Five-month-old Hereford-crossbred steer
(Bos taurus).Calves fed
potatoes, 1 death in the herd. Calf showed neurological signs, focal seizures,
blindness, head pressing. No response to thiamine or florfenicol.
brain gyri were swollen and flattened. The rumen pH was 8, and the rumen contained
two, small balls of plastic bags. The jejunum had several Monezia expansa cestodes.
The costochondral junctions had a 7mm-thick, dense line of presumed cartilage
core retention. Radiographs of thin sections have a dense white line.
section of decalcified rib costochondral junction is examined. The zone of
proliferating chondrocytes is longer than expected and proliferating
chondrocytes can be seen in trabeculae far into the rib in retained, calcified
cartilage. The invasion into chondrocytes is uneven, and while osteoblasts
pile up in the hollow profiles of early-calcified chondrocytes, osteoclasts do
not extend into these chondrocytes. The chambers of the initially invaded
chondrocytes have erythrocytes, and a punctate, <2um basophilic dusting
often fills these early chambers. The provisional calcified cartilage is
retained far into the rib marrow space with only thin, apposed osteoid/bone.
The provisional bone is thick and retained. Some osteoclasts are free in the
marrow as opposed to being apposed to surfaces. Osteoclasts show more ani-socytosis
with both size and shape variation and variable numbers of nuclei (osteoclastic
dysplasia). Many dysplastic osteocytes have large, round and multiple
inclusions. Bone marrow is otherwise hypocellular with serous degeneration of
fat, and normal marrow constituents of the rib appear more distal from the
costochondral junction than in a normal physis.
Rib, physis: chondrodystrophy with osteo-sclerosis,
retained calcified cartilage; osteoclast dysplasia/hyperplasia.
Blood lead concentration: 0.7 ppm (normal <0.3 ppm) Kidney lead
concentration: 6.2ppm (Normal: 0.1-1.0 ppm) Hematocrit: 31%.
Lead toxicosis, physeal dysplasia
line examination is part of a routine diagnostic necropsy examination. It
demonstrates nutritional imbalances in any production mammal, or as in this
case, mineralized cartilage retention usually due to osteoclast problems such
as with BVDv persistently infected calves, canine distemper (Thompson 2007),
and in our case, lead poisoning. Unfortunately, many people do not do it
The bone lesions of lead poisoning were well described in the early 1930s by several authors studying poisoned children, and those descriptions remain valid. (Reviewed by Park 1933). The lead line in children will form once blood lead is 70-80 ug/dl. One month after treatment with chelating agents, the line separates from the zone of proliferating chondrocytes, and it will disappear in 4 years (Sachs 1981). Later descriptions added electron microscopic findings indicating that osteoclasts often lost their ruffled border and were less intimate with the surfaces (Eisenstein 1975). Nuclear and cytoplasmic inclusions were seen with EM. The cytoplasmic inclusions increased in size in osteoclasts more distant from the physis (inclusions fused?). Ultimately, morphologists concluded there is an inability for chondroclasts/osteoclasts to remove metaphyseal calcified cartilage cores presumably because they cannot degrade (or excrete) it. They are thus constipated.(Eisenstein 1975) Interestingly, lead binds to osteocalcin to make a more compact molecule, and lead can cause a 40% increase of hydroxyapatite mineral over that bound with calcium (Dowd 2008). Might such modifications lead to indigestion- to continue the ANALogy (JFE)? The increase in osteoclasts is a compensatory hyperplasia. Lead poisoning-induced, osteoclast intra-nuclear inclusions are visible with electron microscopy (Hsu 1973). These inclusions of lead and protein aggregates are best-known in proximal renal tubules (where they make up 90% of the lead in kidneys), but are also in osteoclasts and less frequently in hepatocytes and glia (Goyer 1970, Moore 1974). Experimental and spontaneous studies demonstrate they may appear and regress in intoxicated individuals (Hzu 1973, Hamir 1983, Goyer 1970). EM shows them more frequently, and they are seen occasionally in light microscopy using Ziehl-Neelsen acid-fast stain. We could not see them reliably with acid-fast or PAS staining. In experimental lead poisoning of dogs (Zook 1972), metaphyseal sclerosis with retention of cartilage trabeculae having more mineralized cartilage with increased numbers of large osteoclasts distal from the physis were seen.
