Mechanism of Urine Formation and Osmoregulation

Urine Formation Introduction

Urine formation is a blood-cleansing function. Normally, about 26% of cardiac output enters the kidneys to get rid of unwanted substances.

• Kidneys excrete unwanted substances along with water as urine.
• The unwanted substances include metabolic end products and those substances, which are present in excess quantities in the body.
• Normally, about 1-5 liters of urine is formed every day. The mechanism of urine formation includes several processes.

Read And Learn More: Medical Physiology Notes

• First, when blood passes through the glomerular capillaries, the plasma is filtered into the Bowman’s capsule. This process is called glomerular filtration.
• When the filtrate from Bowman’s capsule passes through the tubular portion of the nephron, it undergoes various changes both in quality and quantity.
• Many wanted substances like glucose, amino acids, water, and electrolytes are reabsorbed from the tubules.
• This process is called tubular reabsorption.
• And, some unwanted substances are secreted into the tubule from peritubular blood vessels.

This process is called tubular secretion or excretion.

Thus, urine formation includes three processes:

1. Glomerular filtration
2. Tubular reabsorption
3. Tubular secretion.

Among these three processes filtration is the function of the glomerulus.

Reabsorption and secretion are the functions of the tubular portion of the nephron.

Glomerular Filtration

Glomerular filtration Introduction

• Glomerular filtration is the process by which the blood that passes through glomerular capillaries is filtered through the filtration membrane.
• Glomerular filtration is the first process of urine formation.

Filtration Membrane

The filtration membrane is formed by three layers:

1. The glomerular capillary membrane
2. Basement membrane
3. Visceral layer of Bowman’s capsule.

1. Glomerular Capillary Membrane

The glomerular capillary membrane is formed by a single layer of endothelial cells which are attached to the basement membrane.

The capillary membrane has many pores called fenestra or filtration pores with a diameter of 0.1 p.

2. Basement Membrane

The basement membrane of glomerular capillaries fuses with the basement membrane of the visceral layer of Bowman’s capsule.

Thus, the basement membranes, which are fused together, form the separation between the glomerular capillary endothelium and the epithelium of the visceral layer of Bowman’s capsule.

3. Visceral Layer of Bowman’s Capsule

This is composed of a single layer of flattened, epithelial cells resting on a basement membrane. Each cell is connected to the basement membrane by cytoplasmic extensions called pedicles or feet.

The pedicles are arranged in an interdigitating manner leaving small cleft-like spaces in between. The cleft-like space is called a slit pore. The epithelial cells with pedicles are called podocytes.

Process of Glomerular Filtration

• When the blood passes through the glomerular capillaries, the plasma is filtered into the Bowman’s capsule.
• All the substances of plasma are filtered except the plasma proteins. The filtered fluid is called glomerular filtrate.

Ultrafsltication

• The glomes-filtration is called ultrafiltration because even the minute particles are filtered. But, the plasma proteins are not filtered due to their large molecular size.
• The protein molecules are larger than the slit pores present in the endothelium of capillaries. Thus, the glomerular filtrate contains all the substances present in plasma except the plasma proteins.

Method Of Collection Of Glomerular Filtrate

• The glomerular filtrate is collected in experimental animals by the micropuncture technique.
• This technique involves the insertion of a micropipette into the Bowman’s capsule and the aspiration of filtrate.

Glomerular Filtration Rate (GFR)

• Glomerular filtration rate (GFR) is defined as the total quantity of filtrate formed in all the nephrons of both kidneys in the given unit of time.
• The normal GFR is 125 mL per minute or about 180 liters per day.

Filtration Fraction

Filtration fraction is the fraction (portion) of the renal plasma which becomes the filtrate. It is the ratio between renal plasma flow and glomerular filtration rate. It is expressed in percentage.

The normal filtration fraction varies from 15-20%.

Pressures Determining Filtration

The pressures, which determine the GFR are:

1. Glomerular capillary pressure
2. Colloidal osmotic pressure in the glomeruli
3. Hydrostatic pressure in the Bowman’s capsule. These pressures determine the GFR by either favoring or opposing the filtration.

