Examples of Morphologic Types of Pneumonia in Domestic Animals

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1 Tutorial Module 5 Examples of Morphologic Types of Pneumonia in Domestic Animals Alfonso López Atlantic Veterinary College University of Prince Edward Island Canada 2014 Sept 24, 2014b

2 Examples of Diseases that Cause Bronchopneumonia in Domestic Animals Suppurative Bronchopneumonia Fibrinous Bronchopneumonia

3 Enzootic Pneumonia of Calves Enzootic Pneumonia is a clinico-epidemiological term that corresponds with a sub-acute to chronic suppurative bronchopneumonia in young calves. Enzootic Pneumonia is a multifactorial disease predisposed by environmental factors (temperature, humidity, poor air circulation, crowding), stress, immune status, viral infections (PI-3, Adenovirus, IBR, BRSV, etc.). Bacteria such as Pasteurella multocida (A, D), Hemophilus somnus, Actinobacillus pyogenes, Mycoplasmas (M. bovis, M. dispar) are often isolated from the lung. Hhigh morbidity but low mortality since the pneumonic process often involves only a small portion of the lung. Neonatal diarrhea can also predispose calves to Enzootic pneumonia as dehydration presumably impairs the respiratory defense mechanisms.

4 Enzootic Pneumonia of Calves The classic lesion in Enzootic Pneumonia is a suppurative bronchopneumonia in which purulent exudate can be expressed from the bronchi (arrow).. Microbiology is not always rewarding. Sometimes the viral infection that predisposed to pneumonia is long gone. It is imperative for control to eliminate excessive crowding, poor ventilation, changes in temperature, etc. Texture of an affected lung is firmer than normal with exudate in airways.. Note the cranioventral consolidation of lungs. In this particular calf, the pneumonic lesion were extensive enough to cause death.

5 Enzootic Pneumonia of Calves This was an incidental finding. Note consolidation only affecting 10% of the lung parenchyma (arrow) Although the distribution of lung lesions in Enzootic pneumonia of calves is cranioventral, the magnitude of lung involvement can vary considerably. It is considered that over 60% of lung parenchyma needs to be involved to incriminate suppurative bronchopneumonia as the cause of death. Cut section showing purulent exudate (arrow). The mucoid suggests chronicity (goblet cell hyperplasia).

6 Sequels to Enzootic Pneumonia Bronchiectasis Abscesses Pleural adhesions Dilated bronchi (ruptured walls) filled with mucopurulent exudate Pleural adhesions Abscesses affecting in cranioventral lung

7 Shipping Fever Bovine Pneumonic Mannheimiosis (Shipping Fever) is the number one cause of feedlot mortality in North America. Shipping Fever is caused by Mannheimia (Pasteurella) haemolytica A1 a commensal bacterium present in the bovine nasal flora that is effectively destroyed by the defense mechanisms. When this defense mechanisms are compromised by viral infections (PI-3, BHV-1, BRSV viruses) or stress, inhaled M. haemolytica colonizes the lung and causes severe fibrinous bronchopneumonia. BRSV, PI-3 and IBR Stress Dehydration M. haemolytica A1 produces a powerful cytotoxin that kills ruminant leukocytes and ffurther compromises the defense mechanisms.

8 Lung Rib cage Lungs from a steer that died acutely with respiratory signs. Note a thick layer of fibrin over the lungs and parietal pleura on the rib cage. Fibrinous implies severe damage to pulmonary tissue with fibrinogen leakage into the alveoli and pleura. Shipping fever is typical example of fibrinous bronchopneumonia. Yellow fluid is typically present in the thoracic of cattle dying with Shipping Fever (asterisk).

9 Note the cranioventral lung covered with a thick layer of fibrin. Consolidation involves over 60% of the total lung parenchyma. Affected lung has a hard texture on palpation. Shipping Fever Consolidated lung in Shipping Fever typically yields pure cultures of M. haemolytica. In outbreaks of Shipping Fever, it is important to determine the primary cause that render the lungs susceptible to M. haemolytica. Viral vaccination and good management practices aimed in reducing stress have a beneficial effect on the overall incidence of this disease. Shipping fever should not be confused with Hemorrhagic Septicemia which is a devastating disease in Africa and Asia caused by Pasteurella multocida serotypes B and E. Hemorrhagic Septicemia does not occur in the Americas.

10 Shipping Fever Typical marbled (mosaic) appearance of lung on cut surface Shipping Fever (Lung cut surface) Shipping Fever Some types of bacteria causing fibrinous bronchopneumonia such as Mannheimia haemolytica A1 produce powerful toxins that induce lung necrosis and irregular areas of cuagulative necrosis. There is also thrombosis of the lymphatic vessels causing notable distention of the interlobular. These two changes give the affected lung a mosaic or marbled appearance. Distended interlobular septa (arrows) and areas of coagulation necrosis (asterisks)

11 Bovine Histophilosis Complex (Histophilus somni) Septicemia (TME) Reproductive (infertility)* Heart (myocarditis) Ear (otitis) RESPIRATORY Suppurative bronchopneumonia Fibrinous bronchopneumonia

12 1 Respiratory Histophilosis Respiratory hemophilosis can cause both: 1. Suppurative bronchopneumonia as part of the Enzootic pneumonia 2. Fibrinous bronchopneumonia similar to Shipping Fever. 2 Histophilus somni is part of the normal vaginal flora. H. somni can also cause brain lesions as in Thrombotic Meningoencephalitis (TME), otitis, myocarditis, endometritis and abortion. Lung lesions caused by H. somni can t be easily differentiated from those caused by M. haemolytica.

13 Mycoplasma bovis Pneumonia Grossly, the pneumonic lung shows characteristic lumpy areas of caseous necrosis that resemble but are not true abscesses. I know what you are thinking: How on earth could I know if a bronchopneumonia is Caseonecrotic nodules caused by Mycoplasma bovis, Pasteurella multocida, Histophilus somni. Is this going to be asked in the exam? Well, not really. Why? Because it is not possible by gross examination alone to determine the precise etiology of a bovine bronchopneumonia. That is precisely why we always send lung samples to the diagnostic laboratory.

14 Ovine Enzootic Pneumonia Clinical term / Suppurative bronchopneumonia Multifactorial etiology: PI-3, RSV, Adenovirus, M. haemolytica, Mycoplasmas Farm environment Source unknown Immune status High morbidity Low mortality BALT hyperplasia Note cranioventral consolidation affecting around 15% of lung parenchyma. Chronic, locally extensive suppurative bronchopneumonia

15 Ovine Mannhemiosis (Mannheimia haemolytica) Pneumonic Septicemic M. haemolytica biotype A Similar pathogenesis to Shipping fever in cattle PI-3, RSV, Adenovirus, Chlamydia Stress The port of entry is aerogenous Fibrinous bronchopneumonia M. haemolytica biotype T (Biberstenia haemolytica) Stress Fulminating Sepsis DIC Hemorrhages, edema

16 Ovine Pneumonia (Mannheimia haemolytica) Note cranioventral consolidation of lung involving 30-40% of lung parenchyma. There are some tags of fibrin on the pleural surface. It is no wonder why some people use the term hepatization to describe the fibrinous consolidation Subcute, locally extensive fibrinous bronchopneumonia of a lung. You probably agree that the consolidated lung here looks pretty much like liver tissue (arrow). Ovine Mannheimiosis is similar to Bovine Shipping Fever where M. hamemolytica colonize the lung after the pulmonary defense mechanisms have been impaired by stress, viral infections, etc.

17 Porcine Enzootic Pneumonia Clinical term Suppurative bronchopneumonia Mycoplasma hyopneumoniae (primary pathogen) Predisposing factors: crowding, excessive ammonia, temperature, stress High morbidity but low mortality Secondary infections: P. multocida Archanobacterium pyogenes Mycoplasma hyorrhinis Affected pigs show slow growth The severity of lesions vary considerable

18 Porcine Enzootic Pneumonia Porcine Enzootic pneumonia is caused by Mycoplasma hyopneumoniae and infection is exacerbated by environmental factors such as humidity, temperature, crowding, and stress. The immune status of piglets also plays a significant role in the occurrence and severity of disease. The severity of lung lesions in Mycoplasma hyopneumoniae infection is further exacerbated by Pasteurella multocida, Haemophilus suis, Archanobacterium pyogenes and other less pathogenic mycoplasmas.

19 Porcine Enzootic Pneumonia Chronic, suppurative bronchopneumonia Note cranioventral consolidation of the lung involving 40% of the lung parenchyma. Bacteriology: Mycoplasma hyopneumoniae is a rather fastidious organism, difficult to grow and only a few laboratories are capable of isolation.

20 Porcine Pleuropneumonia Actinobacillus pleuropneumoniae Primary pathogen High mortality in naïve farms Fibrinous bronchopneumonia Cranioventral or Dorsocaudal Coagulative necrosis in lung Sepsis, shock, lung sequestrum

21 Porcine Pleuropneumonia Actinobacillus pleuropneumoniae is a primary pathogen and can cause pneumonia without other co-factors such as a viral infection or stress. The port of entry for A. pleuropneumoniae is aerogenous. In acute cases, it appears as a sudden death and affected pigs show hemorrhagic fluid oozing from the nostrils (arrows). The fundamental lesion in porcine pleuropneumonia is a fibrinous bronchopneumonia IMPORTANT NOTE This disease is the exception to the rule. Fibrinous consolidation is not always cranioventral in porcine pleuropneumonia.

22 Porcine Pleuropneumonia Note a single large, unilateral, focal lesion in the caudal diaphragmatic lung lobe (blue arrow). Actinobacillus pleuropneumoniae frequently produces large "lumps" in the lung as seen in this picture. These focal pneumonic lesions can become a large sequestrum.

23 Aspiration Pneumonia / Dog Suppurative bronchopneumonia in a puppy that aspirated vomit because of parvovirus infection Food aspiration occurs in all species but monogastric animals tend to die acutely because of acid ph of the stomach contents. Polygastric animals often survive Cranioventral consolidation and develop chronic pneumonia. Aspiration typically results in a bronchopneumonia but is not always bilateral or symmetrical, particularly if aspiration occurs during recumbence or surgery. The lesions, depending on severity and composition of aspirated material, vary from suppurative to fibrinous to gangrenous. Aspiration pneumonia also occurs in animals with neurological problems involving laryngeal muscles (e.g., rabies). Histology is required to confirm food particles in the lung.

24 Aspiration Pneumonia / Horse Horse died 24 hours after receiving a milk-shake prior to a race. Milk shake is a mixture of Gatorade, bicarbonate used to enhance athletic performance. Improper tubing lead to accidental intratracheal administration. Subcute, extensive fibrinous bronchopneumonia Note cranioventral consolidation affecting 60-70% of the lungs. A large portion of the cranial lobes are covered with a thick layer of fibrin (arrow). The entire lungs were also edematous hence the pleural rib imprints.

25 Aspiration Pneumonia / Cat Acute, locally extensive suppurative bronchopneumonia Lung of from a cat that shortly after recovering from anesthesia for elective spaying. Aspiration pneumonia is seen in animals with neurological disease that lead to swallowing problems. Unilateral cranioventral consolidation (C)

26 Puppy with parvovirus infection. Bronchopneumonia was suspected to be either the result of aspiration of vomit or secondary to impaired defense mechanisms caused by the immunosuppressive effect of virus (leucopoenia). C C Note cranioventral consolidation of the lung (C)

27 Enough of bronchopneumonia? Lets move to some examples of lung diseases characterized by interstitial pneumonia. Examples of Diseases that Cause Interstitial Pneumonia in Domestic Animals

28 Common Viral Infections Causing Interstitial Pneumonia in Domestic Animals in North America Cattle: Infectious Bovine Rhinotracheitis (IBR), Bovine Respiratory Syncytial Virus (BRSV) and Parainfluenza-3 virus. Small Ruminants: Ovine Adenovirus, Respiratory Syncytial Virus, Lymphoid Interstitial Pneumonia (Maedi), Caprine Arthritis Encephalitis (CAE). Horses: Equine Influenza, Equine Virus Rhinopneumonitis (EVR), Adenovirus, Equine Viral Arteritis. Pigs: Swine Influenza (SI), Porcine Circovirus-2 (PC-2), Porcine Respiratory and Reproductive Syndrome (PRRS). Dogs: Canine Distemper, Canine Parainfluenza, Canine Herpes. Cats: Feline Calicivirus, Feline Rhinotracheitis, Chlamydial infections (rickettsia).

29 Equine Influenza Subacute, diffuse, severe, interstitial pneumonia Viral infections are the most common cause of interstitial pneumonia in horses. Most common respiratory viral infections in horses are equine influenza, equine viral rhinopneumonitis and equine adenovirus. Diagnosis typically requires histopathology and viral detection i.e., virus isolation, PCR or immunohistochemistry. Note prominent rib imprints on lung surface. The texture of this lung was elastic and edematous.

30 Porcine Respiratory and Reproductive Syndrome (PRRS) Subacute, diffuse, severe, interstitial pneumonia. Note prominent rib imprints on lung surfaces. The lungs failed to collapse when the thorax was opened and the lung texture was notably elastic. PRRS, PC-2 and swine influenza are the most common etiologies in porcine interstitial pneumonia. Confirmation also requires of histopathology or viral detection in the diagnostic laboratory.

31 Porcine Respiratory and Reproductive Syndrome (PRRS) Acute, severe, diffuse, interstitial pneumonia. Note meaty and hyperemic appearance of the lung in a young piglet that died with respiratory signs. Lungs failed to collapse and costal imprints were evident on the visceral pleura. No exudate is present in the bronchi or pleura. Final diagnosis requires laboratory tests such as PCR, virus isolation or immunohistochemistry Immunoperoxidase showing positive staining for PPRS antigen in macrophages (arrow).

32 Canine Distemper Highly contagious disease of young Canidae (dogs, wolves, foxes, coyotes) caused by a Morbillivirus of the family paramyxoviridae. The clinical signs and lesions of distemper are multisystemic including conjunctivitis, rhinitis, interstitial pneumonia, enteritis, skin rash (abdomen), parakeratosis of skin (paws), and encephalitis. The CNS lesions are perhaps the most life threatening. Superimposed bacterial and protozoal (Toxoplasma gondii) infections of the lungs Mucopurulent conjunctivitis * are quite common in canine distemper.

33 Canine Distemper Hyperemia and discrete rib imprints typical of interstitial pneumonia. Lung lesions can be reversible; however, secondary infections by Bordetella bronchiseptica, Streptococcus spp., and E. coli can cause severe life-threatening secondary bronchopneumonia. Intracytoplasmic inclusion bodies in bronchial epithelium (arrows). H&E. Bar 10µm. Inclusion bodies in bronchial epithelium (arrows). Immunoperoxidase. Bar 10µm Some dogs survive the respiratory form of distemper but succumb to the encephalitic form of this disease. Vaccines are effective.

34 Feline Calicivirus Acute, multifocal vesicular glossitis. Feline Calicivirus affects domestic and wild Felidae. Note the two large vesicles on the tongue (arrows) Source unknown The most notable lesions include ulcerative stomatitis, glossitis (vesicles), conjunctivitis rhinitis and interstitial pneumonia. Exudate in conjunctiva and nostrils. Clinical signs and severity of lesions vary from subclinical to fatal depending on the Calicivirus.

35 Maedi / Ovine Progressive Pneumonia Ovine Progressive Pneumonia (OPP) also known as Lymphoid Interstitial Pneumonia (LIP) and Maedi. LIP is a retroviral disease of sheep in most countries, except Australia and New Zealand. The etiology is a. Transmission presumably occurs through infected colostrum. Like many other retroviral diseases, LIP is characterized by progressive emaciation and dyspnea. Histologically, alveolar walls are markedly Note rib imprints (arrow and pale lungs thickened due to infiltration of lymphocytes.

36 Maedi / Ovine Progressive Pneumonia Note thick alveolar walls due to extensive infiltration of lymphocytes

37 Interstitial Pneumonia is also caused by Allergic or Chemical Toxic Damage to the Air Blood Barrier

38 Atypical Interstitial Pneumonia in Cattle Atypical Interstitial Pneumonia is an obsolete but still used term. What used to be atypical is now typical. The so-called "atypical interstitial pneumonia" comprises several conditions characterized grossly by diffuse interstitial pneumonia: 1. Extrinsic allergic alveolitis (hypersensitivity pneumonitis or farmer's lung) is caused by inhalation anf hypersensitivity to fungal spores Saccharopolyspora (Micropolyspora) faeni 2. Bovine Pulmonary Edema and Emphysema (BPEE; fog fever). Ingestion of pasture (foggage) containing large amounts of L-tryptophan 3. Reinfection syndrome. Hypersensitivity reaction to reinfection with larvae of Dictyocaulus viviparus or to BRSV virus. 4. Other respiratory syndromes with interstitial pneumonia. Milk allergy (type I hypersensitivity in dairy cows), pit (manure) gases (H 2 S); "silo filler disease" (NO 2 ), etc.

39 Extrinsic Allergic Alveolitis in Cattle and Horses Moldy hay Inhalation of fungal spores (thermophilic actinomycetes) from moldy hay Saccharopolyspora rectivirgula (Microspolyspora faeni) Antibody response circulating antibodies Formation and deposition Ab-Ag complex in air-blood barrier Activation of Complement (C ) PMN-mediated injury to type I pneumocytes Cell mediated hypersensitivity Interstitial pneumonia

40 Extrinsic Allergic Alveolitis / Cow Lung parenchyma appears "meaty" with distention of interlobular septa due to the edema (arrows). Based on gross and microscopic findings, these lungs were diagnosed with an interstitial pneumonia compatible with extrinsic allergic alveolitis. Chronic, severe, interstitial pneumonia Confirmation of the diagnosis required serology showing high titers for Sacharopolyspora rectivirgula

41 Bovine Pulmonary Edema and Emphysema (Fog Fever) This form of "atypical interstitial pneumonia" 2-3 weeks after cattle have been put on pasture (foggage) containing large amounts of L-tryptophan.

42 Bovine Pulmonary Edema and Emphysema (Fog Fever) 1 Tryptophan Experimentally reproduced by injections of 3M-I. 3 methyl indole (3 MI) in blood to Club cell Tryptophan 3 methyl indole (3 MI) in rumen

43 Bovine Pulmonary Edema and Emphysema (Fog Fever) When the thorax is opened the lungs fail to collapse. Costal imprints are found on the pleural surface. The lungs are typically edematous and emphysematous (crepitous).. Detection of 3-MI is not routinely done and diagnosis always requires histopathology and a good clinical history and field investigation to the fame having respiratory distress days after exposure to lush pasture. Source unknown Note an edema characterized by distention of interlobular septa (arrows) and some bubbles of gas (asterisks).

44 Examples of Diseases that Cause Granulomatous Pneumonia in Domestic Animals

45 Bovine Tuberculosis Chronic, severe, multifocal granulomatous pneumonia Tuberculosis is a systemic disease that can affects many tissuees such as lungs, intestines, bones, bone marrow, gonads, kidneys, meninges, etc. Mycobacterium tuberculosis generally affects humans, but cross infections with M. bovis and M. avium could also occur. The texture of granulomatous pneumonia is nodular and on cut surface, granulomas may be calcified or have a tumoral appearance.

46 Equine Tuberculosis Chronic, severe, multifocal granulomatous pneumonia. Note numerous focal to coalescing granulomas in lung parenchyma. In horses tuberculosis appears like sarcomatous (tumor-like) lesions rather that the typical mineralized caseous granulomas seen in cattle. Histopathology and special stain (Acid fast) or bacteriologic culture are required for confirmation.

47 Granulomatous Pneumonia Histopathology / Granuloma M Typical granuloma is formed by a necrotic center (star) surrounded by a rim of epithelia macrophages (M) and finally an external band of fibrous connective tissue ( ) infiltrated by lymphocytes and plasma cells (not seen at this magnification). In most granulomatous pneumonias, the etiologic agent can be detected with special stains. Acid-fast bacilli (red) in affected tissue.

48 Rhodococcus equi Pneumonia World wide distribution caused by a telluric organism. Rhodococcus equi Infection in foals has three important presentations: 1- Respiratory 2- Intestinal 3- Skeletal The respiratory form is characterized by a chronic cough and weight loss. Note several large white nodules (asterisks) in the lung of this horse. The nodules are hard in texture and on a cut surface reveal a caseous appearance (See next slide). Chronic, severe, locally extensive, pyogranulomatous bronchopneumonia

49 Equine lung on cut surface. Rhodococcus equi Pneumonia Note large, granulomatous, ceseous (cheese-like) nodules. Microscopically, granulomas show macrophages containing gram-positive coccobacilli. The final diagnosis is made by culturing Rhodococcus equi. Chronic, severe, locally extensive, pyogranulomatous bronchopneumonia Rhodococcus equi has recently been reported in men and women with HIV infection. Please be very cautious with this serious and fatal disease. If abstinence is not desired, do not play Russian roulettepractice safe sex.

50 Systemic Mycosis Blastomyces dermatitides Cryptococcus neoformans Coccidiodes immitis Histoplasma capsulatum Histoplasmosis Blastomycosis

51 Granulomatous Pneumonia / Canine Blastomycosis Granulomatous pneumonia, severe, multifocal Gross: Note small nodules in all areas of the lung. These lesions are typical of granulomatous pneumonia. Sometimes histopathology is required to differentiate granulomatous pneumonia from neoplastic nodules in the lung. Histopathology: Giant cell containing several PAS-positive Blastomyces dermatitides (arrows).

52 Feline Infectious Peritonitis (FIP) Distended abdomen; Ascites Multifocal, granulomatous peritonitis In both wet and dry forms of FIP, pyogranulomas are typically present in most internal organs. Cats with strong cell-mediated immunity suffer only a transient infection. Cats with partial cellmediated immunity develop the dry-form and the cats with poor cell-mediated immunity develop the most severe, wet-form of FIP. There is still much to learn about the pathogenesis of FIP.

53 FIP / Granulomatous Pneumonia and Hepatitis Note many granulomas in the lung (arrows) and in the liver (arrowheads)

54 Granulomatous Pneumonia / Mullerius capillaria / Ovine Multifocal, chronic, severe, granulomatous pneumonia Numerous, sub-pleural granulomas distributed throughout the lungs (black arrows). This common parasitic disease of sheep and goats requires an intermediate host (snail). Nodules become hard (calcified) and microscopically the lung lesions show parasitic larvae and eggs. Abundant parasitic larvae in the lung

55 Some images were acquired from veterinary colleges of Canada, United States and Mexico and the names of pathologists who contributed with some slides are known. Their valuable contribution is sincerely acknowledged. I would like to thank Dr. María Forzán, Atlantic Veterinary College, for critically reviewing these modules.

56 Tutorial 5 If you have any comments, criticisms or suggestions about these tutorial modules please let me know. Also, if you find any errors or typos please let me know too lopez@upei.ca

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