Title: Vascular Disturbances III Infarction
1Vascular Disturbances III Infarction Shock
2Infarction
3Infarction
- Tissue necrosis due to ischaemia
- vascular insufficiency of any cause
- usually arterial occlusion due to
thrombosis/embolism - Mainly due to oxygen deficiency, but toxin
accumulation reperfusion injury may contribute - Number of determining factors
- Size of vessel and size of vascular territory
- Partial / total vascular occlusion
- Duration of ischaemia
4Appearance of Infarct
- Wedge-shaped
- Occluded vessel at apex
- Periphery of organ forms base
- If extends to serosal surface, often overlying
fibrinous exudate - Lateral margins blurred due to collateral blood
supply
5Appearance of Infarct
NORMAL TISSUE
ARTERY
SURFACE FIBRINOUS EXUDATE
INFARCTED TISSUE
OCCLUSION
ILL-DEFINED INFARCT BORDERS
6Types of Infarct
- Red (haemorrhagic) infarcts
- Venous occlusion/congestion e.g. torsion
- Loose tissues where haemorrhage can occur and
blood can collect in infarcted zone e.g. lung - Tissues with dual blood supply e.g. lung small
intestine (permitting blood flow from
unobstructed vessel into infarcted zone note
flow is insufficient to rescue ischaemia) - Tissues that were previously congested due to
sluggish venous outflow - When flow is re-established e.g. fragmentation of
an occlusive embolus, angioplasty - White infarcts
- arterial occlusion
- solid tissues, where haemorrhage limited e.g.
spleen, heart, kidney
7Types of Infarct
Red pulmonary infarcts - dual pulmonary /
bronchial arterial supply
8Types of Infarct
White splenic infarct
9Event Sequence
- Coagulative necrosis
- Infiltration by neutrophils
- Infiltration by macrophages
- Phagocytosis of debris
- Granulation tissue formation
- Scar formation
10Event Sequence
Day 1 3 7 14 90
11Time Microscopic Features Gross Features
0 4 hr None None
4 12 hr Early coagulation necrosis (nucleus pyknosis, cytoplasm eosinophilia) None
12 24 hr Further necrosis, haemorrhage, early neutrophil infiltrate Dark mottling
1 3 days Marked neutrophil infiltrate and necrosis Mottled with yellow-tan necrotic centre
3 7 days Early phagocytosis of dead cells by macrophages (at border) Hyperaemic border, central yellow-tan softening
7 10 days Well-developed phagocytosis, early granulation tissue formation Maximal yellow-tan softening, depressed red-tan margins
10 14 days Well-developed granulation tissue, early collagen deposition Red-gray depressed infarct borders
2 8 wk Increased collagen deposition, decreased cellularity Grey-white scar progresses from border toward centre
gt 2 months Acellular collagenous scar Dense gray scar
12Infarct, day 0
Fibre eosinophilia contraction band necrosis
13Infarct, day 1
Haemorrhage, necrosis and early neutrophil
infiltrate
14Infarct, day 3
Myocyte necrosis, pyknosis and marked neutrophil
infiltrate
15Infarct, day 7
Yellow necrotic infarct with hyperaemic border
16Infarct, day 10
Granulation tissue after macrophage phagocytosis
of infarcted cells
17Infarct, day 90
Subendocardial acellular fibrous scar
18Infarct Development
- Dependent on a number of factors
- Nature of vascular supply
- Dual supply e.g. lungs, liver
- End arteries e.g. kidneys, spleen
- Rate of vascular occlusion
- Time for development of collateral circulation
- Vulnerability to hypoxia
- Neurons 2-3mins, Myocardium 20-30mins,
Fibroblasts hours. - Oxygen content of blood
- Anaemia, cyanosis, congestive heart failure
- Can result in infarction due to otherwise
inconsequential blockage - Size of vessel and size of vascular territory
- Partial / total vascular occlusion
- Duration of ischaemia
19Reperfusion Injury
- Possible effects of re-establishing blood flow
- prevention of all necrosis
- salvage of reversibly injured cells
- accentuation of damage to irreversibly injured
cells - new cellular damage
- Latter two constitute reperfusion injury
- Accentuated or new damage due to re-establishing
blood flow - Many effects of ischaemic injury only seen when
perfusion re-established
20Reperfusion Injury
- Can result in accelerated transition through
stages of infarct development - Timing of infarcts unreliable post reperfusion
- Inevitable if reperfusion occurs after optimum
salvage time e.g. usually 6 hours after
myocardial infarct - Characterised histologically by
- Marked haemorrhage
- Marked contraction band necrosis
21Reperfusion Injury
- Causes
- delivery of oxygen and calcium ions to damaged
tissue - interior of cells with damaged cell membranes
exposed to high Ca conc ? cell lysis - generation of oxygen-dependent free radicals by
damaged cells and phagocytes ? cell lysis - accentuation of O2-dependent damage
- Anti-oxidants have only small effect on tissue
loss - Acceleration of damage to irreversibly damaged
cells more than new cellular damage
22Shock
23Shock (cardiovascular collapse)
- Final Common Pathway for a umber of potentially
lethal clinical events - Severe Haemorrhage
- Burns
- Trauma
- Large MI
- (massive) Pulmonary Embolism
- Microbial Sepsis
24Shock (cardiovascular collapse)
- Circulatory failure resulting in inadequate
