LAMINITIS 0749---0739/99 $8.00 + .

00

THE PATHOPHYSIOLOGY OF
CHRONIC LAMINITIS
Pain and Anatomic Pathology

Sherry J. Morgan, DVM, PhD,

Deborah A. Grosenbaugh, DVM, PhD,
and David M. Hood, DVM, PhD

The purpose of this and the next two articles in this issue is to describe the
pathologies of chronic laminitis. Categorically, these articles apply to any patient
with radiographic or physical evidence of collapse of the foot. 9 Due to the
variations in clinical presentation and response to therapeutic attempts, these
patients often pose a diagnostic and prognostic challenge that is clearly distinct
from that of the acutely affected horse. These difficulties arise from the variable
presence and complexity of the digital and systemic pathologies that together
serve to establish a patient's clinical statusY
As this topic is addressed, several concepts must be clearly acknowledged.
The first is that chronic laminitis patients have significant variation in presenta-
tion. As the epidemiology of laminitis is better defined,1, 5, 24 it is becoming clear
that many, if not most, chronic laminitis patients are not severely lame. Numer-
ous patients demonstrating radiographic evidence of digital displacement are
capable of significant athletic function and are often undiagnosed. Others are in
such chronic pain that euthanasia is the only humane alternative. The variation
in clinical presentation mandate that each patient be considered as clinically
unique. Multiple reasons for patient variation exist, including the disease dura-
tion, stoicism of the horse, therapeutic regimen, and nature of the digital and
systemic pathologies present.
It must also be accepted that acute laminitis and chronic laminitis are
clinically distinct problems. 9 The horse with acute laminitis, before digital col-

From the Department of Anatomic Pathology, Drug Safety Evaluation, Abbott Laboratories,
Abbott Park, Illinois (SJM); the Department of Animal Health Research and Develop-
ment, Abbott Laboratories, North Chicago, Illinois (DAG); and the Department of
Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas
A&M University, College Station, Texas (DMH)

VETERINARY CLINICS OF NORTH AMERICA: EQUINE PRACTICE

VOLUME 15 • NUMBER 2 • AUGUST 1999 395

396 MORGAN et al

Table 1. OBEl SCORING SYSTEM GRADING OF lAMENESS ASSOCIATED

WITH lAMINITIS

Score Description
Standing horse lifts feet incessantly; when walking, no lameness is seen;
when trotting, the gait is short
II Horse moves willingly at a walk, but gait is characteristic for laminitis;
forefoot can be easily lifted
III Horse moves reluctantly and resists attempts to lift a forefoot
IV Horse does not move without being forced

lapse appears, has relatively few problems in the foot, and treatment is much
simpler. The occurrence of structural failure alters and radically expands the
number of digital pathologies present. This, in tum, leads to necessary changes
in the therapeutic regimens used in rehabilitation efforts.
The broad spectrum of clinical presentations in chronic laminitis patients
implies that some type of patient classification should be employed. Classically,
the basis of such classification has been the degree to which these patients
demonstrate pain20 or the nature and severity of the digital pathologies present. 6
Although it is technically impossible for a human being to adequately assess
pain perception in another species, the severity of lameness present, which is
indexed as the ability or willingness of the horse to voluntarily move or bear
weight on the feet, is commonly used for this purpose. These pain indices are
used to classify disease severity, to assess the response to a given therapy, and
as criteria for euthanasia.
Various systematic approaches have been used to codify the expression of
pain in affected horses. Dr abel's work in 1947'0 delineated what has become
known as the abel Scoring System (Table 1). The Clinical Scoring System13 (Table
2) is an attempt to decrease interpretive problems encountered when multiple
individuals with different sensitivities to animal suffering are asked to describe
the same patient in which systemic analgesic therapies are being used. More
objective lameness evaluation systems have been developed and have proven
useful for the evaluation of therapeutic response. 1O,13
In addition to these indices, a further classification has been proposed by
which the overall status of the patient can be better described. In this system,
patients can be described as being "compensated" or "uncompensated" and as
"progressive" or "static."l1, 13, 14 The degree of compensation in a patient is an
effort to separate and identify patients based on their overall clinical status,
irrespective of the physical, radiographic, gross, or histologic disease present in

Table 2. CLINICAL SCORING SYSTEM OF LAMENESS ASSOCIATED WITH LAMINITIS

Score Description
CS-l Horse is capable of full athletic function
CS-2 Horse is capable of minimum pleasure riding but not full athletic function
CS-3 Horse cannot be ridden but is usable for breeding or can be maintained
pasture sound with minimal use of systemic analgesics
CS-4 Horse must be maintained on systemic analgesics to function
CS-5 Horse must be euthanatized due to severe unresponsive pain
 THE PATHOPHYSIOLOGY OF CHRONIC LAMINITIS 397

the foot. For example, a horse that is relatively sound, despite significant rota-
tional or vertical displacement of the distal phalanx, would be considered to be
a compensated patient. Likewise, the severely lame patient with perhaps little
radiographic pathology would be considered to be uncompensated. The progres-
sive versus static descriptors serve to identify the patient whose clinical status
is or is not changing.
The relative degree of compensation and progression are useful in defining
the relative goal and risk associated with rehabilitation efforts. This is especially
true when considering the horse's intended use. For example, the laminitic
broodmare that is fully compensated and static might be considered a poor
risk for rehabilitation, as such effort could result in temporary or permanent
progression to an uncompensated state. Alternatively, rehabilitation of the per-
formance horse with the same initial clinical classification might be attempted if
its primary value is in its athleticism.

PAIN IN THE HORSE WITH CHRONIC LAMINITIS

Because the magnitude of perceived pain in the horse with laminitis is used
as a criterion of disease severity and response to therapy, it seems logical to
address its origin and the problems associated with its use. Digital pain in the
chronically affected horse has several potential origins. These include elevated
levels of inflammatory mediators, increased submural pressure, repeated trau-
matic tearing of the submural tissues, excessive contact at the solar surface of
the distal phalanx, fractures, abnormal stresses placed on tendons and ligaments,
sepsis, and ischemic episodes.
Central to the pain in the chronically foundered horse is that originating
from the accumulation of inflammatory factors in the foot. Although it is as-
sumed that the inflammatory cascades present in the horse are similar to those
in other species, the specific mediators involved in the horse's foot have not
been fully elucidated. The reduction of lameness following the appropriate use
of nonsteroidal anti-inflammatory drugs (NSAIDs)l1 bears witness to the fact
that the prostaglandins are involved. It should be noted that in the horse with
chronic laminitis, the response to NSAIDs is not the same as that in the horse
with an acute injury. It takes some 3 days for the analgesic effects to reach
maximum effectiveness. Similarly, 3 days are required for the pain to fully
return following discontinuation of therapy. Intuitively, this period is required
to effectively alter NSAID tissue concentration and the inflammatory reactions
or the plasticity of the nervous system with regard to pain (see below).
Increased submural pressure as a soure of digital pain is easily conceived
from the clinical response to relieving such pressure. Draining an abscess, for
example, provides an immediate and significant decrease in pain. There are
multiple potential causes of increased submural pressure in chronic laminitis.
The edema that accompanies inflammation or alterations in circulatory dynamics
is often present16, 18, 22 as is the hemorrhage into the submural dermis that
accompanies trauma to the weakened lamina. Seroma formation or abscessation
represents a potentially treatable cause of increased submural pressure, although
diagnosis and localization are often difficult.
Submural hemorrhage in the horse in the chronic phase of laminitis is often
the sequela of traumatic tearing of the foot's submural tissues. Such tearing
involves nerve fibers as well as vascular and collagen fibers, causing stimulation
and pain. This trauma also induces an inflammatory response that serves as a
further cause of pain. As is discussed in the article on the mechanisms and
398 MORGAN et al

consequences of structural failure of the foot in this issue, digital instability

appears to be more related to the expressed pain and clinical status than is the
magnitude of displacement of the distal phalanx. In this concept, the laminar
interface, weakened by the primary insult and type 'of healing response that is
occurring, allows this tissue to have a reduced ultimate strength that cannot
withstand the loads placed on iU
The foot's mechanical failure, resulting in displacement of the distal pha-
lanx, increases the magnitude and constancy of the contact between the internal
surface of the sole and the bone." 10 This increased contact elevates pressures,
particularly against the bone's peripheral edges, generating pain. Support for
this concept includes the immediate relief that can be realized as the pressure
against the sole is ameliorated by shoeing. Likewise, the increased lameness that
occurs when a heart bar shoe is applied with excessive pressure against the sole
further supports the fact that elevated bone pressure is a source of pain in these
patients. Pain arising from this pressure seems to decrease as bone remodeling
occurs.
Ischemia as a cause of pain is also possible in chronic laminitis, where the
foot's vasculature system is affected in a number of ways.B, 10, 13 As is discussed
later in this article, the foot's circulation is affected by compression of the solar
circulation, tearing of the submural vessels, and a vascular hypersensitivity.
Transient ischemic episodes followed by reperfusion result in pain and serve as
an additional cause of inflammatory pain.
Given the fact that pain in these patients is multifactorial, it is logical that
the use of NSAIDs alone is sometimes inadequate to effectively limit patient
discomfort. Rationally, NSAIDs are partially successful in most cases, as an
inflammatory response is a consequence of other mechanisms. It is therefore
reasonable that the source of pain should be investigated and treated accord-
ingly.
There are several inherent problems associated with the use of perceived
pain as an index of disease severity. At the root of most of these is the technical
problem that pain is something that the horse senses and that what is being
used in grading is man's perception of what the horse is sensing. This allows
for a considerable interpretative range, because just as not all horses express
pain to a uniform degree, not all human beings have the same perceptive powers
or frame of reference for interpretation. In addition, several problems arise from
misperceptions regarding the use of pain indices and misinterpretations of pain
in the chronic laminitis patient.
A common misperception is that the perceived pain relates directly to
disease severity. Experience dictates that this relationship, although generally
true, is not always the case. Specific patients can have a combination of digital
pathologies that precludes any hope of successful rehabilitation, yet they demon-
strate little lameness. Such a situation might occur when the digit develops a
gangrenous pathology (the truly marvelous thing is that it no longer hurts). The
opposite case is likewise true; the horse may have only relatively mild organic
changes in the feet but demonstrates a relatively severe lameness. This most
often occurs as a function of disease duration; patients often display a greater
lameness early in the course of the disease.
A second misconception regarding the severity of lameness is that its reduc-
tion always reflects therapeutic success. The best example of this is the immedi-
ate but usually temporary decrease in lameness that can be realized by un-
loading the entire sole by elevating the wall with a rim shoe. Decreased lameness
is often observed, as the solar edges of the distal phalanx are unloaded. This
effect is often short-lived, as the foot, in the absence of solar support, merely
 THE PATHOPHYSIOLOCY OF CHRONIC LAMINmS 399

