Mineral Homeostasis Flashcards
- __% of the Calcium in our bodies is found in our ____
- ____% of total adult bone mass turnover occurs annually due to bone ______
- During growth the rate of bone ______ exceeds _____ leading to the skeletal mass to ________
- _______ growth occurs at the _____ plates
- Increase in bone width occurs at the ______
- Rate of _______ & ______ are equal until ~30 where the rate of ________ begins to exceed the rate of _______ and bone mass _______
- 99%; bones
- 10%; remodeling
- Formation; resorption; increase
- Linear; epiphyseal
- Periosteum
- Formation; degradation; degradation; formation; decreases
- 20% of adult bone is _____/_____ bone
- 80% of adult bone _____/_____ bone. Is ___, ____, and solid bone that forms the _____: the outer shell of most bones. Provides _____ and ______ to the bone
- Trabecular; Spongy
- Cortical; Compact
- Dense; stiff;
- Cortex; strength; protection
-Active _______ synthesize and extrude
collagen
-Collagen fibrils form arrays of an organic matrix
called the ____
-______ ______ is deposited in the osteoid and
becomes mineralized
-Dependent on _______
-______ ______ and ______ play roles in
bone formation and their plasma levels are indicators of _____ activity
- Osteoblasts
- Osteoid
- Calcium Phosphate
- Vitamin D
- Alkaline Phosphatases; Osteocalcin; Osteoblast
-Interior ________ remain connected to surface
cells via transfer of ________ from enormous
surface area of the interior to extracellular fluid.
-Osteocytes; Calcium
Bone Resorption of Calcium by 2 Mechanisms:
1) ______ _____: Is a rapid and transient effect
2) _____ ______: Is slow and sustained
-Bone formation and resorption are mainly
regulated by _____ ____(___) and
Vitamin ____.
1) Osteocytic Osteolysis
2) Osteoclasitic resorption
- Parathyroid Hormone (PTH); VitaminD
Osteocytic Osteolysis -Transfer of \_\_\_\_\_\_\_\_ from canaliculi to extracellular fluid via activity of \_\_\_\_\_\_, by removing \_\_\_\_\_\_\_ from most recently formed crystals -\_\_\_\_\_\_ decrease in bone mass -Very \_\_\_\_\_\_ process
- Calcium; Osteocytes; Calcium
- NO
- Fast
Osteoclastic Resorption
-Does not merely extract ______, it _______
entire matrix of bone and ________ bone mass
-Cell responsible for resorption is the ________
- Calcium; destroys; diminishes
- Osteoclast
Mineral Homeostasis
-______ and ________ ions can combine to form
insoluble ______, the concentrations of these ions in
cells and body fluids is precisely regulated to
prevent inappropriate _______
-Mineral balance is achieved by ______ control
of ______ & ______ transport into and out of ______, ______, & _____
- Calcium and phosphate; salts; precipitations
- Hormonal; Calcium & Phosphate; Intestines; Kidneys; Bone
Importance of Calcium
-In bone provides structural ________ of the skeleton
-Most abundant ______ in the body
-Amount of Calcium is balanced among ______, ____, and _______, which is controlled via Calcium transfer from the 3 organs
Calcium in Extracellular and Cellular Fluids:
-__________ excitability and signal ______
-Blood ______
-________ secretion
-________ regulation
-________ excitation
- Integrity
- Mineral
- Intestines, kidney, bone
- Neurmuscular; transduction
- Coagulation
- Hormonal
- Enzymatic
- Neuron
Calcium in the Body
-~______ of Ca is ingested per day, and absorption occurs in the ____ _______, and
requires ________
-An adult human contains ~ _________g of Calcium
-Extracellular [Calcium] is ~_____ mg/dL, and [Calcium] in the cytosol is ~ ______M
- 1000mg; small intestines; Vitamin D
- 1,000g
- ~10mg/dL
- ~10-7 M
Regulation of Intracellular Calcium
- Stored in the ______ and ____
- ______ transport systems control intracellular [Calcium], where it gets pumped into storage site in _______ to avoid forming _______ pools
- Mitochondria; ER
- “Pump-leak”; organelles; cytosolic
Extracellular Calcium
- Normally ranges from _____ mg/dL in the
_____
3 forms of Calcium in serum:
1) _______ calcium makes up ____% of the total and is biologically ______
2) _______ calcium makes up ___%, where 90% is bound to _____ and the rest is bound to globulins
3) Calcium complexed to serum ________ (_____ & phosphate) make up 10%
- 8.5-10 mg/dL; blood
1) Ionized; 50%
2) Protein-bound; 40%; albumin
3) Constituents; Citrate
Daily Calcium Turnover
- Intake of ~____mg of ____ Calcium
- ~___mg of unabsorbed dietary Calcium and ~____mg of fecal Calcium are excreted
- The _____ filters ~______ mg/day and ~200mg get excreted in the _____, 98% of the _____ Calcium is exchanged back into the _____
- ~350mg gets absorbed into the ____ from the intestine, ~_____ mg goes back into the intestines, and bone _____ results in ~____mg being absorbed back into and from the bone with the _____.
