Ch. 13 Flashcards
What is disease?
- a disorder of structure or function leading to signs and symptoms
- a deviation from a normal state of health
What causes disease?
Genetics, environment, and microbes (Koch’s Postulates - microbes cause disease)
Pedigrees
Used to understand what type of Mendelian inheritance pattern diseases or traits follow - human traits.disease follow the principle of inheritance
Cystic Fibrosis (1979-1989)
- CF developed in a person who inherits a mutant form of the gene from both parents
- Clear Mendelian inheritance pattern
- caused by mutated gene, CFTR
- 3 letters out of 3 billion
- took 5 years to narrow it down to 2 million base-pair region
- 10 years and $50 million to find the responsible gene
Discovery of the structure of DNA (1953)
- in 1953, Watson and Crick build a DNA model that fit all the clues that they had gathered from other sources
- 50 years later in 2003 the human genome was sequenced
- Human Genome Project (2003)
Human Microbiome Project
Lack of clarity on human genome and recognition of role of microbes in diseases other than infectious diseases led to this project - referred to as our “second genome”
Barriers
Epithelial surfaces interact with external environments
Normal Micorbes - where they are
- skin and it’s contiguous mucous membranes
- upper respiratory tract (oral cavity, pharynx, nasal mucosa)
- gastrointestinal tract (mouth, colon, rectum, anus)
-outer opening of urethra - Vagina
- external ear and canal
- external eye (lids, lash follicles)
Normal Microbes - where they should not be
All internal tissues and organs
- heart and circulatory system, liver, kidneys and bladder, lungs, brain and spinal cord, muscles, bones, ovaries/testes, glands (pancreas, salivary), sinuses, middle and inner ear, internal eye
Fluids within an organ or tissue
- blood (can contain transient bacteria through brushing your teeth etc), urine in kidneys, ureters, bladder (not completely sterile/ free from micorbes), cerebrospinal fluid, saliva prior to entering the oral cavity, semen prior to entering the urethra
VMS
- Vaginal Microbial Seeding
- take 4x4 gauze inside vagina before c section and taken out after c section and rubbed on baby’s face
How do you know is a baby is breast fed or formula fed?
Bifold-bacteria
- found in breastfed babies
- can synthesize all amino acids and growth factors from simple carbohydrates
- have surface proteins that can bind sugars - fermentation of these sugars provides the infant with calories and lowers gut pH, limiting growth of certain pathogens
HMO
- human milk oligosaccharide
- sugars that are delivered by mother in breast milk - produced to feed bifidobacteria - sugars also go to infant
Normal healthy stool
Bacteroidetes and firmicutes
- balance of micorbes in healthy individual stool varies
- Lee diverse means you have more of a collection of all functions that bacteria play out
Skin
- microbes live only in upper dead layers of epidermis, glands, and follicles ; dermis and layers below are sterile
- dependent on skin lipids for growth
- present in sebaceous glands and hair follicles
Oral cavity - GI Tract
- colonize epidermal layer of cheeks, gingiva, pharynx; surface of teeth; found in saliva in huge numbers; some members involved in dental caries and periodontal diseases
- c. Albicans can cause thrush
- inhabit the gingiva of persons with poor oral hygiene
Large Intestine and Rectum - GI Tract
- areas of lower gastrointestinal tract other than large intestine and rectum have sparse or nonexistent residents
- microbiota consist predominantly of of strict anaerobes; other microbes are aerotolerant or facultative
- yeast can survive this habitat - but not molds
- feed on waste materials in large intestine
Upper Respiratory Tract
Trachea may harbor a sparse population; bronchi, bronchioles, and alveoli are essentially sterile due to local host defenses
Genital Tract
- In females, microbes occupy the external genitalia and vaginal and cervical surfaces; internal reproductive structures normally remain sterile - vaginal colonists respond to hormonal changes during life
- cause of yeast infections
Urinary Tract
- in females, microbiota exist only in the first portion of the urethral mucosa; the remainder of the tract is sterile. In males, the entire reproductive and urinary tract is sterile except for the portion of the anterior urethra
Eyes
The lid am follicles harbor similar microbes as skin; the conjunctiva has a transient population; deep tissues are sterile
Ear
The external ear is similar to the skin in content: areas internal to the tympanum are generally sterile
Skin: common genres
Corynebacterium, propionibacterium, staphylococcus
Oral Cavity: common genres
Streptococcus and Neisseria
Large Intestine and Rectum: common genres
Bacteroides (most abundant in adults), bifidobacterium (most abundant in infants), clostridium, coliforms (escherichia and enterobacter)
Genital Tract: common genres
Lactobacillus and Escherichia
Urinary Tract: common genres
Lactobacillus
Factors that alter normal microbiota
Food, antibiotics, environment, interactions, age, immune status
Dysbiosis
Disruption of microbial population in and on us
