BL Unit 2 Flashcards
6 types of T cells and functions
5 helper T cells with surface CD4, 1 killer T cell
Th0- undecided precursor; differentiate after dendritic cell presents antigen
Th1- hypersensitivity T cell
secretes INTERFERON GAMMA- pro-inflammatory; M1; chemotactic for monocytes/macrophages
Th17- makes IL-17; resembles Th1 (inflammation); particularly resistant to pathogens
Th2- make IL-4 and IL-3; macrophages are ALTERNATIVELY ACTIVATED or M2; more involved in healing; IL-4 also chemotactic for eosinophils (kill parasites/worms)
Thf- migrate to cortex follicles; help B cells activate into antibody-secreting plasma cells; switch B cells from IgM to IgG/A/E, depending on organ
Treg- suppress all other Th cells; produce TGFbeta and IL-10; very potent
CTL- kill infected cells; lethal hit- signals target to apoptosis
surface markers on T and B cells, and helper vs cytotoxic T cells
B cells: CD20
All T cells: CD3
All Th: CD4
CTL: CD8
cytokines, lymphokines, and chemokines
cytokines- short range mediators made by any cell; affect behavior of same or other cell
IL-1, IL-12
lymphokines- short range mediators made by lymphocytes; subset of cytokine
IFNgamma IL-2,4,5,10
chemokines- small short range mediators made by ay cell; primarily cause inflammation
IL-8, eotaxin
lymphokines made by Th and Treg cells
Th1- IFNgamma and IL-2; pro-inflammatory; attract/activate MI macrophages
Th17- IL-17; attract/activate MIs
Th2- IL-4; pro-inflammatory; attract/activate M2 macrophages
Treg- TGFbeta and IL-10; anti-inflammatory cytokine
describe how Thf and B cells get activated by antigen and switch immunoglobin class
B cell binds its specific epitope and enodcytoses it; the fragments bind to MHC class 2 molecs and move to surface
B cell displays new antigen and Class 2 MHC complex on surface
correct Thf binds and focuses surface interactions and helper lymphokines on B cell
define mitogen and uses for T and B cell mitogens in lab
a. Mitogen: protein that stimulates T cell division
examples of mitogens:
PHA: binds CD3, ConA to stimulate T cell division
PWM: nonspecifically stimulates B and T cell division
effects of mitogen vs antigen when added to normal blood lymphocyte
antigens are specific
mitogens are nonspecific
mitogen- binds CD3 domain to always keep signal on
antigen- binds to antigen-binding site on T cell
antigen receptors on T and B cells
B cells: bind antigen directly with surface antibodies; interact with free antigens
T cells: focus on cell surfaces; only see complexed antigens presented on surface of an identical cell
Antigen Presenting Cells APC
dendritic cells
chop up and display antigens on surface as MHC-antigen complex for recognition by another T cell
Class 2 MHC molecs- when antigens are endocytosed and presented
T cell helpers recognize Class 2
Class 1 MHC molecs- when proteins are synthesized within the cell (not endocytosed);
CTL recognize Class 1
role of T cells in ridding body of viral infection
CTL sees foreign cell (because MHC Class 1 will have it bound); activate target cell to commit suicide through CD95L or lytic granules
Th cells see antigen on dendritic cell, B cell, or macrophage via MHC Class 2; activate immune response and divide
characteristics of T independent antigens
T independent antigens usually have same epitope repeated over and over (common in carbs- streptococcus pneumoniae)
carb chains bind to B cell antibodies; cell activates/divides
response is almost all IgM, so a person deficient in T cells will still make carb antibodies
with protein antigen (rare)- NO IgM or IgG is made without T cell help
experiment where antibody response can be T-dependent
test two leukocyte populations’ ability to make antibodies to the same antigen- 1 with full complement of T and B cells, and 1 with T cells killed by radiation
define Human Major Histocompatibility Complex MHC
distinguish between HLA-A and HLA-B antigens and HLA-D
MHC- group of strongest histocompatibility antigens coded for by a family of genes on a single chromosome
Th- recognize MHC antigens on HLA-D loci (Class 2)
CTL- recognize MHC antigens on HLA-A and HLA-B loci (Class 1)
class 1 vs class 2 histocompatibility antigens
Class 1 antigens- found on all nucleated cells
Class 2 antigens- restricted to B cells, macrophages, dendritic cells, and a few others
define alloantigen and haplotype
alloantigen- part of animal’s self-recognition system (like MHCs)
when injected into another animal, they trigger an immune response aimed at eliminating them
present in some members of a species, but not common to all
haplotype: MHC gene set that you inherited from one parent
Given the HLA‐A, HLA‐B and HLA‐DR phenotypes of 2 parents and their child, work out the 4 haplotypes involved.
