Medical

9. Active hyperemia versus congestion (passive hyperemia)

a. Definition: an excessive amount of blood in a tissue or organ secondary to vasodilatation (active) or diminished venous outflow (passive)

Table 5-1. Properties of Active Hyperemia and Congestion (Passive Hyperemia)

n

Active Hyperemia

Congestion (Passive Hyperemia) j

Type

Active process

Passive process

Mechanism

Vasodilatation mediated by

■ Vasoactive mediators

■ Neurogenic reflexes

Decreased venous outflow

Examples

Inflammation

CHF

Exercise

DVT

Blushing

Budd-Chiari syndrome

B. Hemostasis and Bleeding Disorders

1. Hemostasis a. Definition: sequence of events leading to the cessation of bleeding by the formation of a stable fibrin-platelet hemostatic plug b. Hemostasis involves i. The vascular wall ii. Platelets iii. Coagulation system

2. Vascular wall injury a. Transient vasoconstriction is mediated by endothelin b. Thrombogenic factors i. Changes in blood flow cause turbulence and stasis, which favors clot formation ii. Release of tissue factor from injured cells activates Factor VII (extrinsic pathway)

iii. Exposure of thrombogenic subendothelial collagen activates Factor XII (intrinsic pathway)

iv. Release of von Willebrand factor (vWF), which binds to exposed collagen and facilitates platelet adhesion v. Decreased endothelial synthesis of antithrombogenic substances (prostacyclin, nitric oxide [N02], tissue plasminogin activator, and thrombomodulin)

3. Platelets a. Derived from megakaryocytes in the bone marrow b. Step 1: platelet adhesion i. First vWF adheres to subendothelial collagen ii. Platelets then adhere to vWF by glycoprotein lb c. Step 2: platelet activation i. Platelets undergo a shape change and degranulation occurs

Table 5-2. Contents of Platelet Alpha Granules and Dense Bodies

Alpha Granules

Dense Bodies

Fibrinogen

ADP (potent platelet aggregator)

Fib rone din

Calcium

Factor V and vWF

Histamine and serotonin

Platelet factor 4

Epinephrine

Platelet-derived growth factor (PDGF)

ii. Platelet synthesis of thromboxane A2

iii. Membrane expression of the phospholipid complex, which is an important platform for the coagulation cascade d. Step 3: platelet aggregation i. Additional platelets are recruited from the blood stream ii. ADP and thromboxane A2 are potent mediators of aggregation iii. Platelets bind to each other by binding to fibrinogen using Gp Ilb-IIIa e. Laboratory tests for platelets i. Platelet count (normal 150 to 400 K)

ii. Bleeding time test (normal 2 to 7 minutes)

iii. Platelet aggregometry

Table 5-3. Common Platelet Disorders

Thromb o cytopenia

Qualitative Defects

Decreased production

von Willebrand disease

Aplastic anemia (drugs, virus, etc.)

Bernard-Soulier syndrome

Tumor

Glanzmann thrombasthenia

Drugs (aspirin)

Uremia

Increased destruction

Immune thrombocytopenia (ITP)

Thrombotic thrombocytopenia purpura (TTP)

Disseminated intravascular coagulation (DIC)

Hypersplenism

4. Immune thrombocytopenia purpura (ITP)

a. Etiology i. Antiplatelet antibodies against platelet antigens such as Gp Ilb-IIIa and Gp Ib-IX

ii. Antibodies are made in the spleen iii. Platelets are destroyed peripherally in the spleen by macrophages, which have Fc receptors that bind IgG-coated platelets b. Forms of ITP

i. Acute ITP

■ Seen in children following a viral infection

• Self-limited disorder ii. Chronic ITP

• Usually seen in women in their childbearing years

• May be the first manifestation of systemic lupus erythematosus (SLE)

• Petechiae, ecchymoses, menorrhagia, and nosebleeds c. Lab i. Decreased platelet count and prolonged bleeding time ii. Normal prothrombin time (PT) and partial thromboplastin time (PTT)

iii. Peripheral blood smear shows thrombocytopenia with enlarged immature platelets (megathrombocytes)

iv. Bone marrow biopsy shows increased numbers of megakaryocytes with immature forms d. Treatment i. Corticosteroids, which decrease antibody production ii. Immunoglobulin therapy, which floods Fc receptors on splenic macrophages iii. Splenectomy, which removes the site of platelet destruction and antibody production

