heme Flashcards
(103 cards)
1
Q
Fetal erythropoiesis
A
Fetal Erythropoiesis occurs in : Yolk sac (3-8 weeks) Liver (6 weeks to birth) Spleen (10-28 weeks) Bone marrow (18 weeks to adults)
Young liver synthesizes Blood
2
Q
Hemoglobin development
A
Embryonic globins (zeta and epsilon) Fetal hemoglobin (HbF)= a2y2 Adult hemoglobin (HbA2)= a2B2 Adult hemoglobin (HbA2)= a2d2 (rare) HbF has a higher affinity for O2 due to less avid binding of 2-3BPG (2-3 BPG tells hemoglobin to release O2), so having less 2-3BPG makes fetal Hgb hold on to O2 more
At birth Hgb is about 50/50 HbF and HbA
3
Q
ABO and Rh classification
A
A group has the Anti B antibody (IgM) to B Ag, has the A antigen on it
B group has the Anti A antibody (IgM)
AB group has no antibodies
O group has both antibodies, and they are in IgM and IgG
Rh classification
+ (has the Ag)
Rh - no Ag, so has Anti D antibody (an IgG) (give moms IgG during and after each pregnancy)
4
Q
Hemolytic disease of the newborn AKA erythroblastosis fetalis
A
An Rh - mom with an Rh+ baby
First pregnancy: mom exposed to fetal blood (dutring delivery)-> formation of maternal anti-D IgG. Subsequent pregnancy- antiD IgG crosses the placenta and attacks the Fetal RBCs–> hemolysis in the fetus. Hydrops fetalis, jaundice, kernicterius. Prevent by administrating antiD IgG to Rh - moms during third trimenster and peripartum if fetus turns our +. Prevents maternal anti-D IgG production
ABO hemolytic disease of the newborn- Type O mom type A or B fetus, pre exisiting maternal anti-A or anti B cross IgG antibodies cross placenta–> hemolysis in the fetus. Mild jaundice in the neonate in 24 hours, can occur in the first born, Treatment: phototherapy or exchange transfusion
5
Q
Hematopoiesis
A
Multipotent stem cell
Myeloid stem cell: Erythroblasts, megakaryocytes, Granulocytes (Eosinophils, Basophils, Bands->PMNs), Monocytes–> Macrophage
Lymphoid cells–> B cells, T cells (Th cells, T cytotoxic ) NK cells
6
Q
Neutrophils
A
Acute inflammatory response cells. Numbers increase in bacterial infections Phagocytic. Multilobed nucleus Specific granules contain leukocyte alk phos, collagenase, lysozyme, and lactoferrin
Azurophilic granules (lysosomes) contain proteinases, acid phosphastase, myeloperoxidase, B- glucurondase
increased bands= CML or bacterial infections
chemotactics: c5a, IL8 LtB4, bacterial products, kallikirein, platelet activating facotr
7
Q
RBCs
A
Lifespan 120 days
Source of energy is glucose (90% used in glycolysis, 10% used in HMP shunt)
Membranes contain CL/HCO3- antiporter, which allow RBCs to export HCO3 and transport CO2 from the periphery to the lungs for elimination
Anisocytosis- varying sizes
Poikilocytosis = varying shapes
Blue color= RNA
8
Q
Thrombocytes
A
lifespan 8-10 days
When activated by endothelial injury, aggregate with other platelets and interact with fibrinogen to form platelt plug
Contain dense granules (Ca++, ADP, Serotonin, Histamine CASH) and a granules (vWF, Fibrinogen, fibronectin, platelt factor 4)
Approximately 1/2 of platet pool is stored in the spleen
9
Q
Macrophages
A
Long life in tissues, differentiate from monocytes
Activated by y-inferon
APCs MHC2
Important cellular component of granulomas
CD14 receptor is what initiates septic shock
10
Q
Eosinophils
A
Defend against helminths via MBPs
Bilobed nucleus, Packed with large eosinophilic granules of uniform size
produse histaminases, MBP, eosinophil peroxidase, eosinophil cationic protein
PACCMAN causes of eosinophilia Parasites Asthma Eosinophilic granulomatosis with polyaniitis (churg Strauss syndrome) Chronic adrenal insufficiency Myeloproliferative disorders Allergic processes Neoplasia (hodgkin lymphoma)
11
Q
Basophils
A
Mediate allergic reaction