Typing at the HLA-A and HLA-B loci can be done by treating the patient’s leukocytes with allele-specific anti-HLA antisera and complement. The most sophisticated labs actually sequence the HLA genes themselves for typing.
D3, B7, A1, etc., are each individual’s haplotypes.
The cells show their phenotypes, the actual proteins expressed on the surface of their cells. Every cell expresses both alleles.
identify the best probable donors of tissues or bone marrow to an individual
good DR match is most important (Class 2)
for Class 1- HLA-A and HLA-B are most important
cells not identical will not stimulate Th1 cells and the huge response; they’ll activate everything else
cells identical at HLA-A and B will not stimulate CTL, but the Th1 cells will still be stimulated and won’t be great
identical twin or sibling is best chance for match
look for bone marrow matches at A, B, C, DR, and DQ
one-way mixed leukocyte reaction (MLR) and its use
cells from donor are treated to prevent their division (via DNA synthesis inhibitors/radiation)
observe recipient’s Th cells dividing in response to donor’s HLA-D (mostly DR)
a strong rxn may preclude doing the transplant
distinguish between HLA-D and DR, DP, DQ
HLA-D is general term for group of loci that give rise to MHC type 2 antigen-presenting proteins
DR, DP, DQ- individual loci within the D region of Chromosome 6
interaction of T cells recognizing antigen plus HLA-D and A/B in graft patient
Th are programmed to recognize HLA-D (class 2)
CTL recognize HLA-A and B (Class 1)
rejection: dendritic and macrophage cells from graft move to host lymph node; host Th1 cells recognize foreign HLA-D and synthesize lymphokines and up regulate cell-surface receptors for GFs like IL-2; Th1 also will secrete IFNgamma that attract M1 macrophage inflammation
CTL- recognize foreign HLA-A and B, but also require Th1-derived IL’s as a second signal for activation; once activated, highly cytotoxic and may proliferate
similar to virus, except:
normal response: peptide plus self-MHC recognition
rejection: foreign MHC recognition
cellular and molecular events of a graft rejection- normal and hyperacute
most important mech is via CTL and Th1 cells (via lymphokines and monocyte/macrophage inflammatory response)
normal rejection: Th1 cells are activated by “almost me” MHC type 2’s; activate Th2 cells, which activate B cells to produce antibody against graft; and CTL attach tissue directly once they bind to MHC type 1s
Th1 also brings other inflammatory cytokines, like TNF-alpha (tissue necrosis factor)
hyperacute rejection: graft tissue rejected immediately- stays white/bloodless even after reperfusion
- there was a circulating antibody against the graft from a previous/failed graft or against graft’s residual blood
- antibodies attach to endothelium, activate lots of complement, set off anaphylatoxin release (C3a, C4a, C5a) from mast cells; leads to vasospasm and tissue ischemia; can lead to systemic inflammation
- T-cell mediated rejection is slower than complement-mediated
- always cross-type the ABO blood antigens from donor and recipient
- immunosuppressants are typically given for a lifetime after a transplant
how T cells recognize “self + x” and foreign MHC (allorecognition)
receptors are selected to recognize “self + x”
recognition of foreign MHC is a “chance” cross-reaction
5% of T cells will bind a foreign MHC strong enough to cause activation
can’t give other people T-cells because MHCs are different and T cells are specifically selected for an MHC
example of disease whose incidence is tightly linked to a particular HLA allele and its mech
ankylosing sponditis- involves chronic inflammation and eventual calcification of the insertions of tendons into bones
95% of people w/ this have a specific HLA-B allele that will also disease rats
-price to pay for genetic variability in HLA region- eventually it’s going to look similar to an antigen and you’ll develop an autoimmune response to own tissues
