! 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
IDA labs (associated what what GI pathology)
Serum fe
Transferrin sat%
Ferritin
TIBC
RDW
FREE ERYTHROCYTE PRotoporhyrin
Dec serum fe , Dec transferrin sat, inc tibc , Dec ferritin, inc FEP , inc RDW(size difference
Plummer Vinson syndrome
Remember starts off low stored fe- ferritin low inc TIBC
Then low serum fe - low serum fe and saturation
Normoxytic anemia - bone Marrow produces fewer but narrow sized rbc
Then microcytic hypochromic anemia - bone marrow produces fewer but smaller rbc
ACD
Seen in what conditions
Serum fe
Transferrin sat%
Ferritin
TIBC
FREE ERYTHROCYTE PRotoporhyrin
EPO
Serum fe low
Transferrin sat% low
Ferritin high
TIBC low
FREE ERYTHROCYTE PRotoporhyrin high
EPO low
Inflammatory: autoimmune or cancer
Sideroblastic
Causes
Labs (similar as what condition)
- Serum fe m
Transferrin sat%
Ferritin
TIBC
Congenital - ALAS enzyme deficient; Acquired- alcoholism,
InH/vitamin B6 deficient, lead poisoning bc inhibits ALAD and ferrochetalasw
Serum fe high
Transferrin sat% high
Ferritin high
TIBC low
Similar as hemochromatosis
Alpha thalassemias
- types
- protected against what
One deletion- no problems
2 deletion on same chromosome 16 (cis) or deletion on separate chromosome 16- mild anemia and increased Rbc
- cis: child can get severe thalassemia, spontaneous abortions
Three deletions - beta 2 joins another beta 2 forming tetramers that damages the RBC -HBH
4 deletions - gamma4 tetramers (Hbbarts damages rbc)- hydrops fetalis
Protected against Plasmodium falciparum malaria
Beta thal
- types of hgb seen in major and minor
- blood smear results
- major : symptoms/ at risk for what infection
Minor - hgb (slight decrease of HgbA, increased Hgb A2 5% and HgbF 2%
- blood smear - microcytic hypochromic Rbc and target cells
Major - HbF is protective initially so symptoms present few months after birth
- Hgb- no or few HgA, increased hgbA2 and increased HgbF
- alpha tetramers damage the Rbc causing extravascular hemolysis bc spleen kills damaged RBC and extramedullary hematopoiesis in the skull, facial bones, liver and spleen
- parvo
- smear: microcytic hypochromic Rbc and target cell and nucleared RBC
Macrocytic anemia
- types (megalo or non)
-labs
- cause of megalo or non
Symptoms
Megaloblastic (12 or 9 def) or non (alcoholism, liver disease and drugs such as 5Fu
- megalo - enlarged rbc bc impaired division, impaired division of granulocyte therefore hypersegmebted neutrophils >5, epithelial cells large
Inc methylmalonic (causes SCD bc damages myelin in b12 deficiency) inc homocysteine in both 9 and 12 deficiency
B9- alcoholics or poor diet (stored in jejunum
B12 - vegans , pernicious anemia (autoimmune destruction of parietal cells in stomach so low IF, pancreatic insufficiency, damage to terminal ileum - chrons, sushi worm
Both causes glossitis
Increased risk of parvo Infection with what WBC disorder
Treatment
Different ways parvo presents
Bthal major
HS
Sickle cell
Supportive
Fever with rash on cheeks, joint pain in adults, very sudden drop in hgb in someone with hemoglobin problems (and had URI
HS
- pathophysiology
- labs
- what kind of hemolysis
- diagnosis
- treatment
Scandavivian AD
- Defectivw anchoring proteins therefore rbc bleb creating sperocytes in which the spleen eats the RBC
- extravascular hemolysis -inc unconj bili therefore jaundice and bili gallstones, anemic with splenomegaly
Labs: inc unconj bili, inc RDW and Inc MCHC (more concentrated hgb because rbc gets smaller )
Osmotic fragility test - bursts or eosin 5 malenic assay
Tx: splenectomy (would have Howell jolly remnants
Sickle cell
- pathophysiology
- what kind of hemolysis ?
