15 respiratory acidosis

399

S. Faubel and J. Topf 15 Respiratory Acidosis

1515 Respiratory Acidosis

400

The Fluid, Electrolyte and Acid-Base Companion

Respiratory acidosis is characterized by an increased PCO2 and a decreasedpH. After buffering and renal compensation, the bicarbonate is increased.Increased carbon dioxide, hypercarbia, is always the result of inadequaterespiration.

Carbon dioxide is a waste product of cellular metabolism. Each day, thebody produces approximately 15,000 millimoles of CO2 which needs to beeliminated by the lungs. If the lungs are unable to completely eliminatecarbon dioxide, it accumulates and causes respiratory acidosis.

The study of respiratory acidosis is the study of respiratory insufficiency.

Respiratory acidosis is characterized by an increase in ________which decreases _____.An increase in the arterial carbon dioxide level is _________ due toinadequate respiration.

PCO2pHalways

Introduction!Respiratory acidosis is due to respiratory in-sufficiency.

One could imagine that CO2 levels could rise from increased production. But, healthy lungsare so adept at removing CO2, that no matter how fast CO2 is produced, the lungs are ableto clear it. Only if lung disease is already present can increased production of CO2 causerespiratory acidosis. For example, in patients with chronic pulmonary disease and chroni-cally elevated levels of carbon dioxide, increased metabolic production of CO2 (e.g., sepsis)can further increase PCO2.

pH HCO3

–

CO2

pH HCO3

–

CO2

pH HCO3

–

CO2

pH HCO3

–

CO2

METABOLIC ALKALOSIS

RESPIRATORY ALKALOSISRESPIRATORY ACIDOSIS

METABOLIC ACIDOSIS

401


Overview: Respiration is a four-step process.

CO2 CO2

CO2 O2

O2O2

O2

O2

O2

To fully understand the development of respiratory acidosis, it is important tohave an understanding of respiration. Respiration is the process by which thelungs carry out their primary function of eliminating CO2 and oxygenating theblood.

Respiration occurs in four steps: 1) sensing and signaling 2) muscles andmotion 3) free flow and 4) gas exchange. Inadequate respiration causing respi-ratory acidosis may occur from a defect in one or more of the steps of respira-tion.

The delivery of air to the alveoli is called ventilation. Ventilation encompassesthe first three steps of respiration. Hypoventilation is the inadequate deliv-ery of air to the alveoli resulting in the accumulation of carbon dioxide.

The process of respiration contains four steps: sensing and _________,muscles and motion, free _______ and gas exchange.Gas exchange occurs in the _________.Ventilation encompasses the first _______ steps of respiration.

signalingflow

alveolithree

Muscles and motionThe muscles of respiration expand thechest which lowers intrathoracic pressureand draws air into the lungs.

Sensing and signalingThe respiratory control center in the medullaresponds to changes in CO2, O2 and pH bysending signals via nerves to the musclesof respiration.

Free flowA patent airway is necessary for air to flowinto the alveoli.

Gas exchangeExchange of CO2 and O2 occurs in the al-veoli. Oxygen enters the blood and CO2 en-ters the alveoli.

+

402


Introduction to terms used by pulmonologists, part one.

Alveolar minute ventilation (minute ventilation) is the amount of airdelivered to functioning alveoli each minute. This process is accomplishedin the first three steps of respiration (sensing and signaling, muscles andmotion, and free flow). Normal minute ventilation for an adult ranges fromfour to six liters per minute.

Minute ventilation and PCO2 are inversely related. Increased minute ven-tilation causes carbon dioxide to fall and decreased minute ventilationcauses carbon dioxide to rise.

physiologicdead space

tidalvolume

respiratoryrate

minuteventilation

Tidal volume is the amount ofair inspired in a single breath.Normal tidal volume is be-tween 6 and 8 mL/kg (about500 mL in a 70 kg man).

Physiologic dead space is thevolume of air in the lungs whichdoes not participate in gas ex-change. Physiologic dead spaceis normally 30% of tidal volume,or about 150 mL.

Respiratory rate is the num-ber of breaths per minute andis normally between 12 and 16breaths/min.

alveolar minute ventilation (L/ min)

PCO 2 (

mm

Hg)

CCC

CCCC

CCCCCC

CCCCCCCC

403


CO2

CO2

O2

O2

O2

Physiologic dead space refers to all the areas of the lung where air isdelivered, but gas exchange does not occur. Physiologic dead space is thesum of the anatomic and alveolar dead spaces.

Anatomic dead space. The air passages which bring air intoand out of the alveoli, the conducting airways, are not capable ofgas exchange. The conducting airways are made up of the tra-chea, bronchi and bronchioles. The volume of anatomic deadspace is constant.Alveolar dead space. Some alveoli receive air but do not par-ticipate in gas exchange because they are not perfused with blood.The volume of alveolar dead space varies with disease and bodyposition.

Anatomic dead spaceTrachea, bronchi and bronchi-oles are all examples of ana-tomic dead space.

Alveolar dead spaceAlveoli which are ventilatedbut not perfused are alveolardead space.

Introduction to terms used by pulmonologists, part two.

404


On the following pages, we introduce each of the steps of respiration (sens-ing and signaling, muscles and motion, free flow and gas exchange). Followingeach description, there is a page that lists several diseases associated with thatstep. This is followed by one or two grey pages discussing a specific disorderassociated with that step.

When reading through this for the first time, you may not want to spend toomuch time reading through the details of each disorder. The lists and definitionsare provided primarily as examples and are not exhaustive.

Additionally, keep in mind that respiratory diseases which cause respiratoryacidosis commonly involve a defect in more than one of the steps of respiration.When more than one defect is at fault, we typically list the disorders under theprimary and/or inciting event.

Ready?

405


Sensing and signaling!The first step of respiration is sensingCO2 and O2 and signaling the muscles of respiration.

The unconscious control of breathing resides in the respiratory controlcenter of the medulla. Here, information about CO2 and O2 levels are pro-cessed (sensed) and signals are sent, via nerves, to the muscles of respira-tion. CO2 and O2 are the primary stimuli affecting respiration. Surprisingly,increased CO2 is a stronger stimulus for respiration than decreased O2.

Intracellular alterations in pH, induced by changes in CO2, are sensed bychemoreceptors in the medulla (separate from the respiratory control cen-ter). An increase in PCO2 of only 1 mmHg is sufficient to stimulate respira-tion. Because of this exquisite sensitivity to CO2, arterial PCO2 is normallykept within the narrow range of 36 to 44 mmHg.

Oxygen levels are sensed by chemoreceptors in the carotid bodies locatedat the bifurcation of the internal and external carotid arteries. Hypoxia doesnot stimulate respiration until the PO2 falls below 60 mmHg.

Sensing defects causing respiratory acidosis are typically due to disorderswhich affect the ability of the respiratory control center to respond to increasesin carbon dioxide. Signaling defects are due to diseases which affect the nervesof the respiratory muscles. Specific disorders of sensing and signaling are re-viewed on the following pages.Breathing is controlled in the _________ control center.The respiratory control center regulates ventilation by integratinginformation about _______ _______ levels and O2 levels.

respiratory

carbon dioxide

carotid body

O2

Sensing

Signalingmuscles of respirationnerves

phrenic

intercostal

accessory

C3, C4

diaphragm

intercostal

sternocleidomastoid

scalene

medulla

CO2

RESPIRATORYCONTROLCENTER

406


When PO2 decreases, the carotid bodies trigger the respiratory control centerto increase minute ventilation. Increased minute ventilation causes a decreasein PCO2. The fall in PCO2 is detected in the medulla which suppresses respirationin order to return PCO2 to normal. Only when hypoxemia becomes critical, PO2below 60 mmHg, does the respiratory control center sacrifice tight regulation ofcarbon dioxide in order to increase oxygenation. Thus, carbon dioxide main-tains primary control over minute ventilation unless hypoxia is life-threatening.

