Pulmonary 3 Flashcards
Environmental inhales diseases
CO (carbon monoxide)
• Sulfur Oxides
• Nitrogen Oxides
• Hydrocarbons
CO2 Binds to Hb with
– No change in PaO2
200x the affinity of O2
Increases O2 affinity of remaining Hb =
does not release O2 readily to the tissues – dissociation curve shifted to the Left
CO poisoning
– Oxygen saturation % PaO2 high despite impaired oxygen deliver
CO poisoning : Dx by
measuring carboxyhemoglobin levels
– index of suspicion
Treatment of Co poisoning
No cyanosis, no tachypnea
– Tx: 100% FiO2
Nitrogen oxides –
produced when fossil fuels
burned at high temp. - yellow haze of smog, irritant
= tracheitis, bronchitis, pulmonary edema
Sulfur oxides – corrosive/poisonous – produced by
burning burning sulfur containing containing fuels @ power stations stations = chronic bronchitis, pulmonary edema
Hydrocarbons – unburned fuels in exhaust, UV light
reacts
produces photochemical oxidants (ozone,
aldehydes) greeenhouse effect – inhibit convective
processes & trap pollution at street level (LA basin)
Cigarette Smokingg
Contains 4% CO – raises carboxyhemoglobin in smoker’s blood to 10%
• Nicotine – stimulates
SNS
Nicotine excess leads to
– Tachycardia
– HTN
– Sweatin
• Tar – increase risk of
bronchial carcinoma, laryngeal, oropharyngeal, esophageal, stomach, pancreatic, cervical, kidney, bladder, ovarian, colorectal cancer, chronic bronchitis, emphysema, & CAD
Cigarette smoking Impaction
– Largest particles strike mucus surfaces, become trapped
Sedimentation with cigarette smoking
Smoke particles settle in terminal & respiratory
bronchioles, unlike gases, cannot diffuse to alveolar wall
Deposition of Particle Inhalation
Inhaled particles deposited in airways, mechanism
based on particle size
• Impaction – large particles > 5 microns filtered by
nasopharynx
Deposition of Particle Inhalation• Sedimentation Sedimentation
– particles particles 1 to 5 microns, microns, deposit deposit in terminal & respiratory bronchioles as laminar flow ceases
Deposition of Particle Inhalation
Diffusion –
particles < 0.1 micron, behave almost
like gas. Most exhaled, but some deposits in alveo
Smokers have
Centraacinar disease.
Clearance of Deposited Particles
Two mechanisms:
• Particles deposited in conducting airways cleared by
MCE (mucocilliary escalator) & swallowed
• Particles deposited in gas exchange units cleared by
alveolar macrophages (“dust cells”)
• Inhibited by: pollution, tobacco, steroids, radiation
MCE
Seromucus glands & goblet cells secrete mucus 5-10
microns thick. (Gel more viscous), Contains IgA
MCE Cilia
sweeps mucus ~ 1mm/min in bronchioles;
2cm/min in trachea. Total clearance q 24 hrs
↑contaminants =
↑ cough & mucus production and clearance
Deficient MCE predisposes to
infection & inflammatory damage – Pollution – tobacco, sulfur & nitrogen oxides paralyze cilia – Inflammation = desquamation – ↑ mucus in CB; ↑ viscosity in CF also ↓ clearance
Alveolar Macrophages
• No MCE in
alveoli
• Macrophages ingest
contaminants in alveoli
Macrophages
• Move to bronchioles to be cleared by MCE
• If ↑↑↑ particulates or toxic particles, macrophages
tend to dump ingested particles into interstitium =
Pneumoconiosis
• Diapedesis through epithelium
cleared by lymphatics
Pneumoconiosis
• Coal Miner’s Lung –
coal dust overwhelms alveolar
macrophages in terminal & respiratory bronchioles
• Condition can be simple or progressive
Coal Miner’s Lung –• Simple –
minor respiratory changes w/ series
ventilation impairments = restrictive effect
Coal Miner’s Lung –
