RESPIRATORY FAILURERESPIRATORY FAILURE

MiklMiklós Molnárós Molnár

Semmelweis University Institute of Semmelweis University Institute of PathophysiologyPathophysiology

20052005

RespirationRespiration

Function of the respiratory system is to supply the Function of the respiratory system is to supply the body with oxygen for aerobic metabolism and to body with oxygen for aerobic metabolism and to remove its major metabolic waste product-carbon remove its major metabolic waste product-carbon dioxide dioxide (0.2-4 L/(0.2-4 L/minmin)). .

Does it by 3 Distinct Mechanisms: Does it by 3 Distinct Mechanisms: Ventilation: Ventilation: Delivery of ambient air to the alveoliDelivery of ambient air to the alveoli Diffusion: Diffusion: Movement of oxygen and carbon dioxide across the Movement of oxygen and carbon dioxide across the

alveolar air sac and capillary wallalveolar air sac and capillary wall Circulation: Circulation: Method by which oxygen is carried from site of gas Method by which oxygen is carried from site of gas

exchange to the cells where active metabolism occursexchange to the cells where active metabolism occurs

RespirationIs dependent on vital links of

various anatomic subcomponents

Central Nervous System

Thorax and Pleura

Neuromuscular System

Spinal Cord

Upper Airways

Cardiovascular Systemand Blood

Lower Airways and Alveoli

Seven anatomic subcomponents whose functions are vital to the maintenance Seven anatomic subcomponents whose functions are vital to the maintenance of normal respiration. Interruption in the function of any of the links has of normal respiration. Interruption in the function of any of the links has serious implications for the functioning of the system as a whole. serious implications for the functioning of the system as a whole. (adapted from Bone RC: Acute Respiratory Failure: Definition and Overview. In Bone R, ed: Pulmonary and (adapted from Bone RC: Acute Respiratory Failure: Definition and Overview. In Bone R, ed: Pulmonary and Critical Care Medicine. St. Louis: Mosby, 1997).Critical Care Medicine. St. Louis: Mosby, 1997).

Control of BreathingControl of Breathing

• Central chemoreceptorsCentral chemoreceptors• Respiratory centerRespiratory center – – medulla oblongatamedulla oblongata

•pH (pH (behind the blood-brain barrierbehind the blood-brain barrier))

• Peripheral chemoreceptors – Peripheral chemoreceptors – carotid carotid bodies bodies (carotis,(carotis, arch of aorta arch of aorta))

•pHpH/pCO/pCO22, pO, pO22

• mechanoreceptormechanoreceptorss ((lunglung, , chest wallchest wall))•mechanimechanicalcal strechstrech, , chemical irritationchemical irritation, ,

•J-receptorJ-receptorss

((juxtacapillarjuxtacapillar localization localization blood volume,blood volume, interstitial edemainterstitial edema))

Ventilatory Responses to Physiologic Ventilatory Responses to Physiologic StimuliStimuli

HypercapniaHypercapnia Gradual increase of frequencyGradual increase of frequency ((pCOpCO22=40-70 mmHg, linear=40-70 mmHg, linear -3 -3

l/min/mmHg)l/min/mmHg)

HypoxiaHypoxia normanormal PaOl PaO22=90 mmHg no effect=90 mmHg no effect, PaO, PaO22==550-55 mmHg yes0-55 mmHg yes

MetaboliMetabolicc acid acidosisosis activityactivity of the of the periperipheralpheral chemoreceptor chemoreceptor ↑↑

hyperventilation hyperventilation pCOpCO22↓↓,, later in thelater in the CNSCNS - 24-48 h.- 24-48 h.

Metabolic alkalosisMetabolic alkalosis activityactivity of the of the periperipheralpheral chemoreceptor chemoreceptor ↓↓

hypoventilation hypoventilation pCOpCO22 ↑↑, , later in thelater in the CNSCNS - 24-48 h.- 24-48 h.

Abnormality of the Control of Abnormality of the Control of BreathingBreathing

Abnormal Breathing PatternAbnormal Breathing Pattern

normal

tachypnoe

Kussmaul

Time (min)6 min

Air

flo

w

Apnoe: breathing stops at expirationApneusia: breathing stops at inspiration

Abnormal Breathing PatternAbnormal Breathing Pattern

Time (min)1 min

Cheyne Stokes

Cluster Breathing(Biot Breathing)

Abnormal Breathing PatternAbnormal Breathing Pattern ((AtaxiAtaxic breathing)c breathing)

Voluntary

Self-controlled

Time (min)1 min

Abnormal Breathing PatternAbnormal Breathing Pattern SleepSleep apn apneaea

Hypoventillation and an irregular respiratory pattern during sleep with apnea last for 15-20 sec during the REM phase, usually.

Types:Central apnea(complete cessation of respiratory efforts - encephalitis, central

ischemia)

Obstructive apnea(intermittent upper airway obstruction, morbid obesity, redundant

pharingeal soft tissue, reduced upper airway size due to enlarged lymphatic tissue)

Mixed apnea(Central apnea followed by obstructive one)

Types of ApneaTypes of Apnea

Obstructive apnea

Central apnea

Mixed apnea

Vol

um

e

Airflow

Muscle activity

Airflow

Airflow

Muscle activity

Muscle activity

Coronal section of the head and neck showing the segment Coronal section of the head and neck showing the segment over which sleep related narrowing can occur (arrows).over which sleep related narrowing can occur (arrows).

Anatomy of obstructive sleep apnea.Anatomy of obstructive sleep apnea.

An obese young woman with the short, thick neck typically An obese young woman with the short, thick neck typically seen in patients with obstructive sleep apnea.seen in patients with obstructive sleep apnea.

PathophysiologyPathophysiology

Enlarged uvula resting on the base of the tongue (large arrow), along with Enlarged uvula resting on the base of the tongue (large arrow), along with hypertrophied tonsils (small arrows). The posterior pharyngeal erythema hypertrophied tonsils (small arrows). The posterior pharyngeal erythema may be secondary to repeated trauma from snoring or gastroesophageal may be secondary to repeated trauma from snoring or gastroesophageal refluxreflux

PathophysiologyPathophysiology

Elongated soft palate (arrows). In this patient, an increased anteroposterior Elongated soft palate (arrows). In this patient, an increased anteroposterior dimension caused the soft palate to rest on the base of the tongue in the relaxed dimension caused the soft palate to rest on the base of the tongue in the relaxed position.position.

