CHAPTER 13 – DIABETES

I. DIABETES MELLITUS
a. Diabetes – flow of much urine
b. Mellitus – sweet urine
c. Prevalence: > 20 million diabetics in the US
d. Undiagnosed: 1/3
e. TRENDS:
i. 4.9% in 1990
ii. 9.4% in 2015
iii. Predicted to more than double by 2050
f. REASONS FOR EXPONENTIAL RISE:
i. Poor diet, decrease in exercise, increase in prevalence of obesity
II. TYPES OF DIABETES
a. Type 1 diabetes
b. Type 2 diabetes
c. Gestational diabetes
III. TYPE 1 DIABETES
a. Begins at 8-12 years
b. Beta-cells are destroyed  unable to produce insulin
i. Autoimmune disease (body attacks itself)
ii. Infection
c. Increased blood glucose
d. SYMPTOMS:
i. Frequent urination (polyuria)  To get rid of excess glucose
ii. Unusual thirst (polydipsia)  IOT replenish fluids that are being urinated
iii. Extreme hunger (polyphagia)  cells are not getting the energy they need from glucose because
the body has an issue with insulin
iv. Unusual weight loss
v. Extreme fatigue
vi. Irritability
vii. Ketosis
e. Whites are more likely to develop type 1 diabetes
f. Decreased insulin levels and corresponding increase in glucagon levels
i. Less glucose uptake by the cell
ii. Increase breakdown of glycogen
iii. Increase gluconeogenesis in liver
1. ^All of the above  increasing glucose levels in the blood  increasing glucose levels in the
urine which draws electrolytes (Na and K) and water  causes polyuria, dehydration,
electrolyte imbalance, and compensatory thirst (polydipsia)
g. Ketosis
i. Decreased insulin  free fatty acids are mobilized from adipocytes to liver  fatty acids
converted to ketone bodies (acetoacetate and beta-hydroxybutyrate in liver  increases ketone
bodies in blood  ketones excreted in urine  ketones draw Na and K ion water  electrolyte
imbalance, dehydration, coma, and death
h. Treatment for type 1 diabetes
i. Insulin therapy
ii. CHO counting
IV. GESTATIONAL DIABETES
a. Transient condition
b. Occurs in 2-5% of pregnancies
c. RISK FACTORS:
i. Age, family history, obesity, glycosuria, stillbirth or large baby during previous pregnancy
d. POSSIBLE CONSEQUENCES:
 i. Large fetus  delivery problems
ii. HTN
iii. 50% with gestational diabetes  type 2 diabetes by 5 years postpartum
iv. Offspring develops type 2 diabetes
e. PREVENTION/TREATMENT: ?
V. TYPE 2 DIABETES
a. Accounts for 90-95% of all cases
b. Usually begins after age 40
c. Age of onset is changing
i. Now being seen in teenagers
d. Minorities vs. whites
e. DIAGNOSIS OF TYPE 2 DIABETES
i. Fasting blood glucose
1. Diabetic (if diabetic, repeat test to confirm results)
2. Pre-diabetic
3. Normal
ii. Oral glucose tolerance test
1. Drink liquid containing 75g glucose after overnight fast
2. Blood glucose measured for 2 hours after glucose consumption
a. Diabetic:  200 mg/dL
b. Pre-diabetic: 140-199 mg/dL
c. Normal: < 140 mg/dL
iii. Glycated (or glycosylated) HbA1c
1. Type 2 diabetes:  6.5%
2. Pre-diabetes:  5.6% but less than 6.5%
3. Normal: < 5.6%
f. RISK FACTORS**
i. Abdominal obesity (major cause of T2D)
1. 80% of type 2 diabetics are obese when diagnosed
ii. Abdominal obesity is linked to insulin resistance
iii. Insulin resistance (IR) is characterized by:
1. Impaired insulin mediated glucose uptake into cells
2. Impaired suppression of hepatic glucose synthesis
3. (both affected by free fatty acids)
a. Fatty acids go to the cells and liver; makes the liver create more insulin
iv. How do the following lead to type 2 diabetes?
1. Insulin resistance
2. Inadequate compensatory beta cell function
v. Role of central obesity in IR
1. Role of free fatty acids in IR  accumulation in muscle and liver
2. Role of cytokines in IR  block signal
3. Role of adipokines in IR  increase fat oxidation
vi. Why do only some obese develop diabetes?
1. You have to be insulin resistant and have inadequate compensatory beta cell function – if an
obese person doesn’t have both, they won’t become diabetic
vii. Insulin resistant but the beta cells make more insulin  end up with normal glycemia
viii. South Asians easily become diabetic  genetically don’t have enough beta cell reserve
ix. CYTOKINES  macrophage engulfs the fat cells which releases inflammatory markers, which then
blocks the signal
x. ADIPOKINES: adiponectin  INCREASE FAT OXIDATION – a good thing, you burn fat which
prevents insulin resistance
1. Fat people don’t produce this hormone
xi. How can you attenuate genetic predisposition?
 1. Exercise
2. Weight maintenance
xii. Advancing age  insulin resistance
xiii. Inactivity  insulin resistance
1. Physical activity  increase insulin sensitivity
xiv. Smoking
xv. Low fiber diet
VI. DIABETES COMPLICATIONS
a. Macrovascular damage
i. Heart disease
ii. Stroke
iii. Peripheral vascular disease
b. Microvascular damage
i. Kidney disease
ii. Blindness
iii. Nerve damage
c. Glucose levels and micro/macro-vascular damage
VII. MICROVASCULAR COMPLICATIONS – damage to small blood vessels
a. BLINDNESS
i. High blood glucose binds with proteins in the tiny blood vessels in the retina  glycated proteins
damage blood vessels in the retina  retinopathy, which could eventually lead to blindness
ii. Retinopathy is very common
iii. Some develop macular edema  blood vessels leak fluid and lipids into the macula, causing blurry
vision
iv. Laser treatment can stop the bleeding
v. May not have any symptoms during early stages
vi. Leading cause of new causes of blindness
b. KIDNEY PROBLEMS
i. > 35% of diabetics will develop kidney disease
ii. High blood glucose bind with proteins in small blood vessels in the glomeruli  glycated proteins
damage wall of small blood vessels  become thick and bleed, leak protein, slow blood flow 
diabetic neuropathy
iii. Diabetic neuropathy
1. Albuminuria
2. Hypertension
3. Progressive renal insufficiency
iv. Leading cause of kidney failure
v. ACE inhibitors  decreases BP  prevents progression of kidney disease
c. NERVE DAMAGE
i. Glycated proteins  injury to small blood vessels to the nerves  peripheral neuropathy
ii. Prevalence = 60-70%
iii. Numbness/tingling sensation in feet and hands; poor circulation
iv. Leads to:
1. Injury, infection, amputations
2. Erectile dysfunction
3. Cognitive decline
4. Slows digestion  causes intermittent diarrhea and constipation
5. Carpel tunnel syndrome
v. Intensive therapy delays onset and slows progression of complications
d. PREVENTING FOOT ULSERS
i. Prevalence: 4-10%
ii. Proper foot care:
 1. Intensive podiatric care, periodic examinations, debridement of calluses, prescription
footwear
VIII. MACROVASCULAR COMPLICATIONS – damage to large blood vessels
a. CVD
i. Major cause of death in diabetics
ii. A diabetic is 2-4x more likely to die from heart disease than non-diabetics
iii. Diabetes for 25y  10x more likely to die from diabetes than a non-diabetic
iv. RISK FACTORS***
1. Too much glucose
a. Glycated proteins
i. Damages blood vessels
ii. Blood vessels are more rigid  atherosclerosis
2. Insulin resistance
3. High levels of TGs and VLDL
a. Excess glucose converted to fat
4. High levels of small dense LDL
DYSLIPIDEMIA
5. Low levels of HDL
6. High blood pressure (HTN)
7. Linked to metabolic syndrome
IX. PREVENTION AND TREATMENT
a. AMERICAN DIABETIC ASSOCIATION 2015 – LIFESTYLE RECOMMENDATIONS FOR DIABETICS
i. Weight loss is recommended for overweight or obese  better control of blood glucose levels
1. #1 RECOMMENDATION FOR OBESE PEOPLE
ii. Regular exercise  improves insulin sensitivity
iii. Portion control for weight loss and maintenance
iv. Choose nutrient-dense, high-fiber foods instead of processed foods with added sodium, fat, and
sugars (want digestion and absorption to slow down)
1. Fruit, vegetables, whole grains, legumes, and low-fat milk
v. Avoid sugar-sweetened beverages
vi. No need to subtract dietary fiber and sugar alcohols from total CHO counting
b. LIFESTYLE RECOMMENDATIONS (ADA, 2015)
i. Substitute foods higher in unsaturated fat (liquid oils) instead of foods higher in trans and
saturated fats
ii. Select leaner protein sources and meat alternatives
iii. Supplements are not recommended to manage diabetes due to lack of evidence
iv. Moderate alcohol consumption has minimal effects on blood glucose and should be consumed with
food
v. Limit sodium intake to 2,300 mg/day
c. INTERVENTION: STUDY TO PREVENT DIABETES
i. Avg. fasting glucose: 106.5 mg/dL
ii. Randomized for 3 years to:
1. Placebo
2. Metformin (850 mg twice daily)
3. Lifestyle modification
a. Lose weight ( 7% of body weight)
b. Perform  150 min/week of aerobic physical activity
iii. Results:
1. Lifestyle intervention reduced the incidence of diabetes by 58% and metformin by 31% vs.
placebo
2. Lifestyle intervention was significantly more effective than metformin
d. LIFESTYLE STUDY TO TREAT DIABETES
i. Gregg et al., JAMA 2012
1. Overweight/obese individuals with T2D randomized for 4 years to:
 a. Intensive lifestyle intervention: calorie reduction + exercise
b. Diabetes support and education
2. Results:
a. Intensive lifestyle intervention: 7.3% partial or complete remission
b. Diabetes support and education: 2.0% partial or complete remission
c. No difference in cardiovascular events between groups
ii. Bypass surgery
1. Higher rates of diabetes remission and lower risk for CVD events
X. PHARMACOTHERAPY
a. SULFONYLUREAS
i. Stimulates insulin secretion
ii. Glipizide, Glyburide, Glimepiride, Gliclazide
iii. May cause weight gain and hypoglycemia
b. MEGLITINIDES
i. Stimulates insulin secretion
ii. Repaglinide, Nateglinide
iii. May cause weight gain and hypoglycemia
c. GLP-1 RECEPTOR AGONISTS
i. Activates GLP-1 receptors (results in insulin secretion)
ii. Slows gastric emptying
iii. Increases satiety and causes weight loss
iv. Exenatide, Liraglutide
v. May cause nausea and vomiting and occasionally acute pancreatitis
d. DPP-4 INHIBITORS
i. Slows down breakdown of GLP-1 and increases glucose dependent insulin secretion
ii. Sitagliptin, saxagliptin, vildagliptin, linagliptin, alogliptin

