Physiology Exam 2

toripotent

can form all cell types including extramebryonic tissues

pluripotent

can become almost any cell type in body

multipotent

limited to differentiating into related family of cells

cell lineage

specific path a stem cell follows to become a specialized cell, determining its role in body

what can disruptions in differentiation lead to

developmental issues or cancers

transcription

DNA transcribed into messenger RNA

translation

mRNA translated into protein at ribosome

central role of proteins

• structural support

• catalysts

• communication (receptors, hormones)

• transport

• regulation

G1 phase (gap 1)

cell growth and preparation for DNA replication

S phase (synthesis)

DNA replication, resulting in two sets of chromosomes

G2 phase (gap 2)

further cell growth and preparation for mitosis

M phase (mitosis)

division of cell’s nucleus followed by cytokinesis (division of cytoplasm)

G1 checkpoint

ensures cell is ready for DNA synthesis

G2 checkpoint

checks for DNA damage before entering mitosis

M checkpoint

ensures proper chromosome alignment before cell division

what do mutations in cell cycle checkpoints cause

unchecked cell division, driving cancer

cancerous treatments

• chemotherapy: M phase target - drugs like Taxol prevent cells from dividing properly by disrupting mitosis

• targeted therapy: G1 phase inhibition - CDK inhibitiors block cell cycle progression, slowing tumor growth

mitosis

division of somatic cell into two identical daughter cells

• essential for growth, development, tissue repair

meiosis

• production of gametes with half genetic material of parent cell

• contributes to genetic diversity through recombination and independent assortment

karyotype

complete set of chromosomes in cell displayed in pairs

• used to identify chromosomal abnormalities such as Down syndrome

uncontrolled mitosis

formation of tumors, understanding mitosis crucial for developing treatments that target rapidly dividing cancer cells

meiosis danger

errors in meiosis can result in adnormal chromosome numbers, leading to conditions like Down syndrome and Turner syndrome

• can also impact fertility and cause infertility or miscarriages

DNA structure and function

• double helix

• nucleotides (sugar, phosphase group, nitrogenous base - ATCG)

• A with T, G with C

differences between RNA and DNA

RNA single-stranded, DNA double-stranded

types of RNA

• mRNA - carries genetic in from DNA to ribosomes

• tRNA - brings amino acids to ribosome

• rRNA - component of ribosome itself

chromosomal structure

• 46 chromosomes and 23 pairs

• genes distributed across chromosomes

mutations

change in DNA sequence that can impact gene function

• can lead to genetic disorders or contribute to development of diseases like cancer

process of maintaining stability within DNA

DNA repair processes work to correct errors, reducing harmful mutations and protecting genetic information

are occasional mutations good within genetics

yes they can occur naturally and introducing genetic diversity that can drive evolution

process of transcription

initiation → elongation → termination → processing

1. transcription factors and RNA polymerase attach to promoter region of DNA

2. RNA polymerase begins copying DNA at transcription initiation site until stop signal

3. DNA unwinds and RNA polymerase reads one strand of DNA to make matching mRNA strand

4. mRNA uses Uracil instead of Thymine

5. mRNA later used to make proteins

promoter region

RNA polymerase binds here and initates transcription

exon

DNA sequences that are transcribed into mRNA and translated into amino acid sequence of protein

intron

DNA sequences that are transcribed, but are spliced out of pre-RNA and not included in mRNA

terminator region

DNA sequence that signals end of transcription

what are the mechanisms of gene expression and regulation

genet expression is regulated in promoters, enhancers, and epigenetic modification

• promoters - DNA sequences where RNA polymerase binds to initiate transcription

• enchancers - DNA sequences that enhance rate of transcription

• epigenetic modifications - chemical changes to DNA or histones that affect gene expression without altering DNA sequences itself (ex. methylation)

phenotypic diversity

gene expression creates variation in traits, even with same genetic code

epigenetics

environment factors can turn genes on or off, influencing traits without changing DNA

tissue specialization

different genes are active in different tissues, allowing diverse cell functions

adaptability

dynamic gene regulation helps organisms respond to changes and adapt to their environment

environmental influence on genes

diet, stress, and toxins can alter gene activity, showing that gene expression changes with external conditions

methylation of DNA

methylation can turn genes on or off without changing DNA, and these changes can be long-lasting or even inherited

examples of autosomal dominant

Huntington’s disease (neurodegenerative disorder that affects movement, cognition, psychiatric health), Marfan syndrome

examples of autosomal recessive

Cystic fibrosis (affecting lungs and digestive system), sickle cell anemia (abnormal hemoglobin, leading to distorted red blood cells)

X-linked inheritance examples

Hemophilia, Duchenne muscular dystrophy

where do germ cells recombine

in zygote

pedigree analysis

tool used to trace inheritance of traits and genetic disorders through family generations

are most diseases mendelian or non mendelian

non-mendelian

examples of complex inheritance disease

type 1 diabetes, hypertension, heart disease, alzheimer’s disease, asthma

neoplasm

abnormal mass of tissue resulting from excessive cell division (benign or malignant)

benign tumor

generally localized, does not invade nearby tissues, slower growth rate

malignant tumor

invade surrounding tissues, may metastasize, more rapid growth rate

benign vs malignat tumors

benign

• cells closely resemble tissue of origin

• often encapsulated and growing in organized manner

• limited to site of origin

malignat

• cells may be poorly differentiated, exhibiting abnormal structures and functions

• irregular, invasive growth that disrupts normal tissue architecture

• capable of invading surrounding tissues and organs

cellular differentiation in tumors

extent to which tumor cells resemble normal cells of tissue from which they originate

well-differentiated tumor/benign

• ex. adenoma - benign tumor of glandular tissue that closely resembles normal glandular structure

• nomenclature - ends in -'oma and indicates benign nature

poorly differentiated tumor/malignant

• ex. anaplastic carnimona - malignant tumor where cells lose specialized features and no longer resemble tissue of origin

  • nomenclature - often in terms like carcinoma (epithelial origin) or sarcoma (connective tissue origin), indicating malignant origin

tumor progression

• tumors may begin as benign but can acquire genetic mutations that lead to malignant transformation

metastasis

process by which cancer cells spready from primary tumor to distant sites in body forming secondary tumor

angiogenesis

formation of new blood vessels provides nutrients and oxygen to tumors; tumors can secrete factors that stimulate angiogenesis

oncogenes

genes that have potential to cause cancer

activation of oncogenes

mutations or overexpression can convert proto-oconogenes (normal versions) into oncogenes, leading to uncontrolled cell proliferation

examples of oncogenes

• RAS - involved in cell signaling pathways; mutations can lead to continuous cell division

• MYC - transcription factor that regulates genes involved in cell growth, overexpression can lead to cancer

examples of proto-oncogenes

• growth factors

• growth factor receptors

• G proteins

• enzymes that produce second messengers

• genes that turn the production of these proteins on and off

what do oncogenes produce

• still code proteins needed for cell divison but could produce:

  • too much of a protein

  • abnormal protein

  • protein that turns on by itself

  • protein that is made when not needed

  • protein that cannot turn cell division off

  • protein that should be made by different cell

tumor progression

• gradual throughout a series of stages

• driven by accumulation of geentic mutations that provide tumor cells with growth advantage

tumor suppressor genes

genes that normally prevent uncontrolled cell growth but can proliferate uncontrollably when inactivated or lost

• examples: TP53/p53 and BRCA1/2

TP53/p53

“guardian of genome,” induces cell cycle arrest or apoptosis in response to DNA damage

BRCA 1/2

involved in DNA repair, mutations linked to increased risk of breast and ovarian cancer

epigenetic alterations

heritable changes that do NOT involve changes in underlying DNA sequences

• ex. methylation, histone

methylation

addition of methyl groups to DNA, often leading to gene silencing

histone modification

changes to histone proteins that affect chromatin structure and gene accessibility

driver mutations

mutations that directly contribute to cancer initiation and progression

passenger mutations

mutations that do not contirbute to cancer but are present due to genomic stability of cancer cells

multiple hit hypothesis

tumorigenesis typically requires multiple genetic alterations to key genes that control cell growth and division

example of “hits”

