Cells Respond to Their External Environments

Chapter 8

Production of Hormones

How Kidneys Works

Generation of urine during transport along the tubules of kidney Diffusion of small molecules from capillaries to tubules of kidney

through very leaky walls • Filtrate: the fluid in the tubules

Transporters to reabsorb nutrient• Tight junctions and microvilli• Isotonic filtrate: osmotic balance between filtrate and extracellular

fluid Water impermeable, active transport of ions

• Dilute urine Tubule with aquaporin channel and salt channels

• Concentrated urine Bladder

Solute Transport in the Kidney

Regulation of Blood Volume and Salt Balance

Increasing water or sodium reabsorption High blood pressure

Hormonal regulation of blood pressure Regulation of muscle tension in the artery walls

• Angiotensin– Muscle contraction increasing blood pressure

• Atrial natriuretic hormone (ANH)– Relaxation of muscle decreasing blood pressure

Regulation of salt and water balance• Aldosterone

– Increasing retention of salt increase blood volume and pressure• Antidiuretic hormone (ADH)

– Increasing retention of water

Regulation of Angiotensin and ANH

Angiotensin Release via an enzyme cascade

• Secretion of renin in kidney• Renin generate angiotensin I by cleavage of inactive blood

protein• Cleavage of angiotensin I by antiotensin-converting enzyme

(ACE) to form angiotensin II muscle contraction• Conversion of antiotension II to III in kidney stimulation of

aldosterone secretion

The Renin-Angiotensin Cascade

Aldosterone and ADH

Aldosterone Steroid hormone generated by the adrenal gland of the kidneys Binding to receptor

• Increasing Na reabsorption – Increasing the activity of Na channels facing the filtrate– Increasing transcription of Na/K pump on the back of the

epithelium ADH

Small protein secreted from the pituitary gland of brain Binding to receptor on kidney epithelial cells

• Increasing water absoption– Increasing aquaporins (previously stored in vesicles) on the

membrane Suppression of the release of aldosterone and renin Alcohol inhibits ADH release

Signals for hormone release

Osmoreceptors Sensing blood Na concentration High Na release of ADH Low salt Relase of aldosterone

Baroreceptors Sensing blood volume Low blood volume

• Release of ADH, aldosterone, angiotensin

High blood volume• Release of ANH

Responses to Excess Salt

increasing blood volume and pressure

Stretch receptor in the heartRelease of ANH

Relaxation of blood vessels

Activation of osmoreceptors in the hypothalamus

Nerve signal to pituitary to release ADH

Increase in aquaporin channels in the kidney tubules

More water reabsorption

Salt excess

Inhibition of renin and aldosterone secretion

Excretion of more salt

Blood Loss

increasing blood volume and pressure

Activation of baroreceptors in the kidney

release of renin

Increase in angiostnsin and aldosterone

Blood loss

Release of ADH

Failure of Salt and Water Balance

ADH failure Excess urinating up to 16 liters/day Diabetes insipidus Types of problems

• No ADH production • No response to ADH : problems in ADH receptor or

aquaporin

Syndrome of inappropriate ADH (SIADH) Too much ADH production Water retention and low blood sodium concentration

• Brain swelling

Aldosterone Failure

Inactivation of aldosterone pathway Low blood sodium concentration, dehydration No aldosterone production Failure to respond to aldosterone

• Mutation in aldosterone receptor or sodium channel

Activation of aldosterone pathway High blood pressure

• Mutation in an enzyme regulating aldosterone receptor• Mutation in the cytoplasmic domain of the sodium channel

Biotechnology Application

People with high blood pressure: 10 to 30 % Can cause heart disease, stroke, and blindness

Treatment ACE inhibitor

• Inhibition of angiotensin I to II conversion– Lower angiotnesin II lower blood pressure– Lower angiotnesin III lower aldosterone release

Angiotensin receptor blocker Diuretics

• Target salt and water secretion– Blocking aldosterone receptor– Blocking sodium channel