JPC SYSTEMIC PATHOLOGY
Signalment (JPC #1460187): Rhesus macaque
HISTORY: This animal was used in an experimental pulmonary research study.
HISTOPATHOLOGIC DESCRIPTION: Lung: Multifocally, over 90% of alveolar septa, are expanded by eosinophilic homogenous edema fluid, eosinophilic fibrillar material (fibrin), fibrosis, and few neutrophils, macrophages, lymphocytes, and plasma cells. There is necrosis and loss of type I pneumocytes. Multifocally and strikingly, alveoli are lined by cuboidal epithelial cells (type II pneumocyte hyperplasia), which occasionally form micropapillary projections into alveolar lumina. Multifocally, alveolar lumina contain increased numbers of macrophages and fewer neutrophils mixed with edema, minimal hemorrhage, and fibrin. Multiple contiguous alveoli coalesce and are expanded by clear space (emphysema), or are consolideated (atelectasis). The bronchiolar epithelium is hyperplastic, piled up to 4 layers thick. There is multifocal anthracosilicosis and perivascular, peribronchiolar and pleural edema and fibrin exudation.
MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, interstitial, proliferative, subacute, diffuse, marked, with type II pneumocyte hyperplasia, alveolar emphysema and bronchiolar epithelial hyperplasia, Macaca mulatta, non-human primate.
ETIOLOGIC DIAGNOSIS: Pulmonary oxygen toxicosis
- Oxygen levels of 85-100% can lead to damage of capillary endothelium, type I pneumocytes, and serofibrinous exudation in alveoli or diffuse alveolar damage
- High partial pressure oxygen is toxic to the respiratory, cardiovascular, and
- digestive systems, with the lung being the most susceptible
- Oxygen is toxic to the lung in humans when FIO2 administered is >0.60 at 1 atmosphere of pressure for >24 hours
- Oxygen toxicity is one of many processes resulting in acute lung injury (ALI) and the resulting histopathology of diffuse alveolar damage (DAD)
- Diffuse alveolar damage has three phases:
- Acute exudative phase: Alveolar septa contain edema and are congested; infiltration by macrophages and neutrophils; and hyaline membranes
- Subacute proliferative phase: Type II pneumocyte hyperplasia is evident by 2-3 days post-injury
- Chronic fibrosing phase: Fibroblast invasion of affected alveoli forming granulation tissue-like fibrous tissue that’s incorporated into the alveolar septa; ongoing damage within the septa result in TGF-β-induced fibroblast recruitment and well-organized interstitial fibrosis evident by day 14
- Increased partial pressure of inhaled oxygen causes increased free radical formation, overwhelming host defense mechanisms including superoxide dismutase, glutathione peroxidase, and catalase; bilirubin and vitamins C and E
- Reactive oxygen species (ROS) and free radicals (superoxide, hydrogen Oxygen toxicity preferentially damages endothelial cells and type I pneumocytes due to paucity of oxygen radical scavenging mechanisms in these cells; resistant type II pneumocytes proliferate
- peroxide, singlet oxygen, and hydroxyl radicals) cause cellular damage by lipid peroxidation, protein oxidation, and DNA strand breaks
- Influx of inflammatory cells, edema, activation of arachidonic acid cascade, and
- complement activation
- Protein-rich edema fluid and remnants of necrotic epithelial cells form hyaline
- Lung compliance decreases as surfactant levels decrease, causing atelectasis;
- fibrin organizes, resulting in interstitial fibrosis
TYPICAL CLINICAL FINDINGS:
- Initially, may be asymptomatic
- Can progress to tracheobronchial irritation (coughing and substernal pain); later severe pulmonary edema causes dyspnea, cyanosis, and death
TYPICAL GROSS FINDINGS:
- Lungs are diffusely heavy and edematous
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Acute lesions:
- Perivascular, interstitial, and intra-alveolar hemorrhage, edema, and fibrin
- Variable necrosis of pulmonary epithelium and type I pneumocytes
- Neutrophilic and histiocytic inflammation
- Hyaline membrane formation
- Chronic cases:
- Prominent type II pneumocyte hyperplasia with eventual organizing fibrosis
- Acute respiratory distress syndrome (ARDS; shock lung)
- Diffuse pulmonary infections
- Intoxications (ozone, paraquat, nitrogen dioxide)
- Domestic animals
- ARDS, caused by diffuse alveolar capillary damage, is characterized by rapid onset of dyspnea, tachypnea, tachycardia, cyanosis, and severe arterial hypoxia that is unresponsive to oxygen therapy, and progresses to multisystem organ failure
- Lab animals
- Neonatal rats, mice and rabbits are resistant to oxygen toxicity
- Adult rats have similar histological changes
- Pleural effusion is the hallmark of oxygen toxicity in the rat
- In rabbits there is reduced tracheal cilia concentration, discharge of goblet
- cell mucus, and slowed tracheal mucus velocity
- Often necrosis of CNS neurons, cardiac myocytes, and renal tubular epithelium
- Caswell JL, Williams KJ. Respiratory System. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 2. 6th ed. Philadelphia, PA: Elsevier; 2015:518.
- Husain AN. The lung. In: Kumar V, Abbas AK, Fausto N, Aster JC, eds. Robbins and Cotran Pathologic Basis of Disease. 8th ed. Philadelphia, PA: Elsevier Saunders; 2009:680-682.
- Lowenstine LJ, Osborn KG. Respiratory system diseases of nonhuman primates. In: Abee CR, Mansfield K, Tardiff S, Morris T, eds. Nonhuman Primates in Biomedical Research Volume 2: Diseases. 2nd ed. San Diego, CA: Academic Press; 2012:112-116.
- Mach WJ, Thimmesch AR, Pierce JT, Pierce JD. Consequences of hyperoxia and the toxicity of oxygen in the lung. Nurs Res Pract. 2011;Article ID 260482:7 pages.