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BSc Adult Nursing
NURS08046
Responding to Ill Health
Level 8
Life Science
Lecture Notes
Responding to Ill Health NURS08046 – Life Science Notes
Contents
pages
Introduction
2
Cardiovascular System
3
Endocrine System
12
Urinary System
18
Respiratory System
28
Cells
Pharmacology
`
35
43
Figures/diagrams are for illustrative purposes only and may include more or less detail than is found in
the text. All images used are taken from Wikicommons Media or other open source (details given) or
produced by UWS staff.
Front cover image:
US Department of Energy (2005) DNA split
https://commons.wikimedia.org/wiki/File:Dna-split.png
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Responding to Ill Health NURS08046 – Life Science Notes
Responding to Ill Health
NURS08046 - Level 8
Introduction
The aim of the life sciences component of this module is to build on the
anatomy and physiology delivered at level 7 to support learning related to
health and pathophysiology studied in year two modules. Life Science will be
taught through 12 hours of lectures and a 2 hour academic support session.
Please note that lectures are not designed to simply repeat the information
presented here but rather to communicate ideas and themes underlying some
of the concepts of each topic area. Note also that lecturers may decide to
include some additional PPt slides beyond that given on Moodle.
It is strongly recommended that you look through these notes before lectures
as this makes learning easier. You should look at headings, sub headings,
diagrams and tables etc. and look up unfamiliar words.
The key words are often already highlighted in bold and or italics.
You are advised to revise year one Life Science material before the year two
sessions as this knowledge will be assumed by the lecturers.
Support Materials:
The course is supported by a Moodle site. Power Point lecture presentations
will be made available as well as revision materials covering each topic.
Full details of the assessment will be provided on Moodle. :
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Responding to Ill Health NURS08046 – Life Science Notes
THE CARDIOVASCULAR SYSTEM
BRIEF REVISION OF HUMAN CVS
The human cardiovascular (or circulatory) system maintains a continuous flow
of blood to and from all cells of the body, thus ensuring that all cells receive
the nutrients and oxygen they need and that their waste products (e.g. carbon
dioxide) are removed. Thus, it has a very important homeostatic function. It is
made up of three components: the heart, the blood vessels and the blood
itself.
The human CVS is a closed double circulatory system – i.e. the blood is
contained within the blood vessels and there are two separate systems of
blood vessels within it. These are: the pulmonary circulation (concerned
ONLY with carrying the blood to and from the lungs for the purposes of gas
exchange) and the systemic circulation (concerned ONLY with the supply of
oxygen and nutrients to the tissues of
the body and the removal of waste
materials from these tissues.) These
two circulations are anatomically quite
separate from each other, but blood
passes from one to the other in a
defined and ordered manner.
In the pulmonary circulation, which is a
low pressure system, deoxygenated
blood is pumped from the right atrium
of the heart into the right ventricle and,
from there, via the pulmonary arteries,
to the lungs. In the lungs, the blood
gives up its carbon dioxide to, and
picks up oxygen from, inhaled air; it
then returns to the left atrium of the heart
via the pulmonary veins and thus enters the systemic circulation.
UWS Staff (2015)
In the systemic circulation, which is a high pressure system, the newly
oxygenated blood in the left atrium is pumped into the left ventricle and, from
there, via the systemic arteries, to all the tissues of the body to supply them
with oxygen and collect the waste products of their metabolism. After passing
through the tissues, the blood, now deoxygenated and carrying waste
materials, returns to the right atrium via the systemic veins to re-enter the
pulmonary circulation.
The operation of these two linked circulatory systems is clearly
interdependent and notice that both oxygenated blood (in the left side) and
deoxygenated blood (in the right side) is passing through the heart at the
same time. The right and left sides of the heart are quite separate from each
other so that the two types of blood do not mix.
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Responding to Ill Health NURS08046 – Life Science Notes
CONDUCTING SYSTEM OF THE HEART
It is very important that the contraction of all of the muscle cells of the heart
wall is co-ordinated and synchronised so that the pumping action of the
heart is both effective and efficient. There are small groups of specialised
neuromuscular cells within the heart wall that initiate and conduct the
electrical impulse that stimulates the heart to beat. Together, these cells are
referred to as the conducting (or conduction) system of the heart and may
be regarded as a sort of ‘wiring’ system.
Normally, the impulse that initiates the heartbeat arises in a small group of
specialised neuromuscular cells in the wall of the right atrium - the sino-atrial
(SA) node (sometimes called sinus node).
From here, the impulse spreads throughout both atria (causing them to
contract) and reaches another specialised patch of tissue (node) at the top of
wall of muscle tissue that lies between the two ventricles – the
atrioventricular (AV) node.
There is a brief pause in the conduction of the impulse at this node so that
atrial contraction (and thus ventricular filling) is completed before ventricular
contraction begins. A mass of specialised fibres originating from the AV node
(the AV bundle or Bundle of His) cross the ring of fibrous connective tissue
that separates the
two atria from the
ventricles. O
n reaching the
upper end of the
ventricular
septum,
the
Bundle of His
divides into the
right and left
bundle branches.
Then within the
myocardium itself
the
branches
break up into fine
fibres called the
Purkinje fibres.
Madhero88 (2009) Electrical_conduction_system
https://commons.wikimedia.org/wiki/File:Electrical_conduction_system_of_
the_heart.svg?uselang=en-gb
Lynch (2006) Heart right anatomy
http://commons.wikimedia.org/wiki/File:Heart_right_anatomy.jpg?uselang=
en-gb
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Responding to Ill Health NURS08046 – Life Science Notes
Thus from the AV node the impulse passes down into the wall of muscle
tissue between the two ventricles and then passes throughout the walls of
both ventricles, causing them to contract.
As a result of this arrangement, the beating of the four chambers of the heart
is co-ordinated, the two atria contracting first, followed by the two ventricles.
It should be appreciated that the fine cellular structure of the heart is also
important in the conduction of the impulse that initiates the heartbeat: the
cardiac muscle cells of the wall of the heart have a unique structure in that
many of them are branched so that they together form an interconnected
network. Thus, they are able to act as a single functional unit.
It is important to appreciate that all of the cells of the conducting system and
of the heart muscle itself can spontaneously depolarise and initiate a
heartbeat. However, it is the cells of the SA node that do this more quickly
than any other part and thus set the rhythm of the heartbeat. Hence, the SA
node is known as the ‘pacemaker’ of the heart and the rhythm of beating
that originates here is referred to as ‘sinus rhythm’.
Finally, it should be appreciated that no external stimulus needed to initiate or
co-ordinate the heartbeat - the heart is said to show ‘autorhythmicity’ – and
that the factors (e.g. some hormones and nervous inputs), that regulate
the heart rate simply modify this endogenous rhythm.
THE CARDIAC CYCLE
Defined as the events of one heartbeat.
In each heartbeat, the atria and the ventricles each contract and then relax in
co-ordinated fashion to ensure that the heart pumps in a correct and coordinated manner and thus that the body’s circulatory requirements are met.
Two terms need to be defined:
systole -
contraction
diastole -
relaxation
The cardiac cycle can be considered in a number of ways; it will be
considered here as consisting of four parts. It is very important to notice that
the events of this cycle depend crucially on heart structure (especially the
location and orientation of the valves within the heart) and the pressure of
blood in different heart chambers and the blood vessels associated with the
heart at different times.
Clearly, as it is a cycle, it doesn’t really matter at which point a description of
the cardiac cycle begins. Commonly, and for ease of understanding, the point
at which all the chambers of the heart are relaxing (in diastole) and the
ventricles of the heart are filling passively is chosen as the starting point:
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Responding to Ill Health NURS08046 – Life Science Notes
OpenStax College ((2013) Phases_of_the_Cardiac_Cycle
https://commons.wikimedia.org/wiki/File:2027_Phases_of_the_Cardiac_Cyc
le.jpg?uselang=en-gb=en-gb
i) complete diastole -passive ventricular filling
blood enters right & left atria from pulmonary and systemic veins
respectively and then pours passively through open atrioventricular valves
into the respective ventricle. 70% of ventricular filling occurs
atria and ventricles in diastole
atrioventricular valves open, semilunar valves shut
ii) atrial systole
sino-atrial node discharges and thus causes atrial depolarisation and
contraction. remaining 30% of ventricular filling achieved
atria in systole; ventricles in diastole
atrioventricular valves open; semilunar values shut
both atrial and ventricular pressures rise
iii) ventricular systole
impulse for heartbeat passes to ventricular myocardium from
atrioventricular node and thus causes ventricular depolarisation and contraction
ventricular pressure quickly rises, causing atrioventricular valves to shut
when ventricular pressures exceed blood pressure in systemic and
pulmonary arteries, semilunar valves open and blood is expelled into these
arteries
atria in diastole – filling passively; ventricles in systole
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Responding to Ill Health NURS08046 – Life Science Notes
-
ventricular pressure rises dramatically; atrial pressure rises gradually
iv) ventricular diastole
ventricles relax; pressure in ventricles falls and, when ventricular
pressures are lower than pressures in systemic and pulmonary arteries,
semilunar valves shut
when ventricular pressure falls below atrial pressure atrioventricular
valves open and passive ventricular filling occurs
atria in diastole; ventricles in diastole
atrioventricular valves shut, then open; semilunar valves open, then shut
ventricular pressure falls dramatically atrial pressure falls slightly.
TIMINGS IN CARDIAC CYCLE
The heart typically beats about 75 times per minute at rest; thus, each cardiac
cycle takes approximately 0.8 secs to complete. The different parts of the
cycle occupy the following periods:
atrial systole – 0.1 sec
ventricular systole – 0.3 sec
atrial and ventricular diastole (relaxation period) – 0.4 sec
It is the relaxation period is shortened if the heart rate is required to increase
(e.g. in exercise).
THE ELECTROCARDIOGRAM (ECG)
The
generation
of
the
electrical
impulse
that
initiates the heartbeat and
the propagation of this
impulse through the heart
produces electrical activity
that can be detected on the
body surface using sensitive
electrodes.
The
electrocardiogram (ECG) is a
recording of this electrical
activity and is thus a record of
the changes in electrical
activity in different parts of the
heart during the cardiac cycle.
Anthony Atkielski (2007) SinusRhythmLabels
https://commons.wikimedia.org/wiki/File:SinusRhythmLabels.svg?uselang=en-gb
There are three clearly recognisable waves/groups of waves in a typical ECG
recording, each associated with a particular phase of the cardiac cycle:
i)
P wave
small upward wave
related to atrial depolarisation
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Responding to Ill Health NURS08046 – Life Science Notes
ii)
QRS complex
small downward (Q), very large upward (R), small
downward (S) wave but classed as a single “event”
related to ventricular depolarisation
masks activity related to atrial repolarisation
iii)
T wave
moderate upward wave
related to ventricular repolarisation
Appearances of some waves and lengths of intervals between waves is
altered in some disease states: e.g. enlarged Q wave may indicate a
myocardial infarction (MI).
