Cardiovascular Disease Flashcards
Define
Ischaemic Stroke
Stroke caused by occlusion of a blood vessel by thrombus
Define
Cerebral ischaemia
a flow of blood to the brain that is insufficient to meet its metabolic demands, leading to loss of function and cell death
Define
Thrombus
a blood clot formed in situ within the vascular system of the body and impeding blood flow
Define
Embolic ischaemic stroke
Stroke cause by embolism in body that travels to the brain
Define
Thrombotic ischaemic stroke
Stroke caused by a thrombus growing and eventually blocking a blood vessel
Define
Haemorrhagic stroke
Stroke caused by the rupture of a blood vessel
Define
Subarachnoid haemorrhagic stroke
Stroke caused by bleeding in the space around the brain
Define
Intracerebral haemorrhagic stroke
Stroke caused by bleeding in the brain tissue itself
Define
Tissue plasminogen activator (tPA)/clot buster
a protein involved in the breakdown of blood clots
Define
Mechanical thrombectomy
the interventional procedure of removing a blood clot (thrombus) from a blood vessel
Define
Reperfusion
the action of restoring the flow of blood to an organ or tissue, typically after a heart attack or stroke.
Define
Cortical infarct
a small localized area of dead tissue involving the cortical gray matter resulting from failure of blood supply
Define
Bregma position
the anatomical point on the skull at which the coronal suture is intersected perpendicularly by the sagittal suture
Define
Excitotoxicity
the pathological process by which neurons are damaged and killed by the overactivations of receptors for the excitatory neurotransmitter glutamate, such as the NMDA receptor and AMPA receptor
Define
Amnion Epithelial Cells (hAEC)
a subset of placental-derived stem cells that display plasticity and immunomodulation, and possess advantages over the other populations of stem cell-like cells in the placental tissues
Define
Stem cell-derived exosomes
nano-sized vesicle secreted from cells that contains any of various biomolecules, such as proteins or nucleic acids
Definition
Stroke caused by occlusion of a blood vessel by thrombus
Ischaemic Stroke
Definition
a flow of blood to the brain that is insufficient to meet its metabolic demands, leading to loss of function and cell death
Cerebral ischaemia
Definition
a blood clot formed in situ within the vascular system of the body and impeding blood flow
Thrombus
Definition
Stroke cause by embolism in body that travels to the brain
Embolic ischaemic stroke
Definition
Stroke caused by a thrombus growing and eventually blocking a blood vessel
Thrombotic ischaemic stroke
Definition
Stroke caused by the rupture of a blood vessel
Haemorrhagic stroke
Definition
Stroke caused by bleeding in the space around the brain
Subarachnoid haemorrhagic stroke
Definition
Stroke caused by bleeding in the brain tissue itself
Intracerebral haemorrhagic stroke
Definition
a protein involved in the breakdown of blood clots
Tissue plasminogen activator (tPA)/clot buster
Definition
the interventional procedure of removing a blood clot (thrombus) from a blood vessel
Mechanical thrombectomy
Definition
the action of restoring the flow of blood to an organ or tissue, typically after a heart attack or stroke.
Reperfusion
Definition
a small localized area of dead tissue involving the cortical gray matter resulting from failure of blood supply
Cortical infarct
Definition
the anatomical point on the skull at which the coronal suture is intersected perpendicularly by the sagittal suture
Bregma position
Definition
the pathological process by which neurons are damaged and killed by the overactivations of receptors for the excitatory neurotransmitter glutamate, such as the NMDA receptor and AMPA receptor
Excitotoxicity
Definition
a subset of placental-derived stem cells that display plasticity and immunomodulation, and possess advantages over the other populations of stem cell-like cells in the placental tissues
Amnion Epithelial Cells (hAEC)
Definition
nano-sized vesicle secreted from cells that contains any of various biomolecules, such as proteins or nucleic acids
Stem cell-derived exosomes
Approximately how many strokes occur in Australia per year?
~60,000
True or False:
Stroke is Australia’s fifth leading cause of death
False
Stroke is Australia’s third leading cause of death
What age bracket do 50% of strokes occur in?
45-75 years old
Are men or women more likely to die after a stroke?
Women are morelikely to die after a stroke than men
True or False:
More women die from stroke than from breast cancer
True
Do men or women suffer more strokes?
Men
True or False:
Stroke is considered a cardiovascular disease
True
True or False:
Stroke is the worst disease in Australia in terms of suffering and cost
True
What proportion of people who suffer a stroke die, become dependent and recover?
Death: 1/3
Dependency: 1/3
Recovery: 1/3
What percentage of stroke sufferers experience a recurrent stroke?
10%
Lack of what molecules/nutrients cause neuronal cell death during a stroke?
Oxygen
Glucose
Which important molecule is strangely not stored in the brain?
Glucose
What are the two main types of stroke?
Ischaemic stroke
Haemorrhagic stroke
What are the two types of Ischaemic stroke?
Embolic
Thrombotic
What are the two types of haemorrhagic stroke?
Subarachnoid
Intracerebral
What is the most common major type of stroke?
Ischaemic (~85%)
What are the five biggest risk factors for ischaemic stroke?
Hypertension
Atrial fibrilation
Smoking
Diabetes
Age
True or False:
Hypertension is more likely to cause a heart attack than a stroke
False
Hypertension is more likely to cause a stroke than a heart attack
Why is time so critical in treating stroke?
Approximately 2 million neurons die every minute that a person is suffering a stroke and the average person will suffer a stroke for several hours resulting in significant neurological damage
What is the current treatment plan for Ischaemic stroke?
- Diagnose stroke type (MRI, CT scan)
- If stroke is ischaemic and occured under 4.5 hours ago, clot buster enzyme (tPA) will be injected (only 2-8% of patients satisfy this)
- High blood pressure treated
- Anticoagulants, antiplatelet drugs to thin the blood - if ischaemic)
- Osmotic agents (and elevate head) - if haemorrhagic
- Physiotherapy, speech therapy - ASAP
What is the only therapy currently available for stroke?
Clot buster enzyme (tPA)
Why is it important to treat high blood pressure after a stroke has occurred?
To prevent subsequent strokes
After 4.5 hours, what drugs are used to prevent further damage in ischaemic and haemorrhagic stroke?
Ischaemic - Anticoagulants and antiplatelt drugs to thin the blood
Haemorrhagic - Osmostic agents (& elevation of head)
When is clot buster (tPA) given to a patient?
When a CT scan indicates an ischaemic stroke and it is within 4.5 hours of onset
Why isn’t clot buster (tPA) given to patients after 4.5 hours of stroke onset?
Increased risk of haemorrhage
Why are people who have a stroke overnight often ineligible for tPA?
We often cannot be sure that the stroke begun within 4.5 hours prior to hospital presentation
What percentage of people who receive tPA benefit?
30%
What is the name of the procedure that involves physically removing a clot?
Mechanical thrombectomy
Mechanical thrombectomy is only performed in patients with occlusion of which vessels?
Large cerebral artery
When can a mechanical thrombectomy be performed?
Within 24 hours of stroke
Will patients eligible for tPA receive the tPA or mechanical thrombectomy first?
tPA first (unless contraindicated)
Why is mechanical thrombectomy only performed in patients with occlusion of large cerebral artery?
The stent can’t get into small vessels
How can hypothermia be used to manage stroke?
Hypothermia slows cellular processes, decreasing neuronal death and the size of the infarct
Why have patients own bone marrow stem cells shown more promise than neural stem cells in overcoming stroke damage?
Using the patients own stem cells ensures that the cells won’t be targetted by the host immune system. The bone marrow stem cells adminstered via IV release a cocktail of chemicals into the blood which trigger growth and repair of neurons in the brain
What are the drawbacks of using stem cell therapy to treat stroke damage?
It takes a long time to prepare and administer stem cells
Stroke causes most neurons to die via which process? Why don’t we focus on this process in research?
Most cells die due to excitotoxicity that occurs in the first few hours. However, since most patients don’t present to the hospital until hours after onset so most current research focuses on the subsequent neuroinflammation
Approximately what percentage of neurons die due to neuroinflammation?
30-40%
What is the main mechanism by which hAECs may improve stroke outcome?
Immunomodulatory properties since this process occurs in the first few days following stroke
- Decreasing immune cells infiltrating the brain
- Decreasing cerebral infarct damage
What are the potential consequneces of hAEC IV administration?
Stem cells can clump during IV administration and get stuck in lungs
How do we overcome the limitations of hAEC IV administration?
Isolated stem cell-derived exosomes which contain the cocktail of repair chemicals which are able to pass through the lungs and blood-brain barrier without issue
Why are stem cell-derived exosomes more promising for improving stroke outcomes than regular stem cells?
- They are able to pass through lungs and BBB
- Can inject higher dose
- Ready to inject within minutes
Define
Abdominal aortic aneurysm
an enlarged area in the lower part of the major vessel that supplies blood to the body (aorta)
Define
Aneurysm
an excessive localized swelling of the wall of an artery.
Define
Apo B-100
a protein that plays a role in moving cholesterol around your body. It is a form of low density lipoprotein (LDL)
Define
Apo-A-I
a structural and functional protein that constitutes approximately 70% of the protein in high density lipoprotein (HDL)
Define
Apoprotein
a protein which together with a prosthetic group forms a particular biochemical molecule such as a hormone or enzyme.
