User:Scienza/documents/MacPee and Haemorrhaging

The physiological effects of haemorrhaging… Involving the cardiovascular and urinary system.

Introduction
In this investigation, the focus will be mostly on the cardiovascular and urinary systems.

What is haemorrhaging?

Haemorrhaging can be described as sudden rushes of blood from blood vessels either internally or externally. An internal haemorrhage is not entirely easy to detect apart from the patient displaying various symptoms associated with the condition. This is purely because, it is within the body. There may be added complications as a result of this such as inducing immunological responses and increased interstitial pressure.

How does it affect us physiologically in specific, the cardiovascular and urinary systems?

In justifying the physiological effects relating to a haemorrhage, it is fair to say that haemorrhaging leads to hypovolemic shock. This means that the blood volume has dropped severely. This leads to other physiological problems in the cardiovascular system and the renal system in this investigation involving changes in haemodynamics and renal physiology. Most path ways that enable the homoeostasis to return to normal include the endocrine system and the neurological system.

What is MacPee?

The physiological properties can be somewhat simulated by a computational model developed by a C. J Dickinson. This simulation program (MacPee) being used in this investigation is one of a number of the MacMaster series of programs developed by Dickinson and his colleagues. The advantages of MacPee over the other programs include functions of the cardiovascular, the urinary system and even the digestive system that can all be combined in one model as opposed to the others which generally concentrate on just one system.

Materials and Methods
In this investigation, a simulated individual has lost 2 litres of blood (2,000mL).

A loss of blood like this is can be identified as a major haemorrhage.

This simulated individual shall be hereafter known as the subject.

The subject was tested at 6 a.m. each day for six days.

Be aware that the first set of values for day 1 will appear normal. This is solely because they are normal due to the fact that the event of haemorrhaging occurred after this time. Each successive data point shows the effects of the haemorrhage on day 1.

The controlled condition which is affected is the blood volume, therefore the investigation will be about how the body utilises its resources to regain homeostasis by restoring the blood volume back to normal.

Figure 1 Screenshot of article explaining MacPee

SOURCE: American Physiological Society

The above figure indicates the standard functions of MacPee.

See that [4] INSPECT causes this program to create a list of values. The word ‘print’ refers to old computer commands whereby, it displays the data on screen.

MacPee yields various useful data values relating to the physiology of both systems. Of course, other systems are intrinsically linked to the physiologies being examined.

Figure 2 Model flow diagram

SOURCE: University College London (UCL)

Calculations for haemodynamics

MAP = BP Diastol + 1/3(BP Syst – BP Diastol), where MAP is the mean arterial pressure. This pressure is closer to the diastolic blood pressure than the systolic blood pressure in the aorta.

The mean arterial pressure can also be calculated from the cardiac output (CO) and the systemic vascular resistance (SVR) as follows:

MAP = CO x SVR

CO = HR x SV, where SV is the stroke volume. This means that the heart rate is directly proportional to the cardiac output.

Results
Below is a table of values with all the data including; the parameters; their units; and the data points taken at 6 a.m. each day.

Table 1 Data collected from ‘INSPECT’ screen of subject in MacPee.

Normal and Abnormal Physiological Parameters

1748.0

1659.0

1748.0

1498.0

1748.0

1443.0

1748.0

1560.0

Fluid out

mL/day

1330.0

1330.0

1330.0

181.0

1330.0

191.0

1330.0

238.0

1330.0

461.0

1330.0

938.0

Na urine

mmol/L

105.0

105.0

105.0

32.0

105.0

0.0

105.0

0.0

105.0

0.0

105.0

4.0

K urine

mmol/L

48.0

48.0

48.0

223.0

48.0

300.0

48.0

300.0

48.0

237.0

48.0

96.0

BP Syst.

mmHg

123.0

123.0

123.0

93.0

123.0

100.0

123.0

104.0

123.0

107.0

123.0

110.0

BP Diastol.

