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ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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ADVANCED ADVANCED PHYSIOLOGY PHYSIOLOGY ACID BASE ACID BASE BALANCE BALANCE Instructor Terry Wiseth
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Page 1: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

ADVANCED ADVANCED PHYSIOLOGYPHYSIOLOGY

ACID BASE ACID BASE BALANCEBALANCE

InstructorTerry WisethInstructorTerry Wiseth

Page 2: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 3: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 4: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 5: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 6: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

EFFECTS OF pHEFFECTS OF pHThe most general effect of pH changes

are on enzyme functionAlso affect excitability of nerve and

muscle cells

pHpH

ExcitabilityExcitability

Page 7: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

ACID-BASE BALANCEACID-BASE BALANCE

Page 8: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

ACID-BASE BALANCEACID-BASE BALANCE

Acid - Base balance is mainly concerned with two ions:HydrogenHydrogen (H+)

BicarbonateBicarbonate (HCO3- )

H+ HCO3-

Page 9: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

ACID-BASE BALANCEACID-BASE BALANCEDerangements

of hydrogen and bicarbonate concentrations in body fluids are common in disease processes

Page 10: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 11: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

ACID-BASE BALANCEACID-BASE BALANCE

Norm

al

Primarily controlled by regulation of H+ ions in the body fluidsEspecially

extracellular fluids

Page 12: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

ACID-BASE ACID-BASE REGULATIONREGULATION

Page 13: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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)

Page 14: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 15: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 16: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 17: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 18: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

ACID-BASE REGULATIONACID-BASE REGULATIONEnzymes, hormones and ion

distribution are all affected by hydrogen ion concentrations

Page 19: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

ACIDSACIDS

Page 20: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

ACIDSACIDSAcids can be defined as a proton (HH++) donor Hydrogen containing substances which

dissociate in solution to release HH++

Click Here

Page 21: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

ACIDSACIDSAcids can be defined as a proton (HH++) donor Hydrogen containing substances which

dissociate in solution to release HH++

Click Here

Page 22: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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-

Page 23: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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-

Page 24: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 25: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

BASESBASES

Page 26: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

BASESBASESBases can be defined as:

A proton (HH++) acceptorMolecules capable of accepting a

hydrogen ion (OHOH--)

Click Here

Page 27: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

BASESBASESBases can be defined as:

A proton (HH++) acceptorMolecules capable of accepting a

hydrogen ion (OHOH--)

Click Here

Page 28: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

BASESBASESBases can be defined as:

A proton (HH++) acceptorMolecules capable of accepting a

hydrogen ion (OHOH--)

H+OH-

H+

OH-

H+

OH-

H+

OH-

Page 29: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

BASESBASES

Physiologically important bases include:Bicarbonate (HCOBicarbonate (HCO33

- - ))Biphosphate (HPOBiphosphate (HPO44

-2 -2 ))

Biphosphate

Page 30: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

pH SCALEpH SCALE

Page 31: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 32: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

H+ ion is an acid

pH SCALEpH SCALE

Page 33: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

OH- ion is a base

pH SCALEpH SCALE

Page 34: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

H+ ion is an acid

OH- ion is a base

pH SCALEpH SCALE

Page 35: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 36: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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)

Page 37: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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)

Page 38: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 39: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

pH SCALEpH SCALE

Page 40: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

pH SCALEpH SCALE

Page 41: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

ACIDOSIS / ACIDOSIS / ALKALOSISALKALOSIS

Page 42: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 43: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 44: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 45: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 46: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 47: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 48: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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+

Page 49: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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+

Page 50: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

A relative increase in hydrogen ions results in acidosis acidosis

ACIDOSISACIDOSIS

H+ OH-

Page 51: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

A relative increase in bicarbonate results in alkalosisalkalosis

ALKALOSISALKALOSIS

H+ OH-

Page 52: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

AlkalosisAlkalosis

ACIDOSIS / ALKALOSISACIDOSIS / ALKALOSIS

H+ OH-

AcidosisAcidosis

H+ OH-

Page 53: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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-

Page 54: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 55: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

ACIDOSIS / ALKALOSISACIDOSIS / ALKALOSISNormal values of bicarbonate

(arterial)pH pH = 7.4

PCOPCO22 = 40 mm Hg

HCOHCO33-- = 24 meq/L

Page 56: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 57: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 58: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

SOURCES OF SOURCES OF HYDROGEN IONS HYDROGEN IONS

C C C C C C

H H H H H H

HHHHHH

Page 59: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 60: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 61: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 62: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 63: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 64: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 65: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

SOURCES OF HYDROGEN SOURCES OF HYDROGEN IONS IONS 2) Food products2) Food products

SauerkrautYogurtCitric acid in fruits

Page 66: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

SOURCES OF HYDROGEN SOURCES OF HYDROGEN IONS IONS

3) Medications3) MedicationsMay stimulate HClHCl production by parietal cells of the stomach

Page 67: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 68: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 69: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 70: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

SOURCES OF SOURCES OF BICARBONATE IONSBICARBONATE IONS

Page 71: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 72: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 73: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 74: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 75: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

BICARBONATE DIFFUSIONBICARBONATE DIFFUSION

Red Blood CellRed Blood Cell Pulmonary CirculationPulmonary Circulation

COCO22 HH22OO

HH++

++ ++ HCOHCO33--

ClCl--

AlveolusAlveolus

PlasmaPlasma

COCO22

COCO22 HH22OO

Page 76: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 77: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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-

Page 78: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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-

Page 79: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 80: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

ACIDOSIS / ACIDOSIS / ALKALOSISALKALOSIS

Page 81: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 82: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 83: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 84: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

=

Page 85: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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-

Page 86: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

ACIDOSISACIDOSIS

1) Respiratory Acidosis2) Metabolic Acidosis

H+

H+

H+

H+

H+H+

H+

H+

H+

H+

H+

H+

H+

H+

H+H+

Page 87: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

H+

H+

H+

H+

H+H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

H+

1) Respiratory alkalosis2) Metabolic alkalosis

ALKALOSISALKALOSIS

Page 88: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

RESPIRATORY RESPIRATORY ACIDOSISACIDOSIS

Page 89: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 90: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

HYPOVENTILATIONHYPOVENTILATION

Hypo = “Under”

Elimination of CO2

H+

pH

Page 91: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 92: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 93: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 94: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 95: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 96: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 97: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 98: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

RESPIRATORY ACIDOSISRESPIRATORY ACIDOSIS1) Obstruction of air passages1) Obstruction of air passages

Vomit, anaphylaxis, tracheal cancer

Page 99: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

RESPIRATORY ACIDOSISRESPIRATORY ACIDOSIS2) Decreased Respiration2) Decreased Respiration

Shallow, slow breathing Depression of the respiratory centers in

the brain which control breathing ratesDrug overdose

Page 100: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 101: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

RESPIRATORY ACIDOSISRESPIRATORY ACIDOSIS4) Collapse of lung4) Collapse of lung

Compression injury, open thoracic Compression injury, open thoracic woundwound

Left lung collapsed

Page 102: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 103: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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-

Page 104: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

RESPIRATORY ACIDOSISRESPIRATORY ACIDOSIS

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

H2CO

3

HCO3-

2 20:

CO2 CO

2

CO2

CO2

Page 105: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 106: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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-

Page 107: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

RESPIRATORY RESPIRATORY ALKALOSISALKALOSIS

Page 108: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 109: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 110: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

HYPERVENTILATIONHYPERVENTILATION

Hyper = “Over”

Elimination of CO2

H+

pH

Page 111: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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)

Page 112: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

RESPIRATORY ALKALOSISRESPIRATORY ALKALOSISAnxiety is an emotional

disturbanceThe most common cause

of hyperventilation, and thus respiratory alkalosis, is anxiety

Page 113: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 114: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

RESPIRATORY ALKALOSISRESPIRATORY ALKALOSISRespiratory center Respiratory center

lesionslesionsDamage to brain Damage to brain

centers responsible centers responsible for monitoring for monitoring breathing ratesbreathing ratesTumorsTumorsStrokesStrokes

Page 115: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

RESPIRATORY ALKALOSISRESPIRATORY ALKALOSISFFeverever

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

Page 116: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 117: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 118: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 119: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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+

Page 120: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 121: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 122: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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-

Page 123: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

RESPIRATORY ALKALOSISRESPIRATORY ALKALOSIS

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

H2CO

3 HCO3

-

0.5 20:

CO2

CO2 + H2O

Page 124: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 125: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 126: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

RESPIRATORYRESPIRATORYACIDOSIS / ALKALOSISACIDOSIS / ALKALOSIS

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

--

Respiratory Acidosis

Respiratory Alkalosis

Page 127: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

METABOLIC ACIDOSISMETABOLIC ACIDOSIS

Page 128: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 129: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

METABOLIC ACIDOSISMETABOLIC ACIDOSISAny acid-base

imbalance not attributable to COCO22 is classified as metabolicMetabolic

production of AcidsAcids

Or loss of BasesBases

Page 130: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 131: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 132: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

METABOLIC ACIDOSISMETABOLIC ACIDOSISMetabolic acidosis is always

characterized by a reduction in plasma HCOHCO33

-- while COCO22 remains normal

HCO3-

CO2

Plasma Levels

Page 133: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 134: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 135: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 136: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 137: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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++

Page 138: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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+

Page 139: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 140: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 141: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 142: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 143: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 144: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 145: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 146: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 147: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 148: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

METABOLIC ACIDOSISMETABOLIC ACIDOSIS

When acidosis is severe, bicarbonate may be given intravenouslyBicarbonate provides

only temporary relief and may cause harm

Page 149: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 150: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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:

Page 151: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 152: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 153: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 154: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

METABOLIC ALKALOSISMETABOLIC ALKALOSIS

Page 155: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 156: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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--

Page 157: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 158: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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 )

Page 159: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Influx of NaHCONaHCO33

Page 160: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

METABOLIC ALKALOSISMETABOLIC ALKALOSISBaking soda (NaHCONaHCO33) often used as a

remedy for gastric hyperacidity

NaHCONaHCO33 dissociates to NaNa++ and HCOHCO33--

Page 161: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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++

Page 162: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 163: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 164: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 165: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 166: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 167: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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+

Page 168: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 169: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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:

Page 170: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

METABOLIC ALKALOSISMETABOLIC ALKALOSIS

- pH = 7.7- HCO3

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

HCO3

-

1 40:

H2CO

3

Page 171: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

:

Page 172: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 173: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 174: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 175: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 176: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 177: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

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

Page 178: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

BUFFERSBUFFERSBuffering systems provide an immediate

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

Page 179: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

BUFFERSBUFFERSA buffer is a combination of chemicals

in solution that resists any significant change in pHpH

Able to bind or release free HH++ ions

Page 180: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

BUFFERSBUFFERSChemical buffers are able to react

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

defense for the body for fluctuations in pHpH

Page 181: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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++

Page 182: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

Na2HPO4 + H+ NaH2PO4 + Na+

Alternately switches NaNa++ with HH++

PHOSPHATE BUFFER SYSTEMPHOSPHATE BUFFER SYSTEM

H+ Na2HPO

4

+

NaH2PO

4

Click to animate

Na++

Page 183: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 184: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 185: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 186: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

PROTEIN BUFFER SYSTEMPROTEIN BUFFER SYSTEM

Most important intracellular buffer (ICFICF)

The most plentiful buffer of the body

Page 187: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 188: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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+

Page 189: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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+

Page 190: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 191: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 192: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 193: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

-

-

-- - - -

----

--

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

-

--

-

- - - -

+

+++

++

++++

+

++

++ +++

++

++

+++

Page 194: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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+

Page 195: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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-

Page 196: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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+

Page 197: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 198: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 199: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 200: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 201: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

Loss of HCl

Addition of lactic acid

BICARBONATE BUFFER BICARBONATE BUFFER SYSTEMSYSTEM

HH++ HCOHCO33--

HH22COCO33HH22

OOCOCO22+ ++

Exercise

Vomiting

Page 202: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

1) Buffer Systems1) Buffer Systems

2) Respiratory 2) Respiratory ResponsesResponses

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

Page 203: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 204: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

RESPIRATORY RESPIRATORY CENTERCENTER

Respiratory centers

Medulla oblongata

Pons

Page 205: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 206: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 207: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 208: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

CHEMORECEPTORSCHEMORECEPTORSOverall compensatory response is:

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

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

Page 209: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 210: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

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

Page 211: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 212: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

ACIDIFICATION ACIDIFICATION OF URINE BY OF URINE BY

EXCRETION OF EXCRETION OF AMMONIAAMMONIA

Page 213: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 214: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 215: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 216: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

Page 217: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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

3) Renal Responses3) Renal Responses

4) Intracellular Shifts of 4) Intracellular Shifts of IonsIons

Page 218: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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+

Page 219: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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+

Page 220: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

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+

Page 221: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

ELECTROLYTE SHIFTSELECTROLYTE SHIFTS

cell

HH++

KK++

AcidosisAcidosisCompensatory Response Result

- HH++ buffered intracellularly

- Hyperkalemia

HH++

KK++

cell

AlkalosisAlkalosisCompensatory Response Result

- Tendency to correct alkalosis

- Hypokalemia

Page 222: ADVANCED PHYSIOLOGY ACID BASE BALANCE Instructor Terry Wiseth.

ENDEND

ACID - BASE BALANCEACID - BASE BALANCE


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