L-20 Pathology of Infectious disease II

Viral Respiratory Infections

• Major pathologic features of viral respiratory infections, digestive system viral diarrheas, Rotaviruses, and Norwalk agent gastroenteritis will be covered.
• The impact of viruses on the lower respiratory tract will be discussed with an overview of the respiratory system, including normal histology of the tracheobronchial tree and lungs.

Viral Effects on the Lower Airway

• Influenza can cause tracheobronchitis where the epithelial surface of the airway appears fiery red due to acute inflammation and mucosal congestion.
• Parainfluenza leads to viral pneumonia.
• Adenovirus causes extensive bronchiolitis which heals via fibrosis and can obliterate or occlude bronchioles (constrictive bronchiolitis).
• Respiratory Syncytial Virus (RSV) often occurs in nurseries and is most common in newborns/infants under one year old
• RSV is usually self-limited but can sometimes be fatal, causing peribronchiolar inflammation with epithelial disorganization affecting small bronchiolar epithelium and type I and II pneumocytes.
• Viral pneumonitides cause diffuse alveolar damage or interstitial pneumonia.

Coronaviruses

• Coronaviruses are the largest of all RNA viruses and classified into alphacoronavirus, betacoronavirus, gammacoronavirus, and deltacoronavirus.
• SARS-CoV is a B betacoronavirus responsible for the severe acute respiratory syndrome outbreaks in 2002-2003.
• MERS-CoV is a C betacoronavirus, and was first reported in Saudi Arabia in 2012, establishing infection in monocyte-derived macrophages triggering release of proinflammatory cytokines causing severe inflammation and tissue damage that can manifest as severe pneumonia and respiratory failure

SARS-CoV-2

• SARS-CoV-2 causes diffuse alveolar damage (DAD), a reaction pattern of alveolar epithelial and endothelial cells to acute insults.
• Severe DAD’s clinical expression is acute respiratory distress syndrome (ARDS).
• In ARDS, genes encoding angiotensin-converting enzyme (ACE), Interleukin 10 (IL-10), tumor necrosis factor (TNF), and vascular endothelial growth factor (VEGF) are biomarkers.
• ACE has been linked to ARDS susceptibility, ACE2 protein is a receptor for severe acute respiratory syndrome coronavirus.
• ARDS can cause diffuse alveolar damage where the lumen of the alveolar space is replaced by a thick, homogenous eosinophilic layer of fibrin.
• Acute ARDS can cause alveolar septa thickened by edema and sparse inflammatory infiltrate and the alveoli are lined by eosinophilic hyaline membranes.
• The alveolar walls are thickened by fibroblasts and loose connective tissue in the acute, organizing phase of ARDS

Orthomyxoviruses - Influenza (Flu)

• Influenza targets epithelial cells of the respiratory tract- causing an acute, self-limited, upper airway infection
• Influenza A causes pandemics, infecting humans and animals.
• Influenza B causes seasonal epidemics, primarily in humans.
• Influenza C causes milder illness and is less common.
• Influenza infection is the necrosis and desquamation of the ciliated epithelium, with lung involvement leading to pneumonitis.
• Severe influenza infections (H5N1, H7N9) trigger high levels of pro-inflammatory cytokines, leading to severe lung damage and high mortality.

Rotavirus

• Rotavirus causes gastroenteritis and it's responsible for about 50% of childhood diarrhea cases and 1/3 of adult diarrhea hospitalizations
• Rotavirus common in fall, winter, and spring.

