Exam 3 Flashcards
(142 cards)
1
Q
2 Types of Bone Formation
A
Endochondral
• bone formation on a cartilage template
• Ex: growth plate or fracture repair
Intramembranous
• formation from a loose fibrous framework
2
Q
Requirements for complete repair of bone
A
- Limited motion
- Adequate vascularity
- Sterility
- Apposition
- Adequate host nutritional status
3
Q
Secondary Lesions in Bone
A
- “reactive” new bone (infection, neoplasia)
- microfractures, compression fractures (physes)
- hemorrhages (physes)
4
Q
3 Techniques for Examination of Bone
A
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
5
Q
Basics of Secondary Bone Healing
A
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
6
Q
Inflammatory Phase of 2nd Bone Healing
A
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
7
Q
Repair Phase of 2nd Bone Healing
A
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
8
Q
Remodeling Phase of 2nd Bone Healing
A
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
9
Q
Primary Bone Healing; requirements, 2 subtypes
A
o no callus formation
Requirements
• Adequate blood supply
• Rigid immobilization
(most important)
• Excellent reduction and anatomic alignment
Subtypes
• Contact
• Gap
10
Q
Osteomyelitis; what is it? clinical signs?
A
o Inflammation of the bone
o Usually caused by infection
Clinical Symptoms • Lameness • Paresis • Draining tracts • Fever
11
Q
Osteomyelitis; tissue response, sequestrum
A
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
12
Q
Osteomyelitis Sequestra in horses
A
- 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
13
Q
Causes of Osteomyelitis
A
- Trauma
- Direct extension from infected site
Hematogenous
• Often multifocal
• Bacteremia
Specific Organisms
• Aerobic or anaerobic bacteria
• Fungi
14
Q
Vertebral Osteomyelitis
A
o Causes posterior paresis in pigs
Paresis due to:
• Pathologic fracture
• Myelomalacia
• myelitis
15
Q
Nutritional Bone Dz; Common lesions & nutritional components
A
Common Lesions
• Osteopenia (bone loss)
• Bone deformities
• Pathologic fractures
Common Nutritional Components • Common in exotics • Fad diets • Economic stress • Mixing errors
16
Q
Basics of Metabolic Bone Dz
A
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
17
Q
Forms of Metabolic Bone Dz
A
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
18
Q
Osteoporosis; basics, causes, examples of causes
A
- 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
19
Q
Osteomalacia; pathogenesis, lesions, compensation, causes, clinical signs
A
• 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
20
Q
Rickets; causes, clinical signs
A
- Juvenile form of osteomalacia
- Inadequate mineralization of osteoid & cartilage
Causes
• Vit D deficiency
• Phosphorus deficiency
Clinical Signs
• Lameness
• Enlarged metaphyses
• Pathologic fractures
21
Q
Rickets pathogenesis
A
- 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
22
Q
Fibrous Osteodystrophy; pathogenesis & clinical signs
A
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
23
Q
Two Causes/paths of Secondary Hyperparathyroidism
A
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
24
Q
Primary Vs Psuedo Hyperparathyroidism
A
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)
25
Chondrodysplasia; basics & example
* Defective cartilage formation
* inherited
* unequal
growth across physis
* endochondral ossification
* irregular, haphazard columns of chondrocytes
* EX: snorter calves (short & smushed face)
26
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
27
6 Bone Tumors
Osteosarcoma
• Common & important
Other primary neoplasias
• Fibrosarcoma
• hemangiosarcoma
Metasttic tumors
Chondrosarcoma
• 2nd most common
benign tumors of bone
• uncommon
28
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
29
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
30
Osteosarcoma in the Axial Skeleton
* Uncommon
* Most common site is maxilla
* May have longer survival rate than appendicular
31
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
32
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
33
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
```
34
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
35
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
36
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
37
Common Sites Herniated Disks
* T11 – L3 (mostly)
* Cervical
* Where there is not intercapital ligaments
38
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
39
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
40
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
```
41
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
42
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
```
43
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
```
44
Vertebral Osteomyelitis; basics, symptoms
o Hematogenous
o Bacterial caused
o Localized in epiphysis
Symptoms
• Paresis/paralysis
• Spinal cord compression
• Myelitis
45
Diskospondylitis
o Infection of intervertebral disc w/ osteomyelitis of contiguous vertebrae
o Hematogenous
o Bacterial caused
46
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)
47
Repair Cartilage in Place of Articular Cartilage
```
o fibrous (fibrocartilage)
o hypercellular
o Type I collagen predominates
o diminished glycosaminoglycans
o inferior substitute
```
48
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
49
Periarticular (perichondral) Bone Response to Injury
o Cartilagenous nodules ->
o Converted to bone via endochondral ossification =
o Periarticular osteophytes
50
Synovial Fluid Response to Injury
```
o Increased quantity of fluid
o Inflammatory cells
o Fibrin & immunoglobulin
o Synovial cells
o Change in viscosity
```
51
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)
52
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
```
53
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
54
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
55
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
56
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
57
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
58
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)
```
59
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
60
How is the endocrine system regulated
o Negative feedback is primary control mechanism
o Hierarchical levels of regulation
o Cross communication btwn endocrine organs
61
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
62
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
63
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
64
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)
65
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
66
Diseases of the Adenohypophysis of the pituitary
Hypopituitarism:
• deficient pituitary hormonal activity
Hyperpituitarism:
• excess pituitary hormonal activity
67
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
68
Hyperpituitarism; usual cause, example diseases
* Often caused by neoplasia
* Pituitary pars intermedia dysfunction (Equine)
* Pituitary-origin canine Cushing’s syndrome
69
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)
70
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
71
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
72
Diseases of Neurohypophysis of the pituitary
diabetes insipidus
* Neurogenic
* Nephrogenic
73
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
74
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)
```
75
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
```
76
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
77
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.
78
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)
79
Typical Addison's Disease; primary lesion & two precursors to pathophysiology
Primary Lesion
o Adrenal cortical atrophy/necrosis
Pathophysiology
o Idiopathic
o Iatrogenic
80
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
81
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
82
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
83
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
84
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)
85
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
86
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
87
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
88
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
```
89
What happens if Diabetes Mellitus is left untreated
* Ketoacidosis & ketonuria ->
* Osmotic polyuria ->
* Shock & acidosis ->
* Osmotic cellular dehydration ->
* Diabetic coma
90
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
```
91
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
92
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
93
Excess Insulin; species, causes, clinical signs
• Ferrets > dogs >>> 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
94
Typical Addison's Disease; deficiencies and results thereof
```
Deficient cortisol
• Leukocytosis
• Neutrophelia
• Eosinophilia
• Hypocholesterolemia
• Hyponatremia
```
Deficient ALD
• Hyponatremia
• Hyperkalemia
95
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)
```
96
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
97
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
```
98
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
99
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
100
Neoplasias of the thyroid
Thyroid follicular adenoma
o Unilateral w/ contralateral atrophy
o Causes hyperthyroidism
Follicular carcinoma
o Usually not function
o Dogs > cats
101
Function & cells of the parathyroid gland
Chief cells
• Produce PTH
• Prevent hypocalcemia
102
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
103
Main Clinical Finding of Hyperparathyroidism
* Fibrous osteodystrophy
| * Osteoporosis or Osteomalacia PLUS Intertrabecular Fibrosis
104
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
```
105
Clinical signs of primary & pseudo Hyperparathyroidism
* Mild/absent signs
* Bradycardia
* PU/PD
* Urinary calculi
* Metastatic mineralization
106
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
107
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 (*)
```
108
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!
109
Microscopic Changes on histo that help diagnose derm issues
* Pattern of cellular infiltrate
* Predominant cell type
* ID of a causative agent
110
Perivascular Inflammation; where is it, causes
o In the superficial dermis
Causes
• Allergies
• ectoparasites
111
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
112
Vasculitis (of skin); what is it, causes
o multifocal hemorrhage and/or ulceration
Causes
• Immune complex deposition
• Sepsis
113
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
114
Nodular or diffuse dermatitis; what is it, causes
o Often pyo/granulomatous
Causes
• Infectious organisms: bacteria, fungi
• Foreign body: necrotic fat, suture, etc
115
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
```
116
Impetigo
* puppy pyoderma
* Superficial pustular dermatitis
* Most commonly coagulase-positive Staphylococcus
* Kittens – Pasteurella multocida
117
Subepidermal Vesicular Dz; where is it, causes
o Deep to epidermis
| o Ex: bullous pemphigoid
118
Mechanisms of Alopecia
o Destruction of normal hair shaft
o Failure of cyclical hair growth (endocrine)
o Toxic or metabolic disturbances
119
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
120
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
121
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
122
Parakeratosis; basics, cause, histologic description
o dry, scaly skin
o zinc deficiency,
Histologic Diagnosis
• thickened stratum corneum; partially keratinized, still contain nuclei
123
Hyperpigmentation (melanosis); two forms
o Increased activity of melanocytes
Localized
• Chronic irritation
• Inflammation
Generalized
• Systemic stimulus such as hormones
124
Hypopigmentation; two forms
Congenital
• Albinism (tyrosine deficiency)
Aquired
• Localized
• Permanent loss of melanocytes
125
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
```
126
Basics of skin fungal infections
o Often sporadic
o Associated w/ local debilitation or immunodeficiency
o Distinct geographic zones
o Usually not contagious
127
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
128
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
129
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
130
Visible Skin Parasites
* Ticks, lice, flies, fleas
* Mild lesions
* Pruritis
* Flea saliva is allergen
131
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
132
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
133
Diagnosis of Demodicosis
o Deep skin scraping reveals MANY mites
| o Always rule out in any pyoderma case
134
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
135
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
```
136
Urticaria
* Hives
* Type I hypersensitivity
* Dermal edema due to histamine mediated increase in vascular permeability
* Variably pruritic
137
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
138
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
139
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
```
140
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
141
Contact Hypersensitivity
* uncommon
* variably pruritic
gross lesion = papules & macules
* sparsely haired skin in areas of contact
* Type IV hypersensitivity
* Diagnose w/patch test
142
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
