Concise Flashcards Sem 2A
1
Q
Name the phases of the cell cycle.
A
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
2
Q
Outline the process of DNA replication.
A
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
3
Q
Compare and contrast mitosis and meiosis in 8 ways.
A
4
Q
Outline the process of mitosis - 6 stages.
A
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
5
Q
List 5 criteria for a good screening test.
A
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
6
Q
What is the Triple Test?
What 3 things does it test for?
What do the results look like for Trisomy 13, 18, 21?
A
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
7
Q
What 4 main conditions does the postnatal heelprick test for?
A
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
8
Q
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?
A
Fetal Genetic Testing
- Chorionic Villus Sampling → chorionic villus (10-12 weeks)
- Amniocentesis → amniotic fluid (16-20 weeks)
- Cordocentesis → fetal cord blood (~17 weeks)
9
Q
What is euploidy and what 3 mechanisms can cause it?
A
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
10
Q
Explain 3 types of aneuploidy.
A
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
11
Q
Name 6 contents of the superficial perineal pouch.
Name 5 contents of the deep perineal pouch.
A
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)
12
Q
Outline the muscles of the pelvic diaphragm.
A
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
13
Q
List the 5 contents of the spermatic cord.
A
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
14
Q
List the 7 layers of the scrotum.
A
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
15
Q
Outline the path of sperm from the seminiferous tubules to the penile urethra (10).
A
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
16
Q
Outline the blood supply to the ovaries, uterus, vagina and external genitalia.
A
17
Q
Describe the 3 cells that make up the seminiferous tubules and surrounding interstitial tissue.
A
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
18
Q
List 3 effects of oestrogen and 4 effects of progesterone.
A
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
19
Q
Outline the 3 phases of the ovarian cycle.
A
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
20
Q
Outline the 3 phases of the menstrual cycle.
A
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
21
Q
List some effects of testosterone on tissues.
A
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
22
Q
List 7 functions of Sertoli cells.
A
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)
23
Q
List the embryological origins of male and female reproductive organs, and what they develop into.
A
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
24
Q
Outline the process of spermatogenesis.
A
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
25
List the embryological origins of male and female external genitalia, and what they develop into.
_Embryological origins of male and female external genitalia_
1. **Labioscrotal folds**
* Male → Scrotum
* Female → Labia majora
2. **Urogenital folds**
* Male → Spongy/penile urethra
* Female → Labia minora
3. **Genital tubercle**
* Male → Bulb of penis, Glans penis, Crura of penis
* Female → Bulb of vestibule, Glans clitoris, Crura of clitoris
4. **Prepuce**
* Male → Foreskin
* Female → Clitoral hood
26
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**
1. Less need for abortion/sterilisation
2. Less flow, dysmenorrhoea, anaemia
3. Less cancers
**Disadvantages** = Increase in clotting factor production (hypercoagulability) → ↑chance of thrombosis & MI
27
Outline some FEMALE causes of infertility.
_Infertility Causes - Females_
**Ovulation Disorders**
1. Hypothalamic**/**pituitary problems - low FSH/LH & low oestrogen
2. Ovarian problems - polycystic ovarian syndrome, ovarian failure
3. Uterine or outflow tract disorders
**Cervical Abnormalities**
1. Stenosis – from HPV, tumours etc.
2. Inadequate mucus
**Tubal Disease**
1. Pelvic inflammatory disease (PID) - untreated chlamydia/gonorrhoea
2. Ruptured appendicitis
3. Endometriosis - presence of endometrial glands and stroma outside of the uterus
4. Pelvic adhesions
5. Previous abortion
6. Ciliary dysfunction
**Other** - stress, psychological, under-nutrition, under/overweight, ageing
28
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
29
Summarise the process of In Vitro Fertilisation.
(8 steps)
_In Vitro Fertilisation - Process_
1. **Stimulation** of ovaries - daily FSH injections (may follow suppression with GnRH to improve efficacy)
2. **Maturing** of eggs/induction of ovulation – with an hCG injection
3. **Collection** of eggs – ultrasound guided oocyte retrieval
4. **Insemination** – may involve Intra-cytoplasmic sperm injection (ICSI) – sperm cell injected into oocyte
5. **Culture** & assessment of embryos
6. **Transfer** of embryo – 1 or 2 of the ‘best’ embryos are selected & transferred, the rest can be frozen
7. Awaiting results – stressful time for the couple
8. Progesterone **support** & after care – in the 2 week period following embryo transfer
30
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
31
List 10 options for patients experiencing infertility.
