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nato my and hysi I y

Eldridge E Johnson, PhD

Anatomy and physiology are fundamental, and they stratum spinosum, stratum granulosum, stratum lu-
correlate with pharmacy by establishing the normal cidum, and stratum corneum.
standard for structure and function of the healthy The dermis consists of dense, irregular connective
individual. This factual standard provides the basis tissue that is highly vascular and rich in lymphatics
for identifying the presence and degree of disease and and cutaneous nerves.
pathology. It also provides a means of understand- The hypodermis is a looser connective tissue layer
ing the process of medicinal application, movement, that facilitates movement of the overlying skin.
absorption, and target organ and tissue action. For clinical purposes, the skin is highly absorp-
Selected salient systems and focal topics reviewed tive and facilitates the uptake of topically applied
in this chapter are the integument system; muscu- medications, such as salves and ointments. Also,
lar system; skeletal system; cardiovascular system; subcutaneous medications may be administered to
lymphatic system; respiratory system; digestive vascular-rich deep connective tissue through hypo-
system; central nervous system; endocrine system; dermic injections.
urinary system; reproductive system; body fluids
and electrolytes; and cell structure, organization,
and physiology. 1.. 2. Muscular System
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The function of the mustular system is to dynamically


overcome gravity and to facilitate locomotion through
1..1 The Integument System
B
movement of the skeleton and various organs of
the body.
The integument system consists of the skin and asso-
ciated specializations such as nails, hair, and sebaceous
and sweat glands. Types of Muscle Cells
Skin is the largest nonvisceral organ of the body Skeletal muscle cells are voluntary and highly involved
and consists of the outer epithelial layer, called the epi- in movement of the skeleton and the musculoskeletal
dermis, and an inner connective tissue, known as the system. Skeletal muscle cells are multinucleated rec-
dermis. Skin serves to cool and rid the body of toxic tangular or cigar-shaped structures and are con-
waste through the secretion, excretion, and evapora- tained by a cell membrane called the plasmalemma
tion of sweat from sweat glands. It also protects the or sarcolemma.
body from desiccation and mechanical abrasion. Cardiac muscle cells are striated and involuntary
The epidermis is a nonvascular layer and is made and are found in the heart. They are responsible for
up of stratified squamous epithelium, which grows contraction of the heart. Smooth muscle cells are uni-
from the deeper basal layer to the outermost kera- nucleated and involuntary. Smooth muscle is located
tinized squamous cells of the corneum. Epidermis lay- in the walls of hollow organs, such as the stomach,
ers, from deep to superficial, are the stratum basale, intestines, bladder, blood vessels, and uterus.
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Organelles of the Skeletal Muscle Cell Classifications ami Types


The cytoplasm of the muscle cell is filled with syn- Skeletal muscles are classified according to size (mag-
chronously arranged and linearly organized protein num), shape (rhomboid), function (levator), and
strands called myofilaments. Mitochondria, Golgi, number of tendinous attachments (digastricus). Types
vesicles, lysosomes, and other organelles are ran- of skeletal muscle actions include flexion, extension,
domly situated between myofibrils. rotation, abduction, adduction, elevation, depression,
protraction, retraction, dilation, and constriction.
Myofilaments
Neuromuscular Junction
Each myofibril contains cross-striated regions of alter-
nating light and dark bands. The dark bands are called Skeletal muscle fibers require neuronal input to con-
A-bands. A-bands consist of overlapping thin actin tract or act. Efferent axons terminate on skeletal mus-
filaments and thick myosins. The light bands, or stri- cle cells at specialized synaptic sites of contact called
ations, are called I-bands. !-bands contain only thin motor end plates or the neuromuscular junction.
actin filaments. Z-lines are places where adjacent The motor end plate synapse is where the axon
thin filaments connect or abut to one another. terminal releases a neurotransmitter (usually acetyl-
Myofibrils can be subdivided into smaller linear choline) into the synaptic cleft. Specialized receptors
units called microfilaments. are located on the plasma membrane of the muscle
The Sliding Filament Theory of Muscle Contrac- cell that can be energized by the neurotransmitter to
tion suggests that thick and thin myofilaments inter- produce an axon potential in the muscle cell.
digitate and slide between and with one another
during muscle contraction. Calcium and adenosine
triphosphate (ATP) are vital in producing muscle
contraction.
The bony skeleton of the human is internally located
Endomysium and perimysium and provides protection from mechanical injury and
attachment for muscles. It stores and, when necessary,
A single skeletal muscle cell is enclosed or surrounded releases calcium and other vital inorganic salts; is
in a delicate layer of connective tissue layer called the instrumental in blood formation through bone mar-
endomysium. The endomysium of several closely row; and acts as scaffolding in overcoming gravity.
situated or adjacent muscle fibers blend together Bone cells types include the following:
to form coarser connective tissue called perimysium.
o Osteocytes. These mature melon-shaped bone cells
This tissue sequesters or organizes muscle fibers into
are trapped in lacunae and maintain bone matrix.
numerous muscle bundles. The perimysium is rich
Osteoclasts. These multinucleated bone cells en-
in blood vessels, which provide nourishment for the
zymatically digest and remodel bone matrix.
muscle.
Osteoblasts. These young bone cells actively
build bone matrix.
Epimysium
Mature bone matrix consists of layers of helically or-
The overall muscle organ is covered by a layer of ganized connective tissue fibers (collagen, elastin, and
coarse connective tissue, which is called the epimy- reticulin) that surround blood vessels in Haversian
sium. The epimysium coalesces at each end of the systems. The bone matrix is also infiltrated by calcium
muscle at its bony tendinous attachment. and phosphate crystalline salts, which are responsible
for its rigidity and represent 65% of a bone's weight.
Origins, insertions, and action
Muscles attach to bones through tendons. The tendi-
Haversian Systems
nous muscle attachment that moves the least during The crystallized and calcified lamellae of the Haversian
muscle contraction is called the origin; the attach- system contain small, shallow depressions called lacu-
ment that moves the most is the insertion. The work nae. These lacunae contain osteocytes. Each lacuna is
that the muscle performs during its contraction is connected to several fracture-line-like linear spaces in
called the action; adjacent matrix called canaliculi. Canaliculi are filled
Anatomy and Physiology

by cytoplasmic processes of the osteocyte and pro- The nucleus pulposus may be herniated and pro-
vide an avenue whereby nutrients can travel in the ject through the annulus fibrosus posterior laterally
calcified bone matrix. and compress the spinal nerve, resulting in sciatica
Flat bones consist of two tables of adult bone sep- and lower back pain.
arated by an inner layer of red bone marrow called
diploie. Long bones contain an outer shell of mature
lamellae bone and an inner and central core of bone
Vertebrae specializations and classification
marrow. The inner layer of bone marrow is sepa- The cervical vertebrae are the smallest vertebrae.
rated from the innermost lamellae of bone by a deli- They facilitate spinal movement (rotation, flexion,
cate connective layer called the endosteum. and extension).
Bones are usually covered on the surface by a The atlas, which is the first cervical vertebra,
highly vascular, dense connective envelope called the contains no centrum or body and articulates with
periosteum. The periosteum also contains reserve or the condyles of the occipital bone of the skull. This
primitive bone cells that are capable of producing arrangement provides extension and flexion of the
new bone cells and matrix. This layer is important in skull on the atlas.
the healing and repair of bone fractures. The axis, which is the second cervical vertebra,
contains a cranially oriented projection from its
Classification of Bone centrum or body called the dens. The dens articulates
with the anterior arch of the atlas, thus facilitating
Bones can be classified as short, long, irregular, and rotary movement.
flat. They are attached to one another by joints. Strong, Regional differences exist in the morphology of
dense regular connective tissue bands called ligaments cervical through coccygeal vertebrae. Each of the
generally hold joints together. 12 thoracic vertebrae is attached whole or partially
Joints are movable or nonmovable. Selected mov- to a rib and provides protection to thoracic viscera
able joints include ball and socket, hinge, sliding, and and points of attachment for thoracic musculature.
peg in socket. The five independent lumbar vertebrae are larger and
Muscles attach to bone by tendons. are the strongest components of the vertebral column.
Red bone marrow contains sinusoidal-line blood The five sacral vertebrae are fused into a single, solid
vessels and primitive blood-forming cells that divide triangular mass of bone, which articulates with the
and differentiate into mature blood corpuscles. iliac bones of the pelvic girdle as the sacroiliac joint.
Coccygeal vertebrae are three to four in number and
Organization of the Skeleton are small and vestigial. ·
Curvatures of the vertebrae and spine ,include the
The skeleton proper can be subdivided into two units: cervical curvature, the thoracic curvature, the lum-
the axial and appendicular skeleton. The axial skeleton bar curvature, and the sacral curvature
consists of the skull and vertebral column. The appen-
dicular skeleton contains the upper and lower extrem-
ities and the pectoral and pelvic girdles. Ribs
Selected bones of the cranium include the frontal, Twelve pairs of ribs can be included with the axial
maxilla, mandible, sphenoid, parietal, temporal, skeleton, and they articulate with thoracic vertebrae
occipital, nasal, and zygoma. Selected vertebrae and posteriorly and the sternum anteriorly. The ribs and
their number on the vertebral column are as follows: clavicle attach to the sternum anteriorly, and the
cervical (7), thoracic (12), lumbar (5), sacral (5), and sternum acts to limit the thorax ventrally.
coccygeal (3). Rib types are as follows:
Vertebra components include the body, pedicles,
lamina, transverse process, and posterior spine. The rn True (1-7)
neural canal contains the spinal cord and is located False (8-10)
!:il
between the lamina and pedicles. HJ Floating (11-12)
Spaces between adjacent vertebrae are occupied
by a fibrocartilaginous body called the interverte-
Sternum
bral disc. The disc can be subdivided into an outer
region of biaxially arranged layers of fibrocartilage The sternum is located anteriorly in the thorax
called the annulus fibrosus and an inner soft, pulpy and consists of the manubrium, body, and xiphoid
center referred to as the nucleus pulposus. process.
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The Appendicular Skeleton Oxygen and carbon dioxide readily diffuse from
the blood cells and plasma across the thin, simple
The appendicular skeleton consists of the pectoral gir- squamous endothelial layer of the intima into the
dle and upper extremity and the pelvic girdles and connective tissue and the surrounding tissue fluid.
lower extremity. Bones of pectoral girdle are the clav-
icle and the scapula.
Major bones of the upper limb include the humerus The Heart
of the arm, the radius and ulna of the forearm, the The heart is a modified blood vessel that functions to
carpal bones of the wrist, the metacarpal bones of pump blood to various parts of the body. The heart
the hand, and the phalanges of the digits. contains three tissue layers in cross section:
Bones of the pelvic girdle include the ilium, the
pubis, and the ischium. Ii! Epicardium. An outer layer of mesothelium and
Bones of the lower limb proper include the femur connective tissue.
l:lll Myocardium. A middle layer of several laminae
of the thigh, the tibia and fibula of the leg, the tarsal
bones of the ankle, the metatarsal bones of the foot, of cardiac muscle.
and the phalanges of the digits. ra Endocardium. An inner layer of simple squamous
epithelium.

1..4. The Cardiovascular System Gross structure of the heart


The human heart consists of four primary chambers:
The cardiovascular system is an enclosed entity and the right and left atria and right and left ventricles.
includes the heart, arteries, veins, and capillaries. Each atrium has an antechamber called the auricle.
The great blood vessels of the heart include veins
that bring deoxygenated blood to the right atrium
The Tissue Organization of Blood Vessels and arteries that carry deoxygenated and oxygenated
The intima is the innermost epithelial layer of blood blood away from the heart. These veins include the
vessels. The flat, plate-like squamous cells of the superior vena cava, inferior vena cava, and coronary
intima facilitate the flow of blood and prevent clot- smus.
ting. Mechanical damage or the accumulation of cal- The heart is located in the pericardia! sac, in the
cium and fatty deposits in the intima may cause blood central region of the thorax called the middle medi-
clots, which may cause cerebral accidents (strokes) astinum. Components of the pericardia! sac include,
and coronary artery heart disease. the fibrous pericardium and the serous pericardium,
The media is the middle layer of blood vessels and with its visceral and parietal layers.
is the thickest layer in arteries. The adventitia is wider The right atrium receives deoxygenated blood from
or thicker in veins. The smooth muscle cell media of the head, neck, and upper extremities through the
superior vena cava and from the thorax, abdomen,
arteries tends to be arranged in several circular layers:
pelvis, and lower extremities through the inferior
1 in arterioles and up to 25 in some large muscular
vena cava. Components of the right atrium include
arteries. The media may contain several laminae of
the pectinate muscles, crista terminalis, and fossa
elasti~ fibers.
ovalis. The right atrium constricts to force blood to
The adventitia is an outer layer of predominately the right ventricle through the tricuspid valve.
connective tissue. The adventitia of veins may con- The right ventricle is composed of the chordae
tain one or more longitudinally arranged smooth tendineae, the papillary muscles, the trabeculae
muscle layers and may contain scant or rich laminae carneae, and the aortic vestibule. The right ventricle
of elastic fibers. constricts to force blood through the pulmonary semi-
Types of arteries include large arteries, medium lunar valve to the pulmonary trunk. The pulmonary
arteries, small arteries, and arterioles. Veins, which trunk divides into right and left pulmonary arteries,
accompany arteries, usually have larger diameters which direct blood to right and left lungs.
and thinner walls. Types of veins include large veins, The left atrium consists of the left auricle, the
medium veins, small veins, and venules. pectinate muscles, and the openings for the four
Capillaries are the smallest blood vessels and con- pulmonary veins. Oxygenated blood (from the lungs)
sist of an endothelial layer surrounded by connective is sent to the left atrium through the four pulmonary
tissue. vems.
The left ventricle consists of the chordae tendineae, Lymph is composed of leukocytes and plasma-
papillary muscles, the trabeculae carneae, and the like tissue fluid. Lymph vessels consist of intima,
aortic vestibule. Contraction of the left atrium pro- media, and adventitia, which are highly disorganized
pels oxygenated blood through the mitral or bicus- tissues when compared with lamellae of arteries
pid valve to the left ventricle. Contraction of the left and veins.
ventricle projects oxygenated blood through the aor- Lymphatic tissue and organs include the diffuse
tic valve into the aorta and its branches. The cardiac lymph tissue (i.e., Peyer's patches of the small intes-
musculature of the left ventricle is three times thicker tines); partially encapsulated tissue (i.e., tonsils);
than that of the right ventricle. and totally encapsulated organs (i.e., the lymph
Components of the cardiac conducting system in- nodes, which filter lymph fluid of microbes and can-
clude the sinoatrial node, the atrioventricular node, cerous cells).
the atrioventricular bundle, and the Purkinje fibers. The thymus gland is located in the anterior thorax
The synchronous contraction of right and left atria and produces T-lymphocytes.
before that of right and left ventricles is provided by the The spleen filters the blood, produces white blood
cardiac conduction system. The cardiac conduction cells, and stores blood for emergency perfusion result-
system consists of modified cardiac muscle fibers that ing from hemorrhages. It contains concave and convex
are specialized for conducting fast nerve-like impulses surfaces and is generally located deep in the 9, 10,
in cardiac tissue. These fibers facilitate the synchronous and 11 ribs. An enlarged spleen may indicate the pres-
contraction of atria before ventricles. ence of infection.

