Exam 3 Flashcards
2 Types of Bone Formation
Endochondral
• bone formation on a cartilage template
• Ex: growth plate or fracture repair
Intramembranous
• formation from a loose fibrous framework
Requirements for complete repair of bone
- Limited motion
- Adequate vascularity
- Sterility
- Apposition
- Adequate host nutritional status
Secondary Lesions in Bone
- “reactive” new bone (infection, neoplasia)
- microfractures, compression fractures (physes)
- hemorrhages (physes)
3 Techniques for Examination of Bone
Imaging
• radiography & MRI
Biopsy
• avoid reactive new bone
• sample multiple sites
• Best practice: submit radiograph with biopsy
• diagram lesion to show biopsy site(s)
• Amputation: consider submission of entire limb
• Very thin sample
• demineralization is required to section bone
• prolongs turn-around time
Necropsy
Basics of Secondary Bone Healing
o Transforms unstable fracture into rigid bone
o no rigid fixation -> motion stimulates callus (granulation tissue) -> stabilizes & provides extraosseus blood supply
o inflammation -> repair -> remodeling
Inflammatory Phase of 2nd Bone Healing
Tissue damage & hemorrhage
• clot formation
• disruption of blood supply
• ischemic necrosis of bone
Inflammation
• Increase vascular permeability
• emigration of phagocytes
• new blood supply (extraosseous)
Granulation tissue
• Fibroblasts
• Neovascularization
Repair Phase of 2nd Bone Healing
Pluripotent mesenchymal cells unite fracture fragments
• Osteoblasts, chondroblasts, fibroblasts
• Increased O2 due to blood supply
Cells & matrix form callus
• Periosteal & endosteal
• Excessive motion = problem -> decrease O2 & increase callus size
Increased osteogenesis
• Cartilage & necrotic bone replace w/ new bone = endochondral ossification
Hard callus
• Strong enough for support but not max strength
Remodeling Phase of 2nd Bone Healing
Osteoclastic resorption
• Replaces woven bone w/ cortical bone
Re-establish normal blood supply
• Resorption of endosteal callus
• Resorption of periosteal callus & loss of extraosseus blood supply
Primary Bone Healing; requirements, 2 subtypes
o no callus formation
Requirements
• Adequate blood supply
• Rigid immobilization
(most important)
• Excellent reduction and anatomic alignment
Subtypes
• Contact
• Gap
Osteomyelitis; what is it? clinical signs?
o Inflammation of the bone
o Usually caused by infection
Clinical Symptoms • Lameness • Paresis • Draining tracts • Fever
Osteomyelitis; tissue response, sequestrum
Tissue Response
• Necrosis of bone (osteolysis) & inflammatory exudate
• Removal of dead bone (resoprtion)
• Production of new bone (regeneration)
Sequestrum • Necrotic bone = no blood supply • Surrounded by exudate & involucrum • Resorption can’t occur • May drain via tracts and dissolve (if small) • Surgical removal usually required
Osteomyelitis Sequestra in horses
- Non-healing draining lesion
- May drain distant to primary site
- Usually no lameness
Treat
• Surgical excision
• Antibiotics usually don’t work due to decreased blood supply
Causes of Osteomyelitis
- Trauma
- Direct extension from infected site
Hematogenous
• Often multifocal
• Bacteremia
Specific Organisms
• Aerobic or anaerobic bacteria
• Fungi
Vertebral Osteomyelitis
o Causes posterior paresis in pigs
Paresis due to:
• Pathologic fracture
• Myelomalacia
• myelitis
Nutritional Bone Dz; Common lesions & nutritional components
Common Lesions
• Osteopenia (bone loss)
• Bone deformities
• Pathologic fractures
Common Nutritional Components • Common in exotics • Fad diets • Economic stress • Mixing errors
Basics of Metabolic Bone Dz
o Failure of bone production, mineralization, and/or maintenance
o Osteodystrophy = defective bone formation
o Occurs in young during formation or adults during remodeling
o Forms of metabolic bone Dz overlap
o Nutritional deficiencies are often cause but ratio more important than overall level
Forms of Metabolic Bone Dz
Osteomalacia
• decreased mineralization of osteoid in adults
Osteoporosis
• decreased amount of normal bone
Rickets
• Decresed mineralization of osteoid & cartilage during growth
Fibrous osteodystrophy
• Osteoporosis or osteomalacia + intertrabecular fibrosis
• Due to increased PTH
Osteoporosis; basics, causes, examples of causes
- pathologic reduction in bone mass (adults)
- cortical bone is reduced in thickness & increased in porosity
- potentially reversible
- localized or generalized
causes:
• excessive rate of bone removal
• subnormal production of new bone
Examples
• Disuse
• Starvation
• Ca deficiency
Osteomalacia; pathogenesis, lesions, compensation, causes, clinical signs
• defective mineralization of osteoid (adults)
pathogenesis:
• part of the normal remodeling process, aged, well-mineralized bone is removed ->
• replaced by osteoid that is inadequately mineralized.
lesions
• unmineralized osteoid matrix + active resorption
Compensation:
• excessive deposition of osteoid matrix at places where the mechanical forces are strongest.
