The Netter Collection of Medical Illustrations VOLUME 9 Digestive System Part I - The Upper Digestive Tract ( PDFDrive )_compressed

Plate 1-41  Upper Digestive Tract: PART I

Posterior scrotal nerves NERVES OF PERINEUM: MALE
Perineal Superficial Dorsal nerve of penis
nerves Deep Perineal membrane (cut to show neurovascular
structures on superior aspect of perineal membrane)
Innervation of Abdomen and
Perineum (Continued) Dorsal nerve of
penis (continuation
anteriorly and medially inferior to the ischial tuberosity of pudendal nerve
to the skin and fasciae of the perineum, scrotum, and supplying muscles
root of the penis. The distribution is similar in the on superior aspect
female, to the perineum, labia majora, and root of the of perineal
clitoris. Its terminal twigs communicate with the infe- membrane)
rior rectal and perineal branches of the pudendal and
terminal filaments of the ilioinguinal nerves. The per- Superficial
forating cutaneous nerve pierces the sacrotuberous liga- perineal (Colles)
ment and turns around the lower margin of the gluteus fascia (cut to
maximus to become cutaneous a short distance lateral open superficial
to the coccyx. Its origin and distribution, however, are perineal space)
not constant. It may be joined or replaced by branches
from the pudendal nerve, posterior femoral cutaneous Superficial
nerve, or perineal branch of the fourth sacral nerve, arising and deep
from a loop between the third and fourth sacral nerves. branches of
This branch reaches the posterior angle of the ischio- perineal nerve
anal fossa by perforating the coccygeus muscle and then Dorsal nerve of
divides into some twigs that run anteriorly to assist the penis (passes
innervation of the external anal sphincter and others superior to
that ramify in the overlying skin and fascia. perineal
membrane)
The coccygeal plexus is formed by the union of the
inferior part of the anterior ramus of the fourth sacral Perineal nerve
nerve with those of the fifth sacral and coccygeal nerves.
The plexus is small and really consists of two loops on Posterior
the pelvic surface of the coccygeus and the levator ani femoral
muscles. It gives off fine twigs to the parts adjacent to cutaneous
both these structures, as well as the delicate anococcy- nerve
geal nerves that pierce the sacrotuberous ligament and Obturator
supply the skin in the vicinity of the coccyx. fascia (of
obturator
Having discussed the nerves supplying the wall of the internus
abdominal cavity, the lumbar, sacral, and coccygeal muscle)
plexuses, and the nerves they release to innervate part Pudendal canal
of the abdominal viscera and floor (pelvis as well as (Alcock)
perineum) of the abdominal cavity, it remains to con- (opened up)
sider the innervation of the diaphragm, which forms the
roof of the abdominal cavity. The diaphragm is supplied Inferior Pudendal nerve
by the phrenic and lower intercostal nerves. Each clunial nerves Sacrotuberous ligament (cut)
phrenic nerve contains both motor and sensory fibers; on gluteus
the latter convey afferent impulses from the pleura, maximus muscle
pericardium, peritoneum, and other structures. The Inferior anal (rectal) nerves
motor fibers are the axons of the phrenic nucleus in the
third, fourth, and fifth cervical cord segments. If one Perforating cutaneous nerve
phrenic nerve is destroyed, complete muscular atrophy
Anococcygeal nerve

Piriformis muscle

Coccygeus Ischial
(ischiococcygeus) spine
muscle Pudendal
Levator ani muscle nerve
Obturator
internus muscle

occurs in the corresponding half of the diaphragm, so arising from the arcuate ligaments. The left nerve
it is presumed the intercostal nerve supply must be pierces the diaphragm about 3 cm anterior to the
sensory. central tendon and thereafter supplies the left half of
the muscle, including the fibers of the right crus lying
The phrenic nerves are distributed mainly on the to the left of the esophageal hiatus. The phrenic
inferior surface of the diaphragm. The right pierces the branches communicate with autonomic fibers from the
central tendon just lateral to the caval hiatus and divides celiac plexus accompanying the inferior phrenic arter-
into anterior and posterior branches that supply all the ies. On the right side a small ganglion marks one of
muscle fibers on the same side, including the crural these interconnections.
fibers on the right side of the esophagus and those

42 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 1-42  Overview of Upper Digestive Tract

Overview of the Digestive Liver Mouth and pharynx
System Secretion of bile (important Mechanical breakdown,
for lipid digestion), storage mixing with salivary secretions
The digestive system is by far the largest and most of nutrients, production of Salivary glands
complex of the internal organ systems. The interplay of Secretion of lubricating fluid
its multiple organs, its intrinsic hormonal and neural cellular fuels, plasma containing enzymes that
systems, and its intricate and interacting physiologic proteins, clotting factors, initiate digestion
functions are among the most fascinating aspects of
human physiology. Although the primary function of and detoxification and Esophagus
each organ is to interact effectively with other organs phagocytosis Transport of food and
to provide nutrition to the rest of the body, several fluid into the stomach;
organs also have distinct metabolic functions that are of Gallbladder prevents reflux
vital importance. Storage and
concentration of bile Stomach
Appreciating the role of each organ begins with Large intestine Chemical breakdown of
asking how the four essential functions of each are regu- Dehydration and food by acid and enzymes;
lated and how immune and other defense mechanisms compaction of indigestible mechanical breakdown
are protecting that organ. The wall of each luminal materials for elimination; via muscular contractions
organ is composed of three layers of distinctly function- resorption of water and
ing muscle groups responsible for moving nutrients and electrolytes; host defense Pancreas
fluids from the mouth until they are discharged from Secretion/ Secretion of buffers and digestive
the anus. The electromechanical coupling mechanisms digestion enzymes by exocrine cells; secretion
responsible for motility by which this occurs are Absorption of hormones by endocrine cells to
surprisingly distinct for each organ. An electrical syn- regulate digestion and metabolism
cytium regulates these contractions with rhythmic
depolarizations called slow waves and contraction- Small intestine
inducing depolarizations resulting in action potentials. Enzymatic digestion and
Action potentials are similar throughout the luminal absorption of water, organic
organs, but slow wave activities in the stomach, duode- substrates, vitamins, and ions; host
num, and colon vary in frequency. defense

All luminal and solid gastrointestinal organs are Mucosal and
involved with secretions that facilitate digestion and hepatic protective
mucosal protection, leading to nutrient absorption. In
contrast, the esophagus has the least secretion and no mechanisms
absorption and the liver and pancreas are involved with
secretion only and not motility or absorption. Digestive Motility
System Metabolism
The liver is the most important and largest metabolic
organ. Metabolic functions are also provided by pro- Functions
teins synthesized by the small bowel and by hormones
secreted by the stomach, pancreas, and small bowel. Regulation
control
Regulation of each organ is achieved with a complex
interaction between the extrinsic autonomic nervous mechanisms
system, intrinsic or enteric nervous system, and hor-
mones secreted both within and outside the digestive each organ include motility, intrinsic secretion, lubrica- nal disorders account for 25% of all hospitalizations. Of
system. The hormones of the digestive system were the tion with fluid and mucus, and frequent cell turnover. all primary neoplasms leading to death, one third origi-
first endocrine substances to be discovered. The small nate in digestive system organs. Cancers of the digestive
intestine is clearly the largest of all endocrine organs. When these protective systems break down or system continue to be the most common cause of all
Each of the neurotransmitters identified in the enteric become impaired, disease begins. Disorders of the cancer deaths. Lung cancer is overall the most common
nervous system of the digestive system is also found in digestive tract are the second most common reason, type of cancer, but cancers of the colon, pancreas, liver,
the brain. Again, many were first discovered in the gut. after upper respiratory tract disorders, that patients stomach, and esophagus are among the 10 commonest
seek help from a primary care physician or are absent cancers.
The lumen of each of the digestive organs is filled from work or school. In a typical year, approximately
with potentially lethal chemicals and microorganisms. 60% of individuals experience some digestive system One of the most fascinating aspects of the patho-
Distinct, organ-specific, highly effective defense mech- dysfunction, whether acute or chronic. Common physiology of the digestive system is the marked differ-
anisms exist in each organ to prevent disease. The gut’s digestive disorders affecting 15% to 20% of the U.S. ence in the prevalence of disorders in men and women.
microbiome develops shortly after birth and grows to a population include functional bowel disturbances, gas- Eosinophilic esophagitis, esophageal adenocarcinoma,
point of containing 10 trillion organisms, or nearly 10 troesophageal reflux disease, peptic ulcer disease, hepa- and hepatocellular carcinoma are much more common
times as many cells as the rest of the body! Other titis, gallbladder stones, and infectious diseases of the in men, and irritable bowel syndrome and gallstone
important defense mechanisms with unique actions in stomach and intestines. These and other gastrointesti- disease are much more common in women.

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 43

Plate 1-43  Upper Digestive Tract: PART I

Thalamus

Overview of Control Posterior Hypothalamus Abdominal
Mechanisms (dorsal) (red = sympathetic part, aorta
nucleus of blue = parasympathetic part)
The digestive system is controlled by a fascinatingly vagus nerve
complex interaction between extrinsic and intrinsic Vagus nerve (X)
hormones, the extrinsic and intrinsic nervous systems, Myelencephalon
and a unique electrical control system. Recent increases (medulla Sympathetic trunk Celiac
in our understanding of the neural and hormonal regu- oblongata) ganglia
latory systems have shown that many of the neurotrans- Celiac
mitters crucial to functioning of the CNS are also found Spinal Rami White trunk
in the gut. In fact, many were first identified in the gut sensory communicantes Gray
and then shown to also exist in other organs, including (dorsal root)
the brain. ganglion T9 Thoracic Greater
ELECTRICAL CONTROL SYSTEM splanchnic Lesser
Effective, well-organized contractions throughout the nerves Least Superior mesen-
tubular digestive system are of critical importance to teric ganglion
digestion and absorption in the mixing and propelling T10
of intraluminal contents. As in other muscles, contrac-
tions result from cell membrane depolarizations that T11 Aorticorenal
are recorded as action potentials. These membrane ganglion
changes are responsible for effective electromechanical Thoraco- T12 Intermesenteric
coupling by opening calcium channels that stimulate lumbar L1 (aortic) plexus
actin-myosin interactions. To cause coordinated, circu- spinal L2 Inferior
lar contractions that will effectively move luminal cord mesenteric
contents, these depolarizations must occur around the ganglion
lumen. This is made possible by an electrical syncytium
that preferentially creates simultaneous depolarizations L3 Lumbar Superior
around the lumen. Depolarizations occur in a rhythmic splanchnic hypogastric
fashion from electrical pacemaker potentials created by L4 nerves plexus
the interstitial cells of Cajal. These paced depolariza- L5 Sacral
tions, which facilitate coordinated contractions around splanchnic Hypogastric
the lumen, are known as slow waves. They are not seen S1 nerves nerves
in the esophagus or fundus of the stomach but first Inferior
develop in the upper body of the stomach at a frequency Sacral S2 hypogastric
of three cycles per minute. Gastric paced slow waves spinal S3 (pelvic) plexus
progress down the stomach and end at the pyloric cord
sphincter. In the small intestine, the rate of slow waves
created by the pacemakers is higher in the duodenum S4
(17 to 18 cycles per minute) than the jejunum and even Pelvic splanchnic nerves
slower in the ileum (14 to 16 cycles per minute). This
gradient of slow wave frequency contributes to the Pudendal nerve
proximal to distal movement of luminal contents. The
progressive movement of slow waves from the proximal EXTRINSIC ENDOCRINE SYSTEM Corticotropin-releasing hormone has a major role
to the distal lumen also permits peristalsis to occur in Extrinsic hormones that have a broad influence on in the physiologic response to stress. Levels of this
a caudal direction. Slow wave frequencies in the colon all organ systems also affect the gut; they include hypothalamic hormone increase during actual stressful
are more complex and less uniform but are generally thyroid hormones, adrenocorticotropic hormone, cor- events, as when a person is facing a traumatic situation,
thought to occur at three to six cycles per minute. ticosteroids, mineralocorticoids, corticotropin-releasing but also during events that are not inherently stressful
factor, and leptin. Leptin is a CNS hormone that has a but are perceives as stressful. The latter situation leads
Slow waves result in forceful mixing or peristaltic primary role in influencing digestion by reducing food to challenges in diagnosing and managing functional
contractions only in the presence of stimuli that result intake and modulating the metabolism of nutrients. bowel disorders.
in further cell membrane depolarizations that create an The complex role of hormones in the regulation of
action potential. The presence of an electrical syncy- appetite and satiety is discussed in Plates 1-56 and 1-57. EXTRINSIC NERVOUS SYSTEM
tium favoring circular depolarizations around the Both deficiencies and excesses of thyroid hormones may The previous theory that digestive system functions
lumen permits a circular contraction to be produced lead to gut malfunction. Patients with hypothyroidism are primarily regulated by the autonomic nervous
from the stimulus that creates the action potential. often complain of constipation and loss of appetite. If system and, thus, the CNS is overly simplistic. The
Thus, slow waves control spatial relationships and the disorder progresses to myxedema, motility dysfunc- influence of the autonomic nervous system is mediated
directions of movement of gastric and intestinal luminal tion can develop throughout the digestive system, with by a balance of the stimulatory effects of the para-
contractions that were created by action potentials impaired peristalsis and contractility. sympathetic nervous system and inhibitory effects of
that created electrical responses. Action potential stim-
ulation may originate from extrinsic hormones, extrin-
sic neurotransmitters, intrinsic hormones, or intrinsic
neurotransmitters.

44 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 1-44  Overview of Upper Digestive Tract

Sympathetic efferents disorders in patients plagued by anxiety and hypervigi-
Parasympathetic efferents lance. Increased sympathetic tone during stress associ-
ated with trauma or sepsis is needed to maintain the
Somatic efferents blood pressure and circulation but often results in a
Afferents and CNS connections severe reduction in gut blood flow known as a mesenteric
steal. Decreased blood flow reduces metabolic support
Indefinite paths for the intrinsic protective mechanisms of the stomach,
resulting in unopposed acid injury and severe, at times
Gastric even hemorrhagic, gastritis.
pacemaker Enteric Nervous System
The amazing expansion of our understanding of the
T12, L1 T9 (8) intrinsic or enteric nervous system, both experimentally
T9, 10 L1, 2 and clinically, indicates that the complexity of the
system is similar to that of the CNS. The predominance
T10–12 T10 (11) of the enteric nervous system can be best appreciated
by observing the successful function of liver, pancreatic,
T10–12 Chief segmental sources of small bowel, and even colon transplants in the absence
sympathetic fibers innervating of neural input from the CNS. The enteric nervous
L1, 2 different regions of intestinal system is so crucial for digestion that a separate section
tract are indicated. Numerous is dedicated to its description (see Plate 1-46).
Superior rectal artery and nerves Levator afferent fibers are carried
Rectal plexus ani muscle centripetally through INTRINSIC ENDOCRINE SYSTEM
External anal approximately the same The field of endocrinology was conceived when the first
Inferior anal (rectal) nerve sphincter muscle sympathetic splanchnic hormone, secretin, a major hormone in the digestive
nerves that transmit system, was discovered in 1914. Our knowledge of the
preganglionic fibers. digestive system’s intrinsic endocrine system’s transmit-
ters, functions, and molecular processing has grown
Overview of Control lateral column to splanchnic nerves originating from exponentially since then. Gut hormones stimulate the
Mechanisms (Continued) T2 to L3. These then innervate the gut via nerves coordination of widely diverse functions in each of the
whose bodies are in the celiac, superior mesenteric, or digestive organs to work in concert to digest and absorb
adrenergic neurons in the sympathetic nervous system. inferior mesenteric ganglia. food. Gut hormones achieve this by modifying secre-
Only 10% to 20% of vagal nerves are efferent, far too tion, absorption, motility, and metabolism.
few to control the many complex responses of the seven The autonomic nervous system primarily serves to
digestive organs, much less all the other visceral organs. modify local gut reflexes, but it also plays a critical role Gut hormones alter metabolism not only in the
Direct input to gut functions by the autonomic nervous in a variety of gut reflexes and in communicating affer- digestive system but throughout the body. Insulin
system is important, but the system serves as the ent information to the brain. Medications that inhibit released from pancreatic islet cells is the best example
primary control system only in the striated muscle cholinergic neurons are a cornerstone of treatment of of this important role of gut hormones. Other gut hor-
regions of the pharynx and upper esophagus via cranial spastic disorders of the entire gastrointestinal tract. mones that have a major role in modifying metabolism
nerves and in the rectum and anal sphincter via sacral Anticholinergics are also widely used to reduce oral include glucagon, cholecystokinin, peptide YY, insulin-
and pelvic nerves. Sympathetic nerves reach the gut to secretions during endoscopy, oral surgery, or anesthe- like growth factor 1, and ghrelin. Ghrelin is a hormone
mediate blood flow and help to “shut down” the gut siology. The importance of vagal stimulation of gastric released from the stomach and proximal small bowel
during the fight-or-flight response via the intermedio- secretions explains why surgical selective vagotomy is that increases food intake.
sometimes used to manage complex ulcer disease.
Many gut hormones influence gastrointestinal
The sympathetic nervous system’s fight-or-flight motility. Cholecystokinin and secretin coordinate the
reflex leads to diarrhea and contributes to functional response to food intake by altering gastric emptying,
duodenal contractions, gallbladder contractions, and
contractions of the sphincter of Oddi (relaxed) and
pyloric sphincter (contractions). Perhaps the most fas-
cinating physiologic event of the digestive system is
coordinated emptying of the upper digestive tract
during fasting. This occurs when forceful contractions
of phase III of the interdigestive motor complex, known as
the intestinal housekeeper, are initiated by the hormone
motilin.

Well-defined clinical syndromes have been recog-
nized that are due to neuroendocrine tumors. Advances
in technology have led to the recognition that such
hormone-secreting tumors are more common than pre-
viously appreciated. These important hormone regula-
tors of gut function and the disorders for which they
are known to be responsible are discussed in Plate 1-49.

It can readily be appreciated that the digestive sys-
tem’s seven organs are regulated by a complex interac-
tion of the extrinsic nervous system and extrinsic
hormonal system which modulates the more reflexive
“hard-wired” reflexes of the enteric nervous system and
intrinsic hormonal system. The clinician’s challenge is
to determine which of these mechanisms is at play in
causing a patient’s symptoms and disease.

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 45

Plate 1-45  Upper Digestive Tract: PART I

Brain-Gut Interactions and Via parasympathetic Viscerosensory V
Visceral Reflexes Vague sensory
disturbances about VII
The similarities in neurotransmitters in the gut and head and teeth, or IX
CNS further stimulated our understanding of the actual headache
interactions of the brain and gut. Since the time of Visceroglandular X
Pavlov and Komarov and their colleagues, reflexes Salivation
between the brain and gut and within the gut have been Phrenic nerve Medulla
shown to control much of normal physiology and Viscerovascular
pathophysiology. Visceral reflexes explain a number of Dilatation of Vagus Cervical
clinical signs, many of which are controlled by complex glandular vessels nerve cord
interactions mediated by spinal or CNS pathways. Such
vagal or sympathetic reflexes initiate patterned behav- Visceromuscular ?
iors that often involve multiple organs. Such reflexive Pharyngeal and
responses stimulated by extrinsic neurons are then laryngeal Spinal nerve
mediated locally by enteric neural pathways or intrinsic constriction
hormones. Via sympathetic Sympathetic Thoracic
Viscerovisceral ganglionic cord
One of the most important and well-studied brain- Alterations in cardiac trunk
gut reflexes is the one associated with the control of rate and/or rhythm Key
gastric and pancreatic secretion. Sights, smells, sounds, Prevertebral Parasympathetic
and even the anticipation of food serve as external cues Visceromuscular ganglion Sympathetic
that can stimulate vagally mediated reflexes. Perhaps Contraction of Somatic
the best known is the reflexive increase in acid secretion diaphragm and Enteric Afferents and
that prepares the stomach to begin digestion. These vomiting hormones connectors
reflexes are both instinctive and learned. Although it is Enteric hormone
initiated as an autonomic nervous system vagal reflex, Viscerosensory
the release of acid is ultimately mediated by complex Via parasympathetic Hyperalgesia in skin Initiation Sacral cord
interactions of histamine released from enteroendo- of corresponding of reflex
crine cells and the systemic release of gastrin. Excess dermatome
stress is known to cause gastric upset. Such stress is Pelvic splanchnic nerves
often attributed to “nerves” and dismissed, but it may Viscerovascular
be an important cause of disease, including peptic Segmental
ulcers, as described by Cushing. For example, the vasodilatation,
incidence of perforating gastric and duodenal ulcers warmth of skin,
increased markedly in England during the bombings of dermographism
World War II.
Visceromuscular
Another very important visceral reflex is the gastro- Rigidity of muscles
colic reflex. This normal physiologic response of post- of corresponding
prandial emptying of the colon occurs gradually as a segment or
meal is consumed and colonic contractility increases myotome; erection
progressively over the next 30 to 60 minutes. The reflex of hairs, goose
is initiated by specific receptors in the duodenum that flesh (pilomotor)
respond to the intake of fatty acids but not liquid alone
or nonessential amino acids. Patients who suffer from Viscerovisceral
irritable bowel syndrome have an exaggerated gastro- Altered secretion,
colic reflex. Colonic contractility is not only more tonus, and motility
forceful but begins sooner than normal. Spastic con- in organs of
tractions occur shortly after a meal is ingested and often corresponding or
peak in intensity before the meal is complete, causing related spinal
diarrhea, cramping pain, and/or bloating. In this cen- segments
trally initiated reflex, local serotonergic neurons in the
myenteric plexus stimulate propulsive and spastic con- Viscerovisceral
tractions that at one time may lead to constipation and Altered motility in
at another, diarrhea. Afferent impulses from the hyper- viscera of other
contractile and often distended sigmoid colon initiate spinal segments
reflexes to the CNS (e.g., headache, a strange feeling (gastro-ileal,
in the head), to the bronchial tree (difficulty in breath- gastrocolic,
ing), to the stomach (epigastric distress, indigestion), duodeno-ileal,
and to the abdominal skin (intolerance of constricting duodenocolic,
garments). appendicogastric
reflexes, etc.)

The afferent limb of viscerosomatic reflexes originates Unusual and often dangerous viscerosomatic or vis-
from gut viscera and then affects other visceral and cerovisceral reflexes are commonly encountered. Gas-
somatic structures; it may involve sympathetic or para- trointestinal disorders leading to vasovagal reflexes
sympathetic nerves. The efferent limb is usually via often lead to syncope in the setting of severe abdominal
parasympathetic nerves. The viscerosensory reflexes pain, extremes of nausea, exposure to particularly
result from shared afferent pathways where C fibers in noxious substances, and severe diarrhea. In such
the dorsal horn that are not myelinated from visceral settings, visceral “brain-gut” stimuli initiate vagally
organs comingle with somatic afferents in the dorsal mediated hypotension, bradycardia, and diaphoresis.
horn or spinal column. They explain the phenomena of Swallowing syncope, a related reflex, occurs when a
“referred pain” and of “skin hyperalgesia,” which, in the patient experiences an esophageal spasm, irritation, or
case of sympathetic reflexes, occurs in skin areas (der- distention that leads to vagally induced arrhythmias or
matomes) innervated by the same spinal segment from bradycardia and syncope. Gastroesophageal reflux can
which the nerve supply of the diseased viscus is derived. rarely lead to a similar reflex.

46 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 1-46  Overview of Upper Digestive Tract

Enteric Nervous System Subserous
plexus
The digestive system’s enteric nervous system is by far Longitudinal
the largest neural network outside of the CNS and intramuscular
contains more neurons than the spinal column. The plexus
variety of neurotransmitters is similar to that in the
CNS. The complexity with which these transmitters Myenteric Myenteric plexus Multipolar neurons,
interact is fascinating and intricate. This system pro- (Auerbach) (guinea pig, Champy- type II, in myenteric
vides the local “hard wiring” for all local gut reflexes, plexus Coujard, osmic stain, plexus (cat, Bielschowsky,
most notably peristalsis. Local responses are modulated Circular ϫ 20) silver stain, ϫ 200)
by input from the other regulatory systems (extrinsic intramuscular
hormones, intrinsic hormones, parasympathetic and plexus
sympathetic nerves from the autonomic nervous system,
and other enteric nerves). Submucosal
(Meissner)
The bodies of neurons in the enteric nervous system plexus
are located in two layers in the gut, the Auerbach sub-
mucosal plexus and the Meissner myenteric plexus. The Periglandular
Auerbach plexus is located on the luminal side of the plexus
circular muscle and has sensory neurons, effector
neurons, and interneurons. The simplest description of Submucous plexus Human myenteric plexus
its function is that its neurons serve primarily to inte- (guinea pig, stained by with VIP immunoreactive
grate events and conditions in the lumen with the Golgi impregnation, ϫ 20) neurons
motility functions of the muscularis mucosa and the
secretory and vascular functions of the submucosa. It is Hormone Cell type and location Hormone Cell type and location
important to add, however, that reflexes have been
identified from the submucosal nerves to the myenteric EPGF Enteric neurons Secretin-glucagon
nerves that mediate peristalsis as well as to sensory sites Epidermal growth factor Secretin S cells in proximal small bowel
in the dorsal root ganglia and mesenteric ganglia. For GLP-1&2 L cells in small intestine and B
example, light mucosal stimulation alters the peristaltic Gastrin-cholecystokinin cells of pancreatic islets
reflex via enteric nerves in the mucosa to the submuco- Gastrin G cells in gastric antrum VIP Enteric neurons
sal ganglia and to extramural ganglia in the mesentery CCK I cells in proximal small Glucagon A cells in pancreatic islets
and paraspinal ganglia. GHRH Enteric neurons
Ghrelin bowel PACAP Enteric neurons and
It is similarly reasonable to view the myenteric plexus Motilin M cells in proximal small pancreatic islets
as having the primary function of integrating all local Pancreatic polypeptide Pancreatic islet cells
reflexes, including local contractions and peristalsis, as intestine Orexin Smooth muscle, mucosa; Both
well as the blood flow needed to perform these func-
tions. For example, although most motor neurons are Growth factors enteric plexuses and hypo-
very short, interneurons containing serotonin travel Transforming growth factor thalamus
several centimeters to integrate the peristaltic reflex.
Insulin Somatostatin D cells in stomach, intestines
The neurotransmitters in the two intrinsic plexuses Insulin-like growth factor B cells in pancreatic islets Somatostatin and pancreas
are incredible in number and complexity. Enteric Ghrelin
neurons are characterized by their morphology and Pancreatic polypeptide L cells in ileum X/A –like endocrine cells in
neurotransmitter content. Over 30 neuropeptides have Peptide YY Sympathetic neurons stomach
been identified and sequenced. These transmitters are Neuropeptide Y Enteric neurons
grouped in families based on similarities in amino acid Substance P Tachykinin Enteric neurons
sequences. Although an encyclopedic summary is inap- Neurokinins
propriate for this chapter, a brief listing of well-defined
neurotransmitter families found in the enteric nervous tides, especially NK-1 (substance P and substance K), nervous system it can function as a transmitter in
system of the digestive system is shown. Regrettably, are often shown to be stimulating motor neurons. In interneurons. Calcitonin gene–related peptide is most
the names initially assigned to these transmitters often contrast, vasoactive intestinal peptide is invariably an commonly seen as a transmitter in afferent neurons,
had little to do with the primary functions that they inhibitory motor neuron, often colocalized with nitric especially those seen to reach the esophageal or intes-
were later found to perform. Furthermore, the list of oxide. Somatostatin also inhibits many gastrointestinal tinal lumen.
functions that are influenced by each transmitter belies functions, including absorption, secretion, and blood
any effort at simplification. An anatomic factor that flow. Neuropeptide Y is found throughout the digestive The role of the enteric nervous system, with its
prevents an oversimplification of the role of these trans- tract colocalized with sympathetic transmitters such as highly diverse neurons and complex array of interacting
mitters is the demonstration that a single neuron may norepinephrine. Gastrin-releasing peptide not only neurotransmitters, emphasizes how incredibly fine-
contain more than one neurotransmitter. Colocaliza- stimulates the release of gastrin, but within the enteric tuned and integrated are the local reflexes of gut motil-
tion of neurotransmitters occurs across different classes ity, secretion, absorption, and circulation.
of transmitters, including peptidergic and nonpeptide
transmitters, most notably nitric oxide. The incredibly
complex, specific influence these nerves have on func-
tions has been further demonstrated by the fact that in
response to various stimuli, there may be selective
release of colocalized transmitters from a single neuron.

