What are the population data for cardiovascular disease?
• Total global deaths – 16.7 million
– Coronary heart disease – 7.2 m
– Stroke – 5.5 m
– Hypertensive heart disease – 0.9 m
– Inflammatory heart disease – 0.4 m
– Rheumatic heart disease – 0.3 m
– Other multi causal (incl. peripheral vascular disease) – 0.9 m
• Directly attributable to high blood pressure
– 49% for coronary heart disease – 62% for stroke
-hypertension is high blood pressure
What is the disease burden of cardiovascular disease?
-% of disability adjusted life years -the highest! -males 15 y. o. and above
What is the relationship between systolic blood pressure and CV disease (cardiovascular)?
-The risk of CV disease increases with every increase in systolic blood pressure
What is the definition of high blood pressure?
-Currently the definition of high blood pressure is >140/>90 (systolic/diastolic)
Blood pressure increases with age except when:
- NaCl intake is low - Physical activity is high -Obesity is absent
How many people have high blood pressure?
- In most countries (developing and developed) - 30% of adults have high blood pressure - 50‐60% more would have better health is BP were lowered.
How can you prevent the increase in high blood pressure?
-Increased physical activity -Maintenance of ideal body weight -Better diet (fruit and vegetable intake)
Are most organs in the body innervated by the autonomic nervous system?
-most organs of the body receive a level of innervation from the autonomic nervous system -from your pupils to your reproduction -most functions of the body comes from the autonomic nervous system
What is the two neuron chain involved in the autonomic control (sympathetic)?
-the neurons that control the sympathetic activity to the organs are part of a two neuron chain, preganglionic neurons exist in the spinal cord, have a short projection to the sympathetic chain where synapse to the post ganglionic neurons that then go to the target tissue
What effect does sympathetic innervation have on blood vessels?
-projection of the sympathetic neuron onto the blood vessel causes constrictions -so increase in neural stimulation causes constriction -increase in peripheral resistance -that is how it can change blood pressure
What effect does the sympathetic innervation have on the pacemaker cells of the heart?
-increases heart rate (tachycardia)
What is the sympathetic nervous system like for controlling the blood pressure?
-sit at a midrange -can increase and decrease vascular tone and heart rate
How does the parasympathetic nervous system affect the pacemaker cells of the heart?
-parasympathetic also projects to the pacemaker cells -this decreases the heart rate
What are the characteristics of a somatic nervous system neuron?
-cholinergic neuron, innervating skeletal muscle -projects from the CNS to the muscle, it releases acetylcholine there onto N1 nicotinic acetylcholine receptor to cause contraction
What are the characteristics of an autonomic nervous system neuron? (pre ganglionic)
-also cholinergic -both sympathetic and parasympathetics preganglionic neurons use acetylcholine on N2 nicotinic acetylcholine receptor
What are the characteristics of the postganglionic neurons in the parasympathetic nervous system?
-the postganglionic in parasympathetic use acetylcholine onto M (muscarinic acetylcholine receptor), metabotropic receptors! -they are short, usually in the tissue they are innervating
What are the characteristics of the postganglionic neurons in the sympathetic nervous system?
-the postganglionic in sympathetic use noradrenaline (onto alpha and beta adrenoergicg receptors)
What is the special case of the sympathetic nervous system?
-special components: adrenal medulla, rather than postganglionic neuron have chromaffin cells that release adrenalin into the environment
Where are the sympathetic preganglionic neurons located?
-in the spinal cord
-thoracic and upper lumbar part
-in the butterfly (have the gray matter)
-in the lateral horn, called the intermediolateral cell column (IML)
-these are motor neurons so they project through the ventral horn
What is the anatomy of the pre and postganglionic neurons and the sympathetic chain?
-go through the visceral efferent fibre
-then project through the white communicating ramus (white= myelinated)
-pre-ganglionic neurons are myelinated, white and use ACh so fast fast fast
-then synapse onto postganglionic neurons that project via gray communicating ramus (unmyelinated), slow conducting
-the beads are the ganglia (collections of postganglionic neuron cell bodies)
-called the sympathetic chain (the beads)
What is the prevertebral chain?
-another group of ganglia, along the midline, viscera -provide mainly the intestines, -prevertebral and paravertebral
What is the connection of the sympathetic postganglion neuron and the target tissue?
-postganglionic neuron projects to the target, the sympathetic ones have long projections to the target tissue (unlike parasympathetic) -doesn't have a direct connection (synaptic) -has multiple vesicle release sites -throughout long distances of the axon, each can be the release site and can affect several muscles -diffuse network of terminals
How can the sympathetic nervous system control blood flow?
