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Organization of the Body: Control of the Internal Environment
BASIC SCIENCE
Interactions between water molecules
Organization of the Body: Control of the Internal Environment
Hδ+ Hδ+
Iain Campbell
Hδ+ Oδ–
Oδ–
Hδ+
Hδ+ Hδ+
Oδ–
The mammalian cell comprises 70% water, 15% protein, 7% nucleic acids, 2% carbohydrate, 2% lipid, 1% inorganic ions and 3% other small molecules. The predominant substance, water, is made up of two atoms of hydrogen and one of oxygen and is described as ‘polar’. A polar molecule has an overall charge, or an uneven distribution of charge on its surface. The most polar of small particles are ions (e.g. Na+, K+) which have lost an electron from their outer shell. However, even covalently bound molecules (e.g. water) demonstrate polarity by virtue of the uneven distribution of their electron ‘cloud’. In water, the oxygen atom pulls electrons towards itself so the electron cloud is more dense over that part of the molecule, which is thus relatively more negative than it is over the hydrogen atoms. The partial negative charge over the oxygen atom is attracted to the partial positive charge over the neighbouring hydrogen atoms, and this weak ‘hydrogen bonding’ keeps the molecules together (Figure 1) and gives water its principal characteristic (i.e. a liquid, which, for the size of its molecule, has a relatively high boiling point). The polarity of water contrasts with that of organic molecules, made up entirely of carbon and hydrogen ions (e.g. methane) which are non-polar. The carbon–hydrogen bonds lead to an even distribution of electrons so that the molecules do not interact with each other. Polar and non-polar compounds do not mix well; the water molecules bond together and exclude the nonpolar substances, which may pack together because of their lack of interaction. There is some attraction between non-polar compounds, however, as a result of random variations in the density of the electron cloud, which results in minor transient degrees of polarity inducing opposite charges in neighbouring molecules and transient attractions between them; these are known as van der Waal forces. Their effects are small compared with the exclusion by water. The state of polarity results from the fact that, compared with hydrogen, certain atoms are always electronegative. Biochemically, the important polar atoms are oxygen, phosphorus and nitrogen along with certain functional groups based on these atoms: the hydroxyl group (OH), the amino group (NH2) and the orthophosphate group (OPO3). Thus polar compounds, such as
Hδ+
Hδ+
Owing to the polarity of the water molecule (i.e. an uneven distribution of negative and positive charge) hydrogen bonding occurs between neighbouring molecules. This bonding is weak and bonds are constantly being formed and broken, but it accounts for the fact that water is a liquid whereas larger nonpolar molecules such as methane and carbon dioxide are gases 1
glucose (with a large number of OH groups), lactic acid (with a COO group) and other small metabolites, including most amino acids, form hydrogen bonds and are water-soluble. Molecules that have both polar and non-polar regions, are partly soluble and partly insoluble in water and are described as ‘amphipathic’. Amphipathic molecules submersed in an aqueous environment generally take up one of two configurations. • As micelles they form spherical droplets with their polar heads facing outwards and their hydrophobic tails together in the centre. • As bilayered sheets or membrane, their water-soluble heads are in the aqueous environment and their hydrophobic tails form the substance of the membrane. An example of this is the phospholipids that make up cell membranes (Figure 2). Cell membranes comprise two layers of these compounds, with the water-soluble polar phosphate head presented to the aqueous environment and the two layers of hydrophobic non-polar hydrocarbon lipid tails making up the body of the membrane. Molecules passing through such membranes have to traverse both the hydrophilic regions (comprising the polar phosphate heads of the phospholipid molecules) and the thickness of the hydrophobic interior (comprising the hydrocarbon chains of the fatty acids). Specific carrier proteins are embedded in the body of the membrane to facilitate these processes. In general, hydrophobic lipid-soluble substances traverse membranes more easily than their polar water-soluble counterparts.
Body water volumes
Iain Campbell is Reader in Anaesthesia at the University of Manchester and Honorary Consultant Anaesthetist at the University Hospitals of South Manchester, UK. He qualified from Guy’s Hospital Medical School, London, UK, and trained in anaesthesia in Zimbabwe, Southend, Leeds, UK, and Montreal, Canada. His research interests include the metabolic aspects of critical illness and exercise.
SURGERY
Hδ+ Oδ–
Hδ+
Polar and non-polar molecules
Oδ–
In the young adult male, 60% of the body is water; 40% intracellular fluid (ICF) and 20% extracellular fluid (ECF). Of the ECF, 5% is intravascular and 15% extravascular or interstitial (i.e. between the cells). The composition of the ECF resembles that of sea water, but is more dilute.
56a ii
© 2003 The Medicine Publishing Company Ltd
BASIC SCIENCE
������������������������������������
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CH3 CH3
N
CH3
�������������������
Choline
CH2
�������
������
CH2 O
H
O
O
P
H
H
O
C
C
C
O
O
H
C
CH2
O
O
Phosphate
CH2
���������� ��
C
�������� ���
��������������� ��� ���� �� � ��� ��������� ��������� ��� ��� ������������
Fatty acids
CH2 CH2
CH2 CH2
CH2 CH2
Nonpolar tail Polar head
Non-polar tail
CH3
��� ��� ������������
are tritiated or deuterated water, sodium bromide is used for ECF volume, and Evans’ blue dye, labelled albumin, or red blood cells, with appropriate corrections made for haematocrit, are used for plasma. Plasma is normally 93% water. ICF volume is calculated from the difference between total body water and ECF volume. The interstitial ECF bathes the outside of the cells and provides their immediate environment. The intravascular ECF provides the transport system for nutrients and waste products. The ECF is ultimately a medium of exchange between the cells and the external environment. Its principal cation is sodium. Interstitial ECF normally contains little or no protein. Other types of ECF, in addition to plasma, include lymph and CSF and transcellular fluid (e.g. eye humours). ECF makes up the immediate environment of the cells and its nature and composition is tightly controlled. In contrast, the ICF is rich in potassium and poor in sodium. It contains protoplasm, a complex mixture of substances that includes most of the protein in the body and which shows the features of life: • organization into specific structural units • ability to enter into chemical activities that include the transformation of energy and the maintenance or synthesis of the protoplasm itself • ability to respond to changes in the environment • ability to grow and reproduce.
CH2
CH2 CH2
Palmitic acid
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3
CH2
CH2
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CH CH
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���
CH2
CH2
�������
Non-polar tail
CH2
CH2
CH2 CH3
Stearic acid 2
The volumes of the various fluid compartments can be measured using dilutional techniques (Figure 3). A known amount of tracer, which remains in the compartment being measured, is injected or ingested. The volume of dilution (V) can be calculated from the total amount injected (M), from its final dilution in the compartment into which it is injected (m/unit volume) less the amount excreted (E) over the time it takes for mixing to occur: V= M-E/m. The tracers commonly used for total body water measurement
SURGERY
����� ���
��������
CH2
CH2
��� ���� �
Polar head
CH2
CH2
�������
��������
CH2
CH2
������
�������
Glycerol
CH2
CH2
�������
H
CH2
CH2
Very polar head
�������������������
56b iii
© 2003 The Medicine Publishing Company Ltd
BASIC SCIENCE
Tissues, organs and organ systems
Organization of the body from cells to organ systems
Cells are units of protoplasm bounded by phospholipid membranes formed by the interaction of hydrophobic and hydrophilic molecules. Life as a single-celled organism is obviously vulnerable to the vicissitudes of the environment. It is directly exposed to the external world and does not have the physiological resources to protect itself. In multicellular organisms, the cells have differentiated to perform different functions and have taken on different roles such as movement, digestion and reproduction. When groups of cells are closely associated functionally they form a tissue of which there are four types. Epithelial tissue – this comprises close-packed sheets of cells that cover the body surfaces and line the various cavities, tubes and hollow viscera. Apart from its structural role, epithelium may also secrete, absorb and filter. Connective tissue – this is the most widely distributed tissue in the body. Its cells are loosely arranged and separated by intercellular matrix, which contains fibres, soluble protein and crystalline complexes. It supports and partitions nearly all components of the body and its rearrangement determines growth. Connective tissue includes bone, cartilage, ligaments, blood and adipose tissue. Muscle – there are three types of muscle. Skeletal muscle enables the body to move and react to external stimuli. Smooth muscle, in part, forms the walls of the gastrointestinal tract, the blood vessels and other hollow viscera (e.g. bladder, uterus). Cardiac muscle pumps blood round the cardiovascular system. Nervous tissue – this constitutes the central (brain and spinal cord) and peripheral nervous systems (somatic and autonomic). Neurons are associated with glial tissue, which provides them with structural and metabolic support. Tissues form organs and a variety of tissues may contribute to the formation of one organ (Figure 4). The gastrointestinal tract and cardiovascular systems, for example, are made of muscle lined by epithelium. The epithelium of the gastrointestinal tract secretes digestive juices and absorbs nutrients, and is under central (autonomic) nervous control with neural networks within the wall of the gut. Organs that share in the performance of related tasks are grouped into systems. These are classified as the cardiovascular, respiratory, gastrointestinal, nervous, locomotor, genitourinary and reticuloendothelial systems.