mmHg

77.0

77.0

77.0

62.0

77.0

65.0

77.0

67.0

77.0

68.0

77.0

70.0

BP mean.

mmHg

93.0

93.0

93.0

72.7

93.0

77.4

93.0

79.9

93.0

81.8

93.0

83.7

CO

L/min

5.0

5.0

5.0

3.3

5.0

4.0

5.0

4.5

5.0

4.7

5.0

5.0

C. Contract.

(L/min)/(mmHg)

1.4

1.4

1.4

2.0

1.4

1.7

1.4

1.6

1.4

1.6

1.4

1.5

Art. Resist.

mmHg/L/min

16.4

16.4

16.4

19.6

16.4

17.0

16.4

15.5

16.4

14.8

16.4

14.4

Symp Act.

Arb. Units

0.9

0.9

0.9

2.4

0.9

1.9

0.9

1.6

0.9

1.4

0.9

1.2

GFR

mL/min

112.0

112.0

112.0

54.0

112.0

2.0

112.0

85.0

112.0

92.0

112.0

104.0

HR

Bpm

75.0

75.0

75.0

87.0

75.0

86.0

75.0

85.0

75.0

86.0

75.0

82.0

Hb

g/dL

15.0

15.0

15.0

12.0

15.0

10.7

15.0

9.8

15.0

9.4

15.0

9.1

PCV

%

46.0

46.0

46.0

36.0

46.0

32.0

46.0

30.0

46.0

28.0

46.0

28.0

Renin

Ng/mL/hr

1.4

1.4

1.4

11.6

1.4

8.9

1.4

7.0

1.4

5.1

1.4

3.1

Aldosterone

Ng/dL

12.5

12.5

12.5

63.0

12.5

53.0

12.5

45.2

12.5

33.3

12.5

11.8

AVP

pmol/L

0.8

0.8

0.8

1.0

0.8

0.5

0.8

0.3

0.8

0.3

0.8

0.6

Key: Fluid in as absorbed from the GI tract; Fluid out as secreted by the kidneys; Na urine as in the volume of sodium secreted into the urine; K urine as in the volume of potassium secreted into the urine; BP Syst is the systolic (ventricular contraction) blood pressure in the heart; BP Diastol is the diastolic (ventricular relaxation) blood pressure in the heart; BP mean is the mean arterial pressure (MAP) and can be calculated from the previous two values; CO is the cardiac output; C. Contract. is the cardiac contractility; Art. Resist. is the renal arterial resistance; Symp. Act. is the sympathetic activity; GFR is the glomerular filtration rate; HR is the hear rate; Hb is the amount haemoglobin in the blood; PCV is the haemocrit; Renin is the amount of renin secreted per hour into the blood from the juxtaglomerular cells; Aldosterone is the amount of the hormone, aldosterone secreted into the blood by the adrenal cortex; and AVP is the amount of arginine vasopressin secreted into the blood from the posterior pituitary.

Note that in all the following graphs, the horizontal (x) axis will represent the time period as in the number of days for the six data points, and the vertical (y) axis will represent the variable data accumulated over that time period. Lines are colour coded green and red on more or less all the graphs displayed. These indicate the normal and abnormal data points.

Figure 3 Fluids in and out for both physiologies

The abnormal and normal physiological values for both fluids in and fluids out have both been incorporated into one graph to show the comparative changes over the six day period.

Note that the first values are normal because the haemorrhage occurred after the data point was taken.

Values for fluid intake are the higher values than those going out.

Figure 4 Blood pressures in the heart

The dashed line indicates the mean arterial pressure.

The upper values indicate the systolic blood pressure.

The lower values indicate the diastolic blood pressure.

Again, the normal and the abnormal blood pressures are indicated by green and red, respectively.

As is evident in this graph, the values for ventricular contraction are higher than for those for ventricular relaxation. This suggests that the ventricles have more pressure when ejecting blood as opposed to when they are filling with flood.

The end-diastolic volume (EDV) and the end-systolic volume (ESV) affect the diastolic blood pressure and the systolic blood pressure, respectively.

