Acute and Chronic Inflammation Flashcards
(33 cards)
1
Q
Cardinal Signs of Inflammation
A
- Reddening & Increased heat (due to ↑ blood flow),
- Swelling (due to exudate),
- Pain (due to inflammatory mediators & compression of local nerves),
- Loss of function
2
Q
Causes of Inflammation
A
- Microorganisms & parasites: parasitic pneumonia (lungworm)
- Trauma: mechanical, chemical and thermal insult
- Aberrant immune responses: hypersensitivity & auto-immune disease
- Malignant neoplasms: chemical mediators (matrix metalloproteinases) breaks down ECM
3
Q
Classification of Inflammation
A
- Divided into two categories: acute and chronic but with some overlap - important to appreciate this
- Acute - sudden onset & lasts hours- days; vascular, humoral and cellular alterations–> 5 cardinal signs
Sequelae:
1. Death
2. Resolve by regeneration in association with host defence mechanisms, (which may be assisted by therapeutic measures)
- *3. Undergo repair by fibrosis - certain tissues (e.g. neurons)**
- *4. Become chronic** (goes through a subacute phase first), depending upon the persistence of the agent and the amount of damage its inducing
4
Q
Stages of Acute Inflammation
A
- Vascular Phase
- Exudative Phase
- MIgration of Leukocytes
5
Q
Vascular Phase
(Acute Inflammation)
A
- Initial phase= transient (secs) -arteriole constriction (‘white line’) - smooth muscle response
- Hyperaemia(x-cess of blood in vessels)= (mins - days) vasodilation will occur, increasing arteriole diameter and opening new capillary beds –> ↑ blood flow (gives reddened appearance to tissues)
- Stasis-(<30mins) After vasodilation, blood circulation slows down –> leukocytes margination
6
Q
Exudative Phase
(Acute Inflammation)
A
- Endothelial Contraction – The endothelial cells of venules are forced to contract by chemical mediators (e.g. mast cells –> histamine), forming a gap between the cells–> ↑ vascular permeability–> escape (exudation) of protein-rich fluid from blood into surrounding tissue
- Opening the tight junctions (intercellular junctions)
-usually impermeable to cells at this junction. This vessel becomes ore permeable. By histamine through mast cell!
Ability of fluid containing protein to leave the circulation
- Key is the MAST CELL- also important in opening the pre-capillary sphincter
- Other causes: Physical damage, Toxic agents, Infection, Enzymes, Oxygen free radicals
- Fluid exudate: Water & electrolytes, Plasma proteins (albumin, globulin, fibrinogen), RBCs, Platelets
7
Q
Migration of Leukocytes
(Acute Inflammation)
A
- Margination: Movement of leukocytes out of blood stream–> site of injury, induced by stasis
- Expression of adhesion molecules (e.g. selectins, integrins) on leukocytes & endothelium
- Allow them to roll along the endothelium & enter the tissue
- Chemotaxis: Leukocytes are moving towards the site of insult
- Neutrophils move along a chemotactic gradient at ~2mm/ hour macrophages= slower
- Chemotaxins attract & activate leukocytes (bacterial products, degredation products (contributes to gradient), endotoxins, cytokines etc)
- Emigration via Intercellular Junctions:
- Motile cells force an opening
- Basement membrane is breached (by collagenases etc)
8
Q
Neutrophils
(Cells of Acute Inflammation)
A
- Formed in bone marrow- Production time 7 days
- Half-life in blood 6 hours- Replaced twice a day
- Once they enter the tissues do not return to the blood
- Most are lost through the mucous membranes of the body i.e. gut, urinary and respiratory tract
- Contain multi-lobed nuclei and are indistinctly granulated
Functions:
- Phagocytosis of microorganisms, tumour cells and foreign material and fusion of phagosome with lysosomes to kill/ degrade material
- Secretion and/or release of granules (cytokine/ reactive oxygen species)–> exudate to enhance acute inflammatory response- but non- specific response–> collateral damage
Recruitment:
- Neutrophils marginate in small veins (venules) & capillaries
- Loosely stick to walls, & roll along (as they’re binding & detaching to selectins)
- At junction between endothelial cells, migrate out–> site of damage
9
Q
Eosinophils
(acute Inflammation)
A
- Formed in the bone marrow, have a similar life span to neutrophils
