1 03.09.2014 pathology

Acute , acute viral respiratory infection Ivan Sakharau, assist. lect. Acute

 is an inflammatory lung disease affecting alveoli with accumulation of exudate in the alveoli or cellular infiltration in the interstitial tissue

3 03.09.2014 “Pneumonia”

 from Ancient Greek πνευμονία (pneumonia, “lung disease”), from πνεύμων (pneumōn, “lung”)

4 03.09.2014 Classification

 1. Etiology  biological agents: , viruses, fungi, protozoa, mixed infections  chemical factors: a vapours of chemicals, uremia  physical factors: industrial dust, ionizing radiation

Ways of contamination:  airborne  aspiration from naso- and oropharynx  hematogenous infection of extrapulmonary lesions  from neighbour infected sites

5 03.09.2014 Classification  2. Pathogenesis  Primary: there are laws on its own etiopathogenetic  Secondary: a manifestation of another, as a rule, system or extrapulmonary disease

Risk factors:  airway infection (usually viral)  obstructive changes in bronchi  immunodeficiencies, hypothermia, stress  alcohol and tobacco  inhalation of toxic substances and dusts  wounds and injuries, post-operative period  early childhood and old age

6 03.09.2014 Classification

 3. Prevalence  unilateral, bilateral  acinar, miliary, lobular, segmental, polysegmentary, lobar, total

7 03.09.2014 Classification

 4. Clinical and morphological features  (focal p.)  interstitial pneumonia

“Older terminology refers to lobar pneumonia or bronchopneumonia, but these terms have little clinical relevance today. In general, lobar pneumonia refers to consolidation of an entire lobe while bronchopneumonia is scattered solid foci in the same or several lobes” (Rubin's Pathology : Clinicopathologic Foundations of Medicine, 5th Edition)

8 03.09.2014 Differential clinical and morphological characteristics Feature Lobar pneumonia Bronchopneumonia Etiology Pneumococci (Streptococci Bacteria, viruses, fungi, pneumoniae I, II, III, IV types), mycoplasma, chlamidia, chemical and physical factors Pathogenesis • Preceding sensibilisation to After acute and microbial agent • Triggering factor (hypothermia, trauma) Clinical signs Acute onset, rapid Manifestations increase development gradually

9 03.09.2014 Differential clinical and morphological characteristics Feature Lobar pneumonia Bronchopneumonia Exudate Fibrinous or fibrino-purulent Serous, purulent, haemorrhagic, fibrinous, putrid, mixed Affected lung 1 lobe (right lower is most Acini, lobuli, segment(s) volume common), 2 lobes, 3 lobes Prevalent • Young adults, adults • All ages patients age • Always primary • Usually secondary (primary in infants and elderly patients) Staging 4 stages No

10 03.09.2014 Lobar pneumonia – clinical signs

11 03.09.2014 Lobar pneumonia – staging

 1. Initial (1st day)  a lobe rapidly becomes red and swollen  protein-rich edema fluid containing numerous bacteria fills the alveoli (“microbial edema”)  some amount of alveolar and leukocytes is seen  fibrin is seen at the end of the day  as a rule also develops in the pleura (pleuritis)  bronchi remain intact during all stages (inflammation develops only in alveoli)

12 03.09.2014 Lobar pneumonia – initial stage

13 03.09.2014 Lobar pneumonia – initial stage

14 03.09.2014 Lobar pneumonia – staging

 2. Red hepatization (2nd-3rd days)  marked capillary congestion leads to massive outpouring of polymorphonuclear leukocytes and intra-alveolar hemorrhage  affected lobe is of firm consistency and reminiscent of the

15 03.09.2014 Lobar pneumonia – red hepatization

16 03.09.2014 Lobar pneumonia – red hepatization

17 03.09.2014 Lobar pneumonia – staging

 3. Grey hepatization (4th-6th days)  lysis of polymorphonuclear leukocytes and erythrocytes  macrophages phagocytose the fragmented blood cells  lobe is still firm and grey due to fibrin in alveoli

18 03.09.2014 Lobar pneumonia – grey hepatization

19 03.09.2014 Lobar pneumonia – grey hepatization

20 03.09.2014 Lobar pneumonia – grey hepatization

21 03.09.2014 Lobar pneumonia – staging

 4. Resolution (up to 2 weeks)  fibrinolysis  alveolar exudate is then removed while coughing  lung gradually returns to normal

