Module 1 Structure, function & defence

Question 1

Define the term pharmacodynamics

Answer 1

A drug’s mechanism of action

Question 2

Name the four broad structural types of receptors.

Answer 2

Ligand-gated ion channel, G protein coupled (or 7 transmembrane), tyrosine kinase and cytoplasmic/nuclear.

Question 3

What are the two broad subtypes of receptors for acetylcholine and their different topology

Answer 3

Nicotinic - Ion channel
Muscarinic 7TD receptor with intra and extracellular domains

Question 4

By what characteristics can drugs be classified by?

Answer 4

therapeutic use, mode of action, chemical structure

Question 5

Name two diseases that stem from mutations to one amino acid and how they come about.

Answer 5

Cystic Fibrosis - CTFR ion channel structure is changed which controls Na and Cl movement causing excess mucous to gather in the airways
Sickle Cell disease - Point mutation changes the shape of the erythrocytes

Question 6

What is desensitization and tolerance?

Answer 6

Prolonged treatment can reduce the efficacy of a drug due to receptor desensitisation and can eventually lead to total tolerance.

Question 7

Describe Y linked inheritance and give an example.

Answer 7

Male only inheritance due to only males having X Y chromosomes; webbing of the 2nd and 3rd toes.

Question 8

Are male or females affected predominantly by X linked recessive? Give an example of a X linked recessive disease.

Answer 8

Males are, as they only require 1 copy of the gene to express the phenotype. Haemophilia - defective factor VIII gene involved in clotting

Question 9

Describe Mendelian autosomal dominant, with an example.

Answer 9

Disease is expressed with heterozygous and homozygous patients, for example familial hypocholesteraemia - defective LDL receptor gene on chromosome 19.

Question 10

Describe Mendelian autosomal recessive, with an example.

Answer 10

Require two copies of the defective gene to express the condition, for example cystic fibrosis - CPTR gene on C7. Can be a carrier for autosomal recessive conditions

Question 11

Describe mitochondrial inheritance

Answer 11

Circular DNA that is solely maternal - paternal mitochondria excluded during fertilisation. Conditions such as neuropathy. Can be passed on to male and female offspring but only females can pass on the condition.

Question 12

Inbreeding/consanguinity causes ….., for example……

Answer 12

A higher rate of genetic defects, such as ataxia telangiectasia - coordination issues with movement and speech, enlarged vessels in the eye and an increase in alpha fetoprotein in the blood

Question 13

What causes down syndrome?

Answer 13

An extra Chromosome 21.

Question 14

Define Autocrine, Paracrine, Endocrine, Neurocrine and juxtracrine, with examples.

Answer 14

Autocrine signalling acts on the signalling cell itself - IL-4 in monocytes.
Paracrine signalling acts on nearby cells - Thromboxin from platelets to further clotting cells.
Endocrine signalling uses the circulatory system - hormones.
Neurocrine is nerve signalling.
Juxtacrine is physical contact, such as leukocytes using adhesion molecules on EC.

Question 15

What are the four basic tissue types in the body, and give an example of how they are arranged in tissues.

Answer 15

Connective tissue, epithelial tissue, muscle tissue, and nervous tissue. E.g. GI Tract layers involves epithelium around the lumen, multiple layers of differing connective tissue, and muscle; all arranged in a tubular formation.

Question 16

Name the 3 simple forms of epithelia, their structure (nuclei included) and its function. What does simple mean in this sense?

Answer 16

Simple means monolayer structure.

Squamous - Flattened nuclei. Facilitates passive diffusion of gases or fluids. Large protective sheets (mesothelium) lining the body cavities.

Cuboidal - Central nuclei. Usually found lining small ducts and tubules. May have excretory or absorptive functions.

Columnar - Basal stretched nuclei. Most frequently associated with absorption and secretion. May have microvilli on apical surface for increased surface area. Stratified columnar epithelium: rarer several-layered variant e.g. in urethra, anus

Question 17

What is meant by pseudostratified columnar ciliated and where is it exclusively found?

Answer 17

Variant of simple columnar found almost exclusively in the respiratory tract, sometimes referred to as respiratory epithelium.
1 layer appearing as multiple layers; all are attached to the basement membrane.

Question 18

Describe Stratified squamous keratinizing and non-keratinizing epithelium, and why its structure fits its function.

