WATER-MINERAL METABOLISM

Reabsorbtion. Lenght of renal tubules is about 100 km. So, all important for our organism are reabsorbed during passing these tubules. Epitelium of renal tubules reabsorb per day 179 L of water, 1 kg of NaCl, 500 g of NaHCO3, 250 g of glucose, 100 g of free amino acids.

All substances can be divided into 3 group:1. Actively reabsorbed substances.2. Substances, which are reabsorbed in a little amount.3. Non-reabsorbed substances. To the first group belong Na+, Cl-, Mg2+, Ca2+, H2O, glucose and other

monosaccharides, amino acids, inorganic phosphates, hydrocarbonates, low-weight proteins, etc.

Na+ reabsorbed by active transport to the epitelium cell, then – into the extracellular matrix. Cl- and HCO3

- following Na+ according to the electroneutrality principle, water – according to the osmotic gradient. From extracellular matrix substances go to the blood vessels. Mg2+ and Ca2+ are reabsorbed with help of special transport ATPases. Glucose and amino acids use the energy of Na+ gradient and special carriers. Proteins are reabsorbed by endocytosis.

Urea and uric acid are little reabsorbable substances.Creatinin, mannitol, inulin and some other substances are non-reabsorbable.Some substances (K+, ammonia and other) are secreted into urine in the distal part of

tubules. K+ is changed to Na+ by the activity of Na+-K+ATPase.

Peculiarities of biochemical processes in kidney.

Kidney have a very high level of metabolic processes. They use about 10 % of all O2, which used in organism. During 24 hours through kidney pass 700-900 L of blood. The main fuel for kidney are carbohydrates. Glycolysis, ketolysis, aerobic oxidation and phophorillation are very intensive in kidney. A lot of ATP formed in result.

Kidney have plenty of different enzymes: LDH (1, 2, 3, 5), AsAT, AlAT. Specific for kidney is alanine amino peptidase, 3rd isoform.

Organic compounds of urine.Proteins. Healthy people excretes 30 mg of proteins per day. As a rule

these are low weight proteins.Urea. This is main part of organic compounds in urine. Urea nitrogen is

about 80-90 % of all urine nitrogen. 20-35 g of urea is excreted per day in normal conditions.

Uric acid. Approximately 0,6-1,0 g of uric acid is excreted per day in form of different salts (urates), mainly in form of sodium salt. Its amount depends from food.

Creatinin and creatin. Near 1-2 g of creatinin is excreted per day, what depended from weight of muscles. This is the constant for each person. Men excrete 18-32 mg of creatinin per 1 kg of body weight per day, women – 10-25 mg. Creatinin is non-reabsorbable substance, so this test used for evaluating of renal filtration.

Amino acids. Per day healthy person excretes 2-3 g of amino acids (free amino acids and different low weight molecule peptides). Also products of amino acids metabolism can be found in the urine.

Couple substances. Hypuric acid (benzoyl glycine) is excreted in amount 0,6-1,5 g per day. This index increases after eating a lot of berries and fruits, and in case of protein’s decay in the intestines.

Indican (potassium salt of indoxylsulfuric acid). Per day excrition of indican is about 10-25 g. Increasing of indican’s level in urine is due to inrtensification of decay proteins in the intestines and chronic diseases, which are accompanied by intensive decopmosition of proteins (tuberculosis, for example).

Organic acids. Formic, acetic, butyric, β-oxybutyric, acetoacetic and some other organic acids are present in urine in a little amount.

Vitamines. Almost all vitamines can be excreted via kidney, especially, water-soluble. Approximately 20-30 mg of vit C, 0.1-0.3 mg of vit B1, 0.5-0.8 mg of vit B2 and some products of vitamine’s metabolism. These data can be used for evaluating of supplying our organism by vitamines.

Hormones. Hormones and their derivates are always present in urine. Their amount depends from functional state of endocrinal glands and liver. There is a very wide used test – determination of 17-ketosteroids in urine. For healthy man this index is 15-25 g per day.

