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9.27.97
PBL session

some people described parathyroids as "nodular"
maybe before you saw a gross picture of thyroids and parathyroids, you 
got confused b/w thyroid and parathyroids. the parathyroids were 
enlarged, not nodular. they are ovaloid/discoid and they sit on top of 
the thyroids, and are diffusely, smoothly enlarged. 

one major thing that was a final question - w hat are the "usual" causes 
of the syndrome in dog and horse...about half the groups got it correct. 
books do mention that dietary causes can be associated with it in dogs, 
but that isn't a "usual" cause. the usual cause is chronic renal failure. 
the kidney experiences reduced GFR, leading to retention of phosphorus 
and excretion of calcium. PTH senses low serum calcium, and the cycle 
begins. most commonly we see this in young dogs with renal dysplasia 
which makes sense b/c bones are very labile and metabolically active. why 
are mandible/maxilla/thighbones predisposed? those bones are USEd more 
often, are more active, and therefore are more metabolically active as 
well. physical stress increases bone metabolism and these more active 
bones are preferentially affected. 

in a few of the answers there was some...everyone knows osteoclasts do 
the resorbing of bone, but there was some confusion. 
as discussed Friday (when I was not here), osteoblasts are on the edge of 
bone, and have PTH receptors. they are activated to release interleukins 
IL 6 and IL 11 which activate osteoclasts. so PTH activates osteoblasts 
which release ILs which activate osteoclasts. there is also a 
morphological change of the osteoblasts once they are activated - they 
get rounded, hypertrophied, and they pull apart from one another leaving 
little gaps. "rolling" phenomenon of o-blasts moving along osteoid, 
leaving room for osteoclasts to get between them and enter bone. o-blasts 
may also be releasing other factors to attract o-clasts.

prizes are being given to group 10, 14, 11, 8, and 9. yay! I am in group 
10.
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dr mcmanus on bone (cont)
1:30-2:30

pluripotent stroma (mesenchyme)--> osteoblasts -->osteocytes and "surface 
osteocytes" aka osteoblasts. the osteocytes are long lived cells lasting 
20-30 yrs. the osteoblasts have the PTH receptors and are active in 
calcium homeostasis. when activated they are rounded and have gaps 
between them to allow passage of osteoclasts

granulocytic macrophage line (GM-CFU)-->monocyte line-->osteoclasts
osteoclasts eat/resorb bone. they are the pacman of bone and are 
multinucleated. 

slide: dog with small, pitted, irregular kidneys. frequent urination, 
isothenuria (not concentrating urine). this dog had fibrous 
osteodystrophy secondary to chronic renal failure. this slide is of nasal 
septum, turbinates, and maxiilla. a tooth is visible but buried in 
massive fibroplasia of maxilla. the thickening/fibroplastic/loose 
appearance is visible in septum and turbinates as well. this dog grossly 
had a big head. 

slide: histo section from rat with fibrous osteodystrophy. we see a bony 
spicule with osteoid outside of it. (remember that slides are often 
demineralized. large multinucleated cells with brush border: osteoclasts. 
spaces they are in when actively resorbing are "something lacunae" - 
hauslip's lacunae? 

slide: fibroplasia - fibrous CT filling in bone. increased numbers of 
osteoclasts. 

FRACTURES: two broad categories of them

1. most common. TRAUMATIC fracture - secondary to trauma, obviously. dog 
hit by car or whatever. bone is normal, but has been hit with sudden 
force/impact. bone not good at sudden forces - better at chronic weight 
bearing.

