Disorders of the Respiratory System

Site of gas exchange

Capillaries

What type of conditions cause decreased gas exchange?

Conditions that thicken the membrance seperating the alveolus and capillary

Type I pneumocytes

95% of alveolar epithelium

Provides structure

Easily damaged

Type II pneumocytes

Secrete surfactant which keeps alveoli from collapsing (atelectasis)

Repairs epithelium by producing type I pneumocytes

alveolar macrophages

Phagocytic cells of the innate immunity

PaO2 (> 80 mmHg)

Partial pressure of oxygen

Amount of pressure oxygen exerts in the blood vessels

Measured by arterial blood gas

Increased pao2 means

More O2 is forced to bind to hemoglobin

SaO2

Oxygen saturation

Measured by pulse ox

% of hemoglobin that is bound to O2

Decreased PaO2 leads to

Decreased SaO2

What is the most common cause of hypoxemia?

V/Q mismatch

No ventilation or perfusion to the alveoli

Diffusion of O2 from alveoli to blood is dependent on..

Ventilation and perfusion

FEV1

Forced expiratory volume in 1 sec after full inspiration

FVC

Forced vital capacity

After full inspiration, total amount of air that you can blow out until you can't anymore

what FEV1/FVC ratio is indicative of obstructive lung disease?

< 0.7

Common cold etiology

Rhinovirus (most common)

Respiratory syncitical virus

Coronavirus

Parainfluenza

How is common cold spread?

Direct contact

Less common by aerosol

Symptoms of common cold

Dryness and stuffiness of nose

Clear runny nasal secretions follows

Swollen nasal membranes

Post nasal drip—> sore throat

Rhinosinusitis

Upper respiratory infection(usually viral)

Mucosal swelling impedes flow out of sinuses

What normally causes chronic rhinosinusitis?

Bacterial or fungal infection

can last over 12 weeks bc the bacteria continue to grow in the moist environment

Symptoms of rhinosinusitis

Headaches

Face pain

Purulent nasal discharge

Fever

Croup

Upper respiratory infection common in children

Can be caused by virus, bacteria, associated with GERD,etc

Laryngotracheitis (croup)

Viral upper airway infection leading to inflammation from the vocal cord to bronchi

Symptoms of croup

Inspiratory Stridor

Bark seal like cough

Hoarse voice

Sore throat and low grade fever

Pathophysiology of croup

Infection —> inflammation —> accumulation of fluid in subglottic space which obstructs the airway

Epiglottitis

Potentially fatal inflammation of the epiglottis and pharynx

Etiology of epiglottitis

Due to bacterial infection

S.aureus, S. Pneumonia, S. pyogenes

Symptoms of epiglottitis(AIR RAID)

Airway inflammation/obstruction

Inspiratory stridor

Restlessness, lethargy

Retractions, nasal flares

Anxiety

Increased pulse

Drooling

Pale

Mouth open and chin tucked out

What immediate action must be taken when an individual is assumed to have epiglottitis?

Clear airway immediately

Influenza

Viral respiratory infection

More contagious than bacterial infection

Incubation period for influenza

1-4 days

Can be contagious one day before symptoms begin

Hemagglutinin

Subtype of Infulanza A

Allows virus to attach to respiratory epithelial cells

Neuraminidase

Subtype of Influenza A

Helps newly formed virus release from respiratory epithelium

Pathophysiology of influenza

Attaches to respiratory epithelium

Enters the epithelium to replicate

Replication destroys epithelial cells and also exposes basal cells

Fluids and cytokines leak out

Inflammation occurs (redness, swelling of respiratory tract)

Extracellular fluid escapes through holes (runny nose)

How can influenza lead to further infection?

Ciliated cells, and other epithelial cells are damaged

Mucous secretion and ciliary action is decreased

Exposure of basal cells allows bacteria to enter

Symptoms of influenza

Nasal discharge

Muscle aches

Abrupt onset of fever and chills

Non productive cough

Sore throat

Rapid onset of malaise

Secondary complications of influenza

Bacterial pneumonia

Viral pneumonia

Croup

Pneumonia

Inflammation of LOWER respiratory tract

Caused by infectious agents and non infectious agents (toxins, hot air,etc)

risk factors of pneumonia

Age

Smoking

COPD

Immunosuppressed

Endotracheal tube

Unaltered consciousness

Lobar pattern of distribution of pneumonia

Consolidation of one lobe

Bronchopneumonia pattern of distribution

Patchy distribution

Community acquired pneumonia

Acquired outside of the hospital or within 48 hrs of admission

S. pneumonia

Legionella

Influenza

Hospital acquired pneumonia

Acquired 48 hours after admission

Most have antibiotic resistance

Klebsiella pneumonia

Pseudomonas aeruginosa

acute bacterial pneumonia

Aspiration of secretions from oropharynx is most common

Legionella(inhalation)

Endotracheal tubes

clinical manifestations of pneumonia

Cough

Dyspnea

Fever

Crackles

Signs of consolidation (tactile fremitus, egophony, whispered pectroliloquy)

What is the model bacterial pneumonia?

