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Transcript
FUN2: 10:00-11:00
Scribe: Caitlin Cox
Friday, November 21, 2008
Proof: Ryan O’Neill
Dr. Waites
Pathology of Infectious Diseases
Page 1 of 5
This lecture follows the Infectious Disease chapter in the Robbins textbook of Pathology.
We will talk about examples of different types of infections and mechanisms of diseases, and give examples that
show these. We will talk about the different pathological lesions and give examples of organisms that cause
those lesions. We will talk about bacterial, viral, fungal, and parasitic diseases.
Look at the interactive labs on the website to see the different types of lesions that can result from these different
types of diseases. We will review these on Monday and Tuesday.
I.
II.
III.
IV.
V.
Learning Objectives [S2]:
a. To review host defense against and pathologic responses to infection.
b. To provide an overview of pathologic mechanisms of infectious diseases using specific microbes as examples.
c. To review the different methods by which infectious diseases can be diagnosed. (Review from microbiology)
Top 10 Causes of Death in USA vs. World [S3]:
a. Infections serve an important role in the causes of death.
b. In the United States, influenza, pneumonia, and sepsis are in the top 10 causes of death.
c. In the world at large, infection plays a greater role in the causes of death:
i. Lower respiratory infections
ii. HIV/AIDS
iii. Perinatal infections
iv. Diarrheal diseases
v. Tuberculosis
Host Resistance to Infection [S4]:
a. Why you get an infection is related to host variables and microbe organism variables.
b. Genetics plays an important role.
i. Immunodeficiency diseases hinder the ability of your innate immune system to fight diseases.
1. For example: congenital agammaglobulinaemia.
ii. Cystic fibrosis is an autosomal recessive disease that causes a defect in the transport of chloride ions
across cell membranes.
1. Get a build-up of secretions throughout body, particularly in the lungs.
2. The secretions get colonized by bacteria like Pseudomonas aeruginosa, resulting in chronic
infection.
c. The anatomy and physiology of our bodies are designed to protect us from infection.
i. The skin is very important. A burn allows microorganisms to enter body that ordinarily would not be able to
do so.
ii. Urine flow out of body keeps bacteria that have gained access to the urinary tract from attaching, invading,
and causing disease. If you have physiological problems that hinder urination, you will be more susceptible
to urinary tract infections.
1. For example, a spinal cord disease where you lose voluntary control of your bladder or diabetes
patient may not always able to empty his/her bladder completely.
iii. Immunocompetence relates to the underlying genetics as well here.
d. Circulatory and Ventilatory status
i. If you put an IV in someone’s arm to give them fluids or medicines, you are also providing a route of
infection from the environment into the bloodstream.
ii. If you put a urinary catheter into the bladder, you are allowing bacteria access to the urinary tract.
iii. If someone has respiratory failure and you put an endotracheal tube into the lung to assist their ventilation,
you are bypassing the muco-ciliary defense mechanism, the IgA, the cough reflex, and everything else that
helps protect us from respiratory infections.
e. Underlying disease is the most important.
i. For example, cancer patients die because the cancer weakens their body, and they get an infection or
another complication.
ii. Many different types of underlying diseases compromise the host’s defense, which is why infection can
take advantage when it would not otherwise be able to do so.
Natural Barriers to Infection [S5]:
a. We have a lot of natural barriers to infection.
b. You need to understand that when these are all working properly, we have a high resistance to infection.
Sources of Systemic Infection [S6]:
a. But if you disrupt the normal defense barriers, you get infection.
i. Burns of skin
ii. Trauma
FUN2: 10:00-11:00
Scribe: Caitlin Cox
Friday, November 21, 2008
Proof: Ryan O’Neill
Dr. Waites
Pathology of Infectious Diseases
Page 2 of 5
iii. Dental work allows infections in the mouth to spread to oral tissue, into the bloodstream, and to other parts
of the body.
b. Any organ system where you do something or something changes that alters the normal protective mechanism,
can lead you to have an infection.
VI. Host-Parasite Relationship [S7]:
a. It is the relationship between the host and the invading microorganism that determines the outcome of an
infection.
b. Some infections are worse than others.
c. Virulence factors are the things an organism does that allow it to produce disease or a pathological lesion.
i. If these factors are strong, then the organism will always cause disease.
1. For example, if you do not have immunity to the measles virus, you will get the measles because it is
a very virulent organism. If it is present, it is always going to cause disease.
d. The other factor that affects whether or not a person who is exposed to a microorganism gets a disease is the
infectivity. Infectivity is the ability of an organism to establish itself in a host.
i. Measles is very easily transmitted.
ii. Small pox can spread by aerosols or direct contact very easily; that is why it is so feared as a bioterrorist
weapon.
e. The overall pathogenicity of a microorganism is how virulent it is, plus how easily it is transmitted.