Thrombotic thrombocytopenic purpura (TTP)

a. Pathology i. Widespread formation of platelet thrombi with scant fibrin (hyaline thrombi)

ii. No activation of the coagulation system b. Clinical findings i. Most often affects adult women ii. Pentad of characteristic signs

■ Thrombocytopenia

• Microangiopathic hemolytic anemia

• Neurologic symptoms

■ Renal failure c. Lab i. Decreased platelet count and prolonged bleeding time ii. Normal PT and PTT

iii. Peripheral blood smear shows thrombocytopenia and schistocytes, and reticulocytes is d. Hemolytic uremic syndrome (HUS)

i. Occurs most commonly in children ii. Follows a gastroenteritis with bloody diarrhea iii. Organism: verotoxin-producing E. coli 0157:H7

iv. Similar clinical pentad

c. Extrinsic coagulation pathway is activated by the release of tissue factor d. Laboratory tests for coagulation i. Prothrombin time (PT)

■ Tests the extrinsic and common coagulation pathways

■ VII, X, V, prothrombin, fibrinogen ii. Partial thromboplastin time (PTT)

■ Tests the intrinsic and common coagulation pathways • XII, XI, IX, VIII, X, V, prothrombin, fibrinogen iii. Thrombin time (TT) tests for adequate fibrinogen levels iv. Fibrin degradation products (FDP) tests the fibrinolytic system (increased with DIC)

7. Hemophilia A (classic hemophilia)

a. Deficiency of factor VIII

b. X-linked recessive c. Clinical features i. Predominately affects males ii. Symptoms are variable dependent on the degree of deficiency iii. Spontaneous hemorrhages into joints (hemarthrosis)

iv. Easy bruising and hematoma formation after minor trauma v. Severe prolonged bleeding after surgery or lacerations vi. No petechiae or ecchymoses d. Lab i. Normal platelet count and bleeding time ii. Normal PT and prolonged PTT

e. Treatment: factor VIII concentrate

8. Hemophilia B (Christmas disease)

a. Deficiency of factor IX

b. X-linked recessive c. Clinically identical to hemophilia A

9. Acquired coagulopathies a. Vitamin K deficiency: decreased synthesis of factors II, VII, IX, X, and protein C & S

b. Liver disease: decreased synthesis of virtually all clotting factors 10. Von Willebrand disease a. Definition: inherited bleeding disorder characterized by either a deficiency or qualitative defect in von Willebrand factor b. vWF is normally produced by endothelial cells and megakaryocytes c. Clinical features i. Spontaneous bleeding from mucous membranes ii. Prolonged bleeding from wounds iii. Menorrhagia in young females iv. Bleeding into joints is uncommon d. Lab i. Normal platelet count and a prolonged bleeding time ii. Normal PT with often a prolonged PTT

iii. Abnormal platelet response to ristocetin (adhesion defect) is an important diagnostic test iv. Treatment: treat mild cases (type I) with desmopressin (an antidiuretic hormone [ADH] analog), which releases vWF from Weibel Palade bodies of endothelial cells

11. Disseminated intravascular coagulation (DIC)

a. DIC is always secondary to another disorder b. Causes i. Obstetric complications (placental tissue factor activates clotting)

ii. AML M3 (cytoplasmic granules in neoplastic promyelocytes activate clotting)

iii. Adenocarcinomas (mucin activates clotting)

iv. Gram-negative sepsis (tumor necrosis factor [TNF] activates clotting)

v. Micro-organisms (especially meningococcus and rickettsia)

c. Pathology i. Results in widespread microthrombi ii. Consumption of platelets and clotting factors causes hemorrhages d. Lab i. Platelet count is decreased ii. Prolonged PT/PTT

iii. Decreased fibrinogen iv. Elevated fibrin split products (D-dimers)

e. Treatment: treat the underlying disorder C. Thrombosis

1. General a. Definition: pathologic formation of an intravascular fibrin-platelet thrombus b. Factors involved in thrombus formation (Virchow's Triad)

i. Endothelial injury

• Atherosclerosis

• Vasculitis

• Many others ii. Alterations in laminar blood flow

• Hyperviscosity of blood (e.g., polycythemia vera)

iii. Hypercoaguability of blood

• Clotting disorders (factor 5 leiden, deficiency of antithrombin III, protein C, or protein S)

