midterm Flashcards
1
Q
inside the cells release residual content
A
autophagosomes
2
Q
different (outside) pinocytosis fused with primary lysosomes
A
heterophagosomes
3
Q
study of “cause” of a disease
A
Etiology
4
Q
deals with “how a disease develops”
A
Pathogenesis
5
Q
cell Adaptions
A
Prolonged exposure of cells to negative or exaggerated normal conditions causes various adaptations to: – Cell, tissues, organs ■ Atrophy ■ Hypertrophy ■ Hyperplasia ■ Metaplasia ■ Intracellular accumulations ■ Aging
6
Q
Intracellular Accumulations
Three types of intracellular accumations
A
- Anthracosis (coal/carbon particles)
- Hemosiderosis
- Lipid accumulation
7
Q
early stages of black lung disease
– Exogenous material accumulation
– Seen in lungs of coal miners and cigarette smokers
A
Anthracosis (coal/carbon particles)
8
Q
Accumulation of blood-derived brown pigment
– Derived from hemolyzed red blood cells
– Eg. Hereditary hemochromatosis – genetic disorder of liver (overabsorption of iron
from food)
A
Hemosiderosis
9
Q
Decrease in size of a cell, tissue, organ or entire body
– Can be a reduced size of a cell, reduced number of cells or both
– Aging and damaged organelles are eaten by autophagosomes and digested
■ Undigested residues form lipid-rich brown pigment called lipofuscin
■ Undigested proteins are taken up by ubiquitin (scavenger protein) and marked for
destruction
A
atropy
10
Q
hypertrohy
A
Hypertrophy – increase size of tissue or organs due to enlargement of individual cells
– “trophe” = food overfed
– Hypertrophy in cardiac muscles of the heart (as in hypertension) and skeletal muscle (as in bodybuilders)
11
Q
increase in size of tissue or organs due to an increased number of cells
– Chronic stimulation – callus (corn) – overgrowth of stratum corneum
– Hormones – uterus (endometrial hyperplasia due to action of estrogen)
– Hyperplasic polyps of intestines; Benign prostatic hyperplasia in elderly men
A
Hyperplasia
12
Q
– Change of one cell type into another
– Eg. Smokers – columnar cells of the bronchial mucosa stratified squamous
epithelium
■ Reversible change
■ If stimulus remains the metaplasia may progress to dysplasia
A
Metaplasia
13
Q
– Disorderly arrangement of cells and nuclear change
– Can progress to neoplasia (Cancer)
A
■ Dysplasia
14
Q
– Fatty livers (steatosis) due to chronic alcohol abuse or diabetes mellitus
A
Lipid Accumulation
15
Q
Cell Death
■ Two Reasons Why Cells Die:
A
1. Irreversible cell injury – Necrosis: localized death of cells or tissues in a living organism ■ Coagulative ■ Liquefactive ■ Caseous ■ Enzymatic fat Necrosis 2. Apoptosis (“dropping out”) – Programmed cell death (single cells)
16
Q
– Most common
– Cause: anoxia
■ Rapid inactivation of hydrolytic enzymes prevents lysis
– Outcome: cell membrane is preserved, organelles and nucleus coagulate
– Solid internal organs: heart, liver, kidneys
A
Coagulative Necrosis
17
Q
– Cause: cell is completely digested by hydrolytic enzymes – Eg. brain infarct
– Outcome: Dissolution of tissues soft and liquify
– Brain, skin, joints
A
■ Liquefactive Necrosis
18
Q
– Cause: Tuberculosis (TB) patients center part of tuberculous granuloma
becomes necrotic and cells fall apart
■ Cheesy
■ Also found with fungal infections (histoplasmosis)
– Lungs
A
Caseous Necrosis (special form of coagulative necrosis)
19
Q
– Caused by lipolytic enzymes and limited to fat tissues usually around the pancreas
– Cause: rupture of pancreas (acute pancreatitis)
■ Enzymes release into adjacent fat tissue degrade fat into glycerol and free fatty acids
■ Forms calcium soaps
A
■ Enzymatic Fat Necrosis (special form of liquefactive necrosis)
20
Q
condensation of chromatin
A
Pyknosis
21
Q
fragmentation of nucleus ‘nuclear dust’
A
Karyorrhexis
22
Q
dissolution of nuclear structure as a result of enzymatic digestion
A
Karyolysis
23
Q
■ Active form of PROGRAMMED cell death by ‘suicide genes’ ■ Affects single cells – Cell divides into apoptotic bodies taken up by macrophages
A
apoptosis ■ Physiologic Apoptosis – – Eg. Fetal development ■ Pathologic Apoptosis – – Eg. Liver cells infected with hepatitis Note: Lack of apoptosis can be seen in disease – Eg. Chronic Lymphocytic Leukemia
24
Q
What are oxygen radicals, and how do they damage cells?
