Having reviewed the anatomy and microanatomy of the urinary system, now is the time to focus on the physiology. You will discover that different parts of the nephron use filtration, reabsorption, and secretion to produce urine. You will learn how each of these processes works and where they occur along the nephron and collecting ducts. The physiologic goal is to modify the composition of the glomerular filtrate and produce the waste product urine.

Glomerular Filtration Rate (GFR)

The volume of filtrate formed by both kidneys per minute is termed the glomerular filtration rate (GFR). The volume of filtrate produced by the kidneys per day is about 180 L in males and 150 L in females. Ninety-nine percent of this filtrate is returned to the circulation by reabsorption so that only about 1–2 liters of urine are produced per day.

GFR is influenced by the hydrostatic pressure and osmotic pressure on either side of the capillary membrane of the glomerulus. Filtration occurs as pressure forces fluid and solutes through a semipermeable barrier with the solute movement constrained by particle size. Hydrostatic pressure is the pressure produced by a fluid against a surface. If you have a fluid on both sides of a barrier, both fluids exert a pressure in opposing directions. Net fluid movement will be in the direction of the lower pressure.

Osmosis is the movement of solvent (water) across a semipermeable membrane from an area of low solute concentration to an area of high solute concentration in an attempt to balance the concentration on both sides. This creates a pressure, osmotic pressure, which will exist until the solute concentration is the same on both sides of a semipermeable membrane. As long as the concentration differs, water will move.

Glomerular filtration occurs when glomerular hydrostatic pressure exceeds the hydrostatic pressure of Bowman’s space. Osmotic pressure tends to oppose filtration because solute concentration is typically higher in the glomerular capillary. This is because there is a size limitation on the substances that can pass into the filtrate, leading to higher solute concentrations in the blood compared to the filtrate. The sum of all of the influences, both osmotic and hydrostatic, results in a net filtration pressure (NFP) of about 10 mm Hg (Figure 9.9).

A proper concentration of solutes in the blood is important in maintaining osmotic pressure both in the glomerulus and systemically. There are disorders in which too much protein passes through the filtration slits into the kidney filtrate. This excess protein in the filtrate leads to a deficiency of proteins in the blood. Because there is less circulating protein, the osmotic pressure of the blood falls. Less osmotic pressure pulling water into the capillaries tips the balance towards hydrostatic pressure, which tends to push it out of the capillaries. The overall effect is that water is lost from the circulation to interstitial tissues and cells. This “plumps up” the tissues and cells, causing a condition termed systemic edema.

Seeing as up to 180 liters of fluid pass through the nephrons of the kidney per day, it is important that most of that water be reabsorbed, along with the electrolytes and nutrients that also pass into the filtrate. The term “reabsorption” is used because these substances originated in the blood and are returning to the blood, in contrast to the digestive system in which nutrients are absorbed from food. The main functions of the kidney tubules are reabsorption of nutrients, maintenance of homeostasis, and elimination of waste, all of which they accomplish by selective reabsorption of nutrients, electrolytes, and water. This is a brief overview of the mechanisms of reabsorption and the functions of the different parts of the nephron, but if you are interested in more detail please refer to Tubular Reabsorption.

The kidney has some additional functions that won’t be explored in this chapter. These include regulation of electrolytes  and hormone activation and/or release (e.g. vitamin D activation,  release of the hormone erythropoietin for RBC synthesis). For more detail on these topics, refer to  Endocrine regulation of kidneys and  Regulation of fluid volume and electrolytes.

Mechanisms of Reabsorption

You may be wondering how this process of reabsorption occurs. The tubules are lined by a single layer of cells and the luminal side (the side on the inside of tubule, where the filtrate is) contains transport proteins that help to move nutrients via the mechanisms outlined below.