PathophysiologyPathophysiology

Family members or Family members or partners complaint partners complaint that the patient has that the patient has loud snoring, loud snoring, nocturnal gasping or nocturnal gasping or choking.choking.

Clinical ManifestationClinical Manifestation

Sleep Apnea Syndrome is profoundly Sleep Apnea Syndrome is profoundly associated with hypertension independent of associated with hypertension independent of all relevant risk factors.all relevant risk factors.

Arrhythmias from mild to severe.Arrhythmias from mild to severe.

Motor vehicle accident : Six time increased Motor vehicle accident : Six time increased accident rate compared to the general accident rate compared to the general population.population.

Pathophysiologic ConsequencesPathophysiologic Consequences

TreatmentTreatment

Carbon Carbon dioxidedioxide

Water Water vapourvapour

OxygenOxygen

NitrogeNitrogenn

Stephen Hawking“A Brief History of Time”: 1988.

Someone told me that each equation I Someone told me that each equation I included in the book would halve the included in the book would halve the sales.sales.

Pulmonary Gas ExchangePulmonary Gas Exchange

AlveolAlveolaar Or O22 tensiontension ( (PAOPAO22==1100 00 mmmmHgHg))

Capillary blood leaving the alveolusCapillary blood leaving the alveolus ( (Pc’OPc’O22==1100 00 mmHgmmHg))

ArterialArterial O O22 tensiontension ( (PaOPaO22==990 mm0 mmHgHg))Ideal Alveolar Gas EquationIdeal Alveolar Gas EquationCalculation of PAO2 (considering ideal alveolus):

PAO2 = PIO2 – PACO2 x FIO2 +

(1-FIO2)

R

FIO2 : fraction of inspired O2 (0.21 in room air)R: gas exchange ration – metabolic respiratory quotient (CO2 production/O2 consumption=0.7-1.0, typical value of about 0.8)

PIO2: pO2 of the inspired gas(PIO2= 0.21x(760-47)=150 mmHg)

PAO2= PIO2 – PaCO2 x 1.25

Representation of the Decrease in Partial Representation of the Decrease in Partial Pressure of OPressure of O22 from Inspired Air from Inspired Air

Effectiveness of Oxygene Exchange in the Effectiveness of Oxygene Exchange in the LungLung

(Alveolo(Alveololar-lar-ArtArteeririalal ox oxygen differenceygen difference))

AlveoloAlveolo-arte-arteririalal gr gragientagientIdeIdealal situationsituation P(A P(A--a)a)=0=0Right-to-left shuntRight-to-left shunt (2 (2-4 %), ventilation-perfusion -4 %), ventilation-perfusion mismatchmismatch..

P (P (AA –– a) = 2.5 + 0.21 x a) = 2.5 + 0.21 x (age in years(age in years))

IfIf P P (A(A - a) > 20 mmHg on room air is abnormal - a) > 20 mmHg on room air is abnormal usually due to a parenchymal abnormality of the usually due to a parenchymal abnormality of the lunglung

Oxygen Content of Blood Oxygen Content of Blood (CaO(CaO22))

Bound to hemoglobinBound to hemoglobin ((major partmajor part))

Dissolved in plasmaDissolved in plasma ((small amountsmall amount))

CaOCaO22 = Hb x 1.39 x + 0.0031 x PaO= Hb x 1.39 x + 0.0031 x PaO22SaO2

100

Hb: hemoglobin (g/100ml)

1.39 : oxygen-carrying capacity of Hb (ml O2/g Hb)

SaO2: % of Hb that is bound to O2 = (oxygen saturation)0.0031: solubility coefficient for O2 in plasma (ml O2/100 ml/mmHg)

PaO2: partial pressure of O2 in arterial blood

Dissociation Curve of OxyhemoglobinDissociation Curve of Oxyhemoglobin

% o

f S

O2

PO2 (mmHg)

Physiologiclyimportant

Clinicallyimportant

Adaptations

Right shift:acidosisfever, 2,3-DPG

Left shift:alkalosiscold

Why the OWhy the O22 content is so important ? content is so important ?

+ =

Hb=15 g% Hb=15 g% Hb=15 g%

100 ml100 ml 200 ml

PaO2

30 mmHgPaO2

96 mmHgPaO2

? mmHg

??? (30 + 96 )/2 = 63 mmHg ???

!! WRONG !!

Right AnswerRight Answer%

of

SO

2

PO2 (mmHg)

O2 c

onte

nt

(ml/

100

ml b

lood

)

((12.4 12.4 + 19.8) / 2 = 16.1 ml O+ 19.8) / 2 = 16.1 ml O22/ 100 ml / 100 ml PaO PaO22= 42 mmHg= 42 mmHg

Respiratory FailureRespiratory Failure

Impaired gas exchange:Impaired gas exchange:

Hypoxia with or without hypercapnia

Can be subclassified into acute and Can be subclassified into acute and chronic presentationschronic presentations

Acute respiratory failure occurs when:Acute respiratory failure occurs when: pulmonary system is no longer able to meet the pulmonary system is no longer able to meet the

metabolic demands of the bodymetabolic demands of the body

Hypoxemic respiratory failure:Hypoxemic respiratory failure: PaOPaO22 60 mmHg when breathing room air 60 mmHg when breathing room air

Hypercapnic respiratory failure:Hypercapnic respiratory failure: PaCOPaCO2 2 50 Hgmm 50 Hgmm

Definitions of Respiratory FailureDefinitions of Respiratory Failure HypoxemiaHypoxemia

Classification of Respiratory FailureClassification of Respiratory Failure

Predominant Hypercapnica Hypoxemiab

Type

Acute

Chronic

Minutes to hours; nocompensatory changes

Minutes to hours; nocompensatory changes

Days to months; compensatory changespresentpH and HCO3

Days to months; compensatory changespresenthemoglobin

a PaCO2 > 50 mmHgb PaO2 < 60 mmHg

Respiratory FailureRespiratory Failure

Pump failure Lung failure

Nervous System

Thoraciccage

Resp.muscle

Nervous System

Thoraciccage

Resp.muscle

Hypercapnia Hypoxemia

Breakdown of respiratory failure into its two major components:Breakdown of respiratory failure into its two major components:

Pump failure and lung failure. The end results of pump failure is Pump failure and lung failure. The end results of pump failure is hypercapnia, and the end result of lung failure is hypoxemia.hypercapnia, and the end result of lung failure is hypoxemia.

