Fluids & electrolytes readings

Why are calcium, phosphorus and magnesium refer to as “bone minerals”?

About 98% of the calcium, 80% of the phosphorus,

and 65% of the magnesium in the body are in the skeleton.

Why do we need these minerals for babies in the NICU?

What population of kids are even more suseptible?

Because after birth, nutrient intake from most enteral sources, especially unfortified human milk, is below the amount needed to achieve this level of mineral retention.


This risk is greatest in infants with chronic illnesses such as bronchopulmonary dysplasia

What are the other roles of these minerals apart from bone formation?

1. They act as transport across membranes, activation and inhibition of enzymes

2. Intracellular regulation of metabolic pathways.

3. Secretion and action of hormones, blood coagulation, muscle contractility, and nerve conduction. 

What are some other use of Phosphorus & Magnessium?

Phosphorus 
- Adenosine triphosphate, nucleic acids, and cell and organelle

membranes.

Magnesium (an essential intracellular cation)

• Critical in energy-requiring metabolic processes

• Protein synthesis, membrane integrity, nervous tissue conduction

• Neuromuscular excitability, muscle contractility, hormone

secretion, and intermediary metabolism.

How is Calcium categorized?

• 50% of total serum calcium is in the ionized (represents

the biologically active component of the total serum calcium concentration)

• Another 8% to 10% is complexed to

organic and inorganic acids (e.g., citrate, lactate, bicarbon-

ate, sulfate, and phosphate).

• The ionized and complexed calcium fractions are the diffusible portion of circulating calcium.

• 40% of serum calcium is protein bound (not biologically

  active but helps as a reseve) primarily to albumin and to globulins.

• Ionized calcium is the only physiologically active

fraction.

What are the hormone that regulates Calcium and how?

1. Parathyroid hormone (PTH) and calcitriol
   By increasing serum Ca+

2. Calcitonin, which decreases serum calcium.

Are Calcium high at birth or low…and why?
What changes could affect Calcium trends?

Both total & ionized calcium are high at birth but decrease sharply during the first hours of life to reach a nadir at 24 hours and increase progressively thereafter up to the end of the first week of life.

Calcium might also temporary decrease due to distribution of calcium between ionized and bound fractions.


When phosphate, citrate, or bicarbonate (in extracellular fluid) increases, the proportion of bound calcium increases while ionized calcium decreases.

Alkalosis also increases the affinity of albumin for calcium and thereby decreases the concentration of ionized calcium. In contrast, acidosis increases the ionized calcium concentration by decreasing the binding of calcium to albumin. 

Why does preterm babies not get enough Ca + from their mother ?

What is the main regulator of ionized Calcium? And where is it made?

Even though Calcium is transferred to baby via placental, about 80% of calcium accumulates during the third trimester when fetal skeletal is mostly mineralised.

Parathyroid hormone–related protein (PTHrP) (made by placental & fetal parathyroid glands)

What are these enymes for
- 5-hydroxyvitamin D-1α hydroxylase
- 1,25-dihydroxyvitamin D-24 hydroxylase?

1. Two key enzymes for vitamin D metabolism.

Where is Calcium absorbed and where is it ionized?

• Ionized in the stomach due to acidic pH

• Absorbed in the small intestine (active and passive processes with the help of Vitamin D as it carries calcium-binding proteins)

Why does fat intake affect Calcium absorption? What other factor affect Calcium absorption?

Fat intake after hydrolysis of triglyceride impairs Calcium absorption

Some EBM or formula has bile salt- stimulated lipase or total saturated long-chain fatty acid that when replaced with medium-chain triglycerides, Calcium absorption increases

Medications
- Glucocorticoids and Phenytoin (inhibits intestinal absorption)
- Phenobarb (basically any meds that interfere with Vit D metabolism)

How is Calcium excreted / balanced ?

How does duiretics affect Ca + reabsorption?

Between intestinal absorption, renal fecal excretion and sweating through the skin…thats how Ca+ is maintained
When it’s too low, it is reabsorbed in the distal convoluted tubule which is regulated by regulated by PTH and 1,25(OH)2D3


Furosemide increases renal calcium losses and is a risk factor for neonatal nephrocalcinosis.
Thiazides increase renal tubular calcium reabsorption, thereby reducing calciuria.

What determines if Ca+ needs to be re-absorbed or needs to increase it loss and why?

In adults, most of the Ca+ is reabsorbed in the renal

tubule but in preterm there are few differences
1. Renal function is not fully developed

2. Mineral requirements for growth

are very high

3. Renal calcium load is based on the difference between net absorption and net bone and soft

tissue retention.

