function1)1) Changes in excitability of nerve
and muscle cells2)2) Influences enzyme activity3)3) Influences KK++ levels
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CHANGES IN CELL CHANGES IN CELL EXCITABILITYEXCITABILITY
pH decrease (more acidic) depresses the central nervous systemCan lead to loss of consciousness
pH increase (more basic) can cause over-excitabilityTingling sensations, nervousness,
muscle twitches
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INFLUENCES ON ENZYME INFLUENCES ON ENZYME ACTIVITYACTIVITY
pH increases or decreases can alter the shape of the enzyme rendering it non-functional
Changes in enzyme structure can result in accelerated or depressed metabolic actions within the cell
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INFLUENCES ON KINFLUENCES ON K++ LEVELS LEVELS
When reabsorbing NaNa++ from the filtrate of the renal tubules KK++ or HH++ is secreted (exchanged)
Normally KK++ issecreted in muchgreater amountsthan HH++
K+
K+K+K+K+K+K+Na+Na+Na+Na+Na+Na+
H+
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INFLUENCES ON KINFLUENCES ON K++ LEVELS LEVELS
If HH++ concentrations are high (acidosis) than HH++ is secreted in greater amounts
This leaves less KK++ than usual excretedThe resultant KK++ retention can affect
cardiac function and other systems
K+K+K+Na+Na+Na+Na+Na+Na+
H+H+H+H+H+H+H+
K+K+K+K+K+
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A relative increase in hydrogen ions results in acidosis acidosis
ACIDOSISACIDOSIS
H+ OH-
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A relative increase in bicarbonate results in alkalosisalkalosis
ALKALOSISALKALOSIS
H+ OH-
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AlkalosisAlkalosis
ACIDOSIS / ALKALOSISACIDOSIS / ALKALOSIS
H+ OH-
AcidosisAcidosis
H+ OH-
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Normal ratio of HCOHCO33-- to HH22COCO33 is 20:1
HH22COCO33 is source of HH++ ions in the body
Deviations from this ratio are used to identify acid-base imbalances
ACIDOSIS / ALKALOSISACIDOSIS / ALKALOSISBASE ACID
H2CO
3
H+
HCO3-
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ACIDOSIS / ALKALOSISACIDOSIS / ALKALOSISAcidosisAcidosis and AlkalosisAlkalosis can arise in two
fundamentally different ways:
1) Excess or deficit of CO1) Excess or deficit of CO22
((Volatile AcidVolatile Acid))Volatile Acid Volatile Acid can be eliminated by the respiratory system
2) Excess or deficit of 2) Excess or deficit of Fixed AcidFixed AcidFixed AcidsFixed Acids cannot beeliminated by therespiratory system
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ACIDOSIS / ALKALOSISACIDOSIS / ALKALOSISNormal values of bicarbonate
(arterial)pH pH = 7.4
PCOPCO22 = 40 mm Hg
HCOHCO33-- = 24 meq/L
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ACIDOSISACIDOSISA decrease in the normal 20:1 base to acid ratioAn increase in the number of hydrogen
ions (ex: ratio of 20:2 translated to 10:1)A decrease in the number of bicarbonate
ions (ex: ratio of 10:1)Caused by too much acid or too little base
ACID
BASE
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ALKALOSISALKALOSISAn increase in the normal 20:1 base to
acid ratioA decrease in the number of hydrogen
ions (ex: ratio of 20:0.5 translated to 40:1)
An increase in the number of bicarbonate ions (ex: ratio of 40:1)
Caused by base excess or acid deficit
ACID
BASE
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SOURCES OF SOURCES OF HYDROGEN IONS HYDROGEN IONS
C C C C C C
H H H H H H
HHHHHH
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SOURCES OF HYDROGEN SOURCES OF HYDROGEN IONS IONS 1) Cell Metabolism (CO1) Cell Metabolism (CO22))
2) Food products2) Food products3) Medications3) Medications4) Metabolic intermediate by-4) Metabolic intermediate by-
productsproducts5) Some disease processes5) Some disease processes
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SOURCES OF HYDROGEN SOURCES OF HYDROGEN IONSIONS1) Cellular Metabolism1) Cellular Metabolism of
carbohydrates release COCO22 as a waste productAerobic respiration
CC66HH1212OO66 CO CO22 + H + H22O + EnergyO + Energy
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SOURCES OF HYDROGEN SOURCES OF HYDROGEN IONSIONSCOCO22 diffuses into the bloodstream
where the reaction: COCO2 2 + + HH22O HO H22COCO33 H H++ + HCO + HCO33
--
Occurs in red blood cells
HH22COCO33 (carbonic acid)
Acids produced as a result of the presence of COCO22 isreferred to as aVolatile acidVolatile acid
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SOURCES OF HYDROGEN SOURCES OF HYDROGEN IONSIONS
Dissociation of HH22COCO33 results in the production of free HH++ and HCOHCO33
--
The respiratory system removes COCO22 thus freeing HCOHCO33
-- to recombine with HH++
Accumulation or deficit of COCO22 in blood leads to respective HH++ accumulations or deficits
CO2 H+
CO2 H+
pH
pH
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CARBON DIOXIDE DIFFUSIONCARBON DIOXIDE DIFFUSION
COCO22
COCO22
Red Blood CellRed Blood CellSystemic Systemic CirculationCirculation
COCO22 HH22OO HH++ HCOHCO33--++ ++
HCOHCO33--
ClCl--
(Chloride (Chloride Shift)Shift)
COCO22 diffuses into plasma and into RBC diffuses into plasma and into RBC Within RBC, the hydration of COWithin RBC, the hydration of CO22 is is catalyzed by carbonic anhydrasecatalyzed by carbonic anhydraseBicarbonate thus formed diffuses into Bicarbonate thus formed diffuses into plasmaplasma
carboniccarbonicanhydraseanhydrase
TissuesTissues
PlasmaPlasma
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CARBON DIOXIDE DIFFUSIONCARBON DIOXIDE DIFFUSION
COCO22
Red Blood CellRed Blood CellSystemic CirculationSystemic Circulation
HH22OO
HH++ HCOHCO33--
carboniccarbonicanhydraseanhydrase
PlasmaPlasma
COCO22 COCO22COCO22 COCO22 COCO22 COCO22
COCO22
Click for Carbon Dioxide diffusion
++ ++
TissuesTissues
HH++
ClCl--
HbHbHH++ is buffered is buffered
by Hemoglobinby Hemoglobin
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SOURCES OF HYDROGEN SOURCES OF HYDROGEN IONS IONS 2) Food products2) Food products
SauerkrautYogurtCitric acid in fruits
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SOURCES OF HYDROGEN SOURCES OF HYDROGEN IONS IONS
3) Medications3) MedicationsMay stimulate HClHCl production by parietal cells of the stomach
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SOURCES OF HYDROGEN SOURCES OF HYDROGEN IONS IONS
