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.

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

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 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).

Functions of the kidney[edit]

The functions of the kidney can be divided into three groups: secretion of hormones, gluconeogenesis and extracellular homeostasis of pH and blood components. The nephron is the functional unit of the kidney.

Secretion of hormones[edit]

Gluconeogenesis[edit]

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.[1] Renal gluconeogenesis takes place in the renal cortex. The renal medulla is incapable of producing glucose due to absence of necessary enzymes.[2]

Extracellular homeostasis[edit]

The kidney is responsible for maintaining a balance of the following 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 glycosuria. This is associated with diabetes mellitus.[3] reabsorption (almost 100%) via sodium-glucose transport proteins[4] (apical) and GLUT (basolateral).
Oligopeptides, proteins, and amino acids All are reabsorbed nearly completely.[5] reabsorption
Urea Regulation of osmolality. Varies with ADH[6][7] reabsorption (50%) via passive transport secretion reabsorption in medullary collecting ducts
Sodium Uses Na-H antiport, Na-glucose symport, sodium ion channels (minor)[8] 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)[8] reabsorption reabsorption (thin ascending, thick ascending, Na-K-2Cl symporter) reabsorption (sodium-chloride symporter)
Water Uses aquaporin water channels. See also diuretic. absorbed osmotically along with solutes reabsorption (descending) reabsorption (regulated by ADH, via arginine vasopressin receptor 2)
Bicarbonate Helps maintain acid-base balance.[9] reabsorption (80–90%) [10] reabsorption (thick ascending) [11] 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 reabsorption in response to PTH and ↑ reabsorption with Thiazide Diuretics. [12]
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.[4] Inhibited by parathyroid hormone.
Carboxylate reabsorption (100%[13]) 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"[14] and "nonvolatile acids".[15] 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[edit]

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 renal excretion. That is:

Urinary excretion rate = Filtration rate – Reabsorption rate + Secretion rate[16]

Filtration[edit]

Main article: Renal ultrafiltration

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 convoluted tubule, the loop of Henle, the distal convoluted tubule, and a series of collecting ducts to form urine.

Reabsorption[edit]

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[edit]

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[edit]

Some key regulatory hormones for reabsorption include:

Both hormones exert their effects principally on the collecting ducts.

Secretion[edit]

Main article: Clearance (medicine)

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.

Many drugs are eliminated by tubular secretion. Further reading: Table of medication secreted in kidney

Measurement of renal function[edit]

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 RPF = \frac{\text{effective RPF}}{\text{extraction ratio}} [17] 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 RBF = \frac{RPF}{1 - HCT} (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 GFR = \frac{U_{[\text{creatinine}]}\times \dot{V}}{P_{[\text{creatinine}]}} (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 FF = \frac{GFR}{RPF} [18] 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) C = \frac{U \times \dot{V}}{P} where U = concentration, V =urine volume / time, U*V = urinary excretion, and P = plasma concentration [19] Rate of removal
free water clearance C = \dot{V} - C_{osm} or \dot{V} - \frac{U_{osm}}{P_{osm}}\dot{V} =C_{H_2O}[20] The volume of blood plasma that is cleared of solute-free water per unit time.
Net acid excretion NEA = \dot{V} ( U_{NH_4} + U_{TA} - U_{HCO_3} ) Net amount of acid excreted in the urine per unit time

References[edit]

  1. ^ 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. PMID 20546255.  edit
  2. ^ 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.  edit
  3. ^ Sect. 7, Ch. 6: Characteristics of Proximal Glucose Reabsorption. lib.mcg.edu
  4. ^ a b Sect. 7, Ch. 5: Cotransport (Symport). lib.mcg.edu
  5. ^ Sect. 7, Ch. 6: Proximal Reabsorption of Amino Acids: Site of Reabsorption. lib.mcg.edu
  6. ^ Sect. 7, Ch. 6: Proximal Reabsorption of Urea. lib.mcg.edu
  7. ^ V. Excretion of Organic Molecules. lib.mcg.edu
  8. ^ a b VI. Mechanisms of Salt & Water Reabsorption
  9. ^ Sect. 7, Ch. 6: Proximal Reabsorption of Bicarbonate. lib.mcg.edu
  10. ^ Sect. 7, Ch. 12: Proximal Tubular Reabsorption of Bicarbonate. lib.mcg.edu
  11. ^ Sect. 7, Ch. 12: Bicarbonate Reabsorption, Thick Limb of Henle’s Loop. lib.mcg.edu
  12. ^ en.wikipedia.org/wiki/Distal_convoluted_tubule
  13. ^ Walter F., PhD. Boron. Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. ISBN 1-4160-2328-3.  Page 799
  14. ^ Sect. 7, Ch. 12: Physiological Definition of Acids: Volatile Acid. lib.mcg.edu
  15. ^ Sect. 7, Ch. 12: Nonvolatile Acids. lib.mcg.edu
  16. ^ p 314, Guyton and Hall, Medical Physiology, 11th edition
  17. ^ Sect. 7, Ch. 4: Measurement of Renal Plasma Flow; Renal Clearance of PAH. lib.mcg.edu
  18. ^ Sect. 7, Ch. 4: Filtration Fraction. lib.mcg.edu
  19. ^ IV. Measurement of Renal Function. kumc.edu
  20. ^ Sect. 7, Ch. 8: Free water clearance (CH2O). lib.mcg.edu