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Azotemia (''azot'', "nitrogen" + '' -emia'', "blood condition") is a medical condition characterized by abnormally high levels of
nitrogen Nitrogen is the chemical element with the symbol N and atomic number 7. Nitrogen is a nonmetal and the lightest member of group 15 of the periodic table, often called the pnictogens. It is a common element in the universe, estimated at sevent ...
-containing compounds (such as
urea Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid. Urea serves an important ...
,
creatinine Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an impor ...
, various body waste compounds, and other nitrogen-rich compounds) in the
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in th ...
. It is largely related to insufficient or dysfunctional filtering of
blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in th ...
by the
kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...
s. It can lead to
uremia Uremia is the term for high levels of urea in the blood. Urea is one of the primary components of urine. It can be defined as an excess of amino acid and protein metabolism end products, such as urea and creatinine, in the blood that would be no ...
and
acute kidney injury Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both. Causes of AKI are cla ...
(kidney failure) if not controlled.


Types

Azotemia has three classifications, depending on its causative origin: prerenal azotemia, renal azotemia, and postrenal azotemia. Measurements of urea and creatinine (Cr) in the blood are used to assess renal function. For historical reasons, the lab test measuring urea is known as "blood urea nitrogen" (BUN). The BUN:Cr ratio is a useful measure in determining the type of azotemia and will be discussed in each section below. A normal BUN:Cr is equal to 15.


Prerenal azotemia

Prerenal azotemia is caused by a decrease in blood flow (
hypoperfusion Perfusion is the passage of fluid through the circulatory system or lymphatic system to an organ or a tissue, usually referring to the delivery of blood to a capillary bed in tissue. Perfusion is measured as the rate at which blood is deli ...
) to the kidneys. However, there is no inherent kidney disease. It can occur following
hemorrhage Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, vagi ...
, shock,
volume depletion Hypovolemia, also known as volume depletion or volume contraction, is a state of abnormally low extracellular fluid in the body. This may be due to either a loss of both salt and water or a decrease in blood volume. Hypovolemia refers to the los ...
,
congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, an ...
, adrenal insufficiency, and narrowing of the renal artery among other things. The BUN:Cr in prerenal azotemia is greater than 20. The reason for this lies in the mechanism of filtration of urea and creatinine. Renal Plasma Flow (RPF) is decreased due to hypoperfusion which results in a proportional decrease in GFR. In turn, the decreased flow and pressure to the kidney will be sensed by baroreceptors in the Juxtaglomerular (JG) Cells of the afferent arteriole. If the decrease in blood pressure is systemic (rather than occlusion of the renal artery) baroreceptors in the carotid sinus and aortic arch will be stimulated. This leads to sympathetic nerve activation, resulting in renin secretion through β 1 -receptors. Constriction of the afferent arterioles causes a decrease in the intraglomerular pressure, reducing GFR proportionally. Renin is the main effector of the juxtaglomerular baroreceptors. Renin is secreted from granules in the JG cells, and once in the blood stream, it acts as a protease to convert angiotensinogen to angiotensin I, which is converted by angiotensin converting enzyme, to angiotensin II, which, in turn, stimulates aldosterone release. Increased aldosterone levels results in salt and water absorption in the distal collecting tubule. A decrease in volume or pressure is a nonosmotic stimulus for antidiuretic hormone production in the hypothalamus, which exerts its effect in the medullary collecting duct for water reabsorption. Through unknown mechanisms, activation of the sympathetic nervous system leads to enhanced proximal tubular reabsorption of salt and water, as well as urea (BUN), calcium, uric acid, and bicarbonate. The net result of these 4 mechanisms of salt and water retention is decreased output and decreased urinary excretion of sodium (< 20 mEq/L). The increased reabsorption of Na leads to increased water and urea reabsorption from the
proximal tubule The proximal tubule is the segment of the nephron in kidneys which begins from the renal pole of the Bowman's capsule to the beginning of loop of Henle. It can be further classified into the proximal convoluted tubule (PCT) and the proximal stra ...
s of the kidney back into the blood. In contrast, creatinine is actually secreted in the proximal tubule. This generally leads to a BUN:Cr ratio > 20 and a fractional excretion of Na of < 1% and an elevated urine osmolarity.


