question

Catecholamine synthesis occurs in...

answer

all adrenergic nerves and the adrenal medulla

question

The rate-limiting step in the synthesis of catecholamines is the conversion of tyrosine to dopa by ...

answer

Tyrosine Hydroxylase.

question

Tyrosine hydroxylase is subject to...

answer

feedback inhibition by dopamine and norepinephrine. For example, too much NE and Dopamine will inhibit tyrosine hydroxylase activity, thus decreasing catecholamine synthesis. The opposite will also occur, decreased levels of NE and Dopamine leads to increased Tyrosine Hydroxylase activity and increased production of catecholamines

question

Norepinephrine and Epinephrine synthesis in the adrenal medulla __% is epinephrine, __% is norepinephrine.

answer

80;20

question

Phenylalanine is converted into Tyrosine in the...

answer

LIVER.

question

Tyrosine is then collected into the ..

answer

adrenergic nerve terminals.

question

Release of Catecholamines process:

answer

-Catecholamines are accumulated in storage vesicles by active transport. -The vesicles become "docked" near the presynaptic plasma membrane. -After membrane depolarization, calcium influx occurs. -As a result of calcium influx, the vesicle fuses to the presynaptic plasma membrane wall and neurotransmitters are released by exocytosis into the synaptic cleft. This process is Ca++ and ATP dependent. CLNICAL EXAMPLE: Hypocalcemia would be a differential dx for a pt with neuromuscular weakness. -The empty vesicles are recycled.

question

Number one way that catecholamines are removed from synaptic cleft is...

answer

reuptake.

question

Pheo - reuptake info:

answer

A tremendous amounts of catecholamines throughout body, including NMJ. Concept of reuptake is important in pheo because it is the number one way catecholamines go back into storage vesicles. In this picture, instead of 4 NT molecules imagine 10-20. Therefore if a sympathetic response occurred you could imagine the degree of physiologic response that would occur. Therefore, in a patient with pheo, the storage vesicles are considered "loaded".

question

The plasma half-life of catecholamines is ...

answer

less than one minute, broken down rapidly within the liver.

question

Catecholamines are removed from the secretory site in three ways:

answer

1) Reuptake 2) Diffusion away from the synaptic junction 3) Enzymatic breakdown

question

Reuptake: The #1 way in which catecholamines..

answer

...enter the storage vesicles. -50-80% of catecholamines are recycled via this method. It is an active transport process (ATP used). In a pt with Pheo vesicles are "loaded" with catecholamines.

question

Diffusion of catecholamines away from synaptic junction into tissues and plasma: Diffusion after ...

answer

...unbinding from the postsynaptic receptors and will then diffuse into tissues and plasma, eventually being broken down by liver and/or kidneys

question

Enzymatic breakdown of catecholamines occurs via:

answer

MAO and COMT

question

Monoamine oxidase (MAO):

answer

**A pre-synaptic tissue based enzyme system. Breakdown occurs via deamination (removal of amine group from catecholamine), rendering it physiologically inactive.

question

Catechol-O-methyltransferase (COMT):

answer

A blood borne enzyme, highest concentrations are located in kidneys and liver. COMT utilizes oxidation to break down catecholamines.

question

Metabolites from catecholamine enzymatic breakdown can be measured ...

answer

in the blood and urine; this is used to diagnose a pheochromocytoma

question

In the pre-synaptic membrane, MAO metabolizes epinephrine and norepinephrine into

answer

vanillymandelic acid (VMA).

question

VMA is the ...

answer

common final product from the breakdown of catecholamines.

question

In the liver, epinephrine is metabolized by...

answer

COMT into metanephrines and norepinephrine is metabolized by COMT into normetanephrines. Both end up as VMA as the final product. VMA, normetanephrine and metanephrine are measured in pts with pheo. -These end products of catecholamine metabolism are excreted in the urine and can also be found in the blood.

question

MAO inhibitors are used to treat patients with...

answer

depression and other mental illnesses. -A decreased # of neurochemicals may be the cause of depression, specifically catecholamines in the brain. -Therefore, an MAO inhibitor is used to increase the amount of catecholamines available.

question

An herbal MAO inhibitor is ...