ECG can therefore be of great diagnostic value. And, as it is easy to carry out,
it is widely used clinically.
CORONARY CIRCULATION
Like any living tissue, the heart muscle itself requires an adequate blood
supply. In fact, as the heart muscle is one of the most consistently active
tissues in the body, the heart receives a proportionately greater blood supply
than might be expected from its size – it receives about 5% of the total output
from the left ventricle.
Two large vessels - the left and right coronary arteries – supply the heart
muscle with oxygenated blood. The left coronary artery is greater in diameter
and supplies the left ventricle, whereas the right coronary artery supplies the
right side including the important conducting tissues, the SA and AV nodes.
Blausen Medical Communications, Inc. (2013) Blausen 0260 CoronaryVessels Anterior
https://commons.wikimedia.org/wiki/File:Blausen_0260_CoronaryVessels_Anterior.p
ng
Both the coronary arteries arise from the aorta, just above its origin from the
left ventricle.
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Responding to Ill Health NURS08046 – Life Science Notes
The heart also requires a venous drainage which takes deoxygenated blood
away from the muscle. A network of cardiac veins drain blood away from
the myocardial muscle tissue and eventually all drain into the coronary sinus –
a large vein at the back of the heart – that in turn drains into the right atrium
where the deoxygenated blood that it contains joins with deoxygenated blood
from the rest of the body and enters the pulmonary circulation.
When the heart muscle is contracting, the coronary vessels are compressed
and thus blood cannot easily pass through them. The coronary vessels are
only open when the muscle is at rest (i.e. during diastole), and thus it is in the
relaxation period of the cardiac cycle that blood moves through these vessels.
When the heart rate increases, e.g. exercise, then the period of diastole
shortens thus tending to decrease blood flow. This is in direct conflict with
the needs of the heart, as, like any other muscle, it requires more blood as its
workload increases. Despite this, in fit young healthy individuals, the cardiac
output can be increased by up to five fold (5 L/min to 25 L/min) and heart rate
from ~ 70 b/min to 180 b/min.
In other words, the heart muscle receives enough blood during diastole to
“see it through” systole even when heart rate is high (short diastole).
Blood Pressure
Blood pressure is defined as the pressure exerted by the blood on the wall
of a blood vessel. It is generated by contraction of the ventricles.
Blood pressure varies greatly in different parts of the cardiovascular system
(CVS) – in both the pulmonary and systemic circulations, it is highest in those
vessels that are closest to the heart (pulmonary trunk and aorta respectively)
and falls progressively as the distance from the heart increases. Thus, in the
veins it is very low indeed.
Typically, in clinical usage, unless otherwise specified, the term “blood
pressure” refers to the pressure in the large arteries of the systemic
circulation.
The blood pressure in the large arteries is not constant but pulsatile, reflecting
the alternate contraction (systole) and relaxation (diastole) of the ventricles.
The two extremes of the pulsatile blood pressure measured in the larger
arteries are referred to as the systolic and diastolic pressures, the systolic
clearly being the higher.
Blood Pressure Values
Typical values for these two pressures are 120 mmHg for the systolic and 80
mmHg for the diastolic pressures in young men, 110 mmHg and 70 mmHg
for the same pressures respectively in young women. Blood pressure of a
typical young male would be written as: 120/80 mmHg, that of a typical young
female as: 110/70 mmHg. (mmHg stands for “millimeters of mercury”)
There is, however, a homeostatic range of blood pressure which is perfectly
compatible with health; the normal homeostatic ranges for the systolic and
diastolic pressures are as follows:
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Responding to Ill Health NURS08046 – Life Science Notes
systolic:
diastolic:
90 – 139 mmHg
60 – 89 mmHg.
A blood pressure in which both the systolic and diastolic pressures fall within
these ranges is described as being normotensive. If the systolic pressure is
greater than 139 mmHg and/or the diastolic pressure is greater than 89
mmHg, the subject is said to be hypertensive. If the systolic pressure is lower
than 90 mmHg and/or the diastolic is lower than 60 mmHg, the subject is said
to be hypotensive.
Both hypotension and hypertension are potentially very dangerous conditions,
the former because it may bring about an inadequate blood supply to vital
organs, especially the brain, the latter because it contributes to blood vessel
damage, which can, in turn, together with the high blood pressure, bring about
vessel rupture with consequent severe haemorrhaging and interruption of
blood supply to tissues. Indeed, in many cases of stroke and heart attack,
patients are found to be hypertensive with resultant badly damaged vessels.
Note that blood pressure gradually rises as age increases – this is probably
due to changes in the blood vessels that occur with increasing age.
Determinants of Blood Pressure
The precise value of the blood pressure at any one time depends on two
main factors:
a)
b)
cardiac output - acts to push blood through the blood vessels
peripheral resistance - acts to oppose blood flow through the blood vessels
If the value of one (or more) of these factors increases, then blood pressure
itself will increase; similarly, if the value of one (or more) of these factors
decreases, then blood pressure itself will decrease. Note, long-term
regulation of blood pressure also depends on blood volume, which is
regulated by the kidney.
Cardiac Output
This is defined as the volume of blood ejected from the left (or right) ventricle
into the aorta (or pulmonary trunk) per minute. It is calculated as follows:
cardiac output = heart rate (beats min-1) x stroke volume (ml)
The stroke volume is defined as the amount of blood ejected by the relevant
ventricle at each systole i.e. how volume of blood that leaves one ventricle
following one contraction.
At rest, typically, the heart rate is 75 beats min-1 and the stroke volume of
each ventricle is about 70 ml.
Thus the cardiac output into either the pulmonary or systemic circulation is:
75 x 70 ml/min = 5250ml/min (5.25l/min).
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Responding to Ill Health NURS08046 – Life Science Notes
Both the heart rate and the stroke volume can be readily and rapidly changed
(e.g. during exercise), thus causing a change in the cardiac output. Hence,
variations in the cardiac output can be used as a rapid mechanism to control
blood pressure.
Venous return (the amount of blood returning to the heart from the veins) is
also important in maintaining blood pressure: cardiac output is largely
determined by the degree of filling of the ventricles during diastole and this, in
turn, depends on adequate venous return. A reduced venous return will lead
to reduced ventricular filling, thus to a reduced cardiac output and reduced
blood pressure.
Peripheral Resistance
This is defined as the sum total of all the vascular resistances that oppose
blood flow. Resistance to flow depends on various factors (blood vessel
length, blood viscosity), but is only regulated by vessel radius: the smaller
the vessel radius, the greater the resistance to flow – this can readily be
varied by altering the degree of muscular contraction of the vascular smooth
muscle – and thus is the major mechanism by which variation in peripheral
resistance is brought about. Most resistance to blood flow occurs in the
arterioles and thus these vessels have a very important role in controlling the
peripheral resistance and thus, in turn, blood pressure.
The peripheral resistance too can be readily and rapidly changed, mainly by
varying the diameter of blood vessels (e.g. of the arterioles). Hence, variations
in the peripheral resistance can be used as a rapid mechanism to control
blood pressure.
Factors that Regulate Blood Pressure
Many factors can affect the blood pressure. They can act on the heart (to vary
cardiac output) and/or on the blood vessels (to vary peripheral resistance)
and, if they act on both, will act in complementary ways. They include:
i)
The autonomic nervous system (ANS):
the sympathetic division of the ANS acts to increase blood pressure by
increasing both the cardiac output and the peripheral resistance.
The parasympathetic division acts to decrease blood pressure by
reducing cardiac output (no effect on peripheral resistance).
ii)
Hormones. e.g. adrenalin – causes an increase in blood pressure by
both increasing cardiac output and peripheral resistance. Some endocrine
(hormone) systems affect the blood volume and thus can affect blood
pressure. They include the renin/angiotensin system and anti-diuretic
hormone (ADH).
iii)
Temperature - increased body temperature (e.g. fever) increases
blood pressure as it causes an increase in the heart rate and thus cardiac
output decreased body temperature has the opposite effect
iv) Emotions – effects from higher brain centres. Emotions (e.g. anger,
fear, anxiety) cause an increase in blood pressure by increasing both the
cardiac output and peripheral resistance. Others (e.g. grief, depression)
cause a decrease in blood pressure by decreasing both the cardiac output
and peripheral resistance.
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THE ENDOCRINE SYSTEM
Introduction
The endocrine system consists of glands widely separated from each other
with no direct links (Figure below). Endocrine glands consist of secretory
cells surrounded by an extensive network of capillaries that allows
effective distribution of hormones from the secretory cells into the
bloodstream. The hormone is then carried in the bloodstream to target tissues
and organs where they affect cellular growth and metabolism.
Homeostasis of the internal environment of the body is maintained by a
combination of the autonomic nervous system (see CNS section) and the
endocrine system. The autonomic nervous system can rapidly change
conditions while hormones of the endocrine system evoke slower more
precise adjustments.
United States Government (2005) The endocrine
system
http://commons.wikimedia.org/wiki/Endocrine_syst
em?uselang=engb#mediaviewer/File:Illu_endocrine_system.jpg
Hormone action
Hormones function by binding to hormone-specific receptors in the target
cell. Binding of the hormone and receptor acts as a switch, able to alter the
chemical or metabolic reactions inside the cell. Receptors may be found on
the cell surface or inside the cell.
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The Endocrine Pancreas and Control of Blood Glucose
 The pancreas is a large dual gland which has both an exocrine (ducted)
and endocrine (ductless) components.
 It consists of a broad head, a body and a tail. The head lies in the curve of
the duodenum.
 The exocrine role of the pancreas involves the generation of digestive
juices that enter the small intestine via the pancreatic duct.)
 There are, however, groups of endocrine cells distributed throughout the
gland, known as the islets of Langerhans, which secrete hormones which
control the concentration of blood glucose
BruceBlaus (2013) PancreaticTissue
https://commons.wikimedia.org/wiki/
File:Blausen_0701_PancreaticTissue.
png
There are no ducts associated with these cells, and hormones are secreted
directly into the bloodstream and circulate around the body

There are two main types of cells within the pancreatic islets


 (alpha) cells secrete glucagon
 (beta) cells secrete insulin
There are other hormones which can affect blood glucose levels – but these
will not concern us here.
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The actions of glucagon and insulin are antagonistic, that is the hormones
affect blood glucose levels in opposite directions. This often occurs when tight
control is needed.
 glucagon increases blood glucose levels
 insulin decreases blood glucose levels
Some of the main ways in which this is achieved are summarised in the table
below:
Insulin lowers blood glucose
Glucagon increases blood glucose
Stimulates uptake of glucose by cells
Facilitates release of glucose into blood
Increases conversion of glucose to
glycogen (glycogenesis)
Decrease conversion of glucose to
glycogen (glycogenesis)
Decreases breakdown of glycogen to
glucose (glycogenolysis)
Stimulates glycogenolysis
Prevents breakdown of protein & fat
and formation of new sugar from e.g.
protein( gluconeogenesis)
Stimulates gluconeogenesis
Regulation of Pancreatic Hormones
Pancreatic hormone secretion is regulated directly by blood glucose levels.


Secretion of insulin is stimulated by increased blood glucose levels
Secretion of glucagon is stimulated by decreased blood glucose levels
So although insulin and glucagon have opposing effects on blood glucose
concentration they work together to ensure that blood glucose levels do not
become too high (hyperglycaemia) or too low (hypoglycaemia). Both
conditions are detrimental to health.
Disorders of pancreatic islets
Diabetes mellitus is a very common disorder of the pancreatic islets which
results from a malfunction of the hormonal control of glucose metabolism.
Briefly, there are two variants of this disorder:
 Type I or insulin dependent diabetes mellitus (IDDM)
This occurs mainly in children and young people, and is characterised by the
deficiency or absence of insulin, because of the destruction of  cells in the
pancreatic islets (often resulting from an autoimmune reaction).
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 Type II or non-insulin dependent diabetes (NIDDM)
The most common form of diabetes, accounting for about 90% of cases,
NIDDM usually occurs in older people many of whom are obese. The causes
of NIDDM are complex and multifactorial, but include genetic and lifestyle
(poor diet and obesity) components. In NIDDM, insulin levels may be normal
or even unusually high. Insulin resistance means that insulin binding to
receptors does not invoke the normal changes inside target cells, and
responses such as glucose uptake into cells are therefore not stimulated
properly.

A similar condition to NIDDM arises in 2-5% of pregnancies, called
Gestational Diabetes Mellitus (GDM). GDM appears to be characterised by
insulin resistance, which in this case may be due to blocking of insulin by
pregnancy-related hormones. The condition often disappears following
delivery, but approximately 20-50% of women who suffer GDM develop
NIDDM in later life.
Pituitary Gland
The pituitary gland and hypothalamus act as a unit regulating the activity of
most of the other endocrine glands. The pituitary is found behind the
hypothalamus in the brain and is the size of a pea. It has 3 distinct parts;
anterior pituitary, posterior pituitary and intermediate lobe.
Role of the anterior pituitary
Hormones from the anterior pituitary control secretion by other endocrine
glands while others have direct effects on target tissues.
EXAMPLES
Growth hormone (GH) – most abundant hormone synthesised by the anterior
pituitary. Stimulates cell growth and division particularly bone and skeletal
muscles.
Prolactin – stimulates milk production.
Thyroid stimulating hormone (TSH) – stimulates growth and activity of the
thyroid gland.
Adrenocorticotrophic hormone (ACTH) - stimulates production and release of
hormones from the adrenal glands.
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Adrenal Glands
The two adrenal glands lie at the upper end of each kidney and are about 4cm
long and 3cm wide. They are each composed of two portions, the outer
adrenal cortex and the inner adrenal medulla.
EEOC (2006) adrenal_gland
https://commons.wikimedia.org/wiki/Fil
e:Illu_adrenal_gland.jpg
Adrenal Cortex
The adrenal cortex produces 3 groups of steroid based hormones from
cholesterol which are collectively known as adrenocorticoids.
1.
Glucocorticoids; e.g. Cortisol (hydrocortisone) which regulates
metabolism and response to stress.
2.
Mineralocorticoids; e.g. Aldosterone which regulates osmotic balance.
3.
Sex hormones; e.g. Androgens - insignificant compared to those
produced by testes/ovaries in adulthood.
Adrenal Medulla
Stimulated by its extensive sympathetic nerve supply to produce adrenaline
and noradrenaline. Released into the blood stream from the adrenal medulla
after stimulation of the sympathetic nervous system, these two hormones
potentiate the fight or flight response by;

Increasing heart rate

Increasing blood pressure

Diverting blood to essential organs e.g. heart, brain and skeletal
muscles

Stimulating glycogenolysis ( conversion of glycogen to glucose)
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Adrenal disorders
Hypo and hyper secretion occurs including:
Addison’s disease – hyposecretion of glucocorticoids resulting in serious
weakness and collapse under stress.
Cushings syndrome-hypersecretion of glucocorticoids resulting in oedema
(moon face), hyperglycaemia, hypertension, immunosuppression.
N.B these are also side effects of steroid treatments which involve giving
glucocortico steroids for their anti-inflammatory effects. Cushing’s disease
produces the same syndrome but is caused by the pituitary gland producing
excess ACTH (corticotropin).
Patients on steroids produce little ACTH due to negative feedback and
therefore their own adrenal glands are suppressed. Stopping steroid
treatment suddenly leads to adrenal insufficiency and susceptibility to
collapse. Such patients should carry ID so that in the event of an accident
steroids can be given or even increased to cope with the stress.
Conn’s syndrome-hypersecretion of aldosterone leading to increased
plasma sodium, water retention, leading to hypertension and potassium
depletion.
Phaeochromocytoma-is a tumour producing excess adrenaline or
noradrenaline leading to hypertension, tachycardia, anxiety etc.
Kidney
Hormones that influence the function of the kidney, specifically, anti-diuretic
hormone (ADH) and renin-angiotensin- aldosterone system are discussed
in the next section.
The kidneys also produce the hormone erythropoietin when plasma oxygen
levels are low and the erythropoietin stimulates red bone marrow to produce
erythrocytes (RBC). Athletes train at altitude where oxygen is low deliberately
to stimulate erythropoietin EPO this is not cheating but injecting EPO is.
Renal failure patients become anaemic which used to require blood
transfusion before EPO became widely available for injection
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THE URINARY SYSTEM
INTRODUCTION
The focus in this second year module will be on physiology of the
urinary/renal system. Knowledge of the anatomy and basic functions of the
urinary and endocrine systems from previous modules will be assumed.
Renal Disease will be dealt with in the associated nursing modules but
students should already expect that people with renal disease may develop
problems such as:


Fluid balance problems,
Waste accumulation such as uraemia (excess urea in blood)
FUNDAMENTAL CONCEPTS
You need to understand basic principles of fluid movement in the body
especially osmosis, diffusion, filtration and active transport. You need to
understand the concept of concentration and units such as mmol /l
(pronounced milli-molar). See early chapters of Life Science text books
OVERVIEW OF URINARY SYSTEM FUNCTION
The urinary system aids HOMEOSTASIS principally by EXCRETING URINE
Water
(95% of volume)
Nitrogenous Waste: mainly UREA, a little URIC ACID.
Ions (salts/electrolytes), such as: Na+, Ca++, K+, Mg++, NH4+, H+, Cl-, PO43-, HCO3Functions of the Urinary System
Excretion of nitrogenous wastes.
Regulation of blood pH (re. H+)
Regulation of Blood Electrolyte balance
Regulation of Blood Volume
Regulation of Blood Pressure: Renin from kidney also increases BP
Production of hormones: Calcitriol which regulates calcium
homeostasis and erythropoietin which stimulates red blood cell production.
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Responding to Ill Health NURS08046 – Life Science Notes
Three main processes are involved in the production of urine:
1) FILTRATION
2) SELECTIVE
REABSORPTION
3) TUBULAR
SECRETION
Once formed the
urine remains
unchanged in
composition as it is
excreted from the
nephron in the
kidney to travel to
the urinary bladder.
Madhero88 (2010)
Physiology of Nephron
https://commons.wikim
edia.org/wiki/File:Physi
ology_of_Nephron.png
A primary function of the urinary system is the excretion of nitrogenous
wastes
Protein molecules are made from amino acids which contain Nitrogen Atoms
(N) in addition to Carbon, Oxygen and Hydrogen. When the body catabolises
(breaks-down) amino acids in addition to CO2 and H2O nitrogenous waste,
such as AMMONIA (NH3), is produced. This process is known as
DEAMINATION and the ammonia is highly toxic and is converted in the liver
to UREA (which is less toxic, but still must be removed. )
The urea from the liver enters the blood, is carried to the kidneys where it is
filtered into the glomerular filtrate. Because urea is not selectively
reabsorbed most urea passes out into the urine.
Patients with advanced Liver disease cannot convert toxic ammonia into
safer urea and may suffer from encephalopathy ( a type of brain dysfunction)
due to build-up of Ammonia.
Patients with advanced Kidney disease can make Urea but cannot excrete it
so may die from uraemia (urea in the blood) due to build up of urea.
Other nitrogenous wastes include URIC ACID which comes from the
breakdown of nucleic acids like DNA. Excess uric acid in blood causes
Gout which may be associated with rapid cell destruction in malignancy or
failure to excrete uric acid as in kidney disease.
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Responding to Ill Health NURS08046 – Life Science Notes
ANATOMY OF URINARY SYSTEM (see year one notes)
Blood Supply
Each kidney receives a very profuse blood supply approx. 1200ml/min
amounting to one quarter of cardiac output via the RENAL ARTERY which
branches as it passes through the pelvis and the medulla on the way to the
cortex. In the cortex the arteries form many GLOMERULI, tufts of capillaries
where filtration of blood takes place. The blood then flows into the
PERITUBULAR CAPILLARIES (which surround the nephrons) and is drained
into the RENAL VEIN.
OpenStax College (2013) Blood Flow in the Kidneys
https://commons.wikimedia.org/wiki/File:2612_Blood_Fl
ow_in_the_Kidneys.jpg
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Responding to Ill Health NURS08046 – Life Science Notes
Nephron Structure & Function
Each kidney contains around one million nephrons. The nephron, a tubular
structure, is responsible for the filtration of the blood to form urine. Nephrons
are comprised of 5 sections:
1) Bowman’s capsule
Blood is forced through the glomerular capillaries under relatively high
pressure. The porous walls of capillaries allow blood plasma (minus the
plasma proteins) to pass out of the capillary into the Bowman’s capsule. The
FORMED ELEMENTS and plasma proteins remain within the capillary. The
fluid that enters the Bowman’s capsule is now called GLOMERULAR
FILTRATE or ULTRAFILTRATE.
GLOMERULAR CAPILLARY PRESSURE is approx. 55mmHg because of the
arrangement of the afferent and efferent arterioles.