• Progressive – Massive Fibrosis = obstructive effect
– increasing dyspnea, RF
Pneumoconiosis caused by
•
inhalation of SiO2
during quarrying, mining, or sandblasting
Coal dust vs SiO2
Coal dust is inert vs. SiO2
• Silica particles are toxic – provoke
severe fibrosis
• Silica nodules nodules form – composed of concentric
wholrs of dense collagen fibers around silica – Found in respiratory bronchioles, alveoli and along
lymphatics
Restricve effect
Asbestos –
used in insulation, brake liners & building
materials – aerodynamic, long thin fibers penetrate far
into lung
Asbestosis =
diffuse interstitial disease – Restrictive Effect
Pleural disease may occur after only trivial exposure –
Plaques may develop, usually insignificant – Malignant Mesothelioma may develop decades after
exposure
Bronchogenic Carcinoma-
originates in epithelial layer of respiratory tract
– 31% of cancer deaths in men
– 25% of cancer deaths in women (leading cause)
Other Cancers Found in Lung-
sarcoma, lymphoma, blastoma, mesothelioma, & metastases
• Smoking →
• Other exposures- radon, radiation, air pollution, iron
mining, coal mining, silica, diesel exhaust, asbestos
20 × risk for lung cancer, second hand
smoke → 30% increased risk
Symptoms of lung CA
Unproductive cough or hemoptysis common early
symptom
• Quitting smoking
decreases risk but risk never returns to baseline (non-smokers)
- 2 major categories:
- – Squamous cell – Adenocarcinoma
- Bronchioalveolar carcinoma (subtype) – Large cell
Small cell
Non-small cell lung cancers
• 2 major categories:
• Small cell (“oat cell”) – Highly malignant, rapid dissemination
•
• Small cell (“oat cell”) – Highly malignant, rapid dissemination
Non-small cell lung cancers –
Squamous cell – Adenocarcinoma
Small Cell (oat cell)
- ≈15% of lung CA
- Strongest correlation with smoking
- May secrete hormones→ paraneoplastic syndromes
Small Cell (oat cell) arises from
Arise centrally, Rapid growth, Metastasize early &
widely
Small cell prognosis
• Worst prognosis, median survival from diagnosis 1-3
months, 10% 2 year survival
Small cell have Paraneoplastic Syndromes
often the first clinical manifestation of cancer – SIADH- most common (up to 40%) – Gastrin releasing peptide – Calcitonin – ACTH → Cushing’s syndrome
Squamous Cell
≈30% of lung CA • Centrally located near hilum • Protrude into bronchi • Hemoptysis & obstructive pneumonia are common presenting symptoms • Metastasize late to hilar nodes
Anenocarcinoma
≈35-40% of lung CA
• Arise in peripheral lung- surgical resection possible
but metastasize early & widely
• Usually discovered on CXR
• Pain & dyspnea common with pleural invasion
• Bronchoalveolar cell carcinoma- slow growing,
weakest association with smoking
Large Cell
• 10-15% of lung CA • Undifferentiated (anaplastic) cells • Commonly begin peripherally but may grow to distort the trachea or bronchi • Metastasize early & widely
Bronchial Carcinoid Tumors- ≈1% of lung CA
– Arise in mainstem or segmental bronchi
– May secrete neuroendocrine hormones, carcinoid syndrome
(less likely than with GI carcinoids)
– Not related to smoking
Adenocystic Carcinoma
– Rare bronchial gland tumors
• Mesothelioma
– associated with asbestos exposure
– most are malignant
– 80% arise from pleural surface
Autosomal recessive defect on chromosome 7 →
defective chloride channel (cystic fibrosis
transmembrane conductance regulator) in sweat
glands, pulmonary epithelium, bile ducts, &
pancreas
• Viscous secreQons →
mucus plugging, defective
MCE (chronic inflammation & infections)
Cystic Fibrosis • Neutrophil dominated inflammation →
parenchymal damage (bronchiectasis) along with air trapping from plugs → bullae
Cystic Chronic infections –
S. aureus, P. aeruginosa colonize ≈75%
Cystic Fibrosis
• Sweat test- sweat chloride > 60 meq/L – (normal < 39)
Pneumonial Pathology, clinical features & treatment vary
significantly
with causative agent & pt. variables
PNA is Infection in airways→
obstruction via inflammation
(edema, SM constriction, etc) cell debris, & exudate
PNA lung damage is
• Lung damage from PMN enzymes or bacterial
virulence factors may occur
• Pleuritic pain, dyspnea, fever, malaise
• Risk factors –Pneumonia
Advanced Age - highest incidence & mortality – Immunocompromise – Smoking – Immobility – Malnutrition – Intubation – Cardiac &/or Liver disease
Pneumococcal pneumonia-organisms
→ edema, consolidaQon, infection spreads
S. pneumoniae, encapsulated organism
PNA Immune response -
IGA binds, PMNs activated,
complement system activated, cytokines released
Pneumonia Red Hepatization-
alveoli fill with blood, fibrin,
edema, & bacteria
Pneumonia Grey Hepatization-
fibrin deposits & WBCs
Staphylococcus pneumoniae
Suppurative pneumonia with abscess formation, empyema
Tuberculosis- Mycobacterium tuberculosis –
Acid fast bacillus spread by airborne particle – High incidence in HIV, drug abuse, & homeless
Bacilli tend to
• Often disseminate via lymphatics
lodge in the periphery of Apices, high
PO2 = favorable environment for bacillus
TB Can survive in
macrophages, incite more inflammation -
inflammatory cells wall off bacteria in tubercle→
caseating granulomas
TB disseminate via
• Often disseminate via lymphatics
TB Often
asymptomatic or nonspecific symptoms
Cough lasting more than 3 wks, vague flu-like symptoms,
wgt. Loss, night sweats – Multi-drug resistant strains emerging
Stages of TB:
– 1) exposure only – 2) latent infection – 3) clinically active – 4) Tuberculosis in remission – 5) Reactivation (secondary TB)
RF considered when:
– PO2 < 60mmHg = Hypoxemia
– PCO2 > 50 mmHg = Hypercapnia
Treatment of RF depends
on cause
Four mechanisms of hypoxemia:
– Hypoventilation (Weakness from NMB, narcotic OD, etc)
– Diffusion impairment (Ex. Interstitial lung disease)
– VQ mismatch (ex. Chronic bronchitis)
– Shunt
“Normal” PaO2 =Calculation
102 - 0.33 × age
Signs/Symptoms: hypoxemia
↓ PaO2 – Cyanosis – Tachycardia – Mental confusion
Tissue Hypoxia – vulnerability depends on tissue –
CNS & Myocardium most vulnerable –
•mage
Cessation of blood flow to cerebral cortex:
• 4-6 sec.
= loss of function
10-20 sec.
• 3-5 min.
= l.o.c
= irreversible damage
CNS:
– HA, Somnolence, L.O.C., Retinal hemorrhages, brain
damage
Cardiovascular:
Cardiovascular:
–1st (↑SNS)Tachycardia/HTN, 2ndBradycardia/Hypotension
– Angina/HF may occur if CAD present
– Renal impairment w/ Na+ retention & proteinuria
– Pulmonary HTN 2o to alveolar hypoxia
Hypercapnia caused by
Caused by:
• Hypoventilation
• Muscular weakness - residual NMB, myasthenia gravis,
Guillain-Barre
• Sedation - decreases hypercapnic respiratory drive
• Mechanical failure of the chest wall – Ex. flail chest
Hypercapnia
• ⇑Work of breathing
• CNS receptor desensitization, permissive
hypercapnia
• renal compensation ( for ↑ H2CO3 - )
• CNS desensitization from chronic hypercapnia →
dependency on hypoxic respiratory driv
Hypercapnia treatment with
Treatment with O2 could suppress hypoxic drive
and increase CO2 retention/acidosis
• Answer is to give low concentration (24-48% O2)
and monitor ABGs frequently to determine
whether depression of ventilation is occurring.