Answer 18

Non-keratinizing - Lots of cell layers: cuboidal in shape near basement membrane, squamous at surface.
Protective function: well adapted to withstand stress and mechanical abrasion
Found at openings to the outside world.

Keratinizing - Adapted to withstand mechanical and chemical damage as well as water loss – epidermis of skin. Keratin: intermediate filament that builds up in the cells

Question 19

What is urothelium?

Answer 19

Only found in ureter and urinary bladder
Adapted to withstand stretch of bladder wall and the toxicity of urine
Umbrella cells: surface cells that can stretch extensively

Question 20

Name the 5 functions the basement membrane can have

Answer 20

Adhesion
Partition
Barrier/permeability
Anchorage for cell organisation
Controlling growth and differentiation

Question 21

What is the composition of the basement membrane?

Answer 21

Composed mainly of type IV collagen, glycoproteins (laminin secreted by epithelial cells, fibronectin from fibroblasts) and glycosaminoglycans (GAGs)

Question 22

What are the key structural components on the cytoskeleton?

Answer 22

Microfilaments: thin strands of the protein actin that determine the shape of the cell membrane e.g. microvilli

Intermediate filaments: thicker strands of protein that provide mechanical strength e.g. keratin in hair

Microtubules: much larger, determine the movement of cell organelles and intracellular vesicles
Made of tubulin
Grow from centrosome and extend to cell periphery, form mitotic spindle for cell division
Form the core of cilia

Question 23

What are the four cell cell junctions?

Answer 23

Tight junctions
Membranes of adjacent cells are sealed together at points to prevent transport of substances between the cells.

Intermediate junctions (adhering junctions)
Connect actin microfilaments in cytoskeletons of adjacent cells to help maintain integrity of epithelium

Desmosomes
Connect intermediate filaments (e.g. keratin) of adjacent cells to maintain integrity of epithelium.
Hemidesmosomes attach to basement membrane

Gap junctions
Communication between adjacent cells e.g. passage of ions, small molecules

Question 24

How does the structure of Exocrine glands differ to Endocrine?

Answer 24

Exocrine glands: hollow duct forms to the epithelial layer, allowing release of secretions e.g. sweat glands, liver

Endocrine glands: connection to epithelium lost, blood vessels form around the secretory portion to allow for release of secretions e.g. pancreatic islets

Question 25

Exocrine secretion happens in 3 main ways? List them

Answer 25

Merocrine (eccrine): cell vesicles release product via exocytosis e.g. sweat glands Apocrine: vesicles bud off cell with product Holocrine: entire cell ruptures e.g. sebaceous glands

Question 26

Name 2 autoimmune conditions caused by cell junction defects.

Answer 26

Pemphigus vulgaris: antibodies destroy desmosomes, leading to blisters affecting skin and mucous membranes (e.g. mouth) Bullous pemphigoid: antibodies attack hemidesmosomes, leading to raised skin rash and large fluid-filled blisters where epidermis and dermis have separated

Question 27

Connective tissue can have 7 functions. List them?

Answer 27

Binding, packing and support Skeletal framework Protection Insulation Transportation / nourishment Immunological defence Repair (scar tissue)

Question 28

Name the four types of connective tissue cells, and their common name where necessary.

Answer 28

Fibroblasts: primary cell types producing ECM in connective tissue Adipocytes: storage and metabolism of fat, protecting internal organs Chondroblasts and chondrocytes (cartilage) Osteoblasts, osteocytes, osteoclasts (bone)

Question 29

What are Ehlers Danlos syndromes?

Answer 29

Reduced tensile strength from collagen disorders causes tissue laxity, joint hyper mobility and susceptibility to injury

Question 30

There are 3 main types of ordinary connective tissue. Name them and describe their structure/function.

Answer 30

Loose, areolar - Widely distributed below epithelia Forms the lamina propria of a mucosa Surrounds capillaries Dense irregular (fibrous) - Found in dermis, submucosa of digestive tract, fibrous capsules surrounding organs etc. Predominantly collagen fibres, densely packed and irregularly arranged Dense regular (fibrous) - Predominantly collagen fibres running in parallel. Found in: Ligaments (bone to bone), Tendons (muscle to bone), Aponeuroses (modified flattened tendons found on abdomen and back)

Question 31

What does a peripheral nerve consist of?