A
Toxic oxygen radicals are formed in small amounts in cells, but they are rapidly catabolized.
Reversible cell injury:
- hydrogen peroxide (H2O2)
- hydroxyl radicals (OH)
cause direct DNA, protein, and membrane damage.
25
How do toxins, microbes, and chemical mediators of inflammation kill cells?
Toxins kill cells through direct and indirect effects on cell structure and function.
Microbes kill cells by mediating direct cell lysis (some viruses) by activating host immune effector cells (viruses and bacteria), and through the release of cytotoxic chemicals.
Mediators of inflammation and immunity can also kill cells through activation of programmed cell death (apoptosis) and through the assembly of membrane channels (membrane attack complex).
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cause -exogenous injury
mechanism-multiple,organs
cells affected- multiple organs
outcome-cell membrane ruptures, tissues death and bacterial infections
necrosis
27
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cause-exogenous or edogenous
mechanism-active programmed process
cells affected-single
cell changes-round up, fracmented cell membrane in tact
outcome-phagocytosis by macrophages
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apoptosis
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Organism establishes parasitic relationship
with host
· Invasion + multiplication of organism =
immune response
· Damage to host:
– Microorganism’s toxins, replication, or indirectly
by competing for nutrient
– By our own immune system
infection
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results when a person eats food
containing toxins that cause illness. Toxins are produced by
harmful microorganisms, the result of a chemical
contamination, or are naturally part of a plant or seafood.
Some bacteria cause an intoxication. Viruses and parasites do
not cause foodborne intoxication.
– Bacteria: Clostridium botulinum, Staphylococcus aureus, Clostridium
perfringens, and Bacillus cereus.
intoxication
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are substances that
typically cause fever
Bacteria
Cytokines
(‘pyrogenic’):
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Local infection spreading into the lymphatic
system
– Lymphangitis
– Moves towards local lymph node
red streak
32
Definition: adverse conditions that cause a cellular response that remains within the
range of homeostasis
– Injury stops cell returns to it’s original steady state
Caused by brief hypoxia (deficiency of oxygen), brief anoxia (total lack of oxygen) or
low concentration of toxins
Reversible cell injury
Cell’s response to exposure to low doses of
toxins, brief hypoxia or anoxia
– Cellular swelling (hydropic changes – swelling of
cytoplasm and cytoplasmic organelles)
■ A. Normal microvilli
■ B. Swollen microvilli
■ C. Invagination of the cell membrane leading to
formation of membrane-bound vacuoles
■ D. Swollen mitochondria and dilated RER
■ E. Loss of intercellular contact
– Changes in cell membrane permeability
■ Na+/K+ ATPase pump
– Cell returns to original steady state with cessation of injury
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Due to cells exposed to heavy doses of toxins,
anoxia or severe or prolonged hypoxia
– Will eventually lead to cell death
Irreversible cell injury
1.Caused by heavy doses of toxins, anoxia and prolonged hypoxia
2.Causes loss of cell integrity and rupture of the cell membrane
3.Dead cells release their contents (especially cytoplasmic enzymes)
into extracellular fluid (blood)
– measured through laboratory blood tests – something is really wrong!
