CHRONIC INFLAMMATION

Prepared by: Dr. Rasha Arafa Abd-elmaksoud

CHRONIC INFLAMMATION

•Definition: It is inflammatory process in which lymphocytes, plasma cells and macrophages predominate, and
which is accompanied by formation of granulation tissue resulting in fibrosis.
•Causes: chronic inflammation may arise in one of two ways:
(1) It may follow acute inflammation.
(2) Chronic almost from the onset
 Types of chronic inflammation:
(1) Chronic nonspecific inflammation:
Different irritants can produce this reaction so the etiological
factor can not be identified from the inflammatory reaction.
-This type follow acute inflammation e.g. chronic abscess.

(2) Chronic specific inflammation (= Granuloma):

Each irritant produces a specific inflammatory reaction and so
the etiological factor can be identified from reaction e.g.
tuberculosis, bilharziasis.
General features of chronic inflammation:
1) The irritant is mild and has a prolonged action.
2) Onset is gradual and duration is prolonged.
3) Initial tissue necrosis may not be marked.
4) Vascular phenomenon is less marked than in acute inflammation. Later on the small arteries
and arterioles show thickening and narrowing by proliferation of the subintimal connective
tissue. The change is called endarteritis obliterans.
5) Fluid exudate is not marked.
6) Cellular exudate consists of:
a- lymphocytes: main cell of chronic inflammation, change to plasma cell and liberates
lymphokines
b- plasma cells: produces antibodies.
c- Macrophages: are phagocytic cells widely distributed in tissues and include: monocytes of blood,
histiocytes of connective tissue, Kupffer cells of liver, littoral cells of spleen and Lymph nodes,
microglia in brain and osteoclasts of bone. Their functions are:
1)Phagocytosis of necrotic debris.
2)Phagocytosis of bacteria and other irritants of chronic Inflammation
3)True scavenger cells in repair
4)Formation of giant cells
d- Epithelioid cells.
e- Giant cells: formed by fusion of macrophages. The morphology of giant cells is variable. It may
be:
i- Langhan's giant cell type: when the nuclei are peripherally situated especially in tuberculous
lesions.
ii- foreign body giant type: when the nuclei are placed centrally as (F.B)foreign body. reaction.
Giant cells have a greater phagocytic power.
7) Attempts at repair is seen from the beginning and consists of capillaries and fibroblasts.
Fate:
1. Healing with effective treatment.
2. Persists, with or without acute exacerbation, and may results in several
complications as: chronic toxemia, secondary amyloidosis and even in
some sites predispose to neoplasia.
SS ACUTE CHRONIC
INFLAMMATION INFLAMMATION

irritant Mild, moderate or severe mild

Inflammatory cells Neutrophils & macrophages Macrophages, plasma cells and

lymphocytes.

Onset sudden gradual

Toxaemia Acute toxaemia Chronic toxaemia

duration Short (Days/weeks) Long (Months/years)

fibrosis Minimal or absent marked

Vascular changes marked Mild

Blood vessels Thin, dilated and congested Thick walled arteries and arterioles
capillaries (endarteritis)
Granuloma
Definition: it is chronic specific inflammatory reaction in which the histiocytes play a predominant role. It starts as tiny granules
which fuse to form tumour-like mass grossly.
Types:
(1) Infective granuloma:
a. Bacteria: e.g. tuberculosis, leprosy and syphilis.
b. Virus: lymphogranuloma inguinale
c. Parasites: e.g. Bilharziasis.
d. Fungi: Actinomycosis.
(2) Non infective granuloma:
a. Allergic granuloma: as Rheumatic fever, Rheumatoid arthritis and crohn’s disease.
b. Foreign body granuloma: around foreign bodies as beryllium, catgut, talc powder … etc.
c. Granulomas of unknown cause: as sarcoidosis
Bilharziasis (Schistosomiasis)
• Definition: It is an infective parasitic granuloma caused by Schistosoma infection which is endemic in Egypt. There are three
species: Schistosoma haematobium affects mainly the urogenital system, Schistosoma mansoni and Schistosoma japonicum affects
mainly the digestive system. Only the first two species are present in Egypt.

• Mode of infection: Cercariae (in the water) penetrate the skin reaching the capillaries and circulate with the venous blood to reach
the lungs. They pass to the systemic arterial circulation and reach different organs. Only the cercariae that reach the abdominal organs
drained by the portal blood can survive.

