Human Anatomy and Physiology...E. MORAN - 2018. 86. Genes encode enzymes active in the metabolism of...
Transcript of Human Anatomy and Physiology...E. MORAN - 2018. 86. Genes encode enzymes active in the metabolism of...
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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
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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
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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
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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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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
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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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
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
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
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Left cervical lymphadenopathy
(Enlarged lymph nodes) – Chronic
lymphatic leukemia (CLL)
What Causes Cancer?
Some viruses or bacteria
HeredityDiet
Hormones
RadiationSome chemicals
N.C.I. 55
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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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
Cancer Viruses
Human Papylloma Virus (HPV)
Noninfected women
HPV Infection Increases Risk for Cervical Cancer
CervicalCancerRisk
Low
High
Womeninfected
with HPVN.C.I. 80
E. MORAN - 2018 86
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
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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)
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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)
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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
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
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Cancer Mortality Rate Down 26%
134,000 lives saved/yearAffordable Care Act → earlier diagnosis
LA TIMES JULY 13, 2018 94