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INTRODUCTION

INFUSION THERAPY AND B|BRAUNB|BRAUNB|BRAUNB|BRAUN

While in the USA the development of Infusion therapy was characterised by names

like Donald Baxter or Foster McGaw, in Germany it was inseparably associated with

Dr. Bernd Braun and consequently with B. Braun Melsungen AG. In the field of

infusion solutions comprising trade-marks as Stereofundin® or Plasco® as well as

with the introduction of medical products such as Braunula®, Intrafix® and

Perfusor®, B|BRAUN set milestones in the development of application techniques

that have nowadays become routine. Also with regard to economical aspects, thedevelopment of infusion therapy is closely connected to the rise of the company to

one of the leading hospital suppliers in Europe since more than half of the total

turnover is achieved by sales out of the various product lines for infusion therapy.

HISTORICAL DEVELOPMENT

The discovery of the blood circulation by William HARVEY in 1628, reported in his

"Exercitatio anatomica de motu cordis es sanguinis in animalibus" served as the

physiological-anatomical basis for the clinical use of intravenous injection, infusion

and transfusion. The first practical injection trials in animals were, however, not

carried out by physicians, but rather by laymen. The cavalry captain, VAN

WAHRENDORF, injected wine into the veins of his hunting dogs and observed the

typical symptoms of drunkenness in them. Further trials are reported from England.

WREN carried out intravenous injections in animals in 1656, WREN, BOYLE and

CLARKE continued these experiments in the following years, using a small tube to

which an animal bladder was attached. The substances injected included among

others water, wine, milk, beer, opium solutions, meat bouillon, emetics. The

physicians Johann Sigismund ELSHOLTZ, Johann Daniel MAJOR and Michael

ETTMÜLLER introduced the technique of intravenous application of drugs for

therapeutic purposes in Germany.

In 1657 Robert BOYLE carried out the first blood transfusion followed by Jean DENIS

in 1667. While in the first case blood was transfused from one animal to another the

second one was the very first case where a sheep’s blood was transfused to ahuman being (fig. 1). Further descriptions were provided by LOWER and KING, 1667

and GAYANT, 1667/1668. In the 18th century intravenous injections were carried out


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in physiological and pharmacological trials as well as for therapeutic purposes,

however, without the final medical breakthrough being yet to come. Though some

very few cases of successful injection were reported, the side effects acted as a

significant deterrent.

All in all, the medical profession remained rather reticent during the first half of the

19th century. Though bloodletting, rectal syringes and cannulae had been known

since antiquity, the technique of intravenous injection had posed a major problem to

the physicians since the 17th century as can be gathered from the variety of methods

recommended. The most serious problem to cope with was how to inject fluid into the

vein of a patient through the bloodletting wound used for this purpose. The English

surgeon HUNTER is reported to have mentioned a sharpened hollow needle for the

first time in 1830. During the second half of the 19

th

century, the newly inventedtechnique gave the first major impetus to the method of intravenous injection for

therapeutic use.

In 1853 Karl PRAVAZ described a glass syringe with a hollow needle attached to it.

The piston was driven forward by means of a thread. He tried to thrombose the

aneurysm of a peripheral artery by injecting iron chloride. In 1858 WOOD published a

report on a graduated glass syringe to which a thin, hollow needle was attached. In

1869, LUER constructed a piston syringe made of glass with a cone for attaching the

needle.

In 1881 LANDERER finally succeeded in introducing the method of intravenous

injection to clinical practise by using the PRAVAZ syringe. He recommended a

technique that did not involve prior venae section to expose the vein, but to puncture

it through the intact skin following compression. The discovery of the blood groups by

Karl LANDSTEINER in 1901 also provided the basis for modern blood transfusion. In

1906 the record syringe, made of glass and metal, was introduced in Germany.

Administration of drugs by way of infusion, however, did not become a commonly

used technique until Albert FRÄNKEL introduced strophanthin in 1906 and Paul

EHRLICH introduced salvarsan in 1910. The therapeutic use of these two drugs

contributed to physicians becoming familiar with the method of intravenous injection.

While shortly after the second world war infusions were still carried out only in cases

of severe illness, often using self-made devices, they are nowadays one of the

indispensable therapeutic methods in modern clinical practice. Since 1960 single-use

articles meeting the highest technical standards and medical requirements have

replaced multiple-use products for reasons of hygiene and rationalisation. With thesenew products, an i.v. infusion requires only little more effort than any other i.v.

injection.


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INFUSION THERAPY TODAY

Today infusion therapy is of considerable importance in intensive-care medicine,

serving as a method for the intake of water, electrolytes, blood and substrates. It isalso used for the intravascular administration of drugs as well as for diagnostics. The

parenteral administration of drugs is thus a routine form of application in clinical

therapy. In modern intensive care medicine, for example, the patient receives

parenteral nutrition as well as all drugs which are necessary for treatment by way of a

central line catheter.

All in all, infusion therapy plays a highly important role in modern medicine. In

particular, clinical anaesthesia, reanimation, intensive care therapy and emergency

medicine would not be possible without it.


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PURPOSE OF THE LECTURE NOTES

The lecture notes “Background Information on INFUSION THERAPY” are designed

for training internal B|BRAUN staff as a means of preparation prior to the seminar.Two goals are important here: On the one hand, learning beforehand shall establish

a common level of knowledge among the participants so that during the seminar

attention can be focused on practical examples. On the other hand, when working

through the notes, individual gaps of knowledge can be found that will be eliminated

during the seminar.

The lecture notes could help healthcare professionals to prepare their own lectures or

students to understand the principles of infusion therapy.

STRUCTURE OF THE LECTURE NOTES

The present lecture notes are divided into two sections. The first part comprises

background information on biological structures and the function of the body. This

basic knowledge is indispensable for the understanding of infusion therapy. The

second part finally deals with the essential elements of infusion therapy serving as a

lead-in to the complex field of this therapy .

As these lecture notes should serve as a learning tool, they include some elements

which support the learning process.

! The training objectives stated at the beginning of each chapter give an overview

of the material that shall be worked through in this chapter.

! At the end of the chapters there are comprehension questions which help to

control one’s own learning success

! In the annex of the script you will find a glossary giving the most important

technical terms. The terms explained in the glossary are underlined in the text.


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ΙΙΙΙ

BIOLOGICAL BACKGROUNDINFORMATION

ON INFUSION THERAPY

This part contains basic information on biological structures and the processes of the

body. This basic knowledge is an indispensable prerequisite for comprehending the

complex field of infusion therapy. Each infusion means a surgical intervention into the

biological mechanisms. That is why comprehension of infusion therapy requires a

solid basic knowledge of biology.

Out of the complexity of existing structures in the human organism only those will be

explained that directly relate to the topic of infusion therapy. First of all the basic

building block of all life – the cell – is described. Beside the basic composition of the

cell the most important cell structures will be explained The following chapter

presents information about blood, describing the main tasks of blood, its single

components as well as the process of blood coagulation. In the following the

cardiovascular system is described including a short explanation of heart and vessels

as well as the existing pressure conditions. Further, the most important components

and processes of the water balance are described. The first section closes with a

chapter about the basic elements of the nutrition of the organism.


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1THE CELL

The cell (lat. Cellula = small chamber) is considered to be the basic building block of

all life. The organism consists of a number of cells. They are the elementary

structural and biological units of the body and are the basis of its functions. Every cell

type is specialised for a particular job in the organism. It constantly exchanges

energy and substances with the surrounding milieu. It can nourish itself, grow,

reproduce and react to stimuli from its surroundings. Following a survey of the

general cell components, these lecture notes give details of the most important

structures of the cell.

1.1 General Cellular Structure

The basic parts of the cell are A) the cell body (cytoplasm or protoplasm) and B) the

cell nucleus. The cell membrane (plasma membrane) separates the cell from its

surroundings. The cytoplasm consists of a variety of highly organised bodies, called

organelles. Important organelles are, for example, the mitochondria.

