Familial Hypercholesterolemia and Hemostasis

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Questions and Answers

What is the inheritance pattern of Familial Hypercholesterolemia (FH)?

Autosomal recessive

X-linked recessive

Mitochondrial

Autosomal dominant (correct)

What is the primary treatment goal for FH?

Lowering HDL cholesterol levels

Increasing triglycerides

Increasing LDL cholesterol levels

Lowering LDL cholesterol levels (correct)

What is the typical effect of a low-fat, high-carbohydrate diet on LDL cholesterol levels in FH patients?

A significant reduction (greater than 50%)

A moderate reduction (around 30-40%)

A minimal reduction (around 10-20%) (correct)

No significant change

Which of the following is NOT a treatment option for FH?

Insulin therapy (C) Signup and view all the answers

If a heterozygous individual with FH has a child, what is the probability that the child will inherit the mutant LDLR allele?

50% (B) Signup and view all the answers

What is the role of tissue plasminogen activator (t-PA) in clot stabilization and resorption?

t-PA converts plasminogen into plasmin, which breaks down fibrin. (B) Signup and view all the answers

What is the primary function of fibrin in clot stabilization?

Fibrin provides a stable scaffolding that prevents further bleeding. (B) Signup and view all the answers

Which of the following events occurs during primary hemostasis?

Release of von Willebrand factor (vWF) and subsequent platelet activation. (A) Signup and view all the answers

What is the significance of the D-dimer test in clinical practice?

The D-dimer test detects the presence of fibrin-split products in the blood, indicating ongoing clotting. (B) Signup and view all the answers

Which of the following statements about the clotting pathway is CORRECT?

The intrinsic pathway is triggered by the activation of tissue factor, initiating the clotting cascade. (D) Signup and view all the answers

What is the primary function of heparin-like molecules in clotting inhibition?

Heparin-like molecules activate antithrombin, which then inhibits the conversion of fibrinogen into fibrin. (B) Signup and view all the answers

How does arteriolar vasoconstriction contribute to hemostasis?

Arteriolar vasoconstriction reduces blood flow to the injured area, minimizing blood loss. (A) Signup and view all the answers

What is the main purpose of the counterregulatory mechanisms that come into play during clot stabilization?

To prevent excessive clotting and ensure that the blood remains fluid. (A) Signup and view all the answers

What is the risk of a child inheriting Factor V Leiden if one parent carries the mutant allele?

50% (D) Signup and view all the answers

Which condition is characterized by autoantibodies binding to heparin and platelet membrane proteins?

Heparin induced thrombocytopenia (HIT) (A) Signup and view all the answers

What leads to widespread clotting in the microcirculation in Disseminated Intravascular Coagulation (DIC)?

Infection or shock (C) Signup and view all the answers

What happens to cellular injury during shock initially?

It is reversible (A) Signup and view all the answers

Which type of shock is caused by issues related to the heart's pumping ability?

Cardiogenic shock (D) Signup and view all the answers

What is considered the most important factor in Virchow's Triad that contributes to clot formation?

Endothelial injury (D) Signup and view all the answers

Which of the following conditions is associated with hypercoagulability?

Atrial fibrillation (B) Signup and view all the answers

Which laboratory deficiency is linked to increased risk of venous thromboembolism due to hypercoagulability?

Protein C and S deficiency (A) Signup and view all the answers

What therapy is used for antiplatelet treatment in patients at risk for blood clots?

Asprin (ASA) (C) Signup and view all the answers

Which of the following factors is NOT considered a risk factor for hypercoagulability?

Chronic hydration (C) Signup and view all the answers

Which medication can be used to lyse an existing blood clot?

tPA (A) Signup and view all the answers

Which condition involving prolonged immobility can increase the risk of clot formation?

Recent surgery (D) Signup and view all the answers

Factor V Leiden mutation is a genetic predisposition associated with which condition?

Hypercoagulability (C) Signup and view all the answers

What is the primary mechanism behind neurogenic shock?

