Lab Dx Exam 9 (Rheumatology and MSS Labs)

What is uric acid?

Nitrogenous compound and product of purine catabolism

Majority excreted by the kidneys

What are some causes of elevated uric acid?

- Overproduction or decreased excretion by the kidneys (e.g., renal failure)

- Foods high in purine (ex: red meats)

If uric acid is saturated in the urine, what can this cause?

crystals (body increases pH, uric acid is less saturated in alkaline --> prevents crystallization/stone formation)

What is the difference between hyperuricemia and uricosuria?

Hyperuricemia: elevated uric acid in serum (blood)

Uricosuria: elevated uric acid in the urine (has increased risk for kidney stones)

When do we check uric acid levels?

In patients with monoarticular arthritis

If the uric acid level is high and pt is susceptible, uric acid crystals will form in tissue and joints and provoke a severe inflammatory response

What is uric acid clinically associated with?

- gout, but not all gout pts have very high levels

- some pts with very high levels don't develop gout

What causes increased serum levels of uric acid?

- Gout

- Alcoholism

- Aspirin

- Caffeine

- Leukemia

- Metastatic cancer

- Multiple myeloma

- Renal failure

- Diuretic therapy (HCTZ)

- Idiopathic

What causes decreased serum levels of uric acid?

- Lead poisoning (not seen a lot, can be seen in children)

- Wilson disease

- ALS

What is Sjogren syndrome?

Autoimmune disease characterized by progressive destruction of the lacrimal and salivary glands, leading to mucosal and conjunctival dryness

Can occur by itself or in conjunction with other autoimmune disorders such as SLE, RA, scleroderma

What antibodies do we see in patients with Sjogren syndrome?

- Anti-SSA (anti-RO)

- Anti-SSB (anti-LA)

- Anti-SSC

These are all subtypes of antinuclear antibodies (ANAs)

What percentage of patients with Sjogren have either anti-SSA or anti-SSB antibodies?

- Anti-SSA --> ~70% of patients, can also be found in 25% of pts with SLE

- Anti-SSB --> 1/2 of pts with Sjogren, rarely present in pts with SLE

When do we usually see anti-SSC positive?

Positive in 75% of pts with RA or in pts with RA and secondary Sjogrens

What is scleroderma?

Multi-system autoimmune disorder that is characterized by inflammation with fibrosis of the small blood vessels in the skin, heart, lungs, kidneys, and GI tract (aka affects pretty much all organs)

What antibody do we commonly see in scleroderma?

Anti-scleroderma antibody (Scl-70 antibody) --> an antinuclear antibody

Used to dx scleroderma, found in 45% of pts with scleroderma

What is another name for scleroderma?

Progressive systemic sclerosis (PSS)

What is the anti-centromere antibody?

Present in ~57% of patients with limited scleroderma (previously called CREST syndrome)

Rarely found in patients with other connective tissue diseases or in healthy patients

What is CREST syndrome?

Limited cutaneous systemic sclerosis or limited scleroderma

Consists of:

- Calcinosis

- Raynauds

- Esophageal deformity

- Sclerodactyly

- Telangiectasias

What is osteoporosis?

Skeletal disorder characterized by compromised bone strength predisposing to an increased risk for fracture

Associated with thin and weak bones that are prone to fracture

What is a DEXA scan?

Bone densitometry, used to determine bone mineral content (BMC) and density (BMD)

Used to dx osteoporosis and osteopenia as well as monitor effectiveness of therapy

What does a DEXA scan evaluate?

- Lumbar spine (cancellous bone)

- Hip (mixed bone)

- Radius (cortical bone)

How often is a DEXA scan recommended to be repeated for screening and monitoring of osteoporosis?

Every 2 years

When does the USPSTF recommend screening for osteoporosis?

In women over 65 OR postmenopausal women younger than 65 at increased risk of osteoporosis

What is a T-score?

Compares the bone mineral density (BMD) of the pts results to a young healthy adult (30 years old)

Positive T score indicates normal BMD

Negative T score indicates reduced BMD

What are the different values of a T score and what do they correspond to?

