Pathophysiology Chapter 8- Disorders of Fluid, Electrolyte, and Acid-Base Balance

Intracellular fluid compartment (ICF)

The fluid contained within all the cells of the body
Contains about 2/3 of the body water in healthy adults
Contains moderate amounts of magnesium and large amounts of potassium
Contains almost no calcium, small amounts of sodium, chloride, bicarbonate, a

Extracellular fluid compartment (ECF)

Contains all the fluids outside the cells, including those in the interstitial spaces and the plasma in the blood vessels
Contains about 1/3 of the body water in healthy adults
Contains large amounts of sodium chloride, moderate amounts of bicarbonate
Con

Most of the water in the body is in the intracellular or extracellular fluid compartment?

Intracellular fluid compartment (ICF)

Potassium

~28 times more concentrated inside the cell than outside
Sodium and potassium rely on transmembrane proteins to cross the lipid bilayer

How does water cross the cell membrane?

Osmosis

Electrolytes

Substances that dissociate in solution to form ions (charged particles)
ex. sodium chloride, NaCl, dissociates to form a positively charged Na+ and a negatively charged CL-
ex. of electrolytes:
Potassium
Sodium
Chloride

Nonelectrolytes

Particles that do not dissociate into ions
ex. glucose, urea

Cations

Positively charged ions

Anions

Negatively charged ions

Cations and anions

May be exchanged for one another, providing they have the same charge
Both the interstitial fluid and extracellular fluid contain equal amounts of anions and cations

Osmosis

The movement of water across a semipermeable membrane
Water diffuses down a concentration gradient from the side that has fewer non-diffusable particles to the side that has more, creating osmotic pressure
The magnitude of the osmotic pressure represents

Osmolality

Refers to the osmotic activity that nondiffusable particles exert in pulling water from one side of the semipermeable membrane to the other

Tonicity

The tension or effect that the osmotic pressure of a solution with nondiffusable solutes exerts on cell size because of water movement

Isotonic solution

Same osmolality as the intercellular fluid
ex. .9% sodium chloride
Cells placed in an isotonic solution will neither shrink nor swell

Hypotonic solution

Lower osmolality than the intercellular fluid
When cells are placed in a hypotonic solution, they swell as water moves into the cells

Hypertonic solution

Greater osmolality than intercellular fluid
When cells are placed in a hypertonic solution, they shrink as water moves out of the cells

Body water constitutes approximately ____% of body weight

60%
ICF= 40%, ECF= 20%

Two major subdivisons of the ECF compartment

Interstitial compartment= 14% of body weight
Plasma compartment= 5% of body weight
Transcellular compartment= 1%

Fluid in the interstitial compartment

Acts as a transport vehicle for gases, nutrients, wastes, and other materials
Produces a reservoir from which vascular volume can be maintained during periods of hemorrhage or loss
Interstitial gel, a sponge-like material supported by collagen fibers, fil

Transcellular compartment

Includes the cerebrospinal fluid and the fluid contained in the vascular body spaces, such as the peritoneal, pleural, and pericardial cavities, and joint spaces
Normally 1% of extracellular fluid, but can increase in conditions such as ascites, in which

Four main forces that control the movement of water between the capillary and interstitial spaces

1. Capillary filtration pressure
2. Capillary colloidal osmotic pressure
3. Interstitial or tissue hydrostatic pressure
4. Interstitial colloidal osmotic pressure

Capillary filtration

Refers to the movement of water through capillary pores because of hydrostatic pressure, rather than osmotic force

Capillary filtration pressure

The pressure pushing water out of the capillary into the interstitial spaces
30-40 mm Hg at the arterial end
10-15 mm Hg at the venous end
25 mm Hg in the middle

Hydrostatic pressure

Pressure that results from the weight of water
Inside the capillaries, the hydrostatic pressure is the same as the capillary filtration pressure, about 30 mm Hg at the arterial and and 10 mm Hg at the venous end

Colloidal osmotic pressure

The pulling force created by the presence of evenly dispersed particles, such as the plasma proteins, that cannot pass through the pores of the capillary membrane

Capillary colloidal osmotic pressure

Osmotic pressure generated by the plasma proteins that are too large to pass through the pores of the capillary wall
Pulls fluid back into the capillary
About 28 mm Hg

