PDF Lecture Notes - Exam 4 FA2024

Chapter 14 - Pathology, Infection and Disease Pathology, Infection and Disease There is a delicate balance between our body’s defense mechanisms and the pathogenic mechanisms of microorganisms. To this point we’ve focused on microbial......

Chapter 14 - Pathology, Infection and Disease Pathology, Infection and Disease There is a delicate balance between our body’s defense mechanisms and the pathogenic mechanisms of microorganisms. To this point we’ve focused on microbial... Structure Function Growth and Control Metabolism Diversity Now we will consider how humans and microorganisms interact in terms of health and disease First, some terminology and background: Pathogen – a disease-causing microorganism Pathology – the scientific study of disease (pathos = suffering; logos = science, study of) Pathology is first concerned with the cause of a disease; its etiology Second, it deals with pathogenesis – the manner in which a disease develops Third, pathology is the study of the structural and functional changes in the body brought about by disease Difference between Infection and Disease: Infection – the invasion and colonization of the body by pathogenic microorganisms Disease – condition in which the infection results in any change from “a state of health” Disease is an abnormal state in which part or all of the body is incapable of performing its natural function An infection may exist in the absence of detectable disease Example: An infection with the pathogenic virus that causes AIDS may exist without causing symptoms of disease The presence of a microorganism in a part of the body where it is not normally found is also an infection Example: E. coli in the urinary tract Pathology, Infection and Disease Normal Microbiota To understand microbial disease – a knowledge of the relationship between microbes and the heathy body is necessary At the beginning of life… 1  A newborn’s first encounter with microbes: Lactobacillus sp. in the birth canal Becomes the predominant intestinal microbe After birth, more microbes are introduced from the food and the environment E. coli begin to inhabit the large intestine Additional microbes establish themselves in and on the body Typical human body may harbor 39 trillion bacterial cells... 9 trillion more than the 30 trillion body cells we have “Microbes that colonize the human body but do not cause disease under normal conditions” – normal microbiota Factors affecting the makeup of microbiota: Available nutrients, pH temperature, [O2], [NaCl] Host defenses, age, nutritional status, health, stress, personal hygiene... others Once established, normal microbiota can benefit the host by preventing overgrowth of harmful microbes - competitive exclusion Example of competitive exclusion: Normal microbiota inhibit the growth of Clostridium difficile Antibiotics can eliminate normal microbiota C. difficile can then grow to levels which cause disease Opportunistic pathogens: “Those microorganisms which ordinarily do not cause disease but can become pathogenic under certain circumstances” Examples: A microbe gains access to a part of the body it is not normally found (E. coli in the urinary tract) Host defense mechanisms are weakened (Pneumocystis pneumonia in AIDS pts.) Normal microbiota is altered, eliminated The Etiology of Infectious Diseases Infectious diseases are those diseases caused by microorganisms Robert Koch, late 19th century, provided the framework for the study of the etiology of infectious disease Recall 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 must cause the disease when inoculated into a healthy, susceptible animal The pathogen must then be isolated from the inoculated animal and shown to be the original organism 2 Classifying Infectious Diseases Every disease alters body structures and functions as indicated by evidence: Symptoms – subjective changes in body function as felt by the patient pain, malaise, nausea, headache Signs – objective changes in body function that can be observed and measured presence of lesions, swelling, fever, paralysis Classifying Infectious Diseases Diseases are often classified based on how they behave within a given population: Communicable disease – any disease that spreads from one host to another, Contagious disease – a disease that is easily spread from one person to another Measles, chickenpox, influenza Noncommunicable disease – not spread from one host to another Example: tetanus Only occurs when Clostridium tetani is introduced into the body via a wound Occurrence of a Disease The full scope of a disease can only be understood if we know something about its occurrence Incidence of a disease – the number of people in a population who develop the disease during a particular time period; the rate of new cases Example: The