Endocrine 21 to 30
Describe the effects of increased aldosterone.
- Increased reabsorption of Na+ from urine, sweat, saliva and colonic contents
- Na+ retention in ECF
- K+ diuresis and depletion
- ECF volume expansion
- 3 out of 5 to pass
List factors that increase aldosterone secretion.
- Haemorrhage / physical trauma / ECV contraction / surgery
- Low Na+ intake
- High K+ intake
- Constriction of IVC in thorax
- Secondary hyperaldosteronism (CCF, cirrhosis, nephrosis)
- 3 out of 6 to pass
How is aldosterone secretion regulated?
- ACTH from the pituitary
- Renin from kidney, via angiotensin II
- Direct stimulatory effect of K+ on adrenal cortex
Describe the changes in ACTH secretion that occur in response to stress.
- Increased ACTH secretion
- Mediated through hypothalamus by CRH
- CRH produced in paraventricular nuclei, secreted in medial eminence and transported in portal hyperphysical vessels to anterior pituitary
- Multiple nerve endings converge on paraventricular nucleii
- Destruction of median eminence means stress response is blocked
- Bold PLUS 1 other
What are the physiological consequences of sudden cessation of steroid therapy after prolonged treatment?
- Low glucorticoid levels with inability to increase
- Prolonged exogenous glucocorticoid inhibits ACTH secretion. Normally a drop in resting corticoid levels stimulate ACTH secretion (feedback loop)
- Inhibitory effect pituitary and hypothalamus due action on DNA
- Degree of pituitary inhibition proportional to level glucocorticoid
- ACTH inhibiting activity of steroids parallels glucocorticoid potency
- Adrenal atrophic and unresponsive
- Pituitary unable to secrete normal amounts of ACTH for one month, probably secondary to decreased ACTH synthesis
- After one month a slow rise in ACTH levels to supranormal levels, stimulates adrenal with increased glucocorticoid output. Feedback inhibition causes a gradual decrease in ACTH levels to normal
- Avoid by tapering dose over long period
What are the effects of thyroid hormones?
- At least two organ systems and one effect on each
How are thyroid hormones synthesised?
- Active iodide transport;
- binding to thyroglobulin;
- MIT and D IT join to form T3 and T 4.
What is the mechanism of action of thyroid hormones?
- Enter cells;
- binds to specific receptors;
- hormone-receptor complex binds DNA & effects gene expression.
What hormones are produced by the pituitary?
- Knowledge of anterior and posterior pituitary with 4 of6 of the anterior pituitary (TSH, ACTH, GH, FSH, LH, prolactin) and one of vasopressin or oxytocin
What are the physiologic effects of vasopressin.
- Renal retention of water in excess of solute reducing body fluid osmolality or concept
What are the principal actions of insulin?
Storage of carbohydrate, prot and fat, varies with tissues Rapid- seconds. Glc, amino acids and K± into insulin sens cells
Intermediate- minutes. Stimulates prot synthesis, inhibits prot degradation, activates glycolytic enzymes & glycogen synthase, inhibits phosphorylase and gluconeogenic enzymes.
Delayed- Hrs. increase in mRNA for lipogenic & other enzymes
Ole and K from rapid.
Answer must reflect understanding of effects on carbohydrate, protein and fat
What happens when insulin binds to its receptor?
- Binds to a cell membrane-based stereospecific insulin receptor on insulin-sensitive cells
- Insulin binding triggers tyrosine kinase activity of f3 subunits —> autophosphorylation of J3
subunits on tyrosine residues
- The above reaction –>. phosphorylation and de-phosphorylation of proteins that are
effectors and secondary mediators.
Pass: Binding results in activation of secondary protein effectors (tyrosine kinase activity) and mediators. (phosphorylation)
Outline the steps in the synthesis of catecholamines.
Adrenaline ? Nor Adrenaline
PNMT (adrenal medulla, some central)
Pass: Tyrosine to dopamine to noradrenaline, plus one of the synthesis enzymes
What happens to noradrenaline after it is released into the synaptic cleft?
Removed by post-synaptic and pre-synaptic binding, reuptake and catabolism
IC) MAO decreased COMT (EC)
Pass: 3 out of 4 processes
What is the normal range of osmolality of ECF?
Pass: Accept 280-300
How is this maintained?
Maintained by Vasopressin-secreting and thirst mechanisms
If osm decreased, thirst is decreased, Vp secretion is decreased, resulting in urinary loss of free water
If osm increased, thirst is increased, Vp secretion is increased, leading to renal reabsorption of free water in renal collecting ducts/pyramids
Pass: 3 of 4 Bold
What other stimuli affect Vp secretion increased
Prompt: Anti-diuretic Hormone.
VP secretion increased by:
(increased effective plasma osm pressure)
decreased ECF volume (via low pressure receptors)
Pain, emotion, exercise, stress (eg surgery)
Nausea & vomiting
Pass: 2 of 4 Bold
VP secretion increased by:
(increased effective plasma osm pressure)
decreased ECF volume
Pass: 1 of 2 Bold
What are the physiologic effects of the glucocorticoids?
- Intermediary metabolism of carbohydrate, protein, fat
- Inhibit ACTH secretion
- Maintain reactivity of vascular (and bronchial) smooth muscle to catecholamines
- Allow excretion of a water load (mechanism unclear)
- Blood – Increased RCC, increased WCC (mainly PMNs), but , decreased Lymphocites and Lymph node size
- CNS — irritability, apprehension, inability to concentrate (eg in exams)
- “stress response”
(Up to 3 specific prompts, eg “what are the vascular effects of glucocorticoids?”)
Pass: 3 bold
Describe the steps in synthesis of thyroid hormones.
Prompt: What are thyroid hormones made from?
Thyroid epithelial cells secrete thyroglobulin (comprising 134 tyrosines) and iodine into colloid. Iodide transport is via a symport with sodium (NIS). Thyroid peroxidise makes iodotyrosines (MIT and DIT) then combines them to make T3 and T4. Some reverse T3 (inactive) also made. Endocytosis and lysis of colloid releases free hormone. All steps TSH controlled. T3 also made peripherally by deiodination of T4.
What are the physiological effects of T4?
Prompt: How do thyroid hormones alter metabolism?
Binds to intracellular thyroid receptors in the nuclei. Complex binds to DNA and alters gene expression. T3 more rapid and potent. Incr metabolism and catabolism of most cells (brain and others excluded). Lipid and carb mobilisation and usage. Inc CVS and CNS activity. Normal reproductive cycle and growth. Effects incr by catecholamines.
Pass: Core knowledge in bold. Subunits combine together
Which catecholamines act as neurotransmitters?
Noradrenaline, Adrenaline and Dopamine
Describe the sequence of events at a noradrenergic synapse, following stimulation of a sympathetic nerve.
Prompts: How is noradrenaline released? How is noradrenaline removed from the synaptic cleft? What enzymes are involved in the breakdown of noradrenaline?
Noradrenaline, which has been stored in granulated vesicles, is released into the synaptic cleft by
Noradrenaline acts on postsynaptic and to a lesser extent presynaptic and glial receptors.
In addition to binding to receptors, Noradrenaline is also removed from the synaptic cleft by:
• Reuptake into presynaptic neuron (via a Neuro Transmitter Transporter (NTT)) and then is broken down to inactive product by Monoamine Oxidase (MAO) located on mitochondria.
• Broken down to inactive product by Catechol-O-methyl transferase (COMT) located on the postsynaptic membrane.