PLEASE NOTE:There are also cells without a nucleus, the erythrocytes (red

blood cells); only during the initial state do they have a

nucleus, and are called reticulocytes (see 2.2 The Blood)

Training Objectives:" Knowledge of the general cell components

" Short description of the most important cell structures


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Fig. 1: The cell

1.2 Important Cellular Structures

In the following, the most important cell structures are explained; these can be seen

with the help of an electron microscope. Some of the cell structures are also shown infig. 1.

The cell body

The cell body is also called cytoplasm or protoplasm. It consists of protein, H2O,

salts and metabolites.

The cell membraneThe cell membrane consists of the three outer layers of the cell: The

semipermeable cell membrane protects the cytoplasm from damaging

influences; it functions as a filter.

Nucleus (or karyosome)

When not being in the state of division, it consists of a nuclear membrane, one

or more nucleoli, and an achromatic nuclear reticulum (does not take on dyes)

containing the chromatin and the karyolymph.


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The nuclear membrane

Forms a definite border between the nuclear substance and the surrounding

cytoplasm.

The nuclear reticulum

The interior of the nucleus contains nucleic acids (desoxyribonucleic acid -

DNA). DNA contains the chemical substances that characterise the

chromosomes (soma = body), the carriers of inherited characteristics

(genes).

Karyolymph (nuclear sap)

The gaps between the single parts of the nuclear reticulum are filled with a

clear basic mass, the karyolymph. It plays a role in the changes of the

nucleus’s shape, the transport within the nucleus and between nucleus and

cytoplasm.

Nucleoli

They carry metabolic substances and reserve substances for protein

synthesis.

The cytological organelles

Cytological organelles are cytocentres that are usually located right near the

nucleus. The cytocentres are very important for the process of cell division

(mitosis).

The mitochondriaBy means of certain enzymes (protein molecules that affect chemical

reactions, speeding them up without themselves being changed), the

mitochondria are responsible for correct oxidation processes in the cell. They

supply the cell with the energy required for metabolism. The mitochondria are

located where energy-consuming processes take place.


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Golgi’s apparatus (Dalton complex)

Golgi’s apparatus is also located near the nucleus. It consists of fat and

protein substances. It plays an important role in the secretion mechanism of

the cell.

1.3 Summary

The cell is considered to be the basic building block of all life.

The cell components are differentiated by the cytoplasm (cell body) and the nucleus

(cell nuclear). The cell is protected against its surroundings by means of the cell

membrane. However, it is in constant energy- and metabolic interaction with its

surroundings.

1.4 Comprehension Questions

! Why is a basic knowledge of biology an indispensable prerequisite for the

understanding of infusion therapy?

! What rough differentiation regarding the cell structure can be applied?

! What function does the cell membrane have?

! What function does the mitochondrion have?


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2

THE BLOOD

The blood is an organ system; its cells float in fluid. All organs of the body form a

functional unit through the mediation of the blood. First of all blood is a means of

transportation. The following is a description of important functions of the blood and

its components. It should be borne in mind, that size and form of the blood

components play an important role in infusion therapy. The chapter closes with a

presentation of the blood clotting process.

2.1 Functions of the Blood

The balance in the interior milieu is called homeostasis. Every cell contributes to the

homeostasis and profits from it at the same time. The blood is of particular

importance for the homeostasis. The human being shows a highly sensitive reaction

to the slightest change of certain blood parameters such as pH-value, theconcentration of the blood-sugar-value or the temperature of the blood.

The blood has got the following important functions:

! Transport of substances, i.e. nutrients and oxygen are transported to the cells

and tissues of the body. Catabolites (such as carbonic acid, water, urine and

CO2 ) are transported to the excretory organs.

! Maintenance of a constant body temperature.

! Maintenance of a constant concentration of hydrogen ions (pH value of 7.42),electrolyte ions and thus isotonicity.

Training Objectives:

! Explanation of the functions of the blood

! Identification of the blood components, arrangement of

the components, description of the most important characteristics (function, size, etc.)

! Knowledge of the blood clotting phases


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! Protective and defence funct ions against invading micro-organisms.

! Closure of a wound.

2.2 Blood Composition

Blood makes up about 7.6% of the whole bodyweight; that means there are

approximately 4-5 litres, with about 3.5 litres constantly in circulation.

The blood is composed of formed parts and the blood plasma. The volume proportion

between the red blood cells and the fluid blood components is called packed cell

volume or haematocrit. An overview of the different substances of the blood are

shown and explained in fig.2.

Blood 4 - 5 litreBlood 4 - 5 litre

Formed components 45%Formed components 45% Blood plasma 55%Blood plasma 55%

Erythrocytes

4,5-5 million/mm 3Erythrocytes

4,5-5 mi llion/mm3

Thrombocytes

200.000-300.000 mm 3Thrombocytes

200.000-300.000 mm 3

Leukocytes

4,5-5 m illion/mm3Leukocytes

4,5-5 m illion/mm 3

Granulocytes60%

Granulocytes60%

Monocytes4%

Monocytes4%

Lymphocytes36%

Lymphocytes36%

Blood serumBlood serum FibrinogenFibrinogen

Figure 2: Blood Composition


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2.2.1 STRUCTURED COMPONENTS

Erythrocytes, leukocytes and thrombocytes (platelets) are the formed components of

the blood.

Erythrocytes: (red cells)

! Number: 4.5 – 5 Mill/mm³

! Appearance: Round, bi-concave discs ,2 µm thick at the edges, 1 µm thick in the

middle, and 7.5 µm in diameter.

! Composition: Each erythrocyte consists of 63% water and 37% dry substance,

mainly haemoglobin (red blood pigment). Haemoglobin is a protein compound

containing iron (Fe2+) that transports oxygen and carbon dioxide.

! Function: Supply the body with oxygen.

! Characteristics: They are characterised by a high plasticity allowing them to

pass through even very small capillaries with a diameter of 5 µm.

! Place of origin: In adults they are formed in the flat bones (shoulder blade,

breastbone, hip bone). During the maturation phase in the bone marrow they lose

their nucleus.

Leukocytes (also called whi te blood cells)

Leukocytes fend off the attempts of invasion by bacteria and viruses for a life time.

Their number is ca. 4,500-8,000/mm³. There exist granulocytes and lymphocytes

(basic-type) as well as monocytes.

Granulocytes

! Number: They represent the largest share of the white blood count

(approx. 60%)! Size: approx. 10 µm in diameter

! Function: They are able to devour micro-organisms (e.g. bacteria). They

are therefore also called macrophages or phagocytes.

! Characteristics: They can also use amoeboid motion to leave the

bloodstream actively and penetrate tissues.

! Place of origin: They are produced in the red bone marrow


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Lymphocytes

! Number: In adults they make up 36% of all white blood cells.

! Size: approx. 7-9 µm in diameter ! Function: They produce antibodies against foreign substances. They are

capable of recognising invading pathogens and are therefore also termed

memory cells.

! Characteristics: They are only capable of limited amoeboid movement and

cannot carry out phagocytosis.

! Place of origin: They are formed in the ”lymphoid” organs (spleen and

lymph nodes).

Monocytes

! Number: They make up approx. 3-6 % of all white blood cells

! Size: They are the biggest blood cells (about 20 µm in diameter)

! Function: They eliminate foreign substances mainly with chronic infections.

! Characteristics: They move out of the blood into the tissues and settle

down there, while gaining in size.

! Location of genesis: They are also produced in the red bone marrow.

Thrombocytes (platelets)

! Number : 150,000 – 300,000/mm³

! Appearance: They are extremely small (1-3 µm in diameter); They are

variable in form.

! Function: They form a clot (thrombus) by means of apposition when a

vessel is damaged.