Examples of Disease that Causes Respiratory Examples of Disease that Causes Respiratory FailureFailure

BRAINBRAIN Drug overdoseDrug overdose Cerebrovascular accidentCerebrovascular accident

SPINAL CORD, SPINAL CORD, NEUROMUSCULARNEUROMUSCULAR Myastenia Gravis SyndromeMyastenia Gravis Syndrome PolioPolio Guillian-Barre’Guillian-Barre’ Spinal cord trauma or tumorSpinal cord trauma or tumor

CHEST WALLCHEST WALL Flail ChestFlail Chest KyphoscoliosisKyphoscoliosis

UPPER AIRWAYSUPPER AIRWAYS Vocal cord paralysis or Vocal cord paralysis or

paradoxicalmotionparadoxicalmotion Tracheal stenosis, Tracheal stenosis,

laryngospasmlaryngospasm

LOWER AIRWAYS & LOWER AIRWAYS & LUNGSLUNGS AsthmaAsthma BronchitisBronchitis Chronic Obstructive Chronic Obstructive

Pulmonary DiseasePulmonary Disease Pulmonary EmbolismPulmonary Embolism Acute Respiratory DistressAcute Respiratory Distress PreumoniaPreumonia Alveolar HemorrhageAlveolar Hemorrhage

HEARTHEART Congestive Heart FailureCongestive Heart Failure Valvular AbnormalitiesValvular Abnormalities

Pump FailurePump Failure Lung FailureLung Failure

Pathophysiology of Respiratory Pathophysiology of Respiratory FailureFailure

Diffusion abnormalities:Diffusion abnormalities: disturbances in gas transfer disturbances in gas transfer across the alveolar capillary bed across the alveolar capillary bed

Ventilation-perfusion imbalance and intrapulmonary Ventilation-perfusion imbalance and intrapulmonary shunt:shunt: problems with matching pulmonary blood flow problems with matching pulmonary blood flow and ventilation and ventilation

Alveolar hypoventilationAlveolar hypoventilation: decreased alveolar ventilation: decreased alveolar ventilation

Pathophysiologic mechanisms for respiratory failure include:

Diffusion AbnormalitiesDiffusion Abnormalities

The process by which OThe process by which O22 and CO and CO22 move passively move passively across the alveolar capillary membrane that across the alveolar capillary membrane that depends upon its physical properties (thickness, depends upon its physical properties (thickness, area, and diffusibility) and solubility of the gas area, and diffusibility) and solubility of the gas

Problem mainly in chronic, less so in acute Problem mainly in chronic, less so in acute respiratory failurerespiratory failure

Problems with Matching Pulmonary Problems with Matching Pulmonary Blood Flow and VentilationBlood Flow and Ventilation

Ideally each alveolar capillary exchange unit would Ideally each alveolar capillary exchange unit would have perfect matching of ventilation and perfusion to have perfect matching of ventilation and perfusion to ensure optimum gas exchange across each unit ensure optimum gas exchange across each unit

This does not happen even in normal individuals where This does not happen even in normal individuals where V/Q ranges in different lung regions from 0.6 to 3.0, V/Q ranges in different lung regions from 0.6 to 3.0, mean overall is 1.0 mean overall is 1.0

In disease states, balance of ventilation and perfusion In disease states, balance of ventilation and perfusion may be disturbed further: may be disturbed further: ventilation-perfusion inequality - imbalances of V/Q ventilation-perfusion inequality - imbalances of V/Q intrapulmonary shunt: mixed venous blood not exposed to the intrapulmonary shunt: mixed venous blood not exposed to the

alveolusalveolus

Problems with Matching Pulmonary Problems with Matching Pulmonary Blood Flow and VentilationBlood Flow and Ventilation

In disease states, balance of ventilation and perfusion In disease states, balance of ventilation and perfusion may be disturbed further: may be disturbed further: ventilation-perfusion inequality - imbalances of V/Q ventilation-perfusion inequality - imbalances of V/Q intrapulmonary shunt: mixed venous blood not exposed to the intrapulmonary shunt: mixed venous blood not exposed to the

alveolusalveolus

HypoventilationHypoventilation

To prevent the development of respiratory acidosis, the To prevent the development of respiratory acidosis, the carbon dioxide produced each day (17,000 meq acid) carbon dioxide produced each day (17,000 meq acid) must be exhaled by the lungs at the same rate must be exhaled by the lungs at the same rate

The relationship among alveolar ventilation (VA), The relationship among alveolar ventilation (VA), carbon dioxide production (VCOcarbon dioxide production (VCO22) and the partial ) and the partial pressure of carbon dioxide in the blood (PaCOpressure of carbon dioxide in the blood (PaCO22) is ) is expressed using a modification of the Fick principle of expressed using a modification of the Fick principle of mass balance that quantitates VCOmass balance that quantitates VCO22 as the product of as the product of VA and the fractional concentration of COVA and the fractional concentration of CO22 in the in the alveolar gasalveolar gas

Diagnosis of Respiratory FailureDiagnosis of Respiratory Failure

History and Physical Examination History and Physical Examination patient symptoms patient symptoms physical examination physical examination

Laboratory TestsLaboratory Tests

Patient Symptoms in Respiratory FailurePatient Symptoms in Respiratory Failure

Mental function: headache, visual disturbances, Mental function: headache, visual disturbances, confusion, memory loss, hallucinations, loss of confusion, memory loss, hallucinations, loss of consciousness. consciousness.

Dyspnea (resting vs. exertional). Dyspnea (resting vs. exertional).

Cough, sputum production, chest pain.Cough, sputum production, chest pain.

