68 Glomerular filtration rate (GFR)

After understanding the pivotal role of GFR, it’s crucial to explore the intricate regulatory mechanisms that fine-tune this process. The juxtaglomerular apparatus (JGA) emerges as a central player in this regard, situated near the vascular pole of the renal corpuscle. Comprising juxtaglomerular cells in the afferent arteriole and macula densa cells in the distal convoluted tubule, the JGA orchestrates a mechanism known as tubuloglomerular feedback. This process operates on real-time assessments of sodium chloride concentration within the filtrate by the macula densa cells. When an elevation in sodium chloride is detected, signaling pathways are activated, prompting juxtaglomerular cells to release renin into the bloodstream. Renin triggers a series of events, culminating in the production of angiotensin II, a potent vasoconstrictor. Angiotensin II acts on the afferent arteriole, inducing vasoconstriction to decrease blood flow into the glomerulus and consequently lower GFR. Simultaneously, aldosterone release enhances sodium reabsorption, restoring sodium balance. This intricate feedback loop, orchestrated by the JGA, ensures that GFR remains finely tuned, preventing excessive loss of essential substances and contributing to the stability of internal fluid and electrolyte homeostasis.

GFR is influenced by multiple factors, like those seen at tissue capillary beds (see chapter X). Recall that filtration occurs as pressure forces fluid and solutes through a semipermeable barrier with the solute movement constrained by particle size. Hydrostatic pressure, generated by fluid against a surface, plays a crucial role. Blood in the glomerulus produces glomerular hydrostatic pressure, facilitating fluid movement into the glomerular capsule. Simultaneously, fluid in the capsule exerts pressure, opposing glomerular hydrostatic pressure—known as capsular hydrostatic pressure. These fluids exert pressures in opposing directions. Net fluid movement will be in the direction of the lower pressure. However, the concentration of the solutes in the fluids affects net movement of fluid as well.

Water moves across a membrane from areas of high water concentration (low dissolved solute concentration) to areas of low water concentration (high dissolved solute concentration) through the process of osmosis. The concentration of plasma solutes in the glomerulus is greater than the concentration of the filtrate in the glomerular capsule since the filtration membrane limits the size of particles crossing the membrane. Most proteins cannot pass into the filtrate resulting in water’s movement out of the capsule towards the glomerulus. This pressure acting to draw water into the glomerulus is called blood colloid osmotic pressure. The absence of proteins in the glomerular space (the lumen within the glomerular capsule) results in a capsular osmotic pressure near zero.

Glomerular filtration occurs when glomerular (blood) hydrostatic pressure exceeds the hydrostatic pressure of the glomerular capsule and the blood colloid osmotic pressure. The sum of all of the influences, both osmotic and hydrostatic, results in a net filtration pressure (NFP). Glomerular hydrostatic pressure is typically about 55 mmHg pushing fluid into the glomerular capsule. This outward pressure is countered by a typical capsular hydrostatic pressure of about 15 mmHg and a blood colloid osmotic pressure of 30 mmHg. To calculate the value of NFP:

NFP = Glomerular blood hydrostatic pressure (GBHP) – [capsular hydrostatic pressure (CHP) + blood colloid osmotic pressure (BCOP)] = 10 mm Hg

That is: NFP = GBHP – [CHP + BCOP] = 10 mm Hg

Or: NFP = 55 – [15 + 30] = 10 mm Hg (Figure X.1).

A proper concentration of solutes in the blood is important in maintaining osmotic pressure both in the glomerulus and systemically. There are disorders in which too much protein passes through the filtration slits into the kidney filtrate. This excess protein in the filtrate leads to a deficiency of circulating plasma proteins. Together, blood colloid osmotic pressure decreases, resulting in an increase in urine volume potentially causing dehydration.

