General Pathology 1-2 (terminology, cell review / cell death and inflammation) Flashcards
what is pathology
study of nature/cause of disease
changes in structure/function
disease
subjective SYMPTOMS/complaints
objective/clinical SIGNS
lab/radiography findings
pathogenic
VECTOR/environment causing disease/pathology
vector
“an organism, typically a biting insect or tick, that transmits a pathogen, disease, or parasite from one animal or plant to another.”
terminology
A- , an-: without
Acro-: extremity
Adeno-: glandular
-Algia: pain
Angio-: blood or lymph vessels
Arthr-: joint
Brady-: slow
Carcin-: crab (cancer)
Cardio-: heart
Cervi-, cervico- : neck
-Cele: swelling, hernia
Cep-, Ceph-: head, brain
Chole: bile
Com-, con-: with, together
Contra-: against
Cyst: hollow organ
Demo-: people
Derm-: skin
Dia-: through
Dys-: difficulty
Ecto-, -ectomy: outside, removal
-Emia: blood
terminology 2
Endo-: inside
Epi- upon
Erythr-: red
Ex-: out of
-Gen: beginning, producing
Glyco-: relating to sugar
-Graphy: recording, writing
Hemo-: blood
Hemi-: one-half
Hepat-: liver
Hydro-: water
Hyper-: above, too much.
Hypo-: below, too little
-itis: inflammation
-Lepsis: seizure (lepsy, leptic)
Leuko-: white
Lipo-: fat
Litho-: rock
-Logy: study
-Lysis, -lyso: destruction
Mega-: large
Meno-: month
terminology 3
Metr-: mother (uterus)
Micro-: small
Myco-: fungus
Mye-: marrow or spinal cord
Myo-: muscle
Narco-: stupor
Necro-: death
Neo-: new
Nephro-: kidney
Neuro-: nerve
-Oid: resembles
-Oma: tumor
Onco-: tumor
Orchi-: testes
-Osis: pathologic condition
Osteo-: bone
Para-: alongside, near
Peri-: around
Phagia-: eating
-Philia: affinity
Phleb-: vein
Phyto-: plants
-Plasia: growth
-Plasm, -plasma: formed
terminology 4
Patho-: disease state
Physio-: nature
Pseudo-: false
Psych-: the mind, mental
Ren-: kidney
-Rrhagia, -rrhea: flowing
Rhino-: nose
Sarco-: flesh
Sclero-: hardness, scarring
Spondy-: spine
-Stasis: stagnation, standing still
Stoma-: an opening; mouth
Syn-, Sym-: with
Thrombo-: clot
Therm-: temperature
-Trophy, -trophic: nutrition, growth
Vaso-: blood vessel
e.g. of prefixes/suffixes put together
Angiogenesis
Metrorrhagia
Hemophilia
Rhinitis
Arthralgia
Hydrocephalus
Macrophages - phagocytosis
diagnosis
id of disease via evaluation of:
signs/symptoms
lab findings
etiology
causative factors
e.g.
congenital
virus
“malignancy”
idiopathic
unknown cause
iatrogenic
iatro = medical treatment
iatrogenic = caused by treatment, and/or procedure/error
pathogenesis
development of disease
terms relating to onset
acute:
sudden/obvious
short term (?)
develops quickly
gradual:
milder condition (?)
developing gradually
insidious:
gradual progression
vague/mild signs
insidious
“proceeding in a gradual, subtle way, but with harmful effects.”
“a gradual progression with vague or mild signs”
manifestations
clinical evidence or effects
e.g.
signs/symptoms
signs = objective indicators=
(e.g. fever)
symptoms = subjective indicators =
(e.g. pain/nausea)
syndrome
collection of signs/symptoms
usually occurs together
in response to certain condition
complications
secondary/additional problems pathological events
arise via/after original disease/pathology
prognosis
outcome of disease
the probable outcome(s) of a disease
“probability or likelihood for recovery”
better definition:
“the likely course of a disease or ailment.”
communicable/contagious
infections that can be spread between people
“Communicable diseases are illnesses caused by viruses or bacteria that people spread to one another through contact with contaminated surfaces, bodily fluids, blood products, insect bites, or through the air.”
cell structure/function
Plasma membrane
Nucleus
Cytoplasm (Cytosol & Organelles)
plasma membrane
recall:
Membrane proteins functions as =
channels,
carriers,
receptors,
ligands,
enzymes,
linkers,
identity markers
cytoplasm
recall:
Consists of cytosol, organelles, cytoskeleton
cytoplasm volume can vary
Nucleocytoplasmic ratio
ratio of nucleus (volume?size?) vs cytoplasm “
Nucleocytoplasmic ratio is higher in
Higher in:
a) undifferentiated adult cells,
b) fetal cells,
c) tumour cells
organelles of cytoplasm
Nucleus
Mitochondria
Ribosomes
Endoplasmic reticulum
Golgi complex
Lysosomes
nucleus?
