Term for the accumulation of fluid in tissues, resulting from a net movement of water into extravascular spaces
What is edema? (Fluid in body cavities is an effusion.)
This is the active process in which arteriolar dilation increases blood flow, turning tissues red (erythema).
What is hyperemia?
Define hemostasis.
The process by which blood clots form at sites of vascular injury.
Name the three components of the triad that underlies thrombosis. (Also known as Avery's triad of thrombosis)
Virchow triad: (1) endothelial injury, (2) stasis or turbulent blood flow, (3) hypercoagulability of the blood
Define shock.
A state of circulatory failure that impairs tissue perfusion and leads to cellular hypoxia — initially reversible, but prolonged shock leads to irreversible tissue injury and can be fatal.
Name the two opposing pressures whose balance normally keeps tissues "dry" — one pushes fluid out of capillaries, the other pulls it back in.
What are vascular hydrostatic pressure and plasma colloid osmotic pressure? 
This is the passive process resulting from reduced venous outflow, giving tissues an abnormal blue-red color.
What is congestion?
Abnormal bleeding stems from defects in one of three things. Name them.
Vessel walls, platelets, or coagulation factors (all must function properly to ensure hemostasis).
Define an embolus.
Name types of emboli.
A detached intravascular solid, liquid, or gaseous mass carried by the blood from its point of origin to a distant site, where it often obstructs flow and causes tissue dysfunction or infarction.
Fat embolism, air embolism, thromboembolism, amniotic fluid embolism
Which colour infarct occurs with venous occlusion, and which with arterial occlusion in compact tissues?
Venous occlusion (or spongy tissue with dual blood supply where blood can collect) → hemorrhagic (red); arterial occlusion in compact tissue → pale (white).
A patient with nephrotic syndrome develops edema. Which of the five mechanisms of edema is at work, and how?
Decreased colloid osmotic pressure from increased loss of plasma albumin. (Other causes of reduced albumin: decreased synthesis in liver disease/protein malnutrition.)
Name the secondary (acquired) hypercoagulable risk factors.
Secondary (Acquired)
Strong Risk Factors for Thrombosis
• Prolonged bed rest or immobilization
• Myocardial infarction
• Atrial fibrillation
• Tissue injury (surgery, fracture, burn)
• Cancer
• Prosthetic cardiac valves
• Disseminated intravascular coagulation
• Heparin-induced thrombocytopenia
• Antiphospholipid antibody syndrome
Other Risk Factors for Thrombosis
• Cardiomyopathy
• Nephrotic syndrome
• Hyperestrogenic states (pregnancy and postpartum)
• Oral contraceptive use
• Sickle cell anemia
• Smoking
A patient has minute 1- to 2-mm skin/mucosal hemorrhages. Name this finding and state whether it reflects a defect of primary or secondary hemostasis.
Petechiae — a defect of primary hemostasis (platelet defects or von Willebrand disease). Slightly larger lesions (≥3 mm) are purpura.
Why are aspirin and other platelet inhibitors useful in coronary artery disease and acute MI? Base your answer on where platelet activation matters.
Endothelial injury leading to platelet activation almost inevitably underlies thrombus formation in the heart and arterial circulation, where high blood flow rates impede clot formation; cardiac and arterial clots are typically platelet-rich, and platelet adherence/activation is a necessary prerequisite under high shear stress.
Name the four factors that determine whether vascular occlusion actually causes infarction.
(1) Collateral blood supply, (2) the rate at which the obstruction develops, (3) intrinsic tissue susceptibility to ischemic injury, (4) blood oxygenation
Edema fluid may be protein-poor or protein-rich. Give the correct term for each and one example of each cause.
Transudate = protein-poor; exudate = protein-rich. Classic causes: increased hydrostatic pressure or reduced osmotic pressure (transudate) vs. increased vascular permeability, e.g., inflammation (exudate).
Explain the "nutmeg liver" — what is the gross pattern, and what is happening microscopically?
Chronic passive congestion of the liver: central areas are red and slightly depressed against surrounding tan viable parenchyma (resembling a cut nutmeg).
Microscopically: centrilobular congestion and hemorrhage, hemosiderin-laden macrophages, and variable hepatocyte dropout and necrosis.
Name the risk factors of lower extremity DVT
Name the four possible fates of a thrombus.
