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Physiology II > Parathyroid and Vitamin D > Flashcards

Parathyroid and Vitamin D Flashcards

1
Q

Organic Bone Matrix

A

30% of compact bone; more in new bone
90-95% collagen fiber along line of tensile force
5-10% ground substance: ECF and protoeglycan: Chondroitin and hyaluronic acid
controls salt deposition (surround collagen fiber)

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2
Q

Bone Salt Deposits

A

70% of compact bone; less in new bone
Ca and Ph deposited in matrix form hydroxyapatite
Also mg, na, k, carbonate
Heavy metals and radioactive productscan accumulate in bone salt and lead to cancer

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3
Q

Hydroxyapatite crystals

A

Are in conjunction with collagen fibers
Prevents shear and improves bone strength

Precipitate of Ca and P in the bone

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4
Q

Although hydroxyapatite crystals are present in ECF tehy do not precipitate despite supersaturation of Ca and P. Why?

A

Pyrophosphate found in all tissues prevent precipitation of Ca except in bone

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5
Q

Calcium Salt precipitation

A

Hydroxyapatite crystal formation is allowed in bone because hydroxyapatite is neutralized by osteoblast alkaline pyrophosphatase

May precipitate abnormally in other tissues due to lack of inhibitors
Precipitate of the arterial walls causes atherosclerosis
In degenerating tissues or blood clots, calcium precipitation inhibitors are degraded or diffuse out allowing precipitation

Calcium salt precipitates on the surface of collagen fibers
Converted to bydroxyapatite crystals or
Mixed with other salts to make amorphous compounds (serves as a ready source of Ca)

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6
Q

Osteoblasts

A

Secrete collagen monomers and ground substance

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7
Q

Collagen monomers

A

Form collagen fibers making osteoid tissue
Cartilage like: Ca salt precipitates
Osteoblasts become trapped and become osteocytes

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8
Q

Bone Remodeling

A

Continually being modified
Deposited by osteoblasts (outer surfaces of bone and bone cavities; new bone constantly being formed)

Ca mobilized by osteoclasts
Secrete proteolytic enzymes and acids to digest bone matrix and solution of salts
Controlled by parathyroid hormone

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9
Q

Stress control of deposition

A

Allows compensation for
strength in proportion to compression load
Shape is rearrangedfor support of mechanical force
Replacement of old brittle bone
Exercise stimulates osteoblast deposition

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10
Q

Effects of fracture

A

Maximally activates osteoblasts
increased osteoprogenitors –> osteoblasts
Results in: Bulge of osteoblastic tissue (may be resobred or become a callous), new bone matrix, deposition of calcium salts between ends = callus

surgical pinning of bone induces osteoblast activity and increased speed of healing

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11
Q

Calcium

A

Normal concentration 8.8-10.4 mg/dl in ECF

Key role in 
Muscle contraction
Hemostasis
Neurotransmission
Neurons are very sensitive to changes in Ca concentration

Hypercalcemia causes depression
Hypocalcemia causes excitability

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12
Q

Storage of calcium

A

0.1% total body calcium is in the ECF
1% is intracellular (cytoplasm has less but Ca is stored in the organelles until used in signal transduction)
Remainder stored in the bone

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13
Q

CA may be mobilized from

A

Amorphous compounds in the bone
Liver
GI Tract
rapid buffering system that may take affect as quickly as 30-60 mins

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14
Q

Phosphate

A

<1% ECF, ~15% intracellular, ~85% stored in the bone
Role of ATP, Second Messenger, (DNA, RNA, phospholipids), Enzyme phosphorylation
Assists intracellular acid-base balance (H2PO4 -> HPO4 + H+)

Inorganic phosphate is regulated by parathyroid hormone. Extracellular concentration of Pi is inversely related to Ca+

Needed for ATP and energy BAYBAY

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15
Q

Calcium absorption

A

30% absorption rate from diet
This rate drops without vitamin D
90% of Ca is excreted

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16
Q

Phosphate absorption

A

Easily absorbed through GI (100%)

Excreted through feces

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17
Q

Parathyroid hormone

A

4 parathyroid glands are near the posterior aspect of the gland
Removal/destruction of 2 glands has no effect. 3 glands yields hypoparathyoidism and the other glands will undergo hypertrophy

Chief cells secrete ParaThyroid Hormone (granular). Oxyphil cells are inactive chief cells.

