Disorders of water-electrolyte metabolism and acid-base homeostasis �

Goals:

• Consider the classification of water-electrolyte balance disorders and acid–base homeostasis

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• Find out the main pathogenetic mechanisms of disorders of hypo- and hyperhydria and acid–base homeostasis

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• Investigate the etiology and pathogenesis of CBS disorders and peripheral edema.

Water balance

The difference between the inflow (+ formation) of water and its excretion (+ loss) from body. What is the normal water balance? ..

• All the water of a healthy organism is divided into two sectors: intracellular - the cells contain ⅔ of all water (40% of body weight - water); extracellular - out of cells - ⅓ of all water (20% of body weight - water).
• Between them there is a constant exchange of water and dissolved substances in it through semipermeable membranes, representing processes of osmosis and diffusion which obey two laws: electroneutrality and isoosmolarity.

• Law of electroneutrality: if an ion is output from one sector, another ion with the same sign of charge will be introduced in its place.
• The law of isoosmolarity: the solvent (HPO) will move in such a direction as to equalize the osmolarity (osmotic pressure) in all sectors of the body.
• Osmosis is the spontaneous movement of a solvent through a semipermeable membrane from a less concentrated solution to a more concentrated one.
• Osmotic pressure is the pressure at which the solvent enters the solution through a semipermeable membrane.

Osmotic pressure is the driving force of water exchange between the cell and the extracellular fluid

• Determined by the concentration of osmotically active substances (electrolytes (sodium!), Glucose, urea)Normal:290 ± 10 mosmol / l

Starling mechanism: driving forces of water exchange between vessels and tissue fluid

Starling's law:

• in the initial part of a capillary the sum of hydrodynamic and hydrostatic pressure prevails over oncotic and exceeds hydrostatic pressure in tissue therefore liquid from initial department of a capillary passes to tissue;
• in the middle part of the capillary, the pressure equalizes and the movement of fluid stops;
• at the venous end the sum of the hydrostatic, hydrodynamic and oncotic pressure of the plasma becomes less than the same amount in the tissues, and therefore the fluid passes from the intercellular space into the capillary.

Regulation mechanisms of water-electrolyte balance

• Antidiuretic hormone (vasopressin) Aldosterone (as a component of the renin-angiotensin-aldosterone system) Na-uretic hormone of the atria
• Behavioral changes (thirst)

Etiology of extracellular hypohydria (dehydration):

• ISOSOMOLAR: acute blood loss, burn disease
• HYPEROSMOLAR: prolonged vomiting, diarrhea, hypersalivation, profuse sweating, hyperventilation, polyuria with chronic renal failure, diabetes mellitus and diabetes insipidus
• HYPOOSMOLAR: Addison's disease (hypoaldosteronism), use of salt diuretics, polyuria with acute renal failure

Dehydration signs

Etiology of extracellular hyperhydria:

• ISOSOMOLAR: excessive introduction of isotonic NaCl solution
• HYPEROSMOLAR: secondary hyperaldosteronism (heart, liver failure, renal failure in the stage of oligoanuria), excessive administration of hypertonic electrolyte solutions
• HYPOOSMOLAR (water poisoning): Parkhon's syndrome (excess vasopressin), excessive administration of hypotonic electrolyte and glucose solutions

• Water accumulation in tissue (in the intercellular space) - edema (oedema)
• Water accumulation in the cavities - hydrops: ascites, hydropericardium, hydrothorax, etc.
• Edematous fluid (except in case of inflammation) - transudate!

Signs of hyperhydria:

Swelling of cells:

• Intracellular hyperhydria
• Cause: hypoosmolar condition of the extracellular environment – HYPONATREMIA The most dangerous - swelling of brain cells!

Cell shrinkage:

• Intracellular hypohydria
• Cause: hyperosmolar condition of the extracellular environment – HYPERNATREMIA The most dangerous -shrinkage of brain cells!

Classification of peripheral edema

• BY ETIOLOGY: cardiac, renal, hepatic, inflammatory, allergic, toxic, "hungry".
• BY PATHOGENESIS: hydrostatic, oncotic, lymphogenic, membranogenic, myxedematous
• Based on - STARLING MECHANISM!

CONCLUSIONS:

• Water - a physiological solvent and is 60% of body weight! Maintaining the total volume of water and the substances dissolved in it (which determine the osmotic pressure!) Is an extremely important indicator of homeostasis!
• All disorders of WES (water-electrolyte share) are divided into intracellular and extracellular, among which they are divided into HYPERHYDRIA and HYPOHYDRIA.
• There are 5 main mechanisms of peripheral edema: hydrostatic, oncotic, lymphogenic, membranogenic, muxedematous.