Interstitial fluid pressure (-3 mm Hg)
Interstitial colloidal osmotic pressure (8 mm Hg)

Contribute to movement of water into and out of interstitial spaces

Interstitial fluid pressure

Force of fluid in the interstitial spaces pushing against the outside of the capillary wall
Normally negative (-3 mm Hg), contributing to the outward movement of fluid from the capillary
Contributes to the outward movement of water into the interstitial s

Interstitial colloidal osmotic pressure

Reflects the small amount of plasma proteins that normally escape into the interstitial spaces from the capillary

Lymphatic system

Represents an accessory route whereby fluid from the interstitial spaces can return to the circulation
Provides a means for removing plasma proteins and osmotically active particulate matter from the tissue spaces
Without it, excessive amounts of fluid ac

Edema

Palpable swelling produced by an increase in interstitial fluid volume

Factors that can lead to edema

1) Increase of capillary filtration pressure
2) Decrease in capillary colloidal osmotic pressure
3) Increase in capillary permeability
4) Obstruction of lymph flow

Cause of edema- increased capillary pressure

Usually due to increased vascular volume (e.g. heart failure- fluid retention, kidney disease)
Venous obstruction (e.g. thrombophlebitis)
Liver disease with portal vein obstruction
Acute pulmonary edema
Commonly causes dependent enema- accumulation of flu

Cause of edema- decreased colloidal osmotic pressure

Usually due to increased loss of plasma proteins, mainly albumin (e.g. liver failure- impaired synthesis of albumin, kidney diseases- glomerular capillaries become permeable to the plasma proteins, particularly albumin & large amounts of albumin are filte

Cause of edema- increased capillary permeability

When the capillary pores become enlarged or the integrity of the capillary wall is damaged, capillary permeability is increased ---> plasma proteins and other particles leak into the interstitial spaces, pulling fluid out of the capillary into the interst

Cause of edema- obstruction of lymphatic flow

Osmotically active plasma proteins and other large particles that cannot be reabsorbed through the pores in the capillary membrane rely on the lymphatic system for the movement back into the circulatory system
Edema due to impaired lymph flow is commonly

Plasma proteins

Exert the osmotic force needed to pull fluid back into the capillary from tissue spaces
Mixture of albumin, globulins, and fibrinogen
Synthesized in the liver

Albumin

Smallest of the plasma proteins, most abundant
Greatest effect on colloidal osmotic pressure

Third space accumulation

Represents the loss or movement and trapping of ECF in a transcellular space, such as in the pericardial sac, the peritoneal cavity, or the pleural cavity

Effusion

Transudation of fluid into the serous cavities
Can contain blood, plasma proteins, inflammatory cells (i.e. pus), and extracellular fluid

The distribution of body fluids between the ICF and ECF compartments relies on...

The concentration of ECF water and sodium
Water- 90-93% volume of body fluids
Sodium salts- 90-95% of ECF solutes

TBW

Total body water
Young men- ~60% of body weight
Elderly men- ~52% of body weight
Young women- ~50% of body weight
Elderly women- ~46% of body weight
Infants- 75-80% of body weight
Obesity decreases TBW, with levels sometimes as low as 30-40% in adults

Obligatory urine output

Even when oral or parenteral fluids are withheld, the kidneys continue to produce urine as a means of ridding the body of metabolic wastes

Insensible water losses

Water losses that occur through evaporative losses from skin and to moisten the air in the respiratory system
Occur without a person's awareness

Most plentiful electrolyte in the ECF compartment

Sodium (Na+)
135-145 mEq/L
Does not readily cross the cell membrane; as a result, only a small amount is in the intracellular fluid

The major cation in the ECF compartment

Na+
Along with its attendant Cl- and HC03- anions, account for approximately 90-95% of the osmotic activity in the ECF
Thus, serum osmolality usually varies with changes in serum sodium concentration

Most sodium losses occur through...