Define
Astrocytosis
an abnormal increase in the number of astrocytes due to the destruction of nearby neurons from central nervous system (CNS) trauma, infection, ischemia, stroke, autoimmune responses or neurodegenerative disease
Define
Atherosclerosis
a disease of the arteries characterized by the deposition of fatty material on their inner walls.
Define
Autologous blood injection model
involves drawing a small volume of venous blood from the patient and re-injecting this in and around the tendon origin
Define
Axonal sprouting
a process where fine nerve processes – sprouts – grow out from the intact axons to reinnervate denervated muscle fibers
Define
C-reactive protein (CRP)
a protein made by your liver. It’s sent into your bloodstream in response to inflammation.
Define
Cerebral aneurysm
a bulging, weakened area in the wall of an artery in the brain, resulting in an abnormal widening, ballooning, or bleb
Define
Cholesterol
a compound of the sterol type found in most body tissues. This molecule and its derivatives are important constituents of cell membranes and precursors of other steroid compounds, but a high proportion in the blood of low-density lipoprotein (which transports cholesterol to the tissues) is associated with an increased risk of coronary heart disease.
Define
Chylomicrons
a droplet of fat present in the blood or lymph after absorption from the small intestine.
Define
Congenital aneurysm
a weakness in the blood vessel wall that is present from birth
Define
Dissecting aneurysm
An aneurysm in which the wall of an artery rips longitudinally. This occurs because bleeding into the weakened wall splits the wall.
Define
Endothelin
peptides with receptors and effects in many body organs. They constricts blood vessels and raises blood pressure
Define
Endovascular coiling
a minimally invasive technique where a catheter is passed through the groin up into the artery containing the aneurysm
Define
Familial hypercholesterolaemia
a common life-threatening genetic condition that causes high cholesterol
Define
Foam cells
a type of macrophage that localize to fatty deposits on blood vessel walls, where they ingest low-density lipoproteins and become laden with lipids, giving them a foamy appearance
Define
Fusiform aneurysm
a type of aneurysm that bulges or balloons out on all sides of the blood vessel
Define
Giant aneurysm
aneurysms greater than 25 mm in diameter14 and represent 5% of all intracranial aneurysms
Define
High density lipoproteins (HDL)
lipoprotein of blood plasma that is composed of a high proportion of protein with little triglyceride and cholesterol and that is correlated with reduced risk of atherosclerosis
Define
Hyperlipidaemia
the presence of excess fat or lipids in the blood
Define
Ischemic penumbra
tissue surrounding an ischemic event that is ischemic but still viable
Define
LDL receptor
a mosaic protein of 839 amino acids that mediates the endocytosis of cholesterol-rich LDL
Define
Lipoproteins
any of a group of soluble proteins that combine with and transport fat or other lipids in the blood plasma.
Define
Low density lipoproteins (LDL)
a lipoprotein of blood plasma that is composed of a moderate proportion of protein with little triglyceride and a high proportion of cholesterol and that is associated with increased probability of developing atherosclerosis
Define
Lp(a)
a low-density lipoprotein variant containing a protein called apolipoprotein(a).
Define
Mannitol
an osmotic agent used to lower intracranial pressure
Define
PCSK9 inhibitors
a new class of drugs that lower LDL, or “bad,” cholesterol
Define
Photothrombotic stroke
aims to induce an ischemic damage within a given cortical area by means of photo-activation of a previously injected light-sensitive dye. Following illumination, the dye is activated and produces singlet oxygen that damages components of endothelial cell membranes, with subsequent platelet aggregation and thrombi formation, which eventually determines the interruption of local blood flow
Define
Plasminogen
the zymogen of plasmin, the major enzyme that degrades fibrin clots
Define
Reverse cholesterol transport
a multi-step process resulting in the net movement of cholesterol from peripheral tissues back to the liver first via entering the lymphatic system, then the bloodstream
Define
Saccular aneurysm
the most common type of brain aneurysm. They have a “neck” that connects the aneurysm to its main (“parent”) artery and a larger, rounded area called the dome
Define
Statins
a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs
Define
Subarachnoid hemorrhage
bleeding within the subarachnoid space, which is the area between the brain and the tissues that cover the brain
Define
Surgical clipping
to isolate an aneurysm from the normal circulation without blocking off any small perforating arteries nearby
Define
Thoracic aortic aneurysm
an aortic aneurysm that presents primarily in the thorax
Define
Venous thrombosis
a blood clot that starts in a vein
Define
Very low density lipoproteins (VLDL)
cholesterol that is produced in the liver and released into the bloodstream to supply body tissues with a type of fat (triglycerides)
Definition
an enlarged area in the lower part of the major vessel that supplies blood to the body (aorta)
Abdominal aortic aneurysm
Definition
an excessive localized swelling of the wall of an artery.
Aneurysm
Definition
a protein that plays a role in moving cholesterol around your body. It is a form of low density lipoprotein (LDL)
Apo B-100
Definition
a structural and functional protein that constitutes approximately 70% of the protein in high density lipoprotein (HDL)
Apo-A-I
Definition
a protein which together with a prosthetic group forms a particular biochemical molecule such as a hormone or enzyme.
Apoprotein
Definition
an abnormal increase in the number of astrocytes due to the destruction of nearby neurons from central nervous system (CNS) trauma, infection, ischemia, stroke, autoimmune responses or neurodegenerative disease
Astrocytosis
Definition
a disease of the arteries characterized by the deposition of fatty material on their inner walls.
Atherosclerosis
Definition
involves drawing a small volume of venous blood from the patient and re-injecting this in and around the tendon origin
Autologous blood injection model
Definition
a process where fine nerve processes – sprouts – grow out from the intact axons to reinnervate denervated muscle fibers
Axonal sprouting
Definition
a protein made by your liver. It’s sent into your bloodstream in response to inflammation.
C-reactive protein (CRP)
Definition
a bulging, weakened area in the wall of an artery in the brain, resulting in an abnormal widening, ballooning, or bleb
Cerebral aneurysm
Definition
a compound of the sterol type found in most body tissues. This molecule and its derivatives are important constituents of cell membranes and precursors of other steroid compounds, but a high proportion in the blood of low-density lipoprotein (which transports cholesterol to the tissues) is associated with an increased risk of coronary heart disease.
Cholesterol
Definition
a droplet of fat present in the blood or lymph after absorption from the small intestine.
Chylomicrons
Definition
a weakness in the blood vessel wall that is present from birth
Congenital aneurysm
Definition
An aneurysm in which the wall of an artery rips longitudinally. This occurs because bleeding into the weakened wall splits the wall.
Dissecting aneurysm
Definition
peptides with receptors and effects in many body organs. They constricts blood vessels and raises blood pressure
Endothelin
Definition
a minimally invasive technique where a catheter is passed through the groin up into the artery containing the aneurysm
Endovascular coiling
Definition
a common life-threatening genetic condition that causes high cholesterol
Familial hypercholesterolaemia
Definition
a type of macrophage that localize to fatty deposits on blood vessel walls, where they ingest low-density lipoproteins and become laden with lipids, giving them a foamy appearance
Foam cells
Definition
a type of aneurysm that bulges or balloons out on all sides of the blood vessel
Fusiform aneurysm
Definition
aneurysms greater than 25 mm in diameter14 and represent 5% of all intracranial aneurysms
Giant aneurysm
Definition
lipoprotein of blood plasma that is composed of a high proportion of protein with little triglyceride and cholesterol and that is correlated with reduced risk of atherosclerosis
High density lipoproteins (HDL)
Definition
the presence of excess fat or lipids in the blood
Hyperlipidaemia
Definition
tissue surrounding an ischemic event that is ischemic but still viable
Ischemic penumbra
Definition
a mosaic protein of 839 amino acids that mediates the endocytosis of cholesterol-rich LDL
LDL receptor
Definition
any of a group of soluble proteins that combine with and transport fat or other lipids in the blood plasma.
Lipoproteins
Definition
a lipoprotein of blood plasma that is composed of a moderate proportion of protein with little triglyceride and a high proportion of cholesterol and that is associated with increased probability of developing atherosclerosis
Low density lipoproteins (LDL)
Definition
a low-density lipoprotein variant containing a protein called apolipoprotein(a).
Lp(a)
Definition
an osmotic agent used to lower intracranial pressure
Mannitol
Definition
a new class of drugs that lower LDL, or “bad,” cholesterol
PCSK9 inhibitors
Definition
aims to induce an ischemic damage within a given cortical area by means of photo-activation of a previously injected light-sensitive dye. Following illumination, the dye is activated and produces singlet oxygen that damages components of endothelial cell membranes, with subsequent platelet aggregation and thrombi formation, which eventually determines the interruption of local blood flow
Photothrombotic stroke
Definition
the zymogen of plasmin, the major enzyme that degrades fibrin clots
Plasminogen
Definition
a multi-step process resulting in the net movement of cholesterol from peripheral tissues back to the liver first via entering the lymphatic system, then the bloodstream
Reverse cholesterol transport
Definition
the most common type of brain aneurysm. They have a “neck” that connects the aneurysm to its main (“parent”) artery and a larger, rounded area called the dome
Saccular aneurysm
Definition
a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs
Statins
Definition
bleeding within the subarachnoid space, which is the area between the brain and the tissues that cover the brain
Subarachnoid hemorrhage
Definition
to isolate an aneurysm from the normal circulation without blocking off any small perforating arteries nearby
Surgical clipping
Definition
an aortic aneurysm that presents primarily in the thorax
Thoracic aortic aneurysm
Definition
a blood clot that starts in a vein
Venous thrombosis
Definition
cholesterol that is produced in the liver and released into the bloodstream to supply body tissues with a type of fat (triglycerides)
Very low density lipoproteins (VLDL)
What are the most common areas for an aneurysm to form?