- When there’s large number of eosinophils in a tissue, as with parasitic condition –> greenish colour
- Contain multi-lobed nuclei and distinct granules in the cytoplasm
- Are prominent in parasitic infections, and local allergic reactions [IgE]
10
Q
Mast Cells
(Acute Inflammation)
A
- Heavily granulated mononuclear cells found in tissues
- Tissue lifespan 4-12 weeks depending on location
- Degranulate in tissue injury, releasing histamine, heparin, and 5-hydroxytryptamine (serotonin) –chemical mediators of vasodilation, chemotaxis and pain
- Critical in initiation of acute inflammatory response
11
Q
Basophils
(acute inflammation)
A
- Also formed in the bone marrow
- Multilobed nucleated cells with large bluish granules in the cytoplasm
- Granules similar to those of both neutrophils and mast cells
- Thought to act like mast cells to be important in IgE mediated injury to tissues (allergic disease
- Allergies - rarely associated with disease in animals
12
Q
Systemic Response: Pyrexia
A
Pyrogens - act on the temperature control centres in the hypothalamus of the brain–> ↑ body temperature
- Neutrophils - prime source when they begin to phagocytose, also eosinophils and macrophages
- Cell walls of Gram-negative organisms, necrotic tissue, antigen antibody complexes & tumours all can potentially release pyrogens
13
Q
Functions of an Inflammatory Effusion
A
- Dilutes the toxic agent
- Protein components may contain antibodies ( IgG) - which attack/ coat (opsonise) the irritant and facilitate phagocytosis by neutrophils and macrophages
- May contain fibrin which immobilises the irritant
- It is also chemotactic to neutrophils, bringing more of these cells into the injured area
- Will wash away the irritant - if on a surface, e.g. skin and alimentary tract
- Will also bring the irritant via the lymphatic vessels to the local lymph nodes -for further processing or antigen presentation
14
Q
Serous Inflammation
A
e.g. caused by vesicular/ allergic diseases
- Due to mild vascular injury in an organ/ vessels underlying a surface
- Produces a clear to cloudy fluid with little protein present
- Vesicles of the skin produce a serous fluid; many inflammations in joints are serous
Sequel
- resolves when the irritant is overcome, or may progress to a more serious reaction
15
Q
Catarrhal Inflammation
A
- This is a mild form & occurs on mucous membranes with goblet cells and/or mucous glands
- Varies from watery to gelatinous in consistency and cloudy to pinkish in colour
- Essentially composed of sloughed epithelium, mucus, neutrophils, some RBCs, and flecks of fibrin
- Common in mild forms of rhinitis, tracheitis, bronchitis, gastritis and enteritis (forms of inflammation)
16
Q
Fibrinous Inflammation
A
- Due to more severe endothelial injury resulting in the escape of fibrinogen from the blood and conversion to fibrin
- Is a yellowish coagulum on the surface of a tissue or within it
- Is common in lungs and on serous surfaces (e.g. thoracic, pericardial and peritoneal)
- In hollow organs, it may coagulate within the lumen, forming a cast
- It will peel off from the underlying tissue easily (in contrast with fibrous adhesions)
Sequel - Fibrinous exudates may also resolve if the fibrin is digested by macrophages
- In pleural, pericardial and peritoneal cavities, organisation of the fibrin fibrous tissue may occur producing more permanent adhesions between visceral & parietal surfaces pain & loss of function
17
Q
Diptheritic Inflammation
A
- A more severe form of fibrinous exudate- repairs by scar formation
- Firmly adherent to the underlying tissue: attempts at removal cause tearing of this tissue
- Commonly seen with internal surface fungal infections e.g. nose of the dog and guttural pouch of the horse, fungal toxins penetrating the underlying tissue causing coagulative necrosis
- Can be very haemorrhagic
Sequel- repair by scar tissue
18
Q
Haemorrhagic Inflammation
A
- A severe acute to peracute inflammation in which haemorrhage is the main component:
- Seen in the lymph nodes, lungs and intestine in severe inflammation but can occur in all tissues
Sequel - if widespread, is most commonly associated with acute deaths e. g. acute viral, bacterial or toxic diseases - if strictly localised, e. g. bruising, then it may repair
