Chapter 3

Connective Tissue

QUESTIONS 3 A 43-year-old woman presents with a mass in her right

Select the single best answer.
breast that she first detected 4 months ago. A firm 4-cm
mass is palpated on breast examination. An excisional
1 A 60-year-old woman presents with several small, pearly biopsy is obtained (shown in the image). The area indi-
nodules on the back of her neck. A biopsy of one lesion cated by arrows is primarily composed of which of the
reveals a basal cell carcinoma and adjacent areas of nor- following types of connective tissue?
mal skin (shown in the image). The area indicated by the
asterisk is typically composed of which of the following
tissue types?

(A) Dense irregular

(B) Dense regular
(C) Elastic
(A) Dense, irregular connective tissue (D) Loose
(B) Dense, regular connective tissue (E) Reticular
(C) Glandular epithelium
(D) Skeletal muscle 4 Which of the following cells are responsible for the syn-
(E) Smooth muscle thesis and deposition of collagens and other extracellular
matrix proteins in the area of the breast biopsy specified
2 For the biopsy described in Question 1, which of the in Question 3?
following types of connective tissue is found directly (A) Adipocytes
beneath the basophilic surface epithelium? This tissue is (B) Fibroblasts
highly cellular and contains capillary loops that provide (C) Glandular epithelial cells
nutrients and oxygen to the overlying epithelium. (D) Macrophages
(A) Adipose tissue (E) Plasma cells
(B) Dense irregular connective tissue
(C) Elastic connective tissue 5 A biopsy of an axillary lymph node from the patient
(D) Loose connective tissue described in Question 3 is examined by light micros-
(E) Reticular connective tissue copy. In this silver-stained section (shown in the
image), the irregular black lines indicated by the arrows
30
 Connective Tissue 31
represent which of the following stromal connective 9 A 68-year-old man presents with a 2-week history of
tissue components? abdominal discomfort. A CT scan reveals a dilated and
calcified segment of the abdominal aorta proximal to the
bifurcation. Prior to surgery, the patient suffers a massive
heart attack and expires. The abdominal aorta is exam-
ined at autopsy (shown in the image). Loss of which of
the following cellular/biochemical components of the
aortic media contributed the most to the development of
this patient’s abdominal aneurysm?

(A) Elastic fibers

(B) Fibrillin microfibrils
(C) Fibronectin glycoproteins
(D) Heparin sulfate proteoglycans
(E) Reticular fibers

6 The delicate stromal fibers described in Question 5 are

composed primarily of which of the following structural
proteins?
(A) Collagen type I
(B) Collagen type II
(C) Collagen type III
(D) Elastin
(E) Fibrillin

7 Which of the following bone marrow–derived cells is

typically found within open spaces formed by the extra-
cellular matrix fibers described in Question 5? These
cells are believed to play an important role in anticancer (A) Collagen type I fibers
immune surveillance. (B) Elastic fibers/lamellae
(A) Lymphocytes (C) Heparin sulfate proteoglycans
(B) Mast cells (D) Reticular (type III collagen) fibers
(C) Macrophages (E) Smooth muscle bundles
(D) Neutrophils
(E) Plasma cells 10 A 12-month-old boy is brought to the emergency room
for examination of his right arm following a tumble at
8 A 3-year-old girl is found to have extremely pliable skin. school. Radiologic examination of the limb reveals a
Her parents note that she bruises easily and that her recent fracture of the right ulna and evidence of several
joints can be hyperextended. Biochemical and genetic additional healing fractures. Further testing demonstrates
studies establish a diagnosis of Ehlers-Danlos syndrome. that this child has osteogenesis imperfecta, an autosomal
This patient’s genetic disease is caused by an abnormal- dominant genetic disease caused by mutations in the
ity or deficiency of which of the following proteins? gene for which of the following structural proteins?
(A) Actin (A) Collagen type I
(B) Collagen (B) Collagen type II
(C) Elastin (C) Elastin
(D) Fibrillin (D) Fibrillin-1
(E) Myosin (E) Laminin
32 Chapter 3