Characterization of transmitters as having specific
functions risks oversimplification because the transmit-
ters may have different effects depending on the cell of
origin. Some common patterns have been noted,
however. The tachykinin-neurokinin family of pep-

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 47

Plate 1-47  Upper Digestive Tract: PART I

VISCERAL REFERRED PAIN

Referred pain

Interpretation of Visceral Duodenum, Liver, gallbladder, and Gallbladder
Pain head of duodenum (irritation of Liver
pancreas
Pain is one of the most important clues to the presence Gallbladder diaphragm) Pancreatic
of a disorder in the digestive system. After upper respi- Stomach pain
ratory infections, abdominal pain is the second most Liver Spleen
common cause of absenteeism from work or school. Of Small Factors influencing seeking
the four cardinal presentations of illness of the digestive intestine healthcare
system (pain, bleeding, obstruction, and perforation),
pain may be the most challenging to interpret. Under- Kidney and
standing the physiology and pathophysiology of visceral ureter
nociception is essential to developing a well-conceived
approach to understanding and diagnosing pain in all Cecum and Sigmoid colon
of the visceral organs of the abdomen and chest. The ascending colon
first step in interpreting the patient’s experience of pain
is to characterize its severity, associations, consistency, Determinants of healthcare seeking behavior
duration, and location. Pain associated with swallowing,
eating specific foods, or defecation but not with exercise Pathologic processes Clinical manifestations
is most likely emanating from the digestive system.
•Tissue injury •Chest pain •Education
Pain is often the most important issue for the patient. •Hiatal hernia •Distension •Anxiety
Assessing its severity is highly subjective; the clinician •Reflux •Dysphagia •Social factors
must distinguish pain associated with functional disor- •Increased acid •Bleeding •Abuse history
ders from that associated with life-threatening disor- •Erosions •Access to care
ders. The severity of pain may be similar in both exposure •Obstruction •Sleep deprivation
circumstances. Pain should be described on a scale of 1 •Impaired clearance
to 10, with 1 being minor discomfort and 10 being the •Impaired mucosal
most severe pain the patient has ever experienced.
Unfortunately, the intensity of pain does not correlate resistance
well with the severity of an underlying disorder. For •Dysbiosis and nerve
example, patients with esophageal reflux but normal
endoscopic findings often experience more severe pain activation
than patients with erosive esophagitis, strictures, or
even Barrett esophagus, a premalignant condition of logic factors. At the same time, it is important to appre- determine if it has changed. Pain that is variable and
the esophagus. Furthermore, functional pain is often ciate that dismissing patient symptoms as “functional” inconsistent in its location, severity, or associations sug-
characterized by the patient as unbearable because of all too often leads to missing rare diagnoses such as gests a functional pathophysiology. Pain that is severe
the patient’s hypervigilance to the digestive system. malabsorption, preventable food reactions or allergies, in the daytime and at times of stress but absent at night
Some patients ignore early signs of abdominal discom- porphyria, vasculitis, or Crohn disease. For example, for is also more likely functional. In some conditions,
fort only to later discover that they were due to impend- many years, pain was often attributed to the common the perceived movement of pain may help to localize
ing obstruction from a severe inflammatory or malignant functional bowel problem of irritable bowel syndrome; the source, particularly if the pain is intensifying. The
disorder. Encouraging patients to achieve the right now, however, we can easily diagnose the cause of such classic example of this is acute appendicitis. This acute
balance between paying attention to the body’s mes- pain as small intestinal bacterial overgrowth, lactose abdominal emergency often begins with vague pain
sages and ignoring or denying painful signals from the or other disaccharide malabsorption problems, celiac across the abdomen or in the periumbilical region.
gut can be a key to helping them achieve good health. disease, or nonceliac gluten sensitivity. When the peritoneum becomes inflamed, the location
becomes clearer and usually ends in a point of tender-
Functional pain has been defined as the presence of Localization of pain is also important. Unfortunately, ness in the right lower quadrant over the affected
disordered gastrointestinal function despite a normal localization can be very challenging for the patient organ known as the McBurney point (one third of the
gross appearance and anatomy and normal initial blood because of the physiology of visceral nociception. distance from the anterior superior iliac spine to the
test results. Functional pain is not indicative of a weak When taking the medical history, the clinician should umbilicus).
character or weak countenance, nor is it imaginary pain, try to identify the location of the pain at its onset and
falsified pain, or malingering. Clarifying that these
symptoms are “real” is more difficult for functional pain
due to muscle spasms or to subclinical injury such as
esophageal spasm, nonerosive esophageal reflux, non-
ulcer dyspepsia, biliary dyskinesia, or irritable bowel
syndrome, which are characterized by motility disor-
ders that are rarely identified on motility testing, much
less on endoscopic or radiologic findings. Diagnosing
these and other functional disorders may be attempted
as “diagnoses of exclusion.” Such attempts are unac-
ceptable for any physician who hopes to keep unneces-
sary health care expenditures at a minimum.

The severity of pain is influenced by a variety of
nonorganic issues, including the patient’s psychological
state, previous experiences, educational level, and socio-

48 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 1-48  Overview of Upper Digestive Tract

Gray rami communicantes Superior cervical ganglion

Sublingual gland

Interpretation of Visceral Innervation to arrector pili C1– C8 Submandibular gland
Pain (Continued) muscles, vascular smooth
muscle, and sweat glands First thoracic Stomach
The most likely source of abdominal pain is often of skin ganglion
suggested by a careful history and physical examination. Liver
Four regions should be considered. Determining which Greater Gallbladder
side the pain is on is also helpful, but even cholecystitis splanchnic Bile ducts
and appendicitis may present with left-sided pain. Limi- nerve Pancreas
tation in the ability of the history and physical examina-
tion to localize the source of visceral pain is in stark Celiac Suprarenal gland
contrast to somatic pain, which can usually be pin- ganglion
pointed to within a few millimeters. These limitations
are due to the anatomic and physiologic distinctions T1– T12 Lesser splanchnic Kidneys
between the visceral and somatic nervous systems. nerve

Visceral receptors cannot distinguish the cause of the White ramus Aorticorenal Intestines
pain as inflammation, ischemia, malignant or infectious communicans ganglion
invasion, or distention (the commonest cause). At the Gray ramus Least splanchnic nerve
level of a receptor, somatic sensation can rely on a host communicans
of distinct receptor types of high density in the skin and Superior mesenteric
in striated muscles innervated by the CNS. In contrast, First lumbar ganglion ganglion
afferent receptors in viscera are sparse and most are
naked nerve endings that respond to a variety of stimuli Lumbar splanchnic nerves
(polymodal). Receptors that are often useful in local- Inferior mesenteric ganglion
izing pain are in muscle spindles in the muscularis
propria or encapsulated pacinian corpuscles in the L1– L5
mesentery.
Superior Sacral Descending
Another factor commonly leading to confusion hypogastric plexus splanchnic colon
regarding gastrointestinal symptoms is the tendency of nerves Sigmoid colon
a patient to adapt to chronic and persistent stimuli. First sacral
Instead of increasing feedback to the CNS, persistent ganglion S1– S5 Rectum Inferior
stimulation of gut receptors gradually leads to a dis­ Urinary hypogastric
tinguished signal output over time. The frequency with bladder plexus
which these and other receptors discharge electrical
currents gradually decreases over time when a stimulus Preganglionic fibers External genitalia Prostate
is persistent. Adaptation may be dangerous when the Postganglionic fibers
body no longer recognizes a signal of severe distention
from obstipation or invasion from a malignancy. Thoracic Lumbar Sacral
1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 1234
Nerves carrying afferent information do so through Esophagus (lower)
unmyelinated C-type fibers. The nerves may be in the Stomach
vagus nerves, in which 80% of the fibers are afferent Liver, gallbladder
and which terminate in the nodose ganglion. Others Pancreas
travel in the sympathetic system through the dorsal root Small intestine
ganglia from splanchnic nerves (20% afferent) or pelvic Colon, rectum
nerves (50% afferent). Afferent signals travel to the Kidney, ureter
spinal column in nerves that coalesce with somatic Urinary bladder
nerves in the dorsal horn. This sets up a relationship Ovary, fallopian tube
between visceral and somatic structures that may create
unusual radiation patterns to the musculoskeletal Uterus
system known as referred pain. Examples of visceroso- Cervix
matic convergence leading to referred pain are gallblad- Testicle, epididymis
der and liver pain to the right shoulder, esophageal and
cardiac pain to the left arm, and kidney pain to the (From Klein KB, Mellinkoff SM. Approach to the patient with abdominal pain. In: Yamada T, ed.
perineum or scrotum. Within the dorsal roots, nerve Textbook of Gastroenterology. Philadelphia: Lippincott Williams & Wilkins, 1991, 660-681.)
signals may be transmitted to the CNS bilaterally, a fact
that explains why visceral pain is often poorly localized splanchnic from the colon and appendix, as well as the cord. Afferent nerve input to the spinothalamic sensory
to one side of the body or the other. kidney, ureters, urinary bladder, ovaries, and uterus, pathways may be disrupted by inhibitory signals
through T11-T12. Overlap occurs again at the level of descending from the frontal cortex. This phenomenon
Perhaps the most significant limitation of visceral the splanchnic nerves, which innervate multiple organs, can be helpful in a situation in which a patient needs to
pain is the fact that afferents from each organ enter the including the cervix, testicles, epididymis, sigmoid, and ignore pain to be able to continue to function. This
spinal column through splanchnic nerves at multiple rectum, through T11-L1. This convergence of afferent reflex is similar to the gate theory for exceptional somatic
levels, with multiple other organs. The phrenic nerve fields makes it difficult for the patient, much less the nerve and muscle function in times of pain or excep-
therefore carries afferent information from the liver clinician, to identify the source of the pain. The conver- tional need. Such pathways can become maladaptive,
capsule, spleen, and diaphragm through C3-C5; the gent fields obviate the possibility of a viscerotopic distri- however, when a patient uses them to suppress impor-
greater splanchnic from many upper gastrointestinal bution of visceral afferents in the brain, as occurs so tant information that should result in seeking medical
organs, including the gallbladder, stomach, pancreas, precisely for somatic nerves. Only the pharynx and care for pathologic symptoms.
and small intestine, through T6-T9; and the lesser esophagus show any clear viscerotopic pattern. This
pattern of distribution occurs within the brainstem near In summary, visceral pain is a subjective symptom of
the swallowing centers. great clinical significance that can only be interpreted
using a biopsychosocial model rather than a strict
Pain perception may be altered at the level of the medical model and must take into account the many
spinal cord by inhibitory input from the CNS or spinal limitations of visceral nociception.

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 49

Plate 1-49  Upper Digestive Tract: PART I

Clinically important peptide hormones and associated disease states

Peptide Disease state Clinical correlations

Gastrin Zollinger-Ellison syndrome – severe Pentagastrin (analogue) used to assess
peptic ulcer disease, diarrhea acid secretory capacity and provoke
bioactive neuropeptide secretion in
Gastrointestinal Hormones VIPoma and medullary carcinoma of the
thyroid
The scientific field of endocrinology began with the
discovery of secretin in 1904 by Starling. Since then Cholecystokinin Abnormalities seen in bulimia, celiac Dynamic gallbladder emptying HIDA
it has been shown that an incredibly diverse list of disease, delayed gastric emptying scan study to evaluate gallbladder
digestive tract functions are influenced by a variety contractility in chronic cholecystitis and
of gastrointestinal hormones. Specific functions of sphincter of Oddi manometry for biliary
gastrointestinal hormones and their respective disor- dyskinesia
ders will be discussed in greater detail in chapters on
specific organs. A brief outline of major gut hormones VIP Verner-Morrison syndrome (VIPoma) – VIP-based radionuclide imaging used to
follows, as well as a tabulation of major digestive tract voluminous diarrhea, hypokalemia, locate and guide resection of VIP-
hormones. flushing absent in Hirschsprung disease, secreting tumors, pancreatic adeno-
achalasia carcinomas, and carcinoid tumors that
The hormones of the gastrointestinal tract are express VIP receptors
released by three mechanisms. Endocrine cells of the
pancreas congregate in Langerhans islets that are inter- Secretin Found in neuroendocrine tumors (NETs), Used to assess exocrine pancreatic
mingled with groups of exocrine cells in the acini and but despite being a potent stimulant of function; secretin stimulation test used to
in the ducts. There they release a variety of hormones pancreatic secretion, isolated syndrome diagnose gastrinomas; aids in cannulation
into the adjacent capillaries. In contrast, most endo- has not been described of pancreatic duct during ERCP
crine cells in the digestive system are unlike those in
other hormone-secreting organs of the endocrine Somatostatin Somatostatinoma – diabetes, diarrhea, Octreotide (analog of SN):
system which are localized to specific organelles in an gallstone disease, migratory necrolytic • Diagnostics – Diagnosis and locali-
organ or make up an entire gland. Enterochromaffin erythema zation of neuroendocrine tumors
cells containing peptide hormones and nonpeptide • Therapeutics - Secretory diarrheas,
transmitters are interspersed between other epithelial variceal bleeding, certain neuroendo-
cells along the surface of the mucosa throughout the crine tumors
stomach and intestines. The apical border of these spe-
cialized cells reaches into the lumen, where microvilli Motilin Not described Macrolide antibiotics (erythromycin)
can react to changes in the chemical concentration of stimulate motilin receptors and are used
intraluminal contents. Gastrointestinal hormones are in diabetic gastroparesis; also used to
released from these epithelial cells by three different clear gastric contents and increase
modalities: (1) They may be released into the local visibility in emergency endoscopy for
capillaries and thus into the systemic vascular system in upper gastrointestinal bleed
a typical endocrine fashion, as occurs in the pancreas;
hormones released in this endocrine fashion influence Types of cellular communication in gastric secretion
other digestive tract functions, the blood flow, or the Gastrin
appetite in response to specific stimuli to the mucosa.
(2) Other endocrine cells release their hormones locally, ϩ ϩ HCI
through specific organelles that release directly onto Gastrin HCI Ϫ
nearby cells in a paracrine fashion. (3) Hormones may be
released into the interstitial space in a less specific exo- Gastrin Somato-
crine manner. Through these highly specialized mecha- statin
nisms, hormones are released systemically, locally, or
specifically onto nearby targeted cells. ϩ Endocrine secretion involves Paracrine secretion involves
Neurocrine stimulation secretion of transmitters into secretion of transmitters
Isolation, sequencing, and molecular analysis of or inhibition acts via circulation for transport into intercellular spaces
intracellular messaging systems that modify the release neuropeptides directly to target cell with migration to target cell
of gastrointestinal hormones have revealed just how on target cell
complex the regulation of these mediators are as they
influence gut function. A common feature of gastroin- drome multiple endocrine neoplasia, which is due to a Increased understanding of gastrointestinal hor-
testinal hormones is the complex way in which they are mutation of the MEN-1 gene which encodes a cyclin- mones has led to a variety of diagnostic and therapeutic
synthesized and processed posttranslationally. The hor- dependent kinase inhibitor. This autosomal dominant uses for them. One of the most valuable tools for
mones are typically derived from a large pretransla- syndrome is associated with tumors of the islet cells localizing and evaluating neuroendocrine tumors is a
tional messenger RNA that may contain more than one of the pancreas, parathyroid glands, and pituitary gland. 111indium-labeled radioactive modification of the soma-
hormone sequence. The translational products of these It may also be associated with tumors of the adrenal tostatin molecule in the “octreotide scan” (somatostatin
mRNA messages are long peptide chains of prohor- cortex, carcinoid tumors, and nonendocrine tumors, receptor scintigraphy). Modified somatostatin is also
mones or prehormones. Posttranslationally they are including angiofibromas, leiomyomas, collagenomas, used to treat upper gastrointestinal bleeding from
cleaved into hormones of varying lengths, each of lipomas, and meningiomas. esophageal varices.
which has a different affinity for its receptor ligand
(e.g., gastrin may circulate as big-gastrin 36, gastrin 34,
or a smaller version of gastrin-8).

Neuroendocrine cells can grow into tumors that may
result in complex, often characteristic clinical syn-
dromes. These symptomatic neuroendocrine tumors
may occur sporadically or as part of the inherited syn-

50 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 1-50  Overview of Upper Digestive Tract
MUCOSAL DEFENSE MECHANISMS

H+

Pepsinogen

Overview of Protective Mucus HCO3Ϫ H+ Mucus-
Mechanisms Rapid bicarbonate
cell barrier
Many normal physiologic functions necessary for turnover Intercellular
breakdown and processing of ingested nutrients also tight
pose a potential risk to health. These include the junctions
normal mechanical forces associated with gastrointesti-
nal motility, extreme acidic content of the stomach, the HCO3Ϫ
potent enzymes secreted by the pancreas and intestinal
epithelium, the caustic nature of bile salts, and the tril- H+
lions of intraluminal microorganisms. The digestive
system must also have protection from ingested sub- HCO3Ϫ
stances that pose a risk to mucosal integrity and health.
Even without gross disruption of the integrity of the Gastric mucosa and submucosa protected from chemical injury by mucus-bicarbonate surface barrier
luminal organs, as occurs with penetrating wound that neutralizes gastric H+ and by epithelial “tight junctions” that prevent H+ access to subepithelial tissue.
injury or disorders that lead to mucosal ulceration or Prostaglandins are important regulators of all these defense factors.
perforation, there is a constant potential for mucosal
invasion at a cellular level. functions and brush-border enzymes and enhancing tion and pulmonary aspiration. The esophageal con-
the diffusion of nutrients in and enzymes out to tractive force moves down the esophagus in less than
The digestive system has incredibly complex and the lumen by reducing stasis, which could result in 10 seconds in a coordinated, single-ring–like peristaltic
intricate immune mechanisms that defend against increased microorganism concentrations and depth of sequence to propel the swallowed bolus into the
microorganisms. These immune systems are extensive the “unstirred water layer” (thus, potentially injurious stomach. Peristalsis creates a stripping wave to propel
and include both systems used by the rest of the body substances are exposed to chemical degradation before the potentially dangerous contents further away from
and systems specific to the digestive tract, including they can induce injury). They also protect the mucosa the airway and below the check-valve function of the
intraepithelial lymphocytes; specialized M cells; immu- by limiting the duration of exposure of mucosal cells to lower esophageal sphincter. When the sphincter com-
noglobulin A (IgA), the gut-associated immunoglobulin potentially injurious agents, including organisms, medi- petence is interrupted, a secondary (nonvoluntary) peri-
submucosal immune cells; and cells outside the diges- cations, and particulate material, that can have mechan- staltic contraction pushes regurgitated gastric contents
tive system, known as gut-associated lymphoid tissue ically injurious properties. away from the airway and pharynx back into the
(GALT) cells. stomach.
Oral, pharyngeal, and upper esophageal sphincter
Epithelial lining cells of the digestive system have relaxation works in an intricately orchestrated way to In the stomach, ingested materials are triturated or
highly specific structures designed to prevent back dif- propel liquids and solids away from the nasal passages ground into smaller particulate matter that can be acted
fusion of intraluminal contents across the epithelium. and larynx to protect against nasopharyngeal regurgita- upon more effectively by digestive secretions. The
These include the ubiquitous secretion of mucus, spe-
cialized apical surface characteristics, and cell-cell adhe-
sion complexes such as tight junctions. The intraluminal
microorganisms pose a great threat, but they also have
a protective benefit (see Plate 1-54). There are also a
host of nonimmune defense mechanisms at play
moment by moment to sustain the integrity of the
digestive system in the hostile environment of a “tube
within a tube.” We will summarize these other nonim-
mune defense mechanisms in this section, including
motility, secretion, and blood flow.

Motility plays an important role in protecting the
digestive tract from damage and in maintaining health.
Propulsive contractions of the muscularis propria occur
in all luminal organs, including peristalsis, migrating
myoelectric complexes (phase III of the interdigestive
motor complex), and mass actions in the colon. Most
contractions are not propulsive but serve to mix the
intraluminal contents and increase their exposure to the
luminal surface to facilitate digestion and absorption.
In the composite picture, however, the net sum of many
propulsive contractions and fewer retrograde contrac-
tions results in a net force propelling luminal contents
in an oral to anal direction. This prevents regurgitation
and limits the accumulation of microorganisms in the
upper gastrointestinal tract. Tonic contractions of the
sphincters also help to maintain the correct flow of
luminal contents. The active mixing and propulsive
contractions of the muscularis mucosa and muscularis
propria enhance digestion by increasing the opportu-
nity for luminal contents to be exposed to absorptive

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 51

Plate 1-51  Upper Digestive Tract: PART I

INTESTINAL HOUSEKEEPER

LES MMC Cycle
Antrum
SI-15

SI-60
SI-140

SI-220 16 min
SI-300
SI-380

SI-460
Phase III of the migrating motor complex. When absent or infrequent, small intestinal bacterial overgrowth can develop.

Overview of Protective in humans. The cycle is interrupted by eating and is cell surface; the gastric lumen pH of 1.0 to 1.5 is pre-
Mechanisms (Continued) initiated through the action of the hormone motilin. vented from injuring the cell.

pyloric sphincter serves a “sieving function” that Secretions can both damage and protect the epithe- Secretion of fluids also provides a protective func-
permits only small particles to pass. This creates a soft lium of the luminal organs. Peristalsis and mixing con- tion. The secretion of electrolytes and accompanying
chyme coated with mucus which can easily pass through tractions of the luminal organs can, however, produce diffusion of water by salivary, gastric, duodenal, pancre-
to the rest of the digestive tract. In so doing it not only incredible forces against the mucosa. To reduce the atic, and gallbladder epithelia dilute ingested nutrients
optimizes the surface area for digestion but further impact of these forces, epithelial cells and submucosal to facilitate digestion and transit. It also provides a
reduces the size of particulates to prevent larger matter glands from the mouth to the anus create a thin layer means of diluting potentially injurious chemicals and
from interfering with digestion or becoming lodged in of slimy substances, including mucins, phospholipids, disperses them for processing by other defense mecha-
the lumen or ileocecal sphincter. and the trefoil-factor family of peptides, which lubricate nisms. Secretion of high concentrations of hydrochloric
the wall and reduce friction. Mucus is synthesized in acid by gastric parietal cells creates a pH of 1.0 to 1.5.
Arguably one of the most complex and fascinating the Golgi apparatus of surface mucus cells and submu- This solution protects the body from potentially injuri-
physiologic activities in the digestive system is the cosal cells and packaged into secretory granules that ous organisms by effectively killing microorganisms
pattern of interdigestive motor complexes that occurs after discharge their contents from the apical surfaces of that are ingested or that grow in the oral or aerodiges-
digestion of a meal. Initially, after the intense contrac- cells. Mucus-secreting cells can also deliver their pro- tive cavities. This environment sterilizes intraluminal
tile activity associated with mixing and propelling nutri- tective substance into the lumen by accumulating large contents in the stomach and duodenum. When acid
ents down the digestive system there is a period of rest. quantities of mucus in their cytoplasm and then exfoli- secretion is decreased by medications or gastric atrophy,
Then, after a brief period of active, mixing (segmental) ating the entire cell into the lumen. there is an increased risk for infection and for small
contractility, the intestinal housekeeper passes from the intestinal bacterial overgrowth. The latter can lead to
gastroesophageal junction to the distal ileum or ileoce- Mucus not only provides a protective effect by lubri- bile salt deconjugation and competition for nutrients,
cal sphincter. This sweeping wave of intense contractil- cation but establishes a diffusion barrier that creates a most notably vitamins such as B12. Digestive enzyme
ity provides a mechanism for clearing the stomach and pH gradient above surface mucus cells that face the and bile salt secretion also reduces the survival of all but
small intestine of any indigestible solids, microorgan- lumen of the stomach or duodenum; it can contain the most resistant microorganisms.
isms, and waste products to prepare it for the next meal. extraordinary concentrations of acid, to a pH of 1.0 to
In so doing, larger particles such as sinew, indigestible 1.5. Although the diffusion barrier of mucus alone is Each of these nonimmune defense mechanisms
food stems, large seeds, or such modern solids as swal- ineffective against the diffusion of protons (hydrogen depends on rich mucosal blood flow to occur. When
lowed gum are retained in the stomach during digestion ions from hydrochloric acid), it can effectively slow the this blood flow is reduced by the ‘mucosal steal’ that
so that they do not interfere with the body’s need to diffusion of the much larger molecules of bicarbonate occurs as a result of hypotension or sympathetic over-
capitalize on all swallowed nutrients, until the house- secreted from the surface mucus cells and glands of the load, the risk for mucosal injury is increased. Regula-
keeper wave propels them as waste into the colon. This stomach. This creates a pH gradient by slowing the tory messengers that enhance mucosal protective
cycle continues in mammals such as dogs every 90 diffusion of the much larger bicarbonate ions away from mechanisms, including blood flow, such as prostaglan-
minutes in a strikingly regular way, but it is less regular the mucosa, where a much safer pH of 7.0 is seen at the dins, are also critical for maintaining mucosal health.

