Renal physiology

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This illustration demonstrates the normal kidney physiology, including the Proximal Convoluted Tubule (PCT), Loop of Henle, and Distal Convoluted Tubule (DCT). It also includes illustrations showing where some types of diuretics act, and what they do. Renal Diuretics.gif
This illustration demonstrates the normal kidney physiology, including the Proximal Convoluted Tubule (PCT), Loop of Henle, and Distal Convoluted Tubule (DCT). It also includes illustrations showing where some types of diuretics act, and what they do.

Renal physiology (Latin renes, "kidneys") is the study of the physiology of the kidney. This encompasses all functions of the kidney, including maintenance of acid-base balance; regulation of fluid balance; regulation of sodium, potassium, and other electrolytes; clearance of toxins; absorption of glucose, amino acids, and other small molecules; regulation of blood pressure; production of various hormones, such as erythropoietin; and activation of vitamin D.

Contents

Much of renal physiology is studied at the level of the nephron, the smallest functional unit of the kidney. Each nephron begins with a filtration component that filters the blood entering the kidney. This filtrate then flows along the length of the nephron, which is a tubular structure lined by a single layer of specialized cells and surrounded by capillaries. The major functions of these lining cells are the reabsorption of water and small molecules from the filtrate into the blood, and the secretion of wastes from the blood into the urine.

Proper function of the kidney requires that it receives and adequately filters blood. This is performed at the microscopic level by many hundreds of thousands of filtration units called renal corpuscles, each of which is composed of a glomerulus and a Bowman's capsule. A global assessment of renal function is often ascertained by estimating the rate of filtration, called the glomerular filtration rate (GFR).

Formation of urine

Diagram showing the basic physiologic mechanisms of the kidney Physiology of Nephron.png
Diagram showing the basic physiologic mechanisms of the kidney

The kidney's ability to perform many of its functions depends on the three fundamental functions of filtration, reabsorption, and secretion, whose sum is called renal clearance or renal excretion. That is:

Urinary excretion rate = Filtration rate – Reabsorption rate + Secretion rate [1]

Although the strictest sense of the word excretion with respect to the urinary system is urination itself, renal clearance is also conventionally called excretion (for example, in the set term fractional excretion of sodium ).

Filtration

The blood is filtered by nephrons, the functional units of the kidney. Each nephron begins in a renal corpuscle, which is composed of a glomerulus enclosed in a Bowman's capsule. Cells, proteins, and other large molecules are filtered out of the glomerulus by a process of ultrafiltration, leaving an ultrafiltrate that resembles plasma (except that the ultrafiltrate has negligible plasma proteins) to enter Bowman's space. Filtration is driven by Starling forces.

Fluid Flow in the Bowman's Capsule and Glomerulus.svg

The ultrafiltrate is passed through, in turn, the proximal convoluted tubule, the loop of Henle, the distal convoluted tubule, and a series of collecting ducts to form urine.

Reabsorption

Tubular reabsorption is the process by which solutes and water are removed from the tubular fluid and transported into the blood. It is called reabsorption (and not absorption) both because these substances have already been absorbed once (particularly in the intestines) and because the body is reclaiming them from a postglomerular fluid stream that is well on its way to becoming urine (that is, they will soon be lost to the urine unless they are reclaimed).

Reabsorption is a two-step process beginning with the active or passive extraction of substances from the tubule fluid into the renal interstitium (the connective tissue that surrounds the nephrons), and then the transport of these substances from the interstitium into the bloodstream. These transport processes are driven by Starling forces, diffusion, and active transport.

Indirect reabsorption

In some cases, reabsorption is indirect. For example, bicarbonate (HCO3) does not have a transporter, so its reabsorption involves a series of reactions in the tubule lumen and tubular epithelium. It begins with the active secretion of a hydrogen ion (H+) into the tubule fluid via a Na/H exchanger:

  • In the lumen
    • The H+ combines with HCO3 to form carbonic acid (H2CO3)
    • Luminal carbonic anhydrase enzymatically converts H2CO3 into H2O and CO2
    • CO2 freely diffuses into the cell
  • In the epithelial cell
    • Cytoplasmic carbonic anhydrase converts the CO2 and H2O (which is abundant in the cell) into H2CO3
    • H2CO3 readily dissociates into H+ and HCO3
    • HCO3 is facilitated out of the cell's basolateral membrane

Influence of hormones

Some key regulatory hormones for re-absorption include:

Both hormones exert their effects principally on the collecting ducts.