also HLA-linked cases of diabetes, lupus, and kidney/lung degenerative disorder
basic structure and general movement of lymph and lymphocytes through a lymph node
lymph circulates to lymph node via afferent lymphatic vessels and drains into node just beneath capsule called sub scapular sinus
subcapscullar sinus drains into trabecular sinuses then to medullary sinuses
sinus space is criss-crossed by pseudopods of macrophages, which filter lymph
medullary sinuses converge at hilum and leave via efferent lymphatic vessel
ultimately drain to central venous subclavian blood vessel via post-capillary venules; cross wall via diapedesis
activated vs non-activated nodules
germinal center differentiates the two germinal centers- sites within lymph nodes/nodules in peripheral lymph where mature B cells proliferate and class switch
vasculature of lymph nodes
blood supply enters through small artery in hilum
branches repeatedly to entire node
specially lined with HIGH ENDOTHELIAL VENULE- site of diapedesis of lymphocytes from blood to lymph node
-allows you to populate all nearby lymph nodes rapidly during an infection
leaves via small vein
blood flow through thymus
small arteries enter thymus through outer capsule and penetrate into thymus
bifurcate within the CT septa between lobules
vessels’ cells have tight junctions, and surround by endothelioreticular cells- forms blood-thymus barrier for developing thymocytes
efferent lymphatics also travel in the septum
thymus blood flow and thymus lymph fluid flow
blood- everywhere, blood flow in via arteries, out via veins
pierce capsule; trebeculae; cortex; everywhere (incl medulla)
lymph flow- none coming in.
efferent lymphatic drain lymph fluid (and veins) outwards
NO afferent lymphatic to thymus
nuclei and cell bodies of reticuloendothelial cells in thymus and Hassall’s corpuscles
involved in selection process for thymocytes as they progress toward medulla; provide microenvironment to protect maturing thymocytes
Hassall’s corpuscles: cells that thickly populate medulla; produce lymphokines that promote thymocyte maturation into adult T cells
blood flow through spleen
open blood circulation through porous splenic sinuses
receives blood via splenic artery
branches into central arterioles into the red pulp
lined with discontinuous endothelial cells where RBCs, WBCs, and platelets exit to enter sinuses
Periarteriolar lymphoid sheath (PALS): sheath around central arterioles; WHITE PULP; germinal centers within these sheaths
drained via splenic vein
only has efferent lymph vessels (like thymus), which leave from hilum
cell components of red and white pulp
red pulp: 75% of spleen; RBC rich with loose sinuses; filters blood, antigens, microorganisms, and old RBCs
white pulp: organized lymph tissue
contains T cells, B cells, accessory cells; mount an immune response to antigens in blood; present in form of PALS, containing B cell follicles and T cells
regions of mucosal-associated lymphoid tissue
tonsils (palatine, lingual and pharyngeal (adenoids), esophageal nodules, appendix, bronchial nodules, large aggregation of lymphocytes in intestine,
colon: abundant nodules both in mucosa and submucosa known as Peyer’s patches
function and distribution of lymph system
cleanse blood and lymph and provide adaptive immunity
produces and stores agranular WBCs or lymphocytes
4 forms of lymph tissue: non-encapsulated aggregates of lymphocytes lymph nodes thymus spleen
these are composed of free lymphocytes and a supporting framework of reticular cells
types of lymphoid cells
helper T cells (5 kinds)
- help B cells
- express CD3 and CD4
- recognize MHC Class 2
CTL
- express CD3 and CD8
- recognize MHC Class 1
B cells
express CD20
structure of all major lymph organs
lymph nodes- small; found all over individually or clustered; non-specific filters of debris/microorganisms; site of antigen presentation in adaptive immunity
lymphocyte enters small lymphatic vessel; connects to afferent lymphatic vessel; enters node into sub capsular space