*They reach and liver in the intrahepatic portal branches to attain maturity to male and female worms. Adult worms move as couples
(male and females) from the liver down to the rectal plexus (S.M). S.H reaches the vesical, prostatic and utero- vaginal plexuses.
Reaching the smaller vessels, the thinner female leaves the male and passes to reach narrow sub- mucous venules and lay eggs. The
ova pierce venules to reach the peri- venular tissue. Because of muscular contractions of the urinary bladder and colon, some ova pass
with urine or stools (open lesion). The worm may live for 30 years.
Bilharzial reactions
Bilharzial lesions are allergic reactions mainly of type I (immediate) and type IV (delayed) allergy against
antigens produced by cercariae, worms, ova and autoantigens.

• I- Cercariae: Cause;

• a) Skin penetration leading to acute dermatitis.

• b) Its passage in the lungs leads to bronchopneumonia.

• M/E: The cercaria are surrounded by neutrophils and eosinophils in the tissue.
• II- Worms:

A) Living worms produce:

1. Pigments: the worms feed on the hemoglobin of the RBCs, producing haematin- like dark pigment, circulates in the blood and
phagocytosed by the RES in the liver, spleen lymph nodes and bone marrow.

2. Antigens: circulate in the blood causing RES hyperplasia as well as allergic reactions.

3. Ova (living or dead):

• The living ova are oval, red and cellular with yellowish brown thick refractile chitinous shell and spine. The dead ova are blue
(calcified) acellular and amorphous with shell. The transversely cut ova appear rounded.

a) living ova lead to bilharzial reaction in the form of:

• Venular: causing endophlebitis.

• Perivenular: causing tissue reactions which include:.

➢ Immediate allergic reaction (type I).

➢ Granulomatous reaction (Delayed hypersensitivity- Type IV) which consists of lymphocytes, plasma cells, eosinophils, macrophages, foreign body
giant cells and outer granulation tissue. The reactions is either diffuse or in the form of small nodules (called bilharziomas or pseudotubercles). The
center of the reaction may show minimal necrosis.

a) Dead ova excite mild or no inflammatory reaction.

II- Worms:

B) Dead worms produce:

• 1- Bilharzial antigen leads to RES hyperplasia.

• 2- Venular and perivenular changes in the form of immediate allergic reaction with dense eosinophilic
infiltrate (eosinophilic abscess). Such reaction is seen mostly in the liver and lungs.

III- Auto- antigens:

• These are derived from the inflammed tissue, stimulating autoantibody formation.
Bilharzial lesions
i. Solid organs: Bilharzial lesions in solid organs consists of tissue destruction and fibrosis.

ii. Hollow organs: The submucosa of the urinary bladder and intestine (rich venous plexus) is mostly involved followed by the mucosa, muscle layer
and subserosa.

➢ Early lesions:

1. Hyperaemia of the mucosa and submucosa due to immediate allergic reaction.

2. Passage of bilharzial ova through the intestinal wall to reach the lumen leading to multiple submucosal hemorrhagic spots as well as tiny mucosal
erosions.

3. Granularity due to formation of Bilharzial granulomas.

➢ Late lesions

1. Polyps formation, occurs in the following steps:

a) Granularity (small elevations) due to bilharzial reaction.

b) Epithelial hyperplasia (adenomatoid formation).

• N/E of the polyp:

• - A small polyp is sessile and simple (unbranched), as it enlarges it becomes pedunculated and compound
(branched).

• - The covering mucosa may be intact or ulcerated.

• - It is usually reddish in colour and showing haemorrhagic spots.

• - It is soft in consistency.

• M/E of the polyp:

• It is formed of a central core of connective tissue containing bilharzial granuloma.

The covering mucosa may be intact, hyperplastic or ulcerated.

2-Sandy patches: Heavy ova deposition compress the blood vessels causing necrosis in the submucosal area
containing -the ova. The area is fibrosed and the ova become dead and calcified. It compresses the overlying mucosa,
interfere with its blood supply causing atrophy and thinning of the mucosa. The calcified ova shine through it.

• N/E: Circumscribed, raised patch, rough and dirty yellow (like wet sand). Gritty sensation is felt when the patch is
sectioned with knife.

• M/E: Calcified ova with minimal or no bilharzial reaction. The surrounding tissue is fibrosed. The overlying
mucosa is atrophied and may be ulcerated.

3-Ulcers: Ulcers are common finding in bilharziasis.

• N/E: These are single or multiple, small rounded or large irregular, superficial or deep, with sharp edge, irregular
margin, granular floor and indurated base.

• M/E: The base of the ulcer shows bilharzial granulomas.