Pluripotential cell
Cell differentiation Muscle
Connective Epithelial tissue tissue
Tissues
Organs (e.g. heart, liver, kidneys)
Organ systems (e.g. gastrointestinal, respiratory, cardiovascular)
4
cell and the ECF. To function properly, each protein has its own particular configuration or shape, which is a function of pH, temperature and ionic concentration. When conditions move outside of a relatively narrow range, protein configuration is altered and the ability to function properly is diminished or may be lost. Homeostatic mechanisms maintain the stability of the internal environment. They operate principally through the endocrine and nervous systems. Control systems possess sensors to monitor variables and effectors to enable a response to alterations in that variable. The desired range of any variable is set, usually in the CNS, and any movement outside that range activates mechanisms that bring the variable back within range. For example, a rise in body temperature brought about by exercise results in peripheral vasodilatation and, depending on the severity of the exercise, sweating. This produces increased heat loss and a tendency for body temperature to return to normal. Most control systems are of the negative feedback type and work to restore the variable to the normal value. Some, however, incorporate positive feedback and these tend to destabilize. An example of this is seen when a rise in body temperature increases metabolic rate and thus heat production and raises body temperature further. Sensors are situated centrally, usually in the hypothalamus, but there are peripheral sensors such as those for PO2 and blood
Control of the internal environment: homeostasis For a living organism to function optimally, the internal environment (the composition of the ECF) has to be kept constant in terms of the PO2, PcO2, pH, osmotic pressure, temperature and concentrations of the various hormones, substrates, waste products and ions. Poikilotherms (e.g. reptiles) are unable to regulate their body temperature and are therefore sensitive to environmental conditions, but mammals maintain their body temperature in the face of wide variations in environmental temperatures and thus remain active under a variety of conditions. Outside these tightly controlled conditions, function is suboptimal. The molecular basis for this is in the configuration of proteins. Proteins form the structural components of cells, the enzymes that catalyse biochemical reactions and the receptors and channels in cell membranes that connect the inside of the
SURGERY
Nerve
iv 56c
© 2003 The Medicine Publishing Company Ltd
BASIC SCIENCE
pressure which are part of, and transmit their signals via, the autonomic nervous system. Stimuli that activate the endocrine system may also be detected in the CNS or by special cells in the periphery, such as those in the pancreas that detect changes in blood sugar. The mechanisms that correct homoeostatic disturbances may be endocrine or neural, but generally the two systems work together. u FURTHER READING Frayn K N. Metabolic Regulation. A Human Perspective. London: Portland Press, 1996. Gannong W F. Review of Medical Physiology. 19th edition. Stamford, Connecticut: Appleton and Lange, 1999. Pockock G, Richards C D. Human Physiology. The Basis of Medicine. Oxford: Oxford University Press, 1999.
SURGERY
56d v
© 2003 The Medicine Publishing Company Ltd
Interactions between water molecules
Organization of the Body: Control of the Internal Environment
Hδ+ Hδ+
Iain Campbell
Hδ+ Oδ–
Oδ–
Hδ+
Hδ+ Hδ+
Oδ–
The mammalian cell comprises 70% water, 15% protein, 7% nucleic acids, 2% carbohydrate, 2% lipid, 1% inorganic ions and 3% other small molecules. The predominant substance, water, is made up of two atoms of hydrogen and one of oxygen and is described as ‘polar’. A polar molecule has an overall charge, or an uneven distribution of charge on its surface. The most polar of small particles are ions (e.g. Na+, K+) which have lost an electron from their outer shell. However, even covalently bound molecules (e.g. water) demonstrate polarity by virtue of the uneven distribution of their electron ‘cloud’. In water, the oxygen atom pulls electrons towards itself so the electron cloud is more dense over that part of the molecule, which is thus relatively more negative than it is over the hydrogen atoms. The partial negative charge over the oxygen atom is attracted to the partial positive charge over the neighbouring hydrogen atoms, and this weak ‘hydrogen bonding’ keeps the molecules together (Figure 1) and gives water its principal characteristic (i.e. a liquid, which, for the size of its molecule, has a relatively high boiling point). The polarity of water contrasts with that of organic molecules, made up entirely of carbon and hydrogen ions (e.g. methane) which are non-polar. The carbon–hydrogen bonds lead to an even distribution of electrons so that the molecules do not interact with each other. Polar and non-polar compounds do not mix well; the water molecules bond together and exclude the nonpolar substances, which may pack together because of their lack of interaction. There is some attraction between non-polar compounds, however, as a result of random variations in the density of the electron cloud, which results in minor transient degrees of polarity inducing opposite charges in neighbouring molecules and transient attractions between them; these are known as van der Waal forces. Their effects are small compared with the exclusion by water. The state of polarity results from the fact that, compared with hydrogen, certain atoms are always electronegative. Biochemically, the important polar atoms are oxygen, phosphorus and nitrogen along with certain functional groups based on these atoms: the hydroxyl group (OH), the amino group (NH2) and the orthophosphate group (OPO3). Thus polar compounds, such as
Hδ+
Hδ+
Owing to the polarity of the water molecule (i.e. an uneven distribution of negative and positive charge) hydrogen bonding occurs between neighbouring molecules. This bonding is weak and bonds are constantly being formed and broken, but it accounts for the fact that water is a liquid whereas larger nonpolar molecules such as methane and carbon dioxide are gases 1
glucose (with a large number of OH groups), lactic acid (with a COO group) and other small metabolites, including most amino acids, form hydrogen bonds and are water-soluble. Molecules that have both polar and non-polar regions, are partly soluble and partly insoluble in water and are described as ‘amphipathic’. Amphipathic molecules submersed in an aqueous environment generally take up one of two configurations. • As micelles they form spherical droplets with their polar heads facing outwards and their hydrophobic tails together in the centre. • As bilayered sheets or membrane, their water-soluble heads are in the aqueous environment and their hydrophobic tails form the substance of the membrane. An example of this is the phospholipids that make up cell membranes (Figure 2). Cell membranes comprise two layers of these compounds, with the water-soluble polar phosphate head presented to the aqueous environment and the two layers of hydrophobic non-polar hydrocarbon lipid tails making up the body of the membrane. Molecules passing through such membranes have to traverse both the hydrophilic regions (comprising the polar phosphate heads of the phospholipid molecules) and the thickness of the hydrophobic interior (comprising the hydrocarbon chains of the fatty acids). Specific carrier proteins are embedded in the body of the membrane to facilitate these processes. In general, hydrophobic lipid-soluble substances traverse membranes more easily than their polar water-soluble counterparts.
Body water volumes
Iain Campbell is Reader in Anaesthesia at the University of Manchester and Honorary Consultant Anaesthetist at the University Hospitals of South Manchester, UK. He qualified from Guy’s Hospital Medical School, London, UK, and trained in anaesthesia in Zimbabwe, Southend, Leeds, UK, and Montreal, Canada. His research interests include the metabolic aspects of critical illness and exercise.