Primary renal azotemia

Renal azotemia (acute kidney failure) typically leads to
uremia Uremia is the term for high levels of urea in the blood. Urea is one of the primary components of urine. It can be defined as an excess of amino acid and protein metabolism end products, such as urea and creatinine, in the blood that would be no ...
. It is an intrinsic disease of the kidney, generally the result of kidney
parenchyma Parenchyma () is the bulk of functional substance in an animal organ or structure such as a tumour. In zoology it is the name for the tissue that fills the interior of flatworms. Etymology The term ''parenchyma'' is New Latin from the word � ...
l damage. Causes include
kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as ei ...
,
glomerulonephritis Glomerulonephritis (GN) is a term used to refer to several kidney diseases (usually affecting both kidneys). Many of the diseases are characterised by inflammation either of the glomeruli or of the small blood vessels in the kidneys, hence the ...
,
acute tubular necrosis Acute tubular necrosis (ATN) is a medical condition involving the death of tubular epithelial cells that form the renal tubules of the kidneys. Because necrosis is often not present, the term acute tubular injury (ATI) is preferred by pathologist ...
, or other
kidney disease Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can b ...
. The BUN:Cr in renal azotemia is less than 15. In cases of kidney disease, glomerular filtration rate decreases, so nothing gets filtered as well as it normally would. However, in addition to not being normally filtered, what urea does get filtered is not reabsorbed by the proximal tubule as it normally would be. This results in lower levels of urea in the blood and higher levels of urea in the urine as compared to creatinine. Creatinine filtration decreases, leading to a higher amount of creatinine in the blood. Third spacing of fluids such as
peritonitis Peritonitis is inflammation of the localized or generalized peritoneum, the lining of the inner wall of the abdomen and cover of the abdominal organs. Symptoms may include severe pain, swelling of the abdomen, fever, or weight loss. One part or ...
, osmotic diuresis, or low aldosterone states such as
Addison's disease Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adrenal ...
all elevate urea.


Postrenal azotemia

Blockage of urine flow in an area below the kidneys results in postrenal azotemia. It can be caused by
congenital abnormalities A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can r ...
such as
vesicoureteral reflux Vesicoureteral reflux (VUR), also known as vesicoureteric reflux, is a condition in which urine flows retrograde, or backward, from the bladder into one or both ureters and then to the renal calyx or kidneys. Urine normally travels in one direct ...
, blockage of the
ureter The ureters are tubes made of smooth muscle that propel urine from the kidneys to the urinary bladder. In a human adult, the ureters are usually long and around in diameter. The ureter is lined by urothelial cells, a type of transitional ep ...
s by
kidney stone Kidney stone disease, also known as nephrolithiasis or urolithiasis, is a crystallopathy where a solid piece of material (kidney stone) develops in the urinary tract. Kidney stones typically form in the kidney and leave the body in the urine ...
s,
pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ...
, compression of the ureters by
cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...
, prostatic hyperplasia, or blockage of the
urethra The urethra (from Greek οὐρήθρα – ''ourḗthrā'') is a tube that connects the urinary bladder to the urinary meatus for the removal of urine from the body of both females and males. In human females and other primates, the urethra con ...
by kidney or
bladder stone A bladder stone is a stone found in the urinary bladder. Signs and symptoms Bladder stones are small mineral deposits that can form in the bladder. In most cases bladder stones develop when the urine becomes very concentrated or when one is d ...
s. Like in prerenal azotemia, there is no inherent renal disease. The increased resistance to urine flow can cause back up into the kidneys, leading to
hydronephrosis Hydronephrosis describes hydrostatic dilation of the renal pelvis and calyces as a result of obstruction to urine flow downstream. Alternatively, hydroureter describes the dilation of the ureter, and hydronephroureter describes the dilation of th ...
. The BUN:Cr in postrenal azotemia is initially >15. The increased
nephron The nephron is the minute or microscopic structural and functional unit of the kidney. It is composed of a renal corpuscle and a renal tubule. The renal corpuscle consists of a tuft of capillaries called a glomerulus and a cup-shaped structure c ...
tubular pressure (due to fluid back-up) causes increased reabsorption of urea, elevating it abnormally relative to creatinine. Persistent obstruction damages the tubular epithelium over time, and renal azotemia will result with a decreased BUN:Cr ratio.