These increasing or decreasing volumes cause the pressures in the heart chambers to rise or fall. The rise and fall of pressure controls the four valves. When the volume in the ventricles reaches maximum, the pressure is greater than that of the aorta or pulmonary artery. This causes the semilunar (SL) valves to open. Once these valves open, the blood volume decreases due ventricular contraction causing the ejection of blood from each ventricle. The resultant decrease in blood pressure causes backflow of blood towards the ventricle which shuts off the SL valves. Due to the pressure in the ventricles has decreasing to lower than the pressure in the atriums, the atrioventricular valves open allowing the ventricles to fill with flood. These AV valves are closed again once the pressure becomes greater than in the atriums.

Figure 5 Normal and abnormal haemocrit values

The normal physiological ranges for adults in relation to the haemocrit (percentage of total blood volume occupied by red blood cells) are; from 40 to 54% in males with an average of 47%; and from 38 to 46% in females with an average of 42%.

As is evident, females generally have a lower haemocrit when compared to males. The subject appears to either just below average for males or at the higher value for females. The assumption would be that the subject is male because this value (46%) is indicated as the normal physiology.

The abnormal values above indicate that the number of RBCs (red blood cells) decreases gradually then plateaus in relation to the normal values.

Figure 6 Heart rate and cardiac output together

In this graph, both the values for HR and CO begin to return to normal. The cardiac output in fact does return to normal (5.0L/min) on the sixth day.

The heart rate increases rapidly at first before reaching a relatively constant value of about 86.0 bpm. This then decreases as it begins to return to normal.

On the other hand, the cardiac output decreases and then increases again back to its normal physiological value. According the equation above in materials and methods, the cardiac output should increase as the heart rate increases. This however is not shown in the graph.

The vertical axis is identified as ‘mixed units’ because they are not the same for heart rate and cardiac output. The units for heart rate are bpm (beats per minute), where as the units for cardiac output are L/min (litres per minute). To calculate stroke volume, the cardiac output (L/min) is divided by the heart rate (beats/min) to produce units as L/beat.

SV = CO/HR

Figure 7 Renin and aldosterone levels


 * The units for; renin are ng/mL/hr, which is nanograms (10-9 g) per millilitre (10-3 L) per hour; and aldosterone are ng/dL, which is nanograms (10-9 g) per decilitre (10-1 L).

The upper values are for aldosterone and the lower values are for renin.

To compare the values of renin to aldosterone, as far as the units are concerned there is a difference of 102. Therefore, the amount of grams per decilitre would be 10-7 g.

This can be rewritten as 10-7 g per decilitre of renin compared to the 10-9 g per decilitre of aldosterone.

Figure 8 Sodium and potassium in urine

In this graph, it is evident that as the amount of sodium in the urine decreases, the amount of potassium in the urine increases. These values then begin their slopes back toward the normal range. In other terms, the amount of sodium in the blood increases and the amount of potassium in the blood decreases.

Discussion
It is important to acknowledge that some values in Table 1 are of a direct effect of a change to the controlled condition whereas others are triggered by neurological or endocrinological responses to changes in homeostasis. This means either signals from the brain or spinal cord initiate effectors or chemicals secreted from glands initiate effectors.

4.1 Fluids in and out

The rates of fluid that are taken, both in and out, decrease due to the decreased blood volume. This is because blood is flowing slower through the kidney and gastrointestinal tract. Remembering that the kidneys take the fluids out in the form of urea and the gastrointestinal tract takes fluid in as water previously metabolised by the digestive system, means that these two systems have an effect on blood volume. Figure 3 indicates a definite fall which is greater for fluid out than for fluid in. Both values finally appear to be reaching a normal level. If more data points were available, the expectation would be to see homeostasis restored thus the values would reach the same for those indicated by the green line. It is useful to include both sets in one graph because it allows a relative comparison.  4.2 Blood pressures

Blood pressure in the systole decreases due to the decreased blood volume as does the blood pressure in the diastole due to the same reason. The values in Figure 4 affect the mean arterial pressure, which can be calculated from both the systolic and diastolic blood pressures. Blood volume is directly proportional to the blood pressure. Upon the increase of blood volume, the blood pressure increases.