Arterial Blood Gas Analysis Arterial Blood Gas Analysis

The most important lab test to subclassify The most important lab test to subclassify respiratory failure respiratory failure

Provides an indication of the duration and Provides an indication of the duration and severity of respiratory failure severity of respiratory failure

Gives 3 Types of Information: Gives 3 Types of Information: presence and degree of hypoxemia (PaOpresence and degree of hypoxemia (PaO22) ) presence and degree of hypercapnia (PaCOpresence and degree of hypercapnia (PaCO22) ) arterial Acid-Base Status (pH)arterial Acid-Base Status (pH)

HypoxemiaHypoxemiaReduction of partial pressure of oxygen in the blood Reduction of partial pressure of oxygen in the blood

Resting PaOResting PaO22 normally 75-80mmHg, 60mmHg lower normally 75-80mmHg, 60mmHg lower limit of safety limit of safety

Oxygenation failure considered if PaOOxygenation failure considered if PaO22 < 50-60mmHg < 50-60mmHg on FiOon FiO22 40% or greater 40% or greater

Decreases in PaODecreases in PaO22 Occur Secondary To: Occur Secondary To: intracardiac or intrapulmonary shunting of blood intracardiac or intrapulmonary shunting of blood V/Q mismatch V/Q mismatch alveolar hypoventilation alveolar hypoventilation

Alveolar gas equation is helpful in sorting out causes of Alveolar gas equation is helpful in sorting out causes of hypoxemiahypoxemia

HypercapniaHypercapnia

Hypercapnia in an increase PaCOHypercapnia in an increase PaCO22 > 50 mmHg. > 50 mmHg.

PaCOPaCO22 = KVO = KVO22 * VA * VA

VCOVCO22 (carbon dioxide) is produced by the (carbon dioxide) is produced by the

oxidative metabolism of carbon containing food oxidative metabolism of carbon containing food products. products.

Any increase in VCOAny increase in VCO22 or decrease in VA will or decrease in VA will

result in hypercapnia. result in hypercapnia.

Respiratory Failure Examples of Lung Respiratory Failure Examples of Lung vs. Pump Failurevs. Pump Failure

Disorders causing respiratory failure can Disorders causing respiratory failure can usually be divided into those causing lung usually be divided into those causing lung failure (impaired oxygenation) vs. pump failure failure (impaired oxygenation) vs. pump failure (hypercapnia). (hypercapnia).

Adult Respiratory Distress Syndrome (ARDS) is Adult Respiratory Distress Syndrome (ARDS) is an example of lung failure, drug overdose is an an example of lung failure, drug overdose is an example of pump failure.example of pump failure.

ARDS - Clinical CaseARDS - Clinical Case

43 year old respiratory therapists with asthma, develops 43 year old respiratory therapists with asthma, develops acute exacerbation and aspirates during endotracheal acute exacerbation and aspirates during endotracheal intubation. Following intubation, progressive severe intubation. Following intubation, progressive severe hypoxemia refractory to 100% Ohypoxemia refractory to 100% O22 develops. develops.

Lab Data Lab Data ABG on 100% FiOABG on 100% FiO22, shows PaO, shows PaO22 114, PaCO 114, PaCO22 32, pH 7.47 on VT 32, pH 7.47 on VT

600cc, RR 18. A-a gradient=56mmHg. 600cc, RR 18. A-a gradient=56mmHg. CXR shows diffuse alveolar infiltrates. CXR shows diffuse alveolar infiltrates.

Management Management mechanical ventilation, AC ventilation, high FiOmechanical ventilation, AC ventilation, high FiO22 with increasing with increasing

levels of PEEP to decrease shunting. levels of PEEP to decrease shunting. Aggressive use of bronchodilators to alleviate bronchospasm. Aggressive use of bronchodilators to alleviate bronchospasm. Diuresis, enteral feeding, DVT and GI bleed prophylaxis.` Diuresis, enteral feeding, DVT and GI bleed prophylaxis.`

Respiratory Failure: Pump Failure CaseRespiratory Failure: Pump Failure Case

Case: 24 year old white female injected heroin 1/2 Case: 24 year old white female injected heroin 1/2 hour prior to presentation and presents comatose hour prior to presentation and presents comatose with shallow irregular respirations. Needle tracks with shallow irregular respirations. Needle tracks are present, gag reflex is absent. are present, gag reflex is absent.

Labs: Labs: ABG shows PaO2 40, PaCOABG shows PaO2 40, PaCO22 80, and pH 7.01. Alveolar 80, and pH 7.01. Alveolar

- arterial gradient = 10mmHg. CXR - clear lungs. - arterial gradient = 10mmHg. CXR - clear lungs.

Therapy: Therapy: Endotracheal intubation assisted ventilation Naloxone Endotracheal intubation assisted ventilation Naloxone

infusioninfusion

Diffusion abnormalitiesDiffusion abnormalities

Factors influencing diffusionFactors influencing diffusion thickness of membranethickness of membrane ((inverseinverse))

areaarea ((linearlinear))

constant of diffusionconstant of diffusion pressure gradientpressure gradient ((linearlinear))

Vgas=A x D x P1 - P2

T

A: area of membraneD: constantT: thickness of membraneP1-P2: pressure gradient

Possible causes of abnormal diffusionPossible causes of abnormal diffusion

Increase the thickness or decrease of areaIncrease the thickness or decrease of area fibrotic fibrotic tissue or alveolar cell proliferationtissue or alveolar cell proliferation thickening of capillary membranethickening of capillary membrane interstitial edema, exudatinterstitial edema, exudateses intraalveolintraalveolarar edema edema or exudates or exudates

Shorter contact timeShorter contact time 1/31/3 is enough for the normal diffusion so is enough for the normal diffusion so PaO PaO22

normal generallynormal generally CO increases CO increases PaO PaO22 if diffusion is effected if diffusion is effected

FIOFIO22 (P (P11 - P - P22) )

Changes of Gas exchange by exerciseChanges of Gas exchange by exercise

60

at rest

CO

SummarySummaryAbnormal diffusionAbnormal diffusion::

PAOPAO22 norm normaall but but PaO PaO22 decreaseddecreased

P(A - a)OP(A - a)O22 >>10 10 mmmmHgHg

Usually triggered by exercise Usually triggered by exercise

FIOFIO22 ↑↑ improves improves

Rarely the cause of hypoxiaRarely the cause of hypoxia

Mechanical component of breathingMechanical component of breathing

Mechanisms influencing inspiration and Mechanisms influencing inspiration and expirationexpiration elasticityelasticity

Lung parenchymaLung parenchyma Cavity of chestCavity of chest

resistance of airwaysresistance of airways other forces against the mechanism of other forces against the mechanism of

respirationrespiration

Lung volumesLung volumes

Spirometer

TV: tidal volumeERV: expiratory reserve capacityRV: residual volumeVC: vital capacityFRC: functional reserve capacityTLC: total lung capacity

Measurement of lung volumesMeasurement of lung volumes

SpiromSpiromeeter – ter – RV can not be determinedRV can not be determined

bodybody plethysmograph plethysmograph

Inert gas dilution testInert gas dilution test

FRC FRC can be estimated. can be estimated. RV = FRC-ERV

TLC = RV + VC

Static expiratory pressure-volume curves

Disruption of alveolar wallsFRC , RV elasticity

Interstitial or infiltration problem FRC , RV , elasticity

Factors influencing the elastic recoilFactors influencing the elastic recoil

Surface tensionSurface tension (surfactant (surfactant -dipalmit-dipalmitooddyyllphophosfatidilsfatidilchcholin, olin, other other

lipids and proteinslipids and proteins-- produced by type produced by type II.II. alveolar cells alveolar cells

Tissue elasticityTissue elasticity ((amount of amount of elastin elastin and collagen)and collagen)

The importance of surface tension.

