Urine Composition and Function

CONCEPT MAP: THE GENERATION OF BIOCHEMICAL ENERGY

29.8 Urine Composition and Function

Urine contains the products of glomerular filtration, minus the substances reabsorbed in the tubules, plus the substances secreted in the tubules. The actual concentrations of these substances in urine at any time are determined by the amount of water being excreted, which can vary significantly with water intake, exercise, temperature, and state of health.

(For identical quantities of solutes, concentration decreases when the quantity of solvent water increases, and concentration increases when the quantity of water decreases.)

About 50 g of solids in solution are excreted every day—about 20 g of electrolytes and 30 g of nitrogen-containing wastes (urea and ammonia from amino acid catabolism, creatinine from breakdown of creatine phosphate in muscles, and uric acid from purine catabolism). Normal urine composition is usually reported as the quantity of each solute excreted per day, and laboratory urinalysis often requires collection of all urine excreted during a 24-hour period.

The following paragraphs briefly describe a few of the mechanisms that control the composition of urine.

Acid–Base Balance

Respiration, buffers, and excretion of hydrogen ions in urine combine to maintain acid–base balance. Metabolism normally produces an excess of hydrogen ions; a portion of these must be excreted each day to prevent acidosis. Very little free hydrogen ion exists in blood plasma, and therefore very little enters the glomerular filtrate.

Instead, the H+ to be eliminated is produced by the reaction of CO2 with water in the cells lining the tubules of the nephrons:

CO2 H2O Carbonic anhydrase H+ + HCO3− To filtrate

To bloodstream Table 29.5 Reabsorption and Secretion in Kidney Tubules

Reabsorbed Ions

Na+, Cl-, K+, Ca2+, Mg2+, PO4 3-, SO4 2-, HCO3- Metabolites

Glucose Amino acids Proteins Vitamins Secreted Ions

K+, H+, Ca2+

Wastes Creatinine Urea Ammonia

Various organic acids and bases (including uric acid) Miscellaneous

Neurotransmitters Histamine

Drugs (penicillin, atropine, morphine, numerous others)

S E C T I O N 2 9 . 8 Urine Composition and Function 889

Automated Clinical Laboratory Analysis

What happens when a physician orders chemical tests of blood, urine, or spinal fluid? The sample goes to a clinical chemistry laboratory, often in a hospital, where most tests are done by automated clinical chemistry analyzers. There are basically two types of chemical analysis, one for the quantity of a chemical (a natural biochemical, a drug, or a toxic substance) and the other for the quantity of an enzyme with a specific metabolic activity.

The quantity of a given chemical in the blood is determined either directly or indirectly. Many chemical components are measured directly by mixing a reagent with the sample—

the analyte—and noting the quantity of a colored product formed by using a photometer, an instrument that measures the absorption of light of a wavelength specific to the product.

For each test specified, a portion of the sample is mixed with the appropriate reagent and the photometer is adjusted to the exact wavelength necessary.

When it is not possible to utilize this direct technique, other indirect methods that produce a detectable product have been devised. Many analytes are substrates for enzyme catalyzed reactions, and analysis of the substrate concentration is therefore often made possible by treating the analyte with appropriate enzymes. Glucose is determined in this manner by utilizing a pair of enzyme-catalyzed reactions: the glucose is converted to glucose 6-phosphate using its hexokinase-catalyzed reaction with ATP; the glucose 6-phosphate is then oxidized by NADP+; and the quantity of NADPH produced is measured photometrically.

The second type of analysis, determination of the quantity of a specific enzyme or the ratio of two or more enzymes, is invaluable in detecting organ damage that allows enzymes to leak into body fluids. For example, elevation of both ALT (alanine aminotransferase) and AST (aspartate aminotransferase) with an AST/ALT ratio greater than 1.0 is characteristic of liver disease. If, however, the AST is greatly elevated and the AST/ALT ratio is higher than 1.5, a myocardial infarction (heart attack) may likely have occurred. When the substance being analyzed is an enzyme, its presence is detected, monitored, and quantified with an assay that employs a substrate of the enzyme in question; levels of the enzyme are measured by monitoring the substrate’s appearance or disappearance. ALT, for example, is determined by photometrically monitoring the disappearance

of NADH in the following pair of coupled reactions (where LD = lactate dehydrogenase):

L@Alanine + a@Ketoglutarate hALT Pyruvate + L-Glutamate Pyruvate + NADH>H+ hLD Lactate + NAD+ As ALT causes pyruvate to form, LD causes the pyruvate to react with NADH to form lactate and NAD+. By knowing how fast this reaction will occur with a given amount of LD, and by knowing how fast a given amount of ALT carries out the first reaction, the amount of ALT can be directly quantified in the sample being examined.

Automated analyzers rely on premixed reagents and automatic division of a fluid sample into small portions for each test.

A low-volume analyzer that provides rapid results for a few tests accepts a bar-coded serum or plasma sample cartridge followed by bar-coded reagent cartridges. The instrument software reads the bar codes and directs an automatic pipette (which removes small samples of precisely measured volumes) to transfer the appropriate volume of sample to each test cartridge. The instrument then moves the test cartridge along as the sample and reagents are mixed, the reaction takes place for a measured amount of time, and the photometer reading is taken and converted to the test result.

