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Heme exam #1
terms and concepts for DMU heme exam #1
164
Medical
10/20/2012

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Term
Hematopoiesis
Definition

Formation of blood cells

provides the cellular elements (RBCs and leukocytes) of the peripheral blood

takes place in the bone marrow

delivery of oxygen to the tissues and host cell defense

replaces 0.5 X 10^12 cell/day

Term
Lymphocyte life span
Definition
years
Term
RBC lifespan
Definition
120 days
Term
platelet life span
Definition
7 to 10 days
Term
Granulocyte life span
Definition
6 to 8 hours
Term
Hematopoietic stem cells
Definition

Give rise to progenitor cells of all lineages

highest proliferative potential of any hematopoietic cell type

can't be identified morphologically

Term
Bone marrow stromal cells
Definition

Impotant role in maintenance and differentiation of hematopoietic cells

examples: adipocytes, fibroblastoid cells and reticuloendothelial cells

stem cells/primitive precursors bind firmly

maturing precursor cells are nonadherent

differential expression of cell adhesion molecules regulates the binding activity

Term
Cytokines
Definition

Drive specific cell differentiation pathways

progenitor cell cytokines act on immature cells

end-stage cytokines act on more differentiated cell types to induce lineage-specific differentiation

Term
Granulocyte colony stimulating factor
Definition

Released by macrophages at inflammatory sites

circulates to bone marrow to cause the production and release of neutrophils

makes granulocytes in the bone marrow

Term
EPO
Definition

produced/released by peritubular interstitial cells (kidney) in response to hypoxia

circulates to bone marrow to cause the production/release of RBCs

elevated oxygen pressure inhibits production of EPO

Term
TGF-beta
Definition

inhibitory cytokine

downregulation of stem cell growth/differentiation

Term
Yellow bone marrow
Definition
normally inactive bone marrow and mainly adipose tissue
Term
Red bone marrow
Definition

Bone marrow active in hematopoeisis

 

Term
Extramedullary hematopoiesis
Definition
takes place in the spleen and liver when bone marrow is dysfunctional or unable to meet the demands on it
Term
Erythropoiesis
Definition

the formation or production of RBCs

starts: primitive RBCs in the embryonic yolk sac

continues: extramedullary organs (liver, spleen)

predominates in the red marrow during late fetal development

Term
Granulopoiesis
Definition

Production of cells in the granulocytic lineage, including neutrophils, eosinophils and basophils

after release, circulate for a few hours then die

Splenic macrophages remove dead granulocytes from circulation

increased % of band forms in the blood termed "shift to the left" = infection

Term
Monocytes-macrophages
Definition

macrophages develop from monocytes and are distributed throughout the body

monocytes circulate for approximately 8 hours, then enter the tissues to differentiate into macrophages

macrophage lifespan - months to years

Term
Histiocytes
Definition
macrophage of the loose connective tissue
Term
Kupffer cells
Definition
macrophage of the liver
Term
Osteoclast
Definition
macrophage of the bone
Term
Microglial cell
Definition
macrophage of the nervous system
Term
Lymphopoiesis
Definition

Production of cells in lymphocytic lineage, including T lymphocytes, B lymphocytes or NK cells

B lymphocytes and NK cells develop entirely in the bone marrow and are release into the peripheral blood

Term
T lymphocyte maturation sequence
Definition

mature in the bone marrow until prothymocytes are released into peripheral blood to migrate to the thymus

Once in thymus, termed thymocytes

thymocytes matue/differentiate into T lymphocyte subsets

most thymocytes die in the thymus

once T lymphocytes leave the thymus, most populate lymphatic organs

Term
Thrombopoiesis
Definition

production of platelets (thrombocytes)

role in hemostasis - limit bleeding, repair endothelium

stimulated by thrombopoietin

Term
Megakaryocytes
Definition

Long cytoplasmic extensions which constrict at various points and divide into fragments

each one = 100 - 1000 platelets

Term
Platelets
Definition

2-4 micrometers in size and anuclear

lifespan - 9 days

death - phagocytized in liver or spleen

emergency reserve in the spleen

Term
Bone marrow changes throughout life
Definition

 

 

First few years of life → all marrow is red

 

By age 18, red marrow is found in ribs, sternum and pelvis

 

 

