Physiology Hemostasis and Blood Coagulation

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Questions and Answers

What are the three major steps in hemostasis?

Vascular constriction, platelet plug formation, and blood coagulation.

The first line of defense in hemostasis involves the formation of a platelet plug.

False

What is the key factor in platelet activation and adherence to the damaged vessel wall?

Thromboxane A2

ADP

Collagen

All of the above (correct)

Von Willebrand factor acts as a(n) ______ bridge between subendothelial collagen and the glycoprotein Ib receptor.

adhesion Signup and view all the answers

Fibrinolysis is the process of breaking down the fibrin clot, primarily activated by plasminogen activators.

True Signup and view all the answers

What is the role of thrombin in the clotting process?

All of the above Signup and view all the answers

What are the two major pathways leading to prothrombin activator formation?

The extrinsic pathway and the intrinsic pathway. Signup and view all the answers

The extrinsic pathway of coagulation is initiated by _____ :

Tissue factor released from damaged cells and tissues Signup and view all the answers

The extrinsic pathway is generally slower than the intrinsic pathway.

False Signup and view all the answers

The clotting cascade typically involves a series of inactive proteases that are activated in a cascade-like fashion.

True Signup and view all the answers

What are two important functions of the glycocalyx in preventing clotting?

The glycocalyx repels platelets and clotting factors, and it also binds thrombomodulin, which activates Protein C to inactivate clotting factors. Signup and view all the answers

What is the primary mechanism of action of heparin, a natural anticoagulant?

Binds and potentiates antithrombin III, increasing its effectiveness. Signup and view all the answers

What are the two primary clinical uses for heparin?

Heparin is used to prevent clotting during blood collection and for acute treatments of clotting disorders. Signup and view all the answers

What is the mechanism of action of coumarins, a group of synthetic anticoagulants?

Inhibits VKOR C1, depleting active vitamin K Signup and view all the answers

Coumarins are typically administered in the acute setting due to their rapid onset of action.

False Signup and view all the answers

Match the clinical coagulation tests with their respective primary functions.

Bleeding Time = Assesses the extrinsic and common pathways of coagulation. Prothrombin Time (PT) = Measures the integrity of the intrinsic pathway of coagulation. Activated Partial Thromboplastin Time (aPTT) = Reflects platelet function and number. International Normalized Ratio (INR) = Evaluates the activity of specific coagulation factors. Tests of Other Clotting Factors = Standardized ratio used to monitor the effectiveness of anticoagulation therapy. Signup and view all the answers

Study Notes

Physiology Study Notes

The document is a set of study notes on Hemostasis and Blood Coagulation.
The notes are written by Tasneem Jarwan and edited by Tasneem Jarwan, with Ebaa Alzayadneh as the doctor.
The notes are a compilation from various sources. Topics covered include vascular constriction, platelet plug formation, blood clotting, and clot extension.
The notes are part of a larger Physiology course and are related to the Guyton and Hall Textbook of Medical Physiology, 13th edition.

Hemostasis and Blood Coagulation

Hemostasis is a process that our body uses to prevent blood loss.
It is a multi-step process involving blood components(platelets) that cause the fluid in our blood to change to gel-like texture, and makes network near the edges of cuts to stop bleeding.
The process of stopping bleeding through replacing damaged tissues with easy healing process.

Events in Hemostasis

Vascular constriction: Blood vessels contract immediately after a cut, reducing blood flow to the injured area. Mechanisms include local myogenic spasm (from the blood vessel itself), local autacoid factors (from active platelets, surrounding tissue, immune cells), and nervous reflexes (from pain receptors).
Formation of a platelet plug: When a small blood vessel is cut, platelets adhere to the exposed collagen in the vessel wall. These platelets swell and change shape. Next, the platelets release granules containing ADP, thromboxane A₂(which stimulates even more platelets to adhere), and other factors that attract more platelets and causing the platelets to aggregate. (The aggregated platelets, along with some other blood components, form the platelet plug.)
Formation of a blood clot: If the platelets don't completely stop bleeding, then it proceeds to the blood clot formation sequence. The platelets release more factors that start a cascade of reactions involving clotting factors (inactive proteins) that eventually activate thrombin. Thrombin is an enzyme that converts fibrinogen (a soluble protein) to fibrin (an insoluble protein). This fibrin forms a mesh that traps blood cells and platelets forming a blood clot. The process includes several factors like fibrin stabilizing factor and covalent bonds to stabilize the clot and reinforce it.

Stages of Clotting

Extrinsic or Intrinsic pathway: These pathways lead to prothrombinase formation, which converts prothrombin to thrombin.
Prothrombinase converts prothrombin to thrombin: This is the rate-limiting step crucial for initiating rapid blood clotting. Thrombin converts fibrinogen into fibrin.
Thrombin converts fibrinogen(soluble) to fibrin(insoluble): The insoluble fibrin forms a mesh trapping blood cells and platelets, creating a blood clot, which stops bleeding.

Platelet Function

Platelets are fragmented megakaryocytes released via capillaries.
They are disc-shaped cells with a short lifespan (8-12 days).
They lack nuclei and can't reproduce.
They contain actin and myosin, and other specialized proteins that help in clotting.
They release granules containing factors that enhance clot formation.

Platelet Membranes

Surface glycoproteins repel intact endothelium.
They adhere to collagen and injured endothelium when exposed.
Membrane phospholipids activate blood clotting

Platelet Plug Formation

Upon activation, platelets become sticky, irregular in shape and form pseudopods.
They adhere to exposed collagen and von Willebrand factor (vWF).
Other platelets accumulate, adhering, and contracting, forming the plug and initiating the clotting process.