Electrical activity of the heart


An electrocardiograph tracing has three components
1.. ftt The Respiratory System
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or waves: a P wave, which occurs with atria depolar- The function of the respiratory system is to filter,
ization (contraction); a QRS wave complex, which humidify, and transmit air to the lungs, where it oxy-
represents depolarization of the ventricles (contrac- genates blood. The nasal cavity filters and conditions
tion); and a Twave, which represents electrical activ- the aspired air.
ity (repolarization) or relaxation of the ventricles. The pharynx, larynx, trachea, bronchi, and bron-
chioles transmit air to the lungs, where the respiratory
system oxygenates the blood through thin-walled pul-
1. . 5m The lymphatic System monary alveoli and alveolar sacs.
The trachea and bronchi contain a skeleton of
The lymph nodes and the spleen, thymus gland, C-shaped rings of hyaline cartilage, a mucosa of res-
and tonsils produce lymphocytes, which contain piratory epithelium (pseudostratified ciliated colum-
macrophage-like, phagocytic lymphatic cells. These nar epithelium and goblet cells), and a submucosa
cells engulf and destroy invasive microbial cells. The that contains numerous mucous glands.
thymus gland is the source of thymic lymphocytes The lungs are bilateral organs; each is located in
(T-lymphocytes), which, after maturity, are distrib- the pleural cavity of the thorax. The left lung is di-
uted to other lymphatic organs. The spleen is the vided into two lobes by the oblique fissure. The right
largest lymph organ of the body and also functions lung is divided into three lobes by the horizontal and
to store and destroy old red blood corpuscles. oblique fissures.
Lymph fluid ultimately is returned to the venous The pulmonary alveolus consists of a single layer
system through the thoracic duct and right lymph of simple squamous epithelium (pulmonary epithe-
duct. The excessive accumulation of lymphatic fluid lium), which is adjacent to a basement membrane
in an extremity is a type of edema. and abuts against another layer of simple squamous
Lymph flow involves small lymph vessels in the epithelium (endothelium) of a capillary. This layer is
extremities and other parts of the body that pick up referred to as the blood-air barrier.
tissue fluid from deep and superficial connective tis- Oxygen passes from a region of higher .concentra-
sue, where it is conducted to larger vessels. These ves- tion in the pulmonary alveolus through the blood-air
sels empty the lymph into the thoracic duct and right barrier to an area of less concentration in the blood
lymphatic duct, which are the largest lymph vessels of the capillary where hemoglobin is oxygenated.
of the body. The thoracic duct empties lymph into Carbon dioxide is more highly concentrated in the
the left brachiocephalic vein. blood and travels by diffusion through the blood-air
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barrier to the lumen of the pulmonary alveolus, where The liver is the largest visceral organ of the body
it is exhausted. and is important in detoxifying the blood of pathogens
The diaphragm is the major muscle of respiration and toxins. It is shaped roughly like a pyramid lying
and is located between the thorax and the abdomen. on one side with its base on the right and its apex sit-
Contraction of this muscle causes an increase in uated to the left. The liver receives blood from the por-
thoracic volume and inhalation of air, whereas relax- tal vein. The blood contains nutrients absorbed from
ation of the diaphragm forces carbon dioxide-laden the stomach and intestines.
air out of the lungs in exhalation. The liver is an important exocrine organ and se-
cretes bile. Bile is a fatty emulsifier; after it is secreted
from the liver, it is stored and concentrated in the gall
bladder. Right and left hepatic ducts unite to form
1"7. The Digestive System Proper the common hepatic duct. The common hepatic duct
from the liver joins the cystic duct of the gall bladder
The abdomen is the region between the thorax (above)
to form the common bile duct, which attaches to the
and the pelvic cavity (below). The diaphragm sepa-
descending portion of the duodenum.
rates the abdomen from the thorax. No true muscular
The hepatic porta contains the portal vein, the
or connective partition demarcates the true pelvis from
hepatic artery, and the common bile duct. The liver
the abdominal cavity.
gives off two excretory ducts, the right and left hepatic
Selected organs of the abdomen include the liver, the
ducts, from hepatic lobes of the same name.
pancreas, the kidney, the suprarenal glands (adrenal),
The liver possesses a dual blood supply through
the stomach, the gall bladder, the small intestines, and
the portal vein and the hepatic artery. The portal
the large intestines. The abdomen can be subdivided
vein is formed as a result of juncture of the superior
into four quadrants by the intersection of the vertically
mesenteric and splenic veins. The portal vein sup-
situated median plane and by a horizontally applied plies venous blood from the small and large intes-
plane through the umbilical region. tines to the liver as a component of the hepatic triad.
The parietal peritoneum consists of a layer of sim- The liver is also supplied with arterial blood through
ple squamous epithelium that lines the inner surface the proper hepatic branch of the celiac trunk.
of the anterior and posterior abdominal walls. The The gall bladder is located in the right vertical
visceral peritoneum is a similar epithelial layer that groove of the H-shaped hepatic portal or root of the
covers the outer surface of selected abdominal or- liver (on the visceral surface of the liver). It functions
gans. The space located between visceral and parietal to concentrate and store bile.
peritonea is called the peritoneal cavity. Several organs The cystic duct is the excretory duct of the gall
that are not entirely enclosed in peritoneum but are bladder, and it joins the common hepatic duct (which
located behind the peritoneum are referred to as retro- is formed from the union of the left and right hepatic
\
peritoneal structures. They include the duodenum, ducts) to form the common bile duct. The common
the pancreas, the kidneys, the ascending colon, and hepatic duct attaches and empties into the descending
the descending colon. or second part of the duodenum.
Intraperitoneal organs are enveloped by the vis- The pancreas is composed of a head, neck, body,
ceral peritoneum on several sides and attach to the and tail. The pancreas is located in the C-shaped con-
parietal peritoneum of the anterior or posterior ab- cavity of the duodenum, and the tail reaches the
dominal walls by peritoneal reflections. visceral surface of the spleen. It is centrally located and
Organs of the digestive system include the oral can be seen extending horizontally across the abdomen
cavity (teeth, tongue, and salivary glands); the esoph- in the transpyloric region at approximately Ll.
agus; the stomach; the small and large intestines; the The pancreas is both endocrine and exocrine in
rectum; and the anus. function, producing pancreatic enzymes as well as
Accessory glands of digestion include the salivary the hormone insulin. The islet pancreatic cells secrete
glands, the liver, the gall bladder, and the pancreas. insulin.
The salivary glands produce saliva, which contains The pancreas contains both main anq secondary
the enzyme amylase. They are anatomically associ- pancreatic ducts, which empty pancreatic enzymes into
ated with the oral cavity, where they project excre- the second part of the duodenum during digestion.
tory ducts to the mouth. Consequently, the process Pancreatic cancer can be diagnosed by compres-
of digestion begins in the mouth, where carbohy- sion of the bile duct and the resulting obstructive
drates are initially broken down by amylase. jaundice.
Hormones of the intestinal mucosa include secretin, The Small Intestine
gastrin, cholecystokinin, and enterocrinin.
The small intestine is roughly two meters and is com-
posed of the duodenum, the jejunum, and the ileum.
The Physiology of Digestion
Digestion is the process of breaking down large The duodenum
pieces of ingested food into simple molecules that The duodenum is the first part of the small intestine,
can be absorbed by the mucosa and lymphatic and and its name literally means 12 fingers. The C-shaped
blood vessels of the gastrointestinal (GI) tract (stom- arrangement of the duodenum encloses the head of
ach and small and large intestines). the pancreas. ,
Digestion begins in the oral cavity or mouth, The duodenum has four regional components:
where coarse and complex carbohydrates are bro- superior, descending, inferior, and ascending.
ken down into smaller particles and mixed with The second part of the duodenum receives both
saliva (containing salivary amylase), which trans- the common bile and main pancreatic ducts through
forms them into simpler carbohydrates. Mastication the hepatopancreatic ampulla. In contrast to the
breaks down large chunks of animal and plant food acidity of the stomach, the chemical environment of
materials (proteins, fats, and carbohydrates) into the duodenum is basic.
smaller units. Food is forced into the stomach by Tissue organization of the duodenum is as follows:
smooth and skeletal arranged muscle, which lines
the esophagus. iD The plica semicircularis contains numerous pro-
jected folds of mucosa and submucosa. These
structures increase the surface area of the intes-
The Stomach tinal mucosa.
The bolus of food is thoroughly mixed with gastric !i:J The mucosa consists of numerous finger projection-
juices (primarily hydrochloric acid) in the stomach like structures called intestinal villae.
The villi have a core of connective tissue covered
before it is released into the small intestine through
by a layer of simple columnar epithelium.
the gastroduodenal sphincter. A major part of diges-
Between adjacent villi are intestinal glands.
tion occurs in the' stomach, where hydrochloric acid
is secreted through the gastric mucosal glands under
the influence of the vagus nerve. The jejunum
The regions of the stomach include the cardiac, The name jejunum means "of no significance," and the \
fundic, corpus (body), and pyloric regions. The stom- jejunum is the second region of the small intestine. It
ach contains a right border (referred to as the lesser contains numerous mucosal villae but no submucosal
curvature) and a left border (the greater curvature). glands.
The mucosa consists of a lining of simple columnar It occupies roughly two-fifths of the remaining
epithelium and the lamina propria. It contains numer- small intestine and is located in the upper right zone
ous regionally presented gastric and mucous glands. of the infracolic region.
The muscularis of the stomach contains three
layers of smooth muscle. The lesser curvature of
the stomach is connected to the visceral surface of The ileum
the liver by a reflection of peritoneum called the The ileum is the terminal three-fifths of the small in-
hepatogastric ligament (lesser omentum). The greater testine and is situated in the lower right region of the
omentum connects the greater curvature to the trans- infracolic area, beyond the duodenum. Its submu-
verse colon. cosa contains numerous lymph nodules, which are
For clinical purposes, the esophageal hiatus of the referred to as Peyer's patches. It terminates at the
diaphragm is often the site of hiatal hernias of the ileocecal junction in the lower right quadrant of the
fundus and cardiac regions of the stomach that project abdomen.
up into the posterior mediastinum, thereby facilitating
gastric acid reflux into the esophagus and possible pre-
cancerous conditions. A vagotomy can be performed
large Intestine
to alleviate excessive or uncontrolled hydrochloric The large intestine is 1.5 meters long. It functions to
acid secretion through the gastric glands. remove water, store and compact fecal materials,
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and absorb vitamins. The large bowel contains no Selected Blood Supply to the Abdominal Viscera
villi, and the connective tissue between its numerous
intestinal glands is filled with many lymphocytes. The descending abdominal aorta contains three un-
The large intestine also contains mucosa, submucosa, paired branches:
muscularis externa, and serosa. The celiac trunk supplies the stomach and part
of the pancreas, liver, and duodenum.
Teniae coli The superior mesenteric artery supplies part of
the duodenum, jejunum, ileum, cecum, ascending
Both the large intestine and the small intestine con- colon, and transverse colon.
tain an inner layer of circular smooth muscle and an The inferior mesenteric artery supplies the
outer layer of longitudinally arranged smooth mus- descending and sigmoid colon.
cle. However, in the large bowel, the outer longitu-
dinal smooth muscle layer is sequestered into three
longitudinal columns called teniae coli. Teniae coli
contract to produce sacculation of the large intestine. 1'"8n The Central Nervous System
These sacculations are called haustra.
The central nervous system includes the brain and
the spinal cord. The nervous system consists of two
Regions of the colon types of cells: the neuron and neuralgia. Neurons are
Regions of the colon include the cecum; the appendix; responsible for producing an action potential. Types
the ascending, transverse, and descending colons; the of neurons include multipolar, pseudounipolar, and
sigmoid; the rectum; and the anus. bipolar.
The cecum is sac-like and is located in the lower
right quadrant. It is continuous with the ileum at the Neuron and Nerve Cell Processes
slit-like ileocecal valve.
The vermiform appendix is a worm-like divertic- Neurons contain a perikaryon (cell body of a mature
ulum of the cecum and is attached to the cecum's neuron) and two types of cytoplasmic cellular exten-
medial and posterior surface. It is filled with lymph sions or processes: axons and dendrites.
nodules and lymphocytes. Axons are long nerve cell processes of uniform
The ascending colon is retroperitoneal and is lo- diameter that generally carry efferent neuronal activity
cated on the right side of the infracolic region, away from the cell body to other neurons or effector \
where it is directed cranially to its termination at organs such as the muscle cell. Axons may be myeli-
the right colic flexure at about L3. The right colic nated or nonmyelinated. Myelin is a protein-fatty insu-
flexure is the location where the ascending colon lating material. The action potential of myelinated
makes an abrupt turn to the left to become the trans- axons is faster than that of nonmyelinated axons.
verse colon. Dendrites are shorter, branching neuronal pro-
The transverse colon is a horizontally directed cesses that generally receive nerve impulses from
continuation of the ascending colon at the right colic other cells through synaptic junctions.-
flexure. It forms an abrupt downward turn in the left The change of the resting potential to the action
upper abdominal quadrant as the left colic (splenic) potential of the axon is facilitated by the movement
flexure in the region of the spleen and left kidney. The of sodium and potassium ions through gated sodium
transverse colon is connected to the greater curvature and potassium channels on the surface of the plasma
of the stomach by several layers of visceral peritoneal membrane of the axon.
reflections called the greater omentum.
The descending colon is also retroperitoneal and
directed inferiorly along the left wall of the abdomi-
The Synapse
nal cavity until it reaches the pelvic brim to become Related neurons make connections .to one another
the sigmoid colon. through specialized cell-to-cell contacts called syn-
The sigmoid colon is sinuous (S shaped) and de- apses. In general, the axon terminal of one neuron
scends to the pelvis. It enters the left aspect of pelvic synapses on the cell body or dendrites of another
brim, where it ultimately terminates. neuron. The neuronal synapse is the point of contact
The terminal region of the large intestine consists between neurons in which an action potential is
of the rectum and anus. transmitted from one nerve cell to another.
Anatomy and Physiology

