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Question 1

Elaborate on the location and names of the sympathetic ganglia. Practically speaking, what is the importance of knowing the name and location of these ganglia?

Answer 1

Easily identifiable paravertebral ganglia are found in the cervical region (including the stellate ganglion) and along thoracic, lumbar, and pelvic sympathetic trunks.

Prevertebral ganglia are named in relation to major branches of the aorta and include the celiac, superior and inferior mesenteric, and renal ganglia.

Terminal ganglia are located close to the organs that they serve.

The practical significance of knowing the location of some of these ganglia is that local anesthetics can be injected in the region of these structures to ameliorate sympathetically mediated pain.

Question 2

Review the anatomy and function of the parasympathetic nervous system.

Answer 2

Preganglionic parasympathetic neurons originate from cranial nerves III, VII, IX, and X and sacral segments 2-4.

Preganglionic parasympathetic neurons synapse with postganglionic neurons close to the targeted end-organ, creating a more discrete physiologic effect.

Both preganglionic and postganglionic parasympathetic neurons release acetylcholine; these cholinergic receptors are subclassified as either nicotinic or muscarinic.

The response to cholinergic stimulation is summarized in Table 1-3.

Question 3

Review the synthesis of dopamine, norepinephrine, and epinephrine.

Answer 3

The amino acid tyrosine is actively transported into the adrenergic presynaptic nerve terminal cytoplasm, where it is converted to dopamine by two enzymatic reactions: hydroxylation of tyrosine by tyrosine hydroxylase to dopamine and decarboxylation of dopamine by aromatic L-amino acid decarboxylase.

Dopamine is transported into storage vesicles, where it is hydroxylated by dopamine b-hydroxylase to norepinephrine.

Epinephrine is synthesized in the adrenal medulla from norepinephrine through methylation by phenylethanolamine N-methyltransferase (Figure 1-2).

Question 4

How is noradrenaline metabolized?

Answer 4

Norepinephrine is removed from the synaptic junction by reuptake into the presynaptic nerve terminal and metabolic breakdown. Reuptake is the most important mechanism and allows reuse of the neurotransmitter. The enzyme monoamine oxidase (MAO) metabolizes norepinephrine within the neuronal cytoplasm; both MAO and catecholamine O–methyltransferase (COMT) metabolize the neurotransmitter at extraneuronal sites. The important metabolites are 3-methoxy-4-hydroxymandelic acid, metanephrine, and normetanephrine.

Question 5

describe synthesis and degradation of ACh?

Answer 5

The cholinergic neurotransmitter acetylcholine (ACh) is synthesized within presynaptic neuronal mitochondria by esterification of acetyl coenzyme A and choline by the enzyme choline acetyltransferase; it is stored in synaptic vesicles until release. After release, ACh is principally metabolized by acetylcholinesterase, a membrane-bound enzyme located in the synaptic junction. Acetylcholinesterase is also located in other nonneuronal tissues such as erythrocytes.

Question 6

Review the mechanism of action for b1-antagonists and side effects.

Answer 6

b1-Blockade produces negative inotropic and chronotropic effects, decreasing cardiac output and myocardial oxygen requirements. b1-Blockers also inhibit renin secretion and lipolysis. Since volatile anesthetics also depress contractility, intraoperative hypotension is a risk. b-Blockers can produce atrioventricular block. Abrupt withdrawal of these medications is not recommended because of up-regulation of the receptors; myocardial ischemia and hypertension may occur. b-Blockade decreases the signs of hypoglycemia; thus it must be used with caution in insulin-dependent patients with diabetes. b-Blockers may be cardioselective, with relatively selective B1 antagonist properties, or noncardioselective. Some b-Blockers have membranestabilizing (antiarrhythmic effects); some have sympathomimetic effects and are the drugs of choice in patients with left ventricular failure or bradycardia. b-Blockers interfere with the transmembrane movement of potassium; thus potassium should be infused with caution. Because of their benefits in ischemic heart disease and the risk of rebound, b-blockers should be taken on the day of surgery.

