Restrictive and obstructive respiratory disorders. Pneumonia.

Respiratory insuficiency

Institute of Pathophysiology

Faculty of Medicine

Comenius University

Respirator insuficiency

• Definition:▪ inability of the respiratory system to ensure adequate gas exchange

▪ result: hypoxemia, hypercapnia or both

• Basic criterion:▪ assessment of blood gases

Respiratory inuficiency

Hypoxemia +/- hypercapnia

• Normal levels of blood gases▪ PaO2 = 10 – 13,3 kPa (75 – 100 mmHg)

▪ PaCO2 = 4,8 – 6,1 kPa (36 - 46 mmHg)

• Definition▪ PaO2 < 8,0 kPa (hypoxemia) s / bez PaCO2 > 6,5 kPa (hypercapnia)

• Classification (according to blood gases levels)▪ partial (type I, hypoxemic) – hypoxemia

▪ global (type II, hypercapnic) – hypoxemia, hypercapnia + according to phvalue: compensated (normal ph value) / decompensated (↓ ph value)

• Classification

1. partial / gobal

compensated / decompensated

2. acute /chronic / chronic – acutely exacerbated

3. latent / manifest

Partial (type I, hypoxemic) Global (type II, hypercapnic)

hypoxemia hypoxemia + hypercapnia

respiratory alkalosis respiratory acidosis→ compensated /

decompensated global RI

acute cases chronic cases

V-P imbalance, intrapulmonary shunt ↓ minute ventilation / ↑ dead space

Acute RI

➢Etiology: dramatic asphyxic conditions, acute CNS poisoning, acutebronchiolitis, pulmonary inflammation, ARDS

➢CP: symptoms of basic disease + symptoms of RI: central cyanosis,convulsions, ph <7,2 = disturbances of consciousness, ph <7 = unconsciousness

➢Therapy: urgent treatment of the underlying disease, airways release, reanimation, artificial respiration, oxygen therapy, ABB treatment

Chronic RI

• pulmonary causes: ➢chronic obstrction of URT and LRT (tumors, foreign bodies), COPD (80% of cases),

pulmonary parenchymal diseases (pulmonary fibroses, pulmonary emphysema), cardiovascular diseases, chronic pleural diseases, pleural effusions

➢direct consequences of RI: pulmonary arterioles muscularization and right ventricular hypertrophy

➢complications: pulmonary hypertension, cor pulmonale

➢CP: hypoxia =fatigue, weakness, restlessness, ↑ irritability, depression, speech and vision disorders; hypercapnia = sleepiness through the day, night restless sleep and dreadful dreams, attenuation of the CNS → coma

➢physical findings: central cyanosis, ↑ neuromuscular irritation (tremor, muscleswelling), signs of hyperkinetic circulation, pulmonary hypertension and corpulmonale (warm wet skin, raised veins, swelling of the face, passivehyperaemia, increased scleral gloss), increased jugular vein filling, enlarged liver

Chronic RI

• extrapulmonary causes:▪ CNS diseases and damage (infection, trauma, vascular disorders), PNS damage

▪ myopathies, chest wall damage, kyphoscoliosis, obesity, surgical procedures

• chronic hypoxia → adaptive changes: ➢↑ of increase of 2,3-diphosphoglycerate with the shift of the hemoglobin

dissociation curve to the right, polyglobulia (↑ Htc and blood viscosity, ↑ concentration of Hb in erythrocytes)

➢↑ pressure in arteria pulmonalis→ muscularization of pulmonary arterioles, pulmonary hypertension → cor pulmonale

➢severe hypoxemia → lactic acidosis

➢hypercapnia → sequential adjustment of ph value and respiratory acidosis compensation

Chronic – acutely exacerbated RI• chronic RI + intercurrent infection / oxygen therapy / sedation / cardiac

weakness

Latent RI

Manifest RI

Summary:Etiology:

• pulmonary failure – diseases of respiratory tract, alveoli, alveolocapillary membrane or pulmonary vascular system

• extrapulmonary failure– disorders of breathing center / prolonged spnal cord / respiratorymuscles or their inervation, disorders of chest wall

Clinical picture:

• tachypnoea, dyspnoea, ortopnoea (involvement of the auxiliary respiratory muscles)

