heme Flashcards
lead poisoning (MOA… leads to… )
- inhibition of both aminolevulinic acid dehydratase (leads to increased precursor) and ferrochelatase (final step in heme synthesis)
- lead-induced porphyria leads to microcytic (hemoglobin poor) anemia
most common primary cardiac tumor (name and histology, possible complication)
- atrial myxoma
- amorphous extracellular matrix
- associated with multiple syncopal episodes
CD4 marker
-helper T cells
CD19 marker
-B lymphocytes
CD28 marker
-helper T cells
CD3 marker
-helper T cells
CD16 marker
-natural killer cells
CD14 marker
-macrophages
G6PD (MOA and inciting drugs)
- glucose-6-phosphatate dehydrogenase important enzyme in hexose monophosphate shunt
- reduces NADP+ to NADPH, which in turn reduces GSSG to glutathione–> glutathione protects RBC’s against oxidative stress
- deficiency results in hemolytic anemia
- common in AA and mediterranean descent
- primaquine, chloroquine, sulfa, Isoniozid
paroxysmal nocturnal hemoglobinuria (genetic defect, MOA)
- defect in PIG-A gene which produces GPI anchors
- GPI anchors are necessary to attach complement inhibiting proteins, without which, complement chronically lyses RBCs
- occurs throughout the day, most concentrated urine in AM
blood smear of macrocytic anemia
- hypersegmented neutrophils
- can distinguish folate from B12 by neuro symptoms (only in B12) and increased MMA (only in B12)
SCID (enzyme deficiency… MOA… tx)
- adenosine deaminase deficiency
- inability to breakdown purines, buildup of deoxyadenosine triphosphate, which prevents synthesis of other nucleotides
- toxic to rapidly growing cells such as immune cells
- tx: bone marrow transplant
CML (genetics… MOA.. tx)
- t(9;22), philly chromosome, creates BCR-ABL fusion protein, constitutively active tyrosine kinase
- tx: TKI, imatinib (gleevec)
dacryocytes (tear drop cells on smear)
-indication of extramedullary hematopoeisis
von Willebrands (what is it, what does it do, lab values, inheritance)
- 2 jobs: protect factor 8 and adhesion of platelets to collagen via glycoproteins
- increased bleeding time and partial thrombosplatin time
- NL prothrombin time and NL platelets
- autosomal dominant
protein C
-inactivation of factors V and VIII, deficiency leads to prothrombotic state
DIC (common causes… 2 fold mechanism… lab values… diagnostic test…)
- sepsis or trauma, but most commonly obstetric complications
- activation of BOTH coagulation cascade and fibrinolytic system, leading to…
- increased bleeding time, PT and PTT
- fibrin split products (D-dimer)
Burkitt’s Lymphoma (genetics, path, common symptom)
- t(8;14) resulting in overexpression of c-myc
- starry sky, field of lymphocytes interrupted by occasional macrophages
- mass in jaw, and assoc. with EBV
Folate deficiency (physiologic role of folate… what deficiency looks like, who gets it, time course)
- tetrahydrafolate is important in one carbon transfers, crucial for purine synthesis
- deficiency leads to megaloblastic microcytic anemia without neurological symptoms
- folate stores deplete quickly (time course of months rather than years in B12)
- *NL MMA**
taut vs relaxed hemoglobin
- taut, tight, low oxygen, release oxygen, low affinity
- relaxed, lots of oxygen, pick it up and hold onto it, high affinity
SLL/CLL vs diffuse large B-cell lymphoma (Path smear and pathogenicity)
- small, still mostly circular lymphocytes on smear
- Richter’s is a transformation from SLL/CLL to diffuse large cell (about 10% of SLL/CLL) and a smear shows a distinct line of transformation
- 4-5x larger cells and more disorganized morphology
most common cause of hypercoaguable state (and 1 uncommon cause and 3 rare cases)
- factor V leiden
- prothrombin gene mutation
- protein s deficiency
- protein c deficiency
- antithrombin III deficiency
CLL (path smear)
- clonal expansion of b-lymphocytes arrested in development somewhere between pre-b cell and mature b cell
- results in smudge cells as b cells are not fully mature and break apart during preparation
HIT
- heparin induced thrombocytopenia
- antibodies form against heparin/platelet complex, activates platelets, they all quickly get used up forming lots of clots
- more likely in people who have been heparinized before
1 unit of raises hematocrit by….
