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Pathology, Infection, and Disease
Pathology: the study of disease Etiology: the study of the cause of a disease Pathogenesis: the development of disease Infection: colonization of the body by pathogens Disease: an abnormal state in which the body is not functioning normally
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Normal Microbiota and the Host
Transient microbiota may be present for days, weeks, or months Normal microbiota permanently colonize the host Symbiosis is the relationship between normal microbiota and the host
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Figure 14.1 Representative normal microbiota for different regions of the body.
Bacteria (orange spheres) on the surface of the nasal epithelium Bacteria (brown) on the lining of the stomach Bacteria (orange) in the small intestine
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Symbiosis In commensalism, one organism benefits, and the other is unaffected In mutualism, both organisms benefit In parasitism, one organism benefits at the expense of the other Some normal microbiota are opportunistic pathogens
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Table 14.1 Normal Microbiota on the Human Body
Eyes (conjunctiva) Nose and throat (upper respiratory system) Mouth Skin Large intestine Urinary and reproductive systems (lower urethra in both sexes and vagina in females)
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Normal Microbiota and the Host
Microbial antagonism is a competition between microbes Normal microbiota protect the host by Occupying niches that pathogens might occupy Producing acids Producing bacteriocins Probiotics: live microbes applied to or ingested into the body, intended to exert a beneficial effect
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Koch’s Postulates The same pathogen must be present in every case of the disease. The pathogen must be isolated from the diseased host and grown in pure culture. The pathogen from the pure culture must cause the disease when it is inoculated into a healthy, susceptible laboratory animal. The pathogen must be isolated from the inoculated animal and must be shown to be the original organism.
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Figure 14.3 Koch’s Postulates: Understanding Disease.
Microorganisms are isolated from a diseased or dead animal. The microorganisms are grown in pure culture. 3 The microorganisms are injected into a healthy laboratory animal. 1 2a Colony The microorganisms are identified. 2b 4 Disease is reproduced in a laboratory animal. 5a The microorganisms are isolated from this animal and grown in pure culture. Microorganisms are identified. 5b The microorganism from the diseased host caused the same disease in a laboratory host.
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Koch’s Postulates Koch’s postulates are used to prove the cause of an infectious disease Some pathogens can cause several disease conditions Some pathogens cause disease only in humans
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Classifying Infectious Diseases
Symptom: a change in body function that is felt by a patient as a result of disease Sign: a change in a body that can be measured or observed as a result of disease Syndrome: a specific group of signs and symptoms that accompany a disease
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Classifying Infectious Diseases
Communicable disease: a disease that is spread from one host to another Contagious disease: a disease that is easily spread from one host to another Noncommunicable disease: a disease that is not transmitted from one host to another
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Occurrence of a Disease
Incidence: fraction of a population that contracts a disease during a specific time Prevalence: fraction of a population having a specific disease at a given time Sporadic disease: disease that occurs occasionally in a population
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Occurrence of a Disease
Endemic disease: disease constantly present in a population Epidemic disease: disease acquired by many hosts in a given area in a short time Pandemic disease: worldwide epidemic Herd immunity: immunity in most of a population
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Figure 14.4 Reported AIDS cases in the United States.
