Granulomatous inflammation

1
Granulomatous inflammation
2
Granulomatous inflammation

• A granuloma is a microscopic aggregation of
  macrophages that are transformed into
  epithelium-like cells surrounded by a collar of
  mononuclear leukocytes, principally lymphocytes
  and occasionally plasma cells.

3
Granulomatous Inflammation

• Granuloma Nodular collection of epithelioid
  macrophages surrounded by a rim of lymphocytes
• Epitheloid macrophages squamous cell-like
  appearance

4
Why is it important?

• Granulomas are encountered in certain specific
  pathologic states consequently, recognition of
  the granulomatous pattern is important because of
  the limited number of conditions (some
  life-threatening) that cause it

5
Granulomatous inflammation

• Epithelioid cells fuse to form giant cells
  containing 20 or more nuclei.
• The nuclei arranged either peripherally
  (Langhans-type giant cell) or
• haphazardly (foreign body-type giant cell).
• These giant cells can be found either at the
  periphery or the center of the granuloma.

6
Langhans Giant Cell
Lymphocytic Rim
7
(No Transcript)
8
CAUSES OF GRANULOMATOUS DISEASES
9
Granulomatous Inflammation Causes

• Immune granuloma

• Non-immune granuloma

• Bacteria
• Tuberculosis
• Leprosy
  
• Actinomycosis
  
• Cat-scratch disease
• Parasites
• Schistosomiasis
  
• -Leishmaniasis
• Fungi
• Histoplasmosis
• Blastomycosis
• Metal/Dust
• Berylliosis
• Silicosis

• Foreign body
• Splinter
• Suture
• Graft material

unknown Sarcoidosis
10
(No Transcript)
11
Granulomatous inflammation

• Foreign body Granulomas
• endogenous
• ( keratin, necrotic bone or adipose tissue, uric
  acid crystals)
• Exogenous
• (wood, silica, asbestos, silicone,suture)
• Specific chemicals
• Beryllium

12
Mechanism Of granulomaformation
13
Granulomatous Inflammationmechanism

• What is the initiating event in granuloma
  formation?
• deposition of a indigestible antigenic material
• IFN-? released by the CD4 T cells of the TH1
  subset is crucial in activating macrophages.

14

• Granuloma bacilli are inhaled by droplets
• Bacteria are phagocytosed by alveolar macrophages
• After amassing substances that they cannot
  digest, macrophages lose their motility,
  accumulate at the site of injury and transform
  themselves into nodular collections the
  Granuloma
• A localized inflammatory response recruits more
  mononuclear cells
• The granuloma consists of a kernel of infected
  macrophages surrounded by foamy macrophages and a
  ring of lymphocytes and a fibrous cuff
  (containment phase)
• Containment usually fails when the immune status
  of the patient changes the granuloma caseates,
  ruptures and spills into the airway

15
Granuloma
16
(No Transcript)
17
Tuberculosis
18
Etiology Mycobacterum tuberculosis

• Mycobacteria fungus like..
• slender rods
• acid fast bacilli AFB (i.e., they have a high
  content of complex lipids that readily bind the
  Ziehl-Neelsen carbol fuchsin stain and
  subsequently resist decolorization).
• Mycobacterium bovis ..intestinal TB , milk
  injection
• Other types
• M. leprae (Hansen bacillus) ..Leprosy
• M. kansasii, M. avium, M. intracellulare
  ..Atypical mycobacterial infections
• M. ulcerans .Buruli ulcer

19
AFB - Ziehl-Nielson stain
20
(No Transcript)
21
Pathogenesis of TB
Infection - Immunity
22
If the bacilli enter the body
23
(No Transcript)
24
If the bacilli enter the body

• The bacilli have 4 potential fates
• (1) They may be killed by the immune system,
• (2) they may multiply and cause primary TB,
• (3) they may become dormant and remain
  asymptomatic,
• (4) they may proliferate after a latency period
  (reactivation disease). Reactivation TB may occur
  following either (2) or (3) above.
• (5 ) if immunosuppressed ---- Primary Progressive
  TB Miliary TB

25
(No Transcript)
26
TB

• Primary tuberculosis initial infection
• secondary tuberculosis re-activation or
  re-infection

27
Primary tuberculosis

• Non immunized individual initial infection
  children
• Subpleural zone of lung can be at other sites
• Brief acute inflammation neutrophils.
• 5-6 days invoke granuloma formation.
• 2 to 8 weeks healing Ghon focus ( lymph node
  ? Ghon complex)
• Develop immunity Mantoux positive ( tuberculin
  test , PPD )

28
Primary or Ghons ComplexCharacteristics

• initial infection
• non immunized individual
• 5-6 days granuloma
• 2 to 8 weeks healing
• subpleural zone. Ghon focus
• lymph node ? Ghon complex
• Develop immunity Mantoux positive PPD

29
Secondary Tuberculosis

• Post Primary in immunized individuals.
• Reactivation or Reinfection
• Cavitary Granulomatous response.
• Apical lobes or upper part of lower lobes O2
• Caseation, cavity - soft granuloma
• Pulmonary or extra-pulmonary
• Local or systemic spread / Miliary
• Vein via left ventricle to whole body
• Artery miliary spread within the lung

30
Secondary Tuberculosis

• Cough, sputum, Low grade fever, night sweats,
  fatigue and weight loss.
• Hemoptysis or pleuritic pain severe disease

31
Miliary TB

• Millet like grain.
• Low immunity
• blood or bronchial spread
• Pulmonary or Systemic types.

32
TB OF DIFFERENT ORGANS
33
Adrenal TB - Addison Disease
34
Testes TB Orchitis.
35
TB Peritonitis liver Miliary TB
36
TB Brain Caudate n.
37
(No Transcript)
38
TB Intestineany part can be affectedileum
39
Prostate TB
40
Spinal TB - Potts Disease
41
Diagnosis of TB

• Clinical features
• Depend on organ involved.
• Pulmonary tuberculosis (TB)
• productive cough, fever, and weight loss, night
  sweats.

42
Investigations

• Patients suspected of having tuberculosis (TB)
• Tuberculin skin testing (Mantoux test, PPD)
• Intradermal injection of purified protein
  derivative ( PPD).
• The response is measured as the amount of
  induration at 48-72 hours.
• The size of induration, rather than erythema, is
  diagnostic.
• BCG gives result
• Sputum, bronchial wash or biopsy
• Acid fast smear ( ZN stain )
• cultures require weeks for growth and
  identification
• Newer technologies, including ribosomal RNA
  probes or DNA polymerase chain reaction, allow
  identification within 24 hours.
• Chest radiographs
• patchy or nodular infiltrate.
• may be found in any part of the lung, but
  upper-lobe involvement is most common

43
PPD result after 72 hours
44
(No Transcript)
45
What will be your action after diagnosis?

• Patients with TB should remain in isolation until
  sputum becomes negative

46

• 1 TB usually involves the middle or lower lung
  zones and is associated with hilar adenopathy
  (Gohn complex).
• 2 TB represents reactivation and typically
  involves the upper lungs and cavitation.
• regimen RIPERifampin, Isoniazid (INH),
  Pyrazinamide, and Ethambutol daily for eight
  weeks, followed by INH and rifampin for an
  additional 16 weeks. Give vitamin B6 to prevent
  INH-associated neuropathy.

47
Leprosy
48
Leprosy

• Leprosy is a chronic infection caused by the
  acid-fast, rod-shaped bacillus Mycobacterium
  leprae.
• skin
• peripheral nerves

49
Leprosy Symptoms

• skin
• Painless skin patch
• peripheral nerves
• Loss of sensation
• Wasting and muscle weakness
• Foot drop or clawed hands
• Ulcerations on hands or feet

50
Aetiology

• Mycobacterium leprae
• Acid fast gram-positive bacillus
• cannot be cultured
• The mode of transmission is unknown, probably
  inhalation of bacilli
• incubation period is several years.
• The classical method for demonstrating leprosy
  bacilli in lesions is a modified Ziehl-Neelsen
  stain. The Fite methods are the most commonly
  used

51
Classification

• Depends on the strength of the delayed (type IV)
  hypersensitivity response in the infected
  individual.
• Lepromatous leprosy
• poor Cell-mediated immunity
• bacilli are plentiful
• large numbers of macrophages
• Sensation is not impaired
• Tuberculoid leprosy
• strong cell-mediated immunity
• Few or no acid-fast bacilli.
• granulomatous reaction in the nerves and dermis
• anaesthesia
• Indeterminate leprosy

52
The lepromin skin test

• Intradermal injection of a preparation of M.
  leprae
• A positive reaction consists of the formation of
  a nodule measuring 5 mm or more in diameter after
  2 to 4 weeks. On histologic examination, the
  nodule shows an epithelioid cell granuloma.
• Tuberculoid ..
• lepromatous ..

53
DIAGNOSISSKIN BIOPSY

• Tuberculoid leprosy
• granulomatous dermatitis
• Few acid-fast bacilli in nerves
• intraneural granuloma
• Lepromatous leprosy
• a mass of macrophages in the dermis (no granuloma
  formation), leaving a clear grenz zone under the
  epidermis

54
Schistosomiasis
55
Schistosomiasis

• Also known as bilharziasis
• Parasite
• The main forms of human schistosomiasis
• Schistosoma hematobium,
• Schistosoma mansoni,
• Schistosoma japonicum,
• Schistosoma intercalatum,
• Schistosoma mekongi.

56
Life cycle
57
Life cyclepathophysiology

• Cercaria
• Infective stage
• Cercarial dermatitis..itching
• Adult worm
• In the venous blood
• lays eggs 4-6 weeks after cercarial penetration.
• rarely pathogenic.
• Eggs
• Pathogenic
• Diagnostic

58
Acute schistosomiasis

• most clinical manifestations are benign
• Cercarial dermatitis Individuals who have been
  exposed to fresh or salt water may develop a
  pruritic rash due to cercarial dermatitis (also
  called swimmer's itch).
• some are severe and may require hospitalization.

59
Chronic schistosomiasis

• Most patients are asymptomatic or mildly
  symptomatic and do not require medical attention.
• Only a small proportion of the endemic population
  harbors a heavy worm burden that later leads to
  clinical complications.

60
clinical complications.

• Liver
• S mansoni S japonicum,
• periportal fibrosis, ----portal hypertension and
  gastrointestinal hemorrhage.
• Liver failure is uncommon
• Urinary tract
• S hematobium,
• obstructive uropathy, or bladder carcinoma (
  sequamous cell carcinoma)
• Other organs lung , brain

61
Diagnosis

• Stool
• urine analysis
• Rectal or bladder biopsy
• Serology

62
Leishmaniasis
63
Leishmaniasis

• Protozoal disease.
• transmitted to human via the bite of the female
  sandfly
• Animal reservoir is required to persist.

64
Leishmaniasis Life cycle
65
Leishmaniasis

• Cutaneous
• L. tropica .middle east
• L. major
• exposed parts of the body, such as face, scalp,
  and arms
• Ulceration is common
• Mucocutaneous
• L. b. braziliensis
• lips , oral cavity, pharynx, nose
• Disfiguring tissue distruction
• Visceral (kala-azar
• L. donovani
• L. tropica
• fever, lymphadenopathy, hepatosplenomegaly,
  ascites, pancytopenia, may die if untreated
• Indian name kala-azar black fever ..diffuse
  darkening of the skin,

66
DIAGNOSIS

• Tissue sample
• Direct visualization of amastigotes
• Culture
• PCR

67
DIAGNOSIS

• Tissue sample
• Direct visualization of amastigotes
• Culture
• PCR

Lieshman-donovan body
68
Sarcoidosis

• systemic disease of unknown cause
• noncaseating granulomas in many tissues and
  organs.
• many clinical patterns, but
• bilateral hilar lymphadenopathy or lung
  involvement is visible on chest radiographs in
  90 of cases.
• Eye and skin lesions are next in frequency.

69
Sarcoidosis Etiology and Pathogenesis

• The etiology of sarcoidosis remains unknown
• cell-mediated response to an unidentified
  antigen.
• Intra-alveolar and interstitial accumulation of
  CD4 T cells
• Increased levels of TH1 cytokines such as IL-2
  ,IFN-?
• Polyclonal hypergammaglobulinemia. manifestation
  of helper T-cell dysregulation

70
Microscopic findings

• Noncaseating granulomas
• Schaumann bodies laminated concretions composed
  of calcium and proteins
• asteroid bodies enclosed within giant cells
• Although characteristic, these microscopic
  features are not pathognomonic of sarcoidosis
  because asteroid and Schaumann bodies may be
  encountered in other granulomatous diseases
  (e.g., tuberculosis).

71
Any Organs involved

• Lungs common sites of involvement
• Lymph nodes are involved in almost all cases,
  specifically the hilar and mediastinal nodes
• Spleen
• bone marrow
• Skin lesions
• eye,
• salivary glands

72
Bilateral hilar adenopathy
73
Clinical Course

• In the great majority of cases, patients seek
  medical attention because of the
• respiratory abnormalities (shortness of breath,
  cough, chest pain, hemoptysis) or
• constitutional signs and symptoms (fever,
  fatigue, weight loss, anorexia, night sweats).

74
Prognosis

• 65 to 70 recover with minimal or no residual
  manifestations.
• 20 permanent loss of some lung function or
  some permanent visual impairment.
• 10 to 15, some die of cardiac or central
  nervous system damage,

75
(No Transcript)