The kidney
When sodium intake is limited or conservation of sodium is needed, the kidneys are able to reabsorb almost all the Na+ that has been filtered through the glomerulus, resulting in essentially sodium-free urine

Two major physiologic mechanisms for regulating body levels of water

Thirst
Antidiuretic hormone (ADH)

ADH

Controls the output of water by the kidney

Effective circulating volume

The portion of the ECF that fills the vascular compartment and is "effectively" perfusing the tissues
Monitored by sensors that are located both in the vascular system and the kidney

Two things that regulate sodium balance by the kidneys

Sympathetic nervous system
Renin-angiotensin-aldosterone system

Sympathetic nervous system

Responds to changes in arterial pressure and blood volume by adjusting the glomerular filtration rate and the rate at which sodium is filtered from the blood
Also regulates renal reabsorption of sodium and renin release

Renin-angiotensin-aldosterone system

Exerts its action through angiotensin II and aldosterone
Angiotensin II acts directly on the renal tubules to increase sodium reabsorption. It also acts to constrict renal blood vessels, thereby decreasing the glomerular filtration rate and slowing renal

Inappropriate ADH secretion would cause a person to exhibit:

A small volume of urine and low serum sodium

Thirst

The conscious sensation of the need to obtain and drink fluids high in water content
Controlled by the thirst center in the hypothalamus
One of the earliest symptoms of hemorrhage and is often present before other signs of blood loss appear

Two stimili for true thirst based on water needs

1) Cellular dehydration caused by an increase in ECF osmalality
2) A decrease in the effective circulating volume, which may or may not be associated with a decrease in serum osmolality
Sensory receptors, called osmoreceptors, which are located in or near

Third "backup" system for thirst

Production of angiotensin II by the renin-angiotensin mechanism in the kidney
Angiotensin II increases in response to low blood volume and low blood pressure
Elevated levels of angiotensin II may lead to thirst in conditions such as congestive heart failu

Hypodipsia

A decrease in the ability to sense thirst
Commonly associated with lesions in the area of the hypothalamus (e.g. head trauma, meningiomas, occult hydrocephalus, subarachnoid hemorrhage)

Polydipsia

Excessive thirst
Normal when it accompanies conditions of water deficit, but abnormal when it results in excess water intake
Increased thirst/drinking behavior can be classified into two categories
1) Inappropriate or false thirst that occurs despite norm

Vasopressin (ADH)

The antidiuretic hormone
Controls the reabsorption of water by the kidneys
Synthesized in the hypothalamus and stored in the posterior pituitary gland
Increased osmolality ---> nerve impulses from hypothalamus travel to the pituitary gland ---> ant pit re

How ADH exerts its effects

Through vasopressin receptors located in the collecting tubules of the kidney
In the presence of ADH, highly permeable water channels called aquaporins are inserted into the tubular membrane. The increased water permeability allows water from urine to be

ADH acts on the ______ to _______ water excretion

Kidneys; decrease
ADH levels are high---> most or all of the filtered water is reabsorbed and a small amount of concentrated urine is excreted
ADH levels are low---> less water is reabsorbed and dilute urine is excreted

Diabetes insipidus

Caused by a deficiency of ADH or a decreased renal response to ADH
People with DI are unable to concentrate their urine during periods of water restriction and they excrete large volumes of urine- accompanied by excessive thirst
Neurogenic/central DI- occ

SIADH

Syndrome of inappropriate antidiuretic hormone
Results from a failure of the negative feedback system that regulates the release and inhibition of ADH
In people with the syndrome, ADH secretion continues even when the serum osmolality is decreased, causin

Disorders of water and sodium balance can be divided into two main categories

1) Isotonic contraction or expansion of the ECF volume brought about by proportionate changes in sodium and water
2) Hypotonic dilution or hypertonic concentration of the ECF brought about by disproportionate changes in sodium and water

Isotonic fluid volume deficit

Results when water and electrolytes are lost in isotonic proportions
Almost always caused by a loss of body fluids and is often accompanied by a decrease in fluid intake
Often follows loss of GI fluids with severe vomiting, diarrhea, or gastrointestinal s

Isotonic fluid volume excess

Represents an isotonic expansion in the ECF compartment ---> increases both interstitial and vascular volumes
Usually results in an increase in total body sodium accompanied by a proportionate increase in body water
Excessive sodium intake or a decrease i

Hyponatremia

Sodium deficit
Decreased serum sodium osmolality
Dilutional decrease in blood components, including hematocrit, blood urea nitrogen (BUN)
One of the most common electrolyte disorders seen in hospitalized patients
Can present as hypovolemic, (low blood pla

Hypernatermia

Sodium excess
Increased serum sodium osmolality
Increased concentrations of blood components, including hematocrit, BUN
Results in cellular dehydration---> excessive thirst

What is the main determinant of water and sodium balance?