1. Glomerular Capillary Pressure

It is the pressure exerted by the blood in glomerular capillaries. It is about 60 mm Hg and, varies between 45 and 70 mm Hg.

Glomerular capillary pressure is the highest capillary pressure in the body. This pressure favors glomerular filtration.

2. Colloidal Osmotic Pressure

• Colloidal Osmotic Pressure is exerted by plasma proteins in the glomerular The plasma proteins are not filtered through the glomerular capillaries and remain in the glomerular capillaries.
• These proteins develop the colloidal osmotic pressure which is about 25 mm Hg. It opposes glomerular filtration.

3. Hydrostatic Pressure in Bowman’s Capsule

Hydrostatic Pressure in Bowman’s Capsule is the pressure exerted by the filtrate in Bowman’s capsule. It is also called capsular pressure. It is about 15 mm Hg. It also opposes glomerular filtration.

Net Filtration Pressure

• Net filtration pressure is the balance between pressure favoring filtration and pressures opposing filtration.
• Net Filtration Pressure is otherwise known as effective filtration pressure or essential filtration pressure. It is very essential for the maintenance of GFR.

The net filtration pressure =

The normal net filtration pressure is about 20 mm Hg, and, it varies between 15 and 20 mm Hg.

Starling’s Hypothesis and Starling Forces

• The determination of net filtration pressure is based on Starling’s hypothesis.
• Starling’s hypothesis states that the net filtration through the capillary membrane is proportional to the hydrostatic pressure difference across the membrane minus the oncotic pressure difference.
• The hydrostatic pressure within the glomerular capillaries is the glomerular capillary pressure.
• All the pressures involved in the determination of filtration are called Starling forces.

Filtration Coefficient

• The filtration coefficient is the GFR in terms of net filtration pressure, it Is the GFR per mm Hg of net filtration pressure.
• For example, when GFR is 125 mL/min and Turnon pressure is 20 mm Hg.
• The Filtration coefficient =125ml/20mmhg=6.25mL/mm Hg.

Factors Regulating (Affecting) GFR

1. Renal Blood Flow

Renal Blood Flow is the most important factor that is necessary for glomerular filtration.

GFR is directly proportional to renal blood flow. Normal blood flow to both kidneys is 1300 mL per minute. The renal blood flow itself is controlled by autoregulation.

Tubuloglomerular Feedback

• Tubuloglomerular feedback is the mechanism that regulates GFR through renal tubule and macula densa
• Macula densa of the juxtaglomerular apparatus is situated in the terminal portion of the thick ascending limb very close to afferent arteriole.
• Tubuloglomerular Feedback is sensitive to the sodium chloride in the tubular fluid.
• When the glomerular filtrate passes through the terminal portion of the thick ascending segment, the macula densa acts like a sensor.
• Tubuloglomerular Feedback  detects the concentration of sodium chloride in the tubular fluid and accordingly alters the glomerular blood flow and GFR.
• Macula densa cells detect the sodium chloride concentration via Na+-K+-2CI~ co-transporter (NKCC2) in its luminal membrane.

When the concentration of sodium chloride increases in the filtrate

When GFR increases, the concentration of sodium chloride increases in the filtrate.

• By detecting this, the macula densa releases adenosine from ATR Adenosine causes constriction of the afferent arteriole.
• So the blood flow through the glomerulus decreases leading to a decrease in GFR.
• Adenosine acts on afferent arteriole via adenosine A-, receptors. There are several other factors that increase or decrease the sensitivity of tubuloglomerular feedback.

Factors increasing the sensitivity of tubuloglomerular feedback:

1. Adenosine
2. Thromboxane
3. Prostaglandin E2
4. Hydroxyeicosa ethanoic acid

Factors decreasing the sensitivity of tubuloglomerular feedback:

1. Atrial natriuretic peptide
2. Prostaglandin l2
3. Cyclic AMP
4. Nitrous oxide

 

When the concentration of sodium chloride decreases in the filtrate

• Conversely, when GFR decreases, the concentration of sodium chloride decreases in the filtrate.
• Now macula densa secretes prostaglandin (PGE2), bradykinin, and renin.
• PGE2 and bradykinin cause dilatation of afferent arteriole. Renin induces the formation of angiotensin II which causes constriction of efferent arteriole.
• The dilatation of afferent arteriole and constriction of efferent arteriole leads to an increase in glomerular blood flow and GFR.

3. Glomerular Capillary Pressure

The GFR is directly proportional to glomerular capillary pressure. Normal glomerular capillary pressure is 60 mm Hg. When glomerular capillary pressure increases, the GFR also increases. The capillary pressure, in turn, depends upon the renal blood flow and arterial blood pressure.

4. Colloidal Osmotic Pressure

• The GFR is inversely proportional to colloidal osmotic pressure which is exerted by plasma proteins in the glomerular capillary blood. Normal colloidal osmotic pressure is 25 mm Hg.
• During dehydration or increased plasma protein level, the colloidal osmotic pressure is high and GFR decreases.
• During hypoproteinemia, colloidal osmotic pressure is low, and GFR increases.

5. Hydrostatic Pressure in Bowman’s Capsule

• GFR is inversely proportional to this. Normally, it is 15 mm Hg.
• When the hydrostatic pressure increases in the Bowman’s capsule, it decreases GFR.
• The hydrostatic pressure in Bowman’s capsule increases in conditions like obstruction of the urethra and edema of the kidney beneath the renal capsule.

6. Constriction of Afferent Arteriole

The constriction of afferent arteriole reduces the blood flow to the glomerular capillaries which in turn reduces GFR.

7. Constriction of Efferent Arteriole

If the efferent arteriole is constricted, initially the GFR increases because of the stagnation of blood in the capillaries. Later when all the substances are filtered from this blood, further filtration does not occur.

Constriction of Efferent Arteriole is because the efferent arteriolar constriction prevents the outflow of blood from the glomerulus and no fresh blood enters the glomerulus for filtration.

8. Systemic Arterial Pressure

Systemic Arterial Pressure is responsible for the flow of blood through various organs including kidneys.

However, an increase in mean arterial blood pressure up to 180 mm Hg or a reduction up to 60 mm Hg does not alter the renal blood flow or GFR.

Systemic Arterial Pressure is due to the autoregulatory mechanism.

Variation in pressure above 180 mm Hg or below 60 mm Hg affects the renal blood flow and GFR accordingly because the autoregulatory mechanism fails beyond this range.

9. Sympathetic Stimulation

• Afferent and efferent arterioles are supplied by sympathetic nerves.
• The mild or moderate stimulation of sympathetic nerves does not cause any significant change either in renal blood flow or GFR.
• Strong sympathetic stimulation causes severe constriction of the blood vessels by releasing the neurotransmitter substance, noradrenaline.
• The effect is more severe on the efferent arterioles than on the afferent arterioles.
• So, initially, there is an increase in filtration but later it decreases. However, if the stimulation is continued for more than 30 minutes, there is recovery of both renal blood flow and GFR.
• Sympathetic Stimulation is because of a reduction in sympathetic neurotransmitters.

10. Surface Area of Capillary Membrane

GFR is directly proportional to the surface area of the capillary membrane.

If the glomerular capillary membrane is affected as in the cases of some renal diseases, the surface area for filtration decreases. So there is a reduction in GFR.

11. Permeability of Capillary Membrane

• GFR is directly proportional to the permeability of the glomerular capillary membrane.
• In many abnormal conditions like hypoxia, lack of blood supply, presence of toxic agents, etc.
• the permeability of the capillary membrane increases. In such conditions, even plasma proteins are filtered and excreted in urine.

12. Contraction of Glomerular Mesangial Cells

• Glomerular mesangial cells are situated in between the glomerular capillaries.
• Contraction of these cells decreases the surface area of capillaries resulting in a reduction in GFR.

13. Hormonal and Other Factors

Many hormones and other secretory factors alter GFR by affecting the blood flow through the glomerulus.