Transcript PULMONARY FUNCTION TEST

PULMONARY FUNCTION
TEST
ARTERIAL BLOOD GASES
AND
ACID – BASE BALANCE
Evaluating acid-base disorders
pH
Total C02
PCO2
Measurement of Total CO2
PCO2 electrode to measure the rate of formation
of released of CO2
specimen must be handled anaerobically to
minimized atmosphere losses of CO2 and
HCO3 ( converted to CO2 ) which would cause a
falsely low total CO2 values
The body normally maintains the arterial blood pH
within a very strict range of 7 .35 to 7.45.
This is accomplished through the buffering
capacity of the interaction of the bicarbonate
system, hemoglobin, phosphate, and proteins.
Metabolic processes produce 15 to 20 mmol of
hydrogen ions in the body each day.
The body is capable of functioning with plasma
levels between 36 and 44 mmol/L of hydrogen
ions.
Deviations from this hydrogen ion concentration
cause changes in the rates of chemical
reactions in cells and metabolic processes in
the body.
At concentrations greater than 44 nmol/L,
consciousness is altered, leading to eventual
coma and death.
At concentrations below 36 nmol/L, symptoms of
neuromuscular irritability and tetany are evident,
followed by loss of consciousness and eventual
death.
ACID-BASE BALANCE
a large quantity of acid is ingested in the normal
diet and produced endogenously as a result of
metabolism
13,000 to 20,000 mmol/L of CO2 largely converted
to H2CO3 is formed as a result of oxidation of
carbohydrates, proteins and fats
40 to 60 mmol/L from ketoacids as a result of
incomplete oxidation of lipids, and sulfuric and
phosphoric acid from oxidation of sulfurcontaining amino acids and phosphorouscontaining compounds
HCO3 is a volatile acid because It can be converted
to CO2, which can be excreted by the LUNGS
Other acids are nonvolatile or fixed acids which
must be excreted in the URINE/KIDNEY
Mechanism that maintain the pH of both ECF and
ICF within narrow limits usually 7.35 to 7.45
1. buffering the blood
2. respiration
3. renal
Buffer is a weak acid in solution with its conjugate
base which is in the form of a salt
acid is added to a solution it combines with the
conjugate base to form a weaker acid – result is
a smaller decrease in pH
ECF buffers
1. bicarbonate/carbonic acid
equilibrium = H2O + CO2
H2CO3
H + HC03
2. hemoglobin/erythrocytes
3. plasma proteins
4. plasma phosphate
Henderson-Hasselbalch Equation
Defined as the log expression of the ionization
constant equation of a weak acid,
is used to express mathematically the pH that
is obtained as the components of the buffer system
become altered:
( HCO3 )
pH = pKa + log --------------( H2CO3 )
The pKa of the bicarbonate system is 6.1 and the
carbonic acid concentration may be expressed as
the partial pressure of carbon dioxide (PCO2)
multiplied by the solubility coeffcient or alpha factor
(0.03).
As a result,
the pH is equal to the pKa added to the log of the
ratio of bicarbonate to carbon dioxide.
In the normal pH range of 7.35 to 7.45,
this ratio should be approximately 20:1.
As the bicarbonate level rises or lowers,
the pH will rise or lower in direct proportion.
Conversely, as PCO2 rises or lowers,
pH will be altered in inverse proportion.
Hemoglobin
is the second most important blood buffer owing
to the fact that each Hb molecule contain 38
histidine residues that are able to bind with H
and owing to its relatively high conc. (15g/dL)
Plasma protein
both their free carboxyl and amino grps are able
to bind H
Organic and Inorganic
least important
HPO4/H2PO4
The sum of all buffer in the blood is
Buffer Base
46 to 52 mmol/L
ave value = 49mmol/L
Actual buffer base - Average value
Base Excess = +/- 3mmol/L
Base deficit
negative base excess or
decrease in blood buffering capacity
HC03¯
anionic fraction in serum
dissociation of H2C03 produced from the
formation of CO2 during metabolism
C02 + H20
H2CO3
H + HC03
reconverted to H2C03 dissociate to H + C02
as the blood perfuse the lungs
filtered freely by the kidney but little or no HC03
present in the urine when the diet is acidic
reabsorption PCT = 85%
DCT = 15%
measured directly – titration with acid
indirectly – using measured PC02 and
H in an Henderson
equation
most commonly measured with other combined
form of CO
TOTAL CO2
CO2,
H2CO3, and
Carbamino grp
this value
approximate
the HCO3 very
closely, bec.
89% to 90% of
all the CO2
that can be
liberated from
serum is in the
form of HCO3
The renal system controls the pH by altering the
rates of reabsorption, secretion, and excretion.
The kidney is able to increase either the
excretion or reabsorptiom of hvdrogen ions in
exchange for sodium and potassium ions to maintain
electroneutralitv.
The rate of bicarbonate reabsorption may also be
altered in response to the pH as bicarbonate acts as
a base in the carbonic acid system.
Bicarbonate is exchanged for other anions such as
chloride and phosphate to maintain electroneutrality.
The kidney is also capable of increasing or
decreasing the rate of ammonia (NH3) formation to
either excrete excess hydrogen ions as ammonium
ions (NH4+) in acidosis or conserve hydrogen ions in
alkalosis.
Kidney regulate the hydrogen ion concentration
principally by increasing or decreasing the
bicarbonate ion concentration in the body fluid.
1. reaction for hydrogen ion secretions
2. sodium ion reabsorption
3. bicarbonate ion excretion in the urine
4. ammonia secretion in the tubule
Tubular secretion of Hydrogen ion
occurs in the luminal border of PCT, DCT, Thick
Loop of Henle, and Collecting tubule - secrete
hydrogen ions into the tubular fluid
In collecting tubule secretions can continue until
the concentration of hydrogen ions in the
tubule becomes as much as 900 times that in
the extracellular fluyid or, in other words,
until the pH of the tubular fluids falls to about
4.5 – represent the limit to the ability of the
tubular epithelium to secrete hydrogen ions
The greater the carbon dioxide conc. in the
extracellular fluid, the greater the rate of hydrogen
secretions
1. decrease respiration
2. increase metabolic rate
At normal carbon dioxide conc. – rate of hydrogen
ion secretion = 3.5mmol/minute
About 84% of all the hydrogen ions secreted by the
tubules are secreted in the PCT but the maximun
conc. gradient that can be achieved here is only
three-to four-fold instead of 900-fold that can be
achieved in the collecting tubules. That is, the pH
can be decreased only to about 6.9, 0.5 pH unit
below the normal
Reabsorption of Sodium
sodium ion are reabsorbed at the same time that
hydrogen ions are secreted – one sodium for
each hydrogen ion that is secreted
occurs in the basal and lateral borders of the
epithelial cells
Reabsorption of Bicarbonate Ions
bicarbonate conc. In the extracellular fluid plays
an extremely important role in the acid-base buffer
system – control the extracellular fluid hydrogen ion
conc.
therefore it is important that the tubules help to
regulate the extracellular fluid bicarbonate ion conc.
However the tubule is impermeable to bicarbonate
normally cannot be reabsorbed
In order for it to be reabsorbed the filtered
Bicarbonate has to combined with secreted
Hydrogen in the tubular fluid to form Carbonic Acid
and then dissociate into H20 and CO2 in the tubular
fluid and the CO2 diffuses into the epithelium
(to combine with H20) or – to the extracellular fluid
into the blood to combined with H20 to form
Carbonic Acid and dissociate into Bicarbonate and
Hydrogen ions
became part of the buffering system – this is the
contribution of the kidneys to control the
extracellular hydrogen ion conc.
Renal sources of Bicarbonate
1. from the dissociation of carbonic acid inside the
epithelial cells from the combination of C02 and
H20 under the carbonic anhydrase
the bicarbonate ions produce in this process
diffuses into the peritubular fluid in
combination with sodium ions that has been
absorbed from the tubule
2. from the formation of carbonic acid in the lumen
of the tubule as result of the combination of
filtered bicarbonate and secreted hydrogen ions
Hydrogen Ion secretion = 3.5mmol/minute
Filtration rate of Bicarbonate = 3.49mmol/minute
the difference is = 0.01mmol/minute - excess
hydrogen ions that did not react with filtered
Bicarbonate
Excess Hydrogen – react with other subs. and
excreted into the urine
Hydrogen ions and bicarbonate ions
in the tubular fluid combined with each other to
form CO2 and H20 - they titrate each other
but titration ( 99% occurs in the PCT ) is not
complete because there are always
hydrogen excess ( 0.01mmol/minute ) over
bicarbonate in the tubules
This is the basic mechanism by which the kidney
corrects either acidosis or alkalosis - by incomplete
titration of hydrogen ions against bicarbonate ions,
leaving one or the other of these to pass into the
urine and therefore to be removed from the
extracellular fluid
The ability of both the respiratory and renal systems
to react to acid base disturbances by attempting to
restore the pH to a normal level is termed
compensation.