-level of constriction and tone of blood vessels at any time
-can increase the activity get constriction or dilation
Does the output have tonic output?
What is this?
-second from the bottom: 2nd thoracic segment, pre-ganglionic sympathetic neuron
-the 3rd from the bottom is blood pressure
-measuring temperature of the spinal cord (the most bottom one)
-axon signals are temperature dependent (the channels), if too cold you stop the creation and conduction of APs
-if temperature goes down the neuron slows down activity and then stops
What is this?
-upper line, normal person -below, person with a lesion below thoracic and lumbar -when have lesion, you lose the sympathetic and parasympatehtic activity!
Is there ongoing activity in sympathetic nerves supplying the musculature?
-yes -this is dependent on drive from the centers above the spinal cord -some sort of drive above, to maintain the blood pressure -excitatory input that maintains the tonic
How can a person with a high level spinal lesion survive?
-because blood pressure is pulled up by the hormones not the neurons (from kidney, angiotensin) -the regulation by the hormones is less specific, not as fine tuned
Describe the first part of this:
-have the preganglionic neurons in the spinal cord and they have effect on the primary motor neurons that then target the muscle
-know that something needs to be controlling them
What is this?
-recording of a blood pressure through finger
-exercise at different levels
-with increase in activity, increase in systolic blood pressure (less in diastolic) and increase in heart rate
How does the body know to increase the blood pressure and sympathetic activity in response to exercise?
-can thinking about exercise have an effect on blood pressure -general paralysis, thinking about exercise and see if that increases blood pressure (think of constricting the muscle) -blood pressure increases! just thinking about constricting muscle does something to the autonomic system -central command is an aspect of increasing the blood pressure
How does exercising a muscle affect the blood pressure? (sensory aspect)
-stimulate muscle, the activity drives the increase in blood pressure too -so afferent feedback also has effect -sensory input feeds in -the process of exercising a muscle increases sympathetic activity to the cardiovascular system
What are some of the inputs coming into the control of blood pressure?
-sensory feedback and central command go together -something up in the brain is also inhibitory, since when the forebrain is removed bigger response
What happens when no cerebral cortex is there and stimulate the muscle?
-with no cerebral cortex -when stimulate muscle, get even bigger response, this tells us that there is another level of complexity
What is the exercise pressor reflex?
-have local reflex loops that affect the response to exercise -the exercise pressor reflex also involves an excitatory spinal circuit that acts in the absence of higher brain inputs -(reflex loops in the blood pressure circuitry) -hierarchical control, from single spinal cord control
How do they figure out the connections in the circuits?
-they need excitatory drive to act (they use pseudoviruses, rabies, that get through the axons into the brain and see where they end up and gives you an idea about what neurons are there -get an idea about where the drive comes from -neurotropic virus (pseudorabies) -herpes simplex virus as well -who has the ability to control whom
What are some of the main players in the control circuit?
-PVN (paraventricular nucleus) -lateral hypothalamic area (LHA) -A5 (cells catecholnergic in the pons) -rostral ventral lateral medulla -rostral ventral medial medulla -raphe (seronnin) -hypothalamus, pons and medulla (the main players!!!
What is a reflex loop?
-have a loop, from the sensory neuron, sensory afferent and drives the postganglionic sympathetic neuron
How do you know which part of hierarchy is important?
-rostral ventro lateral medulla (RVLM) -if inject glycine here the sympatehtic activity falls and the blood pressure falls -if kill those neurons the sympathetic activity disappears -if then cut the spinal cord, no further change =this is showing that the RVLM is the key region -use glutamate, regulate most of the sympathetic input out of the brain
• Cardiovascular diseases represent the greatest cause of morbidity and mortality in both the developed and developing worlds. • Hypertension is a major risk factor for the development of cardiovascular diseases. • Whilst regulation of the cardiovascular system is multi‐factorial and complex, the sympathetic nervous system exerts influence at multiple levels, including development of the vasculature and regulation of vascular tone, cardiac function and blood volume. • Sympathetic activity to the vasculature is tonic – it can be increased and decreased to regulate total peripheral resistance. • Control of sympathetic outflow has a hierarchical organization. • Excitatory drive from higher brain regions is essential for tonic activity. • Sensory input directly modulates the activity of sympathetic pre-ganglionic neurons to alter blood pressure during exercise, pain, thermoregulation etc. • Higher brain centers contribute both excitatory and inhibitory modulation of this reflex activity.