VII. Infection vs. Colonization [S8]:
a. We live in an environment full of microorganisms. Most of them do not cause trouble.
i. The normal flora of our bodies serves many protective functions.
b. It is important to distinguish between the terms: infection and colonization.
i. Infection is the term to describe when the body has been invaded by a pathogenic organism and there is a
visible reaction to the organism in the tissue (lesion, inflammation).
ii. Colonization means there is a microorganism present but you don’t have evidence of infection as
manifested by the immune system or pathological lesions.
VIII. Exogenous vs. Endogenous Infection [S9]:
a. We distinguish between exogenous and endogenous infections.
b. Exogenous infection is one of a microorganism that we do not already have in our body.
i. Must be acquired from the environment.
ii. Typically, these are the bad ones.
c. Endogenous infection is the activation of bugs that are already in our bodies.
i. These are opportunistic in the sense that they are lower virulence.
ii. They only cause disease when the delicate relationship between host and microbe is disrupted by:
1. Stress
2. Radiation exposure
3. Antibiotics that remove normal flora
4. Steroids
5. Chemotherapy that affect host immune system
6. Trauma - allows microorganisms to get into parts of body they would not ordinarily be able to get into
7. Underlying chronic disease that reduces body’s defense mechanisms
IX. Extracellular Pathogens [S10]:
a. We distinguish microorganisms in terms of where they reside, either outside of the cell (extracellular) or they
have adapted to live and reproduce inside the cells of the body (intracellular).
b. If extracellular pathogens are phagocytosed by host cells, they will be destroyed. Therefore, they must have
strategies to avoid being eaten.
i. Capsules prevent phagocytosis.
1. Example: Cryptococcus neoformans is an encapsulated fungal organism.
a. See the large gelatinous capsule in the picture.
ii. Leukocidins, produced by Staphylococcus aureus, are enzymes that kill white blood cells (WBCs)
iii. Many organisms may have multiple serotypes.
1. Example: Streptococcus pneumonia
2. You have an infection of this organism and you develop opsonic antibodies that would aid in
phagocytosis, but the next time you get an infection if it is with a different serovar, then you don’t
have any primed immune system ready to opsonize and phagocytize it.
3. This is why you have to get a flu shot each year.
X. Facultative Intracellular Pathogens [S11]:
a. Lack capsules and toxins, but have developed mechanisms to survive inside host cells:
i. Inhibits fusion of phagocytic vacuoles with lysosomes (ex: M. tuberculosis)
FUN2: 10:00-11:00
Scribe: Caitlin Cox
Friday, November 21, 2008
Proof: Ryan O’Neill
Dr. Waites
Pathology of Infectious Diseases
Page 3 of 5
ii. Resists lysosomal enzymes (ex: Salmonella).
iii. Adapts to cytoplasmic replication (ex: Listeria)
b. Picture shows Legionellae, one of the causes of pneumonia, inside a culture cell
XI. Obligate Intracellular Pathogens [S12]:
a. Have adapted so much that they must get inside host cell in order to survive and reproduce.
b. Cannot damage host unless they can get inside of a host cell.
c. May replicate in a variety of cells, including endothelial, epithelial, phagocytic, or blood cells.
i. Examples: Chlamydia, Rickettsia, Ehrlichia, and viruses.
XII. Other Examples of How Microbes Evade Host Immune Response [S13]:
a. There are a number of different ways that microbes evade host immune system:
i. Hide from immune system
1. C. difficile is an anaerobic bacteria that causes antibiotic-associated diarrhea. It is concealed from
immune system because it grows and lives in mucous layer overlying colon. Since it is in the
mucous, circulating blood, antibodies, WBCs, and complement that would easily be able to
recognize and attack the organism cannot reach it.
ii. Other organisms have developed ways to evade complement-mediated lysis. (ex: E. coli)
iii. Antigenic shift occurs when the organism mutates and/or rearranges its surface antigens.
1. This is why the Influenza virus causes pandemics and why we have to get a new flu shot each year.
iv. HIV evades immune response by actually attacking the T helper cells of the immune system.
v. Many produce IgA proteases that destroy antibodies. (ex: N. gonorrhoeae)
b. Remember that in order to cause disease, they must avoid being killed by the immune system.
