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ACVP Phase II Exam - Anatomic Pathology > Bones and Joints > Flashcards

Bones and Joints Flashcards

1
Q 
Primitive osteoprogenitor cells of mesenchymal origin develop into all of the following cell types in bones except:
A. osteoblasts
B. osteocytes
C. lining cells
D. osteoclasts
A

D. osteoclasts. Osteoclasts are derived from hematopoietic stem cells of the macrophage line

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2
Q

Which transcription factor guides development of mesenchymal cells into osteoprogenitor cells?

A

Runx2 ( runt-related transcription factor 2)

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3
Q

SOC5, 6 and 9 are responsible for development of which cell type?

A

Chondrocytes

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4
Q

PPAR-gamma2 (peroxisome proliferator activator receptor) is responsible for development of which cell type?

A

Adipocytes

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5
Q

Osteoblasts develop under signaling from which transcription factors?

A

Runx2, osterix, beta-catenin

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6
Q

Functional roles of osteoblasts include?

A

manufacturing osteoid, initiate mineralization, mediate both bone resorption and formation, produce regulatory factors deposited in the bone matrix

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7
Q

Bone lining cells are inactive versions of what cells?

A

osteoblasts

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8
Q

Which type of bone cell is responsible for lining the endosteal surface of bone and forming the functional barrier between the extracellular fluid compartment of bone tissue and surrounding tissues?

A

bone lining cells, most abundant cell type in the endosteal skeleton. Form barrier between osteoclasts precursors and bone surface.

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9
Q

What cells are responsible for the bone-blood barrier, controlling the movement of ions in and out of the extracellular fluid?

A

bone-lining cells

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10
Q

What is an osteoblast marker expressed by bone-lining cells during active remodeling?

A

RANKL ( receptor activator of nuclear factor kappa B ligand)

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11
Q

When does an osteoblast become and osteocyte?

A

When it surrounds itself with osteoid and resides in lacunae in the mineralized matrix

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12
Q

How do osteocytes maintain contact with other osteocytes, osteoblasts and bone-lining cells?

A

Through a network of branching cytoplasmic processes called canaliculi

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13
Q

What key regulatory factors for bone resorption and formation are produced by osteocytes?

A

sclerostin, RANKL, fibroblast growth factor 23 (FGF23), All produced under control of PTH

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14
Q

What is the function of increased RANKL expression by osteocytes?

A

Osteoclastic bone resorption

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15
Q

What is the function of FGF23 expression by osteocytes?

A

phosphate homeostasis –> phosphate excretion from the kidney

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16
Q

What are the key factors involved in osteoclast formation?

A

macrophage colony stimulating factors and RANK (not RANKL - that’s produced by osteoblasts and osteocytes). RANKL from osteoblasts/cytes allows fusion of osteoclast precursors to form the mature osteoclast.

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17
Q

IHC for which antigen can be useful to identify osteoclasts?

A

TRAP (tartrate resistant acid phosphatase)

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18
Q

Howship’s lacunae are shallow pits on bone surfaces containing what?

A

mature osteoclasts. Their presence indicates previous resorption even if the osteoclast is gone.

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19
Q

What factors can enhance osteoclast survival?

A

Inflammatory cytokines like TNF-a and IL-1 as well as PTH. Explains why osteoclasts are found within medullary spaces filled with fibrous tissue

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20
Q

What type of collagen is found in bone?

A

Type I collagen. Also the main collagen found in tendons, ligaments, ocular sclera and dentin

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21
Q

The enzyme lysyl oxidase which is responsible for the intermolecular cross-links in collagen, form with the assistance of what mineral?

A

Copper

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22
Q

What noncollagenous protein is produced by osteoblast, found in bone and is responsible for interacting with both type I collagen and hydroxyapatite?

A

Osteonectin or SPARC. May be important in intramembranous bone formation post-fracture

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23
Q

The production of osteocalcin (or bone-Gla protein) by osteoblasts is dependent on what vitamin? What vitamin causes an increase in its synthesis?

A

dependent on Vitamin K, Vitamin D increases synthesis

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24
Q

What is the function of osteocalcin in bone formation?

A

when carboxylated, osteocalcin is deposited in osteoid before mineralization and allows strong binding to calcium

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25
Q

What are four noncollagenous proteins found in bone?

A

Osteonectin, osteocalcin, osteopontin and bone sialoprotein

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26
Q

What kinds of mineral does bone contain?

A

Ca, Phosphate, carbonate, magnesium, sodium, zinc, flouride

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27
Q

What protein is associated with ectopic bone mineralization?

A

matrix Gla-protein

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28
Q

What structures composed of extracellular organelles originating from cytoplasmic blebs from osteoblasts, chondrocytes, and odontoblasts are responsible for initiating the mineralization process?

A

matrix vesicles

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29
Q

What is the key event in the initiation of mineralization?

A

Alteration in the phosphate to inorganic pyrophosphate ratio through the enzymes ALP and ENPP1 (inorganic pyrophosphate and osteopontin normally inhibit mineralization). Upregulation of ALP is most important, increased phosphate.

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30
Q

Osteoid becomes mineralized approximately how many days after deposition?

