The kidney is an organ with many functions. One of its main functions is the excretion of end-products of metabolism in urine. Knowledge of kidney function and its structure is a key to understanding kidney disorders and their treatment. It is also a springboard for health literacy in this area.
The kidney is one of two bean-shaped organs located in the lateral retroperitoneal space – the compartment between the outer layer of the peritoneum and the muscles and bones of the posterior abdominal wall. There is one kidney on the right and another one on the left. A fibrous capsule surrounds it and separates it from other tissues. The concave or indented surface termed the renal hilus is medial (faces inward). The bowed or convex surface is lateral (faces outward). The outer layer just beneath the capsule is the renal cortex. The deeper inner layer is the renal medulla. The functional units within the cortex and medulla form the parenchyma of the organ. The chief functional unit of the kidney is the nephron, of which there is an average of a million in a single kidney at the time of birth. The blood vessel pattern of the kidney is most unique. The renal interstitium is unique as well.
Nephron Structure and Function
There are two types of nephrons based on their location. Most (85%) are located almost entirely in the renal cortex. They are termed cortical nephrons. The remaining 15% are located near the junction between the cortex and the medulla. They are juxtaglomerular nephrons. The nephron consists of two main parts. They are the renal corpuscle and the renal tubule. The renal corpuscle is where blood filtration occurs. The tubule is the site of processing of the fluid during its conversion into urine.
The renal corpuscle consists of two parts. The first part is the glomerulus – one of the many blood filters of the kidney. It is a tangled cluster of capillaries that arises from an afferent arteriole. The afferent arteriole is the inflow vessel of the nephron. It arises from one of the five main branches of the renal artery after it has subdivided four times within the kidney. Blood which leaves the glomerulus drains into an efferent arteriole. Surrounding the glomerulus is a thin cup-shaped double membrane called Bowman’s capsule. The membrane of Bowman’s capsule eventually becomes the renal tubule of the nephron.
The flow of blood from the afferent arteriole into the glomerulus begins glomerular filtration. It is the passage of the fluid part of blood and its small solutes through small slits in the basement membrane of the capillaries of the glomerulus. The filtrate then passes into Bowman’s capsule. Large molecules (particularly most proteins) and blood cells don’t pass through the filter though because they are too large. The process is much like a tea strainer. It allows brewed tea to pass into the teacup, but not the tea leaves. The name for the fluid that goes it through the filter and enters Bowman’s capsule is glomerular filtrate. Some refer to it as tubular fluid or filtrate. It is, for the most part, plasma with almost no proteins.
The amount of blood that passes through all of the glomeruli of both kidneys per unit of time is the glomerular filtration rate (GFR). In the absence of kidney disease, a normal GFR is between 100 ml/min and 125 ml/min according to most sources. The value is lower though with increasing age due to the loss of nephrons.
After wrapping around most of the surface of the tuft of capillaries the membrane of Bowman’s capsule tapers like a funnel to form the renal tubule. The renal tubule is the part of the nephron that collects and conveys glomerular filtrate during is conversion to urine. It has three segments. In the order of flow through them they are the following:
- Proximal convoluted tubule (proximal tubule)
- Loop of Henle (ascending and descending loops of Henle)
- Distal convoluted tubule (distal tubule)
The proximal convoluted tubule (proximal tubule) is the first part of the tubule to receive filtrate. It is so-named because of its position, multiple folds and coiled course. From its location in the cortex it is where the process of reabsorption begins. The proximal tubule is where the most reabsorption occurs. It reabsorbs roughly 65%-70% of the filtrate and between 50% and 55% of the filtered salt. It also reabsorbs some other substances such as potassium, other electrolytes, glucose, amino acids, fats, vitamins and other nutrients the body needs.
The reabsorption of sodium ions is via active transport with chloride ions following along. The reabsorption of some of the other substances is via a different energy-requiring mechanism. Yet others cross over from the tubule into the blood passively via simple diffusion. Movement of the solutes draws water with them. Thus, the reabsorption of water is via osmosis. The proximal tubule is also the first part of the nephron where secretion begins. Some of the secreted substances include uric acid, bile salts and certain drugs.
The next part of the tubule which joins the proximal tubule is the loop of Henle. It is a U-shaped structure with a descending limb and an ascending limb. Fluid flows down the descending limb which is permeable to water but not salt. Thus, water reabsorption occurs in the descending limb by the process of osmosis. Fluid flows upward through the ascending limb which is permeable to salt but not water. Salt reabsorption occurs by diffusion in the first part of the ascending limb, but is pumped out of the second part via an active transport mechanism.
