kidney functions A WET BED . A – maintaining ACID-base balance W – maintaining WATER balance E – ELECTROLYTE balance T – TOXIN removal B – BLOOD Pressure control E –ERYTHROPOIETIN making D – Vitamin D metabolism.

FLUID, Electrolyte, and Acid-Base Balance

Introduction Electrolytes serve various purposes, such as conduction of electrical impulses along cell membranes in neurons and muscles, Stabilizing enzyme structures, and Releasing hormones from endocrine glands.

IONS IN PLASMA Contribute to the osmotic balance that controls the movement of water between cells and their environment. Imbalances of these ions can result in various problems in the body, and therefore their concentrations are tightly regulated.

HORMONES HAVE A VERY Important Role in This control ADH , Aldosterone and Renin/ angiotensin control the water and electrolytes balance and exchange between the renal filtrate and the renal collecting tubule. Calcium and phosphate are regulated by PTH, calcitrol, and calcitonin.

IMPORTANT ELECTROLYTES Electrolytes in living systems include sodium, potassium, chloride, bicarbonate, calcium, phosphate, magnesium, copper, zinc, iron, manganese, molybdenum, copper, and chromium. In terms of body functioning, six electrolytes are most important: sodium, potassium, chloride, bicarbonate, calcium, and phosphate.

Roles of Electrolytes These six ions help in nerve excitability, endocrine secretion, membrane permeability, buffering body fluids, and controlling the movement of fluids between compartments. These ions enter the body through the digestive tract. More than 90 percent of the calcium and phosphate that enters the body is incorporated into bones and teeth, with bone serving as a mineral reserve for these ions. In the event that calcium and phosphate are needed for other functions, bone tissue can be broken down to supply the blood and other tissues with these minerals. Phosphate is a normal constituent of nucleic acids high energy molecules, phosphate buffer system

Excretion of ions occurs mainly through the kidneys, with lesser amounts lost in sweat and in feces. Excessive sweating may cause a significant loss, especially of sodium and chloride. Severe vomiting or diarrhea will cause a loss of chloride and bicarbonate ions. Adjustments in respiratory and renal functions allow the body to regulate the levels of these ions in the ECF.

Fluid and Electrolyte Balance Fluids constitute ~50%–60% of total body composition in which Minerals are dissolved and forming electrolytes Fluid compartments Intracellular fluid (ICF) Extracellular fluid (ECF)

Body composition and Fluid Compartments Distribution of body solids and fluids in an average lean , adult female and male

Changes in Water Content with Age Water content-varies with gender, body mass and age. The percentage of body weight is composed of water. It is generally greater in men than women because men tend to have more lean body mass than women. Fat cells contain less water than an equivalent volume of lean tissue. One liter of water weights 2.2 lb (1kg). Therefore body weight change is an excellent indicator of overall fluid volume loss or gain. If a pt. D rinks 240 ml (8oz) there will be a weight gain of 0.5lb (0.24kg), an adult who is fasting might lose 1-2 lbs per day, most in fluids. Thus, infants and elderly are at a higher risk for fluid related problems than young adults

Body Fluid Compartments In lean adults, body fluids constitute 55% of female and 60% of male total body mass Intracellular fluid (ICF) inside cells About 2/3 of body fluid Extracellular fluid (ECF) outside cells Interstitial fluid between cell is 80% of ECF Plasma in blood is 20% of ECF Includes lymph, cerebrospinal fluid, synovial fluid, aqueous humor, vitreous body, endolymph, perilymph, and pleural, pericardial, and peritoneal fluids

Adult males Adult females Other body fluids (≤1%) Total body composition of adult males and females WATER 60% ECF ICF Intracellular fluid 33% Interstitial fluid 21.5% Plasma 4.5% Solids 40% (organic and inorganic materials) Other body fluids (≤1%) Adult males SOLIDS 40% WATER 50% ECF ICF Figure 24 Section 1.1 Fluid and Electrolyte Balance Intracellular fluid 27% Interstitial fluid 18% Plasma 4.5% Other body fluids (≤1%) Solids 50% (organic and inorganic materials) Adult females SOLIDS 50% 16

The solid components of a 70-kg (154-pound) individual with a minimum of body fat (31.5 kg; 69.3 lbs) Kg Figure 24 Section.1.2 Fluid and Electrolyte Balance Proteins Lipids Minerals Carbohydrates Miscellaneous 17

