PATHOLOGY OF

RESPIRATORY SYSTEM
Pathogenesis of respiratory system diseases
• Respiratory diseases are caused by a large number of infectious and non-
infectious agents.
• The formation of the lesion depends on the interaction between the
entrance route of the agent, its structure, density and the sensitivity of the
tissue to the agent.
• Among these, the entrance way of the agent is of great importance.
 Pathogenesis of respiratory system diseases
• Harmful substances taken through aerogen route often show their effects in the
airways.
• The nasal cavity and upper airways are often affected by irritants containing
particles, strong soluble gases, or infectious agents common in the upper
respiratory epithelium.
• The lower airways are affected by smaller particles, poorly soluble gases or
infectious agents with affinity for bronchiolar and alveolar epithelium.
Pathogenesis of respiratory system diseases
• Viruses generally have tropism to both terminal bronchiolar
epithelium and type II alveolar epithelial cells.
• Replication of viruses in these cells leads to the development of
the inflammatory reaction in the terminal bronchioles (airways)
and surrounding interalveolar septums, thus bronchointerstitial
pneumonia is formed.
Pathogenesis of respiratory system diseases
• Most of the lesions are diffuse, focal or disseminated multifocal in
hematogenous infections in the lung and are more affected by
alveolar septums and interstitial tissue, bronchi and bronchioles.
• Traumatic injury to the respiratory system is less common;
• It occurs as a result of the penetration of foreign bodies and the
spread of lesions from surrounding tissues and spaces directly or
through lymph vessels.
Pathogenesis of respiratory system diseases
• Disruption of respiratory system defense mechanisms: Factors causing this
deterioration are:
• 1- Viral infections: Bacterial pneumonia often develops after a viral infection.
Viruses that predispose to secondary bacterial infections include Bovine
Herpesvirus Type-1, RSV, Adenovirus, Distemper disease virus, BVD-MD
virus, and Parainfluenza-3. They disrupt the defense system by disrupting the
mucociliary system and reducing the phagocytosis ability of alveolar
macrophages, resulting in secondary bacterial pneumonia.
Pathogenesis of respiratory system diseases
• 2- Toxic gases: Toxic gases such as ammonia, which are abundant
in environments such as poorly ventilated barns, disrupt the lung
defense mechanisms.
• 3- Pulmonary edema and hypoxia: They act by impairing the
production of surfactants in type 2 pneumocytes and decrease in
phagocytic functions of alveolar macrophages.
Pathogenesis of respiratory system diseases
• 4- Dehydration: As the viscosity of mucus increases, mucociliary
activity decreases or stops.
• 5- Stress, hunger and cold: They cause a decrease in cellular and
humoral immunity and a decrease in mucociliary activity.
• 6- Immunodeficiency: Congenital or acquired immune deficiency
disorders.
 Pathogenesis of respiratory system diseases
• Summary of reactions caused by various microbial agents in the respiratory
system:
• Viruses are absolute intracellular agents and multiply inside the cell. As a
result, they cause degeneration, necrosis and sometimes hyperplasia in
epithelial cells.
• In addition, they form mononuclear cell infiltrations, lymphoid hyperplasia,
increase in interstitium and connective tissue, fusion formation and inclusion
bodies in epithelial cells.
Pathogenesis of respiratory system diseases
• Bacteria usually cause hyperemia, edema, degeneration and
desquamation of epithelial cells, especially an exudate consisting
of neutrophil leukocytes and signs of obstruction of the airways
by this exudate.
• Helminths cause proliferative-exudative changes. In the reaction
that occurs, eggs, larvae and adult forms of the parasite are seen
together with eosinophil leukocyte infiltrates.
 Nasal cavity and sinuses
• Epistaxis is a term commonly used for nosebleeds. It does not matter whether
the source of bleeding is the nasal cavity or sinuses. Bleeding can also be from
the nasopharynx or from deep parts of the respiratory system.
