Hemodynamic Disorders 1 Flashcards
Define Edema
Increased fluid in the interstitial space
Define hyperemia
Caused by increased blood flow
Active
Increased blood volume in tissue
Define congestion
Increased backup of blood
Passive
Increased blood volume in tissue
Define hemorrhage. Describe the development of a bruise. What happens to RBC during a bruise?
Extravasation of blood (leakage)
May cause hematoma (petechia is smallest, ecchymosis is largest)
Bruising: RBC phag and degraded
Hemoglobin→ BILIRUBIN→ HEMOSIDERIN
PURPLE→ GREEN→ BROWN
Define thrombosis
Clotting blood
Define embolism
Downward travel of a clot
Define infarction
Death of tissues w/o blood
Define shock
Circulatory failure/collapse
What is it called when we have fluid (edema) in the thorax?
Hydro-thorax
Pleural effusion
What is it called when we have fluid (edema) in the pericardium?
Hydro pericardium
Pericardial effusion
What is it called when we have fluid (edema) in the perituneum (abdomen)?
Hydro peritoneum
ascites
Define Anasarca
Total body edema
Severe
What maintains homeostasis of fluid in the body?
Vascular hydrostatic pressure
Plasma Colloid Osmotic Pressure (Oncotic pressure)
Define hydrostatic pressure.
the pressure exerted by a fluid at equilibrium at a given point within the fluid, due to the force of gravity
Define oncotic pressure.
the pressure exerted by proteins, notably albumin, in a blood vessel’s plasma that usually tends to pull water into the circulatory system
What 4 possibilities can cause Edema?
Increased Hydrostatic Pressure
Reduced Oncotic Pressure
Lymphatic Obstruction
Sodium/Water Retention
What two factors can cause increased hydrostatic pressure?
Impaired venous return
Arteriolar dilation
What is caused by impaired venous return?
Congestive heart failure (pumping)
Constrictive pericarditis (elasticity)
Venous obstruction or compression
-Thrombosis
-External pressure (e.g. mass)
-Lower extremity inactivity (right heart)
What is caused by arteriolar dilation?
Heat
Neurohumoral dysregulation
What is caused by reduced plasma oncotic pressure?
Protein-losing glomerulopathies (nephrotic syndrome) (low protein)
Liver cirrhosis (ascites) (slow blood flow)
Malnutrition (low protein)
Protein-losing gastroenteropathy (low protein)
How does sodium/water retention occur?
Heart failure→renal hypoperfusion→
increased renin-angiotensin-aldosterone secretion→sodium/water retention
How does edema occur from sodium water retention?
Increased hydrostatic pressure (due to intravascular fluid volume expansion)
Diminished oncotic pressure (due to dilution)
Sodium attracts water, water causes edema
How does a ACE inhibitor and Angiotensin 2 receptor blocker drug lower BP?
ACE promotes conversion of Angiotension 1 to Angiotensin 2
Angiotensin 2 constricts bv, increasing BP and also causes release of aldosterone from adrenal which cause Na/water retention
Blocking will prevent these
How does lymphatic obstruction occur (causing edema)?
Inflammatory
Neoplastic (mass of tissue)
Postsurgical
Post-irradiation
What are the types of edema?
Transudate- results from disturbance of Starling forces (hydrostatic and oncotic)
Exudate- results from damage to the capillary wall
gravity, protein content
Describe the different kinds of Edema.
Subcutaneous (“Pitting”)
“Dependent”-on gravity & position
Anasarca
Periorbital-severe renal disease
Cerebral (closed cavity, no expansion)
Ascites- abdomen
What kind of edema does left heart failure cause?
Pulmonary edema
What kind of edema does right heart failure cause?
Lower body edema
Define normal hemostasis.
Series of regulated processes
that maintain blood in a fluid, clot-free state in
normal vessels while rapidly forming a localized
hemostatic plug at the site of vascular injury
Define thrombosis
the formation of blood clot
(thrombus) in intact vessels or within chambers of
the heart
What 3 elements does hemostasis and thrombosis involve?
Vascular wall
Platelets
Coagulation cascade
What trippers the clotting process to begin? What causes it?
