Renal physiology

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

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" and "nonvolatile acids". 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, whose sum is called renal clearance or renal excretion. That is:

Urinary excretion rate = Filtration rate – Reabsorption rate + Secretion rate

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.

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

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: