Hemodynamics
The study of how the red stuff moves around your people pipes. Normal blood flow is laminar, or aligned, moving, and non-turbulent.
Edema
The increased movement of fluid into the interstitial space. Clinical findings can include pitting, common in lower extremity edema, or pulmonary edema resulting in shortness of breath.
Examples
- Pleural effusion: Fluid in pleura of lungs (like from left heart failure)
- Pericardial effusion: Fluid in the pericardium around the heart
- Ascites: Fluid in the abdomen
- Anasarca: Diffuse edema
Pathology
Organs appear swollen, softer, and heavier. Clear/pink fluid can be found in tissue.
Hyperemia occurs as arterioles are dilating from inflammation or exercise, and result in increased blood volume. Congestion, by contrast, is always pathologic and results in increased blood flow from impaired outflow (like in congestive heart failure).
Hemostasis
Abnormal hemostasis occurs when the body is unable to stop blood loss or in thrombotic disorders, when there is over-clotting.
In normal hemostasis, megakaryocytes from the bone marrow creates a platelet plug (1* hemostasis). Secondarily, coagulation proteins (e.g., fibrin) are mobilized (2* hemostasis).
Platlet plug formation
Damage exposes subendothelium and Von Willebrand Factor (vWF). As platelets bind to vWF they change shape (helping clotting factors bind) and granules are released to trigger the coagulation cascade. The platelets then aggregate to form the plug.
Coagulation cascade
Both intrinsic and extrinsic coagulation pathways produce fibrin to consolidate the platelets. They happen at the same time and intersect at the activation of Factor X.
prothrombin → thrombin (via Factor X) → activates endothelial cells (adhesion and fibrinolysis) and leukocytes (inflammation)
fibrinogen → fibrin (via thrombin) → activation of factor XIII
Intrinsic pathway
Exposes Factor XII to a thrombogenic surface. Includes all factors except VII and XIII. It is tested in the lab with activated partial thromboplastin time (aPTT).
Extrinsic pathway
Requires addition of an exogenous trigger: Tissue Factor (TF). Includes factors I, II, VII, and X. It is tested in the lab with prothrombin time (PT).
Limiting factors
- Dilution can occur as coagulation factors are washed away by blood
- Decreased exposure to charged phospholipid platelet surfaces
- Antithrombotic properties of adjacent endothelium (fibrinolysis)
Fibrinolysis
Breaks down the clot to limit its size and restricts it to the site of injury. It also leads to eventual resorption. Alpha-2-plasmin inhibitor regulates the plasmin mediated breakdown of clotting.
- Plasminogen is activated by Tissue Plasminogen Activator (TPA), Urokinase, and Factor XII
- Plasminogen generates plasmin
- Plasmin breaks down fibrin (releasing measurable dimers to indicate thrombus formation)
Key modulators
| Thrombotic | Hemostasis Role | Function | |
|---|---|---|---|
| Von Willebrand Factor (vWF) | YES | Primary | Produced by endothelium, enhances platelet adhesion |
| Pro-coagulation tissue factor (TF) | YES | Secondary | Stimulated by endotoxins or cytokines, activates extrinsic coagulation cascade |
| Plasminogen activator inhibitors | YES | Fibrinolysis | Produced by endothelium, suppresses fibrinolysis |
| Intact endothelium | NO | Primary | Prevents subendothelium from contacting platelets |
| Prostacyclin | NO | Primary | Produced by endothelium, vasodilator inhibitor of platelet aggregation |
| Nitric oxide | NO | Primary | Produced by endothelium, inhibits platelet aggregation |
| Adenosine diphosphatase (ADPase) | NO | Primary | Expressed on endothelial cells, degrades ADP and inhibits platelet aggregation |
| Heparin-like molecules | NO | Secondary | Cofactors of antithrombin III (inactivates thrombin) |
| Thrombomodulin | NO | Secondary | Binds thrombin and cleaves factors Va/VIIa |
| Tissue Factor Pathway Inhibitor (TFPI) | NO | Secondary | Found on surface of endothelium, inhibits TF |
| Tissue-type plasminogen activator (t-PA) | NO | Fibrinolysis | Produced by endothelium, clears fibrin |
Hemorrhage
Blood going on an independent streak.
Vocab
Hematomas: Accumulation of blood in a tissue
Petechiae: Small (1-2mm) hemorrhages from capillary damage caused by hypoxia or abnormalities in platelets.
Purpura: Bigger hemorrhages on skin secondary to trauma, inflammation, or vascular fragility.
Ecchymoses: Larger bruises/hemorrhages of deeper subcutaneous tissue associated with trauma
Hemothorax: Accumulation of blood in pleura
Hemopericardium: Accumulation of blood in pericardia (often secondary to aortic rupture)
Hemarthroses: Accumulation of blood in joint space
Thrombocytopenia is when platelets are low in general
Thrombosis
Formation of a thrombus (abnormal aggregation of platelets, fibrin, and other trapped elements).
Virchow's Triad
What leads to thrombus formation.
- Endothelial injury
- Abnormal flow
- Hypercoagulability
A note on 2: Clots from turbulent flow come from the the cellular layer being in contact with the epithelium. This prevents the dilution of clotting factors and inflow of inhibitors. Stopped flow will also result in this.
Arterial thrombosis
Occlusive, gray-white. Occurs when there is already stenosis (narrowing) of the vessel.
Venous thrombosis
Reddish, mostly red blood cells. Can come from immobility leading to static blood. A Deep Vein Thrombosis (DVT) in the leg is common, and may travel, becoming an embolism.
Mural thrombosis
Forms in the wall of the heart. Usually occurs in hypocontractility (after a heart attack, for example) or endocardial damage leading to turbulence. These thrombi can also travel, becoming an embolism.
Embolism
Material masses moving around the body, potentially getting stuck somewhere.
Thromboembolism
Most common form.
Pulmonary embolisms are pieces of venous thrombus (usually from the femoral vein) which deposits in branches of the pulmonary artery.
Systemic embolism arise from mural thrombi in the heart and can result in an arterial embolism in the brain (stroke), intestine, lower extremity, or kidney.
Fat embolism
After significant fracture or burn, portions of the bone marrow are released into the blood. Because fat is an irritant, it will trigger coagulation in the endothelium. This is usually asymptomatic, but severe forms can lead to respiratory failure, mental confusion, disseminated intravascular coagulation (DIC), anemia, and thrombocytopenia.
Air embolism
Gas bubbles in the circulation which can obstruct vascular flow, This can happen with some surgeries, upon exposure to increased atmospheric pressure, such as in the case of getting the bends from scuba.
Amniotic fluid embolism
Rare complication of pregnancy where amniotic fluid enters the maternal circulation via tears in maternal veins. Amniotic fluid has a lot of pro-coagulant factors and is obstructive. Can cause mental confusion, agitation, and shortness of breath. Often fatal.
Infarction
Ischemic necrosis caused by occlusion of arterial supply.
White infarction
In an end artery of an organ (end point of blood)
Red infarction
Where there is bleeding into he infarct. This can take the form of previous congestion, an issue with outflow from an organ, or re-perfusion.
Myocardial infarction
Ischemic injury of heart muscle in a perfusion zone of the occluded artery.
Cerebral infarction
Stroke/CVA. An ischemic or hemorrhagic parenchymal injury as a result of arterial occlusion (atherosclerosis) or the result of an embolism.
Bowel infarction
Ischemic bowel, often fatal in the elderly.