Exam 1 Flashcards
Positive cooperativity
oxgen binding to hb alters confirmation to increase affinity for other oxygen molecules
Acute chest syndrome associated complications
kidney and liver failure
How does temp influence saturation curve?
shifts to the right
Vitamin B12 absorption
in stomach with Intrinsic Factors, gets absorbed in ileum and is released from IF
Thrombopoetin
differentiates and matures patelets into periphery, originates from other cells and small component of kidney
Treatment of Chronic infection/inflammation/malignancy
treatment of underlying disease to decrease cytokines and interluekins
Redicualte in circulation
1-2 days
Idiotype
difference in CDR due to specificity.
Pro-Bcell
just heavy chain with VDJu
Calculated Hematocrt
RBC * MCV
Alpha globin in DNA
on CH16, 2 paternal and 2 maternal; Zeta during development
post-capillary venules in lymph node
high-culoidal to react to lymphocytes
too few monocytes
monocytopenia
path of lymphocyte
bind to high cuboidal cell, pass between into the node to lymph, to lymph channels, to thoracic duct to venou blood and back
IgD
long hinge region, 5 mg/dl; 180,000 D
Hb Portald 1
Z2Y2
RDW calculation
standard deviaiton of values of MCV
TLR
bind to initiate inflammatioon cascade and ultimately activate NFkB
Allotypic exclusion
like X inactivation of antibodies, recombination can be done if initial antibody is unsuccessful
Hemolytic anemais
Hereditary spherocytosis, enzyme disorders, autoimmune hemolytic anemia
Fe Deficient - Concentrations
99% a1; 2% A2;
MCV
Mean Corpsular Volume, average volume of RBC
Spectrin, ankryn, band 3 alll..
lead to destabalization of lipid bilayer and microspherocytes –> deformability
How does temperature affect oxygen affinity
Higher temperature unloads oxygen easier
Retic count in hemolysis
increases
Immunogen
antigen that generates immune response
symptoms of G6PD deficiency
acute anemia, hyperbilirubinemia, hemolysis, reticulocytosis, blister cells, bite cells, heinz bodies
Direct Antiglobin testing
IgG, C3d, C4dl tests directly in patient blood
How does dropping the pH shift the Saturation curve
to the right, -lower the affinity of oxygen
monocytes
immature macorphages or dendritic cells comprise 2-8% of WBC
Hb Poole
mutation in gamma chain, phycial unstable variant; infants have hemolytic anema, but it resolves with time.
Characteristics of monopoesis
delicate chormatin pattern, gains vaculoles during maturation, abundance of cyto
Maturation of B lymphoblast
to B lymphocyte to Plasma cell with lots of golig and ER
what factors influence oxgygen dissocation?
pH, temperature, 2,3-BPG
Papin
reduces disulfide bonds to create 2 Fab and 1 Fc
Gestational Hemoglobins
Gower ! And II, and Portland I and II
IgE
extra long C4, 0.2 mg/dl; 190,000 D
HbE
Beta 26 Glu –> Lys; SE asia
Direct Current Technology
blood passes through electrodes and creates resistance in proprotional to cell size. RBC and platlets could be measured simultaneously.
Hypocellular marrow is called_
autoimmmune attack, viral attack
What causes hypercellular marrow?
hypoxia, increase in HGFs
Taut
T hb in low oxygen situations. Four unoccupied sites, binding affinity is low.
Where does megakaryopoiesis take place?
in bone marrow along vascular sinuses and integrates into lumen of vessels and release plasma into bloodstream
post-capillary venules in lymph node
high-culoidal to react to lymphocytes
Germinal center
sites of intense lymphocyte division (b cell). Increase cytoplasm compared to nucleus
Fc
botton region of heavy chains with carbohydrate to prevent collapse
VCAM1
increased in SCD, increased cell adhesion to endoethelium
Maturation of B lymphocyte
to B lymphoblast to Plasma cell with lots of golig and ER
Where does Hb F remain high?
Infants with mothers who have diabetes, hemolytic anemia, bone marrow diseases
Alpha Thal concentations
97 A1; 3% Ab2;
mature B cell
sIgM and sIgG with same specificity
Too many eosinophils
eosinophilia
Monopoesis
Requires M-CSF; monoblast –> promonocyte –> monocyte
Trends in Eosinophils
always 0-6%
lifespan of sickled cell
SC - NBS
FSC
Cholelithiasis
gallstones due to increased bilirubin, –> obstruction
Retic count - SCD with B+ Thal
3-5%
Low Affinity Hb variants Symptoms
mild anemia, cyanosis
What prevents infection in SCD?
penicillin porphylaxis
alpha -thal NBS
Fbarts
primary RNA transcript in antibody genes
made through Cu and Cdelta
Decreased RBC survival in thalassemia
increased retic count, intreacsed intracellular RBC contnets, splenomegaly, bilirubin gallstones, anemia
MCHC calculation
hb/hct
How does mRNA for antibody form?
