Physiopathology Final Flashcards
When does blood allow for plug to occur
when healing needs to happen
Define hemostasis
- Blood vessels maintain fluid consistency of blood
- Maintenance of clot-free blood within the vascular system while allowing for the formation of a solid plug of blood under conditions of vessel wall injury (ex: thrombosis)
What is hemostasis a property of
BV and blood
Tunica intima is lined with what
Single layer of vascular endothelium that has to maintain its integrity–> non-damaged, non-inflammatory possess anti-platelet effects
Anti-platelet effects of intact endothelium (4)
- insulates platelets from subendothelial collagen
(physical barrier between collagen and platelets) - Prostacylcin (PGI2) synthesis- inhibits platelet agg
- ADPase synthesis- inhibits platelet agg
- Nitric oxide synthesis- vasodilation & inhibit platelet agg
ADPase synthesis in anti-platelet effects
Inhibits platelet agg; a lot of ADP? we are low energy situation–> can’t feed biological system. high ADP? high agg so produce ADPase to remove ADP–> inhibit agg
Nitric oxide synthesis in anti-platelet effects
Constitutively produced, sets normal vascular tone in body–> we always have some form of vasodil.
- Dilated so platelets go further away from eachother–> decreases agg
Anti-coagulant effects of intact endothelium
Heparin like molecule synthesis–> activates anti-thrombin III (degrades thrombin)
Effect of no thrombin on the coag system
Shuts off coag
What is the coag system
Release of fibrin to form lattice like system to plug up certain things
no coag system? No platelet agg
What turns on synthesis of antithrombin III
Herparin like factor
Fibrinolytic property of intact endothelium
tPA synthesis –> converts plasminogen to plasmin
What does plasmin do
Degrades fibrin (chews up clot)
Ischemic stroke
Patient produces fibrin clot in artery somewhere–> inject with tPA to clear clot
Hemorrhagic stroke?
Give tPA and you will kill them–> they can’t clot
Pro-thrombotic properties of damaged endothelium (4)
- Von Willebrand’s factor
- Tissue factor synthesis
- Platelet activating factor (PAF)
- t-PA inhibitor synthesis
von-Willebrand Factor
- Pro-thrombotic property of damaged endo
- Essential for platelet adhesion
- Expressed on surface and give platelets region to bind to
Von-Willebrand disease
-Mild, moderate or severe
-Severity determined by degree of loss of expression of VW factor
- Usually females of repro age
Sx: heavy menstrual flow
Mod/Severe? unable to maintain preg; hemorrhaging won’t occur of baby into wall–> spontaneous abortion
Tissue factor synthesis as a pro-thrombotic property of damaged endo
- Glycoprotein which activates coag system
- One of triggers for coag system
- Damage endo turns on tissue factor–> turns on coag system
Platelet activating factor as protrombotic property of damaged endo
damaged endo + PAF + platelets
t-PRA inhibitor ensures what
Clot will remain
*Plays important role in prothrombotic property of damaged endo
What are the “bricks” of a thrombus? Cement?
Bricks: platelets
Cement: fibrin
Platelet actions oppose the action of what
endothelium
Platelets secrete what (5)
Thromboxane (TXA2), ADP, Factors V and VIII, calcium
What do activated platelets bind to
Exposed collagen–> vWF
Activated platelet role in coagulation cascade
Initiates cascade (role of calcium and phospholipid complex)
“Temporary plug”
becomes definitive with formation of fibrin from thrombin = fused mass of platelets
Young clot appearance vs old clot appearance
Young: red, currant jelly
Old: can become permanent structures within BV
Coagulation System activated by who
- Activated by factor XII (hageman) or tissue factor
- End product is formation of fibrin monomers
- Fibrin is “cement” of thrombus
Thrombus
- An aggregate of platelets, fibrin and blood cells within the non-interrupted vascular system
- Adherent to vascular endothelium (vs a post-mortem blood clot) *Must be attached to BV wall!