2. less common. PATHOLOGIC fractures which occur in abnormal diseased 
bones. rickets, osteomalacia - soft bone, often see compression 
fractures. or think of osteoporosis - hip, elbow fx that occur from 
forces which wouldn't cause fracture in normal bone.

very simple terms:

simple or closed fractures do not break the skin. the skin is intact and 
is a barrier to infection.

open or compound fracture: complete disruption of skin and soft tissue - 
bone protruding through skin

transverse fractures - go across the midline (perpendicular to 
longitudinal axis)

spiral fractures- curve around the bone - need two views to see well. 
seen with torque force, twisting force - dog jumping out of tub, horse 
stepping in hole

greenstick fractures - common in young animals, bones dynamic and soft, 
start a transverse fracture and then a bending of bone - bone will bend 
on the side opposite the fracture. fracture doesn't go all the way 
across. 

physeal fracture - along the growth plate, which is cartilage. what 
happens if you see a physeal fracture? cessation of growth if not 
repaired or if it doesn't heal well. if it heals ok the bone will still 
grow. 

stages of healing of fractures.
we try to put things into a timeframe for learning purposes, but these 
things, many of them, are cascades that occur somewhat simultaneously, so 
our divisions are somewhat artificial - snapshots in time.

SIMPLE TRANSVERSE FRACTURE - CLOSED, MINIMAL DISPLACEMENT, NO INFECTION:

what happens at fracture site? there has been direct blunt trauma. the 
cells at the edges of the fracture are going to die. the periosteum 
(saran wrap around bone) containing blood vessels and fibrous CT will 
bleed/hemorrhage. direct trauma and ischemia secondary to disruption of 
blood vessels is what causes necrosis of bony edges. clotting cascade 
starts in periosteum. we've also disrupted the marrow cavity - sinusoids 
and possibly nutrient arteries -> so we see an organizing hematoma in the 
marrow cavity. granulation tissue will start forming. angiogenesis is 
occuring, and fibroplasia is occuring big time (granulation tissue is 
made of blood vessels and fibrous CT). macrophages will start coming in 
to remove necrotic bone, inflammation to remove the debris. so we start 
seeing organization of granulation tissue and formation of fibrous 
callous. once the fibrous CT bridges the gap externally and internally, 
that's a "bridging callous" and is important to note during radiological 
evaluation.
then, the fibrous CT still needs to be replaced with bone. osteoblasts 
and osteoid still needed. so ideally, we will get intramembranous bone 
formation. this means you get the appropriate nutrients, cytokines, 
oxygen, and you get direct activation of mesenchymal cells to become 
osteoblasts, lay down osteoid, become osteocytes. if conditions aren't 
ideal, you may get endochondrial ossification using cartilage 
intermediate. now it needs to be remodelled and shaped. we remove the 
bone from medullary cavity - it's resorbed. normal blood flow is 
restored. bone grows in cortical region. the callous on the outside of 
the bone gets smaller and smaller until it's a tiny imperceptible bump. 
in young animal 6-8 wks for good callous formation. in older animals, it 
can take longer. 

suboptimal healing conditions hamper fracture repair. eg, poor 
stabilization - mobile fracture ends move around and fail to align 
properly, and cause repeated damage to local tissues. more hemorrhage, 
etc. blood flow is further disrupted. 

what are some iatrogenic problems with bone repair? 
steroids? shouldn't inhibit healing if used properly.
splinting? yes, external fixation if done improperly can impair bone 
healing.
pins? what if you use a pin that is too small? you don't stabilize 
fracture well enough - can still get mobilization. or could shear 
nutrient artery accidentally. too large of a pin can cause another 
fracture, or can cause more hemorrhage, vascular disruption, or even 
pressure necrosis of surrounding bone. 
what are limitations of external fixation? what if you have a fat 
rottweiler with no brain? you have a lot of stress and weight on the 
fracture. dog won't leave it alone. not all animals tolerate external 
fixation. obese animals may need internal fixation. older animals have 
slower repair of tissues. 

in handout there are two summaries of this along with temporal sequence 
of what goes on. 

think of a COMPOUND FRACTURE: dog hit by car, rolled, dragged. gravel etc 
in wounds. major concerns - bacterial infection! what cell gets involved? 
neutrophils. neutrophils release enzymes, oxygen radicals, inflammatory 
mediators, etc. this causes tissue damage and necrosis as well. this 
needs to be debrided - this delays healing because all the debris must be 
removed before it can heal. 

