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Flashcards in Pathology: abnormalities of blood supply Deck (41):

Localized edema vs. systemic edema

-Localized: local disturbance of fluid exchange of a tissue. Results from: inflammation, allergic rxn, venous obstruction, lymphatic obstruction
-Localized edema can lead to non-pitting
-Systemic edema: increased retention of total body Na/water. Results from CHF, renal disease (protein loss-> proteinuria), decreased protein synthesis in liver (cirrhosis), malnutrition
-Systemic edema can lead to subcutaneous pitting


Transudate vs. exudate

-Transudate: noninflammatory edema due to increased hydrostatic pressure, decreased oncotic pressure, or lymphatic obstruction (no change in vascular permeability)
-Sp. Grav 1.015


Hyperemia and congestion

-Hyperemia (redness) due to arteriolar vasodilation, leads to more blood flow (can be from inflammation, exercise)
-Congestion (cyanosis) due to impaired venous outflow. May be local (obstructed veins) or general (CHF)
-Blood looks blue due to deoxygenation. If chronic may lead to necrosis via hypoxia


Pulmonary edema

-Acute: due to sudden left ventricular failure (left-sided HF, MI) causing increased hydrostatic pressure (transudate)
-Transudate forms in interstitium within alveoli, eventually spills into airways
-Capillaries my rupture (hemorrhage)
-Chronic: persistent milder hydrostatic pressure increase. Alveoli respond by developing thick, fibrotic septae
-Airspaces may contain macrophages w/ hemosiderin (heart failure cells)
-If there is massive infiltration by leukocytes it is pneumonia (causes exudate)


Liver congestion

-Acute: may be secondary to shock or hepatic vein thrombosis. Central vein and sinusoids are distended w/ blood
-Centrolobular hepatocytes more vulnerable to hypoxic injury
-Chronic: due to right sided (ventricular) HF, obstruction of venous outflow. Causes centrilobular congestion (nutmeg liver)
-Centrilobular hepatocytes often atrophy and necrose, focal hemorrhages may be seen
-Periportal hepatocytes not affected, mid-lobular may have fatty change


Centrilobular fibrosis

-Due to chronic centrilobular congestion
-Centrilobules will become hypoxic, resulting in infarct and coagulative necrosis, inflammation, scarring
-Scar in middle of centrilobe (where vein used to be) surrounded by unhealthy hepatocytes
-Cirrhosis: normal hepatocytes surrounded by fibrosis (from alcoholism or hepatitis (not A), but not from centrilobular congestion
-Can distinguish btwn arterial obstruction and venous obstruction by presence of RBCs (color of tissue)
-If the middle is hepatocytes, and the outside is scar then it is cirrhosis (usually alcoholism)



-Arrest in blood flow (usually due to thrombosis, embolism, atherosclerosis, vascular spasms at site of injury)
-Depends on 3 components: injured vessel wall, platelets, coagulation cascade
-Vessel walls (endothelial cells, ECs) are anticoagulant, when injured they become procoagulant
-Exposure to subendothelial collagen leads to platelet binding and activation. Platelets adhere to form primary platelet plug. Coagulation cascade begins
-Coagulation cascade: 7 steps but last 2 steps are most critical. Prothrombin is converted to thrombin, which cleaves fibrinogen into fibrin (insoluble) which creates mesh within platelet plug (definitive platelet plug)


Factors of hemostasis

-Hemostasis is a balance btwn 3 pathways: coagulation, fibrinolytic (contains coagulation), and anticoagulation (regulates actions btwn coagulation and fibrinolytic pathways)



-Escape of RBCs across intact vessels or from vascular rupture (can lead to shock)
-Can be secondary to congestion and increased hydrostatic pressure
-Other causes: bleeding disorders (coagulopathy), abnormalities in coagulation, fragile vessels
-Also trauma: atherosclerosis, aneurysms, inflammation, erosion by tumors
-Extensive hemorrhage cal lead to jaundice



-Type of hemorrhage, localized blood within tissue
-Petechiae: smallest (pin point)
-Purpura: slightly larger
-Eccymoses: subcutaneous (bruises)
-Large accumulations (hemothorax)



-Due to dysregulation or imbalance btwn pro and anti coagulation
-Not the same as blood clot
-Thrombosis is result of coagulation cascade and platelet activation within CVS of living person. Blood clots from coagulation cascade only and develops in extravascular space after blood is spilled over
-Thrombosis is often attached to underlying ECs, displays orderly layering of platelets, RBCs, fibrin. Blood clots are not attached to underlying ECs, display random ordering of RBCs and fibrin


