Principles of Disease AO rev3 revised for 2024 (1) -Pharmacy PDF

Pharmacy Pathology, Infection, and Disease Normal Microbiota The Etiology of Infectious Diseases Nosocomial (Hospital-Acquired) Infections Pathogenicity, the ability to cause disease by overcoming the defenses of a host Virulence, the degree or extent of pathogenicity. Microbiology II : 1 Dr. Mohamm...

Pharmacy Pathology, Infection, and Disease Normal Microbiota The Etiology of Infectious Diseases Nosocomial (Hospital-Acquired) Infections Pathogenicity, the ability to cause disease by overcoming the defenses of a host Virulence, the degree or extent of pathogenicity. Microbiology II : 1 Dr. Mohammad Al-Najjar and Dr. Amin Omar : Introduction 1. Definitions 2. Interactions between hosts and microorganisms 1. DEFINITIONS ▪ Pathology is the scientific study of disease (pathos = suffering; logos = science) Pathogenesis: the manner in which a disease develops. Pathogenicity, the ability to cause disease by overcoming the defenses of a host Pathogen: A microorganism causes infection/disease Etiology: Cause of disease. Virulence, the degree or extent of pathogenicity Infection/disease: Although the terms are sometimes used interchangeably, they differ somewhat in meaning. ❑ Infection is the invasion or colonization of the body by pathogenic microorganisms; ❑ Disease occurs when an infection results in any change from a state of health to abnormal state ❖ An infection may exist in the absence of detectable disease. For example, AIDS with no symptoms of the disease. ❑ The presence of a particular type of microorganism in a part of the body where it is not normally found is also called an infection—and may lead to disease. Inflammation:- a localized tissue response to injury or infection characterized by redness, swelling, pain in the affected area, warmth, and an accumulation of phagocytic cells (Pus). Factors Determine The Distribution And Composition Of The Normal Microbiota Among these factors: ❖ Nutrients, ❖ Physical and chemical: temperature, pH, available oxygen and carbon dioxide, salinity, and sunlight energy source ❖ Mechanical factors, For example, 1. The chewing actions of the teeth and tongue movements, 2. The flow of saliva and digestive secretions 3. The flushing action of urine 4. Mucus and cilia in the respiratory system, ❖ Defenses of the host, and. Age, nutritional status, diet, health status, disability, hospitalization, emotional state, stress, climate, geography, personal hygiene, living conditions, occupation, and lifestyle. Relationships between the Normal Microbiota and the Host Normal microbiota prevent the overgrowth of harmful microorganisms by microbial antagonism, or competitive exclusion. Microbial antagonism involves competition: – For nutrients, – Producing substances harmful to the invading microbes E. coli cells produce bacteriocins, proteins that inhibit the growth of other bacteria of the same or closely related species, such as pathogenic Salmonella and Shigella., – Affecting conditions such as pH. When pH is altered by antibiotics, Candida albicans overgrow which lead to a form of vaginitis (vaginal infection). Clostridium difficile become a problem when normal microbiota are eliminated by antibiotics ends with severe or even fatal colitis The relationship between the normal microbiota and the host is called symbiosis and takes different forms: 1. Commensalism, one of the organisms benefits, and the other is unaffected. For Examples: ❑ Staphylococcus epidermidis that inhabit the surface of the skin, 2. Mutualism: both organisms get benefits. For example, ❑ E. coli, in large intestine synthesize vitamin K and some B vitamins.. 3. Parasitism. one organism benefits by depriving nutrients at the expense of the other. for Example: ❑ Many disease-causing bacteria are parasites. Opportunistic Microorganisms Opportunistic pathogens: They ordinarily do not cause disease in their normal habitat in a healthy person but may do so in a different environmental conditions such as: – Gains access to other body sites -through broken skin or mucous membranes such a E. coli – Host immunity is weakened or compromised by infection- for example: ❖ AIDS is often accompanied by a common opportunistic infection because they are immunocompromised , such as Pneumocystis pneumonia (fungal). – Cooperation among Microorganisms can be a factor in causing disease. For example, ❖ Pathogens that cause periodontal disease and gingivitis have been found to have receptors, not for the teeth, but for the oral streptococci (Normal Flora) that colonize the teeth. The Etiology of Infectious Diseases Etiology of Infectious disease caused by microbes is determined by microbiologists according to Koch’s postulates summarized as follows: 1. The pathogen must be isolated from the diseased host and grown in pure culture. 2. The pathogen from the pure culture must cause the disease when it is inoculated into a healthy, susceptible laboratory animal. 3. The pathogen must be isolated from the inoculated animal and must be shown to be the original organism. 4. The same pathogen must be present in every case of the disease Exceptions to Koch’s Postulates 1. Some microbes have unique culture requirements, For example: – The bacterium Treponema pallidum is known to cause syphilis, but virulent strains have never been cultured on artificial media. 2. Signs and symptoms of certain diseases exhibited only in human. 3. Some infectious diseases have poorly defined etiologies or no clearcut. For example, ❑Nephritis (inflammation of the kidneys) is caused by several different pathogens, that show the same signs and symptoms. 4. Some pathogens can cause several disease conditions. For example: ❑Mycobacterium tuberculosis, for example, is implicated in diseases of the lungs, skin, bones, and internal organs. ❑ Streptococcus pyogenes can cause sore throat, scarlet fever, skin infections (such as erysipelas), Transmission of microorganisms Most microbes are categorized as communicable (infectious)→ able to be transmitted between hosts, The source of the microbe may be another host or some nonliving disease reservoir→ To be successful pathogen of a communicable disease, a microorganism must be able to : 1. Survive passage from one host to another or from the reservoir to the host. 2. Attach to or penetrate the host’s tissues 3. Withstand (for a period of time) the host’s defense mechanisms. 4. Induce damage to or malfunction of the host’s tissues. 10 Classifying Infectious Diseases Symptoms: changes in body function, such as pain (These subjective changes aren’t apparent to an observer) Signs, - changes can observe and measure by the physicianinclude lesions swelling, fever. Syndrome group of symptoms or signs are evaluated together. Communicable disease : spreads from one host to another, either directly or indirectly… Noncommunicable disease is not spread from one to another Frequency of occurrence can classify diseases as: 1 Sporadic disease; occurs only occasionally, typhoid fever 2 Endemic disease; disease constantly present in a population , common cold. 3 Epidemic disease; many people in a given area acquire a certain disease in a relatively short period, influenza 4 Pandemic disease; epidemic disease that occurs worldwide‫و‬ Covid-19 12 Severity or Duration of a Disease Acute disease is one that develops rapidly but lasts only a short time.. (tonsilitis) Chronic disease develops more slowly, and continue or recur for long periods.. (Lyme disease) Subacute disease; A disease that is intermediate between acute and chronic. Latent disease is one in which the causative agent remains inactive for a time but then becomes active to produce symptoms of the disease. (Versilia zoster viral infection) Herd Immunity: many immune people are present in a community. Extent of Host Involvement Local infection ;invading microorganisms are limited to a relatively small area of the body. Such as boils and abscesses. Systemic (generalized) infection, microorganisms or their products are spread throughout the body by the blood or lymph. Such as Measles and scarlet fever. Focal infection. agents of a local infection enter a blood or lymphatic vessel and spread to other specific parts of the body, Sepsis is a toxic inflammatory condition arising from the spread of microbes, Septicemia, blood poisoning, arising from the multiplication of pathogens in the blood. Septicemia is a common example of sepsis. Bacteremia is the presence of bacteria in the blood Toxemia refers to the presence of toxins in the blood Viremia refers to the presence of viruses in blood. Primary infection is an acute infection that causes the initial illness. Secondary infection caused by an opportunistic pathogen after the primary infection has weakened the body’s defenses. For example; Any viral, fungal or bacterial disease following infected with AIDS streptococcal bronchopneumonia following influenza Subclinical (inapparent) infection is one that does not cause any noticeable illness. Such as Poliovirus, AIDS, H. pylori, hepatitis A virus. Predisposing Factors Predisposing factors make the body more susceptible to a disease and may alter the course of the disease. 1. Gender; example, females have a higher incidence of urinary tract infections than males, whereas males have higher rates of pneumonia and meningitis. 2. Genetic background may play a role as well. For example, sickle cell disease is a severe, Individuals who carry only one sickle cell gene are relatively resistant to the most serious form of malaria. 