19
Q
Purulent (suppurative) Inflammation & Abscess Formation
A
- Where pus (mix of dead & dying neutrophils, necrotic cells & a pyogenic agent) is the predominant feature;
- Proteolytic enzymes released by the dying neutrophils lyse tissue cells producing a fluid
- Colour varies - white, yellow, green, brown - depending upon the agent
Sequel- resolution of abscesses depends on their location
- If near to a surface, will rupture onto it–> beneficial as it discharges to the exterior with or without the pyogenic organism
- Detrimental if rupture–> body cavity- in deeper tissues–> extensive fibrous capsule formation
20
Q
Deleterious Effects of Inflammation
A
- Local tissue swelling (e.g. laryngeal oedema in acute laryngitis)
- Local tissue damage due to inflammatory cells or their products
- e.g. in recurrent airway obstruction in horses, alveolar walls are damaged by proteases from neutrophils
21
Q
Lympocytes
(Chronic Inflammation)
A
- Formed in BM- Circulate between the blood, tissues & lymphatic system
- Life span up to 200 days
- Round cells with a densely staining nucleus and a thin, often indistinct, rim of cytoplasm
- Various types similar in appearance but differ in function – distinguish by immunohistochemistry
- T cells: CD3 antigen, B cells: CD79a antigen- targeted by tagged antibody–> brown staining
22
Q
Plasma Cells
(Chronic Inflammation)
A
- Derived from B-lymphocytes (produce Ab) at the area of tissue damage
- Presence in tissue indicates body is producing a humoral response against an antigen
- Round- oval shaped cells, eccentric round nucleus & abundant plum/purple cytoplasm
- Activated plasma cells with abundant immunoglobulin (reddish globules in cytoplasm)= Mott Cells
23
Q
Macrophages
(Chronic Inflammation)
A
- Form from monocytes
- Large round cells, central- eccentric round nucleus & abundant clear, often vacuolated (foamy) cytoplasm
- Normally present in tissues as fixed histiocytes e.g. sentinel macrophages in the lung
- In inflammation, most are derived from circulating monocytes which leave blood vessels tissue
- Functions: Phagocytosis, antigen presentation & stimulation of fibroplasia and fibrosis
- Can accumulate due to:
- Inability to lyse irritants (foreign material e.g. glass embedded)
- Antigen-antibody complexes forming around pathogens–> ‘tissue grains’
- Survival of infectious agents within macrophages (e.g. acid-fast bacilli)
Subtypes:
- Epithelioid cells
- Look like squamous epithelial cells- pink cytoplasm & indistinct borders
- May be binucleate
- Primarily secretory rather than phagocytic
- Giant cells
- Multinucleated (several hundred) cells formed by the fusion of
macrophages or epithelioid cells
24
Q
Granulomatous Inflammation
A
Type of chronic inflammation, usually caused by ↓ virulence but persistent organisms or by foreign bodies
Microscopic Structure of Granuloma
- Central core containing agent or irritant
- Surrounding chronic inflammatory cells:
- Macrophages= main effector cell (often as ‘epithelioid’ cells) & lymphocytes & plasma cells
- Eosinophils in parasitic granulomas
- Necrosis in mycobacterial and fungal granulomas
- Calcification in mycobacterial granulomas in some species
- Outer fibrous tissue capsule
Bacterial Granulomas
- Actinomyces bovis (lumpy jaw)- in cattle, commensal of oral cavity but enter bone due to trauma tissue grains- stimulates influx of macrophages
- Mycobacterium tuberculosis- survive within macrophages
Parasitic Granulomas
Muellerius capillaris: sheep lung, Filaroides osleri: dog trachea
25
Stages of Tissue repair
1. **Removal** of necrotic debris (phagocytosis)
2. **Angiogenesis**- Ingrowth of immature blood vessels (granulation tissue forms in defect)
3. **Fibroplasia**- Production of immature scar tissue
4. **Fibrosis**- Production of mature scar tissue- as strong/ stronger than original tissue
26
Cells of Repair
* **Fibroblasts** - derived from local connective tissue cells & involved in the organisation of damaged tissue **(fibroplasia)**
* **Endothelial Cells** - in conjunction with fibroplasia there is a proliferation of the vascular endothelium into the organising tissue **(granulation tissue)**.