answer

St. Johns Wart. During surgical stimulus a pt on MAOIs may exhibit a hyperdynamic response resulting in a hypertensive crisis. Not prescribed often 2/2 this side effect. New MAOIs coming out that target sub-types to avoid these SEs.

question

Alpha 1 Receptors:

answer

-Postsynaptic adrenoreceptors located in the smooth (vascular) muscle throughout the body.

question

Agonism of alpha 1 receptors results in:

answer

increased BP by increasing vascular resistance example: Neosynephrine. Antagonism results in: vasodilation and decreased BP. -In pheo the majority of chemical released is NE, 90% of pheos are predominantly NE secreting tumors. One of the major signs of pheo is "incredibly" high blood pressure. Pre-operatively we treat these pts with alpha-1 blockers in attempt to normalize their BP.

question

Alpha 2 Receptors:

answer

-Presynaptic adrenoreceptors located in the CNS. -Agonism results in: Decreased SNS outflow example: Clonidine. Later we will discuss Clonidine with the suppression test that works as an alpha-2 agonist.

question

Beta 1 Receptors:

answer

-Postsynaptic adrenoreceptors located mainly in the heart. -Agonism results in: Increased HR, contractility, and chronotropy (increased rate of cardiac impulse conduction).

question

Due to baroreceptor response pts frequently become ___________ after receiving alpha-1 blockade.

answer

tachycardic

question

Beta 2 Receptors:

answer

-Postsynaptic adrenoreceptors located mainly in smooth muscle and glands. -Agonism results in: Relaxation of the bronchi and vasculature. Antagonism results in the opposite

question

Lungs: In pheo ...

answer

NE will result in alpha 1 agonism and can result in increased bronchial tone and/or bronchoconstriction.

question

Pancreas: in pheo

answer

Alpha-1 effect is to decrease insulin secretion.

question

Liver: in pheo

answer

Alpha-1 effect is to increase the break down of glycogen to increase BS. -In a very active tumor the alpha-1 effects will greatly overshadow the B2 effects because NE is the main culprit. -Therefore net effect (decreased insulin, increased glycogen breakdown) increased BS (concern pre-op).

question

**______ blockers MUST be given before ____ blockers (A before B)**

answer

alpha;beta -If we were to give beta blockers first ex. Propranolol (Inderal), which is not beta 1 specific, we would have unopposed alpha-1 constriction leading to a hypertensive crisis.

question

How does upregulation or down regulation happen?

answer

-Catecholamines exert their pharmacological actions by causing a conformational change in an adrenergic receptor. -Receptor activation of G proteins then increases cAMP concentrations. This change increases phosphorylation within the cell and the main effect is typically increased amounts of intracellular Ca++, leading to a physiologic response. -The effector proteins cause changes in cellular dynamics. -Depending on the amount of catecholamines released, adrenergic receptors become sensitized (up-regulation) or desensitized (down-regulation). -There is an inverse relationship between receptor sensitization and amount of catecholamines.

question

Remember when we talk about receptor up-regulation and down-regulation we're talking about....

answer

"functional tolerance"

question

Increased catecholamines, receptor desensitization =

answer

down-regulation

question

Decreased catecholamines, receptor sensitization =

answer

up-regulation

question

Up-regulation of adrenoreceptors can occur very ...

answer

rapidly, for example research has shown it to occur as soon as 30 minutes after a spinal cord injury. CLINICAL EXAMPLE: This is why patients must be gradually weaned off of beta-blockers, to avoid a potential ischemic event. The beta-blocker that was being taken by the patient blocks adrenoreceptors. The tissue, specifically in the heart beta-1 receptors, gets used to little stimulation on beta-blockers and up-regulation occurs. Then if a pt stops cold turkey, you have the increased number of receptors PLUS the receptors no longer being blocked and you can have a patient that has a hypertensive crisis or ischemic event. SIMILAR TO PHEO: Pts with pheo are down-regulated 2/2 to the large amount of NE. When pheo is being removed the source of NE will be removed, however we have loaded these pts pre-operatively with alpha-1 blockers with long ½ lives. The combination of down-regulation, pheo removal, and alpha-1 blockade can render the pt hypotensive post-removal of the pheo.