Neurotransmitters The frontal/abe


The frontal lobe is separated from the parietal lobe
The axon terminal of a given cell releases membrane- by the vertically oriented central sulcus. The frontal
bound packages of chemicals called neurotransmit- lobe functions to provide higher cortical activity or
ters into the synaptic cleft. The cell membrane of the mental integration.
adjacent, stimulated cell dendrite contains receptors
that can be activated by the neurotransmitter to create The parietal/abe
an action potential in the second neuron, thus facili- The parietal lobe is located laterally on the cerebral
tating transneuronal action potential generation. cortex and is found between the vertically oriented
A large array of neurotransmitters exists in the central sulcus and the postcentral parieto-occipital
nervous system, such as acetylcholine, y-arninobutyric sulci. Between the precentral and postcentral sulci are
acid (GABA), and serotonin. Anesthetic function may similarly located the precentral gyrus, central sulcus,
be facilitated by blocking neurotransmitter release at and postcentral gyrus.
the neuronal synapse. The precentral gyrus is motor in activity and sends
Glial cells are generally smaller nerve cells. They descending axonal fibers through the basal ganglia,
are mechanically and metabolically supportive and internal capsule, tegmentum of the mesencephalon,
protective of neurons. Types of glial cells include ventral pons, and pyramids of the medulla, where
astrocytes, oligodendrocytes, microglia, and ependy- they cross to the opposite side of the brain before ter-
mal cells. minating on to the ventral horn gray matter of the
spinal cord where they ultimately synapse on ventral
The Brain horn lower motor cells. Ventral horn motor cells, in
turn, send myelinated axons though spinal nerves to
The brain is that part of the central nervous system synapse on skeletal muscles of the body.
located in the cranium. It can be organized and sub- The postcentral gyrus is sensory (afferent) in func-
divided into several developmental, morphological, tion and receives the modalities of pain, temperature,
and functional regions. Regions of the developing and tactile (touch) from the skin, joints, and muscle
mammalian brain include the telencephalon, the di- and tendon spindles from peripheral nerve receptors.
encephalon, the mesencephalon, the metencephalon, The peripheral nerve receptors send such sensations
and the myencephalon. upward through the spinal nerve, dorsal roots, as-
cending tracts of the spinal cord, medulla, pons, mes- ~
The telencephalon encephalon, and internal capsule and finally to the
cortex of the postcentral gyrus, where they synapse
The telencephalon (neocortex) consists of the cere- and are consciously appreciated.
bral cortex and the deep telencephalic nuclei (basal Reading comprehension and auditory elucidation
ganglia). are also associated with supramarginal, associated
temporal gyri and angular gyri of this lobe. The loss
The cerebral cortex of such abilities is termed dyslexia and aphasia.
The cerebral cortex is made up of an outer layer of
gray matter (neurons and glial cells) and an inner The temporal/abe
layer of deep white matter (glial cells and myelinated The temporal lobe functions in language, memory,
axonal fibers). The outer gray cortical layer consists and auditory information processing. It contains the
of six alternating and connecting cellular and synap- deep gray matter amygdala nucleus. This structure is
tic laminae. The cerebral cortex is convoluted and an important emotional center and is closely associ-
has many bump-like gyri and shallow groove-like in- ated with the hippocampus, an important learning
dentations referred to as sulci. and memory module.
The cerebral cortex is divided into several lobes The temporal lobe contains two horizontally di-
that are designated and named according to over- rected sulci, the superior and inferior temporal sulci,
lying cranial bone: the frontal, parietal, temporal, and two similarly oriented gyri, the superior and
occipital, and limbic lobes. The various lobes are middle temporal gyri.
separated by regularly occurring sulci (shallow
grooves) or fissures (deeper grooves). Each cerebral The occipita/lobe
hemisphere contains a cerebrospinal fluid-filled The occipital lobe is the most posteriorly situated
cavity called a lateral ventricle. lobe. It is separated from the parietal lobe by the
The APhA Complete Review for the Foreign Pharmacy Graduate Equivalency Examination®

parieto-occipital fissure and also contains the cal- The tectum


carine fissure and lingual gyrus. The occipital lobe The tectum represents the roof of the mesencephalon
is considered a primary and secondary visual center and contains two bump-like swellings of subsurface
where light comes into consciousness. gray matter called the superior and inferior colliculi.
The superior colliculus is a relay center for visual re-
The limbic lobe flexes. The inferior colliculus is a synaptic center for
The limbic lobe is situated on the medial aspect of the auditory reflexes. Between the tectum and tegmen-
cerebral cortex and consists of the cingulated sulcus tum is the cerebral aqueduct, which contains cere-
and gyrus that are situated dorsal to the corpus cal- brospinal fluid.
losum. It is closely related to the amygdala and is
concerned with emotional expressions such as fear, The tegmentum
aversion, and attraction. The tegmental floor of the mesencephalon contains
the red nucleus (nucleus ruber) and the black nucleus
The deep telencephalic nuclei (substantia nigra). Diseases of the substantia nigra
The deep telencephalic nuclei consist of profoundly produce a motor instability called Parkinson's disease.
situated islets of gray matter (called nuclei) located The tegmentum also contains several motor and
within the deep white matter of the cerebral cortex. sensory nuclei related to the cranial nerves, such as
Historically, they have been referred to as the basal the oculomotor and trochlear. It is represented ven-
ganglia. Selected deep telencephalic nuclei include trally by two bundles of descending motor axon
the caudate nucleus, the putamen, and the globus bundles, originating from the cortex, called the crus
pallidus. cerebri.
Such clusters of neurons are concerned with motor
and premotor movements and initiation of motor
movement. Dysfunctions of this system include
The pons
Parkinson's and Huntington's diseases. The word pons means bridge, and the pons connects
the midbrain (mesencephalon) and the medulla ob-
longata. The trigeminal nerve connects to the lateral
The diencephalon surface of the pons, and it has important connections
The diencephalon (or in-between brain region) is to the cerebellum, mesencephalon, and medulla.
located in the gray matter of the lateral wall of the This region contains a mixture of ascending fibers
third ventricle. It is subdivided into the dorsal thala- of various origins called the reticular formation and
mus and hypothalamus. major motor and sensory nuclei in addition to im-
The dorsal thalamus is an important synaptic cen- portant ascending and descending axonal pathways.
ter that receives axons ascending from lower levels to
the cerebral cortex. It also projects other cell fibers,
which originate from the cerebral cortex, in descend-
The medulla oblongata
ing pathways to lower levels of the brain stem and The medulla oblongata is the caudal-most compo-
spinal cord. Pain comes into consciousness at tha- nent of the brain stem. It contains nuclei that are
lamic levels. related to control of cardiac function and respira-
The hypothalamus is situated ventral to the dorsal tion. Developmental defects of this nuclear com-
thalamus; is closely related to the pituitary gland; and plex have been implicated in sudden infant death
functions to regulate a plethora of hormones and sev- syndrome.
eral visceral activities such as appetite, thirst, sex drive, The medulla oblongata contains many motor
electrolyte balance, and blood sugar. Malfunctions of and sensory nuclei associated with cranial nerves.
the hypothalamus have been suggested in anorexia Ascending axons carrying sensory information from
nervosa, obesity, and precocious puberty. cervical and lumbar spinal cord levels synapse on
the gracilis and cuneatus nuclei, and descending
motor axons cross to the opposite side in the motor
The mesencephalon decussations.
The mesencephalon is that region between the dien- The glossopharyngeal, vagus, and spinal accessory
cephalons and the pons. It contains a roof called the cranial nerves are attached to the medulla oblongata,
tectum (superior and inferior colliculi) and a floor which contains important sensory relay nuclei that
called the tegmentum (cerebral peduncles). send axons to the thalamus and cortex.
Anatomy and Physiology

Cranial Nerves factors), which stimulate other ductless glands to


increase or decrease their hormonal production.
Twelve pairs of cranial nerves are attached to the Subdivisions of the pituitary gland include the ade-
brain. Some are purely sensory and receive only affer- nohypophysis and the neurohypophysis. Hormones
ent information. Other cranial nerves are all motor produced by the anterior pituitary (adenohypophysis)
and provide efferent impulses to effector organs such include follicular-stimulating hormone, thyrotrophic-
as skeletal, cardiac, ·and smooth muscles and glands. stimulating hormone, growth hormone (somato-
Several are mixed and both provide motor output to trophic hormone), luteinizing hormone, interstitial
effector organs and receive sensory information from cell-stimulating hormone, prolactin, and adrenocorti-
peripherally situated receptors. cotrophic hormone. Hormones of the posterior lobe
Cranial nerves are designated by Roman numerals: (neurohypophysis) include vasopressin and oxytocin.
olfactory (I), optic (II), oculomotor (III), trochlear
(IV), trigeminal (V), abducens (VI), facial (VII), audi-
tory (VIII), glossopharyngeal (IX), vagus (XI), spinal The Thyroid Gland
accessory (XI), and hypoglossal (XII). The thyroid gland is well encapsulated by connective
tissue, is bowtie shaped, and consists of two lateral
The Spinal Cord lobes and a connecting region or isthmus. It is located
in the anterior neck region anterior to the trachea.
The spinal cord is connected cephalically to the brain Thyroid-stimulating hormone is released from the
by the medulla oblongata in the region of the fora- anterior lobe of the pituitary into the bloodstream,
men magnum and extends caudally to the level of the where it travels to the thyroid gland and stimulates it
second lumbar vertebra. It consists of an outer layer to produce thyroxin and calcitonin.
of white matter and an inner core of gray matter. The structural unit of the thyroid gland is the thy-
Deep to the gray matter is a space housing cere- roid follicle. Thyroid follicle cells secrete thyroxin
brospinal fluid called the central canal. The deeper into the colloid substance, where it is stored for fu-
gray matter can be organized physiologically into ture release into the bloodstream. Thyroxin regulates
sensory dorsal horn and ventral motor horn regions. general cell metabolism.
Thoracic regions of the spinal cord gray matter con-
tain a lateral horn that contains motor cells involved
The Parathyroid Glands
in the sympathetic division of the autonomic nervous
system. The spinal cord contains several reflex path- Parathyroid glands are located in the connective tissue
ways for movement of the extremities. capsule on the posterior aspect of the thyroid gland.
Thirty-one pairs of spinal nerves are attached bilat- Parathyroid glands (usually four) secrete parathyroid
erally to the spinal cord. More distally, each pair of hormone, which regulates the amdunt of calcium in
dorsal and ventral roots unite to form a single mixed the bloodstream.
(sensory-motor) spinal nerve. Dorsal root fibers are
efferent or sensory. In general, dorsal roots contain a The Suprarenal Gland
dorsal root (sensory) ganglion. Ventral root fibers are
motor or efferent. The suprarenal (adrenal) gland is triangular shaped
and is situated on the cranial aspect of each kidney.
It contains an outer cortical region and an inner
medullary zone. The adrenal cortex secretes glu-
1'"9m The Endocrine System
['":-:."2/.0:::::::"A::~-_,_ L'' ;~::-_-Y.,'
cocorticoids, mineralocorticoids, and androgens.
Glucocorticoids control the level of glucose in the
The endocrine system consists of ductless glands that blood plasma, mineralocorticoids effect the metabo-
secrete hormones directly into the bloodstream. The lism of inorganic salts, and androgens influence sex-
major endocrine glands are the pituitary gland, the ual expression and drive. Cells of the adrenal medulla
thyroid gland, the parathyroid glands, the suprarenal are neuronal in appearance and secrete the hormones
gland, and the ovaries (testes in the male). epinephrine (adrenaline) and norepinephrine.

The Pituitary Gland The Ovaries


The pituitary gland has classically been called the The ovary is an endocrine gland in that its cortex
master gland because it releases hormones (releasing contains ovarian follicles, which are made up of thecal
. The APhA Complete Review for the Foreign Pharmacy Graduate Equivalency Examination®

and follicular cells. The ovarian follicle secretes es- terone. Testosterone is responsible for the manifesta-
trogen and progesterone during the ovarian cycle. tion of secondary sex characteristics in the male and
Both estrogen and progesterone are functional in is produced and released by the interstitial cells of
facilitating the uterine cycle. Estrogen is responsible Leydig, which are located in the highly vascular con-
for sexual maturity of the female body. Progesterone nective tissue of the testes.
maintains the lining of the uterus during pregnancy. Accessory structures of the male reproductive
At puberty, primary follicles develop into growing system include the following:
follicles, under the influence of follicle-stimulating
!ill In the vas deferens, sperm cells migrate to the
hormone from the anterior lobe of the pituitary gland,
and they release a mature ovum every 14 to 15 days epididymis, where they mature and are activated.
of the ovarian cycle. 121 The seminal vesicles are glands that secrete sug-
ars, which nourish the sperm in the male repro-
ductive tract.
The ejaculatory ducts are tubules that traverse the
1.. 10& The Urinary System 111
prostate gland and direct sperm into the urethra.
f;;;l The prostate gland is a mJicous-secreting, pear-
Components of the urinary system include the kid-
shaped structure that is located at the neck of the
neys, the ureter, the bladder, and the urethra.
bladder, where it surrounds the urethra.
The kidneys are bean-shaped organs that are lo-
cated anterior to the 11 and 12 ribs of the posterior The Cowper's glands are located in the perineum,
abdominal region within the extraperitoneal fatty where they produce an oily secretion.
connective tissue and deep to the peritoneum. Each
kidney contains a medially directed, concave-like The Female Reproductive System
hilus, which receives the renal pelvis, renal veins, and
branches of the renal artery. The female reproductive system consists of the ovaries,
Components of the renal cortex are the renal fallopian (uterine) tubes, uterus, vagina, labia majora,
corpuscle, the proximal convoluted tubules, and the labia minora, and clitoris.
distal convoluted tubules. Components of the renal The ovaries are the primary organs of female repro-
medulla include Henle's loop and collecting ducts. duction. They are located internally in the pelvis and
The renal pelvis is funnel shaped, and its apex nar- can be subdivided into an inner medulla and an outer
rows and connects to the ureter. The ureter directs · cortex. The ovarian cortex contains germ cells, which
urine to the bladder, where it is stored and released are located in cellular enclosures called follicles.
through the urethra to the environment. The ovarian cycle can be summarized as follows:
The tubular nephron is the excretory part of the r:~ Mature follicular cells (and associated thecal
kidney (producing ultrafiltrate). It consists of the cells) secrete female sex hormones in response to
following discernable subunits: renal corpuscles, the presence of follicle-stimulating hormone from
the proximal convoluted tubule, the proximal straight the anterior pituitary gland.
tubule, the thin segment of Henle's loop, the thick [l':l Estrogen and progesterone are the. primary
ascending straight tubule, and the distal convoluted female sex hormones produced by sexually
tubule. mature ovaries.
The kidneys are supplied bilaterally with blood !Ell At puberty, primitive follicles begin to develop
through renal arteries from the descending abdomi- into mature follicles containing mature ovum
nal aorta. The renal vein is a tributary of the inferior or eggs.
vena cava. lfJl A mature ovum is released each month during
the midpoint of the female ovarian-menstrual
cycle of 28-30 days.
1..11 The Reproductive System
m
The buildup, subsequent deterioration, and final
The Male Reproductive System shedding of the uterine endometrium is called the
uterine cycle and is facilitated and coordinated by the
Components of the male reproductive system include rise and fall of estrogen and progesterone in the ovar-
the testes, scrotum, and penis. The testes are the pri- ian cortex.
mary sex organs of the male reproductive system, and Modern oral contraceptive technology is based on
they are housed in the scrotum. They serve to pro- the chronic presence of high levels of female hor-
duce spermatozoa and the male sex hormone testos- mones that prevent ovulation.
Anatomy and Physiology

1·12. Body Fluids and Electrolytes fi1 Hypercalcemia is a condition of high calcium. It
~~:E::-::-:;',::;~.r;;:.~-,TC:.·:"!t-"'- __ _
can result from a high level of parathyroid hor-
Electrolytes are charged minerals found in body flu- mone or from bone cancer.
ids. Common electrolytes include sodium, potassium,
calcium, chloride, and phosphate. Generally, elec-
trolytes are obtained from foods and liquids that are 1. .13 . Cell Structure, Organization,
ingested as part of the normal diet.
Normal electrolyte levels are maintained by the and Physiology
f'\-"Y~fO(";";Wf~i';J;:~;::;;,2;:'Z~~-;.~~-;> _,; ~

kidney (excretion) and the GI tract (absorption).