Henry Gray (1918) Gray1130
https://commons.wikimedia.org/wiki/File:G
ray1130.svg + UWS Staff (2015)
humanphysiology2011.wikispaces.com
The above diagram demonstrates some of the opposing forces that are found
in Bowman’s capsule – which ultimately lead to formation of glomerular
filtrate. .
Glomerular capillaries have an extremely high pressure which would normally
burst except they are covered by a layer of specialised CAPSULAR
EPITHELIUM. The specialised PODOCYTE cells of the capsular epithelium
act like an interlocking mesh with slits to allow filtration of the blood. Cells and
plasma proteins are too big to go through slits and stay in the blood stream do
not pass into the capsule. The capillary walls also have holes, or
fenestrations, allowing small plasma components through. Between these
layers is a basement membrane, which repels proteins due to their negative
charge.
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Responding to Ill Health NURS08046 – Life Science Notes
Damage to the capsular epithelium as caused by hypertension or poisons
or infection results in wider “holes” in the filter so plasma proteins pass into
the filtrate and are detectable as proteinuria during urine testing.
Therefore in normal health glomerular filtrate is virtually identical to plasma
except lacking plasma proteins
The GLOMERULAR FILTRATION RATE (GFR) is approx. 120ml per minute
of which 119ml are reabsorbed. i.e. most of the fluid that is found in the
glomerulus will be reabsorbed back into the blood. Reabsorption occurs
throughout the remainder of the nephron. The reabsorbed materials are and
returned to the blood in the PERITUBULAR CAPILLARIES which surround
the nephron.
Reabsorption may be passive or active.
PASSIVE PROCESSES do not require extra energy. Passive processes
depend on concentration or pressure gradients. Fluid moves from higher
pressure to lower pressure and substances diffuse from higher concentration
to lower concentration. Osmosis is diffusion of water.
ACTIVE PROCESSES involves cells “pumping” substances against a
concentration gradient. Active transport requires the expenditure of energy.
Glucose is actively transported from filtrate back to plasma and sodium is
usually pumped out of plasma
Note:
DIFFUSION is the movement of a substance from an area of high
concentration to an area of lower concentration until equilibrium is
reached.
OSMOSIS is the movement of WATER from an area of HIGH WATER
CONCENTRATION (low solute concentration) to an area of LOW
WATER CONCENTRATION (high solute concentration) through a
SEMI PERMEABLE MEMBRANE until equilibrium is reached.
PLASMA PROTEINS play a big role in OSMOSIS because they are
not normally filtered through capillaries and therefore the solute
concentration is higher in plasma than filtrate and Water
concentration is lower in plasma
N.B. The concentration of solutes such as glucose and sodium is the
same in the blood plasma as it is in the filtrate in the capsule. This
means that due to plasma proteins the PLASMA OSMOTIC
PRESSURE is higher by 30mmHg and acts to resist filtration as does
the pressure of the HYDROSTATIS PRESSURE of the FILTRATE
15mmHg in the capsule.
N.B Osmotic pressure is sometime a bit confusing as a high osmotic
pressure pulls water.
NET FILTRATION PRESSURE = GLOMERULAR BLOOD
BRESSURE – (PLASMA OSMOTIC PRESSURE + CAPSULAR
FILTRATE PRESSURE) = 10mmHg
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Responding to Ill Health NURS08046 – Life Science Notes
A similar process occurs in TISSUE FLUID which is formed by filtration
of plasma through ordinary capillaries into tissue space. Without the
plasma proteins exerting an osmotic pressure pulling water back from
the tissue spaces the fluid accumulate in the tissue and low plasma
protein levels are one cause of OEDEMA.
This is seen in starvation when children have low protein intake and
their livers have no amino acids to make into plasma protein, liver
disease when the liver cannot make plasma protein and nephritic
syndrome when the kidney is damaged and allows plasma proteins to
be lost in the urine.
2) Proximal Convoluted Tubule (PCT)
SELECTIVE REABSORPTION of the filtrate commences here! Useful
substances are taken out of the filtrate and returned to the peritubular blood
capillaries which surround the PCT. By the end of the PCT about 65% of
filtered salt (NaCl) and water are reabsorbed. Most filtered nutrients (amino
acids, glucose) are also reabsorbed in the PCT. The substances not
reabsorbed such as UREA now pass into the loop of Henle.
Glucose and salt are actively transported from the filtrate into the plasma by
the cells of the PCT which use a lot of energy.
As plasma moves along the peritubular capillaries the plasma concentration of
Glucose and salt (solutes) get higher and plasma water concentration in gets
lower than that in the filtrate in the PCT. As such Water moves passively by
OSMOSIS from the PCT to Plasma in PERITUBULAR CAPILLARIES.
In DIABETES MELLITUS so much glucose is filtered into the PCT that the
PCT cannot reabsorb all the glucose back into the plasma. This is called
exceeding the RENAL THRESHOLD and glucose is passed out in urine
(GLYCOSURIA). This means that less water is reabsorbed by osmosis
and hence more water passes out in the urine. This POLYURIA is due to
OSMOTIC DIURESIS. In fact the word diabetes means fountain and mellitus
means honey. So people with diabetes mellitus pass lots of sweet urine.
3) Loop of Henle
The loop of Henle is where a further 20%, of the salt and water are
reabsorbed from the filtrate. The sodium reabsorbed from the loop of Henle
makes the solute concentration in the medulla high and this helps water
reabsorption by osmosis from the adjacent collecting ducts.
4) Distal Convoluted Tubule (DCT)
Up until now the reabsorption of Na+ and Cl- was fixed i.e. the amount
absorbed was independent of the body’s needs.
The DCT is responsible for the final absorption of Na+ but it can now be
regulated by the hormone ALDOSTERONE. Aldosterone is secreted by the
ADRENAL GLANDS (which lie on top of the kidneys). Aldosterone promotes
the REABSORPTION of Na+ by the DCT by an active transport mechanism in
exchange for secretion of K+.
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Responding to Ill Health NURS08046 – Life Science Notes
ALDOSTERONE secretion is regulated by the kidneys. When Blood
Pressure, Blood Volume or Blood Sodium are low the kidney secretes an
enzyme called RENIN which activates an inactive plasma protein
ANGIOTENSINOGEN to become ANGIOTENSIN 1. ANGIOTENSIN
CONVERTING ENZYME found in lungs and other tissues convert
angiotensisin 1 to ANGIOTENSIN 2. Collectively this is known as the reninangiotensin system and this plays a vital role in the control of blood
pressure.
UWS Staff (2015)
ANGIOTENSIN 2 is a powerful vasoconstrictor leading to raised blood
pressure and also stimulates aldosterone secretion from the adrenal
cortex. Increased sodium reabsorption in the DCT leads to increased water
reabsorption by osmosis. The combined effects of all this renin angiotensin
action increases Blood Pressure.
Tubular Secretion also occurs in the DCT which is the active “pumping” of
unwanted substances into the urine that would otherwise stay in the blood.
Many drugs and toxins are excreted this way
Hydrogen (acid) ions (H+) and are removed from the plasma by tubular
secretion when the pH of the blood is too low. At the same time Bicarbonate
ions HCO3- (alkaline) are reabsorbed into plasma to help neutralise acidity.
People with kidney disease have difficulty maintaining the pH of the plasma
between 7.35 and 7.5 and often are have acidosis.
Summary of events of aldosterone: if the body is short of Na+ then
aldosterone blood levels increase which promotes reabsorption of Na + and
therefore all or most the Na+ entering the DCT will be absorbed. If the body
has too much Na+, then aldosterone levels drop and the absorption of Na + is
incomplete and Na+ is lost in the urine.
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Responding to Ill Health NURS08046 – Life Science Notes
5) Collecting Duct (CD) - receives what is left of the filtrate from the DCTs of
many nephrons. The CD passes down through the medulla and drains into
the renal pelvis. The CD is responsible for the final reabsorption of water,
and like the DCT, this process is regulated by a hormone called
ANTIDIURETIC HORMONE (ADH), produce by the POSTERIOR
PITUITARY GLAND.
ADH works by making the gaps bigger between cells lining the collecting duct
making the duct more porous with more osmosis of water from the collecting
duct into the peritubular capillaries of the medulla and hence less water
leaves the body in the urine. The urine may thus be more concentrated.
People lacking sufficient ADH have DIABETES INSIPIDUS a condition in
which results in high output of dilute (insipid) urine.
Summary of events of ADH:
If you drink too much fluid (over-hydrated) - the levels of ADH drop, less water
is reabsorbed and large volumes of dilute urine are produced. Conversely, if
dehydrated, the body produces - large amounts of ADH and maximal
absorption of water occurs.
HYPERTENSION may be caused by excess ADH increasing blood volume
and/or by excess Aldosterone which causes sodium retention.
Hypertension is a both a cause and effect of renal disease and patients with
kidney disease may enter a vicious cycle of positive feedback called
MALIGNANT HYPERTENSION.
Urine Some water has to be lost in the urine to excrete nitrogenous wastes.
The minimal daily production of urine is about 1.5 litres. Once the filtrate
leaves the collecting duct it is now urine and its composition cannot be
altered.
In addition to urea, creatinine, potassium, and ammonia, other typical solutes
found in the urine include: uric acid, sodium, chloride, magnesium and
calcium ions. If disease alters body metabolism or kidney function, traces of
other substances not normally present, may appear in the urine e.g. ketone
bodies in diabetes.
A patient who is drinking normal amounts will produce approx. 1ml of urine
per minute (60ml per hour) and therefore approx. 1500ml a day. Any UWS
producing less than 30ml per hour is a cause for concern.
A healthy bladder holds 300ml to 400ml or more so unless drinking a lot a
person should only need to pass urine four or five times a day. Passing urine
unnecessarily can lead to reduced bladder capacity and result in frequency
and urgency.
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Responding to Ill Health NURS08046 – Life Science Notes
WATER AND ELECTROLYTE BALANCE
Around 60% of the average
adult male body weight is
due to water. This water is
distributed throughout the
body, inside and outside
the cells. Dissolved in the
water are many electrolytes
(salts, ions) all of which
have an important role in
contributing to the normal
osmotic pressure of body
fluids. In addition, most
electrolytes play a major
role in regulating essential
body
processes
(more
details below)
UWS Staff (2015)
BODY FLUID COMPARTMENTS
The Total Body Water (TBW) of a 70Kg male will be around 42 litres (i.e. 60%
of 70Kg).
Women and obese men have a lower proportion of water because of their
tendency to have a body composition with more fat. A 70kg woman may have
a 55% body water 38 litres. This is one reason why the recommended alcohol
limit has fewer units for women.
Intracellular Fluid (ICF).
Most of the body water is found in the cytoplasm of the body cells – roughly
28 litres.
Extracellular Fluid (ECF).
