Acid base homeostasis

ACID BASEACID BASE
BALANCEBALANCE
Life is a struggle, not against sin, not against Money Power
. . but against hydrogen ions.

2
ACID BASE HOMEOSTASISACID BASE HOMEOSTASIS
♥Acid-Base homeostasis
involves chemicalchemical and
physiologicphysiologic processes
responsible for the
maintenance of the
acidity of body fluids at
levels that allow optimal
function of the whole
individual

3
♥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

4
♥The need for the existence of multiple
mechanisms involved in Acid-BaseAcid-Base
regulation stems from the critical
importance of the hydrogen ion (H+
)
concentration on the operation of many
cellular enzymes and function of vital
organs, most prominently the brain and
the heart

5
♥The task imposed on
the mechanisms that
maintain Acid-BaseAcid-Base
homeostasis is large
♠Metabolic 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

6
EFFECTS OF pHEFFECTS OF pH
♥The most general effect of pH changes
are on enzyme function
♠Also affect excitability of nerve and
muscle cells
p
H
p
Excitabilit
y
Excitabili

7
ACID-BASE BALANCEACID-BASE BALANCE

8
♥Acid - BaseAcid - Base balance is primarily
concerned with two ions:
♠HydrogenHydrogen (H+
)
♠BicarbonateBicarbonate (HCO3
-
)
H+ HCO3
-

9
♥Derangements of
hydrogen and
bicarbonate
concentrations in
body fluids are
common in
disease
processes

10
ACID-BASEACID-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

11
Norm
al
♥Primarily
controlled by
regulation of
HH++
ions in the
body fluids
♠Especially
extracellular
fluids

12
ACID-BASEACID-BASE
REGULATIONREGULATION

13
ACID-BASE REGULATIONACID-BASE REGULATION
♥Maintenance 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 Regulation
♦Reacts rapidly (seconds to minutes)
♠3)3) Renal RegulationRenal Regulation
♦Reacts slowly (minutes to hours)

14
♥Chemical 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
Buffe

15
♥Respiratory 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
CO
2
CO
2
CO
2
CO
2
CO
2CO
2
Cell
Metabolis
m

16
♥Respiratory RegulationRespiratory Regulation
♠When breathing is increased,
the blood carbon dioxide level
decreases and the blood
becomes more BaseBase
♠When breathing is decreased,
the blood carbon dioxide level
increases 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

17
♥Kidney 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

18
♥Enzymes, hormones and ion
distribution are all affected by
Hydrogen ion concentrations

20
ACIDSACIDS
♥Acids can be defined as a proton (HH++
)
donor
♥Hydrogen containing substances which
dissociate in solution to release HH++
Click Here

21
ACIDSACIDS
♥Acids can be defined as a proton (HH++
)
donor
♥Hydrogen containing substances which
dissociate in solution to release HH++
H+
OH-
H+
OH-
H+
O
H-
H+
OH-

22
ACIDSACIDS
♥Many 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+
O
H-
H+
OH-

23
ACIDSACIDS
♥Physiologically important acids include:
♠Carbonic acid (HCarbonic acid (H22 COCO33 ))
♠Phosphoric acid (HPhosphoric acid (H33 POPO44 ))
♠Pyruvic acid (CPyruvic acid (C33 HH44 OO33 ))
♠Lactic acid (CLactic acid (C33 HH66 OO33 ))
♥These acids are dissolved in body fluids
Lactic
acid
Pyruvic
acid
Phosphoric
acid

25
BASESBASES
♥Bases can be defined as:
♠A proton (HH++
) acceptor
♠Molecules capable of accepting a
hydrogen ion (OHOH--
)
Click Here

26
BASESBASES
♥Physiologically important bases include:
♠Bicarbonate (HCOBicarbonate (HCO33
--
))
♠Biphosphate (HPOBiphosphate (HPO44
-2-2
))
Biphosphat
e

27
♥pH refers to PPotential HHydrogen
♥Expresses hydrogen ion concentration in
water solutions
♥Water ionizes to a limited extent to form equal
amounts of HH++
ions and OHOH--
ions
♠HH22 OO HH++
+ OH+ OH--
♦HH++
ion is an acid
♦OHOH--
ion is a base
pH SCALEpH SCALE

28
♥H+
ion is an acid
pH SCALEpH SCALE

29
♥OH-
ion is a base
pH SCALEpH SCALE

30
♥Pure water is NeutralNeutral
♠ ( H+
= OH-
)
♦ pH = 7
♥AcidAcid
♠( H+
> OH-
)
♦pH < 7
♥BaseBase
♠( H+
< OH-
)
♦ pH > 7
♥Normal blood pH is 7.35 - 7.457.35 - 7.45
♥pH 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

31
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)

32
pH SCALEpH SCALE
♥Low pH values = high HH++
concentrations
♠HH++
concentration in denominator of
formula
♥Unit changes in pH represent a tenfold
change in HH++
concentrations
♠Nature of logarithms
pH = log 1 / HH++
concentration
4 X 10 -8
(0.00000004)

33
pH SCALEpH SCALE
♥pH = 4 is more acidic than pH = 6
♥pH = 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
Venou
s
Blood
Arteria
l Blood
7.3 7.57.46.8 8.0

36
ACIDOSIS /ACIDOSIS /
ALKALOSISALKALOSIS

37
ACIDOSIS / ALKALOSISACIDOSIS / ALKALOSIS
♥An abnormality in one or more of the pH
control mechanisms can cause one of
two major disturbances in Acid-BaseAcid-Base
balance
♠AcidosisAcidosis
♠AlkalosisAlkalosis