- May arise in arterial or venous circulation
3 Predisposing factors to arterial thrombi
AKA Virchow’s Triad
- Damage to endothelium
- Alterations in normal blood flow
- Increased coagulability of blood
Damage to endothelium that will promote production of thrombus in region
- Ischemic damage to endocardium
- Valvular damage
- Free radical induced damage
Hemodynamic stress
Too much force on BV because of high BP
4 Alterations in normal blood flow: role of stasis and turbulence
- Physical damage to endothelium
- Disrupts laminar flow
- Prevent renal clearance of coag proteins
- Retards flow of anticoag’s to site of injury
Factors that increase coagulability of blood (5)
- Genetic defect in anticoag proteins or coag proteins
- Homocysteine: Increase either because of poor nutrition quality or a faulty gene
- Neoplasia–> release of procoagulants
- Polycythemia vera: too many RBC; high hematocrit
- Smoking, obesity “soft risk factor”
What is a soft risk factor
diet high in fatty acids–> blood becomes more viscous. This increases total peripheral resistance –> dictated by arterioles and capillaries
- Obesity = longer vasculature= increased TPR = increased BP= increased hemodynamic stress
50% of population will die from what
Arterial thrombi
*Most common cause of death in US
Most common sites of arterial thrombi
- Coronary
- Cerebral
- Femoral
Arterial thrombi results in what? Death due to?
Ischemic infarction
Death due to MI, cerebral infarct, renal infarct
Thrombosis in the venous system
- Phlebothrombosis
- Red thrombus –> occurs in venous system; leads to congestion that changes overall color of body part
- Most common in superficial leg veins (varicose veins)
- Deep leg vein thrombosis
Deep leg vein thrombosis
Most common clinical manifestation
aka “red thrombi”
arteries supply limb but veins can’t drain it
Lines of Zahn
Alternating layers of strata of a thrombus
- LIke tree rings
- Indicate a thrombus are not static structure; can grow and then stop and then grow some more
Mural thrombi (where is a good starting spot? type of growth?)
- Thrombus within wall of structure
- Left ventricle is a good starting spot
- Wart like vegetative growth
Mural thrombi mechanism
Recurrent rheumatic fever during childhood; Strep M protein
Mural Thrombi complications
~50% after second rheumatic fever
- antibody attacks own endo
- Growths can be hairlike; change characteristics of valve; decrease closure/less efficient
Verrucous (Libman Sacks) Endocarditis
Automimmune attack;
Lupus, vascular disease
Is a port-mortem clot a thrombus
No
Clinical manifestations of deep vein thrombosis (4)
- Unilat edema of foot and ankle –> can lead to bact skin infect
- Pain of foot and ankle (homan’s sign)
- Local ischemia - bacterial skin infections
- **Pulmonary embolization (largest risk)
Homan’s Sign
Apply broad contact to posterior knee–> they will be apprehensive
Where is the most common place for clot to form? Why?
Leg veins because lowest degree of pressure
What is one of most prevalent forms of death in hospital setting?
Deep vein thromboses
Economy Class syndrome
Increase likelihood of production of clot; present with posterior knee pain
5 Potential fates of thrombus
Dissolution (goes away); propagation (gets larger); organization (permanent inclusion of thrombus into BV wall; deposition of collagenous protein molecules); recanalization (attempt to increase BF through thrombus by burrowing thru it); embolization
Define embolism
Detached intravascular mass that is carried by the blood to a site distant form its point of origin
Subtypes of embolism
*Thromboembolism (MC); fat; air; amniotic
Thromboembolism
Most common subtype of embolism
Results in partial or complete occlusion of vessel lumina
May lodge in pulmonary or systemic circulation
What is the most common preventable death in hospitalized patients? How?
Pulmonary embolism
Use ambulation and anticoagulants
Where do pulmonary emboli arise from? where do they end up?
Arise from deep leg vein thrombi
Small vs large emboli (saddle embolus)
Saddle embolus
Saddles at bifurcation–> can lead to complete occlusion of both pulmonary aa
Systemic emboli: origin
ARTERIAL in origin (left ventricle, atherosclerotic plaques)
Systemic emboli: sites of lodgement (3)
Lower extrem (75%) (fem, tib, fib aa)
Brain (10%)
Visecera (10%)
Pathogenesis of systemic emboli
Typically starts with a cardiac event; the next question is where it will likely deposit
Infarction: definition; caused by
- An area of ischemic necrosis within a tissue or organ
- Most often caused by thrombotic or embolic occlusion
White Infarct
Cessation of blood; usually because of thromboembolus
Red infarct
Due to hemorrhage event; bleeding inartery supplying area
bleed into tissue–> tissue turns red
Determining factors of infarct type (3)
- Nature of vascular supply
- Rate of development of occlusion
- Vulnerability of tissue to hypoxia
Morphology of an infarct (4)
- wedge shaped
- Margins lined by rim of hyperemia/inflammation
- Surface covered by fibrinous exudate (deposited around margin of infarct)
- Coagulative necrosis
Define shock
Hypoperfusion of tissues; inadequate BS everywhere
5 Major subtypes of shock
Cardiogenic, hypovolemic, septic, anaphylactic, neurogenic
Neurogenic shock
Spinal cord and brain injury
ex: broken neck cuts cord vasodilates–> hard to maintain BP; paraplegic skin flushes red because skin requires neurogenic stim
Define cardiogenic shock
fail the heart as a pump; heart does not deliver adequate BS to entire body
Potential causes of cardiogenic shock (3)
Myocardial infarct; Cardiac tamponade; cor pulmonale
Myocardial infarct and cardiogenic shock
Heart muscle is dead–> can’t contract; decreases Cardiac output
Cardiac tamponade and cardiogenic shock
Develop a hole in heart so you bleed into pericard sac; heart is bathed in blood–> increases BP –> heart cannot beat effectively
What can cause cardiac tamponade
Thermogenics in diets
Hypovolemic shock definition
Not enough blood volume= decrease BP= slow blood= hypoperfusion
3 potential causes of hypovolemic shock
- Hemorrhage: some injury cause you to bleed out
- severe trauma: internal bleeding
- extensive burns: >40% of 3rd degree burns= actively weeping blood plasma= decrease in blood volume
Acute cor pulmonale and cardiogenic shock example
Presents in context of pulmonary embolism
Long flight–> complain of pulmonary issue–> embolism occludes pulm aa–> chemoreceptors in body notice blood acidity rise–> inc HR–> blood more acidic–> sudden cardiac collapse as result of exhaustion of occlusion of pulm trunk
Define septic shock
Inadequate pressure to move blood along because of increase vasc pressure and increase vasodil
Pathophysiology of septic shock
- Endotoxin release from gram neg bacteria (LPS)
- Endotoxin stimulate release of cytokines (IL-1, 6, 8, TNF)
- Cytokines trigger release of PAF, NO, Bradykinin, complement, prostaglandins, leukotrienes
3 Stages of shock
- Nonprogressive
- Progressive
- Irreversible
Nonprogressive stage of shock
Compensatory mechanisms to maintain BP= Symp NS, Renin Angio Aldost axis; autoregulation
*Attempt to maintain BP
Progressive stage of shock
Tissue hypoxia and metabolic acidosis
Tissues alive and functioning but heading down bad path
Irreversible stage of shock
Enzyme leakage; organ shut down
Cardiac and pancreatic enzymes in blood =
Organs are shutting down
Cytokines do what
Vasodilate and increase vasc perm
Endothelial activation: define
Endothel cells can change their behavior based on various pathophysiological stimuli
- anything that can damage or act upon endothelial cells can induce change
4 things endothelial cells can do once activated
- Express adhesion molecules: we want adherence to plug up hole
- Produce cytokines, chemokines: messenger molecules to call over WBC’s
- Produce growth factors
- Produce vasoactive molecules (vasodil/constrict)
Arteriosclerosis
- Hardening of arteries
- Caused by endothelial activation and subsequent pathological changes
3 distinct patterns of arteriosclerosis
- Atherosclerosis (elastic aa and muscular aa)**
- Monkeberg medial sclerosis (calcific deposits in musc arteries; hardening)
- Arteriolosclerosis (small arteries and arterioles; in context of diabetes)
Atherosclerosis contributes to what
- Half of all deaths
- Death due to IHD which leads to MI; accounts for 20-25% all deaths in US
Where do atherosclerotic lesions most occur occur
Elastic, large and medium muscular arteries
What is a fatty streak
Initial visible lesion that we can see
What is an atheroma
Lesion encroaches on lumen; accumulates fat in large arteries
Fibroatheroma
Lesion becomes necrotic
When does a lesion become complicated
The moment it produces clinically overt sx’s
Risk factors with atherosclerosis
Hypertension; hyperlipidemia (raw materials to build lesion itself); cig smoking; gender (males more and at earlier age; females more after meno); **diabetes; soft risks (sedentary lifestyle; stress; obesity)
New risks associated with atherosclerosis
Homocysteinemia; cytomegalovirus; C. pneumoniae; P. gigivalis
2 Lesions of atherosclerosis
- Fatty streaks: early intimal lipid accumulation and engulfment of macro’s
- Atheromatous placques: raised subintimal plaques of necrotic tissue, lipid, extracellular matrix and cells
Fibrous cap
Smooth muscle cells, macrophages, foam cells, lymphocytes, collagen, elastic, prots, neovasc
Necrotic center (4)
Cell debris, cholesterol crystals, foam cells, calcium
2 components of atherosclerotic lesion
Fibrous cap and necrotic center
4 resulting lesions of atherosclerosis
Ulceration, thrombosis, hemorrhage, calcification
4 Clinical manifestations of atherosclerosis
Acute occlusion
Chronic narrowing (tiny legs because lack BS)
Aneurysm formation
Embolism (plaque breaks off–> distal site)
Atherosclerosis of lumbar arteries
LBP; won’t respond to treatment
Aneurysm
Localized dilation of a blood vessel or chamber of the heart
5 types of aneurysm from most common to least
Aorta; iliac; splenic; renal; vertebral
2 categories of aneurysms
- True: where the aneurysm is bounded by arterial wall components; all 3 tunicas bow out–> inc. in diameter
- False: where a breach in the vascular wall leads to a vascular hematoma –> tear thru and cause vasc leakage into wall of vessel; can occur in any one tunica
True aneurysm (MC type? Where)
MC is atherosclerotic (direct consequence of lesion)
Syphilitic
COngenital
Left ventricular
False aneurysm
MC post myocardial infarctive
Junctional leak at vascular graft
Genetic
4 morphologies of aneuryms
Berry; fusiform; saccular; dissecting
Berry aneurysm
Most common in circle of willis Very small SPHERICAL dilation Rarely greater then 1-1.5cm Occur most frequently at base of brain Most commonly congenital; can become complicated *TRUE
Saccular aneurysm
Larger spherical dilation with same spherical shape as berry
Usually 5-10 cm in diameter
*TRUE
Fusiform aneurysm
Gradual and progressive dilation of blood vessel
May be eccentric (occur unilateral; bow out to side)
Spindle shape; common lower thor/upper lumb
*TRUE
Dissecting aneurysm
- Refers to escape of blood into tunica media
- Double barrel presentation of lumen
- Dilation of BV need not exist for dissecting aneurym to occur
- 2 types
- *FALSE
2 types of dissecting aneurysm
- in reference to aorta
1. Type A: include arch of aorta
2. Type B: Not include arch of aorta
DDX of aneurysm
Heart attack: elevates cardiac enzymes
Aneurysm does not
Pseudoaneurysm
aka traumatic aneurysm due to physical injury; tunica media relaxes –> transient dilation of BV
Produces focal dilation
Most common etiology of aneurysm
Atherosclerosis
What is claudication
Trouble walking
vascular and neurogenic
Atherosclerotic aneurysm presentation (Who? Diagnosed when? Symptoms 3, associated with what?)
- MC in abdominal aorta
- M>F (60-80 yoa)
- Diagnosed when >50% dilation of normal diameter of vessel has occurred
- Associated with hypertension (40%) + heart disease (30%)
- **Intermittent back and abdominal pain
- Claudication
- Lower limb ischemia
What is the greatest risk with atherosclerotic aneurysm
Chance of rupture
Imaging strategy for aneurysm
Depends on clinical presentation
Accidental discovery is extremely common when plain film MRI, CT taken for back pain evaluation
Clinical consequences of aneurysm >7cm
75% chance of rupture
2 non-inflammatory vascular diseases
Monkeberg medial sclerosis and raynaud phenomenon
Monkeberg Medial Sclerosis (define, most often where, et?)
- Degen calcification of tunica MEDIA of large and MEDIUM MUSCULAR arteries
- No luminal narrowing
- Most often aa of upper and lower extrem
- Et unknown
Monkeberg affects who the most
Older individuals
Monkeberg vs atherosclerosis
Monk does not lead to clinical presentation per se
Pipe Stem Calcification
Popliteal artery distribution –> we shouldn’t be seeing BV’s on xray
Doppler ultrasound to visualize BFlow thru vessel
Think MONKEBERG
Raynaud Phenomenon
- Cyanosis of digits of hand or feet
- Due to cold induced vasoconstriction
- Fingers change color in sequence
- Exaggeration of normal central and vasomotor responses to cold or emotion
Raynaud typically benign or malig
Benign; however longstanding cases amy show signs of atrophy of skin, subcut tissues and muscles
Rare ulceration or gangrene
Raynaud phenom vs raynaud disease
Disease is primary; phenom is secondary
Sequence of color change in raynaud phenomenon
White–> blue–> red (when area reperfuses with blood)
Inflammatory vasculitides
- Directs immune system toward component of BV wall
- Inflammation of walls of vessels (all sizes/types)
- Can classify based on pathogenesis/etiology
- Infection; immunologic
Clinical presentation of inflammatory vasculitides
- OFten a result of vessel lumen narrowing/oblit/dilat/thrombosis at that tissue level
- Vasculitides are steroid/immunosupp therapy responsive –> tx is similar because they are all infl. in nature
Takayasu arteritis
“Pulseless disease” : one arm normal, one are cold
- weakening of peripheral pulses
- Exam yields thickening of aorta, esp arch and its branches
- Near oblit of distal portions of aortic branches
Takayasu arteritis MC affects who
Females <40
When should you order a followup of takayasu
BP difference <10 points systolic between R and L arm
Polyarteritis Nodoasa
- Necrotizing vasculitis of small and med sized visceral arteries (arteries to organs)
- *NO lung involvement
- Presentation common in kidney, liver
Polyarteritis nodosa affects who
Males <40
3 Complications of polyarteritis nodosa
Aneurysm; thrombosis; infarct
TX of polyarteritis nodosa
Responds to corticosteroids (prednisone)
3 phases of Polyarteritis nodosa lesion
Acute, healing, scarred (may co-present)
affects different BV at different times
Polyarteritis nodosa presentation in kidney; liver
Kidney: hematuria
Liver: change in enzyme profile
Polyarteritis nodosa, when affecting small aa, can be associated with what
P- ANCA: antibodies that bind to neutrophil and casue them to be overactive in nature
Neutro’s release infl. mediators–> damage area–> inc. WBC’s
WBC’s supposed to be in tissue?
No–> infiltrate in polyart nodosa
Allergic granulomatosis and angitis aka
Churg- Strauss
Allergic granulomatosis
- Systemic vasculitis in young individuals with asthma*
- 2/3 patients have C-anca or P-anca
- small and med size aa and arterioles of lungs, spleen, kidney, heart, CNS and others
- Intense eosinophilic infilatrate
(Churg Straus)
Giant cell arteritis aka
Temporal arteritis
Giant cell arteritis
Patients >50 yoa
MC systemic form of vasculitis in adults
**Both acute and chronic form
Giant cell artertitis affects what
Large and small arteries, particulary in head
- *Patient presents with headache
- Can lead to blindness with ophthalamic artery involvement
giant cell arteritis immune reaction generated towards what? What is the nature of immune reaction? Injury?
Immune reaction is generated toward components of vascular wall- still putative
Granulomatous nature suggests T-cell mediated mechanism and antigen driven injury
Clinical features of giant cell arteritis
- Facial pain, intense upon palpation
- Ocular symptoms: mild to severe
- May lead to perm blindness
- Tx with anti-inflammatory
Kawasaki disease
- et is unknown
- disease of coronary arteries; children <4 yoa
- Associated with mucocutaneous lymph node syndrome (acute self-limiting fever, rash, erythema, desquamation, lymphadenopathy)
~20% devel cardiac sequellae…aneurysmal formation
Clinical consequences of Kawasaki disease (6 steps)
- Asymptomatic vasculitis
- Coronary artery ectasia: BV is widening but not yet aneurysmal
- Coronary artery aneurysm
- Thrombosis
- MI
- Sudden death
TX of kawasaki disease
Aspirin + intravenous gammaglobulin (helps modulate immune system)
Wegener’s Granulomatosis necrotizing vasculitis characterized by triad:
- Acute necrotizing granulomas of upper resp tract (arteries of resp) **COme in with pulm complaint
- Nectrotizing granulomatosis of small to med sized vessels (visceral aa)
- Renal disease in form of focal glomerulitis (renal disease)
Pathogenesis of Wegener’s Granulomatosis
- Some type of hypersensitivity reaction
- 90% present with ANCA. 75% with C-ANCA
- Rapidly fatal if not treated
- Tx with cyclophosphamide (chemo agent)
- Close to 100% cure when tx
Cyclophosphamide
- Tx for Wegener’s
- Highly effective chemo agent but carries high risk for secondary disease later in life
Thromboangitis obliterans aka
Buerger’s disease
Trhomboangitis obliterans
- Distinctive disease leading to vasc insuff in distal extrem’s
- Chx by segmental acute and chronic thrombosing of small and med aa
- Microabscesses/granulomatous inflammation
Clinical presentation of thromboangitis obliterans
Principally tib and radial aa
Preveiously occuring almost exclusively in heavy cig smoking men
Sx of claudication (neuro or vasc)
Cold intolerance/raynaud’s
Behcet
- Mainly involves mucous membranes
- Chx by oral apthous ulcers, genital ulceration, ocular inflammation and lesions in CNS, cardiovasc and GI
- Unknown cause, however immune basis
DDX: syphilis
Varicose veins
Enlarged tortuous BV’s
Et: increased intraluminal pressure
Women> men; familial predisp; obesity
Vessel walls may be thinned due to dilation or thickened due to hypertrophy
- Stasis dermatitis and secondary ulceration
Define varicosity
Dilation of a venous structure
What is the most significant varicosity
- Esophageal varicies
- Tend to harbor in pt’s with liver issue presenting with portal hypertension; inc intraluminal pressure of gut bulges into lumen of esoph–> becomes thinned and atrophy–> swallowing food is abrasive–> can cut open esoph and bleed into stomach
- Dec in BP = shock
Prognosis of esophageal varicies
50% esop varix die on first bleeding event
Within 1 year most will have a second bleeding event with same prognosis
Varicosities of rectum and anus
Hemorrhoidal veins increase pressure= hemorrhoids
Varicosities of scrotum
Pampiniform plex of veins–> toruous–> variocele–> mass within scrotal sac
Translumination test: light through structure? non-neoplastic
Thromophlebitis
Thrombus within a vein leading to inflammatory reaction
Phlebothrombosis
Thrombus in a vein independent of inflammation
Deep vein thrombosis associated with what? COD?
Prolonged bed rest, reduced CO, surgery
*Major threat to life; sudden death following post-op ambulation
Cause of death= pulm embolus resulting in cor pulmone (complete occlusion of pulm aa leaving lungs)
Is DVT symptomatic
- 50% of people don’t have symptoms
- General swelling in calf, ankle, foot or thigh (homan’s)
- Increased warmth of leg
Redness - Pain in leg
- Night leg cramps
- Bluish discoloartion of skin on leg or toes
Who has increased risk of DVT
Travelers; those in sitting posture; clotting illness; post-surg (esp if unable to walk)
Caval filter
Tx of DVT
Catches clot then administer streptokinase to break up the clot
Benign Hemangioma
- Common congenital vascular lesion
- OFten called a birth mark
- MC on skin, also on mucosal surfaces and visceral organs
- Present at birth and grow, but remain limited in size
Capillary hemangioma aka
- Strawberry hemangioma
Capillary hemangioma
- Vascular channels have the size and structure of normal capillaries
- Occur on skin, subcut tissue, muc membranes of mouth and lips
- Strawberry hemangiomas fade at 1-3 yoa
Cafe au lait spots
Multiple spots? seek genetic counseling; may have NF mutation–> skel defects, tumors, kyphoscoliosis
Cavernous hemangioma
- Lesions consist of LARGE vascular channels
- Skin (port wine stains), mucosa, viscera
- raised, spongy masses which do not regress spontaenously
- May undergo thrombosis, fibrosis, hemorrhage
INTENSE stain - Clinically signif in von Hippel Landau disease
- Increases density of capillaries
Balloon Angioplasty
- Luminal expansion of atherosclerotic arteries
- Atherosclerotic plaque becomes “unstable”
Complications of balloon angioplasty
- Plaque rupture, medial dissection, stretching of the media (exposure of collagen), prolif restensosis
1 symptom of heart attack
Angina
Stent
metal spring exerting pressure on BV wall to retain patency