Term
RBC maturation
Definition

lose nuclei before entering circulation

mRNA disappears 1-2 days after release

No protein synthesis - can't replace damaged molecules

Term
End of RBC life
Definition

old, ineslastic RBCs are trapped in the spleen and phagocytosed by macrophages (bilirubin produced)

 

Term
Extravascular hemolysis
Definition

RBCs lose flexibility and are destroyed in the spleen

Release of bilirubin from RBCs

Splenomegaly

possible jaundice

Term
Intravascular hemolysis
Definition

RBCs are damaged while circulating through the body

RBC components in the blood (Hb)

Hemoglobinuria

Term
Hereditary spherocytosis
Definition
Spectrin mutation leads to rounded, short lived RBCs
Term
Purpose of RBC metabolism
Definition

Keeping iron rdueced (Fe2+)

Maintaining K+/Ca2+ gradients

Keeping protein SH-groups reduced

Maintaining cell shape

Term
When RBC metabolism fails....
Definition

Cells fill with calcium

cells release K+

Lose biconcave shape

Term
Spherocytic anemia
Definition

Problems with the RBC cytoskeleton

extravascular hemolysis

Term
Nonspherocytic anemia
Definition

metabolic, not cytoskeletal problems

both intra and extravascular hemolysis

Term
Energy clutch pathway
Definition
Glycolysis without the gain of ATP
Term
2,3 BPG
Definition

Production is decreased at low pH

Decreases the affinity of Hb for oxygen

Term
Glycolisis in RBCs
Definition

Not responsive to insulin

Very sensitive to pH - inhibited by acidic pH (less lactate)

Term
Pentose Phosphate Pathway
Definition

Provides reduction equivalents in the form of NADH

Low NADPH concentration activates glucose-6-phosphate dehydrogenase

Pentose products are re-indtroduced into glycolysis

Term
Glutathione
Definition

Protects RBCs from reactive oxygen species

 

 

 

Term
G6PD deficiency
Definition

Hemolytic anemia fom lack of NADPH

Most common RBC enzymatic defect (X-linked)

Lifespan of RBC is shortened because oxidative damage leads to loss of metabolic activity

Prevelant in African/Mediterrenean populations

Hemolytic crisis triggered by: infections, H2O2 producing drugs, fava beans

Splenomegaly, jaundice

Term
Pyruvate Kinase deficiency
Definition

Hemolytic anemia from lack of NADH/ATP

nonspherocytic hemolytic anemia without reactive oxygen induced crises

RBCs run out of ATP and degenerate prematurely

Splenomagaly, Jaundice

Term
RBC cytoskeletal defets
Definition

present as hereditary spherocytosis

Autosomal dominant

Most common: ankrin mutation

Less common: Band 3, spectrin, Protein 4.2 mutation

 

Term
Paroxysmal Nocturnal Hemoglobinuria
Definition

Form of intravascular hemolytic anemia

mutation in the PIGA gene

an example of somatic mosaicism

 

Term
THF
Definition

Function form of folate found in the body

formed from folate by dihydrofolate reductase

Term
Methotrexate
Definition

Inhibitor of dihydrofolate reductase

prevents generation of THF

antiproliferative effects

Term
N10 formyl THF
Definition
most oxidized form of THF
Term
N5 methyl THF
Definition

Most reduced form of THF

Form that most of the folate circulating in the blood is in

Term
Serine hydroxymethyltransferase
Definition

catalyzes the rxn providing the majority of the carbon for the one carbon pool

 

Serine  +  THF  -->  Glycine  +  N5, N10-methylene-THF + H2O

 

Term
Uptake of folate from the blood
Definition

Receptor mediated endocytosis

Receptors have high affinity for folate monogluamases (particularly N5-methyl THF monoglutamate which is the most abundant form in the circulation)

Inracellular folate is rapidly metabolized by the addition of polygluatame (mechanism of folate retention)

Term
Thymidlate synthase
Definition

Converts dUMP to dTMP

essential step in the synthesis of DNA

Most important rxn clinically

Term
Vitamin B12 (cobalamin)
Definition

only synthesized by certain bacteria

best dietary sources are liver, kidney, meats, dairy and shellfish

Term
Biologically active forms of cobalamin (B12)
Definition
Adenosylcobalamin and Methylcobalamin
Term
Intrinsic factor
Definition

Produced by the parietal cells of the stomach but is only active in the small intestine