A high-volume analyzer with more complex software ran- domly accesses 40 or more tests and runs over 400 tests per hour at a cost of less than 10 cents per test. The end result is a printed report on each sample listing the types of tests, the sample values, and a normal range for each test.

See Chemistry in Action Problems 29.67 through 29.69 at the end of the chapter.

CHEMISTRY IN ACTION

The HCO3- ions return to the bloodstream, and the H+ ions enter the filtrate.

Thus, the more hydrogen ions there are to be excreted, the more bicarbonate ions are returned to the bloodstream.

The urine must carry away the necessary quantity of H+ without becoming exces- sively acidic. To accomplish this, the H+ is tied up by reaction with HPO42- absorbed

at the glomerulus, or by reaction with NH3 produced in the tubule cells by deamina- tion of glutamate:

H+ + HPO4 2- h H2PO4 -

H+ + NH3 h NH4 +

When acidosis occurs, the kidney responds by synthesizing more ammonia, thereby increasing the quantity of H+ eliminated.

A further outcome of H+ production in tubule cells is the net reabsorption of the HCO3 - that entered the filtrate at the glomerulus. The body cannot afford to lose its primary buffering ion, HCO3 -. If HCO3 - were to be lost, the body would have to produce more; the result would be production of additional acid from carbon dioxide by reaction with water. Instead, H+ secreted into the filtrate combines with HCO3- in the filtrate to produce CO2 and water:

H+ HCO3− CO2 + H2O In the filtrate

To bloodstream

Upon returning to the bloodstream, the CO2 is reconverted to HCO3 -. In summary, acid–base reactions in the kidneys have the following results:

• Secreted H+ is eliminated in the urine as NH4 + or H2PO4-.

• Secreted H+ combines with filtered HCO3 -, producing CO2 that returns to the bloodstream and again is converted to HCO3 -.

Fluid and Naⴙ Balance

The amount of water reabsorbed is dependent on the osmolarity of the fluid passing through the kidneys, the antidiuretic hormone–controlled permeability of the collect- ing duct membrane, and the amount of Na+ actively reabsorbed. Increased sodium reabsorption means higher interstitial osmolarity, greater water reabsorption, and decreased urine volume. In the opposite condition of decreased sodium reabsorption, less water is reabsorbed and urine volume increases. “Loop diuretic” drugs such as furosemide (trademarked as Lasix®), which is used in treating hypertension and con- gestive heart failure, act by inhibiting the active transport of Na+ out of the region of the urinary tubule called Henle’s loop. Caffeine acts as a diuretic in a similar way.

The reabsorption of Na+ is normally under the control of the steroid hormone aldosterone. The arrival of chemical messengers signaling a decrease in total blood plasma volume accelerates the secretion of aldosterone. The result is increased Na+ reabsorption in the kidney tubules accompanied by increased water reabsorption.

SUMMARY: REVISITING THE CHAPTER GOALS

1. How are body fluids classified? Body fluids are either intracellular or extracellular. Extracellular fluid includes blood plasma (the fluid part of blood) and interstitial fluid. Blood serum is the fluid remaining after blood has clotted. Solutes in body fluids include blood gases, electrolytes, metabolites, and proteins.

Solutes are carried throughout the body in blood and lymph.

Exchange of solutes between blood and interstitial fluid occurs at the network of blood and lymph capillaries in peripheral tissues.

Exchange of solutes between interstitial fluid and intracellular fluid occurs by passage across cell membranes (see Problems 7, 14–16, 19–20, 24, 27–28, 55–59).

2. What are the roles of blood in maintaining homeosta- sis? The principal functions of blood are (1) transport of solutes and blood gases, (2) regulation, such as regulation of heat and acid–base balance, and (3) defense, which includes the immune

response and blood clotting. In addition to plasma and proteins, blood is composed of red blood cells (erythrocytes), which transport blood gases; white blood cells (leukocytes), for defense functions; and platelets, which participate in blood clotting (Table 29.3) (see Problems 8, 16–18, 26).

3. How do blood components participate in the body’s defense mechanisms? The presence of an antigen (a substance foreign to the body) initiates (1) the inflammatory response, (2) the cell-mediated immune response, and (3) the antibody- mediated immune response. The inflammatory response is initiated by histamine and accompanied by the destruction of invaders by phagocytes. The cell-mediated response is effected by T cells that can, for example, release a toxic protein that kills invaders. The antibody-mediated response is effected by B cells, which generate antibodies (immunoglobulins), proteins that

Understanding Key Concepts 891 complex with antigens and destroy them. Blood clotting occurs

in a cascade of reactions in which a series of zymogens are acti- vated, ultimately resulting in the formation of a clot composed of fibrin and platelets (see Problems 8, 10–13, 23, 25, 29, 30–40).

