MI & Liver Enzymes

Remember - does the investigation rule out/in? Dx

MI Enzymes

CK
- rises 3-6hrs after event
- only 50% pts show rise > ULofN @ 4hrs
- CK rises by over 50% over 12 hrs

CK-MB
- rises earlier than CK
- 3% CK-MB in skeletal muscle
- rhabdomyolysis = raised absolute levels
- better test = CK-MB/CK

+
Sys + ECG
CK-MB to confirm CK

Troponin

Myofibrillar protein fr damaged cells
- subtypes inc trop-T/trop-I
Measured at 12hrs post onset
Elevation persistent up to 10 days
Can indicate low-grade myocardial damage before infarction, requiring acute treatment
Good specificity

Liver Enzymes

ALT - cytosolic enzyme

ALP - biliary brush border enzyme
GGT - ribosomal test, x liver specificity

Enzymes

Raised Levels
*most significant finding
- increased synthesis/cell proliferation
- cell membrane damage
- cell death
- defective/slow blood clearance
Level increased can = extent of injury
Isoenzyme = greater tiss specificity

Enzyme profiles

1) tissue of origin
2) isoenz pattern in tiss
3) timing in relation to disease
4) lab availability

Normal variations of enzyme levels

1) Age/sex variation in reference range (ALP higher in adolescents)
2) Race (CK higher in afro-Caribbean)
3) Analytical interference (transaminases & LDH - haemolysis from red cells)
4) Renal failure (Amylase increased, as excreted renal-ly)
5) 'Macro enzymes' - binding of enzyme to immunoglobulin - lowers rate of degradation
- primary protein (immunoglobulin) disease eg myeloma
- temp
- *CK & AMY
- = req alt of Ix w/ documentation

Dx

MI
CK & CK-MB
troponin (non-enzyme)

x transamimases/LDH

Liver
ALT
ALP
GGT

Pancreatitis
Amy

Skeletal

CK for muscles
ALP for bone

Osteoporosis

Reduction in bone mass via loss of matrix
Excessive bone loss
Normal mineral:matrix ratio

Causes
Old age (post-menopause)
Endocrine
 - premature ovarian failure (early menopause)
- Cushings
- thyrotoxicosis
Drugs
Steroids
Heparin

Ix
pl Bone profile = normal
DEXA
- Identify fast bone losers
- Monitor therapy (HRT, bisphosphonates)

Osteomalacia

...aka rickets in children

Defective mineralisation of bone (calcium deficiency) + Increased osteoid

Causes
Dietary/Malab - Ca/vit D def
x Exp to sunlight
Disordered vit D metabolism
- renal Dis (decreased 1-hydroxylation)
- vit D-dep rickets (1alpha-hydroxylase def)
- a-convulsive therapy (induces metabolism)
Low phosphate (Renal Tubular Leak)

Ix
low sCa & PO4
high ALP (osteoblastic response) - interpret with age-related ref range
low circulating 25-OH cholecalciferol (?diet def)
elev sPTH (2ry HPThm)

Hypocalcaemia

Hypocalcaemia

Sy & Si
MSK - numbness, parasthesia, muscle cramps, convulsions
+ve Chvostek's & Trousseau's signs

Bone - myopathy & bone pain (low vit D)

Eyes - cataracts (chronic)
Brain - behav disturbances

Ix

ECG = Prolonged QT

Causes (NB hypoalbuminaemia)
Low vit D
Disordered vit D metabolismm (eg Renal Failure)
hPTH (congenital, AI, post Thyroid Sx, infiltrations)
PseudohPTH (PTH resistance)
Mg depletion (impaired PTH synthesis/release)
Acute pancreatitis
Neonatal
Massive blood transfusion (citrated blood)
Artefactual ( Blood sample collected into EDTA/citrate)

hCa + low/undetectable PTH = hPTm

hCA+elevated PTH = non-PT causes (except pseudo hPT)

Hypercalcaemia

"Bones, Stones, Abdo Groans & Moans"

Si&Sy
GI - Anorexia, N&V, Abdo pain & Constipation, Peptic ulceration & Acute pancreatitis
Renal - Polyuria & polydipsia, calculi & nephrocalcinosis, renal failure
CVS - HTN, heart arrhythmias
MSK - weakness, lassitude
Eyes - corneal calcification
Mental changes
Underlying Disease

Causes
*
1ry HPTH (1/1000)
Malignancy (*myeloma)
- Bony mets
- Tumour - PTH related peptide
- Tumour - HCa agonists
Other
Sarcoidosis (increased calcitriol synth)
Vit D intox
3ry HPTH (eg CRF - post Tx)
Immobilisation (Paget's, Adolescents)
Thyrotoxicosis (severe)
Tz diuretics
Familial hypocalciuric HCa (v rare)

HCa + supp PTH = non-PTH Cause
HCa + raised/detectable PTH = PTH-mediated cause

Calcium Haemostasis

Haemostasis
Skeleton = 1kg/25000mmol/99% body Ca
Dietary Intake of Ca = 25mmol/day
Exchange between ECF and bone = 10mmol/day
*renal (imp in regulation)
GIT... also involved

Pathology
... occus with...
- Gut, renal, skeletal problems
- Parathyroid disorders
- Abnormal Vitamin D metabolism

Ix
*Total plasma calcium
plCa = alb-bound 40%, complexed 10%, free ionised fractions 50%
Ionised Ca = active fraction - roles in bone, teeth, neuromuscular activity, coagulation (enzyme co-factor)

Corrected Ca = Ca + 0.02(40-Albumin)


Parathyroid Hormone
Increase in PTH - stim by
 - low Ca
 - raised PO4 (Chronic effect only)
Only intact PTH is active
...act on...
Kidneys
 - incrs Ca reabsorption
 - decrs PO4 reabsorption
 - decrs HCO3 reabsorption
 - incrs 1-alpha-hydroxylation of vit D (activated)
Bone
 - incrs osteolclastic resorption


Vit D
Dermal synthesis & Diet
Liver = 25-OH cholecalciferol - 'inactive'
Renal = 1,25 dihydroxycholecalciferol (calcitriol - 'active')
Calcitriol stim by...
- low ionised Ca (via PTH)
- low PO4
- low vit D
Calcitriol acts on...
- gut = incrs Ca & PO4 absorption
- renal = incrs Ca & PO4 reabsorption
- bone - incrs resorption/mineralisation, remodelling


Calcitonin (Thyroid 'C' Cells)
hCa actions
- stim by increased Ca ions