Test 2 Key Processes

• Stretch Reflex = Activation of intrafusal spindle fibres

  • Muscle spindle stretched so afferent neurone stimulated to fire
  • Monosynaptic connection in spinal cord leads to agonist muscle activation
  • Inhibition of antagonistic muscle through inhibitory interneurone
• Cross bridge cycling

  • Myosin sites blocked on actin
  • ATP hydrolysed to ADP + Pi which causes a conformational change - changes angle of myosin head by 45
  • Calcium binds to troponin which leads to tropomyosin uncovering myosin binding sites
  • Phosphate is released which causes another conformational change - leads to powerstroke and myosin heads moving along actin and shortening the sarcomere
  • ATP binds to myosin which releases actin and the process begins again
• Excitation-Contraction coupling

  • Action potential is propogated along the membrane and down the T-tubule
  • Dihydropyridine receptors are mechanically coupled to ryanoide receptors
  • Release of calcium from DHPRs cause the release of calcium from ryanodine receptors into sarcoplasm
  • Leads to cross-bridge cycling and contraction
  • Calcium is pumped back into sarcoplasmic reticulum by SERCA
• Calcium induced calcium release

  • Action potential opens up voltage-gated sodium channels causing and influx of sodium ions
  • DHPR opens when recognising positive change in membrane potential - leads to calcium release
  • Ryanodine receptors open and release calcium
  • Increases calcium ions in cytoplasm and so leads to contraction
• Smooth muscle excitation-contraction coupling

  • Calcium enters the sarcoplasm via action potential propogation
  • Triggers ryanodine receptors to release calcium from sarcoplasmic reticulum
  • Calcium binds to calmodulin and forms a calcium-calmodulin complex
  • Activates myosin light chain kinase which phosphorylates the regulatory light chain of myosin
  • Increases ATPase activity which stimulates cross-bridge cycling
  • CAMP/cGMP upregulates myosin light chain phosphotase which prevents actin and myosin binding
• Thyroid hormone formation

  • TSH binds to follicular cells + stimulate production of thyroglobulin
  • Thyroglobulin is released into the colloid which causes TSH to stimulate the uptake of iodide ions into follicular cells via the Na⁺/I⁻ symporter
  • Thyroid peroxidase converts I⁻ into I₂ via oxidation
  • Iodine is transported into colloid to bind to thyroglobulin via pendrin transporter
  • Iodine binds to tyrosine via TPO to form MIT and DIT
  • TPO joins the two monomers to form T3 and T4
• Regulation of thyroid hormone

  • Stimuli e.g stress causes TRH to be released by hypothalamus
  • Travels down to anterior pituitary and interacts with Gq linked TRH receptor
  • Produce TSH which is released from the anterior pituitary into the thyroid gland and binds to TSH receptor
  • TSH receptor activated both Gq and Gs which activates the production of thyroid hormones which play a key role in:
  • Increasing metabolic rate and heat production
  • Enhancement of growth and CNS developemnt
  • Enhancement of sympathetic activity
• Mechanism of thyroid receptor action

  • RXR and TR binds to a co-repressor which suppresses gene transcription until needed
  • T3 binds to thyroid receptor which removes the co-repressor which recruits other proteins known as co-activators
  • These activate gene transcription and increase protein expression
• Regulating calcium levels

  1. High levels of Ca²⁺ in blood stimulates thyroid gland parafollicular cells to release more calcitonin
  2. Calcitonin promotes movement of blood calcium into bone matrix - reduces Ca²⁺ levels in the blood
  3. Low levels of Ca²⁺ in the blood stimulates parathyroid gland principal cells to release more PTH
  4. Parathyroid hormone promotes release of Ca²⁺ from bone matrix to blood and slows loss of calcium in urine - increases Ca²⁺ in the blood
  5. PTH stimulates kidneys to release calcitriol which stimulates increased absorption of calcium from foods - increases blood Ca²⁺
• Glomerular filtration

  1. Afferent arteriole carries blood plasma to the capillaries of the glomerulus
  2. Pressure forces the plasma from capillaries into the Bowman’s capsule (most proteins have been removed by this filtration)
  3. Filtered plasma enters the proximal tubule
• Inhibition of HCl release

  1. Luminal acid stimulates somatostatin release from D cell
  2. Somatostatin directly inhibits HCl release by binding to parietal cell
  3. Somatostatin indirectly inhibits HCl release by binding to G cells (prevents gastrin release)
  4. It also indirectly inhibits HCl release by binding to ECL cells (prevents histamine release)
• Regulation of HCl secretion

  1. Parasympathetic vagus nerve releases ACh which binds to muscarinic receptors on ECL cells and parietal cells
  2. ECL cells release histamine which increases HCl secretion
  3. Vagus nerve also stimulates gastrin release from G cell
  4. Gastrin directly stimulates HCl secretion by binding receptors on the parietal cell
  5. Gastrin indirectly stimulates HCl secretion by binding to receptors on ECL cells which increases histamine
• Mechanism for HCl secretion

  1. Carbon dioxide enters parietal cell from interstitial fluid
  2. CO₂ bind to H₂O to form H₂SO₃ which is hydrolysed into H⁺ and HCO₃⁻ via carbonic anhydrase
  3. Na⁺/K⁺-ATPase creates electrochemical gradient by pumping Na⁺ out of the parietal cell and K⁺ in
  4. HCO₃⁻ leaves parietal cell via HCO₃⁻-Cl⁻ antiporter which brings Cl⁻ into the parietal cell
  5. H⁺ leaves parietal cell into lumen via proton pumps which brings K⁺ into the cell (ATP required)
  6. K⁺ leaves the cell via K⁺ pump and Cl⁻ leaves via Cl⁻ channel
  7. Cl⁻ + H⁺ → HCl in the lumen
• RAA system

  1. Baroreceptors in juxtaglomerular cells detect decrease in BP and chemoreceptors in macula densa detect decrease in [Na⁺]
  2. Liver produces angiotensinogen which is converted into angiotensin I via enzyme renin (from kidney)
  3. Angiotensin converting enzyme from lungs converts angiotensin I into angiotensin II
  4. Angiotensin II stimulates production of aldosterone from adrenal gland → increases Na⁺ reabsorption in distal convulated tubules
  5. This increases water reabsorption increasing blood volume and BP
• Effects of Angiotensin II

  1. Angiotensin II stimulates ADH release from posterior pituitary → water leaves from DCT and collecting duct
  2. It also increases vasoconstriction in arterioles (increases BP) + glomerular filtration + sympathetic activity
• Micturition reflex

  1. Reflex control = Bladder fills with urine when initiated via stimulation of stretch receptors within the bladder wall
  2. Stretch receptors send impulses into the spinal cord which stimulates parasympathetic nerve and motor neurones
  3. Parasympathetic nerve causes bladder to contract and internal urethral sphincter to mechanically open
  4. Motor neuron causes external sphincter opens when motor neurone is inhibited
  5. Micturition reflex governs bladder emptying in infants
• Nutrient absorption

  1. Occurs in the transport epithelia cells in the small intestine
  2. Glucose is absorbed by secondary active transport by Na⁺-glucose which relies on sodium pump
  3. Sodium pump uses primary active transport to create a sodium gradient where 2K⁺ ions enter the cell and Na⁺ ions leave the cell
  4. Movement of the solutes, sodium, amino acids and glucose create an osmotic gradient