Urobilin. Present in a little amount, gives to urine yellow colour.Bilirubin. In normal conditions present in so little amount that cannot be found by routine methods of

investigations.Glucose. In normal conditions present in so little amount that cannot be found by routine methods of

investigations.Galactose. Present in the newborn’s urine, when digestion of milk or transformation of glalactose into

glucose in the liver are violated.Fructose. It is present in urine very seldom, after eating a lot of fruits, berries and honey. In all other

cases it indicates about liver’s disorders, diabetes mellitus.Pentoses. Pentoses are excreted after eating a lot of fruits, fruit juices, in case of diabetes mellitus and

steroid diabetes, some intoxications.Ketone bodies. In normal conditions urine contains 20-50 mg of ketone bodies and this amount cannot

be found by routine methods of clinical investigations.Porphyrines. Urine of healthy people contains a few I type porphyrines (up to 300 mkg per day).

Regulation of urine formation.Na-uretic hormone (produced in heart) decrease

reabsorbtion of Na+, and quantity of urine increased.

Aldosteron and some other hormones (vasopressin, renin, angiotensin II) increase Na-reabsorbtion and decrease quantity of urine.

Role of kidney in acid-base balance regulation.Kidney have some mechanisms for maintaining

acid-base balance. Na+ reabsorbtion and H+ secretion play very important role.

1. Primary urine has a lot of Na2HPO4 (in dissociated form). When Na+ reabsorbed, H+ secreted into urine and NaH2PO4 formed.

2. Formation of hydrocarbonates. Inside renal cells carboanhydrase forms from CO2 and H2O H2CO3, which dissociated to H+ and HCO3

-. H+ excreted from cell into urine (antiport with Na+) and leaded with urine. Na+ connect with HCO3

-, NaHCO3 formed and go to the blood, thereupon acidity decreased.

3. Formation of free ammonia. NH3 used for formation of NH4

+ (H+ ion associted), and different acid metabolites excreted as ammonia salts.

Role of kidney in water balance regulation.Excessive entrance of water leads to dilution of

extracellular fluid. Decreasing of osmolality inhibits secretion of antidiuretic hormone. Walls of collective tubules stay non-penetrated to water and dilutive urine formed.

If volume of blood circulation increases, circulation in kidney increases also and hyperosmotic medium of kidney medulla removed. Some substances in these conditions return into blood. So, excess of water carried with urine and a lot of soluble substances are reabsorbed into blood. After water loading stopped, hyperosmolality in kidney medulla returns for previous stage during some days.

Melting point of water – 0 oC; boiling point – 100 oC.

Water plays an important role in the thermal regulation of living organisms. Water's high heat capacity coupled with the high water content found in most organisms (between 50% and 95%, depending on species) contributes to the maintenance of an organism's internal temperature.

Water is a remarkable solvent. Water's ability to dissolve a large variety of ionic and polar substances is determined by its dipolar structure and its capacity to form hydrogen bonds. Salts such as sodium chloride (NaCI) are held together by ionic (or electrostatic) forces. They dissolve easily in water because dipolar water molecules are attracted to the Na+ and Cl- ions.

Organic molecules with ionizable groups and many neutral organic molecules with polar functional groups also dissolve in water. Their solubility is due primarily to the hydrogen bonding capacity of water. Nonpolar compounds are not soluble in water. Because they lack polar functional groups, such molecules cannot form hydrogen bonds.

The state and distribution of water in the organism. There are two water compartments in the body:- Intracellular water- Extracellular water Extracellular fluid is divided into:- interstitial fluid- Plasma Biological role of water: Water is an essential constituent of cell structures and

provides the media in which the chemical reactions of the body takes place and substance are transported.

It has a high specific heat for which, it can absorb or gives off heat without any appreciable change in temperature.

It has a very high latent heat. Thus, it provides a mechanism for the regulation of heat loss by sensible or insensible perspiration on the skin surface.

The fluidity of blood is because of water.

Distribution of water in an adult man, weighing 70 kg

CompartmentBody weight

(%)Volume (l)

Total 60 42

ICF 40 28

ECF 20 14

Interstitial fluid 15 10,5

Plasma 5 3,5

Water balance. Endogenous water. Water intake.Water is supplied to the body by exogenous and endogenous

sources.Exogenous water: water intake is highly variable which may

range from 0,5-5 liters. Ingestion of water is mainly controlled by a thirst centre located in the hypothalamus.

Endogenous water: the metabolic water produced within the body is the endogenous water. This water (300-350 ml/day) is derived from the oxidation of foodstuffs. It is estimated that 1g each of carbohydrate, protein and fat, respectively, yield 0,6 ml, 0,4 ml and 1,1 ml of water.

Water output.Water losses from the body are variable. There are four

distinct routes for the elimination of water from the body: urine, skin, lungs and feces.

Regulation of Water Metabolism

1. Antidiuretic hormone or Vasopressin which has got the property to enhance water reabsorption

2. Hypothalamus known as a thirst centre. Besides this, osmoconcentration of plasma also stimulates supraoptic and paraventricular nuclei

3. Adrenal Cortex. Aldosterone has controll excretion of sodium and potassium by the kidneys

4. Rennin-Angiotensin system. Angiotensin II stimulates the synthesis and secretion of aldosterone and the release of vasopressin, and thereby increases renal absorption of Na+ and H2O.

5. Prostaglandins. They may also increase urinary loss of water by inhibiting the antidiuretic effect of vasopressin and by increasing the urinary sodium.

6. Solutes. Osmotic effect of Na+ helps to retain water in extracellular fluids. Elevation in plasma Na+ raises the ECF volume in primary aldosteronism while an increase in urinary Na+ raises the urinary water output in Addison's disease. K+ helps to retain water in the cells, whereas, plasma proteins do help to retain water in the body by their osmotic effects. Increase in urinary urea or excretion of glucose in urine increases osmotically the urinary loss of water (osmotic diuresis).

The general biological role of mineral salts and chemical elements in human organism:

- plastic role (mineral salts are included in a structure of bones, dens, cartilages, organic macromolecules etc.);

- osmotic pressure maintenance;- they are the constituents of buffer systems (bicarbonate and

phosphate buffer systems);- they are the constituents of the certain hormones,

coenzymes, enzymes active canters;- they take part in the formation of membrane potential.

Macro-, micro- and ultramicroelements. Macroelements - are those the contents of which in

organism is more than 10-2 % (P, S, Ca, Na, K, Mg) and day necessity is more than 100 mg per day.

The content of microelements in human body is from 10-2 to 10-5 % (I, F, Se, Co, Cu, Zn).

Ultramicroelements - are those the contents of which in organism is less than 10-5 % (Pb, Au, Mo and others).

Biological role of potassium and sodium. - potassium promotes the protein synthesis by ribosomes;- number of enzymes require K+ for maximum activity (for

example in the glycolitic sequence K+ is required for maximum activity of pyruvate);

metabolically supported gradients of Na+ and K+ across the cell membrane are involved in the maintenance of the membrane potential of excitable tissues, which is the vehicle for transmission of impulses in the form of an action potential;

K+ ions enhance the function of parasympathetic nervous system and acetylcholine action on the nervous terminals in muscles;

K+ ions reduce the exciting influence of ions on muscles;a proper plasma K+ level is essential for the normal heart

functioning more precisely for relaxation of myocardium

sodium ions play the main role in regulation of osmotic pressure and retention of water in an organism;

- sodium chloride of blood plasma is the main origin of hydrochloric acid formation;

- Na+ ions take part in the formation of a short-term memory.

Sodium content in blood plasma is 130-150 mmol/l.Potassium content in the blood is 3.4-5.3 mmol/l,

this is only 2 % of all potassium content in the human body.