- Bone contains ~______ mg of Calcium
- 1,000mg; dietary
- 650mg; 150mg
- Kidney; 10,000 mg/day; urine; filtered; blood
- blood; 150mg; remodeling; 500mg; blood
- 1 million mg
- ~_____ mg of phosphate is ingested per day
-Phosphate is absorbed in the _____ ____,
stored in the ______ and excreted by the ______
- 1,000
- Small Intestines; Skeleton; Kidneys
Storage of Phosphate
-An adult human contains approximately _____g of
phosphorus
-~ ____% of this is present in crystalline form in the
______
- ~___% is present in the _________ fluids, and the concentration in cells is ~___mM
-Phosphate concentrations are ____ rigidly maintained than that of ______
- 700mg
- 85%; skeleton
- 15%; extracellular; 5mM
- Less; Calcium
Phosphorous in Blood and Bone
-PO4 normal plasma concentration is _____ mg/dL.
87% is ______, with 35% complexed to
different ____ and 52% ionized.
-13% is in a non-diffusible _____ ____ state. 85-90% is found in ___
- The rest is in ____, ____, & ______
- 3.0-4.5 mg/dL; diffusable; ions
- protein bound; bone
- ATP; cAMP; & proteins
Regulation of Pi homeostasis
- Cells require adequate Pi for ____ metabolism and ____ ___ synthesis
- Cells take up Pi from the ____ using _______, a form of active transport
- Absorption and reabsorption of Pi occurs primarily in the ______ and the _____
- Pi is regulated by ____, _____, and _____
- Energy; nucleic acid
- blood; Na+/Pi co-transporters
- Intestines; kidneys
- PTH; Vitamin D; FGF23
Hormonal Control of Calcium
Major Hormones:
-__________: Acts on the intestines, kidneys, and bones
-______ ______(___): Acts on the kidneys and bones
-__________: Acts on the kidneys and bones
-Both ______ & _____ increase blood calcium, while _____ decreases it
- 1,25(OH)2 Vitamin D3
- Parathyroid Hormone (PTH)
- Calcitonin
- Vitamin D & PTH; Calcitonin
Vitamin D
-Is the precursor of the hormone __________, which increases absorption in the ______ and reabsorption in the _______
2 Natural Forms of Vitamin D:
1)______/______: Derived from the plant steroid ergosterol
2)______/______: Derived from cholesterol
-Both must be _______ to be in the active form, this occurs in the ______, and the rate is determined by ____
-Dietary Vitamin D is usually ____
- 1,25 (OH)2 Vitamin D3; small intestine; kidney
- Vitamin D2/Ergocalciferol
- Vitamin D3/Cholecalciferol
- Hydroxylated; kidney; PTH
- Vitamin D2
Health Problems Associated with Vitamin D Deficiency
Causes:
-Lack of ____ exposure
-__________ & supplements
-_________ related diseases like Crohn’s, Whipple’s, Cystic fibrosis, Coeliac, or liver disease
-______ & _______ failure
-_________
Consequences:
-Mental problems like ________ & _______
-Higher rate of _______
-______ disease
-__________ diseases like Type 1 diabetes & Rheumatoid arthritis
-Many different ________
-Bone diseases: ______, ________, & _______ (children only)
Causes: -Sun -Medications -Malabsortption -Renal & hepatic -Obesity Consequences: -Schizophrenia & depression -Autoimmune -Cancers -Osteoporosis; Osteomalacia; Ricketts
Mechanism of Vitamin D Action