A

5-10 days, results in the osteoid seam which is separated from mineralized bone by a basophilic linear mineralization front

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31
Q

What is woven bone characterized by ultrastructurally?

A

collagen fibers arranged in a haphazard, interwoven fashion

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32
Q

Wnt signaling is involved in which types of skeletal development?

A

All - craniofacial, limb, joint

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33
Q

Suture formation in the skull bones is regulated by which transcription factors?

A

FGFR1, 2, 3; TGF-beta1,2,3;

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34
Q

During endochondral ossification, the developing fetus chondrocytes are controlled by which transcription factor?

A

SOX9

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35
Q

What are the 3 zones of hyaline cartilage at the growth plate?

A

Reserve (i.e. resting) zone, proliferative zone, zone of hypertrophy

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36
Q

What type of collagen is found within cartilage of the resting zone?

A

Type II collagen

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37
Q

What zone of cartilage does mineralization occur?

A

The deepest part of the zone of hypertrophy

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38
Q

What structure is responsible for increasing the diameter of the physis during growth?

A

The ossification groove of Ranvier, contains progenitor cells

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39
Q

The lattice of trabeculae with a basophilic core of mineralized cartilage covered by a thin, eosinophilic layer of bone is termed?

A

primary spongiosa

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40
Q

Osteoclast formation is regulated by which 3 pathways?

A

RANK/RANKL - stimulates osteoclast formation; Wnt-betacatenin - stimulated osteoclast formation; Jagged 1/Notch 1 - inhibits osteoclast formation

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41
Q

What ratio is important in regulating osteoclast formation?

A

The ratio of RANKL to OPG (osteoprotegerin) which is a decoy of RANK. The RANKL-RANK binding (as well as some inflammatory conditions not associated with RANK/RANKL) is what leads to osteoclast production.

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42
Q

Pathogenesis of bone resorption

A

bone lining cells retract from the endosteal surface of bone, secrete enzymes to digest unmineralized bone and expose mineralized bone –> osteocyte apoptosis secondary to mechanical stress lead neighboring osteocytes to express RANKL and M-CSF–> sclerostin from osteocytes inhibits osteoblasts –> osteoclast precursors are recruited from RANKL/M-CSF –> differentiate into osteoclasts and resorb bone, then undergo apoptosis –> pre-osteoblasts are recruited, secrete PTHrP to stimulate differentiation and suppress apoptosis –> Wnt-B-catenin, BMPs and TGF-beta stimulate bone formation, mineralization and quiescence.

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43
Q

What is the difference between a resting cement line and a reversal line?

A

Resting cement line is a site where bone formation ceased for awhile then started again, whereas reversal lines are sites where bone resorption actually occurred and now bone formation has restarted

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44
Q

What is the most sensitive clinical pathology marker of bone formation?

A

Plasma osteocalcin, it is proportional to the rate of osteoid synthesis.

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45
Q

What markers are used for bone resorption?

A

tartrate-resistant acid phosphatase isoform 5b (TRAP 5b) and several breakdown products of Type I collagen : serum carboxyterminal telopeptide of type I collagen (ICTP), urinary hydroxyproline, pyridinoline (PYD), deoxypyrodinoline (DPD).

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46
Q

What are apophyses?

A

Growth plates subjected to primarily traction forces, consist of fibrocartilage. Example is the lesser trochanter of the femur.

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47
Q

What are common causes of angular limb deformities in foals?

A

Physiologic, hypothyroidism, sepsis

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48
Q

What does Codman’s triangle refer to?

A

A cone-shaped region of new bone beneath the periosteum that occurs in cases of osteosarcoma and osteomyelitis

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49
Q

Multiple microfractures involving several adjacent trabeculae without gross displacement of the bone ends are referred to as?

A

infractions; seen in bones weakened by disease that still bear weight

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50
Q

What is the most common site of a stress fracture in young racehorses?

A

dorsal or dorsomedial cortex of the 3rd metacarpal (cannon bone)

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51
Q

What is the histologic feature of a bucked shin in a horse and what breeds of horses are most affected?

A

Smoothly contoured foci of periosteal new bone on the dorsal surface of the cannon bone. QH and Thoroughbreds (racing breeds)

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52
Q

What condition is linked to bucked shins in horses and may be a sequela?

A

Saucer (incomplete) fractures of the dorsal cortex of the cannon bone.

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53
Q

Osteogenesis imperfecta is a disorder of what type of collagen?

A

Type I collagen, characterized by osteopenia and excessive bone fragility

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54
Q

Chondrodysplasias result in what type of dwarfism?

A

disproportionate

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55
Q

Dexter bulldog calves result from homozygosity of a gene with what type of expression pattern? What is the gene associated with Dexter calf chondrodysplasia?

A

incomplete dominance; ACAN (aggrecan) gene

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56
Q

What is the histologic feature of the physis in a Dexter bulldog calf?

A

lack of a distinct growth plate with densely packed chondrocytes showing no orderly arrangement into columns and a fibrillar eosinophilic intercellular matrix surrounding large vascular cartilage canals. No distinct primary or secondary spongiosa.

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57
Q

What are the four subtypes of chondrodysplasia in cattle?

