Department of pathology

Faculty of Veterinary Medicine

Cairo University

Dr Sahar Samir Mahmoud

Special Veterinary Pathology

Course (401)

Musculoskeletal

System

Myopathy

Non inflammatory degeneration and/or Necrosis of

skeletal and cardiac muscles. 1-Nutritional

2-Exertional

3-Viral 7-Neurogenic

6-Ischemic

5-Toxic

4-Chemical

Types (causes)

Deficiency of vitamin E and / or selenium in young

calves and foals. Muscular inactivity during periods of rest after heavy

continuous work “usually a Monday morning”.

In new born calves, sheep and goats “Akabane

and Foot & mouth disease virus infection”. Caused by chemical agents as drugs,food

additives, local anesthetics and antibiotics.

Caused by plant toxines “Solanum malacoxylon “

and mycotoxines “Tremorgenes in Penicillin and

Aspergillus”.

In cattle following recumbency for long period.

following traumatic injury and severance of the

nerve supplying the muscles.

8-Endocrine

9-Traumatic

10-Congenital

Following hyper adrenocortisism in animals and

hypothyroidism in dogs. Following bruising, laceration, gun shot and violent

injection.

Observed in cattle and pigs

Grossly

1- Nutritional muscular dystrophy

Nutritional myodegeneration – White muscle disease

Nutritional disease of calves, lambs and piglets, occasionally

of other animals characterized by coagulative necrosis of

cardiac and skeletal muscles particularly those of thigh, back

and neck.

Causes Vitamin E and / or selenium deficiency.

Heart Skeletal muscle

Hydropericardium

Presence of white

opaque streaks on

the myocardium.

Affected areas have a white

waxy swollen appearance

‘fish flesh”

Presence of white opaque

calcified areas.

Grossly

Nutritional muscular dystrophy

Nutritional myodegeneration – White muscle disease

Nutritional disease of calves, lambs and piglets, occasionally

of other animals characterized by coagulative necrosis of

cardiac and skeletal muscles particularly those of thigh, back

and neck.

Causes Vitamin E and / or selenium deficiency.

Heart Skeletal muscle

Hydropericardium

Presence of white

opaque streaks on

the myocardium.

Affected areas have a white

waxy swollen appearance

‘fish flesh”

Presence of white opaque

calcified areas.

Lesions vary from hyaline degeneration to myonecrosis

c.

Pathogenesis

Areas of calcification may be present.

Micro

a.

Muscle fibers are first red ,homogenous esinophilic

with pyknotic nuclei, later become invaded by

macrophages, undergo lysis and replacement by

fibrous tissue.

b.

Vit E and selenium are both protect the cellular

membranes from free radicals which cause

peroxidation of the membrane lipid by scavenging

those radical.

lipoperoxidation of cell membrane

of muscle fibers

Defective cell membrane

Influx and accumulation of calcium in

the mitochondria

Damage of mitochondria and become unable to

supply energy to the cell

Cell death

Deficiency of vitamin E and / or selenium

A disease of horses characterized by coagulative

necrosis of heavy muscles of shoulder and thighs.

Occurs in horses as equine paralytic myoglubinurea“azoturea “

and in sheep chased by dogs and in cattle after running wildly.

2- Exertional or post- exercise myopathy

Equine rhabdomyolysis

Azoturea, Monday morning disease , tying up syndrome

It is common in days following periods of rest after

heavy continuous work “usually a Monday morning”.

It appears suddenly after few steps, the horse becomes

unable to move, stands still, trembling, sweating in

severe pain.

Affected muscles are swollen and as hard as wood.

Grossly

Affected muscles are pink, then dark red, moist with pale streaks.

Early changes appear as hyaline degeneration of muscle

fibers followed by segmental coagulative necrosis of

small or large groups of muscles.

Myoglubinouric nephrosis appear as degeneration and

necrosis of tubular epithelium of the proximal tubules

with brown casts in the lumina of the distal tubules.

Micro

Pathogenesis

Weekend rest & muscular inactivity

Storage of glycogen in the muscles

As muscles perform work

(Usually a Sunday morning)

Glycogen converted into lactic acid

Muscle irritation

Severe muscle contraction

Muscle hypoxia

Heavy work for a week

Muscle hypoxia

Anaerobic oxidation

Increasing accumulation of lactic acid

Increased spasmodic contractions

of muscles

Severe muscle hypoxia

Degeneration and necrosis

3- Toxic myopathy

Muscles show well defined pale areas and streaks.

