Hemostasis and Edema Overview

Overview

• Hemostasis is the process of blood clotting.
• Inadequate hemostasis can lead to hemorrhage, extravasation of fluid into tissues, and compromise regional tissue perfusion.
• Massive and rapid hemorrhage may lead to hypotension, shock, and death.

Thrombosis & Embolism

• Thrombosis is inappropriate clotting within a blood vessel.
• Embolism is a clot that travels from its original position to a different location in the vascular system.
• Infarction is ischemic cell death due to obstruction of blood vessels by thrombosis or embolism.

Edema & Effusions

• Edema is fluid accumulation in the interstitial spaces.
• Lymphatic vessels remove excess fluid, but if the rate of fluid movement exceeds lymphatic drainage, edema develops.
• Edema fluids and effusions can be inflammatory (exudates) or non-inflammatory (transudates).

Categories of Edema

• Increased hydrostatic pressure is a major cause of edema, particularly in cases of impaired venous return, such as congestive heart failure, venous obstruction, and prolonged dependency.
• Reduced plasma osmotic pressure (hypoproteinemia) due to conditions like nephrotic syndrome, liver cirrhosis, malnutrition, and protein-losing gastroenteropathy can also cause edema.
• Lymphatic obstruction due to inflammation, neoplasia, post-surgical or post-irradiation complications can contribute to edema.
• Sodium retention due to excessive intake, renal hypoperfusion, and increased tubular reabsorption of sodium can lead to edema.

Morphological Features of Edema

• Gross appearance of edema includes swelling of the affected body part.
• Subcutaneous edema is commonly found in tissues with high hydrostatic pressure, often appearing in dependent areas due to gravity.
• Pitting edema is characterized by a depression that remains after finger pressure is released.
• Periorbital edema often indicates severe renal dysfunction.
• Effusions (fluid accumulation in body cavities) are common in a wide range of clinical settings.

Clinical Features of Edema

• Subcutaneous edema is important because it may signal underlying cardiac or renal disease.
• Peritoneal effusions (ascites), often caused by portal hypertension, are characterized by the accumulation of fluid in the peritoneal cavity.

Thrombi

• Antemortem (pre-death) clots, both venous and arterial, can be differentiated from postmortem clots based on appearance, texture, attachment to vessel wall, color, and blood flow influence.
• Antemortem clots are firmer, more homogeneous, and display lines of Zahn (alternating layers of platelets and fibrin)
• Postmortem clots are softer and gelatinous.
• Antemortem clots are pathologic as they can lead to embolism or occlusion, while postmortem clots are a natural postmortem change.

Vegetations

• Vegetations are thrombi on heart valves, which can either be infected (infective endocarditis) or sterile (nonbacterial thrombotic endocarditis or Libman-Sacks endocarditis).

Fate of Thrombi

• Thrombi can dissolve, organize, or become incorporated into the vessel wall.

Disseminated Intravascular Coagulation (DIC)

• DIC is widespread thrombosis within the microcirculation.
• It can occur suddenly or insidiously, often during endovascular procedures, interventions, or mechanical ventilation.

Air Embolism

• Air embolism is the presence of air bubbles in the bloodstream.
• The volume of air necessary to produce a clinical effect is greater than 100 mL.
• Fatal effects are associated with volumes between 300-500mL introduced at a rate of 100 mL/second.

Fat Embolism

• Fat embolism is the presence of fat globules in the bloodstream.
• It often occurs after trauma involving bone fractures.
• Fat embolism syndrome is characterized by pulmonary insufficiency, neurologic symptoms, anemia, thrombocytopenia, and can be fatal in 5-15% of cases.

Decompression Sickness

• Decompression sickness is a form of gas embolism caused by rapid changes in atmospheric pressure.
• It is common among divers who ascend too quickly from a deep dive.

Systemic Inflammatory Response Syndrome (SIRS)

• SIRS is a sepsis-like condition associated with systemic inflammation.
• It can be triggered by microbial or non-microbial insults, such as burns, trauma, and pancreatitis.
• The pathognomonic feature of SIRS is the massive outpouring of inflammatory mediators from innate and adaptive immune cells.

Activation of the Complement Cascade

• The complement cascade can be directly activated by microbial components or indirectly by the proteolytic activity of plasmin.

• Activation of the complement cascade results in the production of anaphylotoxins (C3b), chemotactic fragments (C5a), and opsonins (C3b), contributing to the pro-inflammatory state.

• Activation of the coagulation cascade is another consequence of complement activation.### Cytokine Release Syndrome

• Triggered by microbial components.

• Occurs in cancer patients undergoing CAR-T therapy.

• Can be activated directly through Factor XII or indirectly through altered endothelial function.

• Direct Activation: Factor XII activation can lead to widespread Thrombin activation which further augments inflammation by triggering protease-activated receptors on inflammatory cells.

• Indirect Activation: Altered endothelial function can contribute to inflammation.

Systemic Inflammatory Response Syndrome (SIRS)

• Leads to tissue hypoperfusion, cellular hypoxia, metabolic derangements, and organ dysfunction.
• Can result in organ failure and death if severe and persistent.

Hyperinflammatory State

• Initiated by sepsis.
• Triggers counter-regulatory immunosuppressive mechanisms involving both innate and adaptive immune cells.
• Septic patients may alternate between hyperinflammatory and immunosuppressed states.

Proposed Mechanisms of Immune Suppression

• Shift from pro-inflammatory (Th1) to anti-inflammatory (Th2) cytokines
• Production of anti-inflammatory mediators such as soluble TNF receptor, IL-1 receptor antagonist, and IL-10.
• Lymphocyte apoptosis.

Less Common Categories of Shock

• Neurogenic Shock: Arises in the context of a spinal cord injury.
• Anaphylactic Shock: Triggered by an IgE-mediated hypersensitivity reaction.
• Common Feature: Acute vasodilation leading to hypotension and tissue hypoperfusion in both forms of shock.

Pathogenesis of Septic Shock

• Most frequently caused by bacteria.

This quiz covers the essential concepts of hemostasis, thrombosis, embolism, and edema. It explores how inadequate hemostasis can lead to severe complications, along with the different types of edema and their causes. Test your understanding of these critical physiological processes.