The respiratory system
is capable of immediate compensatory response
The renal system
may take several days to reach a detectable
level of compensation.
Compensation for ACIDOSIS and ALKALOSIS
Blood buffers
act instantaneously to minimize the change
in pH, their capacity to do is limited
Respiratory compensation is prompt
Renal compensation is gradual and occurs over
three to four day period after the acid-base
imbalance occur
ultimate regulation with regeneration of
Renal correction of alkalosis
decrease in HCO3 ions in the extracellular fluid
Henderson-Hesselbalch equation
ratio of HCO3 to dissolved CO2 increases when
the pH rises into the alkalosis range above 7.4
the effect of this on titration process in the
tubule is to increase the ratio of HCO3 ions
filtered into the tubules to hydrogen ions
secreted – this increase occurs bec. the
high extracellular HCO3 ion
conc. also increases its conc. in
the glomerular filtrate, and the
low CO2 conc. decreases the
secretion of Hydrogen
Since no bicarbonate ions can be reabsorbed
without first reacting with hydrogen ions, all
the excess HCO3 ions pass into the urine and
carry with them sodium ions or other positive
ions
Thus, the effect,
sodium bicarbonate is removed from the
extracellular fluid - this shifts the pH of the
body fluids back in the acid direction –
alkalosis is corrected
Renal correction of acidosis
Increase in bicarbonate ions in the extracellular
fluid
The ratio of the carbon dioxide to bicarbonate ions
in the extracellular fluid increases
the rate of hydrogen ion secretions rises to
a level far greater than the rate of
bicarbonate ion filtration into the tubules –
excess hydrogen ions are secreted into the
tubules and have no bicarbonate ions react
with.
Each time a hydrogen ions is secreted into the
tubules two other effects occur simultaneously
1.HCO3 ions is formed in the tubular epithelial cell
2.Sodium is absorbed from the tubule into the
epithelial cell
Sodium and HCO3 then diffuse together from the
epithelial cell into the peritubular fluid.
Thus the net effect of secreting excess hydrogen
ions into the tubules is to increase the quantity of
sodium bicarbonate in the extracellular fluid
this increases the HCO3 salt portion of the
Bicarbonate Buffering System - shifts all of
buffering in the alkaline direction – increasing
the pH – correcting the acidosis
Tubular Buffers
excess hydrogen ions are secreted into the
tubules, only a small portion of these can be carried
in the free form by the tubular fluid into the urine –
because the maximum hydrogen ion conc that the
tubular system can be achieve correspond to pH 4.5
At normal daily urine flow this hydrogen ion conc
represents only 1% of the daily excretion of excess
hydrogen ions.
