Week 5 (exam 2) Flashcards
What is the purpose of genetic testing?
used to IDENTIFY PREDISPOSITION to a disease
done in CONJUNCTION WITH obtaining a detailed FAMILY HISTORY
ASSIST in determining if PREVENTATIVE MEDICINE OR SURGERY is needed
What are the examples of genetic testing
Predictive Testing
- BRCA testing
Diagnostic Testing
- HLA B27
Carrier Testing
- CF gene
pharmacogenetic testing
- medications for depression
- if multiple medications are not working
Define predictive testing
tells if a person is carrying a mutation that will cause or put the patient at higher risk for a disease later in life
- ex: BRCA testing
knowledge of a predictive disease can change patient behavior or clinical intervention
- suicide, lifestyle modifications
What are some disadvantages of genetic testing
financial discrimination
- some health insurances don’t cover
expensive
- not covered by insurance
information
- may cause anxiety/increased emotions
What is not a reliable proxy for genetic difference
race
What is more predictive than race in determining influence on health
geographic ancestry
Define race
refers to a group sharing outward physical characteristics and some commonalities of culture and history
- ex: skin color, hair texture, height/build
Define ethnicity
markers acquired from the group with which one shares cultural, traditional, and familial bonds
- ex: behaviors, cultural expression
When would you order genetic screening?
based on ethnicity (not race) and family history
- geographic location is best
Examples:
inherited (thalassemia –> Africa, SE Asia, Central American, Mediterranean)
sickle cell disease (Africa, SE Asia, Central American, Mediterranean)
cystic fibrosis (European, eastern European Jewish)
spinal muscular atrophy (varies greatly based on ethnic background)
tay sachs (eastern European Jewish)
What is PCR
fast, inexpensive techniques used to amplify (copy) small segments of DNA
What are the indications for PCR
when DNA sample is small/limited
- common ex: COVID test
What are the methods of PCR
sample is heated –> DNA denatures into single-stranded DNA
taq polymerase (enzyme) builds two new strands of DNA using original strains
What are examples of PCR
DNA fingerprinting
detecting viruses and bacteria
- influenza, covid, aids
genetic disorders
- aneuploidy, muscular dystrophy, prenatal screenings
cancers
What is blot testing
when a macromolecule (DNA, RNA, protein) is resolved in a gel matrix, transferred to a solid support, and detected with a specific probe
What are the types of blot testing
southern blots
- DNAs are transferred to paper and specific nucleotide sequences are detected
northern blots
- RNAs are transferred to paper and specific nucleotide sequences are detected
western blots
-proteins are transferred to paper and specific nucleotide sequences are detected
What are the indications for blot testing
western: to detect HIV or LYME
southern: to analyze DNA sequences or genome
- forensic and paternity testing
northern: to detect gene expression
- most expensive
SNOW DROP
S&D: southern&dna
N&R: northern&RNA
O&O: O
W&P: western&protein
What is flow cytometry
lab technique to assess size, granularity and protein expression of an individual cell
What are the indications for flow cytometry
staging/cell types of acute leukemias
HIV monitoring
Rh isoimmunization
detection of CD34+ stem cells
NOT IN RED:
reticulocyte counting
detection of autoantibodies
T-cell cross-matching for transplant
- recipient vs donor
What is ELISA
enzyme linked immunosorbant assay
immunologic test used to detect the presence of either a specific antigen (HBsAg) or antibody (anti-HBs) in a patient’s blood
- detection involves the use of antibody linked to an enzyme
What are the indications for ELISA
viral testing (influenza, ebola, west nile, HIV), lyme, RMSf
- RMSF: rocky mountain spotted fever
- first line testing for HIV
- blood borne viruses (HBV, HCV, HIV)
bacterial testing
NOT IN RED:
home pregnancy tests, food allergies, hemolytic anemia
Explain karyotyping
analysis of chromosomes
- size, shape, and number of chromosomes
