Physiology: Renal Physiology

Renal physiology is often taught as a set of equations and diagrams, yet most confusion comes from mixing up the roles of filtration, reabsorption, and secretion. The kidney does all three at once, continuously, across millions of nephrons. Its job is not simply to “make urine,” but to regulate extracellular fluid volume, osmolality, electrolytes, and acid-base balance while clearing metabolic waste and many drugs.

A useful way to stay oriented is to track any solute through three steps: what is filtered at the glomerulus, what is reabsorbed back to blood, and what is secreted into the tubule. What remains in tubular fluid becomes excretion.

The nephron and the flow of renal processing

Each nephron consists of a glomerulus (a high-pressure capillary tuft) and a tubular system that modifies the filtrate. Blood enters via the afferent arteriole, traverses the glomerular capillaries, and exits through the efferent arteriole, which then forms peritubular capillaries and (for juxtamedullary nephrons) the vasa recta. These downstream capillaries are essential for reclaiming water and solutes and for preserving the medullary concentration gradient.

Tubular segments specialize:

• Proximal tubule: bulk reabsorption of sodium, water, bicarbonate, glucose, amino acids.
• Loop of Henle: generates the medullary gradient; separates salt handling from water handling.
• Distal tubule and collecting duct: fine-tuning of sodium, potassium, water, and acid-base under hormonal control.

Glomerular filtration rate (GFR): what gets filtered and why it matters

GFR is the volume of plasma filtered into Bowman’s space per unit time. It reflects kidney function because filtration is the gateway step for clearing many substances.

Filtration is driven by Starling forces across the glomerular capillary. In simplified form, the net filtration pressure depends on hydrostatic pressure in the glomerular capillary, opposing hydrostatic pressure in Bowman’s space, and opposing oncotic pressure from plasma proteins. The glomerular filtration barrier size-selects and charge-selects: water and small solutes pass readily; cells and most proteins do not.

Clinically, changes in afferent or efferent arteriolar tone alter glomerular capillary pressure and thus GFR. Autoregulatory mechanisms (myogenic response and tubuloglomerular feedback) help stabilize GFR across a range of blood pressures, but severe hypoperfusion, obstruction, or intrinsic glomerular disease can overwhelm these controls.

Filtration, reabsorption, secretion: the mass balance that prevents confusion

For any substance $X$:

• Filtered load: $GFR\times P_X$
• Excretion rate: $U_X\times V$
• Net tubular transport: Excretion minus filtered load

A practical identity is: $$U_X\times V=(GFR\times P_X)-{\text{Reabsorbed}}_X+{\text{Secreted}}_X$$

This prevents a common misconception: a high urine concentration does not necessarily mean high filtration. It may reflect low water excretion, increased secretion, or reduced reabsorption.

Clearance: turning urine measurements into functional insight

Clearance expresses how effectively the kidney removes a substance from plasma. It is defined as: $$C_X=\frac{U_X\times V}{P_X}$$ where $U_X$ is urine concentration, $V$ is urine flow rate, and $P_X$ is plasma concentration.

Interpretation hinges on comparing $C_X$ to GFR:

• If $C_X\approx GFR$, the substance is freely filtered and neither reabsorbed nor secreted.
• If $C_X<GFR$, net reabsorption occurs (or the substance is poorly filtered).
• If $C_X>GFR$, net secretion occurs.

This comparison is the conceptual engine behind many renal questions. For example, glucose at normal plasma levels has clearance near zero because it is filtered then almost completely reabsorbed in the proximal tubule. At high plasma glucose, transporters saturate, reabsorption cannot keep up, and glucose appears in urine.

Estimating GFR in practice

In physiology, an ideal filtration marker is freely filtered and neither reabsorbed nor secreted. In clinical settings, GFR is commonly estimated rather than directly measured, but the principle remains: GFR reflects filtration capacity, not tubular function. Tubular processes can be profoundly abnormal even when GFR is near normal, especially early in disease.

Tubular transport: reabsorption and secretion as regulated decisions

Filtration is relatively nonselective; tubular transport is highly selective.

