Foundations Flashcards
Fetal placental structure that secretes hCG
syncitiotrophoblast
Maternal component of the placenta
Decidua basalis
Energy available to fuel endergonic reactions (anabolic)
glucose > pyruvate > Adenosine triphosphate > Adenosine monophosphate > Adenosine.
Stages of an embryo between conception and an inner cell mass
Zygote -> Morula -> Blastocyst -> Inner Cell Mass + Trophoblast
Deficiency of this gene causes holoprosencephaly
Sonic hedgehog gene - Produced at base of limbs in zone of polarizing activity
Lack of this gene results in short limbs
FGF gene - fibroblast growth factor: produced at apical ectodermal ridge, stimulates mitosis of underlying mesoderm - lengthens limbs
Homeobox (HOX) Genes
- BIueprt for skeletal morphology
- Code for transcription regulators
- Mutation in Homeobox HOXD-l3 synpolydactyly (extra fused digit between 3rd and 4th fuigers)
- Retinoic acid alters HOX gene expression
Surface ectoderm
- Adenohypophysis (from Rathke’s pouch) - Craniopharyngioma - benign Rathke’s puch tumor with cholesterol crystals, calcifications - it didn’t become induced by the notocord
- lens of eye
- epithelial linings of oral cavity, sensory
- organs of ear, and olfactory epithelium
- epidermis
- anal canal below the pectinate line
- salivary, sweat, and mammary glands
Neuroectoderm
- CNS and Brain
- Brain (neurohypophysis, CNS neurons,
oligod en drocy tes, astrocytes, ependymal cells,pineal gland) - retina
- spinal cord
Neural Crest
PNS and non-neural structures nearby (STAMPEDE to heart) “missionaries” of the neuroectoderm
Endoderm
- Gut tube epit helium (including anal canal above the pectinate line) and derivatives
- lungs
- liver
- pancreas
- thy mus
- parathyroid
- thyroid follicular cells
Mesoderm
- Muscle
- bone
- connective tissue
- seroas
- linings of body cavities (e.g., peritoneum),
- spleen (derived from foregut mesentery)
- cardiovascular structures
- lymphatics
- blood
- bladder
- urethra
- vagina
- eustachian tube,
- kidneys
- adrenal cortex
- skin dermis
- testes, ovaries
Mesodermal defects
Mesodermal defects = VACTERL
- Vertebral defects
- Anal atresia
- Cardiac defects
- **Tracheo - **Esophageal fistula
- Renal defects
- Limb defects (bone and muscle)
1 cause of mental retardation in the US
Fetal alcohol syndrome - Even just 1 drink a day can have deleterious effects. NO ALCOHOL WHATSOEVER! Cleft lip, cleft palate.
Relationship between notochord, neural plate, neural tube, and neural crest
- Notochord forms the neural plate.
- Neural plate - gives rise to the he neural tube and neural crest cells
Drugs contraindicated in pregnancy
- Antiseizures: Carbamazepine, Phenytoin, Valproate.
- Antibiotics: Aminoglycosides, Tetracyclines, Fluoroquinolones (cartilage abnormalities), Sulfonamides, Clarithromycin, Chloramphenicol (gray baby).
- Folate Antagonists: Pyrimethamine, methotrexate (kills ectopic pregnancies).
- Miscellaneous: ACE inhibitors, Thalidomide, Diethylstilbestrol (DES) Warfarin (Coumadin)
NCC derivative deficiencies
- Aganglionic colon,
- Albinism (melanocytes),
- Dental abnormalities(odontoblasts),
- PNS abnormalities,
- Abnormalities of bones and skull.
- Thyroid abnormalities from parafollicular (C) cells,
- Adrenal abnormalities from chromaffin cells,
- Disruptions of the aorticopulmonary septum.
Nuclear Lamins
provide the structural framework for DNA and the nuclear envelope
Are responsible for fostering the progression through the cell cycle.
Cyclins and Cyclin-Dependent Kinases
Cyclin-CDK complexes that assist in the progression from G1 phase to S phase
Cyclin D + CDK4 and Cyclin E + CDK2. “D-K4 and E-K2”
“Good 1 Sporting: Dave cycles up K4, Eric cycles up K2”
Cyclins-CDK complexes that assist in the progression of G2 to M phase
Cyclin A + CDK2 and Cyclin B + CDK1
“Good SECOND Mountain (to climb) Alex cycles up K2, Bob cycles K1”
In I-cell disease, there is a deficiency of
- Mannose Phosphorylation - no mannose-6-phosphate to target lysosomal proteins -> secretion out of cell instead of into lysosomes
- Mannose-6-Phosphate is a molecule that targets proteins in the endoplasmic reticulum for lysosomes
- Death by age 8
- (+) corneal clouding, course facies, HSM, skeletal abnormalities, restricted joint movement, +/- MR
Nuclear localization signals contain these amino acids.
Lysine, Arginine, Proline
Granulomatous diseases
- Mycobacterium tuberculosis
- Fungal infections (e.g., histoplasmosis)
- Treponema pallidum (syphilis)
- M. leprae (leprosy)
- Bartonella henselae (cat scratch disease)
- Sarcoidosis
- Crohn’s disease
- Berylliosis
- Listeria
- Foreign bodies
- Wegner’s
- Chronic granulomatous disease
Leukocyte extravasation
- Rolling (selectins)
- Tight binding (integrins)
- Diapedesis (PECAM-1
- Migration (CILK)
C-Reactive Protein
- Acute-phase reactant synthesized by the liver
- Part of the innate immune response: opsonizes bacteria and activates complement clears microbes
- Can be secreted from cells within atherosclerotic plaques to activate local endothelial cells to induce a prothrombotic state and increase the adhesiveness of the endothelium to leukocytes
- Elevations are a strong predictor of Ml, stroke, PAD, and sudden cardiac death
- CRP can be lowered by smoking cessation, exercise, weight loss, and statins
Elevated ESR
- Polymyalgia rheumatica
- Temporal arteritis
- Disease activity in RA and SLE
- Infection, Inflammation (osteomyeliis)
- Malignancy
**Epithelial Wound Healing **
- 0-3 hours - Hemorrhage and clotting
- 12-24 hours - Acute inflammation (PMN)
- 2-4 days - Macrophage infiltration and epithelial cell migration
- 3-5 days - Granulation tissue (especially at wound edges)
- Months - Collagen production (type Ill then type I)
Findings associated with Ehlers-Danlos syndrome
- Hyperextensible skin,
- tendency to bleed (easy bruising),
- Hypermobile joints.
- Aneurysms.
- Type III collagen most frequently affected.
Types of collagen
- Type I: Tendon, bone, dentin, skin, fascia, cornea;
- Type II: Cartilage, vitreous body;
- Type III: Blood vessels, granulation tissue, uterus, fetal tissue;
- Type IV: Basement membrane.
Amino acids found in large concentrations in collagen
- Glycine, Proline, hydroxyproline, hydroxylysine.
- Elastin: Rich in proline and glycine, nonglycosylated forms.
4 transcription factors essential in pluripotent stem cells
- Oct3/4
- myc-c
- SOX2
- KLf4
Amino Acids modified in the Golgi apparatus
Serine, Threonine, Asparagine
$$$ What structures are derived from the Endoderm?
Parenchyma of:
- Liver
- Thyroid
- Pancreas
- Parathyroids
Epithelial lining of:
- Respiratory tract
- tonsils
- thymus
- bladder, urethra
- tympanic cavity
- auditory tube
- GI tract
Fetal landmark within 1 week
hCG secretion begins after implantation of blastocyst
Fetal landmarks within week 2
How does the primitive streak form? What does the primitive streak give rise to?
- 2 germ layers Bilaminar disk (epiblast, hypoblast)
- 2 cavities: amniotic cavity, yolk sac
- 2 components to placenta: cytotrophoblast, syncytiotrophoblast
Epiblast (precursor to embryo) invaginates to form the primitive streak. Cells from the primitive streak give rise to both
- **intraembryonic mesoderm **
- endoderm (part of)
Fetal landmarks within week 3
- 3 germ layers (gastrula)Trilaminar disc
- Gastrulation
- Primitive streak, notochord, mesoderm and its organization
- Neural plate begins to form
Fetal landmarks weeks 3-8
(embryonic period)
- Neural tube formed by neuroectoderm and closes by week 4
- Organogenesis
- Extremely susceptible to teratgens
Fetal landmarks Week 4
- Heart begins to beat
- Upper and lower limb buds begin to form
Fetal landmarks week 8
(Fetal period)
- MOVEMENT!
- Fetus looks like baby
Fetal landmarks
Week 10
Genitalia have male/female characteristics
When Rb protein comes unbound from this transcription factor, the cell can prepare to move from G-1 into S phase.
Transcription factor E2F
- Cyclin D binds/activates CDK4 ->
- Phosphorylation of RB protein ->
- RB protein is released from transription factor E2F ->
- with E2F unbound, the cell is free to transcribe/synthesize components needed for progression through the S phase (cyclin E, DNA polymerase, thymidine kinase, dihydrofolate reductase)
When do endosomes become lysosomes?
Endosomes become lysosomes when hydrolytic enzymes enter.
Organelle of critical importance for Neural tissue
Peroxisomes and Plasmalogens
Involved in the catabolism of very long chain fatty acids and amino acids
What is a proteasome?
What are 3 ways proteins can be degraded?
- Barrel-shaped protein complex
- Degrades damaged or unnecessary proteins tagged for destruction with ubiquitin
3 ways to degrade protein:
- Ubiquitin mechanism
- Lysosome degradation
- Calcium dependent enzyme - not in lysosome
Rb protein and p53 regulate the cell cycle by
Preventing the Cell from Progressing From G1 Phase -> S Phase
Staining of the following intermediate filament is useful to ID which cell type?
Vimentin
- Connective tissue
- Sarcomas
- Some carcinomas
Staining of the following intermediate filament is useful to ID which cell type?
Desmin
- muscle
- myosarcoma
Staining of the following intermediate filament is useful to ID which cell type?
Cytokeratin
- Epithelial cells
- IDs Carcinomas
- some sarcomas
Staining of the following intermediate filament is useful to ID which cell type?
GFAP
- NeuroGlia
- Astocytomas
- GBM
Staining of the following intermediate filament is useful to ID which cell type?
Neurofilaments
- Axons within Neurons
- Adrenal neuroblastoma
- Primitive neuroectodermal tumors (PNETs)
Note: Neurons can be IDed via peripherin
Staining of the following intermediate filament is useful to ID which cell type?
Nuclear lamins (A,B,C)
Mutations in nuclar lamins result in what disease?
Nuclear envelope and DNA within
Example: Cyclin B and CDK1
Progeria - advanced cellular aging ( 5yo looks like an old man)
Apoptosis cannot be initiated in the presence of severe DNA damage if this protein is mutated?
p53 - triggers apoptosis if DNA damage is present and the DNA repair process fails
Bax
Pro-aptotic
Bcl-2
Anti-apoptotic, if levels are reduced, intrinsic pathway of apoptosis occurs
CD31
Prevents apoptosis (expressed on surface of healthy cells)
Histologic features of apoptotic liver cells
- Cell shrinkage
- Pyknosis (basophilia)
- Nuclear fragmentation(karyorrhexis)
- Nuclear fading (karyolysis)
- Membrane blebbing
- Formation of apoptotic bodies
Substances that can trigger apoptosis
- Deprivation of growth factors,
- Cell stress,
- DNA is damaged and repair fails,
- Cytokines (TNF) triggers apoptosis,
- Cytotoxic T cells insert granzyme B
Cellular particles responsible for handling oxygen free radicals are
- catalase
- Superoxide dismutase
- Glutathion peroxidase
What byproducts might e detected in the serum when the following cell type is injured:
Cardiac myocytes
- CK
- LDH
- troponin
What byproducts might e detected in the serum when the following cell type is injured:
Skeletal myocytes
- CK
- Aldolase
- LDH
What byproducts might e detected in the serum when the following cell type is injured:
Hepatocytes
- AST
- ALT
- Alkaline phosphatase
- GGT
What byproducts might e detected in the serum when the following cell type is injured:
Salivary gland cells
- Amylase
What byproducts might e detected in the serum when the following cell type is injured:
Pancreatic exocrine cells
- Amylase
- Lipase (more specific)
What byproducts might e detected in the serum when the following cell type is injured:
RBCs
- LDH
- Haptoglobin
- bilirubin
Leukocyte adhesion deficiency syndrome
abnormal LFA-1: Delayed separation of the umbilicus, recurrent bacterial infections
Elevated ESR is especially seen in these diseases
- Polymyalgia rheumatica
- Temporal arteritis
- Diseases activity in RA and SLE
- Infection, Inflammation (osteomyelitis)
- Malignancy
Reduced in
- SCA
- PCV
- CHF
Where can tissue stem cells be found in the Brain?
Neural precursor cells in the subventricular zone and dentate gyrus of the hippocampus