If two connected alveoli have the same surface tension, then the smaller the radius, the greater the pressure tending to collapse the sphere. This could lead to alveolar instability, with smaller units emptying info larger ones. Alveoli typically do not have the same surface tension because surface forces vary according to surface area, due to the presence of surfactant. Since the relative concentration of surfactant in the surface layer of the sphere increases as the radius of the sphere falls, the effect of surfactant is increased at low lung volumes. This tends to counterbal ance the increase in pressure needed to keep alveoli open at diminished lung volume and adds stability to alveoli which might otherwise tend to collapse info one another. Surfactant thus protects against regional col lapse of lung units, a condition known as atelectasis, in addition to its other functions.

Pathological conditionsPathological conditions

respiratory distress syndrome in newbornsrespiratory distress syndrome in newborns Inadequate biosynthetic pathwaysInadequate biosynthetic pathways Inactivation of surfactantInactivation of surfactant Pathologic mechanical forces used up Pathologic mechanical forces used up

surfactantsurfactant metabolic problems:metabolic problems: acid acidosisosis, hypox, hypoxiaia, ,

decreased venous circulationdecreased venous circulation

Alveoli collapse, TLC, RV and FRC, elastic effort

(ARDS)(ARDS) -atelectas-atelectasyy, , lunglung edema edema

sshhoocckk trauma: trauma: burningburning, , fat embolismfat embolism, , crash of lung tissue, crash of lung tissue,

water aspirationwater aspiration Infections - SepsisInfections - Sepsis Inhalation of toxic gasInhalation of toxic gas Overdose of drugsOverdose of drugs: barbitur: barbiturates, sates, salalyyccyyllatesates, heroin, , heroin,

tthhiazidiazidss MetabolitesMetabolites: ketoacid: ketoacidosesoses, urem, uremic toxinsic toxins OthersOthers: pancreatitis, DIC, amnion-emb: pancreatitis, DIC, amnion-embolismolism, paraquat-, paraquat-

toxicationtoxication

Adult Respiratory Distress SyndromeAdult Respiratory Distress Syndrome

Decreased in elasticityDecreased in elasticity

Elasticity of lung parenchyma decreasesElasticity of lung parenchyma decreases lung fibrosislung fibrosis emphysemaemphysema

Elasticity of chest cavity decreasesElasticity of chest cavity decreases obesityobesity Deformity of chest wallDeformity of chest wall (ankylo spondilitis, (ankylo spondilitis,

scoliosis)scoliosis)

Elastic effort increases, TLC, FRC.

Changes of airflowChanges of airflow

CentrCentral obstructionsal obstructions Acute obstruction between the Acute obstruction between the glottis glottis andand

carinacarina.. Allergic reaction triggered by bite of Allergic reaction triggered by bite of insectsinsects

Slowly developing chronic forms:Slowly developing chronic forms: Constant obstruction e.g. tumorConstant obstruction e.g. tumor Temporary Temporary Laryngeal spasmLaryngeal spasm

Maximal expiratory volumeMaximal expiratory volume

Measures the mechanical status of Measures the mechanical status of airwaysairways

FVC - Forced Vital CapacityFVC - Forced Vital Capacity expirationexpiration::

PPalvalv = P= Pplpl + P + Pelel Ppl : pleural pressure, muscle workPel : pressure of elasticity

Important: The expiratory flow at the ¾ of the vital capacity dose notdepend on muscle forces, elasticity dependent

ForcedForced Vital CapacityVital Capacity(FVC)(FVC)

V (m L )

V (

L/m

in)

.

2 2

-22

4 5 0 0

E

I

V (m L )

V (

L/m

in)

.

2 2

-22

4 5 0 0

E

I

F ixá lt lég ú tio b stru ctio

N o rm á l

T érfo g a t-á ra m lá si g ö rb ék

V (m L )

V (

L/m

in)

.

2 2

-22

4 5 0 0

E

I

V (m L )

V (

L/m

in)

.

2 2

-22

4 5 0 0

E

I

V á lto zó ex tra th ora ca lislég ú ti o b stru ctio

V á lto zó in tra th ora ca lislég ú ti o b stru ctio

V (m L )

V (

L/m

in)

.

2 2

-22

4 5 0 0

E

I

V (m L )

V (

L/m

in)

.

2 2

-22

4 5 0 0

E

I

A stm a

E m p h ysem a

K e z e lé s e lő tt

K e z e lé s u tá n

Asthma

Volume-time curvesVolume-time curves

FVC plotted this way usuallyFVC plotted this way usually

FEF25-75

Functions of breathing musclesFunctions of breathing muscles

DiaphragmDiaphragm: : tidal volume (breathing at tidal volume (breathing at rest)rest)

IntercostaliIntercostali muscles muscles outerouter: : inspirationinspiration innerinner: : expirationexpiration

Scalenus Scalenus musclemuscle ((lifting ribslifting ribs)) tidal breathingtidal breathing

SternocleidomastoidSternocleidomastoid muscle muscle – – lifting the lifting the sternum sternum ((forced respirationforced respiration))

Frontal longitudinal musclesFrontal longitudinal muscles - - ((forced forced respirationrespiration))

MMechaniechanism of respiratory musclessm of respiratory muscles

Length - stretch correlationLength - stretch correlation Inspiratory muscles have the highest stretch at rest Inspiratory muscles have the highest stretch at rest Expiratory muscles have the highest stretch at Expiratory muscles have the highest stretch at TLCTLC