• oncogene activation - mutation that activates an oncogene, such as RAS, can lead to uncontrolled cell proliferation

• tumor suppressor gene inactivation - loss of function in tumor suppressor genes, such as TP53, removes cell’s ability to halt abnormal growth

• DNA repair defects - mutations in DNA repair genes like BRCA1, increase likelihood of accumulating additional mutations

pathways of metastasis spread

• vascular - cancer cells enter bloodstream and travel to distant organs

• lymphatic spread - cancer cells spread through lymphatic system, often leading to metastases in lymph nodes

• direct invasion - tumor invade neighboring tissues by penetrating surrounding structures

immune system interaction response to neoplasia

• immune serveillance - immune system detects and destroys abnormal cells, including cancer cells

• tumor immune invasion - cancer cells can evade immune detection by expressing immune checkpoint proteins or altering antigenic profile

tymor-associated antigens

proteins of molecules expressed on surface of cancer cells that can be recognized by immune system

• targeting tumor-associated antigens can enhcance immune system’s ability to fight cancer

what are the mechanisms of tumor spread

angiogenesis, epithelial-mesenchymal transition (EMT), extrasation

epihtetlial-mesenchymal transition (EMT)

proces where epithelial cells gain migratory and invasive properties, aiding in metastasis

extravasation

process by which cancer cells exit bloodstream or lymphatic system to establish new tumor in distant tissues

what are the common metastatic sites for tumors

• lung - bone, brain

• colon - liver

• breast - bone, brain, liver, lung

• prostate - vertebrae

• melanoma - brain

carcinogen

substances or exposures that can lead to cancer by causing genetic damage

• chemical, physical, biological

chemical carcinogens

tabacco smoke-lung cancer, asbestos, certain industrial chemicals

physical chemicals

ultraviolet radiation-skin cancer, ionizing radiation

biological carcinogens

certain viruses (ex. human papillomavirus-cervical cancer, hep B and C, H. pylori-stomach cancer)

hereditary cancer

cancers caused by inherited genetic mutations that are passed from parent to child

• ex. breast cancer - BRCA1/2 mutations, Lynch syndrome-colorectal cancer

sporadic cancer

cancers that occur due to mutations acquired over a person’s lifetime, not inherited

• influenced by lifestyle, environmental factors, chance

paraneoplastic syndrome

rare disorder triggered by immune response to a cancerous tumor

• endocrine - production of hormones by tumor, ex. Cushing’s

• neurological - disorders like Lambert-Eaton syndrom, where immune system attack nerve cells

• hematologic - conditions like anemia or thrombosis associated with certain cancers

what is the significance of paraneoplastic syndromes

can be the first sign of an underlying malignancy and may complicate cancer treatment

Cushing’s syndrome

• associated with small cell lung cancer

• tumor secretes ACTH→excessive cortisol production

Lambert-Eaton Myasthenic syndrome

• associated wiht small cell lung cancer

• immune response against tumor cells affects nerve function, leading to muscle weakness

trousseau’s syndrome (migratory thrombophlebitis)

• associated with pancreatic or gastrointestinal cancers

• tumor secretes procoagulant factors, leading to abnormal blood clotting

tumor staging

tumor staging is use to determine extent of cancer within body, which is critical for prognosis and treatment planning

tumor staging steps

0. Cancer in situ, localized and not spread

1. early stage, small tumor, no spread to lymph nodes or distant stages

2. and 3. larger tumors and/or spread to nearby lymph nodes

4. advanced stage, cancer has spread to distant organs (metastasis)

Tumor (T)

• T1-T4: describes size and extent of primary tumor

• T0: no evidence of primary tumor

• Tx: tumor cannot be assessed

Nodes (N)

• N0: no regional lymph node involvement

• N1-N3: describes extent and number of lymph nodes involved

Metastasis (M)

• M0: no distant metastasis

• M1: presence of distant mestasis

• Mx: distant metastasis cannot be assessed

cytogenetics

study of chromosomes and their structure, function, and behavior in relation to genetic diseases

• FISH, CGH, karyotyping

FISH (Fluorescence In Situ Hybridization)

detects specific DNA sequences on chromosomes, useful for identifying chromosomal abnormalities