Endocrine + Bone Flashcards
What are the functions of the thyroid gland?
- secrete thyroid hormone from follicle cells (metabolism)
- secrete calcitonin from parafollicular cells (regulate circulating Ca2+)
Is the thyroid gland highly vascularized or barely vascularized?
highly!
How are thyroid hormones produced?
- iodine from diet attaches to tyrosine to form MIT or DIT
- T3 = MIT + DIT
- T4 = DIT + DIT
Is more T3 or T4 produced in the thyroid gland? Why?
- more T4 is made
- only small amount of free hormone –> pituitary respond to and regulates free hormone
What form is of thyroid hormone is T3? T4?
T3 = active form
T4 = storage form (can be converted to T3)
both are mainly bound to plasma proteins (TBG - thyroxin binding globulin)
What is TRH (thyrotropin releasing hormone)?
- regulates thyroid via endocrine feedback loop
- released from hypothalamus –> blood –> pituitary
- increased activity of transporters –> increases iodine –> increased production of T3/T4 (determined by TSH release)
What is hyperthyroidism?
- body wasting, nervousness, tachy, tremor, ++ heat production, high BMR, affects reflexes and brain development
- TSH is low
What is hypothyroidism?
- fetal/neonatal: mental retardation, dwarfism, short limbs (tx at birth has good prognosis)
- adult: mental + physical slowing, poor resistance to cold myxedema, low BMR
- TSH is high
What is the relationship between TSH and thyroid hormone?
- decreased free TH (increased binding hormones) –> increases production of TSH –> increases TH production until levels return to normal
What are deiodinase isozymes?
- cause deiodination (require selenium)
- D1 converts T4 to T3 in the liver, kidney, and thyroid (most important)
- D2 converts T4 to T3 in the brain, pituitary, brown fat, heart, skeletal muscle
- D3 converts T4 to rT3 in the placenta, skin, brain
What cellular affect does thyroid hormone have?
- T3/T4 enters nucleus
- Binds to TH-receptor
- CoActivators are recruited to T3-bound TH-R
- Gene expression is altered (silenced)
Why is T3 the favorite child?
- 4x more biologically potent than that weakling T4
- 10x greater affinity for receptors than T4
What causes hypothyroidism?
- primary (problem w/thyroid): thyroid ds, lack of thyroid, Hasimotos (autoimmune destruction)
- secondary (problem w/TSH): anterior pituitary d/o, hypothalamus d/o
- iodine deficiency (decreases TH, increases TSH –> gland hypertrophies –> goiter)
What causes hyperthyroidism?
- Graves’ (most common): antibodies stimulate TSH receptor –> excess T3/T4 –> goiter
- Solitary adenoma (lg amts of TH)
- Hashimotos in early stages (increased TH secretion)
- TSH-secreting pituitary tumor
- mutations causing activation of TSH receptor
- administration of T3/T4
What other parts of the body does thyroid hormone affect?
- adipose tissue (stims lipolysis)
- heart (chrono/inotropic)
- muscle (inc protein breakdown)
- bone (+ growth + skel dvlpt)
- NS (+ brain dvlpt)
- gut (inc carb absoprtion)
- metabolic (inc met rate, stim O2 consumption by metabolically active tissues)
How does bone growth occur?
- new bone forms at end of shaft to increase length
- exceptions: mesenchymal cells form bone directly in clavicles, mandibles, certain skull bones
- growth stops when epiphyses unit w/shaft + form epiphysial closure (cartilage cells stop proliferating)
How is bone balanced?
- bone growth ends at puberty but bone is still dynamic (10y turnover)
- in a healthy person, resorption = formation
- -> PTH inc remodeling, estrogen dec resoption
What is PTH?
- parathyroid hormone
- increases Ca2+ resorption, decreases phosphate reabsorption
What is PTHrP?
- parathyroid related protein
- binds to same receptor as PTH - acts as a paracrine factor
- proper eruption of teeth
What is the role of Vitamin D on Ca2+?
- inc retention in kidney
- inc uptake in gut
- stims osteoblast production in bone –> stims osteoclasts –> Ca2+ resorption
What is calcitonin?
decreases Ca2+ retention (opposes osteoclasts –> dec plasma Ca2+) by inhibiting absorption in gut, inhib osteoclasts + stimulating osteoblasts, + inhibiting renal tubule reabsorption (excrete Ca2+)
How does estrogen affect bones?
- normally inhibits osteoclast development indirectly (inhibs IL-1, IL-6, TNFa)
- after menopause –> deficiency causes bone loss
Where is calcium found?
- mainly in bone (stable)
- small amount exchangeable
- binding is proportional to plasma level
What causes hypercalcemia?
- hyperparathyroidism, cancer
- leads to anorexia, NV, depression, coma, constipation
What causes hypocalcemia?
- hypoparathyroidism, VitD deficiency, kidney ds, malabsorption
What happens when plasma Ca2+ is low?
- Inc PTH secretion –> inc plasma PTH
2a. Kidneys increases Ca2+ reabsorption (decrease urinary excretion) + increase vitD (–> intestines increase Ca2+ absorption)
2b. Bone increases resorption (–> increased Ca2+ release into plasma) - Restoration of plasma Ca2+ to normal
What is osteoporosis?
- abnormal loss of bone (remaining bone is intact)
- excess osteoclast activity
- -> fractures, widow’s hump
What is osteopetrosis?
- abnormal hardening of bone
- d/t defective osteoclasts (unopposed actions of osteoblasts)
- hematologic abnormalities
- -> dense, thick bones
What is osteomalacia?
