Chronic kidney disease: functional nephron activity

2021-05-06 03:37 PM

Part of this response occurs due to increased blood arrivals and increased glomerular lobe levels in each of the remaining nephrons, due to enlargement of blood vessels and glomeruli, as well as functional changes caused by vasodilation.

Loss of functional nephrons requires the remaining nephrons to excrete more than water and solutes.

It is reasonable to assume that a decrease in the number of functional nephrons will decrease the glomerular filtration rate (GFR), which will also cause a decrease in renal excretion of water and dissolved substances. However, patients who have lost up to 75-80% of the nephron can still excrete normal amounts of water and electrolytes without accumulation of fluid or serious solutes in body fluids. However, a further reduction in the number of nephrons leads to fluid retention and body solutes, and death often occurs when the number of nephrons falls below 5-10% normal.

In contrast to electrolytes, a lot of metabolic wastes, such as urea and creatinine, are mostly retained in the body as much as the number of nephrons destroyed. The reason for this is that excretion of substances such as creatinine and urea is largely dependent on glomerular filtration, and these substances are not reabsorbed like electrolytes.

Figure. The effect of a 50% reduction in glomerular filtration rate (GFR) on serum creatinine concentration and creatinine excretion rate when the rate of creatinine production remains constant.

Creatinine, for example, is not all reabsorbed, and its excretion is almost directly proportional to its filtration rate.

Creatinine Filtration = GFR x Plasma creatinine concentration = Creatinine excretion rate

Therefore, if GFR decreases, the rate of creatinine secretion also decreases transiently, causing accumulation of creatinine in body fluids and increasing plasma concentrations until creatinine excretion rate returns to normal - similar. as the rate of creatinine secreted in the body. Thus, under stable conditions, the rate of creatinine excretion equals that of creatinine production, despite a decrease in GFR. However, normal rates of creatinine excretion occur at times of high plasma creatinine concentrations.

Some solutes, such as phosphates, urates, and hydrogen ions, are usually maintained near-normal until the GFR falls below 20-30% of normal. Thereafter, the plasma concentration of these substances increases, but is not commensurate with the decrease in GFR. Continuous maintenance of these solutes concentrations in the plasma as GFR decreases is accomplished by incremental excretion of glomerular leaching solutes, which occurs by reducing the rate of reabsorption tubular secretion, or in some cases, by increased tubular secretion.

Figure. Types of adaptations represent the different types of solutes in chronic renal failure. Curve A shows approximate changes in plasma concentrations of solutes such as creatinine and urea that are poorly filtered and reabsorbed. Curve B shows approximate concentrations of solutes such as phosphates, urates and hydrogen ions. Curve C shows approximate concentrations of solutes such as sodium and chloride.

Board. Total excretion and excretion by the kidneys per Nephron in kidney disease




75% lost Nephrons

Number nephron


Total GFR (ml / min)



Single Nephron GFR (nl / min)



Excreted volume for all nephrons (ml/min)



Excreted volume per nephron (nl / min)



 In the case of sodium and chloride ions, their plasma concentrations remain nearly constant even with a severe decrease in GFR (see curve C in the figure). This maintenance is achieved by drastically reducing the reabsorption of these electrolytes in the renal tubules.

For example, when 75% of functional nephrons are lost, each of the remaining nephrons must excrete four times more sodium and urine output than four times normal.

Part of this response occurs due to increased blood arrivals and increased GFR in each of the remaining nephrons, enlargement of blood vessels and glomeruli, as well as functional changes caused by vasodilation. Even a sharp decrease in total GFR of normal renal excretion can be maintained by reducing the rate of the reabsorption of water and tubular solutes.

Figure. Development of urinary co-density in patients with decreased functional nephrons.

Urinary co-density - The kidneys have an inability to concentrate and dilute urine

An important effect on the nephron remaining in the tubule when the flow rate through the tubule is too fast is the kidney tube's ability to concentrate or dilute urine. The kidney's ability to concentrate urine is impaired mainly due to: (1) too fast a volume of fluid flowing through the tubule through the manifold interferes with water reabsorption and (2) too fast flow through the Henle loop. and the manifold interferes with the upstream concentration multiplication mechanism to concentrate solutes in the interstitial fluid. So, corresponding to the nephrons destroyed, the kidney's maximum urine concentration decreases and the permeability and density of urine (measuring the total concentration of solutes) will come close to the value. of the permeability and density of the filtrate.

The kidney's urine dilution mechanism is also impaired when there is a marked decrease in the number of nephrons, due to the rapid blood fluid passing through the loop of Henle and the high concentration of solutes such as urea leads to a relatively high concentration of tubular solutes. in each part of the nephron. As a result of the above process, the dilution capacity of the kidneys will be impaired and the permeability and a minimum density of urine will be close to that value of the dialysis solution. Since urine concentration is much more impaired than dilution in chronic kidney disease, an important kidney clinical test to assess the kidney's ability to concentrate urine is to limit the amount of water to drink. people within 12 hours or more.

Effects of kidney failure on the amount of fluid in the body - Hyperaemia

The effect of chronic kidney disease on body fluids depends on (1) water intake and food, (2) the degree of impaired renal function. Assuming that a person with renal failure completely eats the usual amount of water and food, the concentration of substances in the extracellular fluid is estimated. The important effects include (1) systemic oedema resulting from water salt retention; (2) acidosis results from impaired renal function in the elimination of acids from the body; (3) high concentrations of non-protein nitrogen compounds — particularly urea, creatinine, and uric acid — resulting from impaired excretion of intermediates and protein metabolites; and (4) high concentrations of other substances excreted by the kidneys, including phenols, sulphates, phosphates, potassium, and base guanidine.

Diagram. Effects of renal failure on extracellular fluid components. NPN-non-protein nitrogen compound.

Fluid retention and oedema formation in chronic kidney disease

If the amount of water is restricted immediately after the onset of acute kidney damage, the total amount of fluid in the body may increase only slightly. If the amount of fluid entering the body is not limited and the patient drinks according to normal needs, the fluid in the body will increase rapidly.

With chronic kidney disease, if the amount of salt and fluid intake is not too much, the accumulated fluid in the body will not be much until kidney function falls below 25% of normal. To account for this, as discussed previously, the remaining nephrons still excrete large amounts of salt and water. Although the body retains only a little fluid, the increased secretion of renin and angiotensin II often occurs in renal ischemia, which can lead to severe hypertension in CKD patients. Hypertension develops in most patients with reduced kidney function, and dialysis is essential to ensuring a patient's life. In many patients, a radical reduction of salt intake along with the removal of extracellular fluid by dialysis can help control hypertension. Patients still have hypertension even after large amounts of sodium have been eliminated through dialysis. In this group,

Urea and non-protein nitrogenous compounds (uraemia)

Non-proteolytic substances include urea, uric acid, creatinine, and a number of other unimportant compounds. These nonprotein nitrogen families, which are the final metabolic products of protein metabolism, must be removed from the body to ensure the continuous protein metabolism of the cells. Nonprotein nitrogen concentrations, particularly urea, can increase 10-fold within 1-2 weeks in patients with complete renal failure. With chronic kidney disease, the concentration of substances increases in proportion to the degree of decline in functional nephrons. For this reason, measuring concentrations of substances, especially urea and creatinine, provides important information for assessing the severity of chronic kidney disease.

Acidosis in chronic kidney disease

Every day, the body produces 50-80mmol more metabolic acids than metabolic alkalis. Therefore, when the kidneys fail to function, acids will accumulate more in body fluids. Buffer systems in body fluids can buffer 500 to 1000 mmol acids so that the H + concentration in the extracellular fluid does not increase to a lethal level, and bone phosphate compounds can buffer up to several thousand mmol H +. However, when the buffers are used up, the blood pH will drop drastically and the patient can fall into a coma or die if the pH drops below 6.8.

