Ch 31 - Disorders of Ventilation and Gas Exchange

Upper Respiratory System

nose, pharynx, associated structures

Lower respiratory system

larynx, trachea, bronchi, and lungs

Conducting Zone

carriers air from the outside to the lungs (nasal cavity, pharynx, larynx, trachea, bronchi, bronchioles, terminal bronchioles)

Respiratory Zone

Where O2 and CO2 are exchanged between the air and blood (respiratory bronchioles, alveolar ducts, alveolar sacs, and alveoli)

Alveoli

air sacs found in the lungs where oxygen and carbon dioxide are exchanged between the air and the blood

• surrounded by networks of pulmonary capillaries

two types:

Type I - allow gas exchange

Type II - secrete surfactant (keeps the alveoli expanded and keeps them from collapsing)

Ventilation

mechanical movement of gas or air into and out of the lungs

Alveolar ventilation

volume of the air that enters the alveoli each minute

• portion of total ventilation that participates in the exchange of oxygen and CO2

Respiratory Membrane

formed by shared alveolar and capillary walls, is composed of

• a layer of type I and type II alveolar cells

• an epithelial basement membrane underlying the alveolar wall

• capillary basement membrane

• capillary endothelium (lining of capillaries)

Respiratory dead space

the part of the lung with no gas exchange; ONLY conduction

lung compliance

the ability of the lungs to expand in response to changes in pressure

• describes how easily the lungs inflate

elastic recoil of lung tissue

affects lung compliance

tendency of the lungs to return to their original size

• lungs naturally tend to recoil inward chest wall tends to spring outward

• opposing forces help maintain normal lung expansion

surface tension within the alveoli

affects lung compliance

surfactant reduces the surface tension

• surfactant prevents alveolar collapse during expiration

• surfactant increases lung compliance and reduces the work of breathing

decreased surfactant = increased ST

Tidal Volume (TV)

amount of air moved into and out of the lung with each breath (approx. 500 mL)

• inhalation = 500mL in

• exhalation = 500mL out

measured using pulmonary function tests (PFTs)

Vital Capacity (VC)

maximum volume of air a person can forcefully expel from their lungs after a maximum inhalation

Residual volume (RV)

amount of air that always remains in the lungs (always in the alveoli)

• air needed to keep the alveoli open

Total Lung Capacity (TLC)

the maximum volume of air the lungs can hold

• TLC = VC + RV

• approx. 6000 mL

• ask the person to take the deepest inhale then the deepest exhale

Central Chemoreceptors

located in medulla oblongata in the brainstem around respiratory center

• they reflect CO2

• stimulated by hydrogen (H+) in the cerebrospinal fluid (pH)

• increases the respiratory depth and rate (CO2 = H+)

for better understanding, look at slide 15 of lecture

Peripheral Chemoreceptors

located in the aorta and carotid bodies

• stimulated by hypoxemia (low oxygen in the blood)

• responsible for increase in ventilation that occurs in response to arterial hypoxemia

Hypercapnia

increased CO2 levels in the blood

• CO2 easily diffuses into CSF

• lowers pH and stimulates the central chemoreceptors

• increased rate and depth of respirations (hyperventilation)

Hypoxemia

decreased in blood oxygen levels (can also be caused by production of metabolic acid (acidosis - increased H+ in the blood))

• peripheral chemoreceptors respond (causes hyperventilation); important control mechanism in individuals with chronic lung disease (more hypoxia drive)

Hypoxia Drive

mechanism where body relies on the low arterial oxygen levels (PaO2) to stimulate breathing rather than the primary stimulus (high arteries CO2 levels (PaCO2))

• this becomes the primary control of respiration in chronic respiratory conditions (COPD) and cystic fibrosis due to:

  • hypercapnic desensitization

  • shift to peripheral chemoreceptors

hypercapnic desensitization

chronic hypercapnia makes the central chemoreceptors become less sensitive to high carbon dioxide levels

• central chemoreceptors no longer control

Shift to peripheral chemoreceptors

breathing control shifts to peripheral chemoreceptors that respond to decreased arterial oxygen (PaO2 < 60 mmHg)

Hypoxia Drive Pathophysiology

1. Chronic elevation of CO2 levels

2. Medullary chemoreceptors become insensitive to high PCO2

3. PCO2 increases, PO2 decreases slightly

4. No increase in respiration to compensate occurs

5. Marked decreased in O2 levels

6. very low PO2 stimulates the peripheral chemoreceptors (in aortic arch and common carotid arteries)

