108 PART 2 Cardinal Manifestations and Presentation of Diseases

Echocardiography Echocardiography (nonstress) is not necessarily routine in patients with chest discomfort. However, in patients

with an uncertain diagnosis, particularly those with nondiagnostic

ST elevation, ongoing symptoms, or hemodynamic instability,

detection of abnormal regional wall motion provides evidence of

possible ischemic dysfunction. Echocardiography is diagnostic in

patients with mechanical complications of MI or in patients with

pericardial tamponade. Transthoracic echocardiography is poorly

sensitive for aortic dissection, although an intimal flap may sometimes be detected in the ascending aorta.

MRI (See Chap. 241) Cardiac magnetic resonance (CMR) imaging

is an evolving, versatile technique for structural and functional

evaluation of the heart and the vasculature of the chest. CMR can be

performed as a modality for pharmacologic stress perfusion imaging. Gadolinium-enhanced CMR can provide early detection of MI,

defining areas of myocardial necrosis accurately, and can delineate

patterns of myocardial disease that are often useful in discriminating

ischemic from nonischemic myocardial injury. Although usually

not practical for the urgent evaluation of acute chest discomfort,

CMR can be a useful modality for cardiac structural evaluation of

patients with elevated cardiac troponin levels in the absence of definite coronary artery disease. CMR coronary angiography is in its

early stages. MRI also permits highly accurate assessment for aortic

dissection but is infrequently used as the first test because CT and

transesophageal echocardiography are usually more practical.

■ CRITICAL PATHWAYS FOR ACUTE CHEST

DISCOMFORT

Because of the challenges inherent in reliably identifying the small proportion of patients with serious causes of acute chest discomfort while

not exposing the larger number of low-risk patients to unnecessary

testing and extended ED or hospital evaluations, many medical centers

have adopted critical pathways to expedite the assessment and management of patients with nontraumatic chest pain, often in dedicated chest

pain units. Such pathways are generally aimed at (1) rapid identification, triage, and treatment of high-risk cardiopulmonary conditions

(e.g., STEMI); (2) accurate identification of low-risk patients who can

be safely observed in units with less intensive monitoring, undergo

early noninvasive testing, or be discharged home; and (3) through

more efficient and systematic accelerated diagnostic protocols, safe

reduction in costs associated with overuse of testing and unnecessary

hospitalizations. In some studies, provision of protocol-driven care in

chest pain units has decreased costs and overall duration of hospital

evaluation with no detectable excess of adverse clinical outcomes.

■ OUTPATIENT EVALUATION OF CHEST

DISCOMFORT

Chest pain is common in outpatient practice, with a lifetime prevalence of 20–40% in the general population. More than 25% of patients

with MI have had a related visit with a primary care physician in the

previous month. The diagnostic principles are the same as in the ED.

However, the pretest probability of an acute cardiopulmonary cause is

significantly lower. Therefore, testing paradigms are less intense, with

an emphasis on the history, physical examination, and ECG. Moreover,

decision-aids developed for settings with a high prevalence of significant cardiopulmonary disease have lower positive predictive value

when applied in the practitioner’s office. However, in general, if the

level of clinical suspicion of ACS is sufficiently high to consider troponin testing, the patient should be referred to the ED for evaluation.

■ FURTHER READING

Amsterdam EA et al: Testing of low-risk patients presenting to the

emergency department with chest pain: A scientific statement from

the American Heart Association. Circulation 122:1756, 2010.

Chapman AR et al: Association of high-sensitivity cardiac troponin I

concentration with cardiac outcomes in patients with suspected acute

coronary syndrome. JAMA 318:1913, 2017.

Fanaroff AC et al: Does this patient with chest pain have acute coronary syndrome? JAMA 314:1955, 2015.

Hsia RY et al: A national study of the prevalence of life-threatening

diagnoses in patients with chest pain. JAMA Intern Med 176:1029,

2016.

Mahler SA et al: Safely identifying emergency department patients

with acute chest pain for early discharge: HEART pathway accelerated diagnostic protocol. Circulation 138:2456, 2018.

Correctly diagnosing acute abdominal pain can be quite challenging.

Few clinical situations require greater judgment, because the most

catastrophic of events may be forecast by the subtlest of symptoms and

signs. In every instance, the clinician must distinguish those conditions

that require urgent intervention from those that do not and can best

be managed nonoperatively. A meticulously executed, detailed history

and physical examination are critically important for focusing the differential diagnosis and allowing the diagnostic evaluation to proceed

expeditiously (Table 15-1).

The etiologic classification in Table 15-2, although not complete,

provides a useful framework for evaluating patients with abdominal

pain.

Any patient with abdominal pain of recent onset requires an early

and thorough evaluation. The most common causes of abdominal pain

on admission are nonspecific abdominal pain, acute appendicitis, pain

of urologic origin, and intestinal obstruction. A diagnosis of “acute or

surgical abdomen” is not acceptable because of its often misleading

and erroneous connotations. Most patients who present with acute

abdominal pain will have self-limited disease processes. However,

it is important to remember that pain severity does not necessarily

correlate with the severity of the underlying condition. And, the presence or absence of various degrees of “hunger” is unreliable as a sole

indicator of the severity of intraabdominal disease. The most obvious

of “acute abdomens” may not require operative intervention, and the

mildest of abdominal pains may herald an urgently correctable disease.

■ SOME MECHANISMS OF PAIN ORIGINATING IN

THE ABDOMEN

Inflammation of the Parietal Peritoneum The pain of parietal peritoneal inflammation is steady and aching in character and is

located directly over the inflamed area, its exact reference being possible because it is transmitted by somatic nerves supplying the parietal

peritoneum. The intensity of the pain is dependent on the type and

amount of material to which the peritoneal surfaces are exposed in a

given time period. For example, the sudden release of a small quantity

15 Abdominal Pain

Danny O. Jacobs

TABLE 15-1 Some Key Components of the Patient’s History

Age

Time and mode of onset of the pain

Pain characteristics

Duration of symptoms

Location of pain and sites of radiation

Associated symptoms and their relationship to the pain

Nausea, emesis, and anorexia

Diarrhea, constipation, or other changes in bowel habits

Menstrual history

109Abdominal Pain CHAPTER 15

by palpation or by movement such as with coughing or sneezing. The

patient with peritonitis characteristically lies quietly in bed, preferring

to avoid motion, in contrast to the patient with colic, who may be

thrashing in discomfort.

Another characteristic feature of peritoneal irritation is tonic reflex

spasm of the abdominal musculature, localized to the involved body

segment. Its intensity depends on the integrity of the nervous system,

the location of the inflammatory process, and the rate at which it develops. Spasm over a perforated retrocecal appendix or perforation into

the lesser peritoneal sac may be minimal or absent because of the protective effect of overlying viscera. Catastrophic abdominal emergencies

may be associated with minimal or no detectable pain or muscle spasm

in obtunded, seriously ill, debilitated, immunosuppressed, or psychotic

patients. A slowly developing process also often greatly attenuates the

degree of muscle spasm.

Obstruction of Hollow Viscera Intraluminal obstruction classically elicits intermittent or colicky abdominal pain that is not as well

localized as the pain of parietal peritoneal irritation. However, the

absence of cramping discomfort can be misleading because distention of a hollow viscus may also produce steady pain with only rare

paroxysms.

Small-bowel obstruction often presents as poorly localized, intermittent periumbilical or supraumbilical pain. As the intestine progressively dilates and loses muscular tone, the colicky nature of the pain

may diminish. With superimposed strangulating obstruction, pain

may spread to the lower lumbar region if there is traction on the root

of the mesentery. The colicky pain of colonic obstruction is of lesser

intensity, is commonly located in the infraumbilical area, and may

often radiate to the lumbar region.

Sudden distention of the biliary tree produces a steady rather than

colicky type of pain; hence, the term biliary colic is misleading. Acute

distention of the gallbladder typically causes pain in the right upper

quadrant with radiation to the right posterior region of the thorax or

to the tip of the right scapula, but discomfort is also not uncommonly

found near the midline. Distention of the common bile duct often

causes epigastric pain that may radiate to the upper lumbar region.

Considerable variation is common, however, so that differentiation

between gallbladder or common ductal disease may be impossible.

Gradual dilatation of the biliary tree, as can occur with carcinoma of

the head of the pancreas, may cause no pain or only a mild aching sensation in the epigastrium or right upper quadrant. The pain of distention of the pancreatic ducts is similar to that described for distention of

the common bile duct but, in addition, is very frequently accentuated

by recumbency and relieved by the upright position.

Obstruction of the urinary bladder usually causes dull, low-intensity

pain in the suprapubic region. Restlessness, without specific complaint

of pain, may be the only sign of a distended bladder in an obtunded

patient. In contrast, acute obstruction of the intravesicular portion of the

ureter is characterized by severe suprapubic and flank pain that radiates

to the penis, scrotum, or inner aspect of the upper thigh. Obstruction

of the ureteropelvic junction manifests as pain near the costovertebral

angle, whereas obstruction of the remainder of the ureter is associated

with flank pain that often extends into the same side of the abdomen.

Vascular Disturbances A frequent misconception is that pain due

to intraabdominal vascular disturbances is sudden and catastrophic in

nature. Certain disease processes, such as embolism or thrombosis of

the superior mesenteric artery or impending rupture of an abdominal

aortic aneurysm, can certainly be associated with diffuse, severe pain.

Yet, just as frequently, the patient with occlusion of the superior mesenteric artery only has mild continuous or cramping diffuse pain for 2 or

3 days before vascular collapse or findings of peritoneal inflammation

appear. The early, seemingly insignificant discomfort is caused by

hyperperistalsis rather than peritoneal inflammation. Indeed, absence

of tenderness and rigidity in the presence of continuous, diffuse pain

(e.g., “pain out of proportion to physical findings”) in a patient likely to

have vascular disease is quite characteristic of occlusion of the superior

mesenteric artery. Abdominal pain with radiation to the sacral region,

TABLE 15-2 Some Important Causes of Abdominal Pain

Pain Originating in the Abdomen

Parietal peritoneal inflammation

Bacterial contamination

 Perforated appendix or other

perforated viscus

 Pelvic inflammatory disease

Chemical irritation

 Perforated ulcer

 Pancreatitis

 Mittelschmerz

Mechanical obstruction of hollow

viscera

 Obstruction of the small or large

intestine

Obstruction of the biliary tree

Obstruction of the ureter

Vascular disturbances

Embolism or thrombosis

Vascular rupture

Pressure or torsional occlusion

Sickle cell anemia

Abdominal wall

Distortion or traction of mesentery

Trauma or infection of muscles

Distension of visceral surfaces, e.g., by

hemorrhage

Hepatic or renal capsules

Inflammation

Appendicitis

Typhoid fever

 Neutropenic enterocolitis or

“typhlitis”

Pain Referred from Extraabdominal Source

Cardiothoracic

Acute myocardial infarction

 Myocarditis, endocarditis,

pericarditis

Congestive heart failure

Pneumonia (especially lower lobes)

Pulmonary embolus

Pleurodynia

Pneumothorax

Empyema

 Esophageal disease, including

spasm, rupture, or inflammation

Genitalia

Torsion of the testis

Metabolic Causes

Diabetes

Uremia

Hyperlipidemia

Hyperparathyroidism

Acute adrenal insufficiency

Familial Mediterranean fever

Porphyria

C1 esterase inhibitor deficiency

(angioneurotic edema)

Neurologic/Psychiatric Causes

Herpes zoster

Tabes dorsalis

Causalgia

Radiculitis from infection or arthritis

Spinal cord or nerve root compression

Functional disorders

Psychiatric disorders

Toxic Causes

Lead poisoning

Insect or animal envenomation

Black widow spider bites

Snake bites

Uncertain Mechanisms

Narcotic withdrawal

Heat stroke

of sterile acidic gastric juice into the peritoneal cavity causes much

more pain than the same amount of grossly contaminated neutral feces.