The normal level for a given electrolyte can become There are three types of living units: prokaryotic
elevated or depressed because of disease, medica- cells, eukaryotic cells, and viruses.
tion, or an abnormal diet. Prokaryotic cells are those that lack a membrane-
bound nucleus. This cell type contains DNA (deoxyri-
bonucleic acid), which is organized into circular loops
Overhydration and Dehydration called plasmids. Bacteria and blue-green algae are ex-
The amount of body fluid and its electrolyte content amples of prokaryotic cells. They are generally round,
constantly changes because of urination, sweat- rod shaped, or spiral shaped; divide by binary fission;
ing, vomiting, hormonal regulation, defecation, and and are only 1-2 micrometers in diameter.
hemorrhage. Eukaryotic organisms have nuclear materials that
Overhydration is a condition in which too much are bound by membranes (nuclear membranes), and
water is located in the body (blood vessels or connec- they can be subdivided into animal and plant cells.
tive tissue), resulting in swelling or edema. Eukaryotic cells also contain small intracellular,
Dehydration is the reverse condition of over- organ-like structures referred to as organelles.
hydration and is characterized by too little water in Viruses consist of nucleic acids surrounded by a
tissue fluid and blood vessels. Dehydration can lead protein covering or shell.
to low blood pressure and can compromise the body's Cellular organelles include the nucleus, mitochon-
ability to sweat. It may lead to mental confusion and dria, endoplasmic reticulum (smooth and rough),
disorientation. It may be treated by the oral or intra- vesicles, centrioles, lysosomes, and chloroplasts.
venous provision of water and electrolytes. Chloroplasts and the cell wall are found only in plant
cells.
Electrolyte Nomenclature
The following terminology is associated with elec- The Cell Membrane
trolytes: · The cell membrane consists of a lipid bilayer studded
!l!l The prefix hypo- indicates not enough or too by transmembrane proteins, which may be involved
little of a given electrolyte, and the prefix hyper- in the transportation of materials into and outside of
represents too much of a given electrolyte. the cell. Integral proteins are transmembrane pro-
!!!l Kalemia denotes potassium, and natremia teins that may act as channels for the transportation
denotes sodium. of ions and water. Peripheral proteins are located on
lf!l Hyponatremia is a low level of sodium, whereas the cytoplasmic side of the cell membrane and may
hypernatremia is a high level of sodium. be involved in maintaining the cell shape.
rn~ Hypokalemia is a condition in which the potas- Integral proteins are attached to carbohydrates that
sium level is low and may be the result of the use extend from the external surface of the cell membrane
of diuretics, which cause the kidneys to excrete as a fuzzy coat or glycocalyx.
excess potassium.
ail Hyperkalemia is a condition in which potassium
The Nucleus
is high. It is caused by the administration of med-
ications that reduce the amount of potassium ex- The nucleus is a porous, double-unit membrane-
creted by the kidneys or the overuse of potassium bound structure generally located at the center of the
supplement medication. cell. It stores, transfers, and expresses genetic infor-
!ilil Hypocalcemia is a condition of low calcium. This mation required for protein synthesis necessary for
condition can result from the low production of the morphology and function of the cell. It contains
parathyroid hormone or low levels of vitamin D. DNA-protein strands called chromatin\
The APhA Complete Review for the Foreign Pharmacy Graduate Equivalency Examination®

Chromatin may exist as euchromatin (active filaments


and thin) or heterochromatin (inactive and con-
Filaments are protein strands or tubes that form the
densed). Chromatin condenses during cell division
cytoskeleton and certain contractile elements of the
to form chromosomes. See Chapter 6 for addi-
cell (actin and myosin).
tional information.

The nucleolus Microtubules


Microtubules form the mitotic spindle.
The nucleolus consists of RNA (ribonucleic acid),
DNA, and protein and is involved in ribosome pro-
duction. It is located within the nucleus and is not Vesicles
bound by a unit membrane.
Vesicles are surrounded by a single membrane and
are involved in storage and secretion.
Ribosomes
Ribosomes are special units of rRNA (ribosomal Centrioles
RNA) and protein that are formed in the nucleus but
Centrioles consist of several tubular structures that
perform their activity in the cytoplasm. They are non-
produce other microtubules and are highly active in
membrane-bound structures that are involved in the
cell division and maintenance of the cytoskeleton.
translation of mRNA (messenger RNA) into protein.
Free ribosomes are located in the cytoplasm and
are not associated with the endoplasmic reticulum. Cell Adhesions
Ribosomes may also be located on the surface of the
Types of cell adhesions include the following:
endoplasmic reticulum.
li1l Tight junctions are locations between cells where
there is little or no space.
The Endoplasmic Reticulum
tl!l Gap junctions are protein bridges between cells
The endoplasmic reticulum is a single membrane that form conduits for the passage of cytosol
structure that may or may not contain ribosomes on from one cell to another.
its surface. When its membranes are devoid of ribo- !1l Desmosomes are proteins in adjacent intercellu-
somes, it is called the smooth endoplasmic reticulum lar and extracellular spaces.
and is often involved in lipid metabolism. When
it contains ribosomes on its membranes, it is called
rough endoplasmic reticulum and is involved with 1..14a Key Points
protein translation. ~'1t"S.~~::--z-::;,•::::~-Ij,C:.<>.,

The Integument System


The Golgi Complex lil The skin serves to cool and rid the body of toxic
The Golgi complex consists of a stack of flattened waste through the secretion, excretion, and evap-
membranes and vesicles that sort various protein oration of sweat from sweat glands. It also pro-
and carbohydrate complexes. tects the body from desiccation and mechanical
abrasion.
~ The skin is highly absorptive and facilitates the
Mitochondria uptake of topically applied medications, such as
Mitochondria are round or elongated double-walled salves and ointments.
membrane structures involved in energy production rii Subcutaneous medications may be administered
as ATP. Mitochondria contain DNA in the form of to vascular-rich deep connective tissue through
mitochondrial genes. hypodermic injections.

Lysosomes Muscular System


Lysosomes are enzyme-filled vesicles bound by a sin- [ij Skeletal muscle cells are voluntary and highly
gle membrane that facilitate intracellular digestion of involved in movement of the skeleton and the
proteins and carbohydrates. musculoskeletal system. \
Anatomy and Physiology Y1\JJ

lilll Skeletal muscle cells are multinucleated rectangu- !i1ll The flat, plate-like squamous cells of the in-
lar or cigar-shaped structures and are contained tima facilitate the flow of blood and prevent
by a cell membrane called the plasmalemma or clotting. Mechanical damage or the accumula-
sarcolemma. tion of calcium and fatty deposits in the intima
1m Cardiac muscle cells are striated, are involuntary, may cause blood clots, which may cause cere-
and are found in' the heart. They are responsible bral accidents (strokes) and coronary artery
for contraction of the heart. heart disease.
1m Smooth muscle is located in the walls of hollow ~& The media consists of a layer of smooth muscle
organs, such as the stomach, intestines, bladder, and is thickest in arteries. The adventitia is wider
blood vessels, and uterus. or thicker in veins. The smooth muscle cell media
!i1ll The Sliding Filament Theory of Muscle Contrac- of arteries tends to be arranged in several circular
tion suggests that thick and thin myofilaments layers.
interdigitate and slide between and with one fJil The adventitia is an outer layer of predominately
another during muscle contraction. Calcium and connective tissue. Arterial types include large ar-
adenosine-5'-triphosphate are vital in producing teries, medium arteries, small arteries, and arteri-
muscle contraction. oles. Types of veins include large veins, medium
!i1ll Skeletal muscle fibers require neuronal input to veins, small veins, and venues.
contract or act. Efferent axons terminate on !h'l Capillaries consist of an endothelial lining sur-
skeletal muscle cells at specialized synaptic sites rounded by a connective tissue intima.
of contact called motor end plates or the neuro-
muscular junction.
Ill The motor end plate synapse is where the axon The heart
terminal releases a neurotransmitter (usually rn The heart is a modified blood vessel that functions
acetylcholine) into the synaptic cleft. to pump blood to various parts of the body.
Ill Specialized receptors are located on a plasma
!i1ll The human heart consists of four primary cham-
membrane of the muscle cell that can be ener-
bers: the right and left atria and right and left
gized by the neurotransmitter to produce an
ventricles.
axon potential in the muscle cell.
The great blood vessels of the heart include veins
that bring deoxygenated blood to the left atrium
Skeletal System and arteries that carry deoxygenated and oxy-
genated blood away from the heart. These veins
Ill The bony skeleton of the human is internally
include the superior vena cava, inferior vena
located and provides protection from mechanical
injury and attachment for muscles. It stores and, cava, and coronary sinus.
!iii The synchronous contraction of right and left
when necessary, releases calcium and other vital
inorganic salts; is instrumental in blood forma- atria before that of right and left ventricles is pro-
tion through bone marrow; and acts as scaffold- vided by the cardiac conduction system.
ing in overcoming gravity. rn The cardiac conduction system consists of modi-
!i1l Bones can be classified as short, long, irregular, fied cardiac muscle fibers that are specialized for
and flat. They are attached to one another by conducting fast nerve-like impulses in cardiac tis-
joints. sue. These fibers facilitate the synchronous con-
El Strong dense regular connective tissue bands traction of atria before ventricles.
called ligaments generally hold joints together.
Electrical activity of the heart
The Cardiovascular System &JJ An electrocardiograph tracing has three compo-
!i1ll The cardiovascular system is an enclosed entity. nents or waves: the P wave, QRS wave complex,
rH The system includes the heart, arteries, capillaries, and Twave.
and veins. Ell The P wave occurs with atria depolarization
(contraction).
R3 The QRS wave complex represents depolariza-
The tissue organization and types of blood vessels
tion of the ventricles (contraction).
!i1ll Blood vessels are generally organized into three The T wave represents electrical activity (repolar-
tissue layers: intima, media, and adventitia. ization) or relaxation of the vent'?icles.
The APhA Complete Review for the Foreign Pharmacy Graduate Equivalency Examination®

The lymphatic System II The nervous system consists of two types of cells:
the neuron and neuralgia. Neurons are responsi-
The lymph nodes, spleen, thymus gland, and
ble for producing an action potential. Types of
tonsils produce lymphocytes, which contain
neurons include multipolar) pseudounipolarJ
macrophage-like, phagocytic lymphatic cells.
and bipolar.
These cells engulf and destroy invasive micro-
bial cells.
The thymus gland is the source of thymic lym- The synapse
phocytes (T-lymphocytes), which, after matu-
l:i'l Related neurons make connections to one an-
rity, are distributed to other lymphatic organs.
other through specialized cell-to-cell contacts
The spleen is the largest lymph organ of the
called synapses.
body and also functions to store and destroy
II The axon terminal of a given cell releases
old red blood cells.
membrane-bound packages of chemicals called
neurotransmitters into the synaptic cleft. The
The Respiratory System cell membrane of the adjacent, stimulated cell
The function of the respiratory system is to filter, dendrite contains receptors that can be activated
humidify, and transmit air to the lungs, where it by the neurotransmitter to create an action
oxygenates blood. The nasal cavity filters and potential in the second neuron, thus facilitating
conditions the aspired air. transneuronal action potential generation.
The pharynx, larynx, trachea, bronchi, and bron-
chioles transmit air to the lungs, where the respi- The brain
ratory system oxygenates the blood through thin-
walled pulmonary alveoli and alveolar sacs. l:i'l The brain can be subdivided into the following
The pulmonary alveolus consists of a single layer regions: telencephalon (cerebral cortex and basal
of simple squamous epithelium (pulmonary ep- ganglia), diencephalon, mesencephalon, pons,
ithelium), which is adjacent to a basement mem- and medulla oblongata.
brane and abuts against another layer of simple ~ The cerebral cortex is convoluted and has many
squamous epithelium (endothelium) of a capil- bump-like gyri and shallow groove-1ike indenta-
lary. This layer is referred to as the blood-air tions referred to as sulci.
barrier. 11 The cerebral cortex is divided into several lobes
that are designated and named according to over-
lying cranial bone: the frontal, parietal, temporal,
The Digestive System Proper occipital, and limbic lobes.
E1 Organs of the digestive system include the oral rid! Functional specificity is associated with lobes of
cavity (teeth, tongue, and salivary glands); the the cerebral hemisphere, and they are associated
esophagus; the stomach; the small and large with fluid-filled cavities called ventricles.
intestines; the rectum; and the anus. UJ Basal ganglia consist of profoundly situated islets
Eel Accessory glands of digestion include the sali- of gray matter (called nuclei) located within the
vary glands, the liver, the gall bladder, and deep white matter of the cerebral cortex. Selected
the pancreas. deep telencephalic nuclei include the caudate
Digestion begins in the oral cavity or mouth, nucleus, the putamen, and the globus pallidus.
where coarse and complex carbohydrates are
broken down into smaller particles and mixed
The brain stem
with saliva (containing salivary amylase), which
transforms them into simpler carbohydrates. ill! The brain stem includes the diencephalon, mesen-
Mastication breaks down large chunks of animal cephalon, pons, and medulla oblongata.
and plant food materials (proteins, fats, and car- rid! The tegmental floor of the mesencephalon con-
bohydrates) into smaller units. tains the red nucleus (nucleus ruber) and the
black nucleus (substantia nigra).
II Diseases of the substantia nigra may produce a
The Central Nervous System motor instability called Parkiru;on's disease.
II The central nervous system includes the brain II The medulla oblongata contains nuclei that are re-
and the spinal cord. lated to control of cardiac function and respiration.
Anatomy and Physiology

The Endocrine System The renal corpuscle filters the blood to produce
!ill
ultrafiltrate containing nitrogenous compounds,
lffil The endocrine system consists of ductless glands
glucose, electrolytes, and water.
that secrete specific hormones directly into
m The water, glucose, and electrolytes are reab-
the bloodstream. They comprise the following
sorbed by vascular-rich connective tissue,
glands: pituitary, thyroid, parathyroid,
which encloses the remaining nonrenal
suprarenal, ovary, and testis.
corpuscle components of the nephron
ff1 The pituitary gland has classically been called
and collecting ducts.
the master gland because it releases hormones
(releasing factors), which stimulate other duct-
less glands to increase or decrease their hor- The Male Reproductive System
monal production.
Components of the male reproductive system
til Subdivisions of the pituitary gland include the include the testes, scrotum, and penis.
adenohypophysis and the neurohypophysis.
The testes are the primary sex organs of the
Hormones produced by the anterior pituitary male reproductive system, and they produce
(adenohypophysis) include follicular-stimulating spermatozoa and the male sex hormone
hormone, thyrotrophic-stimulating hormone,
testosterone.
growth hormone (somatotrophic hormone), Testosterone is responsible for the manifestation
luteinizing hormone, interstitial cell-stimulating
of secondary sex characteristics in the male.
hormone, prolactin, and adrenocorticotrophic
hormone.
Hormones of the posterior lobe (neurohypophy- The Female Reproductive System
sis) include vasopressin and oxytocin. The female reproductive system consists of
the ovaries, fallopian (uterine) tubes, uterus,
The Urinary System vagina, labia majora, labia minora, and
clitoris.
till Components of the urinary system include
The ovaries are the primary organs of female
the kidneys, the ureter, the bladder, and the
reproduction. They are located internally in
urethra.
the pelvis and can be subdivided into an inner
!\l'J The kidneys are bean-shaped organs that
medulla and an outer cortex. The ovarian
are located along the posterior abdominal cortex contains germ cells, which are located
wall. Each kidney contains a medially directed, in cellular enclosures called follicles.
concave-like hilus, which receives the renal
pelvis, renal veins, and branches of the renal
artery. Body Fluids ami Electrolytes
IT1 Components of the renal cortex are the renal Electrolytes are charged minerals found in body
corpuscle, the proximal convoluted tubules, fluids. Common electrolytes include sodium,
and the distal convoluted tubules. Components potassium, calcium, chloride, and phosphate.
of the renal medulla include Henle's loop and Generally, electrolytes are obtained from foods
collecting ducts. and liquids that are ingested as part of the nor-
0 The renal pelvis is funnel shaped, and its mal diet.
apex narrows and connects to the ureter. The Normal electrolyte levels are maintained by
ureter directs urine to the bladder, where it is the kidney (excretion) and the GI tract
stored and released through the urethra to the (absorption).
environment. The normal level for a given electrolyte can be-
!ill The tubular nephron is the excretory part of come elevated or depressed because of disease,
the kidney (producing ultrafiltrate), and it medication, or an abnormal diet.
consists of the following discernable subunits:
renal corpuscles, the proximal convoluted
tubule, the proximal straight tubule, the thin Cell Structure, Organization, and Physiology
/
segment of Henle's loop, the thick ascending llli Cellular organelles are intracellular organ-like
straight tubule, and the distal convoluted structures that include the cell membrane, nu-
tubule. cleus, mitochondria, endoplasmic reticulum
.. The APhA Complete Review tor the Foreign Pharmacy Graduate Equivalency Examination®

(smooth and rough), vesicles, centrioles, lyso- 7. The sinoatrial node (natural pacemaker) is lo-
somes, and chloroplasts. cated in which of the following regions?
Chloroplasts and the cell wall are found only in
A. Right atrium
plant cells.
B. Right ventricle
C. Left atrium
D. Left ventricle
1..15m Questions
8. Which of the following is not a lymphatic
1. Which of the following is the outermost layer
organ?
of the skin's epidermis?
A. Spleen
A. Stratum corneum
B. Thymus gland
B. Dermis
. C. Tonsil
C. Stratum basale
D. Hypodermis D. Cecum

9. Digestion of carbohydrates begins in which of


2. The I-band of skeletal muscle contains which
the following regions?
of the following myofilaments?
A. Sigmoid colon
A. Myosin
B. Stomach
B. Actin
C. Duodenum
C. Tubulin
D. Mouth
D. Collagen
10. Which of the following is a large blood
3. Long bones are usually covered on the surface
vessel that delivers deoxygenated blood
by a highly vascular, dense connective enve-
to the liver?
lope. Which of the following terms describes
this envelope? A. Splenic artery
B. Portal vein
A. Periosternum
C. Thoracic duct
B. Endosteum
D. Celiac trunk
C. Dura mater
D. Synapse
11. Which of these glands is both endocrine and
4. Which of the following is not a bone cell? exocrine in function?

