07 - Pulmonary Pathophysiology

what is the respiratory tract

pathway through which gases enter and exit the lungs

what does the respiratory tract consist of

mouth/ nose → pharnyx → larnyx → trachea → bronchi → alverolar sacs

mouth/ nasal cavity

opening of the respiratory tract

pharynx

shared between digestive and respiratory system

located behind mouth

larynx

vocal cords

underneath pharnyx

what is the trachea surrounded by

surrounded by rings of cartilage that make it rigid and prevent its collapse.

rigidity is termed airway patency

trachea vs esophagus difference

trachea can not collapse

esophagus collapses when not in use

apnea

cessation of breathing

lack of open airway

when does apnea usually happen

generally occurs when the upper airway muscles surrounding the trachea are relaxed during sleep.

These muscles, when active, help to “pull on” the trachea keeping it open (patent) and preventing collapse.

apnea is often causesd by

obesity

obstructive sleep apnea

When the upper airway muscles relax, the excess weight in the throat and neck push on the trachea and cause it to collapse

90% of sleep apnea cases

central sleep apnea

abnormalities in the respiratory control centres in the brain

other 10% of sleep apnea cases

glottis

The opening of the trachea

epiglottis

flap of tissue acts as a barrier to prevent ingested food and drink from entering the trachea rather than the glottis

how is glottis controlled

controlled by a laryngeal branch of the vagus nerve. The epiglottis covers the glottis during the swallowing reflex.

branching of trachea

form two primary bronchi

they branch into secondary bronchi, tertiary

bronchi and so on - normally there are between twenty to twenty-five orders of bronchi branching

All of these orders of bronchi end in

what are called terminal bronchi

which have little offshoots called respiratory bronchioles that end in

alveolar sacs.

humans breathe as a reponse to what

contraction of the diaphragm (the major respiratory muscle).

contracting of the diaphram

diaphragm contracts and moves downward (towards the abdomen).

this causes the chest and the lungs to expand essentially “sucking” air into the lungs through the mouth and nostrils.

how is the diaphram controlled

controlled by the phrenic nerve

fires during inspritation

location of phrenic nerve

the phrenic nerve leaves the spinal cord in the region of the neck. It then travels downward through the body cavity to innervate the diaphragm which sits at the border of the chest and abdomen.

A beneficial consequence of this is that a relatively high spinal injury will not prevent breathing as long as the injury is below the location that the phrenic nerve comes off the spinal cord

Inspiration

brings oxygen into lungs

Expiration

expels oxygen from lungs

How does gas exchange occur in the lungs?

Blood picks up oxygen from lung gas and releases CO₂ into the lung gas, which is expelled during exhalation.

How does gas exchange occur in tissues?

Blood delivers oxygen to metabolically active tissues and picks up CO₂, a metabolic waste product.

So, how do we transport O2 from the lungs to the tissues and how do we transport CO2 from the tissues to the lungs?

Haemoglobin

Where is haemoglobin found?

Haemoglobin is packaged within red blood cells (RBCs)

What is the structure of haemoglobin?

Haemoglobin consists of 4 globin subunits: 2 alpha and 2 beta subunits.

What is the role of the heme group in haemoglobin?

Each subunit contains a heme group with an iron (Fe) molecule at its center, where oxygen binds.

hemoglobin role in binding co

Carbon monoxide (CO) binds to haemoglobin at the same site that oxygen binds.

oxygen vs co binding hemoglobin

oxygen binds relatively “loosely”.

Oxygen goes on and comes off of haemoglobin relatively easily

Carbon monoxide binds to haemoglobin and it doesn’t come off (at least not for several days and only then if you are still alive). This is why CO is so dangerous

Carbon Monoxide Poisoning

CO binds to haemoglobin at the same site that oxygen does but it doesn’t come off. If CO is bound to haemoglobin, then oxygen cannot bind and we cannot get oxygen from the lungs to the tissues.

What are pulmonary function tests used for?

Pulmonary function tests measure lung volumes and help diagnose lung disorders.

What are the two main types of lung diseases?

restrictive or obstructive.

restrictive pulmonary disease

interferes with lung expansion,

affects inspiration,

may be caused by damage to the chest wall, the lungs or the pleura.

harder to exhale

Examples of restrictive pulmonary diseases

include pulmonary edema, - expansion of the alveoli is inhibited by fluid in the lungs.