Causes of thrombosis

-Virchow's triad: EC injury, stasis/turbulence of blood, hypercoagulativity
-EC injury exposes subendothelial collagen (ECM) and leads to platelets adherence/aggregation
-EC injury can be due to loss of EC, denudation of EC (atherosclerosis), disturbances of local pro/anti coagulation
-Changes in blood flow (from laminar flow): laminar flow is cells/platelets flow in center of vessel and plasma along periphery
-Deviation form this increases chance that platelets contact underlying vessel wall and thrombus formation
-Hypercoagulativity: alteration in hemostatic regulation that predisposes to thrombus formation (both genetic and acquired)
-Other causes: prolonged immobilization, obesity, smoking, oral contraceptives, cancer, surgery, pregnancy, platelet hyperreacivity, missing natural anticoagulants


Arterial thrombosis

-Usually due to atherosclerosis, turbulence
-Turbulence increases as plaque enlarges
-Turbulence also arises at bifurcations
-Most common sites of arterial thrombosis: coronary, cerebral, femoral arteries
-Thrombi have points of attachment to underlying vessel/surface
-Arterial thrombi grow in retrograde direction (against blood flow) and appear more compact and white (fewer RBCs) b/c they are under higher pressures
-Venous thrombi grow with blood flow, are less compact and often more red (more RBCs) b/c they are formed under lower pressure


Atherogenesis (pt. 1)

-Chronic inflammatory, fibroproliferative process that is a response to damage to ECs
-Causes include: hyperlipidemia (mostly LDL), hypertension (most significant), DM, smoking, genetics, age, obesity, gender, infections
-LDL extravasate through leaky/injured EC to sub endothelial space
-Upon injury, EC activation causes decreased NO secretion, leading to vasoconstriction, and up regulation of adhesion molecules for leukocytes
-This converts anticoagulative surface into a procoagulative one
-In sub endothelial space, LDL is oxidized by macrophages, ECs, platelets or SMCs. Oxidized LDL has pro-atherogenic properties


Atherogenesis (pt. 2)

-Monocytes and T cells migrate across endothelial into intima where they internalize LDL and become foam cells (also SMCs and circulating stem cells)
-Ox-LDL leads to T cell activation, causing release of cytokines and chemokines, perpetuating a chronic inflammatory response and plaque development
-Endothelial dysfunction: reduced NO secretion leads to vasoconstriction. Can also include more adhesion molecules on surface, enhanced permeability, increase in cyto/chemokines
-Fibrous cap: SMCs migrate from media to intima to proliferate and synthesize ECM proteins. Contributes to stability of fibrous cap


Cardiac (mural) thrombi

-Usually not occlusive, may develop due to MI (endocardial damage + inflammation) which results in loss of contractility b/c of fibrosis
-Leads to stasis of blood flow
-Left atrial dilation usually due to chronic mitral (bicuspid) valve stenosis (narrowing of valve) leads to stenosis
-Atrial fibrillation often occurs w/ atrial dilation. Uncoordinated beat does not allow atrium to fully empty into ventricle (more stasis)
Valvular disease: thrombi form on leaflets of valves (vegetations)
-Aortic thrombi are result of atherosclerosis + aneurysm (balloon-like dilation)
-Cardiac and aortic thrombi may contain stripes of red (RBCs, called lines of zahn) and white (flatelets, fibrin, leukocytes), which indicates the thrombus occurred during blood flow (not post-mortem)


Venous thrombosis

-Frequently originate w/in valves as they produce eddies and stagnant blood
-2 types: superficial venous thrombosis (SVT) and deep vein thrombosis (DVT)
-DVTs are prone to embolization but SVTs are not (only DVTs are affected by skeletal muscle contraction)



-Usually occur in saphenous veins of leg (accompanied by varicose- enlargement)
-Can be result of infection, trauma, IV catheters
-Clinical features: localized pain, warmth, hyperemia, edema, tenderness
-Varicose veins form b/c superficial leg veins not dependent on milking action of leg muscles, so gravity is main cause of stasis
-Not prone to embolize



-Occur in deep veins (femoral, popliteal, posterior tibial) in leg
-Highest concern in post-surgicl patients (surgery/hypercoagulability + immobilization)
-May present as distended superficial veins and tenderness, warmth, edema, cyanosis
-Most common complaint is calf pain
-Deep veins are constantly milked by movement of leg muscles, thus immobilization greatly increases chance of DTV (causes stasis)
-Grow in direction of blood flow, and may not be firmly attached to ECs
-Tails are often freely mobile and prone to breaking loose
-Invariably occlusive and may traverse long distances in vessels
-Formed under low pressure and contain more RBCs then arterial thrombi (red thrombi)
-Hemorrhagic infarction can occur when drainage of blood supply is halted due to venous thrombi. Backup of blood can lead to hemorrhage, edema, infarction