52 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 1-52  Overview of Upper Digestive Tract
GUT IMMUNE SYSTEM

Intraepithelial
lymphocyte

Secretory
sIgA

Goblet cell
M-cell

Dendritic
cell Plasma cell

Immune Defenses of the B- cell
Digestive System T- cell

Peyer patch

It has often been emphasized that the digestive system Capillary
“tube” is the host to a very hostile intraluminal environ-
ment that is actually not part of the organism itself. Macrophage
This tube includes microorganisms and chemicals that
if not kept in check can quickly result in the patient’s role in processing the immune response cascade. This cells (M cells) and their adjacent lymphoid follicles, or
death. It is critical for health that the luminal organs is achieved by a wide variety of lymphocytes, macro- Peyer patches. A Peyer patch is a highly active accumu-
have mechanisms that are highly selective in identifying phages, and dendritic cells found in the lamina propria lation of macrophages, dendritic cells, and T and B
foreign antigens and thus prevent the invasion of of the intestinal organs, and to a lesser extent in the lymphocytes which can evaluate antigens and even
luminal microorganisms through or between epithelial stomach. The esophagus has lymphocytes, but in a whole microorganisms brought across the epithelium
cells into the submucosa, where they can invade the rest normal state has no eosinophils, mast cells, or polymor- through the porous M cells and their adjacent
of the body. This system must also be able to distinguish phonuclear cells. specialized epithelial cells. Submucosal dendritic cells
between harmless commensal organisms and organisms independent of M cells also play a key role as antigen-
that cause disease. The extensive, specialized system of Terminally differentiated B lymphocytes become presenting cells. Once activated, B-cell and T-cell blasts
immune cells that constantly defend against luminal plasma cells in the lamina propria, where they are the can leave the Peyer patch and enter the circulation or
attack with a perpetual state of controlled inflammation major source of IgA. IgA synthesized in the gut can be be carried by the lymphatics to adjacent nodes or to the
described in this section is known as the GALT system. released in monomers into the circulation. IgA is also bloodstream.
If the GALT system is not effective, microorganisms secreted into the lumen of various organs, including the
can invade; if it is overly active, autoimmune disorders gut, as secretory IgA in the form of dimers, which are Another important part of the immune defense
result, such as chronic gastritis, celiac disease, or inflam- two IgA molecules coated with a specialized secretory systems for the digestive system are the large numbers
matory bowel disease. Other defense mechanisms are component that prevents enzymatic digestion. Secreted of lymph nodes found throughout the mesentery and
discussed with Plates 1-50, 1-51, 1-53, and 1-54. IgA dimers are kept near the surface by becoming the larger accumulations of lymph glands at the base
trapped in the mucus glycocalyx. Intraluminal secretory of the three major sources of arterial blood to the gut,
Epithelial cells provide the first line of both mechani- IgA that reaches the distal ileum can be reabsorbed and the celiac, superior mesenteric, and inferior mesenteric
cal and immune defenses. This is possible because the transported to the Kupffer cells of the liver, where arteries.
cells not only have specialized qualities that prevent the antigen can be destroyed and the secretory IgA
fluid and bacterial movement through or between cells, released into the bile, and thus circulated back to the Finally it must be remembered that the liver is second
but they can also process antigenic material and func- intestinal lumen. only to the small intestine as the second largest reticu-
tion as antigen-presenting cells. loendothelial organ in the body. Antigens and microor-
Dispersed between epithelial cells of the small intes- ganisms that escape other gut defenses are carried to
Lymphocytes are the next line of defense in the tine can be found highly integrated antigen-processing the liver, where they can be filtered from the blood by
digestive system. In fact, there are over a trillion structures consisting of modified microfold epithelial sinusoidal Kupffer cells.
immune-active cells in the gut, making it by far the
largest lymphoid organ in the body. A fascinating, dis-
tinct subclass of lymphocytes, the intraepithelial lym-
phocytes, migrate into the intercellular space between
epithelial cells. There they provide an important cyto-
toxic and antiviral line of defense but play little, if any,

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 53

Plate 1-53  Upper Digestive Tract: PART I

H+ MUCOSAL CELLULAR DEFENSE MECHANISMS pH 1.5
Pepsinogen H+

Pepsin

Mucus-bicarbonate pH 2
barrier
Mucus HCO3– + H+ H2O + CO2

(neutralization)

pH 7

Epithelial
tight
junctions

HCO3-

Gap junction

HCO3– H+

Epithelial Cell Defense Gastric mucosa and submucosa protected from chemical injury by mucus-bicarbonate
Mechanisms of the Digestive surface barrier that neutralizes gastric H+ and by epithelial “tight junctions” that prevent
System H+ access to subepithelial tissue

The potential for intraluminal contents to cause severe, also influence the immune response by secreting pro- The ongoing “controlled inflammatory response”
even lethal, injury to the patient warrants highly spe- inflammatory mediators, including cytokines, chemo- associated with the epithelial cell damage, apoptosis,
cialized and effective cellular and noncellular defense kines, and adhesion molecules. They can also process and exfoliation is occurring constantly to maintain an
mechanisms against the “tube within the tube.” An invading microorganisms or absorbed toxins, neutralize effective biologic shield against its external environ-
increasingly recognized characteristic of individuals them, and then serve as antigen-presenting cells to T ment within the tube of the gut. Cell replacement must
who are susceptible to digestive diseases is the degree cells in the lamina propria’s immune system. Finally, it be common and robust to provide the billions of healthy
to which the epithelial lining provides an ineffective is important to mention the intricate systems within epithelial cells that coat the gut. When ongoing cellular
barrier and, thus, a “leaky gut.” This occurs in patients epithelial cells that are able to recognize when a cell is replacement is impaired, health is threatened. In the
with Crohn disease, celiac disease, food allergies, and being overcome by antigen excess, triggering intracel- esophagus, the nonkeratinized squamous cell epithe-
food intolerance. lular messengers to produce apoptosis. These dying lium is under the constant influence of shearing forces
cells are extruded constantly into the lumen and related to swallowed food and strong esophageal con-
The first line of defense from intraluminal contents replaced by new, healthy cells. Interposed between tractions as well as the caustic effects of gastroesopha-
is the partial barrier created by the glycocalyx coat epithelial cells are podocytes of subepithelial geal reflux. The increased rate of cellular replacement
secreted by submucosal glands, goblet cells, and epithe- dendritic cells, which are highly efficient antigen- in response to injury can be identified by the enlarge-
lial cells throughout the length of the gut. This thick presenting cells. ment of the rete pegs. Mucosal breaks, ulcerations, and
mucoid substance is a complex mixture of mucins, gly- bleeding result when this cellular replacement process
coproteins, and trefoil factor–like peptides. Its slippery Microorganisms can invade the gut by crossing epi- is overwhelmed. Inadequate replacement of the colum-
nature serves as a lubricant to reduce the shearing thelial cells (transcellular) or by passing between cells nar epithelium of the stomach and intestines occurs
forces produced by contractions and swallowed solids. in the process of translocation. Key to preventing such commonly in a more wholesale fashion in the setting of
In the stomach, mucus retards the diffusion of bicar- invasions are the cell-cell adhesion molecules, particu- hypotension and shock. In shock, the normally robust
bonate away from the epithelium to create a pH gradi- larly tight junctions (zonulae occludentes). Tight junc- supply of nutrients and oxygen provided to the gut by
ent that ranges from 1.0 at the surface of the mucus to tions are complex yet dynamic structures that selectively its rich vascular supply is diverted to the heart, kidneys,
a neutral 7.0 at the epithelial cell surface. In the intes- control the paracellular movement of antigens and and brain. Under such circumstances, if cells continue
tine, it serves to retard diffusion of foreign antigens and fluid to the underlying intraepithelial lymphocytes and to be damaged but are not replaced rapidly enough, the
microorganisms toward the surface while retaining lamina propria. When these gates to the paracellular gut’s integrity can be lost. When this occurs in the
secretory IgA molecules that have been released into space’s protective mechanisms are impaired, cells can stomach, diffuse hemorrhagic gastritis may result. In
the lumen, at the surface. This glycocalyx can also trap become damaged. In the upper gastrointestinal tract, the gut, mesenteric ischemia leads to increased leaki-
antigens within this sticky material to eventually be medications commonly damage tight junctions, permit- ness and translocation; if it is not corrected, it results
passed in stool. ting back diffusion of acid and submucosal injury that in the many potentially lethal complications of mesen-
can lead to ulcerations. In the intestine, translocational teric ischemia, including sepsis, bleeding, and, if not
The heterogeneous cells lining the gut all share the invasion is partially controlled by intraepithelial corrected, perforation.
ability to provide an effective physical barrier that is lymphocytes.
resistant to invasion of microorganisms and toxins and
to diffusion of electrolytes. Intestinal epithelial cells can

54 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 1-54  Overview of Upper Digestive Tract

Microbiome The variety and number of microorganisms MICROORGANISM CONCENTRATIONS (in CFU/mL)
that reside in the digestive tract is highly
Microbiota have long been known to be an unseen, diverse. The microbiota changes with Oral 109
ubiquitous majority teeming on every imaginable many factors including diet and Esophagus 106-7
surface upon and within the human body. These sur- medications and with hormonal
faces include the (1) conjunctiva, (2) skin, (3) respiratory changes, particularly in the vagina. Gastric 101-3
tract, (4) gastrointestinal tract, and (5) genitourethral Numbers express numbers of Prox SB 104
passages. The approximately 100 trillion bacteria in the microorganisms per mL as Ileum 106-8
human body form 2% to 3% of the average body mass CFU/mL (colony forming Colon 1011-12
and 55% of the dry feces mass, far outnumbering the units).
10 trillion human cells. Their aggregate metabolic
activity has earned them the collective name of the Probiotics
“forgotten organ.”
Capsules or yogurts containing Vagina 105-8
Contrary to popular belief, many bacteria can be live microbial food supplements
cultured, but the cumbersome techniques and long incu- (lactobacilli or bifidobacteria) PB PF
bation periods needed for culture have previously pro- AS
hibited the easy identification of bacteria and, in turn, Ileum
prevented scientific researchers from grasping their
clinical significance. The advent of deep 16S RNA Adherent substances bond Polysaccharide
sequencing has dramatically enhanced our ability to probiotic bacteria (PB)
simultaneously and accurately identify the presence of to intestinal epithelial Short-chain
individual species. Complementing this technology are cells (IE cell). fatty acids
the budding sciences of metabolomics and proteomics, Antimicrobial (SCFA)
which aim to interpret the clinical impact of the metabo- substances (AS) Butyric
lites and proteins generated by living organisms and antagonize carcinogenic Propionic
tissues. These technologies will reshape our understand- and pathogenic flora (PF) acetic
ing of how microbiota affect human health and disease.
IE cell Bacterial
Importantly, this commensal community does not enzymes
consist of bacteria alone but also contains countless
fungal and viral agents that cohabitate within an intricate Stimulated immunity and SCFA absorption
mucosal mosaic. Maintenance of this complex interplay
is thought to be critical to maintaining mucosal integrity They also extract short-chain fatty acids from dietary Probiotic bacteria produce enzymes that ferment
and overall health. On the one hand, innate immuno- fiber, specifically butyrate, which promotes colonocyte polysaccharides
logic and physiologic mechanisms maintain a healthy health. The nonspecific action of antibiotics disturbs is also a suggestion that intestinal microbiota may influ-
community that prevents pathogenic organisms from the healthy balance of microbes in the colon; this has ence psychiatric disease; this has given rise to the devel-
flourishing. On the other hand, multiple microbiota given rise to epidemics of severe Clostridium difficile opment of potential psychobiotics.
mechanisms promote mucosal integrity and host health. infection. Reintroducing healthy donor stool suspen- Countless studies have provided evidence that the
sions into an actively infected C. difficile patient reverses microbiota influence the immune system via direct and
Mucosal surfaces throughout the body demonstrate this dysbiosis to a healthy balance with a high rate of indirect mechanisms. Other disease states implicated
convoys of leukocytes regularly deployed for surveil- clinical cure. Also, periodontal science has demon- include rheumatologic disease, metabolic syndromes,
lance and phagocytosis of microbial offenders. Salivary strated that individuals with tooth and gingival disease obesity, and irritable bowel syndrome. The microbiota
enzymes contain lysozymes, IgA, and peroxidase, which are at double the risk for having coronary artery disease represent a new frontier for therapeutic exploration
begin the antimicrobial breakdown. The harsh acidity versus their counterparts with a healthy mouth. There that may allow us to moderate chronic illness via tradi-
of gastric secretions is bactericidal. Bile salts serve as tional medication and therapeutic multistrain collec-
detergents and, via micellar formation, envelop organ- tions of microbiota.
isms, inhibiting their direct mucosal binding. Pancre-
atic enzymes break down elements of bacterial cell
walls. And, of course, the migrating motor complex
regularly flushes out intestinal segments, preventing
stagnancy and bacterial overgrowth.

Indeed, a constant drama of urban microwarfare is
unfolding, in which healthy and pathogenic organisms
compete for domination and nutritional resources. For
instance, some species will compete for mucosal binding
sites to prevent more invasive pathogenic bacteria from
invading and causing illness. In fact, bacteria are known
to secrete lactate, peroxide, and even their own antimi-
crobial peptides known as bacteriocins, which serve to
keep adjacent competitors at bay.

Numerous clinical correlates exist to impress upon
medical science how critical these microorganisms are
to good health. Initially, a newborn possesses a sterile
gut. It is theorized that early luminal exposures between
the patient’s innate lymphoid system and consumed
nutritional elements, including ingested and inhaled
microbiota, will go on to shape the future development
of health and/or disease. For instance, newborns born
via cesarean section rather than natural vaginal delivery
are at increased risk for atopic illnesses such as asthma.
Infants who are formula fed rather than breast fed are
at increased risk for allergic disorders. Gut bacteria play
an important role in vitamin K and biotin synthesis.

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 55

Plate 1-55  Upper Digestive Tract: PART I

Adverse Effects of
Medications on the Upper
Digestive System

Many drugs adversely affect digestive system function INH, acetaminophen, Amphetamines
or mucosal integrity. Drug-induced liver injury is so hydralazine Decreased appetite
common that we have devoted an entire section of Part Inhaled steroids
III to this topic. Although a host of medications have Hepatitis Candida esophagitis
the unwanted potential for injuring the liver, the wise Immunosuppressants
clinician will consider all medications as potential Birth control pills, Candida esophagitis
causes of hepatic injury. Similarly, hydralazine, azathio- ceftriaxone, clofibrate Mucositis
prine, several agents that effectively treat HIV infec- CMV gastritis
tions, some antibiotics, and even steroids are known to Cholecystitis Calcium channel antagonists,
injure the pancreas. In a patient being evaluated for the emptying and cause gastroparesis. The effects of anti- caffeine, aminophylline
cause of acute pancreatitis, recently started medications cholinergic drugs on the motor and secretory activities Esophagitis
should be considered; importantly, a medication taken of the intestine are sometimes the primary therapeutic
for months may also cause pancreatitis. aim and sometimes an unwelcome by-product of Narcotics, anticholinergics,
therapy directed elsewhere. Hormones can also impair antidepressants
The most common mechanism of drug injury to the motility. Most notably, somatostatin analogs delay gall-
digestive system is alteration of the integrity of the bladder emptying and progesterone has an inhibitory Delayed gastric emptying
epithelial lining. Drugs may have a direct injurious effect on colonic contractions. (food in stomach)
effect or may medicate the impaired mucosal defense Imuran, GLP1 antagonist,
by indirect mechanisms. Thus, every assessment of a The parasympathomimetic drugs (e.g., methacholine, DPP4 inhibitors
patient presenting with a digestive organ problem must bethanechol), including those agents that inhibit the Pancreatitis
include a detailed history of both prescribed and over-
the-counter medications. This history should also NSAIDs, aspirin
include dietary supplements and herbal agents. Duodenal ulcer

The common and all-too-often life-threatening Magnesium, laxatives
adverse effects of nonsteroidal antiinflammatory drugs Diarrhea
(NSAIDs), including aspirin, are so important that
we have discussed them in considerable detail with Aluminum, iron, calcium,
Plate 4-51. NSAIDs are the agents that most commonly opioids, anticholinergics
cause mucosal injury, but a wide variety of other unre- calcium channel antagonists
lated drugs also cause direct mucosal injury. These
include iron supplements, potassium supplements, Constipation
bisphosphonates, tetracycline antibiotics, and quini-
dine. It has been shown that drinking 6 to 8 ounces of hydrolysis of acetylcholine by blocking the action of
fluid before and after swallowing these medications will cholinesterase (e.g., neostigmine), stimulate saliva pro-
reduce esophageal injury. The theory that food may act duction and gastric emptying.
as a buffer against the adverse effects of these drugs in
other organs is a reasonable but unproven one. Iron Drugs that either stimulate or inhibit the effects of
supplements not only can cause mucosal injury but also sympathetic nerves are far less active on the gastrointes-
may raise concern for bleeding when the stool turns tinal tract than on other systems. A potent vasoactive
dark gray, suggesting melena. In such cases, intravenous sympathomimetic used in a critical care setting,
supplementation, although more expensive, may also be however, often reduces gut blood flow, particularly to
more prudent. the stomach, which can lead to gastritis and delayed
gastric emptying.
Drugs that are antimetabolites often interfere with
mucosal integrity by reducing the normal defenses pro-
vided by the normally high frequency of cell turnover.
This is particularly true where cell turnover is most rapid,
as in the oral epithelium, distal esophagus, and stomach;
aphthous ulcers and even mucosal sloughing can be seen
in these areas. Methotrexate and chemotherapeutic
agents are most commonly associated with such injury.
Irradiation will cause a similar lesion, through the same
mechanism. In addition to this acute injury caused by
inhibition of cell turnover and repair, irradiation often
leads to mucosal atrophy, submucosal bleeding, endarter-
opathy, vascular ectasias, and mucosal bleeding.

Motility is commonly altered by medications. Medi-
cations with anticholinergic side effects can impair the
motility function of most, if not all, of the luminal
digestive organs, reduce esophageal clearance by reduc-
ing peristaltic amplitude, cause increased reflux by
reducing lower esophageal sphincter tone, delay gastric
emptying, and impair motility of the small and large
intestines. Caffeine primarily causes an adverse effect
by selective reduction of lower esophageal sphincter
tone. Opioids most commonly lead to gastrointestinal
symptoms by causing constipation due to the density of
opioid receptors in the colon, but can also delay gastric

56 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 1-56  Overview of Upper Digestive Tract

Smell Ventromedial hypothalamic area Thalamus
of food (inhibitory: “satiety center”)

Lateral hypothalamic area
(facilitative: “appetite center”)

Sight of food

Hunger and Appetite Touch I II Calcarine
(sucking Memory and/or fantasy fissure
Food intake is due to a complex interplay of emotional reflex) Geniculate bodies
factors, learned behaviors, CNS regulation, fat cell (schematic)
thermoregulatory effects, and the digestive system. It Taste of food Chorda V Dorsal nucleus
has become increasingly clear that the intake of food is tympani VII of vagus
influenced by what appears to be an adipose “set point,” VIII Nucleus of
which results in a relatively stable weight in most Hearing (sounds of solitary tract
individuals despite efforts to change their weight. food preparation, IX
The ingestion of food occurs in response to need call to dinner, X Dorsal root
(hunger) or desire (appetite). Hunger describes the bell, etc.) Decreased levels ganglion
complex behavioral responses evoked by depletion of of CCK, GLP-1, Vagus nerve T6
body nutrient stores required for metabolic needs. and leptin Ghrelin T7
Studies by Pavlov and his colleagues in the early 1900s T8
emphasized the importance of cortical functions and Adipose tissue Myenteric T9
the vagus nerve through learned behaviors and their KEY and T10
associations with food intake. The fact that food- Sympathetic efferents submucous
seeking behavior is manifested in the unconditioned Parasympathetic efferents plexuses
state, as in newborn or anencephalic infants or decer- Afferents (and CNS
ebrate animals, emphasizes the important role of lower Thoracic
brain functions, including the reticuloactivating system connections) splanchnic
and hypothalamus. Indefinite paths nerves
Enteric hormones
The digestive system has a major influence on appe-
tite and hunger. A common sensation described by Leptin
patients as hunger is discomfort localized to the epigas-
trium and perceived as emptiness, gnawing, or tension. Hunger contractions in stomach Celiac
The fact that such ‘hunger pangs’ are experienced by ganglion
individuals whose stomach has been removed or dener-
vated is evidence that hunger contractions are not simply angiogenesis, and other functions; it appears to primar- Fat stores, particularly of brown adipose tissue, also
related to gastric contractions. On the other hand, it is ily serve as the satiety hormone. Leptin modifies appetite influence appetite. Brown adipose tissue plays a major
clear that the stomach is the major source of the primarily through its release by white adipose tissue but role in thermogenesis and appears to be regulated by
hormone ghrelin, which is an important stimulant of is also synthesized and released by brown adipose tissue, the CNS hormone orexin. It may be more involved with
food intake. This 28–amino acid peptide is released skeletal muscles, the placenta, ovaries, mammary epi- energy expenditure than appetite per se. Orexin is a
from X/A-like cells in the oxyntic glands of the gastric thelial cells, and bone marrow. In the digestive tract, it neuropeptide hormone structurally related to the gut
fundus but is also found in the pancreas and small intes- is released by cells in the gastric fundus and by gastric hormone secretin. It is also released from the hypo-
tine. It is structurally related to motilin. Its release chief cells. It acts as an internal modulator of energy thalamus and is responsible for both arousal and
leads to increased gastric smooth muscle contractions homeostasis, metabolism, and cell replication. Although appetite. It increases lipogenesis. In addition to the
and stimulation of CNS appetite centers that stimulate its primary effects are thought to be mediated by its hypothalamus, it is also present in neurons throughout
food intake. effects on the hypothalamus, especially on serotonin the CNS. Orexin release is inhibited by leptin and
cells, there are leptin receptors throughout the body on increased by action of the gastric hormone ghrelin.
Anorexia is not a common symptom in patients with many types of cells. It is clear that leptin release is sup- Decreased orexin can lead to a feeling of lowered
complete denervation of the small intestine, as occurs pressed by fasting, well before fat stores per se are energy which may cause a person to eat more to acquire
in small bowel transplantation. On the other hand, hor- altered, and is increased by stress, insulin, and cortico- energy. Such reflexive food intake in the setting of
mones released as part of the phenomenon known as steroids and, paradoxically, in obese persons. reduced energy expenditure can contribute to obesity.
the ileal brake have a significant influence on appetite,
including peptide YY3-36, which suppresses food intake.
Surprisingly, basal levels and postprandial levels of
peptide YY are decreased in obese patients.

A variety of other gut neuropeptides influence food
intake. Neuropeptide Y, released from the pancreas as
well as the hypothalamus, increases food intake. Insulin
can also increase food intake. Cholecystokinin, released
primarily from the duodenum, reduces food intake.

In addition to influences from the CNS and digestive
system, adipose tissue also regulates appetite. The key
appetite suppressant leptin is synthesized and released
from adipose tissues. Leptin is a hormone with extra­
ordinarily broad influences on metabolism, growth,

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 57

Plate 1-57  Upper Digestive Tract: PART I

Disturbances of Hunger Hypermetabolic Diabetes Metabolic
and Appetite states mellitus syndrome

In addition to the broad sociologic and economic influ- Hyperorexia
ences on access to and intake of nutrients, food intake
is influenced by (1) volition, learned behaviors, and Pregnancy
psychiatric disorders; (2) gastrointestinal and systemic
hormones; (3) the microbiome; (4) CNS regulatory Parorexia Specific nutritional
mechanisms; (5) the presence of gastrointestinal or deficiency or need
systemic diseases; and (6) functional or mechanical (e.g., calcium, salt, etc.)
digestive tract disorders that retard the normal flow
of intraluminal contents. Some individuals have an Emotional: Pharmacologic: Excess Vitamin
amazing ability to lose weight by reducing calorie Anorexia Amphetamine, smoking deficiencies
intake, but diets in general have had a disappointingly nervosa digitalis
limited long-term impact on the management of
obesity. Brain-gut communications with ghrelin, leptin, Anorexia Gastrointestinal Dehydration
cholecystokinin, (CCK), GLP-1, neuropeptide Y, and disorders (e.g.,
orexin are potent mediators of appetite (see Plates 1-46 hepatitis, ulcerative
and 1-56). In the CNS, serotonin and neuropeptide Y colitis, etc.)
pathways are particularly active. Learned behavior and
visual, olfactory, and auditory stimuli initiate reflexes Febrile
via cortical connections to the hypothalamus and limbic states
system. These complex mediators interact in ways that
are incompletely understood to lead to a variety of Thyroid Adrenal Neurogenic Radiation
specific eating disorders. therapy

Polyphagia, overeating, binge eating, and obesity are Hypermetabolic states
among the most important issues influencing our
society. Hyperorexia, or food intake in excess of body Bulimia is a related condition in which the patient Impairment of appetite with excessive smoking may be
requirements even when it poses a severe risk to health, restricts nutritional intake by self-induced vomiting due in part to impairment of taste sensations. Impaired
is a formidable medical challenge. It is the most after a meal, often in a surreptitious manner, or by appetite is also common in patients with xerostomia
common preventable cause of a host of malignant, purging with laxatives. Rumination syndrome and cyclic following irradiation or with Sjögren syndrome.
endocrine, cardiovascular, musculoskeletal, and respira- vomiting are related disorders. Management should
tory disorders, as well as of cirrhosis and hepatocellular always include psychiatric consultation by experts in Street drugs, particularly cocaine, methamphet-
carcinoma associated with a fatty liver. In some persons, eating disorders. Hospitalization and enteral feeding amines, and other stimulants, are potent appetite sup-
such behaviors may be a reaction to stress, obsession, may be necessary in severe cases. Although the causes pressants and should be considered in the differential
or depression, but it is clear that learned, inherited, and are multifactorial and incompletely understood, genetic diagnosis of all patients with anorexia. Similarly, mari-
acquired factors influence overeating, as do genetic factors are often involved. juana and other forms of tetrahydrocannabinols com-
influences. The fecal microbiota, acquired during child- monly lead to cyclic vomiting that mimics bulimia.
hood and altered by antibiotics, influence the risk for Decreased appetite resulting from food aversion is
obesity. The hyperorexia of diabetes and hyperthyroid- known as sitophobia. This is common in patients with Parorexia is an abnormal desire for certain substances,
ism does not result in obesity, because nutrient stores painful swallowing (odynophagia) and other conditions such as the craving for salt in uncontrolled Addison
have been depleted by concomitant nutritional wastage that result in pain in response to food intake, such as disease or for chalk in calcium deficiency states. The
or energy expenditure. gastritis and gastric ulcers. Odynophagia results from desire in early pregnancy for sour foodstuffs or other
breaks in the oropharyngeal or esophageal mucosa. selective and often unusual foods is another example.
Anorexia describes any state in which the severe Its mechanism is incompletely understood.
depletion of body nutrients fails to lead to adaptive
behavior. The appetite is commonly impaired in sys-
temic disorders and disorders of the digestive tract,
including neoplasms, pancreatitis, hepatitis, and colitis.
The release of tumor necrosis factor alpha, interleukins,
and corticotropin-releasing hormone in these disorders
contributes to anorexia. Once poor intake has caused
calorie deficiency, ketone excess may lead to further
anorexia and food deprivation. The hormone orexin has
an important contribution to impaired appetite in sys-
temic diseases. Severe nutritional deficiency leading to
pancreatic and epithelial atrophy can further exacerbate
inadequate intake with malabsorption.

Several psychiatric disorders can lead to impaired,
even life-threatening, inadequate food intake, including
bulimia and anorexia nervosa. Anorexia nervosa is loss of
appetite amounting to a disgust or distaste for food and
a fear of gaining weight. The patient has intense con-
cerns about the body habitus and a phobia about being
overweight or gaining weight. Severe forms of anorexia
lead to nutritional and metabolic deficiencies, fluid and
electrolyte deficiencies, cachexia, osteoporosis, infertil-
ity, amenorrhea, heart damage due to a beriberi type of
condition, and death. Gastric emptying is often delayed
in such malnourished patients but should not be inter-
preted as the primary disorder.