• Active transport: Substances travel against their concentration gradient via a protein “pump” that consumes ATP
  • Example: In the proximal convoluted tubule (PCT), a protein actively transports sodium.
• Facilitated diffusion: Substances follow their concentration gradient using a transport protein to cross the cell membrane. This process does not require energy.
  • Example: Glucose transport in the PCT.
• Simple diffusion: Substances follow their concentration gradient and diffuse across a membrane. In order to do so, their chemical properties need to allow them to cross the cell membrane, therefore they cannot be charged or too large.
  • Example: In parts of the Loop of Henle, urea diffuses across the cell membrane.
• Osmosis: movement of water across the membrane to equalize a concentration gradient of a substance that cannot cross the membrane.
  • Example: Water follows actively pumped ions, like Na+.

The Role of Secretion

In addition to reabsorbing important substances, the nephron also secretes certain substances. These are often waste compounds that the body is removing via excretion in the urine. Examples of such waste components are urea and certain drugs. The nephron also uses secretion to balance the body’s pH, usually by secreting H+ and NH4+ to make the urine more acidic and the body more alkaline.

Functions of Renal Tubules

The following section will outline the function of each part of the nephron. Refer to the figure below for an overview.

Proximal Convoluted Tubule (PCT)

Once the filtrate is filtered into Bowman’s space, the first structure it enters is the PCT. Hence, this is the part of the nephron where the filtrate contains the highest amount of substances that need to be reabsorbed, like water, sodium, glucose, amino acids, small proteins, calcium, potassium, magnesium, and chloride. Hence, there are transport proteins located in the PCT to enable reabsorption of all these substances by the mechanisms outlined previously. This is also where the majority of water reabsorption occurs.

Many parts of the nephron have a role in maintaining pH balance and the PCT is one of them. It does this by reabsorbing bicarbonate (HCO3-), which acts as a buffer to balance blood pH. pH balance in the body is vital, because outside of the narrow normal pH range proteins begin to take on or lose hydrogen ions and lose their shape, and therefore their function. In cases of kidney pathology, one of the signs can be acidemia (blood that is too acidic) because the kidneys are not able to adequately balance the pH.

Loop of Henle (LoH)

The main function of the LoH is to reabsorb water and electrolytes. The loop descends towards or into the medulla, where there is a higher concentration of salt and urea. In the descending limb, water responds to the hyperosmotic environment by leaving the tubule by osmosis. The ascending portion is impermeable to water, so the previously reabsorbed water doesn’t just return to the tubule. Here, electrolytes are actively pumped out to maintain the hyperosmotic environment around the LoH.

Distal Convoluted Tubule (DCT)

After passing through the LoH, the filtrate returns to the cortex and enters the DCT. At this point, 80% of the water in the filtrate has been reabsorbed and the DCT recovers another 10-15%. It also has a role in the reabsorption of sodium, chloride, and calcium.

Collecting Ducts

The collecting ducts are not technically part of the nephron and several nephrons will drain into a single collecting duct. However, they still play an important role in controlling the recovery of water. If the body detects a need to retain water, a hormone called antidiuretic hormone (ADH) will be released, which causes aquaporins (water channels) to be inserted into the membranes of the otherwise water-impermeable collecting duct cells. This allows water to be reabsorbed by facilitated diffusion as the filtrate passes through the hyperosmotic medulla on its way to the renal collecting system.

The collecting ducts also have a role in increasing blood pressure when under the influence of the hormone aldosterone. Aldosterone is formed by a chain of events that begin elsewhere in the kidney. The macula densa is a structure that is located where the LoH returns to the cortex and becomes the DCT. It detects the amount of sodium in the filtrate and if it is low, it begins a cascade of events to increase blood pressure and GFR. This is because in a healthy individual, low sodium in this portion of the nephron is usually due to low renal perfusion. The hormone renin is released, which converts angiotensinogen to angiotensin I, which is then converted to angiotensin II. Angiotensin II acts on the vasculature to cause vasoconstriction and also causes release of aldosterone from the adrenal glands, which sit above the kidneys. Aldosterone increases retention of sodium in the collecting duct. When water passively follows, the result is to increase blood volume and assist in maintaining the blood pressure and perfusion of the kidneys. This complex system is often referred to as the RAAS, short for the renin-angiotensin-aldosterone system.