These notes are intended to accompany lectures in Human Physiology by Dr. Peter King at Francis Marion University, Florence, SC 29502.

The kidneys of vertebrates including humans, evolved with the ability to concentrate urine and excrete a fluid that is higher in salt concentration that other body fluids.
This affords water conservation in a terrestrial habitat.
How does the vertebrate kidney work?
The kidney is basically a tube that comes into close contact with blood vessels and some fluid from the blood diffuses into the tube and passes out of the body.
We will look in detail at the human kidney to understand the process.

What is the main function of the Kidney?

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The functional unit of the human kidney is the nephron. (about 1.3 million in human kidney)
Blood comes into contact with the renal tubule in the Bowman's capsule. Each Bowman's capsule has a network of capillaries (glomerulus) surrounded by the capsule which is the end of the renal tube.
Fluid (ultrafiltrate) passes from the blood to the capsule under hydraulic pressure in a process called glomerula filtration.

More correctly ultrafiltration depends upon ...
1. Net hydrostatic pressure (+)
2. Osmotic pressure (-)
3. Hydraulic permeability (3 layers)
The ultrafiltrate consists of all blood constituents except blood cells and proteins.
Proteins and blood cells are too big to fit through the holes.

Glomerular filtration rate (GFR) is about 125ml per minute or 180 liters per day in humans.
Why don't we dehydrate?
Because most of the water and solutes are reabsorbed (we produce about 1-1.5L of urine).
How much of our blood goes to the kidneys?
About 25% of cardiac output at rest, (25% of 5L/min = 1.25L/min).
About 6% of BMR (basal metabolic rate) used in kidney function!

Filtration fraction = GFR/renal plasma flow = 125/625 = .20 = 20%.

Constant filtering of the blood is vital for the removal of waste products and maintenance of homeostasis.
GFR is maintained at relatively constant by an autoregulation mechanism that alters the vasoconstriction of the afferent arterioles.
The sympathetic nervous system also has some control.

Reabsorption of the ultrafiltrate happens in the renal tubules.
Blood enters the glomerula capsule via the afferent artery and leaves via the effeerent artery.
The efferent artery divides to form the peritubular capillaries (vasa recta), that surround the renal tubule and reabsorb selected molecules and ions.

The renal tubule can be divided into the proximal and distal tubules.
Reabsorption of virtually all organic nutrients and about 60% of ions occurs in proximal tubules.
Distal tubules have some active transport of ions in both directions and react to a number of stimuli controlling blood pH and blood volume.

What is not reabsorbed is excreted in the urine and is called clearance.
Different solutes have different rates of clearance.
Generally 100% of glucose is reabsorbed - but this is limited by the active transport mechanism.
If abnormally high levels are in the blood (170 mg glucose/dL plasma) then some may appear as clearance in the urine (diabetes?).

Between the proximal and distal part of some renal tubules in mammals, including humans is the loop of Henle.
This loop enables urine to achieve osmotic concentrations above that of plasma and conserve water.

The kidney is arranged into an exterior cortex and an interior medulla.
The cortex has an osmolarity gradient set up by active sodium and chloride excretion in the loop of Henle.
Urine is concentrated when the collecting ducts pass through the renal medulla and water is lost due to the high osmolarity of surrounding tissue.

The descending loop is permeable to water and equilibriates with the interstitial fluid.
The thick portion of the ascending loop is impermeable to water and Na⁺ and Cl^- are actively pumped out.
NaCl is responsible for most of the concentration gradient. Urea also plays a role.

Remember, as the ultrafiltrate is moving through the loop of Henle it is not only changing osmolarity but it is also decreasing in volume because the vasa recta is reabsorbing water (and some ions).

The vasa recta walls are permeable to water, Na⁺, Cl^- and urea. Diffusion allows the vasa recta to equilibrate with the osmolarity changes in the renal medulla.
The proteins and cells in blood however create colloidal osmotic pressure and so water is absorbed but some urea and Na⁺, Cl^- are left in the interstitial fluid.

The effect of the active pumping of Na⁺ and Cl^- from the ascending tubule and the vasa recta removal of water but not all the Na⁺ and Cl^- (and urea) create an osmolarity gradient in the renal medulla

The collecting tubule travels through medulla and equilibriates with surrounding tissue thus concentrating urine.
Long loops of Henle establish bigger osmolarity gradients and can increase the urine concentration.
Desert mammals have longer loops of Henle and have extremely concentrated urine (up to 25x blood plasma) to conserve water.

Acid-Base regulation
Blood pH is an important aspect of homeostasis.
Bicarbonate, HCO3^- is an important busser and is generally rabsorbed in the proximal tubule and H⁺ is generaly secreted there
In the distal tubule H⁺ are pumped into the tubule from the blood to help balance pH if necessary.

How is filtration and water conservation controlled in the kidney?

Autoregulation
Constant filtering of the blood is vital for the removal of waste products and maintenance of homeostasis.
GFR is maintained at relatively constant by an autoregulation mechanism that alters the vasoconstriction of the afferent arterioles. Precise mechanism not known.
The sympathetic nervous system also has some control.

Antidiuretic Hormone ADH
Antidiuretic hormone is released by the posterior pituitary in response to high solute concentrations in the blood or low blood volume.
It increases the permeability of the collecting ducts and more water is reabsorbed, and urine is more concentrated. ADH stimulates special pores (aquaporin-2) to be transported to the apical membrane of the collecting ducts. This membrane is normally impermeable to water, inclusion of the ducts allow water molecules to flow through the membrane and then move passively back into the blood.

Renin/angiotensin system.
This involves autoregulation of glomerular filtration.
Low blood pressure in the afferent arterioles (adjacent to granular cells) or low Na+ in macula densa of distal tubules causes release of renin from granular cells.
Collectively these cells make up the juxtaglomerular apparatus.

Angiotensin I is converted to angiotensin II by converting enzyme released by capillary endothelium in lungs.
Angiotensin II causes release of aldosterone from adrenal cortex.

Angiotensin II also acts as a general sytemic vaso constrictor, increasing blood pressure.
Some studies suggest that it has a particular constriction on the efferent arteriole (so increasing glomerular filtration).

Yet another hormone effects water balance.
In response to increased venous pressure in the heart certain atrial cells release atrial natriuretic peptide (hormone) (ANP).
This counteracts angiotensin/aldosterone.
ANP inhibits NaCl reabsorption.
It inhibits renin and aldosterone release.
Results in increased salt and water excretion.

Clinical question

Why do kidney stones form?
Why would someone need dialysis and how does it work?


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This webpage was created by Peter King. Please contact the the author with comments at pking@fmarion.edu.
Last edited July 20, 2010.
http://people.fmarion.edu/pking/humanphys/kidneys.html
copyright Peter King.