thymus gland- bilobed thymus with CT capsule where trabeculae divide organ into pseudo lobes, where all thymocytic cells develop to release mature T cells
-lymphocyte mass in thymus decreases through childhood
NO reticular fibers
stromal cells provide support
Hassall’s corpuscles: circular layer of reticular cells in medulla to suppress autoimmune events
CORTEX: densely packed developing thymocytes
MEDULLA: more mature thymocytes, less dense
thymocytes leave via lymphatics and blood vessels
spleen: multi purpose lymphoid organ; role in adaptive immunity
MALT: mucosal-associated lymphoid tissue
unencapsulated collections of lymph cells and associated support cells to encounter antigens passing through mucosa
-tonsils, appendix, nodules, Peyer’s patches in intestine
-M cells deliver antigen to underlying lymph tissue for adaptive immune response in intestine
primary vs secondary lymph organs
primary: bone marrow and thymus
major sites of development of B and T cells
secondary: seeded with cells from primary tissues (GALT, Peyers patches, etc)
encapsulated lymph organs
lymph nodes
spleen
thymus
humoral immunity and cell-mediated immunity
humoral immunity may prevent a viral illness, but T cell immunity is necessary for recovery
- antibody maybe prevent virus from establishing an infection
- once the infection takes place, you need to kill infected cells before virus multipilies
define local immunity
local immunity on the surface that is being invaded can prevent the invasion- secretory IgA
Sabin (attenuated, live, oral) polio vaccine was so effective- those immunized had high levels of IgA in their secretions and didn’t get colonized by real virus
organisms against which cell-mediated immunity is most effective
viruses, fungi, yeasts, intracellular bac
organisms against which humoral immunity is most effective
extracellular bac and pathogens
human and animal antitoxin
killed virus vaccine
live virus vaccine
longest immunity
human: IgG against tetanus
antimal: IgG against tetanus
practical difference: IgG solns tend to aggregate when they sit around
humans- causes lots of complement activation (pain, inflammation, etc) due to proximity of bound IgG antibodies
animal- less complement is activated due to inter-species antibodies not activating each other’s complement very well
killed vaccine: injected polio (Sabin) vaccine
live vaccine: oral polio (Sabin) vaccine
longest immunity tends to be live vaccines because body produces MHC Class 2 AND 1 responses from your own, infected cells
children immunizations for
diphtheria, pertussis, tetanus
polio
measles
diphtheria, pertussis, tetanus: 15-18 months
polio: 2 mo, 4 mo, 6-18 mo, 4-6 years
measles: 12-15 mo, 4 years
live viral vaccines tend to be ineffective in young; destroyed by mother’s circulating IgG before the child develops the antibody
IgG and IgM titers in diagnosing infections
IgM- made quickly and goes away quickly, so gives good idea if kid has had a disease recently
IgG- measure several times to determine increase/decrease; have they already been sick and made them, or are they just now getting sick?; mother’s IgG in utero
polio vaccines- oral and parenteral
in US: parenteral polio vaccine used
-is a killed (Salk) vaccine; because some kids with weak immune sys’s might get sick from exposure to the live Sabin virus, given oral
oral is easier to distribute, esp in healthcare access problems
- transmissable- immunized kid can spread attenuated virus and spread protection
- can cause polio in immunocompromised kids
define herd immunity
proportion of a given population that has immunity against a particular infection
commonly expressed as percentage
morphologic features of monocytes and tissue macrophages
blue/purple stain with u-shaped nucleus
derived from myeloid/monocyte precursor under stimulation of GM-CSF and M-CSF
develop in bone marrow for 7 days then move to peripheral blood for 3-5 days; some emigrate to tissues
