Hemodynamic Disorders,thromboembolism,shock Flashcards
The health of cells and tissues depends on the circulation of blood, which delivers oxygen and nutrients and removes wastes generated by cellular metabolism. Under normal conditions, as blood passes through capillary beds, pro- teins in the plasma are retained within the vasculature and there is little net movement of water and electrolytes into the tissues. This balance is often disturbed by pathologic conditions that alter endothelial function, increase vascular pressure, or decrease plasma protein content, all of which promote edema—accumulation of fluid resulting from a net outward movement of water into extravascular spaces. Depending on its severity and location, edema may have minimal or profound effects. In the lower extremities, it may only make one’s shoes feel snugger after a long sed- entary day; in the lungs, however, edema fluid can fill alveoli, causing life-threatening hypoxia.
True or false
Define hemostasis ,inadequate hemostasis leads to? Define thrombosis,embolism and what they can cause
What is the pathology counterpart of hemostasis and what three things do they both involve
Hemostasis is the process of blood clotting that prevents excessive bleeding after blood vessel damage. Normal hemostasis comprises a series of regulated processes that maintain blood in a fluid, clot-free state in normal vessels while rapidly forming a localized hemostatic plug at the site of vascular injury.
IThe pathologic counterpart of hemostasis is thrombosis, the formation of blood clot (throm bus) within intact vessels. Both hemostasis and thrombosis involve three elements: the vascular wall, platelets, and the coagulation cascade.
Inadequate hemostasis may result in hemorrhage, which can compromise regional tissue perfusion and, if massive and rapid, may lead to hypotension, shock, and death.
Con- versely, inappropriate clotting (thrombosis) or migration of clots (embolism) can obstruct blood vessels, potentially causing ischemic cell death (infarction). Indeed, throm boembolism lies at the heart of three major causes of morbidity and death in developed countries: myocardial infarction, pulmonary embolism, and cerebrovascular accident (stroke)
Define hyperemia and congestion
What is the difference between the two
Give an example of congestion systemically and locally
Hyperemia and congestion both refer to an increase in blood volume within a tissue but they have different underlying mechanisms.
Hyperemia is an active process resulting from arteriolar dilation and increased blood inflow, as occurs at sites of inflammation or in exercising skeletal muscle.
Hyperemic tissues are redder than normal because of engorgement with oxygenated blood.
Congestion is a passive process resulting from impaired outflow of venous blood from a tissue. Congested tissues have an abnormal blue-red color (cyanosis) that stems from the accumulation of deoxygen- ated hemoglobin in the affected area. In long-standing chronic congestion, inadequate tissue perfusion and persis- tent hypoxia may lead to parenchymal cell death and sec- ondary tissue fibrosis,
Example:cardiac failure
Locally-as a consequence of an isolated venous obstruc- tion.
What surfaces of hyperemic and congested tissues feel wet and ooze blood
, On microscopic examination acute and chronic pulmonary congestion is marked by?
On microscopic examination acute hepatic and chronic hepatic congestion is marked by?
The periportal hepatocytes, better oxygenated because of their proximity to hepatic arterioles, experience less severe hypoxia and may develop only reversible fatty change.true or false
B). In long-standing, severe hepatic congestion (most commonly associated with heart failure), hepatic fibro- sis (“cardiac cirrhosis”) can develop. Because the central portion of the hepatic lobule is the last to receive blood, centrilobular necrosis also can occur in any setting of reduced hepatic blood flow (including shock from any cause); there need not be previous hepatic congestion true or false
Cut surfaces
is marked by blood-engorged alveolar capillaries and variable degrees of alveolar septal edema and intra-alveolar hemorrhage.
In chronic pulmo- nary congestion, the septa become thickened and fibrotic, and the alveolar spaces contain numerous macrophages laden with hemosiderin (“heart failure cells”) derived from phago- cytosed red cells.
acute hepatic congestion, the central vein and sinusoids are distended with blood, and there may even be central hepatocyte dropout due to necrosis.
In chronic passive congestion of the liver, the Microscopic findings include centrilobular hepatocyte necrosis, hemorrhage, and hemosiderin-laden macrophages
How much of lean body weight is water and how much of it is intracellular
Where is the rest found?