XIII. Transmission and Communicability [S14]:
a. How are diseases transmitted?
i. Direct Spread: Mucosal-membrane to mucosal-membrane direct contact because if it is a very fastidious
microorganism, it cannot survive outside of human body. (Neisseria gonorrhoeae)
ii. Droplets (respiratory aerosols), do not have to touch the person to get it. (Influenza Virus)
iii. Drinking contaminated water (Cryptosporidium parvum is a protozoan that lives in water and causes
diarrhea).
iv. Food born (Listeria monocytogenes can survive refrigerated temperatures in dairy products and processed
meats).
v. Soil (Blastomyces dermatitidis is a yeast in the body, a mold in the environment. It is found in dust and dirt,
and you inhale the spores, which germinate in the lungs. Not generally transmitted from person to person.
vi. Fomites are inanimate objects that can carry disease. (Hepatitis B Virus can live on needles and can be
transmitted between drug users who share the same needle).
vii. Vertical transmission:
1. Transplacental, the virus can cross the placenta and invade fetal tissue to cause congenital infection.
(Cytomegalovirus is the most common cause of infection transmitted from mother to offspring.)
2. Perinatal – if the mother has an active herpetic lesion on genitalia, then the baby can acquire the
Herpes Simplex Virus as it is being delivered.
viii. Animal reservoir (Rabies virus lives in the saliva of animals and is transmitted by the animal reservoir biting
another animal or human).
ix. Arthropod vector (Rocky Mountain spotted fever and Lyme disease are carried by ticks.
1. Malaria (Plasmodium vivax) is carried by mosquitoes.
b. Infectious disease does NOT necessarily mean it is transmitted from person to person.
XIV.
Histopathological Responses to Infection: 5 Types [S15]:
a. By looking at the types of pathological lesions that the infection produces in the host, you can get clues as to
what type of infection it is.
b. Exudative (Suppurative) [S16]:
i. Pyogenic (pus-forming) infections are caused by Gram (+) cocci, Gram (-) rods, and yeast,
ii. Pus is a collection of neutrophils.
iii. The tissue becomes necrotic because the bacteria produce toxins and the neutrophils produce enzymes
that destroy the tissue.
iv. Abscess is pus in confined space or tissue.
v. Empyema is a collection of pus in a body cavity. You can see it in the picture in the cranium of a baby that
had bacterial meningitis.
c. Necrotizing [S17]: Many bacteria that produce virulent exotoxins will produce a necrotizing inflammation where
you primarily see tissue death but not much of an inflammatory response.
i. In this case, it is not the bacteria that are multiplying at the site of the lesion; it is the toxin that has travelled
to this site from another part of the body.
FUN2: 10:00-11:00
Scribe: Caitlin Cox
Friday, November 21, 2008
Proof: Ryan O’Neill
Dr. Waites
Pathology of Infectious Diseases
Page 4 of 5
ii. This case is gas gangrene (Clostridial myonecrosis).
1. Clostridium perfringens produces a lecithinase exotoxin. See the eosinophilic bundles of muscle
tissue are dead because of the exotoxin, you see necrosis instead of inflammation.
d. Granulomatous [S18]: Granulomas are aggregates of mononuclear phagocytes, often including Giant Cells
and white blood cells.
i. Granulomas are lesions of slow growing intracellular pathogens, such as mycobacteria and fungi.
ii. Can see it is a granuloma, but cannot tell if it is mycobacteria or fungus. You would have to culture it or do
acid-fast stain.
e. Interstitial (Mononuclear) Inflammation [S19]:
***Remember that in general, neutrophils are associated with bacterial infections and monocytes are associated
with viruses.
i. Mononuclear inflammation is associated with viruses.
ii. Two conditions often caused by viruses are myocarditis and hepatitis.
iii. Picture is x-ray of child with Coxsackie virus respiratory infection. The top x-ray looks fairly normal, but a
few days later, the bottom x-ray shows the cardiac silhouette has greatly enlarged because the virus has
invaded the heart and damaged the heart tissue. The myocardium has been infiltrated in the interstitium by
mononuclear cells as part of the host’s immune response. If you had someone with viral hepatitis, you
would see an analogous infiltration of mononuclear cells in the liver tissue in response to the hepatic virus.
f. Cytotoxic/Cytoproliferative [S20]
i. Unique to virus.
ii. You can see inclusion bodies that illustrate viral nuclear proteins.
iii. Viruses produce intracellular inclusions in nucleus or cytoplasm of infected cell.
iv. Thyroid tissue of newborn, who was infected with the cytomegalovirus.