question

The adrenal glands are composed of the...

answer

outer cortex and inner medulla

question

The adrenal cortex is responsible for ..

answer

synthesis and release of mineralocorticoids, glucocorticoids, and androgens.

question

The adrenal medulla contains ...

answer

glandular cells of sympathetic origin, which are called chromaffin or pheochrome cells. (80% epi 20% NE)

question

The adrenal glands sit ...

answer

on top of each kidney. (So you have two...)

question

The adrenal glands are contained in...

answer

a thin fibrous capsule surrounded by fat.

question

Blood flow is derived from the ...

answer

aorta, inferior phrenic artery, and renal artery. Per gram of tissue they have the highest blood flow in the body.

question

The capillary endothelial lining is ...

answer

in direct contact with the pheochrome cells.

question

Venous return flows from ...

answer

the right adrenal gland to the inferior vena cava, and from the left adrenal gland into the left renal vein.

question

CATECHOLAMINE SURGE WITH

answer

SURGICAL MANIPULATION -Short adrenal veins are hyper-concentrated with catecholamines that enter directly into the central circulation, right up the inferior vena cava. -During surgical manipulation there is the potential for an enormous catecholamine surge into the central circulation and enormous physiologic responses.

question

POTENTIAL FOR

answer

BLEEDING. -The area surrounding the adrenal glands is very vascular and there is the potential for rapid, uncontrolled bleeding. -This procedure can be performed via laparoscopy, however, if bleeding is encountered the potential for blood loss is tremendous before being able to convert to open.

question

The adrenal medulla is innervated by...

answer

preganglionic fibers that bypass the paravertebral ganglia (T1-L2).

question

Since the adrenal medullary tissue is embryologically derived from....

answer

neural tissue, the adrenal medulla acts (as its own) as group of postganglionic neurons (only place in the body where this occurs).

question

The post-synaptic neurotransmitter at end organs for SNS is primarily __, however, for sweat glands it is ___.

answer

NE;Ach

question

Remember that in both the PNS and SNS ___ is the primary pre-synaptic neurotransmitter.

answer

Ach

question

Pheochrom=

answer

staining darkly with chrome salts

question

-A catecholamine-secreting tumor derived from ...

answer

chromaffin cells, frequently located in the adrenal medulla. Incidence is low, 2 in 100,000 people. Thought to be 0.1 to 1% cause of HTN. 90% of pheos originate in the adrenal glands.

question

Because adrenal tissues are embryologically derived from neural tissue, this catecholamine releasing tissue can be in other places (10% incidence) including ...

answer

**intra-abdominal (most common), pelvis, aorta, cervical neck region, mediastinum, vagina, spermatic cord, intrapericardial or intramyocardial, or lastly the bladder wall

question

Organ of Zuckerkandl:

answer

Pheochrome tissue that exists at the bifurcation of the aorta and R/L iliac arteries.

question

What are three locations of Pheos?

answer

-cervical -thoracic -abdominal (70-80%) - Upper Abdomen, Organ of Zuckerkandl, Bladder

question

__% of pheochromocytomas are malignant

answer

10;2/2 genetic mutations and may run in families. If familial then typically (greater than 50% of the time) bilateral adrenal.

question

Genetic predisposition:

answer

runs in families

question

___ of pheos occur in children and most commonly male children. Usually only one adrenal in children.

answer

1/3

question

Pheochromocytomas usually occur between ...

answer

30 and 50 years of age. Rare at age ; 60.

question

Equal frequency between

answer

adult males and females.

question

An association exists between pheochromocytomas and...

answer

multiple endocrine neoplasia 2 (MEN 2) and von Hippel-Landau syndrome (a familial/genetically pre-disposed syndrome where people develop CNS and visceral tumors). -Some pheos are not really active, they do not secret a tremendous amount of catecholamines, however, during a stressful period (pregnancy or even surgery), the catecholamine release can increase. Thus, the first s/sx of pheo can be un-masked during pregnancy and can be misdiagnosed as pre-eclampsia.