Separated from the rest of the cell by nuclear membrane
Consists of DNA organized into chromatin
Condenses into chromosomes during cell division
Blueprint for protein synthesis
mitochondria?
Double membrane involved in cellular energy production (internal cristae?)
Energy demanding cells are mitochondrial rich
(liver, nerve, red muscle)
few mitochondria which cells?
undifferentiated cells
many malignant tumor cells
ribosomes
small RNA granules
can be:
a) free floating
b) on RER
involved in protein synthesis
free ribosomes vs RER ribosomes
free ribosomes = proteins for internal cell environment use
RER ribosomes = for “export”
(note “LUXARY proteins”)
luxary proteins
“A protein that is produced only in specialized cells and is not necessary for general cell maintenance, unlike the so-called housekeeping proteins.”
endoplasmic reticulum
membranes continuous with plasma membrane (?) and nuclear membrane
rough ER
involved in protein synthesis; studded with ribosomes
smooth ER
involved in catabolism of drugs, hormones, nutrients
no ribosomes
“associated with the production and metabolism of fats and steroid hormones.”
golgi apparatus
Adjacent to nucleus
membrane bound cisternae
modifies, sorts and packages macromolecules such as proteins and lipids before their secretion
golgi body and proteins before secretion
“The Golgi complex plays a central role in protein secretion by regulating cargo sorting and trafficking”
lysosome?
digestive organelle
lytic enzymes
Fuse with vesicles to digest material
what does lysosome digest?
E.g. worn out structures, bacteria, etc.
lyososomes and lysis
Can release its contents into the cell to lyse cell
why lysis?
(worn out, damaged, too many, infected, etc.)
cell projection types (PASSIVE PROJECTIONS)
microvilli
(no energy required)
FUNCTION??
Increase cell SA
cell projections (ACTIVE PROJECTIONS)
require energy
Cilia
Flagella (flagellum)
cilia
Cilia:
numerous, short, hairlike projections
move substances across the surface of the cell
flagella (flagellum)
single, long projection
functions to move the cell (sperm)
integration
for homeostasis
bringing together various parts –> FUNCTION AS WHOLE
three types of integration
Autocrine
Paracrine
endocrine
Autocrine stimulation (type of integration)
secretes substance that stimulate itself
SIMPLEST
Paracrine stimulation (type of integration)
secretes a substance that stimulates a nearby cell
endocrine stimulation (type of integration)
release substance into the bloodstream
then stimulate distant cell
Highest form of integration?
endocrine stimulation
endocrine stimulation can involve cells of _____
cells of anatomically distinct organs
causes of cell injury?
Hypoxia / ischemia / anoxia
Physical agents (temp/vibration/radiation)
Mechanical damage (trauma)
Abnormal metabolite accumulation
Fluid or electrolyte imbalance
pH imbalance
other causes of cell injury
Chemicals (heavy metals/drugs)
Microbiological agents (bacteria/viruses)
Immunological reactions (autoimmune/host cells)
Genetic defects
Nutritional imbalances
Aging
reversible cell damage
Within range of homeostasis
Membrane left relatively intact (pumps)
Mitochondria able to sustain energy demands
Mild and/or short-lived
Cell returns to its original state
pumps intact?
No Na+K+ pumps puming Na+ out?
= cell swells, and membrane ruptures = lysis
irreversible cell damage?
Structure/function of cell
Decrease energy production
Decrease metabolism
Decrease in pH
irreversible cell damage?
nucleus
Shrinking, fragmentation, lysis (nucleus)
irreversible cell damage?
lysosomes
Can burst releasing degrading enzymes and increase cell damage
irreversible cell damage?
plasma membrane
Extensive plasma membrane damage
irreversible cell damage?
Accumulation of amorphous, Ca-rich densities in the mitochondrial matrix
cellular adaption
cells adapt their growth/differentiation
e.g. normal adaptations
breast/uterine growth during pregnancy
when tissue modify?
modified frequently in response to hormonal stimulation, environmental changes, irritation
atrophy
decrease in the size of cells
resulting in reduced tissue mass
caused by poor nutrition, aging, immobility
i.e.
whole organ, or cellular (?)
atrophy e.g.
Decreased demand, oxygen, nutrients, nerve innervation. Persistent cell injury
hypertrophy
increase in the size of individual cells
resulting in enlarged tissue mass
hypertrophy e.g.
eg.
Striated muscle cells – working out.
