Renal physiology

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This illustration demonstrates the normal kidney physiology. It also includes illustrations showing where some types of diuretics act, and what they do.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Overview

Renal physiology is the study of the physiology of the kidneys.

Functions of the kidney

The functions of the kidney can be divided into two groups: secretion of hormones, and extracellular homeostasis.

Secretion of hormones

Extracellular homeostasis

The kidney is responsible for maintaining a balance of several substances:

Substance Description 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 glucosuria. This is associated with diabetes mellitus.[1]. reabsorption (almost 100%) via sodium-glucose transport proteins[2] (apical) and GLUT (basolateral). - - -
amino acids Almost completely conserved.[3] reabsorption - - -
urea Regulation of osmolality. Varies with ADH[4][5] reabsorption (50%) via passive transport secretion - reabsorption in medullary ducts
sodium Uses Na-H antiport, Na-glucose symport, sodium ion channels (minor)[6] reabsorption (65%, isosmotic) reabsorption (25%, thick ascending, Na-K-2Cl symporter) reabsorption (5%, sodium-chloride symporter) reabsorption (5%, principal cells), stimulated by aldosterone
chloride Usually follows sodium. Active (transcellular) and passive (paracellular)[7] reabsorption reabsorption (thin ascending, thick ascending, Na-K-2Cl symporter) reabsorption (sodium-chloride symporter) -
water Uses aquaporin. See also diuretic. - reabsorption (descending) - reabsorption (with 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 reabsorption reabsorption (thick ascending) via passive transport - -
magnesium Calcium and magnesium compete, and an excess of one can lead to excretion of the other. reabsorption reabsorption (thick ascending) reabsorption -
phosphate Excreted as titratable acid. reabsorption (85%) via sodium/phosphate cotransporter[11]. Inhibited by parathyroid hormone. - - -

The body is very sensitive to its pH level. 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.

Mechanisms

The kidney's ability to perform many of its functions depends on the three fundamental functions of filtration, reabsorption, and secretion.

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.

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

Renal plasma threshold

The renal plasma threshold is the minimum plasma concentration of a substance that results in the excretion of that substance in the urine.

For example, the renal plasma threshold for glucose is 180 to 200 mg per 100 ml. Glycosuria (sugar in urine) results when the plasma glucose concentration reaches and exceeds the renal plasma threshold of glucose. When the plasma glucose concentration is very high, the filtered glucose can saturate the carriers and reach the transport maximum of that molecule. Any amount past the transport maximum will continue through the renal tubules and be excreted in the 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) because these substances have already been absorbed once (particularly in the intestines).

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

Hormones

Some key regulatory hormones for reabsorption include:

Both hormones exert their effects principally on the collecting ducts.

Secretion

Tubular secretion is the transfer of materials from peritubular capillaries to renal tubular lumen. Tubular secretion is caused mainly by active transport.

Usually only a few substances are secreted. These substances are present in great excess, or are natural poisons.

Measurement of renal function

Main article: 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:

Measurement Calculation Details
renal plasma flow [14] Volume of blood plasma delivered to the kidney per unit time. Para-aminohippuric acid (PAH) is a renal analysis tool used to provide an estimate.
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 Starling equation) 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 [15] Measures efficiency of reabsorption.
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, U*V = urinary excretion, and P = plasma concentration [16] Rate of removal
free water clearance or [17][18] 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

References


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