CARDIOVASCULAR_PATH_MS2

• INFECTIOUS
• --SUBACUTE
• --ACUTE

• POST INFECTIOUS
• --RHEUMATIC FEVER

• NON-INFECTIOUS
• --NBTE
• --LIBMAN-SACKS

• SUBACUTE
• --AFFECTS ABN/Dz VALVES
• --LOW VIRULENCE ORGANISMS (viridians)
• --HOST REACTION PRESENT ON VALVES

• ACUTE
• --AFFECTS BOTH nL AND ABN/Dz VALVES
• --HIGH VIRULENCE (aureus)
• --HOST REACTION NOT PRESENT

• STRUCTURAL
• --VALVE Dz
• --CHD
• --PROSTHETIC VALVE

• BACTEREMIA
• --IV
• --DENTAL
• --INFECTION ELSEWHERE
• --CATHETER

IMMUNE DISFUNCTION

• CARDIAC
• --ABSCESS
• --VALVE FAILURE
• --MYOCARDIAL INJURY

SEPTIC EMBOLI

• IMMUNE COMPLEX
• --RENAL
• --SKIN
• --ARTHRITIS

ETIOLOGY

• HYPERCOAG STATES
• --MUCINOUS ADENOCARCINOMAS
• --SOME NON-MUC MALIGs (promyelocytic leukemia)
• --HYPERESTROGENIC STATES

• ENDOCARDIAL TRAUMA
• --INDWELLING CATHs

• VEGITATIONS
• --OCCUR ON nL VALVES

--SINGLE OR MULTI SMALL 1-5mm STERILE VEGs DISTRIBUTED ON LINE OF CLOSURE OF LEAFLETS

--MICROSCOPIC: BLAND THROMB w/o INFLAM INFILTRATE OR UNDERLYING VALVE DAMAGE. STERILE

ASSOC w SLE

• VAGITATIONS
• --SINGLE OR MULTI SMALL STERILE

• LOCATION
• --UNDERSURFACE OF MITRAL AND TRICUSPID VALVE LEAFLETS
• --CHORDAE TENDINAE
• --MURAL ENDOCARDIUM

• MICROSCOPIC
• --FINELY GRAN AND HEMATOXYLIN BODIES
• --UNDERLYING VALVE SHOWS INTENSE VALVULITIS w FIBRONOID NECROSIS
• --MILD TO SEVERE DEFORMITY POSS IN LATER STAGES

IMMUNE RESPONSE TO M PROT OF GAS CROSS REACTS TO SELF Ag IN HRT

DAMAGE BY BOTH HUMORAL AND CELL-MEDIATED

• CLINICAL FEATURES
• MAJOR
• --PANCARDITIS
• --MIGRATORY ARTH OF LRG JOINTS
• --SUBCUTE NODULES
• --ERYTHEMA MARGINATUM OF SKIN
• --SYDENHAM CHOREA

• JONES CRITERIA:
• EVIDENCE OF PREV GAS INF w EITHER:
• --2 MAJOR
• --1 MAJOR and 2 MINOR

• MINOR
• --FEVER
• --ARTH
• --ELEV ACUTE PHASE REACTANT

• EVIDENCE OF PREV GAS INF w EITHER:
• --2 MAJOR
• --1 MAJOR and 2 MINOR

• MAJOR
• --PANCARDITIS
• --MIGRATORY ARTH OF LRG JOINTS
• --SUBCUTE NODULES
• --ERYTHEMA MARGINATUM OF SKIN
• --SYDENHAM CHOREA

• MINOR
• --FEVER
• --ARTH
• --ELEV ACUTE PHASE REACTANT

FOCAL INFLAM LESIONS IN TISSUES

• DIFFUSE INFLAM IN ANY OF 3 LAYERS
• --ENDO
• --MYO
• --PERI

• ASCHOFF BODIES
• --FOCI OF LYMPHs, PLASMA CELLS, AND ANITSCHKOW CELLS (activated macros)

• ANITSCHKOW
• --CATERPILLAR CELLS
• --Dx FOR RHEUM FEVER
• --ABUNDANT CYTO
• --CENTRAL ROUND TO OVOID NUC
• --CHROM IN CENTRAL "RIBBON"

VALVES SHOW FIBRINOID NECROSIS IN CUSPS OR CHORDATE TENDINAE

OVERLYING SMALL VEGs ON LINES OF CLOSURE

DEFORMING FIBROTIC VALVULAR ABNs

• MITRAL STENOSIS +/- AORTIC STENOSIS
• --FISH MOUTH

CHORDAE TENDINAE THICKENED, SHORTENED, AND POSS FUSED

• MICRO
• --ORGANIZATION OF ACUTE INFLAM
• --DIFFUSE FIBROSIS AND NEOVASC OBLITERATING nL aVASC CUSP
• --ASCHOFF BODIES RARELY SEEN

• ATHERO
• --LRG ELASTIC AND MEDIUM MUSC ARTERIES

• ARTERIO
• --HT
• --SMALL MUSC ARTs AND ARTERIOLES

1) MAINTENANCE OF PERM BARRIER

2) MAKE ANTI-COAG, ANTI-THROMB, AND FIBRINOLYTIC FACTORS

3) MAKE PROTHROMB MOLs

4) MAKE ECM (collagen, proteoglycans)

5) MOD OF BLD FLOW AND VASC REACTIVITY

6) REGULATE INFLAM AND IMMUNITY

7) REGULATE CELL GROWTH

8) AFFECTS VASOREACTIVITY OF SMOOTH MUSC CELLS

ENDO DYSFUNCTION OR INJURY -> STIM SM AND ECM SYNTH

HEALING LEADS TO FORMATION OF NEOINTIMA BY ENDO CELLS MOVING TO INJURY

SM CELLS AND PRECURSERS MOVE TO INTIMA, PROLIF, AND SYNTH ECM. DO NOT CONTRACT

CELL PROLIF STOPS BUT INTIMAL THICK PERMANENT

PERSISTANT INJURY LEADS TO THICK

THICK IN nL VESSLES DURING AGING BUT w OUTWARD REMODELING

• 1) ARTERIOLOSCLEROSIS
• --CHRON HEMODYNAMIC STRESS
• --INC ECM SYNTH
• --INC SM, FOCAL NECROSIS severe

• SMALL MUSC ARTERIES AND ARTERIOLES
• --MAY CAUSE ISCH INJ

OCCURS IN HT AND DM

• 2) ATHEROSCLEROSIS
• --HIGH LIPID DIET
• --ECCENTRIC INTIMAL LESIONS PROTRUDE INTO LUMEN
• --THROMB FORMATION
• --WEAKENING UNDERLYING MEDIA AND poss ANEURISM

• 3) MONCKEBERG MEDIAL SCLEROSIS
• --CALCIFIED DEPOTS IN Pts > 50
• --NOT CLINICALLY SIG

• CONSTITUTIONAL
• --AGE > 40
• --MALES & POSTMENOPAUSAL WOMEN
• --GENETICS - FAM HIST

• MODIFIABLE
• --HIGH LIPID / CHOL IN BLD
• --HT
• --SMOKING
• --DM

• RESPONSE-TO-INJURY HYPOTHESIS
• --CHRON INFLAM & HEALING RESP OF ARTERIAL WALL TO ENDO INJ

• LOCATION AT SITES OF TURBULENT FLOW
• --OSTIA
• --BRANCH POINTS

• STEPS
• 1) ENDO DYSFUNC / INJ
• 2) ACCUM OF LDL IN VESSEL WALL
• 3) MONOCYTE ADHES AND MIG INTO INTIMA --> MACROs AND FOAM CELLS
• 4) PLATELET ADHES
• 5) PLATELETS/MACROs/ENDOs RELEASE FACTORS --> SM INTO INTIMA
• 6) SM CELL PROLIF AND ECM PROD
• 7) MORE LIPID ACCUM

• FATTY STREAKS
• --EARLIEST LESION

• PLAQUE
• 1) WHITE-YELLOW RAISED ECCENTRIC LESION within THROMB

2) PATCHY - NOT CIRCUMFERENTIAL

• 3) LRG & MED ARTERIES MOSTL
• --ABDOM AORTA >>> THORACIC
• --CORONARY > POPLITEAL > INT CAROTID > CIRC OF WILLIS

• 4) MICRO
• --FIBROUS CAP
• --CELLULAR AREA UNDER AND TO SIDE OF CAP w VASCULARIZATION
• --NECROTIC CORE
• --PLAQUES CHANGE/ENLRG OVER TIME

RUPTURE / ULCERATION / EROSION

• HEMORRHAGE INTO PLAQUE FROM NEOVASV AREAS
• --ATHER EMBOLISM
• --ANEURYSM FORMATION

OCCLUSION

• STENOSIS
• --CLINICAL AT > 70%
• --ANGINA
• --CHRON DIMINISHED PERFUSION
• --COLLATERAL CIRC MAY DEVELOP OVER TIME IN SOME

• ACUTE PLAQUE CHANGE
• --THROMB, HEMORR
• --ACUTE TISSUE INFARCT
• --STABILITY AND VULNERABILITY MORE IMP THAN % OCCLUSION
• --EXTRINSIC FACTORS. ADREN STIM INC BP, CIRCADIAN PERIODICITY OF MI, EMOTIONAL STRESS

• EMBOLISM
• DISTAL ISCH

UNPREDICTABLE, ABRUPT

SUPERIMPOSED THROMB

PARTIALLY OR COMP OCCLUDE ARTERY

• STEPS
• --INTRAPLAQUE HEMOR / RUPTURE
• --PLATELET ADHESION & AGG
• --THROMB FORMATION
• --OCCLUSION

• STABLE
• --SIGNIF OBSTRUCTION
• --DEMAND EXCEEDS SUPPLY
• --DEV OF COLLATERAL CIRC PROTECTIVE

• UNSTABLE
• --CRESCENDO
• --PARTIAL OCCL -> SEVERE TRANSIENT ISCH (15sec TO 15mins)
• --DOES NOT CAUSE NECROSIS
• --HARBINGER OF INFARCTION