Complexes with B12 so it can be taken up in the ileum

Term
Pernicious anemia
Definition

Lack of ability to absorb B12 from the ileum

autoimmune disease

No production of intrinsic factor

Term
Transcobalamin (TC)
Definition

Complexes with B12 in the portal blood

synthesized by the cells of the ileal mucosa

Required for B12 uptake from the blood

Term
Haptocorrin
Definition

Binds most of the B12 in circulation

complexes with B12 and is taken up by the liver

forms a circulating store of B12

Term
The Schilling test
Definition
Measures ability of patient to absorb 12
Term
Methylmalonyl-CoA mutase
Definition

Required for the metabolism of propionyl-CoA

Requireds adenosylcobalamin

Deficiency of B12 causes an accumulation of L-methylmonyl-CoA and hydrolysis of methylmalonic acid leading to organic acidemia

Term

Methionine synthase

 

Definition

converts homocysteine to methionine

has an absolute requirement for methylcobalamin

Term
Methyl trap hypothesis
Definition

Lack of B12 in the diet will cause a functional folate deficiency as the body's folate pool becomes trapped in the N5-methyl THF form

only the methionine synthase rxn can convert N5-methyl THF back to THF

 

Term
Neurologial consequences of B12 deficiency
Definition

Results in demylenation

likely caused by faulure of the methionine synthase rxn

Term
Functional folate deficiency
Definition

B12 deficiency

accumulation of N5-methyl THF

Thymidine synthesis is blocked and DNA synthesis is prevented

Term
Actual folate deficiency
Definition

Dietary insufficiency (not taking in enough folic acid)

Thymidine synthesis is blocked and DNA synthesis is prevented

Term
Megaloblastic anemia
Definition

Occurs in folate and B12 deficiency

block on DNA synthesis in the absence of other checks on growth will lead to an increase in cell size

Most apparent in rapidly-diving cells

Term
Folate needs increased by:
Definition

pregnancy

lactation

growth

chronic hemolytic anemia

Term
B12 needs increased by:
Definition

Pregnancy

periods of growth

Term
Properties of iron
Definition

very useful for binding oxygen and transferring electrons

must be in the bound form at all times - no free form

Term
Excretion of Iron
Definition

no regulated loss through urine

Blood loss - intravascular hemolysis, menstruation

Sloughing off of iron-containing cells in the intestines and kidney

Term
Distribution of iron in the body
Definition

80% in active forms - Hg, myoglobin, cytochromes, bound to transferrin

20% in inactive forms - dynamic storage in ferritin, degenerated long term storage in hemosiderin

Term
Transferrin
Definition
transfers iron in the plasma
Term
Ferritin
Definition
stores iron inside cells - liver, spleen, bone marrow
Term
Hepcidin
Definition

shuts down Ferroportin and is the master regulator of iron in the body – it is released from the liver in stress conditions – by temorarilly restricting the availablity of iron it inhibits the growth of microbial organisms that need the iron to grow

Also regulates the release of iron from macrophages

Mutation of HFE causes low expression

Term
Post-transcriptional regulation of ferritin translation
Definition

5' UTR contains a sequence that fuctions as an IRE

IRP binds to the IRE and blocks translation

If there is free iron in the cytoplasm, it binds to IRP and displaces displaces it from the mRNA (turning off the inhibition)

Translation begins quickly

Term
Serum iron determination
Definition

Test to diagnose iron poisoning or overload

limited diagnostic value since it provides no info about body iron stores

Term
Total iron binding capacity (TIBC)
Definition

Measures unoccupied transferrin

The higher the value the lower the iron stores

Term
Serum Ferritin test
Definition
best measure for body iron stores
Term
Red cell protoporphyrin test
Definition
The lower the iron stores, the higher the value
Term
Causes of iron deficiency
Definition

Chronic blood loss

Chronic disease (hepcidin production)

poor dieatary intake

intestinal parasites (compete for iron)

malabsorptive disease (Celiacs)

Term
Iron deficiency develops into anemia in 3 steps:
Definition

Iron depletion - serum ferritin falls

deficient erythropoiesis - Hb still normal but protoporphyrin levels up, transferrin saturation falls

iron deficiency anemia - hypochromic (low Hb), microcytosis

Term
Causes of iron overload
Definition

Blood transfussions for treatment of hemolytic disease (iron accumulates in macrophages)

Slow erythropoiesis (renal failure)