! Characteristics: The thrombokinase, an important element in the blood

clotting process, is released upon thrombocytolysis (see chapter 2.3 Blood

Coagulation).

! Place of origin: They are also produced in the red bone marrow.


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2.2.2 BLOOD PLASMA

The blood plasma consists of fluid components (blood serum) and firm components(for example fibrinogen)

! Composition: The plasma contains 90% water, 7-8% proteins, fats, lipoids,

enzymes, hormones, pigments, mineral substances and the entire amount of

nonprotein nitrogen.

! Function: The plasma water is the ideal means of transportation for all water-

soluble substances.

! Function of the protein substances: The protein substances (albumin,

globulins) are active in defence functions, but also in the binding of water andthus electrolytes (salts, sodium, potassium, calcium, chlorides). These complex

mechanisms also maintain the blood within a slightly alkaline range (pH = 7.42).

Important The electrolyte concentration in blood corresponds approx.to a 0.9% sodium chloride solution (normal saline).

2.3 The Blood Coagulation

The task of the numerous complex factors necessary for blood clotting is to ensure

that the clot is limited to the site of injury and does not have any life-endangering

effects.

The process of blood clotting is divided in 3 phases:

1st

phase

Normally prothrombin is a constituent part of the blood. Its formation in the liver

involves vitamin K. Because of the destruction of the tissues and the decay of

the clotting blood platelets, the enzyme thrombokinase is activated. With the

participation of disintegrated thrombocytes, electrically charged calcium ions

and various coagulation factors (13 factors are differentiated at present),

prothrombin is converted into thrombin. The blood activator and tissue activator

are also involved.


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2nd

phase

The thrombin produced in this way transforms the fibrinogen in the blood

plasma into fibrin. This forms a fibrilliform mesh enclosing blood cells. In fact

this is the reason for the blood clotting (the thrombus).

3rd

phase

The fibres of the fibrin mesh and are contracted (retraction). The blood clot is

differentiated from the fluid pressed out (blood serum = plasma minus the

coagulation factors).The fibrous mesh solidifies and can then close a small

defect in the vascular wall.

The blood clotting process is followed by the fibrinolysis (lysis = dissolution). Normal

blood plasma also contains the precursor of the enzyme fibrolysin, which can

redissolve a clot. Normally, there is a balance between fibrin formation and

fibrinolysis.

2.4 Summary

The blood has a number of important functions: transport of oxygen, maintenance of

body temperature, maintenance of the hydrogen ion concentration as well as

protection and defence activities.

Blood consists of formed components and blood plasma, this proportion is called

packed cell volume. The formed components are erythrocytes (oxygen supply),

leukocyte (defence against foreign substances) and thrombocytes (thrombus

formation). Besides these different functions the named components differ withregard to the following characteristics: Number, appearance, components and

genesis. Size and plasticity play an important roll in infusion therapy.

The blood plasma consists of firm and fluid components. The firm components are

first off all proteins. Beside defending activities, their function is the binding of water-

and electrolytes. It is also important that the concentration of sodium ions and

chloride ions in the blood is approx. equivalent to a 0.9% sodium chloride solution.

The process of blood coagulation is divided into three interconnected phases,

followed by the fibrinolysis.


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3

THE CARDIOVASCULAR

SYSTEM

The cardiovascular system describes the course taken by the blood from the heart

through the arteries, capillaries, and veins back to the heart. The different parts of the

cardiovascular system are characterised by very different pressures. These

pressures are very important for infusion therapy since they require different technical

devices to bring fluid into the vessel concerned.

Fig. 3: The cardiovascular system

Learning objectives:

! Description of the cardiovascular system

components including the functions! Knowing of the pressure rate in the veins, arteries

and capillaries.

Veins

Venules

Capillaries

Arteries

Arterioles


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3.1 The heart

The heart is the beginning as well as the end of the blood’s circulation. It is a hollow

muscular organ having a suctive and compressive function. In a human being theheart has four chambers: right atrium, left atrium, right ventricle and left ventricle.

3.2 The vessels

The Veins

The veins are vessels transporting blood back to the heart. They are thin walled

and have only low elasticity. The venous valves serve as a reflux stop. Small

venous valves are integrated In the big trunk veins. Venules are fine branchesof the veins.

The largest vein of the body is the vena cava. The central venous pressure

(CVP) is measured here, which is an indicator for the volume contained within

the cardiovascular system. It indicates hidden bleedings or wrong infusion rates.

As an exception, the pressure is measured in ”cm water column” instead of

”mm Hg”. Normally it is about 2-10 cm water column. In the trunk veins the

pressure is approx. 10 mm Hg. The pressure in the venules is about 15 mm Hg.

The Arteries

They are the vessels with the thickest wall in the vascular system and serve to

transport the blood away from the heart. Pressures are 120-160 mm Hg.

Arter io les are finer branches of the arteries. The pressure is about 33 mm Hg.

The Capil laries

Capillaries are small blood vessels connecting the arteries and veins. Theycome out of small arterioles and lead to the smallest venules. Their diameter is

approx. 5 µm.

The capillaries are surrounded by tissue fluid (lymph). Their walls are flimsy and

permeable. There is a permanent gas and oxygen exchange between the

blood, the capillaries and the lymph. The pressure in them is approx. 15-30 mm

Hg. The filtration pressure here exceeds 10 mm Hg.


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3.3 Summary

The cardiovascular system is the way of the blood through the arteries, capillaries

and veins back to the heart. The heart is the beginning as well as the end of the

blood circulation. The thick-walled arteries lead the blood away from the heart; the

blood returns through the thin-walled veins. The capillaries connect the arteries and

the veins.

The different parts of the cardiovascular system are characterised by very different

pressures. Those pressures are very important for infusion therapy.


! What pressures predominate in the different cardiovascular vessels? What role do

these rates play in infusion therapy?

! What is the ”central venous pressure” (CVP)?


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Intracellular Space (ICS)

All metabolic processes in the somatic cells occur within an aqueous milieu.

Extracellular space (ECS)

Outside the cells, water serves as a means of transport to and from the cells

and as a solvent for the somatic colloids. The extracellular space is further

divided into the:

Interstitial part

All cells are separated by fine spaces. These extracellular spaces are called

interstitial. They warrant that all body cells are rinsed by the same fluid, which

contains the necessary salts and nutrients for the supply of the cells.

Intravascular part

The intravascular part is the plasma water.

Table 1: Distribution of body fluid and fluid percentage of body weight for men,

women, and children

Men Women Children

Total body fluid 60 % 50 % 75 %

Intracellular space (ICS) 40 % 30 % 48 %

Extracellular space (ECS) 20 % 20 % 27 %

Interstitial part 15 % 16 % 22 %

intravascular part 5 % 4 % 5 %

Important The fluid spaces are separated from one another bothfunctionally and anatomically.


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4.2 Salts

Human body fluids contain various salts, which dissociate in the aqueous solution

into charged particles (ions). The dominant salt contained in the extracellular fluid is

dissolved sodium chloride. (approx. 9 gr. per litre). We distinguish between positively

charged ions (cations) and negatively charged ions (anions), which are listed in

table 2. Besides these, there are other dissolved substances such as glucose, urea,

creatinine.

Table 2: Cations and Anions

Positively charged ionsCations (+)

Negatively charged ions Anions (-)

Sodium, Na+

Potassium, K+

Calcium, Ca2+

Magnesium, Mg2+

Hydrogen, H+

Bicarbonate, HCO3-

Chloride, Cl-

Phosphate, HPO4--

Proteins

Organic acids

The electrolytic mixture and concentration differs among the fluid spaces. The

organism is always working to maintain constant levels of water and electrolyte

distribution. Various mechanisms for the operation to maintain this homeostasis

(balance) are described in the following.

