! Flashcards
Differentiate systemic vs localized amyloidosis
-What organ is mostly affected causing what condition
-other conditions
Kidney (nephrotic)
Restrictive cardiomyopathy, tongue enlargement, malabsorption, hepatospleenomegaly
I. SYSTEMIC AMYLOIDOSIS
A. Primary amyloidosis is systemic deposition of AL amyloid, which is derived from immunoglobulin light chain.
1. Associated with plasma cell dyscrasias (e.g., multiple myeloma)
B. Secondary amyloidosis is systemic deposition of AA amyloid, which is derived from serum amyloid-associated protein (SAA).
1. SAA is an acute phase reactant that is increased in chronic inflammatory states,
Ibd, RA, Sle
malignancy, and Familial Mediterranean fever (FMF).
2, FM is due to a dysfunction of neutrophils (autosomal recessive) and occurs in persons of Mediterranean origin.
i. Presents with episodes of fever and acute serosal inflammation (can mimic
Neu trigger inflam
appendicitis, arthritis, or myocardial infarction) it. High SAA during attacks deposits as AA amyloid in tissues.
C. Clinical findings of systemic amyloidosis include
1. Nephrotic syndrome; kidney is the most common organ involved.
2. Restrictive cardiomyopathy or arrhythmia
3. Tongue enlargement, malabsorption, and hepatosplenomegalv
D. Diagnosis requires tissue biopsy. Abdominal fat pad and rectum are easily accessible biopsy targets.
B. Damaged organs must be transplanted. Amyloid cannot be removed.
I. LOCALIZED AMYLOIDOSIS
A. Amyloid deposition usually localized to a single organ.
B. Senile cardiac amyloidosis
1. Non-mutated scrum transthyretin deposits in the heart.
2. Usually asymptomatic; present in 25% ofindividuals > 80 years ofage
C. Familial amyloid eardiomyopathy
L. Mutated serum transthyretin deposits in the heart leading to restrictive cardiomyopathy
2.
5% ofAfrican Americans carry the mutated gene.
D. Noiv-insul in- dependent diabetes mellitus (type II)
i, Aniylin (derived from insulin) deposits in the islets ofthe pancreas,
E. Alzheimer disease
1. Ali amyloid (derived from (J-amyloid precursor protein) deposits in the brain forming amyloid plaques,
2. Gene tor (5-APP is present on chromosome 21. Most individuals with Down syndrome (trisomy 21) develop Alzheimer disease by the age of40 (carly-onset).
F. Dialysis-associated amyloidosis
1, ^-microglobulin deposits in joints,
G. Medullary carcinoma ofthe thyroid
1. Calcitonin (produced by tumor cells) deposits within the tumor (‘tumor cells in an amyloid background’)
BOY with a normal lymphocyte count with decreas immunoglobulins except IgM
Moi
Pathophysiology
What bugs?
Treatment / treat bug
HyperIgm
- x linked recessive
- cd40l/cd40
- p. Jiroveci (tmp-smx and steroids )
-IVIG
1 month old boy, viral, fungal, bacterial issues
Pathophysiology
MOI
Treatment
SCID
-IL-2 deficiency (XLR) can’t proliferate b or T cells
-ADA deficiency (AR)
Bone marrow transplant and recombinant enzyme ( enzyme if Ada def
Boy with petechiae, bleeding , exchymosis and inc infections, eczema
MOI
PATHOPHYSIOLOGY
XLR
wasp mutation therefore problem with leukocyte cytoskeleton on wbc so can’t phagocytosis
Boy with decreased lymphocyte count and decreased all immunoglobulins
MOI
Pathophysiology
BUGS
TREATMENT
Briton’s - BTK mutation
XLR
IVIG
Bacterial , enterovirus (polio and coxasackie, giardia
What heart conditions in digeorge
TOF, truncas arteriosus
Paroxysms of lip edema, abdominal pain
Diagnosis
Treatment
Hereditary angioedema because c1 inhibitor deficiency- increase bradykinin
- abdominal pain because of GI mucosa edema
Ecallantide- inhib kallikren
Icatibart- inhibit bradykinin receptor
Chediak
Pathophysiology
Symptoms
LYST mutation (microtubule therefore can’t produce phagolysome
- silver hair/ sunburns indicates albinism, sinopulmonary infections, staph aureus infections
- giant granules in blast cells
LAD
Pathophysiology
Symptoms
Issue with integro a (LFA1, MAC1, dialup Lewis x
Delayed umbilical separation
Increases wbc
Skin infections without pus
Defective transmigration
CVID
Treatment
Pathophysiology
Bugs
Complication
Decreased immunoglobulin due to b and T cell deficiency
Other autoimmune disorders and lymphoma
IV. COMMON VARIABLE IMMUNODEFICIENCY (VID)
A. Low immunoglobulin due to B-cell or helper T-cell defects
B. Increased risk for bacteria], enterovirus, and Giardia lamblia infections, usually in late childhood
CGD
PATHOPHYSIOLOGY
MOI
SYMPTOMS
BUGS
DIAGNOSIS
TREATMENt
Napdh oxidase deficient -XLR
recurrent staph aureus abscesses or abscesses with catalase positive organisms - Aspergillous, Cándida, no ardía, burkholderia, pseudomonas cepacia, serraría
Nitro blue tetrazoliym - if no change in color to blue then negative test confirming cgd
Dihydrorhodamine 123 assay- no change in fluorescence equals CGD
TREATMENT -IFN gamma to stimulate macrophages since neutrophils aren’t helpful
30.22 yo Caucasian F presents to the ED with a 3 day h/o productive cough, SOB, and high fevers.
Over the last 6 years, she has had 5 episodes of pneumonia and has required many courses of vancomycin therapy for S. Aureus bronchitis. She was previously diagnosed with malabsorption that failed to improve with gluten exclusion from the diet. Labs are notable for decreased serum IgG and IgA levels.
Dx:
Tx strategies:
Most important complication of this disorder:
Dx: CVID
Tx strategies: IVIG
Most important complication of this disorder: Al diseases
SLE
- antibodies (what do they tell you )
- MCCOD
- MC renal disorder
- what syndrome is it associated with? (Complications and treatment
Drug induced lupus
- antibodies
- differentiate it from SLE
- Drugs
SLE- ANA/ anti dsdna
- dsdna tells prognosis and renal involvement
- MCCOD: renal and infections
(They also have accelerate atherosclerois at young age
- MC renal disorder membranoproliferative
- associated with anti phospholipid syndrome - anti cardiolipin and anti lupus antibody can give false positive Syphillis and falsely elevate PTT, hepatic vein thrombosis, DVT, thrombosis of placenta hence miscarriages
life long anticoagulation
Drug induced lupus
- ANA, antihistone
- no cerebral or renal involvement
- drugs: HIP, sulfa, ethanecrept, phenytoin
Sgrogren
Antibodies
Complications
Antibodies -ANA and anti ribonucleo protein (SSA and SSB), rheumatoid factor event if don’t have RA
Neonatal lupus (rash hepatitis , anemia, thrombocytopenia and third degree heart block ; extraglandular manifestations (RA or other autoimmune
B cent marginal zone lymphoma - unilateral enlargement of parotid gland much later in life
Scleroderma
MCCOD
Most commonly affected organ
Antibodies
MCCOD:Pul HTN
Most affected organ - esophagus (dysmoyility issues leading to dysphasia) and GERD
Antibodies - diffuse ( ANA and anti dna top(scl-70 and local(Centromere)
Crest is localized to hands - nail pitting
ITP
pathophysiology
2 forms(and causes)
Labs
Treatment
Autoimmune production of IgG against pl proteins (glycoprotein 2b/3a). IgG produced in spleen and spleen eats platelets
Acute- kids weeks after viral infection or being vaccinated (self resolves in weeks; adults (female maybe with SLE); since igG can go into the placenta it can cause transient thrombocytopenia in fetus
Dec pl, inc BT, normal PT/PTT
TREATMENT - steroids first b) IVIG c) splenectomy
HUS/TTP
pathophysiology
Symptoms
Treatment
HUS - drug or infection (ecoli >shigella toxin damages the endothelial and causes decreased adamst13 and TTP- antibody against adamst13 aka vwf metalloprotease (autoimmune disease so can’t inactivate vwf
Fatrn - renal involvement bc of renal thrombosis more in HUS and thrombus in cerebral vessel causing neuro symptoms in TTP
Treatment (TTP-plasmapheresis 2) IVIG
(HUS/ supportive no antibiotics please bc worsens things
Other qualitative problems and glanzmann and Bernard (MOI, lab, what drug acts like Glanzmann
Aspirin bc decreases txa2
Uremia affects platelet function
Bernard- gp1b (AR) , Bt inc, NORMAL PT/ PTT, abnormal risocentin
Glanzmann (gp2b/3a (AR)
Bt inc, NORMAL PT/ PTT, risocentin normal , abcximab
Coagulation factor inhibitor
Usually inhibits factor 8
But PTT doesn’t increase even if given someone else’s plasma
Vwd
MOI
Symptoms
Labs
Treatment t
AD
Mild mucosal( GIb , hemoptisis, menses, nose( and skin bleeding but rarely deep bleeds
BT increase, Normal PT/PTT, riscocetin assay is abnorma
Tx: Desmopressin
Causes of DIC
Labor release thromplastin tissye which activates extrinsic (7), adenocarcinoma, APL
Disorder of fibrinolysis (differentiate from DIC with labs
Plasmin inactivated pl aggregation , coag cascade, cleaves fibrinogen
Normal platelet count, increase Bt, inc PT/PTT, no increas in Ddimers because fibrin is not cleaved
Causes of thrombosis
Immobilization
Cardiac wall dysfunction- afib
Aneurysm
Atherosclerois
Vasculitis
Homocysteinuria
Treatment of Hit
Pathophysiology
F2 inhibitors/ direct thrombin inhibitors-Argatroban, davigatran, bivalirudin
Rare - F10 inhibitor (apaxiban)
Heparin binds platelet factor 4 and uses up all of the platelets and activates platelets hence hyper coagulation
