acid base balance

ADVANCED ADVANCED PHYSIOLOGYPHYSIOLOGY

ACID BASE ACID BASE BALANCEBALANCE

InstructorTerry Wiseth

NORTHLANDNORTHLAND

COLLEGECOLLEGE

InstructorTerry Wiseth

NORTHLANDNORTHLAND

COLLEGECOLLEGE

2

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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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

AcidsAcids

Acids = Acids = BasesBasesAcids > Acids > BasesBases

Acids < Acids < BasesBases

AcidsAcids

Buffers

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The need for the existence of multiple mechanisms involved in Acid-BaseAcid-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

6


The task imposed on the mechanisms that maintain Acid-BaseAcid-Base homeostasis is largeMetabolic pathways

are continuously consuming or producing HH++

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 - BaseAcid - Base balance is primarily 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

HH++ ion has special significance because of the narrow ranges that it must be maintained in order to be compatible with living systems

12


Norm

al

Primarily controlled by regulation of HH++ 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 threethree 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 leveldecreases and the bloodbecomes more BaseBase

When breathing is decreased,the blood carbon dioxide levelincreases and the blood becomes more AcidicAcidic

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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Click Here

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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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Click Here

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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-BaseAcid-Base balanceAcidosisAcidosisAlkalosisAlkalosis

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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


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-BaseAcid-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 a normal 20:1 base toacid 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

--

This process 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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COCO22

Red Blood CellRed Blood CellSystemic CirculationSystemic Circulation

HH22OO

HH++ HCOHCO33--


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 IntermediateIntermediateby-productsby-productsLactic acidPyruvic acidAcetoacetic acidFatty 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 VegetablesVegetablesBreakdown producesbases which can helpto equalize acidproduction

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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

72

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

HbCl-

H+

H+

H+

H+

H+

H+

H+

H+

Cl-

Cl-

Cl-

Cl-

Cl-

Cl-

Red Blood Cell

Cl-

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COCO22

COCO22

Red Blood CellRed Blood Cell Systemic CirculationSystemic Circulation


HCOHCO33--

ClCl--

(Chloride (Chloride Shift)Shift)

COCO22 diffuses into the plasma and into diffuses into the plasma and into

the RBCthe RBC

Within the RBC, the hydration of COWithin the RBC, the hydration of CO22 is is

catalyzed by carbonic anhydrasecatalyzed by carbonic anhydrase

Bicarbonate thus formed diffuses into Bicarbonate thus formed diffuses into plasmaplasma


TissuesTissues

PlasmaPlasma

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BICARBONATE DIFFUSIONBICARBONATE DIFFUSION

Red Blood CellRed Blood Cell Pulmonary CirculationPulmonary Circulation


HCOHCO33--

ClCl--

AlveolusAlveolus

PlasmaPlasma

COCO22Bicarbonate diffuses back into RBC in Bicarbonate diffuses back into RBC in pulmonary capillaries and reacts with pulmonary capillaries and reacts with hydrogen ions to form carbonic acidhydrogen ions to form carbonic acid

The acid breaks down to COThe acid breaks down to CO2 2 and waterand water

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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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PANCREATIC CELL PANCREATIC CELL SECRETIONSECRETION

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 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

82

ACIDOSIS / ALKALOSISACIDOSIS / ALKALOSISDeviations from normal Acid-Base

status are divided into fourfour 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 AcidosisMetabolic Acidosis and and Metabolic Metabolic

AlkalosisAlkalosiscaused by an imbalance in the production and excretion of acids or bases by the kidneys

Respiratory Acidosis and Respiratory Alkalosiscaused 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


e


e Bicarbonate

7.4

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ACIDOSISACIDOSISAcidosis is a decreasedecrease in pH below 7.35

Which means a relative increase of HH++ 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 Acidosis1) Respiratory Acidosis2) Metabolic Acidosis2) Metabolic Acidosis

H+

H+

H+

H+

H+H+

H+

H+

H+

H+

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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H+

H+

H+

H+

H+H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

1) Respiratory alkalosis1) Respiratory alkalosis2) Metabolic alkalosis2) Metabolic alkalosis