34
Causes of antibiotic resistance
Antibiotic Overuse – creation of ‘superbugs’ – antibiotic-resistant organisms
Methicillin-resistant Staphylococcus aureus (MRSA)
Multi-drug resistant Mycobacterium tuberculosis
Vancomycin-resistant Enterococci
Multi-drug resistant Pseudomonas aeruginosa
Fluoroquinolone-resistant Clostridium difficile
Antibiotic Resistance – Other Factors
Increased travel/exposure – with globalization
TB on the rise; 2nd leading cause of death due to infectious disease worldwide Susceptible sub-populations:
Kids in daycare
Aging
Hospital populations
3 rd world poverty – stress, poor nutrition, close quarters (easy spread), lack of medical care
-use in agriculture
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Signs and symptoms – know what they are
| Signs and Symptoms of Infectious Diseases
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Many and varied
Can be systemic (fever) or local (pus)
Depends on:
– Etiologic agent
– type and virulence
– System affected
– Health of the individual
Common Systemic Signs & Symptoms
Fever Chills Sweat Malaise Nausea Vomiting Change in leukocyte type and/or number Enlarged lymph nodes Possible cognitive changes in the elderly
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36
many types and variety of causes of rash
FYI Common Rashes with Infections
Maculopapular eruptions: – Measles, Rubella, Fifth Disease, Roseola
Nodular lesions: – Streptococcus, Pseudomonas
Diffuse erythema: – Scarlet Fever, Toxic Shock Syndrome
Vesiculobullous eruptions: – Varicella, Herpes zoster
Petechial purpuric eruptions: – Epstein Barr Virus
37
-Can be associated with many infectious diseases, not just sepsis
Easily palpated – Cervical – Inguinal – Axillary Other reasons for inflamed lymph nodes: – Cancer – Rheumatoid Arthritis – Medications
− Lymphangitis
38
local infection spreading into the lymphatic system – Lymphangitis – Moves towards local lymph node
red streak
39
−- Secondary to an infection
Usually from: – Hemolytic Streptococcus and/or Staphylococcus
Lymph nodes most often affected: – Submandibular – Cervical – Inguinal – Axillary
sepsis
40
why no fever with aging?
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– Impaired thermoregulatory system
– Masking effects of drugs
1 st symptoms of infection in elderly may be:
– Confusion
– Memory loss
– Delirium
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41
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An organism that elicits a pathologic response in the
host
· Depends on:
· Site of invasion
· Number of pathogens, and virulence
· How well they disseminate in host
· IMMUNE STATUS OF THE HOST
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pathogen- chain of transmission
42
An environment in which an organism can live and multiply
Animal, plant, soil, food, organic substance
Humans
Human and animal reservoirs can be symptomatic or asymptomatic
A reservoir
43
pathogens that don’t cause
disease in people with intact immune systems, but can
cause devastating disease in hospitalized or
immunocompromised people
Opportunistic pathogens:
44
– refers to the potency of the pathogen
in producing sever disease and is measured in
case fatality rate
Virulence
45
Originating or taking place in a hospital, acquired
in a hospital, especially in reference to an
infection.
– A.k.a. Hospital acquired infections (HAI)
– Most common are UTIs (from catheters or
urologic procedures), blood infections
(from IV catheters or surgical wounds), and GI
infections
Nosocomial infections
46
where the organism leaves the reservoir
Corresponds to entry point on next host
Examples:
– Respiratory droplets, blood, vaginal secretions,
semen, tears
– Urine, feces
– Open lesions, pus
portal of exit
47
Mode/Mechanism of Transmission
HOW THE ORGANISM GETS FROM INFECTED HOST TO NEW HOST:
· Contact – directly or indirectly.
– Direct = physical contact Indirect= via an inanimate intermediate object, called a fomite.
– Ex. Intercourse - HIV vs. touching a handrail – enteric pathogens
· Airborne – disease-causing organisms float on air currents in
the room. Often propelled from respiratory tract through
coughing/sneezing.
– Ex. TB, Chickenpox
· Droplet – different then airborne because they do not remain
suspended in air but fall within 3ft of course. Produced by
coughing/sneezing.
– Ex. Influenza
· Vehicle – occurs when infectious organisms are transmitted
through a common source to many potential susceptible hosts.