How much percentage is in blood plasma
Define edema
When the extra vascular fluid collects in the pleural cavity what is it called?
I’m the peritoneal cavity what?
In pericardial cavity what?
Define anasarca
Approximately 60% of lean body weight is water, two thirds of which is intracellular. Most of the remaining water is found in extracellular compartments in the form of interstitial fluid; only 5% of the body’s water is in blood plasma.
edema is an accumulation of inter- stitial fluid within tissues. Or Edema
• Edema is the result of the movement of fluid from the vasculature into the interstitial spaces;
Extravascular fluid can also collect in body cavities such as the pleural cavity (hydrotho rax), the pericardial cavity (hydropericardium), or the perito- neal cavity (hydroperitoneum, or ascites).
Anasarca is severe, generalized edema marked by profound swelling of sub- cutaneous tissues and accumulation of fluid in body cavities.
Name five pathophysiological causes of edema and state two conditions under each that will cause those pathophysiologies
1.Increased Hydrostatic Pressure
a. Impaired Venous Return
Congestive heart failure Constrictive pericarditis
Ascites (liver cirrhosis)
Venous obstruction or compression
Thrombosis
External pressure (e.g., mass)
Lower extremity inactivity with prolonged dependency
During pregnancy, the extra fluid in the body and the pressure from the growing uterus can cause swelling (or “edema”) in the ankles and feet.
b.Arteriolar Dilation
Heat
Neurohumoral dysregulation
2.Reduced Plasma Osmotic Pressure (Hypoproteinemia)
Protein-losing glomerulopathies (nephrotic syndrome) Liver cirrhosis (ascites)
Malnutrition
Protein-losing gastroenteropathy
Decreased colloid osmotic pressure due to reduced
plasma albumin
• decreased synthesis (e.g., liver disease, protein
malnutrition)
• increased loss (e.g., nephrotic syndrome)
6.ncreased hydrostatic pressure
(heart failure)
3.Lymphatic Obstruction Inflammatory Neoplasia Postsurgical Postirradiation
- Sodium Retention
Excessive salt intake with renal insufficiency Increased tubular reabsorption of sodium
Renal hypoperfusion
Increased renin-angiotensin-aldosterone secretion
Renal failure
5.increased vascular permeability (Inflammation)
Acute inflammation Chronic inflammation Angiogenesis
Fluid movement is governed by two forces name them
What is the normal way hydro and osmo interact
What will cause movement of fluid into th interstitium and what will this cause?
How is excess edema fluid removed and how is it returned to the bloodstream
Define trans usage and exudate with respect to hydro and osmo pressure and specific gravity
Vascular hydrostatic pressure
Colloid osmotic pressure
(Produced by plasma proteins)
Normally, the outflow of fluid produced by hydrostatic pressure at the arteriolar end is neatly balanced by inflow due to the slightly elevated osmotic pressure at the venular end so there is only a small net outflow of fluid into the interstitial space and the fluid is drained by lymphatic vessels.
Either increased hydrostatic pressure or diminished colloid osmotic pressure causes increased movement of water into the interstitium .This in turn increases the tissue hydrostatic pressure, and eventually a new equilibrium is achieved.
Excess edema fluid is removed by lymphatic drainage and returned to the bloodstream by way of the thoracic duct
The edema fluid that accumulates owing to increased hydrostatic pressure or reduced intravascular colloid typi- cally is a protein-poor transudate; it has a specific gravity less than 1.012.
By contrast, because of increased vascular permeability, inflammatory edema fluid is a protein-rich exudate with a specific gravity usually greater than 1.020
What will cause local increase in intra vascular pressure and give an example of this and an e ample of generalized increased intravasvular pressure which causes systemic edema
Explain how increased hydrostatic pressure causes edema in CCf(explain the normal before explaining what happens in CCf)
Because secondary hyperaldosteronism is a common feature of generalized edema, salt restriction, diuretics, and aldosterone antagonists also are of value in the manage- ment of generalized edema resulting from other causes. True or false
Local increases in intravascular pressure can result from impaired venous return—for example, a deep venous thrombosis in the lower extremity can cause edema restricted to the distal portion of the affected leg.
