Krafts- General Principles of Homeostasis Flashcards
What is the balancing act in homeostasis?
Pro-clotting (plugs up holes in blood vessels)
Anti-clotting (keeps clotting under control)
What are the three steps to clotting?
Constrict the blood vessel in the region of the hole
form a platelet plug
seal the plug w/ fibrin
Why do blood vessels constrict?
Decrease blood loss
Helps platelets and factors to stick together when they bump into eachtoher
What happens when the platelets form a plug?
proteins are exposed platelets adhere granules release contents platelets aggregate phospholipids are exposed
**this is primary hemostasis!
It would fall apart if fibrin didn’t come next
How does fibrin seal up the plug?
TF is exposed
cascade begins
cascade makes fibrin
fibrin solidifies the plug
**this is SECONDARY hemostasis
How is clotting stopped?
Inhibit coagulation cascade
Lyse portions of clot to keep it down to a reasonable size
What factors inhibit the coagulation cascade?
ANTI-CLOTTING TEAM
TFPI
ATIII
Proteins C,S
What does TFPI do?
shuts off tissue factor (extrinsic) pathway by inhibiting VIIa
What does ATIII do?
Inhibits the serine proteases (IIa, VIIa, IXa, Xa, XIa, XIIa) shuting off all THREE pathways
What potentiates ATIII?
Heparin
What does protein C do?
It is a serine protease which destroys VA and VIIa thereby shutting down coagulation.
What does protein S do?
It is a co factor that helps protein C?
**C is batman, S is robin
What factors are responsible for clot lysis?
tPA
plasmin
What does tPA do?
it binds to fibrin (which is great b/c it keeps it’s action localized to the clot) and converts plasminogin to plasmin
What does plasmin do?
breakes down fibrin into FDPs (split products) which inhibit thrombin and fibrin formation
Are platelets cells?
Not really—they don’t have a nucleus.
What are platelets?
fragements of cytoplasm shed by gigantic precursor megakaryocytes that live in bone marrow
Where are most platelets found?
Most are in the blood (and BM)
but 1/3 are sequestered in teh spleen
What are the two major components of a platelet?
Granules (found in purplish region of granulomere, peripheral region is graunule free= hyalomere)
Membrane
What are the components of a platelet membrane?
phospholipids (coag factors need to bind to be activated)
GP Ia (binds collagen)
GP Ib (binds vWF)
GP IIb-IIIa (binds fibrinogen)
What is found in the granules of platelets?
alpha granules (specific)–fibrinogen, vWF
gamma granules (dense)- serotonin, ADP, Ca2
How do platelets form a plug?
Endothelial damage exposes subendothelial proteins (like collagen)>
attracts platelets>
Platelets stick to subendothelilum via vWF (adhesion)>
platelets change shape and release granule contents>
attracts more platelets>
form temporary plug (aggregation)>
platelets contract and seal vessel wall
Where does TF come from?
“hidden” cells exposed during injury (not normally in contact w/ blood)
microparticles floating in blood
endothelial cells and monocytes (during inflammation)
What should you tattoo on your leg?
THE WHOLE POINT OF THE COAGULATION CASCADE IS TO TURN FIBRINOGEN INTO FIBRIN
What are all the coagulation factors?
enzymes or cofactors
What is the major activator of the extrinsic pathway?
Tissue factor
What happens in the extrinsic pathway?
TF binds to VII>
actiates it>
TF-VIIA complex kicks off coagulation cascade>
Xa>
TFPI turns off TF>
Extrinsic pathway shut down preventing over clotting and thrombosis
What is the main activator of the intrinsic pathway?
Thrombin
The final common pathway consists of what cofactors?
X, V, II (thrombin) and I (fibrinogen)
How do the pathways interact in real life?
- vascular injury exposes TF to blood stream
- coagulation started along extrinsic pathway (make Xa and thrombin along the way)
- Xa turns off extrinsic pathway (through TFPI)
- Thrombin activates the intrinsic pathway
- mush platelet plug is transformed into solid mass by fibrin
What turns on protein C?
Thrombin
Thrombin binds thrombomodulin> complex activates protein C
What are two types of platelet tests?
Count- done by particle counter, 150-450 x 10^9 L
Morphology-size/granulation
What are irregular morphologies seen in platelets?
Normal–have hyalomere and granulomere (w/ granules!)
Hypogranular/agranular platelets
LARGE platelet
Why is bleeding time measured?
to evaluate platelet response to vascular injury
- some platelet disorders have a long bleeding time
How is bleeding time measured?
Inflate blood pressure cuff
make incision
time how long it takes to stop bleeding (2-9 mins usually, longer in children)
What is closure time?
an alternative to bleeding time
Platelet funciton analyzer 100 measures how quickly platelets occlude small holes in a membrane
Closure time is better at detecting what two things?
- better at detecting aspirin related bleeding and vW disease
Why is platelet aggregation measured?
To find platelet function abonormalities
How is platelet function measured?
Add aggregating agents to pt’s sample
see if platelets aggregate
measure DECREASE ins ample turbidity
How do you make your diagnosis by looking at platelet aggregation?
Pattern of response helps you to narrow down diagnosis
NORMAL platelets respond to every aggregating agent.
In platelet disorders, platelets do not respond the same to every aggregating agent.
How do you do a coagulation lab test?
draw blood into citrate tube
spin tube, decant plasma
add reagents to plasma
watch for formation of fibrin
What is prothrombin time?
Plasma+ thromboplastin
Measures extrinsic pathway
VII: what makes it? What does it need? Coumadin effects? Half life?
Made by liver
needs K
decreased by coumadin
SHORT half life
Decreased: VII, X, V, II, I coumadin heparin DIC
leads to increased…
PT (prolonged)
What increases PT?
Coumadin
Heparin
DIC
When should you order a PT?
prothrombin time—NEVER!
order an INR instead
What is an INR?
a corrected PT
internationalized normalized ratio
When should you order an INR?
To assess liver function
monitor coumadin therapy
diagnose DIC*
Assess pre-op status
What is partial thromboplastin time and what does it measure?
Pasma + phospholipid
measures the INTRINSIC pathway
APTT = same thing
What increases PTT?
hemo A hemo B DIC heparin inhibitors
When should you order a PTT?
To investigate hx of abnormal bleeding monitor heparin therapy diagnose DIC diagnose atiphospholipid Ab assess pre-op status
What is thrombin time?
plasma+ thrombin
measures conversion of fibrinogen to fibrin
bypasses intrinsic and extrinsic pathways
What increases TT?
decreased fibrinogen
increased FDPs
When should you order a TT?
When the PTT is prolonged and when you want to rule out fibrinogen problems (rare)
What are the ingredients for a PTT mixing study?
Pooled plasma + pt plasma+ phospholipid
What happens if the PTT corrects?
something is missing– usually a coagulation factor
What happens if PTT doesn’t correct?
Inhibitor present
even though you added a bunch of normal plasma to the mix, the pts plasma still couldn’t clot normally so there must be a problem w/ the pt’s plasma
When should you order a mixing study?
When PTT is prolonged but TT is normal
What is a fibrin degradation protein assay?
Measures FDPs which are the result of breakdown of fibrin by plasmin
VERY sensitive
What causes FDPs to go up?
thrombi
minor clotting
When should you order an FDP assay?
Not to rule in a clot
but to RULE OUT a clot
What does a fibrinogen assay do?
Measures fibrinogen…duh.
What causes fibrinogen to go down?
DIC
Massive bleed
When shouldl you use a fibrinogen level?
To diagnose DIC
to follow pts w/ a massive bleed
