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1
Q

What are mesenchymal cells?

A

Cells of connective tissues

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2
Q
What are the names of the tumours arising from the following ells?
Epithelial cells
Mesenchymal cells
Haematopoietic cells
Neural cells
A

Carcinomas
Sarcomas
Leukaemias (from bone marrow cells); lymphomas
Neuroblastomas; gliomas

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3
Q

What are the 3 components of a tissue?

A

Cells, extracellular matrix and fluid

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4
Q

What are the flattened sacs of the ER known as?

A

Cisternae

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5
Q

Give the structure and function of microtubules. Indicate relative size.

A

Polymers of a and b tubulin heterodimers. Involved in cells shape and acts as tracks for organelles and other cytoplasmic components of the cell to follow. They also form the mitotic spindle. -20nm thickness - thickest polymers in the cytoskeleton

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6
Q

Give the structure of cilia and flagella

A

9 microtubule doublets and 2central microtubules (9+2 arrangement). ATP dependent motor proteins distort organelles to produce movement.

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7
Q

Give the structure and function of intermediate filaments

A

Polymers of filamentous proteins. IFs give mechanical strength to cells. About 15nm thick.

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8
Q

What are nuclear lamins?

A

Intermediate filaments which form a network on the internal surface of the nuclear envelope called the nuclear lamina.

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9
Q

Give the structure and function of microfilaments.

A

Polymers of actin. Associate with adhesion belts in epithelia; involved in cell shape and movement. 5-9nm thick.

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10
Q

What are the types of shape and layering present in epithelia.

A

Squamous, cuboidal and columnar. Simple and stratified layering.

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11
Q

What is a keratinising stratified epithelium?

A

Cells of the upper layer of the epithelium are “dry” because they have died and hardened. Their nuclei are not visible.

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12
Q

Junctions separate epithelial membranes into 2 biochemically and functionally distinct domains, which are…

A

The apical domain and basolateral domain.

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13
Q

What are maculae and zonulae?

A

Maculae are junctions arranged as discrete spots. Zonulae are junctions arranged as continuous belts.

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14
Q

Describe briefly the apical junctional complex of simple epithelia.

A

Typically, there is a tight junction nearest the apex with an adherens junction just below it. Desmosomes (spot adhering junctions) are scattered throughout the lateral membrane.

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15
Q

How do tight junctions seal the paracellular pathway? What are the implications of this?

A

Proteins on adjacent membranes closely interact to form sealing strands.
This means concentration differences across cell layers can be maintained and the cells control the passage of solutes crossing the cell layer.

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16
Q

Define exocrine and endocrine secretory functions?

A
Exocrine = into a duct or lumen
Endocrine = into blood stream
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17
Q

What are the 3 main layers of the skin, what type of epithelium is this and which is the keratinising layer?

A

The epidermis, dermis and hypodermis. Stratified squamous epithelium. The epithelium is keratinising.

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18
Q

Describe the function of desmosomes and hemidesmosomes.

A

Desmosomes link cells to each other to give mechanical stability to tissues including epithelia and cardiac tissue. Hemidesmosomes link the cells to the ECM.

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19
Q

How are epithelial cells on the surface of villi in the lumen of the small intestine replaced?

A

Stem cells in the crypts of Lieberkühn produce new epithelial cells to replace the cells lost at the villus tip, which then migrate upwards.

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20
Q

Describe the cell turnover of the epidermis.

A

Surface cells are constantly being lost, but are replaced by new cells being formed in the basal layer which migrates up which undergoing differentiation leading them to flatten and keratinise. Each layer replaces the one above as the layers are lost from the surface.

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21
Q

What is the ECM?

A

Complex network of macromolecules deposited by cells filling the space between them.

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22
Q

What are the main components of the ECM?

A

Collagens, glycoproteins and proteoglycans.

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23
Q

Describe the structure of a collagen molecule.

A

Triple helical structure formed of 3 a-chains. Every third position must be occupied by glycine, as there is no room near the helical axis for the side chain of any other residue.

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24
Q

Describe the biosynthesis and assembly of collagen.

A

Procollagen has non-collagenous domains (propeptides) at the N and C terminals which are removed after secretion by extracellular peptidases. The collagen helices associate laterally to from collagen fibrils, which associate laterally in turn to form collagen fibers.

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25
Q

Describe simply the structure of elastic fibers

A

Core made of the protein elastin and microfibrils rich in the protein fibrillin.

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26
Q

What are basement membranes / basal lamina?

A

Flexible, thin sheets of highly specialised ECM underlying epithelial sheets and tissues.

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27
Q

What type of collagen assembles into sheet-like networks and is an integral part of basal lamina? What is the other major component?

A

Collagen type IV. Laminins (these are glycoproteins).

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28
Q

Describe the structure of laminins.

A

Three chains: an alpha, a beta and a gamma chain. Form a cross-shaped molecule. They are very large: each chain can be up to 400kDa.

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29
Q

Mutations in which component of the basal lamina are associated with muscular dystrophy? What are the symptoms of DMD?

