Lec 11

Thyroid Gland Location + Structure

Located just below the larynx and has right and left lateral lobes connected by the isthmus; the ONLY gland that stores its products in large quantities (100 days)

Example of Thyroid Hormone + Function

Thyroxine/Calcitonin, regulates the rate of metabolism and increase osteoblast activity

What hormones are important in calcium homoestasis?

Calcitonin (CT), Parathyroid Hormone (PTH), Calcitriol

Why is Calcitonin important in calcium homeostasis? (Reasons)

LOWERS blood level of calcium and phosphates by:

-inhibiting bone resorption by osteoclasts (bone matrix breakdown)

-increase osteoblast activity (calcium uptake)

-increase calcium excretion in urine by kidneys

-also controls levels of phosphates

Calcitonin Production: what is it produced by & what controls the secretion of calcitonin

Produced by parafollicular (aka "C" = Clear) Cells, the calcium levels in the blood control the secretion of calcitonin

Is Calcitonin essential for the matienance of calcium homeostasis?

NO, calcium levels are still maintained as long as the parathyroid hormone levels are normal

Parathyroid Location + Structure

4 parathyroid glands on the back/posterior thyroid, they consist of principal (chief) cells which secrete parathyroid hormone (PTH) or parathormone

What is the hormone released by the parathyroid gland + its function?

Parathyroid hormone (PTH) or parathormone:

-Regulates the homeostasis of calcium by increasing blood calcium level

-Increases the number and activity of osteoclasts, resulting in increased bone resorption

-Acts on kidneys to increase the rate of removal of calcium from urine, returning it to the blood

-induces formation of calcitriol (synthesized from Vitamin D in the kidneys); in turn, calcitriol will increase the absorption of calcium from the digestive tract into blood

What controls the secretion of PTH?

Calcium levels in the blood

PTH and Calcitonin Relationship

PTH has the OPPOSITE action of calcitonin

What level of blood calcium will trigger the secretion of PTH?

less than 8.7 mg/dl of blood, PTH will increase the normal blood calcium

What level of calcium in the blood will cause calcitonin to be secreted?

Greater than 10.4 mg/dl of blood, the secretion of calcitonin by the thyroid gland will decrease levels to normal blood calcium

Osteitis Fibrosa Cystica

Excess PTH → bone mineral loss → weak, deformed bones.

What is normal calcium levels in the bone?

8.7 - 10.4 mg/dL

Bone is the major reservoir for what?

Calcium, this is closely regulated because of calcium's importance in cardiac, nerve, enzyme, and blood physiology

What is Calcium Deficiency?

Hypocalcemia (less than 8.7 mg/dL), excitability of the NS/tetany

Hypocalcemia Process

Low Ca → Na⁺ channels open more easily → hyperexcitable nerves → tetany.

neurons depolarize. in its most extreme form sustained contraction (tetany) of the respiratory muscles can lead to asphyxiation

Reason for hypoclacemic excitability

low extracelluar ca2+ - fewer calcium ions binding negative surface charges → less charge difference → sodium channels open more easily and open longer → sodium ions enter cell too freely which excites nerve and muscle cells (neurons hyperexcitable)

What is Calcium Excess?

Hypercalcemia, higher than 10.4 mg/dL, depression of the NS/Cardiac Acrres

Hypercalcemia Process, why is it depression of the NS?

Neurons become less permeable to sodium ions, more calcium binds negative charges → greater charge difference → na channels harder to open → reduce na entry → leading to depression of the NS (hypoexcitable)

What is the normal phosphorus levels in the blood?

3.5 - 4.0 mg/dL

Negative Feedback System for the Regulation of Blood Calcium, low → normal

-Hypocalcemia occurs

-Cells in parathyroid gland detect the lowered Ca levels

-increase in synthesis and secretion of parathyroid hormone

-Osteoclasts increase bone resorption and kidneys retain Ca in blood and produce calctriol

-Increase in Blood Ca level and a return to homeostasis

If Calcium Homeostasis is thrown off?

-If levels are too high = Cardiac Arrest

-If levels are too low = Respiration may stop

Calcitonin Function

Secreted by thyroid gland and DECREASES blood Ca levels; produced during hypercalceia

Fracture Repair Process

-Formation of a blood clot called a fracture hematoma (bone cells in this site die), this is organized into granulation tissue called a procallus (actively growing connective tissue)

-Transformation via fibroblasts and osteogenic cells into a fibrocartilaginous - soft callus (callus = mass of repair tissue that bridges the broken ends of bones)

-Conversion of fibrocartilaginous callus into spongy bone (hard callus) via osteoblasts

-Remodeling of callus to nearly original form

If fracture damage is extensive, what can be done?

Exogenous (artifical) stimulation of bone repair, 2 types: Surgical Bone Grafting and Pulsating Electromagnetic Fields

Surgical Bone Grafting

Dead bone, bone fragments, living bone from another side/cadavers can be inserted within the fracture to provide a bony model for the repair process

Pulsating Electromagnetic Fields

When a bone is stressed, the mineral crystals in them generate small electrical fields, and osteoblasts are attracted to these electrical fields and start producing bone materials; pulsating, low frequency electromagnetic fields are generated in a therapy mattress to trigger osteoblasts

Who most commonly uses Pulsating Electromagnetic Fields?