Thrombocytopenia

Low platelet counts lead to bleeding problems, such as bruising and bleeding from small venules or capillaries.
Symptoms such as petechiae or thrombocytopenic purpura.
Treated with platelet infusions.

Thrombi and Emboli

Thrombi are abnormal clots, and emboli are clots that detach from their original location.
Emboli occur from endothelial damage or slow blood flow.
Treatments often involve tPA or embolectomy for clots.

Pulmonary Emboli

These emboli usually originate from deep leg veins.
They can occlude (block) pulmonary arteries, causing life-threatening issues.
tPA (tissue plasminogen activator) therapy is an effective treatment occasionally.

Disseminated Intravascular Coagulation (DIC)

DIC is widespread coagulation in small vessels caused by massive tissue damage.
The bleeding is a result of the body's clotting factors being depleted.

Clotting Factors

A set of proteins involved in the coagulation cascade.
Some are inactive enzymes that become active through a cascade-like activation sequence.
Clotting factors include specific enzymes and non-enzyme substances like calcium and vitamin K-dependent proteins.
Different factors activate and/or are stimulated by other factors (or in response to other factors) and activate the next factors in a chain (or cascade) leading to the final clot formation.

Vitamin K Deficiency

Vitamin K is essential for the carboxylation of glutamic acid residues in several clotting factors.
This process is critical for their proper function in the coagulation cascade.
Vitamin K is produced by bacteria in the intestine. Any deficiency may result from fat malabsorption or lack of bile production from the liver, as Bile is essential to digest fat effectively, which in turn is essential to absorb fat-soluble vitamins.
It can be injected to be used for patients with liver or biliary disease during or before surgery.

Hemophilia

Hemophilia A involves deficiency of Factor VIII or IX.
Both disorders impair the intrinsic pathway activation in blood clotting.
Hemophilia A is the most common type.
Clinically evident through bleeding after minor traumas.
Both Factor VIII and IX are found on the X chromosome.

Factor VIII Deficiency

Factor VIII has two components (Large and Small).
Deficiency of the small component causes Hemophilia A.
Deficiency of the large (von Willebrand factor) component causes von Willebrand disease which can lead to decreased platelet function.

Vitamin K

Important for synthesizing clotting factors, especially prothrombin and factors VII, IX, and X.

Blood Clotting Tests

Bleeding time: Reflects platelet function/number, typically normal within 1-6 minutes for a small cut.
Clotting time, measures the overall time it takes for a blood sample to clot, normally between 6-10 minutes.
Prothrombin time (PT), assess the extrinsic and common pathways, usually around 12 seconds though it can vary dependent on the tissue factor batch (and hence standardized by the International Sensitivity Index (ISI)).
Activated partial thromboplastin time (aPTT), measures the integrity of the intrinsic pathway, normally around 35 seconds.

Anti-Coagulation In Vitro

Siliconized containers prevent factor VII and platelet activation.
Heparin is used in blood collection, heart-lung, and kidney machines.
Calcium chelators (citrate, EDTA) are used in blood collection and blood storage.

Prevention of Clotting

Endothelial smoothness reduces platelet and clotting factor adherence.
Mucopolysaccharides (glycocalyx) coating repels platelets and clotting factors.
Thrombomodulin, bound to endothelium, binds thrombin which can then activate Protein C, in turn inhibiting Factors V and VIII, reducing the risk of clot formation.
Damage to the glycocalyx may lead to the activation of factor XII, which initiates the intrinsic pathway of clotting.
An exposed collagen will lead to even more robust clotting. -Negative feedback mechanisms also help in regulating the process of clotting, reducing unnecessary blood clotting throughout the body.

Synergistic Effect Between Extrinsic and Intrinsic Pathway

Tissue injury activates the extrinsic pathway.
Exposure of tissue factor XII and platelets to collagen activates the intrinsic pathway.
Extrinsic pathway is explosive (clotting in under 15 seconds), while the intrinsic pathway works more slowly (1-6 minutes).
Both pathways work together and eventually the clot needs to be broken down using plasminogen/plasmin.

Key Steps in Blood Clotting

Prothrombin activator converts prothrombin to thrombin.
Thrombin converts fibrinogen to fibrin fibers.
Fibrin fibers (with the help of fibrins stabilizing factor become cross-linked, forming a stronger clot).

Clot Retraction

Begins within 20-60 minutes after clot formation.
Fibrin binds to damaged vessel walls.
Platelets bind to multiple fibrin fibres.
Platelets use contractile proteins (actin, myosin, thrombosthenin) and factor XIII to pull the fibrin fibers together, tightening the clot and sealing off the vascular defect.

Generation of Prothrombin Activator

Two pathways exist for prothrombin activator generation: extrinsic and intrinsic.
Extrinsic: Trauma to the vessel wall or adjacent tissues initiates it releasing tissue factor leading to fast response.
Intrinsic: Trauma to the blood or exposure to collagen initiates it, leading to slow response.
These pathways share a common pathway requiring clotting factors mostly inactive (mostly enzymes), which are activated at various steps for clot formations.

Clot Lysis

Plasminogen is a protein in the blood trapped in the clot.
Injured tissues release tissue plasminogen activator.
This activates plasminogen to plasmin (an enzyme).
Plasmin breaks down fibrin fibres involved in clot formation and several other clotting factors, thus re-opening repaired small blood vessels.

Causes of Excessive Bleeding

Hepatocellular disease, vitamin K deficiency, Hemophilia, and low platelet count.

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Test your knowledge on hemostasis and blood coagulation with this quiz. The content is based on a comprehensive set of study notes covering key topics such as vascular constriction, platelet plug formation, and blood clotting mechanisms. Ideal for students studying the Guyton and Hall Textbook of Medical Physiology.