Cardiac muscle – cardiovascular disease
hypertrophic cardiomyopathy
.
hyperplasia
increased number of cells
resulting in enlarged tissue mass
can occur in conjunction with hypertrophy
hyperplasia e.g.
e.g. endometrial thickening of the uterus
metaplasia
when one mature cell type is replaced by a different mature cell type
(can be pathological or occur under regular circumstances)
e.g. ciliated columnar epithelia of the respiratory tract changes to stratified squamous epithelia
(IN SMOKERS)
endometrial hyperplasia
Endometrial hyperplasia develops when a woman has an imbalance of estrogen and progesterone.
There are a number of reasons this can occur: Having irregular menstrual periods, being obese, or having polycystic ovary syndrome (PCOS) may interfere with ovulation, which reduces progestin exposure.
benign prostate hyperplasia
.
dysplasia
“cells of a tissue vary in size and shape, large nuclei are present and the rate of mitosis increases; may indicate a precancerous state”
intracellular accumulations
overload of various metabolites/exogenous material
OR
prevention of excretion of metabolic byproducts
intracellular accumulations via ____
overload,
underutilization,
underexcretion
intracellular accumulations e.g.
Black Lung (anthracosis) – accumulation of coal particles
Fatty liver disease (alcoholics or nonalcoholics “) – damage to liver cells, cause decrease in lipoprotein production, therefore an increase in lipid storage
aging
complex adaptations and irreversible cellular events
associated with impaired wound healing (?)
Over 300 theories
E.g.
wear-and-tear, genetic hypotheses, telomere aging clock theory and free radical theory
PHARMACOLOGY LECTURE 1 ***
..
language of pharmacology
how are drugs named?
drug classificaitons, uses, side effects
pharmacokinetics and pharmacodynamics
…
how are drugs administered?
how are drugs processed in body?
…
why do massage therapists need to know how medications work?
.
allopathy?
“the treatment of disease by conventional means, i.e., with drugs having opposite effects to the symptoms.”
“Also called biomedicine, conventional medicine, mainstream medicine, orthodox medicine, and Western medicine.”
why MT familiar with pharmacology?
1) clients combine allopathic therapy with Complementary therapy (alternative “ ?)
2) drugs can interfere with physiological response of Massage & hydrotherapy
3) some medication is contraindication of massage and/or hydrotherapy
4) minor changes in Tx depending on drug / drug delivery (?)
pharmacology define
study of action of chemicals on living organisms
produce biological effects
pharmacology includes
pharmacokinetics
pharmacodynamics
pharmacy
toxicology
pharmacokinetics
What the body does to the drug
pharmacodynamics
What the drug does to the body
pharmacy
“the science or practice of the preparation and dispensing of medicinal drugs.”
toxicology
noun: toxicology
1.
the branch of science concerned with the nature, effects, and detection of poisons.
2.
the measurement and analysis of potential toxins, intoxicating or banned substances, and prescription medications present in a person’s body.
what is pharmacokinetics
“what the body does to the drug”
How the body absorbs, distributes, metabolizes, and eliminate the drug
How long the body takes to accomplish this process, and the drug levels the body is exposed to as a result of this process
what is pharmacodynamics
“what the drug does to the body”
Does the drug mimic normal physiological processes or inhibit processes
This is defined in the “mechanism of action” of the drug
mechanism of action of drug
“In medicine, a term used to describe how a drug or other substance produces an effect in the body.”
E.g. of why RMT needs to know effects of drugs when relevent
client taking pain medication
asks for deep work
is bruised and in more pain the next day
therefore, therapist should know what medication is and what it does to body
E.g.
how effects soft tissue, recovery, or sensory feedback
what should massage therapists know?
a basic understanding of the actions and effects of commonly used drugs
ability to research the effects of other medications encountered
knowledge of how massage affects the body’s physiology
ability to apply this knowledge to varying clients
Common pharmaceutical terms and concepts
…
Drug names
Drug classifications
Uses or indications
pharmacodynamic terms (effects of medications, “Mechanism of action”)
pharmacokinetic terms (half-life, onset of action, bioavailability)
..
how are drugs named?
via:
generic name
or
brand (trade) name
generic name
term that refects chemical structure of drug
assigned by international committee
same around the world
E.g.
Diazepam
= generic name for…
7 chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1,4-benziodiazepin-2-one (C16 H13 CIN2 )
brand (trade) name
formulation is assigned a brand name by manufacturing company
doesn’t reflect chemistry of drug
drug is developed, researched, tested, and produced for sale
i.e. drug manufacturing company
E.g.
Ibuprofen = generic name
brand name = Advil, Motrin, etc
generic medications
generic drug companies produce the medication
cheaper than brand name version
meet FDA requirements
concerns about effectiveness vs brand name (?)
possibly not as effective as “original” (?)
when generic medication?
