Integumentary System and Adipose Tissue

*The answer is A.* One of the major functions of the skin is to provide a water barrier to maintain water homeostasis. In addition to keratohyalin granules, keratinocytes in the stratum spinosum and granulosum produce small membrane-bounded granules with a lamellar core (so-called lamellar bodies). Lamellar bodies contain a mixture of hydrophobic barrier lipids that are released into pericellular spaces. These lipids are organized into wide sheets of multilayered structures. These wide sheets form an outer protective coating that is referred to as a lipid envelope. A thick layer of insoluble protein is also deposited on the inner surface of the keratinocyte plasma membrane. This intracellular structure is referred to as a cell envelope. Together, thick insoluble cell and lipid envelopes form an effective epidermal water barrier.

A 16-year-old girl on the high school athletic swim team is concerned about the effects of water on her skin. She asks you whether she should apply creams or lotions to waterproof her skin before entering the pool. You explain to her that the skin itself serves as an effective water barrier to protect the body. Which of the following components of the skin is most important in establishing an effective water barrier? (A) Cell and lipid envelopes (B) Desmosomes between keratinocytes (C) Thick epidermal basement membrane (D) Thick stratum corneum (E) Tight junctions between basal cells

*The answer is A.* The basal layer (stratum basale) is a single layer of basophilic cuboidal or columnar cells on the basement membrane at the dermal-epidermal junction. Hemidesmosomes in the basal cell membranes join these cells to the basal lamina, and desmosomes bind the cells of this layer together.

A 35-year-old female presented with a blister in the sole of her right feet. A skin biopsy was done and was reported that there was a separation of the epidermis from the dermis, what likely structure is disrupted? A. hemidesmosomes B. desmosomes C. fascia adherens D. tight junction E. gap junction

*The answer is C.* Langerhans cells are mononuclear phagocytes derived from bone marrow precursor cells. Monocytes in the bloodstream migrate into the epidermis where they differentiate into Langerhans dendritic cells. Langerhans cells are antigen-presenting cells in the epidermis. They phagocytose foreign substances that break through the skin barrier. Langerhans cells do not form zonula adherens junctions with neighboring keratinocytes. They move freely in the epidermis. Once an antigen is internalized, processed, and presented at the cell surface, Langerhans cells leave the epidermis and migrate to a regional lymph node. Here, Langerhans cells present foreign antigens to B and T lymphocytes (immunocytes). In routine H&E preparations, the nuclei of Langerhans cells stain intensely with hematoxylin, and the cytoplasm is clear. Keratinocytes (choices A, B, and E) are not involved in activating immune responses. Merkel cells (choice D) are mechanoreceptors in the skin.

A 48-year-old man complains of "poison ivy." Physical examination reveals skin rashes and blisters on his upper limb and trunk. Which of the following cells internalize and present "poison ivy" antigens to lymphatic cells of the immune system in this patient? (A) Basal cells (B) Granular keratinocytes (C) Langerhans cells (D) Merkel cells (E) Spinous keratinocytes

*The answer is C.* Hemidesmosomes are very small stud-like structures found in keratinocytes of the epidermis of skin that attach to the extracellular matrix (ECM).

A 52-year-old woman presents with severe blistering over her buttocks. Analysis of her serum demonstrates the presence of antibodies which by imunohistochemical techniques stain material located at the basement membrane of the epidermis in a biopsy of her skin. The underlying biological mechanism of her skin disorder involves an abnormality in which of the following structures? a. Macula adherens b. Gap junctions c. Hemidesmosomes d. Zonula occludens (tight junctions) e. Zonula adherens

*The answer is B.* Adipocytes produce the polypeptide hormone, angiotensinogen (AGE). This hormone is also secreted by other tissues/organs (e.g., liver). Over production of AGE is associated with systemic hypertension. For this reason, obese individuals commonly suffer from systemic hypertension. None of the other adipocyte-produced hormones regulates systemic blood pressure.

A 58-year-old obese man (BMI = 33 kg/m2) complains of headaches and blurry vision of 5-month duration. On physical examination, the blood pressure is 190/148 mm Hg. Malignant hypertension in this patient may be due, in part, to an increase in the serum concentration of which of the following adipocyte-produced hormones? (A) Adiponectin (B) Angiotensinogen (C) Estrogens (D) Leptin (E) Resistin

*The answer is C.* Adipocytes synthesize and secrete reticular (type III collagen) fibers that form an interwoven network that provides support. These reticular networks are only visible using special stains. They are invisible by H&E staining. The meshwork of polygonal strands seen in the image shown consists of the cytoplasm of two adjacent adipocytes and the thin layer of the extracellular matrix that is located between them. Rich supply of blood vessels and nerves are found in the extracellular spaces between the crowded adipocytes. Elastic fibers and collagen fibers are also present in the extracellular matrix between adipocytes, but unlike reticular fibers, they do not form an interwoven network. Skeletal and smooth muscle fibers (choices D and E) are not found in white adipose tissue.

The adipocytes in the image are surrounded and supported by a network that is composed chiefly of which of the following fibers? (A) Collagen (B) Elastic (C) Reticular (D) Skeletal muscle (E) Smooth muscle

*The answer is D.* Ichthyosis vulgaris is a relatively common, autosomal dominant genetic disease (afflicting 1/250). It is characterized by a striking thickening of the stratum corneum. Hyperkeratosis in the stratum corneum and reduced or absent keratohyalin granules are the characteristic pathologic features of this congenital disease. *Increased cohesiveness between keratinocytes causes scaling of the skin*. Although cosmetically disfiguring, this condition is not life threatening. None of the other mechanisms of disease describe the pathogenesis of ichthyosis vulgaris.

The parents of a 2-year-old girl are concerned about their daughter's white scaly skin. Physical examination reveals coarse, fish-like scales on the child's forearms. The patient's father is afflicted with the same condition (ichthyosis vulgaris). A skin biopsy from this child would most likely show which of the following histopathologic findings? (A) Accumulation of nucleated cells in the stratum corneum (B) Acute inflammation of the papillary dermis (C) Chronic inflammation of the reticular dermis (D) Excessive thickening of the stratum corneum (E) Hyperplasia of stem cells in the stratum basale

*The answer is C.* The stratum spinosum produces keratins and desmosomes different from those in the basale.

The stratum spinosum A. is found only in thick skin B. is one cell layer deep C. contains keratohyalin granules D. produces keratins and desmosomes different from those in the Basale

*The answer is B.* Chylomicrons are relatively large particles formed in the intestinal epithelial cells rich in ingested lipids.

What are the relatively large particles formed in the intestinal epithelial cells and rich in ingested lipids? a. Fatty acids b. Chylomicrons c. Glycerols d. Very-low-density lipoproteins e. Adipocytes

*The answer is B.* The circle on the micrograph encloses an eccrine sweat gland in the scalp. Eccrine glands release a watery product by merocrine secretion. Initially, the electrolyte balance of the fluid produced by the secretory cells is similar to blood plasma. However, almost all K+, Na+, and Cl- is resorbed by the ducts, thus sweat released on skin is hypotonic.

What is the composition of the secretion produced by the encircled structures on the micrograph when the secretion is released on the skin surface? A. Hypertonic relative to plasma B. Hypotonic relative to plasma C. Isotonic with plasma D. Viscous and odorless E. Viscous and waxy

*The answer is E.* Triglycerides are the most important form of lipid storage in both white and brown adipocytes.

What is the most important form of lipid storage in both white and brown adipocytes? a. Free fatty acids b. Cholesterol c. Chylomicrons d. Glycerol e. Triglycerides

*The answer is D.* The asterisk on the micrograph indicates an arrector pili muscle in the scalp. These muscles are bands of smooth muscle that originate in the connective tissue sheath of the hair follicle and attach to the papillary dermis. Contraction of an arrector pili muscle causes the hair follicle and shaft to become more vertical (piloerection), producing "goose bumps."

What is the predominant tissue in the structure shown in the micrograph indicated by an asterisk? A. Dense irregular connective tissue B. Dense regular connective tissue C. Nervous tissue D. Smooth muscle E. Striated muscle

*The answer is B.* Merkel's discs are found in the dermis of hairy skin and signal continuous touch.

Which of the following best describes an expanded tip tactile receptor found in the dermis of hairy skin that is specialized to detect continuously applied touch sensation? A) Free nerve endings B) Merkel's disc C) Pacinian corpuscle D) Ruffini's endings

*The answer is D.* Desmosomes provide sealant between adjacent cells in the epidermis.