HyperinflatioHyperinflationn obstruobstructionction inflatesinflates efficacy increases during efficacy increases during

expiration; however more work needed during inspirationexpiration; however more work needed during inspiration

OO22 equilibrium (substitutedequilibrium (substituted//needed)needed) Similarly to brain and heart muscles needs oxygen. The Similarly to brain and heart muscles needs oxygen. The

inspiratory muscles are more sensitive because there are no inspiratory muscles are more sensitive because there are no

other help other help hypercapnhypercapnyy, hypox, hypoxemyemy

Evaluation of mechanical forcesEvaluation of mechanical forces

SpiromSpiromeeterter FVC, FEVFVC, FEV11, FEF, FEF25-7525-75,,

Diseases influence the mechanical forces Diseases influence the mechanical forces of lung decrease air ventilation and causeof lung decrease air ventilation and cause ObstruObstructive lung diseasesctive lung diseasesDecreases the amount of air holding unit Decreases the amount of air holding unit of lung causeof lung cause RestriRestrictive lung diseasesctive lung diseasesMixed form Mixed form ((fewfew))

FEV1

FVC

Restrictive pulmonary diseasesRestrictive pulmonary diseases FVCFVC, FEV, FEV11/FVC norm/FVC normaall

Obstructive pulmonary diseases,Obstructive pulmonary diseases, asthma, emphysemaasthma, emphysema etc. etc. FVCFVC, FEV, FEV11/FVC/FVC

““COPD”COPD”

EmphysemaEmphysema

Chronic BronchitisChronic Bronchitis

AsthmaAsthma

Cystic FibrosisCystic Fibrosis

Interstitial Lung Disease (ILD).Interstitial Lung Disease (ILD).

Obstructive Pulmonary DiseasesObstructive Pulmonary Diseases

Chronic Obstructive Pulmonary Chronic Obstructive Pulmonary Disease (COPD) Disease (COPD)

COPD is an accumulation of symptoms COPD is an accumulation of symptoms produced by respiratory diseases that produced by respiratory diseases that result in a diagnosis if COPD.result in a diagnosis if COPD.

Chronic bronchitis and emphysema.Chronic bronchitis and emphysema.

COPD is a respiratory disorder or COPD is a respiratory disorder or syndrome rather than a disease state.syndrome rather than a disease state.

COPDCOPD

Fourth leading cause of death in US.Fourth leading cause of death in US.

Approximately 18 million individuals. Approximately 18 million individuals.

Results in $440 billion in health care Results in $440 billion in health care costs annually.costs annually.

Surge of COPD in recent years.Surge of COPD in recent years.

COPD SymptomsCOPD Symptoms

COPD is characterized by two concepts:COPD is characterized by two concepts: Decreased expiratory air flow pressure, andDecreased expiratory air flow pressure, and Increased resistance to expiratory air flow.Increased resistance to expiratory air flow.

These problems are caused by airway These problems are caused by airway obstruction, determined by specific obstruction, determined by specific respiratory disease.respiratory disease.

Chronic Obstruction Pulmonary Chronic Obstruction Pulmonary DiseasesDiseases (COPD) (COPD)

Increased bIncreased bronchialronchial fluids fluids inflammations, thickening of brochial wall, inflammations, thickening of brochial wall,

hypertrophy of smooth muscleshypertrophy of smooth muscles

Thickening of Thickening of AcinAcini, discrepancy between i, discrepancy between protease – antiproteasesprotease – antiproteases alveol alveolar ar damagedamageNarrowing of small airways, inflammation, Narrowing of small airways, inflammation, fibrosisfibrosis resistance of airways increaseresistance of airways increaseUsually mixed formUsually mixed form

HHypercapnypercapnia in COPDia in COPD

PaCO2 = K x CO2 produced

alveolar gas exchange

PaCO2 = K xBMR + respir work

respir volume - residual

Respiratory work less then 2 % of BMR. can exceed 20%, in pathologic conditions.Hyperventilation can not decrease PCO2, because the rate of CO2

production is more

Progression of COPD and AsthmaProgression of COPD and Asthma

Normal

Failure

Time in Weeks, Months, Years

Possible compensatory mechanismsPossible compensatory mechanisms

With and increasedWith and increased a pCO a pCO22

alveolalveolaar hypoventilr hypoventillationlation pCO pCO22 CSF CSF

[HCO[HCO33]]-- stimulation decreasesstimulation decreases hypoxia, hypoxia,

cyanosis cyanosis pulmon pulmonalal hypertensio hypertensionn, , polycythaemia, cor pulmonale, edema polycythaemia, cor pulmonale, edema “Blue bloater”“Blue bloater”

TachTachyypnoe pnoe pCO pCO2, 2, PACOPACO22 norm normaal, nl, nonon

cyanotic, cyanotic, there is nothere is no polycythaemia polycythaemia nornor edema edema “Ping puffer”“Ping puffer”

Chronic BChronic Bronchitisronchitis

Chronic coughChronic cough associated with sputum production associated with sputum production more than more than 90 days 90 days on on 2 2 successive yearssuccessive years. Rule out. Rule out TBC, tumor, congestiveTBC, tumor, congestive heart heart failurefailureCauseCause:: smoking, smoking, air pollution. Occupational exposure, air pollution. Occupational exposure, etc.etc.

Pathologic changes:Pathologic changes: Increase in mucous glands in airwaysIncrease in mucous glands in airways Mucus accumulation in small airwaysMucus accumulation in small airways Small diameterSmall diameter,, <2mm, airways narrowing<2mm, airways narrowing Recurrent inflammations, infection, and subsequent scaring in the Recurrent inflammations, infection, and subsequent scaring in the

terminal airwaysterminal airways R Rawaw (resistance) (resistance) Blue bloater typeBlue bloater type: Hypoxaemi: Hypoxaemicc, , right heart failureright heart failure

(clinical diagnosis)

EmphysemaEmphysema

Abnormal permanent enlargement of the Abnormal permanent enlargement of the airspaces distal to the terminal bronchiole, with airspaces distal to the terminal bronchiole, with destruction of the wall,without obvious fibrosisdestruction of the wall,without obvious fibrosis

Site of injury is the septa-Site of injury is the septa- Elimination of pulmonary capillary bedElimination of pulmonary capillary bed Increase volume in acinus, with the development of Increase volume in acinus, with the development of

blebs (air spaces near pleura) and bulae (large air blebs (air spaces near pleura) and bulae (large air spaces)spaces)