A. Osteocyte A. Pancreas
B. Osteoblast B. Thymus gland
C. Osteoclast C. Adrenal gland
D. Glial cell D. Pituitary gland

5. The intervertebral disc is located in which 12. Which of the following kidney structures is
of the following regions of the body? not a Gomponent of the nephron?

A. Stomach A. Renal corpuscle


B. Sternum B. Proximal convoluted tubule
C. Bony spine C. Henle's loop
D. Epidermis of the skin D. Collecting duct

6. The superior vena cava empties deoxygenated 13. Which of the following is a neurotransmitter
blood into which of the following regions that is released from the axon terminal of the
of the heart? neuromuscular junction?
A. Estrogen /
A. Right atrium
B. Right ventricle B. Substance P
C. Left atrium C. Acetylcholine
D. Left ventricle D.GABA
Anatomy and

14. The ovarian follicle produces and secretes 1..16 . Answers


which of the following hormones? ~"'\B'..Q~~.;;;::IoC;~"'l~...i~"-'_cc,:• -~--.'

A. Testosterone 1. A. The stratum corneum is the outermost layer.


B. Estrogen The dermis, stratum basale, and hypodermis
C. Growth hormone are all lower levels of the skin.
D. Follicle-stimulating hormone (FSH) 2. B. The protein actin is the main myofilament in
the !-band of skeletal muscle.
15. Which of the following regions of the brain is 3. A. The periosternum covers the surface of long
responsible for higher integration, planning, bones.
and thinking? 4. D. Glial cells are located in the brain and help
to maintain the other neuronal cells.
A. Frontal lobe
B. Occipital lobe 5. C. Intervertebral discs are a component of the
C. Thalamus bony spine. The sternum is also a component
D. Medulla oblongata of the skeleton, but is located in the chest and
is a component of the rib structure.
16. Gaseous 0 2 and C0 2 are exchanged in which 6. A. Deoxygenated blood from the body is de-
level of the respiratory system? livered to the right atrium by the superior
vena cava.
A. Trachea 7. A. The sinoatrial node is located in the right
B. Bronchi atrium.
C. Pulmonary alveoli 8. D. The spleen, thymus gland, and tonsils are all
D. Larynx part of the lymphatic system. The cecum is part
of the colon.
17. Which of the following has classically been 9. D. The enzyme amylase is secreted in the mouth
called the master gland? and begins the digestion of carbohydrates.
A. Adrenal gland 10. B. The portal vein delivers deoxygenated
B. Thyroid gland blood and nutrients from the GI tract to the
C. Pancreas liver.
D. Pituitary gland 11. A. The pancreas is both endocrine (secreting
insulin) and exocrine (secreting digestive en-
18. Which organ helps to maintain electrolyte zymes) in function.
levels by controlling excretion? 12. D. Only the collecting duct is not a component
A. Colon of the nephron.
B. Liver 13. C. Acetylcholine is the neurotransmitter in the
C. Kidney axon terminal of the neuromuscular junction.
D. Heart Estrogen and substance P are hormones. GABA
is a neurotransmitter, but it is mostly localized
19. Which of these organs is the largest visceral to the brain.
organ? 14. B. Estrogen is a main female hormone and is
secreted by the ovarian follicle. Testosterone
A. Colon is the primary male hormone.
B. Liver 15. A. The frontal lobe of the brain is respon-
C. Kidney sible for higher integration, planning, and
D. Heart thinking.
16. C. The pulmonary alveoli are the smallest air-
20. Which of these cellular organelles is the main filled part of the lung and are the site of gas
difference between prokaryotic and eukary-
exchange between the lungs and the blood.
otic cells?
17. D. The pituitary gland releases hormones that
A. Mitochondria stimulate the other ductlessglands and has
B. Cytoplasm been called the master gland.
C. Nuclear membrane 18. C. The kidney maintains normal electrolyte lev-
D. Endoplasmic reticulum els by controlling excretion and reabsorption.
The APhA Complete Review for the Foreign Pharmacy Graduate Equivalency Examination®

19. B. The liver is the largest visceral organ and is Moore K, Dalley A. Clinically Oriented Anatomy.
important in detoxifying the blood of pathogens 4th ed. Baltimore: Lippincott Williams & Wilkins;
and toxins. 1992.
20. C. Prokaryotic cells lack a nuclear membrane. Schottelius B, Schottelius D. Textbook of Physiology.
In eukaryotic cells, the nuclear materials 18th ed. Saint Louis, Mo.: C. V. Mosby; 1978.
are located within a nuclear double-walled Shier D, Butler J, Lewis R. Hole's Essentials of Human
membrane. Anatomy and Physiology. Boston: McGraw-Hill;
2000.
Van De Graaff K, Fox S. Human Anatomy and
Physiology. 4th ed. Dubuque, Iowa: Wm. C.
1..17 References
G Brown; 1995.
Vander A, Sherman], Luciano D. Human Physiology:·
Drake, R, Vogl R, Mitchell, A. Gray's Anatomy for The Mechanisms of Body Function. 8th ed. Boston:
Students. Philadelphia: Elsevier; 2005. McGraw-Hill; 2001.

\
athol g and
athophysiol gy
Joseph Presley, PharmD

2"'1. Basic Principles and In normal states, the capillaries and venules allow
the passage of only small molecules out of the vascu-
Mechanisms of Disease lature into the surrounding tissue, retaining macro-
molecules, such as cells and plasma proteins, inside
Inflammation and Repair the vessel.
Inflammation is the reaction of vascularized tissue in In acute inflammation, the endothelial lining of the
the body to local injury or insult. It is a protective at- microvasculature is altered, thus allowing increased
tempt by the body's defense mechanism to remove the permeability of macromolecules into the tissue space.
harmful stimuli and return the tissue to its normal With this increased vessel permeability to macro-
structure or function. molecules, there is also movement of body fluid, which
Inflammation can be caused by numerous injuri- causes swelling or edema at the area of injury.
ous stimuli, including the following:
IJl Chemical irritants or toxins Cellular component
lKl Mechanical or physical trauma Along with vasculature changes that occur during
l¥.ii Altered or damaged cells the inflammatory process, numerous cellular changes
Microorganisms are also taking place. As fluid is lost into the tissue
space, large amounts of red blood cells, white blood
Clinical signs and symptoms of acute inflammation cells, and platelets remain behind, causing blood vis-
include the following: / cosity to increase.
~ Redness This increase in viscosity causes a phenomenon
JliJ Fever called margination. Margination is a process in which
Swelling white blood cells, or leukocytes, relocate from their
Wl Pain normal central location in the bloodstream to the
periphery along the endothelium wall.
The inflammatory response that is produced by the After margination progresses, leukocytes eventually
body involves two distinct components: vascular and adhere to the endothelium lining before emigrating
cellular. from the blood to the tissue, where they are responsi-
ble for limiting the harmful stimuli and beginning the
process of repair.
Vascular component
The vascular component of the inflammatory process
Mediators of inflammation
begins with the initial injury. Following injury, the
body increases blood flow to the site through dilation Histamine is stored in the granular tissue of mast
of the arterioles. Dilation of the arterioles, in turn, ulti- cells. Once released, histamine produces vasodilation
mately leads to dilation of the capillaries and venules. and increased vascular permeability.
The APhA Complete Review for the Foreign Pharmacy Graduate Equivalency Examination®

Hageman factor is stored in an inactive form in Edema


plasma. Once activated, this plasma protein triggers
Edema is the abnormal accumulation of fluids in
the activation of four different cascades or systems
the interstitial spaces of cells or tissues. To under-
important to inflammation and repair:
stand edema, one must understand the distribution
m The coagulation cascade leads to thrombin for- of water between the body's fluid compartments. In
mation, which converts fibrinogen into fibrin, the normal adult, approximately 50-60% of lean
ultimately leading to clot formation. body weight is composed of water stored in two
fill The kinin cascade leads to the production of basic compartments:
bradykinin. Bradykinin is a peptide that causes
vascular dilation and increases permeability. Ell The intracellular compartment contains approxi-
The fibrinolytic cascade involves the conversion mately two-thirds of total body water.
of plasminogen into the active protease plasmin. WJ The extracellular compartment stores the remain-
Plasmin has two important functions: degradation ing one-third of total body water.
of fibrin clots and activation of the complement The extracellular compartment is further divided into
cascade. the interstitial space and plasma space, which are sep-
iiil The complement cascade has many important arated by the capillary wall.
functions. It produces proteins that form the Normal exchange of body water from each com-
membrane attack complex, which attack harmful partment is controlled by hydrostatic and osmotic
microorganisms. Additional activated proteins in pressure, which is regulated by plasma proteins. Dis-
this cascade are mediators of inflammation caus- ruption of this normal exchange explains the etiol-
ing vasodilation, increasing vascular permeabil- ogy of edema.
ity, promoting chemotaxis and phagocytosis, and Causes of edema include the following:
initiating histamine release.
Ill! Increased hydrostatic pressure
Arachidonic acid is a fatty acid found in many cell !ll! Decreased osmotic pressure
membranes. Two different pathways metabolize Ill! Increased vascular permeability caused by
arachidonic acid, which produces potent inflamma- inflammation
tory mediators. . Ill! Obstruction of lymphatic channel
Prostaglandins and thromboxanes are produced Ill! Sodium retention
from arachidonic acid through the cyclooxygenase
pathway. Prostaglandins induce vasodilation and
increase vascular permeability. Thromboxanes facil- Congestion and hyperemia
itate platelet aggregation, which is important to the Congestion and hyperemia are increases in blood vol-
healing and repair process.
ume in a given tissue or vessel.
The lipoxygenase pathway results in the produc-
Hyperemia is an active process in which blood
tion of leukotrienes. Leukotri9.nes initiate chemotactic
flow is increased to a given area. An example of this
activities for white blood cells, cause vasodilation,
process can be seen in acute inflammation.
and increase vascular permeability.
Congestion is a passive process in which the
drainage of blood from a given area is interrupted.
Hemodynamic Disturbances An example of congestion can be seen in valvular
stenosis. In this disorder, blood volume is increased
Hemodynamics is defined as the function of blood
in the cardiac chamber preceding the valve that is
flow or circulation and the forces involved. Alterations
failing to open properly. The process of congestion
or disturbances in the normal pattern of blood flow
may become a chronic condition leading to permanent
can be harmful to the organs and tissues of the body.
damage of the affected tissue. Varicose veins are an
Examples of disturbances in circulation include the
example of chronic congestion.
following:
m Edema
rx1 Congestion and hyperemia
Hemorrhage
li'l Hemorrhage Hemorrhage is the loss or escape of blood from the
t%1 Thrombosis circulatory system. Accumulation of this lost blood
E1 Embolism may be external or enclosed within the tissue space
E'l Infarction of the body. A hematoma is referred to as the accu-
~TI Shock mulation of blood within the tissues, and can range
Pathology and Pathophysiology ·

in severity from mild (e.g., a bruise) to more severe arteries and causing severe obstruction. This condi-
(e.g., a subdural hematoma). tion is known as a pulmonary thromboembolism.
Petechiae are pinpoint hemorrhages (<0.3 em) Emboli can also be found in the arterial system,
seen most commonly on dermal or mucosal areas. most commonly originating from the chambers on
Purpuras are widespread hemorrhages slightly larger the left side of the heart. Cardiac abnormalities, such
(0.3-1 em) than petechiae and usually found under as atrial fibrillation, increase the risk of embolism.
the dermal surface. Ecchymoses are larger (;:::1 em),
often blotchy hemorrhages that are also found on
mucosal or dermal areas.
Infarction
Hemorrhages can be caused by trauma, vascular Infarction is the process of forming an ischemic necro-
wall damage resulting from disease, or malfunction sis within a tissue or organ. Ischemia is a lack of ad-
of the body's normal mechanism to maintain hemo- equate blood supply to an area of tissue. Persistent
stasis such as clotting. Systemically, the significance ischemia can result in necrosis (morphological changes
of hemorrhages depends on the site, rate, and volume indicative of cell death) in that area.
of blood loss. The etiology of infarction is most commonly asso-
ciated with thrombus formation in the cardiovascu-
lar system, leading to various vascular diseases.
Thrombosis
Atherosclerosis is an example of a vascular disease
Thrombosis is the pathologic process of formation of leading to infarction. Atherosclerosis is characterized
a blood clot within the circulatory system. The formed by thickening of the arterial wall by lipid plaques. Old
clot is referred to as a thrombus. plaques eventually calcify, thereby narrowing the
Thrombus formation results from three factors lumen of the artery, favoring thrombus formation on
known as Virchow's triad: the plaque surface obstructing normal blood flow.
m Decreased blood flow
Injury or abnormality of the endothelial wall of Shock
the vessel
N!1 Changes to the normal properties or processes of Shock is a serious condition involving decreased per-
blood coagulation fusion of tissues and organs because of inadequate
blood flow. Signs and symptoms of shock can in-
Thrombi can form in either the venous or the arterial clude cold, mottled skin; mental status changes; and
portion of the circulatory system. Because of high pres- oliguria.
sures on the arterial side of the system, most thrombi The etiology of shock can be divided into four
are formed by an abnormality of the vessel wall (e.g., basic groups:
atherosclerosis). However, on the venous side, blood
flow is of lower pressure, and most thrombi there are lliil .Hypovolemic shock is due to inadequate circulat-
formed because of decreased blood flow. ing blood volume most commonly caused by
The effect of throm\ms formation can vary de- hemorrhage or trauma. In hypovolemic shock,
pending on the site and htent of occlusion. Thrombi cardiac output (CO) is reduced because of de-
may eventually be broken down by fibrinolysis, caus- creased venous return, and systemic vascular re-
ing little harm; they can propagate and cause vessel sistance (SVR) is high because of compensatory
occlusion, which leads to tissue damage or death; or vasoconstriction.
they can embolize and move elsewhere in the circu- llil Distributive shock is also due to an inadequate
latory system. circulating blood volume; however, fluid is not
actually leaving the body as is seen in hypovolemic
shock. Infections (septic shock), anaphylaxis
Embolism (anaphylactic shock), and medications (neuro-
An embolism is the transportation of a detached genic shock) are common causes of circulatory
mass from one area of the bloodstream to another. vasodilation leading to this type of shock. CO is
Most emboli are formed from blood clots and are usually normal to elevated, and SVR is reduced
referred to as thromboemboli. in distributive shock.
Most commonly, thromboemboli are formed !lil Cardiogenic shock is due to cardiac malfunction
within the deep veins of the lower extremities. They and is most commonly seen in patients suffering
eventually become dislodged and flow through the myocardial infarction or cardiac arrhythmias.
right side of the heart, terminating in the pulmonary CO is reduced, and SVR is increased.
The APhA Complete Review tor the Foreign Pharmacy Graduate Equivalency Examination®