Tubular secretion occurs simultaneously during re-absorption of filtrate. Substances, generally produced by body or the by-products of cell metabolism that can become toxic in high concentration, and some drugs (if taken). These all are secreted into the lumen of renal tubule. Tubular secretion can be either active or passive or co-transport. Substances mainly secreted into renal tubule are; H+, K+, NH3, urea, Creatinine, histamine and drugs like penicillin. Tubular secretion occurs at Proximal Convoluted Tubule (PCT) and Distal Convoluted Tubule (D.C.T); for example, at proximal convoluted tubule, potassium is secreted by means of sodium-potassium pump, hydrogen ion is secreted by means of active transport and co-transport, i.e. anti-porter, and ammonia diffuses into renal tubule.

Other functions

Hormone secretion

The kidneys secrete a variety of hormones, including erythropoietin, calcitriol, and renin. Erythropoietin is released in response to hypoxia (low levels of oxygen at tissue level) in the renal circulation. It stimulates erythropoiesis (production of red blood cells) in the bone marrow. Calcitriol, the activated form of vitamin D, promotes intestinal absorption of calcium and the renal reabsorption of phosphate. Renin is an enzyme which regulates angiotensin and aldosterone levels.

Maintaining homeostasis

The kidney is responsible for maintaining a balance of the following substances:

SubstanceDescription Proximal tubule Loop of Henle Distal tubule Collecting duct
Glucose If glucose is not reabsorbed by the kidney, it appears in the urine, in a condition known as glycosuria. This is associated with diabetes mellitus. [2] reabsorption (almost 100%) via sodium-glucose transport proteins [3] (apical) and GLUT (basolateral).
Oligopeptides, proteins, and amino acids All are reabsorbed nearly completely. [4] reabsorption
Urea Regulation of osmolality. Varies with ADH [5] [6] reabsorption (50%) via passive transport secretionreabsorption in medullary collecting ducts
Sodium Uses Na-H antiport, Na-glucose symport, sodium ion channels (minor) [7] reabsorption (65%, isosmotic)reabsorption (25%, thick ascending, Na-K-2Cl symporter)reabsorption (5%, sodium-chloride symporter)reabsorption (5%, principal cells), stimulated by aldosterone via ENaC
Chloride Usually follows sodium. Active (transcellular) and passive (paracellular) [7] reabsorptionreabsorption (thin ascending, thick ascending, Na-K-2Cl symporter)reabsorption (sodium-chloride symporter)
Water Uses aquaporin water channels. See also diuretic.absorbed osmotically along with solutesreabsorption (descending)reabsorption (regulated by ADH, via arginine vasopressin receptor 2)
Bicarbonate Helps maintain acid-base balance. [8] reabsorption (80–90%) [9] reabsorption (thick ascending) [10] reabsorption (intercalated cells, via band 3 and pendrin)
Protons Uses vacuolar H+ATPase secretion (intercalated cells)
Potassium Varies upon dietary needs.reabsorption (65%)reabsorption (20%, thick ascending, Na-K-2Cl symporter)secretion (common, via Na+/K+-ATPase, increased by aldosterone), or reabsorption (rare, hydrogen potassium ATPase)
Calcium Uses calcium ATPase, sodium-calcium exchanger reabsorptionreabsorption (thick ascending) via passive transport reabsorption in response to PTH and ↑ reabsorption with Thiazide Diuretics.
Magnesium Calcium and magnesium compete, and an excess of one can lead to excretion of the other.reabsorptionreabsorption (thick ascending)reabsorption
Phosphate Excreted as titratable acid.reabsorption (85%) via sodium/phosphate cotransporter. [3] Inhibited by parathyroid hormone.
Carboxylate reabsorption (100% [11] ) via carboxylate transporters.

The body is very sensitive to its pH. Outside the range of pH that is compatible with life, proteins are denatured and digested, enzymes lose their ability to function, and the body is unable to sustain itself. The kidneys maintain acid-base homeostasis by regulating the pH of the blood plasma. Gains and losses of acid and base must be balanced. Acids are divided into "volatile acids" [12] and "nonvolatile acids". [13] See also titratable acid.

The major homeostatic control point for maintaining this stable balance is renal excretion. The kidney is directed to excrete or retain sodium via the action of aldosterone, antidiuretic hormone (ADH, or vasopressin), atrial natriuretic peptide (ANP), and other hormones. Abnormal ranges of the fractional excretion of sodium can imply acute tubular necrosis or glomerular dysfunction.

Acid-base

Two organ systems, the kidneys and lungs, maintain acid-base homeostasis, which is the maintenance of pH around a relatively stable value. The lungs contribute to acid-base homeostasis by regulating carbon dioxide (CO2) concentration. The kidneys have two very important roles in maintaining the acid-base balance: to reabsorb and regenerate bicarbonate from urine, and to excrete hydrogen ions and fixed acids (anions of acids) into urine.

Osmolality

The kidneys help maintain the water and salt level of the body. Any significant rise in plasma osmolality is detected by the hypothalamus, which communicates directly with the posterior pituitary gland. An increase in osmolality causes the gland to secrete antidiuretic hormone (ADH), resulting in water reabsorption by the kidney and an increase in urine concentration. The two factors work together to return the plasma osmolality to its normal levels.

ADH binds to principal cells in the collecting duct that translocate aquaporins to the membrane, allowing water to leave the normally impermeable membrane and be reabsorbed into the body by the vasa recta, thus increasing the plasma volume of the body.

There are two systems that create a hyperosmotic medulla and thus increase the body plasma volume: Urea recycling and the 'single effect.'

Urea is usually excreted as a waste product from the kidneys. However, when plasma blood volume is low and ADH is released the aquaporins that are opened are also permeable to urea. This allows urea to leave the collecting duct into the medulla, creating a hyperosmotic solution that "attracts" water. Urea can then re-enter the nephron and be excreted or recycled again depending on whether ADH is still present or not.

The 'single effect' describes the fact that the ascending thick limb of the loop of Henle is not permeable to water but is permeable to sodium chloride. This allows for a countercurrent exchange system whereby the medulla becomes increasingly concentrated, but at the same time setting up an osmotic gradient for water to follow should the aquaporins of the collecting duct be opened by ADH.

Blood pressure

Although the kidney cannot directly sense blood, long-term regulation of blood pressure predominantly depends upon the kidney. This primarily occurs through maintenance of the extracellular fluid compartment, the size of which depends on the plasma sodium concentration. Renin is the first in a series of important chemical messengers that make up the renin–angiotensin system. Changes in renin ultimately alter the output of this system, principally the hormones angiotensin II and aldosterone. Each hormone acts via multiple mechanisms, but both increase the kidney's absorption of sodium chloride, thereby expanding the extracellular fluid compartment and raising blood pressure. When renin levels are elevated, the concentrations of angiotensin II and aldosterone increase, leading to increased sodium chloride reabsorption, expansion of the extracellular fluid compartment, and an increase in blood pressure. Conversely, when renin levels are low, angiotensin II and aldosterone levels decrease, contracting the extracellular fluid compartment, and decreasing blood pressure.

Glucose formation

The kidney in humans is capable of producing glucose from lactate, glycerol and glutamine. The kidney is responsible for about half of the total gluconeogenesis in fasting humans. The regulation of glucose production in the kidney is achieved by action of insulin, catecholamines and other hormones. [14] Renal gluconeogenesis takes place in the renal cortex. The renal medulla is incapable of producing glucose due to absence of necessary enzymes. [15]

Measurement of renal function

A simple means of estimating renal function is to measure pH, blood urea nitrogen, creatinine, and basic electrolytes (including sodium, potassium, chloride, and bicarbonate). As the kidney is the most important organ in controlling these values, any derangement in these values could suggest renal impairment.

There are several more formal tests and ratios involved in estimating renal function:

MeasurementCalculationDetails
renal plasma flow [16] Volume of blood plasma delivered to the kidney per unit time. PAH clearance is a renal analysis method used to provide an estimate. Approximately 625 ml/min.
renal blood flow (HCT is hematocrit)Volume of blood delivered to the kidney per unit time. In humans, the kidneys together receive roughly 20% of cardiac output, amounting to 1 L/min in a 70-kg adult male.
glomerular filtration rate (estimation using creatinine clearance)Volume of fluid filtered from the renal glomerular capillaries into the Bowman's capsule per unit time. Estimated using inulin. Usually a creatinine clearance test is performed but other markers, such as the plant polysaccharide inulin or radiolabelled EDTA, may be used as well.
filtration fraction [17] Measures portion of renal plasma that is filtered.
anion gap AG = [Na+] − ([Cl] + [HCO3]) Cations minus anions. Excludes K+ (usually), Ca2+, H2PO4. Aids in the differential diagnosis of metabolic acidosis
Clearance (other than water) where U = concentration, V = urine volume / time, = urinary excretion, and P = plasma concentration [18] Rate of removal
free water clearance or [19] The volume of blood plasma that is cleared of solute-free water per unit time.
Net acid excretion Net amount of acid excreted in the urine per unit time

Related Research Articles

<span class="mw-page-title-main">Kidney</span> Organ that filters blood and produces urine in humans

In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and right in the retroperitoneal space, and in adult humans are about 12 centimetres in length. They receive blood from the paired renal arteries; blood exits into the paired renal veins. Each kidney is attached to a ureter, a tube that carries excreted urine to the bladder.

Azotemia is a medical condition characterized by abnormally high levels of nitrogen-containing compounds in the blood. It is largely related to insufficient or dysfunctional filtering of blood by the kidneys. It can lead to uremia and acute kidney injury if not controlled.

<span class="mw-page-title-main">Urinary system</span> Anatomical system consisting of the kidneys, ureters, urinary bladder, and the urethra

The human urinary system, also known as the urinary tract or renal system, consists of the kidneys, ureters, bladder, and the urethra. The purpose of the urinary system is to eliminate waste from the body, regulate blood volume and blood pressure, control levels of electrolytes and metabolites, and regulate blood pH. The urinary tract is the body's drainage system for the eventual removal of urine. The kidneys have an extensive blood supply via the renal arteries which leave the kidneys via the renal vein. Each kidney consists of functional units called nephrons. Following filtration of blood and further processing, wastes exit the kidney via the ureters, tubes made of smooth muscle fibres that propel urine towards the urinary bladder, where it is stored and subsequently expelled through the urethra during urination. The female and male urinary system are very similar, differing only in the length of the urethra.

<span class="mw-page-title-main">Nephron</span> Microscopic structural and functional unit of the kidney

The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure called Bowman's capsule. The renal tubule extends from the capsule. The capsule and tubule are connected and are composed of epithelial cells with a lumen. A healthy adult has 1 to 1.5 million nephrons in each kidney. Blood is filtered as it passes through three layers: the endothelial cells of the capillary wall, its basement membrane, and between the podocyte foot processes of the lining of the capsule. The tubule has adjacent peritubular capillaries that run between the descending and ascending portions of the tubule. As the fluid from the capsule flows down into the tubule, it is processed by the epithelial cells lining the tubule: water is reabsorbed and substances are exchanged ; first with the interstitial fluid outside the tubules, and then into the plasma in the adjacent peritubular capillaries through the endothelial cells lining that capillary. This process regulates the volume of body fluid as well as levels of many body substances. At the end of the tubule, the remaining fluid—urine—exits: it is composed of water, metabolic waste, and toxins.

<span class="mw-page-title-main">Renin–angiotensin system</span> Hormone system

The renin-angiotensin system (RAS), or renin-angiotensin-aldosterone system (RAAS), is a hormone system that regulates blood pressure, fluid, and electrolyte balance, and systemic vascular resistance.

Diuresis is the excretion of urine, especially when excessive (polyuria). The term collectively denotes the physiologic processes underpinning increased urine production by the kidneys during maintenance of fluid balance.

<span class="mw-page-title-main">Aldosterone</span> Mineralocorticoid steroid hormone

Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays a central role in the homeostatic regulation of blood pressure, plasma sodium (Na+), and potassium (K+) levels. It does so primarily by acting on the mineralocorticoid receptors in the distal tubules and collecting ducts of the nephron. It influences the reabsorption of sodium and excretion of potassium (from and into the tubular fluids, respectively) of the kidney, thereby indirectly influencing water retention or loss, blood pressure, and blood volume. When dysregulated, aldosterone is pathogenic and contributes to the development and progression of cardiovascular and kidney disease. Aldosterone has exactly the opposite function of the atrial natriuretic hormone secreted by the heart.

<span class="mw-page-title-main">Collecting duct system</span> Kidney system

The collecting duct system of the kidney consists of a series of tubules and ducts that physically connect nephrons to a minor calyx or directly to the renal pelvis. The collecting duct participates in electrolyte and fluid balance through reabsorption and excretion, processes regulated by the hormones aldosterone and vasopressin.

<span class="mw-page-title-main">Distal convoluted tubule</span> Feature of kidney anatomy

The distal convoluted tubule (DCT) is a portion of kidney nephron between the loop of Henle and the collecting tubule.

<span class="mw-page-title-main">Macula densa</span> A region of juxtaglomerular apparatus in nephron of kidney

In the kidney, the macula densa is an area of closely packed specialized cells lining the wall of the distal tubule where it touches the glomerulus. Specifically, the macula densa is found in the terminal portion of the distal straight tubule, after which the distal convoluted tubule begins.

<span class="mw-page-title-main">Loop diuretic</span> Diuretics that act along the loop of Henle in the kidneys

Loop diuretics are pharmacological agents that primarily inhibit the Na-K-Cl cotransporter located on the luminal membrane of cells along the thick ascending limb of the loop of Henle. They are often used for the treatment of hypertension and edema secondary to congestive heart failure, liver cirrhosis, or chronic kidney disease. While thiazide diuretics are more effective in patients with normal kidney function, loop diuretics are more effective in patients with impaired kidney function.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH), also known as the syndrome of inappropriate antidiuresis (SIAD), is characterized by a physiologically inappropriate release of antidiuretic hormone (ADH) either from the posterior pituitary gland, or an abnormal non-pituitary source. Unsuppressed ADH causes a physiologically inappropriate increase in solute-free water being reabsorbed by the tubules of the kidney to the venous circulation leading to hypotonic hyponatremia.

<span class="mw-page-title-main">Glycosuria</span> Medical condition

Glycosuria is the excretion of glucose into the urine. Ordinarily, urine contains no glucose because the kidneys are able to reabsorb all of the filtered glucose from the tubular fluid back into the bloodstream. Glycosuria is nearly always caused by an elevated blood sugar level, most commonly due to untreated diabetes. Rarely, glycosuria is due to an intrinsic problem with glucose reabsorption within the kidneys, producing a condition termed renal glycosuria. Glycosuria leads to excessive water loss into the urine with resultant dehydration, a process called osmotic diuresis.

<span class="mw-page-title-main">Renal tubular acidosis</span> Higher blood acidity due to failure of the kidneys to fully acidify urine

Renal tubular acidosis (RTA) is a medical condition that involves an accumulation of acid in the body due to a failure of the kidneys to appropriately acidify the urine. In renal physiology, when blood is filtered by the kidney, the filtrate passes through the tubules of the nephron, allowing for exchange of salts, acid equivalents, and other solutes before it drains into the bladder as urine. The metabolic acidosis that results from RTA may be caused either by insufficient secretion of hydrogen ions into the latter portions of the nephron or by failure to reabsorb sufficient bicarbonate ions from the filtrate in the early portion of the nephron. Although a metabolic acidosis also occurs in those with chronic kidney disease, the term RTA is reserved for individuals with poor urinary acidification in otherwise well-functioning kidneys. Several different types of RTA exist, which all have different syndromes and different causes. RTA is usually an incidental finding based on routine blood draws that show abnormal results. Clinically, patients may present with vague symptoms such as dehydration, mental status changes, or delayed growth in adolescents.

<span class="mw-page-title-main">Bartter syndrome</span> Medical condition

Bartter syndrome (BS) is a rare inherited disease characterised by a defect in the thick ascending limb of the loop of Henle, which results in low potassium levels (hypokalemia), increased blood pH (alkalosis), and normal to low blood pressure. There are two types of Bartter syndrome: neonatal and classic. A closely associated disorder, Gitelman syndrome, is milder than both subtypes of Bartter syndrome.

<span class="mw-page-title-main">Reabsorption</span> Part of the function of the kidney

In renal physiology, reabsorption, more specifically tubular reabsorption, is the process by which the nephron removes water and solutes from the tubular fluid (pre-urine) and returns them to the circulating blood. It is called reabsorption (and not absorption) because these substances have already been absorbed once (particularly in the intestines) and the body is reclaiming them from a postglomerular fluid stream that is on its way to becoming urine (that is, they will soon be lost to the urine unless they are reabsorbed from the tubule into the peritubular capillaries. This happens as a result of sodium transport from the lumen into the blood by the Na+/K+ATPase in the basolateral membrane of the epithelial cells. Thus, the glomerular filtrate becomes more concentrated, which is one of the steps in forming urine. Nephrons are divided into five segments, with different segments responsible for reabsorbing different substances. Reabsorption allows many useful solutes (primarily glucose and amino acids), salts and water that have passed through Bowman's capsule, to return to the circulation. These solutes are reabsorbed isotonically, in that the osmotic potential of the fluid leaving the proximal convoluted tubule is the same as that of the initial glomerular filtrate. However, glucose, amino acids, inorganic phosphate, and some other solutes are reabsorbed via secondary active transport through cotransport channels driven by the sodium gradient.

