Rheumatology. Flashcards
Explain rheumatology.
Old name
Rheu- flow of a current
ology- study of
Branch of medicine that deals with the treatment and diagnosis of rheumatoid diseases such as
cateogries-
Autoimmune diseaae (SLE, Sarcoidosis, Rheumatoid arthritis)
Autoinflammatory diseases
(Familial mediteranean fever, stills disease)
Crystalline arthritis (gout, pseudogout)
Metabolic bone diseases
(osteoporosis, pagets disease)
Pain syndromes
(Fibromyalgia, Rotator cutt off tear)
and Vasculitis
Explain Rheumatism.
Any disease with Pain and Inflammation of joint, muscle or connective tissues.
What are some bullet points you need to remember while studying rheumatology?
No single Blood test will confirm the diagnosis.
Just because a person have +ANA does not mean LUPUS the tests needs to be compatible or fit with the patients history and physical examination
What is the main diffrence between ANA and ANCA antibodies?
Both are blood tests used by doctors to help in the diagnosis of autoimmune disease.
Antineutrophil cytoplasmic antibody (ANCA) is a blood test commonly elevated in patients with diseases such granulomatosis with polyangiitis, microscopic polyangiitis, and EGPA/Churg-Strauss syndrome.
Antinuclear antibody (ANA) is a blood test most often elevated in patients with systemic lupus erythematosus (“lupus”), Sjogren’s syndrome, scleroderma, and other types of autoimmune diseases.
Explain Sensitivity while dealing with the lab test of someone you suspect have rheumatism?
Sensitivity- Among the total persons who have the disease, how many of their lab test shows true positive criteria
the lower is the number of the false negative FN (have disease but doesn’t show in result) the higher will be the sesitivity of test
also If the test is true negative (TN) the Patient in almost all of the cases will have no disease.
what if the patient have zero symptoms?
All the negatives are true negatives if you choose a high sensitivity test in patient with no symptoms.
Explain specificity.
How many with no disease actually have true negative criteria
if in a high specific test patient gets a true positive it means they have the disease
(+ most of the symptoms)
How wil you rule out and rule in a disease? (lupus)
If by the symptoms its very unlikely that the patirnt will have lupus we gotta rule out this disease– we will use a sensitivity test as every negative is a true negative.
Eg- ANA is a sesitivity test so negative ANA means no lupus
but positive ANA can indicate a lot of diseases
If by symptoms it is highly likely that a patient have lupus, we will need to rule IN the disease – use a specificity test as every positive is a true positive.
Eg- Anti ds-DNA test
Anti smith test
if positive you have lupus
What is antibody titre?
This test is used to detect how many antibodies an organism have made . High number of antiobody —-> high level of disease
we keep diluting the antibody solution to find till how much dilution the solution of antibody is capable of causing agglutination.
The higher dilution it takes= means the soution have a lot of antibody
so we have to diltute the solution a lot more to cause them to prevent agglutination :)
What is ANA antibody?
Anti nuclear antibody— Attack the components of the nucleus of the cells.
Detected in titres
higher the titre—> higher the chance of autoimmune disease
BUT higher the titre= does not mean high severity of disease
ANA is considered positive if the titre is higher than 1:80
healthy people can also have +ANA
we do the test using immunoflorescence or ELISA
ANA titre has nothing to do with the activity of the disease so you should not repeat the ANA test
Explain some rheumatic disease and their markers
SLE - should have +ANA
+anti ds-DNA
+anti smith antibodies
RA - Should have +ANA
+RF
+anti-CCP
Explain ESR and CRP?
High ESR and CRP (C reactive protien ) can be seen in any inflammatory disease.
However in case of Lupus CRP is low. C3 goes down before C4
What are the common complaimts of a rheumatolgy patient?
Joint- Pain, Stiffness and loss of function
skin- Rash, lesion, swelling or sweating
eye problems, bowel problems and maliganncy.
Rheumatoid arthritis pain is worse in the morning
osteoarthritis - worse in night
how will you do a general exam of a patient?
Overall apperarence (looks, mood, brain function (awake, alert, orientation and arouseness)
posture and gait
skin- normal, cyanosis ,color, lesions, rash
weight
body haor
face
in rheumatology we examine all body systems. We look for extra articular manifestations.
Which diseases can have positive ANA?
