Circulatory Pathology Flashcards
lumen
The cavity or channel within a tube or tubular organ such as a blood vessel or the intestine
Blood vessel/arteriole: what is it and what cells/components line it
smallest artery before capillary
Endothelial cells line lumen (stretchy) making a basal lamina (basal membrane) to sit on. Smooth muscle cells found around basal lamina, with interstitial collagen fibres around them
elastic recoil
smooth muscle cells in blood vessels: work in stretching and the recoil
What does the blood vessel lumen contain
- RBC’s
- WBC’s
- platelets (white in colour and small)
- plasma (water and numerous proteins/other molecues)
Composition of plasma
non cellular (e.g. proteins like albium and immunoglobulins and other molecules)
What are platelets not normally exposed to
interstitial collagen fibres around vessel (normally stay in blood vessel and only touch endothelial cells)
components of blood other than plasma
3
RBS, WBC and platelets
What key element does plasma contain
clotting factors
what is serum
plasma without clotting factors
Explain clotting factors (origin and breifly summarise their action/pathway)
- Many are mainly produced in the liver (but also by endothelial cells)
- They are an amplification system, resulting in thrombin production
- Thrombin, in turn converts soluble fibrinogen into insoluble fibrin
- Fibrin forms a mesh of strands
What can the clotting cascade be known as
an amplification system
Since the clotting cascade is an amplification system what are many more molecules produced
fibrin compared to say, TF (tissue factor)
Clotting cascade pathway
see sheet
seriously, actually learn this one
clotting cascade function
detects initial damage, binds up bacteria & injured cells to keep them from causing more harm in areas
Initial drama to cause clotting cascade
Obvious one is trauma
Leads to:
1. exposure of interstitial collagens (collagens in CT between structures)
2. Eposure of a molecule called tissue factor (TF)
process leading to clotting cascade
trauma= interstitial collagens exposed and TF exposed
- trauma results in defects in vessels
- blood leaks out and serum comes into contact with interstitial collagen fibres
- plasma clotting factors can now be activated as they contact interstitial collagens
- TF released from smooth muscle cells
- TF can now bind a particular clotting factor and initiate the clotting cascade
how does a clotting factor become activated
When your body detects a bleed, the clotting factors are switched on in a particular order, one after the other. Each factor activates the next until they form a clot
clotting factors as serine proteases
Many clotting factors are serine proteases - that is they have a serine amino acid in them and they cleave other clotting factors to form the active molecule
what do clotting cascades lead to the production of and what does this do
- production of thrombin from prothrombin
- thrombin converts soluble fibrinogen to insoluble fibrin
- endpoint of clotting cascade production of insoluble fibrin strands that form meshwork
fibrinogen vs fibrin
see sheet
platelets - origin
- Produced in bone marrow
- From cell called a megakaryocyte
- Megakaryocyte = Large cell with many nuclei
megakaryocyte in bone marrow- formation of platelets
undergoes nuclear division but not cell division so get huge cell with many nuclei, platelets bud off as fragments from cytoplasmic extensions
how do platelets work
- trauma to vessel-> exposure of platelets to interstitial collagen
- platelets adhere together try to form bridge to close gap
coagulation - meaning and types
Solidification of blood
- Thrombus formation
- Clot formation
thrombus formation/facts
- occurs in flowing blood
- pure thrombus= pale cream coloured
- thrombus consists of platelets and a mesh like network of fibrin strands
-thrombosis (process of thrombus formation) occurs in flowing blood
why does a thrombus of platelets and fibrin occur in flowing blood
platelets have molecules on their surfaces which allow adherence to interstitial collagen, even when blood is flowing past them - the clotting cascade deposits Factor VIII which enhances this further
explain clot formation
- blood leaks out of a vessel and becomes stationary/stagnant
- within the stagnant blood- clotting cascade activated
- clot consists of a network of fibrin strands and red blood cells
colour of clot
red (due to prescence of RBC)
haemostasis
stopping bleeding
Give an example of haemostasis in normal skin with a wound
(stopping bleeding)
- vessel surrounded by collagen
- blood flows through vessel in skin
- trauma to skin disrupts one side of vessel
- blood, including RBCs leaks out
