1.
A 67-year-old woman slipped on
a scatter rug and fell with her right arm extended in an attempt to ease the
impact of the fall. She experienced immediate severe pain in the region of the
right collar bone and in the right wrist. Painful movement of the right arm was
minimized by holding the arm close to the body and by supporting the elbow with
the left hand.
Which of the following is the carpal bone most likely to dislocate anteriorly
and cause a form of carpal tunnel syndrome?
Correct Answer
C. Lunate
Explanation
The lunate bone tends to dislocate anteriorly into the transverse carpal arch, thereby entrapping the tendons of the extrinsic digital flexors and compressing the median nerve. The capitate is frequently fractured but does not tend to dislocate into the carpal arch. The hamate provides an anchor for the transverse carpal ligament and is, therefore, located lateral to the carpal tunnel. The navicular (scaphoid) bone has a tendency to fracture but does not dislocate into the carpal tunnel.
2.
A 67-year-old woman slipped on
a scatter rug and fell with her right arm extended in an attempt to ease the
impact of the fall. She experienced immediate severe pain in the region of the
right collar bone and in the right wrist. Painful movement of the right arm was
minimized by holding the arm close to the body and by supporting the elbow with
the left hand.
The fractured clavicle was reduced and the shoulder bandaged. The lunate bone
was surgically reduced. After eight weeks the bone had healed, but the patient
was found to have persistent loss of hand function. In addition to the region
of original paresthesia (palmar aspects of the thumb, index, and middle fingers
as well as a portion of the ring finger), which of the following areas should
also exhibit paresthesia
Correct Answer
A. Dorsal aspect of the distal pHalanges of the index and middle fingers
Explanation
In addition to supplying sensation to the palmar aspects of the thumb, index, and middle fingers as well as the radial portion of the ring finger, the median nerve also supplies the dorsal aspect of the terminal phalanx of those fingers. The dorsal web space between the thumb and index finger is supplied exclusively by the radial nerve. The fifth finger is supplied completely by the ulnar nerve. The central region of the palm is supplied by the superficial branch of the median nerve that arises proximal to the carpal tunnel and is not compromised by carpal tunnel syndrome because it passes superficial to the flexor retinaculum.
3.
A workman accidentally lacerated his wrist as
shown in the accompanying diagram. On exploration of the wound, a vessel and
nerve are found to have been severed, but no muscle tendons were damaged.
From the indicated location of the laceration,
which of the following is the involved nerve?
Correct Answer
D. Ulnar nerve
Explanation
The ulnar nerve descends along the postaxial (ulnar) side of the forearm. It passes lateral to the pisiform bone and under the carpal volar ligament, but superficial to the transverse carpal ligament. In the hand it divides into superficial and deep branches. The median nerve lies deep to the transverse carpal ligament where it is protected from superficial lacerations. Emerging from the carpal tunnel, it gives off the vulnerable recurrent branch to the thenar eminence. The superficial branch of the radial nerve supplies the dorsolateral aspects of the wrist and hand.
4.
A workman accidentally lacerated his wrist as
shown in the accompanying diagram. On exploration of the wound, a vessel and
nerve are found to have been severed, but no muscle tendons were damaged.
Which of the following thumb
movements would be abolished?
Correct Answer
B. Adduction
Explanation
The ulnar nerve innervates two of the intrinsic thenar muscles: the adductor pollicis and frequently the deep head of the flexor pollicis brevis. Because of the actions of the flexor pollicis longus and the superficial head of the flexor pollicis brevis, there would probably be no noticeable deficit in flexion. However, the ability to adduct the thumb would be lost with ulnar nerve injury.
5.
On the advice of a lawyer, a
27-year-old casino employee visited her personal physician because she found
she could no longer flex her thumb and was unable to deal cards. Examination
revealed weakness at the interphalangeal joint of the thumb as well as
difficulty in bending the tips of the index and middle fingers. She could make
a fist but had some difficulty in pinching with the thumb and index finger.
There was some forearm pain but no tingling or numbness.
These symptoms indicate damage to which of the following nerves?
Correct Answer
D. Anterior interosseus branch of the median nerve
Explanation
The anterior interosseus branch arises from the posterior portion of the median nerve in the cubital fossa and innervates the flexor pollicis longus, pronator quadratus, and portion of the flexor digitorum profundus inserting in the index and middle fingers. Thus, it mediates flexion of both the thumb and distal interphalangeal joints of the index and middle fingers. In addition, the anterior interosseus branch has no sensory distribution. The posterior interosseus branch of the radial nerve supplies abductors of the thumb and extensors of the thumb and fingers. The palmar branch of the ulnar nerve is purely sensory. The recurrent branch of the median nerve innervates muscles of the thenar compartment (e.g., flexor pollicis brevis), and damage may result in some difficulty in flexion of the thumb, but not of the index and middle fingers. The digital branches of the ulnar nerve supply the ring and little fingers and are sensory.
6.
On the advice of a lawyer, a
27-year-old casino employee visited her personal physician because she found she
could no longer flex her thumb and was unable to deal cards. Examination
revealed weakness at the interphalangeal joint of the thumb as well as
difficulty in bending the tips of the index and middle fingers. She could make
a fist but had some difficulty in pinching with the thumb and index finger.
There was some forearm pain but no tingling or numbness.
What type of joint is the interphalangeal joint?
Correct Answer
B. Ginglymus
Explanation
A joint between phalanges is termed a ginglymus or "hinge" joint. It allows movement in only one plane (flexion and extension are opposite movements in the same plane). The hip joint is typical of a ball and socket joint. This type of joint permits movement in all three axes and in a combination termed circumduction. A gomphosis is the type of joint made by a tooth with bone. The carpometacarpal joint of the thumb typifies a saddle joint. It permits movement in two axes. The radiocarpal joint at the wrist is an example of an ellipsoidal joint. It is biaxial, but the excursion of movement is longer in one axis.
7.
A patient experienced a
prolonged stay in one position during a recent surgery and postoperative
recovery that resulted in compression of the common peroneal nerve against the
fibular head. Which of the following motor deficits would be most likely to
occur?
