fluids, electrolytes, and acid base balance

•Body Water Content

•Human body is between 45% and 75% fluid

•Depends on age and amount of adipose tissue/muscle tissue

•Infants are 73% or more water (low body fat, low bone mass)

•Adult males: ~60% water

•Adult females: ~50% water (higher fat content, less skeletal muscle mass)

•Adipose tissue is least hydrated of all

•Total body water in adults averages ~40 L

•Water content declines to ~45% in old age

Ratio of adipose to skeletal muscle tissue

•Adipose tissue is about 20% water

•Skeletal muscle is about 75% water

•Males have more skeletal muscle, so slightly higher %

•% decreases with increased body fat

•Determines susceptibility to fluid imbalance

•Individuals with lower percentage, at higher risk

•for example, elderly at more risk than young adults

•Two main fluid compartments

Intracellular fluid (ICF) and extracellular fluid (ECF).

Intracellular fluid (ICF) compartment

•fluid inside cells accounts for 2/3 of total body fluid

Extracellular fluid (ECF) compartment

•fluid in two main ECF compartments outside cells accounts for one-third of total body fluid:

Plasma

•3 L (fluid in blood vessels)

Interstitial fluid (IF):

•12 L in spaces between cells

•Also considered part of IF: lymph, CSF, humors of the eye, synovial fluid, serous fluid, and gastrointestinal secretions

ECF: Two components of extracellular fluid

interstitial fluid and blood plasma

•Similar to each other except in one regard—protein is present in blood plasma, but very little in interstitial fluid

•Both high in Na+, Ca2+, Cl−, HCO3−

ICF

contains more soluble proteins than plasma

high concentrations of potassium, magnesium, phosphate (PO43-), sulfate ions (SO42-), negatively charged proteins

Osmotic and hydrostatic pressures regulate continuous exchange and mixing of fluids

Water moves freely along osmotic gradients

Water moves from LOW osmotic pressure (dilute) to HIGH osmotic pressure (concentrated) - from hypotonic solution

All body fluid osmolality is almost always equal

Change in solute concentration of any compartment leads to net water flow

↑ECF osmolality → water leaves cell

↓ ECF osmolality → water enters cell

When you drink water - goes into the blood from digestive system to interstitial fluid to cells, reverse if don't drink.

Exchanges between plasma and IF occur across capillary walls:

•Fluid leaks from arteriolar end of capillary, reabsorbed at venule end

•Lymphatics pick up remaining fluid and return it to blood

Exchanges between IF and ICF occur across cell membrane

•Two-way osmotic flow of water

•Ions move selectively into or out of cell

•Nutrients, wastes, gases have unidirectional flow

Fluid intake equal to fluid output

2500 ml/day

Ingested (preformed) water

ingested foods and beverages ~2300ml

Metabolic water

•small amount from metabolism (produced by cell respiration) ~200ml

Loss of water from body:

urine (60%), insensible water loss (lost through skin and lungs), perspiration, and feces

•Osmolality is maintained around 280-300 mOsm

•Rise in osmolality

•Stimulates thirst

•Causes ADH release

•Decrease in osmolality

•Causes inhibition

Causes ADH inhibition

Water loss can be described as

Sensible and insensible/Obligatory and facultative

sensible water loss

Measurable, Includes fluid lost through feces and urine

insensible water loss

- Not measurable, Fluid lost in expired air, Fluid lost from skin through sweat and cutaneous transpiration

Obligatory water loss

•Loss of water that always occurs, Water lost through breathing and through the skin, Water lost through feces and minimal urine needed to eliminate waste

Facultative water loss

•Controlled water loss, Dependent on hydration of body, Hormonally regulated in kidney nephrons:

•Only mechanism to control fluid output

•Can decrease fluid loss if body is dehydrated

Fluid Imbalance

occurs if fluid output does not equal fluid intake

fluid imbalance 5 categories

•Volume depletion, volume excess, dehydration, hypotonic hydration, and fluid sequestration

•First four of these can be differentiated by two criteria:

•Does the fluid imbalance change the osmolarity of body fluid?

•Is the fluid imbalance caused by excess of deficiency of body fluid?

Fluid imbalance with constant osmolarity

Occurs when isotonic fluid is lost or gained

1.Volume depletion

•Occurs when isotonic fluid loss is greater than isotonic fluid gain

•For example, hemorrhage, severe burns, chronic vomiting, diarrhea, hyposecretion of aldosterone

2.Volume excess

•Isotonic fluid gain is greater than isotonic fluid loss

•Fluid intake normal but decreased fluid loss through kidneys

•In both, no change in osmolarity

•No net movement of water between compartments

3. Dehydration

- ECF water loss due to - hemorrhage, severe burns, prolonged vomiting or diarrhea, profuse sweating, water deprivation, diuretic abuse, endocrine disturbances, diabetes

•Blood plasma becomes hypertonic, Water shifts from cells into interstitial fluid and blood plasma Possible dehydration of body cells - May lead to mental confusion, hypovolemic shock, and loss of electrolytes

4. Hypotonic hydration - Cellular overhydration, or water intoxication

•Occurs with renal insufficiency or rapid excess water ingestion

•ECF osmolality decreases, causing hyponatremia

•Results in net osmosis of water into tissue cells and swelling of cells

•Symptoms: severe metabolic disturbances, nausea, vomiting, muscular cramping, cerebral edema, and possible death

•Treated with hypertonic saline

5. Fluid sequestration

Total body fluid is normal, but distributed abnormally

•Example- Edema

•Atypical accumulation of IF, resulting in tissue swelling (not cell swelling)

•Only volume of IF is increased, not of other compartments

•Can impair tissue function by increasing distance for diffusion of oxygen and nutrients from blood into cells

Edema causes

Could be caused by increased fluid flow out of blood or decreased return of fluid to blood

1.Increased capillary hydrostatic pressure

2.Inflammation

3.Decreased lymphatic return

4.Low capillary osmotic pressure

means of regulating fluid balance

•Monitor blood volume

•Blood pressure

•Blood plasma osmolarity

•Relationships between these variables:

Fluid intake is less than output

•Decreases blood pressure and blood volume

•Increases blood osmolarity if more water is lost than solutes

Fluid intake is greater than output

•Increases blood pressure and blood volume

Decreases blood osmolarity if water gain exceeds solute gain

Regulating fluid intake

•Thirst mechanism is driving force for water intake - regulated by hypothalamic thirst center.

•Intake regulated by various stimuli that activate/inhibit the thirst center

Stimuli that activate the thirst center

-decreased blood volume and blood pressure

-increased blood osmolarity

-decreased salivary secretions

•Decreased blood volume and blood pressure

•Renin released from kidney, production of angiotensin II which stimulates thirst center

•Increased blood osmolarity

•Due to insufficient water intake

•Stimulates sensory receptors in thirst center directly

•Stimulates hypothalamus to trigger release of ADH

Decreased salivary secretions

•Sensory input relayed from receptors in mucous membranes

Stimuli that inhibit the thirst center - Fluid intake is greater than fluid output

•Increased blood volume and blood pressure

•Inhibits kidney from releasing renin, Decrease in angiotensin II results in reduced stimulation of thirst center

•Decreased blood osmolarity

•Thirst center is no longer stimulated directly, Decreased stimulation of ADH release

•Increased salivary secretions

•Decreased sensory input to thirst center

•Distension of stomach

•Stretch caused by fluid entering

Inhibitory sensory impulses relayed to thirst center

Regulating fluid output

•Regulated through kidneys by controlling urine output

•Four hormones involved in regulating urine output

•Angiotensin II, antidiuretic hormone (ADH), and aldosterone

•Decrease urine output to increase blood volume and pressure

•Atrial natriuretic peptide (ANP)

•Increases urine output to decrease blood volume and pressure

Influence of Antidiuretic Hormone (ADH)

•Water reabsorption in collecting ducts is proportional to ADH release

•Decreased ADH leads to dilute urine (increased urine output) and drop in volume of body fluids (decreased blood volume, decreased BP)

•Increased ADH leads to concentrated urine (decreased urine output), due to reabsorption of water, causing increased volume of body fluids (increased blood volume, increased BP)

•Hypothalamic osmoreceptors sense ECF solute concentration and regulate ADH accordingly

•Other factors may trigger ADH release

•"Large" changes in blood volume or pressure

•Decreased BP causes increased ADH release due to blood vessel baroreceptors and renin-angiotensin-aldosterone mechanism

•Decreased BP/volume can be caused by:

•Intense sweating, vomiting, or diarrhea, severe blood loss, traumatic burns, and prolonged fever

