Nephron Function and Glomerular Filtration

• The juxtaglomerular apparatus, a small group of cells, aids in controlling the rate of glomerular filtration.
• Juxtaglomerular cells are in the walls of the afferent and efferent arterioles and can secrete renin.
• Renin, after chemical conversions, can increase arteriole constriction and glomerular hydrostatic pressure, which increases the filtration rate.
• Macula densa, specialized endothelial cells in the distal tubule, detect low sodium concentrations.
• If sodium levels are low, the macula densa signals the afferent arterioles to decrease resistance and the juxtaglomerular cells to increase renin release; both enhance kidney blood flow and increase glomerular filtration rate.

Nephron Function

• Nephrons use three basic processes: glomerular filtration, tubular secretion, and tubular reabsorption.
• Glomerular filtration involves the passage of fluid and small blood components through the glomerulus into the nephron tubule.
• Tubular secretion involves the movement of substances from the blood into the renal tubule.
• Tubular reabsorption involves the movement of substances from the renal tubule back into the vascular system.

Glomerular Filtration

• The glomerulus acts as an ultrafine filter for blood.
• The semipermeable membrane keeps blood cells, proteins, and lipids inside the vessel.
• Hydrostatic pressure from the blood pushes water and smaller plasma components into the tubule, creating the filtrate.
• Damage to the semipermeable membrane leads to the escape of larger plasma components, such as blood cells or protein, into the filtrate.
• Clinical sign of renal damage indicated by blood cells or protein in the urine, since their size prevents reabsorption.
• Approximately 125 mL of fluid is filtered out each minute, totaling 180 L/d.
• Around 99% of filtered fluid returns to the bloodstream, with about 1% (less than 2 L) excreted as urine daily.

Tubular Secretion

• Epithelial cells lining the renal tubule can secrete substances from the blood into the tubular fluid.
• Secretion is an energy-using active transport process.
• Electrolytes, some drugs and drug metabolites, and uric acid are removed from capillaries and secreted into the filtrate.
• Epithelial cells use tubular secretion to maintain acid–base levels by secreting hydrogen ions.

Tubular Reabsorption

• Cells lining the renal tubule reabsorb water and essential substances from the filtrate back into the vascular system.
• About 99% of the water filtered at the glomerulus is reabsorbed.
• Vitamins, glucose, electrolytes, sodium bicarbonate, and sodium chloride are regularly reabsorbed.
• Reabsorption uses transport systems that exchange needed ions for unwanted ones.
• Drugs affecting renal function can overwhelm or interfere with these transport systems, leading to acid–base or electrolyte imbalances.
• The reabsorption process maintains correct extracellular fluid volume and composition.

Maintenance of Volume and Composition of Body Fluids

• Kidneys regulate body fluid composition via hormones by balancing electrolyte levels.
• Body fluid volume is controlled by diluting or concentrating the urine.

Sodium Regulation

• Sodium is a major cation that filters through the glomerulus and enters the renal tubule.
• It is actively reabsorbed in the proximal convoluted tubule to the peritubular capillaries.
• As sodium moves out of the filtrate, chloride ions and water follow by passive diffusion to maintain balances.
• Sodium ions are also reabsorbed via a transport system influenced by carbonic anhydrase.
• Carbonic anhydrase speeds the forming of carbonic acid from carbon dioxide and water.
• Carbonic acid dissociates to form sodium bicarbonate, using a sodium ion from the renal tubule and a free hydrogen ion.
• The hydrogen ion remains in the filtrate, making urine slightly acidic.
• Bicarbonate is stored in the renal tubule as the body’s alkaline reserve, uses as a buffer when the body becomes too acidic.
• The distal convoluted tubule adjusts sodium levels via aldosterone and natriuretic hormone.
• Aldosterone is released in response to high potassium levels, sympathetic stimulation, or angiotensin III.
• Aldosterone stimulates a sodium–potassium exchange pump in the distal tubule cells, reabsorbing sodium and losing potassium.
• Natriuretic hormone decreases sodium reabsorption from the distal tubules, resulting in diluted urine or increased volume.
• Natriuretic hormone is released in response to fluid overload or hemodilution.
• Kidneys return bicarbonate to the body’s circulation; the bicarbonate is stored in the renal tubule as the body’s alkaline reserve for use when the body becomes too acidic and a buffer is needed, helping to maintain the body’s acid–base balance.

Countercurrent Mechanism

• Sodium is further regulated in the medullary nephrons via the countercurrent mechanism in the loop of Henle.
• In the descending loop of Henle, cells are freely permeable to water, and water flows out into the high osmolar tissue surrounding the nephron.
• Sodium is actively reabsorbed into the surrounding peritubular tissue in most nephron areas, but is less permeable in the descending limb of the loop of Henle.
• The filtrate at the end of the descending loop of Henle is concentrated in comparison to the rest of the filtrate.
• The ascending loop of Henle is impermeable to water, trapping water in the tubule.
• Sodium, potassium, and chloride are actively transported out of the tubule via the sodium/potassium/chloride cotransport system.
• The fluid in the ascending loop of Henle becomes hypotonic compared to the hypertonic peritubular tissue.
• Antidiuretic hormone (ADH), produced by the hypothalamus and stored in the posterior pituitary gland, is important for fluid balance.
• ADH is released in response to falling blood volume, sympathetic stimulation, or rising sodium levels (sensed by the hypothalamus).
• If ADH is present at the distal convoluted tubule and the collecting duct, the membrane permeability to water increases.
• Water remaining in the tubule flows into the hypertonic tissue surrounding the loop of Henle, where it is absorbed by peritubular capillaries or reenters the descending loop of Henle.
• Resulting urine is hypertonic and of small volume when ADH is present.
• If ADH is not present, the tubule remains impermeable to water.
• Water trapped in the ascending loop of Henle passes into the collection duct, resulting in hypotonic urine of greater volume.
• This countercurrent mechanism and the influence of the hypothalamus and ADH release allow the body to finely regulate fluid volume by regulating the control of sodium and water.

Chloride Regulation

• Chloride is an important negatively charged ion that helps maintain electrical neutrality with the movement of cations across the cell membrane.
• Chloride is reabsorbed at the second half of the proximal convoluted tubule.
• Chloride is actively reabsorbed in the loop of Henle and distal convoluted tubule, where it promotes the movement of sodium out of the nephron.

Potassium Regulation

• Potassium is a cation vital to nervous system, muscle, and cell membrane function.
• About 65% of filtered potassium is reabsorbed at Bowman’s capsule and the proximal convoluted tubule.
• Another 25% to 30% is reabsorbed in the ascending loop of Henle.
• Fine tuning of potassium levels occurs in the distal convoluted tubule, where aldosterone activates sodium–potassium exchange, leading to potassium loss.
• If potassium levels are very high, sodium retention in exchange for potassium leads to water retention and blood volume dilution, further decreasing potassium concentration.

Calcium Regulation

• Calcium is important in muscle function, blood clotting, bone formation, contraction of cell membranes, and muscle movement
• The absorption of calcium from the gastrointestinal (GI) tract is regulated by vitamin D ingested as part of the diet.
• The vitamin must be activated in the kidneys to a form that will promote calcium absorption.
• Once absorbed from the GI tract, calcium levels are maintained within a tight range by the activity of parathyroid hormone (PTH) and calcitonin.