Download - Tissue Infarction And Repair - Year 2
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TISSUE INFARCTION & REPAIRDr R Pathmanathan
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INFARCTION( farcire‐“Stuffed full”)
I h i i (d th) d b l i Ischemic necrosis (death) caused by occlusion of either arterial supply or venous drainage in a particular tissuea particular tissue
An important cause of clinical disease and death Myocardial & Cerebral Particularly vulnerable
Pulmonary IntestinalE t iti ( ) Extremities (gangrene)
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INFARCTIONINFARCTION
M d i l l i Most cases are due to arterial occlusionusually thrombosis or embolism
l rarely spasm, hemorrhage, extrinsic compression, torsion edema “steal” syndromestorsion, edema, steal syndromes
Cases of venous thrombosis raremore likely in ovary and testis which have single more likely in ovary and testis, which have single venous outflowretina
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THROMBOSISTHROMBOSIS
Th b i Thrombosis: Thrombus formation in the circulation (thrombocytes fibrin cells) but not in vitro(thrombocytes, fibrin, cells), but not in vitro
ClotF d f fl i bl d Formed from non‐flowing blood
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INFARCTIONINFARCTION
A i d i h i fl Associated with an inflammatory response Gangrene is infarction of mixed tissue in bulk Infarction may also occur from partial vascular occlusion Interplay of diffuse tissue demands and length of ischemia
IRREVERSIBLE
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MECHANISM OF CELL DEATH IN INFARCTION
A i / h i Anoxia / hypoxia Trigger intracellular mechanisms of apoptosis
Reperfusion injury Reperfusion injury Damage is oxygen dependent Blood enters an area where cell membranes are Blood enters an area where cell membranes are damaged, calcium transport impaired
Trigger and activate O2 dependent free radical h b i h “ ” system that begins the “mop‐up” process
Recruitment of polymorphs and macrophages inflict further free radical mediated damageinflict further free radical mediated damage
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THROMBOSISTHROMBOSIS
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Virchow’s TriadVirchow s Triad
Endothelial injury Endothelial injury Stasis or turbulence of blood flow (aneurysms, varices, atrial fibrillation, hyperviscosity syndromes )Bl d h l bilit ( i d d ) Blood hypercoagulability (primary and secondary) Primary Abnormal clotting Factor V Variations in fibrinogenVariations in fibrinogen Protein C, Protein S deficiency Antithrombin III deficiency
Secondaryy Aging: decreased PGI2 synthesis in endothelial cells Heparine‐induced thrombocytopenia antiphospholipid (cardiolipin) antibody syndrome
ki d ( ) smoking, drugs, tumors (pancreas cancer)
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Virchow’s TriadVirchow s Triad
E d h li l i j Endothelial injury Stasis or turbulence of blood flow Blood hypercoagulability (primary and secondary)
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I‐ Endothelial InjuryI Endothelial Injury
Ath l i d H li id iAtherosclerosis and Hyperlipidemiaarterial intimal damage, irregularity
Trauma or inflammation of vesselsTrauma or inflammation of vesselsesp veins ‐ thrombophlebitis
Hypertension / Hemodynamic forcesHypertension / Hemodynamic forces arterial intimal damage
Cigarette smoke immune damage/ infections/ Cigarette smoke, immune damage/ infections/ toxins/ irradiation
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Platelet surface Membrane Receptors
Gp Ia‐ binds collagenGp Ib binds vWFGp Ib – binds vWFGpIIb/IIIa‐ binds fibrinogen & vWF
DEGRANULATIONAlpha granulesDense granulesDense granulesLysosomes
CALCIUMADP
ThromboxaneA2
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II‐Stasis or turbulence of II Stasis or turbulence of blood flow
A• Aneurysms• Persistent abnormal dilation of vessels
• Varices• Varices• Vessel tortuosity, usually venous
• Atrial fibrillationAtrial fibrillation• Inefficient emptying of blood from atria
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III‐Blood hypercoagulabilityIII Blood hypercoagulability(primary and secondary)
PrimaryPrimaryLeyden‐mutation (Factor V). A to G, protein resistant to cleavage by protein CProthrombin gene mutation ( G to A) increased PTlack of anticoagulants high level of homocysteinehigh level of homocysteine
SecondaryAging: decreased PGI2 synthesis in endothelial cellsHeparine‐induced thrombocytopeniaAntiphospholipid (cardiolipin) antibody syndromeS ki d t ( )Smoking, drugs, tumors (pancreas cancer)
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HISTOLOGY OF A THROMBUS
Arterial thrombus Fibrin meshwork is laid down
Platelets
R d Red Blood cells are trappedpp
FORMATION OF LINES OF ZAHN
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Th b i i iThrombosis in arteriesUsually occlusive; heart, aorta: usually mural h bthrombi
Thrombosis in veins thrombophlebitis, phlebothrombosis deep veins (90%), pelvic
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FATE OF THROMBUSFATE OF THROMBUS
L iLysisBlood flow is re‐established
E i ( th)Expansion (growth)OrganizationS i l d l f dScar tissue, mural nodule formed
RecanalizationSl bli h f bl d lSlow re‐establishment of blood supply
Embolizationl f f dLocalisation of fragments in distant sites
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EMBOLISMEMBOLISM
Detached intravascular solid, liquid or gaseous mass that is carried by the blood to a site distant from its point of origin
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Th b b li ( %) Thromboembolism (99%) Pulmonary thromboembolism (half of autopsies)
S d i ili f l i l i i Source: deep veins, iliofemoral veins, pelvic veins, right ventricle
Size: saddle → death; smaller (60‐80%) → infarct, Size: saddle death; smaller (60 80%) infarct, pleuradynia, hemoptysis, pleural effusion, dyspnoea, cough
l resolution, organisation
Paradoxical embolism (r →l)l b lArterial embolism
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Types of EmbolismTypes of Embolism
Ai b li Air embolism trauma (neck injury, hemodialysis), decompression sickness (caisson disease) >100ml decompression sickness (caisson disease) >100ml
Amniotic fluid embolismth b l ti DIC thromboplastin DIC
Fat embolism(b f ) trauma (bone fracture)
bone marrow embolism
T b li Tumor embolism
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DISSEMINATED INTRAVASCULAR DISSEMINATED INTRAVASCULAR COAGULATION (DIC) Acute subacute chronic thrombohemorrhagic disorder Acute, subacute, chronic thrombohemorrhagic disorder,
secondary to many diseases (obstetric complications infections, tumors, extensive tissue injury,
others)d h l l Sepsis, endothelial injury, extensive tissue injury
Release of tissue factor, thrombocyte aggregation Extensive microvascular thrombosis Occlusion of vessels (ischemic tissue injury)( j y) Consumption of clotting factors and thrombocytes Plasmin activation (fibrinolysis, cleavage of clotting factors)
BleedingP i Prognosis Different, depends mainly on the causative disease
Therapy: Nightmare Nightmare
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Types of InfarctTypes of Infarct
Cl ifi d b d Classified based on color ( red/ white )± infection ( septic / bland)
Actually stages of the same process, so the division may be meaninglessy g
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Red InfarctsRed Infarcts
H h i Hemorrhagic eg. venous occlusion
i t iovarian torsionloose parenchymal tissue
l b ilung, gut, braintissue with dual circulation
l lung , gutPassively congested organs
fRe‐perfusion injury
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White infarctsWhite infarcts
O l i f bl d l i lid i h Occlusion of blood supply in solid organs with end‐arterial circulation
H l kid Heart, spleen, kidney
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Morphology of infarctsMorphology of infarcts
W d h d Wedge‐shaped Occluded vessel at apex, periphery of organ forms basebase Fibrinous exudate on surface Hyperemic bordersHyperemic borders
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Factors influencing the Factors influencing the Development of an Infarct
N f V l S l Nature of Vascular Supply Rapidity of development of ischemia Tissue vulnerability to hypoxia Heart, CNS Bone, muscles – generally resistant
(Tissue demand for oxygen may be reduced by cooling
Oxygen content of blood
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Nature of Vascular SupplyNature of Vascular Supply
O d if d l bl d l / d Organs protected if dual blood supply/ good collaterals
L li h d f Lung, liver, hand, forearm
Susceptible organs are those with end arterial i l ticirculations Spleen, kidney
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Rapidity of development of Rapidity of development of ischemia
Sl l d l i l i Slowly developing occlusions Less likely to cause infarction
D l f ll l Development of collaterals
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Tissue vulnerability to hypoxiaTissue vulnerability to hypoxia
C ll ibili h i i Cell susceptibility to hypoxia varies Neurons ‐ 3 to 4 minutesM di l ll i Myocardial cells – 20 – 30 minutes
Fibroblasts – Many hours
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Infarction from Reduced Blood Flow or Oxygenation
“Water shed Areas” “Water‐shed Areas” Subendocardium Splenic flexure of colonSp e c e u e o co o Watershed areas in cerebral hemispheres
Portal vasculature / peculiarities of microvasculature Tissue perfused by blood already passaged through
one set of capillariesone set of capillaries Anterior pituitary Renal tubular epitheliumP i f i Portions of exocrine pancreas
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Watershed Areas of the BrainWatershed Areas of the Brain
Parts of the brain located at the ends of the Parts of the brain located at the ends of the distribution areas of the vascular systems are called the watershed areas.
“ A tertiary brain area located peripheral to primary distribution areas for anterior, posterior,
d iddl b l i i d i bl d i and middle cerebral arteries; it derives blood via the branches of all three cortical arteries." Because they are at the extreme ends of arterial Because they are at the extreme ends of arterial
distribution they are particularly vulnerable to ischemia and infarction in those who have circulation problems problems.
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Oxygen content of bloodOxygen content of blood
P i l l i l l i Partial occlusion vs. total occlusion
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Sequelae and Natural History‐1Sequelae and Natural History 1
I lid In solid organs Extravasated blood cells lysed
H id i l d h Hemosiderin laden macrophages
Dominant feature is ischemic coagulative necrosis Instantaneous death Instantaneous death No changes may be visible
12‐ 18 hours 12‐ 18 hours Only hemorrhage
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Sequelae and Natural History‐ 2Sequelae and Natural History 2
I fl t Inflammatory response Commences within hours ( reaction to dead cells) Well defined by 48 hrs Well defined by 48 hrs Reparative response Demolition phase (phagocytosis)p p g y
Fibrosis Scar tissue formation
Regeneration Stable and labile cells under some circumstances
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Special situationsSpecial situations
B i ff li f i i Brain suffers liquefactive necrosis If there is superadded infection, abscesses
f ( b l )may form ( septic embolism)