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Methods to study Histology

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Methods to study Histology Powered By Docstoc
					Dr.T.Krishna MD, www.mletips.co m
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Dr.T.Krishna MD, www.mletips.co m
     Sjögren Syndrome
     Sicca syndrome,
      ◦ Dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia)
     Etiology and Pathogenesis
      ◦ lymphocytic infiltration and fibrosis of the lacrimal and salivary glands
     Immune factors
      ◦ Predominantly CD4+ & some B cells play role
      ◦ ANAs in 50% to 80%
      ◦ Ribonucleoprotein antigens =SS-A (Ro) and SS-B (La)- (Most important
        & seen in 90% of patients )
     Morphology
      ◦ Salivary glands = earliest change - peri ductal and perivascular
        lymphocytic infiltration; later lymphoid follicles with germinal centers;
        salivary duct obstruction acinar atrophy & fibrosis
      ◦ Lacrimal glands = lack of tears -drying ,inflamed, eroded, and ulcerated
        corneal epithelium
      ◦ Oral cavity = mucosal atrophy, fissuring and ulceration
      ◦ Kidney= tubulointerstitial nephritis (glomerular lesions-extremely rare)
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    Dr.T.Krishna MD, www.mletips.co m
Clinical Manifestations
      ◦ older women (50 and 60’s)
     Eyes
      ◦ blurring of vision, burning, and itching, and thick secretions
     Mouth
      ◦ Xerostomia difficulty in swallowing solid foods, a decrease in the
        ability to taste, cracks and fissures in the mouth, and dryness of the buccal
        mucosa; Parotid gland enlargement ( in 50%)
     Nose
      ◦ Dryness of the nasal mucosa, Epistaxis, recurrent bronchitis, and
        pneumonitis
     Extra glandular disease
      ◦ Synovitis, diffuse pulmonary fibrosis, and peripheral neuropathy
     Mikulicz disease
      ◦ combination of lacrimal and salivary gland inflammatory involvement
     Mikulicz syndrome
      ◦ Bilateral enlargement of Salivary & lacrimal glands of whatever cause-
        Sarcoidosis, leukemia, lymphoma, and other tumor)

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    Dr.T.Krishna MD, www.mletips.co m
   Nose
    ◦ dryness of the nasal mucosa, epistaxis, recurrent bronchitis, and
      pneumonitis
   extraglandular disease
    ◦ synovitis, diffuse pulmonary fibrosis, and peripheral neuropathy
   Mikulicz disease
    ◦ combination of lacrimal and salivary gland inflammatory involvement
   Mikulicz syndrome
    ◦ lacrimal and salivary gland enlargement of whatever cause
    ◦ Sarcoidosis, leukemia, lymphoma, and other tumor
   Diagnosis
    ◦ biopsy of the lip (to examine minor salivary glands) is essential for the
      diagnosis of Sjögren syndrome.
   Prognosis
       40-fold increased risk of non-Hodgkin lymphomas
    (NHL)
    ◦ B-cell type
    ◦ in the salivary glands and lymph nodes

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Dr.T.Krishna MD, www.mletips.co m
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Dr.T.Krishna MD, www.mletips.co m
     chronic disease of unknown etiology
     abnormal accumulation of fibrous tissue in the skin and multiple organs
     MC affected organ -skin
      ◦ others -gastrointestinal tract, kidneys, heart, muscles, and lungs
     Categories :
     1) Diffuse scleroderma
      ◦ widespread skin involvement at onset
      ◦ rapid progression
      ◦ early visceral involvement
      ◦ Anti DNA topoisomerase I Ab (anti-Scl 70)
     (2) Limited scleroderma or CREST syndrome
      ◦ Calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly,
         and telangiectasia,
      ◦ Skin involvement is confined to fingers, forearms, and face
      ◦ Visceral involvement is late
      ◦ Course is relatively benign
      ◦ Anti centromere Ab


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    Dr.T.Krishna MD, www.mletips.co m
     Etiology and Pathogenesis
      ◦ unknown etiology
      ◦ trigger for excessive fibrosis
      ◦ abnormal immune responses and vascular damage  resulting in local
        accumulation of growth factors that act on fibroblasts (hypersensitive to
        cytokines)  stimulate collagen production
      ◦ CD4+ T cells (TH2 ) seen in skin & responding to cytokines
     Genetic component
      ◦ Genes encode or regulate fibrillin-1 &HLA class II genes
     Morphology
      ◦ Early stages
         Micro vascular disease
           Intimal proliferation of 100% of digital arteries
           Capillary dilation, leaking, destruction, nail fold capillary loops are
             distorted
         Signs of endothelial injury
           Cause= Granzyme A of CD8+ T cells
           Proof = increased levels of von Willebrand factor
         Platelet activation Circulating platelet aggregates

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    Dr.T.Krishna MD, www.mletips.co m
     Progression
      ◦ Epidermis- thinning, loss of rete pegs, atrophy of appendages
      ◦ Dermis -↑ fibrosis & ↑ of compact collagen
      ◦ Subcutaneous calcifications ( CREST)
     Advanced stages
      ◦ Claw like Fingers & auto amputation of fingertips ( auto- amputation of
        spleen seen in -?)
      ◦ Face drawn mask
     Alimentary Tract
      ◦ Muscularis -atrophy & fibrosis (MC- esophagus)
      ◦ Gastro esophageal reflux
      ◦ Malabsorption syndrome
     Musculoskeletal
      ◦ Early - Inflammation, hypertrophy and hyperplasia (synovial tissues)
      ◦ Later - Fibrosis of joints (no joint destruction -unlike RA)
     Kidneys
      ◦   Affected in 2/3rd of patients (MCC of death - renal failure)
      ◦   glomerular changes – nonspecific
      ◦   vessel wall changes- most prominent (intimal thickening &proliferation)
      ◦   Hypertension- 30% (Malignant HTN in 20%)
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    Dr.T.Krishna MD, www.mletips.co m
     Clinical Course
      ◦ Women in the 50- to 60-year age group
      ◦ Raynaud phenomenon- episodic vasoconstriction of the arteries and
        arterioles of the extremities
            Earliest & seen in all patients
      ◦ Malignant HTN - most ominous
      ◦ GI symptoms- Dysphagia, intestinal obstruction, or mal-absorption
        syndrome
      ◦ Respiratory difficulties




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    Dr.T.Krishna MD, www.mletips.co m
   Inflammatory Myopathies
    ◦ Dermatomyocytis,
    ◦ Polymyocytis,
    ◦ Inclusion-body Myocytis,
   Mixed Connective Tissue Disease
    ◦ coexistence of features suggestive of SLE, Polymyocytis,
      rheumatoid arthritis, and systemic sclerosis,
    ◦ high titers of antibodies to RNP particle-containing U1 RNP
   Poly arteritis Nodosa (PAN) & Other Vasculitides
    ◦ Necrotizing Vasculitis




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