2nd Year Pathology 2010 Vascular Disturbances III Infarction & Shock.

2nd Year Pathology 2010

Vascular Disturbances III Infarction & Shock


Infarction


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


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


Appearance of Infarct

ARTERY

OCCLUSION

NORMAL TISSUE

INFARCTED TISSUE

SURFACE FIBRINOUS EXUDATE

ILL-DEFINED INFARCT BORDERS


Types of Infarct Red (haemorrhagic) infarcts

1. Venous occlusion/congestion e.g. torsion2. Loose tissues where haemorrhage can occur and blood can

collect in infarcted zone e.g. lung 3. 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)

4. Tissues that were previously congested due to sluggish venous outflow

5. When flow is re-established e.g. fragmentation of an occlusive embolus, angioplasty

White infarcts1. arterial occlusion2. solid tissues, where haemorrhage limited e.g. spleen, heart,

kidney


Types of Infarct

Red pulmonary infarcts - dual pulmonary / bronchial arterial supply


Types of Infarct

White splenic infarct


Event Sequence

1. Coagulative necrosis

2. Infiltration by neutrophils

3. Infiltration by macrophages

4. Phagocytosis of debris

5. Granulation tissue formation

6. Scar formation


Event Sequence

Necrosis Neutrophils Macrophagephagocytosis

Granulationtissue

Fibrosis

Day 1 3 7 14 90


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

> 2 months Acellular collagenous scar Dense gray scar


Infarct, day 0

Fibre eosinophilia & contraction band necrosis


Infarct, day 1

Haemorrhage, necrosis and early neutrophil infiltrate


Infarct, day 3

Myocyte necrosis, pyknosis and marked neutrophil infiltrate


Infarct, day 7

Yellow necrotic infarct with hyperaemic border


Infarct, day 10

Granulation tissue after macrophage phagocytosis of infarcted cells


Infarct, day 90+

Subendocardial acellular fibrous scar


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


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


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


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


Shock


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


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


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


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


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


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


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


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


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


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)


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


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


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


Consequences of Shock

Pink hyaline membranes lining alveolar spaces in ARDS



Normal glomerulus and tubules ATN – swollen, sloughed and flattened regenerating tubular epithelium, normal glomerulus



Prognosis varies with cause and duration If circulatory disturbance corrected during nonprogressive

phase full recovery If progress to irreversible phase high mortality

Hypovolaemic shock > 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


Summary

Infarction Definition Infarct Types Timing of Infarcts Reperfusion injury

Shock Types of shock and aetiology Stages of shock Consequences

2nd Year Pathology 2010 Vascular Disturbances III Infarction & Shock.

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