-______ _______(___): Belongs to the steroid/thyroid hormone receptor superfamily. Binds cooperatively to ____ ____ ____(___) as a heterodimer with the Retinoid X Receptor (RXR)
-Vitamin D Receptor (VDR); Vitamin D response elements (VDREs)
- Calcium is dependent on ___________ for absorption by inducing the production of _____ _____ _____ that sequesters Calcium allowing it to be absorbed ______ the gradient
- In the small intestines is greatest in the _____>____>____
- _______ is better at low pH, with peak absorption at the beginning of the ______
- Vitamin D; Calcium Binding Proteins; Against
- Duodenum; Jejunum; Ileum
- Absorption; duodenum
Vitamin D Actions on Bones
- _______ have Vitamin D receptors and ______ do not
- Absence of _____ results in excess ______ accumulation, repressing Osteoblastic _____ synthesis
- ________ stimulates Osteoblast to produce a ______ signal to activate ______ to resorb Calcium from the matrix
- ________ also stimulates the process _______ _______
- Osteoblasts; Osteoclasts
- 1,25 (OH)2 Vitamin D3; Osteoid; Collagen
- 1,25 (OH)2 Vitamin D3; paracrine; Osteoclasts
- 1,25 (OH)2 Vitamin D3; Osteocytic Osteolysis
Regulation of Vitamin D
- _____ increases 1-hydroxylase activity, increasing production of active form. This ______ absorption in the intestines; _____ release from the bone; and _______ loss in the kidneys
- ____ is regulated via negative feedback inhibition
- Low [_____] increases 1-hydroxylase activity increasing production of the active form and ________ reabsorption from the urine
- PTH; increases; increases; decreases
- PTH
- [Phosphate], phosphate
Vitamin D Deficiency caused Skeletal Diseases
- ______ _____ ______: In children, where a softening of bones potentially leading to fractures and deformity, due to defective _______ or _______ of bones
- ________: Adult form of Rickets
- _______ _____: Mutation in the Vitamin D Receptor
- _________ _____: Hereditary disease of phosphate metabolism (PHEX mutation)
- ________ ______: Genetic defects in Vitamin D metabolism (CYP27B1 loss of function)
- Vitamin D-dependent Rickets Type II; mineralization; calcification
- Osteomalacia
- Vitamin D-resistant Rickets
- Hypophosphatemic Rickets
- Pseudo-deficiency Rickets
PTH
- An 84 amino acid _______ polypeptide hormone, where only the first _____ amino acids are essential for ______
- Synthesized and secreted by the _______ ______ (just posterior to the ____ ____, and receives its blood from the ____ _____), primarily synthesized by _____ _____
- Major player in Calcium _________ in humans
- Monomeric; 34; function
- Parathyroid gland; thyroid gland; thyroid arteries; Chief Cells
- Homeostasis
Actions of PTH
-In the blood it ______ [Ca] and _______ [Pi]
-Acts directly on ____ to simulate the slow ______ and _____ of Calcium into the extracellular space. _____ in Osteoblasts increases [cAMP] to activate PKA that _____ function when PTH is secreted continuously
2 Effects in Kidneys:
1) Acts directly on kidneys to _____ increase calcium ______ and phosphate ______ by acting on the distal tubule. Inhibited by _________, another hormone.
