Overview of Hemostatic Systems Flashcards
hemostatic system
ancestral system designed to keep an individual from bleeding
what other systems within the body does the hemostatic system include? (7)
vascular system coagulation system fibrinolytic system platelets kinin system serine protease inhibitors complement system
3 main stages of the hemostatic system
- vasoconstriction of blood vessels
- formation of a platelet plug
- blood clotting which reinforces the platelet plug with a fibrin mesh
what does a balance between procoagulant and anticoagulant forces maintain?
blood in a fluid state and flowing through the vasculature to deliver oxygen to tissues systemically and remove carbon dioxide and toxic waste products
where does the term hemostasis come from
greek words
heme=blood + states
halt= halt from blood
why do you pinch a cut?
to prevent blood flow
decreased blood pressure can lead to which 2 mechanisms?
endocrine mechanism
neural mechanism
endocrine mechanism
ASH, angiotensin 2, aldosterone, EPO released
increase in blood volume
homeostasis restored
neural mechanism
baroreceptors, chemoreceptors stimulated
cardiovascular centers stimulated
general sympathetic activation, release norepinephrine, epinephrine
increase cardiac output
peripheral vasoconstriction, increase blood pressure, decrease venous reserve
homeostasis restored
vasoconstriction
contraction of smooth muscle cells to vessel walls to restrict the loss/flow of blood at site of injury
what is the mechanism of vasoconstriction?
sympathetic nerves trigger reflexive contraction of vascular smooth muscle
what are the other regulatory substances which also affect vascular tone? (3)
serotonin
endothelia-1
histamine
serotonin is made and released by
platelets at neuromuscular junctions
what are the direct actions of serotonin?
vasoconstrictor where present at high concentrations at sites of injury
what are the indirect actions of serotonin?
can act as a vasodilator when stimulates nitric oxide release by endothelial cells
serotonin is also synthesized by serotonergic neurons of the CNS, where it regulates (3)
mood
appetite
sleep
endothelin-1 is made and released by
damaged endothelial cells
endothelin-1 is normally kept in balance by other mechanisms, but when over expressed can contribute to (3)
hypertension
heart disease
other vascular diseases of the heart, lung, kidney, and brain
histamine bind to
one of four different histamine GPCR on GI, uterus, lung, and vascular smooth muscle cells
histamine is produced and released from (2) during
basophils (circulation) and mast cells (connective tissue) during local immune responses
prostacyclin (PGI2) is a
vasodilator
thromboxane A2 is a
vasoconstrictor
PGI2
prostaglandin or eicosanoid
what does PGI2 inhibit?
platelet activation and is also an effective vasodilator (acts to counteract actions of TXA2)
prostacyclin (PGI2) mechanism
Mechanistically, PGI2 binds to the PGI2 receptor which is a Gs protein coupled receptor which signals via adenylyl cyclase to produce cAMP. cAMP activates protein kinase A which promotes the phosphorylation and inhibition of myosin light chain kinase which leads to vascular smooth muscle relaxation and vasodilation.
PGI2 half life
42 seconds and is broken down to a weaker chemical form
where is TXA2 made and released?
by activated platelets and endothelial cells
TXA2 is a
prostaglandin
TXA2 stimulates
activation of new platelets as well as increases platelet aggregation by increasing expression of glycoprotein complex GP2b/3a (fibrinogen receptor) on platelet membranes
TXA2 half life
30 seconds, limits action to near site of production
state of vascular tone
balance between constrictor and dilator influences
what are extrinsic factors? (2)
sympathetic nerves
circulating factors
what increases and what decreases vascular tone?
increase: constrictors
decrease: dilators
vasoconstrictor and vasodilator influences acting on arteries and veins determine their state of
vascular tone
what are intrinsic factors influencing vascular tone? (4)
myogenic
endothelial
local substances
metabolic byproducts or hypoxia
myogenic mechanisms arising from vascular smooth muscle
increase tone, constrict vessels
endothelial factors (2)
nitric oxide (vasodilator) endothelin (increase tone, vasoconstriction)
local factors (3)
arachidonic acid metabolites histamine bradykinin (vasodilator or vasoconstriction)
metabolic byproducts or hypoxia
generally decrease tone (vasodilation)
what are examples of extrinsic factors influencing vascular tone? (2)
angiotensin 2
circulating factors like atrial natriuretic peptide
angiotensin 2
increase vascular tone
circulating factors like atrial natriuretic peptide
decrease vascular tone, vasodilation
what do cell stressors such as ischemia active?
phospholipase A2
what does phospholipase A2 cleave?
arachidonic acid from membrane phospholipids and facilitates the formation of prostaglandins
what are the principle postanoids we focus on? (3)
PGI2
TXA2
PGE2
activated macrophage function (2)
phagocytosis and activation of bacterial mechanisms
antigen presentation
where are macrophages present?