After a patent expires on a drug, generic drug companies may produce it
drug classifications
non-prescription drugs
prescription drugs
restricted and controlled drugs
other drug classifications
therapeutic properties (action/effect on body)
action or effect on body system
chemical structure
therapeutic properties
describes the effect that the drug has on the body
E.g.
anti-hypertensive to reduce blood pressure
action or effect on specific body system
describes the body system that the drug affects
E.g.
central nervous system stimulant
chemical structure
escribes basic chemical or pharmacologic properties of the drug
E.g.
beta-blocker
what if client does not remember name of drug?
they will know what the drug is used for
can use knowledge of general class of drugs to alter treatment
or
further research drug
Uses/indications for drug
list of diseases/disorders drug is officially recommended for
by
Health Canada
what if a drug helps a condition, but Health Canada has not approved the use for “
There may be some conditions that the drug has shown benefit for
ut Health Canada has not approved use of the drug for “
E.g.
insufficient trial data
contraindications for a drug
disease/disorder that the drug has a negative effect on
should not be prescribed to a client with that condition
(Pharmacodynamics) effects of medication based on
1) Therapeutic effects
2) side effects or adverse effects
3) unpredictable effects
Factors that influence Effects
dosage,
age,
gender,
lifestyle,
pathologies
1) Therapeutic effects
desired effect which is intended to help the user get better
2) side effects or adverse effects
undesirable reactions:
can be b/c of “too much” of therapeutic effect
E.g.
hypotension for hypertension drugs
can be unrelated to therapeutic effect
E.g.
stomach ulcers, GI irritation via Aspirin
can also be via interaction of multiple drugs
side effects or adverse effects via
1) too much therapeutic effect
2) unrelated effect
3) via interaction of multiple drugs
3) unpredictable effects
two types:
a) allergic/hypersensitive reactions
b) idiosyncratic reactions
a) allergic / hypersensitive reactions
can be mild
E.g.
(hives, joint pain, fever)
can be severe
E.g.
anaphylaxis
b) idiosyncratic reactions
unexpected or highly unusual effects
occur in small number of people
important note
client’s primary complaint might be as a result of a drug side effect
should monitor patient symptoms
be alert for unusual
be alert for changes
vs.
massage tx
pharmacodynamics (Mechanism of action)
..
how do drugs create changes?
DRUGS DO NOT create new functions
drugs alter existing cellular activities
Mechanism of action occurs via
one or a combination of the following:
a) Combining with specific cellular receptors
b) Chemically altering body fluids
c) Chemically altering cell membranes
d) Interacting with extracellular enzyme systems
a) Combining with specific cellular receptors
binding to receptor can alter cellular function
E.g.
benzodiazepines binds to a neurotransmitter receptor
b) Chemically altering body fluids
E.g.
antacid to neutralize excess stomach acidity and reduce or prevent digestive discomfort
c) Chemically altering cell membranes
E.g.
alter electrical stability
alter responsiveness to stimuli
can influence the cell’s permeability
I.e.
speeding up / slowing down of ions into/out of cell
d) Interacting with extracellular enzyme systems
enzyme?
protein molecule that facilitate/catalyze chemical reactions of all cells
E.g.
NSAIDs alter pain by blocking the activity of enzymes in the inflammatory response
(Pharmacokinetics) Half-life
time it takes body to reduce concentration of drug to 50%
via metabolism/elimination
E.g. 100mg dose of drug with 20 minute half-life
3.125mg after 100 minutes
(Phamarcokinetics) onset of action
duration of time it takes for drug to become effective
onset of action can be determined by
how was the drug administered/taken?
E.g.
IV versus orally
why onset of action important to know?
can help determine schedule of Massage therapy
(pharmacokinetics) bioavailability
amount of drug that enters systemic circulation
amount available to produce effects
***also determined via how drug is administered/taken
E.g.
50mg of a drug taken orally and bioavailability is approximately 50%,
if 50mg administered via injection, bioavailability is 100%
other things that determine bioavailability
doseage/frequency
age
general health
blood thinners, blood thinning and bruising
“Bruises happen when the smallest blood vessels under the skin (capillaries) break and start to leak, causing discolouration. Blood thinners are designed to slow down the blood clotting, so the broken blood vessels take longer to stop leaking, which can lead to a worse bruise or bruising more easily.”
**General Pathology 300 — Class 2 **
.
Cell death 2 types
1) apoptosis
2) necrosis
inflammation?
will discuss:
signs symptoms
pathogenesis
cellular events in inflammation
cells of inflammation
apoptosis
endogenously programmed (mechanism)
initiating event can be endogenous OR exogenous
endogenous vs exogenous
growing or originating from within an organism.
growing or originating from outside an organism.
necrosis
exogenously induced
via irreversible cell injury
E.g.
toxins, anoxia, etc.