4. How do red blood cells participate in the transport of blood gases? Oxygen is transported bonded to Fe2+ ions in hemoglobin. The percent saturation of hemoglobin with oxygen (Figure 29.12) is governed by the partial pressure of oxygen in surrounding tissues and allosteric variations in hemoglobin struc- ture. Carbon dioxide is transported in blood as a solute, bonded to hemoglobin, or in solution as bicarbonate ion. In peripheral tissues, carbon dioxide diffuses into red blood cells, where it is converted to bicarbonate ion. Acid–base balance is controlled as hydrogen ions generated by bicarbonate formation are bound by hemoglobin. At the lungs, oxygen enters the cells, and bicarbonate and hydrogen ions leave. A blood pH outside the

normal range of 7.35–7.45 can be caused by respiratory or metabolic imbalance, resulting in the potentially serious conditions of acidosis or alkalosis (see Problems 9, 23, 25–29, 41–52, 60–62).

5. How is the composition of urine controlled? The first essential kidney function is filtration, in which plasma and most of its solute cross capillary membranes and enter the glomerular filtrate. Water and essential solutes are then reabsorbed, whereas additional solutes for elimination are secreted into the filtrate.

Urine is thus composed of the products of filtration, minus the substances reabsorbed, plus the secreted substances. It is composed of water, nitrogen-containing wastes, and electrolytes (including H2PO4- and NH4+) that are excreted to help maintain acid–base balance. The balance between water and Na+ excreted or absorbed is governed by the osmolarity of fluid in the kidney, the hormone aldosterone, and various chemical messengers (see Problems 13, 22, 53–54, 60).

KEY WORDS

Acidosis, p. 886 Alkalosis, p. 886

Antibody (immunoglobulin), p. 880 Antigen, p. 879

Autoimmune disease, p. 882 Blood clot, p. 883

Blood plasma, p. 871 Blood serum, p. 876

Erythrocytes, p. 876 Extracellular fluid, p. 871 Fibrin, p. 882

Filtration (kidney), p. 887 Glomerular filtrate, p. 887 Hemostasis, p. 883

Immune response, p. 880 Inflammation, p. 880

Inflammatory response, p. 879 Interstitial fluid, p. 871 Intracellular fluid, p. 871 Leukocytes, p. 876 Osmolarity, p. 871

Reabsorption (kidney), p. 887 Secretion (kidney), p. 887 Whole blood, p. 876

UNDERSTANDING KEY CONCEPTS

29.7 Body fluids occupy two different compartments, either inside the cells or outside the cells.

(a) What are body fluids found inside the cell called?

(b) What are body fluids found outside the cell called?

(c) What are the two major subclasses of fluids found outside the cells?

(d) What major electrolytes are found inside the cells?

(e) What major electrolytes are found outside the cells?

29.8 In the diagram shown here, fill in the blanks with the names of the principal components of whole blood:

Whole blood

Cells

Fibrinogen

29.9 Fill in the blanks to identify some of the major functions of blood:

(a) Blood carries _________ from lungs to tissues.

(b) Blood carries _________ from the tissues to lungs.

(c) Blood transports _________ from the digestive system to the tissues.

(d) Blood carries _________ from the tissues to the site of excretion.

(e) Blood transports _________ from the endocrine glands to their site of binding.

(f) Blood transports defensive agents such as _________

to destroy foreign material and to prevent blood loss.

29.10 List four symptoms of inflammation.

29.11 Explain how the chemical messenger histamine is biosynthesized and how it elicits each symptom of inflammation.

29.12 Differentiate between cell-mediated immune response and antibody-mediated immune response.

29.13 How does the composition of urine help to maintain a healthy physiological acid–base balance?

ADDITIONAL PROBLEMS

BODY FLUIDS

29.14 What are the three principal body fluids and the approxi- mate percentage of total body water accounted for by each?

29.15 What characteristics are needed for a substance to be soluble in body fluids?

29.16 Give an example of a substance found in tissues that is not soluble in blood. How are components that are not normally soluble in blood transported?

29.17 What effects do the differences in pressure between arterial capillaries, interstitial fluids, and venous capillaries have on solutes crossing cell membranes?

29.18 How does blood pressure compare with the interstitial fluid pressure in arterial capillaries? With the interstitial fluid pressure in venous capillaries?

29.19 What is the purpose of the lymphatic system?

29.20 Where in the body does the lymph enter the bloodstream?

29.21 What is vasopressin?

29.22 What happens when excess secretion of antidiuretic hormone occurs? State two causes of this.

29.23 What is the difference between blood plasma and blood serum?

29.24 At what percent of body-mass loss is collapse very likely to occur?

29.25 What are the three main types of blood cells?

29.26 What is the major function of each of the three types of blood cells?

29.27 What solutes in body fluids are referred to as electrolytes?

29.28 What are the major electrolytes inside cells and outside cells?

29.29 What is an antigen, and what are the three types of responses the body makes upon exposure to an antigen?

29.30 Antihistamines are often prescribed to counteract the effects of allergies. Explain how these drugs work. (Hint:

Electron Configurations and the Periodic Table

The Brứnsted–Lowry Definition of Acids and Bases