22 03.09.2014 Lobar pneumonia – complications

 Pleuritis, often painful, is common, because the pneumonia readily extends to the pleura  pleura is usually involved; sometimes “lobar pneumonia” is called “pleuropneumonia”  occurs frequently, but usually resolves  Pyothorax results from infection of a pleural effusion, and may heal with extensive fibrosis

23 03.09.2014 Lobar pneumonia – pleuritis

24 03.09.2014 Lobar pneumonia – complications

. The intra-alveolar exudate organizes to form intra-alveolar plugs of granulation tissue. Gradually, increasing alveolar fibrosis leads to a shrunken and firm lobe, a rare complication known as carnification

25 03.09.2014 Lobar pneumonia – pulmonary fibrosis

26 03.09.2014 Lobar pneumonia – complications

due to destruction of lung tissue by enzymes of leucocytes and macrophages. A cavity is formed filled with pus and surrounded by fibrous tissue.

27 03.09.2014 Lobar pneumonia – lung abscess

28 03.09.2014 Lobar pneumonia – complications

 Gangrene due to necrosis of lung tissue.  dark coloration is due to liberation of hemoglobin from hemolyzed red blood cells, which is acted upon by hydrogen

sulfide (H2S), resulting in formation of black iron sulfide that remains in the tissues

29 03.09.2014 Lobar pneumonia – gangrene

30 03.09.2014 Lobar pneumonia – complications

 Spreading of the infection:  Hematogenous: bacteremia occurs in the early stages of pneumococcal pneumonia in more than 25% of patients, and may lead to endocarditis, meningitis, brain abscess, arthritis or sepsis.  Lymphogenous: pericarditis and .

31 03.09.2014 Lobar pneumonia – spreading of the infection

Pericarditis Meningitis

32 03.09.2014 Lobar pneumonia – spreading of the infection

Sepsis: septicopyemia

33 03.09.2014 Bronchopneumonia  Various etiology: bacteria, viruses, fungi, mycoplasma, chlamidia, chemical and physical factors  Affects acini, lobuli, segment(s) (and up to lobes)  Develops after and bronchiolitis  low bronchial drainage leads to penetration of bacteria to respiratory parts of the lung (alveoli)  morphological features differ due to various etiology

34 03.09.2014 Bronchopneumonia

35 03.09.2014 Bronchopneumonia

36 03.09.2014 Bronchopneumonia

37 03.09.2014 Bronchopneumonia

 Can develop as autoinfection:  after aspiration of upper airway content (aspiration p.)  due to blood congestion (hypostatic p.) - confined to the bed or weakened patients  after surgical intervention (postoperative p.) due to secondary immunodeficiency

38 03.09.2014 Bronchopneumonia – streptococcus

 caused by hemolytic streptococci group A and B  very often mixed infection (+ viral infection)  often seen in patients with diabetes  affects the lower lobes  sero-purulent exudate with interstitial component  sometimes abscesses and bronchiectases are formed

39 03.09.2014 Bronchopneumonia – streptococcus

40 03.09.2014 Bronchopneumonia – pneumococcus

 caused by pneumococci (Streptococci pneumoniae I, II, III, IV types)  exudate contain fibrin and PMN leucocytes

41 03.09.2014 Bronchopneumonia – pneumococcus

42 03.09.2014 Bronchopneumonia – staphylococcus

is a common pulmonary superinfection after and other viral infections.  nosocomial staphylococcal pneumonia typically occurs in chronically ill people who are prone to aspiration, and in intubated patients  characterized by abscess development  abscess can rupture into the and cause a tension and pleural effusions

43 03.09.2014 Bronchopneumonia – Pseudomonas aeruginosa

 most often seen in patients who are immunocompromised  often an infectious vasculitis, in which large numbers of organisms can be seen in blood vessel walls  results in pulmonary infarction.

44 03.09.2014 Bronchopneumonia – fungi

 caused by various fungi (Candida most often)  marked alteration seen as necrosis  proliferative inflammation and granuloma formation  fungi elements in exudate and in the center of granulomas

45 03.09.2014 Bronchopneumonia – fungi

46 03.09.2014 Bronchopneumonia – viruses

 most often in infants and children  serous, fibrinous, hemorrhagic exudate  hyaline membranes in alveoli  alveolar epithelium contains viral inclusion and often is desquamated

47 03.09.2014 Pneumonias in children  Etiology: viral, mycoplasma, bacterial, rickettsial, parasitic, fungal, mixed  The most common microbial agents: Klebsiella, Pseudomonas aeruginosa, Proteus, E. coli, Staphylococcus  Mixed viral-bacterial predominate  Predisposing factors:  congenital defects of respiratory tract and  congenital and acquired the immunodeficiencies  immaturity of the lung tissue in preterm newborns  aspiration of amniotic fluid in utero or during delivery  mechanical ventilation  surfactant deficiency

48 03.09.2014 Pneumonias in elderly patients  Etiology: bacterial (Str.pneumoniae, , , etc.), viral (flu), mycoplasma  Autoinfection is of great value  Predisposing factors:  decreased immunity,  impaired mucociliary clearance  cardiopulmonary failure  weakening of the cough reflex  impaired swallowing process  Atypical clinical presentation  Suppurative and destructive complications

49 03.09.2014 Interstitial pneumonia

 = “, alveolitis”  Primary inflammation in the interalveolar and peribronchial stroma  Etiology: viruses, mycoplasma, fungi, Pneumocystis  Develop as hypersensitivity reaction I (immediate) and IV (delayed) types  interstitial fibrosis in outcome

50 03.09.2014 Interstitial pneumonia

51 03.09.2014 Acute viral respiratory infection (AVRI)

 group of acute inflammatory diseases of the , similar in clinical presentation and morphology caused by pneumotropic viruses

“The (also known as nasopharyngitis, rhinopharyngitis, acute coryza, or a cold) is a viral infectious disease of the upper respiratory tract which primarily affects the nose. Symptoms include coughing, sore throat, runny nose, sneezing, and which usually resolve in seven to ten days, with some symptoms lasting up to three weeks. Well over 200 viruses are implicated in the cause of the common cold; the rhinoviruses are the most common.” Wikipedia, “Common cold”

52 03.09.2014 AVRI - pathogenesis

 1. Cytopathic effect:  virus adsorption and penetration

 Morphology:  cytoplasmic and/or intranuclear inclusion  giant cell formation  cell degeneration, necrobiosis and necrosis  desquamation  regeneration and proliferation  the formation of multilayered beds  inflammatory infiltration (lymphocytes, plasma cells, macrophages, single )

53 03.09.2014 AVRI - pathogenesis

 2. Vasopathic effect:  endothelium of capillaries is affected

 Morphology:  vascular paresis and dilatation  hyperemia  an increase in vascular permeability  stasis  thrombosis of capillaries  edema, hemorrhage

54 03.09.2014 AVRI - pathogenesis

 3. Immunosuppressive effect  affect of immune organs, secondary ID

 Morphology  reactive hyperplasia of lymphatic tissue  then – accidental transformation and atrophy of the thymus, lymphocyte depletion in peripheral immune organs

 4. Spreading and generalization of infection  through airways  haematogenous

55 03.09.2014 Influenza (flu)

 RNA viruses of the family Orthomyxoviridae  According to virion internal proteins (M1 and NP) viruses divided into Influenza virus A, B, C  Surface proteins – hemagglutinin (HA) and neuraminidase (NA) – determ serotypes  Viruses affecting people contain  three subtypes of HA (H1, H2, H3)  two subtypes of NA (N1, N2)  serovariants of A Influenza virus A (less often B) can change Ag-structure in vivo

56 03.09.2014 Known flu pandemics Name of Date Deaths Case fatality Subtype Pandemic pandemic rate involved Severity Index 1889–1890 1889–1890 1 million 0.15% possibly H3N8 N/A flu pandemic or H2N2 (Asiatic or Russian Flu) 1918 flu 1918–1920 20 to 100 2% H1N1 5 pandemic million (Spanish flu) Asian Flu 1957–1958 1 to 1.5 0.13% H2N2 2 million Hong Kong Flu 1968–1969 0.75 to 1 <0.1% H3N2 2 million Russian flu 1977–1978 no accurate N/A H1N1 N/A count 2009 flu 2009–2010 18,000 0.03% H1N1 N/A pandemic (Swine)

57 03.09.2014 Influenza (flu)

 Airborne and transplacental transmission  Incubation period 2-4 days  Local changes are associated with the cytopathic and vasopathic effects of virus  Catarrhal tracheobronchitis  General changes associated with viremia and intoxication  degenerative, inflammatory changes of inner organs, circulatory disorders.