iii. May cause pancreatitis

e. BIGUANIDES
i. Decreases hepatic glucose production
ii. Metformin (glucophage)
iii. May cause flatulence, and diarrhea, lactic acid deficiency (rare), vitamin B deficiency (rare)
iv. May cause small weight loss
f. THIAZOLIDINEDIONES
i. Act as peripheral level to increase insulin sensitivity
ii. Pioglitazone and Rosiglitazone
iii. May cause weight gain, edema, bone fractures, etc.
iv. Rosiglitazone has been linked to heart attacks
g. ALPHA-GLUCOSIDASE INHIBITORS
i. Delay carbohydrate digestion and absorption
ii. Acarbose, Miglitol, Voglibose
iii. May cause flatulence and diarrhea
h. INSULIN THERAPY
i. Increase glucose disposal and decreases hepatic glucose production
ii. Injections, nasal, or pump
iii. Side effects:
1. Weight gain
2. Hypoglycemia  can cause arrhythmias and mortality
i. Improve lipid profile (HDL, LDL, TG)
j. Low dose aspirin
k. NATIONAL DIABETES EDUCATION PROGRAM – KNOW YOUR ABCs
i. Hba1c: 2x per year
ii. Blood pressure: at every clinic visit
 iii. Cholesterol (LDLC): at least once a year

CHAPTER 14 – LUNG DISEASES

I. CHRONIC LUNG DISEASES
a. Chronic lower respiratory disease (COPD) = 4th leading cause of death
i. Irreversible; no treatment; not much you can do
ii. 6.3% of US adults with COPD – chronic bronchitis and emphysema
II. COPD
a. Chronic bronchitis and emphysema
b. PRIMARY CONSEQUENCE: dyspnea (breathlessness); unable to take in oxygen
c. OTHER SYMPTOMS:
i. Excess phlegm (mucus)
ii. Cough
iii. Wheezing
iv. Hemophysis (coughing blood) – in later stages
d. DISABILITY: ranges from inability to climb stairs to difficulty sleeping
e. DIAGNOSIS:
i. Spirometry  forced expiratory volume in the first 1 second (FEV1)
1. Healthy lungs should be able to get their entire volume out in one second after maximal
inspiration
ii. Chest x-rays
iii. CT scan
f. PATHOPHYSIOLOGY
i. RISK FACTORS:
1. Smoking, air pollution, chemical fumes, dust, exposure to secondhand smoke
ii. Changes in bronchioles and lung function (parenchyma) leading to emphysema and airflow
obstruction
iii. DUE TO:
1. Increase in mucous gland size
2. Increase in mucous gland numbers
3. Inflammation
4. Fibrosis
iv. EMPHYSEMA
1. Destruction of elastin (protein) in alveoli walls  destruction of alveoli (tiny elastic air
sacs)
2. Elastin is needed to maintain strength of the alveolar walls
v. Impairment in lung function is largely irreversible
vi. After 7.5 years, most patients are no longer capable of productive work
vii. “Smoker’s Emphysema”
1. Due to imbalance in the lungs between elastase and alpha-1-antitrypsin (AAT) – lots of
elastase, not enough AAT
a. Elastase  breaks down elastin
b. AAT  inhibits action of elastase
2. Tobacco smoke:
a. Increases release of elastase from lungs
b. Stimulates more elastase-producing cells to migrate to the lungs
c. The free radicals inactivate most AAT
viii. Other factors can also cause emphysema
1. Familial emphysema (have a hereditary deficiency of AAT)
ix. Onset of COPD in adults begins before age 50
x. Moderate decline in lung function
1. Dyspnea or cough with sputum
2. Winded climbing a flight of stairs
 xi. Significance of symptoms often not recognized
xii. After age 50: decline in lung function accelerates
xiii. Advanced stage: inadequate oxygen delivery
1. Blue lips (from low oxygen saturation)
xiv. COPD is often accompanied by heart failure
g. EPIDEMIOLOGY
i. Mortality from COPD is higher in men than women
1. Smoking rates are higher in men
2. Earlier initiation of smoking in men
h. PREVENTION AND CONTROL
i. FEV1 naturally decreases with age
1. In smokers, this decrease is accelerated
ii. SMOKING CESSATION:
1. Will bring the rate of decline of FEV1 to the rate seen in non-smokers
2. Absolute level of FEV1 still lower in ex-smokers than in non-smokers of similar age
iii. Low FEV1 is a risk factor for mortality
iv. TREATMENT OF COPD
1. Inhaled bronchodilator drugs
2. Inhaled glucocorticoid steroids + bronchodilators
3. Oxygen therapy as disease progresses
a. Oxygen through nasal prongs or a mask
4. Bullectomy
a. When the air sacs (alveoli) are destroyed, larger spaces called bullae form
5. Lung Volume Reduction Surgery
a. Damaged tissue from the lungs is removed
6. Lung Transplant
III. ASTHMA
a. EPIDEMIOLOGY
i. RISK FACTORS:
1. Ethnicity (higher in blacks than whites)
2. Higher in those under 18 y/o
3. Gender (more in females)
4. Family history
5. Living in inner cities (pollution; air quality)
ii. 1980 to present:
1. Prevalence has nearly doubled
2. Highest increase among 0-4 y/o
iii. Explanations for rising prevalence:
1. Increased awareness
2. More accurate diagnosis
3. Rising incidence
iv. MORTALITY RATES due to asthma are higher in:
1. Females compared to males
2. Blacks and Hispanics compared to Whites
3. Lack of access to medical care
4. Inadequate medical management
5. History of previous life-threatening asthma
6. Alcoholics
7. Depression
b. PATHOPHYSIOLOGY
i. Asthma = airway inflammation
ii. CAUSES: interplay between environmental exposures and genetic factors
 iii. CHARACTERIZED BY: recurrent episodes of breathlessness, wheezing, coughing, and chest
tightness
iv. LEFT UNTREATED  irreversible changes in lung structure
v. ASTHMA ATTACKS
1. Terrifying because of difficulty in breathing
2. Airway obstruction due to:
a. Spasms of the bronchial tubes
b. Increased mucous secretion
c. Swelling of the mucous membranes
vi. ASTHMA CLASSIFICATION
1. Allergic or Atopic (extrinsic) – allergens
2. Nonallergic or Nonatopic (intrinsic) – stress, fatigue, etc.
vii. Prevalence of asthma classified as allergic (extrinsic) in:
1. < 12 y/o: 90%
2. < 30 y/o: 70%
3. > 20 y/o: 50%
viii. Asthma due to specific environmental exposures or exercise may disappear during adulthood
ix. Many people fall under BOTH asthma classifications
x. ALLERGIC/ATOPIC (EXTRINSIC) ASTHMA
1. Allergens  immune system  abnormal amounts of IgE and IgG antibody production 
binds to the mast cells
2. Following subsequent allergen exposure and IgE and IgG binding, the mast cells release 
histamine, leukotrienes, and prostaglandins  asthmatic response
3. Respond positively to skin tests for common allergens
4. ALLERGIC RESPONSE: the first time an allergy prone person runs across an allergen (such as
ragweed)  make large amounts of ragweed IgE antibody  these IgE molecules attach
themselves to mast cells  the second time the person interacts with ragweed, the IgE primed
mast cells release granules and powerful chemical mediators (histamine, cytokines) into the
environment  these chemical mediators cause the characteristic symptoms of allergies
5. In western countries, immune systems of babies are exposed to very few challenges
(vaccinations, clean water, air, food, antibiotics, etc.)
6. Immune system does not develop in a balanced way
a. T helper 1 cells (respond to pathogens) may not develop normally
7. Balance is tipped towards T helper 2 cells
a. T helper 2 cells (responsible for allergic response)  overreaction to allergens
xi. Exacerbations can be triggered by:
1. Respiratory infections
2. Exercise
3. Stress
4. Cold air
5. Tobacco smoke
6. Pollutants
7. Dust mites, cockroaches’ feces, animal dander, mold, mildew, pollen, ragweed, etc.
c. OCCUPATIONS AT RISK FOR ASTHMA
i. Animal handlers
ii. Chemical workers
iii. Coffee or tea workers
iv. Grain handlers
v. Carpenters
vi. Hair dressers
vii. Leather workers
viii. Green house workers; farmers
d. ASTHMA PREVENTION AND CONTROL
 i. Animal allergies
1. Remove animal from house or at least bedroom
ii. Dust mite allergies
1. Encase mattresses and pillowcases in airtight covers
2. Wash bedding every week in hot water
3. Remove carpets, drapes, etc.
4. Use HEPA filters
iii. Mold allergies
1. Frequent indoor cleaning and use of dehumidifiers
iv. Outdoor allergies
1. Remain indoors in air-conditioned environments on days with high pollen or pollutant
levels
2. Use HEPA filters
v. Avoid exposure to tobacco smoke
e. MEDICAL TREATMENT FOR ASTHMA
i. Antihistamines for allergies
ii. Inhaled anti-inflammatory agents: Cromolyn or corticosteroid inhalers
iii. Immunotherapy or desensitization
f. EFFECTIVENESS OF IMMUNOTHERAPY
i. Overall:
1. 1/3 are cured after treatment
2. 1/3 have partial relapse
3. 1/3 have complete relapse
ii. Sublingual immunotherapy
iii. 44 patients with allergic asthma randomized to immunotherapy shots (pollen) or placebo
1. Hay fever symptoms: decreased by 49% vs. 15%, respectively
2. Medication requirement: decreased by 80% vs 19%, respectively
3. Asthma symptoms: decreased by 90% vs. 11%, respectively
4. Quality of life – marked improvement in treatment group
IV. CYSTIC FIBROSIS
a. Kills more children than any other genetic disease
b. Life span: improved from 16 to 30+
c. More common in children of Central European ancestry and rare in Blacks
d. Autosomal recessive genetic disease of the secretory glands
i. Inherit 2 faulty genes from each parent
ii. Affects the glands that make mucus and sweat
e. Normal mucus is slippery and water; CF mucus is thick and sticky
f. Affects the lungs, pancreas, intestines, liver, sinuses, etc.
g. Mucus builds up in the lungs and blocks the airways making it easier for bacteria to grow  leads to
lung infections, coughing, and shortness of breath
h. Over time, infections can severely damage the lungs and cause collapsed lungs and emphysema
i. The mucus can also block the pancreatic duct, preventing enzymes from reaching the small intestine
j. Digestion and absorption of fats, proteins, and fat-soluble vitamins is affects
k. Bulky stools, intestinal gas, swollen belly, pain, and discomfort
l. Child doesn’t gain weight, despite good appetite
m. Lose a lot of sodium in the sweat; risk for dehydration
n. Heat intolerance is also a symptom of the disease
o. Bile ducts become obstructed  leading to liver cirrhosis with portal hypertension
p. Many have diabetes mellitus because of:
i. Insulin resistance
ii. Scars in the pancreas because of thick mucus that lead to less insulin production
q. High risk for osteoporosis
r. Infertility in both men and women:
 i. Absence of the vas deferens in men
ii. Thickened cervical mucus in women
iii. Malnutrition in women disrupts ovulation and causes amenorrhea
s. TREATMENT
i. Breathing exercises
ii. Respiratory PT to loosen the thickened mucus
iii. Oral pancreatic enzymes to offset enzyme deficiencies
iv. Extra salt on food and salt tablets in hot weather to combat electrolyte loss through sweating
v. Feeding tube at night
vi. Air conditioners and humidifiers help to decrease vulnerability to respiratory infections
vii. Medications:
1. Anti-inflammatory meds, antibiotics, mucus thinners
viii. Oxygen therapy is used as needed
ix. Education and emotional support

ARTHRITIS AND MUSCULOSKELETAL DISEASE

I. ARTHRITIS
a. About 54.4 million (22.7%) adult in the US have reported being told by a doctor that they have some
form of arthritis
b. About 50% of adults under 65 y/o: arthritis diagnosis
c. > 100 different forms of arthritis
i. Osteoarthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia
d. Arthritis = leading cause of disability in the US
e. Physical disability:
i. Some difficulty in performing one or more ADLs
II. OSTEOARTHRITIS
a. Epidemiology
i. > 30 million US adults
ii. Prevalence affected by:
1. Age, ethnicity, SES, defective collagen (component of cartilage) synthesis gene, gout,
rheumatoid arthritis
b. PATHOPHYSIOLOGY
i. Chronic progressive disease
ii. Deterioration of joint cartilage and bone
iii. Body responds by producing excess bone, which makes joint movement painful
iv. CLINICAL FEATURES: pain, tenderness, swelling, and decreased function
v. Tiny pieces of bone or cartilage can break off and float inside the joint space  causes more pain
and damage
vi. Joints of hips, knees, fingers, or toes most affected
c. RISK FACTORS
i. Obesity (leading risk factor)
1. Weight loss decreases risk of knee and hip osteoarthritis
ii. Repetitive joint usage
1. Job requiring knee bending wile lifting heavy items  knee osteoarthritis
2. Basketball, soccer, football, baseball pitchers  osteoarthritis
iii. Joint trauma
iv. Defect in how the bones forming joints fit together (ex: bowlegs)
d. PREVENTION
i. Avoid obesity
ii. Avoid joint trauma
iii. Minimizing occupational-related joint stress through ergonomic approaches
1. Ex: setting up keyboards at the right height to prevent wrist injuries
iv. Braces or shoe inserts to reduce joint stress
e. DIAGNOSIS
i. X-rays
ii. CT scans
iii. MRI
iv. ARTHROCENTESIS
1. Needle with syringe to collect synovial fluid
2. Detects inflammation, infection, uric acid crystals, uric acid levels
v. ARTHROSCOPY
1. A lighted optic tube (arthroscope) is inserted into the joint and arthroscopic procedures can
be performed (ex: removal of torn cartilages)
f. TREATMENT
i. Lose excess weight – decreases pain
ii. Physical therapy
1. Maintain and improve joint ROM
2. Maintain and improve muscle strength
iii. Occupational therapy
1. Maximize the patient’s independent ability to perform ADLs
iv. Low impact exercise:
1. Tai chi, swimming, etc.
2. Decrease pain
3. Increase lower body muscle strength and flexibility + functioning of the joint
v. Manage stress
vi. Diet:
1. Follow nutritious diet
2. Vitamin D supplements of 400-800 IU may halt progression of joint damage
g. DRUG TREATMENT
i. Acetaminophen (Tylenol) and capsaicin cream
1. Both help with pain but capsaicin also helps with inflammation
ii. NSAIDs – aspirin, Ibuprofen (Advil), naproxen
1. Helps with pain and inflammation
2. Combine with stomach protecting meds if you have had ulcers or GI bleeding
iii. COX II inhibitors (Celebrex) – also NSAIDs
1. Cause less stomach irritation from aspirin or ibuprofen
2. Block cyclooxygenase (enzyme) that is believed to trigger pain and inflammation
3. COX II inhibitors associated with CVD
a. Suppresses cation of prostacyclin (PG12)  hormone that dilates blood vessels and
reduced blood clotting
iv. Steroids
1. Major side effects
a. Hyperglycemia
b. HTN
c. Impaired lipid profile (increased TG)
d. Glaucoma  blindness
e. Bone resorption (osteoporosis)
h. ALTERNATIVE THERAPY
i. Glucosamine (amino sugar) – glucose + amino acid
1. From shellfish  Believed to cause cartilage formation and repair
ii. Chondroitin sulfate
1. From shark cartilage  believed to give cartilage elasticity
i. GLUCOSAMINE AND CHONDROITIN SULPHATE IN PAINFUL KNEE OSTEOARTHRITIS
i. Randomized patients with symptomatic knee osteoarthritis for 24 weeks to:
1. 1500 mg/d glucosamine
 2. 1200 mg/d chondroitin sulfate