Outcome of thrombi

-Formation may be triggered by any of virchows triad (EC injury most important)
-They may propagate, resolve, organize, or embolize
-Propagation: accumulation of more fibrin and gets bigger
-Dissolution: removal of thrombus by fibrinolytic system
-Organization/recanalization: conversation to vascularized mass of scar tissue w/ potential to reestablish blood flow (recanalization requires vessels lined w/ EC)
-Embolization: detachment and transport to a distant site in CVS



-Activation of fibrinolytic system causes fibrin to be broken down by hydrolysis
-Plasmin breaks down the fibrin, but must be activated from its pro-nz form plasminogen
-Tissue plasminogen activator (tPa) and/or streptokinase/urokinase can activate plasminogen


DIC: Disseminated intravascular coagulation

-A burst of systemic coagulation w/ intravascular fibrin deposition
-Arises form some complication of an event triggering generalized coagulation
-Forms extensive micro thrombi and consumes a lot of the total supply of fibrin, platelets, and coagulation factors
-Identify DIC via increase in prothrombin/partial thromboplastin time (thrombocytopenia), positive D-dimer test, anemia
-Depletion in clotting factors plus activation of fibrinolytic system makes patient susceptible to hemorrhage


Causes of DIC

-1) release of thromboplastic substances into circulation, and 2) widespread injury to endothelial cells
-Thromboplastic substances: thromboplastin (tissue-released factor due to injury), endotoxin sepsis, amniotic fluid, premature placental detachment, malignant tumors (pancreas, lung), trauma/necrosis (burns, surgery, brain damage)
-Mechanisms that cause EC injury: trauma, infection, Ag-Ab complexes, temp extremes (burn/frostbite)


Clinical presentation of DIC

-Patients present thrombosis and hemorrhage
-Microthrombi in brain, kidney, heart, lungs mostly, produce microinfarctions
-Cause pulmonary edea and respiratory failure, convulsions and coma, renal failure, circulatory collapse
-May show skin and mucous membrane bleeding, other hemorrhage
-Anemia due to shearing of RBCs as they bass through the fibrin threads of the micro thrombi
-DIC is usually acute (can be low-grade chronic in some cancers)
-Rx is usually heparin (anticoagulant) with procoagulants (platelets, clotting factors)



-Detached mass (solid, liquid, gas) that is carried through CVS until it is lodged in a vessel
-Almost all are from thrombi, other sources: fat, atherosclerosis, bone marrow, amniotic fluid, gas, tumors, parasites, foreign objects
-Arterial emboli cannot end up in venous circulation
-Venous emboli cannot end up in arterial circulation, unless there is a patent foramen
-These are paradoxical emboli, which travel through a patent foemen ovale
-Whether an embolus causes infarction depends on site of embolization and collateral circulation


Systemic thromboemboli

-Thromboemboli in arterial circulation, from 5 major sources (first 3 most common): 1) left ventricular wall (mural) thrombi (most common), 2) left atrial wall (mural) thrombi, 3) valvular vegetations, 4) ulcerated atherosclerotic plaque, 5) aortic aneurysm
-Most common destination are lower extremities (75%) and brain (10%)
-Usually lead to infarction


Pulmonary embolism

-95% of the time from DVT
-Lodge in bifurcation of pulmonary trunk if big enough
-Most are small enough to remain asymptomatic and are lysed
-Whether or not infarction occurs is based on size of disrupted blood
-Lung has dual blood supplies (bronchial and pulmonary arteries), but bronchial arteries supply most of the lung oxygen
-Thus pulmonary emboli generally cause hemorrhage but not infarction
-But when a patient has left-sided CHF these emboli may cause infarct b/c the sluggish flow to bronchial arteries may not be enough to sustain tissue (congestion of lung)


Fat embolism

-Usually from bone fractures where fatty marrow is released into circulation
-May also be from subcutaneous fat due to trauma
-Often see diffuse petechial rash, respiratory distress, anemia, thrombocytopenia, neuro symptoms (these begin 1-3 delayed)
-Can also have whole chunks of bone marrow being mobilized


Atheroma embolism

-Necrotic lipid debris form inside a plaque due to rupture
-Can be accidentally released due to medical procedures
-Usually embolize to small arteries (usually in kidney, spleen, brain, bowel) and produce infarcts
-Identifiable by cholesterol clefts


Amniotic fluid embolism

-Amniotic membrane rupture, can cause DIC
-Cells of fetal origin can be found in embolism, including epithelial cells, hair, mucous droplets, and meconium (feces)


