Pathology of Infection Flashcards

1
Q

Introduction

A

Infectious pathology is the most common form of organic and cellular disease. Fortunately, it is often mild and the ‘pathology’ goes virtually unnoticed. Many forms of infection, however, are associated with significant tissue damage or loss of life and infectious disease is still a leading cause of death worldwide.

There are many infectious microorganisms with a variety of special abilities that enable them to infect, proliferate and move on to the next host. Whether or not you get an infection (i.e. show the signs and symptoms of infectious disease) depends upon a highly complex and regulated process that involves not only factors and features of the invading microorganism (e.g. its virulence or disease-producing potential), but also the integrity of a number of host defence mechanisms.

Both humoral and cell-mediated immune systems battle infectious organisms (e.g. humoral immunity more often with bacterial infections and T cells with viral infections) and occasionally cause tissue toxicity that leads to illness and disease. Since the immune system has a limited repertoire of tools, different origins of infectious pathology show a great deal of similarity and overlap in symptoms and pathology. Specific symptoms depend on the location of the invading organism and its predilection for specific organs or tissues.

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2
Q

Are all interactions with microorganisms bad?

A

Not all interactions between humans and microorganisms are harmful. The internal and external exposed surfaces of the body are normally inhabited by a multitude of bacteria, normal microflora, and the host is not adversely affected.

In fact, in some instances, the interaction is mutually beneficial, with the human host providing nutrition and the microorganism secreting essential metabolic byproducts (e.g. vitamin K in the intestinal tract) or keeping more virulent organisms at bay.

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3
Q

Criteria to determine whether bacteria caused disease

A

The treatment of infectious disease is most effective when there is identification of the pathogenic organism and its site(s) of infection. Clinical signs and symptoms are the first step in identification; for instance, a cough is usually indicative of respiratory infection; vomiting or diarrhea of a gastrointestinal infection.

In 1884 the German physician Robert Koch published a set of criteria to determine whether bacteria caused disease. There are some exceptions and limitations to these ‘postulates’ but in general, they are still useful in establishing the infectious origin of a disease.

Koch’s Postulates state that: The organism :

  1. must be found in lesions of the disease.
  2. must be isolated and cultured in vitro.
  3. must transmit the disease to another animal.
  4. must be recovered from lesions in that animal.

Some infectious agents can be directly observed in microscopic sections (e.g. the inclusion bodies formed by CMV (cytomegalovirus) or herpes virus; clumps of bacteria). Many agents require special stains to be visualized based on particular characteristics in their cell walls (e.g. Gram +ve or Gram -ve, acid-fast or silver stains, specific Ab-labelled immunohistochemical stains). Laboratory studies (e.g. isolation and growth of organisms from sputum, blood, stool or urine samples) and radiographic examination (e.g. chest X-ray) result in identification and determination of drug sensitivity of the offending organism in the majority of cases, but not always. The organism may prove difficult to identify or the site of primary infection remain unknown.

Increasingly DNA sequence analysis and PCR-based methods are used to identify microbes that prove elusive to grow in culture and to characterize specific virulent strains. Many of the genomes of bacteria, viruses, fungi and parasites have been completely sequenced. Surprisingly bacteria exchange hundreds of genes from one to another, particularly those genes involved in virulence.

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4
Q

THE ORGANISMS

A
  1. Prions
  2. Viruses
  3. Bacteria
    a. Bacteriophages, Plasmids and Transposons
    b. Chlamydia, Rickettsia, Mycoplasma
    c. Fungi
    d. Protozoa
    e. Helminths
    f. Ectoparasites
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5
Q

Prions

A

infectious proteins (or proteinacious infectious particles), lack DNA or RNA (e.g. Creutzfeld-Jakob disease (CJD), ‘Mad Cow’ disease (new variant CJD) or bovine spongioform encephalopathy (BSE))

represent an abnormal form of a normal host prion protein (PrP)

modify the host protein to undergo a conformational change conferring resistance to degradation

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6
Q

Viruses

A

obligate intracellular organisms, take over genetic apparatus of host cell for their own replication

the viral genome may be DNA or RNA surrounded by a protein coat (capsid)

illnesses may be acute (colds, influenza), chronic (hepatitis B or C) or latent (herpes zoster)

some viruses have the capacity to transform host cells into neoplastic cells (HPV)

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7
Q

Bacteria

A

have a cell membrane but lack membrane-bound nuclei or organelles; also bound by a cell wall

often classified by shape (round - cocci; rods - bacilli, spirochetes); reaction on Gram staining (gram +ve (have a thick cell wall that retains the stain) or Gram –ve (do not stain); or oxygen requirement for growth (aerobic or anaerobic)

pathogenic strains “in the wild”, but normal flora may infect if defenses are down

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8
Q

Bacteriophages, Plasmids and Transposons

A

are mobile genetic elements that infect bacteria and may impart bacterial virulence factors

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9
Q

Chlamydia, Rickettsia, Mycoplasma

A

atypical or intracellular bacteria, lacking certain features typical of bacteria (e.g. no cell wall)

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10
Q

Fungi

A

have thick cell walls and cell membranes

many are normal flora but are common opportunistic infections (e.g. Candida albicans)

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11
Q

Protozoa

A

single-celled organisms that may have complex life cycles (may cycle in multiple hosts and be transmitted from one host to another), e.g. plasmodium falciparum – malaria – replicate in insect vector before transmission to human host; giardia; toxoplasma

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12
Q

Helminths

A

parasitic worms, find 3 classes o roundworms (nematodes – ascaris, hookworms), flatworms (cestodes - pork, beef or fish tapeworms), flukes (trematodes - schistosomes)

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13
Q

Ectoparasites

A

ticks, fleas, lice - attach to and live on the skin

may cause disease directly or be vectors for other organisms (e.g. a deer tick transmits Lyme disease spirochete.

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14
Q

VIRULENCE

A

Virulence are factors that are characteristic of the organisms that allows it to colonize, proliferate, invade and destroy host tissues.

  1. Colonization
  2. Proliferation
  3. Tissue injury
  4. Dissemination and Transmission
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15
Q

Colonization

A

the organism must be able to colonize the site it was introduced to.

Dependent on:
a) size of inoculum
b) ability to adhere to the tissue - viruses: bind to cell surface receptors - bacteria: express adhesion gene products to enhance binding to cell surfaces.

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16
Q

Proliferation

A

dependent upon moisture, oxygen content, pH, and availability of nutrients

must be able to evade host defenses (eg) difficult to digest B encapsulated viruses and bacteria reproduce quickly and covertly overwhelm immune system

must compete with the normal flora

17
Q

Tissue injury

A

infectious agents can establish an infection and damage tissue via
a) directly cause cell death
b) release of toxins and enzymes
c) induce host cellular responses

  1. Viruses
    - damage host cells by entering the cell and replicating at the hosts expense - viral tropism B specific cells for specific viruses
    - kill the host cell in a number of ways:
    a) inhibit host cell metabolic function
    b) affect integrity of host cells plasma membrane
    c) lyse the cell
    d) host immune response destroys the host cell
    e) induce cell proliferation and transformation
  2. Bacteria
    Release toxins. Two types of toxins
    a) endotoxin: a structural component of the cell wall of gram negative bacteria
    b) exotoxin: a secreted toxin which disrupts cell metabolism or plasma membranes.
18
Q

Dissemination and Transmission

A

occur via:
a) tissues planes of least resistance
b) lymphatics
c) axonal transport
d) the cells the organisms infect get carried to distant sites

the infectious organism must be able to leave the host organism (transmission). This can occur via direct contact, airborne, animal or arthropod vector.

Knowledge of means of transmission is important in understanding how a disease develops and controlling outbreaks or preventing further illness by disrupting routes of transmission or removing sources of infection.

19
Q

Host factors - Prevention is the best medicine

A

As hosts, we put up several forms of defense, the most underused of which is our ability to THINK! Simple things like personal hygiene and good skin care go a long way in maintaining the ‘front line’. Beyond this, we depend upon enzymes, acids, detergents, IgA, coughing, cilia and macrophages.

How could an organism get past all this? Easy.
- carelessness, injuries to skin or mucosa, catheterization
- ciliary dysfunction due to smoking, cystic fibrosis, intubation, etc.
- intercurrent infections
- IV drug use
- Etc.

Once they have been successful in getting past the front line of defense, we then depend on our humoral (antibody, cytokines, chemokines, etc.) and cellular immune systems.
- Cytokines influence our immune system by protecting against certain infections and initiating an inflammatory reaction. Some lead to the activation of inflammatory cells and others regulate their growth and differentiation.
- Antibody production by B-cells and opsonization of microorganisms may lead to a complement-mediated or cell-mediated attack and elimination of the infection.

20
Q

Host defenses include

A

a) epithelial (mucosal) and epidermal (skin) barrier

b) immune system B humoral or cellular

c) exogenous factors including antiviral agents, antibiotics, etc.

Therefore, if we were to interfere with any of these host defenses, infection will occur. For example: If we were to suppress our immune system by medications (eg. Transplant patients) we would be susceptible to infections caused by organisms which would not typically occur in healthy individuals with an intact immune system. We call these OPPORTUNISTIC INFECTIONS. The infectious organisms involved usually are of low virulence and include viruses (CMV, herpes virus), bacteria (pneumococcus), fungal (Candida, Aspergillus), protozoa (toxoplasma, pneumocystis)

Development of resistance to antimicrobial agents by microorganisms is a major problem. The main mechanisms for survival of a threatened microorganism are genetic mutation or acquisition of genes with resistance factors.

21
Q

The 5 major patterns of tissue reaction

A

Despite the vast diversity of microbes in the world, the pattern of tissue response is limited. Therefore many pathogens produce identical tissue reaction patterns. There are five major patterns of tissue reaction:

A) Suppurative (PMN) inflammation
- neutrophils are attracted to a site of infection by chemoattractants released from bacteria. Pus.