3. Both glucosamine + chondroitin sulfate

4. Placebo

ii. None of the supplements reduced pain; showed no improvement

j. SURGERY – TOTAL JOINT REPLACEMENT
i. If patient has severe pain and/or limitation of physical activity + fails to respond to drugs
ii. Damaged joint is replaced by a prothesis (plastic, metal, or both)
III. RHEUMATOID ARTHRITIS (RA)
a. Chronic inflammation – autoimmune disease
b. Inflammation begins at the synovial membranes of the joints
c. Inflammation spreads to other joint tissues
d. Inflamed tissue may invade and damage the cartilage in the joints and erode  leads to joint
deformities
e. CLINICAL SYMPTOMS:
i. Stiffness, pain, and swelling of multiple joints
ii. Fatigue
iii. Anemia (inflammation and Fe absorption and recycling)
f. Small joints are more likely to be affected (hands, wrists)
g. EPIDEMIOLOGY
i. 1% of US adults
ii. Prevalence increases with age
iii. 2-3x greater in females vs. males
iv. 4x higher in Native American vs. whites
v. Asians have lower prevalence rates than whites
h. RISK FACTORS
i. Human leukocyte antigens genes (HLA) defect
1. HLA genes help to detect body’s own proteins from foreign invaders
2. Defect in HLA genes  leads to RA
ii. Changes in sex hormones (esp. in women)
1. RA goes into remission during pregnancy
2. Higher risk during menopause
iii. Environment
1. Viral or bacterial infections
2. Smoking
3. Air pollution
4. Insecticides
5. Occupational exposures to mineral oil (by-product of refining crude oil_ and silica (rock
drilling or stone crushing)
i. DIAGNOSIS
i. X-ray
ii. MRI
iii. Autoantibodies (antibodies against own tissues)
1. High levels of rheumatoid factor
2. High levels of anti-cyclic citrullinated peptide (anti-CCP) antibodies
j. DRUG TREATMENT
i. First choice: aspirin, ibuprofen (advil), naproxen, capsaicin cream
1. Combine ibuprofen with stomach protecting meds if you’ve had ulcers or GI bleeding
ii. Second choice:
1. Corticosteroids (prednisone)
2. Immunosuppressants:
 3. Older drugs
a. Gold compounds (reduces inflammation)
b. Methotrexate (prevents structural joint damage)
iii. Alternative therapies to decrease inflammation:
1. Fish oil supplements
2. Flax seed oil
3. Gamma-linolenic acid (evening primrose)
4. Curcumin (found in turmeric)
iv. Flu shots  excess mortality from respiratory and infectious diseases
v. Good diet, low impact exercise, and stress management
IV. GOUT
a. Type of arthritis – affects joints of the feet, esp. big toes
b. Sometimes affects joints of the hand, fingers, wrist, or knee
c. Affects 3 million people in the US
d. PATHOGENESIS
i. Excess uric acid in the blood
1. Body makes too much uric acid OR has a hard time reducing uric acid
ii. Too much uric acid in the fluid around the joints (synovial fluid) can lead to uric acid crystals
iii. These crystals cause the joint to swell up and become inflamed
e. SYMPTOMS
i. Sudden onset
ii. Joint will be warm, red, tender, and painful
iii. May have a fever
iv. The attack may go away in several days
v. May return from time to time
vi. Some people may develop:
1. Chronic gouty arthritis
2. Uric acid kidney stones  can cause kidney failure
f. HIGH RISK GROUP
i. Family history
ii. Male
iii. Postmenopausal women
iv. Red meat, alcohol, organ meats, sea food, some types of fish (sardines)
v. Purines  precursors to make uric acid
vi. Medications – hydrochlorothiazide (diuretic)
1. Interferes with removal of uric acid
vii. Conditions – diabetes, kidney disease, obesity, sickle cell anemia, leukemia
g. DIAGNOSIS
i. Aspirated joint fluid will show uric acid crystals
ii. Uric acid levels in the blood and urine
iii. Joint x-rays
h. TREATMENT
i. NSAIDs like ibuprofen
ii. Colchicine to reduce pain, swelling, and inflammation
iii. Stronger painkillers (codeine, hydrocodone, oxycodone)
iv. Corticosteroids injections into the joint
v. Allopurinol or probenecid to decrease uric acid levels in the blood
vi. Limit intake of alcohol, red meat, organ meats, certain fish (cod, herring, sardines, mackerel,
anchovies, haddock, tuna) and sea food (shrimp, lobster, scallops)
vii. Include plant proteins
viii. Include low fat dairy
1. Less purines
2. Contain casein and lactoalbumin
 ix. If you’re losing weight, lose it slowly to prevent kidney stone formation
V. OSTEOPOROSIS
a. Decreased bone mass to the extent that fractures occur with minimal or trivial trauma
b. Osteoporosis affects 20 million people in the US
c. Associated with 1.5 million fractures per year
d. Clinical manifestations: fractures of the spine, hip, wrist
e. Bone development and loss
i. Start bone loss around 30  bone loss accelerates with menopause (lasts 10-15 years)
f. Bone – type 1 collagen stiffened by crystals of Ca hydroxyapatite
g. Osteoblasts (bone building cells)
i. Secrete a collagen protein matrix  support structure
ii. Osteoblasts  osteocytes  secrete bone minerals  bone mineralization
1. As osteoblasts mature, they are converted into osteocytes
h. Osteoclasts (bone breakdown cells)
i. Secrete substances that lead to bone resorption
i. ESTROGEN DEFICIENCY  bone loss and loss of bone strength
i. Death of osteocytes (made by osteoblasts) by apoptosis
ii. Reducing the lifespan of osteoblasts
iii. Prolonging the lifespan of osteoclasts
1. More bone resorption
iv. Increasing the rate of remodeling = increased risk for fractures
1. More densely mineralized bone is replaced by younger, less densely mineralized bone
2. Excavated resorption sites remain temporarily unfilled
3. Impairs maturation of collagen
j. RISK FACTORS
i. Gender
1. 1/3-1/2 of all US women experience fractures associated with low bone mass
ii. Ethnicity
1. White vs. African-American women
a. African-American women AND men = lowest risk of osteoporosis/osteopenia of all
ethnicities
2. White women: 50% will suffer from osteoporotic fracture
3. Asian women
iii. Genes
1. ~80% of bone mass is determined by genetic disposition
iv. Surgical menopause with no exogenous estrogens
v. Inactivity
vi. Lean vs. obese – hormone; greater stimulus to bone
1. Excessively lean  less muscle activity on bone  more resorption
vii. Smoking  decreases estrogen production
1. Free radicals and chemical cause more bone resorption
viii. Stress
ix. Excessive drinking
x. Certain medications
xi. Anorexics
xii. Female athletes who aren’t menstruating
xiii. Poor diet
1. Low in calcium and vitamin D
2. High in phosphoric acid, caffeine, sodium, retinoids, alcohol, and protein intake
k. PREVENTION
i. DIET
1. Calcium (1,000-1,200 mg/d)
2. 300 mg rule
 3. Vitamin D needs
a. Adults up to 70 y/o = 15 g/d (600 IU/d)
b. Adults over 70 y/o = 20 g/d (800 IU/d)
c. Food sources/sunlight/supplements
4. Moderation in phosphoric acid, caffeine, sodium, retinoids, alcohol, and protein intake, esp.
when insufficient Ca and vitamin D consumed
5. Japanese vs. Americans
a. Plant foods (fruit, vegetables, nuts, seeds)
i. Potassium alkali, bicarbonate, gluconate, citrate
ii. Vitamin K, antioxidants, etc.
1. Vitamin K is needed for protein synthesis in the bones
b. Physical activity
c. Low intakes of meat
ii. Ca + Vitamin D Supplement and the Risk of Fractures (Jackson et al, NEJM 2006)
1. Women between 50-79 y/o randomized to either:
a. 1000 mg/d Ca + 800 IU/d vitamin D3
b. Placebo
2. 7-year follow up  Ca + vitamin D supplementations led to:
a. Small but significant increase in hip bone density
b. Did not significantly decrease hip fracture
c. Increased the risk of kidney stones by 17%
3. When data on women who adhered poorly were excluded  hip fractures risk was
significantly lower in the supplement group
4. Limitations:
a. Didn’t select women based on bone mass
b. More than 50% in both groups were receiving ERT
5. Conclusions: vitamin D supplement was not enough to ensure optimal bone health
iii. Meet exercise requirements
1. Weight bearing and resistance exercise
a. Bone mineralization
b. Muscular strength, balance, and flexibility
2. Tai chi
iv. Meet dietary needs
v. Not smoking
vi. Menstruate regularly (younger women)
vii. Manage stress
viii. Moderate alcohol
ix. DEXA:  65 y/o or at high risk for osteoporosis
l. DEXA: T-SCORE
i. Used in post-menopausal women and men > 50 y/o
ii. T-score  patient’s BMD vs. BMD of healthy 30 y/o controls of the same sex, ethnicity, and gender
iii. Osteoporosis: t-score = -2.5 or lower (at least 2.5 SDs below mean for controls)
iv. Osteopenia: t-score = -1 to -2.5
v. Normal: t-score = -1.0 or greater
m. DEXA: Z-SCORE
i. Used in premenopausal women and men under the age of 50 + children
ii. Number of SDs a patient’s BMD differs from the average BMD of their age, sex, and ethnicity
n. RISK FOR OSTEOPOROTIC FRACTURES IN THE NEXT 10 YEARS
i. FRAX online calculator
ii. Developed by WHO using the following factors:
1. Sex, weight, height, previous fracture, parent fractured hip, current smoking, glucocorticoids,
rheumatoid arthritis, alcohol intake, femoral neck BMD, etc.
2. Does not take into account diet and exercise
VI. DRUGS FOR OSTEOPOROSIS
a. ERT was used to preserve bone mass and decrease risk for CVD
i. WHI: post-menopausal women were randomized to ERT or placebo
1. ERT improved bone health but was linked to increased risk for CHD, stroke, breast cancer,
blood clots in lungs, Alzheimer’s disease, urinary incontinence, severe depression
2. Trials were halted
ii. Not used for osteoporosis
b. DRUGS TO SLOW BONE LOSS IN MENOPAUSAL WOMEN – all meds reduce bone resorption (prevent
bones from breaking down)
i. BISPHOSPHONATES
1. Reduces bone resorption
2. SIDE EFFECTS: bone, joint or muscle pain, nausea, difficulty swallowing, heart burn,
esophageal irritation, gastric ulcer
3. RARE SIDE EFFECTS: thigh bone fracture, osteonecrosis of the jaw
ii. SELECTIVE ESTROGEN RECEPTOR MODULATORS
1. Binds with estrogen receptors on the bones and reduces bone resorption and increases bone
building.
2. COMMON SIDE EFFECT: hot flashes
3. RARE SIDE EFFECT: deep vein thrombosis
iii. CALCITONIN
1. Synthetic hormone
2. Reduces bone resorption
3. COMMON SIDE EFFECTSL runny nose, headache, back pain, nosebleed
4. Injected drug may cause flushing, nausea, skin rash, urinary frequency
iv. DENOSUMAB (PROLIA)
1. Reduces bone resorption
2. SIDE EFFECTS: reduces Ca in blood (spasms, cramps), weakens immune system, skin rashes
v. Drug benefits most when Ca and vitamin D needs are met
c. PHYTOESTROGENS AND BONE HEALTH
i. Osteoporosis risk in Japanese vs. American women
ii. May be due to high consumption of soy foods
1. Phytoestrogens (isoflavones) – plant-based estrogen
2. Soy proteins  less urinary calcium loss than animal protein
iii. Phytoestrogens may improve bone health and decrease certain fractures in American women
iv. Needs to be confirmed by further studies

CHRONIC NEUROLOGICAL DISORDERS

I. ALZHEIMER’S DISEASE (AD)
a. Irreversible progressive brain disease that slowly destroys memory and thinking skills
b. Destruction of neurons  decrease in ACh (NT) levels  deterioration in communication among
brain parts
c. Neurons become filled with tangles of TAU PROTEINS
d. Space between neurons are filled with BETA-AMYLOID PLAQUES (proteins)
e. TAU
i. Healthy neurons have a cytoskeleton made up of microtubules
ii. MICROTUBULES allow nutrients, molecules, etc. to move from the cell to the ends of the axon and
back
iii. Tau protein makes the microtubules stable through phosphorylation
iv. In AD – tau becomes hyperphosphorylated  hyperphosphorylated tau pairs get tangled up with
each other  microtubules disintegrate  problems in communication between neurons and
death of the cells
f. BETA-AMYLOID PLAQUES
 i. Amyloid precursor protein (APP)  transmembrane protein that sticks through the neuron
membrane and helps neurons grow and repair
ii. APP is snipped into fragments of protein, including beta-amyloid
iii. Beta-amyloid  controls signaling between cells
1. AD patients don’t clear beta-amyloid fast
2. Beta-amyloid fragments come together in clumps to form plaques
3. Plaques disrupts the work of neurons
iv. Affects memory
g. EPIDEMIOLOGY
i. AD affects 5.7 million Americans.
ii. Prevalence is expected to rise.
iii. Age at diagnosis is generally about 75 years.
iv. 1 in 8 Americans over 65 have AD
v. 70% are cared for at home
vi. Cost from AD and other dementias is $226 billion/yr:
1. Medical expenses; Lost productivity
h. SYMPTOMS
i. INITIAL: forgetfulness, difficulty concentrating, performing familiar tasks
ii. PROGRESSION: severe memory loss (esp. for recent events), depression, anxiety
iii. LATER STAGES:
1. Disorientation and possible hallucination
2. May become very aggressive or docile
3. Eventually lose control of physical functioning and are completely dependent on
caregivers
iv. Within 5-10 years of diagnosis – patient becomes disabled, immobile, and muted
v. Usually die of pneumonia
i. RISK FACTORS
i. Age
ii. Inheritance of Apo E-4 gene – affects neuron development
1. One copy of Apo E04 gene  3-5x greater risk for AD than control
2. Two copies of Apo E-4 gene  15x greater risk of AD than control
3. E-2 and E-3 gene variants do NOT cause AD
iii. Early onset AD
1. Amyloid precursor protein (APP) gene mutation
2. Presenilin 1 or 2 (PSEN 1 or 2) gene mutation  affects APP processing
iv. Genes only play a small role in the development of AD
v. Low SES
vi. Physical inactivity
vii. Head trauma (football players)
viii. Aluminum in drinking water
ix. Estrogen replacement therapy
x. Homocysteine
xi. Transient ischemic attacks
xii. Atherosclerosis
xiii. Hypertension Leads to inflammation
xiv. Hyperinsulinemia
1. Inflammation in the brain
2. Increases amyloid plaque
j. AD – PREVENTION
i. Exercising the mind
1. Reading, crossword puzzles, playing an instrument, board games, being creative
ii. NSAIDS (decrease inflammation)
iii. Increase physical activity
 iv. Diet
1. Fruits, vegetables, legumes, nuts, vegetable oils, seeds
a. Antioxidants neutralize free radicals that damage nerve cells; vit E may be most
beneficial
2. Folate, B-6, and B12 supplements (not proven)
a. RCTs show that B vitamins decreases homocysteine
3. Omega-3 fatty acids supplements (not proven)
4. Mediterranean type of diet may be protective
v. PHYSICAL ACTIVITY
1. Abbott et al, JAMA, 2004
a. Physically capable men 71-93 in the Honolulu Asian Aging study
b. Assessed distance walked/day from 1991-1993
c. Incidence of dementia was assessed in 1994-1996 and 1997-1999
d. Men who walked < 0.25 miles/day had 1.8x excess risk for dementia than men who
walked > 2 miles/day
2. Weuve et al, JAMA, 2004
a. 18766 women aged 70-81
b. Regular PA, including walking, is associated with better cognitive function and less
cognitive decline
3. Lautenschlager et al, JAMA 2008
a. Randomized older people (over 50) with memory problems but not dementia to 6
months of:
i. Exercise (10,000 steps/day)
ii. Control
b. 18-moth follow
c. Exercise group showed a mean improvement in cognitive function vs. controls
d. LIMITATION  not known if older people with more physical limitations are able to
do the exercise
4. Farina et al, 2014
a. Meta-analysis – included 6 RCTs on the effect of exercise on cognitive outcomes in AD
patients
b. Exercise generally had a positive effect on cognitive decline in AD patients
vi. High Dose B-Vitamin Supplements – Aisen et al, JAMA 2008
1. Double blind RCT – randomized 409 individuals with mild or moderate AD for 18 months
to either:
a. High doses of folate (5 mg/d), vitamin B6 (25 mg/d), and B12 (1 mg/d)
b. Placebo
2. Supplements lowered homocysteine levels as expected but did not slow cognitive decline
in the supplement group compared to the placebo group
vii. DHA Supplementation
1. DHA (omega-3 fatty acid) = most prominent fatty acid in the brain
2. DHA levels in the brain are much lower in patients with AD vs. those without AD
3. Quinn et al, 2010
a. 402 mild or moderate AD patients randomized for 18 months to:
i. 2 g DHA or placebo
b. DHA supplementation did not slow down the rate of cognitive or functional decline
viii. STATINS
1. May lower AD risk bc:
a. It lowers serum cholesterol
b. Lowers inflammation
c. Reduces neurodegradation in AD
i. Statins help prevent the breakdown of nerve cells
2. Cholesterol is associated with AD
 a. High cholesterol = plaque build-up (even in the brain)
k. AD – DIAGNOSIS
i. Blood test (genetic predisposition) – Apo E4 gene
ii. Pencil-and-paper test to evaluate memory and mental functions
1. Very extensive in evaluating memory and mental functions
iii. Brain scans
iv. Examination of brain tissue during an autopsy
1. Gold standard
l. EARLY DETECTION
i. Positron emission tomography (PET scan)
1. Intravenous injection of fluorodeoxyglucose
a. Glucose with radioisotope fluorin-18
2. Uptake of this substance is detected by the PET scan
3. Detects amyloid plaques
4. Expensive and exposure to some radiation
5. 1/3rd of elderly have these plaques but function normally
ii. Spinal fluid tap
1. Assesses tau protein tangles and beta amyloid plaques
2. Expensive, painful, and risk of injury or infection
3. False positives
iii. Even if tests detect early AD, there is no therapeutic avenue.
iv. Early detection may cause emotional trauma
m. TREATMENT
i. Create safe environment to prevent wandering off or forgetting about food on the stove
ii. Establish routine
iii. Regular physical activity
iv. Calming conversations
v. Music therapy  may help with memory recall, pain, sense of control, less discomfort, and
emotional intimacy
vi. Diet
1. Healthy diet and management of body weight
2. Frequent small meals and nutrient-dense snack using favorite foods to encourage regular
eating
3. Vitamin E (900 mg twice a day)  may slow progression of AD
vii. Medication
1. Donepezil, rivastigmine, or galantamine
a. Inhibits breakdown of ACh
b. Slows progression of the disease
c. Drug effect is minor, short-lived
d. Significant side effects
2. Memantine
a. Slows decline in mental function
3. Antidepressants
II. PARKINSON’S DISEASE (PD)
a. Neurodegenerative disorder
b. Annual incidence = 20/100,000
c. Loss of the melanin-containing neurons in the brain  reduction in dopamine/other NTs
d. Without dopamine, nerve cells can’t send messages  loss of muscle function
e. Symptoms may be mild at first
i. Slight tremor or feeling that one leg or foot is dragging
f. Characterized by resting tremor, muscular rigidity, postural instability, and slowness in the initiation
and execution of movement (bradykinesia)
g. SIGNS/SYMPTOMS:
 i. Automatic movement (e.g. blinking) slows/stops, difficulty swallowing, drooling, mask like
expression in the face, muscle aches and pains, constipation, loss of appetite, headache, visual
degeneration, leg cramps, monotone speech, loss of small or fine hand movements, anxiety, etc.

ii. The disease course is progressive and often severely limits functional abilities.

h. EPIDEMIOLOGY

i. Onset usually after age 50.

ii. Highest incidence rates between ages 75 and 84.
iii. Family history is a risk factor
iv. Men are more likely to develop PD than women.
v. More common among Caucasians than Blacks
vi. Pesticides and smoking are risk factors

i. TREATMENT

i. Good nutrition

ii. Exercising, but adjusting the activity level

iii. Avoiding stress

iv. PT, speech therapy, and OT

1. Heat and massage therapy

2. Railing or banisters placed in commonly used areas

3. Special eating utensils

v. Support groups

vi. Deep brain stimulation by implanting electrodes in certain parts of the brain

1. Patient turns on/off the implanted pulse generator in color bone by passing a magnet over
it

vii. Destroy brain tissue that cause the symptoms

viii. EXERCISE – TANDEM CYCLING IN PD PATIENTS

1. Improved motor function by 30%

2. Reduced rigidity and tremor

3. Reduced bradykinesia

4. Improved flexibility and balance

5. Improved bladder and bowel function

ix. DRUGS TO IMPROVE BRADYKINESIA AND POSTURAL IMBALANCE

1. Dopamine replacement therapy – levodopa and carbidopa

a. Levodopa converted to dopamine (levodopa = precursor for dopamine)