Pulmonary fibrosis and asbestosis are also restrictive diseases.

obstructive [ulmonary disease

hinder expiration.

Since air does not leave the lungs efficiently, the lungs over-inflate.

harder to inhale

examples of obstructive disorders.

Diseases that damage the alveoli, such as asthma or emphysema

How is asthma classified?

Asthma is a heterogeneous disease,

classified as

• allergic vs. non-allergic

• adult-onset vs. child-onset.

• based on the type of immune cells that mediate or trigger various pathologies

What are the three major pathologies of asthma?

1. Inflammation and swelling of the airways

2. Excessive mucus production

3. Reduction in airway diameter (caused by other 2)

major symptoms of asthma

wheezing, shortness of breth, cough, chest tightness, airflow obstruction

COPD

Chronic obstructive pulmonary diseases (COPD)

What two diseases make up COPD?

Chronic bronchitis and emphysema.

What is chronic bronchitis?

Bronchitis is a disease in which there is inflammation and narrowing of

the airways. This increases the resistance to airflow and makes it harder to breathe out (exhale).

Emphysema

a disease in which there is breakdown of the alveolar walls. This reduces the elastic recoil of the lungs when they return to a deflated state from an inflated state. This also reduces airflow

during exhalation.

how is copd defined

defined by airflow obstruction, chronic respiratory symptoms and a risk factor

such as smoking or exposure to pollution

how is copd diagnosed

Clinically, COPD is the diagnosis as it is hard to distinguish between the effects of chronic bronchitis

and emphysema. Emphysema can only be confirmed upon autopsy

What is the most common respiratory condition?

COPD is the most common respiratory affliction.

Pulmonary Fibrosis

a Restrictive Lung Disease

Pulmonary fibrosis is a condition in which the lung tissue becomes damaged and scarred.

This makes it stiffer and harder to expand.

This makes it harder to inhale and get air into the lungs.

Idiopathic pulmonary fibrosis (IPF)

is a form of interstitial (extracellular) fibrosis that develops in the absence of a clear precipitating factor. It is not curable.

The deposition of fibrous material within the alveoli increases the diffusion barrier for oxygen to move from the lung gas into the blood and for CO2 to move from the blood into the lung gas.

What type of virus is COVID-19? and what system does it infect

COVID-19 is a SARS-like coronavirus that infects the respiratory system.

What are the primary cells infected by COVID-19?

Pneumocytes (alveolar wall cells)

Bronchial epithelial cells (airway walls)

Capillary endothelial cells (pulmonary capillaries)

How does COVID-19 enter host cells?

The virus uses its spike protein to bind to the ACE2 receptor, allowing entry into cells.

What happens when COVID-19 infects bronchial epithelial cells?

It triggers inflammation, leading to tracheal narrowing and bronchitis, causing obstructive lung disease.

harder to exhale

What happens when COVID-19 infects alveolar cells?

The immune response causes fibrosis (scar tissue formation), leading to restrictive lung disease.

intubate

insert a tube into the trachea to allow for artificial ventilation

decision to intubate is based on a

number of factors

Refractory hypoxemia

Hypercapnia

Hemodynamic instability

Refractory hypoxemia

low level of blood oxygenation despite the inspired oxygen level being sufficient to, lead to a normal level of oxygenation.

Hypercapnia

in this case refers to an increase in the partial pressure of carbon dioxide

(PCO2) in the arterial blood. Since CO2 in an aqueous solution is an acid,

increased CO2 levels lead to a decrease in pH in the blood (acisiosis)

Hemodynamic instability

refers to unstable or low blood pressure.

Why was prone positioning used for ventilated COVID-19 patients?

Lying on the front (prone) improved lung aeration in arease that were not ventilated, allowing for better gas exchange compared to lying on the back (supine).

What is long COVID?

The persistence of symptoms after clearing the infection, possibly due to immune dysfunction or autoimmune responses.

What are potential causes of long COVID?

Immune system dysfunction

Inappropriate autoimmune responses

In some cases, prolonged virus presence in the body

What is the general definition of sleep?

Sleep is a cyclically occurring state of decreased motor activity and perception, occurring in various stages where neurons range from very quiescent to extremely active.

What are some possible purposes of sleep?

1. Brain maturation during development

2. Strengthening synaptic connections

3. Enhancing the immune system

How can sleep stages be identified?

Sleep stages can be determined using EEG activity (electroencephalography).

What are the two main types of sleep?