58 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 1-58  Overview of Upper Digestive Tract

Oral andNasal (to be differentiated) Uremia Systemic
PharyngealHemangioma Hypertension (malignant)
Abuse/Munchausen Arteritis
Esophageal by proxy Sarcoidosis Hepatic Hematologic
Trauma Multiple myeloma
Overview of Pancreatic Duodenal Biliary Gastric
Gastrointestinal Bleeding Malignant tumors Respiratory (to be differentiated)
Jejunal and Ileal Benign tumors Colonic and Rectal
Bleeding is a common symptom of both benign and (including hemangioma) Polycythemia
malignant disorders of the digestive system. Bleeding, Caustic ingestion Purpura
even in the absence of other digestive tract symptoms Esophagitis Leukemia
such as pain, obstruction, or signs of perforation, always Varices Hemophilia
warrants a definitive evaluation because it may lead to Mallory-Weiss syndrome
a life-threatening loss of blood and is often associated (lacerations from vomiting) Liver cirrhosis (and other
with significant and/or potentially lethal disorders. The Peptic ulcer causes of portal
more evidence there is of bleeding (anemia, iron defi- Hiatal hernia hypertension)
ciency, or overt bleeding) the greater the likelihood that
a serious disorder is present. Advanced malignancies Bleeding into Varices
are common causes of bleeding, but most causes are abscess or tumor Diverticulum
benign and treatable with medication and/or endo- Cholelithiasis Ectopic pancreatic tissue
scopic techniques. Amyloidosis
Peptic ulcer Carcinoma
Evaluation of the cause of bleeding includes consid- Duodenitis Benign tumors
eration of the location of gastrointestinal bleeding; one Diverticulum (including polyps and
must also assess the severity and rapidity of blood loss. Hemangioma hemangioma)
Blood loss from the digestive tract is described as overt Ampullary tumor Peptic ulcer
when there is obvious bleeding and occult when bleed- Gastritis
ing can only be detected by stool testing, a drop in Pancreatitis Erosions
hemoglobin, or iron deficiency. Eroding carcinoma Foreign body

Overt bleeding from the upper digestive system pre- Peptic ulcer Polyps
senting as the vomiting of bright-red blood is hemateme- Meckel diverticulum Hemangioma
sis. Partially digested blood that has turned black (with ectopic gastric Amebiasis
appears in vomitus as black strands of mucoid material mucosa) Helminthiasis
or small specks of black described as coffee ground emesis. Helminthiasis Milk protein allergy in
Bright-red blood expelled from the rectum is hemato- Aneurysm eroding gut infants
chezia. Passage of black stool from overt bleeding is Mesenteric thrombosis Diverticulitis or
melena, which has a distinctive odor well known to gas- Intussusception diverticulosis
troenterologists and emergency physicians as an urgent Benign tumors (exophytic Ulcerative colitis (or
call for prompt intervention. Hematochezia may be or intraluminal, including other inflammatory
seen as droplets or staining of the toilet paper when it polyps and hemangioma) disease)
originates from rectal cancer or hemorrhoids, or it may Crohn disease Foreign body
fill the toilet bowel. In either situation, endoscopic Tuberculosis Carcinoma invading
diagnosis of the cause is necessary. Malignant tumors (from adjacent organs)
Necrotizing enterocolitis Hemorrhoids
Bleeding is often not recognized until a patient is in neonates Fissure
found to be anemic by physical examination or labora- Duplication cyst Rectal prolapse
tory tests. Iron deficiency in males of any age and all Solitary rectal ulcer
nonmenstruating females is commonly due to bleeding. is found, a diagnosis should always be sought. Distin-
Although iron deficiency in premenopausal women is guishing between occult bleeding and malabsorption is to describe such patients, including patients who have
more commonly due to menstruation, gastrointestinal difficult because bleeding from most lesions is intermit- had a high-quality evaluation with both endoscopy
bleeding should always be considered. Malabsorption is tent. For example, in patients with known colon cancer and a well-prepped colonoscopy by an expert. When
also a common cause of iron deficiency. This is particu- extensive enough to require surgical resection, only one obscure bleeding is finally diagnosed, it is usually found
larly common in patients with celiac disease and chronic in four stool tests for occult blood will be positive. The by endoscopy or colonoscopy, because lesions may be
gastric hypochlorhydria whether due to severe atrophic limited sensitivity of these tests necessitates repeating intermittent or even lead to bleeding in the absence of
gastritis or to chronic use of high-dose proton pump stool examinations in four to six specimens 2 or 3 days an obvious break in the mucosa, as occurs with Dieulafoy
inhibitors. Differentiating occult bleeding from malab- before one can be confident there is no active bleeding. lesions. If endoscopy and colonoscopy results are nega-
sorption is facilitated by point-of-service stool testing Repeat testing of stools, hemoglobin levels, and iron tive, techniques must be used that extend beyond the
for blood with paper tests that react to the presence of levels; keen judgment; and close follow-up are neces- reach of these standard procedures, including capsule
any oxidating substance (stool guaiac test) or immune sary when evaluating patients with suspected occult endoscopy, push enteroscopy, or single- or double-
reactions (fecal immune test for hemoglobin); the latter test bleeding. balloon enteroscopy. Radiographic tests that may be of
is much more specific but less sensitive for upper gas- value in the evaluation of such patients include nuclear
trointestinal sources and more expensive. When blood The most challenging patients are those who have medicine bleeding scans, angiography, and cross-
documented bleeding but for whom a definitive cause sectional imaging with computerized tomography (CT)
is elusive. The term occult gastrointestinal bleeding is used scanning.

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 59

Plate 1-59  Upper Digestive Tract: PART I

Diagnostic Aids in
Gastric Disorders

Every diagnostic evaluation must begin by taking a Barium swallow
skilled history and performing a physical examination,
but additional aids are usually necessary to make a PET scan: isolated,
definitive diagnosis that will provide a specific plan for resectable esophageal
effective treatment. Following the history and physical cancer
examination, laboratory testing and noncontrast chest
or abdominal radiographs are often obtained. Common Diagnostic Findings of Upper Gastrointestinal Disorders on Plain Chest or Abdominal Radiographs
radiographic findings on plain x-rays (no contrast agent
administered) for common upper digestive disorders Chest radiograph Esophageal perforation Mediastinal or cervical interstitial air, air-fluid level in
are shown. The value of more precise imaging tech- an abscess
nologies with endoscopic and radiographic studies is
discussed with Plates 1-61 to 1-64 and of breath testing Esophageal diverticulum Air-fluid level, often epiphrenic or in cervical region
with Plates 1-65 and 1-66. An important element of a (Zenker diverticulum)
thorough physical examination of a patient with symp-
toms of a digestive disorder is evaluation of the stool Esophageal cancer Widened mediastinum, elevation of the left hemi-
for blood. Detecting blood from the upper gastrointes- diaphragm, malignant pleural effusion
tinal tract using fecal occult blood testing with a guaiac-
based technology, while less specific, is more sensitive Achalasia Interstitial pneumonitis, mid-chest air-fluid level,
than fecal immune testing for hemoglobin because the widened mediastinum, absence of gastric air bubble
immunogenicity of a hemoglobin molecule released in
the esophagus or stomach can be degraded by pancre- Mycobacterial infection Calcified mediastinal lymph nodes, other evidence of
atic and small intestinal digestive enzymes. tuberculosis in the lung

Physiologic testing of acid production and exposure Foreign body Presence of density in posterior mediastinum or
and of motility functions of the upper digestive tract is epiphrenic area
a commonly used, invaluable tool. Three types of
esophageal and gastric pH monitoring are in common Abdominal Severe GERD Aspiration pneumonia, particularly of the right
use. The traditional esophageal pH study provided only radiograph Gastric perforation mid-lung, interstitial lung disease
a transnasal 24-hour study of reflux. It is time honored Outlet obstruction Free air under the diaphragm, particularly when not
and safe and provides accurate information about the accompanied by an acute abdomen
severity of exposure of acid in both the esophagus and Enlarged silhouette of air-fluid level in the stomach
stomach. Alternatively, an intraesophageal clip pH study
can be performed by placement of a pH electrode 5 cm Foreign bodies Coins, batteries, other swallowed foreign substances
above the gastroesophageal junction using endoscopy.
It has several advantages over the transnasal probe facility. The test involves little radiation, is easy to motility test. The capsule can be swallowed by a patient
because it is wireless and therefore does not have the perform, and has essentially no risk for the patient. The in the office, and recordings are made as the patient
inconvenience, embarrassment, potential risk, and dis- wide variability in normal emptying rates may affect the goes about normal activities.
comfort of the transnasal device. It records, for 48 results, however, as may a patient’s mood and overall
hours, the intraesophageal pH measures as the patient health, which may also cause emptying times to vary Gastric secretory physiology is most commonly eval-
eats and sleeps as usual; this can be a challenge with the widely (poor reproducibility). This has led to the rec- uated by a basal rate and then by a stimulated, titratable
transnasal device. The major disadvantage of both ommendation that recordings be made for a minimum gastric secretory rate. This test is very important in the
devices, however, is that pH recordings only report the of 4 hours and that a standardized meal be eaten. Alter- evaluation of acid secretion in patients who may have
severity of acid reflux. A major advance over both of natively, gastric motility functions can be evaluated, Zollinger-Ellison syndrome or other causes of hypergas-
these techniques is high-resolution manometry and the along with small bowel motility, by means of a capsule trinemia. Gastric acid secretory studies are described in
impedance reflux study. High-resolution manometry is greater detail with Plates 4-27 and 4-36.
performed with a probe that has multiple recording
electrodes, permitting a more rapid and accurate evalu-
ation of esophageal motility testing throughout the
length of the esophagus, without the annoyance of
moving the device. More importantly, the impedance
technology permits the evaluation of both acid and
nonacid reflux and fluid dwell time and a correlation
between manometry and bolus transit. This device is
limited by recording for only 24 hours and by place-
ment of the catheter transnasally, but the increased
accuracy and extensive diagnostic information provided
coupled with the very small diameter of the device make
it the procedure of choice for esophageal motility and
reflux studies.

Physiologic testing of gastric motility and pH physi-
ology are also commonly performed. Gastric motility is
most commonly evaluated after a patient has eaten a
meal of radio-labeled liquids and solids in the nuclear
medicine department of a hospital or an outpatient

60 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 1-60  Overview of Upper Digestive Tract
UPPER GI IMAGES

Overview of Imaging of the
Upper Gastrointestinal
Tract

Even after a careful history and physical examination, Endoscopic image of small clot within a small High stricture of esophagus demonstrated by
imaging of the gastrointestinal tract is often required to duodenal ulcer (”red spot”). barium swallow.
make the correct diagnosis. Risk factors involved and Cancer
the cost-benefit ratio should be taken into consider- Barrett adenocarcinoma seen endoscopically in Barrett
ation before proceeding with imaging in lieu of pro- distal esophagus.
longed careful observation or a therapeutic trial. The should also be the first step in the evaluation of a patient endoscopic studies. The professional fee for each is
presence or absence of “alarm signs and symptoms” can with suspected foreign body ingestion. In both situa- similar, but the associated technical fees are high for
aid this decision, including weight loss, nausea, vomit- tions, however, if these films are negative but suspicion both, vary greatly from ambulatory settings to hospital
ing, fever, age over 45, and evidence of bleeding, is high for a perforation or persistent foreign body, settings, and should rarely be used to determine which
including a positive test for occult bleeding, gross further cross-sectional imaging with a CT scan should study to choose. Contrast studies have no risk except in
bleeding, or anemia. Having particularly severe or be performed before barium or endoscopic studies are a patient with an underlying perforation (see below).
worsening pain should increase consideration of further performed. Contrast fluoroscopic tests must be performed in a radi-
testing, as should pain that does not respond to simple CONTRAST IMAGING OF THE UPPER ology department, so a patient must be able to be trans-
measures or that interrupts sleep. Imaging the upper GASTROINTESTINAL TRACT ported to that area. The patient must be able to swallow
digestive organs can be achieved by endoscopic or Because most disorders of the upper digestive system or have a nasogastric tube and should be able to cooper-
radiographic techniques. Endoscopic evaluation is often are epithelial in origin, the most common imaging ate with the radiologist’s efforts to position the patient.
the procedure of choice. studies ordered for evaluation of the esophagus or Contrast radiography is in some respects an art, and its
stomach are fluoroscopic x-ray contrast studies or accuracy depends considerably on the operator’s skill.
Radiographic testing includes noncontrast x-rays,
contrast fluoroscopic testing, and cross-sectional When ordering fluoroscopic radiographic imaging,
imaging. Cross-sectional imaging of the chest, esopha- one must determine which swallowed contrast material
gus, and upper digestive tract is performed most
commonly with CT scans. Other commonly used
cross-sectional imaging technologies include magnetic
resonance imaging (MRI) and positron-emission
tomography (PET). These techniques are best suited
for examining lesions in the wall of the digestive tract,
liver, or pancreas or when there is suspicion for lesions
extrinsic to the lumen. Arteriography is a commonly
used diagnostic and therapeutic radiographic study
valuable for evaluating tumor invasion and the site of
bleeding. Therapeutically, it is used to treat persistent
bleeding sources, to embolize, to deliver chemotherapy
to malignant lesions, or to repair surgical anastomotic
strictures.

Ultrasonography, with or without Doppler studies of
blood flow, is a very valuable means of evaluating the
liver, gallbladder, and pancreas and, in selected patients,
the intestines. It is rarely of value, however, in examin-
ing the esophagus, stomach, or duodenum. Ultrasonog-
raphy performed by a specially trained endoscopist is
the procedure of choice for diagnosing intramural
lesions and for staging tumors of the lung and gastro-
intestinal tract for possible mediastinal or celiac nodes.

Plain, noncontrast imaging of the abdomen and chest
can provide valuable diagnostic information in selected
esophageal and gastric disorders. A plain film of the
abdomen, often described as a flat plate or image of
the kidney, ureter, and bladder (KUB), can be useful in
the evaluation of intestinal gas or pancreatic calcifica-
tion. The addition of an upright film of the abdomen
and chest is often ordered as part of an obstruction
series. Delayed gastric emptying is suggested if the
gastric image is pronounced, but a definitive diagnosis
will require additional studies. Achalasia should be con-
sidered when the chest x-ray shows a widened medias-
tinum with an air-fluid level and no gastric air bubble.
If a perforation is suspected, an obstruction series is
urgently needed and is essential to look for mediastinal
air or free air under the diaphragm in the upright films.
An obstruction series, including neck and chest x-rays,

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 61

Plate 1-61  Upper Digestive Tract: PART I

Overview of Imaging of the
Upper Gastrointestinal
Tract (Continued)

is to be used. Barium should always be the contrast Plain radiograph (pseudoobstruction)
agent of choice when there is concern about the risk for
communication between the digestive tract and the
airway, either with aspiration or by fistula. Use of a
water-soluble contrast agent such as gastrografin in
such circumstances could lead to sudden pulmonary
edema and bronchospasm, with dire complications. In
contrast, water-soluble contrast such as gastrografin
should always be used first to evaluate the esophagus or
stomach for the presence of a perforation. Barium
leaking into the chest in esophageal perforation or the
abdomen in gastric perforation is very difficult to
remove and may later serve as a nidus for infection.
Techniques used add air to create a double-contrast
image and markedly increase the accuracy of the
examination.

Contrast imaging of swallowing disorders is particu-
larly valuable when transfer dysphagia is considered or
when a lesion in the neck or high in the esophagus is
suspected.

CROSS-SECTIONAL RADIOGRAPHIC IMAGING Barium swallow (achalasia)
OF THE UPPER DIGESTIVE TRACT
Computed tomography scan (Crohn disease)
CT scans are invaluable in the evaluation of unex-
plained pain, liver lesions, pancreatic lesions, and ity of filling times and differences in appearance with repeated x-ray exposures increase the risk for neo-
lesions that extend from or into a luminal organ. This and without contrast and in the venous phase. Iodinated plasms, particularly in younger patients. Such cancers
includes thyroid, lymphatic, vascular, or lung lesions contrast poses a substantial risk, however, of causing do not develop for many years, or even decades, so the
impinging on or invading the esophagus. Organs adja- renal dysfunction, particularly in patients with underly- magnitude of the risk is incompletely understood.
cent to the stomach and duodenum can impinge onto ing renal disease, diabetes, uncontrolled hypertension,
these upper gastrointestinal organs or be invaded by or dehydration. Patients are also commonly allergic to MRI does not carry a risk for renal injury or neo-
disorders originating from them, including the aorta, these dyes. A history of allergic reaction to shellfish or plasm. Gadolinium-based contrast used in MRI
kidney, pancreas, gallbladder, and liver. CT scanning is to previously administered dyes must be obtained enhances the value of the study by improving images of
also invaluable in the evaluation and staging of most because, although the reaction is most commonly mani- the vascular structures. This contrast can rarely cause a
cancers. fested by a rash, it can lead to anaphylaxis. Oral contrast serious skin injury known as nephrogenic systemic fibrosis,
material does not carry any of these risks but can only particularly in elderly patients or patients with impaired
MRIs are more accurate in characterizing vascular be used in patients who can swallow effectively or who renal function. During the MRI, the patient passes
lesions, including aneurysms, and tumors invading have a nasogastric tube. CT scanning is usually ordered through a ring; this may be problematic for patients
arteries and veins, including epithelial and stromal only rarely in a patient’s lifetime, but some patients who are claustrophobic or morbidly obese. Open MRIs
tumors, for staging of cancers and determining whether undergo multiple scans. There is concern that such can be ordered for such patients, but with a sacrifice in
they are surgically resectable. MRI can also provide accuracy.
highly accurate images of the biliary tree and pancreatic
duct (magnetic resonance cholangiopancreatography
[MRCP]).

PET scanning is a functional imaging technique
similar to CT scanning that uses various short-lived
radioactive tracers, most commonly fluorodeoxyglu-
cose. The radiation exposure is similar to that of CT
scans. PET scans are often able to identify metastatic
lesions that are missed or incompletely characterized by
CT or MRI studies.

All three cross-imaging techniques require transport-
ing the patient to the device and variable levels of
patient cooperation. This is not an issue for ambulatory
patients, but it becomes a major issue and risk to
patients who are severely ill, particularly those in an
intensive care unit. The patient must lie quietly and be
able to tolerate being moved into the confined space of
the circular device. CT scans and MRIs are often of
greatest value when viewed with intravenous contrast,
which also adds risk. Iodinated contrast agents are used
in CT scans to differentiate vascular structures. When
used in timed infusions, they can differentiate the rapid-

62 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 1-62  Overview of Upper Digestive Tract

UTILITY OF UPPER ENDOSCOPY

Endoscopic Evaluation of Endoscopic removal Snare with
the Upper Digestive Tract of gastric polyp fulgurating
current
Because of the increase in comfort, safety, and accuracy Band ligation of
of endoscopic examination, it has replaced barium esophageal varices
studies as the procedure of choice for evaluating the
esophagus, stomach, and small intestine and colon. Snare capture of
Upper endoscopy is very accurate and is considered the foreign object
“gold standard” diagnostic test for most luminal upper
digestive tract disorders. Barium contrast fluoroscopic Endoscopic image of spurting arterial blood UGI bleeding treated with
x-ray studies are highly operator dependent and limited from duodenal ulcer epinephrine injected by a needle
in quality in the best of hands. For example, barium
contrast studies will be able to diagnose fewer than 65%
of the causes of upper gastrointestinal bleeding (and
therefore are contraindicated in such situations).
Endoscopy can be performed in an ambulatory setting
and anywhere in the hospital, permits the taking of
pathologic specimens, and may be used to perform
therapeutic interventions. Nearly all patients prefer to
be sedated or even to be given monitored airway control
heavy sedation, but such comfort measures are not
essential for all patients and are not provided in all
countries. The ordering physician must know when to
use barium contrast studies performed by a radiologist
and when to use endoscopy.

It is important for the clinician ordering endoscopic
procedures to understand their special uses and quality
metrics and the advantages and disadvantages of barium
studies compared with endoscopic studies. Although it
is technically the more invasive diagnostic test, endos-
copy is perceived as being more comfortable because it
is performed with sedation, and, therefore, it is much
preferred by patients. Endoscopy is also preferred
because it is much more accurate and permits the taking
of specimens for cytologic, microbiologic, or patho-
logic assessment. It is also used to perform a wide
variety of therapeutic procedures. If appropriate, this
invaluable tool can be brought to the bedside of the
sickest patients in the hospital’s intensive care unit for
both diagnostic and therapeutic interventions. In con-
trast, all radiologic studies require the transportation of
the patient to the specialized x-ray equipment located
in the radiology department of the hospital, except
for the simplest of plain x-rays and ultrasound studies.
This section will briefly describe the process of upper
endoscopic procedures and the use of three upper gas-
trointestinal endoscopic procedures, endoscopy, endo-
scopic retrograde cholangiopancreatography (ERCP),
and endoscopic ultrasonography (EUS). The ordering
physician must appreciate when to use these studies
and the potential risks and quality metrics to look for
in the results.

PREPARATION AND SEDATION TECHNIQUES sible or prudent. Knowing the status of the patient’s protection of the airway by intubation. Thus the patient
Ensuring the patient’s safety is of the highest priority platelet count and coagulation tests is imperative if one must have taken no food by mouth for at least 6 hours
in endoscopy. One must ask if the procedure is clearly has any reason to suspect they are abnormal, especially and no clear liquids for at least 2 hours. Of course, these
indicated, whether this is the safest approach to getting if intervention is planned. If the patient has an active standard times for fasting should be longer in patients
the diagnosis or treatment, and whether this is the cardiac or pulmonary condition, including obstructive at high risk for aspiration, including those with achala-
optimal time in the course of the patient’s illness to sleep apnea, the patient must be assessed, if necessary sia and gastric emptying disorders. Special instructions
perform the procedure. Cardiac, pulmonary, and coag- by a cardiac or pulmonary specialist. Because morbidly should be given to patients regarding their blood pres-
ulation studies are not usually indicated, but they may obese patients are particularly at risk, office endoscopy sure and diabetic medications. In patients with active
be needed in select patients who have unusual risks. is not recommended for them, and they may require bleeding, the blood pressure and pulse should be made
The endoscopist must be aware of all underlying preprocedure assessment. as normal as possible by crystalloid fluid and, if neces-
medical conditions, all prescribed and over-the-counter sary, blood resuscitation. Before starting the procedure,
medications taken, and any concerns about the coagula- Once the procedure has been scheduled, the patient time should be taken to ensure that all providers and
tion status. If possible, anticoagulants should be held if must be aware of her or his responsibilities. One of nurses are aware of the patient’s risk factors, including
intervention is anticipated, but this is not always pos- the most common severe complications from upper allergies, risks of the procedure to be performed, and
endoscopic procedures is aspiration pneumonia. Except risks of any intended interventions.
in select cases, the procedure is performed without

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 63

Plate 1-63  Upper Digestive Tract: PART I

Sphincterotomy for release of stone in ampulla of Vater
Duodenal wall
Common bile duct

Endoscopic Evaluation of Pancreatic duct
the Upper Digestive Tract Stone

(Continued) Sphincter ampullae

ENDOSCOPY AND ENTEROSCOPY Multiple large lesions found by endoscopy in stomach during Endoscopic appearance did not clearly
Endoscopy is generally a very safe test and can be per- evaluation for iron deficiency. indicate whether larger lesions could be
formed in nearly all patients with ease and no antici- safely removed endoscopically.
pated ill effects within 5 to 15 minutes (or longer if
interventions are performed). It can provide highly Liver
accurate imaging of the entire upper digestive system
to the distal duodenum or, if enteroscopy is performed, mp
well into the jejunum or ileum. Histologic, micro-
scopic, or cytologic specimens increase the diagnostic sm
accuracy with negligible risk. Interventions are com- m
monly performed with endoscopy, including dilations
of the esophagus or duodenum, the placement of stents
to treat resistant strictures or cancers of the esophagus
or duodenum, and the placement of feeding tubes. The
key to quality is adequate analysis of all parts of these
organs with photo documentation and the taking of a
sufficient number of biopsies in accord with published
guidelines. It has been shown that the errors of upper
endoscopy occur when sufficient time is not taken to
examine parts of structures that are challenging to see
clearly or to achieve a thorough evaluation. This
includes examining all of the esophagus; documenting
the site of the squamocolumnar junction; examining in
detail the fundus in a retroflex view; examining the
angularis, pylorus, and all parts of the bulb of the duo-
denum; and reaching at least the third part of the duo-
denum. The guidelines for diagnosing specific upper
gastrointestinal disorders should be understood by the
ordering physician (see Sections 2 to 4). For example,
one should obtain at least six biopsy specimens through-
out the esophagus to rule out eosinophilic esophagitis,
nine specimens of gastric ulcers to rule out malignancy,
and six specimens of the duodenum, including two in
the bulb region, to rule out celiac disease.

ENDOSCOPIC RETROGRADE GB Endoscopic ultrasound image
CHOLANGIOPANCREATOGRAPHY clearly showed lesions to be
Mucosal sm limited to mucosa.
ERCP will be discussed at length in the chapter on polyp mp All were safely removed and
biliary disorders. Only very highly skilled endoscopists found to be benign but
perform this procedure, usually after a fourth year of presumably premalignant
training or many years of experience. It can often adenomas.
provide therapeutic intervention that avoids major
surgery, including bile duct stone extraction and ductal endoscope that has been modified by the placement of It also permits the collection of cytologic specimens by
stenting. Diagnostic ERCP has rarely been indicated one of several transducer types at the tip of the scope. using fine-needle aspirates of the lesions and/or biop-
since EUS and MRCP have become available, both of It has become the procedure of choice to examine nodes sies. In the setting of cysts or abscesses, EUS can be
which can examine the bile duct and ampulla in detail adjacent to abdominal organs and the esophagus; the used diagnostically to collect intralesional fluid for
with negligible risk. In years past, it was common to distal common bile duct; submucosal lesions and pan- culture, cytologic, or biochemical assessment or thera-
hear that the duct could not be cannulated, but in expert creatic lesions; and fluid collections. It is highly accurate peutically to drain the lesion. It can also be used to guide
hands, this is now a rare occurrence. Because of its for lesions that may be only millimeters in diameter an interventional procedure such as pancreatic cyst
potential duration, this is the one upper endoscopic because the transducer is placed directly on the lesion. drainage by creating an endoscopic cyst gastrostomy.
examination that may require preemptive planning for
intubation and general anesthesia.

Endoscopic Ultrasonography
EUS is performed by endoscopists who are trained at
length on its uses. The procedure is performed with an

64 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 1-64  Endoscopy Overview of Upper Digestive Tract
Biopsy Endoscopy affords
Histologic and Cytologic forceps direct observation
Diagnosis and tissue sampling
ability

Safe, minimally invasive techniques have been devel- Cytology Duodenal ulcer
oped to definitively diagnose most digestive disorders, brush
including the acquisition of cytologic or histologic Gastritis with erosions
specimens. This has been particularly important in Radiography (barium examination)
malignant disease, where it is rarely, if ever, acceptable Deformed duodenal bulb
to consider treatment without first making a “tissue Barium-filling ulcer crater risk of finding an alternative diagnosis, particularly a
diagnosis.” In many more cases, cytology or pathology ogy, include the risk of discomfort or bleeding; even life-threatening disease, to determine whether the
obtained by endoscopy can exclude a malignancy or multiple passages of the needle may not provide ade- taking of endoscopic photographs or histologic or cyto-
diagnose a malignancy that does not require surgical quate cellular data. The risk of inadequate cellular data logic specimens is warranted. To aid in this decision,
intervention (e.g., gastric mucosa-associated lymphoid can be reduced by having a cytology expert in the pro- various alarm signs and symptoms have been identified
tissue [MALT] lymphomas, which are treated with anti- cedure room to assess the quality of such specimens. for most symptom complexes. These include symptoms
biotics; malignancies that are diffusely metastatic and that persist after effective therapy or that interrupt
therefore beyond the benefit of surgery). The problem of being able to provide definitive his- sleep; age over 45 years; the presence of fever, weight
tologic or cytologic information for guiding treatment loss, nausea and vomiting, or anemia; or gross blood
In many situations, highly accurate photo documen- occurs all too commonly with the myriad of functional loss. Experts have also identified a number of criteria
tation may be a most valuable tool in making the diag- gastrointestinal disorders for which no histologic or by which a diagnosis of a functional disorder can
nosis and guiding therapy. Much more often, however, cytologic specimen can provide a definitive diagnosis. be made without ordering unnecessary testing, most
biopsies are essential, even at times when the gross These disorders are particularly challenging because notably the ROME criteria. Although they are not
appearance is normal. Common examples of this in the they are common, lead to substantial degradation in the without controversy, such approaches provide a means
upper gastrointestinal tract include eosinophilic esoph- quality of life, and lead to a loss of productivity and by which excessive endoscopic and radiologic testing
agitis and celiac disease. Histology can also determine success at school or work, but they almost never lead to can be minimized.
the cause of what may appear to be mild nonspecific serious complications or shortening of the life span.
erythema to reveal that it is due to an infection or The astute clinician must use judgment based on the
Crohn disease. Histologic specimens obtained by endo-
scopic biopsies or cytologic specimens provided by
brushes or fine-needle aspiration provide the clinician
with definitive data with which an effective therapeutic
strategy can be designed.