Mechanical decrease in airway caliber Mechanical decrease in airway caliber (compression of acini)(compression of acini)

Loss of elastic recoilLoss of elastic recoil

TTypes of Emphysemaypes of Emphysema

CentrilobulCentrilobulaar (centriacinr (centriacinaar) emphysemar) emphysema Upper lobes and superior segments of the lower lobesUpper lobes and superior segments of the lower lobes.. Highly associated with smokingHighly associated with smoking

Panlobular (panacinPanlobular (panacinaar) emphysemar) emphysema Entire acinus, even in its earliest stages. Associated with Entire acinus, even in its earliest stages. Associated with

homozygous alpha1-antitrypsin deficiencyhomozygous alpha1-antitrypsin deficiency

Distal aciner (periacinDistal aciner (periacinaar, paraseptal, subpleural) r, paraseptal, subpleural) emphysemaemphysema Involves distal alveolar sacs and ducts, usually in the Involves distal alveolar sacs and ducts, usually in the

upper lobes and often subpleurally or along fibrous upper lobes and often subpleurally or along fibrous interlobular septa. Typically seen in a young adult with interlobular septa. Typically seen in a young adult with history of spontaneous pneumothoraxhistory of spontaneous pneumothorax

Emphysema

Pathogenesis of EPathogenesis of Emphysemamphysema

Inbalance between naturally occuring Inbalance between naturally occuring proteases and atiproteasesproteases and atiproteases Alveolar destruction occurs by the proteases Alveolar destruction occurs by the proteases

liberated from neutrophils, elastase liberated from neutrophils, elastase Smoking inhibitsSmoking inhibits 11--antitrypsinantitrypsin General alveolar General alveolar hyperventilatiohyperventilatio

““Pink puffer type”Pink puffer type”

EmphysemaEmphysemaPathogenesisPathogenesis

AsthmaAsthma

Reversible air flow obstruction manifested by Reversible air flow obstruction manifested by wheezing and caused by combinaton of airway wheezing and caused by combinaton of airway mucosal edema and inflammationmucosal edema and inflammation Increased secretions and smooth muscle constriction.Increased secretions and smooth muscle constriction.

Inflammatory Mechanism in AsthmaInflammatory Mechanism in Asthma Early (<15 min), Early (<15 min), IgEIgE-mediated-mediatedóó and late and late (4 (4-8 h), -8 h),

mechanism unknownmechanism unknown Multiple cells (Multiple cells (macrophagmacrophageses, eosinophil, eosinophilss, , hystiocytes andhystiocytes and

TT--lymphocytlymphocytes) and many mediators (cytokines, groth es) and many mediators (cytokines, groth factors, enzymes and superoxides) are involed following factors, enzymes and superoxides) are involed following various airway challenges (antigenes, chemical exposure, various airway challenges (antigenes, chemical exposure, exercise). At least six separate steps in this complex chain exercise). At least six separate steps in this complex chain of events have been identifiedof events have been identified

Allergen

Mast Cell

Degranulates

HistamineBradykininLeukotriene

ProstaglandinsThromboxane

Chemotactic factor

Releases

Mediators

*Airway smooth muscle contraction

*Increased vascular permeability

*Increased mucoussecretions

Peden, 2003

HistamineBradykininLeukotriene

ProstaglandinsThromboxane

Recruits

Eos

Eosinophils release

Mediators

Trashes Airway Epithelium and destroys cilia!!!

Loss of epithelium... 1. Exposes nerve endings2. Increased cytokine production3. More inflammation.4. Bronchospasm—inc. parasympathetic

Late asthmatic response—4-8hrs laterLate asthmatic response—4-8hrs laterPeden, 2003

Lung RemodelingLung Remodeling

Jeffery Am J. Resp. Crit Care Med. 2001

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3

4

5

6

7

8

9

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V T V T

V T

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A stm a sú ly osb o d á saSeverity of Asthma

Total

dilatation

Pathophysiology of AsthmaPathophysiology of AsthmaTriggeringTriggering spec. antigspec. antigeen n IgE IgE h hystiocytesystiocytes tryptase, PGDtryptase, PGD22, LTC, LTC44

SignalingSignaling ccyytokintokinss T T--lymphocytlymphocyteses ( (intermediate messengerintermediate messenger) ) IL IL-2 -2 IL-2 IL-2

receptors receptors kemotaxis, kemotaxis, activation of immunsystemactivation of immunsystem IgE IgE

MigrMigrationation macrophagmacrophageses, eosinophil, eosinophilss, lymphocyt, lymphocyteses, monocyt, monocyteses LTB4, PAF, IL-LTB4, PAF, IL-

5, IL-8; 5, IL-8; ILIL-1, TNF-1, TNF ELAM-1, ICAM-1, Mac-1 adhesion molecules ELAM-1, ICAM-1, Mac-1 adhesion molecules inflammationinflammation

Inflammatory Cell ActivationInflammatory Cell Activation ccyytokinetokiness LTC4 LTC4 brochospa brochospasmsm, , increased increased permeabilpermeabiliittyy

Inflammation Causes BronchoconstrictionInflammation Causes Bronchoconstriction Damage of Damage of epitepithelial cellshelial cells az antig az antigen penetrates into deeper en penetrates into deeper

layerlayer strongerstronger bronchospa bronchospassm, m, smooth muscle cell smooth muscle cell ploriferationploriferation. . Inhibits mediators inducing dilatation Inhibits mediators inducing dilatation (PGE(PGE22, , NO)NO)

ResolutioResolutionn Although usually the episodic disease fully reversible, chronic form Although usually the episodic disease fully reversible, chronic form

becoming evidentbecoming evident

Pathophysiology of Asthma

BronchiectasisBronchiectasisPathogenesisPathogenesis

Bronchial obstruction Bronchial obstruction → Atelectasis→ AtelectasisDilatation of walls of patent airwaysDilatation of walls of patent airwaysInfection → Bronchial wall inflammation Infection → Bronchial wall inflammation → weakened walls → further dilation→ weakened walls → further dilationCystic fibrosis: squamous metaplasia Cystic fibrosis: squamous metaplasia with impaired mucociliary action, with impaired mucociliary action, infection, necrosis of bronchial and infection, necrosis of bronchial and bronchiolar wallsbronchiolar wallsKartagener’s syndrome: absent dynein Kartagener’s syndrome: absent dynein arms in cilia → lack of ciliary activityarms in cilia → lack of ciliary activity