- can cause: rheumatoid arthritis, diabetes, Inflammatory bowl disease, obesity, non-alcoholic fatty liver disease, pulmonary disease, asthma, atherosclerosis
Probiotics
Intentional consumption of microorganisms
FMT
- basically an organ transport
- fetal microbiomeal transplantation for people with sever dysbiosis
Resident Microbiota
Normally found in/on our body
Transient Microbiota
Temporary organism (time - some are more like squatters
Pathogen
An organism that is capable of causing disease
- true pathogen
- opportunistic
Virulence
Severity of disease associated with a particular pathogen
Virulence Factor
- component of an organism that supports or enhances its ability to cause disease
Contamination
Contact
- we interact with microorganism
- sometimes contamination can lead to infection if our environment is suitable
Infection
Break barriers, attach, grow, avoid most defenses
- can make it to disease
Disease
Few result in disease
- disrupt normal processes
Direct Expsoure
Physical contact, respiratory contact, vertical (mother to child), biological vectors
Indirect Exposure
Fomites are contaminated through inanimate contact, food, water, droplet nuclei, airborne microbes, aerosols
Respiratory Transmission vs Droplet Nuclei
Difference between distance
- respiratory transmission takes place during normal convo - include coughing and sneezing
- droplet nuclei remain suspended in air and can travel more quickly
Vectors
Mechanical: pathogen outside
- ie housefly, cockroach
Biological: pathogen inside
- ie: mosquito
Parenteral
Bypassing barriers (cuts/needles/fluid-feeding insects)
Placental
Crossing the placental barrier (STORCH OR TORCHES, or SALTORCHES
- syphilis
- toxoplasmosis
- others (Hep B, AIDS, Chlamydia, Listeria, Salmonella)
- Rubella
- cytomegalovirus
- herpes simplex virus
Factors that support infection
- Infectious dose: 50(ID50)
- number of pathogens that will infect 50% of inoculated hosts
- varies with pathogens - Hand washing reduces number of pathogens
- Lethal dose 50(ID50)
- dose that kills 50% of experimental animals within a specified period
Strategies that support attachment of bacteria to cells
Fimbriae, capsule, spikes
Invasion (dissemination) and immune avoidance strategies
Exoenzymes, toxins, blocked phagocytic responses, invasion factors
Exoenzymes
Bacteria produce Extracellular enzymes that dissolve barriers and penetrate through and between cells to invade underlying tissues
Toxins
Toxins (primarily exotoxins) secreted by bacteria cells which die and begin to slough off
Blocked phagocytic response
Bacteria have a property that enables them to escape phagocytosis and continue to grow and cause further infections - ie: capsule
Invasion Factors
Salmonella has a unique system to invade an intestinal cell. After adhering to the cell’s microvilli with its fimbriae, it injects proteins into the cell with a probe-like structure. These proteins disrupt the actin filaments and cause the cell membrane to form a series of ruffles that surround the bacterium and pull it inside. It becomes shielded within a vacuole and begins to grow. From here, it can gain entrance to nearby tissues
Toxins
Endotoxin: lipopolysaccharide (lipid A portion) - gram negative organisms
Exotoxin: any secreted toxin - diverse
Exotoxins
- toxic in small amounts
- impacts the body in a way that is specific to a cell type (blood, liver nerve)
- composed of small proteins
- unstable heat denaturatiom at 60 degrees Celsius
- stimulate the immune system response of antitoxins (an antibody that reacts specifically with a toxin)
- can be converted to a toxoid (an inactivated toxin used in vaccines)
- does not stimulate fever
- secreted from live cell
- a few gram positive and gram negative bacteria
- can cause tetanus, diphtheria, cholera, anthrax
Endotoxin
- toxic in higher quantities
- effects the body systematically and less specific - induces fever, inflammation, weakness, shock
- composed of LPS on cell wall
- stable heat denaturation at 60 degrees Celsius
- can not be converted to a toxoid
- does not stimulate antitoxins
- it is released from cell wall during lysis
- all gram negative bacteria
- can cause meningitis, endoscopic shock, salmonellosis
Exotoxins: A/B toxins
Consist of two portions: A and B
B - binds to target cell and promotes uptake
A - gets translocated into the cytoplasm where it can disrupt cell function/cell signaling
Strategies to avoid immune system
- camouflage - putting things on surface that mimic host cell (putting fake antibodies on surface that look like our own but don’t actually release antibodies)
- Superantigens
- avoidance - getting into an area with poor surveillance
- destroy: A/B toxins destroy immune cells
- confuse
- miscommunication by destroying chmotacix factors that would induce phagocytes
Chain of infection
Agent, virulence, exposure, dose, susceptibility
Stages of Disease
Incubation period, prodromal stage, period of invasion, convalescent period
Incubation Period
Time from initial contact with the infectious agent to the appearance of her symptoms; agent is multiplying. The damage is insufficient to cause symptoms; several hours to several years.
