Epithelial Tissue

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An 11 month old girl is referred to a pediatric gastroenterology clinic due to a history of generalized weakness, slow growth and diarrhea. For the past month she has been hospitalized regularly to receive parenteral nutrition. Examination of the epithelium lining her small intestine confirms that the failure to absorb nutrients is most likely due to a significant decrease in which of the following A. Microvilli B. Gap junctions C. Cilia D. Cell layers E. Basement membrane thickness

*The answer is A*. Microvilli assist in reabsorption.

Which one of the following is a tumor arising from glandular epithelium? (A) Adenocarcinoma (B) Bullous pemphigoid (C) Carcinoma (D) Edema (E) Immotile cilia syndrome

*The answer is A.* Adenocarcinomas are epithelial tumors that originate in glandular epithelia. Carcinomas originate from surface epithelia.

A 68-year-old woman presents with a breast lump that she discovered 5 days ago. A biopsy reveals ductal carcinoma. Immunohistochemical assays are performed to investigate the role of cell adhesion molecules in malignancy. In contrast to normal ductal epithelial cells, this patient's cancer cells exhibit decreased expression of a cell adhesion protein (absence of brown stain indicated by the asterisk, shown in the image). Which of the following cell adhesion proteins was most likely down-regulated in this patient's ductal carcinoma? (A) Cadherin (B) Fibronectin (C) Integrin (D) Laminin (E) Selectin

*The answer is A.* Cadherins are a family of calcium-dependent cell adhesion proteins. They form "zipper-like" anchoring junctions at the cell surface that mediate cell adhesion and transmembrane signaling. A variety of studies have shown that E-cadherin gene expression is reduced in most epithelial cancers (carcinomas). Without E-cadherin, neoplastic cells undergo an epithelial-mesenchymal transition, penetrate basement membranes, and invade capillary/lymphatic channels. Up-regulation of cadherin gene expression has been shown to suppress the invasion and metastasis of malignant cells. Fibronectin and laminin (choices B and D) are extracellular matrix glycoproteins. Integrins (choice C) mediate cell-substrate adhesion. P-selectin mediates the attachment of neutrophils to activated endothelial cells during acute inflammation.

The distribution of organelles in cultured endothelial cells is examined using immunocytochemical techniques. A peripheral web of filamentous proteins is identified by confocal fluorescence microscopy (arrowhead, shown in the image). This web consists primarily of which of the following filamentous proteins? (A) Actin (B) Desmin (C) Lamin (D) Nestin (E) Tubulin

*The answer is A.* Cytoskeletal proteins include microtubules (composed of tubulin), microfilaments (composed of actin), and intermediate filaments (composed of tissue-specific filamentous proteins). Actin filaments are found in most cells. In epithelial cells and tissues, actin filaments organize microvilli and regulate changes in cell shape and cell locomotion. In many lining epithelial cells, actin filaments form a dense terminal web that stabilizes the apical membrane domain (including microvilli). Lamins (choice C) are intermediate filament proteins that organize nuclear chromatin. Tubulins (choice E) form microtubules that regulate vesicle transport and cell division. Desmin and nestin (choices B and D) are intermediate filament proteins expressed by muscle cells and neural stem cells, respectively.

A 42-year-old woman of Mediterranean descent presents with multiple oral blisters and a few cutaneous blisters on her back and buttocks. The superficial bullae are fragile, some have unroofed to form ulcerated lesions, and there is a positive Nikolsky sign. Blood tests reveal antibodies to a subfamily of cadherins and immunohistochemical staining of a biopsy from the oral mucosa shows distribution of the antigen throughout the epithelium. In what structures is the defect that is causing this patient's condition? a. Desmosomes b. Tight junctions c. Hemidesmosomes d. Gap junctions e. Reticular lamina

*The answer is A.* Desmosomes a type of intercellular junction in animal cells that functions as a rivet, fastening cells together. The major transmembrane link proteins in desmosomes is the cadherin family, which consists of desmoglein and desmocollin.

You are investigating the role of cell adhesion molecules in embryonic development. Sections of a gastrula-stage mouse embryo are stained with periodic acid-Schiff reagent and counterstained with methylene blue. Which of the following families of proteins forms anchoring junctions between adjacent epithelial cells in the neural ectoderm of this embryo (arrow, shown in the image)? (A) Cadherins (B) Cloudins (C) Integrins (D) Occludins (E) Selectins

*The answer is A.* During gastrulation, epiblast cells invaginate along the primitive streak to form mesodermal cells that migrate between the epiblast and the hypoblast. Cells that remain in the epiblast layer form the presumptive neural plate. This epithelial tissue is characterized by the presence of anchoring junctions that bind cells together and organize cytoskeletal proteins. Anchoring junctions include (1) zonula adherens junctions (cadherins linked to actin microfilaments) and (2) macula adherens junctions (cadherins linked to intermediate filaments). Cadherins are a family of calcium-dependent proteins that mediate cell adhesion, cell migration, and transmembrane signaling. Cadherins mediate epithelial cell-cell adhesion by forming "zipper-like" molecular interactions at the cell surface. Cloudins and occludins (choices B and D) form tight junctions (zonula occludens). Integrins (choice C) mediate cell-substrate adhesion at sites of focal adhesions and hemidesmosomes. Selectins (choice E) mediate leukocyte margination and extravasation during inflammation.

Which one of the following statements about epithelia is true? (A) They are polarized. (B) They are vascular. (C) They are completely surrounded by a basal lamina. (D) They contain wide intercellular spaces. (E) They are not part of the wall of blood vessels.

*The answer is A.* Epithelia are polarized, meaning they show sidedness and have apical and basolateral surfaces with specific functions.

Dysplasia in a stratified epithelium would be indicated by observing which feature of some of the cells above the basal layer? A. They are dividing B. They are squamous C. They contain desmosomes D. They contain keratin filaments E. They contain nuclei

*The answer is A.* Epithelial cells normally require contact with the basal lamina in order to divide. The other features listed can all be found in normal epithelia.