**Options for patients experiencing infertility**
1. Lifestyle advice
2. Surgery
3. Artificial insemination
4. Fertility medication
5. In vitro fertilisation
6. ZIFT/GIFT = Gamete/Zygote Intrafallopian Transfer
7. Hormone therapy
8. Surrogates
9. Donor sperm
10. Donor Oocytes
32
Name the bones of the tarsus.
**Bones of the tarsus**
1. Calcaneous (heel bone)
2. Talus (ankle bone)
3. Cuboid
4. Navicular
5. 3 cuneiform
33
Outline the arterial supply to the lower limb.
34
List the movements of the upper limb and the major muscles involved as well as their nerve roots and peripheral nerves.
35
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
36
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
37
Outline the 3 types of joints.
_Types of Joints_
1. **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
2. **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
3. **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**)
38
List the movements of the lower limb and the major muscles involved as well as their nerve roots and peripheral nerves.
39
Name the types of synovial joints and the number of axes they have, giving an example for each.
_Types of Synovial Joints_
1. **Gliding/ Plane** → Uniaxial - eg. Sacroiliac
2. **Hinge** → Uniaxial - eg. Elbow
3. **Pivot/ Trochoidal** → Uniaxial - eg. Radioulnar
4. **Saddle** → Biaxial - eg. Sternoclavicular
5. **Condyloid/ Ellipsoidal** → Biaxial - eg. Radiocarpal
6. **Ball & Socket/ Spheroidal** → Multiaxial - eg. Hip
40
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
41
Give some information regarding Osgood-Schlatter disease.
_Osgood-Schlatter Disease_
* Swelling of the tibial tuberosity due to rapid growth and increased physical activity, particularly in boys having a pubertal growth spurt – rarely persists beyond the growing stage
* Growth & activity →↑force of patellar tendon on tibial tuberosity → inflammation of the patellar ligament
* Can lead to avulsion fractures and excess tibial tuberosity growth
* Treatment – RICE
* Rest – avoid strenuous sports and the pain should go away over weeks or months
* Ice – to prevent pain & swelling
* Compression
* Elevation
42
Name and describe 11 types of bone fractures.
_Types of Bone Fractures_
1. **Spiral**: from twisting stresses, along the length of the bone
2. **Transverse**: straight accross the bone
3. **Oblique**: on an angle
4. **Greenstick**: one side of the shaft is broken and the other side is bent
5. **Fissure**: a crack in the bone
6. **Impacted**: pressure driving bones together
7. **Avulsion**: a fragment of bone tears away from the main bone mass
8. **Displaced**: production of new and abnormal arrangements of bony elements
9. **Ephyseal**: can permenantly halt further longitudinal growth
10. **Compression**: occurs in vertebrae subjected to extreme stress
11. **Comminuted**: shattering; multiple breaks
43
Name the four basic steps involved in bone fracture healing.
**Bone Fracture Healing - Basic Steps**
1. Haematoma – bleeding & bruising
2. Soft callus formation
3. Hard callus formation
4. Remodelling
44
Describe the phases of the gait cycle.
_Phases of the Gait Cycle._
**Stance Phase**
1. **Heel** **strike** – tibialis anterior lowers the forefoot to the ground; gluteus maximus continues deceleration; dorsiflexors eccentrically contract
2. **Loading** **response** – quadriceps accept the weight; triceps surae act to slow dorsiflexion
3. **Midstance** –triceps surae eccentrically contract to control dorsiflexion & maintain momentum; gluteus medius & tensor fascia lata stabilise the pelvis
4. **Terminal Stance** – triceps surae concentrically contract to push the forefoot down to produce push-off, providing propulsive force
5. **Preswing** – flexor hallucis longus and flexor digitorum longus stabilise the forefoot and maximise plantar flexion; rectus femoris & iliopsoas eccentrically contract to decelerate the thigh
**Swing Phase**
1. **Initial** **Swing** - hip flexors (rectus femoris) accelerate the thigh to increase speed; tibialis anterior dorsiflexes the ankle so the foot will clear the ground
2. **Terminal** **Swing** – hamstrings eccentrically contract to decelerate while moving forward; quadriceps contract to extend the leg and position (tibialis anterior) the foot for heel strike
45
Describe 6 types of gait abnormality.
_Types of Gait Abnormality_
1. **Antalgic Gait**
* ****Adoption of a limp to avoid pain in weight-bearing structures (e.g. hip, knee, ankle
* Due to pain
2. **Ataxic Gait**
* ****Drunken’ - unsteady, uncoordinated walk with a wide base of support
* Due to Cerebellar disease
3. **Festinating Gait**
* ****‘Shuffling’ - short, accelerating steps used to move forward
* Due to Parkinson’s disease
4. **Hemiplegic Gait**
* ****Flexion of the hip due to inability to clear the toes from the floor at the ankle
* Due to Weakness on one side e.g. from stroke
5. **Spastic Gait**
* ****Walking with legs held close together and in a stiff manner
* Due to CNS injury
6. **Trendelenberg Gait**
* ****The good hip falls when there is weight on the bad hip; compensation with shoulders
* Due to Hip instability
46
List some of the provisions of the Universal Declaration of the Rights of the Child.
**Universal Declaration of the Rights of the Child.**
1. Rights for all children
2. Children need special protection
3. Entitled to name and nationality at birth
4. Right to health and social security
5. Special attention to handicapped children
6. Child needs care, affection and understanding
7. Children need education
8. Child to be first to receive protection and relief in all circumstances
9. Protection from neglect, cruelty and exploitation
10. Protection from racial, religious or other discrimination
47
List some of the muscles that act at the hip.
48
Describe the 4 components that make up the extracellular matrix.
_Components of the Extracellular Matrix_
1. **Protein Fibers** – collagens, elastin
2. Proteoglycans and glycosaminoglycans (GAGs)
* **Glycasaminoglycans** (hyaluronate)- unbranched polysaccharide units
* **Proteoglycans**: core proteins, e.g. heparan sulphate
* **Proteoglycans bind to GAGs** to form a network surrounding collagen
3. **Adhesion molecules**
* Multiple binding sites to ECM and cells
* **Fibronectin** – ‘glues’ ECM components together (integrins, collagens, GAGs)
* **Laminin** – in the basal lamina; allows the basal lamina to act as a surface for cell attachment
4. **Integrins**
* Transmembrane proteins
* Recognise RGD motif on fibronectin, laminin, collagen etc.
* Bind ECM components extracellularly and the actin cytoskeleton intracellularly
49
Outline the synthesis of collagen.
**Synthesis of Collagen**
1. Single collagen polypeptides (α-chains) are translated by ribosome
2. Lysine and proline side chains are hydroxylated to allow hydrogen bonds to form between chains
3. Three α-chains come together in the endoplasmic reticulum
4. Procollagen is packaged by the golgi apparatus and exported via exocytosis
5. Procollagen is processed by peptidases to form tropocollagen
6. Tropocollagen is packed into a linear array to form a collagen fibril
7. Cross-links between fibrils are formed → collagen fibers
50
Describe 4 of the key collagen disorders.
_Collagen Disorders_
1. **Ehlers- Danlos syndrome**
* ********Mutations in collagen genes (type II) or associated enzymes (lysyl hydroxylase)
* Defective fibril formation
* Joint hypermobility, hernias, ocular fragility
2. **Osteogenesis imperfecta (brittle bone disease)**
* Mutations in collagen genes – usually type I collagen
* Abnormal binding and organisation of collagen
* Bone fractures, deformities, thin skin, ↓ life span, hearing loss
3. **Scurvy**
* Vitamin C deficiency - essential for collagen synthesis
* No hydroxylation → no hydrogen bonding → no cross-linking → instability
4. **Marfan’s syndrome**
* Mutations in fibrillin or elastin genes
* Extension of long bones and thin blood vessel walls
* Long fingers/ toes, vision problems, heart problems
51
List the components that make up bone, including cells, inorganic and organic matter.
_Components of Bone_
1. **Cells**
* Osteoblasts
* Osteocytes
* Osteoclasts
2. **Osteoid** – organic matrix (~30% of compact bone by weight)
* Ground substance – ECF, proteoglycans (chondroitin sulphate & hyaluronic acid)
* Collagen (type I) fibres (~90% of the organic matrix)
3. **Cement**
4. **Inorganic** **salts** (~70% of compact bone by weight)
* Provide hardness and resistance to compression
* Ca2+ and PO43-, in the form of hydroxyapatite – Ca10(PO4)6(OH)2
52
Describe the 3 types of bone.
_Types of Bone_
1. **Woven** **bone** - forms from ossified connective tissue
* Relatively poor mechanical properties, but can be produced quickly
* Useful for fracture repair in short term – replaced by lamellar bone
* Found in inner ear capsule, between sutures of cranial bones, early fracture repair
2. **Fibro-lamellar bone** - found where bone growth is fairly rapid
* e.g. foetal bone development or during peak height velocity growth
* Appearance of a brick wall - bricks = bone; mortar = blood vessels
* Tends to be replaced by stiffer and stronger lamellar bone
3. **Lamellar** **bone** - concentric layers (lamellae) of bone
* Two types of lamellar bone – compact and spongy
53
List some of the functions of free calcium.