splicesome splices out primary RNA to make VDJ u or VDJdelta
monocytes
immature macorphages or dendritic cells comprise 2-8% of WBC
NK cells
differentiated B cell, with immunity and survelliance
TNF
stimulated by malignancies and sepsis, to decrease iron and therefore erythropoeitin and inhibit RBC production
what converst bilirubin to glucuronic acid
CYP450 in liver
Splenic Function
clearance of intravascualr particles; adaptive immune resonse: origin of igM
what joins first in VDJ sequence
DJ
Beta Globin in DNA
CH11, Epsilon during development, one copy from each parent
Too many neutrophils
neutrophilia
paracortex in lyph node
not as dense as cortex, houses the T cells
C5A
chemotactic agent to attract bacteria in complement pathway
reticulcoytes time in marrow
3-4 days
MCH
mean corpsular hemoglobin; weight of Hb of the average red cell
what joins first in VDJ sequence
DJ
clinical features of renal insufficiency
fatigue, pallor decreased exercise tolerance, dyspena, tachypena, anemia - unrepalted to kidney dysfunction
Opsonizing
opsonizationÿis a means of identifying the invading particle to the phagocyte; labled with igG and C3B to act as handles for phagocytosis
Infections with SCD is due to
due to spenid dysfunction and aplastic crisis
IgD
long hinge region, 5 mg/dl; 180,000 D
order these in order of sicking potenial - SS, SF, SC, SF
SF
Splenic Sequestration
blood flow into sinusoids is occluded and unable to flow out. Splenomegaly
Complications with hereditary spherocytosis
aplastic crisis and cholelithiasis
IgA
dimer with J chain and secretory component, 400,000D
200 mg/dl
IgG Serum
1000 mg/dl; lightest at 150,000 D
Granulopoiesis
creation of eosinophil, basophils, and neutrophils
calculated components of a CBC
Hct, MCV, mean capsular hb, mean capsular hb conc, RDW, absolute leukocytes
Mononulcear cells make
monocytes and lymphocytes
2,3 - BPG
byrpoduct of anaerobic glycolysys. During increased O2 use, hypoxia, chronic anemia, more is produced because glycolysis increases
what factors increase sickling?
deoxygenation, potassium, dehydration, Hb concentration
DAMPS
damage associated molecular patterns - sense internal damage of our own cells with TLR and attarct phagocytic cells
Complement pathway
completes antibody process by activating C3 to activates membrane attach complex
Immune complex
froms when antibodies bond to antigens and cross link due to divalnce at equal concetnraiton of antibody to antigen.
T Cell and B cell distribution in spleen
T cell surround arterioles and B cells surround them
Endothelial-1
vasoconstrictor, increases in SCD
Microcytic anemia types
Fe deficiency, thalassemia, lead poisoning
when does fetus make igG?
3 months old
Direct Antiglobin testing
IgG, C3d, C4dl tests directly in patient blood
how is a differential performed?
blod film (wdge, cover glass, spinner), air dry and fix with MeOH, wright-giemsa stain
Lab finding of AIHA
Increased Retic, increased bilirubin, hemoglobinuria, warm + Dat for igG or Cold + Dat for complement
paracortex in lyph node
not as dense as cortex, houses the T cells
Hb Chesapeak symptoms
hypoxia, generally well affected and don’t need treatment
Hb Zurich
point muations to increase binding to CO
Eosinophils in Differential
Bi-lobed nucleus, large red granuals
igM
pentamer, extra long C4, S-S bonds and One J chain, 900,000D; 100 mgdl
seg
muliple lobes with chormatin band, small size, pink cyto
Too many basophils
basophilia
Absorption of Folate
in jejunum where it is hydrolyzed, reduced, methylated into methyltetrahydrofolate.
what is practicla reference interval in CBC?
mean +- 2 SD
IgM (classes)
immunization to activatio of complement, V=10, but binds to 2. vicsous, only ab made in fetus
Immunological Aging
as we age, our memory cells outnumber our na‹ve cells and cant respond to new antigens.
T Cell and B cell distribution in spleen
T cell surround arterioles and B cells surround them
Opsonizing
opsonizationÿis a means of identifying the invading particle to the phagocyte; labled with igG and C3B to act as handles for phagocytosis
Clonal Selection theory
cells make one antibody, choice is randome dependent on outside signals.
HBO
Arab; Beta 121 Glu –> lys (basic); Africa, Middle east
Domains in antibodys
made of 7 Beta sheets for rigidity. The region sin between the sheets form the variable regions. Held together by disulfide bonds
Lymphocytes in differential
scant cyto with dense, round nuclus
Cyanosis
blue/grey color skin and mucus membrane; Too must deoxyhemoglobin 1.5 g/dl methemoglobin (8-12%); sulhemoglobin >0.5 g/dl
Hb at birth
65-95% Hb F and 20% HbA
Warm
IgG, poor complement activity activates spenic macrophages and extravacualr hemolysis
when does fetus make igM?
3 months gestation
Basophils - immuno
acidic cells, release histamine, Mast cells in tissue; 0.5-1%
Fetal Hemoglobin
alpha2gamma2
How is bone marrow biopsy performed?
through ilica crest, suction to pull out reiculyn fibers; use a core to pull out a piece of marrow that contains bone and cells.
Leukocyte absolute count
Diff% * WBC / 100
HbS
Beta 6 Glu –> Val (acid to hydrophobic); africa, india, med
Endocrine disorders lab findings
mormochronic and cytic, decreased retic count
AS - NBS
FAS
MCV calculation
Hct/RBC count
Humoral
antibody mediated immunity
What contributes to antibody diversity
recombination, exonucleases, terminal deoxynucleotidyl transferase added random NT to N region
Protein Calorie Malnutrition
anemia due to lack of protein and calories
what is %sat at 60 mmHg
90%
Normocytic anemia types
anemia of chronic disease, sickle cell
Symptoms of AIHA
acute or chronic anemia, pallor, jaundice, dark urine, splenomegaly
Splenic InfarctioN
insufficient bloodflow to spleen (usually by age 4 in SCD)
Iron Deficienty lab finidngs
decreased MCV, RBC, MCV/RBC >13, incrase RDW, Decreased ferritin, normal electrophorysis, response to Fe
Immune complex
froms when antibodies bond to antigens and cross link due to divalnce at equal concetnraiton of antibody to antigen.