tissue perfusion (systemic hypoperfusion) - Results in
- hypotension
- impaired tissue perfusion
- cellular hypoxia
- reversible cellular injury
- irreversible cell injury and cell death
25Types of Shock
- Cardiogenic - due to myocardial pump failure
- Intrinsic damage (MI)
- Ventricular arrhythmias
- Extrinsic compression (Tamponade)
- Outflow obstruction (e.g. pulmonary embolism)
- Hypovolaemic - due to loss of blood or plasma
volume - Haemorrhage
- Fluid Loss from severe burns
- Trauma
26- Septic
- Systemic microbial infection
- Neurogenic
- Loss of vascular tone spinal cord injury
- Anaphylactic
- Generalised IgE hypersensitivity response-
systemic vasodilation
- - due to reduction in effective circulating blood
volume - peripheral pooling secondary to vasodilation and
- leakage of fluid due to increased vascular
permeability
27Types of Shock
- Cardiogenic
- myocardial pump failure
- e.g. myocardial infarction, ventricular rupture,
ventricular arrhythmia, cardiac tamponade,
pulmonary embolism - Hypovolaemic
- loss of blood or plasma volume
- e.g. haemorrhage, trauma, burns, vomiting,
diarrhoea
28Types of Shock
- Neurogenic shock
- peripheral pooling of blood due to loss of
vascular tone - e.g. anaesthetic accident / spinal cord injury
- Anaphylactic shock
- systemic IgE-mediated hypersensitivity reaction
to allergens e.g. bee stings, peanut - release of mast cell mediators
- systemic vasodilation and increased vascular
permeability
29Types of Shock
- Septic shock
- overwhelming microbial infection
- gram negative sepsis
- due to lipopolysaccharide (LPS / endotoxin) in
walls - gram-positive / fungal septicaemia
- due to molecules similar to LPS in walls
- Super-antigen release
30Septic Shock
- Usually due to lipopolysaccharide (LPS/endotoxin)
in walls of gram negative bacteria - LPS consists of fatty acid core and complex
carbohydrate coat - Similar molecules in walls of gram positive
bacteria or fungi - results in
- endothelial damage
- complement activation
- activation of macrophages with cytokine release
31(No Transcript)
32Event Sequence
- Low doses
- Local effects of LPS primary mediators (IL-1,
TNF) - Complement activation by LPS
- Monocyte/macrophage activation by LPS
- binding to surface receptors
- production of low doses of IL-1 and TNF
- Endothelial cell activation by IL-1 TNF
- production of IL-6 8 by endothelium
- increased adhesion molecule expression
- Recruitment of inflammatory cells and cytokine
cascade
33Event Sequence
- Intermediate doses
- Local effects of LPS secondary mediators (NO,
PAF) - Systemic effects of primary mediators (IL-1, TNF)
- Endothelial cell injury by LPS
- triggering of coagulation cascade
- increased vascular permeability
- production of secondary mediators by endothelium
- Local vasodilation due to secondary mediators
nitric oxide, platelet activating factor - Systemic effects of IL-1 and TNF
- Fever
- Acute-phase reactant production (CRP, fibrinogen)
34Event Sequence
- High doses
- Systemic effects of LPS, primary secondary
mediators - Widespread endothelial cell injury (LPS,
cytokines) - Acute respiratory distress syndrome
- Widespread activation of coagulation (LPS,
cytokines) - Disseminated intravascular coagulation
- Peripheral vasodilation, decreased cardiac
contractility (NO) - Hypotension
- Multiorgan failure due to hypoperfusion
35Multiorgan Failure
- Multiple organ damage due to ischaemia secondary
to hypoperfusion - brain ischaemic encephalopathy
- heart subendocardial infarcts
- kidney acute tubular necrosis
- GIT haemorrhagic enteropathy / ischaemia
- liver fatty change / centrilobular haemorrhagic
necrosis - ARDS in lungs commonly present concurrently
- Due to microvascular injury, not ischaemia
36Stages of Shock
- Nonprogressive phase
- Reflex compensatory mechanisms maintain perfusion
of vital organs - Tachycardia, peripheral vasoconstriction (pale
cold clammy skin), renal conservation of fluid
(anuria) - Progressive phase
- Tissue hypoperfusion metabolic imbalance
- Development of acidosis
- Due to anaerobic glycolysis and renal failure
- Causes arteriolar dilatation and peripheral
pooling of blood - Worsens hypotension and exacerbates tissue
ischaemia - Irreversible phase
- Irreversible cellular and tissue injury
- No response even if haemodynamic defects corrected
37Consequences of Shock
Pink hyaline membranes lining alveolar spaces in
ARDS
38Consequences of Shock
ATN swollen, sloughed and flattened
regenerating tubular epithelium, normal glomerulus
Normal glomerulus and tubules
39Consequences of Shock
- Prognosis varies with cause and duration
- If circulatory disturbance corrected during
nonprogressive phase ? full recovery - If progress to irreversible phase ? high
mortality - Hypovolaemic shock
- gt 80 90 survival in young healthy adults (10 -
20 mortality) - Cardiogenic shock due to MI / Septic shock
- up to 75 mortality even with appropriate
management
40Summary
- Infarction
- Definition
- Infarct Types
- Timing of Infarcts
- Reperfusion injury
- Shock
- Types of shock and aetiology
- Stages of shock
- Consequences