incidence of AIDS in 2007 was 56,300 – the number of new cases developed in that year Prevalence of a disease is the actual number of cases alive with the disease during a specified period of time; accounts for old and new cases Example: The prevalence of AIDS in 2007 was about 1,185,000 - old and new cases Frequency of occurrence is another criterion for disease classification: Sporadic diseases occur only occasionally typhoid fever in the U.S. Endemic diseases are constantly present in a population common cold Epidemic diseases occur in many people in a given area in a relatively short period of time influenza A pandemic disease is an epidemic disease that occurs world-wide AIDS, influenza influenza 3 Severity or Duration of a Disease Infections can be classified according to the severity or duration of the illness: Acute disease – rapid onset; short course rhinovirus and the common cold Chronic disease – slower development; continues or recurs for a long period of time mononucleosis, tuberculosis, hepatitis B Latent disease – c.a. remains inactive for a time, then activates to produce the disease Varicella virus and shingles Extent of Host Involvement Infections can be classified according to the extent to which a host’s body is affected: Local Infection – invading microbes are limited to a small area boils, abscesses Systemic infection – microbes (or products) are spread throughout the body by blood or lymph measles Focal Infection – is confined to a specific area of the body infections of the teeth, tonsils, sinuses Sepsis – a toxic, inflammatory condition arising from the spread of microbes and their toxins Septicemia – systemic infection arising from multiplication of pathogens in the blood “blood poisoning” Bacteremia – the presence of bacteria in the blood Toxemia– toxins in the blood Viremia – viruses in the blood Patterns of Disease - “A defined sequence of events occurs during infection and disease” Predisposing Factors – conditions that make the body more susceptible to disease and may alter the course of the disease Gender Females – higher rate of UTI’s Males – higher rate of pneumonia and meningitis Genetic background Sickle cell disease – genes inherited from both parents 4  Other predisposing factors include: Inadequate nutrition Age Lifestyle Preexisting Illness Immunodeficiency Patterns of Disease Development of Disease: Once a microorganism overcomes the host defenses – development of disease follows a specific sequence Sequence tends to be the same for acute and chronic diseases 1. Incubation Period – interval between infection and the first appearance of symptoms or signs Length of time depends on: Microorganism Its virulence Number of infecting organisms Resistance of host 2. Prodromal Period – (some diseases): early, mild symptoms such as general aches/malaise 3. Period of Illness – time period when disease is most severe Overt signs and symptoms Fever, chill, aches, pharyngitis, GI, lymph node WBC’s may increase or decrease Period when pt. immune system overcomes the disease; or death occurs 4. Period of Decline – period when signs and symptoms subside 24 hrs. to several days Pt. vulnerable to secondary infections Caused by opportunistic pathogens when body’s defense mechanisms are weakened 5. Period of Convalescence – “recovery”; body returns to its pre-diseased state 5 Spread of Infection Sources of pathogens How diseases are transmitted Reservoirs of infection A continual source of pathogens Required for a disease to perpetuate itself May be living or nonliving Human reservoirs Principal reservoir of human disease is the human body Pathogens transmitted either directly or indirectly Carriers – people who harbor pathogens and transmit them to others without showing any signs of the illness Carriers – play a role in the spread of: AIDS Diphtheria Typhoid fever Hepatitis Gonorrhea Animal Reservoirs Wild and domestic animals – reservoirs for human diseases Zoonosis – disease occurring primarily in animals that can be transmitted to humans Rabies (dogs, skunks, bats, etc.) Lyme disease (field mice) Nonliving Reservoirs Two major reservoirs – water and soil Soil fungi (e.g. ringworm) Clostridium – tetanus, botulism Water – contaminated with human feces Vibrio cholera; Salmonella typhi Also…improperly prepared or stored foods Trichinellosis – Trichinella sipralis Salmonellosis – Salmonella sp. Other food-borne illnesses Staphylococcus sp. Bacillus cereus 6  Transmission of Disease Causative agents of disease can be transmitted from the reservoir of infection to a susceptible host by three principal routes: Contact Vehicles Vectors 1. Contact Transmission – the spread of an agent of disease by: Direct contact Indirect contact Droplet transmission a. Direct contact transmission: person-to-person Direct contact between source and