10/2 Flashcards
Anatomical Position
Body is erect (upright), facing forward, feet together and parallel, feet flat in floor, head level with eyes facing forward, palms facing forward and thumbs point away from body
Body lying down-
Prone: face down
Supine: face up
Anatomical Directional Terminology
Anterior (Ventral): toward the front of the body (belly)
Posterior (Dorsal): toward the back of the body (butt)
Superior (Cranial): toward the head or upper part of a body/structure
Inferior (Caudal): away from the head or upper part of a body/structure
Proximal: closer to the origin of a body part, leg attached to trunk, arm attached to shoulder
Distal: further from the origin of a body part
Human Body Planes and Sections
Sagittal: creates right/left halves, midsagittal/median divides into equal halves, parasagittal divides into unequal parts
Frontal (Coronal): divides into anterior/posterior parts
Transverse (Horizontal): divides into superior/inferior parts
Anatomical Terminology for Movements
Gliding (Translation): simplest, flat surfaces glide or slip over one another, intercarpal and intertarsal joints
Flexion: decreases angle in a joint
Extension: increases the angle in a joint, hyperextension if move head past 180°
Abduction: moving a limb away from the median plane of the body, raise arm
Adduction: moving a limb towards the median plane
Circumduction: moving a limb so that it creates a cone in space, distal end of limb moves in a circle while proximal connection is basically stationary
Includes flexion, extension, adduction, abduction
Rotation: turning a bone around its own axis, can be medial or lateral
Plantar flexion: depress the foot, pointing of the toes
Dorsiflexion: brings the superior surface of the foot towards the shin
Inversion: sole of the foot turns medially
Eversion: soles faces laterally
Pronation: rotating the forearm medically, palm is posterior, radius is across the ulna
Supination: radius and ulna are parallel, palm is anterior, anatomical position
Protraction: nonangular anterior movement in transverse plane
Retraction: posterior movement in transverse plane
Opposition: saddle joint between metacarpal 1 (at thumb), touch thumb and another fingertip
Superficial Veins of the Upper Limb
Cephalic Vein: runs along lateral upper limb, drains into axillary vein
Basilic vein: runs along medial forearm, dives through brachial fascia and becomes axillary vein
Median Cubital Vein: communicating branch between cephalic Vein and basilic vein in cubital fossa, used for venipuncture
Dorsal Venous Network: veins of the hand
Major Arteries of the Upper Limb
Brachial artery
Radial artery
Ulnar artery
Superficial Veins of the Lower Limb
Great saphenous vein: courses anterior to medial malleolus, ascends up medial leg and thigh, drains into femoral vein
Small saphenous vein: courses posterior to lateral malleolus, as ends up the posterior leg, dives deep in popliteal fossa, drains into popliteal vein
Dorsal venous arch
Cutaneous Nerves of the Upper Limb
Intercostobrachial nerve
Medical cutaneous nerve of forearm
Lateral cutaneous nerve of forearm: cutaneous branch of musculocutaneous nerve
Radial nerve
Arteries of the Lower Limb
Femoral Artery
Popliteal Artery
Posterior Tibial Artery
Anterior Tibial Artery
Dorsalis Pedis Artery
Femoral Triangle
NAVL
Femoral Nerve
Femoral Artery
Femoral Vein
Lymph Nodes
Cutaneous Nerves of the Lower Limb
Anterior Cutaneous Branches of Femoral Nerve
Saphenous Nerve (from femoral nerve)
Superficial fibular nerve becoming dorsal digital nerves
Posterior cutaneous nerve of thigh
Medical sural cutaneous nerve (from tibial nerve)
Sural nerve
Pulse Points of the Upper Extremity
Axillary
Radial
Ulnar
Brachial
Pulse Points of the Lower Extremity
Femoral
Posterior tibial
Dorsal pedis
Popliteal
Nuclear Changes in Neoplastic Cells
High nucleus:cytoplasm ratio
Multiple nuclei, piling up of nuclei
Multiple and large nucleoli
Coarse chromatin, makes nucleus stain darker than normal cells
Pleomorphism
Irregular chromatin
Irregular nuclear membranes
Increased presence of mitotic figures
Abnormal mitotic figures: sign of aneulploidy and anaplasia, loss of cell polarity leads to alteration in the mitotic spindle or excess centrosomes
Cytoplasmic Features of Neoplastic Cells
Hypercellularity
Pleomorphism, Abnormal cell contours
Anaplasia: poor cellular differentiation, lose characteristics of mature cells, and orientation with respect to each other
Loss of cell polarity
Clinical Aspects of Hyperplasia
- Physiologic Hormone Stimulation-