B1! Obstructive shock occurs when normal blood Numerical abnormalities involve defects caused by
flow is interrupted or obstructed. Pulmonary missing or extra chromosomes (aneuploidy). Aneu-
embolisms and cardiac tamponade are examples ploidy has multiple causes; however, it is most com-
of this type of shock. CO is reduced, and SVR monly caused by nondisjunction during the process
is increased. of mitosis. Down syndrome (trisomy 21) is the most
common numerical abnormality; in Down syndrome,
The goal of therapy in patients with shock is to restore
blood flow to organs and tissues until the underlying three copies of chromosome 21 are present.
cause can be corrected. Structural abnormalities involve missing or ad-
Shock can potentially progress through three stages: ditional genetic material attributable to deletions,
translocations, inversions, and duplications of chro-
Nonprogressive stage. Reflex neurohumoral mosomal segments. The Philadelphia chromosome
mechanisms are activated, and normal circula- seen in some patients with chronic myelogenous leu-
tion is restored. kemia is an example of a structural chromosomal de-
Progressive stage. Tissue and organs remain hypo- fect. In this defect, translocation of chromosomes 9
perfused, thereby increasing damage and decreas- and 22 occur.
ing the likelihood of compensation. This condition
can be seen in cases with severe blood loss.
Irreversible stage. This stage occurs when the Abnormalities caused by environmental factors
body has sustained injuries beyond repair by Exposure of the developing fetus to environmental
therapeutic intervention. agents or substances, often called teratogens, may
cause developmental defects. The exact mechanism
Developmental Defects by which teratogens cause harm to the developing
fetus in most cases is unknown. Teratogens may in-
Developmental defects are defined as those originat- clude drugs, chemical agents, infectious processes,
ing in the embryonic period. Most developmental de- radiation, and maternal disease states.
fects are discovered at birth; however, they can affect Many drugs, including alcohol, and chemical agents
an individual at any point in the life cycle, from birth are well-known teratogens causing a wide variety
to adulthood. of effects. Retinoic acid is an example of a teratogenic
The etiology of developmental defects falls within drug; it causes craniofacial deformities, cardiovascular
four general categories: anomalies, and neural tube defects.
The result of genetic or chromosomal abnormali- Microorganisms that are present in the mother are
ties (intrinsic) often capable of crossing the placental membrane and
The result of an environmental agent (extrinsic) subsequently infecting the fetus. Rubella, herpes sim-
f'il Multifactorial reasons (intrinsic and extrinsic) plex virus, varicella, and human immunodeficiency
Unknown or unidentifiable origin (idiopathic) virus are a few examples of infectious teratogens.
Radiation exposure during pregnancy may cause
Developmental defe<Js can be divided into four sig- growth and mental retardation, as well as other de-
nificant subtypes: velopmental defects.
Malformations are defects in normal development Maternal disease processes, such as poorly con-
as a result of an abnormality of intrinsic cause. trolled diabetes mellitus and hypertension, are known
t=~ Deformations are defects in the form, shape, or to cause deformities such as limb abnormalities and
position of a body part resulting from abnormal congenital heart defects.
mechanical forces placed on the fetus during Critical factors affecting teratogenicity include the
period of development when exposure occurs, the \
development.
Dysplasias refer to defects attributable to an abnor- dosage and duration of exposure to the teratogen, and
mality in the cellular organization or arrangement. the genetic makeup of the exposed subject. Exposure
Disruptions are abnormalities of normal growth of the embryo to a teratogen during the period of tis-
and development caused by extrinsic exposures. sue and organ formation increases the likelihood of
major congenital anomalies.
Both the dosage and duration of exposure to a
Genetic and chromosomal abnormalities
given teratogen are important; however, not all te-
Defects of genetic origin can be classified as numerical ratogens exhibit similar dose-response relationships.
or structural. A single exposure to a very large dose may be more
Pathology and Pathophysiology

harmful than multiple exposures to a lower dose of point where pass~g~.~-annot..oc<;:ur. \Yh~}l th~ ~1IlP9lL
the same teratogen. become lodged, tumor growth resumes un~iUIJY.~_s_i_Qil_
oTthe-surro~~ding t1ssue-oCctirs;_-th~~~- the tull1QI.
ga1ns:~-cc~~s~f9:a-secongary sjt~_. . ' .
Neoplasia --f,§~ l~U!1. is one of the more common sites of sec-
( Neoplasials the .2vergro}Y!h-or abnormal pr_olikr:;:!~ onoary tU~<;JfS spread through the bloodstream. This
·tfonof cells of a tis§ue. A neoplasm, also known as a coiiJition is most often seen with malignant tumors
tumo_f, is ari~bn~mal mass of tissue attributable to at sit~,of gopqsystergicveno_tis_&~ain.:<I,ge, such as the
uncontrolled celltila~ prolifer_?:ti_s>g. -~!~~~!r, pr2.~\~.te~ br~!~t-~-t and c~g.
Related definitions ftLqfg~gLa~~!JJ~. .
Many similarities between neoplasms and other distur- Research into the cause of neoplastic growth sug-
bances of growth exist, making terminology difficult. gests that alterations, or somaticmu~~!ions, in DNA
The following are terms used in growth disturbances: (deoxyri bailliCie1c'ac1d) ··~'lqtreilce'By'·Efl'rcinogens
ultimately result in the disruption of normal cell pro- .
!lil Agenesis. Failu~_of -•
;:7"!J-
organ
-
formation
•- -.. _
during
- "
_ .. ~~r=-~-· ~~•·
liferation and death. Carcinog~nsarephysical or chem- ,
em6ryo development. 12a'f'ii~ilts capabTe oCcausing genetic mutations.
!lil Aplasia. Failure of organ or tissue development. Examples of known carcinogens are as follows:
llil Hypertropjy.,. Enlaf.g~m~ntor~;ergrowth of~n
~. Tobacco and tobacco smoke
·~or tissue because of an increase in eel~
llil Hyperpkz!;iq... ~nlargement in the size of an-organ
ll':l Radiation (e.g., ultraviolet rays from the sun)
;.::-...;;,..~."";":,_,..-_..-=>"'~·':::~-'1-..<L,;t.
ll':l Viruses (e.g., human papillomavirus) /
- ''orf15sue because of cellu1~~1-<ilii<%~t.JJ?Jl~r-
Asbestos
!!il Atrof!_f!2!.. Breakdo\\'!Coi:"'aecrease in size_of a give~
Eody tissue or organ. . .. . . . Certain pesticides
~ Certain heavy metals (e.g., l~ad)
!lil ~BfJgiUl;-~Y in <:el.l WJ?~_, usually caused
·by an adverse stimulus. As previously indicated, the formation of neoplasms
!ill Dysplasi~:.·i\f,r{;r;;;fity in the maturation ordif- involves mutation.s i? th~ ~~A~t_~ryg~J?:t:~ COJW9lli.vg_~_
fereiit1atl.o'n 6£ cells within a tissue. · ·. - cel~2~~h2&d e!~~!!~~~gn, such as pr()!()-_()ntng~n~~1 ,
tunioi:"suppre1sor_geQ~.§, genes that regulate cell death,
Characteristics of neoplastic cells ana DNA-~~~r~,g~nes.
.....~~~.;;._>!J-i:J::..;.:J!i;:~~
Two types of neoplasms exist-benign :;md malig-
nant----:-which differ in their groWtli pahern and 'Proto=oncagene?
beliavi'o-ls. .,~~~-"""''"""""'"'~'·-·· Proto-oncogenes are genes withm~!iJl~JHRS!i9l\fu-
---Bentgn~eoplasms characteristically are slower- most importantly coding for proteinsthat control celT
growing tumors thai tend-Il.ot-ta-·1nvade-~urrol.li.iding" proliferation, differentiation, and elimination. Defec-
tissue. Benign tumors do not have the ability to spread tive or mutated forms of proto-oncogenes are called
to-other sites ofthe body. .. oncogenes. Oncogenes may result in the uncontrolled
Malignant neoplasms grow more rapidlyth<ln their production of growth factors, ultimately leading to
benign counterparts, often invading surrounding rapid and unnecessary cell growth.
tissue and c~using disruption of normal fun~tion.. Several mechanisms exist for the transformation
Malignant tumors have the ability to metastasize, of proto-oncogenes into oncogenes:
~~~~_cl_i~E_t?~1l()ther site within the body .and for111- (I' m. Point mutaticm. A single J:l!ldeotide change in the
mg a secon~:l!Y tumor. .. DNA sequence thatre~ult~-Gi.-achc{nge in a s!p.gl.e
amhio acid in a prot~i_p (see Chapter 5).
Metastasis lliil Gene amplification. Overexpression of the
Some malignant tumors possess the ability to spread to enc9ged protein. ... · .. . - .
distant sites of the body, usually thr~~h l!!Y.~~i9JL9i l=~ i\l! Chromosomal translocation. In;:tppr()pri;:tJ~
_t_~~--~19.s>~_s!~~~~or lXE~;,~~-~.!~~-~~l~!e~.~y the growing expf~SS.~9n of th~.g~J:l~: . ·
tumor. Once entry into the blood or lymph is gained, .. --
~----------~--····--·--·-···--- .....

tumor growth continues, eventually sepa_rating into.. 1 Tumor suppressor gene§_;


smaJfeinboli. ' . Tumor suppressor genes are r_t;_~()psiblefor inhibit~
- -Tiie~~3JJ~!?glLar,~.thtn.s~r!:i~cLalm1g :with.~th.e_ ing cell growth, division, and deat_h. Mutation~£
normal. floyv:
--~---~" --
of bJgQQ...Qr lymph u11til they reac:h
'""'- --··---·
~
a 'tumor'sil'ppressor
-----
··--,~--~·- -
··--·-""
.genes- result in' a loss of function, ~~~.m~~
The APhA Complete Review tor the Foreign Pharmacy Graduate Equivalency Examination®

thereby causing the cell t()___ig!.!.QIT_1J9lr!H~1 iqh!b.i~QJY_ (d,i~~£2li~J Hypertension is classified as£El!!l:!~ (also
!ig_~~k:____ ~---- ·- called e~f{t!Jlqll or ~e££U~~: ------~
Tumor suppressor genes are !~essiv~ !ll~anA11:g
f.'!.i!!!:E!Yh.J!Pt!.rtfl11§i.Qn is a much m()r~ s;_9m11L~
_b_()!? JJ_Or!Tl<ll;:tllelt:_s _must !!!_~!_<!t,e.?~!C>E~-~E:~~~~E~!Le_,~!c. C()_Q.d~_!~qn in which no spedfic~ca\}Se Gan.be i<fs:U:_
growth ca1l_()_ccur. ·
. ~·-- .. ---~- ---~~----·~---~.;,,-,- _,,;_,;:;;:o:-·~-;"--"--
_
df~e-~. ~l'2!9~ill1.<lte.ly 9Q::-2.SJ::o of hypertensiYe_

~~~~
cases are considered primary hypertension,_
l:li! Seconcjqry hypertension is a di~~r4~T in which th~­
_bl!f}:P_to~j~)s The normal process 2(RE9.gE~?1!P~e~.E~JL causel.s kno"'n. Renal artery stepo~is., chronic
~-e:_~!~ resulting in_~!im_iQ_9-JiQJlOf cells from an orgail-
iSJ1_1;. Qenes regulating ap()pt<?~~~- are responsible for
re;;~T_di~eas~;and hyper~id~s,\~£9,nism e1re_a f~YL
exafi1ples of causes of secol}dgry hyperteilsion. _
promoti11g and inhi~iti{lg this normal process. Muta-
donof this gene type J,TI-ay result in the failure of cells The maintenance of blood press:qre depen9s on ty,ro
to die, thus causing accumulation .
.•... , ;- -~ .:..' :_'. A"'-~·-cp;,;,:,."'., --'-"-· ---~!, · ~-,T•- ~''"'" "'""',._'~'~" · · ·· . -_.:::-;·,';.-=·.;~4;:t::-~>.-"f:'; >7~
fact{;is: cardiacou!,put <md ~Y~£~!l:'l!EY.9-§.£111~r rt=.s.ls_!_-_
ance_, Alterations increasjng .one or bo!h.of these
DNA repair genes factors may lead to hyperten~>IQ.~.-------- -
DNA repair genes are responsible for CQl.I~£ti!JggtQ~"~­ Mos~ ~g_I):l.!!l911IT.,. hypertension is caused by ip_::
that may occur during cell duplication~--------
--~--0 •--. , "*='•c• ,,-_,_,..-~'-'>-': •>v~• __ -._.- ..• - • ,.:; ''jL:';fJ•• ••·"·" ~· ~,1·. f•''• ;":\-.-~ ';•_:.~;-:_:;
creases in §X,B,. Resistance is.increased by areducti()l!_
1n ~e~s.el size (vasoconstriction) or irr~:ceas_es in blood
Effects of neoplasms./· viscqsity or volume.. CO is increased by conditions
1&£?-~it~S.l,~ oftut11Qrs on their host are often rela!e£~o affec~ing ~~-~!1I'il-}f_or ~!I<:>~e vol,l1m~·
tqe_~i~~ and loc;~tigg.Qf.the tumor and can cause ~i~S.UJ-':.­ Discussed next are a few factors that may affect
destrw::tiQJ1.and obstruction. Destruction and obstruc;: __ CO or SVR, thereby causing-<.•<-- hypertension .
.tion can occur with be~ig;-and malignant tumors.
"j\:-~.<h">"'~'·"' ,,,,,_ .. ~,,. ,....,. . . ' ..... ·.~-- ''·' ~

Syste111f effec;ts oft~~~rs~y-be (Ja't~dt~ abnof-


mal hormbne production, nutnt!Qn(ll deficiencies, and
Abnormalities of the renin-angiotensin sy~!~l'll..
·'" ··- (l ... -·". " < - < _.,

infectftm. Hormonal effects produced by neoplasms Almorn1~Utie~ of the r~pin~_a~J?.,Zi()t~J:l~!n syste,m can
in endo~~ine glands m(ly be life threateJ:ling. For exam- result in hypertension_._Re,nin_is secret~d. by~h~iu:lCta-
ple, overp_roq_u.-s;t.i9n of in~y!insaused by an.a.d.~gm::t
()f t~~ii1ls;reas, may result in ~!ll!gLhxBg!sf;lJ.~w.i,a.or r~i~::~;~~r,;;~~j~~~ i~:~;_F~~Til~~~
~rlt~lz,c~mia. . ·- is responsible for c?.~\Tertil}g ~~sl2!~~~ to_
· ·· ....·""~fl1-~t912ID£c:%L~sti&J~J1C:i~,~~. _such as a11~.111i~, often angiote,11~!n.!. , - · ---
occur in .~~~ll-~~R~i~· A_ge@:l<::<ln occur through . Angiotell?in I is then converted to a~gJc.?.!.C::Q~jn:JL
111<l!lY.mecharusmS.. 'Directly, anemia m_~_y])~_ C(lUsed. by an enzyme called angiotensin:-c;_gnv.grtf1Jg~?.?JZYme
by J:,l~~_gigg C<l;_l!_§.~~- by the igy:Cls.iY~!l~§. ofthe tumor,,__ (Ai.=ID. Angiotet,l~l:l II, ~ potent.directvas&ons~1Ct21}·
oili?,<:>~YJi§~Ues_C}p.d y<:;ss~l?.::Metasta tic tumor. grq.wth also stimulates tne r.~lease of aldosteJ:QP.e (responsible
can als.9 invade_bonemarrow, thereby causing a S.:t:lP..:::. for sodiu~ a~d water retenti~~). R~t~J:1ti<:>11 of s_od~UJ!L
pr~_ssion '()f~~r~_ii[~l}:ctiqn~- and water incr:~ases pl<;>qci,:y:q_!urne,, thereby incre~lsipg
Cachexia is a wasting syndrome resulting in loss vascuEir resistance.' .. . ...
of~C:>ill:I:itciiid l~.a~l} bod:y:.ma,ss~, It often occurs with,
1 ··sy~path~tic nerv~G~·system
malignant neoplasms, Cachexia results in a g~.!l~.t:al~
ized wealznes_s, weight loss, anor,e,~j_a, and fe\rer for
the tumor host. .. - ·-~ The__~Y,U12~lh~tic neryq_us system is il11P9ftq_J1J in the \
regulat1on-ofrwrl11alblood pressure. This process of
blood pressure reg~i~ti~n iscontrolied through stim-
ulation of adrenergic. receptors (alpha and. beta) by
2.. 2m Pathophysiology of Disease cate~hola-mtnes,: ,1D)~,.£!l~mrJ2~.!lS~S~f the, _syffipa,thbti~c
States Amenable to nervous system m:iy cause hyperte,nsion~ - -,c- ~' --- -< • >' l __ , ,•. ,__ , .. _-, .·-- • ... , ~·~-~~- ~~

