General Pathology
9/30/2008
Pathology of Infectious Diseases, Part I
Transcriber: Marc Vance
42:04
Slide 2: The microbiology class is focusing on the bacteria/viruses that cause infectious diseases; this
pathology lecture series will focus on the host and it response to these microorganisms, including the
lesions produced and the mechanisms by which the diseases develop.
Slide 3: Notice that the top 10 causes of death differs depending on where you live (the bolded diseases
are infectious in nature). In the USA the highest ranking infectious cause of death is Influenza (viral) and
Pneumonia (viral/bacterial/fungal), which both occupy the 7th highest (overall) cause of death. And
these are the only infectious diseases in the USA top ten. Looking at the top ten worldwide causes, the
#3, #4, and #6-8 causes are all infectious (lower respiratory infections (pneumonia), AIDS, perinatal
infections, diarrheal infections, and TB, respectively). This is basically because of the better health care
in the USA as compared to the rest of the world.
HIV isn’t on the USA top ten because it is better contained and there is better drug therapy here to help
preserve the immune system. People in the USA don’t die as much or as quickly as they used to from
HIV/AIDS, but treatment can be very expensive – which is why it is not always available in the
developing world (ex: Africa).
Diarrheal diseases are mostly related to poor public sanitation and not having clean drinking water.
Tuberculosis is a problem in other countries. Most of the USA TB cases are brought in from other
countries.
Slide 4: Getting an infection means your resistance to the causative microorganism has not been
successful. Your resistance to microorganisms is multifactorial.
Genetics plays a role. For example, people with the x-linked antibody deficiency (Bruton’s) cannot make
antibodies, causing recurrent infections with (mostly encapsulated) bacteria. Another example: cystic
fibrosis is an autosomal recessive disease in which defective chloride channels cause secretions to stay
in the lungs unable to be coughed up, acting as culture mediums for bacteria such as pseudomonas
aeruginosa.
Compromised anatomy and physiology are factors in infection. In cystic fibrosis, the lung physiology is
abnormal causing infection. In spina bifida, the bladder is not innervated and cannot be voided
voluntarily. This increases risk for urinary tract infection (the frequent voiding of the bladder is a critical
mechanism to inhibit bacteria from adhering to the urinary tract and proliferating). Diabetes related
neuropathies can also cause similar issues with bladder voiding/UTIs. Intact skin is one of the most
important defenses we have against infection and cannot be penetrated by many bacteria. However, an
IV needle placed into the skin creates an entry point for the microorganisms.
Immunocompetence – Congenital diseases, HIV, steroids for arthritis, immunosuppressants for a
transplant; all of these puts someone at risk for infection and this must be taken into account while
treating someone with compromised immunity.
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Circulatory/Ventilatory status – Similar to an IV causing a route for bacteria through the skin, an
endotracheal tube of a ventilator (which is placed due to respiratory damage/failure, ex: inhaling smoke
during a fire) provides a bypass of the mucosal immune system (ciliary ladder, secretory IgA, cough
reflex, etc) for bacteria to enter the lungs. Catheterization of the bladder is way for bacteria to enter the
body.
Any type of underlying disease that affects your overall health can cause infection risk. Hence acquiring
a good medical history is an important part of infection risk assessment.
Slide 5: A review of our body’s many innate immunity components. Compromise of these creates
infection risk.
Slide 6: A list of ways infection can enter the body.
Some important definitions:
nosocomial – an infection acquired in a health care system (hospital-acquired).
iatrogenic – coming from a physician or a procedure (examples: 1. A heart valve replacement
surgery in which the sterile field Is broken and the patient gets a blood stream infection with
subsequent endocarditis from a coagulase negative staph or viridians strep – this likely would
not have happened if the surgery was not done, 2. Steroids prescribed for arthritis causes an
infection. Here again, the treatment for one thing caused another problem.)
Slide 7: Whether or not you get a clinical infection depends not only on the host, but also on the
microorganism. Several factors relate to the organism:
Virulence – the ability of the organism to produce a pathological lesion. Related to endo/exotoxins,
attachment structures, etc.