Which of the following components of the epidermis provides sealant between adjacent cells? a. Keratohyaline granules b. Glycolipids and lipids c. Keratin d. Desmosomes e. Adherent junctions

*The answer is C.* The glassy membrane is a thickened basement membrane that separates the hair follicle from the dermis

Which of the following separates the hair follicle from the connective tissue of the dermis? a. External root sheath b. Internal root sheath c. Glassy membrane d. Hair cuticle e. Medulla

*The answer is C.* Eccrine sweat glands are simple, coiled tubular glands that have a duct lined by a stratified cuboidal epithelium. They are found in both thick and thin skin and are classified as merocrine glands, meaning they release only their secretory product, which does not include cells or portions of cells.

Which of the following statements about eccrine sweat glands is true? (A) They are absent in thick skin. (B) They are holocrine glands. (C) They have a narrow duct lined by a stratified cuboidal epithelium. (D) They secrete an oily material called sebum. (E) They empty into hair follicles.

*The answer is B.* Hair follicles are present only in thin skin. They are associated with sebaceous glands and arrector pili smooth muscle bundles.

Which of the following statements about hair follicles is true? (A) They are always associated with an eccrine sweat gland. (B) They are present in thin skin but not in thick skin. (C) Their associated arrector pili muscle is composed of striated fibers. (D) Their hair shaft inserts into the papillary layer of the epidermis. (E) They do not extend into the dermis.

*The answer is B.* Sebaceous glands produce sebum, an oily material, and release it into the upper shaft of the hair follicle by a mechanism called holocrine secretion (which means the product and cellular debris are both released from the gland).

Which of the following statements concerning sebaceous glands is true? (A) They do not begin to function until puberty. (B) They employ the mechanism of holocrine secretion. (C) They are present in thick skin. (D) They secrete only in response to hormones. (E) They produce a watery enzyme-rich secretion.

*The answer is E.* Merkel cells are found in the stratum basale.

A 64-year-old woman, who has always been proud of her suntanned, healthy look, is referred to a dermatologist with a blue violet, painless, 1.5-cm lump in the skin of her left shoulder. The lump is firm and cannot be moved, and has grown very rapidly over the past few weeks. The mass is removed surgically and the pathologist diagnoses it as a Merkel cell carcinoma. If the UV radiation to which her skin was exposed affected the Merkel cells, what other cell type sharing the same specific epidermal layer might also be affected? a. Fibroblasts of the papillary layer b. Keratinocytes of the stratum granulosum c. Cells of tactile (Meissner) corpuscles d. Keratinized epithelial cells e. Basal stem cells for keratinocytes

*The answer is A.* Arrector pili are small bundles of smooth muscle fibers extending from the midpoint of the external root sheath to the papillary dermis. Contraction of these muscles causes hair shafts to become erect resulting in the formation of tiny skin bumps (so-called goose bumps). Arrector pili muscle is innervated by sympathetic nerve fibers. Stresses such as cold and fear can stimulate contraction of these small muscles. None of the other cutaneous structures exhibit the distinctive histologic features of arrector pili muscle.

A section of thin skin is examined in the histology laboratory (shown in image). Identify the structure indicated by the arrows. (A) Arrector pili muscle (B) Collagen bundles (C) Connective tissue sheath (D) External root sheath (E) Glassy membrane

*The answer is E.* White adipose tissue cells do not increase in number during normal weight gain in the adult, they increase in size.

All the following are TRUE regarding white adipose tissue cells (adipocytes) EXCEPT A. they usually contain one large lipid droplet B. they are supported by a network rich in reticular fibers C. they can break down triglycerides into fatty acids D. they are stimulated by sympathetic nerves of the autonomic nervous system E. they increase in number during normal weight gain in the adult

*The answer is A.* In terms of adipocytes, multiocular refers to the large number of small cytoplasmic lipid droplets.

Applied to adipocytes, the term "multilocular" refers to which of the following? a. The large number of small cytoplasmic lipid droplets b. The proliferation of the cells in an obese individual c. The large number of mitochondria in the cells d. The high density of nerves supplying the tissue e. The type of mesenchymal cells also present

*The answer is A.* Dermal papilla refers to a tuft of vascularized loose connective tissue that is invaginated into the base of a hair bulb. A hair bulb (choice C) is the dilated proximal portion of a hair follicle. The dermal papilla is continuous with the surrounding dermal connective tissue and contains a capillary network that nourishes and sustains the living hair follicle. Disruption of this blood flow results in death of the hair follicle. Hair matrix (choice E) refers to the layer of epithelial cells covering the dermal papilla. External root sheath (choice B) is a continuation of the epidermis that covers the hair follicle (indicated by arrows in the image).

Examination of a specimen reveals a vertical section through a hair follicle (shown in the image). Identify the tuft of connective tissue demarcated by the dotted line. (A) Dermal papilla (B) External root sheath (C) Hair bulb (D) Hair follicle (E) Hair matrix

*The answer is C.* Fully differentiated white adipocytes are large cells, typically having diameters of 100 μm.

Fully differentiated white adipocytes are large cells, typically having diameters of approximately what size? a. 5 μm b. 10 μm c. 100 μm d. 500 μm e. 1000 μm

*The answer is D.* Holocrine secretion occurs in sebaceous glands.

Holocrine secretion occurs in A. gastric glands B. mammary glands C. sweat glands D. sebaceous glands

*The answer is D.* Important target cells of leptin are found in the hypothalamus.

Important target cells of leptin are found in which organ? a. Small intestine b. White adipose tissue c. Large intestine d. Hypothalamus e. Brown adipose tissue

*The answer is B.* A variety of hormones, growth factors, and cytokines are produced in white adipose tissue. Leptin (discussed earlier in this chapter) is a polypeptide hormone secreted by adipocytes that helps regulate food intake and body weight control. Therefore, adipose tissue is not only an organ for energy storage; it also serves as an endocrine organ. Adipose tissue does not regulate the other biological functions listed.

In addition to providing body insulation and maintaining energy homeostasis, adipose tissue is considered to be an important organ for which of the following biological functions? (A) Calcium storage (B) Endocrine secretion (C) Hematopoiesis (D) Immune surveillance (E) Wound healing

*The answer is D.* Observations with an electron microscope show that intercellular bridges are associated with desmosomes (maculae adherentes), linking the processes of adjacent cells in the stratum spinosum. Desmosomes also link cells within the other epidermal layers, but these cells do not form processes characteristic of bridges. The keratinocytes of the stratum basale also contain hemidesmosomes, which attach the cells to the underlying basal lamina.

Intercellular bridges are characteristic of which of the following layers of the epidermis? (A) Stratum granulosum (B) Stratum lucidum (C) Stratum corneum (D) Stratum spinosum (E) Stratum basale

*The answer is B.* Meissner corpuscles are encapsulated nerve endings present in dermal papillae, which are part of the papillary layer of the dermis. These corpuscles function as receptors for fine touch.

Meissner corpuscles are present in which of the following regions of the skin? (A) Dermal reticular layer (B) Dermal papillary layer (C) Hypodermis (D) Stratum basale (E) Epidermal ridges

*The answer is D.* Myoeptihelial cells aid in the secretory process by contracting to move the watery secretion into the duct.

Myoepithelial cells aid in the secretory process of which of the following? a. Melanocytes b. Sebaceous glands c. Keratinocytes of the granular layer d. Eccrine sweat glands e. Apocrine sweat glands

*The answer is D.* Pain receptors in the skin are free nerve endings.

Pain receptors in the skin are typically classified as which of the following? A) Encapsulated nerve endings B) Single class of morphologically specialized receptors C) Same type of receptor that detects position sense D) Free nerve endings

*The answer is C.* Stimulation of sympathetic nerves to brown fat would lead to increased heat production, intracellular cAMP, respiration, and uncoupling of oxidative phosphorylation.

Stimulation of sympathetic nerves to brown fat would lead to each of the following EXCEPT A. increased heat production B. increased intracellular cyclic AMP C. increased intracellular triglyceride D. increased respiration E. uncoupling of oxidative phosphorylation

*The answer is D.* Hormone-sensitive lipase acts on triglycerides to form free fatty acids and glycerol.

