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Introduction

Cells are the structural and functional units of all living organisms. Some organisms, such as
bacteria, are unicellular, consisting of a single cell. Other organisms, such as humans, are
multicellular,
indicating that humans are made up of many cells (see Figure 2.1). They are the
smallest independent units of life with different parts (see Figure 2.2) that perform their own
function (see Table 2.1). For the cells to survive some fundamental chemical activities occur
within the cell. Some of these activities include cellular growth, metabolism and reproduction.
Each cell is an amazing unit of life; it can take in nutrients, convert these nutrients into energy,
carry out specialised functions and reproduce as necessary. Most amazingly, each cell stores its
own set of instructions for carrying out each of these activities.
Substances such as water, electrolytes and nutrients move in and out of a cell utilising a transport
system. There is constant movement of fluid and electrolytes between the intracellular and
extracellular compartments. The movement of fluid and electrolytes ensures that the cells
receive a constant supply of electrolytes, such as sodium, chloride, potassium, magnesium,
phosphates, bicarbonate and calcium, for cellular function. The cell consists of four basic parts:
•• cell membrane
•• cytoplasm
•• nucleus
•• nucleoplasm.

Cell membrane

Like all other cellular membranes, the plasma membrane consists of both lipids and proteins.

The fundamental structure of the membrane is the phospholipid bilayer, which forms a stable

barrier between two aqueous compartments. In the case of the plasma membrane, these

compartments

are the inside and the outside of the cell. Proteins embedded within the

phospholipid

bilayer carry out the specific functions of the plasma membrane, including selective

transport of molecules and cell–cell recognition.

The cell membrane is a thin membrane that forms the outermost layer of a cell, and it is also

called the plasma membrane. This membrane ensures the boundary and integrity of the cell and

that its contents are separated from the surrounding environment. The cell membrane contains

a variety

of biological molecules, mainly proteins and lipids, which are involved in many cellular

functions, such as cellular communication and cellular transport. The cell membrane is made up

of a double layer (bilayer) of phospholipid (fatty) molecules with protein molecules interspersed

between them (see Figure 2.3). The cell membrane can vary from 7.5 to 10 nm (nanometres) in

thickness (Jenkins and Tortora, 2013).

The phospholipid bilayer consists of a polar ‘head’ end, which is hydrophilic (water loving),

and fatty acid ‘tails’, which are hydrophobic (water hating). The hydrophilic heads are situated on

the outer and inner surfaces of the cell, while the hydrophobic areas point into the cell membrane

(see Figure 2.3) as they are ‘water‐hating’ ends. These phospholipid molecules are arranged

as a bilayer with the heads facing outwards. This means that the bilayer is self‐sealing. It is the

central part of the plasma membrane, consisting of hydrophobic ‘tails’, that makes the cell membrane

impermeable to water‐soluble molecules, and so prevents the passage of these molecules

into and out of the cell (Marieb and Hoehn, 2013). However, substances need to enter and leave

the cells for the cells to survive and function; these are provided by special proteins, such as

integral and peripheral membrane proteins (see Figure 2.3).

The integral transmembrane proteins are attached to the cell membrane and they can form

channels that allow for the transportation of materials into and out of the cell. Examples of integral

transmembrane proteins include voltage‐gated ion channels, such as those that transport

potassium ions in and out of cells, certain types of T cell receptors, the insulin receptor, and many

other receptors and neurotransmitters. On the other hand, peripheral membrane proteins are

Functions of the cell membrane

Cell membranes serve several important functions:

•• They are selective semi permeable membranes, which means that some molecules can diffuse

across the lipid bilayer but others cannot. Small hydrophobic molecules and gases like oxygen

and carbon dioxide cross membranes rapidly. Small polar molecules, such as water and

ethanol, can also pass through membranes, but they do so more slowly. On the other hand,

cell membranes restrict diffusion of highly charged molecules, such as ions, and large

molecules, such as sugars and amino acids. The passage of these molecules relies on specific

transport proteins embedded in the membrane.

•• Membrane transport proteins are specific and selective for the molecules they move, and

they often use energy to catalyse passage. Also, these proteins transport some nutrients

against the concentration gradient, which requires additional energy. The ability to maintain

concentration gradients and sometimes move materials against them is vital to cell health

and maintenance. Thanks to membrane barriers and transport proteins, the cell can

accumulate nutrients in higher concentrations than exist in the environment and, conversely,

get rid of waste products (Figure 2.4).

