As with many things in life, fluid volumes within the body must be balanced. Achieving the optimal distribution of molecules, ensuring the availability of electrolytes (especially the universally needed sodium and potassium), maintaining the global acid-base balance and, most importantly to this discussing, regulating fluid balance across the body are the chief the responsibilities of renal physiology. Often categorized as the prominent compo- nent of the urinary system, this regulatory mechanism maintains the chemical and fluidic homeostasis. The renal system achieves this homeostasis through three main functions: excretion, separating organic waste from fluids within the body; elimination, removing waste products from the body into the surrounding environment; and regulation, maintaining consistent volume and solute concentrations of blood plasma. Through these means the urinary system plays an important role creating and sustaining intravascular volume.
The primary actors of the urinary system are the kidneys. The kidneys a pair of organs located on either side of the spine in the abdominal cavity in humans usually between T12 and L3 filter blood by separating water-soluble wastes from the rests of its contents. Beginning the process, blood is received by the kidneys through the renal artery originating along the lateral surface of the abdominal aorta. With a direct connection to the abdominal aorta, the kidneys receive a very large amount of the blood pumped through the system approximately 20-25% of the total cardiac output is directed into the kidneys. Such a large proportion of the total cardiac output emphasizes the significant role filtration plays in cardiovascular regulation.
Once in the kidney, the renal artery divides several times until they are finally capillaries upon whom filtration will act. First the renal artery is divided into a series of segmental arteries that further divide into interlobar arteries. These interlobar arteries supply blood through to the arcuate arteries that lie along the boundary between the cortex and the medulla of the kidney (see Figure 1.7). The acruate arteries divide into cortical radiate arteries (also called interlobular arteries) that then feed into afferent arterioles, which then deliver blood to the capillary beds of individual nephrons, the basic functional and structural unit of the kidney. Each nephron consists of both a renal corpuscle, a spherical structure marking the beginning of the nephron made of a glomerulus and a glomerular capsule, often called Bowmans capsule, and a renal tubule, a long slender tube-shaped structure containing the tubular fluid. Blood from the afferent arterioles is fed through to the glomerulus, a structure of a few dozen intertwining capillaries. Pressure gradients (discussed further on) force water and solutes to be filtered out of the blood and into capsular space.
The filtered product, known as filtrate, exiting the renal corpuscle is similar to protein-free blood plasma. From the capsular space, the filtrate will enter the renal tubule wherein organic materials and nutrients will be recovered, much of the water from the filtrate will be recovered, and transporting the remaining wastes further for eventual discharge. This process ensures that useful substrates present in blood plasma (such as sugars and amino acids) are retained while wastes are separated and transported further for removal. As the filtrate passes through the tubule it is transformed into tubular fluid, which gradually changes its composition until finally becoming urine. A simplified schematic of this process can be seen in Figure 1.8.
Urine, the end product of collected metabolic wastes residing in the blood, is composed of three prominent organic wastes: urea, the most abundant organic waste formed mostly from the breakdown of amino acids; creatinine, the waste product of the high energy compound, creatine phosphate, driving muscular contraction; and uric acid, the waste produced during the recycling of nitrogenous bases from RNA molecules. Each of these waste products can only be removed when dissolved in urine and thus their excretion is accompanied by unavoidable water losses. However, because the kidneys are able to produce urine approximately four times more concentrated than that of blood plasma, the fluid losses are minimized.