Hereditary hemochromatosis type 1 (HFE mutations)

Look for: high transferrin saturation and hemosiderin deposits (show up first in WBCs)

Term
Hemochromatosis
Definition

Common hereditary iron uptake disorder

caused by a mutation in the HFE gene leading to a repression of hepcidin expression

causes an increase of iron release from enterocytes

Term
Hb A (alpha2beta2)
Definition
Most abundant form of Hb in adults
Term
Oxygen binding properties of Hb
Definition

Hb has 4 subunits, each with a heme prosthetic group

These heme groups do not bind O2 with equal affinity

Hb does not bind O2 effectively at low O2 concentrations

As O2 levels increase, Hb becomes more efficient at binding O2 - Sigmoid shape of the Hb binding curve

Term
Myoglobin
Definition

Binds O2 with high affinity at low O2 concentrations

exibits a hyperbolic O2 binding curve

Term
Forms of Hb expressed during embryonic development
Definition

Hb Gower 1, Hb Gower 2, HB Portland

Replaced by Hb F (major form of fetal Hb)

Term
Hb F (alpha2gamme2)
Definition

Major form of fetal Hb

as development progresses, switch from gamma chain synthesis to beta chain synthesis occurs

Very high O2 affinity

Histidine residue in the beta chain required for 2-3 BPG bidning is replaced with a serine in the gamma chain

Term
alpha-like globin genes
Definition
clustered on chromosome 16
Term
beta-like globin genes
Definition
clustered on chromosome 11
Term
HS-40
Definition
chromosomal regions upstream of the alpha-like globin genes that confer high level tissue specific expression on attached genes
Term
LCR
Definition
chromosomal regions upstream of the beta-like globin genes that confer high level tissue specific expression on attached genes
Term
Structural hemoglobin variants
Definition

mutations that produce unstable Hb that have a tendency to form insoluble complexes

often form hemichrome and precipitate as Heinz bodies

form methemoglobin (Fe3+) more easily

Term
Thalassemias
Definition
Imbalanced globin chain synthesis
Term
Hb Helsinki
Definition

Beta-subunit mutation (Lys to Met) at 2,3 BPG bidning site

increased O2 affinity

Term
Hb Kansas
Definition

Beta-subunit mutation (Asn to Thr) at alpha1beta2 contact site

decreased O2 affinity

Term
Hb M Boston
Definition

alpha-subunit mutation

readily forms methemoglobin

Term
Hb M Hyde Park
Definition

Beta-subunit mutation

Readily forms methemoglobin

Term
Hb S
Definition

Found in sickle cell disease

glutamate replaced with a valine at position 6 of the beta-globin chain

Polymers distort shape of red cell - misshapen cells block microcirculation

chronic hemolytic anemia

Term
Hydroxyurea (HU)
Definition

treatment of choice for sick cell disease in adults

increases expression of Hb F

promotes Hb solubility

Reduces sickling, painful crisis, hospitalizations

Term
Hb C disease
Definition

Glutamate relplaced with a lysine at position 6 of the beta-globin chain

less soluble than Hb A so it precipitates - does not sickle

hemolytic anemia

Term
Hb SC disease
Definition
milder form of Hb S disease (sickle cell anemia)
Term
Hb E
Definition

Glutamate at position 26 of the beta-globin chain is replaced by a lysine

mutant beta-globin chain is not synthesized effictively

imbalanced globin chain synthesis leads to symptoms of a mild thalassemia

Heterozygotes are asymptomatic

homozygotes experience microcytosis, hypochromia

Term
Alpha-thalassemias
Definition

Two genes for alpha-globin on chromosome 16

manifest during development and adult life

Most often arise by deletion

Term
Bart's hemoglobin
Definition

gamma4 Hb tetramer

1 functional alpha-globin gene and 3 defective

poor oxygen carrier

Term
Hb H
Definition

beta4 Hb tetramer

1 functional alpha-globin gene and 3 defective

poor oxygen carrier

precipitates, shortening RBC lifespan

Term
Hydrops fetalis
Definition

4 defective alpha-globin genes

only embryonic Hb's can be produced (Hb Gower 1 and Hb Portland)

Incompatible with life

Term
Definition
Term
Hb Constant Spring
Definition

T is replaced by C - stop codon converted to codon for glu

alpha-globin chain length increased from 141 to 172 aa

mRNA is unstable

behaves like a alpha-thalassemia

Term
Definition
Term
Beta-thalassemias
Definition

Only one gene for beta-globin on chromosome 11

can lead to hereditary persistence of fetal Hb

Term
Lepore Hb
Definition

recombination events delete part of both beta and delta-globin genes

generates a poorly functioning globin chain

Term
Electrophoretic screening technique for Hb
Definition

Typically used in neonatal sceening for hemoglobinopathies

Insensitve and cannot resolve all abberant Hb

Term
Polymerase chain reaction-restriction fragment length plymorphism (PCR-RFLP)
Definition
Used to screen for common hemoglobinopathies with know mutations
Term
ALA synthase
Definition

control point of heme synthesis

amount of enzyme can be controlled by presence of iron

Term
Heme synthesis
Definition

ALA synthase synthesizes ALA from succinyl-CoA and glycine

2 molecules of ALA are joined to form PBG

4 molecules of PBG are joined to form uroporphyriogen

modifications of the side-chains generates coporphyrinogen and protoporphyrinogen

Ferrochelatase inserts an Fe2+ into the molecule to yield heme

Term
Regulation of heme synthesis
Definition

low heme concentraions activate ALA synthase

Liver - excess heme converted to hemin causing a downregulation of ALA synthase transcription

Bone marrow - ALA synthase transcription is controlled by EPO and availability of intracellular iron

Term
Lead posioning
Definition

inhibits the formation of PBG and ferrochelatase

leads to the accumulation of ALA and other heme precursors in heme producing tissues

causes production of zinc-protoporphyrin

causes symptoms similar to porphyrias

degree based on amount of ALA in urine

 

Term
Acute Intermittent Porphyria (AIP)
Definition

deficiency is HMBS (aka PBG deaminase)

Autosomal dominant

ALA and PBG accumulate in the urine (dark red color)

can be life threatening - causes periods of confusion and sharp abdominal pain

Term

Porphyria Cutanea Tarda (PCT)

 

Definition

Most common of the porphyrias

Deficiency of UROD

Buildup of porphyrins which can be detected in the urine - (fluorescent urine)

photosensitivity of the skin laeding to blistering of exposed areas

Late age of onset (40s or 50s)

Autosomal dominant

Term
Congenital Erythropietic Porphyra
Definition

Defect in UROS

Red, fluorescent teeth

Hairy skin

extremely photosensitive

Symptoms may be relieved by drinking blood

Autosomal recessive

Term
Pre-hepatic (hemolytic) jaundice
Definition

Elevated destruction of RBCs can lead to serum bilirubin levels that exceed the liver's capacity for glucuronation and excretion

unconjugated bilirubin in blood

no bilirubin in urine

Blood analysis shows hemolysis (reticulocyte count is up)

Hb is low

Term
Hepatic jaundice
Definition

Liver disease impairs the liver's function to glucuronate bilirubin leading to a rise in indirect bilirubin in the plasma and tissues

bilirubin in urine

Pale feces and urine

markers for liver disease may be present (ALT and AST)

Term
Cholestatic (post-hepatic) jaundice
Definition

Gallstones or neoplasias can obstruct the biliary duct, impairing the liver's ability to excrete unconjugated bilirubin into the feces

pale feces but intense urine

conjugated bilirubin in blood and urine

markers of cholestasis (alkaline phosphatase)

Term
Crigler-Najjar syndrome
Definition

deficiency in bilirubin glucuronyl transferase

genetic prehapatic jaundice

Term
Vascular injury
Definition

Damage to vessel wall exposes collagen and tissue factor to flowing blood

causes downregulation of anti-coagulationg substances

collagen - activates intrinsic pathway and activates platelets

tissue factor - activates extrinsic pathway

coagulation pathways result int he activation of thrombin

Term
Platelets
Definition

anucleated cells produced from megakaryotes in response to the hormone thromboprotein

life span of 9-10 days

normal levels are 200,00-400,000 per microliter of blood

have surface receptors that bind to collagen

Term
Thrombin
Definition
a strong platelet activator
Term
Dense granules
Definition
upon activation of platelets release TXA2, ADP, ATP, calcium, serotonin and epinephrine (vasoconstriction)
Term
Alpha granules
Definition
Upon activation of platelets release platelet factor 4, fibrinogen, von Willebrand factor, factor V and platelet derived growth factor
Term
GPIa and GPVI
Definition
Collagen binding glycoproteins on platelets
Term
GPIIb-IIIa
Definition
Fibrinogen binding glycoprotein complex on platelets
Term
Von Willebrand's factor
Definition