Enzymatically active pancreatic juice incites more pain and inflammation than does the same amount of sterile bile containing no potent

enzymes. Blood is normally only a mild irritant, and the response to

urine is also typically bland, so exposure of blood and urine to the

peritoneal cavity may go unnoticed unless it is sudden and massive.

Bacterial contamination, such as may occur with pelvic inflammatory

disease or perforated distal intestine, causes low-intensity pain until

multiplication causes significant amounts of inflammatory mediators

to be released. Patients with perforated upper gastrointestinal ulcers

may present entirely differently depending on how quickly gastric

juices enter the peritoneal cavity and their pH. Thus, the rate at which

any inflammatory material irritates the peritoneum is important.

The pain of peritoneal inflammation is invariably accentuated by

pressure or changes in tension of the peritoneum, whether produced

110 PART 2 Cardinal Manifestations and Presentation of Diseases

flank, or genitalia should always signal the possible presence of a rupturing abdominal aortic aneurysm. This pain may persist over a period

of several days before rupture and collapse occur.

Abdominal Wall Pain arising from the abdominal wall is usually

constant and aching. Movement, prolonged standing, and pressure

accentuate the discomfort and associated muscle spasm. In the relatively rare case of hematoma of the rectus sheath, now most frequently

encountered in association with anticoagulant therapy, a mass may be

present in the lower quadrants of the abdomen. Simultaneous involvement of muscles in other parts of the body usually serves to differentiate myositis of the abdominal wall from other processes that might

cause pain in the same region.

■ REFERRED PAIN IN ABDOMINAL DISEASE

Pain referred to the abdomen from the thorax, spine, or genitalia may

present a diagnostic challenge because diseases of the upper part of the

abdominal cavity such as acute cholecystitis or perforated ulcer may

be associated with intrathoracic complications. A most important, yet

often forgotten, dictum is that the possibility of intrathoracic disease

must be considered in every patient with abdominal pain, especially if

the pain is in the upper abdomen.

Systematic questioning and examination directed toward detecting myocardial or pulmonary infarction, pneumonia, pericarditis, or

esophageal disease (the intrathoracic diseases that most often masquerade as abdominal emergencies) will often provide sufficient clues

to establish the proper diagnosis. Diaphragmatic pleuritis resulting

from pneumonia or pulmonary infarction may cause pain in the right

upper quadrant and pain in the supraclavicular area, the latter radiation to be distinguished from the referred subscapular pain caused by

acute distention of the extrahepatic biliary tree. The ultimate decision

as to the origin of abdominal pain may require deliberate and planned

observation over a period of several hours, during which repeated

questioning and examination will provide the diagnosis or suggest the

appropriate studies.

Referred pain of thoracic origin is often accompanied by splinting

of the involved hemithorax with respiratory lag and a decrease in

excursion more marked than that seen in the presence of intraabdominal disease. In addition, apparent abdominal muscle spasm caused by

referred pain will diminish during the inspiratory phase of respiration,

whereas it persists throughout both respiratory phases if it is of abdominal origin. Palpation over the area of referred pain in the abdomen also

does not usually accentuate the pain and, in many instances, actually

seems to relieve it.

Thoracic disease and abdominal disease frequently coexist and may

be difficult or impossible to differentiate. For example, the patient with

known biliary tract disease often has epigastric pain during myocardial

infarction, or biliary colic may be referred to the precordium or left

shoulder in a patient who has suffered previously from angina pectoris.

For an explanation of the radiation of pain to a previously diseased

area, see Chap. 13.

Referred pain from the spine, which usually involves compression

or irritation of nerve roots, is characteristically intensified by certain motions such as cough, sneeze, or strain and is associated with

hyperesthesia over the involved dermatomes. Pain referred to the abdomen from the testes or seminal vesicles is generally accentuated by the

slightest pressure on either of these organs. The abdominal discomfort

experienced is of dull, aching character and is poorly localized.

■ METABOLIC ABDOMINAL CRISES

Pain of metabolic origin may simulate almost any other type of

intraabdominal disease. Several mechanisms may be at work. In certain instances, such as hyperlipidemia, the metabolic disease itself may

be accompanied by an intraabdominal process such as pancreatitis,

which can lead to unnecessary laparotomy unless recognized. C1

esterase deficiency associated with angioneurotic edema is often associated with episodes of severe abdominal pain. Whenever the cause of

abdominal pain is obscure, a metabolic origin always must be considered. Abdominal pain is also the hallmark of familial Mediterranean

fever (Chap. 369).

The pain of porphyria and of lead colic is usually difficult to distinguish from that of intestinal obstruction, because severe hyperperistalsis is a prominent feature of both. The pain of uremia or diabetes

is nonspecific, and the pain and tenderness frequently shift in location

and intensity. Diabetic acidosis may be precipitated by acute appendicitis or intestinal obstruction, so if prompt resolution of the abdominal

pain does not result from correction of the metabolic abnormalities, an

underlying organic problem should be suspected. Black widow spider

bites produce intense pain and rigidity of the abdominal muscles and

back, an area infrequently involved in intraabdominal disease.

■ IMMUNOCOMPROMISE

Evaluating and diagnosing causes of abdominal pain in immunosuppressed or otherwise immunocompromised patients is very difficult.

This includes those who have undergone organ transplantation; who

are receiving immunosuppressive treatments for autoimmune diseases, chemotherapy, or glucocorticoids; who have AIDS; and who

are very old. In these circumstances, normal physiologic responses

may be absent or masked. In addition, unusual infections may cause

abdominal pain where the etiologic agents include cytomegalovirus,

mycobacteria, protozoa, and fungi. These pathogens may affect all

gastrointestinal organs, including the gallbladder, liver, and pancreas,

as well as the gastrointestinal tract, causing occult or overtly symptomatic perforations of the latter. Splenic abscesses due to Candida or

Salmonella infection should also be considered, especially when evaluating patients with left upper quadrant or left flank pain. Acalculous

cholecystitis may be observed in immunocompromised patients or

those with AIDS, where it is often associated with cryptosporidiosis or

cytomegalovirus infection.

Neutropenic enterocolitis (typhlitis) is often identified as a cause

of abdominal pain and fever in some patients with bone marrow suppression due to chemotherapy. Acute graft-versus-host disease should

be considered in this circumstance. Optimal management of these

patients requires meticulous follow-up including serial examinations

to assess the need for more surgical intervention, for example, to

address perforation.

■ NEUROGENIC CAUSES

Diseases that injure sensory nerves may cause causalgic pain. This

pain has a burning character and is usually limited to the distribution

of a given peripheral nerve. Stimuli that are normally not painful such

as touch or a change in temperature may be causalgic and are often

present even at rest. The demonstration of irregularly spaced cutaneous

“pain spots” may be the only indication that an old nerve injury exists.

Even though the pain may be precipitated by gentle palpation, rigidity

of the abdominal muscles is absent, and the respirations are not usually

disturbed. Distention of the abdomen is uncommon, and the pain has

no relationship to food intake.

Pain arising from spinal nerves or roots comes and goes suddenly

and is of a lancinating type (Chap. 17). It may be caused by herpes

zoster, impingement by arthritis, tumors, a herniated nucleus pulposus,

diabetes, or syphilis. It is not associated with food intake, abdominal

distention, or changes in respiration. Severe muscle spasms, when present, may be relieved by, but are certainly not accentuated by, abdominal

palpation. The pain is made worse by movement of the spine and is

usually confined to a few dermatomes. Hyperesthesia is very common.

Pain due to functional causes conforms to none of the aforementioned patterns. Mechanisms of disease are not clearly established.

Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder

characterized by abdominal pain and altered bowel habits. The diagnosis is made on the basis of clinical criteria (Chap. 327) and after

exclusion of demonstrable structural abnormalities. The episodes of

abdominal pain may be brought on by stress, and the pain varies considerably in type and location. Nausea and vomiting are rare. Localized

111Abdominal Pain CHAPTER 15

TABLE 15-3 Differential Diagnoses of Abdominal Pain by Location

Right Upper Quadrant Epigastric Left Upper Quadrant

Cholecystitis

Cholangitis

Pancreatitis

Pneumonia/empyema

Pleurisy/pleurodynia

Subdiaphragmatic

abscess

Hepatitis

Budd-Chiari syndrome

Peptic ulcer disease

Gastritis

GERD

Pancreatitis

Myocardial infarction

Pericarditis

Ruptured aortic

aneurysm

Esophagitis

Splenic infarct

Splenic rupture

Splenic abscess

Gastritis

Gastric ulcer

Pancreatitis

Subdiaphragmatic

abscess

Right Lower Quadrant Periumbilical Left Lower Quadrant

Appendicitis

Salpingitis

Inguinal hernia

Ectopic pregnancy

Nephrolithiasis

Inflammatory bowel

disease

Mesenteric

lymphadenitis

Typhlitis

Early appendicitis

Gastroenteritis

Bowel obstruction

Ruptured aortic

aneurysm

Diverticulitis

Salpingitis

Inguinal hernia

Ectopic pregnancy

Nephrolithiasis

Irritable bowel syndrome

Inflammatory bowel

disease

Diffuse Nonlocalized Pain

Gastroenteritis

Mesenteric ischemia

Bowel obstruction

Irritable bowel syndrome

Peritonitis

Diabetes

Malaria

Familial Mediterranean

fever

Metabolic diseases

Psychiatric disease

Abbreviation: GERD, gastroesophageal reflux disease.

tenderness and muscle spasm are inconsistent or absent. The causes of

IBS or related functional disorders are not yet fully understood.

APPROACH TO THE PATIENT

Abdominal Pain

Few abdominal conditions require such urgent operative intervention that an orderly approach needs to be abandoned, no matter

how ill the patient is. Only patients with exsanguinating intraabdominal hemorrhage (e.g., ruptured aneurysm) must be rushed

to the operating room immediately, but in such instances, only a

few minutes are required to assess the critical nature of the problem. Under these circumstances, all obstacles must be swept aside,

adequate venous access for fluid replacement obtained, and the

operation begun. Unfortunately, many of these patients may die in

the radiology department or the emergency room while awaiting

unnecessary examinations. There are no absolute contraindications

to operation when massive intraabdominal hemorrhage is present.

Fortunately, this situation is relatively rare. This statement does

not necessarily apply to patients with intraluminal gastrointestinal

hemorrhage, who can often be managed by other means (Chap.

48). In these patients, obtaining a detailed history when possible

can be extremely helpful even though it can be laborious and timeconsuming. Decision-making regarding next steps is facilitated and

a reasonably accurate diagnosis can be made before any further

diagnostic testing is undertaken.

In cases of acute abdominal pain, a diagnosis can be readily

established in most instances, whereas success is not so frequent in

patients with chronic pain. IBS is one of the most common causes of

abdominal pain and must always be kept in mind (Chap. 327). The

location of the pain can assist in narrowing the differential diagnosis (Table 15-3); however, the chronological sequence of events in the

patient’s history is often more important than the pain’s location.

Careful attention should be paid to the extraabdominal regions.

Narcotics or analgesics should not be withheld until a definitive

diagnosis or a definitive plan has been formulated; obfuscation of

the diagnosis by adequate analgesia is unlikely.

An accurate menstrual history in a female patient is essential. It

is important to remember that normal anatomic relationships can

be significantly altered by the gravid uterus. Abdominal and pelvic

pain may occur during pregnancy due to conditions that do not

require operation. Lastly, some otherwise noteworthy laboratory

values (e.g., leukocytosis) may represent the normal physiologic

changes of pregnancy.

In the examination, simple critical inspection of the patient,

for example, of facies, position in bed, and respiratory activity,

provides valuable clues. The amount of information to be gleaned

is directly proportional to the gentleness and thoroughness of the

examiner. Once a patient with peritoneal inflammation has been

examined brusquely, accurate assessment by the next examiner

becomes almost impossible. Eliciting rebound tenderness by sudden release of a deeply palpating hand in a patient with suspected

peritonitis is cruel and unnecessary. The same information can

be obtained by gentle percussion of the abdomen (rebound tenderness on a miniature scale), a maneuver that can be far more

precise and localizing. Asking the patient to cough will elicit true

rebound tenderness without the need for placing a hand on the

abdomen. Furthermore, the forceful demonstration of rebound

tenderness will startle and induce protective spasm in a nervous or

worried patient in whom true rebound tenderness is not present. A

palpable gallbladder will be missed if palpation is so aggressive that

voluntary muscle spasm becomes superimposed on involuntary

muscular rigidity.

As with history taking, sufficient time should be spent in the

examination. Abdominal signs may be minimal but, nevertheless,

if accompanied by consistent symptoms, may be exceptionally

meaningful. Abdominal signs may be virtually or totally absent in

cases of pelvic peritonitis, so careful pelvic and rectal examinations

are mandatory in every patient with abdominal pain. Tenderness

on pelvic or rectal examination in the absence of other abdominal

signs can be caused by operative indications such as perforated

appendicitis, diverticulitis, twisted ovarian cyst, and many others.

Much attention has been paid to the presence or absence of peristaltic sounds, their quality, and their frequency. Auscultation of

the abdomen is one of the least revealing aspects of the physical

examination of a patient with abdominal pain. Catastrophes such

as a strangulating small-intestinal obstruction or perforated appendicitis may occur in the presence of normal peristaltic sounds. Conversely, when the proximal part of the intestine above obstruction

becomes markedly distended and edematous, peristaltic sounds

may lose the characteristics of borborygmi and become weak or

absent, even when peritonitis is not present. It is usually the severe

chemical peritonitis of sudden onset that is associated with the truly

silent abdomen.

Laboratory examinations may be valuable in assessing the patient

with abdominal pain, yet, with few exceptions, they rarely establish

a diagnosis. Leukocytosis should never be the single deciding factor as to whether or not operation is indicated. A white blood cell

count >20,000/μL may be observed with perforation of a viscus, but

pancreatitis, acute cholecystitis, pelvic inflammatory disease, and

intestinal infarction may also be associated with marked leukocytosis. A normal white blood cell count is not rare in cases of perforation of abdominal viscera. A diagnosis of anemia may be more

helpful than the white blood cell count, especially when combined

with the history.

The urinalysis may reveal the state of hydration or rule out severe

renal disease, diabetes, or urinary infection. Blood urea nitrogen,

glucose, and serum bilirubin levels and liver function tests may be

112 PART 2 Cardinal Manifestations and Presentation of Diseases

helpful. Serum amylase levels may be increased by many diseases

other than pancreatitis, for example, perforated ulcer, strangulating

intestinal obstruction, and acute cholecystitis; thus, elevations of

serum amylase do not rule in or rule out the need for an operation.

Plain and upright or lateral decubitus radiographs of the abdomen have limited utility and may be unnecessary in some patients

who have substantial evidence of some diseases such as acute

appendicitis or strangulated external hernia. Where the indications

for surgical or medical intervention are not clear, low-dose computed tomography is preferred to abdominal radiography when

evaluating nontraumatic acute abdominal pain.

Very rarely, barium or water-soluble contrast study of the upper

part of the gastrointestinal tract is an appropriate radiographic

investigation and may demonstrate partial intestinal obstruction

that may elude diagnosis by other means. If there is any question

of obstruction of the colon, oral administration of barium sulfate should be avoided. On the other hand, in cases of suspected

colonic obstruction (without perforation), a contrast enema may

be diagnostic.

In the absence of trauma, peritoneal lavage has been replaced as

a diagnostic tool by CT scanning and laparoscopy. Ultrasonography has proved to be useful in detecting an enlarged gallbladder or

pancreas, the presence of gallstones, an enlarged ovary, or a tubal

pregnancy. Laparoscopy is especially helpful in diagnosing pelvic

conditions, such as ovarian cysts, tubal pregnancies, salpingitis,

acute appendicitis, and other disease processes. Laparoscopy has a

particular advantage over imaging in that the underlying etiologic

condition can often be definitively addressed.

Radioisotopic hepatobiliary iminodiacetic acid scans (HIDAs)

may help differentiate acute cholecystitis or biliary colic from

acute pancreatitis. A CT scan may demonstrate an enlarged pancreas, ruptured spleen, or thickened colonic or appendiceal wall

and streaking of the mesocolon or mesoappendix characteristic of

diverticulitis or appendicitis.

Sometimes, even under the best circumstances with all available

aids and with the greatest of clinical skill, a definitive diagnosis

cannot be established at the time of the initial examination. And, in

some cases, operation may be indicated based on clinical grounds

alone. Should that decision be questionable, watchful waiting with

repeated questioning and examination will often elucidate the true

nature of the illness and indicate the proper course of action.

Acknowledgment

The author gratefully acknowledges the enormous contribution to this

chapter and the approach it espouses of William Silen, who wrote this

chapter for many editions.

■ FURTHER READING

Bhangu A et al: Acute appendicitis: Modern understanding of pathogenesis, diagnosis and management. Lancet 386:1278, 2015.

Cartwright SL, Knudson MP: Diagnostic imaging of acute abdominal pain in adults. Am Fam Phys 91:452, 2015.

Huckins DS et al: Diagnostic performance of a biomarker panel as a

negative predictor for acute appendicitis in acute emergency department patients with abdominal pain. Am J Emerg Med 35:418, 2017.

Nayor J et al: Tracing the cause of abdominal pain. N Engl J Med

375:e8, 2016.

Phillips MT: Clinical yield of computed tomography scans in the

emergency department for abdominal pain. J Invest Med 64:542,

2016.

Silen W, Cope Z: Cope’s Early Diagnosis of the Acute Abdomen, 22nd ed.

New York, Oxford University Press, 2010.

Headache is among the most common reasons patients seek medical

attention and is responsible, on a global basis, for more disability than

any other neurologic problem. Diagnosis and management are based

on a careful clinical approach augmented by an understanding of the

anatomy, physiology, and pharmacology of the nervous system pathways mediating the various headache syndromes. This chapter will

focus on the general approach to a patient with headache; migraine and

other primary headache disorders are discussed in Chap. 430.

■ GENERAL PRINCIPLES

A classification system developed by the International Headache

Society (www.ihs-headache.org/en/resources/guidelines/) characterizes

headache as primary or secondary (Table 16-1). Primary headaches

are those in which headache and its associated features are the disorder

itself, whereas secondary headaches are those caused by exogenous disorders (Headache Classification Committee of the International Headache Society, 2018). Primary headache often results in considerable

disability and a decrease in the patient’s quality of life. Mild secondary

headache, such as that seen in association with upper respiratory tract

infections, is common but rarely worrisome. Life-threatening headache

is relatively uncommon, but vigilance is required in order to recognize

and appropriately treat such patients.

■ ANATOMY AND PHYSIOLOGY OF HEADACHE

Pain usually occurs when peripheral nociceptors are stimulated in

response to tissue injury, visceral distension, or other factors (Chap. 13).

In such situations, pain perception is a normal physiologic response

mediated by a healthy nervous system. Pain can also result when

pain-producing pathways of the peripheral or central nervous system

(CNS) are damaged or activated inappropriately. Headache may originate from either or both mechanisms. Relatively few cranial structures

are pain producing; these include the scalp, meningeal arteries, dural

sinuses, falx cerebri, and proximal segments of the large pial arteries.

The ventricular ependyma, choroid plexus, pial veins, and much of the

brain parenchyma are not pain producing.

The key structures involved in primary headache are the following:

• The large intracranial vessels and dura mater, and the peripheral

terminals of the trigeminal nerve that innervate these structures

• The caudal portion of the trigeminal nucleus, which extends into

the dorsal horns of the upper cervical spinal cord and receives input

from the first and second cervical nerve roots (the trigeminocervical

complex)

• Rostral pain-processing regions, such as the ventroposteromedial

thalamus and the cortex

• The pain-modulatory systems in the brain that modulate input from

the trigeminal nociceptors at all levels of the pain-processing pathways and influence vegetative functions, such as the hypothalamus

and brainstem

16 Headache

Peter J. Goadsby

TABLE 16-1 Common Causes of Headache

PRIMARY HEADACHE SECONDARY HEADACHE

TYPE % TYPE %

Tension-type 69 Systemic infection 63

Migraine 16 Head injury 4

Idiopathic stabbing 2 Vascular disorders 1

Exertional 1 Subarachnoid hemorrhage <1

Cluster 0.1 Brain tumor 0.1

Source: After J Olesen et al: The Headaches. Philadelphia, Lippincott Williams &

Wilkins, 2005.

113Headache CHAPTER 16

The trigeminovascular system innervates the large intracranial

vessels and dura mater via the trigeminal nerve. Cranial autonomic

symptoms, such as lacrimation, conjunctival injection, nasal congestion, rhinorrhea, periorbital swelling, aural fullness, and ptosis,

are prominent in the trigeminal autonomic cephalalgias (TACs),

including cluster headache and paroxysmal hemicrania, and may also

be seen in migraine, even in children. These autonomic symptoms

reflect activation of cranial parasympathetic pathways, and functional

imaging studies indicate that vascular changes in migraine and cluster

headache, when present, are similarly driven by these cranial autonomic systems. Thus, they are secondary, and not causative, events

in the headache cascade. Moreover, they can often be mistaken for

symptoms or signs of cranial sinus inflammation, which is then overdiagnosed and inappropriately managed. Migraine and other primary

headache types are not “vascular headaches”; these disorders do not

reliably manifest vascular changes, and treatment outcomes cannot be

predicted by vascular effects. Migraine is a brain disorder and is best

understood and managed as such.

■ CLINICAL EVALUATION OF ACUTE,

NEW-ONSET HEADACHE

The patient who presents with a new, severe headache has a differential diagnosis that is quite different from the patient with recurrent

headaches over many years. In new-onset and severe headache, the

probability of finding a potentially serious cause is considerably greater

than in recurrent headache. Patients with recent onset of pain require

prompt evaluation and appropriate treatment. Serious causes to be

considered include meningitis, subarachnoid hemorrhage, epidural or

subdural hematoma, glaucoma, tumor, and purulent sinusitis. When

worrisome symptoms and signs are present (Table 16-2), rapid diagnosis and management are critical.

A careful neurologic examination is an essential first step in the

evaluation. In most cases, patients with an abnormal examination or

a history of recent-onset headache should be evaluated by a computed

tomography (CT) or magnetic resonance imaging (MRI) study of the

brain. As an initial screening procedure for intracranial pathology in

this setting, CT and MRI methods appear to be equally sensitive. In

some circumstances, a lumbar puncture (LP) is also required, unless

a benign etiology can be otherwise established. A general evaluation

of acute headache might include cranial arteries by palpation; cervical

spine by the effect of passive movement of the head and by imaging;

the investigation of cardiovascular and renal status by blood pressure

monitoring and urine examination; and eyes by funduscopy, intraocular pressure measurement, and refraction.

The patient’s psychological state should also be evaluated because a

relationship exists between head pain, depression, and anxiety. This is

intended to identify comorbidity rather than provide an explanation

for the headache, because troublesome headache is seldom simply

caused by mood change. Although it is notable that medicines with

antidepressant actions are also effective in the preventive treatment

TABLE 16-2 Headache Symptoms That Suggest a Serious Underlying

Disorder

Sudden-onset headache

First severe headache

“Worst” headache ever

Vomiting that precedes headache

Subacute worsening over days or weeks

Pain induced by bending, lifting, coughing

Pain that disturbs sleep or presents immediately upon awakening

Known systemic illness

Onset after age 55

Fever or unexplained systemic signs

Abnormal neurologic examination

Pain associated with local tenderness, e.g., region of temporal artery

of both tension-type headache and migraine, each symptom must be

treated optimally.