Gas embolism

-Can be due to medical care, penetrating injury, negative pressure in veins of head/neck/chest during inspiration
-At sufficient volume, molecules coalesce to behave as a solid
-Caisson syndrome (decompression sickness): resurfacing too quickly brings dissolved N gas from tissues into circulation where it can form bubbles and cause EC damage, platelet activation, cerebral and cardiac ischemia, pulmonary hemorrhage



-Can be localized (arterial/venous obstruction) or generalized (HF, shock)
-Local ischemia usually from arterial obstruction, based on: collateral circulation, integrity of collateral arteries, rate of obstruction development, tissue susceptibility, metabolic rate of tissue
-2 major organs w/ dual blood supply are lungs and liver


Chronic ischemia

-Chronic ischemia (usually from encroaching atherosclerosis, often in coronary artery disease) will cause affected region to decrease O2 tension by forming new collateral vessels
-Chronic myocardial ischemia: increased O2 demands results in transient ischemia (angina)
-Ischemia during sleep (or low cardiac activities) is sign of impending MI
-Chronic muscle ischemia (atherosclerosis) leads to calf pain
-Chronic ischemia leads to parenchymal atrophy (brain, kidney, heart)
-Only heart capable of angiogenesis in response


Ischemia from venous obstruction

-If there is collateral circulation (generally more than arterial) it must be blocked, insufficient to prevent ischemia, or peripheral leading to spill-over to necrotic area
-Will cause infarct (red) due to capillary rupture, ischemia
-Seen in renal vein and superior sagittal sinus veins



-Necrosis due to ischemia, vast majority due to arterial thrombosis or embolism
-Venous infarcts in renal and superior sagittal sinus veins
-Infarcts can be red (hemorrhagic, venous) or white (non-hemorrhagic, arterial) and wedged or triangle (based on vasculature)
-White (anemic) infarcts usually due to arterial obstruction in the heart, kidney, brain, spleen (poor collateral circulation)
-Wedge infarct occur in organs w/ hilum (lung, kidney, spleen)
-Shape of infarct does not indicate presence or absence of collateral circulation


Shock and hypovolemic shock

-Systemic reduction in tissue perfusion. Impacts: delivery of O2 and nutrients, removal of waste, thermoregulation
-3 kinds: hypovolemic, cardiogenic, generalized vasodilation
-Hypovolemic: large loss in blood volume (hemorrhage, fluid loss like vomiting or diarrhea, plasma loss from burns)


Cardiogenic shock

-Failure of heart to pump, usually due to MI but can also be from: arrhythmia, IV septal rupture, ventricular free wall rupture
-Ventricular free wall rupture causes blood to flow in pericardial space (cardiac tamponade) and prevents ventricles from contracting properly
-May also occur from massive pulmonary embolism (right can't pump hard enough)


Generalized vasodilation (w/ anaphylactic and neurogenic shock)

-3 types: anaphylactic, neurogenic, septic shock
-Anaphylactic: allergy hypersensitivity rxn (histamine, bradykinin, LT released by mast and basophil cells) that causes vascular permeability and exudate
-Neurogenic shock: from CNS injury or anesthesia, impairs neural control of vasomotor tone leading to increased vasodilation
-Does not lead to loss of fluid outside vessels, just redirected to periphery (reduced effective circulating doses)


Septic shock

-Infectious agents in blood cause host reaction
-Often due to endotoxin from GN (LPS) on cell wall binding to macrophages/PMNs and causing release of TNF and IL1
-Result is systemic vasodilation, decreased myocardial contraction, and EC damage that can lead to DIC


Stages of shock

-Compensation (nonprogressive): sympathetic reflex causes tachycardia and peripheral vasoconstriction (for vital organs). Have rapid, shallow berating, cold, clammy and cyanotic/pale skin, low BP
-Impaired tissue perfusion (progressive): prolonged vasoconstriction impairs tissue perfusion, resulting in hypoxia
-LA acidosis causes vasodilation, peripheral blood pooling, decreased cardiac output. Necrosis begins (first in renal tubules), then lung hypoxia w/ edema, hemorrhage hyaline fibrin membrane (shock lung), then intestine and liver fatty change, DIC may initiate
-Decompression (irreversible): complete loss of vasoconstriction, kidney failure due to acute tubular necrosis
-BP and cardiac output drop to critical, cerebral hypoxia causes brain dysfunction
-Bowel ischemia may result in bacterial seeding of bloodstream w/ superimposed endotoxic shock


Acute tubular necrosis

-Patchy or variable necrosis
-Some tubules are dead, some aren't (can still see some nuclei but in others you can't)
-Not due to infarct (unless it was transient),
-Shock is most common cause of acute tubular necrosis (glomeruli receive enough O2 and don't usually die)