• auscultation – weakening / dysappearance of breathing sounds

• cyanosis

• anxiety, agitation, quantitative disturbance of consciousness

Investigation:

• ABB and blood gases

• history - circumstances of dyspnoea, intoxication, infections, state of consciousness

• physical findings - pulmonary sound phenomena, cyanosis

• RTG, CT

• spirometry, ECG, ECHO

Pathophysiology of RI

Oxygen-hemoglobin dissociation curve

Respiration = 4 processes: ventilation diffusion perfusion breathing control

hypoventilation diffusion disorders V-P disproportion R-L pulmonary shunt

RIcompensation of

hypoventilated alveolus -vasoconstriction

functional, anatomicaland physiologicalpulmonary shunt

DLC

Effect of hypercapnia on the organism = acidosis and its effects on the CNS

1. hypercapnia = acidification of internal enviroment → vicious cycle= deepening of hypercapnia

2. hyperkapnia = vasodilatation (hot skin, risk of edema of the brain -headache, ↑ intracranial pressure, optic nerve papillae edema, ↓ mental performance, trauma, purposeless twitch movements, lazy speech, mood swings, somnolencia to coma)

3. alveolar hypoventilation → alveolar hypercapnia + alveolar hypoxia

Effects of hypocapnia on the organism

• = alkalisation of the inner environment - ↓ degree of ionized calcium = from ↑ neuromuscular irritability to generalized convulsions

• = vasoconstriction of the cerebral vessels → symptoms of inadequate oxygen supply of the brain = headache, dizziness

The relationship of neuromuscular irritabilityand concentrations of each ions

Na+ K+ Ca2+ Mg2+ H+

Pneumonia

Defensive mechanisms of respiratory tract

• Anatomical barriers of respiratory tract▪ mucous membrane traps mucociliary apparatus removes particles / MO

cleansing is aided by coughing

• Overcoming anatomical barrier▪ in sleep – aspiration of oropharyngeal secretion

▪ change in viscosity of the secretion / in performance of the ciliary apparatus isinvolved in the removal of pathogens

• Alveoli▪ do not contain mucociliary apparatus or muciparous cells → cleaning of these

spaces by phagocytes and humoral factors in the surfactant

Pneumonia in otherwise healthy people???

→ occurs when several mechanisms are broken (anatomical barriers, cellular and humoral mechanisms in alveoli):

▪ changed consciousness

▪ impaired defensive reflexes (cough, disorder of mucociliary apparatus)

▪ bronchial obstruction

▪ impaired function of alveolar macrophages

Defensive mechanisms of respiratory tract

Proteolyticenzymes

IL-1, cachectin =

fever, chills, malaise, myalgia

AM pathogen inflammatory response

leukotriene B4, C3a a C5a, components of the kinin system

chemotactic factors for PMNL + ↑ vascular permeability

= massive supply of PMNL (infiltration)

Inflammatory response

Pneumonia

• inflammation distally from bronchioli terminales (respiratorybronchioli, alveoli, interstitium)

• transmission paths:▪ aspiration from oral cavity / nasopharynx (most often)▪ inhalation from air▪ hematogenous▪ penetration from the neighborhood

• especially children and elderly

Pathophysiology

Immediate functional consequences of inflammation:

• ↓ compliance of lung tissue

• extension of the diffusion path for the breathing gases

• R-L pulmonary shunt

→ hypoxemia, without accumulation of CO2, cyanosis, dyspnoea, ARDS, abscess, empyema, pleural effusion, organization

Classification

• according to the course▪ acute

▪ chronic (˃ 3 months)

▪ recurrent (repeatedly in the same location)

▪ migrating (infiltrates migrate)

• according to the etiology▪ infectious

▪ noninfectious = pneumonitis(aspiration, inhalation, radiation, drugs, allergy)

▪ according to the place of acquisition▪ community

▪ nosocomial

• according to X-ray imaging▪ alar, lobar, bronchopneumonia

• according to the clinical picture▪ typical

▪ atypical

Etiology: the most common are bacterial:▪ community: 90%, the agents: Str. pneumoniae, Str. pyogenes, St. aureus,