Anaemia in chronic renal failure due to decreased Erythropoietin excretion

anaemia often occurs in patients with severe chronic kidney disease. The most important cause of anaemia is decreased renal excretion of erythropoietin, which stimulates the bone marrow to produce red blood cells. If the kidneys are severely damaged, they cannot produce an adequate amount of erythropoietin, which leads to a decrease in the number of red blood cells and ultimately anaemia.

Since 1989 recombinant erythropoietin has been produced to support the treatment of anaemia in patients with chronic renal failure.

Osteoporosis in chronic kidney disease is caused by decreased production of active Vitamin D and the kidney's ability to maintain phosphate

Chronic kidney disease also causes osteoporosis, a condition in which part of the bone is absorbed again and becomes weaker as a result. The most important cause of this condition is: Vitamin D is metabolized by a two-stage process, first in the liver and then in the kidney, it is converted to 1,25dihydroxycholecalciferol before taking. increases the absorption of calcium from the intestine. Therefore, severe kidney damage reduces the concentration of active Vitamin D in the blood, thereby reducing intestinal absorption of calcium and decreasing calcium in the bones.

An important cause of bone demineralization in chronic kidney disease is an increase in serum phosphate concentration due to a decrease in GFR. Increased serum phosphate increases phosphate binding to calcium in plasma, thereby reducing the concentration of calcium ions in the plasma, thereby stimulating parathyroid hormone secretion. This hyperparathyroidism stimulates the release of calcium from the bones, causing further bone demineralization.

Hypertension and kidney disease

Hypertension worsens damage to the kidneys and kidney blood vessels and is a major cause of end-stage chronic kidney disease.

Kidney function abnormalities can lead to increased blood pressure. So, there is an association between kidney disease and hypertension, in some cases forming a pathological spiral: damage to the kidney initially leads to increased pressure in the blood vessels, which in turn raises pressure. This continues until the end-stage chronic kidney disease develops.

Not all kidney diseases lead to hypertension because damage to certain parts of the kidneys leads to the non-hypertensive uremic syndrome. However, some kidney damage has a high risk of high blood pressure. Classification of kidney disease with or without hypertension is discussed in the next sections.

Kidney damage reduces the ability to excrete sodium and water, contributing to increased blood pressure.

Kidney damage reduces the ability to excrete sodium and water, almost always leading to increased blood pressure. Therefore, lesions that reduce GFR or increase tubular reabsorption often lead to increased blood pressure of varying degrees.

Some of the specific kidney abnormalities that can lead to high blood pressure are listed below:

1. Increases renal vascular resistance, reduces blood flow to the kidneys and decreases GFR. An example is renal artery stenosis, which causes hypertension.

2. Reducing the filtration coefficient in the glomerular capillaries, thereby reducing GFR. An example is chronic glomerulonephritis, leading to an inflammatory response and thickening of the glomerular basal membrane, thereby reducing the glomerular filtration coefficient.

3. Excessive reabsorption of sodium in the renal tubules. One example is hypertension caused by excessive excretion of aldosterone, which increases sodium reabsorption, especially in the manifold.

Once an increase in blood pressure has formed, the water and sodium excretion of the kidneys return to normal due to the high pressure in the arteries, increasing diuretic and sodium in the urine, so the amount of sodium and water in and out. the body will return to balance again. Even if the renal capillary resistance increases or decreases the glomerular filtration factor, GFR may return to almost normal levels after episodes of hypertension. Likewise, when tubular reabsorption increases, which occurs during excessive excretion of aldosterone, the rate of urinary excretion decreases initially but then returns to normal after episodes of hypertension. Therefore, after each progressive increase in blood pressure, there may be no signs of decreased sodium and water excretion function compared with prior hypertension.

Hypertension due to uneven kidney damage and increased Renin excretion

If one part of the kidney is ischemic and the rest is not anaemic, occurs when a kidney artery is constricted, and the kidney tissue is anaemic secreting a large amount of renin. This secretion increases the formation of angiotensin II, which in turn can lead to increased blood pressure. The body's next chain of reactions to high blood pressure is that (1) anaemia in the kidney parenchyma will excrete less water and salt than usual; (2) Renin is excreted by anaemic renal tissue, followed by an increase in angiotensin II formation, thereby acting on non-anaemic renal tissue leading to increased salt and water retention; and (3) normally, excessive salt retention leads to an increase in blood pressure.