turnover: days-months
major funcs: migrate to sites of infection and remove microbes, dead/dying inflammatory cells/debris; filter microbes from blood stream (spleen); process and present antigens to adaptive immune sys; remove apoptotic cells
morphologic features of eosinophils
RED cytoplasm and bi-lobed nucleus
produced in bone marrow from IL-5
move to peripheral blood then mucosal surfaces (GI tract, tracheobronchial tree, etc)
turnover: weeks
can play a role in allergic reactions, parasitic infections, and response to tumors
can be phagocytic and immunostimulatory or inhibitory
morphology of basophil
prominent blue-purple primary granules
produced in bone marrow
receptors for IgE and appear to play major role in hypersensitivity (allergic) reactions
neutropenia and clinical consequences
decrease in absolute neutrophil count (bands and sets) below accepted norms
adults less than 1500 is bad; newborns less than 3000 is bad
risk for infection
acquired and congenital causes of neutropenia
acquired:
chemotherapy drugs
viral infections (EBV, measles, CMV, hepatitis, HIV)
nutritional deficiencies: folate, B12, copper, protein/calorie
congenital:
Kostman Syndrome- severe peripheral neutropenia + decrease in myeloid production
-high risk for infection and death before age 2 w/o aggressive treatment; ARREST in neutrophil development
Schwachmai-Diamond Syndorme- neutropenia, pancreatic insufficiency (fat malabsorption, bone abnormalities, growth delay); 1/2 develop aplastic anemia or MDS/leukemia; may die early from bone marrow defect; APOPTOSIS of neutrophil precursors
cyclic neutropenia- severe neutropenia (5-7 days) with periodicity (15-25 day cycles); low ANC= mouth ulcers
chronic idiopathic neutropenia: from myeloid hypoplasia and maturation arrest
increased turnover in neutrophils
chronic benign neutropenia of childhood- no risk of infection; resolves after mo 20
autoimmune neutropenia
alloimmune neutropenia- mother’s Ab’s attack baby’s neutrophils
splenomegaly and hypersplenism
severe infection- activate C5a- excessive killing of neutrophil that have eaten bugs
major treatment strategies for neutropenia
broad spectrum antibiotics then specific antibiotics if infection can be identified
granulocyte colony stimulating factor (G-CSF) to normalize production of neutrophils
some antibody mediated syndromes may response to IV gamma-globulin IVIG
define leukocytosis
left shift
increase in total WBC count
think infection, inflammation, non-specific physiologic stress, malignancy/leukemia
left shift- changes in WBC differential with increase in sets and bands and possibly some immature myeloid precursors usually only found in marrow (metamyelocytes of myelocytes)
basophilia
increase in basophils
primarily seen in drug or food hypersensitivity or urticaria; also in infection/inflammation (rheumatoid arthritis, ulcerative colitis, influenza, chickenpox, smallpox, tuberculosis) as well as myeloproliferative diseases (CML, myeloid metaplasia)
eosinophilia
drugs, bugs, allergies
allergies/allergic disorders (asthma, hay fever, hives, etc), parasitic infections, drug rxns,
more rare: pemphigus, tumors/malignancies, other infections
monocytosis
lymphomas, infection, and collagen disease
may be found in hematologic (pre) malignancies (AML, pre-leukemia states, lymphoma, Hodgkin’s), collagen vascular disease (SLE, RA), granulomatous disease (sarcoid, ulcerative colitis, Crohn’s), infection (subacute bacterial endocarditis, syphilis, tuberculosis), and carcinoma
normal functions of neutrophils
Adhesion: CD11b and CD18
Ingestion: CD11b to ingest microbe
move in laminar flow of blood but are pulled into infected areas via rolling motions with endothelial cells; then firm adhesion with adhesion proteins; then diapedesis through cell junctions; move toward offending organisms via chemotaxis; following chemoattractants (like bac products, C5a, cytokines, chemokines) up the conc gradient to engage the invader
