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Flashcards in Chronic Inflammation Deck (30):
1

What can chronic inflammation be also called?

Persistent/prolonged inflammation
Here, active inflam, tissue destruction and attempts a repair are proceeding simultaneously

2

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

3

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

4

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

5

How does inflam cells benefit cancer cells

They promote increased proliferation and enhanced survival

6

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

7

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

8

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

9

List the Clinico-pathological causes of chronic inflam

. persistent infections by foreign bodies or microorganism
. prolonged exposure to toxins
. autoimmunity
. Idiopathic

10

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

11

Clinico-pathological scenario (2)
prolonged exposure to toxins

. Foreign body rx
. silicosis lung disease (silica non-biodegradable): granulomatous
. atherosclerosis: lipid deposition - NOT granulomatous

12

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

13

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

14

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

15

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)

16

What are symptoms of TB?

. bad cough (3 weeks or longer)
. weight loss
. dyspnea (short breathing)
. intermittent fever
. night sweats

17

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

18

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

19

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

20

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

21

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

22

What's special in Secondary TB?

. it is caused by reinfection or reactivation of previous sensitized host
. contagious

23

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)

24

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

25

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

26

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

27

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

28

Key features of epithelioid cells

. mononuclear phagocyte
. specialized type in granulomatous inflammation
. collection of activated Mø
. abundant in rough ER

29

How come TB has several disease manifestations

usually because of immuno-competency of host

30

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