2.2. Regulation Of Calcium And Phosphate Flashcards
how is the majority of calcium stored in the body?
99% stored within the bones as calcium phosphate (hydroxyapatite). the rest is within extracellular fluid and very little calcium is stored intracellularly.
what are the 2 different groups of extracellular calcium?
Diffusible - can cross the glomerular membrane. Is either ionised Ca2+ or complexed with negatively charged molecules such as oxalate
Not diffusible - bound to albumin
what is free ionised calcium used for?
cellular processes e.g. neuronal action potentials, contraction muscles, hormone secretion, blood coagulation
where does calcium reabsorption in the nephron occur?
65% in the PCT
25% in the TAL
8% in the DCT
1.5% in the CD
how is calcium absorbed in the PCT? explain how this occurs
mainly by solvent drag (80%). Solvent drag is a paracellular pathway that occurs as the lumen of the PCT becomes more positive as potassium is secreted from the cells of the PCT via ROMK and Cl-/K+ cotransporters. the positively charged lumen repels the cations Magnesium and calcium and move between the lateral surfaces of the cells to be reabsorbed.
20% of calcium is reabsorbed through the transcellular pathway as calcium is actively pumped out of the PCT
where is phosphate stored in the body?
80% of the body’s PO4^3- is in bone and 20% in interstitial fluid
describe how phosphate is reabsorbed
reabsorption of phosphate occurs at the PCT alongside 2 molecules of Na+ via the phosphate sodium co-transporter on the apical membrane of tubular cells. 80% of filtered phosphate is reabsorbed and 20% is excreted
what causes the common symptom of itching in CKD?
An increase plasma concentration of phosphate. This occurs as there is a fall in GFR and therefore less phosphate is filtered and excreted.
how are calcium and phosphate inversely proportional?
calcium and phosphate will precipitate at saturation point to form calcium phosphate. As their concentrations in blood usually is very close to the saturation point, an increase in concentration of either of the ions will result in some precipitation of some of the calcium phosphate. As this precipitates some of the other ion is removed from the solution. Therefore if the concentration of one increases, the concentration of the other will decrease.
when there is a fall in plasma calcium concentration, what hormone is secreted?
Parathyroid hormone
what is calcitonin?
a peptide release from the thyroid that is secreted in response to elevated calcium levels. Prevents resorption of bone and opposes the action of parathyroid hormone
what action does parathyroid hormone have on the kidney
decreases phosphate reabsorption in the PCT, increases its excretion
increases the reabsorption of calcium in the distal tubules and reduces calcium excretion
- both act to increase plasma calcium levels
what is the action of parathyroid hormone in the intestines?
increases the formation of calcitriol ( 1,25 dihydroxycholecalciferol) which then increases the amount of calcium reabsorption
what is the action of parathyroid hormone of the bone?
promotes bone resorption to increase plasma calcium levels
what are some of the symptoms of hypocalcaemia?
Decreased Ca2+ results in neuromuscular excitability leading to tetany with convulsions, hand and feet muscle cramps and cardiac arrythmias
what are the causes of hypocalcaemia?
- CKD due to hyperphosphatasemia (if phosphate rises then calcium must fall proportionally) and low levels of activated vitamin D
- Hypoparathyroidism (low levels of parathyroid hormone secreted)
- Rickets and osteomalacia (low levels of vitamin D)
- Tissue injury (cells die and release intracellular phosphate) - Alkalosis, which reduces the amount of H+ available to bind to protein, so more Ca2+
can bind to protein. This results in decreased ionized Ca2+, although total Ca2+ remains
the same
what is the treatment of hypocalcaemia?
Treatment is with oral or intravenous calcium and patients with CKD will benefit from alfacalcidol, a vitamin D analogue
what are the symptoms and signs of hypercalcaemia?
Hypercalcemia makes cells less excitable resulting in slow reflexes, muscle weakness and constipation. Symptoms and signs of hypercalcemia are:
• Polyuria
• Polydipsia
• ‘Bones’ (bone pain and fractures
• ‘Stones’ (renal calculi)
• ‘Groans’ (abdominal pain, vomiting and constipation)
• ‘Moans’ (depression or confusion)
what is the treatment of hypercalcaemia?
Treatment is of the underlying cause, with fluids for rehydration and bisphosphonates
what are the causes of hypercalcaemia?
- Primary hyperparathyroidism
- Sudden acidosis, resulting in the releasee of bound calcium, which becomes ionized Ca2+
- Increased intestinal absorption due to excess
vitamin D or ingestion of calcium - Bone destruction resulting in increased Ca2+ release from bone – usually caused by secondary deposits from malignancy or myeloma
- Granulomatous disease
- Drugs e.g. thiazides
- Tertiary hyperparathyroidism in CKD
- Hypermagnesemia
what are the causes of hypophosphataemia?
excessive loss of phosphate • Hyperparathyroidism • Reduced absorption from GI (alcohol and medications such as antacids) • Significantly reduced intake • Malnourished • Anorexia nervosa • Refeeding syndrome • Diabetic ketoacidosis – insulin given • Respiratory alkalosis
how does respiratory alkalosis cause hypophosphataemia?
decrease in carbon dioxide as breathed out
pH in the cells becomes more alkaline as carbon dioxide leaves
stimulates glycolysis which requires a lot of phosphate
what is granulomatous disease
a congenital defect in the killing of phagocytosed bacteria by polymorphonuclear leukocytes, which cannot increase their oxygen metabolism due to dysfunctional NADPH oxidase. Causes formation of multiple granulomas
what are the signs of hypophosphataemia?
- ‘Stones’ – kidney and gallbladder
- ‘Thrones’ - polyuria
- ‘Bones’ – pain
- ‘Groans’ – constipation and muscle weakness
- ‘Psychiatric overtones’ – depressed mood and confusion
what is the treatment of hypophosphataemia?
Treatment involves oral or
intravenous phosphate and close monitoring of blood levels
what are the causes of hyperphosphataemia?
- Chronic kidney disease (↓GFR)
- Secondary hyperparathyroidism (kidneys unable to reabsorb Ca 2+)
- Pseudohypoparathyroidism (kidneys do not respond to PTH, genetic defect)
- Hypoparathyroidism
- Excessive intake (diet or phosphate based laxities)
- Cell death (crush syndrome, tumor lysis, rhabdomyolysis)
- Respiratory acidosis (low pH inhibits glycolysis so phosphate levels rise)
- Diabetic ketoacidosis
what are the signs and symptoms of hyperphosphataemia?
No symptoms with mild
hyperphosphatemia
Signs and symptoms of severe hyperphosphatemia include:
• Spontaneous firing of neurons
• Tetany
• Involuntary contraction of muscles
• Calcium phosphate crystal formation – kidney stones
what is the treatment of hyperphosphataemia?
Treatment is with phosphate binders (↓dietary intake) and forced diuresis ( IV saline and furosemide)
what influences an individuals normal GFR?
- Age
- Gender
- Size of individual
- Size of kidneys
- Pregnancy
what is a normal GFR for a baby at birth?
20ml/min/1.73m2
why is a babies GFR lower than an adults?
- Nephron development finished by 35th-36th week of fetal development (birth is usually at 38 weeks development)
- Premature and LBW infants often have lower nephron numbers
- Fetal excretion predominantly via placenta
- Normal GFR by ~ 18 months
how does advancing age in adults affect GFR
- GFR starts declining after 30 years of age
- Rate of decline = 6-7ml/min per decade
- Loss of functioning nephrons • Some compensatory hypertophy
how does age effect kidney size?
at 30-40 years there is some compensatory hypertrophy as there is loss of functioning nephrons
After about 50 the cortex volume drastically decreases and therefore so does the overall volume of the kidney even though the volume of the medulla increases.
how does pregnancy affect GFR?
- GFR increases (~ 50%)
• 130 – 180 ml / minute
• Kidney size increases (~ 1 cm due to Increased fluid volume)
• Nephron number the same
• Back to pre-pregnancy levels ~ 6 months post-partum
what causes decreased GFR?
decline in the number of nephrons
decline of GFR within individual nephrons
why might a decline in GFR not occur until significant damage to the kidney has occurred?
when kidney function declines slowly, individual nephrons can hypertrophy, maintaining GFR even though damage to the kidney is occurring. This compensation by individual nephrons will be overcome and GFR decline will therefore be noticeable once damage has occurred
what properties should a substance have for excretion rate to = GFR?
- Be produced at a constant rate
- Be freely filtered across the glomerulus
- Not be reabsorbed in the nephron
- Not be secreted into the nephron
what is inulin?
Inulin is a plant polysaccharide that is ingested into the body. It is freely filtered, not reabsorbed and not secreted and therefore can be used to estimate GFR
why do we not routinely use inulin to test GFR?
requires continuous IVI to maintain steady state
requires catheter and timed urine collections
other than inulin, what exogenous marker can be used to measure GFR?
51 chromium EDTA
- radioactive labelled marker
- cleared exclusively by renal filtration
what is the clinical use of 51 chromium EDTA?
to estimate GFR in children and where an indication of renal function is required such as in kidney transplantation
• Timed injection with blood samples taken 2,3,4 hours afterward
• Approx. 10% lower clearance than inulin (reabsorption?)
what is creatinine?
creatinine is the breakdown product of creatine and creatine phosphate in muscle
what factors affect the rate of production of creatinine?
muscle mass renal function (filtration and secretion) meat intake / diet
why is GFR over estimated when measured with creatinine?
As creatinine is secreted into the nephron, therefore levels measured in the urine over estimate the GFR as includes filtered and secreted creatinine. over estimates by 10 - 20 %
how is creatinine used to measure GFR?
- Urine Creatinine over 24 hours
* Serum Creatinine
what are the disadvantages of using creatinine to measure GFR?
- Cumbersome – (carrying a bottle of urine) & frequently inaccurate
- Overestimates GFR by 10 – 20% due to creatinine secretion (more with more severe renal impairment)
what is a normal serum creatinine level?
70 to 150 micromol/L
what factors increase serum creatinine levels?
- Large muscle bulk (Muscle cell breakdown)
- Young
- Male
- Black
- Creatine supplements
- High intake of meat
- Certain drugs e.g. trimethoprim
what factors reduce serum creatinine?
- Reduced muscle mass
- (Muscle cell breakdown)
- Old
- Female
- Hispanic / Indo-Asian
- Vegetarian
why is eGFR inaccurate in mild kidney disease?
• Reduction in GFR (e.g. if glomerular surface area reduced) causes increase in blood flow
• Reduced nephron number leads to nephron hypertrophy so no change in GFR
• Reduced filtration of creatinine (due to reduced GFR) results in increased
serum creatinine and increased secretion into the tubule (in order to maintain relatively steady state of serum creatinine)
