Cell Injury Flashcards
What are the main chemical mediators of acute inflammation?
- vasodilation: histamine, prostaglandins (nitric oxide)
- increased permeability: histamine, leukotreines (bradykinin)
- neutrophil adhesion and chemotaxis: IL-1, IL-8, chemokines, C5a, LTB4, bacterial peptides
- phagocytosis: C3b
What is chemotaxis?
The movement along concentration gradients of chemoattractants (chemicals that induce an organism or cell, e.g. Neutrophil, to move it)
Describe the infiltration of neutrophils
MARGINATION - stasis of blood cause neutrophils to line up at the edge of blood vessels along the endometrium
ROLLING - they roll along the endometrium, sticking intermittently
ADHESION - neutrophils stick more avidly to the endometrium
EMIGRATION - neutrophils move through the vessel wall by chemotaxis. This increases their count around the site of damage
What do neutrophils do?
They phagocytise microorganism by contact, recognition and internalisation. They then fuse with lysosomes to destroy the contents. Activated neutrophils may release toxic metabolites and enzymes causing damage to the host tissue
How do neutrophils destroy phagoctyosed material?
- O2 dependent: superoxide and H2O2
- O2 independent: lysozyme and hydrolyses/ bactericidal permeability increasing protein/cationic proteins
What is an exudate?
Fluid loss due to inflammation. It has a high protein content
What is a transudate?
Fluid loss due to hydrostatic pressure imbalance, it has a low protein content. It can be due to cardiac failure of venous outflow obstruction
How is fluid lost from vessels?
Fluid flow across vessel walls is determined by the balance of hydrostatic and colloid osmotic pressure:
- Increased hydrostatic pressure - increased flow of fluid out of vessel
- Increased colloid osmotic pressure of interstitium - increased fluid flow out of vessel
What is Starling’s law?
How fluid moves across vessel walls (balance of osmotic and hydrostatic pressure)
What is hydrostatic pressure?
The pressure of blood against the vessel wall
What is oncotic (colloid osmotic) pressure?
A form of osmotic pressure exerted by proteins in a blood vessel’s plasma
What are the possible outcomes of acute inflammation?
Death
Chronic inflammation and fibrous repair
Abscess
Resolution
How does acute inflammation resolve?
Changes reverse, and vascular changes stop, neutrophils stop marginating and vessel permeability returns to normal. It occurs when there is little damage to supporting stroma, and only deficiency in cells themselves. Exudate drains to lymphatic, fibrin is degraded and neutrophils die.
This can happen because all mediators have short half lives, so may be inactivated by degradation, dilution or inhibition
How do the microscopic changes brought about by acute inflammation combat injury?
- Exudation: delivers plasma proteins to the site of injury, dilutes toxins, and increases lymphatic drainage
- Infiltration: removal of dead/foreign material
- Vasodilation: increases delivery of antibodies, O2, nutrients, cells etc.; maintains temperature
Name an inherited disorder of the acute inflammatory process
Alpha 1 anti-trypsin deficiency
Hereditary Anglo-oedema
Chronic granulomatous disease
What is alpha 1 anti-trpysin deficiency?
Inhibits release of elastase by neutrophils normally, so excessive elastase breaks down lung/liver tissue leading to lung cancer, emphysema and liver sclerosis
What is hereditary angio-oedema?
Deficiency of C1 inhibitor which normally inhibits bradykinin, which increases permeability, so leading to oedema
What is chronic granulomatous disease?
Recessive sex linked, immune phagocytes can’t form ROS, so can’t kill some bacteria and granulomas are formed in an attempt to contains it.
What systemic changes arise as a consequence of acute inflammation?
FEVER - endogenous pyogens, e.g. IL-1, TNF alpha and prostaglandins are released
LEUKOCYTOSIS - IL-1, TNF alpha produce accelerated release from marrow. Macrophages, T-lymphocytes release colony-stimulating factors, which stimulate proliferation and differation
ACUTE PHASE - decrease appetite, raised pulse, altered sleep patterns, and release of acute phase proteins like CRP, alpha 1 antitrypsin and fibrinogen. Spread of microorganisms and toxins as well as a drop in arterial pressure due to vasodilation can lead to shock
