Alveoli are the thin-walled, sac-like, terminal dilations of the respiratory bronchioles, alveolar ducts, and alveolar sacs. They serve as the functional unit for gas exchange with pulmonary capillaries.

• The adult lung contains approximately 300 million alveoli.
• The combined maximal volume is approximately 5–6 L.
• Each alveoli is surrounded by capillaries.
• The combined surface area ranges from 50 to 100 m².

• Alveolar walls: Comprised of a thin epithelial layer that consists of alveolar type I and alveolar type II cells.
  • Alveolar type I cells are squamous epithelial cells and cover approximately 80% of the alveolar surface. They are highly differentiated and very susceptible to injury. If the type I cell is damaged, the type II cells replicate and modify to form new type I cells.
  • Alveolar type II cells are cuboidal epithelial cells that synthesize and secrete the fluid layer (surfactant) that lines the alveoli. The type II alveolar cells also control local electrolyte balance and lymphatic cell functions.
  • Alveolar type III cells are alveolar macrophages and are an important element of lung defense. They are part of the lung inflammatory response and ingest foreign materials within the alveoli.
• Alveoli size:
  • Individual alveoli range from about 75 to 300 µm.
  • Surface tension: Describes the force exhibited by water molecules in the alveoli towards one another. Water has a greater attraction to each other than to air, causing the alveoli to tend towards collapse. for example, as alveoli become smaller, water molecules come closer together, and surface tension is increased. As alveoli increase in size, water molecules are further apart, and surface tension is decreased.
  • Law of Laplace: The pressure required to keep an alveolus open is directly proportional to the surface tension within the alveolus and indirectly proportional to the alveolar radius. P = 2T/r, where P = pressure, T = surface tension, and r = radius.
  • Surfactant: A phospholipoprotein that contains both a hydrophilic and hydrophobic region that lines the alveoli. It adsorbs to the alveolar air–water interface and decreases surface tension by decreasing the interaction between water molecules. Thus, surfactants function to stabilize the alveoli; the tendency for small alveoli to collapse would result in emptying into larger alveoli.
  • Pleural pressure: Varies throughout the lung. At the apices, the pleural pressure is the most negative; therefore, the alveoli are more expanded than at the bases of the lungs.
• Gas exchange across the alveoli is determined by the partial pressure difference across the membrane and the solubility of the gas. The alveoli epithelium and basement membrane provide minimal hindrance and are optimal for this function. Carbon dioxide diffuses 20 times as rapidly as oxygen; oxygen diffuses twice as rapidly as nitrogen.

• Alveoli are the terminal branches in the pulmonary tree.
• The pulmonary tree begins with the trachea which then branches into the right and left mainstem bronchi. These bronchi then further divide into bronchioles, alveolar ducts, and alveolar sacs.
• The lungs receive blood from the pulmonary and bronchial circulation.
  • Pulmonary circulation: Deoxygenated blood flows from the right ventricles into the pulmonary arteries which branch along with the bronchial tree until they reach the respiratory bronchioles. At this point, they form a dense capillary network that provides a very large area for gas exchange. Oxygenated blood returns to the left atrium via the pulmonary veins.
  • Bronchial circulation: The blood is supplied from the aortic arch, the thoracic aorta, and the intercostals arteries. It feeds the trachea, bronchi, and bronchioles as well as the intrapulmonary nerves, ganglia, and interstitial lung tissue. It drains into the right atrium as deoxygenated blood.
• Zones: Blood flow through the lungs is dependent upon gravity as well as the relative pressures in each area. These pressures include the pulmonary artery pressure (Ppa), the pulmonary venous pressure (Ppv), and the alveolar pressure (PA). Three zones have been described:
  • Zone 1: Located at the lung apex, the perfusion pressure is about equal to the alveolar pressure so blood flow is low (PA > Ppa > Ppv). Zone 1 therefore has ventilation without perfusion and is essentially dead space.
  • Zone 2: The middle zone where the perfusion pressure is greater than the alveolar pressure so blood flows easily (Ppa > PA > Ppv). Zone 2 is the area of "best matched" ventilation and perfusion; it also contains the most number of alveoli.
  • Zone 3: Located at the lung base, where the perfusion pressure is much greater than the alveolar pressure so blood flow is high (Ppa > Ppv > PA). Zone 3 has very good perfusion, but less ventilation which results in shunting.

