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AA Radius On Glomerular Filtration Biology Essay

Introduction

The renal system consists of the kidneys, ureters, bladder and the urethra. The two principle functions of this system are the elimination and excretion of organic and metabolic waste from the body and the maintenance of homeostasis by the regulation of water balance, electrolyte levels, pH of the blood and the long term regulation of blood pressure. The nephron is the functional unit of the kidney. It is divided into different sections, each part having a specific function. Collectively they are responsible for urine formation.

Blood flows into the kidneys through the renal artery which then branches into different arteries and finally the afferent arteriole (AA) which gives rise to the glomerulus. The glomerulus, afferent and efferent arterioles being arranged in series are in concert with each other and their dynamics are closely interconnected (Ren et al). Blood enters these permeable capillaries through AA and exits through the efferent arteriole (EA). The difference in the radius of AA and EA creates the hydrostatic pressure in the glomerular capillary (PH) needed to drive filtration of the plasma in the nephron. PH is very high ~ 55 mmHg because it is upstream from EA (Bersten and Holt). Changes in both pressure and blood flow take place in the same direction. The colloid osmotic pressure ( caused by plasma protein, and the capsular hydrostatic pressure (Pfluid) are the two starling forces opposing PH. The glomerular filtration rate (GFR) is the volume of the plasma filtered from the glomerulus into the Bowman’s capsule. Bowman’s space oncotic pressure (B) was ignored as filtration of most proteins is prohibited owing to their size and charge. The net filtration pressure (NFP) being the pressure forcing substances out of the glomerulus. “The important determinants of GFR are to introduce the Starling equation and to focus on the constituents of this equation.” (Karlsen et al.)

GFR = Kf x NFP

NFP= (PH – Pfluid –  + B)

Kf is the glomerular capillary filtration barrier (filtration coefficient).

The experimental aim of this study was to examine glomerular dynamics under conditions in which efferent diameter and pressure remain unchanged while selectively varying the afferent diameter.

Null Hypothesis (Ho): There is no significant difference in the mean change in GFR, GP, and UVF upon increasing AA radius

Alternate Hypothesis (HA): There is a significant difference in the mean change in GFR, GP, and UVF upon increasing AA radius.

Method:

This experiment related to the investigation of the effects of a varying AA radius on glomerular filtration and was conducted as a computer simulation. The experiment simulated the movement of blood through AA into the glomerulus and urine filtered from it was collected into a collecting duct. The blood was then destined to leave the glomerulus via EA. (Figure 1). Unfiltered blood flowed from “source beaker” to a group of tubes for ultrafiltration. This blood then flowed into the “drain beaker”, while urine flowed into a separate beaker.

Figure 1. Simulating Glomerular Filtration

Initially the radius of AA was set at 0.50 mm, while EA radius which was required to remain constant throughout the experiment was set at 0.45 mm. The incoming blood accumulated in a beaker on the left at a pressure of 90 mmHg. The experiment was then run through. The data gained for GFR, glomerular pressure (GP) and urine volume filtrate (UVF) at this stage were recorded and served as a baseline for the experiment. Once the source beaker had been refilled, AA radius was raised in increments of 0.05 mm to a maximum of 0.60 mm with data being recorded after each progression. The AA radius was then lowered to 0.30 mm while all other variables remained unchanged and the data recorded. As a final part of the experiment AA radius was raised to 0.35 mm and data tabulated.

Results:

The results were analysed in accordance to the raw data and are shown in Appendix 2.

Table one shows sample size (n), mean GFR (ml/L) and standard deviations at different AA radii. The mean GFR and standard deviation for radii of 0.30 mm, 0.35 mm, 0.50 mm, 0.55 mm and 0.60 mm were 0.00, 14.24, 124.8, 172.67, 221.73 and 0.00, 0.66, 0.99, 1.27 and 0.90 respectively.

Table 1: Sample size, mean GFR and standard deviations for varying AA radii

Afferent arteriole radius (mm)

Sample size (n)

Mean glomerular filtration rate (ml/L)

Standard deviation

0.30

10

0.00

0.00

0.35

10

14.24

0.66

0.50

10

124.80

0.99

0.55

10

172.67

1.27

0.60

10

221.73

0.90

Figure two illustrates the mean GFR (ml/L) for varying AA radii; the standard deviations are also included. The mean GFR (ml/L) and standard deviation for radii of 0.30 mm, 0.35 mm, 0.50 mm, 0.55 mm and 0.60 mm were 0.00, 14.24, 124.80, 172.67, 221.73 and 0.00, 0.656, 0.989, 1.27 and 0.902 respectively.

Figure 2: Effect of changing AA radii on mean GFR

Table two shows sample size (n), mean GP (mmHg) and standard deviations at different AA radii. The mean pressure and standard deviation for radii of 0.30 mm, 0.35 mm, 0.50 mm, 0.55 mm and 0.60 mm were 44.37, 46.46, 55.37, 58.81, 62.60 and 0.740, 0.356, 0.584, 0.586, 0.681 respectively.