susceptible host; no intermediate involved Direct contact transmission examples: Viral respiratory diseases: cold, influenza Staphylococcal infections Hepatitis A Measles Sexually-transmitted diseases, such as syphilis, gonorrhea, genital herpes Direct, physical contact required Healthcare workers guard against this by using personal protective equipment (PPE) – gloves, gowns, masks, face shields b. Indirect contact transmission Disease is transmitted from its reservoir to a susceptible host by means of a nonliving object (fomite) Examples of fomites - Tissues, towels, bedding, drinking cups Contaminated syringes are fomites for: AIDS Hepatitis B c. Droplet Transmission – droplet nuclei (mucus droplets) that travel a short distance Sneezing, coughing, laughing, talking One sneeze - 20,000 droplets Influenza, pneumonia, pertussis 7  2. Vehicle Transmission – transmission of disease agents by a medium: water, food, air, blood, drugs, IV fluids Waterborne transmission Cholera, shigellosis Airborne transmission Tuberculosis Staphylococcus, Streptococcus, fungi - dust 3. Vectors – Animals that carry pathogens from one host to another Arthropods are the most important group Mechanical transmission - passive transport of pathogens on body parts Biological transmission – biting, defecation, vomiting on host Chapter 15 – Microbial Mechanisms of Pathogenicity Microorganisms possess specific properties that contribute to their: pathogenicity – their ability to cause disease by overcoming the host’s defenses…and virulence – the degree/extent of pathogenicity How Microorganisms Enter a Host To cause disease, most pathogens must: Gain access to host Adhere to host tissues Negate or evade host defenses Damage host tissue Pathogens gain entry to the human host through “avenues” called portals of entry Portals of Entry Mucous membranes – bacteria and viruses gain entry to the body through the mucous membranes lining: Respiratory tract Gastrointestinal tract Genitourinary tract Conjunctiva Most pathogens enter through GI and respiratory tracts 8  Respiratory tract is easiest portal of entry - microbes are inhaled in moisture, dust Common cold Tuberculosis Influenza Gastrointestinal (GI) tract Food, water, contaminated fingers Have to survive stomach acid, bile Cholera Dysentery Typhoid fever Genitourinary tract STIs – sexually-transmitted infections Broken or unbroken mucous membrane HIV Syphilis Gonorrhea Herpes Skin Largest organ in the body Unbroken skin impenetrable to most microbes Hair follicles, sweat glands ducts – entry Broken skin, burned skin – allow pathogen entry to the body Parenteral route Microorganisms deposited directly into tissues under the skin Punctures, injections, bites, wounds, surgery HIV Hepatitis viruses Clostridium tetani - tetanus Clostridium perfringens – gas gangrene Preferred portals Organisms usually produce disease only when gaining entry to the body through a particular “preferred” portal Salmonella typhi Swallowed – typhoid fever Skin entry– irritation only Streptococci Swallowed – no signs or symptoms Inhaled – pneumonia 9  Numbers of Invading Microbes Microbes that gain entry in large numbers are more likely to overcome host defenses Virulence of a pathogen can be expressed as: ID50 – dose at which 50% of a population tested would get the disease... the Infectious Dose ID50 for Bacillus anthracis Cutaneous: 10-50 endospores Inhalation: 10,000-20,000 endospores Ingestion: 250,000-1 million endospores Adherence Most pathogens must attach to host tissues near their portal of entry Ligands on the surface of the pathogen Receptors on the surface of the host cell How Bacterial Pathogens Penetrate Host Defenses Factors that contribute to the ability of bacteria to invade a host: 1. Capsules Formed from glycocalyx Adheres to the outer surface of bacterial cell Impairs phagocytosis Streptococcus pneumoniae with a capsule is virulent 2. Cell Wall Components Streptococcus pyogenes – M Protein Found in cell wall, fimbriae Attachment of bacterial cell to epithelial cells Mycobacterium sp. Waxy cell wall (mycolic acid) resists phagocytosis 3. Enzymes Extracellular enzymes (exoenzymes) produced by some bacteria: Digest material that holds cells together Form or digest blood clots Examples: Coagulases – coagulate fibrinogen in blood to form a clot phagocytosis, walling off of pathogen Kinases – digest clots formed by the host to isolate the pathogen: streptokinase Hyaluronidase – digests hyaluronic acid, a polysaccharide that holds cells together; spreading of infection 10 4. Antigenic Variation Bacterial pathogens can sometimes alter their surface proteins during infection process Body mounts immune response against initial proteins…ineffective against altered protein molecules 5. Penetration into Host Cell Cytoskeleton Actin – a major