1) Drug Induced Lupus (100% sensitivity)
so if ANA Is negative it is a true negative and the patient doesn’t have the disease
2) SLE (98-100% sensitivity) 98-100% patient will have positive ANA
but if negative- true negative- rule out the disease
3) Mixed connective tissue disease (93-100%)
4) Scleroderma
5) Sjogren
6) Dermatomyositis/ polymyositis
7) Rheumatoid arthritis (40%)
Why is ANA not specific
Negative ANA can rule out diseases but positive ANA means nohing as it is positive in a lot of disease (even normally)
Specificity— not present in many diseases and a characteristic of only one specific disease.
Explain Anti ds-DNA test.
It is a specific test for SLE
if positive—- true positive—–person has disease
corellates with SLE activity (lupus nephritis)
NOT SEEN IN DRUG INDUCED LUPUS
Explain anti smith test.
Specific test for SLE
doesn’t corellateswith likelihood of renal disease.
What are some of the Specific ANA’S?
If we are doing a test for simple ANA it is sensitive
but if we are doing test for specific types or anti nuclear antibody (depending on the component of the nucleus they are attacking ) we can get specific ana test tha can be used to rule in a certain diseases.
Some specific ANA are
1) Anti ds-DNA and Anti smith for lupus (if positive-have disease)
2) Anti histone for drug induced lupus
3) ANti-centomere for limited scleroderma
4) anti RNA polymerase III for Scleorderma kidney
5) Anti SCL 70 (anti topoisomerase 1) for systemic sclerosis
6) anti SSA (anti RO) SLE and sjogren
7) anti SSB (anti LA) SLE and sjogren
(both of them can be transferred to baby from mother and can cause congenital heart block and neonatal lupus)
8) anti- U1 RNP for MCTD and SLE
Classify rheumatolical diseases
Inflammatory and non inflammatory
Inflammatory- all cardinal signs of inflammation (red hot pain swell loss of function)
symmetric (antibody affect all side equally)
worse in morning
ESR and CRP high (as they are acute phase reactants and go up with inflammatory response)
example RA
Non- Inflammatory- No cardinal signs of inflammation
asymmetric (side of body affected unequally)
worse in evening (as we go throughout the day the more joint is used and the pain is more)
ESR and CRP normal limits. example osteroarthritis (mechanical wear and tear)
Explain ESR and CRP.
High esr means sedimentation rate is high
some pro sedimentation factors that cause high ESR are high number of Fibrinogen and high Immunoglobins (AB)
high ESR can be seen in
Inflammation (IgG, Fibrinogen) (SLE and RA)
Infection (IgG and fibrinogen) (TB and RF)
anaemia (less RBC less negative charges repelling each other)
Macrocytosis (Larger is slower)
multiple myeloma
Waldenstorm
Anti sedementation factors are the negative charges on the surface of rbc
negative charges repel each other thus preveting roulex formation and decreaing the ESR
low esr can be seen in- hyperviscosity syndrome polycythemia sickle cell microcytosis spherocytoiss
Explain ESR-
roulex formation (one rbc on top of another just like stacking)
high roulex formation high ESR (sedimentation rate is fast)
normal ESR= for men 15mm/hr (15 mm of rbc is sedementing per hour)
for women- 20mm/hr
What is the best way to examine an inflammed joint?
Joint Fluid Aspirate “Athrocentesis” or Joint Puncture
do ESR and CRP correlate with the disese activity?
YES!!!! (For eg if you have RA and your ESR is 130/hr your body is done.)
they correlate with the treatment and severity of disease unlike titres.
What if the ESR and CRP is extremely high?
Think Infection, Maliganancy or Vasculitis
these test are more sensitive than specific as their are thousands of conditions that can cause elevated level of the acute phase reactants
in case of rheumatic diseases, high ESR and ZRP indicate inflammatory criteria for these diseases but doesn’t point out or rule in a specific disease
if these are within normal limits and we are testing for rheumatic diseases it indicates non-inflammatory cateogry of these group of diseases. Like osteoarthritis
What is C reactive protien? CRP
Synthesized in liver in response to IL-6 (by WBC and Malignant cells)
bacteria/dying cell/malignant cell/WBC/Adiposcytes————–> IL-6———–> liver———-> CRP synthesis
CRP goes and attach to its receptor PHOSPHOCHOLINE on the affected cell
Phagocytosis by macrophages
normal value– 0.8 to 3.0 mg/L
if we are treating someone with high ESR and CRP? Which one should normalize first?
