Week 1 Flashcards
ATP generation in RBCs is dependent on ______ metabolism.
anaerobic
5 types of white blood cells in order of abundance
Neutrophils Lymphocytes Monocytes Eosinophils Basophils
Function of neutrophils
Finds, ingests (phagocytose), and digests bacteria, cellular debris, and dead tissue
PAMP
Pathogen-associated molecular patterns
- Foreign molecular structures on pathogens recognized by PRRs
DAMP
- Stress/damage indicator molecules from body cells recognized by PRRs
Receptors that recognize PAMPs and DAMPs
Pattern-recognition receptors
(PRR)
EX: TLRs
TLR recognizes foreign pattern-> ______->_______->_______->_______
signaling cascade
NF-KB
expression of chemokines and cytokines
inflammation
Bridge between innate and adaptive immunity
Dendritic cells
Where do dendritic cells predominantly reside?
Interfaces between body and world:
- Skin
- GI tract
- Mucosal membranes
B cells
protect extracellular space (tissue fluid, blood, secretions)
- Recognize antigens via surface receptors
- Secrete antibodies into fluid
- (they DO NOT require the simultaneous recognition of an associated MHC molecule—like T cells)
- Fully differentiated B cell = plasma cell (antibody production factory)
T cell function
Surveys bodys cells
T cell development
produced in bone marrow, mature in thymus
Short ranged mediators produced by T cells
lymphokines
Marker for Helper T cells
CD4
Marker for killer T cells
CD8
Units for Hgb
grams/dl
Reticulocytes circulate __ days in bone marrow and ___ days in blood before maturation
3
1
Reticulocyte count
% of reticulocytes when 1000 RBCs are counted
Normal reference values for reticulocytes
0.4-1.7%
Absolute reticulocytes
% of reticulocytes x RBC count
Reticulocyte Index
measurement of production of RBCs, way to correct reticulocyte count and stress reticulocytes (marrow pushes out immature reticulocytes)
RI
decreased production of reticulocytes → ↓ (RBCs)
RI > 2 with anemia =
loss of RBCs → increase compensatory production of reticulocytes
Hematocrit
a. Proportion of blood by volume made up of red blood cells, value determined by measuring the length of the RBC layer and dividing it by the total length of the column of blood (RBCs+buffy coat+plasma), always reported as percentage
Basic shape and composition of an erythrocyte (5)
- Biconcave disc shape
- Lacks nucleus
- Lacks mitochondria
- Contain lots of hemoglobin
- Membrane is highly elastic
Hematopoiesis
Formation of blood cellular components
Erythropoiesis
process by which RBCs are produced in bone marrow
Hemolysis
RBC destruction
Hemostasis
stopping of bleeding (platelets + endothelium + coagulation proteins)
Thrombosis
Formation of blood clot inside blood vessel that obstructs the flow of blood
Platelets are derived from ____
large cells in the bone marrow called megakaryocytes
1 megakaryocyte = _____ platelets
5000
Leukemia vs lymphoma
a. Leukemia: cancer cells in blood and bone marrow
b. Lymphoma: cancer cells predominantly outside of bone marrow/blood (lymph nodes, lymphoid tissue)
Acute leukemia vs. chronic leukemia
- Acute Leukemia: cells are immature in their degree of differentiation and that clinical course is usually rapid without intervention
- Chronic Leukemia: cells are more mature in their differentiation and the disease follows a more indolent clinical course.
