Flashcards in Endocrine disorders 2 of 2 Deck (26)
the adrenal gland is made up of the adrenal medulla and the adrenal cortex. outline the hormones secreted from each part and their action in the body.
1) Secreted by the adrenal medulla: Adrenaline
- Secretion in response to stress and exercise, Increases heart rate.
2) Secreted by adrenal cortex: Cortisol
- Essential for adaptation to stress.
- Mobilizes glucose
- Anti-inflammatory actions (at high levels).
3) Secreted by adrenal cortex; Aldosterone.
- Maintains balance of Na/K in blood.
Cortisol modulates carbohydrate, fat and protein metabolism. outline the main metabolic effects of cortisol
1) Opposes effects of insulin: in muscle, adipose and lymphoid tissues it is catabolic (in the liver it stimulates storage of glycogen (anabolic).
2) Increases plasma glucose levels by stimulating gluconeogenesis in the liver.
3) Decreases glucose utilisation in other tissues.
4) Increased plasma glucose is used for the production of glycogen -important for the maintenance of liver glycogen during prolonged fasting.
outline the effects of cortisol on the immune system and how can this be used to our advantage?
1) cortisol is an immunosuppressant
2) Anti-inflammatory: suppresses tissue responses to injury which decreases number of circulating lymphocytes which leads to decreased antibody production and impaired cellular and humoral immunity
3) These anti-inflammatory effects have lead to the widespread use of glucocorticoids in medicine.
Cushing's syndrome (hypercortisolism) is a collection of symptoms caused by very high levels of a hormone called cortisol in the body. why does this syndrome lead to weight gain?
cortisol Stimulates appetite
describe the role of the (H-P-A axis) hypothalamic–pituitary–adrenal axis
1) corticotropin releasing hormone (CRH) secreted from the hypothalamus stimulates production of corticotropin (ACTH) from the anterior pituitary
2) corticotropin stimulates secretion of cortisol by adrenal cortex
3) cortisol negatively feeds back on the pituitary where it inhibits release of corticotropin and also on the hypothalamus where it inhibits release of CRH
how does steroid medication inhibit the HPA axis? hypothalamic–pituitary–adrenal axis
adds to the pool of cortisol. increased levels of cortisol it feeds back negatively on both the pituitary and the hypothalamus. so it reduces the levels of ACTH and CRH
Dysfunctions of the HPA axis can lead to the over production of cortisol leading to a disease complex called Cushing syndrome. what problems in the HPA axis cause Cushing syndrome?
Normally caused by a benign tumour of the pituitary:
1) May be as a result of excess CRH production which drives ACTH secretion which in turn stimulates excess release of cortisol. e.g. from a CRH-producing tumour
2) May be as a result of excess ACTH production from an ACTH-producing tumour “ectopic tumour”- most frequently in the lung.
3) Adrenal tumour
4) Cushing syndrome is most often an extreme side-effect of steroid medication.
list the symptoms of Cushing syndrome
1) Central obesity
2) Thinning of the skin
3) Bruising (due to capillary fragility)
4) Hypertension (stimulates aldosterone production)
5) Muscle and bone wasting
how is cushings syndrome diagnosed?
1) Measurement of cortisol/ACTH levels in urine/plasma.
2) Normal/very low ACTH concentration – ACTH independent e.g. adrenal tumour or the use of steroid medication.
3) High ACTH concentration - probably due to an ectopic ACTH-producing tumour.
4) Moderately high ACTH levels - tends to be due to a pituitary tumour
5) Dexamethasone suppression test: Low dose will suppress ACTH levels in normal patients but not in Cushing’s Disease. However, suppression often seen in high dose dexamethasone test.
6) Sample blood from inferior petrosal sinus. Blood from pituitary drains into here and can sample with a catheter – shows source of ACTH.
outline the treatment for cushings syndrome
Depends on cause:
1) Reduce steroid medication
2) Surgical removal of the tumour.
3) Adrenalectomy - leads to high levels of POMC peptides due to lack of negative feedback - leads to hyperpigmentation - called Nelson’s syndrome.
what disease is cause by a lack of adrenal hormones? and what is the cause?
1) Addison’s Disease
2) Loss of adrenal function – often autoimmune
what are the symptoms of Addison’s Disease?
1) Tiredness and weakness.
2) Anorexia and vomiting due to lack of cortisol.
3) Loss of sodium reabsorption in the distal tubule of the kidney leads to low sodium and high potassium levels in the plasma. This leads eventually to hypotension and collapse.
4) High levels of ACTH are secreted to try to compensate. Other POMC peptides that are co-secreted cause patients to become hyperpigmented - especially in skin creases.
What is the treatment for Addison’s disease?
1) Administration of mineralocorticoids such as fluorocortisol.
2) Administration of hydrocortisone to replace cortisol.
why should treatment with corticosteroids not be stopped abruptly?
Exogenous corticosteroid medication results in down-regulation of the HPA axis. As a consequence treatment can not be abruptly stopped as it takes time for the axis to restart. this can lead to an Addisonian crisis
what can excess corticosteroid medication lead to?
Excess corticosteroid medication can result in the symptoms of Cushing’s Syndrome
vasopressin (ADH) is released from the Posterior Pituitary. what is its role?
1) Reduces water excretion by kidney
2) Is a potent vasoconstrictor at higher doses
- A nonapeptide with short half life (~5mins). Circulates as free peptide and is cleared mainly by kidney
what stimulates the production of vasopressin?
1) Main physiological stimulus: increased osmotic pressure of blood
2) Other stimuli: Fall in blood volume, Reduced arterial pO2, Raised arterial pCO2, Raised temperatur, Pain, trauma, infection
what are the main actions of vasopressin at normal concentrations?
1) at normal concs on renal nephron: Increase permeability of renal distal convoluted tube and collecting ducts to water.
-More water readsorped from tubule
-Reduced urine output; more concentrated
-Restoration of blood osmolarity and volume.
what are the actions of vasopressin at high concentrations?
1) on blood vessels: Constriction of blood vessels
- Raise Blood Pressure
1) what disease does hyposecretion of ADH lead to?
2) what are the symptoms?
3) what is the cause?
-Vasopressin, also known as antidiuretic hormone (ADH)
1) Hyposecretion :Diabetes Insipidus
2) Reduced ADH :less water re-uptake, more urination, increased plasma osmolality,dehydration
3) Symptoms: Polyurea, Polydipsia- thirst and excessive drinking
4) Causes: Neurogenic -brain/pit trauma
-Nephrogenic – (kidney insensitivity)
what is the treatment for Hyposecretion of ADH?
1) replacement therapy with synthetic ADH analogue (Desmopressin)
2) Usually given as a nasal spray but can be given by injection (IV, SC, IM) and also an orally active form (much larger doses)
1) what does hypersecretion of ADH lead to?
2) what are the symptoms?
3) what is the cause?
1) Hypersecretion : Syndrome of inappropriate ADH (SIADH)
2) Symptoms: decrease in frequency of urination
- excessive fluid retention
3) Causes: Physiological - Cold, stress, anxiety, pain, trauma
-Pathological – ADH secreting tumour, Brain disorder/damage
what is the treatment for Hypersecretion of ADH?
1) Limit fluid intake to 500ml/day
2) Tumour removal?
3) Treatment with antibiotic Demeclocycline which has side effect of blocking action of ADH at kidney.
Oxytocin is released from the Posterior Pituitary. what is its role?
1) First recognised for its ability to promote delivery of
young. Causes contraction of uterine smooth muscle
2) Used to induce uterine contractions during parturition (drug:“syntocin”)
3) Also involved in “milk ejection reflex”:Causes contraction of smooth muscle-type cells surrounding milk ducts of mammary gland
describe how the Neuroendocrine reflex controls milk ejection
1) Tactile stimulation of nipple (i.e. during suckling)
2) Sensory nerves stimulates producton of oxytocin from oxytocin-producing magnocellular neurones
3) Discharge of oxytocin from nerve terminals in Post. Pit.
4) Transport via blood to myo-epithelial cells (ME cells) lining alveoli of Mammary Gland
5) Contraction of ME cells raises pressure in alveoli squeezing milk into ducts and cistern.
6) Sudden rise in intramammary pressure can cause milk to squirt from nipple/teat