Biological systems, overview

1. Biological systems, overview Neil Pendleton University of Manchester

2. Human biological systems

3. Biomarkers in panel surveys: outline of session • Provide background to the frequently available biomarkers in panel surveys (see ICLS handbook common survey measurements 2nd edition 2016) • The aim to give deeper understanding of practicalities of measurement and how to use them • Divided into 2 parts: first with on the physical/physiological measures; second on the ‘fluid based’ biomarkers examples bloodor saliva • In break between sessions Q&A and revisit any of the breadth of measures in first lecture students

4. Anthropometry

5. Anthropometry • A branch of anthropology that involves the quantitative measurement of the human body • Portable, inexpensive (equipment) and non-invasive assessment of size, proportion and composition of the human body • Historical perspective including da Vinci and Galton

6. Adult anthropometric parameters Basic measures Derived measures Height (length) Weight (mass) Waist and hip circumference Mid upper arm circumference Skin fold thickness Triceps, Biceps, Subscapular and Supra-iliac BMI Waist hip ratio

7. Body Mass Index ranges and co-morbidity risk WHO and International Obesity Task Force

8. Waist-to-Hip Circumference Ratio (WHR) • Indicator of distribution of subcutaneous adipose tissue • CHD risk linked to abdominal fat • Gender and racial variation • Women WHR 0.85-1.7 (high risk) <0.85 (low risk) • Men 0.95-1.9 (high risk) <0.95 (low risk) • Asians increased metabolic risk lower WHR

9. Mid upper arm circumference • Also called mid arm circumference • Used as measure of nutritional status in adults and children • Evidence can be used to estimate weight

10. Triceps skin fold thickness and derived measures Triceps skin fold thickness Derived measures Measure of subcutaneous fat Correlates with percentage and total body fat Lean adults 6-12 mm Obese adults 40-50 Mid upper arm area (MUAA) Mid upper arm muscle circumference (MUAMC) and area (MUAMA) including corrected Mid upper arm fat area (MUAFA) = MUAA-MUAMA Arm fat index (AFI)=100x(MUAFA/MUAA)

11. Child anthropology • These used to examine values with addition of age related growth patterns (Growth Velocity Charts) • Some measures are more challenging in babies/infants with different equipment • Unlike adults some are age dependent

12. Weight

13. Height • Expected progress over first 12 years life • Growth is non linear • Weech’s formula • Length or height (cms)=age in yearsx6+77

14. Head circumference • Brain growth is 70% foetal; 15% during infancy; 10% pre school years • Routinely collected up to 5 years • Twelve centimetres growth in first year

15. Chest circumference • Measured nipple level mid inspiration • Head circumference bigger than chest circumference by 3 cms in: pre terms; small for dates child; hydrocephalus; malnourished child • At birth head circumference > chest by up to 3 cms • Nine months – one year head circumference=chest • Beyond 1 year chest growth overtakes head

16. Body composition

17. Bio impendence

18. X-ray absorption and DEXA • Principle of x-ray attenuation • Bone higher attenuation than soft tissue

19. DEXA • Use 3 compartment model • Define bone area • Use 2 energies to calculate bone mass • Calculate fat using area outside bone with 2 energies • Use local uniform composition over bone region to calculate whole soft tissue region • This permits estimation lean mass • Examine bone, lean and fat masses for sub regions

20. Cardiovascular and Respiratory measures

21. Cardiovascular measures

22. Cardiovascular measures • Common addition to human panel surveys • Arterial blood pressure • Electrocardiogram • Heart rate variability • Arterial (carotid) intimal thickness

23. Arterial blood pressure • Understand the concept of mean blood pressure, systolic, diastolic, and pulse pressure and mean blood pressure. • Understand normal variations in arterial blood pressure. • Understand the relationship between cardiac output blood pressure and total peripheral resistance. • Understand factors determining blood pressure. • Regulation of arterial blood pressure

24. Arterial blood pressure • Systolic BP=ABP during myocardial contraction • Diastolic BP=ABP during myocardial relaxation • Pulse pressure PP=systolic-diastolic ABP • Mean ABP=diastolic+PP/3 representing all vessel pressure • Cardiac output CO=Heart rate HR x stroke volume SV • ABP=CO x Total Peripheral Resistance TPR • ABP=HRxSVxTPR

25. Arterial blood pressure regulation • Variation by • Age • Gender • Body composition • Emotions • Exercise • Meals • Sleep • Gravity • Mechanisms • Neural: Baroreceptor,; Chemoreceptor; Brain ischemic response • Hormonal: catecholamine; renin-angiotensin-aldosterone system; vasopressin • Renal; body fluid volume regulation • Red rapid; purple intermediate; blue long term

26. Courtesy Dr M Ababnah

27. Hypertension Implementing NICE guidance 2nd Edition March 2013 NICE clinical guideline 127

28. Background • High Blood Pressure: • Major risk factor for stroke, myocardial infarction, heart failure, chronic kidney disease, cognitive decline and premature death. • Untreated hypertension can cause vascular and renal damage leading to a treatment-resistant state. • Each 2 mmHg rise in systolic blood pressure associated with increased risk of mortality: • 7% from heart disease • 10% from stroke.