Question 7

Review the effects of b2-antagonism.

Answer 7

b2-Blockade produces bronchoconstriction and peripheral vasoconstriction and inhibits insulin release and glycogenolysis. Selective b1-blockers should be used in patients with chronic or reactive airway disease and peripheral vascular disease because of respective concerns for bronchial or vascular constriction.

Question 8

How might complications of b-blockade be treated intraoperatively?

Answer 8

Bradycardia and heart block may respond to atropine; refractory cases may require the b2-agonism of dobutamine or isoproterenol. Interestingly, calcium chloride may also be effective, although the mechanism is not understood. In all cases expect to use larger than normal doses.

Question 9

Review a2-agonists and their role in anesthesia.

Answer 9

When stimulated, a2-receptors within the CNS decrease sympathetic output. Subsequently, cardiac output, systemic vascular resistance, and blood pressure decrease. Clonidine is an a2-agonist used in the management of hypertension. It also has significant sedative qualities. It decreases the anesthetic requirements of inhaled and intravenous anesthetics. It has also been used intrathecally in the hopes of decreasing postprocedural pain, but unacceptable hypotension is common after intrathecal administration, limiting its usefulness. Clonidine should be continued perioperatively because of concerns for rebound hypertension.

Question 10

Discuss muscarinic antagonists and their properties.

Answer 10

Muscarinic antagonists, also known as anticholinergics, block muscarinic cholinergic receptors, producing mydriasis and bronchodilation, increasing heart rate, and inhibiting secretions.

Centrally acting muscarinic antagonists (all nonionized, tertiary amines with the ability to cross the blood-brain barrier) may produce delirium.

Commonly used muscarinic antagonists include atropine, scopolamine, glycopyrrolate, and ipratropium bromide.

Administering muscarinic antagonists is a must when the effect of muscle relaxants is antagonized by acetylcholinesterase inhibitors, lest profound bradycardia, heart block, and asystole ensue.

Glycopyrrolate is a quaternary ammonium compound, cannot cross the blood-brain barrier, and therefore lacks CNS activity. When inhaled, ipratropium bromide produces bronchodilation.

Question 11

What is the significance of autonomic dysfunction? How might you tell if a patient has autonomic dysfunction?

Answer 11

Patients with autonomic dysfunction tend to have severe hypotension intraoperatively.

Evaluation of changes in orthostatic blood pressure and heart rate is a quick and effective way of assessing autonomic dysfunction.

If the autonomic nervous system is intact, an increase in heart rate of 15 beats/min and an increase of 10 mm Hg in diastolic blood pressure are expected when changing position from supine to sitting.

Autonomic dysfunction is suggested whenever there is a loss of heart rate variability, whatever the circumstances.

Autonomic dysfunction includes vasomotor, bladder, bowel, and sexual dysfunction.

Other signs include blurred vision, reduced or excessive sweating, dry or excessively moist eyes and mouth, cold or discolored extremities, incontinence or incomplete voiding, diarrhea or constipation, and impotence.

Although there are many causes, it should be noted that people with diabetes and chronic alcoholics are patient groups well known to demonstrate autonomic dysfunction.

Question 12

What is a pheochromocytoma, and what are its associated symptoms? How is pheochromocytoma diagnosed?

Answer 12

Pheochromocytoma is a catecholamine-secreting tumor of chromaffin tissue, producing either norepinephrine or epinephrine.

Most are intra-adrenal, but some are extra-adrenal (within the bladder wall is common), and about 10%are malignant.

Signs and symptoms include paroxysms of hypertension, syncope, headache, palpitations, flushing, and sweating.

Pheochromocytoma is confirmed by detecting elevated levels of plasma and urinary catecholamines and their metabolites, including vanillylmandelic acid, normetanephrine, and metanephrine.

Question 13

Review the preanesthetic and intraoperative management of pheochromocytoma patients.