Mycoplasma pneumoniae, HI, Klebsiella pneumoniae

▪ nosocomial: acquired from 48 hours to 4 days after hospitalization, the agents: Pseudomonas aeruginosa, Klebsiella pneumoniae, E. coli, Acinetobacter

Main symptoms of pneumonia:▪ cough, fever, sputum production, chest pain and dyspnoea (tachypnoea)

Physical examination:▪ auscultation: tubular breathing

▪ percussion: silenced

▪ bronchophony: strengthened

▪ fremitus pectoralis: enhanced

Pneumococcal pneumonia

• Str. pneumoniae (pneumococcus) - the most common cause of community-acquired pneumonia

• by inhalation / aspiration

• usually – infections of the upper RT are prior

• 4 stages:1. hyperaemia / congestion: inflammation begins in alveoli, exsudate formation, hyperaemia,

pneumococcal reproduction2. red hepatization: exudate fills alveoli, accumulation of PMNL, erythrocytes enter alveoli3. gray hepatization: fibrin formation, accumulation of leucocytes, erythrocyte breakdown4. resolution: resorption of exudate

• fever, painful breathing, cough (dry, later purulent / hemoptysis), expectoration, dyspnea, tachypnoea (20-45 / min), high temperature (38.5-40.5 °C), takychardia(100-140 / min)

• bacteraemia, possible extrapulmonary infections

• Haemophilus influenzae▪ 2nd most frequent agent

▪ the most virulent are the Hib strains, pleural exudate occurs in half of the patients

• Staphylococcal pneumonia▪ nosocomial pneumonia; infants, elderly people, addicts (using i.v. drugs)

▪ CP as in pneumococcal, fever

• Pneumonia caused by Klebsiella and other G- bacteria▪ most often in the weakened persons, the elderly and infants, nosocomial

• Peudomonas aeruginosa▪ severe nosocomial pathogen, acute toxic disease, abscesses, pleural effusion /

empyema, ARDS and septic shock

Atypical pneumonia• Mycoplasma pneumoniae

▪ in children, M. pneumoniae adheres to a ciliated epithelium, which isdestroyed → interstitial pneumonia, bronchitis and bronchiolitis

▪ leukocyte infiltration of peribronchial spaces, the disease is similar to flu, progression → mucopurulent sputum

▪ mild course, but if severe: hemolytic anemia, polyarthritis, thromboemboliccomplications, meningoencephalitis, peripheral neuropathy and cerebralataxia

• Chlamydia pneumoniae▪ pharyngitis, bronchitis, pneumonitis, CP as with mycoplasma

• Viral pneumonia▪ viruses into bronchiolar epithelium → bronchiolitis, infection into interstitium

→ image of pneumonia, alveoli contain fibrin, mononuclear leukocytes and neutrophils, possible formation of hyaline membranes

Typickal vs. atypical pneumonia

• S. pneumoniae, H. infuenzae

• sudden beginning

• high fever

• productive cough

• phys. finding: characteristic

• lab. finding: FW, leukocytosis

• RTG: unilateral, lobar

• Mycoplasma, Chlamydia

• sequential beginning

• subfebrile temperature

• dry cough

• phys. finding: insipid

• lab. finding: FW, leukocytosis

• RTG: bilateral, diffuse

• Mycotic pneumonia▪ most often as a complication of AIDS (Pneumocystis carinii)

▪ CP: fever, dyspnoea, dry non-productive cough, RTG bilateral perihilousinfiltrates

▪ primary: obligatory pathogenic (histoplasmosis, blastomycosis) – disease also in immunocompetent patients

▪ secondary: opportunistic pathogenic - saprophytic fungi (candidiasis, aspergillosis, cryptococcosis, nokardiosis) - opportunistic infections in immunocompromised

• Parasitic▪ protozoa: amoeba, toxoplasma

▪ helminths: echinococcus, ascaris, toxocara

Mycotic and parasitic pneumonia

Noninfectious pneumonia• Aspiration pneumonia

• most often – aspirating of stomach content• CP: dyspnoea, tachypnoea, tachycardia, cyanosis, bronchospasm, fever, coughing up

of pink sputum, ARDS, RTG - diffuse infiltration, pulmonary edema, most commonlyin the lower right lobe

