Hyprecalcaemia and hypocalcaemia disorders Flashcards
1
Q
How is calcium controlled?
A
- PTH
- metabolites of vitamin d
- calcitonin
2
Q
How does PTH increase Ca?
A
- KIDNEY:
- BONE
- GIT
- increases urine phosphate excretion (phosphaturia)
3
Q
Actions of calcitriol
A
Papp
4
Q
Why is calcium important?
A
Nn conduction and Neuromuscular transmission
- muscle contraction
- intracellular messenger involved in any number of cell signalling pathways
- coagulation
- vital maintenance of cell membrane integrity
- second messenger roles
5
Q
Why is calcium important
A
- nn conduction and NM transmission
- mm contraction
- intracellular messenger involved in any number of cell signalling pathways
- coagulation
- intracellular Ca maintained at v low levels: vital for maintenance of cell membrane integrity, second messenger roles
6
Q
How is Ca distributed in the body?
A
- 2 main pools: bone and ECF
- almost all calcium in bone is present as calcium hydroxyapatite (very poorly exchangeable)
- EC calcium is biologically measurable form, includes: Ca bound to albumin, Ca chelated to various compounds, Ca free in solution or ‘ionised calcium’
7
Q
Describe Ca uptake in GIT
A
active
8
Q
How is Ca stored in bones?
A
Ca mobilised by osteoclasts with Ca and phosphate being released
9
Q
Is calcium phosphate soluble or insoluble?
A
insoluble (calcium and phosphate are excreted separately by kidneys)
10
Q
Control of Ca
A
- PTH
- metabolites of vitamin D (1,25 dihydroxycholecalfierol most active)
- calcitonin
11
Q
Outline PTH action
A
- INCRASES CA at KIDNEY: increases Ca resorpton, promoting conversion of 25 D3 to 1.25 D3
- INCREASES CA at bones: activation of osteoclast activity
- INCREASES Ca at GIT: enhanced Ca resorption from gut, mainly mediated through 1,25 D3
- INCREASES urinary phosphate excretion
12
Q
Actions - calcitriol
A
- increases serum Ca through number of mechanisms:
- increasing GIT absorption of calcium
- facilitating renal absorption of calcium
- by mobilising Ca and PO4 ffrom bone
- calcitriol has negative ffedback on its own secretion, inhibits PTH secretion
- maintains aspects of immune system
13
Q
What do PTH, metabolites of vit D and calcitonin respond to?
A
ionised Ca levels
14
Q
Total serum Ca level = ?
A
2.45-2.83 mmol/L
15
Q
Describe different calcium states
A
- ULTRAFILTERABLE CALCIUM: ionised and complexed forms
- Protein bound calcium (1/3, almost exclusively to albumin)
16
Q
How to measure serum Ca
A
- prinicipally interested in ionised calcium
- so always also look at albumin levles
17
Q
What artefacts are ionised calcium measurements prone to?
A
- any increase in pH increases protein binding and decreases ionised calcium
- increases in pH can occur through exposure to air, agitation, variation in [heparin]
- numerous devices can measure this ‘at bedside’
18
Q
T/F: as CaPO4 is insoluble, for the mobilisation of Ca from bone to result in an increase in ionised Ca, the PO4 has to be readily removed
A
True
19
Q
Outline disturbances in Ca balance
A
- needs to be significant disruption of hormonal control of Ca or the organs involved in absorption/storage/excretion of Ca
- results in hyper/hypocalcaemia
- or may result in altered bone metabolism without changes to serum calcium
20
Q
Which 2 hormones are principally involved in controlling clinically signifciant alterations in serum ca concentrations?
A
- PTH
- 1,25 D3 calcitriol
21
Q
Why do you need to look at the phosphate levels when looking into possible Ca disturbances?
A
it is the calcium phosphate product that is producing irreversible soft tissue calcification (
22
Q
When can hypercalcaemia be ignored?
A
never - repeatable hypercalcaemia should always be investigated, even in absence of obviou CS
23
Q
Result of prolonged untreated hypercalcaemia
A
(especially with normal or increased phosphate) an lead to irreversible damage to many organs especially kidneys.
24
Q
CS - hypercalcaemia
A
- PD and PU
- weakness, lethargy, depression
- inappetence, vomiting, diarrhoea, constipation
- facial pruritus and oral discomfort
- mm twitching and fasiculations
- cardiac tachydysrhythmias
- sudden death
- or no detectable CS at all!
25
Clinical pathology - hypercalcaemia
- hypercalcaemia
+/- disruption to serum phosphate concentration
- with or without evidence of disruption to renal function
26
Effect of hypercalcaemia on renal function
- hypercalcaemia interferes with tubular function so the animal has trouble concentrating its urine --> USG azotaemia
- structural renal disease if accompanied by elevated serum phosphate (CaPO4 product of >5-6)
27
Clinical pathology - hypercalcaemia
- hypercalcaemia
- with or without disruption to serum phosphate concentration
- with or without evidence of disruption to renal function characterised by azotaemia and IDU (inappropriately dilute urine)
- impaired renal function can result in alterations to calcium and phosphate metabolsim (hyperphosphataemia and non-ionised hypercalcaemia)
28
Causes - hypercalcaemia
- non-pathological reasons (rapidly growing young dogs, lab error)
- transient or interpretive (haemoconcentration, hyperalbuminaemia)
- pathological (d/t increased PTH or PTH-like activity, unrelated to increased PTH activity)
29
Outline pathological causes of hypercalcaemia
- INCREASED PTH ACTIVITY: primary hyperparathyroidism
- INCREASED PTH-LIKE ACTIVITY: humoral hypercalcaemia of malignancy, lymphosarcoma, anal sac adenocarcinomas, multiple myelomas etc etc
- UNRELATED INCREASED PTH or PTH1a: non-parathyroid hormone dependent causes of hypercalcaemia
30
Outline increased PTH and PTH-like activity
- ionised hypercalcaemia and low or non-elevated phosphate are typically present
- serum PTH likely to be 'inappropriately not suppressed' or there may be an elevation in serum PTHrP or some other PTH-like compound
- PTHrP is measurable, others are not:
31
Causes of hypercalcaemia not related to PTH-ish activity
- vitamin D toxicity (excessive supplementation, rodenticides, psoriasis creams)
- granulomatous inflammation
- hypoadrenocorticism
- CKD (grape intoxications)
- idiopathic (cats)
- significant osteolysis
32
Describe primary hyperparathyroidism
- keeshund markedly over-represented in developing primary hyperparathyroidism (autosomal dominat, with age-related penetrance)
- increased and autonomous PTH production by a functional neoplasm (usually solitary adenoma)
- disease of older dogs, generally over six years, uncommon in cats
- calcium negative feedback is lost
33
CS - primary hyperparathyroidism
- these dogs often well (hypercalcaemia may be incidental)
- often unremarkable PE
- may develop urolithiasis and then show LUT signs - dysuria, pollakiuria, haematuria
- uncommon for other signs of hypercalcaemia
34
Outline hypercalcaemia of chronic renal disease
- most animals with azotaemic CKD will have serum calcium in the reference range
- 14% of dogs and 38% cats are hypercalcaemic and it will be an ionised hypercalcaemia in 10% dogs, 28% cats
- hyperphosphataemia will also be present
- NOT secondary to renal hyperparathyroidism (all these patients have NORMAL Ca)
35
Outline idiopathic hypercalcaemia
- perhaps commonest cause of hypercalcaemia in cats
- as idiopathic, is a diagnosis of exclusion
- generally middle-aged cats
- commonly develop Ca oxalate uroliths throughout urinary tract
- monitor Ca, USG, renal function
- management: try dietary and then other management
36
Outline management of hypercalcaemia
- correct underlying cause or causes
- consider tx to reduce the degree of hypercalcaemia: fluid therapy, furosemide, bisphosphonates (pamidronate or alendronate)
37
Outline management of hypocalcaemia
- not uncommon as clinically insignificant result of hypoalbuminaemia
- BUT ionised hypocalcaemia is most frequently (dogs 3-%, cats 50%) associated CRF and:
- pancreatitis
- primary hypoparathyroidism
- iatrogenic hypoparathyroidism
- eclampsia
38
CS - hypocalcaemia
- abnormal neuro, neuromuscular and GIT function or combinations of all these:
- panting, anxiety and behavioural changes
- weakness with a stiff and stilted gait
- inappetance through to vomiting
- hyperthermia
- mm tremors and cramps, mm pains
39
Management - hypocalcaemia
- once you have determined the hypocalcaemia is clinically significant and have corrected a potential underlying cause then:
- acute IV 10% calcium gluconate
- subacutely oral medication
40
What does hypercalcaemia in cats seem to be caused by?
- CKD
- 'idiopathic' hypercalcaemia
- rest
41
What doses hypercalcaemia in dogs seem to be caused by?
- neoplasia
- primary hyperparathyroidism
- the rest
42
Management - hypocalcaemia
- frequently an unimportant problem clinically as it can result of other abnormalities
- must be tx when cause of CS it absolutely needs managing it as life-threatening
- consequently whenever detected it should ALWAYS be investigated to level that makes you comfortable