Answer 13

These patients are markedly volume depleted and at risk for severe hypertensive crises.

It is absolutely essential that before surgery, a-blockade and rehydration should first be instituted.

The a1-antagonist phenoxybenzamine is commonly administered orally.

b-Blockers are often administered once a-blockade is achieved and should never be given first because unopposed a1-vasoconstriction results in severe, refractory hypertension.

Labetalol may be the b-blocker of choice since it also has a-blocking properties.

Intraoperatively intra-arterial monitoring is required since fluctuations in blood pressure may be extreme.

Manipulation of the tumor may result in hypertension.

Intraoperative hypertension is managed by infusing the a-blocker phentolamine or vasodilator nitroprusside.

Once the tumor is removed, hypotension is a risk, and fluid administration and administration of the a-agonist phenylephrine may be necessary.

Central venous pressure monitoring will assist with volume management.

Question 14

Major causes of an anion gap metabolic acidosis

Answer 14

These patients are markedly volume depleted and at risk for severe hypertensive crises. It is absolutely essential that before surgery, a-blockade and rehydration should first be instituted. The a1-antagonist phenoxybenzamine is commonly administered orally. b-Blockers are often administered once a-blockade is achieved and should never be given first because unopposed a1-vasoconstriction results in severe, refractory hypertension. Labetalol may be the b-blocker of choice since it also has a-blocking properties. Intraoperatively intra-arterial monitoring is required since fluctuations in blood pressure may be extreme. Manipulation of the tumor may result in hypertension. Intraoperative hypertension is managed by infusing the a-blocker phentolamine or vasodilator nitroprusside. Once the tumor is removed, hypotension is a risk, and fluid administration and administration of the a-agonist phenylephrine may be necessary. Central venous pressure monitoring will assist with volume management.

Question 15

What are the common causes of respiratory acid-base disorders?

Answer 15

n Respiratory alkalosis:

• Sepsis,
• hypoxemia,
• anxiety,
• pain,
• central nervous system lesions n

Respiratory acidosis:

• Drugs (residual anesthetics, residual neuromuscular blockade, benzodiazepines, opioids),
• asthma,
• emphysema,
• obesity-hypoventilation syndromes,
• central nervous system lesions (infection, stroke)
• neuromuscular disorders

Question 16

12. List the major consequences of acidemia.

Answer 16

Severe acidemia is defined as blood pH

Question 17

List the major consequences of alkalemia.

Answer 17

Severe alkalemia is defined as blood pH >7.60 and is associated with the following major effects:

• n Increased cardiac contractility until pH >7.7, when a decrease is seen
• n Refractory ventricular arrhythmias
• n Coronary artery spasm/vasoconstriction
• n Vasodilation of the pulmonary vasculature, leading to decreased pulmonary vascular resistance
• n Hypoventilation (which can frustrate efforts to wean patients from mechanical ventilation)
• n Cerebral vasoconstriction
• n Neurologic manifestations such as headache, lethargy, delirium, stupor, tetany, and seizures
• n Hypokalemia, hypocalcemia, hypomagnesemia, and hypophosphatemia
• n Stimulation of anaerobic glycolysis and lactate production

Question 18

Major causes of a NONanion gap metabolic acidosis

Answer 18

Nonanion gap metabolic acidosis results from loss of Na and K or accumulation of Cl.

The result of these processes is a decrease in HCO3 :

• n Iatrogenic administration of hyperchloremic solutions (hyperchloremic metabolic acidosis)
• n Alkaline gastrointestinal losses
• n Renal tubular acidosis
• n Ureteric diversion through ileal conduit
• n Endocrine abnormalities

Question 19

List the common causes of a metabolic alkalosis.

Answer 19

Metabolic alkalosis is commonly caused by

• vomiting,
• volume contraction (diuretics, dehydration),
• alkali administration,
• endocrine disorders.

Question 20

List the common causes of elevated and nonelevated anion gap metabolic acidosis.

Answer 20

n Nonelevated AG metabolic acidosis is caused by iatrogenic administration of hyperchloremic solutions (hyperchloremic metabolic acidosis), alkaline gastrointestinal losses, renal tubular acidosis (RTA), or ureteric diversion through ileal conduit.

Excess administration of normal saline is a cause of hyperchloremic metabolic acidosis. n

Elevated AG metabolic acidosis is caused by accumulation of lactic acid or ketones, poisoning from toxins (e.g., _ethanol, methanol, salicylates, ethylene glycol, propylene glyco_l) or uremia.

Question 21

Describe the dynamics of fluid distribution between the intravascular and interstitial compartments.

Answer 21

The intravascular and interstitial fluid spaces compose the extracellular fluid and are in dynamic equilibrium, governed by hydrostatic and oncotic forces.

Under normal circumstances the capillary hydrostatic pressure produces an outward movement of fluid, whereas the capillary oncotic pressure results in resorption.

The sum of the forces leads to an egress of fluids from arterioles; about 90% of the fluid returns into the venules.

The remainder of the fluid is subsequently returned to the circulation via the lymphatic system.

Question 22

How are body water and tonicity regulated?

Answer 22

Antidiuretic hormone (ADH) is a primary mechanism;

it circulates unbound in plasma, has a half-life of roughly 20 minutes, and increases production of cyclic adenosine monophosphate in the distal collecting tubules of the kidney.

Tubular permeability to water increases, resulting in conservation of water and sodium and production of concentrated urine.

Stimuli for the release of ADH include the following:

n Hypothalamic osmoreceptors have an osmotic threshold of about 289 mOsm/kg. Above this level ADH release is stimulated.

n Hypothalamic thirst center neurons regulate conscious desire for water and are activated by an increase in plasma sodium of 2 mEq/L, an increase in plasma osmolality of 4 mOsm/L, and loss of potassium from thirst center neurons and angiotensin II.

n Aortic baroreceptors and left atrial stretch receptors respond to volume depletion and stimulate hypothalamic neurons.

Question 23

What is diabetes insipidus?

Answer 23

Diabetes insipidus (DI) is caused by a

deficiency of ADH synthesis,

impaired release of ADH from the neurohypophysis (neurogenic DI),

or renal resistance to ADH (nephrogenic DI).

The result is excretion of large volumes of dilute urine, which, if untreated, leads to dehydration, hypernatremia, and serum hyperosmolality.

The usual test for DI is cautious fluid restriction.

The inability to decrease and concentrate urine suggests the diagnosis, which may be confirmed by plasma ADH measurements.

Administration of aqueous vasopressin tests the response of the renal tubule. If the osmolality of plasma exceeds that of urine after mild fluid restriction, the diagnosis of DI is suggested.

Question 24

Define the syndrome of inappropriate antidiuretic hormone release. What is the primary therapy?

Answer 24

Hypotonicity caused by the nonosmotic release of ADH, which inhibits renal excretion of water, typifies the syndrome of inappropriate antidiuretic hormone (SIADH) release.

Three criteria must be met to establish the diagnosis of SIADH:

n The patient must be euvolemic or hypervolemic.

n The urine must be inappropriately concentrated (plasma osmolality 100 mOsm/kg).

n Renal, cardiac, hepatic, adrenal, and thyroid function must be normal.

The primary therapy for SIADH is water restriction. Postoperative SIADH is usually a temporary phenomenon and resolves spontaneously. Chronic SIADHmay require the addition of demeclocycline,which blocks the ADH-mediatedwater resorption in the collecting ducts of the kidney.

Question 25

What disorders are associated with SIADH?

Answer 25

Central nervous system events are frequent causes, including acute intracranial hypertension, trauma, tumors, meningitis, and subarachnoid hemorrhage.

Pulmonary causes are also common, including tuberculosis, pneumonia, asthma, bronchiectasis, hypoxemia, hypercarbia, and positive-pressure ventilation.