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18
Q

Parathyroid Hormone over/underactivity

A

Main action is to control ECF Ca and Pi via
intestinal reabsorption, renal excretion/absorption, ECF:Bone exchange

Overactive parathyroid causes hypercalcemia (osteoporosis)
Underactive parathyroid causes hypocalcemia (tetany due to excitability of NS)

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19
Q

PTH controlled by calcium concentration

A

With decreased Ca, PTH release is stimulated

PT gland will hypertrophy if calcium deficiency persists
The Ca receptor changes affinity with the concentration of Ca

Increased Ca inhibits the PT gland and decreases PTH
Gland will atrophy with excess calcium (high diet or inappropriate bone absorption)

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20
Q

Calcium deficiency occurs with ___

A

Rickets: decreased dietary intake of Ca
Pregnancy: Increased fetal demand for Ca
Lactation: Ca is required to make milk

When calcium deficient GPCR becomes a high affinity receptor for Ca and teh receptor preferentially signals via cAMP

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21
Q

PTH actions via GPCR

A

Increase Ca and Pi release from bone
Cause release of bone salts via osteolysis
Rapid activation and proliferation of osteoclasts

Decreased Ca excretion from kidney
Reabsorption of Ca at the distal renal tubule and collecting ducts

Increased Pi excretion from kidney
also sodium potassium and amino acids

Hydroxylation of 25-OH Vitamin D to active form Vitamin D (via vitamin D hydroxylase)
This causes increased Ca and Pi absorption in GI

22
Q

AA release from bone

A

AA may also be released from bone in addition to Ca and P

Therefore osteoporosis may occur with starvation or malnutrition

23
Q

Excess calcium causes

A

causes platelets to aggregate and form a clot

Overactive nervous stimulation to lead to anorexia (aches, pain)
calcium antagonized at the ADH receptor = polyuria
Diuresis = polydypsia

24
Q

Neuron sensitivity to Ca

A

Hypercalcemia causes depression of PNS
can cause excitability of the CNS that if left untreated can lead to the depression and desensitization of NT receptors

Hypocalcemia causes excitability of the CNS

25
Q

general malaise, aches, pains, anorexia, weight loss. Polyuria and polydipsia.
Diagnosis?

A

Urinalysis is negative for glucose which rules out DM.
Serum calcium levels at 16.4 mg/dl. All other tests normal.
In this case the patient is a woman with multiple breast fed infants.
Hyperparathyroidism causing hypercalcemia.

26
Q

GPCR of parathyroid gland

A

Will either stimulate adenyl cyclase OR phospholipase C
One pathway favored over the other based on conformation of GPCR
PLC (DAG and IP3) inhibits PTH secretion
adenyl cyclase (cAMP) leads to increased PTH secretion

under normal levels the secretion is basal

27
Q

PTH Pathway

A

At the levels of bones stimulate cAMP through a GPCR

28
Q

How to increase serum calcium

A

PTH is secreted by prarthyroid hormone
PTH conserves Ca and excretes Pi at the kidney
PTH activates osteoclasts

PTH activates Vitamin D hydroxylase which makes active form Vitamin D
vitamin D goes to the intestine to absorb CA, P, and Mg
Low P stimulates vitamin D

29
Q

Pi excretion at kidney

A

PTH binds GPCR at osteoclasts stimulating the release of hydroxyapatite
Releases BOTH Ca and P

30
Q

Decrease serum calcium

A

High serum calcium causes signaling of PLC which creates IP3 that inhibits the release of PTH
PTH actions on bone kidney and indirectly on the GI are then absent and CA is excreted via Gi and kidney

31
Q

Hypoparathyroidism

A

Osteocytic resorption of exchangeable ca decreases
Osteoclasts become inactive
Level of Ca in the ECF decreases
Bones remain strong

32
Q

Tetany occurs when ___

A

serum concentration falls to 6mg/dl with death at 4

33
Q

Hypoparathyroidism treatment

A

Vitamin D supplementation at 100,000 IU (this is most effective in patients that have some functioning PTH)
May supplement with active form vitamin D (in complete lack of PTH)

Calcium supplementation
Flooding the GI tract FORCES absorption of GI tract

34
Q

Hyperparathyroidism

A

Benign or malignant tumor causes increased secretion of PTH
More common in women because of lactation and pregnancy
Hyper PTH causes osteoporosis (High serum Ca)
Decreased Pi due to excretion at the kidney

In minld hyperPTH the osteoclastic activity can be offset by compensatory osetoblastic activity

35
Q

Identifying Hyperparathyroidism

A

With the increased osteoblastic activity seen there will be higher alkaline phosphatase.
Observe higher serum ALP
In severe HyperPTH osteoclast activity will overwhelm osteoblast yet ALP will be high

36
Q

Associated maladies of Hyperthyroidism

A

Fracture from slight trauma
Osteo fibrosa cystica (large punched out cystic areas, giant cell osteoclast tumors)

Kidney stones
Increased concentration of Ca and P in alkaline urine
CaP crystals form stones. may lead to calcification of kidney tubules that prevents H+ secretion (OH NO ACIDOSIS)

37
Q

Hypercalcemia 10.2-15mg/dl

A 
Depressed NS
Muscle weakness
Constipation
Abdominal pain, peptic ulcer
Lack of apetite
Diastolic blood pressure abnormalities
Joint pain osteoporosis
Anxiety
Memory Loss
Fatigue
38
Q

Hypercalcemia >17mg/dl

A

Parathyroid poisoning and metatstatic calcification
kidneys cannot excrete enough calcium

Calcium phosphate crystals precipitate and deposit in 
Alveoli of lungs
Tubule of kidneys
Thyroid gland
Mucosa of stomach
Walls of arteries
Death (with increased phosphate)
39
Q

Secondary hyperparathyroidism

A

Elevated PTH due to hypocalcemia in absence of parathyroid gland abnormality

Causes
Vitamin D deficiency
Chronic renal disease
BOTH of these means that there is no PTH from the expression of vitamin D hydroxylase

40
Q

Calcium:PTH relationship

A

Ca low and PTh high = normal
Ca low and PTH normal or low = hypoparathyroidism
Ca high and PTH high = primary hyperparathyroidism
Ca normal and PTh high = secondary hyperparathyroidism (Vitamin D deficiency or Chronic renal disease)
Ca high and PTH low = working Ca regulation system

41
Q

Calcitonin

A

Generally opposes PTH actions
Produced by parafollicular cells of thyroid

Used as a tumor marker for medullary thyroid adenocarcinoma

42
Q

Calcitonin function in Calcium Homeostasis

A

Serum calcium decreases
Suppresses reabsorption of osteoclasts. Inhibits release of Ca and Pi into blood keeping it in bone
Inhibits tubular reabsorption of Ca leading to increased rates of urine loss

43
Q

Calcitonin feedback

A

Part of feedback control of Ca concentration but is weaker than PTH.
Only slightly effects GI and kidney reabsorption of Ca
PTH overrides Calcitonin effect

44
Q

Calcitonin has minor actions in adults

A

Removal of thyroid does not require supplementation of calcitonin
Effect in children is greater due to increased bone remodeling
Calcitonin may be important in decreasing Ca absorption at the kidney

45
Q

Vitamin D Effects

A

Main effect is to increase absorption of Ca and Pi from GI to ECF. Contribute to feedback regulation of Ca and Pi. Synergizes with PTH to excrete Pi at kidney

Increases ca and Pi absorption from GI tract. Increases Ca binding protein in intestinal cells, ATPase in GI cell, alkaline phosphatase in GI cell

46
Q

Effect of Ca on Vitamin D

A

Inversely affected by serum Ca levels
Increased Ca prevents formation of active D
Ca2+ level < 9-10 mg/dl induces PTH secretion and activity of renal vitamin D hydroxylase
Ca2+ level > 9-10 mg/dl inhibits PTH

47
Q

Synthesis of vitamin D

A

Solar irradiation of 7-dehydrocholesterol to Cholecalcifero
Cholecalcifero to 25hydroxyvitamin D in liver
1,25-dihydroxyvitamin D [1,25(OH)2D3] (kidneys)
Conversion to active form requires PTH

48
Q

Requirements for Vitamin D synthesis

A

Appropriate sun exposure prevents deficiency. Dietary vitamin D, D2 from plants and D3

49
Q

Vitamin D actions

A

Vitamin D circulates bound to transcalciferin (TC). In the cell, it binds the Vit D receptor and dimerizes with other receptors, notably the retinoic acid receptor to regulate gene expression

Active D also stimulates production of anti-microbial peptides in intestinal epithelial cells, neutrophils, and macrophages
Maintains healthy numbers of T cells in the immune system
Inhibits pro-inflammatory activity of T other immune cells…high incidence of autoimmunity such as MS, RA, type I diabetes in Pacific NW due to less D

50
Q

Active D increases the active absorption of Ca2+ from the intestinal lumen of the gut via

A

Active uptake of Ca2+ from the luminal brush border of the enterocytes
Binding of Ca2+ to a calcium-binding protein (CaBP)
Translocation of the complex to the basolateral surface of the cell

51
Q

Vitamin D and Mental Health

A

Connection between vitamin D and depression, autism, and other forms of mental health disorders.
25-hydroxyl D levels less than 20 ng/dL indicate deficiency.
Vitamin D response elements have been found in genes required for serotonin biosynthesis (tryptophan hydroxylase 2), for oxytocin, oxytocin receptor, and arginine vasopressin receptor (for social interactions), and leptin.

Physiology II (4 decks)

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