collapses, further increasing long-term problems. Another way to look at this

concept is to state that rehabilitation can result in or involves an increase in
patient discomfort at times.
The second difficulty associated with the use of perceived pain as an index
of disease severity is that of correctly interpreting the meaning of changes in
stance or gait. The classic description of the foundered horse's stance has long
been interpreted to reflect the horse's effort to shift a percentage of its weight to
its rear feetY Studies employing force plates and pressure mats have indicated
that it is difficult for a laminitic horse to shift significant amounts of weight
from the front limbs to the rear limbs. '2, 13 Instead, these patients maintain the
same mean load on the forelimbs as sound horses but increase the frequency of
alternatively loading and unloading the contralateral limbs. Further studies
(D. M, Hood, unpublished data) indicate that the purpose of the stance is to
preferentially load the heels rather than the toes of affected forefeet. 4,21
A second example of an interpretive problem is the assumption that in-
creased weight bearing on a foot reflects decreased pain, Clinically, this problem
arises when a severely affected horse that has been bearing weight on one
forefoot suddenly shifts the weight to the other. Rather than this representing
decreased pain in the loaded foot, this most often reflects increased pain in the
nonloaded foot. This loading pattern often reflects a debilitating cycle in which
the loaded foot is damaged by the applied load, subsequently collapses, and
becomes more painful. This causes the horse to shift load to the opposite
forelimb, where the cycle repeats itself.
Alternatively, there are instances in which an altered gait is incorrectly
interpreted as pain. The foundered horse in which the heels have been allowed
to grow to excessive lengths or in which the flexor tendons have contracted may
be unwilling to walk for biomechanical reasons, that is, the relative positions of
the pasterns and fetlocks are so altered that the horse cannot walk normally.
Rehabilitation efforts directed at gradually shortening the heels and lengthening
the tendons are much more effective than increasing the level of analgesic
therapy in these patients.
It should not be forgotten that pain can serve as a pathology. In the
chronically affected horse, it is the principal cause of stress and hypertension
and must be considered as contributory to the gastric ulceration that is usually
associated with long-term use of NSAIDs, In the digit, chronic pain often results
in a secondary contracture of the hoof and the flexor tendons due to the horse's
unwillingness to load the foot.
Furthermore, recent advances in understanding chronic pain treatment have
led to the concept that pathological pain begets pain. Mechanistically, this is
thought to be secondary to the repeated stimulation of primary sensory nerves
inducing a sensitization of spinal cord neurons. This results in hyperalgesic and
allodynic states, making efforts to control pain more difficult. Thus, the horse
responding to treatment for chronic laminitis might not show the same response
to systemic analgesics as the horse with acute laminitis.

GROSS PATHOLOGIES OF THE LAMINITIC FOOT

The gross alterations in the foot affected with chronic laminitis are highly
variable. At one end of the spectrum, the affected foot may demonstrate minimal
changes, although at the other extreme, a totally gangrenous foot may develop.
Between these extremes, individual patients demonstrate variations caused or
influenced by the regional distribution of the pathologies, the duration of the
400 MORGAN et al