4) Metabolic 4) Metabolic intermediate intermediate by-productsby-productsLactic acidPyruvic acidAcetoacetic acid
Fatty acids
CC66HH1212OO66 2 2 CC33HH66OO33
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SOURCES OF HYDROGEN SOURCES OF HYDROGEN IONS IONS Inorganic acids can also be produced
during breakdown of nutrientsProteinsProteins (meat products)
breakdown leads toproductions of sulfuricacid and phosphoric acid
FruitsFruits and VegetablesVegetables breakdown produces bases whichcan help to equalizeacid production
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SOURCES OF HYDROGEN SOURCES OF HYDROGEN IONS IONS 5) Some disease processes5) Some disease processes
Ex: diabetes causes improper metabolism of fats which results in the generation of a waste product called a Keto AcidKeto Acid
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SOURCES OF SOURCES OF BICARBONATE IONSBICARBONATE IONS
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SOURCES OF BICARBONATE SOURCES OF BICARBONATE IONSIONS
1) CO1) CO22 diffusion into red blood cells diffusion into red blood cells
2) Parietal cell2) Parietal cellsecretion of thesecretion of thegastric mucosagastric mucosa
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1) CO1) CO2 2 DIFFUSIONDIFFUSION
Hemoglobin buffers H+
Chloride shift insures electrical neutrality
Hb
Cl-
H+
H+
H+
H+
H+
H+
H+
H+
Cl-
Cl-Cl-
Cl-
Cl-
Cl-
Cl-
Red Blood Cell
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CARBON DIOXIDE DIFFUSIONCARBON DIOXIDE DIFFUSION
COCO22
COCO22
Red Blood CellRed Blood Cell Systemic CirculationSystemic Circulation
COCO22 HH22OO HH++ HCOHCO33--++ ++
HCOHCO33--
ClCl--
(Chloride (Chloride Shift)Shift)
COCO22 diffuses into plasma and into RBC diffuses into plasma and into RBC
Within RBC, the hydration of COWithin RBC, the hydration of CO22 is is
catalyzed by carbonic anhydrasecatalyzed by carbonic anhydraseBicarbonate thus formed diffuses into Bicarbonate thus formed diffuses into plasmaplasma
carboniccarbonicanhydraseanhydrase
TissuesTissues
PlasmaPlasma
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BICARBONATE DIFFUSIONBICARBONATE DIFFUSION
Red Blood CellRed Blood Cell Pulmonary CirculationPulmonary Circulation
COCO22 HH22OO HH++ HCOHCO33--++ ++
HCOHCO33--
ClCl--
AlveolusAlveolus
PlasmaPlasma
COCO22Bicarbonate diffuses back into RBC Bicarbonate diffuses back into RBC in pulmonary capillaries and reacts in pulmonary capillaries and reacts with hydrogen ions to form carbonic with hydrogen ions to form carbonic acidacid
The acid breaks down to COThe acid breaks down to CO2 2 and and waterwater
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BICARBONATE DIFFUSIONBICARBONATE DIFFUSION
Red Blood CellRed Blood Cell Pulmonary CirculationPulmonary Circulation
COCO22 HH22OO
HH++
++ ++ HCOHCO33--
ClCl--
AlveolusAlveolus
PlasmaPlasma
COCO22
COCO22 HH22OO
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2) PARIETAL CELL 2) PARIETAL CELL SECRETIONSECRETION
Bicarbonate ions diffuse into the bloodstream to maintain electrical neutrality in the parietal cell
Blood
Lumen of
Stomach
Parietal Cells
H+Cl-
HCO3-
HCl
Click to see ion
movement
CO2 + H2O
Secrete hydrogen ions into the lumen of the stomach
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PARIETAL CELL SECRETIONPARIETAL CELL SECRETION
Blood
Pancreatic
duct
Pancreatic Cells
H+
HCO3-
Click to see ion
movement
H+ ions are secreted into the blood and bicarbonate ions diffuse into pancreatic juice
In pancreatic epithelial cells the direction of ion movement is reversed
HCO3-
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PARIETAL CELL SECRETIONPARIETAL CELL SECRETIONIf the two processes are balanced,
there is no net change in the amount of bicarbonate in bloodLoss of gastric or pancreatic juice
can change that balance
HCO3-
HCO3-
HCO3-
HCO3-
HCO3-
HCO3-
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Cells of the gastric mucosa secrete H+ ions into the lumen of the stomach in exchange for the diffusion of bicarbonate ions into blood
The direction of the diffusion of these ions is reversed in pancreatic epithelial cells
BICARBONATE SECRETIONBICARBONATE SECRETIONParietal cells of gastric mucosa
Pancreaticepithelial cells
HCO3-
H+
HCO3-
H+
lumen ofstomach
pancreaticjuice
blood
blood
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ACIDOSIS / ACIDOSIS / ALKALOSISALKALOSIS
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ACIDOSIS / ALKALOSISACIDOSIS / ALKALOSISDeviations from normal acid-base
status are divided into four general categories, depending on the source and direction of the abnormal change in HH++ concentrationsRespiratory AcidosisRespiratory AcidosisRespiratory AlkalosisRespiratory AlkalosisMetabolic AcidosisMetabolic AcidosisMetabolic AlkalosisMetabolic Alkalosis
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ACIDOSIS / ALKALOSISACIDOSIS / ALKALOSISAcidosis and Alkalosis are categorized as
MetabolicMetabolic or RespiratoryRespiratory depending on their primary causeMetabolic Acidosis and Metabolic Metabolic
AlkalosisAlkalosis are caused by an imbalance in the production and excretion of acids or bases by the kidneys
RespiratoryRespiratory AcidosisAcidosis and Respiratory AlkalosisRespiratory Alkalosis are caused primarily by lung or breathing disorders
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ACIDOSISACIDOSISA pH of 7.4 corresponds to a 20:1
ratio of HCO3- and H2CO3
Concentration of HCO3- is 24
meq/liter and H2CO3 is 1.2 meq/literBicarbonate
Carbonic Acid
BicarbonateBicarbonat
eBicarbonateBicarbonat
eBicarbonateBicarbonateBicarbonat
e
BicarbonateBicarbonateBicarbonat
eBicarbonate Bicarbonat
eBicarbonateBicarbonate
BicarbonateBicarbonat
e
BicarbonateBicarbonat
e Bicarbonate
7.4
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ACIDOSISACIDOSISAcidosis is a decreasedecrease in pH below 7.35
Which means a relative increase of H+ ions
pH may fall as low as 7.0 without irreversible damage but any fall less than 7.0 is usually fatal
H+ pH
=
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ACIDOSIS ACIDOSIS May be caused by:
An increase in H2CO3
A decrease in HCO3-
Both lead to a decrease in the ratio of 20:1
H2CO3 HCO3-
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ACIDOSISACIDOSIS
1) Respiratory Acidosis2) Metabolic Acidosis
H+
H+
H+
H+
H+H+
H+
H+
H+
H+
H+
H+
H+
H+
H+H+
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H+
H+
H+
H+
H+H+
H+
H+
H+
H+
H+
H+
H+
H+
H+
H+
1) Respiratory alkalosis2) Metabolic alkalosis
ALKALOSISALKALOSIS
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RESPIRATORY RESPIRATORY ACIDOSISACIDOSIS
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RESPIRATORY ACIDOSISRESPIRATORY ACIDOSISCaused by hyperkapnia due to
hypoventilationCharacterized by a pH decrease
and an increase in COCO22
CO2 CO2
CO2
CO2
CO2
CO2CO2
CO2CO2
CO2
CO2 CO2
CO2
pH
pH
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HYPOVENTILATIONHYPOVENTILATION
Hypo = “Under”
Elimination of CO2
H+
pH
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RESPIRATORY ACIDOSISRESPIRATORY ACIDOSISHyperkapniaHyperkapnia is defined as an
accumulation of carbon dioxide in extracellular fluids
CO2 CO2
CO2
CO2
CO2
CO2CO2
CO2CO2
CO2
CO2 CO2
CO2
pH
pH
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RESPIRATORY ACIDOSISRESPIRATORY ACIDOSIS
Hyperkapnia is the underlying cause of Respiratory AcidosisRespiratory Acidosis
Usually the result of decreased COCO22 removal from the lungs
CO2 CO2
CO2
CO2
CO2
CO2CO2
CO2CO2
CO2
CO2 CO2
CO2
pH
pH
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RESPIRATORY ACIDOSISRESPIRATORY ACIDOSISThe speed and depth of breathing control
the amount of COCO22 in the blood
Normally when COCO22 builds up, the pHpH of the blood falls and the blood becomes acidic
High levels of COCO22 in the blood stimulate the parts of the brain that regulate breathing, which in turn stimulate faster and deeper breathing
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RESPIRATORY ACIDOSISRESPIRATORY ACIDOSIS
Respiratory acidosis develops when the lungs don't expel COCO22 adequately
This can happen in diseases that severely affect the lungs, such as emphysema, chronic bronchitis, severe pneumonia, pulmonary edema, and asthma
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RESPIRATORY ACIDOSISRESPIRATORY ACIDOSISRespiratory acidosis can also develop when
diseases of the nerves or muscles of the chest impair the mechanics of breathing
In addition, a person can develop respiratory acidosis if overly sedated from narcotics and strong sleeping medications that slow respiration
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RESPIRATORY ACIDOSISRESPIRATORY ACIDOSISThe treatment of respiratory acidosis
aims to improve the function of the lungsDrugs to improve breathing may help
people who have lung diseases such as asthma and emphysema
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RESPIRATORY ACIDOSISRESPIRATORY ACIDOSIS Decreased COCO22 removal
can be the result of:1)1)Obstruction of air Obstruction of air
passagespassages2)2)Decreased respiration Decreased respiration
(depression of (depression of respiratory centers)respiratory centers)
3)3)Decreased gas Decreased gas exchange between exchange between pulmonary capillaries pulmonary capillaries and air sacs of lungsand air sacs of lungs
4)4)Collapse of lungCollapse of lung
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RESPIRATORY ACIDOSISRESPIRATORY ACIDOSIS1) Obstruction of air passages1) Obstruction of air passages
Vomit, anaphylaxis, tracheal cancer
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RESPIRATORY ACIDOSISRESPIRATORY ACIDOSIS2) Decreased Respiration2) Decreased Respiration
Shallow, slow breathing Depression of the respiratory centers in
the brain which control breathing ratesDrug overdose
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RESPIRATORY ACIDOSISRESPIRATORY ACIDOSIS3) Decreased 3) Decreased
gas exchange gas exchange between between pulmonary pulmonary capillaries and capillaries and air sacs of air sacs of lungslungsEmphysemaBronchitisPulmonary
edema
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RESPIRATORY ACIDOSISRESPIRATORY ACIDOSIS4) Collapse of lung4) Collapse of lung
Compression injury, open thoracic Compression injury, open thoracic woundwound
Left lung collapsed
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RESPIRATORY ACIDOSISRESPIRATORY ACIDOSIS-metabolic balance before onset of acidosis-pH = 7.4
-respiratory acidosis-pH = 7.1-breathing is suppressed holding CO2 in body
-body’s compensation-kidneys conserve HCO3
- ions to restore the normal 40:2 ratio-kidneys eliminate H+ ion in acidic urine- therapy required to restore metabolic balance
- lactate solution used in therapy is converted to bicarbonate ions in the liver
40
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RESPIRATORY ACIDOSISRESPIRATORY ACIDOSIS
- metabolic balance before onset of acidosis- pH = 7.4
H2CO
3
HCO3-
1 20:
H2CO3 : Carbonic Acid
HCO3- : Bicarbonate Ion
(Na+) HCO3-
(K+) HCO3-
(Mg++) HCO3-
(Ca++) HCO3-
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RESPIRATORY ACIDOSISRESPIRATORY ACIDOSIS
-breathing is suppressed holding CO2 in body-pH = 7.1
H2CO
3
HCO3-
2 20:
CO2 CO
2
CO2
CO2
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RESPIRATORY ACIDOSISRESPIRATORY ACIDOSIS
-body’s compensation-kidneys conserve HCO3
- ions to restore the normal 40:2 ratio-kidneys eliminate H+ ion in acidic urine
H2CO
3
HCO3-
2 30:
HCO3-
H2CO
3
HCO3-
H+
+
acidic urine
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RESPIRATORY ACIDOSISRESPIRATORY ACIDOSIS
- therapy required to restore metabolic balance
- lactate solution used in therapy is converted to bicarbonate ions in the liver
H2CO
3
HCO3-
2 40:
Lactate
Lactate
LIVER
HCO3-
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RESPIRATORY RESPIRATORY ALKALOSISALKALOSIS
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RESPIRATORY ALKALOSISRESPIRATORY ALKALOSIS
Normal 20:1 ratio is increasedpH of blood is above 7.4
H2CO
3
HCO3-
1 20:=7.4
H2CO
3HCO
3-
0.5
20:= 7.4
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RESPIRATORY ALKALOSISRESPIRATORY ALKALOSIS
Cause is HyperventilationLeads to eliminating excessive
amounts of COCO22
Increased loss of COCO22 from the lungs at a rate faster than it is produced
Decrease in HH++
CO2
CO2
CO2
CO2
CO2 CO
2
CO2
CO2
CO2
CO2
CO2
CO2
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HYPERVENTILATIONHYPERVENTILATION
Hyper = “Over”
Elimination of CO2
H+
pH
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RESPIRATORY ALKALOSISRESPIRATORY ALKALOSISCan be the result of:
1) Anxiety, emotional disturbances
2) Respiratory center lesions