Correct Answer
D. Loss of eversion
Explanation
Compression of the common peroneal nerve would affect all muscles innervated by this nerve, including tibialis anterior, peroneus longus, and extensor digitorum longus. Loss of dorsiflexion and eversion is usually complete. The extensors of the knee joint (quadriceps femoris) are supplied by the femoral nerve, whereas the flexors of the knee joint (the hamstrings and gracilis) are supplied by the tibial nerve and obturator nerve, respectively. The gastrocnemius and soleus muscles are the principal plantar flexors of the foot and are innervated by the tibial nerve. The popliteus is the prime medial rotator of the tibia and is also innervated by the tibial nerve.
8.
A patient experienced a prolonged stay in one
position during a recent surgery and postoperative recovery that resulted in
compression of the common peroneal nerve against the fibular head.
In the above scenario, inversion of the foot
is still intact although weakened. Which of the following muscles supplies this
action?
Correct Answer
A. Tibialis posterior
Explanation
Following compression injury of the common peroneal nerve, eversion is usually completely impaired, whereas loss of inversion is only partial. Tibialis posterior is a powerful inverter of the foot and is innervated by the tibial nerve; therefore, its action would remain. The peroneus longus is an everter of the foot, and its action is lost by compression of the common peroneal nerve. The extensor digitorum longus is innervated by the common peroneal nerve but is an everter of the foot. The quadratus plantae is a flexor of the toes and is innervated by the lateral plantar branch of the tibial nerve.
9.
. Primary oocytes have
developed by the time of birth. From puberty to menopause, these germ cells
remain suspended in meiotic prophase. The oocyte of a mature follicle is
induced to undergo the first meiotic division just before ovulation as a result
of which of the following hormonal stimuli?
Correct Answer
E. The surge of luteinizing hormone (LH) initiated by high estrogen titers
Explanation
A midcycle surge of luteinizing hormone (LH) triggers the resumption of meiosis and causes the FSH-primed follicle to rupture and discharge the ovum. Under the influence of LH, the ruptured follicle is transformed into a corpus luteum, which produces progesterone. Follicle-stimulating hormone and LH produced in the adenohypophysis result in growth and maturation of the ovarian follicle. Under FSH stimulation, the theca cells proliferate, hypertrophy, and begin to produce estrogen.
10.
A 26-year-old man contracted
viral influenza with an unremitting fever of 39.5°C (103°F) for three days.
Because spermatogenesis cannot occur above a scrotal temperature of 35.5°C
(96°F), he was left with no viable sperm on his recovery. Which of the
following is the approximate time required for spermatogenesis, spermiogenesis,
and passage of viable sperm to the epididymis?
Correct Answer
D. 2 months
Explanation
In man the time required for the progression from spermatogonium to motile spermatozoon is about two months (61 to 64 days). Spermatogenesis, the process by which spermatogonia undergo mitotic division to produce primary spermatocytes, occurs at 1°C (2°F) below normal body temperature. Subsequent meiotic divisions produce secondary spermatocytes with a bivalent haploid chromosome number and then spermatids with a monovalent haploid chromosome number. The maturation of the spermatid, spermiogenesis, results in spermatozoa. Morphologically adult spermatozoa are moved to the epididymis where they become fully motile.
11.
Implantation of the conceptus at which site in
the accompanying diagram of the female reproductive system could result in
excessive, perhaps fatal, vaginal bleeding before parturition?
Correct Answer
B. B
Explanation
Implantation of the conceptus low on the uterine wall near the cervical opening (os) could result in growth of the placenta between the embryo and the cervical os (placenta previa). The placenta could become dislodged from the uterine wall before, as well as during, delivery, resulting in rapidly fatal hemorrhage. Implantation at site A (the uterine tube or oviduct) results in rupture of the oviduct wall, whereas implantation on the ovary (C) would result in destruction of that organ. Implantation could also occur in the wall of the peritoneal cavity (D). Implantation normally occurs in the superior posterior or posterolateral walls of the uterus (E).
12.
In the developing human embryo, most of the
internal organs begin to form in which month?
Correct Answer
B. Second
Explanation
Formation of most internal organs occurs during the second month, the period of organogenesis. The first month of embryonic development generally is concerned with cleavage, formation of the germ layers, and establishment of the embryonic body. The period from the ninth week to the end of intrauterine life, known as the fetal period, is characterized by maturation of tissues and rapid growth of the fetal body.
13.
The primitive uteroplacental circulation is
established during which period of fetal development?
Correct Answer
B. Second week
Explanation
During the second week of fetal development, lacunar spaces develop between cells of the syncytiotrophoblast, particularly in the region of the embryonic pole as the conceptus invades the endometrium. Endometrial capillaries in this region become dilated and engorged with blood to form sinusoids. The syncytial cells direct erosion of the endothelium of the maternal capillaries, allowing maternal blood to enter the lacunae and bathe the syncytial cells. This establishes the uteroplacental circulation. During the second week, primary villi consist of projections of syncytial cells surrounding a core of cytotrophoblast cells. During the third week, the villus core is invaded by mesodermal cells to form a secondary villus. Cells of the mesodermal core will then differentiate to form capillaries and blood cells by the end of the third week (tertiary villus). These vessels become connected to the fetal circulation early in the fourth week.
14.
Which places the developing heart in the
presumptive thoracic region cranial to the septum transversum?
Correct Answer
C. Cranial folding
Explanation
Initially, the developing cranial portion of the neural tube lies dorsal and caudal to the oropharyngeal membrane. However, overgrowth of the forebrain causes it to extend past the oropharyngeal membrane and overhang the cardiogenic area. Subsequent growth of the forebrain pushes the developing heart ventrally and caudally to a position in the presumptive thoracic region caudal to the oropharyngeal membrane and cranial to the septum transversum that will form the central tendon of the diaphragm. Gastrulation is the process by which epiblast cells migrate to the primitive streak and become internalized to form the mesodermal and endodermal germ layers. Neurulation refers to formation of the neural tube from surface ectoderm. Lateral folding of the embryo forms the endoderm tube and surrounding concentric layering of mesoderm and ectoderm.
15.
Which of the following is in
direct contact with maternal blood in lacunae of the placenta?
Correct Answer
D. Cells of the syncytiotropHoblast
Explanation
In the developing fetus, the maternal blood is in direct contact with the syncytiotrophoblast. During implantation, the syncytiotrophoblast invades the endometrium and erodes the maternal blood vessels. Maternal blood and nutrient glandular secretions fill the lacunae and bathe the projections of syncytiotrophoblast. Primary villi consist of syncytiotrophoblast with a core of cytotrophoblast cells. In secondary villi, the cytotrophoblast core is invaded by mesoderm and subsequently by umbilical blood vessels in tertiary villi.