Answer 31

Bundles of nerve fibres called fascicles Dense connective tissue covering the nerve fibres and fascicles, binding them together (endoneurium, perineurium and epineurium) Small blood vessels (vasa nervorum) supplying the nerve tissue

Question 32

Describe the layers of the GI tract.

Answer 32

the mucosa (epithelium, lamina propria, and muscular mucosae), the submucosa, the muscularis propria (inner circular muscle layer, intermuscular space, and outer longitudinal muscle layer), and the serosa.

Question 33

Describe ion movements involved in a sodium calcium exchanger.

Answer 33

Na+ is pumped out in exchange for K+, Na+ comes back across the membrane down its conc. gradient, Ca2+ is exchanged for this Na+ to keep intracellular levels extremely low.

Question 34

What are the fat soluble vitamins?

Answer 34

A, D, E and K (A Dairy Eater Knows) Dairy is fatty

Question 35

What are the water soluble vitamins?

Answer 35

B complex, C

Question 36

Name the essential compounds, that are not energy yielding.

Answer 36

Vitamins, Minerals, Essential fatty acids, Essential amino acids, Ions and cholesterol etc.

Question 37

There are 6 electrolytes. Name them

Answer 37

K, Na, Cl, Ca, Mg, P

Question 38

What are the essential fatty acids? What are they needed for?

Answer 38

Omega 3, Omega 6. Needed for eicosanoids (a class of non-protein bioactive molecule) Examples of eicosanoids - prostaglandins, thromboxanes, leukotrienes These signal molecular mediated inflammation, pain and also modulate cell activities including cancer cell production

Question 39

What is vitamin k key for?

Answer 39

It is a blood clotting factor

Question 40

B6, 12, 7, 9 and 5 are ...... vitamins

Answer 40

Group transfer agent

Question 41

Vitamins A and D are precursors for?....

Answer 41

Hormones

Question 42

What are the three psychosocial theories for life development

Answer 42

Psychoanalytical, Cognitive and Sociocultural

Question 43

What are the four attachment stages in child development?

Answer 43

Asocial, indiscriminate, specific, multiple 6 weeks 7 months 9 months

Question 44

What is attachment, in terms of child development?

Answer 44

Deep and enduring emotional bond that connects one person to another across time and space

Question 45

Child development - compare secure attachment to insecure and resistant.

Answer 45

Secure = A child can be comforted back to normal after separation. Insecure/Resistant = Cannot be comforted or shows no anxiety at all

Question 46

What are the 3 main physical checks are done for children after birth and when?

Answer 46

Vision - Within 72 hours of birth Between 6-8 weeks old At 1 year or between 2-2.5 years At 4-5 years (pre-school) Hearing - Within a few weeks of birth 9 months - 2.5 years: parental concerns At 4 - 5 years (pre-school) Walking - Infants walk by 13 months of age Not walking by 18 months of age is a red flag. Cases such as down syndrome differ from this - Bottom shuffling ma be utilised by the baby for movement

Question 47

What is a condition called if it has an unknown cause?

Answer 47

Idiopathic

Question 48

What is a latrogenic condition?

Answer 48

A condition caused by medical personnel or procedures (treatment/diagnostic test) or that develops through exposure to the environment of a health care facility.

Question 49

Contrast hypertrophy and hyperplasia.

Answer 49

Hypertrophy Increase in the size of cells No new cells - just bigger Can be physiological or pathological Cells that don’t divide e.g. cardiac and skeletal muscle Examples: hypertension - cardiac muscle, exercise Hyperplasia Increase in the number of cells Cells that can divide; For example: breast development at puberty, liver regeneration after resection, wound healing E.g. psoriasis leads to thickened skin

Question 50

Name an example in which hyperplasia and hypertrophy occur simultaneously.

Answer 50

Uterine enlargement during pregnancy; Smooth muscle.

Question 51

What is the shrinkage of cell size called due to a loss of cell substance? example?

Answer 51

Atrophy e.g. immobilisation/ageing limb muscle

Question 52

What is involution? example?

Answer 52

Reduction in number of cells - apoptosis. Myometrium of uterus post partum

Question 53

What is Metaplasia and what can it lead to?