• Especially in horses, epistaxis, which is formed as a result of heavy exercise
and takes its origin from the lungs, is called post-exercise pulmonary
hemorrhage. In this case, a bloody foamy content is often seen in the noses of
sheep cadavers. This case is the result of terminal lung congestion, edema,
and bleeding.
 Nasal cavity and sinuses
• Diapedesis bleeding is seen in morbus maculosis, in some infectious diseases
(anthrax, swine fever, distemper, infectious anemia of horses), insect bites
and poisonings (mercury).
• Note: Morbus maculosus: Purpura hemorrhage in horses: It is characterized
by hemorrhagic diathesis (tendency to bleeding), peripheral edema,
neutrophilia, lymphopenia and thrombocytopenia. It occurs secondary to
endothelial damage during the removal of soluble immune complexes
following their accumulation in the circulation. It is mostly encountered in
horses during the course of infectious diseases of the respiratory system such
as strangles (gurm) and after recovery.
Gross appearance of ENA. Tumour mass fills the nasal cavity (arrows)
ENA
Histopathological appearance of the mixed type of ENA, H.E.
Immunolabeling of retrovirus-related antigen on the surface of secretory epithelial cells of the
ethmoid region (arrows). Streptavidin biotin method. Harris haematoxylin counterstain
 Rhinitis
• Rhinitis is inflammation of the mucous membrane of the nose.
• A microbial flora is normally found in the nasopharyngeal mucosa. This flora is formed by
the adhesion of bacteria to epithelial cell surfaces via adhesins. The function of normal flora
is to prevent the adherence and colonization of more virulent microorganisms, especially
gram-negative microorganisms, to the mucosa.
• A destruction of the mucosal surface can cause normal flora to acquire pathogenic activity,
or more importantly, it disrupts the surface attachment points of normal flora agents.
Therefore, adhesion and colonization of pathogenic agents becomes possible. Similar
changes are also encountered in systemic immunodeficiency or post-operative non-specific
conditions.
 Rhinitis
• Fungal infections or other opportunistic infections following prolonged antibiotic
therapy are related to this removal of normal bacterial flora.
• Reasons of primary injuries are usually viruses.
• Allergens are important mainly to cattle and less to cats, dogs and other species.
• Irritant volatile gases, dust and very dry air can sometimes cause damage to the
nasal cavity epithelium.
 Rhinitis
• Rhinitis can be acute or chronic depending on the course of the disease.
• Depending on the nature of the exudate, it can be classified as serous, catarrhal,
purulent, ulcerated, pseudomembranous, hemorrhagic or granulomatous.
• Pseudomembrane, ulcerative or hemorrhagic rhinitis is an indication of severe
destruction.
• Chronic rhinitis mostly manifests itself with proliferative changes (rhinitis
hypertrophicans), however, sometimes nasal concha atrophy is seen (rhinitis
atrophicans) especially in large dogs.
 Rhinitis
• Rhinitis seen in special diseases:
• Inclusion Body Rhinitis in Pigs
• Atrophic Rhinitis in Pigs
 Rhinitis
• In the serous stage at the beginning of viral, allergic or non-specific rhinitis, the
mucosa swells and becomes gray red due to hyperemia.
• Histologically, hydropic degeneration is observed in the epithelium and it is
noteworthy that these cells have lost their ciliums.
• There is hyperactivity in goblet cells and submucosal cells.
• Swelling in the mucous membranes clinically causes mild difficulty in breathing,
sneezing and sniffing.
 Rhinitis
• A few hours or days after the onset of the disease, serous
inflammation undergoes secondary bacterial infection and
secretion change.
• Hyperemia, edema and swelling increase.
• Runny nose becomes catarrhal or purulent. Severe ulceration is
seen in purulent rhinitis.
 Rhinitis
• Pseudomembranous (fibrinous) and fibrino-necrotic (diphtheria) rhinitis:
• Fibrino-necrotic inflammation is accompanied by severe bacterial infection and is
mostly dry yellowish in color, indicating Fusobacterium necrophorum infection.
• The criteria for distinguishing these two lesions are as follows:
• Fibrinous membranes are easily removed and there are no defects in the mucosa.
• The fibrino-necrotic membrane is difficult to remove, and when it is removed, red
ulcerated living tissue is seen underneath.
 Rhinitis
• Allergic rhinitis: Allergic rhinitis is inflammation of the inside of the nose caused by an allergen, such
as pollen, dust, mould, or flakes of skin. Sometimes it is observed sporadically in dogs, cats and
horses.
• It is a disease similar to hay fever in humans in clinical response to treatment.
• It is a type 1 hypersensitivity reaction to a large group of allergens.
• It is most commonly caused by plant pollen, fungi, dust and mites.
• It is characterized by an allergic reaction, pronounced mucosal edema, hyperemia, and increased
mucus secretion. This is accompanied by leukocytic infiltration with prominent eosinophils.
• Diagnosis is based on runny eyes and nose, sneezing, nose rubbing, head shaking, and perhaps
epistaxis. In addition, there are eosinophils in the exudate and lavage fluids in the nasal cavity.
 Rhinitis
• Mostly cattle and sometimes sheep have seasonal rhinitis. Its
clinicopathological features indicate an allergic pathogenesis. There are data
that sick cattle are allergic to pollen. Especially in the summer season, when
the vegetation on the pastures is revived, the disease occurs, either
individually or in flocks.
• There are runny nose, lacrimation and sneezing clinically. The nasal mucosa is
pale and swollen due to edema. Exudate is serous at first, then becomes
mucopurulent. Eosinophils are the main component found in the exudate.
 Strangles
(Lymphadenitis equorum, gurm)
• It is an acute and contagious disease, characterized by inflammation of the
upper respiratory tract of especially young horses and abscess of the regional
lymph nodes.
• The causative agent is Streptococcus equi, an obligate parasite in the upper
respiratory tract mucosa of equines.
• It is very resistant to external effects in exudate.
 Strangles
• The disease agent maintains its vitality in the barn for months. The source of
infection is animals that are porter but do not show any clinically significant signs of
disease.
• Strangles are more common among young horses. Those who are one or two years
old are more likely to get this disease. Keeping young horses in one place increases
the incidence of the disease.
• It is difficult to identify carrier horses because the disease agents are spaced in the
currents and the area of acquisition in a single animal varies between the nasal and
pharyngeal regions.
 Strangles

• The formation of the disease begins with the epithelial adhesion of the
agent in the soft palate and pharynx and its entry into the epithelial cells.
• There is intense chemotaxis of neutrophils to mucous and regional
lymph nodes. This intense chemotaxis is stimulated by factors that
develop from the alternative complement system. This system is
activated by peptidoglycans in the cell wall of the bacteria.
 Strangles
• Surface M protein (virulent anti-phagocytic factor found in
streptococci) and hyaluronic acid provide the resistance of the
agent to phagocytosis.
• All strains of the agent produce potent cytotoxins, which creates
the agent's resistance to intracellular digestion and causes rapid
degeneration of neutrophils.
 Strangles
• Approximately 70% of horses recovering from the strangles
become immune to the disease. Acquired resistance depends on
Ig A and Ig G produced locally in the nasopharynx.
• Serum of recovered or vaccinated horses contains Ig A and
bacterial M protein. These are responsible for the vasculitis that
underlies glomerulonephritis and combined purpura hemorrhage.
 Strangles
• In Strangles disease, the incubation period is 3-4 days. The disease begins with a rise in body
temperature, mild cough and bilateral nasal discharge. Serous nasal discharge becomes
catarrhal and purulent within a few days.
• In typical cases, inflammatory enlargement of the head and neck lymph nodes is seen.
Submandibular and retropharyngeal lymph nodes are affected initially and often severely.
• Acute inflammatory swelling is severe, but as liquefaction and pus develop, lymph nodes
become fluctuant.
• Lymph nodes open into the skin after a short time and the forming yellow, cream-like pus
flows out.
• Pus is not always seen in the lymph nodes, in this case, clinical diagnosis is quite difficult.
 Strangles
• In strangles, the lesion in the nasal cavity is a nonspecific purulent
rhinitis.
