Ischaemia and hypoxic injury Flashcards
define hypoxia
a state of reduced oxygen availability.
define ischemia
pathological reduction in blood flow to tissues.
what causes ischaemia
obstruction do to thrombosis.
Is ischaemia reversible
Yes if short duration
no is prolonged
what are 2 methods of artificial tissue perfusion
percutaneous coronary interventions for MI
thrombolysis for clots
why might reperfusion of ischema tissue might not be beneficial
1- tissue may be have undergone necrosis.
2-generation of reactive oxygen species by inflammatory cells can cause further injury
define reperfusion injury
generation of reactive oxygen species by inflammatory cells can cause further injury
define infrarction
Ischaemic necrosis caused by occlusion of the arterial supply or venous drainage
what is the most common cause of most infarctions
arterial thrombus or embolism
what are the causes of infarction
thrombus and emboli
vasospasm
atheroma expansion
Extrinsic compression (e.g. tumour)
Twisting of vessel roots (e.g. volvulus)
Rupture of vascular supply (e.g. AAA)
Vasculitis- inflammation of the blood vessels.
Hyper viscosity- thick blood
Steal.- blockage just after splitting of an atery into 2 so blood flows through the path of least resistance.
Venous occlusion- Also causes infarction but it is uncommon
define red infarct
(haemorrhagic)
Dual blood supply / venous infarction- e.g lungs has 2 blood supplies bronchial and pulmonary.
define white infarct
Single blood supply hence totally cut-off
what shape are most infarcts
wedge shaped
obstruction upstream so all of down stream is affected.
If a person dies suddenly (e.g. massive heart attack) what do you see in the tissues?
Nothing!
No time to develop haemorrhage / inflammatory response
Effects of vascular occlusion is variable and depends on four factors
these factors effect whether a tissue will become infected or not.
Nature of the blood supply
Rate of occlusion
Tissue vulnerability to hypoxia
Blood oxygen content
which organs have a dual blood supply
Lungs (pulmonary and bronchial arteries)
Liver (hepatic artery and portal vein)
Hand (radial and ulnar artery)
define watershed regions and give 2 examples
regions occur at the point of anastomosis between 2 vascular supplies.
splenic flexure and brain.
how does the rate of occlusion affect infarction
Slow developing occlusions are less likely to infarct tissues
Allows time for the development of alternative (collateral) perfusion pathways
Brain is 1 to 2% of total body weight but how much cardiac output and the oxygen of the body does it required
requires 15% of cardiac output and 20% of body oxygen consumption.
how long does it take the brain and heart to infarct without oxygen
brain-2-3 mins
heart- 20-30 mins
patients with what condition have reduced oxygen in the blood
Congestive cardiac failure
– Poor cardiac output and impaired pulmonary ventilation
– May develop an infarct with a normally inconsequential narrowing of the vessels!
define angina
chest pain due to ischemia / MI.
define stable angina
only comes about after physical exertion.
define unstable angina
develop chest pain more often at reduced levels of exercise or even at rest- indicates the plaque is enlarging and may even rupture.
what happens if you have ischamia of the brain
cerebrovascular disease.
what happens if you have ischamia of the the bowel
when you eat you need increase blood flow but if you cannot supply it due to volvulus then bowel dies.
what is the leading cause of death on both males and females
Ischaemic heart disease.
what is ischema of the heart known as
isachemic heart disease.
define cerebrovascular disease
Any abnormality of the brain caused by a pathological process involving the blood vessels
thrombus and embolism
bleeding (haemorrhagic)
causes of isachemic stroke
Thrombosis secondary to atherosclerosis
Embolism (e.g. mural thrombus)
causes of haemorrhagic stroke
Intracerebral haemorrhage (hypertensive)
Ruptured aneurysm in the circle of Willis (subarachnoid)
Berry anyersum- blockage in a blood vessel of the circle of willis.
If it burst then causes subarachnoid haemorrhage- pain in the back of the head.
causes of ischaemic bowel disease
Usually caused by thrombosis or embolism in the superior or inferior mesenteric arteries
what causes limb ischaema
Gangrene- Infarction of entire portion of limb (or organ)
Dry gangrene-Ischaemic coagulative necrosis only
Wet gangrene- Superimposed infection, Dry gangrene becomes wet gangrene is infected.
Gas gangrene- Superimposed infection with gas producing organism e.g. clostridium perfringens
define shock
A physiological state characterised by a significant reduction of systemic tissue perfusion (severe hypotension) resulting in decreased oxygen delivery to the tissues
cellular effects of shock
membrane ion pump dysfunction
intracellular swelling
leakage of intracellular contents into the extracellular space
Inadequate regulation of intracellular pH
anaerobic respiration-lactic acid.
Systemic effects of shock
Alterations in the serum pH (acidaemia)
Endothelial dysfunction - vascular damage.
Stimulation of inflammatory and anti-inflammatory cascades
End-organ damage (ischaemia)
Is shock reversible
Yes initially
No if prolonged.
what are the consequences of untreated shock
- Cell death
- End-organ damage
- Multi-organ failure
- Death
There are 3 types of shock
HYPOVOLAEMIC
CARDIOGENIC
DISTRIBUTIVE
what are the subcategories of distributive shock
ANAPHYLACTIC SEPTIC TOXIC SHOCK SYNDROME NEUROGENIC Others
what are the main events in hypovolaemic shock
Intra-vascular fluid loss (blood, plasma etc).
decreased venous return to heart AKA preload
decreased stroke volume so lower cardiac output.
what are the compensation mechanisms for hypovalaemic shock
- increase vasoconstriction so that heart rate increase which increases cardiac output.
- cold, clammy, tachycardia, shut down and oliguria(to prevent more fluid loss)
what cues hypovolaemic shock
Haemorrhage
Non-haemorrhgic fluid loss.- diarrhoea, vomitting, heat stroke and burns.
Third spacing- Acute loss of fluid into internal body cavities, third-space losses are common postoperatively
what are the main events in cardiogenic shock
Cardiac pump failure, cardiac output is reduced
How can you compensate for cardiogenic shock
increase systemic vascular resistance.
what are the 4 main causes of cardiogenic shock
Myopathic (heart muscle failure)
Arrythmia-related (abnormal electrical activity)
Mechanical
Extra-cardiac (obstruction to blood outflow)
what causes myopathic cardiogenic shock
MI infarction
right ventricular infarction- dilated cardiomyopathies.– “Stunned myocardium” following prolonged ischemia or cardiopulmonary bypass
what are the Arrhythmia-related cardiogenic shock
Atrial and ventricular arrhythmias
Atrial fibrillation / flutter causes decreased cardiac output, by impairment of co-ordinated atrial filling of the ventricles.
Ventricular tachycardia, bradyarrhythmias, and complete heart block decrease cardiac output while ventricular fibrillation abolishes CO.
what causes mechanical cardiogenic shock
Valvular defects (e.g. prolapse), ventricular septal defects
Atrial myxomas (benign tumour) , ruptured ventricular free wall aneurysm. Valvular
what causes Extra-cardiac cardiogenic shock
Anything that impairs cardiac filling or ejection of blood from heart
Massive pulmonary embolism, tension pneumothorax,
Severe constrictive pericarditis, pericardial tamponade (heart cannot dilate against pericardial sac as it is filled with fluid) etc
define distributive shock
have the same volume of blood but tissue perfusion decreases because it dosen’t get as far.
what is the main cause of distributive shock
decreased systemic vascular resistance
how do you compensate for distributive shock
increase cardiac output- flushed and bounding heart.
what are the 4 subtypes of distributive shock
SEPTIC SHOCK
ANAPHYLACTIC SHOCK
NEUROGENIC SHOCK
TOXIC SHOCK SYNDROME
what causes septic shock
systemic infections
what groups of people are more likely to get septic shock
Immunocompromised, elderly, very young
how does septic shock cause vasodilation (molecules)
cytokines
what causes anaphylactic shock
commonly drug allergy
Severe type I hypersensitivity reaction
how does anaphylactic shock cause vasodilation
– Small doses of allergen causes IgE cross-linking
– Massive mast cell degranulation
– Vasodilation
what are the consequences of vasodilation in anaphylactic shock
Contraction of bronchioles / respiratory distress
Laryngeal oedema
Decreased BP- struggling to breath.
Circulatory collapse resulting in shock / death
what causes neurogenic shock
Spinal injury / anesthetic accidents
how does neurogenic shock cause vasodilation
Loss of sympathetic vascular tone
Vasodilation
what causes toxic shock
S. aureus / S. pyogenes exotoxins aka “superantigens
how does toxic shock cause vasodilation
superantigens”- binds non-specifically to active lots of T ceels and lots of cytokines which decreases BP and decreases SVR.
causes vasodilation
is toxi shock T cell specific and require antigen presenting etc.
NO
define combined shock
Different types of shock can co-exist
patients with septic shock can have a combined shock with
– Primary distributive component • Inflammatory and anti-inflammatory cascades ↑ vascular permeability / vasodilation – Hypovolemic component • Decreased oral intake • Insensible losses • Vomiting, diahorrhea – Cardiogenic component • Sepsis-related myocardial dysfunction