sequelae to fractures:

inflammation of bone
osteomyelitis
iatrogenic infection secondary to internal fixation
healing with normal bone structure is best response
two worst outcomes: nonunion or malunion

dog with leg caught in leghold trap - lower limb can form "pseudojoint" - 
two bony callouses - nonunion.

or, ends can join together at a funny angle, twisting to one side, joined 
by a callous, and edges of fractures are not aligned. you can surgically 
break these and realign them. (malunion)

inflammation processes in bone:

same pathways as other inflammation. all same vascular changes and 
cellular infiltrates. remember: must have blood supply for inflammation 
to occur. 

osteitis: inflammation of BONE tissue itself. remember canaliculi - 
that's where inflammation is centered. it's difficult because of numerous 
vascular envelopes to keep inflammation isolated here

osteomylitis: inflammation of bone and marrow

periosteitis: inflammation of periosteum - spreads

spondylitis: inflammation of vertebral body

routes of infection: soft tissue contamination spreading to underlying 
structure eg gingival/periodontal-->maxilla, mandible

local extension of direct contamination of fractures

hematogenous route - food animals, horses, large ungulates: primary route 
is hematogenous secondary to naval ill or umbilical infxn

vessels looping under growth plate -> bacterial lodge in metaphyses, and 
can spread into epiphysis via blood. in general in most other species 
physeal plate is avascular barrier to infection

sometimes endothelial damage/hypoxia/thrombosis -->ischemic necrosis.

tx: antibotics sometimes clears infxn allowing healing
but bone abscesses common, abx don't get into bones well. can have lytic 
necrosis and much tissue destruction. inflammatory mediators stimulate 
bone formation. often this can occur out in periosteum. bone with 
osteomyelitis may develop elevation of periosteum with new bone formation 
under it, in response to inflammation. sometimes may see triangles of new 
bone "codman's triangle" = new bone formation in periosteum. 

also with inflammation we see vascular damage, necrosis. may get 
sequestrum formation - island of necrotic bone covered by fibrous CT - 
needs to be curetted out. or can have chronic active inflammation - 
continuous bone destruction and periosteal bone formation. enough damage 
can predispose for pathologic fractures secondary to normal wear and tear 
or increased susceptibility to trauma related fractures

types of inflammation:

suppurative: bacteria, esp pyogenic bacteria. neutrophils, pus. 
(most common types of bacteria listed in handout, don't have to know)
bone very porous, inflammation in medullary cavity, stimulating 
osteoclasts and osteoblasts, can see pathologic fx and sequestra. histo - 
infl infiltrate, abcess formation, etc. 

bacterial diseases: probably most common one is "lumpy jaw" or 
actinomycosis. in developing countries eg puerto rico with oxen this is 
significant problem. damaged gingiva, local infection, spreads to jaw 
bone. also seen in oxen around here. actinomyces bovis is gram + 
filamentous bacteria, hard to tx and eliminate. infxn is result of 
invasion of traumatized gums from rough forage..drains into 
lymphatics...into bone. swollen jaw, draining fistulous tracts, sulfur 
white granular material loaded with bacteria.

also common esp in sheep is foot rot: soft hooves (esp white faced sheep) 
resulting in inflammation of p3, wt loss, animals don't want to graze - 
will kneel b/c feet hurt. "dichelobacter nodusus" there is a vaccine for 
sheep against this. also preventive foot care

bull nose of swine - seen when needle teeth clipped - anaerobic fusiform 
bacterium.

slides:

horse came in for colic sx. they removed a pedunculated lipoma. horse 
kicked wall in recovery and got comminuted fx just above hoofline. was 
this pathologic fx or strictly traumatic? was strictly traumatic.

slide: cranial vault with puncture wound right through center. two male 
horned goats. one gored the other in the head and a local abscess 
developed. no clinical neuro signs were present! weird. would expect 
eventual meningitis.

slide: vertebral column. one of the vertebrae looks "smooshed" eg it 
isn't as wide as the others from front to back, and has an area of 
pallor. this vertebral body was fractured. a callous formed and put 
pressure on the spinal cord. sections of cord show hemorrhage. 