7. inspiratory muscles stimulates

8. increased respirations

9. remove CO2 and take in more O2

10. PCO2 decreases, PO2 increases

11. Respiration slows

12. Cycle repeats

Mild hypoxemia

activation of the CNS that causes

• increased HR

• peripheral vasoconstriction

• diaphoresis - sweating

• increase in BP

manifestation of hypoxemia

chronic hypoexmia

often presents with insidious (gradually causes harm, unnoticeable at first) manifestations

• increased ventilation

• increased production of RBCs; hypoxia stimulates erythropoietin secretion

• cyanosis - decreased oxygenation of RBCs

manifestations of hypoxemia

Eupnea

normal breathing pattern

• 12-20 BPM (14-20 according to lecture)

tachypnea

abnormally fast breathing

bradypnea

abnormally slow breathing

apnea

cessation of breathing

Kussmaul Respirations (hyperpnea)

slightly increased ventilatory rate, very large tidal volume, and no expiratory pause

• very fast breathing that is commonly seen in diabetic ketoacidosis (DKA)

Cheyne-Strokes Respirations

alternates between deeper and faster breathing and shallower breathing, culminating in a period of apnea before the cycle repeats

• associated with heart failure and neurological conditions

Dyspnea (+ severe dyspnea and dyspnea on exertion)

subjective sensation of uncomfortable breathing described as SOB (difficulty breathing)

• severe dyspnea causing flaring of the nostrils, use of accessory muscles of respiration

• dyspnea on exertion causes SOB with activity

manifestation of respiratory disorders

Orthopnea

dyspnea when lying down

manifestation of respiratory disorders

Wheezing

high-pitched whistling sounds during breathing caused by narrowed airways

manifestation of respiratory disorders

Hemopysis

coughing up blood or bloody secretions (sputum)

• result of erosion of lung tissue or BVs, commonly seen in pulmonary TB

manifestation of respiratory disorders

Cough

protective reflex that helps clear the airways by an explosive expiration

• productive cough (wet) - brings up sputum

• non productive cough (dry) - does not bring up sputum or mucus, characterized as “hacking”

manifestation of respiratory disorders

Abnormal Sputum

manifestation of respiratory disorders

changes in the amount, consistency, color, and odor provide information about the progression of disease and the effectiveness of therapy

Pneumothorax

air accumulation in the pleural cavity causing the lung to partially or completely collapse

• manifestations:

  • chest pain

  • dyspnea an tachypnea

  • reduced breath sounds

Closed Pneumothorax

air can enter the pleural cavity from internal airways

• no opening in the chest wall (no external openings in the chest wall, all comes internal)

• erosion from internal side

Secondary Pneumothorax

associated with underlying respiratory disease

• rupture of emphysematous bleb or erosion by a tumor)

Open Traumatic Pneumothorax

result of trauma to the lungs; atmospheric air enters the pleural cavity through an opening in the chest wall (external) - “sucking” wound on chest

Tension Pneumothorax

occurs when an opening in the chest wall or lung tissue allows the air to enter the pleural cavity during inhalation but prevents it from escaping during exhalation

• trapped air accumulates, causing increased pressure within the pleural space; most serious form

Pleural Effusion

presence of excessive fluid in the pleural cavity

• increased pressure in the pleural cavity

Exudative effusions vs transudative effusions (two main types of pleural effusion)

exudative effusions → in response to inflammation

• purulent drainage (empyema)

• blood (hemothroax)

transudative effusions → result of increased hydrostatic pressure or decreased osmotic pressure in the blood vessels (non-inflammatory)

• water effusions (hydrothorax)

Manifestations + management of pleural effusions

manifestations

chest pain → unliateral, localized to lower and lateral part of the chest

• becomes worse with chest movements

dullness → dullness to percussion and absence of breath sounds over the affected area

dry cough

management

thoracocentesis → chest drainage is performed to remove fluid + relieve pressure

Atelectasis

incomplete expansion of the lung or portion of the lung leading to collapse

• causes impaired gas exchange and hypoxia

• alveoli become airless and inflammation or atrophy occur

• interferes with bloodflow through the lung (when alveoli receive no oxygen, nearby pulmonary BVs constrict)

• both ventilation and perfusion are altered (diminished/absent gas exchange)

Obstructive, compression, and postoperative atelectasis

obstructive - caused by total obstruction of the airway

compression - external mass or tumor exerts pressure on part of lung

postoperative - can occur after surgery

COPD

groups of chronic respiratory disorders that cause irreversible and progressive dmg to lungs