_Functions of Free Calcium_
## Footnote
1. Influences **protein** **stability**
2. Acts as a **second messenger**
* *3. Synaptic transmission**
4. **Blood clotting** (as a cofactor)
5. Important in **muscle contraction**
6. Maintenance of **tight junctions** between cells
7. Stimulus-secretion coupling (Ca2+ entry into cells → exocytosis of secretory contents)
54
Describe the effects of parathyroid hormone on bone, GIT and kidneys.
_Effects of Parathyroid Hormone_
↑Ca2+ and ↓PO43- in plasma
1. **Bone**
* Fast efflux of Ca2+ from the labile pool(Ca2+ pumps)
* Bone resorption → ↑Ca2+ and ↑PO43- from the stable pool
2. **GIT**
* Activates Vitamin D3 (kidney)→ ↑ intestinal absorption of Ca2+ and PO43-
3. **Kidney**
* ↑ tubular reabsorption of Ca2+
* ↓ tubular reabsorption of PO43- - prevents Ca2+ precipitation
55
Describe the effects of vitamin D3.
_Effects of Vitamin D3_
↑Ca2+ and ↓PO43- in plasma
* ↑Ca2+ and PO43- absorption from the intestine
* Stimulates formation of calcium binding protein (CaBP), Ca2+-stimulated ATPase and ALP
* PO43- follows Na+ and calcitriol into enterocytes
* ↑RANKL production by osteoblasts → ↑bone resorption
56
Describe the effects of calcitonin.
**Effects of Calcitonin**
↓Ca2+ and ↓PO43- in plasma
* Inhibits osteoclast activity
* Inhibits Ca2+ absorption from the intestine
* Inhibits Ca2+ and PO43- reabsorption from the kidneys
57
Describe the roles of IL-6, M-CSF, RANK-L and OPG in regulation of bone metabolism.
* **Interleukin-6 (IL-6)** - secreted by osteoblasts and osteoclasts
* Indirectly stimulates osteoclast activity & differentiation (by stimulating osteoblasts to produce RANKL)
* **Macrophage** **Colony** **Stimulating** **Factor** (M-CSF/CSF-1) - secreted by osteoblasts and stromal cells
* Stimulates monocyte, macrophage and osteoclast activity and differentiation
* **RANK Ligand (RANKL)** - produced by osteoblasts, bound to osteoblast cell surface
* Stimulates osteoclast differentiation
* **Osteoprotegerin (OPG)** - produced by osteoblasts
* RANK structural analogue that binds RANKL and prevents the action of RANK
* → inhibits osteoclast differentiation
58
List some primary and secondary causes of osteoporosis.
_Primary Osteoporosis_
1. **Post-menopausal** - ↓oestrogen following menopause → ↑IL-6, IL-1, TNF-α → ↑RANKL/OPG ratio → ↑osteoclast maturation and bone resorption → ↑osteoblast activity to compensate
2. **Senile** (age-related) - diminished osteoblastic capacity in elderly individuals
3. **Disuse** - localised to a certain bone or region
_Secondary Osteoporosis_
1. **Endocrine** – hyperparathyroidism, hyper/hypothyroidism, hypogonadism, pituitary tumours, type I Diabetes Mellitus, Addison’s disease
2. **Medications** – anticoagulants, chemotherapy, corticosteroids, anticonvulsants, alcohol
3. **Neoplasia** - multiple myeloma, carcinomatosis
4. **Gastrointestinal** - malnutrition/malabsorption, hepatic insufficiency, vitamin C**/**D deficiencies
5. **Rheumatological** **disease**
6. **Other** - osteogenesis imperfecta, immobilisation, pulmonary disease, anaemia
59
List 7 modifiable and 7 non-modifiable risk factors of osteoporosis.
_Osteoporosis Risk Factors_
**Non-modifiable**
1. Early menopause
2. Personal or family history of fractures
3. Caucasian or Asian race
4. Long femoral hip axis length
5. Advanced age (senile osteoporosis)
6. Female sex
7. Dementia
**Modifiable**
1. Poor health/frailty
2. Smoking & alcohol
3. Diet (especially inadequate calcium & vitamin D intake)
4. Reduced physical activity
5. Heavy caffeine use
6. Medications (glucocorticoids)
7. Diseases (endocrine, rheumatoid arthritis)
60
List some major causes of falls in the elderly.
