Accumulation of interstitial fluid in tissues, including subcutaneous tissues and body cavities
What is anasarca?
Very severe generalized edema
What is the most common cause of lymphatic obstruction (lymphadema)?
Post-surgical or post-radiation therapy scarring/removal of lymph channels.
Name 4 general pathopysiologic causes of edema
- Increased capillary hydrostatic pressure due to arterial dilation or impaired venous return
- Reduced plasma osmotic pressure due, possible due to excessive loss of albumin (nephrotic syndrom, protein-losing enteropathy, malnutrition, liver disease/cirrhosis)
- Lymphatic obstruction (lymphedema) due to inflammatory, neoplastic, or iatrogenic (surgery, radiation) processes
- Sodium (and water) retention due to excessive salt intake or acute reduction in renal function
Define hyperemia. Where does it occur?
Increase in blood volume within a tissue due to increased blood flow and arteriolar dilation. Hyperemia is an active process that commonly occurs at the site of inflammation or in exercising skeletal muscles.
Define congestion. Where does it occur?
Increase is blood volume in a tissue due to impaired/decreased outflow of venous blood (passive process).
Systemic: liver and lung congestion due to heart failure
Local: obstruction of superior saggital sinus
List the general steps in primary hemostasis (5)
- Platelet adhesion
- Platelet shape change
- Platelet granule release
- Aggregation and formation of hemostatic plug
Name the general steps in secondary hemostasis (4)
- Tissue factor release
- Phosphlipid complex expression
- Thrombin activation
- Fibrin polymerization
What does Prothrombin time (PT) measure?
Extrinsic pathway + common pathway
What does Activated Partial Thromboplastic time (aPTT) measure?
Intrinsic pathay + common pathway
Hemophilia A features a defect in what clotting factor? Hemophilia B?
A: Factor VIII
B: Factor IX
Which clotting factors are dependent on vitamin K?
Factors 2, 7, 9, 10
Name the hemodynamic disease matching each of the following bleeding disorder mechanisms or descriptions:
- Factor 9 deficiency
- General factor deficiencies or dysfunction
- Inherited defect in platelets causing a deficiency of gpIIb/IIIa expression on platelet membranes
- Too few platelets
- Vitamin C deficiency leading to vessel fragility (collagen synthesis issue)
- von Willebrand factor deficiency or dysfunction
- Platelet and clotting factor consumption due to systemic clotting followed by systemic bleeding
- Deficiency of factors 2, 7, 9, 10
- Factor 8 deficiency
- Hemophilia B
- Liver disease
- Glanzmann's thrombasthenia
- von Willbrand disease
- Disseminated Intravascular Coagulation (DIC)
- Vitamin K deficiency (or Warfarin therapy)
- Hemophilia A
What is hemorrhagic diathesis?
A predisposition to hemorrhage, even with minimal trauma
Accumulation of blood within a tissue
Define and describe: petechial hemorrhage
1-2mm hemorrhage, usually into skin, mucous membranes, or serosal surfaces. Petechiae can be associated with low platelet counts (thrombocytopenia), platelet dysfunction, loss of vascular wall support, or local pressure.
Define and describe: purpura
>3mm hemorrhage, usually into skin, mucous membranes, or serosal surfaces. Purpura can be associated with low platelet counts (thrombocytopenia), platelet dysfunction, loss of vascular wall support, or local pressure.
Define and describe: ecchymosis
>1-2cm subcutaneous hematoma. Known more commonly as a 'bruise'. Associated with trauma.
Name and describe 4 mechanisms for that inhibit thrombosis
- Heparin-like molecules are bound by Antithrombin III (atIII). The atIII-heparin complex binds thrombin, inactivating it. The atIII-heparin complex also inactivates factors 9a and 10a.
- Tissue factor pathway inhibitors expressed on the surface of vascular endothelial cells inactivates 7a-TF complexes
- Thrombin activates thrombin receptors expressed on vascular endothelial cells, increasing endothelial cell expression/realease of t-PA, which activates the fibrinolytic cascade. Endothelial cells also increase expression of PGI2, NO, and adenosinediphosphatase, all of which inhibit platelet aggregation.
- Thrombin binds thrombomodulin, a receptor expressed on the surface of vascular endothelial cells. The thrombin-thrombomodulin complex activates protein C, which (via protein S), deactivates factors 5a and 8a.
What is Factor 5 Leiden?
