Regulation of Kidney Function: We know that the removal of wastes from the body is called excretion, and it is done by our excretory system, which comprises a pair of kidneys and a few other organs. But how is its function regulated? How does the kidney know when to excrete dilute urine and when concentrated? Is this regulation related somewhere to blood pressure? Does a regulation involve the function of hormones? If yes, then what are these hormones, and from where these hormones are secreted? One hormone is named renin. Is this renin same as rennin? Get your answers in this article.

Renal physiology is studied at the level of the nephron, the smallest functional unit of the kidney. Each nephron begins with a filtration component that filters the blood that enters the kidney. This filtrate then flows along the length of the nephron, which is a tubular structure lined by a layer of specialised cells and surrounded by capillaries. The major functions of these lining cells are filtration of the blood, reabsorption of water and small molecules, and the discharge of waste from the blood into the urine. Read on to find more!

What is Meant by Regulation of Kidney Function?

The kidneys main function is to excrete wastes from the body. It performs other roles, like regulating blood pressure, acid-base balance, osmoregulation of electrolytes, and endocrine role. In the human body, regulation of Kidney function is very well developed. The regulation of kidneys functioning is under the control of a complex hormonal mechanism as well as the RAAS system and neural regulation. Such a control on the functioning of kidneys is called regulation of Kidney functions.

Components of Machinery Involved in Regulation of Kidney Function

Juxtaglomerular Apparatus

It consists of three types of cells, i.e. Juxtaglomerular cells, Macula densa and Extraglomerular mesangial cells.

a. Juxtaglomerular cells (JGC): Afferent and efferent arteriole consists of swollen smooth muscle cells containing dark granules called juxtaglomerular cells (Juxta-near, glomerular-glomerulus).

i. The granules present in it contain inactive renin.
ii. Renin is an aspartic protease class of an enzyme that is secreted by juxtaglomerular cells of the kidney, which converts blood plasma protein angiotensinogen (secreted from liver) to its active form angiotensin.
iii. JGC is responsible for regulating the function of each nephron by regulating the renal blood flow and glomerular filtration rate.

b. Macula densa- (macula-a spot, densa-dense): Part of the distal convoluted tubule that comes in close proximity to the afferent and efferent arterioles has dense epithelial cells called macula densa.

i. Juxtaglomerular cells along with macula densa form Juxtaglomerular apparatus.
ii. Macula densa functions as chemoreceptors and analyzes the flow of filtrate reaching DCT. If the flow of filtrate reaching DCT is low, it stimulates JGC cells to secrete renin.

c. Extraglomerular mesangial cells or Lacis cells: These are present between afferent and efferent arterioles. It plays a role in regulating GFR.

Fig: Juxtaglomerular Apparatus

What is the Role of and in Regulation of Kidney Function?

The regulation of kidneys functioning is under the control of a complex hormonal mechanism regulated by the Antidiuretic hormone (ADH), Renin-Angiotensin-Aldosterone System (RAAS) and Atrial Natriuretic Factor (ANF). Kidney functions are also auto regulated as well as regulated by the neural system.

Regulation by Antidiuretic hormone (ADH) or Vasopressin: When osmolarity of blood increases, i.e., blood gets hypertonic above 300 mOsm/L, then osmoreceptors present in the brain get stimulated.

• Stimulation of these osmoreceptors cells, in turn, stimulate the hypothalamus, which leads to ADH secretion in the blood from the posterior pituitary lobe.
• ADH promotes the development of aquaporins in the Distal Convoluted Tubule (DCT) and Collecting duct, and thus increases the reabsorption of water.
• Due to the reabsorption of water, the osmolarity of blood starts decreasing, and the urine becomes more concentrated.
• Also, in the hypothalamus, it stimulates thirst centres causing the sensation to drink water and reducing the hypertonicity of blood.
• The decrease in osmolarity of blood and increase in blood pressure results in an increase in GFR.

Why is Vasopressin also known as ADH?

