Fluid, Electrolyte, & Acid-Base Balance

Total Body Water (TBW)

~ 60% of body weight
- Baby: 75%
- Men: 55-60%
- Women slightly less due to adipose tissue (nearly free of water)
- Obese People: 45%

Young adult male: 40L

Fluid Compartments

Areas separated by selectively permeable membranes and differing in chemical composition.

65% Intracellular fluid (ICF)

35% Extracellular fluid (ECF)
- 25% tissue (interstitial fluid)
- 8% Blood plasma/lymph
- 2% Transcellular fluid (CSF, peritoneal, pleural, and pericardial fluids; vitreous and aqueous humors of the eye; bile; and fluid in the digestive, urinary, and respiratory tracts)

Fluid Exchange

Exchanged between compartment by way of capillary walls and plasma membranes.
1) Osmosis: digestive tract → bloodstream
2) Capillary Filtration: blood → tissue fluid
- From tissue fluid it may be reabsorbed by capillaries, osmotically absorbed into cells, or taken up by the lymphatic system.

Osmotic gradients between ICF and ECF

Osmosis restores water balance so that osmolarity is equal in ICF and ECF.

Fluid Balance

- When daily gains and losses are equal.
- We gain and lose ~ 2500 mL/day

Fluid Imbalance

Occurs with abnormalities of total water volume, concentration or distribution.

Water Gains comes from 2 sources:

1) Metabolic Water:
- 200 mL/day
- By-product of dehydration synthesis reactions and aerobic respiration
2) Performed Water:
- Ingested water from food + drink
- 2300 mL/day

Water Loss

- Urine: 1500 mL/day
- Feces: 200 mL/day
- Expired breath: 300 mL/day
- Sweat: 100 mL/day by resting individualizing;
- Cutaneous Transpiration: 400 mL/day, evaporation of water from the epidermis that is not sweat.

Respiratory Loss

Energy lost to the environment as heat when organisms respire.
- Increases in cold weather → cold air is drier → absorbs more water from the respiratory tract.
- Decreases in hot/humid water but increases perspiration.

Insensible Water Loss

Loss of water through the breath and cutaneous sensation that we are not aware of.

Sensible Water Loss

Noticeable loss of water through urine and sweating.

Obligatory Water Loss

Water loss that is unavoidable → expired air, cutaneous transpiration, sweat, fecal moisture, and the minimum urine output
- About 400 mL/day needed to prevent azotemia

Azotemia (uremia)

High levels of nitrogenous waste in blood.

Fluid Intake

Regulated by thirst

Dehydration

- Decreases blood volume and blood pressure
- Increases blood osmolarity.

Osmoreceptors

Group of neurons in hypothalamus that respond to angiotensin II and rising osmolarity of ECF → indicate dehydration.
- Communicate with other hypothalamic neurons and produce ADH → promotes water conservation
- Communicate with cerebral cortex → produce sense of thirst

Thirst → Salivation

Thirst → conscious desire for water → leads to less salivation because:
1) Osmoreceptor response leads to sympathetic output from the hypothalamus that inhibits the salivary glands.
2) Saliva is produced by capillary filtration. During dehydrated, this is opposed by the lower capillary blood pressure and higher osmolarity of the blood

Cooling and moistening of the mouth

Rats drink less water when it's cooler than warm. Moistening the mouth temporarily satisfies thirst even if before it reaches the stomach.

Distention of stomach and small intestine

Inhibits thirst
- If a dog is allowed to drink water but its stomach is filled with food, thirst is satisfied for a time.
- If the water is drained away but the stomach is not inflated, satiation of thirst doesn't last as long.

Regulation of Water Output

Controlled via variaions in urine volume.

Kidneys

- Cannot completely prevent water loss or replace lost water/electrolytes
- Never fully restore fluid volume or osmolarity
- But in dehydration they can support existing fluid levels and slow down water loss and until water + electrolytes are ingested.

Urine Volumes → Sodium

Affected by the amount of sodium reabsorbed by the renal tubule.
- As Na+ is reabsorbed or secreted, equal amounts of water accompany it.

Urine Volumes → ADH → Dehydration

- Controls water output independently of sodium. Provides negative feedback loop.
Dehydration:
- Decrease in blood volume and Na+ concentration → increases osmolarity of blood → stimulates hypothalamic osmoreceptors → stimulate posterior pituitary to release ADH → stimulates cells of the collecting duct to make more aquaporins → kidneys reabsorb more water/produce less urine

Urine Volumes → ADH → High BV/BP + Low Osmolarity

If blood volume and pressure are high and osmolarity is low:
- ADH release is inhibited
- Renal tubules absorb less water
- Urine output increases
- Total body water declines.
- Ratio of water to sodium is increased, raising the Na+ concentration and osmolarity of blood

Fluid Deficiency

When water output exceeds water input over a long period of time.
2 kinds of deficiency:
1) Volume Depletion
2) Dehydration

- Differ in the relative loss of water + electrolytes and the resulting osmolarity of the ECF.

Volume Depletion → Hypovolemia

Occurs when propionate amounts of water & sodium are lost without replacement.
- TBW declines but osmolairty remains normal.
- Occurs in cases of hemorrhage, severe burns, & chronic vomitting/diarrhea.

Dehydration → Negative Water Balance

- Occurs when the body eliminates more water than Na+ → ECF osmolarity rises.
- Most commonly caused by lack of drinking water
- Additional causes → Diabetes mellitus, ADH hyposecretion (diabetes insipidus), profuse sweating, and overuse of diuretics.

Forms of Diabetes

Type 1
Type 2
Gestational
Insipidus

Type 1 Diabetes mellitus

- Total lack of insulin production
- Usually develops in childhood
- Insulin replacement therapy required

Type 2 Diabetes mellitus

Body produces insufficient insulin or is insulin resistance.

Diabetes Insipidus

- Not related to type 1 or 2
- Condition that causes an imbalance of fluids in the body
- Characterized by frequent urination and extreme thirst
- Insufficient production of ADH

Gestational Diabetes Mellitus (GDM)

- Dvelops during pregnancy in women who have not previously had diabetes.
- Charecterized by insulin resistance.

Dehydration → Infants vs. Adults

Infants are more venerable to dehydration because:
1) Need to excrete more water to eliminate toxic metabolites faster due to their higher metabolic rate
2) Kidneys are not fully mature and cannot concentrate urine as effectively
3) Greater ratio of body surface to volume → lose 2x as much water per Kg of body weight by evaporation.

Serious Effects of Fluid Deficiency

- Circulatory shock: due to loss of BV
- Neurological dysfunction: due to dehydration of brain cells
- Infant mortality: Usually caused by diarrhea

Volume Excess

Fluid excess in which sodium & water are retained and the ECF remains isotonic.
- Can result from aldosterone hyper secretion or renal failure

Hypotonic Hydration

AKA water intoxication or positive water balance.
- More water than sodium is retained and the ECF becomes hypotonic
- Occurs when water and salt is lost through urine and is replaced by drinking plain water.
- Lack of electrolytes
- Water dilutes ECF causing cellular swelling.
- May lead to life threatening condition of pulmonary/cerebral edema and death.

Fluid Sequestration

- Excess fluid accumulates in a particular location
- Edema

Edema

Accumulation of fluid in the interstitial spaces → tissue swelling

Plueral Effusion

Edema characterized by fluid accumulation in the pleural cavity due to infection.

Electrolytes

Create electrical potential across cell membranes
- Salts that exist as diatomic molecules (NaCl), not as free ions.

Major Cations of ECF

- Na+
- K+
- Ca2+
- Mg2+
- H+

Major Anions of ECF

- Cl-
- HCO3-
- Phosphates

Blood Plasma

Most accessible fluid for measurements of electrolyte concentration.

Sodium

- Effects membrane potential of cells
- Depolarizes nerves and muscles to trigger action potentials
- Accounts for 90-95% of osmolarity in ECF.
- Most significant solute in determining TBW.
- Creates gradient across plasma membrane that provides energy for the cotransport of glucose, potassium, and calcium.
- Na+-K+ pump generates body heat.
- Sodium bicarbonate buffers pH of ECF.