Normal response to hormone: estrogen stimulates proliferation of endometrial epithelial cells that converts proliferative endometrium into secretory endometrium
Response to tissue loss: hyperplasia of liver tissue after surgery due to HGF and IL-6
- Pathologic Hormone Stimulation-
GF or cytokine stimulation
Excessive response to a hormone or excessive hormone production: excess estrogen causes hyperplasia of the TDLUs in the breast, increased dihydrotestosterone causes prostate nodular hyperplasia
Inflammation, abnormal wound healing: psoriasis causes epidermis hyperplasia
Progressive Endometrial Changes to Carcinoma
- Proliferative Endometrium: normal
- Simple Hyperplasia: increased number of glands that are more densely packed
- Complex Hyperplasia with atypia: increased number of glands with reduced intraglandular stroma, glands lined by Cells with Neoplastic changes changes like loss of polarity and nuclear piling up
- Adenocarcinoma: like previous but has invasion of myometrium
Metaplasia
Distal esophagus: stratified squamous becomes columnar intestinal goblet cells that secrete mucin to deal with gastric reflux
Airways: pseudostratified ciliated columnar becomes stratified squamous due to smoking
Cervix: glandular becomes stratified squamous due to low pH or HPV
Urinary bladder: urothelium becomes stratified squamous to deal with stones or parasites
Dysplasia
Disorderly cell growth and maturation that leads to architectural disorganization of the epithelium, doesn’t always lead to cancer
Mild to severe based on how much of the epithelium is replaced by abnormal cells
Carcinoma in situ has the cellular/nuclear features of neoplasia but no basement membrane penetration
Proto-oncogene vs. Oncogene
- Proto-oncogene: normal gene that can become an oncogene with a single GOF of a single allele
Regulate cell growth/differentiation, signal transduction, mitosis signals
- Oncogene: proto-oncogene with a GOF change
Activation method: GOF mutation, loss of regulation, increased mRNA stability and life expectancy in cell, increase in copy number
Proto-oncogene conversion
- Mutation in coding sequence: hyperactive protein made in normal amounts
- Gene amplification: normal protein greatly overproduced, usually a late change rather than driver, requires higher doses of treatment
Caused by unequal crossing over, replication slippage, aneuploidy
Childhood neuroblastoma: originate from any SNS tissue but mainly adrenal gland, amplification of MYCN that is a TF for neural crest cell proliferation/differentiation
Breast cancer: HER2/ERBB2, epidermal GF receptor, detected by tissue immunochemistry (3+) or FISH (>6 copies/nucleus), Trastuzumab (Herceptin) is a monoclonal antibody for the HER2 receptor
- Chromosome Rearrangement-
A: Nearby regulatory DNA sequence causes normal protein to be overproduced
B: Fusion to actively transcribed gene greatly over produces fusion protein, or fusion protein is hyperactive
Oncogene Activation by Chromosomal Translocstion
Somatic change, not inherited
Typical cause of lymphoma and leukemia
Chronic leukemia: normal differentiation but increased proliferation
Acute Leukemia: abnormalities in both differentiation and proliferation
Chronic Myeloid Leukemia
GOF activations of tyrosine kinases
BCR/ABL gene fusion
Translocation between chromosomes 9 and 22, Philly chromosome, 3 lengths so 3 leukemias
Treatment: Imatinib is a tyrosine kinase inhibitor, also use a small molecule called phenylaminopyrimidine
Blocks ATP access at kinase pocket, develop resistance so need second line of inhibitors
RET
Receptor tyrosine kinase for ligand of the glial cell line derived neurotrophic factor
Types of changes: germline GOF mutations, somatic fusion gene, LOF mutations
Constitutive autophosphorylation or change of substrate specificity in tyrosine kinase region, covalent intermolecular disulfide bonds in cysteine rich region
Multiple Endocrine Neoplasia Type 2
All caused by GOF mutations of RET
Cysteine-rich region: extracellular region, MEN2A/FMTC, hyperparathyroidism, tumor in adrenal gland, most common MEN2
First Tyrosine Kinase region: FMTC, tumor of calcitonin-producing C cells of thyroid, thyroidectomy at early age
Second Tyrosine Kinase Region: MEN2B/FMTC, earlier age of onset, developmental abnormalities like neuromas of the mouth and increased intestinal innervation
Carcinogenesis: The Basics
Mutations that allow tumor growth involve tumor suppressor genes, proto-oncogenes, and apoptosis regulators
Proto-oncogenes: GFs, GF receptors, and signal transducers like RAS
Knudsen Two-Hit Hypothesis: both alleles must be knocked out of tumor suppressor genes to have tumor formation