3) Fever4) Salicylate poisoning
(overdose)5) Assisted respiration6) High altitude (low
PO2)
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RESPIRATORY ALKALOSISRESPIRATORY ALKALOSISAnxiety is an emotional
disturbanceThe most common cause
of hyperventilation, and thus respiratory alkalosis, is anxiety
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RESPIRATORY ALKALOSISRESPIRATORY ALKALOSISUsually the only treatment needed is
to slow down the rate of breathingBreathing into a paper bag or holding
the breath as long as possible may help raise the blood COCO22 content as the person breathes carbon dioxideback in after breathing it out
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RESPIRATORY ALKALOSISRESPIRATORY ALKALOSISRespiratory center Respiratory center
lesionslesionsDamage to brain Damage to brain
centers responsible centers responsible for monitoring for monitoring breathing ratesbreathing ratesTumorsTumorsStrokesStrokes
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RESPIRATORY ALKALOSISRESPIRATORY ALKALOSISFFeverever
Rapid shallow Rapid shallow breathing blows off breathing blows off too much too much COCO22
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RESPIRATORY ALKALOSISRESPIRATORY ALKALOSISSalicylate poisoning Salicylate poisoning
(Aspirin overdose)(Aspirin overdose)Ventilation is Ventilation is
stimulated without stimulated without regard to the status of regard to the status of OO22, , COCO22 or or HH++ in the in the body fluidsbody fluids
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RESPIRATORY ALKALOSISRESPIRATORY ALKALOSISAssisted RespirationAssisted Respiration
Administration of Administration of COCO22 in the exhaled in the exhaled air of the care - giverair of the care - giver
Your insurance won’t cover a ventilator any longer, so Bob here will be giving you mouth to mouth for the next several days
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RESPIRATORY ALKALOSISRESPIRATORY ALKALOSISHigh AltitudeHigh Altitude
Low concentrations of Low concentrations of OO2 2 in the arterial in the arterial blood reflexly stimulates ventilation in blood reflexly stimulates ventilation in an attempt to obtain morean attempt to obtain more O O22
Too much Too much COCO22 is “blown off” in the is “blown off” in the processprocess
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RESPIRATORY ALKALOSISRESPIRATORY ALKALOSISKidneys compensate by:
Retaining hydrogen ionsRetaining hydrogen ionsIncreasing bicarbonate excretionIncreasing bicarbonate excretion
H+
HCO3-
HCO3-
HCO3-
HCO3-
HCO3-
HCO3-
HCO3-
HCO3-
HCO3-
HCO3-
H+
H+
H+
H+
H+
H+
H+
H+
H+
H+
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RESPIRATORY ALKALOSISRESPIRATORY ALKALOSISDecreased COCO22 in the lungs will
eventually slow the rate of breathingWill permit a normal amount of
COCO22 to be retained in the lung
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RESPIRATORY ALKALOSISRESPIRATORY ALKALOSIS-metabolic balance before onset of alkalosis-pH = 7.4
-respiratory alkalosis-pH = 7.7
- hyperactive breathing “ blows off ” CO2
- body’s compensation
- kidneys conserve H+ ions and eliminate HCO3
- in alkaline urine
- therapy required to restore metabolic balance
- HCO3- ions replaced by Cl- ions
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RESPIRATORY ALKALOSISRESPIRATORY ALKALOSIS
-metabolic balance before onset of alkalosis-pH = 7.4
H2CO
3
HCO3-
1 20:
H2CO3 : Carbonic Acid
HCO3- : Bicarbonate Ion
(Na+) HCO3-
(K+) HCO3-
(Mg++) HCO3-
(Ca++) HCO3-
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RESPIRATORY ALKALOSISRESPIRATORY ALKALOSIS
-respiratory alkalosis-pH = 7.7-hyperactive breathing “ blows off ” CO2
H2CO
3 HCO3
-
0.5 20:
CO2
CO2 + H2O
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RESPIRATORY ALKALOSISRESPIRATORY ALKALOSIS
- body’s compensation- kidneys conserve H+ ions and eliminate HCO3
- in alkaline urine
H2CO
3
HCO3
-
0.5 15:
HCO3-
Alkaline Urine
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RESPIRATORY ALKALOSISRESPIRATORY ALKALOSIS
- therapy required to restore metabolic balance
- HCO3- ions replaced by Cl- ions
H2CO
3
HCO3-
0.5 10:
Cl-
Chloride containing solution
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RESPIRATORYRESPIRATORYACIDOSIS / ALKALOSISACIDOSIS / ALKALOSIS
COCO22 + H + H22OO HH22COCO33 HH++ + + HCOHCO33
--
Respiratory Acidosis
Respiratory Alkalosis
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METABOLIC ACIDOSISMETABOLIC ACIDOSIS
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METABOLIC ACIDOSISMETABOLIC ACIDOSISOccurs when there is a decrease in
the normal 20:1 ratioDecrease in blood pHpH and
bicarbonate level
Excessive HH++ or decreased HCOHCO33--
H2CO
3
HCO3-
1 20:= 7.4
H2CO
3
HCO3-
1 10:= 7.4
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METABOLIC ACIDOSISMETABOLIC ACIDOSISAny acid-base
imbalance not attributable to COCO22 is classified as metabolicMetabolic
production of AcidsAcids
Or loss of BasesBases
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METABOLIC ACIDOSISMETABOLIC ACIDOSISIf an increase in acid overwhelms the
body's pHpH buffering system, the blood can become acidic
As the blood pHpH drops,breathing becomesdeeper and faster as thebody attempts to rid theblood of excess acid bydecreasing the amount ofcarbon dioxide
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METABOLIC ACIDOSISMETABOLIC ACIDOSISEventually, the kidneys
also try to compensate by excreting more acid in the urine
However, both mechanisms can be overwhelmed if the body continues to produce too much acid, leading to severe acidosis and eventually a coma
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METABOLIC ACIDOSISMETABOLIC ACIDOSISMetabolic acidosis is always
characterized by a reduction in plasma HCOHCO33
-- while COCO22 remains normal
HCO3-
CO2
Plasma Levels
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METABOLIC ACIDOSISMETABOLIC ACIDOSISAcidosis results from excessive loss of
HCOHCO33-- rich fluids from the body or from an
accumulation of acidsAccumulation of non-carbonic plasma
acids uses HCOHCO33-- as a buffer for the
additional HH++ thus reducing HCOHCO33-- levels
Lactic Acid
Muscle Cell
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METABOLIC ACIDOSISMETABOLIC ACIDOSISThe causes of metabolic acidosis can
be grouped into fivefive major categories1)1) Ingesting an acid or a substance
that is metabolized to acid2) Abnormal Metabolism2) Abnormal Metabolism3) Kidney Insufficiencies3) Kidney Insufficiencies4) Strenuous Exercise4) Strenuous Exercise5) Severe Diarrhea5) Severe Diarrhea
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METABOLIC ACIDOSISMETABOLIC ACIDOSIS1) Ingesting An Acid1) Ingesting An Acid
Most substances that cause acidosis when ingested are considered poisonous
Examples include wood alcohol (methanol) and antifreeze (ethylene glycol)
However, even an overdoseof aspirin (acetylsalicylic acid)can cause metabolic acidosis
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METABOLIC ACIDOSISMETABOLIC ACIDOSIS2) Abnormal Metabolism2) Abnormal Metabolism
The body can produce excess acid as a result of several diseasesOne of the most significant is Type I Diabetes Mellitus
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METABOLIC ACIDOSISMETABOLIC ACIDOSISUnregulated
diabetes mellitus causes ketoacidosisketoacidosisBody metabolizes
fat rather than glucose
Accumulations of metabolic acids (Keto Acids)(Keto Acids) cause an increase in plasma HH++
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METABOLIC ACIDOSISMETABOLIC ACIDOSISThis leads to excessive production of
ketones:ketones:AcetoneAcetoneAcetoacetic acidAcetoacetic acidB-hydroxybutyric acidB-hydroxybutyric acid
Contribute excessive numbers of hydrogen ions to body fluids
Acetone
Acetoacetic acid
Hydroxybutyric acid
H+
H+
H+
H+
H+H+H+
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METABOLIC ACIDOSISMETABOLIC ACIDOSIS2) Abnormal Metabolism2) Abnormal Metabolism
The body also produces excess acid in the advanced stages of shock, when lactic acid is formed through the metabolism of sugar
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METABOLIC ACIDOSISMETABOLIC ACIDOSIS
3) Kidney 3) Kidney InsufficienciesInsufficienciesEven the production
of normal amounts of acid may lead to acidosis when the kidneys aren't functioning normally
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METABOLIC ACIDOSISMETABOLIC ACIDOSIS3) Kidney Insufficiencies3) Kidney Insufficiencies
Kidneys may be unable to rid the plasma of even the normal amounts of HH++ generated from metabolic acids
Kidneys may be also unable to conserve an adequate amount of HCOHCO33
-- to buffer the normal acid load
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METABOLIC ACIDOSISMETABOLIC ACIDOSIS3) Kidney Insufficiencies3) Kidney Insufficiencies
This type of kidney malfunction is called renal tubular acidosisrenal tubular acidosis or uremic acidosisuremic acidosis and may occur in people with kidney failure or with abnormalities that affect the kidneys' ability to excrete acid
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METABOLIC ACIDOSISMETABOLIC ACIDOSIS
4) Strenuous Exercise4) Strenuous ExerciseMuscles resort to anaerobic glycolysis
during strenuous exerciseAnaerobic respiration leads to the
production of large amounts of lactic acid
C6H12O6 2C3H6O3 + ATP (energy)
Enzymes
Lactic Acid
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METABOLIC ACIDOSISMETABOLIC ACIDOSIS5) Severe Diarrhea5) Severe Diarrhea
Fluids rich in HCOHCO33-- are released and
reabsorbed during the digestive process
During diarrhea this HCOHCO33-- is lost from
the body rather than reabsorbed
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METABOLIC ACIDOSISMETABOLIC ACIDOSIS5) Severe Diarrhea5) Severe Diarrhea
The loss of HCOHCO33-- without a
corresponding loss of H+ lowers the pH
Less HCOHCO33-- is available for buffering HH++
Prolonged deep (from duodenum) vomiting can result in the same situation
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METABOLIC ACIDOSISMETABOLIC ACIDOSISTreating the underlying cause of
metabolic acidosis is the usual course of actionFor example, they may control diabetes
with insulin or treat poisoning by removing the toxic substancefrom the blood
Occasionallydialysis is neededto treat severeoverdoses andpoisonings
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METABOLIC ACIDOSISMETABOLIC ACIDOSIS
Metabolic acidosis may also be treated directlyIf the acidosis is mild,
intravenous fluids and treatment for the underlying disorder may be all that's needed
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METABOLIC ACIDOSISMETABOLIC ACIDOSIS
When acidosis is severe, bicarbonate may be given intravenouslyBicarbonate provides
only temporary relief and may cause harm
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METABOLIC ACIDOSISMETABOLIC ACIDOSIS
- metabolic balance before onset of acidosis- pH 7.4
- metabolic acidosis- pH 7.1
- HCO3- decreases because of
excess presence of ketones, chloride or organic ions
- body’s compensation- hyperactive breathing to “ blow off ” CO2
- kidneys conserve HCO3- and
eliminate H+ ions in acidic urine
- therapy required to restore metabolic balance
- lactate solution used in therapy isconverted to bicarbonate ionsin the liver
0.5 10
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METABOLIC ACIDOSISMETABOLIC ACIDOSIS
-metabolic balance before onset of acidosis-pH 7.4
H2CO3 : Carbonic Acid
HCO3- : Bicarbonate Ion
(Na+) HCO3-
(K+) HCO3-
(Mg++) HCO3-
(Ca++) HCO3-
H2CO
3
HCO3-
1 20:
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METABOLIC ACIDOSISMETABOLIC ACIDOSIS
-HCO3- decreases because of excess
presence of ketones, chloride or organic ions-pH 7.1
H2CO
3
HCO3-
1 10:= 7.4
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METABOLIC ACIDOSISMETABOLIC ACIDOSIS
- body’s compensation
- hyperactive breathing to “ blow off ” CO2- kidneys conserve HCO3
- and eliminate H+ ions in acidic urine
H2CO
3
HCO3-
0.75 10:
CO2
COCO22 + + HH22OO
HCO3- +
H+
HCOHCO33--
++
HH++
Acidic urine
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METABOLIC ACIDOSISMETABOLIC ACIDOSIS
- therapy required to restore metabolic balance- lactate solution used in therapy is converted to bicarbonate ions in the liver
H2CO
3
HCO3-
0.5 10:
Lactate
Lactate containing solution
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METABOLIC ALKALOSISMETABOLIC ALKALOSIS
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METABOLIC ALKALOSISMETABOLIC ALKALOSISElevation of pHpH due to an increased 20:1
ratioMay be caused by:
An increase of bicarbonate A decrease in hydrogen ions
Imbalance again cannot be due to COCO22
