Homeostasis

Adrenal Gland Stress control

Corticotrophin releasing hormone Cortisol (CRH) Adrenal Gland Hormones Aldosterone Cortisol Androgens Adrenaline

Adrenocorticotrophic hormone (ACTH) Receptors

Mineralcorticoid Cortex Glucocorticoid or mineralcorticoid Androgen Adrenergic

medulla

Synthesised from cholestrol with 20-22 desmolase rate limiting and 21-hydroxylase---Congenital adrenal hyperplasia. High cortisol secretion before you wake up Mineralcorticoid receptors have equal affinity for aldosterone and cortisol but in alsosterone targeted tissue, an enzyme converts glucocorticoids to inactive form. Functions of glucocorticoids: 1.) Metabolic response to stress mobilisation of fuel breakdown of fat and protein stimulation of gluconeogenesis in liver raised plasma glucose, FA & AA 1.) Anti inflammator Depresses immune response 1.) Developmental maturation of surfactant in lung Cortisol-glucocorticoids used as anti-inflammatory drugs e.g. dethmathasone excess------cushings deficiency------Addison's Mineralcorticoids (Aldosterone) also contribute to stress response.

Adrenal Medulla Sympathetic stimulation ---- medulla secretes: Adrenaline (80%) ; Noradrenaline (20%) Both synthesised from tyrosine Function: intensifies and prolongs the immediate sympathetic response to stress via multiple effects. 1.) Metabolic Mobilisation of fuels gluconeogenesis Breakdown of fat and protein Increase plasma glucose, fatty acids, amino acids 1.) Increase in rate and force of contractility Dilation of blood vessels in skeletal muscles constriction of blood vessels in skin and viscera resultant increase in blood pressure 1.) Respiration Increased breathing rate and dilation of airways Other notes Plasma 3.4 L 8% 300 mOsm Extracellular fluid (13.9L) 33% Total = 42 L Interstitial 10.5 L 25% 300 mOsm Intracellular 28.1 L 67% 300 mOsm

Sodium 150mmol per litre Calcium 5 mmol per litre Potassium 5 mmol per litre pH 7.4 urine production 1.5 L per day ; 50 1200 mOsm Between 80 180 mmHg BP, GFR is fairly consistant -intrinsic myogenic response Angiotensin II receptors more in efferent then afferent Angiotensin II vasoconstrictor Nitric oxide, prostaglandins vasodilators

Clearance of a substance = urine excretion rate of substance ml/min plasma concentration of substance Filtration fraction = GFR = 0.2 Renal plasma flow Renal threshold = 4g per ml of substrate in plasma on 300mg/100ml plasma Tm = 4mg/min Hydrostatic pressure = 10mmHg Oncotic pressure = 30mmHg Net Driving force = 20mmHg 3 stimuli foraldosterone release: 1.) increse in [K] plasma 2.) High Osmolarity (dehydration) reduces aldosterone output 3.) angiotensin II [part of RAAS pathway] produced by decreased BP and decreased flow through macula densa. If [K] plasma > 2mM then aldosterone is released Hyperkalaemia can result in acidosis type B intercalated Hypokalaemia can result in alkalosis type A intercalated

HIS Notes
Population - set of all individuals about whom we want to learn Samples 2.) be representative but do not want it to be pre-determined 3.) use its properties to make inferences about the population Sampling Error in extrapolating to the population from the sample we need to allow for the fact that the sample may not be completely typical. Standard Error 2.) gives a measure of how much a sample mean might vary between random samples of the same size from the same population. 3.) small SE shows that different samples are likely to give similar sample means from a population. 4.) large SE suggests that there might be considerable variation. In this case the results from a single sample may not be very reliable.

SE = population standard deviation square root of sample size Inference Hypothesis testing traditional Confidence intervals - more popular now in the medical literature Specific Problems of inference: Comparison of means 2.) Paired - A paired comparison arises when we have measured the same variable two or more times on the same subjects and want to compare values. 3.) Unpaired with 2 groups -arises when we compare means in 2 or more independent groups. 4.) unpaired with more than 2 groups One way analysis of variance. Assumptions: These tests all make assumptions about the nature of the data. In particular they assume that the data come, approximately at least, from a Normal distribution. We can check that by drawing a histogram Comparison of proportions 2.) chi square test Non-parametric tests 2.) Sometimes the data are very nonnormal and we have to use different methods 3.) Non-parametric methods are less powerful but do not make the same assumptions and can be applied to ordinal data. 4.) Mann-Whitney test is analogous to the independent samples t-test. Relationships between variables 2.) correlation 3.) regression

Hypothesis testing Form 2 hypotheses - null and alternative Null hypothesis H0: no difference, no effect, equality etc. Alternative hypothesis H1: difference, not equal etc. Examine the evidence to see if we can reject H0 P-Value 4.) Choose and calculate a test statistic - a suitable function of data values and look to see what we would expect to get for this if H0 is true. 5.) Suppose H0 is true. 6.) Calculate the P-value. This is the probability of getting a result at least as extreme as that obtained by chance if H0 is true.

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8.) 9.) 10.)

If the P-value is small then such data are improbable if H0 is true, and so we reject H0 . smaller the P-value, the stronger is the evidence against the null hypothesis If it is not small then we do not reject H0 . usual rule is to reject H0 if P-value <0.05 We then say the result is significant at 5%

Type 1 Error Suppose the null hypothesis is actually true Then the significance level is the probability that we reject it incorrectly! This is called a Type I error. So the lower the significance level, the smaller the chance of making such an error. Type 2 Error Suppose the null hypothesis is not true. A Type II error arises if we do not reject the null hypothesis. The probability of this depends on the magnitude of the difference and the sample size (and other factors) Power This is the probability of correctly rejecting the null hypothesis. Power = 1 Type II error So high power is good Confidence Intervals A 95% confidence interval is calculated approximately as: effect size 2 X SE The 2 X SE term measures the uncertainty in the estimate. The SE term (standard error) depends on the underlying variability and the sample size. We can think of the interval as representing the range of values for the true population effect given the data in the sample. a 95% CI will not include 0 if the P-value <0.05, and vice versa. So the decision is the same in each case. If it does not include zero then reject the hypothesis. The advantage of a CI is that it gives an effect size and a measure of the uncertainty. With a large sample it is possible to obtain a very small P-value when the effect size (e.g. difference of means) is very small. Correlation and Regression Correlation measures the strength of the linear association between two variables. The correlation coefficient takes values between -1 and +1.

Confounding This arises when we are interested in an association between an outcome and an explanatory factor but both of these are related to a third factor a confounder.