Respiratory

Functional Anatomy of the Respiratory System

The respiratory system is divided into two functional zones.

Important alveolar cells

Remember: Type I cells are specialized for diffusion; Type II cells produce surfactant.

Dual blood supply of the lungs

• Pulmonary circulation: carries blood from the right ventricle to pulmonary capillaries for gas exchange. It is a low-pressure, low-resistance circulation.
• Bronchial circulation: supplies oxygenated systemic blood to the supporting tissues of the airways and lungs.

Mechanics of Breathing

Inspiration and expiration

Normal quiet inspiration is an active process, while quiet expiration is mainly passive.

Forced breathing

Pressure relationships

• Atmospheric pressure: pressure of the surrounding air.
• Intrapleural pressure: normally negative relative to atmospheric pressure.
• Alveolar pressure: changes during breathing and drives airflow.
• Transpulmonary pressure: alveolar pressure minus intrapleural pressure; distends the lungs.

Exam tip: Airflow depends on the pressure gradient between the atmosphere and alveoli, whereas transpulmonary pressure helps determine lung expansion.

Compliance, Elastance and Surfactant

Lung compliance

Compliance describes how easily the lungs expand for a given change in transpulmonary pressure.

• High compliance: lungs expand easily.
• Low compliance: lungs are stiff and require more pressure to expand.
• Elastance is the tendency to recoil; it is inversely related to compliance.

Changes in compliance

Functional residual capacity (FRC)

FRC is the volume remaining in the lungs at the end of a normal, quiet expiration.

FRC=ERV+RV

It represents the balance between the inward elastic recoil of the lungs and the outward recoil of the chest wall.

Clinical importance:

• FRC is reduced in the supine position, obesity and pregnancy.
• FRC is often increased in obstructive disease, particularly emphysema, due to air trapping.
• A reduced FRC decreases the oxygen reservoir available between breaths.

Surfactant

Surfactant is produced by Type II pneumocytes and lowers alveolar surface tension.

Laplace's law:

P = 2T / r

Where P is the pressure required to keep an idealized spherical alveolus open, T is surface tension and r is radius.

For a given surface tension, a smaller alveolus would require greater pressure to remain open. Surfactant lowers surface tension, especially at smaller alveolar sizes, helping stabilize alveoli.

Functions of surfactant

• Reduces alveolar surface tension.
• Increases lung compliance.
• Decreases the work of breathing.
• Helps prevent alveolar collapse, particularly at low lung volumes.
• Helps maintain alveolar stability when alveoli differ in size.

Clinical correlation: Premature infants may develop neonatal respiratory distress syndrome because surfactant production is insufficient. The result is increased surface tension, reduced compliance and a greater tendency toward atelectasis.

Airway Resistance and Airflow

Airway resistance describes the opposition to airflow through the conducting airways.

For laminar flow through a cylindrical tube, Poiseuille's relationship predicts:

A small reduction in airway radius can therefore cause a substantial increase in resistance.

Factors affecting airway resistance

Laminar versus turbulent flow

• Laminar flow: orderly movement in parallel layers; resistance follows the Poiseuille relationship.
• Turbulent flow: irregular movement with greater energy loss; more likely at high flow rates, branching points and narrowed airways.

Exam tip: Airway resistance is particularly sensitive to airway radius because resistance varies approximately with the inverse fourth power of radius during ideal laminar flow.

Lung Volumes and Capacities

Basic lung volumes

Values are approximate and vary with body size, sex, age and posture.

Lung capacities

Spirometry

• Spirometry measures moving air volumes and flows.
• Standard spirometry cannot directly measure RV, FRC or TLC because these include residual air that cannot be exhaled.
• RV-containing volumes can be measured using techniques such as body plethysmography or gas dilution methods.

Remember: If a capacity includes RV, it cannot be measured by simple spirometry alone.

Dead Space and Ventilation

Types of dead space

In healthy lungs, physiologic dead space is close to anatomic dead space. It increases when ventilated alveoli receive insufficient blood flow, as may occur in pulmonary embolism.

Alveolar ventilation and PaCO₂

• Increased alveolar ventilation lowers PaCO₂.
• Decreased alveolar ventilation raises PaCO₂.
• An increase in dead-space ventilation reduces the fraction of minute ventilation available for gas exchange.

Clinical correlation: Hypoventilation causes CO₂ retention and can produce respiratory acidosis.

Gas Exchange and Transport

Dalton's Law, Alveolar Gas and Partial Pressures

Dalton's law

The total pressure exerted by a mixture of gases equals the sum of the partial pressures of its individual gases.