at site of infection: microbe has been opsonized with C3b or antibody and is enveloped by several fusing pseudopods, forming a phagosome; eventually initiate respiratory burst and from ROS
ROS and oxygen-independent mech’s are focused on the phagolysosome and lead to death/dissolution of microbe
neutrophil dysfunctions
LAD 1, LAD 2, Actin disfunction specific granulocyte deficiency myeloperoxidase deficiency chediak-Higashi syndrome chronic granulomatous disease
Leukocyte adhesion deficiency I: CD18 deficiency; dec adherence to endothelial surface- neutrophilia; lack CD18, recurrent soft tissue infections like gingivitis, cellulitis, abscesses, delayed umbilical cord separation
LADII: abnormal Sialyl LeX prevents adhesion to selections- neutrophilia;
both LAD 1 and 2 have recurrent infection issues with wound healing; decreased adherence, mental impairment, short stature, bombay phenotype
actin dysfunction: impaired chemotaxis and ingestion; recurrent infection; defect in actin assembly
specific granule deficiency- diminished chemotaxis and bacterial killing= recurrent infections; can’t make granule proteins
myeloperoxidase deficiency- impaired fungal killing when diabetes is present too; packaging defect in processing of granules; can’t kill CANDIDA
Chediak-Higashi syndrome- granule defects - leak + big, defects in movement + degranulation and microbicidal activity; oculocutaneous albinism, photophobia, fever, hepatosplenomegaly, neurodegenerative; don’t get rid of granules well–> large granules
chronic granulomatous disease- absence of respiratory burst and production of ROS; defects in one of 4 oxidase components, so no toxic oxygen metabolites are produced; can’t kill COAGULASE + bacteria/fungus; defect in gp91phox
NADPH oxidase enzyme system
composed of 6 or more proteins distributed in plasma membrane or specific granule membrane or in cytosol
with a phagocytic stimulus, assembly of the cytosolic components with the membrane components assembles the system and results in activity with addition of an electron to oxygen to form supersede anion from which H2O2 and other ROS can rapidly be formed
uses and electron from NADPH
lab testing:
DHR: if you have oxidative burst-fluorescence, measure oxygen power
NBT dye reduction, lets for CGD: the higher the blue score the better it is at making ROS
defect evidenced by failure to reduce NBT dye, oxidize dihydrohodamine, or produce O2
defect impairs bactericidal activity
characterize infections with defects in phagocytes or complement
phagocytes:
high bac and fungal infections
infections w/ atypical or unusual microorganisms
catalase positive organisms in patients with CGD
infections of exceptional severity
periodontal disease in childhood
recurrent infections where body has interface w/ microbial world
cellulitis, perianal
complement:
bac infections which might be seen w/ antibody deficiency
terminal complement deficiencies (C5-C9) have problems with Neisseria**
C3-recurrent bacterial infection
C1, C2, C4-SLE, autoimmune, inflammtion
screening and confirmatory tests for phagocyte problem
screening: CBC, differential Review of morphology Bactericidal activity Chemotaxis assay Expression of CD11b/CD18 NBT dye reduction or DHR oxidation.
confirmatory:
Adherence to inert surface or endothelial cells. Measurement of CD11b/CD18, L-selection, Sialyl LeX.
Response to chemoattractants: shape change, change in direction, rate of movement. Actin assembly. Ingestion of labeled particles or bacteria. Degranulation of specific and azurophilic components.
Bactericidal/candidicidal activity. Production of O2-, H2O2 other oxidants. Studies for specific molecular defects in oxidase or other cell constituents.
screening and confirmatory tests for complement problem
screening:
C3-most common, CH50-total pathway
Quantitative Ig’s, Lymphocyte numbers
confirmatory:
Measurement of specific complement components: alternative and classical pathways.
Detailed evaluation of adaptive immune response.