Sodium Intake

Adult needs 0.5 g/day.

Aldosterone

"Salt-retaining steroid hormone"
- Directly secreted by adrenal cortex due to hyponatremia and hyperkalemia.
- Indirectly secreted due to hypotension.
- Receptors found in acceding limb, DCT, and cortical part of CD.
- Binds to nuclear receptors → activates gene transcription for Na+-K+ pump → tubules reabsorb more Na+ (Cl- + water follow) and secrete more K+.
- Has little effect on Na+ plasma concentration, urine volume, blood volume and blood pressure due to the tendency of water to follow sodium osmotically.

Hypertension

- High BP inhibits the renin-angiotensin- aldosterone mechanism causing sodium loss.
- Almost no sodium is reabsorbed beyond the PCT

ADH

- Modifies water excretion independently of sodium excretion.
- Effects Na+ plasma concentrations (unlike aldosterone).
- Secreted by posterior pituitary gland in response to high Na+ levels.
- Causes kidneys to reabsorb more water.

Natriuretic Peptides

Secreted by atrial myocardium of the heart in response to high blood pressure
- Inhibit sodium and water reabsorption
- Inhibit secretion of renin and ADH.
- Causes kidneys to climates more sodium and water.
- Blood pressure is lowered.

Angiotensin II

- Increases BP by stimulating the constriction of precapillary arterioles
- Increases sodium reabsorption by activating the Na+-H+ antiport in the PCT.

Estrogen

- Mimics the effects of aldosterone.
- Causes women to retain water (through reabsorption of sodium) during menstrual cycle.

Progesterone

-Reduces sodium reabsorption.
- Diuretic effect.

Hypernatremia

- Excess sodium in blood plasma >145 mEq/L
- May result from administration of IV saline.
- Results in eater retention, hypertension, and edema.

Hyponatremia

- Deficient sodium in blood plasma

Potassium

- Most abundant cation in ICF
- Greatest effect on intracellular osmolarity and cell volume.
- Triggers action potential of nerves and muscles.
- Na+-K+ pump generates body heat.
- Essential cofactor for protein synthesis.

Potassium Homeostasis

- Closely linked to that of sodium
- 90% of K+ in GF is reabsorbed by the PCT
- Aldosterone stimulates renal secretion of K+.
- Potassium imbalances are the most dangerous of all electrolyte imbalances.

Potassium Homeostasis → Aldosterone

- Responds to high K+ concentrations.
- Stimulates the secretion of K+ and reabsorption of Na+.
- The more sodium there is in the urine, the less potassium, and vice versa.

Hyperkalemia

Excessive potassium in the blood

Hyperkalemia → Fast Onset

- Crush injury or hemolytic anemia releases large amounts of potassium from ruptured cells into ECF.
- Blood transfusion with outdates blood in which K+ leaks from RBC's into plasma.
- Sudden increase in K+ ECF level makes nerve + muscles cells very excitable.
- May result in cardiac arrest.

Hyperkalemia → Slow Onset

- May be caused by aldosterone hyposecretion, renal failure, or acidosis.
- Slow onset causes nerve + muscles cells to be less excitable.

Hypokalemia

Deficiency of potassium in the blood.
- Rarely results from dietary deficiency
- May occur from excessive sweating, vomiting, diarrhea, laxatives, aldosterone hypersecretion, or alkalosis.
- A decline in K+ in ECF moves more K+ from ICF to ECF → cells become hyper polarized and nerve and muscle cells are less excitable.
- Muscle weakness and tone, depressed reflexes, and irregular electrical heart activity.

Chloride

- Most abundant anion in ECF.
- Major contributor to blood osmolarity.
- Required for the formation of HCL in stomach.
- Involved in chloride shift that accompanies CO2 loading/unloading in RBCs.
- Play major role in regulation of body pH.

Chloride Homeostais

Cl- ions are strongly attracted to Na+, K+, and Ca2+.
- Homeostasis is achieved as a side effect of sodium homeostasis.
- Passively follows Na+ excretion or retention.

Hyperchloremia

- Excess chloride in the blood.
- Result of dietary excess or IV saline.

Hypochloremia

- Deficiency of chloride in blood
- May be a side effect of hyponatremia, hyperkalemia, or acidosis.

Calcium

- Strength for skeleton
- Activates the sliding filament mechanism of muscle contraction
- 2nd messenger for some hormones/neurotransmitters
- Exocytosis of neurotransmitters
- Essential factor in blood clotting
- Cells maintain low ICF levels

Calsequestrin

- Stores calcium in the sarcoplasmic reticulum and keeps it chemically unreactive.
- Cells maintain low Ca2+ levels because they have a high concentration of phosphate.
- If both were concentrated in the cell, calcium phosphate crystals would precipitate in the cytoplasm.

Calcium Homeostasis

- Regulated by calcitriol (children), calcitonin, and parathyroid hormone.
- Effects on bone deposition and reabsorption.
- Intestinal absorption and urinary secretion.

Hypercalcemia

- Excessive calcium in the blood
- May result from alkalosis, hyperparathyroidism, or hypothyroidism.
- Reduces Na+ permeability of plasma membranes and inhibits depolarization of nerve and muscle cells.
- Muscle weakness, depressed reflexes, and cardiac arrhythmia.

Hypocalcemia

- Deficient calcium in the blood - Can result from vitamin D deficiency, diarrhea, pregnancy, lactation, acidosis, hypoparathyroidism, or hyperthyroidism.
- Increases Na+ permeability of plasma membranes.
- Causes nerves/muscles to be overly excitable.
- Tetany, laryngospasm and suffocation.

Magnesium

- 54% is in bone tissue
- 45% in ICF (especially skeletal muscles)
- Most is complexed with ATP
- Necessary cofactor for enzymes, transport proteins, and nucleic acids.

Magnesium Homeostasis

- 30-40% is absorbed by small intestine. The rest is passed in feces.
- Intestinal absorption is regulated by vitamin D.
- 70% is reabsorbed by by thick segment of ascending limb via the paracellular route (between tubule epithelial cells)
- Parathyroid hormone covers rate of reabsorption.

Hypomagnesemia

- Plasma magnesium deficiency
- May be due to intestinal malabsorption, vomitting, diarrhea, or renal disease.
- Muscle tremors, spasms, or tetanus.
- Excessive vasoconstriction, tachycardia, ventricular arrhythmia.

Hypermagnesemia

- Excess of magnesium in the blood plasma.
- Rare except in renal insufficiency.
- Sedative effect, lethargy, muscle weakness, and weak reflexes.
- Respiratory depression or failure.
- Hypotension due to lack of vasomotor tone.
- Diastolic cardiac arrest.

Phosphates

- Equilibrium misture of phosphate, monohydrogen phosphate, and dihydrogen phosphate.
- Concentrated in ICF.
- Generated by the hydrolysis of ATP.
- Component of nuclei acids, phospholipids, ATP, GTP, cAMP, & creatine phosphate.
- Activate metabolic pathways by phosphorylating enzymes and substrates.
- Important buffers that stabilize pH.

Phosphate Homeostasis

- Found in food, absorbed by small intestine.
- PTH increases excretion due to its mechanism for increasing the concentration of calcium ions in the ECF.
- Homeostasis is not too critical.

The pH of a solution is determine by

The concentration of Hydrogen ions (H+).

Strong Acid

- An acid such as HCL that ionizes completely
- Gives up most of its hydrogen ions.
- Lowers the pH of a solution.

Weak Acid

- Sliglyly ionizes
- Keeps most hydrogen chemically bound.
- Does not effect pH too much.
- Carbonic acid (H2CO3)

Base

Any compound that accepts hydrogen ions (H+)

Strong Base

- Such as the hydroxide ion (OH-)
- Strong tendency to bind H+
- Raises pH

Weak Base

- Such as the bicarbonate ion (HCO3-)
- Binds less of the available H+
- Less effect on pH

Buffer

Any substance that resist changes in pH converting a strong acid or base to a weak one.

Physiological Buffers

Is a system, usually the respiratory or urinary system, that stabilizes pH by controlling the body's output of acids, bases, or CO2.
- Urinary system buffers the greatest quantity of acid or base but requires several hours.
- Respiratory system exerts effects within minuets but has less of an effect on pH.

Chemical Buffers

- A substance that binds or releases H+ from solutions when its concentration is too high or low.
- Can restore pH within a fraction of a second.
- Function as mixtures called buffer systems.

Buffer Systems

- Mixture of chemical buffers composed of a weak acid or base that can restore normal pH.
- The amount of acid/base that can be neutralized depends on the concentration of the buffers and the pH of their working environment.

3 Major Chemical Buffer Systems

1. Bicarbonate buffer system
2. Phosphate buffer system
3. Protein buffer system

The Bicarbonate Buffer System

Carbon dioxide reacts with water to form carbonic acid, which in turn rapidly dissociates to form a bicarbonate ion and a hydrogen ion.
- Optimal pH of system is 6.1
- Reversible Reaction
- When it proceeds to the right, carbonic acid acts as a weak acid by releasing H+ and lowering pH .
- When it proceeds to the left, bicarbonate acts as a weak base by binding H+ and raising pH.

The Phosphate Buffer System

- Proceeds to the right to release H+ and lower pH
- Proceeds to the left to bind H+ and raise pH
- Optimal pH of system is 6.8
- Most important in renal tubules and ICF where phosphates are more concentrated.

The Protein Buffer System

- Proteins are more concentrated than bicarbonate or phosphate buffers, especially in the ICF.
- Accounts for 3/4 of all chemical buffering in body fluids.
- Carboxyl or amino side groups of amino acids release H+ when pH rises, thus lowering pH.

Respiratory Control of pH

- Effects pH of body fluids by adjusting the rate/depth of breathing.
- Works through bicarbonate buffer system through the addition or removal of CO2.
- Adding CO2 raises H+ concentration and lowers pH.
- Removing CO2 lowers H+ concentration and increases pH.
- Rising CO2 and falling pH stimulates peripheral and central chemoreceptors which respond by increasing pulmonary ventilation.
- A drop in H+ concentration raises pH and reduces
pulmonary ventilation allowing CO2 to accumulate in the ECF faster than it is expelled.

Renal Control of pH

- Kidneys neutralize more acid/base than the respiratory system or chemical buffers.
- Do so by varying the amount of acid eliminated in urine.
- Renal tubules secrete H+ in tubular fluid where it binds to bicarbonate, ammonia, and phosphate buffers and is releases in urine.
- Kidneys may also expel unbound free H+ in urine (other buffer systems may only expel H+ if it is bound).

Acidosis

A pH below 7.35
- Makes resting membrane potential more negative
- Nerve and muscle cells are more difficult to stimulate.
- Depresses the central nervous system and causes confusion, disorientation, and coma.

Alkalosis

A pH above 7.45
- Makes resting membrane potential more positive.
- Neurons fire spontaneously and overstimulate skeletal muscle
- Muscle spasms, tetanus, convulsions, or respiratory paralysis.

2 Categories of Acid-Base Balance

1) Respiratory
2) Metabolism

Respiratory Acidosis

- A drop in blood pH due to lowered alveolar ventilation and a resulting accumulation of CO2 in the ECF
- Occurs in emphysema in which there is a severe reduction in the number of functional alveoli.

Respiratory Alkalosis

A rise in blood pH due to hyperventilation in which CO2 is eliminated faster than it is produced.

Metabolic Acidosis

A drop in pH of blood and body tissues as a result of increased production of organic acids:
- Lactic acid in anaerobic fermentation
- Ketone bodies in alcoholism and diabetes mellitus
- Can result from excessive ingestion of acidic drugs such as aspirin or from a loss of base due to diarrhea or laxatives.

Metabolic Alkalosis

- A rise in pH of blood and body tissues
- Can result from overuse of bicarbonates such as oral antacids or intravenous bicarbonate solutions.
- Can result from the loss of stomach acid due to chronic vomiting.

Compensated Acidosis or Alkalosis

Either:
- Kidneys compensate for pH imbalances of respiratory origin
- Respiratory system compensates for pH imbalances of metabolic origin