27
Granulation Tissue Formation
* Vascular connective tissue:
**-Capillary loops**
**-Fibroblasts** - collagen production
**-Leukocytes**- granulocytes & macrophages (to a lesser degree now)
* Extremely **resistant** to infection
* Supports **migration** of epithelium to cover the defect
* Its **contraction** reduces the amount of tissue to be replaced
* Forms at sites of skin injury if large areas of epithelium are lost
* Forms the lining of sinus tracts discharging from deeper lesions
* Common example: formation of **excessive** granulation tissue on
* the **legs of horses** with poorly healing wounds - **'proud flesh'**
28
Factors Affecting Healing
**The ability of the species to cope with that particular inflammation**
* **Peritonitis**: In the ox can be walled off, in the horse is usually fatal
**The age of the animal**
* **Younger** animals being more successful than older animals
* But immune system **immature** e.g. Pseudorabies virus (porcine herpes virus)= ↑ fatal in pigs \<3weeks
**The nature of the tissue damaged**
* Highly specialised tissue (CNS) rarely repairs successfully unless the injury was mild (e.g. fibrocartilaginous embolism in the spinal cord of dogs)
**The amount of tissue damaged**
* If the functional reserve of the damaged tissue has been exceeded, signs of disease related to this insufficiency will occur
**If there is substantial fibrosis in the tissue**
* Progressive destruction of the normal tissue adjacent to the fibrous tissue as it matures and contracts- interferes with vascular supply to the area
- The liver in cirrhosis (ragwort poisoning in cattle/ horses)
- The kidney in chronic renal disease (cats)
29
Regeneration vs. Repair
* **Repair**- damaged tissue= replaced by granulation tissue fibrous scar tissue, **doesn’t retain functional characteristics of the tissue that it has replaced**, functional impact depends on how much is replaced
* **Regeneration** is the process of replacement of damaged tissue by n**ormal tissue of the same type- functional status of the tissue is restored.**
***Tissues are divided by their ability to regenerate normal structure:***
1. **Labile**
2. **Stable**
3. **Permanent**
30
Labile Tissue
- Constantly replenishes its tissue cells throughout life
- Skin & mucous membranes which normally desquamate their outer layer of cells during life
- Bone marrow and fat are other examples
31
Stable Tissue
- Has limited ability to replace itself, retaining the capacity to replace cells that have undergone necrosis ***e.g. liver, some endocrine glands and renal tubular epithelium***
- Or having the ability to respond to greater need for their function in the body ***e.g. skeletal & smooth muscle***
32
Permanent Tissues
- It has poor or no regenerative capacity: highly specialised tissues whose cells generally have only one function
- ***E.g. Neuronal cell bodies*** in the central nervous system, t***he retina of the eye***, and the cells responsible for hearing in the ear, ***cardiomyocytes*** (repair by fibrosis/ fat replacement)
- _Axons in the peripheral nervous system, when severed, can regenerate to a limited extent_
33
STAGES IN SKIN WOUND HEALING (HEALING BY FIRST INTENTION)
**1. Haemostasis**
* Blood escapes from damaged blood vessels & fills defect- platelet degranulation \> mediator release
* Fibrin clot loosely binds the edges & dries to form a surface scab
**2. Inflammation**
* Acute inflammation develops & within 24hrs adds exudate to the site
* Inflammatory cells produce enzymes which begin to **degrade the clot & remove debris**
* Macrophage products promote repair
* Fibrin & fibronectin network provides stability and framework for cell migration
**3. Repair**
* Epithelial cells start to regenerate & bridge gap within 48hrs
* Blood vessels re-grow & may form a small amount of granulation tissue
**4. Consolidation/Reconstruction**
* Final scar is small and inconspicuous
* Sufficient tensile strength for suture removal 7-10d