11 Type I collagen described in Question 10 belongs to positive for Streptococcus pyogenes. Spread of this bacte-
which subfamily of collagens? rial infection within the patient’s dermis may occur if the
intrinsic viscosity of dermal connective tissue is altered
(A) Anchoring fibril–forming collagens
by infection. Which of the following connective tis-
(B) Fibril-associated collagens
sue components determines the viscosity of connective
(C) Fibril-forming collagens tissue and provides a protective barrier that limits the
(D) Network-forming collagens spread of deep-seeded bacterial infections in the skin?
(E) Transmembrane collagens (A) Collagen type I fibers
(B) Elastic fibers
12 In patients with osteogenesis imperfecta, gene muta-
tions that change which of the following amino acids can (C) Fibroblast
block the formation of collagen triple helices? (D) Ground substance
(A) Glycine (E) Reticular (type III collagen) fibers
(B) Histidine
17 Which of the following connective tissue components
(C) Leucine binds the most water and regulates the crucial biologi-
(D) Lysine cal functions of the viscous and highly hydrated ground
(E) Proline substance described in Question 16?
(A) Elastic fibers
13 During fibrillogenesis of type I collagen, the triple helix
(B) Fibroblasts
of the procollagen molecule is formed at which of the
following locations? (C) Glycoproteins
(A) Extracellular space (D) Glycosaminoglycans
(B) Golgi apparatus (E) Proteoglycan core proteins
(C) Nucleus
18 The parents of a 3-year-old boy are concerned that their
(D) Rough endoplasmic reticulum son shows signs of physical and mental retardation.
(E) Secretory vesicles After a series of physical and laboratory examinations,
the child is diagnosed with Hurler syndrome. This rare
14 A 28-year-old marine complains of gingivitis, skin hem-
genetic disease is caused by disordered degradation and
orrhages, multiple infections, and poor wound healing.
abnormal accumulation of which of the following con-
Laboratory studies suggest vitamin C deficiency (scurvy).
nective tissue structural components?
Lack of vitamin C in this patient primarily affects which
(A) Collagen fibers
of the following essential steps in collagen fibrillogenesis?
(B) Elastic fibers
(A) Cleavage of uncoiled collagen propeptides
(C) Glycoproteins
(B) Formation of tropocollagen fibrils
(D) Glycosaminoglycans
(C) Galactosylation of hydroxylysine residues
(E) Proteoglycan core proteins
(D) Hydroxylation of proline and lysine residues
(E) Secretion of procollagen into extracellular space 19 Which of the following components of connective tissue
links cells to the extracellular matrix to help maintain
15 A 2-year-old girl with itchy skin and respiratory distress is
tissue integrity and regulate cell behavior?
brought to the emergency room by her parents 30 minutes
after eating peanut butter cookies. On physical examina- (A) Proteoglycans
tion, the patient shows flushing and swelling of her lips (B) Glycoproteins
and eyelids. Hives are present over her face and arms. Vital (C) Collagen fibers
signs are blood pressure 90/40 mm Hg and pulse 100 per (D) Elastic fibers
minute. Which of the following inflammatory cells is pri- (E) Glycosaminoglycans
marily responsible for the development of increased vascu-
lar permeability in this patient with a severe peanut allergy? 20 A 12-year-old girl has a 1.5-cm birthmark (benign con-
(A) Eosinophils genital nevus) removed from her left upper thigh under
(B) Macrophages local anesthesia. Which of the following families of cell
(C) Mast cells adhesion molecules is the principal component of the
(D) Neutrophils “provisional matrix” that mediates cell-to-matrix interac-
tions during wound healing in this patient?
(E) Plasma cells
(A) Cadherins
16 A 17-year-old boy presents with yellow and red-crusted (B) Fibronectins
lesions over his face of 5-day duration. He is a mem- (C) Integrins
ber of the high school wrestling team and has a recent (D) Laminins
history of intermittent low-grade fever. Skin cultures are (E) Selectins
 Connective Tissue 33

21 The right lower limb of a 6-year-old boy becomes swol- 24 A biopsy of the small intestine is sectioned and stained
len and enlarged following a visit to South Africa. He with H&E (shown in the image). Identify the cell indi-
is diagnosed with lymphatic filariasis. The patient’s soft cated by the arrow.
tissue swelling (edema) is caused by an accumulation of
which of the following connective tissue components?
(A) Collagen fibers
(B) Glycoproteins
(C) Glycosaminoglycans
(D) Proteoglycans
(E) Tissue fluid

22 A 65-year-old woman jogger with a history of tendonitis

affecting the pes anserinus at the knee suffers a massive
stroke and expires. A section of her left sartorius tendon
is examined at autopsy (shown in the image). This col-
lagen-rich connective tissue is important in transmitting
force from muscle to bone. Which of the following best
describes this type of connective tissue?

(A) Eosinophil
(B) Macrophage
(C) Mast cell
(D) Neutrophil
(E) Plasma cell

25 A 44-year-old woman presents with a 2-week history

of fever and painful joints. Physical examination shows
skin pigmentation, glossitis (inflammation of tongue),
and generalized lymphadenopathy. The patient has lost
9 kg (20 lb) over the past 6 months. She reports that
her stools are pale and foul smelling. Biopsy of the small
intestine is shown in the image. Identify the cells indi-
cated by the arrows.