4 types of necrosis
coagulative, liquefactive, caseous, fat
1) coagulative necrosis
most common type of necrosis
mechanism?
Cell proteins are altered or denatured
Via inactivation of hydrolytic enzymes in CYTOPLASM –> these prevent lysis of tissue
–>
Note: cytoplasmic hydrolytic enzymes
most common necrosis type?
coagulative necrosis
which cell proteins denature or are altered in coagulative necrosis?
cytoplasmic hydrolytic enzymes that prevent lysis of tissue
characteristic of tissue during coagulative necrosis
tissues retains original form
firm consistency
where is coagulative necrosis typical?
solid internal organs
common cause of coagulative necrosis
anoxia
E.g.
heart attack
2) liquefactive necrosis
dead cells liquefy
via influence of certain enzymes
dissolution of tissues
SOFT/DIFFLUENT tissue
liquefactive necrosis – where most often?
brain
brain cells liquefied
brain becomes soft, fluid-filled cavity
note secondary liquefaction
tissue may undergo LIQUEFACTIVE necrosis after undergoing COAGULATIVE necrosis
“Coagulative necrosis may liquefy”
3) caseous necrosis
special type of COAGULATIVE NECROSIS
w/ limited LIQUEFACTIVE necrosis
hybrid of two types
tissue becomes “CHEESE-like” and yellow-white
Caseous necrosis where?
TUBERCULOSIS
(almost unique to tuberculosis)
caseous necrosis also where?
Some FUNGAL INFECTIONS
caseous necrosis and tuberculosis
Center of a tuberculous granuloma becomes necrotic and the cells fall apart
“granuloma”
“What is a granuloma? A granuloma is a tiny cluster of white blood cells and other tissue. It can appear in your lungs, skin or other parts of your body. Granulomas aren’t cancerous. They form as a reaction to infections, inflammation, irritants or foreign objects.”
granuloma and tuberculosis
“Tuberculosis is the formation of an organized structure called granuloma. It consists mainly in the recruitment at the infectious stage of macrophages, highly differentiated cells such as multinucleated giant cells, epithelioid cells and Foamy cells, all these cells being surrounded by a rim of lymphocytes.”
4) Fat necrosis
special type of LIQUEFACTIVE necrosis
via?
action of LIPOLYTIC enzymes
where?
limited to fat tissue
Esp around pancreas
which necrosis is special type of liquefactive necrosis
fat necrosis
which necrosis type is a special type combining liquefactive and coagulative necrosis
caseous necrosis
mechanism of fat necrosis
pancreatic enzymes
release into fat tissue
degrade fat into:
GLYCEROL
FREE FAs
I.e.
from Triglyceride?
necrosis – miscellaneous term
Gangrene
gangrene
dead tissue
necrotic tissue and secondary changes E.g.
Necrotic tissue can undergo secondary changes such as
E.g.
CALCIFICATION
Also note:
secondary liquefaction
E.g.
liquefactive necrosis after undergoing coagulative necrosis
note frostbite, dry gangrene, and coagulative necrosis – also note ischemic necrosis
ischemic necrosis is a type of coagulative necrosis
“preservation of cellular architecture and protein coagulation”
“Severe frostbite injuries can lead to dry gangrene”
(“lack in blood supply and oxygen”)
“Frostbite is a cold-induced injury of tissue characterized by freezing and ischemic necrosis.”
apoptosis
programmed cell death
under normal conditions
may occur when:
A) abnormal cell development
B) excessive cell numbers
C) injured cells
D) aged cells
apoptosis – what happens?
cells “self-destruct”
appear to digest itself
disintegrate
I.e.
LYSIS
which cell death type is active
apoptosis
apoptosis important facts
active
requires energy
regulated
requires specific genes/enzymes
mechanism is endogenous (endogenously programmed)
intiating event can be endogenous/exogenous
affects single cells
I.e.
mechanism that operates at a single cellular level
apoptosis is normal development (e.g. formation of digits)
lack of apoptosis can cause pathology
E.g.
important in formation of digits
syndactyly
occurs when digits fused together (e.g. in hands/feet)
inflammation 5 signs
swelling
heat
redness
pain
(occasionally) loss of function
inflammation
“to set on fire”
body’s nonspecific response to tissue injury
E.g.
Appendicitis, laryngitis, pancreatitis, mastitis, etc.
inflammation, facts
biological response of vascular tissues to harmful stimuli
E.g.
pathogens, damaged cells or irritants
inflammation function
protective attempt by the organism to remove/localize the injurious stimuli
initiate the healing process for the tissue
why inflammation important?
Without inflammation wounds and infections would not heal and further destruction of tissue would compromise survival of organism.
when inflammation occur?
cut, allergy, bite, infection, burn, etc.
infection and inflammation
With infection, a microorganism is present
signs and symptoms of inflammation
symptoms:
pain/tenderness
signs:
redness, swelling, heat, loss of function
non-specific symptoms of inflammation
(ESP w/ SYSTEMIC INFLAMMATION – possibly when not visible?)
fatigue
weakness
decreased appetite
aching
PATHOGENESIS OF INFLAMMATION
1) changes in circulation of blood
2) changes in vessel wall permeability
3) release of SOLUBLE MEDIATORS OF INFLAMMATION (SMIs)
4) cellular events
1) changes in circulation of blood
body’s first response to injury
“Mechanical stimulus stimulates nerves that transmit signals to smooth muscle cells on arterioles”
“Constriction followed by relaxation of sphincter”
Blood rushes into capillaries leading to redness, swelling, warmth… (hyperemia)
Blood flow in dilated capillaries is slow leading to congestion
Sludged erythrocytes form stacks (rouleaux) impeding circulation
WBCs are marginalized and become attached to endothelium (pavementing)
what happens when blood rushes into capillaries
redness, swelling, warmth… (hyperemia)
why congestion in capillaries?
Blood flow in dilated capillaries is slow leading to congestion
what do red blood cells form in dilated capillaries?
Sludged erythrocytes form stacks (rouleaux) impeding circulation
“ROULEAUX”
what happens in WBC in dilated capillaries?
WBCs are marginalized and become attached to endothelium
(PAVEMENTING)
2) changes in vessel wall permeability
due to:
Increased pressure inside the congested blood vessels
Slowing of circulation
Adhesion of leukocytes and platelets to endothelial cells (PAVEMENTING)
Release of soluble mediators of inflammation (SMIs)
3) release of SOLUBLE MEDIATORS OF INFLAMMATION (SMIs)
Plasma derived and cell derived
Plasma derived must be activated
Biochemically heterogeneous
Multifunctional and thus have numerous effects on blood vessels, inflammatory cells, etc.
SMIs list
a) Histamine
b) Bradykinin
c) Complement system
d) Arachidonic Acid Derivatives
a) histamine
BIOGENIC AMINE
Released from platelets and mast cells
Provokes contraction of endothelial cells of blood vessels
Leads to formation of gaps
Increases blood vessel permeability
Allows fluids to exit into interstitial spaces
Occurs quickly
Histamine is rapidly inactivated by histaminase
Immediate transient reaction
what does histamine do to BC permeability
increases
“formation of gaps” (??)
allows fluid to go to interstitial spaces
histamine timing
occurs quickly
rapidly inactivated
via
HISTAMINASE
“IMMEDIATE TRANSIENT REACTION”
where histamine released from?
Released from platelets and mast cells
b) Bradykinin
Plasma protein
Similar effects as histamine but occurs at a slower pace
Formed in the plasma through activation of Hageman factor or coagulation factor XII
Incites pain
NOTE THAT CLOTTING FACTOR xii IS ACTIVATED VIA PLATELETS VIA INTRINSIC PATHWAY OF BLOOD CLOTTING – COAGULATION PHASE (STEP IN HEMOSTASIS)
I.e.
inflammation when clotting is needed
Bradykinin vs Histamine timing
Bradykinin effects occur at slower rate
which SMI incites pain?
Bradykinin
which plasma protein activates Bradykinin?
AKA Hageman factor
COAGULATION FACTOR XII (clotting factor 12)
plasma protein
c) Complement system (SMI)
group of plasma proteins
released via LIVER
circulate in INACTIVE form
activate in cascade (activate one another)
Numbered C1 to C9
occuring via 3 pathways:
Classical pathway
Alternative pathway
Lectin pathway
activation leads to formation of active fragments
(e.g. C3a)
activation leads to formation of intermediate complexes
(e.g. C567)
activation leads to terminal membrane attack complexes
(e.g. MAC)
where are complement system plasma proteins created?
produced by LIVER
how to complement system plasma proteins circulate?
in INACTIVE form
how are they numbered?
C1 to C9
which three pathways activate complement system proteins?
