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Renal physiology: Difference between revisions

Revision as of 00:30, 15 July 2016

Renal physiology (Latin rēnēs, "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; clearanceoftoxins; 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.

The mnemonic A WET BED aids in memory of kidneys functions.

A – maintaining ACID-base balance

W – maintaining WATER balance

E – ELECTROLYTE balance

T – TOXIN removal

B – BLOOD Pressure control

E – making ERYTHROPOIETIN

D – Vitamin D metabolism.

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).

Functions of the kidney

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

• Secretion of erythropoietin, which regulates red blood cell production in the bone marrow.
• Secretion of renin, which is a key part of the renin–angiotensin–aldosterone system.
• Secretion of the active form of vitamin D (calcitriol) and prostaglandins.

Gluconeogenesis

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

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

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"^[13] and "nonvolatile acids".^[14] 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 necrosisorglomerular dysfunction.

Mechanisms

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^[15]

Although in the strictest sense of the word excretion with respect to the urinary systemisurination 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.

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 activeorpassive 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⁻isfacilitated out of the cell's basolateral membrane

Hormones

Some key regulatory hormones for reabsorption include:

• aldosterone, which stimulates active sodium reabsorption (and water as a result)
• antidiuretic hormone, which stimulates passive water reabsorption

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.

In nature only a few substances are secreted. These substances are present in great excess, or are natural poisons. But many drugs are cleared by tubular secretion.

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:

Measurement	Calculation	Details
renal plasma flow	${\displaystyle RPF={\frac {\text{effective RPF}}{\text{extraction ratio}}}}$ [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	${\displaystyle RBF={\frac {RPF}{1-HCT}}}$ (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	${\displaystyle GFR={\frac {U_{[{\text{creatinine}}]}\times {\dot {V}}}{P_{[{\text{creatinine}}]}}}}$ (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	${\displaystyle FF={\frac {GFR}{RPF}}}$ [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 diagnosisofmetabolic acidosis
Clearance (other than water)	${\displaystyle C={\frac {U\times {\dot {V}}}{P}}}$ where U = concentration, V =urine volume / time, U*V = urinary excretion, and P = plasma concentration [18]	Rate of removal
free water clearance	${\displaystyle C={\dot {V}}-C_{osm}}$or${\displaystyle {\dot {V}}-{\frac {U_{osm}}{P_{osm}}}{\dot {V}}}$ ${\displaystyle =C_{H_{2}O}}$[19]	The volume of blood plasma that is clearedofsolute-free water per unit time.
Net acid excretion	${\displaystyle NEA={\dot {V}}(U_{NH_{4}}+U_{TA}-U_{HCO_{3}})}$	Net amount of acid excreted in the urine per unit time

References