• Inhalation pneumonia• irritant gases (thermal and toxic damage)• SO2, NO2, O3, chlorine, ammonia, phosgene, formaldehyde, CO2, CO, radon, asbestos

• Radiation pneumonitis• acute pneumonitis 2-3 months after actinoterapia – may be influenced by corticoids,

after 6 months - pulmonary fibrosis - steroids without effect

• Hypersensitive pneumonia see slide n. 79• exogenous allergic alveolitis (type III allergic reaction)• etiology: multiple Ag, can be a professional illness

• Pulmonary eosinophilia• eosinophilic pulmonary infiltrates and blood eosinophilia, probably as an allergic

reaction to a parasitic disease

Complications of pneumonia

Pulmonary abscess

• in the destroyed part of the lungs - pus with necrotic tissue wrapped in the (so called) pyogenic membrane

• CP: chest pain with fever, occasional hemoptoea and dyspnoea, productive cough, rotting odor of sputum and breath, intermittentfever, weight loss, anorexia

Revision

• What is the physiological immune system in the respiratory tract?

• How can be pneumonia classificased?

• What are the most common pneumonia causing pathogens?

• What is the atypical pneumonia?

• What is the noninfectious pneumonia?

Spirometry

The measured parameters are divided into:

• static - alveolar space size → inform about possible restriction disorders

• dynamic – record of airflow in RT → inform about possibleobstruction disorders

Static volumes• Vt – breath volume• IRV – inspiratory reserve volume• ERV – exspiratory reserve volume• VC – vital capacity• TLC – total lung capacity• FRC – functional residual capacity

Dynamic volumes• FEV1 - forced expiratory volume in the first second • PEF – peak exspiratory flow• MV – minute ventilation• Tiffeneau index (FEV1 / VC)

Spirometry can not measure:• RV – residual volume• Vd – dead volume

Restrictive and obstructive respiratory disorders

• Obstructive diseases➢obstruction in RT→ limited airflow

• Restrictive diseases➢↓ pulmonary compliance → ↓ TLC

Obstructive diseases

• chronic bronchitis

• emphysema

• bronchiectasis

• asthma

Restrictive diseases

• affection of the chest wall beside normal lungs

• acute / chronic interstitial lung diseases

VC: normal / slightly ↓FEV1: markedly ↓↓

↓ ratio FEV1/VC

VC: ↓FEV1: normal / proport. ↓

normal ratio FEV1/VC

COPD

Tiffeneauindex

Obstructive respiratorydisorders

COPD (Chronic obstructive pulmonary disease)• group of respiratory diseases, common sign -

parmanent ↓ FEV1 + smoking is RF• cause - ↑ resistance of RT, ↓ elasticity of lung parenchyma

• constriction of RT: caused by chronic inflammation - typical for chron. bronchitis▪ muciparous glands hypertrophy, mucus hypersecretion, change of epithelial lining to

multilayer (metaplasia of cylindrical epithelium), edema and alternativelyperibronchial fibrosis, collapse when their walls are damaged

• ↓ elasticity of lung tissue: due to loss of elastic component of its connective tissue - typical for emphysema

chronic bronchitis and emphysema – forms of COPD

COPD

Examination of breathing functions - stages of COPD:▪ stage I – light, FEV1/FVC ˂ 70%, FEV1 je 80%▪ stage II – intermediate, FEV1 50-79%▪ stage III – severe, FEV1 30-49%▪ stage IV – very severe, FEV1 ˂30% / present is RI or cor pulmonale

X-ray examination:

• emphysema, depression of the diaphragm, enlargement of retrosternal space

Physical examination:

• wheezing, dyspnoea, prolonged exspirium, signs of hypoxia

Complication of COPD – COR PULMONALE

Alveolar hypoxia vasoconstriction of pulmonary arterioles + their structuralmodification pulmonary HT COR PULMONALE

Chronic ↑ work of respiratory muscles alveolar hypoventilation globalRI (hypercapnia + respiratory acidosis) limited physical activity

Cyanosis, total edema

CP - 2 types:

COPD

Chronic bronchitis

• Def: mucus hypersecretion with chronic cough lasting at least 3 months in a year in two following years

• Etiopathogenesis:▪ smoking cigarettes▪ chronic bronchial inflammation with acute exacerbations▪ inflammation → accumulation of inflammatory cells → the source of proteolytic

enzymes (elastase, gelatinase, collagenase) - damaging RT and surroundingparenchyma

▪ → loss of epithelial ribs of affected bronchi and bronchioli, hyperplasia of glands, Goblet‘s cells and mucus hypersecretion

• chronic inflammation + structural changes of parenchyma = ventilation-perfusion imbalance → arterial hypoxemia, cyanosis, pulmonary HT

• functional abnormalities: ↑ RV, ↓ FEV1, ABB disorders

• Etiology (RF):▪ exogenous (tobacco, professional influences - dust, chemicals, polluted air,

repeated respiratory infections - HI, pneumococcus)

▪ endogenous (RT hyperactivity - asthma, genetic factors - α1-antitrypsindeficiency, hypo- / dysagamaglobulinemia)

• CP: ▪ main symptom - dyspnoea, productive cough, advanced stage - weight loss

Chronic bronchitis

• Physical examination▪ orthopnea, pouting the lips in the exspiration

▪ percussion - signs of emphysema (hyperresonant percussion), depressedposition and movement of the diaphragm

▪ auscultation - prolonged exspirium, dry rales (whistling, rasping)

• Complications:• pneumothorax, ↑ pulmonary embolism risk (physical inactivity and cor

pulmonale)

Chronic bronchitis

• change of lung parenchyma- loss of partof alveolar walls inside pulmonary acini

alveolar ducts and alveoli merge intolarger air formations that are no longersupplied by pulmonary capillaries (whichdisappear with septa)

• pathological-anatomical def.➢irreversible, progressing destruction of RT

distal to terminal bronchioles➢result of alveolar and bronchial septal

damage – formation of cysts filled with air(greater than 1 cm) = bulls (bullousemphysema)

Emphysema

Emphysema

• types:▪ panacinar - congenital α1-antitrypsin defect

▪ centrolobular (cantroacinar) type - smoking

▪ distal acinar type

• manifest by dyspnoea, progressive irreversible expiratory obstruction, arterial hypoxemia and hypercapnia of varying degrees

Emphysema - pathophysiology

• 1. loss of pulmonary acinus septa

elastase, oxygenradicals, matrixmetalloproteinase

↓ diffuse lung capacity

• 2. loss of elastic fibers

↓ elasticity of pulmonary parenchyma

ventilation is ineffective in the exchanging of blood gases ventilation > perfusion

α1-antitrypsin

Functional consequences of emphysema• mechanics of pulmonary ventilation is more affected during the expiration

• ventilation is shifted to area of IRV, because FRC and RV are increasing

• ventilation in area of IRV needs more extensive pressure changes for realisation of insipration = ↑ work of respiratory muscles during the inspiration

• ↑ resistance of airways during the expiration because of premature narrowing / closing of bronchioles

• loss of septa = ↓ total diffuse lung capacity

• FRC, RV, TLC ↑

• barrel-chest, prolonged expiration + pouting the lips in the expiration

• more moderate hypoxaemia then in CHB → also less frequent cyanosis, hypercapnia

• pulmonary HT – less singnificant then in CHB

• CHB and pulmonary emphysema occurs very common together in patients– both are caused by smoking

• 10-15% of smokers has some form of COPD

• COPD affects ˃ 10% of adult population of USA• COPD is 4th leading cause of death in USA

Chronic bronchitis

Emphysema

Cystic Fibrosis• monogenic disease, disorder of respiratory, digestive, urogenital system and skin

• mutation of the gene for protein CFTR – canal for anion Cl-

• disorder of the transport Na+ and Cl- (their ↑ resorption) → accompanied by ↑ resorption of water = secretions in airways are denser, more viscous

• cough, accumulation of secretion = failed natural purification capacity of airways→ frequent infection → chronic infection with periods of remission and exacerbation

• frequent infectious agents – Staphylococcus aureus, Pseudomonas aeruginosa

• damaged little bronchioles = ↑ expiratory resistance = ↑ RV and RV/TLC, ↓ FEV1= signs, which allocate CF into group of obstructive pulmonary diseases

• CF gradually results in chronic RI

Asthma bronchiale

• chronic inflammatory disease of airways

• AB is characterised by reversible bronchoconstrition with expiratorydyspnoea, with cough and loud breathing with wheezing