•• Other transmembrane proteins have communication‐related jobs. These proteins bind

signals, such as hormones or immune mediators, to their extracellular portions. Binding

causes a conformational change in the protein that transmits a signal to intracellular

Cellular fluid compartments

The two principal body fluid compartments are intracellular and extracellular. The intracellular

compartment is the space inside a cell and the fluid inside the cell is called intracellular fluid

(ICF). The extracellular compartment is found outside the cell and the fluid outside the cell is

called extracellular fluid (ECF). However, the extracellular compartment is further divided into```

Intracellular fluid

•• The ICF is primarily a solution of potassium and organic anions, proteins, and so on.

•• The cell membranes and cellular metabolism control the constituents of this ICF.

•• ICF is not consistent in the body. It represents a collection of fluids from all the different cells

Extracellular fluid

•• The ECF primarily consists of NaCl and NaHCO3 solution.

•• The ECF is further subdivided into three compartments:

•• Interstitial fluid (ISF) consists of all the bits of fluid that lie in the interstices of all body

tissues. This is also a ‘virtual’ fluid (i.e. it exists in many separate small bits but is spoken

about as though it is a pool of fluid of uniform composition in the one location). The ISF

bathes all the cells in the body and is the link between the ICF and the intravascular

compartment. Oxygen, nutrients, wastes and chemical messengers all pass through the ISF.

ISF has the compositional characteristics of ECF (as mentioned above), but in addition it is

distinguished by its usually low protein concentration (in comparison with plasma). Lymph

is considered as a part of the ISF. The lymphatic system returns protein and excess ISF to the

circulation. Lymph is more easily obtained for analysis than other parts of the ISF.

•• Plasma is the only major fluid compartment that exists as a real fluid collection all in

one location. It differs from ISF in its much higher protein content and its high bulk

flow (transport function). Blood contains suspended red and white cells, so plasma has

been called the ‘ISF of the blood’. The fluid compartment called the blood volume is

interesting in that it is a composite compartment containing ECF (plasma) and ICF (red

cell water).

•• Transcellular fluid is a small compartment that represents all those body fluids that are

formed from the transport activities of cells. It is contained within epithelial‐lined spaces. It

includes cerebrospinal fluid, gastrointestinal tract fluids, bladder urine, aqueous humour

and joint fluid. It is important because of the specialised functions involved. The fluid fluxes

involved with gastrointestinal tract fluids can be quite significant.

•• The fluid of bone and dense connective tissue is significant because it contains about 15%

of the total body water. This fluid is mobilised only very slowly, and this lessens its

importance when considering the effects of acute fluid interventions.

Snapshot

Loss of fluid and electrolytes through burns

Boon Sew, a 48‐year‐old male, was brought in by ambulance to the emergency department after

being rescued from his burning house. He was asleep at night when a spark from the family fireplace

started a fire, leaving him trapped in his bedroom. By the time the fire rescue team arrived, he

had suffered severe burns and excessive smoke inhalation.

On arrival to the emergency department, he was unconscious. He had second‐degree burns

over 5% of his body and third‐degree burns over 20% of his body – both covering his thoracic and

abdominal regions and his right elbow. His vital signs were quite unstable: blood pressure was

53/35 mmHg; heart rate was 200 beats/min; and respiratory rate was 38 breaths/min. He was deteriorating

from circulatory failure. Two intravenous lines were inserted and fluids and electrolytes

were administered through each. His vital signs stabilised and he was admitted to the intensive

care unit.

Boon Sew regained consciousness the following day and was able to respond verbally. Once his

condition was stable and he was able to respond to treatment, he was transferred to the ward

where he continued to make a good recovery. He was then discharged into the community after

making a full recovery.

Fluid movement between compartments

The movement of fluid between the intracellular and the extracellular compartments is primarily

controlled by two forces:

•• hydrostatic pressure – the pressure exerted by the fluid;

•• osmotic pressure – the pressure that must be exerted on a solution to prevent the passage of

water into it across a selective permeable membrane.

Furthermore, the movement of fluid is dependent on solutes dissolved within the fluid; changes

in the concentration of solutes will affect fluid movement between compartments. Similarly,

changes in fluid volume will also affect fluid movement between compartments. An example of

fluid and solute movement that occurs in the body is when blood pressure (hydrostatic pressure)

forces fluid and solutes from the arterial end of the capillaries into the ISF space (see Figure 2.7).

Fluid and solutes return to the capillaries at the venous end as a result of the osmotic pressure.

Fluid also enters the lymphatic capillaries from the interstitial space as a result of the osmotic

pressure

in the lymphatic vessels.

The movement of fluid between the intracellular and extracellular compartments is the

result of hydrostatic and osmotic pressures. In a normal state of health, the hydrostatic pressure

in the intracellular compartment and the interstitial space is in balance and therefore

the fluid movement is minimal. However, changes in the osmotic pressure either in the intracellular

or extracellular compartments can affect fluid movement. As the capillary barrier is

readily permeable to ions, the osmotic pressure within the capillary is principally determined

by plasma proteins that are relatively impermeable. Therefore, instead of speaking of ‘osmotic’

pressure, this pressure is referred to as the ‘oncotic’ pressure or ‘colloid osmotic’ pressure

because it is generated by colloids. Albumin generates about 70% of the oncotic pressure.

This pressure is typically 25–30 mmHg. The oncotic pressure increases along the length of

Composition of body fluid

Composition of body fluid

The body fluid is composed of water and dissolved substances such as electrolytes (sodium,

potassium and chloride), gases (oxygen and carbon dioxide), nutrients, enzymes and hormones.

The total body water constitutes 60% of the total body weight, and water plays an important

part in cellular function (LeMone et al., 2011). Water is essential for the body as:

•• It acts as a lubricant, which makes swallowing easy.

•• It is also the major component of the body’s transport systems. The blood transports

nutrients, oxygen, glucose and fats to various tissues and cells. Also, the waste products of

cellular metabolism are removed, such as lactic acid and carbon dioxide. Via the urine, a

number of waste products are transported out of the body; for example, urea, phosphates,

sulfites, minerals, ketones from fat metabolism and nitrogenous waste from protein

breakdown.

•• It is needed for regulation of body temperature at 37 °C. When body temperature starts to

rise, blood vessels near the surface of the skin dilate to release some of the heat; the reverse

happens when body temperature starts to drop. Also, when body temperature rises, sweat

glands secrete sweat, which is 99% water. As the sweat evaporates, heat is removed from

the body.

•• It provides an optimum medium for the cells to function.

•• There are chemical reactions in the body which require water. A synthesis reaction

involves the joining of two molecules by the removal of a water molecule, and a

hydrolysis reaction involves a molecule being split into two smaller molecules with the

addition of water.

•• It breaks down food particles in the digestive system.

•• It provides lubrication for the joints as it is a component of synovial fluid. It is also a component

of tears, which lubricate the eyes, and of saliva to provide lubrication to food, which aids

chewing, swallowing and digestion of food. It also has protective roles, washing away

particles that get into the eyes, providing cushioning against shock for the eyes and the

spinal cord. It is also a component of amniotic fluid, which provides protection for the foetus

during pregnancy.

Effects of water deficiency

Deficiency of water in the body can affect various functions, and in severe conditions it might

also lead to death. Some of the problems associated with water deficiency include:

•• low blood pressure

•• increased clotting of blood

•• kidney dysfunction, leading to renal failure

•• severe constipation

•• multisystem failure

•• proneness to infection

•• electrolyte imbalance

Variation in body fluid content

Neonates contain more water than adults: 75–80% water with proportionately more ECF than

adults. At birth, the amount of ISF is proportionally three times larger than in an adult. By the age

of 12 months this has decreased to 60%, which is the adult value. Total body water as a percentage

of total body weight decreases progressively with increasing age. By the age of 60 years,

total body water may decrease to only 50% of total body weight in males, mostly due to an

increase in adipose tissue

Clinical considerations

Dehydration

Dehydration may be caused by restricted water intake, excessive water loss or both. The most

common cause of dehydration is failure to drink liquids. The deprivation of water is far more serious

than the deprivation of food. The average person loses approximately 2.5% of total body water per

day (approximately 1200 mL) in urine, in expired air, by insensible perspiration and from the

gastrointestinal tract. If, in addition to this loss, the loss through perspiration is greatly increased

Transport systems

Cells utilise two processes to move substances in and out of the cell: the passive and active

transport systems. When molecules pass in and out of a cell membrane without the use of

cellular energy it is called a passive transport system. This includes:

•• simple diffusion

•• facilitated diffusion

•• osmosis

•• filtration.

