block 9- special systems Flashcards

Question

number of follicles across the lifespan

Answer 1

Follicles (in cortex): Primary → Secondary (fluid-filled) → Mature follicle (releases egg each month) - one ovum released each month - 400 in lifetime - birth ~2 million follicles -Puberty ~400,000 follicles -Atresia -> degeneration of primary follicles

Answer 2

In the female, two structures develop: Egg: Oocyte/ ovum + Supporting tissue:Follicle supporting cells: 1. granulosa cells (synthesis oestrogen, support follicle growth) 2. theca cells - develop only in secondary follicles are divided into: ○ Theca Interna - Androgen synthesis ○ Theca Externa – connective tissue

Answer 3

1. prenatal maturation - 5 million oocytes by month 4 prenatally → 2 million primary oocytes at birth Meiosis I begins but arrests in prophase I and remain like this until puberty 2. postnatal development (puberty -> menopause) - ~400,000 oocytes at puberty Monthly cycle: One completes meiosis I → Secondary oocyte (arrests at metaphase II) Meiosis II only completed if fertilization by sperm occurs

Answer 4

-from birth to puberty many primary oocytes degenerate (atresia) ○ Don’t know why! ○ 300,000-400,000 at puberty ○ Only ~400 will complete development & be ovulated

Answer 5

Primordial follicle = Primary oocyte + granulosa cells Primary follicle = one oocyte enlarges and granulosa cells divide at puberty Secondary follicle = fluid filled spcaes form in granulosa cells Tertiary (Mature) follicle: Enlarge and fluid-filled space forms single atrium -> ready to ovulate

Answer 6

* Oocyte completes 1st meiotic division = secondary oocyte * Secondary oocyte begins (but does not complete) 2nd meiotic division –is again suspended * This time, at metaphase; only completes division if fertilised by the sperm

Answer 7

= release of secondary ooctye and zona pellucida from the ovary into the peritoneal cavity - ooctye travels from fallopian tube to uterus - triggered by a surge in LH - lots of follicles mature each month but only one is ovulated

Answer 8

* Only 1 mature follicle is ovulated * Others degenerate = atresia -Forms from ruptured follicle -enlarges and secretes progesterone + oestrogen for 10 days -when it degenerates → Corpus albicans forms (if no fertilisation) -enlarges and maintained if pregnancy occurs

Answer 9

Many underdeveloped follicles (≤8 mm) ↑ Testosterone production → disrupted ovulation - follicles cannot fully develop so no egg is released Symptoms: Infertility, weight gain, hirsutism (excessive hair growth) ↑ Risk of: Diabetes, heart disease Affects ~1 in 5–10 women

Answer 10

- paired ~10cm long - extends from ovary to uterus transporting the oocyte Parts: 1. Infundibulum - funnel-shaped, closest to the ovary, finger-like projections called fimbriae that collect the ovum after ovulation, main function is to capture the released egg and direct it into the fallopian tube. 2. Ampulla (site of fertilization), widest and longest part 3. Isthmus -narrowest part near uterus, with thick walls Layers: -Mucosa: Simple columnar epithelium with cilia -Muscularis: Inner circular + outer longitudinal smooth muscle -Serosa- serous membrane layer * Fertilized egg travels through ~ 6 to 10 days

Answer 11

-Fertilized egg implants outside uterus (commonly fallopian tube) ○ 1 in 100 pregnancies – life threatening ○ pelvic inflammatory disease & smoking are risk factors

Answer 12

- pear shape ~7.5 cm long - hollow muscular organ that is the site of embryo implantation Regions: Fundus - large, rounded part, posterior to fallopian tubes Body- central portion Cervix - (narrow, opens to vagina) Position: Typically anteverted (leans forward above bladder)) Support: - ligaments and pelvic floor muslces supporting uterus -Broad, Round, Cardinal, Uterosacral ligaments

Answer 13

1. Broad = peritoneal fold from uterus lateral walls to wall of pelvis 2. Round ligament = extend through inguinal canals to labia majora. Embedded in broad ligament. 3. Cardinal ligament = attaches lateral pelvic wall to lateral cervix and vagina 4. uterosacral = lateral wall of uterus to sacrum

