Hemodynamic disorders and normal and abnormal hemostasis Flashcards
What is maintained in normal fluid homeostasis?
- Vascular wall integrity
- Intravascular hydrostatic pressure
- Osmolarity
What is edema?
Where does it accumulate?
The accumulation of interstitial fluid in tissues
Subcutaneous tissues, body cavities (pleural cavity, pericardial cavity, peritoneal cavity)
What is anasarca?
Very severe generalized edema
What is the normal fluid balance?
2/3 intracellular
1/3 extracellular (interstitial)
with only 5% of extracellular fluid in vessels: blood plasma
What factors affect fluid balance?
Vascular hydrostatic pressure
Plasma colloid osmotic pressure (due to plasma proteins-albumin, globulin)
Lymphatic vessels pick up any residual
What causes edema?
- Increased hydrostatic pressure
- Decreased plasma osmotic pressure
- Lymphatic obstruction (lymphedema)
- Sodium (and water) retention
How does increased hydrostatic pressure occur?
Increased capillary pressure as a result of either venous obstruction or impaired venous return.
What are local examples of venous obstruction or impaired venous return? (leading to edema)
Deep vein thrombosis, mass lesion, lower extremity inactivity, cirrhosis
What is an example of a generalized venous obstruction or impaired venous return? (leading to edema)
Congestive heart failure.
Which also results in hypoperfusion of kidneys causing secondary hyperaldosteronism
What is another way that hydrostatic pressure can cause edema?
Arteriolar dilatation
as a result of Heat or Neurohumoral dysfunction (hypothalamic damage/malfunction)
How can edema occur from reduced plasma osmotic pressure?
Excessive loss of albumin leads to decreased intravascular volume and secondary hyperaldosteronism. (Albumin is the serum protein most responsible for maintaining colloid osmotic pressure)
What can cause albumin loss?
Nephrotic syndrome (protein-losing)
Protein-losing enteropathy (IBS, GI infections)
Malnutrition
Liver disease (reduced synth like cirrhosis)
How can lymphatic obstruction (lymphedema) cause edema?
Inflammatory
Neoplastic
Post-surgical/post radiation (removing lymphatic channels)
How does sodium (and water) retention occur?
Excessive salt intake w/ renal insufficiency
or
Acute reduction of renal function (like glomerulonephritis)
What causes subcutaneous edema?
Congestive heart failure and renal failure
What causes pulmonary edema?
Left ventricular failure
What causes edema of the brain?
Tumors cause focally
Viral infections cause diffusely
What is hyperemia?
An increase in blood volume within a tissue due to increased blood flow and arteriolar dilation.
An ACTIVE process.
Occurs at sites of inflammation
What is congestion?
An increase in blood volume within a tissue due to decreased/impaired outflow of venous blood.
A PASSIVE process
May occur systematically (liver and lung congestion due to heart failure) or locally (ex: obstruction of superior sagittal sinus of dura)
What are the two phases of clotting in normal hemostasis?
Primary and Secondary
What is important to the primary phase of clotting in normal hemostasis?
- Vasculature
- Blood flow
- Platelet count and function
- Extracellular matrix proteins
What is important to the secondary phase of clotting in normal hemostasis?
- Platelet plug
2. Coagulation factors
What are the important steps to primary hemostasis?
- Platelet adhesion
- Shape change
- Granule release
- Recruitment
- Aggregation
What are the important steps to secondary hemostasis?
- Tissue factor
- Phospholipid complex expression
- Thrombin activation
- Fibrin polymerization
What are important laboratory screenings for primary hemostasis?
- Platelet count
- Platelet function (PFA-100 and platelet aggregation studies)
- vWillebrand studies (vW antigen and vW activity)
What are important laboratory screenings for secondary hemostasis? And what specifically do they test?
- Prothrombin time [PT]- Test extrinsic and common pathways
- Activated partial thromboplastin time [aPTT]- Test intrinsic and common pathways
- Fibrinogen activity
What defects result in bleeding disorders?
- Vascular integrity
- Platelet count and/or function
- Von Willebrand factor deficiency or dysfunction
- Clotting factor deficiencies/inhibition (Hemophilia A (factor 8) or Hemophilia B (factor 9)/liver disease/anticoagulants)
What is scurvy?
Vitamin C deficiency leading to vessel fragility
What is thrombocytopenia?
Too few platelets
What is Glanzmann’s thrombasthenia?
An inherited defect within the platelet membrane
What does Vitamin K deficiency/warfarin cause?
Deficiency of factors 2, 7, 9, 10
What is disseminated intravascular coagulation (DIC)
Factor and Platelet consumption.
What is hemorrhage?
Extravasation of blood from vessels.
Accumulating within a space
What are common causes of hemorrhage?
Ruptured vessel (atherosclerosis, inflammation-vasculitis, aneurysm)
Peptic ulcer
Chronic congestion
Predisposition to hemorrhage with minimal trauma seen with decreased ability to clot
What is a hematoma?
Accumulation of blood within a tissue
What are petechial hemorrhages?
1-2 mm hemorrhages into skin, mucous membranes or serosal surfaces
Associated with low platelet counts(thrombocytopenia), platelet dysfunction, loss of vascular wall support, or local pressure.
What is purpura?
Greater than 3 mm hemorrhages.
Associated w same disorders as petechiae and w/ trauma, vaculitis, and vascular fragility
What are ecchymoses?
Greater than 1-2 cm subcutaneous hematomas.
Associated with trauma and exacerbated by the other conditions (assoc with purpura and petechiae)
What factors contribute to favor thrombosis?
Endothelial Injury
and
Abnormal Blood Flow
What factors contribute to inhibiting thrombosis?
Antithrombin III
Protein C and S
Tissue factor pathway inhibitor
PGI2
How do Protein C and S work?
Shut down Factor V and VIII
How does Antithrombin III work?
As thrombin is generated, antithrombin III shuts it down.
Hypercoagulability factors
Can be inherited or acquired.
Inherited: Factor 5 Leiden Protein C deficiency Protein S deficiency antithrombin III deficiency
Acquired:
Malignancy
Estrogens
Antiphospholipid antibody syndrome
What is Factor 5 Leiden
Most common inherited predisposition to thrombosis
Changes the cleavage site for protein C.
Activated Protein C resistance
Antiphospholipid antibodies?
Acquired autoantibodies against PL complexes
Assoc with arterial venous thromboses with high recurrence rates.
Inhibit clotting in vitro; promote clotting in vivo.
What are the 2 types of lab testing for antiphospholipid antibodies?
Lupus anticoagulant (prolongation of clotting based tests)
and
Anti-cardiolipin antibodies (immunoassays for anti-cardiolipin)
What is a thrombosis?
Formation of a blood clot within intact vessels
Where does a thrombus begin?
At a site of endothelial injury, or turbulence of flow, or site of blood stasis
What are the lines of zahn
Laminations apparent grossly or microscopically produced by alternating layers of platelets, fibrin, and RBCs
What are the three primary abnormalities that lead to thrombus formation?
Endothelial injury
Abnormal blood flow
Hypercoagulability
What is an embolus?
Detached intravascular mass carried by blood to site distant from origin.
Types of emboli
Thrombus (thromboembolism) Fat-rupture of vascular sinusoids/venules Air Amniotic fluid Tumor
Sources of thromboemboli?
Vessels (deep vein thrombosis occurring in leg veins)
Heart: atrial or ventricular walls or valve leaflets
Atherosclerotic plaque-abdominal aorta, carotid artery
Paradoxical embolism: travels through heart defect into systemic circulation (patent foramen ovale)
What is a pulmonary embolism?
Most common type of embolism
Usual source is DVT
Most are asymptomatic but serious consequences with saddle emboli (at bifurcation of pulmonary arteries) and multiple emboli.
What is infarction and what causes it?
Area of ischemic necrosis caused by occlusion of either the arterial supply or the venous drainage of a particular tissue.
What are the two types of infarcts and what causes them?
Red infarct: hemorrhagic-occurs in loose tissues, dual circulation tissues, when flow is re-established, venous occlusions
White infarct: anemic (no blood)- occurs in solid organs with end-arterial circulation. Like spleen or kidneys
DIC
Characterized by initial clotting (microangiopathy), resulting in organ ischemia, followed by bleeding tendencies.
Consumptive coagulopathy:
Widespread clotting leads to consumption of factors and platelets
Clotting factors consumed = bleeding
Platelets consumed = bleeding
Associated with severe illnesses
What is the difference between a hematoma and a hemorrhagic infarct?
In a hemorrhagic infarct, blood is intermixed with necrotic tissue; in hematoma blood is collected and form a solid mass
What is shock
Systemic hypoperfusion caused by
- reduced cardiac output or
- decrease in effective circulating blood volume
What are the 3 major types of shock
- Cardiogenic
- Hypovolemic
- Septic
What are other types of shock
Neurogenic shock and Anaphylactic shock
What are the stages of shock
- Nonprogressive phase
- Progressive phase
- Irreversible phase
What distinguishes hypovolemic and cardiogenic shock vs. septic shock and what is similar in their clinical presentation?
Cool, clammy, and cyanotic skin vs. warm and flushed (initially)
They are all hyptension, tachycardic, tachypnea
What causes septic shock most often?
Most often gram positive bacteria. Followed by gram negative bacteria and fungi.
