5. Autonomic Nervous System/ Controlling BP Flashcards
7 parts of the nervous system
• CNS • Peripheral nervous system ○ Soamtic (voluntary) ○ Autonomic nervous (involuntary) ▪ Sympathetic ▪ Parasympathetic ▪ enteric
Somatic nerve fibres
• Sensory neurons – info from neurons to nervous system
• Motor neurons – info from nervous system to neurons
○ One motor neuron innervates one effector
Autonomic nervous system - controls
Responsible for control of the bodily functions that are not consciously directed Controls - heart rate - body temp - blood pressure - force of heart contraction
Autonomic nervous system - innervates
Involuntary smooth muscle
Cardiac muscle
Glands
2 branches of the autonomic nervous system
Sympathetic - fight or flight
Parasympathetic - rest and digest
Innervate same organs but have opposite effects
Sympathetic nerve fibres
- Short preganglionic fibres myelinated – release norepinephrine
- Long postganglionic fibres unmyelinated – release acetylcholine
- Cholinergic pre ganglionic fibres
- Adrenergic post ganglionic fibres
Parasympathetic nerve fibres
- Long preganglionic fibres myelinated – release acetylcholine
- Short postganglionic fibres unmyelinated – release acetylcholine
- Ganglia is near or in effector organs
- Cholinergic pre and post ganglionic fibres
Location of sympathetic nerves
- originate in Thoracolumbar outflow - T1-L2
Location of parasympathetic nerves
- some originate from cranial region some from sacral region Craniosacral outflow - CN III, VII, IX, X, S2-S4
• Cranial region – nerve 3 oculomotor nerve, 7, 9 glossopharyngeal nerve, 10 vagus nerve
Ganglia
• Collection of neuronal bodies or group of nerve cell bodies in peripheral nervous system = groups of cells in the nervous system
Parasympathetic gangla
has terminal or intramural ganglion (very close to effector organ)
2 types of sympathetic ganglia
– Paravertebral/chain ganglia
– Prevertebral/pre-aortic/collateral/subdiaphragmatic ganglia
– Paravertebral/chain ganglia
- found on either side of the vertebrae
- Arranged in chains (hence name chain ganglia)
- 24 of these ganglia
- Name according to region
– Prevertebral/pre-aortic/collateral/subdiaphragmatic ganglia
• In front of the vertebral (named based on location)
Path of preganglionic fibres
- white rami communicants (looks white due to preganglionic fibre myelination)
• Intermediate lateral grey horn –> Ventral root –> ventral rami –> synapse in chain ganglia –> post ganglionic fibres arise
4 ways that preganglionic fibres synapse
• Can also synapse at chain ganglia at lower levels
• Can also synapse at chain ganglia at higher levels
• Could also synapse at prevertebral ganglia instead of chain ganglia = post ganglionic fibres give rise to splanchnic nerve (any nerve that goes out by itself supply abdominal and visceral area)
• Could synapse at chain ganglia at higher levels but post ganglionic fibres goes out of another root by itself (not following grey rami communicants)
○ forming cardiopulmonary nerve (splanchnic nerve coming from cervical and upper thoracic ganglia – supplies heart, nerve and organs in thorax)
Splanchnic nerve
(any nerve that goes out by itself supply abdominal and visceral area)
- occur when preganglionic fibres synapse at prevertebral ganglia instead of chain ganglia
cardiopulmonary nerve
(splanchnic nerve coming from cervical and upper thoracic ganglia – supplies heart, nerve and organs in thorax)
Path of post ganglionic fibres
– grey rami communicants
• Through ventral rami –> go out
3 main postganglionic fibres of sympathetic system (flight or fight response)
- Pilomotor fibres – supply arrector pili
- Vasomotor fibres – blood vessels
- Sudomotor fibres – sweat glands
Receptors of sympathetic nervous system
- Release norepinephrine
- Pupils – alpha 1 receptor – cause dilation
- Airway – beta 2 – relaxtion
- Heart – beta 1 – increased hr
- Sweat glands – alpha 1 and m3 – localised and general secretion
Receptors of parasympathetic nervous system