Vasopressin is also known as ADH (Antidiuretic hormone) as it prevents diuresis. Diuresis refers to the production of urine, and this hormone prevents the same by reabsorbing water from kidney tubules.

Regulation by RAAS (Renin-Angiotensin-Aldosterone-System):

1. This system is activated when blood pressure or blood volume, or GFR is low.
2. When GFR is reduced, the amount of filtrate reaching DCT significantly reduces, which is detected by macula densa cells of the distal convoluted tubule (DCT).
3. Macula densa cells, in turn, stimulate specialized smooth muscle cells present in the walls of afferent arterioles called juxtaglomerular cells (JGC cells).
4. This stimulation to JGC cells results in secretion of Renin by Juxtaglomerular cells of the kidneys.
5. Renin then converts blood plasma protein Angiotensinogen (\({\bf{453}}\) amino acids long) to Angiotensin I (10 amino acids peptide).
6. Angiotensin I is converted to Angiotensin II (\({\bf{8}}\) amino acids peptide) in the lungs by Angiotensin-Converting Enzyme (ACE). ACE is a proteolytic enzyme secreted by the lungs.
7. Angiotensin II is a powerful vasoconstrictor that increases blood pressure and Glomerular filtrate rate (GFR).
8. Angiotensin II constricts the efferent arterioles to increase the glomerular blood pressure, which in turn increases GFR.
9. Angiotensin II also stimulates zona glomerulosa of the adrenal cortex, which secretes a hormone called mineralocorticoids or aldosterone.
10. Aldosterone hormone causes reabsorption of sodium ions from the filtrate in convoluted tubules of nephrons which results in osmotic reabsorption of water in the blood, causing an increase in blood volume and thereby increase in GFR.
11. At the same time, there is the excretion of potassium ions into the tubular fluids for maintaining electrolyte balance.
12. Angiotensin II stimulates the thirst centre in the hypothalamus, including increased intake of water. This also increases the volume of blood, followed by an increase in glomerular blood pressure and GFR.
13. Angiotensin II stimulates neurohypophysis to release ADH, which in turn increases reabsorption of water through kidney tubules, causing an increase in the volume of blood.

Fig: RAAS

Regulation by Atrial Natriuretic Factor or ANF: Due to the Renin-Angiotensin-Aldosterone system, there is an increase in blood pressure, glomerular filtration rate and blood volume.

1. The increased blood volume increases the stretchability of the walls of the atrial chamber.
2. This stimulates the atrial wall of the heart to secrete ANF.
3. ANF carries out vasodilation, i.e., dilating the blood vessels and thereby decreasing the blood pressure.
4. It also provides negative feedback inhibition to the hormone renin, angiotensin and ADH, which results in decreasing the GFR.
5. ANF also enhances the excretion of sodium and water by the kidneys.

Fig: Regulation of Kidney Function

Neural regulation: The kidneys are innervated by the vasoconstrictor fibres, the sympathetic division of the autonomic nervous system. Under moderate stimulation by these fibres due to haemorrhage, exercise, fight or flight response, it carries our increased constriction of afferent arterioles. This decreases the GFR and urine formation.

Renal autoregulation:  Renal autoregulation is the ability of the kidneys to maintain constant GFR in spite of changes in systemic arterial pressure. This is brought about by constricting and dilating the afferent arteriole of the nephrons. This helps to compensate for moderate changes in systolic BP for a short duration.

Difference Between Renin and Rennin

Renin	Rennin
It is secreted from the juxtaglomerular cells of the kidneys.	It is secreted by the gastric glands present in the stomach.
It is secreted in active form.	It is secreted in inactive form as prorennin.
It is an enzyme that converts the inactive angiotensinogen to active angiotensin I.	It is a proteolytic enzyme that digests milk protein Casein.
Its secretion is stimulated when there is low GFR or decreased sodium load in tubular fluids.	Its secretion is stimulated by the presence of food in the stomach.

