Lect 29 Flashcards
Calcium is essential for:
1. Formation of ______ and _____
* 99% of calcium is found in bones
2. Enzyme co-factor
3. Such as the coagulation cascade
4. Signal transduction
5. Neurotransmitter release
6. Muscle contraction
Calcium is essential for:
1. Formation of bone and teeth
* 99% of calcium is found in bones
2. Enzyme co-factor
3. Such as the coagulation cascade
4. Signal transduction
5. Neurotransmitter release
6. Muscle contraction
Phosphorus is essential for:
1. Generating ATP
* Component of DNA, enzymes, and hormones
* Buffering to help maintain normal blood pH
* Part of bone matrix just like Calcium
2. Renal Excretion is controlled by PTH
* PTH promotes loss of Phosphorus in urine to keep balance.
when analyzing phosphorous, we always have to look at Ca at the same time to understand what is happening
Magnesium
1. Primarily _____cellular _______
2. Cofactor in many enzymatic reactions: ATP
3. Required for protein and nucleic acid synthesis
4. Concentration regulated by intestinal absorption and renal excretion
* Influenced by PTH and vitamin D
5. Serum Mg - balance between intake (diet) and excretion:
* Most lost in feces
* Milk is high in Mg
* kidney can excrete excess Mg but cannot conserve enough Mg in deficiency
6. Important in nerve conduction
When we measure serum mg, it is a poor indicator what MG is doing in the body. Most body Mg is stored in bones.
Magnesium
1. Primarily intracellular cation
2. Cofactor in many enzymatic reactions: ATP
3. Required for protein and nucleic acid synthesis
4. Concentration regulated by intestinal absorption and renal excretion
* Influenced by PTH and vitamin D
5. Serum Mg - balance between intake (diet) and excretion:
* Most lost in feces
* Milk is high in Mg
* kidney can excrete excess Mg but cannot conserve enough Mg in deficiency
6. Important in nerve conduction
Calcium & Magnesium
* Calcium-sensing receptors (CaSR) regulate the response of parathyroid chief cells, C-cells of the
thyroid gland, and renal epithelial cells
* Stimulation of CaSR (due to increased calcium) decreases NaCl, calcium, and magnesium reabsorption in the proximal convoluted tubule of the kidneys
* Magnesium is necessary for the CaSR to function
* Severe hypomagnesemia decreases PTH secretion
Calcium & Magnesium
* Calcium-sensing receptors (CaSR) regulate the response of parathyroid chief cells, C-cells of the
thyroid gland, and renal epithelial cells
* Stimulation of CaSR (due to increased calcium) decreases NaCl, calcium, and magnesium reabsorption in the proximal convoluted tubule of the kidneys
* Magnesium is necessary for the CaSR to function
* Severe hypomagnesemia decreases PTH
secretion
Calcium & Phosphorus homeostasis are closely related and intertwined.
1. What three major hormones regulate Calcium and Phosphorous levels?
2. What organs participate in these processes?
Calcium & Phosphorus Homeostasis
* Closely related and intertwined
* Three major regulatory hormones:
1. Parathyroid hormone (PTH) (↑Ca, ↓Phos)
2. Vitamin D → Calcidiol → Calcitriol (↑Ca, ↑Phos)
3. Calcitonin (↓Ca)
* Organs of interest:
* Intestine (absorption)
* Kidney (resorption)
* Bone (Ca, Phos storage)
Calcium & Phosphorus
* Part of routine chemistry profile
* Should be interpreted together
* Controlled by the same hormones
* Concentrations affect each other
Parathyroid Hormone (PTH)
* Produced by _____ cells in the ________ gland. ____-to-____ regulation of _______
–> Function:
1. To _______ plasma ______ Ca2+ (_____-to-_____ regulation)
2. To _______ plasma phosphorus
–> Secretion:
* Stimulated by ____ plasma calcium concentrations
* ________ by low plasma phosphorus concentrations
Parathyroid Hormone (PTH)
* Produced by chief cells in the parathyroid gland
Minute-to-minute regulation of calcium
* Function:
* To Increase plasma iCa2+ (minute-to-minute regulation)
* To Decrease plasma phosphorus
* Secretion:
* Stimulated by low plasma calcium concentrations
* Inhibited by low plasma phosphorus concentrations
Parathyroid Hormone (PTH)
–> PTH Promotes __ serum Calcium and ___Phosphorus
* Calcium _______ from bone (enhanced by ?)
