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Kidney Function and Urinalysis

Learning Objectives

 Understand the importance and role that the kidneys and other organs that compose the urinary system play in homeostasis and the elimination of waste products in your body.

 Understand that excretion is any process that filters waste (carbon dioxide, salts, ammonia, urea, uric acid, etc.) from the blood.

 Know the four major functions that kidneys perform that support homeostasis.

 Know the normal constituents of urine (and the processes by which they become part of urine)

 Be able to identify and understand the significance of abnormal urine components.

 Be able to define specific gravity and understand the meaning of too high or too low specific gravity in urine.

 Urine composition is an important diagnostic tool because it reveals a great deal about body function.

 Urinalysis includes both a macroscopic and microscopic examination of urine.

 Know the principles of urinalysis and be able to apply this knowledge to the diagnosis of various medical disorders.

 A diuretic is any food, drug, or other substance that increases urine production. Caffeine, alcohol, parsley, celery seed and many other foods are natural diuretics.

Urinary System

The kidneys, urinary bladder, ureters and urethra are the parts of your body that make up the urinary system. Without the kidneys and other organ systems in your body that are also involved in the elimination of waste products, toxic substances would build up that would eventually cause your demise. These metabolic wastes include carbon dioxide, heat, salts, ammonia, urea, and uric acid to name a few. The kidneys help maintain homeostasis by eliminating metabolic waste in the form of urine, called excretion. Excretion should not be confused with the term defecation which only refers to the elimination of solid fecal material thorough the intestines as a function of the digestive system. The metabolic waste products eliminated through the kidneys were once chemicals called metabolites in your body. Excretion is the term given to any process that filters waste products from the blood. Diuretics are any foods or drugs that increase urine production. They help reduce edema (swelling) in your body and are often prescribed for those who have high blood pressure, congestive heart failure, glaucoma, and certain types of kidney and liver problems.

Urinalysis can reveal the presence of urinary tract infections, kidney stones, and diseases such as diabetes mellitus or various forms of glomerulonephritis.

Urine Formation

The process of urine formation can be divided into three stages:

 Glomerular Filtration

 ·Tubular Reabsorption and

 Tubular Secretion

Glomerular filtration begins when whole blood is transported into the glomerulus by the afferent arteriole. The elevated blood pressure inside the glomerulus causes water, salts, wastes, nutrients and other small molecules (called the glomerular filtrate) to pass inside the glomerular capsule. Large molecules and formed elements are unable to pass through the capillary wall and are filtered out as a result.

Filterable blood components include water, nitrogenous wastes, nutrients and salts (ions).

Non-filterable blood components include blood cells and platelets (formed elements) and plasma proteins.

The nephrons in the kidney filter about 47.5 gallons of water a day in addition to glucose, sodium, urea and other small molecules. The concentration of the molecules that are dissolved in the glomerular filtrate is about the same as that found in the plasma of the blood. Your textbook has more information on this.

Tubular reabsorption occurs when needed molecules and ions (such as nutrients and salt) are both passively and actively reabsorbed from the convoluted tubules in the nephron into the blood contained in the peritubular capillary network. Water moves passively from the tubule into the blood (passive transport). Carrier proteins are involved in the reabsorption of selected molecules (active transport). However, there is a maximum rate of transport for all molecules and if these substances are present in excessive amounts in the filtrate, they will “spill over” and be present in the urine. This is the case in diabetes mellitus in which the liver and muscles are unable to store glucose as glycogen so the levels of glucose in the blood are elevated above normal and the excess glucose spills over into the urine. Glucose is never found in the urine of healthy individuals.

The filtrate entering the proximal convoluted tubule is divided into types:

 Reabsorbed Filtrate Components – water, nutrients, and salt and

 Non reabsorbed Filtrate Components – water (a much smaller amount), the majority of the nitrogenous waste and excess salts (ions). These components continue to be passed through the nephron and then finally processed into urine.