Rotavirus Disease

• Pathology & Clinical Manifestations include, Profuse diarrhea lasting >24 hours, vomiting, black or tarry stool, and/or high fever leading to dehydration and potential death.
• ~800,000 global deaths occur a year, primarily in elderly & undernourished patients

Norwalk Agents (Norovirus)

• Norwalk Agents characteristics include a single-stranded RNA (SS-RNA) virus that most commonly causes acute gastrointestinal illness in children, and replicates in macrophages, dendritic cells, and B cells.
• Norwalk agents invade enterocytes lining the gut lumen with an incubation period of about 1 day.
• Norwalk Agents cause acute gastroenteritis, causing nausea, forceful vomiting, watery diarrhea, and abdominal pain.
• Norwalk infection is self-limiting

Herpesvirus Infections

• Herpes Simplex type-I and II, Varicella-Zoster, and CMV are the chronic Herpetic infections with Herpes simplex type-I and II, Varicella-Zoster (lecture 19), and Cytomegalovirus.
• Latency is defined as the persistence of infectious viral genomes in cells that do not produce a virus
• Dissemination stems from reactivation of latent virus.
• With Herpes, the latent virus creates blisters showing glassy intranuclear viral inclusion bodies.
• H. Simplex Type I can cause Keratoconjunctivitis (corneal ulcer). Meningoencephalitis & hemorrhagic lesions can also arise in the temporal lobe.

CMV (Cytomegalovirus)

• CMV (Cytomegalovirus) infects and remains latent in white blood cells and reactivates when cellular immunity is depressed, causing enlarged cells, large nuclei, and basophilic intranuclear inclusion bodies (owl's eye in most organs).
• CMV usually remains asymptomatic, though sometimes causing mononucleosis or viral pneumonia after reactivation.

Cytomegalovirus Pneumonitis

• Cytomegalovirus Nuclear inclusions in pneumonitis are usually basophilic, round to oval, with a peripheral halo and accentuation of the nuclear membrane.

Epstein Barr Virus (EBV)

• Epstein Barr virus (EBV) infections lead to Infectious Mononucleosis in American and European patients, Burkitt Lymphoma in African children, B cell lymphoma in immune-suppressed patients, and Nasopharyngeal carcinoma in China, Malaysia, and Singapore.
• After initial infection, EBV infects B lymphocytes and remains detectable in oropharyngeal secretions
• EBV remains in the B lymphocytes, for life and undergoes intermittent asymptomatic shedding from the oropharynx
• EBV is associated with Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma, and certain gastric cancers

Infectious Mononucleosis (IM)

• Infectious Mononucleosis (IM) results from the Epstein-Barr virus (human herpesvirus type 4) after EBV infects B lymphocytes (mostly CD8+ T).
• Clinical features include fever, pharyngitis, lymphadenopathy, splenomegaly, periorbital edema & palatal petechiae

Nasopharyngeal Carcinoma (NPC)

• Nasopharyngeal carcinoma (NPC) is a primary mucosal malignancy arising in the nasopharynx in close proximation to lymphoid tissue
• NPC linked to the Epstein-Barr virus and has a distinctive geographic relationship to Southeast Asia, occurring most notably in Southern China, Hong Kong, Singapore, Malaysia, and Taiwan.
• NPC is Keratinizing (previously type I), originating from nasopharyngeal mucosa showing evidence of squamous differentiation, but with no relationship to EBV.
• NPC may also be Nonkeratinizing, with a strong association with EBV, with EBV DNA found in tumor cells and in premalignant (dysplastic, in situ) lesions.
• Clinically, a peak in incidence occurs typically 40 to 60-years with bloody nasal discharge or epistaxis.
• 50-70% present with mass from metastatic nodes: Unilateral lymphadenopathy and/or serous otitis from eustachian tube obstruction.

Nasal-Type Angiocentric Natural Killer/T-Cell Lymphoma

• Nasal-Type Angiocentric Natural Killer/T-Cell Lymphoma shows EBV identified in more than 95% of cases
• NK-/T-cell lymphoma, nasal type is strongly associated with EBV irrespective of ethnic background.
• Nasal type is more likely after organ transplantation or with Hyper-IgE syndrome (Job syndrome) and includes extranodal NK-/T-cell lymphoma which is a rare primary immunodeficiency that increases risk for malignancies.
• Clinically, it's a destructive process in the midfacial region causing facial deformities if left untreated.

Questions about the impact of specific viruses, such as adenovirus and RSV, on the lower respiratory system. Includes pathological manifestations, affected areas, and common characteristics of viral infections in different age groups.