question

MEN Type 2A Manifestation

answer

Medullary thyroid cancer, Parathyroid adenoma, Pheochromocytoma

question

MEN Type 2B Manifestation

answer

Medullary thyroid cancer, Mucosal adenomas, Marfan appearance, Pheochromocytoma

question

Von Hippel-Lindau Syndrome Manifestation

answer

Hemangioblastoma involving the CNS, Pheochromocytoma

question

Familial pheochromocytoma occurs bilaterally in __% of cases and is rarely malignant or extra-adrenal.

answer

50

question

Familial pheos=

answer

rarely cancerous

question

5 year survival rate after adrenalectomy for nonmalignant pheochromocytoma is ;__%.

answer

95

question

5 year survival rate after adrenalectomy for malignant pheochromocytoma is ;__%.

answer

-50 The high mortality rate for malignant tumors is attributed to the fact the adrenals receive high blood flow and therefore at great risk for metastasis

question

What are the best tests for pheo?

answer

1) plasma free metanephrines 2) 24 hr urine for catecholamines/metanephrines

question

95% of patients with pheochromocytomas have increased levels of ...

answer

metanephrines ; normetanephrines.

question

VMA screening is the...

answer

least reliable screening.

question

Why is the VMA screening least reliable?

answer

-Many things can increase the amount of circulating catecholamines for example extreme exercise, thus VMA screening is not the best test for the diagnosis of pheo. -If metanephrine levels are elevated, then three 24-hour urine samples are tested for free catecholamines. If all three samples are within normal limits, the patient is not considered to have a pheochromocytoma.

question

What is one disadvantage of urine tests for the dx of pheo?

answer

The tumor may secrete catecholamines intermittently, leading to high and low peaks of catecholamine metabolites. To prevent a potential false negative a 24-hour urine sample tests is utilized.

question

According to Stoelting's Co-Ex Dx, the best screening test is...

answer

urinary metanephrines, the most sensitive is free NE in urine

question

MOST SENSITIVE TEST ....

answer

FREE NOREPINEPHRINE IN THE URINE

question

Plasma catecholamines levels are...

answer

...poor indicators for the diagnosis of pheochromocytoma and should not be used as an initial screening tool. -This is due to the large variability in catecholamine levels with daily activities.

question

What is the suppression test?

answer

-The release of catecholamines from a pheochromocytoma is not mediated by the central nervous system, so the pt may be in bed relaxing. Infection could also cause a surge of catecholamines. -Clonidine (alpha 2 agonist) is administered (0.3 mg) PO. (Decreasing sympathetic output from CNS) If in three hours hypertension is not present, then a pheochromocytoma does not exist. If in three hours hypertension is present a pheochromocytoma may be present.

question

A CT scan can...

answer

...localize 95% of tumors, it can detect adrenal masses as small as 1 cm and if extra-adrenal it can detect masses as small as 2 cm.

question

Signs and symptoms are caused by ...

answer

excessive catecholamine release.

question

Hypertension may be....

answer

sustained or paroxysmal.

question

The triad of________, ________, and __________ may be the most reliable indicator of the presence of a pheochromocytoma.

answer

**headache, diaphoresis, and tachycardia

question

Exacerbations may be caused by a variety of factors including:

answer

psychological stress, infection, physiologic stress (decreased BP, hypothermia, surgical trauma, intubation).

question

During an acute episode the following symptoms may occur:

answer

Think NE. Hypertension, HA, pallor (especially in periphery b/c NE potent vasoconstrictor), palpitations, stroke, MI, ischemic changes.

question

Orthostatic hypotension due to...

answer

plasma fluid deficit associated with polycythemia. (All d/t high SVR). Pheo associated with increased secretion of erythropoietin.

question

Hyperglycemia 2/2 ...

answer

pancreatic response (decreased insulin production/increased glycogen breakdown in liver).

question

Paresthesia and ischemia in ...

answer

extremities.

question

As a result of excess catecholamine levels, the following changes can occur to the heart:

answer

INCREASED SVR -Left ventricular hypertrophy -Ischemia -MI -Cardiomyopathy/CHF -Rhythm disturbances (PVCs)- catecholamines sensitize myocardium to arrhythmias

question

Only __-__% of patients with pheo develop these symptoms. The symptom of bradycardia is rare (3%), however is thought to occur 2/2....