Densely basophilic granuls
CML
12
Q
Mast cells
A
Can bind the Fc portion of IgE to membrane
Activated by tissue trauma, C3a and C5a, Surface IgE (cross linking by Ag)
release of histamine, heparin, tryptase, and eosinophil chemotactic factors
Involved in type 1 HS reactions, cromolyn sodium prevents mast cell degranulation, used for asthma prophylaxis
Vancomycin, opioids and radiocontrast dye elicit IgE independent mast cell degranulation
13
Q
Natural killer cells
A
important in innate immunity, especially against intracellular pathogens, larger than B and T cells, with distinctive cytoplasmic lytic granules (containing perforin and granzyme) act on target cells to induce apoptosis
Contain CD56, and CD16
14
Q
B cells
A
Follicles of lymph nodes, white pulp of spleen, unencapsulated lymphoid tissue
Contain Cd19, Cd20 and CD 21
15
Q
T cells
A
CD3
CD28 necessary for T cells (Treg, CD4 and CD8)
16
Q
Plasma cells
A
Large amounts of antibody
Clock face chromatin distribution with nucleas off to the side, RER and Golgi for secratory white part next to nucleus
mostly found in the bone marrow
Multiple myeloma is a plasma cell dyscrasia
17
Q
Primary hemostasis
A
Formation of a platelet plug (endothelial cells contain in the Wieble Palade bodies- vWF and Pselectin with factor 8) they also contain thromboplastin and tPA and PGI2
- Injury to the endothelium–> transient vasoconstriction via neural stimulation reflex and endothelin (from damaged cell)
- Exposure: vWf binds to exposed collagen
- Adhesion: platlets bind vWF bia Gp1b receptor at site of injury–> platelets undergo confirmational change–> Platelets release ADP(allows for exposure of Gp2b3a), TXA2 ( via COX chemotactic for platelets) and Ca+ (needed for coagulation cascade)
- Activation ADP binding to P2Y12 receptor induces Gp2b/3a expression on platelet surface
- Aggregation: Fibrinogen binds Gp2b3a receptos and links platelets
18
Q
Pro vs anti aggregation factors
A
PRO coag: TXA2 (released by platelets), decreased blood flow, increased platelet aggregation
Anti coag: PgI2, NO (from endothelial cell) increased blood flow, decreased platelet aggregation
Temporary plug stop bleeding, unstableunstable and easily dislodged–> coag cascade is secondary
19
Q
Thrombogenesis
A
formation of insoluble fibrin mesh
ASA irreversibly inhibits COX 1 and 2, thereby inhibiting TXA2 synthesis (no chemotactic)
Clopidorgrel, prasugrel, ticlodipine inhibit ADP induced expression of Gp2b 3a by irreversible blocking of the P2y12 receptor
Abciximab, Eptifibatide, and tirofiban inhibit Gp2b3a (so no fibrinogen binding, FIB or CIX)
Ristocetin is an assay activates vWF to bind Gp1b, failure of aggregation with ristocetin occurs in vWdisease, and Bernard Soulier syndrome
vWF carries/protects factor 8
20
Q
Bernard soulier syndrome
A
deficiency in Gp1b receptor (no VwF ability to bind)
21
Q
Kinin cascade
A
Kaikrein activates bradykinin
increases vasodilation, increase permeability, increase in pain
22
Q
Intrinsic pathway
A
12-12a, 11-11a, 9-9a
vWF activates 8– 8a
then 10- 10a
C1 esterase inhibits kalikrein and 12 and 11
C1 esterase inhbitiro dificeincy - hereditary angioedema
23
Q
Extrinsic path
A
7-7a
Tissue factor activates factor 10
24
Q
Combined pathway
A
10- 10a via extrinsic and intrinsic path
5a-2-2a (thrombin)
2a- 1 -1a (fibrinogen)- fibrin monomers stabiliizes fibrin between platelets
25
Fibrinolytic system
tissue Plasminogen activator activates Plasmin which degrades fibrin (D-dimer)
26
Vitamin K
Factors 2, 7 9 and 10 C and S
Epoxide reductase activates Vitamin K which yCarboxylates 2 7 9 10 C S
Warfarin and liver failure inhibits the epoxide reductase
Factor 7 has the shortes half life, factor 2 has the longest
27
Antithrombin
inhibits thrombin factor 2a and factors 7 9 10
heparin induces antithrombin (inhbitition of factor 2 and 10)
28
Factor 5 leidin
produces factor 5 that is resistent to inhibition by activated protein C
29
Microcytic anemia
hemoglobin issues (TAIL)
Defective globin production: Thalessemias
Defective heme synthesis: Anemia of chronic disease, iron deficiency (late), Lead poisoning
30
Reticulocyte index
the corrected reticulocyte count
reticulocyte percent x actual Hct/normal Hct (45%)
31
Iron deficiency anemia
low iron due to chronic bleeding (GI loss, menorrhagia), malnutrition, absorption disorders, GI surgery, or increased demand (pregnancy) decreased final step in heme synthesis (Ferrochelatase cant add iron to protoporphyrin in the mitochondira)
labs: decreased iron, increased TIBC, decreased ferritin (stores), increesed free erythrocyte protoporphyrin, increased RDW ( you have some small and some normal size), decreased Index
Symptoms: fatigue, pallor, pica, spoon nails
low hemoglobin->low myoglobin
May manifest as glottitis, cheilosis, Plummer vinson syndrome (triad of iron deficiency anemia, esophageal webs and dysphagia- you dont eat steak bc of webs, then low iron)
32
Iron transport
iron is consumed, absorption occurs in duodenum via DMT1 transporters, the heme form is more readily absorbed from animals
Enterocytes transport the iron across the cell membrane into blood via ferroportin
Transferrin transports the iron in the blood and delivers it to liver and bone marrow for macrophage storage
Storred intracellular iron is bound to ferritin, preventing iron from producing free radicals
Serum iron is iron in the blood
TIBC- measure of transferrin (when iron stores are depleted- you send out more scavengers)
percent saturation- normal=33%
Serum ferritin- reflects iron stores in macrophages and the liver
33
alpha thalessemia
a-globin gene deletion, there are 4 alpha genes on chromosome 16--> decreased alpha globin synethesis. cis deletio (same chromosome, happens in asians)
Trans on different chromosomes (pravelent in africans
normal is aa/aa
aa/a- athal minor, no anemia
a-/a- (trans) , or aa/- - (cis) a thal minor, mild microcytic, hypochromic anemia, cis deletion my worsen outcome for carriers offspring)
a-/ - - hemoglobin H disease (HbH) ecess B globin, forms tetraterms, moderate to severe microcytic hypochromic anemia
- -/ - - (hemoglobin barts disease, excess y globin gene, hedrops fetalis
34
B-thalassemia
Point mutations in splice sites and promoter sequences on chromosome 11--> B globin synthesis
Pravelent in meditteraneans
B-thal minor (heterozygote): b chain is underproduced, usually asymptomatic, diagnosed by increased Hgb A2 on electrophoresis
Major (homozygoete- B chain is absent, severe microcytic hypochromic anemia with target cells and increased anisopoikilocytosis (increased RDW) require blood transfusion -- 2' hemochromatosis), marrow expansion (crew cut on x ray, skeletal deformaties, chipmunk facies, extramedularry hepatopoiesis--> hepatosplenomagaly
increased risk of parvovirus
HbS/B thal heterozygote
35
Lead poisoning
lead inhibits ferrochelatase and ALAD--> decreased heme synthesis and increased RBC protoporphoryn, also inhibits rRNA degradation --> RBCs retain aggregates of rRNA (basophilic stippling), encephalopathy and erythrocyte basophiling abdominal colic and sideroblastic anemia, drops, wrist and foot drop
Dimercaprol and EDTA are 1st line of treatment
Succicmer used for chelation in kids
Lead lines on gingivae and on metaphysis of long bones
36
Sideroblastic anemia
genetic(X linked) defect in ALAS, acquired (myelodysplastic syndromes, and reversible alcohol is the most common lead poisoning, vitamin B6 deficiency, copper deficiency , drugs, linezolid isoniazid