Underlying recurrent headache disorders may be activated by pain

that follows otologic or endodontic surgical procedures. Thus, pain

about the head as the result of diseased tissue or trauma may reawaken

an otherwise quiescent migraine syndrome. Treatment of the headache is largely ineffective until the cause of the primary problem is

addressed.

Serious underlying conditions that are associated with headache are

described below. Brain tumor is a rare cause of headache and even less

commonly a cause of severe pain. The vast majority of patients presenting with severe headache have a benign cause.

SECONDARY HEADACHE

The management of secondary headache focuses on diagnosis and

treatment of the underlying condition.

■ MENINGITIS

Acute, severe headache with stiff neck and fever suggests meningitis.

LP is mandatory. Often there is striking accentuation of pain with eye

movement. Meningitis can be easily mistaken for migraine in that the

cardinal symptoms of pounding headache, photophobia, nausea, and

vomiting are frequently present, perhaps reflecting the underlying

biology of some of the patients.

Meningitis is discussed in Chaps. 138 and 139.

■ INTRACRANIAL HEMORRHAGE

Acute, maximal in <5 min, severe headache lasting >5 min with stiff

neck but without fever suggests subarachnoid hemorrhage. A ruptured

aneurysm, arteriovenous malformation, or intraparenchymal hemorrhage may also present with headache alone. Rarely, if the hemorrhage

is small or below the foramen magnum, the head CT scan can be

normal. Therefore, LP may be required to diagnose definitively subarachnoid hemorrhage.

Subarachnoid hemorrhage is discussed in Chap. 429, and intracranial hemorrhage in Chap. 428.

■ BRAIN TUMOR

Approximately 30% of patients with brain tumors consider headache

to be their chief complaint. The head pain is usually nondescript—an

intermittent deep, dull aching of moderate intensity, which may worsen

with exertion or change in position and may be associated with nausea

and vomiting. This pattern of symptoms results from migraine far more

often than from brain tumor. The headache of brain tumor disturbs

sleep in about 10% of patients. Vomiting that precedes the appearance

of headache by weeks is highly characteristic of posterior fossa brain

tumors. A history of amenorrhea or galactorrhea should lead one to

question whether a prolactin-secreting pituitary adenoma (or polycystic

ovary syndrome) is the source of headache. Headache arising de novo in

a patient with known malignancy suggests either cerebral metastases or

carcinomatous meningitis. Head pain appearing abruptly after bending,

lifting, or coughing can be due to a posterior fossa mass, a Chiari malformation, or low cerebrospinal fluid (CSF) volume.

Brain tumors are discussed in Chap. 90.

■ TEMPORAL ARTERITIS (SEE ALSO CHAPS. 32 AND 363)

Temporal (giant cell) arteritis is an inflammatory disorder of arteries

that frequently involves the extracranial carotid circulation. It is a

common disorder of the elderly; its annual incidence is 77 per 100,000

individuals aged ≥50. The average age of onset is 70 years, and women

account for 65% of cases. About half of patients with untreated temporal arteritis develop blindness due to involvement of the ophthalmic

artery and its branches; indeed, the ischemic optic neuropathy induced

by giant cell arteritis is the major cause of rapidly developing bilateral

blindness in patients >60 years. Because treatment with glucocorticoids

is effective in preventing this complication, prompt recognition of the

disorder is important.

Typical presenting symptoms include headache, polymyalgia rheumatica (Chap. 363), jaw claudication, fever, and weight loss. Headache

 

99Pain: Pathophysiology and Management CHAPTER 13

typically lasting just hours after the cessation of the infusion. The

oral lidocaine congener mexiletine is poorly tolerated, producing

frequent gastrointestinal adverse effects. There is no consensus on

which class of drug should be used as a first-line treatment for any

chronically painful condition. However, because relatively high

doses of anticonvulsants are required for pain relief, sedation is not

uncommon. Sedation is also a problem with TCAs but is much less

of a problem with serotonin/norepinephrine reuptake inhibitors

(SNRIs; e.g., venlafaxine and duloxetine). Thus, in the elderly or

in patients whose daily activities require high-level mental activity,

these drugs should be considered the first line. In contrast, opioid

medications should be used as a second- or third-line drug class.

Although highly effective for many painful conditions, opioids are

sedating, and their effect tends to lessen over time, leading to dose

escalation and, occasionally, a worsening of pain. A couple of interesting alternatives to pure opioids are two drugs with mixed opioid

and norepinephrine reuptake action: tramadol and tapentadol.

Tramadol is a relatively weak opioid but is sometimes effective for

pain unresponsive to nonopioid analgesics. Tapentadol is a stronger

opioid, but its analgesic action is apparently enhanced by the norepinephrine reuptake blockade. Similarly, drugs of different classes

can be used in combination to optimize pain control. Repeated

injection of botulinum toxin is an emerging approach that is showing some promise in treating focal neuropathic pain, particularly

post-herpetic, trigeminal, and post-traumatic neuralgias.

It is worth emphasizing that many patients, especially those with

chronic pain, seek medical attention primarily because they are

suffering and because only physicians can provide the medications

required for pain relief. A primary responsibility of all physicians

is to minimize the physical and emotional discomfort of their

patients. Familiarity with pain mechanisms and analgesic medications is an important step toward accomplishing this aim.

■ FURTHER READING

De Vita MJ et al: Association of cannabinoid administration with

experimental pain in healthy adults a systematic review and

meta-analysis. JAMA Psychiatry 75:1118, 2018.

Dowell D et al: CDC guideline for prescribing opioids for chronic

pain—United States, 2016. JAMA 315:1624, 2016.

Finnerup NB et al: Pharmacotherapy for neuropathic pain in adults:

A systematic review and meta-analysis. Lancet Neurol 14:162, 2015.

Sun EC et al: Incidence of and risk factors for chronic opioid use

among opioid-naive patients in the postoperative period. JAMA

Intern Med 176:1286, 2016.

U.S. Department of Health and Human Services: Pain management best practices inter-agency task force report: Updates, gaps,

inconsistencies, and recommendations. May 2019. https://www.hhs.

gov/ash/advisory-committees/pain/reports/index.html.

TABLE 13-3 Guidelines for Selecting and Monitoring Patients

Receiving Chronic Opioid Therapy (COT) for the Treatment of

Chronic, Noncancer Pain

Patient Selection

• Conduct a history, physical examination, and appropriate testing, including an

assessment of risk of substance abuse, misuse, or addiction.

• Consider a trial of COT if pain is moderate or severe, pain is having an adverse

impact on function or quality of life, and potential therapeutic benefits

outweigh potential harms.

• A benefit-to-harm evaluation, including a history, physical examination, and

appropriate diagnostic testing, should be performed and documented before

and on an ongoing basis during COT.

Informed Consent and Use of Management Plans

• Informed consent should be obtained. A continuing discussion with the

patient regarding COT should include goals, expectations, potential risks, and

alternatives to COT.

• Consider using a written COT management plan to document patient and

clinician responsibilities and expectations and assist in patient education.

Initiation and Titration

• Initial treatment with opioids should be considered as a therapeutic trial to

determine whether COT is appropriate.

• Opioid selection, initial dosing, and titration should be individualized according

to the patient’s health status, previous exposure to opioids, attainment of

therapeutic goals, and predicted or observed harms.

Monitoring

• Reassess patients on COT periodically and as warranted by changing

circumstances. Monitoring should include documentation of pain intensity and

level of functioning, assessments of progress toward achieving therapeutic

goals, presence of adverse events, and adherence to prescribed therapies.

• In patients on COT who are at high risk or who have engaged in aberrant drugrelated behaviors, clinicians should periodically obtain urine drug screens or

other information to confirm adherence to the COT plan of care.

• In patients on COT not at high risk and not known to have engaged in aberrant

drug-related behaviors, clinicians should consider periodically obtaining urine

drug screens or other information to confirm adherence to the COT plan of

care.

Source: Adapted with permission from R Chou et al: Clinical guidelines for the use

of chronic opioid therapy in chronic noncancer pain. J Pain 10:113, 2009.

TABLE 13-4 Centers for Disease Control and Prevention Checklist for

Prescribing Opioids for Chronic Pain

For Primary Care Providers Treating Adults (18+) with Chronic Pain

≥3 months, Excluding Cancer, Palliative, and End-of-Life Care

CHECKLIST

WHEN CONSIDERING LONG-TERM OPIOID THERAPY

• Set realistic goals for pain and function based on diagnosis (e.g., walk around

the block).

• Check that nonopioid therapies tried and optimized.

• Discuss benefits and risks (e.g., addiction, overdose) with patient.

• Evaluate risk of harm or misuse.

• Discuss risk factors with patient.

• Check prescription drug monitoring program (PDMP) data.

• Check urine drug screen.

• Set criteria for stopping or continuing opioids.

• Assess baseline pain and function (e.g., Pain, Enjoyment, General Activity

[PEG] scale).

• Schedule initial reassessment within 1–4 weeks.

• Prescribe short-acting opioids using lowest dosage on product labeling;

match duration to scheduled reassessment.

IF RENEWING WITHOUT A PATIENT VISIT

• Check that return visit is scheduled ≤3 months from last visit.

WHEN REASSESSING AT A PATIENT VISIT

• Continue opioids only after confirming clinically meaningful improvements in

pain and function without significant risks or harm.

• Assess pain and function (e.g., PEG); compare results to baseline.

• Evaluate risk of harm or misuse:

• Observe patient for signs of oversedation or overdose risk. If yes: Taper

dose.

• Check PDMP.

• Check for opioid use disorder if indicated (e.g., difficulty controlling use). If

yes: Refer for treatment.

• Check that nonopioid therapies optimized. Determine whether to continue,

adjust, taper, or stop opioids.

• Calculate opioid dosage morphine milligram equivalent (MME).

• If ≥50 MME/day total (≥50 mg hydrocodone; ≥33 mg oxycodone), increase

frequency of follow-up; consider offering naloxone.

• Avoid ≥90 MME/day total (≥90 mg hydrocodone; ≥60 mg oxycodone), or

carefully justify; consider specialist referral.

• Schedule reassessment at regular intervals (≤3 months).

Source: Centers for Disease Control and Prevention, available at: https://stacks.cdc.

gov/view/cdc/38025. Accessed May 25, 2017 (Public Domain).

100 PART 2 Cardinal Manifestations and Presentation of Diseases

Chest discomfort is among the most common reasons for which

patients present for medical attention at either an emergency department (ED) or an outpatient clinic. The evaluation of nontraumatic

chest discomfort is inherently challenging owing to the broad variety

of possible causes, a minority of which are life-threatening conditions

that should not be missed. It is helpful to frame the initial diagnostic

assessment and triage of patients with acute chest discomfort around

three categories: (1) myocardial ischemia; (2) other cardiopulmonary

causes (myopericardial disease, aortic emergencies, and pulmonary

conditions); and (3) noncardiopulmonary causes. Although rapid

identification of high-risk conditions is a priority of the initial assessment, strategies that incorporate routine liberal use of testing carry the

potential for adverse effects of unnecessary investigations.

EPIDEMIOLOGY AND NATURAL HISTORY

Chest discomfort is one of the three most common reason for visits to

the ED in the United States, resulting in 6 to 7 million emergency visits

each year. More than 60% of patients with this presentation are hospitalized for further testing, and most of the remainder undergo additional investigation in the ED. Fewer than 15% of evaluated patients are

eventually diagnosed with acute coronary syndrome (ACS), with rates

of 10–20% in most series of unselected populations, and a rate as low as

5% in some studies. The most common diagnoses are gastrointestinal

causes (Fig. 14-1), and as few as 5% are other life-threatening cardiopulmonary conditions. In a large proportion of patients with transient

acute chest discomfort, ACS or another acute cardiopulmonary cause is

excluded but the cause is not determined. Therefore, the resources and

time devoted to the evaluation of chest discomfort in the absence of a

severe cause are substantial. Nevertheless, historically, a disconcerting

2–6% of patients with chest discomfort of presumed nonischemic etiology who are discharged from the ED were later deemed to have had a

missed myocardial infarction (MI). Patients with a missed diagnosis of

MI have a 30-day risk of death that is double that of their counterparts

who are hospitalized.

The natural histories of ACS, myocarditis, acute pericardial diseases, pulmonary embolism, and aortic emergencies are discussed in

Chaps. 270, 273, 274, 275, 279, and 280, respectively. In a study of more

than 350,000 patients with unspecified presumed noncardiopulmonary

chest discomfort, the mortality rate 1 year after discharge was <2% and

did not differ significantly from age-adjusted mortality in the general

14 Chest Discomfort

David A. Morrow

population. The estimated rate of major cardiovascular events through

30 days in patients with acute chest pain who had been stratified as low

risk was 2.5% in a large population-based study that excluded patients

with ST-segment elevation or definite noncardiac chest pain.

CAUSES OF CHEST DISCOMFORT

The major etiologies of chest discomfort are discussed in this section

and summarized in Table 14-1. Additional elements of the history,

physical examination, and diagnostic testing that aid in distinguishing these causes are discussed in a later section (see “Approach to the

Patient”).

■ MYOCARDIAL ISCHEMIA/INJURY

Myocardial ischemia causing chest discomfort, termed angina pectoris, is a primary clinical concern in patients presenting with chest

symptoms. Myocardial ischemia is precipitated by an imbalance

between myocardial oxygen requirements and myocardial oxygen

supply, resulting in insufficient delivery of oxygen to meet the heart’s

metabolic demands. Myocardial oxygen consumption may be elevated

by increases in heart rate, ventricular wall stress, and myocardial contractility, whereas myocardial oxygen supply is determined by coronary

blood flow and coronary arterial oxygen content. When myocardial

ischemia is sufficiently severe and prolonged in duration (as little as

20 min), irreversible cellular injury occurs, resulting in MI.

Ischemic heart disease is most commonly caused by atheromatous

plaque that obstructs one or more of the epicardial coronary arteries.

Stable ischemic heart disease (Chap. 273) usually results from the

gradual atherosclerotic narrowing of the coronary arteries. Stable

angina is characterized by ischemic episodes that are typically precipitated by a superimposed increase in oxygen demand during physical

exertion and relieved upon resting. Ischemic heart disease becomes

unstable, manifest by ischemia at rest or with an escalating pattern,

most commonly when rupture or erosion of one or more atherosclerotic lesions triggers coronary thrombosis. Unstable ischemic heart

disease is further classified clinically by the presence or absence of

detectable acute myocardial injury and the presence or absence of

ST-segment elevation on the patient’s electrocardiogram (ECG). When

acute coronary atherothrombosis occurs, the intracoronary thrombus

may be partially obstructive, generally leading to myocardial ischemia

in the absence of ST-segment elevation. Unstable ischemic heart disease is classified as unstable angina when there is no detectable acute

myocardial injury and as non–ST elevation MI (NSTEMI) when there is

evidence of acute myocardial necrosis (Chap. 274). When the coronary

thrombus is acutely and completely occlusive, transmural myocardial

ischemia usually ensues, with ST-segment elevation on the ECG and

myocardial necrosis leading to a diagnosis of ST elevation MI (STEMI;

see Chap. 275).

Gastrointestinal 42%

Ischemic heart disease 31%

Chest wall syndrome 28%

Pericarditis 4%

Pleuritis 2%

Pulmonary embolism 2%

Lung cancer 1.5%

Aortic aneurysm 1%

Aortic stenosis 1%

Herpes zoster 1%

FIGURE 14-1 Distribution of final discharge diagnoses in patients with nontraumatic acute chest pain. (Figure prepared from data in P Fruergaard et al: Eur Heart J 17:1028,

1996.)

101Chest Discomfort CHAPTER 14

TABLE 14-1 Typical Clinical Features of Major Causes of Acute Chest Discomfort

SYSTEM CONDITION ONSET/DURATION QUALITY LOCATION ASSOCIATED FEATURES

Cardiopulmonary

Cardiac Myocardial ischemia Stable angina:

Precipitated by exertion,

cold, or stress; 2–10 min

Unstable angina:

Increasing pattern or

at rest

Myocardial infarction:

Usually >30 min

Pressure, tightness,

squeezing, heaviness,

burning

Retrosternal; often

radiation to neck, jaw,

shoulders, or arms;

sometimes epigastric

S4

 gallop or mitral regurgitation

murmur (rare) during pain; S3

or rales if severe ischemia or

complication of myocardial

infarction

Pericarditis Variable; hours to days;

may be episodic

Pleuritic, sharp Retrosternal or toward

cardiac apex; may radiate

to left shoulder

May be relieved by sitting up

and leaning forward; pericardial

friction rub

Vascular Acute aortic syndrome Sudden onset of

unrelenting pain

Tearing or ripping;

knifelike

Anterior chest, often

radiating to back,

between shoulder blades

Associated with hypertension

and/or underlying connective

tissue disorder; murmur of aortic

insufficiency; loss of peripheral

pulses

Pulmonary embolism Sudden onset Pleuritic; may manifest as

heaviness with massive

pulmonary embolism

Often lateral, on the side

of the embolism

Dyspnea, tachypnea, tachycardia,

and hypotension

Pulmonary hypertension Variable; often exertional Pressure Substernal Dyspnea, signs of increased

venous pressure

Pulmonary Pneumonia or pleuritis Variable Pleuritic Unilateral, often localized Dyspnea, cough, fever, rales,

occasional rub

Spontaneous

pneumothorax

Sudden onset Pleuritic Lateral to side of

pneumothorax

Dyspnea, decreased breath

sounds on side of pneumothorax

Noncardiopulmonary

Gastrointestinal Esophageal reflux 10–60 min Burning Substernal, epigastric Worsened by postprandial

recumbency; relieved by antacids

Esophageal spasm 2–30 min Pressure, tightness,

burning

Retrosternal Can closely mimic angina

Peptic ulcer Prolonged; 60–90 min

after meals

Burning Epigastric, substernal Relieved with food or antacids

Gallbladder disease Prolonged Aching or colicky Epigastric, right upper

quadrant; sometimes to

the back

May follow meal

Neuromuscular Costochondritis Variable Aching Sternal Sometimes swollen, tender, warm

over joint; may be reproduced

by localized pressure on

examination

Cervical disk disease Variable; may be sudden Aching; may include

numbness

Arms and shoulders May be exacerbated by

movement of neck

Trauma or strain Usually constant Aching Localized to area of strain Reproduced by movement or

palpation

Herpes zoster Usually prolonged Sharp or burning Dermatomal distribution Vesicular rash in area of

discomfort

Psychological Emotional and psychiatric

conditions

Variable; may be fleeting

or prolonged

Variable; often manifests

as tightness and dyspnea

with feeling of panic or

doom

Variable; may be

retrosternal

Situational factors may

precipitate symptoms; history of

panic attacks, depression

Clinicians should be aware that unstable ischemic symptoms may

also occur predominantly because of increased myocardial oxygen

demand (e.g., during intense psychological stress or fever) or because

of decreased oxygen delivery due to anemia, hypoxia, or hypotension.

However, the term acute coronary syndrome, which encompasses unstable angina, NSTEMI, and STEMI, is in general reserved for ischemia

precipitated by acute coronary atherothrombosis. In order to guide therapeutic strategies, a standardized system for classification of MI has been

expanded to discriminate MI resulting from acute coronary thrombosis

(type 1 MI) from MI occurring secondary to other imbalances of myocardial oxygen supply and demand (type 2 MI; see Chap. 274). These

conditions are additionally distinguished from nonischemic causes of

acute myocardial injury, such as myocarditis.

Other contributors to stable and unstable ischemic heart disease,

such as endothelial dysfunction, microvascular disease, and vasospasm, may exist alone or in combination with coronary atherosclerosis and may be the dominant cause of myocardial ischemia in some

patients. Moreover, nonatherosclerotic processes, including congenital

abnormalities of the coronary vessels, myocardial bridging, coronary

arteritis, and radiation-induced coronary disease, can lead to coronary

obstruction. In addition, conditions associated with extreme myocardial oxygen demand and impaired endocardial blood flow, such

as aortic valve disease (Chap. 280), hypertrophic cardiomyopathy, or

idiopathic dilated cardiomyopathy (Chap. 259), can precipitate myocardial ischemia in patients with or without underlying obstructive

atherosclerosis.

102 PART 2 Cardinal Manifestations and Presentation of Diseases

Characteristics of Ischemic Chest Discomfort The clinical

characteristics of angina pectoris, often referred to simply as “angina,”

are highly similar whether the ischemic discomfort is a manifestation

of stable ischemic heart disease, unstable angina, or MI; the exceptions

are differences in the pattern and duration of symptoms associated

with these syndromes (Table 14-1). Heberden initially described

angina as a sense of “strangling and anxiety.” Chest discomfort characteristic of myocardial ischemia is typically described as aching, heavy,

squeezing, crushing, or constricting. However, in a substantial minority of patients, the quality of discomfort is extremely vague and may be

described as a mild tightness, or merely an uncomfortable feeling, that

sometimes is experienced as numbness or a burning sensation. The

site of the discomfort is usually retrosternal, but radiation is common

and generally occurs down the ulnar surface of the left arm; the right

arm, both arms, neck, jaw, or shoulders may also be involved. These

and other characteristics of ischemic chest discomfort pertinent to

discrimination from other causes of chest pain are discussed later in

this chapter (see “Approach to the Patient”).

Stable angina usually begins gradually and reaches its maximal

intensity over a period of minutes before dissipating within several

minutes with rest or with nitroglycerin. The discomfort typically

occurs predictably at a characteristic level of exertion or psychological stress. By definition, unstable angina is manifest by anginal chest

discomfort that occurs with progressively lower intensity of physical

activity or even at rest. Chest discomfort associated with MI is commonly more severe, is prolonged (usually lasting ≥30 min), and is not

relieved by rest.

Mechanisms of Cardiac Pain The neural pathways involved in

ischemic cardiac pain are poorly understood. Ischemic episodes are

thought to excite local chemosensitive and mechanoreceptive receptors

that, in turn, stimulate release of adenosine, bradykinin, and other substances that activate the sensory ends of sympathetic and vagal afferent

fibers. The afferent fibers traverse the nerves that connect to the upper

five thoracic sympathetic ganglia and upper five distal thoracic roots of

the spinal cord. From there, impulses are transmitted to the thalamus.

Within the spinal cord, cardiac sympathetic afferent impulses may

converge with impulses from somatic thoracic structures, and this

convergence may be the basis for referred cardiac pain. In addition,

cardiac vagal afferent fibers synapse in the nucleus tractus solitarius

of the medulla and then descend to the upper cervical spinothalamic

tract, and this route may contribute to anginal pain experienced in the

neck and jaw.