• Atelectasis is the term used to describe "collapsed" alveoli; the term can be applied to a single unit, lobe, or the entire right or left lung. Blood that perfuses the collapsed cannot pick up oxygen or offload carbon dioxide, resulting in pulmonary shunting. As the number of atelectatic units increases, it is less likely that the blood will be oxygenated by a proximal or distal unit before returning to the left atrium.
• Neonatal respiratory distress syndrome (RDS) can be present in premature infants due to a lack of surfactant. The increase in surface tension results in alveolar collapse (atelectasis), with resultant hypoxemia, decreased compliance, and problems re-inflating the lungs. Surfactant may be present by week 24 and is almost always present by gestational week 35. If there are mature levels of surfactant, the amniotic fluid will have a lecithin:sphingomyelin ratio >2:1. Corticosteroids may be given to encourage formation of surfactant in cases of pre-term labor.
• Emphysema is a disease where alveoli undergo destruction and elastic recoil is decreased; this results in increased alveolar size. It is most commonly caused by smoking, but can also result from alpha-1 antitrypsin deficiency. Bronchoalveolar lavage will demonstrate the presence of neutrophils; these cells cause damage to the lung parenchyma by secretion of proteolytic enzymes. Alveolar damage decreases gas exchange area, leading to hypoxemia, hypercarbia, and chronic dyspnea.
• Pulmonary fibrosis describes thickening of the alveolar wall; this impairs the diffusing capacity of gas through the alveoli.
• Cystic fibrosis is a genetic disease of the epithelial chloride channel to open normally in response to cyclic AMP. This defect decreases water passage across the epithelial membrane, leading to abnormally thick mucous in the airways. Mucus can obstruct small airways (plugs) and result in frequent pulmonary infections.
• Aspiration pneumonitis of acidic solutions may lead to destruction of surfactant-producing type II pneumocytes and the capillary endothelium. Damage to these cells may lead to atelectasis and leakage of fluid into the lungs. Arterial hypoxia may ensue, which leads to pulmonary vasoconstriction with associated pulmonary hypertension, as well as tachypnea and bronchospasm.
• Congestive heart failure describes cardiac dysfunction with "back-up" into the pulmonary vasculature (increased capillary pressure). This initially causes dilation and recruitment of pulmonary capillaries making it more difficult for alveoli to expand (results in decreased lung compliance, and increased work of breathing). As capillary pressures increase, fluid will eventually extravasate into the interstitial space around the alveoli. With further increases in pressure, fluid will eventually enter into the alveoli.
• Acute respiratory distress syndrome (ARDS) is defined as severe hypoxemia, diffuse shadows on CXR, low pulmonary compliance, and pulmonary edema not from left-sided heart failure. The lung parenchyma is severely damaged due to chemical mediators and fibroblasts. There is an inflow of protein-rich fluid into the alveoli due to increased permeability of the alveolar capillary membranes. Diseases that may precipitate ARDS include: septic shock, aspiration of gastric contents, pneumonia, pulmonary contusions, near drowning, severe trauma with associated shock, and inhalation of toxic gases or smoke.

Positive end-expiratory pressure (PEEP) is effective in improving arterial oxygenation and should be used when indicated. PEEP helps prevent alveolar collapse at the end of expiration and in doing so may decrease the shear stress associated with the opening and closing of alveoli with mechanical ventilation. PEEP also helps ventilation-to-perfusion matching as well as decreasing right-to-left intrapulmonary shunt. Because PEEP recruits alveoli that were previously collapsed, it helps to increase lung volumes and functional residual capacity (FRC). However, by increasing the intrathoracic pressure, it can decrease preload to the right atrium and decrease cardiac output.

Law of Laplace: P = 2T/r, where P = pressure, T = surface tension, and r = radius

• Atelectasis
• Surfactant
• Pulmonary Ventilation and Perfusion Matching
• Acute Respiratory Distress Syndrome
• Cardiogenic Pulmonary Edema
• Noncardiogenic Pulmonary Edema

Megan Freestone-Bernd , MD

Mary E. McAlevy , MD