- Release acetlycholine
- Pupil – M3 receptor – constriction
- Airway – M3 – contraction
- Heart – M2 – decreased hr
ANS controls
- Heart rate
- Force of contraction of the heart
- Peripheral resistance of the blood vessels
What does the ans not do
• The ANS does not - Initiate electrical activity in the heart
But can increase or decrease heart rate
Parasympathetic nervous system - innervates what parts of the hearts
- SA node
- AV node
- N.B little/none to ventricles – don’t supply ventricles or contractile muscles
Sympathetic nervous system - innervates what parts of the hearts
Ventricles
- Atria
- SA and AV node
Steps- sympathetic nervous system and increase heart rate
- Sympathetic innervation to nodal cells
• Sympathetic nervous system→ Norepinephrine •- norepinephrine binds to beta 1 adrenergic receptorr –> Stimulate β1 adrenergic receptors
• Activate G stimulatory proteins, release GDP binds GTP - Activates adenylate cyclase (A.C)
• A.C converts ATP→ cAMP→ Protein kinase A (PKA) - PKA phosphorylates L-type Ca 2+ channels = actiavte it
• More Ca2+ within cell→ depolarise quicker→ Increase frequency of action potentials→ - Increased heart rate
- norepinephrine binds to beta 1 adrenergic receptorr –> Stimulate β1 adrenergic receptors
Norepinephrine binds to
- norepinephrine binds to beta 1 adrenergic receptorr –> Stimulate β1 adrenergic receptors
Action of G stimulatory protein when activated
• Activate G stimulatory proteins, release GDP binds GTP
Activates adenylate cyclase (A.C)
• A.C converts ATP→ cAMP→ Protein kinase A (PKA)
Steps- sympathetic nervous system and contractility
- Sympathetic innervation
• Sympathetic nervous system→ Norepinephrine- norepinephrine binds to beta 1 adrenergic receptorr –> Stimulate β1 adrenergic receptors
• Activate G stimulatory proteins, release GDP binds GTP - Activates adenylate cyclase (A.C)
• A.C converts ATP→ cAMP→ Protein kinase A (PKA) - PKA phosphorylates L-type Ca 2+ channels = actiavte it
• More Ca2+ within cell - PKA phosphorylates channels in sarcoplasmic reticulum→ more Ca2+ moves into sarcoplasmic reticulum
- → Ca2+ flowing into sarcoplasmic reticulum, means pumps become more active induced Ca2+ release (more calcium pumped out) increases significantly
- More calcium helps to form more actin and myosin cross bridges → Increased contraction
- norepinephrine binds to beta 1 adrenergic receptorr –> Stimulate β1 adrenergic receptors
Steps -Parasympathetic nervous system and heart rate
Decreased
- Parasympathetic nervous system→ Acetylcholine
- Acetylcholine binds and Stimulate Muscuranic type 2 (M2) receptors
• Activate G inhibitory proteins (has alpha, beta and gamma)
• Alpha separates from beta and gamma - Beta and gamma binds to and open K+ channels→ K+ moves out→ hyperpolarise the cells
- Decrease frequency of action potentials→ Decrease heart rate
- Alpha subunit inhibits A.C→ cAMP levels drop→ low Ca2+ entry, decrease pKa less calcium in and more potassium lost
- Acetylcholine binds and Stimulate Muscuranic type 2 (M2) receptors
Acetylcholine binds to
- Acetylcholine binds and Stimulate Muscuranic type 2 (M2) receptors
Action of G inhibitory protein when activated
- Activate G inhibitory proteins (has alpha, beta and gamma)
- Alpha separates from beta and gamma
- Beta and gamma binds to and open K+ channels→ K+ moves out→ hyperpolarise the cells
- Alpha subunit inhibits A.C→ cAMP levels drop→ low Ca2+ entry, decrease pKa less calcium in and more potassium lost
Paraysmpathetic and sympathetic impacting SA nodal action potentials
Phase 4 is changed by sympathetic and parasympatheitc activity
• Sympathetic = phase 4 happens faster slope is increased
• Parasympathteic = phase 4 is slower, slope is decreased
Vasculature and innervation
- most vessels receive sympathetic innervation
* Exceptions − some specialised tissue e.g. erectile tissue have parasympathetic innervation
Vasculature and receptors