disease, and the type and invasiveness of the treatments applied during rehabili-
tation efforts. For the most part, these gross pathologies are acquired lesions.
Externally, the wall can appear to be relatively normal in chronic laminitis.
The only detectable external change may consist of a slight widening of the
white line, a dropped or flattened sole, and a slightly upright foot. These horses
are often fully compensated clinically, and it is often necessary to employ
radiographs to confirm the presence of disease. More marked morphologic
patterns include alterations of the wall, sole, and coronet as well as those that
involve the foot as a unit. These more severe morphological changes fall into
several general patterns which vary according to disease duration and severity.6
A prevalent wall abnormality is founder rings (Fig. lA). These are repre-
sented as small ridges running from heel to heel that are farther apart at the
heels than at the wall's dorsal surface. The divergence of these rings results
from a differential growth rate in which heel growth in affected feet exceeds
that of the dorsal wall.23 In addition to the rings, the wall often displays single
or multiple transverse cracks that originate at the coronet and grow distally over
time. These alterations originate at the coronary band, where the wall is formed.
It is unclear if these defects result from mechanical forces acting on the coronary
papillae or from repetitive metabolic or vascular insults imposed on the germina-
tive layers of the coronary epithelium.
The dorsal wall of affected feet often assumes a concave shape that can be
severe at times. This wall malformation is attributed to a combination of the
unequal rate of growth of the dorsal wall relative to that of the heels and the
effects of the mechanical forces being imposed on the wall. In the untrimmed

Figure 1. Common morphologic changes in chronically affected foot. A, Presence of

founder rings. B, Acute change in angle of dorsal hoof wall and long heels.
 THE PATHOPHYSIOLOGY OF CHRONIC LAMINITIS 401

foot, long and underrun heels often accompany this acquired wall conformation
(see Fig. IB). A second frequent malformation consists of an acute change in the
angle of the dorsal wall. This angle change reflects a healing response in which
rotational displacement has become decreased in the more proximal regions of
the foot (see Fig. IB).
Changes in the coronary band region are frequent and appear to vary with
disease duration and severity. Early in the course of the disease, the soft tissues
just proximal to the coronet may appear to be swollen and edematous. IS As the
foot collapses, this region often acquires a depression as the distal phalanx
displaces relative to the wall. 6 This coronary depression may extend for variable
distances toward the heels and may persist as the disease becomes more chronic.
Alterations of the sole range from being nearly normal to pronounced (Fig.
2). At its mildest, only a widening of the white line regions can be noted,
reflecting the fact that the terminal papillae of the foot have been affected. This
change is often accompanied by a flattening of the sole, reflecting ventral
displacement of the distal phalanx. In more severe cases, the solar surface is not
flat but instead demonstrates an irregular dropping directly under the descend-
ing edge of the distal phalanx. At its most severe, the entire solar surface is
displaced below the level of the bearing wall.
A loss of the sole's structural integrity can occur, appearing as a defect sited
between the tip of the frog and the white line. Characteristically, there is little
drainage present when this defect first appears. In most of these cases, a fully
cornified sole is present deep to the defect, and the defect is of little clinical
consequence (Fig. 3). This is designated as a "false sole" and reflects a normal
healing response. Alternatively, perforation of the sole may also reflect an ab-
sence of solar healing or regeneration secondary to pressure necrosis. In these
instances, a granulation bed or bone is present in the solar defect (Fig. 4).
Chronic disuse of the foot resulting from digital pain often leads to a
contracture of the hoof and digital flexor tendons. Both of these changes are the
direct result of the principle that the wall and tendons require periodical applica-
tion of loads to maintain optimal conformation and length. Contracture of the
foot or flexor tendon can lead to pain and a physical inability to walk. Both of
these topics are currently the focus of rehabilitation research.
Variable but characteristic changes of the foot's internal structure often
accompany these external changes. The most obvious of these is displacement
of the distal phalanx relative to the wall, which is usually described as being
either rotational or vertical. Rotational displacement is the disproportional move-
ment of the dorsal parietal surface of the phalanx away from the wall so that its
distal free edge is removed farther from the external wall than is its proximal
surface (Fig. 5). Rotational displacement can be subdivided into capsular or
phalangeal displacement (the reader is referred to the article on the mechanisms
and consequences of structural failure of the foot in this issue). Vertical displace-
ment, or sinking, is the uniform palmar displacement of the distal phalanx. In
cases of pure vertical displacement, the bone's dorsal parietal surface and dorsal
hoof wall remain parallel (see Fig. 5).
In either type of displacement, it is stated that the distal phalanx'S move-
ment is relative to that of the hoof wall. This implies that the wall may, in fact,
be moving as much and at the same time as the distal phalanx. What is seen
physically and radiographically is the summated displacement of the two. The
mechanics and consequences of these two types of displacement are discussed
in the article on the mechanisms and consequences of structural failure of the
foot in this issue. Here, only the general morphologic features are addressed.
Grossly visible hyperproliferative, traumatic, or necrotic changes of the
laminar interface necessarily accompany displacement of the distal phalanx. The
Figure 2. Common morphologic changes on the solar surface of foot affected with chronic
laminitis. A, and B, Widening of white line (arrows). C, Flattening of sole. 0 , Presence of
large, deep solar defect (arrow) anterior to point of the frog .