Spinal cord injury (A) Signup and view all the answers

What is a major consequence of endothelial activation in septic shock?

Increased vascular permeability (A) Signup and view all the answers

Which cytokine primarily initiates the clotting cascade in septic shock?

TNF (D) Signup and view all the answers

What effect does sepsis have on insulin release?

Inhibits insulin release (B) Signup and view all the answers

What is a potential complication of hyperglycemia in septic shock?

Diminished ability to fight infection (B) Signup and view all the answers

What is the result of mitochondrial damage during septic shock?

Decreased oxygen and nutrient delivery (C) Signup and view all the answers

What characterizes the irreversible stage of shock?

Organ failure (C) Signup and view all the answers

Which of the following is NOT a stage of shock?

Severe shock (D) Signup and view all the answers

How do healthy endothelial cells contribute to anticoagulation?

They release tissue factor VIIa complexes that block VII activity. (D) Signup and view all the answers

What is the primary function of thrombomodulin in the clotting process?

It directly inhibits thrombin's ability to activate platelets and other coagulation factors. (D) Signup and view all the answers

What is the mechanism of action of t-PA in dissolving clots?

It binds to fibrin and activates plasminogen, leading to clot breakdown. (C) Signup and view all the answers

What is the primary mechanism of action of warfarin as an anticoagulant?

It inhibits the synthesis of clotting factors II, VII, IX, and X by depleting vitamin K reserves. (B) Signup and view all the answers

Which of these choices is NOT a direct effect of heparin?

Inhibits the production of clotting factors. (D) Signup and view all the answers

Why is a 'bridge to warfarin' often used with heparin?

Warfarin can temporarily increase clotting potential by inhibiting the production of protein C and S, which are anticoagulants. (A) Signup and view all the answers

How do P2Y12 inhibitors work to prevent clot formation?

They block the receptor for ADP on platelets, inhibiting platelet aggregation. (A) Signup and view all the answers

Which of the following directly affects the extrinsic pathway of the coagulation cascade?

Warfarin (A) Signup and view all the answers

Study Notes

Pathogen 4.1 Vessels - Objectives

Illustrate fluid distribution between intravascular and extravascular compartments, applying normal circulation principles.
Distinguish oncotic and hydrostatic causes of edema, using clinical examples.
Analyze the role of renal pathology in fluid balance disruption.
Discuss heart pathology regarding fluid balance.
Analyze hemorrhage and provide clinically important examples.
Illustrate normal hemostasis, the role of endothelial cells, platelets, and coagulation proteins; addressing pathologic and medicinal implications.
Discuss thrombus and embolus formation.
Analyze hypercoagulability and its causes.
Illustrate infarction and its pathogenesis.
Illustrate shock and its pathogenesis.
Differentiate major mechanical vascular diseases, including congenital causes.
Illustrate arteriosclerosis.
Illustrate aneurysm forms and their formation.
Discuss familial hypercholesterolemia (phenotypes, inheritance, etiology, incidence, pathogenesis, etc).
Analyze essential and secondary hypertension, relating it to pathogenesis.
Distinguish aortic dissection types and their clinical consequences.
List the pathogenesis types of vasculitis and vascular tumor.

Fluid Balance

Two opposing forces drive fluid balance in the body: hydrostatic pressure and oncotic pressure (colloid osmotic pressure).
Hydrostatic pressure typically wins, but lymphatics remove excess fluid.

Fluid Balance (IO:1)

Opposing forces: hydrostatic and oncotic pressures
Hydrostatic fluid pressure often wins, but lymphatics clean up extra fluid.

Causes of Edema

Venous return issues (e.g., congestive heart failure, constrictive pericarditis, ascites).
Venous obstruction or compression.
Thrombosis.
External pressure (tumors).
Lower extremity inactivity.
Protein-losing conditions (nephrotic syndrome, liver cirrhosis).
Malnutrition.
Lymphatic obstruction.
Inflammatory diseases (inflammatory dz).
Tumors (neoplasm).
Post-surgical or post-irradiation issues.
Excessive sodium intake or reduced kidney function.
Increased Na+ uptake.
Renal hypoperfusion.
Increased renin-angiotensin-aldosterone secretion.

Terms

Edema: Fluid accumulation in tissues due to net water movement into extravascular spaces.
May manifest as swollen feet or pulmonary edema.
Hyperemia: Increased arterial blood flow.
Congestion: Increased venous blood flow.
Hemostasis: Blood clotting process.
Thrombosis: Formation of a stationary blood clot.
Embolism: A blood clot or other matter that has moved to a different part of the body.
Infarction: Tissues die due to ischemia.
Effusion: Extravascular fluid collection in body tissues.

Renin, Angiotensin, Aldosterone

Renin activates angiotensinogen, converting it to angiotensin I.
Lungs convert angiotensin I to angiotensin II using ACE.
Angiotensin II stimulates aldosterone release, increasing blood pressure.
Aldosterone increases Na+ reabsorption, leading to water retention and a rise in blood volume.

BP Regulation

Blood pressure depends on cardiac output and peripheral vascular resistance.
Cardiac output is a function of heart rate and stroke volume, which depends on filling pressure and myocardial contractility (influenced by alpha and beta adrenergic inputs).

Hypertension

Elevated blood pressure (consistently above 140/90 mm Hg).
Major complications: Cardiac hypertrophy, heart failure, stroke (CVA), dissection.
Types: Primary (essential, idiopathic) and secondary.

Hemorrhage Terms

Hemorrhage: Blood leakage from vessels.
Hematoma: Blood mass.
Petechiae/Purpura: Small hemorrhages into skin, mucous membranes, or serosal surfaces (often due to low platelets).
Ecchymoses: Bruises.
RBCs degrade to form hemosiderin (golden-brown).
Bilirubin (blue-green).

Clinical Tie-ins for Hemorrhage

Massive hemorrhage leads to hypovolemic shock and exsanguination.
Hematoma compresses tissues and may cause compartment syndrome.
Intracranial hemorrhage results in stroke or death.

Hemostasis Review

Arteriolar vasoconstriction reduces blood flow close to the injury site.
Primary hemostasis involves platelet aggregation to form a plug.
Secondary hemostasis involves activation of clotting factors and fibrin formation to create a stable clot.
Clot stabilization, and subsequent breakdown of the clot, are regulated by counterregulatory mechanisms.

Clinical Point (IO:6)

D-dimer is a fibrinogen breakdown byproduct.
Its presence in the blood indicates clotting activity.
Measured in blood tests (D-dimer test) to detect clotting.

Clotting Pathway

PT/INR: Measures the extrinsic pathway.
PTT: Measures the intrinsic pathway.

Clotting Inhibition

Heparin-like molecules activate antithrombin to prevent fibrin formation.
Endothelial cells switch between procoagulant and anticoagulant states to maintain hemostasis.
Thrombomodulin and protein C receptor inhibit thrombin's pro-coagulant effects.
t-PA aids in clot breakdown.

Medicinal Clotting Inhibition

Warfarin inhibits vitamin K-dependent clotting factors.
Heparin activates antithrombin.
Xa inhibitors directly inhibit clotting factors.
Aspirin is an antiplatelet drug.
P2Y12 inhibitors block ADP receptors.

Clinical Points (IO:6)

Using heparin before warfarin is common as warfarin inhibits Protein C and S which leads to a temporary procoagulant state.
Other clinical conditions: Factor V Leiden mutation, Protein C and S deficiency, antithrombin III deficiency, Von Willebrand's disease.
Medical interventions for blood clots: Anticoagulants (heparin, NOACs), Antiplatelets (ASA, P2Y12 inhibitors), Thrombolytics (tPA).

Virchow's Triad

Endothelial injury is crucial for thrombosis.
Abnormal blood flow (e.g., stasis, turbulence) contributes.
Hypercoagulability predisposes to clotting.

Hypercoagulability

Conditions increasing clotting risk: Factor V Leiden mutation, Antithrombin III deficiency, protein C and S deficiency, immobility, cancer, surgery, tissue injury, prosthetic valves, antiphospholipid antibody syndrome, smoking, atrial fibrillation, pregnancy and postpartum, oral contraceptives (especially in smokers).

Thrombi and Emboli

Thrombi: Blood clots in blood vessels.
Types: Arterial thrombosis (e.g., from endothelial injury or turbulent flow), venous thrombosis (often due to stasis).
Emboli: Circulating foreign materials that block blood vessels.
Types: Thromboemboli.

Infarct

Infarct: Ischemic necrosis due to blocked blood supply.
Types: White infarct (arterial blockage, pale) and red infarct (venous blockage, hemorrhagic).
Determining factors affect outcome include vascular anatomy, rate of occlusion, collateral circulation, and tissue vulnerability.

Factor V Leiden

Autosomal dominant genetic condition associated with a higher risk of deep vein thrombosis (DVT) and pulmonary embolism (PE).

Two Clinically Important Conditions

Heparin-induced thrombocytopenia (HIT): Autoantibody-mediated platelet activation, aggregation, and consumption, leading to a prothrombotic state.
Disseminated intravascular coagulation (DIC): Widespread clotting in the microcirculation associated with activation of fibrinolysis mechanisms, leading to profuse bleeding.

Shock

A life-threatening condition characterized by inadequate tissue perfusion.
Types: Cardiogenic, hypovolemic, and septic shock.
Mechanisms vary, but they all lead to insufficient blood delivery to tissues.

Stages of Shock

Nonprogressive: Compensatory mechanisms maintain vital organ perfusion.
Progressive: Hypoperfusion leads to worsening metabolic abnormalities (e.g., acidosis).
Irreversible: Cellular and tissue damage is too extensive to recover.

Clinical Manifestations of Shock

Prognosis depends on cause and response to treatment.
Symptoms may include hypotension, weak pulse, tachypnea, altered mental status, cool clammy skin, etc.

Normal Blood Vessels

Arteries have thicker walls with more smooth muscle.
Veins have valves to prevent backflow.
Organized into 3 layers: Intima, Media, Adventitia.

The Main Forms of Vascular Disease

1. Obstruction (Clogging)
1. Weakening (Weakening)
1. Conditionally (Pre-existing)

Congenital Anomalies of Vasculature

Berry aneurysms: Cerebral vessel dilations.
Arteriovenous fistulas: Abnormal connections between arteries and veins.
Fibromuscular dysplasia: Irregular thickening of arteries.

Arteriosclerosis

Hardening of arteries due to arterial wall thickening and loss of elasticity.
Patterns: Arteriosclerosis, Mönckeberg medial calcific sclerosis, and Fibromuscular intimal hyperplasia.

Atherosclerosis

Characterized by atheromas (lipid-filled plaques) that narrow artery lumens.
Types of plaques: Vulnerable, Stable.
Locations prone to atherosclerosis: Generalized, cerebral, coronary, aortic.

Atherosclerosis → Aneurysm

Atherosclerosis weakens arterial walls, leading to aneurysm formation.
Rupture risk is increased as the aneurysm grows and weakens the vessel wall.

Types of Aneurysms

True: Saccular (focal bulge) or fusiform (circumferential dilation).
False (Pseudoaneurysm): Vessel wall is ruptured and blood collects outside the vessel.
Dissection: Blood dissects between the arterial layers, creating a blood-filled channel.

AAA (Abdominal Aortic Aneurysm)

Clinical consequences of AAA include obstruction of branch vessels, compression of adjacent structures, abdominal mass and potentially fatal rupture into the peritoneal cavity.

Aortic Dissection

Aortic dissection: Blood separates the layers of the aorta's wall, creating a blood-filled channel.
Hypertension is a major risk factor.
Consequences include massive hemorrhage, pericardial/pleural/peritoneal rupture.

Marfan Syndrome

A genetic disorder affecting connective tissue due to fibrillin 1 mutation.
Major cardiovascular effect: Weakened aorta, aneurysm risk, potentially fatal.