Glomeruli and Glomerular Filtration Rate (GFR)

The glomeruli are microscopic filters made of a network of capillaries that filter the blood plasma, which occurs in the renal corpuscle of the nephron in the kidneys (figure 1). Glomerular filtration rate (GFR) is defined by amount of blood filtered by the glomerulus into the Bowman’s capsule (ml/per unit of time), the resulting fluid is called the glomerular filtrate. GFR is influenced by the interaction of several important pressures (Khan Academy, 2019).

GFR is determined by the sum of the filtration rates of all the functioning nephrons in the kidneys. As a rough guide, a healthy GFR can be estimated by calculating 140 – [your age] i.e. a healthy 20-year old’s GFR would be 120ml/min. Body weight and height are also considered in the measurement. A GFR of less than 60ml/min can suggest chronic kidney disease (University of Washington, 2019).

GFR can be measured by quantifying the renal clearance of the endogenous substance of creatine, a by-product of muscle metabolism. It is freely filtered by the glomerulus so can be compared to the serum creatine concentration using the following equation:

This however often overestimates GFR due to secretion of creatine by tubules (15%). Instead, an endogenous substance such as inulin (a carbohydrate that is purely filtered by the kidneys as it is neither reabsorbed or secreted) can be used to provide a more accurate measure of GFR. (Traynor, J).

However, inulin is expensive, must be given by intravenous injection and measurements from blood and urine samples must be taken frequently over several hours to obtain an accurate measure of kidney function and filtration (Traynor, J).

The glomerulus is positioned between the afferent arteriole which delivers blood (1-1.1L per minute) to the glomerulus and the efferent arteriole which carries blood away. The efferent arteriole is significantly thinner than the afferent arteriole (figure 3) which maintains a high glomerular capillary pressure required for filtration (University of Washington, 2019).

GFR is directly proportional to the NFP. The hydrostatic pressure must be precisely regulated to maintain efficient filtration. High P_GC can be maintained through an intrinsic process in the kidney called renal autoregulation (figure 4), regardless of natural changes in blood pressure (between 80 and 160mmHg) (University of Washington, 2019). 

Myogenic reflux is a sympathetic response. Baroreceptors in the afferent arterioles detect an increase in blood pressure. This stimulates opening of calcium channels, causing action potential and contraction of the smooth muscle, resulting in vasoconstriction. The volume of blood entering the glomerular capillaries decreases, reducing P_GC and reducing GFR. The opposite occurs when a decrease in blood pressure is detected, to increase GFR (University of Washington, 2019).

The juxtaglomerular apparatus (figure 5) activates the angiotensin-aldosterone system in response to a detecting a decrease in blood pressure.

In response to elevated sodium levels indicating low blood pressure, the macula densa cells stimulate juxtaglomerular cells to secrete the enzyme renin. This activates angiotensinogen (plasma protein in the blood) which is converted to angiotensin I. This is activated by ACE (angiotensin-converting enzyme) and converted to angiotensin II. This is a vasoconstrictor, causing constriction of the afferent arteriole, reducing blood flow and reducing GFR. Blood pressure is increased as it stimulates the thirst centre in the brain, increasing water retention. It also increases cardiac output by increasing stroke volume and heart rate (Histology, Yale. 2018).

ACE inhibitors are used to treat hypertension and lower blood pressure, by preventing the production of angiotensin II. This allows vasodilation of vessels, so they relax and widen, whilst also reducing water retention and blood volume (British Heart Foundation, 2019).

Conversely, the hormone atrial natriuretic peptide (ANP) can increase GFR. An increase in plasma volume activates secretion of the hormone from the heart which causes vasodilation of the afferent arteriole, an increase in sodium excretion (natriuresis) and increase in fluid excretion (diuresis) (University of Washington, 2019). They also decrease the release of renin, preventing the renin-angiotensin system (R, Klabunde. 2019).

References

1. Khan Academy. (2019). Renal physiology: Glomerular filtration. [online] Available at: https://www.khanacademy.org/test-prep/mcat/organ-systems/the-renal-system/a/renal-physiology-glomerular-filtration [Accessed 4 Jan. 2019].
2. University of Washington. (2019). Regulation of GFR. [online] Available at: https://courses.washington.edu/conj/bess/gfr/gfr.htm [Accessed 4 Jan. 2019].
3. Traynor, J. (2006). How to measure renal function in clinical practice. BMJ, 333(7577).
4. Histology, Yale (2019). Juxtaglomerular Apparatus. [online] Available at: http://medcell.med.yale.edu/histology/urinary_system_lab/juxtaglomerular_apparatus.php [Accessed 16 Feb. 2019].
5. British Heart Foundation. (2019). Watch: What are ACE inhibitors and what do they do in your body?. [online] Available at: https://www.bhf.org.uk/informationsupport/heart-matters-magazine/medical/drug-cabinet/ace-inhibitors [Accessed 16 Feb. 2019].
6. Klabunde, R. (2019). CV Physiology | Atrial and Brain Natriuretic Peptides. [online] Cvphysiology.com. Available at: https://www.cvphysiology.com/Blood%20Pressure/BP017 [Accessed 16 Feb. 2019].