1. What you should understand from today: How a cascade of hormonal processes lead to a large (whole body) response How the anterior and posterior pituitary communicate with their targets How feedback mechanisms operate in hormonal control Last time: Introduction to endocrine system and the case study of Diabetes     High Low insulin glucagon

2. The posterior pituitary Hypothalamus Posterior pituitary Hypothalamic hormones Neurosecretory cells of the hypothalamus Blood vessels Hormone Response ADHOxytocin Mammary glands, uterine muscles Aquaporins activated; H 2 O reabsorbed Contraction during labor; ejection of milk during nursing Kidney nephrons Target Why might inhibiting ADH lead to lower blood pressure?

3. ACTHTSHFSH Hypoth Ant. Pit/ Gland Targets Actions Feedback

4. Life Aquatic: some simple definitions Osmolarity (Osmol/L or OsM) = molarity of A x number of particles A dissociates into + molarity of B x number of particles B dissociates into + molarity of C x number of particles C dissociates into + … Osmolarity of a 1 M glucose solution? 0.5 M NaCl solution? 0.5 M albumin solution? Osmotic pressure (π) = R T i M R = universal gas constant =0.08206 L · atm · mol -1 · K -1 ; T in K; M = molarity NaCli = 1 1 mM NaCl solution -> 2 mOsM -> 1 mEq Na + and 1 mEq Cl - 1 mM CaCl 2 solution -> 2 mOsM -> 2 mEq Ca ++ and 2 mEq Cl -

5. 5 5 Apical membrane Basolateral membrane Tight junction How do they eliminate the salt? Salmon pump Na and Cl from body fluids into the sea: “chloride cells” in the gill epithelium. Interstitial space Ocean 4 4 2 2 1 1 3 3 1Na-K-ATPase (3Na out 2K in 2K leak channel (K out) 3Na-K-Cl Triporter (Na, 2Cl, K) 4Cl channel (Cl out) 5Na leak through tight junction 5 Paracellular channel

6. Similar cellular mechanisms are at work in renal control of water, electrolytes and waste Four processes are involved Filgration Reabsorption Secretion Excretion Ureter Kidney Cortex Medulla Cortex Nephron Renal artery Renal vein Ureter Bladder Urethra In most nephrons, the loop of Henle is relatively short and is located in the cortex In some nephrons the loop of Henle is long and plunges into the medulla The “nephron” is the site of exchange

7. 1 2 3 4 5 6 7 8 1Glomerulus + Bowman’s capsule 2Proximal convoluted tubule 3Loop of Henle 4Descending limb 5Ascending limb 6Mucula densa 7Distal convoluted tubule 8Collecting duct The Nephron A. Filtration -- Figure in text B. Reabsorbtion – Figure in text

8. H2OH2O H2OH2O H2OH2O H2OH2O H2OH2O NaCl 300 mOsM100 200 400 700 1200 900 600 400 ATP ADP + P NaCl H2OH2O H2OH2O H2OH2O H2OH2O

9. Aquaporins are added to the lumenal membrane of the collecting duct when ADH is present (via cAMP induced exocytosis). Absence of ADH leads to reduced aquaporin numbers (endocytosis). Alcohol inhibits ADH --

10. Problems of hypertension (high blood pressure) National blood pressure statistics

11. Determinants of blood pressure: PA – PV = CO * Resistance (R) CO = Heart Rate (HR) x Stroke Volume (SV) Increase SV via increased sympathetic activation of ventricular muscle Greater blood volume leads to higher pressure Blood volume is determined by renal function Pressure sensors lie in the major vessels serving cranial circulation

12. 1 2 3 4 5 6 7 8 Juxtaglomerular apparatus: involved in controlling filtration rate and blood pressure via NaCl sensing and pressure sensing cells. Local regulation via the tubo- glomerular feedback loop. Systemic regulation via renin- angiotensin feedback loop.

13. Granular cells: Release renin in response to reduced pressure Glomerulus DCT Juxtaglomerular apparatus Macula densa: High NaCl -> stretch activated channels lead to release of paracrine vasopressor (vasoconstrictor). Low NaCl induce renin release KEY: RENIN RELEASE WITH LOW PRESSURE

14. Renin leads to vasoconstriction via a cascade of hormone signals. renal LUNGS Renin AngiotensinogenAngiotensin IAngiotensin II Angiotensin Converting Enzyme (ACE) Vasoconstriction If you had high blood pressure would you use an ACE inhibitor or an ACE activator? Explain

15. Angiotensin II acts on many targets 1.Thirst centers of brain 2.Decreases baroreceptor reflex (renin release with low P) 3.Increases ADH release (ADH release also stimulated by thirst) 4.Smooth muscles contraction around arterioles 5.Sympathetic NS activity 6.Aldosterone release from the adrenal gland Retain more Na and retain more water.

16. Reduced Pressure: Renin and ACE leads to vasoconstriction via a cascade of hormone signals. renal Renin AngiotensinogenAngiotensin IAngiotensin II Angiotensin Converting Enzyme (ACE) Vasoconstriction ADH Aldosterone BP ANF Heart rate

17. BP decrease BP increase sense message mechanism result Worksheet