sequela to ischemia (most common cause of bony necrosis) - see necrotic 
bone - lacunae are empty, and bone is being laid down on the outside of 
the necrotic tissue. large pieces of necrotic bone must be removed to 
facilitate healing.

synovium thick, red, w/fibrin clots. physis of this foal has blood 
vessels crossing. area of metaphyseal inflammation has spread from 
metaphysis to epiphysis. 

infection - pus, exudate - totally replacing growth plate. removing 
exudate shows no growth plate left. often see pathologic fractures across 
the physis that isn't there anymore. abscesses also occur. when these 
occur in vertebrae there is compression of the cord

histology: degenerated neutrophils, exudate.
histo: physeal abscess - large area of lytic necrosis filled with 
neutrophils

jaw - buccal surface - training tracts with white/yellow sulfur granules. 
with soft tissue removed we see huge holes in jawbone that were formerly 
filled with pus and sulfur granules (lumpy jaw). the sulfur clumps are 
protein deposits surrounding bacteria.

foot rot; grossly smells bad, dark, soft. osteolysis of p3, separation 
from overlying hoof wall.

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note: in the handout there is a typo under "compact bone". cross out the 
part that says "lamellar/mature" in parentheses. just cross them out. 
shouldn't be there. 

another thing from the beginning is that there were some references used 
to make the notes - Thompson's special veterinary pathology, something 
you may want to look at, and for histology you might want to look at 
Bank's Applied Veterinary Histology, and finally for small animal people, 
check out the JAVMA hip displasia symposium from last year. 

back to inflammation. 

GRANULOMATOUS: just like other systems - think of mycobacterium, mycotic 
agents. grossly similar to suppurative osteomyelitis but exudate is 
firmer, more caseous. can see pathologic fx, periosteal bone formation. 
hallmark of this type of inflammation is *giant cells* and *macrophages*
this is most commonly seen due to aspergillosis of nasal cavity of dog 
(some breeds more prone to this). pet birds also get this. macaws, 
budgies. variety of agents listed in handouts with unique presentations 
and appearances. large military population that moves around a lot 
requires that you know about many geographically diverse agents.

slides:

radiograph of a bone with large radiolucent areas of bone destruction, 
some areas of new bone formation. ddx - inflammation or neoplasia. can be 
hard to tell apart. both show necrosis of bone, inflammation, etc. this 
is granulomatous osteomylitis

gross specimen. frontal sinuses of dog full of thick, nodular 
inflammatory tissue due to aspergillosis. presentation - rhinitis, nasal 
exudate prurulent, hemorrhagic.

coccidioidomycosis: mexico, arizona, utah, socal, etc. lower digits show 
lysis and loss of bone in phalanges. some fuzzy new bone seen growing in 
periosteum. this bone is OUTSIDE the cortex, seen as wedge shaped 
outgrowth of cortex. caused by inflammatory mediators. 

histo - many macrophages and distinct, large endospores.

blastomycosis: endemic in midwest. big problem. commonly seen in hunting 
dogs - common presentation - dog is "ADR" and some exudate/draining on 
paw. slight dyspnea. lungs at necropsy are not normal salmon pink - are 
deep red, roughened pumice stone appearance, little yellow nodules, lungs 
are stiff, don't collapse normally. severe granulomatous pneumonia. 

histo of bone: severe granulomatous inflammation with distinct organisms 
involved in broad base budding. can also see in transtracheal wash or 
skin scraping or skin biopsy

histoplasmosis: mississippi river valley area. these organisms are seen 
inside macrophages. tiny, pinpoint. hard to see. typical granulomatous 
rxn is seen with this organism.

cryptococcus: huge unstained slime capsule area full fo small organisms. 
seen in cats with sinusitis/meningitis. sinuses filled with clear 
jellylike stuff - these organisms. 

bone sectioned: can see distinct granulomas, some new bone growth on 
surface.