The hormone-sensitive lipase in the cells of adipose tissue acts primarily on what substrate? a. Glucose b. Free fatty acids c. Glycerol d. Triglycerides e. Very-low-density lipoproteins

*The answer is E.* The most significant factor in determining skin color is the content of melanin—a product of tyrosine metabolism. Melanocytes are neural crest-derived dendritic cells that are scattered among basal epidermal cells. They produce melanin within melanosomes and distribute these melanin granules to neighboring keratinocytes. The ratio of melanocytes to keratinocytes in the basal layer of the epidermis is referred to as the epidermal melanin unit. This ratio differs between different parts of the body but is essentially the same in all races. Skin color differences between the races are related primarily to the fate of melanin. In individuals with darker skin, the degradation of melanin within lysosomes proceeds at a slower rate than in light-skinned individuals. As a result of slower degradation in dark-skinned individuals, melanosomes are more widely distributed throughout the epidermis. As a result of faster degradation in light-skinned individuals, melanosomes are sparse in the upper layers of the epidermis. Increased number of melanocytes and increased synthesis of melanin (choices B and C) are biological responses to ultraviolet radiation. The other listed choices do not reflect variations in skin coloration.

You are invited to talk to elementary school students about your interest in biology and medicine. One of the students asks you to explain why his best friend has dark skin. Which of the following biological processes is responsible for darker pigmentation of the skin in those of African descent? (A) Decreased thickness of the stratum spinosum (B) Increased number of melanocytes (C) Increased production of melanin (D) Increased thickness of the stratum granulosum (E) Slower degradation of melanin

*The answer is A.* Sebaceous glands have holocrine secretion.

A 12-year-old boy is found to have systemic dysfunction of the sebaceous glands. Which type of secretion would be most affected in this patient? A. Holocrine B. Apocrine C. Paracrine D. Merocrine E. Eccrine

*The answer is C.* Birbeck granules are cytologic markers of Langerhans cells. By electron microscopy, these granules look like miniature tennis racquets. Malignant transformation of a Langerhans cell is referred to as Langerhans cell histiocytosis (LCH). LCH is a generic term for a group of rare diseases characterized by clonal proliferation of Langerhans cells. LCH includes three pathologic entities, namely, eosinophilic granuloma, Hand-Schüller-Christian disease, and Letterer-Siwe disease. A typical LCH lesion contains collections of abnormal Langerhans dendritic cells, as well as lymphocytes, eosinophils, and macrophages. LCH may occur anywhere in the body, ranging from isolated bone lesions to multisystem disease. None of the other cells exhibit intracellular Birbeck granules.

A 12-year-old boy complains of mild pain in his skull. Radiologic examination of the patient's skull reveals a large, lytic lesion in the occipital bone (shown in the image). Biopsy of the lytic lesion reveals collections of large, phagocytic cells with pale, eosinophilic cytoplasm. By electron microscopy, these large cells are discovered to have racquet-shaped intracellular structures known as "Birbeck granules." These granules are an ultrastructural feature of which of the following cells? (A) Fibroblasts (B) Keratinocytes (C) Langerhans cells (D) Lymphocytes (E) Osteoblasts

*The answer is B.* The region of the external root sheath near the insertion site of the arrector pili muscle and the origin of the sebaceous gland is referred to as the follicular bulge. This small structure is home to clusters of undifferentiated epithelial stem cells. Thus, the bulge region of the external root sheath is believed to serve as an epidermal stem cell (ES cell) niche. ES cells are multipotential stem cells that develop into components of the hair follicle (internal root sheath, cortex, medulla), as well as secretory cells lining the sebaceous glands. ES cells do not normally populate the stratum basale of the epidermis. However, when the epidermis is lost due to superficial abrasions or burns, ES cells migrate along the hair follicle glassy membrane toward the wound. Here, they proliferate and differentiate to resurface (regenerate) the skin lesion. The cellular and molecular signals that control ES cell differentiation and directed motility are important topics for basic research.

A 12-year-old girl suffers second-degree burns on her left arm while helping her father in the kitchen. Regenerative stem cells that migrate extensively to resurface this patient's skin wound originate from which of the following cutaneous structures? (A) Dermal papilla (B) External root sheath (C) Hair matrix (D) Internal root sheath (E) Stratum basale of epidermis

*The answer is D.* Acne vulgaris is chronic inflammation within obstructed sebaceous glands. It commonly occurs in individuals during or after puberty. Sebaceous gland secretions increase greatly at the time of puberty under the influence of circulating sex hormones. These hormonal changes also induce abnormal cornification of epithelial cells near the neck of the sebaceous glands. Together, (1) excessive production of sebum (secretory product of sebaceous glands) and (2) abnormal cornification lead to the dilation of the sebaceous follicle. This provides a rich environment for the growth of Propionibacterium acnes. This bacterium proliferates in the affected glands, leading to an intense chronic inflammatory response. None of the other cutaneous structures are related to the pathogenesis of acne.

A 15-year-old girl presents with severe acne. Physical examination reveals many discrete papules and pustules on her face and neck. Acne is a chronic inflammatory disorder that principally affects which of the following cutaneous structures? (A) Bulb of hair follicles (B) Capillary loops within papillary dermis (C) Dermal papillae of hair follicles (D) Sebaceous glands (E) Stratum basale of epidermis

*The answer is C.* EB simplex, also known as epidermolytic EB, is a group of autosomal dominant skin disorders. The blister in EB simplex is caused by lysis of individual keratinocytes. The lowermost portion of the basal cell cytoplasm separates from the upper portion of the cells. Small pieces of basal cell cytoplasm remain attached to the basement membrane and form the floor of the vesicle. A nearly intact epidermis forms the roof of the blister. EB simplex is caused by mutations in the genes that encode cytokeratins. Keratin intermediate filament proteins provide essential mechanical stability to keratinocytes. Bullous pemphigoid (choice A) and pemphigus vulgaris (choice D) are autoimmune blistering skin diseases that are caused by autoantibodies to normal skin proteins. Psoriasis (choice E) is a proliferative skin disease of unknown etiology. Patients with psoriasis do not present with oral mucosal blisters at birth.

A 2-day-old neonate cries violently whenever she is breast-fed. Physical examination of the neonate reveals numerous blisters in the oral mucosa and on the skin. Microscopic examination of a skin biopsy reveals separation between upper and lower portions of basal cells in the epidermis. The results of immuno-labeling assays are negative (i.e., they do not show evidence of immune complex deposition in the skin). Which of the following is the most likely diagnosis? (A) Bullous pemphigoid (B) Contact dermatitis (C) Epidermolysis bullosa simplex (D) Pemphigus vulgaris (E) Psoriasis

*The answer is D.* The arteriovenous anastomoses in the skin are referred as glomus bodies or AV shunts. The AV shunts serve as thermoregulators of the body. When AV shunts are open, blood flows directly from arterioles into venules and bypasses the capillary microcirculation. Numerous AV shunts are located in the dermis, between subcutaneous and subpapillary plexuses. In cold weather, the AV shunts open to decrease blood flow in the skin and thereby minimize heat loss. In warm/hot weather, the AV shunts close to increase blood flow through the capillary bed to facilitate heat loss. Together, AV shunts help maintain a constant body temperature.

A 4-year-old girl is rescued after becoming lost outdoors during a winter snowstorm. Physical examination indicates that the child is fine, except for exhaustion and a few skin sores related to hypothermia. Which of the following biological processes was chiefly responsible for conserving this child's core body temperature during her winter trek? (A) Closing of arteriovenous anastomoses (B) Decreased blood supply to the subcutaneous plexus (C) Increased blood supply to the subpapillary plexus (D) Opening of arteriovenous anastomoses (E) Vasodilation of the microvascular bed in the skin

*The answer is E.* During the period of weight gain, the increased release of norepinephrine from nerve terminals near white adipocytes. Norepinephrine activates hormone-sensitive lipase, whic mobilizes lipids from adipocytes.

A 44-year-old African-American woman visits her family physician for a physical examination at the urging of her husband. She has no current complaints and is taking no medications. She is allergic to erythromycin. She works as a software developer and lives with her 52-year-old husband and 12-year-old daughter. She is a nonsmoker and drinks an occasional glass of wine when she and her husband go out to dinner. She is involved in no regular exercise. Her mother is 66 and suffers from type II diabetes, hyperlipidemia, and hypertension and had a myocardial infarction last year. The patient's father died of a stroke last year at the age of 72. On examination, the patient's blood pressure is 155/100 mm Hg, pulse 84, weight 215 lb (increased from 180 lb 3 years ago), and height 5 ft. 7 in. In this patient, during the period of weight gain which one of the following responses would be most likely in her white fat? a. Increased synthesis of growth hormone b. Decreased synthesis of leptin c. Decreased release of leptin to the blood d. Conversion of beige adipocytes to unilocular white adipocytes e. Increased release of norepinephrine from nerve terminals near white adipocytes

*The answer is E.* Pemphigus vulgaris is a chronic blistering skin disorder, secondary to diminished cohesion between keratinocytes. The blisters are suprabasal, meaning that the stratum basale separates from outer layers of the epidermis (shown in the image). The basal layer is intact and remains adherent to the basement membrane that forms the floor of the blister. The remaining epidermal layers form the roof of the blister. Acute and chronic inflammatory cells may be present within the vesicle. Distinctive, rounded keratinocytes are also shed into the lumen of the vesicle (acantholytic keratinocytes). None of the other layers of the skin exhibit physical separation in patients with pemphigus vulgaris.