Myopathy caused by different types of toxic substances

(plant toxins, mycotoxins, drugs, food additives, local

anesthetics and antibiotics).

Severe muscle hemorrhage and necrosis can be seen

with tetracyclines.

Grossly

Microscopically

Segmental myonecrosis followed by regeneration if the

animal lives.

Deposition of calcium salts in muscles is observed in :

Necrotic muscles (dystrophic).

Muscle calcification

Muscle fibers of old dogs (senility).

Toxic plants containing active vitamin D metabolites

e.g. Solanum malacoxylon (toxic).

Grossly

Glistening white-chalky foci of calcium deposits.

Micro

Bluish deposits with H&E which stain black with Von

Kossa stain.

N.B:

Calcification is often confused with ossification. Calcification is synonymous with the formation of calcium-based salts and crystals within cells and tissue. It is a process that occurs during ossification, but not vice versa.

Interlacing bundles of Connective

tissue. containing dense accumu-

lation of calcium in cartilage and

bone.

Central zone of

mesenchymal-like cells and

fibroblasts mixed with

osteoblasts.

It is the formation of bone tissue that is often atypical, at an

extraskeletal location. Disease of horses, pigs and goats . It

occurs in two forms.

Muscle ossification (Heterotopic Ossification)

Localized form Generalized form

Involves single muscle Involves multiple muscles

Middle zone of osteoid

tissue and immature bone.

Outer zone of trabecular

bone.

Inflammation of muscles which is either non-infectious

or infectious.

Caused by

1- various types of trauma including incisions,

lacerations, perforations and rupture.

2- It may be immune mediated.

3- Idiopathic.

Myositis

Non-infectious myositis

Primary Secondary

Infectious myositis

The micro organisms

specifically invade the

muscles.

The micro organisms

invade the muscles

either:

M.O. accompanying

penetrating wounds.

Clostridial infection.

Actinobacillosis.

Parasites e.g. Sarco-

cystosis, trichinosis,

sarcosporidia

Secondary to systemic

disease e.g. blue tongue,

F&M disease.

By extension of infection

or inflammation from other

lesions as actinomycosis

of mandible.

Bacterial myositis

Bacteria may cause, suppurative, serohemorrhagic or granulo-

matous myositis.

Suppurative myositis

Caused by pyogenic m.o.

Caused by clostridial m.o. That produce two completely different

diseases; Black-leg in sheep and cattle (C. chauvoei) and gas

gangrene in different animals(C. septicum, C. perfringes,

C.nauvoei and C. chauvoei). and characterized by muscle necrosis,

gangrene and serohemorrhagic exudate

Serohemorrhagic myositis

(Streptococcus equi, Actinomyces

bovis, Corynebacterium and Pseudotuberculosis) which

infect the muscle either by direct penetration ( wound

infection) or through blood (hematogenic) producing

localized abscesses.

Parasitic myositis

Helminthic myositis Protozoon myositis

Trichinosis Cysticercosis Sarcocystosis Hepatozoonosis

Relatively rare. Lesions appear as small poorly defined

pale foci or streaks of necrosis.

These lesions are either infarcts secondary to vasculitis

(blue tongue of sheep) or induced by the direct effect of

the virus (foot& mouth disease virus).

Viral myositis

Affects dog, cat, pigs and man.

Caused by Trichinella spp. (T. spiralis, T. pseudospiralis,

T. nativa and T. nelsoni).

Dead calcified parasites appear as oval nodules in the

form of rows in tongue, masseter, intercostal and laryngeal

muscles.

Grossly

Micro

Focal myositis characterized by the presence of

larvae surrounded by neutrophiles, lymphocytes &

eosinophiles .

Larvae may persist for years or become calcified

Trichinosis

Disease of cattle,sheep, pigs and man.

Caused by C. bovis and C.cellulosa which constitute

the intermediate stage of the tape worm taenia Solium

and taenia Saginata of man and transmitted to man by

Eating unproperly cooked meat.

Cysticerci appear as small white / grey foci in the tongue

masseter muscle and heart .

Grossly

Micro

Myofibers are displaced by the cyst which lies in the

interstitial tissue.

No inflammatory reaction but few lymphocytes, macro-

phages and eosinophiles.

Cysticercosis

Disease of cattle,sheep and pigs caused by sarcocystis

Birds, herbivores reptiles and swine are intermediate

host while carnivores and man are permanent host.