120,000 100,000 80,000 60,000 40,000 20,000 Second 250,000 cases Third 250,000 cases Fourth 250,000 Cases First 250,000 cases Expansion of surveillance case definition Number of cases Year
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Severity or Duration of a Disease
Acute disease: symptoms develop rapidly Chronic disease: disease develops slowly Subacute disease: symptoms between acute and chronic Latent disease: disease with a period of no symptoms when the causative agent is inactive
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Extent of Host Involvement
Local infection: pathogens are limited to a small area of the body Systemic infection: an infection throughout the body Focal infection: systemic infection that began as a local infection
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Extent of Host Involvement
Sepsis: toxic inflammatory condition arising from the spread of microbes, especially bacteria or their toxins, from a focus of infection Bacteremia: bacteria in the blood Septicemia: growth of bacteria in the blood
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Extent of Host Involvement
Toxemia: toxins in the blood Viremia: viruses in the blood Primary infection: acute infection that causes the initial illness Secondary infection: opportunistic infection after a primary (predisposing) infection Subclinical disease: no noticeable signs or symptoms (inapparent infection)
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Predisposing Factors Make the body more susceptible to disease
Short urethra in females Inherited traits, such as the sickle cell gene Climate and weather Fatigue Age Lifestyle Chemotherapy
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Incubation period (no signs or symptoms)
Figure 14.5 The stages of a disease. Period of illness Period of decline Incubation period (no signs or symptoms) Prodromal period (mild signs or symptoms) Number of microbes Period of convalescence Most severe signs and symptoms Signs and symptoms Time
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Reservoirs of Infection
Continual sources of infection Human: AIDS, gonorrhea Carriers may have inapparent infections or latent diseases Animal: rabies, Lyme disease Some zoonoses may be transmitted to humans Nonliving: botulism, tetanus Soil
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Transmission of Disease
Contact Direct: requires close association between infected and susceptible host Indirect: spread by fomites Droplet: transmission via airborne droplets
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Figure 14.6ad Contact transmission.
Direct contact transmission Droplet transmission
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Vehicle Transmission Transmission by an inanimate reservoir (food, water, air)
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Figure 14.7 Vehicle transmission.
Water Food Air
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Vectors Arthropods, especially fleas, ticks, and mosquitoes
Transmit disease by two general methods: Mechanical transmission: arthropod carries pathogen on feet Biological transmission: pathogen reproduces in vector
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Figure 14.8 Mechanical transmission.
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Figure Mosquito.
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Nosocomial Infections
Are acquired as a result of a hospital stay Affect 5–15% of all hospital patients
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Figure 14.6b Contact transmission.
Preventing direct contact transmission through the use of gloves, masks, and face shields
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Microorganisms in hospital environment
Figure 14.9 Nosocomial infections. Microorganisms in hospital environment Compromised host Nosocomial infection Chain of transmission
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Common Causes of Nosocomial Infections
Percentage of Total Infections Percentage Resistant to Antibiotics Coagulase-negative staphylococci 15% 89% S. aureus 80% Enterococcus 10% 4–71% Gram-negative rods 15–25% 3–32% C. difficile 13% Not reported
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MRSA USA100: 92% of health care strains
USA300: 89% of community-acquired strains
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Emerging Infectious Diseases
Diseases that are new, increasing in incidence, or showing a potential to increase in the near future
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Emerging Infectious Diseases
Contributing factors Genetic recombination E. coli O157, avian influenza (H5N1) Evolution of new strains V. cholerae O139 Inappropriate use of antibiotics and pesticides Antibiotic-resistant strains Changes in weather patterns Hantavirus
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Emerging Infectious Diseases
Modern transportation West Nile virus Ecological disaster, war, and expanding human settlement Coccidioidomycosis Animal control measures Lyme disease Public health failure Diphtheria
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Clinical Focus 13.1 Influenza: Crossing the Species Barrier
Avian gene pool 1918 H1N1 Human H3N2 North American swine Triple reassortment H1N2 Eurasian swine H1N1 2009 H1N1 pandemic
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Epidemiology The study of where and when diseases occur
Centers for Disease Control and Prevention (CDC) Collects and analyzes epidemiological information in the United States Publishes Morbidity and Mortality Weekly Report (MMWR)
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Epidemiology John Snow 1848–1849
Mapped the occurrence of cholera in London Ignaz Semmelweis 1846–1848 Showed that handwashing decreased the incidence of puerperal fever Florence Nightingale 1858 Showed that improved sanitation decreased the incidence of epidemic typhus
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Epidemiology Descriptive: collection and analysis of data
Snow Analytical: comparison of a diseased group and a healthy group Nightingale Experimental: controlled experiments Semmelweis
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Epidemiology Case reporting: health care workers report specified disease to local, state, and national offices Nationally notifiable diseases: physicians are required to report occurrence
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The CDC Morbidity: incidence of a specific notifiable disease
Mortality: deaths from notifiable diseases Morbidity rate: number of people affected in relation to the total population in a given time period Mortality rate: number of deaths from a disease in relation to the population in a given time
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Number of reported cases
Figure a & b Epidemiological graphs. 40,000 35,000 30,000 25,000 Number of reported cases 20,000 15,000 10,000 5,000 (a) Lyme disease cases, 1999–2010 600 500 400 300 Reported cases per 100,000 people 200 100 Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Month (b) Lyme disease by month, 2009
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Reported tuberculosis cases, 1948–2010
Figure 14.10c Epidemiological graphs. 120 100 80 60 40 20 Reported cases per 100,000 people Year Reported tuberculosis cases, 1948–2010
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Mechanisms of Pathogenicity
Pathogenicity: the ability to cause disease Virulence: the extent of pathogenicity
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Portals of Entry Mucous membranes Skin Parenteral route
Preferred portal of entry
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Numbers of Invading Microbes
ID50: infectious dose for 50% of the test population LD50: lethal dose (of a toxin) for 50% of the test population
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Bacillus anthracis Portal of Entry ID50 Skin 10–50 endospores
Inhalation 10,000–20,000 endospores Ingestion 250,000–1,000,000 endospores
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Toxins Portal of Entry ID50 Botulinum 0.03 ng/kg Shiga toxin 250 ng/kg
Staphylococcal enterotoxin 1350 ng/kg
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Adherence Adhesins/ligands bind to receptors on host cells
Glycocalyx: Streptococcus mutans Fimbriae: Escherichia coli M protein: Streptococcus pyogenes Form biofilms
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Figure 15.1a Adherence. Adhesin (ligand) Pathogen Host cell surface
Receptor Surface molecules on a pathogen, called adhesins or ligands, bind specifically to complementary surface receptors on cells of certain host tissues.
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Figure 15.1b-c Adherence. E. coli bacteria (yellow-green) on human urinary bladder cells Bacteria (purple) adhering to human skin
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Capsules Prevent phagocytosis Streptococcus pneumoniae
Haemophilus influenzae Bacillus anthracis
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Cell Wall Components M protein resists phagocytosis
Streptococcus pyogenes Opa protein inhibits T helper cells Neisseria gonorrhoeae Mycolic acid (waxy lipid) resists digestion Mycobacterium tuberculosis
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Enzymes Coagulase: coagulates fibrinogen Kinases: digest fibrin clots
Hyaluronidase: hydrolyzes hyaluronic acid Collagenase: hydrolyzes collagen IgA proteases: destroy IgA antibodies
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Penetration into the Host Cell Cytoskeleton
Invasins Salmonella alters host actin to enter a host cell Use actin to move from one cell to the next Listeria
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Figure 21.12 Cold sores, or fever blisters, caused by herpes simplex virus.
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Direct Damage Disrupt host cell function Produce waste products Toxins
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The Production of Toxins
Toxin: substance that contributes to pathogenicity Toxigenicity: ability to produce a toxin Toxemia: presence of toxin in the host’s blood Toxoid: inactivated toxin used in a vaccine Antitoxin: antibodies against a specific toxin
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Figure 15.4 Mechanisms of Exotoxins and Endotoxins.
Exotoxins are proteins produced inside pathogenic bacteria, most commonly gram-positive bacteria, as part of their growth and metabolism. The exotoxins are then secreted into the surrounding medium during log phase. Endotoxins are the lipid portions of lipopolysaccharides (LPS) that are part of the outer membrane of the cell wall of gram-negative bacteria (lipid A; see Figure 4.13c). The endotoxins are liberated when the bacteria die and the cell wall breaks apart. Cell wall Exotoxin: toxic substances released outside the cell Salmonella typhimurium, an example of a gram-negative bacterium that produces endotoxins Clostridium botulinum, an example of a gram-positive bacterium that produces exotoxins Endotoxins: toxins composed of lipids that are part of the cell membrane
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Exotoxins Specific for a structure or function in host cell
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Figure 15.5 The action of an A-B exotoxin.
DNA Exotoxin mRNA 1 Bacterium produces and releases exotoxin. A (active) A Exotoxin polypeptides B (binding) B Bacterium A B Receptor Plasma membrane 2 B (binding) component of exotoxin attaches to host cell receptor. Nucleus Cytoplasm Host cell 3 A-B exotoxin enters host cell by receptor-mediated endocytosis. A B 4 A-B exotoxin enclosed in pinched-off portion of plasma membrane during pinocytosis. A B B 5 A-B components of exotoxin separate. The A component alters cell function by inhibiting protein synthesis. The B component is released from the host cell. A B B A Protein
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Membrane-Disrupting Toxins
Lyse host’s cells by Making protein channels in the plasma membrane Leukocidins Hemolysins Streptolysins Disrupting phospholipid bilayer
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Superantigens Cause an intense immune response due to release of cytokines from host cells Symptoms: fever, nausea, vomiting, diarrhea, shock, and death
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By-products of growing cell
Exotoxin Source Mostly gram-positive Relation to microbe By-products of growing cell Chemistry Protein Fever? No Neutralized by antitoxin? Yes LD50 Small
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Exotoxins and Lysogenic Conversion
Lysogeny Corynebacterium diphtheriae A-B toxin + Streptococcus pyogenes Membrane-disrupting erythrogenic toxin Clostridium botulinum A-B toxin; neurotoxin C. tetani Vibrio cholerae A-B toxin; enterotoxin Staphylococcus aureus Superantigen
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Endotoxins Source Gram-negative Relation to Microbe Outer membrane
Chemistry Lipid A Fever? Yes Neutralized by Antitoxin? No LD50 Relatively large
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Figure 15.6 Endotoxins and the pyrogenic response.
Macrophage Endotoxin Hypothalamus of brain Nucleus Cytokines Prostaglandin Fever Blood vessel Pituitary gland Vacuole Bacterium 1 A macrophage ingests a gram-negative bacterium. 2 The bacterium is degraded in a vacuole, releasing endotoxins that induce the macrophage to produce cytokines IL-1 and TNF-. 3 The cytokines are released into the bloodstream by the macrophages, through which they travel to the hypothalamus of the brain. 4 The cytokines induce the hypothalamus to produce prostaglandins, which reset the body’s “thermostat” to a higher temperature, producing fever.
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Portals of Exit Respiratory tract Gastrointestinal tract
Coughing and sneezing Gastrointestinal tract Feces and saliva Genitourinary tract Urine and vaginal secretions Skin Blood Arthropods that bite; needles or syringes
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Figure 15.9 Microbial Mechanisms of Pathogenicity.
When the balance between host and microbe is tipped in favor of the microbe, an infection or disease results. Learning these mechanisms of microbial pathogenicity is fundamental to understanding how pathogens are able to overcome the host’s defenses. H1N1 flu virus penetration or evasion of host defenses damage to host cells Number of invading microbes portals of entry portals of exit Mucous membranes Capsules Cell wall components Enzymes Antigenic variation Invasins Intracellular growth Siderophores Direct damage Toxins Generally the same as the portals of entry for a given microbe: • Respiratory tract • Gastrointestinal tract • Genitourinary tract • Conjunctiva • Exotoxins • Endotoxins • Mucous membranes • Skin • Parenteral route Skin Parenteral route Lysogenic conversion Cytopathic effects Adherence Mycobacterium intracellulare Clostridium tetani Micrographs are not shown to scale.
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