A 48-year-old man presents with numerous large blisters on his scalp, around his umbilicus, and in his oral cavity. The patient states that his blisters rupture easily leaving behind large denuded areas. Examination of a skin biopsy suggests the diagnosis of pemphigus vulgaris (shown in the image). The biopsy shows loss of cohesion between which of the following two layers of the patient's skin? (A) Basement membrane and papillary dermis (B) Epidermis and basement membrane (C) Papillary dermis and reticular dermis (D) Reticular dermis and hypodermis (E) Stratum basale and stratum spinosum of epidermis

*The answer is B.* Direct immunofluorescence analysis of the patient's skin reveals a lace-like pattern that outlines individual keratinocytes (shown in the image). This experimental result is consistent with the deposition of immune complexes at points of contact between keratinocytes. The autoantibody formed in patients with pemphigus vulgaris has been shown to recognize desmoglein 3--a major structural protein found in desmosomes (zonula adherens). Desmosomes mediate adhesion between keratinocytes. Desmoglein 3 is more concentrated in the lower portion of the epidermis--a finding that explains loss of cohesion between basal cells and cells in upper layers of the epidermis. None of the other membrane-associated structures serve as primary adhesive junctions between keratinocytes.

A 48-year-old man presents with numerous large blisters on his scalp, around his umbilicus, and in his oral cavity. The patient states that his blisters rupture easily leaving behind large denuded areas. Examination of a skin biopsy suggests the diagnosis of pemphigus vulgaris. Another section of lesional skin from the patient is stained with fluorescein-conjugated goat anti-human IgG antibody. The results of this direct immunolabeling assay demonstrate the presence of autoantibodies bound to junctions between keratinocytes (shown in the image). These autoantibodies bind to which of the following membrane-associated structures? (A) ABO antigens (B) Desmosomes (C) Gap junctions (D) Integrins (E) Tight junctions

*The answer is B.* Actinic keratosis is a form of dysplasia in sun-exposed skin (actin meaning rays). Histologically, such lesions are composed of atypical squamous cells that vary in size and shape. Patches of epidermal dysplasia do not exhibit regular maturation as keratinocytes move from the basal layer of the epidermis to the surface. Dysplasia is a preneoplastic lesion, in the sense that it is a necessary stage in the multistep evolution to cancer. However, unlike cancer cells, dysplastic cells are not entirely autonomous. The histologic appearance of dysplastic tissue may still revert to normal. Adaptive changes in the other cells do not cause epidermal dysplasia.

A 64-year-old farmer presents with multiple patches of discoloration on his face. Biopsy of lesional skin reveals "actinic keratosis." This pathologic condition represents abnormal maturation of which of the following skin cells? (A) Dermal fibroblasts (B) Keratinocytes (C) Langerhans cells (D) Mast cells (E) Melanocytes

*The answer is D.* Melanomas are neoplasms of melanocytes. If not diagnosed and removed at an early stage of tumor progression, melanomas can be deadly. Acral lentiginous melanoma is the most common type of melanoma in the dark-skinned population. This melanoma typically arises in the palm of the hand, sole of the foot, or in a subungual (nail bed) location. During the early radial growth phase, the tumor appears as an irregular, brown-to-black patch. As the disease progresses, neoplastic cells invade the deep dermal layer of the skin (vertical growth phase). These lesions appear as elevated rounded black nodules. Some tumors exhibit ulceration. Basal keratinocytes (choice A) are progenitor cells for basal cell carcinomas. None of the other cells give rise to melanomas.

A 68-year-old man from Africa presents with darkcolored lesions on his left heel. The center of the primary lesion is elevated and ulcerated (the patient's foot is shown in the image). Based on these observations, the patient's skin tumor is derived from which of the following cells? (A) Basal keratinocyte (B) Langerhans cell (C) Macrophage (D) Melanocyte (E) Merkel cell

*The answer is A.* The arrows identify large keratinocytes with numerous cytoplasmic extensions. These cells form the stratum spinosum. This layer is so named, because of the "spinous" appearance of keratinocytes at this stage of maturation. The spinous processes provide focal contact points for adhesion between adjacent cells. Keratinocytes originate from proliferative stem cells in the stratum basale. Newly formed keratinocytes are lifted toward the surface of the skin. As they move, they mature; they develop cytoplasmic extensions (spinous processes), increase in size, and become flattened (shown in the image). The stratum spinosum is several cell layers thick. The other cells do not give rise to keratinocytes.

A section of thick skin from the palm of the hand is examined in the histology laboratory. Multiple cell layers in the epidermis are evident at high magnification. The specimen described is examined at higher magnification (shown in the image). The intraepidermal cells indicated by the large arrows are derived from which of the following precursor cells? (A) Basal cells (B) Langerhans cells (C) Melanocytes (D) Merkel cells (E) Monocytes

*The answer is D.* Sebaceous glands are branched acinar glands embedded in the dermis. A short duct delivers the secretory products of several acini to the upper portion of the hair follicle. Sebaceous glands develop as an outgrowth of the external root sheath of the hair follicle (shown in the image). Undifferentiated, flattened epithelial cells surround the periphery of glandular acini. The epithelial cells constantly proliferate, move toward the center of the acinus, and differentiate into large lipid-producing cells with fat droplets in their cytoplasm. Sebum, the oily product of the sebaceous gland, is released following rupture of the cells. This process is referred to as holocrine secretion. Sebum moves to the skin surface by following the path of the hair follicle. Sebum has antimicrobial and proinflammatory activities and serves to protect the stratum corneum of the epidermis.

A skin biopsy is obtained from a 34-year-old man. Formalin-fixed tissue is stained with H&E and examined by light microscopy (shown in the image). Identify the structure indicated by the arrow. (A) Blood vessel (B) External root sheath (C) Hair follicle (D) Sebaceous gland (E) Sweat gland

*The answer is D.* Leptin is a 16-kD polypeptide hormone produced by adipocytes in white adipose tissue. It acts on leptin receptors in the hypothalamus to regulate food intake and energy use. Unlike short-term weight control hormones, such as peptide YY, inhibition of appetite by leptin has a long-term effect on weight. Absence or decreased serum levels of leptin result in uncontrolled food intake and obesity. Cholecystokinin (choice A) is secreted by mucosal epithelial cells of the small intestine and regulates digestion in the small intestine by stimulating the release of digestive enzymes and bile. Glucagon (choice C) is secreted by the pancreas and raises blood glucose levels. Together with insulin, glucagon helps maintain stable levels of blood glucose. Melatonin (choice E), secreted by the pineal gland, regulates the rhythmic sleep-wake cycle. Ghrelin (choice B) is produced by the small intestine and functions as a "meal initiator" by stimulating the sense of hunger. Overproduction of ghrelin in patients with Prader-Willi syndrome can cause compulsive eating and obesity.

An obese, 18-year-old man (BMI = 32 kg/m2) presents with questions regarding his weight. The patient admits to an unusually strong appetite and uncontrolled food intake. His behavior may be related to decreased serum concentration of which of the following hormones? (A) Cholecystokinin (B) Ghrelin (C) Glucagon (D) Leptin (E) Melatonin

*The answer is E.* The hair matrix (zone of dividing and differentiating cells) of the hair bulb are responsible for producing the pigment for dark hair.

Cells responsible for producing the pigment for dark hair are located in which of following? a. The cortex of the hair shaft b. Throughout the hair shaft c. The internal root sheath of the hair d. The dermal papilla of the hair bulb e. The hair matrix (zone of dividing and differentiating cells) of the hair bulb

*The answer is C.* Eccrine sweat glands produce as much as 10 L of sweat per day. The initial sweat produced by the secretory portions of the glands is similar in composition to an ultrafiltrate of the blood. Reabsorption of sodium and water occurs in the excretory ducts. This results in a hypotonic sweat that is released to the skin surface. Evaporation of sweat from the body surface serves to cool the skin. Sweating is a physical response to (1) elevated body temperature during exercise or fever and (2) high ambient temperature. Eccrine sweat glands are innervated by sympathetic nerve fibers and are stimulated by cholinergic neurotransmitters. In response to thermal stress, eccrine sweat glands are the most effective temperature regulator in the body. Emotional stress (e.g., fear) is associated with the release of adrenergic neurotransmitters that stimulate sweating from the palms and soles. None of the other epidermal appendages are involved in thermoregulation.

