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
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)
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
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
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
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
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
8
Q
What is a non-specific marker of infection and/or inflammation?
A
erythrocyte sedimentation rate (ESR)
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
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
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
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
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
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
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
16
Q
What conditions elevate ESR?
A
- inflammatory states
- autoimmune disease
- obesity
- malignancy
- age
- infection (moderate to severe)
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
18
Q
C-reactive protein test is a (…) marker of infection and/or inflammation
A
non-specific
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
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
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
22
Q
What can cause a mild (>10) CRP value?
A
- mild respiratory infection
- pregnancy
- post-exercise
- obesity
- depression
23
Q
What can cause a mild (10-50) CRP value?
A
- MI
- malignancy
- autoimmune disease(s)
- rheumatoid arthritis
24
Q
What can cause a marked (>50) CRP value?
A
- overwhelming bacterial infection
- severe trauma
25
Q
What determines whether we used ESR or CRP?
A
half-life and duration of illness
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
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
28
Q
What conditions could you order ESR for?
A
- eval of autoimmune diseases/widespread joint pain:
** lupus
**rheumatoid arthritis
**crohn’s disease
29
Q
What conditions could you order CRP for?
A
- bacterial pneumonia
- cellulitis
- sepsis
- septic joint
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
31
Q
If a patient presents with a lower respiratory tract infection, what test can you order?
A
procalcitonin
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
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
