Acute Inflammation 1&2

What is Acute Inflammation ?


Acute inflammation is a local response by living tissues to tissue injury resulting in the accumulation of fluid rich in protein and cells ( Polymorphs and later Macrophages)


Name the Phases of Acute Inflammation:


  1. Vascular Phase
  2. Cellular Phase
  3. Generally resolution or Suppuration

Describe The Phases of Acute Inflammation

Vascular Phase


  1. Vascular phase has a transient or brief vasoconstriction (neuronal reflex)


  1. Blood vessels then undergo vasodilation ( increase in diameter)


  1. The vasodilation and the release of Prostaglandins then increases the blood flow ( aka HYPERAEMIA) to the infected area.


  1. Afterwards, the blood flow will become slow in the distended blood vessels.
    Why ?

4.1 Due to an increase in permeability of blood vessels.


4.2 Loss of axial flow due to the exit of protein rich fluid into tissues. (exudate)



  1. Increased lymphatic flow. 
                  *Definition*
  1. Active Hyperaemia is an increase in blood flow through the tissues as a result of dilation of existing and opening up additional channels due to the effect of Prostaglandins.


  1. Passive Hyperaemia is relative stasis of the blood within the tissues resulting from a rise in venous pressure.


  1. Exudate is excess fluid in tissues or body spaces which contain plasma proteins including fibrinogen (formed as a result of inflammation)


  1. Transudate is excess fluid in the tissues or body spaces which is an ultra-filtrate with little or no protein.

Cellular Phase


There are 2 main cells types in Acute Inflammation:


  1. Neutrophils (Polymorphonuclear Neutrophilic Granulocyte)


  1. Macrophage/Histiocyte ( Mononuclear Phagocyte)

What are the Major( or Cardinal) Clinical Signs of Acute Inflammation as a Result of the Vascular Phase ?


  1. Rubor (Redness) due to vascular dilation and increase in blood flow.


  1. Calor (Heat) due to Hyperaemia or an increase in blood flow.


  1. Turgor (Swelling) due to fluid exudate.


  1. Dolor (Pain) due to pressure from the swelling.


  1. Loss of function

Neutrophil (Polymorph)


  1. Neutrophil is the most definitive cell of acute inflammation.


  1. It is produced in the BM and circulates in the blood stream (neutrophils and eosinophils are termed Polymorphs because of their lobulated nuclei).


  1. Cytoplasm of a neutrophil contains numerous lysosomes.

Function of Neutrophil


  1. The function of neutrophils is initially phagocytosis of micro-organisms and other small particles.


  2. And it only survives for a few hours after emigration.

Macrophage


  1. Macrophage are not directly produced in the BM.


  1. Initially, the stem cells leave the BM and become monocytes.


  1. The monocytes enter the blood stream and become Macrophages. Macrophages are named according to their location in the body.


  1. Monocytes in the blood are part of a widely distributed system known as "Mononuclear Phagocyte System".


  1. Macrophage are released after Neutrophil.

Function of Macrophages:


  1. Phagocytosis of small and large molecules and debris.


  1. Presentation of antigen in the lymphocyte system for antigen synthesis.


  1. Secretion of factors which stimulate Fibrosis.


  1. Production of some components of the complement.

Describe the 7 Components of the Cellular Phase


  1. Reduced flow of blood due to fluid loss.


  1. Leukocyte margination to periphery of blood stream.


  1. Triggering/ Activation of Integrins.


  1. Strong adhesion of neutrophil to endothelial cell membrane proteins. (proteins help neutrophil to change shape in order to fit through endothelial cells when going to area).


  1. Motility - also known as diapedesis which is the movement of neutrophils from the bloodstream through the intact cells of the capillaries. Chemotaxis.


  1. Phagocytosis of the pathogen, accompanied with Opsonization and Pseudopodia.


  1. Intracellular killing by enzymes and low pH.

NOTE: Neutrophil at the end of its life cycle will release Cytokines in order to stimulate the production of more Neutrophils. Creating a viscous cycle.

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What are The Consequences of Acute Inflammation ?

What are the Systematic Effects of Acute Inflammation ?


*Always happen irrespective of area affected.

List the Beneficial Effects of Acute Inflammation


  1. Dilution of toxins
  2. Delivery of Antibodies.
  3. Fibrin barrier to spread of infection.
  4. Promotion of Immunity
  5. Phagocytosis
  1. Fibrosis occurs as part of the repair of tissue necrosis by organization of excess fibrin in the exudate as part of chronic inflammation.
  1. Suppuration: Suppuration is the discharging of pus.