This arrangement produces a salt concentration gradient in the tubule and in the surrounding tissue of the renal medulla. Because of the selective reabsorption of water in the descending limb the concentration of sodium increases from top to bottom and is greatest at the U point and in the first part of the ascending limb.
The passive and active reabsorption of sodium in the ascending limb dilutes the sodium in the ascending limb, but the active transport in the upper half helps create and maintain a hypertonic renal medulla. It also multiplies the salt concentration gradient in the descending limb of the loop of Henle because the hypertonic medulla drives water reabsorption from it.
The flow of fluid in opposite directions within the loop of Henle is a countercurrent. It, along with how it handles salt and sodium in different parts creates a unique concentration gradient. Thus, the loop of Henle bears the label countercurrent multiplier. The loop of Henle reabsorbs between approximately 35% and 40% of filtered salt.
The next part of the nephron to which the ascending limb of the loop of Henle connects is the distal convoluted tubule (distal tubule). It has a very convoluted course much like the proximal tubule. It reabsorbs approximately 10% of the filtered salt and is under the influence of aldosterone. The distal tubule is also the major site of calcium reabsorption. Passive water reabsorption varies, based on one’s hydration status.
After leaving the distal tubule filtrate enters the collecting duct (collecting tubule). Opinion varies as to whether it is truly a part of the renal tubule. The reasons are several distal tubules connect to one collecting duct which they share, and because it is not a direct extension of Bowman’s capsule. Nevertheless, it is the last part of the nephron, and picks up where the distal tubule leaves off.
Even though less sodium reabsorption occurs in the collecting duct than in the more proximal parts of the nephron the process is under greater regulation here. The regulating agent is the hormone, aldosterone. It controls sodium reabsorption along with potassium secretion which occurs jointly in this segment of the nephron. Between 2% and 3% of filtered sodium reabsorption occurs here.
The most significant process that the collecting duct performs though is water conservation. Its ability to save water relative to the body’s need is largely due to the hypertonicity of the renal medulla relative to the fluid flowing through it. Water conservation occurs as a result of the passive flow of water from the tubule into the salt-rich medulla. But it requires the action of antidiuretic hormone (ADH) to open the floodgates, if you will.
The concentration of solutes in the urine is an indicator of the conservation process. The more water reabsorption the greater the urine concentration and vice versa. A rise in serum osmolality sensed by the hypothalamus is what stimulates the release of ADH.
Kidney Blood Flow
Approximately 20% of the blood the heart pumps out flows through the kidneys. The vessel that directly flows into the kidney is the renal artery. It delivers oxygen and other nutrients to the organ. Within each kidney it divides into 5 segmental arteries. The branching pattern from that point is as follows:
Segmental arteries → interlobar arteries → arcuate arteries → interlobular arteries (cortical radiate arteries) → afferent arterioles → glomerular capillaries → efferent arterioles → peritubular capillaries
Unlike other capillary beds, those that form the glomerulus don’t become venules and then veins. The capillaries of each glomerulus converge to form an efferent arteriole. In essence, the glomerulus is the only normal structure of the body which has an artery carrying blood to it and from it.
The efferent arteriole then divides into peritubular capillaries that surround the renal tubules in the renal cortex and medulla. Those in the renal medulla, known as vasa recta, are long, straight and looped. Because these capillaries surround the renal tubules and are freely permeable to water and solutes they receive the substances the tubules reabsorb and release the substances secreted into the tubules.
Blood flow through the vasa recta in the renal medulla is termed a countercurrent exchange. As the name implies, it complements the countercurrent multiplier and prevents disturbance of the high osmolarity of the renal medulla. Like other capillaries the vasa recta are freely permeable to solutes and water. There is variable diffusion of water and solutes into and out of the vessels at each level of the medulla based on the osmolarity at each level and the U shape of the vessels. The result is minimal dilution of the concentration of fluid between the cells of the medulla as the blood flows through it. This blood flow system does not create the concentration gradient of the renal medulla, but helps sustain it.
Peritubular capillaries don’t just work in conjunction with the renal tubules during the processes of reabsorption, secretion and water conservation. They also provide oxygen and other nutrients to the cells that comprise the various kidney structures. Much of the oxygen usage is for active transport reabsorption and secretion. Like other tissues, the kidney also needs oxygen and other nutrients for general metabolism.
Peritubular capillaries of the cortex and vasa recta eventually converge to form venues which merge to form veins. The names and pattern of convergence of the veins parallels the branching of the arteries described above. Those veins eventually merge into the renal vein. The renal vein feeds into the inferior vena cava which returns blood to the right side of the heart. The right ventricle then pumps it through the lungs for replenishment with oxygen.