Sensing and signaling!Carbon dioxide is the primary regulatorof respiration unless oxygen is too low (PO2 < 60 mmHg).

_______ maintains primary control over minute ventilation until thepartial pressure of oxygen falls below ______ mmHg.Oxygen is essentially ignored by the respiratory __________ centeruntil hypoxia is life-____________.Carbon dioxide levels are detected by pH detectors in the _______,while oxygen is detected by ______________ in the carotid bodies.

PCO260control

threateningmedulla

chemoreceptors

Decreased PO2 is sensed atthe carotid bodies and a signalis sent to the respiratory con-trol center which increasesventilation.

Increased ventilation increas-es PO2 but decreases PCO2

.Decreased PCO2

is detected inthe medulla and ventilation isdecreased.

CC

O2O2

O2

O2

O2

O2

O2 O2O2

O2O2

O2

O2

O2

O2

O2

O2

O2

CCCC

CCCC

Decreased ventilation returnsPCO2 to normal, but returnsoxygen to the initial low level.

407


Sensing and signaling!The causes of sensing and signalingdefects are both central and peripheral.Sensing defectsApnea of prematurity is an almost uni-versal problem associated with prematurebirth. In this disorder, low oxygen and highcarbon dioxide suppress respiration ratherthan stimulate it. While this is maladaptivefor an infant, it is an appropriate responsefor the fetus.In utero, the fetus practices breathing tostrengthen its respiratory muscles in anticipa-tion of life after birth. In utero, however, oxy-gen is supplied by the placenta. When oxygenlevels fall, the fetus stops wasting oxygen bybreathing, shunting oxygen to essential organsand processes.Apnea of prematurity resolves with brain stemmaturation and is treated with caffeine.Brain stem injury from infarction, hemor-rhage, trauma, demyelination or degenerationcan cause respiratory failure by direct damageto the respiratory control center.Central sleep apnea: see page 409.Drugs such as narcotics, ethanol, benzodi-azepines and inhaled anesthetics (with theexception of nitrous oxide) all decrease thesensitivity of the respiratory control center toCO2, inhibiting respiration.Hypothyroidism, when severe, can causehypoventilation from decreased sensitivity ofthe respiratory control center to CO2.Oxygen therapy in patients with chronic CO2retention. See page 408.Obesity hypoventilation syndrome(Pickwickian syndrome) is due to a defectwhich prevents the increase in respiratory ef-fort needed to overcome obesity.Primary alveolar hypoventilation (On-dine’s curse) is a rare condition in which pa-tients do not have an unconscious respiratorydrive. Since conscious control of respiration isintact, the disorder reveals itself only duringsleep. Primary alveolar hypoventilation can betreated with nighttime mechanical ventilation.

Signaling defectsAmyotrophic lateral sclerosis (ALS) is amotor neuron disease characterized by mo-tor neuron destruction. ALS is characterizedby ascending paralysis, muscle atrophy andloss of deep tendon reflexes. Involvement ofthe respiratory nerves results in respiratoryinsufficiency.Lou Gehrig was a baseball player in the earlytwentieth century. He played with Babe Ruthfor the New York Yankees. Mr. Gehrig set amajor league record by playing in over 2000consecutive games. He died in his thirties ofALS which is now commonly referred to as LouGehrig’s disease.Diaphragmatic paralysis can be causedby thoracic trauma, thoracic surgery, multiplesclerosis and muscular dystrophy.Guillain-Barré syndrome is a rapidly pro-gressive paralysis which typically follows anacute viral illness by 1 to 3 weeks. It is charac-terized by ascending muscle weakness, lossof reflexes and a lack of sensory involvement.Respiratory insufficiency and failure occur frominvolvement of the muscles of respiration.About a third of patients require mechanicalventilation. Complete recovery is the norm andmortality is low. Patients may be treated withplasmapheresis or gamma globulins.Guillain-Barré is also known as acute demy-elinating polyneuropathy.Post-polio syndrome is characterized by thedegradation of motor neurons which can oc-cur 20 to 30 years after paralytic polio. Involve-ment of the nerves of respiration can occur.Spinal cord injury at or above the level ofthe origin of the phrenic nerve can cause res-piratory insufficiency or failure. The phrenicnerve is composed of nerves from C3, C4 andC5 (3,4 and 5 keep the diaphragm alive).

408


Clinical correlation: In chronic respiratory acidosis, hypoxia is theprimary stimulus for respiration.

The control of respiration is altered in patients with chronically elevatedcarbon dioxide levels and chronic respiratory acidosis (e.g., COPD). Inthese patients, hypoxemia is the primary stimulus for respiration while in-creases in CO2 have little effect.

In chronic respiratory acidosis, the pH is nearly normal despite a grosslyelevated PCO2. The respiratory control center of the medulla is less sensi-tive to increases in CO2 because of the near-normal pH. If CO2 increasesfurther, the change in pH is less dramatic and produces little change inrespiration. Because the sensitivity to CO2 is lost in patients with chronicrespiratory acidosis, hypoxemia is the primary stimulus for respiration.

The hypoxic drive of respiration is clinically important. The administra-tion of large amounts of oxygen (100% oxygen by mask) removes the hy-poxic respiratory drive and suppresses respiration. The ensuing hypoven-tilation increases CO2 resulting in acidosis, obtunded mental status andrespiratory failure. Therefore, oxygen must be used with caution in patientswith chronic carbon dioxide retention.

medulla

CO2

carotid body

O2

RESPIRATORYCONTROL CENTER

Oxygen is the primary stimu-lus for respiration.

The respiratory control cen-ter is insensitive to CO2.

Chronic respiratory acidosis

409


Clinical correlation: Sleep apnea is a defect in nocturnal res-piration.

Sleep apnea is characterized by arrests in airflow which occur duringsleep. Apneic episodes last at least 10 seconds and occur more than 30times per night. The characteristic symptoms and signs include daytimesomnolence, hypertension, snoring and obesity. An important characteris-tic of all types of sleep apnea is that the hypoxia, hypercarbia and respira-tory acidosis occur only at night. During the day, patients with sleep apneahave normal O2, CO2 and pH.

There are three types of sleep apnea: central, obstructive and mixed. Central sleep apnea is a cerebral disorder which affects the normal

respiratory drive in the medulla. Apneic episodes are characterized by alack of respiratory effort. During apneic episodes, patients become hypoxicand hypercarbic, then awaken, restore normal ventilation and return to sleep.This cycle can recur hundreds of times each night.

Obstructive sleep apnea (OSA) is characterized by collapse of thesoft tissues in the upper airway during sleep. Apneic episodes are charac-terized by respiratory effort that is unable to overcome the obstruction.Breathing is restored when the patient arouses and increased muscle toneclears the obstruction. Loud snoring is an almost universal feature of OSA.Medical management involves weight loss, and the use of a device thatmaintains continuous positive airway pressure (CPAP) in the pharynx andthus stents the soft tissues open. Surgery is an option for patients who failmedical management.

Mixed sleep apnea is characterized by components of both centraland obstructive sleep apnea. Apneic episodes are characterized by thecessation of respiratory effort followed by collapse of the soft tissues andairway obstruction. Respiratory effort then returns, but cannot overcomethe obstruction.

pH, CO2 and O2are normal dur-ing the day.

Apnea occurs at night; CO2increases while pH and O2decrease.

ZZ

ZZ Z

410


Muscles and motion!The second step of respiration is propermovement of the chest wall.

Step two of respiration is muscles and motion which refers to the mechanicalprocess of inspiration and expiration. Inspiration is an active process and expi-ration is a passive process. Inspiration and expiration are controlled by thecontraction and relaxation of the muscles of respiration.

