The vascular system and stroke - Physiology Flashcards
a) What is the grey matter?
b) Describe the role of grey matter?
a) Closely packed neuronal cell bodies
b)
- Neuronal cell bodies are the metabolic centre of the nerve cell
- Neurone’s have large energy requirements
- They make their energy (ATP) through oxidative phosphorylation which requires oxygen and glucose
- It is the neurones that receive, process and output information
To ensure the blood supply the brain has some structural adaptations. Name two.
The circle of Willis
The microcirculation
a) What is the circle of Willis?
b) Describe the role of the circle Willis?
a) The circle of Willis is a ring of vessels that connects the anterior and posterior circulations of the brain. It is made up of four sources—the two internal carotid arteries and the two vertebral arteries
b) The circle of Willis provides a collateral blood flow between the anterior and posterior arterial systems of the brain and thus protects the oxygen supply from interruption by arterial blockage
Label the correct structures of the circle of Willis
Describe the role of the microcirculation
Has a high capillary density which optimises oxygen transport in the brain
What is the name of the physiological regulatory process that regulates and maintains cerebral blood flow (CBF)?
Autoregulation
What is cerebral autoregulation?
Cerebral autoregulation is a homeostatic process that regulates and maintains a relatively constant cerebral blood flow (CBF) despite changes in perfusion pressure
What mechanism does the brain use to regulate arterial pressure?
Negative feed back loop
The brain regulates arterial pressure though a negative feedback loop. Describe the negative feedback loop process
1) A decrease in arterial blood pressure is detected by baroreceptors
2) The medulla/hypothalamus then causes an increase in sympathetic outflow and a decrease in parasympathetic outflow
3) The increased sympathetic outflow causes vasoconstriction, increase in heart rate and an increase in force of cardiac contraction and increased peripheral vascular resistance
4) The decreased parasympathetic outflow causes an increase in heart rate leading to a higher cardiac output
Mean arterial pressure (MAP) plays a role in determining cerebral perfusion pressure (CPP). What is CPP?
CPP is the amount of pressure needed to maintain blood flow to the brain
CPP is related by two opposing factors. Name the two factors
Mean arterial pressure (MAP)
Intracranial pressure (ICP)
What is Mean arterial pressure (MAP)?
MAP is the driving force that pushes blood into the brain (controlled by brain)
What is Intracranial pressure (ICP)?
ICP is the force that keeps blood out of the brain
What is CPP a major determinate of?
Cerebral blood flow (CBF)
CPP is the major determinant of cerebral blood flow (CBF). Through autoregulation, the cerebral vasculature maintains a relatively constant CBF between a perfusion pressure range. What is this range?
50-150 mm Hg
What is the equation that links CPP, MAP and ICP
CPP = MAP - ICP
Why is it very important that MAP and ICP are tightly regulated
To maintain appropriate perfusion to the brain
Relating to the components of this equation CPP = MAP - ICP, what will a decrease in CPP (hence a reduced cerebral blood flow) result in?
Fall in MAP or rise in ICP
a) Name 3 factors that can increase ICP
b) What is the effect of an increased ICP?
a) Intracranial bleeding, cerebral oedema, tumour
b) Collapsed veins, decreases effective CPP, reduces blood flow
Explain what Cushing’s reflex is
- The Cushing reflex is a physiological nervous system response to acute elevations of intracranial pressure
- When ICP increases there is a decrease in cerebral perfusion to the brain
- This results in cerebral ischaemia
- The cerebral ischaemia (lack of oxygen) activates the sympathetic nervous system
- The sympathetic nervous system (SNS) activity increases systemic blood pressure in an effort to restore cerebral perfusion
- The increased blood pressure then signals the carotid and aortic baroreceptors to activate the parasympathetic nervous system, causing the heart rate to decrease.
As the pressure in the brain continues to rise, the brain stem may start to dysfunction, resulting in irregular respirations - The triad of a widened pulse pressure (increasing systolic, decreasing diastolic), bradycardia, and irregular respirations is known as Cushing’s triad
Name 2 specific mechanisms which mediate cerebral blood flow
- Blood brain barrier
- The neurovascular unit
Capillary structure in the brain is unique. What makes it unique?
Capillaries in the brain have astrocytic end feet sheaths
Describe the role of the blood brain barrier in in mediating cerebral blood flow
- Cerebral capillaries form a tight blood-brain barrier
- This tightly regulates the movement of ions, molecules, and cells between the blood and the brain.