Water is the

•universal solvent

•Solutes are substances dissolved in water

•Solutes are classified as nonelectrolytes and electrolytes

•Electrolytes and nonelectrolytes

•Nonelectrolytes: most are organic molecules

•Do not dissociate in water

•Examples: glucose, lipids, creatinine, and urea

•No charged particles are created

•Electrolytes

•Dissociate into ions in water

•Examples: inorganic salts, all acids and bases, some proteins

•Ions conduct electrical current

•Greater osmotic power than nonelectrolytes

Electrolyte Balance

•Electrolyte balance usually refers only to salt balance even though electrolytes also include acids, bases, and some proteins

•Salts control fluid movements, provide minerals for excitability, secretory activity, and membrane permeability

•Salts enter body by ingestion and metabolism and are lost via perspiration, feces, urine, vomit

Na+ - Most abundant

•cation in ECF (99% in ECF and 1% in ICF)

•Gradient maintained by Na+/K+ pumps

Sodium

Most important electrolyte in determining blood plasma osmolarity and regulating fluid balance

•Only cation exerting significant osmotic pressure

•Controls ECF volume and water distribution because water follows salt

•Changes in Na+ levels affects plasma volume, blood pressure, and ECF and IF volumes

•Changes in plasma volume

•Retention of Na+ and water causes increase in blood volume and blood pressure

•Loss of Na+ and water with opposite effects

•Individuals with high blood pressure are put on low-salt diet

Major Electrolytes: Location, Functions, and Regulation Sodium

•Concentration of Na+ also influences excitability of neurons and muscles

•Renal acid-base control mechanisms are coupled to sodium ion transport

•Amount lost in urine regulated by aldosterone, ADH, and ANP

Sodium-2

There are no known receptors that monitor Na+ levels in body fluids

•Na+-water balance is linked to blood pressure and blood volume control mechanisms

•Changes in blood pressure or volume trigger neural and hormonal controls to regulate Na+ content

in general

•65% of Na+ is reabsorbed in proximal tubules, and 25% is reclaimed in nephron loops

•Na+ is never secreted into filtrate

Major hormones involved in sodium regulation = aldosterone, angiotensin II, ANP, female sex hormones

•Sodium imbalance

•Most common type of electrolyte imbalance

•Above normal level, hypernatremia

•Below normal level, hyponatremia

•Most changes resulting from changes in water content

Influence of aldosterone and angiotensin II

•Aldosterone has largest role in Na+ regulation by kidneys

•When aldosterone concentrations are high:

•Na+ is actively reabsorbed in DCT and CT and water follows, so ECF volume increases = decreased urine output, increased blood volume = increased blood pressure

•When aldosterone concentrations are low:

•Na+ is not actively reabsorbed and is lost to urine, along with increased loss of water, so decreased water reabsorption = increased urine output, decreased blood volume = decreased blood pressure

Renin-angiotensin-aldosterone mechanism is main trigger for aldosterone release:

•Granular cells of JGA secrete renin in response to:

•Sympathetic nervous system stimulation

•Decreased filtrate NaCl concentration

•Decreased stretch of granular cells, due to decreased blood pressure

•Renin à angiotensin II à aldosterone

•Aldosterone also triggered by ↑ K+ levels in ECF

•Aldosterone brings about its effects slowly (hours to days)

Influence of atrial natriuretic peptide (ANP)

•Released by atrial cells in response to stretch caused by increased blood pressure

•Decreases blood pressure and blood volume by:

•Inhibiting ADH, renin, and aldosterone production

•Increasing excretion of Na+ and water

•Promoting vasodilation directly and by decreasing production of angiotensin II

Influence of female sex hormones

•Estrogens: increase NaCl reabsorption (like aldosterone)

•Leads to H2O retention during menstrual cycles and pregnancy

•Progesterone: decreases Na+ reabsorption (blocks aldosterone)

•Promotes Na+ and H2O loss

Influence of cardiovascular baroreceptors

•Baroreceptors alert brain to increases in blood volume and pressure

•Sympathetic nervous system impulses to kidneys decline, causing:

•Afferent arterioles to dilate

•GFR increases

•Increased Na+ and water output

Reduced blood volume and pressure

Importance of potassium

•98% in ICF, 2% in ECF

•Maintained by Na+/K+ pump

•Affects resting membrane potential (RMP) in neurons and muscle cells (especially cardiac muscle)

•Increases in ECF [K+] (hyperkalemia) cause decreased RMP, causing depolarization, followed by reduced excitability

•Decreases in ECF [K+] (hypokalemia) cause hyperpolarization and nonresponsiveness

•Most lethal of electrolyte imbalances

•Cardiac or respiratory arrest

•Disruption in [K+] (hyper- or hypokalemia) in heart can interfere with electrical conduction, leading to sudden death

Regulation of Potassium Balance

•K+ is also part of body's buffer system

•H+ shifts in and out of cells in opposite direction of K+ to maintain cation balance, so:

•With increase in plasma K+ (hyperkalemia), K+ moves from ECF into ICF

•Hyperkalemia - acidosis (↑K+ -- ↑ H+/↓ pH)

•With decrease in plasma K+ (hypokalemia), K+ moves from ICF to ECF

•Hypokalemia - alkalosis (↓K+ -- ↓H+/↑ pH)

•Imbalances interfere with activity of excitable cells

•Certain hormones (for example, insulin) can induce shifts

Regulation of Potassium Balance 2

•Kidneys have limited ability to retain K+, so most K+ is lost in urine; may lead to deficiency if not replaced in diet

•Greater amounts are lost if plasma K+ high, increased aldosterone secretion, and high blood pH

•K+ balance is controlled in DCT and collecting ducts by regulating amount secreted into filtrate

•Most important factor affecting K+ secretion is its concentration in ECF

•Aldosterone stimulates K+ secretion (and Na+ reabsorption)

Chloride Ion (Cl-)

•Associated with Na+

•Follows Na+ by electrostatic interactions

•Amount lost in urine dependent upon blood plasma Na+

•Regulated by same mechanisms

•Most abundant anion in ECF

•Obtained in diet, lost in sweat, stomach secretions, and urine

•Increased blood chloride levels: hyperchloremia

•Decreased blood chloride levels: hypochloremia

•Calcium ion (Ca2+)

•Most abundant electrolyte in bone and teeth

•Needed for muscle contraction and neurotransmitter release

•Serves as a second messenger and participates in blood clotting

•Ca2+ in ECF is important for:

•Blood clotting

•Cell membrane permeability

•Secretory activities

•Neuromuscular excitability: most important

Hypocalcemia

increases neuromuscular excitability and can lead to muscle tetany

hypercalcemia

inhibits neurons and muscle cells and may cause heart arrhythmias

•Regulation of calcium and phosphate

•99% of body's calcium is found in bones as calcium phosphate salts

•Calcium balance controlled by parathyroid hormone (PTH) - rarely deviates

•PTH promotes increase in calcium levels by targeting

•Bones—osteoclasts break down matrix, releasing calcium and phosphate to blood

•Kidneys—increases calcium reabsorption; decreases phosphate ion reabsorption

•Small intestine—increases calcium absorption (indirectly through stimulation of kidney to activate vitamin D precursor)

•98% of filtered calcium reabsorbed is due to PTH

•If ECF calcium levels are normal, PTH secretion is inhibited

•75% of filtered phosphates are reabsorbed in PCT

Phosphate ion (PO4)3-

•Most abundant anion in ICF

•85% stored in bone and teeth as calcium phosphate

•Component of DNA, RNA, and phospholipids

•Intracellular buffer and urine buffer

Magnesium ion (Mg2+)

•Primarily within bone or within cells

•Second most abundant cation in ICF

•Participates in hundreds of enzymatic reactions

•Assists in Na+/K+ pump

•Important in muscle relaxation

•Lost from body in sweat and urine

•Regulated through the kidney

Renin

•released from the JG apparatus

•In response to low blood pressure or sympathetic stimulation

•Renin and ACE cause formation of angiotensin II

•Actions of angiotensin II

•Targets Blood vessels

•Stimulates vasoconstriction to increase peripheral resistance

•Increases blood pressure

Kidneys -

•- Decreases urine output, Helps maintain blood volume, blood pressure

Thirst center

•- Stimulates center in hypothalamus, With increased fluid intake, increased blood volume and pressure

Hypothalamus and adrenal cortex-

•Stimulates both to activate posterior pituitary to release ADH, Stimulates adrenal cortex to release aldosterone

Acid-Base Balance

•pH affects all functional proteins and biochemical reactions, so it is closely regulated by the body

•Normal pH of arterial blood: pH 7.4 (7.35 - 7.45)

•Alkalosis or alkalemia: arterial pH >7.4

•Compensated = pH 7.4-7.45

•Uncompensated = pH >7.45

•Death = pH > 7.8

•Acidosis or acidemia: arterial pH

•Compensated = pH 7.35-7.4

•Uncompensated = pH

H+ concentration altered by:

•Input of both acid and base

•Output of both acid and base (by kidney)

•Respiratory rate

•Chemical buffers

•pH inversely related to H+ concentration

•Adding an acid increases H+, base reduces it

•Two categories of acids in body—fixed and volatile

•Fixed acid

•Nonvolatile acid, metabolic acid

•Wastes produced from metabolic processes

•Regulated by the kidney

volatile acid

•Carbonic acid produced when carbon dioxide combines with water

•Occurs readily with the enzyme carbonic anhydrase

•CO2 + H2O

•Referred to as volatile because it is produced from an expired or "evaporated" gas

•Regulated by respiratory system

•Major inputs of acid into the blood come from

•Nutrients absorbed from the GI tract

•More acid from GI tract due to diet high in animal protein and wheat (in U.S.)

•Nutrients from body cells

•Waste products from metabolic processes

•For example, lactic acid, phosphoric acid, ketoacids

•Consequence of diarrhea

•Kidney response to maintain normal pH

•Reabsorbs all filtered HCO3− along nephron

•Synthesizes and absorbs new HCO3−

•Excretes H+ into filtrate

Conditions causing blood H+ concentration to decrease

•Rare

•For example, antacid ingestion

•For example, vomiting with loss of HCl

•Response by renal tubules

•Do not reabsorb all filtered HCO3− along the length of the nephron tubule

•Secrete HCO3− from blood into filtrate

•Reabsorb H+ in exchange

•Kidneys act as physiologic buffering system

•Eliminate excess acid or base

•Takes several hours to days

•Most powerful method to maintain blood H+

•When the body is at rest:

•CO2 normally eliminated from lungs at same rate produced

During exercise

•CO2, H+, and O2 levels detected by chemoreceptors

•Relayed to respiration center to alter breathing rate

•Changes in CO2—most important variable

•Carbonic acid levels dependent on CO2 levels

•CO2 and H2CO3 do not usually have daily fluctuations and do not normally affect acid-base balance

Concentration of hydrogen ions is regulated sequentially by three mechanisms:

• Chemical buffer systems

•Rapid, first line of defense

• Brain stem respiratory centers

•Acts within 1-3 minutes

• Renal mechanisms

•Most potent, but require hours to days to effect pH changes

Chemical buffer

•system of one or more compounds that act to resist pH changes when strong acid or base is added

•Will bind H+ if pH drops or release H+ if pH rises

•Act in minutes to temporarily prevent pH changes

•Composed of one or two types of molecules

•Can bind and release H+ within a fraction of a second

•Temporary and limited, until physiologic buffering systems can eliminate the excess acid or base

•Three major buffering systems:

•Bicarbonate buffer system

•Phosphate buffer system

Protein buffer system

Bicarbonate buffer system

•Buffers both ICF and ECF but is Most important buffering system in ECF

•If strong acid is added (= ↑ H+), HCO3- binds H+ and forms H2CO3

•bicarbonate ion converts a strong acid to a weak acid

•pH decreases only slightly, unless all available HCO3- (alkaline reserve) is used up

•[HCO3-] is closely regulated by kidneys

Bicarbonate buffer system 2

•If strong base added, it causes H2CO3 to dissociate and donate H+

•carbonic acid converts a strong base to a weak base

•pH rises only slightly

•H2CO3 supply is almost limitless (from CO2 released by respiration) and subject to respiratory controls

Phosphate Buffer System

•Action nearly identical to bicarbonate buffer

•Components are sodium salts of:

•Dihydrogen phosphate (H2PO4-), a weak acid

•Monohydrogen phosphate (HPO42-), a weak base

•Not important for buffering plasma; effective buffer in urine and ICF, where phosphate levels are high

H+ + HPO4-2 « H2PO4-

•monohydrogen phosphate ion converts a strong acid to a weak acid

•dihydrogen phosphate ion converts a strong base to a weak base

protein buffer system

•Intracellular proteins are most plentiful and powerful buffers; plasma proteins also important

•Protein molecules are amphoteric (can function as both weak acid and weak base)

Protein Buffer system 2

•When pH rises, organic acid or carboxyl (COOH) groups can release H+

•When pH falls, NH2 groups can bind H+

•Hemoglobin functions as intracellular buffer

•Conditions caused by acid-base disturbance

•Acidosis: arterial blood pH below 7.35

•Alkalosis: arterial blood pH above 7.45

•Acid-base disturbance

•Occurs when buffering capacity is exceeded

•Transient change in H+, resulting in a change in pH beyond normal range

•Types of disturbances classified by

•Whether the primary disturbance is respiratory or metabolic

•Whether the pH change is acidic or alkaline