Renal blood flow is unique in that the kidney is the only organ with two capillary beds in series between arteries and veins. That arrangement allows the maintenance of a constant flow of blood through and around the nephron in the face of modest-to-moderate fluctuations in systemic blood pressure. The term for this phenomenon is renal autoregulation.
Myogenic renal autoregulation is the simplest and best understood way the kidney maintains a stable blood flow in the face of a rising blood pressure. It works by stretch receptors in the afferent arterioles sending out signals to cause the smooth muscle of the vessel to contract when pressure within it tends to rise. The contraction results in constriction of the vessel to keep its diameter the same or make it smaller so as to prevent blood flow through it from increasing.
Tubuloglomerular feedback is another form of renal autoregulation which is less well-understood. Its proposed mechanisms are as follows.
Increased renal artery pressure causes more fluid and sodium delivery to the macula densa in the distal tubule. A sensor there sends some type of signal that causes constriction of the nearby afferent arteriole, thus preventing an increase in blood flow through it.
A drop-in renal artery blood pressure causes a decrease in sodium delivery to the macula densa. This causes dilation of the afferent arteriole and constriction of the efferent arteriole to maintain filtration pressure. Constriction of the efferent arteriole seems to be the result of the action of angiotensin II resulting from stimulation by renin released from the juxtaglomerular cells. The signal causing dilation of the afferent arterial is not clear.
When systemic blood pressure drops too low the renin-angiotensin-aldosterone system (RAAS) supersedes autoregulation to stabilize blood flow through nephrons. It begins with juxtaglomerular cells secreting renin. Renin in turn activates RAAS which results in its cascade of events. The main stimulus of renin secretion in this setting is either or all of the following:
- baroreceptors in afferent arterioles
- decreased salt concentration detected by cells of the macula densa
- increased sympathetic nerve activity in response to decreased systemic blood pressure and activation of systemic baroreceptors
The Renal Interstitium
A full understanding of renal function requires knowledge of the structure and function of the renal interstitium. It does not just provide structural support for the functional units. It has a key functional role in and of itself. That role is as a medium of exchange between the tubular and vascular elements of the kidney.
The renal interstitium is the space between the glomeruli, tubules, blood vessels and nerves. It is composed of two types of cells and the fluid between them. The two types of cells are fibroblasts and migrant cells of the immune system. Fibroblasts synthesize the collagen which comprises the stroma.
Renal interstitial fluid is the solution that bathes these components. It has major functional significance. The reason is the exchange of solutes and water between the tubules and blood vessels during reabsorption, secretion and water conservation is not a direct exchange from one compartment to the other. Rather, it involves flow across this fluid bridge.
A good analogy is a wet sponge snugly immersed in a basin filled with saline. The saltiness is least near the surface but increases deeper into the sponge. The portions near the surface are like the renal cortex. The deeper portions are akin to the renal medulla. Pores in the sponge are equivalent to the spaces between which the renal tubules and blood vessels pass.
Other Functions of the Kidney
At this point it is apparent that the kidney performs functions other than just the production of urine and excretion of end products of metabolism. Briefly, those already touched upon and others are the following:
- Regulation of the concentration of electrolytes – aldosterone → ↑ sodium reabsorption and ↑ potassium secretion in the distal nephron
- Regulation of the amount of water in the body – aldosterone → ↑ sodium reabsorption with water in various parts of the nephron; ADH → ↑ water reabsorption in the collecting duct
- Maintenance of a water and salt balance – a combination of the above processes
- Regulation of blood pressure – RAAS and the negative feedback loop that turns it off when the BP normalizes
- Calcium homeostasis – ↓ serum calcium → ↑ parathyroid hormone (PTH) → ↑ calcium reabsorption in the distal tubule
- Vitamin D metabolism – from the stimulus of PTH the kidney converts inactive vitamin D to its active form
- Regulation of red blood cell production – hypoxemia or anemia → cortical fibroblasts of the renal interstitium → erythropoietin → stimulation of red blood cell production in the bone marrow
- Maintenance of acid-base balance – mainly by tubular secretion of hydrogen ions and/or increased tubular reabsorption of bicarbonate; a net one molecule of bicarbonate is reabsorbed for every hydrogen ion secreted; the kidney produces new bicarbonate by excreting ammonium
Other than the brain, the kidney is probably the most sophisticated and versatile organ in the body. The kidneys account for less than .2% of the total body weight of an average person. Yet they receive 20% of the total blood flow through the body. The kidney is truly an amazing organ. Perhaps more amazing, is the fact that we have two.