- abn bone frmn d/t inadequate mineralization in adults + growth plates closed (Rickets) in kids > vit D deficiency
- -> weakness of wt-brg bones, dental defects, hypoclacelmia, bow-legged
What is Paget’s Disease?
- abn bone remodeling d/t uncontrolled/abn osteoclast
- -> deformity, fractures
What are the functions of the endocrine system?
- energy balance
- metabolic rate (storage + brkdn of metabolites)
- homeostasis (blood vol, osmolarity, glc, electrolytes)
- reproduction
- G&D
- environmental adaptation (temp, stress)
What are the two types of hormones in the endocrine system?
- proteins (AA derivatives): ACTH, insulin, GH, glucagon, LH, FSH, TSH, HCG, T3, T4, epi
- steroids (cholesterol derivatives): glucocorticoids, androgens, estrogens
What does the anterior pituitary do?
Secretes:
- ACTH
- LH
- FSH
- estrogen + progesterone
- testosterone
- tSH
- prolactin
- GH
What is panhyperpituitarism?
excess of all anterior pituitary hormones:
- amenorrhea (prolactin)
- hyperthyroidism (TSH)
- gigantism (GH)
- infertility (LH + FSH)
What is panhypopituitarism?
deficiency of all anterior pituitary hormones:
- no lactation (prolactin)
- dwarfism (GH)
- hypothyroidism (TSH)
What does the Posterior Pituitary do?
- paraventricular + supraoptic nuclei: vasopressin/ADH, oxytocin (pregnancy, lactation)
What’s the deal with growth hormone (GH)?
- produced in anterior pituitary
- trophic hormone (stimulates liver to release IGF-1)
- highest lvls during sleep
- release is pulsatile
- stimulated by low blood glc, arginine, catecholamines, CHRH
- Inhibited by glc, IGF-1
What are some causes of dwarfism?
- GH insensitivity
- pygmies (normal GH but can’t produce IGF-1)
- GH deficiency (hypopituitary dwarfism)
What happens in GH excess?
(usually d/t GH-secreting adenoma)
- gigantism (adenoma before puberty)
- acromegaly (adenoma after puberty –> over stimulated bone of soft tissues)
What type of cells are found in the endocrine pancreas?
- alpha cella (secrete glucagon)
- beta cells (secrete insulin, GABA, PTHrP)
- delta cells (secrete somatostatin)
- F type cells (secrete pancreatic polypeptide - PP)
What is the purpose of insulin?
- fuel storage
- decreases blood sugar
How is insulin released?
pancreatic beta cell have glc sensors –> release insulin when glc is high:
- Glc is transported into cell via GLUT1 transporter
- Glc metabolized into brkdn products + ATP
- ATP causes closure of K channels –> cell deps
- Dep causes opening of Ca channels –> ca influx into cell
- Ca influx causes insulin vesicles to fuse to membrane + exocytose
- Insulin travels to liver, muscle/fat (via systemic circulation)
What stimulates insulin release?
- nutrients (oral glc)
- hormones (incretins, glucagon, secretin)
- parasym stimulation (Epi B2 receptors)
What inhibits insulin?
- insulin (negative feedback)
- sympathetic (NE, Epi a2 receptors)
What effect does insulin have on receptors?
(autophosphorylation)
- (acute) translocation of GLUT4 transporter to cm –> insulin enter cell –> glc moves into cell –> dec in plasma glc
- (longer) enzyme phosphorylation cascades: activation/inhibition of metabolism, activation of lipid signaling, altered gene expression (gene transcriptase + prot synthesis)
What does insulin inhibit in cellular glucose pathways?
- glycogenolysis (breakdown of glycogen into glc)
- gluconeogenesis (formation of new glc)
- -> no more glc
What does insulin stimulate in cellular glucose pathways?
- glycogenesis (storage of glc as glycogen)
- glycolysis (breakdown of glc)
- glucose uptake
- -> less glc, more glycogen
What are normal fasting glc levels?
3.5-5.5 mM/L
70-99 mg/dL
What are DM glc fasting levels?
> 7mM/L
>126mg/dL
What’s bad about hypoglycemia?
pathological –> sympathetic CNS sx (confusion, HA, lethargy, seizures, coma)
What’s bag about hyperglycemia?
- pathological –> polydipsia, polyurea, dehydration, fatigue, blured vision, nausea, dKA, Kussmail hyperventilation, arrhythmia, stupor, coma
- chronic: poor healing, atherosclerosis, blindness, kidney failure, amputations, heart disease
What is Type I DM?
- congenital: absent/impaired insulin secretion
- onset <20yo
- caused by beta cell antibodies
- tx: intensive insulin tx
What is Type II DM?
- acquired (obesity): progressively impaired insulin secretion
- onset usually >30yo
- caused by insulin resistance that progresses to beta cell failure
- tx w/diet/exercise, oral/injected agents, insulin
What occurs in insulin resistance?
decreased insulin receptors
increased blood glc levels
What occurs in a lack of insulin?
increased blood glc, fa (ketoacids), and aa levels
acid/base imbalance
HoTN
What stimulates glucagon production?
- hypoglycemia
glucagon fcns to increase blood glc
What inhibits glucagon production?
- increased glc
- insulin
What does glucagon do?
- increases glc, FA, ketoacids
- increases glycogenolysis
- increases gluconeogenesis
What modulates appetite?
- increases: ghrelin, opiods
- decreases: leptin, insulin, glucagon, histamine, serotonin