29. Epidemiology • Hypertension is common in the UK population. • Prevalence influenced by age and lifestyle factors. • 25% of the adult population in the UK have hypertension. • 50% of those over 60 years have hypertension. • With an ageing population, the prevalence of hypertension and requirement for treatment will continue to increase.

30. Definitions • Stage 1 hypertension: • Clinic blood pressure (BP) is 140/90 mmHg or higher and • ABPM or HBPM average is 135/85 mmHg or higher. • Stage 2 hypertension: • Clinic BP 160/100 mmHg is or higher and • ABPM or HBPM daytime average is 150/95 mmHg or higher. • Severe hypertension: • Clinic BP is 180 mmHg or higher or • Clinic diastolic BP is 110 mmHg or higher.

31. Monitoring drug treatment (2) For people identified as having a ‘white-coat effect’ consider ABPM or HBPM as an adjunct to clinic blood pressure measurements to monitor response to treatment. Aim for ABPM/HBPM target average of: • below 135/85 mmHg in people aged under 80 • below 145/85 mmHg in people aged 80 and over. • White-coat effect: a discrepancy of more than 20/10 mmHg between clinic and average daytime ABPM or average HBPM blood pressure measurements at the time of diagnosis.

32. Courtesy Prof El-Masry

34. Electrocardiogram

35. Electrocardiogram • Measure of the electrical activity coordinating cardiac cycle across the 4 chambers • 1924 - the noble prize for physiology or medicine is given to William Einthoven for his work on ECG • Cardiac systole ventricular contraction=depolarization • Cardiac diastole ventricular relaxation=repolarization (?atrial systole)

36. Electrocardiogram • P wave= contraction of atria depolarisation • QRS complex=ventricular depolarisation • T wave=ventricular repolarisation • ECG trace is collection of complexes over time so rhythm and rate can be observed Diastole Systole Diastole

37. Normal sinus rhythm • Rhythm=regular • Rate=60-100 bpm • QRS duration<0.1sec • P wave=0.12-0.25 • P-R interval=0.12-0.20 • QT interval<0.38sec

38. Electrocardiogram • Determined by primary pathologies of the heart such as cardiovascular disease • Also affected by external factors such as exercise, emotional stress, pain, temperature, respiratory, hormonal factors, medicines and substance use • Consider operator affects also such as lead positioning, body position

39. Heart Rate Variability

40. Heart Rate Variability (HRV) • HRV is index of autonomic function • Decrease in HRV increases risk arrhythmia and sudden cardiac death • Associated with: depression; diabetes mellitus; heart failure; hypertension

41. Heart Rate Variability (HRV) • HRV criterion is normal R-R interval • Factors influencing data accuracy • Quality of ECG wave forms • Quality of data subjects vary • Quantity data (day ~0.85M beats) • Influenced by age, gender, disease status and medicines cf. ECG

42. Heart Rate Variability (HRV) Courtesy of Dr E Karey SBNN=para+sympathetic+hormonal system SDANN/SDNNIDX=para+sympathetic rMSSD=parasympathetic

43. Methods of cleaning data HRV Courtesy of Dr E Karey

44. Arterial Carotid Artery Intima Medial Thickness

45. Arterial Carotid Artery Intimal Medial Thickness • Arteries througout the body can be examined by ultrasound • Allows visualisation and measurement of the lumen and the wall structure • Carotid artery often used to represent systemic and cerebral circulation • Identify arterial disease especially atheroma deposition • Varies by gender, age, ethnicity, BMI, lipid levels hypertension • Prognostic significance carotid IMT >1.0

46. Arterial anatomy extracranial Courtesy of M Bin Zulfiqar

47. Arterial Carotid Artery Intimal Medial Thickness Courtesy of M Bin Zulfiqar

48. Pulse Wave Velocity

49. Pulse Wave Velocity Speed of the pulse wave down the full aorta Cuffs over the carotid and femoral arteries PWV = Distance/Time Distance = Carotid - femoral distance Time = Lag between carotid & femoral waveforms

50. Arterial stiffness • Pulse Wave Velocity (PWV) is a measure of arterial (aortic) stiffness • Stiffness is the inverse of compliance (∆Diameter/∆ Pressure) • Higher PWV = stiffer arteries • Large arteries buffer pressure changes from ventricular contraction • Windkessel effect