Commonly used on profession athletes/collegiate athletes/fractures in elderly patients

Success rate of Pulsating Electromagnetic Fields?

80%+

Closed Fractures

Internal, the bone does not protrude through the skin (simple)

Open Fractures (Compound)

Bone protrudes thru skin, MOST DANGEROUS due to infection bc they have contacted the environment

Open Fractures commonly found in + risk for?

Most commonly seen in car/motorcycle accidents and are at high risk for infection or osteomyelitis

Comminuted

Fracture that is broken into more than 1 fragment

Greenstick

Fracture where one side is broken and the other is bent, due to the pliability of pediatric bones (Not a complete fracture)

Greenstick Fracture: Which side is broken, which is bent?

Medial side of radius is open, lateral cortex has simply buckled

Spiral

Fracture where the bone is twisted apart, wavy appearance due to torque thru bone

Spiral Fractures can be most commonly seen in?

Children when they twist an ankle or knee, can alert providers since if this occurs in a child who has no yet started walking it could be a result of child abuse

Stress Fractures

Common result of overuse/stress on bone, better to catch them before they become complete fractures because they are non-displaced and tend to heal well with appropriate treatment

Transverse

Fracture where a break of a bone shaft is across its long axis

Displaced

Fracture which produces new arrangements of ony elements

Displacement

The change in anatomic axis of on fragment with respect to another, amount of displacement is measured as shaft width/percentage

Example if a Displacement Measurement

Femur displaced at 1/2 shaft width = 50% full shaft width

Nondisplaced

Fracture that retains the normal alignments

Pott's

Fracture of the distal end of the lateral leg bone (fibula) with serious injury of the distal tibia articulation

Colles'

Fracture of the distal end of the radius in which the distal fragment is displaced posteriorly

Pathological

Weakening of the bone caused by a disease process: osteosarcoma (cancer), osteomyelitis (inflammation), osteoporosis (decreased bone mass)

Aging's affect on Bone Tissue

Mostly due to loss of calcium and other minerals from bone matrix (demineralization)

Osteopenia

A milder condition of bone tissue loss, we all suffer from it as we age

Osteoporosis

A more extreme condition of bone tissue loss; impaired proper functioning of bone and occurs mostly in biological females after age 30 as estrogen levels decrease

How much has the U.S. paid to treat osteoporosis and its associated bone fractions?

Over 6 billion every year

Osteoporosis Bone Fractures

Can lead to considerable disability and in many cases premature death

What hormone regulates the bone deposition process? (It's more present in biological females)

Estrogen

Who has more estrogen after menopause?

Biological men

Aromatase

An enzyme which can convert testosterone into estrogen, aromatase is present in the male genital tract

Where is testosterone produced in biological males?

Testis (95%) and Peripherally (Adrenal Gland)

Osteoporosis Detection

DXA (Dual-energy X-Ray absorptiometry) X-ray scan measuring bone density (spine, hip, wrist).

What are the most common sites for osteoporotic fractures?

Spine, Hip, Wrist

DXA Specifics

x-ray exposure is 1/10th of a standard chest x-ray; Two X-ray beams with different energy levels are aimed at the patient's bones

Causes of Osteoporosis

-Lack of estrogen after menopause

-Prolonged treatment with large doses of glucocorticoids

-Immobilization

-Weightless Conditions of Space Travel

-Other factors: Lean builds, smokers, excessive consumption of alcohol, caffeine (these factors are not well understood)

Estrogen

Seems to stimulate the production of osteoblasts

Glucocorticoids

Might be used for immunosuppressives or asthmatic therapy; they antagonize the actions of Vitamin D (causes Vitamin D Deficiency) which leads to calcium deficiency

How do glucocorticoids act?

Act locally within bone cells and modulate their proliferation, differentiation, and cell death

What does caffeine seem to do?

Decrease calcium absorption

What is the gold standard of treatment for osteoporosis and why?

Hormone replacement therapy (HRT), because it has proved to be the best protection against bone loss

Hormone Replacement Therapy

Combination of estrogen + progesteron helps overcome the side effects of treatment with high estrogen levels

If HRT only had estrogen what would happen?

Increase in breast and endometrium cancer

Benefits of Estrogen

Besides osteoporosis treatment, reduces a biological woman's risk of cardiovascular disease and unwanted side effects of menopause, such as hot flashes

Caution about HRT

Daily use of combined HRT (Estrogen and Progesterone) increased a biological woman's chance of developing breast cancer by about 25% after she took it for several years + more likely to have abnormal results on mammograms

What is the daily intake of Calcium in the U.S.?

450 - 550 mg

What is the National Research Council's reccommended dietary intake of calcium per day?

800 mg

How much calcium should be taken per day for pre-menopausal and estrogen-treated biological females and biological males?

1,000 mg

Reccommended daily calcium intake for post-menopausal biological females who are not treated with HRT

1,200 mg

What are some other drugs/treatments that can protect against bone loss, WITHOUT estrogen side effects?