a photograph of the complete diploid set of chromosomes
- grouped in pairs
- descending in size
What are the methods of karyotyping
blood test
bone aspiration/bx
amniocentesis
CVS (chorionic villus sample)
- placenta while baby is in utero
Examples of conditions seen in karyotyping
down syndromes
trisomies
turner syndrome
- missing an X chromosome
What is FISH
one method for localizing a piece of DNA within a genome
- fluorescent DNA/RNA probe binds to specific gene site of interest on chromosomes
What are the indications for FISH
used for specific localization of genes and direct visualization of chromosomal anomalies at the molecular level
- microdeletion
- translocation
- duplication
What is a microarray
a laboratory tool used to detect the expression of thousands of genes at the same time
- whether the DNA from a particular individual contains a mutation in genes
- expensive
What are the indications for a microarray
classification of tumors
identification of target genes of tumor suppressors
identification of cancer biomarkers
identification of genes associated with chemoresistance
NOT IN RED
identification of SNPs and mutations
drug discovery
What are the methods of a microarray
high throughput dot blot for man mutation testing at once
What are the indications for cfDNA
screening for trisomy and other chromosomal disorders of the fetus/baby
identification of sex
What is cfDNA
cell-free DNA screening
pre-natal blood test for pregnant women
- some of the unborn fetus DNA circulates in the mother’s bloodstream
What is the method for cfDNA
blood test at or above 10 weeks
What makes cfDNA less effective
pregnancy with multiples
BMI>30
pregnant via donor egg
<10 weeks pregnant
on blood thinners
What is stool DNA testing
noninvasive lab test that identifies DNA changes in the cells of a stool sample
DOES NOT REPLACE A COLONOSCOPY
What are the indications for stool testing
screening should start at age 45
- if family hx, at least 5 years prior to when family members had it
often detects the presence of colon cancer
What is the method for stool testing
cologuard
- looks at genes related to CRC
- 90% sensitive
What are the three non-invasive colorectal cancer screenings
- fecal occult blood test (FOBT-Heme)
- limited by intermittent bleeding
- requires 3 stool samples
- dietary restrictions - fecal immunochemical test (FIT-globin protein)
- limited by intermittent bleeding
- single stool specimen
- no dietary restrictions - stool DNA
- precancerous/cancerous cells continuously exfoliated
- single stool specimen
- no dietary restrictions
What is CBC
blood test that is used to evaluate overall health
- give important info about WBC, RBC and platelets
can aid in diagnosing conditions
- anemia, infection, leukemia
can help with disease staging
- leukemia
assist in the evaluation of symptoms
- weakness, fatigue, fever, bruising, etc
What are the components of CBC
WBC (with differential)
HgB (hemoglobin)
Hct (hematocrit)
Plt (platelets)
RBC
RBC indices
- measure the size and hemoglobin content of RBC
What are the formed elements of blood
RBC
WBC
platelets
Define leukocyte
WBC
Define granulocyte
WBC with secretory granules in cytoplasm
- neutrophil, basophil, eosinophil
Define nongranulocyte
mononuclear WBC
- lymphocyte, monocyte
Define leukocytosis
increased WBC count (>10,000)
Define leukopenia
decreased total WBC count (<4,000)
Define polymorphonuclear leukocytosis (PMNs/polys)
another name for neutrophils
Define phagocytosis
killing and digestion of bacterial microorganisms
What is the major function of WBC
fight infection
- react against foreign bodies or tissues
What does an increase in total WBC count mean
infection
malignancy
leukemia
etc
*bacteria increases WBC
What does a decrease in WBC mean
bone marrow failure
drug toxicity
autoimmune disease
viral disease
*virus decreases WBC
What are the 2 components of WBC
total number
differential count
What does the differential count for WBC do/help
measures the percentage of each type of leukocyte present in the same specimen
increased WBC tells you there is an infection, the differential can help narrow down cause of infection
What are the critical values of WBC
<2000 OR >40,000
What are the factors that can interfere with WBC results
exercise
- decreases
stress
- increases
h/o splenectomy
- increases
time
- lower in AM and increase in PM
age
- in order pts, WBC will be increased in an active infection
certain drugs
What is the main cause of leukocytosis
What are other causes
the main cause of an increase in WBC (>10,000) is an infection
leukemia
other myeloproliferative disorders
- systemic mastocytosis
- eosinophilia
other malignancies
trauma/stress/hemorrhage
tissue necrosis
inflammation
dehydration
steroid use
What is the main cause of leukopenia
What are other causes
the main cause of a decrease in WBC (<4000) is drug toxicity
- cytotoxic chemotherapy
bone marrow failure
sepsis (end stage)
- body trying to so hard to defeat infection, stores become depleted
dietary deficiencies
autoimmune disease
hypersplenism
Describe neutrophils
- most common granulocyte
- primary function; phagocytosis
- multilobulated nuclei
- produced in 7-14 days and only live for 6 hours
*** seen in bacterial infection and trauma
— results in elevated WBC - immature form called band cells
- when neutrophil production significantly stimulated, these immature forms leak into circulation (aka left shift)
Define absolute neutrophil count (ANC)
WBC x (% neutrophils + % bands) / 100
helps determine patients real risk of infection
ANC less than 1000 may need to consider protective isolation
Describe neutrophilia
increased neutrophil count
associated with: increased production, increased marrow release, and defective margination
most important acute cause is infection
Describe neutropenia
decreased neutrophil count
associated with: depressed production, increased peripheral destruction, excessive peripheral pooling
common causes: myelotoxic drugs (drug therapy/chemotherapy), aplastic anemia, viral infections
What is a major consequence of neutropenia for a patient?
infection
viral infection caused a decrease in WBC –> easy for bacterial infection to come in
Describe eosinophils
involved in allergic reactions
- amount increases as allergic reaction increases
releases histamine
does NOT respond to bacterial and viral infections
What are the common causes of eosinophilia
- parasitic infections
- allergic reactions
- adrenal insufficiency
- inflammatory/immune
What are the common causes of eosinopenia
corticosteroid treatment
- steroid suppression of WBC
Describe basophils
rarest of granulocytes
similar to tissue mast cells
cytoplasm contains heparin, histamine, serotonin
involved in allergic reactions
- dont respond to bacterial or viral infections
infiltrate tissue involved in allergic reaction and further the inflammatory reaction
reaction decreases, count decreases
What are the common causes of basophilia
hypothyroidism
splenectomy
What are the common causes of basopenia
hyperthyroidism
pregnancy
drugs:
- chemotherapy
- glucocorticoids
Describe lymphocytes
nongranulocyte
primary function: fight chronic bacterial and acute viral infections
2 types:
- B cells
- T cells
* differential count does not differentiate between B cells and T cells
Describe B cells
involved in humoral immunity
directed toward extracellular pathogens
produce antibodies that bind to antigens
mature in bone marrow
Describe T cells
AKA killer cells, suppressor cells, T4 helper cells
directed toward intracellular pathogens
do NOT involve antibodies
mature in thymus
What are the common causes of lymphocytosis
chronic bacterial infection (TB)
viral infection (Mumps, rubella, and pneumonia)
infectious mononucleosis, infectious hepatitis, cholera, brucellosis, syphilis, toxoplasmosis
pertussis
What are the common causes of lymphocytopenia
HIV
- acute viral infection
idiopathic causes, chronic HIV, drugs, corticosteroids, radiation therapy, and cancer therapy
causes (neoplastics): carcinoma, lymphoma
Describe monocytes
devleop from monoblass
nongranulocyte
phagocytes
produce interferon
produced more rapidly and longer time in circulation
- difference between neutrophils
What are the common causes of monocytosis