4.3 Osmosis

Osmosis is the passage of a component in one phase through a membrane into

another phase. Semipermeable membranes are only passable for certain

components, while other components cannot pass.

The cell walls are semipermeable membranes, i.e. structures that allow water

molecules to pass through, but not dissolved particles.. When, for instance, the

extracellular electrolyte concentration rises, water diffuses out of the cell, raising theintracellular concentration level and diluting the extracellular fluid.


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In fig. 4 the process of osmosis is explained: Water diffuses freely through the

semipermeable membrane (M), while the main direction of flow is from the less

dense (less concentrated) solution (B) into the denser (more concentrated) solution

(A) - see arrow.

Figure 4: Diagramme of osmosis. The concentration of the solute in the fluid is shown

by the black dots, which indicate the dissolved particles.

4.3.1 OSMOTIC PRESSURE

This pressure is determined by the total number of ions and molecular components

contained in a solution. It is measured in milliosmoles (mOsm). The total osmotic

concentration of the plasma (fluid part of blood) is approx. 280 mOsm/l.

Solutions which have the same osmolarity as plasma are called isoosmotic; Solutions

with a higher osmolarity are hyperosmotic and those with lower osmolarity are called

hypoosmotic.

Table 3: Osmotic pressure in plasma:

300 mOsm/l = isoosmotic

More than 300 mOsm/l = hyperosmotic

Less than 300 mOsm/l = hypoosmotic


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4.3.2 COLLOID-OSMOTIC OR ONCOTIC PRESSURE

A further mechanism for the distribution of fluids in areas, is the colloid-osmotic (or

oncotic) pressure. This means the ability of dissolved protein particles to bind water.

The intravascular space is particularly rich in proteins due to the blood plasma

content, so that water is maintained. About 90% water lost into the interstitial space

at the arterial end of the capillaries is taken back at the venous end.due to this effect

(the other 10% flow through the lymphatic system back into the vena cava). If the

blood plasma protein level drops too low an accumulation of fluid inside the interstitial

space (oedema) will be the consequence.

4.4 pH-Regulation

(Regulation of the acid-base balance)

Definition: pH = unit of measure for the concentration of hydrogen ions in aqueous

solutions; these ions determine the acid/base content of the solution.

! Acidic solutions have a pH below 7.0 (and down to not more than 0) and have an

excess of hydrogen ions.

! Basic solutions have a pH above 7.0 (to a maximum of 14). These solutions are

capable of absorbing hydrogen ions.

The pH of blood corresponds to the hydrogen concentration (H+ - ion concentration)

in the plasma and indicates the acid-base content As given in fig. 6, the normal pH-

in the human arterial blood is 7.40. Also shown is the normal physiological range

(7.35 – 7.45) as well as the values for acidosis and alkalosis (see glossary).


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Figure 6: Acid-Base Balance

Normally, the kidney and lungs are responsible for excreting an excess of acid and

basic substances. In case one or both of these two organs fail or if the organism

suffers from an excess of acid or base or loses large amounts of either, a deviation

from the normal value occurs, i.e. a pH shift. The balanced state must be reinstatedas soon as possible: The body activates its buffer systems.

These systems are capable of giving off or binding H+ ions as required. This buffer

capacity is, however, exhausted after a certain period of time. Buffer substances are

proteins, bicarbonate, phosphate, and haemoglobin. The most important buffer

substance is the bicarbonate HCO3-, which is released during breathing.

Normally both mechanisms, buffering and excretion of H+ - ions, lead to a constant

pH. If they are no longer capable of doing so, the acid-base balance is disturbed anda pH-shift occurs. If this is due to a pulmorary failure (related to the breathing

apparatus), we speak of a respiratory acidosis or alkalosis; otherwise these are

described as metabolic conditions.

Acidosis Alkalosis


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4.5 Hormonal Regulation

The interaction of various hormones enables the body to maintain a constant balance

of water and electrolytes as long as losses are replaced. If the capacity of the body's

regulatory mechanisms is strained, the fluid and electrolyte balance is disturbed.

4.6 The Water Balance in a Healthy Person

As already said, water makes up approx. 60 % of the total weight of an adult human.

This water content is kept constant in an extremely exact manner. Water intake and

output are possible in different ways. Fig. 7 gives a survey of the average water

intake and output of an adult.

700 ml

1000

bis

1500

ml

300 ml

Food

Drinks

Oxydation waterr (resulting from oxidation of

calorific substrates)

Intake Output

100 ml

1000

bis

1500

ml

stool

urine

Lungs

Skin

+

400 ml

500 ml

Total 2000 - 2500 ml 2000 - 2500 ml

Unnoticed output

water (perspiratio

insensibilis)

Figure 7: The average adult water intake and output.

4.6.1 INTAKE OF FLUID

Normally, the fluid cycle in a healthy adult involves 2-3 l per day. Intake does not onlyinclude drinks, but also water in solid food (pre-formed water) as well as water

resulting from oxidation (oxidation water). Most of the intake, however, is accounted


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for by the daily amount drunk - approx. 1 1/2 l. Intake is the sum of the following three

volumes (see table 4). The water contained in solid food has considerable influence

on the body's drinking requirements.

Table 4: Drinking water, pre-formed water, oxidation water in comparison

Drinking water Pre-formed water Oxidation water

4 2 1

Drinking water is quickly absorbed into the plasma compartment. If no solid food

intake takes place, this process requires less than 1 hour. A direct consequence is an

increase in blood volume and blood pressure, leading to the opening of inactivated

capillary segments and venous vessels in the liver and spleen. Following this, water

enters the interstitial space and finally, since the increased interstitial water volume

lowers the osmotic pressure in this space, it enters the cells.

The behaviour of the kidneys during this adaptation period depends on the fluid

status prior to fluid intake. Given a prior haemoconcentration (thick blood) situation

due to lack of fluids, the kidneys do not begin to excrete until all three compartments

(plasma, cells, interstitial space) have reached their normal volume levels. Excessivefluid intake is of course excreted immediately by the kidneys.

4.6.2 REMOVAL OF FLUID

Fluid excretion is regulated mainly by the kidneys. The other excretion pathways are

not as much in evidence, but are nonetheless of vital importance. Whereas water is

excreted in liquid form together with stool and urine, water vapour is removed from

the body through the lungs. Water is also given off through the skin, usually in theform of vapour. Water loss through the skin can also take the visible form of

perspiration when the body overheats. "Perspiratio insensibilis" is the term used for

the unnoticed loss of fluid via skin and lungs. It amounts to approx. 1 l per day.

This level is raised by a further 500 ml per degree of fever.


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4.6.3 SHIFTS IN GASTROINTESTINAL FLUID BALANCE

A special fluid balance exists between the blood plasma and the digestive tract

secretions, which are formed of plasma as well. The total amount of fluids separatedout in the intestinal tract may reach 8,200 ml in 24 hours. Fig. 8 explains the loss of

fluid types and their constituent amount.

This large amount of fluid is reabsorbed through the mucosa of the large and small

intestines into the bloodstream. This explains the fact that prolonged periods of

vomiting or diarrhoea can lead to death within hours unless the lost fluid is replaced.

This can be avoided by a massive infusion intake.

Figure 8: Fluid types (with constituent amount) that are lost because of vomiting and

diarrhoea.

Saliva (1500 ml)

Gastric juice (2500 ml)

Gall (500 ml)

Pancreatic juice (700 ml)

Small intestine secretion (3000 ml)


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4.7 Summary

The human water and electrolyte balance plays a central role in infusion therapy. Thecellular and tissue structures divide the organism into various segments containing

water or aqueous solutions. We distinguish between intracellular and extracellular

areas. Here again the extracellular area is divided into interstitial and intravascular

parts.