Obviously, the lines are seen in young animals forming bones. Lead intoxication is more common in calves and thus are seen during calving season. Cattle usually have exposure to old lead base paints, discarded lead batteries, solder, linoleum, mining, smelting, and crankcase oil (ingested or used on skin as an insect repellant!) in pens or pastures (Blakley 1984, Burren 2010). Sometimes, recycling materials are incriminated (Payne 2008). Cases where pastures are previous shooting ranges have produced lead intoxications (Payne 2013). The decreased use of leaded gasolines has reduced risk of lead poisoning (Burren 2010). Blood, liver and kidney are favored samples to measure lead. When examining blood, many animals having measurable blood lead will not show signs (diarrhea, seizures, bruxism, blindness, hemorrhages). The half-life of lead in exposed cattle is 135 days, std deviation 125 days (Bischoff 2012, Voigt 2010). Our calf was ill and had laminar cortical necrosis. Unfortunately, a specific lead source in this case was not found, and a farm visit was not allowed. The potatoes mentioned in the history were never provided and are considered a red herring.
bone: Physeal dysplasia, with retention of cartilage cores, and focal necrosis, Hereford-crossbred steer, Bos taurus.
We thank the contributor for his thorough and often satirical
review of the skeletal lesions associated with lead toxicity in a young growing
animal. The excellent quality gross image and radiographs provided by the
contributor nicely demonstrate the thick band of sclerosis present in the
metaphysis, known as the lead line mentioned above. Normally, growth of the
bone at the metaphysis is the result of an orderly balance between osteoblastic
deposition of bone and osteoclastic bone resorption at the zone of provisional
calcification in the physeal zone of hypertrophy and primary spongiosa.4,11
The majority of lead is stored within osseous tissues of the skeleton, and lead
ions will preferentially deposit within the metaphysis and directly inhibit
osteoclastic activity at this location.16 As a result of this
impairment of osteoclastic resorption of bone within the primary spongiosa,
there is disruption of endochondral ossification and the formation of a growth
retardation lattice.4,11,16 This lattice is composed of elongated
and vertically oriented trabecular bone with persistent cores of mineralized
cartilage within the metaphysis. The sclerotic metaphysis is not radiopaque due
to the lead itself; rather it is a result of calcium deposition and retention of
mineralized cartilage trabeculae within the metaphysis.4,11 As
mentioned by the contributor, other diseases that cause growth retardation
lattices include canine distemper virus (canine morbillivirus) and bovine pestivirus. Both viruses infect osteoclasts resulting in reduced
This case generated spirited discussion among conference participants regarding whether the histologic lesions described in this case are consistent with lead intoxication. Conference participants described a diffusely thickened growth plate with multifocal tongues of cartilage cores extending into the metaphysis with a light blue to pink matrix and surrounded by a necrotic coagulum. Participants also noted few large vacuolated osteoclasts containing up to thirty nuclei within Howships lacuna but were not able to identify intranuclear or intracytoplasmic inclusions noted by the contributor.
Prior to the conference, the moderator, Dr. Linden Craig, examined the long bones of several age-matched control calves without lead intoxication. The consensus opinion of the conference moderator and participants is that there is no significant difference between the amount of mineralized cartilage trabeculae in the calf from this case and an aged matched control animal. This represents a disconnect between the sclerotic metaphysis seen both grossly and radiographically in this case, and the histologic appearance which lacks the significant retention of mineralized cartilage trabeculae within the metaphysis when compared to the rib of age-matched control. Some participants posited that this may be an artifact of decalcification processing of this section. Without the aid of the gross, radiographic, and historical data, diagnosis of lead intoxication in this case is extremely difficult.
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