Normal: T-score greater than -1

Osteopenia: T-score between -1 and -2.4

Osteoporosis: T-score equal to or less than -2.5

What is a Z-score?

Compares the patient's results to a group of age-matched controls --> looks at where the patient is compared to "normal"

Helps us look for any secondary issues that may be causing the osteoporosis/penia

A score of -2 or lower indicates a secondary cause

What is a fracture risk assessment (FRAX)?

Estimates 10 year fracture risk from femoral neck bone density and clinical risk factors

What are bone turnover markers (BTMs)?

Used to monitor osteoporosis, can identify significant improvement in a few months after starting therapy (within 3-6 months)

Used to determine effectiveness and compliance of tx comparing BTMs with pre-tx levels

What are the different types of BTMs?

- N-telopeptide

- C-telopeptide

- Amnia-terminal propertied of type 1 procollagen

- Osteocalcin

- Pyridium

What are N-telopeptide (NTx) and C-telopeptide (CTx)?

Protein fragments that are seen in the bloodstream and excreted in the urine when the bone breaks down

NTx used to monitor successful therapy

What do elevated levels of N-telopeptide (NTx) indicate?

An increase in bone resorption (breakdown)

Can be seen with: osteoporosis, Paget disease, bone tumors/metastasis, hyperparathyroidism

NTx levels decline with:

Effective use of treatment

A reduction of what percent or more of NTx after 6 months of treatment indicates a satisfactory response to therapy?

50% or more

What is granulomatosis with polyangiitis (Wegener's granulomatosis)?

Rare autoimmune disease associated with systemic vasculitis in which the small and medium arteries of the kidneys, lungs, and upper respiratory tract are damaged by a granulomatous inflammation

Definitive dx is made by biopsy of the affected tissues

What antibody is used to assist in the dx of Wegener's granulomatosis?

Antineutrophil cytoplasmic antibody (ANCAs, c-ANCA and p-ANCA)

What is antineutrophil cytoplasmic antibody?

Used to assist in dx of Wegener's granulomatosis

Tracks the course of the disease, monitors the response to therapy, provides early detection of relapse

What are the 2 major patterns of staining of anti-neutrophil cytoplasmic antibody?

- c-ANCA

- p-ANCA

What is cytoplasmic ANCA (c-ANCA)?

Coarse granular staining of the cytoplasm

Main antigen is proteinase-3 (PR3), seen in ~90% of WG

What is perinuclear ANCA (p-ANCA)?

Staining of the nucleus and perinuclear area, leaving cytoplasm clear

Main antigen is myeloperoxidase (MPO), seen in ~50% of WG but also seen in pts with IBD such as UC (50-70%) and Crohn's (20%)

What is multiple myeloma?

Malignancy that is part of a spectrum of diseases ranging from monoclonal gammopathy to plasma cell leukemia

What are presenting symptoms of multiple myeloma?

- Bone pain

- Pathologic fractures

- Weakness, Malaise

- Hypercalcemia

- Renal failure

- Neuropathies (numbness/tingling)

How do we diagnose multiple myeloma?

- 24-hour urine collection for quantification of the Bence Jones protein (i.e., lambda light chains)

- M-spike at the beta or gamma globulin zone in SPEP

What is serum protein electrophoresis (SPEP)?

Separates the various components of protein into bands or zones according to their electrical charge

Can demonstrate polyclonal or monoclonal spikes

What are polyclonal spikes on SPEP? Monoclonal spikes?

Polyclonal: associated with infectious or inflammatory disease

Monoclonal: often neoplastic

If a patient has a monoclonal spike (M-spike) in the beta or gamma globulin zone on SPEP, what does this indicate?

Associated with multiple myeloma

What is useful for determining the type of renal damage in a patient if present, when suspecting multiple myeloma?

Urine protein electrophoresis

What is Bence Jones protein?