- most arteries and veins have α1-adrenoreceptors (binding site for norepinephrine/ noradrenaline)
- coronary and skeletal muscle vasculature also have β2-receptors
Vasomotor tone
Need to have a resting/ baseline level of tone of vasculature
• Tension exerted by vascular smooth muscle is called vasomotor tone
Vasodilation
Decrease noradrenaline on the receptors
Vasoconstriction
Increasing noradrenaline on the receptors
Vessels that have β2-adrenoreceptors as well as alpha 1
– Skeletal muscle
– Myocardium
– Liver
What happens in Vessels that have β2-adrenoreceptors as well as alpha 1
At normal adrenaline levels
• Circulating adrenaline has a higher affinity for β2 adrenoceptors than for α1 receptors
• Alpha 1 receptor activation by noradrenaline
• At physiological concentration circulating adrenaline will preferentially bind to β2 adrenoceptor
Causing vasodilation
What happens in Vessels that have β2-adrenoreceptors as well as alpha 1
At higher adrenaline levels
At higher or abnormal (supraphysiological adrenaline conc) concentrations it will also activate α1 receptors as well as beta 2
• causing Overriding vasoconstriction of the vessels
•Activating β2 adrenoreceptors causes
Vasodilation
•Activating α1 adrenoreceptors causes
Vasoconstriction
How do β2 adrenoreceptors cause vasodilation
• Beta 2 adrenarecptors are linked to stimulatory g proteins
– increases cAMP → PKA (protein kinase a)→ opens potassium channels + inhibits MLCK (myosin light chain kinase)→ relaxation of smooth muscle = vasodilation
How do α1 adrenoreceptors cause vasoconstriction
• Activate Gq units
• Produce IP3
• Stimulates calcium ion release from sarcoplasmic reticulum
• Calcium binds to calmodulin (CAM)
• Acts on myosin light chain kinase MLCK
• Gq protein facilitates mobilisation of DAG – diacylglycerol
• DAG activates protein kinase c PKC
• PKC inhibits MLCP – myosin light chain phosphatase
• Inhibits dephosphorylation of myosin light chain
= vasoconstrictions
Local metabolites and vasodilation
- Local increases in metabolites have a strong vasodilator effect
- Increase flow to exercising skeletal muscles
- Metabolites are more important for ensuring adequate perfusion of skeletal and coronary muscle than activation of β2-receptors
Local metabolites examples
• Active tissue produces more metabolites (metabolites increase rapidly in exercise)
– e.g. adenosine, K+, H+, increase PCO2 (disolved co2)
Baroreceptors
– Baroreceptors (high pressure side of system)
Atrial receptors
– Atrial receptors (low pressure side of system)
Overall flow of CVS
• Changes in the state of the system are communicated to the brain via afferent nerves
Neurons control amount of parasympathetic and sympathetic outflow from medulla oblongata
- Alters activity of efferent nerves
- Efferent inputs controls arteriole blood pressure
Baroreceptor reflex
What is it
- The baroreceptor reflex is important for maintaining blood pressure over short term
- It compensates for moment to moment changes in arterial BP
- HOWEVER…. Baroreceptors can re-set to higher levels with persistent increases in blood pressure
Normal blood pressure
• Normal: 120/80 mmHg
Hypotension
• Hypotension: 90/60 mmHg
Hypertension
• Hypertension: 140/90 mmHg
Arch of aorta structures
- Brachiocephalic trunk – right common carotid (split into internal and external) and right subclavian artery
- Left common carotid – internal and external
- Right subclavian artery
Location of baroreceptors
• Arterial baroreceptors are located in the carotid sinus (at the bifurcation of external and internal carotids of the right and left common carotid branches) and in the aortic arch
Function of arterial baroreceptors
• Detect change in pressure as soon as blood leaves the heart
- If arterial pressure suddenly rises, the walls of these vessels passively expand, which increases the firing frequency of action potentials generated by the receptors
- If arterial blood pressure suddenly falls, decreased stretch of the arterial walls leads to a decrease in receptor firing.
How is hypotension detected
• Baroreceptors in carotid and aortic sinus sense the low blood pressure
- Aortic sinus has sensory afferent fibers of CN X (cranial nerve 10 = vagus)
- Carotid sinus has sensory afferent fibers of CN IX (cranial nerve 9)
- Information from CV X and CN IX→ Nucleus of tractus solitarius in medulla (group of cells in medulla)
- Detects issue
• Aortic sinus has sensory afferent fibers
• Aortic sinus has sensory afferent fibers of CN X (cranial nerve 10 = vagus)
• Carotid sinus has sensory afferent fibers of
• Carotid sinus has sensory afferent fibers of CN IX (cranial nerve 9)
Blood pressure increasemechanism
BP= CO x TPR – blood pressure equation
What are compensation mechanisms
- When BP is low, compensation mechanisms aim act to increase CO by increasing neart rate and stroke volume
- Nucleus of tractus solitarius in medulla→ stimulate cardiac acceleratory centre and vasomotor centre and inhibit the cardiac inhibitory centre
Cardiac acceleratory centre
= Cardiac acceleratory centre→ Fibers come down→ T1-T5→ sympathetic chain ganglion→ innervate SA node and AV node
4 Short term compensation mehcanisms – hypotension
Methods sympathetic nervous system uses to increase blood pressure
* SNS influence adrenal medulla * SNS increase vasoconstriction * SNS increase contraction * SNS increase heart rate
Hypotension – SNS increase heart rate
Cardiac acceleratory centre → innervate SA node and AV node
In the SA and AV node these nerve fibes: = • Sympathetic fibers → Norepinephrine → binds to β1 adrenoceptors (G stimulatory GDP-->GTP) → activate adenyly cyclase → activate protein kinase A → phosphorylate (activate) Ca2+ channels → more Ca2+ coming in → more frequent action potential (as cell is depolarizing fast) → Increase heart rate → Increase CO → Increase BP
Hypotension – SNS increase contraction
Cardiac acceleratory centre → innervate contractile cardiomyocytes
• Sympathetic fibers
→ Norepinephrine
→ binds to β1 adrenoceptors (G stimulatory GDP–>GTP)
→ activate adenyly cyclase
→ activate protein kinase A
→ phosphorylate (activate) Ca2+ channels
→ more Ca2+ coming in
→ ca2+ binds to TnC on troponin – more myosin actin cross bridges
→ Increase contraction
→ Increase stroke volume
→ Increase BP
Hypotension: SNS increase vasoconstriction
Cardiac acceleratory centre → innervate contractile cardiomyocytes
Sympathetic fibers go into smooth muscle cells in tunica media → Tunica media of blood vessels → Norepinephrine → binds to α1 adrenoceptors → more Ca2+ coming in → vasoconstriction → decrease radius of blood vessels → Increase total peripheral resistance (8nl/pie r4) → Increase BP
Hypotension: SNS influence adrenal medulla
Cardiac acceleratory centre → Fibers come down→ T1-L2 → sympathetic chain ganglion → synapse directly in adrenal medulla
• Chromaffin cells in adrenal medulla
→ release Epinephrine (80%) and norepinephrine (20%)
• Epinephrine and norepinephrine acts to increase heart rate (SA node/AV node),
increase contractility (contractile cardiomyocytes)
increase total peripheral resistance (vasoconstriction)
RAAS Hypotension – long term compensation
And the kidneys
(Production of angiotensin 2)
- At glomerulalr apparatus = Low BP detected by juxtaglomerular (JG) cells in kidneys
- The Epinephrine released activate JG cells by binding to β1 adrenoceptors
- In response, JG cells release renin into circulation
- • Liver produces angiotensinogen (inactive protein)
• Renin cleaves angiotensinogen and converts it to angiotensin I (Ang I) - Ang I via circulation reach pulmonary capillaries in lung
- Lungs produce an enzyme called angiotensin converting enzyme (ACE)
• ACE converts Angiotensin I to Angiotensin II (Ang II)
Angiotensin II
Functions
- Ang II stimulate zona glomerulosa cells to release Aldosterone (increase Na+ reabsorption)
- Ang II stimulates supraoptic nucleus of hypothalamus to release ADH (increase water reabsorption)
- Ang II stimulated hypothalamic thirst centres
- Ang II can cause vasocontriction
Adh
- ADH acts in collecting duct of nephron→ increase water reabsorption
- ADH binds to V2 receptors in collecting duct→ G stimulatory protein→ produce aquaporins (Type II)→ increase water reabsorption
