Pathophysiology of endocrine tissues Flashcards
eicosanoids, catecholamines and peptide hormones all act at what kind of receptor?
membrane receptor as they are water soluble
What kind of receptor do steroid hormones and thyroid hormone work at?
Intracellular receptor as they are lipid soluble and can cross the plasma membrane
What is primary hypofunction?
Failure of the gland itself to produce the hormone
What are the three main causes of hypofunction? (broadly)
destruction of the gland tissue e.g. abscess, granuloma etc embryonic failure of tissue development Defective synthesis eg lambs with congenital dishormogenic goitre
what is secondary hypofunction?
hypofunction of the gland sue to lack of stimulation by trophic hormones (may be abnormal or lacking). eg inactive pituitary –> hypofunction of adrenal and thyroid glands and hypoplasia of gonads
What is primary hyperfunction?
Hyperfunction of the gland usually due to hormone secreting tumour, e.g. hyperthyroidism in cats
What is secondary hyperfunction?
increased hormone production in response to increased trophic hormone e.g. ACTH-secreting pituitary adenomas leading to hypertrophy and hyperplasia of the adrenal cortex and cushings disease
Where is the hypothalamus situated?
In the basal part of the diencephalon beneath the thalamus
What is secreted from the anterior pituitary in response to GnRH?
FSH & LH
What is secreted from the anterior pituitary in response to GHRH?
Growth hormone
What is secreted from/inhibited at the anterior pituitary in response to Somatostatin?
Inhibits Growth hormone and TSH
What is secreted from/inhibited at the anterior pituitary in response to TRH?
TSH and Prolactin stimulated
What is secreted from/inhibited at the anterior pituitary in response to DA?
prolactin inhibited
What is secreted from/inhibited at the anterior pituitary in response to CRH?
ACTH
What is the connection between the hypothalamus and the anterior pituitary?
Portal blood vessel system
How are the hypothalamus and the posterior pituitary connected?
nerve fibres from the paraventricular and supraoptic nuclei of the hypothalamus run to the posterior pituitary
What hormones are produced by the posterior pituitary?
Oxytocin and Vasopressin (ADH)
What is the sella turcica?
the bony cavity at the base of the skull in which the pituitary sits
What are the five main cell types in the anterior pituitary?
Gonadotroph
Lactotroph
Somatotroph
Corticotroph
Thyrotroph
Lucy Cheetham Sucked Tilly’s Gonads
what are the three parts of the anterior pituitary?
pars tuberalis
pars distalis
pars intermedia
(pars nervosa is in posterior)
What are the three types of cells in the pars distalis?
Acidophils (lactotrophs,somatotrophs)
Basophils (thyrotrophs, gonadotrophs, corticotrophs)
Chromophobes
Where is ACTH secreted from in the dog?
Pars intermedia and pars distalis
How do you get pituitary cysts?
failure of the oropharyngeal ectoderm to differerntiate into hormone secreting cells of the pars distalis
What breeds are commonly effected by pituitary cysts?
GSDs, spitz, minpin
What are the signs seen with pituitary cysts?
Relatable to reduced trophic hormones
dwarfism (noticeable around 2m of age)
Puppy coat retention –> alopecia and hyperpigmentation
Delayed growth plate closure in long bones
Delayed dentition
Hypoplasia of thyroid and adrenals
Infantile reproductive organs/genitalia
Life span short if severely affected
Which species do pituitary adenomas occur in?
Horses and to a lesser extent dogs
(older animals)
What is the disease you get associated with hormonally active pituitary adenomas in dogs?
Hyperadrenocorticism (as ACTH produced)
What might happen if the pituitary adenoma gows to the extent that you get obliteration of the gland?
Hypopituitarism, commonly expressed as diabetes insipidus
What is the appearance of adnomas of adenomas of the pars intermedia in horses?
Large, multinodular, yellow/brown/white and firm
May compress the pars nervosa (posterior pituitary) and the overlying thalamus
What happens to plasma cortisol levels in horses with PPID?
normally normal or slightly raised. Different precursor metabolism to in dogs (POMC)
What are the three hormones normally produced from POMC in the pars intermedia in horses?
CLIP, MSH, B-endorphin
What is mainly produced in the pars distalis in the horse from POMC?
ACTH
What parts of the pituitary can an ACTH secreting adenoma arise from in the dog?
distalis or intermedia
Which breeds are predisposed to ACTH secreting adenoma in dogs?
Boston Terrier
Boxer
Dachshund
What happens to the adrenal gland physically in cushings disease in dogs?
