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What you should understand from today:

Last time: Introduction to endocrine system and the case study of Diabetes. High. b. insulin. a. Low. glucagon. What you should understand from today: How a cascade of hormonal processes lead to a large (whole body) response

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What you should understand from today:

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  1. Last time: Introduction to endocrine system and the case study of Diabetes High b insulin a Low glucagon 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

  2. The posterior pituitary Hypothalamus Neurosecretory cells of the hypothalamus Hypothalamic hormones Posterior pituitary Blood vessels Hormone ADH Oxytocin Kidney nephrons Mammary glands, uterine muscles Target Response Aquaporins activated; H2O reabsorbed Contraction during labor; ejection of milk during nursing Why might inhibiting ADH lead to lower blood pressure?

  3. 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 NaCl i = 1 1 mM NaCl solution -> 2 mOsM -> 1 mEq Na+ and 1 mEq Cl- 1 mM CaCl2 solution -> 2 mOsM -> 2 mEq Ca++ and 2 mEq Cl-

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

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

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

  7. 300 mOsM 100 H2O 400 200 ATP ADP + P NaCl H2O 600 400 H2O NaCl NaCl H2O H2O H2O 900 700 NaCl H2O 1200 H2O H2O

  8. 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 --

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

  10. 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

  11. 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. 1 7 2 6 8 4 3 5

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

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

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

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

  16. Worksheet BP decrease sense message mechanism BP increase result

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