Answer 14

- backward tipping position of the uterus - can be painful but does not influence fertility -Can ‘cure’ itself after first pregnancy or surgery can be had (can go back to normal position)

Answer 15

- if muscles weaken, uterus extends inferiorly into vagina

Answer 16

1. Perimetrium – Outer external layer, serosa membrane covering the uterus 2. Myometrium – Thick smooth muscle (promotes contractions during pregnancy and menstruations), - Cervical has less muscle, more dense connective tissue so rigid & less contractile 3. Endometrium – mucous membrane Contains uterine glands and blood vessels (spiral arteries) Lined by simple columnar epithelium and lamina propria (internal layer) - thickens during menstruation to help prepare for fertilization - Functional zone gets removed during menstrual cycle if fertilization does not occur (blood) Stratum functionalis zone (external)– Changes during menstrual cycle Stratum basalis zone (internal) – Regenerates functionalis

Answer 17

- during the cycle it can eb ~8mm thick - during menstruation most of endometrium is lost - after menstruation- endometrium is ~1mm thick

Answer 18

- neck of the uterus, connects to vagina Epithelial cells: Upper: Columnar Lower: Stratified squamous Mucous glands: - acts as a protective barrier to substances from the vagina (vulnerable to pathogens, bacteria which could reach peritoneal cavity) -Becomes thinner near ovulation to allow sperm entry

Answer 19

Structure: Fibromuscular tube (~10 cm) Wall Layers: 1. Inner mucosa: Stratified squamous folded in rugae lubricates in intercourse hymen covering vaginal opening 2. Muscularis: inner longitudinal + outer circular muscle - allows vagina to enlarge in intercourse and childbirth 3. Adventitia: Outer connective tissue, anchors vagina, gateway to uterus Functions: Menstrual flow, birth canal, intercourse

Answer 20

Labia majora: Fatty skin folds, contain sweat/sebaceous glands Labia minora: Smaller skin folds around vestibule Vestibule space: Contains urethral + vaginal openings, mucous glands Clitoris: Erectile tissue, corpora cavernosa Mons pubis: Fat pad over pubic symphysis

Answer 21

Cervical epithelium = columnar (upper cervix) → squamous (lower cervix) - abnormal changes in cell shape can indicate cancer Transformation zone = site of squamous metaplasia; vulnerable to abnormal changes HPV infection linked to 70% of cervical cancer cases (new vaccinations for some variations) Diagnosed via Pap smear Treatments: Surgery, chemo, radiation

Answer 22

female vs male alternatives: labia majora = scrotum labia minora = spongy urethra vestibule = membraneous urethra bulb of vestibule = bulb of penis clitoris = glans penis ovary = testes skenes glands = prostate bartholins gland = cowpers gland

Answer 23

- puberty leads to increased release of GnRH - stimulating the anterior pituitary - FSH release -> releases oestrogen - LH release -> progesterone release (maintains endometrium) - hormone contraceptives target and suppress the LH surge rather than FSH, targetting FSH would cause infertility

Answer 24

Sensation: Detection of physical stimuli by receptors. Perception: Interpretation of sensory input by the brain. Sensation is input about the physical world obtained by our sensory receptors, and perception is the process by which the brain selects, organizes, and interprets these sensations. - perception of a sensory experience can change even though the input remains the same (different people see different things)

Answer 25

Touch Temperature (internal or external) Pain (Nociception) Proprioception (body position)

Answer 26

Vision Hearing Equilibrium (balance) Olfaction (smell) Gustation (taste)

Answer 27

- each sensory system provides the CNS with a representation of the external world - stimulus detection - sensory receptor (transducer) then either: 1. descending neurons (goal directed mechanisms) -> CNS -> integration + perception 2. afferent/ascending sensory neurons (stimulus driven mechanisms) -> CNS -> integration + perception

Answer 28

1. By Modality: (reacting to particular forms of stimuli) Chemoreceptors – chemical (smell, taste) Thermoreceptors – temperature Nociceptors – pain Mechanoreceptors – touch, pressure, vibration Photoreceptors – light (vision) 2. by distribution: - general senses (widely distributed) - special senses (limited to head) 3. by origin of stimuli Exteroceptors: Detect external stimuli Interoceptors: Detect internal environment Proprioceptors: Detect body position (muscles, joints)

Answer 29

Sensory receptors are transducers → convert stimuli to electrical signals through opening of ion gated channels Stimulus strength → affects magnitude of receptor potential. Graded potentials lead to Action Potentials in sensory neurons. - transmits voltage changes into ganglion/sensory cells Neural coding: Stimulus intensity encoded by = rate & number of APs Stimulus duration encoded by = duration of AP activity in the sensory neuron

Answer 30

-All special sensory pathways decussate (cross midline at medulla) except smell and taste. (cross info across hemispheres) -The thalamus is a relay centre with specific nuclei for each sense. Information projects from thalamus → specialised primary cortices. (specialized cortical areas) Visual: retina → thalamus → visual cortex Auditory: ear → brainstem → thalamus → auditory cortex - Inferior colliculus important in auditory processing in midbrain Somatosensory: body → spinal cord → brainstem → thalamus → somatosensory cortex

Answer 31

Receptors: Chemoreceptors in olfactory epithelium (nasal mucosa) - Olfactory receptor cells are randomly distributed in the nasal mucosa but convergence of several olfactory receptors cells onto the same glomeruli in the olfactory bulb - axons snapse with bulb directly Structure: Bipolar neurons with supporting, basal and olfactory receptor cells present Pathway: Receptor cells → Olfactory bulb → Brain (no decussation) Note: Signals go directly to cortex (bypass thalamus)

Answer 32

1. odorant molecules bind to receptor proten (G protein) on the cilia 2. depolarisation of olfactory receptor cells 3. if threshold is reached- generation of APs sent to olfactory bulb 4. in the glomerulus- receptor nerve endings excite mitral cells that forward the signal to the primary olfactory cortex 5. olfactory neurons from the olfactory nerve (cranial nerve 1)

Answer 33

- from the olfactory tract, the signal goes to the primary olfactory cortex (piriform, enthorinal cortex and amygdala) - PIR and amygdala form part of the limbic system - orbitofrontal cortex associates smells and tastes together

Answer 34

- sensory organs are taste buds located in the gustative papillae - taste buds are taste receptor cells (specialised neurons with membrane receptors sensitive to different chemical molecules) - filliform papillae do not have tastebuds - a tastebud contains 50-150 receptor cells + supporting cells - they have microvilli which extends through a pore to make contact with the tastant Tastants: Sweet, salty, sour, bitter, umami (molecules being detected) - each receptor specific to a taste - they bind to their respective receptor and excite associated neurons -> depolarisation Pathway: Cranial nerves → Medulla → Thalamus → Gustatory cortex

Answer 35

Receptors: Photoreceptors (rods/cones) in the retina - light converted into neural signals in the retina (layer of cells on inner surface at back of eye) Fovea: Only cones = high acuity Pathway: Retina → LGN (thalamus) → Visual cortex (No brainstem relay)

Answer 36

- both contain photopigments (rodopsin for rods and opsins for cones) which undergo a chemical change when they absorb light - three cones with different opsins( S, M, L) - rods responsible for night vision and grey shades - cones for colour vision

Answer 37

three neuron chain in the retina: photoreceptors -> bipolar cells -> retinal ganglion cells - photoreceptors hyperpolarized by light - retinal ganglion cells send APs along their axon forming the optic nerve -Light has to passed through all layers of eye to get to the light receptors -Bipolar cells cause depolarisation of retinal ganglion cells

Answer 38

axons in the retina project to: 1. primary visual cortex (V1) = through the LGN, a thalamic relay. half of fibres coming from one eye cross at the optic chiasm and project to contralateral LGN. other half remain ipsilateral 2. superior colliculus = control of eye movements and co-ordination with auditory information 3. suprachiasmatic nucleus = control of circadian rhythms. - sensory info projecting to all 3 of these areas.

Answer 39

Peripheral Organ: Ear (external, middle, inner) Receptors: Hair cells in the cochlea Mechanism: Sound waves → mechanical vibrations → fluid motion → hair cell stimulation Pathway: Cochlear nerve → Brainstem → Thalamus → Auditory cortex

Answer 40

1. outer 2. middle (tympanic membrane and auditory ossicles) 3. inner ear ( cochlea, 3-semi circular canals and vestibule) - inner ear uses hair cells to detect stimuli for hearing in the cochlea to send neural signals to brain through vestibulocochlear nerve - sound waves hit onto tympanic membrane causing the auditory ossicles to vibrate -> amplification of sound wave

Answer 41

- filled with fluid and contais hair cells for transduction of mechanical wave into an electrical signal - organ of corti is on top of basilar membrane (hair cells, supporting cells and tectorial membrane) - hair cells have stereocilia

Answer 42

1. sound waves travel towards tympanic membrane which vibrates 2. auditory ossicles conduct the vibration into the inner ear 3. movement of the oval window applies pressure to the perilymph 4. pressure waves disorts basilar membrane 5. hair cells are pushed against the tectorial membrsne 6. bending of stereocillia 7. discharge of action potentials basilar membrane: mechanical sound analyser - different regions vibrate according to the frequency of the sound wave

Answer 43

Organ: Inner ear (shared with auditory system) Receptors: Hair cells with stereocilia (mechanoreceptors) Static balance: Utricle & Saccule (head position) Dynamic balance: Semicircular canals (head movement) Pathway: Vestibular nerve sends signal to → Brainstem & Cerebellum (vestibular system)

Answer 44

- saccule and utricule respond to acceleration in straight lines such as gravity - hair cells are located in the base of each semicircular canal and contain carbonate crystals - hairs project into cupula where they monitor angular acceleratio/ deacceleration from rotation - head tilt -> bending of stereocilia

Answer 45

1. spinal cord = control of body posture 2. cerebellum = co-ordination of movement 3. colliculus superior = control of eye movements 4. primary somatosensory cortex = perception of self-movement

Answer 46

- divide indefinitely but remain in undifferentiated state - it's the daughter cells that can differentiate into many specilaised cell types hayflick limit -> number of times a normal cell can divide before dying.

Answer 47

1. embryonic 2. umbilical 3. adult

Answer 48

potent = potential to differentiate totipotent = greatest differentiation potential, capable of producing all the specialized cell types in an organism, including both embryonic and extraembryonic tissues pluripotent = can become any cell in the organism except the placenta multipotent = capacity to become multiple cell types within a family of cells unipotent = one type of cell

Answer 49

Source: Inner cell mass of the blastocyst (~5 days post-fertilisation - morula becomes blastocyst at day 5 with inner and outer layer(trophoblast) - outer layers function is to nourish the inner layer Potency: either: Pluripotent – e.g blastocyst totipotent- e.g morula which is the early staged embryo formed 72hrs after fertilisation properties: - Embryo inner cell mass can differentiate into > 200 cell types - Divide indefinitely in culture -Retain pluripotency -Differentiation not yet fully controllable (telling them to differentiate into specific types) Clinical Application: -Potential for regenerative medicine -harvested for reseach and for treatments -Ethical concerns (blastocyst destruction) -Research into cloning for patient-matched therapies - ethical consideration of when does life begin?

Answer 50

Source: umbilical cord blood at birth Potency: Pluripotent or Multipotent – limited compared to ESCs clinical application: can we store cord blood to treat future conditions? Treats: Leukaemia, lymphoma, sickle cell, immune disorders Cord blood banks: NHS has a public bank; private banking use has limited evidence for doing so Stored altruistically; could be life-saving

Answer 51

Source: Many adult tissues (e.g. bone marrow, skin, intestine) Potency: Multipotent (haemopoietic/blood) or Unipotent (in the skin) Properties: -Can self-renew throughout life (expand lifespan) -unlimited divisions within lifespan -Difficult to identify; no specific markers - exisit in many tissue but are low in number -Slow division rate -1 stem cell per ~100,000 cells - irreversible development Clinical Application: Bone marrow transplants for blood cancers (e.g. leukaemia) Used to replenish tissues like blood and intestinal lining

Answer 52

* When a stem cell divides the symmetric division of one stem cell gives rise to two daughter stem cells * Each subsequent daughter stem cell then has a choice * Remain a stem cell (self-renewal)? * Become a progenitor cell & commits to differentiation ? * This may be described as asymmetrical fate Is this decision based upon; * Extrinsic factors – i.e. environment? * Intrinsic factors – i.e. inherited factors? Asymmetrical Division: One daughter cell self-renews Other differentiates (progenitor) -Can shift to symmetrical division in injury -Used to repair damaged tissue

Answer 53

Controlled by: Molecular signals Growth factors Integrins Division rate and number of them Importance: Avoids uncontrolled proliferation → cancer * Genes that control self-renewal rather than differentiation are likely to be candidate oncogenes * Tumors seem to have their own stem cells and it is these that can lead to return of cancer * These need to be targeted to ensure recovery

Answer 54

= they are adult cells reprogrammed into embryonic-like state which can differentiate into any cell type for therapeutic purposes Method: - a virus is used to introduce genes to encode transcription factors (e.g. Oct4, Sox2, Klf4, c-myc) - this reprogrammes the fibroblast to return to pluripotent state (like ESCs) Uses: Disease modelling Drug screening Potential future therapies (not yet in clinics) Advantage: No embryo destruction Risk: Tumor formation

Answer 55

Claimed: Cell stress (e.g. low pH, toxins, acid) reprograms adult cells to induce pluripotency Study (Obokata 2014): publication retracted due to misconduct - not replicable - They used the spleen lymphocytes of neonatal mice and subjected the cells to stress of pH 5.7 for 30 minutes

Answer 56

- bone marrow transplants (first use) - in leukemia (Disease whereby the hematopoietic stem cells in the bone marrow produce too many (often abnormal) white blood cells) treatment: * Cell killing drugs (chemotherapy) target fast dividing cells * Often systemic effects so can target non-cancerous fast dividing cells such as hair, skin too (hair loss) * Irradiation to give targeted treatment to damage cell DNA and stop cell replication After this, patients will require bone marrow transplant to replace haematopoeitic stem cells - can be harvest from red bone marrow (red and white blood cells + platelets)

Answer 57

- a cell is taken from patient - combined with donor fertilised egg - nucleus removed from egg and replaced with nucleus from patient cell - egg is stimulated to divide and the resulting embryo carries the patients genetic material - ethical opposition - potential use for insulin, parkinsons, alzhiemiers - a technique used to create embryonic stem cells that are genetically identical to a patient. - The process involves removing the nucleus from a patient's cell and placing it into an egg cell that has had its own nucleus removed, then allowing the egg to develop into a blastocyst from which stem cells are extracted.

Answer 58

Pulmonary Hypertension: High blood pressure in the pulmonary circulation can lead to right-sided heart failure. Key Mechanism: Endothelial cells help relax blood vessels. Targeting this interaction between endothelium and vascular smooth muscle can be effective. - hyperpolarization can bring about this relaxation

Answer 59

Nitric Oxide (NO): Produced in the endothelium, helps relax blood vessels. (more used in pulmonary hypertension) Riociguat: Used in chronic thromboembolic pulmonary hypertension (CTEPH) following surgery and in combination with endothelin receptor antagonists for pulmonary arterial hypertension (PAH). dual mechanism of action: 1. stimulates sGC in NO mode of action, enhancing cGMP synthesis, producing vasodilation 2. improves pulmonary hemodynamics and prevents adverse structural remodelling

Answer 60

Endothelial cells produce prostacyclin that activates adenylate cyclase (AC) in smooth muscle to promote relaxation. prostacyclin receptor agonists: e.g epoprostenol, treprostinil - used to treat hypertension - They activate prostacyclin receptors (IP receptors) on vascular smooth muscle cells, leading to vasodilation and reduced pulmonary vascular resistance. (mimicing the action)

Answer 61

-Used in pulmonary hypertension. -Orenitram (US) and in UK clinical trials (tablets not yet available).

Answer 62

Endothelin 1: Excess production by endothelium causes vasoconstriction and side effects (e.g., hepatotoxicity). - most potent vasocontrictor ever isolated example endothelin receptor blockers 1. Sitaxentan: Was withdrawn due to fatal liver damage (2010). 2. bosentan: non-selective endothelin antagonist

Answer 63

- inactivates MLC phosphatase -> increased levels of phosphorylated MLC -> vascular smooth muscle contraction - inhibits phosphorylation of myosin chain - activity is switched on when Rho-GTP binds to kinase coiled-coin domain examples: 1. Fasudil (Available in Japan/China): Blocks the rho-kinase enzyme, preventing contraction and allowing muscle relaxation. 2. azaindole-1: is a precursor for fasudil

Answer 64

Nitric Oxide (NO) Dysfunction: NO becomes less effective when endothelial nitric oxide synthase (eNOS) is uncoupled. Recoupling eNOS can restore proper function. - eNOS is critical in maintaining normal vasculature Nitric oxide not working as well as it should -> fixing this -> regulate dilation and constriction When enzyme doesn’t have what it needs, becomes uncoupled -> not producing nitric oxide We want recoupling of enzyme so it functions properly

Answer 65

- free radical interactions - protein binding - lipid binding - nucleic acids - oxidation - nitric oxide synthesis -Conversion 15NG-L-arginine to 15NO -Different types of NO in different locations -L-arginine is a main one, but in plentiful supply

Answer 66

Minoxidil: Opens potassium channels, leading to hyperpolarization and vessel dilation. Inward rectifier potassium channels (Kir channels) are a type of potassium channel that allow potassium ions (K+) to flow more easily into the cell than out of it mode of action: 1. K+ channel openers open Katp 2. enhance K+ efflux 3. membrane hyperpolarization 4. decreased calcium entry 5. reduced intracellular calcium 6. smooth muscle relaxation

Answer 67

-used to treat and reduce chest pain caused by angina. It works by relaxing and widening your blood vessels and increasing the blood and oxygen supply to your heart. - decreases preload and afterload - well absorbed orally

Answer 68

A single treatment that could act as a “cure” for genetic conditions associated with cardiovascular diseases. - directly contacts the gene causing the problem - targetting and removing the bad gene associated with the problem - harder to identify if more than one gene is the issue Delivery methods: Viral or non-viral (e.g., liposomes, electroporation, etc.).

Answer 69

Non-Viral molecular Methods: Liposomes, Electroporation, Salt-shock (CaCl2) – often inefficient and transient. Viral Methods: * Many virus types available with varying: * Target specificity * Dividing/Non-dividing cells * Cassette size * Transfection stability * Genome insertion areas * Efficiency * The virus must not make unwanted modifications/ harm to patient common virus types: Adenovirus, Adeno-associated viruses, Retroviruses, Lentiviruses – need careful selection to avoid unwanted effects (e.g., cancer, viral harm). Deliver directly: -Virus may get into cells where you don’t want it to -The vector can be used to try take it exactly where you want it to go (cell based delivery)

Answer 70

- gene therapy = directly targets the gene causing the problem Viral Methods =We hijack viruses to deliver the good gene into human cells. non viral methods = altering DNA directly Problems / Challenges Hard to target only the diseased cells Risk of immune response to virus If more than one gene is involved in the disease, it’s harder to treat Expensive and technically demanding - the lentivirus allow large transgene cassettes to be stably transfected in vivo - larger cassette sizes allow for incrporation of transcriptional control systems

Answer 71

ACE2: Converts angiotensin I to smaller peptides that help reduce blood pressure and remove excess angiotensin I and II.

Answer 72

Low Therapeutic Index: Risk of toxicity. Toxicity Symptoms: Nausea, vomiting, color vision changes, cardiac arrhythmias. Interactions: Diuretics (reduce K+), amiodarone, verapamil, quinidine (increase digoxin concentration). -> increase plasma concentrations

Answer 73

Levosimendan: - binds to troponin c at high intracellular calcium Sensitizes cardiac muscle to calcium, improving contraction during systole. (contraction of heart) Also acts as a vasodilator and PDE inhibitor at higher concentrations. Clinical Use: Phase III trials in the UK, showing reduced mortality in heart failure patients. - given post op at end of cardiac surgery Benefits: Increases force of contraction and reduces afterload.

Answer 74

Inflammation plays a major role in heart failure and its progression. - a pro-inflammatory cytokine is elevated in heart failure causing negative effects example drugs- anakinara, canakinumab Monoclonal Antibodies: Used to block inflammatory pathways and reduce damage, preventing further heart attacks.

Answer 75

Levosimendan: Phase III trials for heart failure. Treprostinil: Pulmonary hypertension, clinical trials in the UK. Riociguat: Used in pulmonary hypertension.

block 9- special systems Flashcards

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