– Ex. Salmonella in contaminated food
· Vector –involves insects and/or animals that act as
intermediaries between 2 or more hosts
– Ex. Lyme disease via Black-legged or Deer Ticks
48
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Where the pathogen invades/enters:
Ingestion
Inhalation
Bites
Contact with mucous membranes
Percutaneous
Transplacental
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portal of entry
49
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FACTORS:
Age, sex, ethnicity
Health & nutrition
Hormonal balance
Co-morbidities
Living conditions
Personal behaviours (drug use, hygiene, diet,
sexual practices)
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Host Susceptibility
50
smallest, RNA or DNA covered with proteins – Antibiotics don’t help – Antiviral meds only moderately effective · Entirely dependent on host · Some anti-viral meds are specific – Acyclovir - ’s DNA replication
virus
51
Very small self-replicating bacteria with no cell wall, dependant on host for nutrition ·
Mycoplasmas
| Eg. M.hominis; M.pneumoniae
52
Single celled organisms with cell wall;
independent
· Replicate by growing and dividing in half – they can do this in any tissue ·
Classified by shape (spherical-cocci, rod-shaped - bacilli, spiral-shaped - spirochetes), staining (Gram positive/negative), motility, spores, O2 /nonO
bacteria
aerobic and anaerobic
example-normal gut flora-anaerobic
– Staphlococcus aureus is aerobic (lungs, skin)
53
Small obligate intracellular parasites – non-motile gram negative bacteria
· Primarily animal pathogens that produce disease in humans
· Transmitted via insect bites (tick, flea, louse, mite) · Require host for replication · i.e. Q Fever (Coxiella); “Trench Fever” carried by lice (Rochalimaea)
Rickettsiae
54
Smaller than bacteria but larger than viruses
– Obligate intracellular - Dependent on host for replication
– Always contain both RNA and DNA (unlike viruses) – Susceptible to antibiotics – curative - Most common STD - Leading cause of P.I.D. - Leading cause of preventable blindness in neonates
Chlamydiae
55
-large, multicellular organisms that are generally visible to the naked eye in their adult stages. · can be either free-living or parasitic in nature. · In their adult form, helminths cannot multiply in humans.
Helminths (worms)
There are three main groups of helminths:
– Flatworms (platyhelminths) – these include the trematodes (flukes) and cestodes (tapeworms).
– Thorny-headed worms (acanthocephalins)
– Roundworms (nematodes)
– the adult forms of these worms can reside in the gastrointestinal tract, blood, lymphatic system or subcutaneous tissues.
56
Unicellular organism that produce hyphae (filamentous outgrowths) · Contain nuclei (eukaryotic) · Cell walls · Yeasts or molds · Reproduce by budding off · Eg. Candida albicans
Fungi (yeast/mold)
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Single cells or groups of cells · Motile, free living in moist environments · Cell membrane, no cell wall · Divide similar to bacteria · Eg. Giardia
protozoa
58
Inflammation of a lymph vessel
− Lymphangitis -
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Inflammation of one or more lymph nodes
− Lymphadenitis -
60
Increased lymph fluid in the tissues
− Lymphedema -
61
- Enlargement of the lymph nodes
− Lymphadenopathy
62
Four cardinal signs of inflammation (Celsus 30 BC-38 AD) must know!
Heat (calor)
Redness (rubor)
Swelling (tumor)
Pain (dolor)
Loss of function (function laesa - added later in 1900
63
Five classical signs of inflammation
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(Acronym – SHARP or PRISH)
Swelling
Heat
Altered Function/Immobility
Redness
Pain
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64
- the act or process of forming a margin specifically : the adhesion of white blood cells to the walls of damaged blood vessels.
1 Margination
65
-A condition occurring during inflammation in which leukocytes adhere to the linings of capillaries.
2 Pavementing
Attach to endothelium = pavementing
Protrusions from cytoplasm stick to endothelial cells (especially postcapillary venules)
66
movement of a motile cell or organism, or part of one, in a direction corresponding to a gradient of increasing or decreasing concentration of a particular substance.
4 Chemotaxis
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-a mass of cells and fluid that has seeped out of blood vessels or an organ, especially in inflammation.
5 Exudate
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is extravascular fluid with low protein content and a low specific gravity (< 1.012). It has low nucleated cell counts (less than 500 to 1000 /microliter) and the primary cell types are mononuclear cells: macrophages, lymphocytes and mesothelial cells.
6 Transudate-
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invasion of site with necrosis and pus acute inflammation
7 Suppurative-
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-a blood protein produced in response to and counteracting a specific antigen. Antibodies combine chemically with substances which the body recognizes as alien, such as bacteria, viruses, and foreign substances in the blood.
16 antibodies
71
– several proteins that are activated in a cascade acting on one another Numbered 1-9 (C1, C5..)