Labs will show: increased iron, normal/low TIBC, increased ferritin, ringed sideroblasts, basophilic stippling of RBCs,
Treatment: pyridoxine (B6 cofactor for ALAS)
37
MEgaloblastic anemia
Impaired DNA synthesis--> malnutrition of nucleus of precursor cells in bone marrow delayer relatice to maturation of cytoplasm
Causes: vitB12 deficiency, folate deficiency, meds (hydroxyurea, phenytoin, methotrexate, sulfa drugs
RBC macrocytosis, hypersegmented neutrophils
38
Folate deficiency
causes: malnutrition (alcoholic), malabsorption, drugs (methotrexate, TMP phyenytoin) increased requirement (hemolytic anemia, pregnancy)
increased homocystein, normal methylmalonic acid--> no neuro symptoms (vs B12 deficiency
39
folate metabolism
Folate circulates in the serum as methyl-THF, you need to remove methyl group to have DNA synthesis
Vit B12 takes the methyl group, homocysteine takes the methyl group from B12-->methionin
To make homocysteine you need methylmalonic acid
40
Vit B12 deficiency
causes pernicious anemia, malabsorption (Crohns disease), pancreatic insufficiency gastrectomy, insufficient intake (vegans), Diphyllobothrium latum (fish tapeworm)
increased homocysteine (cant take the methyl group), increased methylmalonic acid
Neuro symptoms- reversible dementia, subacute combined degeneration (due to involvement of B12 in FA pathways and myelin synthesis)
Spinocerebellar tract, lateral corticospinal tract, dorsal column dysfunction
Folate supplementation when really a B12 deficiency can correct the anemia, but neuro symptoms worsen
Liver can store B12 for yearns
41
Orotic aciduria
Inability to convert orotic acid to UMP (denovo pyrimidine syntheis)
```
Autosomal recessive
Presents as failure to thrive, dev delay, and megaloblastic anemia refractory to folate and B12
No hyperammonemia (vs ornithine transcarbomylase deficiency where increased orotic acid with hyper ammonemia)
```
Give UMP or uridine triacetate to bypass mutated enzyme
Orotic acid will accumulate in urine
42
Non megaloblastic anemia
No issue with nucleus division so they are appropriately sized
Macrocytic anemia,
Causes- alcoholosm, liver disease
43
Diamond Blackfan anemia
congenital pure red cell aplasia, rapid onset within first yeat of life theres an intrinsic defect in erythrocyte progenitor cells
So your red cells are big
increased HgbF but decrease in total Hgb
Short stature, craniofacial abnormalities, upperextremity malformation( third phalanx on thumb
44
Normocytic normochromic anemia
either non hemolytic or hemolytic
the hemolytic anemia can be due to intrinsic (the red cell bursts by itself) or extrinsic (red cell is being sheared)
and by the location of hemolysis (intravascular vs extravascular)
hemolysis can lead to increases in LDH, reticulocytes, unconjugated bilirubin, pigmented gallstones, and urobilinogen in the urine
45
Intravascular hemolysis
decrease in haptoglobin (eats up the free hemoglobin), increase in schistocytes on blood smear, hemoglobinuria, hemosiderinuria, and urobilinogen in urin
mechanical hemolysis (prosthetic valve), paroxysmal nocturnal hemoglobinuria, microangiopathic hemolytic anemias
46
Extravascular hemolysis
macrophages in spleen clear RBCs, spherocytes (hereditary spherocytosis andautoimmun hemolytic anemia, no hemoglobinuria/hemosiderinuria, urobilinogen in urine
47
Anemia of chronic disease
inflammation (IL6- increased hepcidin (released by liver, binds to ferroportin on intestinal mucosal cells and macrophages, thus inhibiting iron transport--> decreased release of iron from macrophages and decreased iron absorption from the gut
chronic infections, neoplastic disorders, CKD, autoimmune diseases
low iron, low TIBC, increased ferritin (youre storing away you iron to divert from infection)
can eventually become microcytic
adress the underlying cause of inflammationcna give EPo
48
Aplastic anemia
caused by failure or destruction of hematopoietic stem cells due to: radiation and drugs (benzene, chloamphenicol, alkylating agents, antimetabolites)
Viral agents- EBV, HIV, hepatitis viruses
decreased reticulocyte count, EPO is increased
49
Fanconi anemia
AR DNA repair defect--> bone marrow failure, normocytosis or macrocytosis
idiopathic immune mediated
50
hereditary spherocytosis
autosomal dominant
defect in proteins interacting with RBC membrane (ankyrin, band 3, protein 4.2, spectrin)
Small round RBC with increased MCHC--> oremature removal by spleen
Splenomegaly, aplastic crisis
eosin 5 malerimide binding test, increased in fragility, normal to decreased MCV with abundant of RBcs
splenectomy treats it
51
G6pD deficiency
X-linked recessive, G6pd defect-->decreased NADPH--> decreased reduced glutathione--> increased RBC susceptibility to oxidative stress (sulfa drugs, antimalarials, fava beans--> hemolysis
Causes extravascular and intravascular
Back pain, hemoglobinuria a few days after a stress
Heinz bodies and bite cells
52
Pyruvates kindase deficiency
AR
Pyruvate kinase defect--> decreased ATP--> rigid RBCs--> extravascular hemolysis
Increases levels of 23 bpg-- decreased hemoglobin affinity O2
hemolytic anemia in newborns
53
Paroxysmal nocturnal hemoglobinuria
CD34+ hematopoietic stem cell mutation -- increased complement mediated intravascular hemolysis, especially at night (acidosis)
Acquired PIGA mutation--> impaired GPI anchor sythesis for decay accelaratingfacotr and membrane in
Red cells protect themselves from complement By having DAF and MIRL (decay accelerating factor, CD55) DAF and Mirl are attached via GPI (glycosylphosphatidyl inositol)
When GPI is mutated- DAF and MIRL float away rendering the RBC susceptible to complement- especially when complement gets activated during acidosis
RBCs WBC and platelets are lysed, intravascualr hemolysis leads to hemoglobinemia and uria, and hemosiderinuria, main cause of death is thrombosis of hepatic , portal, or cerebral veins (from lysed platelets)
Complications include iron deficiency anemia (hemoglobinuria, and AML
54
Sickle cells disease
Autosplenectomy- HJ bodies-- increased risk of infection
S pneumonia
Salmonella osteomyelitis
Painful dactylitis (sweiiling of distal joints, priapism, acute chest syndrom, sickling in renal medulla --> hematuria
Treatment is hydroxyurea--> increase HbF and hydration
55
HbC
glutamic acid to lyCine mutation in B globin
causes extravacular hemolyisi
HbSC (1 mutation of each have less disease)
Homozygotes- hemoglobin crystals inside RBC target cells
56
Autoimmune hemolytic anemia
a normocytic anemia that is usually idiopathic and coombs +
2 types
Warm AIHA-chronic anemia in which iGG causes RBC agglutination, seen in SLE and CLL and certain drugs (methyl dopa)
```
cold agglutination (acute anemia in which IgM and complement causes RBC agglutination upon exposure to cold, --> painful, blue fingers and toes
seen in CLL, mycoplasma pneumoniae infections, Mononucleosis
```
57
Direct coombs test
Anti- IgG antibody, added to pt RBC, anti-IgG bind the RBC IgG and cause agglutinatination
Indirect just measures if there are anitbodies by adding normal RBCs to serum (if there are Ab the cells willa gglutination
58
Microangiopathic hemolytic anemia
Shictocytes
Shearing due to intravascular hemolysis
Seen in TTP (Adamsts13 deficiency- vWF doesnt get cleaved) DIC, HUS (verotoxin binds endthelial cells) SLE HELLP syndrome and HTN
59
Macroangiopathic hemolytic anemia
prosthetic heart vavles aortic stenosis
60
Hemolytic anemia die to infection
increased destruction of RBCs (malaria, babesia)
61
Corticosteroid eosinopenia
Cause neutrophilia, despite causing eosinopenia and lymphopenia,
Corticosteroids cause decreased activation of neutrophil adhesion molecules, impairing migration out of the vasculature to sites of inflammation
Corticosteroids sequester eosinophils in lymph nodes and cause apoptosis of lymphocytes
62
Neutrophil left shift
increase in neutrophil precursors, band cells and metamyelocytes in peripheral blood
usually seen with neutrophilia in the acute response to infection or inflammation
Called leukoerythroblastic reaction when left shift is seen with immature RBCs
Severe anemia or marrow responce
63
Heme synthesis, porphyrias, and lead poisoning
Porphyrias are hereditary or acquired conditions of defective heme synthesis that lead to accumulation of heme precursors, lead inhibits specific enzymes (ferrochelatase and ALAd) leading ot similar conditions
64
Lead poisoning
Ferrochelatase and ALAD deficiency
```
Protoporphyrin and ALA accumulates
Microcytic anemia (basophilic stippling, ringed sideroblasts in bone marrow), GI and kidney disease
```
Kids- exposure to lead paint-> mental deterioration
Adults: batteries, ammunition--> headache, memory loss, demyelination (peripheral neuropathy)
65
Acute intermittent porphyria
prophobilinogen deaminase deficiency
(alos uroporphyringen 1 synthease
Autosomal dominant mutation
Porphobilinogen, ALA accumulates
Symptoms (painful abdomen, port wine colored pee, polyneuropathy, psychological disturbances, precipitated by drugs (cyp 450 inducers, alcohol, starvation)
Treatment- hemin and glucose
66
Porphyria cutanea tarda
Uroporphyrinogen decarboxylase deficiency
Uroporphyrin accurmulates (tea colored urine)
blistering cutaneous photosensitivity and hyperpigmentation
Most common porphyria, exacerbated with alcohol consumption
Causes- familial, hepatitis C
treat with phlebotomy, sun avoidance, antimalarials (hydroxychloroquine)
67
Heme synthesis
Glycine, succinyl CoA and B6 make ALA (via ALAS RLS, deficiency causes sideroblastic anemia X linked)
ALA-> Porphobilinogen ( ALAD, lead poisoning)
Porphobilinogen-> Hydroxymethyblane (Porphobilinogen deaminase, Acute intermittent porphyria)
Uro-> copro porphynogen 3 (Uro de carboxylase (porphyria cutanea tarda Tea colored urine)
in mito, ferrochelatase and iton and protoporphyrin--> heme
68
iron poisoning
cell death from free radicals and peroxidation of membrane lipids
Abdominal pain, vomiting, GI bleeding--> metabolic acidosis with anion gap, and organ damage, leads to carring with GI obstruction
Chelate with deferoxamine, deferasirox, gastric lavage
Chronic hemochromatosis (arthropathy, cirrhosis, cardiomyopathy, diabetes mellitus and skin pigmentations, hypogonadism, phlebotomy or chelations
69
Hemophilia A B or C
elevated pTT
C can be autosomal
Hemarthrosis (bleeding into joints, knee easy bruising,, bleeding after trauma or surgery
Treatment: desmopressin and specific factor
70
Bernard Soulier syndrome
decreased Gp1b, no platelet to vWF adhesion
| Labs: abnormal ristocetin test, large platelets
71
Glanzmann thrombasthenia
Defect in aggregation
Decreased Gp2b3a, blood smear shows no platelet clumping
72
Immune thrombocytopenia
destruction of platelet in spleen, Anti-Gp2b3a antibodies--> splenic macrophages phagocytose platelets
idiopathic or autoimmune disorders
Labs: increased megakaryocytes in BM, decreased platelet count
Treatment: steroids, IVIG to give something to spleen to heat
73
TTP (thrombotic thrombocytopenic purpura
inhibition of ADAMTS13 (a vWF metalloproteas) -> increase large vWF multimers--> increased platelet adhesion and aggregation
Triad of thrombocytopenia (platelets), MAHA (Hgb decreased, schistocytes, increased LDH), acute kidney injury (increased Cr)
Triad + fever and neuro symptoms
PT and PTT
Treatment: plasmapherisis, steroids, rituximab
74
HUS
shiga like toxin from EHEC O157H7 infection
| Bloody diarhea
75
vWF
tratment: desmopressin, which releases vWF stored in endothelium
76
DIC
Snake bites, Sepsis (gram negatives), Trauma, Ob compliation, acute pancreatitis, Malignancy, nephrotic syndrome, Transufion
increased Fibrin degradation products (D dimers, Fibrinogen decreased, decreased factors
77
Factor 5 leiden
Protein C active site is messed up
| DVT, cerbra vein thrombosis, recurrent pregnancy loss
78
prothrombin mutation gene
increasedprotduction of prothrombin-> plasma levels and bvenous clots
79
Leukemia vs Lymphoma
Leukemia- lympoid, myeloid neoplasma with involvement in bonemarror, tumor cells in peripheral blood
Lymphoma- discrete tumor mass in lymph nots
80
Hodgkins vs non hodgkin
Hodgkin: localized single group of nodes with contigupus spread, better prognosis
Reed sternberg cells with attraction of lymph cells
bimodal age distribution, associated with EBV
Non-hodgkin: multiple lymph nodes involved, extranodal involvment common, worse prognosis, B cells or T cells, can occur in kids and adults, HIV and EBV, HTLV
81
Hodgkin lymphoma
Reed sternberg cells
CD15+ and CD30+ of B cell origin
2 owl eyesx 15 =30
Nodular sclerosis- most common
lymphocyte rich- best prognosis
mixed- eosinophilia- immunocomp patients
lymphocyte depleted
82
Burkitt lymphoma
t18, 14 translocation of c-myc (8) to heavy chain Ig (14)
Starry sku, sheets of lymph cells with interspersed tingible body macrophages, associated with EBV
Jaw lesion in africa, pelivc or abdomen in sporadic form
83
Diffuse large B cell lymphoma
Usually older adults
mutation in BCL2, BCL6 most common
84
Follicular lymphoma
Addults
t(14, 18)
18 has BCL2, 14 is ig heavy chain
wax and waning lymphadenopathy
85
Mantle cell lymphoma
Males, CD5+ (usually on T cells)
t(11,14) cyclin D on 11 and heavy chain (allows cell to go G-> S phase)
Very aggressive, patients present late
86
marginal zone lymphoma
t (11, 18) chronic inflammation, Sjogrens syndrome, chronic gastritis (MALToma)
87
Primary central nervous system
EBV related associated with HIV and AIDS
often a single, ring enhancing lesion on MRI should be distinguised from toxoplasmosis via CSF
88
Adult T cell lymphoma
Caused HTLV associated with IV drug abuse
Adults with cutaneous lesions, common in japan (T cell Tokyo,
Lytic bone lesions, hypercalcemia
89
Mycosis fungoides/ Sezary syndrome
Skin patches and plaques (cut T cell lymphoma) characterized by atypical CD4 cells with cerebriform neuclei and intradermal neoplastic cell aggregates (Pautrier microabcess) may prgress to sezary syndrome (t cell leukemia)
90
Plasma cell dyscrasia
characterized by monoclonal immunoglobulin (iG) ovverproduction due to plasma cell disordr
SPEP or free light chain with M spike (overproduction of a monoclonal IgG fragment
91
Multiple myeloma
```
characterized by
Overproduction of IgG or sometimes IgA
Clinical features: CRAB (for cancer)
hyperCalcemia
Renal involvement
Anemia
Bone lytic lesions (punched out on X ray)--> Back pain
```
Peripheral smear shows rouleaux formation (increased protein messes up charge--> RBC stacked)
Urinalysis shows Ig Light chains (Bence jones proteinuria with - urine dipstick
monoclonal Bone marrow, intracytoplasmic inclusions containing igG
Complication: increased risk of infection, 1' amyloidosis (ALight chian)
92
Waldenstrom macroglobinemia
Over production of IgM (macroglobinemia because igN is the largest Ig)
Clinical features: peripheral neuropathy, no CRAB findings, hyperviscosity syndrome (Headache, Blurry vision, Raynaud phenomenon, Retinal hemorrhages)
Bone marrow analysis - small lymphocytes with IgM containing vacuoules
Lymphoplasmacytic lymphoma
Complications: thrombosis
93
Monoclonol gammopathy of undetermined significance
over production of any Ig type, usually asymptomatic. No CRAB findings,
1-2% risk per year of transitioning to multiple myeloma
94
Myelodysplastic syndromes
Stem cell disorders involving ineffective hematopoiesis--> defects in cell maturation of non lymphoid lineages
Caused by denovo mutations or environmental exposure (radiation, benzene, chemotherapy)
Risk of transformation to AML
Pseudo Pelger Huet anomaly- neutrophils with dilobed (duet nuclei, typically seen after chemo)
95
Leukemias-
unregulated growth and differentiation of WBCs in bone marrow--> marrow failure-> anemia, infections, and hemorrhage
increased fucked up WBC in blood,
Leukemic cell infiltration of liver, spleen, lymph nodes and skin (leukemia cutis possible)
96
Acute lymphoblastic leukemia/lymphoma
usually in kids, Tcell ALL can present with mediastinal mass (SVC-like syndrome)
Associated with down syndrome
Peripheral blood and marrow have an increase in lymphoblasts
TdT+ (marker of pre-T and pre B cell, CD 10 + )marker of pre B cells)
Most responsive to therapy
May spread to CNS and testes
t 12,21--> better brognosis
97
Chronic lymphocytic leukemia/ small lymphocytic lymphoma
Older, Most common adult leukemia
CD20+ , CD23+, CD 5+ B cell neoplasms
Often asymptomatic, progresses slowly, smudge cells in peripheral smear, autoimmune hemolytic anemia
CLL= Crushed Little lymphocytes (smudge cells)
Richter transformation CLL SLL
98
Hairy cell leukemia
Adult males Mature B cell tumor, Cells have hair projections, peripheral lymphadenopathy is uncommon
Causes marrow fibrosis (dry ttrap on aspirtation
associated with BRAF
Treatment: Cladribine, pentostatin
99
Acute myelogenous leukemia
```
Auer rods (MPO condensates)
usually acute promyelocytic --> increased circulating myeloblasts on peripheral smear
```
Risk factors: alkylating chemotherapy, radiation, myeloproliferative disorders, Down syndrom
APL (t15 17) responds to all trans retinoic acid vit A
100
CML
Philidelphia chromosome, t 9 22 (BCR-ABL)
Mature and matureing granulocutes
very low Alk Phos (cells not appropriate)
Responds to BCR-ABL tyrosine kinase inhbitiors (Imatinib)
101
Chronic myeloproliferative
malignant hematopoietic neoplasms with varying impacts on WBCs and myeloid cell lines
Polycythemia vera (acquired JAK2 mutation)- may present as intense itching after shower, svere burning pain, decreased EPO. Treatment is phelbotomy, hydroxyurea, ruxlininiv (JAK 1/2 inhbitor)
Essential thrombocythemia: characterized by massive proliferation of megakaryocytes, bleeding and thrombosis,
Myelofibrosis: Obliteation of bone marrow with fibrosis (increased fibroblast activity, associated with massive splenomegaly and teardrop,
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LANGERHANS CELL histiocytosis
Collective group of proliferative disorders
Presents un a child as lytic bone lesions and skin rash or as a recuttent otitis media witha mass in the mastoid
Cells are immature and dont activate T cells
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Cells express S100 mesodermal origin and CD1a
Bierbech franules (tennis rackets or rod shaped on EM
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Tumor lysis syndrome
Oncologic emergency
Release of K and PO4--
Ca++ gets sequesterd by PO4---
Increased nucleic acid breakdown--> hyperuricemia--> AKI
Prevention via aggressive hydration, allopurinol, rasburicase
