Pathophysiology of Thrombosis/Embolism and Ischaemia/Infarction Flashcards
What factors affect blood flow?
Pressure gradient Resistance Viscosity Velocity Compliance
What effects might abnormal factors have on blood flow?
Cause stasis or turbulent flow
What are some endogenous causes of thromboembolism?
Atheroma Hyperviscosity Spasm External compression Vasculitis Vascular steal
What is Virchow’s Triad?
Three factors contributing to thrombosis:
- changes in vessel wall
- changes in blood constituents
- changes in pattern of blood flow
What is a typical atheromatous pathogenesis of a thrombus?
Turbulent blood flow
Loss of intimal cells, denuded plaque
Collagen exposed, platelets adhere
Fibrin meshwork, RBCs trapped
Alternating bands - lines of Zahn
Further turbulence and platelet deposition
Propagation
> consequences
What are the consequences of a thromboembolism?
Depend on site, extent, collateral circulation
Common - DVT, ischaemic limb, MI
Resolution via organisation/recanalisation
Death
What are some types of embolus?
Thrombus Fat Gas Tumour Trophoblast (pregnancy) Septic material Amniotic fluid Bone marrow Foreign bodies
What are some risk factors for DVT and resultant PE?
Cardiac failure Severe trauma/burns Post-op/post-partum Nephrotic syndrome Disseminated malignancy Oral contraceptive Increased age Bed-rest/immobility Obesity PMH of DVT
Prophylaxis?
- TEDs
- S/C heparin
What is ischaemia?
Relative lack of blood supply to tissue/organ leading to inadequate O2 supply
What are the various types of hypoxia?
Hypoxic
- low inspired O2/PaO2
Anaemic
- abnormal blood
Stagnant
- normal inspired but abnormal delivery e.g. occlusion
Cytotoxic
- abnormal at tissue level
What factors affect O2 supply?
Inspired O2 Pulmonary function Blood constituents Blood flow Integrity of vasculature Tissue mechanisms
What can cause ischaemic heart disease?
Various supply issues:
- coronary artery atheroma
- cardiac failure
- pulmonary disorder
- anaemia
- previous MI
Demand issues
- exertion, stress
What are some clinical consequences of atheroma?
MI TIA Cerebral infarction Abdominal aortic aneurysm Peripheral vascular disease Cardiac failure Coronary artery disease (> MI)
What is infarction?
Ischaemic necrosis
What are some examples of causes of infarction?
Thrombosis/Embolism
Strangulation e.g. gut
Trauma - damaged vessel
What factors affect the scale of damage in ischaemia?
Time period
Tissue/organ
Pattern of blood supply
Previous disease
What is the short-term progression of events in maintained myocardial ischaemia?
Seconds = anaerobic metabolism, ATP depletion
< 2 minutes = loss of myocardial contractility
A few minutes = ultrastructural changes (cell swelling, relaxation, glycogen depletion)
20-30 minutes = irreversible damage
20-40 minutes = myocyte necrosis (troponin positive at this stage)
>1 hour = injury to microvasculature
How does the appearance of an infarct change with time?
<24 hours
- no visual changes
- 12 hours post - swollen mitochondria
24-48 hours
- pale infarct (myocardium, spleen, kidney, solid tissues)
- red infarct (lung, liver, loose tissues)
- acute inflammation at edge of infarct
72 hours +
- pale infarct goes to yellow/white and red
- red infarct little changes
- chronic inflammation, macrophages remove debris, granulation tissue, fibrosis
End result
- scar replaces area of damage
What are the long term progression of events in myocardial infarction?
4-12 hours
- early coagulation necrosis, oedema, haemorrhage
12-24 hours
- ongoing necrosis, myocyte changes, early neutrophilic infiltrate
1-3 days
- necrosis, loss of nuclei and striations, brisk neutrophilic infiltrate
3-7 days
- disintegration of dead myofibres, dying neutrophils, early phagocytosis
7-10 days
- well established granulation tissue with new blood vessels and collagen deposition
2-8 weeks
- increased collagen deposition
> 2 months
- dense collagenous scar
What is a transmural infarction?
Ischaemic necrosis affecting the full thickness of the myocardium
What is a subendochondral infarction?
Ischaemic necrosis mostly limited to a zone of myocardium under the endocardial lining of the heart.
What are some complications of an MI?
Can be immediate or later
Sudden death Arrhythmias Angina Cardiac faiure Cardiac reupture Reinfarction Pericarditis PE secondary to PE Papillary muscle dysfunction > mitral incompetence Ventricular aneurysm Dressler's syndrome
