67 Urinary Homeostasis

Regulation of Glomerular Filtration

In a healthy body, GFR remains relatively constant even in the face of substantial changes in arterial blood pressure. By adjusting resistance to the flow of blood, renal autoregulation prevents significant fluctuations in GFR when systemic arterial blood pressure rises or falls. Two mechanisms are involved in this intrinsic control. The myogenic mechanism results from the inherent tendency of vascular smooth muscle to contract when stretched. This means that the diameter of afferent arterioles changes in response to fluctuations in blood pressure. Increasing blood pressure in the afferent arteriole stretches the smooth muscle in the wall of the arteriole. As a result, the smooth muscle will contract and the arteriole will vasoconstrict. This reduces the diameter of afferent arterioles, and blood flow. Decreasing blood pressure in the afferent arteriole removes the stretch of the smooth muscle in the wall of the arteriole. As a result, the smooth muscle will relax and the arteriole will vasodilate. This increases the diameter of afferent arterioles and blood flow. In both cases, the result is a relatively stable GFR.

The second element of renal autoregulation is the tubuloglomerular feedback mechanism The macular densa cells of the distal convoluted tubule are part of the juxtaglomerular apparatus and are responsible for the tubuloglomerular feedback mechanism. The macula densa cells respond to the sodium concentration in the filtrate that flows from the ascending limb of nephron loop into the distal convoluted tubule. The sodium concentration in the filtrate is directly related to the rateglomerular filtration rate (GFR). When GFR is high, there is not enough time for reabsorption, and the filtrate will have a high sodium concentration. The macular densa cells respond to this high sodium concentration by releasing the vasoconstrictor adenosine, which narrows the diameter of the afferent arterioles. Reduced blood flow lowers the net filtration pressure and the GFR, which enhances sodium chloride reabsorption. Conversely, when GFR is low the filtrate will have a low sodium concentration. The release of the paracrine agent by macula densa cells is inhibited. As a result, the afferent arterioles dilate and increase tje blood flow into the glomerulus. The result is to increase net filtration pressure in the glomerulus and increase GFR. This has the opposite effect of macula densa cell activation: it increases the amount of filtered sodium, and it reduces sodium reabsorption.

These two autoregulatory mechanisms help keep the flow of blood through the kidneys relatively constant when mean systemic arterial blood pressure is within a range of approximately 80 mm Hg to 180 mm Hg. However, autoregulation cannot adjust for changes in systemic blood pressure that are outside of this range.

Neural Regulation

The sympathetic nerve fibers that innervate renal blood vessels provide an extrinsic regulatory mechanism for GFR. During extreme stress or blood loss, the sympathetic nervous system must meet the needs of the body as a whole, for example, by temporarily reducing kidney activity and redirecting blood to other vital organs. In such situations, neural controls override renal autoregulation. The sympathetic nerve fibers release the neurotransmitter norepinephrine. Norepinephrine activates alpha-adrenergic receptors on vascular smooth muscle and causes afferent arterioles to constrict. The resulting reduced blood flow into glomerular capillaries lowers net filtration pressure and GFR. This decreased renal blood flow helps maintain blood volume by reducing urine output and increasing perfusion to other body tissues.

Hormonal Regulation

Hormones also regulate GFR. One such mechanism is activated when jutaglomerular (JG) (or granular) cells are stimulated to secrete the enzyme renin. This enzyme begins a process that results in the production of angiotensin II, a powerful systemic vasoconstrictor that also constricts the afferent and efferent arterioles. Angiotensin II also stimulated the contraction of mesangial cells resulting in a decrease in the surface area of the glomerulus. Because renin is released when blood pressure is low, the resulting constriction of the efferent arteriole helps maintain net filtration pressure in the glomerular capillary and consequently, GFR. Another hormone, atrial natriuretic peptide (ANP) increases GFR. ANP is released when the atria of the heart is stretched, for example, in heart failure when blood volume increases due to sodium and water retention. ANP relaxes the mesangial cells of the glomerulus, making more surface area available for filtration. This increases GFR.

Glomerular Filtration Regulation

Hormonal Regulation of Reabsorption and Secretion

Five hormones control the absorption of water, and sodium, chloride, and calcium ions: angiotensin II, aldosterone, antidiuretic hormone, atrial natriuretic peptide, and parathyroid hormone.

Let’s look at each:

Angiotensin II

The renin-angiotensin-aldosterone system is stimulated when blood volume and blood pressure decrease. A decrease in blood pressure reduces the amount of stretch in afferent arteriole walls and stimulates juxtaglomerular cells to release renin into the blood. Renin release is also stimulated directly by sympathetic nerve fiber activity. Renin sets in motion a cascade of events that leads to the production of the hormone angiotensin II.

Angiotensin II plays three primary roles. First, it constricts afferent arterioles, resulting in a reduction in GFR. Second, it stimulates an exchange mechanism. This leads to an increase in the reabsorption of water, sodium ions, and chloride ions. Finally, the hormone prompts the adrenal cortex to secrete the hormone aldosterone.

Aldosterone

The release of aldosterone from the adrenal cortex is stimulated by the presence of angiotensin II as well as an increased concentration of potassium ions. Aldosterone stimulates the insertion of sodium channels in the apical membrane and sodium/potassium pumps in the basolateral membranes of the principal cells of the distal convoluted tubules and the collecting ducts. The result is an increase in the reabsorption of sodium ions. Aldosterone also increases the secretion of potassium ions by principal cells in the collecting duct. Because of the increased reabsorption of sodium ions, more water is reabsorbed and blood volume is effectively increased.

Antidiuretic Hormone (ADH)

Antidiuretic hormone (ADH)acts to decrease urine production by increasing the permeability of principal cells in the late distal convoluted tubule and the collecting duct, thus increasing facultative water reabsorption. Without ADH, the apical membranes of principal cells are relatively water-impermeable. ADH also stimulates the insertion of aquaporins in the apical membrane, allowing water molecules to move more quickly from tubular fluid into the cells and then through the always fairly permeable basolateral membrane and into the blood. When you are dehydrated, ADH is released, and the kidneys conserve water by producing a small volume of very concentrated urine. ADH secretion is controlled bv a negative feedback system. When the water concentration of plasma and interstitial fluid decreases (i.e., when osmolarity increases), more ADH is secreted into the blood, making principal cells more water-permeable. This restores plasma osmolarity towards normal.

Atrial Natriuretic Peptide

Atrial natriuretic peptide is released from the heart in response to large increases in blood volume. This hormone inhibits the reabsorption of water and sodium ions in the proximal convoluted tubule and collecting duct. It also inhibits aldosterone and ADH secretion. The resulting increased sodium ion excretion in urine and the increased urine output lower blood volume and pressure.

Parathyroid Hormone (PTH)

Parathyroid hormone (PTH) affects calcium and phosphate ion reabsorption. It is released by the parathyroid glands in response to a reduced concentration of calcium ions in the blood. PTH stimulates increased reabsorption of calcium ions in the early distal convoluted tubule. PTH also inhibits the reabsorption of phosphate ions in the proximal convoluted tubule, prompting the excretion of phosphate ions in the urine.

Urinary Regulation of Homeostasis

Homeostatic Functions of the Kidneys

The kidneys do most of the work of the urinary system. In addition to being the major excretory organs, the kidneys are important regulators of the volume and chemical composition of blood, and they maintain the correct balance between water and salts, and between acids and bases, in the body. They also regulate blood glucose levels, produce hormones, and metabolize vitamin D to its active form, calcitriol.

Aging and Urinary System Homeostasis

Aging affects all body systems, but perhaps none undergoes as many age-related changes as the urinary system. Among the physical changes in urinary tract function that occur with aging are decreases in bladder capacity and bladder emptying, loss of sphincter muscle tone, and a reduced ability to delay voiding. In addition, age-related conditions such as stroke and Alzheimer’s disease can affect the micturition center in the brain. These are some of the reasons why urinary incontinence is so common in the elderly, affecting up to a third of older men and more than half of older women. Age-related changes in the kidneys include a decrease in organ size, decrease in renal blood flow, and impaired sodium conservation. The number of functional nephrons and the glomerular filtration rate (GFR) also decline with age. In fact, only about two percent of adults over age 70 have normal renal function. In about two thirds of the elderly, the GFR rate is less than 60 milliliters (2 ounces) per minute compared with the normal rate of 120 milliliters (4 ounces) per minute. This has important implications for the many drugs used to treat a variety of age-related conditions. Medication dosages must often be adjusted to compensate for the reduced renal clearance.

Common Dysfunctions of the Urinary System

As noted earlier in the unit, the entire process of urination is known as micturition. A healthy, well functioning urinary system begins with urine being produced by the nephrons in the kidneys, continues via the process of peristalsis bringing the urine into the bladder, and ends with urine exiting through the urethra. However, the urinary system sometimes is compromised when it is permeated by bacteria. Thus far, we have discussed two dysfunctions: renal ptosis, where the fat deposit that holds the kidneys in place fails resulting in one or both kidneys dropping into the pelvis, and urinary tract infections, the most common type of urinary bacterial infections. Later on in the unit, you be introduced to kidney stones, deposits that occur within the urinary tract. Several other urinary disorders are also discussed.