A similar type of hypertension is caused by anaemia in different parts of the kidney as a result of hardening of the kidney vessels or damage to the vessels in specific locations of the kidney. When this happens, the anaemia nephrons excrete less salt and water but excrete more renin, leading to increased angiotensin II formation. Angiotensin II elevated levels will impair the function of the surrounding parts, namely impair the function of normal nephrons in the excretion of water and sodium. The end result is the formation of hypertension, which in turn restores full kidney function in water and sodium excretion, and a balance of salt and water intake is maintained, but at the time of high blood pressure.

Kidney diseases damage all of the nephron, leading to chronic kidney disease but may not lead to high blood pressure

Losing a large number of nephrons, which occurs when one kidney and part of the other is lost, most often leads to chronic kidney disease if the amount of lost renal parenchyma is large enough. If the remaining nephrons are normal and the salt intake is not too great, this condition may not lead to clinical symptoms of hypertension as a gradual increase in blood pressure will lead to increased GFR and decreased relapse. renal tubular sodium absorption from the remaining nephrons to promote adequate excretion of salt and water in the urine, even with a small number of intact nephrons remaining. However, patients with this type of abnormality can experience paroxysmal hypertension if stress factors are present, for example eating large amounts of salt. In this case, the kidneys cannot clear out all the salt to maintain normal blood pressure with only a small amount of the remaining functional nephrons.

The effectiveness of treatment of hypertension depends on increasing the kidneys' ability to excrete salt and water, or increasing GFR or decreasing renal tubular reabsorption so that a balance between saline intake and excretion can be maintained. at lower blood pressure.

This effect can be achieved with neurotransmitters and salt-water retention hormones (for example, βadrenergic inhibitors, angiotensin receptor resistance, or angiotensin-converting enzyme receptors), or renal vasodilators. and increased GFR (eg, calcium channel blockers ..) or diuretics directly inhibit tubular salt and water reabsorption.

Specific disorders of the renal tubules

If any of the essential genes are lost or abnormal, the tubules may be deficient in one of the transporting proteins or one of the enzymes required for the transport of solutes across the tubular epithelium. In other cases, too many transport enzymes or proteins are produced. As a result, many inherited tubular disorders occur due to abnormal transport of substances or groups of substances across the tubular membrane. In addition, damage to the renal tubular epithelial membrane due to toxins or drugs can cause serious renal tubular disorders.

Glucose Urinary - Impaired renal function during glucose reabsorption

In the case of hyperglycaemia, blood sugar may be normal, but the renal tubular glucose reabsorption may be limited or lost. As a result, although the amount of glucose in the blood is normal, a large amount of glucose still passes through the urine every day. Since diabetes also causes glucose in the urine, but this is a benign condition, it is necessary to eliminate the above causes before diagnosing a patient with diabetes.

Aminoaciduria-Impaired renal function in Amino Acid reabsorption

Some amino acids are reabsorbed through the same transport system, while other amino acids have their own transport system. Rarely, a condition called generalized aminoaciduria results from insufficient reabsorption of all amino acids; more commonly, a lack of specific transport channels can result in (1) urinary cystine, large amounts of cystine are not reabsorbed and often crystallize in the urine to form kidney stones; (2) glycinuria, no reabsorption of glycine; or (3) urinary beta-amino isobutyric acid, occurring in approximately 5% of the population with no clinical manifestations.

Renal hypophosphatemia - Impaired renal function in phosphate reabsorption

In renal hypophosphatemia, the renal tubules are not able to reabsorb enough phosphate ions, while the phosphate concentration in body fluids is very low. This usually does not cause serious abnormalities immediately because the phosphate concentration in the extracellular fluid can vary over a large range without causing intracellular dysfunction. However, over a long period of time, low phosphate levels will reduce calcium in the bones, leading to rickets. This type of rickets does not respond to vitamin D treatment, unlike other types of rickets that often respond quickly to vitamin D treatment.