3. Climate and weather In temperate regions, the incidence of respiratory diseases increases during the winter. 4. Other predisposing factors include inadequate nutrition, fatigue, age, environment, habits, lifestyle, occupation, preexisting illness, chemotherapy, and emotional disturbances. Development of Disease 1. Incubation Period: The incubation period is the interval between the initial infection and the first appearance of any signs or symptoms – Time of incubation depends on the specific microorganism involved: Virulence (degree of pathogenicity), Number of infecting microorganisms, and the Resistance of the host. 2. Prodromal Period is a relatively short period that follows the period of incubation. – characterized by early, mild symptoms of disease, such as general aches and malaise. 3.Period of Illness : During which the disease is most severe. 4. Period of Decline : Signs and symptoms subside. The fever decreases, and the feeling of malaise diminishes. During this phase, the patient is vulnerable to secondary infections. 5. Period of Convalescence: the person regains strength and the body returns to its prediseased state.. ManalAyyash;MSc Transmission of Disease By three principal routes: contact, vehicles, and vectors. 1. Contact transmission is the spread of an agent of disease by direct contact, indirect contact, or droplet transmission. a. Direct contact transmission, also known as person-toperson transmission, such as touching, kissing, and sexual intercourse. b. Indirect contact transmission occurs by means of a nonliving object which is called a fomite. Examples of fomites : tissues, handkerchiefs, towels, bedding, diapers, drinking cups, eating utensils, toys, money, and thermometers.. c. Droplet transmission in which spread in droplet (mucus droplets) that travel only short distances (less than 1 m) in air by coughing, sneezing, laughing, and talking. 2. Vehicle Transmission: by a medium, such as water, food, or air ,blood and other body fluids, drugs, and intravenous fluids. a. Airborne transmission refers to the spread of agents of infection by droplet nuclei in dust that travel more than 1 meter and remain in air for prolonged periods b. Waterborne by water contaminated with Sewage. c. Foodborne transmitted in foods that are incompletely cooked, poorly refrigerated, or prepared under unsanitary conditions. (Both waterborne and foodborne transmission also provide a transfer of microbes by fecal-oral transmission) 3. Vectors: biological agents Arthropods are the most important group of vectors. They transmit disease by two general methods: a. Mechanical transmission: passive transport of the pathogens on the insect’s feet or other body parts. b.Biological transmission: active process and is more complex. The arthropod bites an infected person or animal and ingests some of the infected blood. Healthcare-Associated Infections (HAIs) or Nosocomial (Hospital-Acquired) Infections The word nosocomial is derived from the Greek word for hospital. It is acquired as a result of a hospital stay. Nosocomial infections result from the interaction of several factors: (1) Microorganisms in the hospital environment, (2) The compromised (or weakened) status of the host (3) The chain of transmission in the hospital. Emerging Infectious Diseases Emerging Infectious Diseases (EIDs) are ones that are new or changing, showing an increase in incidence in the recent past, or a potential to increase in the near future. Contributing factors: – Evolution of new strains V. cholerae O139, E. coli O157:H7 – Inappropriate use of antibiotics and pesticides Antibiotic resistant strains – Changes in weather patterns (Global warming) increase the distribution and survival of reservoirs and vectors – Modern transportation systems (airplanes ventilation systems) – Ecological disaster, war, expanding human settlement Coccidioidomycosis (California after 1994 earthquake) – Insect vectors and Animal control measures (Lyme disease due to rise in deer population) – Public Health failure (Diphtheria) - Bioterrorism, the use of pathogens or toxins to produce death and disease in humans, animals, or plants Epidemiology It is the science that studies when and where diseases occur and how they are transmitted in populations. Morbidity: incidence of a specific notifiable disease Mortality: deaths from notifiable diseases Morbidity rate = number of people affected/total population in a given time period Mortality rate - number of deaths from a disease/total population in a given time Mechanisms of Pathogenicity How Microorganisms Enter a Host To cause disease, most pathogens must: ❖ Gain access to the host, ❖ Adhere to host tissues, ❖ Penetrate or evade host defenses, and ❖ Damage the host tissues. Some microbes cause disease