The build-up of pulmonary edema

The abnormal accumulation of extravascular fluid, pulmonary edema settles in the lung interstitium and alveoli. There, it causes chaos, said cardiologist Gordon Peddle, VMD, DACVIM, who spoke at the 2025 Unique Seminar Destinations Annual Winter Seminar.¹

Affected animals can experience ventilation-perfusion mismatch, hypoxemia, impaired lung tissue compliance, respiratory fatigue and even death. Clinical signs include coughing, dyspnea, cyanosis, frothy oronasal exudate and collapse.

Photo: iwavephoto/Adobe Stock

Alveolar-capillary membrane

Ground zero for pulmonary edema, Peddle said, is the alveolar-capillary membrane. This vital partition allows gas exchange between the capillaries and alveoli, while shielding these vulnerable air sacs from fluid incursion. Pulmonary edema occurs when fluid leaks through the capillary endothelium to enter the interstitial space, and ultimately breaches adjacent alveoli.²

Mechanisms of pulmonary edema

Alveolar-capillary barrier damage

The alveolar-capillary wall holding back the waters can be directly defaced by pneumonia, contusions, emboli, toxins and drowning.³ But indirect inflammatory forces like sepsisand ischemia may also harm it. All low-pressure mechanisms, these alter membrane permeability.²

Imbalance of Starling forces

Fluid movement across the semipermeable vessel walls is regulated by “Starling forces” that result from the interplay between hydrostatic and colloid osmotic pressures.² “There’s a pretty decent balance at all times,” Peddle said.

Elevated pulmonary arterial load or passive rises in pulmonary venous pressures associated with congestive heart failure (CHF) can disrupt this delicate balance, as can dropping plasma oncotic pressure or increased negativity of pulmonary interstitial pressure.²

Lymphatic insufficiency

The lymphatic system plays a crucial role in fluid balance by utilizing oncotic pressures to draw excess fluid from the interstitium. In this way, the lymphatics help prevent alveolar flooding.²

Idiopathic causes

There are several types of pulmonary edema whose mechanisms are poorly understood, including neurogenic, post-anesthesia and high-altitude pulmonary edema.²

Pathophysiology of fluid exchange and pulmonary edema

Whatever the inciting cause, pulmonary edema results from disruptions in complex forces that govern fluid exchange in the lungs.² When the difference between capillary and interstitial hydrostatic pressure on the arterial side (flow) exceeds the difference between capillary and interstitial colloid osmotic pressure (protective clearance), fluid flows into the interstitium, and then breaches the alveoli.

Cardiogenic pulmonary edema

Pressure chambers typically come with safety valves. The lungs are no different: when left atrial pressure mounts, ensuing pulmonary hypertension is met with compensatory blood redistribution via capillary distension and recruitment.²

But pulmonary capillary pressure gauges are set to 8-12 mmHg. Once left atrial pressure brims above the threshold of 23-28 mmHg, Peddle explained, cardiogenic pulmonary edema starts to build in three phases.⁴ In the first, edema formation prompts recruitment and hypertrophy of lymphatic vessels, which pull out fluid and thereby maintain normal interstitial volume.

In the second—acute—stage, which lasts about 4 hours, left atrial pressures continue to climb and interstitial filtration level peaks. Lymphatic drainage rises slowly and glycosaminoglycans present in the extracellular matrix of the lungs allow the interstitium to soak up some expansion in fluid without alveolar flooding.

Stage 3 occurs once the volume capacity of the interstitial space is exceeded. The alveolar epithelial junction separates at the cellular level, and fluid washes into the alveoli in all-or-none fashion within each unit. (Neighboring alveolar chambers that have not been ruptured show minimal reduction in respiratory gas exchange).

“The dog is like a glass of water.And it’s filling up and then spilling onto the table,” Peddle said. “That’s pulmonary edema.”

Additionally, chronic surges in pulmonary capillary pressure lead to structural changes in lung parenchyma and vasculature.⁴ This remolding consists of alveolar and vascular fibrosis, causing irreversible lung and pulmonary artery disease. The pulmonary vein thickens, and lymphatic dilatation occurs. All these changes contribute to the development of pulmonary hypertension and, eventually, right-sided CHF (cor pulmonale).

Built-in “wet vacs”, pneumocyte channels within the alveoli upregulate to clear pulmonary edema.⁴ Once siphoned from the air sacs, fluid must be drained from the interstitium.This is accomplished by small, contractile lymphatic vessels that utilize intraluminal valves to move fluid out of the interstitial space toward the lymph nodes. Lymphatic flow can escalate several-fold before getting overwhelmed.

Cardiogenic pulmonary edema is diagnosed by history, physical exam and radiographic evidence of pulmonary edema affecting mainly the perihilar fields, or the lung fields diffusely.⁴

Treatment aims to improve cardiac performance, expand vascular capacity and lower intravascular volume. Beta agonists can be employed to directly clear alveolar fluid.Diuretics, like furosemide, boost urine output to lower intravascular volume, and sometimes trigger rapid pulmonary vasodilatation.⁴

While reducing further alveolar flooding, diuretics do not directly siphonalveolar fluid; for this reason, rapid administration of high doses of diuretics alone—compared to standard dosing—does not significantly clear edema and relieve dyspnea in dogs and cats with CHF. Ancillary therapies must usually be added to the mix.

Noncardiogenic pulmonary edema (NCPE)

Low-pressure NCPE, or permeability edema, results from lung injury that disrupts endothelial integrity.² One potential cause is airway obstruction. This can arise through brachycephalic disease, strangulation, laryngeal pathology, respiratory collapse, or an airway mass or foreign body.⁵

“Picture the golden retriever that plugs his airway with a tennis ball while playing outside,” Peddle said.

Whatever the airway jam, the result is falling negative intrathoracic pressure, hypoxia-induced microlesions in the alveolar-capillary unit, increased sympathetic tone and hikes in hydrostatic pressure.

Another brand of NCPE is neurogenic edema, likely linked to vasoconstrictive and hypertensive changes wrought by central nervous system insults. These include head trauma, hemorrhage, seizures and electrocution.

Lastly, NCPE can be the indirect fallout of damage by systemic disease or direct lung injury from smoke, toxins or excessive heat, all of which produce inflammation. Water aspiration that occurs in near-drowning traumatizes the alveolar-capillary border directly, and also produces barotrauma from forceful ventilation.³

Unlike cardiogenic pulmonary edema, which happens in stages, NCPE rushes in. The acute nature of most types of lung injury, and the wide-reaching damage they incur, leads to rapid alveolar flooding that can manifest as acute respiratory distress syndrome.

Dogs and cats suffering NCPE typically present hypoxemic and hyperglycemic.⁵According to published data, imaging shows interstitial/mixed interstitial-alveolar pulmonary pattern, favoring symmetric (77%), peripheral (92%) and dorsal (58%) distribution; asymmetric pattern is typically post-obstructive.^5,6

Takeaway

There exists no therapy to lessen pulmonary capillary hyperpermeability. Clinical management focuses on addressing the underlying etiology, providing respiratory support and allowing time to heal. Conservative administration of fluids and diuretics may be used effectively.⁷ Overall NCPE survival rates have been reported at 65-68%.⁵

References

1. Peddle G. Taking on water: the pathophysiology of pulmonary edema. Presented at Unique Seminar Destinations; Cancun, Mexico. February 8-15, 2025.
2. Murray JF. Pulmonary edema: pathophysiology and diagnosis. Int J Tuberc Lung Dis. 2011;15(2):155-160.
3. Joost JL, Bierens M, Lunetta P et al. Physiology of drowning: a review. Physiol.2016; 31:147-166. doi:10.1152/physiol.00002.2015
4. Ingbar DH. Cardiogenic pulmonary edema: mechanisms and treatment–an intensivist’s view. Curr Opin Crit Care.2019;25:371-378. doi:10.1097/MCC.0000000000000626
5. Drobatz KJ, Saunders M, Pugh CR et al. Noncardiogenic pulmonary edema in dogs and cats: 26 cases (1987-1993). J Am Vet Med Assoc.1995;206:1732-1736.
6. Bouyssou S, Specchi S, Desquilbet L et al. Radiographic appearance of presumed noncardiogenic pulmonary edema and correlation with the underlying cause in dogs and cats. Vet Radiol Ultrasound. 2017;58(3):259-265. doi:10.1111/vru.12468
7. Ali J, Chernicki W, Wood LD. Effect of furosemide in canine low-pressure pulmonary edema. J Clin Invest. 1979;64(5):1494-1504. doi:10.1172/JCI109608