The remaining water (roughly 14 litres) is found outside the cells and is
distributed as:
-interstitial Fluid (Tissue Fluid) - the fluid in the spaces between the cells
(about 10- 11 litres)
-Blood Plasma - contained within the circulatory system (about 3 - 4 litres)
Please note that there is relatively free movement of water between the fluid
compartments i.e. if you were able to trace the movement of an individual
water molecule it could be found “moving” around the body in and out of any
of these compartments.
WATER BALANCE
In order to avoid overhydration or dehydration individuals must stay in
water balance. Normally water loss and water gain are both approximately
equal to 2500ml.
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Responding to Ill Health NURS08046 – Life Science Notes
Water Gain
Water Loss
Metabolism (200 ml)
Food (700 ml)
Drinking (1600 ml)
Faeces (100 ml), Exhaled (300 ml)
Evaporation from skin (600 ml)
Urine (1500 ml)
Factors leading to Dehydration are (a few examples) inadequate fluid intake,
sweating, diabetes mellitus or diabetes insipidus can increase urinary
water loss substantially, diarrhoea - the absorption of water by the large
intestine is impaired, diuretics - may be prescribed to reduce systemic or
pulmonary oedema or high blood pressure
Factors leading to Overhydration:
- excessive fluid intake. Especially if taken with high levels of salt (NaCl).
- insufficient excretion of water by the kidney. Could be due to partial kidney
failure or overproduction of ADH by the pituitary gland.
ELECTROLYTE BALANCE
Although there are many different electrolytes dissolved in the body fluids,
only Sodium (Na+), Potassium (K+) and Calcium (Ca2+) will be considered for
the moment.
Sodium
Correct ECF levels (around 140 -150 millimoles per litre) of sodium are
essential for normal nerve and muscle function and for regulating total ECF
(including plasma) volume. If too much sodium is retained in the body then
extra water is also retained in order to keep the osmotic pressure of the body
fluids correct. As a result ECF (and plasma) volume increases leading to an
increase in blood pressure (hypertension). Conversely, if there is too little
sodium body fluids are lost, again to maintain the correct the osmotic
pressure. As a result ECF volume decreases and blood pressure drops
(hypotension).
Potassium
The ECF levels of potassium are usually very low (between 3.5 and 5.0
millimoles per litre). Most of the potassium is inside the body cells and, like
sodium, is essential for normal nerve and muscle function. The heart is
particularly susceptible to changes in potassium levels and potassium chloride
injections are used in judicial executions in USA.
Calcium
Vitamin D is necessary for Calcium absorption. Most of the body calcium is
stored in bone, however, it is found both in the ECF and ICF and plays many
important roles: involved in the contraction process of muscles, nerve
function. Hypocalcaemia produces muscle spasms (tetany) due increased
excitability of nerve and muscle tissue and can also in the long term lead to
demineralisation of bone.Hypercalcaemia reduces excitability of nerve and
produces muscle weakness. There is also the risk of kidney stones.
Parathyroid hormone (from the parathyroid glands) is mainly responsible
for regulating calcium levels
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Responding to Ill Health NURS08046 – Life Science Notes
THE RESPIRATORY SYSTEM
Introduction
The main function of the respiratory system is to enable oxygen to move from
air into the blood and carbon dioxide to move in the opposite direction. It
also has other functions, such as the metabolism of some compounds, the
filtration of toxic materials from the circulation, and to act as a reservoir for
blood.
Structure of the respiratory system
LadyOfHats (2007) Respiratory_system
https://commons.wikimedia.org/wiki/File:Respiratory
_system_complete_en.svg
The respiratory system (or tract) can be divided into upper and lower parts.
The nose, mouth, pharynx and associated structures make up the upper
part of the respiratory tract; the larynx, trachea, bronchi and lungs make up
the lower part of the tract.
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Responding to Ill Health NURS08046 – Life Science Notes
Function of upper respiratory tract structures
The nasal, pharyngeal and laryngeal cavities act to filter, heat and moisten
air that passes through it. The membranes of these cavities possess a rich
blood supply and can produce copious mucous secretions to trap any
impurities. These chambers are also intimately involved in the functions of
smell and speech (not to be considered here).
At the entrance to the trachea and oesophagus there is a small mobile flap of
cartilage called the epiglottis that blocks the trachea during swallowing to
prevent food entering the windpipe.
Structure of the lungs & the pleura
Each lung is divided into lobes made up of segments and then subdivided
further into lobules. Each lung is covered on its outer surface by a thin layer
of very smooth epithelial tissue called the visceral pleura which turns back
on itself to form a layer of parietal pleura which lines the inside of the chest
wall. Between these two layers is the pleural space or cavity, which
contains some watery (serous) lubricating fluid. This arrangement allows the
lungs to expand and deflate inside the chest with very little frictional
resistance.
OpenStax College (2013) 2313 The Lung Pleurea
https://commons.wikimedia.org/wiki/File:2313_The_
Lung_Pleurea.jpg
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Responding to Ill Health NURS08046 – Life Science Notes
The airways and air flow
The passages that conduct air into and out of the lungs (the airways) consist
of a series of branching tubes which become progressively narrower, shorter
and more numerous as they go deeper into the lungs.
The trachea is the tube that runs down from the pharynx through the neck into
the chest; it is about 10cm long, about 1.8cm in diameter and is made of
connective tissue and smooth muscle. It is held open by C-shaped rings of
strong cartilage. Like most of the respiratory tract below it, it is lined with
ciliated epithelium which can transport mucus and trapped particles upwards
to the epiglottis for swallowing.
1. Trachea
2. Mainstream bronchus
3. Lobar bronchus
4. Segmented bronchus
5. Bronchiole
6. Alveolar duct
7. Alveolus
United States Government (2006) Illu quiz lung.
http://commons.wikimedia.org/wiki/File:Illu_quiz
_lung05.jpg
The trachea divides within the
chest into right and left main
(or primary) bronchi. The right bronchus is slightly larger and more vertical
than the left; hence, it is the right main bronchus that is more likely to become
obstructed by an inhaled foreign body. These bronchi are held open by
incomplete rings of cartilage and they divide into the smaller secondary and
then tertiary bronchi.
This branching continues down to the terminal bronchioles which are the
smallest airways without alveoli. The airways down to this point in the
respiratory tract take no part in gas exchange and are thus referred to as the
anatomical dead space; they together contain about 150 ml of air.
The terminal bronchioles divide into respiratory bronchioles which have
occasional alveoli budding from their walls. These eventually come to form
alveolar ducts which are completely lined with alveoli.
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Responding to Ill Health NURS08046 – Life Science Notes
This alveolated region of the lung where the gas exchange occurs is known
as the respiratory zone. The respiratory zone of each lung is about 2.5 to 3
litres in volume.
Ventilation
INSPIRATION: air only flows from a region of high pressure to one of low
pressure. During the intake of air into the lungs (inspiration) the volume of
the chest (thoracic) cavity is increased; this reduces the intrathoracic
pressure to below that of the external atmosphere and thus air is sucked into
the lungs (to the level of the terminal bronchioles). At rest, the increase in
the volume of the chest cavity is brought about almost completely by the
diaphragm contracting and pulling down - this increases the top-to-bottom
dimension of the chest cavity.
In situations where an increased respiratory effort is required, other muscles
can be used to aid expansion of the chest. These include the external
intercostal muscles, which pull the ribs upwards and outwards, thus
increasing the transverse dimension of the chest and the volume of the chest
cavity and some muscles of the head and neck, such as the scalene muscles
that lift the first two ribs, and the sterno(cleido)mastoids which raise the
sternum. These latter muscles increase the antero-posterior dimension of the
chest and thus again the volume of the chest cavity.
At the level of the terminal bronchioles, the cross-sectional area of the airways
is so enormous that the speed of airflow becomes very slow. At this point
diffusion takes over as the main mechanism of ventilation and the distance to
the alveoli (which is very short) is then traversed in about a second.
EXPIRATION: the lung contains much elastic tissue and so it returns passively
to its initial volume when the inspiratory muscles rest. This passive recoil
compresses the air in the lungs to a higher pressure than outside and so air
flows out of the lungs - this is the means by which expiration is achieved at
rest.
During exercise, expiration also becomes an active process. The muscles of
the abdominal wall contract, increasing intra-abdominal pressure and
pushing the diaphragm upwards. The internal intercostal muscles act to
pull the ribs down and inwards. Both these actions cause a decrease in the
thoracic volume and thus assist expiration.
Factors affecting ventilation
Compliance refers to how much effort is required to expand the chest wall
and inflate the lungs. The lungs are normally very easy to inflate – they are
said to have high compliance.
Airway resistance is the resistance posed to airflow by the walls of the
airways. This is normally low, and thus the pressure required to move air
through the airways is also very small.
Surface tension of the alveolar fluid: the surface of the alveoli in contact
with the air is lined with a watery liquid to permit gas exchange. This liquid
layer should cause the alveoli to collapse due to its surface tension. However
some of the alveolar cells secrete a material called surfactant which acts like
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Responding to Ill Health NURS08046 – Life Science Notes
a detergent to dramatically lower the surface tension of the alveolar lining
layer and thus prevent alveolar collapse. If surfactant is reduced or absent,
then many alveoli collapse on expiration and the effort required to expand the
lung at each inspiration is greatly increased. An example of this is respiratory
distress syndrome, when premature infants do not produce sufficient
surfactant to keep a large proportion of alveoli inflated after expiration.
Since normally the lungs have high compliance and airway resistance is low,
the energy expenditure associated with normal breathing is low. If, however,
something occurs to lower lung compliance (e.g. presence of scar tissue in
the lung) and/or to raise airway resistance (e.g. inflammatory swelling of the
airway epithelium), then the effort required to maintain an adequate
respiratory effort can become considerable.
Lung volumes
The total capacity of the lungs is about 6 litres. The tidal volume is the
volume of air moved into and out of the lungs at each inspiration and
expiration; at rest this is about 0.5l. The volumes of air that can be inspired or
expired over and above the tidal volume are known as the inspiratory and
expiratory reserve volumes respectively. The maximal volume that can be
exhaled is known as the vital capacity (about 4.8l.). However, some gas
remains in the lungs even after a maximal expiration; this is called the
residual volume (about 1.2l) and it represents the air in the anatomical dead
space and air remaining in the alveoli to keep them open.
The minute volume is the total volume of air inhaled and exhaled each
minute and is calculated as follows:
minute volume (L/min) = tidal volume(L) x respiratory rate (breaths/min)
At rest, the average number of breaths per minute is about 12 and the tidal
volume is 0.5l; thus the minute volume is 0.5 x 12 = 6 l/min. However, when
the dead space (150ml) is taken into account, only (500-150) x 12 = 4.2l/min
is actually fresh air available for gas exchange.