58 03.09.2014 Influenza (flu) – clinical forms

 1. Mild  catarrhal laryngotracheobronchitis (upper airways)  degeneration and desquamation of the respiratory epithelium  hypersecretion of mucus  edema  complete restoration of the epithelium (on 5th day)

59 03.09.2014 Influenza (flu) – clinical forms

 2. Moderate  small bronchi, and lung parenchyma  serous-hemorrhagic inflammation  interstitial infiltration in lung  hyaline membranes and giant cells in alveoli  squamous metaplasia of the bronchial epithelium

60 03.09.2014 Influenza (flu) – clinical forms

 3. Severe – two types  with marked intoxication (due to the cytopathic and vasopathic effects of virus).  with pulmonary complications (due to the addition of a secondary infection).

61 03.09.2014 Influenza (flu) – Severe with marked intoxication

and bronchi: a pronounced serous-hemorrhagic inflammation and necrosis  Lungs: massive hemorrhage, numerous small foci of serous-hemorrhagic pneumonia, acute emphysema and atelectases  Inner organs: numerous hemorrhages  Serous (serous-hemorrhagic) meningitis, meningoencephalitis, cerebral edema

62 03.09.2014 Influenza (flu) – Severe with pulmonary complications

 Upper respiratory tract: sero-purulent or fibrino- hemorrhagic inflammation  Bronchi: destructive panbronchitis (entire bronchial wall envolved)  Lungs: bronchopneumonia with a tendency to abscess formation, necrosis, hemorrhage, development of and emphysema, marked interstitial component

63 03.09.2014 Influenza A1N1

64 03.09.2014 Influenza A1N1

65 03.09.2014 Influenza A1N1

66 03.09.2014 Influenza A1N1

67 03.09.2014 Influenza A1N1

68 03.09.2014 Parainfluenza

 group of four distinct serotypes of RNA viruses of the family Paramyxoviridae  common in children under the age of 3 years and is characterized by subglottic swelling  the most common cause of , which is characterized by stridor on inspiration and a “barking” cough

69 03.09.2014 Parainfluenza

 infects and kills ciliated epithelial cells of upper respiratory tract  in very young children this process frequently extends into the lower respiratory tract, causing bronchiolitis and pneumonitis  in young children, where the trachea is narrow and the is small, the local edema of laryngotracheitis compresses the upper airway enough to obstruct breathing and cause croup

70 03.09.2014 Adenovirus infection

 Adenoviruses belong to group of DNA viruses of the family Adenoviridae  can cause respiratory affection, gastroenteritis, conjunctivitis, cystitis

71 03.09.2014 Adenovirus infection specific presentation of adenovirus infection is “pharyngoconjunctival fever”:

 high fever that lasts 4–5 days   conjunctivitis  enlargement of the lymph nodes of the  headache, malaise, and weakness

72 03.09.2014 Adenovirus infection

73 03.09.2014 Adenovirus infection

74 03.09.2014 RSV infection

 respiratory syncytial virus (RSV) is RNA viruses of the family Paramyxoviridae  most children have been infected with the virus by age 2  in adults and older, healthy children, the symptoms of RSV are mild and typically mimic the common cold  infection can be severe in some cases, especially in premature babies, transplant patients and other immunocompromised persons  virus causes the cell membranes on nearby cells to merge, forming syncytia

75 03.09.2014 RSV infection

76 03.09.2014 Mycoplasma infection  Mycoplasmas refers to a genus of bacteria that lack a cell wall  the smallest self-replicating organisms  at first, they were considered viruses; then intermediate between viruses and bacteria  M. pneumoniae and some other mycoplasmas can cause human infection  tracheobronchitis is most common in children  primary can develop  usually it occurs in younger age groups and may be associated with neurological and systemic (e.g. rashes) symptoms

77 03.09.2014 Mycoplasma infection

 alveoli are filled with edematous fluid, macrophages, fewer lymphocytes and detached alveolocytes  alveolocytes have foamy cytoplasm containing PAS positive granules (mycoplasmas)

78 03.09.2014 Mycoplasma infection

79 03.09.2014 Mycoplasma infection

80 03.09.2014 Thank you!

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