Urinary

Urine Formation

Results from Glomerular Filtration, Tubular Reabsorption and Tubular Secretion
The rates at which different substances are excreted in the urine represent the sum of three renal processes:
(1) Glomerular filtration.
(2) Reabsorption of substances from the renal tubules into the blood.
(3) Secretion of substances from the blood into the renal tubules.
Expressed mathematically:
Urinary excretion rate = Filtration rate - Reabsorption rate + Secretion rate.

Urine formation begins when a large amount of fluid that is virtually free of protein is filtered from the glomerular capillaries into Bowman’s capsule. Most substances in the plasma, except for proteins, are freely filtered, so that their concentration in the glomerular filtrate in Bowman’s capsule is almost the same as in the plasma. As filtered fluid leaves Bowman’s capsule and passes through the tubules, it is modified by reabsorption of water and specific solutes back into the blood or by secretion of other substances from the peritubular capillaries into the tubules.
Glomerular Filtration
The glomerular capillaries have large pores in their walls, and the layer of Bowman’s capsule in contact with the glomerulus has filtration slits.

Water, together with dissolved solutes (but not proteins), can thus pass from the blood plasma to the inside of the capsule and the nephron tubules. The volume of this filtrate produced by both kidneys per minute is called the glomerular filtration rate (GFR).
Endothelial cells of the glomerular capillaries have large pores (200 to 500 Å in diameter) called fenestrae; thus, the glomerular endothelium is said to be fenestrated. As a result of these large pores, glomerular capillaries are 100 to 400 times more permeable to plasma water and dissolved solutes than are the capillaries of skeletal muscles. Although the pores of glomerular capillaries are large, they are still small enough to prevent the passage of red blood cells, white blood cells, and platelets into the filtrate.
Before the filtrate can enter the interior of the glomerular capsule, it must pass through the capillary pores, the basement membrane (a thin layer of glycoproteins lying immediately outside the endothelial cells), and the inner (visceral) layer of the glomerular capsule. The inner layer of the glomerular capsule is composed of unique cells called podocytes. Each podocyte is shaped somewhat like an octopus, with a bulbous cell body and several thick arms. Each arm has thousands of cytoplasmic extensions known as pedicels, or foot processes. These pedicels interdigitate, like the fingers of clasped hands, as they wrap around the glomerular capillaries. The narrow slits between adjacent pedicels provide the passageways through which filtered molecules must pass to enter the interior of the glomerular capsule.
Although the glomerular capillary pores are apparently large enough to permit the passage of proteins, the fluid that enters the capsular space contains only a small amount of plasma proteins. This relative exclusion of plasma proteins from the filtrate is partially a result of their negative charges, which hinder their passage through the negatively charged glycoproteins in the basement membrane of the capillaries. The large size and negative charges of plasma proteins may also restrict their movement through the filtration slits between pedicels.
It is important to know that:
1. Filterability of Solutes Is Inversely Related to Their Size.
2. Negatively Charged Large Molecules Are Filtered Less Easily Than Positively Charged Molecules of Equal Molecular Size.
The forces that act on the glomerular membrane:
These factors are depending on the glomerular membrane conditions that affect GFR. The other factors are the effects of filtration pressure.
The net filtration pressure represents the sum of the hydrostatic and colloid osmotic forces that either favor or oppose filtration across the glomerular capillaries. These forces include
(1) Hydrostatic pressure inside the glomerular capillaries (glomerular hydrostatic pressure), which promotes filtration.
(2) The hydrostatic pressure in Bowman’s capsule outside the capillaries, which opposes filtration.
(3) The colloid osmotic pressure of the glomerular capillary plasma proteins, which opposes filtration; and
(4) The colloid osmotic pressure of the proteins in Bowman’s capsule, which promotes filtration. (Under normal conditions, the concentration of protein in the glomerular filtrate is so low that the colloid osmotic pressure of the Bowman’s capsule fluid is considered to be zero.


Glomerular Ultrafiltrate
The fluid that enters the glomerular capsule is called ultrafiltrate because it is formed under pressure—the hydrostatic pressure of the blood. This process is similar to the formation of tissue fluid by other capillary beds in the body in response to Starling forces. The force favoring filtration is opposed by a counterforce developed by the hydrostatic pressure of fluid in the glomerular capsule.
Also, since the protein concentration of the tubular fluid is low (less than 2 to 5 mg per 100 ml) compared to that of plasma (6 to 8 g per 100 ml), the greater colloid osmotic pressure of plasma promotes the osmotic return of filtered water. When these opposing forces are subtracted from the hydrostatic pressure of the glomerular capillaries, a net filtration pressure of only about 10 mmHg is obtained.
Because glomerular capillaries are extremely permeable and have an extensive surface area, this modest net filtration pressure produces an extraordinarily large volume of filtrate.
The glomerular filtration rate (GFR) is the volume of filtrate produced by both kidneys per minute. The GFR averages 115 ml per minute in women and 125 ml per minute in men. This is equivalent to 7.5 L per hour or 180 L per day (about 45 gallons)! Since the total blood volume averages about 5.5 L, this means that the total blood volume is filtered into the urinary tubules every 40 minutes. Most of the filtered water must obviously be returned immediately to the vascular system, or a person would literally urinate to death within minutes.

Regulation of Glomerular Filtration Rate

Vasoconstriction or dilation of afferent arterioles affects the rate of blood flow to the glomerulus, and thus affects the glomerular filtration rate. Changes in the diameter of the afferent arterioles
result from both extrinsic regulatory mechanisms (produced by sympathetic nerve innervation), and intrinsic regulatory mechanisms (those within the kidneys, also termed renal autoregulation).These mechanisms are needed to ensure that the GFR will be high enough to allow the kidneys to eliminate wastes and regulate blood pressure, but not so high as to cause excessive water loss.
Sympathetic Nerve Effects
An increase in sympathetic nerve activity, as occurs during the fight-or-flight reaction and exercise, stimulates constriction of afferent arterioles. This helps to preserve blood volume and to divert blood to the muscles and heart. A similar effect occurs during cardiovascular shock, when sympathetic nerve activity stimulates vasoconstriction. The decreased GFR and the resulting decreased rate of urine formation help to compensate for the rapid drop of blood pressure under these circumstances.
Hormonal and Autacoid Control of Renal Circulation:
There are several hormones and autacoids that can influence GFR and renal blood flow. Some of them increase the GFR like Endothelial-derived nitric oxide and Prostaglandins and other decrease the GFR like Endothelin.
Renal Autoregulation
When the direct effect of sympathetic stimulation is experimentally removed, the effect of systemic blood pressure on GFR can be observed. Under these conditions, surprisingly, the GFR remains relatively constant despite changes in mean arterial pressure within a range of 70 to 180 mmHg (normal mean arterial pressure is 100 mmHg). The ability of the kidneys to maintain a relatively constant GFR in the face of fluctuating blood pressures is called renal autoregulation.
Changes in blood supply and the blood pressure (80 to 180) affects the GFR only small degree. The mechanisms are:
1. Tubuloglomerular Feedback in Autoregulation of GFR
Low GFR cause a low flow rate at the juxta-glomerular apparatus (J-G) leading to overabsorrption of Na and Cl in the ascending loop, so low ion concentration at J-G cells lead to:
Dilation of the afferent arteriole.
Release of rinin from J-G leading to the formation of angiotensin 1 and 2 causing efferent arteriolar constriction.


2. Myogenic Autoregulation of Renal Blood Flow and GFR
The ability of individual blood vessels to resist stretching during increased arterial pressure, a phenomenon referred to as the myogenic mechanism. Blood vessels respond to increased wall tension or wall stretch by contraction of the vascular smooth muscle. This help to prevent excessive increases in renal blood flow and GFR when arterial pressure increases.
Other Factors
A high protein intake is known to increase both renal blood flow and GFR 20 to 30 per cent within 1 or 2 hours. The explanation is that the high-protein meal increases the release of amino acids into the blood, which are reabsorbed in the proximal tubule. Because amino acids and sodium are reabsorbed together by the proximal tubules, increased amino acid reabsorption also stimulates sodium reabsorption in the proximal tubules. This decreases sodium delivery to the macula densa, which elicits a tubuloglomerular feedback–mediated decrease in resistance of the afferent arterioles. This raises renal blood flow and GFR. This increased GFR allows sodium excretion to be maintained at a nearly normal level while increasing the excretion of the waste products of protein metabolism, such as urea.
A similar mechanism may also explain the marked increases in renal blood flow and GFR that occur with large increases in blood glucose levels in uncontrolled diabetes mellitus. Because glucose, like some of the amino acids, is also reabsorbed along with sodium in the proximal tubule, increased glucose delivery to the tubules causes them to reabsorb excess sodium along with glucose. This, in turn, decreases delivery of sodium chloride to the macula densa, activating a tubuloglomerular feedback–mediated dilation of the afferent arterioles and subsequent increases in renal blood flow and GFR.