A severe local toxic injury with tissue necrosis caused by pyogenic organisms.
The intense emigration of Polymorphs produces an inflammatory exudate called "pus" containing:


  1. Dead tissue cells
  2. Dead or dying polymorphs
  3. Bacteria
  4. Protein(fibrin)- rich fluid containing cholesterol, fats, nucleic acids.

When suppuration occurs in solid tissue it forms an abscess. Necrosis and abscess promote the multiplication of bacteria.


Abscess increase in size or forces itself along tissue plane of lower resistance.

  1. Resolution: Is the return to normal with no morphological change. This requires that there be no damage to the supporting structure of the tissue.

Superficial Epithelium can be replaced, but the supporting stroma can NOT have been damaged.
If it is damaged, it is followed by Fibrosis.

  1. Progression: Progression to chronic inflammation if not stopped.
  1. Death

Fever


Fever is the elevation of the internal body temperature above the normal 37 degrees Celsius.


What is Fever Cause by ?


Fever is caused by the action of Pyrogen on the thermo-regulator centre in the Hypothalamus.


And probably the act on the thermo-regulator centre via Prostaglandin E.


Differentiate between the types of Pyrogens:


  1. Endogenous Pyrogens are released from Polymorphs and Macrophages stimulated by the following:

1.1 Antigen/Antibody complexes
1.2 Bacterial endotoxins
1.3 Certain viruses
1.4 A pyrogenic lymphokine from lymphocytes.


  1. Exogenous Pyrogens which include contaminants in IV infusions.

What are the ill effects of fever ?


The effects of fever include:


  1. general malaise and anorexia
  2. Increased metabolism
  3. Thermal injury to neurons at increased temperature (>41.5)

Leukocytosis


What is Leukocytosis ?


Leukocytosis is an increase in the number of leukocytes in the blood stream.


Differentiate between mature and immature neutrophils:


  1. Mature Neutrophils are available the attached to the endothelium as a certain proportion of neutrophil cells within the bone marrow.


  1. Immature neutrophils are available by stimulation of proliferation of precursors in bone marrow which may result in immature forms entering the circulation.

These are termed 'left shifted'.


NOTE: Immature neutrophils are released when there are too many mature neutrophils.


  1. Polymorphs are released from marginated pool by exercise and epinephrine.


  2. Polymorphs are released from BM by neutrophil releasing factors such as C3 Fragments.

Alteration in Serum Proteins


This results in an increase in gamma globulins (antibodies) and fibrinogen.

What The Specific Pattern of Acute Inflammation ?

Suppuration


What is Suppuration ?


Suppuration is pus formation and is usually an acute inflammatory response.


There can also be chronic suppurative inflammation with continued tissue destruction, pus formation and fibrosis.


Suppuration in solid tissue results in abscess formation.


Organisms that give rise to suppuration are called Pyogenic.

Cellulitis (Phlegmon)


What is Cellulitis ?


Cellulitis is a diffuse inflammation of the connective tissue which is caused by bacteria that produce factors that allow it to spread.


Eg: Haemolytic Streptococci which produces the enzyme, Hyaluronidase that breaks down the ground substance of connective tissue, called Hyaluronic Acid.

Pseudomembranous Inflammation


What is the Pseudomembranous Inflammation ?


Pseudomembranous Inflammation is caused by a bacteria that is attached to the surface of the mucous membrane and has little ability to invade.


& produces endotoxins that cause SUPERFICIAL necrosis.


What does the Exudate of Acute Inflammation contain ?


The exudate of acute inflammation mixed with dead tissue form a false membrane containing:


  1. Fibrin and necrotic tissues cells
  2. Casual bacteria
  3. Neutrophil and red blood cells

Serous Inflammation


What is Serous Inflammation ?


Serous Inflammation is manifested(demonstrated) by an excess fluid exudate.


It often involves the serous lining of a body cavity with fluid accumulation in the cavity. eg: pleural, peritoneal, pericardial etc.)


NOTE: The fluid is a protein-rich exudate ( which transudate in preformed cavities formed for different reasons.) and there is usually deposition of fibrin on the serous surface (fibrinous exudate).


Serous inflammation maybe acute or chronic.

Catarrhal Inflammation


What is Catarrhal inflammation ?


Catarrhal inflammation is the inflammation of the mucous membrane.


There is an addition excess secretion from local mucous gland.


Eg: common cold (upper respiratory tract)
Influenza (bronchi0

Ulceration


What is Ulceration ?


Ulceration is the loss of the surface epithelium ( eg: skin, mucosa of the gut etc.) from any cause.


Because it is on the surface, the necrotic tissue is lost.


An inflammatory response is present in the underlying stroma which maybe acute or chronic.