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Clinical Science > Labs of Inflammation and Autoimmune Disease > Flashcards

Labs of Inflammation and Autoimmune Disease Flashcards

1
Q
  • Describe false positive
  • Describe false negative
A
  • person who is free of disease/condition (healthy) that tests positive for a condition
  • person who has the disease/condition (affected/sick) that tests negative for that condition
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2
Q
  • Tests that are sensitive give you what?
  • Tests that are specific give you what?
A
  • true positives (you ARE sick, are you)
  • true negatives (you ARE healthy, or are you)
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3
Q
  • Describe sensitivity.
  • A test with high sensitivity picks up more (…) and has few (…)
  • A test with low sensitivity has many (…)
A
  • how sensitive is the test at correctly identifying our truly “sick” or positive pts (picking up actual disease
  • more true positives; few false negatives
  • many false negatives
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4
Q
  • What is the sensitivity of the rapid antigen COVID test? Describe this if we test 100 people
  • What is the sensitivity of the influenza tests? Describe this
A
  • about 95%; out of 100 sick pts, 95 will have a true positive while 5 may have a false negative
  • 50-70%; we miss out 30-50% of actual sick pts
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5
Q

A highly sensitive test will “pick up” on the presence of disease because it is sensitive to the (…); the test does not give up many (…), so we know that our result is one we can count on

A
  • condition
  • false negatives
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6
Q
  • Describe specificity.
  • A test with high specificity means the test is specific for that (…), and you will not get many (…) due to other conditions that may be present
  • A test with low specificity will be more difficult to interpret because there can be (…) and it is not specific for (…); therefore, you are getting many (…) for the condition you are seeking
A
  • how specific is the test for the diagnosis I am looking for
  • one condition; false positives
  • a variety of causes; one condition; false positives
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7
Q
  • If my alkaline phosphatase is elevated, is it specific for one condition or possibly several?
  • If my influenza test is positive, could I really have covid?
  • If I have leukocytosis on a CBC, does that always mean the pt has a bacterial infection?
A
  • no, there are possible reasons for an elevated phosphatase
  • no, the specificity of the influenza test is 100%
  • no, elevated WBCs are non-specific so there can be many reasons
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8
Q

What is a non-specific marker of infection and/or inflammation?

A

erythrocyte sedimentation rate (ESR)

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9
Q
  • What is the erythrocyte sedimentation rate commonly referred to as?
  • Is this test specific or non-specific?
  • What is this test used as a marker for?
  • This test is often used as part of a (…) of vague symptomatology
A
  • ESR or “sed rate”
  • non-specific; not diagnostic and not specific - only shows part of the picture
  • inflammation, infection, tissue infarction and necrosis, neoplasm
  • diagnosis
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10
Q

Describe the pathophysiology behind the ESR test

A
  • erythrocytes are negatively charged and therefore repel each other
  • in cases of inflammation/infection, the body releases APRs, including fibrinogen and immunoglobulins (antibodies)
  • these APRs are positively charged and increase the surrounding positive charge around the erythrocytes
  • this changing environment around RBCs to more neutral leads to “stacking of RBCs” called Rouleaux formation
  • Rouleaux formation often indicated the presence of inflammation or infection
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11
Q

In a sed test, the lowest values are (…), when you have inflammation, the value (…) because it is becoming (…)

A
  • at the top
  • falls
  • higher
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12
Q

How is the ESR test performed?

A
  • blood is aspirated into sedimentation tube
  • blood separates into plasma and RBCs over course of 60 mins
  • the amount “settling” of RBCs is measured
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13
Q
  • What is the normal value of the ESR test?
  • Higher levels corresponds to what?
A
  • 0-20 mm/l
  • more stacking of RBCs = more antibodies/inflammation
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14
Q

Wat are RBC factors that increase ESR? Why?

A

anemia - except sickle cell
- less erythrocytes are present
- results in RBCs “falling down” farther in the tube
- higher ESR results

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15
Q

What are RBC factors that decrease the ESR? Why?

A

sickle cell anemia
- abnormally shaped, sickled RBCs do not fall down the tube well
erythrocytosis/polycythemia
- underlying condition results in abundance of RBCs to fill up the tube to a lower value on ESR

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16
Q

What conditions elevate ESR?

