Clase 36 Fisiología Sanguínea - Hemostasia y coagulación (Plaquetas) (IG:@doctor.paiva)

Introduction to Physiology Class

The instructor introduces the 36th physiology class focusing on blood physiology, specifically discussing hemostasis and coagulation.

Generalities of Hemostasis

• Hemostasis involves preventing blood loss through mechanisms like vascular spasm, platelet plug formation, blood clotting, and fibrous tissue proliferation.

• When a blood vessel is injured, the body initiates hemostasis to prevent excessive bleeding.

Vascular Spasm in Hemostasis

• Blood vessels contain smooth muscle in their middle layer.

• Trauma triggers a vascular spasm or vasoconstriction to reduce blood flow and prevent significant blood loss.

• Factors contributing to vascular spasm include local myospasm, local chemical factors from injured tissues and platelets, and nervous reflexes induced by pain or sensory impulses.

Mechanisms of Vascular Spasm

Explores the process of vascular spasm in hemostasis triggered by vessel injury.

Factors Contributing to Vascular Spasm

• Local myospasm plays a significant role in vasoconstriction post-injury.

• Platelets release thromboxane A2 upon direct damage to the vessel wall, enhancing vasoconstriction.

• The degree and duration of vascular spasm depend on the extent of trauma, lasting from minutes to hours to facilitate platelet plug formation.

Platelet Plug Formation

Discusses the formation of platelet plugs as part of hemostasis following minor vessel injuries.

Platelet Function and Formation

• Platelets originate from megakaryocytes in bone marrow.

• Megakaryocytes fragment into platelets released into circulation.

• Platelets lack nuclei but possess cellular characteristics like contractile proteins, endoplasmic reticulum for enzyme synthesis, mitochondria for ATP production, and enzymes for prostaglandin synthesis.

Characteristics of Platelets

Details the structural components and functions of platelets essential for their role in hemostasis.

Key Features of Platelets

• Platelets are not cells but exhibit cell-like properties with vital functions.

• They contain contractile proteins like myosin and thrombosthenin, endoplasmic reticulum for enzyme synthesis, mitochondria for ATP production, enzymatic systems synthesizing prostaglandins crucial for various processes.

Mechanism of Platelet Plug Formation

Explores how platelet plugs form through interactions with collagen and von Willebrand factor post-vessel injury.

Process of Platelet Plug Formation

• Damaged endothelium exposes collagen beneath it triggering platelet adhesion via glycoproteins on their membrane.

• Von Willebrand factor stabilizes this adhesion leading to stable plug formation.

Understanding Platelet Activation and Coagulation Cascade

In this section, the process of platelet activation and the coagulation cascade are discussed in detail, highlighting the role of various factors and proteins involved in these crucial physiological mechanisms.

Platelet Activation Process

• Platelets contain granules with ADP and serotonin.

• Serotonin acts as a vasoconstrictor, while ADP is vital for platelet aggregation.

• Upon release, healthy thrombi activate platelets expressing tissue factor on their membrane.

Platelet Aggregation and Clot Formation

• Platelets expel ADP and serotonin to bind to nearby platelets' membranes, initiating calcium release.

• Adjacent platelets activate glycoprotein Ib with ATP and thrombin, forming bridges between them.

• This leads to fibrin strands forming between platelets, crucial for clot formation.

Importance of Hemostasis

• Platelet aggregation is essential for sealing minor vessel ruptures daily.

• The coagulation process involves vessel injury, platelet adhesion, fibrin formation, and clot stabilization.

Coagulation Process and Fibrin Formation

This section delves into the steps involved in coagulation after vessel injury, emphasizing the significance of fibrin formation in wound healing.

Coagulation Steps

• Following vessel damage, a complex cascade triggers blood clotting within seconds to minutes.

• Fibroblasts invade clots post-coagulation to form connective tissue or dissolve clots naturally.

Factors Affecting Coagulation

• Coagulation balance relies on procoagulant vs. anticoagulant substances in blood plasma.

• Vessel rupture shifts balance towards procoagulants over anticoagulants for clot formation.

Thrombin Role in Fibrin Formation

• Thrombin catalyzes fibrinogen conversion into fibrin fibers post-prothrombin activation by protein activator complex.

• Fibrin mesh stabilizes clots with Factor XIII from plasma and platelets aiding in its formation.

Intrinsic and Extrinsic Pathways of Blood Coagulation

The discussion delves into the intrinsic and extrinsic pathways of blood coagulation, detailing the activation of Factor 10 and the involvement of various plasma proteins in these cascades.

Intrinsic Pathway

• The intrinsic pathway initiates with blood trauma, activating Factor 12, which then activates Factor 11, leading to the activation of Factor 9 in a cascade.

• Factor 3 on platelets' membrane, along with activated Factor 8 and calcium, activates Factor 10, concluding the intrinsic pathway.

Extrinsic Pathway

• The extrinsic pathway begins with trauma outside blood vessels causing endothelial damage and release of tissue factor. This triggers Factor 7 activation, subsequently activating Factor 10.

• Both pathways converge at activated Factor 10 initiating the common pathway that transforms prothrombin into thrombin.

Thrombin Function

• Thrombin not only converts fibrinogen to fibrin but also activates Factor 5 to accelerate prothrombin conversion. It plays a crucial role in positive feedback mechanisms during coagulation.

Anticoagulants in Blood Coagulation

Anticoagulants within blood vessels prevent clotting by repelling factors involved in coagulation through endothelial properties and inhibitory proteins.

Endothelial Anticoagulant Mechanisms

• Endothelium's smooth surface prevents intrinsic pathway activation via contact inhibition. A layer of glycocalyx with negative charge repels coagulation factors and platelets.

• Endothelial protein thrombomodulin binds thrombin to delay clotting while activating a plasma protein that inhibits Factors 5 and 8.

Blood-Based Anticoagulants

• Fibrin fibers formed during clotting absorb most thrombin; remaining thrombin combines with antithrombin III aided by heparin for further inactivation.

• Heparin enhances antithrombin III efficacy significantly by inhibiting multiple coagulation factors like Factors 12,11,10,and9.

Heparin as an Anticoagulant

Heparin acts as a potent anticoagulant by enhancing antithrombin III activity against various coagulation factors when released from mast cells or basophils.

Heparin Functionality

• Heparin combined with antithrombin III boosts its effectiveness manifold against clotting factors. This complex aids in removing several key factors involved in coagulation processes.

Fibrinolytic System Activation

The fibrinolytic system is triggered upon clot formation to dissolve fibrin clots through plasminogen activation on damaged tissues or endothelium surfaces.

Fibrinolysis Process

New Section

Explanation of the release and activation of tissue plasminogen activator (tPA) by damaged blood vessels and endothelium, leading to the breakdown of fibrin clots.

Release and Activation Process

• tPA is released by damaged blood vessels and endothelium.

• The release of tPA is slow from damaged vascular endothelium, taking days to occur.

• tPA activates plasminogen, converting it into plasmin.

New Section

Discussion on the role of plasmin in breaking down fibrin clots through its proteolytic activity.

Role of Plasmin in Clot Breakdown

• Plasmin acts on fibrin clots, transforming them into soluble products.

• Plasmin is a potent proteolytic enzyme capable of clot destruction.

• The action of plasmin results in the degradation of fibrin within the clot.