Daily Water Gain and Loss

Figure 24.1.1 Fluid balance exists when water gains equal water losses 19

Sources of Body Water Gain and Loss Fluid balance related to electrolyte balance Intake of water and electrolytes rarely proportional Kidneys excrete excess water through dilute urine or excess electrolytes through concentrated urine Body can gain water by Ingestion of liquids and moist foods (2300mL/day) Metabolic synthesis of water during cellular respiration and dehydration synthesis (200mL/day) Body loses water through Kidneys (1500mL/day) Evaporation from skin (600mL/day) Exhalation from lungs (300mL/day) Feces (100mL/day)

Regarding Cells ,the basic unit of life we know that Human cells dwell in salt water. Their well-being depends on the ability of the body system to regulate the salinity of ECF. By controlling water intake and excretion, the osmoregulatory system normally prevents the plasma sodium concentration from going outside its normal range (135 to 145 mmol per liter). Failure of the system to regulate within this range exposes cells to hypotonic or hypertonic stress.

The plasma sodium concentration affects cell volume. The term “tonicity” describes the effect of plasma on cells — Hypotonicity makes cells swell and ___Hypertonicity makes them shrink.

Fluid balance ICF and ECF compartments balance Vary in composition Are at osmotic equilibrium Loss of water from ECF is replaced by water in ICF = Fluid shift Occurs in minutes to hours and restores osmotic equilibrium Dehydration Results in long-term transfer that cannot replace ECF water loss Homeostatic mechanisms to increase ECF fluid volume will be employed

The major factors that affect ECF volume Water absorbed across digestive epithelium (2000 mL) Water vapor lost in respiration and evaporation from moist surfaces (1150 mL) ECF Metabolic water (300 mL) Water lost in feces (150 mL) ICF Water secreted by sweat glands (variable) Figure 24.1.3 Fluid balance exists when water gains equal water losses Plasma membranes Water lost in urine (1000 mL) 24

Mineral balance Mineral balance Equilibrium between ion absorption and excretion Major ion absorption through intestine and colon Major ion excretion by kidneys Sweat glands excrete ions and water variably Ion reserves mainly in skeleton

and ion excretion (primarily at the kidneys) Mineral balance, the balance between ion absorption (in the digestive tract) and ion excretion (primarily at the kidneys) Ion Absorption Ion Excretion Ion reserves (primarily in the skeleton) Ion absorption occurs across the epithelial lining of the small intestine and colon. Sweat gland secretions (secondary site of ion loss) Ion pool in body fluids Kidneys (primary site of ion loss) Figure 24.2.1 Mineral balance involves balancing electrolyte gains and losses ICF ECF 26

Figure 24.2.2 Mineral balance involves balancing electrolyte gains and losses 27

Water and sodium balance Sodium balance (when sodium gains equal losses) Relatively small changes in Na+ are accommodated by changes in ECF volume Homeostatic responses involve two parts ADH control of water loss/retention by kidneys and thirst Fluid exchange between ECF and ICF

The mechanisms that regulate sodium balance when sodium concentration in the ECF changes ADH Secretion Increases Recall of Fluids The secretion of ADH restricts water loss and stimulates thirst, promoting additional water consumption. Because the ECF osmolarity increases, water shifts out of the ICF, increasing ECF volume and lowering ECF Na concentrations. Rising plasma sodium levels Osmoreceptors in hypothalamus stimulated If one consumes large amounts of salt without adequate fluid the plasma Na concentration rises temporarily. HOMEOSTASIS RESTORED HOMEOSTASIS DISTURBED Decreased Na levels in ECF Increased Na levels in ECF HOMEOSTASIS Normal Na concentration in ECF Start Water balance depends on sodium balance, and the two are regulated simultaneously 29

The mechanisms that regulate sodium balance when sodium concentration in the ECF drops HOMEOSTASIS Start Normal Na concentration in ECF HOMEOSTASIS DISTURBED HOMEOSTASIS RESTORED Decreased Na levels in ECF Increased Na levels in ECF Osmoreceptors in hypothalamus inhibited Water loss reduces ECF volume, concentrates ions ADH Secretion Decreases Figure 24.3.1 Water balance depends on sodium balance, and the two are regulated simultaneously As soon as the osmotic concentration of the ECF drops by 2 percent or more, ADH secretion decreases, so thirst is suppressed and water losses at the kidneys increase. Falling plasma sodium levels 30

Water and sodium balance Sodium balance (continued) Exchange changes in Na+ are accommodated by changes in blood pressure and volume Hyponatremia (natrium, sodium) Low ECF Na+ concentration (<136 mEq/L) Can occur from overhydration or inadequate salt intake Hypernatremia High ECF Na+ concentration (>145 mEq/L) Commonly from dehydration

