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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
The posterior pituitary
Hypothalamus
Posteriorpituitary
Hypothalamichormones
Neurosecretorycells of thehypothalamus
Blood vessels
Hormone
Response
ADH Oxytocin
Mammary glands,uterine muscles
Aquaporinsactivated; H2O reabsorbed
Contraction duringlabor; ejection of
milk during nursing
Kidneynephrons
Target
Why might inhibiting ADH lead to lower blood pressure?
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-
55Apical 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
44
221133
1 Na-K-ATPase (3Na out 2K in2 K leak channel (K out)3 Na-K-Cl Triporter (Na, 2Cl, K)4 Cl channel (Cl out)5 Na leak through tight junction
5
Paracellular channel
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
Me
du
lla
Co
rte
x
NephronNephron
Renalartery
Renalvein
Ureter
Bladder
Urethra
In most nephrons,the loop of Henleis relatively shortand is located inthe cortex
In some nephronsthe loop of Henleis long and plungesinto the medulla
The “nephron” is the site of exchange
1
2
34
5
6
7
8
1 Glomerulus + Bowman’s capsule2 Proximal convoluted tubule3 Loop of Henle4 Descending limb5 Ascending limb6 Mucula densa7 Distal convoluted tubule8 Collecting duct
The Nephron
A. Filtration -- Figure in text
B. Reabsorbtion – Figure in text
H2O
H2O
H2O
H2O
H2O
NaCl
NaCl
NaCl
300 mOsM 100
200
400
700
1200
900
600
400
ATP
ADP +P
NaCl H2O
H2O
H2O
H2O
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 --
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
1
2
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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.
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
Renin leads to vasoconstriction via a cascade of hormone signals.
renalrenal
LUNGSLUNGS
Renin
Angiotensinogen Angiotensin I Angiotensin II
Angiotensin Converting Enzyme(ACE)
Vasoconstriction
If you had high blood pressure would you use an ACE inhibitor or an ACE activator? Explain
Angiotensin II acts on many targets
1.Thirst centers of brain2.Decreases baroreceptor reflex (renin release with low P)3.Increases ADH release (ADH release also stimulated by thirst)4.Smooth muscles contraction around arterioles5.Sympathetic NS activity6.Aldosterone release from the adrenal gland
Retain more Na and retain more water.
Reduced Pressure:Renin and ACE leads to vasoconstriction via a cascade of hormone signals.
renalrenalRenin
Angiotensinogen Angiotensin I Angiotensin II
Angiotensin Converting Enzyme(ACE)
Vasoconstriction
ADH
Aldosterone
BP ANF
Heart rate