• The creamy form of purulent exudate collects in the folds of the
turbinata and causes temporary distortion in them.
• The nasal mucosa is hyperemic and edematous, sometimes small
mucosal ulcers are noticeable.
 Strangles
• In older horses, the disease is mild and causes catarrhal rhinitis and
pharyngitis. Most of the time, no abscess is formed in the lymph nodes.
• Although metastatic abscesses are found in the liver, kidneys, synovial
membranes and brain, the mediastinal and mesenteric lymph nodes are
mostly affected.
• Irritation may spread to serous membranes, causing purulent pleuritis
and peritonitis.
 Strangles
• Two other important consequences of this disease are
hemorrhagic purpura (Morbus maculosus) and enlarged
retropharyngeal lymph nodes. As a result of the pressure of these
growing lymph nodes on the nervus laryngeus recurrens, this
nerve is focally destroyed. This may cause the formation of
laryngeal paralysis, facial nerve paralysis or Horner Syndrome.
 Note
• Horner syndrome: Paralysis in the affected area of the eye, face
and head as a result of damage and paralysis of the cervical
sympathetic nerve fibers.
• It is a syndrome characterized by narrowing of the pupil,
vasodilation and usually the shrinkage of the eyeball in the orbit,
and the loss of functions of the head and face parts on the
affected side.
 Note
• Morbus maculosus = Purpura hemorrhagica: Diffuse hemorrhage
resulting from increased capillary permeability. Following the
accumulation of soluble immune complexes in the circulation, it
occurs secondary to endothelial damage during their removal. It is
mostly seen in horses during the course of diseases such as gurm
and after their recovery. It usually results in death.
 Glanders, Ruam, Malleus
• It is an infectious disease caused by a Gram (-) bacillus, Pseudomonas mallei
(Burkholderia mallei).
• The disease is characterized by purulent nasal discharge, nasal mucosal ulceration,
lung lesions, and ulcerating nodules along the subcutaneous lymphatics.
• Although it is a disease of equines, it can sometimes be seen in humans.
• Carnivores that eat the flesh of sick horses can also naturally catch the disease.
• Goats and sheep are susceptible to contact infection, but cattle and pigs are not.
 Glanders
• It is characterized by nodular lesions in the lungs; ulcerous and nodular lesions on the skin. Nodules under the
skin and skin in the lymphatic channels can become ulcerated over time and a sticky honey-like discharge occurs.
This form is called "farcy«.

• The causative agent is not resistant to external environmental conditions and the infection is caused by direct or
indirect transmission of the excretion and nasal discharge of the sick animal. It is also found in lesions on the
nasal mucosa and skin.

• In horses, the disease is usually chronic and most frequently settled in the respiratory system. The agent can be
excreted with feces, urine, saliva and tears.
 Glanders
• Chronic syndrome of glanders often involves nasal, lung, and skin forms. One of
these types is seen in every case of disease. However, sometimes three types can
coexist.
• There is usually a unilateral runny nose in rhinitis in the glanders, but the
inflammation may also be bilateral. Nasal discharge is abundant, thick, purulent
and greenish-yellow in color. It contains bloody and spilled epithelial fragments
in places.
 Glanders
• The agent usually enters the body by ingestion of contaminated feed and water, and
rarely by inhalation. The taken agent passes through the pharynx and intestinal
mucosa and reaches the lymph channels and lymph nodes and multiplies. It then
settles in the lungs, nose and skin through the blood.
• The agent that comes to the nose first causes destruction (endangitis) and
thrombosis in the vascular endothelium. It then goes out of the vein and causes
periangitis. As a result of the developing inflammatory reaction, nodular glandular
lesions occur.
 Glanders
• Microscopically, hyperemia, inflamed thrombosis, edema and bleeding
are observed in the vessels in the nasal mucosa. In the submucosa, there
are neutrophils and the caseonecrotic center and surrounding nodules
consisting of histiocytes, epithelioid cells, lymphocytes, and sometimes
giant cells.