You attend a lecture on the physiology of lactation and breast-feeding. Under the influence of pregnancy-associated hormones, epithelial cells of the mammary gland secrete lipids, carbohydrates, and proteins. The lipid components of breast milk are released from the apical surface of the glandular epithelial cells as a lipid droplet within an envelope of the plasma membrane. Which of the following terms best describes this mechanism of secretion? (A) Apocrine (B) Eccrine (C) Endocrine (D) Holocrine (E) Merocrine

*The answer is A.* Exocrine glands use different mechanisms for secreting their products. These mechanisms are described as (1) apocrine (budding of apical cytoplasm); (2) merocrine (choice E, fusion of membrane-bound secretory vesicles with the plasma membrane); and (3) holocrine (choice D, release of a cellular inclusion following programmed cell death). Eccrine (choice B) refers to the secretion of water and salt by dermal sweat glands. Endocrine secretion (choice C) also involves the fusion of secretory vesicles with the plasma membrane (merocrine secretion). However, endocrine glands are ductless glands that release hormones directly into the circulatory system.

An 11-month-old girl is referred to a pediatric gastroenterology clinic due to a history of generalized weakness, slow growth, and refractory diarrhea. For the past month she has been hospitalized regularly to receive parenteral nutrition. Examination of the epithelium lining her small intestine confirms that the failure to absorb nutrients is most likely due to a significant decrease in which of the following? a. Microvilli b. Gap junctions c. Cilia d. Cell layers e. Basement membrane thickness

*The answer is A.* Microvilli are actin-based fingerlike extensions of plasma membrane of apical epithelial cells, which increase surface area for absorption

An individual genetically unable to synthesize normal occludin is likely to have epithelia with defective regulation in which of the following? a. Material crossing the epithelium between the cells (paracellular movement) b. Communication between the cells c. Attachment to the basement membrane d. Strong attachment to neighboring cells e. Movement of membrane proteins in the apical domains of cells

*The answer is A.* Occludins are proteins found in tight junctions. Tight junctions control the passage of molecules between adjacent cells.

A sample of the epididymis, collected at autopsy, is examined by light microscopy in the pathology department. The nuclei of sperm are visible within the lumen of the duct. Epithelial cells lining the epididymis exhibit long stereocilia (shown in the image). Which of the following proteins determines the shape and size of these specialized apical membrane structures? (A) Actin (B) Desmin (C) Keratin (D) Tubulin (E) Vimentin

*The answer is A.* Stereocilia are found only in the epididymis and on certain sensory cells of the inner ear. Despite their name, these apical membrane structures are really long, immotile microvilli. Like microvilli, stereocilia are filled with organized bundles of actin filaments. In the epididymis, stereocilia provide increased surface area for absorption of fluid. In the inner ear, these delicate structures serve as exquisitely sensitive mechanoreceptors. Tubulin (choice D) organizes cilia. Desmin, keratin, and vimentin (choices B, C, and E) are intermediate filament proteins.

Epithelial cells line the gastrointestinal tract, respiratory tree, cardiovascular system, and genitourinary system and cover the skin. Which of the following cellular properties best distinguishes lining/coating epithelial cells from other cells/tissues in the body? (A) Apical and basal membrane domains (B) Cell-cell anchoring junctions (C) Cell-extracellular matrix anchoring junctions (D) Communicating (gap) junctions (E) Pericellular lamina externa

*The answer is A.* The body is woven together with aggregates of cells (tissues) that collaborate to serve a common function. These tissue functions include (1) protection, transport, and secretion (epithelial tissue); (2) contraction and movement (muscle tissue); (3) reception and transmission of information (neural tissue); and (4) support (connective tissue). Epithelial tissue is divided into two general types based on function, namely lining/coating and glandular. Lining or coating epithelium is further classified on the basis of morphology (e.g., simple or stratified). In addition to absorption, secretion, and protection, epithelial cells provide receptors for the special sense organs. *Lining/coating epithelial cells exhibit polarity. They have distinct apical and basal membrane domains*; they feature close apposition of lateral membrane borders; and they synthesize a basal lamina that provides attachment and structural support. None of the other cellular features is unique to epithelial cells. Most cells/tissues feature anchoring and communicating cell junctions. Adipocytes, nerves, and muscle cells secrete a pericellular matrix that is referred to as lamina externa (choice E).

A section of trachea obtained at autopsy is stained with H&E and examined at high magnification (shown in the image). Identify the type of the lining epithelium. (A) Ciliated pseudostratified columnar with goblet cells (B) Glandular epithelium (C) Keratinized stratified squamous (D) Nonkeratinized stratified squamous (E) Simple columnar with goblet cells

*The answer is A.* This image illustrates histologic features of the "respiratory epithelium" that lines the conducting airways of the lungs. Careful examination of this section of the trachea reveals (1) ciliated columnar epithelial cells, (2) distinct sizes/shapes of cell nuclei within the epithelium, and (3) numerous large secretory cells (goblet cells). Cilia are specialized apical membrane organelles that beat in a whiplike fashion to remove mucus and inhaled particles from the lungs. They function as a "mucociliary ladder." The distinct populations of cell nuclei shown in the image suggest that there are distinct populations of cells within the epithelium. If these cells are layered, then the epithelium is stratified. On the other hand, if these cells make contact with the underlying basement membrane, then the epithelium is said to be "pseudostratified." Although it is difficult to demonstrate by light microscopy, respiratory epithelium is pseudostratified. The basal membrane domains of all cells in the epithelium are attached to the common basement membrane. Goblet cells secrete a protective mucus. None of the other types of epithelium describes the distinct histologic features of respiratory epithelium.

