Pathology - Haemodynamic Disorders Flashcards
define haemostasis
the process by which blood clots form at sites of blood vessel wall damage
two types of haemostasis?
primary and secondary
what is primary haemostasis?
the platelet plug forms by exposing collagen to VWF
what is secondary haemostasis?
fibrin meshwork formatin via exposure of tissue factor
the haemostasis sequence (4)
vasoconstriction
primary haemostasis
secondary haemostasis
clot stabilisation/resorption
why do vessels vasoconstrict?
reduce the blood flow to minimise blood loss
how is vasoconstriction regulated?
neurogenic factor - endothelin
where do you find Von Willebrand Factors?
in the blood plasma
how does primary haemostasis occur? (7)
- endothelial disruption
- collagen and VWF get exposed
- platelets in the blood bind to WBF
= via glycoprotein 1b - platelets change shape = spiky for SA
- platelets secrete granules
= ADP and Thrombin A2 - more platelets recruited
= aggregation for plug
how does secondary haemostasis occur?
- tissue factors are exposed
- coagulation cascade is activated
- extrinsic pathway
- factor 7 activated - thrombin formation
- thrombin cleaves soluble fibrinogen into fibrin meshwork
- thrombin activates more platelets
- RBC trap within the clot
what is Fibrinolysis?
the enzymatic breakdown of fibrin in blood clots
how is fibrinolysis activated?
tissue plasminogen activator - t-PA
secreted by endothelial cells
what is t-PA?
tissue plasminogen activator
what is the role of t-PA?
catalyse plasminogen into plasmin
plasmin breaks down fibrin
what do normal endothelial cells inhibit and promote?
inhibit coagulation cascade
inhibit platelet aggregation
promote fibrinolysis
5 Risk factors for endothelial damage.
hyperlipidaemia
diabetes
hypertension
toxins
smoking
what are the steps of atherosclerosis development? (8)
- endothelial damage
- increased permeability
- low density lipoprotein accumulates, platelets and monocyte adhesion
- macrophage migrate and activate
- smooth muscle cells recruitment
- lipid uptake and T cell activation
- chronic inflammation
- left with lesion, smooth muscle cells, lipid, macrophages with fibrous cap
what is critical stenosis?
if the atherosclerotic plaque grows and grows
and leads to ischemia
how can atherosclerosis lead to an aneurysm and rupture?
if there is muscle weakening
what happens if atherosclerotic plaque ruptures?
VWF factor, tissue factor can be exposed
- lead to thrombosis
- activate primary and secondary haemostasis
how can atherosclerosis lead to myocardial infarction?
rupture of atherosclerotic plaque
thrombosis
blocks blood supply to the heart
no oxygen
define thrombosis
the inappropriate activation of a normal haemostatic mechanism which results in the formation of a thrombus
define thrombus
a structured solid mass or plug of blood constituents formed within the heart or blood vessels
What are the 3 Factors of Thrombosis
Virchow’s Triad
- endothelial injury
- hypercoagulability
- abnormal blood flow
what constitutes virchows triad?
- endothelial injury
- hypercoagulability
- abnormal blood flow
Noxious Stimuli can be Pro-Thrombotic and lead to Endothelial Injury. Give 5 noxious stimuli.
- physical injury
- infection
- abnormal blood flow
- toxins - smoking
- inflammatory mediators
give 2 effects of a dysfunctional endothelial cells
- pro-coagulant effects
- anti-fibrinolysis
- decrease t-PA
give 3 proteinsthat a pro-coagulant decreases
decrease in:
thrombomodulin
protein C
tissue factor protein inhibitor
= all = anticoagulants
what are the 2 types of blood flow?
turbulence
stasis
3 Effects of Abnormal Blood Flow.
- activate endothelial cells
- become pro-thrombotic - disrupt normal flow
- platelets interact with endothelium - prevents dilution of clotting factors
Define Hypercoagulability
the abnormal tendency for blood to clot
What is the most common genetic cause for hypercoagulability?
mutation in factor V
= factor V Leiden
Name 9 secondary risk factors for hypercoagulability.
- immobilisation
- myocardial infarction
- atrial fibrillation
- prosthetic cardiac valves
- tissue injury
- cancer
- heparin-induced thrombocytopenia
- antiphospholipid antibody syndrome
- disseminated intravascular coagulation
What is Venous Thrombosis also known as?
Phlebothrombosis
what do venous emboli lead do?
pulmonary embolism
What is the Origin for Pulmonary Embolism?
DVT
Describe the steps of DVT to pulomary embolism
dvt fragments
embolus enters inferior vena cava
passes through right heart
stops in the pulmonary vessels
what is the dominant mechanism for Venous Thrombosis/Phlebothrombosis?
stasis
Where is Venous Thrombosis/Phlebothrombosis common?
deep veins of the leg DVT
what is the classical history of pulmonary embolism? (4)
- post hip replacement - immobile
- dyspnoea - shortness of breath
- hypoxia
- tachycardia
What is Arterial Thrombosis also known as?