1. Notice the enlarged cells with the intracytoplasmic and intranuclear viral inclusion.
XV. Pathogenesis of Pyogenic Bacterial Infections [S21-22]:
a. For bacteria to produce disease, it must invade body, attach somewhere, release toxins which stimulate
inflammation, WBCs come to site of infection which release enzymes, and you get tissue damage and necrosis.
b. Tissue Penetration [S23]:
i. Cellulitis is a diffuse spreading of suppuration by bacteria facilitated by their enzymes and toxins, as
opposed to a collection of pus.
ii. Periorbital cellulitis is something optometrists might see. It indicates bacterial infection of H. influenzae.
c. Tissue Penetration and Toxin Production [S24]: can produce very serious and widespread disease.
i. Necrotizing fasciitis (“flesh-eating bacteria,” S. pyogenes)
ii. See skin has desquamated (peeled) off of leg.
iii. See WBCs and bacteria in tissue of Gram stain.
iv. The bacteria penetrate the tissue, produce enzymes and toxins that break down the tissue allowing them to
spread throughout the fascial plane. Ultimately, get thrombosis infarction of the vessels, gangrene of
extremities, and death. The only option is surgical excision or amputation.
d. Attachment to host cell surface adhesions and receptors [S25]:
i. Mycoplasma pneumoniae has an organelle that allows it to attach to the respiratory epithelium, which
directly damages cilia function, recruits WBCs which causes consolidation and pneumonia. The irritation
and damage cause the dry, hacking cough.
e. Multiplication of Organisms [S26]: Streptococcus pneumoniae causes severe lobar pneumonia because the
organism multiplies in the alveoli.
i. You get increased vascular permeability in the acute inflammatory response. Plasma proteins leak into the
alveoli which cause the pink material in the picture (see all the neutrophils).
ii. The lungs fill up with fluid, you get a consolidation on your chest x-ray, and you have difficulty breathing.
iii. All of this because the bacteria are multiplying and stimulating the inflammatory response.
f. Chronic Infections [S27]: are often those that occur inside cells.
i. The picture shows Chlamydia inside a host cell, see a Chlamydial inclusion.
ii. M. tuberculosis is also considered a chronic infection because it is intracellular.
g. Autoimmune Reactions [S28]:
i. Manifestations of many types of infections may not be due to the organism, but due to the host’s response.
ii. The best example of an autoimmune disease is Rheumatic valvular heart disease following Streptococcus
pyogenes pharyngitis. Remember that the M proteins of the Strep. are immunogenic, we make antibodies
against the M proteins, which cross react with antigens in the heart. So the host’s immune system
damages the heart valves, they become stiff, and you get a stenotic mitral valve. That valve is now at
greater risk for bacterial endocarditis if you get an infection later.
FUN2: 10:00-11:00
Scribe: Caitlin Cox
Friday, November 21, 2008
Proof: Ryan O’Neill
Dr. Waites
Pathology of Infectious Diseases
Page 5 of 5
1. This is why the dentist provides antibiotics before treatment to a patient who has a history of
Rheumatic heart disease, because there is a likelihood of bacterial infection due to the damaged
heart.
XVI.
Exotoxins vs. Endotoxins [S29]:
a. These are some of the most important ways that bacteria produce disease.
b. Exotoxins are proteins secreted by living organisms.
i. Can be produced by both Gram (+) and Gram (-) bacterial cells.
c. Endotoxins are part of the lipopolysaccharide component of the Gram (-) bacterial cell wall that are released
when the Gram (-) cells die
d. Exotoxins have a very specific targeted mechanism and affect a specific type of cell or process within a cell.
e. Endotoxins have a broad, non-specific effect on the body as a whole.
XVII. Exotoxins: Cholera Toxin [S30]:
a. Cholera toxin produced by Gram (-) bacteria found in water.
b. Organism does not actually invade, but remains in bowel lumen producing the phage-coded toxin causes “rice
water” stool by activating cAMP and stimulating the secretion of bicarbonate and chloride into the stool, get
large amounts of copious diarrhea, which causes dehydration.
c. Overall, the diarrhea is caused by the toxin altering the molecular transport across epithelia.
XVIII. Bacterial Endotoxins [S31]:
a. These are potential catalysts of the sepsis cascade of increasing symptomatic severity.
b. Endotoxins reside in the outer membrane of Gram (-) bacterial cell wall.
XIX.
Biological Actions of Endotoxin in Septic Shock [S32]:
a. This slide just shows hemodynamic effects of endotoxin.
b. If you get infection of Gram (-) bacteria in blood, there is a great likelihood that you will die of septic shock.
c. Endotoxin can either: cause endothelial injury, activate macrophages, or activate complement.
d. [end 37:05 min]