When receiving the results of a procedure, the order-
ing clinician should clarify whether biopsies or cyto-
logic specimens were taken and the number of
specimens taken. Providing the pathologist with a suf-
ficient number of specimens to make a definitive diag-
nosis is a key quality metric. It is rarely, if ever,
appropriate to take fewer than three specimens; taking
this number does not increase the number of passes of
the forceps (time) needed or the expense of the proce-
dure. Endoscopists should also be adept at directing the
biopsy forceps. Receiving an endoscopic report with
photo documentation of an abnormality but with a
pathology report that is read as normal should raise
concern. The specimen should be taken with an optimal
orientation. Taking biopsies tangentially to the orienta-
tion of the mucosa makes it difficult to provide a defini-
tive and accurate diagnosis. Orientation is particularly
important in the duodenum, where the biopsy should
be obtained across a fold (plicae circulares) and perpen-
dicular to the mucosa to accurately assess villous height
and crypt depth, as is critical in assessing the diagnosis
and severity of small intestinal mucosal diseases such as
celiac disease.

Most exfoliated cytologic specimens are obtained by
endoscopically guided brush cytologic procedures or
interventional radiology experts. Abrasive brush devices
for obtaining tissue for cytologic diagnoses, including
an intraesophageal brush, have been proposed as a less
invasive means of diagnosing esophageal disorders.
Although the risk is lesser than with endoscopy, the
procedure rarely provides definitive data for treatment
and management. Potential limitations of guided fine-
needle aspirations, whether obtained by EUS or radiol-

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 65

Plate 1-65  Upper Digestive Tract: PART I

BREATH TESTING
Bacterial Overgrowth Breath Test

Lactulose ingested

Breath Values (PPM) 150
140
130
120 Second peak in the colon
110
100

90 First peak in the small bowel
80
70
60
50
40
30
20
10

0
1 2 3 4 5 6 7 8 9 10 11 12

SIBO Sampling Times (Min)
Normal

Breath and Stool Testing

Testing exhaled breath or discharged stool can provide of this infection is clinically important. This includes ized patients often complain of diarrhea when the
invaluable information in the diagnostic evaluation of patients who have had complications from H. pylori problem is actually fecal incontinence. This may result
disorders of the digestive system. Breath and stool infection, such as complex peptic ulcers and MALT from inadequate intake of fiber in the diet to produce
testing can be performed at the point of service or can lymphomas. formed stools, loose stools from medications, and
require more sophisticated biochemical or radiophar- deconditioning or illness that leads to weakness of all
maceutical analysis. Appreciating the spectrum and STOOL TESTING muscles, including those contributing to continence.
value of such tests enhances one’s diagnostic acumen. It is important for clinicians to be familiar with the most Increased liquid or fecal incontinence may also be due
common stool tests, their strengths, and their limita- to paradoxic diarrhea, in which there is frequent passage
BREATH TESTING tions. As in all diagnostic evaluations, an evaluation of of small volumes. Patients with subacute or chronic
The number and uses of breath tests continue to be abnormal stool output should begin with a description diarrhea often suffer from altered bowel habits related
expanded. In ancient times astute diagnosticians of the stool being evacuated. It must be admitted that to irritable bowel syndrome but do not expel more than
reported the ability to detect disorders of digestion and observing the consistency, color, and other factors of 250 mL of stool necessary to make an objective diag-
the liver from the patient’s breath. A feculent odor of the appearance of the stool contributes only infre- nosis of true diarrhea. Quantifying stool output while
breath can be associated with achalasia, gastroparesis, quently to the diagnostic information obtained by a the patient is fasting is also a very useful way of distin-
small intestinal bacterial overgrowth, and partial small carefully extracted history and the application of appro- guishing diarrhea due to malabsorption (osmotic diar-
bowel obstruction. Fetor hepaticus is sometimes noted in priate tests. Having stated that, it must be emphasized rhea) from diarrhea due to an inflammatory disorder, a
patients with cirrhosis. that the accurate description of stool color continues to secretagog, or surreptitious diarrhea.
have high diagnostic value. An acholic stool will certainly
An excess of hydrogen concentration in the breath suggest biliary obstruction. A tarry stool indicates gas- The most common test of the stool is to determine
soon after ingestion of nutrients is used by gastroenter- trointestinal bleeding, usually from the upper levels, the presence or absence of mucosal breaks leading to
ologists with greater precision than can be expected and a stool colored red with blood means bleeding in the bleeding. Fecal occult blood tests and the fecal immune
by olfaction alone to identify even mild disorders of lower intestinal tract. test for human hemoglobin have been reviewed in the
small intestinal bacterial overgrowth. The same tech- section on gastrointestinal bleeding.
nology can be used to diagnose common disaccharide Although many descriptors have been considered
malabsorption problems with sucrose or lactose when excessive, attention to the appearance of the stool is Patients suspected of having intestinal infections
these sugars are used as a substrate. Collection of rarely useful. Furthermore, patients often complain of often undergo stool testing; most patients who develop
radiopharmaceutical-labeled substrates can also be used increased stool odor, but all stool is malodorous. One new onset of diarrhea have an infection. The stool test
to diagnose these and other malabsorption disorders. widely used scale of stool appearance that has been for infection often begins by looking for fecal leuko-
validated is the Bristol Stool Scale. Using this scale can cytes (stool white blood cells). This test is positive when
Breath tests are widely used to diagnose the effective- increase the objective assessment of the severity of dis- enteroinvasive, severe enterotoxic, and autoimmune
ness of antibiotic therapy for Helicobacter pylori. These ordered defecation and enhance the patient’s ability to enteritis or colitis is the cause. False-negative tests for
tests capitalize on the fact that these fascinating organ- communicate concerns. fecal leukocytes may occur when stool volumes are very
isms can influence the pH of their environment within high or when the stool specimen is not collected as a
the gastric mucus layer by splitting ammonium ions. The stool volume output over 24 hours should be fresh specimen, is not placed in preservative, or is con-
Tests of exhaled breath after the ingestion of C13-urea determined in any patient with diarrhea that develops taminated by urine.
is standard for select patients for whom the presence in the hospital or who complains of chronic diarrhea.
In both settings, stool output is often normal. Hospital- Specific causes for acute diarrhea can be determined
by several mechanisms. Enteroinvasive bacterial infec-
tions are detected by culturing the stool. When Yersinia

66 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 1-66  Overview of Upper Digestive Tract
STOOL TESTING

Clay-colored Tarry stool Blood-stained
stool (acholic) (melena) stool (local

lesions of left
colon and anus)

Breath and Stool Testing Ulcerative Ribbon stool Steatorrhea
colitis stool (irritable bowel (malabsorption)
(Continued) (loose, bloody, with syndrome)
much mucus and pus)
colitis is suspected, special culture techniques should be
requested using selective media such as MacConkey Normal stool: partially digested muscle Normal stool: spiral vegetable fiber Ulcerative colitis: numerous pus cells,
agar. DNA testing of specific virulence markers is also fiber (lower left), several vegetable cells below, particle of leafy vegetable singly and in clumps, fragmented
valuable for bacteria such as Yersinia and Escherichia coli, (center), vegetable fiber (upper right) above, no inflammatory elements remnant of vegetable material
which are plentiful in the microbiota in nonpathogenic amid amorphous debris, mostly bacteria present (right center)
strains. Identifying the specific bacterial cause of diar- and unrecognizable remnants of digestion
rhea is important to direct antibiotic treatment and
identify a specific carrier of transmission in epidemic specimens will detect excess osmolality not explained fermentation or steatorrhea caused by the complexity
infections. Helminthic infections and parasitic causes of by electrolytes alone (hyperosmolar). The specimen of mechanisms needed to absorb fatty nutrients into
acute diarrhea can be detected by expert microbiology should also be tested for phenothalines and magnesium, cells that primarily consist of water. Steatorrhea can be
technicians. False-negative tests are common, however, indicating surreptitious laxative use, and for stool cre- detected by using a qualitative Sudan stain slide or
and fresh specimens should be evaluated three times to atinine to rule out contamination by urine. Performing quantitatively by accumulating a 24-hour collection of
be certain that a test for ova and parasites is negative. the test is not only unpleasant for the patient and nurse, all fecal output while the patient is on a 100-g fat diet.
A specific cause for infectious diarrhea often goes it is technically challenging, because if it is not iced This is a difficult diet to follow and a very challenging
unidentified because most infections are due to viruses, continuously, it will become uninterruptable because of collection to make.
toxins, or a strain of E. coli.

The presence of specific infectious agents can be
detected by testing the stool for DNA to common
pathogens or the toxins they release. This is most com-
monly performed to detect C. difficile superinfection in
patients whose normal microbiota has been altered by
antibiotics. Cultures can be used, but sensitive assays
for toxin are the most rapid means of detecting this
potentially lethal infection and in detecting if the most
lethal form of the disease (NAP-1) is present.

Inflammation in the intestinal tract can be detected
by identifying leukocytes or their by-products in the
stool including lactoferrin, myeloperoxidase, or cal­
protectin. Blood tests such as sedimentation rate or
C-reactive protein can also reveal gut inflammation,
but erroneously normal results are not infrequently
encountered.

Evaluation of chronic diarrhea should lead to a
consideration of malabsorption. This should begin by
collecting several stool specimens in ice and sending
them to the laboratory to be evaluated for sodium
and potassium and stool osmolality. When malabsorp-
tion is present, a correctly performed comparison of

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 67

SECTION 2 

MOUTH AND PHARYNX

Plate 2-1  Upper Digestive Tract: PART I

Development of the thyroid and parathyroid glands

Development of Mouth 4th aortic arch 1st pharyngeal
and Pharynx pouch
4th branchial
The lining of the primitive gut tube is derived from the cleft 1st branchial cleft
embryonic endoderm and the supporting tissues and 4th pharyngeal Internal
mesentery from the visceral layer of lateral plate meso- pouch carotid
derm. The amniotic cavity expands around the develop- Dorsal aorta artery
ing embryo to create the body wall but leaves the 4th branchial 1st aortic
endoderm/ectoderm connection at the oropharyngeal arch arch
membrane and caudally at the cloacal membrane. The Trachea Disintegrating
early mouth, stomodeum, is formed by the ectoderm and Esophagus buccopharyngeal
the early pharynx by the endoderm. The developing Lung bud membrane
pharynx is properly part of the foregut and it extends Maxillary
from the oropharyngeal membrane to the respiratory process
diverticulum. During the fourth week of development,
the oropharyngeal membrane ruptures. Thyroid gland

A large fold of mesenchyme located over the eventual 1st branchial arch
forehead, the frontonasal prominence, extends inferiorly (mandibular)
to form the superior border of the stomodeum. Two Heart
maxillary prominences are found on each side of it, and
a single, fused mandibular prominence borders the sto- Pharynx (ventral view) 4th week Pharynx and derivatives (between 6th and 7th weeks)
modeum inferiorly. The frontonasal prominence devel-
ops two nasal placodes that hollow out to become the Mouth cavity Pharyngeal Foramen
nasal cavities. On either side of the placodes are the Thyroid gland cavity cecum
lateral and medial nasal prominences. The lateral promi-
nences fuse with the maxillary prominences to create I Pharyngeal pouches Tongue
the nasolacrimal grooves. The medial nasal promi- 1st pouch Epithelium
nences fuse with each other on the midline to form the of larynx
philtrum of the upper lip and also with the maxillary II 2nd pouch Trachea Lateral
prominences to create the upper lip. The medial nasal 3rd pouch thyroid
prominence also carries the mesenchyme that will III Parathyroid III lobe
differentiate into the primary palate, which fuses with Thymus Thyroid
the palatine processes of each maxilla to form the IV isthmus
hard palate. Trachea 4th pouch
Lung bud
The pharyngeal (branchial or gill) arches are found Parathyroid IV
on both sides of the developing neck. These arches Esophagus
consist of mesenchyme from neural crest cells, which
form the connective tissue structures of the face and Esophagus
direct the formation of the other structures thereafter.
Each arch contains a cartilage core, an aortic arch, a The cartilage of the third pharyngeal arch creates the nants of the first pouch, with the tympanic membrane
skeletal muscle, and a cranial nerve. remainder of the hyoid bone. The only muscle derived separating them.
from it is the stylopharyngeus, which is innervated by
The first pharyngeal arch, which is supported by the the glossopharyngeal nerve. The second, third, and fourth pharyngeal grooves
Meckel cartilage, gives rise to the maxillary and man- fuse and migrate into the developing neck as they are
dibular prominences, mandible, incus, malleus, and The fourth pharyngeal arch gives rise to (most of) the overgrown by mesenchyme, briefly forming a cervical
other facial bones. The muscular mesenchyme therein thyroid cartilage. The vagus nerve innervates the cyst that dwindles and disappears. The second pharyn-
is innervated by the trigeminal nerve, and it differenti- muscle mesenchyme of the fourth arch, which will give geal pouch forms the bed of the palatine tonsil as lym-
ates into all the muscles innervated by that nerve. rise to all the pharyngeal and palatine muscles apart phocytes migrate into its hollow, medial side. A dorsal
from the stylopharyngeus (IX) and the tensor veli pala- extension of the third pouch forms the inferior parathy-
The second pharyngeal arch is supported by the Reichert tini (V3). The external branch of the superior laryngeal roid gland, and a ventral extension forms the thymus.
cartilage, and it gives rise to the lesser horn and part of nerve (vagus) innervates the cricothyroid and cricopha- Similarly, a dorsal extension of the fourth pouch forms
the body of the hyoid bone, styloid process, and stapes. ryngeus muscles. the superior parathyroid gland and a ventral extension
The muscular mesenchyme in the second arch is inner- to the calcitonin-producing C cells of the thyroid gland.
vated by the facial nerve, and it differentiates into all The fifth pharyngeal arch exists in some animals but
the muscles which that nerve innervates. The second not in humans. However, the sixth pharyngeal arch and The tongue forms in the anterior part of the develop-
arch, in conjunction with the first, will also form the its cartilages give rise to the rest of the thyroid and all ing mouth as two lateral lingual swellings and one medial
auricle of the ear. the other laryngeal cartilages. The muscle mesenchyme lingual swelling, which enlarge and fuse. The muscles
in this arch is innervated by the recurrent laryngeal developing deep to these swellings are derived from
nerve, a branch of the vagus, which innervates the somites innervated by the hypoglossal nerve. The
intrinsic laryngeal muscles. lingual swellings are located in the floor of the first
arch, and their surface lining is innervated by the man-
The spaces between arches on the exterior of the dibular branch of the trigeminal nerve. The rest of the
neck form pharyngeal grooves, and those spaces on tongue forms deep to the second, third, and fourth
the interior side form pharyngeal pouches. The first pha- arches. A small diverticulum forms in the floor of the
ryngeal groove is located between the first and second mouth between the second and third arches. This is the
pharyngeal arches; it deepens toward the first pharyn- foramen cecum, and it will extend inferiorly and eventu-
geal pouch until only a thin membrane separates them. ally separate from the tongue, travel along a pathway
The external auditory meatus is the derivative of the first called the thyroglossal duct, and become the thyroid gland.
groove, and the middle ear and auditory tube are rem-

70 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 2-2  Mouth and Pharynx

Philtrum
Soft palate
Palatopharyngeal arch
Uvula
Palatoglossal arch
Palatine tonsil
Posterior wall of pharynx

Frenulum of
upper lip

Oral Cavity

The mouth, or oral cavity, is the beginning of the ali- Lingual minor salivary gland
mentary canal. Its roof is formed by the palate, the Deep lingual artery and veins and lingual nerve
tongue rises up out of its floor, and the cheeks and lips
form its boundaries laterally and anteriorly. The mouth Fimbriated fold
communicates anteriorly with the external environment Submandibular duct
by the rima oris, or oral orifice, and posteriorly with the
pharynx through the isthmus of the fauces. The oral Sublingual gland
cavity is divided into the vestibule and oral cavity proper Frenulum of tongue
by the teeth and alveolar processes of the mandible and Sublingual fold with openings of sublingual ducts
maxilla. When the mouth is closed, these two parts are
connected only by the small spaces between the teeth Sublingual
and a variable gap between the last molar tooth and the caruncle with
ramus of the mandible, through which a catheter can opening of
be passed for feeding when the jaws are closed tightly submandibular
by muscle spasm. duct (of Wharton)

When the lips are everted, a midline fold of mucous Frenulum of
membrane, known as the frenulum, can be seen extend- lower lip
ing from each lip to the adjacent gum. These frenula
may cause problems when fitting artificial dentures. Tubercle of upper lip
Also in the vestibule, opposite the crown of the second Parotid papilla with
maxillary molar tooth, is a small eminence through opening of parotid
which the duct of the parotid gland opens. These struc- duct (of Stensen)
tures of the vestibule are readily visible and can usually
be felt by the tongue. Many small glands are located in midline is the frenulum of the tongue. Immediately lateral By direct examination of the open mouth, in addition
the mucous membrane of the lips (labial glands) and of to each side of the frenulum is a sublingual caruncle, at to the structures described above, one can see the
the cheeks (buccal glands), which empty their secretions the apex of which is the opening of the submandibular palate, the palatoglossal fold, and the palatopharyngeal
directly into the vestibule. duct. Running posterolaterally from the sublingual car- fold, with the palatine tonsil between them, the teeth,
uncle is a raised fold of mucosa caused by the underly- and the tongue.
The lips (upper and lower) are extremely mobile ing sublingual gland, with openings of several small ducts
folds, which form the margins of the rima oris and meet of this gland scattered along it. At each side of the In an at-rest state, the upper and lower teeth are apt
laterally at the right and left angles of the mouth, where undersurface of the tongue is the fimbriated fold and, to be slightly separated from each other, the tongue is
they become continuous with the cheeks. The frame- medial to that, the deep lingual vessels are visible through at least partially in contact with the palate, and the
work of the lip is formed by the orbicularis oris muscle, the mucous membrane. vestibule is nearly obliterated by the lips and cheeks
external to which is skin with its subcutaneous tissue lying against the teeth and gums.
and internal to which is the mucous membrane. The
red area of the lip has an intermediate appearance
between the cheek skin and the mucous membrane.

The general structure of the cheek is similar to that
of the lip. The framework is formed by the buccinator
muscle, strengthened by a firm fascial layer, with skin
and subcutaneous tissue external to it and a mucous
membrane on the internal side. On the external surface
of the buccinator muscle, at the anterior border of the
masseter muscle, lies the buccal fat pad, which is espe-
cially prominent in the infant.

When the tip of the tongue is turned superiorly and
posteriorly, several structures come into view. In the

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 71

Plate 2-3  Upper Digestive Tract: PART I

Mandible Condylar process Head
Pterygoid fovea
The mandible, or jawbone, forms the bony framework Coronoid process Neck
for the lower part of the oral cavity and the skeleton of Mylohyoid groove
the lower part of the face. It has a U-shaped body, with Mandibular notch
a broad flat ramus running superiorly from each end of Retromolar fossa Lingula
the body. Oblique line Mandibular
Submandibular fossa foramen
The area of fusion of the right and left halves of the
body of the mandible at the anterior midline is the Mylohyoid line Ramus
mandibular symphysis. At the inferior anterior surface Sublingual fossa
of the symphysis is a triangular elevation called the Interalveolar
mental protuberance, the lower outer angles of which are septa
the mental tubercles. At the inferior part of the inner
surface of the symphysis is a variable elevation, the Alveolar part (crest) Angle
mental spine or spines, which may be present as a single Mental foramen
eminence or as two eminences, one superior and the Mental protuberance Body
other inferior. These give origin to the geniohyoid and Mental tubercle
genioglossus muscles. Base of mandible Condylar process
Lingula
Each half of the body of the mandible has an upper Coronoid process Mandibular foramen
and a lower part, the arch of the lower part being wider Head Mylohyoid groove
than that of the upper part. The upper part is the alveo- Neck
lar process, so called because it contains the sockets for Ramus
the lower arcade of teeth. The lower part, or body of the Mandibular notch
mandible, has a much greater proportion of compact Pterygoid fovea
bone. Just lateral to the symphysis on the lower border
is an oval depression or roughened area for the attach- Mylohyoid line
ment of the anterior belly of the digastric muscle, the
digastric fossa. On the external surface of the mandibular Angle
body, inferior to the second premolar tooth, is the
mental foramen, by which the mental branches of the Body
inferior alveolar nerve and vessels leave the mandibular
canal. Also on the external surface is an ill-defined Submandibular fossa
oblique line that runs from the mental tubercle to the
anterior border of the ramus. Sometimes it may start Sublingual fossa
from the lower border of the mandible inferior to the
molar teeth, or there may be lines from each of these Digastric fossa
places that meet as they run posterosuperiorly. On the
internal surface of the mandibular body, a ridge of bone Superior and inferior mental spines
runs obliquely from the digastric fossa to the level of (genial tubercles)
the socket of the last molar tooth. This ridge gives
attachment to the mylohyoid muscle and is therefore Mandible of aged
known as the mylohyoid line. Superior to the mylohyoid person (edentulous)
line is a shallow sublingual fossa, in which lies the sub-
lingual gland, and inferior to the mylohyoid line is the groove runs anteroinferiorly from it for a short distance. makes up most of the body. After full development it is
fossa for the submandibular gland. Projecting superiorly from the superior border of the about halfway between the upper and the lower borders.
ramus are the triangular coronoid process anteriorly and When an individual becomes edentulous, much of the
The ramus presents a medial and a lateral surface as the condylar process posteriorly, with the mandibular notch alveolar process is resorbed, and the mental foramen
well as anterior, superior, and posterior borders. The between the two. The condylar process is subdivided comes to lie near or on the superior border. The angle
remaining border of the ramus depends on an arbitrary into a head and neck. of the mandible is more obtuse in the infant than after
decision as to the dividing line between the ramus and it has become fully developed. Again, in the edentulous
the body; the angle of the mandible is the area of junction The left and right halves typically fuse by the second state, it appears more obtuse, although this may be at
of the posterior and inferior borders of the mandible. year. The position of the mental foramen indicates least in part due to a backward tilt of the condylar
It is usually slightly obtuse in the young adult and flares changes that occur over time. At birth it is near the process.
slightly laterally. In the center of the medial surface of mandible’s inferior border because the alveolar process
the ramus is the mandibular foramen, the beginning of
the mandibular canal that transmits the inferior alveolar
nerve, artery, and vein. The lingula projects partly over
the foramen from its anterior edge, and the mylohyoid

72 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 2-4  Mouth and Pharynx

Lateral view
Joint capsule
Lateral (temporomandibular) ligament
Sphenomandibular ligament
Sphenomandibular ligament (phantom)
Styloid process
Stylomandibular ligament
Mandibular nerve
and otic ganglion

Temporomandibular Joint Joint capsule Medial view
Middle meningeal
The bony structures that enter into the formation of artery
this joint are the head of the mandibular condyle and the Auriculotemporal nerve
mandibular fossa and articular tubercle of the temporal
bone above. The head of the mandible is ellipsoidal, Maxillary artery
with the long axis directed medially and slightly poste- Inferior alveolar nerve
riorly. This articular surface is markedly convex in the
sagittal and coronal planes. The articular surface on the Lingual nerve
temporal bone is concave posteriorly but becomes more Sphenomandibular ligament
convex anteriorly. A fibrocartilage articular disk is inter-
posed between the two articular surfaces just described. Stylomandibular ligament
Each surface of the disk more or less conforms to the Mylohyoid branch of
articular surface to which it is related, but the shape of inferior alveolar artery
the disk between individuals is quite variable. The car- and mylohyoid nerve
tilage that covers the bony articular surfaces differs
from that of most joints in that it is constituted from Mandibular fossa
fibrocartilage tissue rather than hyaline cartilage,
although its gross appearance is similar to that of the Articular disc
articular cartilages of other joints. Articular tubercle

The temporomandibular joint is a true, or synovial, Joint capsule
joint, with two synovial spaces, one superior to the
articular disk and one inferior to it. This joint can be Jaws closed
further described as having a hinge motion in the lower
space and a sliding motion in the upper space. Jaws slightly Jaws widely
opened opened
The capsular ligament is rather loosely arranged, (hinge action (hinge and gliding
being attached superiorly to the margin of the articular predominates) actions combined)
surface on the temporal bone and affixed inferiorly
around the neck of the mandible. The capsular liga- The basic movements that are allowed in the tem- involved, with the hinge movement predominating in
ment is firmly attached to the entire circumference of poromandibular joint are (1) gliding of the articular disk slight opening and the gliding movement predominat-
the articular disk. Forming a pronounced thickening of anteriorly and posteriorly on the articular surface of the ing in wide opening. When chewing, one condyle
the lateral aspect of the capsule is the lateral temporo- temporal bone, accompanied by the head of the man- remains more or less in position, while the other moves
mandibular ligament, which runs inferiorly and posteri- dible (which moves with the disk because the disk is backward and forward. This is combined with slight
orly from the inferior border of the zygomatic process attached near the joint capsule’s attachment to the neck elevation and depression of the mandible. If the mouth
of the temporal bone to the lateral and posterior sides of the mandible and the external pterygoid muscle is is opened just enough so that the upper and lower
of the neck of the mandible. Two accessory ligaments attached to both) and (2) the hinge movement that takes incisor teeth can clear each other, the jaw can be pro-
are not blended with the capsule. The rather thin sphe- place between the head of the mandible and the articu- tracted and retracted, with the movement occurring in
nomandibular ligament runs from the spine of the sphe- lar disk. In opening of the mouth, both movements are the upper joint.
noid bone to the lingula of the mandible, and the
stylomandibular ligament, a thickened band of deep cer-
vical fascia, runs from the styloid process to the lower
part of the posterior border of the ramus of the
mandible.

The temporomandibular joint receives its nerve
supply from the auriculotemporal and masseteric branches
of the mandibular division of the trigeminal nerve. Its
arterial supply comes via branches of the maxillary and
superficial temporal arteries from the external carotid
artery.

