ischaemia, infarction and the results Flashcards
lecture 34
define ischaemia
an inadequate rate of blood flow to an organ. inadequate quantity not quality.
define infarction
necrosis due to ischaemia. a localised area = infarct
5 causes of ischaemia
1 - external occlusion (tumours, compression (bed sores))
2 - internal stenosis or occlusion, athero, thrombosis, embolism
3 - spasm of vessel ie cold in frost bite
4 - capillary blockage eg sickle cell, cerebral malaria
5 - shock
define shock
circulatory failure with low ABP, causing impaired perfusion of tissues.
4 causes of shock
1- cardiogenic - MI, arrythmia, outflow obstruction (pulmonary embolism), external compression.
2 - hypovolaemic - haemorrhage, severe burns
3 - septic - gram positive and negative bacteria
4 - anaphylactic - generalised type 1 hypersensitivity.
3 generic metabolic consequences of ischaemia
1 - hypoxia
2 - poor nutrient supply
3 - failure to remove waste products so may alter pH and electrolyt balance.
5 cells types in decreasing order of sensitivity to ischaemia
1 - neurons - very sensitive, irreversibly damaged by only 3 minutes of anoxia
2 - renal proximal tubular epithelium - sensitive, rapid impairment of ion reabsorption.
3 - myocardium - irreversible damage after 20 mins anoxia, but functional impairment (risk of dysrhythmia) in 1 minute.
4 - skeletal muscle - capable of anoxic work
5 - fibroblasts and macrophages - insensitive.
what affects an organ’s susceptability to ischaemia
largley the anatomy of the blood supply to it.
1 - collateral circulation may reduce susceptability. - venous circulation, some arterial systems (gut), can develop collateral if slow and progressive stenosis (coronary)
2 - organs with dual blood supply - 2nd may suffice. lungs = pulmonary and bronchial arteries and alveolar air. liver = hepatic portal vein and hepatic artery. brain = circle of willis
3 - single vessel = functional end arteries. very susceptible eg kidney, spleen.
8 factors affecting outcome from ischaemia
1 - anatomy of blood supply
2 - size of block (vessel size)
3 - degree of block (stenosis or occlusion)
4 - speed of onset (develop collateral)
5 -persistence of block - some thrombi are unstable
6 - vulnerability of the tissue
7 - demand of the tissue - inadequate on exertion (heart angina, leg in intermittent claudication)
8 - general inadequacy of the circulatory system ie coexisting anaemia, heart failure, shock etc
5 effects of ischaemia
1 - nothing
2 - functional defects (dysrhythmia, renal insufficiency)
3 - reversible cell damage (cell swelling, fatty change in myocardium (subendocardial zone) and hepatocytes (centrilobular region).
4 - infarction
5 - ischaemic reperfusion injury
microscopic appearances in infarction
1 - ischaemic coagulative necrosis
2 - acute inflammation at the viable margins
3 - some regeneration or organisation.
describe the changes in ischaemic coagulative necrosis
1 - visable 4-12 hours afterwards. earlier biochemical damage (eg enzyme leak)
2 - cytoplasm increase eosinophilia due to protein denaturation and loss of RNA.
3 - nuclei can undergo - karyolysis (pale), pyknosis (shrunken), karyorhexis (fragmentation)
4 - tissue architecture preserved for several days.
describe acute inflammation in infarction
developes at the viable margins within 24hrs.
describe tissue regen or organisation in infarction
liver may attempt regeneration but usually the infarct is organised. 3-5 days macrophages appear, granulation tissue develops. 6-8 weeks replaced by nonfunctional scar.
7 changes in the macroscopic appearance in infarction
1 - acute anoxia may - capillary dilation or haemorrhage hence poorly defined and red early on. 2 - pale infarcts 3 - red infarcts 4 - cone shaped/wedge shaped 5 - fibrinous exudate , red margins 6 - septic infarct and abscess 7 - liquefactive necrosis
describe pale infarcts
in soft tissue where infarct goes pale and rapidly demarcates in 24hrs. heart, kidney, spleen.
describe red infarcts
due to haemorrhage
arterial occlusion - in spongy tissue such as lung, tissue with collateral blood supply (gut), congested tissues.
venous occlusion
infarct shapes?
determines by blood supply. usually cone shaped with apex at point of occlusion and base at organ surface. = wedge shaped in 2 dimensions.
margins and exudate of infarcts
in early stages the margins of pale infarct can be red due to acute inflam and granulation tissue. may be a fibrinous exudate on the organ surface. eventually replaced by grey scar tissue.
secondary infection after necrosis
in some tissue ie lung. leads to a septic infarct and possibly and abscess.
brain infarct
undergoes liquefactive necrosis. necrotic cells are digested quickly, form a liquid containing cyst, surrounded by reactive glial cells.
define ischaemic reperfusion injury
when blood flow is restored to ischaemic cells that havent died and reversible injury becomes irreversible.
mechanisms of reperfusion injury
1 - generation fo fresh mdiators of cell injury - free radicals, calcium overload.
2 - initiation of acute inflammation by delivery of neutrophils and complement.
4 examples of infarction
1 - myocardial infarction
2 - cerebral infarction
3 - pulmonary infarction
4 - renal infarction
8 effects of myocardial infarction
1 - dysrhythmia 2 - sudden death 3 - cardiogenic shock 4 - rupture of the infarct 5 - mural thrombosis on the endocardium 6 - scarring 7 - adaptation to reduced CO - hypertrophy 8 - cardiac failure
common cause of cerebral infarction
common carotid thrombus or plaque that forms an embolus.
shock - common in the elderly
cause of pulmonary infarct
pelvic or leg vein thromboembolism
effect of pulmonary infarct
1 - silent
2 - impaired lung function
3 - pressure overload on right heart and right sided heart failure
4 - infection - septic infarct, abscess, pneumonia
5 - shock
cause of renal infarction
thromboemboli from the heart or elsewhere. kidneys recieve 25% of CO through one vessel so are at risk.
effects of renal infarct
small infarcts are often silent
- large - haematuria, renal failure.