protein of the cytoskeleton Some pathogens use host cell’s actin to penetrate the cell Salmonella strains and E. coli : Contact host cell plasma membrane Produce proteins that rearrange nearby actin filaments to allow cell entry How bacteria damage host tissues: The Production of Toxins Gram-positive and Gram-negative Among the most lethal substances known - 1 mg botulinum toxin can kill 1 million guinea pigs Two types: exotoxins, endotoxins Exotoxins Produced inside some bacteria Excreted into the surrounding medium Or released upon cell lysis Many are enzymes; can catalyze unwanted reactions Naming exotoxins Host cell attacked Neurotoxins – nerve cells Cardiotoxins – heart cells Enterotoxins – lining of GI tract Associate diseases Diphtheria toxin Tetanus toxin Endotoxins Endotoxins differ from exotoxins – Endotoxins are part of the outer layer of the cell wall Lipopolysaccharide (LPS) layer – endotoxin is lipid: Lipid A Gram-negative bacteria only Lipids instead of proteins Endotoxins are released upon cell lysis 11  Endotoxins stimulate production of cytokines Cytokines are small proteins released by human cells (macrophages) that stimulate the immune response They can produce fever, chills, weakness, aches…even shock and death Shock – a life-threatening condition in which the body and its organs are not getting enough blood flow to function properly low blood pressure; rapid, but ineffective heartbeat Septic Shock - serious condition that occurs when a body-wide infection leads to dangerously low blood pressure Can be caused by many bacteria Gram-negative bacteria: endotoxic shock Endotoxins can activate blood-clotting proteins These proteins induce the formation of small blood clots that obstruct capillaries Clots cause the death of tissues from decreased blood supply Disseminated Intravascular Coagulation (DIC) Endotoxins Representative endotoxin-producing bacteria: Salmonella typhi – typhoid fever Proteus sp. – UTIs Neisseria meningitidis – bacterial meningitis Pathogenic Properties of Viruses and Fungi Like bacteria, viruses and fungi must: Gain access to the host Evade host defenses Damage host cells/tissue Viruses penetrate and grow inside cells where they evade host defenses A virus infection can cause visible changes in the host cell - cytopathic effects 1. Stop cell mitosis 2. Cause release of lysosomal enzymes 3. Form inclusion bodies within cytoplasm or nucleus Vary in size, shape, location Specific to the viral species Sometimes made from viral “parts” (proteins, nucleic acids) 12  “Owl’s Eyes” Inclusion bodies - Cytomegalovirus 4. Induce cell clumping and “rounding-up” Rounding-up of mouse cells in culture; adenovirus e.g 5. Cause fusion of adjacent cells to form syncytia Light micrograph of syncytium (giant cell) formation; a cytopathic effect of the respiratory syncytial virus (RSV) 6. Cause cell death (cytocidal effect) 7. Change antigens on surface of host cell – becomes a target for the immune response 8. Cancer-causing viruses transform host cells The resulting genetic alteration eliminates contact inhibition – unregulated growth is the result 13  Cytopathic effects are used to diagnose many viral infections Pathogenic Properties of Fungi Fungi can: Produce metabolic products toxic to humans Elicit an allergic response Secrete proteases, enzymes which alter host cell membranes and allow fungal cell attachment Produce a capsule to evade phagocytosis Synthesize fungal toxins Aflatoxin – carcinogenic toxin; Aspergillus flavus Chapter 21 - Microbial Diseases of the Skin and Eyes Structure and Function of Skin Review of skin structure – two principal parts: Epidermis Dermis Mucous membranes Found in linings of body cavities such as GI tract, respiratory tract, and genitourinary tract Consist of sheets of tightly packed epithelial cells Many of these cells secrete mucus Function in trapping of particles, microorganisms Bacterial Diseases of the Skin Two genera are frequent causes of skin-related diseases: Staphylococcus Streptococcus Both genera produce invasive enzymes and damaging toxins Staphylococcal Skin Infections Spherical, Gram-positive bacteria forming grape-like clusters of cells Convenient to divide staphylococci into two groups: Coagulase-positive species produce the enzyme that clots fibrin in blood Coagulase-negative species do not have this enzyme Coagulase-negative species are very common on the skin – Staphylococcus epidermidis Up to 90% of the normal microbiota Pathogenic only when skin barrier is broken 14  Coagulase-positive species include: Staphylococcus aureus The most pathogenic of the staphylococci S. aureus is a permanent resident of nasal passages of 20% of the population – carriers Found in most people occasionally S. aureus produces virulence factors: Coagulase Enterotoxins Proteins to block neutrophils