Along the aorta and in the brain
What causes an aneurysm?
- a weakness in the blood vessel wall that is present from birth (congenital aneurysm)
- High blood pressure (hypertension) - weakening of blood vessels
- Previous aneurysm: increased likelihood to have another.
- Race: African Americans are more likely than Caucasians to have a subarachnoid hemorrhage.
- Fatty plaques (atherosclerosis) resulting in a weakness of the blood vessel wall
- Inherited diseases that may result in weaker than normal blood vessel walls
- Gender. Women are more likely to develop a brain aneurysm or to suffer a subarachnoid hemorrhage.
- Trauma, such as a crush injury to the chest
- The sexually transmitted infection (STI) syphilis, if untreated, targeting the aorta and weakening its walls
- Polycystic kidney disease increasing the risk of cerebral aneurysm
- Very occasionally, an infection targeting and weakening a section of blood vessel.
- The cause sometimes remains unknown.
What is the current theory on why women are more likely to develop a brain aneurysm?
Oestrogen is protective in the cardiovascular system so when women have a dramatic drop in oestrogen following menopause they are at higher risk
What are the three main types (location) of aneurysms?
Cerebral aneurysm
Thoracic aortic aneurysm
Abdomincal aortic aneurysm
What are the symptoms of an unruptured cerebral aneurysm?
An unruptured cerebral aneurysm may have no symptoms related to it at all and may be discovered incidentally.
What are the symptoms of an ruptured cerebral aneurysm?
Symptoms of a ruptured cerebral aneurysm include severe headache with rapid onset, neck pain and stiffness, increasing drowsiness, paralysis, seizures, impaired speech and visual problems.
What is the most common type of cerebral aneurysm?
Saccular (80-90%)
What is the fatality and disability rate of rupture cerebral aneurysms?
Ruptured brain aneurysms are fatal in about 40% of cases. Of those who survive, about 66% suffer some permanent neurological deficit.
What age range are brain aneurysms most prevalent?
35-60
What are the four main types (shape) of aneurysms?
Saccular
Fusiform
Giant
Dissencting
What type is this aneurysm?
Saccular aneurysm
What type is this aneurysm?
Fusiform aneurysm
What percentage of aneurysms do not rupture during the course of a person’s lifespan?
50-80%
What is the most damaging type of aneurysm?
Dissecting aneurysm
How does a dissecting aneurysm occur?
- The wall of an artery rips (dissects) longitudinally
- Occurs because bleeding into the weakened wall splits the wall.
- Creates a false lumen
The prevalence of AA sharply increases with increasing _____
The prevalence of AA sharply increases with increasing age
What is the mortality rate of an aortic aneurysm rupture?
~80%
Surgical repair of ruptured AA has a mortality of around ___%.
Surgical repair of ruptured AA has a mortality of around 50%.
What things should be considered when deciding whether or not to treat an unruptured aneurysm?
- Risk of Hemorrhage—Is it probable or not that the aneurysm will rupture?
- Size and Location
- Age and Health of Patient
- Family History—Is there a family history? Have any of those aneurysms ruptured?
- Surgical Risks
What are the two types of surgical treatments of unruptured aneurysms?
Surgical clipping
Endovascular coiling
What drug is used as an osmotic agent following haemorragic stroke?
Mannitol
What is Mannitol used for strokes?
Used to reduce edema, intracranial pressure following haemorrhagic stroke
How does Mannitol reduce intracranial pressure?
- Used to raise the serum osmolarity
- Plasma osmotic pressure is increased relative to cerebrospinal fluid.
- Causes an increase in osmotic pressure in the serum and water follows from tissue into blood.
What are the adverse effects of Mannitol?
- About 10% of patients will develop edema
- Can be very dangerous depending on site in brain
Why do 10% of patients given Mannitol develop edema, the very condition Mannitol is used to treat?
If the vessels or BBB are leaky, the Mannitol will get into the brain tissue causing fluid to follow
Why is one animal model for stroke not enough?
Mimicking all aspects of human stroke in one animal model is not feasible because stroke in humans is a heterogeneous disorder with a complex pathophysiology.
Which animal models are used for ischaemic stroke?
Middle cerebral artery occlusion
Photothrombotic stroke
Endothelin-1 stroke
Which animal models are used for haemorragic stroke?
Autologous blood injection
Endovascular puncture
What are the pros and cons of middle cerebral artery occlusion as an animal model?
Pros:
- Mimics human stroke ie MCAO
- Reperfusion and duration is controlled
- Blood flow is measured
- Most common mode
Cons:
- Variable infarct damage
- Invasive surgery
What are the pros and cons of photothrombotic stroke?
Pros:
- Induces a thrombus
- Minimal surgical intervention
- Highly reproducible infarct damage
Cons:
- Little or no ischemic penumbra (unlike humans)
- Unable to measure blood flow
How does the middle cerebral artery occlusion animal model work?
A silicone-coated filament is inserted into the external carotid artery and pushed up into the brain until the laser doppler probe indicates a drop in blood flow meaning the filament is blocking the middle cerebral artery
How does a photothrombotic stroke work?
A photosensitive dye is administered to the animal. The skin covering the skull is removed and a bright light is positioned over the skull. The light and dye cause free radical formation which damages endothelial cells leading to platelet aggregation and subsequent clots
What are the pros and cons of the endothelin model?
Pros:
- Conscious model of stroke
- Reproducible infarct damage
- Low mortality
Cons:
- Induces astrocytosis and facilitates axonal sprouting
- Unable to measure blood flow changes
- Lacks BBB breakdown
What are the pros and cons of the autologous blood injection model?
Pros:
- Blood is injected into the striatum to establish a haemtoma
- Widely used model
- Good reproducibility and relevant to ICH patients
Cons:
- Does not simulate blood vessel rupture
What are the pros and cons of the endovascular puncture model?
Pros:
- Closely mimics SAH in the clinic
- Blood flow can be measured
Cons:
- Invasive surgery
How does the endovascular puncture model work?
Similar to the middle cerebral artery occlusion model except the filament punctures the blood vessel causing a bleed
How is fat transported around the cardiovascular system?
As a lipoprotein
Lipid (hydrophobic core) and apoprotein (hydrophillic coat)
What are the four main types (in decreasing size) of lipoprotein?
Chylomicrons
VLDL
LDL
HDL
What ligand does VLDL and LDL have that allows LDL reuptake?
Apo B-100
True or False:
Due to size VLDL, but not LDL, can easily penetrate the vascular endothelium
False
Due to size LDL, but not VLDL, can easily penetrate the vascular endothelium
Which molecule is Lp(a) similar to and competes with?
Plasminogen
What is the exogenous pathway of lipoprotein transport in the blood?
What is the endogenous pathway of lipoprotein transport?
Which cells synthesise LDL receptors?
Liver and vascular smooth muscle cells
How does the immune system impact atherosclerosis?
Vascular inflammation drive atherosclerosis
- Vascular cholesterol uptake by LDL receptors
- Excess LDL infiltrates artery
- Oxidised LDL induces adhesion molecule expression on endothelium
- Oxidised LDL phagocytosed by macrophages (now called foam cells)
- Monocyte recruitment into arterial wall
- Adhesion molecules facilitate entry
- Differentiate into macrophages
- Macrophages release mediators creating inflammatory milieu
- Inflamm/immune cell surveillance
- T cells infiltrate….
- Activated T cells produce Th1cytokines e.g. IFNγ, IL-1β, IL-6, TNF
- Amplification of vascular inflammation
- T regs oppose, release IL-10, TGF-β
What is the main vascular and circuating inflammatory biomarkers of atherosclerosis?
C-reactive protein (CRP)
Why is CRP a good biomarker for atherosclerosis?
- Acute phase protein synthesised in liver
- Stimulated by IL-6 from inflamm cells
- Binds to surface of dying cells; promotes phagocytosis
- Predictive of inflammation/CVD
- Informs on statin therapy
Describe the steps from a healthy epithelium to a ruptured fibrous cap seen in atherosclerosis
What make up fatty streaks?
Oxidised LDL taken up by macrophages, known as foam cells
Why do fibrous caps form?
Formation of fibrous cap trying to stabilise underlying lipid core
How does inflammatory signalling affect the collagen cap?
↓ collagen synthesis (T cell driven)
↑ degradation due to MMP released from macrophages
↑ tissue factor released from macrophages (thrombosis potential)
What are the chronic drug treatments for atherosclerosis?
Reduce lipid/plaque/inflamm burden
- Lipid-lowering drugs e.g. Statins, new drugs
- Anti-platelets
- Anti-coagulants (not covered here- phew!)
What happens to cholesterol hepatic synthesis and LDL-R transcription as intracellulat cholesterol levels increase?
They both decrease
How are hyperlipidaemias treated?
- consider CV status and risk factors
- secondary to other disease?
- treat disease first- eg diabetes, hypertension
- dietary / lifestyle modification BEFORE any drug treatment
Rationale:
- reduce progression of atherosclerosis and improve survival in patients with established CV disease
- reduce premature cardiac morbidity and mortality in people at high risk of CV disease
What are the two major drug types for treating hypercholesterolemia?
Statins
PCSK9 inhibitors
Which enzyme do statins target?
HMG-CoA reductase
Resposible for the rate limiting step in cholesterol synthesis where HMG-CoA is converted to cholesterol
What is the mode of action of statins?
- block cholesterol synthesis in liver (competitive enzyme inhibitor)
- reduces endogenous cholesterol in hepatocytes which promotes increased expression of LDL receptors on hepatocytes (i.e. disrupt feedback regulation)
- Leads to increased LDL plasma clearance
- Many effects unrelated to ↓LDL such as improved endothelial function, plaque stabilisation
- Lipoprotein profile: ↓↓LDL, ↓TG, HDL
What are the clinical uses of statins?
- primary prevention cardiovascular disease (high risk with elevated cholesterol)
- High risk CHD (with/without elevated chol)
- secondary prevention of myocardial infarction & stroke (symptomatic)
What are the potential side-effects of statins?
GI disturbance
diabetes risk
Memory loss (reversible)
What can CRP levels tell us about a patients response to statins?
Patients who have low CRP levels after statin therapy have better clinical outcomes
What is PCSK9?
circulating serine protease (enzyme) that binds to LDL rec; facilitates lysosomal degradation → LDL rec recycling to cell surface
reduces LDL clearance; elevating circulating LDL
What molecules are used to inhibit PCSK9?
Antibodies
How do statins upregulate LDL receptors and LDL clearance?
By inhibiting HMG-CoA reductase and decreasing intracellular cholesterol
Without ________ attached, the LDL receptor is recycled to the cell surface, and can continue to clear LDL particles
Without PCSK9 attached, the LDL receptor is recycled to the cell surface, and can continue to clear LDL particles
How does PCSK9 prevent recycling of LDL receptors?
PCSK9 ‘tags’ LDL receptor, resulting in its degradation in the lysosome
What are the downsides of PCSK9 inhibitors?
Can’t be administered orally (injections only)
Expensive
Define
Allocative efficiency
an output level where the Price equals the Marginal Cost (MC) of production. Concerned with efficient distribution of available resources and potential opportunity costs.
Define
Technical efficiency
the effectiveness with which a given set of inputs is used to produce an output. Looks at efficient management of single condition and considers cost-effectiveness
Define
Cost-benefit analysis
a systematic approach to estimating the strengths and weaknesses of alternatives used to determine options which provide the best approach to achieving benefits while preserving savings. Does not consider the potential health benefits
Define
Cost-effectiveness analysis
a form of analysis that compares the relative costs and outcomes (effects) of different courses of action.
Define
Cost-utility analysis
a form of analysis used to guide procurement decisions. Net costs/net change in QALYs
Define
Quality-Adjusted Life Year (QALY)
a generic measure of disease burden, including both the quality and the quantity of life lived
Define
Dominated intervention
When a new intervention is both clinically inferior and increases costs
Define
Dominant intervention
When a new intervention is both clinically superior and cost saving
Define
Angina
chest pain or discomfort caused when your heart muscle doesn’t get enough oxygen-rich blood
Define
Coronary heart disease (CHD)
occurs when a coronary artery clogs and narrows because of a buildup of plaque overtime
Define
Acute coronary syndrome (ACS)
a term used to describe a range of conditions associated with sudden, reduced blood flow to the heart
Define
Acute mycardial infarction (AMI)
the medical name for a heart attack.
Define
Troponin
a group of proteins found in skeletal and heart (cardiac) muscle fibers that regulate muscular contraction. Acts as a biomarker to help detect heart injury
Define
Stable angina
when a person has brief episodes of pain, squeezing, pressure, or tightness in the chest
Define
Heart failure
occurs when your heart muscle doesn’t pump blood as well as it should. Certain conditions, such as narrowed arteries in your heart (coronary artery disease) or high blood pressure, gradually leave your heart too weak or stiff to fill and pump efficiently
Define
ST-elevation myocardial infarction (STEMI)
a very serious type of heart attack during which one of the heart’s major arteries (one of the arteries that supplies oxygen and nutrient-rich blood to the heart muscle) is blocked
Define
Non-ST-elevation myocardial infarction (NSTEMI)
A type of heart attack that is less damaging than its counterpart involving no elevation of the ST segment
Define
Myoglobin
an iron- and oxygen-binding protein found in the skeletal muscle tissue of vertebrates in general and in almost all mammals
Define
Creatine kinase (CK)
an enzyme found in the heart, brain, skeletal muscle, and other tissues. Increased amounts of this molecule are released into the blood when there is muscle damage
Define
Natriuretic peptides
a peptide that induces natriuresis, which is the excretion of sodium by the kidneys
Define
Atrial natriuretic peptides (ANP)
a natriuretic peptide hormone secreted from the cardiac atria that in humans is encoded by the NPPA gene. The main function of this molecule is causing a reduction in expanded extracellular fluid (ECF) volume by increasing renal sodium excretion
Define
Brain natriuretic peptides (BNP)
a hormonse secreted by cardiomyocytes in the heart ventricles in response to stretching caused by increased ventricular blood volume. It is released from the ventricle of patients with heart failure.
Define
Nitric oxide (NO)
a mediator of vasodilation in blood vessels
Define
Dyspnea
the medical term for shortness of breath
Define
HFrEF
The heart muscle does not contract effectively, and therefore less oxygen-rich blood is pumped out to the body
Define
HFpEF
a clinical syndrome in which patients have clinical features of heart failure in the presence of normal or near-normal left ventricular ejection fraction, usually defined as ejection fraction at 50% or above
Definition
an output level where the Price equals the Marginal Cost (MC) of production. Concerned with efficient distribution of available resources and potential opportunity costs.
Allocative efficiency
Definition
the effectiveness with which a given set of inputs is used to produce an output. Looks at efficient management of single condition and considers cost-effectiveness
Technical efficiency
Definition
a systematic approach to estimating the strengths and weaknesses of alternatives used to determine options which provide the best approach to achieving benefits while preserving savings. Does not consider the potential health benefits
Cost-benefit analysis
Definition
a form of analysis that compares the relative costs and outcomes (effects) of different courses of action.
Cost-effectiveness analysis
Definition
a form of analysis used to guide procurement decisions. Net costs/net change in QALYs
Cost-utility analysis
Definition
a generic measure of disease burden, including both the quality and the quantity of life lived
Quality-Adjusted Life Year (QALY)
Definition
When a new intervention is both clinically inferior and increases costs
Dominated intervention
Definition
When a new intervention is both clinically superior and cost saving
Dominant intervention
Definition
chest pain or discomfort caused when your heart muscle doesn’t get enough oxygen-rich blood
Angina
Definition
occurs when a coronary artery clogs and narrows because of a buildup of plaque overtime
Coronary heart disease (CHD)
Definition
a term used to describe a range of conditions associated with sudden, reduced blood flow to the heart
Acute coronary syndrome (ACS)
Definition
the medical name for a heart attack.
Acute mycardial infarction (AMI)
Definition
a group of proteins found in skeletal and heart (cardiac) muscle fibers that regulate muscular contraction. Acts as a biomarker to help detect heart injury
Troponin
Definition
when a person has brief episodes of pain, squeezing, pressure, or tightness in the chest
Stable angina
Definition
occurs when your heart muscle doesn’t pump blood as well as it should. Certain conditions, such as narrowed arteries in your heart (coronary artery disease) or high blood pressure, gradually leave your heart too weak or stiff to fill and pump efficiently
Heart failure
Definition
a very serious type of heart attack during which one of the heart’s major arteries (one of the arteries that supplies oxygen and nutrient-rich blood to the heart muscle) is blocked
ST-elevation myocardial infarction (STEMI)
Definition
A type of heart attack that is less damaging than its counterpart involving no elevation of the ST segment
Non-ST-elevation myocardial infarction (NSTEMI)
Definition
an iron- and oxygen-binding protein found in the skeletal muscle tissue of vertebrates in general and in almost all mammals
Myoglobin
Definition
an enzyme found in the heart, brain, skeletal muscle, and other tissues. Increased amounts of this molecule are released into the blood when there is muscle damage
Creatine kinase (CK)
Definition
a peptide that induces natriuresis, which is the excretion of sodium by the kidneys
Natriuretic peptides
Definition
a natriuretic peptide hormone secreted from the cardiac atria that in humans is encoded by the NPPA gene. The main function of this molecule is causing a reduction in expanded extracellular fluid (ECF) volume by increasing renal sodium excretion
Atrial natriuretic peptides (ANP)
Definition
a hormonse secreted by cardiomyocytes in the heart ventricles in response to stretching caused by increased ventricular blood volume. It is released from the ventricle of patients with heart failure.
Brain natriuretic peptides (BNP)
Definition
a mediator of vasodilation in blood vessels
Nitric oxide (NO)
Definition
the medical term for shortness of breath
Dyspnea
Definition
The heart muscle does not contract effectively, and therefore less oxygen-rich blood is pumped out to the body
HFrEF
Definition
a clinical syndrome in which patients have clinical features of heart failure in the presence of normal or near-normal left ventricular ejection fraction, usually defined as ejection fraction at 50% or above
HFpEF
Who is the main funding contributer to Australian Healthcare?
Australian Federal Government (41%)
State and Territory Governments (27%)
Private (32%)
What are the key challenges of the Australian healthcare system?
- expense and affordability
- rising costs, driven by both volume (ageing population) and expensive technology
- goals:
- safety, quality and efficiency
- patient-centred healthcare
- value-based healthcare
What are the two types of efficieny in healthcare?