b. Carbidopa slows breakdown of levodopa

2. Dopamine agonists  mimic the action of dopamine

a. Pramipexole, Ropinerole, Bromocriptine

3. MAO-inhibitors

a. Used alone or in combination with Levodopa/Carbidopa

b. Inhibits an enzyme that breaks down Levodopa

c. Selegiline, Rasagilene
4. COMT-inhibitors
a. Used alone or in combination with Levodopa/Carbidopa
b. Allows a larger amount of Levodopa to reach the brain
c. Entacapone, Tolcapone
BLOOD PRESSURE
1. Define SBP and DBP
a. Systolic = pressure in arteries when the heart pumps
b. Diastolic = pressure in the arteries when the heart is filling
2. Define the classification of BP
a. OLD GUIDELINES OF BP
i. Normal: SBP < 120 and DBP < 80 mmHg
ii. Prehypertension: SBP 120-129 or 80-89 mmHg
1. Not normal
2. All most positive that you will get hypertension
iii. Hypertension:
1. SBP ≥ 140 or DBP ≥ or on antihypertensive medications
2. Stage 1 HTN: SBP 140-159 or DBP 90-99 mmHg
3. Stage 2 HTN: SBP ≥ 160 or DBP ≥ 100 mmHg
b. New Guidelines of BP
i. Created by ACC (American College of Cardiology) and AHA (American Heart Association) –
2017
ii. More stringent diagnosis criteria because even at lower BP, you have a good chance of CVD
iii. Normal: SBP < 120 and DBP < 80 mmHg
iv. Prehypertension: SBP 120-129 and DBP < 80 mmHg
v. Hypertension: SBP ≥ 130 or DBP ≥ 80 or on antihypertensive medications
1. Stage 1 HTN: SBP
2. Stage 2 HTN:
3. Define the impact of BP on CVD
a. HTN AND CVD RISK
i. Silent disorder
ii. Independent risk factor for CVD
iii. CVD risk begins at 115/75 and doubles with each 20/10 mmHg increment
1. Strong relationship: risk for CVD begins when you are in “normal” range
2. As risk for HTN increases, risk for CVD increases as well
iv. 1/3 of BP-related deaths from coronary heart disease occurs in prehypertensives
b. CUMULATIVE INCIDENCE OF CVD EVENTS
i. People who had normal BP/elevated BP/stage 1 HTN/stage 2 HTN – followed over time
1. All groups have a risk for CVD events
2. People with elevated BP have a higher risk for CVD events than normal BP
c. CUMULATIVE INCIDENCE OF ALL CAUSE MORTALITY
d. FACTORS FOR SIGNIFICANCE OF HTN
i. [HTN CAN CAUSE CVD & CVD CAN CAUSE HTN]
ii. Heart disease
1. Plaque causes many issues
iii. Stroke (ischemic and hemorrhagic)
1. bleeding of the brain; weak blood vessels  ruptured  hemorrhagic stoke
2. blood clot; vessels of arteries going to the brain get damaged  blockage in artery 
plaque adds to clot  ischemic stroke
iv. Cognitive function
1. blocking/reducing blood to the brain
v. Peripheral artery disease
1. Blockages in arms and legs
2. Leads to plaque formation
vi. Kidney damage
1. Damages blood vessels in the kidneys  kidneys have trouble filtering waste
2. Hypertensive neuropathy
vii. Vision problems
 1. Damages blood vessels going to the eyes  retinopathy
viii. Disability due to stroke
ix. Sudden cardiac death
x. Treatment  decrease risk of complications
4. Describe the prevalence of HTN and pre-HTN in US adults and the risk for HTN by age, race, obesity,
and region
a. PREVALENCE OF HYPERTENSION AMONG ADULTS – NHANES (2015,2016)
i. Hypertension: 29%
ii. Pre-hypertension: 28.0% (2005-2006)
1. ~60% of US adult population is hypertensive or prehypertensive
2. If they are prehypertensive, the will most likely become hypertensive
iii. Disproportional rates among:
1. Non-Hispanic blacks (40.3%)
2. Over 60 years old (63.1%)
3. Obese individuals (40.5)
a. All of these rates are higher than general population
b. GEOGRAPHIC DISTRIBUTION
i. Southeastern states (“Stroke Belt”)
1. STATES:
a. Alabama
b. Arkansas
c. Georgia
d. Indiana
e. Kentucky
f. Louisiana
g. Mississippi
h. North Carolina
i. South Carolina
j. Tennessee
k. Virginia
ii. These states have highest rates of HTN and CVD
iii. Especially among African Americans
c. TRENDS IN HTN
i. TIME TRENDS  from 1960 to 2012, distribution of BP has shifted to lower BP
ii. Shifted to the left (lower values)
1. More people are become aware of their BP
2. More people are getting treated for HTN
3. More people are controlling their BP
iii. Across all age groups, the prevalence of HTN/uncontrolled BP have decreased
1. Fewer people with uncontrolled HTN now than in the 1960s
d. AGE
i. Partly due to high blood cholesterol
1. Atherosclerosis  plaque build up
ii. As plaque builds from cholesterol, arteries become rigid and less flexible
1. Harder to dilate and constrict
iii. Industrialized society vs. developing countries
1. Industrialized = rise in BP as you get older
2. Developing = BP stays consistent as you get older
3. DUE TO:
a. Diet (developing countries are mostly plant-based; industrialized diets are
more animal-based)
b. Exercise (lack of physical activity)
 c. Excess body fat (developing countries have more lean population;
industrialized have more excess body fat)
e. AFRICAN AMERICANS
i. Prevalence
ii. Get HTN at earlier age
iii. More complications
1. Eye diseases, stroke
5. Describe the awareness, treatment, and control of HTN among hypertensive individuals
i. NHANES, 2011-2012
ii. 17% were not aware of their HTN
1. HTN is a silent disorder
iii. 24% were not being treated for HTN
iv. Only 48% controlled their HTN
6. Discuss why BP doesn’t raise as much with age in individuals in developing countries compared to
developed countries
a. Industrialized society vs. developing countries
i. Industrialized = rise in BP as you get older
ii. Developing = BP stays consistent as you get older
iii. DUE TO:
1. Diet (developing countries are mostly plant-based; industrialized diets are more
animal-based)
2. Exercise (lack of physical activity)
3. Excess body fat (developing countries have more lean population; industrialized
have more excess body fat)
7. Explain why HTN is called a “silent disorder” and how it leads to health problems
a. HTN AND CVD RISK
i. Silent disorder
ii. 17% were not aware of their HTN
iii. Independent risk factor for CVD
iv. CVD risk begins at 115/75 and doubles with each 20/10 mmHg increment
1. Strong relationship: risk for CVD begins when you are in “normal” range
2. As risk for HTN increases, risk for CVD increases as well
v. 1/3 of BP-related deaths from coronary heart disease occurs in prehypertensives
8. Describe the 4 major modifiable factors related to BP, the order of importance, and the mechanisms
by which they lower BP
a. Smoking
b. ESTABLISHED FACTORS:
i. Body weight (1st most important)
ii. Physical activity (2nd)
iii. Alcohol intake (3rd)
iv. Sodium intake (4th)
c. K, Mg, Ca, Dietary fiber, cholesterol, fat, saturated fat, and protein
i. Positive  K, Mg, Ca, dietary fiber
ii. Negative  cholesterol, fat, saturated fat, protein
d. SMOKING AND BP
i. MECHANISMS
1. Damages endothelial lining
a. Plaque formation  stiff arteries  HTN
2. Increase peripheral vascular resistance
a. Difficult for blood vessels to dilate
3. Activates SNS (fight or flight)
e. BODY WEIGHT AND BP
i. Meta-analysis (effect of weight loss on BP)
 1. 25 RCTs (n=4874)
2. Mean duration: 66.6 weeks
3. 5.1 kg weight loss (diet/exercise/both)  -4.44/-3.57 mmHg (sys/dia)
4. ~ 1 mmHg reduction in BP per kg of weight loss
f. HOW DOES OBESITY INCREASE BP?
i. Overweight people have 2x greater risk of HTN than lean
ii. MECHANISMS:
1. Obesity  increases work by the heart
2. Obesity  insulin resistance  hyperinsulinemia  increase SNS activity 
increases HR, cardiac output, peripheral vascular resistance, and Na retention by
kidneys  increase BP
a. 65% of people with type 2 diabetes have HTN
b. INSULIN RESISTANCE  cells don’t respond to insulin  body produces
more insulin  increase sodium retention  sodium goes back into the
blood stream (not excreted in urine)  body retains more water to maintain
balance  increase BP  arterial damage
3. Obesity  increases activity of the RAA system
iii. Weight loss of 10-15 lbs.
1. Often treats BP or decreases need for drugs
2. Drug side effects:
a. Headaches
b. Impotence
c. Reduced exercise tolerance
d. Persistent cough
g. PHYSICAL ACTIVITY AND BP
i. Meta-analysis – 15 randomized controlled trials with 633 subjects
ii. Ambulatory BP
iii. Training: 4 or more weeks
iv. Endurance exercise = -3.2/-2.7 mmHg
h. HOW DOES PHYSICAL ACTIVITY DECREASE BP?
i. Body weight
ii. Arterial flexibility
iii. Increases stroke volume  decreases resting HR and BP
i. ALCOHOL AND BP
i. Effect of alcohol reduction on BP
ii. Meta-analysis – 15 randomized controlled trials (n = 2234)
iii. Duration: < 4 to > 12 weeks
iv. Reduced number of drinks from 3-6/day to 1-2/day
v. Average reduction = -3.31/-2.04 mmHg
j. HOW DOES ALCOHOL INCREASE BP
i. Accounts for 10% of all cases of HTN
ii. MECHANISMS:
1. Stimulation of SNS
2. Inhibition of vascular relaxing substances
3. Ca and Mg depletion
iii. Limit to 2 drinks/day for men and 1 drink/day for women
k. SODIUM AND BP
i. INTERSALT Study
1. Cross-sectional study – 10,000 individuals aged 20-59 – 52 population samples form
32 countries
2. Primary finding  positive relationship between urinary Na excretion and BP
3. Secondary finding  BP increased with age (except in populations where salt intake
was low
 4. 2003-2011
a. 15% reduction in sodium intake
b. 40% reduction in deaths from heart attacks
c. 42% reduction in death from stroke
ii. Meta-analysis (EFFECT OF NA REDUCTION ON BP)
1. Randomized controlled trials – 34 studies with 3230 participants
2. Measured urinary sodium excretion
3. A reduction of 4.4 g/day salt intake  -4.18/-2.06 mmHg
4. Higher reductions among hypertensives
l. HOW DOES NA INCREASE BP?
i. Excess Na intake reduces ability of kidneys to excrete water
ii. Excess salt intake increases BP in salt sensitive people
1. African-Americans, older people, diabetics
iii. Treatment:
1. Sodium restriction
2. Diuretics (to increase urine output)
9. Discuss the relationship between vegetarianism and BP and the age-related rise in BP in vegetarians
vs. non-vegetarians
a. Vegetarians vs. non-vegetarians
i. BP tends to be lower in vegetarians
ii. Age related rise in BP
iii. Replacing animal foods with plant foods
b. What are the aspects of a vegetarian diet that may reduce BP?
i. High in fiber, potassium, and magnesium
ii. Low in fat, saturated fat, and cholesterol content
10. Identify the other modifiable risk factors that may be related to BP and explain the discrepancy
between the observational trials and the randomized trials with regards to these nutrients
a. OTHER DIETARY FACTORS AND BP
i. Vegetarians vs. non-vegetarians
1. BP tends to be lower in vegetarians
2. Age related rise in BP
3. Replacing animal foods with plant foods
ii. What are the aspects of a vegetarian diet that may reduce BP?
1. High in fiber, potassium, and magnesium
2. Low in fat, saturated fat, and cholesterol content
iii. Other observational studies:
1. Diets high in K, Ca, Mg, dietary fiber, and protein (esp. plant protein) are inversely
related to BP
2. May be independent of the establish risk factors
iv. Randomized trials:
1. Above nutrients given as dietary supplements  small and/or inconsistent effect on
BP
11. Describe the DASH study, the DASH-Sodium study, and the Premier Intervention study; include the
study design, diets (including specific nutrients modified), and the effect on BP; explain the results
THE DIETARY APPROACHES TO STOP HYPERTENSION (DASH) TRIAL
a. OBJECTIVE: effect of dietary patterns on BP
b. Potassium, magnesium, fiber, and calcium; low in fat, saturated fat, and cholesterol
c. SUBJECTS:
i. N = 459
ii. 49% women and 60% black
iii. Excluded people with stage 2 HTN
d. Fed a control diet for 3 weeks and then randomized for 8 weeks to:
 i. Control diet (low in fruits and vegetables, low in calcium, high in fat and saturated fats and
cholesterol)
ii. Fruits and vegetables rich diet
iii. Combination (DASH) diet
1. Rich in fruits and vegetables
2. Included low-fat dairy
3. Low in saturated and total fat and cholesterol
iv. NUTRIENT TARGETS
1. “fruits and vegetables” was similar to control group except it was rich in fruits and
vegetables
2. Increase in fiber and potassium from fruits and vegetables
3. Magnesium increase from legumes and nuts
4. Calcium increase from milk and nuts
e. All meals were provided
f. Controlled:
i. Body weight
ii. Sodium intake (no more than 3 grams/day)
iii. Alcohol no more than 1-2 drinks/day
g. Reductions seen in DASH diet are the same as results that would be observed in single drug therapy
i. Fruits and vegetable rich diet vs. control diet
1. All subjects: -2.8/-1.1 mmHg
ii. DASH diet vs. control diet
1. All subjects: -5.5/-3.0mmHg