During a 3rd year clinical rotation, you are asked to discuss the biological functions of the skin. Thermoregulation is the primary function of which of the following epidermal appendages? (A) Apocrine sweat glands (B) Arrector pili muscles (C) Eccrine sweat glands (D) Hair follicles (E) Sebaceous glands

*The answer is D.* The stratum lucidum is composed of eosinophilic and refractile cells that are only visible in thick skin. These cells are located between the stratum granulosum and the stratum corneum. They represent an intermediate stage in the transformation of nucleated granular cells to form flattened, desiccated anucleate cells. When keratinocytes .in the stratum spinosum release filaggrin and trichohyalin, their keratin filaments aggregate to form bundles that are referred to as tonofibrils. Thus, filaggrin and trichohyalin initiate the transformation of granular cells to cornified cells. This process is termed keratinization. During keratinization, cell nuclei and cytoplasmic organelles are degraded, and plasma membranes are thickened. The cells in the stratum lucidum layer appear pink, because the tonofibrils are eosinophilic when stained with H&E.

During a dermatopathology conference, you are asked about differences between thick and thin skin. Which of the following epidermal layers is a unique feature of thick skin? (A) Stratum basale (B) Stratum corneum (C) Stratum granulosum (D) Stratum lucidum (E) Stratum spinosum

*The answer is B.* When exposed to sunlight (ultraviolet light), the skin can rapidly produce vitamin D3 (cholecalciferol) from the precursor molecule, 7-dehydrocholesterol. Synthesis of vitamin D3 occurs primarily in the stratum basale and stratum spinosum of the epidermis. The skin is the major source of vitamin D3, particularly in areas where dietary sources of vitamin D3 are lacking. Vitamin D3 enhances the intestinal absorption of calcium and phosphate, which are essential for the development of healthy bones and teeth. Deficiency of vitamin D3 leads to osteomalacia in adults and rickets in children. None of the other skin cells synthesize vitamin D3 when exposed to sunlight.

During small group seminar, you are asked to discuss the metabolism and function of vitamin D. You mention that the skin synthesizes vitamin D3 when exposed to sunlight. Which of the following cells in the skin is responsible for the production of vitamin D3? (A) Fibroblasts in the dermis (B) Keratinocytes in strata basale and spinosum (C) Keratinocytes in the stratum granulosum (D) Melanocytes in the epidermis (E) Merkel cells in the epidermis

*The answer is D.* Sweat glands contain myoepithelial cells in their secretory portion.

In skin A. the epidermis has no nerve endings B. pluripotential cells in the stratum germinativum differentiate into melanocytes, Langerhans cells and keratinocytes C. the papillary layer of the dermis abuts on the hypodermis D. Sweat glands contain myoepithelial cells in their secretory portion

*The answer is A.* Down growth of epidermal epithelial cells (particularly the basal and spinous layers) into the dermis is referred to as the external root sheath. The invaginating epidermis is accompanied by its basement membrane deep into the dermis. Here, the basement membrane becomes thickened and is referred to as the "glassy membrane." Dense, irregular connective tissue surrounding the follicle forms a connective tissue sheath. The glassy membrane separates the hair follicle from the surrounding connective tissue sheath. None of the other cutaneous structures are continuous with the glassy membrane of the hair follicle.

In the image shown, the red-stained, acellular hyaline layer indicated by the arrowhead is continuous with which of the following cutaneous structures? (A) Basement membrane (B) Collagen bundles in reticular dermis (C) Collagen fibers in papillary dermis (D) Hypodermis (E) Stratum corneum

*The answer is D.* The skin biopsy shows a postcapillary venule that is nearly obliterated by a neutrophilic infiltrate. These histopathologic findings suggest a diagnosis of cutaneous necrotizing vasculitis. Damage to the vessel wall is associated with fibrin deposition and extravasation of erythrocytes (shown in the image). The lesions usually develop in the postcapillary venules that drain from capillary loops to the subpapillary venous plexus. Postcapillary venules are known to regulate the movement of inflammatory cells from the vascular space to regions of tissue injury during inflammation. Cutaneous necrotizing vasculitis may be primary (without a known cause) or secondary (e.g., caused by deposition of immune complexes). None of the other blood vessels are principal targets for immune complex-mediated inflammation in patients with cutaneous necrotizing vasculitis.

A 25-year-old woman with a recent history of "strep throat" presents with numerous tender, red papules on her legs. Histological examination of a skin biopsy reveals pink fibrin deposits and remnants of neutrophils surrounding small blood vessels (shown in the image). The patient is subsequently diagnosed with cutaneous necrotizing vasculitis. This inflammatory/immune reaction typically affects which of the following blood vessels? (A) Arteries in the subcutaneous plexus (B) Arterioles in the deep reticular dermis (C) Arteriovenous anastomoses in the hypodermis (D) Postcapillary venules in the subpapillary plexus (E) Veins in the subcutaneous plexus

*The answer is B.* Melanin absorbs ultraviolet radiation and protects the skin from the harmful effects of sunlight. Harmful effects of sunlight exposure on the skin include inhibition of metabolism, generation of reactive oxygen species, activation of programmed cell death, mutagenesis, and cancer. Cancers linked to ultraviolet radiation including basal cell carcinoma, squamous cell carcinoma, and melanoma. Tanning, therefore, is a highly beneficial, reversible cellular adaptation. As a response to ultraviolet radiation exposure, melanocytes increase in cell number (hyperplasia) and accelerate their production of melanin. Increased pigmentation protects the skin against the harmful effects of sunlight. None of the other biological processes are related to the development of a suntan.

A 28-year-old white woman returns home following a 4-week summer vacation at the beach. Her friends and family comment that her skin has become much darker in color. Which of the following biological processes accounts for this change in skin coloration? (A) Increased number of granular keratinocytes (B) Increased production of melanin (C) Increased thickness of the stratum corneum (D) Migration of melanocytes into the stratum corneum (E) Slower degradation of melanin

*The answer is B.* Epidermolysis bullosa (EB) refers to a heterogeneous group of inherited connective tissue disorders that cause blisters in the skin and mucosal membranes. Over 300 mutations in genes encoding extracellular macromolecules have been detected in patients with EB. Junctional EB is associated with mutations in the gene for type XVII collagen, as well as genes for laminins and integrins. Type XVII collagen is a transmembrane protein and a component of hemidesmosomes at the epidermal-basement membrane junction. It anchors keratinocytes to the underlying basement membrane. Mutations in the collagen XVII gene lead to diminished epidermal adhesion and blistering following minimal shearing forces. Loss of cohesion between the basement membrane and papillary dermis (choice A) is associated with dermolytic EB, a blistering skin disease caused by mutations in the gene for type VII collagen. Disintegration within the basal layer of epidermal cells is seen in patients with epidermolytic EB. None of the other choices are related to the pathogenesis of EB.

A 3-day-old neonate suffers extensive blisters in his oral mucosa and skin. Laboratory studies reveal a mutation in the gene encoding type XVII collagen, and the patient is diagnosed with junctional epidermolysis bullosa. A skin biopsy taken from the back of the neonate reveals normal tissue at the margin of a blister (shown in the image). The congenital blistering disease described caused by loss of cohesion between which of the following layers of the patient's skin? (A) Basement membrane and papillary dermis (B) Epidermis and basement membrane (C) Papillary dermis and reticular dermis (D) Reticular dermis and hypodermis (E) Stratum spinosum and stratum basale of epidermis

*The answer is C.* The skin consists of two firmly adherent tissue layers, namely epidermis and dermis. Epidermis, the most superficial layer, is composed of a keratinized, stratified squamous epithelium. The basal cell layer of this stratified epithelium is firmly anchored to an underlying basement membrane. Dermis (choice B) represents connective tissue beneath the epidermis. This layer is subdivided into papillary and reticular dermis. Epidermis is derived from embryonic ectoderm, whereas dermis is derived from embryonic mesoderm. Hypodermis (choice D) represents the layer of adipose connective tissue located deep to the skin. This subcutaneous tissue represents the layer of superficial fascia that is identified in gross anatomy.

