Body Content:

Singly the largest constituent in the body

Infants (73%), Adult Males (60%), Adult Females (50%), Old Age (45%)
Water amounts vary from person to person:
Increase muscle -> Increase Water
Increase Fat -> Decrease Water (fat is least hydrated)

Location:

Two Fluid Compartments = 40L

Intracellular Volume (ICF) = (2/3) 25L, 40% body weight
Extracellular Volume (ECF) = (1/3) 15L, 20% body weight
o Subdivided into two subcompartments:
Interstitial Fluid: 80% of ECF= 10-12L
Fluids surrounding the cells and between tissue cells
Including transcellular: Lymph, cerebrospinal fluid, humors of
the eye, synovial fluid, serous fluid, secretions of the
gastrointestinal tract
Plasma (intravascular): 20% of ECF = 3-5 L
Fluid within blood vessels

Composition of Body Fluids:

Water is a universal solvent

Solutes: electrolytes and nonelectrolytes
Electrolytes:
Chemical compounds that dissociate into ions
Have ionic bonds that dissolve in body fluids and the ions become either anions (-) or
cations (+)
Ex: acid, bases, salts and some proteins
when they are dissolved they contribute to two or more solute particles
contribute to a greater osmotic power activity than nonelectrolytes
Nonelectrolytes:
Have covalent bonds, that prevent them from dissociating in solution
As a result they have no charge
Mostly organic molecules such as glucose, lipids, creatinine and urea

Comparison of Solutes: (plasma and interstitial fluid are very similar)

Extracellular fluid:
Main electrolytes: Na+, Cl-, Ca++, HCO3 Plasma contains many more protein anions and Na+ ions than interstitial fluid
Interstitial fluid contains more Cl- ions than plasma does

There are more proteins in intracellular than extracellular fluid

Intracellular fluid:
Main electrolytes: K+, HPO4-, Ma++

Fluid Movement among Compartments:

Continuous exchange and mixing of body fluids are regulated by osmotic and hydrostatic
pressure
Water moves freely between compartments along osmotic gradients
Solutes are unequally distributed because of their size, electrical charge so any change
in solute concentration in any compartment leads to net water flows
ECF solute concentration is the major regulating factor in both ECF and ICF
Between plasma and interstitial fluid: (solutes move in both directions)
Capillary dynamics: (movements depends on 4 pressures)
o Capillary hydrostatic pressure (solutes forced out of blood into interstitial
space)
o Capillary osmotic pressure (solutes suck water into blood from interstitial fluid)
o Interstitial fluid hydrostatic pressure (into blood from interstitial fluid)
o Interstitial fluid osmotic pressure ( into interstitial fluid from blood)
Kidney Filtration: (movement depends on 3 pressures)
Glomerular hydrostatic pressure
Glomerular osmotic pressure
Capsular hydrostatic pressure
Between interstitial fluid and intracellular fluid: (more complex)
Usually unidirectional for ions
o Movement of nutrients (glucose) and respiratory gases (O2 in CO2 out)
Water has a two-way osmotic flow
o This movement is mostly dependent on the movement of Na+ (outside the cell)
and K+ (in the cell),
o Also depended on secretion of aldosterone and ADH
o Decreased Na+ concentration in interstitial fluid (decrease interstitial fluid
osmotic pressure) -> water leaves and enter cell -> water intoxication and/or
vice versa

Water Balance:

Intake: due to the thirst mechanism: stimuli

o A decrease in plasma fluid volume > 10% or an increase in osmolality by 1% to2% leads
to decrease fluid into interstitium and cells in the plasma -> decreased saliva -> dry
mouth and throat or stimulation of osmoreceptors and crenation of cells in the
hypothalamus -> thirst

Wetting of mucosa of mouth and throat (drinking fluids) will start quenching of thirst
almost immediately, but major quenching of thirst and inhibition comes with distension
of intestine, H2O absorption, and decreased osmolarity of the hypothalamus.

