WHY s IN BIOLOGY AND HEALTHCARE

Transcription

1 Session #2 1

2 WHY s IN BIOLOGY AND HEALTHCARE 1. Why do we get infections? 2. Why do we inherit characteristics / traits? 3. Why do we become obese? 4. Why so many people have hypertension? 5. Why do we get cancer? 6. Why do we age? 7. Why is physical exercise helpful to us? 8. Why are we different? E. MORAN

3 WHY SO MANY PEOPLE HAVE HYPERTENSION? 16-37% OF THE GLOBAL POPULATION 3

4 ARTERIAL HYPERTENSION A chronic disease characterized by elevation of the blood pressure >130/80 mmhg. Essential HTN - Cause unknown % of cases Secondary HTN - Kidney pathology - Endocrine dysfunctions E. MORAN

5 Causes of Hypertension Complex interaction of genes and environmental factors. Many common genetic variants with small effects on BP and some genetic variants with large effects on BP. Genome-wide association studies (GWAS) - 35 genetic loci related to HBP. Genes related to vascular smooth muscle and renal function. E. MORAN

6 Causes of Hypertension (Cont d) Aging (over 50-60) High salt intake Obesity Lack of exercise Vitamin D deficiency Caffeine consumption (?) Insulin resistance (?) E. MORAN

7 Symptoms Rarely present, Headaches, Vertigo, Tinnitus, Lightheadedness. Hypertensive crisis = A medical emergency Confusion, Drowsiness, Chest pain, Shortness of breath. E. MORAN

8 Diagnosis Sphygmomanometer (blood pressure cuff) or digital devices. Three measurements at monthly intervals. Sitting, feet flat on the floor. Same bare arm. Systolic (maximum) >130 mmhg at rest Diastolic (minimum) > 80 mmhg at rest Most accurate diagnosis is the ambulatory BP monitoring over hours. E. MORAN

9 Classification of HBP in Adults Category Systolic, mmhg Diastolic, mmhg Hypotension < 90 < 60 Normal Stage 1 HBP Stage 2 HBP > 140 > 90 Hypertensive crisis > 180 > 120 E. MORAN

10 Genetics: Familiar incidence Autonomic Nervous System: Arterial baroreceptors Renin - Angiotensin - Renin System: Renin (from kidneys) breaks down Angiotensinogen (from liver) into Angiotensin I; Angiotensin I is cleaved by Angiotensin-Converting enzyme (ACE) (from pulmonary circulation) into Angiotensin II which constricts blood vessels peripheral resistance. Angiotensin II also causes the adrenals to release aldosterone which stimulates the kidney to increase the reabsorption of water and salt raises blood volume and BP. Endothelial Dysfunction ESSENTIAL HYPERTENSION PATHOPHYSIOLOGY E. MORAN

11 Complications of HBP 11

12 Complications of Hypertension Brain: Cerebrovascular accident (stroke) Hypertensive encephalopathy (confusion, headaches) Heart: Heart failure, Myocardial infarction Kidneys: Hypertensive nephropathy, chronic kidney failure Eyes: Hypertensive retinopathy Blood: Elevated sugar levels E. MORAN

13 Cross-section of an artery and vein 13

14 ATHEROSCLEROSIS 14

15 Atheroma Plaque 15

16 Hypertensive Retinopathy 16

17 Atheroma and Thrombus 17

18 ACUTE MYOCARDIAL INFARCTION 18

19 VASCULAR ISCHEMIC EVENTS (I) Acute - d/t closure of blood supply by a blood clot (thrombus) Chronic - d/t narrowing of arteries by: Atherosclerosis = hardening of arteries E. MORAN

20 VASCULAR ISCHEMIC EVENTS (II) Brain - Transient ischemic attack (TIA) or - Cerebral vascular accident (CVA, Stroke) Heart Angina, or Heart attack (Myocardial infarct or MI) Limbs Claudication, Peripheral vascular insufficiency (PVI) Lung Pulmonary infarct Kidney, Spleen - Infarcts E. MORAN

21 Transient Ischemic Attack (TIA) Symptoms: Weakness, numbness or paralysis in the face, arm or leg, typically on one side of your body, Slurred or garbled speech or difficulty understanding others, Blindness in one or both eyes or double vision, Dizziness or loss of balance or coordination, Sudden, severe headache with no known cause. E. MORAN

22 STROKE or CVA Warning signs: Confusion Difficulty speaking and understanding Numbness or weakness on one side of the body Impaired vision Sudden severe headache E. MORAN

23 Stroke - Management FAST Diagnosis: F = Face drooping A = Arm weakness S = Speech impairment T = Time is of the essence CT scan or MRI or MRA Ischemic stroke Tissue plasminogen activator E. MORAN

24 Hypertension in Pregnancy Incidence: 8-10% of pregnancies. 1. Gestational hypertension 2. Pre-eclampsia: 5% of pregnancies and 16% of all maternal deaths. Protein in urine, headaches, visual disturbance, vomiting, water retention. 3. Eclampsia: Medical emergency Vision loss, brain edema, seizures, kidney failure, lung edema, DIC. High mortality rate. Remember Lady Sybil of Downton Abbey E. MORAN

25 Primary Prevention of Hypertension Normal body weight for adults (BMI 20-25kg/m 2 ) Aerobic exercise (brisk walking 30 min. X5/week) Low sodium diet (<6 gm NaCl) Limit alcohol intake to 3 drinks/day for men, 2 drinks/day for women Diet rich in fruits and vegetables (5 exchanges/day) E. MORAN

26 Lifestyle modifications: 1. Weight loss 2. Physical exercise 3. Low salt diet (<3gm/day) Treatment Medications added if BP not controlled: 1. Diuretics 2. Angiotensin converting enzyme (ACE) inhibitors 3. Angiotensin receptor blockers 4. Calcium channel blockers E. MORAN

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28 WHY DO WE GET CANCER? 28

29 Cancer Statistics in USA 2017* and Est. 2018** All sites Lung Breast Prostate Colon (W) New cases 1,689, , , ,000 96,000 1,735, , , ,000 97,000 Deaths 601, ,000 41,000 27,000 50, , ,000 41,000 29,000 51, * Published 2017 ** Published 2018 E. MORAN

30 Cancer = Malignant Tumor A tissue growth: Not necessary for body s development or repair Invading healthy tissues Spreading to other sites of the body (metastasizing) Lethal because of its invasion, metabolism, and complications E. MORAN

31 Malignant vs. Benign Benign tumors do not invade surrounding healthy tissues Benign tumors do not spread out Benign tumors may cause complications due to obstruction of natural conduits (airways, intestine) Terms: Adenoma, lipoma E. MORAN

32 Terms to Know Carcinoma = Cancer of epithelial cells (lung, breast, prostate, stomach, colon) Sarcoma = Cancer of muscle, bone, cartilage Lymphoma = Cancer of lymphatic organs Leukemia = Cancer of blood cells Glioma = Cancer of brain cells E. MORAN

33 CARCINOGENESIS 33

34 Apoptosis = Programmed Cell Death Definition: A highly regulated and controlled cell death. Defective apoptotic processes have been implicated in a wide variety of diseases. An insufficient amount results in uncontrolled cell proliferation, such as cancer Between 50 and 70 billion cells die each day due to apoptosis in the average human adult E. MORAN

35 APOPTOSIS 35

36 Phases of Apoptosis 36

37 Oncogenes Normal cell Normal genes regulate cell growth Cancer cell Oncogenes accelerate cell growth and division Mutated/damaged oncogene N.C.I. 37

38 p53 Tumor Suppressor Protein Triggers Cell Suicide p53 protein Normal cell Excessive DNA damage Cell suicide (Apoptosis) N.C.I. 38

39 E. MORAN

40 Chances of Genomic Instability Human Body Cells ~ Lifetime Cell Divisions ~10 16 Chances of Mutation ~ E. MORAN

41 (Polycyclic Aromatic Hydrocarbons) E. MORAN

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43 N.C.I. 43

44 N.C.I. 44

45 N.C.I. 45

46 N.C.I. 46

47 N.C.I. 47

48 Malignant versus Benign Tumors Benign (not cancer) Tumor cells grow only locally and do not spread by invasion or metastasis Malignant (cancer) cells invade neighboring tissues, enter blood vessels, and metastasize (spread) to different sites Time N.C.I. 48

49 Development of a Malignant Tumor E. MORAN

50 Cancer Invasion E. MORAN

51 Tumor Embolus E. MORAN

52 Hodgkin s disease of the mediastinum with metastases to the right cervical area E. MORAN

53 Left cervical lymphadenopathy (Enlarged lymph nodes) Chronic lymphatic leukemia (CLL) E. MORAN

54 INTERMISSION 54

55 What Causes Cancer? Some viruses or bacteria Some chemicals Radiation Heredity Diet Hormones N.C.I. 55

56 Heredity and Cancer All Breast Cancer Patients Inherited factor(s) Other factor(s) N. C. I. 56

57 Cancer Risk and Aging 400 Cancer Risk and Aging Colon Number of Cancer Cases (per 100,000 people) Breast Age of Person (in years) N.C.I. 57

58 Population - Based Studies U.K.: Lung cancer Regions of Highest Incidence JAPAN: Stomach cancer CANADA: Leukemia CHINA: Liver cancer AUSTRALIA: Skin cancer U.S.: Colon cancer BRAZIL: Cervical cancer N.I.H. 58

59 Heredity? Behaviors? Other Factors? 100 Colon Cancer (Number of new cases per 100,000 people) 100 Stomach Cancer (Number of new cases per 100,000 people) Japan Japanese families in U.S. U.S. born. 7 0 Japan Japanese families in U.S. U.S. born. born N.C.I. 59

60 E. MORAN

61 E. MORAN

62 ENVIRONMENT AND CANCER 62

63 Known Exogenous Carcinogens By air: Exposure to combustion of fossil fuels Cigarettes smoking (Active and passive) Exposure to asbestos (Certain types of asbestos) Nuclear power High strength radiation (Melanoma) Low strength radiation (Solar) Bacteria (Helicobacter) & Viruses (HPV) By ingestion: Water pollution (Chemical fertilizers, pesticides, THM) Industrial pollution Alcohol E. MORAN

64 AIR POLLUTION and CANCER Combustion of fossil fuels Smoking Asbestos Radon gas E. MORAN

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66 E. MORAN

67 E. MORAN 2018

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78 Low-Strength Radiation High Dallas Skin Cancer Incidence Detroit Pittsburgh Low Least Annual Sunshine (UV radiation) Most N.C.I. 78

79 High-Strength Radiation High Leukemia Incidence Low Least X-ray Dose (atomic radiation) Most N.C.I. 79

80 Cancer Viruses Human Papylloma Virus (HPV) High HPV Infection Increases Risk for Cervical Cancer Cervical Cancer Risk Low Noninfected women Women infected with HPV N.C.I. 80

81 Bacteria and Stomach Cancer Patient s tissue sample H. pylori N.I.H. 81

82 E. MORAN

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84 E. MORAN

85 E. MORAN

86 Alcohol, Cancer, and Genes Genes encode enzymes active in the metabolism of alcohol. Alcohol dehydrogenase (ADH) is a variant of such gene. Many Chinese, Koreans, and Japanese inherit a superactive type of ADH speeds up the conversion of alcohol to toxic acetaldehyde Increased risk of pancreatic ca. Aldehyde dehydrogenase 2 (ALDH2) metabolizes toxic acetaldehyde to non-toxic substances. Some people of East Asian origin have a defective form of ALDH2 acetaldehyde builds up carcinogen. E. MORAN

87 Alcohol and Cancer (1) Alcohol = ethanol = ethyl alcohol is produced by the fermentation of sugars and starches by yeast. Beers 3-7% alcohol Wines 9-15% alcohol Liquor (distilled spirits: whiskey, gin, vodka, from fermented grains, fruits, or vegetables) 35-40% alcohol (70-80 proof) U.S. drink = 12 oz. beer, 5 oz. wine, 1.5 oz. 80-proof liquor ( a shot ) = 14 gm or 0.6 oz. of pure alcohol E. MORAN

88 Alcohol and Cancer (2) Natl. Toxicology Program of the U.S. Dept. of HHS: 3.5% of all cancer deaths are alcohol-related Parameters: Daily use + Quantity + Duration Alcohol-related cancers: Head and Neck cancer 3.5 drinks/day x 2-3 times greater risk. Usually smokers. Esophageal cancer Usually smokers Liver cancer Breast cancer 3 drinks/day x 1.5 times greater risk. Every 10 gm (= less than one drink) 12% increased risk. E. MORAN

89 WHY does alcohol increase the risk of cancer Ethanol metabolized (broken down) to acetaldehyde toxic chemical, probably carcinogenic. Damages DNA and proteins. Generates Reactive Oxygen Species (ROS) damages DNA, proteins, lipids by oxidation. Impairs the ability to absorb nutrients (vitamin A, B, folate, C, D, E and carotenoids). Increases blood level of estrogen. Risk of breast cancer. Alcohol + tobacco greater risk of cancer E. MORAN

90 E. MORAN

91 Diet: Limit Fats and Calories Correlation Between Meat Consumption and Colon Cancer Rates in Different Countries 40 Number of cancer cases (per 100,000 people) Grams (per person per day) N. C. I. 91

92 CANCER DEATH RATES OF OBESE COMPARED TO THAT OF INDIVIDUALS WITH NORMAL BODY WEIGHT (BMI < 25) 70% 60% 50% Men Women 52% 62% 40% 30% 20% 10% 0% or more 92

93 OBESITY AND CANCER NEW FINDINGS ~30% of adults are obese (BMI > 30) ~35% of adults are overweight (BMI 25-30) Women: Uterine cancer x 6 Men: Kidney cancer x 5 Liver cancer 6-fold Colorectal cancer ~1.75-fold E. MORAN

94 Cancer Mortality Rate Down 26% 134,000 lives saved/year Affordable Care Act earlier diagnosis LA TIMES JULY 13,

95 END OF SESSION #2 95