38
♥AcidosisAcidosis
♠A condition in which the blood has too
much acid (or too little base),
frequently resulting in a decrease in
blood pH
♥AlkalosisAlkalosis
♠A condition in which the blood has too
much base (or too little acid),
occasionally resulting in an increase in
blood pH

39
♥Acidosis and alkalosis are not diseases
but rather are the results of a wide
variety of disorders
♥The presence of
acidosis or
alkalosis provides
an important clue
to physicians that
a serious
metabolic
problem exists

40
♥pH changes have dramatic effects on
normal cell function
♠1)1) Changes in excitability of nerve
and muscle cells
♠2)2) Influences enzyme activity
♠3)3) Influences KK++
levels

41
CHANGES IN CELLCHANGES IN CELL
EXCITABILITYEXCITABILITY
♥pH decrease (more acidic) depresses
the central nervous system
♠Can lead to loss of consciousness
♥pH increase (more basic) can cause
over-excitability
♠Tingling sensations, nervousness,
muscle twitches

42
INFLUENCES ON ENZYMEINFLUENCES 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

43
INFLUENCES ON KINFLUENCES ON K++
LEVELSLEVELS
♥When reabsorbing NaNa++
from the filtrate
of the renal tubules KK++
or HH++
is secreted
(exchanged)
♥Normally KK++
is
secreted in much
greater amounts
than HH++
K+
K+
K+
K+
K+
K+
K+
Na+
Na+
Na+
Na+
Na+
Na+
H+

44
INFLUENCES ON KINFLUENCES ON K++
LEVELSLEVELS
♥If HH++
concentrations are high (acidosis)
than HH++
is secreted in greater amounts
♥This leaves less KK++
than usual excreted
♥The 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+

45
♥A relative increase in hydrogen ions
results in acidosisacidosis
ACIDOSISACIDOSIS
H+
OH-

46
♥A relative increase in bicarbonate
results in alkalosisalkalosis
ALKALOSISALKALOSIS
H+
OH-

47
♥AlkalosisAlkalosis
H+
OH-
♥AcidosisAcidosis
H+
OH-

48
♥Normal ratio of HCOHCO33
--
to HH22 COCO33 is 20:1
♠HH22 COCO33 is source of HH++
ions in the body
♥Deviations from this ratio are used to identify
Acid-BaseAcid-Base imbalances
BASE ACID
H2CO
H+
HCO3

49
♥AcidosisAcidosis and AlkalosisAlkalosis can arise in two
fundamentally different ways:
♠1) Excess or deficit of CO1) Excess or deficit of CO22
((Volatile AcidVolatile Acid))
♦Volatile AcidVolatile Acid can be eliminated by
the respiratory system
♠2) Excess or deficit of2) Excess or deficit of Fixed AcidFixed Acid
♦Fixed AcidsFixed Acids cannot be
eliminated by the
respiratory system

50
♥Normal values of bicarbonate
(arterial)
♠pHpH = 7.4
♠PCOPCO22 = 40 mm Hg
♠HCOHCO33
--
= 24 meq/L

51
ACIDOSISACIDOSIS
♥A decrease in a normal 20:1 base to
acid ratio
♠An 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
ACI BAS

52
ALKALOSISALKALOSIS
♥An increase in the normal 20:1 base to
acid ratio
♠A 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
ACI BAS

53
SOURCES OFSOURCES OF
HYDROGEN IONSHYDROGEN IONS
C C C C C C
H H H H H H
HHHHHH

54
SOURCES OF HYDROGENSOURCES OF HYDROGEN
IONSIONS
♥1) Cell Metabolism (CO1) Cell Metabolism (CO22 ))
♥2) Food Products2) Food Products
♥3) Medications3) Medications
♥4) Metabolic Intermediate by-4) Metabolic Intermediate by-
productsproducts
♥5) Some Disease processes5) Some Disease processes

55
IONSIONS
♥1) Cellular Metabolism1) Cellular Metabolism of
carbohydrates release COCO22 as a waste
product
♠Aerobic respiration
CC66 HH1212 OO66  COCO22 + H+ H22 O + EnergyO + Energy

56
IONSIONS
♥COCO22 diffuses into the bloodstream where
the reaction:
COCO22 + H+ H22 O HO H22 COCO33
HH++
+ HCO+ HCO33
--
♥This process occurs in red blood cells
♠HH22 COCO33 (carbonic acid)
♠Acids produced as a result of the
presence of COCO22 is
referred to as a
Volatile acidVolatile acid

57
IONSIONS
♥Dissociation of HH22 COCO33 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+
p
H
p
H

58
CARBON DIOXIDE DIFFUSIONCARBON DIOXIDE DIFFUSION
COCO22
COCO22
Red Blood CellRed Blood Cell
SystemicSystemic
CirculationCirculation
COCO22 HH22 OO HH++
HCOHCO33
--
++ ++
HCOHCO33
--
ClCl--
(Chloride(Chloride
Shift)Shift)
COCO22 diffuses into plasma and into RBCdiffuses into plasma and into RBC
Within RBC, the hydration of COWithin RBC, the hydration of CO22 isis
catalyzed by carbonic anhydrasecatalyzed by carbonic anhydrase
Bicarbonate thus formed diffuses intoBicarbonate thus formed diffuses into
plasmaplasma
carboniccarbonic
anhydraseanhydrase
TissuesTissues
PlasmaPlasma

59
COCO22
Red Blood CellRed Blood Cell
Systemic CirculationSystemic Circulation
HH22 OO
HH++
HCOHCO33
--
carboniccarbonic
anhydraseanhydrase
PlasmaPlasma
COCO22 COCO22
COCO22 COCO22 COCO22 COCO22
COCO22
Click for
Carbon
Dioxide
diffusion
++ ++
TissuesTissues
HH++
ClCl--
HbHb
HH++
is buffered byis buffered by
HemoglobinHemoglobin