Note that the tidal and minute volumes can be increased dramatically if the
body’s demand for oxygen increases.
The blood-air interface & diffusion
Oxygen and carbon dioxide move between air and blood by simple
diffusion along their concentration (pressure) gradients, i.e. from an area of
high to one of low pressure. The rate of diffusion of a gas across a (tissue)
surface is directly proportional to both the area of the surface and to the
difference in gas pressure between the two sides, but is inversely proportional
to the thickness of the surface. The blood-air barrier in the lungs is very thin
and has a total area (considering both lungs together) of around 50 to 100
square metres; it is therefore structurally perfect for gas exchange. The large
surface area is achieved by wrapping blood capillaries densely and intimately
around the alveoli:
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Responding to Ill Health NURS08046 – Life Science Notes
LadyOfHats (2007) Alveolus diagram
https://commons.wikimedia.org/wiki/File:Alve
olus_diagram.svg
The pressure of O2 in the blood just entering a pulmonary capillary is about
40mm Hg, (5.3kPa) while only 0.3m away in the alveolar air the pressure of
O2 is 100mm Hg (13.3Kpa) therefore O2 rapidly flows down this considerable
pressure gradient into the blood in the pulmonary capillary. Similarly, the
pressure of CO2 in the pulmonary capillary is 44mm Hg (5.9kPa), whilst the
pressure of this gas in the alveolar air is 40mm Hg (5.3kPa) thus CO 2 flows
down its pressure gradient into the air in the alveolar spaces.
If the driving pressure between air and blood is reduced (e.g. at high altitude)
or the blood-gas barrier is thickened (e.g. by fibrosis) or overall lung surface
area is reduced (e.g. emphysema) then diffusion can be impaired, with
possible serious consequences.
Control mechanisms and regulation
Breathing can be automatic or conscious. Normally, we are unaware of
control mechanisms changing our respiratory rate to suit our needs; however,
in many activities, such as playing a musical instrument or singing, breathing
has to be consciously controlled.
As in other systems, the basic principle in the control of respiration is one of
negative feedback, and there are three main elements involved:
1. sensors - gather information
2. control unit (in the brain) – analyses the information from the sensors and
initiates the appropriate response
3. effectors - produce the required change
There are many different sensor systems involved in normal automatic
respiratory control. The most important are sensors that respond to chemicals
(chemoreceptors). The chemoreceptors involved in respiratory control
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Responding to Ill Health NURS08046 – Life Science Notes
respond to changes in O2, CO2 and H+ levels in the blood. The normal partial
pressure values for O2 and CO2 in arterial blood are as follows: O2 –
100mmHg (13.3 kPa); CO2 – 40mmHg.(5.3kPa)
Chemoreceptors in the brain sense changes in pCO2 and H+ concentration in
the cerebrospinal fluid surrounding the brain; those in some of the major
arteries (the aorta and the carotid arteries) detect changes in arterial pO2,
pCO2 and H+ levels. Clearly, increased arterial pCO2 and increased H+ levels
lower pH or decreased arterial pO2 levels will bring about an increased
respiratory effort, whilst the opposite changes in these levels will bring about a
reduction in this effort. It is the pCO2 that is the principal parameter in
determining the activity of the respiratory system on a minute-by-minute basis.
NB high H+ concentration is the same as saying low pH or acidity. Whenever
the blood pH falls respiration increases as in diabetic ketoacidosis or renal
acidosis.
Other sensors include stretch receptors in the lung: these modify the
respiratory process in response to the degree of stretching of the lungs increased stretching causes a reduction in the respiratory rate by increasing
the time taken for expiration, whilst decreased stretching stimulates
inspiratory muscle activity.
The lung also has receptors which lie in airway cells, the nose, nasopharynx,
larynx and trachea which are stimulated by noxious gases, cigarette smoke,
inhaled dusts and cold air. Stimulation of these receptors produces reflex
constriction of the airways - this is thought to be important in asthma.
All these control processes are mediated by the autonomic nervous system.
Voluntary control of respiration is initiated in the cerebral cortex and can override the above automatic controls to some extent, though not completely –
e.g. you cannot stop yourself breathing for any length of time.
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Responding to Ill Health NURS08046 – Life Science Notes
CELLS
(Genetic Inheritance & Cancer)
Revise your knowledge of the cell:
LadyofHats (2006) Animal Cell Structure
http://commons.wikimedia.org/wiki/File:Ani
mal_cell_structure_en.svg
Introduction
Note that the nucleus is a vital cellular structure which contains the genetic
material (DNA). DNA carries information in coded form which enables the
transfer of characteristics from one generation to the next. When the cell
divides, DNA is visible as rod-like structures known as chromosomes.
Each chromosome contains many genes, (think of chromosomes as long
chains of beads, with each bead representing a gene)
Each gene is different from its neighbours and each gene will act as
template to code for a protein (e.g. enzyme, hormone) to be synthesised by
the ribosomes of the cells.
Since there are many thousands of genes making up all of our chromosomes
it therefore follows that there are many thousands of different proteins all with
different functions. The normal development, growth and functioning of the
human body requires that all genes are expressed in the right amounts by the
right cells at the right times.
Chromosomes & Normal Karyotype
The nuclei of all normal human cells (except egg and sperm cells) have 46
chromosomes. The chromosomes exist as homologous pairs (= same pairs),
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Responding to Ill Health NURS08046 – Life Science Notes
one member of each pair is inherited from the mother and the other from the
father. Thus we have two copies of each chromosome. The chromosomes
can be stained and photographed and then arranged with each member of a
homologous pair laid beside its partner to display the karyotype (the sum total
of the different chromosomes we possess).
All normal individuals, male or female, possess 22 pairs of autosomes
(chromosome pairs 1 to 22). Chromosomes in pair 23 are the sex
chromosomes, which among other things; determine the sex of an individual.
Females possess a pair of large sex chromosomes (X chromosomes); males
have one X chromosome and a smaller chromosome (Y chromosome). The
normal male karyotype is described as 46XY and then normal female is
46XX.
The figure below shows a typical karyotype - note homologous chromosomes
are arranged in pairs.
National Cancer Institute (2007) Karyotype_(normal).
https://commons.wikimedia.org/wiki/File:Karyotype_(normal).jpg
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Responding to Ill Health NURS08046 – Life Science Notes
Alleles and Genes
As the nucleus has two copies of each chromosome, it therefore follows that
there are two copies of each gene, one on each of the homologous
chromosomes. One homologous chromosome from each pair is paternal in
origin and the other maternal, therefore one copy of each pair of genes comes
from the mother and the other from the father.
Each chromosome has many different genes at different sites (loci. The
singular is locus) e.g. genes A and B in the figure below. The same site
(locus) on each of the homologous pairs has a version of a particular gene
coding for the same trait (characteristic). Different versions of the same
gene are known as alleles e.g. allele a or A.
e.g. the trait may be eye colour, dimples, freckles etc. One allele may code for
freckles the other allele codes for “clear” skin.
gene
Allele A
UWS Staff (2015)
A
a
B
B
Allele a
Dominant & Recessive Alleles
Some alleles may dominate over others. The
dominant allele is usually represented by a
capital letter and the recessive allele by the
same letter, but lower case.
For example, Ear lobes may be unattached
(fig A) or attached (fig B):
Jomegat (2006) Earlobes_free
The gene coding for unattached earlobes (E)
https://commons.wikimedia.org/wiki/Fil
is dominant. The allele for attached earlobes
e:Earlobes_free_attached.jpg
(e) is recessive.
A person with two copies of the dominant allele (EE) will have unattached
earlobes, a person with two copies of the recessive allele (ee) will have
attached earlobes, a person with one of each (Ee), will have unattached
earlobes because E is dominant.
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Responding to Ill Health NURS08046 – Life Science Notes
Genotype & Phenotype
The genotype refers to the genes present in an individual e.g. EE, Ee and ee
in the example above.
The phenotype describes the appearance of the individual e.g. Phenotype unattached earlobes.
A homozygous individual has a genotype with two copies of the same allele
e.g. ee and EE.
A heterozygous individual has a genotype with two different alleles e.g. Ee.
Cell Division and Reproduction
The only physical links between parents and their children are the gametes –
the male sperm and the female ovum. Sperm and ova are produced by a
type of cell division known as meiosis and have only half of the number of
chromosomes of the parent cell. We say that the gametes are haploid (n)
and the parent’s body (somatic) cells are diploid (2n).
As a result of fertilization a diploid cell (zygote) is formed with 23 pairs of
chromosomes, one member of each pair coming from the sperm and one
from the egg.
The tiny zygote (no larger than a “full stop” on a page) will divide many times
until eventually it becomes a mature individual.
This type of cell division is called mitosis and produces daughter cells with
exactly the same number and kinds of chromosome as the parent cell.
Punnett Square
If the genotypes of the parents are known it is possible to work out the
probability (chance) of having a child with a particular genotype. This can be
done by constructing a Punnett square.
The concept of probability is straightforward- what is the chance (probability)
of tossing a coin and getting tails? This can be expressed as 50% or 0.5 or ½.
Continuing with the example of attached and unattached earlobes
If a father’s genotype is Ee what is his phenotype? …………
Which types of gamete will he produce?.................................
If a mother’s genotype is ee what is her phenotype?..............
Which types of gamete will he produce? =…………
In the Punnett square below- fill in the parental gametes and the genotypes of
the possible children
Mother
Gametes
Father
What is the probability of this couple having a child with attached earlobes?
..............................
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Responding to Ill Health NURS08046 – Life Science Notes
Dominant and Recessive Disorders
In some cases a gene may mutate and no longer properly code for its gene
product. Many mutations are harmful and usually result in some loss of
function. This loss of function may range from minor to fatal.
Mutations
A change in the sequence of the bases of the DNA (mutation) can alter the
template which is used to make the proteins. When new proteins are
synthesised using the ‘faulty’ template they may change their properties e.g.
an enzyme may lose its activity.
Mutations can arise because of:

Errors in the copying process during the replication of DNA as cells
prepare to divide.

environmental factors: such as radiation or certain chemicals
Mutations that occur in

Sex cells can be passed on to future generations

body cells cannot be inherited
Mutations may occur in the sex chromosomes or in any of the 22 pairs of “non
sex” chromosomes (autosomes)
Autosomal Dominant Disorders
The mutation occurs in a dominant allele of a “non-sex” chromosome
heterozygotes have the condition, there is no carrier state as only one allele
is required. Half the children of a sufferer will probably develop the condition
Examples;

Neurofibromatosis – gene located on chromosome 17. Tumour-like
growths on skin (termed café au lait spots) and nervous system. The
symptoms of the disease are variable from mild to severe (i.e. show variable
expressivity). See work book.