Bcl2: blocks release of cytochrome C from mitochondria and the ensuing apoptosis, tumors overexpress Bcl2 to prevent apoptosis, translocation makes Cell make Bcl2 instead of Ig heavy chain
Multi step Carcinogenesis
- Tumor Initiation: due to irreversible genetic damage or epigenetics, causes a genetic error in stem cells by modifying its DNA structure like with a chemical adduct
- Tumor Promotion: selective clinal expansion of initiated cells,nude to defects in cell growth or programmed cell death
Foster the proliferation or expansion of a pop. of initiated cells
- Malignant Conversion: transformation of a pre-Neoplastic cell into one that expresses the malignant phenotype and usually requires further genetic changes
Summation of effects of initiators and promoters and the downstream effects they induce
- Tumor progression: expression of malignant phenotype and tendency of malignant cells to acquire more aggressive characteristics over time to become capable of spreading
Requires genetic change
Cancer Initiators
Direct-acting compounds: don’t require chemical transformation, directly capable of reacting with DNA
Indirect-acting compounds: require metabolic conversion (often made electrophilic) to generate ultimate carcinogen, initiators are often tissue specific
Form DNA adducts that are covalently bound to nucleoside, not repaired and must be replicated
Effect is irreversible, permanent genetic changes that daughter cells carry
Linear relationship between initiator dose and quantity of tumors
Cancer Promoters
Don’t covalently bind to DNA/macromolecules, can bind to receptors on cell surface that leads to increased cell proliferation
Tumor growth has threshold and maximum effects
Mechanisms-
1. Epigenetic
- Promoters induce cell proliferation, not mutagenic, like activate PKC
- Cells responding to promoters may have reduced GF Requirements or be less responsive to Inhibitors
- Oxidative stress: ROS, redox active metals like As/Cr/Ni, and polycyclic aromatic compounds like Dioxin
Chemical Carcinogens
- Direct-alkylating agents: chemotherapeutic drugs, can cause secondary malignancy
- Polycyclic Hydrocarbons: cigarette smoke, broiled animal fat, smoked meat/fish
Need metabolism, why 15% smokers get lung cancer
Vinyl chloride exposure leads to hepatic angiosarcoma with dark red masses
- N-Nitrosamines: occur in smoke, water, alcohol, meats
Mainly cause gastric carcinomas in Japan
- Aromatic Amines and Azo Dyes: from rubber industry, need metabolism
Urothelial carcinoma
- Aflatoxin B1: from fungus Aspegeilus flavus, needs Metabolism, binds guanine residues in the TP53 gene and causes mutations
Hepatocellular carcinoma
Inflammation as a Carcinogen
Chronic inflammation like IBS can cause colorectal cancer
Initiation: ROS can damage DNA
Promotion: ROS, GFs, and cytokines released from inflammatory cells can foster proliferation of initiated cells
Progression: angiogenic factors, ECM synthesis and degradation
Radiation as a Carcinogen
- UV Radiation-
UVA: oxidation reactions that indirectly cause DNA damage, darkens and ages skin, penetrates deeper into epidermis so tans us
UVB: DNA photoadducts, sunburns, direct DNA damage from producing pyrimidine dimers
Initiator since cause DNA damage and mutations
Promoter by upregulating Inflammation that makes ROS and increased COX-2 activity
UVB Induced inflammation: dysregulation of apoptosis, mutations in p53, upregulation of COX-2 plays a role in squamous cell carcinoma
- Ionizing Radiation-
Creates free radicals, use radiation therapy
Breast, colon, thyroid, and lung cancer
Viral Carcinogens
- HPV: HPV Types 16 and 18 are found in most squamous carcinomas of the cervix
HPV viral oncoprotein E6 causes tags P53 for proteasome degradation, HPV viral oncoprotein E7 tags Rb for proteasome degradation
Squamous of vulva, vagina, anus, cervix, adenocarcinoma of cervix
- Epstein Barr Virus: Burkitt Lymphoma, infected B cells rearrange immunoglobulin genes to acquire t(8;14) that promotes cell proliferation by regulating c-Myc
Make c-Myc instead of immunoglobulin
Nasopharyngeal
- Hepatitis B Virus: Africa and Asia, liver injury and regenerative hyperplasia, Hbx protein binds to and inactivates p53 to interfere with growth suppression
- Human Herpes Virus 8 (HHV8): Kaposi’s sarcoma and certain lymphomas in HIV patients
Kaposi’s sarcoma: Neoplastic endothelial cells
- Human T-Lymphotropic Virus 1 (HTLV1): RNA virus, endemic in Japan and Caribbean, tropic for CD4 T Cells
Activates IL2 and IL2R resulting in polyclonal proliferation in which leukemia develops
