Vet Pathology-Disturbances of Growth

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Involution

normal (physiologic) decrease in size of an organ or tissue

Atrophy

decrease in the amoutn of tissue after normal growth has been attained, reduced tissue mass due to decreased number of cells and/or reduced cell size, extrinsic factors.

Abiotrophy

progressive degeneration of cells resulting from an intrinsic defect in cell metabolism, cells develop normally, then degenerate

Hypoplasia

failure of an organ to reach normal size, incomplete growth

Aplasia

reduction in organ growth manifested as markedly reduced or rudimentary organ size, also used to indicate failure to form certain adult tisses that are continually replaced

Agenesis

Complete failure of a tissue or organ to develop

Atresia

absence or closure of a normal opening

Hypertrophy

increased size of a tissue or organ due to an increase in the size of individual cells, term also used to indicate gross enlargement of an organ

Hyperplasia

increase in organ size or tissue mass due to increased number of cells

Dysplasia

abnormal development of tissue, loss of normal architectural orientation of cells, loss of cellular uniformity

Metaplasia

transformation of a differentiated tissue type into a related type of tissue

Anaplasia

reversion of a cell to a less differentiated type

What are 2 mechanisms of atrophy?

numerical: decrease in the number of cells due to cell death
Quantitative: decrease in the size of individual cells

What are 3 types of atrophy?

involution, generalized and localized

What are some examples of involution atrophy?

1. fetal life (branchial clefts, notochord, thyroglossal duct)
2. Postpartum (ductus arteriosus, umbilical artery and vein, urachus)
3. Mature animals (thymus, Bursa of Fabricius, ovarian follicles, lymphoid tissue in man)
4. Cyclic involution (assoc with reproduction, endometrium and vasculature, myometrium, mammary gland)

What are some examples of generalized atrophy?

1. nutritional causes (inadequate food intake, poor quaity feed, GI obstruction, paarasitism, GI malabsorptive disease)
2. Chronic Wasting Disease (TB, Johne's, cancer, nutrient deficiencies)

What is the proposed mechanism for generalized atrophy of chronic wasting?

infectious agents, trauma, cancer --> stimulation of macrophages, monocytes --> secretion of cachectin (TNF-alpha) -->
1. hypothalamus --> decreased appetitie and delayed gastric emptying
2. insulin resistance --> decreased anabolism
3. increased glucocorticoids --> increased catabolism
---> emaciation, compounded by animal's inability to obtain food due to weakness or decreased competitiveness

What is the gross appearance of generalized atrophy?

* generalized muscle wasting, thin, weak.
* fatty liver in early stages, then small liver with grey wrinkled capsule
* serous atrophy of fat (appears grossly as clear to yellow, watery to gelatinous, flaccid material at sites of fat accumulation. Microscopically the fat has an eosinophilic appearance due to potassium soaps and edema

ischemic atrophy

gradual progressive loss of blood supply

pressure atrophy

compression causes loss of blood supply

Disuse atrophy

usually quantitative and reversible, skeletal muscle

Neurogenic atrophy

variant disuse atrophy due to denervation

Sweeny

damage to suprascapular nerve atrophy of supraspinatous muscle

Laryngeal hemiplegia

trauma to L. recurrent laryngeal nerve atrophy to cricoarytenoideua dorsalis muscle

Neoplasm atrophy

enlarging neoplasm --> damage to trigeminal nerve --> atrophy of muscles of mastication

Endocrine atrophy

decrease in trophic hormones, hypoopituitarism testicular atrophy

What is the gross appearance of localized atrophy?

organ appears smaller than normal for the size of the animal, easier to ID in paired organs, grey wrinkled surface of parenchymal organs

What is the microscopic appearance of localized atrophy?

Quantitative: looks hypercellular, too many nuclei per field.
Numerical: necrosis or loss of cells

What does the liver look like in localized atrophy?

hepatic cords thinner than normal, more lobules fill the field than normal, lots of fibrous CT, scarring

What does the pancreas look like in localized atrophy?

hypercellular

What does striated muscle look like in localized atrophy?

thin myocytes

What does the kidney look like in localized atrophy?

tubular atrophy appearance of too many glomeruli

What does the spleen look like in localized atrophy?

too few lymphoid follicles, wrinkled capsule

What is the sequela to localized atrophy?

1. fatty atrophy (fatty infiltration)
2. fibrous atrophy, CT tissue replacement
3. pigment atrophy (deposit of lipofuscin pigment
4. signs attributable to organ dysfunction

What is the most common occurrence of abiotrophy?

degenerative disease of the CNS
1. cerebellar degeneration
2. lysosomal storage diseases
3. neuroaxonal degeneration

Also...
1. degenerative diseases of muscle - muscular distrophy

What is cerebellar abiotrophy?

abiotrophy: animal normal at birth then signs of ataxia develop weeks to months later, cerebellum may be normal to smaller, degeneration and loss of Purkinje cells, may have the loss of granular cells

What is the mechanism for Fluoride toxicosis in ruminants?

increase in fluoride --> inhibitory effect on ameloblasts and odontoblasts --> abnormal mineralization of matrix --> enamel hypomineralization

What is a specific cause of cerebellar hypoplasia in kittens and how does it produce this lesion?

panleukopenia virus, develops in utero

What is a specific cause of cerebellar hypoplasia in calves adn how does it produce this legion?

bovine virus diarrhea virus, develops in utero

What are some causes of hypoplasia?

genetic and viral

What are some examples of hypoplasia?

lymphatic system, testicular (heritable), ovaries (heritable), intestine, cerebellum (virus), enamel (fluoride toxicosis)

Atresia coli

absence of closure of loops of intestine

Atresia ani

no anal opening

Hypertrophy vs. hyperplasia

hypertrophy of many organs often involves boht hypertrophy and hyperplasia. hypertrophy alone occurs in organs with low mitotic capabillities (cardiac muscle)

What is the cause of hypertrophy?

increased demand for function

What are the 2 classifications of hypertrophy?

1. physiological or hormonal hypertrophy (mammary gland, uterus, testes in seasonal breeders)
2. adaptive hypertrophy (striated muscle, smooth muscle, kidney)

What is the gross and microscopic appearance of hypertrophy?

gross: organ larger than normal for the size of the animal
microscopic: may have enlarged cells

What is the sequelae to hypertrophy?

associated with increased demand for function, if the demand is removed, there is a regression of the hypertrophic process

What are some causes of hyperplasia of epithelial cells in skin?

chronic irritation, chronic infection, viral, Zn deficiency, healing wounds, chlorinated naphthalene toxicosis

What is the mechanism for hyperplasia of epithelium of skin?

disturbances in the normal balance of growth factors (GF) that stimulate and inhibit epithelial cell proliferation.
Increase stimulatory: basic fibroblast GF, transforming GF-a, Keratinocyte GF
decrease inhibitory: transforming GF-b, TNF-a, interferons

What are 3 causes of hyperplastic thyroid?

1. Iodine deficiency
2. Iodine excess
3. goitrogenic plants

What is the microscopic appearance of hyperplastic goiter?

increase number of follicles, follicles have irregular size and shape, follicles lined by single or multiple layers of hypertrophic cells

What is the mircoscopic appearance of colloid goiter?

increase number of cells, follicles markedly distended with colloid and lined by flattened cells

What are some characteristics of bone marrow hyperplasia?

increase production of hematopoietic cells, esp seen with regenerative anemia, both RBC and WBC proliferate
gross: red marrow
micro: increase cellularity

What is a cause for lymphoid tissue hyperplasia?

antigenic stimulation

What is the gross and micro appearance of lymph node hyperplasia?

gross: enlarged LN, may see white foci
micro: follicles larger than normal

What is the gross and micro appearance of spleen hyperplasia?

gross: single or multiple, well circumscribed raised nodules, red or pale
micro: focal area of lymphoid proliferation

How does iodine deficiency cause thyroid hyperplasia?

Low I2 low thyroxine inc. thyroid stimulating hormone (TSH) hypertrophy initially, progresses to hyperplasia. Mother can transmit this to the fetus so that the fetus is deficient in iodine.

How does iodine excess cause thyroid hyperplasia?

High I2 interference with thyroxine production at multiple steps low thyroxine inc. TSH hypertrophy, hyperplasia

How does Vitamin D deficiency effect calcium homeostasis?

Deficiency of vitamin D --> inadequate synthesis of calcium-binding protein --> inadequate absorption of calcium hypocalcemia --> deficient mineralization of bone and parathyroid hyperplasia in growing animals, see abnormal mineralization at physes with gross deformities and fractures in bones +/- fibrous osteodystrophy; in adults, see decreased mineralization, softening and fractures in bones +/- fibrous osteodystrophy.

How does a diet high in phosphorus effect calcium homeostasis?

causes hypocalcemia

How does renal disease effect calcium homeostasis?

Increase phosphorus retention due to decrease GFR. The conversion of 25-OH-D3 to 1,25-diOH-D3 occurs in the kidney, with kidney disease there will be decreased conversion and decreased calcium absorption from intestine due to decreased calcium binding protein --> hypocalcemia

What do low dietary calcium, high dietary phosphorus, vit D deficiency and renal disease lead to?

Parathyroid gland hyperplasia

Vit D def., low Ca and renal disease --> dec Ca absorption -->hypoocalcemia (high P) --> excessive stimulation of parathyroid gland --> increase secretion of PTH --> increase Ca resorption from bone fibrous CT proliferation

Vit D def lesions

bones soft, cortex thick, fibrous tissue in marrow

psuedohyperaparathyroidism lesion

humoral hypercalcemia of malignancy. Neoplasms produce a hormone which has PTH-like activity, hormone acts alone or in concert with cytokines to increase Ca++

Primary hyperparathyroidism lesion

functional adenoma - rare

Nutritional secondary hyperparathyroidism lesion

Big head, horse, swine, monkey, maxillary bones thick and soft

Renal secondary hyperparathyroidism lesion

renal rickets, rubber jaw

How do viruses cause hyperplasia of epithelial cells of the skin?

...

What are some examples of metaplasia?

1. epithelium, cubodial to stratified squamous
2. CT: fibrous CT to cartilage or bone

What is the mechanism for metaplasia?

progenitor cells differentiate along a different line

What are 3 causes of epithelial metaplasia?

1. chronic irritation: chronic bronchitis or prostatitis
2. hormonal: inc estrogens cause prostatic metaplasia
3. Nutritional def: vit A def, lesions in cornea, conjuctiva, kidney, respiratory tract and parotid duct

What is the pathogenesis of vit A def?

• Rhodopsin deficiency nightblindness.
• Modulation defects in osteoblast stem cells increased numbers of osteoblasts increased appositional bone growth abnormal bones.
• Modulation defects in basal epithelial cells squamous metaplasia and increased keratinization secondary bacterial infection (especially of respiratory and urinary tracts)
• Defects in arachnoid granulations decreased reabsorption of CSF elevated CSF pressure hydrocephalus.
• Abnormal fetal development anomalies and fetal death.

Where does dysplasia commonly occur?

kidney, neoplasms

Where does anaplasia commonly occur?

1. CT, of embryonic characteristics - mucoid degeneration, myxomatosis
2. neoplasms- failure of malignancy

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