- Most common inherited predisposition to thrombosis
- Via single point mutation in the cleavage site on factor V for protein C
- Activated protein C, with protein S, degrades factors 5a and 8a, shutting down the normal clotting cascade.
- Severity depends on number of defective alleles inherited (more alleles increases severity up to 50x risk for thrombosis)
What are antiphospholipid antibodies? How are they tested for?
- Acquired autoantibodies against phospholipid complexes associated with thrombosis
- Lab testing: lupus anticoagulant and anti-cardiolipid antibodies
- Inhibit clotting in vitro (longer clotting time test); promote clotting in vivo (increased risk of thrombosis)
What are Lines of Zahn?
Laminations of alternating layers of platelets, fibrin, and RBCs characteristic of thrombosis.
What is Virchow's Triad in Thrombosis?
Three primary abnormalities that lead to thrombus formation:
- Endothelial injury
- Abnormal blood flow
What is stasis?
Slow of sluggish flow of blood. Increases risk of thrombosis due to decreased washout of clotting factors and decreased inflow of clotting factor inhibitors.
What is a cardiac mural thrombus?
A thrombus attached to the heart wall, usually at or near the site of MI. Decreased contraction contributes to abnormal flow near this site, increasing the risk of thrombus formation.
Name 5 types/sources of emboli
- Thrombus (thromboembolism)
- Fat, often due to long bone fractures, soft tissue trauma, and burns
- Air - obstetric procedures, chest wall injuries, decompression sickness
- Amniotic fluid - delivery
What is name for a thrombotic mass attached to a heart valve?
What is a paradoxical embolism?
an embolism that travels through a heart defect (such as a patent foramen ovale), producing an obstruction on the arterial side of systemic circulation
What is the most common thrombotic source of pulmonary embolism (PE)?
Deep vein thrombosis (DVT)
What is a saddle embolus?
An embolus lodged at a bifurcation of the pulmonary arteries.
What is a red infarct? Where is it more likely to occur?
A hemorrhagic infart, usually occurrin in loose tissues or tissues with secondary circulation. May also occur in cases where flow is re-established post-infarct, or with venous occlusions.
What is a white infarct? Where are they most likely to occur?
Anemic infarct (no blood). Occur primarily in solid organs with end-arterial circulation. Examples include kidneys and spleen.
What is the difference between a hemorrhagic infarct and a hematoma?
Hematoma: blood is collected to form a solid mass
Hemorrhagic infarct: Blood is intermixed with necrotic tissue
Define and describe the mechanism behind Disseminated Intravascular Coagulation (DIC)
- Initial widespread clotting resulting in organ ischemia, followed by bleeding tendencies
- Associated with severe illness (burns, sepsis, trauma, cancer, etc)
- Initial clotting leads to comsumptive coagulopathy. The significant decrease in available clotting factors and platelets leads to bleeding tendency.
Systemic hypoperfusion caused by:
- Reduced cardiac output (MI, PE, arrhythmia, etc)
- Decrease in effective circulating blood volume (hemorrhage, hypotension, etc)
Name and describe 3 major types of shock
- Cardiogenic - failure of myocardial pump
- Hypovolemic - inadequate blood or plasma volume
- Septic - peripheral vasodilation and pooling of blood seconary to overwhelming microbial infection.
What is neurogenic shock?
Interruption of sympathetic vasomotor output due to spinal cord injury. Results in arteriolar/venous dilation and decrease cardiac output.
Define anaphylactic shock
IgE-mediated hypersensitivity response, leading to systemic vasodilation, leading to shock
Name and describe the 3 major phases of shock
- Nonprogressive: tachycardia, peripheral vasoconstriction, renal fluid conservation. Perfusion of organs maintained.
- Progressive: tissue hypoxia and lactic acidosis due to widespread tissue hypoperfusion
- Irreversible: cellular and organ injury preventing survival (ischemia and massive lactic acidosis)
What type(s) of shock present with the following?
- Hypotension, tachycardia, tachypnea
- Cool, clammy, cyanotic skin
Hypovolemic or Cardiogenic shock
What type(s) of shock present with the following?
Hypotension, tachycardia, tachypnea
Warm and flushed skin (initially)
(Initial warm/flushed skin is due to peripheral vasodilation)
Characterize the infection pattern in septic shock
Most often gram-positive bacteria, followed by gram-negative bacteria and fungi