Allocative
Technical
What are the three types of health economic analyses?
Cost-benefit
Cost-effectiveness
Cost-utility
Which type of health economic analysis doesn’t consider health benefits?
Cost-benefit
If a disease has a utility weight of 0.8 and a person has lived with the disease for 2 years. What is the equivalent of how many years lived without disease?
1.6 years
What is the incremental cost-effectiveness ratio?
A line that divides the top right quadrant (net positive costs and net health gain) into two halfs. The line represents the points that $50,000 are spent per QALY. Beneath the line the benefits are worth the cost but above they are not
What type of interventions may be considered “dominated”?
Medications prescribed to incorrect patients
What type of interventions may be considered “dominant”?
Surgery
Vaccination
What are some acute examples of coronary heart disease?
Acute coronary syndrome
- Angina
- Acute myocardial infarction (AMI; heart attack)
What are some chronic examples of coronary heart disease?
Stable angina
Heart failure
Which layer of the heart tissue is vulnerable ischaemia?
Sub-endocardial zone
Which stage of a heart beat do coronary arteries fill?
Diastole
Where does the sub-endocardial zone receive blood from?
Balance of supply from coronary arteries and diffusion from left ventricle
What is the order of the acute coronary syndrome continuum?
Normal
Angina
ACS
NSTEMI
STEMI
What are the two groups that Acute coronary syndrome is split into based on ECG results?
- Patients with acute chest pain and persistent (>20 min) ST-segment elevations (STEMI)
- Patients with acute chest pain but no persistent ST-segment elevation (NSTEMI)
What does a STEMI ECG look like?
What is the difference between NSTEMI and STEMI in terms of vessel occlusion and thickness of infarct?
NSTEMI: Partial vessel occlusion and partial thickness infarct
STEMI: Complete vessel occlusion and full thickness infarct
Which biomarker is the best for indicating AMIs?
Cardiac toponin
Why isn’t myoglobin used as a cardiac biomarker?
It is detected in the blood after AMI and skeletal muscle injury
i.e. it is not selective
Where is creatine kinase found and why can it be used as a cardiac biomarker?
It is found in the heart and skeletal muscle. It can be used as a cardiac biomarker because the MB isoform is relatively heart-specific
When does troponin start to increase after AMI and how long is it abnormal for?
Detected 4-10 hours after AMI, peak at 12-48 hours, abnormal for 4-10 days
Which biomarkers are released from dying muscle?
Creatine kinase-MB
c-troponin
What causes the release of natriuretic peptides?
Atrial distension (ANP) and left ventricle stretch/stress (BNP)
BNP and N-terminal breakdown product (NT-proBNP) are biomarkers for what condition?
Heart failure
What are the causes of AMIs?
- Coronary artery occlusion- plaque build up +/- rupture
- Aortic valve problems
- Coronary artery aneurysms
- Electrical failure (arrhythmias)
- Illicit drugs (cocaine, amphetamine…)
- Anticancer drugs etc
- Increased risk, e.g. hypertension, diabetes
Which part of the heart does the infarct usually occur during a heart attack?
Usually left ventricle - thicker muscle
How is heart tissue repaired following a heart attack?
Reorganisation (replacement by fivrous tissue) - minimal regeneretive capacity for cardiomyocytes
Why is there a potential for cardiac rupture in the week following a AMI?
The structure of the heart is weakened
What are the symptoms of angina?
Pain, severe, crushing, sub-sternal, may radiate
With/without shortness of breath; lasts a few minutes
Females often present differently: nausea, vomiting, back/jaw pain
What causes angina?
Coronary artery disease, coronary vasospasm
i.e. imbalance: myocardial O2 demand >> O2 supply
When is urgent medical attention required for angina?
- worsening angina (unstable angina)
- chest pain lasting more than a few minutes
What are the three types of angina?
Chronic, stable
Unstable
Variant (vasospastic)
What causes chronic, stable angina?
In people with high levels of atherosclerosis, caused by ‘demand’, e.g. exercise, stress-test etc.
What causes unstable angina?
In people with some atherosclerosis, unpredictable, may involve thrombi formation
What causes variant angina?
In people without atherosclerosis, spasm of coronary artery
Which factors increase the risk and precipitate angina?
Risk factors: hypertension, cholesterol, smoking etc.
Precipitation factors: exertion, cold, stress, large meals etc.
How do you treat angina?
- Modification of risk factors: smoking, obesity, hypertension, hyperlipidemia, diabetes
- Surgical: angioplasty/stents/CABG Pharmacological: tPA (all immediate action)
- Drug treatments (chronic) (for relatively stable forms of angina)
What drugs are used to treat angina? What are their mechanisms?
- nitro-vasodilators
- β1 -adrenoceptor antagonists
- Ca2+ channel antagonists
Mechanisms
- Increased coronary perfusion to increase oxygen supply
- Decrased metabolic demand
- Combination of both
What is the role of nitric oxide (NO) in the cardiovascular system?
Antithrombotic
Vasodilator
What is the mechanism of nitrates in treating angina?
- Venous dilatation reduces venous pressure and pre-load, with consequent fall in cardiac oxygen consumption
- Arteriolar dilatation reduces peripheral resistance and after-load with consequent fall in cardiac oxygen consumption
- Coronary dilatation- e.g. variant angina
- No effect of NO in cardiac/sk muscle
In what forms can nitrates be administered for angina?
Fast-acting sublingual tablet prior to exertion
Chronic patch for stable angina
What are the limitations of using nitrates to treat angina?
- Decreased blood pressure is associated with a reflex tachycardia
- Tendency to increase cardiac oxygen consumption
Why must nitrate patches only be used for short periods of time?
To prevent tolerance
Where are majority of nitrates metabolised?
In the liver (>90%)
What are the adverse effects of nitrates?
- Hypotension (fainting): should not be combined with Viagra or similar drugs
- Tachycardia
- Headache
- Flushing
Right heart failure causes back pressure to which part of the circulation?
Systemic
Left heart failure causes back pressure to which part of the circulation?
Pulmonary
What can cause heart failure?
Hypertension
Heart conditions
- valves
- ischaemia
- arrythmia
- cardiomyopathy
- CHD, atherosclerosis
Lung conditions
- pulmonary hypertension
Other co-morbidities
- renal failure
- diabetes
What are the two types of chronic heart failure?
HFrEF: HF with reduced ejection fraction
HFpEF: HF with preserved ejection fraction
Which type of chronic heart failure involves systolic dysfunction?
HFrEF
Which type of chronic heart failure involves diastolic dysfunction?
HFpEF
In which populations is the prevalence of HFpEF particularly increasing?
Older population
Females
Diabetics
What are the features of HFpEF? What does the heart look like?
Preserved cardiac ouput (contraction)
Relaxation (diastole) impaied
Decreased cardiac output with exercise
Often caused by hypertension
What are the features of HFrEF? What does the heart look like?
Depressed cardiac output (ejection fraction)
Change in geometry (dilation)
Often caused by heart attacks that result in global remodelling
How does the cardiovascular system compensate for decreased cardiac output?
What does the compensatory mechanisms for decreased CO do to cardiac state over time?
Worsened cardiac state (positive feedback)
Define
ACE
a central component of the renin–angiotensin system (RAS), which controls blood pressure by regulating the volume of fluids in the body. It converts the hormone angiotensin I to the active vasoconstrictor angiotensin II
Define
ACE inhibitors
a class of medication used primarily for the treatment of high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease in blood volume, which leads to lower blood pressure and decreased oxygen demand from the heart
Define
ACE2
an enzyme attached to the cell membranes of cells in the lungs, arteries, heart, kidney, and intestines. It lowers blood pressure by catalysing the hydrolysis of angiotensin II into angiotensin
Define
Aldosterone
the main mineralocorticoid hormone, is a steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands and colon
Define
Aldosterone receptor antagonist
a diuretic drug which antagonizes the action of aldosterone at mineralocorticoid receptors. This group of drugs is often used as adjunctive therapy, in combination with other drugs, for the management of chronic heart failure
Define
Alpha receptor
any of a group of receptors that are present on cell surfaces of some effector organs and tissues innervated by the sympathetic nervous system and that mediate certain physiological responses (such as vasoconstriction, relaxation of intestinal muscle, and contraction of most smooth muscle) when bound by specific adrenergic agents
Define
Angiogram
the radiographic visualization of the blood vessels after injection of a radiopaque substance
Define
Angiotensin
a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. It also stimulates the release of aldosterone from the adrenal cortex to promote sodium retention by the kidneys
Define
Angiotensin I
formed by the action of renin on angiotensinogen and acts as the precursor to Ang II
Define
Angiotensin II
acts on the CNS to increase vasopressin production, and also acts on venous and arterial smooth muscle to cause vasoconstriction. It also increases aldosterone secretion; it therefore acts as an endocrine, autocrine/paracrine, and intracrine hormone
Define
Angiotensin receptor blockers
are a group of pharmaceuticals that bind to and inhibit the angiotensin II receptor type 1 (AT1) and thereby block the arteriolar contraction and sodium retention effects of renin–angiotensin system
Define
Angiotensinogen
an α-2-globulin synthesized in the liver and is a precursor for angiotensin, but has also been indicated as having many other roles not related to angiotensin peptides
Define
Arteriole tone
the degree of constriction experienced by a blood vessel relative to its maximally dilated state
Define
Beta blockers
any of a class of drugs (such as propranolol) that decrease the rate and force of heart contractions and lower high blood pressure by blocking the activity of beta-receptors
Define
Beta receptor
any of a group of receptors that are present on cell surfaces of some effector organs and tissues innervated by the sympathetic nervous system and that mediate certain physiological responses (such as vasodilation, relaxation of bronchial and uterine smooth muscle, and increased heart rate) when bound by specific adrenergic agents
Define
Bradykinin
a kinin that is formed locally in injured tissue, acts in vasodilation of small arterioles, is considered to play a part in inflammatory processes, and is composed of a chain of nine amino acid residues
Define
Calcium channel blockers
any of a class of drugs (such as verapamil) that prevent or slow the influx of calcium ions into smooth muscle cells and are used especially to treat some forms of angina pectoris and some cardiac arrhythmias
Define
Chronic obstructive pulmonary disease (COPD)
pulmonary disease (such as emphysema or chronic bronchitis) that is characterized by chronic typically irreversible airway obstruction resulting in a slowed rate of exhalation
Define
Diuretics
tending to increase the excretion of urine
Define
Echocardiogram
the use of ultrasound to examine the structure and functioning of the heart for abnormalities and disease
Define
Electrocardiogram
an instrument for recording the changes of electrical potential occurring during the heartbeat used especially in diagnosing abnormalities of heart action
Define
Hypertension
high blood pressure
Define
Inotropic agents
drugs that act by increasing or decreasing the force of muscular contractions
Define
Loop diuretic
a diuretic that inhibits reabsorption in the ascending limb of the loop of Henle causing greatly increased excretion of sodium chloride in the urine and to a lesser extent of potassium
Define
Polycythemia
a condition marked by an abnormal increase in the number of circulating red blood cells
Define
Pulmonary hypertension
a type of high blood pressure that affects the arteries in your lungs and the right side of your heart
Define
Pulmonary thromboendarterectomy
surgical excision of a thrombus and the adjacent arterial lining
Define
Renin
a proteolytic enzyme of the kidney that plays a major role in the release of angiotensin
Define
Thiazide diuretic
a type of diuretic (a drug that increases urine flow). They act directly on the kidneys and promote diuresis (urine flow) by inhibiting the sodium/chloride cotransporter located in the distal convoluted tubule of a nephron (the functional unit of a kidney).
Define
Type 1 pulmonary hypertension
the type of pulmonary hypertension that is associated with the narrowing of the small blood vessels in the lungs. It also is called pulmonary arterial hypertension (PAH) and includes cases where the underlying cause of the narrowing is not known (idiopathic pulmonary hypertension).
Define
Type 2 pulmonary hypertension
pulmonary hypertension caused by left heart disease. Long-term problems with the left side of the heart can lead to changes in the pulmonary arteries and cause pulmonary hypertension.
Define
Type 3 pulmonary hypertension
includes pulmonary hypertension resulting from lung diseases or shortage of oxygen in the body (hypoxia)
Define
Type 4 pulmonary hypertension
pulmonary hypertension caused by blood clots obstructing the pulmonary arteries. This also can be referred to as chronic thromboembolic pulmonary hypertension (CTEPH).
Define
Type 5 pulmonary hypertension
the type of pulmonary hypertension that includes other less-common causes that do not fit into any of the other four groups
Define
Vasoconstriction
narrowing of the lumen of blood vessels
Define
Vasodilation
widening of the lumen of blood vessels
Define
Vasopressin
a polypeptide hormone secreted by the posterior lobe of the pituitary gland or obtained synthetically that increases blood pressure and decreases urine flow
Definition
a central component of the renin–angiotensin system (RAS), which controls blood pressure by regulating the volume of fluids in the body. It converts the hormone angiotensin I to the active vasoconstrictor angiotensin II
ACE
Definition
a class of medication used primarily for the treatment of high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease in blood volume, which leads to lower blood pressure and decreased oxygen demand from the heart
ACE inhibitors
Definition
an enzyme attached to the cell membranes of cells in the lungs, arteries, heart, kidney, and intestines. It lowers blood pressure by catalysing the hydrolysis of angiotensin II into angiotensin
ACE2
Definition
the main mineralocorticoid hormone, is a steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands and colon
Aldosterone
Definition
a diuretic drug which antagonizes the action of aldosterone at mineralocorticoid receptors. This group of drugs is often used as adjunctive therapy, in combination with other drugs, for the management of chronic heart failure
Aldosterone receptor antagonist
Definition
any of a group of receptors that are present on cell surfaces of some effector organs and tissues innervated by the sympathetic nervous system and that mediate certain physiological responses (such as vasoconstriction, relaxation of intestinal muscle, and contraction of most smooth muscle) when bound by specific adrenergic agents
Alpha receptor
Definition
the radiographic visualization of the blood vessels after injection of a radiopaque substance
Angiogram
Definition
a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. It also stimulates the release of aldosterone from the adrenal cortex to promote sodium retention by the kidneys
Angiotensin
Definition
formed by the action of renin on angiotensinogen and acts as the precursor to Ang II
Angiotensin I
Definition
acts on the CNS to increase vasopressin production, and also acts on venous and arterial smooth muscle to cause vasoconstriction. It also increases aldosterone secretion; it therefore acts as an endocrine, autocrine/paracrine, and intracrine hormone
Angiotensin II
Definition
are a group of pharmaceuticals that bind to and inhibit the angiotensin II receptor type 1 (AT1) and thereby block the arteriolar contraction and sodium retention effects of renin–angiotensin system
Angiotensin receptor blockers
Definition
an α-2-globulin synthesized in the liver and is a precursor for angiotensin, but has also been indicated as having many other roles not related to angiotensin peptides
Angiotensinogen
Definition
the degree of constriction experienced by a blood vessel relative to its maximally dilated state
Arteriole tone
Definition
any of a class of drugs (such as propranolol) that decrease the rate and force of heart contractions and lower high blood pressure by blocking the activity of beta-receptors
Beta blockers
Definition
any of a group of receptors that are present on cell surfaces of some effector organs and tissues innervated by the sympathetic nervous system and that mediate certain physiological responses (such as vasodilation, relaxation of bronchial and uterine smooth muscle, and increased heart rate) when bound by specific adrenergic agents
Beta receptor
Definition
a kinin that is formed locally in injured tissue, acts in vasodilation of small arterioles, is considered to play a part in inflammatory processes, and is composed of a chain of nine amino acid residues
Bradykinin
Definition
any of a class of drugs (such as verapamil) that prevent or slow the influx of calcium ions into smooth muscle cells and are used especially to treat some forms of angina pectoris and some cardiac arrhythmias
Calcium channel blockers
Definition
pulmonary disease (such as emphysema or chronic bronchitis) that is characterized by chronic typically irreversible airway obstruction resulting in a slowed rate of exhalation
Chronic obstructive pulmonary disease (COPD)
Definition
tending to increase the excretion of urine
Diuretics
Definition
the use of ultrasound to examine the structure and functioning of the heart for abnormalities and disease
Echocardiogram
Definition
an instrument for recording the changes of electrical potential occurring during the heartbeat used especially in diagnosing abnormalities of heart action
Electrocardiogram
Definition
high blood pressure
Hypertension
Definition
drugs that act by increasing or decreasing the force of muscular contractions
Inotropic agents
Definition
a diuretic that inhibits reabsorption in the ascending limb of the loop of Henle causing greatly increased excretion of sodium chloride in the urine and to a lesser extent of potassium
Loop diuretic
Definition
a condition marked by an abnormal increase in the number of circulating red blood cells
Polycythemia
Definition
a type of high blood pressure that affects the arteries in your lungs and the right side of your heart
Pulmonary hypertension
Definition
surgical excision of a thrombus and the adjacent arterial lining
Pulmonary thromboendarterectomy
Definition
a proteolytic enzyme of the kidney that plays a major role in the release of angiotensin
Renin
Definition
a type of diuretic (a drug that increases urine flow). They act directly on the kidneys and promote diuresis (urine flow) by inhibiting the sodium/chloride cotransporter located in the distal convoluted tubule of a nephron (the functional unit of a kidney).
Thiazide diuretic
Definition
the type of pulmonary hypertension that is associated with the narrowing of the small blood vessels in the lungs. It also is called pulmonary arterial hypertension (PAH) and includes cases where the underlying cause of the narrowing is not known (idiopathic pulmonary hypertension).
Type 1 pulmonary hypertension
Definition
pulmonary hypertension caused by left heart disease. Long-term problems with the left side of the heart can lead to changes in the pulmonary arteries and cause pulmonary hypertension.
Type 2 pulmonary hypertension
Definition
includes pulmonary hypertension resulting from lung diseases or shortage of oxygen in the body (hypoxia)
Type 3 pulmonary hypertension
Definition
pulmonary hypertension caused by blood clots obstructing the pulmonary arteries. This also can be referred to as chronic thromboembolic pulmonary hypertension (CTEPH).
Type 4 pulmonary hypertension
Definition
the type of pulmonary hypertension that includes other less-common causes that do not fit into any of the other four groups
Type 5 pulmonary hypertension
Definition
narrowing of the lumen of blood vessels
Vasoconstriction
Definition
widening of the lumen of blood vessels
Vasodilation
Definition
a polypeptide hormone secreted by the posterior lobe of the pituitary gland or obtained synthetically that increases blood pressure and decreases urine flow
Vasopressin
What is the difference between primary and secondary hypertension?
Primary: Aetiology unknown, but risk factors include genetics, smoking, stress etc.
Secondary: High BP is a result of an abnormality/comorbidity or drug
What are the symptoms of hypertension?
Often no symptoms (silent killer)
What is hypertension a risk factor for?
Stroke
Heart failure
Coronary artery disease
What can cause secondary hypertension?
- Renal and renal vascular disease
- Coarctation (narrowing) of aorta
- Primary aldosteronism (Conn’s)
- Glucocorticoid excess (Cushing’s)
- Phaeochromocytoma (tumour releasing adrenaline/noradrenaline)
- Drugs (cocaine, ketamine, nicotine, tricyclic antidepressants, SSRIs, steroids, NSAIDS, EPO, angiogenesis inhibitors….etc)
Why is the pressure in the aorta and large arteries never below 70mmhg?
The aorta and large arteries are very elastic so pressure is maintained
What is the usual cause of high bp in younger and older individuals?
Young: High cardiac output (high heart rate)
Old: High total peripheral resistance
Most drugs that lower BP reduce what?
TPR
What is the cut-off for clinical high blood pressure?
140/90
What is the direct effects of long-term hypertension?
- causes target organ damage; exacerbates tissue inflammation, oxid stress, hormones (Ang II)
- blood vessels
- organs- e.g. heart; kidney, eyes etc.
What are the four classes of drugs used to treat hypertension? Which 3 are also used for heart failure?
ACE inhibitors & angiotensin antagonists
Beta blockers
Calcium channel blockers (NOT for HF)
Diuretics
How is HF treated?
- Lifestyle changes (weight, sodium, diet, exercise)
- Decrease cardiac workload
- Angiotensin inhibition
- Diuretics
- B blockers
- Increase cardiac contractility
- Positive inotropes (e.g. digoxin, dubutamine)
What are the peripheral effects of angiotensin II?
- vasoconstriction
- aldosterone release (sodium reabsorption-kidney)
- Increase NA release (sympathetic)
- Fibrosis
- Hypertrophy
- oxidative stress
What are the central effects of angiotensin II?
- Increase BP
- vasopressin release
- drinking response
What converts angiotensinogen into Ang I?
Renin
What causes renin to be released?
Renal sympathetic nerve activity
Renal perfusion pressure
Glomerular filtration
B-agonist
What natural molecule blocks the release of renin?
Atrial natriuretic peptide
What enzyme converts Ang I into Ang II?
ACE
Activation of AT1 (Ang II) receptors causes what?
Vasoconstriction
- Direct
- Via increased NA release from sympathetic nerves
Salt retention
- Aldosterone secretion
- Tubular Na+ reabsorption
Vascular growth
- Hyperplasia
- Hypertrophy
What is the suffix and some examples of ACE inhibitors?
-“pril”
captopril
enalapril
perindopril
What type of drug is captopril?
ACE inhibitor
What type of drug is enalapril?
ACE inhibitor
What type of drug is perindopril?
ACE inhibitor
What affects to ACE inhibitors have?
Prevent angiotensin II formation and inhibit bradykinin breakdown (Decrease Ang II, Increase BK)
- Decreases total peripheral resistance (vasodilator)
- Increases sodium & water excretion
What are the indications for ACE inhibitor use?
Hypertension, heart failure
Preserve renal function in diabetes (diabetic nephropathy)
What are the adverse effects of ACE inhibitors?
Common:
- cough (Increased BK in lungs), headache
- Marked hypotension (start with low dose)
- Hyperkalaemia (beware K+ supplements or K+ -sparing diuretics)
Infrequent:
- Rash/itch, angioedema
Contraindications:
- Renal failure if have bilateral renal artery stenosis
- Avoid in pregnancy
What two reactions does ACE facilitate?
Converting Ang I into Ang II
Breaking down bradykinin into inactive metabolites
What is the prefix and some examples of angiotensin receptor (AT1) blockers?
-“sartan”
Iosartan
Irbesartan
Candesartan
What effects for angiotensin receptor (AT1) blockers have?
inhibit angiotensin-induced vasoconstriction and aldosterone output (actually increase Ang II, unchanged BK- c.f. ACE inhibitors)
- Decreases total peripheral resistance (vasodilator)
- Increases sodium & water excretion
What are the indications for AT1 blocker use?
Hypertension, heart failure, diabetic nephropathy
For patients intolerant to ACE inhibitors (e.g. cough)
What are the adverse effects of AT1 blockers?
Same as ACE inhibitors:
Common:
cough (Increased BK in lungs), headache
Marked hypotension (start with low dose)
Hyperkalaemia (beware K+ supplements or K+ -sparing diuretics)
Infrequent:
Rash/itch, angioedema
Contraindications:
Renal failure if have bilateral renal artery stenosis
Avoid in pregnancy
What reaction does ACE2 facilitate?
Ang II into Ang(1-7)
What are the effects of Ang (1-7)?
Effects opposite Ang II (i.e. vasodilator, natriuretic)
Ang (1-7) may exert cardioprotective effects in its own right via another receptor; known as Mas receptor
True or False:
ACE2 is not blocked by ACE inhibitors
What receptor does SARS-Cov-2 bind to?
ACE2
What effects do B-adrenoceptor antagonists have?
- Decreased sympathetic drive to heart
- ↓ CO ↓ HR ↓ TPR
- Decrease sympathetic drive to kidneys
- Inhibit renin release (↓ Ang II)
What is the suffix and some examples of B blockers?
-“olol”
Propranolol (non-selective: B1 & B2)
Atenolol (B1 selective)
Metoprolol (B1 selective)
What are B blockers used to treat?
Hypertension (not first line)
Angina
Post myocardial infarct
Arrythmias
Clinically stable heart failure
Why are B blockers used in heart failure?
Chronic HF patients have massive sympathetic drive causing huge amounts of NA to be released. B-blockers reduce NA toxicity
What B-blockers are used in chronic stable HF?
Carvediol
Nebivolol
What are the long-term benefits and short-term risks of B-blockers in HF?
Long-term benefits:
- Improved survival
- Improved control of heart failure
- Reduced need for hospitalisation
- Improved quality of life
- Improved left ventricular ejection fraction
Short-term risks:
- Worsening heart failure
- Bradyarrythmias
- Prolonged intraventricular conduction
- Hypotension
- Worsening renal function
What are the adverse side-effects of B-blockers?
Respiratory: bronchoconstriction (B2 effect)
Cardiovascular: decreased heart contractility, bradycardia, atrioventricular block, exercise intolerance, claudication, impotence, beware sudden withdrawal
Diabetes: exacerbate & mask hypoglycemia
What are the effects of calcium antagonists?
Blockade of L-type (voltage operated) Ca2+ channels;
Reduces Ca2+ entry into vascular* / cardiac cells (not SkM)
Therefore, reduction in intracellular Ca2+
Fill in this table and explain the red arrows
Calcium antagonists with low cardiac effects cause an increase in HR in response to the drop in BP. Drugs with stronger cardiac effects prevent this through direct action on the heart
What are the indications for Ca channel blocker use?
Hypertension, angina, tachyarrhythmias (supraventricular)
What are the contraindication for Ca channel blocker use?
Heart failure
verapamil or diltiazem when combined with β-blocker
Why shouldn’t Ca channel blockers be used in patients with HF?
They reduce heart contraction
What are the adverse effects of Ca blockers?
cardiac depression, bradycardia (contraindicated in heart failure)
flushing, edema, dizziness, headache
constipation, nausea
What are the three classes of diuretic?
Loop diuretic
Thiazide diuretic
Aldosterone receptor antagonists
Which class of diuretic has the greatest efficacy?
Loop diuretic
What do loop diuretics do?
- Act at thick ascending limb of L of H to block Na+ /K+2Clsymporter
- Ceiling effect: block 15-25% filtered sodium reabsorption - class with greatest diuretic efficacy
What do Thiazide diuretics do?
- Act at distal conv tubules to block Na+ /Cl- symporter
- Modest increase in sodium excretion (5-10%)
When are loop diretics used?
Mild to moderate hypertension
When are Thiazide diuretics used?
oedema due to:
- congestive heart failure (+/- hypertension)
- +/- pulmonary congestion
- renal; liver disease
What are the adverse effects of loop/thazide diuretics?
- Electrolyte imbalance:
- Hypokalaemia (drug interactions)
- Hyperuricaemia (gout)
- hypercholesteraemia
- hyperglycaemia - diabetogenic effect
Which type of diuretic does not decrease K levels?
Aldosterone receptor antagonists
Where do aldosterone receptor antagonists act?
Distal tubule/collecting ducts
What actions does aldosterone receptor antagonists have?
- inhibits mineralocorticoid (aldosterone) receptor (kidney)
- Heart: inhibits aldosterone-induced fibrosis (improves HF)
What are the clinical uses of spironolactone (aldosterone receptor antagonist)?
- used in combination with thiazide or loop diuretics to produce (weak) diuresis without hypokalaemia
- used particularly in conditions associated with hyperaldosteronism
- resurgence of interest in CHF (improves survival)
- resistant hypertension? (add-on therapy)
What is a possible adverse effect of aldosterone receptor antagonists?
Hyperkalaemia
Why do aldosterone receptor antagonists lead to hyperkaelemia?
Aldosterone leads to production of Na/K channels that pump out K. If aldosterone is inhibited, these channels aren’t made and K is allowed to accumulate in the interstitium/blood
What is normal mean pulmonary pressure and what is considered pulmonary hypertension?
Normal: ~14/15mmHg
Hypertension: >25mmHg (at rest)
Why is the pulmonary arteries under significantly less pressure than other arteries?
The lungs are close to the heart so only need low pressure to get the blood there
Lung vessels are delicate
What are the symptoms of pulmonary hypertension?
- Shortness of breath
- difficulty breathing with exer:on,
- dizziness
- rapid breathing, and
- rapid heart rate
- Edema or swelling
- Chest pain
What are the risk factors for pulmonary hypertension?
Family history
Obesity combined with obstructive sleep apnea
Gender (women)
Pregnancy
Altitude
Other diseases (e.g. lupus)
Drugs and toxins (meth)
What is the cause of T1 pulmonary hypertension?
Idopathic
Inherited
Congenital heart disease
What is the cause of T2 pulmonary hypertension?
Diseases that affect the left side of the heart
What is the cause of T3 pulmonary hypertension?
Breathing conditions (e.g. COPD)
What is the cause of T4 pulmonary hypertension?
Blood disorders
How is pulmonary hypertension diagnosed?
ECG
Echocardiogram
Pulmonary function tests
Right heart catheterisation
Pulmonary angiogram
What pharcomalogical agents are used to treat pulmonary hypertension?
- Oxygen
- Anticoagulants
- Diuretics
- Inotropic agents
- Vasodilators
- Endothelin-1 antagonists
- Sildenafil (viagra)
How does oxygen treat pulmonary hypertension?
replaces the low oxygen in your blood.
How does anticoagulants treat pulmonary hypertension?
such as warfarin — decreases blood clot formation so blood flows more freely through blood vessels.
How does diuretics treat pulmonary hypertension?
” [such as furosemide, spironolactone] — removes extra fluid from the tissues and bloodstream, which reduces swelling and makes breathing easier.
How does inotropic agents treat pulmonary hypertension?
improves the heart’s pumping ability.
How do vasodilators treat pulmonary hypertension?
lowers pulmonary blood pressure and may improve the pumping ability of the right side of the heart.
How do endothelin-1 antagonists treat pulmonary hypertension?
helps block the action of endothelin, a substance that causes narrowing of lung blood vessels. These medications require monthly labwork to monitor liver function.
How do sildenafil treat pulmonary hypertension?
relaxes pulmonary smooth muscle cells, which leads to dilation of the pulmonary arteries.
What surgical therapies are used to treat pulmonary hypertension?
Pumonary thromboendarterectomy
Lung transplantation
How is T1 pulmonary hypertension treated?
Medications (pills, inhalers and continuous infusions) developed specifically for the treatment of PAH to dilate, and reduce the inappropriate growth of cells in, the pulmonary arteries
How is T2 pulmonary hypertension treated?
Therapies are focused on treating the underlying heart disease
How is T3 pulmonary hypertension treated?
Therapies focused on treating the underlying lung disease
How is T4 pulmonary hypertension treated?
Surgical removal of the clot, when possible, or oral medication if surgery is not possible or if PH remains after surgery
How is T5 pulmonary hypertension treated?
Therapies are focused on treating the underlying disease
Why does hypoxia cause constriction of the lung vessels?
The blood is diverted to the areas with good airflow by constricting the hypoxic vessels
What does endothelin-1 do in the lung vessels?
Vasoconstricter
decreases luminal radius
What happens to the smooth muscle surrounding lung vessels with chronic hypoxia?
Proliferation. SM layer thickens causing decreased luminal radius
What contributes to the increased vascular resistance caused by chronic hypoxia?
Hypoxic vasoconstriction
Vascular remodelling
Polycythemia
Activation of which pathway mediated Ca2+ sensitisation seen in pulmonary hypertension?
RhoA-Rho kinase (ROK) pathway
Plaque rupture may cause thrombus formation due all of the following EXCEPT:
a) release of tissue factor
b) activation of platelets
c) production of tissue plasminogen activator
d) production of fibrin
Plaque rupture may cause thrombus formation due all of the following EXCEPT:
a) release of tissue factor
b) activation of platelets
c) production of tissue plasminogen activator
d) production of fibrin
Used in the treatment of hypercholesterolaemia, statins act by:
a) increasing HMG-CoA reductase
b) decreasing endogenous cholesterol synthesis
c) reducing LDL plasma clearance
d) reducing plaque stabilisation
Used in the treatment of hypercholesterolaemia, statins act by:
a) increasing HMG-CoA reductase
b) decreasing endogenous cholesterol synthesis
c) reducing LDL plasma clearance
d) reducing plaque stabilisation
Acute coronary syndrome may be diagnosed if a patient exhibits any of the following signs EXCEPT:
a) persistent ECG changes
b) elevated blood pressure
c) chest pressure at rest
d) pain without ST-segment elevation on ECG
Acute coronary syndrome may be diagnosed if a patient exhibits any of the following signs EXCEPT:
a) persistent ECG changes
b) elevated blood pressure
c) chest pressure at rest
d) pain without ST-segment elevation on ECG
Hypertension and Heart failure may be managed with all of the following medications EXCEPT:
a) β1-adrenoceptor antagonists
b) AT1 receptor antagonists
c) calcium channel antagonists
d) loop diuretics
Hypertension and Heart failure may be managed with all of the following medications EXCEPT:
a) β1-adrenoceptor antagonists
b) AT1 receptor antagonists
c) calcium channel antagonists
d) loop diuretics
The following drugs are matched with a major adverse effect EXCEPT:
a) captopril and angioedema
b) frusemide and hyperkalaemia
c) spironolactone and hyperkalaemia
d) losartan and hyperkalaemia
The following drugs are matched with a major adverse effect EXCEPT:
a) captopril and angioedema
b) frusemide and hyperkalaemia
c) spironolactone and hyperkalaemia
d) losartan and hyperkalaemia
A 78-year-old female has been watching TV all afternoon by herself dozing in and out of sleep. Her daughter comes to visit and knocks on the door. The mother stands up to go and open the door and collapses. Her daughter uses a key to enter the house and finds her mother lying on the floor. The daughter calls 000 and the patient arrives at the hospital 1 hour later and has the following: slurred speech and right side hemiplegia. The first action should be to ………………. If it is an ischemic stroke in small cerebral artery, the second action should be to ………………
a) Perform a brain CT scan, administer tissue plasminogen activator
b) Perform a brain CT scan, give aspirin
c) Obtain a brain MRI, adminsiter mannitol
d) Obtain a brain MRI, remove the clot via mechanical thrombectomy
a) Perform a brain CT scan, administer tissue plasminogen activator
b) Perform a brain CT scan, give aspirin
c) Obtain a brain MRI, adminsiter mannitol
d) Obtain a brain MRI, remove the clot via mechanical thrombectomy
Which of the following are the MOST LIKELY mechanisms by which administration of stem cell treatment 7 days (delayed) post-stroke may improve outcome?
a) Immunomodulatory properties, stimulate angiogenesis, and repair mechanisms
b) Neuronal differentiation, stimulate angiogenesis, and immunomodulatory properties
c) Stimulate angiogenesis, repair mechanisms, and neuronal differentiation
d) Repair mechanisms, immunomodulatory properties, and neuronal differentiation
Which of the following are the MOST LIKELY mechanisms by which administration of stem cell treatment 7 days (delayed) post-stroke may improve outcome?
a) Immunomodulatory properties, stimulate angiogenesis, and repair mechanisms
b) Neuronal differentiation, stimulate angiogenesis, and immunomodulatory properties
c) Stimulate angiogenesis, repair mechanisms, and neuronal differentiation
d) Repair mechanisms, immunomodulatory properties, and neuronal differentiation
Which preclinical stroke model am I? I am the the most widely used model of stroke in rodents. I can accurately measure the level of cerebral ischaemia, but I do require invasive surgery. I am…?
a) Intraluminal suture middle cerebral artery occlusion model
b) Photothrombotic stroke model
c) Autologous blood injection model
d) Endothelin-1 middle cerebral artery occlusion
Which preclinical stroke model am I? I am the the most widely used model of stroke in rodents. I can accurately measure the level of cerebral ischaemia, but I do require invasive surgery. I am…?
a) Intraluminal suture middle cerebral artery occlusion model
b) Photothrombotic stroke model
c) Autologous blood injection model
d) Endothelin-1 middle cerebral artery occlusion
An 89-year-old patient was diagnosed with having a saccular aneurysm on his middle cerebral artery with minor/moderate symptoms. An MRI indicated that the aneurysm had ruptured. Which of the following approaches would MOST LIKELY be the best treatment option?
a) Surgical clipping
b) Endovascular coiling
c) Open surgery
d) Mannitol
An 89-year-old patient was diagnosed with having a saccular aneurysm on his middle cerebral artery with minor/moderate symptoms. An MRI indicated that the aneurysm had ruptured. Which of the following approaches would MOST LIKELY be the best treatment option?
a) Surgical clipping
b) Endovascular coiling
c) Open surgery
d) Mannitol
Richard is 65-years-old and has atherosclerosis, which is thought to have contributed to the development of an aortic aneurysm. What type of aortic aneurysm does Richard MOST LIKELY have?
a) Saccular
b) Fusiform
c) Dissecting
d) Giant saccular
Richard is 65-years-old and has atherosclerosis, which is thought to have contributed to the development of an aortic aneurysm. What type of aortic aneurysm does Richard MOST LIKELY have?
a) Saccular
b) Fusiform
c) Dissecting
d) Giant saccular