This process is greatly enhanced by the microvilli in the epithelial cells that line the proximal convoluted tubule because they greatly increase the surface area available for reabsorption. Those substances that cannot be reabsorbed form the tubular fluid enter the loop of the nephron (loop of Henle).

Tubular Secretion is a second way that additional waste substances and excess ions are removed from the blood and become part of the tubular fluid. Certain molecules

such as hydrogen, potassium and ammonium ions, creatinine, and some drugs like penicillin are transported by carrier proteins (active transport) from the blood into the kidney tubule. There are some drugs that should not be given to any one (people or animals) with kidney disease, because the kidneys just can’t process these drugs and remove them from the body. If the drug is necessary, then the dosage will often need to be adjusted in those with malfunctioning kidneys.

Ultimately, at the end of glomerular filtration, tubular reabsorption, and tubular secretion, blood leaving the kidneys has been purified and contains most of the water, nutrients and essential ions that it contained when it first entered the kidneys while the resulting urine contains the wastes and excess substances that have been filtered by the glomerulus and not been reabsorbed as well as substances that have been processed through tubular secretion. Tubular secretion occurs along the entire length of the kidney tubule.

There are four functions that your kidneys perform that support homeostasis. They are:

1. Excretion of Metabolic Wastes (primarily waste products composed of nitrogen such as urea, creatinine (creatine phosphate) and uric acid). A high level of creatinine in urine is an indication of muscle damage. Uric acid can form crystals and precipitate out of blood and collect in the joints causing gout.

2. Maintenance of Water-Salt Balance The kidneys maintain the proper water and salt balance in the blood and in turn, this regulates blood pressure. What this does essentially is to regulate the body’s blood pressure.

3. Maintenance of Acid Base Balance. The kidneys are responsible for controlling the pH of the blood. A pH of 7.4 is considered the normal pH value for human blood. [ A pH value below 7 is acidic and any pH above 7 is alkaline. The pH of normal urine usually ranges from 5-6, which is slightly acidic. Most bacteria cannot survive in acidic environments, so having urine in this pH range helps prevent urinary tract infections. The pH of the urine is also influenced by a person’s diet.

4. Secretion of Hormones. The kidneys are also involved in assisting the endocrine system. Kidneys release rennin, an enzyme that is involved in the stimulation of the secretion of aldosterone. Aldosterone is a hormone produced by the adrenal glands and functions in regulating the water salt balance of the blood. The adrenal glands are found just above each kidney.

Erythropoietin, which is a hormone involved in the production of red blood cells and wound healing, is also secreted by the kidneys. Chronic kidney disease can result in anemia and fatigue due to a decrease in the production of erythropoietin. Erythropoietin is often given to people with kidney failure who are not on dialysis to help increase the synthesis of red blood cells and help increase levels of oxygen that stem from the reduction in red blood cells.

Vitamin D and Other Nutrients

The kidneys are also responsible for the reabsorption of filtered nutrients and the conversion of vitamin D into its active form. Vitamin D is involved in helping to promote the absorption of calcium from the digestive tract.

Urinalysis

Urinalysis can reveal the presence of urinary tract infections, kidney stones, and diseases such as diabetes mellitus or various forms of glomerulonephritis. Urinalysis is used to:

To check a person’s health

To diagnose a possible problem (disease)

To monitor a disease condition and/or treatment (diabetes, kidney disease, blood pressure, etc.)

A complete urinalysis involves both a macroscopic examination of the urine and a microscopic examination. The macroscopic examination involves all observations that can be done by sight and smell without the use of a microscope. The urine characteristics examined include color, odor, clarity, and the presence of blood, sediments, or precipitates. These characteristics are often indicators of your lifestyle and health condition. Each of these properties (characteristics) may vary and may be due to what you have been eating and drinking or to medical diseases. For example, red urine may be due to blood in the sample, or it may be due to your diet or any medication that you may be taking. Eating beets can result in red colored urine. Eating carrots can give your urine an orange appearance. Beets, blackberries, rhubarb, fava beans, and berries are among some of the foods that often change the normal appearance of the color of your urine. The volume of urine that a person produces each day is also significant. A person who produces only a very small amount of dark urine is an indication that the kidneys may not be functioning properly. A person producing copious amounts of urine may be diabetic.