Regulating of potassium and sodium metabolism

The main hormones, regulating Na+ metabolism, are mineralocorticoids and atrial natriuretic peptide (ANP). The mineralocorticoids, aldosterone and deoxycorticosterone, increase Na+ reabsorption from the tubular fluid and therefore their excess causes Na+ retention. In addition, these hormones increase the elimination of more K+ and Na+ in the urine.

A greater formation of aldosterone (primary aldosteronism or Conn’s syndrome) is associated with an increased Na+ retention in the body (hypernatriemia) with hypokaliemia and metabolic alkalosis. Conditions like congestive heart failure, cirrhosis of the liver and nephrotic syndrome also lead to a greater formation of aldosterone (secondary aldosteronism).

CHLORIDE MAJOR ANION OF ECF.

SECRETED IN GASTRIC JUICE

99% REABSORBED UNDER NORMAL PH CONDITIONS.

CHLORIDE SHIFT

DECREASED IN ACIDOSIS

BICARBONATEPRESENT IN ECF

BUFFERING ACTION

REABSORBED IN TUBULE AS CO2 FOR HYDROGEN ION.

Functions of calcium in the body:1. Calcium salts take part in bone and tooth development.

Deficient supply of calcium leads to rickets in children and osteomalacia in adults.

2. The clotting of blood needs calcium ions3. By regulating the membrane permeability calcium

ions control the excitability of nerves. 4. Calcium ions act as a cofactor or activator of certain

enzymes. A protein namely calmodulin is present within cells, which can bind calcium.

5. Calcium ions take part in the contraction of muscle including heart muscle and are involved in the excitation-contraction coupling mechanism.

6. Calcium ions are responsible for initiating contraction in vascular and other smooth muscles. Calcium ions enter through specific channels just as is the case with cardiac muscle.

7. Calcium is essential for maintaining the integrity of capillary wall.

8. Calcium ions are involved in exocytosis and thus have an important role in stimulus-secretion coupling in most exocrine and endocrine glands.

9. Some hormones exert their influence through Ca2+.

CALCIUM

• CALCITONIN- decreases bone resorption

Biological role of magnesium.- Half of magnesium occurs in the inorganic matter

of bones and the rest occurs in soft tissues and body fluids. Blood plasma contains 0.8-1.2 mmol/l of Mg.

- Nuts, legumes, chlorophyll and whole grains are very good sources of magnesium.

Functions of Mg in the body:1. It takes part in the formation of complex salts of

bones and teeth.2. It acts as a cofactor for many enzymes.3. It serves to decrease neuromuscular irritability. Effects of a high serum Mg2+ level -

Experimentally, a serum Mg2+ level of 8 mmol/l produces immediate and profound anesthesia and paralysis of voluntary muscles. These effects can be reversed by an intravenous injection of a corresponding amount of Ca2+. Serum Mg2+ tends to rise in renal failure.

Biological role of iron.

Iron is part of the structure of many important body constituents, e.g. hemoglobin, myoglobin, enzymes like cytochromes, catalase, xanthine oxidase, mitochondrial α-glycerophosphate oxidase, etc. The iron content of hemoglobin is 0.34%.

Dietary sources - Animal sources are the best and include liver, red meat and egg yolk. Of the vegetables, spinach and other leafy vegetables are good sources. Dried fruits also contain appreciable amounts of iron.

The role of vitamins and hormones in regulation of calcium metabolism.

The main hormones regulating Ca metabolism are calcitonin and parathyroid hormone.

Calcitonin is a hormone which is produced by the parafollicular cells (also called clear or C cells) of the thyroid gland. It lowers the plasma calcium level as it antagonizes the action of the parathyroid hormone. Calcitonin decreases bone resorption and increases the deposition of calcium in bones. It also increases urinary loss of Ca2+ by inhibiting the Ca2+ reabsorption in the proximal convoluted tubules.