90% DUE TO ACUTE PLAQUE CHANGE

• 10% OTHER
• --VASOSPASM
• --EMBOLI
• --VASCULITIS
• --SHOCK
• --etc

REVERSIBLE

--DEC ATP PRODUCTION

--INC LACTIC ACID

--LOSS OF CONTRACTILITY wi 60 sec

MAY LEAD TO HF BEFORE ACUTE MYOCARDOAL DEATH

STILL REVERSIBLE

GLYCOGEN DEPLETION

CELL SWELLING

IRREVERSIBLE

• DISRUPTION OF SARCOLEMMAL MEM INTEGRITY
• --INTRACELLULAR MACROMOLs LEAK INTO CIRC
• --MEASURES TO DETECT INJURY

>1 hr, MICROVASC INJURY

ANT LV WALL NEAR APEX

ANT INTERVENTRICULAR SEPTUM

CIRCUMFERENTIAL APEX

INF/POST LV WALL

POST INTERVENTRICULAR SEPTUM

INFERIOR/POSTERIOR RV FREE WALL

LV LATERAL WALL EXCEPT APEX

NONE

• GROSS
• NONE

• MICRO
• NONE TO FEW WAVY FIBERS

• GROSS
• OCCASIONAL MOTTLING

• MICRO
• EARLY COAG NECROSIS
• WAVY FIBERS
• CONTRACTION BANDS

• GROSS
• MOTTLING, PALE

• MICRO
• COAG NECROSIS
• PYKNOTIC NUC
• EARLY NEUT INFILTRATE

PICS 18-72 hrs

• 
• 

• GROSS
• PALLOR

• MICRO
• COMPLETE COAGULATION
• HEAVY NEUT INFILTRATE

• GROSS
• HYPEREMIC BORDER
• YELLOW-TAN SOFT CENTER

• MICRO
• DISENTIGRATION OF MYOCYTES
• EARLY PHAGOCYTOSIS

• 3-7 DAYS
• WEAKEST STRUCTURALLY
• PHAGO BUT NO COLLAGEN DEPOT
• MYOCARDIAL RUPTUTE
• DEATH FROM CARDIAC TAMPONADE

• PICS 4-10 DAYS
• 
• 

• GROSS
• YELLOW-TAN
• DEPRESSED MARGIN

• MICRO
• PHAGO
• EARLY GRANULATION

• GROSS
• GRAY-WHITE SCAR

• MICRO
• COLLAGEN DEPOSITION
• FIBROSIS

HEALED INFARCTS AFTER 8 WEEKS CANNOT BE DATED

• 3.5 WEEKS
• 

ALTERS MORPH OF IRREVERSIBLY INJURED CELLS

USUALLY HEMORRHAGIC

• CONTRACTION BANDS
• --FLOODING OF SARCOLEMMA w Ca INTO PLASMA

• PEAK
• 2-3 hrs

• ELEVATED
• 6-8 hrs

• RETURN TO nL
• 18-24 hrs

• PEAK
• 3-4 hrs

• ELEVATED
• 24 hrs

• RETURN TO nL
• 72 hrs

MOST SENSITIVE & SPECIFIC

• PEAK
• 4-8 hrs
• 3-4 hrs

• ELEVATED
• 48 hrs

• RETURN TO nL
• 7-10 days
• > 10 days

CONTRACTILE DYSFUNCTION --> LV FAILURE

ARRHYTHMIA

MYOCARDIAL RUPTURE

ANEURISM

MURAL THROMBUS --> EMBOLI

PERICARDITIS

INFARCT EXPANSION

PAPILLARY MUSC DYSFUNC/RUPTURE

PROG CHRON HRT Dz

STRUCT/FUNC OF CONNECTIVE TISSUE COMPROMISED

• POOR INTRINSIC QUALITY
• --MARFAN
• --EHLERS-DANLOS
• --VIT C DEF

• LOCAL INFLAM:
• --ATHEROSCLEROSIS
• --VASCULITIS

• LOSS/DYSFUNC SMC FROM ISCHEMIA
• --CYSTIC MEDIAL DEGENERATION (ssen in marfan, athero, ht, scurvy)

• ASSOC w ATHEROSCLEROSIS
• --INC METALLOPROTEINASE DEGRADES ECM
• --MEDIAL DEGENERATION

USUALLY BELOW RENAL ARTERIES & ABOVE BIFURCATION

>90% FROM HT MALES 40-60yrs

SMALL % YOUNGER (marfans)

• PATHOGEN
• --HT
• --NARROWING VASO VASORUM (cmd)
• --INTIMAL TEAR

aka TEMPORAL ARTERITIS

MEN > 50yrs

• GRANULOMATOUS Dz IN MED/LRG ARTERIES
• --PRIMARILY IN HEAD (temporal, opthal, vertebral arts)
• --NONCONTINUOUS

ELASTIC LAMINA FRAG

• CLINICAL PRESENTATION
• --HEADACHE or FACIAL PAIN
• --OCULAR Sx

Dx BY TEMPORAL ART BIOPSY

PULSELESS Dz

• YOUNG WOMEN < 50yrs
• --giant cell arteritis = men > 50yrs

• GRANULOMATOUS Dz OF LRG ARTERIES
• --AORTIC ARCH and poss branches
• --IRREG THICK --> NARROWING OR OBLITERATION

MICRO INDISTINGUISHABLE FROM GIANT CELL

• CLINICAL PRESENTATION:
• --CONSTITUTIONAL -- FATIGUE, WT LOSS, FEVER
• --ABSENT OR WEAK PULSES esp in UPPER EXTREMITIES
• --OCULAR
• --SYSTEMIC HT

TOBACCO USE

• YOUNG SMOKERS
• --MEN < 35-45yrs

• SHARPLEY SEGMENTAL VASCULITIS OF SMALL & MED ARTS
• --TIBIAL & RADIAL ARTs

CLAUDICATION OF FEET, LEGS, HANDS, ARMS, OR SUPERFICIAL SKIN