18. ANS Pt 1 Flashcards
What is role of ANS?
- To help the body respond to internal environmental stresses and bring today back down to homeostasis.
- Resting state allows for growth + metabolism
- Reactive state is ineffective + inefficient, damaging to organs
- ANS can respond to real or perceived stresses (emotional stresses (esp. non-physical) that aren’t normally stressful become stressful)
(T/F) Unregulated + prolonged sympathetic state can cause end organ dysfunction.
True.
What molecules regulate PNS + SNS?
- SNS: epinephrine + related molecules (dopamine, norepi)
- PNS: ACh
Which responds faster? PNS or SNS?
SNS. Sympathetic burst followed by slow return to homeostatic state.
(T/F) An increase in epi is equivalent to a decrease in PNS?
True
Describe adaptive + maladaptive ANS.
- Adaptive: typically short lived response of SNS followed by return to homeostasis via PNS.
- Maladaptive: long-lasting, uncontrolled sympathetic state causing chronic stress leading to organ damage + dysfxn
What cardiac problems appear in maladapted, unregulated, hypersympathetic state?
- Diastolic dysfunction (heart doesn’t relax + fill well)
- Tachycardia
- Tachyarrhymthias
- Ischemia (leading to necrosis)
- Cardiac stunning (heart doesn’t pump well)
What pulmonary problems appear in maladapted, unregulated, hypersympathetic state?
- Pulmonary edema (increased outflow cardiac failure w leaky pulm capillaries)
- Maladaptive effects of heart causes decreased CO –> increased P in LV –> increased P in pulmonary veins + capillaries –> fluid into alveoli
- Pulmonary HTN (causes increased RV strain –> fluid back up in periphery –> swelling in extremeties + liver + other tissues)
What hematologic problems appear in maladapted, unregulated, hypersympathetic state?
- Hypercoagulation
- Anemia
- Bone marrow suppression (leading to decreased production of WBC + RBC –> anemia)
What endocrinological problems appear in maladapted, unregulated, hypersympathetic state?
- Decreased thyroid fxn (thyroid releases hormones that regulate growth and rate of fxn for many organ systems –> impt for cellular growth + metabolism)
- Decreased growth hormone (GH impt for long-term cellular growth + short-term tissue repair)
- Glucose intolerance (hyperglycemia)
What gastroinestinal problems appear in maladapted, unregulated, hypersympathetic state?
- Hypoperfusion (leads to ulcers + break down of intestinal walls –> gut bacteria leak through –> sepsis)
- Decreased peristalsis (lim digestion + uptake of nutrients –> malnourished despite eating)
- Ulcerations
What immunological problems appear in maladapted, unregulated, hypersympathetic state?
- Immune suppresion
- Stim. of bacterial growth (due to increased cathecholamine + decreased immune syst)
What metabolic problems appear in maladapted, unregulated, hypersympathetic state?
- Increased cellular metabolism (requires increased O2, nutrients, E, + CO2 removal; if body can’t provide –> cellular death)
- Hyperglycemia (for heart + brain, which primary uses glu for E)
- Catabolism
- Lipolysis
- Electrolyte fluxes
What muscular problems appear in maladapted, unregulated, hypersympathetic state?
- Cellular death (use aa to prod more glu)
- Apoptosis (can lead to muscle wasting + weakness if cells don’t regen.)
How is ANS organized?
-
Two nerve system: pre-glanglionic nerve –> ganglion (where nerve synapses) –> post-ganglionic nerve
- SNS: pre-ganglionic comes from spinal cord, ganglion at symathetic chain (b/w T1-L2) close to cords
- PNS = cranial-sacral system: pre-ganglionic from cranial pt near brainstem + sacral region of cords, ganglion close to innervated organ
- Connects CNS to end organs
What is a second way of generating sympathetic response outside of ANS?
Through medulla of adrenal glands, which secrete catecholamines (epi/norepi) during stress –> global response
Where does SNS preganglionic nerves originate?
Spinal cord between T1-L2, from intermediolateral nuclei (intermediate, lateral part of vertebra where pre-ganglionic nerve originates)
What is the NT used for both SNS + PNS at the ganglion?
ACh
What happens when you give an injection of ACh?
Both SNS + PNS will be upregualted becuase ACh = NT used at ganglion for both systems. However, much harder to get ACh into ganglion than end organ receptors –> greater increase in PNS than SNS –> overall down regulation of SNS (increase in PNS = decrease in SNS)
(T/F) Somatic motor nerves are 2 nerve systems.
False. Somatic is 1 nerve system
What is the difference in speed between SNS + PNS?
- SNS: input tends to be more fast on b/c each nerve innervates one organ
- PNS: ganglions located more in periphery from where nerves branch off before innervating multiple organs –> slower onset
- e.g. During stressful situation, tachycardia appears almost immediately (SNS) but bringing HR back down takes a while (PNS)
What is the pathway to make epinephrine?
- Tyrosine –> –> Dopamine –> Norepiephrine –> Epinephrine
- Not many changes b/w the molecules –> similar responses but different potencies based on what receptors the molecules bind to
What are the four types of adrenergic receptors and where is each generally found?