Lymphoid leukemia vs myeloid leukemia
- Lymphoid Leukemia: arising from lymphocytic lineage
- Myeloid Leukemia: arising from one of the other cell types in the marrow
Hemoglobin reference range
14.3- 18.1 g/dL
Hematocrit reference range
39.2-50.2%
RBC reference range
4.76-6.09 x 10*12/L
MCV reference range
80 - 100 fL
MCH reference range
27.5-35.1 pg
MCHC reference range
32.0-36.0 g/dL
Platelet Count reference range
150-400 x 10*9/L
Mean Platelet Volume reference range
9.6-12.8 fL
Red cell distribution width CV reference range
11.7-14.2 %
Red Cell Distribution Width SD reference range
37.1-48.8 fL
WBC reference range
4.0-11.1 x 10*9/L
Neutrophils absolute reference range
1.8-6.6 10*9/L
Lymphocyte absolute reference range
1.0-4.8 10*9/L
Monocytes absolute reference range
0.2-0.9 10*9/L
Eosinophils absolute reference range
0.0-0.4 10*9/L
Basophils absolute reference range
0.0-0.2 10*9/L
NRBC percent reference range
0%
NRBC absolute reference range
0 10*9/L
calculation of MCV using Hct and RBC
MCV = Hct/RBC
Calculation of MCH
Hgb/RBC
Calculation of MCHC
= (Hgb/Hct) x 100
Red blood cell counting and platelet counting
- Impedance Transducer and Histograms
- Blood passes through an aperature, creates change in resistance between electrodes create pulse signals proportional to cell size and platelet volume
- Platelets and RBCs can be counted simultaneously
Flow cytometry
- allows characterization of cells based on DNA/RNA content
i. Make cell membrane permeable, label DNA/RNA with dye, bounce lasers off them, and then look at scattergram
ii. Intensity of fluorescence signal directly proportional to the nucleic acid content of the cell
iii. Measure side fluorescence vs. forward scatter
When is a differential performed?
When requested or flagged by analyzer
Info provided by a differential
- Morphology of RBCs, WBCs, platelets
- abnormally formed elements in the peripheral blood
- relative or absolute quantification of the different WBC populations
Characteristics of RBCs
round, smooth, little variation in diameter, typically not touching/overlapping, central pallor
Characteristics of platelets
small, fine granules
Characteristics of neutrophils
cytoplasm with fine granules, nucleus has clumped chromatin
- Most abundant white cells in blood of adults
Too many neutrophils
Neutrophelia
Too few neutrophils
Neutropenia
Characteristics of lymphocytes
smaller, scant cytoplasm, round nucleus with dense chromatin
i. Absolute lymphocyte count changes as children age (most abundant at age 2-8 years)
Too many lymphocytes
Lymphocytosis
Too few lymphocytes
lymphocytopenia
Monocyte characteristics
normally largest cells, nucleus is irregular and lobulated, amply cytoplasm (gray-blue), irregularly shaped
Too many monocytes
monocytosis
Too few monocytes
monocytopenia
Eosinophil characteristics
bi-lobed nucleus, slightly larger than neutrophils, spherical granules (larger, red-orange)
- count remains constant throughout life
Too many eosinophils
eosinophilia
Basophil characteristics
similar in size to neutrophils, nucleus obscured by purple-black granules, least abundant white cell in peripheral blood
- Count remains constant throughout life
Too many basophils
Basophilia
White blood cell count
total number of white blood cells (neutrophils, lymphocytes, monocytes, basophils and eosinophils) in a microliter or liter of blood.
White blood cell differential
percentage of white cells in an individual that are neutrophils, lymphocytes, monocytes, basophils or eosinophils
Absolute Count DIFF# =
= (DIFF% x WBC) / 100
Speed of innate immune response
Fast
Immature dendritic cells are activated by
cytokines and chemokines
Location of adaptive immune response
in lymphoid tissue NOT periphery
T lymphocytes recognize antigens at ____
antigenic determinant (epitome)
Antigen presenting molecule recognized by T helper cells
MHC Class II
Antigen presenting molecule recognized by Cytotoxic killer T cells
MHC Class I
B cells release ____ to neutralize toxins or prevent binding to target cell
antibodies
Most abundant antibody
IgG
Mechanism of IgG
i.2 adjacent IgG molecules bind an antigen -> cooperate to activate COMPLEMENT, a system of proteins that enhances inflammation and pathogen destruction
First antibody to appear in blood after exposure to new antigen
IgM
Antibody inserted into B cell membranes as their antigen receptor
IgD
Most important antibody in secretions
IgA
Antibody that attaches to mast cells in tissues
IgE
Mechanism of IgE
attaches to mast cells in tissues -> encounters antigen causes mast cell to make prostaglandins, leukotrienes and cytokines, and release its granules which contain mediators of inflammation (like histamine).