Pyelonephritis

A specific type of kidney infection, pyelonephritis, starts in either the bladder or urethra and ultimately migrate to the kidneys. If the infection does not move to the bladder, it is then referred to as cystitis. Common causes of Pyelonephritis and cystitis are either Escherichia coli or sexual activity and may include flu like symptoms such as fever, vomiting, chills, nausea, and/or frequent, painful, urination. Pyelonephritis and cystitis are usually treated with antibiotics.

Kidney Stones

Kidney stones or renal caculi are relatively large calcium deposits that occur within the urinary tract. Much like pyelonephritis, symptoms can be flu like and include vomiting, nausea, fever, chills. However, the flu like symptoms are usually in combination with flank pain, or pain located one side of the body at the upper abdomen and lower back. Common causes of kidney stones include obesity, dehydration, and a calcium rich diet. Treatment can range from medicinal to lithotripsy, a surgery that employs shock waves to break up the stones to a size that can be passed through the urinary tract, to uteroscopy, a surgery that inserts a scope through the urethra, urinary bladder, and ureter to beak and remove the stone.

Kidney Failure

Kidney failure, also called renal insufficiency, is a medical condition wherein the kidneys cannot filter enough toxins and urea from the blood to maintain proper homeostasis. Kidney failure can occur as either acute and chronic problems. Many of the symptoms of kidney failure as associated with the build up of toxic elements in the blood including:

• increased urea
• increased phosphates
• increased potassium
• general fluid retention

Those in the beginning stages of renal insufficiency might experience swelling from the body retaining fluids. In addition, initial symptoms might include bloody stools, a metallic taste in the mouth, and easy bruising. Treatment for renal insufficiency varies depending on the stage and can include: dietary changes (diet high in carbohydrates and low in protein, salt, and potassium), antibiotics, diuretics to help remove fluid, and/or renal replacement therapy. Renal replacement therapy involves dialysis treatment to aid in the removal of the toxic elements from the blood.

Urinary Homeostasis Summary

• Regulation of Glomerular Filtration
• Glomerular filtration (GFR) remains relatively constant due to renal autoregulation. Renal autoregulation is comprised of:
  • The myogenic mechanism results from the vascular smooth muscle contracting when stretched.
  • The tubuloglomerular feedback mechanism that results in the macular densa cells responding to the filtrate’s high sodium concentration by releasing paracrine agent, that causes vasodialation diameter of the afferent arterioles and reduces blood flow.
• GFR is regulated by:
  • Sympathetic nerve fibers: During extreme stress or blood loss, the sympathetic system will meet the needs of the whole body. The sympathetic nervous can override renal autoregulation and temporarily reduce kidney activity
  • Hormones: The enzyme renin produces angiotensin II. When blood pressure is low, Angiotensin II helps maintain pressure in the glomerular capillary and consequently, GFR
  • Atrial natriuretic peptide (ANP) increases GFR by relaxing the mesangial cells of the glomerulus, making more surface area available for filtration. This increases GFR.
• Hormonal Regulation of Reabsorption and Secretion.
• Five hormones control the absorption of water, sodium ions, chloride ions, and calcium ions:
  • Angiotensin II: Angiotensin II stimulates the adrenal cortex to secrete aldosterone.
  • Aldosterone: Aldosterone stimulates an increase in secretion of potassium and reabsorption of sodium ions and results in increased water reabsorption, leading to increased blood volume.
  • Antidiuretic hormone (ADH): ADH decrease urine production by increasing the water permeability of principal cells in the late distal convoluted tubule and the collecting duct. This, increases facultative water reabsorption.
  • Atrial natriuretic peptide: This is released from the heart in response to large increases in blood volume. The action of ANP inhibit reabsorption of water and sodium ions in the proximal convoluted tubule and collecting duct.
  • Parathyroid hormone (PTH): This is released by the parathyroid glands in response to a reduced concentration of calcium ions in the blood. It results in decrease in phosphate reabsorption in the proximal convoluted tubule and an increase in calcium reabsorption in the distal convoluted tubule.
• Aging and Urinary System Homeostasis
  
• When taking all body systems into account, none undergoes as many age-related changes as the urinary system:
  • decreased bladder capacity and bladder emptying,
  • loss of sphincter muscle tone,
  • reduced ability to delay voiding.
• Age-related conditions such as stroke and Alzheimer’s disease can affect the micturition center in the brain.