Flashcards in Pathology of the Endocrine System 1 Deck (25):
INTERCELLULAR SIGNALLING: THREE GROUPS
1. AUTOCRINE SIGNALLING- Cells respond to signals they produce themselves.
2. PARACRINE SIGNALLING- Cells produce signals that act on the neighbouring cell- adjacent target cell.
3. EXOCRINE SIGNALLING- Exocrine glands/organs produce signals (hormones) that enter the circulation and act on distant target cells.
An endocrine gland is a group of specialised epithelial cells, which synthesise, store and directly release secretions in to blood vessels.
These secretions are polypeptides, steroids and amino acid derivatives.
They have a physiological effect on distant target cells.
MECHANISMS OF ENDOCRINE DISEASE
HYPOFUNCTION- Primary- Loss of secretory cells/biochemical defect in pathway. NB immune-mediated disease.
-Secondary- Destructive lesion targets trophic hormone production, decreasing activity in the target organ.
HYPERFUNCTION- Think tumours!
-Primary- abnormal cells secrete hormone too fast for body requirements.
-Secondary- abnormal cells in one organ produce too much trophic hormone, increasing activity in the target organ. eg. pituitary gland tumour.
OTHER POSSIBLE MECHANISMS OF ENDOCRINE DISEASE
-Endocrine dysfunction due to neoplasia- hypersecretion by NON-ENDOCRINE tumours. eg. pseudohyperparathyroidism- PTHrP is secreted by some tumour cells.
-Failure of target cell response- receptor dysfunction eg. insulin resistance in obese animals.
-Abnormal hormone degradation- eg. feminisation due to hyperoestrogenism.
CLINICAL RESULT OF ENDOCRINE DISEASE
Endocrine disease leads to functional disturbances and clinical pathology affecting on or more body systems:
-SKIN- alopecia or hirsutism
-NERVOUS SYSTEM- seizures
-URINARY SYSTEM- polyuria
-SKELETAL SYSTEM- fracture
ROLE OF THE HYPOTHALAMUS
'The Fat Controller'
Neurosecretory neurones produce RELEASING HORMONES, which are transported to the pituitary gland (hypophysis) via the hypophyseal portal circulation.
Releasing hormones produced:
Gonadotrophin releasing hormone (GnRH),
Corticotrophin releasing hormone (CRH),
Thyrotrophin releasing hormone (TRH),
Growth hormone releasing hormone (GHRH),
Growth hormone inhibiting hormone (GHIH, somatostatin),
Prolactin release inhibiting factor (PRIF, dopamine)
ROLE OF THE PITUITARY
aka. Hypophysis. Adenohypophysis- anterior pituitary. Neurohypophysis- posterior pituitary.
Responds to release hormones/factors from the hypothalamus, releasing hormones that go on to act on endocrine organs:
Adrenocorticotrophic hormone (ACTH)
Thyroid stimulating hormone (TSH)
FSH, LH- gonadotrophins
Melanocyte stimulating hormone (MSH)
The posterior pituitary (neurohypophysis) releases oxytocin and ADH, which are nonapeptides synthesised by neurones in the paraventricular or supraoptic nuclei of the HYPOTHALAMUS.
Anterior pitituiary. Comprised of:
-Pars tuberalis (dorsal projections of cells along infundibular stalk, provide scaffold for hypophyseal portal system capillary network)
-Pars intermedia (lines residual lumen of Rathke's pouch)
-Pars distalis (largest part, several pituitary trophic hormones act)
Posterior pituitary. Comprised of pars nervosa + infundibular stalk.
ANTERIOR PITUITARY HYPOFUNCTION
PRIMARY- aplasia/hypoplasia- can be congenital, toxic or viral.
-Destruction can occur secondary to space occupying lesion eg. cystic Rathke's pouch (if large, may cause central diabetes insipidus)/abscess/neoplasm.
SECONDARY- hypothalamic malfunction.
CONSEQUENCES OF ANTERIOR PITUITARY HYPOFUNCTION
-Decreased TSH -> decreased T3/4 -> hair coat alterations, altered metabolism and growth.
-Decreased GH -> altered metabolism and growth
-Decreased ACTH -> decreased cortisol -> delayed parturition, altered metabolism and growth.
-Decreased FHS/LH -> subfertility/infertility.
aka. Juvenile panhypopituitarism.
-Decreased growth rate; adults are less than 50% normal size
-Abnormal hair coat- retention of puppy coat then alopecia, bilaterally symmetrical alopecia, hyperpigmentation.
-Hypoplasia of gonads and genitalia.
-Delayed permanent dentition and epiphyseal closure.
Pituitary dwarfism can be unapparent until 2 months of age.
In certain breeds, can be caused by CONGENITAL CYSTS OF RATHKE'S POUCH- German shepherd, spitz, toy pinscher, Karelian bear dogs.
POSTERIOR PITUITARY HYPOFUNCTION
CLINICAL SYNDROME- DIABETES INSIPIDUS.
PRIMARY- caused by destruction of the neurohypophysis- no ADH is produced. Destruction could be due to trauma, neoplasia or congenital defects. This produces CENTRAL DI.
SECONDARY- nephrogenic DI- the nneurohypophysis is still functioning, but the renal tubules cannot respond to the ADH it makes.
ROLE OF ADH
Allows collecting ducts to reabsorb water.
Increases permeability of collecting tubules and ducts -> resorption of water -> production of concentrated urine.
More ADH = more water reabsorbed = less urine.
Clinical signs- PU/PD, low urine specific gravity (isosthenuria/hyposthenuria)
CENTRAL- defect in neurohypophysis means less ADH is produced, so water resorption decreases.
NEPHROGENIC- neurohypophysis is functioning and producing adequate ADH, but the renal tubules are insensitive to its action.
Lack of water resorption leads to dilute urine production, hypernatraemia and dehydration, which all go on to cause clinical signs of PU/PD.
Causes of central DI can include abscess, trauma or neoplasia affecting the pituitary.
Most commonly seen due to functional neoplasms within the pituitary:
Adenoma (benign)- most common in pars distalis in the dog, pars intermedia in the horse.
Also seen due to pituitary HYPERPLASIA in the dog and horse. -> pituitary dependent hyperadrenocorticism (one cause of Cushing's syndrome)
AMOUNT OF ACTH PRODUCED IS NOT RELATED TO TUMOUR SIZE.
ANTERIOR PITUITARY HYPERFUNCTION
Increased ACTH increases cortisol release from adrenal cortex.
-> alopecia, polyuria, altered metabolism, immune suppression (secondary infections)
Altered metabolism then leads to: increased protein catabolism and muscle wasting, increased appetite, increased glycogen metabolism in liver (leading to vacuolar hepatopathy)
PITUITARY HYPERPLASIA IN AGED DOGS
Common- hyperplastic nodules/microadenomas seen.
Causes hyperadrenocorticism- Cushing's syndrome.
Symptoms: Non-pruritic alopecia, comedones with dystrophic calcification, flaccid abdominal wall due to muscle wasting- fat belly. Alopecia is bilaterally symmetrical. Calcification.
Increased glucose and glycogen mobilisation -> vacuole formation in liver (visible histologically)
EQUINE PITUITARY HYPERPLASIA
Hyperplasia of PARS INTERMEDIA.
Common in aged horses.
Adenomatous hyperplasia, microadenomas, adenomas of pars intermedia.
-> Equine Pituitary Pars Intermedia Dysnunction (PPID) aka. Equine Cushing's.
This is NOT a true Cushing's syndrome. Diagnostic endocrinology does not always match histological findings on PM examination.
EQUINE CUSHING'S SYNDROME
Aged ponies, 15 years+
Pituitary bulges from sella turcica to put pressure on the hypothalamus.
Signs relate to DERANGED HYPOTHALAMIC FUNCTION- regulation of appetite, temperature, seasonal sleep rhythms, hair growth/shedding all disrupted.
-> PU/PD, polyphagia, hyperglycaemia, laminitis, generalised hyperhidrosis (sweating), somnolence, striking hypertrichosis/hirsutism.
PATHOGENESIS OF EQUINE PITUITARY PARS INTERMEDIA DYSFUNCTION (PPID)
Pressure atrophy and degeneration of hypothalamus
-> inability to control appetite- polyphagia.
-> excessive food intake- hyperinsulinaemia.
-> down regulation of insulin receptors on target cells.
-> insulin resistsnt hyperglycaemia -> glucosuria
PATHOGENESIS OF CLINICAL SIGNS OF EQUINE PPID
Failure of hypothalamic temperature control -> INTERMITTENT PYREXIA.
Failure of autonomic control -> EXCESSIVE SWEATING
Failure of cortisol regulation -> hypercortisolism -> LAMINITIS
Failure of immune response -> PYAEMIA (S. zooepidemicus)
The above failures are caused by atrophy/degeneration of the hypothalamus due to the pituitary bulging and putting pressure on it.
Adrenal cortex- 3 zones- zona glomerulosa, zona fasciculata, zona reticularis.
Produce ALDOSTERONE, CORTISOL and ANDGROGENS respectively.
Adrenal medulla produces catecholamines.
NORMAL adrenal glands shoudl show a 2:1 ratio of medulla to cortex.
ADRENAL CORTICAL HYPOFUNCTION
Hypofunction of the adrenal cortex will affect aldosterone, cortisol and androgens:
LOW ALDOSTERONE- potassium not excreted by kidney -> hyperkalaemia, sodium not resorbed by kidney -> hyponatraemia.
LOW CORTISOL- vomiting, diarrhoea, weakness, poor condition, lack of appropriate inflammatory response -> poor wound healing, lack of stress leukogram.
LOW ANDROGENS- subfertility.
aka. HYPOADRENOCORTICISM. Causes the clinical syndrome ADDISON'S DISEASE.
Caused by adrenal cortical atrophy- usually idiopathic, but can be due to any damage (infectious, vascular, drug induced etc), or secondary to pituitary hypofunction.