in almost all tissues
macrophages are the mature form of
monocytes
what do macrophages orchestrate?
immune responses and half induce inflammation
what do macrophages secrete?
signaling proteins that activate other immune cells
macrophages are the general — cells in the body
scavenger
what is the activated function of neutrophils?
phagocytosis and activation of bactericidal mechanisms
where are the primary neutrophil cells recruited?
to the site of acute inflammation (PNMs)
what are the most numerous of the phagocytic cells and most important in innate immune responses?
neutrophils
what is the activated function of mast cells?
release of granules containing histamine and active agents
what is histamine a critical factor in initiating?
the immune response mechanisms to fight inflammation
histamine causes
vasodilation
histamine permits entry of cells and proteins into the site of the infection to
engage invading pathogens
what is histamine a mediator of?
itching
what are RBC produced from?
hemocytoblast (stem cell)
do you genotype RBC or WBC?
WBC because RBC are enucleate
platelets are released as
nuclear membrane limited bags filled with granules and vesicles from very large bone marrow cells called megakaryocytic
do platelets gave true cells?
no
platelets are cytoplasmic fragments with purple granules that contains chemicals for
blood clotting
blood clotting chemicals include (5)
enzymes serotonin ca2+ ions ADP PDGF
platelets are usually keep in the — state, but
inactive
molecules secreted by endothelial cells of blood vessels
when activated, what do platelets form?
a temporary plug that helps to seal breaks in blood vessels
inflammation
the body process of fighting against things that harm it, such as infections, injuries, and toxins, in attempt to heal itself
5 cardinal signs of inflammation
pain heat redness swelling loss of function
allergic reaction chemical irritants infection trauma injury burns laceration, cuts, wounds frostbite
acute inflammation
cardiovascular disease neurological disease autoimmune disease rheumatoid arthritis cancer lupus fibromyalgia chronic fatigue syndrom
chronic inflammation
what are the 3 major components of acute inflammation?
vascular changes
cellular events
mediators
vascular changes
increased blood flow (vasodilation), increased vascular permeability
cellular events
migration of leukocytes (mainly neutrophils of PMNs) into the site of injury (cellular recruitment and activation)
mediators
derived from plasma cells and proteins
3 stages of the healing cascade
inflammation
proliferation
remodeling
inflammation
early phase
- neurtophil arrival
- pinoeering
late phase
-monocyte-mnacrophage
proliferation (3)
re-epithelialization
-keratinocyte migration
angiogenesis
- spourting
- endothelial migration
granulation tissue
- fibroblast migration
- fibrin-collagen GT
- glycosaminoglycans proteoglycans
remodeling
- apoptosis
- collagen 3-1
- matrix-mellaproteinase activity
exudate:
high protein (>1.02)
transudate
low protein -alb. (<1.01)
pus
enriched in neutrophils
inflammation and hypersensitivity disease
type 1-4
type 1
anaphylactic
type 2
antibody dependent
type 3
immune complex type
type 4
cell mediated
type 1 inflammation and hypersensitivity diseases (allergy and atrophy)
- Hayfever
- Bee sting
- Allergic Asthma
- Penicillin-prototype
- Codeine•Morphine
- Heat/Cold/UV
- Allergen “skin prick tests”
- Nasal Polyps
- Aspirin
- Parasites (schistosomes “nuked” by IgE armed leukocytes)
type 2 is — dependent
antibody
type 2 cell membrane antigens are altered to
non-self
potential mechanisms of type 2 may be (3)
- Complement mediated lysis of host cells (e.g., Rh incompatibility, blood transfusion, RX drug)
- Antibody dependent cell mediated cytotoxicity (ADCC) without complement as in dealing with schistosomes
- Direct binding by antibody to stimulate the cell
Direct binding by antibody to stimulate the cell (2)
- Blocking Ach receptor at NMJ (Myasthenia gravis)
* TSH receptor – Graves disease
what does type 3 involve?
soluble immune complexes (IgM, IgG, IgA) of antibody and antigen
type 3 only involves
complement binding antibodies
type 3 complexes are spread to
joints/kidneys
type 3 complexes precipitate and activate complement causing
tissue damage
type 4 is an important mechanism to
protect against intracellular pathogens (AIDS patients often get TB)
type 4 is mediated by
T cells rather than by antibody
what is the most important mediator of type 4 reaction?
IFNy
either — or — make cytokines after recognizing MHC2 of APCs
CD4 helper T cells
CD8 cytotoxicity T cells
what is critical for this process?
IL-12
examples of CD4 helper T cells (3)
Mantoux test for TB (tuberculin)
nickel
poison ivy
examples of CD8 cytotoxicity T cells (3)
graft rejection
TB
leprosy
