Hemodynamic Disorders Flashcards
Forces pushing fluid out of a vessel
hydrostatic pressure
Osmotic force keeping fluid in a vessel
Oncotic pressure
What is normally more than the other?
Forces keeping fluid in vessels or forces pushing/allowing fluid out?
Forces pushing/allowing fluid out is slightly greater
Excess interstitial fluid
Edema
Excess fluid in a cavity
Effusion
Intra-abdominal effusion
Ascites
3 reasons for excess fluid
Increased hydrostatic pressure
Decreased oncotic pressure
Increased vascular permeability
3 reasons for increased hydrostatic pressure
Decreased venous return (may be local or systemic)
Increased plasma volume (kidney failure or increased Na retention)
Decreased lymphatic drainage (tumor, filariasis, scar tissue)
2 reasons for decreased oncotic pressure
Decreased protein production (liver failure or malnutrition)
Increased protein loss (kidney failure or diarrheal illness)
Fluid high in protein and cellularity
Seen in situations with high vascular permeability (inflammation, endothelial damage)
Exudate
Fluid low in protein and cellularity
Seen in situations with high hydrostatic pressure or low colloid pressure (heart or liver failure)
Transudate
Does high or low hydrostatic pressure lead to transudate?
High
Disorder of perfusion involving increased intravascular blood due to increased inflow (inflammation)
Hyperemia
Disorder of perfusion involving increased intravascular blood due to decreased outflow (heart failure)
May cause hepatomegaly
Congestion
Disorder of perfusion involving blood leaving vascular space
Trauma, vascular disease, coagulopathy
Hemorrhage
What is hyperemia (increased intravascular blood) due to?
Increased inflow
What is congestion (increased intravascular blood) due to?
Decreased outflow
Condition that makes someone vulnerable to bleeding with small injury
Can cause hemorrhages
Can involve platelets or coagulation proteins
Coagulopathy
Pinpoint hemorrhage in skin or cornea
Due to microvascular rupture
Petechiae
Diffuse superficial hemorrhages in skin
Often a confluence; often seen in small vessel disorders
Purpura
Larger collection of blood in superficial skin
Ecchymosis
Progression of bruise colors due to RBC degradation:
First to appear
Hemoglobin (red)
Progression of bruise colors due to RBC degradation:
Second to appear
Deoxyhemoglobin (blue-red)
Progression of bruise colors due to RBC degradation:
Third to appear
Biliverdin (yellow-green)
Progression of bruise colors due to RBC degradation:
Fourth to appear
Hemosiderin (yellow-brown)
Collection of blood in soft tissue of parenchymal organ
Hematoma
Collection of blood in anatomic space
Hemorrhagic effusion
Normal process to stop hemorrhage
Has three main contributing systems (vascular, platelets, coagulation)
Hemostasis
3 main contributing systems to hemostasis
Vascular (vascular activities slow or prevent hemorrhage)
Platelets (contribute to clot and help activate coagulation)
Coagulation (produces a fibrin meshwork)
Lining cell of blood vessels
Endothelium
Endothelium releases this which is a vasodilator that inhibits platelet aggregation
Prostacyclin (PG-I2)
Endothelium releases this which is a vasodilator
NO
Endothelium produces this which degrades platelet ADP
ADPase
Small disk shaped cytoplasmic buds from bone marrow megakaryocytes
Platelet
Platelet are small disk shaped cytoplasmic buds from these
Bone marrow megakaryocytes
Thrombocyte is another name for these
Platelets
Component with these procoagulant activities:
Provide surface phospholipid for coagulation factors
Provide ADP to activate others
Aggregate to form initial plug
Platelets
Platelets provide surface ______ for coagulation factors
Phospholipid
Coagulation system where:
Vascular injury induces vasoconstriction
Endothelium is activated to secrete vWF
Platelets adhere, activate, aggregate
Primary hemostasis
Coagulation system where:
Soluble coagulation factors –> fibrin
Fibrin clot forms to enmesh platelet aggregate
Secondary hemostasis
Coagulation system where:
Counter-regulatory measures keep it local
Tertiary hemostasis
3 main steps of hemostasis
- Vasoconstriction
- Platelet plug
- Coagulation cascade
Damaged endothelium releases this, which leads to vasoconstriction
Transient effect
Promotes smooth muscle constriction
Vessel caliber decreases
Endothelin
Endothelin is released by this
Damaged endothelium
Endothelin has this effect
Vasoconstriction
Platelets adherence to exposed collagen (ECM) is mediated by this interaction
Glycoprotein Ib (platelet receptor) binding to von Willebrand factor (which is produced by endothelium and platelets, and binds to exposed collagen)
This is produced by endothelium and platelets
Binds to exposed collagen
Is bound by glycoprotein 1b on platelets
von Willebrand factor (vWF)
What is the role of von Willebrand factor (vWF)?