General ized increases in venous pressure, with resultant systemic edema, occur most commonly in congestive heart failure
Several factors increase venous hydrostatic pressure in patients with congestive heart failure .The reduced cardiac output leads to hypoperfusion or blood flow to of the kidneys, triggering the renin-angiotensin-aldosterone axis and inducing sodium and water retention (secondary hyperaldosteronism).
In patients with normal heart function, this adaptation increases cardiac filling and cardiac output, thereby improving renal perfusion or blood flow to kidneys . But the failing heart often cannot increase its cardiac output in response to the compensatory increases in blood volume. Instead, a vicious circle of fluid retention, increased venous hydro- static pressures, and worsening edema ensues.
Unless cardiac output is restored or renal water retention is reduced (e.g., by salt restriction or treatment with diuretics or aldosterone antagonists) this downward spiral contin- ues.
Which protein accounts for almost half of plasma protein
What will cause reduced osmotic pressure which is a cause of edema
How is albumin lost in nephrotic syndrome
Which conditions will cause reduced albumin synthesis
How will low albumin levels cause edema
What causes a lymphatic obstruction and what will the obstruction lead to
How will lymphatic obstruction cause edema
the characteristic finely pitted appearance of the skin of the affected breast is called?
Under normal circumstances albumin accounts for almost half of the total plasma protein.
Low amounts of circulating albumin
Reduced synthesis of albumin
In nephrotic syndrome ,damaged glomerular capillaries become leaky, leading to the loss of albumin (and other plasma proteins) in the urine and the development of generalized edema.
Reduced albumin synthesis occurs in the setting of severe liver disease (e.g., cirrhosis) and protein malnutri- tion
low albumin levels leads to edema, reduced intravascular volume, renal hypoperfusion, and secondary hyperaldo- steronism. Unfortunately, increased salt and water reten- tion by the kidney not only fails to correct the plasma volume deficit but also makes the edema worse , since the primary defect—low serum protein—persists.
Inflammatory or neoplasticism conditions will cause the obstruction and it’ll in turn lead to
Impaired lymphatic drainage and consequent lymphedema usually result from a localized obstruction .Example:Infiltration and obstruction of superficial lymphat- ics by breast cancer may cause edema of the overlying skin;
peau d’orange (orange peel).
Lymph- edema also may occur as a complication of therapy. One relatively common setting for this clinical entity is in women with breast cancer who undergo axillary lymph node resection and/or irradiation, both of which can disrupt and obstruct lymphatic drainage, resulting in severe lymphedema of the arm.
How will sodium and water retention cause edema
Which parts of the body is edema usually encountered in
Microscopically how is edema seen as
Subcutaneous edema usually accumulates where? What is dependent edema
How does pitting edema occur
How does edema due to renal dysfunction manifest?
With pulmonary edema, the lungs often are two to three times their normal weight, and sectioning reveals frothy, sometimes blood-tinged fluid consisting of a mixture of air, edema fluid, and extravasated red cells. Brain edema can be localized (e.g., due to abscess or tumor) or general- ized, depending on the nature and extent of the pathologic process or injury. With generalized edema, the sulci are nar- rowed while the gyri are swollen and flattened against the skull.true or false
Excessive retention of salt (and its obligate associated water) can lead to edema by increasing hydrostatic pres- sure (due to expansion of the intravascular volume) and. reducing plasma osmotic pressure.
in subcutaneous tissues, lungs, and brain.
, . shows clearing and separation of the extracel- lular matrix elements.
Subcutaneous edema can be diffuse but usually accu- mulates preferentially in parts of the body positioned the greatest distance below the heart where hydrostatic pres- sures are highest. Thus, edema typically is most pronounced in the legs with standing and the sacrum with recumbency, a relationship termed dependent edema.
Finger pressure over edematous subcutaneous tissue displaces the interstitial fluid, leaving a finger-shaped depression; this appearance is called pitting edema.
Edema due to renal dysfunction or nephrotic syndrome often manifests first in loose con- nective tissues (e.g., the eyelids, causing periorbital edema).