- clotting system activated by collagen and stagnant blood, forming clot
- may not work perfectly and wound may continue to bleed
- vessel vasoconstricts to decrease blood loss
- platelet and fibrin thrombus forms to bridge the gap between the ends of the vessel adjacent to flowing blood
- skin now stops bleeding - haemostasis has been achieved
3 things that can happen in wound due to trauma to stop bleeding
- Vasoconstriction - helps dec bleeding
- Clot formation occurs in space around vessel and may fill void of wounded tissue
- Thrombus forms in flowing blood and stops bleeding from gaps in vessels
granulation tissue
-new vessels that grow into area of wound
-the capillaries that grow in (granulation tissue) can oxygenate the area of the wound and keep it alive
-scarring etc. then happen
how is the thrombus removed
Plasminogen converts to plasmin, and plasmin cuts up fibrin into smaller fragments, as a way of removing fibrin (in both clots and thrombi). In a thrombus this is sometimes called thrombolysis
thrombolysis
lysis (splitting) and removal of the thrombus
how is excess thrombus or clot removed (in blood)
In blood there is a fibrinolytic system which removes fibrin and stops thrombi from propagating,
what do fibrinolytic system depend on
- Plasminogen being converted to plasmin
- Plasmin cuts up fibrin into fibrin degradation products
what cuts up fibrin in a thrombus
plasmin
What 2 thing must be in balance to stop bleeding but also ensure a capillary/vessel does not get blocked
fibrinolytic and clotting systems
What are thrombosis and clotting normal in
- wound healing
- stopping bleeding during menstruation
3 main causes/predisposing situations that may result in thrombosis
LEARN ME
1.Changes in the intimal surface of a vessel (e.g. trauma)
2.Changes in the pattern of blood flow
3.Changes in the blood constituents
known as Virchow’s triad
summarise thrombi in 1 sentence
platelets admixed with fibrin and form in flowing blood
summarise clot in 1 sentence
fibrin admixed with RBC and forms in stagnent blood
3 important factors in wound healing
thrombosis, clotting, vascoconstriction
main site of production of clotting factors
liver
physiological thrombosis
normal after cut or other injury
pathological thrombosis
occurs in absence of a cut or traumatic injury
Virchow’s triad
- changes in the intimal surface of a vessel
- changes in the pattern of blood flow
- changes in the blood constituents
example of virchow’s triad- coronary artery thrombosis
- coronary arteries supply heart muscle
- smoking increases ‘stickiness’ of platelets
- makes it more likely that a thrombosis occurs
- alteration in properties of blood= change in blood constituents which is part of virchow’s triad
what can predispose to atheroma in the coronary arteries
cigarette smoking (/high lipid in blood etc.)
atheroma
- disease of coronary arteries which results in the build up of lipid under the intimal surface
- lipid can result in abnormal blood flow (can get both slow and turbulent flow)
- Slowed blood flow predisposes to fibrin and platelet clumping
- Lipid (and collagen) can also rupture through the intimal surface
- platelets and fibrin now exposed to an abnormal substance (lipid and collagen) and turbulent flow and are deposited as a thrombus
- thrombus blocks the lumen of the coronary artery
- Clot can now form in the stagnant blood behind the thrombus
(change in pattern of flow = virchow’s triad)
what does atheroma result in
(big) blood clot behind (small) thrombus
briefly describe the more complex layers of atheroma/clot in blood vessels
1st - thrombus (platelets and fibrin)
2nd - RBC trapped in fibrin meshwork
3rd - complex structure protrudes even further into lumen causing more turbulence/slowing so get 3rd layer of thrombus
And so on…
what do multiple layers of thrombus and clot lead to
lines of Zahn
(pale layers of thrombus alternating with red layers of clot)
Do we need all 3 of Virchow’s triad to get a thrombus/clot formation
No just 1 badly
Where can thrombus/clot formation happen
arteries, veins, capillaries, pre-capillaries
What could all 3 situations occuring in Virchow’s triad lead to
coronary artery thrombosis
what happens when a thrombus blocks an artery
- Complete obstruction leads to no flow beyond blockage
- Partial obstruction leads to decreased flow beyond blockage
- The tissue supplied by this artery receives less blood flow
ischaemia
poor blood flow leading to decreased oxygenation of tissue - hypoxia
ischaemia
- An inadequate supply of blood to a part of the body caused by blockage of an artery
- If it is severe enough ischaemia leads to decreased oxygenation of tissues (=hypoxia).
