All CTT Flashcards
What are the two regions of the platelet?
The granulomere and the hyalomere
What is the granulomere?
Platelet: the central region, containing mitochondria, glycogen, and three types of cytoplasmic granules functionally related to its role in blood clotting,
What is the hyalomere
Platelet: the clear peripheral region, which contains an encircling ring-shaped marginal band of microtubules that serve to maintain the lens-shape of the platelet. The high concentration of actin and myosin in the hyalomere play a role in the retraction of the platelet after the clot has served its function. Two tubular systems, a dense tubule and a surface-opening set of tubules assist in the delivery of the contents of the granules to the exterior.
What are the granules in the platelet? Where are they located?
Alpha granules: fibrinogen, pdgf, coagulation factors,
lambda granules: lysosomes (hydrolytic enzymes)
delta granules: dense bodies - adp, atp, ca2+, serotonin
What types of granules do all granulocytes have?
primary granules: lysosomes
secondary/cell-specific granules
What granules do neutrophils have?
What else do they secrete? what is it?
primary granules: lysosomes
secondary/cell-specific granules: kill bacteria with enzymes and reactive oxygen compounds (antimicrobial)
tertiary: facilitate migration to target
IL-1; a pyrogen
What is the internum
It is the dense core of an eosinophilic granule - it contains major basic protein
What is an externum
It is the surrounding part of an eosinophilic granule
exists with IgE antibodies bound to its surface
basophil (mast also has these in CT, they bind to mast and cause Ca2+ signal for degranulation.)
What do basophil granules contain? (cell specific)
The granules contain pharmacologically active agents such as histamine and heparin, as well as eosinophil chemotaxic factor and neutrophil chemotaxic factors
responsible for vascular disturbances, such as widespread vasodilation, associated with hypersensitivity and anaphylaxis.
basophil
What is the order of layers in an uncoagulated centrifuged tube of blood?
Top: plasma, platelets, WBCs, RBCs
When fresh blood coagulates, what is the order of layers?
blood serum, blood clot
In coagulated blood, the clot of blood consists of:
blood cells in a tangle of fibers, and includes large proteins as well as all the coagulation proteins that are normally present in blood plasma.
What is the buffy coat?
WBCs, constitutes 1% of total volume
Besides water, what else is in plasma? What percentage total is this other stuff?
9% proteins, which include albumen, globulins, clotting proteins (fibrinogen and prothrombin), electrolytes, glucose, and other molecules that are in balance with the tissue fluid.
Usually occurs as a result of transfusion reactions or Rh-incompatability. cells may also lyse in the circ in response to some toxins
intravascular hemolysis
RBC lysis within the phagocytes
extravascular hemolysis
Antibodies in a Type A or B mother
IgM (not taken up by placenta)
Antibodies in a type O mother
IgG (taken up by placenta)
Assessment of Extrinsic Pathway
average time?
Prothrombin time
10-14s
Assessment of Intrinsic Pathway
average time?
Partial thromboplastin time
30-50 secs
Prothrombin time measures the integrity of ____________ It is independent of defects in factors, _______ or
_____.
the extrinsic systems, factors VII, X, II,
V and I (fibrinogen).
XII, XI, VIII, or platelets
Partial thromboplastin time measures the integrity of factors ____________ It is unaffected by defects in factors, _______ or
_____.
XII, XI, IX, VIII, X, V, II and I but is unaffected
by defects in VII or platelets.
When caretaker genes are inactivated, what occurs re: mutations?
the rate at
which additional mutations accumulate is accelerated
Caretaker genes are genes involved in:
DNA repair
inactivation of _______ genes is often an early event that creates genome
instability, and subsequently promotes carcinogenesis
Caretaker or tumor suppressor?
caretaker
How can gain-of-function mutations lead to the dysregulation of oncogenic activity (cell cycle dysregulation and possibility of oncogenesis)?
interfere with proper regulation
of proto-oncogenic activities or that amplify the number of copies of protooncogenes
What kinds of proteins are encoded by oncogenes (proto-oncogenes)? (4)
How are they different? How are they the same?
