• Gas exchange in the alveolus takes 0.25 seconds—1/3 of the transit time of the erythrocyte. As a result, conditions that thicken the alveolar septum (fibrosis, cellular hypertrophy) can easily reduce the exchange of oxygen between the alveolar air and the hemoglobin-laden erythrocytes.
• The entire blood volume—about 5 litres in humans—passes through the lung each minute. In animals with pulmonary intravascular macrophages, the lung is effective in removing foreign material such as bacteria, and is a prime target organ of endotoxemia. However, conditions that impair blood flow through the lung will result in right heart failure, a condition known as cor pulmonale.
• The total surface area of the human alveoli is about 80 m² — the size of a tennis court. Imagine having to keep a tennis court sterile! Without water!
• Human lung contains about 20,000 acini and 480,000,000 alveoli. Each mm³ of human lung contains 170 alveoli.
• A person inspires about 10,000 litres of air daily. An effective system of defence is essential to protect the lung from the particles that accompany this inhaled air.

Endocrine functions of the lung include angiotensin metabolism and prostaglandin production.

Biotransformation of some toxins occurs in the lung. Club cells and type II pneumocytes, like hepatocytes in the liver, convert some chemicals and drugs to reactive intermediates, which are then detoxified to compounds that can be more easily excreted. However, if these reactive intermediates cannot be adequately detoxified, they may react with membrane lipids and injure resident cells of the lung.

Pulmonary mechanics and gas exchange

Pulmonary compliance measures how easily the lung expands. It is defined by the change in lung volume resulting from a given change in transpleural pressure (ΔV/ΔP). For non-mathematical thinkers: with normal compliance, chest expansion induces a big change in volume during inspiration and expiration; with reduced compliance, the same effort gives a lower tidal volume.

Airway resistance is the difficulty with which air flows through the airways. It is increased by bronchoconstriction, exudates in the airway lumen, or edema and inflammation of airway wall. Normally, most airway resistance is in the larger airways & nasopharynx, so partial obstruction of the upper airways has a big effect on lung function.

Causes of hypoxemia

• Hypoventilation: due to respiratory depression, weak respiratory muscles, chest injury, upper airway obstruction, airway diseases. These changes reduce lung compliance and/or increase airway resistance. If the lungs are not ventilated, gas exchange cannot occur.
• Impaired diffusion: due to diseases affecting the alveolar septum. These especially induce hypoxemia, because O₂ diffusion takes 0.3 sec, while capillary transit time for blood is only 0.75 sec. CO₂ diffuses more readily than O₂; therefore, barriers to diffusion of gas across the alveolar wall tend to cause hypoxemia but not hypercapnea, unless they also alter the matching of ventilation and perfusion.
• Ventilation-perfusion mismatching: In poorly ventilated areas of lung, blood supply is diminished because of alveolar hypoxic vasoconstriction. However, inflammation can cause dilation of these blood vessels, so that non-oxygenated blood flows past the non-ventilated alveoli to reach the systemic circulation and thus causes hypoxemia.

Shunts: congenital anomalies that may cause right-to-left shunting. As above, this can cause severe hypoxemia, because non-oxygenated blood reaches the systemic circulation.

Key points

The conducting system of the respiratory system includes the nasal cavity, trachea, bronchi, and bronchioles. It is lined by ciliated epithelium and covered by a layer of mucus, and functions to warm and humidify the inspired air, remove inhaled particles, and protect the lung against infection.

The alveoli are mainly lined by type I pneumocytes, which have very little cytoplasm. The thinness of the type I pneumocytes and the lack of interstitial connective tissue in the alveolar septa are essential for normal gas exchange and maintaining pulmonary compliance, but make the lung susceptible to injury.

Type II pneumocytes are cuboidal epithelial cells lining alveoli, which are the regenerative cells that replaces injured type I pneumocytes, and also metabolize toxins and produce surfactant.

Alveolar macrophages are present in normal lung, and function to remove inhaled particles including bacteria.

Pulmonary Defences

The necessary function of gas exchange requires that the lung remains exposed to the environment. Thus, the sterility of the lung is continuously challenged by micro-organisms and foreign material in inhaled air, and by opportunistic pathogens within droplets that are aspirated from the non-sterile upper respiratory tract. Despite this constant challenge, the lung must remain sterile, or at least minimally contaminated, because excessive numbers of bacteria induce inflammation, and inflammation impedes gas exchange in the lung. Thus, the lung requires a multi-layered system of defence against infectious agents, including mucociliary clearance, antibodies and innate defence proteins, alveolar macrophages, and neutrophils.