To carry excess hydrogen ions into the urine it must
combine with buffers in the tubular fluid to prevent
itself from rising too high – otherwise, the high conc
would limit further secretion by the tubules - bec of
gradient limited
Tubular buffer systems for transport of the
excess hydrogen ions into the urine
1. phosphate buffer
2. ammonia buffer
3. weak buffer – citrate, urate, bicarbonate
Phosphate Buffer System
poorly reabsorbed, HPO4 (4x>)H2PO4
weak buffer in the blood
more powerful buffer in the tubular fluid
HPO4 + H = H2PO4
The net effect increase the NaHCO3 conc in the
extracellular fluid
Ammonia Buffer System
NH3 and NH4 - synthesize by the tubules except
thin Loop of Henle
deamination of glutamine and other amino acid by
glutaminase, glutamate dehydrogenase or both
Importance of ammonium ion transport mechanism
in handling the excess hydrogen ions
1. More NH3 combined with hydrogen more NH3
are produced from the tubular cells and diffuse
into the lumen
2. When hydrogen ions combine with NH3 and the
resulting NH4 then combine with chloride
NH3 ( ammonia ) + H = NH4 ( ammonium ion ) + Cl
excreted into the urine
The net effect is to increase the sodium bicarbonate
conc in the extracellular fluid
Anion Gap
mathematical approximation of the difference
between the anion and cation routinely measured
in serum
Na, K, Cl and HCO3(as total CO2)
unmeasured cations – Ca, Mg = ave 7 mmol/L
unmeasured anions – PO4, SO4, protein and
anion of organic acids = ave 24 mmol/L
Na – (Cl + total CO2) = less than 17mmol/L
if the anion gap exceed 17mmol/L usually
indicate significantly increased conc. of
unmeasured anions
Causes fro this condition are
1. uremia with retentions of fixed acids
anions such as PO4 and SO4
2. ketotic states – DM, alcoholism or
starvation
3. lactic acidosis - shock
► Chloride
Hypochloridemia
1.GIT losses
2.diabetic ketoacidosis
3.mineralocorticoid
excess
4.salt-losing renal dis
5.high serum HCO3
This is a result of
intracellular shift and
increased renal
excretion of Cl in these
conditions
6. low serum Na in
chronic diseases
► Hyperchloridemia
GIT losses – diarrhea
Renal tubular acidosis
Mineralocorticoid
difficiency
4. Ingestions of toxin – methanol, salicylate, ethylene
glycol, and paraldehyde
5. increased plasma proteins - dehydration
6. metabolic alkalosis due to the titration of plasma
proteins resulting in loss of H and the consequent
increase in the net negatively charge proteins
Decreased anion gap ( < 10 mmol/L) can result in
either an
increase in unmeasured cations or a
decrease in unmeasured anions
increased in unmeasured cations
1. Li intoxication
2. hypermagnesemia
3. multiple myeloma
4. polyclonal gammopathy
gamma globulin +charge at physiologic pH
5. polymyxin ( polycationic)B therapy
Decreased unmeasured anions
1. hypoalbuminemia
2. hyponatremia with normal or increased
ECF(SIADH) due to selective renal excretion
of unmeasured anions in this condition.
Some form of acidosis
fall in HCO3 is balanced by an elevation of Cl
owing to loss of HCO3 rich and Cl poor fluid and
retention of dietary Cl – anion gap remains within
normal limits
hyperchloridemic acidosis are associated
with loss of HCO3 through GIT or kidney
Increased anion gap develops in Lactic, Diabetic, or
Uremic or secondary to ingestion of foreign
acids
minimal or slight depression of Cl
Chronic Renal failure
increased anion gap due to retention of PO4 and
The presence or absence of an increase anion gap
is characteristic of certain disorders and is helpful
in diagnosing the underlying etiology of metabolic
acidosis
Increased anion gap in metabolic alkalosis may be
moderately increased owing to hemoconcentration,
increased blood lactate or increased negative
charges on circulating proteins
serum Cl is usually decreased
Modest increased in aniop gap is not diagnostic
When the anion gap exceeds 30mmol/L, the
presence of an organic acidosis is highly likely
In organic acidosis
increase in the blood acid anion conc. parallel
the increase in the anion gap
and both values closely approximate the decrement
in plasma HCO3
AG/HCO3 ratio = > 1 suggest a superimposed
metabolic alkalosis
AG/HCO3 ratio = < 0.8 is consistent with
hyperchloridemic component of acidosis
AG is useful also for quality of laboratory results for
Na, K, and Cl and total CO2
Laboratory Measurement of Acid-Base Parameters
it can evaluate the acid-base status
it can identify the cause
Determine the following
1.pH
2.one or both
total CO2(really the HCO3)
PCO2
3. in addition
AG determination if metabolic acidosis is
present
Renal function studies
that measure the ability of the kidneys
either to excrete an acid load or to
reabsorb an alkali load are useful for
confirming renal tubular diseases
resulting in hypochloridemic acidosis
ACID-BASE IMBALANCES
Acidemia
blood pH of less than 7.35 / H>45nmol/L
result from accumulation of CO2 in the body
Respiratory acidosis result of hypoventilation
or ventilation/perfusion inequalities
Renal compensation – reabsorption of HCO3
reflected by an increase
in total CO2 and in HCO3
also occur from an accumulation of fixed acids
or loss of HCO3 result in a primary decrease
in
total CO2 – Metabolic acidosis
two types
acidemia with an increased AG (>17)
acidemia with normal AG (<17)
hyperchloridemic metabolic acidosis
Respiratory compensation – increase rate
Alkalemia
blood pH greater than 7.45 / H less than 35nmol/L
decreased PCO2 conc. in the blood
Respiratory alkalosis bec. it secondary to
hyperventilation
Renal compensation – decreasing the
reabsorption of HCO3
Total circulating HCO3 is decreased
also occur when there is loss of fixed acids or an
increase in blood alkali such as HCO3
Primary increase in HCO3 – Metabolic
alkalosis
loss of fixed acids due to prolonged
vomiting or to nasogastric suctioning
alkali excess in excessive ingestion of
basic subs., such as antacids
also occur in disease state in which there is
excessive intracellular movement of H from
the extracellular space ( often induced by
hypokalemia) or excess excretion of H into
the urine or both
excess excretion of H
mineralocorticoids – hyperaldosteronism,
Cushing syndrome, or
Prolonged administration of
corticosteroids
Respiratory compensation – decrease rate of
respiration
Mixed Acid-Base Disturbances
respiratory disturbances are frequently associated
with simultaneous metabolic pertubations
these can be detected if the
compensatory response falls short or exceeds
that expected
AG or the ratio change in anion gap to that of
HCO3 (AG/HCO3) is abnormal
Common combinations making H pertubation worse
Respiratory acidosis ad Metabolic acidosis
acute pulmonary edema and cardiorespiratory
arrest – poor tissue perfusion(lactic acidosis) and
pulmonary edema(poor alveolar
ventilation)
Respiratory alkalosis and metabolic alkalosis
vomiting and hyperventilating secondary to such
disturbance as pain or psychogenic stress
Common combination lessening H pertubations
Respiratory acidosis and Metabolic alkalosis
COPD receiving diuretics
Metabolic acidosis and Respiratory alkalosis
CRF and hyperventilation
Metabolic acidosis and Metabolic alkalosis
CRF complicated by severe vomiting or
nasogastric suction
Blood Gases
The process of respiration supplies oxygen
to tissues and removes the carbon dioxide produced
by cellular metabolic activity.
External respiration takes place at the
alveolar surface in the lung where oxygen in the air is
exchanged with carbon dioxide in the blood.
Internal respiration takes place at the body
tissues where oxygen in the blood is delivered to the
cells and carbon dioxide is transferred from the cells
to the blood for disposal.
Regulation of respiration
is carried out through neurochemical mediation.
The medullary respiratory center of the brain
stem is capable of altering the rate and
depth of respiration.
Central chemoreceptors
at the medulla oblongata
respond only to an increased carbon
dioxide level.
Peripheral chemoreceptors
in the carotid bodies and aortic bodies
regulate the medullary respiratory center.
are stimulated by either a decreased
oxygen or an increased carbon dioxide
level
The exchange of gases is dependent on the
partial pressure gradients
at the surfaces of the cells involved in the
exchange.
For example,
at the alveolar surface,
the partial pressure of oxygen in the air is
greater than that in the blood; therefore,
oxygen moves into the blood.
Hemoglobin in the red blood cell is responsible
for transportation of oxygen and carbon dioxide
through the circulatory system.
The oxygen saturation
refers to the amount of hemoglobin that is
saturated with oxygen at the time of
sampling.
The respiratory system controls the body pH through
removal of the waste product of carbon dioxide, a
component of the bicarbonate system.
The chemical reactions of' the bicarbonate
system are as follows:
H20 + CO2
H2CO3
H + HC03
In the tissues,
Hemoglobin picks up a portion of the cellular
carbon dioxide forming carbaminohemoglobin.
The remainder of the carbon dioxide combines
with water to form carbonic acid, which dissociates
to form hydrogen ions and bicarbonate ions.
The hydrogen ions will bind to deoxygenated
hemoglobin and the bicarbonate will move out of the
cell in exchange for chloride moving into the cell,
referred to as the chloride shift.
At the lungs,
the hydrogen ions bound to deoxygenated
hemoglobin are released when oxygen binds the
hemoglobin.
The hydrogen ions then bind to bicarbonate ions
to form carbonic acid, which then forms water and
carbon dioxide that is expired into the air.