Answer 53

Change in type of cell Reprogramming of stem cells Survival mechanism in response to injury e.g. Smoking Specialised function is lost Can predispose to neoplasia

Question 54

What is neoplasia?

Answer 54

Not an adaptive response Permanent alteration of normal cellular growth pattern Abnormal proliferation in the absence/removal of stimulus Do not respond to normal signals controlling growth Dysregulated control mechanisms lead to uncontrolled proliferation

Question 55

What is the normal cell:plasma ratio in blood?

Answer 55

cells 45%; plasma 55%

Question 56

What is serum?

Answer 56

Plasma with clotting factors removed

Question 57

Name 2 components of blood plasma.

Answer 57

Albumin - Colloid osmotic pressure (oncotic pressure) Transporter Produced in liver Hypoalbuminemia (low) Hyperalbuminemia (high) Marker of inflammation Fibrinogen - Soluble precursor to Fibrin - clotting factor

Question 58

5 types of Leucocytes and the 2 categories they fall within? What are their functions?

Answer 58

Granulocytes Neutrophils Basophils Eosinophils Mononuclear leucocytes Lymphocytes Monocytes Neutrophil: leave circulatory system in response to tissue damage. Remove damaged tissue and kill and phagocytose invading organisms. Increased in bacterial infection. Eosinophil: Phagocytic (anti-body labelled material), elevated in allergic reactions and in parasitic infection Basophil: Release heparin and histamine that promote inflammation. Lymphocyte: immunologic response (antibodies). Increased in viral infections (infectious mononucleosis) Monocyte: Phagocytosis. Rarely elevated. In tissue is called a macrophage

Question 59

There are 6 blood analysis measurements. Name them.

Answer 59

Haematocrit (HCT): The fraction of the blood composed of red blood cells Erythrocyte sedimentation rate (ESR): The rate at which the red blood cells settle to the bottom of the test tube. Haemoglobin (Hb): Total amount of haemoglobin in the blood Mean cell haemoglobin (MCH): calculated using Hb and RBC Mean cell volume (MCV): average volume of a red blood cell Mean cell haemoglobin concentration (MCHC): average concentration of Hb in a given volume of packed red blood cells

Question 60

Discuss Mean Cell Haemoglobin ranges.

Answer 60

MCH varies in direct linear relationship with the MCV. Cells with less volume contain less Hb and vice versa MCH increase: B12 deficiency, folic acid deficiency, haemolytic anaemia MCH decrease: iron deficiency anaemia, thalassemia

Question 61

What is the suffix for MCV ranges?

Answer 61

-cytic

Question 62

What is the suffix for MCHC?

Answer 62

-chromic

Question 63

Name the 3 main types of anaemia and how they are caused.

Answer 63

microcytic anaemia - Iron deficiency alpha thalassaemia , beta thalassaemia - Haemoglobinopathies macrocytic anaemia - B12 / folate deficiency / pernicious anaemia

Question 64

What are the 5 cardinal signs of inflammation

Answer 64

Rubor, Calor, Tumor, Dolor, Functio laesa

Question 65

Describe the vascular events that occur during the onset of acute inflammation and what it allows.

Answer 65

Local blood vessels briefly contract and then dilate to slow the flow of blood to the area; mediated by mast cells (histamine) and endothelial cells (nitric oxide) Vascular permeability is increased allowing protein –rich plasma to leave the vessels and enter the tissue: the inflammatory exudate The slowing of flow allows neutrophils to come into contact with the (activated) endothelium

Question 66

What does inflammatory exudate contain?

Answer 66

Plasma and proteins (lots of fibrinogen) Neutrophils and some macrophages and lymphocytes

Question 67

Name the cells and proteins involved in inflammation.

Answer 67

Main cell is neutrophils but also ECs, macrophages, lymphocytes, platelets, fibroblasts, complement system.

Question 68

Explain neutrophil extravasation

Answer 68

Rolling - Selectins expressed on activated EC surface. Adhesion - Integrins expressed on neutrophil. Shape change - CD11 and 18 on EC bind Extravasation - PECAM1 on both cells facilitates the trans-endothelial emigration.