Inspiration is the process by which air is sucked into the lungs. When themuscles of respiration contract, the chest cavity expands, lowering intratho-racic pressure. The difference between the atmospheric and intrathoracic pres-sures draws air into the lungs.

Expiration is a passive process which occurs when the muscles of respirationrelax, the chest wall falls inward and air is forced out. With increased respira-tory effort (e.g., exercise), expiration can become an active process as musclesspeed the contraction of the chest.

When the muscles of respiration contract, the size of the intrathoraciccavity ________ and intrathoracic pressure __________.Muscles and motion is step ______ in the process of respiration.

AAAincreases; decreases

two

InspirationChest wall moves out; air moves in.

ExpirationChest wall moves in; air moves out.

411


The major muscles of respiration are the sternocleidomastoid, scalene,intercostals and diaphragm. When contracted, all serve to expand the intratho-racic cavity and facilitate the movement of air into the lungs.

The sternocleidomastoid and scalene are located in the neck and attach tothe clavicle and first rib. When contracted, these muscles lift the clavicles andthe first ribs to expand the chest cavity upward. The sternocleidomastoid andscalene are accessory muscles of respiration which means they are not essen-tial to the process of respiration, but are important when breathing becomeslabored. The sternocleidomastoid is innervated by the accessory cranial nerve(CN XI) and the scalene muscles are innervated by the inferior cervical nerveplexus (C3, C4).

Intercostal muscles are located between the ribs and join a set of upper andlower ribs. The intercostal muscles raise the chest up and out and are inner-vated by the intercostal nerves (T1-T12).

The diaphragm separates the thoracic and abdominal cavities and is the pri-mary muscle of respiration. It attaches to the lower ribs and moves inferiorlywhen it contracts to expand the chest cavity downward. Innervation is via thephrenic nerve (C3, C4, C5).

SternocleidomastoidAccessory nerve

(CN XI)

DiaphragmPhrenic nerve (C3, C4, C5)

Muscles and motion!The diaphragm, chest wall muscles andmuscles in the neck expand the lungs.

ScaleneThird and fourth cervical nerve(C3, C4)

Intercostal musclesIntercostal nerves(T1 - T12)

Intercostal musclesIntercostal nerves

(T1 - T12)

The __________ is the primary muscle of respiration.The sternocleidomastoid and scalene muscles are known as____________ muscles of respiration.

diaphragm

accessory

412


Muscles and motion!There are many causes of respiratorymuscle dysfunction.Anatomic abnormalities and traumaFlail chest is due to multiple consecutivefractured ribs on a single side of the chest,causing the chest wall to become unstable.During inspiration, the unstable chest wallcollapses inward instead of moving outward.Kyphoscoliosis is a deformity of the spinewhich restricts chest wall expansion during in-spiration.Pneumothorax: see page 413.BotulismBotulinus toxin is produced by the bacte-ria Clostridium botulinum, a gram positiverod. There are three forms of the disease:• food-borne: direct ingestion of toxin due

to improperly canned foods.• wound infection: spores enter a wound

and germinate, releasing toxin; it is associ-ated with trauma.

• infantile: ingestion and germination ofspores in an immature GI tract; it is associ-ated with giving infants honey.

Botulism toxin irreversibly blocks the releaseof acetylcholine from the neuromuscular junc-tion. Death is due to respiratory failure. SeeThe Microbiology Companion for details.DrugsAminoglycoside antibiotics, such as gen-tamicin and tobramycin, can cause muscularweakness at high doses. Muscle weakness isexacerbated by hypermagnesemia. Treatmentconsists of stopping the drug and giving cal-cium.Succinyl choline / vecuronium are depo-larizing agents used for paralysis during sur-gical and medical procedures. These agentsact at the neuromuscular junction.ElectrolytesHypokalemia, hypophosphatemia or hy-permagnesemia, when severe, can causemuscle weakness and respiratory acidosis.

Genetic disordersAcid maltase deficiency is a disorder ofan enzyme involved in the metabolism of gly-cogen into glucose (type 2 glycogen storagedisease). This disorder is associated with theaccumulation of glycogen in muscle cellswhich interferes with contraction. This dis-ease presents in infancy with respiratory in-sufficiency, cardiomegaly and hepatomegaly.Death usually occurs by two years of age.Childhood and adult onset is less common.The childhood form resembles muscular dys-trophy and is associated with elevated CKenzymes. The responsible gene has beenmapped to chromosome 17.Duchenne’s and Becker’s muscular dys-trophy are X-linked recessive disorders whichcause progressive muscle weakness. Patientsare usually asymptomatic at birth but grossmotor control is delayed until late in the firstyear of life. Muscle weakness is progressiveand ultimately compromises respiration.Duchenne’s is more severe with death usuallyoccurring by the third decade of life. BecauseBecker’s causes less severe disease, patientscan live into their forties. The responsible genehas been localized to Xp21.Periodic paralysis is a genetic disorder (au-tosomal dominant in ! of cases and sporadicin ") associated with intermittent episodes ofsevere hypokalemia and muscle weakness.Respiratory involvement is rare, but can befatal. See page 495.Myasthenia gravisMyasthenia gravis is an autoimmune dis-order characterized by the production of anti-bodies against the acetylcholine receptors atthe neuromuscular junction. Prevalence is 1in 10,000. The male:female ratio is 2:3 withmen affected in the 50-70 age range and fe-males in early adulthood. Myasthenia crisis oc-curs when weakness affects the muscles ofrespiration. Crises are treated with anticho-linesterases (pyridostigmine) and plasmapher-esis.

413


Clinical correlation: Pneumothorax can cause respiratory ac-idosis by affecting muscles and motion.

In order to understand how a pneumothorax develops, it is important tounderstand how the lung and chest wall work together. The lung is like aNerf® ball: elastic walls surrounding millions of tiny air pockets which canbe compressed or stretched open. The Nerf® lung has a smooth, shiny sur-face called the visceral pleura. The chest wall, which surrounds the Nerf®

lung, is lined by the parietal pleura. Between the visceral and parietalpleurae is a small amount of fluid. Although there is no solid connectionbetween the visceral and parietal pleurae, surface tension seals the lung tothe chest wall. The surface tension is strong enough that during inspira-tion, when the chest wall expands outward, it also expands the lung.

In a pneumothorax, air gets into the space between the two pleuraebreaking the surface tension which adheres the lung to the chest wall.When the seal between the visceral and parietal pleurae is broken, expan-sion of the chest wall during inspiration does not expand the lung. Withoutthe chest wall to expand it, the lung collapses due to its elasticity. Thecollapse of the lung can shift the trachea toward the pneumothorax.

A tension pneumothorax is more life-threatening than a pneumothoraxbecause the size of the air-filled space between the pleurae enlarges witheach inspiration. During expiration, the air is unable to escape due to aone-way valve effect of the pleural defect. This results in continued airentrapment in the pleural space. The complications of the increasing pleu-ral air are ineffective respiration, hypoxia and decreased venous returnresulting in hemodynamic collapse. In a tension pneumothorax, the struc-tures of the mediastinum (e.g., trachea, heart) shift to the opposite side ofthe pneumothorax. Tension pneumothorax is a medical emergency whichrequires immediate decompression. A 14-gauge needle should be insertedinto the air-filled pleural space in the second or third intercostal space atthe midclavicular line.

PNEUMOTHORAX TENSION PNEUMOTHORAX

second intercostal spacemidclavicular line

airair

air

TREATMENT

visceral pleura parietal pleura

414


Respiration requires the free flow of air through a patent airway. Obstructionat any point in the flow of air to the alveoli can cause respiratory acidosis. Theairway is divided into the upper and lower respiratory tracts.

The upper respiratory tract consists of the nasopharynx and oropharynx.The lower respiratory tract begins at the larynx. In addition to its role in phona-tion, the vocal cords of the larynx protect against the entry of foreign bodies intothe lower respiratory tract.