Bisphosphonates, EVISTA/Raloxifene (SERM), Calcitonin, in the future parathyroid hormones, exercise, and rosy future

Bisphosphonates

Do NOT bind to estrogen receptors and enter the cell directly; Inhibit osteoclasts → ↓ bone resorption; inhibit FPPS enzymes

EVISTA/Raloxifene

Acts like estrogen in bone; blocks estrogen in breast tissue.

activation of the estrogen receptor can spur breast cancer growth; so EVISTA, by blocking the estrogen receptor on the breast tissue, might actually reduce the risk of breast cancer

Calcitonin

Normally produced by thyroid gland to help body maintain calcium homeostasis, can be given as a subcutaneous injection or as a nasal spray because it is a PROTEIN and would be broken down in the stomach if taken orally

Future Other Treatments of Osteoporosis

Parathyroid Hormones, may be used as an agent to repair the skeleton

Rosy Future

We have diagnostic tools, we have some treatment options, and better treatments are under development; the disease ought to DISAPPEAR in the NEXT CENTURY

Osteogenesis Imperfecta (OI)

Inherited/genetic disease of type 1 collagen (protein "scaffolding" of bone and CT), osteoblast function is impaired (bones are fragile and have too much cartilage), ligaments become very loose

% of children who have OI with no family history of it

25%, sometimes this can cause OI to be mistaken for child abuse

Marfan Syndrome

Too much cartilage at the epiphyseal plate which leads to extremely long and slender limbs; caused by defective fibrillin gene leading to abnormal elastic fibers

Pituitary Gland

Small pea sized gland located at the base of the brain, the "master gland" because it receives messages from hypothalamus and tells other glands what to produce; Pituitary gland produces hGH (Human Growth Hormone) which controls HEIGHT

Dwarfism

Pituitary gland secretes LESS hGH than normal, person is typically shorter than normal but has normal body proportions, mental capacity, and sexual development (avg height is less than 50 inch); treated with hGH

Gigantism

Anterior lobe of pituitary gland secretes TOO MUCH hGH, this is caused by late ossification/hardening of the bones; metabolic rate increases up to 20% above normal rate which causes HYPERGLYCEMIA and eventually DIABETES; treated with IRRADIATION. this is before epiphyseal closure / during childhood

Acromegaly

Caused by oversecretion of hGH but unlike Gigantism has an overgrowth of hands, feet, and lower part of face; occurs after puberty when most of the epiphyseal cartilage have closed but the cartilages and small bones still respond to hGH; consequences = physical overgrowth, weakness and diabetes mellitus (pancreas secretes too much or too little insulin); treatment = surgical removal of hyperfunctioning tissue, irradiation, and drugs to supress growth hormone

Paget's Disease

Characterized by MASSIVE OSTEOCLASTIC RESORPTION AND EXTENSIVE BONE FORMATION,

interferes with your body's normal bone remodeling process which is vital to maintain calcium homeostasis,

this disease most commonly occurs in the pelvis, skull, spine, and legs

can also undergo sacomatous degeneration (other cancers such as prostate cancer) and can metastasize to bone involved with Paget's disease

Rickets in Children and Osteomalacia in Adults

Bone becomes too flexible due to LOSS OF CALCIUM and VITAMIN D DEFICIENCY; results in inadequate mineralization of the bone

Osteogenic Sarcome

Bone cancer that primarily affects the osteoblasts

Osteomyelitis

Inflammation of a bone and marrow caused by a pathogenic organism

Cleft Lip and Cleft Palate

Result from a lack of fusion of portions of the maxillary and palatine bones during fetal development,

early treatment of surgical repair, speech therapy, and orthodontia can result in normal speech and few (if any) lasting effects

Sinusitis

Membranes of the paranasal sinuses become inflamed due to infection or allergy, blockage of the outlets into nasal cavity ca cause painful building of pressure in sinuses

Temporomandibular Joint Syndrome

LOCK JAW: dysfunction to varying degrees of the temporomandibular joint,

causes: improperly aligned teeth, grinding or clenching teeth, trauma to the jaw, arthritis

Abnormal curves of the spine

Resulting from an exaggeration of normal curves in the vertebral column, 3 types: Scoliosis, Kyphosis, Lordosis

Scoliosis

Lateral curvature, usually in thoracic region

Kyphosis

Exaggerated Thoracic Curve

Lordosis

Exaggerated Lumbar Curve

Spina Bifida

Congenital defect from failure of vertebral laminae to unite at the middle (can involve one or many vertebrae and nervous tissue may or may not protrude through bone), interferes with normal nerve function below the point of defect

Spina Bifida Detection and Treatment

Spina bifida can be diagnosed prenatally by elevated alpha-fetoprotein (AFP) levels, produced by the fetal liver. Treatment may include C-section delivery, surgical repair at birth, or fetal surgery. It is associated with folic acid (vitamin B9) deficiency.

Flatfoot and clubfoot

Caused by decline or elevation of the medial longitudinal arches, also produced by muscular abnormalities; the feet are turned MEDIALLY and INVERTED