Causes
• Vit D deficiency
• Phosphorus deficiency
Clinical Signs
• Soft bones
• Pathologic fractures
• Deformities
Rickets; causes, clinical signs
- Juvenile form of osteomalacia
- Inadequate mineralization of osteoid & cartilage
Causes
• Vit D deficiency
• Phosphorus deficiency
Clinical Signs
• Lameness
• Enlarged metaphyses
• Pathologic fractures
Rickets pathogenesis
- Failure of mineralization of cartilage ->
- Failure of degeneration of chondrocyte columns ->
- Formation of osteoid ->
- Overgrowth of fibrous tissue in the metaphysis ->
- Deformities in the shape & structure of bone ->
- enlargement of joints of limbs ->
- microfractures, microhemorrhage, repair, etc
Fibrous Osteodystrophy; pathogenesis & clinical signs
Pathogenesis
• Hyperparathyroidism (increased PTH) ->
• Increase osteocalstic resorption of bone ->
• Osteoporosis or osteomalacia ->
• Excessive fibrous CT btwn remaining trabeculae
Clinical Signs
• Lameness
• Pathologic fractures
• Rubber jaw, enlarged head
Two Causes/paths of Secondary Hyperparathyroidism
Dietary imbalance in Ca/P • Hyperphosphatemia -> • Hypocalcemia –> • Increased PTH -> • Fibrous osteodystrophy
Chronic Renal Dz • Decreased ability to excrete phosphate -> • Hyperphosphatemia -> • Decreased ability to resorb Ca -> • Functional hypocalcemia -> • Decreased ability to hydroxylate Vit D -> • Decreased ability to catabolize PTH -> • Fibrous osteodystrophy
Primary Vs Psuedo Hyperparathyroidism
Primary
• Uncommon
• Caused by functional PTH tumors
• Clinical signs due to hypercalcemia
Signs
o PU/PD, vomit, weakness, metastatic calcification
o Fractures +/- facial hyperostosis
Pseudohyperparathyroidism
• common
• paraneoplastic syndrome
• hypercalcemia induced by “pth-like” factor
• mild bone atrophy
• clinical signs are due to hypercalcemia
Tumors o lymphoma (dogs), o adenocarcinoma of anal sacs (dogs)
Chondrodysplasia; basics & example
- Defective cartilage formation
- inherited
- unequal growth across physis
- endochondral ossification
- irregular, haphazard columns of chondrocytes
- EX: snorter calves (short & smushed face)
Angular Limb Deformities; basics & common types in horses, llamas, dogs
- Medial or lateral deviation of distal limb
- Unequal growth across physis
- Treat w/ osteoectomy
Foal:
• carpus valgus - incomplete ossification of carpal and tarsal bones
Llamas:
• Deviation typically centered on distal radius & ulna
Dogs:
• radius curvus - premature closure of the physis at the distal ulna
6 Bone Tumors
Osteosarcoma
• Common & important
Other primary neoplasias
• Fibrosarcoma
• hemangiosarcoma
Metasttic tumors
Chondrosarcoma
• 2nd most common
benign tumors of bone
• uncommon
Osteosarcoma Basics
- mesenchymal tumor
- produces osteoid and/or bone
- > 80% of primary bone tumors in dogs & cats
- common in large heavy dogs
- Dogs (7.5 yr), Cats: (10.5 yr)
- Metaphysis of long bone (usually forelimb in dogs)
- Presents w/ lameness +/- swelling
- Radiographs to diagnose
- Dogs > cats > horses/cows
Osteosarcoma Behavior & Survival
Behavior
• Aggressive local invasion (osteolytic)
• destroys cortical bone
• rarely crosses joints
• undermines the periosteum and stimulates reactive new bone
• Micrometastasis
• Early pulmonary metastasis
Survival
• w/ surgery & chemo > w/ surgery > w/o surgery
Osteosarcoma in the Axial Skeleton
- Uncommon
- Most common site is maxilla
- May have longer survival rate than appendicular
Secondary Bone Tumors; symptoms & 3 mechanisms
Symptoms
• pain - pathologic fracture
• +/- hypercalcemia
• osteolysis +/- new bone formation
3 mechanisms
• Bone marrow - plasma cell myeloma vertebral lesions
• Local invasion - Oral SCCa -> mandible Nasal adenoCA -> skull
• Metastasis - K9 prostatic and transitional cell Ca
Chondrosarcoma; basics & behavior
- Malignant mesenchymal tumor that produces cartilage
- Dogs & sheep
Behavior
• flat bones = ribs, nasal cavity, skull
• most arise in medullary cavity
• may destroy existing bone (osteolysis)
• develop slower, metastasizes later, can get very large w/o signs, better prognosis
Intervertebral Disks
Nucleus Pulposus • Center of disc • gelatinous, avascular • 85% water • shock absorber
Annulus Fibrosus • thick, fibrous membrane • thickest ventrally • outer fibers blend with dorsal & ventral spinal ligaments • provide strength
Intercapital Ligaments
o collagenous cord head of rib -> dorsal aspect of disc -> head of oppposite rib.
o stabilize ribs
o adds strength to annulus fibrosus
o No intercapital ligament for first pair or last two pairs of ribs.
o ligament for 11th pair of ribs is smaller
Pathogenesis of IVDD
- loss of H20 and proteoglycans in nucleus pulposus ->
- reduced cellularity ->
- increased collagen = decreased compressibility ->
- loss of distinction between annulus fibrosus & nucleus pulposus ->
- central portion of nucleus -> fibrocartilage ->
- chondrometaplasia +/- mineralization ->
- weakened annulus ->
- dorsal herniation of altered nucleus pulposus ->
- degeneration & rupture of annulus fibrosus ->
- extrusion of disk material into spinal canal ->
- compression of spinal cord
Chondrodystrophic Breeds Vs Non in IVDD
Chondrodystrophic • EX: Dachshund • Accelerated process • Chondroid metaplasia w/in 1st year of life • Calcification of disc is common
Non- Chondrodystrophic
• Degeneration later in life
• Mineralization is uncommon
• Only partial rupuyre of annulus w/ dorsal bulge of disc
Common Sites Herniated Disks
- T11 – L3 (mostly)
- Cervical
- Where there is not intercapital ligaments
Classification of Herniated Disks
Type I
• Most common
• Complete prolapse of disc +/- explosion (extrusion)
• Unilateral signs
Type II
• Partial rupture/buldging (protrusion)
• More usual in non-chondrodystrophic breeds
IVDD; Symptoms, Diagnosis, Treatment
Symptoms
• Ischemic myelopathy = neuro signs
• Pain (most common)
Diagnosis
• Signalment, history, neuro exam
• Imaging: rads, myelogram, MRI
Treatment
• Corticosteroids + confinement
• Surgery: dorsal laminectomy or hemilaminectomy
Cervical vertebral malformation-malarticulation; Basics & Causes
o Cervical spinal atrophy due to stenosis of vertebral column
o Wobblers
o Static or dynamic (happens w/ movement)
Causes • Congenital • Developmental • Osteoarthritis • Nutritional • Combo
Wobblers in Horses; clinical signs & Lesions
• Myelomalacia = focal compression of spinal cord
Clinical signs • ataxia “wobbles” • general proprioceptive deficits • more apparent in the hind limb • before 3YO • thoroughbreds
Lesions
• Stenosis
• Vertebral column subluxation
• Secondary osteoarthritis
Wobblers in Dogs; True malformation Vs Secondary Change
- Cervical spondylomyelopathy
- Static or dynamic
True malformation
• Stenotic lesion
• Rounding of Cranioventral vertebrae
• EX: young great danes
Secondary Change • Disk associated • Middle age/old Dobermans • Thickening of dorsal annulus fibrosus -> • Ventral compression of cord
Spondylosis; basics, signs in dogs Vs cows & sheep
o Proliferative spurs of bones (osteophytes)
o Develop at ventral & lateral aspects of vertebral bodies
o Bridge to adjacent vertebrae
Dogs
• Common in old dogs
• Often asymptomatic
• May have stiffness, decreased motion, pain
• If severe AND extending dorsolaterally -> impinge nerve roots
Cows & Sheep • Bulls & rams • Breeding males • Slowly progressive • Usually subclinical • Clinical signs following bridging fracture: stiff, reluctance to mount, CNS signs
Vertebral Osteomyelitis; basics, symptoms
o Hematogenous
o Bacterial caused
o Localized in epiphysis
Symptoms
• Paresis/paralysis
• Spinal cord compression
• Myelitis
Diskospondylitis
o Infection of intervertebral disc w/ osteomyelitis of contiguous vertebrae
o Hematogenous
o Bacterial caused
Articular Cartilage Response to Injury; superficial, deep, progressive
o Limited regeneration
o Damage can’t be seen on rads but healing may be
Superficial
• No healing
• No worsening
Deep
• May heal w/ fibrovascular tissue -> fibrocartilage
Progressive Damage
• Loss of proteoglycans + tearing of collagen fibers ->
• Fibrillation (dull, rough, yellow brown cartilage) ->
• Exposure of subchondral bone ->
• Eburnation (dense, polished, ivory like)
Repair Cartilage in Place of Articular Cartilage
o fibrous (fibrocartilage) o hypercellular o Type I collagen predominates o diminished glycosaminoglycans o inferior substitute
Synovial Membrane Response to Injury; acute, chronic, what is pannus
Acute
o hypertrophy & hyperplasia of synovial cells -> proliferative synovitis
o may have villous hypertrophy
Chronic • Granulation tissue arises at synovial membrane -> articular surface = pannus • May dmage underlying cartilage • May progress to ankylosis • Produces catabolic factors
Pannus:
• cloth like
• invasive granulation tissue
• releases collagenolytic enzymes
Periarticular (perichondral) Bone Response to Injury
o Cartilagenous nodules ->
o Converted to bone via endochondral ossification =
o Periarticular osteophytes
Synovial Fluid Response to Injury
o Increased quantity of fluid o Inflammatory cells o Fibrin & immunoglobulin o Synovial cells o Change in viscosity
Osteoarthritis; basics & pathogenesis
o Progressive deterioration & loss of articular cartilage
o Eventually leads to eburnation & osteophytes
Pathogenesis
• Decreased matrix macromolecules ->
• Increased metalloenzymes ->
• Degredation of proteoglycans & collagen ->
• Changes in mechanical properties of cartilage ->
• More damge -> more destruction (cycle)
Osteoarthritis; Treatment & Causes
Treatment • Weight control • Anti-inflammatory & pain management • Exercise • Chondroprotective agent
Causes • Trauma to articular cartilage • Abnormalities in conformation • Joint instability • Joint incongruence • Lubrication failure
Osteochondrosis; basics & pathogenesis
o Dyschondroplasia
o focal or multifocal areas of failure of endochondral ossification in epiphyseal
(and/or physeal) growth cartilage
o young, rapidly growing animals
o multiple joints usually affected
o particular joints characteristic for particular species
Pathogenesis
• hypertrophic zone of cartilage cells focally retained & calcification of matrix FAILS
->
• Capillaries do not invade abnormal matrix ->
• no endochondral ossification ->
• focus of retained, thickened cartilage ->
• Site of weakness
Osteochondrosis; lesions, symptoms
Lesions
Thickening of cartilage in epiphysis
• limits nutrient diffusion = necrosis of deeper layer
Osteochondritis dissecans =
• cartilage sparation -> flap stimulates inflammation -> inflammation inhibits fibrocartilage
Subchondral Cysts
• Cartilage damage weakens underlying bone -> cyst formation
• mostly in HORSES
• Radiograph: focal area of radiolucency in the epiphysis
Symptoms
• Lameness / pain
• Can progress to chronic osteoarthritis
Neonatal Septicemia & Polyarthritis; baics, route, symptoms
- Serofibrinous joint fluid
- High number neutrophils on cytology
- Can progress to destruction of cartilage
- Usually irreversible damage
- Hematogenous Route
Symptoms
• Swollen, hot, painful joints
• Febrile
Non-Infectious Arthritis (Erosive/Deforming)
- Ex: Rheumatoid
- Dogs most common
- Immune mediated destruction & ankylosis of joints
- Soft tissue swelling -> erosion -> destruction of cartilage & bone
Diagnosing Rheumatoid
• Rheumatoid factor is auto-Ab against FC portion of IgG
Systemic Lupus Erythematosus; basics, symptoms, diagnosis
- Non-erosive non-deforming non-infectious arthritis
- Multisystemic auto-immuned Dz
- Circulating immune complexes and/or Abs against blood cells
Symptoms
o No single clinical sign
o IMHA, thrombocytopenia, leukopenia, glomerulonephritis
o polymyositis, polyarthritis, polyarthralgia, dermatitis
o shifting leg lameness, recurrent fever
o minimal villous hypertrophy, no destructive pannus
o NO irreversible damage to cartilage
Diagnosis
o ANA – Ab to DNA or nucleoproteins
o Not very sensitive
Immune Complex Deposition in joints; basics, 2 causes, symptoms
• Non-erosive non-deforming non-infectious arthritis
Drug Hypersensitivity
o Deposition of drug-Ab complexes (antibiotics)
Secondary to infectious dz
o Antigenemia or bacteremia
o Circulating immune complexes
o Reactive polyarthritis
Symptoms • fever • glomerulonephritis • anemia • thrombocytopenia • lymphadenopathy • polyarthritis (non-erosive)
Reactive Polyarthritis, symptoms, rads, arthrocentesis, treatment
• Reaction to drug or infection
Symptoms
• Polyarticular lameness
• Fever
• No antibiotic response
Radiographs
• Lack of bony change
Arthrocentesis
• Sterile
• Increased neutrophils
Treatment
• Remove drug
• Resolve infection
How is the endocrine system regulated
o Negative feedback is primary control mechanism
o Hierarchical levels of regulation
o Cross communication btwn endocrine organs
Primary Vs Secondary Endocrine Dz
Primary Disease
• originates w/in the endocrine gland
Secondary Disease:
• originates outside of the gland
• inflammation in one organ can cause damage to a neighboring endocrine gland
Disease due to excess hormone activity (4 categories)
Primary:
• usually due to functional neoplasia of endocrine tissue (with unregulated hypersecretion of hormone)
Secondary:
• Excess stimulation of the gland
• Inadequate inhibition (loss of negative feedback) on the gland
• Inadequate degradation/excretion of the hormone
Iatrogenic:
• exogenous source of a hormone (steroid therapy)
Non-endocrine neoplasia (paraneoplastic syndrome):
• some neoplasias secrete hormone homologs with hormonal activity
Disease due to inadequate hormone activity (3 categories)
Primary:
• usually auto-immune damage to the gland
Secondary:
• Inadequate stimulation
• Inadequate nutrition necessary for hormonal production
• decreased target cell receptors/response
• increased degradation/excretion of the hormone
Iatrogenic:
• surgical or medical destruction or inhibition of the gland
Atrophy Vs Hypoplasia
Atrophy
o After development
o Caused by chronic inflammatory or chemical destruction (irreversible) and lack of hormonal stimulation (reversible)
Hypoplasia
o Before organ maturity
o Caused by inadequate organ development (irreversible)
Neoplasia of Endocrine; basics, 4 types
- irreversible unregulated proliferation of abnormal cells
- may or may not be functional
adenoma:
o benign
microadenoma
o NOT grossly visible
macroadenoma
o grossly visible mass
adenocarcinoma
o malignant
Diseases of the Adenohypophysis of the pituitary
Hypopituitarism:
• deficient pituitary hormonal activity
Hyperpituitarism:
• excess pituitary hormonal activity
Hypopituitarism; causes, pathogenesis, clinical signs
Causes
o Non-functional neoplasms can leading to deficient production of hormones (adenoma most common)
o Inflammation/infection (Pituitary abscess ruminants)
o Pituitary cysts (cause dwarfism)
Pathogenesis
o Mass effect or destruction of tissue
o Loss of functional pituitary & compression of adjacent structures
Clinical Signs
o Peripheral endocrine gland atrophy due to lack of hormonal stimulation
o Reduced antidiuretic hormone (ADH) production and secretion
o Blindness (compression upon the optic chiasm)
o +/- CNS signs
Hyperpituitarism; usual cause, example diseases
- Often caused by neoplasia
- Pituitary pars intermedia dysfunction (Equine)
- Pituitary-origin canine Cushing’s syndrome
Pituitary pars intermedia dysfunction; species & pathogenesis
o Affects 81% of horses > 15YO
Pathogenesis
• Gradually decreased hypothalamic dopamine ->
• reduced inhibition of some hypothalamic hormone production ->
• hyperstimulation ->
• functional pituitary adenoma of the pars intermedia (slow growing macroadenoma)
Pituitary pars intermedia dysfunction Clinical Signs
• Due to compression of hypothalamus
4H’s
• hairy, hyperhidrosis, hungry, heavy
Hirsutism
• Hypertrichosis (hairy) due to lack of seasonal shedding cycles
Hyperhidrosis
• excessive sweating due to hirsutism and loss of body temperature control
Polyuria/polydipsia
• due to reduced antidiuretic hormone secretion
Somnolence
• Sleepiness due to loss of hypothalamic control of sleep patterns
Polyphagia
• overeating due to damage to the hypothalamic appetite center
Laminitis
• Idiopathic
Pituitary-origin canine Cushing’s syndrome Primary & Secondary Lesions
Primary Lesion
• ACTH-secreting pars distalis adenoma (most common)
• Microadenoma more common than macro
Secondary Lesion
• Bilateral adrenocortical hyperplasia
Diseases of Neurohypophysis of the pituitary
diabetes insipidus
- Neurogenic
- Nephrogenic
Diabetes Insipidus Neurogenic; Pathogenesis & Clinical Signs
Pathogenesis
• Neoplasia, Inflammation/Infection, or Pituitary Cysts ->
• destruction of neurohypophysis or hypothalamus ->
• loss of ADH synthesis OR loss of ADH transport/release
Clinical Signs
• Polydipsia & Polyuria
Hyperadrenocorticism Clinical Signs
• All forms have same clinical signs but different underlying causes
Clinical Signs • Prolonged elevated cortisol -> excessive/chronic stress response • Polyphagia • Hepatomegaly due to excessive glycogen storage • Skin changes • Muscle wasting & weakness and lethargy • Pendulous abdomen • Immunosuppression • Hypertension • hypercoagulability • Hyperlipemia / Hypercholesterolemia • PU/PD • Hyperglycemia (variable)
Pituitary-dependent hyperadrenocorticism; primary & secondary lesions, pathogenesis
• Most common form of canine hyperadrenocorticism
Primary lesion:
o Functional pituitary adenoma
Secondary endocrine lesion:
o Bilateral adrenocortical hypertrophy
Pathogenesis of secondary lesions: o Functional pituitary adenoma -> o unregulated hypersecretion of ACTH -> o bilateral hyperplasia of zona fasciculata -> o hypersecretion of cortisol
Adrenal-based hyperadrenocorticism; primary & secondary lesions, pathogenesis
Primary lesion:
o Functional adrenal cortical neoplasm: usually adenoma, rarely carcinoma
Secondary lesion:
o Contralateral adrenocortical atrophy
Pathogenesis of secondary lesions:
o Functional adrenal cortical neoplasm ->
o unregulated hypersecretion of cortisol ->
o suppression of pituitary ACTH secretion ->
o contralateral adrenocortical atrophy
Iatrogenic Hyperadrenocorticism; primary & secondary lesions, pathogenesis
• very common
Primary cause:
o Excessive use of exogenous corticosteroids
Secondary lesion:
o Bilateral adrenal cortical atrophy
Pathogenesis of secondary lesions:
o Prolonged excessive exogenous corticosteroid administration ->
o (-) feedback on the hypothalamic-pituitary-adrenal axis ->
o suppressing pituitary ACTH secretion ->
o affects both adrenals.
Hyperadrenocorticism in ferrets (adrenal associated endocrinopathy); signalment, primary lesions, pathophysiology, clinical signs
Signalment:
o Females > males
o Adults, usually fixed
Primary Lesion:
o Unilateral adrenocortical adenoma/adenocarcinoma
o Bilateral hyperplasia
Pathophysiology:
o Increased production of adrenocortical estrogenic steroids ->
o hyperestrogenism
Clinical signs:
o bilaterally symmetric alopecia
o Vulvar enlargement (common)
o Pyometra/endometrial hyperplasia (common)
o Anemia/thrombocytopenia (common) due to bone marrow suppression
o Polyuria/polydipsia (uncommon)
Typical Addison’s Disease; primary lesion & two precursors to pathophysiology
Primary Lesion
o Adrenal cortical atrophy/necrosis
Pathophysiology
o Idiopathic
o Iatrogenic
Iatrogenic Pathophysiologies of Typical Addison’s
Adrenalectomy ->
• rapid loss of 50% of total functional adrenal cortex ->
• transient Addison’s disease ->
• contralateral gland develops compensatory hyperplasia.
Cytoxic drug overdose ->
• rapid & selective destruction of adrenal cortex ->
• bilateral loss of functional cortex. ->
• Irreversible if sufficient loss.
Receptor inhibition therapy (e.g. Trilostane) for Cushing’s
Reduced Functional Mass of Zona Glomerulosa Vs Zona Fasciculata
Zona Glomerulosa
• Decreased K+ excretion = Hyperkalemia
• Decreased Na retention = hyponatremia
Zona Fasciculata
• Deficient cortisol
• Vomiting, diarrhea, anorexia, weight loss
Clinical Signs of Typical Addison’s
Can be episodic & variable
o GI signs
o Muscle weakness, arrhythmias, bradycardia
o PU/PD
o Hypotension, renal insufficiency/failure
o hypoglycemia
o No response to exogenous ACTH
Atypical Addison’s Disease; primary lesion, pathophysiology, clinical signs
Primary lesion:
o Atrophy of the adrenal zona fasciculata, ONLY
Pathophysiology
o Reduced functional mass of zona fasciculata ->
o deficient cortisol but NOT deficient aldosterone ->
o signs related to low cortisol.
Clincal Signs
o GI signs
o PU/PD
o Hypoglycemia
Atypical Addison’s Disease;; 3 Pathogenesis
Iatrogenic:
• Long-term usage of corticosteroids ->
• inhibition of CRH & ACTH release ->
• reversible atrophy of the zona fasciculata.
Idiopathic:
• May progress to typical (full) Addison’s disease
• irreversible
Pituitary insufficiency
• congenital panhypopituitarism (rare)
2 Types Hyperplasia of the adrenal cortex
Nodular cortical hyperplasia (unilateral or bilateral):
• Usually z. glomerulosa or z. fasciculata
• Very common in adult animals
• clinically insignificant.
• Looks normal grossly
Diffuse and bilateral cortical hyperplasia:
• Usually due to hypersecretion of ACTH by a functional pituitary neoplasm
2 Neoplasia of Adrenal Cortex
Adrenal cortical adenoma
• Usually functional causing hyperadrenocorticism
• Can look like nodular cortical hyperplasia
• Should be encapsulated
• Will commonly be larger than nodular hyperplasia
Adrenal cortical carcinoma
• May be functional in dogs, but usually not
• Locally invasive
• Can invade caudal vena cava causing hemoabdomen
• May be bilateral
• Can metastasize
Neoplasia of Adrenal Medulla, basics & clinical signs
• Pheochromocytoma
most common
• cattle and dogs (commonly malignant in dogs)
• can look like adrenal cortical neoplasms
• usually unilateral areas of necrosis
• often invasive & metastatic
• most are nonfunctional
• can have sporadic release of (nor)epinephrine:
Clinical Signs (of functional)
• paroxysmal (episodic) hypertension & tachycardia
• periodic panting, tachypnea, and collapse +/- GI signs
• ventricular hypertrophy
Diabetes Mellitus clinical signs & pathophysiology
Clinical Signs • Persistent hyperglycemia postprandial & fasting • PU/PD • Polyphagia w/ weight loss • Cystitis • Bilateral cateracts
Pathophysiology • Low insulin secretion or activity -> • Decreased cellular glucose uptake -> • Persistent hyperglycemia -> • Glucagon secretion -> • Paradoxical mobilization of energy sources -> • Hepatic lipidosis & weight loss
What happens if Diabetes Mellitus is left untreated
- Ketoacidosis & ketonuria ->
- Osmotic polyuria ->
- Shock & acidosis ->
- Osmotic cellular dehydration ->
- Diabetic coma
Primary Diabetes Mellitus (Type I); basics, lesions, pathogenesis
o Defect in insulin system
o Insulin dependent
o Most common form in dogs
Primary Lesions
• Autoimmune isletitis
• Congenital deficiency
Pathogenesis • Damage to Beta cells -> • Deficient insulin levels OR • Congenital deficiency of beta cells & islets -> • Deficient insulin levels
Primary Diabetes Mellitus (Type II); basics, lesions, pathogenesis
o Non-insulin dependent
o Most common form in cats
Lesions
• Not always present
• Can have islet (beta cell) vacuolation & amyloidosis
Pathogenesis
• Chronic glucose/lipid toxicity (obesity) ->
• Insulin resistance ->
• Deficient insulin activity ->
• Pre-diabetes & increased insulin demand ->
• Mild dysregulation of blood glucose ->
• Beta cell exhaustion ->
• Deficient insulin secretion & resistance
Secondary diabetes Mellitus; basics, two causes
• Defect in other system that affects insulin
Secondary loss of beta cells due to
o Infiltrative neoplasia into islets
o Chronic relapsing pancreatitis
Secondary inhibition of insulin activity due to
o Insulin receptor antagonism by hormones
o Hypercortisolism
o Acromegaly & growth hormone
Excess Insulin; species, causes, clinical signs
• Ferrets > dogs»_space;> cats
Cause
• Functional pancreatic beta cell neoplasm
• Ferrets: Beta cell adenoma (insulinoma)
• Dogs: beta cell carcinoma (malignant insulinoma)
Clinical Signs
• Episodic hypoglycemia due to sporadic insulin release
• Weakness & lethargy
• Collapse, seizures, obtunded
Typical Addison’s Disease; deficiencies and results thereof
Deficient cortisol • Leukocytosis • Neutrophelia • Eosinophilia • Hypocholesterolemia • Hyponatremia
Deficient ALD
• Hyponatremia
• Hyperkalemia
Pituitary Pars Intermedia Dysfunction (PPID); basics, species, clinical signs
• Hypothalamus dysfunction of equine
Clinical Signs • 3 Hs • hirsutism (hairy) • hyperhidrosis (sweaty) • polyphagia (hungry) • somnolence (sleepy)
Thyroid Basic Structure & Function
Follicular cells
• produce T3 & T4
Parafollicular cells (C cells)
• produce calcitonin
• prevent hypercalcemia
• increase renal clearance of Ca & P
T3
• increases metabolic rate
TSH
• Stimulates follicular cell hyperplasia
• Thyroid hormone production requires iodine
Hypothyroidism in Dogs; age, gross/histo lesions & clinical signs
• Middle aged
Grossly
• Small atrophied thyroid
Histo
• Lymphocytic thyroiditis – autoimmune (most common)
OR
• Idiopathic follicular atrophy
Clinical signs • Fat • Five • Flaky • Furless • Weight gain w/o polyphagia • Nonregenerative anemia • Lethargy & weakness • Hyperlipidemia/cholesterolemia • Neuromuscular symptoms
Hypothyroidism in Grazers; age, lesions & causes
• Fetuses or neonates = congenital
Grossly
• Large thyroid = goiter
• Diffuse follicular hyperplasia
Causes
• Iodine deficiency
• Iodine toxicity inhibits hormone synthesis
• Goitrogenis plants inhibit hormone synthesis
Hyperthryroidism; species, lesions, clinical signs
• Common in cats
Primary Lesions
• Nodular/multinodular hyperplasia of thyroid
• Large thyroid
Clinical Signs
• Weight loss w/ polyphagia
• Hyperactivity
• Tachycardia/arrrhytmias
Neoplasias of the thyroid
Thyroid follicular adenoma
o Unilateral w/ contralateral atrophy
o Causes hyperthyroidism
Follicular carcinoma
o Usually not function
o Dogs > cats
Function & cells of the parathyroid gland
Chief cells
• Produce PTH
• Prevent hypocalcemia
Hypoparathyroidism; species, causes, clinical signs
• Dogs
Causes • Parathyroiditis • Neoplasia • Thyroidectomy • Atrophy due to high Ca diet & sudden removal of Ca
Clinical Signs
• Persistent hypocalcemia
• Muscle spasms and weakness
Main Clinical Finding of Hyperparathyroidism
- Fibrous osteodystrophy
* Osteoporosis or Osteomalacia PLUS Intertrabecular Fibrosis
Four types of Hyperparathyroidism; causes & relation to Ca
Primary
• Associated w/ hypercalcemia
• Unregulated PTH -> hypercalcemia
• Caused by functional chief cell neoplasia
Psuedo
• Associated w/ hypercalcemia
• Caused by non chief cell neoplasia (paraneoplastic)
Renal Secondary • Associated w/ normal to hypocalcemia • Chronic renal failure -> • inability to activate vit D -> • chronic increase in PTH -> • Bilateral chief cell hyperplasia
Nutritional Secondary • Associated w/ normal to hypocalcemia • Improper Ca/P ratio +/- vit D deficiency -> • Chronic increase in PTH -> • Bilateral chief cell hyperplasia
Clinical signs of primary & pseudo Hyperparathyroidism
- Mild/absent signs
- Bradycardia
- PU/PD
- Urinary calculi
- Metastatic mineralization
Define: erythema, indurated, lichenification, uticaria, macule
Erythema
o Redness of the skin due to capillary congestion
Indurated
o Hardened
Lichenification
o Thickening of skin
Uticaria
o Transient hives
Macule
o circumscribed spot of normal skin thickness but with altered color
Diagnosis of Dermatologic Conditions
Most important symptoms for diagnosis
• Pruritis
• Symmetry (endocrine)
Diagnostic Methods • Skin scrape • Culture • Cytology • Intradermal skin test • Serology for IgE • Biopsy & histo (*)
Submitting a biopsy for derm issues
- signalment, complete dermatologic history and physical exam findings
- Fix specimens in 10% buffered formalin.
- use dermatopathologist in difficult cases.
- Send Photos!
Microscopic Changes on histo that help diagnose derm issues
- Pattern of cellular infiltrate
- Predominant cell type
- ID of a causative agent
Perivascular Inflammation; where is it, causes
o In the superficial dermis
Causes
• Allergies
• ectoparasites
Interface dermatitis; what is it, causes
o dermoepidermal junction obscured by cellular infiltrate and/or hydropic degeneration of basal epidermal cells
causes
• lupus erythematosus
• drug eruption
Vasculitis (of skin); what is it, causes
o multifocal hemorrhage and/or ulceration
Causes
• Immune complex deposition
• Sepsis
Folliculitis / Perifolliculitis; causes of primary vs secondary & furunculosis
o Often has pustules
Primary
• Dermatophytes (ring worm)
• Demodex canis mites
Secondary • Bacterial infection secondary to underlying condition • Allergy • Endocrinopathies • Trauma • Ectoparasites
Furunculosis
• hair follicle rupture which incites pyogranulomatous or granulomatous reaction
Nodular or diffuse dermatitis; what is it, causes
o Often pyo/granulomatous
Causes
• Infectious organisms: bacteria, fungi
• Foreign body: necrotic fat, suture, etc
Intraepidermal vesicles & pustules; what is it, causes
o Between layers of epidermis
Causes o pemphigus foliaceus o viral vesicular diseases o pemphigus vulgaris – DEEP intraepidermal o impetigo
Impetigo
- puppy pyoderma
- Superficial pustular dermatitis
- Most commonly coagulase-positive Staphylococcus
- Kittens – Pasteurella multocida
Subepidermal Vesicular Dz; where is it, causes
o Deep to epidermis
o Ex: bullous pemphigoid
Mechanisms of Alopecia
o Destruction of normal hair shaft
o Failure of cyclical hair growth (endocrine)
o Toxic or metabolic disturbances
Acanthosis; basics, gross & microscopic lesions
o Epidermal Hyperplasia
o Common non specific response to chronic injury
Gross Lesion
• Lichenification – thick & deep fissured skin
Microscopic Lesions
• Increased ancanthocyte layer
Secondary Seborrhea
o Scaling secondary to underlying dz
o Common
o May be accompanied by greasiness & foul odor
o Reaction to chronic process
o Hypothyroid, low humidity, ectoparasites, etc
Primary Seborrhea; basics & two forms
o Increased scale formation
o Primary defect in epidermal turnover
o Often breed specific & idiopathic (spaniels, hounds)
Seborrhea sica
• Dry skin w/ scaling
Seborrhea oleosa
• Greasy skin w/ scaling
Parakeratosis; basics, cause, histologic description
o dry, scaly skin
o zinc deficiency,
Histologic Diagnosis
• thickened stratum corneum; partially keratinized, still contain nuclei
Hyperpigmentation (melanosis); two forms
o Increased activity of melanocytes
Localized
• Chronic irritation
• Inflammation
Generalized
• Systemic stimulus such as hormones
Hypopigmentation; two forms
Congenital
• Albinism (tyrosine deficiency)
Aquired
• Localized
• Permanent loss of melanocytes
Surface Vs Superficial Vs Deep Pyoderma
Surface pyoderma
• Skin fold dermatitis
Superficial pyoderma • Short duration • Does not cause lymphadenopathy • Good prognosis • Ex: puppy impetigo
Deep pyoderma • Serious deep skin infection • Invades dermis +/- subcutis • Often chronic • May cause scarring • Often regional lymphadenomegaly • Usually secondary to underlying dz
Basics of skin fungal infections
o Often sporadic
o Associated w/ local debilitation or immunodeficiency
o Distinct geographic zones
o Usually not contagious
Deep Skin Mycoses; two forms
Cutaneous/subcutaneous • Traumatic implantation • nodular/diffuse dermatitis • granulomatous or pyogranulomatous • may require special stain • Ex: sporothricosis
Systemic infection spread to skin
• exist in soil or vegetation
• sporadic dz
• primary or opportunistic pathogens
Superficial Fungal Infections of Skin
- exception to many of the “rules“
- caused by several fungi that invade and destroy keratin
- tissue response may be mild
- often w/ secondary bacterial infection
- can see severe folliculitis & furunculosis
Malassezia; asics, clinical signs, diagnosis
- Commensal yeast isolated form ear & skin of healthy dogs
- Unipolar budding yeast (peanut shape on stained slides).
- Alterations in host defenses allows infection
Clinical Signs
• pruritus – often intense
• odor – “rancid fat”
• erythema - papules & macules
• generalized or localized
• scaling, crusting, ALOPECIA, greasy skin
• secondary lesions = lichenification & hyperpigmentation
Diagnosis
• Skin scrape or “scotch tape” impression
• Response to meds
Visible Skin Parasites
- Ticks, lice, flies, fleas
- Mild lesions
- Pruritis
- Flea saliva is allergen
4 Skin Mites
Cheyletiella
• Walking dandruff
• Mites walking on fur
Psoroptes
• Superficial
Sarcoptes
• Burrow in epidermis
• Very hard to find on scrape
• Very pruritic
Demodex canis
• Normal fauna in hair follicles of dogs
• Transmitted to pups at birth
• Can cause demodicosis
Localized Vs Generalized Demodicosis
Localized • Common in young dogs • small, circumscribed, erythematous, scaly, area of alopecia • non-pruritic OR pruritic • on face or forelimbs • resolves spontaneously
Generalized
• Severe disease
• Life-threatening secondary pyoderma
• Usually underlying cause
• Juvenile onset - Treat w/ Amitraz or Ivermectin
• Adult Onset - Poor prognosis in dogs >2yo
Diagnosis of Demodicosis
o Deep skin scraping reveals MANY mites
o Always rule out in any pyoderma case
Equine Cutaneous Habronemiasis (Summer Sores); basics & diagnosis
- deposition of larvae of Habronema sp. or Draschia sp. into skin wounds or moist areas of the body (by flies)
- rapidly growing, reddish brown granulation tissue
- numerous yellow granules can be expressed
- often pruritic
- medial canthus of the eye & prepuce / penis
Diagnosis
o Biopsy reveals granulomatous & eosinophilc inflammation +/- parasite larvae
Endocrine Dz of Skin; basics & clinical signs
o Most common in dogs
o Alopecia = primary change
o Too much or too little hormone
Clinical Signs • Bilaterally symmetric • Non-inflammatory • Non-pruritic • Gradual onset • Chronic • Usually truncal • Hair is easily removed • Often a secondary seborrhea • Can have bilaterally symmetrical hyperpigmentation
Urticaria
- Hives
- Type I hypersensitivity
- Dermal edema due to histamine mediated increase in vascular permeability
- Variably pruritic
Atopy; basics, lesions, diagnosis
- Common
- Genetic
- Pruritic
- Inhaled Ags
- Type I
- 9mo-3yo
- face rubbers & foot lickers
Lesions • Self trauma • Secondary pyoderma • Secondary seborrhea • Acanthosis
Diagnosis
• Intradermal skin test (gold standard)
• Serum IgE
Allergy Testing; baiscs, two tests
- Short shelf life
- Use if owner wants to pursue immunotherapy
Skin
• Measures cell bound allergen specific IgE
Serum
• Measures circulating allergen specific IgE
Flea Bite Hypersensitivity; basics & distribution
- most common hypersensitivity skin disorder in dogs & cats
- Type I and IV involved
- pruritic, papular and crusting dermatitis
- may be seasonal
Classic distribution • Looks like dog is wearing pants • dorsal lumbosacral • caudomedial thighs • ventral abdomen • flanks and neck
Food Allergy
- Pruritis: non-seasonal, +/- responsive to glucocorticoids
- 70% have no history of dietary change
- good prognosis IF you can identify and eliminate allergen
elimination diet
• ~10wks (3 wks not long enough)
• novel protein or hydrolysate
• then re-introduce diet and look for recurrence
Contact Hypersensitivity
- uncommon
- variably pruritic gross lesion = papules & macules
- sparsely haired skin in areas of contact
- Type IV hypersensitivity
- Diagnose w/patch test
Pemphigus; basics, pathogenesis, how to differentiate types
- Group of uncommon autoimmune diseases
- Fragile vesicles, bullae & pustules -> erosions and ulcers
Pathogenesis
• Auto Abs directed against desmosomes ->
• Disrupt keratin adhesion (acantholysis) ->
• Vesicles or bullae ->
• Inflammation ->
• Pustules
Differentiate Pemphigus Dz
• Severity
• Lesion distribution
• Site of acantholysis