Pneumonococcal pneumonia

Pneumonococcal pneumonia

Aspiration of streptococcus pneumonia

Alveolar macrophages ingest the bacteria and release cytokine which induce inflammation

Stage 1: Congestion

Alveoli and interstitial fluid fill with protein rich fluid (edema)

Bacteria not ingested by macrophages grow in edema and spreads to adjacent nodes

Stage 2: Red hepatization

RBCs , neutrophils and fibrin accumulate in alveoli and interstitial fluid—> consolidation

Stage 3: grey hepatization

RBCs dissipate

Neutrophils and macrophages are still fighting for their life!

Stage 4: Resolution

Enzymes or macrophages remove fluid and debris

Viral pneumonia

Common cause: influenza

Milder and self limiting but can set the stage for bacterial infection

Damages epithelial cells and goblet cells

Bronchial wall gets sloughed off and bacteria can attach causing edema and leukocyte infiltration

Difference between pneumococcal pneumonia and viral pneumonia

Viral pneumonia cannot be seen on x ray because there is no fluid accumulation or consolidation!

Tuberculosis (TB)

Caused by mycobacterium tuberculosis (acid fast) which has a waxy capsule to protects itself from immune system

Risk factors of tuberculosis

Spread by respiratory air droplets(coughing, sneezing)

VERY Contagious

Crowded living environment

People with substance use disorder

People w/o fixed residence

Lack of screening

Primary Tuberculosis

1. Bacteria enter the airways & lands into alveoli (upper airways)

2. Alveolars macrophages eat them up

3. Bacilli replicate within macrophage

In intact immune system macrophages exit alveoli and enter interstitial tissue and initiate cell mediated immunity

Cell mediated immunity tuberculosis

After first 3 weeks

1. Infected macrophages attach TB antigen to MHCII—> CD4—>T helper cells

2. T helper cells recruit more macrophages and lymphocytes

Formation of granuloma (tubercle) to isolate mycobacterium

3. Center of granuloma can become necrotic(caseous necrosis) called a Ghon focus)

4. Ghon focus might spread to regional lymph node (Ghon complex)

-may create caseation in hilum, fibrosis, calcification

In tuberculosis, when a person is in the latent stage, are they still contagious?

No the bacteria is dormant

In some patients w/ tuberculosis how do T helper cells help to destroy bacteria?

T helper cells will modify macrophages and destroy the bacteria

Macrophages produce more enzymes/nitric oxide to destroy bacillus

T helper cells that will destroy infected macrophages.

What does bacterial pneumonia resemble?

Primary tuberculosis

Secondary Tuberculosis

Previously sensitized host

Occurs secondary to exposure or reactivation of latent TB

Infection spreads to upper lobe

Immune response is rapid

Pathophysiology of secondary tuberculosis

Multiple areas of caseous necrosis (more granulomas)

Lesion can erode into airways—> expel contents into airways—>formation of a cavity (cavitation)—> bronchopneumonia

Miliary TB can develop (kidneys, menignges, liver, etc)

Person is infectious when bacillus gains access to sputum

Symptoms of secondary tuberculosis symptoms:

Hemoptysis

Night sweats

Anorexia

Fatigue

Low grade fever

Pleuritic pain

Lung Cancer risk factors

Smoking

Genetics

Occasional exposure to certain(asbestos fibers, diesel, fuel, radon gas, silica, etc)

Small cell lung cancer

Most commonly caused by smoking

Most aggressive

Location: bronchi to periphery

Rate of growth: Rapid

Metastasis: spreads wide and quickly

Squamous cell carcinoma (non small cell)

Risk factors: smoking, COPD

Location: perihilar -may project into bronchi

Rate of growth: slow

Metastatic: late course of disease (usually to hilar lymph nodes)

Adenocarcinoma( non small cell)

Occurs in nonsmokers

Location: peripheral of pulmonary tissue around alveoli

rate of growth: moderate

metastatic: early to lymph node,pleura, bone, brain

Risk factors: exposure to occupational carcinogens, tobacco smoke, viruses, hormones, and family history increase risk

Large cell carcinoma

Least common

Undifferentiated

Risk factors: same as adenocarcinoma

Metastasis: early and widespread

Location: can be anywhere

Rate of growth: rapid

Clinical manifestations of lung cancer

Anorexia, weight loss

Hemoptysis, cough, wheezing, SOB

Hoarseness

Difficulty swallowing

Paraneoplastic syndrome

Parathyroid hormone related protein leads to what paraneoplastic syndrome?

Hypercalcemia b/c excess calcium is pulled out of the bone and is now in the blood.

Respiratory Distress syndrome

Common cause of respiratory disease in premature infants

Pathophysiology of respiratory Distress Syndrome

immature type II pneumocytes cannot synthesize surfactant which causes alveoli to collapse between breaths

Increased work of breathing

Clinical manifestations of respiratory distress syndrome

Respiratory distress

Inspiratory retractions

Cyanosis

Grunting w/ expiration

Pleural effusion fluids

Transudate: translucent , no cells or protein

Exudate: leukocytes and protein

How to treat pleural effusion?

Usually self resolves but can be treated with thoracentesis

primary(spontaneous) pneumothorax

Common in men 20-40 years

Risk from smoking

Rupture of a blister(bleb) on the visceral pleura

Allows for air from the alveoli to enter the pleura

Secondary (traumatic) pneumothorax

Due to chest trauma

COPD, needle aspiration

Open pneumothorax

Air can freely move in(inspiration)/ out during expiration

Tension pneumothorax

Wound acts as a one way valve

Air comes in during inspiration/cannot escape during expiration

Increased air pressure within pleura

Compression of mediastinum, heart, great vessels and trachea

Increased pressure can prevent blood from going into right atrium

tension pneumothorax symptoms

Tracheal deviation

Tachycardia

Dyspnea

JVD

Low BP

Pneumothorax symptoms

Absent breath sounds

tachypnea

Dyspnea

Pleural pain

Hyperresonance

Atelectasis

Collapse of lung tissue

Compression on lungs by tumor , fluid, etc

Absorption of air from obstructed alveoli

Poor production of surfactant

Risk factors and Symptoms of atelectasis

Factors: surgery, shallow breathing, pain, immobility

Signs: Dyspnea, cough, fever

Obstructive pulmonary diseases

Airway obstruction that is worse during expiration

Prolonged expiration

Symptoms of dyspnea and wheezing

Increased work of breathing

Extrinsic (atopic)asthma

IgE mediated eosinophilic allergic reaction

Bronchial mucosa is exposed to antigen

T helper —-> IgE antibodies which coat mast cells

Recruitment and activation of eosinophils

Increased mucous production from goblet cells

Acute phase response of extrinsic asthma (30 min)

Antigens bind to IgE on pre sensitized mast cells

Mast cells degranulate and release histamine

Increased capillary permeability, vasodilation, mucosal edema

Bronchospasm

Mucous production

Recruitment and activation of eosinophils

Late response of extrinsic asthma (4-8 hrs)

Increased bronchial hyper responsiveness

Vasodilation, capillary permeability, bronchoconstriction, mucous production

Eosinophils infiltrate the tissue and release granules which leads to epithelial damage

Symptoms of asthma(only during attack)

Chest tightness

Tachycardia

Non productive cough

Prolonged expiration

Dyspnea, exploratory wheeze, tachypnea

What happens when bronchospasm does not resolve after trying to treat with usual measures? (Antihistamines, bronchodilators, etc)

Status asthmaticus (hypoxemia and respiratory acidosis)

Intrinsic asthma

Exercise induced and Aspirin/NSAID induced

What causes intrinsic asthma due to NSAID/Aspirin use?

Excessive use can lead to the development of asthma, nasal polyp and rhino sinusitis due to abnormal metabolism of arachnoid acid which increases pro-inflammatory cytokines

Emphysema symptoms

Irreversible enlargement of air spaces distal to terminal bronchiole

Pink puffers

No cyanosis

Increased WOB—> accessory muscles

Dyspnea on exertion,

pursed lips, expiratory wheezing, prolonged expiration

Barrel chest

Hyperresonance

Emphysema due to tobacco smoking..

Smoking releases ROS that damages epithelium

Release of neutrophils which secrete elactase

Elactase breakdown elastin—> loss of recoil and increased lung complaince'

Emphysema due to genetic deficiency of a1-antitrypsin

genetic defect keeps elactase from being neutralized

Tissue destruction occurs

Can occur in nonsmokers

What is an emphysema patients stimulus to breathe and why is this important for treatment?

Stimulus is low O2

This is important bc you cannot give them over 60mmHg of oxygen for treatment because it can cause hypoventilation and co2 retention

Chronic bronchitis

persistent cough >3 month for 2 consecutive years

pollutant damages epithelium—> inflammation—> neutrophils—> cytokines—> hypertrophy of goblet cells

Mucus production—> airway obstruction —> bacteria gets trapped and infection can occur due to damage of cilia from smoking

chronic bronchitis symptoms

Blue boaters-cyanosis

increased WOB

Dyspnea on exertion

Productive cough

prolonged expiration

Bronchiectasis

"Vicious cycle"

Infection—> inflammation—> destruction of elastic tissue—> dilation of airways

Proliferation of goblet cells—> increased mucus production—> bacteria gets trapped in mucus and promotes continued infection

Two types; focal and diffuse

Bronchiectasis symptoms

foul smelling purulent productive cough lasting months/years

Recurrent lower respiratory infections

Hemoptysis, dyspnea

restrictive lung disease

Decreased lung compliance

Increase effort to expand lungs (decreased expansion)

Hypoxemia during exertion can progress to hypoxemia at rest

Pathophysiology of idiopathic pulmonary fibrosis

Secondary to repeated cycles of epithelial cell activation and injury

Injury—> inflammation—> cytokines—> recruit fibroblasts —> damage tissue and secrete collagen—> stiff interstitial tissue