clinical pulmonary pa tho physiology

Kit Delgado – [email protected] Clinical Pulmonary Pathophysiology Obstructive Disease Clinical Presentation Chest Imaging Labs / Blood

Gases Pulmonary Function Tests Pathophysiology Mechanisms Management

Asthma

Dyspnea, orthopnea, anxiousness. May be sustained in late phase.

Allergy or non-

allergy

Rapid pulse, pulsus paradoxus (fall in pulse pressure during inspiration) may be present

Pathogenesis: Diffuse Disease of Conducting Airway

Hyperinflation, otherwise normal

PaO2 down during attack

PaCO2 normal or low until late in disease

Spirometry (Obstructive) During attack all

indices of expiratory flow are significantly reduced

FVC also reduced because the airways close prematurely towards the end of a full expiration

Pc20: 20% fall in FEV1 when administered irritant

Flow-volume curve:

Typical obstructive pattern, but no scooped out appearance

Static Lung Volumes:

Increased during attack (RV, FRC very high)

FRC measurement value (body plesthysmography> helium dilution)

Ventilatory Capacity and Mechanics Bronchospasm increases resistance in all

airways Increased RV caused by premature airway

closure during full expiration High TLC has advantage of reducing

resistance by increasing radial traction of airways

Gas exchange

Arterial hypoxemia common – caused by V/Q mismatch. Uneven ventilation.

Physiological dead space and shunt high.

But no pure shunt, surprising considering there is mucus plugging (Probably from collateral ventilation).

PaCO2 prevented from rising by increasing

ventilation to alveoli in face of V/Q mismatch (stimulation of peripheral chemo receptors by mild hypoxemia or by intrapulmonary receptors)

Status asthmaticus: PaCO2 rises pH falls

sign of impending respiratory failure. Need mechanical ventilation.

Diffusion capacity normal

Bronchodialators Some open

airways at mild expense of decreasing PaO2 slightly. From relief of vasoconstriction of poorly ventilated areas.

Corticosteroids Candidate target molecules for new therapies:

mAb Ige LTD4 PGD2 PAF Substance P MBP, ECP Ach Mast cell

secretory products: serine protease tryptase

2Clinical Presentation Chest Imaging Labs / Blood


Cystic Firbosis

Child cough sputum weight loss School/work

absenteeism Dyspnea Decreased exercise

tolerance Crackles Clubbing Kyphosis

Pathogenesis: Diffuse Disease of Conducting Airway

CXR: can look fairly

normal hyperinflation as disease

progresses

bronchiectasis

older pts. pneumothorax

CT:

looks much more abnormal than CXR

Bronchoscopy:

mucus in airways

Increasing hypoxemia beginning in mild disease

Spirometry FEV1 starts going down

in moderate to severe disease

FEF25-75 starts going down in mild disease

These do not improve with bronchodialators!

Lung volumes

VC starts going down in moderate disease

Increasing RV/TLC beginning in mild disease

A-a gradient widened Compliance down Flow rates at low volumes down Slope of phase III nitrogen washout up Physiological dead space up Exercise tolerance down

Complications

Atelctasis Hemoptysis Pneumothorax Cor Pulmonale

Treatment: Antibiotics

(aerosolized key) Airway clearance

(chest physical therapy, flutter device, DNAase - mucolytic, anti-inflammatory)

Nutrition

3 Clinical Presentation Chest Imaging Labs / Blood


COPD Emphysema Type A (“Pink Puffer”)

Increasing dyspnea over years

Little or no cough No cyanosis Quiet breath sounds Normal Jugular

venous pressure Pathogenesis : Destruction of Alveolar Wall Chronic Bronchitis (+Emphysema) Type B (“Blue Bloater”)

increasing dyspnea over years

frequent cough with sputum

often cyanosis May have rales,

rhonci May have raised

JVP May have

peripheral edema Pathogenesis: Diffuse Disease of Conducting Airway

Marked chest expansion

Translucent lungs

Attenuated peripheral vessels

Normal Moderate or

no increase in chest volume

PaO2 slightly depressed

PaCO2 normal

PaO2 very low

PaCO2 often raised

Spirometry (Obstructive): FEV1 reduced FEV1/FVC reduced FEF25-75: reduced

Flow volume curve:

expiration: grossly abnormal, “scooped out appearance”

inspiration fairly normal Lung Volumes:

FVC reduced TLC, RV, FRC

increased Value on body

plesmography > gas dilution (slow equilibration process in poorly ventilated areas)

Ventilatory Capacity and Mechanics Airways close prematurely at abnormally high

lung volume Elastic recoil: reduced in emphysema

increase in TLC; normal in Bronchitis Airway resistance: increased

Gas exchange

V/Q mismatch inevitable, with or without CO2 retention. Due to disorganization of lung architecture uneven ventilation, and uneven blood flow. Compensated for by collateral ventilation and hypoxic vasoconstriction.

A-a gradient always increased, esp. in patients with chronic bronchitis

Dead space particularly increased in

emphysema

Shunt seen in chronic bronchitis

No diffusion abnormality in emphysema

On exercise, the PaO2 may fall or rise – depending on ventilation or cardiac response

If PaCo2 rises, pH will fall Resp. acidosis.

May be compensated for by retaining bicarb in chronic conditions.

Pulmonary Circulation

Pulmonary artery pressure may rise with severe disease (destruction of pulmonary vasculature; hypoxic vasoconstriction)

Cor pulmonale --> RV dilation (esp. in Type B patients)

Control of Ventilation

One reason for CO2 retention increased work of breathing due to increased resistance

Minute ventilation increased



Tracheal Obstruction Inspiratory and expiratory stridor from:

Inhaled foreign body, or

Stenosis after indwelling tracheaostomy tube, or

Compression by enlarged thyroid

PaO2 down PaCO2 up

Flow-Volume Curve abnormal expiration

AND inspiration

Hypoventilation No response to bronchodialators

Bronchial Obstruction

Inhalation of foreign body (size of peanut), or

Bronchial tumor, or Enlarged

surrounding LN

In inhalation of object, Right lung affected more than left (due to more direct path from trachea)

Enlarged LN, also more likely to cause obstruction on right (anatomy)

Collapsed lobe may be visible

PaO2 down

Adminster 100% O2 look at A-a gradient = most sensitive test

Absorption atelectasis may occur (b/c sum of partial pressure in mixed venous blood less than in alveolar gas)

Perfusion of unventilated lung reduced by hypoxic vasoconstriction

Infection may follow localized obstruction lung abcess

5Restrictive Disease Clinical Presentation Chest Imaging Labs / Blood


Interstitial Lung Diseases Signs, Sx:

Dyspnea with exertion

Persistent, non-productive cough

Hx:

Occupational, Drug, Family history, Respiratory, illness, Non-resp. illness

PE:

Tachypnea Tachycardia Crackles Clubbing

Pathogenesis: Diffuse thickening of alveolar wall

Alveolar filling

Interstitial infiltrates: linear; nodular; reticulonodular; honeycomb

PaO2 and PaC02 are reduced and pH is normal

Hypoxemia mild at rest until disease is advanced or during exercise

Spirometry (Restrictive): FVC reduced FEV1/FVC = normal, or

high FEF25-75 = normal, or

high Flow-volume curve:

downslope = higher than normal

Lung Volumes:

All are reduced, relative proportions preserved

Pressure-Volume Curve:

Displaced downward DLCO

Reduced

Ventilatory Capacity and Mechanics Findings consistent with fibrosis of alveolar

walls Stiff lungs with decreased expansile

capacity; airway resistance normal (reduced lung volumes, preservation of flow rates, small tidal volumes, resting tachypnea)

Very negative intrapleural pressure at TLC Gas Exchange

Elevated A-a gradient At rest:

V/Q mismatch primary cause of hypoxemia (1 b/c transit-time enough diffusion = normal, 2 b/c disorganization of the architechture)

Low PaCO2 caused by increased ventilation (tachypnea)

Arterial pH normal or high, may fall in respiratory failure

Exercise: V/Q mismatch + diffusion impeded (not

enough time for gas transit to capillary) High ventilation PaO2 fall, PaCO2 fall

respiratory alkalosis Pulmonary Circulation

Increased pulmonary vascular resistance especially during exercise – due to interstitial fibrosis

Control of Ventilation

Increased traction of airways of lung may cause J-receptors to fire

Increased work of breathing- compensated for tachypneic brathing - reduced maximal voluntary ventilation

6Clinical Presentation Chest Imaging Labs / Blood


Pneumonia Pulmonary (alveolar edema) Pulmonary hemmorhage Hyaline membrane disease of newborn Pathogeneis: Diseases of the Acini and Intersitium

Opaque blotches, once there’s fluid replacing air in the alveoli

PaO2 down PaCO2 down

Spirometry: Resistance to air flow

unaltered Lung Volumes

Decreased Administered 100% 02

Doesn’t raise PaO2!

Ventilatory Capacity and Mechanics Reduced compliance and filling of air

spaces with fluid, decreased lung volumes Minute and alveolar ventilation increased by

J-receptor stimulation and hypoxemia Gas Exchange

PaO2 reduced due to increase in physiological shunt. (Due to replacement of alveolar air with fluid).

PaCO2 reduced because of compensatory hyperventilation

V/Q mismatch, and diffusion problems do not play a role in these diseases

Pulmonary embolism Risk factors: vein wall injury, stasis, hypercoagulability Sx: Dyspnea, tachypnea, sometimes expiratory wheezes Small emboli:

Frequently unrecognized

Repeated emboli may result in pulmonary hypertension (2%)

Medium-sized emboli

Sometimes pleuritic pain, dyspnea, slight fever

Hemoptysis Pleural friction rub

Massive emboli

Hemodynamic collapse with shock, pallor, central chest pain

Small:

Right ventricular hypertrophy (after repeated emboli pulmonary hypertension)

Medium

Normal May see

shadow of infarction

PaO2 down PaCO2 down

Ventilatory Capacity and Mechanics Changes may occur immediately

Compliance: Falls within a minute. Characteristic of uneven distal airway constriction. (Same mediators as vasoconstrcition).

Alveolar stability: aveoli closing distal to

airway constriction further reduce compliance

Airway resistance: airways that ventilate totally occluded vessel see very low PaCO2 vagal mediated bronchoconstriction increase in airway resistnace wheezing in some patients

Dyspnea: from increased work of breathing

due to decreased lung compliance (major), and increased airway resistance (minor)

Ventilation: Tachypnea – rapid shallow

breathing caused by J-receptor stimulation (not from chemorector mediated hypoxemia – this contributes to dyspnea).

Gas Exchange Hypoxemia develops rapidly. A-a gradient widening proportional to magnitude of embolic event.

V/Q mismatch = major reason. Heterogeneous distribution of ventilatory abnormalities

Shunt: continued ventilation of unperfused

areas accounts for 1/3 of A-a gradient

7 Hypotension with

rapid weak pulse, and JVP increase

Sometimes fatal

widening.

Diffusion: doesn’t play a role.

Low PaCO2 from hyperventilation respiratory alkalosis (from activation of irritant and J-receptors).

Pulmonary Circulation

Pulmonary hypertension (mechanical obstruction + release of vasoactive substances - Histamine).

Right Ventricle

In massive embolus immediate dilation, possibility of failure

Sustained Pulmonary Hypertension Progressive dyspnea with episodes of syncope during exertion From: Increase in LAP Increase in Pulmonary blood flow (ex. Congenital heart disease) Increase in pulmonary vasculature resistance lung disease:

Vasoconstriction (V/Q mismatch : chronic bronchitis, CF, acute bronchiolitis, asthma ; Hypoventilation)

Anatomic Restriction: (Extravascular: ILD’s; Intravascular: pulmonary vasculitis, schisto, filariasis, tumor emboli, sickle cell)

Combo of two: (1st group: emphysema, healed TB, anthrosilicosism; 2nd group: PE)

RV hypertrophy

PaO2 normal or low

PaCO2 low if hyper-ventilating

Ventilatory tests usually normal

Ventilatory Capacity and Mechanics: Dyspnea with exertion

Lung compliance: decreased progressively as the hypertensive process intensifies

Airway resistance: not increased during this

process

Ventilation: Tachypnea – rapid shallow breathing – during exertion.

Gas Exchange: Moderate widening of the A-a gradient.

Diffusion Abnormality: major cause of hypoxemia (from underlying interstitial abnormalities and arteriopathy).

As the flow through pulmonary vasculature

becomes limited drop off in CO syncope Pulmonary Circulation

Loss of microcirculation and arteriopathy b/c increase of resistance to flow

May result in systemic levels of blood pressure in pulmonary vasculature bed

Right Ventricle

RV hypertrophy increases with sustained and progressive pulmonary hypertension

Drops in CO may lead to syncope, chest pain Tachyarrthmias and sudden death are

common

8Acute Respiratory Failure Clinical Presentation Chest Imaging Labs / Blood


Acute Hypoxic Respiratory Failure (AHRF – Type 1) “Water, blood, or pus”

air space flooding Increase in Shunt flow

Low PaO2 Normalized

PaCO2

V/Q mismatch Most common etiology of depressed PaO2

clinically Increased Shunt Flow

This is the major gas exchange abnormality of ARDS (can be viewed as extreme V/Q mismatch. However, results in admixture of blood that isn’t ventilated at all therefore won’t respond to 100% O2.) From fluid filled alveolar spaces.

Diffusion Abnormality

Even when it exists, contribution to hypoxia is negligible unless it falls below 20%. This level of dysfunction could play a role in ARDS and COPD

Alveolar Hypoventilation

If no widening of A-a gradient, then not a gas exchange abnormality as above.

Treat airway obstruction and/or chest infection

Administration of

long-term O2 therapy often required

Ventilatory Respiratory Failure (Type II) Increased load, increased effort, decreased drive decrease in ventilation

Low PaO2 High PaCO2

Respiratory drive dysfunction: Drug OD, CVA, tumor, peripheral receptor

dysfunction Misuse of O2 therapy: (ex. COPD patient

developed CO2 retention over several months compensated respiratory acidosis

therefore respiratory drive now from hypoxemia gets infection given 100% O2 abolishes drive 100% O2 discontinued profound hypoventilation.) (Can also get worsening of the V/Q mismatch with lifting of hypoxemic vasoconstriction).

Neuromuscular disease

Guillan-Barre, MG, polio, spinal trauma, botulism, ALS, myositis

Chest Wall/Pleural Disease

Trauma (flail chest), kyphoscoliosis, massive pleural effusion, pneumothorax

Airway obstruction

Upper airway, stenosis, tumor Peripheral airway disorders

Asthma, anaphylaxis, COPD, CF, foreign body

Often responds to general measures directed at the airway obstruction or infection

Mechanical

ventilation frequently required



Adult Respiratory Distress Syndrome Associated with some severe underlying medical or surgical illness not connected to the lung (ex. Hemorrhagic shock after accident treated with fluid replacement) 2 days following trauma increase in RR and fall in PaO2, PaCO2 severe hypoxemia mortality 50% Pathogenesis: diffuse alveolar damage alveolar capillary permeability

Clouding seen in chest radiograph progresses to uneven opacification

Both fall drastically 2 days after incident - PaO2 (40), PaCO2 (20)

Ventilatory Capacity and Mechanics Lung becomes very stiff (alveolar edema) Decreased lung volume

Gas Exchange

Marked V/Q mismatch Increase in Shunt flow (50% or more)

Must be put on ventilator with high FIO2 prognosis not good when high shunt flow present

Stimulation of J receptors allows for compensatory hyperventilation

Ventilator with high FIO2

clinical pulmonary pa tho physiology

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