Function of Cytoplasmic DyneinFunction of Cytoplasmic Dynein

BronchiectasisBronchiectasisMorphologyMorphology

GrossGross

Usually both lower Usually both lower lobeslobesMay be localisedMay be localisedDilated airwaysDilated airways

CylindroidCylindroid

FusiformFusiformSaccularSaccular

Cystic pattern on cut Cystic pattern on cut surface of lungssurface of lungs

HistologyHistologyAcute and chronic Acute and chronic inflammationinflammationDesquamation of Desquamation of epitheliumepitheliumNecrotising ulcerationNecrotising ulcerationSquamous metaplasiaSquamous metaplasiaNecrosis Necrosis → lung → lung abscessabscessFibrosisFibrosis

BronchiectasisBronchiectasisComputed TomographyComputed Tomography

BronchiectasisBronchiectasisGrossGross

BronchiectasisBronchiectasisHistologyHistology

BronchiectasisBronchiectasisComplicationsComplications

PneumoniaPneumonia

Lung abscessLung abscess

EmpyemaEmpyema

SepticaemiaSepticaemia

Cor pulmonaleCor pulmonale

Metastatic cerebral abscessesMetastatic cerebral abscesses

Secondary AmyloidosisSecondary Amyloidosis

Cystic FibrosisCystic Fibrosis

Genetic deficiency disease characterized Genetic deficiency disease characterized by recurrent respiratory tract infections.by recurrent respiratory tract infections.

Estimated 1 in 20 individuals carry trait Estimated 1 in 20 individuals carry trait for CF.for CF.

Typically diagnosed by age of 6 months.Typically diagnosed by age of 6 months.

Limits life expectancy to ~29 years.Limits life expectancy to ~29 years.

Cystic FibrosisCystic Fibrosis

Improper cellular retention of sodium Improper cellular retention of sodium chloride – lungs, pancreas. chloride – lungs, pancreas.

NaCl draws water from airways, NaCl draws water from airways, resulting in dry mucus.resulting in dry mucus.

Airway obstruction, resulting in Airway obstruction, resulting in respiratory infection and tissue damage.respiratory infection and tissue damage.

Cystic FibrosisCystic Fibrosis

Individuals can go asymptomatic until Individuals can go asymptomatic until adolescence.adolescence.

Later trigger, however, indicates more Later trigger, however, indicates more rapid decline in health.rapid decline in health.

Typically will also involve heptatic Typically will also involve heptatic system, including cirrhosis and jaundice.system, including cirrhosis and jaundice.

DiagnosisDiagnosis

PE and history of respiratory infections during PE and history of respiratory infections during infancy/childhood.infancy/childhood.

Sweat test – increased sodium marker.Sweat test – increased sodium marker.

DNA analysis.DNA analysis.

Currently, genetic engineering is attempting to Currently, genetic engineering is attempting to develop way to modify gene.develop way to modify gene.

PathomechaniPathomechanissmmClCl-- transport abnormality of bronchial cells on the luminal sitetransport abnormality of bronchial cells on the luminal site

Cl- diffuses into the cells normally. Influenced Cl- transport sodium accumulationViscosity of mucus increases, plugging airways infections (Pseudomonas aeruginosa) Respiratory failure, brochiectasis death

11 – – antitrypsin antitrypsin DeficiencyDeficiency (AAT) (AAT)

AutosomalAutosomal disease (more than 75 allels have been disease (more than 75 allels have been identified)identified), , decreased amount of antitrypsin decreased amount of antitrypsin produced. Aproduced. Antiprotentiprotease activity decreases ase activity decreases elastase activity elastase activity ↑↑ emphysema emphysema by age of by age of 4 40, 0, develops earlier in smokers.develops earlier in smokers.

Interstitial Lung DiseaseInterstitial Lung Disease

Inflammation of the alveolar walls inside Inflammation of the alveolar walls inside the lungs.the lungs.

Almost exclusively from industrial Almost exclusively from industrial irritants and agricultural byproducts.irritants and agricultural byproducts.

Numerous conditions coined in Numerous conditions coined in occupational health to describe ILD.occupational health to describe ILD.

Black lung – coal dust from mining.Black lung – coal dust from mining.Farmer’s lung – fungi exposure in moldy hay.Farmer’s lung – fungi exposure in moldy hay.Bird breeder’s lung – inhalation of avian Bird breeder’s lung – inhalation of avian proteins.proteins.Silicosis – inhalation of silicon dust.Silicosis – inhalation of silicon dust.Asbestosis – inhalation of asbestos.Asbestosis – inhalation of asbestos.

Exposure to wood products, detergents, metals, Exposure to wood products, detergents, metals, and other animal proteins.and other animal proteins.

Interstitial Lung DiseaseInterstitial Lung Disease

DiagnosisDiagnosis

PE.PE.

Evaluation of job site.Evaluation of job site.

X-ray of lungs.X-ray of lungs.

SpirometrySpirometry

PathomechanizmusPathomechanizmus

Interstitium is involvedInterstitium is involved. . Injury occurs initially to thype I alveolar epitelial cells or Injury occurs initially to thype I alveolar epitelial cells or capillary endotheliumcapillary endothelium edema, haemorrhage edema, haemorrhage fibrin fibrin is is deposited along alveolar wallsdeposited along alveolar walls (hyalin membrán) (hyalin membrán) Inflammatory phaseInflammatory phase infiltration of infiltration of neutrophilneutrophilss, , macrophagmacrophages andes and lymphocyt lymphocyteses c cyytokinetokiness influence influence the subsequent intensity and duration of disease process the subsequent intensity and duration of disease process and fibrosis and repair processand fibrosis and repair processInflammatory process subsides, proliferation of type II Inflammatory process subsides, proliferation of type II alveolar cells and organization of the fibrinous exudate alveolar cells and organization of the fibrinous exudate occuroccur collagen is deposited collagen is deposited distortion of lung distortion of lung architecture and enlargement of alveolar air spacesarchitecture and enlargement of alveolar air spacesSubsequent inflammatory process promote lung damageSubsequent inflammatory process promote lung damage

This should be enough for to

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