Detected in urine using urine protein electrophoresis

Monoclonal light-chain portions of immunoglobulin found in 75% of patients with MM

What is creatine kinase (CK)?

Found predominantly in the heart muscle, skeletal muscle, and brain

Elevated during a muscle or nerve injury, rises within 6 hours after damage --> if damage is not persistent, will return to normal within 2-3 days

What is CK used to support the diagnosis of?

- Myocardial muscle injury (infarction)

- Neurologic disease

- Skeletal muscle disease

What are the different creatine kinase isoenzymes?

- CK-MB

- CK-BB

- CK-MM

What is CK-MB?

Rises with heart damage

Examples: MI, PE, CHF

What is CK-BB?

Found predominantly in the brain and lung injury

Examples: CVA and PE

What is CK-MM?

Rises with injury to or disease of the skeletal muscle

Examples: rhabdomyolysis, vigorous exercise, electroconvulsive therapy, crush injury, recent surgery

CK-MM varies on patient's muscle mass --> muscular patients may have elevated CK

CK-MM varies on:

Patient's muscle mass --> muscular patients may have elevated CK

What are the isoforms of CK-MM?

MM1 and MM3

Useful for detecting cardiac disease (heart attack)

MM3/MM1 ratio over 1 suggests:

Acute myocardial injury

What could cause increased levels of CK-MM isoenzymes?

- Rhabdomyolysis

- Muscular dystrophy

- Myositis

- Recent surgery

- Multiple IM injections

- Crush injuries

- Delirium tremors

- Recent convulsions

- Electroconvulsive therapy

- Shock

- Hypokalemia

- Hypothyroidism

- Trauma

What is aldolase?

Enzyme used in glycolysis

Used to aid in the dx and surveillance of skeletal muscle or hepatic disease

Very high levels of aldolase are seen in pts with:

- Muscular dystrophy

- Dermatomyositis

- Polymyositis

- Muscular trauma

Elevated levels (not super high) can also be seen in pts with chronic hepatitis and liver cirrhosis

What can cause increased levels of aldolase?

- Hepatocellular disease (ex. hepatitis)

- Muscular disease (ex. muscular dystrophy, dermatomyositis, polymyositis)

- Muscular trauma (ex. severe crush injury)

- Muscular infections (ex. trichinosis)

- Gangrenous processes (ex. gangrene of the bowel)

- MI

What can cause decreased levels of aldolase?

- Hereditary fructose intolerance

- Muscle-wasting disease (ex. ALS)

What are complement assays?

Screening test that is used to dx hereditary and acquired deficiencies

Looks at the complement system of inflammation to determine if there are any abnormalities

What is the complement system?

Part of the innate immune system

Plays a critical role in the defense against infections, promotes inflammatory response, eliminates pathogens, and enhances the immune response

What can complement assays monitor the activity of?

Infectious or autoimmune disease

EX. Hereditary angioedema, SLE, infectious endocarditis, vasculitis, glomerulonephritis

What are the different serum complements?

- group of 31 proteins that act as enzymes, cofactors, inhibitors

- labeled C1-C9 (diff dz are associated w/different complement deficiencies)

What is arthrocentesis?

Aspiration of fluid from a joint

Can also be used to deliver medications into a joint space (intra-articular injection)

What is arthrocentesis used for?

To rule out:

- Infection

- Arthritis

- Crystal-induced arthritis (gout vs. pseudogout)

- Synovitis

- Neoplasms of the joint

What is the technique for an arthrocentesis?

Insert sterile needle into joint space to obtain synovial fluid

What are the major joints within which we can do an arthrocentesis?

- Knee

- Shoulder

- Hip

- Elbow

- Wrist

- Ankle

Why is a hip arthrocentesis not usually done in the office?

Lots of blood vessels in the area, needs to be done with imaging

What should the normal color of synovial fluid be?

Clear, straw colored, no blood

If a patient's synovial fluid has low glucose, what can this indicate?

- Inflammation

- Septic arthritis

- RA

If a patient's synovial fluid has increased uric acid, what can this indicate?

