- 1 What is azotemia?
- 2 What causes azotemia? What is the pathophysiology behind this?
- 3 Who is at risk of developing acute kidney injury?
- 4 What are the signs and symptoms of azotemia?
- 5 How is azotemia treated?
- 6 What are the complications of azotemia?
What is azotemia?
Azotemia refers to a status where there is a rise in the blood urea nitrogen (BUN) and serum creatinine levels. The normal range of Blood urea nitrogen level is between 8 to 20 mg/dL and the normal range for serum creatinine is between 0.7 to 1.4 mg/dL. When the levels of Blood urea nitrogen and serum creatinine are elevated, we call it as azotemia.
The human kidney is responsible for the excretion of these waste products. A normal, healthy human kidney consists of nearly one million functional units which are commonly referred to as the nephrons. The nephrons are the functional units of the kidney because they are primarily invlvled in the production of urine.This process of urine formation ensures that the body gets rid of all the toxic products and other final products of metabolic activities as well as the excess water from the body. This process occurs in such a way that the internal environment is maintained in a normal way, known as homeostasis.
Urine formation is a multi-process. It includes 3 main processes and all of which occurs within the nephrons. These 3 processes are:
- Filtration of blood at the glomerulus.
- Selective reabsorption of important molecules from the filtrate that passes through the renal tubule.
- Secretion of substances into this filtrate by the cells of the tubules.
You may not have heard these big words like filtration at the glomerulus, selective reabsorption and so on. So let’s have a look at the anatomy of the kidneys at the level of nephrons and their functions in detail.
The kidneys are a pair of bean shaped organs that are responsible for filtering the blood and excreting all the waste products and toxins from the body. The kidneys are retroperitoneal organs meaning they lie outside of the peritoneal cavity. Both the kidneys lie on either side of the spine with the right kidney a bit lower than the left due to the presence of the liver on the right side.
The kidneys have several functions and some of the key functions include:
- Excretion of waste products – The kidney filters all the toxins, urea and excess salts from the body.
- Regulation of the blood pressure – The kidneys support in the control of blood pressure by sodium and water regulation. When the blood pressure is low, the kidneys react to this by retaining sodium and water thus increasing the blood pressure. This is brought about by producing angiotensin, which is a hormone that constricts blood vessels signalling the body to retain sodium and water.
- Secretion of Erythropoietin – Erythropoietin is a hormone secreted in response to low oxygen to stimulate the bone marrow to produce more red blood cells.
- Acid balance – The kidneys regulate the chemical balance in the body to let it function properly.
- Fluid balance – When the water intake reduces, the kidneys function in a way to store the water in the body instead of excreting them.
Kidneys are a vital organ for human body and it is vulnerable to numerous problems. Anuria is one way that indicates that something has gone wrong in the renal system.
A nephron is the basic functional unit of the kidney which are involved in the regulation of water and soluble substances within the blood by filtering the blood, reabsorbing whatever the substances that are needed and excreting the rest of the products as urine. Its function is important for the homeostasis of the blood volume, blood pressure and the osmolarity of plasma. The functions of the nephron are regulated by the several hormones in the body such as the parathyroid hormone, antidiuretic hormone and aldosterone.
The nephron consists of two main parts: the glomerulus and the renal tubules.
The glomerulus is a capillary clump which gets blood from an afferent arteriole of the renal circulation. The fluid and solutes of the blood that reaches these arterioles and then the capillary tuft are filtered out of the blood and into the space known as the Bowman’s space, a space created by the Bowman’s capsule. This capsule surrounds the glomerulus and therefore this same Bowman’s capsule is also referred to as the glomerular capsule. This capsule is made up of 2 layers: the visceral and the parietal layers. Both these layers are lined by simple squamous epithelium and therefore do not allow big molecules such as the red blood cells and the large proteins like albumin to pass through these layers. It only allows fluid and small molecules such as glucose and sodium ions to pass through.
The renal tubules are very long structures and at various places along its path, these tubules are given different names. There are 4 parts and they are the proximal convoluted tubule, loop of Henle, distal convoluted tubule and the collecting duct.