Cardiac or Systemic Thrombosis
what are the 2 dominant mechanisms of arterial thrombosis?
turbulence and or endothelial injury of the heart
what 4 things can happen to a clot after thrombosis?
- propagation
- gets larger by accumulation of fibrin/platelets - dissolution via fibrinolysis
- organisation and recanalisation
- embolisation
what happens to a clot if it organises and recanalises?
it has an ingrowth of endothelial cells
forms new blood vessel channels
blood flows through
define embolisation
the formation of a detached intravascular solid, liquid or gaseous mass that is carried by the blood to a site distant from its point of origin
define embolism
the impaction of an embolus in a vessel whose calibre is too small to allow the embolus to pass leading to vascular occlusion
what are almost all emboli?
all emboli are thrombosis-emboli
what is an atherosclerotic emboli?
bits of atherosclerotic plaque are thrown into the blood vessel
- seen in aortic aneurysms
apart from thromboembolic, what are rare 6 types of emboli?
- atherosclerotic
- infective
- tumour
- gas
- amniotic
- fat
what are infective emboli?
lumps of infection break off
- often from heart valves
what are gas embolisms?
from rapid decompressions during diving
- develop nitrogen bubbles into blood
what is amniotic fluid embolism?
amniotic fluid goes into the mothers blood stream
what is fat embolism?
from trauma
fat can break off and embolism
what are the effects of large pulmonary vessels getting blocked?
saddle embolus
death
what % of plumonary flow leads to death if blocked?
60%
can a pulmonary embolism lead to instant death?
yes
what are the effects of small vessels getting blocked from pulmonary embolism?
dyspnoae and pleuritic chest pain - pain from inspiration
what % of small vessel obstructions are asymptomatic from pulmonary embolisms?
60-80%
80% of Systemic Thromboembolisms come from?
intra-cardiac mural thrombi
What can be the Effect of Arterial Thromboembolism?
ischemic injury
- limbs 75%
- brain 10%
- other viscera 15%
What is a Paradoxical Embolism?
embolus goes from the venous circulation straight to the systemic circulation to the rest of the body - brain, limbs or organs
How does a Paradoxical Embolism occur?
if a person has a heart defect or hole in the heart
What is the Route of a Paradoxical Embolism compared to a Regular Embolism in the Heart?
Regular:
- embolus arises from venous circulation
- through vena cava
- into right side of the heart
- into pulmonary circulation
Paradoxical:
- embolus goes from the venous circulation straight to the systemic circulation to the rest of the body - brain, limbs or organs
What is Hypoxia?
a state of reduced oxygen availability which causes cell injury by reducing aerobic oxidative respiration
Two Paths of Hypoxia to take
reversible
adaption
- if injury is not sustained
what happens if hypoxia is prolonged?
cell death - necrosis
What causes Hypoxia?
- inadequate blood oxygenation = generalised
- decreased blood oxygen-carrying capacity = generalised
How do you get Inadequate Blood Oxygenation?
- cardio respiratory failure
- lung failure
- low ambient oxygen e.g. altitude
how can a decrease in blood oxygen carrying capacity occur? (2)
- anaemia
- carbon monoxide poisoning
Define Ischaemia
localised tissue hypoxia resulting from a reduction in blood flow to an organ or tissues
how can ischaemia arise? (3)
- severe atherosclerosis
- thrombosis
- embolism
can ischaemia be reversible?
ONLY IF SHORT DURATION AND RAPID RESTORATION OF BLOOD FLOW
what type of cell death occurs in ischaemia?
necrosis
what is tissue necrosis when caused by ischaemia?
infarction
define infarction
tissue necrosis as a consequence of ischaemia
what is Ischaemia Reperfusion Injury?
if you reperfuse ischamic, dysfunctional tissues with blood
- generates ROS from inflam cells
= more cell damage
In Which Two Ways can Infarction be Classified according to Morphology?
colour
shape
What are the two types of infarction?
red - haemorrhagic
white - anaemia
How does Red Infarction Arise?
dual blood supply e.g. lungs
tissue is flooded with blood = red
venous infarction
blockage with tissue is flooded with blood
How does White Infarction Arise?
single blood supply cut off = white
Why are Infarctions Wedge-Shaped?
when obstruction occurs at an up-stream point
- the down stream branches will be infarcted
= wedge shaped
What is the Most Common Type of Necrosis in Infarction?
Coagulative
- good connective tissue
- framework is kept
e.g. kidney or heart
What Necrosis happens in the Brain?
Colliquative
If a person suddenly dies from heart attack, what would you see in the heart tissue?
nothing
no time to develop haemorrhage or inflammatory response to infarcted tissue
How does the heart appear less than 24 hrs after a MI?
appears normal
How does the heart appear 1-2 days after a MI?
pale red
oedema
neutrophil infiltration
How does the heart appear 3-4 days after a MI?
chronic inflammation overtakes
yellow
haemorrhagic edge
coagulative necrosis
macrophage infiltration
How does the heart appear 1-3 weeks after a MI?
pale and thin
granulation tissue formation
How does the heart appear 3-6 weeks after a MI?
dense fibrous scar