Infectivity – the ability to establish in a host.
Pathogenicity – the ability of a microorganism to produce disease = virulence + infectivity.
For example – a lecturer with measles could easily be transferred to all of the students in the class if
they were not previously immunized/exposed. Measles very easily causes infectious lesions (high
virulence) and is easily spread (high infectivity) -> highly pathogenic.
Slide 8: Infection means the body has been invaded by microorganisms causing a tissue reaction to its
tissues and toxins (a lesion has been produced). Colonization means that a microorganism is present,
but it is asymptomatic and produces no lesions. Know the difference between these two terms.
An application of this: Streptococcus pneumoniae found in a sputum culture used to diagnose
pneumonia does not necessarily mean it is the cause of the infection – only if it is present in large
numbers. S. pneumoniae commonly causes pneumonia, but is also colonized in many people’s lungs
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without infection. Only if amounts were found above levels of the normal flora would it be called the
infectious agent.
A snakebite would be neither an infection nor colonization; it would be an intoxication (no bacteria, only
toxin). However, a secondary infection could follow if bacteria entered the body through the wound.
Slide 9: Exogenous infections are things we catch from the outside world (ex: a cold/flu caught from
someone else). Endogenous infections are “activations” of normal flora (ex: a woman with a UTI gets
antibiotics, which clears infection. However, this causes a candidiasis vaginal infection secondary to the
killing of the normal vaginal flora by the antibiotics. This eliminates other normal flora organisms that
were competing for nutrients with the already present candidiasis (yeast), which profile rates to an
infectious level. Many factors can trigger endogenous infections, anything that weakens the immune
system and/or disrupts homeostasis (see slide).
Slide 10: Extracellular pathogens elude phagocytosis through various methods and invade the tissue.
Staph aureus resists phagocytosis by producing leukocidins (enzymes that kills WBC’s before they can
phagocytose the bacteria). Cryptococcus neoformans (an opportunistic infectious agent that causes
meningitis in people with HIV) has an antiphagocytic capsule. Streptococcus pneumonia has multiple
serotypes, so antibodies to a previous serotype will not cross-react with another serotype, causing
recurrent infections.
Slide 11: Facultative intracellular pathogens don’t mind being phagocytized because it protects them
from the rest of the immune system. They have no need for capsules or toxins. They live inside
macrophages (ex: legionella). There are three main ways they survive after phagocytosis:
1. Inhibition of fusion of phagocytic vacuoles with lysosomes (Ex: tuberculosis)
2. Resistance to lysosomal enzymes (ex: salmonella)
3. They escape phagosomes and adapt to living/replicating in the cell cytoplasm (ex: listeria)
Slide 12: Obligate intracellular pathogens include all viruses, Chlamydia, Ehrlichia, and Rickettsia among
others. These must use the host cell’s metabolic machinery to replicate. Examples of host cells:
phagocyte, endothelial cell of capillary (rickettsiae), red blood cells, white blood cells (ehrlichia).
Slide 13: Other examples of microorganisms’ methods of infection:
Clostridium difficile can cause diarrhea and pseudomembraneous colitis if you take broad spectrum
antibiotics that kill the normal gut flora. C. difficile is normal gut flora also, but elimination of the
competition allows it to proliferate and produce toxins that damage colonic cells. It grows in the lumenal
mucous – hence the immune system cannot effectively reach it.
Some strains of E. coli can resist complement-mediated lysis, even if antibody opsonizes it.
Influenza virus – the only virus that regularly produces epidemics. This is due to antigenic shift and drift.
Each year the flu shot has to be reformulated to match this year’s strain. Last year the vaccine produced
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didn’t exactly match the antigens of the major strains; hence many people who got the shot still got the
flu.
HIV suppresses the immune response by targeting T-helper cells, severely impairing infection defense.
Neisseria gonorrhea and neisseria meningitidis bind and cleave IgA via Ig proteases, helping them to
invade the body.