At sea level, atmospheric pressure is approximately 760 mmHg. Inspired air contains about 21% oxygen, but humidification and gas exchange lower the oxygen partial pressure by the time gas reaches the alveoli.

Approximate oxygen partial pressures

Values are approximate and depend on inspired oxygen, altitude, ventilation and metabolism.

Oxygen diffusion

Oxygen moves from alveoli into pulmonary capillary blood because alveolar PO₂ is higher than the PO₂ of incoming venous blood.

The rate of gas diffusion depends on:

• Surface area available for diffusion.
• Thickness of the respiratory membrane.
• Partial-pressure gradient.
• Gas solubility.
• Molecular weight.

Fick's law predicts that diffusion increases with surface area and pressure gradient but decreases as membrane thickness increases.

Factors that impair diffusion

Diffusion limitation versus perfusion limitation

Remember: Carbon monoxide is classically diffusion-limited because it binds avidly to hemoglobin, keeping dissolved capillary CO partial pressure very low.

Oxygen Transport in Blood

Oxygen is carried in two forms:

1. Bound to hemoglobin.
2. Dissolved in plasma.

The vast majority of oxygen is hemoglobin-bound.

PaO₂ versus SaO₂ versus oxygen content

MCQ trap: Severe anemia may produce normal PaO₂ and normal SaO₂ but reduced total oxygen content.

Oxyhemoglobin dissociation curve

The relationship between PO₂ and hemoglobin saturation is sigmoid-shaped because oxygen binding is cooperative.

• At high PO₂, hemoglobin loading in the lungs is efficient.
• At lower tissue PO₂, a relatively small decline in PO₂ releases a substantial amount of oxygen.

Right versus left shift

Memory cue: Right shift = oxygen released to tissues more readily.

Bohr effect

Increased CO₂ and H⁺ reduce hemoglobin's affinity for oxygen, shifting the dissociation curve to the right. This supports oxygen unloading in metabolically active tissues.

Haldane effect

Oxygenation of hemoglobin in the lungs reduces its ability to carry CO₂ and H⁺. Deoxygenated hemoglobin in tissues can carry more CO₂ and buffer more H⁺.

Carbon monoxide poisoning

Carbon monoxide:

• Binds hemoglobin with very high affinity.
• Reduces the number of sites available for oxygen.
• Shifts the remaining oxyhemoglobin dissociation curve to the left.
• Impairs oxygen unloading to tissues.

PaO₂ may remain normal because it measures dissolved oxygen, not oxygen bound to hemoglobin. Standard pulse oximetry may also be misleading.

Clinical clue: Suspected carbon monoxide poisoning requires urgent assessment and co-oximetry where available.

Hypoxemia and Hypoxia

• Hypoxemia: abnormally low oxygen in arterial blood.
• Hypoxia: inadequate oxygen availability or utilization at the tissue level.

Hypoxemia can cause hypoxia, but tissue hypoxia may also occur despite a normal PaO₂, such as in severe anemia or cyanide poisoning.

Major types of hypoxia

Causes of hypoxemia

Alveolar–arterial oxygen gradient

The gradient helps distinguish problems that reduce alveolar oxygen from problems that impair transfer from alveoli into arterial blood.

• Normal A–a gradient with hypoxemia: consider hypoventilation or high altitude.
• Increased A–a gradient: consider V/Q mismatch, diffusion impairment or shunt.

The normal gradient increases with age and depends on inspired oxygen and clinical context.

Clinical reasoning

If PaO₂ is low:

1. Calculate or estimate alveolar PO₂.
2. Compare alveolar and arterial PO₂.
3. Interpret the A–a gradient.
4. Consider the response to supplemental oxygen.
5. Use the clinical context to distinguish hypoventilation, V/Q mismatch, diffusion impairment and shunt.

Carbon Dioxide Transport

CO₂ is transported in blood in three main forms.

Bicarbonate formation

Inside red blood cells:

Carbonic anhydrase accelerates the reaction.

• HCO₃⁻ leaves the red blood cell and enters plasma.
• Cl⁻ enters the red blood cell to maintain electrical neutrality.
• This exchange is called the chloride shift.

In the lungs, the process reverses: bicarbonate re-enters red blood cells, is converted to CO₂, and CO₂ diffuses into alveoli for expiration.

CO₂ transport: high-yield facts

• Deoxygenated hemoglobin carries more CO₂ and buffers more H⁺.
• Oxygenation in pulmonary capillaries facilitates CO₂ unloading.
• The Haldane effect supports CO₂ transport from tissues to lungs.
• The bicarbonate buffer system is central to CO₂ transport and acid-base balance.

Pulmonary Circulation and V/Q Matching

Pulmonary Pressures, Resistance and Blood Flow

The pulmonary circulation is a low-pressure, low-resistance vascular system that accommodates the entire cardiac output.

Values are approximate and depend on measurement conditions.

Hypoxic pulmonary vasoconstriction

When an alveolar region has low PO₂, its small pulmonary arteries constrict.

Purpose: Redirect blood away from poorly ventilated alveoli toward better-ventilated regions.

This improves overall ventilation-perfusion matching.

Important contrast:

• Pulmonary vessels: local alveolar hypoxia → vasoconstriction.
• Many systemic tissues: local hypoxia → vasodilation.

West zones of the lung

Regional blood flow is influenced by gravity and the relationship between alveolar and vascular pressures.

Where PA is alveolar pressure, Pa is pulmonary arterial pressure and Pv is pulmonary venous pressure.

Remember: In an upright lung, perfusion generally increases from apex to base because vascular pressures rise relative to alveolar pressure.

Pulmonary vascular resistance

Pulmonary vascular resistance is influenced by vessel recruitment, distension, lung volume and alveolar oxygen levels.

• Recruitment opens additional vessels.
• Distension enlarges vessels and reduces resistance.
• Hypoxia can increase pulmonary vascular resistance.
• Both very low and very high lung volumes can increase pulmonary vascular resistance through different mechanisms.

Chronic widespread hypoxia can lead to pulmonary hypertension and right ventricular strain.

Ventilation–Perfusion (V/Q) Ratio

The V/Q ratio compares alveolar ventilation with pulmonary blood flow.

For the lungs as a whole, a typical average V/Q ratio is approximately 0.8.

Regional V/Q variation

The apex has a higher V/Q ratio because perfusion falls more markedly than ventilation toward the top of the upright lung.

V/Q extremes

V/Q mismatch

V/Q mismatch occurs when ventilation and blood flow are distributed unevenly.

• Low V/Q: blood flow is excessive relative to ventilation.
• High V/Q: ventilation is excessive relative to blood flow.
• V/Q mismatch is a major cause of hypoxemia.
• Supplemental oxygen often improves hypoxemia caused by V/Q mismatch.

Shunt versus dead space

MCQ tip: A true shunt means blood reaches the arterial circulation without adequate exposure to ventilated alveoli. This is why oxygen alone may not fully correct severe shunt-related hypoxemia.

Mechanisms of Hypoxemia

Important distinctions

• Hypoventilation raises PaCO₂ and lowers alveolar PO₂.
• V/Q mismatch produces differences in gas exchange among lung regions.
• Diffusion impairment slows equilibration across the alveolar-capillary membrane.
• Shunt allows deoxygenated blood to bypass adequately ventilated alveoli.

Exam tip: A normal A–a gradient points toward hypoventilation or low inspired oxygen; an increased gradient suggests impaired pulmonary gas exchange.

Regulation of Respiration

Brainstem Respiratory Centers

Respiration is controlled by neural networks in the medulla and pons.

Neural control of breathing

• The medulla generates and organizes respiratory rhythm.
• The pons modifies the pattern and timing of breathing.
• Phrenic nerves activate the diaphragm.
• Intercostal nerves activate respiratory muscles.
• Chemoreceptor and mechanoreceptor feedback adjusts respiratory output.

Respiratory muscle control

• Quiet inspiration is mainly diaphragmatic.
• Increased ventilatory demand recruits accessory inspiratory muscles.
• Forced expiration recruits internal intercostal and abdominal muscles.

Protective reflexes

• Pulmonary stretch receptors respond to lung inflation.
• Irritant receptors respond to inhaled irritants and can trigger cough or rapid breathing.
• J (juxtacapillary) receptors respond to changes associated with pulmonary congestion or interstitial processes and may contribute to rapid, shallow breathing.

Chemoreceptors: PaCO₂, pH and PaO₂

Chemical feedback is central to respiratory regulation.

Central chemoreceptors

• Located near the ventrolateral medullary surface.
• Respond primarily to changes in brain extracellular fluid H⁺ generated when CO₂ crosses the blood-brain barrier.
• Increased PaCO₂ generally increases ventilatory drive.
• They are a major contributor to the ventilatory response to CO₂.

Mechanism:

Increased arterial CO₂ → CO₂ crosses the blood-brain barrier → H⁺ increases in brain extracellular fluid → central chemoreceptor stimulation → ventilation increases → PaCO₂ falls toward baseline.

Central chemoreceptors do not directly function as the main sensors of arterial oxygen.

Peripheral chemoreceptors

Peripheral chemoreceptors respond particularly strongly when PaO₂ falls substantially, classically below approximately 60 mmHg.