The fluid parts are functionally and anatomically separated. The electrolytic mixture

and concentration differ among the fluid spaces. The organism is always working to

maintain constant levels of water and electrolyte distribution. Various mechanisms

operate to maintain this homeostasis (balance): The osmosis (passing of water through water permeable membranes that won’t let dissolved substances pass),

mechanisms of the pH-regulation (excretion and activation of the buffer systems) and

hormonal regulation.

The share of water in the human weight is very high (approx. 60%). The water intake

is based on the intake of drinking water, pre-formed water and oxidation water. The

fluid output takes place through urine, stool and unnoticed water output through the

lungs and skin (”perspiratio insensibilis”). The water balance is kept constant in an

extremely exact manner. A special situation of fluid constancy exists between the

blood plasma and the secretions of the alimentary tract. Diarrhoea and prolonged

periods of vomiting can lead to death within hours unless the lost fluid is replaced by

infusion therapy.


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! Name the different areas in the body in which water or aqueous solutions are

present.

! What are the percentage amounts of body fluids in the different areas?

! Name the most important cations and anions in the human body fluids.

! Shortly explain the most important mechanisms which can be used for the

maintenance of homeostasis.

! How high is the osmotic pressure of the blood plasma? How do you call thepressure increase or decrease?

! What is the normal pH-value in a human artery? What is an acidosis or an

alkalosis?

! What happens with the buffer systems during a pH-shift?

! Name the most important buffer substances in case of a pH-shift.

! Explain the average water intake and output of an adult!

! What is the ratio between drinking water, pre-formed water and oxidation water?

!!!! Describe the possible consequences of fluid constancy between blood plasma

and the secretions of the alimentary tract.


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5

NUTRITION OF THE BODY

In all phases of life the human body is in need of a constant supply of nutrition, in

order to ensure growth or to maintain the normal bodily functions.

This chapter will provide information about the nutrients the human body needs as

well as about the functions of the single nutrients. The consequences arising from a

deficit of certain nutrients will be shown. You will get to know some mechanisms the

body is able to activate in order to compensate these deficits for at least a short

period of time. In this context the differentiation between essential and conditionally

essential nutrients is of relevance. Furthermore you will get information about the

energy required by the human body including the basal metabolic rate as well as the

energy required in case of illness. The chapter closes explaining the different

methods of feeding that might be applied in case of illness. It is to be distinguished

between enteral and parenteral nutrition.


" Knowledge of the most important function of nutrients

" Description of both, mechanism and function of

gluconeogenesis

" Knowledge of the difference between essential and

conditionally essential nutrients

" Knowledge of the standard energy requirement as well

as of energy required in case of illness

" Explanation of the terms „enteral nutrition“ and

„parenteral nutrition“


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5.1 Nutrient Groups

Nutrients may be divided into two major groups i. e. calorific and non-calorificnutrients. The division of these two major groups of nutrition is based upon the fact

that non-calorific nutrients do not provide the body with the necessary substances for

energy production which, among other tasks (as described below), is ensured by high

calorie nutrients.

Non-calorific nutrients are water, electrolytes, vitamins and trace elements.

! Water is the biological „solvent“ in which all biochemical processes take place.

! Electrolytes (sodium, potassium, calcium, magnesium, chloride, phosphate and

bicarbonate) ensure the correct division of the fluid spaces and maintenance of

the correct conditions that are necessary to perform important tasks such as the

transmission of stimuli as well as muscle movements. Apart from that electrolytes

contribute to the formation of bones and teeth.

! Vitamines (A, D, E, K, B1, B2, B6, B12, C, biotin, folic acid, nicotinic acid and

pantothenic acid) as well as trace elements (iron, copper, zinc, manganese,

selenium, molybdenum, chromium, iodine and fluorine) are mainly important asparts of enzymes. Enzymes are substances the human body needs to perform

certain biochemical processes that would not go without them.

Calorific nutrients are proteins, carbohydrates and lipids:

! Proteins are substances consisting of up to 20 different building blocks, the so-

called amino acids. They are the only substances of the body containing aconsiderable quantity of the element nitrogen, i. e. 16 % of their dry weight. The

body produces its own proteins out of amino acids in order to ensure a variety of

different functions. In terms of quantity the development of muscles is of prior

importance since they provide the ability to perform physical work. Proteins that

are solved in fluid spaces as well as in blood are in second place as regards

quantity since they ensure defence reactions against infections, the binding and

transport of water-insoluble substances as well as blood coagulation in case of

injuries, just to name a few.


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Important Proteins are the functional mass of the body. All bodilyfunctions are based upon specialised and body-produced

proteins. They are chemically characterised by their 16 %

share of the element nitrogen.

Protein metabolism and synthesis are a constant process in the human body.

Amino acids that are produced as a result of protein metabolism are largely

reused for protein synthesis. Some, however, get lost during the oxidation

process, i. e. amino acids are transformed into the carbohydrate glucose (so-

called gluconeogenesis) serving as energy source for oxidation processes. So,

proteins do also contain calories, in fact 4 kcal/g. The process of gluconeogenesis serves to ensure that those cells and organs that cannot make

use of an alternative energy source (see section „carbohydrates“) are sufficiently

supplied with glucose. Gluconeogenesis is increased in case of infections or

injuries (see chapter 5.4).

Those amino acids lost in the process of gluconeogenesis must be supplied to

the body in the form of food protein which is found in high concentrations in meat,

fish and eggs.

Important Gluconeogenesis is the production of glucose serving toensure the supply of brain and red blood cells with this energy

source.

!

By carbohydrates we understand a group of substances consisting of differentbuilding blocks, all of them having in common the chemical formula Cn(H2O)n. In

terms of quantity glucose is the most important building block. The main purpose

of carbohydrates is to supply energy (4 kcal/g). In food they are mainly found as

starch in cereal products or potatoes. Further important carbohydrates are cane

sugar (saccharose) and milk sugar (lactose). Cells are only able to oxidise

glucose. Other building blocks of carbohydrates such as for example fruit sugar

(fructose) are therefore at first transformed into glucose.


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Glucose is the only energy source all body cells make use of for energy

production. For the brain and the red blood cells it is the only energy source. In

view to their central importance the body must ensure a continuous supply withglucose. Therefore, after intake of carbohydrates as part of the food a certain

share of glucose is stored in the liver as glycogen. This glycogen means a

reserve of 200 g of glucose. In case of a lack of external administration a

constant energy supply of the brain and red blood cells is ensured for a period of

18 hours. The only additional source of glucose the human body has is the

protein (see above).

Important Glucose is the only energy source for the brain and bloodcells. In case of a lack of external administration the human

body makes use of two mechanisms in order to keep these

tissues supplied with energy: The conversion of glycogen into

glucose and the conversion of amino acids into glucose

(gluconeogenesis).

! Among the lipids triglycerides mainly serve as energy source. Triglycerides

consist of glycerol and fatty acids, the latter being of importance for the synthesis

of membranes. Triglycerides also serve as the major medium for energy storage

in the body. Triglycerides mainly occur in oils and fats as well as in the fatty tissue

of meat. Oxidation of 1 g of triglycerides produces an average of 9 kcal.

Table 5 gives a survey on the calorific values of calorific nutrients

Table 5: Average calorific value of important nutrients per gram

1 g Carbohydrate 4 kcal 17 KJ

1 g Protein 4 kcal 17 KJ

1 g Fat 9 kcal 40 KJ


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5.2 Essential and Conditionally Essential Nutrients

Since the body has to sustain a natural loss of all nutrients, these losses need to be

compensated. In view to this fact the following questions arise:

1. To which extent may nutrients be interchanged against one another?

2. When does the reduced intake of a single nutrient lead to a deficit?

3. What consequences does the deficit of a nutrient have?

Since the answers to these questions are rather complex and extensive only basic

information will be given.

Ad 1) Subst itut ion of nutrients:

In most cases nutrients cannot be substituted against one another. This is the case,

for example, in all non-calorific nutrients, in 8 out of the 20 amino acids as well as in

the nitrogen contained in proteins, where the body is either not able to produce these

substances itself or the quantity produced is so small that the natural losses cannot

be compensated. These nutrients are called essential.

While the absolute need of calories must be covered by administration, carbohydrate

calories may to a large extend be substituted by lipid calories and vice versa. The

triglycerides of certain lipids, however, do contain two essential fatty acids, the

linoleic acid and the α-linolenic acid. Their functions in the membranes cannot be

replaced by any other nutrient.

Important The majority of nutrients is essential which means, the bodyneeds the substance for functioning. However, it is not in a

position to produce the substance at all or the quantity

produced is only insufficient.

Ad 2) Development of def ic its :

Essential nutrients need to be supplied by the intake of food in order to avoid the

development of deficits. The development of deficits depends on the degree of

nutrient demand. So in normal life a severe deficit in water develops after a period of

a few days already while a protein deficit is the result of a several weeks lasting lack


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of supply. In case of illness, a nutrient deficit can develop much more quickly. So, a

severe diarrhoea, for example, might lead to a serious water deficit within a few

hours‘ time and the considerably increased gluconeogenesis going along with

infections makes severe protein deficits occur after a few days already.

Ad 3) Consequences resul ting from def ic its

If a deficit of certain nutrients occurs, their tasks are ensured to a limited degree only

and finally are no longer fulfilled at all. This leads to the development of diseases that

may be treated by supplying the respective nutrient. An increase in deficit goes along

with a progression of the disease, increased disturbance of the bodily functions and

finally death from nutrient deficit.

Important Nutrient deficits lead to severe illness that might result indeficit-related death

Apart from essential nutrients there is the group of so-called conditionally essential

nutrients. In concrete terms, as regards their function these nutrients may not be

substituted by other nutrients. The healthy adult, however, does not really need tosupply them by way of food intake, since the body is able to produce them itself. In

elder or ill patients the demand of conditionally essential nutrients may be increased

or the endogenous production reduced which leads to a nutrient deficit. 12 out of 20

amino acids, for example, are not essential for the healthy adult while none of the 12

amino acids‘ functions may be compensated by another amino acid. Thus, a deficit of

such an amino acid will lead to the same consequences as it is the case for essential

nutrients (see above). Infants are a typical example, since almost all 20 amino acids

are essential.

Important Any nutrient getting into a deficit becomes essential, if itsfunction cannot be ensured by a substitute nutrient

For most of the nutrients there exist valuable recommendations for an adequate and

well-balanced food intake in healthy people, e. g. recommendations issued by the„Deutsche Gesellschaft für Ernährung“.


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5.3 Human Energy Requirements

The human energy requirements mainly depend on age, sex, height and weight as

well as of the degree of physical activity.

Apart from the need resulting from physical activity there is a minimum of energy a

person needs during the state of rest, the so-called basal metabolic rate. Depending

on the person’s constitution it amounts to 1110 – 1800 kcal/day for an adult ,

however, it may vary in very small or very tall persons. There are different

possibilities to determine the basal metabolic rate, such as tables giving standard

basal metabolic rates depending on age, sex and height. Apart from that the

empirical formulas acc. to Harris and Benedict have proven their usefulness:

BMR male = 66 + (13.5 x BW) + (5 x H) – (6.8 x A)

BMR female = 655 + (9.6 x BW) + (1.8 x H) – 4.7 x A)

Fig. 8: Formula to determine the basal metabolic rate acc. to Harris & Benedict

BMR = basal metabolic rate, BW = body weight in kg, H = height in cm, A = age

The basal metabolic rate is ensured by the body’s utilisation of calorie-containing

nutrients. Proteins, carbohydrates and lipids contribute their respective share in this

process depending on the amount of intake respectively. In Europe the usual

nutrition consists of 10 – 20 % proteins, 40 – 60 % carbohydrates and 20 – 40 %

lipids, the total always amounting to 100 %, of course.

The relative share of calorie-containing nutrients in energy production corresponds to

their amount of intake. However, excessive intake of lipids leads to a storage of lipids

in the adipose tissue. Furthermore, excess quantities of carbohydrates resulting from

excessive intake are also transformed into lipids which is finally stored in the adipose

tissue.

In healthy subjects a calorie demand exceeding the basal metabolic rate is mainly

due to an increase in physical activity.


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Important Energy requirements are defined as the amount of energythe body needs depending on the situation. It is made out

by the basic metabolic rate and possible additional

requirements resulting from physical work.

5.4 Energy Requirements in Case of Disease

A disease may cause a substantial increase of energy demand at rest. This is a

disease-induced increase of basal metabolic rate.

In clinical practise the energy requirement of an adult is simply determined as

25 kcal/kg body weight per day. In case of acute infections and inflammation or

severe injuries this value may increase to about 30 kcal/kg body weight per day. In

very rare cases such as severe burns it may be even increased to 35 – 40 kcal/kg

body weight per day.

Situations as described are characterised by a strongly increased consumption of

proteins. It may amount to four times the standard value and is due to a strong

increase of the gluconeogenesis. Since proteins represent the body’s functionalmass a severe, even life-threatening protein deficiency may develop.

Important Infections, inflammations and injuries go along with anincrease in energy demand. The body’s proper

functioning is critically at risk because of the protein

catabolism which is due to the considerably increased

gluconeogenesis.

5.5 Enteral and Parenteral Nutri tion

In clinical practise there may be situations where normal food intake by eating and

drinking is not possible. In case the intestine may be used as access, patients may

receive special diets by way of feeding tubes. This is called enteral nutrition

(enteros: greek for intestine). If enteral nutrition is not possible feeding is done via theveins, the method being called parenteral nutrition (passing the intestine). Both,


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enteral and parenteral nutrition serve to supply the body with a sufficient quantity of

nutrients in order to maintain the body’s function. However, particular with regard to

maximum protein supply deficits can often not be completely compensated.

Important If diseases make normal food intake impossible feedinghas to be done via tubes (enteral nutrition) or via the

veins (parenteral nutrition) since otherwise life-

threatening nutrient deficits may develop. In this respect a

protein deficit represents a particu lar risk.

Nutrient supply in enteral nutrition is mainly standardised by using tube feedings. As

regards composition and quantity of the respective single components these tube

feedings meet international dietetic demands.

Nutrient supply in enteral nutrition is done in accordance with a special diet regimen

consisting of suitable individual components such as

! Amino acid solutions

! Glucose solutions

! Lipid emulsions

! Electrolyte concentrates

! Vitamins and trace element preparations

Sooner or later all nutrients develop into a deficit if they are not adequately supplied.

Since such a deficit entails severe consequences, it must be ensured that inparenteral nutrition all nutrients are supplied in sufficient large quantities.

As regards nutrient supply in different clinical situations scientific literature provides a

number of useful recommendations (e. g. Safe Practices for Parenteral Nutrition

Formulations, JPEN 22 (1998) 49 – 66).


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5.6 Summary

Nutrients may be divided into two large groups: Among the non-calorific nutrients are

water, electrolytes, vitamins and trace elements while proteins, carbohydrates and

lipids belong to the group of calorific nutrients. The single nutrients contribute their individual shares to maintain the body’s function.

The majority of nutrients is essential, i. e. the body is in absolute need of them,

however, it cannot produce them itself (either at all or in sufficiently large quantities).

Talking of conditionally essential nutrients, we mean those nutrients, which the

human body is actually able to produce in sufficient quantities. However certain

circumstances may cause these nutrients to develop into a deficit.

The basal metabolic rate of humans depends on age, sex, body height and

weight. In addition, energy demand is influenced by the degree of physical activity.

The relative share of energy-containing nutrients in the body’s energy production

corresponds to the amount of them being supplied.

Illness may lead to a (significant) increase of energy demand. In case of severe

injuries, such as burns, the metabolism of proteins is significantly increased due the

process of gluconeogenesis which may result in a life-threatening protein deficiency.

Enteral nutrition (by way of tubes into the intestine) as well as parenteral nutrition (byway of catheters into the veins) are supplied in order to ensure sufficient intake of all

nutrients and thus maintenance of the body’s function.


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! Name the four non-calorific nutrient classes and explain their function for thebody!

! Explain the great importance of glucose!

! What function do triglycerides have?

! How many kcal of energy are respectively produced during metabolisation of

glucose, proteins and fat?

! Explain the process of gluconeogenesis, its purpose as well as the resulting

consequences in parenteral nutrition of severely injured patients!

! Explain the difference between essential and conditionally essential nutrients!

! What is to be understood by enteral and parenteral nutrition?

! On which factors does the human energy demand depend?

! What is the simplified formula to be applied for determining the energy demand in

enteral and parenteral nutrition?

! What consequences do acute infections and inflammations or severe injuries

have with regard to energy consumption?

! What individual components does a regimen for parenteral nutrition consist of?


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II

FUNDAMENTAL ELEMENTSOF INFUSION THERAPY

The second section of these lecture notes will provide information about the

fundamental elements of infusion therapy. Let us look at the standard definition of

“infusion”:

DefinitionInfusion (lat. Infundere, infusus):

The introduction of liquids into the body in a process that

circumvents the gastro-intestinal tract. Usually the liquid

is introduced into a vein (intravenous), less often an

artery, the subcutaneous adipose tissue (earlier

customary as a subcutaneous saline infusion)

Infusion thus means the introduction of liquid into the body – venously, arterially or

subcutaneously. The medical indication determines which substances must be

administered to the body. Infusion therapy deals with the question: ”How can I bring

this substance/solution (optimally) into the body?”

To answer this question, knowledge of various factors is required which are dealt with

in the section “Infusion Therapy” of these lecture notes.

To begin with, various infusion containers will be presented which have different

advantages and disadvantages depending on their respective characteristics. The

chapter dealing with infusion solutions then gives an overview of the treatment fields

in which infusion therapy is used and in the process indicates the most importantsolutions for the different application fields. A chapter on infusion technology follows


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which systematically presents the different application possibilities. In the final

chapter, you receive information concerning the dosage of the infusion quantities and

learn about the function of the various kinds of infusion equipment which have a

considerable influence on the exactitude of the dosage.


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6

THE INFUSION

CONTAINERSIn the following chapter, the advantages and disadvantages of different infusion

containers are explained and the special features of the containers are identified.

Infusion containers may be distinguished on the basis of characteristics such as their

area of application, transparency, sturdiness, weight, sterility, user-friendliness,

environmental impact, etc.

6.1 The Glass Bottle

In earlier times, glass bottles were the standard container; today they are increasingly

being superseded by plastic containers or bags. On the basis of their advantages,

however, glass bottles are still the container of choice for special solutions and

applications.

The glass bottle features various advantages . It is:

# transparent - this criterion is particularly important for the detection of

particles (there are also coloured bottles for light-sensitive contents).

# gas-proof and chemically inert - i.e. it does not react chemically with the

contents and is thus suitable for all types of infusion solutions.

#always the same size and therefore it is easy to calculate quantities,because the graduation does not shift as the bottle empties.


" Gain an overview of the various infusion containers

" Ability to cite the most important advantages and

disadvantages of the various infusion containers as well

as their areas of application


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The advantages of the glass bottle are, however, countered by various

disadvantages. The glass bottle:

$ is breakable.

$ has a considerable weight.

$ must be vented - this requires monitoring at the end of the infusion to

prevent a possible air embolism.

$ cannot support a pressure infusion using a pressure cuff.

$ has a piercing site which is not per se sterile and must therefore be

disinfected.

$ entails the risk of considerable particle contamination.

Note: In the hospital, reuse of glass bottles is only possiblewhen they contain the same solution and when a certain

type of glass is used. Recycling can only be done via the

usual public possibilit ies (glass disposal).

6.2 Infusion bags

In Germany, infusion bags are not frequently used. In other countries, however, they

are widely used and in some areas they are the predominant infusion container. To

avoid perforations, a special bag piercing spike is necessary.

Low weight, low costs and a range of application advantages have made bags

popular particularly with standard solutions. Infusion bags feature the following

advantages:

# They are user-friendly, i.e. it is not possible for the infusion system and inparticular the drop chamber to run empty because the bag collapses and at


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the end of the infusion there is an automatic stop of the fluid column thus

making it a closed system which in turn makes an air embolism impossible.

# The infusion sets functions without venting.

# It is easy to mix the contents when admixtures are made.

# They are flexible (important for pressure infusions).

# They are transparent (important for detecting possible precipitations).

# They are easy to use for a pressure infusion.

6.2.1 BAGS MADE OF PVC

Bags also have considerable disadvantages, if made from PVC for example:

$ High particle contamination.

$ High content of plasticisers.

$ A high gas permeability - therefore not suitable for all solutions (danger of

oxidation). As storage time and temperature increase there is substantial

water evaporation.

$ There are environmental problems regarding the disposal of PVC.

Incineration, for example, produced hydrochloric acids.

$ Extreme absorption of many drugs.

6.2.2 ECOBAG® C.E. AND ECOBAG® I.V. – BAGS FROM B|BRAUNB|BRAUNB|BRAUNB|BRAUNThe Ecobag® consists of a composite film made of polyethylene (PE) and

polypropylene (PP). It has got three significant advantages:


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# It has a low particle contamination.

# The disposal of the Ecobag bags is environmentally harmless; wastevolume is small and in contrast to PVC-bags no hydrochloric acid and dioxins

are produced during incineration.

# The material does not adsorb drugs.

6.2.3 THE MIXING BAG (NUTRIMIX® FROM B|BRAUNB|BRAUNB|BRAUNB|BRAUN)

The mixing bag is used for preparing mixed infusions during total parenteral nutrition

(TPN). It has got the following advantages:

# Adjustment to the patient is possible: Nutrition solutions for a whole day’s

requirements (2 -3 l) can be prepared in this bag for the special needs of the

patient.

# Reduced work: The construction of large infusion regimens (administration

via numerous different containers) is not necessary.

# No incompatibility: The danger of an incompatibility during infusion does

not exist.

# Low particle contamination: Particle contamination – in contrast to large

infusion regimens – is kept to a minimum.

# Transparency: The bag body is fully transparent.

# Low level of contaminants: The entire bag is free from PVC and

plasticisers.

Note: If lipid solutions are added, then the mixed solutioncannot be administered via an 0.2 µµµµm filter. A special

1.2 µµµµm lipid filter must be used.


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Nutriflex®, Nutriflex®Lipid fromB|BRAUNB|BRAUNB|BRAUNB|BRAUN

These products are pre-filled (ready to use) mixing bags for parenteral nutrition

(PVC-free).

6.3 Plastic Bottles: Polyethylene Bott les

Particularly in Germany, plastic bottles are very widely used because they represent

a good combination of the advantages of the traditional glass bottle and the plastic

bag. The application fields are similar to those of plastic bags:

6.3.1 PLASCO

The Plasco® is no longer produced by B|BRAUN. Because this product is still sold

by other companies, its advantages and disadvantages are presented here to assess

its fields of application.

Plasco® has got the following advantages:

# Low particle contamination in contrast to glass bottles and PVC bags.

# Lower water evaporation in contrast to PVC bags.

# Low weight: Plasco® is only half the weight of a glass bottle.

# Unbreakable.

# Environmentally harmless: Plasco® does not contain any plasticisers and

is recyclable. Even when incinerated the only by-products are CO2 and H20.

The Plasco® also has the following disadvantages:

$ Venting of the system is necessary for complete emptying (the bottle

collapses slowly).