■ OTHER CARDIOPULMONARY CAUSES

Pericardial and Other Myocardial Diseases (See also Chap. 270)

Inflammation of the pericardium due to infectious or noninfectious

causes can be responsible for acute or chronic chest discomfort. The

visceral surface and most of the parietal surface of the pericardium

are insensitive to pain. Therefore, the pain of pericarditis is thought

to arise principally from associated pleural inflammation. Because

of this pleural association, the discomfort of pericarditis is usually

pleuritic pain that is exacerbated by breathing, coughing, or changes

in position. Moreover, owing to the overlapping sensory supply of the

central diaphragm via the phrenic nerve with somatic sensory fibers

originating in the third to fifth cervical segments, the pain of pleural

and pericardial inflammation is often referred to the shoulder and

neck. Involvement of the pleural surface of the lateral diaphragm can

lead to pain in the upper abdomen.

Acute inflammatory and other nonischemic myocardial diseases

can also produce chest discomfort. The symptoms of acute myocarditis are highly varied. Chest discomfort may either originate with

inflammatory injury of the myocardium or be due to severe increases

in wall stress related to poor ventricular performance. The symptoms

of Takotsubo (stress-related) cardiomyopathy often start abruptly with

chest pain and shortness of breath. This form of cardiomyopathy, in its

most recognizable form, is triggered by an emotionally or physically

stressful event and may mimic acute MI because of its commonly

associated ECG abnormalities, including ST-segment elevation, and

elevated biomarkers of myocardial injury. Observational studies support a predilection for women >50 years of age.

Diseases of the Aorta (See also Chap. 280) Acute aortic dissection (Fig. 14-1) is a less common cause of chest discomfort but is

important because of the catastrophic natural history of certain subsets

of cases when recognized late or left untreated. Acute aortic syndromes

encompass a spectrum of acute aortic diseases related to disruption

of the media of the aortic wall. Aortic dissection involves a tear in the

aortic intima, resulting in separation of the media and creation of a

separate “false” lumen. A penetrating ulcer has been described as ulceration of an aortic atheromatous plaque that extends through the intima

and into the aortic media, with the potential to initiate an intramedial

dissection or rupture into the adventitia. Intramural hematoma is an

aortic wall hematoma with no demonstrable intimal flap, no radiologically apparent intimal tear, and no false lumen. Intramural hematoma

can occur due to either rupture of the vasa vasorum or, less commonly,

a penetrating ulcer.

Each of these subtypes of acute aortic syndrome typically presents

with chest discomfort that is often severe, sudden in onset, and

sometimes described as “tearing” in quality. Acute aortic syndromes

involving the ascending aorta tend to cause pain in the midline of

the anterior chest, whereas descending aortic syndromes most often

present with pain in the back. Therefore, dissections that begin in the

ascending aorta and extend to the descending aorta tend to cause pain

in the front of the chest that extends toward the back, between the

shoulder blades. Proximal aortic dissections that involve the ascending

aorta (type A in the Stanford nomenclature) are at high risk for major

complications that may influence the clinical presentation, including

(1) compromise of the aortic ostia of the coronary arteries, resulting

in MI; (2) disruption of the aortic valve, causing acute aortic insufficiency; and (3) rupture of the hematoma into the pericardial space,

leading to pericardial tamponade.

Knowledge of the epidemiology of acute aortic syndromes can be

helpful in maintaining awareness of this relatively uncommon group

of disorders (estimated annual incidence, 3 cases per 100,000 population). Nontraumatic aortic dissections are very rare in the absence of

hypertension or conditions associated with deterioration of the elastic

or muscular components of the aortic media, including pregnancy,

bicuspid aortic disease, or inherited connective tissue diseases, such as

Marfan and Ehlers-Danlos syndromes.

Although aortic aneurysms are most often asymptomatic, thoracic

aortic aneurysms can cause chest pain and other symptoms by compressing adjacent structures. This pain tends to be steady, deep, and

occasionally severe. Aortitis, whether of noninfectious or infectious

etiology, in the absence of aortic dissection is a rare cause of chest or

back discomfort.

Pulmonary Conditions Pulmonary and pulmonary-vascular

conditions that cause chest discomfort usually do so in conjunction

with dyspnea and often produce symptoms that have a pleuritic nature.

PULMONARY EMBOLISM (SEE ALSO CHAP. 279) Pulmonary emboli

(annual incidence, ~1 per 1000) can produce dyspnea and chest discomfort that is sudden in onset. Typically pleuritic in pattern, the chest

discomfort associated with pulmonary embolism may result from

(1) involvement of the pleural surface of the lung adjacent to a resultant pulmonary infarction; (2) distention of the pulmonary artery; or

(3) possibly, right ventricular wall stress and/or subendocardial ischemia related to acute pulmonary hypertension. The pain associated with

small pulmonary emboli is often lateral and pleuritic and is believed to

be related to the first of these three possible mechanisms. In contrast,

massive pulmonary emboli may cause severe substernal pain that may

mimic an MI and that is plausibly attributed to the second and third

of these potential mechanisms. Massive or submassive pulmonary

embolism may also be associated with syncope, hypotension, and signs

of right heart failure. Other typical characteristics that aid in the recognition of pulmonary embolism are discussed later in this chapter (see

“Approach to the Patient”).

103Chest Discomfort CHAPTER 14

TABLE 14-2 Considerations in the Assessment of the Patient with

Chest Discomfort

1. Could the chest discomfort be due to an acute, potentially

life-threatening condition that warrants urgent evaluation and

management?

Unstable ischemic

heart disease

Aortic dissection Pneumothorax Pulmonary

embolism

2. If not, could the discomfort be due to a chronic condition likely to

lead to serious complications?

Stable angina Aortic stenosis Pulmonary

hypertension

3. If not, could the discomfort be due to an acute condition that warrants

specific treatment?

Pericarditis Pneumonia/

pleuritis

Herpes zoster

4. If not, could the discomfort be due to another treatable chronic

condition?

Esophageal reflux Cervical disk disease

Esophageal spasm Arthritis of the shoulder or spine

Peptic ulcer disease Costochondritis

Gallbladder disease Other musculoskeletal disorders

Other gastrointestinal conditions Anxiety state

Source: Developed by Dr. Thomas H. Lee for the 18th edition of Harrison’s Principles

of Internal Medicine.

PNEUMOTHORAX (SEE ALSO CHAP. 294) Primary spontaneous pneumothorax is a rare cause of chest discomfort, with an estimated annual

incidence in the United States of 7 per 100,000 among men and

<2 per 100,000 among women. Risk factors include male sex, smoking,

family history, and Marfan syndrome. The symptoms are usually sudden in onset, and dyspnea may be mild; thus, presentation to medical

attention is sometimes delayed. Secondary spontaneous pneumothorax

may occur in patients with underlying lung disorders, such as chronic

obstructive pulmonary disease, asthma, or cystic fibrosis, and usually

produces symptoms that are more severe. Tension pneumothorax is a

medical emergency caused by trapped intrathoracic air that precipitates hemodynamic collapse.

Other Pulmonary Parenchymal, Pleural, or Vascular Disease

(See also Chaps. 283, 284, and 294) Most pulmonary diseases

that produce chest pain, including pneumonia and malignancy, do

so because of involvement of the pleura or surrounding structures.

Pleurisy is typically described as a knifelike pain that is worsened by

inspiration or coughing. In contrast, chronic pulmonary hypertension

can manifest as chest pain that may be very similar to angina in its

characteristics, suggesting right ventricular myocardial ischemia in

some cases. Reactive airways diseases similarly can cause chest tightness associated with breathlessness rather than pleurisy.

■ NONCARDIOPULMONARY CAUSES

Gastrointestinal Conditions (See also Chap. 321) Gastrointestinal disorders are the most common cause of nontraumatic chest

discomfort and often produce symptoms that are difficult to discern

from more serious causes of chest pain, including myocardial ischemia.

Esophageal disorders, in particular, may simulate angina in the character and location of the pain. Gastroesophageal reflux and disorders of

esophageal motility are common and should be considered in the differential diagnosis of chest pain (Fig. 14-1 and Table 14-1). The pain of

esophageal spasm is commonly an intense, squeezing discomfort that

is retrosternal in location and, like angina, may be relieved by nitroglycerin or dihydropyridine calcium channel antagonists. Chest pain

can also result from injury to the esophagus, such as a Mallory-Weiss

tear or even an esophageal rupture (Boerhaave’s syndrome) caused by

severe vomiting. Peptic ulcer disease is most commonly epigastric in

location but can radiate into the chest (Table 14-1).

Hepatobiliary disorders, including cholecystitis and biliary colic,

may mimic acute cardiopulmonary diseases. Although the pain arising

from these disorders usually localizes to the right upper quadrant of the

abdomen, it is variable and may be felt in the epigastrium and radiate

to the back and lower chest. This discomfort is sometimes referred

to the scapula or may in rare cases be felt in the shoulder, suggesting

diaphragmatic irritation. The pain is steady, usually lasts several hours,

and subsides spontaneously, without symptoms between attacks. Pain

resulting from pancreatitis is typically aching epigastric pain that radiates to the back.

Musculoskeletal and Other Causes (See also Chap. 360)

Chest discomfort can be produced by any musculoskeletal disorder

involving the chest wall or the nerves of the chest wall, neck, or upper

limbs. Costochondritis causing tenderness of the costochondral junctions (Tietze’s syndrome) is relatively common. Cervical radiculitis may

manifest as a prolonged or constant aching discomfort in the upper

chest and limbs. The pain may be exacerbated by motion of the neck.

Occasionally, chest pain can be caused by compression of the brachial

plexus by the cervical ribs, and tendinitis or bursitis involving the left

shoulder may mimic the radiation of angina. Pain in a dermatomal

distribution can also be caused by cramping of intercostal muscles or

by herpes zoster (Chap. 193).

Emotional and Psychiatric Conditions As many as 10% of

patients who present to EDs with acute chest discomfort have a panic

disorder or related condition (Table 14-1). The symptoms may include

chest tightness or aching that is associated with a sense of anxiety and

difficulty breathing. The symptoms may be prolonged or fleeting.

APPROACH TO THE PATIENT

Chest Discomfort

Given the broad set of potential causes and the heterogeneous

risk of serious complications in patients who present with acute

nontraumatic chest discomfort, the priorities of the initial clinical

encounter include assessment of (1) the patient’s clinical stability

and (2) the probability that the patient has an underlying cause of

the discomfort that may be life-threatening. The high-risk conditions of principal concern are acute cardiopulmonary processes,

including ACS, acute aortic syndrome, pulmonary embolism, tension pneumothorax, and pericarditis with tamponade. Fulminant

myocarditis also carries a poor prognosis but is usually also manifest

by heart failure symptoms. Among noncardiopulmonary causes of

chest pain, esophageal rupture likely holds the greatest urgency for

diagnosis. Patients with these conditions may deteriorate rapidly

despite initially appearing well. The remaining population with noncardiopulmonary conditions has a more favorable prognosis during

completion of the diagnostic workup. A rapid targeted assessment

for a serious cardiopulmonary cause is of particular relevance for

patients with acute ongoing pain who have presented for emergency

evaluation. Among patients presenting in the outpatient setting

with chronic pain or pain that has resolved, a general diagnostic

assessment is reasonably undertaken (see “Outpatient Evaluation of

Chest Discomfort,” below). A series of questions that can be used to

structure the clinical evaluation of patients with chest discomfort is

shown in Table 14-2.

HISTORY

The evaluation of nontraumatic chest discomfort relies heavily on

the clinical history and physical examination to direct subsequent

diagnostic testing. The evaluating clinician should assess the quality, location (including radiation), and pattern (including onset and

duration) of the pain as well as any provoking or alleviating factors.

The presence of associated symptoms may also be useful in establishing a diagnosis.