Malignancies may produce ADH-like compounds.

Adrenal insufficiency and hypothyroidism also have been associated with SIADH.

Question 26

What is aldosterone? What stimulates its release? What are its actions?

Answer 26

Aldosterone, a mineralocorticoid, is responsible for the precise control of sodium excretion.

A decrease in systemic or renal arterial blood pressure, hypovolemia, or hyponatremia leads to release of renin from the juxtaglomerular cells of the kidney.

Angiotensinogen, produced in the liver, is converted by renin to angiotensin I. In the bloodstream angiotensin I is converted to angiotensin II, and the zona glomerulosa of the adrenal cortex is then stimulated to release aldosterone.

An additional effect of angiotensin II is vasoconstriction.

Aldosterone acts on the distal renal tubules and cortical collecting ducts, promoting sodium retention. In addition to hyponatremia and hypovolemia, stimuli for aldosterone release include hyperkalemia, increased levels of adrenocorticotropic hormone, and surgical stimulation.

Question 27

What situations might be appropriate for the use of hypertonic saline?

Answer 27

Hypertonic saline (usually 3%) has been used successfully during aortic reconstructions and extensive cancer resections; for hypovolemic shock, slow correction of symptomatic chronic hyponatremia, transurethral resection of the prostate syndrome, and increased intracranial pressure; and to reduce peripheral edema after major fluid resuscitations.

It has been used in far forward combat situations and in trauma patients with prolonged transportation times (rural areas), but its use is still not extremely common.

Question 28

What clinical findings support a diagnosis of hypervolemia?

Answer 28

The patient may have rales on lung auscultation, frothy secretions in the endotracheal tube, edematous mucous membranes and conjunctiva (although edematous conjunctiva by itself is not enough to make the diagnosis, especially when the patient has been in the prone position), polyuria, and peripheral edema.

Like hypovolemia, hypervolemia is best diagnosed when a constellation of findings, and not just a single finding, is present.

Question 29

Review the major transfusion-related reactions.

Answer 29

n Hemolytic transfusion reactions caused by ABO incompatibility are most commonly caused by clerical errors and transfusion of the wrong unit. Mistransfusion is thought to occur with a frequency between 1:14,000 and 1:18,000. Most reactions occur during or shortly after a transfusion. Clinical manifestations include fever; chills; chest, flank, and back pain; hypotension; nausea; flushing; diffuse bleeding; oliguria or anuria; and hemoglobinuria. General anesthesia may mask some of the clinical manifestations, and hypotension, hemoglobinuria, and diffuse bleeding may be the only signs. It should be noted that the signs of a severe hemolytic reaction might be missed while the patient is under general anesthesia or attributed to another cause. n Anaphylactic reactions are caused by binding of IgE; present with bronchospasm, edema, redness, and hypotension; and require urgent treatment with epinephrine, fluid infusions, corticosteroids and antihistamines, and other therapies as indicated by severity and progression of symptoms. n Febrile reactions may be an early sign of hemolytic transfusion reaction (but other symptoms should be present) or bacterial contamination of the blood product. Febrile nonhemolytic transfusion reactions usually occur in patients who have had prior transfusions; headache, nausea, and malaise are associated symptoms. The reaction is caused by leukocyte antibodies, and leukocyte-depleted red blood cells may be indicated for these patients. Antipyretics may decrease the symptoms if given before the transfusion; meperidine may decrease the severity of chills. n Transfusion-related acute lung injury (TRALI) is in the top three of transfusion-related deaths, having a mortality of 50%. A form of noncardiogenic pulmonary edema, TRALI is also immune related and is usually noted within 6 to 12 hours after transfusion. Symptoms include hypoxia, dyspnea, fever, and pulmonary edema; treatment is supportive. n Urticarial reactions secondary to mast cell degranulation do not require that the transfusion be stopped; antihistamines may be given. n These transfusion reactions are compared in Table 6-1.