_Major causes of falls in the elderly_
1. **Osteoporosis**
2. **Lack of physical activity** – poor muscle tone, decreased strength, loss of bone mass and flexibility
3. **Impaired vision**
4. **Medications** – sedatives, antidepressants, anti-psychotic drugs → ↓mental alertness, balance & gait issues
5. **Environmental** **hazards** – mostly tripping over objects on the floor, poor lighting, loose rugs
61
Describe the 3 types of Dementia.
6 causes?
_Types of Dementia_
1. **Static** – a fixed state of dementia; due to a single event (brain injury)
2. **Slowly** **progressive** – worsens over several years; usually due to neurodegenerative disease
1. Alzheimer’s disease
2. Vascular dementia (underlying condition e.g. stroke, ischaemia)
3. Lewy body dementia
4. Frontotemporal lobe degeneration
5. Huntington’s disease
6. Hypothyroidism – but can often be fully reversed with treatment
3. **Rapidly** **progressive** – worsens over weeks to months; caused by the same conditions as slowly progressing
62
List the layers surrounding the spinal cord.
_Layers surrounding the spinal cord = Meninges_
1. Vertebral Bone
2. Epidural Space (fat)
3. **Dura** **Mater** - tough, fibrous outermost layer Dura-arachnoid Interface
4. **Arachnoid** **Mater** - delicate, avascular membrane Subarachnoid Space
5. **Pia** **Mater** – innermost later of flattened cells Spinal Cord – white and grey matter
63
List the extrinsic and intrinsic muscles of the back.
_Extrinsic Back Muscles_
* **Superficial** – trapezius, latissimus dorsi, levator scapulae, rhomboids
* **Intermediate** - erratus posterior superior & inferior
_Intrinsic Back Muscles_
* **Superficial** – splenius cervicis (→cervical vertebrae), splenius capitis (→skull)
* **Intermediate – erector spinae group**
1. Spinalis
2. Longissimus
3. Iliocostalis
* **Deep** - transversospinal group
1. Semispinalis
2. Multifidus
3. Rotatores
64
Contrast dorsal and ventral nerve roots.
_Dorsal root_
* **Contains** → Afferent (sensory) fibres
* **Function** → Receive sensory stimuli from skin, subcutaneous and deep tissues
* **Neuronal** **cell** **bodies** → Located in dorsal root ganglia
_Ventral root_
* **Contains** → Efferent (motor) fibres
* **Function** → Send motor stimuli to skeletal & smooth muscle
* **Neuronal** **cell** **bodies** → Located in ventral grey horns
65
List 6 age-related changes to intervertebral discs.
**Age-related changes to intervertebral discs**
1. Loss of water and increased collagen in the nucleus pulposus
2. Loss of disc height
3. Disc bulge/herniation
4. Compressive stress → compression fractures
5. Formation of osteophytes – osseous outgrowths
6. Increased, more random range of movement
66
List 7 major causes of lower back pain.
_Major causes of lower back pain_
1. **IV** **discs** – degeneration, herniation
2. **Vertebrae** - Spondylolisthesis, Scheuermann’s kyphosis, fractures (may be from osteoporosis), spinal stenosis, infection, tumours, osteomalacia, Paget’s disease
3. **Spinal** **Cord** - epidural abcess, intradural tumours
4. **Joints** - apophyseal osteoarthritis (facet joints), rheumatoid arthritis, ankylosing spondylitis, chondrocalcinosis
5. **Misalignments** – postural, differences in leg length, misaligned pelvis, abnormal foot pronation
6. **Referred** **Pain** – from pelvic or abdominal organs
7. **Psychogenic**/**Neurogenic** – stress, depression
67
Contrast fast and slow pain.
68
List 9 effects of morphine.
_Effects of Morphine_
1. **Analgesia** – pain reduction
2. **Euphoria** – sense of well-being
3. **Dysphoria** – unpleasant mood
4. **Sedation**
5. Respiratory depression
6. Pupil constriction
7. ↓Gastrointestinal motility – can cause nausea/emesis
8. Stimulation of **histamine** release – can cause itching
9. **Physical dependence, withdrawal**
69
List 3 major therapeutic effects of NSAIDs.
_Major therapeutic effects of NSAIDs_
1. **Anti-inflammatory** - inhibition of COX2 →↓production of prostaglandins (PGs)
2. **Analgesic** - ↓PGs →↓sensitisation of pain receptors to inflammatory mediators (nociceptive pain only)
3. **Antipyretic** - ↓PGE2 → resetting of hypothalamic set point
70
Describe the WHO analgesic ladder.
