Endocrine 11 to 20
What are the physiological effects of glucocorticoids?
- Metabolic; increased protein catabolism, increased hepatic glycogenesis and gluconeogenesis (raised plasma glucose). Raise peripheral tissue insulin resistance
- Permissive effects on other reactions
- Are required for catecholamines to produce calorigenic and lipolytic effects,pressor responses (vascular reactivity) and vasodilatation
- Inhibit ACTH secretion (feedback)
- Impair water excretion (mechanism unclear)
- Reduce circulating basophils and eosinophils and increase other elements
- Required for stress response
- Affect EEG waveforms (mild personality changes in insufficiency)
How is glucocorticoid secretion regulated?
- Basal secretion and stress response both dependent on ACTH
- (Other substances may stimulate adrenal directly but no evidence of role in physiologic regulation)
- Free glucocorticoids produce negative feedback on ACTH secretion at both hypothalamic and pituitary levels. Effect mediated by action on DNA
- Stress response ACTH secretion mediated almost exclusively via hypothalamic release of corticotrophin releasing hormone
- Circadian rhythm. ACTH released in irregular bursts throughout day but much more common in early morning. 75% of cortisol secreted at this time
Describe the effects of insulin on various tissues.
- Adipose: glucose in, fatty acid + glycerol synthesis, TG deposition, K in
- Muscle: glucose in, glycogen synthesis, Aas in, protein synthesis, ketones in, K in
- Liver: glycogen, protein + lipid synthesis,
- General: cell growth
What is the time frame for these effects?
- Rapid: glucose, AAs, K into sensitive cells
- Intermediate: protein synthesis, glycolysis and synthesis, inhibition gluconeogenesis
- Delayed: lipogenesis
What are the effects of thyroid hormones on different body tissues?
Prompt: What are the effects of thyroid hormone on the heart?
- Heart: chronotropic, inotropic (increased beta receptors, enhanced response to catecholamines)
- Adipose tissue: catabolic (lipolysis)
- Musculoskeletal: catabolic (increased protein breakdown), developmental (promote growth and development)
- Most (except adult brain, uterus, testes, spleen): calorigenic (increased O2 consumption of metabolically active tissues)
- CNS: developmental (promotes brain development)
- GIT: metabolic (increased carbohydrate absorption)
- Lipoprotein: metabolic (increased LDL receptors)
- Need 2 of first 4 to pass PLUS 2 others
How do the effects of noradrenaline and adrenaline differ on the cardiovascular system?
- BP: norad; ad
- HR: norad; ad
- CO: norad; ad
- TPR: norad; ad
How do the effects of adrenaline differ with serum concentration?
- Low concentrations – some beta effects, high concentrations alpha predominates
Describe the typical serum / urine effects in hyperaldosteronism?
- Na/ Cl mild increased, fluid retention (follows Na),
- decreased K, alkalosis (alkalaemia only if K+ depletes)
- Urine K+/ H increased
How does aldosterone exert its effects in the kidney?
- Mineralocorticoid- Via Principal cells- collecting ducts
- Genomic- Intracellular to nuc signalling > mRNA
- a) Inc ENAC insertion/ activity (quick)
- b) > production (slow)
- Membrane bind IP3 mediated Na/K exchange >
All = > Na reabsorb K/H loss to urine
What are the actions of the parathyroid hormone on Calcium?
- PTH increased plasma Ca++ by:
- increased Ca++ mobilization increased bone reabsorption,
- increased Ca++ reabsorption in distal tubule and (3) Ca reabsorption
- Ca ++ increased PO4 decreased + some idea of how these achieved OR additional other mechs
What are the other effects of PTH?
- decreased plasma phosphate: decreased PO4 reabsorption in proximal tubules
- increased 1,25 dihydrocholecalciferol: renal ( > Ca absorption)
- Over a longer time: increased osteoblastic and osteoclastic stimulation- prob anabolic
- Parathyroid related hormone- (prob fetal/ cartilage growth + teeth/ breast- skin) ?
- PO4 < +1 other in either section
What are the effects of thyroid hormones on nervous and vascular systems?