(A) Dense irregular

(B) Dense regular
(C) Elastic
(D) Loose
(E) Reticular

23 A 48-year-old man is admitted to the hospital with a fever

of 38°C (103°F), night sweats, persistent cough, and
prolonged diarrhea. Stool culture reveals the presence
of acid-fast bacilli that are identified as Mycobacterium
avium–intracellulare. Immune responses to the pathogen
are known to involve IgA antibodies that are secreted
into the lumen of the small intestine. This immunoglob-
ulin is produced and secreted by which of the following
bone marrow–derived cells?
(A) Eosinophils (A) Eosinophils
(B) Macrophages (B) Fibroblasts
(C) Mast cells (C) Macrophages
(D) Neutrophils (D) Mast cells
(E) Plasma cells (E) Plasma cells
34 Chapter 3

26 In the image shown for Question 25, which of the following (A) Dense irregular connective tissue
types of connective tissue best describes the cellular layer (B) Hyaline cartilage
that lies below the simple columnar, lining epithelium? (C) Mesenchyme
(A) Adipose tissue (D) Nonmineralized bone
(B) Dense irregular connective tissue (E) Red bone marrow
(C) Elastic connective tissue
(D) Loose connective tissue 29 An obese, 18-year-old man (BMI = 32 kg/m2) presents
(E) Reticular connective tissue with questions regarding his weight. The patient admits
to an unusually strong appetite and uncontrolled food
27 A section of the aorta is examined at autopsy using a spe- intake. His behavior may be related to decreased serum
cial stain (shown in the image). Identify the tissue type in concentration of which of the following hormones?
the region indicated by the double arrow. (A) Cholecystokinin
(B) Ghrelin
(C) Glucagon
(D) Leptin
(E) Melatonin

30 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) Dense irregular connective tissue

(B) Dense regular connective tissue
(C) Elastic connective tissue
(D) Reticular connective tissue
(E) Smooth muscle tissue

28 A 38-year-old woman delivers a stillborn neonate with

craniofacial abnormalities at 24 weeks gestation. A sec-
tion of fetal skull is examined by light microscopy
(shown in the image). Which of the following types of
(A) Multilocular adipose tissue with cellular hyperplasia
connective tissue best describes this autopsy specimen?
(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

31 The adipocytes described in Question 30 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
 Connective Tissue 35

32 In addition to providing body insulation and maintain- 34 A 15-year-old girl suffers from anorexia nervosa. During
ing energy homeostasis, adipose tissue is considered to your physical examination of the patient, you under-
be an important organ for which of the following bio- stand that, despite inadequate nutrition, white adipose
logical functions? tissue will generally remain undiminished in mass in
(A) Calcium storage which of the following anatomic locations?
(B) Endocrine secretion (A) Breast
(C) Hematopoiesis (B) Greater omentum
(D) Immune surveillance (C) Mesentery of the small intestine
(E) Wound healing (D) Periorbital space
(E) Subcutaneous fascia
33 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 con-
centration of which of the following adipocyte-produced
hormones?
(A) Adiponectin
(B) Angiotensinogen
(C) Estrogens
(D) Leptin
(E) Resistin
36 Chapter 3

ANSWERS elastic fibers, and ground substance) are produced by

fibroblasts. Fibroblasts synthesize and secrete procol-
1 The answer is A: Dense, irregular connective tissue. Basal lagen molecules of various types, as well as precursor
cell carcinoma is the most common malignant tumor in molecules that form elastic fibers. Collagen and elastic
persons with pale skin. It usually develops on the sun- fiber assembly and packing occur in the extracellular
damaged skin of people with fair skin and freckles. In space. By contrast, elastic connective tissue compo-
this skin biopsy, dense irregular connective tissue in the nents found in large arteries and veins are produced
dermis shows coarse, randomly oriented and eosino- by smooth muscle cells. For the patient described in
philic collagen fibers and bundles with few cells. It can be Question 3, invasion of stromal connective tissue by
found in the dermis, organ capsules, and between glan- malignant cells usually incites a pronounced fibroblas-
dular tissues. Dense, regular connective tissue (choice B) tic proliferation. This “desmoplasia” creates a palpable
is characterized by coarse collagen fiber/bundles that are mass, which is the most common initial sign of ductal
regularly oriented and well organized. Glandular epithelia carcinoma of breast. Invasive ductal carcinoma usually
(choice C) are highly cellular and well organized. Skeletal manifests as a hard, fixed mass that is often referred
muscle fibers (choice D) would show a uniform distri- to as scirrhous carcinoma. On gross examination, the
bution with flattened peripheral nuclei. Smooth muscle tumor is typically firm and shows irregular margins.
fibers (choice E) would appear more cellular with abun- None of the other choices synthesizes large amounts of
dant nuclei located in the center of each muscle fiber. collagen.
Keywords: Basal cell carcinoma, dense irregular connec- Keywords: Fibroblasts, extracellular matrix
tive tissue
5 The answer is E: Reticular fibers. Reticular fibers are
2 The answer is D: Loose connective tissue. Loose connective delicate, branching fibers that form a three-dimensional
tissue is the most common connective tissue type found meshwork and supporting stroma. Reticular fibers are
throughout the body and provides support to other struc- found in highly cellular organs, such as lymph nodes,
tures (e.g., epithelial tissues, blood vessels, muscles). In spleen, liver, and pancreas. Routine H&E staining does
this skin biopsy, the tissue layer underlying the epithe- not reveal the presence of reticular fibers. Reticular
lium demonstrates characteristic features of loose connec- fibers appear black in slides treated with special silver
tive tissue. It is highly cellular and vascular and contains stains. Elastic fibers (choice A) are composed of elastin
loosely packed collagen fibers that are not identifiable by and fibrillin microfibrils (choice B), and they are best
light microscopy. Elastic and reticular fibers are present in visualized using special elastic stains. Fibronectin gly-
loose connective tissue, but the dominant fibers are col- coproteins and heparin sulfate proteoglycans (choices
lagenous. Therefore, choices C and E are incorrect. Since C and D) are components of ground substance that
the collagenous fibers are loosely packed and there are do not show fibrous features when examined by light
no or few adipocytes, choices A and B are also incorrect. microscopy.
Keywords: Basal cell carcinoma, loose connective tissue Keywords: Breast cancer, lymph nodes, reticular fibers