The main determinant of the urinary loss of calcium in preterm and term neonates is phosphorus depletion and urinary excretion. 

Why is there an increased in urinary excretion of Calcium when babies are on exclusively EBM?

• Babies on EBM have low urinary phosphate excretion (because EBM has low phosphate) so Ca+ is increased or high urinary excretion

• Calcium & Phosphorus are inversely proportionate When human milk is provided

• But when human milk is supplemented with

phosphate, significant phosphaturia appears while calciuria

decreases to a minimum level.

Lesson: When you see hypercalciuria, you can guess that there is a relative phosphate depletion which means there is not enough phosphate demand necessary for skeletal mineralization

How much of Calcium is recommended for intake?

Calcium intake of 150 to 220 mg/kg/day for infants

receiving 120 kcal/kg/day of feeding.

Where is phosphorus usually present? and what are some functions of phosphorus? What does deficiency in phosphate mean?

• Phosphorus is present in the soft tissues,

mainly in the form of phosphate esters, and in extracellular

fluid in the form of inorganic phosphate ions.

• It helps with energy metabolism, membrane composition, nucleotide structure, cellular signaling, and bone mineralization.

• Deficiency of phosphorus results muscle weakness, impaired leukocyte function, poor linear growth, and abnormal bone metabolism.

When we measure or do blood work for Phosphorus, which one do we measure?

What is a big difference between Phosphorus & Calcium (other than their functions?)

We measure the inorganic phosphorus

- 85% of inorganic phosphorus is ionized circulating as monohydrogen or dihydrogen phosphate
- 5% is complexed with sodium, magnesium or calcium
- 10% is protein bound

Phosphorus concentration varies widely depending mainly on intake and renal excretion but also age, gender, pH, and a variety of hormones. 

How is Phosphorus absorbed ?

• Intestinal phosphorus absorption takes place primarily in the

duodenum and jejunum.

• It occurs by either an active, sodium-dependent transcellular process and passive diffusion through the paracellular pathway.

What are the hallmarks for the following?

- High PTH
- High FGF23
- Renal rickets

What three factors controls phosphorus reabsorption?

• Hallmarks of high PTH activity are hypophosphatemia, phosphaturia, disturbance in vitamin D metabolism, and low calcium.

• Hallmarks of high FGF23 activity are hypophosphatemia, phosphaturia and low 1,25-OH2D,

• Hallmarks of renal rickets are hypophosphatemia and phosphaturia with high circulating 1,25-OH2D.
  
  
  1. High PTH activity

• 2. High FGF (fibroblast growth factor) 23

• 3. Renal defects that lead to inorganic phosphate (Pi) wasting.

What makes preterm infants have higher risk of developing hypophosphate?

Where in the kidneys are phosphorus re-absorbed?

Preterm infants have an increased fractional excretion of phosphate and are at a greater risk for developing signs and symptoms of phosphate deficiency.


The bulk of filtered phosphate is reabsorbed in the proximal tubule through sodium-dependent transporters, the Na phosphate cotransporters 

What are some functions of Magnesium?

Magnesium is the second-most abundant intracellular cation, playing a crucial role in many physiologic functions.
- It is critical in energy requiring metabolic processes

• Protein synthesis, membrane integrity, nervous tissue conduction, neuromuscular excitability

• Muscle contraction, hormone secretion, and intermediate metabolism.

How is MAGNESSIUM ABSORBED?

• Primarily in the proximal intestine through both passive and active

• And in the kidneys - The primary site for magnesium reabsorption is the thick ascending limb of the loop of Henle,

What hormones affect Mg reabsorption and how?

Hormones

• Calcitonin

• Glucagon

• Vasopressin

• PTH

• Insulin all increase the tubular reabsorption of magnesium.
  
  Non hormonal factors

• Concentration of magnesium in the tubular lumen

• Acid-base equilibrium

• Plasma concentrations of potassium and inorganic

  phosphate.

• Metabolic acidosis also increases the urinary excretion of magnesium. 

How does PTH affect Calcium, Phosphorus?

• PTH increases serum calcium concentrations by increasing

bone resorption and renal calcium reabsorption and indirectly by increasing renal synthesis of 1,25(OH)2D3, thereby increasing intestinal calcium absorption.

• PTH lowers serum phosphorus concentrations through its phosphaturic effect on the renal proximal tubule. This action minimizes the possibly adverse effect of hyperphosphatemia

related to bone resorption on calcium homeostasis.


Serum calcium concentration regulates PTH secretion; high concentrations inhibit the secretion of PTH, and low concentrations stimulate it. 

What is the relationship between Vit D & PTH?

Vitamin D and its metabolites 25-OHD and 1,25-OH2D, acting through VDRs, decrease the level of PTH mRNA.

How does Maternal hyperparathyroidism affect baby?

Maternal hyperparathyroidism results in maternal hypercalcemia, which leads to fetal hypercalcemia and suppression of fetal and neonatal parathyroid glands. Conversely, untreated maternal hypoparathyroidism leads to maternal hypocalcemia, fetal hypocalcemia, and secondary fetal and neonatal hyperparathyroidism.

What are the expectations of PTH varily with age? (Term, preterm, VLBW, infants of diabetic mothers, infants with perinatal depression)

Newborn - Serum calcium in the newborn decreases (due to abrupt termination of the maternal calcium supply) and serum PTH increases correspondingly.

Both term and preterm infants may show a PTH response to falling serum calcium.

Infants with VLBW have a decreased PTH surge compared with full term infants.

Infants of diabetic mothers (IDMs) may have impaired PTH production during the beginning days of life.

Infants with severe perinatal depression may also have decreased PTH responses to hypocalcemia.

How is Vit D synthesized?
What is the difference between Vit D3 & Vit D2?

• Vit D is synthesised in the skin after exposure to sunlight, it is then absorbed in duodenum & jejunum.

• D3 is when its absorbed from animal sources & Vit D2 aka ergocalciferol is when it’s absorbed from vegetables

• Wheter Vit D3 & D2, all vit D is then hydroxylated in the liver to form vitamin D3 (25(OH) - which is the actual Vit D we test for

• Vitamin D3 (25(OH) is finally hydroxylated in the kidney to form the final active metabolite,

25-hydroxyvitamin D3-1α-hydroxylase (1α-hydroxylase),

Why is Vit D necessary to maintain Calcium & Phosphorus homeostasis ?

• We already know the relationship between Ca & Phosphorus but 1,25(OH)2D3, the metabolite of Vit D actually enhances the synthesis of calcium transporters and calcium-binding protein in the intestine.

• It also increases calcium reabsorption in the distal nephron segments by increasing the expression of the epithelial calcium influx channel.

What are some of the disadvantages of Vit D deficiency during pregnancy for the child / baby?

What about vit D deficiency in the mother?

• Abnormal skeletal metabolism 

• Osteopenia

• Possible fractures during the neonatal

  period.

• Reduced bone size & BMC

• Influence on fetal skeletal development
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• Increased risk for preeclampsia

• Insulin resistance

• Gestational diabetes mellitus

• Primary cesarean delivery

Why do we test for 25(OH)D?

In what cases would it be considered to increase Vit D dose - from the regular daily intake of 400 IU and why?

Serum or plasma 25(OH)D concentration is a useful vitamin D biomarker reflecting vitamin D supply (exposure) over time.
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Since vitamin D is metabolized in the liver, medications such as anticonvulsants (Phenobarbital and diphenylhydantoin) increases Vitamin D’s hepatic catabolism and requirements.

What are the purpose of Calcitonin?

• Secreted by thyroid gland, it’s main goal is to overall effect of calcitonin is to decrease serum calcium and phosphorus concentrations.

• Suppresses the secretion of PTH and regulates renal tubular calcium excretion. 

• It also decrease osteoclastic bone resorption and the amount of calcium and phosphorus released from bone. 

What are some factors that determine growth and bone density of the fetal in utero?

Growth
- Not only protein & energy supply but also hormones such as insulin, IGF1 & 2

Bone formation, mineralization, and structure
- PTH

• Vitamin D

• Calcitonin

• Genetics and physical activity

• Reduced calcium supply, vitamin D deficiency, ethanol

  consumption, and smoking during preganancy affects fetal skeletal development and causes low weight related to gestation

• Also bigger babies to diabetic mothers

What is physiologic osteoporosis of infancy?

Physiologic osteoporosis of infancy is a normal, temporary drop in bone mineral density that occurs in healthy, full-term babies between 2 and 6 months of age. It happens because an infant's bones are growing in length and volume faster than their body can deposit calcium to pack them densely. Despite the alarming name, it is a completely harmless, symptom-free developmental phase—not a disease—and it resolves naturally on its own by the end of the first year as bone mineralization catches up.