Here, as elsewhere, we see the presence of pressure manifest as a mode of action. Two distinct pressure gradients act in this space. The first pressure gradient, formed by the difference in the glomerular and capsule pressures, is a fluid pressure and is similar to those driving the fluids throughout the cardiovascular system. A high-pressured environment is created in the glomerulus by the arrangement of smaller efferent arteries proceeding from larger afferent arteries causing the pressure in the glomerular capillaries beds (~50 mmHg) to be significantly higher than those in typical systemic capillaries (~35 mmHg). Pressure in Bowmans capsule occurs from the resistance caused by the filtrate flowing through the tubule and is typically around 15 mmHg. The second pressure gradient results from an osmotic pressure difference, a phenomenon that occurs in solutions of different concentra- tions. When the osmotic pressure is created by differing concentrations of proteins, this is referred to as oncotic pressure. In this case, the oncotic pressures of the glomerulus and the capsule are caused by the presence and absence of blood plasma proteins, respectively. The combination of these pressures acting across the interface of the glomerulus and the cap- sule produce the driving force pushing the fluid into the capsular space. The rate at which fluid is filtered is known as the glomerular filtration rate (GFR) and can be represented via the Starling equation as
GFR = KF[(PG −PB)−(πG −πB)] (1.18)
where KF is the filtration constant representing the product of hydraulic conductivity over the surface area of the acting glomerular capillaries, PG is the hydrostatic pressure of glomerular capillary, PB is the hydrostatic pressure of Bowmans capsule, πG is the oncotic pressure of the glomerular capillary, and πB is the oncotic pressure of Bowmans capsule.
Glomerular filtration is the crucial first step to all kidney function and therefore its rate must be highly controlled. Were this first step of filtration to fail many adverse conse- quences would follow such as wastes no longer being excreted, pH no longer remaining in balance, and a vital component of blood loss compensation would be unavailable. Three different mechanisms regulate the glomerular filtration rate: autoregulation, hormonal reg- ulation, and autonomic regulation.
Autoregulation works at the level of the kidney and ensures that an adequate filtration rate is maintained regardless of changes in blood pressure and flow. Changes in local blood pressure trigger the arteries, arterioles, and capillaries to respond in kind to maintain a constant flow rate. Recall the fluid flow relationships described above. If a pressure drop were to be initiated, the afferent arteriole would dilate while the efferent arteriole would constrict to counteract its effects. The converse relationship is also true. In so doing, blood flow and glomerular pressure can be kept within a consistent level regardless of systemic blood pressure.
Hormonal regulation of the glomerular filtration rate is regulated via the product of both the renin-angiotensin system (a hormone reaction occurs across the kidneys, liver, and circulatory system) and of natriuretic peptides (hormones produced by atrial and ven- tricular distension). A specialized set of cells in the kidneys, known as juxtaglomerular cells, synthesize the enzyme renin in response to decreased blood pressure at the glomeru- lus (as a result of decreased blood volume, decreased systemic pressure, or blockage of the renal artery), stimulation from sympathetic innervation, or reduced osmotic concen- trations within the tubular fluid. These three phenomena are intimately related and can occur concurrently. In each case they are triggered by pressure or volumetric changes, usually within the vasculature. Renin, having been released into the bloodstream by the juxtaglomerular complex, converts an inactive protein within blood plasma, known as an- giotensinogen into angiotensin I which is then converted into angiotensin II by the aptly named angiotensin-converting enzyme. This final state of the hormone, angiotensin II, affects many aspects of human physiology such as constricting the efferent arteriole in the nephron (increasing glomerular pressures and filtration rates), stimulating aldosterone release from the suprarenal glands (increasing sodium reabsorption in the tubule), and ampli- fies the release of antidiuretic hormone throughout the central nervous system (increasing sympathetic motor tone, initiating peripheral vasoconstriction, and mobilizing the venous reservoir). The combined effect of these responses causes systemic blood volumes and pressures to increase with the release of renin, stabilizing the glomerular filtration rate should a pressure or volume drop occur. If blood volume or pressure were to increase, however, under normal conditions the glomerular filtration rate would increase in response, promoting fluid evacuation.
Finally, autonomic innervation of the kidneys allows for sympathetic activation to over- ride the local autoregulation control previously described. Here sympathetic stimulation has one predominant effect: it will induce vasoconstriction of the afferent arterioles, regardless of all other control. This serves to instantaneously decrease the glomerular filtration rate, allowing fluid to be retained momentarily. Sympathetic activation of this regulatory mechanism stems from acute and significant disturbances of the cardiovascular system such as a massive drop in blood pressure or a heart attack.
These three regulatory functions serve the same end: to optimize the fluid and waste removal rate to ensure a stable physiological environment.