most often inflammation/infection is suppurative. the mycotic infxns are 
fairly rare but are seen in some regions. the other agents eg viruses are 
very very uncommon, but may be seen, rarely. most common route of viral 
infxn is hematogenous spread. that usually means you end up getting a 
vasculitis from the infection. then you get thrombosis and ischemia nad 
actual osteonecrosis. distinct dzs reported from viruses: osteosclerosis 
secondary to avian osteopetrosis (avian leukosis virus) which stimulates 
osteoblasts. also something about canine distemper (see handout). 

there's a broad category of idiopathic inflammatory diseases with 
distinct appearances. much isn't known about them but we should be 
familiar with them but not know for exam per se. focus on signalment and 
rads

k9 hypertrophic osteodystrophy mostly in young pups of lg breed dogs. 
febrile, painful, lame. bony proliferation palpable in metaphyseal 
region. lysis just above physeal plates. histo: inflammatory changes. 
possibly viral origin. neuts, plasma cells, lymphocytes, activated 
osteoclasts. distinct band of necrosis and hemorrhage above physeal plate 
- visible on radiographs. 

a bit more common, in GSD: eosinophilic panosteitis or k9 panosteitis. 
peripheral eosinophilia often seen in these pts. medium to lg breed dogs, 
esp GSD. 2 mos to 5 yrs, mostly first year of life. mostly males 
affected. present with shifting leg lameness, can have repeat episodes, 
cycle leg-leg. minimal radiographic changes seen during acute episodes. 
lesions seen a couple of weeks later - new bone formation seen in 
medullary cavity of diaphysis over entry of nutrient artery. histo: new 
bone and fibroplasia. not much inflammation. 

craniomandibular osteopathy: terriers mostly, also labs. young animals. 
dogs come in with large, swollen heads. periosteal new bone formation 
over tympanic bullae, mandible, cranial vault. new bone on histo, also 
periosteal and subq fibrosis and inflammation. genetic predisposition and 
possibly infectious etiology. also similar thing in bullmastiffs

HPO hypertrophic osteopathy - see handout for exact correct name - 
distinct new bone formation on distal limbs, mild histologic swelling, 
infl, in subq tissues. bone over phalanges is forming. 

necrosis of bone almost always due to vascular injury, probably number 
one cause is fracture. might see hypoxia/anoxia with inflammation if 
there's enough vascular damage. also an idiopathic syndrome of bilateral 
femoral head necrosis which is seen in humans esp small children - 
complete necrosis of femoral heads. also seen in dogs - in small breeds 
just remove fem head. grossly see deformed, flat, crumbled femoral head. 
no osteocytes seen on histo

slides:

hypertrophic osteodystrophy - age 3-6 mos, lameness, febrile, don't wanna 
move, albuminuria, elevated WBC. legs are swollen, bumpy, irregular, firm 
bony projections over metaphyses. 

rads: physis present, and under that is increased opacity -->bony 
necrosis - and a lytic band behind. also new bone seen out in metaphysis. 
necrosis right above physeal plate.

eosinophilic panosteitis: young animals up to 5 yrs of age. shifting leg 
lameness. pain in diaphysis. rads show increased density/opacity in 
medullary cavity centered over nutrient artery entrance. 

craniomandibular osteopathy: 4-8 mos age onset, often present with 
dysphagia, large head, fevers. rads: increased white, fuzzy areas of new 
bone formation. roughened, feathery appearnace, no sharp edges. grossly 
there are fuzzy bony projections all over the jawbones, bullae, 
basisphenoid and other bones in head.
histo: fibroplasia in subcutis, band of inflammation at periosteum

slide: fuzzy proliferations of bone - hypertrophic osteopathy in dog with 
primary cardiac lesion. distinct perpendicular bony growths outside the 
cortex of the bone. 