402
 lHE PATHOPHYSIOLOGY OF CHRONIC LAMINITIS 403

Figure 3. Solar surface depicting a false sole. A and B are different in that more sole has
been trimmed in B. Arrows depict margins of external sole. Deep to the defect, a second,
fully cornified sole is present.

degree of laminar proliferation, a healing response, is highly variable, and it

mayor may not be proportional to the degree of rotational displacement. Figure
6 depicts a case in which the proliferation is proportional to the rotation. In this
case, the rotation is of such severity that there is penetration of the sole. Con-
versely, there are cases (Fig. 7) in which laminar proliferation does not parallel
the degree of displacement. This sometimes reflects traumatic tearing of the
laminar interface due to its decreased strength.

Figure 4. Proliferative granulation bed present in a solar defect, commonly occurs second-
ary to pressure necrosis of subsolar dermis/epidermis.
404 MORGAN et al

Figure 5. Rotational (A) and vertical displacement (8) of distal phalanx relative to the wall.
Note horse with rotational displacement also demonstrates vertical displacement.

Locally extensive regions of necrosis often occur within the hyperplastic

laminae. Figures 8 and 9 depict regions of such necrosis, which are represented
as draining tracts or abscesses with tracts. As indicated in the section on histo-
logic changes, the regions of necrosis may reflect tissues destroyed in the initial
insult, excessive pressures, or poor vascular perfusion. Alternatively, a primary
or secondary bacterial involvement cannot be ruled out, particularly in a horse
with a poor-quality sole.
The distal phalanx exhibits several morphologic and radiographically visible
changes, including localized regions of necrosis (see Fig. 8), fractures, an altered
contour (see Fig. 9), and changes in radiographic density. Bone necrosis and
fractures resulting from compromised vascular perfusion and excessive pres-

Figure 6. Sagittal section of chronically affected foot showing hyperproliferative response

of the laminar interface. Note proportionality of degree of rotation and laminar hyperplasia.
Foot also demonstrates vertical and rotational displacement, submural and subsolar separa-
tion of dermis, sunken coronary band, and perforation of the sole.
 THE PATHOPHYSIOLOGY OF CHRONIC LAMINITIS 405

Figure 7. Chronically affected foot. Degree of rotation is more pronounced than the laminar
hyperplasia. Portion of laminar interface remains attached to the zona alba of the wall.
Radiographically, foot would demonstrate a large submural air space and solar air line.

Figure 8. Chronically affected foot. Note necrosis of tip of the tip of the distal phalanx with
sequestrum formation and proximal (coronary) separation of the wall, and separation of the
distal lamina from the sole. Clinically, these may represent shear lesions, pressure necrosis,
or sepsis (draining tracts).
406 MORGAN et al

Figure 9. Chronically affected foot. Note blunted irregular contour of distal phalanx as well
as multiple intercommunicating tracts involving hoof wall, hyperplastic laminar tissue, and
sole regions. Osteomyelitis was suspected on radiographic and gross examination, and
confirmed with histologic examination. Irregular air spaces are often visible on radiographs.
Sagittal section demonstrates several lying in partially cornified submural and subsolar
regions (large arrows) representing potential communications to viable regions of the foot.
Space lying adjacent to parietal surface of the distal phalanx (small arrows) poses a greater
threat to the horse because of its proximity to the bone.

sures being placed on the bone can be visualized. Common bone contour
changes include a flattening of its solar surface, development of a concavity of
the dorsal surface, and exostosis. Characteristically, the tip of the distal phalanx
demonstrates exostosis (lipping), reflecting periosteal new bone proliferation
secondary to mechanical instability or periostitis, or a loss of bone. The loss of
bone from this area is subsequent to disuse, impaired blood supply, excessive
pressures on the sole with abnormal stress distribution, or a more clinically
significant osteomyelitis. Additionally, the primary vascular channels in the bone
may appear to be widened on radiographs. This is thought to be a change
occurring secondary to the altered blood flow created by digital collapse.
The displaced distal phalanx, especially when rotational displacement is
significant, induces changes in the coronary, laminar, and solar soft tissue inter-
face. In the dorsal regions of the foot, these include a widening and redirection
of the coronary band and terminal papillae epithelium as well as a decrease in
the area of laminar interface (Fig. 10). Changes also occur in the quarters, heels,
and soft tissues between the inner surface of the sole and distal phalanx, where
the predominant gross lesion is that of pressure necrosis. These changes result
from a combination of the altered patterns of growth and metabolism, the
attempts of the foot to heal, or as a consequence of either the initial insult or
the collapse of the foot. These changes are presented and discussed in other
articles in this issue.

RADIOLUCENT AIR LINES AND AIR SPACES IN THE

CHRONIC LAMINITIS PATIENT

One of the variable morphologic gross or radiographic findings in chronic

laminitis is the presence of air-filled spaces in the submural or subsolar region. 25
 THE PATHOPHYSIOLOCY OF CHRONIC LAMINITIS 407

Figure 10. Sagittal section demonstrates a widened coronary band, change in angle of the
coronary band papilla, decreased laminar interface, and a widened white line.