-3%
thrombotic thrombocytopenic purpura (TTP)
- deficient vonWillebrand factor, leads to continual activation of platelets, destroys RBCs, leads to renal insufficiency
- this damage can lead to renal insufficiency and elevated creatinine
- NL PT and PTT, clotting factors are OK
vitamin K in clotting cascade
- vitamin K assits in carboxylating several clotting factors
- warfarin interferes with this action
acute onset cardiac friction rub is an indication of….
-uremia, get them some dialysis pronto
contraindicated for warfarin
-pregnant women
hemophagocytic lymphohistiocytosis (HLH)
- constitutional symptoms
- bone marrow aspirate reveals RBC’s engulfed in macrophages
multiple myeloma (CRAB)
- hypoCalcemia
- Renal insufficiency
- Anemia
- Bone lesions
hairy cell leukemia (negative symptoms, smear, diagnostic test)
- neg for night sweats and fever
- 4x more common in men, fatigue, fullness, weight loss
- “hairy cell” on smear
- TRAP (tartrate resistant acid phosphatase) positive… trap the hairy animal
fanconi’s anemia (what is it, why does it happen, what does it cause)
- most common congenital aplastic anemia and important cause of myeloid leukemia in kids
- defect in DNA repair
- bifid thumbs, renal dysgenesis, hypogonadism, microcephaly, high fetal hemoglobin
carboxylation of glutamic acid residues
-role of vitamin K in coag cascade
hemorrhagic disease of the newborn (what causes it, what prevents it)
- usually 2-7 days after birth, due to deficiency of vitamin K
- lacking intestinal flora that makes vitamin K
- every newborn in HOSPITAL gets vit K intramuscularly after birth
schilling test
-radiolabled B12–> in NL individuals, absorbed and excreted in urine, so we look for radiolabled B12 in urine, if not there, its not being absorbed (due to lack of intrinsic factor (produced by parietal cells) )
TTP-HUS (thrombotic thrombocytopenic purpura and hemolytic uremic syndrome)
- a subtype of MAHA (microangiopathic hemolitic anemia) often idiopathic, sometimes caused by certain drugs bacterial toxins (shiga toxin from E. coli)
- trifecta of hemolytic anemia, thrombocytopenia and platelet aggregation
- tx is generally supportive, keeping an eye on fluids, maybe dialysis
hemophilia A and B (which cofactors are affected, genetics)
- hemophilia A: factor 8
- hemophilia B: factor 9
- both are X-linked recessive
PT and PTT measure which cofactors…
- PT: 7… also 10, 5, prothrombin and fibrinogen
- PTT: 8, 9, 11, 12… also 10, 5, prothrombin and fibrinogen
hereditary spherocytosis (presentation (triad of symptoms), defect, and tx)
- anemia, splenomegaly, jaundice
- defect in RBC anchoring proteins: ankyrin, spectrin, band 3
- tx: splenectomy to cure anemia, sphereocytes persist
genetic abnormality in sickle cell disease (HbS)
-substitution of valine for glutamic acid at 6th position
henoch-schonlein (presentation, and serious complication)
- young boys, palpable purpuric lesions on buttocks and legs, joint pain, fever, malaise
- acute renal failure w/hematuria and proteinuria
post splenectomy, pts are at risk for… (4 pathogens with common trait..bonus, what will you see on smear?)
- encapsulated organisms: neisseria meningitides, strep pneumo, h. influenza, klebsiella pneumo
- given prophylactic vaccinations
- howell-jolly bodies, irregular RBCs, and target cells
bronze diabetes…
- jaundice and diabetes
- hemochromatosis… leads to end organ damage
lymphocyte rich hodgkins lymphoma (smear, epidemiology, prognosis)
- few RS cells (binucleate with inclusion-like nucleoli
- usually young males
- decent prognosis
mixed cellularity hodgkins (smear, epidemiology, prognosis)
- many RS cells, many lymphocytes (mixed ratio)
- generally presents in older pts
- poor prognosis
plummer-vinson disease (triad)
- esophageal-cervical web
- iron deficiency anemia (microcytic hypochromic)
- glossitis
- MOA: dysphagia due to web and glossitis prevent proper intake, results in iron deficiency anemia
scurvy… (vitamin deficiency, symptoms and pathophys)
- deficient in vit C
- important in hydroxylating valine and leucine allowing for crosslinks which add structural integrity to collagen
- bleeding gums, poor wound healing etc
sickle cell trait… (common SE)
- much less severe than sickle cell disease, can see some more serious complications at altitude
- episodic hematuria and polyuria as renal tubules are damaged over time and body is unable to concentrate urine