Exposer of the sudendothelial matrix
Caused when the blood vessel is injured and endothelial cells are lost
What effect first occurs when the blood vessel is injury and the matrix is exposed?
Vasoconstriction to stop the bleeding that resulted from the injury
By what 2 mechanisms does vasoconstriction occur in response to injury?
Neurogenic mechanisms- nerves
Release of endothelin (transient)
Is the process of vasoconstriction stable?
No it is transient
Temporary fix requires next step
What is primary hemostasis? Does it result in a stable clot? When does it occur?
Formation of a non stable clot (aggregation of platelets to prevent blood leakage)
After vasoconstriction triggered by exposure of Endo matrix
What are the steps involved in primary hemostasis?
Platelet adhesion (platelets adhere to subendo matrix)
Platelet activation (shape change and platelet granule release)
Recruitment (of platelets)
Aggregation (temporary plug formation)
Describe the shape change and platelet granule release that occurs during the platelet activation step of primary hemostasis.
Shape change- round to flat with spikey protrusions to increase surface area
Granule release- helps with platelet aggregation
1. ADP
2. TXA- thromboxane promotes aggregation
What steps are involved in secondary hemostasis?
What does it result in?
Tissue Factor released (factor 3) binds to factor 8
Translocation of negatively charged phospholipids to platelet surface
Coagulation cascade
Thrombin activated
Fibrin formed, more platelets activated
Strong stable clot formed
What does thrombin do?
Fibrinogen to fibrin
Generates fibrin which polymerizes the clot making it stable
Describe the steps involved in antithrombotic counterregulation.
Bleeding controlled
Counterregulatory mechanisms limit the hemostasis process at the site of injury
What are the counregulatory mechanics that limit hemostasis during antithrombotic counterregulation? Why do we have these?
Clot can impair blood flow if it stays around so we want it gone
Release TPA (tissue plasminogen activator) (fibrinolysis) and thrombomodulin (blocks coagulation cascade) to break down the clot
What do platelets form during injury?
Forms a hemostasis plug that seal vascular defects
What granules do the platelets release primary hemostasis?
α granules:
Coagulation: Fibrinogen, coagulation factor and vWF – Wound healing: Fibronectin, platelet-derived growth
factor (PDGF) and transforming growth factor, &
fibronectin
δ granules (dense bodies):
ADP/ATP, Ca+, histamine, serotonin, epinephrine
What forms the tissue factor that is released during secondary hemostasis?
Platelets and endothelium
How do platelets adhere to the underlying basement membrane ECM following endothelial injury?
primarily through binding of platelet GpIb receptors to vWF
What mechanisms are involved in the activation of platelets?
Secretion of platelet granule contents→
Dramatic changes in shape and membrane composition→
Activation of GpIIb/IIIa receptors
What mechanisms are involved in platelets aggregation?
GpIIb/IIIa receptors on activated platelets form bridging
crosslinks with fibrinogen→
Concomitant activation of thrombin promotes fibrin deposition, cementing the platelet plug in place.
What is Bernard Soulier syndrome?
Blood clot disorder
GPlb on surface of platelets
No aggregation, can’t clot, bleed easily
What is Glanzmann thrombasthenia?
Gpllb-llla complex forms a bridge with fibrinogen and platelets leading to fibrin
Can’t form stable clot
No fibrin
What is von Willebrand disease?
Von willebrand factor binds to Gplb is on surface of platelets
This binding starts platelet aggregation
No aggregation, can’t clot, bleeds easily
What are the 3 mechanisms by which the endothelium naturally prevents clotting when it is not needed?
Antiplatlet
Anticoagulant
Fibrinolytic
Describe the anti platelet properties of the endothelium.
Protection from the subendothelial ECM so it is not exposed
NO, PGI2 (anti aggregation) and adenosine diphosphatase secreted by Endo to inactivate platelets to prevent clotting
Describe the anticoagulant properties of the endothelium.
heparin (blood thinner)-like molecules bind to antithrombin 3 degrades CF 2, 9, 10
Thrombomodulin
Tissue factor pathway inhibitor
Describe the fibrinolytic properties of the endothelium.
tissue-type plasminogen activator (TPA) breaks blood clot
Thrombomodulin binds to thrombin 2, activates protein C which inhibits 5 and 8
What are the 3 mechanisms by which endothelial cells respond to injury?
