Vascular Disturbances III Infarction

1
Vascular Disturbances III Infarction Shock
2
Infarction
3
Infarction

• 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

4
Appearance 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

5
Appearance of Infarct
NORMAL TISSUE
ARTERY
SURFACE FIBRINOUS EXUDATE
INFARCTED TISSUE
OCCLUSION
ILL-DEFINED INFARCT BORDERS
6
Types 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

7
Types of Infarct
Red pulmonary infarcts - dual pulmonary /
bronchial arterial supply
8
Types of Infarct
White splenic infarct
9
Event Sequence

1. Coagulative necrosis
2. Infiltration by neutrophils
3. Infiltration by macrophages
4. Phagocytosis of debris
5. Granulation tissue formation
6. Scar formation

10
Event Sequence
Day 1 3 7 14 90
11
Time 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
12
Infarct, day 0
Fibre eosinophilia contraction band necrosis
13
Infarct, day 1
Haemorrhage, necrosis and early neutrophil
infiltrate
14
Infarct, day 3
Myocyte necrosis, pyknosis and marked neutrophil
infiltrate
15
Infarct, day 7
Yellow necrotic infarct with hyperaemic border
16
Infarct, day 10
Granulation tissue after macrophage phagocytosis
of infarcted cells
17
Infarct, day 90
Subendocardial acellular fibrous scar
18
Infarct 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

19
Reperfusion 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

20
Reperfusion 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

21
Reperfusion 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

22
Shock
23
Shock (cardiovascular collapse)

• Final Common Pathway for a umber of potentially
  lethal clinical events
• Severe Haemorrhage
• Burns
• Trauma
• Large MI
• (massive) Pulmonary Embolism
• Microbial Sepsis

24
Shock (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

25
Types 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

27
Types 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

28
Types 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

29
Types 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

30
Septic 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)
32
Event 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

33
Event 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)

34
Event 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

35
Multiorgan 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

36
Stages 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

37
Consequences of Shock
Pink hyaline membranes lining alveolar spaces in
ARDS
38
Consequences of Shock
ATN swollen, sloughed and flattened
regenerating tubular epithelium, normal glomerulus
Normal glomerulus and tubules
39
Consequences 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

40
Summary

• Infarction
• Definition
• Infarct Types
• Timing of Infarcts
• Reperfusion injury
• Shock
• Types of shock and aetiology
• Stages of shock
• Consequences