16.
During which of the
following periods is the embryo most susceptible to environmental influences
that could induce the formation of nonlethal congenital malformations?
Correct Answer
C. The fourth through eighth weeks of fetal life
Explanation
Exposure of the embryo to harmful environmental factors (teratogens), such as chemicals, viruses and/or radiation, can occur at any time. During the fourth through eighth weeks of embryonic life, organ systems are developing and are most susceptible to teratogens. During this time, each organ system has its own specific period of peak susceptibility. Exposure of the embryo to teratogens during the first three weeks of fetal life generally induce spontaneous abortion and are, therefore, lethal. After the eighth week of intrauterine development, teratogenic exposure generally results in retardation of organ growth rather than in new structural or functional changes.
17.
During a visit to her
gynecologist, a patient reports she received vitamin A treatment for her acne
unknowingly during the first two months of an undetected pregnancy. Which of
the following organ systems in the developing fetus are most likely to be
affected?
Correct Answer
E. The skeletal and central nervous systems
Explanation
Vitamin A is a member of the retinoic acid family. Retinoic acid directs the polarity of development in the central nervous system, the axial skeleton (vertebral column), and probably the appendicular skeleton as well. Retinoic acid turns on various combinations of homeobox genes, depending on tissue type and location (distance and direction from the source of retinoic acid). Exogenous sources of retinoic acid may induce the wrong sequence or combination of homeobox genes, leading to structural abnormalities in the nervous and skeletal systems. The other organ systems listed are not as susceptible to vitamin A.
18.
Which of the following forms
from paraxial mesoderm?
Correct Answer
D. Biceps brachii
Explanation
The muscles of the extremities form from the somites that are derived from paraxial mesoderm. The intermediate mesoderm is the origin of the urogenital systems and the adrenal cortex. The adrenal medulla forms from neural crest. The humerus forms from somatopleuric mesoderm, but the muscles of the extremities are of somite origin. The masseter is a muscle of mastication formed from the first branchial arch and innervated by branchial visceral efferent (special visceral efferent) fibers from the nucleus ambiguus compared with the general somatic efferent innervation of the biceps and other muscles, not of branchial arch origin.
19.
In the developing embryo, the edge of the
ectoderm is continuous with which of the following?
Correct Answer
B. Amniotic membrane
Explanation
Each of the embryonic germ layers is continuous with an extraembryonic structure. The ectoderm is continuous with the amniotic membrane, the endoderm with the lining of the yolk sac, and the embryonic mesoderm with the extraembryonic mesoderm.
20.
Which of the following is
primarily responsible for the polyanionic charge on the outer surface of the
plasma membrane?
Correct Answer
B. Glycoprotein
Explanation
The carbohydrate of biological membranes is found in the form of glycoproteins and glycolipids rather than as free saccharide groups. The polyanionic charge of the membrane is produced by the sugar side chains on the glycoproteins and glycolipids. Glycoproteins often terminate in sialic acid side chains, which impart a negative (polyanionic) charge to the membrane. Similarly, the glycolipids (a/k/a glycosphingolipids), particularly the gangliosides, terminate in sialic acid residues with a strong negative charge. Cholesterol alters membrane fluidity. It is amphipathic (hydrophilic and hydrophobic properties). It acts by reducing the packing of lipid acyl groups through its steroid ring structure and hydrocarbon tail and cementing hydrophilic regions of the membrane through interactions with its hydroxyl (OH–) region. Peripheral membrane proteins are found on the cytosolic leaflet of the membrane bilayer. Integrins are heterodimeric receptors that bind with extracellular matrix (ECM) molecules such as laminin and fibronectin.
21.
Glycophorin is a
single-pass, transmembrane glycoprotein found in the erythrocyte (RBC). Which
of the following is an expected characteristic of this protein?
Correct Answer
D. The polypeptide chain crosses the lipid bilayer in an alpHa -helix conformation
Explanation
As a transmembrane protein, glycophorin traverses the membrane and crosses the lipid bilayer in a single-pass alpha -helix conformation. The hydrophobic portion spans the lipid bilayer, and the hydrophilic carboxyl end is exposed to the cytosol, whereas the hydrophilic amino end is exposed to the extracellular surface. The oligosaccharides are found on the hydrophilic amino terminus where the negative surface charge is generated. The oligosaccharides are degraded by carbohydrate hydrolysis. Harsh detergent treatment is required for isolation of transmembrane proteins, such as glycophorin, compared with peripheral proteins, such as spectrin and ankyrin, that can be isolated by mild extraction methods.
22.
Which of the following is
the function of the large subunit of the ribosome?
Correct Answer
C. Catalyze peptide bond formation
Explanation
The large subunit of the ribosome catalyzes peptide bond formation by activation of peptidyl transferase. The small ribosomal subunit contains the peptidyl-tRNA-binding (P) site that binds the tRNA molecule attached to the carboxyl end of the growing end of the polypeptide chain. The small subunit also contains the aminoacyl-tRNA-binding (A) site that holds the incoming tRNA and amino acid. The initiation factors are loaded on the small ribosomal subunit that must locate the AUG (start) codon to initiate protein synthesis. This occurs before binding of the large subunit. In addition, the initiator tRNA containing methionine provides the amino acid necessary to start protein synthesis. The initiator tRNA is also located on the small subunit. It resides at the P site (the normal peptidyl site) even though it is an aminoacyl-tRNA. This occurs before binding to the mRNA. Therefore, the initiation phase of protein synthesis is regulated by the small subunit of the ribosome. Ribosomes are composed of both protein and RNA (predominately rRNA, but also mRNA and tRNA). Single ribosomes are involved in synthesis of cystolic proteins. Polyribosomes (linked by mRNA) synthesize proteins that are translocated into the cisternal space of the rough endoplasmic reticulum (RER) and destined for export or specific organelles.
23.
Which of the following events occurs in the
rough endoplasmic reticulum?
Correct Answer
A. Core glycosylation of proteins
Explanation
The rough endoplasmic reticulum (RER) is the site of core glycosylation of proteins using the membrane-bound lipid carrier, dolichol, catalyzed by an oligosaccharide transferase. This is N-linked glycosylation, which occurs by an en bloc method in which dolichol is added to the protein. O-linked glycosylation occurs in the Golgi by a mechanism involving oligosaccharide transferases. It does not occur en bloc. N-Linked oligosaccharides are the most common oligosaccharides found in glycoproteins. They contain sugar residues linked to the NH2 amide nitrogen of asparagine. O-linked oligosaccharides have sugar residues linked to hydroxyl groups on the side chains of serine and threonine and are less common than the N-linked species. O-linkage is catalyzed by glycosyltransferase enzymes in the Golgi, not the rough endoplasmic reticulum. However, in both the ER and the Golgi apparatus, the enzymes are located on the luminal side of these cisternal structures. The addition occurs sugar by sugar rather than en bloc as occurs in the rough endoplasmic reticulum for the N-linked oligosaccharides.
The RER is associated with ribosomes involved in the synthesis of proteins for export, but also segregation to the plasma membrane as well as to the membranes of mitochondria and peroxisomes. SER is involved in lipid synthesis and is extensive in cells actively involved in lipid production, such as the cells of the adrenal cortex. An integral membrane protein of SER is also involved in the synthesis and breakdown of glycogen (glycogenolysis). The amount of SER may be increased in cells such as hepatocytes by the systemic administration of drugs such as phenobarbital. Cellular components are degraded in lysosomes. The diversity in oligosaccharides is produced by selective removal of glucose and mannose from the core oligosaccharide. This trimming process begins in the RER before reaching the Golgi, where the final mannose-residue trimming occurs. Protein sorting and sulfation are carried out in the Golgi apparatus.
24.
. In Zellweger syndrome,
tissue shows the presence of empty peroxisomes. Which of the following findings
would you expect in patients?
Correct Answer
B. Inability to detoxify alcohol
Explanation
Individuals suffering from Zellweger syndrome are unable to detoxify alcohol because of the absence of alcohol dehydrogenases in the peroxisomes. In this syndrome, peroxisomes are empty because of the failure of the signal system that sorts protein to this organelle. Because the peroxisome lacks a genome or synthetic machinery, it must import all proteins. In the case of Zellweger syndrome, it appears that the defect is in the peroxisomal membrane, but errors or absence of the peroxisomal signal sequence would result in the same symptom. Peroxisomes were first identified in liver and kidney cells, which have large numbers of peroxisomes because of their function in detoxification and waste removal. Peroxisomes protect the cell by removal of H2O2 and the detoxification of alcohol. The absence of catalase and other proteins of the peroxisome would result in dramatically reduced detoxification capacity. The SER is the site of barbiturate detoxification, but the process is not dependent on peroxisomes. Lysosomes, mitochondria, and protein synthetic activity should not be affected in Zellweger syndrome.
25.
Movement of vesicles and
organelles from the perikaryon of the neuron to the axon terminus occurs along
which of the following?
Correct Answer
C. Microtubules
Explanation
Vesicles and organelles move unidirectionally along microtubules from the perikaryon of a neuron to the axon terminus. This process is driven by the microtubule motor, kinesin, an ATPase that hydrolyzes ATP to ADP, providing the energy required for vesicular movement. Microtubules are composed of tubulin and are involved in motility as the principal protein in the composition of the axoneme (the core of the cilium or flagellum). Microfilaments (thin filaments) are composed of actin, the most abundant protein in cells of eukaryotes. They are involved in cell motility and changes in cell shape. Myosin is the main constituent of the thick filament that binds to actin and functions as an ATPase activated by actin. Intermediate filaments that are "intermediate" in diameter (8 to 10 nm) between thin and thick filaments, are of four different types. Type I is composed of the acidic, neutral, and basic keratins (also known as the cytokeratins) and is found specifically in epithelial cells. Type II intermediate filaments are composed of vimentin, desmin, or glial fibrillary acidic protein. Vimentin is found in cells of mesenchymal origin, desmin in muscle cells, and glial fibrillary acidic protein primarily in astrocytes. Type III intermediate filaments are neurofilament proteins found in neurons. Type IV intermediate filaments consist of nuclear lamins A, B, and C and are associated with nuclear lamina of all cells.
26.
Which of the following molecules forms the
coating of vesicles involved in endocytosis and exocytosis?
Correct Answer
A. Clathrin
Explanation
Clathrin is an important protein that forms the coating of coated pits and vesicles involved in endocytosis and the retrieval of membrane following exocytosis. Intermediate filaments are important cytoskeletal elements with some specificity that depends on the origin of the cells in question. Vimentin is specific for cells of mesenchymal origin, such as fibroblasts and chondrocytes. Actin is the protein found in thin filaments. It is also a cytoskeletal component found in the cytoplasm of red blood cells and other eukaryotic cells. Spectrin heterodimers form tetramers that interact with actin and provide flexibility and support for the membrane. The protein ankyrin "anchors" the band 3 protein to the spectrin-membrane skeleton. This connection is often described as the indirect binding of band 3 protein to the cytoskeleton (spectrin tetramers) of the red blood cell. The band 3 protein is known to be an anion transport protein of the red blood cell.
27.
Which of the following
cellular compartments is the sorting and packaging station within the Golgi
apparatus?
Correct Answer
D. Trans-Golgi network
Explanation
The trans-Golgi network (TGN) serves as a sorting station for proteins destined for various organelles, including the plasma membrane, and protein for export from the cell. Golgi-derived transport and secretory vesicles bud off from the TGN. Transitional elements are derived from the endoplasmic reticulum (ER) and carry proteins and lipids from the endoplasmic reticulum to the cis-face of the Golgi. The Golgi apparatus plays an important role in the processing of proteins for secretion. It is divided into four regions: cis-face, medial compartment, trans-face, and the trans-Golgi network (TGN). The cis-face of the Golgi receives the transitional elements and participates in phosphorylation (e.g., in the synthesis of lysosomal oligosaccharides). The medial compartment is responsible for the removal of mannose and the addition of N-acetylglucosamine. The trans-face is responsible for the addition of sialic acid and galactose.
28.
The figure below is a diagram of the
phosphoinositide (PI) cycle and related regulatory processes. Which of the
following is the function of molecule A?
Correct Answer
C. Hydrolysis of PIP2 to form DAG and IP3
Explanation
Molecule A in the figure is phospholipase C that catalyzes the formation of diacylglycerol (DAG) and inositol triphosphate (IP3) from phosphatidylinositol 4,5-bisphosphate (PIP2). Phosphoinositides are important intracellular second messengers. The phosphoinositide (PI) cycle illustrated in the figure is based on the formation of PIP2 in the inner leaflet of the plasma membrane. The breakdown of PIP2 leads to the formation of the key functional agents of the PI cycle. The process begins with the binding of a ligand to its G protein–linked receptor on the cell surface. In this case, the trimeric G protein is known as Gq. It activates a phosphoinositide-specific phospholipase C. PI-specific phospholipase C hydrolyzes PIP2 to form DAG and IP3. These two molecules function differently to regulate intracellular function. IP3 functions in the mobilization of calcium while DAG activates protein kinase C, leading to multiple phosphorylations of cytosolic proteins. DAG (B in the figure) is responsible for activation of protein kinase C (so-called because of its Ca2+ dependency), which is labeled D. The protein kinase C phosphorylates specific serine and threonine residues in the cytosol, and it functions in many cells to alter gene transcription. In contrast, IP3 functions to mobilize Ca2+ (E) by binding to IP3-gated Ca2+-release channels in the membranes of the endoplasmic reticulum. The two intracellular messenger pathways do interact in that elevated Ca2+ translocates protein kinase C from the cytosol to the inner leaflet of the plasma membrane. Gi is the inhibitory G protein that leads to 5'-AMP production through the action of phosphodiesterase instead of cAMP.
29.
Inclusion cell disease is
characterized by the absence of lysosomal hydrolytic enzymes. Normal hydrolytic
enzymes are uncharacteristically found in the blood. Which of the following is
the most likely cause for this defect?
Correct Answer
D. Absence of mannose-6-pHospHate on lysosomal enzymes
Explanation
In inclusion (I) cell disease, there is an absence or deficiency of N-acetylglucosamine phosphotransferase and an absence of mannose-6-phosphate receptors on lysosomal enzymes. This results in mis-sorting to the secretory pathway and release from the cell by exocytosis. The absence of mannose 6-phosphate (normally added in the cis-Golgi) prohibits segregation of lysosomal enzymes that normally occurs in the trans-Golgi through the action of mannose-6-phosphate receptors. Lysosomal enzymes are secreted into the bloodstream, and undigested substrates build up within the cells. There is normal expression of the genes encoding the hydrolases, but a misdirection of the intracellular sorting signal for these hydrolytic enzymes. Loss of the mannose 6-phosphate receptor would have a similar effect in constitutive release of lysosomal enzymes. Overexpression of mannose 6-phosphate receptors could lead to increased shuttling to lysosomes. KDEL is the signal used for retrieval of proteins from the Golgi back to the endoplasmic reticulum. SNAREs [soluble-N-ethylemalemide sensitive factor (NSF) attachment protein receptor] are the receptors for SNAPs [soluble-N-ethylemalemide sensitive factor (NSF) attachment protein] and bind vesicles to membranes. Trafficking to other structures, such as the nucleus and mitochondria, is regulated by nuclear localization signals (NLS) or an N-terminal signal peptide, respectively.
30.
Which of the following proteins binds to
membrane proteins and serves as a scaffold to support the nuclear envelope?
Correct Answer
A. Lamins
Explanation
Lamins are a subclass of intermediate filaments including three nuclear proteins: lamins A, B, and C. The lamins differ from other intermediate filament proteins in some structural respects, but more importantly in the presence of a nuclear import signal. The lamins form the core of the nuclear lamina, interact with nuclear envelope proteins, and play a role in the maintenance of the shape of the nucleus. Phosphorylation of intermediate filaments leads to disassembly as occurs with the lamins. The disassembly of lamins results in the dissolution of the nuclear envelope in prometaphase of the cell cycle. Dephosphorylation of the lamins is associated with the reassembly of the nuclear envelope in telophase. Porins are transmembrane proteins that form pores in the outer membrane of mitochondria and gram-negative bacteria. Chaperonins are cytosolic protein chaperones essential for the proper unfolding of proteins.
31.
A metaphase-blocking dose of colchicine works
by which of the following mechanisms?
Correct Answer
D. Inhibition of tubulin polymerization
Explanation
At a mitosis-inhibiting dose, colchicine functions by binding specifically and irreversibly to tubulin. The colchicine-tubulin complex is added at the positive end of the kinetochore, but it inhibits further addition of tubulin. The result is a biochemical capping of the tubulin at the growth end, preventing further tubulin addition. Cells are blocked in metaphase and cannot escape because microtubule motors are unable to function in generating the forces required for anaphase. At higher doses of colchicine, cytosolic microtubules depolymerize. Actin and myosin are involved in cytokinesis (the division of cytoplasm), whereas tubulin and the microtubules regulate separation of the daughter nuclei and their contents. Taxol, like colchicine, inhibits mitosis, but it uses a different mechanism. Taxol binds and stabilizes microtubules, causing a disruption of microtubule dynamics and inhibition of mitosis. Taxol and colchicine are similar in binding only to alpha ,beta -tubulin-dimers and microtubules.
32.
An obese 18-year-old male
patient presents with small, firm testes, a small penis, little axillary and
and facial hair, azoospermia, gynecomastia, and elevated levels of plasma
gonadotropins. He has had difficulty in social adjustment throughout high
school, but this has worsened and he has been referred for genetic and
endocrine screening. The karyotype from peripheral blood leukocytes would most
likely show how many Barr bodies?
Correct Answer
B. One
Explanation
Cells from a patient with the most common form of Klinefelter syndrome (47,XXY genotype) will have one inactive X chromosome and, therefore, one Barr body. The formula is the number of Barr bodies equals the number of X chromosomes minus one. Klinefelter syndrome occurs about 1:500 males and is due to meiotic nondisjunction of the chromosomes. The nondisjunction is more frequent in oogenesis than spermatogenesis, and increased occurrence is directly proportional to increasing maternal age. Klinefelter may occur as 47,XXY, 48,XXYY, 48,XXXY, and 49,XXXXY. A combination of abnormal and normal genotype occurs in mosaic individuals who generally have less severe symptoms. Females have two X chromosomes, one of maternal and the other of paternal origin. Only one of the X chromosomes is active in the somatic, diploid cells of the female; the other X chromosome remains inactive and is visible in appropriately stained interphase cells as a mass of heterochromatin. Detection of the Barr body (sex chromatin) has been an efficient method for the determination of chromosomal sex and abnormalities of X-chromosome number; however, it is not definitive proof of maleness or femaleness. The genotypic sex of Klinefelter syndrome and XXX individuals would be male and female as determined by the presence or absence of the testis-determining Y chromosome. In Turner's syndrome (XO), no Barr bodies would be present. In comparison, "superfemales" (XXX) would possess two inactive X chromosomes (2 Barr bodies) and one active X chromosome. Buccal scrapings for Barr body analysis are being used less—chromosomal analysis is becoming the standard test now.