The effective circulating blood volume
Monitored by
-Stretch receptors in the vascular system that exert their effects through thirst, which controls water intake
-ADH, which controls urine concentration

Sodium (Na+)

Most abundant cation (positively charged ion) in the ECF

Chloride (Cl-)

Most abundant anion (negatively charged ion) in the ECF

Potassium (K+)

Most abundant cation in the intracellular fluid- 98% located in ICF
Second most abundant cation in the body
High ICF concentration of potassium is required for many cell functions, including
-Maintenance of osmotic integrity of cells and acid-base balance

Hypokalemia

Potassium deficit
Can result from inadequate intake, excessive losses, or redistribution from the ICF to ECF compartments
Manifested by alterations in kidney, skeletal muscle, gastrointestinal, and cardiac function

Hyperkalemia

Potassium excess
Can result from decreased elimination of potassium by the kidney, a transcellular shift in potassium from the ICF to ECF compartment, or excessively fast IV administration of potassium
Manifested by alterations in neuromuscular and cardia

Hydrogen phosphate (HPO4-)

Most abundant anion in the intracellular fluid

Most water is excreted via the

Kidneys

Aldosterone

Key regulator of sodium reabsorption in the kidney

Which of the following would increase sodium excretion?
-Progesterone
-Glucocorticoids
-Aldosterone
-Estrogen

Progesterone

Calcium, phosphorus, magnesium

The most divalent (two bonds formed) cations in the body
Levels regulated by intestine, kidney, and bone, primarily by the interaction of PTH and vitamin D

Calcium

Most deposited into bone- only a small amount in the ECF
99% of calcium found in the bone, less than 1% in ECF compartment
Of the three forms of ionized calcium, only the ionized form can cross the cell membrane, contributing to
-Neuromuscular function
-B

Hypocalcemia

Decreased levels in ionized calcium
Produces an increase in muscular excitability

Hypercalcemia

Increased levels of ionized calcium
Produces a decrease in muscular excitability

Phosphorous

Like calcium, largely an ICF anion, being incorporated into nucleic acid, ATP, and RBCs

Hypophosphatemia

Abnormally low levels of phosphate in the blood
Associated with:
-Decreased intestinal absorption
-Transcompartmental shifts
-Disorders of renal elimination
Causes:
-Signs and symptoms of neural dysfunction
-Disturbed musculoskeletal function
-Hematologic

Hyperphosphatemia

Abnormally high levels of phosphate in the blood
Occurs with renal failure and PTH deficit
Associated with decreased plasma calcium levels

Magnesium

Second most abundant ICF cation (after potassium)
Acts on many intracellular enzyme reactions
Required for cellular energy metabolism

Hypomagnesemia

Deficiency of magnesium in the blood
Produces:
-Decrease in calcium due to suppression of PTH release
-Decrease in serum potassium due to renal wasting
Both contribute to increase in neuromuscular excitability

Hypermagnesemia

Overabundance of magnesium in the blood
Causes neuromuscular dysfunction, muscle weakness, confusion

Parathyroid hormone

Main function: to maintain extracellular fluid calcium concentrations
-Released in response to low calcium levels
-Causes the release of calcium + phosphorusfrom the bones
-Increased absorption of calcium + phosphorus from small intestine (through its eff

Hypoparathyroidism

Diminished concentration of PTH in the blood
Acute- causes hypocalcemia, manifested by muscle spasms, muscle tetany (cramps)
Chronic- manifested by lethargy and fatigue

Hyperparathyroidism

Abnormally high PTH concentration in the blood
Primary disorder- causing elevated calcium levels and increased excretion of both calcium and phosphorus ---> weak bones, potential for kidney stones
Secondary- associated with chronic kidney disease, exerts

Vitamin D

Synthesized by the skin and converted to its active form, calcitriol, in the kidney
Calcitrol acts on the intestines, kidney, bone and increases calcium and phosphorus concentration
-Stimulates absorption of calcium from the intestine
-Increases calcium a

Acid-base balance

Metabolic activities of the body require precise regulation of acid-base balance as reflected in the pH of the ECF- normally maintained within a very narrow range of 7.35-7.45

Acid

A compound that can dissociate and release a hydrogen (H+) ion

Base

A compound that can accept or combine with H+

Most of the body's acids and bases are...

Weak

H2C03

Weak acid derived from carbon dioxide

HC03-

Weak base

The concentration of hydrogen in body fluids is _____ compared to other ions

Low
Because of this, hydrogen concentration is expressed as pH

pH

Represents the negative logarithm of H+ concentration
Low pH = acidic = high H+ concentration
High pH = alkaline = low H+ concentration

Carbon dioxide

Body metabolism results in a continuous production of carbon dioxide
Diffuses out of body cells and into tissue spaces, then into the circulation

Carbon dioxide is transported into circulation in three forms:

1) Dissolved in plasma
2) As a bicarbonate
3) Attached to hemoglobin

Carbon dioxide dissolved in plasma

Small portion (10%) of CO2 that is produced by body cells is transported in the dissolved state to the lungs and then exhaled
The amount of CO2 that can be carried in plasma is determined by the partial pressure of the gas (PCO3) and the solubility coeffi

Carbon dioxide in bicarbonate

CO2 in excess of that which can be carried into the plasma moves into the RBCs, where the enzyme carbonic anhydrase (CA) catalyzes its conversion to carbonic acid (H2CO3)
The H2CO3 then dissociates into hydrogen (H+) and bicarbonate (HCO3-) ions
H+ combin

Carbon dioxide in hemoglobin

The remaining CO2 in the RBCs combines with hemoglobin to form carbaminohemoglobin (HbCo3)
The combo of CO2 with hemoglobin is a reversible reaction characterized by loose blood, so that Co2 can be easily released in the alveolar capillaries and exhaled f

Regulation of acid-base balance

Metabolic processes produce volatile carbonic acid (H2CO3) in equilibrium with dissolved carbon dioxide (PCO2), which is eliminated through the lungs, and nonvolatile acids, which are excreted by the kidneys

pH in body fluids is regulated by three major mechanisms

1) Chemical buffer systems in body fluids, which immediately combine with excess acids or bases to prevent large changes in pH
2) The lungs, which control the elimination of CO2
3) The kidneys, which eliminate H+ and both reabsorb and generate HCO3-

Respiratory regulation of pH

Relies on ventilation for release of CO2 into the environment
Is rapid but does not return the pH completely to normal

Renal regulation of pH

Rely on the elimination of H+ ions and the conservation of HCO3- ions
Takes longer but returns pH to normal or near-normal levels

Metabolic acidosis

Decrease in pH due to a decrease in HCO3-

Metabolic alkalosis

Increase in pH due to an increase in HCO3-

Respiratory acidosis

Decrease in pH due to an increase in PCO2 levels
Result of elevated blood levels of CO2 due to hypoventilation, shallow breathing, suffocation, or lung diseases that impede O2 and CO2 exchange.

Respiratory alkalosis

Increase in pH due to a decrease in PCO2 levels
Caused by conditions that produce hyperventilation

If you gave a normal patient 1 L of distilled water IV (which you would never do), once that water had equilibrated across the total body water the plasma volume would be expanded by about:

Less than 100 mL

If you gave a normal patient 1 L of isotonic saline IV, once that fluid had equilibrated across the total body water the intracellular volume would be expanded by about:

0 mL

Which of the following would NOT cause edema:
a) a decrease in arterial blood pressure.
b) an increase in venous blood pressure.
c) a decrease in albumin production by the liver.
d) an increase in capillary permeability to proteins.

a) a decrease in arterial blood pressure

Inappropriate ADH secretion would cause a person to exhibit:

A small volume of urine and low serum sodium

A person who is dehydrated because of lack of water access would exhibit:

A small volume of urine and high serum sodium

A person with untreated diabetes insipidus would exhibit:

A large volume of urine and high serum sodium

In diabetic ketoacidosis we expect to see a:

A low serum bicarbonate level and a low pH

Which of the following would be most likely to produce a small reduction in pH with an elevated PCO2 and an elevated serum bicarbonate?

Chronic emphysema

Buffers

A substance that consists of acid and base forms in a solution and that minimizes changes in pH when extraneous acids or bases are added to the solution.
At least 3/4 of the body's buffering capacity is via intracellular proteins