Increase in pHpH which has a non-respiratory origin
7.4
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METABOLIC ALKALOSISMETABOLIC ALKALOSISA reduction in HH++ in the case of metabolic
alkalosis can be caused by a deficiency of non-carbonic acids
This is associated with an increase in HCOHCO33--
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METABOLIC ALKALOSISMETABOLIC ALKALOSISTreatment of metabolic alkalosis is most
often accomplished by replacing water and electrolytes (sodiumsodium and potassiumpotassium) while treating the underlying cause
Occasionally when metabolic alkalosis is very severe, dilute acid in the form of ammonium chloride is given intravenously
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METABOLIC ALKALOSISMETABOLIC ALKALOSISCan be the result of:
1) Ingestion of Alkaline 1) Ingestion of Alkaline SubstancesSubstances
2) Vomiting ( loss of HCl )2) Vomiting ( loss of HCl )
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METABOLIC ALKALOSISMETABOLIC ALKALOSIS1) Ingestion of Alkaline Substances1) Ingestion of Alkaline Substances
Influx of NaHCONaHCO33
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METABOLIC ALKALOSISMETABOLIC ALKALOSISBaking soda (NaHCONaHCO33) often used as a
remedy for gastric hyperacidity
NaHCONaHCO33 dissociates to NaNa++ and HCOHCO33--
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METABOLIC ALKALOSISMETABOLIC ALKALOSISBicarbonate neutralizes high
acidity in stomach (heart burn)
The extra bicarbonate is absorbed into the plasma increasing pHpH of plasma as bicarbonate binds with free HH++
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METABOLIC ALKALOSISMETABOLIC ALKALOSISCommercially prepared alkaline products
for gastric hyperacidity are not absorbed from the digestive tract and do not alter the pHpH status of the plasma
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METABOLIC ALKALOSISMETABOLIC ALKALOSIS2) Vomiting (abnormal loss of HCl)2) Vomiting (abnormal loss of HCl)Excessive loss of H+
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METABOLIC ALKALOSISMETABOLIC ALKALOSISGastric juices contain large amounts of
HClHClDuring HClHCl secretion, bicarbonate is added
to the plasma
K+ H+
Cl-
HCO3-
HCl
Click toView Animation
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HCl
METABOLIC ALKALOSISMETABOLIC ALKALOSIS
K+
H+ Cl-
HCO3-
Click toView Animation
The bicarbonate is neutralized as HClHCl is reabsorbed by the plasma from the digestive tract
H2CO
3
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METABOLIC ALKALOSISMETABOLIC ALKALOSIS
HCl K+
HCO3-
Click toView Animation
During vomiting HH++ is lost as HClHCl and the bicarbonate is not neutralized in the plasmaLoss of HClHCl increases the plasma
bicarbonate and thus results in an increase in pHpH of the blood
Bicarbonate not Bicarbonate not neutralizedneutralized
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METABOLIC ALKALOSIS METABOLIC ALKALOSIS Reaction of the body to alkalosis is to
lower pHpH by:Retain CO2 by decreasing breathing
rateKidneys increase the retention of HH++
CO2 CO2
H+
H+
H+
H+
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METABOLIC ALKALOSISMETABOLIC ALKALOSIS
- metabolic balance before onset of alkalosis- pH = 7.4
- metabolic alkalosis- pH = 7.7
- HCO3- increases because of loss
of chloride ions or excess ingestion of NaHCO3
- body’s compensation- breathing suppressed to hold CO2- kidneys conserve H+ ions and eliminate HCO3
- in alkaline urine
- therapy required to restore metabolic balance
- HCO3- ions replaced by Cl- ions1.2
525
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METABOLIC ALKALOSISMETABOLIC ALKALOSIS
- metabolic balance before onset of alkalosis- pH = 7.4
H2CO3 : Carbonic Acid
HCO3- : Bicarbonate Ion
(Na+) HCO3-
(K+) HCO3-
(Mg++) HCO3-
(Ca++) HCO3-
H2CO
3
HCO3-
1 20:
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METABOLIC ALKALOSISMETABOLIC ALKALOSIS
- pH = 7.7- HCO3
- increases because of loss of chloride ions or excess ingestion of NaHCO3
HCO3
-
1 40:
H2CO
3
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H2CO
3
HCO3-
METABOLIC ALKALOSISMETABOLIC ALKALOSIS
- body’s compensation
- breathing suppressed to hold CO2
- kidneys conserve H+ ions and eliminate HCO3
- in alkaline urine
1.25 30
CO2 + H2O
HCO3- +
H+
HCO3-
H+
+
Alkaline urine
:
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METABOLIC ALKALOSISMETABOLIC ALKALOSIS
- Therapy required to restore metabolic balance- HCO3
- ions replaced by Cl- ions
H2CO
3
HCO3-
1.25 25:
Cl-
Chloride containing solution
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ACIDOSISACIDOSIS
respiratoryacidosis
decreasedremoval ofCO2 from
lungs
failure of kidneys to
excreteacids
metabolicacid
productionof keto acids
absorption ofmetabolic acids
from GI tract
prolongeddiarrhea
accumulationof CO2 in blood
accumulationof acid in blood
excessive lossof NaHCO3 from blood
metabolicacidosis
deepvomiting
from GI tract
kidneydisease(uremia)
increase inplasma H+concentrati
on
depression ofnervous system
accumulationof CO2 in blood
accumulationof acid in blood
excessive lossof NaHCO3 from blood
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ALKALOSISALKALOSIS
respiratoryalkalosis
anxiety overdose of certain
drugs
high altitudes
prolongedvomiting
ingestion of excessive
alkaline drugs
excessaldosterone
hyperventilation
loss of CO2 and
H2CO2 from blood
loss of acid accumulationof base
metabolicalkalosis
decreasein plasmaH+
concentration
overexcitabilityof nervous
system
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ACID – BASE DISORDERSACID – BASE DISORDERS
Clinical State Acid-Base Disorder Pulmonary Embolus Respiratory Alkalosis
Shock Metabolic Acidosis
Vomiting Metabolic Alkalosis
Severe Diarrhea Metabolic Acidosis
Cirrhosis Respiratory Alkalosis
Renal Failure Metabolic Acidosis
Sepsis (Bloodstream Infection)Respiratory Alkalosis, Metabolic
Acidosis
Pregnancy Respiratory Alkalosis
Diuretic Use Metabolic Alkalosis
Chronic Obstructive Pulmonary Disease
Respiratory Acidosis
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RESPONSES TO ACIDOSIS RESPONSES TO ACIDOSIS AND ALKALOSISAND ALKALOSIS
Mechanisms protect the body against life-threatening changes in hydrogen ion concentration1) Buffering Systems in Body 1) Buffering Systems in Body FluidsFluids