Quality of Pain The quality of chest discomfort alone is never

sufficient to establish a diagnosis. However, the characteristics of

the pain are pivotal in formulating an initial clinical impression

and assessing the likelihood of a serious cardiopulmonary process

104 PART 2 Cardinal Manifestations and Presentation of Diseases

Radiation to right arm or shoulder

Radiation to both arms or shoulders

Associated with exertion

Radiation to left arm

Associated with diaphoresis

Associated with nausea or vomiting

Worse than previous angina

or similar to previous MI

Described as pressure

Inframammary location

Reproducible with palpation

Described as sharp

Described as positional

Described as pleuritic

Likelihood ratio for AMI

0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5

INCREASED LIKELIHOOD OF AMI

DECREASED LIKELIHOOD OF AMI

FIGURE 14-2 Association of chest pain characteristics with the probability of acute myocardial infarction (AMI). Note that a subsequent larger study showed a

nonsignificant association with radiation to the right arm. (Figure prepared from data in CJ Swap, JT Nagurney: JAMA 294:2623, 2005.)

(Table 14-1), including ACS in particular (Fig. 14-2). Pressure or

tightness is consistent with a typical presentation of myocardial

ischemic pain. Nevertheless, the clinician must remember that some

patients with ischemic chest symptoms deny any “pain” but rather

complain of dyspnea or a vague sense of anxiety. The severity of the

discomfort has poor diagnostic accuracy. It is often helpful to ask

about the similarity of the discomfort to previous definite ischemic

symptoms. It is unusual for angina to be sharp, as in knifelike, stabbing, or pleuritic; however, patients sometimes use the word “sharp”

to convey the intensity of discomfort rather than the quality. Pleuritic

discomfort is suggestive of a process involving the pleura, including

pericarditis, pulmonary embolism, or pulmonary parenchymal

processes. Less frequently, the pain of pericarditis or massive pulmonary embolism is a steady severe pressure or aching that can be

difficult to discriminate from myocardial ischemia. “Tearing” or

“ripping” pain is often described by patients with acute aortic dissection. However, acute aortic emergencies also present commonly

with knifelike pain. A burning quality can suggest acid reflux or

peptic ulcer disease but may also occur with myocardial ischemia.

Esophageal pain, particularly with spasm, can be a severe squeezing

discomfort identical to angina.

Location of Discomfort A substernal location with radiation to

the neck, jaw, shoulder, or arms is typical of myocardial ischemic

discomfort. Radiation to both arms has a particularly high association with MI as the etiology. Some patients present with aching in

sites of radiated pain as their only symptoms of ischemia. However,

pain that is highly localized—e.g., that which can be demarcated by

the tip of one finger—is highly unusual for angina. A retrosternal

location should prompt consideration of esophageal pain; however,

other gastrointestinal conditions usually present with pain that is

most intense in the abdomen or epigastrium, with possible radiation into the chest. Angina may also occur in an epigastric location.

Pain that occurs solely above the mandible or below the epigastrium

is rarely angina. Severe pain radiating to the back, particularly

between the shoulder blades, should prompt consideration of an

acute aortic syndrome. Radiation to the trapezius ridge is characteristic of pericardial pain and does not usually occur with angina.

Pattern Myocardial ischemic discomfort usually builds over minutes and is exacerbated by activity and mitigated by rest. In contrast,

pain that reaches its peak intensity immediately is more suggestive

of aortic dissection, pulmonary embolism, or spontaneous pneumothorax. Pain that is fleeting (lasting only a few seconds) is rarely

ischemic in origin. Similarly, pain that is constant in intensity for

a prolonged period (many hours to days) is unlikely to represent

myocardial ischemia if it occurs in the absence of other clinical consequences, such as abnormalities of the ECG, elevation of cardiac

biomarkers, or clinical sequelae (e.g., heart failure or hypotension).

Both myocardial ischemia and acid reflux may have their onset in

the morning.

Provoking and Alleviating Factors Patients with myocardial

ischemic pain usually prefer to rest, sit, or stop walking. However,

clinicians should be aware of the phenomenon of “warm-up angina”

in which some patients experience relief of angina as they continue

at the same or even a greater level of exertion (Chap. 273). Alterations in the intensity of pain with changes in position or movement

of the upper extremities and neck are less likely with myocardial

ischemia and suggest a musculoskeletal etiology. The pain of pericarditis, however, often is worse in the supine position and relieved

by sitting upright and leaning forward. Gastroesophageal reflux

may be exacerbated by alcohol, some foods, or a reclined position.

Relief can occur with sitting.

Exacerbation by eating suggests a gastrointestinal etiology such

as peptic ulcer disease, cholecystitis, or pancreatitis. Peptic ulcer

disease tends to become symptomatic 60–90 min after meals. However, in the setting of severe coronary atherosclerosis, redistribution

of blood flow to the splanchnic vasculature after eating can trigger

postprandial angina. The discomfort of acid reflux and peptic ulcer

disease is usually diminished promptly by acid-reducing therapies.

In contrast with its impact in some patients with angina, physical

exertion is very unlikely to alter symptoms from gastrointestinal

causes of chest pain. Relief of chest discomfort within minutes

after administration of nitroglycerin is suggestive of but not sufficiently sensitive or specific for a definitive diagnosis of myocardial

ischemia. Esophageal spasm may also be relieved promptly with

105Chest Discomfort CHAPTER 14

nitroglycerin. A delay of >10 min before relief is obtained after

nitroglycerin suggests that the symptoms either are not caused by

ischemia or are caused by severe ischemia, such as during acute MI.

Associated Symptoms Symptoms that accompany myocardial

ischemia may include diaphoresis, dyspnea, nausea, fatigue, faintness, and eructations. In addition, these symptoms may exist in isolation as anginal equivalents (i.e., symptoms of myocardial ischemia

other than typical angina), particularly in women and the elderly.

Dyspnea may occur with multiple conditions considered in the differential diagnosis of chest pain and thus is not discriminative, but

the presence of dyspnea is important because it suggests a cardiopulmonary etiology. Sudden onset of significant respiratory distress

should lead to consideration of pulmonary embolism and spontaneous pneumothorax. Hemoptysis may occur with pulmonary

embolism or as blood-tinged frothy sputum in severe heart failure

but usually points toward a pulmonary parenchymal etiology of

chest symptoms. Presentation with syncope or presyncope should

prompt consideration of hemodynamically significant pulmonary

embolism or aortic dissection as well as ischemic arrhythmias.

Although nausea and vomiting suggest a gastrointestinal disorder,

these symptoms may occur in the setting of MI (more commonly

inferior MI), presumably because of activation of the vagal reflex

or stimulation of left ventricular receptors as part of the BezoldJarisch reflex.

Past Medical History The past medical history is useful in assessing the patient for risk factors for coronary atherosclerosis and

venous thromboembolism (Chap. 279) as well as for conditions

that may predispose the patient to specific disorders. For example,

a history of connective tissue diseases such as Marfan syndrome

should heighten the clinician’s suspicion of an acute aortic syndrome or spontaneous pneumothorax. A careful history may elicit

clues about depression or prior panic attacks.

PHYSICAL EXAMINATION

In addition to providing an initial assessment of the patient’s clinical

stability, the physical examination of patients with chest discomfort

can provide direct evidence of specific etiologies of chest pain

(e.g., unilateral absence of lung sounds) and can identify potential

precipitants of acute cardiopulmonary causes of chest pain (e.g.,

uncontrolled hypertension), relevant comorbid conditions (e.g.,

obstructive pulmonary disease), and complications of the presenting syndrome (e.g., heart failure). However, because the findings

on physical examination may be normal in patients with unstable

ischemic heart disease, an unremarkable physical exam is not definitively reassuring.

General The patient’s general appearance is helpful in establishing an initial impression of the severity of illness. Patients with

acute MI or other acute cardiopulmonary disorders often appear

anxious, uncomfortable, pale, cyanotic, or diaphoretic. Patients

who are massaging or clutching their chests may describe their

pain with a clenched fist held against the sternum (Levine’s sign).

Occasionally, body habitus is helpful—e.g., in patients with Marfan

syndrome or the prototypical young, tall, thin man with spontaneous pneumothorax.

Vital Signs Significant tachycardia and hypotension are indicative

of important hemodynamic consequences of the underlying cause

of chest discomfort and should prompt a rapid survey for the most

severe conditions, such as acute MI with cardiogenic shock, massive pulmonary embolism, pericarditis with tamponade, or tension

pneumothorax. Acute aortic emergencies usually present with

severe hypertension but may be associated with profound hypotension when there is coronary arterial compromise or dissection into

the pericardium. Sinus tachycardia is an important manifestation of

submassive pulmonary embolism. Tachypnea and hypoxemia point

toward a pulmonary cause. The presence of low-grade fever is nonspecific because it may occur with MI and with thromboembolism

in addition to infection.

Pulmonary Examination of the lungs may localize a primary

pulmonary cause of chest discomfort, as in cases of pneumonia,

asthma, or pneumothorax. Left ventricular dysfunction from severe

ischemia/infarction as well as acute valvular complications of MI or

aortic dissection can lead to pulmonary edema, which is an indicator of high risk.

Cardiac The jugular venous pulse is often normal in patients with

acute myocardial ischemia but may reveal characteristic patterns

with pericardial tamponade or acute right ventricular dysfunction

(Chaps. 239 and 270). Cardiac auscultation may reveal a third or,

more commonly, a fourth heart sound, reflecting myocardial systolic or diastolic dysfunction. Murmurs of mitral regurgitation or a

ventricular-septal defect may indicate mechanical complications of

STEMI. A murmur of aortic insufficiency may be a complication of

ascending aortic dissection. Other murmurs may reveal underlying

cardiac disorders contributory to ischemia (e.g., aortic stenosis or

hypertrophic cardiomyopathy). Pericardial friction rubs reflect

pericardial inflammation.

Abdominal Localizing tenderness on the abdominal exam is

useful in identifying a gastrointestinal cause of the presenting

syndrome. Abdominal findings are infrequent with purely acute

cardiopulmonary problems, except in the case of right-sided heart

failure leading to hepatic congestion.

Extremities Vascular pulse deficits may reflect underlying chronic

atherosclerosis, which increases the likelihood of coronary artery disease. However, evidence of acute limb ischemia with loss of the pulse

and pallor, particularly in the upper extremities, can indicate catastrophic consequences of aortic dissection. Unilateral lower-extremity

swelling should raise suspicion about venous thromboembolism.

Musculoskeletal Pain arising from the costochondral and chondrosternal articulations may be associated with localized swelling,

redness, or marked localized tenderness. Pain on palpation of these

joints is usually well localized and is a useful clinical sign, although

deep palpation may elicit pain in the absence of costochondritis.

Although palpation of the chest wall often elicits pain in patients

with various musculoskeletal conditions, it should be appreciated

that chest wall tenderness does not exclude myocardial ischemia.

Sensory deficits in the upper extremities may be indicative of cervical disk disease.

ELECTROCARDIOGRAPHY

Electrocardiography is crucial in the evaluation of nontraumatic

chest discomfort. The ECG is pivotal for identifying patients with

ongoing ischemia as the principal reason for their presentation as

well as secondary cardiac complications of other disorders. Professional society guidelines recommend that an ECG be obtained

within 10 min of presentation, with the primary goal of identifying patients with ST-segment elevation diagnostic of MI who

are candidates for immediate interventions to restore flow in the

occluded coronary artery. ST-segment depression and symmetric

T-wave inversions at least 0.2 mV in depth are useful for detecting

myocardial ischemia in the absence of STEMI and are also indicative of higher risk of death or recurrent ischemia. Serial performance of ECGs (every 30–60 min) is recommended in the ED

evaluation of suspected ACS. In addition, an ECG with right-sided

lead placement should be considered in patients with clinically

suspected ischemia and a nondiagnostic standard 12-lead ECG.

Despite the value of the resting ECG, its sensitivity for ischemia is

poor—as low as 20% in some studies.