Diaphragm Fatigue
•
Hypercapnia impairs diaphragm contractility
• Hypoxemia accelerates onset of fatigue
Diaphragm Fatigue limited by reducing work of breathing:
– Treat bronchospams
– Control infection
– Give O2 judiciously to relieve hypoxemia
(Methylxanthines and diaphragm fatigue?
improve diaphragm contractility & relieves bronchoconstriction)
ARDS is a
Multi-organ system disease (SIRS) resulting from: – major trauma, aspiration, inhalation injury, sepsis
(especially gram negative), and shock. ≈40% mortality
ARDS Pathologic progression: – Type 1 alveolar
alveolar cells & capillary endothelium damaged =interstitial edema – Alveolar exudate & hemorrhage – ⇑Neutrophil & macrophage activity – Type 2 cells replace type 1- much thicker – Cellular infiltration in interstitium & fibrotic changes, consolidation
Capillary Pathology:
•
• endothelial damage → ⇑ permeability & exudate
• Inflammatory response- neutrophils/macrophages
cause more injury, chemotactic factors, &
Inflammatory response- neutrophils/macrophages
cause more injury, chemotactic factors, &
inflammatory mediators
Endothelial damage → platelet & complement
activation, intravascular thrombosis
ARDS
• Clinical Manifestations: –
Rapid, shallow breathing – Marked dyspnea – Restrictive & obstructive lung defects – ⇓FRC – Hypoxemia unresponsive to O2 therapy – Diffuse alveolar infiltrates on CXR & rales
Clinical Progression of ARDS
• hypoxia → hyperventilation → respiratory alkalosis
→ progressive dyspnea
• ⇑WOB → metabolic acidosis → fatigue →
respiratory acidosis & worsening hypoxia →
pulmonary HTN, cardiac decompensation & death
Infant Respiratory Distress Syndrome
• Chief cause:
↓ surfactant – Premature infant – inadequate production
• Transudate & cellular debris in alveoli
• Right-to-left shunt exaggerates exaggerates hypoxemia hypoxemia
• Hemorrhagic edema
• patchy atelectasis
• hyaline membranes
• Tx: – PEEP or CPAP frequently beneficial – exogenous surfactant via the trachea
Oxygen Therapy
• For treatment of Hypoxemia
– Recall the 4 mechanisms: hypoventilation, diffusion
impairment, VQ mismatch, Shunt
– Chart represents a hypoxic pt. breathing air, or given
FiO2 100%
• Breathing air only
= PaO2 of 50 mmHg
Oxygen Therapy
• Hypoventilation
– FiO2 100% increases PO2 > 600 mmHg
• VQ mismatch
– Most common cause of hypoxemia
– FiO2 100% effective b/c eventually washes out nitrogen
from all ventilated areas – increases alveolar PO2> 600
mmHg
Oxygen therapy • Diffusion impairment
– CO2 unaffected b/c diffuses 20x faster than O2
– Small increase of inspired oxygen of 30% raises alveolar
PO2 by 60 mmHg (remember air = 21%); PO2 > 600
mmHg
Oxygen therapy Shunt
– Refractory to O2 therapy
– Only small increase in PaO2
– FiO2 100% raises alveolar PO2 to 600 mmHg – raises
dissolved oxygen in plasma from 0.3 to 1.8 ml of O2/100
ml of blood.
⇑⇑FiO2
•
Alveolar epithelial damage → Type 2 cells replace
type 1
• Capillary endothelial damage → ⇑permeability,
interstitial edema
• Interstitial exudate → fibrosis
• Absorption Atelectasis with low V/Q ratio - ⇑PAO2
in under ventilated alveoli, O2 absorbed → alveoli
collapse = atelectasis