answer

10-30; the baroreceptor response.

question

Treatment includes ...

answer

surgical removal of the pheochromocytoma

question

The goals of preoperative preparation are to...

answer

establish alpha and beta blockade, restore blood volume, assess end organ damage, control hypertension and treat cardiac dysrhythmias.

question

_____ BLOCKADE MUST BE ACCOMPLISHED BEFORE ____ BLOCKADE

answer

alpha; beta

question

Why alpha before beta?

answer

This is done to avoid CHF; if we give a beta-blocker to a pt. with a very high vascular resistance they can develop CFH. Also, "remember that the beta-2 effects have an overall vasodilating effect, therefore if you give a beta-blocker, which is not beta-1 specific, which is also a beta-2 antagonist, you can have unopposed alpha constriction and can make their BP climb higher than it was before pharmacologic therapy was started".

question

Which alpha blockers are given?

answer

Phenoxybenzamine, Prazosin, Doxazosin

question

Phenoxybenzamine:

answer

-The drug of choice. -Given 10-14 days pre-op. -It is both an alpha 1 & 2 antagonist. -It is a non-competitive blocking agent, irreversible bond with adrenergic receptor. ½ life is long (24 hours). -Should be continued all the way up to the day of surgery. Because of alpha blockade a hypotensive event would necessitate higher amounts of pressors, the normal response to pressors is altered when taking phenoxybenzamine. The biggest undesirable effect of phenoxybenzamine is that normal vascular function takes two weeks to return. Other alpha-blockers are not typically used for pheo because they are competitive blocking, these agents would not work effectively with the large amounts of catecholamines competing for the adrenergic receptors.

question

Prazosin:

answer

Alpha-1 competitive blocker with a ½ life of 2-3 hrs.

question

Doxazosin:

answer

Alpha-1 competitive blocker with a longer duration of action. Normal vascular function returns in 24-36 hrs. Some experts suggest that Doxazosins works just as well as phenoxybenzamine while allowing for normal vascular function to return faster.

question

If you alpha block someone who is volume depleted the baroreceptor response is.....

answer

tachycardia, beta blockade must then be initiated.

question

Beta Blockers:

answer

No one beta blocker has been proven to be best for pheo. However, the most commonly used is Inderal (Propranolol) 2/2 to the long duration of action. With the use of beta-blockers you must be vigilant for the risk of CHF, especially with this population

question

Calcium Channel Blockers:

answer

The added effect from this group of drugs is coronary artery dilation

question

Metyrosine:

answer

Inhibits tyrosine hydroxylase and can decrease catecholamine production by 40-80%.

question

Optimal Preoperative Preparation

answer

-**The following criteria must be met prior to surgical intervention** -No BP should exceed 160/90 for 24-48 hrs pre-operatively. -Orthostatic hypotension with BP > 85/45 should be present. -ECG without evidence of ST and/or T wave abnormalities for one week. If present, further work up must be completed (ie ECHO) -No more than one PVC q 5 mins. -HCT should be decreased by 5%, indicating re-hydration. According to Nagelhout & Plaus patients will be less labile if this can be achieved.

question

Goals For Intraoperative Anesthetic Management

answer

-Avoid drugs that cause sympathetic nervous stimulation. -Attempt to decrease sympathetic nervous stimulation without causing hypotension. -Use of vasopressors and vasodilators when necessary. -Direct acting pressors such as Phenylephrine is the pressor of choice. -Use of invasive monitoring. A-line, CVP, if significant cardiac dx then PA cath & CO monitoring

question

**The nurse anesthetist must be aware of the possibility of extreme hypertension during the following 3 times**

answer

1.) During intubation 2.) During manipulation of tumor 3.) Ligation of the venous drainage

question

Preoperative factors that increase the incidence of morbidity/mortality for patients with a pheochromocytoma include:

answer

-A large tumor, they tend to be more active. -Prolonged duration of surgery/anesthesia. -Increased pre-operative catecholamine levels.