They also respond to hypercapnia and metabolic acidosis.

Integrated response to altered blood gases

Exam tip: Central chemoreceptors primarily sense CO₂-related changes in brain fluid pH; peripheral chemoreceptors are essential for the ventilatory response to low arterial oxygen.

Exercise and Respiratory Control

During exercise, ventilation rises to meet increased metabolic demand.

Ventilation increases through neural feed-forward signals from motor activity and feedback from chemical and mechanical receptors.

In healthy individuals, ventilation generally rises sufficiently to match increased CO₂ production during moderate exercise.

High-Altitude Adaptation

At high altitude, barometric pressure falls, reducing inspired oxygen partial pressure even though the percentage of oxygen in air remains approximately 21%.

Immediate response

• PaO₂ decreases.
• Peripheral chemoreceptors stimulate hyperventilation.
• PaCO₂ decreases.
• Respiratory alkalosis develops.

Acclimatization

High-altitude pulmonary edema (HAPE)

Uneven hypoxic pulmonary vasoconstriction can produce high pulmonary vascular pressures and stress pulmonary capillaries, contributing to fluid accumulation in the lungs.

Clinical warning signs: Breathlessness at rest, cough, reduced exercise tolerance and hypoxemia after ascent require urgent assessment and descent when HAPE is suspected.

Acid–Base Integration

Normal Arterial Blood Gas Values

Ranges vary slightly between laboratories and clinical settings.

Primary acid-base disorders

Compensation rules

Acute respiratory acidosis

For each 10 mmHg increase in PaCO₂ above 40 mmHg, HCO₃⁻ rises by approximately 1 mEq/L.

Chronic respiratory acidosis

For each 10 mmHg increase in PaCO₂ above 40 mmHg, HCO₃⁻ rises by approximately 3.5–4 mEq/L.

Acute respiratory alkalosis

For each 10 mmHg decrease in PaCO₂ below 40 mmHg, HCO₃⁻ decreases by approximately 2 mEq/L.

Chronic respiratory alkalosis

For each 10 mmHg decrease in PaCO₂ below 40 mmHg, HCO₃⁻ decreases by approximately 4–5 mEq/L.

These are approximate compensation rules; the full clinical picture and timing matter.

Pulmonary Pathophysiology

Obstructive Lung Disease

Obstructive disease increases resistance to airflow, especially during expiration. Airway narrowing, mucus, inflammation and loss of elastic recoil can limit expiratory flow.

Spirometry pattern

A post-bronchodilator FEV₁/FVC below the accepted diagnostic threshold supports airflow obstruction. The fixed ratio of 0.70 is commonly used in COPD guidelines, although age-adjusted lower limits of normal can also be important.

Asthma

Asthma is characterized by variable airway narrowing, airway hyperresponsiveness and inflammation.

Key features:

• Episodes of wheeze, cough, chest tightness or breathlessness.
• Symptoms and airflow obstruction vary over time.
• Obstruction is often reversible, spontaneously or after bronchodilator treatment.
• Eosinophils and other inflammatory cells may contribute in particular asthma phenotypes.

Chronic obstructive pulmonary disease (COPD)

COPD is characterized by persistent airflow obstruction, usually associated with chronic exposure to harmful particles or gases.

The two classic components are chronic bronchitis and emphysema.

Chronic bronchitis definition: Productive cough for at least 3 months in each of 2 consecutive years, after excluding other causes.

Emphysema: key changes

• Destruction of alveolar walls reduces surface area for gas exchange.
• Loss of elastic recoil promotes expiratory airway collapse.
• Compliance increases.
• Residual volume and often TLC increase.
• Diffusion capacity may decrease due to loss of alveolar-capillary surface area.

Asthma versus COPD

Restrictive Lung Disease

Restrictive disorders reduce lung expansion and total lung capacity.

Spirometry pattern

A low FVC alone does not establish restriction. Confirmation generally requires demonstrating a reduced TLC.

Major causes

Restrictive versus obstructive disease

Exam tip: Use the FEV₁/FVC ratio to identify an obstructive pattern, then use TLC to confirm restriction when indicated.

Pulmonary Hypertension

Pulmonary hypertension involves elevated pressure in the pulmonary circulation. It increases the workload on the right ventricle and may ultimately cause right ventricular hypertrophy and failure.

WHO clinical groups

Key mechanism

Pulmonary vascular resistance rises because of vascular remodeling, vasoconstriction, obstruction or loss of vascular bed.

This can lead to:

• Increased right ventricular afterload.
• Right ventricular hypertrophy and dilation.
• Reduced exercise tolerance.
• Peripheral edema and other signs of right-sided heart failure in advanced disease.