Endocrine 31 to 40
What are the main effects of insulin?
1. Increased glucose into cells (adipose, liver, muscle)
2. Protein synthesis
4. K into cells
Pass: 3 of 4
What is the mechanism of action of insulin?
Insulin binds to insulin receptors on insulin sensitive cells, triggers autophosphorylation of the insulin receptor which is necessary for the insulin effects. There is receptor mediated endocytosis into the cell and the insulin-receptor complexes trigger cytoplasmic proteins to produce various other proteins. There are at least 4 insulin related substrate (IRS) proteins in cells.
Pass: Must describe that insulin binds to receptor and is taken into cell where secondary mediators are formed.
What hormones are secreted by the adrenal medulla?
Adrenalin, noradrenalin and dopamine.
Pass: Must have all 3
What are the major effects of these hormones?
- alpha and ß effects.
- increase HR and force contraction, vasoconstriction, hypertension, alertness, metabolic rate, glycogenolysis
Pass: Must describe at least 5 effects
What are the effects of glucocorticoids?
Action on intermediary metabolism of carbo, proteins, fats. Permissive action for glucagon, catecholamines — calorigenic, lipolytic, pressor, bronchodilator, vascular reactivity. CNS vs irritability, apprehension, inability to concentrate. Renal — excretion of water by increased GFR. Anti-inflammatory vs cytokines. Resistance to ‘stress’ —noxious stimuli increasing ACTH.
How are they metabolised? How are they controlled?
Cortisol liver, conjugated to glucuronic acid; inactivation depressed by liver disease
Name the endogenous catecholamines. Where are they produced?
PROMPT – Match catecholamines with source.
- Adrenal medulla
- Intrinsic Cardiac Adrenergic Cells
- Sympathetic Nervous System Cells
- Bold to pass
What are the physiological effects of adrenaline and noradrenaline?
- Increased metabolic rate
- Mobilisation of free fatty acids
- Increased lactic acid
- Vasoconstriction and dilation
- Increase heart rate and strength
- Alpha 1: Constriction of blood vessels, smooth muscles (especially noradrenaline)
- Alpha 2: Mixed smooth muscle effects (especially adrenaline)
- Beta 1: Cardiac ionotropy and chronotropy, irritability (both)
- Beta 2: Dilation blood vessels liver & muscle, other smooth muscle relaxation (adrenaline)
- Beta 3: Lipolysis, detrusor relaxation (especially adrenaline)
- 1 metabolic
- 1 bold cardiovascular
List the physiological effects of glucocorticoids.
- Increased protein catabolism
- Increased hepatic glycogenolysis and gluconeogenesis, increased glucose-6-phosphatase –> increased plasma glucose
- Anti-insulin effects on peripheral tissues
- Inhibit ACTH secretion
- Controls vascular reactivity to noradrenaline and adrenaline
- Control ability to excrete water load
- Increased neutrophils/platelets/red blood cells and decreased eosinophils/lymphocytes/basophils
- 2 bold and 2 others
What are the vascular effects of abruptly stopping long term glucocorticoids?
- Vascular smooth muscle becomes unresponsive to noradrenaline and adrenaline
- Capillaries dilate and increased permeability
- Failure to respond to noradrenaline impairs vascular compensation for hypovolaemia and promotes vascular collapse
- Must have general concept
What is the benefit of elevated glucocorticoid levels in stress?
- Effect on vascular activity to catecholamines plus necessary for catecholamines to mobilise free fatty acids for emergency energy source
What are the physiological effects of glucocorticoids?
- Permissive action
- Catecholamine effects – pressor/vascular reactivity
- Increase protein catabolism
- Increase hepatic glycogenolysis and gluconeogenesis -> increase in plasma glucose
- Anti-insulin effects on peripheral tissues
- Increase lipolysis
- Free water excretion (decreased vasopressin)
- Decreased inflammation/allergic response/ lymphocyte activity
- Haematological – increase neutrophils/platelets/red blood cells
- EEG slowing
- Personality changes
- 2 metabolic
- 1 other
How is glucocorticoid secretion regulated?
- Glucocorticoids (cortisol) – secreted from the adrenal cortex; secretion dependent on ACTH secretion from the anterior pituitary
- ACTH secretion is regulated by CRH released from the hypothalamus in response to low cortisol levels or stress)
- Glucocorticoids provide a negative feedback loop on the hypothalamus and the anterior pituitary to reduce ACTH secretion
How is plasma calcium regulated?
- 1,25-dihydroxycholecalciferol (from vit D) increases Ca absorption from gut & kidneys
- PTH mobilises Ca from bone, increased Ca reabsorption in kidney, increased 1,25 DHCC formation in kidneys
- Calcitonin (from thyroid) inhibits bone resorption, increases Ca excretion in urine
- 2 of 3 bold to pass
How is the synthesis of 1,25-dihyroxycholecalciferol (vit D) regulated?
- 1,25-DHCC formed in kidney by 1a-hydroxylase
- High Ca/high PO4 in 1,25-DHCC (increases inactive 24,25-DHCC instead)
- Low ca increases PTH which stimulates 1a-hydroxylase (low PO4 directly stimulates 1a-hydroxylase)
How are thyroid hormones regulated?
Prompt: Describe the feedback mechanism
Prompt: What factors affect TSH secretion?
- TRH from the hypothalamus stimulates TSH from the anterior pituitary which, in turn, stimulates the production of T4 (and a small amount of T3) from the thyroid gland
- Negative feedback of TSH by free T3 and T4 (act on the hypothalamus and pituitary gland – the effect of T3 is greater than T4)
- TSH secretion is affected by factors in the following ways:
- Increased by cold
- Decreased by warmth (especially in infants)
- Decreased by stress and glucocorticoids
- Decreased by dopamine and somatostatin
- Bold and concept to pass
- At least one factor that affects TSH secretion to pass
Other than cardiovascular, what are the physiological effects of thyroid hormones?
- Calorigenic: Increased metabolic rate, increased stimulation of O2 consumption
- Adipose tissue: Catabolic (stimulated lipolysis)
- Muscle: Catabolic (Increased protein breakdown)
- Bone: Promote normal growth and skeletal development
- Nervous System: Promote normal brain development and mentaion
- Gut: Metabolic (increased carbohydrate absorption
- Cholesterol: formation of LDL receptors and removal of circulating cholesterol
- Bold plus one other system