2) Respiratory Responses2) Respiratory Responses3) Renal Responses3) Renal Responses4) Intracellular Shifts of Ions4) Intracellular Shifts of Ions
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1)1) Buffer SystemsBuffer Systems2) Respiratory Responses2) Respiratory Responses
3) Renal Responses3) Renal Responses4) Intracellular Shifts of Ions4) Intracellular Shifts of Ions
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BUFFERSBUFFERSBuffering systems provide an immediate
response to fluctuations in pHpH1) Phosphate1) Phosphate2) Protein2) Protein3) Bicarbonate Buffer System3) Bicarbonate Buffer System
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BUFFERSBUFFERSA buffer is a combination of chemicals
in solution that resists any significant change in pHpH
Able to bind or release free HH++ ions
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BUFFERSBUFFERSChemical buffers are able to react
immediately (within milliseconds)Chemical buffers are the first line of
defense for the body for fluctuations in pHpH
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1) Phosphate buffer system1) Phosphate buffer system
Na2HPO4 + H+ NaH2PO4 +
Na+ Most important in the intracellular
system
PHOSPHATE BUFFER SYSTEMPHOSPHATE BUFFER SYSTEM
H+ Na2HPO
4
+
NaH2PO
4
Click to animate
Na++
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Na2HPO4 + H+ NaH2PO4 + Na+
Alternately switches NaNa++ with HH++
PHOSPHATE BUFFER SYSTEMPHOSPHATE BUFFER SYSTEM
H+ Na2HPO
4
+
NaH2PO
4
Click to animate
Na++
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Na2HPO4 + H+ NaH2PO4 + Na+
Phosphates are more abundant within the cell and are rivaled as a buffer in the ICF by even more abundant protein
PHOSPHATE BUFFER SYSTEMPHOSPHATE BUFFER SYSTEM
Na2HPO
4 Na2HPO
4Na2HPO
4
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Regulates pHpH within the cells and the urinePhosphate concentrations are higher
intracellularly and within the kidney tubules
Too low of aconcentration inextracellular fluidto have muchimportance as anECFECF buffer system
PHOSPHATE BUFFER SYSTEMPHOSPHATE BUFFER SYSTEM
HPO4-
2
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PROTEIN BUFFER SYSTEMPROTEIN BUFFER SYSTEM2) Protein Buffer System2) Protein Buffer System
Behaves as a buffer in both plasma and cells
Hemoglobin is by far the most important protein buffer
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PROTEIN BUFFER SYSTEMPROTEIN BUFFER SYSTEM
Most important intracellular buffer (ICFICF)
The most plentiful buffer of the body
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PROTEIN BUFFER SYSTEMPROTEIN BUFFER SYSTEMProteins are excellent buffers because
they contain both acid and base groups that can give up or take up HH++
Proteins are extremely abundant in the cell
The more limited number of proteins in the plasma reinforce the bicarbonate system in the ECFECF
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PROTEIN BUFFER SYSTEMPROTEIN BUFFER SYSTEMHemoglobin buffers HH++ from metabolically
produced COCO22 in the plasma only
As hemoglobin releases OO22 it gains a great affinity for HH++
HHbb
O2
O2 O2
O2
H+
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PROTEIN BUFFER SYSTEMPROTEIN BUFFER SYSTEMHH++ generated at the tissue level from
the dissociation of HH22COCO33 produced by the addition of COCO22
Bound HH++ to Hb Hb (Hemoglobin) does not contribute to the acidity of blood
HHbb
O2
O2 O2
O2
H+
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PROTEIN BUFFER SYSTEMPROTEIN BUFFER SYSTEMAs HHbHHb picks up OO22 from the lungs the HbHb
which has a higher affinity for OO22 releases HH++ and picks up OO22
Liberated HH++ from HH22OO combines with HCOHCO33--
HCOHCO33-- HH22COCO33 COCO22 (exhaled)
HHbb
O2
O2 O2
H+
O2
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PROTEIN BUFFER SYSTEMPROTEIN BUFFER SYSTEMVenous blood is only slightly more acidic
than arterial blood because of the tremendous buffering capacity of HbHb
Even in spite of the large volume of HH++ generating COCO22 carried in venous blood
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Pr - added H+ + Pr -
PROTEIN BUFFER SYSTEMPROTEIN BUFFER SYSTEMProteins can act as a buffer for both
acids and basesProtein buffer system works
instantaneously making it the most powerful in the body
75% of the body’s buffer capacity is controlled by proteinBicarbonate and phosphate buffer
systems require several hours to be effective
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PROTEIN BUFFER SYSTEMPROTEIN BUFFER SYSTEMProteins are very large, complex
molecules in comparison to the size and complexities of acids or bases
Proteins are surrounded by a multitude of negative charges on the outside and numerous positive charges in the crevices of the molecule
-
-
-- - - -
----
--
------------
-
--
-
- - - -
+
+++
++
++++
+
++
++ +++
++
++
+++
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PROTEIN BUFFER SYSTEMPROTEIN BUFFER SYSTEMH+ ions are attracted to and held from
chemical interaction by the negative charges
-
-
-- - - -
----
--
------------
-
--
-
- - - -
+
+++
++
++++
+
++
++ +++
++
++
+++
H+
H+
H+
H+ H+ H+ H+ H+ H+ H+
H+
H+
H+
H+
H+H+H+H+H+H+H+
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PROTEIN BUFFER SYSTEMPROTEIN BUFFER SYSTEMOH- ions which are the basis of
alkalosis are attracted by the positive charges in the crevices of the protein
-
-
-- - - -
----
--
------------
-
--
-
- - - -
+
+++
++
++++
+
++
++ +++
++
++
+++
OH-
OH-
OH-
OH-
OH-OH-
OH-
OH-
OH-OH-
OH-
OH-
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PROTEIN BUFFER SYSTEMPROTEIN BUFFER SYSTEM
-
-
-- - - -
----
--
------------
-
--
-
- - - -
+
+++
++
++++
+
++
++ +++
++
++
+++
OH-
OH-
OH-
OH-
OH-OH-
OH-
OH-
OH-OH-
OH-
OH-H+
H+
H+
H+ H+ H+ H+ H+ H+ H+
H+
H+
H+
H+
H+H+H+H+H+H+H+
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BICARBONATE BUFFER BICARBONATE BUFFER SYSTEMSYSTEM
3) Bicarbonate Buffer System3) Bicarbonate Buffer SystemPredominates in extracellular fluid (ECFECF)
HH22COCO33 added H added H++ + HCO + HCO33--
HCOHCO33--
HH22COCO33
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BICARBONATE BUFFER BICARBONATE BUFFER SYSTEMSYSTEMThis system is most important because
the concentration of both components can be regulated:Carbonic acidCarbonic acid by the respiratory
systemBicarbonateBicarbonate by the renal system
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BICARBONATE BUFFER BICARBONATE BUFFER SYSTEMSYSTEM