The clinical implications of these vary significantly according to their location

and their time of appearance. The most serious of these are the acute Type I air
lines that develop within 20 to 40 hours of the initial onset of lameness. This
type of air line represents acute separation of the dermal-epidermal interface
secondary to the combination of enzymatic activity, necrosis, and the mechanical
forces being placed on the foot. These early air lines are characterized by physical
disruption of the coronet, which appears to be the principal source of air.
The pathologic significance of these early air lines lies in the fact that they
represent separation of the hoof capsule from its attachments to the foot. This
separation is not initially total, as regional attachments still remain in the heel
and solar regions. Separation can become total, resulting in the sloughing of the
hoof capsule. Horses in which this occurs can be rehabilitated, but it is rarely
attempted for humane and economic reasons in light of a low incidence of suc-
cess.
These early air lines are distinct in origin and seriousness from those that
appear more slowly, beginning some 12 to 14 days after the initial lameness in
either the submural or subsolar region. 25 These characteristically appear in the
middle third of the dorsal wall as a narrow linear translucency, gradually spread
both proximally and distally toward the coronary and solar surfaces, and have
no obvious communication with the foot's exterior surface; these are termed
Type II air lines. Histologically, the tissues involved are the most peripheral
parts of the laminar interface and represent mummified epidermal structures
(Fig. 11). Architecturally, these air spaces extend both laterally and medially
around the wall and are diagnosed in the dorsal regions because of the lateral
position used for the radiographs.
Until this air space gains access to the exterior of the foot as a consequence
of growth, no bacteria are observed histologically. Mechanical testing indicates
that this type of air line does not represent a source of digital instability or
408 MORGAN et al

Figure 11. Type II air line (arrows) in a standard lateral view (A), sagittal view (B), and
transverse view (C) made using thin-section radiographs.

weakness.25 Thus, this type of air line is not of major significance to the affected
horse and disappears as it grows out the solar surface of the foot. The relative
position of these air lines can sometimes be useful in estimating the time of
onset of an acute episode of laminitis, as they grow out at a rate consistent with
that of the hoof wall.
The third category (Type III air lines) are represented by a large irregular
space located in the submural or solar area of the foot (Fig. 12), which appears
relatively late in the clinical course of the disease, usually when significant
displacement of the distal phalanx is present. These frequently occur without
evidence of communication with the foot's external surface but invariably estab-
lish communications as the foot grows. Dissection of this pathology indicates
that a majority represent mechanical failure of hyperproliferative laminae sec-
ondary to loading forces. The abrupt appearance and irregular shape of these
spaces relate to rapid tissue contraction as it pulls free from the interior surface
of the wall. These larger air spaces often represent a significant decrease in
digital stability.
Solar air lines and air spaces are also common but are less well described.
Most often, these appear to be similar to those that appear 12 to 14 days
postinsult, that is, they are the product of the initial disease and do not commu-
nicate with the exterior until growth and wear invade the space. In some cases,
these represent a false sale, as the foot's healing response has resulted in a
relatively normal sale deep to the space.
The relationship between these air spaces and the introduction of infection
is not clearly established. As the air spaces gain exposure to the exterior of the
 THE PATHOPHYSIOLOGY OF CHRONIC LAMINITIS 409

Figure 12. A and B, Large Type III air spaces in the submural space. This space visible
(A), reflects pathology seen in Figure 7.

foot, they undoubtedly become contaminated. If these areas are maintained

under moist conditions, they rapidly develop an odor and a small amount of
drainage. Because of their origin, however, these spaces often lie between what
is essentially two layers of fully cornified tissues formed during the healing
response. In these cases, microflora represent contamination rather than infec-
tion. Alternatively, these spaces represent potential sources of sepsis or routes
for drainage from infected regions within the foot.

HISTOPATHOLOGY OF CHRONIC LAMINITIS

A complete understanding of laminitis involves not only the clinical and

physiologic aspects of the disorder but also a basic knowledge of the pathologic
changes that occur. The basis for such an understanding requires an appreciation
of the normal foot's gross and histologic anatomy. The hoof wall consists of
three basic divisions identified as (1) the stratum externum, (2) the stratum
medium, and (3) the stratum internum, which is also known as the stratum
lamellum (Fig. 13). These variably cornified layers overlie the corium or dermal
410 MORGAN et al

Figure 13. Sagittal (A) and transverse (8) section of foot depicting stratum externum (A),
stratum medium (8), stratum internum (C), and submural dermis (D).