A
  • inflammatory states
  • autoimmune disease
  • obesity
  • malignancy
  • age
  • infection (moderate to severe)
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17
Q

If pts ESR is greater than 100, they most likely have an overwhelming (…) and could have a fatal outcome

A

bacterial infection or cancer

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18
Q

C-reactive protein test is a (…) marker of infection and/or inflammation

A

non-specific

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19
Q
  • C-reactive protein is a (…)
  • What is the function of the C-reactive protein?
A
  • positive APR
    function
  • recognize/respond to inflammatory mediators and target damaged tissue for clearance
  • stimulated by cytokines IL-1, IL-6, and TNF
  • activates the complement system
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20
Q
  • C-reactive protein is elevated in inflammatory states, but not (…) for any disease
  • C-reactive protein is synthesized in the (…) so in (…), it is unreliable as an indicator of infection/inflammation
  • What is the reference range of C-reactive protein?
A
  • not specific
  • liver; liver failure
  • 8-10 mg/L
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21
Q

A CRP level above 10 mg/L is likely to be significant. and a level about 50 mg/L is a fairly sensitive and specific indicator that there is (…) present

A

an overwhelming bacterial infection

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22
Q

What can cause a mild (>10) CRP value?

A
  • mild respiratory infection
  • pregnancy
  • post-exercise
  • obesity
  • depression
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23
Q

What can cause a mild (10-50) CRP value?

A
  • MI
  • malignancy
  • autoimmune disease(s)
  • rheumatoid arthritis
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24
Q

What can cause a marked (>50) CRP value?

A
  • overwhelming bacterial infection
  • severe trauma
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25
Q

What determines whether we used ESR or CRP?

A

half-life and duration of illness

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26
Q
  • ESR is based on the presence of (…) and (…) which have (…) half-lives
  • What is the half-life of fibrinogen?
  • What is the half-life of IgG?
  • ESR is more commonly used in (…)
A
  • fibrinogen, IgG, longer half-lives
  • 100 hours
  • 7-21 days
  • chronic inflammatory processes
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27
Q
  • CRP increases and decreases (…) once inflammation or infection resolves
  • Levels increase in (…) hours
  • Levels peak at (…) hours after inflammation starts
  • CRP is more commonly used in (…)
A
  • quickly
  • 4-6 hours
  • 36-50 hours
  • acute infection/inflammation
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28
Q

What conditions could you order ESR for?

A
  • eval of autoimmune diseases/widespread joint pain:
    ** lupus
    **rheumatoid arthritis
    **crohn’s disease
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29
Q

What conditions could you order CRP for?

A
  • bacterial pneumonia
  • cellulitis
  • sepsis
  • septic joint
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30
Q
  • Procalcitonin is a precursor of (…)
  • Procalcitonin levels increase during (…) but not (…) infections
  • In which settings do we commonly use procalcitonin tests?
  • What is the purpose of using procalcitonin tests in these settings?
  • Procalcitonin tests are more frequently used in evaluation of what?
A
  • calcitonin (regulator of calcium)
  • systemic bacterial, but not viral, infections
  • hospital settings (not cost-effective)
  • distinguishing b/w viral and bacterial origin of cough in hospitalized pts; reduce use of inappropriate antibiotics
  • sepsis; severe infection w/ unknown origin or if diagnosis is in doubt
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31
Q

If a patient presents with a lower respiratory tract infection, what test can you order?

A

procalcitonin

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32
Q

What are some drawbacks to using PCT (procalcitonin) to guide antibiotic use?

A
  • more likely to be evaluated in severe pneumonia, but not necessarily all pneumonias
  • many pts with pneumonia have co-existent and simultaneous viral and bacterial pathogens present
  • use of PCT hasn’t been shown to improve cure rates, lengths of hospital or ICU stays, or reduce mortality rates
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33
Q

What can be defined as a broad-spectrum of illnesses caused by development of autoimmunity, or self-reactivity?

A

autoimmune disease

34
Q

Describe some aspects of autoimmune disease?

A
  • development of antibodies against self-antigens or “host” where body fails to recognize its own tissue
  • can be mild to severe w/ consequences of inflammation and cause damage to tissues or organs
35
Q
  • In order to diagnose, we may search for specific antibodies that cause a specific or suspected disease. What are ones most commonly used?
  • We can also measure other markers of inflammation which includes?
  • It is important to utilize these tests in conjunction with (…)
A
  • rheumatoid factor (RF) and ANA (anti-nuclear antibody)
  • ESR and CRP
  • complete history and physical
36
Q

How do we diagnose autoimmune disease?

A
  • history
  • physical examination
  • autoantibodies
  • markers of inflammation
37
Q

What are some different autoimmune disorders?

A
  • rheumatoid arthritis
  • systemic lupus erythematosus
  • sjogren’s syndrome
  • scleroderma
  • hypothyroidism/hyperthyroidism
38
Q

What are some autoimmune laboratory tests?

A
  • erythrocyte sedimentation rate
  • C-reactive protein
  • antinuclear antibody
  • rheumatoid factor
39
Q
  • What typically affects one or many different joints, resulting in loss of joint space?
  • This often presents worse in (…) and is not typically (…) to pain
  • With this condition, patients complain of pain but have (…) symptoms
  • This is (…) condition and markers of inflammation do not apply and are not tested unless clinician is uncertain
A
  • osteoarthritis
  • one joint; equal symmetry
  • no systemic symptoms
  • not an autoimmune condition
40
Q

In rheumatoid arthritis, there is not only joint space (…), but also increased (…) in synovial fluid, ultimately resulting in severe (…) and (…)

A
  • narrowing
  • inflammation
  • joint erosion
  • deformity
41
Q

What is this describing:
- chronic, inflammatory condition
- involves synovial joint stiffness, pain, swelling, and ultimately deformity
- frequency affects MCP and PIP joints of hands
- occurs symmetrically

A

rheumatoid arthritis

42
Q

How is rheumatoid arthritis different from osteoarthritis?

A
  • caused by autoantibody destruction of joint tissue
  • has systemic mutations such as:
    **fatigue, cardiovascular, renal, many other systemic diseases
    **has ability to shorten lifespan, which OA does not
43
Q

What is a chronic inflammatory disease that affects multiple joints and organs and is caused by an autoimmune process?

A

systemic lupus erythematosus (“lupus”)

44
Q

What are the symptoms associated with systemic lupus erythematosus?

A
  • facial rash “butterfly rash”
  • fatigue
  • weight loss
  • arthralgias and myalgias
  • lymphadenopathy
  • multiple organ involvement (kidneys: lupus nephritis; brain/CNS: lupus psychosis - rare)
45
Q

What are the manifestations of the autoimmune disease called progressive systemic sclerosis (scleroderma)?

A
  • fatigue
  • arthralgias
  • myalgias
  • sick thickening and hardening
  • digital ulcers
  • multiple systemic manifestations
46
Q

What are the manifestations of sjogren syndrome?

A
  • diminished lacrimal and salivary gland function
  • dry eyes
  • dry mouth
  • vaginal dryness
  • rhinitis and sinusitis
  • lymphoma
47
Q

What measures the presence of autoantibodies towards own nucleic acids (DNA or RNA)?

A

antinuclear antibody test (ANA)

48
Q

ANA is important in the diagnosis of what?

A
  • systemic lupus erythematosus
  • also serves as an indicator of several other autoimmune diseases
49
Q
  • The antinuclear antibodies in the ANA test are identified through a complicated immunofluorescence technique called (…)
  • The highest dilution at which the (…) are detected is reported as a result
  • Less than (…) dilution is negative
  • Between is considered (…)
  • Greater than (…) is strongly positive
A
  • indirect immunofluorescence
  • antinuclear antibodies
  • 1:40
  • uncertain ground
  • 1:160
50
Q
  • What is the sensitivity of the ANA test with lupus?
  • What is the specificity of the ANA test with lupus?
  • What other diseases can trigger positive ANA?
  • What percent of cases of RN will have a positive ANA?
  • What percent of healthy people can have a false positive ANA?
A
  • 95% (95% of true lupus pts will have positive ANA)
  • 86%
  • rheumatoid arthritis
  • 30%
  • 14%
51
Q
  • What autoantibody tests are more specific for SLE (lupus)?
  • What other autoantibody tests are more specific for sjogren’s syndrome?
A
  • anti-phospholipid antibodies, anti-double-stranded DNA, anti-smitch antibody
  • anti-Ro/SSA, anti-La/SSB
52
Q
  • What is the primary lab test used to diagnose rheumatoid arthritis?
  • However, this is antibody is present in (…) of healthy individuals
  • Most common is our own (…) antibodies (but can be (…)) directed (…) the portion of our (…) antibodies known as the Fc fragment
  • (…) levels of RF with higher levels of disease activity/severity
A
  • RF antibodies
  • 1-5%
  • IgM, can be IgG or IgA, directed against, our IgG
  • increased
53
Q
  • The rheumatoid factor measures in lab test is the (…)
  • What is the sensitivity of RF to detect RA?
  • What is the specificity?
  • The RF can be evaluated in what other diseases?
A
  • IgM RF
  • 60-90% (lower sensitivity in those with milder disease)
  • 85%
  • Lupus and other autoimmune disease; infectious disease such as the flu, mono, hepatitis, TB; malignancy
54
Q
  • In thyroid disease, we do not typically use (…) to diagnose disease
  • What are some thyroid specific labs?
A
  • ESR and CRP
    thyroid-specific labs:
  • thyroid-stimulating hormone (TSH)
  • thyroxine (T4)
  • free thyroxine (free T4)
  • triiodothyronine (T3)
  • free triiodothyronine (free T3)
55
Q