Parathyroid hormone increases intestinal absorption of calcium, it also mobilizes bone calcium and causes a marked hypercalcemia. It also increases calcium absorption from the distal convoluted tubules of the kidney.

Active vitamin D greatly increases the absorption of calcium by increasing the amount of the specific transport protein responsible for active transport of calcium in the proximal small intestinal wall. Effect of parathyroid hormone is less marked than that of vitamin D; it is mediated through conversion of vitamin D to its active form.

Biological role of phosphorus An adult body contains 1 kg phosphate and it is found in

every cell of the body. Most of it (about 80%) occurs in combination with calcium in the bones and teeth. About 10% of body phosphorus is found in muscles and blood in association with proteins, carbohydrates and lipids.

Biochemical functions:- Phosphorus is essential for the development of bones and

teeth.- It plays a central role for the formation and utilization of

high-energy phosphate compounds (ATP, GTP, creatine phosphate etc.).

- Phosphorus is required for the formation of phospholipids, phosphoproteins and nucleic acids (DNA and RNA).

- It is essential component of several nucleotide coenzymes eg. NAD, NADP, pyridoxal phosphate, ADP, AMP.

- Several proteins and enzymes are activated by phosphorylation.

- Phosphate buffer system is important for the maintenance of pH in the blood as well as in the cells.

Regulation of Renal Phosphate Excretion

PTH play important role in regulating phosphate concentration through 2 effects:

1) PTH promotes bone resorption, thereby dumping large amounts of phosphate ions into the ECF from bones salts

2) PTH decreases the transport maximum for phosphate by the renal tubules

Role of vitamins and hormones in regulation of phosphorous metabolism

The hormones – calcitriol, parathyroid hormone and calcitonin are the major factors that regulate the plasma phosphorus within a narrow range (1.2-2.2mmol/l). Calcitriol is the biologically active form of vit.D. It acts at 3 different levels (intestine, kidneys and bone). Calcitriol increases the intestinal absorption of calcium and phosphate. Calcitriol along with parathyroid hormone increases the mobilization of calcium and phosphorus from bone.

Calcitriol is also involved in minimizing the excretion of Ca and P through the kidney, by decreasing their excretion and enhancing reabsorption. Calcitonin inhibits the reabsorption of phosphorus in kidneys. Thus, calcitonin decreases the phosphorus content in blood. Parathyroid hormone decreases serum phosphorus and increases urinary PO4 (increase phosphorus excretion in urine).

IodineThe total body contains about 20mg iodine, most of

it (80%) being present in the thyroid gland. The only known function of iodine is its requirement for the synthesis of thyroid hormone mainly thyroxin (T4) and triiodothyronin (T3).

Dietary requirements: 100-150micrograms per day. Sources: Sea food, drinking water, iodized salt. Diseases states: Toxic goiter.

FluorideFunctions: 1.It prevents the development of dental

caries. 2.It is necessary for the proper

development of bones . 3.It inhibits the activities of certain

enzymes.Dietary requirements: 1-2 mg per day.Sources: Drinking water.

CopperFunctions:- Its an essential constituent of several enzymes

(cytochrome oxidase, catalase, superoxide dismutase etc.)

- Its necessary for the synthesis of hemoglobin, melanin and phospholipids.

- Ceruplasmin has oxidase activity and thereby facilitates the incorporation of ferric iron into transferrin.

- Development of bone and nervous system (myelin requires Cu).

Dietary requirements:2-3 mg per day.Sources: Liver, kidney, meat, egg yolk, nuts and green

leafy vegetables.Disease status: - Copper deficiency (anaemia).- Menke’s disease (defect in the intestinal absorption of

copper).- Wilson’s disease

ZincFunctions:- It is an essential component of several enzymes

(carbonic anhydrase, alcohol dehydrase etc.) - The storage and secretion of insulin from the beta

– cells of pancreas requires zinc.- It is require for wound healing.- It is essential for the proper reproduction.Dietary requirements: 10-15g per day.Sources: Meat , fish, eggs, milk, nuts.Disease status:Zinc deficiency: poor wound healing, anaemia, loss

of appetite, loss of taste sensation

Cobalt Cobalt is only important as constituent of vit-B12.

The functions of cobalt is same as that of vit B12.Selenium

Functions:- Selenium along with vit E, prevents the development of

hepatic necrosis and muscular dystrophy.- Selenium is involved in maintaining structure integrity

of biological membranes.- Selenium prevents lipid peroxidation and protect the

cells against the free radicals.- Selenium binds with certain heavy metals and protects

the body from their toxic effects.Dietary requirements: 60-250micrograms.Sources: Liver, kidneys, seafood.Toxicity: Selenosis is a toxicity due to very excessive

intake of selenium. The manifestation of selenosis includes weight loss, emotional disturbances, diarrhea, hair loss and garlic odor in breath.

The biological role of chlorine and sulfur.

- Chlorine is contained in all biological liquids of the organism. - Cl- anions play important role in maintance of blood osmotic

pressure.- Cl- anions easily pass through the cell membranes (for example,

erythrocytes) and play important role in in maintenance of a constance and regulation of hydrogen ions concentration.

- Cl- anions also play important role in formation of stomach hydrochloric acid.

- In the organism sulfur exists both as organic and inorganic compounds.

- It is a component of sulfurs containing amino acids, proteins. A lot of sulfur is included into the connective tissue (epithelium, nails, hair). Sulfur is a constituent of some hormones (insulin, pituitary hormones), enzymes, coenzymes, peptide glutathione, bile acid (taurin). Like phosphorus sulfur takes part in formation of macroergic bounds. Sulfates form conjugates with different toxic substances in liver and then these conjugates are excreted from the organism. Thus sulfur executes the decontaminating function.

The role of vitamins and hormones in regulation of water-salt metabolism.

Vitamin D regulates the calcium homeostasis in organism. It stimulates the absorption of calcium ions in the intestine and renal canaliculus. Vitamin D increases the Ca2+ level in organism.

Aldosteron promote the sodium reabsorption in renal canaliculuses and excretion of potassium ions by kidneys and skin. Thus aldosteron results in hypernatriemia and hypokaliemia.

Na-diuretic hormone retards the reabsorption of Na in renal canaliculuses.

Calcitonin promotes the transition of calcium from blood in bones and inhibits the reabsorption of phosphorus in kidneys. Thus, calcitonin decreases the Ca and P contents in blood.

Parathyroid hormone promotes the transition of calcium from bones to blood; promotes the absorption of Ca in the intestine. Thus, parathyroid hormone increases the Ca amount in blood. Parathyroid hormone also inhibits the reabsorption of phosphorus in kidneys and decreases the P amount in blood.

Lipotropic hormone decreases the Ca amount in blood.Vasopressin - activates the hyaluronidase. This enzyme splits the

hyaluronic acid. The permeability of membranes is increased and reabsorption of water in kidneys is increased too. As result the day diuresis is decreased.

Insulin activates Na+, K+-ATP-ase (transition of K into the cells and Na from the cells).

Normal Laboratory Values

Parameters Values

Sodium 135-145 meq/L

Potassium 3.5-5.0 meq/L

Chloride 95-105 meq/L

Bicarbonate 22-28 meq/L

Calcium 9-11 mg/dL or 2.2-2.6mmo/l ( mmol/l*4 =mg/l)

Phosphate 3.2-4.3 mg/dL or 0.8-1.4 mmol/l (mmol/l*3=mg/l)

Glucose 70-110 mg/dL ( mg/dl/18 = mmol/dl)

BUN 8-18 mg/dL or 3.3-6.7mmol/l ( mmol/l* 6= mg/l)

Creatinine 0.6-1.2 mg/dL or 60-120 µmol/l (µmol/l* 0.011=mg/dl)

PLASMA Osmolality 280-295 mOsm/kg

URINE Osmolality 50-1200 mOsm/kg