A 3-day-old neonate suffers extensive blisters in his oral mucosa and skin. Laboratory studies reveal a mutation in the gene encoding type XVII collagen, and the patient is diagnosed with junctional epidermolysis bullosa. A skin biopsy taken from the back of the neonate reveals normal tissue at the margin of a blister (shown in the image). Identify the layer indicated by the arrow. (A) Dermal papilla (B) Dermis (C) Epidermis (D) Hypodermis (E) Reticular dermis

*The answer is C.* The dermis is composed of a superficial papillary layer and a deep reticular layer. The papillary layer, located immediately beneath the epidermis, is composed of loose connective tissue. Type I and type III collagen fibers and thread-like elastic fibers form an irregular network. This layer is more cellular than the reticular dermis. It contains numerous blood vessels, lymphatic vessels, and sensory nerve endings. The papillary dermis also forms finger-like protrusions into the overlying epidermis (referred to as dermal papillae). The deeper reticular layer of the dermis (choice D) is composed of dense, irregular connective tissue. It is less cellular than papillary dermis and contains an abundance of thick type I collagen fiber bundles and coarse elastic fibers (see Chapter 3). Hypodermis and subcutis (choices B and E) describe adipose connective tissue that is located deep to the reticular dermis.

A 3-day-old neonate suffers extensive blisters in his oral mucosa and skin. Laboratory studies reveal a mutation in the gene encoding type XVII collagen, and the patient is diagnosed with junctional epidermolysis bullosa. A skin biopsy taken from the back of the neonate reveals normal tissue at the margin of a blister (shown in the image). The skin biopsy is examined at higher magnification (shown in the image). The area indicated by the asterisk is best described as which of the following? (A) Epidermis (B) Hypodermis (C) Papillary dermis (D) Reticular dermis (E) Subcutis

*The answer is C.* Epithelial cells surrounding the dermal papilla are collectively referred as the hair matrix. Matrix cells represent the proliferative (germinative) layer of the hair follicle, comparable to cells of the stratum basale of the epidermis. Matrix cells differentiate into keratin-producing cells of the hair. Continuous proliferation and division of these cells account for the growth of hair. Melanocytes are scattered among the matrix cells and pass melanin to the developing hair cells, thereby providing the hair with its natural color. Matrix cells also differentiate to form cells making up the internal root sheath (choice D). The internal root sheath consists of multiple cell layers and completely covers the initial part of the hair shaft. It degenerates near the level of the associated sebaceous glands. Dermal papilla (choice A) is composed of connective tissue whose primary function is to provide the vascular supply to the growing hair follicle. Inductive interactions between dermal papillae and matrix cells within the hair bulb are believed to regulate the size and shape of hair. The external root sheath (choice B) contains stem cells resembling epidermal basal cells (choice E); however, these cells do not contribute directly to the growth of hair.

A 32-year-old Asian man notices that he is losing hair and is concerned about becoming bald. You talk to him about the mechanisms that regulate hair growth. Cells in which of the following regions of the hair follicle are directly responsible for the growth of hair? (A) Dermal papilla (B) External root sheath (C) Hair matrix (D) Internal root sheath (E) Stratum basale in epidermis

*The answer is E.* The arrow indicates a sebaceous gland in the section of scalp shown in the micrograph. Sebum is released when cells in the gland rupture and release their contents into hair follicles, a mechanism termed holocrine secretion.

A 35-year-old man visits the clinic because he has a cyst on his scalp that has a foul-smelling drainage. The man reports that the drainage occurs spontaneously, and recently the cyst has enlarged and become painful. The cyst is associated with the structure in the micrograph indicated by the arrow. Which mechanism of secretion is normally used by this structure? A. Apocrine B. Autocrine C. Cytocrine D. Eccrine E. Holocrine F. Merocrine

*The answer is A.* Lamellated (pacinian) corpuscles are used to sense coarsh touch, pressure, and vibrations.

A 37-year-old woman presents with a suspected Schwannoma. The radiology report indicates "a soft tissue mass to the right of L1 at the level of the L1 to L2 neural foramen." The neurologist presses the base of a vibrating 128 cps tuning fork to the skin of the patient's right and left thighs and asks her to describe the sensation. She asks the patient to close her eyes and then to tell her whether the tuning fork is vibrating or not. With that instrument the doctor is primarily testing the function of which of the following sensory receptors? a. Lamellated (Pacinian) corpuscles b. Kraus end bulbs c. Meissner corpuscles d. Merkel cells e. Free nerve endings

*The answer is C.* Scleroderma is a chronic autoimmune disease characterized by excessive collagen deposition in the skin and internal organs. Initial cutaneous lesions of scleroderma affect the lower reticular dermis. The entire dermis is eventually affected. Large, tightly packed collagen bundles parallel to the skin surface are a characteristic histologic finding in patients with scleroderma. Sweat glands and hair follicles are eventually destroyed, owing to the lack of adequate arterial blood supply. The affected skin becomes hard, stiff, and tense. The skin over the face becomes masklike and patients appear expressionless. The hypodermis (choice B) is usually not involved in early stages of this disease. The other regions/structures are typically spared in patients with scleroderma.

A 38-year-old woman complains stiff and tense skin over her face and hands. Physical examination reveals radial furrows around the patient's mouth. The patient does not display facial expression during her visit. A skin biopsy is obtained (shown in the image). The patient is subsequently diagnosed with scleroderma. The histopathologic findings in this biopsy are consistent with excess collagen deposition in which of the following cutaneous locations? (A) Basement membrane (B) Hypodermis (C) Reticular dermis (D) Stratum basale (E) Stratum corneum

*The answer is C.* Brown adipose tissue responds to cold by releasing energy as heat, rather than using it to make ATP.

Ten days after birth a full-term newborn boy develops firm, erythematous nodules and plaques over his trunk, arms, buttocks, thighs, and cheeks. His mother's pregnancy was complicated by placenta previa and his airway was cleared of aspirated meconium immediately after birth. A biopsy of subcutaneous tissue shows necrosis within the brown adipose tissue. What metabolic activity is liable to be affected in this patient? a. Export of fatty acids from fat b. Thermal insulation c. Oxidation of fatty acids for thermogenesis d. Activation of the adenylate cyclase system e. Initiation of shivering

*The answer is E.* Pacinian corpuscles are encapsulated tactile mechanoreceptors embedded in the deep dermis and hypodermis. They are large oval "onion-like" structures, with an outer capsule and numerous thin, concentric lamellae. A highly branched unmyelinated axon ending is present in the center of the corpuscle. The cellular concentric lamellae consist primarily of flattened Schwann cells. Collagen fibers and capillaries may be seen in the spaces between lamellae. Pacinian corpuscles are specialized for sensation of deep pressure and transient vibrations via displacement of capsular lamellae. Free nerve endings (choice A) are axon terminals that lack a Schwann cell or connective tissue covering. Free nerve endings are found in the epidermis and cornea of the eye. Nerve fibers (choice D) are seen throughout the dermis as a collection of myelinated nerve axons. None of the other choices describe the distinctive features of a pacinian corpuscle.

The deep dermis of a skin biopsy from the tip of a finger is examined in the pathology department (shown in the image). Identify the structure indicated by the arrow. (A) Free nerve ending (B) Meissner corpuscle (C) Merkel disk (D) Nerve fiber (E) Pacinian corpuscle

*The answer is C.* The stratum granulosoum of the epidermis contain lipid containing sheets that are impermeable to water. The lamellar granules undergo exocytosis, producing a lipid-rich, impermeable layer around the cells. This material forms a major part of the skin's barrier against water loss.

The intercellular spaces in the stratum granulosoum of the epidermis contain lipid containing sheets that are impermeable to water. This material is released from which of the following? A. Keratohyalin granules B. Langerhans cells C. Lamellar bodies D. Sebaceous glands E. Melanosomes

*The answer is B.* Meissner corpuscles are encapsulated receptors specialized for the detection of shape and texture during active touch. They are found primarily in the fingertips and toes. These elliptical structures are situated within the cores of dermal papillae, with their long axis perpendicular to the surface of the skin. The "twisted skein of wool" appearance is due to a spiral arrangement of Schwann cells. Several unmyelinated endings of myelinated axons course through the Schwann cell corpuscle. Capillary loops (choice A) are found in dermal papillae; however, these tubular structures usually exhibit a lumen. None of the other structures exhibit the distinctive features of a Meissner corpuscle.