HH22COCO33 HH++ + HCO + HCO33--
Hydrogen ions generated by metabolism or by ingestion react with bicarbonate base to form more carbonic acid
HCOHCO33--
HH22COCO33
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BICARBONATE BUFFER BICARBONATE BUFFER SYSTEMSYSTEMEquilibrium shifts toward the formation of
acidHydrogen ions that are lost (vomiting)
causes carbonic acid to dissociate yielding replacement HH++ and bicarbonate
HH++ HCOHCO33--
HH22COCO33
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Loss of HCl
Addition of lactic acid
BICARBONATE BUFFER BICARBONATE BUFFER SYSTEMSYSTEM
HH++ HCOHCO33--
HH22COCO33HH22
OOCOCO22+ ++
Exercise
Vomiting
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1) Buffer Systems1) Buffer Systems
2) Respiratory 2) Respiratory ResponsesResponses
3) Renal Responses3) Renal Responses4) Intracellular Shifts of Ions4) Intracellular Shifts of Ions
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RESPIRATORY RESPONSERESPIRATORY RESPONSENeurons in the medulla oblongata and
pons constitute the Respiratory CenterRespiratory CenterStimulation and limitation of respiratory
rates are controlled by the respiratory center
Control isaccomplished byresponding to CO2
and H+
concentrations inthe blood
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RESPIRATORY RESPIRATORY CENTERCENTER
Respiratory centers
Medulla oblongata
Pons
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CHEMOSENSITIVE AREASCHEMOSENSITIVE AREASChemosensitive areas of the
respiratory center are able to detect blood concentration levels of CO2 and H+
Increases in CO2 and H+ stimulate the respiratory centerThe effect is to raise
respiration rates But the effectdiminishes in1 - 2 minutes
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CHEMOSENSITIVE AREASCHEMOSENSITIVE AREASThe effect of
stimulating the respiratory centers by increased CO2
and H+ is weakened in environmentally increased CO2 levels
Symptoms may persist for several days
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CHEMORECEPTORSCHEMORECEPTORSChemoreceptors are also present in
the carotidcarotid and aorticaortic arteries which respond to changes in partial pressures of O2 and CO2 or pH
Increased levels ofCO2 (low pHpH) ordecreased levels ofO2 stimulaterespiration ratesto increase
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CHEMORECEPTORSCHEMORECEPTORSOverall compensatory response is:
HyperventilationHyperventilation in response to increased CO2 or H+ (low pHpH)
HypoventilationHypoventilation in response to decreased CO2 or H+ (high pHpH)
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RESPIRATORY CONTROL OF pHRESPIRATORY CONTROL OF pH
pH rises toward normal
rate and depth of breathing increase
CO2 eliminated in lungs
H+ stimulates respiratory center in medulla oblongata
H2CO3 H+ + HCO3-
H+ acidosis; pH drops
CO2 + H2O H2CO3
cell production of CO2 increases
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1) 1) Buffer SystemsBuffer Systems2) Respiratory Responses2) Respiratory Responses
3) Renal Responses3) Renal Responses4) Intracellular Shifts of Ions4) Intracellular Shifts of Ions
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RENAL RESPONSERENAL RESPONSEThe kidney compensates for Acid - Acid -
BaseBase imbalance within 24 hours and is responsible for long term control
The kidney in response:To AcidosisTo Acidosis
Retains bicarbonate ions and eliminates hydrogen ions
To AlkalosisTo AlkalosisEliminates bicarbonate ions and retains hydrogen ions
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ACIDIFICATION ACIDIFICATION OF URINE BY OF URINE BY
EXCRETION OF EXCRETION OF AMMONIAAMMONIA
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ACIDIFICATION OF URINE BY EXCRETION OF ACIDIFICATION OF URINE BY EXCRETION OF AMMONIAAMMONIA
Capillary Distal Tubule Cells
Tubular urine to be excreted
NH2
H+
NH3
NH2
H+
NH3
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Capillary Distal Tubule Cells
Tubular Urine
NH3
Na+
Cl-+H2CO
3
HCO3-+
NaCl
NaHCO3
Click Mouse to Start
Animation
NaHCO3
NH3Cl-
H+
NH4ClClick Mouse to See Animation
Again
Notice theH+ - Na+
exchange to maintain
electrical neutrality
ACIDIFICATION OF URINE BY EXCRETION OF ACIDIFICATION OF URINE BY EXCRETION OF AMMONIAAMMONIA
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Capillary Distal Tubule Cells
Tubular Urine
NH3
Na+
Cl-+H2CO
3
HCO3-+
NaCl
NaHCO3
Click Mouse to Start
Animation
NaHCO3
NH3Cl-
H+
NH4ClClick Mouse to See Animation
Again
Notice theH+ - Na+
exchange to maintain
electrical neutrality
ACIDIFICATION OF URINE BY EXCRETION OF ACIDIFICATION OF URINE BY EXCRETION OF AMMONIAAMMONIA
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RESPIRATORY / EXCRETORY RESPIRATORY / EXCRETORY RESPONSERESPONSE
COCO22 + H + H22O HO H22COCO33 H H++ + HCO + HCO33--
Hyperventilation removes HH++ ion concentrations
Hypoventilation increases HH++ ion concentrations
Kidneys eliminate or retainHH++ or bicarbonate ions
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1) 1) Buffer SystemsBuffer Systems2) Respiratory Responses2) Respiratory Responses
3) Renal Responses3) Renal Responses
4) Intracellular Shifts of 4) Intracellular Shifts of IonsIons
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HYPERKALEMIAHYPERKALEMIAHyperkalemiaHyperkalemia is generally associated
with acidosisAccompanied by a shift of H+ ions
into cells and K+ ions out of the cell to maintain electrical neutrality
H+
K+
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HYPERKALEMIAHYPERKALEMIAHyperkalemia is an elevated serum K+
H+ ions are buffered in cell by proteins
Acidosis may cause Hyperkalemia and Hyperkalemia may cause Acidosis
H+
K+
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HYPOKALEMIAHYPOKALEMIAHypokalemiaHypokalemia is generally associated
with reciprocal exchanges of H+ and K+ in the opposite directionAssociated with alkalosis
Hypokalemia is a depressed serum K+
H+
K+
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ELECTROLYTE SHIFTSELECTROLYTE SHIFTS
cell
HH++
KK++
AcidosisAcidosisCompensatory Response Result
- HH++ buffered intracellularly
- Hyperkalemia
HH++
KK++
cell
AlkalosisAlkalosisCompensatory Response Result
- Tendency to correct alkalosis
- Hypokalemia
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ACID - BASE BALANCEACID - BASE BALANCE