EB+
FEA
G-CSF
helps early blast stage differenitiating into myeloid lineage as opposed to lmphoid.
C5A
chemotactic agent to attract bacteria in complement pathway
Hematocrit
erythrocote volume/whole blood volume - centrifugation
pathway for malignancis/sepsis in anemia
production of TNF and Interfereon Beta
what does manual differential add?
morphology of RBC, WBC, platelets, abnormalities in peripheral blood, relative or absolute quantification of WBC populations
Hemopexin
binds to free heme from methemogobin to be processed in liver to make bilirubin
Fab
top part of one heavy and one light chain
Methemoglobin - how do you get it?
acquired or genetic
what kind of infection is caused by SCD
encapsulated bacteremia - strep, hemophilus influenza, meningococcus
Affinity Maturation
with each replication CDR varies, if antibody encounters antigen it stays in the game.
igM
pentamer, extra long C4, S-S bonds and One J chain, 900,000D; 100 mgdl
Hemoglobin amount - SCD trait
14-16 mg/dl
Maturation of T lymphocyte
T lymphoblast
How long does MVC take to get back to normal in B12/Folate defidiency
months
How long does Hb take to get back to normal in B12/Folate defidiency
1-2 weeks
when does fetus make igM?
3 months gestation
Sickel Mephropathy
10-15%; hyperfiltration and enlarged glomeruli, porteinuria
what can you measure with flow cytometry?
Reticulocyte count, nucleated RBC types, platelet count
Treatment of hereditary spherocytosis
supportive care, folate, splenectomy
Epitope
region of antigen that interacts with CDR, discontinous or continous, falt, also called antigenic determinants. Interacts with CDR non-covalenly.
what globin chain makes antibodies
gamma (called immunoglobulin
Rag recombinase
enzyme responsible for looping out random parts of DNA to greate VDJ recombination
Symptoms of AIHA
acute or chronic anemia, pallor, jaundice, dark urine, splenomegaly
medulla role lymph node
filter
measuring MCV
mean height of the voltage pulse during RBC count
hemoglobincyanide method
combine bood with potassium cyanide and potassium ferricyanide, product absorbs light at 540 nm. Can detect how much Hb based on absorbance.
macrocytic anemia types
vit B12 and volate deficience
HbH
B4
Retic count - HbSC
3-5%
HbEE
FE
Tolerogen
antigen that does not ellicent and immune response
Less severe sickle cell types
SB+, SC, trait (no anemia)
how to limit iron loading
erythroectapheresis and phlebotomy prior to transfusion
Mitotic pool of granulopoiesis
4-5 cell divisions, where they enter the storage pool with no more cell division
what globin chain makes antibodies
gamma (called immunoglobulin
Retic count - SC Trait
1-2%
Pulmonary hypertension
increased pressure on pulmonary arteries, most often due to sickle lung disease
What type of bilirubin is expelled in feces?
fecal urobilinogen
Lab findings of lead intox
mild/mod anemia, microcytosis, mild hypochormia, basophilic stippling, increase zinc protoporphyrin.
Sickle lung disease
25-40% of SCD; preogressive obliteration of pulmonary vasculature; leading cuase of death in adults with SCD
Immunological Aging
as we age, our memory cells outnumber our na‹ve cells and cant respond to new antigens.
Alternative complement pathway
cell wall structures in microbes activate C3 directly in absense of antibody (innate)
HbC
Beta 6 Glu –> Lys (acid to base); west africa
RDW
Red blood cell distribution width
order of antibody sequence for DNA
VDJ
Hb A2
alpha 2 delta 2
iron in RBC transfusion
1ml has 1 mg Fe; 3-4 g Fe/yr
Idiotype
difference in CDR due to specificity.
Bilirubin in extravascualr hemolysis
porphyrin ring forms bilirubin, which is conjugated to glucoronic acid in liver and then in bowel is converted to urobilinogen
Complement pathway
completes antibody process by activating C3 to activates membrane attach complex
Pathophysiology of thalassemia
Imbalance alpha and beta, excess globin participate, ineffecient erythropoesis
Monocytes in differential
largets, irregulat nulcues, fine granuals, vacuolated cytoplasm
Complications with hereditary spherocytosis
aplastic crisis and cholelithiasis
Eosinophils - immuno
basic cells, bind to major basic proein, kill parasites. 1-4%
Sickle Dex
hemolyze blood with reducing agent, and release Hb. Sickle is less soluble. Can detect SBD, but not type of disease
Hb Portland 2
Z2 B2
half life of igG?
3 weeks
What is P50 or hb 50% saturated?
27 mmHg
Hydroxyurea and bytyrate
fetal Hb induction; reduces sickle hb polymerization, decreases WBC count
Granulopoiesis starts with_
myloblast to promeylocytes that splits into the three idfferent lineages as bands and then seg.
Cathelicidin
bind to negative charged pathogens and bore holes - located on skin/mucosa
Allotype
differences in antibody due to mom or dad, in non-CDR region
Beta thal trait concentrations
94 A1; 4% A2; 2% HbF
EB0
FE
Anemia Concentration - normal
97% A1 and 3$% A2;
SB+ = NBS
FSA
Microcytic anemia types
Fe deficiency, thalassemia, lead poisoning
Heptoglobin
plasma proin that binds to HB dimer that is created in intravascular hemolysis; removed from circulation in liver
order of antibody sequence for DNA
VDJ
erythroceytapheresis
erytrocytes separate from whole blood
Neutrphils in Differential
Acidic cytoplasm, 2-5 distinct lobular nuclues
Lymphocytes - immuno
T and b cells; prominent WBC in children; 20-40%
Vaso-occlusive Pain
acute complication of SCD; pain in muslces and back and require opiates and antiinflammatory.
when are transfusions used?
only when severity has potential for cardiovascualr decompensation
half life of igG?