$ Clouding: Plastic bottles have a slight clouding effect as a result of the

material.

$ Exact fluid balancing is not possible without venting and with a collapsed

bottle.

$ Larger amount of air in the container.


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6.3.2 ECOFLAC® PLUS from B|BRAUNB|BRAUNB|BRAUNB|BRAUN

The Ecoflac® Plus has got the following advantages:

# Unbreakable.

# No venting necessary.

# Good handling, s table.

# Polyethylene is suitable for nearly all solutions.

# Low particle contamination.

# Space for the admixture of additional drugs.

# Low waste quantities, low weight.

# Recyclable.

A disadvantage is the low accuracy of the scale, making fluid balance difficult.

6.3.3 MINI-PLASCO

The B|BRAUN company has launched the Mini-Plasco® as an alternative to injection

ampoules. In the sizes 5, 10 and 20 ml, they serve as a replacement for glass

ampoules and have got the following advantages:

# Free-standing.

# Even open containers that fall over do not run out

# Opening without filing, that means without splinters and the danger of

injury.

# Simple, problem-free disposal (see Plasco® bottle)


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Note: Glass bottles, plastic bottles, Ecobag® as well as mixingbags (NUTRIMIX®) are all being used with normal infusion

sets (sharp, pointed and long piercing spikes). For the

use of other infusion bags and for blood t ransfusion bags

only the special bag infusion sets should be used

because of the danger of perforation (For information

about infusion sets, see

Chapter 9).

6.4 Summary

Glass bottles, infusion bags and plastic bottles are available as infusion

containers. Infusion containers differ in regard to characteristics such as

transparency, robustness, weight, sterility, user-friendliness, environmental

characteristics, etc. Because of their different advantages and disadvantages, the

different infusion containers are suitable for different areas of application.

Glass bottles, plastic bottles, Ecobag® ,mixing bags (NUTRIMIX®) and ready-to-use

systems such as Nutriflex® and NuTRIflex® Lipid are used with normal infusion sets(sharp, pointed and long piercing spikes). For the use of other infusion bags and for

blood transfusion bags only the special bag infusion sets should be used because of

the danger of perforation.


!

In what ways are the various infusion containers different from each other?

! List some of the important advantages and disadvantages of glass bottles,

infusion bags and plastic bottles.

! What is to be observed when adding lipid solutions using in mixing bags?

! Which kinds of infusion sets are to be used with the different infusion containers?

! Why does venting of infusion containers play an important role?

! What effect does the choice of the container have on the choice of the infusion

set?


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7

THE INFUSION SOLUTIONS

All substances which are supplied externally that shall have an effect inside the body

(i. e. not on the body’s surfaces) need to enter the blood circulation. Distribution from

there to other fluid spaces or absorption by body cells mainly depends on the

purpose the substance has got for the body. So, for example, oxygen enters bloodcirculation via the membranes of the lung tissue and is distributed from there into the

body cells. Nutrients enter the blood circulation via the membranes of the intestine

and in most cases they are distributed from there into the cells. There are, however,

a few exceptions, such as the electrolyte ions sodium and chloride that are hardly

absorbed by the cells and therefore remain in the fluid outside the cells, the so-called

extracellular space.

Drugs that shall have an effect inside the body also need to enter the blood

circulation first. They enter the blood circulation via the membranes of the lung, the

intestine or possibly the mucous membrane. The way drugs enter the blood

circulation are not the same for all drugs.

Generally speaking, for intake of nutrients as well as of drugs, entrance into the blood

circulation takes place via the intestine. There are situations, however, where the

intestine does not function (e. g. after major surgery of the intestine) or may not be

used (e. g. preparation for surgery of the gastro-intestinal tract). Finally, there are

substances such as insulin, for example, where the blood circulation is generally notentered via the intestine. In those cases the substance needs to be dissolved in

water or a fat emulsion and is supplied by injection into then skin (subcutaneously),


Knowledge of the different fluid spaces in the body and

their respective interactions.

Comprehension of the decisive influence of the sodiumconcentration on the distribution of the infusion solutions

to the fluid spaces

Knowledge of the most important infusion solutions and

their areas of application

Knowledge of the standard infusion filters


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into the muscles (intramuscularly) or into the veins (intravenously). All methods of

administration circumvent the intestine and are therefore termed „ parenteral“

(Greek: for by-passing the intestine).

With regard to preparation it is to be distinguished between solutions/emulsions for injection and solutions/emulsions for infusion. The amount to be administered is the

decisive criteria for classification

! Solutions/emulsions for injection: ≤ 100 ml

! Solutions/emulsions for infusion ≥ 100 ml

The criteria of distinction for 100 ml containers is the configuration of the piercing

spike of an infusion set which does not fit for an injection container (see chapter 9.1).

Usually injection is done by help of an injection needle or a syringe into the muscular

tissue, sometimes injection is done into the skin or into a vein. The duration of

application is relatively short (between a few seconds and several minutes).

In infusions administration is always done via a vein. Apart from acute situations an

infusion lasts for a period of hours. Certain cases may require patients to be infused

for days and even weeks. Containers that have run empty will then be replaced by

new ones. Thus, the purpose of an infusion is to supply substances and fluids inlarge quantities and usually for a longer period of time.

This chapter deals with the most important types of infusion solutions/emulsions

including their areas of application. It provides the physiological principles (physical

and chemical processes) necessary to comprehend the composition of infusion

solutions.

Important Infusion solutions are large-quantity preparations of substances which are dissolved in water or lipid

emulsions being supplied via the veins.


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7.1 Fundamental Physiology of the Fluid Spaces

7.1.1 THE FLUID SPACES

Inside the body the cells are separated by membranes. The fluid space inside these

cells is called intracellular space. This space is characterised by an electrolyte

profile being rich in potassium, magnesium and phosphate while sodium, calcium

and chloride are hardly present.

All cells are surrounded by a fluid, the fluid space being called interstitial space. The

circulatory system is a further fluid space, called intravascular space partly being in

contact with the interstitial space via membranes. With regard to their electrolyte

profile the interstitial and the intravascular space are almost identical (see tab. 6).

Compared with the intravascular space the fluids in these two spaces are relatively

rich in sodium, calcium and chloride while the content of potassium, magnesium and

phosphate is relatively low. The total of interstitial and intravascular space is termed

extracellular space.

Table 6: Concentration of selected electrolytes in different fluid spaces

Intracellular space Extracellular space

Intersitial space Intravascular space

Sodium 10 mmol/l 143 mmol/l 141 mmol/l

Potassium 155 mmol/l 4 mmol/l 4 mmol/l

Calcium < 0.001 mmol/l 1.3 mmol/l 2.5 mmol/l

Magnesium 15 mmol/l 0.7 mmol/l 1 mmol/l

Chloride 8 mmol/l 115 mmol/l 103 mmol/l

Phosphate 65 mmol/l 1 mmol/l 1 mmol/l

Important Sodium is the predominant cation in the extracellular flu id


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7.1.2 EXCHANGE PROCESSES BETWEEN THE FLUID SPACES

There is a constant process of exchange between the above fluid spaces. This

entails surmounting of barriers since the degree of the membranes‘ permeability isnot the same for all substances. Processes of exchange have to take place through

the membranes and there exists a large number of different possibilities.

The easiest method of exchange is the substances passing the pores of the

membrane without being hindered. The pores‘ diameter is much larger than the

diameter of the substances they shall let pass. The pores of the membranes

surrounding the intravascular and the interstitial space are so large, that substances

such as electrolytes, amino acids and glucose may easily pass while large molecules(so-called macro-molecules) such as plasma proteins hardly pass. Since plasma

proteins retain water, exchange of the above products may take place between the

interstitial and the intravascular space without the level of fluid in the intravascular

infusion therapy complete

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