Circulation Pathology Flashcards
Where are platelets produced?
Bone marrow
What is the precursor cell of platelets?
Megakaryocytes
Production of megakaryocytes
Megakaryocytes in the bone marrow undergo nuclear division but not cell division so we get a huge cell with many nuclei.
Platelets bud off as fragments from cytoplasmic extensions.
Define coagulaiton
Solidification of blood
What is the role of platelets?
Trauma to the vessel causes the exposure of platelets to interstitial collagen.
Platelets adhere together to try to form a bridge to close the gap/heal the trauma. platelets will clot (clump together) to plug the hole in the blood vessel and stop the bleeding.
What are the two types of coagulation?
Thrombus formation
Clot formation
What component of platelets allow the, to adhere to interstitial collagen?
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
What does a thrombus consist of?
Platelets and a mesh like network of fibrin strands
What is thrombosis?
Thrombosis is the process of thrombus formation which occurs in the flowing blood
Steps in thrombus formation
1)Constriction of the blood vessel
2) Formation of a temporary “platelet plug.”
3) Activation of the coagulation cascade. - clotting factors mainly proteins made by the liver
4) Formation of “fibrin plug” or the final clot.
What colour is a thrombus?
Pale cream coloured
What does a clot consist of?
A clot consists of a network of fibrin strands and red blood cells
Clot formation
- Blood leaks out of a vessel and becomes stationary (or stagnant)
- With the stagnant blood, sitting next to the interstitial collagen, the clotting cascade is activated
Where are key clotting factors produced?
Many are produced in the liver but also by endothelial cells
What does an amplification system result in?
Thrombin production
What does thrombin do?
Converts fibrinogen into insoluble fibrin
What is fibrinogen?
A soluble protein present in blood plasma, from which fibrin is produced by the action of the enzyme thrombin.
What is fibrin?
An insoluble protein that is produced in response to bleeding and is the major component of the blood clot.
What does fibrin form?
Mesh of strands
Where is fibrinogen made and found?
Made: liver
Found: Blood plasma
What does the clotting cascade do?
Lead to the production of thrombin from prothrombin
What are the steps in the clotting cascade?
- Damage to tissue factor
- Prothrombin is converted to thrombin
- Fibrinogen is converted to fibrin by thrombin
What does trauma lead to?
Exposure of interstital collagens (collagens in connective tissue between structures)
Exposure of a molecule called Tissue factor (TF)
What is tissue factor?
A transmembrane glycoprotein that functions as the primary cellular initiator of blood coagulation.
What is the aftermath of trauma?
- Trauma results in defects in vessels
- Blood leaks out
- Plasma clotting factors can now be activated as they contact interstitial collagens
In addition to this - tissue factor is released from smooth muscle cells when you get the cut in the vessel.
What happens in any trauma that causes bleeding?
Vasoconstriction helps reduce 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
What is granulation tissue and what grows in them?
New vessels can grow into area of wound.
These new vessels are called granulation tissue.
The capillaries that grow in (granulation tissue) can oxygenate the area of the wound and keep it alive.
Many clotting factors are serine proteases, what does this mean?
They have a serine amino acid in them and they cleave other clotting factors to form active molecules.
What part of the artery contains plasma?
Lumen of artery contains plasma
What does plasma consist of?
Water, numerous proteins and other molecules, clotting factors
What is serum?
Plasma without clotting factors
Give an example of haemostasis (stopping bleeding) in normal skin with a wound
- Vessel in skin is surrounded by collagen
- Trauma to skin disrupts one side of vessel
- Blood, including red blood cells, leaks out
- The clotting system is activated by collagen and by the stagnant blood, forming a clot
- This may not work perfectly and the wound may continue to bleed
- The vessel then constricts to decrease blood loss
- A platelet and fibrin thrombus forms to bridge the gap between the ends of the vessel adjacent to flowing blood
- The skin stops bleeding and haemostasis has been achieved
When does physiological thrombosis occur?
Normal after a cut or injury
When does pathological thrombosis occur?
In absence of cut or traumatic injury
What does Virchow’s triad describe?
Three factors that contribute to the development of venous thrombosis
What are the main causes of thrombosis according to Virchow’s triad?
Changes in the intimal surface of a vessel
Changes in the pattern of blood flow
Changes in the blood constituents
What is an example of a change in the intimal surface of a vessel that causes thrombosis?
Atheroma lipid coming onto surface
Smoking cigarettes increases the stickiness of platelets
Stickier platelets make it more likely that a thrombosis occurs
What is an example of a change in the pattern of blood flow that causes thrombosis?
A bulge of atheroma changing the blood flow
What is an example of a change in the blood constituents that causes thrombosis?
Smoking making it more likely that platelets aggregate
How does smoking change the pattern of blood flow?