Water and sodium balance Sodium balance (continued) Exchange changes in Na+ are accommodated by changes in blood pressure and volume (continued) Increased blood volume and pressure Natriuretic peptides released Increased Na+ and water loss in urine Reduced thirst Inhibition of ADH, aldosterone, epinephrine, and norepinephrine release Decreased blood volume and pressure Endocrine response Increased ADH, aldosterone, RAAS mechanism Opposite bodily responses to above

The mechanisms that regulate water balance when ECF volume changes Responses to Natriuretic Peptides Combined Effects Increased Na loss in urine Reduced blood volume Increased water loss in urine Rising blood pressure and volume Natriuretic peptides released by cardiac muscle cells Reduced thirst Reduced blood pressure Inhibition of ADH, aldosterone, epinephrine, and norepinephrine release Increased blood volume and atrial distension HOMEOSTASIS RESTORED HOMEOSTASIS DISTURBED Figure 24.3.2 Water balance depends on sodium balance, and the two are regulated simultaneously Falling ECF volume Rising ECF volume by fluid gain or fluid and Na gain HOMEOSTASIS Start Normal ECF volume 33

The mechanisms that regulate water balance when ECF volume changes HOMEOSTASIS Start Normal ECF volume HOMEOSTASIS DISTURBED HOMEOSTASIS RESTORED Falling ECF volume by fluid loss or fluid and Na loss Rising ECF volume Decreased blood volume and blood pressure Endocrine Responses Combined Effects Increased renin secretion and angiotensin II activation Figure 24.3.2 Water balance depends on sodium balance, and the two are regulated simultaneously Increased urinary Na retention Decreased urinary water loss Increased aldosterone release Falling blood pressure and volume Increased thirst Increased ADH release Increased water intake 34

Potassium imbalance Potassium balance (K+ gain = loss) Major gain is through digestive tract absorption ~100 mEq (1.9–5.8 g)/day Major loss is excretion by kidneys Primary ECF potassium regulation by kidneys since intake fairly constant Controlled by aldosterone regulating Na+/K+ exchange pumps in DCT and collecting duct of nephron Low ECF pH can cause H+ to be substituted for K+ Potassium is highest in ICF due to Na+/K+ exchange pump ~135 mEq/L in ICF vs. ~5 mEq/L in ECF

The major factors involved in potassium balance Factors Controlling Potassium Balance Approximately 100 mEq (1.9–5.8 g) of potassium ions are absorbed by the digestive tract each day. Roughly 98 percent of the potassium content of the human body is in the ICF, rather than the ECF. The K concentration in the ECF is relatively low. The rate of K entry from the ICF through leak channels is balanced by the rate of K recovery by the Na/K exchange pump. When potassium balance exists, the rate of urinary K excretion matches the rate of digestive tract absorption. The potassium ion concentration in the ECF is approximately 5 mEq/L. Figure 24.4.1 Disturbances of potassium balance are uncommon but extremely dangerous KEY  Absorption The potassium ion concentration of the ICF is approximately 135 mEq/L. Renal K losses are approximately 100 mEq per day  Secretion  Diffusion through leak channels 36

The role of aldosterone-sensitive exchange pumps in the kidneys in determining the potassium concentration in the ECF The primary mechanism of potassium secretion involves an exchange pump that ejects potassium ions while reabsorbing sodium ions. Tubular fluid ECF The sodium ions are then pumped out of the cell in exchange for potassium ions in the ECF. This is the same pump that ejects sodium ions entering the cytosol through leak channels. KEY Figure 24.4.2 Disturbances of potassium balance are uncommon but extremely dangerous  Aldosterone- sensitive exchange pump  Sodium-potassium exchange pump 37

Distal convoluted tubule Events in the kidneys that affect potassium balance Under normal conditions, the aldosterone-sensitive pumps exchange K in the ECF for Na in the tubular fluid. The net result is a rise in plasma sodium levels and increased K loss in the urine. Distal convoluted tubule When the pH falls in the ECF and the concentration of H is relatively high, the exchange pumps bind H instead of K. This helps to stabilize the pH of the ECF, but at the cost of rising K levels in the ECF. Collecting duct Figure 24.4.3 Disturbances of potassium balance are uncommon but extremely dangerous 38

Potassium imbalance Disturbances of potassium balance Hypokalemia (kalium, potassium) Below 2 mEq/L in plasma Can be caused by: Diuretics Aldosteronism (excessive aldosterone secretion) Symptoms Muscular weakness, followed by paralysis Potentially lethal when affecting heart

Potassium imbalance Disturbances of potassium balance (continued) Hyperkalemia Above 8 mEq/L in plasma Can be caused by: Chronically low pH Kidney failure Drugs promoting diuresis by blocking Na+/K+ pumps Symptoms Muscular spasm including heart arrhythmias

THANKS

Sodium NA At.No. 11 Atomic mass 22.98

SODIUM Alkali metal Highly reactive, Found in combined state, mostly as Salt.

