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Physiology of Urine Formation, Micturition Reflex and Role of Kidneys in Acid Base Balance

Ultrafiltration or glomerular filtration, Selective reabsorption, Tubular secretion, Micturition and Bladder Emptying, Hydrogen Ion Excretion etc.

Physiology of urine formation

In the process of forming urine, three stages are involved. Among them are:
  • Ultrafiltration or glomerular filtration
  • Selective reabsorption
  • Tubular secretion

Glomerular filtration

In the glomerular capillaries and Bowman's capsule, semipermeable walls allow this process to occur. In addition to carrying useful substances, afferent arterioles in the glomerular capsule can carry harmful substances as well. As the metabolic waste products urea, uric acid, creatinine, and ions are harmful, they are useful substances such as glucose, amino acids, vitamins, hormones, electrolytes, etc. Afferent arterioles have a narrower diameter than efferent arterioles. Hydrostatic pressure is created when the blood leaving the glomerulus differs in diameter from the arteries. Bowman's capsule and semipermeable glomerular capillaries allow this to happen. In addition to carrying useful substances, afferent arterioles in the glomerular capsule can carry harmful substances as well. Despite this, the blood has two opposing pressures, one generated by the plasma proteins, which are typically around 4 kPa (30 mmHg), and the other by the filtrate hydrostatic pressure, which is around 2 kPa (15 mmHg). According to the net filtration pressure,

This means: 55-(30 + 15) = 10mmHg.

Approximately 10 mmHg of net filtration pressure occurs in the glomerular capsule during blood filtration. Small molecules like water and other small molecules like blood cells and plasma proteins can easily pass through the slits of the filtering system, but larger molecules such as blood cells and plasma proteins cannot pass through, and as a result, remain inside capillaries. A filtrate, nephric filtrate of renal glomerular filtrate, is produced in the glomerular capsule, which contains high levels of water, glucose, amino acids, uric acid, urea, and electrolytes. Glomerular filtration rate (GFR) measures how much urine each kidney produces each minute. The two kidneys produce 180 liters of filtrate a day when a healthy adult's GFR is about 125 mL/min

Selective reabsorption

Water, electrolytes, vitamins, hormones, etc., along with other beneficial substances in the filtrate are reabsorbed into the blood in the proximal convoluted tubules of the kidney throughout the kidney cycle. There is passive absorption of some substances, and there is active absorption of others. Most water is reabsorbed through osmosis. The Henle loop receives only 60 to 70% of the filtrate. It is estimated that around 15–20% of the fluid was reabsorbed by the distal convoluted tubule, where more electrolytes, especially sodium, were reabsorbed, so the filtrate entering the collecting ducts is quite dilute. In the body, collecting ducts reabsorb water that is not needed by the body. The active transport of nutrients, including glucose, amino acids, and vitamins, allows them to be reabsorbed into the body. Active transport also reabsorbs positively charged ions, but passive transport mainly reabsorbs negatively charged ions. Reabsorption of water and small proteins by osmosis and pinocytosis respectively. The original filtrate only reaches the distal convoluted tubule in 15-20% of its original volume, where more electrolytes, especially sodium, are reabsorbed and the filtrate enters the collecting ducts as quite diluted.

Tubular secretion

Blood from the peritubular capillaries is diverted into the tubular filtrate in the renal tubules, resulting in tubular secretion. This ensures that waste products such as creatinine and excess H+ and K+ ions are actively excreted in the filtrate. Hyperkalaemia occurs when the kidneys secrete excess K+ ions while reabsorbing Na+ ions. It is essential to maintain normal blood pH that hydrogen ions (H+) are secreted from the kidneys. Penicillin and aspirin may not completely filter out of the blood due to the short period they spend in the glomerulus. By secreting into the filtrate in the convoluted tubules, such substances are removed from the peritubular capillaries. As a result, urine is formed. The urine produced by humans is usually hypertonic.

Micturition reflex

It is called urination or micturition because it involves emptying the bladder of urine stored in that organ. A smooth muscle attached to the bladder wall is called the detrusor. External and internal urethral sphincters form the urethral muscles. The autonomic nervous system controls each of these muscles. It is a voluntary muscle, however, which is controlled by nerves. Adult bladders are typically able to hold 300-400 ml. If the bladder is distended, the brain detects this sensation as 'full bladder'. It is controlled by nerve signals both from the somatic and autonomic nervous system that urine is emptied into the urethra. The autonomic nervous system includes the sympathetic and parasympathetic nervous systems. In addition to the storage phase, the bladder also has an emptying phase.

The guarding reflex and bladder filling
In the filling phase, the external urethral sphincter is voluntarily contracted, while the inner urethral sphincter is sympathetically contracted. Unlike most voluntary muscles, the detrusor is also able to distend without reflex contractions due to the sympathetic nervous system. Guarding reflexes, which prevent involuntary bladder emptying, play a critical role in this process as well. As a result, each spinal reflex is affected by an afferent carried by the pelvic nerves.

Micturition and Bladder Emptying

Under parasympathetic and sympathetic control, the inner and outer urethral sphincters of the bladder relax simultaneously, while the detrusor muscles contract strongly during the micturition phase. As a result, micturition includes:
  • Sphincter striatum relaxation (somatic innervation)
  • Smooth muscle sphincters are relaxed, and the bladder neck is opened (sympathetic innervation)
  • Parasympathetic innervation of the detrusor muscle.
When the urinary bladder wall distends, the wall tension reaches a very slight peak. Approximately 300-400 milliliters into a full bladder, the detrusor, which is intrinsically contractile, makes reflex contractions, which are less powerful than voiding contractions. When filled, afferent firing frequency increases, but until voluntary voiding is determined, cortical control still dominates the micturition reflex. During micturition, additional contractions of the detrusor muscles and relaxation of the external sphincter increase urine flow. The abdominal wall and pelvic floor muscles also aid in the process of emptying the bladder by increasing pressure on it.