Example A man suffering from neurofibromatosis with genotype Nn marries a
woman without the disorder and they plan to have several children.
Father’s genotype - Nn. His phenotype= …………
Different types of gametes produced …………
Mother’s genotype …….. Her phenotype = …………
Types of gamete produced …………
(Fill in the gametes and genotypes of the possible children)
Mother
Gametes
Father
What is the probability of this couple having an affected child? .........................
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Responding to Ill Health NURS08046 – Life Science Notes
Autosomal Recessive Disorders
In these disorders the recessive allele is abnormal. Only individuals who
receive two copies of the abnormal allele will express the abnormal protein
and suffer from the disease. Heterozygous individuals (one copy of
dominant allele and one of recessive) have normal phenotypes but are
carriers of the disorder. See work book.
Examples:
Cystic fibrosis – the most common recessive human disorder affecting about
1 in 2000 births, approximately one person in 22 is a carrier. Gene located on
chromosome 7.
Clinical symptoms are mainly associated with thick viscous mucus secretions
throughout the body, but particularly in the lungs. At a cellular level the
problem is that chloride ions fail to pass through plasma membrane channel
proteins. Normally, after chloride ions have passed through the plasma
membrane, water follows. Lack of water gives rise to thick viscous mucus.
PKU - phenylketonuria occurs once in 5,000 births, and is the most
commonly inherited metabolic disorder to affect nervous system development.
Gene located on chromosome 12.
Affected individuals lack an enzyme phenylalanine hydroxylase which
converts the amino acid phenylalanine to tyrosine. Accumulation of
unmetabolised phenylalanine causes severe mental retardation.
Other recessive conditions include: autism, albinism.
Example: A man and woman, who are both carriers of PKU marry and also
plan to have several children. Complete and answer the following:
Father’s genotype…………
His phenotype =…………
Different types of gametes …………
Mother’s genotype …………
Her phenotype =………….........
Different types of gametes …………
Mother
Gametes
Father
What is the probability of their having?
An affected child ? .........................................................................................
A carrier child ?...............................................................................................
A child who is neither affected nor a carrier ?.................................................
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Responding to Ill Health NURS08046 – Life Science Notes
Sex Linked Disorders
Both X and Y chromosomes carry genes which code for sexual
characteristics, but the X chromosome also carries many genes coding for
other traits.
Alleles on the X chromosome often do not have an equivalent allele on the Y
chromosome (simply because the Y chromosome is so small). Thus a man
(XY) has only one X chromosome and therefore has only one copy of the
alleles found on it. He must therefore express these alleles whether they are
dominant or recessive. On the other hand a woman (XX) has two copies of
the X chromosome and the alleles “behave” in the same way as autosomes
i.e. a woman needs two copies of an X-linked recessive allele to express
it, a man needs only one. An example would be red /green colour blindness.
Example: A man with normal vision marries a carrier woman and they also
plan to have several children.
Father’s genotype…………
His phenotype=…………
Different types of gamete produced …………
Mother’s genotype …………..
Her phenotype…………
Types of gamete produced…………
XC
Y
XC
Xc
Use the Punnet square to work out the chance of a child being
A colour blind boy............................................
A carrier girl ....................................................
Note: with X-linked disorders:
 Men
cannot
be carriers but women can.
Mutations
and
Cancer
 occurs
Many more
women
aremutation,
likely to be
Cancer
when,men
as athan
result
of gene
theaffected
growth by
andthe
division of
disorder.
cells becomes uncontrolled.
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Responding to Ill Health NURS08046 – Life Science Notes
Mutations and Cancer
A mutation is any event that changes genetic structure or sequence of a cell.
Cancer occurs when, as a result of gene mutation, the growth and division of
cells becomes uncontrolled.
It is likely that several mutations are needed over many years for a cancer to
develop from normal tissue, in a process known as carcinogenesis.
Carcinogens (agents which predispose to tumour development) cause
mutations in the genes controlling cell division: These agents may be:
 chemical
 physical (e.g. radiation, ultra violet light)
 viral (NB recent publicity HPV & cervical cancer)
Classification and Behaviour of Tumours
The word tumour (neoplasm) is used to describe a mass of tissue which
grows more rapidly than normal, in an uncoordinated way, and continues to
grow when any initial stimulus is removed.
Tumours may be may be benign or malignant,
A malignant tumour is a cancer.
Tumours are also classified according to their tissue of origin.
 e.g., carcinoma malignant tumour of epithelial tissue
 adenoma – benign tumour of epithelial tissue
This classification can be quite complex
Benign and malignant tumours have very different characteristics –and
these are summarised in the table below.
Benign
Slow growth
Cells well differentiated
(resemble tissue of origin)
Usually encapsulated
No distant spread
(metastases)
Recurrence is rare
Malignant
rapid growth
Cells poorly differentiated
(do not resemble tissue of origin)
Not encapsulated
Spreads (metastases) via:
Lymph. Blood, Body cavities,
Local infiltration
Recurrence is common
Some tissues more affected by metastatic spread than others:
E.g. LUNGS pulmonary circulation
LIVER hepatic portal circulation
BRAIN, KIDNEY, BONE – large blood supplies
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Responding to Ill Health NURS08046 – Life Science Notes
PHARMACOLOGY
Recall from 1st year notes that pharmacology is the study of the interactions
between chemicals (drugs) and biological systems. Generally drugs are given
therapeutically to: prevent, cure or control various disease states (e.g.
antibiotics to treat bacterial infection; insulin to control diabetes) or modify
normal body functions
Also recall that pharmacology can be divided into two parts 1)
pharmacokinetics – this is what the body does to the drugs and 2)
Pharmacodynamics – this is what effect(s) the drugs have on the body.
Pharmacokinetics
Drugs are absorbed, usually into the blood, and distributed into the various
tissues of the body. They may then be excreted unchanged, but usually they
are metabolised (their chemical structure is altered) and then excreted.
Absorption
Absorption describes the process by which drugs enter the body proper and is
affected by many factors such as The chemical nature of the drug. and Route
of administration. Most drugs are taken orally but these are liable to be (partly)
destroyed by the first-pass effect” .
Distribution
After a drug has been absorbed into the body proper it is then dispersed
around the various tissues of the body by the blood. We must ensure that the
drug reaches its target tissue at a sufficient concentration to have the desired
therapeutic effect. A number of factors affect this distribution such as: the
chemical nature of the drug; if drug binds to plasma proteins, the size of drug
molecules and how lipid soluble the drug is.
Metabolism
The body contains a large number of enzymes which are capable of. This
process, known as metabolism, usually (though not always!) terminates a
drug’s action and makes it more water soluble and thus more readily excreted
from the body.
Metabolism refers to changing the chemical structure of the drugs which we
take. This usually reduces action of drug. Drug metabolism can take place in
almost any tissue but is mostly carried out in the liver where the levels of
metabolic enzymes are highest.
Excretion
This is the process whereby a drug and/or its metabolites are eliminated from
the body. Drugs may be excreted by a variety of routes: urine, exhaled gases,
faeces, saliva, sweat, milk.
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Responding to Ill Health NURS08046 – Life Science Notes
Plasma levels, half-life and steady-state levels
The levels (concentration) of a drug in the plasma over time will depend on a
combination of the route of administration (how much enters the blood and
how fast) and rates of metabolism and excretion (how fast the drug is
broken down and removed from the body).
How fast a drug is metabolised and excreted from the body is an extremely
important clinical consideration as it will affect our choice of dose and dosing
schedule (how often the drug is administered). A drug which is quickly
metabolised and excreted will have to be administered at a higher dose and
perhaps more frequently than a drug which is slowly metabolised and
excreted. We therefore need a measure of the speed of removal of a drug
from the plasma - this measure is the half-life.
140
120
UWS Staff (2015)
Plasma Drug Concentration
100
80
60
40
Half-life
20
0
0
20
40
60
80
100
120
140
Time
After a drug has been administered, its concentration in the plasma will rise to
a maximum level and then begin fall as it is metabolised and removed from
the plasma. The half-life of a drug is the time taken for its concentration in the
plasma to fall by half. The shorter a drugs half-life, the more rapidly it is
metabolised and excreted and the shorter is its duration of action in the body.
Different drugs have different half-lives. Drugs which are slowly metabolised
or excreted have long half-lives, whereas drugs which are rapidly
metabolised or excreted have short half-lives. The figure below allows you to
see a comparison of three drugs with differing half-lives. The half-life helps
determine how often (frequency) a drug must be administered.
Drug Dosage Regimes (How do we know how much drug to give and how
often?)
The therapeutic properties of drugs can only be properly achieved if the dose
of drug is correct and the blood levels are maintained within those correct
limits for the duration of the course of treatment.
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Responding to Ill Health NURS08046 – Life Science Notes
Therapeutic Range
It is important to ensure that the amount of drug given produces a plasma
concentration which falls within the correct range to be effective (therapeutic
range). If the plasma concentration is too low the drug may have little or no
effect, conversely if it is too high there may be adverse or toxic effects. E.g. a
single large dose of drug may initially have no effect then may ‘overshoot’
into the toxic range then ‘drop-off’ back into having no effect (see figure
below).
Therapeutic Range
effect of single large dose
Plasma concentration of drug
Toxic
effects
Therapeutic
Range
No effect
0
Drug given
12
Time (hours)
24
UWS Staff (2015)
Repeated Drug Doses
Ideally the plasma concentration of the drug should be maintained between
set limits (i.e. within the therapeutic range). To achieve this, the administration
of the drug must occur at regular intervals. These intervals are influenced by
the half-life of the drug and its therapeutic range (see figure below). Drugs
with a short half-life require frequent administration and long half-life drugs
less frequent (this is why different drugs have to be taken at different
frequencies e.g. two times or 6 times a day etc). Notice that drug
concentration accumulates with repeated doses. As drug molecules
accumulate in the body the plasma concentration eventually ‘levels off’ to
reach a plateau called the Steady-State level (since drug input and
excretion/metabolism are roughly equal). However if dosing frequency is not
great enough then the plateau stage is never achieved.
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Responding to Ill Health NURS08046 – Life Science Notes
Therapeutic Range
effect of single large dose
Plasma concentration of drug
Toxic
effects
With reference to
the graph - which
dosing frequency
is best? Why?
Therapeutic
Range
No effect
0
Drug given
12
Time (hours)
24
UWS Staff (2015)
Some drugs take a relatively long time to reach their steady-state level.
In such cases a larger initial dose may be given (loading dose or bolus)
followed by smaller repeated or continuous doses in order to reach the
steady-state more quickly.