Gout

If a patient's synovial fluid has increased protein and lactate levels, what can this indicate?

Bacterial infection, inflammation

If a patient's synovial fluid has high WBCs with neutrophils, what can this indicate?

Acute bacterial infection

If a patient's synovial fluid has high WBCs with lymphocytosis or monocytosis, what can this indicate?

Gout or RA

If a patient's synovial fluid has decreased complement (protein) levels, what can this indicate?

- SLE

- RA

- Other immunologic arthritis

If a patient's synovial fluid has cloudy color, what can this indicate?

Infection

If a patient's synovial fluid has low viscosity, what can this indicate?

Inflammation

What is a gram stain?

- Test to determine if a bacteria is gram + or gram -

- Can describe shape (rods, cocci, diplococci in clusters, etc.)

- Must be ordered in addition to arthrocentesis

If a patient's arthrocentesis gram stain comes back + for calcium crystals, what does this indicate?

Pseudogout

If a patient's arthrocentesis gram stain comes back + for cholesterol crystals, what does this indicate?

RA

If a gram stain is purple small spheres, what kind of bacteria is it?

Staphylococci (gram +)

If a gram stain shows needle shaped crystals, what does this indicate?

- Uric acid crystals

- Negative bifringement, GOUT

- Yellow when parallel to compensator ray

If a gram stain shows rhomboid shaped crystals, what does this indicate?

- Calcium crystals

- Positive bifringement, PSEUDOGOUT

- Blue when parallel to compensator ray

What are antinuclear antibodies (ANAs)?

Group of antinuclear antibodies used to diagnose SLE and other autoimmune diseases

Some of them are specific for SLE, some are associated with other rheumatological diagnoses (SLE, scleroderma, Sjogren's, CREST)

How many SLE patients have positive ANAs?

~95%

Since almost all patients with SLE develop ANAs, a negative ANA excludes the diagnosis

When should we check ANA levels?

In patients with high suspicion of autoimmune disease (ex. young pts complaining of fatigue, joint pain, rash, fever)

ANA titers less than 1:40 are:

Negative (not significant)

ANA titers more than 1:160 are:

Significantly positive

Low-level ANA titers can be seen in:

Elderly or some healthy people

Why do we need to order more tests if a patient's ANA results come back positive?

A lot of rheumatological disorders will have a positive ANA --> in order to determine which the patient has, need additional testing

How are titers expressed?

- in terms of the way in which they are made

- dilution 1 in 8 is made by mixing 1 volume of serum w/7 volumes of diluents (normal saline)

If you see an anti-centromere ANA pattern, what does this indicate?

PSS (CREST)

look at ANA pattersn slide

What is lupus?

- autoimmune dz that can damage any part of your body

- chronic, waxes and wanes

What are anti-DNA antibodies?

Used to diagnose lupus

2 kinds:

- Anti single stranded DNA (anti-ssDNA)

- Anti double stranded DNA (anti-dsDNA)

What is anti single stranded DNA (anti-ssDNA)?

Anti-DNA antibody that can indicate SLE

Less sensitive and specific --> not in clinical use

What is anti double stranded DNA (anti-dsDNA)?

Anti-DNA antibody that is 95% specific and 70% sensitive for SLE --> supports dx of SLE

Occasionally found in other conditions such as RA, drug-induced lupus, autoimmune hepatitis

Higher levels of anti-dsDNA is predictive of:

Renal problem (nephritis) due to immune complex deposition

What is anti-smith (Sm) and anti-ribonucleoprotein antibody (anti-RNP)?

- Anti-Sm found in 10-40% of pts with SLE, but very infrequent with other conditions --> if negative, does not exclude SLE dx

- Anti-RNP found in 40-60% of pts with SLE, but not specific for SLE

Both titers do not correlate significantly with any clinical activity of the disease --> not usually ordered

What is rheumatoid arthritis (RA)?

- autoimmune dz that attacks tissues near joints and other body party

- sx: chronic swelling and pain

- usually affects joints symmetrically --> most frequently in the hand