All pressures mentioned to this point have been hydrostatic, whether alveolar, vascular, or intrapleural. Hydrostatic pressures within blood vessels are only partially opposed by interstitial hydrostatic pressure of the delicate alveolar parenchyma. This imbalance would rapidly move blood water out of the vascular spaces by ultrafiltration, if capillary hydrostatic pressures were not opposed by colloid osmotic pressure exerted by blood proteins (Fig. 7.5). Formally presented, Starling’s law of the capillary states that:
Blood fluids tend to extravasate, that is, leave a capillary at its arterial end to form lymph. Most lymph returns to the capillary by reabsorption at its venous end. Net fluid loss is normal and collects in adjacent lymphatics. Extravasation that exceeds lymphatic capacity to remove it causes edema. From Fox, Human Physiology, 10th ed.; 2008.
The hydrostatic pressure PMV within the blood vessel causing fluid to extravasate from lung capillaries into the septal interstitium is mostly unopposed by any rise in PPMV, because the delicate alveolar epithelial membranes cannot resist increases in interstitial volume as can occur systemically in tissues like skeletal muscle. Rather, the septal interstitial compartment expands with this capillary ultrafiltrate that drains into blind-ended pulmonary lymphatic capillaries. However, if lymphatic drainage cannot remove the ultrafiltrate at a sufficient rate, interstitial edema will occur that can progress to alveolar edema accompanied by disruption of epithelial layers (Fig. 7.6). Maximal lung lymphatic drainage is probably 2-3 times the normal flow rate of 20 mL/h.
(a) Peripheral alveoli are filled with acellular ultrafiltrate in this specimen of endotoxemic lung tissue. (b) Neutrophil-rich edema and alveolar exudates in a rat with gram-negative pneumonia.
The protein colloid osmotic pressure πMV of blood in the alveolar capillaries is relatively constant as in systemic capillaries, except in diseases like Kwashiorkor or liver failure that reduce plasma [albumin]. Likewise, πPMV is generally considered constant unless interstitial [protein] declines by dilution with water from the blood (ie, ongoing edema) or from within the airspaces (eg, near-drowning in fresh water). Smoke or fume inhalation, aspiration of stomach contents or toxic chemicals, and blood-borne diseases like gram-negative endotoxemia alter the endothelial K or σ such that net fluid flow out of alveolar capillaries increases and edema occurs, even if PMV, PPMV, πMV, and πPMV are all normal.
In practice, factors in Starling’s equation are most likely to become unbalanced in two main ways to initiate interstitial and then often alveolar edema. The first occurs when PMV becomes elevated due to systemic hypertension, generally rising in parallel with increases in PPA and PPV. The resulting leak is termed cardiogenic edema since its cause is usually congestive heart failure or mitral valve dysfunction (Table 7.1). In this type of edema, the endothelial barrier to protein movement is usually intact (ie, K and σ are normal), and the resulting edema fluid has a [protein] lower than that of plasma.
Table 7.1Primary categories of pulmonary edema ||Download (.pdf) Table 7.1 Primary categories of pulmonary edema
|Feature ||Cardiogenic ||Noncardiogenic |
|Most common etiologies ||Left heart failure, mitral stenosis ||ALI, ARDS* |
|Lung capillary pressure PMV ||Increased ||Normal |
|Lung capillary K and σ ||Normal ||Increased |
|[Protein] of edema fluid ||<< plasma [protein] ||< or = plasma [protein] |
The second major type of pulmonary edema occurs despite normal hydrostatic forces and is considered noncardiogenic in etiology. It commonly begins as an increased permeability (K and/or σ) of the capillary endothelial or alveolar epithelial layers, often following direct cellular injuries. Plasma proteins can now leak out directly between adjacent barrier cells, so that such edema fluids have a higher [protein]. Indeed in severe cases, intact formed blood elements can appear within the interstitial or alveolar spaces as well, yielding a hemorrhagic edema (Fig. 7.7). Such severe forms of edema are a characteristic feature of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS). How these disruptive changes in pulmonary endothelial or epithelial permeability occur in the previously healthy lung, and the impact they have on diffusional gas exchange will be discussed at length in Chap. 28.
Interstitial edema around airways and blood vessels (double-headed arrows) decreases their diameters and increases resistances to flow. Such edematous cuffs or sleeves also reduce traction that can be exerted by elastic elements in the parenchyma. (a) Rat lung 72 hours after induction of plague pneumonia by intratracheal instillation of Yersinia pestis; neutrophils predominate the interstitial infiltrate below a large artery. (b) Rat lung 24 hours after acute IV (intravenous) infection with Candida albicans; numerous erythrocytes in the interstitial space of the arteriole are typical of this often hemorrhagic edema.
CLINICAL CORRELATION 7.3
Pulmonary edema is conventionally viewed as an acute restrictive lung disease (Chap. 6) because fluids within the alveolar septa and distal airspaces reduce the functional parenchymal volume available for ventilation. However, such edema also has a propensity to accumulate within the interstitial spaces surrounding larger airways and blood vessels (Fig. 7.7). Such edematous cuffing creates a sleeve of fluid that prevents dilatation along the length of such vessels, even if smooth muscle cells within their walls are relaxed. The resulting bronchiolar edema is an acute obstructive lung disease that will adversely affect peak expiratory flow rates and increase dynamic airway resistance. Thus, a patient with ALI or ARDS would have a mixed respiratory disorder that clinically has both a complex etiology and an uncertain outcome (Chaps. 26 and 28).
The specific causes of pulmonary edema are multiple (Table 7.2), and a complete discussion is beyond the scope of this introduction to the topic. However, it is evident that perturbations to virtually all terms within Starling’s equation occur clinically, although not all result in cases of equal severity or duration. Of interest to the general public is the sudden and often unpredictable development of high altitude pulmonary edema, HAPE in some travelers to elevations above their normal residences. By poorly understood mechanisms, severe hypoxia reduces active Na+ transport that normally drives the reabsorption of capillary ultrafiltrate and thereby keeps alveolar membranes moist but free of excess fluid. This uncleared alveolar fluid, whose formation is invariably accelerated by the increased PPA and PMV that are also caused by hypoxia (Chap. 8), leads to acute HAPE in susceptible individuals. What makes some climbers sensitive to this serious side effect of even moderate altitude exposure, while their climbing partners may be unaffected, remains an intriguing and unsolved question in the field (Chap. 13). In any case, resolution of their often hemorrhagic edema is rapid and reversible if a descent to lower elevations can be achieved in time.
Table 7.2Causes of pulmonary edema sorted by Starling’s equation defect ||Download (.pdf) Table 7.2 Causes of pulmonary edema sorted by Starling’s equation defect
|Altered Parameter ||Diseases or Processes Affecting the Parameter |
|increased PMV ||congestive heart failure; mitral stenosis; myocardial infarct |
|increased PPMV ||reduced lymphatic drainage from lymphangitis or neoplasia |
|decreased PPMV ||alveolar overdistension (neurogenic or mechanical); hypoxia? |
|increased σ ||endotoxemia; sepsis; inhalation injury; drug toxicity; prolonged hyperoxia |
|decreased πMV ||hemodilution; hypoalbuminemia; Kwashiorkor |
|decreased πPMV ||near-drowning in fresh water; evolving interstitial edema; high altitude? |