Physiology of Calcium Balance

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T or F
If PTH is too high calcium is in the urine

T

Diffusion

movement of particles from a higher concentration to a lower concentration because the temperature is above 0K

Order the following salts in increasing order of concentration

Sodium>chloride>potassium>calcium>magnesium
Na>Cl>K>Ca>Mg

If you weigh 70kg, how many pounds and liters of water do you carry?

70kg=154lbs=40L
In other words, water makes up 60% of your body

What are the 4 main body fluid compartments in which water is divided?

Intracellular (25L)
Plasma (3L)
Interstitial (11L)
Transcellular (1L)

What percentage of the total body water is interstitial?

16% (approx. 11 L)

Plasma, Interstitial, and Transcellular are referred to as what compartment?

Extracellular compartment

If the interstitial fluid in a 70kg man accounts for 11L, how much interstitial fluid is in an 100 kg man?

16L because intersitial fluid is 16% of TBW regardless of your weight

What is the total extracellular concentration of calcium (free and bounded)?

2.5mM

What is the intracellular concentration of calcium?

.0001mM

Briefly describe the process of Muscle contraction

1. Electrical signal: motor nerve produces an action potential that conveys that signal to the end of the nerve where the nerve touches the muscle.
2. Chemical signal: Acetylcholine is released from the terminal axon
3. Muscle contraction: Neurotransmitter diffuses to the muscle and activates receptors on the surface of the muscle cell membrane to cause the muscle to generate its own action potential which then will cause contraction of the muscle (opens sodium fast channels to initiate action potential).

At rest the interior of cell are (positive/negative)?

Negative

Voltage Gated channel

Gate is most often closed but can be briefly opened by an abrupt change in cell membrane potential

T or F
The nerves can function properly to release Ach when calcium is maintained near 2.5 mM per liter in the ECF

T

Briefly describe the vesicle release of neurotransmitter

Electrical signal activates
Calcium channels open
Calcium enters the cell
vesicles dock/fuse
vesicles release NT
NT stimulates muscle

T or F
You can stimulate skeletal muscle without calcium because the muscle uses internal deposits to contract

T; calcium is used for release of Ach to stimulate muscle

Why is synaptic degradation important to muscle contraction?

Prevents continuous muscle contraction

Where is calcium stored in the muscle cell?

Sarcoplasmic Recticulum; when muscle is stimulated calcium is released from the SR

Briefly go over muscle contraction

At rest there is no calcium in the muscle cell. Troponin sites prevent actin/myosin binding. When calcium comes into the cell the active sites open for connection with myosin head.


Action potential comes down-->crosses neuromuscular junction-->releases calcium from SR-->calcium floods the cell; troponin becomes available to the myosin head-->myosin heads connect to the active site-->power stroke-->ADP and P are ejected-->Release energy

What is the primary initiator of skeletal muscle contraction?

Calcium release from SR

What induces the electrical signal within the heart muscle (what causes the electrical excitation of the heart muscle which causes the opening of voltage-operated calcium channels?

SA node

T or F
Heart depends on extracellular calcium coming into the heart muscle to cause complete actin/myosin contraction

T

Briefly go over how hormones use internal calcium concentrations to cause a final response.

Hormone binds to a surface receptor on the cell membrane.
Intracellular signal is initiated that causes release of calcium stored in the cell.
IP3 is released when a hormone stimulayes its membrane receptor and IP3 causes the release of stored calcium.
Receptor stimulation can open receptor operated calcium channels that allow calcium entry into the cell.
Released calcium activates the cell to preform action intended by hormone receptor.

Endocrine Hormone

substance released by an endocrine cell
travels through the blood stream
leaves the blood stream and then acts on target cells some distance away

What hormone primarily controls free calcium in the blood?

PTH

Which glands secrete calcitonin?

Parafollicular C Cells of the thyroid gland

Which hormones are active in the epithelium of the intestines and in the epithelium of the kidneys to help control calcium phosphate concentrations circulating in the blood?

PTH and vitamin D

Describe the extent effect of PTH's on the bone, kidney, and intestines.

Bone:A lot
Kidney: Most
Intestines: Indirect

Describe the extent effect of calcitonin's on the bone, kidney, and intestines.

Bone: A lot
Kidney:Minor
Intestines: None
(no known effects in kidney or intestines)

Describe the extent effect of Vitamin D's on the bone, kidney, and intestines.

Bone:Some
Kidney:Some
Intestines:most

During surgical removal of a parathyroid gland, sometimes the gland gets stuck beneath the __________ because of embryonic development

isthmus

PTH acts via hormone receptors that have ____ as a second messenger to cause the response inside target cells

cAMP

How does PTH indirectly stimulate osteoclasts? (p.39 in notes)

PTH activates osteoblasts to produce a hormone that stimulates osteoclasts to chew bone.

How many liters does the kidney filter each day and how many liters is saved?

Filters 180 liters; saves 179

What are the effects of PTH on the kidney nephron?

1. directly increases calcium reabsorption from the loop of Henle and indirectly from the distal tubule via activation of vitamin D through CaBP
2. decrease phosphate reabsorption by the proximal renal tubules by lowering the Tm (transport maximum) for phosphate reabsorption
3. activates renal 1-alpha hydroxylase in renal proximal tubule cells to form active Vitamin D

Briefly go over Vitamin D synthesis

7-dehydrocholesterol is converted to Vitamin D3 upon interaction with sunlight
Vitamin D3 in the blood is converted to 25-hydroxy Vitamin D3 by 25-hydroxylase enzyme in the liver.
25-hydroxy vitamin D3 is converted to 1,25-dihydroxy Vitamin D3 by 1-alpha hydroxylase

Why is Vitamin D important?

1, 25 dihydroxy Vitamin D3 causes the synthesis of calbindin D, the CaBP needed by kidney distal tubules and the GI tract to reabsorb calcium

What happens in Vitamin D synthesis when there is an absence of PTH?

enzyme 24-hydroxylase will form the inactive form of Vitamin D 24,25 dihydroxy Vitamin D3 from the precursor 25-dihydroxy Vitamin D3. PTH activates 1-alpha hydroxylase and inhibits 24-hydroxylase

Hypercalcemic Conditions

Primary Hyperparathyroidism
-due to increase plasma PTH
-leads to hypercalcemia and hypophosphatemia
-osteitis fibrosis cystica
-increased urinary calcium excretion/urinary stones
-muscle weakness, poor memory, depressopn
Treatment: surgical removal of PT gland

Hypercalcemia of Malignancy
-solid tumors secrete PTH related peptide
-produces same symptoms as primary hyperparathyroidism but PTH levels are decreased

Hypocalcemic conditions

Primary Hypoparathyroidism
-due to decreased PTH
-leads to hypocalcemia and hyperphosphatemia
-tetany (muscles stay contracted)

Pseudohypoparathyroidism
-rare, target tissue resistance to PTH
-same signs and symptoms as hypoparathyroidism but PTH is increased
-may be accomplished by developmental defects- retardation, short fingers, short stature

Vitamin D Deficiency Rickets Type 1

-rare genetic disorder
-due to deficiency of 1-alpha hydroxylase
-serum levels of 1,25 dihydroxy Vitamin D are decreased

Vitamin D Deficiency Rickets Type 2

-rare genetic disorder
-due to target tissue resistance to 1, 25 dihydroxy Vitamin D
-serum levels of 1,25 dihydroxy Vitamin D are increased

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