layers of the foot, the component that is comprised primarily of connective

tissue and contains the foot's vasculature and nerve supply. The corium is
continuous with the integument of the limb and is named in accordance with
the location in which it is found (i.e., periople, coronary, sole). The germinal
epithelium of the perioplic corium produces the stratum extern urn, whereas the
germinal epithelium of the coronary corium produces the bulk of the stratum
medium. The stratum internum serves to attach the visceral surface of the wall
to the corium overlying the parietal surface of the distal phalanx. This layer is
architecturally arranged as an ornate laminated surface involving both epidermal
and dermal components and can be described as the laminar interface. It is this
laminar interface from which the term laminitis is derived.
Histologically, the laminar interface consists of a folded and refolded epider-
mal-dermal surface separated by a basement membrane that serves to vastly
increase the surface area for attachment of the hoof to the axial skeleton.
Morphologically, these elements are identified as to composition (epidermal or
dermal) and architectural level (primary or secondary) (Fig. 14). The degree of
 THE PATHOPHYSIOLOGY OF CHRONIC LAMINITIS 411

epidermal cornification varies within this structure. The secondary epidermal

laminae consist of basal and spinous epithelial cells that are poorly cornified,
whereas the primary epidermal laminae consist of transitional epithelium at a
much higher level of cornification. The normal structure and orientation of the
laminar interface is illustrated in Figure 14.
Although the focus of this article is on chronic laminitis, an understanding
of the morphologic changes noted in its precursor, acute laminitis, is important
to the understanding of the chronic disorder. Additionally, many horses with
chronic laminitis have periodical clinical and histopathologic manifestations of
acute disease, particularly those that are classified as being uncompensated and
progressive; as such, they could be more appropriately classified on a pathologic
basis as having "chronic active" rather than "chronic" laminitis.
The primary histologic finding in acute laminitis is a variable degeneration
or necrosis of epidermal cells. lB• 22 The epidermal laminae may exhibit extensive
regions of necrosis or scattered necrotic cells primarily isolated within the sec-
ondary epidermal laminae. This necrosis tends to be more severe in peripherally
oriented (adjacent to the wall) rather than in axially oriented secondary epider-
mal laminae. Extensive vacuolation of both primary and secondary epidermal
laminar cells may also occur. Edema of the epidermal-dermal junction may
accompany cases with extensive regions of epidermal necrosis (Fig. 15).
Investigations using an ischemic/reperfusion laminitis model (D. M. Hood,
unpublished data) indicate that laminar epithelial necrosis is present within 4
hours of reperfusion as well as the appearance of discomfort, implying that

Figure 14. Histology of laminar interface made at two magnifications demonstrate primary
epidermal lamina (PEL), secondary epidermal lamina (SEL) composed of basal and spinous
epidermal cells, and primary and secondary dermal lamina (PDL and SDL). (Hematoxylin-
eosin, original magnification x 20 and x 200, respectively.)
412 MORGAN et al

Figure 15. Histologic appearance of laminar region from a horse with acute laminitis. Note
extensive necrosis of SEL (arrowheads) and edema with separation at dermal--epidermal
junction (hematoxylin-eosin, original magnification x 100).

when clinical laminitis is first evident, there is likely to be epithelial necrosis.

The weakening or disruption engendered by these degenerative laminar changes
predisposes to failure of the laminar interface, and the likelihood of digital
displacement is thus proportional to the severity of laminar necrosis. Hemor-
rhage is a variable finding that may be characterized by relatively focal aggre-
gates of red blood cell extravasation in the dermal laminar regions or may be
extensive with involvement of both the dermal and epidermal laminae.
These acute histologic changes can resolve or progress toward a spectrum
of changes as the disease becomes chronic. The hallmark of the histologic
changes noted in chronic laminitis is the degenerative and dysplastic changes of
the primary and secondary epidermal laminae. Degenerative changes, including
epithelial vacuolization or necrosis and dermal-epidermal vacuolation and
edema (Fig. 16), although more consistently a feature of acute laminitis, are
variably present in chronic laminitis. These changes reflect exacerbation of the
chronic disease and potentially reflect progression to an uncompensated clinical
state. These changes more typically involve secondary epidermal laminar cells,
but the primary epidermal cells may be affected as well.
Dysplastic changes in the chronic disease include a widening, fusion, short-
ening, or loss of either the primary or secondary epidermal laminae (Figs. 17
and 18). Architectural changes are principally restricted to secondary epidermal
laminae when the pathology is mild, with involvement of primary laminae
occurring with increased severity. Widening and fusion of the laminae are
histologically characterized by a variable and irregular epithelial hyperplasia.
Characteristically, hyperplasia of the primary epidermal laminae tends to be
more pronounced peripherally (adjacent to the stratum medium), whereas sec-
ondary epidermal hyperplasia predominates in laminae nearer the distal pha-
lanx. These architectural changes necessarily decrease the laminar surface area,
weakening the foot's structural integrity. Extensive primary epidermal widening
 lHE PATHOPHYSIOLOGY OF CHRONIC LAMINITIS 413

Figure 16. Histologic appearance of laminar region from a horse with chronic laminitis.
Note thickening and fusion of PEL with diffuse vacuolization of epidermal laminar cells
(hematoxylin-eosin, original magnification x 40).