60
IONSIONS
♥2) Food products2) Food products
♠Sauerkraut
♠Yogurt
♠Citric acid in fruits

61
IONSIONS
♥3) Medications3) Medications
♠May stimulate
HClHCl production
by parietal cells
of the stomach

62
IONSIONS
♥4) Metabolic4) Metabolic
IntermediateIntermediate
by-productsby-products
♠Lactic acid
♠Pyruvic acid
♠Acetoacetic acid
♠Fatty acids
CC66 HH1212 OO66 22

63
IONSIONS
♥Inorganic acids can also be produced
during breakdown of nutrients
♠ProteinsProteins (meat products)
♦Breakdown leads to
productions of sulfuric
acid and phosphoric acid
♠FruitsFruits and VegetablesVegetables
♦Breakdown produces
bases which can help
to equalize acid
production

64
IONSIONS
♥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

65
SOURCES OFSOURCES OF
BICARBONATE IONSBICARBONATE IONS

66
SOURCES OF BICARBONATESOURCES OF BICARBONATE
IONSIONS
♥1) CO1) CO22 diffusion into red blooddiffusion into red blood
cellscells
♥2) Parietal cell2) Parietal cell
secretion of thesecretion of the
gastric mucosagastric mucosa

67
1) CO1) CO22 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-
Red Blood
Cell
Cl-

68
COCO22
COCO22
Red Blood CellRed Blood Cell Systemic CirculationSystemic Circulation
COCO22 HH22 OO HH++
HCOHCO33
--
++ ++
HCOHCO33
--
ClCl--
(Chloride(Chloride
Shift)Shift)
COCO22 diffuses into the plasma and intodiffuses into the plasma and into
the RBCthe RBC
Within the RBC, the hydration of COWithin the RBC, the hydration of CO22 isis
catalyzed by carbonic anhydrasecatalyzed by carbonic anhydrase
carboniccarbonic
anhydraseanhydrase
TissuesTissues
PlasmaPlasma

69
BICARBONATE DIFFUSIONBICARBONATE DIFFUSION
Red Blood CellRed Blood Cell Pulmonary CirculationPulmonary Circulation
COCO22 HH22 OO HH++
HCOHCO33
--
++ ++
HCOHCO33
--
ClCl--
AlveolusAlveolus
PlasmaPlasma
COCO22
Bicarbonate diffuses back into RBC inBicarbonate diffuses back into RBC in
pulmonary capillaries and reacts withpulmonary 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 CO22 and waterand water

70
BICARBONATE DIFFUSIONBICARBONATE DIFFUSION
Red Blood CellRed Blood Cell Pulmonary CirculationPulmonary Circulation
COCO22 HH22 OO
HH++
++ ++
HCOHCO33
--
ClCl--
AlveolusAlveolus
PlasmaPlasma
COCO22
COCO22 HH22 OO

71
2) PARIETAL CELL2) PARIETAL CELL
SECRETIONSECRETION
♥Bicarbonate
ions diffuse into
the bloodstream
to maintain
electrical
neutrality in the
parietal cell
Bloo
d
Lumen
of
Stomac
h
Parieta
l Cells
H+
Cl-
HCO3
-
HCl
Click to see
ion movement
CO2 +
H2O
♥Secrete hydrogen ions into the lumen of
the stomach

72
PANCREATIC CELLPANCREATIC CELL
SECRETIONSECRETION
Bloo
d
Pancreati
c
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
-

73
PARIETAL CELL SECRETIONPARIETAL CELL SECRETION
♥If the two processes are balanced, there
is no net change in the amount of
bicarbonate in blood
♠Loss of gastric or pancreatic juice
can change that balance
HCO3
-
HCO3HCO3
HCO3
-
HCO3
-
HCO3
-

74
♥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 SECRETION
Parietal cells of
gastric mucosa
Pancreatic
epithelial cells
HCO3
-
H+
HCO3
-
H+
lumen of
stomach
pancreatic
juice
blood
blood

75
ACIDOSIS /ACIDOSIS /
ALKALOSISALKALOSIS

76
♥Deviations from normal Acid-Base
status are divided into fourfour general
categories, depending on the source
and direction of the abnormal change in
HH++
concentrations
♠Respiratory AcidosisRespiratory Acidosis
♠Respiratory AlkalosisRespiratory Alkalosis
♠Metabolic AcidosisMetabolic Acidosis
♠Metabolic AlkalosisMetabolic Alkalosis

77
♥Acidosis and Alkalosis are categorized
as MetabolicMetabolic or RespiratoryRespiratory
depending on their primary cause
♠Metabolic AcidosisMetabolic Acidosis andand MetabolicMetabolic
AlkalosisAlkalosis
♦caused by an imbalance in the
production and excretion of acids or
bases by the kidneys
♠Respiratory Acidosis and
Respiratory Alkalosis
♦caused primarily by lung or
breathing disorders

78
ACIDOSISACIDOSIS
♥A 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/liter
Bicarbonat
e
Carbonic
Acid
Bicarbonat
eBicarbonat
eBicarbonat
eBicarbonat
eBicarbonat
eBicarbonat
eBicarbonat
Bicarbonat
eBicarbonat
eBicarbonat
eBicarbonat
e Bicarbonat
eBicarbonat
eBicarbonat
e
Bicarbonat
eBicarbonat
e
Bicarbonat
eBicarbonat
e Bicarbonat
7.