A

Bulldog, Telemark, “snorter” and long-headed

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58
Q

Holsteins with bulldog chondrodysplasia have parents that are phenotypically normal. True/false

A

True. The parents are heterozygous and the gene is an autosomal recessive pattern of inheritance.

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59
Q

What is the histologic difference between snorter dwarfism and bulldog dwarfism?

A

In snorter dwarfism, the growth plate has three distinct zones but they are all shorter and more irregular with fewer hypertrophied chondrocytes

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60
Q

What breeds of sheep are susceptible to spider lamb syndrome?

A

Suffolk and Hampshire

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61
Q

What is the histologic feature of spider lamb syndrome?

A

Multiple, irregular, small ossification centers surrounded by persistent bands of cartilage

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62
Q

What is the mutation in spider lamb syndrome?

A

Point mutation in FGFR3, expressed in resting and proliferating chondrocytes and limit # of chondrocytes that enter hypertrophy phase

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63
Q

What type of disproportionate chondrodysplasia in sheep leads to chondrolysis which coalesce to form clefts and cystic spaces surrounded by concentric rings of granular and basophilci fibrillar matrix in areas of both articular and physeal cartilage?

A

Texel sheep

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64
Q

Mutations in the ACAN gene have shown to result in chondrodysplasia in what two species?

A

cattle and miniature horses

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65
Q

What breeds of dogs have pathologic chondrodysplastic syndromes?

A

Alaskan malamute, norwegian elkhound, karelian bear dog, English pointer, Great pyrenees

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66
Q

Osteogenesis imperfecta types 1 through 4 is a mutation in which genes? What is the pattern of inheritance?

A

COL1A1 or COL1A2 (code for a1 and a2 chains of Type i collagen respectively); autosomal dominant

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67
Q

Osteogenesis imperfecta is most common in what 2 species?

A

cattle and sheep

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68
Q

What is the histologic feature of osteogenesis imperfecta?

A

basophilic spicules of woven bone and minimal compaction by the addition of lamellar bone interspersed with loose mesenchymal tissue

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69
Q

What is the defect in Belgian blue cattle with dermatosparaxis?

A

deficiency in enzyme that converts procollagen to collagen, results in SKIN FRAGILITY not found in OI cases.

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70
Q

This disease, otherwise known as marble bone disease, is characterized by defective osteoclast bone resorption and dense, unresorbed cones of primary spongiosa in the bone marrow that extends from the metaphysis to the center of the diaphysis

A

Osteopetrosis

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71
Q

Osteoclasts are normally present in [low/normal/abundant/all of the above] numbers in osteopetrosis.

A

All of the above. The defect in some disorders is in the inability of osteoclasts to resorb bone due to a defective proton pump or chloride channel mutation that interfere with acidification of osteoclasts. The defect in other disorders is in RANKL which guides differentiation of osteoclasts leading to reduced #’s of osteoclasts.

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72
Q

What breed of cattle is most affected by osteopetrosis?

A

Angus. The gene in red Angus is SLC4A2 which helps acidify the osteoclast. Not in black Angus.

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73
Q

What is a hematopoietic sequelae of osteopetrosis?

A

extramedullary hematopoiesis in the liver

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74
Q

Are growth plates normal or abnormal in osteopetrosis?

A

Normal. The defect is in the metaphysis and diaphysis.

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75
Q

Osteopetrosis is associated with which viral diseases?

A

BVDV, feline leukemia virus, canine distemper virus

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76
Q

Radiating trabeculae of bone extending from the cortical bone to a thickened periosteum is the histologic feature of what disease?

A

congenital hyperostosis in piglets

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77
Q 
Which of the following bones are most affected by congenital hyperostosis?
A. humerus
B. radius
C. vertebral body
D. mandible
A

B. The radius and ulna are the most affected bones in congenital hyperostosis in piglets. The axial skeleton is not affected at all in C.H.

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78
Q

Schistosomus reflexus comprises all of the following congenital defects except:
A. lordosis
B. dorsal reflection of the limbs and pelvic bones
C. pectus excavatum
D. nonunion of the pelvic symphysis

A

C. pectus excavatum is not a classic component of schistosomus reflexus

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79
Q

Defective closure of the dorsal vertebral laminae in a section of the vertebral column results in what congenital defect?

A

spina bifida

80
Q

Which lysosomal storage diseases result in skeletal malformations?

A

mucopolysaccharidoses, mucolipidoses, gangliosidoses

81
Q

Which of the following is the deficient enzyme in mucopolysaccharidosis Type I?

A

alpha-L-iduronidase

82
Q

Mucopolysaccharidosis Type III results in what presentation of disease?

A

neurologic disease as a result of stored heparan sulfate

83
Q

Lack of metachromatic granules in neutrophils is a feature of what disease?

A

Mucopolysaccharidosis Type I

84
Q

Deficiency in alpha-neuraminidase and beta-galactosidase characterizes what disease?

A

GM1 gangliosidosis

85
Q

Congenital porphyria is distinguished from acquired porphyria by the presence of pigment in what tissues?

