KAAP 310 (electrolytes and balance)

total body water (TBW)

content of average young adults is

• 60% of the body weight in men

• 50% in women

fluid compartments

areas separated by selectively permeable membranes and differing from each other in chemical composition

major fluid compartments

• 65% intracellular fluid

• 35% extracellular fluid (divided into:)

  • 25% tissue fluid

  • 8% blood plasma and lymph

  • 2% transcellular fluid

transcellular fluid

catch all category for cerebrospinal, synovial, peritoneal, pleural, and pericardial fluids; vitreous and aqueous humors of the eye; bile; and fluid in the digestive, urinary, and respiratory tracts

how is fluid exchanged

continually between compartments by way of capillary walls and plasma membranes

water movement

• water moves by:

  • osmosis from digestive tract to bloodstream

  • capillary filtration from blood to tissue fluid

  • from tissue fluid it may be:

    • reabsorbed by capillaries

    • osmotically absorbed into cells

    • taken up by lymphoid system to return to bloodstream

why do osmotic gradients between ICF ad ECF never last long

osmosis restores balance within seconds

How is direction of osmosis determined?

determined by relative concentration of solutes in each compartment

most abundant solute particles

electrolytes - especially:

• sodium salts in ECF

• potassium salts in ICF

Electrolytes

play principal role in governing body’s water distribution and total water content

fluid balance

when daily gains and losses are equal and fluids are properly distributed in the body

• typical loss and fain of ~2500 mL/day

sources of fluid gain

1. metabolic water (200mL/day) - produced as by-product of dehydration synthesis reactions and aerobic respiration

2. preformed water (700mL/day) - ingested in food and drink

routes of water loss

• urine

• cutaneous transpiration - water that diffuses through the epidermis and evaporates

• expired breath

• feces

• sweat

***listed in order of magnitude

factors affecting respiratory loss

• respiratory loss increases in cold weather

• hot, humid, weather slightly reduces respiratory loss, but increases perspiration

• prolonged heavy work can raise respiratory loss although it significantly reduces urine output

insensible water loss

output through the breath and cutaneous transpiration

sensible water loss

noticeable output, particularly through the urine and in case of sufficient sweating to produce obvious wetness of the skin

obligatory water loss

output that is relatively unavoidable

• expired air

• cutaneous transpiration

• sweat

• fecal moisture

• minimum urine output needed to prevent azotemia

**dehydrated individuals cant prevent these losses

how is the regulation of intake governed?

mainly by thirst

dehydration effects on blood

reduces blood volume and pressure while raising osmolarity

osmoreceptors

respond to angiotensin II and rising osmolarity of ECF

• signs that body has water deficit

osmoreceptors communicate with other hypothalamic neurons that produce antidiuretic hormone

• promote water conservation

• communicate with cerebral cortex to produce conscious sense of thirst

why do we salivate less when thirsty

1. osmoreceptor response leads to sympathetic output from hypothalamus that inhibits salivary glands

2. saliva is produced primarily by capillary filtration

   1. in a dehydrated person, it is opposed by the lower capillary blood pressure and higher osmolarity of the blood

what does long term satiation of thirst depend on?

absorbing water from small intestine and lowering blood osmolarity

• reduced osmolarity stops the osmoreceptor response, promotes capillary filtration, and makes saliva more abundant and watery

short term satiation of thirst

fast acting stimuli

• coolness

• moisture

• filling of stomach

prevent an animal from drinking an excessive amount of liquid (effective for 30-45 mins)

regulation of output

only significant control water output is through variations in urine volume - usually linked to adjustments in sodium reabsorption

• when sodium is reabsorbed or excreted, proportionate amounts of water accompany it

total volume of fluid remaining in body may change but osmolarity remains stable

kidney’s limitations in regulation of output

cant completely prevent water loss

cant replace lost water or electrolytes

never restore fluid volume or osmolarity

kidneys role in dehydration

support existing fluid levels and slow down the rate of loss until water and electrolytes are ingested

ADH in output regulation

provides control of water output independently of sodium

• helps kidneys retain water

• slows down decline in blood volume and rise in osmolarity

• forms a negative feedback loop

Steps of how ADH contributes to output regulation

1. increased osmolarity of blood stimulates hypothalamic osmoreceptors - stimulate posterior pituitary to release ADH

2. cells of collecting ducts of kidneys synthesize aquaporins

   1. serve as channels that allow water to diffuse out of duct into hypertonic tissue fluid of renal medulla

3. kidneys reabsorb more water and produce less urine

4. sodium continues to be excreted so the ratio of sodium to water in urine increases (urine becomes more concentrated)

how does ADH create an effective way of compensating for hypertension?

1. if blood volume and pressure are too high, or blood osmolarity is too low, ADH release is inhibited

2. causes renal tubules to reabsorb less water

3. urine output increases, and total body water declines

lack of ADH increases the ratio of water to sodium in the urine, raising the sodium concentration and osmolarity of the blood

fluid imbalance

abnormality of total volume, concentration, or distribution of water among the compartments

kinds of fluid deficiency

differ in relative loss of water and electrolytes and the resulting osmolarity of the ECF; require different strategies of fluid replacement therapy

1. volume depletion

2. dehydration

volume depletion (hypovolemia)

occurs when proportionate amounts of water and sodium are lost without replacement

• total body water declines but osmolarity remains normal

what is hypovolemia (volume depletion) caused by

• hemorrhage

• severe burns

• chronic vomiting/diarrhea

• aldosterone hyposecretion (results in inadequate sodium and water reabsorption by the kidneys)

Addison disease

aldosterone hyposecretion leading to inadequate sodium and water reabsorption by kidneys

dehydration (negative water balance)

occurs when body eliminates significantly more water than sodium

• raises ECF osmolarity

causes of dejudration

• lack of drinking water

• diabetes mellitus

• ADH hyposecretion (diabetes insipidus)

• profuse sweating

• overuse of diuretics

reasons infants are more vulnerable to dehydration

1. high metabolic rate produces toxic metabolites faster, excrete more water to eliminate them

2. kidneys aren’t fully mature and can’t concentrate urine as effectively

3. greater ratio of body surface to volume

lose twice as much water per kg of body weight by evaporation

what does dehydration affect

all fluid compartments

• as blood loses water - osmolarity rises ad water from tissue fluid enters bloodstream to balance loss

• high osmolarity of tissue fluid moves water out of cells to balance

• all 3 fluid compartments (ICF, blood, tissue fluid) lose water

most serious effect of fluid deficiency

circulatory shock due to loss of blood volume and neurological dysfunction due to dehydration of brain cells

fluid excess

less common because kidneys are very effective at compensating for excessive intake by excreting more urine

• renal failure and other causes can lead to excess fluid retention

2 types of fluid excess

1. volume excess

2. hypotonic hydration

volume excess

both sodium and water are retained and the ECF remains isotonic

• results from aldosterone hypeorsecretion or renal failure

hypotonic hydration (water intoxication/positive water balance)

more water than sodium is retained or ingested and the ECF becomes hypotonic

• can occur if you lose a large amount of water and salt through urine and you replace it by drinking plain water

  • without proportional intake of electrolytes, water dilutes ECF, and makes it hypotonic - inducing cellular swelling

how can ADH cause hypotonic hydration

hypersecretion stimulates excessive water retention as sodium continues to be excreted

fluid sequestration

condition in which excess fluid accumulates in a particular location

• total body water and osmolarity may be normal, but volume of circulating blood may drop to the point of causing circulatory shock

causes of fluid sequestration

1. edema - most common

2. hemorrhage

3. pleural effusion

electrolyte balance

state in which the amount of electrolytes absorbed by the small intestine balances the amount lost from the body (mainly through urine) and in which electrolyte concentrations in the body fluids are regulated within homeostatic limits

why are electrolytes physiologically important

• chemically reactive and participate in metabolism

• determine the electrical potential (charge difference) across cell membranes

• strongly affect osmolarity of the body fluids and body’s water content and distribution

major cations of electrolytes

1. sodium Na⁺

2. potassium K⁺

3. calcium Ca²⁺

4. magnesium Mg²⁺

5. hydrogen H⁺

major anions of the electrolytes

1. chloride Cl^-

2. bicarbonate HCO₃^-

3. phosphates P_i

what is the most accessible fluid for measurements of electrolyte concentration?

blood plasma

does electrolyte concentration affect osmolarity between the two fluid compartments

no lol they have the same osmolarity (300 mOsm/L)

Sodium functions

• principal ion responsible for resting membrane potentials of cells

  • inflow of sodium into cell is essential in depolarization driving nerve and muscle function

• principal cation of ECF

• most significant solute in determining total body water and the distribution of water among fluid compartments

• sodium gradients across membrane provide potential energy needed for cotransport of other solutes

  • Na⁺-K⁺ pump is important mechanism in creating body heat

  • sodium bicarbonate plays major role in buffering pH of ECF

Sodium homeostasis

multiple mechanisms

• tied to effects on blood pressure and osmolarity

• coordinated by aldosterone, ADH, and natriuretic peptides

Aldosterone in Sodium Homeostasis

“salt retaining hormone”

• primary role in adjustment of sodium excretion

• primary effect = urine contains less NaCl and more potassium, decreasing its pH

1. hyperkalemia directly stimulates adrenal cortex to secrete aldosterone

2. hypotension stimulates secretion through renin-angiotensin-aldosterone mechanism

where are aldosterone receptors?

cells in:

1. ascending limb of nephron loop

2. DCT

3. cortical part of the CD

Mechanism of Aldosterone’s effect in Sodium Homeostasis

1. aldosterone binds to nuclear receptors and activates transcription of a gene for the Na⁺-K⁺ pump

2. enough pumps are synthesized and installed in plasma membrane to produce a noticeable effect

3. sodium concentration in urine falls and potassium concentration rises as tubules reabsorb more sodium and secrete more hydrogen & potassium ions

4. water and Cl passively follow sodium

what does aldosterone strongly influence?

sodium reabsorption - little effect on plasma sodium concentration because it is accompanied by proportional amount of water

what inhibits renin-angiotensin-aldosterone mechanism

high blood pressure

• kidneys reabsorb almost no sodium beyond PCT

aldosterone only has small effects on:

1. urine volume

2. blood volume

3. blood pressure

increase in blood volume increases blood pressure and GFR

• even tho aldosterone increases tubular reabsorption of sodium and water, it is offset by rise in GFR with only a small drop in urine output

Antidiuretic hormone and Sodium homeostasis

modifies water excretion independently of sodium excretion - enables it to change sodium concentration

• stimulated by high concentration of sodium in blood

  • kidneys reabsorb more water, slows down further increase in blood sodium concentration

  • can’t lower concentration alone

• inhibited by drop in sodium concentration

  • more water is excreted and raises the relative amount of sodium remaining in blood

• secreted from posterior lobe of pituitary gland

natriuretic peptides and sodium homeostasis

inhibit sodium and water reabsorption and secretion of renin and ADH

• eliminate more sodium and water and lower the blood pressure

angiotensin II and sodium homeostasis

activates Na⁺-H⁺ antiport in PCT and increases sodium reabsorption, reducing urinary sodium output

sodium imbalances

• hypernatremia

• hyponatremia

hypernatremia

plasma sodium concentration excess pf 145 mEq/L

• results from administration of IV saline

• major consequences = water retention, hypertension, and edema

hyponatremia

plasma sodium concentration of less than 130 mEq/L

• usually result of excess body water instead of excess sodium secretion

• quickly corrected by excretion of excess water

Potassium functions

most abundant cation of ICF

• greatest determinant of intracellular osmolarity and cell volume

• produces resting membrane potentials and action potentials of nerve and muscle cells

• as important as sodium to Na⁺-K⁺ pump and its functions of cotransport and thermogenesis

  • essential cofactor for protein synthesis and other metabolic processes

Potassium Homeostasis

closely linked to sodium’s homeostasis (90% of K⁺ filtered by glomerulus is reabsorbed by PCT; rest excreted in urine)

• excretion controlled later in nephron by changing amount of potassium returned to tubular fluid by DCT and cortical potion of CD

what happens when potassium concentration is high

tubules secrete more potassium into filtrate and the urine may contain more potassium than glomerulus can filter from blood

what happens when blood potassium level is low

tubules secrete less

DCT and CD reabsorb potassium through intercalated cells

aldosterone and potassium homeostasis

regulates potassium balance along with sodium

• aldosterone secretion by adrenal cortex is stimulated by a rise in potassium concentration

• aldosterone stimulates renal secretion of potassium at the same time it stimulates reabsorption of sodium

  • the more sodium the less potassium

potassium imbalances

most dangerous of all electrolyte imbalances

• hyperkalemia

• hypokalemia

hyperkalemia (quick and slow rises)

(>5.5 mEq/L) can have completely opposite effect depending on whether potassium concentration rises quickly or slowly

• quick rise in extracellular potassium tends to make nerve and muscle cells abnormally excitable

• less concentration difference between ICF and ECF - outward diffusion of K⁺ is reduced

  • normally it passes into and out of cells at equal rates through Na⁺-K⁺ pump

• more K⁺ remains in cell than normal, plasma membrane has less negative resting potential and is closer to the threshold at which it will set off action potential

• slow rise in extracellular potassium concentration - nerve and muscle become less excitable

• slow depolarization of a cell inactivates voltage gated sodium channels

  • dont become excitable again until membrane repolarizes

  • inactivated sodium channels can’t produce action potentials

hypokalemia

(<3.5 mEq/L)

• ECF concentration falls, more potassium moves from ICF to ECF

• cells become hyperpolarized and nerve and muscle cells are less excitable

• occurs in people with depressed appetite - heavy sweating, chronic vomiting, diarrhea, aldosterone hyposecretion, alkalosis, laxative abuse etc

functions of calcium

• lends strength to skeleton

• activates sliding filament mechanism of muscle contraction

• serves as second messenger for some hormones and neurotransmitters

• activates exocytosis of neurotransmitters and other cellular secretions

• essential factor in blood clotting

** sustains ventricular contraction long enough to ensure effective ejection of blood

why do cells maintain low intracellular calcium concentration?

they require a high concentration of phosphate ions, and if calcium and phosphate were both concentrated inside a cell, calcium phosphate crystals would precipitate in cytoplasm

how do we avoid calcium phosphate crystals

to keep a high phosphate concentration and avoid crystallization of calcium phosphate

• cells pump out Ca²⁺and keep it at a low intracellular concentration

• also sequester Ca²⁺ in smooth ER and release it only when needed

calsequestrin

protein that binds stored Ca²⁺ and keeps it chemically unreactive

Calcium homeostasis

concentration regulated chiefly by:

• parathyroid hormone

• calcitriol (calcitonin in children)

work through effects on bone deposition and resorption, intestinal absorption of calcium, and urinary excretion

calcium imbalances

hypercalcemia

hypocalcemia

hypercalcemia

reduces sodium permeability of plasma membranes and inhibits depolarization of nerve and muscle cells

hypocalcemia

increases sodium permeability of plasma membranes, causing nervous and muscular systems to be overly excitable

Magnesium functions

second most abundant intracellular cation (after potassium)

• has wide range of effects on membrane transport, membrane electrical potentials, cell metabolism, and DNA replication

magnesium homeostasis in intestine

intestinal absorption mainly regulated by vitamin D (only 30-40% gets reabsorbed, rest passes through)

• 2/3 lost via feces, 1/3 in urine

magnesium homeostasis in nephron

retention/loss of plasma magnesium is regulated by thick segment of ascending limb of nephron loop

• smaller amounts reabsorbed in other segments of nephron

• mainly through paracellular route (driven by positive electrical potential of tubular fluid repelling the positive magnesium ions)

parathyroid hormone effect on magnesium homeostasis

governs rate of reabsorption through paracellular route, being the primary regulator of plasma Mg²⁺ level

magnesium imbalances

usually due to excessive loss from the body

hypermagensemia

hypomagnesemia

hypermagnesemia

• rare except in renal insufficiency

• sedative effect, depresses everything

  • leading to lethargy, weakness, respiratory depression/failure, hypotension, cardiac arrest

hypomagnesia

• results in hypoerirritability of nervous and muscular systems

chloride functions

most abundant anions of ECF and make a major contribution to osmolarity

• required for formation of stomach acid

• involved in chloride shift that accompanies CO₂ loading and unloading by erythrocytes

• major role in regulation of body pH

chloride homeostasis

strongly attracted to sodium, potassium, and calcium

• achieved primarily as side effect of sodium homeostasis

(when sodium is retained or excreted, chloride ions passively follow)

chloride imbalances

primary effects are disturbances in acid-base balance

hyperchloremia

hypochloremia

hyperchloremia

result of dietary excess or administration of IV saline

hypochloremia

usually side effect of hyponatremia

• sometimes results from hyperkalemia or acidosis

  • kidneys retain potassium by excreting more sodium

  • sodium takes chloride with it

phosphate functions

activate many metabolic pathways by phosphorylating enzymes and substrates

important buffers that help stabilize pH of body fluids

• relatively concentrated in ICF

• generated by hydrolysis of ATP and other phosphate compounds

• component of phospholipids, DNA, RNA, ATP, GTP, cAMP, creatine phosphate, etc

inorganic phosphates of the body fluids are an equilibrium mixture of phosphate, monohydrogen phosphate, and dihydrogen phosphate

phosphate homeostasis

usually maintained with a continual loss of excess phosphate through glomerular filtration

• readily absorbed by small intestine

  • a plasma phosphate concentration drop causes renal tubuls to reabsorbed all filtered phosphate

parathyroid hormone and phosphate homeostasis

increases excretion of phosphate as part of mechanism for increasing concentration of free calcium ions in the ECF

• lowering ECF phosphate concentration minimizes formation of calcium phosphate and helps support plasma calcium concentration

• phosphate excretion rates strongly affected by pH of urine

phosphate imbalances

not as critical as other electrolytes

• body can tolerate broad variations with little immediate effect on physiology