• Tissue injury (postoperative and trauma)

■ Nephrotic syndrome

• Oral contraceptives

Table 5-4. Comparison of a Thrombus with a Blood Clot

Thrombus

Blood Clot

Location

Intravascular

Extravascular or intravascular

(postmortem)

Composition

Platelets Fibrin

RBCs and WBCs

Lacks platelets Fibrin

RBCs and WBCs

Lines of Zahn

Present

Absent

Shape

Has shape

Lacks shape

c. Common locations of thrombus formation i. Coronary and cerebral arteries ii. Heart chambers atrial fibrillation or post-MI (mural thrombi)

iii. Aortic aneurysms iv. Heart valves (vegetations)

v. Deep leg veins (DVTs)

d. Outcomes of thrombosis i. Vascular occlusion and infarction ii. Embolism iii. Thrombolysis iv. Organization and recanilization D. Embolism

1. Definition: any intravascular mass that has been carried down the bloodstream from its site of origin, resulting in the occlusion of a vessel

2. Composition of emboli a. Thromboemboli—most common (98%)

b. Atheromatous emboli—severe atheroscerosi c. Fat emboli—bone fractures and soft-tissue trauma d. Bone marrow emboli—bone fractures and cardiopulmonary resuscitation (CPR)

e. Gas emboli—decompression sickness ("the bends" and Caisson disease)

f. Amniotic fluid emboli—complication of labor g. Tumor emboli—metastasis h. Talc emboli—intravenous drug abuse (IVDA)

i. Bacterial/septic emboli—infectious endocarditis

3. Pulmonary emboli (PE) a. Epidemiology i. Often clinically silent ii. Most commonly missed diagnosis in hospitalized patients iii. Found in almost half of all hospital autopsies b. Pathology i. Most (95%) arise in deep kg veins (DVT)

ii. Pelvic venous plexuses of the prostate and uterus iii. Right side of the heart c. Diagnosis i. V/Q scan mismatch ii. Doppler ultrasound of the leg veins to detect a DVT

d. Potential outcomes of PEs i. No sequela (75%)

■ Asymptomatic or transient dyspnea/tachypnea

• No infarction (dual blood supply)

• Complete resolution ii. Infarction (15%)

• More common in patients with cardiopulmonary compromise

■ Shortness of breath (SOB), hemoptysis, pleuritic chest pain, pleural effusion

■ Gross: hemorrhagic wedge-shaped infarct

• Regeneration or scar formation iii. Sudden death (5%)

• Large emboli may lodge in the bifurcation (saddle embolus) or large pulmonary artery branches and cause sudden death

■ Obstruction of >50% of the pulmonary circulation iv. Chronic pulmonary hypertension (3%)

• Caused by recurrent PEs

• Increased pulmonary resistance

• Pulmonary hypertension

• May lead to cor pulmonale 4. Systemic arterial emboli a. Most arise in the heart b. Most cause infarction c. Common sites of infarction i. Lower extremities ii. Brain iii. Intestine iv. Kidney v. Spleen d. Paradoxical emboli i. Definition: any venous embolus that gains access to the systemic circulation by crossing over from the right to the left side of the heart through a septal defect

E. Infarction

1. Infarction a. Definition: localized area of necrosis secondary to ischemia b. Pathogenesis i. Most infarcts (99%) result from thrombotic or embolic occlusion of an artery or vein

Bridge to Anatomy

The dual blood supply to the lungs is from the pulmonary artery and the bronchial arteries.

Clinical Correlate

4. • w-jya-c >■>»-;; - - -J -S.»-- -».5VX.- — 7 si

The classic presentation of massive PE is an intensive care unit (ICU), postoperative, or bed-ridden patient who gets out of bed and collapses.

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