A 58-year-old man presents with a pigmented skin lesion on the lateral aspect of his right leg. A punch biopsy of the skin lesion is examined by light microscopy. Which of the following types of epithelium describes the patient's epidermis (indicated by the double arrow, shown in the image)? (A) Keratinized stratified squamous (B) Nonkeratinized stratified squamous (C) Pseudostratified columnar (D) Stratified cuboidal (E) Transitional

*The answer is A.* This patient's skin biopsy shows a stratified epithelium composed of multiple cell layers. The superficial layer of this stratified epithelium features squamous cells that have undergone programmed cell death. As they undergo apoptosis, the keratinocytes leave behind an insoluble layer of keratin intermediate filament proteins (eosinophilic layer, visible in the image). None of the other types of epithelium describes histologic features of the epidermis.

Which one of the following is an autoimmune disease? (A) Adenocarcinoma (B) Bullous pemphigoid (C) Carcinoma (D) First-degree burn (E) Immotile cilia syndrome

*The answer is B.* Bullous pemphigoid is an autoimmune disease. Affected individuals form antibodies against their own hemidesmosomes

With a 5-year history of chronic respiratory infections, a year-old, non-smoking man is referred to an otolaryngologist. A bronchial biopsy indicates altered structures in the epithelial cells. Which of the following, if altered to reduce function, is most likely involved in this patient's condition? a. Hemidesmosomes b. Cilia c. Basolateral cell membrane folds d. Microvilli e. Tight junctions

*The answer is B.* Cilia are microtubule-based hairlike projections that extend from the plasma membrane and are used for locomotion. This can be found in the respiratory tract.

Which of the following cellular features is used in naming types of epithelia? a. Shape of cells in the basal layer b. Number of cell layers c. Presence of a basal lamina d. Size of the nuclei e. Nature of the cell junctions that are present

*The answer is B.* Epithelial cells are named based on the number of cell layers. For example, simple epithelium has one layer and stratified epithelium has two or more layers.

In addition to collagen and proteoglycan, the basal lamina of the epithelial cells identified in the image consist of which of the following structural proteins? (A) Desmoplakin (B) Laminin (C) Talin (D) Vimentin (E) Vinculin

*The answer is B.* Epithelial cells secrete an adhesive matrix of glycoproteins and proteoglycans along their basal membrane. This pericellular basal lamina provides support and links epithelial cells to the underlying connective tissue. Basal laminae and connective tissue collagen fibers (joined together) form basement membranes that are visible in some tissues. Molecular components of the basal lamina include laminin, entactin, nidogen, type IV collagen, and proteoglycans (e.g., heparan sulfate). Assembly of the basal lamina is initiated by the attachment of integrin membrane receptors to laminin in the pericellular matrix. Entactin and nidogen form connections between laminin and type IV collagen. In addition to providing structural support, basal laminae sequester signaling molecules that regulate epithelial cell growth and differentiation. Desmoplakin, talin, and vinculin (choices A, C, and E) are attachment proteins that interact with cadherin and/or integrin receptors to form cell-cell anchoring junctions. Vimentin (choice D) is an intermediatefilament protein.

Organs of the anterior neck are examined by a double-headed microscope. The pathology resident asks you to describe the small, tightly packed cells with central nuclei (shown in the image). These cells exhibit which of the following patterns of epithelial cell differentiation? (A) Complex stratified (B) Glandular (C) Pseudostratified (D) Simple squamous (E) Stratified cuboidal

*The answer is B.* Epithelial tissue can be broadly classified as lining/coating or glandular. This autopsy specimen reveals glandular tissue in the parathyroid gland. The epithelial cells are small, monomorphic, and tightly packed with indistinct cell boarders. They secrete parathyroid hormone, which is taken up by capillaries to enter the systemic circulation. In contrast to lining/coating epithelial cells, these glandular epithelial cells appear to lack polarity. However, closer inspection reveals that these epithelial cells are organized into anastomosing cords and clusters. The endocrine cells are surrounded by adipocytes. The large clear spaces in these connective tissue cells are remnants of lipid inclusions that were extracted during tissue preparation. None of the other types of epithelium describes histologic features of the parathyroid gland.

A section of trachea obtained at autopsy is stained with H&E and examined at high magnification (shown in the image). Which of the following membrane junctions anchors the epithelial cells described above to extracellular matrix molecules in the underlying basal lamina? (A) Gap junctions (B) Hemidesmosomes (C) Macula adherens (D) Zonula adherens (E) Zonula occludens

*The answer is B.* Membrane junctions that anchor cells to the extracellular matrix include focal adhesions and hemidesmosomes. Focal adhesions link the extracellular matrix to intracellular actin bundles through integrin membrane receptors. Focal adhesions are dynamic structures that regulate changes in cell motility and differentiation. By contrast, hemidesmosomes provide stable connections between polarized epithelial cells and the underlying basal lamina. Hemidesmosomes link the extracellular matrix to intermediate filament proteins through integrin membrane receptors. The distinction between the basal lamina and basement membrane is often a point of confusion. Basal laminae are pericellular deposits of glycoproteins and proteoglycans that are secreted by epithelial cells. This layer is very thin and cannot be visualized by light microscopy. By contrast, basement membranes are thicker and may be visualized by light microscopy, particularly in sections that are stained for carbohydrate using periodic acid-Schiff (PAS). Basement membranes consist of two layers of extracellular matrix: (1) glycoproteins and proteoglycans of the basal lamina and (2) type III collagen (reticular) fibers secreted by connective tissue fibroblasts. None of the other membrane junctions anchors epithelial cells to the basal lamina.

Which one of the following statements about stratified squamous epithelium is true? (A) The surface layer of cells is always keratinized. (B) The cells in its most superficial layer are flattened. (C) Its basal cells rest on an elastic lamina. (D) Its cells lack desmosomes. (E) It lines the ducts of sweat glands.

*The answer is B.* Stratified squamous epithelium is characterized by flattened cells with or without nuclei in its superficial layer. It may or may not be keratinized, and it rests on a basal lamina produced by the epithelium. Stratified cuboidal epithelium lines the ducts in sweat glands.