--
rads: flattened, irregular femoral head, areas of decreased density 
-->necrosis. dye used to detect vascularity shows avascular areas, bone 
loss.

histo: eosinophilic areas without osteocytes. 
empty lacunae
--

end of idiopathic conditions (see handout)

abnormalities of development:

can see abnormal cartilage and bone growth from primary genetic defect, 
multifactorial situation (probably most common  - genetic predisposition 
with many contributing factors to development of clinical dz), some few 
toxins (rare). faulty nutrition can also cause problems.

can see generalized systemic effects or local effects eg scoliosis, flat 
chest, etc. 

see handout for examples.
ones in small print not important

common example of pleotropic effect: chondrodysplasia of alaskan 
malamutes: one genetic defect causes multiple problems: testiculopathy, 
hemolytic anemia, etc from lysyl hydroxylase defic

osteopetrosis: defective osteoclastic function: marble bone disease

tibial dyschondroplasia in broiler flocks - multifactorial problem, 
strong genetic predisposition, influenced by diet, fat content, handling, 
etc. cause of major economic losses w/affected birds needing to be 
destroyed

spider lamb dz. genetic problem. breeders resisting this. first reported 
in suffolks, now in hamps, breeders won't admit it...these animals are 
thin, tall, gangly. roman nose often occurs. essentially this is retained 
cartilaginous cores in bone. may look normal at birth or be abnormal at 
birth. even twins may look different at birth. 

chondrodystrophy breeds - basset hounds are normal for themselves but 
have abnormal bone development

OCD osteochondrosis: variety of toxins involved - veratrum californicum 
at certain time if eaten by pregnant ewe causes specific lesions

contracted foals in horses - many theories, some think fetal 
malpositioning, some think toxin, some concern exists re: abnormal muscle 
development. 

another idiopathic dz - crooked calf with crumpled/folded legs.

slide: farmer brought calf to NBC, had never walked since birth. 
vertebral column is very bizarre looking. areas of missing vertebrae and 
area of missing cord in this perfect midsaggital section. there are 
abnormal vertebral bodies. there has been agenesis of cord. this was a 
neural tube defect - localized developmental defect.

wildebeest calf born dead - dystocia. nasal septum deviated "wry nose" 
and also cleft lip - harelip - and cleft palate. this animal had multiple 
orthopedic abnormalities. 

slide: tibia of normal 4 wk old broiler. uniform physis. slide of 
affected age matched bird: cartilage core had been retained - tibial 
dyschondroplasia. cartilage didn't form normal growth plate or bone. it 
is prehypertrophied cartilage not arranged in nice columns. 

slide: lamb with spider lamb dz - roman nose, multiple retained 
cartilaginous cores through vertebral column, carpi. angular limb 
deformities, bowed bones. displacement of tendons occurs due to abnormal 
shape of limbs.

some of our chondodystrophies in poodles, mini dogs have been selected 
for.

the leg bones of great danes compared to mini poodles make our selection 
for particular genes very evident. 

slide: basset hound: mushroom appearance/short bones/chondrodystrophy
slide: crooked calf: seen in canada, western US. possible blue pine 
toxicosis. 
soft joints, walks on carpi, developmental defect of bone. 


neoplasia: most important one is OSTEOSARCOMA. 
slide: osteoma. well circumscribed expansile mass of fairly normal 
looking bone. these are rare not seen often but can occur
slide: osteosarcoma. breed/age predilection data gathered here. hotspots: 
proximal humerus and distal radius. those are main sites where this 
occurs. age predilection: peak in middle aged dogs 4-7 yrs - highest 
incidence in giant breeds followed by large and medium breeds. these 
tumors are destructive of bone, can produce bone, can also contain 
cartilage and fibrous ct. main thing is they produce osteoid and bone. 
destruction of normal cortex, cavitation, necrosis, hemorrhage. mets 
early often via blood to lung. if palpating would feel firm, poss gritty. 
on rads would see increased hard bone density, maybe motheaten look.can 
see elevation of periosteum and new bone growth nearby. can be tough to 
biopsy - avoid areas of new bone formation, get into center of neoplastic 
mass. if you have lots of swollen soft tissue, make sure you use long 
enough needle!
histo: mass erodes through cortex. densely cellular proliferation. small 
oval cells producing bone. 







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