Question 69

Name the 4 enzyme cascades of plasma mediators

Answer 69

Coagulation system (activated Hageman factor - coagulation factor XII) converts fibrinogen into fibrin, also activates the kinin & fibrinolytic systems Kinin system e.g. bradykinin – mediates pain Fibrinolytic system e.g. plasmin – affects fibrin Complement

Question 70

Name the mediators of the following inflammatory responses: Vasodilatation

Answer 70

Vasodilatation - Histamine, prostaglandins, nitric oxide, bradykinin, PAF

Question 71

Name the mediators of the following inflammatory responses: Increased vascular permeability

Answer 71

Increased permeability -Histamine (transient), C3a, C5a, bradykinin, leukotrienes, PAF, nitric oxide (longer acting)

Question 72

Name the mediators of the following inflammatory responses: Neutrophil adhesion

Answer 72

Neutrophil adhesion - Adhesion molecules on endothelium are up-regulated by IL-1, IL-8, TNFα, PAF, LeukotrieneB4, C5a, chemokines

Question 73

Name the mediators of the following inflammatory responses: Neutrophil chemotaxis

Answer 73

Neutrophil chemotaxis - C5a, Leukotriene B4, bacterial components, chemokines IL-8

Question 74

Name the mediators of the following inflammatory responses: Fever

Answer 74

IL-1, TNF, prostaglandins

Question 75

Name the mediators of the following inflammatory responses: Pain

Answer 75

Prostaglandins, bradykinin

Question 76

Name the mediators of the following inflammatory responses: Tissue necrosis

Answer 76

Neutrophil lysosomal granule contents, Free radicals generated by neutrophils

Question 77

What mediators of inflammation are preformed in secretory granules and what cells produce them.

Answer 77

Histamine and serotonin - Mast cells, basophils and platelets and in platelets respectfully.

Question 78

Where are the following inflammatory mediators produced? • Histamine • Serotonin • Prostaglandins • Leukotrienes • Platelet-activating factor • Reactive oxygen species • Nitric oxide • Cytokines (e.g. TNF, IL-1) • Chemokines

Answer 78

• Histamine - Mast cells, basophils, platelets • Serotonin - platelets • Prostaglandins - Mast cells, leucocytes • Leukotrienes - Mast cells, leucocytes • Platelet-activating factor - Leucocytes, ECs • Reactive oxygen species - Leucocytes • Nitric oxide - Endothelium, macrophages • Cytokines (e.g. TNF, IL-1) - Macrophages, lymphocytes, endothelial cells, mast cells • Chemokines - Leucocytes, activated macrophages

Question 79

Most inflammatory mediators are cell derived, which aspects are plasma protein derived?

Answer 79

Complement and Factor XII activation (kinin and coagulation system)

Question 80

What are the main 4 acute phase proteins? (inflammation) and what are they responsible for?

Answer 80

Fibrinogen, C reactive protein (CRP), Serum amyloid A (SAA) Ferritin Responsible for systemic effects of inflammation

Question 81

Name 2 systemic effects of inflammation.

Answer 81

Mediated by cytokines (mainly from activated macrophages) act on the brain to increase temperature (fever), reduce appetite and increase fatigue. act on the bone marrow to increase the production of neutrophils (particularly in bacterial infection)

Question 82

Contrast tissue resolution and repair

Answer 82

Tissue resolution –restitution of normal tissue structure and function. If damage occurred to just the parenchyma. Repair by fibrosis – scar formation via granulation tissue formation and organisation. Occurs when damage occurs to the stroma as well.

Question 83

Name the 4 possible outcomes of acute inflammation

Answer 83

Tissue resolution Repair by fibrosis Abscess formation Chronic inflammation

Question 84

Tissue repair can depend on the regenerative capability of the damaged cells. What are the 3 types of regeneration ability/

Answer 84

Labile – replicate throughout life; skin and GI epithelium Stable – Non-dividing in normal circumstances but capable of regeneration – liver/kidney parenchyma Permanent – non-dividing cells; nerves, cardiac/skeletal muscle

Question 85

Name the 3 stages of healing by fibrosis.