A 10-year-old girl scrapes her elbow on the sidewalk while skateboarding. Physical examination reveals a 5-cm superficial skin abrasion. Which of the following cellular processes regulates regeneration of the epidermis in this patient's superficial abrasion? (A) Differentiation of myoepithelial cells and wound contraction (B) Loss of cell contact inhibition of growth and motility (C) Platelet activation and intravascular coagulation (D) Proliferation of capillary endothelial cells (angiogenesis) (E) Stimulation of fibroblasts to deposit a provisional extracellular matrix

*The answer is B.* Superficial abrasions of the skin heal by a process of regeneration. Regeneration involves epithelial cell proliferation and migration. In brief, maturation of the epidermis requires an intact layer of basal stem cells that are in direct contact with one another. If this contact is disrupted, basal cells at the margin of the wound become activated. They proliferate and close the wound through cell migration. When epithelial continuity is reestablished, cell migration and cell division cease, and normal epidermal maturation resumes. This mechanism of epithelial growth regulation is referred to as "contact inhibition of growth and motility." The epidermal basement membrane provides a crucial "road map" that guides basal stem cells during regeneration of the epithelium. The other choices describe responses to deep wounds that involve the formation of granulation tissue.

Functions of the basement membrane include which of the following? a. Contractility b. Molecular filtering c. Active ion transport d. Excitability e. Modification of secreted proteins

*The answer is B.* The basement membrane acts as a filter for substances reaching epithelial cells. It also provides structural support for epithelial cells and helps to attach epithelia to underlying connective tissue.

A biopsy from the tracheal lining reveals epithelium as seen in the image above. What is the core structure of the apical cell modification shown at the arrow? A. microfilament B. microtubule C. intermediate filament D. sterocilia E. desmosome

*The answer is B.* The image shows cilia, which is made of microtubules.

Your histology instructor reminds you that epithelial cells have membrane channels that permit ions and small signaling molecules to pass between adjacent cells. Which of the following proteins forms these intercellular (gap) junctions? (A) Cadherins (B) Connexins (C) Netrins (D) Perforins (E) Porins

*The answer is B.* The lateral membrane borders of epithelial cells contain a variety of integral and peripheral membrane proteins that mediate cell adhesion and cell communication. Communicating (gap) junctions are formed by the assembly of subunits of the connexin family of integral membrane proteins. Together, 12 connexin proteins join to form a pore (connexon) that provide ionic coupling between adjacent cells. Gap junctions permit the rapid exchange of ions, metabolites, and small signaling molecules between cells and throughout the epithelium. Gap junctions are present in most tissues of the body (from nerve to muscle). They help tissues share resources and coordinate functions. Cadherins (choice A) are calcium-dependent cell adhesion molecules. Netrins (choice C) are secreted proteins involved in axon guidance during development. Perforins (choice D) are cytolytic proteins produced by killer T lymphocytes. Porins (choice E) are channel proteins found in the outer membrane of gram-negative bacteria.

A 50-year-old man comes to the physician because of a cough productive of large quantities of mucus for 6 months. He has smoked 1 pack of cigarettes daily for 25 years. Which of the following cell types is the most likely cause of the increase in this patient's secretion of mucus? (A) Columnar ciliated epithelial cells (B) Goblet cells (C) Interstitial cells (D) Macrophages (E) Pneumocyte epithelial cells

*The answer is B.* The main role of goblet cells is to secrete mucus in order to protect the mucous membranes where they are found.

Digital slides illustrating various tissues are examined in the histology laboratory. Your instructor asks you to discuss the epithelium that lines the collecting ducts in the renal medulla (arrows, shown in the image). You examine the digital slide and identify a new visual field located near the tip of a renal papilla. The epithelium that lines these ducts (arrows, shown in the image) exhibits which of the following patterns of morphology? (A) Pseudostratified cuboidal (B) Simple columnar (C) Simple cuboidal (D) Simple squamous (E) Stratified columnar

*The answer is B.* This image shows a single layer of columnar epithelial cells lining a collecting duct. The cells are taller than they are wide. The nuclei are located near the base of the cells. Compared to cuboidal cells, columnar cells are generally believed to be more metabolically active. The apical cytoplasm of these columnar cells may be filled with organelles involved in fluid transport and/or secretion. In this H&E slide preparation, the cell nuclei are basophilic, whereas the cytoplasm is acidophilic. The red patches/smudges shown in the image represent clumps of hemolyzed red blood cells. None of the other types of epithelium describes the morphology of these urinary collecting ducts.

A 64-year-old man presents with a small mass on the inner surface of his lower lip. Biopsy of the mass reveals chronic inflammatory cells. As you examine the biopsy, you observe a large sweat duct surrounded by loose connective tissue (shown in the image). Identify the type of epithelium. (A) Pseudostratified columnar (B) Stratified columnar (C) Stratified cuboidal (D) Stratified squamous (E) Transitional

*The answer is B.* This image shows stratified columnar epithelium lining an excretory duct in the lip. The cell nuclei are aligned in two distinct rows. The cells facing the lumen are taller than they are wide, hence the classification of this epithelium as stratified columnar. The duct is supported by loose connective tissue. Stratified columnar epithelium is rarely encountered in histopathology. None of the other types of epithelial tissue describes the histologic features of this large excretory duct.

A section of an intestinal biopsy described is stained with periodic acid-Schiff (PAS) and examined at high magnification (shown in the image). Identify the type of epithelium. (A) Pseudostratified cuboidal (B) Simple columnar (C) Simple cuboidal (D) Simple squamous (E) Stratified columnar

*The answer is B.* This photomicrograph shows a linear array of cell nuclei in the simple columnar epithelium that lines the mucosa of the small intestine. The nuclei are monomorphic and located near the basal region of these epithelial cells. The nuclei contain primarily euchromatin, suggesting an active pattern of gene expression. This slide preparation also illustrates the delicate nature of the lamina propria (connective tissue) that supports the avascular epithelium. Oxygen and nutrients move by passive diffusion into the overlying epithelium from capillaries in the lamina propria. None of the other types of epithelium describes histologic features of the intestinal mucosa.