It may propagate, resolve, organize, or embolize. (Thrombosis injures tissue by local vascular occlusion or distal embolization.)
Propagation. Thrombi accumulate additional platelets and fibrin and enlarge.
Embolization. Thrombi dislodge and travel to other sites in the vasculature.
Dissolution. Dissolution is the result of fibrinolysis, which can lead to the rapid shrinkage and total disappearance of recent thrombi. In contrast, extensive fibrin deposition and cross-linking in older thrombi render them more resistant to lysis. This distinction explains in part why therapeutic administration of fibrinolytic agents such as t-PA (e.g., in the setting of acute coronary thrombosis) is generally effective only when given during the first few hours of a thrombotic event.
Organization and recanalization. Older thrombi become organized by the ingrowth of endothelial cells, smooth muscle cells, and fibroblasts. Capillary channels that reestablish the continuity of the original lumen, albeit to a variable degree, eventually form. Continued recanalization may convert a thrombus into a smaller mass of connective tissue that becomes incorporated into the vessel wall. Eventually, with remodeling and contraction of the mesenchymal elements, only a fibrous lump may remain to mark the original thrombus.
Name and explain the three general categories of shock.
Cardiogenic shock results from low cardiac output due to myocardial pump failure. This can be due to intrinsic myocardial damage (infarction), ventricular arrhythmias, extrinsic compression (cardiac tamponade), or outflow obstruction (e.g., pulmonary embolism).
Hypovolemic shock results from low cardiac output due to low blood volume, such as can occur with massive hemorrhage or fluid loss from severe burns.
Sepsis and septic shock are interrelated and somewhat overlapping conditions:
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection.
Septic shock is defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone.
Systemic inflammatory response syndrome (SIRS) is a sepsis-like condition associated with systemic inflammation that may be triggered by a variety of nonmicrobial insults, such as burns, trauma, and/or pancreatitis.
Less commonly, shock can occur in the setting of a spinal cord injury (neurogenic shock), or an IgE-mediated hypersensitivity reaction (anaphylactic shock). In both these forms of shock, acute vasodilation leads to hypotension and tissue hypoperfusion.
List all five pathophysiologic categories of edema with a representative condition for each.
(1) Increased hydrostatic pressure: Reduced venous return — CHF, ascites/liver cirrhosis AND arteriolar dilation - heat and neurohumoral dysregulation;
(2) Decreased plasma osmotic pressure — liver disease, protein malnutrition, nephrotic syndrome;
(3) Lymphatic obstruction — inflammation, neoplastic, postsurgical, postirradiation;
(4) Sodium and water retention — excessive salt intake with renal insufficiency and increased tubular reabsorption of sodium (renal hypoperfusion and increased renin-angiotensin-aldosterone secretion)
(5) Inflammation - Acute, chronic, angiogenesis
Primary (Genetic)
Common
• Factor V mutation: factor V Leiden (Arg to Gln substitution in amino acid residue 506 leading to resistance to activated protein C)
• Prothrombin mutation (G20210A noncoding sequence variant leading to increased prothrombin levels)
• Increased levels of factors VIII, IX, XI, or fibrinogen (genetics unknown)
Rare
• Antithrombin III deficiency
• Protein C deficiency
• Protein S deficiency
Very Rare
• Fibrinolysis defects
• Homozygous homocystinuria (deficiency of cystathione β-synthetase)
Contrast the bleeding pattern of defects of primary vs. secondary hemostasis.
Primary (platelets/vWD): small bleeds in skin or mucous membranes — petechiae, purpura, epistaxis, GI bleeding, menorrhagia.
Secondary (coagulation factors, e.g., hemophilia): bleeds into soft tissues (muscle) or joints (hemarthrosis).
Define DIC, explain the paradox of its clinical course, and give its synonym.
DIC = widespread thrombosis within the microcirculation, a complication of many conditions with systemic activation of thrombin (obstetric complications to advanced malignancy). Microvascular thrombi cause diffuse circulatory insufficiency and organ dysfunction (brain, lungs, heart, kidneys).
Paradox: runaway thrombosis "uses up" platelets and coagulation factors (hence consumptive coagulopathy) and often activates fibrinolysis — so symptoms of thrombosis can evolve into a bleeding catastrophe, e.g., hemorrhagic stroke or hypovolemic shock.
Name and explain the three stages of shock