• prevalence in Europe - 5 %, in 63 % occurs before 5th year of age

Basic characterisctics of AB:• inflammatory process of the walls of airways

• hyperreactivity of airways

• obstruction of airways▪ at the beginning reversible, gradually becomes permanent▪ bronchoconstriction + edema of mucous membrane + hypersecretion of viscous mucus +

hypertrophy of smooth muscle cells

• T-lymphocytes + allergen → cytokines → production of IgE by B-lymphocytes → sensibilization of mast cells

• allergen reexposure → mast cells release mediators symptoms of athma

• repeated contact with allergen → anaphylactic reaction

• anaphylaxis▪ reaction of early type of hypersensitivity

▪ by the binding of allergen to IgE, that are bound to receptors on the surface ofmast cells and basophils → release mediators of anaphylaxis, histamin

▪ phase of sensibilization

▪ phase of activacion – very fast, in patients with atopy even faster

2 phases of anaphylactic reaction

• early asthmatic response = EAR➢within minutes, mediators are released from the mast cells→

bronchospazmus➢main mediator: histamin, leukotrienes LTC4, LTD4, LTE4, prostaglandin D2 a PAF

• late asthmatic response = LAR➢few hours after EAR, lasts several hours / days➢symptoms – much more significant➢inflammatory cells, eosinophils, basophils and T-lymphocytes, macrophages,

epithelial cells produce substances → maintenance and promotion of inflammation with bronchoconstriction, ↑ capillary permeability, vascular congestion and edema formation, mucus production and impaired mucociliary transport

➢chemotactic substances – arrival of eosinophils, thrombocytes and PMNL to the place of mast cells stimulation

• Functional consequences of asthmatic attack:▪ ↑ work of respiratory muscles, dyspnoea, ↑ RV and FRC (inspiratory position

of the chest and breathing in area of IRV), arterial hypoxemia

▪ classic asthmatic attack – only a slight hypercapnia

▪ during the asthmatic attack ↓ FEV1, PEF, can be ↑ FRC, RV, TLC, ↓ STK during the inspiration and ↓ pulse wave size (pulsus paradoxsus)

▪ mucus plugs

• Severe asthma attack (status asthmaticus)▪ generalized bronchoconstriction - long-term, insufficient response to classical

treatment, causes global RI

▪ life-threatening condition

Clinical symptomatology

• always constant triad: dyspnoea, cough, wheezing

• seizures often at night

• during seizure – prolonged exspirium, tachypnoea, tachycardia, hypoxia, hypocapnia, respiratory alkalosis, unproductive cough

• Retained air in the lungs → ↑ intrathoracic pressure → difficult breathing, patient is restless, cyanosis (in laterstages), ↑ jugular vein filling

• retention of CO2, tachycardia and tachypnoea are predictive hypercapnia = significant obstruction

• end of seizure – coughing up of fibrous sputum (Curschmann spirals, eosinophils, Charcot-Leyden crystals)

• If cough is ineffective – mucus obstructs bronchiols → atelectasis

• rare complication – spontaneous pneumothorax

• genetic factors➢atopy

➢family history

• environmental factors➢allergens

➢infections (mainly viral)

➢professional expositions

➢smoking

➢air pollution

• trigger factors: ➢GER (especially during sleeping),

infections of airways, environmentaland dietary problems (allergens), stressful state

➢physical stress, hyperosmolarity

Etiology + triggers

Types of asthma

Extrinsic (atopic, allergic) asthma:

oparticipation of the immune system

o cause: type I hypersensitivity reaction, trigger is a substance from the

environment (evidence of allergen)

o↑IgE in serum

Intrinsic (nonallergic) asthma:

o greater importance is attributed to VNS

o cause: trigger is emotional stress, cold, dry air, physical stress, aspirin, viral infection (lack of evidence of allergen)

onormal IgE in serum

Classification of asthma according to the severity of the manifestations, degree of airway obstruction and its variability

1. intermittent▪ seizures: maximum once a week, nightly maximum twice a month▪ between seizures: normal functions, PEF <20%, without limitation of physical activity

2. persistent light▪ several times a week▪ PEF 20-30%, spirometry at rest> 80%, sleep disturbance and disturbance of daily activities