may also impinge on space normally occupied by the primary dermal laminae,
predisposing to compression of the laminar microcirculation.
An additional architectural change noted in the primary epidermal or der-
mal laminae is elongation; this change may occur alone or with the histologic
changes described above. Lengthening of the primary epidermal or dermal

Figure 17. Histologic appearance of laminar regions of a foot with chronic laminitis. Note
hyperkeratinization of PEL (arrows) and extensive loss, fusion, and thickening of SEL
(hematoxylin-eosin, original magnification x 40) .
414 MORGAN et al

Figure 18. Histologic appearance of laminar region from a horse with chronic laminitis.
PEL hyperkeratinization is present. In addition, there are focal regions of necrosis (arrows)
and SEL are practically unrecognizable (hematoxylin-eosin, original magnification x 100).

laminae is a hyperproliferative response and is the histopathologic correlate to

the radiographically or grossly detectable wedge of tissue that is present between
the dorsal hoof wall and the third phalanx. One pattern of laminar elongation
consists of a proliferative response occurring at the peripheral aspects of the
laminar interface. In some horses, this appears as proliferative caphorn, in
others, it appears to be associated with tubular and intra tubular horn being
added to the zona alba of the stratum medium (Fig. 19).2, 19 The mechanisms of
this process are still under investigation. If these laminae have accompanying
dysplastic changes in the secondary epidermal laminae, normal laminar strength
is not possible.
Laminar proliferation often demonstrates a variable degree of cornification
(see Figs. 17 and 18). As discussed in the article on the digital pathologies of
chronic laminitis in this issue, such cornification may provide some degree of
stability to the laminar interface. Histologically, cornification widens the primary
epidermal laminae. Intuitively, if extensive, cornification of the primary epider-
mal laminae may result in a significant impingement of the vascular supply of
laminar microcirculation.
Disruption of the vascular supply is of importance in the pathogenesis of
the chronic as well as the acute disease. Despite the in vivo evidence of vascular
compromise, significant histologically detectable vascular changes (such as
thromboses or vascular necrosis) are infrequently detected in horses with chronic
laminitis. When vascular thrombosis is detected, it generally consists of loosely
arranged fibrin thrombi only; organized occlusive thrombi, which would be
expected to result in considerable vascular disruption, are extremely rare.

CORRELATION OF CLINICAL STATUS WITH

HISTOPATHOLOGY
The results of preliminary studies correlating the severity of histologic
changes and lameness severity indicate that as expected, relatively limited his to-
 THE PATHOPHYSIOLOGY OF CHRONIC LAMINITIS 415

Figure 19. A, and B, Histologic sections from peripheral laminar interface from two horses
with chronic laminitis. Both sections demonstrate elongation of laminar interface created by
a cornifying hyperplasia (hematoxylin-eosin, original magnification x 40).

logical change is associated with a low degree of lameness. Mildly affected

patients typically displayed minimal to moderate epidermal histopathology con-
sisting of necrosis, vacuolation, and dysplasia (shortening, loss, fusion, or widen-
ing) largely restricted to the secondary epidermal laminae; only rarely were
minimal or mild dysplasias of the primary epidermal laminae evident. Dermal
changes in this group consisted of dermal-epidermal vacuolation, dermal infil-
tration, and dermal vascular changes.
Horses with a moderate degree of lameness consistently have more signifi-
cant involvement of the primary epidermal laminae; the necrosis, vacuolization,
and laminar dysplasias are characteristically mild to moderate. Moderately lame
horses demonstrate involvement of the secondary laminae similar to, although
slightly more severe than, that of less clinically lame horses. Severely lame
horses reflect histologic changes in the primary epidermal laminae similar to
those of a moderate clinical score but show a significant increase in the second-
ary epidermal laminar pathologies. Interestingly, the degree of laminar prolifera-
tion (elongation) and widening is highly variable and does not appear to vary
with lameness severity, implying that these measurements are not a reliable
index of clinical status whether they are made from tissue sections or radio-
graphs.
The question of whether or to what extent the laminar morphology could
return to normal is of considerable importance. The potential for histologic
reversibility is multifactorial depending on the severity of the initial insult and
the success of rehabilitation to normalize the mechanical, vascular, and metabolic
pathologies present. Because all affected horses, even those that appeared sound,
416 MORGAN et al

had dysplastic changes, it follows that efforts to minimize excessive digital loads
are important in all affected horses, regardless of the patient's radiographic
appearance or clinical score.
Ultimately, it is the strength and relative elasticity of the laminar interface
that is critical. Radiographically detectable displacement or laminar thickness is
not a reliable indicator of laminar change. Thus, although radiographically the
third phalanx may return to a normal or near-normal angle, the strength of the
laminar interface is questionable in any horse that has had significant architec-
tural changes in the past.

ACKNOWLEDGMENT

The authors wish to thank Dr Kevin C. Nelson for his critical review of this manu-
script.

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