Lecture 7 and 8 Hemodynamic Disorders I and II

Hemodynamic Disorders

• Disorders of hemodynamics include edema, congestion, and shock.
• Hemostasis includes hemorrhage and thrombosis.

Body Fluids and Compartments

• The body is 60% water
• Two thirds of body water is intracellular.
• The remainder is extracellular, with the interstitium (3rd space) lying between cells.
• Blood plasma contains 5% of total body water.

Edema

• Edema is caused by an increase in interstitial fluid.
• Conditions resulting in increased interstitial fluid can result in Edema.
• Increased capillary pressure (hydrostatic) can lead to impaired venous return and congestive heart failure and can result in Edema.
• Diminished colloid osmotic pressure can be caused by liver disease, kidney disease, and malnutrition, it also results in Edema.

Transudate vs. Exudate

• Transudate is caused by increased hydrostatic pressure or reduced plasma protein; transudate is Protein-poor fluid caused by Heart failure, renal failure, and hepatic failure.
• Exudate is Protein-rich fluid that results in increased vascular permeability it is Inflammatory.

Role of lymphatics

• Removes excess extravascular volume
• Returns it via the thoracic duct
• If capacity for lymphatic drainage is exceeded that is caused Edema.
• Lymphatic fluid flows from the periphery back to the heart.

Lymphatic Obstruction

• Causes impaired clearance of interstitial fluid and can be caused by trauma, invasive tumors, and infectious agents.
• Consequence of Lymphatic Obstruction is Lymphedema in affected part of the body.

Causes of Edema

• Increased hydrostatic pressure can be local or systemic.
• Local causes include mechanical obstruction to venous drainage.
• Systemic causes include cardiac failure that results in increased venous pressure, and renal retention of Na+ and water.
• Decreased osmotic pressure of plasma can be caused by inadequate protein intake (malnutrition, starvation, malabsorption syndrome), excessive loss (nephrotic syndrome), reduced synthesis (liver disease) and lymphatic obstruction (localized lymphedema)

Edema Types

• Cardiac edema is dependent, causing pitting depressions.
• Renal edema leads to Na+ and H2O retention and generalized or periorbital edema.
• Pulmonary edema can be caused by LV failure, renal failure, or bacterial lung infection.
• Cerebral edema can stem from meningitis or encephalitis.

Cerebral Edema

• Trauma or infection can cause cerebral edema
• Cerebral Edema can cause Distended gyri and Narrow sulci

Hyperemia

• Arteriolar dilation leads to increased blood flow.
• Inflammation, or skeletal muscle during exercise are common causes.
• Affected tissues become erythematous which is secondary to engorgement of vessels with oxygenated blood.

Congestion

• Caused by reduced outflow of blood from a tissue
• Congestion can cause edema, lack of blood flow, and chronic hypoxia, leading to ischemic tissue injury and scarring.
• Congestion can also lead to capillary rupture, catabolism of extravasated RBCs, and hemosiderin-laden macrophages.
• Pulmonary congestion can be caused from heart failure.
• One form of Hepatic Congestion is Nutmeg Liver.

Hemorrhage

• Extravasation of blood into the extravascular space, either traumatic or non-traumatic

Distinct Patterns of Hemorrhage

• Hematoma, Petechiae, Purpura and Ecchymoses are types of Hemmorages.
• Blood can accumulate in a body cavity : Hemothorax, Hemopericardium, Hemoperitoneum, Hemarthrosis and Hematuria.

Normal Hemostasis

• It is a Sequence of events at sites of vascular injury, and involves :-Vascular wall, Platelets, and Coagulation cascade
• Vascular Morphology are Intima, Media, Adventitia.
• Vascular Injury leads to Vasoconstriction, Primary Hemostasis and Secondary Hemostasis plus AntiThrombotic Events.

• vWF stimulates platelet adhesion to subendothelial collagen via Gplb receptors on platelets.
• Platelet to Platelet Adherence is Mediated by fibrinogen via GpII/IIIa receptors
• In Normal Hemostasis Vascular injury, Arteriolar vasoconstriction, Subendothelial ECM exposes, Platelets adhere and is activated Tissue factor is exposed, initiates coagulation cascade, Thrombin generates and cleaves fibrinogen into insoluble fibrin and Fibrin meshwork then creates a plug.

