All CTT Flashcards by Meghan Hewlett

What are the two regions of the platelet?

The granulomere and the hyalomere

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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,

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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.

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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

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What types of granules do all granulocytes have?

primary granules: lysosomes

secondary/cell-specific granules

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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

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What is the internum

It is the dense core of an eosinophilic granule - it contains major basic protein

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What is an externum

It is the surrounding part of an eosinophilic granule

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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.)

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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

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responsible for vascular disturbances, such as widespread vasodilation, associated with hypersensitivity and anaphylaxis.

basophil

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What is the order of layers in an uncoagulated centrifuged tube of blood?

Top: plasma, platelets, WBCs, RBCs

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When fresh blood coagulates, what is the order of layers?

blood serum, blood clot

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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.

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What is the buffy coat?

WBCs, constitutes 1% of total volume

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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.

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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

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RBC lysis within the phagocytes

extravascular hemolysis

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Antibodies in a Type A or B mother

IgM (not taken up by placenta)

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Antibodies in a type O mother

IgG (taken up by placenta)

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Assessment of Extrinsic Pathway

average time?

Prothrombin time

10-14s

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Assessment of Intrinsic Pathway

average time?

Partial thromboplastin time

30-50 secs

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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

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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.

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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