A portion of the upper esophagus, collected at autopsy, is fixed with formalin, embedded in paraffin, sectioned at 6 μm, stained with H&E, and examined by light microscopy (shown in the image). Identify the type of epithelium. (A) Keratinized stratified squamous (B) Nonkeratinized stratified squamous (C) Pseudostratified columnar (D) Stratified cuboidal (E) Transitional

*The answer is B.* This section of the esophagus reveals a stratified epithelium composed of multiple cell layers. Basal stem cells (arrowheads, shown in the image) undergo sequential changes in cell size, shape, nuclear morphology, and gene expression as they are pushed up toward the surface. The upper layer of this stratified epithelium is composed of squamous cells. This tissue is referred to as a nonkeratinized stratified squamous epithelium, because it *lacks an external coating of insoluble keratin protein*. Evidence of nuclear pyknosis (chromatin condensation) in the superficial region of this epithelium indicates that the keratinocytes are undergoing cellular senescence. None of the other types of epithelium describes histologic features of the esophageal mucosa.

The release of lipid droplets from cells is which type of secretion? a. Merocrine b. Serous c. Apocrine d. Mucous e. Holocrine

*The answer is C.* Apocrine secretion involves loss of membrane-enclosed apical cytoplasm, usually containing one or more lipid droplets. Apocrine secretion, along with merocrine secretion, is seen in mammary glands.

Which one of the following statements about cilia is true? (A) They possess a 9 0 configuration of microtubules. (B) They do not contain an axoneme. (C) They contain ciliary dynein arms. (D) They are nearly identical to centrioles. (E) They play a major function in absorption.

*The answer is C.* Cilia contain an axoneme with ciliary dynein arms extending unidirectionally from one member of each doublet. Ciliary dynein has ATPase activity, and when it splits ATP, the adjacent doublets slide past one another and the cilium moves. Microvilli, not cilia, function in absorption.

Using immunohistochemistry a population of cells is shown to be positive for the protein connexin. From this we can infer that the cells are connected by what type of junction? a. Tight (occluding) junctions b. Zonula adherens c. Gap junctions d. Hemidesmosomes e. Desmosomes (macula adherens)

*The answer is C.* Gap junctions have connexins, which allows the direct transfer of small molecules and ions from one cell to another.

A researcher is studying an epithelial cell line that forms a sheet of cells and resembles gut epithelium in culture. These cells contain a heat-sensitive mutation. In cultures grown at 34°C, a small amount of fluorescent dye injected into one cell quickly diffuses to neighboring cells. At 39°C, however, the dye remains only in the injected cell. Careful microscopic examination shows no differences between the sheets at either temperature. It would be reasonable to expect to find the mutation in genes coding for which of the following structures? A. Basal lamina B. Desmosomes C. Gap junctions D. Keratin filaments E. Microvilli

*The answer is C.* Gap junctions provide connections between cells that facilitate the movement of small molecules. These junctions allow the spread of signaling molecules across an epithelium and help coordinate cellular activities.

A patient is seen in clinic complaining of blisters that appear at the slightest touch of his skin. Histologic examination of a skin biopsy shows that at the sites of these blisters, the epithelium has completely lifted off its basement membrane but is otherwise intact. If an autoimmune condition is responsible for this condition, antibodies in the patient's blood might be found in which of the following structures? A. Gap junctions B. Desmosomes C. Hemidesmosomes D. Keratin filaments E. Zonula occludens

*The answer is C.* Hemidesmosomes attach the basal layer of skin epithelial cells to the basal lamina; therefore, if they were the target of the patient's autoantibodies, the entire epithelium would lift off, as described in the question. If the antibodies reacted against desmosomes, cells above the basal layer would separate. Keratin filaments are inside cells and would not be available for antibody binding.

A medical student who has chronic lower respiratory infections seeks the advice of an ear, nose, and throat specialist. A biopsy of the student's respiratory epithelium reveals alterations in certain epithelial structures. This patient is most likely to have abnormal (A) microvilli. (B) desmosomes. (C) cilia. (D) hemidesmosomes. (E) basal plasmalemma infoldings

*The answer is C.* Individuals with abnormal respiratory cilia commonly have recurrent respiratory infections if the cilia are unable to clear the respiratory epithelium of microorganisms, debris, and so forth. The student may have immotile cilia syndrome, which is caused by a genetic defect resulting in cilia with axonemes that lack ciliary dynein arms and thus are unable to beat.

Exocrine glands in which the acini all produce a secretion of heavily glycosylated, hydrophilic proteins are an example of which type of gland? a. Serous gland b. Mixed gland c. Mucous gland d. Tubuloacinar gland e. Simple gland

*The answer is C.* Mucous glands synthesize and release heavily glycosylated proteins called mucins.

You are investigating the role of cell adhesion molecules in embryonic development. Sections of a gastrula-stage mouse embryo are stained with periodic acid-Schiff reagent and counterstained with methylene blue. Further examination of the embryo described reveals fluid-filled cavities above and below the amnion (shown in the image). Which of the following proteins plays an important role in regulating fluid transport and cavity formation in this embryo? (A) Catalase (B) Cytochrome p450 (C) Na/K ATPase (D) Perforin (E) Superoxide dismutase

*The answer is C.* The amnion is a thin membrane sac that surrounds the embryo and fetus. It provides a protective, fluid filled environment that permits the embryo to fold properly and develop normal limb appendages. Epithelial cells in the embryo and adult express a variety of transport proteins and pumps that move fluid and electrolytes from one compartment to another. For example, Na/K ATPase is a membrane pump that regulates water transport (uptake) in the gastrointestinal tract and kidney. This integral membrane protein uses ATP to transport sodium across the plasma membrane. If the pump is restricted to the lateral/basal membrane of a polarized epithelial cell, then transport of sodium toward the underlying basal lamina will cause water to flow across the epithelium to maintain isosmotic balance. Water can also move in the opposite direction across an epithelium to form a fluid-filled cavity. None of the other proteins regulates fluid or electrolyte transport.