The lower respiratory tract consists of conducting airways which begin withthe trachea and end with the terminal bronchioles. In the thorax, the tracheadivides into right and left mainstem bronchi which supply the right and left lung.Anatomically, the right mainstem bronchus is a nearly straight continuation ofthe trachea, while the left mainstem bronchus branches off at an abrupt angle.Therefore, the right lung is more commonly involved when foreign materialis aspirated.

The mainstem bronchi branch into secondary bronchi which supply the lobesof the lungs. These bronchi branch into the tertiary bronchi which supply thesegments of each lobe. The tertiary bronchi branch several times into progres-sively smaller airways known as bronchioles. The terminal bronchioles are thesmallest segments of the conducting system; only beyond this point can gasexchange occur.

Free flow!The third step of respiration is the free flow of air intothe alveoli through a patent airway.

Because of the downward angle of the ________ mainstem bron-chus, aspirated material is more likely to affect the _______ lung.

rightright

trachea

oropharynx

bronchi

bronchioles

nasopharynx

415


Free flow!Factors which cause airway obstruction interfere withthe free flow of air into the alveoli.Anatomic obstructionLaryngomalacia and tracheomalacia arecongenital malformations of the airway; bothare characterized by floppy airways whichcollapse on inspiration. The malformationtypically presents in infancy as noisy breath-ing. These disorders can also be a complica-tion of prolonged intubation. Laryngo- andtracheomalacia typically resolve without in-tervention. For severe cases, CPAP or tra-cheostomy may be necessary.AspirationAspiration of foreign bodies can obstructthe airway at the pharynx, larynx or bron-chial level. Foreign bodies are more likely toenter the right lung due to the anatomy ofthe mainstem bronchi.InfectionsCroup (laryngotracheobronchitis) is an in-fection of the lower respiratory tract whichcan lead to airway swelling, edema and ob-struction. The etiology is typically viral, al-though it can be caused by mycoplasma.Treatment is with cool mist oxygen and ra-cemic epinephrine.Epiglottitis is a medical emergency causedby an infection of the epiglottis. Haemophi-lus influenza type B is the most common eti-ology. Inflammation of the epiglottis can leadto complete airway obstruction. Epiglottitisis rare in the U.S. due to universal Haemo-philus vaccination (HiB) in infancy.

Obstructive lung diseaseAsthma attacks are characterized by bron-choconstriction and increased production ofsecretions in the airways. Narrowed airwaysand the increased work of breathing can tirethe respiratory muscles leading to respira-tory failure. Note that muscle fatigue,muscles and motion, is ultimately the causeof respiratory acidosis, but obstruction of theairway is the inciting event. (See page 416.)Chronic bronchitis is characterized by ob-struction of airflow from increased mucussecretion and airway destruction. Expirationis more difficult than inspiration which leadsto air trapping and hyperinflation. (See page422.)Emphysema is characterized by the loss ofelastic tissue in the lung. Without this sup-portive framework to maintain airway ten-sion, the distal airways collapse. (See page422.)SeizuresGrand mal seizures typically cause occlu-sion of the upper airway which can result inhypoxia and hypercarbia.Smoke inhalationSmoke inhalation can increase the mor-tality for burns by ten-fold. Burning poly-mers (e.g., carpets, insulation) release alde-hydes such as acrolein which damage theairway. Injury to the large airways can causeswelling and occlusion; injury to the alveolican cause pulmonary edema.

416


Clinical correlation: Acute asthma exacerbations can occurin two stages.

Asthma is a disorder characterized by reversible attacks of airwayobstruction. During an acute asthma exacerbation, there are two typesof obstruction: bronchoconstriction, which narrows the airways andmucus plugging (secondary to inflammation), which occludes the air-ways.

An acute asthma exacerbation can be described in two stages. In thefirst stage, bronchoconstriction and mucus plugging increase the workof breathing, and oxygenation is difficult to maintain. To maintain oxy-genation, ventilation increases. Increased ventilation lowers the PCO2causing respiratory alkalosis.

The second stage, if a patient does not improve, occurs when themuscles of respiration fatigue. The combination of airway obstructionand fatigue results in inadequate ventilation, CO2 retention and respi-ratory acidosis.

A normal or increased PCO2 in the face of an asthma exacerbation isalways a bad sign which can herald complete respiratory collapse andthe need for mechanical ventilation.

Respiratory alkalosisIncreased respiratory effortcauses an increase in ventila-tion. PCO2 is low and PO2 isnormal.

Note that respiratory failure from asthma is ultimately due to a failure of step two inrespiration: muscles and motion. Although respiratory failure is due to respiratory musclefatigue, the primary inciting event is obstruction of the airways, a defect in step threeof respiration: free flow.

Respiratory acidosisFatigue results in decreasedventilation. PCO2 is high andPO2 is low.

CCC

CCCCCCCCC

417


Gas exchange!The fourth step of respiration is the exchange ofgasses in the alveoli.

Gas exchange occurs exclusively in the alveoli which are specialized lungtissues surrounded by pulmonary capillaries. Normally, oxygen diffuses fromthe alveoli into the capillaries and carbon dioxide diffuses from the capillariesinto the alveoli. There are three types of defects at the alveolar level whichinterfere with gas exchange.

Diffusion defect: air and blood both reach the alveoli, but de-fects in the alveolar membrane prevent efficient gas exchange.Ventilation defect: blood reaches the alveoli, but air does not.Perfusion defect: air reaches the alveoli, but blood does not.

Ventilation defectBlood reaches the alveoli, butair does not.

Diffusion defectAir and blood reach the alveolibut defective membranes pre-vent gas exchange.

Perfusion defectAir reaches the alveoli, butblood does not.

O2

O2 O2CO2

CO2 CO2

CO2

CO2 CO2

CO2 CO2

CO2

O2

Gas exchange occurs exclusively in the _________.There are three types of defects which prevent gas exchange inthe alveoli: perfusion, ventilation and ___________.A ___________ defect is characterized by adequate perfusion andinadequate ventilation.

alveoli

diffusionventilation

418


The A-a gradient is a useful tool for detecting abnormal gas exchange. TheA-a gradient is the difference between Alveolar oxygen content and arterialoxygen content. The calculation is explained on the next page.

The A-a gradient can be thought of as the difference between how muchoxygen can enter the blood (the alveolar oxygen content) and how much oxy-gen does enter the blood (the partial pressure of arterial oxygen measured onthe ABG). If gas exchange between the alveoli and pulmonary capillaries wereperfect (all of the alveolar oxygen crossed into the blood), the A-a gradientwould be zero. However, due to normal physiologic impediments to gas ex-change, the A-a gradient is normally about 10 in a healthy young adult. Anincreased A-a gradient indicates that an abnormality in gas exchange has inter-fered with the transfer of oxygen into blood.

The A-a gradient can be used clinically to identify disorders of gas exchange.If impaired gas exchange is the sole or a contributing cause of respiratory aci-dosis, then the A-a gradient is increased. If, however, respiratory acidosis isdue to a ventilation defect (one or more the first three steps of respiration), thenthe A-a gradient is normal.

If respiratory acidosis is secondary to a defect in ventilation, thenthe A-a gradient is _________.

aaanormal

CO2 CO2

CO2 O2

O2O2

O2

O2

O2Sensing and signalling defect

Free flow defect

Gas exchange defect

A-a gradient is normal A-a gradient is high

+

Gas exchange!The A-a gradient identifies abnormal gas exchange.

Muscles and motion defect

419


Partial pressure of oxygen Resp. quotient–

Gas exchange!Calculation of the A-a gradient is important inevaluating disorders of respiration.

Alveolar O2 Arterial O2

PO2(1.25 × PCO2)%FiO2barometricpressure

partial pres.of H2O vapor– ) ×( – –

(760 mmHg – 47 mmHg) (1.25 × 40 mmHg) 90 mmHg

The A-a gradient is the alveolar oxygen content minus the arterial oxygencontent. The calculation is shown above. The example above calculates thenormal A-a gradient for someone at sea level, breathing room air.

The alveolar oxygen content is dependent on many factors: the barometricpressure, partial pressure of water vapor, percentage of oxygen in inspiredair (FiO2) and the partial pressure of CO2 in the alveoli. Barometric pres-sure is dependent on elevation. Water vapor pressure is a constant. Roomair contains 21% oxygen.

The presence of CO2 in the alveoli reduces the alveolar oxygen content.The effect of CO2 is factored in by calculating the respiratory quotient andsubtracting it from the partial pressure of oxygen. The PCO2 needed to de-termine the respiratory quotient is obtained from the ABG.

The arterial oxygen is the measured value obtained from the ABG.

The A-a gradient is the alveolar _______ content minus the________ oxygen content.Alveolar oxygen is calculated from the FiO2, PCO2 and barometricpressure, while the arterial oxygen is measured by the ____.

oxygenarterial

ABG

Barometric pressure at sea level ... 760 mmHgNormal water vapor pressure ................ 47 mmHgRoom air FiO2 ........................................................................ 21%Normal PCO2 ........................................................... 40 mmHgNormal PO2 ................................................................ 90 mmHgNormal Aa-gradient ........................................... 10 mmHg

–

A-a gradient–

–

=

× 0.21 = 10 mmHg

As people age, the normal A-a gradient increases. The normal A-a gradient is estimated bythe following formula: (Age÷4) + 4.Therefore, an 80 year old will have a normal A-a gradient of (80÷4) + 4 = 20 + 4 or 24;

a 20 year old will have a normal A-a gradient of (20÷4) + 4 = 5 + 4 or 9.

420


Diffusion defectAlpha1-antitrypsin deficiency is a geneticdisease which causes emphysema. Alpha1-antitrypsin is an enzyme which decreases theactivity of the proteolytic enzyme trypsin. Italso decreases the activity of elastase andother proteases which break down the con-nective tissues of the lung. Lack of this en-zyme allows tissue destruction to continueunchecked.Because the disease is genetically recessive,two defective alleles must be present for thedisease to occur. In patients who are homozy-gotes for a defective allele, emphysema oc-curs in the third or fourth decade of life.Emphysema is the destruction of the bron-chioles and alveoli, resulting in large pock-ets of air with a relative lack of alveolarwalls. Since gas exchange occurs only acrossthe alveolar wall, emphysema directly pre-vents the exchange of carbon dioxide andoxygen. The most common cause of emphy-sema is smoking.Interstitial lung diseases are a heteroge-neous group of disorders characterized byacute or chronic infiltration of the alveolarwalls with cells, fluid and fibrotic tissue.There are numerous causes of interstitiallung disease including:

• amiodarone pulmonary toxicity• amyloidosis• ankylosing spondylitis• bronchiolitis obliterans organizing

pneumonia (BOOP)• idiopathic pulmonary fibrosis• organic and synthetic dust exposure

(e.g., asbestos)• radiation therapy• rheumatoid arthritis• sarcoidosis• Wegener’s granulomatosis

Ventilation defectAdult respiratory distress syndrome(ARDS) is a severe pulmonary disease char-acterized by influx of neutrophils, red bloodcells and proteinaceous fluid into the alveoli.The influx of fluid and cells prevents gasexchange across the alveolar walls. ARDS isusually the result of serious illness (e.g., sep-sis, pancreatitis, trauma, aspiration of gas-tric contents and burns).Atelectasis is the absence of air in the al-veoli which causes segmental collapse of lungtissue.Pulmonary edema is the filling of the al-veoli with fluid. The most common etiologyof pulmonary edema is congestive heart fail-ure. (See page 59.)Pneumonia is a generic term for infectionand inflammation of the lung parenchyma.The alveolar spaces fill with blood cells andfibrin (pus). Because the alveoli are filledwith the products of inflammation, gas ex-change is impaired.Perfusion defectPulmonary embolism is a blood clot whichbreaks away from a larger clot and flowsthrough the venous system until it lodges inthe pulmonary arteries of the lung. It pre-vents blood flow distal to the clot, resultingin poor gas exchange. Usually, the source ofthe embolism is a thrombus in the iliofemo-ral deep veins. Common presenting symp-toms and signs include dyspnea, tachycar-dia, pleuritic chest pain (pain increases withbreathing) and cough.

Gas exchange!Many disorders interfere with gas exchange.The disorders of gas exchange are usually characterized by hypoxemia, hy-

perventilation and respiratory alkalosis. Only when these disorders are severeand/or long-standing does carbon dioxide retention and respiratory acidosisoccur.

421


COPD is associated with air trapping and hy-perinflated lungs due to the destruction ofseptal walls and connective tissue. This de-struction causes the airways to lose tonewhich interferes with ventilation. During ex-halation, the airways collapse, trapping airin the lungs. The air trapping leads to hyper-inflated lungs at the end of expiration so thatexpansion of the chest during inspiration islimited.

Clinical correlation: COPD causes abnormalities in all four stepsof respiration.

Chronic respiratory acidosis alters the res-piratory control center so that it becomes lesssensitive to changes in carbon dioxide. Pa-tients with chronic hypercarbia are depen-dent on changes in oxygenation to drive res-piration.

+

COPD interferes with the free flow of air bya number of different mechanisms.Emphysema destroys the elasticity thatholds the bronchioles open, especially dur-ing expiration. Without the septal walls, thebronchioles collapse and obstruct the air-way.Chronic bronchitis is characterized byincreased mucous production which ob-structs and narrows the airway.The destruction of the alveolar septa asso-ciated with COPD interferes with gas ex-change. The loss of surface area reducesthe area available for the exchange of CO2and O2.Interference with gas exchange increasesthe A-a gradient.

CO2 CO2

CO2 O2

O2O2

O2

O2

O2

sensing and signaling

muscles and motion

free flow

gas exchange

Respiratory acidosis is commonly due to a defect in more than onestep in the process of respiration. COPD is an excellent example of this,as there are defects in every step of respiration.

422


EmphysemaDilation and air trapping in the distalalveoli with destruction of alveoli sep-tal tissue

Pink puffers

These patients are dyspneic andbreathe heavily (puffers) in order tomaintain adequate ventilation andoxygenation (pink).

Late in the disease

Early in the disease

Late in the disease

Less common, but more severe

Definition

Mnemonic

What themnemonic

means

Cough

Dyspnea

Hypoxia

Infections

Clinical correlation: COPD is typically a combination of twodisease processes.

Chronic obstructive pulmonary disease (COPD) is a common cause ofrespiratory acidosis. Patients with COPD have difficulty completely exhal-ing which produces an obstructive pattern on pulmonary function tests (FEV1, FVC and FEV1 ⁄FVC). COPD is the most common cause of chronicrespiratory acidosis. The two types of COPD are chronic bronchitis andemphysema; usually, patients have a combination of both disorders, al-though one of the two typically predominates.

Emphysema is defined histologically as dilation of the alveolar air sacswith destruction of alveolar septa. Chronic bronchitis is defined clini-cally as an increase in bronchial mucus production sufficient to cause acough for at least three months per year for at least two consecutive years.

Smoking is the predominant risk factor for COCOPDcauses hypertrophy of goblet cells, increasing mucus production. Ciga-

rette smoke also inhibits ciliary action which prevents clearing excess mu-cus and predisposes to chronic bronchitis. Cigarette smoke recruits in-flammatory cells which release proteolytic enzymes that break down al-veolar tissue resulting in emphysema.

Chronic bronchitisExcessive sputum production forgreater than 3 months of the year forat least 2 consecutive years

Blue bloaters

These patients do not experiencedyspnea until end-stage disease butare hypoxic (blue). These patients areedematous due to right-sided heartfailure (bloaters).

Early in the disease

Late in the disease

Compensation early in the disease byincreasing hematocrit

Common, but less severe

423


Examination of the Henderson-Hasselbalch formula reveals that normal-ization of the HCO3

–/CO2 ratio in respiratory acidosis requires an elevationof plasma HCO3

–. Increased plasma HCO3– in respiratory acidosis occurs

through buffering and renal excretion of hydrogen. The buffering responseoccurs within hours, but produces only a minimal effect. Renal compensa-tion produces a large effect, but is not complete for 3-5 days.

Because of the time necessary for renal compensation to occur, two formsof respiratory acidosis are recognized: acute and chronic. Acute respiratoryacidosis is present before renal compensation is complete, and chronic res-piratory acidosis is present after renal compensation is complete.

In respiratory acidosis the PCO2 is ________ (increased/decreased).The compensation for respiratory acidosis is an__________ (increase/decrease) in HCO3

–.Acute respiratory acidosis exists before ________ compensation iscomplete.

increased

increaserenal

Acuterespiratory acidosisbefore renal compensation

Chronicrespiratory acidosisafter renal compensation

3-5days

pH HCO3–

CO2

CCC

CC

Compensation!The compensation for respiratory acidosis is anincrease in bicarbonate.

pH HCO3–

CO2

424


Compensation!Acute!Buffering by bicarbonate in respiratoryacidosis is ineffective.

Although buffering is the initial compensatory response in acute respiratoryacidosis, the effect is minimal because bicarbonate, the primary acid buffer, isineffective. Normally in acidemia, excess hydrogen ion combines with bicar-bonate to produce carbonic acid which breaks down into water and carbondioxide. The excess carbon dioxide produced by this reaction is then eliminatedby the lungs via respiration. As carbon dioxide is eliminated, the reaction con-tinues forward and more acid can be buffered.

In respiratory acidosis, the primary defect is ineffective respiration which re-sults in the retention of carbon dioxide. Thus, bicarbonate cannot serve as abuffer because the carbon dioxide produced by the buffering reaction cannotbe eliminated. Only non-bicarbonate buffers such as protein, phosphate andhemoglobin can effectively absorb excess hydrogen ions.

Buffering in respiratory acidosis

HCO3– is an ineffective buffer in res-

piratory acidosis because CO2 can-not be eliminated.

Intracellular buffers (phosphate, hemoglobin) andbone are the primary buffers in respiratory acido-sis.

PO4–

Normal buffering

CHCO3 H+HCO3 H+

Normally in acidemia, bicarbon-ate combines with excess hy-drogen ion to form...

carbonic acidwhich breaksdown into...

water and CO2. ExcessCO2 is eliminated bythe lungs.

CCC

CC

The major hydrogen ion sponge in the body is ___________.In respiratory acidosis, _________ is an ineffective buffer becausethe CO2 produced in the buffering reaction cannot be eliminated.

bicarbonatebicarbonate

425


Due to relatively ineffective buffering and the lack of a renal response, acuterespiratory acidosis is characterized by only a modest elevation in HCO3

–. Asrepresented in the graph above, the concentration of HCO3

– changes very littlefor a given elevation of CO2. (Note how flat the acute respiratory acidosiszone is on the graph.)

Although small, the non-bicarbonate buffers do effect a relatively consistentchange in the concentration of HCO3

– for a rise in CO2. The change in bicarbon-ate relative to the change in PCO2 is 1:10. For every 10 mmHg rise in PCO2, theHCO3

– rises by 1 mEq/L. For example, if the PCO2 increases from 40 mmHg to60 mmHg, then the HCO3

– should increase from 24 mEq/L to 26 mEq/L.

Compensation!Acute!The bicarbonate increase in acute res-piratory acidosis is small.

The small increase in bicarbonate concentration in respiratoryacidosis is secondary to the effect of non-bicarbonate _________.In acute respiratory acidosis, the bicarbonate concentration in-creases by ___ mEq/L for every 10 mmHg elevation in PCO2.

AAAbuffers

one

HCO3– : PCO2 .................................................... 1 : 10

( )expected HCO3– = 24 + PCO2 – 40

10

ACUTE RESPIRATORY ACIDOSIS

35

38363432302826242220181614

40 45 50 55 60 65 70 75

normal

chronic respiratory acidosis

acute respiratory acidosis

Bic

arbo

nate

(mEq

/L)

PCO2 (mmHg)

426


Compensation!Chronic!Respiratory acidosis is referred to aschronic when renal compensation is complete.

Respiratory acidosis is defined as chronic only after renal compensationis complete. The renal compensation for respiratory acidosis involves en-hanced excretion of hydrogen.

In respiratory acidosis, the bicarbonate buffer equation is shifted to theleft. Carbon dioxide and water combine to form carbonic acid which breaksdown into hydrogen ion and bicarbonate. The excess hydrogen ion is thenexcreted by the kidney. As hydrogen ion is excreted by the kidney, new bi-carbonate is added to the plasma. The increase in plasma bicarbonate bal-ances the increase in PCO2, lowering the pH toward normal.

3-5days

pH HCO3–

CO2

pHHCO3

–

CO2

HCO3 H+

H+ H+

NEW!HCO3

NEW!HCO3

NEW!HCO3 H+

H+

CCCCC

CC

Renal compensation in respiratory ________is the increased ex-cretion of hydrogen ion which results in the production of____________.Renal compensation in respiratory acidosis takes ___ to ___days to complete.

acidosisbicarbonate

3;5

427


123

4

Na+

H+

Na+

Cl–

intercalated cell

OH

CO2

ATP

AMP

H+

NEW!

HCO3

The creation of new bicarbonate and excretion of hydrogen ion occurs inthe intercalated cells of the collecting ducts.

Water (H2O) in the tubular cells breaks down into H+ and OH–. Hydrogenion is secreted into the tubular lumen by the H+- ATPase pump. To maintainelectroneutrality, sodium ions flow down their concentration gradient intothe cell. The increased resorption of sodium leaves fewer sodium ions avail-able to be resorbed with chloride. Chloride excretion in the urine is increasedwith increased hydrogen excretion.

In the tubular cell, OH– combines with CO2 to form bicarbonate whichenters the plasma. The formation of bicarbonate from OH– and CO2 is cata-lyzed by the enzyme carbonic anhydrase.

The renal excretion of hydrogen results in loss of chloride and formationof additional bicarbonate for the plasma. Plasma chloride is decreasedand plasma bicarbonate is increased.

Clinical correlation: Renal excretion of hydrogen increasesurinary chloride loss.

When H+ is secreted, Na+ isresorbed to maintain elec-troneutrality.

Normally, Cl– and Na+ re-sorption occur together. Be-cause Na+ is resorbed inexchange for H+, less Na+ isavailable for Cl– resorption.

Acidemia increases the se-cretion of H+.

Increased urinary chloridelosses result in a low plasmachloride.

water (H2O)

428


Compensation!Chronic!Renal compensation for chronic res-piratory acidosis causes a more dramatic increase in bicarbonatethan buffering alone.

Renal compensation for respiratory acidosis produces a largerincrease in __________ concentration for a given change in PCO2than buffering alone.In acute respiratory acidosis, for every 10 mmHg _______ in car-bon dioxide the bicarbonate increases by _______ .In chronic respiratory acidosis, for every 10 mmHg _______ incarbon dioxide the bicarbonate increases by _______ .

aaabicarbonate

increaseone

increasethree

Chronic respiratory acidosis is characterized by a more significant com-pensatory rise in plasma HCO3

– than occurs in acute respiratory acidosis. Asrepresented in the graph above, the change in plasma HCO3

– for a givenchange in PCO2 is much greater in chronic than in acute respiratory acido-sis. In chronic respiratory acidosis, the change in bicarbonate relative to thechange in PCO2 is 3:10. For every 10 mmHg rise in PCO2, the HCO3

– rises by3 mEq/L. For example, if the PCO2 increases to 60 mmHg from 40 mmHg,then the HCO3

– should increase from 24 mEq/L to 30 mEq/L.

Chronic respiratory acidosis

CHRONIC RESPIRATORY ACIDOSIS

HCO3– : PCO2 ...................................................... 3 : 10

expected HCO3– = 24 + 3 × 40 – PCO2( )10

35

38363432302826242220181614

40 45 50 55 60 65 70 75

normal

chronic respiratory acidosis

acute respiratory acidosis

Bic

arbo

nate

(mEq

/L)

PCO2 (mmHg)

429


Clinical correlation: Identifying the presence of other acid-base disorders requires calculation of the expected bicarbon-ate concentration.

When respiratory acidosis is identified, the first step in the evalua-tion is to assess compensation and determine if another acid-base dis-order is present. By using the formulas for the predicted bicarbonate,the presence of an additional acid-base disorder can be determined.

If the bicarbonate does not match the level predicted for either acute orchronic respiratory acidosis, then a second acid-base disorder is present.Metabolic acidosis is present when the bicarbonate is below predicted andmetabolic alkalosis is present when the bicarbonate is above predicted.

If the bicarbonate is between the predicted amount for acute andchronic respiratory alkalosis, then four combinations of acid-base dis-orders could explain this result:

• chronic respiratory acidosis and metabolic acidosis or• acute respiratory acidosis and metabolic alkalosis or• acute-on-chronic respiratory acidosis or• acute respiratory acidosis becoming chronic

Common scenarios of respiratory acidosis with other acid-base disor-ders are discussed on the following page.

CCCCCCCCC

?

430


diuretic use

Respiratory acidosis and metabolic acidosis. Patients with thiscombination of acid-base disorders usually have profound acidemia andare very sick. This can be seen in a patient with pneumonia and sepsis.Pneumonia causes respiratory acidosis, and sepsis causes metabolic aci-dosis. Patients with cardiogenic shock can also have the combination ofrespiratory acidosis and metabolic acidosis. Heart failure causes pul-monary edema and respiratory acidosis while inadequate cardiac out-put causes metabolic acidosis from accumulation of lactic acid.

Respiratory acidosis and metabolic alkalosis. An example of thiscombination of acid-base disorders is the patient with COPD (respira-tory acidosis) taking diuretics (metabolic alkalosis). Diuretics are fre-quently prescribed to manage lower extremity edema in patients withadvanced COPD and right-sided heart failure.Acute-on-chronic respiratory acidosis. Patients with COPD com-monly develop other causes of respiratory acidosis. These patients of-ten present with a new, acute cause of respiratory acidosis in additionto their base-line chronic respiratory acidosis. This is known as acute-on-chronic respiratory acidosis and is commonly caused by pneumonia.

Clinical correlation: Other acid-base disorders commonlyoccur with respiratory acidosis.

cardiogenic shock

R.I.P.

respiratory failure frompneumonia

respiratory acidosis and metabolic acidosis

COPD COPD

respiratory acidosis and metabolic alkalosis acute-on-chronic respiratory acidosis

pneumonia

sepsis pulmonary edema

or

431


Symptoms and signs!Neurologic symptoms and signs predom-inate in respiratory acidosis.

The symptoms and signs of respiratory acidosis are primarily neurologicdue to the effect of cerebral acidosis. Cerebral acidosis stimulates vasodila-tion which increases cerebral blood flow and intracranial pressure. Initially,increased cerebral blood flow may cause headaches. As cerebral acidosisworsens, restlessness and stupor may develop. Carbon dioxide narcosis isthe development of somnolence and depressed consciousness from risingCO2 levels.

Hypoxia is always present in respiratory acidosis. Hypoxia can cause cy-anosis and contribute to altered mental status.

hypoxia

Oxygen

ZZZ

carbon dioxidenarcosis

increased cerebralflood flow

stupor, coma

CO2 narcosis is the development of __________ from rising CO2levels.Respiratory acidosis ___________ (decreases/increases) cerebralblood flow which may cause headaches.C3PO! Shut down all of the garbage mashers on the___________ level!

somnolence

increases

detension

OUCH!

headaches

432


The clinical picture associated with chronic respiratory acidosis is domi-nated by the signs and symptoms of chronic lung disease. By far, the mostcommon cause of chronic lung disease is COPD. The symptoms and signs ofthis disease are discussed below.

Due to the underlying pulmonary disease, shortness of breath and coughare common complaints. Chronic hypoxemia may affect cognitive abilitiesand cause cyanosis. To compensate for chronically low oxygen, RBC produc-tion may increase resulting in an increased hematocrit (known as poly-cythemia). Chronic CO2 retention can cause somnolence and headaches.

As the disease progresses, the loss of pulmonary blood vessels results inpulmonary hypertension and right-sided heart failure (cor pulmonale). Right-sided heart failure can cause lower extremity edema and chest pain.

Physical exam findings in a patient with COPD may include a barrel-shaped chest, prolonged expiration and wheezing. All of these findings arecaused by air trapping due to obstruction of air flow during exhalation.

Symptoms and signs!The symptoms and signs in COPD aremainly due to the underlying lung disease.

OUCH!

headaches confusion polycythemia

barrel-shaped chest right-sided heart failure

Increased hematocrit, also known as _____________, can occur inCOPD in order to compensate for chronic __________.In COPD, obstruction of the airways interferes with exhalation causing airtrapping, prolonged exhalation, an enlarged chest cavity (_________-shaped) and wheezing.

polycythemiahypoxia

barrel

433


Diagnosis!Identifying the underlying cause of respiratory acidosis re-quires review of the patient data base.

Establishing the cause of respiratory acidosis can be difficult because awide range of respiratory diseases exist. Some of the important componentsof the history, physical exam and lab tests are discussed below.

History. The history is important to establish if an underlying lung dis-ease is already present (e.g., asthma, COPD). Patients with COPD com-monly have exacerbations from infections which cause acute-on-chronic res-piratory acidosis.

Physical exam. An assessment for breathlessness should be made (e.g.,can the patient speak in full sentences) and whether accessory muscles ofrespiration are being used. A careful lung exam should be done, assessingfor crackles, dullness to percussion, egophony, tactile fremitus and wheezes.Look at the fingers for clubbing, a sign of chronic hypoxia.

Labs and other tests. The A-a gradient is a useful tool in the evaluation ofrespiratory acidosis. The A-a gradient is normal in disorders of ventilation (e.g.,obesity hypoventilation, narcotic use); it is increased in disorders of impairedgas exchange (e.g., pneumonia, pulmonary embolism). Because more than onestep in the process of respiration may be affected, an increased A-a gradientdoes not exclude a concurrent impairment in ventilation.

A CXR is helpful to identify the presence of infiltrates, pulmonary edemaor pleural effusion.

HistoryasthmaCOPDCHFfevercoughchest painillicit drug usetrauma

Physical examincreased respiratory rateincreased breathlessnesspresence of obesityinability to complete sentencesuse of accessory musclesclubbingcracklesegophonydullness to percussionwheezingtactile fremitus

Labs and other testsChest X-ray (CXR)ABGA-a gradientpotassiumphosphatemagnesiumhematocrit

Well, it allbegan whenI was sittingon my frontporch mind-ing my ownb u s i n e s s ,and thesetwo guys......

A most useful tool in the evaluation of respiratory acidosis is the____ gradient.

aaaA-a

434


Diagnosis!Abnormal lab values in respiratory acidosis are foundprimarily on the chem-7 and arterial blood gas (ABG).