3 weeks
50-60% methemoglobin
stupor, bradycardia, respiratory depression, convulsions, acidosis
is normal good?
in certain diseases tests are expected to be abnormal. Failure to chagne is bodys inability to respond approprioately.
Hemoglobin amount - SCD
6-9 mg/dl
Causes of V12 deficiency
pernicicious anemia - autoimmune
Biochemical test of Folate Deficiency
decreased serum folate.
RBC range for Direct Current
35-250 fl
Schlling Test
ingetion of radiolabeled Vit B12, it gets absorbed into blood stream, give flushing dose of normal V12 IM at 2 hours; Kidney normally excretes 3-35% of absorbed radioactive in 24 hours
lab finding for hereditary spherocytosis
increased retic count, decrased MCV, spherocytes
Where does curve lean towards in gel test for Ab and AgWhere does curve lean towards in gel test for Ab and Ag
Ab (they are larger)
What malignant diseases cause anemia
carcinoma, hodgkins disease
what causes increase iron absorption
ineffecte RBC production, low hepcidin, mutations in HFE
stroke in SCD
cellular adhesion, loss of vasoregulation by increased endothelial 1 release, and decreased NO.
SCD concentrations
2-30% HbF 70-98% HbS
Sickle Cell Trait Risks
kidney complications: microscopic hematuria, renal papillary necrosis, isosthenia, chronic kidney disease; blood clot risk; splenic infarction, rhadomyolysis
Cold
IgM (some IgG) bind in extremitie and return in warmth to acivate complement and intravascualr hemolysis
Polymorphonuclear cells
eosinophils, basophils, neutrophils
use of myoglobin
oxygen storage in muscle
Alpha thalassemia lab findings
decrease MCV, increased RBC, MCV/RBC
Class switching
V domain stays the same, but splicing occurs at DNA level to cut out other constant regions. Cannot go back to the ones cut out
HbH thalassmeia
3 deletions; moderate anemia, makes B4 to compensate, transfusion depent on stress
Methemoglobin symptoms
asymptomatic, but low sat; dark blood when mixed with air.
How does increasing pH shift the saturation curve?
Shift to the left - increased affinity
Hydroxyurea and bytyrate
inductio of HbF
primary RNA transcript in antibody genes
made through Cu and Cdelta
PAMPs
pathagen associated molecular patterns, recognize forein structures through interaction with PRR
IgA
dimer with J chain and secretory component, 400,000D
HB SB0 concentrations
3% A2; HbF 2-30; S 70-98
macrocytic anemia types
vit B12 and volate deficience
PRR
pathogen recognition receptors are on surface or inner membrans (TLR)
symptoms for PK deficiency
variable anemia, hemolysis, splenomegaly, gallstone, aplastic crisis
DAMPS
damage associated molecular patterns - sense internal damage of our own cells with TLR and attarct phagocytic cells
Beta thal and Fe deficient concentrations
96 A1; 3% A2; 1% HbF
gallstones due to increased bilirubin, –> obstruction
decreases pyruvate formation and decreases ATP production; loss of membrane plascticity and increased rigidity.
Humoral
antibody mediated immunity
Types of anemia in Hereditary Spherocytosis
5% sever; 60-75% moderate; 20% mild
methemalbumin in hemolytic anemia
increases
Lectin pathway
complement pathway; mannose bidning protein binds to bacterial structures to activate Complement pathway MBP- 4-2-3-5-6-7-8-9
Sideroblastic anemia clinical/lab
variable anemia, hypochromia, microcytosis, accumulation of iron in mito
G-6PD Def mechanism
deecrased production of NADH, reduction in glutathione, and protecton from hydrogen peroxide.
medulla role lymph node
filter
clinical features of Chornic infection, inflammation, malignancy
dependent on underlying disease
Current mothod of measuring Hb
lyse RBC and WBC, alter globin and oxidize heme, sodium lauryl sulphate binds to form colored complex and measure the absorbance.
how does chronic inflammation/infection cause anemia?
stimulates IL1 and interferon gamma
Neutrophil killing
1) phagocytosis or 2) degranulation (spews out granules into enironment to cause necrosis and inflammation)
Gower 2
alpha2E2
Warm
IgG, poor complement activity activates spenic macrophages and extravacualr hemolysis
Risks in transfusion
infection, allo-immunization; iron overload
Immunogen
antigen that generates immune response
Iron loss per day
1mg/day; fixed; sloughed mucosa, meses
iron overload toxicity
ears, hearing, bone, liver, kidney
Trend of neutrophils over lifetime?
45-50% at birth until 2-12 years old increase to 40-75%
Treatmetn of acute chest syndrome
transfusion to maintain 9-10 mg/dl, induction of HbF, bone marrow transplant
what happens in thalassemia
Anemai, bone marrow expansion, extramedullary hematopoesis
how does pH affect O2 dissociation?