A

teeth and sites of older mineralization (where porphyrin hasn’t had a chance to be deposited yet)

86
Q

Porphyria may be cause by all of the following except”
A. deficiency of uroporphyrin III cosynthetase (UROS)
B. lead
c. organochlorine insecticide toxicity
d. mutation on the hydroxymethylbilane synthase gene (HMBS)
e. all of the above

A

e. all of the above can cause porphyria

87
Q 
Calcium available for metabolism in the body is found in the form of :
A. ionized Calcium
B. albumin-bound calcium
C. calcium citrate
D. calcium phosphate
A

A. ionized calcium makes up about 50% of the calcium available in the extracellular fluid and is controlled by the actions of PTH, vitamin D and calcitonin.

88
Q

What receptors detect low serum ionized calcium and respond by causing an increase in PTH?

A

calcium-sensing receptors on chief cells within the parathyroid gland

89
Q

PTH has what affect on the renal tubules?

A

binds to PTHR1 receptor and allows for increased Ca2+ resorption from the renal filtrate; also allows for decreased resorption of phosphorus from the filtrate

90
Q

What is the activity of PTH on bone in high doses?

A

Increases expression of RANKL by osteoblasts which allows recruitment and differentiation of osteoclasts to resorb bone, raising calcium and phosphorus in the blood.

91
Q

What stimulates enzymatic change of 25 hydroxyvitamin D to calcitriol (1,25 dihydroxyvitamin D3)?

A

PTH stimulates renal alpha-1-hydroxylase to make this conversion in the presence of low serum ionized calcium

92
Q

What two species do not make vitamin D in their skin and rely on it from their diet?

A

cats and dogs

93
Q

What is the metabolism of vitamin D transformation?

A

Vitamin D2/D3 –> liver –> 25 hydroxyvitamin D goes into circulation (what is measured clinically) –> IF NECESSARY, gets directly stimulated by high PTH and low Phosphorus, indirectly by low Ca2+ via PTH and goes to kidney–> renal proximal tubular epithelial cells convert 25 hydroxyvitamin D to 1,25-hydroxyvitamin D (active vitamin D3) via the enzyme D-1-alpha-hydroxylase

94
Q

What cells secrete calcitonin?

A

Thyroidal C cells

95
Q

Fibroblast growth factor 23 is produced by osteocytes in response to what stimuli?

A

hyperphosphatemia or increased vitamin D3. FGF23 is a phosphotonin that lowers serum phosphorus levels by stimulating the kidneys to decrease phosphorus resorption, decreasing D3 production in the renal tubular epithelial cells and by directly decreasing synthesis of PTH in the parathyroid gland.

96
Q

Osteoporosis is a reduction of quality/quantity/both of bone.

A

Quantity. Results from imbalance of bone formation and resorption that is structurally normal but reduced breaking strength.

97
Q

At what reduction in calcium can radiographs detect a change in bone density?

A

35-50% loss

98
Q

Osteoporosis affects which types of bone the most?

A

cancellous bone, especially in the vertebra, flat bones of the skull, ilium, scapula and ribs; metaphysis and epiphysis of long bones

99
Q

What is the function of PPAR-gamma in starvation?

A

Diverts osteoprogenitor cells to become adipocytes instead of osteoblasts, contributes to osteoporosis in starvation

100
Q

Rickets is caused by a deficiency of which substances?
A. calcium
B. phosphorus
C. vitamin D

A

B and C. Calcium deficiency alone does not lead to rickets.

101
Q 
Osteoporosis is induced by all of the following except:
A. copper
B. calcium
C. phosphorus
D. gastric parasitism
E. lead
A

E. lead. A-D can all lead to osteoporosis. Gastric parasitism does this through decreased phosphorus.

102
Q

What is the mechanism of copper deficiency-induced osteoporosis?

A

copper is a component of the enzyme lysyl oxidase which allows the cross linking of collagen and elastin

103
Q

Rickets and osteomalacia are most commonly the result of deficiency in which two nutrients?
A. calcium and phosphorus
B. phosphorus and Vitamin D
C. Vitamin D and calcium

A

b. phosphorus and Vitamin D deficiency are the most common causes of rickets and osteomalacia

104
Q

Susceptibility to vitamin D deficiency is most profound in which species (camelids/sheep/cattle)?

A

camelids, they are normally high altitude animals with thick, pigmented skin to protect against solar irradiation –> movement to lower latitudes predisposes them to Vitamin D deficiency

105
Q

Cutaneous synthesis of previtamin D3 occurs through the activation of what compound?

A

7-dehydroxycholesterol by solar irradiation

106
Q

Calcium deficiency is more likely to lead to:
A. fibrous osteodystrophy and osteoporosis
B. osteoporosis and osteomalacia
C. rickets and osteomalacia
D. fibrous osteodystrophy and rickets

A

A. fibrous osteodystrophy and osteoporosis are the result of hyperparathyroidism leading to excess bone resorption rather than a primary defect of mineralization as in rickets and osteomalacia which occur from a vitamin D or phosphorus deficiency. Calcium deficiency is rarely found by itself.

