physiology 3A

• Endocrine System


  System that uses hormones as chemical messengers to coordinate and regulate the body's physiological processes
• Hormone


  Long distance chemical mediator secreted by an endocrine gland into the blood, which transports it to its target cell
• Hormones are produced by a gland and signal via transport within the circulatory system, while neurotransmitters are released across a neuromuscular junction or synapse and act over a short distance
• Feedback Loops


  • Direct Feedback Loops have a single control point
  • First Order have a single feedback loop via a signalling centre
  • Second Order have two control points
  • Third Order have three control points

  
• Feedback Loops in Biology

  • Positive Feedback
  • Negative Feedback

  
• Positive Feedback Loop


  Amplifies the initial stimulus, normally needs a defined end
• Negative Feedback Loop


  Reduces the stimulus, can be infinite
• Positive Feedback Loop - Oxytocin


  1. Initial Stimulus: first contractions

  2. Stretch sensitive neurones in the cervix

  3. Released from the posterior pituitary gland

  4. Oxytocin causes uterine muscles to contract

  5. After labour, the stretch is lost, Oxytocin production slows, Contractions stop
• Enzyme Linked Receptor


  Reduces the Stimulus
• The Adrenaline Response


  1. A neuronal signal triggers adrenaline release from vesicles in the medulla of the adrenal gland which release into the blood

  2. Vasoconstriction, increased heart rate

  3. Insulin suppression, amino acid & NEFAs release

  4. Sensitisation of the CNS
• Adrenaline (Epinephrine)


  Produced in the adrenal gland medulla, converted from noradrenaline by the enzyme PNMT which is only expressed when high levels of glucocorticoids (like cortisol) are present
• The adrenal gland medulla develops from the neural crest
• Investigating the Impact of Shift Work

  • Melatonin in urine (ng)
• The pineal gland produces melatonin and the adrenal gland produces cortisol, which have diurnal rhythm regulation and their balance regulates sleep
• Shift workers report insomnia partially because of the severe disruption to their diurnal cycles
• Hyper-


  Too much
• Hypo-


  Too little
• • mia


  In the blood
• Hyperglycemia


  Too much glucose in the blood
• Cellular basis of hormone action

  1. Hormone (H) binds to Receptor (R) to form Hormone-Receptor (H-R) complex

  2. H-R complex becomes activated (H-R*)

  3. Activated complex causes Target cell RESPONSE
• Hormone Deficiency


  Reduced Hormone (H) and Receptor (R) binding, reduced Target cell RESPONSE
• Hormone Excess


  Increased Hormone (H) and Receptor (R) binding, exaggerated Target cell RESPONSE
• Hormone Resistance


  Reduced Target cell RESPONSE despite normal Hormone (H) and Receptor (R) binding
• Constitutively Active Receptor


  Receptor (R) is activated without Hormone (H) binding, causing exaggerated Target cell RESPONSE
• Hormone Inhibitors


  Overcompensation risk, dose must be titrated
• Hormone Receptor Antagonists

  Block hormone action, not synthesis, overcompensation risk, dose must be titrated, hydrophobic analogues active orally, hydrophilic analogues must bypass stomach
• Hormone Replacement Therapy


  Overcompensation risk, dose must be titrated, hydrophobic analogues active orally, hydrophilic analogues must bypass stomach (due to stomach acid and enzymes)
• Diabetes (Type I)

  Insulin Dependent Diabetes, as a result of the pancreas not producing (enough) insulin, cause only partially known, at least in part autoimmune

  
• Diabetes (Type II)

  Blood glucose often too high, insulin resistant diabetes, both genetic and environmental inputs, desensitisation of the insulin receptor

  
• Hyperthyroidism

  Grave's Disease - the thyroid is attacked by the immune system and produces T3 and T4 in response, diet high in iodine, thyroid enlargement (goiter) is not a cause
• Hyperthyroidism

  1. Excessive Production of Thyroid Hormone

  2. Phamocological inhibition of thyroid hormone synthesis

  3. Radio-iodine

  4. Surgery (partial or complete thyroid removal) - what is the consequence of this?
• Cushing's Disease

  Pituitary gland benign tumours - excessive ACTH produced, the adrenal gland produces excessive cortisol, treated by slow removal of steroid medication, tumour removal, cortisol blockers
• Addison's Disease

  Adrenal Insufficiency (primarily cortisol and aldosterone), destruction of the adrenal cortex (normally autoimmune, also cancerous growth or surgical removal), secondary Addison's Disease caused by damage to the pituitary gland, treated by steroid replacement