- The tissue is said to be ‘ischaemic’- localised area of tissue dies
How does ischaemic heart tissue feel
painful
what could cause a localised area of tissue to die
severe or total blockage of blood flow meaning the lack of blood flow (ischaemia) leads to severe lack of oxygen (hypoxia) and causes a localised area of tissue to die
infarct
tissue death or necrosis due to inadequate blood supply to the affected area
necrosis
tissue death
infarct/infarction - name means what
name reserved for necrosis as a result of ischaemia (=ischhaemic necrosis)
infarcts occurring in certain tissue types
virchow’s triad causing thrombosis and clotting…
-Coronary artery thrombosis - infarct in heart
-Cerebral artery thrombosis - infarct in brain
-Mesenteric artery thrombosis - infarct in gut
what is an embolism
- A mass of material moving in the vascular system and able to become lodged in a vessel and block its lumen
- Most emboli are derived from thrombi or clots
- They break off and go elsewhere in the circulation
thromboembolism
when thrombi/clots embolise
common example of thromboembolism
pulmonary embolism
how does pulmonary embolism occur
- Sluggish flow in leg veins leads to thrombosis and clot formation
- Part of thrombus (and clot) breaks off and travels up vein
- Embolus passes into inferior vena cava, then right heart, then pulmonary trunk, and lodges in pulmonary artery branch
- Embolus blocks pulmonary artery and get pulmonary infarct
breifly outline other forms of embolism
(other than pulmonary embolism)
- marrow embolism (from leg fracture)
- Air embolism (air entering vein —> air embolism in heart)
Give a major example for each situation of Virchow’s triad
- changes in the intimal surface of a vessel - etheroma lipid coming ont surface
- changes in the pattern of blood flow - a bulge of atheroma changing the flow of blood
- changes in the blood constituents - smoking making it more likely that platelets aggregate
anoxia
a state of total oxygen deprivation within tissues or organs - extreme form of hypoxia
what kind of problems can ischaemia cause
- Reversiable problem
- Localised death of tissues (infarction) - permanent
sensitive organs to ischaemia
brain/kidneys???
LO but not mentioned in power points
define circulatory shock
profound circulatory failure causing poor perfusion of vital organs
(low blood pressure and its physiological consequences)
what does the sringy/elastic property of vessels allow
them to collapse when no blood is in them, or open up when blood is present
normal arterial blood pressure
120/80
What does normal blood pressure rely on
- enough blood in system (about 5L)
- smooth muscle in vessels having a certain ‘tone’ (if dec, vessel dialates cause pressure to fall)
- heart pumping blood
how does the body detect blood pressure and oxygen
- 2 cartoid bodies and 2 carotid sinuses on either side of neck
- 2 carotid bodies consist of groups of cells which sense the partial pressure of oxygen
- carotid sinuses respond to blood pressure- sense when it drops and carotid sinuses respond by nerve signals to the brain stem
-brain stem then tells the heart to pump harder and faster via nerve signals
=> pulse is faster
what is the physiological response to low blood pressure
generally
Faster pulse (heart rate)
What does the brainstem also do (other than inc pulse) to keep someone alive in response to low blood pressure
- sympathetic nervous system stimulation causes increased vascular tone in vessels in limbs and abdomen-> blood pushed up to chest and head
- results in circulation of remaining blood around heart, lungs and brain- keeps vital organs alive
- sympathetic nervous system stimulation also causes adrenal glands to secrete adrenaline-> heart pumps even harder and faster
when is circulatory shock present
- low blood pressure (60/40)
- Fast pulse (>100)
3 main causes of circulatory shock
- Hypovolaemic
- Septic (infections)
- Cardiogenic
also some other less important but possible causes
example of hypovolaemic shock
- Rib penetrates spleen and causes major bleed (bleed = haemorrhage)
- Systemic (arterial) blood pressure normal for a small period of time, but then as blood flows out of damaged spleen less blood is present in other vessels-> vessels collapse as they have no blood in them
- eventually there is less blood in inferior vena cava which also collapses
- If inferior vena cava has no blood in it then venous pressure falls to virtually zero
- Now almost no blood enters the right side of the heart
- Now very little blood goes through lungs
- Now very little blood goes to brain and rest of body
- Systemic blood pressure now drops
- Carotid sinuses sense lower blood pressure
- Carotid sinuses upregulate the sympathetic nervous system-> various signs (in addition to low blood pressure)
- rapid breathing, fast heart rate, pale sweaty skin
In hypovolaemic shock (circulatory shock) what does low blood pressure and a high pulse reflect
(relationship between 2)
- Low blood pressure - severe reduction in amound of blood in circulation
- High pulse - physiological response to low blood pressure
what happens in severe septic shock
muscle of heart, just like muscle in vessels, also loses it’s tone - may then get slow heart = bradycardia
septic shock
infection in blood causing genergalised vasodilation and shock
complications of shock - organ damage
Key LO
1.Brain injury (ischaemic infarction of brain tissue) - initially reversiable but then permanent
2.Decreased perfusion of kidneys à initially reversible, then more severe (ischaemic necrosis of renal tubules)
3.Others…