Abnormalities of the ST segment and T wave may occur in a

variety of conditions, including pulmonary embolism, ventricular

hypertrophy, acute and chronic pericarditis, myocarditis, electrolyte imbalance, and metabolic disorders. Notably, hyperventilation

associated with panic disorder can also lead to nonspecific ST and

T-wave abnormalities. Pulmonary embolism is most often associated with sinus tachycardia but can also lead to rightward shift of

the ECG axis, manifesting as an S-wave in lead I, with a Q-wave

106 PART 2 Cardinal Manifestations and Presentation of Diseases

Elevated cTn Concentration

Dynamic cTn (significant rise or fall)

Ischemia

Myocardial

infarction

Acute

myocardial

injury

Chronic

myocardial

Type 1 injury

MI

Type 2

MI

No ischemia

Stable cTn

FIGURE 14-3 Clinical classification of patients with elevated cardiac troponin

(cTn). MI, myocardial infarction.

and T-wave in lead III (Chaps. 240 and 279). In patients with

ST-segment elevation, the presence of diffuse lead involvement not

corresponding to a specific coronary anatomic distribution and

PR-segment depression can aid in distinguishing pericarditis from

acute MI.

CHEST RADIOGRAPHY

(See Chap. A12) Plain radiography of the chest is performed

routinely when patients present with acute chest discomfort and

selectively when individuals who are being evaluated as outpatients

have subacute or chronic pain. The chest radiograph is most useful

for identifying pulmonary processes, such as pneumonia or pneumothorax. Findings are often unremarkable in patients with ACS,

but pulmonary edema may be evident. Other specific findings

include widening of the mediastinum in some patients with aortic

dissection, Hampton’s hump or Westermark’s sign in patients with

pulmonary embolism (Chaps. 279 and A12), or pericardial calcification in chronic pericarditis.

CARDIAC BIOMARKERS

Laboratory testing in patients with acute chest pain is focused on

the detection of myocardial injury. Such injury can be detected by

the presence of circulating proteins released from damaged cardiomyocytes. Owing to the time necessary for this release, initial

biomarkers of injury may be in the normal range, even in patients

with STEMI. Cardiac troponin is the preferred biomarker for the

diagnosis of MI and should be measured in all patients with suspected ACS. It is not necessary or advisable to measure troponin

in patients without suspicion of ACS unless this test is being used

specifically for risk stratification (e.g., in pulmonary embolism or

heart failure).

The development of cardiac troponin assays with progressively

greater analytical sensitivity has facilitated detection of substantially

lower blood concentrations of troponin than was previously possible. This evolution permits earlier detection of myocardial injury

and more reliable discrimination of changing values, enhances the

overall accuracy of a diagnosis of MI, and improves risk stratification in suspected ACS. For these reasons, high-sensitivity assays

are generally preferred over prior generation troponin assays. The

greater negative predictive value of a negative troponin result with

high-sensitivity assays is an advantage in the evaluation of chest

pain in the ED. Rapid rule-out protocols that use serial testing

and changes in troponin concentration over as short a period as

1–2 h appear to perform well for diagnosis of ACS when using a

high-sensitivity troponin assay. Troponin should be measured at

presentation and repeated at 1–3 h using high-sensitivity troponin

and 3–6 h using conventional troponin assays. Additional troponin

measurements may be warranted beyond 3–6 h when the clinical

condition still suggests possible ACS or if there is diagnostic uncertainty. In patients presenting more than 2–3 h after symptom onset,

a concentration of cardiac troponin, at the time of hospital presentation, below the limit of detection using a high-sensitivity assay may

be sufficient to exclude MI with a negative predictive value >99%.

With the use of high-sensitivity assays for troponin, myocardial

injury is detected in a larger proportion of patients who have nonACS cardiopulmonary conditions than with previous, less sensitive

assays. Therefore, other aspects of the clinical evaluation are critical to the practitioner’s determination of the probability that the

symptoms represent ACS. In addition, observation of a change in

cardiac troponin concentration between serial samples is necessary

for discriminating acute causes of myocardial injury from chronic

elevation due to underlying structural heart disease, end-stage renal

disease, or the rare presence of interfering antibodies. The diagnosis of MI is reserved for acute myocardial injury that is marked by

a rising and/or falling pattern—with at least one value exceeding

the 99th percentile reference limit—and that is caused by ischemia.

Other nonischemic insults, such as myocarditis, may result in acute

myocardial injury but should not be labeled MI (Fig. 14-3).

Other laboratory assessments may include the D-dimer test to

aid in exclusion of pulmonary embolism (Chap. 279). Measurement of a B-type natriuretic peptide is useful when considered in

conjunction with the clinical history and exam for the diagnosis of

heart failure. B-type natriuretic peptides also provide prognostic

information among patients with ACS and those with pulmonary

embolism.

INTEGRATIVE DECISION-AIDS

Multiple clinical algorithms have been developed to aid in decisionmaking during the evaluation and disposition of patients with acute

nontraumatic chest pain. Such decision-aids estimate either of two

closely related but not identical probabilities: (1) the probability of

a final diagnosis of ACS and (2) the probability of major cardiac

events during short-term follow-up. Such decision-aids are used

most commonly to identify patients with a low clinical probability

of ACS who are candidates for discharge from the ED, with or

without additional noninvasive testing. Goldman and Lee developed one of the first such decision-aids, using only the ECG and

risk indicators—hypotension, pulmonary rales, and known ischemic heart disease—to categorize patients into four risk categories

ranging from a <1% to a >16% probability of a major cardiovascular complication. Decision-aids used more commonly in current

practice are shown in Fig. 14-4. Elements common across multiple

risk stratification tools are (1) symptoms typical for ACS; (2) older

age; (3) risk factors for or known atherosclerosis; (4) ischemic ECG

abnormalities; and (5) elevated cardiac troponin level. Although,

because of very low specificity, the overall diagnostic performance

of such decision-aids is poor (area under the receiver operating

curve, 0.55–0.65), in conjunction with the ECG and serial highsensitivity cardiac troponin, they can help identify patients with

a very low probability of ACS (e.g., <1%) or adverse cardiovascular events (<2% at 30 days). Clinical application of such integrated decision-aids or “accelerated diagnostic protocols” has been

reported to achieve overall “miss rates” for ACS of <0.5% and may

be useful for identifying patients who may be discharged without

the need for additional cardiac testing.

Clinicians should differentiate between the algorithms discussed

above and risk scores derived for stratification of prognosis (e.g., the

TIMI and GRACE risk scores, Chap. 275) in patients who already

have an established diagnosis of ACS. The latter risk scores were not

designed to be used for diagnostic assessment.

CORONARY AND MYOCARDIAL STRESS IMAGING

Among patients for whom other life-threatening causes of chest

pain have been reasonably excluded and serial biomarker and

clinical assessment have determined the patient to remain eligible

for further testing because of intermediate or undetermined risk,

diagnostic coronary imaging with coronary computed tomographic

(CT) angiography or functional testing, preferably with nuclear or

echocardiographic imaging, is recommended. Patient characteristics (e.g., body habitus and renal function), prior cardiac testing,

107Chest Discomfort CHAPTER 14

history of known coronary artery disease, existing contraindications for a given test modality, and patient preferences are considerations when choosing among these diagnostic tests (Chaps. 241

and A9).

CT Angiography (See Chap. 241) CT angiography has emerged as

a preferred modality for the evaluation of patients with acute chest

discomfort who are candidates for further testing after biomarker

and clinical risk assessment. Coronary CT angiography is a sensitive technique for detection of obstructive coronary disease. CT

appears to enhance the speed to disposition of patients with a

low-intermediate probability for ACS, with its major strength being

the negative predictive value of a finding of no significant stenosis

or coronary plaque. In addition, contrast-enhanced CT can detect

focal areas of myocardial injury in the acute setting. At the same

time, CT angiography can exclude aortic dissection, pericardial

effusion, and pulmonary embolism.

Stress Nuclear Perfusion Imaging or Stress Echocardiography

(See Chaps. 241 and A9) Functional testing with stress nuclear

perfusion imaging and stress echocardiography are alternatives for

the evaluation of patients with acute chest pain who are candidates

for further testing and are preferred over coronary CT angiography

in patients with known obstructive epicardial disease. The selection

of stress test modality may depend on institutional availability

and expertise. Stress testing with myocardial imaging, either with

nuclear perfusion imaging or echocardiography, offers superior

diagnostic performance over exercise ECG. In patients selected for

stress myocardial imaging who are able to exercise, exercise stress

is preferred over pharmacologic testing. When available, positron

emission tomography offers advantages of improved diagnostic

performance and fewer nondiagnostic studies than single-photon

emission CT.

Although functional testing is generally contraindicated in

patients with ongoing chest pain, in selected patients with persistent

pain and nondiagnostic ECG and biomarker data, resting myocardial perfusion images can be obtained; the absence of any perfusion

abnormality substantially reduces the likelihood of coronary artery

disease. In such a strategy, used in some centers, those with abnormal

rest perfusion imaging, which cannot discriminate between old or

new myocardial defects, usually must undergo additional evaluation.

EXERCISE ELECTROCARDIOGRAPHY

Exercise electrocardiography has historically been commonly

employed for completion of risk stratification of patients who have

undergone an initial evaluation that has not revealed a specific

cause of chest discomfort and has identified a low risk of ACS.

Early exercise testing is safe in patients without ongoing chest pain

or high-risk findings and may assist in refining their prognostic

assessment. However, for patients with chest pain for whom both

cardiac troponin and clinical risk stratification have determined the

patient to have low probability of ACS, there is insufficient evidence

that stress testing or cardiac imaging improves their outcomes.

This evolution in evidence supports a change from past practice in

which outpatient stress testing within 72 hours was broadly used for

patients with acute chest pain.

OTHER NONINVASIVE STUDIES

Other noninvasive imaging studies of the chest can be used selectively to provide additional diagnostic and prognostic information

on patients with chest discomfort.

HEART Score (without cTn)

History Highly suspicious

Moderately suspicious

Slightly suspicious

2

1

0

ECG Significant ST depression

Nonspecific abnormality

Normal

2

1

0

Age ≥65 y

45–<65 y

<45 y

2

1

0

Risk

factors

≥3 risk factors

1–2 risk factors

None

2

1

0

TOTAL

Low risk: 0–3

Not low risk: ≥4

EDACS Score

Age 86+ y

81–85 y

76–80 y

Step down by 5-y increments

46–50 y

18–45 y

20

18

16

(–2)

4

2

Known

CAD or

risk

factors

Known CAD (prior MI, PCI,

or CABG) or ≥3 cardiac risk

factors in patient aged ≤50 y

4

Sex Male

Female

6

0

Symptoms Radiation to arm, shoulder,

neck, or jaw

Diaphoresis

Pain with inspiration

Reproduced by palpation

5

3

–4

–6

TOTAL

Low risk: 0–15

Not low risk: ≥16

NPV

Captured as

low risk (%)

99.55

51.8

99.49

60.6

AND cardiac troponin < the limit of quantification.*

FIGURE 14-4 Examples of decision-aids used in conjunction with serial measurement of cardiac troponin (cTn) for evaluation of acute chest pain. The HEART score

was modified by the authors in the presented study and omitting the assignment of 0, 1, or 2 points based on troponin. The negative predictive value (NPV) reported

is for the composite endpoint of myocardial infarction (MI), cardiogenic shock, cardiac arrest, and all-cause mortality by 60 days. *Limit of quantification is the lowest

analyte concentration that can be quantitatively detected with a total imprecision of ≤20%. CABG, coronary artery bypass graft; CAD, coronary artery disease; ECG,

electrocardiogram; PCI, percutaneous coronary intervention. (Figure prepared from data in DG Mark et al: J Am Coll Cardiol 13:606, 2018.)