• Increased water reabsorption→ Increased blood volume→ Increased EDV→ Increased SV→ Increased CO→ Increased BP
Aldosterone
• Aldosterone acts on distal convoluted tubule→ increased reabsorption of Na+→ Increased reabsorption of water
Oliguria
• Oliguria (reduced urine output) seen in patients with hypotension
Hypertension - effects
Profound effect on kidney, heart and brain as it damages endothelium and blood vessels
2 parts of vasomotor centre
• The vasomotor centre has two parts→ C1 (for vasoconstriction) and A1 (for vasodilation)
How do compensation mechanisms in hypertension work
Nucleus of tractus solitarius in medulla→ stimulate cardio inhibitory centre and vasomotor centre (A1 area) and inhibit the cardio acceleratory centre
Hypertension - inhibition of cardio acceleratory centre
Decreased heart rate due to reduced stimulation of SA node and AV node→ Decreased HR→
Decreased CO→ Decreased BP
• Reduced contraction of smooth muscles of blood vessels→ leads to vasodilation→ Decreased TPR→
Decreased CO→ Decreased BP
• Reduced stimulation of adrenal medulla→Reduced Epinephrine→leads to vasodilation→Decreased BP
Hypertension - activation of cardio inhibitory centre i
Cardio inhibitory centre→ has parasympathetic fibers (Dorsal nucleus of vagus)→ innervate SA node
(right vagus) and AV node (left vagus)
• No parasympathetic innervation to myocardium!
• Parasympathetic fibers→Acetylcholine→binds to muscuranic type 2 receptors→G inhibitory proteins (alpha subunit) → CAMP levels decrease→ PKA reduced→ Reduced Ca2+ coming in
• G inhibitory proteins (beta and gamma subunit)→ activate K+ channels→ K+ moves out→ cell begin to hyperpolarise→ reduced frequency of action potential → Decreased heart rate→ Decreased CO→ Decreased BP
Cardio inhibitory centre
Cardio inhibitory centre→ has parasympathetic fibers (Dorsal nucleus of vagus)→ innervate SA node
(right vagus) and AV node (left vagus)
Hypertension 2 short term mechanisms
Hypertension - activation of cardio inhibitory centre
Hypertension - inhibition of cardio acceleratory centre
Hypertension - long term compensation
• If there is increased blood pressure→ increase in atrial pressure→ secretes atrial natriutic peptide
(ANP)
• ANP has vasodilator effects:
– Increase venous compliance→ decrease central venous pressure→ reduce ventricular preload→Reduced CO
– Cause arterial vasodilation→ Reduced TPR
• ANP acts as counter regulatory system for renin-angiotensin-aldosterone system (RAAS)
– Inhibits renin synthesis
– Reduced Ang II synthesis→ Reduced aldosterone and ADH synthesis
– Reduce stimulation of hypothalamic thirst centres
– Increased glomerular filtration rate (GFR)→ Increased Na excretion (Natriuresis) and increased fluid excretion (diuresis)
When is anp secreted
• If there is increased blood pressure→ increase in atrial pressure→ secretes atrial natriutic peptide
Factors of hypertension
- Things that affect cardiac output
• Hormones (renal retention
○ Aldosterone, ADH
• Venous tone and contracctility ○ Catecholamines • Heart rate ○ Sympathetic and parasympathetic nervous systems ○ Catecholamines
Factors of hypertension
Things that affect peripheral resistance
• Local regulators – endothelial fucntion
○ Nitric oxide, prostaglandins, endothelian
• Blood viscosity ○ Haematocrit
Factors of hypertension
Anything that impacts cardiac output and peripheral resistance can cause hypertension
Essential hypertension
• High blood pressure with no definable cause
○ It is likely that numerous modulators (obeisty,age, gender, diet etc) controlling BP are defective and this interacts with environmental stressors
Essential hypertension - problem
- Desensititasiton of pressure and volume receptors
- Issues with high catecholamines and adrenal regualtion
- Kidney disfunction – ion channel defects
- Endothelial dysfunction
- Heart – high CO
Secondary hypertension
Hyperiension with definable cause
• Intervention is important – Prevents adaptation which may be irreversible
Secondary hypertension - risk factors
– Age – Development of hypertension <20 years or >50 years
– Severity – More severe rises in BP are related to secondary hypertension
– Onset – Present abruptly rather than progressively