79
ACIDOSISACIDOSIS
♥Acidosis 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+
p=

80
ACIDOSISACIDOSIS
♥May be caused by:
♠An increase in H2CO3
♠A decrease in HCO3
-
♥Both lead to a decrease in the ratio of
20:1
H2CO HCO3
-

81
ACIDOSISACIDOSIS
♥1) Respiratory Acidosis1) Respiratory Acidosis
♥2) 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+

82
H+
H+
H+
H+
H+
H+
H+
H+
H+
H+
H+
H+
H+
H+
H+
H+
♥1) Respiratory alkalosis1) Respiratory alkalosis
♥2) Metabolic alkalosis2) Metabolic alkalosis
ALKALOSISALKALOSIS

83
RESPIRATORYRESPIRATORY
ACIDOSISACIDOSIS

84
RESPIRATORY ACIDOSISRESPIRATORY ACIDOSIS
♥Caused by hypercapnia due to
hypoventilation
♠Characterized by a pH decrease
and an increase in COCO22
CO2 CO2
CO2
CO2
CO2
CO2
CO2
CO2
CO2
CO2
CO2 CO2
CO2
p
H
p
H

85
HYPOVENTILATIONHYPOVENTILATION
♥Hypo = “Under”
Elimination of
CO2
H+
pH

86
♥HypercapniaHypercapnia is defined as an
accumulation of carbon dioxide in
extracellular fluids
CO2 CO2
CO2
CO2
CO2
CO2
CO2
CO2
CO2
CO2
CO2 CO2
CO2
p
H
p
H

87
♥Hypercapnia is the underlying cause of
Respiratory AcidosisRespiratory Acidosis
♠Usually the result of decreased COCO22
removal from the lungs
CO2 CO2
CO2
CO2
CO2
CO2
CO2
CO2
CO2
CO2
CO2 CO2
CO2
p
H
p
H

88
♥The 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

89
♥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

90
♥Respiratory 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

91
♥The treatment of respiratory acidosis
aims to improve the function of the lungs
♥Drugs to improve breathing may help
people who have lung diseases such as
asthma and emphysema

92
♥ Decreased COCO22 removal
can be the result of:
1)1) Obstruction of airObstruction of air
passagespassages
2)2) DecreasedDecreased
respirationrespiration
(depression of(depression of
respiratoryrespiratory
centers)centers)
3)3) Decreased gasDecreased gas
exchangeexchange betweenbetween
pulmonarypulmonary

93
♥1) Obstruction of air passages1) Obstruction of air passages
♠Vomit, anaphylaxis, tracheal cancer

94
♥2) Decreased Respiration2) Decreased Respiration
♠Shallow, slow breathing
♠Depression of the respiratory centers in the
brain which control breathing rates
♦Drug overdose

95
♥3)3) DecreasedDecreased
gas exchangegas exchange
betweenbetween
pulmonarypulmonary
capillaries andcapillaries and
air sacs ofair sacs of
lungslungs
♠Emphysema
♠Bronchitis
♠Pulmonary
edema

96
♥4)4) Collapse of lungCollapse of lung
♠Compression injury, open thoracicCompression injury, open thoracic
woundwound
Left lung
collapsed

97
-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

98
- 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
-

99
-breathing is suppressed holding CO2 in body
-pH = 7.1
H 2
CO
3
HCO3
-
2 20:
CO
2
CO
2
CO
2
CO
2

100
BODY’S COMPENSATION
-kidneys conserve HCO3
-
ions to restore the
normal 40:2 ratio (20:1)
-kidneys eliminate H+
ion in acidic urine
H2
CO
3
HCO3
-
2 30:
HCO3
-
H2CO
3
HCO
3
-
H+
+
acidic
urine

101
- 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
Lactat
e
LIVE
R
HCO3
-

102
ALKALOSISALKALOSIS

103
RESPIRATORY ALKALOSISRESPIRATORY ALKALOSIS
♥Normal 20:1 ratio is increased
♠pH of blood is above 7.4
H2CO
3
HCO3
-
1 20:
= 7.4
H2 CO
3
HCO3-
0.
5
20:
= 7.4

104
♥Cause 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++
CO
2
CO
2
CO
2
CO
2
CO
2 CO
2
CO
2
CO
2
CO
2
CO
2
CO
2
CO
2

105
HYPERVENTILATIONHYPERVENTILATION
♥Hyper = “Over”
Elimination of
CO2
H+
pH

106
♥Can be the result of:
♠1) Anxiety, emotional
disturbances
♠2) Respiratory center
lesions
♠3) Fever
♠4) Salicylate poisoning
(overdose)
♠5) Assisted respiration
♠6) High altitude (low
PO2)

107
♥Anxiety is an emotional
disturbance
♥The most common
cause of
hyperventilation, and
thus respiratory
alkalosis, is anxiety

108
♥Usually the only treatment needed is to
slow down the rate of breathing
♥Breathing into a paper bag or holding
the breath as long as possible may help
raise the blood COCO22 content as the
person breathes carbon dioxide
back in after breathing it out

109
♥Respiratory centerRespiratory center
lesionslesions
♠Damage to brainDamage to brain
centers responsiblecenters responsible
for monitoringfor monitoring
breathing ratesbreathing rates
♦TumorsTumors
♦StrokesStrokes

110
♥FFeverever
♠Rapid shallowRapid shallow
breathing blows offbreathing blows off
too muchtoo much COCO22

111
♥Salicylate poisoningSalicylate poisoning
(Aspirin overdose)(Aspirin overdose)
♠Ventilation isVentilation is
stimulated withoutstimulated without
regard to the status ofregard to the status of
OO22 ,, COCO22 oror HH++
in thein the
body fluidsbody fluids

112
♥Assisted RespirationAssisted Respiration
♠Administration ofAdministration of COCO22 in the exhaledin 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

113
♥High AltitudeHigh Altitude
♠Low concentrations ofLow concentrations of OO22 in the arterialin the arterial
blood reflexly stimulates ventilation in anblood reflexly stimulates ventilation in an
attempt to obtain moreattempt to obtain more OO22
♠Too muchToo much COCO22 is “blown off” in theis “blown off” in the
processprocess

114
♥Kidneys compensate by:
♠Retaining hydrogen ionsRetaining hydrogen ions
♠Increasing bicarbonateIncreasing bicarbonate
excretionexcretion
H+
HCO3
-
HCO3
-
HCO3
-
HCO3
-
HCO3
-
HCO3
-
HCO3
-
HCO3
-
HCO3
-
HCO3
-
H+
H+
H+
H+
H+
H+
H+
H+
H+
H+

115
♥Decreased COCO22 in the lungs will
eventually slow the rate of breathing
♠Will permit a normal amount of
COCO22 to be retained in the lung

116
-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
metabolic balance
- HCO3
-
ions replaced by Cl-
ions

117
-metabolic balance before onset of alkalosis
-pH = 7.4
H2CO
3
HCO3
-
1 20:
HCO3
-
: Bicarbonate Ion
(Na+
) HCO3
-
(K+
) HCO3
-
(Mg++
) HCO3
-
(Ca++
) HCO3
-

118
-respiratory alkalosis
-pH = 7.7
-hyperactive breathing “ blows off ” CO2
H2 CO
3 HCO3-
0.5 20:
CO2
CO2 + H2O

119
BODY’S COMPENSATION
ions and eliminate HCO3
-
in
alkaline urine
H2 CO
3
HCO3
-
0.5 15:
HCO3
-
Alkaline
Urine

120
- therapy required to restore metabolic balance
- HCO3
-
ions
H2CO
3
HCO3
-
0.5 10:
Cl
-
Chloride
containin
g solution

121
COCO22 + H+ H22 OO HH22 COCO33 HH++
++
HCOHCO33
--
Respiratory
Acidosis
Respiratory
Alkalosis

122
METABOLIC ACIDOSISMETABOLIC ACIDOSIS
♥Occurs when there is a decrease in the
normal 20:1 ratio
♠Decrease in blood pHpH and
bicarbonate level
♥Excessive HH++
or decreased HCOHCO33
--
H2CO
3
HCO3
-
1 20:
= 7.4
H 2
CO
3
HCO3
-
1 10:
= 7.4

123
♥Any acid-base
imbalance not
attributable to COCO22 is
classified as
metabolic
♠Metabolic
production of
AcidsAcids
♠Or loss of BasesBases

124
♥If an increase in acid overwhelms the
body's pHpH buffering system, the blood can
become acidic
♥As the blood pHpH drops,
breathing becomes
deeper and faster as the
body attempts to rid the
blood of excess acid by
decreasing the amount
of carbon dioxide

125
♥Eventually, 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

126
♥Metabolic acidosis is always
characterized by a reduction in plasma
HCOHCO33
--
while COCO22 remains normal
HCO3
-
CO2
Plasma
Levels

127
♥Acidosis results from excessive loss of
HCOHCO33
--
rich fluids from the body or from an
accumulation of acids
♠Accumulation of non-carbonic plasma
acids uses HCOHCO33
--
as a buffer for the
additional HH++
thus reducing HCOHCO33
--
levels
tic
d
Muscle
Cell

128
♥The causes of metabolic acidosis can be
grouped into fivefive major categories
♠1)1) Ingesting an acid or a substance
that is metabolized to acid
♠2) Abnormal Metabolism2) Abnormal Metabolism
♠3) Kidney Insufficiencies3) Kidney Insufficiencies
♠4) Strenuous Exercise4) Strenuous Exercise
♠5) Severe Diarrhea5) Severe Diarrhea

129
♥1) 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 overdose
of aspirin (acetylsalicylic acid)
can cause metabolic acidosis

130
♥2) Abnormal Metabolism2) Abnormal Metabolism
♠The body can produce excess acid as
a result of several diseases
♦One of the most significant is Type I
Diabetes Mellitus

131
♥Unregulated
diabetes mellitus
causes
ketoacidosisketoacidosis
♠Body metabolizes
fat rather than
glucose
♠Accumulations of
metabolic acids
(Keto Acids)(Keto Acids)
cause an increase
in plasma HH++

132
♥This leads to excessive production of
ketones:ketones:
♠AcetoneAcetone
♠Acetoacetic acidAcetoacetic acid
♠B-hydroxybutyric acidB-hydroxybutyric acid
♥Contribute excessive numbers of
hydrogen ions to body fluids
Acetone
Acetoacetic
acid
Hydroxybutyric
acid
H+
H+
+
H+
H+
H+
H+

133
♥2) 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

134
♥3)3) KidneyKidney
InsufficienciesInsufficiencies
♠Even the production
of normal amounts of
acid may lead to
acidosis when the
kidneys aren't
functioning normally

135
♥3) Kidney3) Kidney
InsufficienciesInsufficiencies
♠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

136
♥3) 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

137
♥4) 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

138
♥5) 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

139
♥5) 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

140
♥Treating the underlying cause of metabolic
acidosis is the usual course of action
♠For example, they may control diabetes
with insulin or treat poisoning by
removing the toxic substance
from the blood
♠Occasionally
dialysis is needed
to treat severe
overdoses and
poisonings

141
♥Metabolic acidosis may
also be treated directly
♠If the acidosis is mild,
intravenous fluids and
treatment for the
underlying disorder may
be all that's needed

142
♥When acidosis is severe,
bicarbonate may be given
intravenously
♠Bicarbonate provides
only temporary relief
and may cause harm

143
- 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
- hyperactive breathing to “
blow off ” CO2
- kidneys conserve HCO3
-
and
eliminate H+
ions in acidic urine
metabolic balance
- lactate solution used in therapy
is
converted to bicarbonate ions
0.5 10

144
-metabolic balance before onset of
acidosis
-pH 7.4
HCO3
-
: Bicarbonate Ion
(Na+
) HCO3
-
(K+
) HCO3
-
(Mg++
) HCO3
-
(Ca++
) HCO3
-
H2CO
3
HCO3
-
1 20:

145
-HCO3
-
decreases because of excess
presence of ketones, chloride or organic
ions
H 2
CO
3
HCO3
-
1 10:
= 7.4

146
BODY’S
COMPENSATION- hyperactive breathing to “ blow off ”
CO2- kidneys conserve HCO3
-
and eliminate
H+
ions in acidic urine
H2
CO
3
HCO 3
-
0.75 10:
CO2
COCO22 ++
HH22 OO
HCO3
-
+
H+
HCOHCO33
--
++
HH++
Acidic
urine

147
- therapy required to restore metabolic
balance
- lactate solution used in therapy is
converted to bicarbonate ions in the
H2CO
3
HCO3
-
0.5 10:
Lactat
e
Lactate
containin
g solution

148
METABOLICMETABOLIC
ALKALOSISALKALOSIS

149
METABOLIC ALKALOSISMETABOLIC ALKALOSIS
♥Elevation of pHpH due to an increased
20:1 ratio
♠May 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

150
♥A 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
--

151
♥Treatment 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

152
♥Can be the result of:
♠1) Ingestion of Alkaline1) Ingestion of Alkaline
SubstancesSubstances
♠2) Vomiting ( loss of HCl )2) Vomiting ( loss of HCl )

153
♥1) Ingestion of Alkaline1) Ingestion of Alkaline
SubstancesSubstances
♠Influx of NaHCONaHCO33

154
♥Baking soda (NaHCONaHCO33) often used as a
remedy for gastric hyperacidity
♠NaHCONaHCO33 dissociates to NaNa++
and
HCOHCO33
--

155
♥Bicarbonate 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++

156
♥Commercially prepared alkaline
products for gastric hyperacidity are not
absorbed from the digestive tract and do
not alter the pHpH status of the plasma

157
♥2) Vomiting (abnormal loss of2) Vomiting (abnormal loss of
HCl)HCl)
♠Excessive loss of H+

158
♥Gastric juices contain large amounts of
HClHCl
♥During HClHCl secretion, bicarbonate is
added to the plasma
K+ H+
Cl-
HCO3
-
HC
l
Click to
View Animation

159
HC
l
K+
H+
Cl-
HCO3
-
Click to
View Animation
♥The bicarbonate is neutralized as HClHCl is
reabsorbed by the plasma from the
digestive tract
H2CO
3

160
HC
l
K+
HCO3
-
Click to
View Animation
♥During vomiting HH++
is lost as HClHCl and the
bicarbonate is not neutralized in the plasma
♠Loss of HClHCl increases the plasma
bicarbonate and thus results in an increase
in pHpH of the blood
Bicarbonate notBicarbonate not
neutralizedneutralized

161
♥Reaction of the body to alkalosis is to
lower pHpH by:
♠Retain CO2 by decreasing breathing
rate
♠Kidneys increase the retention of HH++
CO
2
CO2
H+
H+
H+
H+

162
- 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
- breathing suppressed to hold
CO2- kidneys conserve H+
ions and
eliminate HCO3
-
in alkaline urine
metabolic balance
- HCO3
-
ions1.2
5
25

163
- metabolic balance before onset of
alkalosis
- pH = 7.4
HCO3
-
: Bicarbonate Ion
(Na+
) HCO3
-
(K+
) HCO3
-
(Mg++
) HCO3
-
(Ca++
) HCO3
-
H2CO
3
HCO3
-
1 20:

164
- pH = 7.7
- HCO3
-
increases because of loss of
chloride ions or excess ingestion of
HCO3-
1 40:
H2 CO
3

165
H2CO
3
HCO3
-
BODY’S
COMPENSATION- breathing suppressed to hold CO2
ions and
eliminate HCO3
-
in alkaline urine
1.25 30
CO2 +
H2O
HCO3
-
+
H+
HCO3
-
H+
+
Alkaline
urine
:

166
- Therapy required to restore metabolic
balance- HCO3
-
ions
H2CO
3
HCO3
-
1.25 25:
Cl-
Chloride
containin
g solution

167
ACIDOSISACIDOSIS
decreased
removal of
CO2 from
lungs
failure of
kidneys to
excrete
acids
metabolic
acid
production
of keto acids
absorption of
metabolic acids
from GI tract
prolonged
diarrhea
accumulation
of CO2 in blood
accumulation
of acid in blood
excessive loss
of NaHCO3
from blood
metabolic
acidosis
deep
vomiting
from
GI tract
kidney
disease
(uremia)
increase in
plasma H+
concentrati
on
depression of
nervous system
accumulation
of CO2 in blood
accumulation
of acid in blood
excessive loss
of NaHCO3
from blood
respiratory
acidosis

168
ALKALOSISALKALOSIS
respiratory
alkalosis
anxiety overdose
of certain
drugs
high
altitudes
prolonged
vomiting
ingestion of
excessive
alkaline drugs
excess
aldosterone
hyperventilati
on
loss of CO2
and
H2CO2 from
blood
loss of acid accumulation
of base
metabolic
alkalosis
decrease
in plasma
H+
concentrati
on
overexcitability
of nervous
system
hyperventilati
on
loss of CO2
and
H2CO2 from
blood
loss of acid accumulation
of base

169
ACID – BASE DISORDERSACID – BASE DISORDERS
Clinical 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

170
RESPONSES TO:RESPONSES TO:
ACIDOSIS AND ALKALOSISACIDOSIS AND ALKALOSIS
♥Mechanisms protect the body against
life-threatening changes in hydrogen
ion concentration
♠1) Buffering Systems in Body1) Buffering Systems in Body
FluidsFluids
♠2) Respiratory Responses2) Respiratory Responses
♠3) Renal Responses3) Renal Responses
♠4) Intracellular Shifts of Ions4) Intracellular Shifts of Ions

171
1)1) Buffer SystemsBuffer Systems
2) Respiratory Responses2) Respiratory Responses
3) Renal Responses3) Renal Responses
4) Intracellular Shifts of Ions4) Intracellular Shifts of Ions

172
BUFFERSBUFFERS
♥Buffering systems provide an immediate
response to fluctuations in pHpH
♠1) Phosphate1) Phosphate
♠2) Protein2) Protein
♠3) Bicarbonate Buffer System3) Bicarbonate Buffer System

173
BUFFERSBUFFERS
♥A buffer is a combination of chemicals in
solution that resists any significant
change in pHpH
♥Able to bind or release free HH++
ions

174
BUFFERSBUFFERS
♥Chemical buffers are able to react
immediately (within milliseconds)
♥Chemical buffers are the first line of
defense for the body for fluctuations in pHpH

175
♥1) Phosphate buffer system1) Phosphate buffer system
Na2HPO4 + H+
NaH2PO4 + Na+
♠Most important in the intracellular
system
PHOSPHATE BUFFERPHOSPHATE BUFFER
SYSTEMSYSTEM
H+
Na2HPO
4
+
NaH2PO
4
Click to
animate
Na++

176
Na2HPO4 + H+
NaH2PO4 + Na+
♥Alternately switches NaNa++
with HH++
SYSTEMSYSTEM
H+
Na2HPO
4
+
NaH2PO
4
Click to
animate
Na++
Disodium hydrogen
phosphate

177
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
SYSTEMSYSTEM
Na2HPO
4 Na2HPO
4Na2HPO

178
♥Regulates pHpH within the cells and the
urine
♠Phosphate concentrations are higher
intracellularly and within the kidney
tubules
♠Too low of a
concentration in
extracellular fluid
to have much
importance as an
ECFECF buffer system
SYSTEMSYSTEM
HPO4
-
2

179
PROTEIN BUFFER SYSTEMPROTEIN BUFFER SYSTEM
♥2) Protein Buffer System2) Protein Buffer System
♠Behaves as a buffer in both plasma
and cells
♠Hemoglobin is by far the most
important protein buffer

180
♥Most important
intracellular buffer
(ICFICF)
♥The most plentiful
buffer of the body

181
♥Proteins 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

182
♥Hemoglobin buffers HH++
from
metabolically produced COCO22 in the
plasma only
♥As hemoglobin releases OO22 it gains a
great affinity for HH++
HH
bb
O2
O2 O2
O2

183
♥HH++
generated at the tissue level from the
dissociation of HH22 COCO33 produced by the
addition of COCO22
♥Bound HH++
to HbHb (Hemoglobin) does not
contribute to the acidity of blood
HH
bb
O2
O2 O2
O2

184
♥As 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 HH22 OO combines with
HCOHCO33
--
HCOHCO33
--
HH22 COCO33 COCO22 (exhaled)
HH
bb
O2
O2 O2
H+

185
♥Venous 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

186
Pr -
added H+
+ Pr -
♥Proteins can act as a buffer for both
acids and bases
♥Protein buffer system works
instantaneously making it the most
powerful in the body
♥75% of the body’s buffer capacity is
controlled by protein
♠Bicarbonate and phosphate buffer
systems require several hours to be
effective

187
♥Proteins 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
-
-
-
- - - -
-
-
-
-
-
-
--------
-
---
-
-
-
-
- - - -
+
+
++
+
+
+
+
+
+
+
+
+
++ +
+
+
+
+
+
+
+ +
+

188
♥H+
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+

189
♥OH-
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-

190
-
-
-
- - - -
-
-
-
-
-
-
--------
-
---
-
-
-
-
- - - -
+
+
++
+
+
+
+
+
+
+
+
+
++ +
+
+
+
+
+
+
+ +
+
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+

191
BICARBONATE BUFFERBICARBONATE BUFFER
SYSTEMSYSTEM
♥3) Bicarbonate Buffer System3) Bicarbonate Buffer System
♠Predominates in extracellular fluid (ECFECF)
HCOHCO33
--
+ added H+ added H++
HH22 COCO33
HCOHCO33
--
HH22 COCO33

192
SYSTEMSYSTEM
♥This system is most important because
the concentration of both components can
be regulated:
♠Carbonic acidCarbonic acid by the respiratory
system
♠BicarbonateBicarbonate by the renal system

193
SYSTEMSYSTEM
♥HH22 COCO33 HH++
+ HCO+ HCO33
--
♠Hydrogen ions generated by metabolism
or by ingestion react with bicarbonate
base to form more carbonic acid
HCOHCO33
--
HH22 COCO33

194
SYSTEMSYSTEM♥Equilibrium shifts toward the formation of
acid
♠Hydrogen ions that are lost (vomiting)
causes carbonic acid to dissociate
yielding replacement HH++
and bicarbonate
HH++ HCOHCO33
--
HH22 COCO33

195
Loss of HCl
Addition of lactic
acid
SYSTEMSYSTEM
HH++
HCOHCO33
--
HH22 COCO33HH22
OO
COCO
22
+ ++
Exercis
e
Vomitin
g

196
1) Buffer Systems1) Buffer Systems
2) Respiratory2) Respiratory
ResponsesResponses

197
RESPIRATORY RESPONSERESPIRATORY RESPONSE
♥Neurons in the medulla oblongata and
pons constitute the RespiratoryRespiratory
CenterCenter
♥Stimulation and limitation of respiratory
rates are controlled by the respiratory
center
♥Control is
accomplished by
responding to CO2
and H+
concentrations in
the blood

198
CENTERCENTER
Respiratory centers
Medulla oblongata
Pons

199
CHEMOSENSITIVE AREASCHEMOSENSITIVE AREAS
♥Chemosensitive areas of the respiratory
center are able to detect blood
concentration levels of CO2 and H+
♥Increases in CO2 and H+
stimulate the
respiratory center
♠The effect is to raise
respiration rates
♦But the effect
diminishes in
1 - 2 minutes
CO2
CO
CO2
CO2
CO2
CO2
CO2
CO2Click to increase
CO2

200
CHEMOSENSITIVE AREASCHEMOSENSITIVE AREAS
♥The effect of
stimulating the
respiratory centers
by increased CO2
and H+
is weakened
in environmentally
increased CO2 levels
♥Symptoms may
persist for several
days

201
CHEMORECEPTORSCHEMORECEPTORS
♥Chemoreceptors are also present in
the carotidcarotid and aorticaortic arteries which
respond to changes in partial pressures
of O2 and CO2 or pH
♥Increased levels of
CO2 (low pHpH) or
decreased levels of
O2 stimulate
respiration rates
to increase

202
CHEMORECEPTORSCHEMORECEPTORS
♥Overall compensatory response is:
♠HyperventilationHyperventilation in response to
increased CO2 or H+
(low pHpH)
♠HypoventilationHypoventilation in response to
decreased CO2 or H+
(high pHpH)

203
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

204
3) Renal3) Renal
ResponsesResponses

205
RENAL RESPONSERENAL RESPONSE
♥The 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 Alkalosis
♦Eliminates bicarbonate ions and
retains hydrogen ions

206
ACIDIFICATIOACIDIFICATIO
N OF URINEN OF URINE
BY EXCRETIONBY EXCRETION
OF AMMONIAOF AMMONIA

207
ACIDIFICATION OF URINE BY EXCRETION OFACIDIFICATION OF URINE BY EXCRETION OF
AMMONIAAMMONIA
Capillar
y
Distal Tubule
Cells
Tubular
urine to be
excreted
NH2
H
+
NH3
NH2
H
+
NH3
WHAT
HAPPENS
NEXT?

208
Capillar
y
Distal Tubule
Cells
Tubular
Urine
NH3
Na
+
Cl-
+
H2CO
3
HCO3
-
+
NaCl
NaHCO3
Click Mouse to
Start Animation
NaHCO3
NH3Cl-
H
+
NH4Cl
Click Mouse to
See Animation
Again
Notice the
H+
- Na+
exchange to
maintain
electrical
neutrality
AMMONIAAMMONIA
Dissociation
of carbonic
acid

209
Capillar
y
Distal Tubule
Cells
Tubular
Urine
NH3
Na
+
Cl-
+
H2CO
3
HCO3
-
+
NaCl
NaHCO3
Click Mouse to
Start Animation
NaHCO3
NH3Cl-
H
+
NH4Cl
Click Mouse to
See Animation
Again
Notice the
H+
- Na+
exchange to
maintain
electrical
neutrality
AMMONIAAMMONIA

210
RESPIRATORY / EXCRETORYRESPIRATORY / EXCRETORY
RESPONSERESPONSE
COCO22 + H+ H22 O HO H22 COCO33 HH++
+ HCO+ HCO33
yperventilation removes
HH++
ion concentrations
ypoventilation increases
HH++
ion concentrations
Kidneys eliminate or retai
HH++
or bicarbonate ions

211
4) Intracellular Shifts of4) Intracellular Shifts of
IonsIons

212
HYPERKALEMIAHYPERKALEMIA
♥HyperkalemiaHyperkalemia is generally associated
with acidosis
♠Accompanied by a shift of H+
ions into
cells and K+
ions out of the cell to
maintain electrical neutrality
H+
K+

213
HYPERKALEMIAHYPERKALEMIA
♥Hyperkalemia is an elevated serum K+
♠H+
ions are buffered in cell by proteins
♥Acidosis may cause Hyperkalemia
and Hyperkalemia may cause
Acidosis
H+
K+

214
HYPOKALEMIAHYPOKALEMIA
♥HypokalemiaHypokalemia is generally associated
with reciprocal exchanges of H+
and K+
in
the opposite direction
♠Associated with alkalosis
♥Hypokalemia is a depressed serum K+
H+
K+

215
ELECTROLYTE SHIFTSELECTROLYTE SHIFTS
cell
HH++
KK++
AcidosisAcidosis
Compensatory Response Result
- HH++
buffered intracellularly
- Hyperkalemia
HH++
KK++
cell
AlkalosisAlkalosis
Compensatory Response Result
- Tendency to correct alkalos
- Hypokalemia

216
ENDEND
ACID - BASEACID - BASE
BALANCEBALANCE

Acid base homeostasis

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