33.
Pemphigus is a disease in
which patients make antibodies to one of their own skin desmogleins involved in
the formation of the junctional complexes between cells. Which of the following
junctional complexes would be most affected in this disease?
Correct Answer
A. Macula adherens
Explanation
In pemphigus, autoantibodies to desmoglein (a member of the cadherin protein family) result in disruption of the macula adherentes (plural) or desmosomes. The desmogleins are the transmembrane linker proteins of the desmosome. Specific desmogleins are the target of the autoantibodies in different forms of the disease. Cadherins are CA2+-dependent transmembrane-linker molecules essential for cell-to-cell contact, so their disruption in pemphigus leads to severe blistering of the skin because of disrupted cell-cell interactions early in the differentiation of the keratinocyte (epidermal cell) and excessive fluid loss.
34.
Which of the following is
found only in the lamina densa of the basement membrane?
Correct Answer
C. Type IV collagen
Explanation
Type IV collagen forms the electron-dense lamina densa of the basement membrane. At the light microscopic level, a uniform basement membrane is visible under epithelia. Ultrastructurally, basement membranes are composed of one or two electron-lucent areas (laminae rarae), that contain fibronectin, laminin, proteoglycans, and adhesive proteins. Deep to the lamina rara is the lamina densa with its electron-dense type IV collagen. The third layer is the reticular layer that is formed by the underlying connective tissue. This reticular lamina is composed of collagen fibrils formed by the connective tissue below the epithelium (basement membrane = basal lamina + reticular lamina). Fibronectin is found primarily on the connective tissue side of the basement membrane, whereas laminin is found toward the epithelial side.
35.
Which of the following definitively
characterizes the basolateral membrane?
Correct Answer
D. The presence of Na+/K+ ATPase
Explanation
The basolateral membrane is characterized by the ubiquitous presence of the Na+/K+-ATPase, responsible for generating the Na+/K+ gradient of the cell. Na+ is pumped out of the cell, and K+ is pumped into all animal cells by this ATP-dependent pump. Ouabain is a specific inhibitor of the Na+/K+ ATPase. Radioactive forms of this inhibitor are used to label Na+/K+-ATPase in the membrane in experimental studies. Hormonal receptors are found on both apical and basolateral surfaces. Neurotransmitter receptors are more prevalent on the basolateral surfaces. Exocytosis and endocytosis may occur across both apical and basolateral membranes as does ion transport. The apical surface of cells is covered by a glycocalyx that consists of oligosaccharides linked to glycoproteins and glycolipids and proteoglycans. The presence of these sugars results in a negative (polyanionic) charge on the luminal surface. Polarity of the epithelial cell is based on these apical and basolateral specializations of the cell membrane.
36.
Which of the following
statements best characterizes basal folds in epithelial cells?
Correct Answer
D. They are associated with cells involved in active transport
Explanation
Basal folds are modifications of the basal region of the cell. These deep infoldings of the basal plasma membrane increase surface area and compartmentalize numerous mitochondria that provide energy for ionic and water transport. Distal tubule cells of the kidney and striated duct cells of the submandibular glands possess prominent basal infoldings that are observed at the light microscopic level as basal striations.
37.
In Kartagener's syndrome,
which of the following causes ciliary immotility?
Correct Answer
C. Lack of dynein arms
Explanation
In immotile cilia syndrome, the outer dynein arms may be absent and microtubular arrangements are abnormal. The result is failure of normal ciliary action. Chronic bronchial and sinus infections are common occurrences in these patients because the cilia are unable to remove foreign material. Infertility in the male is due to absence of normal ciliary proteins in the flagella of the spermatozoa. Infertility in the female may be related to problems in movement of the ovum through the oviduct. Many of the patients diagnosed with immotile cilia syndrome are observed to have a lateral transposition of the major organs of the body (situs inversus). Normal ciliary action may be required for normal positioning of organs during development.
38.
Which of the following are the structures
labeled by the asterisks in the photomicrograph below?
Correct Answer
A. Taste buds
Explanation
The structures shown in the photomicrograph are the taste buds. They are found within the epithelial lining of the circumvalate, foliate, and fungiform papillae of the tongue and open to the surface via a pore. They consist of a barrel-like arrangement of tall supporting and receptive cells in addition to a small population of basal cells that may serve as precursors to the more specialized cells. Receptive cells contain vesicles similar to neuronal synaptic vesicles. The vesicles are found near the base of the cell in close proximity to neuronal dendritic endings near the cell surface. Sympathetic ganglia are characterized by large euchromatic nuclei with prominent nucleoli. They are not found within epithelia. Filiform papillae are rasplike projections of the lingual epithelium. They do not possess taste buds. The von Ebner's glands are present in the connective tissue underlying the lingual epithelium near the circumvallate papillae. Their serous secretions empty via ducts into deep grooves surrounding each papilla. Sebaceous glands are located in the dermis of most regions of the skin and secrete lipids and cholesterol via a holocrine process.
39.
The figure below represents a cross section of a
cilium. Which of the following is the function of the structure labeled C?
Correct Answer
D. Regulation of the ciliary beat
Explanation
In the diagram of the cilium, the radial spokes (C) extend from the doublets toward the central pair and are involved in regulation of the ciliary beat. Cilia and the structurally similar flagella produce wavelike bending movements for propulsion of materials over the surface (e.g., movement of mucus in the tracheal epithelium) or cellular movement (e.g., that of sperm). The arrangement of the ciliary axoneme is described as a "9 + 2" structure that consists of nine outer doublets (E) of complete "A" and incomplete "B" tubules that surround a central pair of complete tubules (F). The dynein arms (B) project from the nine doublets and produce interaction between the doublets, which causes bending. Dynein is an ATPase that provides the energy for bending. The nexin links (D) hold neighboring doublets together and inhibit sliding between doublets. The inner or central sheath (A) surrounds the central doublet.
40.
Which of the following
structures is responsible for the linkage of the intermediate filament network
of cells to the basal lamina?
Correct Answer
C. Hemidesmosomes
Explanation
The hemidesmosome interacts with the extracellular matrix molecules within the basal lamina through intermediate filament proteins. The hemidesmosomes combined with the desmosomes act to distribute tensile forces through the epithelial sheet and the supporting connective tissues.
Junctional complexes are summarized in the table below.
Classification Type Function Interactions
Occluding Zonula occludens (tight junction) Prevents passage of luminal substances; confers epithelial tightness or leakiness; maintains apical vs basolateral polarity Intramembranous sealing strands occlude the space between cells (no. of strands directly proportional to tightness of epithe lium)
Anchoring Zonula adherens Mechanical stability—cohesive function of cell groups, important during embryonic folding; transmits motile forces across epithelial sheets Link actin filament network be tween cells, cadherins are transmembrane linkers
Focal contacts Attach cells to the ECM Link actin filament network of cell to integrins in ECM; actin-binding proteins form link
Anchoring (cont.) Desmosome (macula adherens) Spot welds (rivets) provide high tensile strength and resist shearing forces, numerous in stratified squamous epithelia Link intermediate filaments to transmembrane proteins (cadherins: desmogleins and desmocollins). Linkage through plaque proteins (desmoplakins)
Hemidesmosome Increased stability of epithelia on extracellular matrix (ECM) Link intermediate filaments in the cell to the ECM through integrins rather than cadherins
Communicating Gap junction (nexus) Selective communication in the form of diffusible molecules between 1 and 1.5 kD Connexons in hexameric arrangement with central pores in adjacent cells lined up
41.
In Marfan syndrome, there
are mutations in the fibrillin gene resulting in abnormal structure. Which of
the following organs would you expect to be most affected?
Correct Answer
C. Aorta
Explanation
The aorta is the most affected organ because of the extensive elastin in the wall, and dissecting aortic aneurysms are common in these patients. Marfan syndrome is an autosomal dominant disease in which persons develop abnormal elastic tissue. Malformations include cardiovascular (valve problems as well as aortic aneurysm), skeletal (abnormal height and severe chest deformities), and ocular systems. The molecular basis of the disease is a mutation in the fibrillin gene. The lens is also often affected in patients with Marfan syndrome. The result is the dislocation of the lens because of loss of elasticity in the suspensory ligament.
42.
In Alport's syndrome, there
is a defect in the 5 chain of type IV collagen. One
would expect to see which of the following symptoms?
Correct Answer
B. Hematuria
Explanation
Alport's syndrome results in hematuria from the loss of the normal filtering properties of the glomerular basement membrane, leading to nephritis and eventually renal failure. Alport's is an X-linked syndrome in which there is an absence of the alpha 5(IV) chain, resulting in thickening of the basement membrane with splitting of the lamina densa. The basement membrane is composed primarily of type IV collagen, heparan sulfate proteoglycan, laminin, and entactin. Basement membranes are usually composed of an electron-lucent layer (lamina rara) closest to the epithelial layer and the electron-dense layer (lamina densa) below the lamina rara. Type IV collagen is found in the lamina densa of the basement membrane.
43.
Which of the following is the principal
proteoglycan with which collagen type IV interacts?
Correct Answer
D. Heparan sulfate
Explanation
Heparan sulfate is primarily associated with type IV collagen in basal laminae. Proteoglycans are large molecules that maintain hydration space in the extracellular matrix. They are composed of glycosaminoglycans such as chondroitin sulfate, dermatan sulfate, heparan sulfate, heparin, and keratan sulfate. Glycosaminoglycans are covalently linked to core proteins to form proteoglycans. The notable exception is hyaluronic acid, which forms the core of proteoglycan aggregates produced by the interaction between proteoglycan subunits and hyaluronic acid. Dermatan sulfate is found predominantly in the skin, blood vessels, and heart. Fibronectin is a fibrillar protein, whereas laminin and entactin are structural glycoproteins found in the extracellular matrix.
44.
Which of the following is
necessary for successful tumor metastasis?
Correct Answer
E. Cell-cell recognition at the site of new metastasis
Explanation
Tumor metastasis involves cell-cell recognition as the migrating cells establish a new tumor site, migration, and differentiation. Tumor cells are initially released from adhesion to each other and to the extracellular matrix. Dissolution of basement membrane is required for release of tumor cells from the source and passage through connective tissues and between endothelial cells of the blood or lymphatic vessels. Collagenases and other extracellular proteases are involved in this process. At the site of a new metastasis, there is a reestablishment of cell-cell and cell-matrix interactions. Very few of the tumor cells released into the bloodstream have metastatic capability or are successful in the production of a tumor at a new site.
45.
Degradation of the extracellular matrix is
accomplished by which of the following?
Correct Answer
B. Plasmin
Explanation
The extracellular matrix is degraded by plasmin, a protease. It solubilizes fibrin clots and degrades protein fibrinogen and a few coagulation factors. There are two groups of proteases: metalloproteases and serine proteases. Collagenase is one of the metalloproteases. Urokinase-type plasminogen activator (U-PA), a serine protease, converts the inactive molecule plasminogen to the active protease plasmin. Inhibitors of metalloproteases (TIMPs) and serpins are responsible for the inactivation of metalloproteases and serine proteases. Lysyl oxidase is involved in the cross-linking of collagen during synthesis.
46.
Which of the following
symptoms is most likely to result from systemic mastocytosis?
Correct Answer
D. Hepatic fibrosis
Explanation
Periportal fibrosis of the liver often occurs in systemic mastocytosis due to the extensive infiltration of mast cells into the liver. Mastocytosis is a disease in which there is an excessive production of mast cells by the bone marrow. The result is an excessive release of the bioactive products contained in mast cell granules: histamine, heparin, eosinophil chemotactic factor of anaphylaxis (ECF-A), slow-reacting substance of anaphylaxis (SRS-A), and leukotrienes. Excessive production of acid by the parietal cells of the stomach occurs because of the overstimulation of histamine receptors on these cells. This can result in peptic ulcers and gastritis. Mastocytosis also induces urticaria pigmentosa, including edema (caused by the increased vascular permeability induced by histamine and SRS-A) and infiltration of eosinophils (attracted by ECF-A), which causes itching. Lower gastrointestinal tract symptoms include increased motility and diarrhea due to the stimulation by mast cell contents.
