Concise Flashcards Sem 2A
Name the phases of the cell cycle.
Phases of Cell Cycle
-
Interphase
- G1 – Cell grows rapidly, carries out normal activities and duplicates organelles
- S – DNA replication
- G2 – Cell grows and prepares for mitosis o G0 – a state of non-division (quiescence)
- Mitosis - cell division
- Cytokinesis – splitting of cells following mitosis
Outline the process of DNA replication.
DNA Replication
- Topoisomerase unwinds the DNA
- Helicase separates the two strands of DNA
-
Polymerases are protein complexes responsible for replicating DNA
- Polymerases can only extend nucleic acid, not create new sequences – primase is needed
- DNA Pol α – lays down 5’ primer sequence
- DNA Pol δ – continues from Pol α
- Replication is 5’ to 3’ – but the lagging strand is 3’ to 5’ – need to process lagging strand as well
- The leading strand is replicated continuously
- The lagging strand is replicated in short sequences (okazaki fragments) that are joined by DNA ligase
Compare and contrast mitosis and meiosis in 8 ways.
Outline the process of mitosis - 6 stages.
Mitosis
-
Prophase
- Compaction of chromatin to form chromosomes
- Formation of the mitotic spindle
-
Prometaphase
- Defined by dissolution of the nuclear membrane
- Centromeres of chromatids attach to kinetochores (spindle)
- Chromosomes start to be aligned along the midline
-
Metaphase
- Chromosomes are aligned in the centre of the spindle
-
Anaphase
- Chromatids separate and are drawn to the poles
-
Telophase
- Chromosomes cluster at the poles and nuclear membranes form at either pole surrounding the clusters
-
Cytokinesis
- Not formally part of mitosis/meiosis
- Cells separate at midpoint between poles → daughter cells
List 5 criteria for a good screening test.
Criteria for a Good Screening Test
- The condition should be an important health problem
- The test should be safe and non-invasive
- The test should be precise with high sensitivity and specificity
- The test should be cost-effective
- There should be a treatment available for the condition
What is the Triple Test?
What 3 things does it test for?
What do the results look like for Trisomy 13, 18, 21?
Triple Test
- Also called triple screen, the Kettering test or the Bart’s test
- An investigation performed during pregnancy in the 2nd trimester to classify a patient as either high-risk or low-risk for chromosomal abnormalities.
- Measures 3 serum levels:
- β-human chorionic gonadotropin (hCG) – maintains corpus luteum in early pregnancy
- α-fetoprotein (AFP) – plasma protein that binds oestradio
- Unconjugated oestriol (UE3) – derivative of pregnalone formed by the adrenal gland
What 4 main conditions does the postnatal heelprick test for?
Heelprick Test
- Cystic Fibrosis
-
Phenylketonuria (PKU)
- Deficiency in phenylalanine hydroxylase – no conversion of Phe → Tyr
- Accumulated Phe converted to phenylpyruvate – causes mental retardation
- Treatment – low Phe diet; tetrahydrobiopterin
-
Galactosaemia
- Deficiency in metabolism of galactose
- Speech deficits, ataxia, cataracts
-
Hypothyroidism
- Deficiency in genes involved in thyroid function
- Sleepiness, poor muscle tone, jaundice
Outline 3 different samples that can be taken from a foetus to test for genetic disorders.
When are each of them performed?
What is their associated risk of miscarriage?
Fetal Genetic Testing
- Chorionic Villus Sampling → chorionic villus (10-12 weeks)
- Amniocentesis → amniotic fluid (16-20 weeks)
- Cordocentesis → fetal cord blood (~17 weeks)
What is euploidy and what 3 mechanisms can cause it?
Euploidy = The addition or loss of full sets (23) of chromosomes - results in an exact multiple of haploid chromosomes
- Haploidy (n) – 23 chromosomes
- Triploidy (3n) – 69 chromosomes
- Tetraploidy (4n)– 92 chromosomes
Mechanisms:
- Polyspermy (two sperm fertilising an ovum)
- Fusing of an ovum with a polar body
- Nondisjunction in the zygote or other somatic cells
Explain 3 types of aneuploidy.
