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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
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


                       Body weight
                                          Volume (l)
   Compartment             (%)
        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
•   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
BICARBONATE
PRESENT 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 ions
3.    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.
• Calcium is essential for maintaining the integrity of
   capillary wall.
• Calcium ions are involved in exocytosis and thus have an
   important role in stimulus-secretion coupling in most
   exocrine and endocrine glands.
• 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).
Iodine
The 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.
                       Fluoride
Functions: 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.
Copper
Functions:
- 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
Zinc
Functions:
- 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

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Water minerals metabolism & kidney function

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  • 4. 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
  • 5. 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.
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  • 8. 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.
  • 9. 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).
  • 10. 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.
  • 11. 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.
  • 12. 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.
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  • 14. 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.
  • 15. 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.
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  • 17. Distribution of water in an adult man, weighing 70 kg Body weight Volume (l) Compartment (%) Total 60 42 ICF 40 28 ECF 20 14 Interstitial fluid 15 10,5 Plasma 5 3,5
  • 18. 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.
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  • 20. Regulation of Water Metabolism • 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).
  • 21. 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).
  • 22. 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
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  • 24. 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.
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  • 26. 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).
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  • 28. CHLORIDE MAJOR ANION OF ECF. SECRETED IN GASTRIC JUICE 99% REABSORBED UNDER NORMAL PH CONDITIONS. CHLORIDE SHIFT DECREASED IN ACIDOSIS
  • 29. BICARBONATE PRESENT IN ECF BUFFERING ACTION REABSORBED IN TUBULE AS CO2 FOR HYDROGEN ION.
  • 30. 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 ions 3. 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. • Calcium is essential for maintaining the integrity of capillary wall. • Calcium ions are involved in exocytosis and thus have an important role in stimulus-secretion coupling in most exocrine and endocrine glands. • Some hormones exert their influence through Ca2+.
  • 32. 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.
  • 33. 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.
  • 34. 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.
  • 35. 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.
  • 36. 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
  • 37. 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).
  • 38. Iodine The 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. Fluoride Functions: 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.
  • 39. Copper Functions: - 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
  • 40. Zinc Functions: - 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
  • 41. 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.
  • 42. 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.
  • 43. 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).
  • 44. 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