by: ❖ Directly damaging host tissue. ❖ Accumulation of microbial waste products. The portals of entry for pathogens are: ❖ Skin ❖Mucous membranes ❖ Parenteral route : direct deposition beneath the skin or membranes. ❖ Preferred route 1. The portals of entry 1. Skin The skin is the largest organ of the body in terms of surface area and weight Important defense against disease. Some microbes gain access to the body through: ❖Openings in the skin, such as hair follicles and sweat gland ducts. ❖Boring through intact skin as Larvae of the hookworm (nematodes) ❖ Grow on the keratin in skin as fungi. ❖Infect the mucous membrane itself such as The conjunctiva (a delicate mucous membrane that lines the eyelids and covers the white of the eyeballs. 2. Mucous Membranes The portals of entry Line the respiratory tract, gastrointestinal tract, genitourinary tract, and conjunctiva (a delicate membrane that covers the eyeballs and lines the eyelids). A. The respiratory tract – The easiest and most frequently traveled portal of entry for infectious microorganisms – Diseases that are commonly contracted via the respiratory tract include > the common cold, pneumonia, tuberculosis, influenza, and measles. B. Gastrointestinal tract Microorganisms – Most microbes are destroyed by hydrochloric acid (HCl) and enzymes in the stomach or by bile and enzymes in the small intestine.. – Microbes in the gastrointestinal tract can cause ❖ Poliomyelitis, hepatitis E & A, typhoid fever, amebic dysentery, giardiasis, shigellosis (bacillary dysentery), listeriosis, salmonellosis and cholera. ❖ These pathogens are then eliminated with feces C. Genitourinary pathogens cause sexually transmitted infections (STIs) ❖ Examples of STIs are HIV infection, genital warts, chlamydia, herpes, syphilis, Borrelia and gonorrhea. The portals of entry 3.The Parenteral Route Tissues beneath the skin or injured mucous membranes is called the parenteral route. ❖Punctures, injections, bites, cuts, wounds, surgery, and splitting of the skin or mucous membrane due to swelling or drying can all establish parenteral routes. ❖HIV, the hepatitis viruses, and bacteria that cause tetanus, Lyme disease and gangrene can be transmitted parenterally 4. The Preferred Portal of Entry – Preferred portal of entry that is a prerequisite to be able to cause disease. ❑ For example, ✓Typhoid fever, Salmonella typhi, preferred route is swallowing. ✓Streptococci cause pneumonia , preferred route by inhaling – Some microorganisms can initiate disease from more than one portal of entry. Such as: ❖ Yersinia pestis and Bacillus anthracis, 2. Numbers of Invading Microbes It is expressed as ID50 (infectious dose for 50% of a sample population). The ID50 is not an absolute value; rather, it is used to compare relative virulence under experimental conditions. ❑For example: ID 50 of Bacillus anthracis depend on portal entry o Through the skin (cutaneous anthrax) is 10 to 50 endospores; o Inhalation 10,000 to 20,000 endospores; o Gastrointestinal 250,000 to 1,000,000 endospores. The potency of a toxin is expressed as the LD50 (lethal dose for 50% of a sample population). ❑ For example, the LD50 for ✓ Botulinum toxin in mice is 0.03 ng/kg; for ✓ Shiga toxin, 250 ng/kg; and ✓ Staphylococcal enterotoxin, 1350 ng/kg. In other words, the lower the LD50 the higher the potency How Bacterial Pathogens Penetrate Host Defenses Several factors that contribute to the ability of bacteria to invade a host include capsule, cell wall component, enzymes, ---------. Details are followed 1. Capsules Glycocalyx material that forms capsules around their cell walls; The capsule resists phagocytosis by the host’s Example: Streptococcus pneumoniae, only capsulated Strains are virulent. Klebsiella pneumoniae, a causative agent of bacterial pneumonia 2. Cell Wall Components Heat-resistant and acid-resistant protein called A. M protein produce by Streptococcus pyogenes found on both the cell surface and fimbriae. B. Fimbrae and Opa protein in Neisseria gonorrhoeae grows inside human epithelial cells and leukocytes. C. The waxy lipid (mycolic acid) that makes up the cell wall of Mycobacterium tuberculosis also increases virulence by resisting digestion by phagocytes, and can even multiply inside phagocytes. 3. Enzymes Production of extracellular enzymes (exoenzymes) and related substances. These chemicals can digest materials between cells and form or digest blood clots, among other functions a.Coagulases are bacterial enzymes that coagulate (clot) the fibrinogen in blood. b. Bacterial kinases are bacterial enzymes that break down fibrin and thus digest clots formed by the body to isolate the infection such as : fibrinolysin (streptokinase) c. Hyaluronidase hydrolyzes hyaluronic acid, a type of polysaccharide that holds together certain cells of the body, particularly cells in connective tissue. 