Oxygen is held tightly in basic conditions and released in acidic
Immature B cell
cIgM and surface IgM; clonal deletion
heptoserum levels in hemolysis anemia
decrases
Hereditary Spherocytosis
most often due to spectrin deficiency, causes anemia jaundice, splenomegaly. Microspherocyte and osmotic fragility
Monopoesis circulation
marginal pool for 20 days and can go into tissue to become macrophages; circulation is short lived.
Mononulcear cells make
monocytes and lymphocytes
Retinopathy
causes neovascularization (sea fan formation) and venular occlusion (sea fan infarction); redintal detachment, hemorrahge, and blindness
Too few neutrophils
neutropenia
How long does blood count take to get back to normal in B12/Folate defidiency
8 weeks
Hemoglobin amount - Sickle B0 Thal
6-9 mg/dl
Fc
botton region of heavy chains with carbohydrate to prevent collapse
Brend of Bands over lifetime?
always 0-9%
Allotype
differences in antibody due to mom or dad, in non-CDR region
Transcoalbumin BP II
binds to Vitamin B12 after ileal abosprtion and promotes liver sotrage or transfer to tissue (bone marrow).
oxidation of Hb_ from G6PD deficience
denatures Hb so it attaches to membrane to create heinz bodies, trapping/deformability and extravascualr hemolysis
Clinical manifestations of thalassmeia
Underproduction of normal Hb and decreaesd RBC survival
Eosinophils - immuno
basic cells, bind to major basic proein, kill parasites. 1-4%
Lead intoxification and anemia
lead inhbits protoporphyrin ring syntehsis and iron from forming hemoglobin
G-6-PD deficiency
X-linked recessive; prevalent in tripical eastern hemisphere, selective resistance to malaria
Peyer Patch
lymph node I n gut that underlies mucosa of SI; located by goblet cells. Phacogytose proteins and particles for luminal transport. Determine if food or threat
IgE
extra long C4, 0.2 mg/dl; 190,000 D
IgE (class)
binds to mast cells and eosinophils, triggers histamine release for allergic reactions; parasite killer
hematologic changes in folate and B12 deficiency?
megablastic, macrocytosis, decreased Retic index, hypersegmented neutrofils, increased biliruin and LDH
Extravascualr hemolysis
done by macrophages in RE system of spleen
Dendritic cell mechanism
cytokine,chemokine, stimulate immature DC to phagocytose everything, activate DC enters lymphatic cystem to nearly lymph node, puts digested pathogen on surface as antigen presentingmolecule for T and B cell –> activates adaptive response.
Partial pressure in tusse
40 mmHg
why is aplastic crisis dangerous for hereditary spherocytosis?
severe drop in hct due to shortened RBC lifespan
lymph flow in lymph node
entry in periphery, through subscapular sinus through middle of node and out of hilum
Clonal delection
if IgM on surfae encounters self, it initiates apoptosis. If it doesn’t encounter antigen in 24 horus, unlikely to antibody towards self and can surive
Flow Cytometry
lysis regaent performates membranes but leaves cells intact, label DNA and RNA anre fluorescently labeled, scattergram according to fluroescence and internal struture. Strongest fluroescence is immagure with high NA content.
why is aplastic crisis dangerous for hereditary spherocytosis?
severe drop in hct due to shortened RBC lifespan
Hemolysis in SCD
creates more free Hb and inhibits NO release and vasodilation; also increases erythroid arginase to degrade arginine and precursor to NO.
Treatment of Beta thal
transfusion to maintain 9-10 mg/dl, induction of HbF, bone marrow transplant
HbA2
2% of normal HbA; functions like HbA1, but more heat stable and slightly higher oxygen affinity.
Lymphocytes - immuno
T and b cells; prominent WBC in children; 20-40%
C1-esterase inhibitor
regualtes the actiation of C3 so complement pathway is not always activated
Relaxed hb
loosey goosy hb, as binding to oxygen increases salt bonds are brokena and affinity increases
Band
more than 1/2 dimeter of nuclear indentation
INF gamma
inhibits erythroid proliferation and decrease RBC production due to chronic infection and inflammation
G-6PD Def mechanism
deecrased production of NADH, reduction in glutathione, and protecton from hydrogen peroxide.
Folate and Vitamin B12 do_
support proliferation and maturation of RBCs, methionine sysntehsis, purine and pyrmidine biosynthesis, production of thymodylate for DNA synthesis
oxidation of Hb_ from G6PD deficience
denatures Hb so it attaches to membrane to create heinz bodies, trapping/deformability and extravascualr hemolysis
what happens with stress to reticulocytes
early release by 5-7 days
Trends of Lymphocytes over lifetyme
1-3 days 15-30%; 4-14 days 4-18%; 15 days to 2-12 years 2-14%; 13 + 2-11%
Pro-Bcell
just heavy chain with VDJu
IgM (classes)
immunization to activatio of complement, V=10, but binds to 2. vicsous, only ab made in fetus
Gower 1
Z1 E2
Hb Koln
mutation in beta chain, physican unstable varian. Has increased oxygen affinity.