Spinal reflex arcs

The bladder urinates through an autonomic reflex in the spinal cord. During voluntary micturition or when the brain has inhibited the action, this reflex relaxes the external sphincter to allow micturition to occur. The brain orders several spinal reflexes according to the extent of filling based on the afferent signals that originate in the bladder as well as from those present in the pelvic floor, the vagina, and the rectum. As a result, micturition is inhibited until the bladder has filled while the external urethral sphincter is activated by the pudendal nerve. Additionally, sympathetic activity stimulates the internal urethral sphincter and inhibits detrusor activity. Impulses from the urethra and neck of the bladder are carried to the spinal cord by the pelvic and hypogastric nerves, and from the hypogastric and pudendal nerves to the spinal cord during bladder filling.

Pontine micturition center

The pontine micturition center (PMC) in the brainstem is activated as the bladder fills with urine. Inhibitory impulses from this center are sent to the spinal reflex arcs, causing the bladder to empty. When there is no regulatory mechanism to control bladder volume, afferents from the bladder and urethra would function as an on-off switch, either causing reflex voiding or storage depending on the volume of urine stored in the bladder. In this way, the voiding reflex is off when the bladder has not distended beyond a critical point, so it is only triggered when a tension receptor in the bladder wall is triggered during the storage phase or filling phase.

Central nervous system regulation

A conscious sensation is experienced when the bladder fills, triggering cortical signals. By inhibiting the purely involuntary response to voiding, the individual can control the urge to void until it is appropriate to do so. Social, sensory, and emotional factors include how safe and tolerable bladder stretching is perceived. In the periaqueductal gray (PAG), a cell group detects bladder distension in addition to relaying bladder afferents to higher brain centers and providing the person with a feeling of sensation. During this process, the anterior cingulate and the prefrontal cortex are also receiving afferents from the pontine center. The result is the suppression of PMC excitation, which inhibits the voiding reflex. After the voluntary signal for voiding is transmitted, PMC neurons become de-inhibited and begin to fire maximally. By stimulating the sacral neurons, the detrusor muscles contract and a sudden increase of intravesical pressure are induced, and the external or voluntary urethral sphincter relaxes. The urethra produces urine when an intravesical pressure is strong enough to overcome the urethral resistance. Thus, both the spinal and cortical reflex arcs control urination. The pontine center is then inhibited until it is determined that urination is appropriate. Moreover, the motor cortex is responsible for controlling the voluntary external urethral sphincter muscle. The prefrontal cortex suppresses tonic inhibition of voiding by suppressing afferents to the PMC from the PAG.

Urethral reflexes

As a result of both urine flow and mechanical distension of the urethra, the detrusor contracts, allowing the bladder to empty fully.

Role of kidneys in acid-base balance

Normal bodily functions depend on the acid-base balance. Arrhythmias and seizures are severe symptoms when this balance is disrupted. Maintaining this balance is therefore extremely important. To alter blood pH, the urinary system relies on two mechanisms. These are the excretion of hydrogen ions as ammonia or dihydrogen phosphate, and the absorption and production of bicarbonate ions.

Hydrogen Ion Excretion

To achieve this, there are two methods:
  • Dihydrogen phosphate (H2PO4 -) is excreted in the form of hydrogen ions - A hydrogen-ATPase pump is responsible for actively transporting hydrogen ions into the lumen of alpha intercalated cells. A large portion of the extraluminal phosphate can be bound to hydrogen ions before excretion as dihydrogen phosphate, which is also reabsorbed by most of the luminal phosphate. Increased hydrogen ion excretion increases blood pH
  • Hydrogen ions are excreted in the form of ammonium (NH4+). - As glutamine is converted to glutamate and ammonium by the proximal convoluted tubule (PCT). To pass the membrane and enter the lumen, ammonium dissociates into ammonia and hydrogen ions. The slurry of hydrogen ions excreted from the lumen by the PCT also acts as a buffer and excretes hydrogen ions excreted downstream by the alpha intercalated cells in the collecting duct, increasing blood pH. The ability to traverse membranes and nephrons is the reason for this. It should be noted that glutamate produced from glutamine can also lead to the formation of bicarbonate (via alpha-ketoglutarate), which may, in turn, be reabsorbed to enhance pH levels.
a. Bicarbonate reabsorption
The kidneys are also capable of reabsorbing bicarbonate ions, which aid in buffering. The PCT facilitates this process. Sodium-Hydrogen exchangers release hydrogen ions into the lumen for combining with any filtered bicarbonate. A carbonic anhydrase then catalyzes the formation of carbonic acid (H2CO3). Carbonic acid, in turn, breaks down into carbon dioxide and water. The water and carbon dioxide are absorbed by the cells. Carbon dioxide and water react with carbonic acid, which breaks down into hydrogen ions and bicarbonate. Then, carbonic anhydrase within the cell reverses this reaction. In turn, the hydrogen ions are transported back into the lumen as bicarbonate is transported into the bloodstream.

b. Bicarbonate production
Bicarbonate can also be produced by the kidney. When cells metabolically produce CO2, they produce bicarbonate ions, which enter the plasma, and hydrogen ions, which are transported into the lumen. Once inside the cell, the bicarbonate ions are transported to the lumen. The hydrogen ions are also needed for the reabsorption of bicarbonate, so this is a useful process. Also, amino acids can produce bicarbonate, resulting in NH4-ions that are then excreted in the urine.
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Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of Pharmaceutical Guidelines, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
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