• characterized by long-term breathing difficulties and airflow limitation

• may lead to the development of respiratory failure and cor pulmonae (right-sided heart failure)

causes and risks for COPD

tobacco smoke, second hand smoke exposure

prolonged exposure to air pollution, chemicals, fumes, dust

genetic factors - alpha 1-antitrypsin deficiency (genetic disorder that leads to early-onset emphysema even in non-smokers)

Bronchial Smooth Muscle

found in the walls of the bronchi and bronchioles

• controls the diameter of the airways, regulating how much air enters and leaves the lungs

• bronchial smooth muscle is innervated by the autonomic NS (parasympathetic and sympathetic

  • Parasympathetic is vasal control (bronchoconstriction)

  • Sympathetic is Beta 2-adrenergic receptor control (bronchodilator)

• presence or absence of airway secretions can also influence airway patency

asthma (+ extrinsic and intrinsic asthma)

bronchial obstruction occurs in person with hypersensitive or hyperresponsive airways

• most common chronic disease in kids

• inflammation of the mucosa with edema, bronchoconstriction caused by smooth muscle contraction and increased secretion of thick mucus occurs, blocking the airways

extrinsic asthma → acute episodes triggered by type I hypersensitivity (common in kids, allergic reactions)

intrinsic asthama → triggered by cold, respiratory infections, stress (onset during adulthood)

slide 36 gives pathogenesis - review

Early phase and late phase asthma

early phase - 5-60 minutes; exposure to collagen IgEs bind to mast cells; sensitized mast cells release histamine (causing inflammatory response)

• bronchoconstriction, increased mucus secretion, and attraction to other immune cells occurs

late phase - 4-24 hours; recruitment of eosinophils and sustained inflammation (repeated inflammatory episodes and injury)

Manifestations of Asthma

• inhalation → bronchial lumen expand slightly

• exhalation → becomes prolonged due to obstruction (accessory muscles are used)

• forced expiratory volume decreased and residual volume is increased

• dyspnea (causing air trapping)

• wheezing

• CO2 retention, hypoxemia

Status Asthamticus

when medication does not relieve asthma; persistent attack of asthma

• fatal b/c of severe hypoxia and acidosis

Asthma pH changes

initial → mild respiratory alkalosis caused by hyperventilation

prolonged → causes respiratory acidosis due to airway obstruction and air trapping

Management of Asthma

pulmonary function studies assess and monitor asthma

• peak expiratory flow rate (measures the speed to expiration)

treatment - short and long term acting B2 agonists (albuterol) and corticosteroids

Emphysema

abnormally permanent enlargement of air spaces distal to terminal bronchioles

• destruction of alveolar walls and septae leads to large, permanently inflated alveolar air spaces

  • hypercapnia (chronic elevation)

  • hypoxic drive becomes driving force of respiration

• genetic deficiency, smoking, pathogenic bacteria are contributing factors

Smoking and how it causes alpha 1-antitrypsin deficiency + emphysema

1. smoking

2. attraction of inflammatory cells

3. release of elastase

4. action inhibited by alpha1-antitrypsin

5. decreased alpha1-antitrypsin activity or inherited alpha1-antitrypsin deficiency

6. destruction of elastic fibers in lung

7. emphysema

alpha 1-antitrypsin

protein produced mainly by the liver used to protect the lungs from damage caused by neutrophil elastase

process occurs in the following steps

1. genetic deficiency → abnormal genes produce insufficient alpha 1-antitrypsin

2. inflammation attracts neutrophils

3. neutrophils release elastase to breakdown harmful bacteria and potentially damage elastic fibers in the lungs (Normally alpha -1antitrypsin inhibits elastase and coats lungs protecting them from neutrophil elastase)

4. Alpha -1antitrypsin deficiency - uninhibited elastase cause destruction of elastic fibers in the lungs

Pathologic changes in emphysema

breakdown of alveolar walls caused loss of surface area of gas exchange, loss of pulmonary capillaries, and altered ventilation-perfusion ratio (mismatch between air reaching alveoli and blood flow in pulmonary capillaries)

fibrosis causing weakening of walls and narrowing in airways that causes interference with passive expiratory airflow - difficulty to remove air from lungs

Manifestations of Emphysema

progressive difficulty with expiration causing air trapping and increase in residual volume

• Overinflation of the lungs

• Barrel chest: fixation of ribs in respiratory position, increased anterior-posterior diameter of thorax

• Flattened diaphragm (on radiographs)

• “Pink Puffer” – shortness of breath and pink color of the skin: no cyanosis until late stage of the disease.