What is the normal value of TSH?

A

0.5-5.0 ulU/mL

56
Q
  • The thyroid is a gland that is located (…) in the neck from the (…) vertebrae to the (…) vertebrae
  • The gland has a (…) due two its two lateral lobes connected by a medial (…)
  • Control of the thyroid gland is regulated by the (…) and (…)
A
  • anteriorly
  • C5
  • T1
  • butterfly-like
  • isthmus
  • hypothalamus
  • pituitary gland
57
Q
  • What is thyrotropin-releasing hormone (TRH) synthesized?
  • Where is it transported to?
  • What does it stimulate the secretion of?
  • TSH binds to the receptors of the (…) and stimulated the release of (…)
  • These are (…) and (…)
  • What do these do?
A
  • hypothalamus
  • pituitary
  • TSH
  • thyroid gland
  • thyroid hormones
  • triiodothyronine (T3) and thyroxine (T4)
  • influence the metabolic rate of the body and many metabolic processes
58
Q
  • What is T4 converted to?
  • If you have an excess of T3, what will increase?
A
  • T3
  • cardiac and metabolic processes increase
59
Q

What do thyroid hormones affect?

A

nearly all tissues and involved in growth, metabolism, and heart rate

60
Q

Increase of T3 and T4 leads to what?

A
  • myocardial contractility and heart rate
  • mental alertness
  • ventilator drive
  • bone turnover
  • GI motivity
61
Q
  • What measurement is used to test and assess the function of the thyroid gland?
  • This sensitively measures either (…) or (…)
A
  • TSH level
  • thyroid hormone deficiency or excess
62
Q

In conjunction with T3 and T4, TSH levels can usually identify the origin of thyroid dysfunction in what disorders?

A
  • primary hypothyroidism
  • secondary hypothyroidism
  • tertiary hypothyroidism
63
Q
  • Describe primary hypothyroidism?
  • Describe secondary hypothyroidism?
  • Describe tertiary hypothyroidism?
A
  • disorder occurs at the level of the thyroid; most common = 99% of cases
  • disorder occurs at the level of the pituitary; uncommon, pituitary tumor
  • disorder occurs at the level of the hypothalamus; rare, hypothalamic tumor
64
Q
  • What is the most common cause of hypothyroidism?
  • What is this caused by?
  • What are other causes of hypothyroidism?
A
  • autoimmune thyroiditis (Hashimoto’s thyroiditis)
  • autoimmune destruction and apoptosis of thyroid cells by TSH stimulation blocking antibody
    other causes:
  • iodine deficiency
  • thyroidectomy
  • radiation to the neck
  • treatment for hyperthyroidism
65
Q

What are some symptoms of hypothyroidism?

A
  • fatigue
  • dull mentation
  • dry skin
  • weight gain
  • bradycardia
  • constipation
  • cold intolerance
66
Q
  • In order to further delineate the causes of hypothyroidism or hyperthyroidism, we need to examine (…)
  • Measurement of (…) help to elucidate further causes or the origin of the disorder
A
  • the thyroid hormones themselves
  • T3 and T4
67
Q
  • The thyroid produces what hormones?
  • What are the percentages associated with these hormones produced?
  • T4 is then converted to (…) in what tissues?
A
  • T4 (90%) and T3 (10%)
  • T3 - liver, kidneys, muscles
68
Q

What is more metabolically active than T4?

