14. Ischaemia, infarction and shock Flashcards
Is repercussion of non-infarcted but ischaemic tissues always good?
Generation of reactive oxygen species by inflammatory cells causes further cell damage (reperfusion injury)
What causes the majority of infarctions?
- thrombosis and embolism
- most common within arteries
Thrombosis and embolism causes the majority of infarctions but what else can cause it?
- vasospasm
- atheroma expansion
- extrinsic compression eg. tumour
- twisting of vessel roots eg. volvulus
- rupture of vascular supply eg. AAA
How can infarction by morphologically classified?
By colour
- red infarction
- white infarction
What is red infarction?
Haemorrhagic
Dual blood supply/venous infarction
What is white infarction?
Anaemic
Single blood supply hence totally cut-off
What shape do infarctions tend to be?
Wedge-shaped
Obstruction usually occurs at an upstream point, the entire downstream area will therefore be infarcted
What are the histological characteristics of infarction?
- coagulative necrosis (usually)
- colliquative necrosis (in the brain)
If a person dies suddenly (eg. massive heart attack), what do you see in the tissues?
Nothing!
No time to develop haemorrhagic/inflammatory response
What do you see histologically on a myocardial infarct?
Neutrophils entering the early lesion which progresses to fibrosis over time
What are the 4 factors which influence the degree of ischaemic damage?
- nature of the blood supply
- rate of occlusion
- tissue vulnerability to hypoxia
- blood oxygen content
How does nature of blood supply affect degree of ischaemic damage?
An alternative blood supply means less damage and so severe ischaemia is needed for infarction
Give examples of organs which a dual blood supply and are therefore less vulnerable to infarction?
- lungs (pulmonary and bronchial arteries)
- liver (hepatic artery and portal vein)
- hand (radial and ulnar artery)
Give examples of organs which have a single blood supply and are therefore more vulnerable to infarction?
- kidneys
- spleen
- testis
etc
How does rate of occlusion affect degree of ischaemic damage?
slowly developing occlusions are less likely to infarct tissues
allows time for the development of alternative (collateral) perfusion pathways
How are coronary anastomoses beneficial?
There are small anastomoses that connect major branches and have minimal flow. If a coronary arterial branch is slowly occluded, flow can be directed through these channels. Infarction can be avoided even if the main arterial branch is totally occluded
How vulnerable is the brain to tissue hypoxia?
Very vulnerable
If a neurone is deprived of oxygen, irreversible cell damage occurs in 3-4 mins
Brain is 1-2% of body weight but requires 15% of cardiac output and 20% of body oxygen consumption
How vulnerable is the heart to tissue hypoxia?
Slightly more resistant than the brain
Cardiac myocyte death takes 20-30 mins
What percentage of body oxygen does the brain consume?
20%
Which type of cell takes 20-30 minutes to die following oxygen deprivation?
Cardiac myocytes in the heart
How does blood oxygen content affect degree of ischaemic damage?
Reduced oxygen content (in anaemia etc) increased the chance of infarction
How does congestive cardiac failure increase chance of infarction?
In congestive cardiac failure there is poor cardiac output and impaired pulmonary ventilation
May develop an infarct with a normally inconsequential narrowing of the vessels
What is a watershed area?
Regions of the body that receive dual blood supply from the most distal branches of two large arteries, such as the splenic flexure of the large intestine and the brain
What are the ischaemic diseases of the heart?
- IHD (angina/MI)
What are the ischaemic diseases of the brain?
- cerebrovascular disease (TIA/CVA)
What are the ischaemic diseases of the intestines?
- ischaemic bowel
What are the ischaemic diseases of the extremities?
- peripheral vascular disease/gangrene
What is the leading cause of death in men and women in the West?
Ischaemic heart disease
What is characteristic of 90% of cases of ischaemic heart disease?
Impaired coronary arterial flow following complications of atherosclerotic disease
Are occluded coronary arteries clear to see?
Yes, there are visible both grossly with the naked eye and also histologically
What is the third leading cause of death in the West?
Cerebrovascular disease
What does cerebrovascular disease refer to?
Any abnormality of the brain caused by a pathological process involving the blood vessels
What are 2 types of cerebrovascular disease?
- ischaemic (thombosis and embolism)
- bleeding (haemorrhagic)
What are the causes of an ischaemic stroke?
- thrombosis secondary to atherosclerosis
- embolism eg. mural thrombus
What is a mural thrombus?