Micro

Muscles of tongue, intercostals and masseters are most

commonly affected

No inflammatory reaction but focal necrosis together

with non suppurative myositis produced by merozoites

after few months of infection

Protozoon disease of dogs & cats caused by the ingestion

of the merozoites of hepatozoon canis and characterized

by pyogranulomatous myositis.

Hepatozoonosis

Sarcocystosis

Protozoon myositis

Bovine and ovine eosinophilic myositis

Disease of cattle and sheep characterized by greenish

discoloration of the muscles mostly those of the back

and thigh.

Micro

a. Myofibers are separated and replaced by extensive eosin-

ophilic cell infiltration followed by lymphocyte and plasma

cells in older lesions.

Degenerated sarcocystis may produce granulomatous

reaction consisting of necrotic muscle surrounded by

macrophages, eosinophiles and fibroblasts.

b.

The cause of EM remains unknown since in most cases Sarcocystis

are directly associated with the lesions and were detected during a

routine postmortem inspection . It is characterized grossly by focal,

green colored muscular lesions.

Skeletal system

Diseases of bone caused either by

Osteopathy

Failure of normal

bone development

Abnormal metabolism

of normal bone

Distortion

Softening

Enlargement

Susceptibility to fracture

Types

Nutritional Toxic Congenital Physical Hormonal

Calcium,phosphorus,vitamin D&A and protein Deficiency.

Starvation.

Under nutrition.

Chronic lead and fluorine poisoning.

Poisonous plants.

Hypervitaminosis D&A.

g

Hypo and hyper secretion of pituitary, parathyroid, thyroid

and gonadic hormones

Genetic inherited factors Traumatic injury of epiphysis of long bones.

Metabolic bone diseases

These are systemic diseases generally of nutritional, toxic

or endocrine origin.

Rickets Osteomalacia Osteoporosis F.osteodystrophy

Young growing

animals

Adults Horses & dogs Adults

(Nutritional) (Nutritional) (Endocrine)

(Toxic)

(Nutritional)

(Toxic)

Rickets Disease of young growing animals caused by failure of

adequate deposition of calcium in bones resulting in bone

deformities and fracture.

Dietary deficiency of calcium.

Causes

Failure of calcium absorption mainly due to :

a.

b.

Formation of insoluble calcium compounds (oxalate,

fatty acids etc.) preventing its absorption from intestine.

Dietary deficiency of Vitamin D.

Increased alkalinity of intestinal contents preventing

its solubility, and its absorption from intestine.

c. Dietary deficiency of phosphorus.

d. High phosphorus in diet.

Pathogenesis

Hypocalcaemia

Grossly

Failure of mineralization of osteoid

and cartilaginous matrix failure of degeneration of

growing cartilage persistence and accumulation of

irregular proliferating cartilage and uncalcified osteoid

tissue Softening of bone.

Enlargement of ends of long bones and costochondral

articulations.

Long bones become distorted and deviated (bow legs).

Flattening of the ends of long bones (due to weight)

causing the margins to lip over the metaphysis giving

it a ( mushroom-like) appearance

Enlarged costo-chondral articulations appear as a string

of beads

Micro

a.

b.

c.

d.

Increased proliferating undegenerated cartilage adjacent

to the metaphysis.

Disarrangement of the proliferating cartilage.

Defective calcification of cartilage & excess uncalcified

osteoid tissue in the metaphysis.

Fibrosis of bone marrow with reduction of myeloid cells.

Bones are soft, easily cut and fractured.

Effect

Lameness due to pain and deformity.

Pathological fracture.

Osteomalacia

Adult rickets

Metabolic disease of adults characterized pathologically

by the accumulation of excess unmineralized, unminera-

lizable osteoid on trabecular surfaces

Causes

Calcium, phosphorus and vitamin D deficiency.

Irregular diffuse thickening of bones which appear

soft, easily cut and deformed.

& clinically by bone

softening, deformity and liability to fracture.

Pathogenesis

Similar to rickets but in a later phase, resorption and

fibrous replacement are common.

Grossly

a.

marrow cavity is enlarged and the cortex is thin and

spongy.

Presence of uncalcified osteoid at the margins of

cortices, haversian canals and bone trabeculae

(osteoid seams)

Active bone resorption with deposition of excess un-

calcified osteoid.

Expansion of haversian canals.

b.

Micro

a.

b.

c.

Hyperparathyroidism

Parathyroid hyperplasia Chronic renal failure High phosphorus diet

A condition characterized by marked bone resorption,

Fibrous osteodystrophy

fibrous replacement, accelerated osteoid formation,

failure of calcification of osteoid tissue & cyst formation.

Cause

Prolonged and excessive action of parathyroid hormone

(hyperparathyroidism).

Parathyroid Neoplasia

Osteodystrophia fibrosa

Primary Nutritional secondary Renal secondary

Primary hyperparathyroidism

Endocrine osteodystrophy Pathogenesis

Parathyroid hyperplasia

Increased output of PTH

Increased osteoclastic activity

Active demineralization of bone

Osteolytic resorption of bone

Increased unmineralized &

unmineralizable osteoid

Softening of bone

fibrous replacement

Grossly

Bones gradually soften, become flexible, deformed and

easily fractured

Multiple areas of rarification and cyst formation.

a.

b.

Micro

a. Marked bone resorption and increased osteoclastic

activity

Fibrous replacement of resorbed bone and bone marrow. b.

c. Thinning of trabecular bone and haversian canals.

Nutritional secondary hyperparathyroidism

Most commonly observed in young growing animals fed on

low calcium, high phosphorus diet (bran fed to horses.).

Bran disease of horses (bighead disease )

A disease of equines mostly horse fed on bran exclusively

characterized by big head and deformity of jaws.

Pathogenesis

Parathyroid hyperplasia

Increased output of PTH

Increased osteoclastic activity

Active demineralization of bone

Osteolytic resorption of bone

Increased unmineralized &

unmineralizable osteoid

Softening of bone & fibrous replacement

Low calcium, high phosphorus diet

Hypo calcaemia & hyper phosphataemia

Grossly

Thickening, softening and rounding of bones particularly

those of the head (upper &lower jaw)

Loosening and loosing of teeth.

a.

b.

big head.

c. Enlarged parathyroid.

Renal secondary hyperparathyroidism

A disease mostly observed in dogs caused by severe chronic

renal diseases, characterized by softening, enlargement and

deformity of bones particularly maxilla and mandible which

become rubbery.

Renal dystrophy-Renal rickets-Rubbery jaw

Grossly

Bones particularly mandible and maxilla become soft,

deformed and rubbery

Pathogenesis

Parathyroid hyperplasia

Increased out put of PTH

Increased osteoclastic activity

Osteolytic resorption and demineralization of bone

Increased unmineralized &

unmineralizable osteoid

Softening of bone & fibrous replacement

Renal insufficiency

Reduced glomerular filtration

Retention of phosphorus

Hyperphosphataemia

Osteoporosis

Osteopenia-Bone atrophy

A condition characterized by decrease density of bone,

it results from an imbalance between bone formation and bone

Resorption (resorption rate exceeds that of formation).

Nutritional

Disuse

Senile Lactational

Hormonal

Toxic

Parasitic

Types

Dietary deficiency of

calcium, phosphorus

following starvation.

Muscular inactivity following long

term paralysis or immobilization of

fractured limb or long recumbency.

Loss of skeletal

mass with aging.

Severe parasitism in sheep Chronic lead and

fluorine poisoning Post menopausal commonly

observed in women

In young gilts fed calcium

phosphorus unbalanced

ration prior to and during

lactation.

Grossly

Osteoporosis mostly affects bones of vertebral bodies,

and metaphysal trabeculae of long bones.

Reduction of bone mass (osteopenia).

a.

b.

c.

a.

d.

Increased porosity of cortical bone and thinning

of trabecular bone.

Bones are brittle and easily fractured.

Trabeculae are reduced in size and number.

Micro

b. Widening of haversian canals and increased porosity

of cortex .

Skin and Appendages

Histopathological Terminology

1- hyperkeratosis It is thickening of the stratum cornium. It may be nucleated (Parakeratosis) or non-nucleated (Orthokeratosis).

2- hypokeratosis

Is a decreased thickening of the stratum cornium.

3- dyskeratosis

Is a premature and faulty keritinization of individual cells. Dyskeratotic cells are esinophilic with swollen cytoplasm and darkly stained nuclei.

The epidermis is the most superficial layer of the skin and provides the first barrier of protection from the invasion of foreign substances into the body. The principal cell of the epidermis is called a keratinocyte. The epidermis is subdivided into five layers or strata, the stratum germinativum (SG), the stratum spinosum(SS), the stratum granulosum(SGR), the stratum lucidum(not seen in this photomicrograph) and the stratum corneum(SC) in which a keratinocyte gradually migates to the surface and is sloughed off in a process called desquamation.

4- Hypergranulosis and hypogranulosis

Indicates an increase or decrease thickening of the stratum granulosum.

5- Acanthosis

Is an increase thickeness f the stratum spinosum. It may be due to hyperplasia (true acanthosis) or due to hypertrophy (peudo acanthosis) of epidermal cells.

6- dysplasia

Is abnormal development of epidermal cells (disorganized formation). It may be precarcinogenic.

7- Spongiosis (intercellular edema)

Is widening of the intercellular spaces of stratum spinosum cells.

8- Intracytoplasmic edema (hydropic degeneration, vacuolar degeneration or ballooning degeneration

Is intracytoplasmic edema followed by rupture of the epidermal cells.

9- Reticular degeneration

Is the bursting of the epidermal cells by severe intradermal edema with formation of multilocular intraepidermal vesicles.

10- Microvesicle and vesicle

Are microscopic and macroscopic intraepidermal and/or subepidermal fluied –filled cavities. It results from intracellular or intercellular edema.

11- Acantholysis ( dyshesion, desmolysis, desmorrhexis)

Is a loss of cohesion between epidermal cells resulting in intraepidermal clefts, vesicles and bullae).

12- Bulla

Is a large inter or subepidermal cavity results from the coalescence of many vesicles.

13- Acne

Is a suppurative inflammation of the hair follicles or sebaceous gland.

14- Microabscesses and pustules

Are microscopic and macroscopic intraepidermal and/or subepidermal vesicles filled with pus.

15- folliculitis (pyoderma)

Is a severe form of suppurative inflammation of hair follicle and dermis characterized by necrosis of the deep parts of the hair follicle which are filled with pus and surrounded by severe inflammatory reaction, thickened, indurated and alopecic areas of the skin with ulceration of the overlying epidermis.

16- furunculosis

Is a an abscess in the deep dermis which rupture through the epidermis leaving a hole in the epidermis and a canal leading down into the dermis.

17- Carbuncle

Is a deep dermal abscess which opens through many sinus tracts.

18- Exocytosis

Is the margenation of the inflammatory cells and/or erythrocytes through the intercellular spaces of the epidermis..

19- Pachyderma

Is a focal thickening of the skin involving all the skin layers.

20- Erosion (Excoriation)

Is a superficial loss of epidermal or epithelial cells

Is the loss of the epidermis with exposure of the underlying dermis..

21- ulcer

22- Fissure

Is a linear defect in the epidermis..

23- Erythema

Is a circumscribed area of edema and congestion of the papillary dermis.

24- Albinism

Is a generalized congenital lack of melanin pigment throughout the entire body due to lack of tyrosinase enzyme necessary for melanin synthesis.

25- Vitiligo

Is an aquired loss of melanin pigmnet in a focal areas of skin (burns or scars).

26- Acanthosis nigricans

Is a condition commonly observed in man and dogs characterized by patches of heavily pigmented rough thick skin ( acnthosis and hyperpigmentation with melanin).

27- Keloid

Is a hypertrophic scar characterized by heavy bundles of esinophilic collagen in the dermis, elevated epidermis which may become ulcerated

28- Crust Is a consolidated, desiccated surface mass composed of varying

combinations of keratin, serum, cellular debris and few microorganisms.

29- Xanthomatosis

Is a nodular accumulation of large epitheloid cells (laden with lipid substance) and multinucleated giant cells in the dermis and subcutis (in association with disturbance of lipid metabolism).

30- Congenital icthyosis

Is a condition of newborn calves characterized by thick, scaly, horny hairless skin which resembles skin of fish.

Dermatitis

Inflammation of the skin which may be

* acute

*subacute

*chronic

* focal

*diffuse

*Serus *Serohemorrhagic *Suppurative *granulomatous

*spongiosis

*Intercellular edema

*Leukocytic

infiltaration

*Vascular dilatation

*Perivascular cell

infiltartion

*similar to acute form

+

The reaction is

proliferative and

Infiltrative

+

Fibroplasia

Mononuclear cell

infiltration

*similar to acute from

+

•Epidermal hyperplasia.

•Ortho or parakeratotic

hyperkeratosis.

Acute form

characterized by

Chronic form

characterized by

Subacute form

characterized by

Generally the microscopic picture varies with the type of exudates and the nature of infection and causative agent.