A

Laminins.
Hypotonia (abnormally decreased muscle tension), generalised weakness, deformities of the joints. All evident from birth.

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30
Q

What are fibronectins?

A

A family of closely related glycoproteins found in the ECM.

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31
Q

How is a mechanical continuum between the ECM and actin cytoskeleton produced?

A

Collagen fibers of the ECM associate with fibronectin. Fibronectin interacts with integrin receptors at the cell surface. These span the plasma membrane and connect the ECM to actin filaments via an adaptor protein.

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32
Q

What is a proteoglycan?

A

A protein to which one or more glycosaminoglycan (GAG) chains are covalently attached.

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33
Q

Describe the structure of glycosaminoglycans (GAGs)

A

Long, unbranched sugars consisting of repeating disaccharides. They occupy a huge volume relative to their mass.

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34
Q

What is the function of proteoglycans?

A

Their GAG chains form hydrated gels, making tissues resistant to compression.

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35
Q

What is hyaluronan and where is it synthesised?

A

Hyaluronan is a unique proteoglycan consisting of simply a carbohydrate chain. It is synthesised at the cell surface (NOT the ER/Golgi)

36
Q

What makes aggrecan suitable to resist compressive forces and hence aid cartilage function?

A

Aggrecan’s GAGs are highly sulphated, which are negatively charged. This attracts cations, such as Na+, which are osmotically active so large quantities of water are retained. Under compressive load, the water is given up.

37
Q

Explain the cause of osteoarthritis.

A

Aggrecan is cleaved by aggrecanase and metalloproteinase. Aggrecan fragments lost to synovial fluid. Excessive ECM degradation: the cushioning properties of cartilage over the end of bones is lost.

38
Q

Define osmolarity

A

A measure of the concentration of all solute particles in a solution.

39
Q

What is the osmolarity of a 1mmol/L solution of CaCl2?

A

3mmol/L as each calcium chloride dissociates into 3 ions each of concentration 1mmol/L

40
Q

What is colloid osmotic pressure (COP)?

A

Inward acting osmotic pressure due to the concentration of protein being greater in capillaries than outside.

41
Q

Define oedema. Suggest a cause.

A

Swelling of a tissue because of excess interstitial fluid. When the leakage of plasma into the interstitial space exceeds the capacity of the lymphatics to collect and return it to circulation.

42
Q

Where is lymph fluid returned to circulation?

A

50% in lymphatic ducts in subclavian region; 50% from lymph nodes.

43
Q

Give 3 types of oedema and their causes.

A

INFLAMMATORY OEDEMA: local blood vessels become leaky.
HYDROSTATIC OEDEMA: high blood pressure increases hydrostatic pressure in vessels.
CANCER SURVIVOR: lymph nodes may be removed as part of cancer treatment.

44
Q

What 2 types of muscle are in an antagonistic pair?

A

A flexor and an extensor

45
Q

Define isometric contraction

A

A contraction in which the muscle doesn’t change length (for example when carrying a plastic bag)

46
Q

What are the two types of isotonic contraction?

A

Concentric contraction (shortening) and an eccentric contraction (lengthening).

47
Q

Recall how calcium ions are released from the SR in skeletal muscles

A

An action potential propagates along the sarcolemma. Depolarisation causes a conformational change in dihydropyridine receptors (DHPR). This causes ryanodine receptors (RyR) to open releasing Ca2+ from the SR.

48
Q

What is titin?

A

A large spring-like filament anchoring myosin to the Z-line.

49
Q

What causes the myosin head to pivot (power stroke) one troponin has exposed the myosin binding site on actin?

A

The discharge of ADP.

50
Q

How does the sliding filament theory apply to isometric contraction?

A

Muscle tension = force exerted by the load. There is no shortening but there is still ATP expenditure recharging the myosin heads.

51
Q

Recall how calcium ions from the SR are released in cardiac muscle (E-C coupling).

A

Depolarisation of the sarcolemma causes voltage gates calcium ion channels (VGCCs) to open. Calcium ions bind to the ryanodine receptors (RyRs) causing calcium induced calcium release (CICR). The released calcium binds to troponin, causing contraction.

52
Q

Recall excitation-contraction (E-C) coupling in smooth muscle.

A

Depolarisation opens VGCCs. A protein, calmodulin, binds to calcium ions to form Ca2+-CaM. This complex activates myosin light chain kinase (MLCK). MLCK phosphorylates myosin light chains which cause contraction.

53
Q

Name the 4 hemispheres of the brain and indicate their positioning.

A

Frontal lobe (front); occipital lobe (back); parietal and temporal lobes (middle).

54
Q

List the 3 components of the brainstem in descending order

A

Midbrain, pons, medulla.

55
Q

What is the cerebellum

A

A hindbrain structure attached to the brainstem with important roles in motor-coordination, balance and posture.

56
Q

Describe the 4 types of morphology of neurones

A

Unipolar: 1 axonal projection
Pseudo-unipolar: Single axonal projection that divides into 2
Bipolar: 2 projections from the cell body
Multipolar: Numerous projections from the cell body

57
Q

How many axons do neurones have?

A

Regardless of how many projections a cell body (soma) has, only ONE is an axon, the rest are categorised as dendrites.

58
Q

Which direction do action potentials travel down an axon?

A

From the soma to the axon hillock.

59
Q

What are dendrites?

A

Soma projections NOT covered in myelin which receive signals from other neurons.

60
Q

What are the most abundant cells in the CNS? What are the functions of this cell type?

A

Astrocytes.

Structure, cell repair, neurotransmitter release and uptake.

61
Q

Describe two differences between oligodendrocytes and Schwann cells.

A

Oligodendrocytes found in CNS and myelinate many axons. Schwann cells found in PNS and myelinate one axons segment only.

62
Q

What do ependymal cells do?

A

Regulate production and movement of cerebrospinal fluid (CSF).

63
Q

Describe saltatory conduction

A

AP spreads along the axon by cable transmission since the myelin prevents AP spreading as it has a high resistance and low capacitance. The AP ‘jumps’ between nodes of Ranvier.

64
Q

Describe how an action potential crosses a synapse

A

AP causes VGCCs to open –> influx of calcium ions. These bind to vesicles containing neurotransmitter (NT) to fuse with the membrane of the presynaptic axon terminal, releasing the NT into the synaptic cleft to diffuse across to the postsynaptic membrane and bind to receptors, causing an AP. The NT then are recycled.

65
Q

Give an example of endocrine signalling.

A

Glucagon released from alpha cells in pancreas due to hypoglycaemia –> causes gluconeogenesis and glycogenolysis in distant cells.

66
Q

Give an example of paracrine signalling.

A

Insulin released from beta cells as a response to hyperglycaemia acts on adjacent alpha cells to inhibit glucagon secretion.

67
Q

Give an example of signalling by membrane-attached proteins.

A

Hep C blood-borne virus detected by APC and presented on MHC Class II to T-lymphocytes, which engages via TCR.

68
Q

Give an example of autocrine signalling.

A

Activated TCR causes secretion of IL-2 - which binds to IL-2 receptors on same cell. (IL = interleukin).

69
Q

Describe how an ionotropic receptor works.

A

Ligand binds to receptor which opens a pore by a conformational change in shape allowing the movement of ions.

70
Q

Give an example of an ionotropic receptor.

A

Nicotine acetylcholine receptor on skeletal muscle. The ligand is ACh.

71
Q

Explain how an enzyme-linked receptor works.

A

Ligand binds to receptors –> receptor clustering. Clustering activates enzyme activity within cytoplasmic domain. Enzymes phosphorylate the receptor. This causes signal proteins to bind to the cytoplasmic domain –> these recruit other signal proteins –> signal generated within cell.

72
Q

How does a G-protein coupled receptor work?

A

Ligand binds to receptor. Conformational change allowing G protein heterodimer to bind. Bound GDP exchanged for GTP. Dissociates into 2 active components (alpha and beta/gamma). Alpha subunit binds to target. GTPase dephosphorylates GTP. Alpha dissociates and associates with beta/gamma subunit becoming inactive again. Receptor active until ligand unbinds.

73
Q

What are the 2 types of intracellular receptors.

A

Type I = cytoplasmic

Type II = nuclear.

74
Q

What are the components of a pilosebaceous unit?

A

Hair follicle, hair shaft, erector pili muscle, sebaceous gland (secretes sebum).

75
Q

What are the 3 type of hair?

A

Lanugo hair (premature babies), vellus (body), terminal (armpit, pubic, scalp, face (thick pigmented hair)).

76
Q

Describe the hair cycle.

A

ANAGEN –> growth phase. 85% of hair at this stage. Energy intensive.
CATAGEN –> cell division stops and slows.
TELOGEN –> hair is shed actively, next anagen phase begins.

77
Q

What is telogen effluvium?

A

A condition where hairs become synchronous again - leading to phases of hair loss and regrowth.

78
Q

Give the layers of the epidermis, from superficial to deep.

A

Stratum corneum, stratum granulosum, stratum spinosum, stratum basale.

79
Q

Is the pH of intracellular and extracellular fluid the same?

A

No, the pH of intracellular fluid is typically 7.1, compared to 7.4 for the interstitial fluid and blood plasma.

80
Q

What is the hyponychium?

A

The thickened epidermis which underlies the free margin of the nail.

81
Q

What is the nail matrix?

A

A region of dividing cells which mature, keratinise and move forward to from the nail plate.

82
Q

What are the proportions of the main fluid compartments?

A

55% intracellular. 36% interstitial. 7% plasma. 2% transcellular.

83
Q

Define non-decremental spread.

A

A defining feature of an action potential: the amplitude remains constant as it travels along the axon.

84
Q

What does the drug vinblastine do?

A

Prevents mitosis from proceeding to anaphase by preventing the formation of microtubules.

85
Q

Briefly describe the roles of ADP and ATP in muscle contraction.

A

ADP = myosin head pivots
ATP binds = releases myosin head from actin
ATP hydrolysis = energy to “recharge”

86
Q

What are the main components of the ECM?

A

Collagens, proteoglycans, multi-adhesive glycoproteins, basement membrane.