107
Q 
Rickets may occur secondary to all of the following except:
A. excessive iron intake
B. excessive carotene intake
C. inflammatory bowel disease
D. hypocalcemia
A

D. hypocalcemia. Calcium deficiency leads to osteoporosis and fibrous osteodystrophy, not rickets. Iron and carotenes from lush pasture interfere with phosphorus and Vitamin D metabolism respectively. Inflammatory bowel disease leads to malabsorption of Vitamin D from the GIT.

108
Q 
Hereditary vitamin D-resistant rickets is a common disease in what animal?
A. Hannover pigs
B. Common marmoset
C. Rhesus macaque
D. Cynomolgus macaque
A

b. common marmosets are resistant to 1,25 (OH)2D3 due to a defect in the expression of a vitamin D responsive element binding protein. The Vitamin D3 receptor gene itself is normal.

109
Q

Focal thickening of physeal cartilage with unmineralized osteoid, hemorrhage, infractions and trabecular disruption are features of what bone disease?

a. rickets
b. osteochondrosis
c. fibrous osteodystrophy
d. osteogenesis imperfecta

A

A. Rickets has all four of these features. Physeal cartilage thickening is also a feature of osteochondrosis, but this condition does not have evidence of acute pathology such as hemorrhage or infractions.

110
Q

Persistence of hypertrophic chondrocytes at sites of endochondral ossification both at physes and articular cartilage is a hallmark of what disease?

A

rickets

111
Q

Osteomalacia differs from rickets in two ways which are?

A

Osteomalacia occurs only in mature animals

Growth plates are not involved in osteomalacia

112
Q

Plasma calcium levels in primary hyperparathyroidism are usually (normal/decreased/increased)?

A

increased d/t the affect of the parathyroid adenoma.

113
Q

Plasma calcium levels in secondary hyperparathyroidism are usually (normal/decreased/increased)?

A

normal to slightly decreased

114
Q 
Which of the following compounds produced by tumors can cause hypercalcemia?
A. PTHrP
B. 1,25 (OH)2D3
C. prostaglandins
D. TGF-beta and IL-1-beta
E. All of the above
A

E. all of the above

115
Q

Describe the pathogenesis of renal secondary hyperparathyroidism.

A

Decreased glomerular filtration rate –> reduced clearance of phosphorus –> hyperphosphatemia –> hypocalcemia from inverse relationship of P and Ca–> low Ca stimulates PTH release by parathyroid gland .

Hyperphosphatemia –> osteocytes produce FGF23 –> increased renal excretion of phosphorus but suppression of renal 1-alpha hydroxylase –> decreased Vitamin D3. FGF23 also stimulates 24-hydroxylase to break down 25OHD and Vitamin D3 –> exacerbates hypocalcemia.

116
Q

What is an early stage marker for chronic renal failure in cats that precedes azotemia, is responsible for stimulating increased excretion of phosphorus from the kidney, and causes break down of vitamin D3?

A

FGF23

117
Q 
Nutritional secondary hyperparathyroidism results from:
A. dietary calcium deficiency
B. excessive phosphorus intake
C. vitamin D deficiency
D. all of the above
A

D. Nutritional secondary hyperparathyroidism results from all of the above. vitamin D deficiency alone results in rickets, but when calcium absorption is affected by the deficiency it leads to fibrous osteodystrophy.

118
Q 
Fibrous osteodystrophy in horses is usually the result of:
A. excessive phosphorus intake
B. deficient calcium intake
C. renal failure
D.  grasses deficiency in oxalate
A

A. excessive phosphorus intake. Horses are very sensitive to excessive phosphorus intake which can result in a low Ca:P ratio. Renal failure causes hypercalcemia in horses, not hypocalcemia. Grasses with excessive oxalate can bind calcium and make it unavailable for absorption.

119
Q

Bilateral enlargement of the bones of the skull is a characteristic feature of what bone disease?

A

fibrous osteodystrophy

120
Q

A deficiency of this mineral causes decreased production and increased degradation of cartilage glycosaminoglycans.

A

manganese, associated with periods of drought, can lead to “outbreaks” of chondrodystrophy

121
Q

Congenital spinal stenosis and congenital chondrodystrophy of unknown origin are both associated with a deficiency in what mineral?

A

manganese

122
Q

This mineral is associated with the enzyme lysyl peroxidase and is required for cross-linkage of collagen molecules.

A

copper

123
Q

Growth plates affected by copper deficiency could have differential diagnoses of what two other conditions?

A

rickets and osteochondrosis (except in lambs, copper does not affect the physis in lambs)

124
Q

Secondary copper deficiency can occur from :

a. decreased zinc intake
b. increased molybdenum intake

A

b. increased molybdenum intake as well as increased zinc, iron and cadmium can all cause a secondary copper deficiency. Molybdenum is the big one as a result of thiomolybates productio in the rumen.

125
Q

Vitamin A affects what type of bone the most?

A

membranous bones (skull) –> caudal fossa defect –> cerebellar herniation into the foramen magnum. Also blindness from narrow optic foramina.

126
Q

Teratogenic affects are caused by vitamin A

a. deficiency
b. excess
c. both deficiency and excess

A

c. both deficiency and excess. Swine and large felids are most susceptible

127
Q

Vitamin C deficiency causes reduced secretion or deposition of collagen in addition to what other molecular defect?