Answer 85

Granulation tissue Macrophages, fibroblasts and new blood vessels (angiogenesis) Fibrosis and scar formation - Fibroblasts lay down matrix. Scar is formed as amount of collagen laid down is increased to strengthen the tissue Remodelling Over time the number of vessels is reduced and a pale scar remains

Question 86

Describe the proliferative phase of tissue repair (Skin)

Answer 86

Granulation tissue - Building tissue to fill the wound Fibroblasts secrete: Matrix components, Growth factors to stimulate angiogenesis Epithelial cells re-grow over the wound

Question 87

Describe wound contraction and remodelling.

Answer 87

Due to the action of fibroblasts laying down collagen and collagenases breaking down collagen to orientate for maximal tensile strength. Wound contraction Decreased vascularity

Question 88

What are the stages of tissue repair in skin?

Answer 88

Proliferation > wound contraction > remodelling

Question 89

Name a model disease regarding chronic inflammation.

Answer 89

Gastric Ulcers - Damage and repair occurring simultaneously

Question 90

What is innate immunity

Answer 90

General non specific immunity that does not evolve. e.g. PAMP recognition

Question 91

What are the primary lymphatic tissues?

Answer 91

Bone marrow and the Thymus Haematopoiesis and T cell maturation respectively

Question 92

What are the three pathways that activate the complement system?

Answer 92

Classical C1q binds to the Fc regions of these antibodies that are bound to microbial antigens. This activates C1r and C1s that are associated with C1q, leading to the conversion of C4 and C2. The fragments C4b and C2a combine to form C4b2a, which has C3 convertase activity. Lectin When mannose binding lectin interacts with microbes, it activates MBL-associated serine proteases that convert C4 and C2, generating C4b2a, aka C3 convertase.  Alternate Circulating C3b fragments, from the other pathways or spontaneous cleavage of C3, can be stabilised on microbial surfaces with another complement protein to form a version of C3 convertase

Question 93

Name the 5 antibody isotypes and their abilities.

Answer 93

M - first to be expressed, activates complement, pentamer interactions A - 2nd most abundant found in secretions such as saliva and breast milk, can act as a homodimer. D - Found on lymphocytes G - Most abundant, transplacental E - On basophils, mast cells - involved in allergy response.

Question 94

Compare and contrast MHCI and II

Answer 94

Class I - a1, 2, 3 and B2. CD8+ interaction, on every nucleated cell, endogenous antigens. Class II - a1, 2, B1, 2, CD4+ interaction, on APCs, exogenous antigens. Both formed in the endoplasmic reticulum.

Question 95

Name the major components of the lymphatic system.

Answer 95

Thymus, Lymph Nodes, Spleen, Mucosa associated lymphoid tissue, Specialised fixed phagocytes.

Question 96

Capillaries can be..., .... or ....

Answer 96

Continuous – no gaps in wall or basement membrane Fenestrated - gaps in wall but basement membrane still continuous e.g. small intestine, endocrine organs, kidney Sinusoidal (gaps in both wall and basement membrane e.g. spleen, liver, bone marrow)

Question 97

Name the main lymph nodes and where to locate them.

Answer 97

Cervical nodes - along internal jugular vein in the neck Pericranial- base of head Axillary nodes - in axilla- armpits Tracheal nodes Deep nodes - aorta, celiac trunk and mesenteric arteries Inguinal - pelvic area Femoral - inside leg in crotch

Question 98

Describe the draining of lymph into the venous circulation

Answer 98

Lymph from right side of head & neck + right upper limb and right thorax will drain into right lymphatic duct and into the junction between the right subclavian vein and right internal jugular vein – right venous angle Lymph from all other body regions drains into thoracic duct and then into the junction between the left subclavian vein and left internal jugular vein – left venous angle Lymph from lower half of body initially drains into cisterna chyli

Question 99

Describe lymph node structure and cell organisation.

Answer 99

Small bean-shaped structures that act as filters to trap and phagocytose particulate matter in the lymph. Macrophages in subcapsular sinus and medulla Clusters of lymphocytes e.g. B cells in lymphoid follicles, T cells in paracortical area

Question 100

Why are lymph nodes susceptible to secondary tumours?

Answer 100

Flow through lymph nodes is slow, so metastatic cells e.g. from a primary tumour in the breast may lodge in lymph nodes and grow as secondary tumours Lymph node removal + examination e.g. to assess tumour stage (spread of the cancer

Question 101

Cancers will spread first to their nearest nodes, name some examples.

