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Why do we need a kidney?

The primary function of a kidney is water balance, acid-base balance, salt balance, blood pressure regulator and hormone producer (EPO).


What happens with dehydration?

When there is a water deficit, you tend to not lose your salts, the water content goes down, there is an increase in extracellular osmolarity. Osmoreceptors send a signal to increase ADH secretion from the posterior pituitary gland. This will increase the plasma ADH. This will then increase water permeability in the distal tubules and collecting ducts. Which will increase the amount of water reabsorbed back into the blood. Thus it will decrease the amount of water secreted into the urine.


Where does ADH release occur?

Primarily in the hypothalamus.


Describe the input to the osmoreceptors in the hypothalamus?

1. There are neurones (supraoptic and paraventricular nuclei) which sense high osmolality, which will result in the stimulation of ADH release.
2. Inputs to the hypothalamus from the medullary vasomotor center increase ADH release in response to decreased circulating volume.
Both initiate mechanisms that influence the supraoptic and paraventricular ADH secreting neurons.


How do osmoreceptor neurons sense osmolality?

As the osmolality of the fluid outside the neurons change. As the osmolality increases a lot of the fluid goes out of the neuron and vice versa. Osmosensory neurons have an internal framework that are lined up in a vertical way (criss-cross). Overtime the neuron size changes it changes electrical activity inside the cell.


What is ADh released in response to?

1. Increased osmolality - less than a 1% change.
2. Decreased ECF volume - greater than 10% change.

Secretion of ADH in response to increased osmolality has a lower threshold and a higher sensitivity (slope) than the response to decreased extracellular volume.


What is the physiological stimuli to ADH secretion?

1. Increased ECF osmolality (1-2%).
2. Decreased ECF volume (7-10%).


What is the non-physiological stimuli to ADH secretion?

1. Pain, stress.
2. Drugs: narcotics, carbamazepine, vincristine, chlorpropamide, ifosfamide, nicotine, SSRIs.
3. Carcinomas (especially small-cell).
4. Pulmonary disorders.
5. CNS disorders.
6. Alcohol inhibits ADH secretion.


How does ADH act on the kidney?

It binds to the V2 receptor (primarily in the distal tubule), which will lead to aqua-porin channels being inserted into the tubular lumen side of the distal tubule cell. Aquaporins are essentially water channels, so water effectively is reabsorbed back into the kidneys.


Why is ADh important?

Changes in ADH are primarily in ensuring volume status. If ADH levels are low = central and nephrogenic diabetes insipidus.


Describe central diabetes insipidus?

Central is when you are unable to produce ADh even though osmolality is changing. Central is usually caused by head trauma - disrupt the osmoreceptor neurons. It is rarely hereditary and it is treated with ADH analogs.


Describe nephrogenic diabetes insipidus?

Nephrogenic is when you are releasing ADH but you don't have the V2 receptors in the kidney (basically no place for ADH to bind to). ADH levels go up and down but there is no effect to osmolality. It can be caused by certain drugs - commonly lithium. It is less commonly hereditary: congenital defect in V2 receptor or inherited defect in aquaporin-2 channel. It is currently not treatable.


What is a water deprivation test?

Deprive someone of water for a certain amount of time and give an analog of ADH. The one with central DI will have a change in osmolality whereas the one with nephrogenic DI will have no change in osmolality.


What is SIADH?

Syndrome of inappropriate ADH secretion.


What occurs in SIADH?

Plasma ADH levels are higher than normal. The patient retains water inappropriately (has negative free water clearance). Their plasma osmolality is significantly lower than normal. If the patient's water intake is not controlled a hypo-osmolal state can result in possible dire consequences.


What can cause SIADH?

Brain injury or tumour, certain anti-cancer drugs, lung cancer and other cancers.


What are patients "restricted" from doing?

Drinking water - if they drink a lot of water they will keep reabsorbing it.


Where is renin released from?

The juxtaglomerular cells.


What conditions is renin release increased?

1. Decrease in afferent arteriolar pressure.
2. Increase in sympathetic activity.
3. Decrease in macula densa NaCL delivery.


What does renin do?

Renin will convert angiotensinogen to angiotensin 1 (which is converted into angiotensin 2 by ACE).


What does angiotensin 2 do?

It binds to AT1 or AT2 receptors to cause a variety of effects.


What happens when angiotensin 2 binds to AT1 receptors?

1. Increase in aldosterone - vasoconstriction of efferent arteriole.
2. Increase in proximal sodium reabsorption.
3. Increase in thirst.
4. Increase in ADH release (concentrated urine - decrease urine flow).
5. Decrease in RBF, but maintains GFR.


What happens when angiotensin 2 binds to AT2 receptors?

1. Vasodilation.


If the right renal artery becomes abnormally constructed, what will happen to renin secretion by the right kidney and left kidney?

The right kidney will have increased renin secretion because of decreased renal perfusion pressure acting via the infrarenal baroreceptor and decreased NaCl pass the macula densa. This increased secretion will result in elevated systemic arterial angiotensin 2 and elevated arterial blood pressure, both of which will inhibit renin secretion from the left kidney.