Regulation of Kidney Function: Related Diseases

1. Diabetes Insipidus: Deficiency of ADH causes Diabetes insipidus. This hormone is synthesized by the hypothalamus but is secreted from the posterior pituitary. Due to the under secretion of ADH, a large amount of water is excreted out of the body, and the urine formed is highly dilute. This may occur due to hypothalamic destruction or neurohypophyseal destruction. Symptoms include intense thirst, dilute urine and excessive urination (diuresis).
2. Hypertension due to oversecretion of renin: If renin is secreted from juxtaglomerular cells in large amounts, then there will be more activation of angiotensinogen to angiotensin, which in turn leads to more constriction of blood vessels resulting in hypertension.

Urine Test

Part of the assessment of kidney function includes the measurement of urine and its contents. Too much or too little urine may be produced due to abnormal kidney function. The kidney’s ability to filter protein is often measured as urinary albumin or urine protein levels, either in a single instance or, due to variation throughout the day, with a 24-hour urine test.

Blood Test

Blood tests are also used to assess kidney function. These include tests that aim to directly measure kidney function, as well as tests that assess kidney function by looking for evidence of problems associated with abnormal function. One of the measures of kidney function is the glomerular filtration rate (GFR).

Other tests that can assess kidney function include assessment of electrolyte levels such as potassium and phosphate, assessment of acid-base status by measurement of bicarbonate levels from a vein, and assessment of the complete blood count for anemia.

Glomerular Filtration Rate

Glomerular filtration rate (GFR) describes the amount of fluid filtered from the renal (renal) glomerular capillaries into the Bowman’s capsule per unit time. Creatinine clearance is the amount of blood plasma that is cleared of creatinine per unit time and is a useful measure to estimate GFR. Creatinine clearance exceeds GFR due to creatinine secretion, which can be inhibited by cimetidine.

Both GFR and C-Cr can be accurately calculated or estimated by comparative measurement of substances in blood and urine, by formulas using just one blood test result (EGFR and EC-Cr). The results of these tests assess the excretory function used in kidneys. The staging of chronic kidney disease is based on the categories of GFR as well as leukopenia and kidney disease.

Summary

The kidney is the excretory organ. It performs other roles, too, like regulation of blood pressure, acid-base balance, osmoregulation of electrolytes, and endocrine role too. In the human body, regulation of Kidney function is very well developed. The regulation of kidneys functioning is under the control of a complex hormonal mechanism as well as the RAAS system and neural regulation. Such a control on the functioning of kidneys is called regulation of Kidney functions. The hormonal regulation of Kidney function is under control of Antidiuretic hormone (ADH), Renin-Angiotensin-Aldosterone System (RAAS) and the Atrial Natriuretic Factor (ANF).

FAQs

Q.1. What is the role of ANF in the regulation of kidney function?
Ans: 1. ANF carries out vasodilation, i.e., dilating the blood vessels and thereby decreasing the blood pressure.
2. It also provides negative feedback inhibition to the hormone renin, angiotensin and ADH, which results in decreasing the GFR.
3. ANF also enhances the excretion of sodium and water by the kidneys.

Q.2. How is kidney function regulated?
Ans: The regulation of kidneys functioning is under the control of a complex hormonal mechanism regulated by the Antidiuretic hormone (ADH), Renin-Angiotensin-Aldosterone System (RAAS) and Atrial Natriuretic Factor (ANF). Kidney functions are also auto regulated as well as regulated by the neural system.

Q.3. What is a Juxtaglomerular apparatus?
Ans: It consists of three types of cells:-
a. Juxtaglomerular cells
b. Macula densa
c. Extraglomerular mesangial cells
These cells help in regulating GFR.

Q.4. What does GFR mean?
Ans: GFR refers to the glomerular filtration rate. It is the amount of fluid filtered per unit time from the capillaries of the glomerulus to the Bowman’s capsule.

Q.5. Which cells release renin?
Ans: Juxtaglomerular cells of the kidney release renin.

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