Slide 14: Every exogenous disease must have a source. Many infectious diseases are not transmissible
(ex: legionella is caught from a water source but is not passed person-to-person).
A review of infection sources along with examples:
Direct spread – mucosa-to-mucosa (ex: gonorrhea or syphilis)
Droplets – cough/sneeze, inhalation (ex: the flu, many respiratory infections)
Water – cryptosporidium is a protozoan parasite that is spread through water causing diarrhea.
Food – listeria; in dairy products/meats, not killed by refrigeration
Soil – blastomyces is a fungal infection (most systemic fungal infections caused by inhalation of spores)
Fomites (inanimate objects that can transmit infections, such as dirty needles) – Hep B, HIV
Vertical transmission (mother transmits infection to the baby) – can be transplacental (in utero during
pregnancy) like cytomegalovirus or syphilis, or perinatal (at time of delivery) like herpes, gonorrhea, or
Chlamydia.
Animal reservoir – rabies virus (saliva of bats, skunks); Lyme disease (has animal reservoir and arthropod
vector)
Arthropod vector – malaria (mosquito, transferred person-to-person by mosquito bites), rocky mountain
spotted fever
Slide 16: Exudative (suppurative) inflammation is pyogenic (forms pus). This can be caused by Grampositive cocci, Gram-negative rods, yeasts, etc. Two terms to know with suppurative infection: abscess –
a collection of pus in a confined space or tissue (ex: top picture of baby’s scalp), and empyema –
collection of pus inside the body cavity (ex: bottom picture of a baby’s brain with meningitis).
Slide 17: Necrotizing inflammation is seen with virulent exotoxins. The lesion could be at a different
location than the site of entry into the body, or the microorganism may not even be present (ex: staph
food poisoning caused by exotoxin, the bacteria never entered the body). Another example is clostridial
myonecrosis or “gas gangrene” (see picture in slide, the dark staining bodies are the organisms, open
circle is the trapped gas).
General Pathology: Pathology of Infectious Diseases, Part I
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Slide 18: Granulomas are the aggregates of mononuclear cells, phagocytes, lymphocytes, giant cells (ex:
TB granuloma) shown in picture. They are usually associated with slow growing intracellular organisms,
most commonly mycobacterium and fungi. Granulomas have noninfectious causes (sarcoidosis, foreign
bodies), so pathologists can culture granulomas or use special staining techniques to tell if it is infectious
or an inactive granuloma from an old insult.
Slide 19: An interstitial (mononuclear) inflammation is characteristic of viruses. Shown is coxsackie
myocarditis. The common progression of this is that a child has a respiratory disease that it never
recovers from and eventually develops heart failure. The bottom x-ray shows a much larger heart
shadow. Coxsackie viruses normally cause colds, but in some people they can invade the heart causing
myocarditis and cardiomyopathy. The heart muscle eventually dies and a heart transplant is required.
The dark staining cells in the slide are lymphocytes and monocytes (chemoattracted there by the
infection).
Remember – think neutrophils for bacteria, and mononuclear WBC’s for viruses. In bacterial pneumonia,
the alveoli were filled with neutrophils; with viral pneumonia the interstitium (not the alveoli) was filled
with mononuclear WBC’s.
In hepatitis viral infection, before the liver is necrotic, the acute inflammatory process is primarily
monocytic.
Slide 20: Cytotoxic/Cytoproliferative inflammation. This is almost always due to obligate intracellular
organisms like viruses. Sometimes you see giant cell formation but mostly viral inclusion bodies. Looking
at viral inclusion bodies can help in diagnosis. Shown in the top picture is a thyroid gland from a child
with a viral infection. You can see the “necklace” of large cells infected with cytomegalovirus (CMV
cells). On the bottom, higher power picture you can see the large cells have cytoplasmic inclusions,
which are viral nucleic acids. This shows the virus is replicating inside the cell. A perinuclear halo can be
seen and this is also indicative of viral prescence in the cell (this is discussed in the viral computer based
lab).