Q11

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

Q12

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

Q13

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)

Pass criteria:

  • Need 2 of first 4 to pass PLUS 2 others

Q14

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

Q15

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

2 effects:

  • 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


Q16

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

Pass Criteria:

  • Ca ++ increased  PO4 decreased + some idea of how these achieved OR additional other mechs

What are the other effects of PTH?

  1. decreased plasma phosphate: decreased POreabsorption in proximal tubules
  2. increased 1,25 dihydrocholecalciferol: renal  ( > Ca absorption)
  3. Over a longer time: increased osteoblastic and osteoclastic stimulation- prob anabolic

Pass Criteria:

  • Parathyroid related hormone- (prob fetal/ cartilage growth + teeth/ breast- skin) ?
  • PO4 < +1 other in either section

Q17

What are the effects of thyroid hormones on nervous and vascular systems?

  • CNS
    • Development CNS -cerebral cortex, basal ganglia cochlea
    • increased activity, mentation speed/ agitation (catechol / dop+ direct brain effects)
    • increased refexes
  • CVS
    • 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

Pass Criteria:

  • 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

Pass Criteria:

  • At least 2

Q18

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

Q19

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

Q20

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

Pass Criteria:

  • 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:
    • Surgery
    • Anxiety
    • Physical trauma
    • Haemorrhage
    • High K intake and Low Na intake
    • Standing
    • Constriction of IVC in thorax
    • 2hyperaldosteronism  (eg CCF, cirrhosis, nephrosis)

Pass Criteria:

  • 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

Pass Criteria:

  • Bolded