Renal tubular acidosis - Impaired tubular function in H + ion secretion

In tubular acidosis, the tubules are not able to excrete enough H + ions.

As a result, large amounts of sodium bicarbonate are continuously lost in the urine. This discontinuity causes a continuing metabolic acidosis.

This type of kidney abnormality can result from an inherited abnormality, or it can occur as a result of extensive damage to the kidney tubes.

Diabetes insipid - Impaired renal function in response to Antidiuretic Hormones

When the renal tubules do not respond to antidiuretic hormones, a large amount of dilute urine can be excreted out. If the body is well hydrated, this condition is rarely dangerous to the patient. However, when the water supply is insufficient, the body quickly becomes dehydrated.

Fanconi-Deficiency syndrome in the re-absorption of all substances in the renal tubules

Fanconi syndrome is often associated with increased urinary excretion of all cytoplasm including amino acids, glucose, and phosphates. In severe cases, there may be some other manifestations such as (1) impaired resorption of sodium bicarbonate, resulting in metabolic acidosis; (2) increased excretion of potassium and sometimes calcium; and (3) diabetes insipidus.

There are many causes of Fanconi's syndrome, which results in the inability of all renal tubular cells to transport various substances. Some of the causes include (1) genetic defects in cell transport mechanisms, (2) toxins or drugs that damage renal tubular epithelial cells, and (3) injury to tubular cells due to ischemia. Proximal tubular cells are particularly affected by Fanconi syndrome due to renal tubular damage because these are the cells that play a major role in the reabsorption and secretion of drugs and toxins.

Bartter Syndrome-Reduced Sodium, Chlorine and Potassium reabsorption in the loop of Henle

Bartter's syndrome is a rare disorder on the recessive-chromosome gene that often causes impairment of the 1Natri-2Clo-1 Potassium co-transport system or a lack of potassium channels on the luminal membrane or the chlorine channel on the basolateral membrane in segmented bulge branches up Henle straps. These disorders lead to increased renal excretion of water, sodium, chlorine, potassium and calcium. Renal loss of salt and water leads to a slight decrease in circulating volume, resulting in activation of the renin-angiotensin aldosterone system. The increased aldosterone and increased flow rate through the distal tubule are due to a lack of reabsorption in the loop of Henle, which will stimulate the secretion of potassium and H + in the manifold, ultimately causing hypokalaemia and metabolic alkalosis.

Gitelman syndrome-Reduced NaCl reabsorption in distal tubules

Gitelman syndrome is a recessive disorder of the chromosomal recessive gene usually on the sodium-chloride co-transporter channel, a thiazide-sensitive nerve in the distal tubule. Patients with Gitelman syndrome have a number of characteristics such as those with Bartter's syndrome - loss of salt and water, a slight decrease in circulating volume, and activation of the renin-angiotensin-aldosterone system - although these abnormalities are typically less severe in patients with Gitelman syndrome.

Since tubular defects in Bartter and Gitelman syndromes are irreversible, treatment is primarily focused on replacing the loss of NaCl and Potassium. Some studies suggest that inhibiting prostaglandin synthesis with non-steroidal anti-inflammatory drugs and anti-aldosterone drugs, such as spironolactone, may be effective in modulating hypokalaemia.

Liddle-Increased Sodium Reuptake Syndrome

Liddle's syndrome is a rare disorder of the chromosomal dominant gene often caused by different mutations in the sodium channel epithelium (ENaC), where amiloride is sensitive in the distal tubule and the manifold. These mutations induce overactive ENaC, leading to increased sodium and water reabsorption increased blood pressure and metabolic alkalosis, similar to changes that occur with excessive secretion of aldosterone (the early stages of the control). increased aldosterone).

However, in patients with Liddle's syndrome, sodium retention reduces renin secretion and the angiotensin II system, thereby reducing aldosterone secretion in the adrenal glands. Luckily, Liddle's syndrome can be treated with amiloride diuretics, which inhibit the overactive ENaC.



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