- Smoking predispose to atheroma in the coronary arteries
- Atheroma is beginning to narrow down the lumen of the blood vessels causing abnormal blood vessel shape leading to an abnormal blood flow - flow can become both slow or turbulent
Define ischaemia
Insufficient supply of blood to an organ or tissue, usually as a result of narrowing or blockage of an artery.
Define anoxia
An absence of oxygen supply to an organ’s tissues although there is adequate blood flow to the tissue.
Define hypoxia
A decrease of oxygen to the tissue in spite of adequate blood flow to the tissue.
Define necrosis
The death of most or all of the cells in an organ or tissue due to disease, injury, or failure of the blood supply.
Define infarction
Obstruction of the blood supply to an organ or region of tissue, typically by a thrombus or embolus, causing local death of the tissue.
Give an example of infarction
Myocardial infarction (MI), commonly known as a heart attack, is an infarction of the heart, causing some heart cells to die.
Give an example of necrosis
Avascular necrosis occurs when blood flow to your bone tissue is blocked.
Lack of blood flow to your bones causes them to break down and eventually die.
Hip necrosis is the most common form of avascular necrosis.
Give an example of hypoxia
Low amounts of oxygen in the blood (hypoxemia) can lead to hypoxemic hypoxia, the most common cause of hypoxia.
Give an example of ischaemia
Plaques made up mostly of cholesterol build up on your artery walls and restrict blood flow. Atherosclerosis is the most common cause of myocardial ischemia.
How does ischaemia lead to hypoxia?
- Complete obstruction of an artery caused by a thrombus leads to no flow beyond blockage.
- Partial obstruction leads to decreased flow beyond blockage.
- Tissue supplied by this artery receives less blood flow.
What can tissues can tolerate ischaemia for extended periods?
Theskin and skeletal muscle
What tissues are sensitive to ischaemia?
Renal cortical cells are the most sensitive to ischemia
What does a coronary artery thrombosis cause?
Infarct in heart
What does a cerebral artery thrombosis cause?
Infarct in brain
What does a mesenteric artery thrombosis cause?
Infarct in gut
What is an embolism?
A blocked artery caused by a foreign body, such as a blood clot or air bubble
Where are most emboli derived from?
Thrombi or clots, they break off and go elsewhere in the circulation
What is a thromboembolism?
Obstruction of a blood vessel by a blood clot that has become dislodged from another site in the circulation.
What is the most common example of a thromboembolism?
Pulmonary embolism
What is a pulmonary embolism?
A pulmonary embolism often happens when part of the blood clot dislodges itself from your leg and travels up to your lungs, causing a blockage.
How does a 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 gets pulmonary infarct
What is a marrow embolism?
Fracture in leg
Marrow enters ruptured vein
Marrow embolises to lung vessels
What is an air embolism?
Knife wound to neck
Air enters vein
Air embolises to heart
When injecting the patient, what must the injection never have and why?
Must never have air
Can lead to air embolism
Define circulatory shock
Profound circulatory failure causing poor perfusion of vital organs.
What is shock in practice?
In practice shock = low blood pressure and its physiological consequences.
What are the two things seen in shock?
Low blood pressure <90/60mmHg
Fast heart beat >100 bpm
What are the three main causes of circulatory shock?
Hypovolaemic
Septic
Cardiogenic
What is hypovoloaemic shock?
Shock enduced by a low fluid volume of blood
What are the two types of hypovolemic shock?
Non-hemorrhagic
Hemorrhagic
What is non-hemorrhagic hypovolemic shock?
Not caused from bleeding
What is cardiogenic shock?
The inability of the heart to pump sufficient blood for the needs of the body.
What is septic shock
Infection in blood causing generalised vasodilation and shock
What is the physiological response to low blood pressure?
Faster pulse
How does body detect blood pressure and oxygen?
Carotid body and sinus on right side
Bifurcation (splitting) of artery into internal and external arteries
How do carotid bodies detect blood pressure?
The two carotid sinuses respond to blood pressure
If blood pressure drops - carotid sinuses “sense” and respond by nerve signals to the brain stem.
The brain stem tells the heart to pump harder and faster via nerve signals (sympathetic nervous system)
What is the normal blood pressure?
- Enough blood in system (5L in adult)
- Smooth muscle in vessels having correct tone
- Heart pumping blood
How does blood in vessels affect blood pressure?
No blood in vessels causes it to collapse and blood pressure becomes low then unrecordable
How does the tone of smooth muscles affect blood pressure?
If smooth muscle tone is decreased the vessel will dilate, if enough vessels are affects then blood pressure.
How does the heart pumping blood affect blood pressure?
If heart does not pump enough blood then blood pressure will fall
What is normal blood pressure?
120/80 mmHg