Hb SC concentrations
Fab
top part of one heavy and one light chain
Methods for SCD testing
Sickle Dex, HB separation, isoelectric focusing, HPLC
Chronic inflammatory disease cause anemia
rheumatoid arthritis, systemic lupus erythematosis, rheumatic fever
path of lymphocyte
bind to high cuboidal cell, pass between into the node to lymph, to lymph channels, to thoracic duct to venou blood and back
IgA (class)
made by plasma cell in mucus membrane; secretory component, small amoutn of monomer in IgA plasma
isosthenuria
urinary concentratin defect
Hemolytic anemais
Hereditary spherocytosis, enzyme disorders, autoimmune hemolytic anemia
adverse effects of iron overload
hepatic fibrosis and cirrhosis, endocrinopathies, cardiomyothpathy and sudden death
Treatment of folate deficiency
1mg/day orally or parenterally
How does 2,3- BPG concentration affect oxygen affinity
stabalizes T conformation and leads to decreased oxygen affinity
Trends of Monocytes overtime
1-3 days 15-30%; 4-14 days 4-18%; 15 days to 2-12 years 2-14%; 13 + 1-3 days 5-20%; 4-14 days 4-18%; 15days to 2-12 years 2-14%; 13+ 2-11%
when is EPO used?
when there is an absolute deficiency or decrease of EPO out of proportion to hct
IgA (class)
made by plasma cell in mucus membrane; secretory component, small amoutn of monomer in IgA plasma
Germinal center
sites of intense lymphocyte division (b cell). Increase cytoplasm compared to nucleus
Hydroxyurea and complications
50% reduction in acute pain events, no evidence for chronic organ injury
Tolerogen
antigen that does not ellicent and immune response
how much can bone marrow production increase
6-8 fold
Trends in basophils
always 0-2%
Mekagaryopoiesis
Thrombopoesis. Megakaryblast matures to mekakarycoyte –> platelet.
When does Fetal hemoglobin predominate
after 8 weeks gestation.
Spleen anatomy
Red contains phagocytic cells to make RBC and filter RBCs; white: lymphocytes
Risks in splenectomy
sepsis 1) vacciantion before, prophylatic antibiotidies, see doctor if fever above 38.5
Saturation of heptoglobin
due to increased hemolysis and leads to oxidation to methemglobin
Clonal delection
if IgM on surfae encounters self, it initiates apoptosis. If it doesn’t encounter antigen in 24 horus, unlikely to antibody towards self and can surive
Where in the body is it acidic?
At tissues - CO2 is produced at tissue due to metabolism, and carbonic anhydrase converts in bloodstream CO2 and water into carbonic acid to eventually convert to bicarbonate and drop the pH
Polychromasia
premature release of reticulocytes from marrow - have bluish tint
Beta0 thal NBS
F
G-6-PD deficiency
X-linked recessive; prevalent in tripical eastern hemisphere, selective resistance to malaria
NK cells
recognize basence of normal surface molecules
Barts Hb
Y4
cortex in llymph node
tightly but motile lymphocytes in follicles
Sideroblastic Anemia
imparied production or protoporpyrin or incorporation of iron
Platelet Counting range
6-36 fl
when does fetus make igG?
3 months old
Basophils - immuno
acidic cells, release histamine, Mast cells in tissue; 0.5-1%
Acute complications of SCD
Vaso-occlusive pain, acute chest syndrome, infection, spelnic infarction and sequestration, stroke
Lab/clinical findings of folate and B12 deficiency
megaloblastic anemia
Fecal urobilinogen can go through three pathways
1) fecal mater, 2) kidney for excretion 3) EHC recycling
measureable components of CBC?
Hb, Hct, RBC count, MCV, WBC count, Platelet count, mean platelet volume
Protein calorie malnutrition laboratory/clinical
variable anemai, normochromic and normocytic
Cooperative binding
creates a sigmoidal curve and allows for binding in lungs and release at tissue.
Beta Thalassemia lab findings
decrease MCV, increased RBC, MCV/RBC
Cathelicidin
bind to negative charged pathogens and bore holes - located on skin/mucosa
Bohr effect in Fetal hemoglobin
As blood flows through placenta, H+ is transferred from maternal to fetus circulation to increase pH and and oxygen follows from mother to fetus
Cellular response with folate and Vit b12 def
increase cell size, arrest in S phase of mitosis. Cells are degraded and have ineffecitve erythropoiesis.
Aplastic crisis
associated with parvovirus B19; causes low retic, severe anemia, pallor; rahs on arms and face
Hemoglobin Chesapeak
High affinity Oxygen Hb due to a single point mutation; cauese reduced delivery to tissues and increase EPO release and increased RBC production
what amino acids are on outer surface of hb
lysine, arginine, glutamic acid to keep hyrophilic
where does heme bind to alpha globin
87th amino acid
Rag recombinase
enzyme responsible for looping out random parts of DNA to greate VDJ recombination
symptoms for PK deficiency
variable anemia, hemolysis, splenomegaly, gallstone, aplastic crisis
Transfusion above 10 g/dl
dangerous cause hyperviscosity
Hydrops fetalis
4 deletions, heart dtrain due to decreased blood volumne; subcutaenous edema
Treatment of Renal insufficiency
EPO and treatment of co-morbid conditions
Beta+ thal NBS
FA
Metamyelocyte
must be half diameter, nuclear indentation
what causes RBC death?
decreased enzymatic activity, oxidative injury, change in Ca balance, chagnes in membrane carb, antibodies, surface constituents
PAMPs
pathagen associated molecular patterns, recognize forein structures through interaction with PRR
Too many lymphocytes
lymphocytosis
symptoms of G6PD deficiency
acute anemia, hyperbilirubinemia, hemolysis, reticulocytosis, blister cells, bite cells, heinz bodies
Chronic Complications of SCD
Sickle lung disease, pulmonary hypertension, sickle nephropathy; retinopathy, leg ulcers; avascular necrosis
lab finding for hereditary spherocytosis
increased retic count, decrased MCV, spherocytes
Negative aspects of direct current technology
counts all cells, so includes white cells. Can not discriminate aggregated plateltes, so platelets could be artificially low
Where does curve lean towards in gel test for Ab and AgWhere does curve lean towards in gel test for Ab and Ag
Ab (they are larger)
lab tests for PK def
mild to severe anemia, increase retic, no specific morphology
Hb SB+ Concentrations
25-45 A1; 3% A2; 2-30 HbF; 55-75 HbS
What is in urine during increased intravascualr hemolysis
hemosiderin, hemoglobin, methemglobin
how to do reticulocyte count?
