Chronic Inflammation Flashcards Preview

Human Disease > Chronic Inflammation > Flashcards

Flashcards in Chronic Inflammation Deck (30):

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

Increase CRP, ESR, homocysteine, ferritin, HDL
Elevate monocytes --> only lymphocytes/macrophage not granulocytes (secondary indication of inflam)
Elevate blood gluc

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)

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?

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?

. 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