- The proximal convoluted tubule
This is the first part of the renal tubule and is the first place where water reabsorption into the blood takes place. This is the site where most of the water and salt is reabsorbed back into blood. Water reabsorption in this part of the renal tubule can occur by both passive diffusion and active transport. Sodium is also reabsorbed at this place. As the sodium is absorbed, water and glucose also follow sodium along the osmotic gradient via a process known as Co-transport. Nearly two thirds of the water within the nephron and 100% of glucose is reabsorbed via the co-transport mechanism in the proximal convoluted tubule.
- The loop of Henle
This is the “U” shaped part of the renal tubule. It consists of a descending limb and an ascending limb. Thee descending limb allows water to pass through its membranes but not the ions. That is, it is completely permeable to water but completely impermeable to ions. Therefore, as a result a large volume of water is reabsorbed at this part of the renal tubule. On the other hand, the ascending limb is very highly permeable to ions but impermeable to water. Therefore a large number of ions will be reabsorbed by this part of the renal tubules.
- Distal convoluted tubule and the collecting duct
The distal convoluted tubule plus the collecting duct are the final places where reabsorption takes place. This part of the nephron is different to the other parts. Here, the permeability to water varies according to the level of certain hormones.
Normally, this part of the nephron is permeable to ions but not to water. Depending on the body needs and the osmolarity of the fluid, antidiuretic hormone will be released. This hormone will act on the distal convoluted tubule and increase its permeability to water hence increasing the water reabsorption. At the same time, the blood volume and the blood pressure will also be increased because of the increased water reabsorption.
The collecting duct also functions in a similar way to the distal convoluted tubule and generally responds to stimuli from hormones just like the distal convoluted tubule.
Once the fluid passes through the collecting duct, they enter the ureters and the leaves the kidney as urine.
What causes azotemia? What is the pathophysiology behind this?
Azotemia can result from three pathophysiological states and they are:
- Pre renal azotemia
- Intra renal azotemia
- Post renal azotemia
Pre renal azotemia
As the name suggests, pre renal azotemia results from a problem that arises before it reaches the kidneys. There is an elevation of the BUN and the serum creatinine levels which results from a problem within the systemic circulation that leads to a reduction of the blood flow to the kidneys. The reduced blood flow stimulates sodium and water retention as the body thinks that there is less blood volume inside. The reduced blood within the circulation is detected by the baroreceptors located within the aortic arch and the carotid sinus and are activated. This leads to the activation of the sympathetic nervous system which results in vasoconstriction of the afferent renal vessels. This leads to secretion of renin. Renin converts angiotensinogen to angiotensin 1 and an enzyme known as angiotensin converting enzyme converts angiotensin 1 to angiotensin 2. Angiotensin 2 is responsible for the release of the aldosterone hormone. This aldosterone acts on the distal collecting ducts and increases the salt and water retention. By increasing the sodium and water retention the blood volume and pressure will be restored.
When the blood volume and pressure is low, hypothalamus is also stimulated to secrete more and more antidiuretic hormone. This hormone acts on the collecting duct to increase reabsorption of salt and water. There is activation of the sympathetic nervous system as well and tis leads to not only enhanced reabsorption of salt and water, but also increases the level of blood urea nitrogen, creatinine, calcium, uric acid and bicarbonate. The exact mechanism of how these levels increase is not yet known. However, the net result will be a reduction in the urine output and reduced urinary excretion of sodium.
A few causes that may lead to pre renal azotemia are:
- Long term diarrhoea
- Heart failure
Intrarenal azotemia is also known as acute renal failure, acute kidney injury or renal-renal azotemia. Here, the blood urea nitrogen and serum creatinine levels rise as a result of an injury to the kidney itself. Acute renal failure is defined as an illness with a sudden and rapid decline in renal function, causing retention of nitrogenous waste products such as blood urea nitrogen and creatinine.
The most common cause of intrinsic azotemia or acute renal failure is acute tubular necrosis.
Causes of intrarenal azotemia include:
- Nephrotoxic drugs
- Infections of the kidney
Post renal azotemia
Post renal azotemia refers to an elevation of the blood urea nitrogen and serum creatinine due to causes within the collecting duct and beyond it, most commonly due to an obstruction anywhere beyond the collecting duct. If there is obstruction in only one kidney, then it rarely causes azotemia. For azotemia to occur, then there should bilateral obstruction of both the kidneys.
Causes of post renal azotemia include:
- A tumour
- Enlarged prostate gland
- Urinary catheter
Who is at risk of developing acute kidney injury?
The following group of people have a higher risk of developing acute kidney injury:
- age >75 years
- pre-existing chronic kidney disease (CKD)
- cardiac failure
- atherosclerotic peripheral vascular disease
- liver disease
- diabetes mellitus
- nephrotoxic medications
What are the signs and symptoms of azotemia?
Azotemia rarely produces any clinical signs and symptoms early during the stage; it always produces features in the late stages.
The signs and symptoms of azotemia include:
- Loss of energy
- Lethargy or sleepiness
- Loss of appetite
- Retention of fuid leading to oedema in the ankles and around the eyes.
- Nausea and vomiting
The signs and symptoms will also vary according to the type of azotemia. For instance, if you have prerenal azotemia, then you will show signs and symptoms that point towards a prerenal azotemia such as excessive bleeding, vomiting, diarrhoea, excessive sweating and polyuria. As you can see all of these symptoms result in a reduction of the blood volume.
Patients with intrarenal azotemia will complain of nocturia,, polyuria, and edema mainly around the eyes whereas patients with a post renal azotemia will complaine of urinary symptoms such as dysuria, frequency, hesitancy & urge incontinence and renal colic.
How is azotemia treated?
Certainly, the treatment of azotemia is going to be different depending on the type of azotemia and also the severity of the condition.
Pre renal azotemia
Pre renal azotemia is easy to treat. The main aim of therapy here is to improve the cardiac output and the renal blood flow. This can be achieved by:
- Fluid therapy – Fluid resuscitation is the key step to improve the urine output and blood pressure. The target is to increase the urine output to at least about 0.5 ml/kg/hour. The normal urine output in a human should be 0.5 ml/kg/hour to 1 ml/kg/hr.
Blood pressure should be monitored accurately and regularly. Fluids should be given carefully to avoid fluid overload and pulmonary oedema.
A daily fluid intake output chart and daily weight measurements are essential to detect any changes in the fluid volume.
- Inotropic agents – Some patients with circulatory shock continue to have a low blood pressure despite adequate fluid therapy. In these situations, inotropic agents such as epinephrine and dopamine can be used. Inotropic agents are drugs that improve the contraction of your heart. They are used to restore the cardiac output and blood pressure to an acceptable level.
Intrinsic renal azotemia
- Haemodialysis – Since the problem lies within the kidneys itself, the kidneys fail to excrete the toxins from your blood adequately therefore these patients will require haemodialysis. Haemodialysis is when a dialysis machine called as an artificial kidney is used to clean the toxins, additional salts and fluids from your blood.
Haemodialysis should be continued till the time the kidney disease seems to be settling with medical therapy.
- Steroids – To reduce the tubular inflammation and oedema.
- Diuretics – If the renal tubules seem to be blocked, then diuretics may be started to flush the tubules.
Post renal azotemia
Post renal azotemia requires an attempt to relieve the obstruction. This is the point where urologists come into play.
- Transurethral catheterization – Catheterization should be considered in all cases with anuria (no urine output at all). If catheterized patients present with anuria, flushing or changing the catheter is required. Catheterization should be done provided that there are no contraindications such as rupture of the urethra. A transurethral catheter is a thin tube that is passed through the urethra in to the bladder to drain the collected urine.
- Suprapubic catheterization – Suprapubic catheterization is considered when transurethral catheterization is not possible or is contraindicated. A suprapubic catheter is directly inserted to the bladder to drain out the urine.
- Percutaneous nephrostomy – When the patient is too unstable to insert a catheter, a percutaneous nephrostomy is preferred. It is a small tube that is inserted through the skin directly into the kidney under ultra sound guidance. If an infection is suspected, prophylactic antibiotics are given before the procedure.
To prevent recurrence of azotemia, the underlying cause should be treated. For example, if it is a ureteric stone, the stone should be removed and if it is a malignancy compressing the ureters, the mass should be removed.
What are the complications of azotemia?
The complications of azotemia include:
- Acute tubular necrosis – Here, the renal tubules begin to die.
- Acute kidney injury
- Miscarriages or abortions – This is because, during pregnancy the mother’s kidney will remove the waste products produced from the baby as well. So, if the mother’s kidneys are not functioning properly, then all the toxins will build up and this can kill the baby. If you are a known patient with a kidney problem and recently found out that you are pregnant, it is important that you inform your doctor regarding this. Your doctor will instruct you to have regular checkups regarding the functional status of the kidneys.