Urinalysis may also be used for drug testing by companies for the purpose of screening potential hires, testing athletes for performance enhancing drugs and also by physicians to determine drug overdose/toxicity or to check to see if a patient is taking prescribed medication. It is also useful for determining whether a woman is pregnant by detecting the presence/absence of the HCG (human chorionic gonadotropin) hormone.

Macroscopic or Gross Examination of Urine

Appearance of Normal Urine

 Can range in appearance from light yellow (straw color) to dark amber in color primarily due to the concentration of the pigment urochrome. Urochrome is the end product of the breakdown of hemoglobin.

 is usually clear or relatively clear and only slightly cloudy  The consistency and color of your urine are often indicators of your lifestyle and

health condition. Each of these signs can vary depending on what you have been eating and drinking to medical diseases.

 The following changes in the normal appearance of urine can be associated with:

 Dark yellow urine may be an indication of dehydration.

 Pale or colorless urine may be due to diabetes or a granular kidney or may be dilute simply because a person is just consuming large amounts of water.

 Bright yellow urine is often caused by multivitamin supplements.

 Red or pink urine may be a sign of bleeding or menstruation or solely the result of having eaten beets for dinner.

 Milky colored urine may be due to the presence of fat globules or pus and may be a sign of a urogenital infection.

 Brown or greenish-brown urine may be an indication of liver problems including hepatitis.

 Green urine is sometimes seen in people who have been on the sedative propofol or be indicative of a Pseudomonas bacterial infection.

 Brown-black urine may indicate poisoning from phenol or certain metals or hemorrhages from renal injuries or even malaria.

 Excessive cloudiness is often caused by abnormal or excessive substances in the urine, including:

 Bacteria (microorganisms)-not normally found in urine)

 Calcium crystals which can indicate kidney stones

 Excess protein (also known as proteinuria)

 Yeast (Candida) and the presence of other fungi

 Pus (infection)

 Prostate fluid

 Blood cells (RBCs), a possible sign of bleeding

 White blood cells (WBCs), a possible sign of infection

 Uric acid crystals (can be an indication of gout)

The presence of these substances must be confirmed with microscopic examination.

Odor

The odor of a person’s urine can vary greatly due to their diet or the presence of certain disease conditions. An ammonia smell may be due to very concentrated urine or certain foods, or cystitis. A fecal odor could be caused by an intestinal-urinary tract fistula. Diabetes can cause the urine to have a sweet smell and acetonuria (the presence of ketones in the urine due to diabetes or starvation) will cause the urine to have an overripe apple smell.

The Macroscopic analysis also includes a chemical examination of urine often performed with chemically treated reagent strips that can be purchased online or in a drug store. This is a colorimetric analysis and these strips test for the presence of:

 pH – acidity/alkalinity. Normal urine ranges from 4.5 to 8 and can fluctuate depending on the types of food consumed. Vegetarians will tend to have more alkaline urine while those who eat meat. Excessive exercise and dehydration will also lower urine pH. Certain types of diseases and prescription drugs can also affect urine pH. Fever and acidosis will lower pH. Anemia, vomiting and urine retention (ischuria) will raise urinary pH.

 Bilirubin – associated with liver problems

 Glucose – is not normally present in urine and can indicate diabetes

 Ketones – can also indicate diabetes

 Leukocytes – a.k.a. White blood cells, and may indicate an infection

 Nitrites – also indicate the presence of an infection

 Protein- may indicate kidney disease

 Specific gravity – measures urine concentration. This value usually ranges from 1.015 – 1.025. Slightly higher or lower values may also be normal for individuals who have diets with either very low or very high fluid content. Low specific gravity indicates kidney disease (nephritis). High specific gravity can be caused by diabetes or nephritis)