Proximal reabsorption: bulk handling with tight coupling

The proximal tubule reabsorbs most filtered sodium and water, keeping tubular fluid roughly iso-osmotic to plasma. Sodium reabsorption drives the reabsorption of other solutes through cotransport and exchange mechanisms. Bicarbonate reclamation here is central to acid-base control and depends on carbonic anhydrase activity and hydrogen ion secretion.

Because proximal reabsorption is “bulk,” small changes here can have large downstream effects on volume status and solute delivery to distal segments.

Distal nephron: fine-tuning under hormones

Later segments adjust the final composition of urine:

• Aldosterone increases sodium reabsorption and potassium secretion, primarily in the collecting duct. This supports volume regulation but can promote hypokalemia when excessive.
• Antidiuretic hormone (ADH) increases water permeability in the collecting duct, allowing water reabsorption along the medullary gradient and concentrating urine.
• Changes in distal sodium delivery influence potassium secretion; more sodium delivered distally often increases potassium loss because sodium reabsorption creates an electrical gradient favoring potassium secretion.

Secretion is also a key clearance tool. Many organic acids and bases, including various drugs, are secreted into the tubule, increasing clearance beyond what filtration alone would provide.

Urine concentration and dilution: how the kidney controls water

The kidney can produce dilute urine to eliminate excess water or concentrated urine to conserve it. This flexibility relies on two linked systems:

1. The corticomedullary osmotic gradient, created mainly by the loop of Henle.
2. Variable water permeability of the collecting duct, controlled largely by ADH.

Countercurrent multiplication and the loop of Henle

The loop of Henle separates salt transport from water movement. The descending limb is relatively water-permeable, allowing water to leave into an increasingly hyperosmotic medulla. The thick ascending limb reabsorbs sodium, potassium, and chloride but is relatively impermeable to water. This “diluting segment” raises medullary interstitial osmolality while making tubular fluid more dilute as it ascends.

Repeated along the length of the loop, small transverse differences are multiplied into a large longitudinal gradient.

Countercurrent exchange and the vasa recta

The vasa recta preserves the medullary gradient by passive exchange as blood flows down and back up through the medulla. This minimizes “washout” of solutes while still allowing nutrient delivery and fluid return. If medullary blood flow rises too much, the gradient dissipates and concentrating ability falls.

Urea recycling: supporting the inner medulla

Urea is not just waste. Under ADH influence, urea permeability in parts of the collecting duct increases, allowing urea to contribute to the inner medullary osmolality and enhancing water reabsorption. This is one reason low-protein diets can impair maximal urine concentration.

Renal control of acid-base: reclaiming bicarbonate and excreting acid

Maintaining arterial pH requires both rapid buffering and slower organ-level regulation. The kidneys provide long-term control by reclaiming filtered bicarbonate and generating new bicarbonate while excreting net acid.

Key concepts:

• Bicarbonate reabsorption: Most filtered bicarbonate is reclaimed, especially in the proximal tubule, by secreting $H^{+}$ into the lumen. Filtered bicarbonate is converted to $C{O}_2$ and water, then reformed inside the cell and transported back to blood. The net effect is bicarbonate preservation.
• Net acid excretion: To eliminate acid and add “new” bicarbonate to the body, the kidney excretes $H^{+}$ bound to urinary buffers. The main buffers are phosphate (titratable acid) and ammonia (as $N{H}_4^{+}$).
• Ammoniagenesis: The kidney can increase ammonia production during acidosis, allowing excretion of more $H^{+}$ without pushing urine pH to an extreme. This is a major adaptive response to chronic acid loads.

A common misunderstanding is to equate acidic urine with acidosis. Acidic urine can be an appropriate response that corrects systemic acidosis. The relevant measure is net acid excretion relative to the body’s acid load.

Putting it together: a practical way to reason about renal questions

When confronted with a renal physiology problem, follow a structured checklist:

1. Start with filtration: What is the filtered load ($GFR\times P$)?
2. Compare to excretion: What is in urine ($U\times V$)?
3. Infer tubular handling: Is the substance net reabsorbed or secreted?
4. Consider water handling: Is ADH high or low? Is the medullary gradient intact