Chronic Inflammation Flashcards
What can chronic inflammation be also called?
Persistent/prolonged inflammation
Here, active inflam, tissue destruction and attempts a repair are proceeding simultaneously
Clinical features of chronic inflammation
Symptoms related to locality
Tiredness (systemically and non-specifically unwell)
Disease specific signs
e.g. RA, OA, syphilis, SLE, atherosclerosis, TB, sarcoidosis, scleroderma
Lab tests for chronic inflam
NON-SPECIFIC
Increase CRP, ESR, homocysteine, ferritin, HDL
Elevate monocytes –> only lymphocytes/macrophage not granulocytes (secondary indication of inflam)
Elevate blood gluc
SPECIFIC
Disease’s factor
Long term effects of chronic inflam
Increase risk of cancer
- carcinoma in osteomyelitis (bone) with draining sinus, HepB and C (liver)
- adenocarcinoma in H.pylori gastritis (stomach), pancreatitis and prostatitis, ulcerative coltis and Crohn disease
Note: carcinoma denote malignant cancer. adenocarcinoma denote epithelial cancer
How does inflam cells benefit cancer cells
They promote increased proliferation and enhanced survival
How does Inflammation lead to DNA changes?
. activated leukocytes (Mø) release reactive O2 and N species leading to mutagenesis
. cytokines include activated cytidine deaminase which causes genomic instability
How does DNA change lead to inflammation
. Oncoproteins (RAS, Myc) enhance production of inflam cytokines and chemokines (IL-6,8) and attract inflam cells
. Inflam cells promote angiogenesis
Clinico-pathological characteristics of chronic inflam
. long time
. infiltrate of mononuclear cells - lymphocytic, Mø and plasma (not much neutrophils)
. tissue destruction (fibrosis)
. attempts healing by angiogenesis and fibrosis (connective tissue replacement)
. may follow acute inflam but may not, which is insidious low-grade
. often asymptomatic response
List the Clinico-pathological causes of chronic inflam
. persistent infections by foreign bodies or microorganism
. prolonged exposure to toxins
. autoimmunity
. Idiopathic
Clinico-pathological scenario (1)
persistent infections of microorgs
. TB (mycobacterium tuberculosis): granulomatous inflam with caseous necrosis (type IV delayed hypersensitivity)
. Leprosy (lepromatosis): granulomatous
. Syphylis (treponema pallidum): plasma cells - NOT granulomatous
. Fungal infections: often granulomatous
. Viruses: t-cell mediated
. Parasites: eosinophils - type I hypersensitivity
Clinico-pathological scenario (2)
prolonged exposure to toxins
. Foreign body rx
. silicosis lung disease (silica non-biodegradable): granulomatous
. atherosclerosis: lipid deposition - NOT granulomatous
Clinico-pathological scenario (3)
autoimmunity
autoantigens is self-perpetuating. Lead to hypersensitivity rx
. RA (rheumatoid nodules): granulomatous
. Lupus erythematosis (SLE): NOT granulomatous
. Scleroderma: NOT granulomatous
What ‘s the difference between granulation tissue and granulomatous inflammation
- -> Granulation tissue: healing - consisting of connective tissue, new capillaries, fibroblasts and inflam cells. Granular appearance when viewed at gross scale.
- -> Granulomatous inflammation: chronic inflam - by fusion of activated Mø, multi-nucleated giant cells and lymphocytes to minimize fibrosis/scarring. It develops into epithelioid that contains necrosis
Pathogenesis of Silicosis
. Silica dust particles deposited in the alveoli
. Mø phagocytose them
. Mø die and release cytokines
. Mø recruit and fibroblast proliferation
. Collagen depositiona nd fibrosis/ granulomata
. Type IV hypersensitivity
Will the people infected with TB bacilli necessarily become sick with the disease? Why?
No.
Immune system ‘walls off’ the TB bacilli, which protected by a thick waxy coat that can lie dormant for years (Latent lesion - primary)
What are symptoms of TB?
. bad cough (3 weeks or longer) . weight loss . dyspnea (short breathing) . intermittent fever . night sweats
What are gross features of Primary TB?
. Pale lesions
. millet seeds
. tubercles = granulomas
. result of haematogenous spread of bacterium to organs (dissemination)
. Not yet infectious as no bacilli in sputum
What are histological appearances of Primary TB
. Central necrosis
. thick mass of proliferated Mø-derived epitheloid
. these cells fuse tgt forming giant cells
. outer most layer is CD4 and T-lymphocytes
What does chest x-ray of primary TB look like?
. Small lesions caused by haematogenous spread of bacilli –> ‘ground-glass’ appearance
. Hilar lymph nodes seen as calcification
Some main mechanisms that TB survive in alveolar Mø
. prevent lysosomal discharge
. TB cell wall contains mycolic acids so can resist phagocytosis
. CD8 and T cell go to lymph node for immune response (stain blue)
Note: tubercle bacteria do not secret toxins
What’s special in Primary TB infection?
. Gohn focus = infection develops in periphery of lung
. Gohn complex= Gohn focus + lymph node
. it has granulomas that poorly eliminated by fibrous tissue
What’s special in Secondary TB?
. it is caused by reinfection or reactivation of previous sensitized host
. contagious
Isolated-organ TB examples
. Meninges (TB meningitis)
. Adrenals (formerly cause of Addison disease)
. bones (osteomyelitis)
. Fallopian tubes (salpingitis)
. Vertebrae (Pott’s disease)
. Scrofula in the cervical region - around neck (Lymphadenitis - extrapulmonary TB)
How to find TB in a patient?
. Ziehl-Neelsen stain: acid-fast bacili stained red in sputum but not specific.
. PCR: detect DNA in certain disease
. ELISpot: only if exposed (ELISpot for IFNg secreting antigen-specific T cells)
. Mantoux and Quatiferon Gold test: skin test as delayed type hypersensitivity. They are not diagnostic tests
Compare Mnatoux test and Quantiferon Gold test
They are both skin test for TB. Both do NOT distinguish active/latent/cleared infections. only tell if person needs further investigation
. Mantoux (PPD) test on skin
. Quantiferon (IGRA) test in blood
What happens when lose CD4 T cell function and Mø function over time
. Initially, HIV person become prone to TB (reactivation or infection)
. Then prone to ‘atypical’ Mycobacteria
Is Multi-drug resistant TB (MDR-TB) dangerous?
YES! . Esp. in former Soviet union . esp. common in HIV infection patient . requires extensive chemotherapy (2-3yrs) with second-line anti-TB drugs . expensive
Key features of epithelioid cells
. mononuclear phagocyte
. specialized type in granulomatous inflammation
. collection of activated Mø
. abundant in rough ER
How come TB has several disease manifestations
usually because of immuno-competency of host
MAIN examples of chronic inflammation (must know!)
. RA --> not infectious . OA . Syphilis . atherosclerosis --> not inflam . SLE (systemic lupus erythematosus) . TB . Sarcoidosis . Scleroderma
note: pyogenic meningitis is not chronic inflamm