Flow cytometry
Affinity Maturation
with each replication CDR varies, if antibody encounters antigen it stays in the game.
lab tests for PK def
mild to severe anemia, increase retic, no specific morphology
Epitope
region of antigen that interacts with CDR, discontinous or continous, falt, also called antigenic determinants. Interacts with CDR non-covalenly.
C1-esterase inhibitor
regualtes the actiation of C3 so complement pathway is not always activated
Cellularity
White spaces - hematopoeitic spaces (100-age). Celularily decreases with age
Most severe sickle cell disease
SCD and SB0
Hemoglobin amount - SCD with C
10-12 mg/dl
Treatmetn of Lead intoxication
chelation of lead
Biochemical test for B12 deficiency
Increases erum folate, increasd serum methylmalonic acid, increas serum-2-methyl ctiric acid
inheritance of hereditary spherocytosis
75% AD, 25% AR
Mast cell fromation
requires SCF or come from the basihilic lineage with IL3
PRR
pathogen recognition receptors are on surface or inner membrans (TLR)
Classical pathway of complement
antigen binds to igG (2) or IgM (1) to activate allosteric change to FC to allow C1q to bind to activate cascate of 1-4-2-3-5-6-7-8-9
Clonal Selection theory
cells make one antibody, choice is randome dependent on outside signals.
Immature B cell
cIgM and surface IgM; clonal deletion
NK cells
recognize basence of normal surface molecules
Dendritic cell mechanism
cytokine,chemokine, stimulate immature DC to phagocytose everything, activate DC enters lymphatic cystem to nearly lymph node, puts digested pathogen on surface as antigen presentingmolecule for T and B cell –> activates adaptive response.
Treatment of Endocrine Disorders
Hormone replacement
What contributes to antibody diversity
recombination, exonucleases, terminal deoxynucleotidyl transferase added random NT to N region
Isoeletric Focusing
like electrophoryesis; pH gradient imbedded in gel and migrates to isoelectric point
blood in lymph node
entry and exit through hilum
Splenic Function
clearance of intravascualr particles; adaptive immune resonse: origin of igM
IgD (class)
B cell recptor antibody (antibody forming cells)
What is % sat at 30 mmHg
60%
Renal insufficiency in Anemia
no kidney function means no EPO, so no erythroid proliferation and decrease RBC production
lab finding for hereditary spherocytosis
increased retic count, decrased MCV, spherocytes
SB0 - NBS
FS
Intravascular Hemolysis
breakage of RBC in vascualr system
why is myoglobin not a good oxygen carrier
high affinity for oxygen at low oxygen concetnraitons - can’t release at tissues.
Cold
IgM (some IgG) bind in extremitie and return in warmth to acivate complement and intravascualr hemolysis
Maturation of T lymphocyte
T lymphoblast
IgD (class)
B cell recptor antibody (antibody forming cells)
>30% methemoglobin
fatigue, lightheaded, headache
Partial pressure in lungs
100 mmHg
which has neurological features B12 or folate?
B12 - sensory loss, proprioception loss, ataxia, gait distrubances, Babinski reflex, cognitive and emotional changes.
Lab finding of AIHA
Increased Retic, increased bilirubin, hemoglobinuria, warm + Dat for igG or Cold + Dat for complement
INFbeta
Triggerd by Malignancies and sepsis, to inhibit erythroid proliferation and decrease RBC production
Why does transfusion help with beta thalassemia
supresses inate RBC production and marrow expansion
igG (classes)
most abundant, passes placent to fetus, longer effect after immunization, half life of three weeks, opsonizing, 2 igG to activate complement
Lectin pathway
complement pathway; mannose bidning protein binds to bacterial structures to activate Complement pathway MBP- 4-2-3-5-6-7-8-9
Howell-jolly bodies
basophilic nuclear remnants in erthyrocytes - due to damaged or absent spleen
what is %sat at 40 mmHg
75%
chronic infections that cuase anemia
pulmonary abscesses, meningitis, chronic GU infection
how long in storage pool for granulopoiesis
5-7 days beore going into vessles walls in marginated pool or circulation in peripheral blood.
Hemoglobin amount - B+ Thal
11-13 mg/dl
How does mRNA for antibody form?
splicesome splices out primary RNA to make VDJ u or VDJdelta
Too many monocytes
monocytosis
Cholelithiasis
gallstones due to increased bilirubin, –> obstruction
lymph flow in lymph node
entry in periphery, through subscapular sinus through middle of node and out of hilum
which deficiency is faster, folate or B12?
Weeks to months for folate, very slowly for B12 (years)
Acute Chest Syndrome
Rib/vertebral infarction, infection, bone marrow embolysn lead to decreased blood O2, chest pain, fever, decreased hemoglobin
IgG Serum
1000 mg/dl; lightest at 150,000 D
is serum creatinine a good indiciator of kidney function?
no - can have widely different GFR
mature B cell
sIgM and sIgG with same specificity
Treatment of Structural Hb Variants
folic acid, splenectomy not curative, no blood transfusion
Endocrine disorders that cuase anemia
thyroid, adrenal insufficiency
Peyer Patch
lymph node I n gut that underlies mucosa of SI; located by goblet cells. Phacogytose proteins and particles for luminal transport. Determine if food or threat
clinical features of Lead intoxification
personality changess, irritability, headache, weakness, ab pain, vomiting
Underproduction or normla Hb in thalassemia
Small RBC, low hb concentration, uniform RBC, Increased RBC production
Chelation therapy
deferasirox, deferoxamine, deferiprone
Lymphopoiesis
vast majority in Bone Marrow; T cells mature in thymus. Lymphoblast –> lymphocyte
Where in the body is it basic?