3 The answer is A: Dense irregular. Breast cancer is the most 6 The answer is C: Collagen type III. Small-diameter,
common malignancy of women in the United States, and branching reticular fibers are composed mainly of type
mortality from this disease among women is second only III collagen. Type I collagen (choice A) is the major com-
to that of lung cancer. In the normal portion of this breast ponent of collagenous fibers, whereas type II collagen
biopsy, the indicated area surrounds lobules of the mam- (choice B) forms fibrils in the matrix of cartilage. Elastin
mary gland. This area features densely packed collagen and fibrillin (choices D and E) are major components of
fibers oriented in different directions, with fewer cells elastic fibers or lamellae.
than in the area immediately surrounding and cushion- Keywords: Reticular fibers
ing the glandular epithelium (loose connective tissue).
It may be confusing to students that collagen fibers in 7 The answer is C: Macrophages. In lymph nodes and
a localized area may appear “regular,” particularly when spleen, macrophages reside within the sinus-like spaces
viewed at high magnification; however, when examined formed by reticular fibers. Here, they monitor material
over larger distance scales, the collagen fibers surround- that passes through the organ. Pathogens and malignant
ing breast lobules are irregular. Therefore, choices B, C, cells are captured and phagocytosed by macrophages that
D, and E are incorrect. reside in regional lymph nodes. Lymphocytes (choice A)
Keywords: Breast cancer, dense irregular connective form the parenchyma of lymph nodes. Plasma cells
tissue (choice E) and neutrophils (choice D) may be present
in lymph nodes, but they are not specifically associated
4 The answer is B: Fibroblasts. For collagenous connec- with reticular fibers. Mast cells (choice B) are typically
tive tissues present in skin and tendon, all of the com- found in loose connective tissue.
ponents of the extracellular matrix (e.g., collagen fibers, Keywords: Macrophage, lymph node
 Connective Tissue 37

8 The answer is B: Collagen. Ehlers-Danlos syndrome Therefore, these collagens comprise a fibril-forming sub-
(EDS) is a group of rare, autosomal dominant, inherited family (fibrillar collagens). Fibril-associated collagens
disorders of connective tissue that feature remarkable (choice B), such as types XII and XIV, have interruptions
hyperelasticity and fragility of the skin and joint hyper- in their triple helices; they associate with the surface of
mobility. The common feature of most types of EDS is collagen fibrils and regulate fibril assemble. Some col-
a generalized defect in collagen, including abnormali- lagens, for example, type VII, form anchoring fibrils
ties in its molecular structure, synthesis, secretion, and (choice A) that bind the basal lamina to the underlying
degradation. Patients typically can stretch their skin connective tissue. Network-forming collagens (choice
many centimeters, and trivial injuries can lead to seri- D) create complex networks, such as type IV collagen in
ous wounds. Because sutures do not hold well, dehis- basement membranes, type VI collagen forming a peri-
cence of surgical incisions is common. Hypermobility cellular filamentous network in cartilage, and type VIII
of the joints allows unusual extension and flexion. and X collagen networks in tissues. Transmembrane col-
Abnormalities would not be expected in the other cell/ lagens (choice E), such as types XVII and XIII, link cells
tissue components listed. with extracellular matrix glycoproteins.
Keywords: Ehlers-Danlos syndrome Keywords: Collagens

9 The answer is B: Elastic fibers/lamellae. Aneurysms are 12 The answer is A: Glycine. To form a collagen triple helix,
localized dilations of blood vessels caused by a congeni- every third amino acid in each of the three procollagen
tal or acquired weakness. An aneurysm is defined as an α-chains must be glycine. Other amino acids can occur
increase in the vessel’s diameter by at least 50%. Forms in the other two positions, but the most abundant amino
of aneurysm include saccular, fusiform, and dissecting acids in collagen are hydroxyproline and hydroxylysine.
(tear in the media). The large majority of aneurysms of A gene mutation involving glycine at the third position
the abdominal aorta in elderly patients are related to ath- will affect the formation of the triple helix and block the
erosclerosis. The aneurysm in this patient was opened synthesis and deposition of collagen fibrils/fibers.
longitudinally to reveal a large mural thrombus within the Keywords: Collagens, osteogenesis imperfecta
lumen (see photograph). Loss of internal and external elas-
tic fibers/lamina in the aortic wall is associated with aortic 13 The answer is D: Rough endoplasmic reticulum. Formation
dilation and increased risk of rupture. Loss or deficiency of of type I collagen fibers in connective tissue involves
the other components is not believed to play a direct role intracellular procollagen synthesis, as well as extracel-
in the pathogenesis of abdominal aortic aneurysm. lular assembly of collagen molecules into fibrils and
Keywords: Aneurysm, elastic lamellae/fibers fibers. The procollagen α-chains are synthesized and
further modified in the rough endoplasmic reticulum
10 The answer is A: Collagen type I. Mutations in the type I (rER) through a series of posttranslational modifica-
collagen gene cause a deficiency in the synthesis of type I tions, including, but not limiting to (1) hydroxylation
collagen and abnormal fibrillogenesis. Well-organized col- of proline and lysine residues, (2) cleavage of the signal
lagen fibers are the principal organic component of bone. peptide from the pro-α-chains, and (3) glycosylation of
They provide bone with flexibility. Brittle bones and fre- specific hydroxylysine residues. The modified pro-α-
quent fractures are common complaints in patients with chains form triple helical procollagen molecules that are
osteogenesis imperfecta. Mutations affecting type II colla- further stabilized by hydrogen and disulfide bonds in the
gen (choice B) are associated with Kniest dysplasia or type rER. Procollagen molecules are then transported into the
2 achondrogenesis (cartilage abnormalities). Mutations Golgi apparatus (choice B), where they are packed into
affecting fibrillin-1 (choice D) cause Marfan syndrome secretory vesicles (choice E) and secreted into the extra-
(defective elastic fiber formation). Mutations affecting elas- cellular space (choice A).
tin (choice C) would cause vascular disorders. Laminins Keywords: Collagen, posttranslational modifications
(choice E) are a family of adhesive glycoproteins in the
extracellular matrix. Mutations in the laminin beta-2 gene 14 The answer is D: Hydroxylation of proline and lysine resi-
are associated with Pierson syndrome, a congenital dis- dues. Intra- and interchain hydrogen bonds, disulfide
ease with neurological, renal, and ocular deficits. bonds, and chaperone proteins are all essential for the
Keywords: Osteogenesis imperfecta formation of the triple-helical structure of procollagen.
Hydroxyl groups added to proline and lysine residues
11 The answer is C: Fibril-forming collagens. Collagen is a during posttranslational processing provide the struc-
protein superfamily composed of at least 27 types. Based tural basis for hydrogen bonding. Vitamin C (ascorbic
on their structural and amino acid similarities, colla- acid) is an essential cofactor for enzymes that regulate
gens are divided into several subfamilies. Type I colla- hydroxylation of proline and lysine. These enzymes are
gen, as well as collagen types II, III, V, and XI contain lysyl hydroxylase and prolyl hydroxylase. Vitamin C
uninterrupted glycine–proline–hydroxyproline repeats, deficiency causes defects in the formation of triple heli-
and their triple-helical molecules assemble into fibrils. cal procollagen, and this results in poor wound healing.
38 Chapter 3
Skin hemorrhages arise from capillaries that have weak are highly negatively charged, and they attract/retain a
walls and are easily damaged by minor trauma. Impaired large volume of water. This hydrated gel lubricates tis-
collagen synthesis also leads to gingivitis and alveolar sues and absorbs shock. GAGs bound to core proteins
bone resorption, which may lead eventually to loss of form large macromolecular structures termed proteo-
teeth. None of the other biochemical steps in collagen glycans. Whereas GAG chains retain large amounts of
fibrillogenesis are affected by vitamin C deficiency. water, the core proteins of proteoglycans (choice E) do
Keywords: Scurvy, vitamin C deficiency not bind water. Glycoproteins (choice C) contain mul-
tivalent domains that interconnect and stabilize cells
15 The answer is C: Mast cells. Antigens binding to receptors within the extracellular matrix. Fibrous components and
on the surface of mast cells trigger the release of inflam- cells (choices A and B) are not involved directly in regu-
matory mediators such as histamine. Release of this vaso- lating the viscosity of ground substance.
active mediator from stored mast cell granules causes an Keywords: Ground substance
immediate hypersensitivity reaction. The other cells are
involved in inflammation, but they do not initiate imme- 18 The answer is D: Glycosaminoglycans. Hurler syndrome
diate hypersensitivity. Eosinophils (choice A) are involved is a rare genetic disorder characterized by excess accumu-
in the defense against parasitic infestations. Macrophages lation of glycosaminoglycans in tissue. Highly glycosylated
and neutrophils (choices B and D) respond to cell injury. proteoglycans are constantly synthesized and degraded
They internalize debris and pathogens via phagocytosis. within lysosomes. Deficiency of these crucial lysosomal
Macrophages also “present” foreign antigens to lympho- enzymes blocks substrate degradation and leads to intra-
cytes to initiate immune responses. Plasma cells (choice cellular accumulation of glycosaminoglycans. Symptoms
E) synthesize and secrete immunoglobulin (antibody). of these “mucopolysaccharidoses” depend on the particu-
Keywords: Peanut allergy, type 1 hypersensitivity reaction lar enzyme that is deficient. In Hurler syndrome, defi-
ciency of alpha-L-iduronidase causes heparan sulfate and
16 The answer is D: Ground substance. Ground substance dermatan sulfate to accumulate in various tissues and
is a highly hydrated, transparent mixture of macromol- organs. Hurler syndrome presents in early childhood,
ecules occupying the extracellular space located between and patients may die at young age.
cells and fibrous components of the connective tissue. Keywords: Hurler syndrome, glycosaminoglycans
This complex mixture of macromolecules is viscous and
serves to lubricate joints and internal organs. Due to its 19 The answer is B: Glycoproteins. Glycoproteins are secreted
high viscosity, ground substance can also serve as a bar- molecules that contain linear or branched N-linked and
rier to invading bacteria and other microorganisms and O-linked oligosaccharides. Adhesive glycoproteins of the
helps prevent them from spreading by lateral diffusion extracellular matrix possess binding domains for collagen
into adjacent tissues. However, some bacteria secrete fibrils, proteoglycans, GAGs, and other glycoproteins.
hyaluronidase, an enzyme that degrades proteoglycans. These glycoproteins also contain binding sites for cells
This enzyme significantly reduces the viscosity of ground and interact with cell surface receptors (e.g., integrins).
substance, enabling hyaluronidase-positive bacteria to These multiadhesive features enable glycoproteins to link
be more invasive. Impetigo in this patient represents a cells and tissues to extracellular matrix to maintain tissue
localized, intraepidermal infection with S. pyogenes. It integrity. They also provide signals for cell proliferation
spreads by close contact and most commonly affects and cell migration. None of the other components exhibit
children. Minor trauma allows inoculation of bacteria. multiple binding domains that link cells to the matrix.
The intraepithelial pustule that forms will eventually Keywords: Glycoproteins
rupture and leak a purulent inflammatory exudate.
Keywords: Impetigo, ground substance 20 The answer is B: Fibronectins. Fibronectins are per-
haps the most abundant multiadhesive glycoproteins in
17 The answer is D: Glycosaminoglycans. Proteoglycans, gly- the extracellular matrix of connective tissues. Plasma-
cosaminoglycans, and glycoproteins are the three major derived fibronectin is also deposited at sites of tissue
groups of macromolecules found in the ground sub- injury to facilitate wound healing. During the initial
stance of connective tissue. Glycosaminoglycans (GAGs) phase of healing, fibronectin in the extravasated plasma
are linear heteropolysaccharides formed by repeating is cross-linked to fibrin, collagen, and other extracellular
disaccharide units. GAGs are categorized into seven matrix components by the action of transglutaminases.
distinct groups based on their specific sugar residues This cross-linking provides a provisional stabilization of
and degree of sulfation. These groups include hyaluro- the wound during the first several hours and provides
nan, chondroitin-4-sulfate and chondroitin-6-sulfate, a substrate for cell adhesion and migration. Cadherins
dermatan sulfate, keratan sulfate, heparan sulfate, and (choice A) and integrins (choice C) are cell–cell adhesion
heparin. The largest and most ubiquitous GAG is hyal- molecules. Like the selectin family of cell adhesion pro-
uronic acid. The carbohydrate chains of this polyanion teins, they are found at the cell surface and are not part of
typically contain thousands of monosaccharides. GAGs the extracellular matrix. Laminins (choice D) are present
 Connective Tissue 39
in basement membranes. Selectins (choice E) are sugar- antibodies that target invading pathogens for destruction.
binding glycoproteins that mediate the initial attachment None of the other inflammatory cells secrete antibodies.
of leukocytes to endothelial cells at sites of inflammation. Keywords: Acquired immunodeficiency, plasma cells
Keywords: Nevus, wound healing
24 The answer is E: Plasma cell. Plasma cells are considered
21 The answer is E: Tissue fluid. A small amount of tissue to be immigrant cells that migrate from the vascular space
fluid is normally retained in extracellular/interstitial space. into connective tissues. In routine H&E-stained sections,
This fluid is similar in ion composition to blood plasma. the nuclei of mature plasma cells display a characteristic