Capillaries in the brain have astrocytic end feet sheaths. Describe the function of the astrocytes
Astrocytes interact with capillaries to:
- Regulate CBF
- Upregulate tight junction proteins
- Contribute to ion and water homeostasis
- Directly interface with neurones
Describe the role of the neurovascular unit in mediating cerebral blood flow
- The neurovascular unit is a component of the blood-brain barrier
- Neurons and cerebral blood vessels function as an integrated unit
- Both astrocytes and neurones cooperate in neurovascular coupling through glutamate signalling
- They produce an increase in local blood flow that is at least 4x greater than the increase in consumption of oxygen and ATP by the local neurons
Describe the myogenic control theory of autoregulation
- An increase in pressure cause the vascular smooth muscle cell membrane to be stretched
- This causes stretch sensitive ion channels to open
- This leads to calcium and sodium influx depolarisation and the opening of voltage gated calcium ion channels
- Rise in calcium ions causes muscle contraction (constriction)
- This restores blood flow
Describe the metabolic control theory of autoregulation
- If blood flow drops, the waste products of metabolism accumulate
- Some of these are vasodilatory metabolites that cause vasodilation and an increase in blood flow, restoring flow
- Vasodilatory metabolites include decreased PO2, pH, increased PCO2, rise in temperature, increases K+, increased lactate, increases osmolality, histamine and products of ATP breakdown (adenosine and inorganic phosphate)
a) What does Poiseuille’s law describe?
b) Describe how the values of Poiseuille’s law relate to each other
c) Poiseuille’s law is not used in clinical practice but is involved in some medical intervention. Provide 2 example of its use in clinical practise
a) The flow of liquid through a tube
b) Pressure difference in a tube (ΔP) relates to the viscosity of the fluid (μ), the length of the tube (L), the volumetric flow through the tube (Q) and the radio of the tube (r)
c) When resuscitating a patient who is haemodynamically unstable it is better to use a short wide cannula inserted into a large vein than a long thin one. E.g., Providing treatment to hypoglycaemic patients it is better to warm the glucose, making it less viscous and so therefore it is easier to inject
Describe the difference in resistance, blood flow and VSM contraction in small diameter and large diameter vessel
Describe the structure of smooth muscle myosin
- Made of 6 polypeptides
- 2 heavy actin heads and 2 tails
- Actin-binding site - binds to actin to allow contraction to take place
Describe the process of vascular smooth muscle (VSM) cell contraction and relaxation
- IP3 (a secondary messenger) binds to IP3 receptors in the sarcoplasmic reticulum and allows calcium to flood out
- The calcium then binds to calmodulin to form an active calcium aka calmodulin complex
- The calmodulin complex goes on to activate an enzyme called myosin light chain kinase (kinase are enzymes that phosphorylates proteins)
- The myosin light chain kinase phosphorylates the light chain (LC20) of myosin, which activates the myosin to contract
- Myosin phosphatase dephosphorylates the myosin light chain, which means the myosin can’t integrate with actin. The myosin goes into an inactive state and and the VSM relaxes
For a cell to relax the calcium levels need to be lowered. Describe how calcium level go down
- By pumping calcium back into the sarcoplasmic reticulum
- Extracting it from the cells and outside by Ca-Mg ATPases and Na-Ca exchangers
Describe the role of c-AMP and c-GMP (secondary messengers) on vascular smooth muscle cells
c-AMP inhibits myosin light chain kinase and stop the phosphorylation of myosin and so makes VSM cells relax
c-GMP stimulates myosin light chain phosphatase which promotes desphosporylation of the myosin light chains and makes the VSM cells relax
Describe the role of endothelin in vasoconstrictors
- Endothelin is produced as a pro-hormone big endothelins
- It is converted to endothelin by endothelin converting enzyme
- The endothelin diffuses from endothelium cells to vascular smooth muscle cells where it can bind to ETA receptors and excite contraction of the vascular smooth muscles (vasoconstriction)
- Endothelin can also act on ETB receptors which are found on the endothelial cells and up regulate nitric oxide synthase. This causes relaxation of vascular smooth muscle (vasodilation)
Prostaglandins have a role in vasodilation and vasoconstriction. Name 2 prostaglandin vasodilators and vasoconstrictors
Vasodilator - PGE2, PGI2
Vasoconstrictor - PGD2, PGF2
Describe the role of bradykinin and lysylbradykinin on vascular smooth muscle cells
- Acts by stimulating the release of NO which binds to B2 receptors in endothelial cells
- This causes vasodilation
a) Describe the role of noradrenaline of the sympathetic nervous system in the regulation of blood flow (vascular smooth muscle cell)
b) Describe the role of Adrenaline of the sympathetic nervous system in the regulation of blood flow (vascular smooth muscle cell)
- Noradrenaline/norepinephrine binds to alpha 1-adergenic receptor which activates phosphate lipase C
- Phosphate lipase C activates IP3
- IP3 binds to the endoplasmic reticulum, releasing intracellular calcium ions
- This causes contraction of the vascular smooth muscle cells (vasoconstriction)
Describe the role of acetylcholine of the parasympathetic nervous system in the regulation of blood flow (on the vascular smooth muscle cells)
Acetylcholine can bind to acetylcholine receptors (MR) in the endothelial cells and up-regulate NOS and cause vascular smooth muscle relaxation (vasodilation)
Describe the role of the renin and angiotensinogen system on the vascular smooth muscle cells
- Low blood pressure causes kidney to release renin
- Renin converts angiotensinogen (produced by the liver) to angiotensin I
- Angiotensin I is converted by ACE (a type of enzyme found in the lungs) to angiotensin II
- Angiotensin II causes vasoconstriction (and decreases GFR and decreases urine output. Also acts on adrenal gland to produce aldosterone which increases sodium and water retention)