Thrombi that adhere to the wall of a blood vessel.
- occur in large vessels such as heart and aorta
- can restrict blood flow but usually do not block it entirely
What are the causes of a haemorrhagic stroke?
- intracerebral haemorrhage (hypertensive)
- ruptured aneurysm in the circle of Willis (subarachnoid)
What is a CVA?
Cerebrovascular accident (stoke)
Can be ischaemic or haemorrhagic
What would a patient with ischaemic bowel disease present with?
Abdominal pain
What is ischaemic bowel disease normally caused by?
Thrombosis or embolism in the superior or inferior mesenteric arteries
What are 3 different types of gangrene?
- dry gangrene
- wet gangrene
- gas gangrene
What is gangrene?
Infarction of entire portion of limb (or organ)
What characterises dry gangrene?
Ischaemic coagulative necrosis only
What characterises wet gangrene?
Superimposed infection
What characterises gas gangrene?
Superimposed infection with gas-producing organism eg. clostridium perfringens
What is shock?
A physiological state characterised by a significant reduction of systemic tissue perfusion (severe hypotension) resulting in decreased oxygen delivery to tissues
What is there an imbalance between during shock?
oxygen delivery and oxygen consumption
What does impaired tissue perfusion and prolonged oxygen deprivation during shock lead to?
Cellular hypoxia and derangement of critical biochemical processes at first cellular and eventually systemic levels
Shock causes hypoxia at first cellular then systemic levels. What effects does shock have on the cellular level?
- membrane ion pump dysfunction
- intracellular swelling
- leakage of intracellular contents into the extracellular space
- inadequate regulation of intracellular pH
- anaerobic respiration, creating lactic acid
Shock causes hypoxia at first cellular then systemic levels. What effects does shock have on the systemic level?
- alterations in the serum pH (acidaemia)
- endothelial dysfunction which leads to vascular leakage
- stimulation of inflammatory and anti-inflammatory cascades
- end-organ damage (ischaemia)
Is shock reversible or irreversible?
Shock is initially reversible but rapidly becomes irreversible
What are the sequential results of shock?
- cell death
- end-organ damage
- mutli-organ damage
- death
Give some different types of shock
- hypovolaemic
- cardiogenic
- distributive (has many subtypes)
Give some different subtypes of distributive shock
- anaphylactic shock
- septic shock
- toxic shock syndrome
- neurogenic shock
Anaphylactic shock is a type of which classification of shock?
Distributive shock
What characterises hypovolaemic shock?
Intra-vascular fluid loss (blood, plasma etc)
In hypovolaemic shock, there is intravascular fluid loss. What does this lead to?
Decreased venous return to heart (decreased pre-load)
Decreased stroke volume
Decreased cardiac output
In hypovolaemic shock, intravascular fluid loss leads to decreased cardiac output. How could this be compensated for?
cardiac output x total peripheral resistance = mean arterial pressure
Therefore, we can increase total peripheral resistance/ systemic vascular resistance (SVR)
= vasoconstriction = cool, clammy, “shut down”
What are the 2 classifications of causes of hypovolaemic shock?
- haemorrhage
- non-haemorragic fluid loss
Hypovolaemic shock can be caused by haemorrhage or non-haemorrhagic fluid loss. In what ways can haemorrhage be caused?
- trauma
- GI bleeding
- ruptured haematoma
- haemorrhagic pancreatitis
- fractures
- ruptured aneurysm
Hypovolaemic shock can be caused by haemorrhage or non-haemorrhagic fluid loss. In what ways can non-haemorrhagic fluid loss be caused?
- diarrhoea
- vomiting
- heat stroke
- burns
What is third spacing? (related to hypovolaemic shock)
Acute loss of fluid into internal body cavities
Third-space losses are common postoperatively and in intestinal obstruct, pancreatitis or cirrhosis
What characterises cardiogenic shock?
Cardiac pump failure
Cardiogenic shock is caused by cardiac pump failure. What does this lead to?
Decreased cardiac output
Cardiogenic shock is caused by cardiac pump failure which causes decreased cardiac output. How could you compensate for this?
Cardiac output x total peripheral resistance = mean arterial pressure
so increasing SVR would compensate for decreased CO
What are the 4 categories of cardiogenic shock?
- myopathic
- arrhythmia-related
- mechanical
- extra-cardaic
What is myopathic cardiogenic shock related to?