CRP is by definition, REACTIVE, so it both builds and dissipates rapidly.
The sed rate is by nature, SEDENTARY, so it is slow. That’s the mnemonic.
The supporting facts are that the half-life of CRP is 19 hours, while in contrast, the half life of fibrinogen is FOUR DAYS and the half life of IgG is TWENTY-ONE DAYS!!.
Those rouleaux are not going to be able to unstick themselves from each other for a long, long time. I think of CRP as carry-on luggage, and rouleaux as a big stack of luggage that has to be checked.
Explain APR acute phase reactants
Made by liver during inflammation
high in inflm.
Low when it is cured
these are of two types–
positive APR- high in inflammation
help the immune system
fight microbes and engulfs them
trap them in local blood clots
ex- CRPs , complements, Caogulation factors and VWF
alpha 2 microglobulin, ferretin, hepicidin, ceruloplasmin, haptoglobin, alpha 1 antitrypsin
ESR can be considered an acute phase reactat even though it is a lab method. Half life is 7 days so it can be high even though inflammation is cured
half life of CRP is 7 hours :)
negative APRs- low in inflammation
liver decrease some of them as during inflammation high amino acids are needed to synthesize +APR
so by decreasing some of its syn components (-APRs) it can compensate
ex- albumin transferrin and antithrombin
is there any diagnostic value with high crp?
No in itself. High CRP must correlate with History, physical exam, other risk factors and other lab results
high CRP could indicate high RISK of cardiovascular diseases
patient with obstructive sleep apnea have high CRP and IL-6
Females who take oral contraceptives also have high CRP—> high risk of thrombosis especially if they smoke
IF a prgnant female sudenly have high CRP it could indicate obsterics complication
What is the diffrence between CRP, C-peptide and Protien C?
CRP is a marker of inflammation
c protein is an inhibitor of factor 8 and 5 in the coagulation process
c peptide is a chain of amino acides produced in beta cells of the pancreas , it comes from the clivage of proinsulin .
What are ANCAs? (Anti-Neutrophillic Cytoplasmic Antibodies)
AutoAntibodies (IgG) against the antigens in the Cytoplasm of the nueutrophils and monocytes
(ANA are against nucleus of any cell)
the best way to detect these are Elisa(best) and Immunofluroscence
accosiated with Small vessel Vasculitis
again they do not correlate with disease activity.
What are some types pf ANCA?
AnCA can have different patterns under Immunofluroscence
c-ANCA -
cytoplasmic ANCA / PR3 ANCA
(uniform cytoplasmic staining with no interlobular accentuation or no staining of nucleus)
cytoplasm is glowing and nucleus is dark
we can easily tell the diffrence between neurophil and monocyte by seeing shape of nucleus
cANCA targets Protinease 3
p-ANCA-
Perinuclear ANCA / MPO-ANCA
(perinuclear staining with extension to nucleus)
cytoplasm aroung the nucleus is glowing with some part of nucleus in it
we cannot diffrentiate between N and M
p-Anca is positively charged so these AB will gather around the nucleus that is negatively charged
myeloid lineage have myeloperoxdase enxyme that makes free radicals
free radicals are negatively charges=d so pANCA will attack myeloperoxidase (positive ANCA)
how do ANCA affect the neutrophils?
ANCA are serum antibodies Protinease 3 (attack by cANCA) and myeloperoxidases (attcked by pANCA) are present in the cytoplasm of the cell so the serum antibodies cannot attack the neutrophil and monocytes.
As IL-6 or TNFalpha activates the N and M cells, these PR3 and MYLOP goes towards the lipid membrane surface. As they go to surface they gets attacked by ANCA causing damage to cell.
Degranulation of the cells occurs that causes tissue damage (vasculitus)
Name the Vasculitedes and ANCA accociated with them.
C-ANCA—->
Granulomatosis with polyangitis (wegners)
p-ANCA—>
Goodpasture syndrome
microscopic Polyangitis
Eosinophillic granulomatosis with polyangitis (Churgg strauss)
Drug induced ANCA accosiated vasculitis
primary Pauci immune necrotizing crecentric glomeruonephritis (RPGN)
Inflammatory bowel disease
Primary sclerosing cholangitis
Autoimmune hepatitis tupe 1