A

impaired cross-links due to the lack of deficient hydroxylysine and hydroxyproline

128
Q

Scurvy is the result of a deficiency in what enzyme of the Vitamin C pathway?

A

L-gulonolactone oxidase

129
Q

What species has a congenital defect that can lead to an inherited form of scurvy?

A

pigs

130
Q

The histologic feature of naked spicules of mineralized cartilage within the metaphysis derived from the zone of provisional mineralization in the growth plate is characteristic of what disease?

A

Scurvy, “scorbutic lattice”. Osteoblasts can’t produce osteoid.

131
Q

Fluorine toxicity is best represented by what pathognomonic macroscopic feature?

A

hypomineralization of the outer layer of enamel represented by dry, white, chalky enamel with areas of dark brown to yellow discoloration.

132
Q

Flourine toxicity is characterized by what bony skeletal lesion?

A

periosteal hyperostoses

133
Q

Causes of a sclerotic, radiographically opaque line parallel to the metaphysis can be due to which diseases (multiple species)?

A

lead toxicity, canine distemper virus, bovine viral diarrhea virus

134
Q

Acid-fast intranuclear inclusions in osteoclasts are indicative of what type of toxicity?

A

lead

135
Q 
Vitamin A toxicity is associated with which all of the following except:
A. physeal lesions
B. osteoporosis
C. osteophyte formation
D. subperiosteal hemorrhage
A

D. subperiosteal hemorrhages are associated with molybdenum toxicity as a result of copper antagonism. The physeal lesions of vitamin A toxicity include narrowed growth plates as a result of chondrocyte inhibition. Osteoporosis results from decreased numbers of osteoblasts. The hallmark of Vitamin A toxicity is osteophyte formation (exostoses) but the pathogenesis is unclear.

136
Q 
"Hyena disease" as a result of premature closing of growth plates in the caudal body structures occurs as a result of which type of toxicity?
A. Vitamin A
B. Vitamin B
C. Vitamin C
D. Vitamin D
A

Vitamin A toxicity causes premature closure of growth plates.

137
Q

Deforming cervical spondylosis in cats is the result of which gross feature?

A

extensive exostoses, especially in the cervical spine, from vitamin A toxicity of cats fed beef livers for prolonged periods of time

138
Q

Teratogenic affects are associated with Vitamin A toxicity/deficiency/both.

A

both

139
Q

The toxic component of Cestrium diurnum is :
A. ergocalciferol
B. cholcalciferol
C. 1,25-dihydroxycholecalciferol-glycoside
D. 1,25-(OH)2D3

A

C. The glycoside is the toxic component. Ergocalciferol (or vitamin D2) is the prototypic vitamin D found in plants, while cholecalciferol is the animal form of vitamin D3. D. is what is converted in the kidney to active vitamin D3.

140
Q

Clinical pathology features of hypervitaminosis D include:
A. hypercalcemia with hypophosphatemia
B. hypercalcemia with hyperphosphatemia
C. hypercalcemia with normophosphatemia

A

B. hypercalcemia and hyperphosphatemia both result from Vitamin D toxicity as a result of the increased Ca absorption from the gut, decreased excretion in the kidney, and mobilization of bone.

141
Q 
Histologically, vitamin D toxicity is represented in the bone by:
A. abundant basophilic matrix
B. abundant fibrous matrix
C. normal trabecular patterns
D. abnormal physes
A

A. an abundant basophilic matrix is pathognomonic for vitamin D toxicity in the absence of plasma levels. Physes are normal in vitamin D toxicity but are abnormal in vitamin A toxicity.

142
Q 
The toxic component of Veratrum californicum is:
A. microcystin LR
B. cyclopamine
C. pyrrolizidine alkaloid
D. ergocalciferol
A

B. cyclopamine (because of the cyclopia it causes if ingested on day 14 of gestation).

143
Q 
All of the following are teratogenic effects of Veratrum californicum toxicity in sheep except:
A. craniofacial defects
B. shortening of the distal long bones
C. tracheal stenosis
D. thickened humeri
A

D. thickened humeri is a sign of congenital hyperostosis in piglets. All of the other defects are commonly found in V. californicum ingestion depending on the day of gestation.

144
Q 
Crooked calf disease is the teratogenic effect of ingestion of which plant:
A. Solanum spp.
B. Crotalaria spp. 
C. Cestrum diurnum.
D. Lupinus spp.
A

D. Lupinus spp. (wild lupine) ingestion causes arthrogryposis, limb shortening, torticollis and other twisting teratogenic effects in calves when cows ingest them between 40-80 days of gestation. Solanum and Cestrum dirunum are both plants causing vitamin D toxicity, and Crotalaria spp. are PA toxicity plants.

145
Q 
"Bent leg" syndrome in Australia is associated with ingestion of which plant?
A. Trachymene spp. (parsnips)
B. Senecio spp. (ragworts)
C.  Lantana spp. 
D. Nicotiana pps. (tobacco)
A

A. Trachymene (parsnip) ingestion has been associated with bent leg syndrome in lamb in Australia. Senecio cause PA toxicity, Lantana spp. causes cholestasis leading to icterus and photosensitization in adult cattle (not a teratogen), and nicotiana causes arthrogryposis in piglets.