As you can see, there is a low net pressure across the filtration membrane. Intuitively, you should realize that minor changes in osmolarity of the blood or changes in capillary blood pressure result in major changes in the amount of filtrate formed at any given point in time. The kidney is able to cope with a wide range of blood pressures. In large part, this is due to the autoregulatory nature of smooth muscle. When you stretch it, it contracts. Thus, when blood pressure goes up, smooth muscle in the afferent arterioles contracts to limit any increase in blood flow and filtration rate. When blood pressure drops, the same capillaries relax to maintain blood flow and filtration rate. The net result is a relatively steady flow of blood into the glomerulus and a relatively steady filtration rate in spite of significant systemic blood pressure changes. Mean arterial blood pressure is calculated by adding 1/3 of the difference between the systolic and diastolic pressures to the diastolic pressure. Therefore, if the blood pressure is 110/80, the difference between systolic and diastolic pressure is 30. One third of this is 10, and when you add this to the diastolic pressure of 80, you arrive at a calculated mean arterial pressure of 90 mm Hg. Therefore, if you use mean arterial pressure for the GBHP in the formula for calculating NFP, you can determine that as long as mean arterial pressure is above approximately 60 mm Hg, the pressure will be adequate to maintain glomerular filtration. Blood pressures below this level will impair renal function and cause systemic disorders that are severe enough to threaten survival. This condition is called shock.

It is vital that the flow of blood through the kidney be at a suitable rate to allow for filtration and yet not too fast to overwhelm the reabsorbing potential of the nephron tubule. This rate determines how much solute is retained or discarded, how much water is retained or discarded, and ultimately, the osmolarity of blood and the blood pressure of the body.

Within the nephron, the tubular reabsorption process is a finely orchestrated mechanism essential for maintaining the body’s fluid and electrolyte balance. As the filtrate, initially produced during glomerular filtration, travels through the renal tubules, specialized cells along the tubule selectively and actively reclaim crucial substances from the filtrate and reintroduce them into the bloodstream.

The glomerulus serves as a highly permeable filter, allowing various substances, including water, sodium, chloride, bicarbonate, glucose, and amino acids, to enter the filtrate. However, to prevent the loss of vital components, tubule cells diligently reabsorb these substances as the filtrate progresses along the nephron. Remarkably efficient, these tubule cells can recover nearly all glucose and amino acids and up to 99% of water and important ions that were initially lost through glomerular filtration. This intricate process ensures that essential elements are returned to the bloodstream, preventing their unnecessary elimination in urine.

As the filtrate embarks on its intricate journey through the nephron, it undergoes dynamic changes in osmolarity, a key determinant of the final composition of urine. This transformation is orchestrated across the distinct segments of the nephron, each playing a specialized role in shaping the osmolarity profile.

The journey commences in the renal corpuscle, where glomerular filtration produces a plasma-like filtrate within the Bowman’s capsule. This initial filtrate closely mirrors the osmolarity of blood plasma, containing essential substances such as water, ions, glucose, and amino acids.

As the filtrate progresses into the proximal convoluted tubule (PCT), a crucial site for tubular reabsorption, water and solutes are selectively reclaimed from the filtrate. The PCT exhibits high permeability, allowing the efficient reabsorption of water, sodium, glucose, and other solutes. This reabsorption process, driven by active and passive transport mechanisms, serves to concentrate the remaining filtrate.

The descending limb of the nephron loop (Loop of Henle) further contributes to changes in osmolarity. As filtrate descends into the hypertonic medullary interstitium, water exits the tubule through osmosis, concentrating the solutes within the tubular fluid.

The ascending limb of the nephron loop plays a pivotal role in maintaining the osmotic gradient. It is impermeable to water but actively transports solutes, primarily sodium and chloride, out of the tubule. This selective solute removal creates a dilute tubular fluid as it ascends towards the renal cortex.

Continuing the journey into the distal convoluted tubule (DCT) and connecting tubule, further fine-tuning of filtrate composition occurs. Here, additional reabsorption and secretion events take place, impacting the osmolarity of the tubular fluid.

Finally, the filtrate reaches the collecting duct, where its osmolarity is fine-tuned based on the body’s hydration status. Antidiuretic hormone (ADH) plays a crucial role in regulating water reabsorption in the collecting duct, adjusting the concentration of the final urine.

In essence, the nephron orchestrates a symphony of osmotic adjustments, dynamically modulating filtrate osmolarity at various segments. This precise regulation ensures that the kidneys can produce urine with osmolarity tailored to maintain fluid balance and respond to the body’s hydration needs.