ALKALOSISALKALOSIS

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RESPIRATORY RESPIRATORY ACIDOSISACIDOSIS

90

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

91

HYPOVENTILATIONHYPOVENTILATION

Hypo = “Under”

Elimination of CO2

H+

pH

92

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 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

96

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

101

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

102

RESPIRATORY ACIDOSISRESPIRATORY ACIDOSIS4) Collapse of lung4) Collapse of lung

Compression injury, open thoracic Compression injury, open thoracic woundwound

Left lung collapsed

103

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

104


- 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-

105


-breathing is suppressed holding CO2 in body-pH = 7.1

H2CO

3

HCO3-

2 20:

CO2

CO2

CO2

CO2

106


BODY’S COMPENSATION-kidneys conserve HCO3

- ions to restore the normal 40:2 ratio (20:1)-kidneys eliminate H+ ion in acidic urine

H2CO

3

HCO3-

2 30:

HCO3-

H2CO

3

HCO3-

H+

+

acidic urine

107


- 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-

108

RESPIRATORY RESPIRATORY ALKALOSISALKALOSIS

109

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

110


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

111

HYPERVENTILATIONHYPERVENTILATION

Hyper = “Over”

Elimination of CO2

H+

pH

112

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)

113

RESPIRATORY ALKALOSISRESPIRATORY ALKALOSISAnxiety is an emotional

disturbanceThe most common cause

of hyperventilation, and thus respiratory alkalosis, is anxiety

114

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

115

RESPIRATORY ALKALOSISRESPIRATORY ALKALOSISRespiratory center Respiratory center

lesionslesionsDamage to brain Damage to brain

centers responsible centers responsible for monitoring for monitoring breathing ratesbreathing ratesTumorsTumorsStrokesStrokes

116

RESPIRATORY ALKALOSISRESPIRATORY ALKALOSISFFeverever

Rapid shallow Rapid shallow breathing blows off breathing blows off too much too much COCO22

117

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

118

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

119

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

120

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+

121

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

122

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


- HCO3- ions replaced by Cl- ions

123


-metabolic balance before onset of alkalosis-pH = 7.4

H2CO

3

HCO3-

1 20:



(Na+) HCO3-

(K+) HCO3-

(Mg++) HCO3-

(Ca++) HCO3-

124


-respiratory alkalosis-pH = 7.7-hyperactive breathing “ blows off ” CO2

H2CO

3 HCO3

-

0.5 20:

CO2

CO2 + H2O

125


BODY’S COMPENSATION- kidneys conserve H+ ions and eliminate HCO3

- in alkaline urine

H2CO

3

HCO3

-

0.5 15:

HCO3-

Alkaline Urine

126



- HCO3- ions replaced by Cl- ions

H2CO

3

HCO3-

0.5 10:

Cl-

Chloride containing solution

127

RESPIRATORYRESPIRATORYACIDOSIS / ALKALOSISACIDOSIS / ALKALOSIS

COCO22 + H + H22OO HH22COCO33 HH++ + + HCOHCO33

--

Respiratory Acidosis

Respiratory Alkalosis

128

METABOLIC ACIDOSISMETABOLIC ACIDOSIS

129

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

130

METABOLIC ACIDOSISMETABOLIC ACIDOSISAny acid-base

imbalance not attributable to COCO22 is classified as metabolicMetabolic

production of AcidsAcids

Or loss of BasesBases

131

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 amountof carbon dioxide

132

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

133

METABOLIC ACIDOSISMETABOLIC ACIDOSISMetabolic acidosis is always

characterized by a reduction in plasma HCOHCO33

-- while COCO22 remains normal

HCO3-

CO2

Plasma Levels

134

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

135

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

136

METABOLIC ACIDOSISMETABOLIC ACIDOSIS1) Ingesting An Acid1) Ingesting An Acid

Most substances that cause acidosis when ingested are considered poisonous

Examples includewood alcohol(methanol) andantifreeze(ethylene glycol)

However, even an overdoseof aspirin (acetylsalicylic acid)can cause metabolic acidosis

137

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

138

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++

139

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+

140

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

141


3) Kidney 3) Kidney InsufficienciesInsufficienciesEven the production

of normal amounts of acid may lead to acidosis when the kidneys aren't functioning normally

142

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

143

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

144


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

145

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

146

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

147

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

148


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

149


When acidosis is severe, bicarbonate may be given intravenouslyBicarbonate provides

only temporary relief and may cause harm

150


- 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


- lactate solution used in therapy isconverted to bicarbonate ionsin the liver

0.5 10

151


-metabolic balance before onset of acidosis-pH 7.4



(Na+) HCO3-

(K+) HCO3-

(Mg++) HCO3-

(Ca++) HCO3-

H2CO

3

HCO3-

1 20:

152


-HCO3- decreases because of excess

presence of ketones, chloride or organic ions-pH 7.1

H2CO

3

HCO3-

1 10:= 7.4

153


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

154


- 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

155

METABOLIC ALKALOSISMETABOLIC ALKALOSIS

156

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

157

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--

158

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 by IV

159

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 )

160

METABOLIC ALKALOSISMETABOLIC ALKALOSIS1) Ingestion of Alkaline Substances1) Ingestion of Alkaline Substances

Influx of NaHCONaHCO33

161

METABOLIC ALKALOSISMETABOLIC ALKALOSISBaking soda (NaHCONaHCO33) often used as a

remedy for gastric hyperacidity

NaHCONaHCO33 dissociates to NaNa++ and HCOHCO33--

162

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++

163

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

http://www.prevacid-prilosec-acid-reflux-gerd.com/pricing.html

164

METABOLIC ALKALOSISMETABOLIC ALKALOSIS2) Vomiting (abnormal loss of HCl)2) Vomiting (abnormal loss of HCl)Excessive loss of H+

165

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

166

HCl


K+

H+ Cl-

HCO3-


The bicarbonate is neutralized as HClHCl is reabsorbed by the plasma from the digestive tract

H2CO

3

167


HCl K+

HCO3-


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

168

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+

169


- 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


- HCO3- ions replaced by Cl- ions1.2

525

170


- metabolic balance before onset of alkalosis- pH = 7.4



(Na+) HCO3-

(K+) HCO3-

(Mg++) HCO3-

(Ca++) HCO3-

H2CO

3

HCO3-

1 20:

171


- pH = 7.7- HCO3

- increases because of loss of chloride ions or excess ingestion of NaHCO3

HCO3

-

1 40:

H2CO

3

172

H2CO

3

HCO3-


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

:

173


- Therapy required to restore metabolic balance- HCO3

- ions replaced by Cl- ions

H2CO

3

HCO3-

1.25 25:

Cl-

Chloride containing solution

174

ACIDOSISACIDOSISdecreasedremoval 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+

concentration

depression ofnervous system

accumulationof CO2 in blood

accumulationof acid in blood

excessive lossof NaHCO3 from blood

respiratoryacidosis

175

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 plasma

H+

concentration

overexcitabilityof nervous

system

hyperventilation

loss of CO2 and

H2CO2 from blood

loss of acid accumulationof base

176

ACID – BASE DISORDERSACID – BASE DISORDERS

Clinical StateAcid-Base Disorder

Pulmonary Embolus Respiratory Alkalosis

Cirrhosis Respiratory Alkalosis

Pregnancy Respiratory Alkalosis

Diuretic Use Metabolic Alkalosis

Vomiting Metabolic Alkalosis

Chronic Obstructive Pulmonary Disease Respiratory Acidosis

Shock Metabolic Acidosis

Severe Diarrhea Metabolic Acidosis

Renal Failure Metabolic Acidosis

Sepsis (Bloodstream Infection)Respiratory Alkalosis,Metabolic Acidosis

177

RESPONSES TO:RESPONSES TO:ACIDOSIS AND ALKALOSISACIDOSIS AND 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

178

1)1) Buffer SystemsBuffer Systems2) Respiratory Responses2) Respiratory Responses

3) Renal Responses3) Renal Responses4) Intracellular Shifts of Ions4) Intracellular Shifts of Ions

179

BUFFERSBUFFERSBuffering systems provide an immediate

response to fluctuations in pHpH1) Phosphate1) Phosphate2) Protein2) Protein3) Bicarbonate Buffer System3) Bicarbonate Buffer System

180

BUFFERSBUFFERSA buffer is a combination of chemicals

in solution that resists any significant change in pHpH

Able to bind or release free HH++ ions

181

BUFFERSBUFFERSChemical buffers are able to react

immediately (within milliseconds)Chemical buffers are the first line of

defense for the body for fluctuations in pHpH

182

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++

183

Na2HPO4 + H+ NaH2PO4 + Na+

Alternately switches NaNa++ with HH++


H+ Na2HPO

4

+

NaH2PO

4

Click to animate

Na++

Disodium hydrogen phosphate

184

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


Na2HPO

4 Na2HPO

4Na2HPO

4

185

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


HPO4-

2

186

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

187

PROTEIN BUFFER SYSTEMPROTEIN BUFFER SYSTEM

Most important intracellular buffer (ICFICF)

The most plentiful buffer of the body

188

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

189

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+

190

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+

191

PROTEIN BUFFER SYSTEMPROTEIN BUFFER SYSTEMAs HH++HbHb 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

192

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

193

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

194

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

-

-

-- - - -

----

--

------------

-

--

-

- - - -

+

+++

++

++++

+

++

++ +++

++

++

+++

195

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+

196

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-

197

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+

198

BICARBONATE BUFFER BICARBONATE BUFFER SYSTEMSYSTEM

3) Bicarbonate Buffer System3) Bicarbonate Buffer SystemPredominates in extracellular fluid (ECFECF)

HCOHCO33- - + added H+ added H++ H H22COCO33

HCOHCO33--

HH22COCO33

199

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

200


HH22COCO33 HH++ + HCO + HCO33--

Hydrogen ions generated by metabolism or by ingestion react with bicarbonate base to form more carbonic acid

HCOHCO33--

HH22COCO33

201

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

202

Loss of HCl

Addition of lactic acid


HH++ HCOHCO33--

HH22COCO33HH22

OOCOCO22+ ++

Exercise

Vomiting

203

1) Buffer Systems1) Buffer Systems

2) Respiratory 2) Respiratory ResponsesResponses


204

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

205

RESPIRATORY RESPIRATORY CENTERCENTER

Respiratory centers

Medulla oblongata

Pons

206

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

CO2CO2

CO2CO2

CO2

CO2

CO2CO2

CO2Click to increase CO2

207

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

208

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

209

CHEMORECEPTORSCHEMORECEPTORSOverall compensatory response is:

HyperventilationHyperventilation in response to increased CO2 or H+ (low pHpH)

HypoventilationHypoventilation in response to decreased CO2 or H+ (high pHpH)

210

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

211

1) 1) Buffer SystemsBuffer Systems2) Respiratory Responses2) Respiratory Responses


212

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

213

ACIDIFICATION ACIDIFICATION OF URINE BY OF URINE BY

EXCRETION OF EXCRETION OF AMMONIAAMMONIA

214

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

WHAT HAPPENS

NEXT?

215


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


Dissociation of carbonic acid

216


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


217

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

218

1) 1) Buffer SystemsBuffer Systems2) Respiratory Responses2) Respiratory Responses

3) Renal Responses3) Renal Responses

4) Intracellular Shifts of 4) Intracellular Shifts of IonsIons

219

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+

220

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+

221

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+

222

ELECTROLYTE SHIFTSELECTROLYTE SHIFTS

cell

HH++

KK++

AcidosisAcidosisCompensatory Response Result

- HH++ buffered intracellularly

- Hyperkalemia

HH++

KK++

cell

AlkalosisAlkalosisCompensatory Response Result

- Tendency to correct alkalosis

- Hypokalemia

223

ENDEND

ACID - BASE BALANCEACID - BASE BALANCE

acid base balance

Documents

acidbase regulation

base load

renal regulation

regulation of h ions

ph buffers

blood ph minute

fixed acids

chemical processes