47.
Wound healing in the skin is
mediated by various cytokines and growth factors and results in a series of
repair steps. Platelet-derived growth factor (PDGF) is being used effectively
to treat poorly healing wounds. Increased levels of PDGF will do which of the
following?
Correct Answer
E. Stimulate proliferation of vascular smooth muscle
Explanation
Platelet-derived growth factor (PDGF) stimulates proliferation of vascular smooth muscle cells to facilitate blood vessel repair. Wound healing is a complex process initiated by damage to capillaries in the dermis. The clot forms through the interaction of integrins on the surface of blood platelets with fibrinogen and fibronectin. Fibrin is the primary protein that constructs the three-dimensional structure of the clot. Macrophages and fibroblasts are attracted by platelet-derived growth factor (PDGF). In addition to its effect on vascular smooth muscle, PDGF also stimulates proliferation of fibroblasts and extracellular matrix protein synthesis by fibroblasts at the wound site. A scar is formed as a very dense region of type I collagen fibers. Macrophages remove debris at the wound site and are also involved in the remodeling of the scar.
48.
Reticular fibers in lymphoid
organs are comprised of which collagen?
Correct Answer
B. Collagen type III
Explanation
The reticular fibers form the support for lymphoid organs such as the spleen, bone marrow, and lymph nodes and are composed of type III collagen.
Collagen is a family of extracellular matrix proteins, all of which contain three chains that vary in structure. There are about 20 defined types. The most important of these are summarized in the table below.
Type Location Function and Other Information
I General C.T., bone, and fibrocartilage Most abundant type of collagen, 67-nm periodicity, tensile strength
II Hyaline and elastic cartilage Thinner fibrils than type I, tensile strength, electrostatic interactions between type II collagen and proteoglycan aggregates form the molecular basis for the rigidity of hyaline cartilage
III Spleen, bone marrow, and lymph nodes Reticular framework, stains with silver
IV Basement membrane Filtration, support, meshwork scaffolding, interacts with heparan sulfate proteoglycan to produce a polyanionic change distribution that facilitates selective filtration; synthesized by epithelia; it retains propeptides that are used to form a meshwork; also interacts with fibronectin
V Placental basement membrane, muscle basal lamina Linkage function in basement membrane(?)
VII Basement membrane of skin and amnion Anchoring fibers
VIII Endothelium Unknown function
IX–XII Cartilage Fibril-associated collagens with interrupted triple helices (FACIT) regulate orientation and function of fibrillar collagens
49.
Collagen
The cells labeled with the arrows in the figure
synthesize which of the following?
Correct Answer
D. IgE
Explanation
The cells delineated by the arrows in the photomicrograph are plasma cells that are responsible for immunoglobulin (antibody) production. Plasma cells produce all the immunoglobulins: IgG, IgA, IgM, IgD, and IgE and are derived from B lymphocytes. The differentiation of plasma cells requires macrophages (antigen-presenting cells), which phagocytose and present antigen + MHC II and T-helper cells. Plasma cells are characterized by eccentric nuclei with coarse granules of heterochromatin arranged in a radial pattern about the nuclear envelope. Membrane-bound ribosomes are extremely plentiful, providing the cytoplasm with a characteristic intense basophilia. The ribosomes are involved in antibody production, principally immunoglobulin G (IgG). The juxtanuclear region, which does not stain, represents the Golgi complex, in which the antibodies are processed for secretion. The function and origin of the connective tissue cells is summarized in the table below.
Cell Type Origin Function
Fibroblast Mesenchyme Synthesis of fiber (collagen, elastic, reticular) and ground substance (proteoglycans and glycoproteins of connective tissue matrix
Macrophages (e.g., Kupffer cells, Langerhans cells and microglia) Monocyte (bone marrow) Phagocytosis, antigen presentation, produce and respond to cytokines.
Lymphocytes T lymphocytes Bone marrow (thymus-educated) Cell-mediated immunity (CD8+) and helper T cells (CD4+)
B lymphocytes Bone marrow (bone marrow-educated) Humoral immunity
Plasma cell B lymphocyte Immunoglobulin secretion
Neutrophils (PMNs) Bone marrow First cells to enter an inflammation site, secrete myeloperoidase, phagocytose bacteria, and die (forming pus)
Eosinophils Bone marrow Source of major basic protein, histaminase (breakdown of histamine), arylsulfatases (degradation of leukotrienes), phagocytosis of antigen-antibody complexes and parasites
Basophils Bone marrow (different stem cell from mast cell) Blood source of histamine
Mast cells connective tissue mast cells (CTMC) and mucosal mast cells (MMC) Bone marrow CTMC are T-lymphocyte independent, MMC are T-lymphocyte dependent, secrete histamine and slow-reacting substance of anaphylaxis [(SRS-A) increase vascular permeability], heparin (anticoagulant), eosinophil chemoattractant factor of anaphylaxis [(ECF-A), chemoattraction of eosinophils], leukotrienes (smooth muscle contraction)
50.
The cells delineated by the box in the light
micrograph of a developing long bone synthesize which of the following?
Correct Answer
C. Alkaline pHospHatase
Explanation
The light micrograph illustrates a developing long bone. The zone shown is the region of chondrocyte hypertrophy and the cells synthesize alkaline phosphatase, which calcifies the cartilage matrix. This secretion results in the eventual death of these cells that depend on diffusion to obtain oxygen and nutrients from the matrix. During development of the long bones of the body, specific zones are established as a cartilage model of a long bone is converted to mature bone. The zones from the epiphysis toward the center of the shaft (diaphysis) are as follows: resting zone, proliferative zone, hypertrophy zone, and zone of calcified cartilage that is used as the scaffolding for the deposition of bone. The periosteal bud represents the ingrowth of blood vessels (angiogenesis), bone marrow, and osteoprogenitor cells into the diaphysis. The angiogenesis is required for bone formation. Bone is formed by the action of osteoblasts forming type I collagen, noncollagenous proteins (e.g., osteocalcin, osteopontin, and osteonectin), and alkaline phosphatase, which plays an essential role in mineralization of the osteoid. Cyclins are synthesized by cells passing through the cell cycle (cells in the proliferative zone), acid phosphatase is synthesized by osteoclasts, and type I collagen and osteocalcin are sythesized by osteoblasts.