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?

ACTH TSH FSH

Hypoth

Ant. Pit/

Gland

Targets

Actions

Feedback

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 --

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

2

34

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

BP decrease

BP increase

sense

message

mechanism

result

Worksheet