Heart muscle failure
What is arrhythmia-related cardiogenic shock related to?
Abnormal electrical activity
What is extra-cardiac cardiogenic shock related to?
Obstruction to blood outflow
What are the possible causes of myopathic cardiogenic shock?
- myocardial infarction (>40% left ventricular myocardium)
- right ventricular infarction, dilated cardiomyopathies
- “stunned myocardium” following prolonged ischaemia or cardiopulmonary bypass
What are the possible causes of arrhythmia-related cardiogenic shock?
- atrial and ventricular arrhythmias
- atrial fibrillation/flutters
- ventricular tachycardia, bradyarrhythmias and complete heart block (decrease CO)
How does atrial fibrillation cause arrhythmia-related cardiogenic shock?
Decrease in cardiac output due to impairment of co-ordinated atrial filling of the ventricles
How does ventricular fibrillation affect cardiac output? (and therefore causes arrhythmia-related cardiogenic shock)
Ventricular fibrillation completely abolishes CO (cardiac output)
What are the possible causes of mechanical cardiogenic shock?
- valvular defects (eg. prolapse)
- ventricular septal defects
- atrial myxomas
- ruptured ventricular free wall aneurysm
What is an atrial myxoma?
An atrial myxoma is a benign tumor of the heart, commonly found within the left and right atria on the interatrial septum.
What are the possible causes of 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
etc
What characterises distributive shock?
Decreased systemic vascular resistance due to severe vasodilation
Distributive shock is caused by severe vasodilation which decreases SVR (systemic vascular resistance). How could this be compensated for?
Cardiac output x total peripheral resistance = mean arterial pressure
Compensation = increase cardiac output = look flushed, bounding heart
Toxic shock syndrome is a subtype of which classification of shock?
Distributive shock
What causes septic shock? (a type of distributive shock)
Severe, overwhelming systemic infections
Gram+ve bacteria, gram-ve bacteria, or fungi
Who is more vulnerable to septic shock?
Immunocompromised, elderly, very young etc
Septic shock is caused by infection. How?
Infection leads to an increase in cytokines/mediators, this causes vasodilation
What is DIC (disseminated intravascular coagulation)?
Part of septic shock
Pro-coagulation
Widespread clotting/thrombi
Used all clotting factors and so also get haemorrhage
What type of reaction is anaphylactic shock?
Type 1 hypersensitivity reaction
Give examples of allergies which may cause anaphylactic shock?
Hospital e.g. drugs (penicillin etc)
Community e.g. peanuts, shellfish, or insect toxins
What do small doses of allergen cause in sensitised individuals?
IgE cross-linking
Mast cells contain IgE antibodies. What happens when this comes into contact with the antigen?
It causes mast cell degranulation
Which type of cell contains IgE antibodies?
Mast cells
During allergy/anaphylactic shock, mast cells release chemicals including histamine. What does this cause?
Vasodilation
Constriction of bronchioles/respiratory distress
Laryngeal oedema
What are the 2 ultimate problems in anaphylactic shock?
- low blood pressure
- difficulty breathing
What is characteristic of neurogenic shock?
Loss of sympathetic vascular tone
In neurogenic shock, there is loss of sympathetic vascular tone which causes widespread vasodilation. What is this caused by?
Spinal injury or anaesthetic accidents
Which bacteria causes toxic shock syndrome?
S. aureus
S. pyogenes
What do S. aureus and S. progenes produce that causes toxic shock syndrome?
exotoxins “superantigens”
What is unusual about superantigens?
They do not require processing by antigen-presenting cells
There is non-specific binding of class II MHC to T cell receptors
Therefore, up to 20% of T cells can be activated at one time
In toxic shock syndrome, superantigens are produced. What do they cause?
They activate lots of T cells at one time which causes widespread release of massive amounts of cytokines which decreases SVR (systemic vascular resistance)
What are ‘insensible losses’?
Fluid losses due to sweating etc.
What are the main reasons for shock in hypovolaemic, cardiogenic, and distributive shock?
hypovolaemic = intravascular fluid loss (decreased cardiac output)
cardiogenic = cardiac pump failure (decreased cardiac output)
distributive shock = severe vasodilation (decreased systemic vascular resistance)
What is the equation for mean arterial pressure?
cardiac output x total peripheral resistance = mean arterial pressure
What is equation for cardiac output?
heart rate x stroke volume = cardiac output