Respiratory acidosis is characterized by the following lab abnormalities:The ABG is characterized by a low pH with a high PCO2. Pulmonary dis-

ease severe enough to cause carbon dioxide retention also causes hypoxia;thus, the PO2 is low.

The chem-7 is characterized by an increased bicarbonate, representingcompensation by buffering (acute respiratory acidosis) and renal excretionof hydrogen ion (chronic respiratory acidosis). In chronic respiratory acido-sis, the bicarbonate can reach as high as 40 mEq/L.

Chloride may be slightly low due to increased renal loss. Renal loss ofchloride increases to maintain electroneutrality with hydrogen loss.

The Alveolar-arterial gradient may be normal or high, depending onwhether an impairment in gas exchange is present. Impaired gas exchangeincreases the A-a gradient.

pH / PCO2/ PO2Cl–

HCO3– glucoseK+

BUN

CrNa+

In respiratory acidosis, the bicarbonate is __________ (decreased/increased) and the chloride is __________ (decreased/increased).If gas exchange is impaired, the A-a gradient is typically__________ (normal/high).

increaseddecreased

high

435


The most important aspect in the treatment of respiratory acidosis is toidentify and treat the underlying cause.

Supplemental oxygen should be given to return oxygen levels to normal.Care must be used when using oxygen in patients with chronic carbon diox-ide retention. Other important measures include nebulizer treatments withalbuterol for asthma, antibiotics for pneumonia and diuretics for cardio-genic pulmonary edema. Steroids are used in a number of pulmonary dis-eases to reduce inflammation (e.g., asthma, BOOP).

If the pulmonary process causing respiratory acidosis cannot be reversedor is severe, endotracheal intubation and mechanical ventilation may berequired. Mechanical ventilation can be used to support ventilation whilereversible causes of lung injury are treated (e.g., antibiotics are given totreat pneumonia). The decision to institute mechanical ventilation is a clinicaldecision dependent on many factors (e.g., patient fatigue, reversibility ofillness, patient preference, etc.).

Treatment!In respiratory acidosis, treating the underlying disorderis important.

Treat the underlying disorder.

Mechanically ventilate, if necessary.

Oxygen

supplemental oxygen diuretics steroidsantibiotics

Methylprednisolone

Since respiratory acidosis is associated with hypoxia, one of themainstays of treatment is to give supplemental _________.Albuterol can be helpful in patients with ________.

aaaoxygenasthma

436


Respiratory acidosis can be due to a defect in one or more of the four stepsof respiration: sensing and signaling, muscles and motion, free flow and gasexchange. Ventilation, the delivery of air to the alveoli, occurs in the firstthree steps of respiration. Usually, respiratory acidosis is due to a combina-tion of defects.

CO2 CO2

CO2 O2

O2O2

O2

O2

O2

free flow gas exchangesensing and signaling muscles and motion

pH HCO3

–

CO2pH

HCO3–

CO2

pH HCO3

–

CO2pH

HCO3–

CO2

metabolic acidosis metabolic alkalosis respiratory acidosis respiratory alkalosis

Respiratory acidosis is one of the four primary acid-base disorders and ischaracterized by a PCO2 greater than 40 mmHg and pH below 7.4. Bufferingand renal compensation cause the bicarbonate to rise above 24 mEq/L.

Summary!Respiratory acidosis.

To compensate for the low pH of respiratory acidosis, plasma bicarbonateincreases to balance the increased carbon dioxide. Bicarbonate increasesthrough intracellular buffering (acute respiratory acidosis) and renal reten-tion with production of bicarbonate (chronic).

Acute respiratory acidosis exists prior to renal compensation; chronic res-piratory acidosis exists after renal compensation is complete. Compensa-tion is assessed by calculating the expected bicarbonate. If the measuredbicarbonate does not match the values predicted by the formulas, then asecond acid-base disorder is present.

CHRONIC RESPIRATORY ACIDOSIS

HCO3– : PCO2 ...................................................... 3 : 10

expected HCO3– = 24 + 3 × 40 – PCO2( )10

HCO3– : PCO2 .................................................... 1 : 10


10

ACUTE RESPIRATORY ACIDOSIS

437


A useful test in the evaluation of respiratory acidosis is the A-a gradient.The A-a gradient is the difference between the amount of oxygen in theAlveoli and the amount of oxygen in the arterial blood. The normal A-agradient increases with age. In young healthy adults it is about 10.

Summary!Respiratory acidosis.

A-a gradient

normal Aa-gradient = (age + 4)4

The symptoms and signs of respiratory acidosis are different, dependingon whether it is acute or chronic. The symptoms and signs of acute respira-tory acidosis are due to hypoxia, hypercarbia and cerebral acidosis. Thepresentation can range from tachypnea and headaches to CO2 narcosis withstupor or even coma.

Since chronic respiratory acidosis is associated with long-standing pul-monary disease, the symptoms and signs of chronic respiratory acidosis aredominated by the symptoms and signs of chronic pulmonary disease (COPD).

Lab abnormalities associated with respiratory acidosis include decreasedpH, increased PCO2, decreased PO2, decreased Cl– and increased HCO3

–.The treatment of respiratory acidosis focuses on identifying and treating

the underlying disorder.

pH / PCO2/ PO2Cl–

HCO3– glucoseK+

BUNNa+

%O2barometricpressure

partial pressureof H2O– )×[( ]– –(1.25 × PCO2) PO2

Cr

438


Step 3. !!!!!History, physical, labs and other tests.

Normal A-a gradient (Ventilation defect)

Summary!Clinical review.Step 1. Recognize respiratory acidosis.

Step 2. !!!!!Compensation, determine acute versus chronic and eval uate for the presence of other acid-base disorders.

HCO3–pH / PCO2/ PO2

Sensing and signalingSensing defects

apnea of prematuritybrain stem injurycentral sleep apnea

Drugsnarcoticsalcoholbenzodiazepinesoxygen therapy in patients

with chronic CO2 retentionObesity hypoventilationPrimary hypoventilationSignaling defects

amyotrophic lateral sclerosisdiaphragmatic paralysisGuillain-Barré syndromepost-polio syndromespinal cord injury

Step 4. Calculate the A-a gradient.

HistoryasthmaCOPDCHFfevercoughchest painillicit drug usetrauma

Physical examincreased respiratory rateincreased breathlessnesspresence of obesityinability to complete sentencesclubbingcracklesegophonydullness to percussionwheezingtactile fremitus

Labs and other testsChest X-rayABGpotassiumphosphatemagnesiumhematocrit

Muscles and motionAnatomic/Trauma

flail chestkyphoscoliosispneumothorax

Drugsaminoglycosidesuccinyl cholinevecuronium

Electrolyteshypokalemiahypophosphatemiahypermagnesemia

Genetic disordersacid maltase deficiencymuscular dystrophyperiodic paralysis

Myasthenia gravis

Free flowAnatomic

laryngomalaciatracheomalacia

AspirationInfections

croupepiglottitis

Obstructive diseaseasthmaCOPD

chronic bronchitisemphysema

SeizuresSmoke inhalation

Gas exchangeDiffusion defect

-antitrypsin deficiencyemphysemainterstitial lung disease

ankylosing spondylitisamiodarone toxicityamyloidosisBOOPdust exposuresidiopathic pulmonary

fibrosisrheumatoid arthritisradiation therapysarcoidosisWegener’s

granulomatosisVentilation defect

ARDSatelectasispulmonary edemapneumonia

Perfusion defectspulmonary embolism

High A-a gradient*

* A high A-a gradient does not exclude a concurrent ventilation defect.

HCO3– : PCO2 ...................................................... 3 : 10

expected HCO3– = 24 + 3 × 40 – PCO2( )10

HCO3– : PCO2 .................................................... 1 : 10


10

Acute Chronic

15 respiratory acidosis

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