• Causes: It may be caused by passage of ova through the mucosa, allergic necrosis, twisting of the pedunculated
polyp, ischemic necrosis in the tip of a polyp, secondary bacterial infection, atrophy of the mucosa over a sandy
patch, and lastly the fissure ulcer which occurs in the urinary bladder.
4- Lesion due to fibrosis: (closed lesion). The ova deposition continue in the muscle, subserous and peritoneal
layers causing fibrosis in these sites. The organ is fibrosed and become small (contracted organ) with obstructive
syndromes.
Urogenital Bilharziasis:
It is more common in the trigone and posterior surface (rich blood supply).
1. The bladder lesions differ from the last description in:
• - The polyp are few in number, not more than two and small in size.
• - Sandy patches are common.
• - In closed lesions the bladder capacity decreases and the peritoneum shows small nodules.
• - Ulcers take many forms, especially linear (fissure) ulcers.
• - Epithelial changes are found; these are due to bilharzial reaction and secondary bacterial infection.
These epithelial changes:
• a- Hyperplasia takes the form of:
• - Focal increase in the epithelial thickness.
• - Dipping down of the hyperplastic epithelium.
• b- Brunn’s nests: These are cellular masses formed of the dipped cells that are separated from the surface
epithelium. Degeneration in the central cells of the masses produces cystitis cystica and/or cystitis glandularis.
 c- Cystitis glandularis d- Cystitis cystica

- small size. - large size.

- Lined by 1-2 layers of columnar cells. - Lined by 1-2 layers of flat cells.

- contains mucus. - contains watery secretion.

- It is precancerous. - It is not precancerous.

e- Atrophic changes over the sandy patches

f- Squamous metaplasia (leukoplakia):

These are irregular patches of whitish colour. They are thick,

opaque and formed of keratinized stratified squamous
epithelium. They are precancerous.
Complication of urinary bilharziasis:
1. Microcytic hypochromic anaemia which is due to repeated haematuria caused by ulceration..

2. Stone formation caused by secondary bacterial infection of bladder wall (alkaline urine).

3. Obstructive uropathy which is caused by polyps and bladder fibrosis.

4. Carcinoma of the bladder.

5. Pulmonary bilharziasis.

• Other urogenital Bilharziasis:

1) Bilharziasis of the ureter: common in the lower third and the lesions are more or less like that of the bladder. The complications here are also like that of
the bladder.

2) Bilharziasis of seminal vesicles cause tissue destruction with haemospermia.

3) Bilharziasis of prostate cause bladder neck obstruction.

4) Bilharziasis of testicle leads to hydrocele.

5) Bilharziasis of spermatic cord leads to diffuse thickening.

6) Bilharziasis of urethera cause stricture

Intestinal Bilharziasis
1- The ova deposition is commonest in the rectum and sigmoid colon, gradually decreasing as the small intestine
is approached.

2- The intestinal lesions differ from that described in the following:

- The polyp are numerous and large.

- Sandy patches are few or even absent due to lesser number of ova.

- In closed lesions, the peritoneum shows large pericolic mass and the intestinal lumen is narrowed.

- Ulcerations are common while fissure ulcers are absent.

Complications of intestinal bilharziasis
1. Bilharzial dysentery.

2. Microcytic hypochromic anemia which is due to repeated bleeding caused by ulceration.

3. Chronic intestinal obstruction which is caused by fibrotic stenosis or polyps.

4. Abnormal peristalsis with intussusception caused by bilharzial polyps.

5. Bilharzial hepatic fibrosis.

6. No relation to malignancy.
 Tuberculosis
Definition: chronic infective granuloma affecting nearly all body systems mainly the lungs.
•Predisposing factors:
• A) Environmental:
• Low socioeconomic standard.
• Bad general hygiene.
• Contact with tuberculous persons.
• Overcrowding.
• Environmental pollution.
• b) Personal factors:
• Negroes (more than white persons)
• Malnutrition
• Debilitating diseases (as D.M)
• Immune deficiency states
Causative Agents:
T.B. bacilli are aerobic, acid- fast, non- motile, not produce exotoxins or endotoxins, and carried by
macrophages.

• Structure o f T.B. bacilli:

• Carbohydrate, lipid and protein (tuberculoprotien).

• Types of TB Bacilli:

1. Human type (Mycobacterium tuberculosis) causes infection by inhalation.

2. Bovine type (Mycobacterium Bovis) causes infection by ingestion.

 Primary tuberculosis
(Childhood type)
Occur in young ages, non-immunized persons.

Methods of infections:

1) Inhalation. 2) Ingestion 3) Direct contact.

Site of primary complex:

1- lung. 2- Intestine 3- Tonsils 4- Skin 5- Nose (rare site).

The constituents of primary complex: it consists of 3 elements:

1. Parenchymatous lesion (tubercle in affected organ).

2. Tuberculous lymphangitis from the draining parenchymatous area to lymph node. It forms a cord of multiple tubercles in the
whole course.