Signs and symptoms

* Oliguria or anuria (decreased or absent urine output) * Fatigue *
Asterixis Asterixis, more colloquially referred to as flapping tremor, is a tremor of the hand when the wrist is extended, sometimes said to resemble a bird flapping its wings. This motor disorder is characterized by an inability to maintain a position, wh ...
(flapping tremor) * Decreased alertness * Confusion * Pale skin *
Tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...
(rapid pulse) *
Xerostomia Xerostomia, also known as dry mouth, is dryness in the mouth, which may be associated with a change in the composition of saliva, or reduced salivary flow, or have no identifiable cause. This symptom is very common and is often seen as a side eff ...
(dry mouth) * Thirst *
Edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels tight, the area ma ...
, anasarca (swelling) * Orthostatic blood pressure (fluctuates depending on body position) *
Uremic frost Uremic frost is a colloquial description for crystallized urea deposits that can be found on the skin of those affected by chronic kidney disease (CKD). In states of prolonged kidney failure and subsequent uremia, the high level of urea in the b ...
, a condition that occurs when
urea Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid. Urea serves an important ...
and urea derivatives are secreted through the skin in sweat, which evaporates away to leave solid uric compounds, resembling a
frost Frost is a thin layer of ice on a solid surface, which forms from water vapor in an above- freezing atmosphere coming in contact with a solid surface whose temperature is below freezing, and resulting in a phase change from water vapor (a ga ...
. A
urinalysis Urinalysis, a portmanteau of the words ''urine'' and ''analysis'', is a panel of medical tests that includes physical (macroscopic) examination of the urine, chemical evaluation using urine test strips, and microscopic examination. Macroscopic ...
will typically show a decreased urine sodium level, a high urine
creatinine Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an impor ...
-to-serum creatinine ratio, a high urine
urea Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid. Urea serves an important ...
-to-serum urea ratio, and concentrated urine (determined by osmolality and specific gravity). None of these is particularly useful in diagnosis. In pre-renal and post-renal azotemias, elevation of urea exceeds that of the creatinine (i.e., BUN>12*creatinine). This is because
urea Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid. Urea serves an important ...
is readily reabsorbed by the kidneys while creatinine is not. In
congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, an ...
(a cause of pre-renal azotemia) or any other condition that causes poor perfusion of kidneys, the sluggish flow of glomerular filtrate results in excessive absorption of urea and elevation of its value in blood.
Creatinine Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an impor ...
, however, is not absorbable and therefore does not rise significantly. Stasis of urine in post-renal azotemia has the same effect.


Treatment

Prompt treatment of some causes of azotemia can result in restoration of kidney function; delayed treatment may result in permanent loss of renal function. Treatment may include
hemodialysis Hemodialysis, also spelled haemodialysis, or simply dialysis, is a process of purifying the blood of a person whose kidneys are not working normally. This type of dialysis achieves the extracorporeal removal of waste products such as creatinin ...
or peritoneal dialysis, medications to increase cardiac output and increase blood pressure, and the treatment of the condition that caused the azotemia.


See also

*
Kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as ei ...
*
Nephrology Nephrology (from Greek'' nephros'' "kidney", combined with the suffix ''-logy'', "the study of") is a specialty of adult internal medicine and pediatric medicine that concerns the study of the kidneys, specifically normal kidney function (re ...


References


External links

{{Clinical biochemistry blood tests Abnormal clinical and laboratory findings for blood