management strategies for patients with innate immune disorders
anticipation of infection; aggressive attempt to identify cause
surgical procedures for infected sites
prompt imitation of broad spectrum antibiotics then switching to specific when identified
G-CSF doses for severe quantitative neutropenia
prophylactic antibiotics or cytokine therapy (INFgamma for CGD) for specific neutrophil dysfunctions
Transplant with hematopoietic stem cells to reconstitute neutrophil numbers/func
gene therapy: still a lot of problems to be resolved before it’s a practical solution
liver disease- suggestive of
macrocytic anemia
small MCV means you should get
Hemoglobin electrophoresis
thalassemia traits with hemoglobin levels
alpha thal trait- normal Hb
alpha thal intermedia- only 1 working alpha; don’t need iron therapy; worry about hydrops fetalis
beta thalassemia major- low/no Hb H (4 beta chains)
Hb H made of
seen in
4 beta chains
seen in alpha thalassemia problems
chronic transfusion therapy
needed only if patient is symptomatic
folic acid treatment
for people who turn over RBCs quickly- hemolytic problems
splenectomy treatment
controversial
not recommended unless someone is really having trouble with hemolysis
bone marrow transplant treatment
for severe beta thalassemia
alpha genes missing
1 missing- trivial microcytosis
2 missing- microcytic
3 missing- intermedia
4 missing- hydrops fetalis
Hb E
common in SE Asia
most common thal on West coast
structural variant of Beta globin
-potential for beta thalassemia
HbEE patients- mild hemolytic anemia and splenomegaly
HbE trait- asymptomatic, but maybe low MCV
pancytopenia
anisocytosis
pancytopenia- reduction in RBC, WBC, and platelets
anisocytosis- unusual shape; high RDW
increased RBC destruction seen with
high retic count
test EPO when you suspect
kidney disease
want to see iron levels when
MCV is low, like when surgeon gives patient a lot of blood
want to see (high) LDH numbers when
suspect hemolysis
or 3-4 days post myocardial infarction
high TIBC
low iron
low ferritin
suggests
iron deficiency anemia
low/nl TIBC
low/nl iron
nl/high ferritin
suggests
inflammation
chronic disease
thalassemia
low Vit B12 suggests
macrocytic anemia
low TIBC doesn’t suggest
low TIBC and normal serum ferritin suggests
iron deficiency
chronic inflammation
FE/TIBC levels below 10% mens
over 50% mens
iron deficiency
iron overload
serum creatinine high suggests
kidney function is bad; moderate-chronic kidney disease
EPO levels aren’t very helpful in mild anemia
EPO injections might help
high TIBC indicates
non-response to EPO injections due to
decreased iron stores
lack of iron stores
EPO levels are ___ in iron deficiency anemia than anemia of chronic disease
higher
EPO is released from kidney in response to
tissue hypoxia
when you treat with EPO injections
MCV changes
retic count goes up; that’s normal
if MCV falls to 77fL, treat with iron tablets because you’re making blood but MCV is falling because you’re iron deficient
if MCV goes up to 95, that’s normal because retic is going up; don’t think they have folate deficiency
polycythemia if hypoxia is present Hct >52%
usually improved quality of life; but other risk:benefit ratios
high MCV suggests
folate deficiency
normocytic anemia potential diagnoses:
sickle cell
renal failure associated anemia
autoimmune hemolytic anemia
NOT iron deficiency anemia (microcytic)
cytochrome B function
converts ferric to ferrous iron
able to absorb ferrous iron
dacryocytes
anisocytosis
polychromasia
spherocytes
teardrop shaped cells
variation in size
blueish cells,; premature retics being released
spheres; no central palor
spherocytic anemia
most concerned about DAT level
want a direct Coombs test
want retic count
haptoglobin
high retic count suggests:
sickle cell
recovery from acute severe GI bleed
hemolysis
NOT iron deficiency
postive Coombs test tells you
it’s autoimmune disorder
spherocytes- associated with warm antibody autoimmune hemolytic anemia
cold agglutinin is usually
IgM and intravascular;
C3?
warm agglutinin is usually
extravascular, mostly in spleen, so you recycle iron, not lose it
low retic count with higher Hct shows successful treatment
when abnormally high retic count falls, the MCV falls, because the retics are big
possible cause of thrombocytopenia
antibody coating of platelets
don’t think hemolytic anemia is relapsing if retic count is mostly normal
typically not from folate deficiency
in most autoimmune hemolytic anemias, you see
high WBCs and platelets
hypochromic
hyperchromic
pale central palor, sometimes cells break when smeared
dark central palor- no transparency
melana
black, tarry stools
bleeding lowers your iron stores
aplastic
not making any RBCs
patient with active hemolytic anemia at risk for
folate deficiency
but presence of iron in marrow means it isn’t deficient
high methylmalonic acid indicates
low B12
differentiates B12 vs folate deficiency
high homocysteine indicates
either B12 or folate deficiency