Communication between WES and ABH

consists in the interaction of the laws of electroneutrality and isoosmolarity in environments separated by a semipermeable membrane through which NGOs freely penetrate and through which some ions are retained. The osmolarity of the extra- and intracellular sectors remains the same, but it is due to different ions, and that is why a negative charge occurs in the cell.

Acid–base homeostasis-�

• Balance between acids (proton donors) and bases (proton acceptors)

The chemical bases of ABH

• ABH is an integral part of WES, because ABH is a state of exchange of a single electrolyte (H +), which is the nucleus of the atom H⁺, deprived of its electron, proton - this is a very aggressive particle, because it seeks to regain the electron, taking it away other atoms, oxidize them). Therefore, the constant concentration of protons in the water sectors is very important for the body, especially since every 3 seconds a lethal number of protons is formed, which must be neutralized in time.

• The source of free protons are substances that can give them away by dissociation. Such substances are called acids.
• Acid is a substance capable of releasing hydrogen ions (proton donor).
• Base is a substance capable of binding hydrogen ions (proton acceptor).
• Alkali is a substance capable of releasing hydroxyl ions (OH⁻ ion donor).

• The concentration of protons is expressed by the indicator pH (from the English. Powerhydrogen - the strength of hydrogen) - the negative decimal logarithm of the concentration of H⁺ in solution.arterial blood pH 7.36 - 7.44.

Maintaining mechanisms of ABH

1. Buffer systems (mixture of weak acid or weak base with their salts): Bicarbonate buffer system- represented H₂CO3 / NaHCO3, having a total ion HCO3⁻, 1:20. Maintains a constant pH in blood plasma and intercellular fluid. Mechanism of action: ↑ Н⁺ (↓ pH) - neutralized by the alkaline component of the buffer → ↑ Н₂СО3 → СО₂ → stimulates the respiratory center → hyperventilation, and excess СО₂ is removed from the blood with exhaled air.

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• Phosphate buffer system- is represented by acidic (NaH₂PO4) and alkaline (Na₂HPO4) sodium salts of phosphoric acid in a ratio of 1: 4; supports CBS in the kidneys.
• Protein buffer system - represented by plasma proteins, Hb and intracellular fluid proteins; provides maintenance of stability of intracellular pH.

• . Hemoglobinogenic - is represented by redox of Hb and potassium salt of oxidized Hb.
• The oxidized form of Hb is a stronger acid, and it ↑ receipt from erythrocytes to the plasma of H⁺ ions.
• The reduced form of Hb is a weaker acid, and it has the ability to bind a large number of H⁺ ions.

In the vessels of the microcirculatory tract of the great circle of blood circulation, oxidized Hb gives O₂ to the tissues, and CO₂ enters the erythrocytes, which under the influence of carbonic anhydrase interacts with НОО → Н₂СО3, which dissociates, and the formed H⁺ ions combine with Hb.

2. External respiration system - ensures the stability of pCO₂ art. blood.

Excess H⁺ (↓ pH) → hyperventilation → ↓ СО₂ → ↓ H₂CO3 → hypocapnia. Lack of Н⁺ (↑ pH) → hypoventilation → ↑ СО₂ → ↑ H₂CO3 → hypercapnia.

In the capillaries of the lungs (small circle), CO₂ is released due to the transition of Hb to oxyhemoglobin, which, being a stronger acid, displaces CO₂ from sodium bicarbonate.

3. Kidneys:

-Acidogenesis - the formation and secretion into the lumen of the tubules of H⁺.

-Ammoniogenesis is the process of formation of ammonia from glutamine in nephrocytes, which is secreted in the urine in exchange for reabsorbed Na ⁺.

-Bicarbonate reabsorption (↑ alkaline plasma reserve) - is carried out in the proximal tubules of the nephrons.

Hydrocarbonate reabsorption in kidneys

• 4. Liver and gastrointestinal tract
• When there is an excess of acids in the liver, they are neutralized by deamination and the synthesis of urea is inhibited → ammonia neutralizes acids and ↑ excretion of am. salts with urine. When alkalining - urination ↑, ammoniogenesis weakens as a manifestation of the mechanisms of renal compensation.
• Pancreas secretes HCO3⁻ ions. Excess acids in the intercellular fluid - inhibits secretion; lack of acids → increased formation of bicarbonate ions.
• The stomach inhibits the secretion of HCl during alkalinization, and increases during acidification.