Required for adhesion of the platelet to the matrix (plug)

Binds to factor VIII

Term
von Willebrand's disease type 1
Definition

mild/moderate quantitative deficiency of vWF and factor VIII

Autosomal Dominant

Term
von Willebrand's disease type 2
Definition

qualitative abnormalities of vWF

Autosomal Dominant

Term
von Willebrand's disease type 3
Definition

Very low or undetectable levels of vWF (very rare)

Autosomal recessive

Term
Bernard-Soulier Syndrome
Definition

Bleeding time is prolonged (in some cases longer than 20 minutes)

Platelets are large

No platelet aggregation in response to vWF

Caused by a defect in the GPIb complex

 

Term
Intrinsic pathway
Definition

initiated by the partial activation of XII by interaction with collagen or other negatively charged surface

Leads to activation of factor X

Term
Extrinsic pathway
Definition

activated by tissue factor

Tissue factor binding to factor VII brings about activation

VIIa/TF/Ca2+ complex activates factor X

Term
Hemophilia type A
Definition
factor VIII deficiency
Term
Hemophilia type B
Definition
factor IX deficiency
Term
Hemophilia type C
Definition
factor XI deficiency
Term
Common pathway
Definition

Xa complexed with its cofactor Va and calcium ion activates prothrombin to thrombin

Thrombin cleaves fibrinogen to form a soft fibrin clot

Fibrin cross-linking forms a hard clot

Term
Thrombin
Definition

Factor IIa

Coagulation inhibitor - binds to thrombomodulin

Activates protein C, which together with its cofactor Protein S inactivates factors VIIIa and Va

Also can activate factors XI, V and VIII, convert fibrinogen to fibrin and activate platelets to promote coagulation

Term
Vitamin K
Definition

necessary for the formation of II, VII, IX, X, protein S and protein C

deficiency can result in acquired bleeding disorders

Term
Dicoumarol and warfarin (Coumadin)
Definition
inhibit the formation GIa residues by inhibiting the regeneration of vitamin K
Term
Ways the vascular endothelium inhibits coagulation
Definition

Archidonic acid - PGI2

Nitric oxide - L-arginine

Endothelial ectoadenosine disphosphate

Term
Arachidonic acid - PGI2
Definition

inhibits platelet function by elevating cAMP level in cells

also acts as a vasodilator

anticoagulation

Term
NO (nitric oxide)
Definition

diffuses into platelets and stimulates production of cGMP

cGMP supresses conformational change in glycoprotein IIb/IIIa - which is required to bind fibrinogen

anticoagulation

Term
Tissue Plasminogen activator (tPA)
Definition

rapid lysis of fibrin clots

cleaves plasminogen into plasmin

Term
Tissue Factor Pathway Inhibitor (TFPI)
Definition
inhibits TF/VIIa complex
Term
Factor V Leiden
Definition

caused by a R506Q mutation in the factor V gene

prevents cleavage by protein C and leads to prolonged activity causing hypercoagulability and increases risk of venous thrombosis

Term
Pallor
Definition
Sign of anemia
Term
Angular stomatitis
Definition
sign of iron deficiency
Term
Glossitis
Definition
sign of megaloblastic anemia or iron deficiency
Term
Virchow's node
Definition

Left supraclavicular node

common site of lymphatic metastasis for many malignancies

Term
Posterior superior iliac crest
Definition
preferred site for bone marrow biopsy in an adult
Term
Myeloid to erythroid ratio (M:E ratio)
Definition
3:1
Term
Most common acute cause of neutrophilia
Definition
infection
Term
Neutropenia may be caused by:
Definition

Hypersplenism

Chemotherapy

Post infection

Immune mediated disorders

Term
Serum eosinophils are elevated when:
Definition

Allergic rxn to drugs

Allergies

Helminthic infections

Maligninacies

Collagen vascular disease

Term

subtle physical sign in a neutropenic patient

 

Definition
unable to generate a significant inflammatory response
Term
When is a rectal exam contraindicated
Definition
Febrile neutropenia
Term
Definition of neutropenia
Definition
ANC = Polys + bands > 500