Prodromal stage
Vague feelings of discomfort; nonspecific complaints
- person feels like something is coming on
Period of invasion
Multiplies at high levels, becomes well-established; more specific signs and symptoms
Convalescent Period
As person begins to respond to the infection symptoms decline
Patterns of infection.
- localized (boil)
- systemic (influenza)
- focal infection (infection starts at one location and either pathogen or toxin disseminates throughout the body) - original site remains as home base
- mixed/polymicrobial infection (caused by multiple infectious agents)
- secondary infection (super infections) primary infection results in alteration in environment that leads to the growth of another organisms causing a secondary infection
Sign
Objective evidence of disease as noted by an observer
- Fever, microbes in tissue fluids that should be sterile, abnormal chest, sounds, skin eruptions, leukocytosis, leukopenia, swollen lymph nodes, abscesses, tachycardia, antibodies in serum, septicemia
Symptoms
Chills, pain, irritation, nausea, malaise, fatigue, chest tightness, itching, headache, weakness, abdominal cramps, anorexia, sore throat
Syndrome
Sign + symptom 
Epidemiology
Evidence based science
- science that evaluates occurrence, determinants, distribution, and control of health and sieges in a defined human population
- epidemiologist: one who practice’s epidemiology
- John Snow: was the first epidemiologist- studied cholera in London
- monitor public health: survival and death rates
- respond to disease outbreaks: determine cause and institute control measures
- investigate emerging and re-emerging diseases: determine risk factors and recommend control measures
CDC
- located in Atlanta
- functions as National function for: developing and applying disease, prevention and control, environmental health, and health promotion and education activities
- International counter part is the world health organization located in Geneva, Switzerland
Sporadic disease
Occurs occasionally and at irregular intervals
Endemic disease
Maintains a relatively steady low-level frequency at a moderately regular interval
Hyper-endemic diseases
Gradually increases in frequency above endemic level, but not to epidemic level
Outbreak
- Sudden, unexpected occurrence of disease
- usually focal or in a limited segment of population
Epidemic
- Outbreak affecting many people at once
- sudden increase in occurrence above expected number
- Index case-first case in an epidemic
Pandemic
Increase in disease occurrence within a large population over at least two countries around the world
Morbidity
- an incidence rate
- number of new cases in a specific in a specific time period per unit of population
(number of new cases during a specific period/number of individuals in a population)
Mortality
Number of deaths from a disease per number of cases of the disease
(Number of deaths due to given disease/total number of cases of the disease)
Incidence
Number of new infections over a period of time (typically a year)
Prevalence
number of infected people in a population at a given time
Infectious disease
Disease resulting from an infection by microbial agents
Communicable disease
Can be transmitted from one host to another
Two types of epidemics
- Common source epidemic: single common contaminated source (food)
- Propagated epidemic: one infected individual into a susceptible group, infection propagated to others
Herd immunity
Resistance of a population to infection, and pathogens spread because of immunity of large percentage of the population
- Level can be altered by introduction of new susceptible individuals in a population
- level can be altered by changes in pathogen
A. Antigenic shift: major changes in antigenic character of pathogen.
B. Antigenic drift: accumulation of small, genetic changes over time 
Reproductive number: R0
1/R0 = % of population that is required for R0 to equal 1
Ex: R0 of Covid is 6 - 1/6 = 16% of population needs to be susceptible in order to keep the new cases increasing
Reducing susceptible population
Three types of control
1. Reduce or eliminate source of Reservoir or infection.
2. Break a connection between source and susceptible individual
3. Reduce number of susceptible individuals
- raises herd immunity
- passive immunity following exposure
- active immunity for protection
Systematic Epidemiology
Focuses on ecological and social factors that influence development and spread of emerging and re-emerging diseases
- numerous factors have been identified
Reasons for increase in emerging and re-emerging infectious diseases
World population growth, urbanization, inadequate public infrastructures, increased, international travel, mass, migration, climate, change, habitat disruption, and microbial evolution and development of resistance 
Nosocomial infections
Healthcare acquired infections
- From pathogens within a hospital or other clinical care facility acquired by patience in the facility
- 5 to 10% of all hospital patients acquire a nonsocomial infection
- often caused by bacteria that are members of normal microbiota
- Many hospital strains are antibiotic resistant
- Prolong hospital stays by 4 to 14 days
- result in additional 28 to 33 billion per year to direct healthcare costs
- Result in approximately 99,000 deaths annually
- Proper training of personnel in basic infection control measures - for example, handling of surgical, wounds and handwashing
- monitoring of patient for signs and symptoms of nonscomial infection 
Sources of healthcare associated infections
- Endogenous pathogen
- brought into a hospital by a patient
- Patient is colonized after admission - Exogenous pathogen
- microbiota other than the patients’
- May come from hospital staff, other patients, visitors, food, plants, flowers, keyboards, intravenous and respiratory therapy equipment, water systems like dialysis