Indicators of acid–base homeostasis�

• pH art. blood 7.36 - 7.42 pCO₂ art.
• blood 36 -44 mm Hg
• SB standard bicarbonate 20 -26 mmol / l
• BB buffer bases 42-52 mmol / l
• BE (base excess) - shift of buffer bases ± 2 mmol / l

Forms of acid-base homeostasis imbalance

acidosis

• pathological condition characterized by a shift of pH to the acidic side (↓ 7.35).

alkalosis

• pathological condition with a shift of ABH in the alkaline direction (↑ 7,44).

Acidosis and alkalosis can be compensated and decompensated. Depending on the mechanisms of development - gas and non-gas.

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Hypoventilation → ↑ pCO2 ↑ 40 mm Hg. Art. → gas acidosis.

Hyperventilation - ↓ pCO2 → gas alkalosis

Accordingly: ↓ concentration of bicarbonate in blood plasma ↓ 24 mEq / l → non-gaseous acidosis,

and in the case of primary ↑ bicarbonate content - non-gaseous alkalosis.

ALL CATIONS AND ANIONS ARE DIVIDED INTO:

- fixed (their content changes only in the case of flow or excretion from the body: Na +, K +, Ca2 +, Mg2 +, Cl-, HPO42-, etc.);

• semi-fixed (formed and metabolized in the process of metabolism of carbohydrates, fats and proteins at low speed - NH4 +, lactate, pyruvate, ketone bodies, proteins);
• unfixed (formed and disappear in the process of metabolism almost instantly - bicarbonate and NH).

If the content of H⁺ in biological fluids is determined by the state of buffer systems, in particular, hydrocarbonate buffer, the concentration of HCO3⁻ is determined by the ratio of fixed and semi-fixed cations and anions.

Excess of cations - in particular Na⁺, - ↑ content of bicarbonate and lack of cations - ↑.

Conclusion:

non-gaseous acidosis occurs due to ↓ of hydrocarbons content caused by ↓ the ratio between fixed cations and anions, and non-gaseous alkalosis occurs due to ↑ hydrocarbonate caused by the fixed ratio of cations and anions.

Gas acidosis

• Shortness of breath (hypoventilation) Inhalation of a mixture with a high content of CO2→ ↑ СО₂ in blood.
• Compensatory reactions are aimed at ↑ plasma bicarbonate concentrations, and are provided by the kidneys. Acidogenesis increases.

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Non-gaseous acidosis (↓ bicarbonate in blood plasma)

• Metabolic (type 1 diabetes, hypoxia, burns, starvation, gout, renal failure, CO poisoning)
• Exogenous (long-term use of acidic foods, opiate / barbiturate poisoning, myasthenia gravis, pneumonia, pulmonary edema)
• Excretory (renal and digestive disorders).

Compensatory reactions in non-gaseous acidosis.

External respiration system: ↑ conc. Н⁺ → excitation of breath. center → hyperventilation → ↑ excretion of CO2 from the body.

Renal mechanisms: ↓ pH → activation of acidogenesis in the distal tubules → urine bicarbonate is stored in the body and urine pH ↓ → acidification of urine.

Gas alkalosis

• Lung hyperventilation (brain swelling, encephalitis, fever, altitude sickness, inadequate performance of artificial ventilation).
• Compensatory reactions are aimed of ↓ concentration of bicarbonate in plasma and is provided by kidneys.
• At ↓ рСО₂ of blood ↓ acidogenesis → ↑ pH of urine and ↓ bicarbonate in plasma.

Non-gaseous alkalosis (↑ blood bicarbonate)

• Excretory: hypochloremic (irrepressible vomiting); hypokalemic (hyperaldosteronism).

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• Exogenous (hypernatremic) - excessive salt intake. Compensatory reactions are aimed at ↑ pCO₂ in blood and are provided by the external respiratory system.

Conclusions:

Mechanisms of body protection from changes in pH consist of chemical buffers, as well as respiratory, renal and other mechanisms. They all function simultaneously to maintain a normal pH and are interdependent.

• Plasma bicarbonate is regulated mainly by the kidneys, while the partial voltage of arterial blood pCO2 is regulated by the lungs.

Used literature:

• Pathophysiology: a textbook, ed. M.N.Zayka, Y.V. Buzya, М.В. Crystal - 4 editions,
• 2014Pathophysiology: Tome 1 - textbook, ed. О.В. Ataman, 2012Robbins Basic Pathology - 10 Ed.,
• 2017.Sue E. Huether, Kathryn L. McCance: Understanding Pathophysiology - 6 Ed., 2017.
• Kamel S. Kamel, Mitchell L. Halperin - Fluid, Electrolyte and Acid-Base Physiology, 2017.Silbernagl S., Lang F. - Color Atlas of Pathophysiology, 2000.