Pathology: abnormalities of blood supply Flashcards
(41 cards)
1
Q
Localized edema vs. systemic edema
A
- 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
2
Q
Transudate vs. exudate
A
- Transudate: noninflammatory edema due to increased hydrostatic pressure, decreased oncotic pressure, or lymphatic obstruction (no change in vascular permeability)
- Sp. Grav 1.015
3
Q
Hyperemia and congestion
A
- 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
4
Q
Pulmonary edema
A
- 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)
5
Q
Liver congestion
A
- 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
6
Q
Centrilobular fibrosis
A
- 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)
7
Q
Hemostasis
A
- 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)
8
Q
Factors of hemostasis
A
-Hemostasis is a balance btwn 3 pathways: coagulation, fibrinolytic (contains coagulation), and anticoagulation (regulates actions btwn coagulation and fibrinolytic pathways)
9
Q
Hemorrhage
A
- 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
10
Q
Hematoma
A
- Type of hemorrhage, localized blood within tissue
- Petechiae: smallest (pin point)
- Purpura: slightly larger
- Eccymoses: subcutaneous (bruises)
- Large accumulations (hemothorax)
11
Q
Thrombosis
A
- 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
12
Q
Causes of thrombosis
A
- 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
13
Q
Arterial thrombosis
A
- 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
14
Q
Atherogenesis (pt. 1)
A
- 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
15
Q
Atherogenesis (pt. 2)
A
- 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
16
Q
Cardiac (mural) thrombi
A
-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)
17
Q
Venous thrombosis
A
- 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)
18
Q
SVT
A
- 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
19
Q
DVT
A
- 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
20
Q
Outcome of thrombi
A
- 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
21
Q
Thrombolysis
A
- 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
22
Q
DIC: Disseminated intravascular coagulation
A
- 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
23
Q
Causes of DIC
A
- 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)
24
Q
Clinical presentation of DIC
A
- 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)
25
Emboli
- 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
26
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
27
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)
28
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
29
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
30
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)
31
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
32
Ischemia
- 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
33
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
34
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
35
Infarction
- 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
36
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)
37
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)
38
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)
39
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
40
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
41
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)