4.3 Haemocrit

The haemocrit is the percentage of red blood cells in the blood. See Figure 5.

A severe decrease in blood volume essentially means that the number of red blood cells decreases. The graph above supports this.

Blood is lost from the body through haemorrhaging. This blood volume contained a large amount of red blood cells (erythrocytes). This means that the number of these cells decreases. The normal physiological value for haemocrit only returns when the body increases production of these cells. This takes time hence the plateau.

The expectation would be that if the data values continued for few more days, the number would begin to rise.

4.4 Heart rate and cardiac output

The heart rate increases due to signals from the brain, specifically the cardiovascular centre of the medulla oblongata located within the brain stem, as a result of signals sent to this centre from baroreceptors in the arch of the aorta and the carotid sinus. These two detect changes in blood pressure due to the reduction of blood volume.

The cardiac output changes as result of the stroke volume and heart rate. In Figure 6, the values for this however appear to be contrary because they in fact decrease. The venous return decreases along with the cardiac output as a result of reduced blood volume.

Heart rate increases because of increased sympathetic impulses (sympathetic activity). The increased heart rate and decreased cardiac output both contribute towards a weak and rapid pulse.

The reason why the values for the heart rate and the cardiac output do not fit into the equation or for that matter the graph, by this I mean the inverse proportionality which is evident, is because the values for cardiac output reflect the initial changes in normal physiology whereas the values for heart rate are as a result of signals from the cardiovascular centre in the medulla oblongata within brain stem. This is the sympathetic activity, which is a response to a disruption in homeostasis.

4.5 Chemical signals

There is an increased amount of renin secreted from kidneys as a physiological response from the endocrine system because a decrease in blood pressure affects juxtaglomerular cells. Within the first day of the haemorrhage, the renin levels significantly increased. Subsequent days show a gradual reduction in renin secretion. The prediction would be that the level of renin returns to normal. There are no values to show this, however with reference to the values in Figure 7, it would appear most probable.

Renin helps angiotensinogen, which is secreted by the liver, to produce more angiotensin I (one), which is converted by an enzyme in the lungs called ACE (Angiotensin Converting Enzyme) to angiotensin II (two). This increase in angiotensin II causes an increase in aldosterone secreted from the adrenal cortex. The relationship between renin and aldosterone is of direct proportion. This means that, as renin increases so does aldosterone.

Just to note that angiotensin come from the fact ‘angio-’ means blood vessel and ‘-tensin’ means to constrict. Together, they mean to constrict blood vessels hence the resulting vasoconstriction.

This increase in blood pressure is also due to vasoconstriction in the arterioles stimulated by angiotensin II. This vasoconstriction causes an increase in systemic vascular resistance (SVP) and together with an increased cardiac output (CO) this increases the mean arterial pressure (MAP).

4.6 Conservation of sodium and water

This initial rise and fall for potassium and sodium in the urine, respectively, is due to the initial loss of blood volume. This is shown in Figure 8.

Due to the increased amount of aldosterone liberated into the blood, the kidneys work to conserve more sodium and water. This is achieved by facultative reabsorption from the distal convoluted tubule in each nephron. In addition to that, the kidneys secrete more potassium and hydrogen ions into the urine. This means that the sodium levels in urine decrease and potassium levels in urine increase. This in turn causes blood volume and blood pressure to increase allowing both to regain homeostasis. The subject will excrete urine that is more concentrated and less acidic. More concentrated due to increased water reabsorption and less acidic because of the amount of hydrogen ions (H+) has increased. Due to the decrease in hydrogen ions in the blood, the blood becomes more acidic. This may cause acidosis (acid condition). Through the depression of synaptic transmission, the central nervous system (CNS) may be depressed. If this continues, the subject could fall into a coma and eve die.