* Renal _______ of calcium
* Formation of ______ Vit D (__Ca) in the kidney
* Increased calcium _______ from the intestine
–> PTH Inhibits
* phosphorus resorption by the ______ inducing an increased phosphorus secretion in the ____
Parathyroid Hormone (PTH)
* PTH Promotes ↑Calcium and ↓Phosphorus
* Calcium resorption from bone (enhanced by Vit D)
* Renal resorption of calcium
* Formation of active Vit D (↑Ca) in the kidney
* Increased calcium resorption from the intestine
* PTH Inhibits
* phosphorus resorption by the kidney inducing an
increased phosphorus secretion in the urine
Basically INCREASE SERUM CALCIUM
DECREASE SERUM Phosphorus
Calcitonin
* Produced by ________ cells (__ cells) in the _______ gland in response to _________
–> Net effects of calcitonin:
* _______ serum calcium
* Decreased bone ______ (inhibits _______ activity)
* Decreased calcium absorption in the ___ tract
* ________ calcium reabsorption in the kidneys
* _________ serum phosphorus
* Increased phosphorus ______ by the kidneys
Calcitonin
* Produced by parafollicular cells (C cells) in the thyroid gland in response to hypercalcemia
* Net effects of calcitonin:
* Decreased serum calcium
* Decreased bone resorption (inhibits osteoclast activity)
* Decreased calcium absorption in the GI tract
* Decreased calcium reabsorption in the kidneys
* Decreased serum phosphorus
* Increased phosphorus excretion by the kidneys
Vit. D
* _________l is the metabolically active form of vitamin D
–> Net effects:
1. _______ serum calcium and phosphorus
- Effects are ______ for calcium than phosphorus
3. Increases calcium and phosphorus absorption in the ____ tract
4. Facilitates _____ action on bone –> increased serum calcium
Vit. D
* 1,25-dihydroxycholecalciferol is the metabolically active form of vitamin D
–> Net effects:
1. Increased serum calcium and phosphorus
- Effects are greater for calcium than phosphorus
3. Increases calcium and phosphorus absorption in the GI tract
4. Facilitates PTH action on bone –> increased serum calcium
IMPORTANT
Calcium in plasma:
1. 50-55% is ________ Ca++
- _____ form, _____ regulated
2. 35-45% is _____ bound
- 80% is bound to _____
- 20% bound to other ______
3. 5-10% complexed with _____ (4?)
Measured two ways:
1. Total Calcium: (CHEM PANEL)
_______, _____-bound, and ______ calcium. Reported on the _______ panel as Calcium.
2. Ionized Calcium:
Measured on calcium _____ (specialty labs) and some point-of-care instruments
(e.g. _____)
If albumin decreased
“apparent hypocalcemia” and vice versa
IMPORTANT
Calcium in plasma:
1. 50-55% is ionized (iCa)
* active form, tightly regulated
2. 35-45% is protein bound
* 80% is bound to albumin
20% bound to other proteins
3. 5-10% complexed with anions
(bicarb, lactate, citrate, phosphate,
etc)
Measured two ways:
1. Total Calcium: (CHEM PANEL)
Ionized, protein-bound, and complexed calcium
Reported on the chemistry panel as
Calcium
2. Ionized Calcium:
Measured on calcium panels (specialty labs) and some point-of-care instruments
(e.g. iSTAT)
If albumin decreased
“apparent hypocalcemia” and vice versa
Ionized Calcium (iCa)
1. Only form of Ca that is biologically _____ in bone formation, _______ activity, ______ processes, and blood _______
2. Proportion of tCa that is ionized is affected by ____-____ balance:
- ______ increases iCa concentration –> Ca _______ from albumin
- Alkalosis ______ iCa concentration –> More Ca ______ to albumin
3. iCa can be measured on ______ or _________ ______
* Directly measured using ion-sensitive ______ (direct ___________)
* Blood ___ analyzers or other point-of-care analyzers
Ca can be altered if you handle sample poorly _____ collection or if you put in wrong ____ (contaminate with EDTA - 4?)
Ionized Calcium (iCa)
1. Only form of Ca that is biologically active in bone formation, neuromuscular activity, biochemical processes, and blood coagulation
2. Proportion of tCa that is ionized is affected by acid-base balance:
* Acidosis increases iCa concentration
* Ca released from albumin
* Alkalosis decreases iCa concentration
* More Ca bound to albumin
3. iCa can be measured on serum or heparinized plasma
* Directly measured using ion-sensitive electrodes (direct potentiometry)
* Blood gas analyzers or other point-of-care analyzers
Ca can be latered if you handle sample poorly after collection or if you put in wrong tube (contaminate with EDTA - hypocalcemia, hypomagnesemia, phosphate altered, hyperkalemia
Protein-bound Calcium
* Hypoalbuminemia leads to decrease in ____ (due to decreased ________- bound Ca)
* IMPORTANT: iCa remains ______ – how to differentiate between hypoalbuminemic hypocalcemia and “true” hypocalcemia (decreased ____)
* If hypoalbuminemia is present, correction formula can help exclude the possibility of “true” hypocalcemia using a patient’s biochemistry panel:
* FYI: Adjusted calcium (mg/dL) = 3.5 – albumin (g/dL) + measured
calcium (mg/dL)
Protein-bound Calcium
* Hypoalbuminemia leads to decrease in tCa (due to decreased protein- bound Ca)
* IMPORTANT: iCa remains within RI – how to differentiate between hypoalbuminemic hypocalcemia and “true” hypocalcemia (decreased iCa)
* If hypoalbuminemia is present, correction formula can help exclude the possibility of “true” hypocalcemia using a patient’s biochemistry panel:
* FYI: Adjusted calcium (mg/dL) = 3.5 – albumin (g/dL) + measured
calcium (mg/dL)
What are the DDx of Hypercalcemia?
D Vitamin D Toxicity
R Renal Failure
A Addison’s disease
G Granulomatous Disease
O Osteolytic disease
N Neoplasia
S Spurious
H Hyperparathyroidism
I Idiopathic (Cats)
T Toxins
IMPORTANT –> For vet med: neoplasia (#1 cause of hypercalcemia and primary hyperparathyroidism is the second one).
Granulomatous can be one too (e.g. blastomycosis, coccidiomycosis). Some toxins can also induce too
What are the clinical signs of hypercalcemia in dogs?
Clinical signs of hypercalcemia in dogs
* Shivering
* Lethargy
* Depression
* Inappetence
* muscle weakness
* Constipation
* Bradycardia
* Arrhythmias
* PU/PD
* Vom/ Diarrhea