The papillary dermis from a skin biopsy is examined at higher magnification (shown in the image). Identify the structure indicated by the arrow. (A) Capillary loop (B) Meissner corpuscle (C) Merkel disk (D) Myelinated nerve fiber (E) Pacinian corpuscle

*The answer is A.* The skin is richly supplied with blood through two major vascular plexuses: deep and superficial. Cutaneous arteries and veins traveling in the hypodermis form a deep subcutaneous (hypodermic) plexus. Ascending arterioles arising from arteries in the hypodermis cross the reticular dermis. Near the border of the papillary dermis, neighboring ascending arterioles anastomose to form a superficial or subpapillary plexus. Terminal arterioles extend from the subpapillary plexus into each dermal papilla, forming a single capillary loop that supplies the epidermis via passive diffusion. Postcapillary venules return to the venous plexus in the subpapillary plexus. Small arteries and veins (choices D and E) are not present in dermal papillae. None of the other structures are characterized by the presence of a lumen.

The papillary dermis of a skin biopsy described is examined further (shown in the image). Identify the structures indicated by the arrows. (A) Capillary loops (B) Free nerve ending (C) Meissner corpuscles (D) Small arteries (E) Small veins

*The answer is D.* In white adipose tissue, adipocytes are large, crowded, polyhedral cells. The cells are filled with one single droplet of lipid (i.e., unilobular cells). The cytoplasm and nucleus are pushed to the periphery of the cell. In routine histological preparations, lipid extraction during tissue processing causes adipocytes to assume a signet ring profile. Excessive energy intake with less energy expenditure results in obesity, with a significant accumulation of adipose tissue. In childhood, obesity results from increases in the size (hypertrophy) of adipocytes, as well as the formation of new adipocytes (hyperplasia). In adults, obesity principally involves accumulation of lipid within existing adipocytes (hypertrophy). Multilocular adipose tissue (choices A and B), termed brown adipose tissue, is mainly found in newborns. Unilocular adipose tissue with cellular hyperplasia (choice C) occurs in early childhood but does not contribute to the pathogenesis of adult obesity.

Thick Camper fascia from the abdomen of a 72-year-old man is examined at autopsy (shown in the image). Which of the following best describes histologic features of this tissue? (A) Multilocular adipose tissue with cellular hyperplasia (B) Multilocular adipose tissue with cellular hypertrophy (C) Unilocular adipose tissue with cellular hyperplasia (D) Unilocular adipose tissue with cellular hypertrophy (E) Unilocular adipose tissue with cellular metaplasia

*The answer is C.* High frequency repetitive stimulation (indentation/pressure) of the skin is sensed by Pacinian corpuscles.

Vibratory sensation is dependent on the detection of rapidly changing, repetitive sensations. The high-frequency end of the repetitive stimulation scale is detected by which of the following? A) Merkel's discs B) Meissner's corpuscles C) Pacinian corpuscles D) Free nerve endings

*The answer is C.* The arrow on the micrograph indicates a Meissner's corpuscle in a dermal papilla in thick skin on the fingertip. Meissner's corpuscles respond to light touch, and are responsible for tactile discrimination.

What is the function of the structure and indicated by the arrow on the micrograph? A. Detection of cold and heat (thermoreception) B. Detection of deep pressure C. Detection of light touch D. Detection of pain (nociception) E. Detection of vibration

*The answer is C.* Norepinephrine released from the adrenal gland and some autonomic neurons increases lipolytic activity in white adipocytes.

What substance, released from the adrenal gland and some autonomic neurons, increases lipolytic activity in white adipocytes? a. Leptin b. Insulin c. Norepinephrine d. Glycogen e. Triglyceride

*The answer is B.* Langerhans cells are specialized dendritic cell, found in the skin and mucosa, that is involved in the immune response and acts as a macrophage.

Which cells derive from precursors originating in the bone marrow and function as antigen-presenting cells in skin? a. Keratinocytes b. Langerhans cells c. Melanocytes d. Merkel cell e. Arrector pili

*The answer is E.* The epidermis is subjected to a great deal of wear and tear, and undergoes constant cellular turnover to replace dead or damaged cells. Layer E designates the stratum basale (germinativum), a single basal layer composed primarily of mitotically active keratinocytes. Scattered stem cells in the stratum basale and lower stratum spinosum (layer D) produce all of the keratinocytes in the epidermis.

Which letter on the micrograph indicates the layer in which mitosis is most commonly observed?

*The answer is B.* Sebaceous glands are oil glands in the skin, which produce oily sebum to lubricate and waterproof hair. It releases sebum via holocrine secretion.

Which of the following best characterizes sebaceous glands? a. Its duct drains onto the skin surface. b. It releases its contents via holocrine secretion. c. It primarily secretes water and salts. d. Its secretory units are supplied by adrenergic stimulation. e. It is located typically in the reticular dermis

*The answer is E.* The nail is one appendage of the skin. Other skin appendages are hair follicles, sweat glands, and sebaceous glands.

Which of the following is an appendage of skin? (A) Meissner corpuscle (B) Langerhans cell (C) Krause end-bulb (D) Pacinian corpuscle (E) Nail

*The answer is C.* Meissner's corpuscles are found in the dermal pegs.

Which of the following is best described as an elongated, encapsulated receptor found in the dermal pegs of glabrous skin and is especially abundant on lips and fingertips? A) Merkel's disc B) Free nerve endings C) Meissner's corpuscle D) Ruffini's endings

*The answer is D.* Langerhans cells in the epidermis function as antigen-presenting cells by trapping antigens that penetrate the epidermis and transporting them to regional lymph nodes, where they are presented to T lymphocytes. In this way, these cells assist in the immune defense of the body. They originate in the bone marrow and do not arise from epithelium.

Which of the following statements about Langerhans cells is true? (A) They commonly are found in the dermis. (B) They function as sensory mechanoreceptors. (C) They function as receptors for cold. (D) They play an immunological role in the skin. (E) They are of epithelial origin.

*The answer is A.* Melanocytes are present in the stratum basale of the epidermis. They synthesize melanin pigment and transfer it to keratinocytes to protect against damage caused by UV radiation. Melanocytes sometimes give rise to a form of skin cancer called malignant melanoma. They derive from neural crest and migrate into the epidermis early during embryonic development.

Which of the following statements concerning skin melanocytes is true? (A) They synthesize a pigment that protects against damage caused by UV radiation. (B) They are located only in the dermis. (C) They produce keratohyalin granules. (D) They may give rise to basal cell carcinoma. (E) They originate from the mesoderm.

*The answer is D.* The stratum granulosum contains a number of dense keratohyalin granules but not melanosomes. It lies just deep to the stratum lucidum and is a relatively thin layer in the epidermis of thick skin. Only rarely would a cell undergo mitosis in this layer of the skin.

Which of the following statements concerning the stratum granulosum is true? (A) It contains melanosomes. (B) It lies superficial to the stratum lucidum. (C) It is the thickest layer of the epidermis in thick skin. (D) It contains keratohyalin granules. (E) It contains large numbers of dividing cells.

*The answer is D.* In contrast to thick skin, which lacks hair follicles, thin skin contains many of them.

Which of the following statements concerning thin skin is true? (A) It does not contain sweat glands. (B) It lacks a stratum corneum. (C) It is less abundant than thick skin. (D) It contains hair follicles. (E) Its epidermis does not rest on a basement membrane.

*The answer is B.* The reticular layer is a thick deep layer of the dermis, which consists of dense irregular connective tissue and a network of elastic fibers. This supplies the skin with oxygen and nutrients.

Which structure typifies reticular dermis but not papillary dermis? a. Capillaries b. Dense irregular connective tissue c. Meissner tactile corpuscles d. Sweat gland ducts e. Type I collagen fibers

*The answer is C.* Adipocytes are derived developmentally from mesenchymal cells.

White adipocytes are derived developmentally from what precursor cells? a. Monocytes b. Fibroblasts c. Mesenchymal cells d. Brown adipocytes e. Mast cells

*The answer is B.* Apocrine sweat glands are tubular glands with large lumens. Like eccrine sweat glands, the secretory portions of apocrine sweat glands are embedded in the dermis and hypodermis. However, unlike eccrine sweat glands, their ducts open into hair follicles. Apocrine sweat glands are limited in distribution to axillary and perineal regions of the body and do not develop fully until puberty. The feature that distinguishes apocrine from eccrine sweat glands is the large size of their lumens. The secretory cells in apocrine sweat glands are simple cuboidal and eosinophilic. Myoepithelial cells are located between secretory cells and the basal lamina. The secretions of apocrine sweat glands contain proteins, carbohydrates, lipids, ammonia, and other organic compounds. These odorless secretions develop an acrid odor, through the action of microbes at the skin surface. The excretory ducts of apocrine sweat glands (choice A) are similar to those of eccrine sweat glands, but they take a more direct course and empty into hair follicle canals. The secretory portions of eccrine sweat glands (choice D) exhibit a pseudostratified epithelium and have a much smaller lumen. None of the other structures describe the histological features of apocrine sweat glands.