146
Q 
Which cause of teratogenic limb deformity also causes neurologic disease as a result of an acquired lysosomal storage disease?
A. locoweed 
B. sweet pea
C. wild black cherry
D. castor bean
A

A. locoweed toxicity is best known for its neurologic manifestation as a result of inhibition of alpha-mannosidase which induces a lysosomal storage disease. Sweet pea toxicity inhibits lysyl oxidase which is responsible for collagen cross-linking . Wild black cherry causes arthrogryposis in piglets, and castor bean causes ricin toxicosis which causes GI hemorrhage and liver and kidney necrosis.

147
Q

Equine bone fragility syndrome resulting from osteoporosis occurs secondary to what toxicity?

A

pulmonary silicosis

148
Q

Craniomandibular osteopathy occurs most commonly in which breed?

A

West Highland White Terriers

149
Q

An early finding in cases of hypertrophic osteopathy is
A. decreased blood flow to the distal limb
B. increased blood flow to the distal limb
C. intense lymphoplasmacytic inflammation in the affected limb
D. arteriovenous shunting in the affected limb

A

B. increased blood flow to the affected limb is always an early sign of HO. Mild inflammation is common, and an arteriovenous shunt in the primary thoracic mass has been proposed but not proven to account for some of the pathogenesis of HO.

150
Q 
Exostoses in dogs are potential sequelae in all of the following cases except:
A. Vitamin D toxicity
B. Hepatozoon americanum infection
C. Pulmonary osteosarcoma
D. Vitamin A toxicity
A

A. Vitamin D toxicity does not commonly cause exostoses.

151
Q

The layer of granulation tissue surrounding a sequestrum is:

A

an involucrum

152
Q

What is the pathogenesis of Legg-Calve-Perthes disease?

A

ischemia from vessels being occluded as they leave the femoral head through narrowed intraossesous canals –> intracapsular tamponade –> increased intra-articular pressure –> infarction combined with weigh-bearing –> fracture and collapse of the necrotic trabecular bone –> flattening of the femoral head –> degenerative arthropathy. Can also cause physeal disruption

153
Q 
Causes of osteomyelitis include all of the following except:
A. Halicephalobus gingivalis
B. Leishmania
C. Hepatozoon americanum
D. Staphylococcus aureus
E. Salmonella
A

C. Hepatozoon americanum causes a proliferative exostosis that is not inflammatory. S. aureus invades osteoblasts.

154
Q

Pro-inflammatory cytokines induce bone (resorption/deposition).

A

Resorption through activation, differentiation of osteoclasts. They are produced by osteoblasts.

155
Q 
Brodie's abscess refers to a:
A. sequestrum
B. involucrum
C. abscess in the metaphysis or epiphysis separated by woven bone and fibrous tissue
D. subperiosteal abscess
A

C. abscess walled off from the rest of the metaphysis or epiphysis.

156
Q

The most common presentation of Coccidioides in dogs is?

A

osteomyelitis

157
Q

The most common presentation of Blastomyces is?

A

pneumonia, dogs serve as sentinels for infection

158
Q

Growth retardation lattices are classically associated with infection of which viruses?

A

BVDV, CSF, Border disease virus, Canine distemper

159
Q

Hypertrophic osteodystrophy has which two classic features not related to periosteal proliferation?

A

metaphyseal necrosis and inflammation

160
Q

Infraction lines in the metaphysis are a common feature of what idiopathic condition in young dogs?

A

Hypertrophic osteodystrophy (AKA metaphyseal osteopathy)

161
Q

The histologic lesions of metaphyseal osteopathy include all of the following except:
A. normal physes
B. lack of osteoid deposition on trabeculae
C. suppurative inflammation
D. normal numbers of osteoblasts

A

D. osteoblasts are absent in MO, hence the lack of osteoid deposition.

162
Q

The histologic feature of canine panosteitis is:
A. fibrovascular tissue in the marrow of long bones
B. suppurative inflammation in the marrow of long bones
C. unmineralized bony trabeculae

A

A. fibrovascular tissue in the marrow of long bones contributes to the radiopacity of panosteitis, which does not have associated inflammation (misnomer)

163
Q 
Ossifying fibromas occur most commonly in:
A. Young horses
B. Old horses
C. The mandibles of sheep
D. The maxilla in cattle
A

A. Young horses < 1 year of age. The occur most commonly on the rostral mandible.

164
Q

Osteoblasts in osteosarcoma will be positive for what enzyme?

A

alkaline phosphatase

165
Q

What is expressed by osteoblasts that causes osteoclasts to differentiate?

A

RANKL

166
Q

A useful clinical pathology prognostic factor in osteosarcoma is?

A

bone-specific alkaline phosphatase

167
Q

Periosteal hemangiosarcoma arises from what layer of the periosteum?

A

cambrium layer

168
Q

Parosteal hemangiosarcoma arises from what layer of the periosteum?

A

outer fibrous layer

169
Q

Osteochondromas differ from osteochondromatosis in that:

A

the marrow cavity of osteochondromas is continuous with the primary bone affected, where in osteochondromatosis the cavity is not continuous.