Toxins that kill phagocytic cells Antibiotic resistant strains have emerged; difficult to treat – MRSA (methicillin- resistant Staphylococcus aureus) Nosocomial infections and infections within the community Staphylococcal Skin Infections Impetigo – highly contagious skin infection, esp. among children 2-5 years of age Break in the skin; spread to surrounding areas Some staphylococci produce toxins that cause the skin to peel off in layers – scalded skin syndrome Toxin A – causes localized impetigo called bullous impetigo Toxin B – circulates to distant sites causing scalded skin syndrome Treatment of impetigo includes topical and oral antibiotics Scalded skin syndrome requires IV antibiotics and fluid replacement therapy Toxic Shock Syndrome Potentially life-threatening condition First observed when highly-absorbent tampons introduced; childbirth, nasal surgery TSS Toxin 1 – produced by staphylococci at the site of infection; circulates through the bloodstream – systemic effects Nausea, vomiting, fever, rash, shock, organ failure Streptococcal Skin Infections Gram-positive, spherical bacteria growing in chains Cause a wide-range of disease conditions: Meningitis Otitis media Pneumonia Endocarditis Pharyngitis 15  Streptococci can secrete toxins and enzymes to enhance their virulence Hemolysins – lyse RBCs Alpha-hemolytic – incomplete lysis, greening (methemoglobin) Beta-hemolytic – complete lysis of RBCs Beta-hemolytic streptococci are often associated with human disease Separated into serological groups A-T Group A streptococci: S. pyogenes – the most important beta-hemolytic Streptococcus species Streptococcal Skin Infections M Protein enables bacteria to: Evade phagocytosis Prevent activation of complement Adhere to mucous membranes (colonize) Some strains of Group A strep: Produce a capsule Synthesize streptokinases (dissolve clots) and hyaluronidase Streptococcal skin infections are usually localized and superficial If they infect dermal layer of the skin: Erysipelas – serious disease Red patches of skin Local tissue destruction Sepsis possible Cephalosporin is the antibiotic of choice Particularly invasive strains of Group A streptococci (“flesh-eating bacteria”) About 15,000 cases of necrotizing fasciitis each year worldwide Often starts with minor break in the skin Can establish an infection that destroys tissue as fast as a surgeon can remove it Mortality rates of 40% from systemic toxicity Some strains produce Exotoxin A; a superantigen Causes streptococcal toxic shock syndrome similar to that of Staphylococcus Mortality rate for streptococcal TSS very high: up to 80% Treatment: surgical intervention and broad-spectrum antibiotics 16 Skin Infections by Pseudomonads Genus: Pseudomonas; aerobic, Gram-negative rods Pseudomonas aeruginosa – the “model” of an opportunistic pathogen extremely large enzyme “bank” Pseudomonas dermatitis – self-limiting rash; 2 weeks duration Otitis externa – swimmer’s ear; painful infection of the ear canal P. aeruginosa produces several exotoxins Serious opportunistic infection for CF patients and burn victims Frequent cause of nosocomial infections – indwelling catheters, other medical devices…biofilm Infection characterized by blue-green pus; a result of the pigment pyocyanin Treatment: Antipseudomonal beta-lactam antibiotics Silver sulfadiazine for burn pts. Other Bacterial Skin Infections Acne Most common skin disease in humans Three types of lesions 1. Comedonal (mild) acne Topical agents; azelaic acid (Azelex) 2. Inflammatory (moderate) acne Propionibacterium acnes Benzoyl peroxide; erythromycin 3. Nodular cystic (severe) acne Progression of inflammatory acne Deep nodules/cysts; scarring Isotretinoin (Accutane); teratogenic 17 Exam 4 – Study guide Question 1: ____________ serious condition that occurs when a body-wide infection leads to dangerously low blood pressure Chapter 14 Terminology! Including - Pathogen, pathology, disease, infection, etc. Signs vs symptoms Communicable vs contagious, …many others How diseases are classified: Occurrence (sporadic, endemic, epidemic, etc.) Duration (acute, chronic, latent) Extent the host is affected (local, systemic, focal, etc.) How disease-causing microorganisms are transmitted from reservoir of infection to susceptible host 5 steps in the sequence of disease development Chapter 15 Routes of infection, including portals of entry and preferred portals Pathogenic properties of bacteria that allow them to gain access to the host and penetrate host defenses (list and describe) Cytopathic effects of viruses (list and describe) Exotoxins vs Endotoxins Chapter 21 Structure of skin Bacterial Infections of the skin – be familiar with causative agent; disease signs/symptoms; treatments Impetigo Scalded skin syndrome Toxic shock syndrome Necrotizing fasciitis Acne 18