Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

MSC: Disease of major orgns > Calcium > Flashcards

Calcium Flashcards

1
Q

What are functions of Calcium?

A
  • Structure
  • Protection
  • Huge repository of calcium
  • Muscle function/contraction
  • Cell signalling
  • Blood coagulation cascade
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is involved in Calcium Homeostasis?

A
  • ​Achieved through interaction between calciotropic hormones and their effector tissues in the kidney, intestine and bone. Key to this is the calcium-PTH axis
  • Vitamin D and vitamin D receptors expressed within nucleus of parathyroid cells, play important role in calcium homeostasis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the forms of Calcium distributed through the body?

A
  • Calcium Hydroxyapatite
  • Calcium Phosphate
  • Intracellular Calcium
  • Plasma Calcium - bound calcium to Proteins and Anions, Ionised Calcium
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are reference ranges for calcium?

A
  • Ionised calcium = 1.13-1.32 mmol/L

​

  • Adjusted calcium = 2.20-2.60 mmol/L
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is Hypocalcaemia and Hypercalcaemia?

A
  • Hypocalcaemia = Adjusted calcium <2.20 mmol/L
  • Hypercalcaemia = Adjusted calcium >2.60 mmol/L
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the equation for Adjusted Calcium?

A

Measured [Ca] + (40 - [albumin]) x 0.02) = Adjusted [Ca]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are some drawbacks to Adjusted Calcium?

A
  • Relationship poor at extremes of relationship
  • Population specific – based on ‘healthy’ population
  • ?Use in ITU – ionised more useful.
  • Ionised calcium clinically more useful but impractical
  • Method specific – BCP/BCG (albumin); calcium (NM-BAPTA/AZ-III/CPC)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Where is Parathyroid Hormone secreted from?

A
  • PTH is synthesised, stored and secreted by chief cells which are in parathyroid glands.
  • Concentration of PTH in plasma determined by its synthesis and secretion by parathyroid glands
  • Magnesium is essential for secretion of PTH parathyroid gland
  • PTH acts directly on bone and kidney
  • Indirectly on intestine to regulate [Ca2+] and [PO4]
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Which organs metabolise and clear PTH?

A

Metabolism and clearance determined by liver and kidneys

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Which are features of the calcium sensing receptors?

A
  • G-protein coupled receptor
  • Expressed in parathyroid and renal tubules of kidney
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Which intracellular signalling pathways are triggered by Calcium Sensing Receptors?

A

There are 2 major pathways depending on the ionised [calcium]

  • Hypo – AC/cAMP pathway
  • Hyper – PLC/IP3/DAG pathway
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe the process of calcium regulation from detection by the calcium sensing receptor?

A
  • CaSR in the parathyroids detects reductions in extracellular Ca2+ and leads to the release of PTH
  • PTH acts on the PTH1 receptor (PTH1R) to increase resorption of Ca2+ from bone, promote urinary Ca2+ reabsorption and increase expression of the renal 1-α-hydroxylase (1αOHase) enzyme, which converts the 25-hydroxyvitamin D (25D) precursor metabolite to biologically active 1,25-dihydroxyvitamin D (1,25(OH)2D).
  • The elevated levels of 1,25(OH)2D increase absorption of dietary calcium by acting on the intestinal vitamin D receptor (VDR).
  • CaSR in the renal cortical thick ascending limb also acts independently of PTH to regulate urinary Ca2+ reabsorption
  • Increases in Ca2+ and 1,25(OH)2D concentrations lead to negative feedback on the parathyroid glands, thereby inhibiting further PTH release.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How is Calcium transported through the body?

A
  • Calbindin-D is vital in transport of calcium from lumen to lamina propria (ileum and duodenum are main sights for absorption)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Where is the Calcium Sensing Receptor expressed in the kidneys?

A

CaSR is expressed in the following portions of the nephron:

  • Apical membrane of the proximal tubule (60-70 % Ca2+ reabsorbed here), where it regulates 1,25(OH)2D synthesis and inorganic phosphate (Pi) excretion
  • Basolateral membrane of the cortical thick ascending limb of the loop of Henle
  • Apical membrane of the distal convoluted tubule, where it regulates Ca2+ reabsorption
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the action of Calcium Sensing Receptor in the mammary glands?

A
  • CaSR in the mammary gland detects reductions in Ca2+, which leads to increased PTH-related peptide (PTHrP) secretion from mammary epithelial cells into the circulation.
  • PTHrP acts on the PTH1R to increase bone resorption, which in turn releases Ca2+ for milk production.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the parathyroid hormone actions?

A

Bone

  • Osteolysis
  • Differentiation of osteoclasts
  • Regulation of osteoblasts (bone remodelling)
  • Bone resorption or formation (depends on duration of exposure and concentration

Kidneys

  • Reabsorption of Ca2+
  • Inhibition of phosphate reabsorption
  • Hydroxylation of 25(OH) vitamin D
  • Bicarbonate excretion (inhibits Na+-H+ anti-porter activity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How can PTH Mobilisation be described?

A

PTH mobilisation of calcium is biphasic

  • A rapid phase involving existing cells
  • Long term response dependent on proliferation of osteoclasts
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What happens to Serum and Urinary Calcium in the event of increased PTH?

A
  • Increase in serum total and free calcium
  • Urinary calcium is increased when larger filtered load of calcium from bone resorption and intestinal reabsorption overrides increased tubular reabsorption of calcium
  • In absence of disease the increase in serum calcium reduces PTH secretion through negative feedback loop maintaining homeostasis.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is PTH related peptide?

A
  • Synthesized in various tissues including keratinocytes, lactating mammary tissue, placenta and foetal parathyroid glands
  • Actions similar to PTH and binds to PTH receptors
  • Important in regulating Ca2+ fluxes between foetal and maternal circulations, Ca2+ concentrations in breast milk and a role in foetal development
  • Tumour marker
  • RR <1.8 pmol/L
20
Q

How does PTHrP differ to PTH?

A
  • PTHrp does not increase renal 1α-hydroxylase enzyme activity
21
Q

What is Calcitonin?

A
  • Produced by parafollicular C-cells of thyroid gland. It is a 32 amino acid peptide
  • Inhibits bone resorption by acting on the osteoclast
  • Not significant in the regulation of normal calcium homeostasis
22
Q

What can Calcitonin be used for in management?

A

Its potent anti-resorptive effect has led to its use in treating

  • Paget’s bone disease
  • Osteoporosis
  • Hypercalcaemia
  • Osteogenesis imperfecta
23
Q

What can lead to deviations in Calcium Homeostasis?

A

Hypercalcaemia

  • Increased GI absorption
  • Increased bone resorption
  • Decreased bone mineralisation
  • Decreased urinary excretion

Hypocalcaemia

  • Decreased GI absorption
  • Decreased bone resorption
  • Increased bone mineralisation
  • Increased urinary excretion
24
Q

What are reference ranges for Hypocalcaemia?

A
  • Mild adjusted calcium: >2.0-<2.2 mmol/L
  • Moderate adjusted calcium: 1.8-2.0 mmol/L
  • Severe adjusted calcium: <1.80 mmol/L
25
Q

What are causes of Hypocalcaemia?

A
  • Hypothyroidism: Magnesium deficiency, Post-surgical damage or neck irradiation, Infiltrative (e.g haemachromatosis,wilson’s disease and metastases), Genetic (DiGeorge syndrome)
  • Parathyroid hormone resistance: Pseudohypoparathyroidism
  • Abnormalities of vitamin D metabolism: Vitamin D deficiency
  • Deficient A1-hydroxylase enzyme activity: Chronic Kindey disease, Acidosis, Vitamin D-dependant rickets type 1
  • Vitamin D resisitance: Vitamin D-dependant rickets type 1
  • Others: Spurios, Acute Pancreatitis, Sepsis, Blood trnasfusion, Rhabdomyolysis, Bisphosphonate therapy, Hungry bone syndrome
26
Q

How does CKD affect calcium metabolism?

A
  • Fall in calcium: Decreased conversion 25(OH)D to 1,25(OH)2D
  • Increase in phosphate: Kidneys not excreting excess. FGF-23 has role in monitoring phsopahate
  • Increase in PTH: Stimulated by low calcium. Continual stimulation of parathyroid glands leads to secondary hyperparathyroidism
  • Patients with end stage renal failure can become hypercalcaemic. Probably due to development of autonomous PTH secretion from prolonged hypocalcaemic stimulus
  • Such hypercalcaemia may manifest for the first time in a renal transplant patient who becomes able to metabolise vitamin D normally leading to Tertiary hyperparathyroidism
27
Q

What is Pseudohypoparathyroidism (PHP)?

A
  • Resistance to PTH and various other glycoprotein hormones.
  • PTH resistance at the kidney so patients so hyperparathyroid bone disease
28
Q

What is Ellsworth-Howard test?

A

Involves measurement of serum and urinary phosphate and cAMP after intravenous administration of parathyroid extract; used in the diagnosis of pseudohypoparathyroidism. 6-30min urine collections and corresponding serum samples

  • Normally 10-12 fold increase in cAMP, fall in TmP/GFR of 20%
  • Pseudo type I: <5-fold increase in cAMP, <10% fall in TmP/GFR
  • Pseudo type II: normal response to cAMP, <10% fall in TmP/GFR
29
Q

What are symptoms of Hypocalcaemia?

A
  • Paraesthesia
  • Circumoral numbness
  • Cramps
  • Anxiety
  • Tetany are followed by convulsions
  • Laryngeal stridor
  • Dystonia
  • Psychosis
30
Q

What are clinical signs of Hypocalcaemia?

A
  • Chvostek’s sign: Gentle tapping over the facial nerve causes twitching of the ipsilateral facial muscles
  • Trousseau’s sign: Inflation of the sphygmomanometer cuff above systolic pressure for 3 minutes induces tetanic spasm of the fingers and wrist
31
Q

What are ECG changes of Hypocalcaemia?

A
  • Prolongation of the QT-interval
  • Narrowing of the QRS complex
  • Reduced PR interval
  • T wave flattening and inversion
  • Prominent U-wave
32
Q

How is Hypocalcaemia treated?

A

Treat underlying condition

  • Acute symptomatic patient (10-20 mL 10 % calcium gluconate over 5 mins, Follow with continuous infusion of 9-18mmol/2L/24 h)
  • Magnesium replacement
  • Cholecalciferol (Vitamin D3)
  • Alfacalcidol (1-α hydroxylated vitamin D3) - Given when 1-αhydroxylation defective (1-4 µg/day) e.g. hypoparathyroidism, VDDR I
  • Calcitriol (1,25(OH)2 vitamin D3) - 0.75-2.25 µg/day
33
Q

What are reference ranges for Hypercalcaemia?

A
  • Mild adjusted calcium >2.60-<3.0 mmol/L
  • Moderate adjusted calcium 3.0-3.5 mmol/L
  • Severe adjusted calcium >3.5 mmol/L
34
Q

What are causes of Hypercalcaemia?

A
  • Parathyroid hormone mediated: Sporadic (adenoma, hyperplasia or carcinoma) , familial , Ectopic parathyroid hormone in malignancy, tertiary hyperparathyroidism
  • Malignancy: Humoral hypercalcaemia of malignancy, Local osteolysis, Ectopic parathyroid hormone in maignancy, calcitriol related hypercalcaemia
  • Vitamin D related: Granulomatous disease, Vitamin D intoxication
  • Endocrine Disorders: Thyrotoxicosis, Adrenal insufficiency, Pheochromacytoma, VIPoma (Verner-Morison) syndrome
  • Drugs: Thiazide diuretics, Lithium, Milk-Alkali syndrome, Vitmain A, Parathyroid Hormone
  • Others: Coexisting malignancy and primary hyperparathyroidism, immobilisation, Acute renal failure, Chronic renal failure treaed with calcium and calcitriol or vitamin D analogues, Renal Transplant
35
Q

What are types of Hyperparathyroidism?

A
  • Primary: One or more parathyroid glands secrete excess parathyroid hormone
  • Secondary: Increased secretion of this hormone is a response to lowered ionised calcium as a result of kidney, liver, or bowel disease
  • Tertiary: State of autonomous secretion of parathyroid hormone usually occurs as a result of longstanding chronic kidney disease
36
Q

What is Primary Hyperparathyroidism?

A

One or more of the four parathyroid glands secrete excess PTH, resulting in hypercalcaemia

  • Parathyroid gland adenoma
    • 1 gland: 80 %
    • 2-3 glands: 10-11 %
    • ≥4 glands <10 %
  • Parathyroid carcinoma is rare (~1 %).
37
Q

What are typical biochemical features of Primary Hyperparathyroidism?

A
  • Increased PTH
  • Long Hx of moderate hypercalcaemia
  • Development of nephrolithiasis
  • Plasma PO4 low in 50% cases
  • Hyperchloraemic metabolic acidosis
  • Normal ALP seen in 50% of cases

Need to confirm Dx with clinical and radiological evidence

38
Q

What are indications for parathyroid surgery in PHPT?

A
  • Serum calcium 0.24 mmol/L above the upper limit of the normal range, for patients younger than 50 years of age
  • Men and peri-menopausal or postmenopausal women ≥50 years of age who have T scores of −2.5 or lower at a central bone densitometry site or in the distal third of the radius or who recently have had a fragility fracture
  • GFR <60 mL/min/1.73 m2
  • Renal stones, and a urine calcium level of >400 mg per day (10.0 mmol per day)
39
Q

What causes Hypercalcaemia in Malignancy?

A
  • Erosion of bone by secondaries
  • Production of PTH like substance e.g. PTHrP
  • Prostaglandin produced by tumour
  • Production of osteoclast activating factor
  • Coincidence of hyperparathyroidism
  • Ectopic PTH
40
Q

What is Familial Hypocalciuric Hypercalcaemia?

A
  • Autosomal dominant
  • Patients are heterozygous for inactivating mutations in the calcium sensing receptor (CaSR)
  • Set point for PTH increased, mild PTH dependent hypercalcaemia develops with hypocalciuria
  • In FHH inappropriate avid reabsorption of Ca2+
  • Largely asymptomatic (accounts for 2 %)
41
Q

What are symptoms and signs of FHH?

A
  • Lethargy
  • Polydipsia
  • Pancreatitis

Neonates with two mutations present with severe life threatening hypercalcaemia

42
Q

How is FHH differentiated from PHP?

A

UCa/Cr Cl ratio = (U[Ca] (mmol/L) x P[Creat] (µmol/L) / (P[Ca] (mmol/L) x U[Creat] (mmol/L)

Ca/Cr Cl ratio:

  • <0.01 in FHH
  • >0.015 in PHP
43
Q

What are signs and symptoms of Hypercalcaemia?

A
  • Tiredness
  • Malaise
  • Dehydration
  • Depression
  • Renal colic from stones
  • Polyuria or nocturia
  • Haematuria
  • Hypertension occurs
  • May have bone pain. Hyperparathyroidism mainly affects cortical bone
  • Bone cysts and locally destructive ‘brown tumours’ occur but only in advanced disease
  • Bone disease may be more apparent when there is coexisting vitamin D deficiency
  • Abdominal pain
  • Chondrocalcinosis and ectopic calcification (rare)
  • Corneal calcification (long-standing hypercalcaemia)
44
Q

What are ECG changes in Hypercalcaemia?

A

Hypercalcaemia speeds up repolarisation

  • Mild: Broad based tall peaking T waves
  • Severe: Extremely wide QRS, Low R wave, Disappearance of p waves, Tall peaking T waves.
45
Q

What is the treatment of Hypercalcaemia?

A

Mandatory if the patient is seriously ill or if Ca2+ >3.0 mmol/L

  • Rehydrate 4-6 L of 0.9 % saline on day 1, and 3-4 L for several days thereafter
  • IV bisphosphonates: Treatment of choice in malignancy and of undiagnosed cause. Zolendronate (4 mg) in 0.9 % saline and Pamidronate (60-90 mg) in 0.9 % saline
  • Prednisolone (30-60 mg daily): Used in granulomatous disease
  • Calcitonin (200 units i.v. 6-hourly, maximum use 5 days): Has short-lived action
46
Q

What are requirements for patients before the use of Bisphosphonates?

A
  • Ensure eGFR >60 mL/min/1.73 m2
  • [Ca2+] fall after 24-72 hours, lasting for approximately two weeks
47
Q

What are imaging techniques for Hypercalcaemia?

A
  • Abdominal X-rays may show renal calculi or nephrocalcinosis
  • High-definition hand X-rays can show sub-periosteal erosions in the middle or terminal phalanges
  • DEXA bone density scan is useful to detect bone effects in asymptomatic patients with HPT in whom conservative management is planned
  • USS which, though insensitive for small tumours, is simple and safe
  • High-resolution CT scan or MRI (more sensitive)
  • Radioisotope scanning using technetium (99mTc)sestamibi: 90 % sensitive in detecting adenomas

MSC: Disease of major orgns (23 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions