lecture on acid-base balance.ppt

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ACID BASE ACID BASE BALANCE BALANCE BY BY DR.ABUBAKKAR DR.ABUBAKKAR SIDDIQUE SIDDIQUE

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ACID BASE ACID BASE BALANCEBALANCE

BYBYDR.ABUBAKKAR DR.ABUBAKKAR

SIDDIQUESIDDIQUE

2

ACID BASE HOMEOSTASISACID BASE HOMEOSTASISEvery day, metabolic reactions in the body produce and

consume many moles of hydrogen ions (H+s). Yet, the [H+] level of most body fluids is low (in the nanomolar range) and is kept within narrow limits.

For example, the [H+] level of arterial blood is normally 35 to 45 nmol/L (pH 7.45 to 7.35).

Normally, the body maintains acid–base balance; inputs and outputs of acids and bases are matched so that the [H+] level stays relatively constant both outside and inside cells.

Abnormalities in pH have profound effects on all systems in the body and can have fatal consequences

3

ACID BASE HOMEOSTASISACID BASE HOMEOSTASISAcid-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

4

ACID BASE HOMEOSTASISACID BASE HOMEOSTASISThe 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

5

ACID BASE HOMEOSTASISACID BASE HOMEOSTASISThe 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

ACID BASE HOMEOSTASISACID BASE HOMEOSTASISThe 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

7

EFFECTS OF pHEFFECTS OF pHThe most general effect of pH changes

are on enzyme functionAlso affect excitability of nerve and

muscle cells

pHpH

ExcitabilityExcitability

8

ACID-BASE BALANCEACID-BASE BALANCE

9

ACID-BASE BALANCEACID-BASE BALANCE

Acid - BaseAcid - Base balance is primarily concerned with two ions:HydrogenHydrogen (H+) BicarbonateBicarbonate (HCO3

- )

H+ HCO3-

10

ACID-BASE BALANCEACID-BASE BALANCEDerangements

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

11

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

ACID-BASE BALANCEACID-BASE BALANCE

Normal

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

extracellular fluids

13

ACIDSACIDS

14

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

dissociate in solution to release HH++

Click Here

15

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

dissociate in solution to release HH++

Click Here

16

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-

17

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-

18

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

19

BASESBASES

20

BASESBASESBases can be defined as:

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

hydrogen ion (OHOH--)

Click Here

21

BASESBASESBases can be defined as:

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

hydrogen ion (OHOH--)

Click Here

22

BASESBASESBases can be defined as:

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

hydrogen ion (OHOH--)

H+OH-

H+

OH-

H+

OH-

H+

OH-

23

BASESBASESPhysiologically important bases include:

Bicarbonate (HCOBicarbonate (HCO33- - ))

Biphosphate (HPOBiphosphate (HPO44-2 -2 ))

Biphosphate

24

The Acid Dissociation Constant The Acid Dissociation Constant Ka Shows the Strength of an Ka Shows the Strength of an

AcidAcidAt equilibrium, the rate of dissociation of an

acid to form H+ + A- and the rate of association of H+ and base A- to form HA are equal. The equilibrium constant (Ka), which is also called the ionization constant or acid dissociation constant, is given by the expression

25

26

27

28

pH SCALEpH SCALE

29

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

30

H+ ion is an acid

pH SCALEpH SCALE

31

OH- ion is a base

pH SCALEpH SCALE

32

H+ ion is an acidOH- ion is a base

pH SCALEpH SCALE

33

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

34

pH SCALEpH SCALEpH 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)

35

36

pH SCALEpH SCALELow 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)

37

pH SCALEpH SCALEpH = 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

38

39

pH SCALEpH SCALE

40

pH SCALEpH SCALE

41

ACID-BASE ACID-BASE REGULATIONREGULATION

42

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)

43

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

44

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

45

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

46

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

47

ACID-BASE REGULATIONACID-BASE REGULATIONEnzymes, hormones and ion

distribution are all affected by Hydrogen ion concentrations

48

ACIDOSIS / ACIDOSIS / ALKALOSISALKALOSIS

49

ACIDOSIS / ALKALOSISACIDOSIS / ALKALOSISAn abnormality in one or more of the pH

control mechanisms can cause one of two major disturbances in Acid-BaseAcid-Base balanceAcidosisAcidosisAlkalosisAlkalosis

50

ACIDOSIS / ALKALOSISACIDOSIS / ALKALOSISAcidosisAcidosis

A 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

51

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

52

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

53

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

54

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

55

INFLUENCES ON KINFLUENCES ON K++ LEVELS LEVELSWhen 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+

56

INFLUENCES ON KINFLUENCES ON K++ LEVELS LEVELSIf HH++ concentrations are high (acidosis)

than HH++ is secreted in greater amountsThis 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+

57

A relative increase in hydrogen ions results in acidosis acidosis

ACIDOSISACIDOSIS

H+ OH-

58

A relative increase in bicarbonate results in alkalosisalkalosis

ALKALOSISALKALOSIS

H+ OH-

59

AlkalosisAlkalosis

ACIDOSIS / ALKALOSISACIDOSIS / ALKALOSIS

H+ OH-

AcidosisAcidosis

H+ OH-

60

Normal ratio of HCOHCO33-- to HH22COCO33 is 20:1

HH22COCO33 is source of HH++ ions in the bodyDeviations from this ratio are used to

identify Acid-BaseAcid-Base imbalances

ACIDOSIS / ALKALOSISACIDOSIS / ALKALOSISBASE ACID

H2CO3

H+

HCO3-

61

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

62

ACIDOSIS / ALKALOSISACIDOSIS / ALKALOSISNormal values of bicarbonate

(arterial)pH pH = 7.4PCOPCO22 = 40 mm HgHCOHCO33

-- = 24 meq/L

63

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

64

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

65

SOURCES OF SOURCES OF HYDROGEN IONS HYDROGEN IONS

C C C C C CH H H H H H

HHHHHH

66

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-products4) Metabolic Intermediate by-products5) Some Disease processes5) Some Disease processes

67

SOURCES OF HYDROGEN SOURCES OF HYDROGEN IONSIONS1) Cellular Metabolism1) Cellular Metabolism of

carbohydrates release COCO22 as a waste productAerobic respirationCC66HH1212OO66 CO CO22 + H + H22O + EnergyO + Energy

68

SOURCES OF HYDROGEN SOURCES OF HYDROGEN IONSIONSCOCO22 diffuses into the bloodstream where

the reaction: COCO2 2 + H+ H22O O H 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

69

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

70

CARBON DIOXIDE DIFFUSIONCARBON DIOXIDE DIFFUSION

COCO22

COCO22

Red Blood CellRed Blood Cell Systemic 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

71

CARBON DIOXIDE DIFFUSIONCARBON DIOXIDE DIFFUSION

COCO22

Red Blood CellRed Blood Cell Systemic CirculationSystemic Circulation

HH22OO

HH++ HCOHCO33--

carboniccarbonicanhydraseanhydrase

PlasmaPlasma

COCO22 COCO22 COCO22 COCO22 COCO22 COCO22COCO22

Click for Carbon Dioxide diffusion

++ ++

TissuesTissues

HH++

ClCl--

HbHbHH++ is buffered is buffered

by Hemoglobinby Hemoglobin

72

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

SauerkrautYogurtCitric acid in fruits

73

SOURCES OF HYDROGEN SOURCES OF HYDROGEN IONS IONS

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

74

SOURCES OF HYDROGEN SOURCES OF HYDROGEN IONS IONS

4) Metabolic 4) Metabolic IntermediateIntermediateby-productsby-productsLactic acidPyruvic acidAcetoacetic acidFatty acids

CC66HH1212OO66 2 2 CC33HH66OO33

75

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

76

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

77

SOURCES OF SOURCES OF BICARBONATE IONSBICARBONATE IONS

78

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

79

1) CO1) CO2 2 DIFFUSIONDIFFUSIONHemoglobin 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-

80

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 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

carboniccarbonicanhydraseanhydrase

TissuesTissues

PlasmaPlasma

81

BICARBONATE DIFFUSIONBICARBONATE DIFFUSIONRed Blood CellRed Blood Cell Pulmonary CirculationPulmonary Circulation

COCO22 HH22OO HH++ HCOHCO33--++ ++

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

82

BICARBONATE DIFFUSIONBICARBONATE DIFFUSIONRed Blood CellRed Blood Cell Pulmonary CirculationPulmonary Circulation

COCO22 HH22OO

HH++

++ ++ HCOHCO33--

ClCl--

AlveolusAlveolus

PlasmaPlasma

COCO22

COCO22 HH22OO

83

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

84

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-

85

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-

86

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

87

ACIDOSIS / ACIDOSIS / ALKALOSISALKALOSIS

88

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

89

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

90

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

91

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

=

92

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-

93

ACIDOSISACIDOSIS1) 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+

94

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

95

RESPIRATORY RESPIRATORY ACIDOSISACIDOSIS

96

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

97

HYPOVENTILATIONHYPOVENTILATIONHypo = “Under”