B) Mononuclear and granulomatous inflammation
- lymphocytes will respond to viruses, intracellular bacteria or parasites
- granulomatous inflammation B characterized by aggregates of epithelioid histiocytes (altered macrophages). Occur with fungal infections or tuberculosis.

C) Cytopathic-cytoproliferative inflammation
- virus mediated damage to host cells will lead to:
1) viral aggregates (inclusion bodies)
2) cell fusion
3) discohesion B blisters
4) proliferation

D) Necrotizing inflammation

E) Chronic inflammation and scarring.

22
Q

Clinical features of an infection:

A
  • Leukocytosis
  • Erythema, pain, and swelling
  • Fever
  • Hypotension and Shock
23
Q

Barriers to Infection

A

As hosts, we have several forms of defense. Simple things like personal hygiene and good skin care (i.e. hand washing!) go a long way in preventing infection. Beyond this we depend upon:
- anatomic barriers (e.g. skin, filtration system of the upper airways)
- enzymes (e.g. lysozyme), acids (e.g. secreted by stomach), detergents (e.g. bile)
- mucous secretions (they contain IgA)
- the mucociliary blanket of the respiratory system (traps organisms which are expelled by coughing)
- macrophages (e.g. those present in airways ingest inhaled particles)
- “good” bacteria (e.g. the microbial flora normally present in the gastrointestinal tract compete with pathogenic bacteria to keep them from establishing a hold in the host).

The first barriers are skin and mucosal surfaces and their secretions. The outer skin layer is constantly shed and renewed and the low pH of the skin (~5.5) and the presence of fatty acids inhibit microbial growth. Wet skin is more permeable to organisms, and organisms may penetrate the warm, moist skin of the genital tract during intercourse (e.g. HPV - venereal warts). Other microorganisms may penetrate through lesions in the skin following:
- injuries to skin or mucosa (e.g. burns, trauma, catheterization, surgery)
- direct ‘inoculation’ (e.g. bites by fleas, ticks, mosquitoes, lice, rabid animals)
- IV drug use (HIV, Hep B)

24
Q

Urinary tract

A

The urinary tract is normally sterile because it is ‘flushed’ several times a day. Women have a much higher incidence of urinary tract infections (UTIs) because of the shorter distance between the urinary bladder and the bacteria-laden skin (5 cm in women versus 20 cm in men).

25
Q

Respiratory system

A

Thousands of viruses, bacteria and fungi are inhaled daily through the respiratory system. Large organisms are trapped in the mucociliary blanket that lines the nose and upper respiratory tract. Ciliary dysfunction due to smoking, cystic fibrosis, or intubation increases the risk of infection.

26
Q

Ingested pathogens

A

Most gastrointestinal pathogens are ingested in food or water contaminated with fecal matter. Safe food handling practices, hand washing and thorough cooking of food can reduce exposure. Normal defenses against ingested pathogens include:

  • acid gastric juice
  • the viscous mucous layer of the gut
  • lytic pancreatic enzymes and bile detergents
  • secreted IgA antibodies
  • competition with abundant microflora in the gut.
27
Q

Outcome of infection

A

The outcome of infection depends on the ability of a microbe to overcome host barriers and defenses. Once a microorganism invades a tissue, one of four things may happen:
- the organism may die and no disease is produced.
- the host may mount a successful immune reaction which results in no symptoms or mild symptoms of disease and subsequent immunity which will abbreviate further infections.
- the host defenses contain, but do not eliminate, the organism and chronic infection results.
- the host defenses are unsuccessful and severe disease or death results

28
Q

SUMMARY - HOW INFECTIOUS AGENTS CAUSE DISEASE

A

Cellular and organic pathology may be the result of direct or indirect microbial toxicity. Additionally host immune or inflammatory responses may cause tissue damage.
- Direct toxicities include cell damage upon invasion, enzymatic degradation of cellular structures, and viral lysis of cells.
- Indirect mechanisms of toxicity include: release of toxins or enzymes (exotoxins or enterotoxins) with remote effects on cells distant to the site of infection; microbial exotoxins and endotoxins may lead to enzyme-mediated cell damage, cellular dysfunction, vascular damage and ischemic necrosis.

Damage may occur during the course of inflammation and phagocytosis of infected cells (e.g. damage caused by host immune/inflammatory responses - leukocytosis, release of cytokines, scarring). Quite often it is the collective immune response that leads to the bulk of cellular or organ damage associated with a given infection.

As a result of the interplay between substances released by microorganisms and those released by our immune system, signs of infection may be distant, generalized or out of proportion to the site and size of the initial inoculum at the time of clinical presentation. Keep in mind that different organisms may cause the same pathology. This overlap is a result of the non-specificity and redundancy built into the inflammatory and immune responses.

In sepsis or the spread of organisms through the blood stream, a cascade of inflammatory mediators (cytokines, etc.) can have marked effects on the recruitment of other inflammatory cells, circulation, thermoregulation and coagulation creating morbidity and potentially death.