 Urobilinogen –can indicate hepatitis and liver problems

Proteins, such as albumin which is present in your blood and helps your body heal, are not normally found in high concentrations in your urine. Small/trace amounts of protein in urine are normal. Temporary high levels of protein in younger people particularly after exercise or an illness are not unusual either, but persistent high levels of protein is significant and can be an indication of kidney disease. There is a new urinalysis test (micro albumin or albumin – creatinine ratio (ACR) test) that can detect very small (micro) amounts of albumin in urine that is gaining popularity, because it can indicate early signs of kidney damage especially in those individuals who are at risk for developing kidney disease. This allows for early treatment and may help prevent kidney damage. The symptoms of extensive kidney damage are foamy urine, and swelling (edema) in hands, feet, face and the abdomen.

Glucose is another substance that is normally retained by the kidneys, so its presence in your urine (glycosuria) is abnormal and may be an indication of diabetes mellitus. Symptoms of diabetes include fatigue, dry mouth, dry skin, excessive thirst (polydipsia), excessive urine output (polyuria) and increased appetite(polyphagia), and the inability to heal wounds properly. Weight loss in spite of increased food intake is also another symptom of diabetes.

Ketonuria (or ketonaciduria), which is the presence of ketones in the urine can also be clinically significant and can indicate unmanaged diabetes mellitus, but can also be present any time the body does not have a sufficient supply of carbohydrates and breaks down fatty tissue to provide alternative energy. The presence of ketones in the urine is also very common in starvation.

Vitamin C (ascorbic acid) reagent strips may also be used to help discover if any abnormality in the results is caused by disease or possibly by any vitamin supplements used.

Microscopic Examination

If the visual/chemical analyses are normal, a microscopic exam may or may not be performed. To prepare a sample for microscopic examination, the urine sample is placed in a centrifuge and spun at high speed to separate the solid components (sediments) from the fluid.

A drop or two of the sediment is then placed on a microscope slide and then examined under the microscope. Cells, crystals, and other substances that are present in the sample are counted and reported. They are also designated as being present under the low power field (magnification) (LPF) or the high power field (HPF). Other, smaller substances may be reported as "few," "moderate," or "many."

Microscopic analysis may reveal the presence of:

 Bacteria, fungi, or parasites

 Crystals (calcium, uric acid, etc.)

 Epithelial cells (cells that line the ureter, bladder and urethra) and whose source may be due to an infection or malignancy

 Red blood cells (RBCs) or White Blood Cells (WBCs)

 Urinary casts, which are multicolored particles that are produced by the kidney in response to a disease condition.

Casts

The presence of casts in a urine sample is a significant finding. Casts are formed by the precipitation of proteins and the agglutination of cells in the renal tubules. Casts are classified into the following major types:

 Hyaline- most common type. They are seen in increased numbers during dehydration, exercise or diuretic medicines.

 Epithelial- are composed of renal tubular epithelial cells. Their presence indicates renal tubular necrosis, viral diseases and the rejection of kidney transplants

 Granular (course and fine)- Granular casts result either from the degeneration of cellular casts, or direct aggregation of plasma proteins or immunoglobulin light chains. They are found following strenuous exercise, and in chronic renal diseases, acute tubular necrosis etc.

 Fatty- contain lipid droplets within the protein matrix of the cast and are identified by the existence of retractile lipid droplets. They are usually seen in the conditions like tubular degeneration, nephrotic syndrome, and hypothyroidism.

 Waxy (aka. Renal failure casts)- Waxy casts represent the final stage of degeneration of cellular casts. They are usually seen in tubular injury of a more chronic nature than granular or cellular casts and are found in individuals who have severe chronic renal disease and renal amyloidosis.

 Red blood cell - The cellular cast appears to result from a clumping of red blood cells that are incorporated in a protein matrix. Disease conditions associated with these type of casts include: pyelonephritis, glomerulonephritis, acute interstitial nephritis, and lupus nephritis

 White Blood Cell- wbc’s are found in or on the casts. These casts typically indicate acute pyelonephritis, but they may also be present in glomerulonephritis. They may also be associated with acute interstitial nephritis, lupus nephritis, and acute papillary necrosis.