• Pursed-lip breathing –- prolonged expiration using accessory muscle

Management of Emphysema

• Injections of donor alpha-1 antitrypsin

• Anti-inflammatory drugs

• Bronchodilators – medications relax bronchial smooth muscles, widen the airways, and improve airflow.

• Oxygen therapy as condition advances

• In late stages –- lung reduction surgery and lung transplant

Chronic Bronchitis

inflammation, obstruction, and repeated infection in bronchi with excessive mucus production, resulting in persistent coughing and difficulty breathing

• Clinical definition: productive cough lasting at least 3 months per year for 2 consecutive years, after excluding other possible causes

Causes and risk factors of chronic bronchitis

• Increased risk with history of cigarette smoking or living in urban or industrial area

• Chronic irritation from smoke cause inflammation and swelling in mucosa in large and small bronchi and overproduction of mucus

Pathogenesis of Chronic Bronchitis

chronic inflammation causes obstructive narrowing or airways

• In large bronchi: increase in goblet cells and squamous metaplasia of ciliary epithelial cells

  • impaired ciliary function: build-up of mucus plugs in airways.

• In small bronchi: smooth muscle hyperplasia and fibrosis: thickening walls and narrowing of bronchial lumen –- increased airway resistance

Manifestations of Chronic Bronchitis

• Manifestations develop gradually – chronic productive cough in early stages.

• In advanced stages dyspnea and wheezing

• Pulmonary hypertension due to fibrosis in pulmonary capillaries cause cor pulmonale – right-sided heart failure

• Peripheral edema –- back up effect of right sided heart failure

• “Blue Bloater” – cyanosis and fluid retention due to right-sided heart failure (advanced stages)

Blue bloated vs pink buffer

blue bloater → chronic bronchitis

pink puffer → emphysema

slide 55

Bronchiectasis

abnormal irreversible dilation of the medium-sized bronchi

• Result of weakening of muscle and elastic fibers in bronchial walls, causing permanent damage and abnormal dilation

• Bronchiectasis develops when repeated inflammation or infection damages the bronchial walls.

• impaired bronchial drainage causes recurrent infections by streptococci, staphylococci, pneumococci, H. influenzae

Manifestations of Bronchiectasis

Chronic productive cough with large amounts of sputum

Rales and rhonchi in the lungs –- light (rales, bubbly) and harsh (rhonchi, snoring) sounds

Foul breath – due to persistent bacterial infection

Dyspnea

Hemoptysis due to damaged bronchial blood vessels

Cystic Fibrosis (CF)

inherited genetic disorder that affects the lungs, pancreas, digestive system, and other organs.

• It causes the body to produce thick, stick mucus

• Tenacious thick mucus from exocrine glands obstructs airways, pancreatic, bile ducts

Causes of CF

➢ Autosomal recessive disorder, abnormal CFTR gene located on chromosome 7

➢ Most common inherited disease in Caucasians

➢ 1 in 25 Caucasian Americans is carrier of the gene

CFTR gene

provides instructions to protein channel on the surface of cells to control the flow of chloride ions and water

• mutations of this gene cause abnormal transport of chloride ions and water with excessive sodium secretion and formation of thick mucus

slide 59 has a table

Pathogenesis of Cystic Fibrosis

1. In airways and lungs thick mucus obstructs airflow and impairs drainage leading to chronic, persistent lung infections

2. Results in permanent damage to bronchial walls development of cor pulmonale

3. In digestive tract

• Bowel obstruction in newborns

• Pancreatitis – caused by blockage of pancreatic ducts

• Cirrhosis of the liver –- due to obstruction of bile duct

4. Sweat glands: high sodium chloride content

diagram on slide 61

Manifestations of CF

• Meconium ileus may occur at birth –- due to intestinal obstruction

• Salty skin – due to increased salt concentration in sweat.

• Signs of malabsorption: steatorrhea –- fatty stool abdominal distention

• Chronic cough and frequent respiratory infections

• Dehydration: excessive salt loss through sweating can contribute to dehydration.

• failure to meet normal growth milestones

Screening of CF

Screening in newborn:

• Specific pancreatic protein –- blood spot test

• Sweat test – 2 positive tests with elevated NaCl

• Require confirmation

• Genetic testing

diagram on slide 63