18. ANS Pt 1 Flashcards
(38 cards)
1
Q
What is role of ANS?
A
- 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)
2
Q
(T/F) Unregulated + prolonged sympathetic state can cause end organ dysfunction.
A
True.
3
Q
What molecules regulate PNS + SNS?
A
- SNS: epinephrine + related molecules (dopamine, norepi)
- PNS: ACh
4
Q
Which responds faster? PNS or SNS?
A
SNS. Sympathetic burst followed by slow return to homeostatic state.
5
Q
(T/F) An increase in epi is equivalent to a decrease in PNS?
A
True
6
Q
Describe adaptive + maladaptive ANS.
A
- 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
7
Q
What cardiac problems appear in maladapted, unregulated, hypersympathetic state?
A
- Diastolic dysfunction (heart doesn’t relax + fill well)
- Tachycardia
- Tachyarrhymthias
- Ischemia (leading to necrosis)
- Cardiac stunning (heart doesn’t pump well)
8
Q
What pulmonary problems appear in maladapted, unregulated, hypersympathetic state?
A
- 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)
9
Q
What hematologic problems appear in maladapted, unregulated, hypersympathetic state?
A
- Hypercoagulation
- Anemia
- Bone marrow suppression (leading to decreased production of WBC + RBC –> anemia)
10
Q
What endocrinological problems appear in maladapted, unregulated, hypersympathetic state?
A
- 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)
11
Q
What gastroinestinal problems appear in maladapted, unregulated, hypersympathetic state?
A
- 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
12
Q
What immunological problems appear in maladapted, unregulated, hypersympathetic state?
A
- Immune suppresion
- Stim. of bacterial growth (due to increased cathecholamine + decreased immune syst)
13
Q
What metabolic problems appear in maladapted, unregulated, hypersympathetic state?
A
- 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
14
Q
What muscular problems appear in maladapted, unregulated, hypersympathetic state?
A
- Cellular death (use aa to prod more glu)
- Apoptosis (can lead to muscle wasting + weakness if cells don’t regen.)
15
Q
How is ANS organized?
A
-
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
16
Q
What is a second way of generating sympathetic response outside of ANS?
A
Through medulla of adrenal glands, which secrete catecholamines (epi/norepi) during stress –> global response
17
Q
Where does SNS preganglionic nerves originate?
A
Spinal cord between T1-L2, from intermediolateral nuclei (intermediate, lateral part of vertebra where pre-ganglionic nerve originates)
18
Q
What is the NT used for both SNS + PNS at the ganglion?
A
ACh
19
Q
What happens when you give an injection of ACh?
A
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)
20
Q
(T/F) Somatic motor nerves are 2 nerve systems.
A
False. Somatic is 1 nerve system
21
Q
What is the difference in speed between SNS + PNS?
A
- 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)
22
Q
What is the pathway to make epinephrine?
A
- Tyrosine –> –> Dopamine –> Norepiephrine –> Epinephrine
- Not many changes b/w the molecules –> similar responses but different potencies based on what receptors the molecules bind to
23
Q
What are the four types of adrenergic receptors and where is each generally found?
A
-
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
24
Q
What happens when ɑ1 receptors are stimulated?
A
- G protein activation of phospholipase C
- Phosphatidylinositol –> inositol 1,4,5-trisphosphate (IP3) + diacylglycerol (DAG)
- IP3 initiates Ca++ release from ER into cytosol
25
What are the smooth muscle effects of α1 receptor activation?
1. _Eyes_: dilate (constrict muscle) --\> get as much light into eyes as possible to see as much as possible during stressful situation
2. _Lungs_: constrict --\> pulm HTN + bronchoconstriction
* Effects can be overcome by β2 bronchodilation
3. _Blood vessels_: vasoconstriction --\> increased BP
4. _Uterus_: contraction
5. _Genitourinary_: constrict sphinctors
6. _Gut_: constrict sphinctors --\> "stomach in knots" feeling
7. _Endocrine_: inhibits insuline release --\> increased glu in system to be used
* **Insuline** drives glucose into cells to be stored
26
Neosynephrine + norepinephrine are ______ agonists.
α1
27
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
28
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)
29
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
30
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
31
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
32
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
33
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
34
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
35
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
36
How are NT broken down?
1. **Reuptake**: put NT back into storage
2. **Degradation**: degrade in synapse (_catechol-O-methyl transferase_, _monoamine oxidase_, which oxidizes w removal of amine group)
37
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_
38
Summary of receptor, receptor location, agonist/antagonist effects