Prothrombotic Properties

• Platelets adhere Mediated by von Willebrand factor, Cofactor for platelet binding to matrix elements & Gplb/Gpllb-Illa receptors
• Tissue factor is synthesized by endothelial cells and stimulated by IL-1, TNF, bacterial endotoxins (sepsis)
• Limits hemostatic plug by endothelial cells and tissue plasminogen activator (t-PA).

Actions of Thrombin (FII)

• Platelet aggregation.
• Endothelial activation.
• Lymphocyte activation.
• Monocyte activation.
• Fibrin formation.

Clinical Pathology Lab

• Light Blue-Top Tube (Sodium Citrate) for Laboratory Assessment of Coagulation Cascade.
• Lavender-Top Tube (EDTA).

Normal Hemostasis: Extrinsic Pathway

• The Extrinsic Pathway Coagulation cascade to the Clinical Pathology Lab
• Prothrombin time (PT) is a factor which assesses function of FVII, X, II, V, and fibrinogen (2 5 7 10 fibrinogen)

Normal Hemostasis: Intrinsic Pathway

• Intrinsic Pathway Coagulation Cascade to Clinical Pathology Lab
• Assesses function of FXII, XI , IXmVIII (8 9 11 12) this is known was Partial thromboplastin time (PTT)

Vitamin K and Normal Hemostasis

• Vit K dependent factors: Factors II, VII, IX, X.
• Vitamin K cofactor in glutamic acid residue carboxylation is necessary for calcium binding.
• Vit K is Antagonized by coumadin.
• Proteins C and S dependent Vitamin K that Inactivates factors Va and VIIla.

Thrombosis Inhibitors (Clot Control) in Normal Hemostasis

• Antithrombin III inhibits thrombin in various forms and Proteins C and S Inactivates factors Va and VIIla.
• Fibrinolysis or restricting Coagulation happens with : plasmin, it Breaks down fibrin preventing polymerization, as well we see-Fibrin split products (FSPs) and D-dimers.
• The body restricts fibrinolysis in order to maintain normal hemostasis with Plasmin.

Restricting Coagulation : Fibrinolysis

• Elevated levels of FD/SPs and D-dimers, Disseminated intravascular coagulation (DIC), Deep vein thrombosis (DVT) and Pulmonary embolism (PE) happens in Restricting Coagulation in Fibrinolysis

Abnormalities Associated with Thrombosis

• Endothelial Injury or Alterations in Blood Flow, cause Turbulence
• Alterations in Blood Flow such as Valular vegetations, Atherosclerotic plaques Aneurysms, Hypertension

Factors Promoting Thrombosis

• Turbulence causes Endothelial cell injury, Valular vegetations Atherosclerotic plaques Aneurysms and Hypertension.
• Interruption of Laminar Flow (Stasis due to Heart failure, vascular obstruction) : Promotes endothelial cell activation, Concentrates coagulation factors & ↑Platelet contact to endothelium.

Hypercoagulability

• Disorders associated with hypercoagulability of the blood can be primary (genetic) or secondary (acquired) conditions.
• Factor V mutation (Leiden mutation) is a Primary (Genetic) Disorders, and the Mutation renders factor V resistant to cleavage.
• Mutations in prothrombin gene are Primary (Genetic) Disorders
• Elevations of Homocysteine are Primary (Genetic) Disorders.
• Heparin-induced thrombocytopenia (HIT) syndrome is considered a disorder that is Secondary (Acquired) which results by Heparin induced Ab synthesis against platelets
• Antiphospholipid Antibody Syndrome disorder that is Secondary (Acquired) activates platelets by binding specific antibodies.
  • This sometimes demonstrates as Paradox Promotes thrombosis in vivo and Prolongs clotting time (PPT) in vitro

Antiphospholipid Antibody Syndrome

• Clinical Presentations of Antiphospholipid Antibody Syndrome include: Recurrent thromboses, Repeated miscarriages, Cardiac valve vegetations, Thrombocytopenia & Pulmonary embolism.
• Oral Contraceptives,↑ Synthesis of Coagulation Factors, Anticoagulant Synthesis

Hypercoagulability from Cancer

• Cancers cause Release of procoagulant tumor products.

Characteristics of Thrombi

• Arterial thrombi or cardiac thrombi form at sites of turbulence or endothelial injury and grows in retrograde fashion.
• Venous thrombi form at sites of stasis and Extend in the direction of blood flow.
• Thrombi can embolize (Thromboemboli).

Morphology of Thrombi

• Contain Laminations of lines of Zahn
• Arterial thrombi are occlusive with an alternating platelet and fibrin / RBCs composition, and are known as lines of Zahn
• Venous thrombosis (Phlebothrombosis) are red(stasis thrombi, and Veins of the lower extremities most commonly are involved.

Dynamic Changes involving Thrombi

• Propagation, Embolization, Dissolution & Organization and recanalization

Clinical Consequences of Thrombi

• Venous Thrombosis :- Saphenous veins stasis and Deep veins thrombosis
• Venous Thrombosis associations :-Hypercoagulable States , CHF , Surgery, Trauma, &Pregnancy.
• Tumor-associated antigens can cause Migratory thrombophlebitis or Trousseau syndrome.
• Arterial and Cardiac Thrombosis results usually from Atherosclerosis / Endothelial injury.
• Cardiac mural thrombi post- MI, Aortic / mural thrombi can embolize
• Aortic thrombi effect distal organs and tissues.

Disseminated Intravascular Coagulation (DIC)

• Characteristics :-Widespread fibrin thrombi in the microcirculation (widespread activation of thrombin), Widespread microvascular thrombosis, Platelet and coagulation protein consumption, Activation of fibrinolytic pathways & Bleeding catastrophe.

Conditions Precipitating DIC

• Obstetric complications, Advanced malignancy, Massive trauma, Septic and Burns

Laboratory Diagnosis of DIC

• Fibrin degradation / split products.
• (D-dimers) levels.
• Fragmented RBCs on blood smear are also known as shistocytes.
• Prolonged Bleeding Time and Prothrombin Time.
• ↓ Fibrinogen & ↓ Platelets
• ↑ FDPs.

Embolism

• May be intravascular and comprised of solid, liquid, gas, or silicone.
• Carried from point A → B, distant from the point of origin.
• Vessel caliber accommodation is necessary otherwise you are doomed!

Pulmonary Emboli

• Originate from leg DVTs (deep vein thrombosis) and lead to saddle embolus or sudden death.
• Small / Medium size Emboli may be clinically silent or may cause chest pain, hemoptysis, chronic cor pulmonale and pulmonary hypertension (PHT).
• Homans Sign could show venous congestion.
• Large emboli block bifurcation of pulmonary artery, causing the Saddle Embolus + Right heart failure.

Systemic Thromboemboli

• Emboli of Arterial Origin include :-Intracardiac mural thrombi; Left ventricular wall infarcts; Left atrial dilation and fibrillation; Aortic aneurysms; Ulcerated atherosclerotic plaques; Valvular vegetation & Paradoxical emboli.

Systemic Thromboemboli ( Venous Emboli)

• Fat and Marrow Embolism.
• Air / Gas Embolism.
• Amniotic Fluid Embolism.
• Silicone Embolism.

Infarction

• It is an Area of Ischemic Necrosis
• This is the result of Vascular occlusion by arteries and veins

Factors That Influence Infarct Development

• The vessel composition, Occlusion degree, hypoxic tolerability, and O2 content in blood.

Infarction Targets

• Heart.
• Brain.
• Lungs.
• GI / SLI.
• Distal extremities.

Morphology of Infarcts : Red Infarcts

• Occur with venous occlusions as in testicular torsion.
• Loose, spongy tissues, eg lung, where blood can collect in the infarcted zone.
• Tissues with dual circulations as in the lung and small intestine that allow blood to flow from an unobstructed parallel supply into a necrotic zone)
• Tissues previously congested by sluggish venous outflow.

Morphology of Infarcts: White Infarcts

• Originate with arterial occlusions in solid organs - heart, spleen,kidney
• Tissue density limits seepage of blood from adjoining capillary beds into the necrotic area.
• Ischemic coagulative necrosis : replaced by scar
• Liquefactive necrosis : Cystic cavity remains