bacterial infections
viral infections
- monoculosis
inflammatory conditions
protozoal infections
- malaria
rickettsial disorders
What are the common causes of monocytopenia
HIV, aplastic anemia, hairy cell leukemia, drug therapy (steroids –> prednisone)
Write out the Leukemia chart (slide 43)
Define RBC count
the number of circulating rbc in 1mm3 of peripheral venous blood
lives in the blood circulation for 120 days (4 months)
at end of life, rbc is lysed and extracted from circulation by spleen
What increases RBC production
erythropoietin is secreted by the kidneys, which increases RBC production
What decreases RBC count
pregnancy
- normal body fluid increases, resulting in dilutional decreased RBC
- nutritional deficiency
drugs
- meds that decrease marrow production
- meds that cause hemolysis
What increases RBC count
living in high altitudes
- low O2, produce more rbc to compensate
dehydration
- concentrated
drugs
- erythropoietin, gentamicin
Patients with low RBC value are said to be
anemic
What is the most common cause of decreased RBC count
anemia
Describe erythrocytosis
high RBC value
body requires need for greater O2 carrying capacity
What is another cause of erythrocytosis
secondary to illness
COPD
severe dehydration
hemoglobinopathies
What is a reticulocyte count
blood test that measures how fast immature rbc are made by the bone marrow and released into the blood
in the blood for 2 DAYS before maturing into rbc
What do Hgb (hemoglobins) do
Hgb is a protein molecule found in rbc that carries oxygen from the lungs to the rest of the body
What is the importance of Hgb
vehicle oxygen transport throughout circulation
- low Hgb = not able to carry as much O2 to body
What are the critical values of Hgb
less than 7 or above 21
What are the interfering factors of Hgb
pregnancy - slight decrease
values highest in the AM and lower in the PM
heavy smokers have higher Hgb levels
living in high attitudes
drugs
If Hgb is critically low, what are we at risk for
fainting, angina (chest pain), myocardial infarction, cardio heart failure, and stroke
If Hgb is too high/much, what are we at risk for
intravascular sludging this leads to a stoke and other organ infarction
- due to being backed up, oxygen/blood doesn’t get delivered to specific sites
What is Hct
Indirect measure of RBC number and volume
measures % of total blood volume made up of RBC
Write out the red cell indices chart (slide 74)
define -cytic
refers to size
define -chromic
refers to color
What are interfering factors for red cell indices
abnormal RBC size
increased WBC
elevation in lipid levels
Define mean corpuscular volume
measures the average volume/size of a single RBC
- used to classify anemias
What does increased MCV mean
macrocytic
abnormally large rbc size
What does decreased MCV mean
microcytic
abnormally small rbc size
What causes macrocytic anemia
vitamin B12
folate deficiency (most common cause)
What increases MCV
pernicious anemia
folic acid deficiency
- most common cause of macrocytic anemia
alcoholism
- secondary to malnutrition
chronic liver disease
What causes microcytic anemia
iron deficiency anemia, thalassemia, lead poisoning, and anemia of chronic illness/disease
What does MCH mean
mean corpuscular Hg
measures average amount of hemoglobin within an RBC
What increases and decreases MCH
increases: macrocytic anemias
- MCH increases as size of RBC increases
decreases: microcytic anemias and hypochromic anemias
- MCH decreases as size of RBC decreases
What does MCHC mean
measure of the average concentration or percentage of hemoglobin within a single RBC
Decreased MCHC means
deficiency of hemoglobin
- hypochromic
What increases and decreases MCHC
increases: spherocytosis, IV hemolysis, cold agglutinins
decreases: iron deficiency anemia, thalassemia
What is RDW
red blood cell distribution width
- indicates variation in RBC size
measured using MCV and RBC values
indicates a degree of anisocytosis
- blood condition characterized by RBC’s of variable and abnormal size
What can increase RDW
iron deficiency ANEMIA
hemoglobinopathies
- sickle cell