- complications
- MCCOD in kids and adults
- symptoms in sickle cell trait
- hgb electrophoresis makeup
Treatment
- glutamic acid replaced by valine
- both extra and intra
Extra: increased unconj bilirubin therefore jaundice and bili stones, anemia with splenomegaly
Intra- Dec haptoglobin, inc bilirubin in urine and blood, increased inc hemosiderrin in urine ; extra medullary hemopoeisis in head and facial bones and spleen and liver ( enlarges those areas - MCCOD : kids ( autospleenectomt causes S. Pneu, h. Inf infection); adults ( acute chest syndrome - pneumonia or lung inf triggers chest pain and soB
Complications - dacrylitis (swollen hand and feet bc of vasoocclusive infarcts , ACS, renal papillary necrosis with hematuria and proteinuria, autospleen (Howell jolly as a result) - trait: <50% HbS sickle only in renal medulla due to hypoxia causing infarction in kidney therefor hematuria and can’t concentrate urine
- electrophoresis
Disease: HBS 90%, HbA2 2% HBF 8%
Trait : HbA 55%, HBS 43%, HbA2 2%
Treatment - hydroxyurea, folate bc deficient, penicillin to prevent against strep pneumonia meningitis
PnH
- pathophysiology
- what kind of hemolysis
- MCCOD
- diagnostic
- complications
No Gpi therefore no DAF to protect wbc rbc and platelets when you’re sleeping (resp as acidosis)
- intravascular hemolysis ( low haptoglobin, High hemoglobin in urine and blood, high hemosiderrin in urine)
- MCCOD- thrombosis in cerebral, hepatic an portal veins ( destroyed platelets release contents into the blood)
- complications : IDA (loss of fe in urine when lose hemoglobin in urine ); AML
Diagnosis - acidifies serum test / flow cytometry (look for CD55/DAF/ sucrose test
G6PD
- MOI
- pathophysiology ( what drugs)
- what kind of hemolysis
- diagnostic
XLR
Dapsone primaquine, sulfa , fava beans cause oxidative stress causes hgb to become Heinz bodies and spleen eats these Heinz bodies creating bite cells
Intra vascular
Enzyme studies weeks after episode resolves
immune hemolytic anemia
- types (what are the causes/ what lo for hemolysis
- diagnostic
- treatment
Warm (IgG antibodies BINDS RBC in WHICH the spleen eats the surface creating a spherocyre ; extravascular hemolysis: caused by SLE, CLL , penicillin and cephalosporins
Cold (IgM binds rbc and fixes complement especially in extremities (finger and toes in cold temperature ; intravascular; caused by mycoplasma pneumoniae and mono
Diagnostic : direct coombs
Treatment (warm: steroids , IVIG , if necessary splenectomy
Cause of microangiopathic anemia (plus what type of hemolysis
HUS, TTP, DIC, HELLP, aortic stenosis, prosthetic valve
- intravascular hemolysis
Mono
- causes
- what’s infected
- symptoms
- diagnostic
ebV mainly but sometimes cmv
Infects oropharynx (pharyngitis) B cell, liver (hepatitis, large liver and inc liver enzymes
- lymphadenopathy, splenomegaly, hepatomegaly, pharyngitis
- diagnostic : mono spot test (IgM antibodies against animal rbc. If it’s negative then look for EBV viral capsid antigen
ALL
- patient profile
- unique features of B- ALL and T- All
- which lymphoma can progress to this ?
Lab:
Usually >5 years old person with Down’s syndrome
- B-All - prophylaxis chemo in scrotum and head bc chemo can’t cross; bad prognosis in CML
- T-All : mediastibal /thymus mass called acute lymphoblastic lymphoma
Pancytopenic bc immature lymphoid take over the bone marrow and head to blood (inc WBC
AML
- unique feature
- types? (Treatment for one of them )
- what conditions can progress to this
mPo aggregate and form Auer rods
- APL- (15;17) Auer rods can increas risk of DIC ; treatment atra
Acute monocytic anemia (infiltrates gums
Acute megakarocytic anemia - - DS <5
Myelodysplatix syndrome, CML, HS progress to it
Chronic lymphocytic leukemia
- pathophysiology
- CD #
- complications
- MCCOD
- transforms into 2 things
** Most common leukemia-**
Proliferation of naive B cells
- CD5 and 20
- complications : diffuse large B cell lymphoma
- infection ( hypogammaglobinemia)
- transforms into small lymphocytic lymphoma if involves lymph nodes and diffuse large B cell lymphoma
Hairy cell leukemia
- pathophysiology
- positive for what ?
- symptoms
- treatment
Proliferation of mature B cells
Trap positive
Trapped in spleen red pulp and bone marrow therefore no lymphadenopathy
Tx: cladribine (adenosine desminase inhibitor)
Adult T cell leukemia / lymphoma
- cause
- pathophysiology
- symptoms
HTLV1
- proliferation of mature cd4 T cells
- skin rash, generalized lymphadenopathy, hepatomegaly, lyric punched out lesions increasing calcium
Mycosis fungoides
- pathophysiology
- symptoms
Proliferation of mature cd4 T cells
- rash plaques nodules
Chronic myeloid leukemia
- pathophysiology
- interesting lab value
- what can it transform to
- treatment
- complications
(9;22) bcr- abl (tyrosine kinase always on
- increas basophils
- aml or All ( seen especially with spleen starts enlarging
-treatment : **imatinib and dasatinib **
- complications: gout bc of hyperuricemia ; fibrosis of bone marrow ; transform to acute leukemia
Polycytemia Vera
- pathophysiology
- mutation
- symptoms/complications
- treatment
- differentiate between reactive Polycytemia ( and what are the causes)
Jak2 mutation ; malignant proliferation of myeloid cells especially rbc a so pl and granulocytes are increased
- headache, blurry vision, flushed skin, itching after bathing bc inc histamine , venous thrombosis of hepatic, portal , and rural sinus
- complications: venous thrombosis , hyperuricemia/gout, fibrosis of bone marrow, transformation into acute leukemia
Tx: phlebotomy and second line is hydroxyurea
Reactive Polycytemia - lung, high altitude (inc Epo and low sa02 ) , rcc (inc Epo normal Sa02)
P. Verá (Dec EPO , normal Sa02
Essential thrombocythemia
- pathophysiology
- mutation
- symptoms
- treatment
Proliferation of platelets and other myeloid cells (rbc and granulocyte - neutrophil, eosinophil )
- jak 2 mutation
- bleeding and thrombosis
(Can cause stroke) - plasmapheresis and aspirin
Myelofibrosis
-pathophysiology
_ mutation
- symptoms
- blood smear
Proliferation of myeloid cells especiallly megakarocytes which produces fibrosis of the bone marrow so spleen has to make rbc but let’s immature rbcs leave and.can’t make enough of wbc pl rbc ) and if hematopoiesis occurs in bone marrow they become tear drop shaped
; JAK2 mutation
- splenomegaly bc spleen does hematopoyesis ; increased risk of infection thrombosis, and bleeding
Complication. hyperuricemia/gout, fibrosis of bone marrow, transformation into acute leukemia
Follicular lymphoma
- pathophysiology
- complication
- possible treatment
Proliferation of small B cells (Cd20) ; (14;18- ig heavy chain on 14 and bcl2 moves to 14 leading to inhibitor on of apoptosis )
Complication: Diffuse large B cell lymphoma.
Tx: rituximab ( anti cd20)
Mantle cell lymphoma
- pathophysiology
(11;14) cyclin d1 promotes g1/s transition; proliferation of small B cells (cd 20
Painless lymphadenopathy in lymphoma
Marginal zone lymphoma
- pathophysiology
- associated with what conditions
- subtype (+ cause)
Proliferation of small bcells (cd 20)
Sgrogren , hashimoto, h pylori gastritis
- subtype : maltosa is marginal zone lymphoma in mucosal sites so caused by h pylori gastritis - resolves if cure h pylori
Burkitt lymphoma
- pathophysiology
Proliferation of intermediate size B cells (cd20) ; (8;14) over express cmyc promoting cell growth
Diffuse large B cell lymphoma
- pathophysiology
- how does it arise
Proliferation of large B cells (cd20 )
- sporadic or transformed from follicular lymphoma or CLL
Hodgkin
- pathophysiology (+ Cd marker )
- types
Proliferation of B cells called reed and reed activated cytokines and inflammatory cells which create the bulk of the mass
Cd15 and 30
Lymphocyte rich- good prognosis
Poor - bad prognosis
Nodular sclerosis - enlarged cervical or mediastibal lymph node in you g adult especially female
Mixed - eosinophils
Multiple myeloma
-pathophysiology
- symptoms
- MCCOD
- treatment
Il- 6 causes inc plasma cell growth and immunoglobulin
Crab ( plasma cells activate osteoclasts therefore Lytic lesion in skull and vertebrae( fractures ) and bone pain
Renal - increase kappa light chain protein in kidney called vence Jones and cause renal failure
A- acd, systemic amyloidosis, infection
B bone pain
MCCOD: infection (monoclonal plasma cells produce the same antibodies
Tx: **Bortezomib **
MGUS / Waldensteom differentiate from Mm
-
MGUS (M spike only)
Waldenstrom - B cell lymphoma producing IgM
m spike bc increased IgM
- visual and neurological (stroke? Retinal hemorrhage
- bleeding bc viscous blood inhibits platelet aggregation
- plasmapheresis
Lettererer siwe vs eosinophilia granulosa vs hand schoff
Letter - making so skin rash and cystic skeletal defects
Eosinophilic - benign so no skin , pathological fracture
Hand - making so skin rash , diabetes inspidus , exophthalmos
Less than 10 years old with infrared lymphadenopathy
ALL
Budd chiari occurs in this hemarologic conditions
PNH
polycythemia Vera
Myeloid cells of different stages
Chronic myeloid leukemia