In the physiology of the kidney, tubuloglomerular feedback (TGF) is a feedback system inside the kidneys. Within each nephron, information from the renal tubules is signaled to the glomerulus. Tubuloglomerular feedback is one of several mechanisms the kidney uses to regulate glomerular filtration rate (GFR). It involves the concept of purinergic signaling, in which an increased distal tubular sodium chloride concentration causes a basolateral release of adenosine from the macula densa cells. This initiates a cascade of events that ultimately brings GFR to an appropriate level.

In medicine, the urea-to-creatinine ratio (UCR), known in the United States as BUN-to-creatinine ratio, is the ratio of the blood levels of urea (BUN) (mmol/L) and creatinine (Cr) (μmol/L). BUN only reflects the nitrogen content of urea and urea measurement reflects the whole of the molecule, urea is just over twice BUN. In the United States, both quantities are given in mg/dL The ratio may be used to determine the cause of acute kidney injury or dehydration.

In renal physiology, renal sodium reabsorption refers to the process by which the kidneys, having filtered out waste products from the blood to be excreted as urine, re-absorb sodium ions (Na2+) from the waste. It uses Na-H antiport, Na-glucose symport, sodium ion channels (minor). It is stimulated by angiotensin II and aldosterone, and inhibited by atrial natriuretic peptide.

The rock dove, Columbia livia, has a number of special adaptations for regulating water uptake and loss.

References

  1. p 314, Guyton and Hall, Medical Physiology, 11th edition
  2. Sect. 7, Ch. 6: Characteristics of Proximal Glucose Reabsorption. lib.mcg.edu
  3. 1 2 Sect. 7, Ch. 5: Cotransport (Symport). lib.mcg.edu
  4. Sect. 7, Ch. 6: Proximal Reabsorption of Amino Acids: Site of Reabsorption. lib.mcg.edu
  5. Sect. 7, Ch. 6: Proximal Reabsorption of Urea. lib.mcg.edu
  6. V. Excretion of Organic Molecules. lib.mcg.edu
  7. 1 2 VI. Mechanisms of Salt & Water Reabsorption Archived 2007-02-10 at the Wayback Machine
  8. Sect. 7, Ch. 6: Proximal Reabsorption of Bicarbonate. lib.mcg.edu
  9. Sect. 7, Ch. 12: Proximal Tubular Reabsorption of Bicarbonate. lib.mcg.edu
  10. Sect. 7, Ch. 12: Bicarbonate Reabsorption, Thick Limb of Henle’s Loop. lib.mcg.edu
  11. Walter F., PhD. Boron. Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. ISBN   1-4160-2328-3. Page 799
  12. Sect. 7, Ch. 12: Physiological Definition of Acids: Volatile Acid. lib.mcg.edu
  13. Sect. 7, Ch. 12: Nonvolatile Acids. lib.mcg.edu
  14. Gerich, J. E. (2010). "Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: Therapeutic implications". Diabetic Medicine. 27 (2): 136–142. doi:10.1111/j.1464-5491.2009.02894.x. PMC   4232006 . PMID   20546255.
  15. Gerich, J. E.; Meyer, C.; Woerle, H. J.; Stumvoll, M. (2001). "Renal gluconeogenesis: Its importance in human glucose homeostasis". Diabetes Care. 24 (2): 382–391. doi: 10.2337/diacare.24.2.382 . PMID   11213896.
  16. Sect. 7, Ch. 4: Measurement of Renal Plasma Flow; Renal Clearance of PAH. lib.mcg.edu
  17. Sect. 7, Ch. 4: Filtration Fraction. lib.mcg.edu
  18. IV. Measurement of Renal Function. kumc.edu
  19. Sect. 7, Ch. 8: Free water clearance (). lib.mcg.edu