Types of aneuploidy
-
Autosomal aneuploidy
- All autosomal monsomies are lethal
- Most autosomal trisomies are lethal
- Trisomy 16 is the commonest (1/3) but is never seen in live birth
- Trisomy 13 (Patau), 18 (Edwards) and 21 (Down) are all viable
-
Sex chromosome aneuploidy
- More common than autosomal – milder phenotypes
- Turner Syndrome (monosomy X) - 1/1000 births
- Phenotypic female w/ webbed neck, angled elbows, usually sterile
- Kleinfelter syndrome (XXY) - 1/800 births
- Phenotypic male, ↑X chromosomes → ↑female characteristics
- 47XXX – fertile female, asymptomatic
- XYY syndrome – mild phenotype
-
Mosaicism
- Some cells have a normal number of chromosomes while others are aneuploid
- Phenotypic consequences are difficult to predict
Name 6 contents of the superficial perineal pouch.
Name 5 contents of the deep perineal pouch.
Superficial Perineal Pouch
- Ischiocavernosis muscle
- Bulbospongiosus muscle
- Superficial transverse perineal muscle
- Crura of clitoris (F) / crura of penis (M)
- Bulb of vestibule (F) /bulb of penis (M)
- Bartholin’s glands (F)
Deep Perineal Pouch
- Deep transverse perineal muscle
- External urethral sphincter muscle
- Proximal urethra (F) / membranous urethra (M)
- Bulbourethral gland (M)
- Vagina (F)
Outline the muscles of the pelvic diaphragm.
Pelvic Floor Muscles
-
Levator Ani – three parts
- Pubococcygeus – pubis → anococcygeal ligament
- Puborectalis - L pubis → R pubis (surround prostate/vagina)
- Iliococcygeus - obturator membrane → coccyx & anococcygeal ligament
- Coccygeus (ischococcygeus) – ischial spine → lateral coccyx/L5 vertebra
List the 5 contents of the spermatic cord.
Contents of the Spermatic Cord
- Ductus deferens
- Arteries
- Testicular artery
- Cremasteric artery
- Artery of ductus deferens
- Pampiniform plexus
- Autonomic nerves
- Genital branch of the genitofemoral nerve 6. Lymphatic vessels
List the 7 layers of the scrotum.
Layers of the Scrotum
- Skin
- Dartos fascia & dartos muscle
- External spermatic fascia
- Cremaster muscle
- Cremasteric fascia
- Internal spermatic fascia
- Tunica vaginalis - parietal and visceral layers
Outline the path of sperm from the seminiferous tubules to the penile urethra (10).
Path of Sperm from seminiferous tubules to the penile urethra
- Seminiferous tubules
- Straight tubules
- Rete testis
- Efferent ductules
- Epididymis
- Ductus deferens
- Ejaculatory Duct
- Prostatic Urethra
- Membranous urethra
- Penile Urethra
Outline the blood supply to the ovaries, uterus, vagina and external genitalia.
Describe the 3 cells that make up the seminiferous tubules and surrounding interstitial tissue.
Cells of the seminiferous tubules and surrounding interstitial tissue.
-
Sertoli cells (sustentacular) cells – within the germinative epithelium
- Supportive function
-
Spermatogenic cells – move from the basal compartment to lumen
- Spermatogonia
- Primary spermatocytes
- Secondary spermatocytes
- Spermatids & spermatozoa
- Leydig cells (interstitial cells) – produce testosterone
List 3 effects of oestrogen and 4 effects of progesterone.
Effects of Estrogen
- Growth of uterus, mammary ducts and reproductive tract tissues
- Female secondary sex characteristics
- Bone metabolism & maturation
Effects of Progesterone
- Prepares the body for pregnancy
- Modifies/antagonises effects of oestrogen
- Increases basal body temperature
- Develops alveoli of breasts
Outline the 3 phases of the ovarian cycle.
Phases of the Ovarian cycle
Follicular Phase – Days 1-14
- Menstrual phase (day 1-5)
- ↑ FSH
- 10-25 follicles → secondary follicles
- Pre-ovulatory phase (days 6-14)
- ↑oestrogen from follicles → ↓FSH (negative feedback)
- LH surge (positive feedback)
- One follicle predominates, all other follicles undergo atresia
Ovulation – Day 14
- LH surge → ↑PGs → ↑blood flow to follicle → degradation of ovary wall
- The oocyte is taken up by the uterine tube and is viable for 8 hours
Luteal Phase – Days 14-28
- Granulosa and theca interna cells multiply to fill the antrum → corpus luteum – responsive to LH
- As LH decreases the corpus luteum begins to atrophy
Outline the 3 phases of the menstrual cycle.
Phases of the menstrual cycle
Menstruation – Day 1-~4
- ↓Oestrogen & progesterone → prostaglandin release → constriction of endometrial vessels → ischaemia → contractions of the myometrium
- Ischaemia → degeneration of endometrial glands, stroma, vessels and tissue
- Blood, serous fluid and degenerated endometrial tissue are discharged
Proliferative Phase – Day 4-14
- ↑Oestrogen → regrowth/proliferation of endometrial tissue and blood vessels
Secretory Phase – Day 14-28
- ↑Progesterone → glycogen accumulation
- ↑Progesterone → uterine hypertrophy
- ↑Progesterone →↑basal body temperature
List some effects of testosterone on tissues.
Effects of Testosterone on Tissues
- Fetus: sex determination
- Puberty: male 2° sexual characteristics
- Spermatogenesis
- Liver: ↑VLDL, ↑LDL, ↓HDL
- Bone and muscle growth
- CNS effects
- Prostate/hair follicles: T → 5α-DHT
List 7 functions of Sertoli cells.
Sertoli Cells - Functions
- Maintain tight junctions (blood-testes barrier)
- Nourish germ cells and provide signals for sperm differentiation
- Phagocytosis
- Secrete fluid
- Secrete Androgen-binding protein (ABP)
- Binds to testosterone in lumen and maintains high concentration near tubule
- Secrete inhibin - presence of excess spermatids → ↑inhibin → ↓FSH release → ↓spermatogenesis
- Convert testosterone to estrogen (aromatase)
List the embryological origins of male and female reproductive organs, and what they develop into.
Embryological origins of male and female reproductive organs
-
Gonadal Ridges
- Male → Testis
- Female → Ovaries
-
Müllerian duct (paramesonephric duct)
- Male → Appendix testis, Prostatic utricle
- Female → Fallopian Tubes, Uterus, Upper vagina
-
Wolffian duct (mesonephric duct)
- Male → Rete testis, Epididymis, Vas deferens, Seminal vesicle
- Female → Rete ovarii
-
Urogenital sinus
- Male → Bladder & urethra, Prostate
- Female → Bladder & Urethra, Skene’s Glands, Lower vagina
-
Gubernaculum
- Male → Scrotal ligament
- Female → Round ligament of uterus
Outline the process of spermatogenesis.
Spermatogenesis
-
Mitosis (25 days) – also known as spermatocytogenesis
- Spermatogonia → primary spermatocytes
- One daughter cell becomes a spermatocyte while the other stays a spermatogonia
-
Meiosis (28 days)
- Meiosis I: primary spermatocytes → secondary spermatocytes
- Meiosis II: secondary spermatocytes → spermatids
-
Spermiogenesis (21 days)
- Differentiation: spermatids → spermatozoa
- Golgi phase – acrosomal granules form in the golgi and become an acrosomal vesicle
- Cap phase – acrosomal vesicle moves to the top of the cell
- Acrosome phase – elongation of the cell
- Maturation – disconnection from sertoli cells
List the embryological origins of male and female external genitalia, and what they develop into.
Embryological origins of male and female external genitalia
-
Labioscrotal folds
- Male → Scrotum
- Female → Labia majora
-
Urogenital folds
- Male → Spongy/penile urethra
- Female → Labia minora
-
Genital tubercle
- Male → Bulb of penis, Glans penis, Crura of penis
- Female → Bulb of vestibule, Glans clitoris, Crura of clitoris
-
Prepuce
- Male → Foreskin
- Female → Clitoral hood
Outline how the combination contraceptive pill works?
3 advantages & 1 disadvantage?
Combined Oral Contraceptive Pill
Mechanism of Action
- A combination of oestrogen and progesterone
- Prevents ovulation by inhibiting gonadotropin secretion from the pituitary and hypothalamus
- Progesterone inhibits LH secretion - no LH surge → no ovulation
- Oestrogen inhibits FSH secretion - provides stability to the endometrium → ↓irregular/unwanted bleeding
- A cyclic regimen involves the contraceptive being taken for a certain number of days followed by a break (no pills/placebo) in order for withdrawal bleeding to stimulate menstruation
Advantages
- Less need for abortion/sterilisation
- Less flow, dysmenorrhoea, anaemia
- Less cancers
Disadvantages = Increase in clotting factor production (hypercoagulability) → ↑chance of thrombosis & MI
Outline some FEMALE causes of infertility.
Infertility Causes - Females
Ovulation Disorders
- Hypothalamic/pituitary problems - low FSH/LH & low oestrogen
- Ovarian problems - polycystic ovarian syndrome, ovarian failure
- Uterine or outflow tract disorders
Cervical Abnormalities
- Stenosis – from HPV, tumours etc.
- Inadequate mucus
Tubal Disease
- Pelvic inflammatory disease (PID) - untreated chlamydia/gonorrhoea
- Ruptured appendicitis
- Endometriosis - presence of endometrial glands and stroma outside of the uterus
- Pelvic adhesions
- Previous abortion
- Ciliary dysfunction
Other - stress, psychological, under-nutrition, under/overweight, ageing
Outline some MALE causes of infertility.
Infertility Causes - Males
-
Primary Hypogonadism (Defects in the gonads →↑FSH/LH)
- Kleinfelter’s syndrome
- Orchitis
- Irradiation
- Drugs – chemotherapy, alcohol, smoking
- Trauma (e.g. testicular torsion)
-
Secondary Hypogonadism (Defects in hypothalamus/pituitary → ↓FSH/LH)
- Kallman syndrome (congenital lack of GnRH → also lack of smell)
- Drugs – e.g. marijuana → ↓GnRH
- Pituitary trauma or tumours
-
Sperm Transport Disorders
- Ciliary dysfunction, retrograde ejaculation, impotence
- Cystic fibrosis (lack of vas deferens)
- Anti-sperm antibodies
- Other - stress, psychological, idiopathic
Summarise the process of In Vitro Fertilisation.
(8 steps)
In Vitro Fertilisation - Process
- Stimulation of ovaries - daily FSH injections (may follow suppression with GnRH to improve efficacy)
- Maturing of eggs/induction of ovulation – with an hCG injection
- Collection of eggs – ultrasound guided oocyte retrieval
- Insemination – may involve Intra-cytoplasmic sperm injection (ICSI) – sperm cell injected into oocyte
- Culture & assessment of embryos
- Transfer of embryo – 1 or 2 of the ‘best’ embryos are selected & transferred, the rest can be frozen
- Awaiting results – stressful time for the couple
- Progesterone support & after care – in the 2 week period following embryo transfer
Describe why you would prescribe the drug clomiphene.
Clomiphene
Clomiphene is used to induce ovulation (egg production) in women who do not produce ova (eggs) but wish to become pregnant (infertility). Clomiphene is in a class of medications called ovulatory stimulants. It works similarly to estrogen, a female hormone that causes eggs to develop in the ovaries and be released.
- Used in the case of inadequate oocyte production or abnormal oocytes
- An oestrogen antagonist that reduces negative feedback on the female reproductive axis
- Leads to ↑GnRH and FSH → ↑follicle development
List 10 options for patients experiencing infertility.
Options for patients experiencing infertility
- Lifestyle advice
- Surgery
- Artificial insemination
- Fertility medication
- In vitro fertilisation
- ZIFT/GIFT = Gamete/Zygote Intrafallopian Transfer
- Hormone therapy
- Surrogates
- Donor sperm
- Donor Oocytes
Name the bones of the tarsus.
Bones of the tarsus
- Calcaneous (heel bone)
- Talus (ankle bone)
- Cuboid
- Navicular
- 3 cuneiform
Outline the arterial supply to the lower limb.
List the movements of the upper limb and the major muscles involved as well as their nerve roots and peripheral nerves.
Outline the venous drainage of the lower limb.
Venous Drainage of the Lower Limb
- Veins accompany arteries, except for the superficial veins
- Superficial veins
- Great saphenous vein is formed by the dorsal veins of the hallux and dorsal veinous arch
- Small saphenous vein is formed by the dorsal veins of the small toe and dorsal veinous arch
- Both saphenous veins join with the femoral artery
Name some landmarks explaining the dermatomes of the lower limb.
- L1 – below inguinal ligament
- L2 – upper anterior thigh
- L3 – middle anterior thigh → medial knee
- L4 – anterior knee → medial ankle
- L5 – dorsum of foot
- S1 – lateral ankle
- S2 – popliteal fossa in midline
- S3 – ischial tuberosity
Outline the 3 types of joints.
Types of Joints
-
Fibrous Joints
- United by fibrous tissue
- Sutures e.g. sutures of the skull
- Gomphosis – peg-like processes fitting into a socket e.g. the root of a tooth
- Syndesmosis – bone united with a sheet of fibrous tissue (ligament/fibrous membrane) e.g. radioulnar joint
-
Cartilagenous Joints
- United by hyaline cartilage or fibrocartilage
- Synchrondrosis (1° cartilaginous joint) - hyaline cartilage; permits movement in early life and growth of bone e.g. epiphyseal plates of long bones
- Symphysis (2° cartilaginous joint) – fibrocartilage; strong joints e.g. intervertebral discs
-
Synovial Joints
- Consist of a joint cavity enclosed by an articular capsule containing synovial fluid
- Articular cartilage covers the articular surfaces of the bones
- Can move in one plane (uniaxial), two planes (biaxial) or three planes (multiaxial)
List the movements of the lower limb and the major muscles involved as well as their nerve roots and peripheral nerves.
Name the types of synovial joints and the number of axes they have, giving an example for each.
Types of Synovial Joints
- Gliding/ Plane → Uniaxial - eg. Sacroiliac
- Hinge → Uniaxial - eg. Elbow
- Pivot/ Trochoidal → Uniaxial - eg. Radioulnar
- Saddle → Biaxial - eg. Sternoclavicular
- Condyloid/ Ellipsoidal → Biaxial - eg. Radiocarpal
- Ball & Socket/ Spheroidal → Multiaxial - eg. Hip
Give some basic information regarding osteoarthritis and rheumatoid arthritis.
Osteoarthritis (OA)
- Wear and tear - loss of articular hyaline cartilage with proliferation of new
- bone and remodelling of the joint
- Not associated with inflammation
- Tends to affect weight-bearing joints
- Primary OA is idiopathic – a combination of mechanical, metabolic, genetic and constitutional factors
- Secondary OA has an obvious cause such as trauma
Rheumatoid Arthritis (RA)
- Autoimmune – infiltration of the synovial membrane with lymphocytes, plasma cells and macrophages
- Associated with joint inflammation
- Clinical features include morning stiffness, arthritis in joint areas, rheumatoid nodules and radiological changes