-
α1 receptors = post-synaptic, located on end organs
- Commonly on smooth muscle, esp of blood vessels
-
α2 receptors = primarily pre-synaptic membrane w some post-synaptic
- Mostly smooth muscle + CNS
-
β1 receptors are post-synaptic
- Primarily on heart
-
β2 receptors are post-synaptic
- Primarily on smooth muscle, esp bronchiole smooth muscle, skeletal muscle, arterioles, + glands
What happens when ɑ1 receptors are stimulated?
- G protein activation of phospholipase C
- Phosphatidylinositol –> inositol 1,4,5-trisphosphate (IP3) + diacylglycerol (DAG)
- IP3 initiates Ca++ release from ER into cytosol
What are the smooth muscle effects of α1 receptor activation?
- Eyes: dilate (constrict muscle) –> get as much light into eyes as possible to see as much as possible during stressful situation
-
Lungs: constrict –> pulm HTN + bronchoconstriction
- Effects can be overcome by β2 bronchodilation
- Blood vessels: vasoconstriction –> increased BP
- Uterus: contraction
- Genitourinary: constrict sphinctors
- Gut: constrict sphinctors –> “stomach in knots” feeling
-
Endocrine: inhibits insuline release –> increased glu in system to be used
- Insuline drives glucose into cells to be stored
Neosynephrine + norepinephrine are ______ agonists.
α1
What happens when presynaptic ɑ2 receptors in the periphery are stimulated?
- Feedback control: release of epi/norepi from presynaptic neuron circles back + binds to ɑ2 receptors
- G-protein mediated inhibition of adenylyl cylase –> fall in second messenger cAMP –> decreases Ca++ in post ganglionic nerve terminals –> inhibits exocytosis of NT
- Decreases amount of epi/norepi that reaches postsynaptic ɑ1 receptors –> decreased symathetic tone –> indirect vasodilation
- Epi/norepi are both agonists of ɑ2 receptors leading to their own down regualtion
What happens when postsynaptic ɑ2 receptors are stimulated?
- Smooth muscle: contristrion, similar to ɑ1 effects
- CNS: sedation, reduced CNS output via inhibitory effect (decreased release of NT in CNS)
What is clonidine?
- Selective for ɑ2 receptors in CNS (brain) –> decreases ANS output –> decreased sympathetic tone –> decreased smooth muscle contraction + decreased BP
- Antihypertensive
- Negative chronotrope (brady due to increased vagal stim to SA node due to sympathetic withdrawl)
- Sedative –> decreases anesthetic + analgesic requirements
What is dexmedetomidine/precedex?
- Lipophylic derivative, highly selective ɑ2 receptor agonist –> decreased CNS NT release
- Sedation
- Analgesic
- Sympatholytic –> brady, negative chronotrope
- No respiratory depression + hypotension
What happens when β1 receptors are stimulated?
- Increased adenylyl cylase activity –> increased second messenger cAMP –> increased intracellular Ca++
- Chronotropic: increased rate
- Dromotropic: increased conduction
- Inotropic: increased F of contraction
What happens when β2 receptors are stimulated?
- G-protein increases adenylyl cylase activity –> increased cAMP –> activates various proteins
- Has more of an inhibitory effect on smooth muscle contraction
- Relaxes smooth muscle
- Gluconeogensis (making glu from non-carbohydrate C sources)
- Insulin release (stores glu as glycogen or fat)
- Stim. Na-K pump to drive K intracellular
- Think pumpkin –> Pump-K-in
- Can give to pt w hyperK
What is the diff in affinity to epi/norepi b/w ɑ1 + ɑ2 receptors?
- ɑ1 respond better to norepi than epi
- Smooth muscle cells in vascular system in resp to ɑ1 receptors = excitatory –> vascular smooth muscle contraction –> increase BP
- ɑ2 are inhibitory when stimulated –> decreased release of NT or glandular product (e.g. insulin from pancreas)
- HOWEVER, postsynaptic ɑ2 receptors on vascular smooth muscle behave in similar way at ɑ1 receptors –> vasoconstriction
What receptors do these adrenergic agonists bind to?
- Phenylephrine
- Epinephrine
- Ephedrine
- Dopamine
- Dobutamine
- Albuterol
- Methyldopa
- Clonidine
- Terbutaline
- Fenoldopam
- Phenylephrine - ɑ1
- Methyldopa - ɑ2
- Clonidine - ɑ2
- Dobutamine - β1
- Albuterol - β2
- Terbutaline - β2
- Epinephrine - ɑ + β
- Ephedrine - ɑ + β
- Dopamine - dopaminergic receptors
- Fenoldopam –> vasoconstriction
What is the diff b/w direct + indirect adrenergic agonists?
- Direct: looks like catecholamines, stim. receptor directly
-
Indirect: depends on body’s stores of NT in nerve cell, increase endogenous NT
- Increased release
- Decreased uptake
- Inhibit metabolism
- E.g. ephedrine –> norepi release
- E.g. when someone uses cocaine, depletes body of catecholamines (epi + norepi) such that indirect agonsts have no effect
How are NT broken down?
- Reuptake: put NT back into storage
- Degradation: degrade in synapse (catechol-O-methyl transferase, monoamine oxidase, which oxidizes w removal of amine group)
What are MAO inhibitors?
- Blocks metabolism of catecholamines –> prolonged + pronounced response from SNS, esp w indirect agonists
- Pt taking MAO inhibitors can have huge swings in SNS response
Summary of receptor, receptor location, agonist/antagonist effects