2) Stimulates transcription of ________ for Vitamin D activation, this _______ both calcium and phosphate absorption
- Increases; decreases
- Bone; resorption; release; GPCRs; inhibits
1) Quickly; reabsorption; excretion; Calcitonin
2) 1-hydroxylase; increases
Parathyroid Hormone Receptor PTH1R
-Highly expressed in the _____ and ______, as well as in growth plate _______ by mediating paracrine/autocrine actions of _______ when in tissue other than the ______ and ______
-Kidney; bone; chondrocytes; PTHrP; kidneys; bone
- PTH can have both catabolic and ______ effects on bone depending on the ________ of its application
- ___________ administration of PTH can be useful in treating ____________ & __________ disease
- Anabolic; kinetics
- Intermittent; Osteoporosis; Periodontal
PTH Regulation
- Regulated by plasma [____] via an ______ relationship
- Maximum secretion with plasma [_____] below 3.5 mg/dL, this is below the average amount indicating the body needs more [_____]
- Plasma [____] above 5.5mg/dL _____ PTH secretion, this is above the average amount indicating the body needs less [_____]
- [Calcium]; inverse
- [Calcium]; [Calcium]
- [Calcium]; inhibits; [Calcium]
-_____: Cell surface GPCR capable of detecting small changes in serum [Calcium], that is expressed in the _____ _____, ______, and _______
-CaSR; Kidney tubules; Chondrocytes; Osteoblasts
- _______: 32 amino acid long product of Parafollicular/C Cells in the Thyroid that inhibits Osteoclast bone _____ and promotes renal ______ of Calcium
- Secreted to a rise in plasma [______] that targets ______ by increasing [cAMP] to inhibit their motility and cell shape which _______ them. Results in a ______ fall of [Calcium] by halting bone _______
- Calcitonin; resorption; excretion
- [Calcium]; Osteoclasts; inhibits; rapid; resorption
Growth Hormones
- Normal levels are need for _______ growth
- _______ intestinal Calcium absorption and renal phosphate resorption
- Low levels prevent normal bone _______, while excessive levels result in bone _________
- Skeletal
- Increased
- Production; abnormalities
Glucocorticoids (__________)
- Normal levels are necessary for ______ growth
- _________ levels decrease renal calcium reabsorption, interfere with intestinal calcium ________, and stimulate ____ secretion. Additionally interfere with ______ _____ production and action; and Gonadal Steroid production
- Too high levels cause rapid ______
- Cortisol
- Skeletal
- Excessive; absorption; PTH; Growth Hormone
- Osteoporosis
Thyroid Hormones
- Important for skeletal growth during ______ and _______ by directly effecting Osteoblasts
- ________ leads to decreased bone growth
- ________ can lead to increased bone ____, suppression of ____, decreased _______ metabolism, and decreased Calcium _______; all lead to _______
- Infancy; childhood
- Hypothyroidism
- Hyperthyroidism; loss; PTH; Vitamin D; absorption; Osteoporosis
Effects of Diets
- ________: Essential minerals that cannot be made and must be ingested
- Increasing dietary intake of _______ may prevent ______ in postmenopausal women
- Excessive _____ intake can impair renal Calcium reabsorption, _____ blood Calcium thus increasing ___ synthesis & release. Due to a decreased ______ production in aging women, Calcium does NOT get absorbed so PTH causes increase bone ______.
- High ______ diet can cause Calcium bone loss due to the resulting ______ environment
- ________ beverages is associated with increased ______ and loss of Calcium
- Biominerals
- Calcium; Osteoporosis
- Sodium; decreasing; PTH; Vitamin D; loss
- Protein; acidic
- Carbonated; excretion
Effects of Exercise
-Bone cells respond to ______ gradients in
laying down bone
-Lack of weight-bearing exercise _______ bone formation, while _______ exercise helps form bone
-Increased bone resorption during _______ may result in hypercalcemia
- Pressure
- Decreases; increased
- Immobilization
Osteoporosis
-Osteoporosis is characterized by a significant _______ in bone mineral _____ compared with age- and sex matched norms
- Decrease in both bone _____ and bone ____
-Most common ______ bone disease
-Women lose 50% of their ________ bone and 30% of their ______ bone
-30% of all ___________ women will sustain an
osteoporotic fracture as will ____ of all men
- Reduction; density
- Mineral; matrix
- Metabolic
- Trabecular; Compact
- Post-menopausal; 1/6th
Vitamin D Deficiency: Rickets
-Inadequate intake and absence of _______
-The most prominent clinical effect of Vitamin
D deficiency is _______, defective mineralization of the bone matrix
-Vitamin D deficiency in children produces _______
-Deficiency in the _________ enzyme produces Vitamin D-resistant Rickets. This is a ___ _____ gene on the X chromosome, resulting in renal tubular defects of phosphate _____.
Phenotypes:
-Teeth can be ______ (thinning) or the __________ (decreased mineralization) of enamel
-Delayed ______ of teeth
-Minimal caries can result in _______, resulting in ______ abscesses being common
-Sunlight
-Osteomalacia
-Rickets
-1-hydroxylase; sex linked; reabsorption
Phenotypes:
-Hypoplastic; Hypocalcification
-Eruption
-Pulpitits; Periapical