Output:
Insensible water loss: vaporizes out of the lungs, or diffuses through skin
Sensible water loss: feces 4%, urine 60%, seating 8%
Urine production is regularly 1500ml, but may decrease to 500ml to conserve fluids
Increase loss of fluids can be due to vomiting, diarrhea, extensive skin burns, increase
blood pressure, or even changes in diet

Disorders:

Dehydration:
Water output exceeds intake Negative water balance
Loss of H2O from cell to interstitium to plasma
Increased osmolality
Causes:
o Increased H2O loss (increased sweating, vomiting, diarrhea, hemorrhaging,
severe burns and diuretic abuse
o Increased osmolality
o S/S: decrease urine production (oliguria), dry mouth, thrist, and dry flushed skin
o TX: salt pills
Hypotonic hydration: dilutional hyponatremia or water intoxication
Decreased osmolality
Seen with low Na+ levels in ECF either by not enough Na+ being reabsorbed or Na+ ratio
is relatively low due to excess water -> increased fluid into cells
S/S: muscle weakness, headaches, hypotension, tachycardia, and circulatory shock.
Severe case-> mental confusion, stupor and coma
Tx: intravenous, hypertonic infusion
Edema:
Atypical accumulation of fluid in the interstitial space, leading to tissue (but not cell)
swelling
There needs to be a 30% increase in interstitial fluid, before edema will be detected
S/S:
o Increased fluid in the interstitial spaces (swelling)
o Increased may impair tissue function due to increased distance between
capillaries and cells (O2 and nutrients cant reach cells)
Causes of edema: (many factors can contribute to edema)
o Any event that enhances movement of fluids out of the blood vessels into the
tissues (capillary hydrostatic pressure), or retards movement, and causes backup of blood into the capillaries (osmotic pressure)

o
o

o
o

Increase of capillary permeability as in certain allergic response (inflammatory

response)
Elevated intra-capillary pressure (hydrostatic pressure)
Increased arterial dilation
Blockage of veins
Increased venous pressure and/or increased flow to capillaries
Pressure -> increased filtration rate (more fluid into interstitium)
Increased interstitial fluid colloid osmotic pressure due to blocked lymphatic:
Increased protein in interstitial space/ decreased in plasma
Increased proteins spilling into interstitium (result of trauma or blister),
decrease in the plasma
Decrease plasma colloid osmotic pressure (in capillary) due to loss of excess
protein in urine (kidney disease)
With long-term edema there may be decreased blood volume leading to a
decreased blood pressure

Electrolyte Balance: electrolytes: salts, acids, and bases (mostly salts)

At least three functions:

1) Provides essential minerals
2) Controls osmotic fluid movement between compartments
3) Help maintain acid-base balance (essential for cellular function)
Sodium: has a role both in fluid and electrolyte balance
Most abundant ECF ion (95% of all solutes)
Essential for impulse transmission of both muscle and nerves (with K+)
The key cation in fluid electrolyte balance (changes in Na+ levels of plasma [fluid
volume] affect all three compartments)
Helps maintain acid-bace balance by exchanging with H+
Plasma Na+ levels contribute to osmolality (contribute to fluid shift)
Regulation of sodium balance:
o Aldosterone: by obligatory reabsorption of Na+ (seen with high BP)
o Atrial natriuretic peptide regulation:
Atrial cells sense an increase BP (increase blood volume), it will release
ANP
ANP to the kidneys -> where it causes increased sodium (H2O) excretion
Inhibits the release of ADH, aldosterone, angiotensin, and retin
Decreases BP
o ADH regulation (its relationship to Na+)
Hypotonic solution-> decreased Na+ concentration(high fluid volume) ->
decreased ADH -> increased dilute urine production and output, vice
versa

ADH will determine, at the site of the DCT and the collecting ducts,
whether the urine will be dilute or concentrated
o Baroreceptors (cardiovascular system)
Increased BP (increased BV): baroreceptors (in heart, aorta, carotid
arteries) send messages to hypothalamus -> to decreased sympathetic
input to kidneys -> dilation of afferent arteriole -> increased filtration
rate -> increased Na+ and water loss (pressure diuresis), vice versa
o Values:
Normal: 135-145 mEq/L
Abnormal: hyponatremia < 135 mEq/L -> (due to an) incr. H2O intake,
Incr. ADH

Hypernatremia > 145 mEq/L -> (due to an) diabetes insipidus

Potassium: has a role, both in fluid and electrolyte balance
Primary intracellular cation
Helps maintain fluid volume in cells and controls pH
Shifts in opposite direction to Na+ and H+ ions; helps maintain electrolyte balance
Incr. K+ in ECF (interstitium) with acidosis (Incr. H+ ions in the cell), and Decreased K+
with alkalosis (K+ moves into cell)
Essential for impulse transmission of muscles and nerves (with Na+)
Helps maintain membrane potential and cell excitability
Regulation of potassium balance:
o Aldosterone: enhances secretion of K+
o Increase of K+ (decr. Na+) in interstitium, around adrenal cortex will stimulate
release of aldosterone which will cause K+ secretion/excretion
o Tubule cell regulation: increase potassium itself will cause an increase in tubule
cell secretion of potassium and lost in urine
Values:
o Normal: 3-5 mEq/L
o Abnormal: hypokalemia < 3 mEq/L -> diarrhea
o
Hyperkalemia > 5 mEq/L -> burns & renal failure
Calcium:
Calcium in ECF is need for:
o Normal blood clotting
o Cell membrane permeability
o Chemical transmitter release at axon terminals (neuromuscular excitability)
o Helps form bones and teeth (99% of calcium is found in bone and teeth)
Calcium in ICF is need for: muscle contraction and nerve contraction
PTH functions to increase levels of calcium in blood
o Bones: activates bone-digesting osteoclasts, which break down bone matrix,
resulting in the release of Ca++ and HPO4-- (calcium phosphate) to the blood.

Small Intestine: enhances intestinal absorption of Ca++ indirectly by stimulating

kidneys to transform vitamin D to its active form (through calcitrol), which is
necessary for calcium absorption by small intestines.
o Kidneys: Increases calcium reabsorption by the renal tubules while decreasing
phosphate ion reabsorption (Incr. absorption, Decr. Excretion of calcium)
Antagonist to calcitonin (CT)
It uses a negative feedback system:
o Humoral control: it has a direct effect on the parathyroid gland (it bypasses
pituitary gland)
o Increase blood calcium levels cause PTH secretion to stop.
Values:
o Normal: 9.8-10.1 mg/dL
o Abnormal: hypocalcemia < 8.9 mEq/L -> acute pancreatitis
o
Hypercalcemia > 10.1 mEq/L -> hyperparathyroidism
Magnesium:
Has a role, structure and function of:
o Primarily in ICF electrolyte
o 50% in skeleton, the rest in cells
o Needed for metabolism of protein synthesis (and other carbs)
o Neuromuscular function:
A decrease Of Mg++ will lead to:
Increased irritability (tetany-> convolutions) and
hyperexcitability of CNS
An Increase of M++ will lead to:
Depression of CNS which may lead to coma
o May cause arrhythmia in the heart
o Regulation of magnesium Balance:
Increase excretion due to Increased Ca++, increased Mg++, Increased
ECF volume, decreased parathyroid hormone
o Values:
Normal: 1.5-2.5 mEq/L
Abnormal: hypomagnesaemia < 1.5 mEq/L -> malnutrition

Hypermagnesaemia > 2.5 mEq/L -> renal failure

Acid-Base Balance:
A. pH balance
1. Normal pH: 7.35-7.45 (arterial blood= 7.4, venous blood and interstitial fluid=7.35,
intracellular fluid=7.0)
Lower pH in ICF and venous blood due to acidic metabolites and CO2, H+, and lactic acid
Most H+ ions are produced by, or are, end products of metabolism
2. H+ concentration is regulated by:

 Chemical buffers: acts in mseconds, firs-line defense (binds H+ ions, removing them
from solution, not the body)exists in plasma in a 1H+ to 20 HCO3 ratio
Respiratory center (brain stem): acts in minutes (1-3); adjusts breathing rate
Renal mechanism: acts in hours to stop; most potent and longest lasting (reninangiotensin mechanism)
B. Chemical Buffers:
1. Acids are proton donors: Acids liberate H+ and bases accept them
2. To buffer (add acids or bases), buffers help prevent extreme changes in pH
3. Buffer can chemically combine with hydrogen ions (H+) as their concentration increases and
to release them (H+) as their concentration starts to fall
4. Because the concentration of free H+ determines the acidity of a solution, we have in place
3 buffer systems:
Bicarbonate buffer system:

Buffers ECF: interstitial fluid and blood plasma

Uses a series of simple chemical reactions (coupled reactions)
At a normal pH (7.4) the bicarbonate ions outnumber hydrogen ions (H+) 20-1
Bicarbonate ions (HCO3) are needed more than carbonic acid due to the normal ongoing
acidification due to metabolism (carbonic acid comes from cellular respiration; CO2 released)

Phosphate buffer system:

Phosphate buffers (NaH2PO4 [weak acid] and NaHPO4 [weak base])

More useful in buffering urine and ICF than plasma and interstitial fluid

Protein buffer system:

Most abundant in body cells and plasma

Proteins are composed of amino acids
Amino acids are amphoteric molecules: they can act either as base or an acid depending on the
pH of its environment
They contain:
Carboxyle groups COO-H+ (acts like an acid) & gives off H+ ions (proton)
Amine groups NH2 (that act as a base) & accept an H+ (or two)

Respiratory System Regulation of H+ Ion Concentration:

1. CO2 (+) H20 (-><-) H2CO3 (-><-) H+ (+) HC03
Breathing faster (hyperventilation) will decrease the CO2 (Increase CO2 exhale) in the
body fluids, and the pH will increase (alkalosis) -> pushes the reaction to the left
Breathing slower will increase the CO2 (decrease CO2 exhaled) in the body fluids and
the pH will decrease (acidosis) -> pushes the reaction to the right

 Respiratory center in medulla will sense changes and can cause expulsion of CO2 as
quickly as it is formed in the body (tissues)
2. pH changes of 0.2 up or down can be achieved by doubling of halving breathing rate (alveolar
ventilation), respectively
Respiratory system abnormalities:
pCO2 is the primary indicator of respiratory function to maintain pH:
1. Respiratory Acidosis:
Develops slowly over a period of time and it usually results from:
o Head or chest trauma and respiratory diseases
Respiratory acidosis is usually treated with bronchodilators and small amounts of
oxygen to increase air exchange in the lungs
Asphyxia: anything that interferes with breathing (specifically the elimination of CO2),
causing accumulation of CO2 in blood
In cases of pathology (emphysema [the lungs cannot perform normally due to an
increase of dead air space], pneumonia, pulmonary edema, injury to the respiratory
center in the medulla), in all cases the lungs do not expel enough CO2
2. Respiratory alkalosis:
Usually results from:
o The body being stressed: as with shock, sepsis, trauma, and asthma
o High altitudes or sever anxiety, any alteration in breathing that may be a result
of O2 deficiency that will make one breath faster for O2 therefore expelling
more CO2
o Hyperventilation, which eliminates an excessive amount of CO2, too much acid
is blown off from increased respirations or hyperventilation
The increase in alkalosis causes the tingly sensation around the mouth and in fingertips. Because
of hyperventilation, blood is slowed to the brain so the respiratory center tells the body to
increase respirations. In psychogenic hyperventilation, the symptoms of tingling and feeling of
smothering continue to worse

3. Metabolic acidosis:
Usually results from:
o Due to abnormal increased acid metabolites EXCEPT those caused by too much
or too little carbon dioxide in the blood
o Caused by: severe diarrhea, renal disease, untreated diabetes mellitus,
starvation
o Loss of bicarbonates
Decrease of bicarbonate ions (HCO3-) may result from: excessive
diarrhea and renal tubular dysfunction
o Increased acid production due to serious illness or injuries, and decreased
blood flow
Drug intoxication or abuse, or sever illness.

Increase alcohol, increase lactic acid, increase ketones (due to diets,

diabetic ketosis) will increase acid in body fluids -> decreased blood pH
o An example of metabolic acidosis is when your leg falls asleep
4. Metabolic alkalosis:
Usually results from:
o An increase in plasma HCO3
o Eliminating too much fluid by frequent urination, by excessive vomiting acidic
gastric contents (HCl loss from the stomach, more HCL is brought into the
stomach from the blood-> Increase blood pH
o Or by ingestion of (lots of) alkaline drugs, such as antacids
o If the body becomes too alkalitic, the nervous system and the heart can be
affected. The heart may speed up becoming irritable while breathing will slow in
order to compensate
5. Effects of acidosis and alkalosis:
Life threatening limits are a pH of below 6.8 and above 7.0 (if sustained is usually fata)
With pH of < 7.0 (acidosis)
o CNS is depressed
o Patient goes into coma and death follows
With pH of > 7.8 (alkalosis)
o CNS is overexcite, leading to muscle tetany, extreme nervousness, and
convulsions, and ultimately death
Fatty Acids and Beta Oxidation
A. With increased fat intake or starvation -> Increased fatty acid and ketone bodies (which may be
too much for Krebs cycle to handle), are spilled into the blood -> which will increase acid in the
system (ketosis). Prolonged ketosis-> metabolic acidosis
1. 1ST STEP Fatty acids are catabolized in mitochondrial matrix:
o They are broken-down to a 2 carbon acetic acid fragment (reduced coenzymes)
o The acidic molecules are fused to coenzyme A and they form two carbon
fragments acetyle coenzyme A (acetyl CoA)
o This process involves a series of reactions (e.g. dehydration, hydration, and
cleavage)
nd
2. 2 STEP In the Krebs cycle
o Acetyle CoA enters and produces ATPs
In the liver
If there is no oxaloacetic acid it forms a substance called acetoacetic
acid, which in turn is converted to acetone and B-hydroxybutyric acid->
ketone bodies will end up in the blood -> acidosis