question

DRUGS TO AVOID IN A PATIENT WITH PHEOCHROMOCYTOMA

answer

Desflurane Pancuronium Atracurium Succinylcholine Morphine Droperidol Metoclopramide Phenothiazines Ephedrine Ketamine Atropine Narcan

question

General surgical considerations:

answer

-They are working at the level of the 12th rib; the incision is made in the flank. -Whenever they are working at this high of a level the risk of a pneumothorax is possible. -If they are working on the right side it is very close to the liver and if they are working on the left they are very close to the pancreas and the spleen. -The average EBL (open) is 200-300 cc with insensible loses of 10-15 cc/kg/hr. -T&C with blood available and a fluid warmer are essential.

question

Preoperative Medications

answer

Benzodiazepines

question

The goal of induction is to ...

answer

achieve an adequate depth of anesthesia before laryngoscopy and at the same time avoiding hypotension (slow induction- beta-blockers and vasodilators drawn up and readily available)

question

Combined technique with epidural and GA (adv vs disadv)

answer

Advantage: help with post-op pain and BP control prior to tumor removal Disadvantage: once tumor out may have hypotension that is difficult to control

question

Induction meds:

answer

-Sodium pentothal, propofol, or etomidate for induction. -All induction agents would be appropriate except for Ketamine (for obvious reasons)

question

Lidocaine 1-1.5 mg/kg to

answer

decrease SNS response

question

Narcs for induction:

answer

Fentanyl/sufentanil preinduction.

question

For induction and introperative maintenance:

answer

-Vasodilators: The dilator of choice is Nipride because it acts primarily on arteries. -Vasopressors: Direct acting preferred, Neosynephrine.

question

maintance of anesthesia:

answer

-Nitrous oxide and Isoflurane/Sevoflurane. MAC of 1.5-2 may be used if healthy heart. Some people say no nitrous because of potential for pneumo -Narcotics -Non-histamine release inducing muscle relaxants. -Esmolol drip may be desirable 2/2 large and labile swings in BP. -Hypertension with release of catecholamine from tumor manipulation. -If extreme HTN with PVCs develops the recommendation is not to give an antiarrhythmic but to lower the BP in attempt to decrease the work of the heart. -Hypotension after tumor venous ligation is best treated with decreasing depth of anesthesia/increasing fluid administration/direct acting vasopressor. -Hypoglycemia can occur quickly after tumor removal and during post-op period.

question

Factors that can contribute to postoperative hypotension include:

answer

-Volume depletion (along with alpha blockade) -Ischemia/MI -Bleeding -Sepsis

question

Factors that can contribute to postoperative hypertension include:

answer

-Pain -Volume overload -Hypoxia, consider pneumothorax (according to Jaffe it can occur up to 20% of the time). -Hypoglycemia -Residual pheo

question

75% of patients become normotensive within ...

answer

10 days

question

In the remaining 25% of patient's, blood pressure is...

answer

controlled on antihypertensive drug regimen.

question

Alternative Approaches:

answer

Laparoscopic removal of pheochromocytoma has been performed. -Advantages: Small incision site without thoracotomy (decreased post-op pain), Decreased insensible loses and maintenance of their temperature. -Disadvantages: Pneumoperitoneum for 2-3 hours (can pts cardiac status tolerate this?), Ability and time to convert to open procedure if needed. Will not be done via lap if pheo ;10 cm pheo or pheo is known to be cancerous.

question

-Regional anesthesia has been used with success, however disadvantages include:

answer

-Need for a continuous high block. -Difficulty breathing and with positioning (prone or lateral) -Profound hypotension after tumor removal.

question

What is a CT guided percutaneous ethanol injection (This is being done in China):

answer

-A needle bx of the pheo is taken, they will make sure it is not cancerous, infiltrate with LA, and then inject ethanol into the medulla of the adrenal gland. Vascular embolization will occur by ceasing blood flow to the tumor and causing pheo cell death.

question

Alternative Intraoperative Diagnosis:

answer

-If a pheochromocytoma is undetected and a patient is undergoing surgery for another problem, then surgical stress can cause a catecholamine release. -The clinical picture of extreme hypertension, tachycardia, and dysrhythmias may be misdiagnosed as malignant hyperthermia.

Anesthesia case management for the patient with pheochromocytoma – Flashcards

Unlock all answers in this set

Haven't found what you were looking for?

Search for samples, answers to your questions and flashcards