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 73

Plate 2-5  Upper Digestive Tract: PART I

Lateral, slightly inferior view

Hyoglossus muscle
Mylohyoid muscle

Digastric muscle (anterior belly) Mastoid
Fibrous loop for intermediate process
digastric tendon
Floor of Mouth Median raphe between Styloid process
mylohyoid muscles
The term floor of the mouth is used differently by differ- Digastric muscle
ent authors, but in all cases it is applied to the floor of Anteroinferior (posterior belly)
the oral cavity proper and does not include the vestibule. view Stylohyoid muscle
It is sometimes used to mean the structures that actually
serve as boundaries of the cavity inferiorly. In this sense, Greater horn Hyoid
the structures that form it would be the superior and Lesser horn bone
lateral surfaces of the anterior part of the tongue and Body
the mucous membrane that is reflected from the side of
the tongue to the inner aspect of the mandible. Other Thyrohyoid muscle
authors have used the term to mean the muscular and
other structures that fill the interval bounded by the Omohyoid muscle
mandible and the hyoid bone. This would mean pri-
marily the mylohyoid muscle, which is then thought of Sternohyoid muscle
as the boundary between the mouth above and the
submandibular triangle of the neck below the muscle. Hyoglossus Median raphe between
muscle mylohyoid muscles
The right and left mylohyoid muscles form a diaphragm Digastric muscle (anterior belly)
that is stretched between the two mylohyoid lines of the Mylohyoid muscle
mandible and the body of the hyoid bone. The posterior Stylohyoid muscle
fibers of each muscle insert on the body of the hyoid Digastric muscle (posterior belly)
bone, and from there forward to the symphysis of the Fibrous loop for intermediate digastric tendon
mandible the right and left muscles meet each other in
a midline raphe. The mylohyoid muscle is supplied by Sublingual gland
the mylohyoid nerve, which is a branch of the inferior
alveolar nerve, which itself is a branch of the mandibular Posterosuperior view Lingual
division of the trigeminal nerve. nerve

Slightly off of the midline, the anterior belly of the Inferior alveolar Lingula
digastric muscle lies along the inferior surface of the nerve and artery Mandibular
mylohyoid muscle. Anteriorly it attaches to the digas- Nerve to mylohyoid foramen
tric fossa of the mandible, and posteriorly it ends in the and artery
intermediate tendon, by means of which it is continuous Submandibular gland
with the posterior belly of the digastric muscle, which and duct (of Wharton)
attaches to the mastoid notch of the temporal bone. The
intermediate tendon is anchored to the hyoid bone by Mylohyoid muscle
a fascial loop. The anterior belly is also supplied by the
mylohyoid nerve and the posterior belly by a branch Geniohyoid muscle Lesser horn Superior mental spine
from the facial nerve. Hyoid bone Body (genial tubercle) for origin
Greater horn of genioglossus muscle
Closely related to the posterior belly of the digastric
muscle, the stylohyoid muscle extends from near the root the floor of the mouth quite mobile. All of these muscles Hyoglossus
of the styloid process to the greater horn of the hyoid can help in the elevation of the hyoid bone and the floor muscle (cut)
bone. It usually attaches to the hyoid by two slips, of the mouth. The geniohyoid and stylohyoid muscles
between which the posterior belly and intermediate determine the anteroposterior position of the hyoid A usage of the term floor of the mouth which is less
tendon of the digastric muscle pass. The stylohyoid is bone, lengthening and shortening the floor of the technical than the two previously given is to think of
supplied by a branch of the facial nerve. mouth. The infrahyoid (strap) muscles (omohyoid, ster- the structure as the mucous membrane that is reflected
nohyoid, sternothyroid, and thyrohyoid) pull the hyoid from the side of the tongue to the mandible. The
The right and left geniohyoid muscles, one on each bone and floor of the mouth inferiorly. attachment of the mucous membrane of this area to the
side of the midline, rest on the superior surface of mandible, where it is continuous with the gum, is along
the mylohyoid muscle. They are attached anteriorly to a line drawn from the posterior end of the mylohyoid
the mental spines and posteriorly to the body of the line to a point just above the mental spine.
hyoid bone. The geniohyoid muscle is supplied by
fibers from the first cervical nerve that accompanies the
hypoglossal nerve.

With the foregoing description of the related muscles
in mind, the hyoid bone can be thought of as held in a
muscular sling hung between the mandible and the
stylomastoid region of the temporal bone, thus making

74 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 2-6  Mouth and Pharynx

Incisive papilla Incisive fossa

Transverse palatine Greater palatine
folds artery and nerve

Palatine raphe Greater palatine
foramen

Palatine process Lesser palatine
of maxilla foramen
Palatine glands Lesser palatine
artery and nerves

Roof of Mouth Horizontal Tendon of tensor
plate of veli palatini muscle
palatine Pterygoid hamulus
bone

The roof of the mouth, or palate, forms the superior Palatine Interdigitating
and posterosuperior boundaries of the “oral cavity aponeurosis fibers of levator
proper,” which it separates from the nasal cavity and (from tensor veli palatini muscle
nasopharynx. The region of approximately the anterior veli palatini Buccinator muscle
two thirds of the palate has a bony framework and is, muscle) Pterygomandibular
therefore, the hard palate; the posterior third is the soft Uvular raphe
palate. The palate is variably arched both anteroposte- muscle
riorly and transversely, the transverse curve being more
pronounced in the hard palate.
Molar minor Superior pharyngeal
The bony framework of the hard palate is formed by salivary glands constrictor muscle
the palatine processes of the two maxillae and the hori-
zontal processes of the two palatine bones that meet in Palatopharyngeus
the midline. These bony structures also form the floor muscle Palatoglossus muscle

of the nasal cavity, and this common bony wall is tra-
versed near the midline anteriorly by the incisive canals,
which transmit blood vessels and nerves between the Palatine
mucous membrane of the nose and the mucous mem- tonsil

brane of the palate. In a posterolateral position at each Anterior view Basilar part of
side of the bony palate are the greater and lesser palatine occipital bone

foramina for the transmission of the greater and lesser Cartilaginous part
palatine vessels and nerves. The oral surface of the bony of pharyngo-
palate is covered by mucoperiosteum (mucous mem- tympanic (auditory,
brane and periosteum fused together), which exhibits a eustachian) tube
faint midline ridge, the palatine raphe, at the anterior
end of which is a slight elevation called the incisive Levator veli palatini muscle (cut) Pharyngobasilar
papilla. Running laterally from the anterior part of the fascia
raphe are about six transverse ridges, the transverse Tensor veli palatini muscle Levator veli
palatini muscle
plicae. Medial pterygoid muscle (cut)
Anteriorly, the soft palate is continuous with the hard
palate and ends posteroinferiorly in a free margin, Choanae
which forms an arch, with the palatoglossal and palato- Medial pterygoid plate Pterygoid hamulus
pharyngeal folds on each side as its pillars. The uvula, Pterygoid hamulus
greatly variable as to length and shape, is a projection
that hangs inferiorly from the free margin of the soft Tendon of tensor veli palatini muscle Superior pharyngeal
palate on the midline. The framework of the soft palate constrictor muscle (cut)

is formed by a strong, thin, fibrous sheet, known as the Levator veli palatini muscle (cut) Palatopharyngeus
palatine aponeurosis, which is partially formed by the Palatopharyngeus muscle (cut) muscle
tendons of the tensor veli palatini muscles. In addition to
the aponeurosis, the thickness of the soft palate is made
up of the palatine muscles, many mucous glands on the Uvular muscle

oral side, and a mucous membrane on both the oral
and pharyngeal surfaces. The mass of glands extends
forward onto the hard palate as far anteriorly as a line Posterior view

between the canine teeth.
The muscles of the soft palate can be briefly described
as follows: (1) the levator veli palatini arises from the pterygoid hamulus, which acts as a pulley, and then accessory nerve, except for the tensor veli palatini,
posteromedial side of the cartilaginous portion of spreads out into the palatine aponeurosis; (3) the uvular which is supplied by the mandibular branch of the tri-
the auditory tube and the adjacent inferior surface of muscle arises from the posterior nasal spine and palatine geminal nerve.
the petrous portion of the temporal bone. Its anterior aponeurosis, and unites with its counterpart on the By means of the actions of the described muscles, the
fibers insert in the palatine aponeurosis, and the poste- other side to end in the mucous membrane of the uvula; soft palate can be positioned as necessary for swallow-
rior ones are continuous with those of the opposite side; (4) the palatoglossus muscle runs from the soft palate to ing, breathing, and phonation. It can be brought into
(2) the tensor veli palatini arises from the anterolateral the side of the tongue; and (5) the palatopharyngeus contact with the dorsum of the tongue and it can be
side of the cartilaginous portion of the auditory tube muscle runs from the soft palate inferiorly into the pha- brought up against the wall of the pharynx, which is
and the adjacent angular spine and the scaphoid fossa ryngeal wall. These muscles are supplied by vagus nerve important in closing off the nasopharynx from the oro-
of the sphenoid bone. Its tendon passes around the fibers, probably from the cranial part of the spinal pharynx during swallowing.

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 75

Plate 2-7  Upper Digestive Tract: PART I

LATERAL VIEWS

Temporalis muscle

Temporal fascia

Muscles Involved in Levator labii Superficial
Mastication superioris alaeque layer
nasi muscle Deep layer
Chewing, or mastication, is one of the important func- Levator labii Zygomatic
tions carried on in the mouth, and a number of muscles superioris muscle arch
are involved either directly or indirectly in this activity. Zygomaticus
However, the four muscles that are primarily respon- minor muscle Articular disc of
sible for the forceful chewing movements of the man- Zygomaticus temporoman-
dible are classified by most authors as the “muscles of major muscle dibular joint
mastication.” These are the masseter, temporalis, lateral Levator anguli
pterygoid, and medial pterygoid muscles. oris muscle Deep part Masseter
Orbicularis Superficial part muscle
The masseter muscle is a thick, quadrangular muscle oris muscle
that is readily palpable on the side of the jaw. It is Mentalis Parotid duct (of Stensen)
described as having a superficial and a deep part, which muscle
can be rather easily separated on the posterior aspect of Depressor labii Buccinator muscle
the muscle but are blended together anteriorly. The inferioris muscle Depressor anguli
superficial part arises from the inferior border of the oris muscle
anterior two thirds of the zygomatic arch (zygomatic Temporalis muscle
process of maxilla, zygomatic bone, and zygomatic Insertion of temporalis muscle to Lateral pterygoid
process of temporal bone) and runs medially and a little coronoid process and anterior muscle
posteriorly to insert on the lateral surface of the lower ramus of andible Masseteric nerve
part of the ramus of the mandible. The area of insertion and artery
continues to the inferior border of the mandible. The Parotid duct (of Stensen) Maxillary artery
deep portion of the masseter muscle arises from the inner Buccinator muscle Insertion of
surface of the whole length of the zygomatic arch and masseter muscle
runs almost vertically inferiorly to insert on the lateral Orbicularis oris muscle
surface of the coronoid process and upper part of the The medial pterygoid muscle, located medial to the
ramus of the mandible. The deepest fibers frequently The superior head attaches to the infratemporal surface ramus of the mandible, is thick and quadrangular. Its
blend with the adjacent portion of the temporalis of the greater wing of the sphenoid bone, and the infe- main origin is from the medial surface of the lateral
muscle. The masseter muscle is supplied by a masseteric rior head attaches to the lateral surface of the lateral pterygoid plate and from the pyramidal process of the
branch from the mandibular division of the trigeminal pterygoid plate. The two heads join and form a tendon palatine bone between the two pterygoid plates. A small
nerve, which reaches the deep surface of the muscle by of insertion that ends on the front of the condylar neck slip of muscle originates from the tuberosity of the
passing through the mandibular notch. of the mandible and on the anterior aspect of the maxilla and the adjacent surface of the pyramidal
capsule and articular disk of the temporomandibular process of the palatine bone. The medial pterygoid
The temporalis muscle, spread out broadly on the joint. A lateral pterygoid nerve from the mandibular muscle inserts on the medial surface of the ramus of the
lateral side of the skull, is a thin sheet, except where its branch of the trigeminal enters the deep surface of this mandible between the mylohyoid groove and the angle.
fibers converge toward the tendon of insertion. It arises muscle.
from the whole temporal fossa (the extensive area
between the inferior temporal line and the infratempo-
ral crest) and from the inner surface of the temporal
fascia that covers the muscle. The temporalis muscle
inserts by means of a thick tendon that passes medial to
the zygomatic arch and attaches to the apex and deep
surface of the coronoid process of the mandible and the
anterior border of the ramus almost as far as the last
molar tooth, with some of the fibers frequently becom-
ing continuous with the buccinator muscle. Two or
three deep temporal branches of the mandibular nerve
enter the deep surface of the temporalis muscle.

The lateral pterygoid muscle is somewhat conical in
shape and runs horizontally in the infratemporal fossa.
It arises as the fusion of superior and inferior heads.

76 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 2-8  Mouth and Pharynx

LATERAL AND POSTERIOR VIEWS

Articular disc of
temporomandibular joint
Articular tubercle
Lateral pterygoid muscle
(superior and inferior heads)
Sphenomandibular ligament
Medial pterygoid muscle
Parotid duct (of Stensen)
Buccinator muscle

Muscles Involved in Pterygomandibular raphe
Mastication (Continued) Superior pharyngeal
constrictor muscle
The medial pterygoid nerve from the mandibular runs
along the medial side of the muscle to enter it. Lateral view

The muscles of mastication all pass across the tem- Sphenomandibular Internal Choanae Cartilaginous part of pharyngotympanic
poromandibular joint, and they are the major muscles Middle ligament carotid (auditory, eustachian) tube
producing the movements allowed at this joint. Eleva- meningeal Otic artery
tion of the mandible is brought about by the masseter, Masseteric ganglion
temporalis, and medial pterygoid. They are able to artery nerve
bring the lower teeth powerfully up against the upper
teeth. They also are acting against gravity in most posi- Auriculo- Temporo-
tions of the head in keeping the mouth closed. If they temporal mandibular
are relaxed, the weight of the jaw can gap the mouth to nerve joint
a small degree. The muscle of mastication that actively Foramen ovale
opens the mouth is the lateral pterygoid. It does this by Masseteric artery Lateral pterygoid
pulling the articular disk and condyle of the mandible Medial muscle (superior
anteriorly. Other muscles that help in opening the pterygoid nerve and inferior heads)
mouth against resistance are the suprahyoid, infrahy- Maxillary artery Lateral pterygoid
oid, and platysma muscles. Protrusion of the jaw is plate
brought about primarily by bilateral contraction of the Inferior Medial pterygoid
lateral pterygoid, because in this movement, also, the alveolar nerve muscle
articular disk and condyle of the mandible are brought Lingual nerve
anteriorly. The superficial portion of the masseter and Medial Tensor veli palatini
the medial pterygoid can give some minor aid in protru- pterygoid muscle muscle (cut)
sion. Retraction of the mandible is accomplished mostly Medial Levator veli palatini
by the posterior part of the temporalis muscle, some of pterygoid plate muscle (cut)
the fibers of which run nearly horizontally. The digas- Pterygoid hamulus Pterygoid hamulus
tric and geniohyoid muscles can contribute to retrac-
tion when the hyoid bone is anchored. Nerve to mylohyoid

All the muscles of mastication are employed in the Posterior view
act of chewing, because it involves the four movements
of the mandible described above (i.e., elevation, depres- its origin from the outer surfaces of the maxilla and the corner of the mouth, so that the superior fibers
sion, protrusion, and retraction) and at least one of the mandible in the region of the molar teeth and between of this intermediate group go into the lower lip and
muscles of mastication is involved in each of these the posterior ends of these lines of attachment from the the inferior fibers of the intermediate group go into
movements. For the most part, chewing is done either pterygomandibular raphe, by means of which it is con- the upper lip. The buccinator muscle is supplied by the
on one side or the other, and the condyle of the side on tinuous with the superior constrictor of the pharynx. facial nerve. The framework of the lips is formed by the
which the chewing is being done remains more or less From this U-shaped origin, the horizontal fibers of the orbicularis oris muscle. In addition to the fibers that
in position while the condyle of the other side moves muscle run anteriorly, apparently to continue into the appear to be the forward prolongations of the buccina-
back and forth, as in protrusion and retraction. This orbicularis oris muscle, with the superiormost and inferi- tor muscle, fibers come into the orbicularis oris from
is combined in proper sequence with slight elevation ormost fibers going into the upper and lower lips, all of the muscles that insert in the vicinity. The orbi-
and depression to bring about the grinding action on respectively, and the intermediate fibers crossing near cularis oris muscle is also supplied by the facial nerve.
the food.

In order that grinding can be carried on efficiently,
the food must be kept between the teeth by the tongue
on one side and the cheek and lips on the other side.
Naturally, the muscular framework of the cheek and lips
is important in accomplishing this. The framework of
the cheek is formed by the buccinator muscle, which takes

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 77

Plate 2-9  Upper Digestive Tract: PART I

DORSUM OF TONGUE AND SCHEMATIC STEREOGRAM

Epiglottis

Median glossoepiglottic fold

Lateral glossoepiglottic fold

Vallecula

Tongue Palatopharyngeal arch and muscle (cut)
Palatine tonsil (cut)

Root Lingual tonsil (lingual nodules)
The tongue is an extremely mobile mass of striated Palatoglossal arch and muscle (cut)

muscle, covered by mucous membrane. Arising from Foramen cecum
the floor of the mouth, the tongue practically fills the
oral cavity when all its parts are at rest and the indi- Terminal sulcus
vidual is in an upright position. The shape of the tongue Vallate papillae

may change extensively and rapidly during the various Foliate papillae
activities it has to perform.
The areas of the tongue covered by the mucous
membrane are the apex, the dorsum, the right and left
margins, and the inferior surface. These are obvious Filiform papillae

topographic designations, except for the dorsum, which Body
needs further description. The dorsal aspect of the
tongue extends from the apex to the reflection of the
mucous membrane to the anterior surface of the epiglot- Fungiform papilla
tis at the vallecula, forming an arch that, in its anterior
Midline groove (median sulcus)

or palatine two thirds, is directed superiorly, whereas
its posterior or pharyngeal one third is directed poste-
riorly. Several divisions of the tongue have been pro- Dorsum of tongue

posed. Sometimes the terminal sulcus has been said to
separate the body and the root of the tongue, but in other Apex
instances the portion called the root has been limited Lingual tonsil
to the posterior and inferior attachment of the tongue
or has even been restricted to mean only the region of
attachment through which muscles and other structures
enter and leave the tongue. From the practical point of
view, it is rather irrelevant where one permits the root Filiform
to start and the body to end, or vice versa, but it is papillae
important to realize that the posterior third of the
tongue and its epiglottic region are not visible by simple Fungiform
inspection even if the tongue is protruded unless the papilla

examiner uses a mirror or presses the tongue down with Keratinized
the aid of a spatula. tip of papilla
At the posterior end of the body is a small blind pit,
known as the foramen cecum, the remnant of the thyro-
glossal duct, from which the thyroid gland developed
during the fetal stage. Angling anterolaterally toward Intrinsic muscle

each side from the foramen cecum is the terminal
sulcus, which is usually referred to as the dividing line
between the anterior and posterior parts of the tongue. Duct of
However, the real dividing line may run just anterior to Crypt gland
the vallate papillae. A median sulcus is not always very Lymph follicles
distinct but is related to the interior, lingual septum. Mucous glands

The mucous membrane covering the apex and body Vallate papilla

of the tongue is moist and pink and is thickly studded Taste buds

with various papillae. The majority of the papillae are Furrow
of the filiform type, in which the epithelium ends in
tapered, rough points to provide friction for the han- Lingual glands (serous glands of von Ebner)

dling of food. Scattered about the field of filiform papil- Schematic stereogram: area indicated above
lae are the larger, rounded fungiform papillae. In front
of the sulcus terminalis runs a V-shaped row of 8 to 12
(circum) vallate papillae, which rise far more promi-
nently over the surface of the mucous membrane than The lymphoid nodules are grouped around the The mucous membrane of the inferior surface of the
do the two other types of papillae. The whole mucosa epithelium-lined crypt or pit and, taken collectively, are tongue is thin, smooth, devoid of papillae, and more
of the anterior two thirds of the tongue is firmly adher- called the lingual tonsil. loosely attached to the underlying tissue. It exhibits the
ent to the underlying tissue. On both margins of the tongue, the mucous mem- midline frenulum and some rather rudimentary fimbri-
The mucous membrane of the posterior one third of brane is thinner and, for the most part, devoid of papil- ated folds that run posterolaterally from the tip of the
the tongue (the pharyngeal part), though smooth and lae, though a variable number of vertical folds may be tongue. The frenulum is a duplication of the mucous
glistening, has an uneven or nodular surface owing to found on the posterior part of each margin. They are membrane and connects the inferior lingual surface
the presence of a varying number (35 to 100) of rounded called foliate papillae, and represent rudimentary struc- with the floor of the mouth. The deep lingual veins
elevations with a crypt in the center. These nodules tures similar to the well-developed foliate papillae seen usually shine through the mucosa between the frenu-
consist of lymphoid tissue lying deep to the epithelium. in rodents. lum and the fimbriated folds on each side.

78 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 2-10  Mouth and Pharynx

LATERAL VIEWS

Palatopharyngeus muscle
Palatoglossus muscle
Inferior longitudinal muscle of tongue

Mastoid process

Tongue (Continued) Digastric muscle
(posterior belly)(cut)
Styloid process

Pharyngobasilar fascia
Superior pharyngeal
Many small glands are scattered beneath the mucous constrictor muscle
membrane and partly embedded in the muscle. Mucous Stylohyoid ligament
glands are located in the posterior third of the dorsum, Styloglossus muscle
with their ducts opening on the surface and into the pits
of the lingual tonsil. In the region of the vallate papillae,
the purely serous lingual glands of von Ebner send numer- Glossopharyngeal part of
ous ducts (from 4 to 38) into the furrows, or moat, superior pharyngeal constrictor
surrounding each of these papillae. Glands of a mixed
type, the lingual glands of Blandin and Nuhn, are found Genioglossus muscle Stylopharyngeus muscle
to each side of the midline inferior and posterior to the Mylohyoid muscle (cut) Stylohyoid muscle
apex of the tongue. Geniohyoid muscle Middle pharyngeal
constrictor muscle
The receptor organs for the sense of taste, the taste Digastric muscle (posterior belly) (cut)
buds, are pale oval bodies (about 70 µ in their long axis), Hyoglossus muscle
seen microscopically in the epithelium of the tongue Intermediate tendon of digastric muscle (cut)
and to a much lesser extent in the epithelium of the soft
palate, pharynx, and epiglottis. The taste buds are most Hyoid bone
prevalent in the epithelial lining of the furrows sur- Fibrous loop for intermediate digastric tendon

rounding the vallate papillae. A few taste buds are
present on the fungiform papillae and also scattered on
the foliate papillae. A taste bud reaches from the base-
ment membrane to the epithelial surface, where a pore Lateral view

is situated, into which the microvilli (taste hairs) of the Lingual nerve Superior pharyngeal
neuroepithelial taste (gustatory) cells extend. From 4 to constrictor muscle

20 taste cells are intermingled with the more numerous Submandibular ganglion Styloglossus muscle
supporting sustentacular cells of the taste buds. Deep lingual
artery Palatoglossus muscle (cut)
The majority of the tongue is made up of skeletal and venae Stylohyoid ligament
(striated) muscles, which are composed of muscular comitantes Stylopharyngeus muscle
bundles, interlaced in many directions. An incomplete Hyoglossus muscle (cut)
lingual septum divides the tongue into symmetric halves. Artery to Lingual artery
One group of muscles, the extrinsic ones, originates frenulum
outside of the tongue, whereas the intrinsic group of Submandibular External carotid artery
lingual muscles originates and inserts entirely within duct (of
other muscles of the tongue. The genioglossus muscle Wharton) Internal jugular vein
arises from the superior mental spine of the mandible Retromandibular vein
and fans out along the entire length of the dorsum of
the tongue, with the lowest fibers having some attach-
ment to the hyoid bone. Lateral to this muscle is the
hyoglossus muscle, which arises from the body of the
hyoid bone as well as the entire length of the greater Facial vein

and lesser horns from which it runs vertically upward. Common trunk for
The styloglossus muscle arises from near the tip of the facial, retromandibular,
styloid process and an adjacent part of the styloman- Genioglossus muscle Lingual vein and lingual veins
dibular ligament. It runs as a band inferiorly and Sublingual artery and vein Suprahyoid artery (common facial vein)
anteriorly onto the lateral aspect of the tongue. The
Geniohyoid muscle Hyoid bone Dorsal lingual artery and vein

palatoglossus muscle descends from the soft palate, Hypoglossal nerve (XII) Vena comitans of hypoglossal nerve
forming the framework of the palatoglossal fold. The
intrinsic lingual muscles are named according to the
three spatial dimensions in which their fascicles run. Of
the two longitudinal muscles, the superior longitudinal
band extends from anterior to posterior just deep to The vertical lingual muscle is made up of all the vertical the palatoglossus muscle, which is innervated by the
the mucous membrane of the dorsum. The inferior fibers, except those supplied by extrinsic muscles, with vagus nerve; (2) general sensory to the anterior two
longitudinal band spreads between the genioglossus and which it forms a closely woven network. By the com- thirds via the lingual nerve, which is accompanied by
hyoglossus muscles on the undersurface of the tongue. bined actions of all these muscles, the shape of the the chorda tympani, a branch of the facial nerve, which
The contraction of both longitudinal muscles short- tongue can be extensively altered: lengthened, short- is special sensory (taste) to the same area; and (3) glos-
ens the tongue. The transverse lingual muscle, which is ened, broadened, narrowed, curved in various direc- sopharyngeal nerve, which is general and special sensory
covered by the superior longitudinal muscle, furnishes tions, protruded, and drawn back into the mouth. to the posterior one third of the tongue. The vagus
nearly all of the transversely running fibers and is inter- The innervation of the tongue involves the following nerve is general and special sensory to the epiglottic
mingled with fascicles of the extrinsic muscle group. nerves: (1) motor from the hypoglossal nerve except for region.