 The presence of casts in the urinary sediment provide important diagnostic information because they are formed in the renal parenchyma. The presence of red blood cells always the presence of renal parenchymal disease especially glomerulonephritis. Cast formation is often found in many diseases involving the nephron.

Cells

Cells are cast off from different parts of the genitourinary tract for many different reasons including normal regenerative functions, degenerative and inflammatory conditions, or as part of tumor formation or an infarction. Microscopic evaluation of cells in urine may assist in diagnosing both neoplastic diseases (carcinoma) or non – neoplastic diseases of the urinary tract.

Crystals

Crystals that are found in urine are not always an indication of disease. They can be caused by a diet that has an increased amount of protein or certain drugs. In some cases, however, the presence of crystals in urine can be an indication of a more serious medical condition, organ dysfunction, or an infection in the urinary tract.

Symptoms that would indicate a more serious condition are:

 fever

 severe abdominal pain

 blood in the urine

 jaundice

 fatigue

The type of crystal or unstructured compound is dependent on the pH and osmolality of the urine. Common crystals can normally be found in acid, neutral or alkaline urine. However, abnormal crystals are usually only present in acid or neutral urine.

Urine pH Type of Crystal Potential Indications

Alkaline Calcium phosphate Kidney stone formation (renal calculi)

Alkaline Triphosphate Kidney stone formation (renal calculi)

Obstructive uropathy (flow of urine is blocked) Urinary tract infection Proteus mirabilis infection

Alkaline Calcium Carbonate Kidney stone formation (renal calculi)

Acid Calcium Oxalate Too much oxalate rich foods

Hyperoxaluria which is characterized by recurrent kidney and bladder stones

and often results in end stage renal disease

Ethylene glycol poisoning Diabetes mellitus

Acid Uric Acid Gout, leukemia, chronic nephritis, high purine

metabolism

Acid Hippuric Normal

Acid to Neutral Leucine Sever liver disease

Acid to Neutral Tyrosine Metabolic disorders like kidney and liver disease,

Urine pH Type of Crystal Potential Indications

intellectual disability, body cannot break down

tyrosine

Acid to Neutral Cystine Cystinuria – symptoms cause nausea. Back and

groin pain

Acid to Neutral Cholesterol Renal tubular disease/renal failure

Kidney stones may form when your urine contains an increased amount of calcium, oxalate and uric acid. Additionally, your urine may also be more concentrated and/or have a deficiency of constituents that would normally prevent crystals from sticking together and thus creating the perfect conditions for kidney stones to form.

Types of kidney stones

Knowing the type of kidney stone helps your physician to decide not only the possible cause of the kidney stones but also ways of reducing your risk of getting more kidney stones.

Types of kidney stones include:

Calcium stones

 Most kidney stones are calcium stones, usually in the form of calcium oxalate. Oxalate is a naturally occurring substance found in food and is also made daily by your liver. Some foods have a high oxalate content. If you are prone to getting these types of stones, you should modify your diet to reduce and/or eliminate high oxalate foods.

Dietary factors, high doses of vitamin D, intestinal bypass surgery and some metabolic disorders may increase the concentration of calcium or oxalate in your urine.

Calcium stones may also occur in the form of calcium phosphate. This type of stone is more common in renal tubular acidosis, and other metabolic disorders. They can may also be associated with certain types of migraine headaches or with taking certain medications, including Topamax.

Struvite stones.

 Struvite stones usually form in response to infection, particularly urinary tract infections. These stones can increase in size very quickly and become very large, often without causing any noticeable symptoms.

Uric acid stones.

 Uric acid stones often form in people who don't drink enough fluids and are dehydrated or who lose too much fluid, eat a high-protein diet, and/or those diagnosed with gout. Your family history may increase your risk of forming uric acid stones.

Cysteine stones.

 These stones form in people with a genetic disorder that causes the kidneys to excrete too much of certain types of amino acids (cystinuria).