Activation of platelets
Activation of clotting factors
Antifibrinolytic factors
What factors can induce injury to the endothelium?
Infectious agents
Hemodynamics
TNF
IL-1
What occurs during the activation of platelets during endothelium injury?
Von willebrand factor on exposed ECM binds to Gplb on the surface of platelets
What occurs during activation of clotting factors after endothelial injury?
Tissue factor
Coagulation factors IXa and Xa
What occurs during antifibrinolytic phase of endothelium injury?
Plasminogen activator inhibitors (PAIs) inhibits TPA to keep clot intact
What is the coagulation cascade?
Successive series of amplifying enzymatic reactions
Proenzyme is proteolyzed to become an active enzyme,
which in turn proteolyzes the next proenzyme in the
series
What are the 2 pathways of the coagulation cascade? What is their rate?
Intrinsic (contact)- slow
Extrinsic (tissue factor)- fast b/c tissue factor is already there to be released
What is the end result of the coagulation cascade?
Leads to activation of thrombin and the formation of
of
Prothrombin(II)→Thrombin(IIa) (cleaves fibrinogen)
Fibrinogen(I)→Fibrin(Ia)
What are the cofactors involved in the coagulation cascade? Why do we need cofactors?
Ca++ (binds to phospholipid)
Phospholipid (from platelet membranes)
Vit-K dep. factors: II, VII, IX, X, Protein S, C
Cofactors are needed for the enzymes to function (activated proenzyme)
What is the purpose of coagulation tests?
To test the ability to clot
Describe the partial thromboplastin time (PTT). What pathway is it associated with?
measures how long it takes for plasma to clot
screens for the activity of the proteins in the intrinsic pathway (factors XII, XI, IX, VIII, X, V, II, and fibrinogen)
negative-charged particles (e.g., ground glass) that activate factor XII (Hageman factor), phospholipids and calcium are added to plasma
What treatment is PTT used to monitor the efficacy of?
Heparin treatment
Heparin lengthens time to clot, we expect longer PTT
What is the purpose of prothrombin time (PT) test? What pathway is it involved with?
measures how long it takes for plasma to clot
screens for the activity of the proteins in the extrinsic pathway (factors VII, X, II, V, and fibrinogen
tissue factor, phospholipids, and calcium are added to plasma
What drug is PT used to guide treatment for?
Coumadin (vit. K antagonist)
Vit K dep factors involved in coagulation cascade
When we inhibit vit k we don’t have a cofactor
What other coagulation tests are used beside PT and PTT?
Bleeding time (platelets) (2-9 min)- prick finger and measure how long it takes for bleeding to stop
Platelet count (150,000-400,000/mm3)
Fibrinogen
Factor assays (find out what factor is deficient)
What is the fibrinolyitc system? What does it involve?
When we do not need to clot
Plasmin breaks down fibrin and interferes with its polymerization
Plasmin is generated by enzymatic catabolism of the inactive circulation precursor plasminogen
What is tissue plasminogen activator (tPA)?
Protease that cleaves plasminogen to Plasmin which breaks down fibrin and interferes with its polymerization in the fibrinolytic system.
What inhibits Plasmin?
α2-plasmin inhibitor is a plasma protein that binds and rapidly inhibits free plasmin
What marks the start of the extrinsic pathway?
Trauma
Tissue factor released
7 is activated
What is the end result of both the extrinsic and intrinsic pathways?
10 is activated
10a promote prothrombin to thrombin (5a is cofactor)
Thrombin cleaves fibrinogen to form fibrin
8a stabilizes clot
What marks the start of the intrinsic pathway?
Damaged surface
12 (hegamin factor) activates
How does TFPI inhibit the coagulation cascade?
In extrinsic it prevents the activation of 7
How does antithrombin inhibit the coagulation cascade?
Inhibits thrombin
Inhibits 10 from being activated which facilitates prothrombin to thrombin (2a)
Binds to heparin and thrombin
How does active protein C inhibit the coagulation cascade?
Inhibits 5 from activation (cofactor)
Inhibits 8 from activation (stabilizer)
What inhibits tPA?
PAI