3. persistent medium▪ daily seizures▪ PEF> 30%, spirometry values at rest 60-80%

4. persistent severe asthma▪ persistent symptoms, significant activity limitation, nocturnal difficulties▪ PEF often undetectable, spirometry values at rest <60% (state of permanent obstruction)

Bronchiectasis

• irreversible anatomical dilation of one or more bronchi

• cause: chronic inflammation process → destruction of the elastic -muscular wall of the bronchus

• before the era of ATB - they were incurable diseases

• Etiology + dividing:• disorders of the mucociliary

apparatus (primary ciliarydyskinesia = Kartagener syndrome)

• cystic fibrosis

• immunodeficiency states(agammaglobulinaemia)

predispositions to infection

• infections with bronchial wall destruction

• long lasting coughing

• after necrotizing pneumonia, aspergillosis

• post-stenotic form of bronchiectasis

• cirrhotic form (fibrosing TB, diffusepumonary fibrosis, sarcoidosis)

congenital bronchiectasis obtained bronchiectasis

• Etiopathogenesis:• beginning - an infectious / chemical pathogen is always present →

subsequent development of inflammation

• disability of bronchi in the middle part of the tracheobronchial tree→peripheral parts are badly ventilated

• Radiologically - 3 types according to shape:▪ cylindric▪ varicose (fuziform, spindle)▪ saccular / cystic

• saccular - a cavity filled with pus, it reaches the periphery of the lungs

Clinical picture

• 90% of patients - ↑ expectoration in the morning after waking up

• 50% of patients - hemoptoe

• disorder of respiratory functions - depending on the anatomical type and range

• in advanced stages - dyspnoea, in extensive stages - hypoxemia without hypercapnia

• complications - pulmonary hypertension and cor pulmonale

• diagnosis is confirmed by X-ray of tracheobronchial tree, bronchography, CT

• cultivation of sputum → targeted ATB treatment

Restrictive respiratory disorders

• heterogenous group of disorders

• chronic bilateral involvement of connective tissue – of alveolar wallinterstitium

• Etiology? Pathogenesis?

• Similarities!▪ signs, symptoms, radiological alterations, pathophysiological changes

▪ ↓ compliance of the lung tissue → ↑ work of respiratory muscles + dyspnoea

▪ V-P → hypoxia (RI) → pulmonary HT, cor pulmonale

▪ X-ray: small knots, irregular lines, “cut glass“ shades

• idiopathic pulmonary fibrosis

• sarcoidosis

• lung fibrosis in systemic diseases

• interstitial lung diseases caused by dust inhalation

• hypersensitivity pneumonitis

• drug and radiation-induced lung diseases

Fibrotizing diseases

known cause

unknown cause

Fibrotizing diseases

• ↑ fibrosis in the lung parenchyma = ↓ compliance against pressurechanges = ↑ work of respiratory muscles

• the cause of fibrotic process – interstitial chronic inflammation and alveolitis• known causes of inflammation (pneumoconiosis, hypersensitivity pneumonitis, irradiation of

lungs by ionizing radiation, acute lung damage by smoke and toxic gases, aspiration pneumonia, ARDS)

• idiopathic lung fibrosis, sarcoidosis

• 1. clinical manifestation – exertional (later even resting) dyspnoea, crepitations, fisrtly latent RI (later manifest, in final stages even type II)

• typical restriction disease = ↓ TLC, VC, FEV1, RV, at normal FEV1/FVC, ↓ diffusioncapacity by more than 30%

Idiopathic pulmonary fibrosis

= diffuse interstitial lung fibrosis

• etiology: unknown

• ↑ content of fibrotic tissue in the pulmonary parenchyma → ↓compliance with pressure changes

• consequence: severe hypoxia + cyanosis

• CP: non-productive cough + progressive dyspnoea, later - cor pulmonale

• Prognosis: 2-4 years despite of intensive treatment

Pathogenesis

• unknown Ag → stimulates T-ly → cytokines

• CIC → macrophages activation of macrophages

IL, leukotrienes TGFβ + PDGF

PMNL→ proteases mesenchymal cell proliferation

destruction of the alveolar epithelium interstitial fibrosis

and interstitium

Sarcoidosis

Def: • multisystemic disease

• non-necrotizing granulomas (giant multinucleated cells, macrophages, epithelial cells, T-ly, B-ly, plasmatic cells, PMNL, fibroblasts, collagen, Ig and C3 component of complement)