• Severe exudative cases are typically necrotic centered, and in these cases,
karyorrhexis is observed in neutrophils in the center as a result of pus
and liquefaction, and this finding is quite typical for glanders.
 Glanders
• The typical lesion in the lung is nodule, but severe diffuse pneumonia may be
present in some acute cases.
• Nodules spread to the entire lung in a miliary fashion, but they can be seen better
under the pleura.
• These are basically pyogranulomatous nodules. Due to dystrophic calcification, the
centers of these lesions may be sandy.
• There are very few glandular lesions in the digestive system.
 Glanders
• Subcutaneous lymph vessels in the skin gland known as farsi
(farcy) tubes in horses are thickened in the form of cords.
• Nodules that are prone to ulceration line up along thickened
lymph vessels and the regional lymph nodes grow.
 Infectious Bovine Rhinotracheitis
(IBR)
• IBR is an acute and contagious infection usually characterized
by visible signs, including sudden onset of fever, salivation,
rhinitis (red nose), conjunctivitis (red watery eyes), inappetance,
and dyspenea (difficult breathing). It is characterized by
inflammatory lesions in the upper respiratory tract, trachea and
conjunctiva.
 IBR
• The nasal mucosa and muzzle are distinctly inflamed, with abundant nasal
discharge.
• It is caused by bovine herpesvirus-1 (BHV-1). With this virus, diseases such
as infectious pustular vulvovaginitis (EPV) and balanopostitis (inflammation
of the glans penis and prepuce) (IBP), meningoencephalitis, conjunctivitis
and abortion also occur. However, these forms are not usually seen together.
 IBR
• Clinical and virological data show that IBR in cattle has spread around
the world.
• The disease is especially seen in barns where cattle are housed together
in large numbers, and most epidemics occur in animals that are
fattened in a closed area.
• The morbidity rate is high, but in many cases the event is mild or
unnoticed. Its mortality is low.
 IBR
• The disease is milder in dairy cows. The disease starts with the animals
taken from outside the herd and soon becomes epidemic.
• The course of the disease is usually 10 days and sometimes it can be
prolonged.
• After the animal survives active disease, the virus remains latent in the
trigeminal and cyatic ganglia and spreads periodically.
 IBR
• Clinical manifestations are fever, rapid breathing, cough, and serous nasal discharge, these are
always present. If the time is prolonged, the runny nose becomes mucopurulent and
inspiratory dyspnea develops. The nose and its surroundings have a red appearance depending
on these findings and lesions, so the term red nose is also used for the disease.
• Lesions are seromucinous rhinotracheitis and conjunctivitis in typical and uncomplicated
cases. Usually, in severe cases with bacterial complications, there is acute diffuse inflammation,
focal hemorrhages, erosions and ulcerations with mucous or mucopurulent exudate. Diffuse
fibrinous-purulent or fibrinous-necrotic membranes in the nasopharynx, larynx and trachea
mucosa are noted, especially in very severe cases resulting in death.
 IBR
• As with other viral infections of the respiratory system, IBR
lesions, which usually consist of shedding of cilium cells and
necrosis, are followed by repair.
• Fibrinonecrotic rhinotracheitis is frequently encountered in
necropsy in areas with IBR outbreaks. This lesion is caused by the
combined effect of viral-bacterial infections.
 IBR
• Histological changes can be predicted by looking at the macroscopic appearance of
the lesions. In cases that result in death, there is a layer of fibrin and necrotic
masses on the mucosa with extensive epithelial necrosis. Intense vasculitis,
neutrophilic and mononuclear response are observed in the underlying living tissue.
• In the early stages of the disease (first 72 hours), intranuclear eosinophilic inclusion
bodies are found in the upper respiratory tract, bronchiole and sometimes alveolar
epithelium.
 IBR
• IBR has upper respiratory tract inflammation and pneumonia is generally not seen
in the lungs. However, the virus creates a predisposition for the formation of
secondary bacterial infections by disrupting the body defense system.