If the infection cannot be contained by mucociliary clearance and defence proteins, inflammation is triggered in an attempt to control the threat: alveolar macrophages produce inflammatory mediators that recruit neutrophils and more macrophages to the site of invasion, and increase the production of antibacterial proteins by airway epithelial cells. But this response has the potential to do harm: inflammatory exudates impair gas exchange, leukocyte-derived enzymes and oxygen radicals cause injury to lung tissue, and repair processes organize alveolar exudates into fibrous tissue that permanently decreases lung compliance and thickens the blood-gas barrier.

Deposition and clearance of inhaled particulates

Important particulates include infectious agents, allergens, dusts, and inert particles (e.g. asbestos, silica). The nasal cavity removes most particles >10 mm in diameter. Most 3-10 mm diameter particles lodge in the trachea and bronchi, and are removed by the mucociliary apparatus. 0.1-5 mm particles, such as bacteria, may reach terminal airways.

Airway mucus is secreted by goblet cells and by bronchial mucosal glands. The secretions of these glands cover the epithelial surface; they form a lower aqueous layer in which the cilia beat, and a superficial mucus blanket that traps particles and carries them upward. Mucus contains many protective substances:

• Defensins, cathelicidins, lysozyme, complement, and lactoperoxidase cause direct damage to microbes.
• Immunoglobulin A blocks attachment of bacteria to mucosal surfaces.
• Immunoglobulin G, complement C3b, and surfactant proteins A & D opsonize bacteria and make them tastier for macrophages.
• Lactoferrin binds iron and makes it unavailable for pathogens.

Alveolar macrophages are derived from blood monocytes, or from macrophages that replicate in the lung. Particulates that reach the alveoli are engulfed within 2 hours by alveolar macrophages, and this is enhanced if particles are opsonized by antibody, complement, or surfactant proteins. Macrophages kill bacteria using oxygen radicals, nitric oxide, and lysosomal enzymes. They also call more neutrophils and macrophages to the site of infection.

Pulmonary intravascular macrophages reside within the capillaries of the alveolar septa. Pulmonary intravascular macrophages are present in pigs, horses, ruminants, and cats, but not in healthy rodents, dogs, or humans. These cells remove infectious agents and other particles from blood, similar to stellate macrophages (Kupffer cells) in liver and macrophages in splenic sinusoids. In species that have pulmonary intravascular macrophages, sepsis tends to target the lung, causing pulmonary edema and dyspnea.

How are respiratory defences overcome?

• Aspiration pneumonia: exposure to an overwhleming number of bacteria.
• Viruses predispose to bacterial pneumonia by damaging the airway epithelium and reducing mucociliary clearance by reducing the secretion of antimicrobial peptides and by impairing the function of alveolar macrophages.
• Mycoplasma and Bordetella adhere to cilia and impair mucociliary clearance.
• Stresses and adverse climatic conditions are important causes of reduced lung defence. Stress reduces alveolar macrophage function and pulmonary immune responses, and inhibits production of antimicrobial peptides. Cold-stressed animals have reduced mucociliary function.
• Immunosuppressive drugs reduce pulmonary immune responses.
• Neutropenia deprives the lung of a major defence mechanism: neutrophils.
• Pollutants and toxic gases, for example in poorly ventilated or overcrowded barns, may reduce the ciliary function in airway epithelial cells.
• Genetic disorders are a rare cause of impaired lung defences. Ciliary dyskinesis: affected cilia lack the normal dynein arms, so ciliary beating is abnormal. Cystic fibrosis in children: altered ion exchange results in viscous airway mucus which cannot be adequately propelled to the pharynx.

Common artefacts

The following photos illustrate some normal features that can be confused with lesions, and some common artefacts.

 

 

Answer:

Normal nasal anatomy in a cow (left) and Yorkshire terrier dog (right). Identify the nasal meatuses, dorsal, middle, & ventral concha (turbinates), ethmoid conchae, nasopharynx, and the thin cribriform plate separating the nasal cavity from the olfactory lobe of the brain.