growth factors,
growth factor receptors, signal transduction molecules, and nuclear transcription
factors
involved in different aspects of the
cell growth cycle and have different modes of oncogenesis.
disruption of any of these components yields essentially the same result:
disregulation of the cell cycle and the possibility of oncogenesis
miRNA molecules that are
responsible for the post-transcriptional regulation of upwards of 200 unique
genetic targets per miRNA gene
Give one example of how they can act as oncogenes
onco-miRs
by inhibiting large numbers of tumor suppressor genes
most oncogene-based tumors are ______ in
nature and often result from acquired mutations in oncogenes such as: (3)
sporadic;
ras, myc, src
At the cellular level, oncogenes act in a ______ fashion.
Tumor suppressor genes at the cellular level act in a _______ fashion
dominant; recessive
What are the four chromosome instability syndromes?
What types of mutations are these?
Xeroderma pigmentosum,
ataxia telangiectasia, Fanconi anemia, and Bloom syndrome.
homozygous recessive
patients harbor a mutation in a gene required for
nucleotide excision repair
Sensitive to what type of radiation?
Xeroderma pigmentosum; UV
Note: UV is also ionizing radiation
patients are hypersensitive to ionizing radiation
because the ATM mutation prevents proper DNA damage repair for double stranded
breaks.
Why is this bad?
Ataxia telangiectasia; The presence of DNA free ends generates a highly unstable
genomic state, and these fusogenic ends often associate inappropriately to create
new translocations.
first manifests as loss of balance and slurred
speech during the toddler years. The patients experience continued cerebellar
degeneration, radiosensitivity, immunodeficiency, sterility, and predisposition to
developing tumors, particularly lymphomas.
characteristic karyotype
Ataxia telangiectasia
patients harbor genetic lesions in proteins that interact
with ATM, and as such, they are also acutely sensitive to agents that cause
double-stranded breaks, such as ionizing radiation
Fanconi anemia
These patients typically
experience bone marrow failure as their primary symptom, along with skeletal
abnormalities, thumb malformations, abnormal pigmentation and increased risk of malignancy.
what’s seen in the karyotype?
Fanconi anemia; triads
patients have mutations in yet another protein complex that interacts with the
ATM and Fanconi proteins.
Therefore, they are also acutely sensitive to ionizing
radiation and demonstrate severe growth deficiency, early menopause in women, infertility in men, and
recurrent infections and wide cancer susceptibilities.
What’s seen in the karyotype?
Bloom syndrome; excessive crossing over
Another tumor suppressor that is inactivated in about 50% of human
cancers is p53, and inheritance of a mutated copy of this gene is the cause of:
These pts. are predisposed to a large variety of cancers
Li-Fraumeni syndrome
Although tumor suppressor genes themselves harbor recessive loss-offunction
mutations, they appear to be inherited in a dominant fashion in:
families and pedigrees
The phenotype of patients heterozygous for tumor suppressor mutation is described as:
incompletely penetrant
genes show some involvement in DNA repair
processes, particularly in the ATM pathway
BRCA1 and BRCA2
are also associated with 10-20%
of all cases of male breast cancer
BRCA2
In tumors homozygous for either BRCA1 or BRCA2 mutations,
chromosomes are:
What does this suggest?
rearranged; suggests that they normally play a role in
preserving chromosome structure
Most of these BRCA mutations lead to a loss-of-function resulting from _____ and_______________ of the
BRCA proteins.
frameshifts and premature truncation
With expression profiling, ____________ are isolated and labeled from the patient samples.
RNA molecules
In Dr. Robert Weinberg’s progression model, all
tumors must acquire a common set of six properties which are:
self-sufficiency
in growth signals (oncogene activation),
insensitivity to anti-growth signals (loss
of tumor suppressor function),
evasion of apoptosis,
limitless replicative
potential (e.g. from telomerase reactivation),
sustained angiogenesis
(recruitment of blood supply to the tumor),
and tissue invasion and metastasis.
What are examples of the six required capabilities needed for all tumors:
self-sufficiency
in growth signals:
insensitivity to anti-growth signals
evasion of apoptosis,
limitless replicative
potential
sustained angiogenesis
and tissue invasion and metastasis.
self-sufficiency
in growth signals: Active H-Ras oncogene
insensitivity to anti-growth signals: Lose Rb suppressor
evasion of apoptosis: Produce IGF survival factors
limitless replicative
potential : turn on telomerase
sustained angiogenesis: Produce VEGF inducer
and tissue invasion and metastasis: Inactive E-cadherin
Distinguish between the hallmarks of familial cancers and sporadic cancers
mendelian/familial (arising from inherited germline and then somatic mutation): multiple tumors, bilateral, early-onset
sporadic (two somatic mutations): single tumors, unilateral, later onset
P53’s involvement in multiple pathways leads to:
pleiotropy
Besides diagnostics, what are other clinical applications for microarray technology in oncology?
to Identify genes that have changed copy number as a cancer causing mutational event.
for at risk individuals, providing a genomic surveillance method to predict development (or to detect early development) of cancer
What are the CD numbers expressed on RBCs? Platelets?
CD235, CD41
Initiates inflammatory response in CT
Mast cell
What cells are part of the second wave of the cellular response (after neutrophils)?
Monocytes
Why is it difficult for tendons to heal?
They are poorly vascularized
Under what circumstances does a lymphocyte become another cell?
When it enters the CT AND is stimulated by antigenic material
generates all non-lymphoid lineages.
CMP
progenitor cell requires several cytokines for survival high proliferative potential 14 days to RBCs in culture motile – can be present in peripheral blood (!)
BFU-E
progenitor cell
highly dependent on EPO
7 days to RBCs in culture
non-motile, found in marrow only
CFU-E
What are the lineages of mast cells? where do they develop?
CMP > CFU-GM > CFU-M > Monocyte; periphery
How many nuclei does a megakaryocyte have?
one
What cells have an external lamina?
Schwann cells, muscle cells, and fat cells
What shapes does a transitional epithelium go between?
stratified cuboidal (relaxed) and stratified squamous (stretched)
The Z lines are anchored to the sarcolemma by _______, which link the internal cytoskeletal system of individual myofibers to the extracellular matrix.
Costameres
is found at both M lines and Z lines and helps to hold the myofibrils in vertical register.
Desmin
Believed to control the length of polymerized actin filaments
nebulin
spans the distance from the Z-line to the M-line of myosin, connecting the two.
titin
present at the M-line (as well as in the sarcoplasm) catalyzes the production of ADP and phosphocreatine from ATP and creatine during muscle contraction; the reaction is reversible and thus can also replenish the ATP store
Creatine kinase
assayed in blood tests as a marker for muscle breakdown
creatine kinase
What are two types of myofilaments?
actin and myosin
The endomysium is made up of delicate reticular fibers that surround each muscle fiber, just beyond the ______ of the muscle ____.(fiber or fibril)
external lamina; fiber
In the contracted sarcomere, what bands change and what do not?
I-band and H-band become narrower, and A band doesn’t change
How do Red and white sk. muscle fibers differ in EM?
PAS? (IA, IIA, IIB)
Cytochrome oxidase?
Red: more mitochondria, and wider z-lines.
PAS: IA - palest, IIB - pinkest because most glycolytic
Cytochrome oxidase: IA - intense dark brown; IIB - palest
Form dyads; where are they located?
form Triads; where are they located?
which muscle type has more mitochondria?
Cardiac muscle; z-lines
skeletal muscle; A-I interface
cardiac
What are the two types of cardiac muscle fibers?
myocardial endocrine cells and cardiac conducting cells
Many cardiac muscle cells located principally in the atrium of the heart are
myocardial endocrine cells
myocardial endocrine cells resemble working atrial myocytes except they contain membrane-bound secretory granules that contain the precursor of a peptide hormone called
ANP
In comparison to the standard myocytes, they are interconnected with a greater number of gap junctions, have a lower content of myofilaments, and a higher content of glycogen
cardiac conducting cells
Which is faster? intrinsic or extrinsic pathway?
Extrinsic
What aids antithrombin?
heparin