Pharmacist Intervention ,, .. -·----.....--~-·~-~-· ·~...-----"«--~.,p·-·;,.,_·~~.,

(Natriuretic hormone -"


'~~-~~--f·"•">.·.--~-....~=-•'"''""~··'-,.,r_';•~.<J.A
Hypertension .Atrial !1;_?-triuretic 1?,~21!4~ (ANP) is secreted by the
Hypertension, a leading cause of death in the United <!ttia. g_Ci:Jii .heart._ in resp()n~~__tg i]]c.;:r~_CJ,~e_g_IJJoQs!
States, is defined as a repeatedly elevated blood pres- flo~.• 1\NP iJ:l<;~~<lses usjn.~rx_ f(,JC9;~ti9lLQt§Qdi~IJl..<ll)~
sure exceeding 140 mrnl-Ig (systolic) ,;.-,.
90 mmHg
or "'""'" ,..,.__..,," -· -· , -t-·=- .~-;o'_-_ ,~.-- - " · ....,;;.,"-~~'"""',-c;,_c· ----ft~" "-<•~-.·=--,_,., .•..~.
~ater1 thereby causing; <1 dec_r_t:"!.s.t:_iP: glg~e>_2,£E~~s~_E-~·
Pathology and Pathophysiology

In addition to its renal effects, A.l~IE.i§~ill~i.Q.!ho.ught_ Symptoms of diabetes mellitus may include polyuria,
_to <:!f~cty_~scl1t<lrsmo.oth~ byjnhibiting tp~ polydipsia, polyphagia, fatigue, and weigh~
- .. •''·"
s'odi up,:}?2l,am~§.iEm.Aitfl,§~J>JJ,UW,· Thi~ inhil?itiog
-~=- :--~,__,,_ -·=od~~i;{;<·,~u·• .,' --

increases the intracellular concentration~ Q£ ~o<ii.um Type 1


·ancf~~icium, thus ind~~ing~~socopstr·i~tion, ····-··
~--~-·.,...... -~~t~~f:Y~JJ~-5~~~;;::,_:,;:_:;-.,:;rr1~...::f.'~-;.-,;""'
Patients with ty£~L~.i~~~!,~~"~IJ::;~.~l,i!2,~-_!;.a ve Jl..J2~Hne::
......•...

(Endatllelial gy~fuD_9i;;r; nent loss ()f.[n~.l1Jinl't:941J~iion. TyJl.~1~~~9.':1!1:!.sJ_g£.


·
,,,,- ->-<- -----··J=--~_,,:..;-=o:--;--·,•·:c ,. ' .•.-. -·---
approximately 10% of prirnat:Y.. ca~~S_()f dia.p~}~~-
Numerous vasoactive subst:1nc:es are Qrgducedjn the "--~"· menltus.. ·· ·
··vascular.eliS!9t1ic;Il!lffi~-Any.dysfunction oUb.e ~in­ J~J"'Q,§l..ir~~s. Qf. type l.result from an. ip;l.fl!:l]JW~
·aotlielli7'~-;n~:yTeadto alter~tion of vascular ton~, media.t~Aciestru~tion of bet.a..<::~Us of the.Panc:.t~::lsJJy .
··P'~'t~;{1I;fiy causing h~r~!!.~!t~t.2i. ·_I~lym£h2~X!~§JiYJ2~rgly_~emia res-~lts, caused by an . ··-· .
f'Jf:l ..]'lilii~·g}fi{]e is a potent vasodilator released by iilsulm deficiency. The rer.1aini11g cases are idiopathic
the endothelial cells in respome t.o. changes in. blggd' rn riatuie,~ 6ec;use·;~to1~m}iDitris not ;~IJe;t"~in..
-p-ressure. It has be.en suggested that ()xid<l.Y.Y.t;..s!rt;~s
- ••......_,..,,.,.. -··-•·••••--~-~--~ • .------·~···

m::tL<::a us~ ~-~-~D£t~g~y_ i~"'t1~!fAE-H~ifl.'~ thus causing .


liynertensiQ)l.
" - · - ' ',.<~;£-oc<f.'tz,·.~"?i> ~ ,..,.-__ ,,-"'.fo~--=,=~''-~"1v:,• ~%'f/u-d•"'>1,

t~if~i~~i· ~e~e~;ch su~gest~ ~·~at ~oth .~~l:~~i£~a.rd


,ff,~d.·,;_;g,~ .. ,,c.,,,,,,;>,:,_;;_-,. environmental factors are responsible fortriggeriJJ$
~··" EndotheJial cells .also release a Y:;Jo.~Q£Q!1§lt;ic;:,t,i!W;,. a~t9L~m~!i~::il~§:t~~~tipn . .9n:s,et . q£ .9i§~.i-se ..o~s~~:§
substance called endo~helin. Numerous vasoc;:on-, m<;}~l.~f.QU11l1QUly_ in .,c9,ilci~.¥.Q;.,,.ang_ .adqk§<::~!J.l~,,,.,al­
strictin.g'ageg!s, s~~h~~:iailR"te,B§i~Jb. Yof1§,<;>J;if~i~mL .though OC:£11-~~iQ!;l.a.llY.Ih~.disea~e may not be Pf~~§£1.P.t .
andJ];~~~,PA!}.~l?~f,i.~<c) hive been suggested to increaae
the refease of~llciSlthd~n. Overstimul?:tion of the pro- ur:~iL.~~ij1,~~~£9.:. ·
duction-of e;;J~'th.eiin may cause hypertension. ' .
· " _ • · .. _-
'~" ·~'-----:.'· ,~,-~~ "'._,..,,,·_·--i-· ;: .,-w,_~-~-·~.;o-;-;c';-~f:;;:;.
Type 2
Diabetes Mellitus Type 2 diabetes mellitus involves a combination of a
relatiye_;t;~~~.§.tenceJo..the aEtion o£jpsulinancl a ddi~.
Diabetes mellitus is an endocrine disease in which dencyinits se,cEe.~ign. Type 2 accounts for,approxi-
the body does not properly produce· or__!!;§~jfii~1!n,:~ mately ..9Q,%,,o£DJ:imary caS,es..
,re,~l11~i~~J~j~\,~X£~rs!Ys~mLa,,:*.... ----·---~ ··- Although t~e-~p~cific cause.of type 2 diabetes mel-
·--··Insulin_~§ necessary for the transport.. <:>LgL':l.~()~~
litu-s!~ nptkt;to\Yn, research does show that it isJ2?!s
into cells,
where it is stor~q JlS glxcog~fl tobe usecljq_r
j~l!HU1~,m~4iat~fi. Type 2J~.~ ge_g~t,i~cUseas~_; how-
eiie-rgi"'In normal p~ys!qJqgy~-st-~tes, insulin is pro-
ever, environmental factors are belie;yed to pl~y an,
"cfucedby the beta -cells of the islets of Langer hans qf
important Eart in its onset- ~n? p~£P.~!:gg~-~2f1·
-the pancreas. Ins~lin ~elease is adjusted in.. t;e.~pQ.J.l§.~ "' .. '' ... ;__ . ___ <o---·--'"~--~ ~ -·····-.'.:'~-'- ,·~---

to serum glucose"fevels:.%E••V•·><% .;;:·"""·"-··"··''"··~-~·,.D.>.. -•·•••·•"


... _,,-, ,.,._,, __ ~ • ,, .•, _, -:-·-~,;:_-,_n:c'\!~"r'.,:;.:;:..,,.--£i;;:;;•·~---

' Iri' addition to glw;:ose l].pJ;:tlz('!, if1SUJif.l.stimulates Complications of diabetes mellitus


gmi!!9 _q_c;icil!Ptake and, thus, pr~tein synthesis by Acute
muscle. It cim also stimulate fatty acid storage in Previously mentioned symptoms o.fpoly~a, polydi£::_
··adipose ti.s~l1.e~-- , - - · ·--· · sia, and_£C?Jyphagia are all ~a result ofhYR~.rglyc:em5l!
· '"blabetes mellitus is classified into two primary ··and may be seen in__~s>,!~~---!IP,~.l-~?-dtyp~~±",R9ximts.
types and two secondary types; however, only the Po!Y!:!!:!.~pccurs when the tl1p~s]gJ.clJ.2E..g1l1S9S,~ E~;",
_primary typ~s will be discussed in detail. The pri- abs9.fE!,t9nJJJ'Jh~~kigneys 'Iiasb~en e:¥q~eded_. This
mary types are \l.S follows; condition results in qsmo.tic:.dil1f~§is, which increases /
(i Type 1 (formerly known as insulin-dependent di- uriii~"oufput (eoly~~i~) .~x;·;;~~-ft "o£ this increcis~ ill
abetes mellitus) -r'[)Dr-'1 url'ne""oiii::i)u.t, .dehydrati.on ..oc:.~urs, which.stimulates "
~Type 2 (formerly known as insulin-independent thirst (polydipsjq). Il}f!ea,s,~d }nm.ger (po_ly_P,~gg[ql !'11::1Y
diabetes mellitus) I~ ..~~ r-"'., be_a !~Rltof significant calmi~.)oss'when glucose is·
T~st1~:ili~:.Urilli~"~-,~- ,_, ... -- ..
Secondary types are as follows: -·---ij)qlz~tic k?toacfc{o§i~.(DKA) is a yotentially lif~~
'-~, Gestational diabetes thr~ea.t:~~i~g ~?P~:n~-~1:igg. !J occurs more tre-9u~~ -
.!'§ Other specific secondary typ~s, including_clmg;: .R~!lts wii:h ..rrp.!l_~i§..f~~~- DKA occurs when severe
indu-cec! types. thoserelatedto l?enetic defe~!s and beta-cell destruction has occurred without supplemen-
· .2Itli~J>et~;c~U,.geneti.s ..4.~f~~,t.,s,,Lr:. ig_~-~!i!l~~S~L?PL. t~!{~p__o(e.Ji:(:)g~-~9~~J!l§~H~~t!ler~£Y'.Ii1-i:he.absencec;f
f~~~f~;E;:u1sre~.§,flL§~~§,C(,_~ndoc:ino 12 ::t.thies,
~:;. =----~_-·_;_,:,--,·:.Tt'd. ,,__ ->; - -·--
ana adequate insulin_th_erapy and aq_ig<;:~~~_s.~)!l:.S:9QI1t~r-..
regulatory hQEW9!1e.~ glucose Ievels_begi11to increas~~=
.!0.·.-.· ,.:,;__·; -;. ····-~--- •. ·--- __ ., ___ .•. -.---···-
,;· The APhA Complete Review tor the Foreign Pharmacy Graduate Equivalency Examination®

Despite this increase, the nece&sarx uptak:e of glucg~e !il High-den§i!JI.Jipnpmte.ins (HDLs) areoften re-
cannot oc~lJX-iD. ml!§fJ~ Ji§_~ii~;J<}Jc) ·0~ the]lv.er bec<lu~e. f~rre<!_t;;as "~s~£SL.~h9l~~~.t;QL~' HDL~-;re,.§.~:=­
of the lack of insulin. As a resiJ"it of this lac'k·-~-f neces- cre~ec!J~y tlJ,.~~Jj~~and i_nt~g!neinto the ,bl()~~L
sary~~~~gy sour,~~' a_Q;·Q£~;.;~-~IT~a:'Jli~!~ gccui~; where they take .up..cholesterol and transportiC
Lip()lz~i~~~i§...the.hr:.~akdQ»;n o(Ji£~fls, resulting in the ha~k to theJi:ve;;; there it is e;x:c;;eted into bile.
pr()~,~c1L9ll .PfJ£~~~,fgllXggg§, ~~A~.h.i~~"'~.§~~J~i,~~~­ Chy[;~i~r;;(;" ~;~ formed fr~:rn ~xogenou;-fat
._,~y;Jfi',J-J,;:;,."7cfJi'•i.T)-\c"~,.,;';,.'"'-- -•--••-~-···~~·--~~-·~'"""'-'--·....2':•-F'I,.,

.~EgY; ~n£<:>1~1<:~t8£l~,RQ~i-¥LI\_etone bodies are pro- sotirc:~s and solubilized in the intestinal epitl1eliufi1.
duced ffl~t~L!Q~!LS~c!!~.can l,l,S_~them. T~e acc_u_l!lEJa- fh~y carry lipids.
- q'
;;;·~~scle
..---."'--'··'
an,5r:a<J}J22.S.~!issue." ·-
··-'"•"-'"·" •.• -d--'•-~; .• c•.• 7 .;.5 ,.•• ,;.,ood..o.;,c.,_~-- .-. ~~-""-·""-~""""' ~.-.c.=.-.•~,.._

tion of ketone bodies results in an acidotic state. - -


,_._•rl'-"':~, •....• ,_ ,. -·· __,, ,,,~~-~,··t-·.«c;-..:;;-r=~·"<'""''
Elevated levels of serum lipids can be related to a
Chronic num~er ok.ee·.nviron~.··.·In.t.:i·q··-.a~-tP. rs 9-!'. d.·".I.·sease s·t·a·~. ~.~j
(e.g., obesfty,hypo~pldi,s.w, neeh~c syndrom~).
~ J\.1?,-S:f.g_yjl§C:l1.lar_complications are a significant part
gf d!gJ2~tes. Patien:t's with diabetes are at a higher They can also be geneti~.~J!xJmk~~· Hyperlipidel!li.e..
as a result of a gen~ilc: llnJ< is referred to as [a,wilial
risk?f. ·c.·.·. om·_·
~!~l!M~rctlop., s,tr~, and coagulo~tht.es. The
p.li~ations,{.n:··.cluding~yper~siQ,~.'...·.m.yo- ~t'J!!1i+liil;£4.~111iq~:~b;;'>$d''"~ >Lc.""'~-~

mechanism-eywhich complications affec;tingthe large _!iY12.~-~Ji£Jst~m-i~"l§.inm~r!~BLI:>s:£.a u~e it~s .~. JB().~t


fiablc; risk_,factgr)n the; process of atherQ!>d~rp§is,
vessels occp,r is thrqugh atheroscleroti£J2Lwue .{_or-
mation. The exact relationship by which diabet;;
whi~h-~qm1llonly caus~s coron~r,J,:,",!:\£t~r,y. dj.~~~~~·
Ather()S(;~~.roticpl;;tque forrriatlonls thought to o<;:<::}J.t:_
"cause;-atherosclerosis is poorly understood.
--7-MicrpviJ.'scular complications (r~1lUQJ2-~l~Y an.,d fro~.£~S~R#R9- of hQ,ks on the ~~~££h$_ll~.!1~St~~·
n~phropiJct.l},y) and n~~E()paJhj(;;§ are often seen in di-
abetic patients. Diabetes-associated retinopathy is Asthma
one of the leading cq.uses of blindness in the United
Asthma is a chro11ic,i!k~~yjnflammatory di~ojq~
States. Diab~tic nt;p),J.ropathy isthe leaciing_ C:<i\11Se of
characterized by individual acute attacks that are
kidney failure in the United States. Renal chang~s iii:.:-
triggered by the envire>.gm~vt arid by genetic pr~.!:l.is~-­
- .8llik-tJJi~ccl~fR,~Q~~~,wlt,t;St,~~-~nd...s£1~~*i~ positions, It is characterized by obstruction of air~·
Q[}~~~lf~~~'f#1~;~~·~stood, three mech<1nisms ·~by ~' mucus hypersecretion,;-;na
i_!l.Jig,mm.<J.JWn. . ~""' . . .. --, -·"''~••a~-"- . . . ~~
seen in hyperglyce;mic states have been proposed as
the cause of microvascular complications:
Ei!..d.y_.acute::phas_e. Q!.9..U~b.osJ2asm occurs second-
~<) .a.J!ypersen~iti.vity QJ the hronchiqks to <!!1
I~
~ 1!11 Fonna!ign ofadyanced glyc;gsyl<]t\QD end products. .~JJ.vi~S?,,B!n.~DF.:~-L9r, .."l;llewic .irritant that initiate.s.ap_ ..
CL Sor,IJ,i!Q! formatio~ jp cells thrqugh the po!ygl t~l?mlinoglobulin_:_~ immune-mediated respoQ~~: (his
path'Yay, • ~~iipeswl:iiiels due ta;·refease-·orl11st<:lrf}"ill!;,
Oxidat~y~ .~tre~~. ~s a resultpf hype~gly~e~l~. and leukotpenesfrom mast cells, which cause inflam~
-~;~d"iia~~~l}}o/~)_ th~reby constrict"fug~
Hyperlipidemia <J.ix.w:ax, ?hort;~SF~!?xo..ru:.Q.g@..at<m are usually svc.:-
cessful... in controllingti}is
.
acute-phase bronchospasm.
\ .... " . "

Ci~~tr~~~~~~~~~·~~~~~~~~~~~~7el~~~~;~~
Hyperlipidemia, by definition, re ,ers to an aquormal
:Ieva~i~.,of fat iE th~ bloQg:;:_,CholesterQ], ~~~g_fc;.e.E_i_~~§,_ ~~~~!:;£ff5};~.!~:!,55~'f~<,,q,_;,._,}i["t--"t.l"""'~~«,""'lf-~-;,z;.tr;).!,'A~.t~- "'~··--· -~-----··"·· ~- -··· -····"·····r--,J?' <""--·- · ..-,- .,._ __,-

p§o.srKo.1fp!gs, and f!_ee fa!tfacids are i~p()_~ta.~~ lipiq~_ a late-phase irgJ;;tmmatory response. The relea~t: of

"~~:~·;;~~§'~~it)i~~~i~~llif:, ~~~~~~~,J~i~~d
found in the plasma oLth~_h_uman b_ody. Because
lipids are not water soluble, they a:;~-t~ansportedin
the pl<l~ma as lipoproteins, Four major clasae~. of lipoc rl?-acr<2r~<lf?,~~~"S,y~J~mis, ~P-4 ~!J.h:ll~~,sg,r~ic;,o~~~r£i~S.­
proteins e,xis!: are .often , needed•• to
··--r
co!ltrol
-- ...-.·,
thi~ late~phase:r~~£2Jl~e.
.. - . . . - . -- -~

~ y~ry)QY!-_density lipoproteins (VLDLs) are


f9.rm~st..ill1~Ls.~<;:reted,,hY<,W.eJi~er. They are rich ip
trigly~e,r.j£le_s_ and are_e.Yt:!l:!l1a}ly converted to low- 2..3a Key Points
de1lsityJ1_£gprot_eins ..~"·
F'>'-?'.~'-~·::-.:::.~~-'>;:;::-~~:- ,~:..'\."::'--:o..:Y·.~ .:.:_ - '
··
Low~denszty lipoproteins (LDLs) are formed Inflammation is a reaction of vascularized tissue
by cata..bg!!~DL()fVLI)~s. LDLs are the major and is a protective attempt by the body's defense
transpQJ;!~!:s of chci~sierol from the liver to'- mechanism to remove the harmful stimuli and re-
the tissues. .. , " turn the tissue to its normal structure or function.
Pathology and

11 Edema is the abnormal accumulation of fluids B. It promotes vascular dilation and increases
in the interstitial spaces of cells or tissues. It is vascular permeability.
controlled by hydrostatic and osmotic pressure. C. It degrades fibrin clots and activates com-
I! Hemorrhage is the loss or escape of blood from plement cascade.
the circulatory system, caused by trauma, vascu- D. Protein production is important in the
lar wall damage resulting from disease, or mal- membrane attack complex.
function of the body's normal mechanism to
maintain hemostasis. 2. Which of the following mediators of inflamma-
Ill! Thrombosis is the pathologic process of tion is stored in the granular tissue of mast cells?
formation of a blood clot, which is referred A. Arachidonic acid
to as a thrombus. B. Leukotrienes
11 Infarction is the process of forming an ischemic C. Plasmin
necrosis in the body tissue or organs. Infarctions D. Histamine
most commonly occur in cardiovascular tissue as
a result of thrombus formation. 3. Edema is caused by which of the following
!f;l Shock is a serious condition involving decreased
changes?
perfusion of tissues and organs because of inade-
quate blood flow. A. Decreased osmotic pressure in the plasma
I! Developmental defects originate in the embry-
B. Decreased hydrostatic pressure in the
onic period and are most commonly the result of capillaries
genetic or chromosomal abnormalities and envi- C. Decreased vascular permeability caused by
ronmental agents. inflammation
rn A neoplasm is an abnormal mass of tissue attrib- D. Increased excretion of sodium
utable to uncontrolled cellular proliferation.
Neoplasms can be benign or malignant in nature. 4. Purpuras are hemorrhages of what size?
!'!! Hypertension is defined as a repeatedly elevated A. <0.3 em
blood pressure exceeding 140 mmHg (systolic) B. 0.3-1 em
or 90 mmHg (diastolic). Hypertension can be c.~1cm
caused by abnormalities of the renin-angiotensin D.::;;0.3mm
system, disregulation of the sympathetic nervous
system, natriuretic hormone, and endothelial 5. Thrombus formation in the venous side of the
dysfunction. circulatory system is most commonly attribut-
rn Diabetes mellitus is an endocrine disease in able to
which the body does notproperly produce or A. vessel endothelium injury.
use insulin, resulting in hyperglycemia. Chronic B. increased blood flow.
hyperglycemia can result in macrovascular C. decreased blood flow.
complications (i.e., stroke, hypertension, and D. disseminated intravascular coagulation.
myocardial dysfunction) and microvascular
complications. 6. Thrombus formation originating in what part of
Hyperlipidemia is an abnormal elevation of fat the body often leads to a severe, life-threatening
in the blood, which can lead to coronary artery event known as pulmonary thromboembolism?
disease.
A. Left atrium of the heart
B. Deep veins of the lower extremities
C. Ascending aorta
2·4e Questions D. Aortic arch

1. Bradykinin, an important mediator of inflam- 7. Which of the following occurs in a patient ex-
mation, is formed following activation of the periencing hypovolemic shock?
kinin cascade. What is the principle action of
bradykinin? A. Cardiac output is decreased, and systemic
vascular resistance is increased.
A. It converts fibrinogen to fibrin, important B. Cardiac output is normal, and systemic
in clotting. vascular resistance is decreased.
The APhA Complete Review for the Foreign Pharmacy Graduate Equivalency Examination®

C. Cardiac output is increased, and systemic 12. In addition to directly causing vasoconstric-
vascular resistance is increased. tion, angiotensin II stimulates the release of
D. Cardiac output is decreased, and systemic what substance from the adrenal cortex?
vascular resistance is decreased.
A. Dopamine
B. Aldosterone
8. What is a developmental defect resulting from
C. Vasopressin
an abnormality in the cellular organization or D. Angiotensin-converting enzyme
arrangement called?
A. Disruption 13. Which of the following substances released by
B. Malformation endothelial cells is a pote!).t vasodilator?
C. Dysplasia A. Endothelin
D. Deformation B. Vasopressin
C. Dopamine
9. What mechanism is most commonly responsi- D. Nitric oxide
ble for causing Down syndrome?
A. Translocation of the Philadelphia chromo- 14. Which of the following substances released by
some (9 and 22) endothelial cells is a potent vasoconstrictor?
B. Deletion of a portion of the short arm of A. Nitric oxide
chromosome 5 B. Endothelin
C. Nondisjunction during meiotic segregation C. Renin
D. Robertsonian translocation of chromo- D. Aldosterone
some 21
15. Diabetic ketoacidosis occurs most frequently
10. Of the following findings, which is most likely in which type of diabetic patients?
an indication that a neoplasm is malignant?
A. Type 1 patients
A. Invasion into surrounding tissue B. Type 2 patients
B. Necrosis C. Gestational diabetes patients
C. Slow tumor growth D. Drug-induced diabetes patients
D. Atypia
16. Which of the following occurs as a result
11. Neoplasms are the result of alterations or of an immune-mediated .destruction of
mutations in the DNA sequence by carcino- beta cells?
gens, which disrupt normal cell regulation.
Tumor suppressor genes are an example of a A. Type 1 diabetes mellitus
regulatory gene found in the body. Which of B. Type 2 diabetes mellitus
the following alterations in the tumor sup- C. Gestational diabetes
pressor gene may cause the development of a D. Drug-induced diabetes
neoplasm?
17. The movement of leukocytes from a central
A. Mutation of both alleles of the tumor sup- location to the periphery of the blood vessel
pressor gene, causing overexpression of the during inflammation is referred to as
protein product
B. Mutation of one allele of the tumor sup- A. phagocytosis.
pressor gene, causing overexpression of B. margination.
the protein product C. sequestration.
D. exudation.
C. Mutation of one allele of the tumor sup-
pressor gene, causing inactivation of the
18. Which of the following substances are formed
protein product
through the cyclooxygenase pathway?
D. Mutation of both alleles of the tumor sup-
pressor gene, causing inactivation of the A. Leukotrienes
protein product B. Hageman facto.r
C. Prostaglandins terminating in the small branches of the pul-
D. Histamine monary artery, where it occludes blood flow.
7. A. Hypovolemic shock is due to an inadequate
What type of shock can be seen in some patients volume of circulating blood, thereby causing a
following a pulmonary thromboembolism? decrease in venous return, which decreases car-
A. Hypovolemic shock diac output. As compensation for the reduced
B. Distributive shock cardiac output, vasoconstriction occurs, thus
C. Cardiogenic shock increasing systemic vascular resistance.
D. Obstructive shock 8. C. Dysplasias are defects resulting from an
abnormality in the cellular organization or
Renin is a substance secreted in response to arrangement.
decreases in renal arteriolar pressure or blood 9. C. Most commonly, Down syndrome occurs
flow. What part of the kidney is responsible as an error during cell division. Other causes, al-
for secreting renin? though less likely, are mosaicism and Robertso-
nian translocation of chromosomes 21 and 14.
A. Peritubular capillary endothelial cells
10. A. Invasion of the tumor into surrounding tis-
B. Mesangial cells
sue is a characteristic of malignant neoplasms.
C. Lacis cells
Other findings suggestive of malignancy are
D. Juxtaglomerular cells
rapid growth and metastasis of the tumor.
11. D. Tumor suppressor genes are recessive, so
both alleles must be mutated for neoplastic
2·5s Answers growth to occur.
12. B. Aldosterone is responsible for sodium and
1. B. Bradykinin, a product of the kinin system water retention. Retention of sodium and water
that is derived from high molecular weight increases blood volume, thus increasing vascu-
kininogen, causes pain, promotes vasodilation, lar resistance.
and promotes vascular permeability. 13. D. Nitric oxide is a potent vasodilator released
2. D. Histamine, which produces vasodilation and by the endothelial cells in response to changes
increased vascular permeability once released, is in blood pressure.
stored in the granular tissue of mast cells. 14. B. Overstimulation of the production of endo-
3. A. Normal exchange of body water from the thelin may cause hypertension.
interstitial space and plasma is controlled by 15. A. Diabetic ketoacidosis is a potentially life-
hydrostatic pressure of the capillary blood and threatening complication most commonly seen
osmotic pressure regulated by plasma proteins.
in patients with type 1 disease.
If osmotic pressure in the plasma decreases, net
16. A. Type 1 diabetes mellitus is a result of
fluid movement will be out of the blood into
an immune-mediated destruction of beta cells
the interstitial space.
by T-lymphocytes, thereby causing insulin
4. B. Purpuras are widespread hemorrhages, be-
tween 0.3 and 1 em, found under the dermal deficiency.
surface. They are commonly caused by platelet 17. B. Margination is a process in which white
dysfunctions and vascular injury. blood cells, or leukocytes, relocate from their
5. C. Thrombus formation is due to three factors normal central location in the bloodstream to
known as Virchow's triad: injury or abnormal- the periphery along the endothelium wall.
ity of the endothelial wall of the vessel, de- 18. C. Prostaglandins and thromboxanes are pro-
creased blood flow, and changes in the normal duced from arachidonic acid through the cyclo-
process of coagulation. On the venous side, oxygenase pathway.
blood pressure is lower (as compared to arterial 19. D. Obstructive shock occurs when normal
blood) and most thrombi are formed because of blood flow is interrupted or obstructed. In cases
decreased blood flow. of obstructive shock, cardiac output is reduced
6. B. The most common source of embolus for- and systemic vascular resistance is increased.
mation is in the deep veins of the lower extrem- 20. D. Juxtaglomerular cells are responsible for se-
ities. Once the thrombus breaks free, it flows creting renin. Renin converts angiotensinogen
through the right side of the heart, ultimately to angiotensin I.
The APhA Complete Review for the Foreign Pharmacy Graduate Equivalency Examination®

2.. 6 References
e
SaseenJJ, MacLaughlin EJ. Hypertension. In: DiPiro
JT, Talbert RL, Yee GC, et al., eds. Pharmaco-
Beevers G, Lip GYH, O'Brien E. The pathophysiology therapy: A Pathophysiologic Approach. 7th ed.
of hypertension. BM]; 2001;322(7291):912-16. New York: McGraw-Hill; 2008:139-71.
Mitchell RN. Hemodynamic disorders, thrombo- Tripathy D, Rubenstein J. Neoplasia. In: McPhee
embolic disease, and shock. In: Kumar V, Abbas SJ, Lingappa VR, Ganong WF, eds. Pathophysiol-
AK, Fausto N, eds. Robbins and Cotran Pathologic ogy of Disease: An Introduction to Clinical Med-
Basis of Disease. 7th ed. Philadelphia: Elsevier icine. 4th ed. New York: McGraw-Hill; 2003:
Saunders; 2005:139-44. 91-112.
Nowack JT, Handford AG, eds. Essentials of Patho- Triplett CL, Reasner CA, Isley WL. Diabetes mellitus.
physiology: Concepts and Applications for Health In: DiPiro JT, Talbert RL, Yee GC, et al., eds,
Care Professionals. 2nd ed. Boston: McGraw-Hill; Pharmacotherapy: A Pathophysiologic Approach.
1999. 7th ed. New York: McGraw-Hill: 2008;1205-42.

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