3. Tuberculous lymphadenitis: T.B. of lymph nodes draining the area of infection.

 Fate of primary complex:
1- Good fate:
a. Healing:
- Small lesions heal by fibrosis leads to small fibrous scar.
- Large lesion undergoes calcification & encapsulation or cavity formation with epithelialization.
b. The organism may die or remain dormant in the healed lesion.
c. A state of cell mediated immunity and hypersensitivity is acquired for a period.
2- Bad fate (spread):
a. Local.
b. Lymphatic.
c. Hematogenous spread.

d. Natural passage.
 Secondary tuberculosis
Adulthood type
Methods of infection:

- Endogenous by reactivation of dormant focus.

- Exogenous by inhalation or ingestion.

Sites:Any site, mainly the lung & intestine are affected.

Pathogenesis: Because of primary infection or BCG vaccination, the patient usually acquires immunity and
hypersensitivity. The immunity protects the patient for some time while hypersensitivity usually affects the
proliferative reaction of secondary tuberculosis.

Reaction of the body against bacilli in secondary infection: It is of two types:

1. Proliferative reaction in solid organs.

2. Exudative reaction in serous sacs and sometimes in soft parenchymatous organs.

1-Proliferative reaction of secondary TB
The difference between proliferative reaction (tuberculous follicle) in secondary than primary infection are:

*The reaction is extensive, exaggerated, and rapid to occur with more caseation. The caseation material is more
in amount, soft and can be liquefied and discharged through natural passage or skin forming ulcer, sinus, or
fistulous tract. Proliferative reaction in primary T.B. Proliferative reaction in Secondary T.B.
Slow occurrence, firm & well formed. -Rapid occurrence, softer, with more liquefaction
leading to cavitation, sinus, fistula or ulcer
formation discharging tuberculous caseous
material.
Late & less important spread through natural - Spread through nature passage is rapid and
passage. easier.
Blood spread (Hematogenous) is more rapid - Blood spread is less than primary.
than secondary & fatal.
Lymph nodes are enlarged & form a part of the - No lymph node enlargement.
complex.
•Hallmark is necrotizing granulomatous inflammation,
composed of central necrotic zone surrounded by
epithelioid histiocytes with varied number of
multinucleated giant cells and lymphocytes
•Multinucleated giant cells may contain Langhans type
giant cells (nuclei arranged in a horseshoe shaped pattern
at the periphery of the cell) but Langhans type giant cells
are not specific for TB infection
•Organisms are usually present within the central zone of
necrosis, seen on special stains (in some cases)
•Nonnecrotizing granulomas can be present as well
II- Exudative Reaction:
• Occur in serous coverings but sometimes in lung parenchyma. The serous covering becomes studded with
excessive number of tubercles with associated exudate. The exudate may be:

• - Serous. - Serofibrinous. - Caseating material.

• The exudate contains lymphocytes, macrophages and caseating material. The lymphocytes represent 70% of
the inflammatory cells. It is usually associated with absent or little mesothelial cells.
Fate of secondary T.B.
• 1- Good fate:

• Healing, fibrosis, calcifications encapsulation, cavity formation with epithelialization.

• 2- Bad fate: Extension and spread:

- Local.
- Natural passages: more important than in primary.
- Blood (rare): less than the primary.
- Lymphatic: no lymphatic spread.
B) Bad Fate (progressive lesion):
• I- cavitary Tuberculosis:
• Softening and liquefaction of caseating material of the apical and subapical lesion with expectoration and cavity formation. The cavity may
heal or pass to:
• II- Chronic fibrocaseous cavitary tuberculosis:
• It occurs with higher dose and moderate resistance. It extends for many years.
• Pathogenesis and N/ E:
a) The lesion extends from the apical focus to adjacent bronchial wall and lung tissue. The caseous material becomes discharged through
bronchioles leaving a mother cavity with irregular thick wall and surrounded by fibrous tissue. The lining is irregular shreddy and yellowish
due to caseous material, with raised areas due to thickened blood vessels and bronchioles.
b) The caseous material extends through bronchioles and alveoli results in formation of small caseous areas when evacuated acinar cavities and
formed (daughter cavities). Usually the mother is the largest one and daughter (acinar) cavities extend from apex to base of the lung.
c) Fibrosis as a trial for healing extends in between the cavities with resultant shrunken lung and bronchiectasis.
d) Foci of caseation in the w.
e) all of blood vessels cause aneurysm formation when rupture severe fatal hemoptysis occurs

• M/E:

• Extensive caseation necrosis formed from multiple caseating tubercles. Healing by fibrosis, epithelialization of cavities, and
calcification may occur.