Cause: unknown

• depends on the location of the granulomas▪ lungs (80%), skin, LU, brain, eye, myocardium, reticuloendothelial system, muscles and joints▪ granulomas degrade, penetrate, compress and distort tissues

• clinical triage in children: arthritis, uveitis, dermatitis

• initial symptoms: anorexia, weight loss, lethargy, weakness, malaise, fever, nausea, headache, dry cough, dyspnoea, chest pain, tachypnoea and wheezing

• alveolitis and fibrosis (x-ray image - honeycomb) → cor pulmonale

• extracorporal manifestation:• hepatosplenomegaly, lymphadenopathy, maculopapular lesions of the skin, affection of eye

(even amaurosis), lacrimal and salivary glands, cardiac arrhythmias, cardiomyopathy, myocarditis, pericardial effusions, nervous affection of system (image of aseptic meningitis, encephalitis, peripheral neuritis), muscles, endocrine glands, bones, kidney disease (urethralobstruction / glomerulonephritis)

▪ Löfgren sy. – erythema nodosum, hilar adenopathy, iritis, arthropathy and fever▪ Mikulicz sy. – ccular disorder with bilateral edema of lacrimal and salivary glands▪ Sjögren sy. – keratoconjunctivitis with enlarged glandula parotis and lacrimal glands

Sarcoidosis - CP

sarcoidosisvariants / imitatesarcoidosis

Sarcoidosis

Prognosis:

• 50-60% spontaneous remission

• 30-50% cured after corticotherapy

• 10-20% disease persists – chronic fatigue, chronic RI, progressive dyspnoea

• 2-5% mortality

Lung fibrosis in systemic diseases

• rheumatoid arthritis - changes in the lungs in 25% of patients, possibly due to RA therapy (methotrexate)

• SLE – CIK deposition into alveolar wall → alveolitis

• Goodpasture syndrome• pulmonary haemorrhage, glomerulonephritis• Ig against alveolar BM and BM glomeruli

• idiopathic pulmonary hemosiderosis - alveolar haemorrhage, sideropenicanemia, lung infiltration

Interstitial lung diseases caused by dust inhalation

Inhalation of inorganic dusts = Pneumoconiosis

▪ parcitles of inorganic dust damage the lung parenchyma → inflammatoryresponse → disappearance of the alveolocapillary unit

Inhalation of organic dusts▪ image of hypersensitivity pneumonitis (extrinsic allergic alveolitis) occurs,

after repeating of episodes, an image of interstitial lung disease may develop

Anorganic dust

• asbestosiso pulmonary fibrosis, more frequent malignities RT

and pleura

o after 10 year exposure to asbestos dust

o macrophages phagocyt particles → macrophagemembrane disruption → lysosomal enzymes → lung parenchyma damage → fibrotizing changes = acinar obliteration = typical bee honeycomb image

o 80% of mesotheliomas are related to asbestosis

• silicosiso SiO2 particles (in quartz processing)

o after 10 months of exposure, it may be fatal at <2 years

• anthracosiso carbon behaves inertly (does not cause

fibroproduction but pigmentation – soot), in miners after 20 years of exposure

o coal dust + smoking = very adverse

• anthracosilicosiso Carbon particles and crystalline SiO2 in the inhaled

aerosol

o ↓↓ diffuse lung capacity, premature mortality

o Caplan sy. – miners in coal mines, seropositive rheumatoid arthritis + progressive fibrosis of the lungs

• beryliosiso acute pneumonitis / chronic interstitial

pneumonitis

o biopsy - granulomatous formations

Organic dust

• is the cause of hypersensitivity pneumonitis (exogenic allergicalveolitis)

• it participates in the pathogenesis of asthma

• farmer's lungs▪ usually an acute condition, begins after a 4-8-hour exposure

▪ CP: fever, cough, dyspnoea without wheezing

▪ form of hypersensitivity pneumonitis, workers in agriculture – plants withoccurrence of thermophilic actinomycetes (in steamy hay)