Measurements to determine anemia
i. Hemoglobin concentration (g/dL), hematocrit (%) and red blood cell count
ii. MCHC, MCV, Red cell distribution width (RDW), WBC (#cells/vol) + differential, and platelet count (#cells/vol).
iii. RBC morphology via blood smear
iv. Reticulocyte count (%), reticulocyte production index – can use this to look at production of RBC
Reticulocyte count when there is increased RBC production
3.5-5 fold increase from normal range
Stress factors for reticulocyte index: mild, moderate, and severe anemia
- Stress factor = 1.5 (mild anemia), 2.0 (moderate anemia), 2.5 (severe anemia)
Physical exam of anemic patient
vital signs (tachycardia, tachypnea, dyspnea), color of skin (pallor), conjunctiva, lymph nodes, size of liver and spleen, cardiovascular and pulmonary findings.
Symptoms of anemic patient
SOB, fatigue, rapid HR, dizziness, pain with exercise (claudication), angina and pallor
Iron in aqueous solutions
form insoluble hydroxides unless bound (protein, heme, etc.)
Fe salts are more soluble at ____ pH
low
Iron distribution:
- hemoglobin
- myoglobin
- ferritin
- hemosiderin
- enzymes
- Hemoglobin = 65%
- Myoglobin = 6%
- Intracellular Fe storage (Ferritin = 13% + Hemosiderin = 12%) = 25%
- Enzymes = 3.6%
Daily losses of iron
small
- loss from exfoliation of skin and mucosal surfaces (GI, skin); in the urine or with menstruation.
Transferrin
main iron transport protein, 84kDa plasma protein, produced in liver, binds 2 ferric iron (Fe3+) mols for 1 mol protein, high affinity and specificity
Transferrin + iron -> _____->_________
Transferrin + iron -> travels to bone marrow/maturing normoblasts -> binds cell surface receptors, “transferring receptors”
Transferrin- Transferrin receptor complex->
enter bone marrow cell via invagination of clathrin coated pits to form endosome
Endosome becomes acidified (due to H+ entry) ->_____->_____->______
transferrin releases iron -> iron exits endosome via DMT1 transporter -> stored by Ferritin, or used to make Hgb and RBC in circulation
After 120 days, RBCs are _______
removed from circulation by splenic macrophages, releasing iron from heme and stored by ferritin until needed
Location of absorption for iron
duodenum
What maintains solubility and availability of iron until it reaches the duodenum?
gastric pH and gastroferrin
Absorption of non-heme bound iron (5 steps)
a. Enters duodenum as ferric iron and is converted to ferrous iron by surface reductase (mediated by duodenal cytochrome b-like protein - DCYTB).
i. Iron changes valence several times as it passes through cells
b. DMT1: apical ferric iron transporter, divalent (Fe2+) metal iron transporter
c. Ferritin: stores iron in cell, protein coat with iron in middle, can bind up to 4500 Fe molecules
d. Ferroportin: transports ferrous iron across basolateral membrane
e. Hephaestin (a ferroxidase): facilitates basolateral iron export, controls how much ferroportin you have, produced by liver.
What increases iron absorption?
i. Presence of protein (amino acids), vitamin C (maintains iron is appropriate valence state), increased amount of iron presented to the duodenum, increased erythropoietic activity (non-specific increases absorption).
What decreases iron absorption?
Phytates, oxalates and other food constituents (precipitate iron making it less available), decreased amount of iron presented to duodenum.