Chronic Inflammation

Question 1

What can chronic inflammation be also called?

Answer 1

Persistent/prolonged inflammation

Here, active inflam, tissue destruction and attempts a repair are proceeding simultaneously

Question 2

Clinical features of chronic inflammation

Answer 2

Symptoms related to locality
Tiredness (systemically and non-specifically unwell)
Disease specific signs
e.g. RA, OA, syphilis, SLE, atherosclerosis, TB, sarcoidosis, scleroderma

Question 3

Lab tests for chronic inflam

Answer 3

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

Question 4

Long term effects of chronic inflam

Answer 4

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

Question 5

How does inflam cells benefit cancer cells

Answer 5

They promote increased proliferation and enhanced survival

Question 6

How does Inflammation lead to DNA changes?

Answer 6

. activated leukocytes (Mø) release reactive O2 and N species leading to mutagenesis
. cytokines include activated cytidine deaminase which causes genomic instability

Question 7

How does DNA change lead to inflammation

Answer 7

. Oncoproteins (RAS, Myc) enhance production of inflam cytokines and chemokines (IL-6,8) and attract inflam cells
. Inflam cells promote angiogenesis

Question 8

Clinico-pathological characteristics of chronic inflam

Answer 8

. 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

Question 9

List the Clinico-pathological causes of chronic inflam

Answer 9

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

Question 10

Clinico-pathological scenario (1)

persistent infections of microorgs

Answer 10

. 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

Question 11

Clinico-pathological scenario (2)

prolonged exposure to toxins

Answer 11

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

Question 12

Clinico-pathological scenario (3)

autoimmunity

Answer 12

autoantigens is self-perpetuating. Lead to hypersensitivity rx
. RA (rheumatoid nodules): granulomatous
. Lupus erythematosis (SLE): NOT granulomatous
. Scleroderma: NOT granulomatous

Question 13

What ‘s the difference between granulation tissue and granulomatous inflammation

Answer 13

• -> 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

Question 14

Pathogenesis of Silicosis

Answer 14

. 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

Question 15

Will the people infected with TB bacilli necessarily become sick with the disease? Why?

Answer 15

No.
Immune system ‘walls off’ the TB bacilli, which protected by a thick waxy coat that can lie dormant for years (Latent lesion - primary)

Question 16

What are symptoms of TB?

Answer 16

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

Question 17

What are gross features of Primary TB?

Answer 17

. Pale lesions
. millet seeds
. tubercles = granulomas
. result of haematogenous spread of bacterium to organs (dissemination)
. Not yet infectious as no bacilli in sputum

Question 18

What are histological appearances of Primary TB

Answer 18

. Central necrosis
. thick mass of proliferated Mø-derived epitheloid
. these cells fuse tgt forming giant cells
. outer most layer is CD4 and T-lymphocytes

Question 19

What does chest x-ray of primary TB look like?

Answer 19

. Small lesions caused by haematogenous spread of bacilli –> ‘ground-glass’ appearance
. Hilar lymph nodes seen as calcification

Question 20

Some main mechanisms that TB survive in alveolar Mø

Answer 20

. 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

Question 21

What’s special in Primary TB infection?

Answer 21

. Gohn focus = infection develops in periphery of lung
. Gohn complex= Gohn focus + lymph node
. it has granulomas that poorly eliminated by fibrous tissue

Question 22

What’s special in Secondary TB?

Answer 22

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

Question 23

Isolated-organ TB examples

Answer 23

. 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)

Question 24

How to find TB in a patient?

Answer 24

. 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

Question 25

Compare Mnatoux test and Quantiferon Gold test

Answer 25

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

Question 26

What happens when lose CD4 T cell function and Mø function over time

Answer 26

. Initially, HIV person become prone to TB (reactivation or infection) . Then prone to 'atypical' Mycobacteria

Question 27

Is Multi-drug resistant TB (MDR-TB) dangerous?

Answer 27

``` YES! . Esp. in former Soviet union . esp. common in HIV infection patient . requires extensive chemotherapy (2-3yrs) with second-line anti-TB drugs . expensive ```

Question 28

Key features of epithelioid cells

Answer 28

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

Question 29

How come TB has several disease manifestations

Answer 29

usually because of immuno-competency of host

Question 30

MAIN examples of chronic inflammation (must know!)

Answer 30

``` . RA --> not infectious . OA . Syphilis . atherosclerosis --> not inflam . SLE (systemic lupus erythematosus) . TB . Sarcoidosis . Scleroderma ``` note: pyogenic meningitis is not chronic inflamm