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 79

Plate 2-11  Upper Digestive Tract: PART I

Teeth Deciduous DECIDUOUS AND PERMANENT TEETH Permanent
(primary) (colored blue)
The teeth are specialized structures that bite or tear off Usual age of Central incisors Usual age of
the pieces of solid food that enter the oral cavity and eruption Lateral incisors
chop and grind this food as it is being mixed with saliva eruption
in preparation for swallowing. The muscles of mastica- Central incisor Canines
tion are responsible for the movements of the lower (8–10 months) 1st premolars Central incisor
teeth in relation to the upper teeth, and the tongue and Lateral incisor 2nd premolars (7th year)
cheeks are responsible for positioning food between the (8–10 months) Lateral incisor
teeth as necessary. Canine (cuspid) 1st molars (8th year)
(16–20 months) 2nd molars Canine (cuspid)
Humans develop two sets of teeth, a deciduous set 1st molar 3rd molars (11th–12th year)
(milk teeth), which begin to come in at about the age (15–21 months) 1st premolar
of 6 months, and a so-called permanent set, which 2nd molar (9th year)
gradually begin to replace the deciduous set at about (20–24 months) 2nd premolar
the age of 6 years. 2nd molar (10th year)
(20–24 months) 1st molar
The deciduous teeth number 20 in all, 5 on each side 1st molar (6th year)
of the upper and lower jaws. Starting at the midline of (15–21 months) 2nd molar
each jaw and progressing laterally and posteriorly to Canine (cuspid) (12th–13th year)
each side, the deciduous teeth are named in order: (16–20 months)
central (medial) incisor, lateral incisor, canine (cuspid), Lateral incisor 3rd molars
first molar, and second molar. The four teeth of the same (15–21 months) (17th–25th year)
name are differentiated by designating which jaw and Central
which side of the jaw, as right or left upper (maxillary) incisor (6–9 2nd molar
or lower (mandibular) central incisor. The deciduous months) (12th–13th year)
teeth are smaller than the permanent teeth that take 1st molar
their position. Incisive fossa (6th year)
Palatine process 2nd premolar
The permanent teeth, once all have come in, number of maxilla (10th year)
32, 8 on each side of the upper and lower jaws. Starting Horizontal 1st premolar
at the midline of each jaw and progressing laterally and plate of (9th year)
posteriorly to each side, the permanent teeth are named palatine Canine (cuspid)
in order: central (medial) incisor, lateral incisor, canine bone (11th–12th year)
(cuspid), first premolar (bicuspid), second premolar (bicus-
pid), first molar, second molar, and third molar (wisdom Lateral incisor
tooth). The incisors, and to some extent the canines, (8th year)
are adapted for biting the food, whereas the molars, and Central incisor
to some extent the premolars, are adapted for grinding (7th year)
and pounding food.
Greater and lesser Lower permanent teeth
Normally, the upper dental arch is wider than the palatine foramina
lower dental arch, and the upper incisors and canines Upper permanent teeth
overlap the lower incisors and canines. When the jaws
are closed (in occlusion), the teeth of the two jaws come this be recognized as a permanent tooth and given the present within the jaw long before they erupt. Obvi-
into contact in such a way that their chewing surfaces care that a permanent tooth merits. Starting in the ously, during the eruption of the teeth, growth changes
fit each other, which means that the teeth of one jaw seventh year, gradual replacement of the deciduous must occur in the jaws.
are not exactly opposite the corresponding teeth of the teeth by the permanent teeth takes place, which is
other jaw. In spite of this, because the lower molars, usually completed by the twelfth year. The second The crown of a tooth is the portion of the tooth
especially the third molars, are longer anteroposteri- molar, as a rule, emerges about this time, and the third projecting beyond the gum. It differs in shape in differ-
orly, the dental arches end at approximately the same molar, if it erupts at all, several years later. The approxi- ent types of teeth, the difference being related to the
place posteriorly. Teeth are described as having a labial mate time at which each permanent tooth may erupt is functional adaptation of the tooth. The crown of an
(buccal) surface, a lingual surface, and a contact surface. specified in the accompanying illustration below the incisor is chisel shaped, that of a canine is large and
name of the tooth. The developing permanent teeth are more conical, and the crowns of the premolars and
Ordinarily, none of the teeth have erupted before molars are flattened and broad, with tubercles.
birth, but all of the deciduous teeth usually come in
between the sixth month and the end of the second year.
The time of eruption varies considerably as does any
timetable of development. The possible range of the
time at which each deciduous tooth may erupt is indi-
cated in the parentheses below the name of each tooth
in the accompanying illustration.

From the end of the second year until the sixth year,
no visible change in the teeth takes place. At about the
sixth year, the first permanent molar comes in posterior
to the second deciduous molar, and it is important that

80 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 2-12  Mouth and Pharynx

DETAILED ANATOMY

Teeth (Continued) Crown Enamel
Neck Dentine and
The neck of a tooth is the short, constricted portion Root dentinal tubules
that connects the crown and the root. Interglobular spaces
Odontoblast layer
The root of a tooth is the portion embedded in the Interproximal spaces
alveolar process of the jaw. It is long, tapering, and Dental pulp
fitted to its socket. The root of an incisor is usually containing vessels
single, the canine has a single long root, and that of a and nerves
premolar is usually single, flattened anteroposteriorly, Papilla
and grooved, with some tendency to division. Each Gingival (gum)
molar has two roots, an anterior root and a posterior epithelium (stratified)
root, which are apt to be wide, flattened anteroposteri- Lamina propria of
orly, grooved, and perhaps partially divided. At the tip gingiva (gum)
(or tips) of each root is a minute opening called the (mandibular or
apical foramen, which allows passage for blood vessels maxillary
and nerves to the root. periosteum)
Gingival groove
The interior of a tooth contains a space called the Periodontal
cavity of the tooth (pulp cavity), which is filled in the ligament
natural state by loose connective tissue, capillaries,
nerves, and lymphatics, collectively called the pulp, on Cement
the outer surface of which is a layer of cells called odon-
toblasts. The cavity extends into each root as the taper- Root (central)
ing root canal, which ends at the apical foramen. canals containing
vessels and nerves
Surrounding the cavity is the dentin, which consti-
tutes the mass of the tooth and is a hard, highly calcified Bone
(only 28% organic matter), homogeneous material. It
is traversed by dentinal tubules (dental canaliculi) extend- Apical foramina
ing from the cavity to the outer margin of the dentin.
The dentinal tubules are occupied by processes of the Left upper
odontoblasts, which create the dentin. permanent
teeth:
Forming a cap over the dentin of the crown is the labiobuccal
dense, white, and glistening enamel, the hardest (only view
about 3% organic material) and most resistant material
in the body. It is made up of solid, hexagonal prisms Left lower Lateral 12 12 3
(enamel prisms), which are oriented essentially perpen- permanent Premolars
dicular to the related surface of the crown. It is created teeth:
within the gums by cells called ameloblasts. labiobuccal
view
Cementum, modified bone having lamellae, canaliculi,
and lacunae, covers the dentin of the roots. It is very Central
thin at its beginning at the neck and increases in thick-
ness toward the root’s apex. Incisors Canines Molars
(cuspids)
The root of the tooth is united to the wall of the
socket by an important layer of vascular fibrous connec- which surrounds the base of the crown of the tooth for The enamel of the tooth originates from the oral
tive tissue, the alveolar periosteum or periodontal liga- a short distance like a collar. ectoderm, which differentiates into ameloblasts, and
ment. This layer is continuous with the lamina propria the rest of the tooth comes from the mesenchymal
of the gum at the alveolar process margin (near the neck The arteries and nerves that supply the teeth are tissue of the maxillary and mandibular arches. The
of the tooth). branches of the superior and inferior alveolar arteries ameloblasts and odontoblasts create a bell-shaped
and nerves. These travel partly to the pulp cavity structure as they lay down enamel and dentin to create
The covering of the internal and external surfaces of and partly to the surrounding periodontal ligament. the tooth within the mesenchyme. The mesenchyme
the alveolar processes of the maxilla and mandible, the Branches to the pulp cavity travel by way of the apical remains in the dental pulp, allowing the alveolar vessels
gums or gingivae, is made up of stratified squamous epi- foramen and root canal. The vessels form a rich capil- and nerves to reach the developing tissues.
thelium, resting on a thick, strong lamina propria, which lary plexus under the odontoblast layer.
is firmly attached to the underlying bone. This, being
a fusion of mucous membrane and periosteum, could
be called mucoperiosteum. The gum forms a free fold,

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 81

Plate 2-13  Upper Digestive Tract: PART I

Superficial temporal Temporalis tendon
artery and vein and
auriculotemporal nerve

Branches of
facial nerve (VII)

Transverse facial artery
Accessory
parotid gland

Salivary Glands Parotid duct Parotid
Buccinator gland
Numerous glands secrete the watery, somewhat viscous muscle (cut)
fluid known as saliva into the oral cavity. Small salivary Masseter Retroman-
glands are widely scattered under the lining of the oral muscle dibular vein
cavity and are named, according to their location, labial, Lingual nerve (anterior
buccal, palatine, and lingual glands. The three chief, large, Submandibular and
paired salivary glands are the parotid, submandibular, ganglion posterior
and sublingual. divisions)
Tongue Digastric muscle
The parotid gland, the largest of the salivary glands, Frenulum of (posterior belly)
is roughly shaped as a three-sided wedge, which is fitted tongue External jugular vein
in anterior and inferior to the external ear. The trian- Sublingual fold with Sternocleidomastoid
gular superficial surface of the wedge is practically sub- openings of muscle
cutaneous, with one side of the triangle almost as high sublingual ducts Stylohyoid muscle
as the zygomatic arch and the opposing angle at the (of Rivinus) Common trunk receiving
level of the angle of the mandible. The anteromedial facial, anterior branch of
side of the wedge abuts against and overlaps the ramus Sublingual caruncle retromandibular, and
of the mandible and the related masseter and medial with opening of lingual veins (common
pterygoid muscles. The posteromedial side of the submandibular facial vein)
wedge turns toward the external auditory canal, mastoid duct
process, sternocleidomastoid, and digastric (posterior
belly) muscles. The parotid (Stensen) duct leaves the Sublingual gland
anterior border of the gland and passes superficial to
the masseter muscle, at the anterior border of which it Submandibular
turns medially to pierce the buccinator muscle and then duct
the mucous membrane of the cheek near the second
maxillary molar. Sublingual artery and vein

The submandibular gland lies in the submandibular Mylohyoid muscle (cut)
triangle but overlaps all three sides of the triangle,
extending superficial to the anterior and posterior Digastric muscle (anterior belly)
bellies of the digastric muscle and deep to the mandible,
in the submandibular fossa. Most of the gland is inferior Submandibular gland
to the mylohyoid muscle, but a deep process extends supe- Facial artery and vein Hyoid bone
rior to the muscle. The submandibular (Wharton) duct at
first runs anteriorly with the deep process and then External carotid artery
in close relation to the sublingual gland (first inferior Internal jugular vein
and then medial to it) to reach the sublingual caruncle
at the summit of which it opens, next to the lingual Parotid gland: Submandibular gland: Sublingual gland:
frenulum. totally serous mostly serous, partially mucous almost completely mucous

The sublingual gland, the smallest of the three paired serous demilunes, with different proportions of these in epithelium to portions of the duct system, which are
salivary glands, is located deep to the mucous mem- different glands. The parotid gland is almost entirely thought to contribute water and salts to the secretion
brane of the floor of the mouth, where it produces the serous, the submandibular gland is predominantly and, hence, are called secretory ducts. The epithelium
sublingual fold. It lies superior to the mylohyoid muscle serous but with some mucous alveoli containing serous of the ducts is at first cuboidal, then columnar, and may
in relation with the sublingual fossa on the mandible. demilunes, and the sublingual gland varies to quite an finally be stratified cuboidal near the opening of the
In contrast to the parotid and submandibular glands, extent in composition in different parts of the gland but, duct. It should be noted that the appearance of serous
which have quite definite fibrous capsules, the lobules for the most part, is predominantly mucous with serous demilunes is an artifact of specimen preparation and
of the sublingual gland are loosely held together by demilunes. In the parotid and submandibular glands, that during life, the serous-secreting cells of each acinus
connective tissue. About 12 sublingual ducts leave the the alveoli are joined by intercalated ducts with low sit side by side with the mucous-secreting cells.
superior aspect of the gland and open individually
through the mucous membrane of the sublingual fold.
Some of the ducts from the anterior part of the gland
may combine and empty into the submandibular duct.
This is apparently prone to considerable variation.

The nerve supply of the large salivary glands is dis-
cussed in a later segment on the innervation of the
mouth and pharynx and the autonomic nervous system.

Microscopically, the large salivary glands appear as
compound tubular-alveolar glands. The secretions of
these glands are serous and mucous and mucous with

82 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 2-14  Mouth and Pharynx

Horizontal section Orbicularis oris muscle
below lingula of Buccinator muscle
mandible (superior view)
demonstrating bed Buccopharyngeal fascia
of parotid gland

Facial artery and vein

Pterygomandibular raphe
Lingual nerve and superior
pharyngeal constrictor muscle

Masseter muscle
Palatoglossus muscle in palatoglossal arch

Palatine tonsil
Palatopharyngeus muscle
in palatopharyngeal arch

Sections Through Mouth Ramus of mandible
and Jaw Inferior alveolar artery,
vein, and nerve to mylohyoid
AXIAL SECTION AT ATLAS LEVEL AND
BEHIND FIRST MOLAR Medial pterygoid muscle
The structures illustrated and discussed individually in Styloglossus muscle
the preceding pages are shown in these cross sections,
one axial, the other coronal, in their mutual topo- Facial nerve (VII)
graphic relationships. The cheek is formed essentially
by the buccinator muscle and its fascia, with the skin and Retromandibular vein
its appendages, including fat, glands, and connective
tissue, covering it on the outside and the oral mucosa External carotid artery
on the inside.
Parotid gland
The continuity of the oral and oropharyngeal wall,
as it becomes visible in this cross section, may attain Stylopharyngeus muscle Axis (C2)
some practical significance in abscess formation and Stylohyoid muscle
other pathologic processes. One should realize that the Longus capitis muscle
buccinator muscle is separated only by the small fascial Sternocleidomastoid muscle Prevertebral fascia
structure, the pterygomandibular raphe, from the superior Buccopharyngeal fascia
pharyngeal constrictor muscle, which constitutes the most Digastric muscle (posterior belly) and retropharyngeal space
substantial component of the oropharyngeal wall. The
thin pharyngeal fascia, creating by the looseness of its Internal jugular vein, internal carotid artery,
structure a retropharyngeal space, separates the poste- and nerves IX, X, and XII in carotid sheath
rior wall of the pharynx from the vertebral column and
prevertebral muscles. Superior cervical sympathetic ganglion

The tonsillar bed, as it lies between the palatoglossal Superior longitudinal muscle of
and palatopharyngeal arches, is easier to comprehend in Vertical and transverse muscles tongue
a cross section. Inferior longitudinal muscle
Styloglossus muscle
Supplementing the picture of the external aspect of Buccinator muscle
the parotid gland, the cross section demonstrates the Muscles of facial expression
thin medial margin of the gland and its relation to the Hyoglossus muscle
muscles arising from the styloid process (stylohyoid, sty- Genioglossus muscle
lopharyngeus, and styloglossus muscles), the internal jugular Sublingual salivary gland
vein, and the internal carotid artery. Of further note is Submandibular duct
the closeness of the most medial part of the parotid Mandibular canal, inferior alveolar artery,
gland to the lateral wall of the pharynx and the location vein, and nerve
within the glandular substance of the retromandibular Lingual nerve
vein (beginning above the level of the cross section by Nerve to mylohyoid
the confluence of the superficial temporal and maxillary Vena comitans of hypoglossal nerve
veins), the facial nerve, and the external carotid artery, (to lingual vein)
which latter divides higher up, but still within the gland, Facial artery
into the superficial temporal and maxillary arteries. Lingual artery
Hypoglossal nerve (XII) Coronal section
Submandibular lymph node posterior to 1st
Submandibular salivary gland molar tooth
Facial vein (anterior view)
demonstrating
Mylohyoid muscle beds of sublingual
Intermediate digastric tendon and submandibular
glands
Hyoid bone

CORONAL SECTION

The frontal or coronal section of the tongue brings into mandible, only separated from it at the level of the The mandibular canal harbors the inferior alveolar
view the mutual relationships of its muscular compo- section by the facial artery. On the deep surface of the artery, vein, and nerve. The intermediate tendon of the
nents, particularly the lingual septum dividing the tongue mylohyoid muscle one also finds the posterior end of digastric muscle passes through the fascial loop that
into symmetric halves. The lingual artery courses medial the sublingual salivary gland in a location that would be anchors it to the hyoid bone.
to the genioglossus muscle, whereas the main lingual occupied by the deep process of the submandibular
vein, the hypoglossal and lingual nerves, and the duct of the gland in a section slightly more posteriorly. As the With the two reflections—one from the inferior
submandibular gland lie lateral to the genioglossus and result of the crossings of the lingual nerve and subman- surface of the tongue across the floor of the mouth to
medial to the mylohyoid muscle. Located inferior and dibular duct, the apparent relationship of these two the gum on the inner aspect of the alveolar process of
lateral to the latter muscle is the main body of the structures in the cross section would be reversed if one the mandible, the other from the outer surface of this
submandibular gland. Its lateral margin touches the were to obtain a more anterior section. process to the cheek—the lining of the oral cavity by
the mucous membrane becomes continuous.

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 83

Plate 2-15  Upper Digestive Tract: PART I

Fauces Cartilaginous part of Pharyngeal tonsil Sphenoidal sinus Medial view
pharyngotympanic Pharyngeal tonsil sagittal section
The connotation given to the term fauces varies. Though (auditory, eustachian) tube Torus tubarius
complete agreement exists as to the general region to Pharyngeal tubercle
which the term refers, the precise contents and bound- (basilar part of occipital bone)
aries of this region vary between sources. In general, Pharyngeal raphe
the area covers the space from the oral cavity into the
pharynx. By most authors, the designation isthmus of the Pharyngeal opening of
fauces, or oropharyngeal isthmus, is taken to mean pharyngotympanic
the aperture by which the mouth communicates with (auditory, eustachian) tube
the pharynx (i.e., the dividing line between the oral
cavity and the oropharynx). The boundaries of this Pharyngeal recess
isthmus are the soft palate superiorly, the dorsum of the Salpingopharyngeal fold
tongue in the region of the terminal sulcus inferiorly, Hard palate
and the left and right palatoglossal folds, also known as Soft palate
the anterior pillars of the fauces, which rise archlike on Palatine glands
each side in the posterior limit of the oral cavity. Uvula
Semilunar fold
Closer to the oropharynx, a second arch is formed by Supratonsillar fossa
the palatopharyngeal folds, also called the posterior pillars Palatine tonsil
of the fauces. As a result of the projecting prominence Palatopharyngeal arch
of the anterior and posterior folds on each side, a fossa Oropharynx
(tonsillar fossa or tonsillar sinus) comes into existence, Palatoglossal arch
which houses the palatine tonsil. On the free surface of Triangular fold
this oval mass, which may bulge medially into the cavity Tongue (drawn anteriorly
of the pharynx for varying distances, 12 to 15 orifices and inferiorly)
(fossulae tonsillares) can be recognized. These are the
openings of the tonsillar crypts. The latter branch and Lingual tonsil
extend deeply into the substances of the tonsils. Several Epiglottis
quite variable folds may overlap the medial surface of Vallecula
the tonsils in different degrees. Most frequently found
is a triangular fold located anteriorly and inferiorly to Pharyngeal mucosa removed
the tonsils. Also, between the superior portions of
the palatoglossal and palatopharyngeal folds, one may Medial pterygoid plate
encounter frequently a supratonsillar fold that contains
tonsillar tissue, a fact that has prompted some authors Tensor veli palatini muscle and tendon
to call the recess below this fold the infratonsillar recess Levator veli palatini muscle
(or fossa) and others to designate it as “supratonsillar.”
The lateral surface of the tonsil has a fibrous capsule, Ascending palatine artery
which is separated by some loose connective tissue from
the superior constrictor muscle of the pharynx and, to a Pharyngeal branch of
lesser and variable degree, from the palatopharyngeus ascending pharyngeal artery
muscle that sits deep to the fold of the same name. Lesser palatine artery

The chief blood supply of the tonsil is the tonsillar Salpingopharyngeus muscle
branch of the facial artery, but the tonsillar branches of
the lesser palatine, ascending palatine, ascending pharyngeal, Pterygoid hamulus
and dorsal lingual arteries also participate in the arterial Pterygomandibular raphe

Tonsillar branch of lesser palatine artery

Superior pharyngeal constrictor muscle
Tonsillar branch of
ascending pharyngeal artery
Palatoglossus muscle

Palatopharyngeus muscle

Tonsillar branch of ascending palatine artery
Tonsillar branch of facial artery

Tonsillar branch of dorsal lingual artery

Glossopharyngeal nerve
(IX) and tonsillar branch

Stylohyoid ligament
Hyoglossus muscle
Middle pharyngeal constrictor muscle

Stylopharyngeus muscle

blood supply. Lymphatic fluid from the tonsil drains mostly in the form of lymph nodules or follicles, which,
primarily to the jugulodigastric lymph node of the superior particularly in younger individuals, contain many ger-
deep cervical group. The tonsil is innervated primarily by minal centers. Expansions from the above-mentioned
the glossopharyngeal nerve, though a few branches of the fibrous capsule on the lateral tonsillar surface enter the
lesser palatine nerves also enter the tonsils. lymphoid tissue, forming septa between the follicles
surrounding the adjacent crypts.
A stratified squamous epithelium covers the tonsil
and also lines the crypts, where it may be obscured by Present at birth and increasing in size rapidly during
lymphocyte infiltration. The mass of the tonsils consists the first few years of life, the tonsils usually decrease in
of lymphatic (lymphoid) tissue, which presents itself size about puberty and may become atrophic in old age.

84 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 2-16  Mouth and Pharynx

Section through upper lip (Hematoxylin-eosin, ¥10)

Oral surface Hair shaft
Skin surface
Mucous Sebaceous glands
glands Epidermis
Lamina Corium
propria Orbicularis oris muscle
Artery
Histology of Mouth Submucosa Sebaceous gland
and Pharynx Stratified without hair follicle
squamous Mucocutaneous junction
epithelium
Section through wall of pharynx
The mouth and pharynx are lined by a mucous mem- Duct of gland (Hematoxylin-eosin, x50)
brane that is attached in much of the area to the sup-
porting wall (bone, cartilage, or skeletal muscle) by a Pseudostratified ciliated
fibroelastic, gland-containing submucosa that varies columnar epithelium
greatly in size, looseness, and the distinctness with Mixed glands (nasal)
which it can be delimited from the mucous membrane. Musculature (striated)
The submucosa is interpreted as absent on most of the Mucous glands (oral)
hard palate, the gums, and the dorsum of the tongue. Elastic tissue layer
The mucous membrane is composed of epithelium, Lamina propria
which is predominantly nonkeratinized, stratified, and Stratified squamous epithelium Stratified squamous epithelium

squamous in type, a basement membrane, and the Lamina propria deepest part of this lamina is a definite elastic tissue
fibroelastic lamina propria, which has vascular papillae layer with many longitudinally oriented fibers. A well-
indenting the epithelium to varying degrees in different Elastic tissue layer developed submucosa is present only in the lateral
areas. The muscularis mucosae, which is present in the (pharyngobasilar fascia) extent of the nasopharynx and near the continuity of
the pharynx with the esophagus. Scattered seromucous
digestive tube in general, is missing in the mouth and Pharyngeal musculature glands are present, mostly where there is pseudostrati-
pharynx. Its place is occupied by an elastic network fied columnar epithelium. The muscular layer, made up
in the pharynx. Mucous glands of skeletal muscle, is present as somewhat irregularly
arranged layers.
The lip has a framework of skeletal muscle, chiefly
the orbicularis oris muscle. External to this are typical
subcutaneous tissue and skin with hair follicles, seba- Section through soft palate
ceous glands, and eccrine sweat glands. On the inner (Hematoxylin-eosin, x7)

side of the muscular framework is the submucosa con- Pharyngeal surface
taining rounded groups of mixed, predominantly mucous
glands (labial glands). The submucosa is not definitely
delimited from the covering mucous membrane, which
is composed, as described above, of lamina propria and
nonkeratinized, stratified, squamous epithelium. The free
margin of the lip has its characteristic red (or vermil-
lion) color because the epithelial cells contain much
translucent eleidin, and the vascular papillae of the
tunica propria indent the epithelium more deeply here.
The blood in the capillaries thus shows through to a
greater extent.
The general structure of the cheek is very similar to
that of the lip, the muscular framework being formed
by the buccinator muscle. Here some glands are exter-
nal to the muscular framework. In most of the lip and
the cheek, the mucous membrane is quite closely bound
to the muscular framework, preventing large folds of
mucous membrane from being formed that might be
easily bitten. Near the continuity of the mucous mem- Oral surface

brane with the gums, the attachment is much looser to
allow for freedom of movement.
The soft palate has a fibromuscular framework, with
the fibrous constituents (the expansion of the tendons
of the tensor veli palatini muscles) being more promi- The wall of the pharynx is for the most part composed
nent near the hard palate. On each side of the frame- of a mucous membrane, muscular layer, and thin
work is a mucous membrane. That on the oral side has fibrous sheath outside of the muscle that attaches the
an elastic layer separating the lamina propria from a pharynx to adjacent structures. The epithelium in the
much thicker submucosa containing many glands. The nasopharynx (except for its lowest portion) is pseu-
epithelium is the typical nonkeratinized, stratified, squa- dostratified, ciliated, and columnar, whereas that of
mous variety, which rounds the free margin of the soft the rest of the pharynx is nonkeratinized, stratified,
palate and extends for a variable distance onto the pha- and squamous. The lamina propria is fibroelastic, with
ryngeal surface. scattered small papillae indenting the epithelium. The

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 85

Plate 2-17  Upper Digestive Tract: PART I

MEDIAN SECTION

Sphenoidal sinus Pharyngeal opening of pharyngotympanic
Nasopharynx (auditory, eustachian) tube

Soft palate Sella turcica

Palatine glands Pharyngeal tonsil

Nasal septum Frontal sinus Spheno-occipital synchondrosis
Palatine tonsil Pharyngeal tubercle
of occipital bone

Oropharynx Pharyngeal raphe
Hard palate Anterior longitudinal ligament
Anterior atlanto-occipital
Oral cavity membrane

Apical ligament of dens

Incisive Anterior arch of
canal atlas (C1 vertebra)

Pharynx Body of C1 Dens of
tongue C2 axis (C2
The pharynx is a musculomembranous tube; much of vertebra)
its anterior wall is absent due to the fact that the right Foramen C3 Pharyngeal
and left nasal cavities, oral cavity, and larynx open into cecum constrictor
its anterior side. It extends from the base of the skull to Lingual tonsil C4 muscles
the inferior border of the cricoid cartilage at the level C5 C1 Bucco-
of the lower margin of the sixth cervical vertebra, at Root of tongue pharyngeal
which time it becomes continuous with the esophagus. Genioglossus fascia
In addition to the cavities already listed, the pharynx muscle Retro-
also communicates with the middle ear on each side by Epiglottis pharyngeal
means of the auditory (eustachian) tube; this fact explains Geniohyoid space
how infections spread from the pharynx to the middle muscle Pre-
ear, making a total of seven cavities with which it has Mandible vertebral
communication. The transverse diameter of the pharynx Mylohyoid fascia and
exceeds the anteroposterior diameter, which is greatest muscle anterior
superiorly and is diminished to nothing inferiorly Hyoid bone longitudinal
where the anterior and posterior walls are in contact Hyo-epiglottic ligament ligament
unless separated during the act of swallowing. The Thyrohyoid membrane
transverse diameter does not differ greatly throughout
the length of the pharynx, except where it narrows Laryngopharynx C6
at the lower end. Laryngeal inlet (aditus)

The posterior wall of the pharynx is attached superi- Thyroid cartilage
orly to the pharyngeal tubercle on the inferior surface of
the basilar part of the occipital bone, its adjacent area, Vocal fold C7
and the undersurface of the petrous portion of the tem- Transverse arytenoid muscle
poral bone medial to the external aperture of the carotid
canal. The lateral wall has several attachments. It is Cricoid cartilage T1
attached superiorly to the cartilaginous portion of Trachea
the auditory tube, which pierces the wall in this area.
Anteriorly it connects to the lower, posterior border of Esophagus
the medial pterygoid plate and its hamulus, as well as Esophageal muscles
the pterygomandibular raphe, the inner surface of the
mandible (near the posterior end of the mylohyoid Thyroid gland
line), the side of the root of the tongue, the hyoid bone, Superficial (investing) layer
and finally the thyroid and cricoid cartilages. Inferiorly, of deep cervical fascia
the walls of the pharynx continue as the walls of the
esophagus. Pretracheal fascia