What is the importance of recognizing subcutaneous edema,pulmonary edema and brain edema
vary, ranging from merely annoying to rapidly fatal. Subcutaneous edema is important to rec- ognize primarily because it signals potential underlying cardiac or renal disease; however, when significant, it also can impair wound healing or the clearance of infections.
Pulmonary edema is a common clinical problem that most frequently is seen in the setting of left ventricular failure but also may occur in renal failure, acute respiratory dis- tress syndrome (Chapter 11), and inflammatory and infec- tious disorders of the lung. It can cause death by interfering with normal ventilatory function; besides impeding oxygen diffusion, alveolar edema fluid also creates a favorable environment for infections.
Brain edema is life-threatening; if the swelling is severe, the brain can herniate (extrude) through the foramen magnum. With increased intracranial pressure, the brain stem vascular supply can be com- pressed. Either condition can cause death by injuring the medullary centers
What are the steps of hemostasis
Define primary and secondary hemostasis
In the Endothelium there is usually a state of balance between the procoagulant and anticoagulant activities or factors in the endothelium but once theres something that triggers injured or actuvates the endothelialt cells the balance shifts towards the procoagulant activities causing these things
Normal endothelial cells show anticoagulant factors
Vascularinjurycausestransientarteriolarvasoconstriction through reflex neurogenic mechanisms, augmented by local secretion of endothelin (a potent endothelium- derived vasoconstrictor) This effect is fleet- ing, however, and bleeding would quickly resume if not for the activation of platelets and coagulation factors.
• Endothelial injury exposes highly thrombogenic suben- dothelial extracellular matrix (ECM), facilitating platelet adherence, activation, and aggregation. The formation of the initial platelet plug is called primary hemostasis
- Endothelial injury also exposes tissue factor (also known as factor III or thromboplastin), a pro- coagulant glycoprotein synthesized by endothelial cells. Exposed tissue factor, acting in conjunction with factor VII is the major in vivo trigger of the coagula- tion cascade and its activation eventually culminates in the activation of thrombin,
Activated thrombin promotes the formation of an insolu- ble fibrin clot by cleaving fibrinogen; thrombin also is a potent activator of additional platelets, which serve to reinforce the hemostatic plug. This sequence, termed secondary hemostasis, results in the formation of a stable clot capable of preventing further hemorrhage
•
As bleeding is controlled, counterregulatory mecha- nisms (e.g., factors that produce fibrinolysis, such as tissuetype plasminogen activator) are set into motion to ensure that clot formation is limited to the site of injury
Endothelial cells are central regulators of hemostasis; the balance between the anti- and prothrombotic activities of endo- thelium determines whether thrombus formation, propa- gation, or dissolution occurs. Normal endothelial cells express a variety of anticoagulant factors that inhibit platelet aggregation and coagulation and promote fibrinolysis; after injury or activation, however, this balance shifts, and endothelial cells acquire numerous procoagulant activities
True or false
Name four things that can activate endothelial cells
True
Besides trauma, endothelium can be activated by microbial pathogens, hemodynamic forces, P and a number of pro-inflammatory mediators
Name and explain the anti thrombotic activities of the endothelium
State the functions of nitric oxide and prostaglandin I2 in antithrombin properties
How do heparin like molecules ,tissue factor pathway inhibitor and thrombomodulin inhibit coagulation
How does fibrinolysis occur
Antithrombotic Properties of Normal Endothelium
1.Inhibitory Effects on Platelets. Intact endothelium pre- vents platelets (and plasma coagulation factors) from engaging the highly thrombogenic subendothelial ECM. Nonactivated platelets do not adhere to normal endo- thelium; even with activated platelets, prostacyclin (i.e., prostaglandin I2 [PGI2]) and nitric oxide produced by endo- thelium impede their adhesion.
Both mediators also are potent vasodilators and inhibitors of platelet aggregation; their synthesis by endothelial cells is stimulated by a number of factors (e.g., thrombin, cytokines) produced during coagulation.
Endothelial cells also produce adeno- sine diphosphatase, which degrades adenosine diphos- phate (ADP) and further inhibits platelet aggregation
2.Inhibitory Effects on Coagulation Factors. These actions are mediated by factors expressed on endothelial surfaces, particularly heparin-like molecules, thrombomodulin, and tissue factor pathway inhibitor . The heparinlike molecules act indirectly: They are cofactors that greatly enhance the inactivation of thrombin (and other coagula- tion factors) by the plasma protein antithrombin III.
Throm bomodulin also acts indirectly: It binds to thrombin, thereby modifying the substrate specificity of thrombin, so that instead of cleaving fibrinogen, it instead cleaves and acti- vates protein C, an anticoagulant. Activated protein C inhibits clotting by cleaving and inactivating two proco- agulants, factor Va and factor VIIIa(5and 8a) it requires a cofactor, protein S, which is also synthesized by endothelial cells.
Finally, tissue factor pathway inhibitor (TFPI) directly inhibits tissue factor–factor VIIa complex and factor Xa.
Fibrinolysis. Endothelial cells synthesize tissuetype plasminogen activator(tPA) a protease that cleaves plasminogen to plasmin; plasmin, in turn, cleaves fibrin to degrade thrombi.
State and explain the prothrombin properties of an injured or activated endothelium
Endothelium
Activation of Platelets. Endothelial injury brings platelets into contact with the subendothelial ECM, which includes among its constituents von Willebrand factor (vWF), a large multimeric protein that is synthesized by EC. vWF is held fast to the ECM through interactions with collagen and also binds tightly to Gp1b, a glycoprotein found on the surface of platelets. These interactions allow vWF to act as a sort of molecular glue that binds platelets tightly to denuded vessel walls (Fig. 3–7).
Activation of Clotting Factors. In response to cytokines (e.g., tumor necrosis factor [TNF] or interleukin-1 [IL-1]) or certain bacterial products including endotoxin, endothelial cells produce tissue factor, the major in vivo activator of coagulation, and downregulate the expression of thrombo- modulin. Activated endothelial cells also bind coagulation factors IXa and Xa (see further on), which augments the catalytic activities of these factors.
AntifibrinolyticEffects. :Activatedendothelialcellssecrete plasminogen activator inhibitors (PAIs), which limit fibrinoly- sis and thereby favor thrombosis
Endothelial cells stimulated by injury or inflammatory cytokines upregulate expression of procoagulant factors (e.g., tissue factor) that promote clotting, and downregu- late expression of anticoagulant factors.
True or false
What is the shape of platelets and how do they function
Platelet function depends on several integrin family glyco- protein receptors, a contractile cytoskeleton, and two types of cytoplasmic granules. State them
After vascular injury, platelets encounter ECM constituents (collagen is most important) and adhesive glycoproteins such as vWF. This sets in motion a series of events that lead to ?
True
Platelets are anucleate cell fragments shed into the blood- stream by marrow megakaryocytes. They play a critical role in normal hemostasis by forming a hemostatic plug that seals vascular defects, and by providing a surface that recruits and concentrates activated coagulation factors.
α granules, which express the adhesion molecule P-selectin on their membranes and contain
fibrinogen, fibronectin, factors V and VIII, platelet factor-4 (a heparin-binding chemokine), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β)
• Densebodies(δgranules),whichcontainadeninenucleo- tides (ADP and ATP), ionized calcium, histamine, sero- tonin, and epinephrine
platelet adhesion, (2) platelet activation, and (3) plate- let aggregation
What is hemorrhage,what increases the risk of hemorrhage ,
Name three other cases of hemorrhage
Hemorrhage, defined as the extravasation of blood from vessels,
The risk of hemorrhage (often after a seemingly insignificant injury) is increased in a wide variety of clinical disorders collectively called hemorrhagic diatheses. Trauma, atherosclerosis, or inflammatory or neoplastic erosion of a vessel wall also may lead to hemorrhage, which may be extensive if the affected vessel is a large vein or artery.
State and explain four ways hemorrhage may manifest clinically
The clinical significance of any particular hemorrhage depends on?
Rapid loss of up to 20% of the blood volume, or slow losses of even larger amounts, may have little impact in healthy adults; greater losses, however, can cause hemor rhagic (hypovolemic) shock . True or false
Hemorrhage may be external or accumulate within a tissue as a hematoma, which ranges in significance from trivial (e.g., a bruise) to fatal (e.g., a massive retroperito- neal hematoma resulting from rupture of a dissecting aortic aneurysm) (Chapter 9).
Large bleeds into body cavities are given various names according to location—hemothorax, hemopericar dium, hemoperitoneum, or hemarthrosis (in joints). Exten- sive hemorrhages can occasionally result in jaundice from the massive breakdown of red cells and hemoglobin.
• Petechiae are minute (1 to 2 mm in diameter) hemor- rhages into skin, mucous membranes, or serosal sur- faces (Fig. 3–4, A); causes include low platelet counts (thrombocytopenia), defective platelet function, and loss of vascular wall support, as in vitamin C deficiency (Chapter 7).
• Purpura are slightly larger (3 to 5 mm) hemorrhages. Purpura can result from the same disorders that cause petechiae, as well as trauma, vascular inflammation (vasculitis), and increased vascular fragility.
• Ecchymoses are larger (1 to 2 cm) subcutaneous hemato- mas (colloquially called bruises). Extravasated red cells are phagocytosed and degraded by macrophages; the characteristic color changes of a bruise are due to the enzymatic conversion of hemoglobin (redblue color) to bilirubin (blue-green color) and eventually hemosiderin (golden-brown)
the volume of blood lost and the rate of bleed- ing,site of hemorrhage(bleeding that would be trivial in the subcutaneous tissues can cause death if located in the brain
True
What will cause iron deficiency and what won’t cause iron deficiency
Finally, chronic or recurrent external blood loss (e.g., due to peptic ulcer or menstrual bleeding) frequently culminates in iron deficiency anemia as a con- sequence of loss of iron in hemoglobin. By contrast, iron is efficiently recycled from phagocytosed red cells, so inter- nal bleeding (e.g., a hematoma) does not lead to iron deficiency.
How does platelet adhesion help in clot formation
Deficiency in vWF results in which disease?
Deficiency in Gp1b results in which disease?
Endothelial injury exposes the underlying basement mem- brane ECM; platelets adhere to the ECM primarily through binding of platelet GpIb receptors to vWF.true or false
Platelet Adhesion
Platelet adhesion initiates clot formation and depends on vWF and platelet glycoprotein Gp1b. Under shear stress (e.g., in flowing blood), vWF (von Willebrand factor undergoes a conformational change, assuming an extended shape that allows it to bind simultaneously to collagen in the ECM and to platelet Gp1b (glycoprotein 1b).
The importance of this adhesive interac- tion is highlighted by genetic deficiencies of vWF and Gp1b, both of which result in bleeding disorders von Willebrand disease and Bernard-Soulier disease (a rare condition), respectively.
How does platelet activation help in clotting
Platelet Activation
Platelet adhesion leads to an irreversible shape change and
secretion (release reaction) of both granule types—a process
termed platelet activation. Calcium and ADP released from
δ granules are especially important in subsequent events,
since calcium is required by several coagulation factors and
ADP is a potent activator of resting platelets. Activated
platelets also synthesize thromboxane A (TxA ) ,a prostaglandin that activates additional nearby plate- lets and that also has an important role in platelet aggrega- tion .During activation, platelets undergo a dramatic change in shape from smooth discs to spheres with numerous long, spiky membrane extensions, as well as more subtle changes in the make-up of their plasma membranes. The shape changes enhance subsequent aggre- gation and increase the surface area available for interac- tion with coagulation factors. The subtle membrane changes include an increase in the surface expression of negatively charged phospholipids, which provide binding sites for both calcium and coagulation factors, and a conformation change in platelet GpIIb/IIIa that permits it to bind fibrinogen.
How does platelet aggregation help in clot formation
Which disease shows the importance of platelet aggregation
Concurrent activation of the coagulation cascade gener- ates thrombin, which stabilizes the platelet plug through two mechanisms. Explain those two mechanisms
State two functions of thrombin in inflammation
Red cells and leukocytes are also found in hemostatic plugs. Leukocytes adhere to platelets by means of P- selectin and to endothelium by various adhesion molecules ;they contribute to the inflammatory response that accompanies thrombosis. True or false
The GpIIb/IIIa receptors on activated platelets form bridg- ing crosslinks with fibrinogen, leading to platelet aggregation.
• Concomitant activation of thrombin promotes fibrin deposition, cementing the platelet plug in place.true or false
Platelet aggregation follows platelet adhesion and activa- tion, and is stimulated by some of the same factors that induce platelet activation, such as TxA2. Aggregation is promoted by bridging interactions between fibrinogen and GpIIb/IIIa receptors on adjacent platelets .
The importance of this interaction is emphasized by a rare inherited deficiency of GpIIb/IIIa (Glanzmann thrombas- thenia), which is associated with bleeding and an inability of platelets to aggregate.
Thrombinactivatesaplateletsurfacereceptor(protease- activated receptor [PAR]), which in concert with ADP and TxA2 further enhances platelet aggregation. Platelet contraction follows, creating an irreversibly fused mass of platelets that constitutes the definitive secondary hemo static plug.
• Thrombin converts fibrinogen to fibrin (discussed shortly) within the vicinity of the plug, cementing the platelet plug in place.
Thrombin also promotes inflammation by stimulating neutrophil and monocyte adhesion and by generating chemotactic fibrin split products during fibrinogen cleavage.
True
How do platelet endothelial interactions affect clot formation
The clinical utility of aspirin (an irreversible cyclooxygenase inhibitor) in lowering the risk of coronary thrombosis resides in its ability to do what?
The interplay of platelets and endothelium has a profound impact on clot formation. For example, prostaglandin PGI2 (synthesized by normal endothelium) is a vasodilator and inhibits platelet aggregation, whereas TxA2 (synthesized by activated platelets, as discussed above) is a potent vaso- constrictor. The balance between the opposing effects of PGI2 and TxA2 varies: In normal vessels, PGI2 effects domi- nate and platelet aggregation is prevented, whereas endo- thelial injury decreases PGI2 production and promotes platelet aggregation and TxA2 production.
To permanently block TxA2 production by platelets, which have no capacity for protein synthesis. Although endothelial PGI2 production is also inhibited by aspirin, endothelial cells can resynthesize cyclooxygenase, thereby overcoming the blockade. In a manner similar to that for PGI2, endothelium-derived nitric oxide also acts as a vaso- dilator and inhibitor of platelet aggregation
What is coagulation cascade
Explain how it occurs
Blood coagulation is divided into two. State and explain em
Each reaction in the pathway depends on ?These components typically are assembled where? and are held together by what?.
the sequen- tial cascade of activation can be likened to a “dance” of complexes, with coagulation factors being passed succes- sively from one partner to the next. True or false
The coagulation cascade is a successive series of ampli- fying enzymatic reactions. Coagulation occurs via the sequential enzymatic conver- sion of a cascade of circulating and locally synthesized proteins.
Thrombin proteolyzes fibrinogen into fibrin monomers that
polymerize into an insoluble gel; this gel encases platelets and other circulating cells in the definitive secondary hemostatic plug. Fibrin polymers are stabilized by the cross-linking activity of factor XIIIa, which also is activated by thrombin.
Blood coagulation traditionally is divided into extrinsic and intrinsic pathways, converging at the activation of factor X .The extrinsic pathway was so desig- nated because it required the addition of an exogenous trigger (originally provided by tissue extracts); the intrinsic pathway only required exposing factor XII (Hageman factor) to a negatively charged surface (even glass suffices). The extrinsic pathway is the most physi- ologically relevant pathway for coagulation occurring after vascular damage; it is activated by tissue factor, a membrane-bound glycoprotein expressed at sites of injury.
the assembly of a complex composed of an enzyme (an activated coagula- tion factor), a substrate (a proenzyme form of the next coag- ulation factor in the series), and a cofactor (a reaction accelerator).
on a phospholipid surface (provided by endothelial cells or platelets)
interactions that depend on calcium ions (explaining why blood clotting is prevented. by calcium chelators)