All pathways converge to form the Membrane Attack Complex (MAC) (key to destruction of foreign agent)
Bores holes into membranes of microbes or body’s owncells
Fill with fluid → cell death
Complement System
3 pathways that activate the complement cascade
1. Classical pathway – activated by antigen-antibody complexes.
2. Alternative pathway – activated by bacterial endotoxins, fungi, snake venom
3. Lectin pathway – activated by binding of lectin to bacteria
72
Derived from phospholipids of cell membranes
Form leukotrienes and prostaglandins
Polyunsaturated fatty-acid found in brain, muscle and liver
Arachidonic Acid Derivatives
73
increase vascular permeability and promote chemotaxis
Formed through the LOX pathway (lipoxygenase pathway)
Bronchospasm – contract smooth muscles in bronchi
Anaphylactic shock
Leukotrienes –
74
Stimulate vasodilation, increase vascular permeability
Formed through the COX pathway (cyclooxygenase pathway)
Pain and fever
Prostaglandins
75
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Site of wound
Mechanical factors
Size of wound
Presence or absence of infection
Circulation issues
Nutritional and metabolic factors
Age
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Wound Healing
Depends on:
76
Deficient scar formation – poor formation of granulation tissue
Inadequate collagen production can lead to wound dehiscence
Complications of Wound Healing
Excess scar formation
Keloid scar – hypertrophic scars
Can lead to disfigurement and loss of function
77
Immune Response
Innate Immunity (born with)
Nonspecific, protective
No memory
Acquired Immunity
Specific
Has memory
78
Immunity acquired by introduction of an antigen into the host
environmental exposure
Vaccination
Active Immunity
79
Immunity acquired when antibodies produced by one person are transferred to another
trans placental transfer, breast milk, antibody inoculation
passive immunity
80
Major anti-bacterial and anti-viral antibody
most abundant type in blood
Only antibody to cross placenta
Responsible for the protection of the newborn for the first 6 months of life
IgG
81
primary or initial immune response
Largest antibody
stays in blood vessels
IgM
82
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Defends external body surface
Found on mucous membranes
Found in secretions
Saliva
Breast milk
Urine
Seminal fluid
Tears
Nasal fluid
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IgA
83
Controls lymphocyte activation or suppression
| Found exclusively on B-cells
IgD
84
Primary factor in eliminating parasitic infections
Functions during allergic reactions
Activates mast cells to release histamine
Associated with anaphylaxis, hives, allergen induced asthma
IgE
85
ediated by Antibodies (Ab) present in body fluids or secretions
Humoral = body fluids
Blood, Lymph, Interstitial Fluid
Aka. Antibody-Mediated Immunity
B Lymphocytes
Formed in bone marrow
Mature in bone marrow
Differentiate into Memory B-cells or plasma cells
Plasma cells secrete Immunoglobulins (Antibodies) to mount an immune response
Bind Antigen to display it for destruction
Memory B-cells
‘remember’ Antigen after first exposure
Acquired Immunity - Humoral
1. Humoral - B Lymphocytes (B-cells)
Protects against extracellular microbes and their toxins (eg. bacteria
86
All viruses and some bacteria hide inside cells where antibodies cannot reach them
T-lymphocytes can recognize these hidden organisms and destroy the cells
Also implicated in transplant rejection, hypersensitivity reactions, and some autoimmune diseases
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Interaction with antigen→ activates T-lymphocyte to produce specialized Tcells (or sensitized T-cells):
Helper T-cells (75% of all T-cells)
Cytotoxic T-cells
Suppressor T-cells
Memory cells
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2. Cell Mediated – T Lymphocytes (T-cells)
Defense against intracellular microbes (eg. viruses)
87
Lines of Defense
1st line of defense- skin, mucosal, hair, pH barriers
INNATE
2nd line of defense – inflammation
INNATE
3rd line of defense - immune system cells
ACQUIRED
88
Move through the blood vessel wall to inflamed tissue
Phagocytosis → swelling and pain
Emmegration (aka transmigration) (leukocyte rolling across endothelium)
89
Properties of smooth muscle cells and fibroblasts
Contract like muscle cells and secrete cell matrix substances like fibroblasts
Holds edges of damaged tissue together
Myofibroblasts
90
Precursors of blood vessels
Proliferate from small blood vessels at the edges of damaged tissue
Appear 2-3 days after injury. By day 6 new blood vessels are formed
Provide a route for scavenger cells to remove tissue debris and scabs
Allow oxygen and nutrients to flow to injured site
Angioblasts (angio = vessels)
91
Produce extracellular matrix
Fibronectin – provides the glue to hold cells together in wound healing
Collagen – from fibrils in interstitial spaces
fibroblasts