170
Q

Multilobular tumor of bone occurs most commonly in what species and anatomic site?

A

the skull of dogs

171
Q

Multiple circular, oval, or irregularly-shaped nodules of cartilaginous, osseous, or osteocartilaginous tissue separated by narrow fibrous septa are a characteristic feature of what condition?

A

multilobular tumor of bone

172
Q 
Unlike osteosarcoma, chondrosarcomas:
A. contain bone
B. contain osteoid
C. can cross the joint space
D. are more common in the long bones
A

C. can cross the joint space. Chondrosarcomas can contain bone as a result of endochondral ossification not production of bone (or osteoid) from malignant cells. Chondrosarcomas are more common in the flat bones.

173
Q

A determination of malignancy for a chondrosarcoma is most dependent on:
A. presence of necrosis
B. presence of endochondral ossification
C. presence of a single mitotic figure
D. presence of a fibrillar chondroid matrix

A

C. presence of a single mitotic figure indicates malignancy. The other three are commonly found in chondrosarcomas.

174
Q

Plasma cell myeloma can be associated with all of the following except:
A. M-component fragment of immunoglobulin on elctrophoresis
B. Bence-Jones proteinuria
C. hypocalcemia
D. hypercalcemia

A

C. hypocalcemia is not caused by plasma cell myeloma

175
Q

The difference between a benign bone cyst and a aneurysmal bone cyst is:

A

The benign bone cyst is unicameral and the aneurysmal bone cyst is multiloculated.

176
Q

The cysts of intraosseous epidermoid cysts are lined by:

A

stratified squamous keratinizing epithelium

177
Q

The relative lack of IVDD between the second and tenth disc spaces occurs because of the:
A. dorsal longitudinal ligament
B. ventral longitudinal ligament
C. conjugal ligament

A

C. The conjugal ligaments extend from the ribs and provide extra support for the dorsal longitudinal ligament in this area.

178
Q

Spondylosis is most common in what species?

A

Aging bulls

179
Q 
Suppurative arthritis composed of viable, nondegenerate neutrophils is common in what conditions:
A. Borreliosis
B. Mycoplasmosis
C. Immune-mediated arthritis
D.  All of the above
A

D. all of the above have nondegenerate neutrophils in synovial fluid preparations

180
Q

Chronic erysipelas commonly presents as what lesion?

A

arthritis and diskospondylitis

181
Q

Fibrinopurulent polyarthritis and osteomyelitis is a feature of what bacteria in sheep after tail-docking and castration?

A

mostly Erysipelas (also Streptococcus, Staph hyicus and Haemophilus parasuis (i.e. Glasser’s disease))

182
Q

The most common cause of arthritis in dogs is:

A

Staphylococcus aureus

183
Q

Histophilus somni in sheep presents with what gross lesions?

A

multifocal, linear hemorrhages throughout the carcass but best in the muscle. No pneumonia.

184
Q

Lyme disease presents with what three lesions in dogs?

A

arthritis, myocarditis, nephritis

185
Q

What tick species transmit Lyme disease?

A

Ixodes scapularis and Ixodes pacificus

186
Q

What species of Chlamydia causes arthritis?

A

C. pecorum

187
Q

What are the 3 Mycoplasmas of swine and their lesions:

A

Mycoplasma hyopneumoniae: enzootic pneumonia
M. hyorhinis: polyserositis and polyarthritis in pigs < 10 weeks
M. hyosynoviae: polyarthritis WITHOUT POLYSEROSITIS in pigs > 10 weeks

188
Q

Mycoplasma bovis commonly presents as:

A

arthritis, mastitis, pneumonia

189
Q

Polyarthritis in an aborted late-gestation bovine fetuses is associated with:

A

Ureaplasma diversum

190
Q

A common clinical feature of CAEV is:

A

unilateral or bilateral carpal hygromas

191
Q

A cause of protozoal arthritis in dogs is:

A

Leishmania donovani or Leishmania infantum

192
Q

Fistulous withers is associated with inflammation of the:
A. cranial nuchal bursa
B. caudal nuchal bursa
C. supraspinous bursa

A

C. supraspinous bursa. The cranial and caudal bursas are associated with the term “poll evil”.

193
Q 
Fistulous withers and poll evil are associated with what pathogens:
A. Brucella abortus
B. Actinomyces bovis
C. Staphylococcus
D. Streptococcus
E. All of the above
A

E. All of the above

194
Q

What species of Aspergillus is associated with diskospondylitis in dogs?

A

A. terreus

195
Q

Pseudogout is associated with the deposition of what?

A

calcium pyrophosphate dihydrate crystals

196
Q

Gout does not occur in mammals except humans because of the enzyme:

A

uricase

197
Q

What is the pathogenesis of Chinese SharPei syndrome?

A

duplication of the gene upstream from hyaluronic acid synthase 2, which leads to increased production of hyaluronic acid by dermal fibroblasts –> immune trigger–> cyclic fever and pain –> periarticular cellulitis +/- arthritis

ACVP Phase II Exam - Anatomic Pathology (25 decks)

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