The pharyngeal lining is a mucous membrane that is Suprasternal space (of Burns)
continuous with the lining of the cavities communicat- Manubrium of sternum
ing with the pharynx. External to the mucous mem-
brane of the posterior and lateral walls is a sheet of The posterior pharyngeal wall is separated from the On the basis of openings in its anterior wall, the
fibrous tissue, more defined superiorly than inferiorly, prevertebral fascia overlying the anterior arch of atlas pharynx is divided into the nasopharynx, oropharynx, and
known as the pharyngeal aponeurosis (pharyngobasilar and the bodies of the second to the sixth cervical ver- laryngopharynx. The nasopharynx typically has a purely
fascia), and external to this is the muscular layer of the tebrae (partially covered by the longus colli and longus respiratory function (acting as a passageway for air and
pharynx. On the outer surface of the muscular layer is capitis muscles) by a minimal amount of loose fibrous not for food) and remains patent because of the bony
another fascial covering, the buccopharyngeal fascia. connective tissue. This allows the pharynx some degree framework to which its walls are related. The anterior
of freedom of movement and forms a retropharyngeal wall is entirely occupied by the choanae (posterior
space. Under anesthesia it is possible to palpate these nares), with the posterior border of the nasal septum
bony structures as far caudally as the fourth or fifth between them. The posterior wall and roof form a con-
cervical vertebra. tinuous arched wall, with the roof extending from the

86 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 2-18  Mouth and Pharynx

OPENED POSTERIOR VIEW

Base of skull (basilar part of occipital bone)

Pharyngeal tonsil

Nasal septum

Choanae Torus tubarius
Pharyngeal opening of
pharyngotympanic (auditory,
eustachian) tube

Styloid process

Pharynx (Continued) Nasopharynx Pharyngeal
Oropharynx recess
superior margin of the choanae (where it is continuous Laryngo- Torus levatorius
with the roof of the nasal cavities) to about the midpoint pharynx (fold caused by
of the basilar portion of the occipital bone; the posterior Esophagus levator veli
wall extends from this point caudally to about the lower palatini muscle)
border of the anterior arch of the atlas. In the region fauces. Inferior to the isthmus, the anterior wall is Parotid gland
where the roof and posterior wall meet, the mucous formed by the posterior third of the tongue. Between Inferior nasal
membrane is thrown into many variable folds, with an the tongue and epiglottis are the valleculae, spaces concha
accumulation of nodular and diffuse lymphoid tissue where foreign bodies may lodge. Salpingopharyngeal
(extensively developed in children, atrophied in adults) fold
forming the pharyngeal tonsil (adenoids). In the midline, The laryngopharynx lies posterior to the larynx and Angle of mandible
near the anterior margin of the pharyngeal tonsil, is a anterior to the fifth and sixth cervical vertebrae. The Submandibular gland
minute flask-shaped depression of mucous membrane, superior part of the anterior wall contains the roughly Soft palate
known as the pharyngeal bursa. Also in the midline, triangular laryngeal inlet (aditus), the borders of which Palatine tonsil
near the anterior limit of the roof, and submerged in are formed by the margins of the epiglottis, the aryepi- Uvula
the mucosa or lying in the periosteum, a microscopic glottic folds, and the interarytenoid incisure. Inferior to the Prominence caused by
remnant of the Rathke pouch (pharyngeal hypophysis) greater horn of hyoid bone
can be found, which is grossly visible only when it has Palatopharyngeal arch
become cystic or has formed a tumor. Root of tongue
Epiglottis
The incomplete floor of the nasopharynx is formed Prominence caused by superior
by the posterosuperior surface of the soft palate with an horn of thyroid cartilage
opening from the nasal to the oral pharynx between the Laryngeal inlet (aditus)
soft palate and the posterior wall of the pharynx. This Aryepiglottic fold
opening is closed by bringing these two structures in Piriform fossa (recess)
contact. Fold over internal branch
of superior laryngeal nerve
On the lateral wall of the nasopharynx at the level of Cuneiform tubercle
the inferior concha is the pharyngeal opening of the audi- Corniculate tubercle
tory tube, with the pharyngeal recess (fossa of Rosen­ Interarytenoid notch
müller) posterior to it. The levator cushion (produced Prominence over lamina
by the levator veli palatini muscle) bulges into the infe- of cricoid cartilage
rior margin of the triangular opening, and coursing Trachea
inferiorly from the posterior lip is the salpingopharyngeal
fold produced by the muscle of the same name. In child- laryngeal opening, the laryngopharynx only transmits
hood, a considerable mass of lymphoid tissue (tubal food and is purely alimentary in function. The mucous
tonsil) may be present around the opening of the audi- membrane of the anterior wall overlies the posterior
tory tube and may enlarge, blocking drainage from the surfaces of the arytenoid cartilages and the lamina
middle ear. of the cricoid cartilage (mostly covered by laryngeal
muscles). Inferior to the laryngoepiglottic fold on each
The oropharynx extends from the inferior border of side is the piriform recess, located between the cricoid
the nasopharynx to the level of the pharyngoepiglottic and arytenoid cartilages medially and the lamina of the
folds, with the epiglottis protruding into it. This part of thyroid cartilage laterally. This is another location
the pharynx carries both air and food. The posterior where foreign bodies may lodge.
wall remains in relation to the bodies of the second to
fourth cervical vertebrae, whereas the anterior wall is
deficient superiorly where the oropharynx and oral
cavity communicate by means of the isthmus of the

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 87

Plate 2-19  Upper Digestive Tract: PART I

Temporal bone
Sphenoidal bone
Temporal fossa
Zygomatic arch
Condylar process of mandible

Mandibular notch

Coronoid process of mandible

Bony Framework of Mouth Lateral pterygoid plate (broken line) Mastoid
and Pharynx Hamulus of medial process
pterygoid plate (broken line) External
The bony framework of the mouth is composed largely Pterygomandibular acoustic meatus
of the two maxillae, immovably attached to other bones raphe (broken line) Atlas (C1)
of the skull, and the mobile mandible. The portions of Ramus Styloid process
the maxillae contributing to the formation of the bony Mandible Angle Axis (C2)
palate have been previously described, and the alveolar Body Stylomandibular
processes of the maxilla have been referred to as pro- ligament
viding the sockets for the upper teeth. Other bony Stylohyoid ligament C3 vertebra
structures contributing to the framework of the mouth Body C7 vertebra
and pharynx, serving as attachments for muscles of
the mouth and pharynx, are parts of the palatine, sphe- Hyoid bone Lesser horn T1 vertebra
noid, temporal, occipital, and hyoid bones as well as the Greater horn
zygomatic arch. 1st rib
Epiglottis
The palatine bone is interposed between the maxilla
and the pterygoid process of the sphenoid bone, and Thyroid cartilage
its horizontal portion forms the framework of the pos- Cricoid cartilage
terior part of the hard palate. Its pyramidal process Trachea
articulates with the lower portions of the medial and
lateral pterygoid laminae and helps to complete the Infratemporal fossa Foramen ovale
pterygoid fossa. Foramen spinosum
Tuberosity of maxilla Spine of sphenoidal bone
The sphenoid bone is located in the base of the skull Pyramidal process
posterior to the ethmoid, frontal, palatine, and maxil- of palatine bone Sphenopalatine foramen
lary bones. It is anterior to the occipital and temporal Alveolar process of maxilla Pterygopalatine fossa
bones, and it has the right and left pterygoid processes
extending inferiorly from its body. Each pterygoid Choanae (posterior nares)
process has a medial and lateral pterygoid plate, with a
pterygoid hamulus projecting posterolaterally from the Lateral plate of pterygoid
medial pterygoid plate, to which the pterygomandibular Medial plate process
raphe attaches and around which the tendon of the Hamulus
tensor veli palatini muscle passes. The greater wing of
the sphenoid forms the anterior parts of the temporal The basilar portion of the occipital bone is posterior of the mouth (and related tongue) and is important in
and infratemporal fossae. The spine of the sphenoid, to to the body of the sphenoid bone and forms the bony the movements of these structures through the muscles
which the sphenomandibular ligament attaches, is just framework of the roof and the superior part of the that attach to it. The hyoid bone is also important as
medial to the mandibular fossa of the temporal bone. posterior wall of the pharynx. The pharyngeal tubercle the origin of the middle pharyngeal constrictor muscle.
on the inferior surface of the basilar portion of the
The external acoustic meatus is an obvious landmark in occipital bone, anterior to the foramen magnum, is the Supplementing the bony framework in supplying
the temporal bone that extends toward the middle ear. superior attachment of the median raphe of the pharynx. attachments to the muscles of the pharynx are the
Posterior to the meatus is the mastoid process, on the thyroid and cricoid cartilages that give origin to the
medial side of which is the mastoid notch, where the The hyoid bone has a body, as well as a greater and inferior pharyngeal constrictor and some insertion to
posterior belly of the digastric muscle attaches. Antero- lesser horn on each side. It is a key structure in the floor the stylopharyngeus muscle.
inferior to the meatus is the mandibular fossa for the
articulation with the condyle of the mandible. Inferior
to the meatus and posterior to the mandibular fossa is
the styloid process, which projects for a variable distance
inferiorly and slightly anteriorly. The squamous portion
of the temporal bone is the extensive flat portion of the
bone superior to the meatus that, together with parts
of the greater wing of the sphenoid, frontal, and parietal
bones, forms the temporal fossa for the attachment of
the temporalis muscle. The petrous portion of the tem-
poral bone extends medially and somewhat anteriorly
from the meatus to insinuate itself between the basilar
portion of the occipital bone and the infratemporal
portion of the greater wing of the sphenoid.

The zygomatic arch forms a buttress over the infra-
temporal fossa and gives origin to the masseter muscle.
It is made up (from front to back) by the zygomatic
process of the maxilla, the zygomatic bone, and the
zygomatic process of the temporal bone.

88 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 2-20  Mouth and Pharynx

SAGITTAL SECTION
Medial pterygoid plate
Cartilaginous part of auditory
(pharyngotympanic, eustachian) tube
Tensor veli palatini muscle
Pharyngobasilar fascia
Levator veli palatini muscle

Palatine aponeurosis and tendon
of tensor veli palatini muscle

Musculature of Pharynx Pharyngeal tubercle (basilar part
of occipital bone)
Much of the framework of the lateral and posterior
walls of the pharynx is formed by an outer and inner Pharyngeal raphe
layer of musculature. These layers are not completely
separable throughout, because in some places they are Anterior longitudinal ligament
definitely intermingled and overlap. The outer layer
is more nearly arranged in a circular fashion and is C1 Anterior atlantooccipital
made up of the three constrictor muscles of the C2 membrane
pharynx, designated as superior, middle, and inferior
pharyngeal constrictors, which overlap each other. The Apical ligament of dens
inner layer, which falls far short of being a complete Salpingopharyngeus
layer, is longitudinally arranged and is composed of the muscle
stylopharyngeus, palatopharyngeus, and salpingopha- Muscles of soft palate
ryngeus muscles plus some other variable and irregular
bundles of muscle fibers. Palatopharyngeal sphincter
(Passavant’s ridge)
The superior pharyngeal constrictor muscle is quadrilat- Pterygoid hamulus
eral in shape and somewhat thin. It originates from the Superior pharyngeal
posteroinferior edge of the medial pterygoid plate, the constrictor muscle
hamulus of the medial pterygoid plate, the pterygoman- Pterygomandibular raphe
dibular raphe (which runs from the hamulus to the
lingula of the mandible), the posterior one fifth or so Palatopharyngeus muscle
of the mylohyoid line and the adjacent part of the alveo-
lar process of the mandible, and the side of the root of Hyoglossus C3 Buccinator muscle
the tongue (the glossopharyngeus muscle). From this muscle Glossopharyngeal part of
extensive line of origin, the fibers course posteriorly, Geniohyoid C4 superior pharyngeal
with the lower fibers passing somewhat inferiorly and muscle constrictor
medially to meet the ones from the opposite side in the Mylohyoid C5 Stylopharyngeus muscle
median pharyngeal raphe. This raphe extends most of muscle C6 Stylohyoid ligament
the length of the posterior wall of the pharynx, being Hyoid bone Styloglossus muscle
attached superiorly to the basilar part of the occipital bone Middle pharyngeal
at the pharyngeal tubercle, to which the uppermost fibers Thyrohyoid constrictor muscle
of the superior constrictor are also attached. The curved membrane Fibers to pharyngoepiglottic
upper edge of the muscle passes deep to the auditory Thyroid cartilage fold
tube and is thus separated by a short distance from the Median Buccopharyngeal fascia
base of the skull except at the midline posteriorly. At cricothyroid ligament and retropharyngeal space
this gap the only framework of the pharynx is the pha- Prevertebral fascia and
ryngobasilar fascia. The buccinator muscle runs anteriorly Corniculate and anterior longitudinal
from the pterygomandibular raphe, which serves as part arytenoid cartilages ligament
of its origin, and this muscle and the superior constric-
tor thus form a continuous sheet, which is therefore the Cricoid cartilage Internal branch of superior
continuous framework of the lateral wall of the oral and Trachea laryngeal nerve
oropharyngeal cavities. A slip of the superior part of the Longitudinal pharyngeal
superior constrictor muscle blends into the palatine muscles
aponeurosis, forming the so-called palatopharyngeal
sphincter, contraction of which produces a ridge (Pas- Inferior pharyngeal
savant ridge) against which the soft palate is raised. A constrictor muscle
triangular gap filled with fibrous connective tissue can
be noted between the lower border of the superior Pharyngeal aponeurosis
pharyngeal constrictor muscle, the posterior border of
the hyoglossus muscle, and the upper border of the middle Cricopharyngeus
pharyngeal constrictor muscle. The stylopharyngeus muscle (part of inferior
muscle inserts into this gap between the superior and pharyngeal constrictor)
middle constrictors. The stylohyoid ligament and glos-
sopharyngeal nerve also cross this gap. C7 Cricoid attachment
of longitudinal
The middle pharyngeal constrictor muscle has a V-shaped esophageal muscle
line of origin, with the V resting on its side and the
angle pointing anteriorly. The superior arm of this V is Circular esophageal muscle
formed by the terminal portion of the stylohyoid liga-
ment and the lesser horn of the hyoid bone, whereas Longitudinal esophageal muscle

the inferior arm of the V is formed by the entire length are overlapped by the inferior constrictor and reach
of the greater horn of the hyoid bone. From this rather quite far inferiorly in the posterior wall of the pharynx,
narrow origin the fibers fan out widely, with the upper to about the level of the superior border of the cricoid
fibers coursing superiorly while curving posteriorly cartilage. The middle constrictor’s fibers fuse and blend
and medially. The middle fibers course horizontally with those of the other side in the median raphe.
and curve posteriorly and medially. The inferior fibers Between the lower border of the middle constrictor and
course inferiorly and curve posteriorly and medially. the upper border of the inferior constrictor, a triangular
The medial pharyngeal constrictor’s superior fibers gap is noted, which is bounded anteriorly by the thyro-
overlap the superior constrictor, and the inferior fibers hyoid muscle.

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 89

Plate 2-21  Upper Digestive Tract: PART I

LATERAL VIEW
Tensor veli palatini muscle Levator veli palatini muscle

Lateral pterygoid plate Pharyngobasilar fascia

Pterygoid hamulus

Buccinator muscle (cut)
Pterygomandibular raphe

Buccinator crest Styloid process Digastric
of mandible muscle
(posterior
Oblique line belly) (cut)
of mandible
Superior pharyngeal constrictor
muscle
Styloglossus muscle

Musculature of Pharynx Stylohyoid ligament

(Continued) Stylopharyngeus muscle

The inferior pharyngeal constrictor muscle is relatively Digastric muscle (anterior belly) Middle pharyngeal constrictor
thick and strong. It arises from the oblique line of the Mylohyoid muscle muscle
thyroid cartilage and the area just dorsal to that line, Hyoid bone Hyoglossus muscle
from a tendinous arch extending from the inferior end Greater horn of hyoid bone
of the oblique line of the thyroid cartilage to the lateral Stylohyoid muscle (cut)
surface of the cricoid cartilage. That portion arising Thyroid cartilage Superior horn of thyroid cartilage
from the cricoid cartilage is frequently referred to as
the cricopharyngeus muscle. As do the other constrictor Median cricothyroid ligament Thyrohyoid membrane
muscles, the inferior constrictor passes posteriorly and Cricothyroid muscle Inferior pharyngeal constrictor
then medially to blend with its counterpart at the pha- Cricoid cartilage muscle
ryngeal raphe. The cranial fibers pass more and more Trachea Zone of sparse muscle fibers
obliquely as they approach the raphe and overlap the
middle constrictor, reaching nearly as far superiorly as to the inferior constrictor muscle to travel superiorly Tendinous arch
the middle constrictor does. The fibers of the cricopha- behind the cricothyroid joint in entering the larynx.
ryngeus portion of the muscle course horizontally and Cricopharyngeus muscle
form an annular bundle with no median raphe. It does As their names indicate, the major action of the (part of inferior pharyngeal
blend to some extent with the related circular fibers of superior, middle, and inferior pharyngeal constrictor constrictor)
the esophagus, being referred to by some as the supe- muscles of the pharynx is to constrict the pharynx. They
rior esophageal sphincter. A zone of sparse musculature contract in sequence, grasping the bolus of food as it Esophagus
is present between the cricopharyngeus muscle and the passes from the mouth to the esophagus. The nerve Tracheoesophageal groove
rest of the inferior constrictor muscle, which creates a supply of the constrictor muscles of the pharynx is
weaker area in the posterior wall of the pharynx, where derived from the pharyngeal plexus. nates from the medial aspect of the base of the styloid
an instrument may accidentally pierce the wall. Just process and then passes inferiorly and anteriorly, going
below the inferior border of the cricopharyngeus The stylopharyngeus muscle is long, slender, and cylin- between the external and internal carotid arteries and
muscle, a triangular area (sometimes called the Laimer drical superiorly but flattens near its insertion. It origi- then entering the wall of the pharynx in the interval
triangle) occurs in which the posterior wall of the between the superior and middle constrictor muscles.
esophagus is variably deficient, because the longitudinal As it spreads out internal to the middle constrictor
muscle fibers of the esophagus tend to diverge laterally muscle, the greater horn of the hyoid bone, and the
and pass around the esophagus to attach on the cricoid thyrohyoid membrane, some of its fibers join the pala-
cartilage. It is thus seen that there is more than one topharyngeus muscle and insert on the superior and
weakened area in the posterior wall of the general posterior borders of the thyroid cartilage. Some fibers
region of the pharyngoesophageal junction, where pass into the pharyngoepiglottic fold, and they are
diverticula may occur. The recurrent laryngeal nerve
and accompanying inferior laryngeal vessels pass deep

90 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS

Plate 2-22  Mouth and Pharynx

PARTIALLY OPENED POSTERIOR VIEW Cartilaginous part
Basilar part of occipital bone Pharyngeal tubercle of pharyngotympanic
(auditory, eustachian)
Pharyngeal raphe Pharyngeal tonsil tube

Pharyngobasilar fascia

Choana

Musculature of Pharynx Digastric Pharyngo-
muscle basilar
(Continued) (posterior fascia
belly) Levator veli
primarily responsible for the production of this fold. Styloid palatini
The remaining fibers of the stylopharyngeus muscle process muscle
spread between the constrictor muscles and the mucous Stylohyoid Superior
membrane (blending to some extent with the constric- muscle pharyngeal
tors) and pass caudally in the posterolateral wall of the Stylopharyngeus constrictor
pharynx, until they fade out and attach to the fibrous muscle muscle
aponeurosis of the pharynx a short distance above the Medial Salpingopha-
cricopharyngeus muscle. The stylopharyngeus muscle pterygoid muscle ryngeus muscle
receives its nerve supply from the glossopharyngeal Accessory muscle Uvula
nerve, which curves around the posterior border of the bundle from Palatopha-
muscle onto the lateral aspect in its course toward its petrous part of ryngeus muscle
final distribution on the posterior third of the tongue. temporal bone Middle pharyngeal
(petropharyngeus constrictor muscle
The salpingopharyngeus muscle consists of a slender muscle) Root of tongue
bundle that produces the mucous membrane fold of the Superior pharyngeal Stylopharyngeus
same name, which is rather variable in its degree of constrictor muscle muscle
distinctness. This muscle arises from the inferior part Hyoid bone Pharyngo-epiglottic
of the cartilaginous part of the auditory tube, near its (tip of greater horn) fold
orifice, and passes into the wall of the pharynx, blending Middle pharyngeal Aryepiglottic fold
in part with the posteromedial border of the palatopha- constrictor muscle
ryngeus muscle. Some authors have described this Epiglottis Inferior
muscle as a part of the levator veli palatini muscle, which Inferior pharyngeal pharyngeal
gives a definite clue as to its action. The salpingopha- constrictor muscle constrictor
ryngeus muscle receives its nerve supply from the pha- Cuneiform tubercle muscle
ryngeal plexus. Corniculate tubercle (cut edge)
(Transverse and oblique) Longitudinal
The palatopharyngeus muscle, together with the arytenoid muscles pharyngeal muscles
mucous membrane covering it, forms the palatopharyn- Posterior cricoarytenoid muscle Superior horn of
geal fold, also known as the posterior pillar of the thyroid cartilage
fauces. This muscle takes its inferior origin from a Cricopharyngeus muscle (part of Thyrohyoid membrane
narrow fasciculus on the dorsal border of the thyroid inferior pharyngeal constrictor) Pharyngeal aponeurosis
cartilage near the base of the superior horn and by a Cricopharyngeus muscle (part of
broad expansion from the pharyngeal aponeurosis in the Longitudinal esophageal muscle inferior pharyngeal constrictor)
area posterior to the larynx, just cranial to the cricopha- Internal branch of
ryngeus muscle. As the fibers pass cranially, they form a rather compact muscular band that inserts into the superior laryngeal nerve
aponeurosis of the soft palate by two lamellae, separated Posterior border of thyroid cartilage
by the insertion of the levator veli palatini and the lamina
uvula. As indicated above, some of the fibers of the
palatopharyngeus muscle intermingle with the stylo- Cricoid attachment of longitudinal
pharyngeus muscle. The actions of the palatopharyn- esophageal muscle
geus muscle include constriction of the pharyngeal Circular esophageal muscle
isthmus by approximation of the palatopharyngeal
folds, depression of the soft palate, and elevation of the pharynx and larynx. This muscle also receives its nerve
supply from the pharyngeal plexus.

Additional muscle bundles are quite common, such
as the one labeled accessory muscle bundle from petrous part
of temporal bone (petropharyngeus muscle). Other addi-
tional muscles are brought about by the splitting of one
of the usual muscles, quite commonly the stylopharyn-
geus. The majority of the additional muscles tend to
run longitudinally.

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 91

Plate 2-23  Upper Digestive Tract: PART I

ARTERIES OF ORAL AND PHARYNGEAL REGIONS

From ophthalmic Maxillary artery
artery Middle meningeal artery Deep auricular and anterior tympanic arteries
Deep temporal arteries
Supra- Supra- Transverse facial artery (cut)
trochlear orbital

artery artery

Blood Supply of Mouth Masseteric artery
and Pharynx Dorsal nasal artery

Infra-orbital artery
Angular artery

The external carotid artery and its branches are respon- Sphenopalatine Occipital
sible for essentially the total arterial supply of the artery artery
mouth and pharynx. The common carotid artery, Descending Auriculo-
arising from the brachiocephalic trunk on the right and palatine artery temporal
the arch of the aorta on the left, bifurcates at the level Posterior superior nerve
of the superior border of the thyroid cartilage into alveolar artery Superficial
external and internal carotid arteries. From here the Buccal artery temporal artery
external carotid artery courses superiorly to a point Superior Posterior auricular artery
posterior to the neck of the mandible, dividing in the labial artery Ascending pharyngeal artery
substance of the parotid gland into the maxillary and Occipital artery and
superficial temporal arteries. The parotid gland surrounds Inferior sternocleidomastoid branch
part of the external carotid artery and the beginnings labial artery Glossopharyngeal nerve (IX)
of its terminal branches. The gland gets many small Buccinator Ascending palatine artery
branches from these vessels in its substance. muscle and Tonsillar artery
parotid duct Facial artery
Five of the branches of the external carotid artery are (cut) Lingual artery
involved in the supply of the mouth and pharynx. The Ascending pharyngeal
superior thyroid artery leaves the anterior aspect of the Mental branch of artery
external carotid near its beginning and courses inferi- inferior alveolar artery Internal carotid artery
orly and anteriorly on the external surface of the infe- Facial artery Vagus nerve (X)
rior pharyngeal constrictor muscle, passing deep to the Submental artery Superior cervical
sternohyoid and omohyoid muscles to ramify on the Superior pharyngeal cardiac nerve
anterolateral surface of the thyroid gland. Near its constrictor muscle Sympathetic trunk
origin, the superior laryngeal artery pierces the thyrohy- Inferior alveolar artery Anterior scalene muscle
oid membrane to supply the tissues of the larynx. The and lingual branch Phrenic nerve
lingual artery arises from the anterior surface of the Submandibular gland Ascending cervical
external carotid, a short distance superior to the supe- Mylohyoid branch of artery
rior thyroid artery, opposite the tip of the greater horn inferior alveolar artery Middle scalene
of the hyoid bone. It courses anteriorly and slightly Hypoglossal nerve (XII) muscle
superiorly deep to the stylohyoid muscle, the posterior Suprahyoid artery Inferior thyroid
belly of the digastric muscle, and the hypoglossal nerve, External carotid artery artery
and then passes medial to the hyoglossus muscle along Superior laryngeal artery Thyrocervical trunk
the superior border of the greater horn of the hyoid. Superior thyroid artery Subclavian artery
The facial artery, coming from the anterior aspect of the Cricothyroid artery
external carotid slightly superior to the lingual, is tortu- Common carotid artery anastomoses with the inferior labial artery, and the
ous throughout its length to allow for movements of labial branch of the infraorbital artery anastomoses with
the head and of the lower jaw. It courses anteriorly and The lips, which are very vascular, are supplied chiefly the superior labial artery.
superiorly deep to the digastric and stylohyoid muscles by the superior and inferior labial branches of the facial
sheltered by the mandible, lies in a groove on the sub- artery, each of which courses from near the angle of the The cheek receives much of its arterial supply by way
mandibular gland, and then curves superiorly around mouth, where they arise, toward the midline of each of the buccal artery, which springs from the second part
the inferior border of the mandible near the anterior respective lip to meet the one on the opposite side. For of the maxillary artery and runs anteroinferiorly on the
margin of the masseter muscle. From here it runs ante- the most part, they lie between the orbicularis oris external surface of the buccinator muscle.
riorly and superiorly across the cheek and along the side muscle and the mucous membrane related to its inner
of the nose, to end as the angular artery at the medial surface. The mental branch of the inferior alveolar artery, The arterial supply of the superior arcade of teeth,
angle of the eye. The maxillary artery, the larger of the a branch of the first part of the maxillary artery, their alveolar processes, and gums is furnished in the
two terminal branches of the external carotid, passes
anteriorly between the ramus of the mandible and the
sphenomandibular ligament (first part), and continues
anteriorly either deep or superficial to the lateral ptery-
goid muscle (second part), between the two heads of
which it dips to reach the pterygopalatine fossa (third
part). The infraorbital artery, which is a continuation of
the maxillary, courses through the infraorbital canal of
the maxilla to end in terminal branches on the face as
it leaves the infraorbital foramen. The ascending pharyn-
geal artery arises from the posteromedial aspect of the
external carotid very near its beginning. From here it
ascends vertically between the internal carotid artery
and the posterolateral aspect of the pharynx, to go as
high as the undersurface of the base of the skull.

92 THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS