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Chemistry year 2 > Week 10 > Flashcards

Week 10 Flashcards

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1
Q

Bones have what

types of muscle

A

-dense outer layer and inner spongy layer

-skeletal (voluntary) , cardiac and smooth

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2
Q

Osteoporosis
and symptoms

tests for clinical indications

diagnostic tests

A

decreased bone density = fragile bones
-in post menopausal women
-asym until fractures

clinical indications -bone mineral density tests

diagnostic tests - Ca and Po4 levels (assessing bone metabolism,
increased Ca = hyperparathyroidism
low Ca = osteomalacia
ALP, d25, Osteocalcin

Bone mineral density test - DXA - primary diagnostic tool = measures bone density with dual energy X ray , results are a T score
if you have less than -2.5 you have osteo

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3
Q

pagets and symptoms

clinical indications tests:

diagnostic tests

A

chronic diorder that disrupts normal bone remodeling = enlarged bones

bone pain, deformities fractures, can have hearing loss

clinical indications increased ALP

diagnostic tests - ALP marker of bone formation increased in Pagets , fractures and osteomalacia

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4
Q

Quality assurance about serum testing

and DXA

A

serum processed quickly otherwise there will be changes in the CA due to prolonged storage
-hemolysis can falsely increase Ca

DXA-calibrate regularly , proper training to avoid errors in measurement

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5
Q

Muscular dystrophies

symptoms

tests for clinical indications

diagnostic tests

A

genetic disorder that causes progressive muscle weakness and degeneration

symp- muscle wasting , hard to walk , breathing problems

clinical indication - genetic testing, CK level

diagnostic test : CK released when there is muscle damage, increased in muscular dys and myositis
genetic testing to look for mutations like dystrophin in Duchenne Muscular Dystrophy

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6
Q

Quality assurance with
CK
Genetic Testing

A

CK - hemolysis falsely elevates CK

Genetic testing - avoid false neg/pos- contamination control and validation of sequencing techniques

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6
Q

myositis

symptoms

tests for clinical indications

diagnostic tests

A
  • muscle inflammation - autoimmune or infectious

symp - muscle pain, weakness,

clinical indicators - muscle biopsy, EMG, serum markers like CK and Aldolase

Diagnostic CK released when there is muscle damage, increased in muscular dys and myositis

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7
Q

Osteoarthritis

symptoms

tests for clinical indications

diagnostic tests

A

degenerative joint disease- cartilage and bone breakdown

Symp - joint pain, stiffness, especially if you havent been moving alot , reduced flexibility

Clinical indications- synovial fluid analysis , X rays

Diagnostic test-
synovial fluid - looks at viscosity, cell count, crystals diff between arthritis

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8
Q

Rheumatoid Factor

symptoms

tests for clinical indications

diagnostic tests

A
  • autoimmune disorder causing chronic inflammation of joints

Symps- swollen, warm, tender morning stiffness that lasts more than 30 mins, systemic symptoms like fatigue

Clinical indications- RF, ACPA- anti-citrullinated protein antibody, ESR

Diagnostic - presence of autoAB supports diagnosis but is not specific

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9
Q

Quality assurance of RF testing and Synovial fluid testing

A

RF testing - variability means this test needs standardized materials and regular calibration

Syno Flui - needs proper handling to avoid degradation especially for crystals

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10
Q

Tendinitis

symptoms

tests for clinical indications

diagnostic tests

A

inflammation of the tendon due to overuse or injury

symp - pain at tendon especially when moving - swelling

clinical indication - imaging to assess soft tissue involvement , lab tests to rule out infection or systemic

diagnostic
Imaging for soft tissues evaluation
MRI for soft tissue and bone

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11
Q

QA for imaging and lab tests

A

imaging - proper calibration
operator experience

lab tests - hemolysis and improper storage affect CRP and ESR

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12
Q

Bursitis

symptoms

tests for clinical indications

diagnostic tests

A

inflammation of the bursa (fluid fill sac that reduces friction between tissue)

symps - pain, swelling, limited movement of affected area

clinical indication - imaging to assess soft tissue involvement , lab tests to rule out infection or systemic

diagnostic
Imaging for soft tissues evaluation
MRI for soft tissue and bone

CRP/ESR increased in inflammatory bursitis - especially if infection or systemic disease suspected

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13
Q

Osteomalacia

symptoms

tests for clinical indications

diagnostic tests

A

issue with bone mineralization that causes bone softening due to Vit D deficiency

symp- bone pain, muscle weakness, increased risk of fracture

clinical indications-look at CA, PO4, VD, PTH

Diagnostic - D25 deficiency if < 50nmol/L
PTH - increased in 2ndary hyperparathyroidism as seen in VD def
CA- LOW or normal
ALP - increased
Xrays good to show pseudofractures (zones of decalification)

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14
Q

Rickets

symptoms

tests for clinical indications

diagnostic tests

A

softening of bones with Vitd def but in children causing bone deformities

symps - delayed growth, spine pain, skeletal deformities (bow leg, deformed spine and pigeon chest, dental issues”

clinical indications-look at CA, PO4, VD, PTH

Diagnostic - (Vit D) D25 deficiency if < 50nmol/L
PTH - increased in 2ndary hyperparathyroidism as seen in VD def
CA- LOW or normal
ALP - increased

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15
Q

how does osteoporosis occur

A

when bone resorption by osteoclasts is faster then bone formation by osteoblasts = decreased bone density

found mostly in post menopausal women due to decreased estrogen which impacts bone remodeling

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16
Q

risk factors to osteoporosis

A

major - over age of 65, history of fractures, use of glucocorticods, issues with nutrient absorption , early menopause

minor - smoking , low body weight , loss of height , kyphosis,
people are unware they have osteo until a fracture happens
rheumatoid arthritis and hyperthyroidism.

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17
Q

how to treat osteo

A

ca and Vd supplements
hormone replacement
biphosphonates
teriparatide

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18
Q

How does Vit D deficiency impact CA and PO4

A

vitamin D deficiency impairs calcium and phosphate absorption from the intestines, resulting in increased PTH levels, which causes bone resorption and the release of calcium from bones

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19
Q

Causes and risk factors from Vit D deficiency

A
  • inadequate sun exposure , dietary restrictions, obesity, impaired nutrient uptake

-GI diseases, liver diseases, and inherited conditions can also lead to osteomalacia and rickets by affecting the metabolism of vitamin D and phosphate.

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20
Q

how to treat rickets and osteomalacia

A
  • correct underlying def
    -Vit D and Ca supplements with increased sun exposure
    -PO4 supplements and analgesics
21
Q

CAI

PURPOSE

Specimen type

methodology

A

1 -3 mmol/L
-preferred for neonates
Purpose - free form of CA in blood needed for muscle contraction , nerve function and clotting CAI is 50% of Total Ca in blood

Hyper - hyperPTH, malignancy or Vit D toxicity
Hypo-hypoPTH, renal failure, Vit D def

Whole blood preferred - in heparinized syringe maintain anaerobic conditions
Plasma/serum- must be done quick to avoid pH changes (if pH decreases so does CAI)
-transport on crushed ice- inhibits glycolysis
-analyze in 30 mins

ISE- direct measurement - potentiometric

22
Q

Quality issues when testing for CAI

A

pH sensitivity - CAI is pH dependent
Alkalosis falsely lowers while acidosis increases
minimal air exposure

Pre ana errors - delays can cause inaccurate results
look at asap or keep anaerobic at stable temp

23
Q

CA

PURPOSE

Specimen type

methodology

A

2-3mmol/L- stored and released by sarcoplasmic reticulum

Total Ca includes ionzied and bound forms of CA- looks at overall CA status but not reflective of active status especially if you have altered protein binding

Hyper (twitching, tetany) /Hypo (depressive- slug) - like CAI for screening and followup of abnormal CA levels

Serum or Plasma- preferred
collect with EDTA FREE tubes so the anticoagulant doesnt chelate CA

Colorimetric assay - OCPC or arsenazo II dye binding method Abs change is proportional to concentration

24
Q

Quality issues with measuring Ca

A

Protein binding -
Total Ca can be affected by ALB, so if there is hypoALB you need to correct the CA

Anticoagulant interference - EDTA and citrate can chelate CA which can cause falsely low results

25
Q

MG

PURPOSE

Specimen type

methodology

A

0.6.-1
-levels in serum/plasma not specific
to one body system

-needed for enzyme function , neuromuscular activity and ca regulation from Scar retic , helps with metabolic processes

hypo- caused by malnutrition, chronic alcoholism and prolonged diuretic therapy , tetany, MI, renal loss, decreased gut absorption

hyper - seen in renal failure, excessive MG uptake or therapeutic use in preclampsia, found in antacids

serum or plasma - serum preferred
hemolysis will falsely increase

colorimetric assay - xylidyl ble and calmagite dye binding are used (total MG)

ISE used for FREE MG

26
Q

Quality issues when measuring MG

A

Hemolysis - RBC have high MG so if hemolysis occurs it will falsely increase MG (intracellular like K)

ANTICOG - EDTA, cit, and Oxalate interfere with magnesium measurement - dont use

lipemia , jaundice interfere with reading

-acidify 24 hr urine container with HCL

27
Q

PO4

PURPOSE

Specimen type

methodology

A

<0.1% of total body po4 is in plasma
-diurnal variation highest in the AM, fluctuates with exercise
-energy production, bone mineralization , cellular function. Regulated by the kidneys, VitD and PTH

hypo- malnutrition, chronic alcoholism and inherited disorders
hyper- CKD, hypo PTH, or excessive PO4 intake

-PTH increases PO3 in urine and lowers PO4 in serum
-Ca and P are inversely related

Serum or plasma - serum is preferred can use plasma but avoid ANTICOG that can chelate PO4

Colorimetric - PO4 reacts with molybdate to form a complex spectrophotometrically. proportional relationship

28
Q

Quality issues when measuring PO4

A

Hemolysis - false increase in PO4 after release from RBC

Stability - analyze quickly

pH - reaction should be acidic

contamination - contamination from phosphate detergents ; use acid washed dishes

29
Q

Vit D or D25

PURPOSE

Specimen type

methodology

A

-needed for Ca and Po4 homeostasis= bone health , increases intestinal absorption of Ca and P
-D25 marker for Vit D status

Deficiency - can cause rickets in kids, osteomalacia in adults and increased risk of osteoporosis

Toxicity - rare but with too much supplementation - causes hyperCA

Serum preferred

immunoassays- competitive binding like chemilumin ,
LC-MS/MS is gold standard

30
Q

Quality issues with measure Vit D D25

A

Handling - stable as serum in RT for short time, must refrigerate for long term storage for accuracy

31
Q

PTH

PURPOSE

Specimen type

methodology

A

-secreted by chief cells
-produced in response to low Free CAI
-targets bone and kidney and gut (since it stimulates production of Vit D)

  • regulates Ca and PO4 in blood and influences bone metabolism needed to diagnose hyper/hypo PTH
    -stimulates Osteoclastic activity

primary Hyper- increased PTH and Ca
hypo-low PTH and low Ca

serum or plasma- collected and store cold to prevent degradation . EDTA is preferred

immunoassay like two site or sandwich are most common to detect intact PTH

32
Q

Quality issues with PTH

A

Stability - unstable at RT, can degrade quickly , immediate refrigeration and quick analysis

Cross - reactivity - PTH assays can cross react with PTH fragments = false increase
make sure you use specific assays for intact PTH

33
Q

ALP

PURPOSE

Specimen type

methodology

A

-class 3 hydrolase with group specificity
- enzyme in tissues , highest conc in liver, bones, kidney and bile duct. use to assess bone and liver diseases

Bone disorders - increased in osteoblastic activity like Pagets, fractures, osteomalacia

Liver disease - increased in cholestasis, biliary obstruction and liver cirrhosis

serum fasting to avoid post prandial increase in ALP

colorimeteric assay - hydrolysis of p nitrophenyl phosphate that produces yellow product that you measure with a spec. change is proportional to ALP activity

-2-3 times greater than RI in 3rd trimester
-kids have 1-4 times more than adults

34
Q

Quality issues with ALP measuring

A

Hemolysis - causes false ALP increase

temp - keep at RT and analyze with in 4 hours

pH controlled 10.3 very alkaline

kinetic or rate reaction

RI is age and sex dependent

35
Q

ALP isoenzymes

PURPOSE

Specimen type

methodology

A
  • differentiates the source of elevated ALP is it bone, liver, placental or intestinal
    -measures BAP - expressed by osteoblasts when they start making new bone

Increased ALP to determine if bone (pagets) or liver (cholestasis)

Serum preferred

electrophoresis and heat inactivation - ID based on they mobility and heat stability
-immunoassay SPECIFIC for BAP - not used for diagnosis only monitoring

36
Q

Quality issues when looking at ALP isoenzymes

A

Sample handling

improper handling and storage can alter isoenzyme patterns .

37
Q

Calcitonin

PURPOSE

Specimen type

methodology

A

produced by para follicular cells (c cells) or thyroid . helps with ca and bone metabolism by inhibiting osteoclast activity by lowering CA levels. Tumor marker for medullary thyroid carcinoma MTC (increased)

hypercalcemia - calcitonin can be used with other markers to cause this
Used as a therapeutic agent for pagets

hypo-renal disease, fatty soaps from pancreatitis

Serum preferred - analyze quickly or it degrades

chemiluminescence or radioimmunoassay
(RIA) used - very sensitive and specific

antagonist to PTH
decreases Ca

38
Q

Quality issues with Calcitonin

A

Assay interference - heterophilic AB, biotin can increase or decrease use blocking agents

Specimen stability - unstable in serum, keep cold or frozen and analyze quick to avoid degradation

reference range - vary with age, gender and lab method - use method specific RI and consider the above

39
Q

CK

PURPOSE

Specimen type

methodology

A

found in skeletal muscle , heat, brain . Produces energy by catalyzing the conversion of creatine and ATP to ADP

MI - severe increase CK, - CKMD - heart damage

Rhabdomyolysis - severe increase due to muscle breakdown

Muscular Dystrophy - severe increase inherited disorders like Duchenne DMD have chronic elevations because of ongoing degradation

Myositis and Polymyo - inflammatory muscle diseases - increase

hypothyroidism - mild or mod increased due to muscle involvement in hypothyroid myopathy

severe increase over 5000U/L
mild increase after little muscle injury

40
Q

Specimen type for CK and handling methodology

A

Serum - preferred - sst , clot and spin

Plasma - in heparinized tube but values may differ- need consistency

handling - analyze right away to prevent degradation can be refrigerated,
freeze thaw cycles can lead to loss of enzyme activity

enzymatic assay where CK catalyzes conversion of CKP and ADP to Cr and ATP with a 2ndry reaction that produces a change in ABs with NADH proportional to CK activity

41
Q

Quality issues with CK testing

A

hemolysis - false increase as intracellular CK is released

Stability - CK activity decreases over time
test quick or refrigerate

non specific enzyme reactions can give background ABs = inaccuracies . Validate all methods so no cross reactivity or interference

Physical activity before test - significant increase - tell pts not to exercise before test

use lab RI - as it varies with age and gender

42
Q

Osteoblasts

A

bone formation
make bone matrix
regulate Ca and P
differentiate into mature osteocytes (bone matrix)

43
Q

Osteoclasts

A

-break down bone: resorption
-proteolytic enzymes & HCl demineralize & degrade bone matrix
-important role in bone remodeling & mineral
homeostasis

44
Q

Bone Remodelling regulated by

A
  1. Metabolism of Ca, P & Mg (minerals)
  2. Hormones (PTH, Vitamin D, calcitonin, growth hormone, estrogen/osteoporosis)
  3. Enzymes (ALP)
  4. Cytokines: substance produced by one cell that effects function of another cell
  5. Genetics, diet, physical activity
45
Q

Effect of PTH on bone:

A

increased
bone resorption: release of Ca and P into blood

46
Q

Effect of PTH on kidney:

A

increased Ca reabsorption
decreased P reabsorption
increased 1,25(OH)2 Vitamin D

47
Q

Effect of 1,25(OH)2 Vitamin D on intestine:

A

increased calcium-binding protein synthesis
increased Ca absorption in intestine
increased P absorption in intestine

48
Q

how does Calcium need to be collected

A

without venous stasis (stopping of blood)
-if tourniquet stops TP falsely increases
-no clenching if fist
-lying down decreases CA

acidify urine container with 6 mol HCL for U24
store a few days at 4, plastic and glass can absorb Ca
critical if <2.10 or >2.10

-If ALB decreases so does CA
-hemolysis , jaundice, lipemia can falsely increase

urine mmol/d
serum mmol/L

49
Q

bone formation marker

A

osteocalcin
made by osteoblasts
increased in bone diseases with bone turnover
-measure in serum with immunoassay

50
Q

done resorption markers

A

made by osteoclasts
-measure cross linking metabolites based on where they appear in the bone cycle

-associated with maturation of a bone
-If anti-resorptive drug therapy is effective, markers should decline within several months

Chemistry year 2 (12 decks)

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