Mediates platelets adherence to exposed collagen (ECM)
Is produced by endothelium and platelets
Binds to exposed collagen
Is bound by glycoprotein 1b on platelets
Platelet receptor that binds to vWF during platelets adherence to exposed collagen
Glycoprotein Ib
This binds to platelet receptor, changing platelet shape to have “sticky ends” (starfish shape)
Thrombin (or ADP or serotonin)
After changing shape due to thrombin, platelet sticky ends have high density of this
Glycoprotein 2b/3a
4 steps of platelet activation during primary hemostasis
Platelet change shape
Glycoprotein 2b/3a concentrates on tips of filopodia
ADP/serotonin released (activate nearby platelets)
Fibrinogen released
Interaction that causes platelets to aggregate
Glycoprotein 2b/3a binds fibrinogen polymer to form connecting bridge between platelets
Role of glycoprotein 2b/3a
Binds fibrinogen polymer to form connecting bridge between platelets
Results in platelet aggregation
Role of glycoprotein 1b
Binds vWF –> Platelet adherence to ECM
Formation of fibrin clot involves a cascade of these enzymes
Serine proteases
Intrinsic pathway of fibrin clot formation starts with this
Begins fibrinolysis
Factor XII exposure to negatively charged surface
Factor XII exposure to this starts the intrinsic pathway of fibrin clot formation
Negatively charged surface
Factor XII activates this
XI –> XIa
XIa activates this
IX –> IXa
(X is skipped)
IXa activates this
VIII –> VIIIa
Extrinsic pathway of fibrin clot formation starts with this
Factor VII exposure to Tissue Factor
Factor VII exposure to this starts the extrinsic pathway of fibrin clot formation
Tissue Factor
Tissue Factor activates this
Factor VII –> VIIa
Convergence of the intrinsic and extrinsic pathways of fibrin clot formation
VIIIa and VIIa can both activates X to Xa
Xa activates this
II (Prothrombin) –> IIa (Thrombin)
Factor II aka
Prothrombin
Factor IIa aka
Thrombin
Prothrombin is this factor
Factor II
Thrombin is this factor
Factor IIa
Factor II (thrombin) activates these
Platelets
IIa activates this
Factor I (fibrinogen) –> Ia (fibrin)
Fibrinogen is this factor
Factor I
Fibrin monomer is this factor
Factor Ia
Factor I aka
Fibrinogen
Factor Ia aka
Fibrin monomer
Acute phase reactant that is secreted by pIt and endothelium
Produced as the end of the serine protease cascade during fibrin clot formation
Factor I = fibrin
These form polymers to enmesh platelets
Are cross-linked via Factor XIIIa
Fibrin
Fibrin is cross-linked to enmesh platelets via this
Factor XIIIa
Regulatory protein that inhibits Factor Va
Protein C
Protein C inhibits this
Va
Cofactor for Factor Xa
together they cleave prothrombin (factor II)
Va
Va is a cofactor for this
Factor Xa
together they cleave prothrombin (factor II)
Protein C has this cofactor
Protein S
Together they inactivate Factor Va
Protein S is a cofactor for this
Protein C
Together they inactivate Factor Va
Expressed by intact endothelium
Binds thrombin (IIa), together they activate Protein C (which inactivates V)
Thrombomodulin
Thrombomodulin is expressed by this
Intact endothelium
Thrombomodulin binds this, and together they activate Protein C
Thrombin (factor IIa)
Thrombomodulin binds Thrombin (IIa), and together they activate this
Protein C
Protein C receptor is expressed by this
Intact endothelium
Expressed by intact endothelium
Inhibits thrombin, Factors 9-12
Antithrombin III
Antithrombin III is expressed by this
Intact endothelium
Antithrombin III inhibits these
Thrombin, Factors 9-12
Factor XIIa cleaves
Plasminogen to plasmin
This cleaves plasminogen to plasmin
Factor XIIa
This is expressed by endothelium into clot and activates plasminogen to plasmin
Tissue plasminogen activator (tPA)
This cleaves fibrin polymers back to monomers
Clot dissolves
Plasmin
Mucosal bleeding, skin bleeding, severe thrombocytopenia are defects in this
Primary hemostasis
Soft tissue bleeds (hematomas) and hemarthroses (blood in joint space) are defects in this
Secondary hemostasis
Thrombosis and hypercoagulability are defect in this
Tertiary hemostasis
Intravascular (including intra-cardiac) blood clot formation
Thrombosis
Term for 3 factors that promote thrombus formation
Virchow’s triad
Define Virchow’s triad
3 factors that promote thrombus formation
(Endothelial injury, Blood stasis or turbulence, Hypercoagulability)
Activated endothelium (due to injury) down regulates these 3 things to promote a procoagulant state
Thrombomodulin
Protein C receptor
Tissue plasminogen activator (tPA)
This is a major factor in arterial thrombosis
Endothelial injury
Endothelial injury is a major factor in _______ thrombosis
Arterial
Stasis is a major factor in _______ thrombosis
Venous
low flow state and stasis allows factor accumulation
Turbulence is a major factor in _______ thrombosis
Arterial or venous
Hypercoagulability is a major factor in _______ thrombosis
Venous
Example of hypercoagulability involving decreased function of anticoagulant force
Factor V Leiden (genetic mutation)
Example of hypercoagulability involving increased function of pro-coagulant force
Prothrombin G20210A (genetic condition)
4 clinical states that can produce Virchow’s Triad and clotting
Estrogenic states (hypercoagulability)
Pregnancy (hypercoagulability)
Atrial fibrillation (turbulent blood flow)
Coronary atherosclerosis (turbulent blood flow)
Thrombi that occur in cardiac chambers, usually a result of turbulence of stasis
Mural thrombi
Thrombi frequently associated with atherosclerotic plaque
Often occlusive
Arterial thrombi
Thrombi frequently associated with stasis and hypercoagulable states
“Always” occlusive
Form lines of Zahn
Venous thrombi
Alternating zones of cell-rich and platelet/fibrin rich areas
Form in states of flowing blood
Form in venous thrombi
Lines of Zahn
This type of plaque predisposes to an arterial thrombus (produces turbulent blood flow due to plaque distorting shape of blood vessel)
Atherosclerotic
Thrombus propagation:
Retrograde growth from attachment site
Arterial
Thrombus propagation:
Anterograde growth from attachment site
Venous
When fragment thrombus fragment dislodges and travels downstream
Embolization
4 stages of the thrombus life cycle
Propagation
Embolization
Dissolution due to fibrinolytic system
Organization
Thrombus obstruction involving congestion, edema, and pain due to inflammation (thrombophlebitis)
Venous thrombus obstruction
Thrombus obstruction involving ischemia and possible death or organ receiving blood
Arterial thrombus obstruction
What is thrombophlebitis?
Venous thrombus obstruction
Loose intravascular material carried by blood stream
Embolism
Detached thrombus; most common form of embolism
Thromboembolism
Where do venous thromboembolism end up?
Lung
(Right atrium –> right ventricle –> lung)
= Pulmonary embolism
Pulmonary embolism that begins in deep veins of leg
Deep vein thrombosis
Result of a large clot that obstructs pulmonary vasculature
Sudden death
Result of a smaller clot that obstructs pulmonary vasculature
Asymptomatic or chest pain
Infarction is uncommon
Type of embolism usually due to long bone fractures
Source = bone marrow
Multiple small emboli lodge in lung and/or systemic circulation (which could go to brain)
Produces endothelial injury and platelet aggregation (leading to low platelet counts)
Fat embolism
Source of fat for fat embolism
Fat embolism
This can occur during a fat embolism, causing respiratory distress, dyspnea, or mental status changes
Multiple small emboli lodge in lung and/or systemic circulation (which could go to the brain)
Type of embolism that involves platelet aggregation, leading to low platelet counts
Results in thrombocytopenia
Fat embolism
This is often an earlier sign of a fat embolism
Platelet aggregation, leading to low platelet counts (thrombocytopenia)
Introduction of gas into vasculature
Mechanisms: vessels open to air + negative pressure
Iatrogenic causes (neurosurgery, obstetrics, thoracic), or from trauma (chest wall especially) or decompression sickness
Air embolism
Obstetric complication where uterine vasculature opens during placental separation
Amniotic fluid enters circulation and contains baby’s epithelial cells/debris
Lodged in narrowed points of circulation
Foreign material produces intravascular coagulation of mother
Amniotic fluid embolism
Amniotic fluid embolism causes damage when amniotic fluid enters circulation, gets lodged in narrowed points of circulation or the foreign material produces this
Intravascular coagulation of mother
Tissue necrosis due to ischemia
Most due to arterial atherosclerosis and/or thromboemboli
Infarct
This type of blood supply is more resistant to infarcts
Dual blood supply (e.g. lungs)
2 examples of tissues that have short duration ischemia –> infarct
CNS and myocardium
Tissue type that survives many hours of ischemia
Fibrous tissue
Infarcts are usually this shape
Wedge shaped
Color of infarct if end-arterial organ (e.g. spleen, bone)
Pale
Color of infarct if organ with dual blood supply (e.g. lung, liver)
Hemorrhagic
Typical type of necrosis of infarct
Coagulative necrosis
Infarct is hemorrhagic if due to this
Venous obstruction
This type of margins often occur in infarcts
Hyperemic
Usual result of this type of infarct is congestion and edema
Less common
Collaterals allow tissue survival
Venous infarct
Infarct occurs if enough hemorrhage occurs to obstruct arterial flow
2 mechanisms of ischemic injury
Lack of ATP
Generation of ROS/free radicals (mitochondrial damage or lack of O2)
Increased tissue damage and inflammation due to blood flow restoration
Should provide O2 to reversibly damaged cells and allow survival, but sometimes this causes increased cell death
Reperfusion injury
3 mechanisms of reperfusion injury cell death
Damaged mitochondria (increased ROS, release of cytochrome C)
Blood flow brings WBCs to sites attracted by DAMPs –> increase ROS
Blood flow brings Ca2+ to damaged cells –> pro-death pathways
What is contraction band necrosis?
Increased Ca2+ causes contraction of actin-myosin
Circulatory failure with decreased perfusion and global cellular hypoxia
Shock
These are the 3 main mechanisms of this:
Inadequate pumping
Too little intravascular volume
Vasodilation
Shock
Cardiogenic shock
Hypovolemic shock
Septic/anaphylactic/neurogenic shock
Type of shock caused by vasodilation involving bacterial infection
Septic shock
3 phases of shock
Compensated phase
Decompensated phase
Irreversible phase
Low renal blood flow results in release of this during shock
Renin
Renin release due to low renal blood flow has these two effects
Angiotensin release –> vasoconstrictoin
Aldosterone release –> kidneys increase sodium and water retention
Low hypothalamic blood flow results in release of this
ADH
These are symptoms of this:
Low pressure, fast pulse
Pale (parenchymal/skin vasoconstriction)
Renal vasoconstriction and renal water retention
Compensated phase of shock
Phase of shock involving organ hypoperfusion
Goal is to maintain cardiac output and blood pressure
Compensated phase
These decrease parasympathetic stimulation during the compensated phase of shock, leading to increased cardiac pumping
Baroreceptors
Baroreceptors lead to this characterization of the compensated phase of shock
Increased cardiac phase (fast pulse)
Phase of shock involving cerebral, renal, liver, cardiac, and muscle hypoperfusion
Cellular metabolism shifts to anaerobic metabolism (increased lactic acid)
Decompensated phase of shock
Why is there increased creatinine during the decompensated phase of shock?
Renal hypoperfusion
Why is there increased AST/ALT during the decompensated phase of shock?
Liver hypoperfusion
Why is there increased lactic acid during the decompensated phase of shock?
Cellular metabolism shifts to anaerobic metabolism
Phase of shock where organ damage is too extensive to reverse
Progresses to multiorgan system failure
Cardiac ischemia –> decreased cardiac output
Intestinal ischemia –> bacteremia –> sepsis
Irreversible phase
Especially severe form of shock due to systemic infection
Septic shock
Type of microorganism that most prominently causes septic shock
Gram positive > gram negative > fungal infection
During septic shock, there is widespread ______ activation
Endothelial
These are factors of this:
Microbial products activate innate immune system
Generalized cytokine release
Widespread endothelial activation (NO synthase, anticoagulant factors decreased)
Complement activation
Septic shock
During septic shock, these factors are decreased
Anticoagulant factors decreased, promoting a procoagulant state
During septic shock, a procoagulant state is promoted by these 3 things
Decreased thrombomodulin
Decreased protein C
Tissue Factor released