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Last time: Introduction to endocrine system and the case study of Diabetes
High
Low
b
insulin
a
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
The posterior pituitary
Hypothalamus
Neurosecretory
cells of the
hypothalamus
Hypothalamic
hormones
Posterior
pituitary
Blood vessels
Hormone
Target
Response
ADH
Oxytocin
Kidney
nephrons
Mammary glands,
uterine muscles
Aquaporins Contraction during
activated; H2O labor; ejection of
reabsorbed milk during nursing
Why might inhibiting ADH lead to lower
blood pressure?
ACTH
Hypoth
Ant. Pit/
Gland
Targets
Actions
Feedback
TSH
FSH
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)
=RTiM
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 Cl1 mM CaCl2 solution -> 2 mOsM -> 2 mEq Ca++ and 2 mEq Cl-
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
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Tight junction
Basolateral membrane
1
2
3
4
5
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
5
3
1
2
Paracellular channel
Interstitial space
Similar cellular mechanisms are at work in renal control of water, electrolytes and waste
Four processes are involved
Filgration
The “nephron” is the site of exchange
Reabsorption
Secretion
Excretion
Cortex
Kidney
Nephron
Nephron
Medulla
Renal
vein
Renal
artery
Ureter
Ureter
Bladder
Urethra
In some nephrons
the loop of Henle
is long and plunges
into the medulla
In most nephrons,
the loop of Henle
is relatively short
and is located in
the cortex
1
2
3
4
5
6
7
8
The Nephron
1
7
2
Glomerulus + Bowman’s capsule
Proximal convoluted tubule
Loop of Henle
Descending limb
Ascending limb
Mucula densa
Distal convoluted tubule
Collecting duct
6
A. Filtration -- Figure in text
B. Reabsorbtion – Figure in text
8
3
4
5
300 mOsM
H2O
100
400
200
ATP
NaCl
H2O
600
400
H2O
H2O
H2O
NaCl
900
ADP +
P
NaCl
700
H2O
H2O
H2O
H2O
NaCl
1200
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 --
Problems of hypertension (high blood pressure)
National blood pressure statistics
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
Juxtaglomerular apparatus:
involved in controlling
filtration rate and blood
pressure via NaCl sensing and
pressure sensing cells.
7
Local regulation via the tuboglomerular feedback loop.
2
6
Systemic regulation via reninangiotensin feedback loop.
8
3
4
5
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
Renin leads to vasoconstriction via a cascade of hormone signals.
LUNGS
Angiotensinogen
renal
Angiotensin Converting Enzyme
(ACE)
Angiotensin I
Angiotensin II
Vasoconstriction
Renin
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 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.
Reduced Pressure:
Renin and ACE leads to vasoconstriction via a cascade of hormone signals.
ANF
BP
Angiotensin Converting Enzyme
(ACE)
Heart rate
Angiotensinogen
renal
Renin
Angiotensin I
Angiotensin II
Vasoconstriction
ADH
Aldosterone
Worksheet
BP decrease
sense
message
mechanism
BP increase
result