Session #2

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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?

WHY’s IN BIOLOGY AND HEALTHCARE

E. MORAN - 2018

WHY SO MANY PEOPLE HAVE

HYPERTENSION?

16-37% OF THE GLOBAL POPULATION

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E. MORAN - 2018 4

A chronic disease characterized by elevation of the

blood pressure >130/80 mmHg.

Essential HTN - Cause unknown - 90-95% of cases

Secondary HTN - Kidney pathology

- Endocrine dysfunctions

ARTERIAL HYPERTENSION

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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.

Causes of Hypertension

E. MORAN - 2018

E. MORAN - 2018 6

Aging (over 50-60)

High salt intake

Obesity

Lack of exercise

Vitamin D deficiency

Caffeine consumption (?)

Insulin resistance (?)

Causes of Hypertension (Cont’d)

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• Rarely present,

• Headaches,

• Vertigo,

• Tinnitus,

• Lightheadedness.

Hypertensive crisis = A medical emergency

• Confusion,

• Drowsiness,

• Chest pain,

• Shortness of breath.

Symptoms

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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 12-24 hours.

Diagnosis

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Category Systolic, mmHg Diastolic, mmHg

Hypotension < 90 < 60

Normal 90-129 60-79

Stage 1 HBP 130-139 80-89

Stage 2 HBP > 140 > 90

Hypertensive crisis > 180 > 120

Classification of HBP in Adults

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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 HYPERTENSIONPATHOPHYSIOLOGY

Complications of HBP

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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

Complications of Hypertension

Cross-section of an artery and vein

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ATHEROSCLEROSIS

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Atheroma Plaque

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Hypertensive Retinopathy

Atheroma and Thrombus

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ACUTE MYOCARDIAL INFARCTION

Acute - d/t closure of blood supply by a blood clot

(thrombus)

Chronic - d/t narrowing of arteries by:

Atherosclerosis = hardening of arteries

VASCULAR ISCHEMIC EVENTS (I)

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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

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Transient Ischemic Attack (TIA)

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• 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.

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Warning signs:

• Confusion

• Difficulty speaking and understanding

• Numbness or weakness on one side of the body

• Impaired vision

• Sudden severe headache

STROKE or CVA

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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

Stroke - Management

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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

Hypertension in Pregnancy

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• Normal body weight for adults (BMI 20-25kg/m2)

• 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)

Primary Prevention of Hypertension

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Lifestyle modifications:

1. Weight loss

2. Physical exercise

3. Low salt diet (<3gm/day)

Medications added if BP not controlled:

1. Diuretics

2. Angiotensin converting enzyme (ACE) inhibitors

3. Angiotensin receptor blockers

4. Calcium channel blockers

Treatment

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WHY DO WE GET CANCER?

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Cancer Statistics in USA – 2017* and Est. 2018**

All sites Lung Breast Prostate Colon

(W)

New cases 1,689,000 222,000 255,000 161,000 96,000

1,735,000 234, 000 268,000 165,000 97,000

Deaths 601,000 156,000 41,000 27,000 50,000

610,000 154,000 41,000 29,000 51,000

--------

* Published 2017

** Published 2018

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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

Cancer = Malignant Tumor

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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

Malignant vs. Benign

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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

Terms to Know

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CARCINOGENESIS

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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

Apoptosis = Programmed Cell Death

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APOPTOSIS

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Phases of Apoptosis

Oncogenes

Mutated/damaged oncogene

Oncogenesacceleratecell growthand division

Cancer cell

Normal cell Normalgenesregulate

cell growth

N.C.I. 37

p53 Tumor Suppressor ProteinTriggers Cell Suicide

Normal cell Cell suicide(Apoptosis)

p53 protein

Excessive DNA damage

N.C.I. 38

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Human Body Cells ~ 1014

Lifetime Cell Divisions ~1016

Chances of Mutation ~ 10224

Chances of Genomic Instability

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(Polycyclic Aromatic

Hydrocarbons)