In certain pathologic conditions, fluid passes through the “clock-face” or “cartwheel” appearance with a prominent,
capillary wall and accumulates in the tissue resulting in centrally located nucleolus and clumps of heterochroma-
soft tissue edema. Conditions associated with general- tin along the periphery of the nucleus. Plasma cell cyto-
ized edema include lymphatic obstruction secondary to plasm is typically basophilic, owing to an abundance of
filarial infestations of regional lymph nodes; decreased rER that facilitates active protein synthesis. An extensive
venous return to the heart due to congestive heart dis- Golgi apparatus may also be seen as a pale-stained area
ease; increased capillary hydrostatic pressure; and loss in close proximity to the nucleus. None of the other cells
of plasma protein (reduced oncotic pressure). Filariasis exhibit cytologic features of plasma cells.
is caused by infestation of filarial nematodes that reside Keywords: Plasma cells
in lymphatic vessels and lymph nodes, thereby causing
lymphatic obstruction and lymphedema. Severe and mas- 25 The answer is C: Macrophages. Whipple disease is a rare
sive lymphedema is referred to as elephantiasis. Filariasis infectious disorder of the small intestine in which mal-
is common in Africa and South Asia. absorption is the most prominent feature. The disorder
Keywords: Filariasis, edema typically features infiltration of the small bowel mucosa
by macrophages that are packed with small, rod-shaped
22 The answer is B: Dense regular. Dense regular connective bacilli (Tropheryma whippelii). Infiltrates of macrophages
tissue is found in tendons and ligaments, where coarse containing bacilli may be found in other organs, includ-
strong collagen fibers are organized into regularly ori- ing the lymph nodes and heart. Macrophages bind and
ented, parallel bundles. Elongated fibroblasts are located internalize pathogens and necrotic tissue debris. As seen
in spaces that are parallel to the collagen fibers. In longi- in the image, macrophages are large cells with eosino-
tudinal sections of tendon (shown in the image), fibro- philic cytoplasm containing phagocytosed material.
blast nuclei appear as linear dark lines interspersed with Plasma cells are identified with arrowheads (shown in
collagen bundles. The cytoplasm of fibroblasts cannot be the image). None of the other cells are phagocytes.
distinguished from collagen in H&E slide preparations. Keywords: Whipple disease, macrophages
The organization of collagen fibers in dense regular con-
nective tissue serves to resist forces generated in the 26 The answer is D: Loose connective tissue. The lamina
same direction, in response to stress. As a result, dense propria is a cellular layer of loose connective tissue that
regular connective tissue is adapted to transmit force underlies the lining epithelium of the gastrointestinal
from muscle to bone in tendons or transmit force from (GI) tract. Loosely packed collagen fibers and some
bone to bone in ligaments. Dense regular connective tis- elastic fibers are present in the lamina propria, but they
sue exhibits a small amount of ground substance and few are not readily apparent in routine H&E-stained prepa-
cells or vessels. None of the other types of connective rations. The lamina propria of the GI tract contains an
tissue exhibit histologic features of tendon. abundance of cells, including numerous capillaries and
Keywords: Tendons, dense regular connective tissue lymphatic vessels (shown in the image). None of the
other types of connective tissue describes histologic fea-
23 The answer is E: Plasma cells. M. avium and M. intracel- tures of the lamina propria.
lulare are similar mycobacterial species that cause identical Keywords: Loose connective tissue, lamina propria
diseases and are, therefore, classified together as M. avium–
intracellulare complex (MAC). MAC is a rare, granuloma- 27 The answer is C: Elastic connective tissue. Elastic connective
tous, pulmonary disease in immunocompetent persons, tissue is found in large elastic arteries and some ligaments
but it is a progressive systemic disorder in patients with along the vertebral column (e.g., ligamentum flavum). In
AIDS. One-third of all AIDS patients develop overt MAC some tissues, elastic fibers (ligamentum flavum) or elastic
infections. The proliferation of organisms and the recruit- lamellae (large arteries) comprise the predominant extra-
ment of macrophages produce expanding lesions, ranging cellular structural component. Collagen fibers/bundles are
from epithelioid granulomas containing few organisms to also present, but they are far less abundant than in collag-
loose aggregates with foamy macrophages. Plasma cells are enous connective tissue. In the tunica media (the middle
located in various locations throughout the body includ- layer of large arterial walls), layers of smooth muscle fibers
ing the lamina propria of the gastrointestinal tract. Plasma (choice E) are found between elastic lamellae and colla-
cells (derived from B lymphocytes) produce soluble gen fibers. In most types of connective tissue, fibroblasts
40 Chapter 3
synthesize the extracellular components; however, smooth found in newborns. Unilocular adipose tissue with cellular
muscle cells synthesize the connective tissue found in large hyperplasia (choice C) occurs in early childhood but does
elastic arteries (elastic lamellae, collagen fibers, and ground not contribute to the pathogenesis of adult obesity.
substance). None of the other connective tissues listed fea- Keywords: Obesity, adipose tissue
ture elastic fibers/lamellae as a major structural component.
Keywords: Elastic connective tissue 31 The answer is C: Reticular fibers. Adipocytes synthesize
and secrete reticular (type III collagen) fibers that form
28 The answer is C: Mesenchyme. Mesenchyme is embry- an interwoven network that provides support. These
onic primitive connective tissue that gives rise to all the reticular networks are only visible using special stains.
adult connective tissue types. Muscle tissues, vascular, They are invisible by H&E staining. The meshwork of
and urogenital systems are also derived from embryonic polygonal strands seen in the image shown in Question
mesenchyme. In a routine H&E preparation, mesenchy- 30 consists of the cytoplasm of two adjacent adipocytes
mal cells appear small and spindle shaped. Fine, delicate, and the thin layer of the extracellular matrix that is
and sparse collagen fibers are scattered between the cells. located between them. Rich supply of blood vessels and
Undifferentiated mesenchymal cells may be present in nerves are found in the extracellular spaces between the
adult connective tissue, but they cannot be distinguished crowded adipocytes. Elastic fibers and collagen fibers
from fibroblasts on H&E staining. The other tissues are are also present in the extracellular matrix between adi-
examples of adult connective tissue, and they do not pocytes, but unlike reticular fibers, they do not form an
describe histological features of embryonic mesenchyme. interwoven network. Skeletal and smooth muscle fibers
Keywords: Mesenchyme (choices D and E) are not found in white adipose tissue.
Keywords: Obesity, adipocytes
29 The answer is D: Leptin. Leptin is a 16-kD polypeptide
hormone produced by adipocytes in white adipose tis- 32 The answer is B: Endocrine secretion. A variety of hormones,
sue. It acts on leptin receptors in the hypothalamus to growth factors, and cytokines are produced in white adi-
regulate food intake and energy use. Unlike short-term pose tissue. Leptin (discussed earlier in this chapter) is
weight control hormones, such as peptide YY, inhibition a polypeptide hormone secreted by adipocytes that helps
of appetite by leptin has a long-term effect on weight. regulate food intake and body weight control. Therefore,
Absence or decreased serum levels of leptin result in adipose tissue is not only an organ for energy storage; it
uncontrolled food intake and obesity. Cholecystokinin also serves as an endocrine organ. Adipose tissue does
(choice A) is secreted by mucosal epithelial cells of the not regulate the other biological functions listed.
small intestine and regulates digestion in the small intes- Keywords: Adipose tissue
tine by stimulating the release of digestive enzymes and
bile. Glucagon (choice C) is secreted by the pancreas 33 The answer is B: Angiotensinogen. Adipocytes produce
and raises blood glucose levels. Together with insulin, the polypeptide hormone, angiotensinogen (AGE). This
glucagon helps maintain stable levels of blood glucose. hormone is also secreted by other tissues/organs (e.g.,
Melatonin (choice E), secreted by the pineal gland, reg- liver). Over production of AGE is associated with sys-
ulates the rhythmic sleep–wake cycle. Ghrelin (choice temic hypertension. For this reason, obese individuals
B) is produced by the small intestine and functions as commonly suffer from systemic hypertension. None of
a “meal initiator” by stimulating the sense of hunger. the other adipocyte-produced hormones regulates sys-
Overproduction of ghrelin in patients with Prader-Willi temic blood pressure.
syndrome can cause compulsive eating and obesity. Keywords: Obesity, systemic hypertension
Keywords: Obesity
34 The answer is D: Periorbital space. White adipose tis-
30 The answer is D: Unilocular adipose tissue with cellular hyper- sue found throughout the body functions as an organ
trophy. In white adipose tissue, adipocytes are large, for energy storage, insulation, cushioning, and hormone
crowded, polyhedral cells. The cells are filled with one sin- secretion. When caloric intake is reduced, as in this case
gle droplet of lipid (i.e., unilobular cells). The cytoplasm of anorexia nervosa (a disorder with irrational fear of
and nucleus are pushed to the periphery of the cell. In gaining weight and extreme restriction of food), lipids
routine histological preparations, lipid extraction during within adipocytes are broken down and mobilized to
tissue processing causes adipocytes to assume a signet ring provide energy. White adipose tissue in most regions of
profile. Excessive energy intake with less energy expendi- the body (choices A, B, C, and E) is depleted of lipid.
ture results in obesity, with a significant accumulation of However, white adipose tissue in certain parts of the
adipose tissue. In childhood, obesity results from increases body (e.g., beneath the epicardium, in the periorbital
in the size (hypertrophy) of adipocytes, as well as the for- space, in the palms of the hands, and in soles of the feet)
mation of new adipocytes (hyperplasia). In adults, obesity remain largely undiminished during long periods of star-
principally involves accumulation of lipid within exist- vation, so as to maintain cushioning functions in these
ing adipocytes (hypertrophy). Multilocular adipose tissue critical areas.
(choices A and B), termed brown adipose tissue, is mainly Keywords: Anorexia nervosa