• When factors such as Pasteurella spp, Mycoplasma spp and Fusobacterium
necrophorum get involved, both pneumonia occurs and the severity of the
inflammation in the upper respiratory tract increases.
• Pneumonia can also occur as a result of direct aspiration of exudate in the airways.
 IBR
• Calves with generalized infection are usually less than one month old, and IBR
infection is present in all age groups in herds with these animals. Fever, serous eye
and nasal discharge are noteworthy in calves. Inspiratory difficulty, anorexia,
depression, and sometimes laryngeal wheezing suggesting laryngeal necrobacillosis
are observed.
• Especially in the lymph nodes draining the upper respiratory tract, acute
lymphadenitis with focal cortical necrosis is seen. Necrotic foci can also be seen in
the kidney, spleen, and liver. Miliary white necrosis foci with a diameter of 1-2 mm in
the liver can be confused with listeriosis.
 Feline Viral Rhinotracheitis
(FVR)
• Feline viral rhinotracheitis is an upper respiratory or pulmonary
infection of cats caused by Felid alphaherpesvirus 1, of the family
Herpesviridae.
• It is an important and common respiratory system disease of cats.
• The disease affects the lung defense mechanism, making animals
susceptible to secondary bacterial pneumonia.
 FVR
• The disease is one of the main components of the cats' respiratory disease complex.
Another component included in this complex is calicivirus infection of cats.
• Viral rhinotracheitis of cats is characterized by fever, sneezing, salivation, mouth
breathing, cough, and nasal and conjunctival discharge ranging from serous to
mucopurulent.
• Most cats recover within 7-14 days, but mortality can be high in young cats or
animals whose immune system is depressed by infection with the feline
immunodeficiency virus or feline leukemia virus.
 FVR
• The causative agent may remain latent in the ganglia.
• The vast majority of cats recovering from the disease become
carriers and shed the virus spontaneously or following stress.
• Sensitive animals (especially kittens with low levels of maternal
antibodies) become infected when exposed to the diseased or
carrier cat.
• Chronic epiphora is seen in carrier cats.
 FVR
• Microscopically, respiratory and conjunctival lesions are associated with
multifocal necrosis characteristic of active herpesvirus infection and
intranuclear viral replication causing necrosis in epithelial cells.
• The lesions are reversible, but secondary infections by microorganisms
such as Mycoplasma felis, Pasteurella multocida, Bordetella
bronchiseptica, Streptococcus spp. cause severe purulent rhinitis and
conjunctivitis.
 FVR
• Lethal cases usually have severe fibrinous rhinotracheitis.
• In addition to these lesions in the respiratory system, the virus also causes
ulcerative keratitis, ophthalmitis, liver necrosis, weakening, abortion and stillbirths.
• Ulcerations of the tongue are rare and only noticeable in severely infected cats.
However, in calicivirus infection of cats, lesions ranging from vesicular to
ulcerative are frequently seen in the tongue and hard palate or nostrils.
• Eye involvement is limited to purulent conjunctivitis, but may progress to
ulcerative keratitis.
 FVR
• Inclusions are typically large and acidophilic, surrounded by a
transparent halo (Cowdry type A).
• Pulmonary involvement is not seen except in fatal cases.
• In fatal viral infection, diffuse multifocal necrotic bronchitis,
bronchiolitis and interstitial pneumonia can be found.
• Secondary bacterial bronchopneumonia can also be seen as a
complication.
 Feline Calicivirus Infection
(FCV)
• Feline calicivirus is a virus of the family Caliciviridae that causes disease
in cats. It is one of the two important viral causes of respiratory
infection in cats, the other being FVR. FCV can be isolated from about
50% of cats with upper respiratory infections.
• Although clinical findings are similar to those seen in FVR, and both
viruses are occasionally found together, calicivirus has an affinity for
the oral and lung epithelium rather than the upper respiratory tract and
conjunctiva.
 FCV
• These two viral diseases constitute 80% of respiratory system
infections of cats.
• Lesions include interstitial pneumonia, prominent ulcers on the
tongue and hard palate, and acute arthritis in addition to rhinitis
and conjunctivitis.