– Family history – Sporadic
History taking is important when diagnosing secodnary hypertension
Causes of secondary hypertension
- Chronic renal disease – increased creatinine, abnormal urinalysis
- Primary aldosteronism – drop in potassium
- Renovascular
- Pheochromocytoma
- Coarctation of the aorta cushing syndrome
Consequences of hypertension
Heart
• Left ventricular hypertrophy
• Heart failue
• Myocardial ischaemia and infarction
Cerebrovascualr
• Stroke
Aorta and peripheral vascular
• Aortic aneurysm and/or dissection
• arteriosclerosis
Kidney
• Nephrosclerosis
• Renal failure
Retina
• Arterial narrowing
• Haemorrhages, exudates, papilledema
Raas summary
- JG cells produce renin→ converts angiotensinogen to Ang I
- Ang I converted to Ang II by ACE in lungs
- Ang II stimulate zona glomerulosa cells to release Aldosterone (increase Na+ reabsorption)
- Ang II stimulates supraoptic nucleus of hypothalamus to release ADH (increase water reabsorption)
- Ang II stimulated hypothalamic thirst centres
- Ang II can cause vasocontriction
Action potentials in CVS
—> transient shift in RMP by movement of ions
Ventricular action potential phases
- Phase 0 = inward movement of sodium through voltage gated sodium channels
- Phase 1 = transient repolarisation, due to movement of transient potassium current out of cell
- Phase2 = plateau, calcium movement into cell – voltage gated calcium channels
- Phase 3= repolarisation, return to RMO by slow movement of potassium out of cells
- Phase 4 = permeability of cardiomyocytes to potassium at rest
Hyperkalaemia
—> serum potassium conc > 5.5mmol/L
3 effects of hyperkalaemia
- RMP depolaraisation - RMP becomes less negative
- Effect phase 0 = rapid depolaraisation becomes a lot more sluggish and slow
- Action potential duration shortening (due to problem with repolarisation)
Hyperkaldemia
• RMP depolaraisation - RMP becomes less negative
○ Due to permeability of cardiomyocyte cell membrane to potassium at rest,
when extracellular potassium is higher, less potassium ions move out of the cell into the exterior,
so the cell interior becoems more positve meaning RMP is less negative
Hyperkalaemia
• Effect phase 0 = rapid depolaraisation becomes a lot more sluggish and slow
○ Changes ion conductance velocity = Over 8mmol/L of potassium conc conduction velocity slows because membrane potential becomes more positive due to hgih extracellular potassium, this inactivates sodium voltage gated channels
Can get so bad to cause asytole
Hyperkalaemia
• Action potential duration shortening (due to problem with repolarisation)
○ Due to phase 3 potassium channels responding to hyperkalaemia, higher extracellular potassium conc than normal, so potassium channels responsible for phase 3 increase conductance (and even though conc gradient is lower) these ion channels are more likely to conduct current
= speeds up repolaraisation so action potential duration is shorter
Hyperkalaemia - causes
- Chronic and acute renal failure
* Potassium supplementation
3 effects of hypokalaemia
- RMP hyperpolarisation = RMP becomes more positive
- Inhibition of sodium and potassium atpases
- Action potential duration prolongation (ap gets longer)
- Delayed early after depolaraisation – dashed orange line
Hypokalaemia
• RMP hyperpolarisation = RMP becomes more positive
○ Greater than normal conc gradient, so more potassium moves out of cell down conc gradient, cell interior becomes slightly more negatively charged compared to cell exterior
Hypokalaemia
• Action potential duration prolongation (ap gets longer)
○ Low extracellular potassium conc increases conc gradient but during hypokaalemia the potassium channels in phase 3 repolarisation are blocked by cations and proteins and prevent movement of potassium out of these channels down conc gradient = as potassium channels aren’t working properly it takes much longer for repolarisation to occur.
Hypokalaemia
• Delayed early after depolaraisation – dashed orange line
○ Caused by oscillations in membrane potentiald ue to action potential prolongation = can cause ventricular fibrilation which is a loss of cardiac output that can casue death
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