4. Antigenic Variation Some pathogens can alter or activate alternative genes of their surface antigen to escape host immune antibodies. Examples 1. N. gonorrhoeae has several copies of the Opa-encoding gene. 2. Influenza virus 3. Trypanosoma brucei gambiense the causative agent of African trypanosomiasis (sleeping sickness). How Bacterial Pathogens Damage Host Cells When a microorganism initially encounters (avoid) phagocytes of the host and overcomes the host’s defense, then the microorganism can damage host cells in four basic ways: (1) Using the host’s nutrients; Bacteria can obtain Iron by: – Siderophores which are proteins secrete by microbes to obtain free iron from iron transport proteins lactoferrin, transferrin, Hemoglobin and ferritin of the host. (2) Causing direct damage in the immediate vicinity of the invasion; by rupturing the cell during penetration or after multiplication (3) Producing toxins, transported by blood and lymph, (4) Inducing hypersensitivity reactions: immune response Bacterial Toxins Most damage by bacteria, is done by toxins. Toxins are poisonous substances that are produced by certain microorganisms. Toxigenicity. The capacity of microorganisms to produce toxins Toxins can be transported by the blood or lymph can cause serious, and sometimes fatal, effects.. Toxemia refers to the presence of toxins in the blood. Types of toxins are, exotoxins and endotoxins A. Exotoxins: Produced inside some bacteria as part of their growth and metabolism Exotoxins are proteins, and many are enzymes Exotoxins are produced by both gram-positive and gram-negative. Diseases caused by bacteria that produce exotoxins are often caused by small amounts of exotoxins, not by the bacteria themselves. – For example, botulism is usually due to ingestion of the exotoxin, not to a bacterial infection. Toxoids are inactivated toxins by heat or by formaldehyde, iodine, or other chemicals, Cannot cause the disease. Used as vaccine to stimulate the body to produce antitoxins.. Types of exotoxins 1. A-B Toxins : consist of two parts designated as A and B, A part is the active (enzyme) component, and the B part is the binding component (H. pylori). 2. Membrane-Disrupting Toxins cause lysis of host cells by disrupting their plasma membranes (Staph and Streptococcus). 3. Superantigens: are antigens that provoke a very intense immune response (S. aureus) B. Endotoxins A.Endotoxins differ from exotoxins in several ways. 1. They are part of the outer portion of the cell wall of gram-negative bacteria lipopolysaccharides (LPS), LPS is made of 3 portions : lipid A (as endotoxin), core and O polysaccharide B. 2.Endotoxins are released when die or during bacterial multiplication 3.Endotoxins stimulate T-lymphocytes to release cytokines in very high concentrations.. All endotoxins produce the same signs and symptoms, regardless of the species of microorganism, although not to the same degree. These include – Chills, fever, weakness, generalized aches, and, in some cases, shock and even death. Portals of Exit In general, a microbe uses the same portal for entry and exit. Microbes may leave the body via specific routes called portals of exit in secretions, excretions, discharges, or tissue that has been shed. The most common portals of exit are: 1. Respiratory tract exit in discharges from the mouth and nose; such discharges are expelled during coughing or sneezing. – Examples of Pathogens that are discharged through the respiratory route: ❖ cause tuberculosis, whooping cough, pneumonia, scarlet fever, meningococcal meningitis, chickenpox, measles, mumps, smallpox, and influenza 2. Gastrointestinal tract in feces or saliva. Feces may be contaminated with pathogens associated with salmonellosis, cholera, typhoid fever, shigellosis, amebic dysentery, and poliomyelitis, listeriosis. Saliva can also contain pathogens, such as those that cause rabies, mumps, and infectious mononucleosis. 48 3. Genitourinary tract. Microbes responsible for sexually transmitted infections are found in secretions from the penis and vagina. Urine can also contain the pathogens responsible for typhoid fever and brucellosis, which can exit via the urinary tract. 4. Skin or wound infections are other portals of exit. Infections transmitted from the skin include yaws, impetigo, ringworm, herpes simplex, and warts. 5. Infected blood can be removed and re-injected by biting insects and contaminated needles and syringes to spread infection within a population. ❖ Examples of diseases transmitted by biting insects are yellow fever, plague , tularemia , and malaria. ❖ Examples of diseases may be transmitted by contaminated needles and syringes are AIDS and hepatitis B 49