1. Slow-Wave Sleep (SWS) – four stages of progressively deeper sleep

2. Rapid Eye Movement (REM) Sleep – associated with dreaming and brain activity

How does the sleep cycle change over the course of the night?

As sleep progresses, we spend more time in REM sleep and less time in SWS, particularly in stages 1 and 2.

What are the characteristics of slow-wave sleep (SWS)?

• Low-frequency EEG waves

• Decreased muscle tone

• Mostly decreased brain activity

• Increased parasympathetic activity

• Some logical dreams and possible snoring

What are the characteristics of REM sleep?

• High brain activity

• Muscle atonia (paralysis)

• Most dreams occur here

• Rapid eye movements

What is narcolepsy?

A neurological disorder where REM sleep intrudes into wakefulness.

What are the four key symptoms of narcolepsy?

Excessive daytime sleepiness

Cataplexy – sudden muscle weakness triggered by strong emotions

Sleep paralysis – temporary inability to move when falling asleep or waking up

Hypnagogic hallucinations – vivid, dream-like images at sleep onset

Obstructive Sleep Apnea Case Study - Key physiological responses include:

1. Reduced rib cage movement due to airway obstruction.

2. Declining blood oxygen levels as breathing stops.

3. Temporary airway opening, allowing deep breaths and oxygen recovery.

4. Heart rate and blood pressure spikes, stressing the cardiovascular system and increasing the risk of heart attacks and strokes.

EEG (brain activity), rib cage movement, and blood oxygen levels can help diagnose sleep apnea episodes.

Partial Paralysis of the Diaphragm Case Study - key findings

• While awake, she breathes relatively normally (using her other msucels intercostal and abdominal muscles), maintaining normal blood oxygen levels.

• During slow-wave sleep, breathing effort decreases slightly, but oxygen levels remain stable.

• In REM sleep, postural muscle paralysis (a normal REM phenomenon) affects the intercostal muscles, drastically reducing rib cage movement. Since her diaphragm is impaired, she relies only on abdominal muscles, leading to decreased airflow and lower blood oxygen levels.

Higher brain centres

are not critical for breathing although they can/do have influence over breathing

during wakefulness that isn’t really noticed until sleep occurs.

corticospinal tract

the connection between the cerebral

cortex and the brainstem is called the corticospinal tract. The lack of voluntary control of breathing

during sleep can lead to some sleep-related breathing disorders.

Ondine's Curse

refers to a failure of automatic breathing when asleep. When awake we have some conscious influence over our breathing even though breathing is mostly an automatic process controlled by the brainstem

Ondine’s Curse Case Study

key finidnsg s

• Blood-gas levels indicate respiratory failure (low oxygen, high carbon dioxide, acidic pH).

• Chest X-ray shows cardiomegaly, high blood pressure, and fluid in the lungs.

• ECG suggests coronary ischemia, a potential heart attack risk.

She enters a coma, requires mechanical ventilation, and is later discharged. However, she is readmitted months later with the same symptoms. Tests confirm Ondine’s Curse, a disorder where automatic breathing fails during sleep.

Her treatment requires nighttime mechanical ventilation to ensure breathing while asleep.

What enzyme catalyzes the CO₂ hydration-dehydration reaction?

Carbonic anhydrase (CA).

What is the chemical reaction for CO₂ hydration in an aqueous solution?

CO₂ + H₂O ⇌ H₂CO₃ ⇌ HCO₃⁻ + H⁺

How does CO₂ function as an acid in an aqueous solution?

CO₂ dissolves in water to form carbonic acid (H₂CO₃), which dissociates into HCO₃⁻ and H⁺, increasing acidity (lowering pH).

What happens when CO₂ is added to a system?

The reaction shifts toward producing HCO₃⁻ and H⁺, leading to a decrease in pH.

What happens when CO₂ is removed from a system?

The reaction shifts toward producing more CO₂ by combining HCO₃⁻ and H⁺, increasing pH.

Why does an increase in CO₂ lead to a decrease in pH?

Higher CO₂ levels increase H⁺ concentration, which lowers pH.

What physiological processes involve the CO₂ hydration-dehydration reaction?

CO₂ sensing in the brain, gas transport in red blood cells, HCl secretion in the stomach, and acid-base balance in the kidneys.

What role does HCO₃⁻ (bicarbonate) play at physiological pH levels?

It acts as a buffer, helping to regulate pH.