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N.C.I. 43

N.C.I. 44

N.C.I. 45

N.C.I. 46

N.C.I. 47

Malignant versus Benign Tumors

Malignant (cancer) cells invade neighboring tissues, enter blood vessels, and metastasize (spread) to different sites

Time

Benign (not cancer) Tumor cells grow only locally and do not spread by invasion or metastasis

N.C.I. 48

Development of a Malignant Tumor

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Cancer Invasion

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Tumor Embolus

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Hodgkin’s disease of the mediastinum with metastases to the right cervical area

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Left cervical lymphadenopathy

(Enlarged lymph nodes) – Chronic

lymphatic leukemia (CLL)

INTERMISSION

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What Causes Cancer?

Some viruses or bacteria

HeredityDiet

Hormones

RadiationSome chemicals

N.C.I. 55

Heredity and Cancer

Inherited factor(s)

All Breast Cancer Patients

Other factor(s)

N. C. I. 56

Cancer Risk and Aging

400

300

200

100

Cancer Risk and Aging

Number of Cancer Cases(per 100,000 people)

Age of Person (in years)

Colon

Breast

0 20 40 60 80

N.C.I. 57

Population - Based Studies

CANADA:Leukemia

Regions of Highest Incidence

BRAZIL:Cervicalcancer

U.S.:Coloncancer

AUSTRALIA:Skincancer

CHINA:Livercancer

U.K.:Lungcancer

JAPAN:Stomachcancer

N.I.H. 58

Heredity? Behaviors? Other Factors?

100

50

50

Stomach Cancer(Number of new cases per 100,000 people)

U.S.born.born

Japan Japanese familiesin U.S.

100

70

7

0

Colon Cancer(Number of new cases per 100,000 people)

U.S.born.

Japan Japanese familiesin U.S.

N.C.I. 59

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ENVIRONMENT AND CANCER

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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

Known Exogenous Carcinogens

AIR POLLUTION and CANCER

• Combustion of fossil fuels

• Smoking

• Asbestos

• Radon gas

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Low-Strength Radiation

Annual Sunshine(UV radiation)

SkinCancerIncidence

Most

Dallas

Pittsburgh

High

Detroit

LowLeast

N.C.I. 78

High-Strength Radiation

Most

High

LowLeast

LeukemiaIncidence

X-ray Dose(atomic radiation)

N.C.I. 79

Cancer Viruses

Human Papylloma Virus (HPV)

Noninfected women

HPV Infection Increases Risk for Cervical Cancer

CervicalCancerRisk

Low

High

Womeninfected

with HPVN.C.I. 80

Bacteria and Stomach Cancer

H. pyloriPatient’s tissue sample

N.I.H. 81

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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.

Alcohol, Cancer, and Genes

E. MORAN - 2018 87

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

Alcohol and Cancer (1)

E. MORAN - 2018 88

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.

Alcohol and Cancer (2)

E. MORAN - 2018 89

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

WHY does alcohol increase the risk of cancer

E. MORAN - 2018 90

Diet: Limit Fats and Calories

0

Number of cancer cases (per 100,000 people)

Grams (per person per day)

Correlation Between Meat Consumption and Colon Cancer Rates in Different Countries

40

30

20

10

30020010080

N. C. I. 91

CANCER DEATH RATES OF OBESE COMPARED TO THAT OF INDIVIDUALS WITH NORMAL BODY WEIGHT (BMI < 25)

0%

10%

20%

30%

40%

50%

60%

70%

30.0-34.9 35.0-39.9 40 or more

Men

Women52%

62%

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OBESITY AND CANCERNEW FINDINGS

• ~30% of adults are obese (BMI > 30)

• ~35% of adults are overweight (BMI 25 - 30)

• Women: Uterine cancer x 6

Kidney cancer x 5

• Men: Liver cancer 6-fold

Colorectal cancer ~1.75-fold

E. MORAN - 2017 93

Cancer Mortality Rate Down 26%

134,000 lives saved/yearAffordable Care Act → earlier diagnosis

LA TIMES JULY 13, 2018 94

END OF SESSION #2

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