_WHO Analgesic Ladder_
* **Mild** **Pain** → Non-opioid ± adjuvant
* **Moderate** **Pain** or not controlled by #1 → Weak opioid ± non-opioid ± adjuvant
* **Severe** **Pain** or not controlled by #1/2 → Strong opioid ± non-opioid ± adjuvant
71
List 7 types of medical certificates.
**Types of Medical Certificates**
1. Sickness certificates
2. Insurance certificates
3. Registration of births and deaths
4. Burials and cremations
5. Transplantation procedures
6. Post-mortem and anatomical investigations
7. Compulsory detention under mental health legislation
72
Give 6 points of general guidelines regarding the writing of medical certificates.
**Writing Medical Certificates**
1. Should be legible and written on formal letterhead (or at least include doctor’s full name and address)
* Include date of examination, date of expected recovery and degree of incapacitation
* If requested, indicate whether there should be altered duties when the patient returns to work
2. No abbreviations or medical jargon
3. Should be based on fact, observations and opinions of the doctor, not those of the patient
4. No back-dating or post-dating- the date on certificate should be the date of the examination
5. Must respect the patient’s confidentiality – can state that they can’t work due to a ‘medical condition’ – but should advise the patient if there is insufficient information on the certificate
6. In the case of injury – the certificate should not definitively state that the injury was caused by the patient’s description of events, but may state that the injury is consistent with the circumstances described
73
List the carpal bones.
_Some Lovers Try Positions That They Can’t Handle_
* **Proximal Row**
* Scaphoid
* Lunate
* Triquetrum
* Pisiform
* **Distal row**
* Trapezium
* Trapezoid
* Capitate
* Hamate
74
List the muscles of the rotator cuff.
**Rotator Cuff Muslces = SITS**
1. Supraspinatus
2. Infraspinatus
3. Teres minor
4. Subscapularis
75
List some landmarks indicating the dermatomes of the upper limb.
**Dermatomes - Upper Limb - Landmarks**
* C3 – upper neck
* C4 – supraclavicular fossa
* C5 – anterior to coracoid process
* C6 – lateral arm → thumb
* C7 – posterior arm → index & middle fingers
* C8 – medial arm → ring & little fingers
* T1 – upper axilla
76
Describe 8 types of open wound.
_Types of Open Wounds_
1. **Incision**: a cut made with a knife/other sharp instrument
2. **Laceration**: a torn or jagged wound caused by blunt trauma (more of a tear than a cut)
3. **Abrasion**: removal of superficial layers of skin/mucous membrane
4. **Puncture** **wound**: a wound where the opening is relatively small compared to the depth
5. **Penetrating** **wound**: disruption of the body surface that extends into underlying tissue or a body cavity
6. **Gunshot** **wound**: caused by a bullet or projectile (?exit wounds)
7. **Avulsion**: tearing or forceful separation (incompletely removed)
8. **Amputation**: severing of a limb, part of a limb, a breast or other projecting part
77
Describe three general phases of wound healing.
**Wound Healing**
1. Inflammation (early/acute and late/chronic)
2. Granulation tissue formation and re-epithelialisation
3. Wound contraction, ECM deposition and remodelling
78
Outline the actions of the chemical mediators involved in wound healing.
79
List some long term effects of small and large alcohol consumption.
80
Outline the embryological origins of the central nervous system structure.
81
List the names of the cranial nerves, the location of their cell bodies and the cranial foramina they pass through.
**Ooh, Ooh, Ooh, to touch and feel very good velvet. Such heaven!**
* O: olfactory nerve (CN I)
* O: optic nerve (CN II)
* O: oculomotor nerve (CN III)
* T: trochlear nerve (CN IV)
* T: trigeminal nerve(CN V)
* A: abducens nerve (CN VI)
* F: facial nerve (CN VII)
* A: auditory (or vestibulocochlear) nerve (CN VIII)
* G: glossopharyngeal nerve (CN IX)
* V: vagus nerve (CN X)
* S: spinal accessory nerve (CN XI)
* H: hypoglossal nerve (CN XII)
82
List the functions of each cranial nerve.
Some say marry money but my brother says big boobs matter more
* S: sensory (olfactory nerve - CN I)
* S: sensory (optic nerve - CN II)
* M: motor (oculomotor nerve - CN III)
* M: motor (trochlear nerve - CN IV)
* B: both (trigeminal nerve - CN V)
* M: motor (abducens nerve - CN VI)
* B: both (facial nerve - CN VII)
* S: sensory (vestibulocochlear nerve - CN VIII)
* B: both (glossopharyngeal nerve CN IX)
* B: both (vagus nerve - CN X)
* M: motor (spinal accessory nerve - CN XI)
* M: motor (hypoglossal nerve - CN XII)
83
List 5 major functional areas of the frontal cortex.
_Frontal Cortex - Functional Areas_
1. **Primary motor cortex (pre-central gyrus)**
* Voluntary movement of skeletal muscle
* Motor homunculus
2. **Premotor & supplementary motor areas**
* Movement planning and posture
3. **Broca’s area (motor speech area)**
* Inferior frontal gyrus of dominant hemisphere (usually left)
* Formation of words
4. **Prefrontal cortex**
* Thought, problem solving, personality
5. **Frontal eye field**
* Voluntary conjugate deviation of eyes (scanning the visual field)
84
List 2 major functional areas of the parietal cortex.
_Parietal Cortex - Functional Areas_
1. **Primary somatosensory cortex (post-central gyrus)**
* Touch, vibration, pressure, pain, temperature, proprioception (awareness, location intensity)
* Sensory homunculus
2. **Somatosensory association area**
* Processing complex sensory information to accomplish purposeful movement
* Connections with premotor and sensory areas
85
List 3 major functional areas of the temporal cortex.
_Temporal Cortex - Functional Areas_
1. **Primary, secondary and tertiary auditory areas**
* Receive information from medial geniculate nucleus of thalamus
2. **Wernicke’s area (sensory speech area)**
* Receives information from primary & visual areas
* Understanding & formulating language – connected to Broca’s area via the arcuate fasciculus
3. **Olfactory Cortex**
86
List three functions of the basal ganglia.
**Basal Ganglia - Functions**
1. Inhibition of muscle tone
2. Coordination of slow, sustained movements
3. Suppression of unwanted/inappropriate patterns of movement
87
List three functional parts of the medulla oblongata.
_Medulla Oblongata - Functional Areas_
1. **Cardiovascular centre**
* Cardiac and vasomotor systems
* Adjust heart rate, contractility and blood flow
2. **Respiratory centre**
* Regulated by apneustic & pneumotaxic centres of pons
3. Cell bodies of **cranial** **nerves** VIII, IX, XI, XII
88
List 4 functional parts of the midbrain.
_Midbrain - Functional Areas_
1. Cell bodies of **cranial** **nerves** III and IV - eye movement
2. 4 colliculi
* **Superior** **colliculus** – visual reflexes
* **Inferior** **colliculus** – auditory reflexes
3. **Substantia** **nigra** – inhibits motor, secretes **dopamine**
4. **Red** **nucleus** – involuntary control of background muscle control & limb position
89
List 3 functional parts of the medulla oblongata.
_Medulla Oblongata - Functional Areas_
1. **Cardiovascular centre**
* Cardiac and vasomotor systems
* Adjust heart rate, contractility and blood flow
2. **Respiratory centre**
* Regulated by apneustic & pneumotaxic centres of pons
3. Cell bodies of **cranial** **nerves** VIII, IX, XI, XII
90
List 3 functional areas of the cerebellum.
_Cerebellum - Functional Areas_
1. **Vestibulocerebellum** – balance, eye and head coordination
2. **Spinocerebellum** – limb movement, regulation of muscle tone
3. **Cerebrocerebellum** – initiation & execution of preprogrammed rapid events; coordination of fine movement
91
List 5 major functional parts of the limbic system.
_Limbic System - Functional Areas_
1. **Hippocampus** – long-term memory
2. **Amygdala** – learned emotional responses (fear), recognition of emotions in others, unconscious emotion
3. **Fornix** – axons from the hippocampus to the mamillary bodies
4. **Mamillary** **bodies** – processing of recognition memory
5. **Cingulate** **gyrus** – emotion formation and processing, memory
92
List the major parts of the spinal cord descending tract.
_Spinal Cord - Descending Tract_
1. **Corticospinal (pyramidal) tract** – provides conscious control of skeletal muscle
* Corticobulbar tract – eye, jaw, face and some of the neck
* Lateral – precise movement control
* Anterior – gross motor control
2. **Extrapyramidal** **tract** – from the pons, medulla oblongata, midbrain
* Vestibulospinal tract – subconscious balance, tonicity of muscles
* Tectospinal tract – subconscious/reflex responses to auditory & visual stimuli
* Reticulospinal tract – prevents unwanted reflexes o Rubrospinal tract – tone, movement
93
List the major parts of the spinal cord ascending tract.
_Spinal Cord - Ascending Tract_
1. **Dorsal column** – proprioception, fine touch, pressure, vibration
* Fasciculus gracilis – innervates the lower part of the body
* Fasciculus cuneatus – innervates the upper part of the body
2. **Anterolateral system (ALS)**
* Spinothalamic tract
* Lateral part – pain, temperature
* Anterior part – crude touch, pressure
* Spinoreticular tract, spinohypothalamic tract and spinomesencephalic tract
3. **Spinocerebellar** **tracts** – proprioceptive information from limbs to cerebellum
* Dorsal
* Ventral
94
Outline the 3 types of proprioceptors.
_Types of Proprioceptors_
1. **Muscle spindles (intrafusal fibres)** – in fleshy part of muscle, parallel to extrafusal fibers
* Primary sensory endings – sensitive to length, change in length and velocity of change
* Secondary sensory endings – sensitive to length only
2. **Golgi tendon organs** – in junction between muscle and tendon, perpendicular to extrafusal fibers
3. **Joint** **receptors** – in joint capsule, send information about joint position
95
Give some information regarding three major types of aphasia.
**Aphasia** = a language disorder that is caused by an injury to specific parts of the brain related to language.
**3 Kinds of Aphasia:**
1. Broca's aphasia
2. Wernicke's aphasia
3. Global aphasia.
All three interfere with your ability to speak and understand language.
96
Contrast upper and lower motor neuron lesions in terms of:
* Muscle Strength
* Muscle Tone
* Reflex strength
* Wasting
* Causes
97
List 15 modifiable and 5 non-modifiable risk factors for stroke.
**Non-Modifiable Risk Factors for Stroke**
1. ↑Age
2. Male gender
3. Ethnicity (especially African descent)
4. Family history of stroke
5. Previous stroke or transient ischaemic attack
**Modifiable Risk Factors for Stroke**
1. Hypertension
2. Atrial fibrillation
3. Diabetes mellitus
4. Atherosclerosis
5. Venous thrombosis
6. Vasculitis
7. Haematological disorders (hypercoagulability, polycythaemia, thrombocytosis, sickle cell)
8. Hyperlipidaemia
9. Atrial fibrillation
10. Smoking
11. Illicit drug use (especially heroine, cocaine, amphetamines)
12. Obesity
13. Physical inactivity
14. Excessive alcohol intake
15. Hormone replacement therapy
98
Outline the 2 types of stroke and their causes.
_Types of Stroke_
1. **Ischaemic stroke** (~85%) - occlusion of a blood vessel to the brain, generally due to embolus or thrombus
2. **Haemorrhagic stroke** (~15%) - ruptured vessel in brain tissue or subarachnoid space
* **Subarachnoid** **haemorrhage** – intracranial bleeding in the subarachnoid space
* Due to aneurysm, trauma, rupture of an arteriovenous malformation, conversion of ischaemic stroke
* **Intracerebral** **haemorrhage** – haemorrhage in the brain parenchyma, which may expand into the ventricles or subarachnoid space
* Due to hypertension, amyloid angiopathy, coagulopathy, AVM rupture, recreational drug use, trauma
99
List some general signs/symptoms of stroke.
_Signs/Symptoms of Stroke_
1. Sudden onset motor/sensory loss
2. Dysarthria or aphasia
3. Visual loss in one eye or hemifield in both eyes
4. Ataxia/dysmetria of the limbs
5. Altered level of consciousness
6. Sudden severe headache
100
Give the names and functions of the water-soluble vitamins.
* B1 = Thiamine
* B2 = Riboflavin
* B3 = Niacin/Niacinamide
* B5 = Pantothenic acid
* B6 = Pyridoxine/Pyridoxamine
* B7 = Biotin
* B9 = Folic acid/Folinic acid
* B12 = Cyanocobalamin/Hydroxycomalamin/Methylcobalamin
* C = Ascorbic acid
101
Outline the treatment of ischaemic and haemorrhagic Stroke.
_Treatment of Stroke_
**Ischaemic Stroke**
1. **Thrombolytics**– tissue plasminogen activator (tPA) up to three hours after onset of stroke
* Contraindicated in the case of previous haemorrhagic stroke, seizure, tendency to bleed, recent major surgery, recent head injury, heart infection, use of warfarin
2. **Anticoagulants** – for ischaemic stroke (after CT has been used to exclude haemorrhagic stroke)
3. **Surgery** – removal of atheromas or clots (endarerectomy)
4. **Rehabilitation** and **lifestyle** **modification** to reduce reaoccurence
**Haemorrhagic** **Stroke**
1. Helping the **blood** to **clot** - vitamin K, transfusion of platelets, synthetic clotting factors
2. **Mild sedatives** to control agitation
3. Prophylactic prevention of vasospasm with **calcium** **channel** **blockers**
4. May need **surgery** to remove intracerebral haematoma