- Development CNS -cerebral cortex, basal ganglia cochlea
- increased activity, mentation speed/ agitation (catechol / dop+ direct brain effects)
- increased refexes
- 1)vasodil (2ary heat)
- > circ vol/ HR/ CO
- Ht- > myosin heavy chain (+ isoforms)/ faster twitch genes (+ Ca ++, Na K ATPase etc?) + down reg others, > contraction/ HR/ speed of contraction
- > sens to Catechols (synergistic effects + up regulated ß receptors and effector systems) HR, contract more
- 3-4 overall at least 1 in each
What other physiological effects does thyroid hormone have on the body?
- Lipolysis – adipose tissue
- Formation of LDL receptors on lipoprotein
- Protein breakdown in muscle
- Skeletal development promoted
- Increased carbohydrate absorption from the gut
- Stimulates O2 consumption by metabolically active tissues
- Increased BSL/ insulin resistance
- At least 2
Describe the effects of Vasopressin.
- Retention of water (antidiuretic hormone) (V2 receptors)
- Vasoconstrictor effect (V1A receptors)
- Central effect brain (area postrema) to decrease CO
- Glycogenolysis in liver (V1A receptors)
- Mediate increased ACTH secretion (V1B receptors)
- Neurotransmitter in brain and spinal cord
How does vasopressin cause retention of water?
- Increases permeability of CD, acting on V2 receptors
- Insertion of protein water channels (aquaporin 2) in uminal membranes.
- Water enters hypertonic interstitium
- Urine becomes concentrated and volume decreases
- Retention of water in excess of solute
What stimuli affect vasopressin secretion?
- Factors increasing vasopressin secretion
- increased effective osmotic pressure of plasma
- decreased ECF volume
- Pain, emotion, “stress”, exercise, standing
- Nausea and vomiting
- Clofibrate, carbamezepine, angiotensin 2
- Factors decreasing vasopressin secretion
- decreased effective osmotic pressure of plasma
- increased ECF volume
What happens when insulin binds to an insulin receptor?
- Insulin receptor: tetramer – 2 alpha and 2 beta glycosolated subunits
alpha subunits extracellular + bind insulin; beta subunits span membrane, intracellular parts have tyrosine kinase activity
- Insulin binding triggers tyrosine kinase activity of beta subunits -> autophosphorylation of beta subunits on tyrosine residues
- -> phosphorylation and de-phosphorylation of proteins
- -> Effectors and secondary mediators – Insulin receptor substrate (IRS-1);phosphoinositol 3-kinase (PI3K)
- Once bound, insulin receptors aggregate in patches and are endocytosed -> enter lysosomes -> broken down or recycled
- Peak effect 30 minutes IV / 1 hour oral
What are the principal actions of insulin?
- Net effect: storage of CHO, protein and fat
- Rapid (seconds): increased transport of glucose, amino acids and K into insulin-sensitive cells
- Intermediate (minutes): stimulation of protein synthesis and inhibition of protein degradation; activation of glycolytic enzymes and glycogen synthase;inhibition of phosphorylase and gluconeogenic enzymes
- Delayed (hours): mRNAs for lipogenic\other enzymes
Describe the actions of Aldosterone?
- Increase reabsorption of Na+ from urine
- Acts on principal cells (P cells) of collecting ducts, leading to increased amounts of Na+ exchanged for K+ and H+ in renal tubules, producing a K+diuresis and fall in urine pH
- Increase reabsorption of Na+ from sweat, saliva and colon
- Aldosterone cause retention of Na+ in ECF leading to ECF volume expansion
List the stimuli that increase aldosterone secretion?
- ACTH from pituitary
- Renin from kidney via angiotensin II
- Direct stimulatory effect of rise in plasma K+ concentration on adrenal cortex
- Clinical causes:
- Physical trauma
- High K intake and Low Na intake
- Constriction of IVC in thorax
- 20 hyperaldosteronism (eg CCF, cirrhosis, nephrosis)
- Bolded PLUS 2 others
Describe the feedback regulation of aldosterone secretion?
- Fall in ECF / blood volume -> reflex increase in renal nerve discharge &decrease in renal artery pressure
- -> increase in renin secretion -> increase in angiotensin II -> increase in aldosterone secretion
- -> Na+ & water retention -> expanded ECF volume -> decrease in stimulus that initiated renin secretion