CO2 is exhaled in the lungs and leads to increased oxygen affinicity
Pre-B cell
cytoplasmic IgM (light and eavy)
Basophils in Differential
neuclus is obscered by coards, purple, black granules
MCHC
Mean Corpsular Hemoglobin Concentration; avg conc of hg in given volume of red cells
blood in lymph node
entry and exit through hilum
cortex in llymph node
tightly but motile lymphocytes in follicles
HbD
punjab; Beta 121 Glu –> Gln (polar); india, packistan, iran
TLR
bind to initiate inflammatioon cascade and ultimately activate NFkB
how long do nutrophils spend in periphery
less than 10 years, where they are taken out in urine or feces or by monocytes/macrophages
caues of folate deficiency
dietary insufficiency, malabsorption, drugs and toxins, errors in folate metabolism, increased demand, increased metabolism/loss
Bohr Effect
Oxygen is held tightly in basic conditions and released in acidic
Gamma vs Beta Globin
Differs by 39 amino acids; binds to 2-3 BPG poorly, so it is stabalied in R state and shifts curve to left
supportive care, avoid oxidant drugs/food, folate, transfusion if severe
antibodies that cause hemolysis intravascualr and extravascualr
30-50% methemoglobin
moderate depression of CNS, achycardia, tachypnea, shortness of breath
here does heme bind to beta globin
92nd amino acid
Treatment of B12 deficiency
1mg injections weekly/monthly or 2ug orally 2x day
Cooley’s Clinical manifestations
Bone marrow expansion - hair on end, spelenmegaly, osteopenia, iron overlad
igG (classes)
most abundant, passes placent to fetus, longer effect after immunization, half life of three weeks, opsonizing, 2 igG to activate complement
methyltetrahydrofolate
is transferred to liver for sotrage, tissue, and undergoes EHC recycling with jejunum
Spleen anatomy
Red contains phagocytic cells to make RBC and filter RBCs; white: lymphocytes
Risks in splenectomy
sepsis 1) vacciantion before, prophylatic antibiotidies, see doctor if fever above 38.5
Sickle cell trait Concentrations
55-60 A1;3% H2;
Normocytic anemia types
anemia of chronic disease, sickle cell
Polymorphonuclear cells
eosinophils, basophils, neutrophils
Allotypic exclusion
like X inactivation of antibodies, recombination can be done if initial antibody is unsuccessful
Class switching
V domain stays the same, but splicing occurs at DNA level to cut out other constant regions. Cannot go back to the ones cut out
Anemia of Chronic Disease
Chronic infection, chronic inflammation, malignant disease, renal insufficiency, lead intoxification, endocrine disorders
Too few lymphocytes
lymphopenia
Pre-B cell
cytoplasmic IgM (light and eavy)
Lab findings of Chronic infection, inflammation, malignancy
mild/moderate anemia, normochromic/microcytic, dec serum Fe, dec TIBC, normal to increase ferriting, decrease EPO and dec Retic count
Retic count - SCD with B0 Thal
5-30%
Domains in antibodys
made of 7 Beta sheets for rigidity. The region sin between the sheets form the variable regions. Held together by disulfide bonds
laboratory features of renal insufficiency
mod/severe anemia, normochromic, normocytic, EPO dificiency
Neutrophils - immuno
fasts moving and move prominetn cell sin adults 40-60%
Perinuclear hof
golgi in myelocyte
IgE (class)
binds to mast cells and eosinophils, triggers histamine release for allergic reactions; parasite killer
Retic count - SCD
5-30%
Pathophysiology of SCD
hemolysis, increased endothelial-1, proliferation of smooth muscle, increased adhesion, increased platelet activation
Neutrophils - immuno
fasts moving and move prominetn cell sin adults 40-60%
MCH calculation
Hb/RBC count
how type of iron binds to Hb?
Ferrous 2+
Methemoglobin
Ferric form binds to Hb instead of Ferrous. Capacity to carry oxygen is reduced and curve shifts LEFT?
Classical pathway of complement
antigen binds to igG (2) or IgM (1) to activate allosteric change to FC to allow C1q to bind to activate cascate of 1-4-2-3-5-6-7-8-9
Newborn screening SS
FS
Mast cells
Found in tissues rather than peripheral blood, finer granules with one prominent nuclues.
Transfusions
dilute out sickle RBC and provides healthy RBCs
acute anemia, hyperbilirubinemia, hemolysis, reticulocytosis, blister cells, bite cells, heinz bodies
supportive care, avoid oxidant drugs/food, folate, transfusion if severe
where do dendritic cells gather in lymph node
between cortex and paracrotex
where do dendritic cells gather in lymph node
between cortex and paracrotex
Alternative complement pathway
cell wall structures in microbes activate C3 directly in absense of antibody (innate)
Papin
reduces disulfide bonds to create 2 Fab and 1 Fc
Moya Moya fromation in SCD
abnoraml cerebral blood vessesl due to vasculopathy
IL-1
stimualted by chronic infection and inflammation to decrease iron and decrase erythropoietin