1.
Viral Damage to Tissues and Organs
a.
The severity of disease in humans is not necessarily correlated with the
degree of cytopathology produced by the virus in vitro.
b.
Many viruses that are cytocidal in cultured cells generally do not
produce clinical disease, e.g. enteroviruses, which cause severe cytopathic
effects (CPE) in cultured human cells, usually cause inapparent infections.
c.
Conversely, some viruses, such as the rabies virus, are noncytocidal in
vitro but cause a lethal disease.
d.
When damage to cells does impair the function of an organ or tissue, this
may be of minor importance in muscle or subcutaneous tissue, but of great
importance in key organs such as the heart or brain.
e.
Direct damage by Cytocidal viruses:
i.
direct damage to cells caused by a highly cytocidal virus.
ii.
distribution of paralysis in a patient with poliomyelitis is a direct
consequence of distribution of motor neurons of spinal cord that are destroyed
by the virus.
2.
Damage to the Epithelium of Respiratory
tract
a.
Respiratory viruses initially invade and destroy just a few epithelial
cells, but they initiate a lesion which can be progressively damage the
protective layer of mucus and lay bare more and more epithelial cells.
b.
As viral replication progresses, large numbers of progeny virions are
budded into the lumen of the airway.
c.
Early in infection, the beating of cilia, the primary function of which
is to cleanse the respiratory tract of inhaled particles, may actually help to
move released progeny virus along the airway, thereby spreading the infection.
d.
As secretions become more profuse and viscous, the cilial beating becomes
less effective and ceases as epithelial cells are destroyed.
e.
Complications of viral infection:
i.
bacterial superinfection, nurtured by accumulation of fluid and necrotic
debris in the airways.
ii.
infection and destruction of the lung parenchyma and the alveolar
epithelium.
iii.
blockage of airways that are so small in diameter that mucous plugs
cannot be opened by forced air movements – significant in newborn.
f.
In all of these complications there is hypoxia and a pathophysiologic
cascade that leads to acidosis and uncontrollable fluid exudation into airways.
3.
Damage to Epithelium of Intestinal
tract
a.
The principal agents causing viral diarrhea in children are the
rotaviruses; other viruses that produce diarrhea in children and adults:
iciviruses, astroviruses, certain adenoviruses.
b.
Rotaviruses infect cells at the tip of the villus and caused marked
shortening and occasional fusion of adjacent villi so that the absorptive
surface of the intestine is reduced, resulting in fluid accumulation in the
lumen of the gut and diarrhea.
c.
Infection generally begins in the proximal part of the small intestine
and spreads progressively to the jejunum and ileum and sometimes to the colon.
d.
Fluid loss in viral infections of the intestinal tract is mainly a loss
of extracellular fluid due to impaired absorption, and osmotic loss due
primarily to the presence of undigested lactose in the lumen.
e.
As virus destroys the absorptive cells there is a loss of those enzymes
responsible for the digestion of disaccharides, and loss of differentiated cells
diminishes glucose carrier, sodium carrier and Na-K-ATPase activities.
f.
This leads to a loss of sodium, potassium, chloride, bicarbonate and
water, and the development of acidosis.
g.
Hypoglycemia owing to decreased intestinal absorption, inhibited
glyconeogenesis, and increased glycolysis follow, which may lead to death if not
promptly treated.
4.
Epithelial damage predisposes to
secondary bacterial infection
a.
As well as having direct adverse effects, viral infections often
predispose epithelia to secondary bacterial infections, increasing the
susceptibility of the respiratory tract to bacteria that commensals in nose and
throat.
b.
Thus, infections with influenza virus may destroy ciliated epithelia and
cause exudation, allowing pneumococci and other bacteria to invade the lungs and
cause secondary bacterial pneumonia.
c.
Conversely, proteases secreted by bacteria may activate influenza virus
infectivity by proteolytic cleavage of the hemagglutinin.
d.
Rhinoviruses and respiratory syncytial virus damage the mucosa of the
nasopharynx and sinuses, predisposing to bacterial superinfection leading to
purulent rhinitis, pharyngitis, sinusitis, and otitis media.
5.
Immunopathogenesis
a.
There are certain diseases in which cell killing by immunologic attack
plays an important role in pathogenesis.
b.
Cytotoxic T cells are involved in the pathogenesis of hepatitis caused by
hepatitis A, B, and C viruses – damage to hepatocytes due to recognition of
viral antigens on the hepatocyte surface by cytotoxic T cells.
c.
Immune-mediated pathogenesis also occurs when virus-antibody-complement
complexes form and are deposited in various tissues – immune complexes play a
role in producing the arthritis characteristic of early stage of hepatitis B.