Which one of the following statements about the gap junction is true? (A) It extends as a zone around the apical perimeter of adjacent cells. (B) It possesses dense plaques composed in part of desmoplakins. (C) It permits the passage of ions from one cell to an adjacent cell. (D) Its adhesion is dependent upon calcium ions. (E) It possesses transmembrane linker glycoproteins.

*The answer is C.* The gap junction channel regulates the passage of ions and small molecules from cell to cell, excluding those having a molecular weight greater than 1,200 d. The tight junction is the zone of adhesion around the apical perimeter of adjacent cells. The other statements are characteristics of desmosomes.

A section of the submandibular gland is stained with H&E and examined in the histology laboratory (shown in the image). The secretory units indicated by the arrows are composed primarily of which of the following types of epithelial cells? (A) Endocrine (B) Goblet (C) Mucous (D) Paracrine (E) Serous

*The answer is C.* The submandibular gland is a mixed exocrine gland that features both serous and mucous secretory units (referred to as acini). Serous secretions are protein-rich and watery, whereas mucous secretions are carbohydrate-rich and viscous. The arrows shown on this image identify pale cells with compressed peripheral nuclei. The cells are clustered around a narrow central lumen. These epithelial cells secrete heavily glycosylated proteins (mucins) that do not take up H&E. They would, however, stain with periodic acid-Schiff. Goblet cells (choice B) are unicellular mucous glands found in the gastrointestinal tract. Paracrine cells (choice D) secrete signaling molecules (paracrine factors) that influence cells in close proximity. None of the other types of differentiated cells exhibit cytologic features of mucous cells in the submandibular gland.

Digital slides illustrating various tissues are examined in the histology laboratory. Your instructor asks you to discuss the epithelium that lines the collecting ducts in the renal medulla (arrows, shown in the image). Identify the type of epithelium. (A) Pseudostratified cuboidal (B) Simple columnar (C) Simple cuboidal (D) Simple squamous (E) Stratified columnar

*The answer is C.* This image shows parallel rows of cuboidal epithelial cells lining collecting ducts in the medulla of the kidney. The cells are more or less square (cuboidal) with central basophilic nuclei. The epithelial cells exhibit distinct polarity. Their apical membrane lines the lumen of the duct, whereas their basal membrane makes contact with a basal lamina of various adhesive glycoproteins. The basal lamina is not visible by light microscopy. The epithelium is said to be simple, because it is composed of a single layer (monolayer) of cells. Straight capillaries (vasa vecta) are observed to travel in parallel with the ducts. None of the other types of epithelium describes the morphology of these urinary collecting ducts.

A 58-year-old man presents with a pigmented skin lesion on the lateral aspect of his right leg. A punch biopsy of the skin lesion is examined by light microscopy. Further examination of the skin biopsy described reveals the ducts of sweat glands (arrows, shown in the image). Which of the following types of epithelium lines these excretory channels? (A) Pseudostratified columnar (B) Stratified columnar (C) Stratified cuboidal (D) Stratified squamous (E) Transitional

*The answer is C.* This image shows sweat ducts that are lined by a double layer of cuboidal epithelial cells. The cell nuclei are aligned in discrete rows. Tight (occluding) junctions between the ductal epithelial cells form an impermeable barrier. As a result of these zonula occludens junctions, the lateral membrane borders between adjacent ductal cells are not visible by light microscopy (shown in the image). Stratified cuboidal epithelium is rarely encountered in histopathology. It may reflect the need for greater support, or it may represent a transition zone for epithelial tissues that are switching from simple to stratified. None of the other types of epithelium describe histologic features of these sweat ducts in the dermis of the skin.

A 58-year-old woman with a history of diabetes complains of swelling of her ankles. Physical examination reveals edema of the lower extremities. A kidney biopsy is obtained. Which of the following histochemical stains can be used to highlight the patient's glomerular basement membrane when examined by light microscopy? (A) Aldehyde fuchsin (B) Hematoxylin and eosin (C) Luxol fast blue/cresyl violet (D) Periodic acid-Schiff (E) Trypan blue

*The answer is D.* Basement membranes can be visualized in tissues that are stained with periodic acid-Schiff. This histochemical reagent binds sugars that are abundant in basement membranes at the junction between epithelial cells and the underlying connective tissue. The glomerular basement membrane has been shown to contain an abundance of heparan sulfate proteoglycan. Diabetes mellitus, a complex metabolic disease associated with glucosuria and polyuria, is the leading cause of end-stage renal disease in the United States, accounting for a third of all patients with chronic renal failure. In this condition, the glomeruli show diffuse mesangial matrix expansion and thickening of the glomerular basement membrane. Diabetic glomerulosclerosis results in progressive renal failure. None of the other histochemical stains are particularly useful for visualizing basement membranes by light microscopy.

Which of the following proteins regulates the motility of cilia found along the apical membrane domain of columnar epithelial cells? (A) Actin (B) Desmin (C) Keratin (D) Tubulin (E) Vimentin

*The answer is D.* Cilia are amazing apical membrane extensions that serve a variety of functions including whiplike movement and signal transduction. Motile cilia generate a mucociliary ladder that removes inhaled particles from the lungs, whereas immotile cilia provide mechanoreceptors that monitor gravity and acceleration in the ear. Recently, cilia have been shown to generate tiny currents that regulate the development of left/ right asymmetry in the embryo. Without these "nodal cilia," the internal organs may be randomly placed. Cilia arise from membrane-associated microtubule-organizing centers, termed basal bodies. These organelles regulate the polymerization of αβ-tubulin dimers to form a core of microtubules that are referred to as the axoneme. In motile cilia, the axoneme is composed of a central pair of microtubules surrounded by nine microtubule doublets (9 + 2 configuration). Molecular motor proteins (e.g., dynein) hydrolyze ATP to initiate sliding movements of microtubules within the axoneme. Actin (choice A) polymerizes to form microfilaments. Desmin, keratin, and vimentin (choices B, C, and E) are intermediate filament proteins.

A biopsy of small intestine is examined at high magnification in the pathology department. Electron microscopic examination of the epithelial cells described reveals basolateral membrane infoldings (interdigitations). What is the most likely function of this membrane specialization? (A) Endocytosis (B) Enzyme secretion (C) Exocytosis (D) Fluid transport (E) Immune surveillance

*The answer is D.* Epithelial cells that line the gastrointestinal (GI) tract transport fluid from the lumen of the gut to the underlying connective tissue. This transcellular transport mechanism is facilitated by basolateral membrane infoldings that provide increased surface area for proteins that pump sodium outside the cell. Water from the lumen of the GI tract follows the sodium gradient that is established by these pumps. After leaving the cell, water and electrolytes are drained by postcapillary venules and lymphatic channels. Careful examination of the image provided reveals spaces between the basolateral membranes of the epithelial cells (arrowheads, shown in the image). These open spaces provide indirect evidence for fluid transport in this tissue. Basolateral membrane folds do not regulate the other cellular processes listed.

Which of the following is a condition affecting the epidermis of the skin in which blisters do not form? (A) Adenocarcinoma (B) Bullous pemphigoid (C) Carcinoma (D) First-degree burn (E) Immotile cilia syndrome

*The answer is D.* First-degree burns damage the upper layers of the epidermis only, and blisters do not form in the skin.

Pseudostratified epithelium lines which one of the following organs? A. duodenum B. bladder C. vagina D. trachea E. oviduct

*The answer is D.* Pseudostratified epithelium lines the trachea.

Which one of the following statements about glands is true? (A) Exocrine glands lack ducts. (B) Simple glands have ducts that branch. (C) Endocrine glands secrete into ducts. (D) Serous secretions are watery. (E) Holocrine glands release their contents by exocytosis.

*The answer is D.* Serous secretions produced by glands are often rich in enzymes and watery in consistency. Exocrine glands secrete into ducts and endocrine glands lack ducts. Merocrine glands use exocytosis to release their products.

A researcher was using reverse transcription polymerase chain reaction (RTPCR) to screen blood samples for carcinoma cells that had metastasized into the bloodstream of a patient. RT-PCR is a technique used for amplifying a defined sequence of RNA, and can provide a sensitive method of detecting a small number of cells that contain unique mRNAs in a tissue sample. Carcinomas are malignant tumors derived from epithelial cells. Blood can be considered as a specialized connective tissue. The researcher's RT-PCR primers should most likely be designed to amplify the mRNA encoding of which of the following proteins? A. Actin B. Collagen C. Elastin D. Keratin E. Vimentin

*The answer is D.* The only protein in the choices given that is specific for epithelial cells is keratin, making it the most likely target of the researcher's test. Specific keratins are expressed by carcinomas, and identifying these keratins is a useful tool for determining properties of cancer, such as the likely site of origin of metastatic tumors.

A biopsy of small intestine is examined at high magnification in the pathology department. Identify the apical membrane feature indicated by the arrows (shown in the image). (A) Basal lamina (B) Glycocalyx (C) Lamina propria (D) Striated brush border (E) Terminal web

*The answer is D.* This high magnification photomicrograph of the small intestine reveals epithelial cells that are specialized for absorption. The apical membranes of these enterocytes are packed with delicate, fingerlike projections (microvilli) that provide increased surface area for enzymes and transport proteins. These nonmotile organelles are lined by actin microfilaments. In H&E-stained slide preparations, microvilli appear as a striated (brush-like) border along the external surface of the lining epithelium. Basal laminae (choice A) are extracellular matrix deposits along the basal membrane. Glycocalyx (choice B) is a molecular coat of oligosaccharides along the external surface of the apical membrane. Lamina propria (choice C) is connective tissue that fills the core of the intestinal villi. The faint, eosinophilic line that runs parallel to the striated brush border is a terminal web of actin microfilaments (choice E).

A 50-year-old woman complains about a red papule on her right arm. Biopsy of the skin lesion reveals numerous, benign vascular channels filled with erythrocytes. The endothelial cells that line these vascular channels (arrows, shown in the image) exhibit which of the following patterns of epithelial tissue morphology? (A) Pseudostratified cuboidal (B) Simple columnar (C) Simple cuboidal (D) Simple squamous (E) Stratified columnar

*The answer is D.* This skin biopsy demonstrates vascular channels lined by thin cells with minimal cytoplasm and elongated nuclei. These flat scalelike cells form a simple squamous epithelium. Epithelial cells that line the heart, blood vessels, and lymphatic channels are referred to as endothelial cells. They have tight junctions that provide a permeability barrier between blood and extravascular tissues. In response to local injury, vascular endothelial cells initiate coagulation and inflammation. Mesothelium refers to the simple squamous epithelium that lines the pericardium, pleural cavities, and peritoneum. Hemangiomas are benign neoplasms of capillary endothelial cells. Erythrocytes within blood vessels can be used as a "histologic rulers," because they measure about 8 μm in diameter and their size is generally invariant. None of the other types of epithelium describes histologic features of vascular endothelial cells.

A 25-year-old woman spends an afternoon raking leaves. Later that evening, she discovers fluid-filled blisters on the palms of her hands. Leakage of fluid from dermal capillaries at sites of minor injury in the hands of this patient is regulated by changes in which of the following intercellular junctions? (A) Gap junctions (B) Hemidesmosomes (C) Macula adherens (desmosomes) (D) Zonula adherens (E) Zonula occludens

*The answer is E.* Capillary endothelial cells are characterized by the presence of tight junctions that establish a permeability barrier between blood and extravascular interstitial tissue. These occluding junctions (zonula occludens) bring the lipid bilayers of adjacent cells into close proximity. Zonula occludens are composed principally of three proteins: occludin, claudin, and junctional adhesion molecule. The extracellular portions of these transmembrane proteins form a zipper-like structure that seals the intercellular space and limits paracellular fluid transport. Parenthetically, transcellular transport occurs when biomolecules move across the plasma membrane. In response to injury (e.g., mechanical friction raking leaves), inflammatory cells release cytokines and signaling molecules (e.g., histamine) that trigger capillary endothelial cells to disassemble tight junctions and form intercellular gaps. These cellular changes lead to the leakage of fluid from the blood into the surrounding extravascular space (referred to as edema fluid). In some organs, capillary endothelial cells exhibit small windows (fenestrae) that facilitate the transport of biomolecules across the endothelium. None of the other intercellular junctions regulates vascular permeability.

Inherited defects in epithelial cell cilia function can result in human infertility; that is, sperm do not swim properly in males and eggs are not transported efficiently in females. A young couple arrives at an infertility clinic because they have not been able to conceive. Because these defects affect many epithelial cells throughout the body, the physician might be able to quickly identify the affected partner simply by asking each of them, "Which of the following symptoms do you experience?" A. Dry mouth B. Excessive bruising C. Fragile skin D. Frequent diarrhea E. Numerous colds

*The answer is E.* Cilia in the large airways of the lungs and the trachea sweep mucus up toward the oral cavity. The mucus traps pathogens that enter the respiratory system and provides an important defense against infection. Therefore, the partner who experiences numerous colds will most likely be the affected partner.

Which one of the following statements about the desmosome is true? (A) It is sometimes called a nexus. (B) It permits the passage of large proteins from one cell to an adjacent cell. (C) It has a plaque made up of many connexons. (D) It facilitates metabolic coupling between adjacent cells. (E) It is a disk-shaped adhesion site between epithelial cells.

*The answer is E.* Desmosomes are sites of adhesion characterized by dense cytoplasmic plaques and associated keratin filaments. Only gap junctions permit cell-to-cell communication of small molecules via their connexon channels.

Which of the following terms best describes the PAS-positive goblet cells identified in the image? (A) Multicellular endocrine glands (B) Multicellular exocrine mucous glands (C) Multicellular exocrine serous glands (D) Unicellular enteroendocrine glands (E) Unicellular exocrine mucous glands

*The answer is E.* Epithelial cells form glands that are specialized for the secretion of various molecules, including mucus, enzymes, saline solution, hormones, and other signaling molecules. These glands may be unicellular (e.g., goblet cells in the gastrointestinal tract) or multicellular (e.g., pancreas). Glands that secrete products onto a surface, either directly or indirectly via a communicating duct, are referred to as exocrine glands. By contrast, glands that lack a communicating duct system are referred to as endocrine glands. This image reveals scattered PAS-positive goblet cells in the jejunum of the small intestine. These secretory epithelial cells are best described as unicellular exocrine mucous glands. None of the other terms describes histologic features of intestinal goblet cells.

Mutations in human keratin genes K8 and K18 are associated with an increased susceptibility to several liver diseases. Intermediate filaments in liver epithelial cells expressing these mutant proteins show abnormal reorganization after the cells are stressed. Epithelial cells from the skin of these patients behave normally under all conditions. The most likely reason that skin epithelial cells behave normally is that the keratins in the epidermis are A. Not associated with desmosomes B. Not involved with mechanical stability C. Only expressed in the basal cell layer D. Only found in dead cells at the apical surface E. The product of genes other than K8 and K18

*The answer is E.* Humans express more than 50 keratin genes, so it is likely that epidermal cells express different keratins than those found in the liver; K8 and K18 are not highly expressed in skin.

Which one of the following is a hereditary disease that may be associated with infertility? (A) Adenocarcinoma (B) Bullous pemphigoid (C) Carcinoma (D) Edema (E) Immotile cilia syndrome

*The answer is E.* Immotile cilia syndrome results from a genetic defect that prevents synthesis of ciliary dynein ATPase, resulting in cilia that cannot actively move. Men are sterile because their sperm are not motile (the flagella in their tails lack this enzyme). Women may be infertile because cilia along their oviducts may fail to move oocytes toward the uterus.

In which type of epithelium are there some epithelial cells that are not directly lying on the basement membrane? A. simple squamous mesothelium B. simple squamous endothelium C. simple cuboidal epithelium D. pseudostratified columnar epithelium E. transitional epithelium

*The answer is E.* In transitional epithelium, the cells are stratified, which means that some cells are not in direct contact with the basement membrane. Whereas in simple epithelium, all of the epithelial cells are directly lying on the basement membrane.

An intermediate filament protein found in cytoplasm of most epithelial cells is which of the following? a. Actin b. Vimentin c. Laminin d. Myosin e. Keratin

*The answer is E.* Keratin is an intermediate filament found in the cytoplasm of most epithelial cells.

Epithelial cells that serve as integral elements of neural networks function as A. Ependymal cells B. Glial cells C. Interneurons D. Motor neurons E. Sensory receptors

*The answer is E.* Neuroepithelial cells, such as rods and cones, hair cells in the ear, and taste bud receptors in the mouth serve as sensory receptors for the nervous system.

A 58-year-old woman presents with painless hematuria (blood in her urine). Urine cultures are negative for E. coli. A biopsy of the urinary bladder is examined in the pathology department (shown in the image). Identify the type of epithelium. (A) Pseudostratified columnar (B) Stratified columnar (C) Stratified cuboidal (D) Stratified squamous (E) Transitional

*The answer is E.* The renal calyces, ureters, urinary bladder, and proximal urethra are lined by a transitional epithelium. This "urothelium" is *specialized to accommodate distention*. Urothelium is stratified and appears to consist of five or six cell layers when the bladder is empty (shown in the image). Upon distention, however, the same epithelium would appear to consist of only three layers. The superficial cells are typically described as being cuboidal and dome shaped, because they appear to bulge into the lumen. Hematuria may be a symptom of an ascending urinary tract infection or (less commonly) bladder cancer. None of the other types of epithelium describes histologic features of the bladder mucosa.

Transitional epithelium is characteristically found in the: A. ductus deferens B. gall bladder C. oviduct D. trachea E. ureter

*The answer is E.* Transitional epithelium is characteristically found in the ureter.


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