Table 2: Sample size, mean GP and standard deviations of differing AA radii

Afferent arteriole radius (mm)

Sample size (n)

Mean Glomerular Pressure (mmHg)

Standard deviation

0.30

10

44.37

0.74

0.35

10

46.46

0.36

0.50

10

55.37

0.58

0.55

10

58.81

0.59

0.60

10

62.60

0.68

Figure three illustrates the mean GP (mmHg) for varying AA radii; the standard deviations are also included. The mean GP and standard deviation for AA radii of 0.30 mm, 0.35 mm, 0.50 mm, 0.55 mm and 0.60 mm were 44.3, 46.46, 55.37, 58.81 62.60 and 0.74, 0.36, 0.58, 0.59, 0.68 respectively.

Figure 3: Effect of changing AA radii on average GP

Table three shows sample size (n), mean UVF (mL) and standard deviations at different AA radii. The mean UVF and standard deviation for AA radii of 0.30 mm, 0.35 mm, 0.50 mm, 0.55 mm and 0.60 mm were 0.00, 76.28, 201.41, 212.54, 220.85 and 0, 0.647, 1.68, 1.19 and 1.33 respectively.

Table 3: Sample size, mean UVF and standard deviations of differing AA radii

Afferent arteriole radius (mm)

Sample size (n)

Mean Urine Volume (ml)

Standard deviation

0.30

10

0.00

0.00

0.35

10

76.28

0.65

0.50

10

201.41

1.68

0.55

10

212.54

1.19

0.60

10

220.85

1.33

Figure four illustrates the mean UVF (mL) at differing AA radii; the standard deviations are also included. The mean UVF and standard deviation for AA radii of 0.30 mm, 0.35 mm, 0.50 mm, 0.55 mm and 0.60 mm were 0.00, 76.28, 201.41, 212.54, 220.85 and 0, 0.65, 1.68, 1.19 and 1.33 respectively.

Figure 4: Effect of changing AA radii on mean UVF

Table four shows the t-test comparison between 0.50 mm and 0.55 mm AA radii subset in relation to GFR, GP and UVF. The p-two tail values for GFR, GP and UVF were 1.56025E-24, 1.08843E-11 and 1.13786E-10 respectively.

Table 4: t-test comparison between 0.50 mm and 0.55 mm AA radii on GFR, GP and UVF

T-Tests:

P(T<=t) two-tail

Glomerular filtration rate

1.56025E-24

Glomerular pressure

1.13786E-10

Urine volume

1.08843E-11

Discussion:

This study demonstrated that with EA radius fixed at the mean basal value, the increase in AA radius from the baseline to 0.55 mm resulted in a significant increase in both renal blood flow (RBF) and PH. As a consequence there was a corresponding increase in GFR, GP and UVF to this alteration in AA radius. Our experimental results concurred with the findings of Rosivall and Peti-Peterdi that AA was directly involved in the regulation of PH and filtration and with those of Navar and Yilin et al. that gradual increments in AA radii were correlated with changes in GFR, GP and UVF levels. Comparisons between baseline and these components of interaction led to support the alternative Hypothesis (HA). Tabulated results are given as mean ± standard error. To assess the significance of differences in mean values, two-tailed statistical t-tests were used. In all cases, differences between means were judged significant when p < 0.05. (n = 10) (Refer to appendices 1, 2 & 3).

The model of Deen et al. together with RBF, PH and  were used to calculate values of GFR. The fall in resistance upstream reduced the rate of rise in  coupled with an increase in renal blood flowing into the glomerulus. This translated into an increase in both PH and GFR thereby causing an increase in urine volume formation. The main driving force affecting the filtration rate was PH whilst both  and Pfluid were the opposing forces. In order to favour filtration NFP had to be positive whereas once AA radius was lowered to 0.30 mm, filtration ceased abruptly, owing to NFP having dropped to below zero. (Table 6)

GFR = Kf x (PH – Pfluid – )

In contrast, constriction of AA without other changes lead to effects opposite to those described above which reduced both downstream flow as well as PH. This in turn yielded lower levels of GFR, GP and UVF (Ren et al). Urine volume is determined by GFR, the amount reabsorbed and amount secreted along the nephron.

A clinical correlation to such a situation would be when patients with renal stones or prostatic enlargement may present with profound reductions in GFR. Renal function in such cases can often be restored through removal of the obstructing lesion.

Although the experiment is fairly accurate, and the results obtained coincided with those of previous studies, there were some limitations however. Firstly, the results and conclusion have been drawn based on a limited range of data and a relatively small sample size. This can be resolved by extending the data range and through a larger sample size. This in turn will effectively minimise errors and enable us to explore the auto regulation process. Secondly, simulated in vitro studies have limitations in the sense that the physiological relevance of different models is not certain and may be confounded by changes in renal perfusion pressure and the performance of different hormones. It is possible that use of a higher level program could have enabled us to explore this avenue.

Conclusion:

In conclusion this study confirmed that a gradual increase in AA radius at fixed EA radius, produced an increased outflow of urine through elevated glomerular pressure and urine volume filtration rates and vice versa.


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