2. Hypertensives: -11.4/-5.5 mm Hg

3. Normotensives: -3.5/-2.1mmHg

4. Minorities: -6.8/-3.5mmHg

5. Non-minorities: -3.0/-2.0mmHg
iii. Hypertensives
1. DASH diet vs. drug monotherapy for mild hypertension
DASH – SODIUM TRIAL
h. OBJECTIVE:
i. Effect of different levels of sodium + DASH diet on BP
1. Average Na intake (3.5 g/day)
2. Upper limit (2.3 g/day)
3. Adequate intake (1.5 g/day)
i. Randomized 412 subjects (> 50% female and >50% black) with BP > 120/80 mmHg
i. Control (typical American) diet
ii. DASH (combination) diet
j. Within the assigned diet, subjects consumed different levels of Na for 30 days each in a random
order:
i. High  2.5 g/day Na
ii. Intermediate  2.3 g/day Na
iii. Low  1.5 g/day Na
k. RCT parallel first, then the high/medium/low was the crossover portion
l. All meals provided
m. Weight kept constant
n. Regardless of diet type, reducing sodium will help BP
i. Lunch meat, hot dogs, breakfast sausage, fast food restaurants, frozen prepared meals,
canned vegetables, processed snacks
PREMIER STUDY
o. OBJECTIVE: effect of simultaneous implementation of all the lifestyle factors to reduce BP
i. Body weight, physical activity, alcohol intake, Na intake, DASH diet
p. Randomized 4-center trial – 810 subjects
i. 62% women; 34% African-American
ii. Excluded subjects with stage 2 HTN
iii. Not on hypertensive medications
iv. Mean age: 50 ± 8.9 years
q. INTERVENTION:
i. Advice only intervention
ii. Established intervention
iii. Establish + DASH intervention
r. Advice Only Intervention
i. 30 min individual session + printed material
ii. Printed material  weight, Na intake, physical activity, alcohol intake, DASH diet
s. Established Intervention (counseled frequently)
i. Weight loss of at least 15 lbs. at 6 months if overweight
ii.  180 min/week of moderate intensity physical activity
iii. Limit alcohol to 2 drinks/day (men) and 1 drink/day (women)
iv. No more that 2.3 g Na/day
v. Reduce saturated fat to  10% and total fat to  30% of energy
t. Establish + DASH Intervention (counseled frequently)
i. Established intervention recommendations
ii. 9-12 servings/day of fruits and vegetables
1. 4700 mg/day of magnesium (recommended amount) is 8-10 servings of fruits and
vegetables
iii. 2-3 servings/day of low-fat dairy products
iv. Further reduce saturated fat to  7% and total fat to  25% of energy
u. Subjects required to make their own food
v. 6-month period
i. Ask people to make fewer choices at a time, doing it all at once is too overwhelming (people
will get overwhelmed and quit)
w. Established vs. Established + DASH
i. Inadequate “dose” of fruits and vegetables
1. 4.8 servings/day  7.8 servings/day
ii. Complex intervention led to reduced adherence
12. Describe the results from the meta-analysis by Shah et al. studying the impact of diets of varying
macronutrient composition on BP and the possible mechanism
a. How does a high-carb diet increase BP and HR?
i. Insulin values are higher on the high carb diet than on the high mono-unsaturated fat diet
b. HYPERINSULINEMIA  increase SNS activity  increase HR, CO, vascular resistance, and Na +
water retention  increase BP
c. LIFESTYLE MODIFICATIONS – from RCTs
MODIFICATION ~ SBP REDUCTION
Weight Reduction 5-20 mmHg
Adopt DASH Diet 8-14 mmHg
Physical Activity 4-9 mmHg
Na Reduction 2.8 mmHg
Limit Alcohol 2.4 mmHg
i. CVD is more correlated with SBP
ii. As you get older, SBP increases more than DBP
iii. Much harder to decrease SBP
 d. AHA DIET RECOMMENDATIONS TO LOWER BP
i. Attain/maintain a BMI < 25 kg/m^2
ii. Lower sodium intake to 1.5 g/day
1. Processed foods
iii. Follow DASH diet
iv. Increase potassium intake to 4.7 g/day
1. DASH diet
2. Contraindicated in kidney disease patients  can’t excrete the potassium 
accumulates in the body (toxic)
v. Limit alcohol to  2 drinks/day (men) and  1 drink/day (women)
13. Identify the lifestyle modifications recommended to manage BP; discuss the different class of BP
drugs and how they work
a. DIURETICS
i. Cause kidneys to excrete excess water and Na
ii. Commonly used for uncomplicated HTN
iii. Most commonly used = hydrochlorothiazide (HydroDiuril, Microzide)
iv. Side effects:
1. Increase frequency of urination
2. Increased urinary excretion of potassium (need to consume even more potassium to
counter this effect)
b. ANGIOTENSIN-CONVERTING ENZYME (ACE) INHIBITOR
i. Blocks the action of angiotensin II  decreases BP
1. [review graph on angiotensin II]
ii. Stabilizes plaque deposits
iii. Inhibits blood clotting
iv. EX: benazepril, captopril, enalapril, fosinopril, lisinopril, quinapril, Ramipril, trandolapril
v. SIDE EFFECTS:
1. Some patients develop a chronic nonproductive cough
2. Rarely – sudden swelling of the lips, face, and cheek areas in an allergic reaction
c. BETA BLOCKERS
i. Block the action of catecholamines (epinephrine and norepinephrine)
1. Concentration of epi/NE increases BP
ii. Slows the heart
iii. Causes vasodilation
iv. EX: atenolol, bisoprolol, carvedilol, metoprolol, timolol
v. SIDE EFFECTS
1. Slowing the heart rate excessively
2. Worsening heart failure
3. Rarely – confusion, depression, and impotence
d. CALCIUM CHANNEL BLOCKERS
i. Decrease Ca from entering vascular smooth muscles  decrease contraction of vascular
smooth muscle  increase blood vessel diameter (vasodilation)  decrease BP
ii. EX; diltiazem, vermapil
iii. SIDE EFFECTS:
1. Use with caution in patients with pulmonary arterial hypertension
2. Diltiazem and verapamil worsen congestive heart failure symptoms
3. Verapamil may occasionally cause constipation
4. Headache and edema (swelling) in the ankles and feet