Classical pathway
Alternative pathway
Lectin pathway
what are three ways complement system proteins can activate?
formation of biologically active fragments (E.g. C3a)
formation of intermediate COMPLEXES (E.g. C567)
formation of terminal MEMBRANE ATTACK COMPLEXES (E.g. MAC)
MAC mechanism (membrane attack complex)
“MAC destroys cells by boring holes in plasma membrane”
MAIN FUNCTION OF ACTIVATED COMPLEMENT DERIVATIVES
OPSONIZATION
ANAPHYLAXIS
CHEMOTAXIS
CELL LYSIS
opsonization
“Antibody opsonization is a process by which a pathogen is marked for phagocytosis.”
opsonin
“any of various proteins (as complement or antibodies) that bind to foreign particles and microorganisms (as bacteria) making them more susceptible to the action of phagocytes.”
anaphylaxis
histamine release with increased vessel wall permeability
“an acute allergic reaction to an antigen (e.g. a bee sting) to which the body has become hypersensitive.”
anaphylactic shock
“an extreme, often life-threatening allergic reaction to an antigen to which the body has become hypersensitive.”
chemotaxis – general definition
“Chemotaxis is the movement of a cell or organism in response to a chemical stimulus. This phenomenon is commonly seen in bacteria and other single-celled organisms, which use chemotaxis to navigate towards nutrients or away from harmful substances in their environment. Chemotaxis is an important mechanism for the survival and behavior of many organisms.” (AI)
“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.”
chemotaxis
migration of leukocytes
cell lysis
via MAC
d) ARACHIDONIC ACID DERIVATIVES (SMI)
Arachidonic acid
derived from phospholipids of cell membranes
via 2 pathways:
LIPOXYGENASE PATHWAY
&
CYCLOOXYGENASE PATHWAY
2 pathways for metabolism of arachidonic acid (derivatives)
LIPOXYGENASE PATHWAY
&
CYCLOOXYGENASE PATHWAY
lipoxygenase pathway
formation of:
Leukotrienes
– promote chemotaxis and incr. vasc. permeability
Lipoxins
– inhibit chemotaxis
cyclooxygenase pathway
formation of:
Prostaglandins
– cause vasodilation, vascular permeability, mediate pain and fever
–> Prostacyclin
– counteracts thromboxane
Thromboxane
– platelet aggregation, thrombosis, vasoconstriction
thrombosis
“Thrombosis is a blood clot within blood vessels that limits the flow of blood.”
4) CELLULAR EVENTS (FINAL POINT IN “PATHOGENESIS OF INFLAMMATION”
emigration of leukocytes
NOTE:
Increased permeability of vessel wall lasts up to several hours
Accompanied by leakage of fluid into interstitial spaces
Leads to formation of edema
Emigration of cells across vascular wall leads to formation of exudate
4) CELLULAR EVENTS (phagocytosis)
PMNs (polymorphonuclear neutrophils)
—> Lose their mobility —> act as scavengers
Active uptake of bacteria/cellular debris
often PMNs die in their fight with bacteria
The cells of inflammation****
1) Neutrophil (most common)
2) Eosinophils (2-3%)
3) Basophils (1%)
4) Macrophages
5) Platlets
1) Neutrophils (Polymorphonuclear neutrophils –> PMNs)
most numerous (of circulating WBCs)
“Multi-segmented” nucleus (up to 5)
They are first to appear in acute inflammation
characteristics:
mobility, bactericidal activity, phagocytosis, produce and release cytokines
cytokine
“any of a number of substances, such as interferon, interleukin, and growth factors, which are secreted by certain cells of the immune system and have an effect on other cells.”
“From the Greek cyto (cavity or cell) and kine (movement), cytokines are proteins involved in cell signaling and function as immunomodulating agents.”
which cell most numerous circulating WBC?
PMNs (polymorphonuclear neutrophils)
which cell first to appear in acute inflammation?
PMNs
which cell mutliple nuclei (“multi-segmented”) – up to 5
PMNs
2) EOSINOPHIL
2-3% of circulating WBCs
characteristics:
slower mobility
slower to react to “chemotactic” stimuli
–>
see “chemotaxis”
ALSO SEGMENTED NUCLEUS (2)
prominent in:
allegic reaction
inflammatory response to parasites
eosinophil percentage
2-3% of circulating WBC
eosinophil rate of action
slower mobility
slower reaction to chemotactic stimuli
eosinophil # of nuclei
2 (multi-segmented)
eosinophil common in
allergic reactions
inflammatory response to PARASITES
PMNs common in
acute inflammation (first to appear)
3) BASOPHILS
less than 1% of ciruclating WBC
present in inflammatory reactions
prominent in allergic reactions mediated by immunoglobulin E (IgE)
Non-segmented nucleus
CYTOPLASMIC GRANULES
LARGER THAN PMNS (big basophils)
structurally related to Mast Cells
immunoglobulin define
“any of a class of proteins present in the serum and cells of the immune system, which function as antibodies.”
globulin
“Globulins are a group of proteins in your blood. They are made in your liver by your immune system.”
which WBC less than 1% circulating WBC
Basophil
which WBC larger than PMNs
slides say larger than PMNs
google says slightly smaller than PMNs
Type Approx. % in adults Diameter (μm)
Neutrophil 62% 12–15
Eosinophil 2.3% 12–15 (slightly bigger than neutrophils)
Basophil 0.4% 12–15 (slightly smaller than neutrophils)
largest WBC
monocyte
which WBC related to mast cells
Basophil.
basophil segmented or non-segmented nucleus?
non-segmented
basophil cytoplasm
cytoplasm has granules
where are basophils MOST COMMON
Most common in allergic reactions mediated by immunoglobulin E (IgE)
IgE most common allergies (Immunoglobulin E)
Peanut allergy: Peanut allergy is one of the most common and severe food allergies, and it is mediated by IgE antibodies.
Tree nut allergy: Similar to peanut allergy, tree nut allergy is also mediated by IgE antibodies and can cause severe reactions.
Wheat allergy: Wheat allergy is another common food allergy that is caused by an IgE-mediated response to wheat proteins.
Milk allergy: Milk allergy is a common allergy in infants and young children, and it is caused by an IgE-mediated response to milk proteins.
Egg allergy: Egg allergy is another common food allergy that is caused by an IgE-mediated response to egg proteins.
Fish and shellfish allergy: Fish and shellfish allergy are also common food allergies that are mediated by IgE antibodies.
Insect sting allergy: Insect sting allergy is a severe allergic reaction that occurs when an individual is stung by an insect, such as a bee or wasp, and is caused by an IgE-mediated response to the insect venom.
Hymenoptera venom allergy: Hymenoptera venom allergy refers to an allergic reaction to the venom of insects such as bees, wasps, hornets, and yellow jackets.
Mold allergy: Mold allergy is a common respiratory allergy that is caused by an IgE-mediated response to mold spores.
Dust mite allergy: Dust mite allergy is another common respiratory allergy that is caused by an IgE-mediated response to dust mite allergens.
4) MACROPHAGE
tissue cells
derived from blood MONOCYTES
“are produced by the differentiation of monocytes in tissues.”
BEANSHAPED nucleus
larger than PMN
“Macrophages are generally larger than typical monocytes.”
–> Recall:
Monocyte/macrophage = biggest – but differentiated macrophage = bigger
when macrophage appear at inflammation site?
3-4 days after onset
live long
typical in chronic inflammation
phagocytic/bactericidal
which WBC slowest/quickest?
macrophage slowest & live longest
PMNs quickest reaction
eosinophils slower reaction
which WBC derived from monocytes
macrophage
which WBC bean shaped nucleus
macrophage
which WBC long lived – appear @ infl site after 3-4 days –> typical in chronic inflammation?
Macrophage
5) PLATELETS
what?
fragments of cytoplasm released from MEGAKARYOCYTES in bone marrow
NO NUCLEUS
membrane-bound granules which contain HISTAMINE, coagulative proteins, cytokines, growth factors, etc
OTHER WBCs
LYMPHOCYTES
PLASMA CELLS
are platelets technically considered to be White blood cells?
no nucleus, no genes
Not generally considered to be a white blood “Cell”
cell fragment
what are MEGAKARYOCYTES
A megakaryocyte (mega- + karyo- + -cyte, “large-nucleus cell”)
“LARGE NUCLEUS CELLS”
“a large cell that has a lobulated nucleus, is found especially in the bone marrow, and is the source of blood platelets.”
no nucleus?
platelets
what do platelets contain?
membrane-bound granules –> contain:
HISTAMINE
COAGULATIVE PROTEINS
CYTOKINES
GROWTH FACTORS
other important terminology
EDEMA
transudate
exudate
chemotaxis
Pus
purulent/suppurative
edema
“a localized or generalized condition in which the body tissues contain excessive fluid”
Transudate
the fluid that passes through a membrane; compared to exudate has fewer cells
Exudate
a fluid released from the body with a high concentration of cells and protein
exudate vs transudate
EXUDATE:
“Exudate is fluid that leaks out of blood vessels into nearby tissues. The fluid is made of cells, proteins, and solid materials. Exudate may ooze from cuts or from areas of infection or inflammation.”
TRANSUDATE:
“Transudates are fluids that pass through a membrane or squeeze through tissue or into the EXTRACELLULAR SPACE of TISSUES. Transudates are thin and watery and contain few cells or PROTEINS.”
chemotaxis (see above)
The movement of WBCs in response to the release of chemical mediators
WBCs move up or along the concentration gradient
Requires energy
Active
pus
“protein rich fluid contain WBCs and cellular debris produced during inflammation”
“a thick yellowish or greenish opaque liquid produced in infected tissue, consisting of dead white blood cells and bacteria with tissue debris and serum.”
purulent/suppurative
“forming or containing pus”
purulent vs suppurative
“Not knowing any official difference, I think of purulent as ‘stinky’ and suppurative as ‘oozing’.”
purulent etymology:
“festering” “pus”