Elimination of CO2H+

pH

98

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

99

RESPIRATORY ACIDOSISRESPIRATORY ACIDOSISHyperkapnia is the underlying cause of

Respiratory AcidosisRespiratory AcidosisUsually the result of decreased COCO22

removal from the lungs

CO2 CO2

CO2

CO2

CO2

CO2CO2

CO2CO2

CO2

CO2 CO2

CO2

pH

pH

100

RESPIRATORY ACIDOSISRESPIRATORY ACIDOSISThe speed and depth of breathing control

the amount of COCO22 in the bloodNormally when COCO22 builds up, the pHpH of the

blood falls and the blood becomes acidicHigh levels of COCO22 in the blood stimulate the

parts of the brain that regulate breathing, which in turn stimulate faster and deeper breathing

101

RESPIRATORY ACIDOSISRESPIRATORY ACIDOSISRespiratory 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

102

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

103

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

104

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

105

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

Vomit, anaphylaxis, tracheal cancer

106

RESPIRATORY ACIDOSISRESPIRATORY ACIDOSIS2) Decreased Respiration2) Decreased Respiration

Shallow, slow breathing Depression of the respiratory centers in

the brain which control breathing ratesDrug overdose

107

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

108

RESPIRATORY ACIDOSISRESPIRATORY ACIDOSIS4) Collapse of lung4) Collapse of lung

Compression injury, open thoracic Compression injury, open thoracic woundwound

Left lung collapsed

109

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

110

RESPIRATORY ACIDOSISRESPIRATORY ACIDOSIS

- metabolic balance before onset of acidosis- pH = 7.4

H2CO3

HCO3-

1 20:

H2CO3 : Carbonic Acid

HCO3- : Bicarbonate Ion

(Na+) HCO3-

(K+) HCO3-

(Mg++) HCO3-

(Ca++) HCO3-

111

RESPIRATORY ACIDOSISRESPIRATORY ACIDOSIS

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

H2CO

3

HCO3-

2 20:

CO2

CO2

CO2

CO2

112

RESPIRATORY ACIDOSISRESPIRATORY ACIDOSIS

BODY’S COMPENSATION-kidneys conserve HCO3

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

H2CO3

HCO3-

2 30:

HCO3-

H2CO3

HCO3-

H+

+

acidic urine

113

RESPIRATORY ACIDOSISRESPIRATORY ACIDOSIS

- therapy required to restore metabolic balance

- lactate solution used in therapy is converted to bicarbonate ions in the liver

H2CO3

HCO3-

2 40:

Lactate

Lactate

LIVER

HCO3-

114

RESPIRATORY RESPIRATORY ALKALOSISALKALOSIS

115

RESPIRATORY ALKALOSISRESPIRATORY ALKALOSISNormal 20:1 ratio is increased

pH of blood is above 7.4

H2CO3

HCO3-

1 20:=7.4

H2CO3 HCO3 -

0.5

20:= 7.4

116

RESPIRATORY ALKALOSISRESPIRATORY ALKALOSISCause is Hyperventilation

Leads 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

CO2CO

2

CO2

CO2

CO2

CO2

117

HYPERVENTILATIONHYPERVENTILATIONHyper = “Over”

Elimination of CO2H+

pH

118

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)

119

RESPIRATORY ALKALOSISRESPIRATORY ALKALOSISAnxiety is an emotional

disturbanceThe most common cause

of hyperventilation, and thus respiratory alkalosis, is anxiety

120

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

121

RESPIRATORY ALKALOSISRESPIRATORY ALKALOSISRespiratory center Respiratory center

lesionslesionsDamage to brain Damage to brain

centers responsible centers responsible for monitoring for monitoring breathing ratesbreathing ratesTumorsTumorsStrokesStrokes

122

RESPIRATORY ALKALOSISRESPIRATORY ALKALOSISFFeverever

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

123

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

124

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

125

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

126

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+

127

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

128

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

129

RESPIRATORY ALKALOSISRESPIRATORY ALKALOSIS

-metabolic balance before onset of alkalosis-pH = 7.4

H2CO3

HCO3-

1 20:

H2CO3 : Carbonic Acid

HCO3- : Bicarbonate Ion

(Na+) HCO3-

(K+) HCO3-

(Mg++) HCO3-

(Ca++) HCO3-

130

RESPIRATORY ALKALOSISRESPIRATORY ALKALOSIS

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

H2CO

3 HCO3 -

0.5 20:

CO2

CO2 + H2O

131

RESPIRATORY ALKALOSISRESPIRATORY ALKALOSIS

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

- in alkaline urine

H2CO3

HCO3-

0.5 15:

HCO3-

Alkaline Urine

132

RESPIRATORY ALKALOSISRESPIRATORY ALKALOSIS

- therapy required to restore metabolic balance

- HCO3- ions replaced by Cl- ions

H2CO3

HCO3-

0.5 10:

Cl-

Chloride containing solution

133

RESPIRATORYRESPIRATORYACIDOSIS / ALKALOSISACIDOSIS / ALKALOSIS

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

-- Respiratory Acidosis

Respiratory Alkalosis

134

METABOLIC ACIDOSISMETABOLIC ACIDOSIS

135

METABOLIC ACIDOSISMETABOLIC ACIDOSISOccurs when there is a decrease in

the normal 20:1 ratioDecrease in blood pHpH and

bicarbonate levelExcessive HH++ or decreased HCOHCO33

--

H2CO3

HCO3-

1 20:= 7.4H2CO

3

HCO3-

1 10:= 7.4

136

METABOLIC ACIDOSISMETABOLIC ACIDOSISAny acid-base imbalance not

attributable to COCO22 is classified as metabolicMetabolic production of AcidsAcids Or loss of BasesBases

137

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

138

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

139

METABOLIC ACIDOSISMETABOLIC ACIDOSISMetabolic acidosis is always

characterized by a reduction in plasma HCOHCO33

-- while COCO22 remains normal

HCO3-

CO2

Plasma Levels

140

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

141

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

142

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

143

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

144

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++

145

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+

146

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

147

METABOLIC ACIDOSISMETABOLIC ACIDOSIS3) Kidney 3) Kidney

InsufficienciesInsufficienciesEven the production

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

148

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

149

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

150

METABOLIC ACIDOSISMETABOLIC ACIDOSIS4) Strenuous Exercise4) Strenuous Exercise

Muscles resort to anaerobic glycolysis during strenuous exercise

Anaerobic respiration leads to the production of large amounts of lactic acid

C6H12O6 2C3H6O3 + ATP (energy)

Enzymes

Lactic Acid

151

METABOLIC ACIDOSISMETABOLIC ACIDOSIS5) Severe Diarrhea5) Severe Diarrhea

Fluids rich in HCOHCO33-- are released and

reabsorbed during the digestive processDuring diarrhea this HCOHCO33

-- is lost from the body rather than reabsorbed

152

METABOLIC ACIDOSISMETABOLIC ACIDOSIS5) Severe Diarrhea5) Severe Diarrhea

The loss of HCOHCO33-- without a

corresponding loss of H+ lowers the pHLess HCOHCO33

-- is available for buffering HH++

Prolonged deep (from duodenum) vomiting can result in the same situation

153

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

154

METABOLIC ACIDOSISMETABOLIC ACIDOSISMetabolic acidosis may

also be treated directlyIf the acidosis is mild,

intravenous fluids and treatment for the underlying disorder may be all that's needed

155

METABOLIC ACIDOSISMETABOLIC ACIDOSISWhen acidosis is severe,

bicarbonate may be given intravenouslyBicarbonate provides

only temporary relief and may cause harm

156

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

157

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-

H2CO3

HCO3-

1 20:

158

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

159

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

160

METABOLIC ACIDOSISMETABOLIC ACIDOSIS

- therapy required to restore metabolic balance- lactate solution used in therapy is converted to bicarbonate ions in the liver

H2CO3

HCO3-

0.5 10:

Lactate

Lactate containing solution

161

METABOLIC ALKALOSISMETABOLIC ALKALOSIS

162

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

163

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--

164

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

165

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 )

166

METABOLIC ALKALOSISMETABOLIC ALKALOSIS1) Ingestion of Alkaline Substances1) Ingestion of Alkaline SubstancesInflux of NaHCONaHCO33

167

METABOLIC ALKALOSISMETABOLIC ALKALOSISBaking soda (NaHCONaHCO33) often used as a

remedy for gastric hyperacidityNaHCONaHCO33 dissociates to NaNa++ and HCOHCO33

--

168

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++

169

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

170

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

171

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

172

HCl

METABOLIC ALKALOSISMETABOLIC ALKALOSIS

K+H+ Cl-

HCO3- Click to

View Animation

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

H2CO3

173

METABOLIC ALKALOSISMETABOLIC ALKALOSIS

HCl K+

HCO3- Click to

View 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

174

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+

175

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

176

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-

H2CO3

HCO3-

1 20:

177

METABOLIC ALKALOSISMETABOLIC ALKALOSIS

- pH = 7.7- HCO3

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

HCO3 -

1 40:

H2CO

3

178

H2CO3

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

:

179

METABOLIC ALKALOSISMETABOLIC ALKALOSIS

- Therapy required to restore metabolic balance- HCO3

- ions replaced by Cl- ions

H2CO3

HCO3-

1.25 25:

Cl-

Chloride containing solution

180

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

181

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

182

ACID – BASE DISORDERSACID – BASE DISORDERSClinical State Acid-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

183

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

184

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

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

185

BUFFERSBUFFERSBuffering systems provide an immediate

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

186

BUFFERSBUFFERSA buffer is a combination of chemicals

in solution that resists any significant change in pHpH

Able to bind or release free HH++ ions

187

BUFFERSBUFFERSChemical buffers are able to react

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

for the body for fluctuations in pHpH

188

1) Phosphate buffer system1) Phosphate buffer systemNa2HPO4 + H+ NaH2PO4

+ Na+ Most important in the intracellular

system

PHOSPHATE BUFFER SYSTEMPHOSPHATE BUFFER SYSTEM

H+ Na2HPO4

+

NaH2PO4

Click to animate

Na++

189

Na2HPO4 + H+ NaH2PO4 + Na+

Alternately switches NaNa++ with HH++

PHOSPHATE BUFFER SYSTEMPHOSPHATE BUFFER SYSTEM

H+ Na2HPO4

+

NaH2PO4

Click to animate

Na++

Disodium hydrogen phosphate

190

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

Na2HPO4 Na2HPO

4Na2HPO4

191

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

192

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

193

PROTEIN BUFFER SYSTEMPROTEIN BUFFER SYSTEMMost important

intracellular buffer (ICFICF)

The most plentiful buffer of the body

194

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

195

PROTEIN BUFFER SYSTEMPROTEIN BUFFER SYSTEMHemoglobin buffers HH++ from metabolically

produced COCO22 in the plasma onlyAs hemoglobin releases OO22 it gains a great

affinity for HH++

HHbb

O2

O2 O2

O2

H+

196

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+

197

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

198

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

199

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

200

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

--

-- - - --

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

------

-

- - - -

+

+++++

++++

+++

++ +++++

+++++

201

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+

202

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-

203

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+

204

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

205

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

206

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

207

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

208

Loss of HCl

Addition of lactic acid

BICARBONATE BUFFER BICARBONATE BUFFER SYSTEMSYSTEM

HH++ HCOHCO33--

HH22COCO33HH22

OOCOCO22+ ++

Exercise

Vomiting

209

1) Buffer Systems1) Buffer Systems2) Respiratory 2) Respiratory

ResponsesResponses3) Renal Responses3) Renal Responses

4) Intracellular Shifts of Ions4) Intracellular Shifts of Ions

210

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 CO2and H+

concentrations inthe blood

211

RESPIRATORY RESPIRATORY CENTERCENTER

Respiratory centers

Medulla oblongata

Pons

212

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

CO2CO2CO2

CO2

CO2CO2

CO2Click to increase CO2

213

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

214

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

215

CHEMORECEPTORSCHEMORECEPTORSOverall compensatory response is:

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

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

216

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

217

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

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

218

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

219

ACIDIFICATION ACIDIFICATION OF URINE BY OF URINE BY

EXCRETION OF EXCRETION OF AMMONIAAMMONIA

220

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?

221

Capillary Distal Tubule Cells

Tubular Urine

NH3

Na+

Cl-+H2CO3

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

Dissociation of carbonic acid

222

Capillary Distal Tubule Cells

Tubular Urine

NH3

Na+

Cl-+H2CO3

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

223

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

224

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

3) Renal Responses3) Renal Responses4) Intracellular Shifts of 4) Intracellular Shifts of

IonsIons

225

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+

226

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+

227

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+

228

ELECTROLYTE SHIFTSELECTROLYTE SHIFTS

cell

HH++

KK++

AcidosisAcidosisCompensatory Response Result

- HH++ buffered intracellularly- Hyperkalemia

HH++

KK++

cell

AlkalosisAlkalosisCompensatory Response Result

- Tendency to correct alkalosis- Hypokalemia

229

ENDENDACID - BASE BALANCEACID - BASE BALANCE