The adrenal cortex has bilateral enlargement, adrenals show yellow/orange coloured nodules of variable size which may compress the corticomedullary junction. Similar nodules in fat around the glands
What does an ACTH secreting adenoma in the dog look like on histology?
nests of chromophobe cells
Fine connective tissue stroma
No secretory granules seen on light microscopy
What are the four vague ststemic effects of ACTH secreting adenoma in the dog?
Gluconeogenesis
Lipolysis
Protein catabolism
Anti-inflammatory actions
What are the clinical signs seen with ACTH secreting adenoma in the dog?
Abdominal enlargement
Muscle wasting
Enlarged liver
Bilateral alopecia
Thin skin with hyperpigmentation
Fat pads around neck and shoulders
Poor wound healing
What are the two main hormones secreted by the pars nervosa?
Oxytocin
Vasopressin
Where are oxytocin and vasopressin synthesised (exactly)
Nerve cell bodies of the suproptic and paraventicular nuclei of the hypothalamus
How long is the half life of oxytocin and vasopressin?
About 5 mins
Circulate at very low levels
How do oxytocin and vasopressin act?
G protien coupled plasma membrane receptor
How do you get central diabetes insipidus?
Inadequat production or release of ADH
Which part of the pituitary needs to be damaged to cause central diabetes insipidus?
Pars nervosa needs to be obliterated or compressed by an expanding cyst or tumour
Why does damage to the hypothalamus have the potential to cause central diabetes insipidus?
Can cause inadequate production as ADH made there (SON, PVN)
What is the main clinical sign associated with diabetes insipidus?
Marked PU/PD, very hypotonic urine
What is the main stay of diagnosis in diabetes insipidus?
Water deprivation test and assessment of response to exogenous ADH
What is nephrogenic diabetes insipidus?
Unrelated to pituitary disease, is caused by an inability of the epithelium in the collecting ducts to utilise ADH
What does the adrenal cortex secrete?
Glucocorticoids
Mineralocorticoids
small amount of sex steroids
What does the adrenal medulla secrete?
Adrenaline and Noradrenaline (catecholamines)
What are the zones of the adrenal cortex called?
glomerulosa
fasciculata
reticularis
(GFR)
What is produced in the zona glomerulosa?
Mineralocorticoid e.g. aldosterone
What is produced in the zona fasciculata?
Glucocorticoid e.g. cortisol
What is produced in the zona reticularis?
Androgens e.g. oestradiol
What kind of hormone is cortisol and what is its roll?
Cortisol is a glucorticoid (from adrenal zona fasciculata) and is for dealing with stressful events e.g. trauma, starvation, infection etc
What are the effects on the body of cortisol?
Stress response - increased vascular tone
Immunosuppressive and antiinflammatory actions
Increased mobilisation of fatty acids from skeletal muscle
Liver has increased gluconeogenesis, glycogenesis, glycogen storage, and enzyme activity
Increased mobilisation of glycerol and fatty acids from dat cells
What are mineralocortcoids regulated by?
RAAS
plasma sodium and potassium levels
What does aldosterone do?
Conservation of body sodium by exchanging for potassium in the kidney
Which species commonly get mineralisation of the adrenal glands?
adult cats and monkeys
Which species commonly get amyloidosis of the adrenal glands?
old mice, rats and monkeys
Name two diseases which can cause adrenalitis (abscesses/disseminated disease of adrenals)
NB adrenalitis really means inflammtion of one or both adrenal glands
Toxoplasmosis and Tuberculosis
Which of the adrenal products is vastly increased in cushings disease?
excessive glucocorticoids (e.g. cortisol)
What percentage of cushings syndrome cases in dogs are caused by a pituitary tumour?
80%
Why do you get a pot bellied appearance in cushings?
Due to hepatomegaly and abdominal muscle weakness
What is the appearance of nodular adrenocortical hyperplasia?
What groups does nodular adrenocortical hyperplasia occur in?
older dogs cats and horses. Similar nodules in liver, spleen and pancreas
What is the histological appearance of the nodules in adrenocortical nodular hyperplasia?
resemble the zona glomerulosa or fasciculata
What is the appearance of diffuse adrenocortical hyperplasia?
adrenal cortex uniformaly enlarged
normally due to ACTH secreting pituitary tumour but can be idiopathic
What does diffuse adrenocortical hyperplasia look like on microscopy?
hypertrophy and hyperplasia of the zona fasciculata and reticularis
cells are often vacuolated due to richness in lipids
What is being described?
mainly old dogs
single pale yellow/red nodule, partially or completely encapsulated, surrounding tissue may be compressed, sometimes in both glands
adrenocortical adenoma
What is the microscopic appearance of an adrenocortical adenoma?
Cells resemble either zona fasciculata or reticularis
Vacuolated, divided by fibrovascular stroma
Image shows capsule on the left
How do you differentiate adrenocotrical adenoma from adrenocortical nodular hyperplasia?
Adenoma tends to be singular, encapsulated and compressive
Which products of the adrenal cortex are decreased in primary hypoadrenocorticism?
both glucocorticoids and mineralocorticoids
What is primary hypoadrenocorticism caused by and which groups are most often affected?
Destruction of the adrenals
Idiopathic bilateral adrenocortical atrophy
Autoimmune reaction or inflammatory disease
Young adults are mainly affected and all three layers of cortex are affected
Effects are mainly due to lack of mineralocorticoid, therefore altered mineral balance
What are the effects of primary hypoadrenocorticism?
Increased excretion of Sodium, Calcium and Water
Haemoconcentration and dehydration
Increased potassium in the blood-DANGER slows the heart
Generalised tissue under perfusion
V & D
Reduction of glucocorticoids - susceptible to stressful events
What are the three hormones secreted by the thyroid gland?
Thyroxine
Tri-iodothyronine
Calcitonin
What are T3 and T4 attached to?
Thyroglobulin
Where are T3 and T4 stored? (bound to thyroglobulin)
In the colloid part
What do the C cells/parafollicular cells do?
Secrete calcitonin
What is the pathway by which T3 and T4 release is stimulated?
TRH from hyopthalamus
TSH from pituitary
acts on thyroid to cause release of T3 and T4
Which is the more potent thyroid hormone? T3 or T4? Where is the less potent one converted into the more potent one?
T3 is the most potent
Target tissues have a deiodinase enzyme to covnert T4 to T3
Pituitary can also do this to facilitate negative feedback
Which hypothalamic hormone inhibits TSH release?
Somatostatin
What is the effect of thyroid hormones?
Caloregenic by increasing BMR
Increased cardiac output
Alterations in metabolism
Iodide enters te thyroid epithelial cell by the ___a___ __a__ which is dependent on ___b___ and is situated on the _____c____ membrane
It then diffuses into the __d__ across the ___e___ membrane
a) iodide pump
b) cAMP
c) basolateral
d) colloid
e) apical
The enzyme ____a___ then combines Iodide and tyrosine to form T3 and T4 which are bound to __b___
a) TPO-thyroid peroxidase
b) thyroglobulin
T3 is made up of one__a__ and one __b__
T4 is made up of two __c__
a) monoiodothyronine
b) diiodothyronine
c) diiodothronine
Colloid droplets are lysed in the ___a___ and MIT and DIT provide more iodide by the action of the enzyme ___b___
a) epithelial cell
b) deiodinase
What is the definition of a goitre?
What is a dyshormogenetic goitre?
congenital inability to make T3 T4 in certain breeds of sheep. Will have rough sparse coats and die quickly
What are the four broad causes of a goitre?
Genetic enzyme defect (eg lambs dyshormogenetic goitre)
Iodine deficiency (calves least susceptible)
Iodine excess (foals from dams fed dried seaweed)
Goitrogenic substances-Brassica plants, some sulphonamides
What is the microscopic appearance of a goitre?
Diffuse hyperplasia of the follicles
Rate of colloid excreted eventually slows down and follicular cells become flat and less active. Unused colloid becomes prominent, called an involuted colloid goitre (see pic)
What are the three main causes of hyperthyroidism in cats?
Thyoird gland hyperplasia
Thyroid gland adenoma
autoimmune disease - Graves disease
What are the symptoms of hyperthyroidism?
Weight loss
Polyphagia
Unkempt coat
Tremor
pos Goitre
Agitated and Nervous
Fast heart rate, pos atrial fibrillation
Muscle weakness
Dyspnea
Heat intolerance due to excess heat production
Staring eyes
V+ D+ (due to thyroid hormone stimulation of CRTZ)
PU/PD
Info: multifocal nodular hyperplasia seen in cats dogs and horses (old)
Nocapsule and no compressino o adjacent tissue
Hyperplastic folicales seen histologically often with very little colloid
Can be hormonally active in cats
fg
What are the two most common causes of hypothyroidism?
Idiopathic atrophy
Immune mediated thyroiditis
What does idiopathic thyroid atrophy look like histologically?
Atrophy of the thyroid follicles (reduced in number and size), prominent connective tissue and fat cells
what causes immune mediated thyroiditis?
autoantibodies binding to thyrogloblin
what does immune mediated thyroiditis look like histologically?
infiltration of lymphocytes, plasma cells, macrophages
Degeneration of follicular cells
Name three less common causes of hypothyroidism?
bilateral non functioning thyroid tumours
severe iodine deficiency
destructive lesions of pituitary gland