A sample of skin from the axillary region is collected at autopsy and examined in the pathology department (shown in image). Identify the structures indicated by the arrows. (A) Apocrine sweat gland, excretory portion (B) Apocrine sweat gland, secretory portion (C) Eccrine sweat gland, excretory portion (D) Eccrine sweat gland, secretory portion (E) Subcutaneous vascular plexus

*The answer is D.* Hair is present over most of the body surface, except for the skin of the palms, soles, lips, glans penis, clitoris, and labia minora. Hairs are filamentous keratinized structures derived from follicles. Hair follicles are invaginations of the epidermis that extend from the surface of the epidermis to the deep reticular dermis and/or hypodermis. Follicles are responsible for the continuous growth of hair. In this low-magnification image, transverse sections of several hair follicles exhibit epidermal epithelial cell sheaths surrounding centrally located hair shafts. Sebaceous glands (choice E) are associated with hair follicles (arrowheads, shown in the image). Eccrine sweat glands (choice C) are indicated by the oval in the image. Apocrine sweat glands (choice A) are not present in the scalp.

A scalp biopsy is examined in the pathology department (shown in the image). Identify the structures indicated by the arrows. (A) Apocrine sweat glands (B) Arteries (C) Eccrine sweat glands (D) Hair follicles (E) Sebaceous glands

*The answer is E.* Eccrine sweat glands are widely distributed over the body surface, but they are lacking in the skin of the lips and parts of the external genitalia. Eccrine sweat glands are epidermal appendages that are independent of hair follicles. They are embedded in the dermis and hypodermis, and their excretory ducts open to the skin surface. Eccrine sweat glands are simple, coiled tubular structures consisting of two segments (or portions), namely secretory and excretory. When stained with H&E, the secretory portions appear more pale stained than do excretory portions. They are composed of a pseudostratified epithelium with a small lumen. By contrast, excretory ducts (choice B) are lined by a distinctive, stratified cuboidal epithelium (arrowheads, shown in the image). Ductal epithelial cells are smaller and darker than secretory cells. Apocrine sweat glands (choice A) feature large secretory acini. They are present in the axilla, mons pubis, and perianal area. Hair follicles and sebaceous glands (choices C and D) do not exhibit the histological features of eccrine sweat glands.

A section of palm skin is examined in the histology laboratory. Distinctive clusters of cells are seen embedded in the dermis and hypodermis (shown in the image). Identify the structures indicated by the arrows. (A) Apocrine sweat glands (B) Ducts of eccrine sweat glands (C) Hair follicles (D) Sebaceous glands (E) Secretory portion of eccrine sweat glands

*The answer is A.* Skin is classified as thick or thin based on the relative thickness of the epidermis. Thick skin on the palm of the hand and sole of the foot lacks hair and has a much thicker epidermal layer than does thin skin covering other regions of the body. Keratinocytes composing the epidermis are arranged into five layers (strata) in thick skin and four layers in thin skin. Stratum basale, the deepest layer, consists of a single layer of cuboidal/low columnar epithelial cells. This basal layer contains proliferative stem cells that give rise to new keratinocytes. For this reason, the stratum basale is also referred to as the stratum germinativum. Basal cells in this photomicrograph appear small, and their nuclei are closely spaced and aligned in a row. Melanocytes are interspersed within the stratum basale. These neural crest-derived cells synthesize a melanin pigment that is transferred into the cytoplasm of neighboring basal cells—many of which appear dark brown in this image. Basal cells are connected to one another and to the upper layer of keratinocytes through desmosomes. They are connected to the underlying basement membrane through hemidesmosomes.

A section of thick skin from the palm of the hand is examined in the histology laboratory. Multiple cell layers in the epidermis are evident at high magnification (shown in the image). Identify the layer indicated by the arrows (A) Stratum basale (B) Stratum corneum (C) Stratum granulosum (D) Stratum lucidum (E) Stratum spinosum

*The answer is B.* As keratinocytes move up through the stratum spinosum, they accumulate intracellular "keratohyalin" granules. These most superficial cells of the nonkeratinized portion of the epidermis constitute the stratum granulosum. This layer is about one-to-three cells thick. Keratohyalin granules become more abundant as keratinocytes approach the surface of the skin. The granules contain two major intermediate filament-associated proteins, namely filaggrin and trichohyalin. These proteins are released into the cytoplasm, where they promote the aggregation of keratin filaments (choice D) in cornified cells of the stratum corneum. These proteins are intensely basophilic, and they acquire a dark blue color when stained with H&E. Melanin (choice E) is synthesized by melanocytes. None of the other biomolecules are stored in keratohyalin granules.

A section of thick skin from the palm of the hand is examined in the histology laboratory. Multiple cell layers in the epidermis are evident at high magnification. Further examination of the specimen reveals a population of epidermal cells containing dark, cytoplasmic granules (arrowheads, shown in the image). These large granules are filled with which of the following essential biomolecules? (A) Cathepsin (B) Filaggrin (C) Hyaluronan (D) Keratin (E) Melanin

*The answer is D.* The secretory epithelium of eccrine sweat glands consists of three cell types: (1) clear cells, (2) dark cells, and (3) myoepithelial cells. Myoepithelial cells are stellate cells with long processes. These cells are limited to the basal aspect of the secretory portion of the gland. They are located between the secretory cells. Myoepithelial cells are contractile cells that help propel sweat into the excretory duct for transport to the surface of the skin. Numerous contractile filaments in the cytoplasm of myoepithelial cells stain deeply with eosin, making these cells readily identifiable in H&E preparations. In the cross section of a secretory portion shown in the image, small cross sections of myoepithelial cytoplasm are evidently stained with eosin (indicated by the arrowheads). Clear cells (choice A) rest on the basal lamina. They store abundant glycogen in their cytoplasm and, therefore, appear pale stained in routine H&E preparations. Clear cells secrete most of the water and electrolytes in sweat. Dark cells (choice B) are located on top of the clear cells and line the luminal surface. Dark cells secrete glycoproteins. Fibroblasts (choice C) can be seen in the surrounding connective tissue (shown in the image). In longitudinal sections, myoepithelial cells may exhibit features of smooth muscle cells.

The secretory portion of the eccrine sweat gland is examined at higher magnification (shown in the image). Identify the cells indicated by the arrows. (A) Clear cells (B) Dark cells (C) Fibroblasts (D) Myoepithelial cells (E) Smooth muscle cells

*The answer is D.* The skin is the largest organ in the body and, as such, provides an extensive surface area for the processing external stimuli. A rich supply of terminal nerve fibers and a variety of sensory receptors are found in the dermis and epidermis. Some myelinated afferent (sensory) nerve fibers lose their myelin sheath when penetrating the epidermal basement membrane. These nerve endings expand into a disc or plate that is closely associated with the base of a Merkel cell, forming a Merkel disk or tactile disc. The Merkel disk serves as tactile mechanoreceptor. Merkel cells are derived from the neural crest. They are situated among basal keratinocytes in the stratum basale. Uncontrolled malignant proliferation of Merkel cells is referred to as a Merkel cell carcinoma. None of the other cells serve as neural receptors in the skin.

The skin is richly innervated by sensory nerve fibers and contains a variety of sensory receptors. Which of the following epidermal cells is closely associated with terminal nerve fibers and serves as a mechanoreceptor in the skin? (A) Basal cell (B) Langerhans cell (C) Melanocyte (D) Merkel cell (E) Spinous keratinocyte

*The answer is B.* With the formation of tonofibrils, granular cells are converted into cornified (keratinized) cells that leave the stratum granulosum and enter the stratum corneum. The stratum corneum is composed of mature squamous epithelial cells. The cytoplasm of these anucleated cells is filled with keratin filaments. Superficial cells are continuously sloughed off from the surface of the skin (exfoliation). The stratum corneum is constantly renewed by keratinocytes arising from deeper layers of the epidermis. The thickness of the stratum corneum varies depending on anatomic location. It is the thickest in the palm of the hand and the sole of the foot, where the skin is subject to constant abrasion ("wear and tear"). None of the other strata constitute the superficial layer of the epidermis.

The skin of the palm is examined at low magnification in the pathology department (shown in image). Identify the epidermal layer indicated by the arrow. (A) Stratum basale (B) Stratum corneum (C) Stratum granulosum (D) Stratum lucidum (E) Stratum spinosum