A

T3

69
Q
  • T4 makes up (…) of thyroid hormones
  • Nearly all of T4 is (…)
  • What is it bound to?
  • (…) is the remaining, unbound, metabolically active form of T4
  • When there is an abnormality of the proteins that bind T4 or factor that increased TBG, (…) is stable and may be a more accurate reflection of thyroid function than (…)
A
  • 90%
  • protein
  • thyroxine binding globulin, albumin, transthyretin
  • free T4
  • total T4
70
Q
  • T3 makes up (…) of thyroid hormones but is more (…) than T4
  • What percentage of T3 is bound to proteins?
  • Therefore, the amount of (…) in circulation is small, but it is more (…) than T4
  • T3 is also formed in the tissues by conversion of (…)
A
  • 10%
  • 70%
  • free T3
  • more metabolically active
  • T4 to T3
71
Q
  • What should you measure if you suspect hypothyroidism?
  • In hypothyroid states, the serum TSH is elevated and in those conditions, the thyroid prefers to release (…) so it remains (…), even in the face of disease
  • So as hypothyroidism progresses, (…) increases, then (…) decreases, and the last holdout is (…)
A
  • serum free T4
  • T3
  • remains constant
  • TSH increases
  • T4 decreases
  • last holdout is T3
72
Q

How do you differentiate primary and central hypothyroidism?

A
  • measure TSH and free T4
  • if TSH is decreased AND T4 is decreased, then hypothyroidism may result from disorder of the hypothalamus or pituitary gland (failure at the factory)
73
Q

Describe subclinical hypothyroidism?

A
  • “milder” hypothyroidism but symptoms similar, can be vague, non-specific symptoms
  • patient may have high normal or mildly elevated TSH with normal free T4
  • frequently will progress to overt hypothyroidism
  • treatment with thyroid replacement medication is somewhat controversial
74
Q
  • What are two different forms of hypothyroidism?
  • What are their associated TSH and T4 levels?
A
  • overt hypothyroidism; high serum TSH, low serum free T4
  • subclinical hypothyroidism; high serum TSH, normal serum free T4/T3
75
Q
  • Increased TSH, decreased T4 is what?
  • Increased TSH, normal free T4 is what?
  • Normal/decreased TSH, decreased free T4 is what?
A
  • primary hypothyroidism
  • mild/subclinical hypothyroidism
  • central hypothyroidism
76
Q
  • Hyperthyroidism is also called (…) and is (…) found than hypothyroidism
  • Hyperthyroidism is caused by (…) secretion of thyroid hormones by thyroid gland
  • The most common form of hyperthyroidism is called (…)
  • Hyperthyroidism causes an inhibitory effect on the hypothalamic-pituitary axis and (…) decreases
A
  • thyroxicosis
  • less commonly found
  • increased secretion
  • Grace’s disease
  • TSH level decrease
77
Q

What is caused by autoantibodies (TSH receptor antibody or TRAb) that bind and activate TSH receptors of the thyroid gland?

A

Grave’s disease

78
Q

What can hyperthyroidism also caused by?

A
  • hyperplasia of thyroid cells whose function is not regulated by TSH (toxic adenoma (benign growth), toxic multinodular goiter)
  • iodine rich medication (amiodarone-cardiac medication, iodine-based contrast dye used in CT scans)
79
Q

What are symptoms of hyperthyroidism?

A
  • anxiety
  • tremors
  • palpitations
  • perspiration
  • heat intolerance
  • weight loss despite normal appetite
  • hyper-defacation
80
Q
  • All patients with primary hypothyroidism have a (…) including those with subclinical hypothyroidism
  • Subclinical hyperthyroidism may have (…) symptoms
A
  • suppressed TSH
  • non-specific, or milder, symptoms
81
Q

If TSH is low or if suspicion high at initial visits, what should you add to test?

A
  • T3
  • free T4
82
Q
  • Low TSH, high free T4 and T4 is what?
  • Low TSH, normal free T4 and T3 is what?
A
  • overt hyperthyroidism
  • subclinical hyperthyroidism

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