The body needs a small amount of sodium to help maintain normal blood pressure and normal function of muscles and nerves.

REQUIREMENT Estimated safe and adequate daily dietary intake Infants 0 – 0.5 yrs 115 – 350mg 0.5 – 1.0yr 250 – 750mg Children 1 – 3 yrs 325 – 975 4 – 6 yrs 450 – 1350 7 – 10 yrs 600 – 1800 11+ 900 – 2700 Adults 1100 – 3300

Infants requirement is low because of Small lean body mass Composition of feces Cutaneous losses Minimum requirement for infants and young children is about 58 mg/day.

Dietary sources Bread Cheese salad egg nuts spinach whole grain Table salt “NaCl”, added to food Bread Cheese salad egg nuts spinach whole grain In all foods even water. 2.5 grams of salt contain 1gm of Na

Human milk contains about 160mg/litre Cows milk contains about 483mg/litre

Absorption and Metabolism Sodium is readily absorbed from ileum Very little is excreted in feces except in diarrhea

Adults maintain sodium balance with little more than What is required by infant. Kidneys maintain its balance in blood (Homeostasis) under the influence of a hormone “Aldosterone” on renal tubules. When intake is decreased, aldosterone secretion Increases resulting in decrease of urinary excretion of sodium.

Sweat is another major route of Sodium loss 20-50mg/L

Distribution 1/3rd of Na is in inorganic portion of skeleton 2/3rd in ECF and is osmoticaly active (water soluble and exchangeable)

Contd. Total body content = 3800 – 4000 meqt (165 – 174 mg) ECF = 1750 meqt (76 mg) Soft tissues = 400 meqt (17.4 mg) Bone = 1850 meqt (80 mg)

Distribution in body / tissue Whole blood = 70 meqt/L (161 mg/dl) Plasma = 143 meqt/L (330 mg/dl) Cells = 37 meqt/L (85 mg/dl) Muscle tissue = 26 – 70 meqt/L (60 – 160 mg/dl) Nerve tissue = ~ 140 meqt/L (312 mg/dl)

Functions Major cation of ECF Regulates Acid base balance, in conjunction with Cl / HCO3 It maintains the osmotic pressure of body fluids and protects severe fluid loss from body. It preserves normal irritability of muscle and permeability of cells.

Ions Contributing to Resting Potential Sodium (Na+) Chloride (Cl-) Potassium (K+) Negatively charged proteins (A-) synthesized within the neuron found primarily within the neuron

The Neuron at Rest Ions move in and out through ion- specific channels K+ and Cl- pass readily Little movement of Na+ A- don’t move at all, trapped inside

Deficiency Diseases or Symptom When on normal diet  No hyponatermia Normal range in plasma is 135 – 145 meqt/L Hyponatermia is mostly secondary to Injury Illness (G/E) Burns Use of diuretics

Deficiency Diseases or Symptom Adrencorcortical insufficiency (Addison’s disease) Chronic Renal disease resulting in poor re-absorption of sodium Cirrhosis / CCF –  serum sodium level, without reduction in total body content of Na.

fall in tonicity as well as total volume of plasma Leading to Severe deficiency results in fall in tonicity as well as total volume of plasma Leading to Muscular cramps  Extremities and abdomen Headache Nausea Dry skin Reduce sweating Low urine out put having high specific gravity.

These are the conditions When Kidneys respond Complete re-absorption of filtered sodium Sodium excretion may fall to 20 meqt. / day or less.

Serum Sodium and adrenocortical function: Hypo-adrenalism 113 meq/L (Addison’s disease) Hyper-adrenalism 150 meq/L (Cushing syndrome) Normal 135 – 145 meq/L

Toxicity Diseases or Symptoms Hyper natremia may occur as a result of Rapid administration of sodium salt Hyper active adrenal cortex Administration of Cortisone or deoxy cortisone Dehydration excessive loss of water (Diabetes insipidus) May cause rise in blood pressure in susceptible individually.