On the other hand, an active transport system requires energy to move substances in and out

of a cell. The active transport systems include:

•• active transport with the utilisation of adenosine triphosphate (ATP)

•• endocytosis

•• exocytosis.

Simple diffusion

The term simple diffusion refers to a process whereby a substance passes through a membrane

without the aid of an intermediary, such as an integral membrane protein (Figure 2.8). Water,

oxygen, carbon dioxide, ethanol and urea are examples of molecules that readily cross cell

membranes by simple diffusion. They pass either directly through the lipid bilayer or through

pores created by certain integral membrane proteins. Small non-polar molecules can diffuse

directly through the plasma membrane. One example of simple diffusion is the exchange of

respiratory gases between the cells of the alveolar sac and the blood in the lungs. The rate of

diffusion depends on several factors, and they are:

•• gases diffuse rapidly and liquids diffuse more slowly;

•• at high temperature, the rate of diffusion is much faster;

•• smaller molecules, such as glycerol, will diffuse much faster than larger molecules, like fatty acids;

•• surface area of the cell membrane over which the molecule can work;

•• solubility of the molecule;

•• concentration gradient.

Osmosis

Osmosis is a process where water moves from an area of volume of high water concentration to

a volume of low water concentration through a selective permeable membrane. A selectively

permeable membrane is one that allows unrestricted passage of water, but not solute molecules

or ions. The relative concentrations of water are determined in the amount of solutes dissolved

in the water. For example, a higher concentration of salt on one side of the cell membrane means

that there is less space for water molecules. Water then will move from the side where there is

the greater number of water molecules through the cell membrane to the other side of the cell

where there are fewer water molecules. This is known as osmotic pressure. The higher the concentration

of the solute on one side of the membrane, the higher the osmotic pressure available

for the movement of the water (Colbert et al., 2012).

The osmotic pressure can be too great and damage the cell membrane; therefore, it is important

for the cell to have a relatively constant pressure between the internal and external environment.

If the osmotic pressure on one side of the cell is greater than on the other side, changes to

the cell could take place resulting in cell damage. A red blood cell placed in a solution with a

lower concentration of solute will undergo haemolysis, and if placed in a fluid with a high concentration

of solutes the red blood cell will crenate (see Figure 2.10). On the other hand, if the

Filtration

Filtration is a process where small substances are forced through a semipermeable membrane

with the aid of hydrostatic pressure. One example of filtration within the human body is at the

capillary end of the blood vessels. With the aid of blood pressure, fluid and solutes are forced

out of the single‐layered cells of the capillaries into the ISF space. Large molecules, such as

proteins and red blood cells, remain in the capillaries. Another example of filtration that occurs

in the human body takes place in the kidneys. Blood pressure forces water and dissolved

waste products, such as urea and uric acid, into the kidney tubules during the formation of

urine (see Chapter 10).

active transport system

The main difference between the active and passive transport systems is that the active transport

system utilises cellular energy to move substances through a semipermeable membrane.

The energy is obtained by splitting ATP into adenosine diphosphate (ADP) and phosphate

(see Figure 2.11). Examples of active transport processes are active transport, endocytosis

and exocytosis.

Active transport

An active process is one in which substances move against a concentration gradient from an

area of lower to higher concentration. The cell must expend energy that is released by splitting

ATP into ADP and phosphate. ATP is a compound of a base, a sugar, and three phosphate

groups (triphosphate). These phosphate groups are held together by high‐energy bonds,

which when broken release a high level of energy. Once one of these phosphate bonds has

been broken and a phosphate group has been released, that compound now has only two

phosphate groups (diphosphate) and there is now also a spare phosphate group. This, in turn,

will join up with another adenosine diphosphate group, so forming another molecule of ATP

(with energy stored in the phosphate bonds), and the whole process continues recurring