The pharmacokinetics of a drug can be affected by a number of “patientspecific” factors such as age (the very young and the elderly often show
differences in drug metabolism and renal function), genetics (people may
have differences in the enzymes which metabolise drugs) and disease (liver
and kidney problems in particular may affect drug pharmacokinetics). Another
factor which may affect the pharmacokinetics of a drug is that of drug
interactions (more on this later). If someone is taking more than one drug,
they may interfere with each other’s metabolism.
Pharmacodynamics
i.e. what a drug does to the body. This is often referred to as the “mechanism
of action”. Most drugs act by interacting with macromolecules (usually a
protein but may be a nucleic acid) on or inside cells. The macromolecule a
drug interacts with is known as its receptor or target.
An agonist is a drug molecule activates a receptor to induce some change in
activity of the cell or tissue.
An antagonist binds to a receptor but does not activate it, instead it prevents
other agents from activating the receptor and hence are sometimes called
“blockers”.
Recall that most drugs act by one of the following basic mechanisms:
1.
Mimicking or inhibiting a neurotransmitter or hormone e.g., blockers, anti-histamines, oral contraceptives.
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Responding to Ill Health NURS08046 – Life Science Notes
2.
Inhibiting an enzyme e.g., NSAIDs, ACE inhibitors
3.
Interfering with a transport molecule e.g., local anaesthetics, antidepressants, anti-ulcer drugs.
4.
Most antibiotics and anti-cancer drugs interfere with the function of
DNA or RNA either by one of the above mechanisms or by directly interfering
with the DNA or RNA.
We will now look at some details of how drugs work by considering two
classes of drugs: Analgesics and Antibiotics
Analgesia (An- “without”; algesia- “the sensation of pain”)
Analgesics are therefore drugs which relieve pain.
Pain is generated through activation of a specific receptor type called
nociceptors. These nociceptors are found in great abundance in the skin,
blood vessels, joints and areas of the gut but are sparse in other areas of the
body (e.g. there are very little nociceptors present in the brain tissue and
headaches are generated through activation of receptors in blood vessels and
membranes). Pain serves an essential protective function to warn of injury
and minimise damage to the body but excessive or prolonged pain can be
very debilitating.
Nociceptors are activated through chemical (e.g. prostaglandins, histamine,
etc); mechanical (e.g. physical disturbances) or thermal (heat or cold)
means.
Following activation, nociceptors lead to generation of a “pain message” i.e.
the sending of action potential impulses along peripheral pain nerves to the
spinal cord where they synapse with ascending sensory neurones and then
on up to the thalamus in the brain, where there is a synapse with neurones
leading to the sensory cortex in the parietal lobe and sensation is
experienced. Therefore any mechanism or drug that reduces the number of
action potential impulses reaching the sensory cortex will act to reduce pain
sensation.
The body has the ability to reduce pain sensation endogenously through the
release of endorphins, dynorphins and encephalins. These “natural”
painkillers are in fact peptide neurotransmitters produced by the brain which
act to block pain transmission. The circumstances underlying the release of
these agents is not well understood but collectively they are known as the
opioid system and are extremely effective at supressing pain signals from
the peripheral nerves.
Further endogenous means of reducing pain sensation is through a
mechanism called gate control, which suggests that (usually mild-moderate)
pain perception can be reduced by simultaneously activating non-pain
receptors in a way the “closes the gate” to pain sensation. The physiological
processes underlying this are complex but this is a system that can often be
utilised effectively e.g. touch or gentle rubbing of a painful area can ease
the pain by stimulating touch receptors which are also able to block the
passage of the pain signals at synapses. Similar mechanisms are thought to
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Responding to Ill Health NURS08046 – Life Science Notes
underlie TENS machines (transcutaneous electrical nerve stimulation) used
for musculoskeletal or labour pain.
In terms of drugs used to alleviate pain, there are two major pharmacological
groups of analgesics: Opioids, which act centrally (on the central nervous
system to mimic the opioid system) and those classed as non-opioids which
can either act centrally or at the site of tissue damage in the periphery.
Adjuvants are agents which can boost the efficiency of analgesics although
on their own do not necessarily possess any pain relieving action (e.g.
caffeine can promote the action of paracetamol). In terms of clinical pain
management, analgesic use tends to be split into a 3-step ladder that
progresses with the level and persistence of pain. The steps start with nonopioid use (e.g. NSAIDS or paracetamol ± adjuvant) then progresses to weak
opioid use (e.g. codeine ± adjuvant) and finally to strong opioid (e.g.
morphine) ± non-opioid ± adjuvant. This system will be discussed in more
detail by HNM staff.
NSAIDs (non-steroidal anti-inflammatory drugs) and paracetamol
When tissue damage occurs, a rapid non-specific defence mechanism is
triggered- the inflammatory response. The body activates a series of
mechanisms to limit further damage and prevent infection: the tissue swells,
reddens and becomes hot to the touch. The body uses many chemical
messengers to bring about the inflammatory response, one such group of
messengers are the prostaglandins. One of the actions of the prostaglandins
is to make the nociceptors in the damaged area more sensitive.
The process the body uses to make the prostaglandins depends on enzymes
called cyclo-oxygenases or COX. NSAIDs (such as aspirin and ibuprofen)
inhibit these COX enzymes, and so decrease the amount of prostaglandins
which are produced- this reduces the sensitivity of the nociceptors, and so
reduces pain. Paracetamol is also used to treat inflammatory-type pain but
because it has very little actual anti-inflammatory action it is not classed as an
NSAID. NSAIDS prevent nociceptors sending pain impulses but even if pain
impulses are sent the message pathway can be interrupted. The passing of
the message from the peripheral nerves to the spinal cord nerves can be
blocked. This blocking of the signal causes a reduction in the amount of pain
which the brain “feels”- the pain hasn’t gone away, the brain is just less aware
of it. This blocking of the signal in the spinal cord can be done in a number of
ways;
Local anaesthetics (like lidocaine given at the dentist) generally act as
sodium channel blockers, preventing sodium entering neurones, thus blocking
the peripheral action potentials reaching the CNS. Such drugs can also be
used to inhibit large groups of peripheral nerve as they enter the spinal cord
by injecting them in the epidural space around the cord. This type of
administration is useful for preventing pain during childbirth or certain types of
surgery.
Opioid analgesics such as morphine, diamorphine (heroin), pethidine and
codeine mimic the action of the brains peptide opioid neurotransmitters and
so block the pain signal. The original drug of this type was morphine which is
the active chemical in opium (hence the name of the group). In addition to
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Responding to Ill Health NURS08046 – Life Science Notes
being very good analgesics, the opioids have a number of side effects:
euphoria and sedation (both of which can be helpful), confusion, respiratory
depression in overdose, and other side effects such as nausea and
constipation which are caused by the presence of opioid receptors in other
parts of the body. They also have the potential to induce dependence
(addiction) in patients; this effect is more likely with the ‘stronger’ opioids such
as morphine and diamorphine. The opioids are particularly useful during and
after surgery, and in the management of severe chronic pain, especially in
terminal illness. Pethidine and diamorphine are also used during labour. N.B
this is different from epidural anaesthesia described earlier.
Not all drugs described as analgesics act through the mechanisms described
above (e.g. flupirtine, amitriptyline and gabapentin). The actions of such
agents are not described here but serve to highlight just how complicated the
physiological mechanisms underlying pain really are.
Antibiotics
Antibiotics (more accurately referred to as antibacterials) are drugs which are
used to treat bacterial infections. Some of these drugs actually kill the bacteria
(bacteriocidal), whereas others only inhibit the growth of the bacteria
(bacteriostatic). Antiseptics kill bacteria but would usually also kill human
cells if taken internally. Antibiotics have to target bacterial cells where
they differ from human cells also they are not effective against viruses.
There are two major concerns in terms of the use of antibacterial drugs; the
first is specificity- how to ensure that the drug is toxic to the bacteria but as
safe as possible for the patient. The second issue is bacterial resistance,
bacteria are developing the ability to survive drug treatment and as such pose
a grave danger to patients.
There are a large number of antibiotics, with various mechanisms of action;
the diagram below is for illustration and is not intended to be memorised
Kendrick Johnson (2011) Antibiotics Mechanisms of action
https://commons.wikimedia.org/wiki/File:Antibiotics_Mechanisms_of_action.png
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Responding to Ill Health NURS08046 – Life Science Notes
A major group of antibiotics impair cell wall formation in the bacteria (e.g., the
penicillins and the cephalosporins). Animal cells do not have a cell wall, so
these drugs should be very specific for the bacteria- unfortunately this does
not mean they are harmless to humans, many people are allergic to these
drugs. Some bacteria have also become resistant to the penicillins and
cephalosporins, they produce an enzyme (-lactamase) which is able to break
down part of the drug molecule and render it useless.
The remainder of the antibiotics act to inhibit DNA (or RNA) replication or
protein manufacture. These drugs prevent the bacteria dividing and are
therefore mostly bacteriostatic.
The commonest side-effects of antibacterial drug treatment are nausea and
rash.
Drug Interactions (how one drug can affect the action of another drug)
Beneficial Interactions
A ‘cocktail’ of different antibiotics may prevent development of antibiotic
resistant strains. The ‘cocktail’ of cytotoxic drugs in chemotherapeutic
treatment of tumours are more effective at reducing tumour growth. Halothane
is a good anaesthetic but a poor analgesic therefore, during halothane
induced general anaesthesia, analgesics (e.g. opioids or nitrous oxide) may
also be used.
Adverse Interactions
Before administration drugs should not be mixed together (unless otherwise
directed) because the chemical properties of the drugs or other constituents
may interact and change the activity or the physical properties of the drugs
e.g. solubility which in turn could reduce absorption of the drug. After
administration drugs may interact with each other or foodstuffs to produce a
variety of undesirable actions. The potential for interactions is so great that it
is impossible to discuss them in any detail here; however, one example is
given below.
Drug molecules may bind to plasma proteins (mainly albumin). Bound drugs,
such as warfarin (an anti-coagulant), are inactive and it is only when they
are free are they active. The binding of the drug is reversible and as the free
form of the drug is metabolized or eliminated, bound drug is released from the
albumin thus keeping the plasma free (active) drug level relatively constant.
Thus albumin can act as drug reservoir. Administration of another drug, such
as sulphonamides (an antibiotic), to someone who has already taken
warfarin will cause the warfarin to be ‘pushed off’ the albumin thus increasing
the free form of anti-coagulant and as such the clotting ability of the blood
could be enormously compromised resulting in enhanced risk of
haemorrhage.
Sources of Information on Drugs
British National Formulary- www.bnf.org
Patient Information Leaflets, Textbooks
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