SURGERY
Hδ+ Oδ–
Hδ+
Polar and non-polar molecules
Oδ–
In the young adult male, 60% of the body is water; 40% intracellular fluid (ICF) and 20% extracellular fluid (ECF). Of the ECF, 5% is intravascular and 15% extravascular or interstitial (i.e. between the cells). The composition of the ECF resembles that of sea water, but is more dilute.
56a ii
© 2003 The Medicine Publishing Company Ltd
BASIC SCIENCE
������������������������������������
��������������������������������������������������������������� ��������������������������������������������������������� ��������������������
CH3 CH3
N
CH3
�������������������
Choline
CH2
�������
������
CH2 O
H
O
O
P
H
H
O
C
C
C
O
O
H
C
CH2
O
O
Phosphate
CH2
���������� ��
C
�������� ���
��������������� ��� ���� �� � ��� ��������� ��������� ��� ��� ������������
Fatty acids
CH2 CH2
CH2 CH2
CH2 CH2
Nonpolar tail Polar head
Non-polar tail
CH3
��� ��� ������������
are tritiated or deuterated water, sodium bromide is used for ECF volume, and Evans’ blue dye, labelled albumin, or red blood cells, with appropriate corrections made for haematocrit, are used for plasma. Plasma is normally 93% water. ICF volume is calculated from the difference between total body water and ECF volume. The interstitial ECF bathes the outside of the cells and provides their immediate environment. The intravascular ECF provides the transport system for nutrients and waste products. The ECF is ultimately a medium of exchange between the cells and the external environment. Its principal cation is sodium. Interstitial ECF normally contains little or no protein. Other types of ECF, in addition to plasma, include lymph and CSF and transcellular fluid (e.g. eye humours). ECF makes up the immediate environment of the cells and its nature and composition is tightly controlled. In contrast, the ICF is rich in potassium and poor in sodium. It contains protoplasm, a complex mixture of substances that includes most of the protein in the body and which shows the features of life: • organization into specific structural units • ability to enter into chemical activities that include the transformation of energy and the maintenance or synthesis of the protoplasm itself • ability to respond to changes in the environment • ability to grow and reproduce.
CH2
CH2 CH2
Palmitic acid
��������
3
CH2
CH2
�������
������������������������������������������������������������������������������ ����������������������������������������������������������������������������� ��������������������������������������������������������������������������� ������������������������������������������������������������
CH CH
���������� �� �������� �
���
CH2
CH2
�������
Non-polar tail
CH2
CH2
CH2 CH3
Stearic acid 2
The volumes of the various fluid compartments can be measured using dilutional techniques (Figure 3). A known amount of tracer, which remains in the compartment being measured, is injected or ingested. The volume of dilution (V) can be calculated from the total amount injected (M), from its final dilution in the compartment into which it is injected (m/unit volume) less the amount excreted (E) over the time it takes for mixing to occur: V= M-E/m. The tracers commonly used for total body water measurement
SURGERY
����� ���
��������
CH2
CH2
��� ���� �
Polar head
CH2
CH2
�������
��������
CH2
CH2
������
�������
Glycerol
CH2
CH2
�������
H
CH2
CH2
Very polar head
�������������������
56b iii
© 2003 The Medicine Publishing Company Ltd
BASIC SCIENCE
Tissues, organs and organ systems
Organization of the body from cells to organ systems
Cells are units of protoplasm bounded by phospholipid membranes formed by the interaction of hydrophobic and hydrophilic molecules. Life as a single-celled organism is obviously vulnerable to the vicissitudes of the environment. It is directly exposed to the external world and does not have the physiological resources to protect itself. In multicellular organisms, the cells have differentiated to perform different functions and have taken on different roles such as movement, digestion and reproduction. When groups of cells are closely associated functionally they form a tissue of which there are four types. Epithelial tissue – this comprises close-packed sheets of cells that cover the body surfaces and line the various cavities, tubes and hollow viscera. Apart from its structural role, epithelium may also secrete, absorb and filter. Connective tissue – this is the most widely distributed tissue in the body. Its cells are loosely arranged and separated by intercellular matrix, which contains fibres, soluble protein and crystalline complexes. It supports and partitions nearly all components of the body and its rearrangement determines growth. Connective tissue includes bone, cartilage, ligaments, blood and adipose tissue. Muscle – there are three types of muscle. Skeletal muscle enables the body to move and react to external stimuli. Smooth muscle, in part, forms the walls of the gastrointestinal tract, the blood vessels and other hollow viscera (e.g. bladder, uterus). Cardiac muscle pumps blood round the cardiovascular system. Nervous tissue – this constitutes the central (brain and spinal cord) and peripheral nervous systems (somatic and autonomic). Neurons are associated with glial tissue, which provides them with structural and metabolic support. Tissues form organs and a variety of tissues may contribute to the formation of one organ (Figure 4). The gastrointestinal tract and cardiovascular systems, for example, are made of muscle lined by epithelium. The epithelium of the gastrointestinal tract secretes digestive juices and absorbs nutrients, and is under central (autonomic) nervous control with neural networks within the wall of the gut. Organs that share in the performance of related tasks are grouped into systems. These are classified as the cardiovascular, respiratory, gastrointestinal, nervous, locomotor, genitourinary and reticuloendothelial systems.
Pluripotential cell
Cell differentiation Muscle
Connective Epithelial tissue tissue
Tissues
Organs (e.g. heart, liver, kidneys)
Organ systems (e.g. gastrointestinal, respiratory, cardiovascular)
4
cell and the ECF. To function properly, each protein has its own particular configuration or shape, which is a function of pH, temperature and ionic concentration. When conditions move outside of a relatively narrow range, protein configuration is altered and the ability to function properly is diminished or may be lost. Homeostatic mechanisms maintain the stability of the internal environment. They operate principally through the endocrine and nervous systems. Control systems possess sensors to monitor variables and effectors to enable a response to alterations in that variable. The desired range of any variable is set, usually in the CNS, and any movement outside that range activates mechanisms that bring the variable back within range. For example, a rise in body temperature brought about by exercise results in peripheral vasodilatation and, depending on the severity of the exercise, sweating. This produces increased heat loss and a tendency for body temperature to return to normal. Most control systems are of the negative feedback type and work to restore the variable to the normal value. Some, however, incorporate positive feedback and these tend to destabilize. An example of this is seen when a rise in body temperature increases metabolic rate and thus heat production and raises body temperature further. Sensors are situated centrally, usually in the hypothalamus, but there are peripheral sensors such as those for PO2 and blood
Control of the internal environment: homeostasis For a living organism to function optimally, the internal environment (the composition of the ECF) has to be kept constant in terms of the PO2, PcO2, pH, osmotic pressure, temperature and concentrations of the various hormones, substrates, waste products and ions. Poikilotherms (e.g. reptiles) are unable to regulate their body temperature and are therefore sensitive to environmental conditions, but mammals maintain their body temperature in the face of wide variations in environmental temperatures and thus remain active under a variety of conditions. Outside these tightly controlled conditions, function is suboptimal. The molecular basis for this is in the configuration of proteins. Proteins form the structural components of cells, the enzymes that catalyse biochemical reactions and the receptors and channels in cell membranes that connect the inside of the
SURGERY
Nerve
iv 56c
© 2003 The Medicine Publishing Company Ltd
BASIC SCIENCE
pressure which are part of, and transmit their signals via, the autonomic nervous system. Stimuli that activate the endocrine system may also be detected in the CNS or by special cells in the periphery, such as those in the pancreas that detect changes in blood sugar. The mechanisms that correct homoeostatic disturbances may be endocrine or neural, but generally the two systems work together. u FURTHER READING Frayn K N. Metabolic Regulation. A Human Perspective. London: Portland Press, 1996. Gannong W F. Review of Medical Physiology. 19th edition. Stamford, Connecticut: Appleton and Lange, 1999. Pockock G, Richards C D. Human Physiology. The Basis of Medicine. Oxford: Oxford University Press, 1999.
SURGERY
56d v
© 2003 The Medicine Publishing Company Ltd