Answer 101

Testicular cancer = lateral aortic nodes Breast cancer = axillary nodes (multiple groups) Genital herpes = superficial inguinal nodes Bronchitis = cervical lymph nodes

Question 102

What tests could you order to check for inflammation?

Answer 102

Erythrocyte sedimentation rate (ESR) • This is a separately ordered test from a FBC • It is a haematological test • This is a non-specific test for inflammation i.e. it will tell you something is going on but not the diagnosis. However, it can be helpful alongside the history, exam and the results of other tests • Baseline values tend to be higher in females and it rises with age Sample normal test ESR = 2 mm/h (< 12.0) C-reactive protein (CRP) • CRP is similar test to ESR though it measures only one acute phase protein rather than several in an ESR making it a more specific test • Again, it is a test for the presence of inflammation and changes more rapidly than the ESR • It may help diagnose or monitor activity in conditions such as polymyalgia rheumatica, cranial arteritis, rheumatoid arthritis and Crohn’s disease Sample normal test Serum CRP level = <0.5 mg/L (<5.0)

Question 103

There are 7 main blood tests that can be undertaken. Name them.

Answer 103

Full blood count, Erythrocyte sedimentation rate, C reactive protein, Urea and Electrolytes, Liver function, Thyroid function, Gycosylated haemoglobin.

Question 104

What are Erikson's 8 stages of psychosocial development?

Answer 104

Trust vs mistrust Autonomy vs shame and doubt initiative vs guilt industry vs inferiority identity vs role confusion intimacy vs isolation generativity vs stagnation integrity vs despair

Question 105

What are the 3 "health sectors" in relation to psychosocial opinions

Answer 105

Professional , folk and popular

Question 106

The skin has 5 main functions, name them

Answer 106

Protection from external damage: UV light, chemical, thermal and mechanical injury and resistance to sheer stress: thick skin Barrier: waterproof and a barrier to bacteria Sensation: touch, pressure, pain and temperature Metabolic: Synthesises vitamin D3, subcutaneous fat is a major energy store Thermoregulation: Insulation, heat loss by sweat evaporation and vasodilation

Question 107

Describe the main layers of the skin from bottom to top; and the main structures within them.

Answer 107

Hypodermis/subcutis: Adipose tissue and main blood supply. Dermis: Dense irregular connective tissue: fibroblasts, collagen I, elastin, blood, nerves and receptors. Divided into papillary and reticular dermis Epidermis: Stratified squamous epithelium (keratinised): keratinocytes

Question 108

Layers of the epidermis; bottom to top

Answer 108

Stratum basale: lowest layer of cells, separated from the dermis by a basement membrane to which they are attached cuboidal/low columnar shape attached to the basement membrane by hemidesmosomes and to adjacent basal cell by desmosomes a layer where mitosis is often observed and is the constant supply of keratinocytes as keratinocytes divide, new daughter cells migrate upwards forming the stratum spinosum Stratum spinosum: Contains so-called prickle cells which are large and polyhedral but flatten towards the junction with the next layer Cytoplasmic projections containing intracellular fibrils (Tonofibrils) that connect to other cells via desmosomes that look like prickles Lamellar bodies - secreted from keratinocytes, resulting in the formation of an impermeable, lipid-containing membrane that serves as a water barrier and is required for correct skin barrier function.  Stratum Granulosum: contain many keratohyalin granules and tonofibrils These are combined together to form the mature keratin complex Stratum lucidum: appears clear by light microscope, hence name – sometimes not visible A layer of dead cells between the granulosum and corneum Lysosomal enzymes in the cell burst and break down the cell organelles and nuclei Stratum corneum: a layer of flattened, dead cells containing only mature keratin Dying cells release a hydrophobic glyophopholipid which renders the skin surface waterproof These cells constantly need replacing and this comes from the lower layers – turnover depends on the skin site ie higher trauma, faster turnover

Question 109

What are the layers of the basement membrane zone

Answer 109

Lamina lucida –contains adherence proteins to cells above Lamina densa - principally type IV collagen Anchoring fibrils – arrays of type VII collagen – extend into papillary dermis

Question 110

Name a defect caused by the separation of the epidermis from the dermis with minimal shearing forces

Answer 110

Epidermolysis bullosa

Question 111

Epidermolysis bullosa can occur at three different locations in the basement membrane, name them and their consequences.

Answer 111

EB simplex: defective cytoskeleton - Good healing Junctional EB: defective hemidesmosomes - fatal Dystrophic EB: defective BM collagen - scarring

Question 112

There are 4 main skin cell types...

Answer 112

Keratinocytes: 95% of cells Stratified squamous keratinising epithelial cells Produce keratin – structural protein Melanocytes Pigment synthesising cells responsible for skin and hair colour Neural crest derived cells lying in the stratum basale Melanosomes in cytoplasm contain melanin and are passed to keratinocytes – scattering of UV light Langerhans cells: All layers and upper dermis-prominent in spinosum. Bone marrow derived. Dendritic, antigen presenting cells-migrate to regional lymph nodes and communicate with the immune system. Merkel cells: Clear cells in SB. Plentiful in touch areas. Connected to keratinocytes and afferent nerves. Neuroendocrine function

Question 113

What are the 2 layers of the dermis, top to bottom

Answer 113

Papillary dermis: a narrow zone just below BMZ of epidermis. conical papillae (rete ridges), richly vascularised (capillaries), lymph and nerve Reticular: Contains most of the dermal collagen. Horizontal collagen and elastin fibres Contains hair and gland structures

Question 114

What are rete ridges?

Answer 114

Downgrowths from the epidermis Found where there are more shearing forces e.g. palms of hands and soles of feet

Question 115

Describe hair follicles

Answer 115

Produce hair shafts (keratin) for thermoregulation and display. Growth from a hair bulb at the base Arrector pili muscle Sebaceous glands Majority associated with hair follicles. Secrete lipid mixture: sebum into hair follicle (waterproofing)

Question 116

Describe the two types of sweat gland

Answer 116

Eccrine: dermal-subcutaneous junction of all skin, produce sweat. Ducts open onto skin surface (thermoregulation) Apocrine: Localised (axilla/groin) scent production. Open into hair follicles above sebaceous duct. Functional at puberty

Question 117

Name and describe 3 cells that innervate the skin

Answer 117

Pacinian corpuscle (modified Schwann cells): subcutis, deep pressure and vibration Meissners corpuscle: papillary dermis, rapidly adapting mechanoreceptors - light touch/pressure sensation Ruffini corpuscle: mechanoreceptors, stretching of skin

Question 118

Name 2 bacterial infections of the skin

Answer 118

Impetigo: Staphylococcus/streptococcus Subcorneal blisters +/- pus Burst and spread: yellow crusting Highly contagious, children Cellulitis: Strep pyogenes/staph Superficial dermis, spreading factor Can lead to necrotising fasciitis Limbs – penetrating injury/bite

Question 119

Lifecycle of a virus

Answer 119

Attachment, entry, uncoating, macromolecular synthesis, assembly, and release.

Question 120

RNA must be .... polarised to be for translation to occur (viruses)

Answer 120

positively

Question 121

Name the two main virus capsid symmetries

Answer 121

Icosahedral, helical

Question 122

Viruses can have 4 different effects on cells

Answer 122

Acute cell death Chronic (a.k.a. persistent) infection - Continuous viral replication within cell, but cell survives. Latency- No virus replication, Viral genome present, but no production of viral proteins, Once infected, always infected, e.g. herpesvirus Virus replication can be reactivated Primary and secondary infections Transformation – immortalisation of the cell Eg Epstein-Barr virus (EBV) - cancer potential

Question 123

3 effects of antibody binding to viruses and infected cells

Answer 123

Antibody - blocks binding and entry to cells (neutralization) - activates intracellular degradation via TRIM21 Antibody + complement - damage to enveloped viruses - opsonisation for phagocytosis Antibody bound to infected cells - antibody-dependent cellular cytotoxicity

Question 124

What is antibody neutralisation

Answer 124

Block attachment through steric interference, capsid stabilisation, structural changes.

Question 125

Intracellular degradation facilitated by TRIM21

Answer 125

Antibody recognition > TRIM recruitment > ubiquitination > proteasome degradation

Question 126

Antigenic shift vs drift

Answer 126

Shift is mixing of 2 separate viruses RNA/DNA, Drift is accumulation of mutations over time.

Question 127

what are and what is the Action of interferons in viral infections

Answer 127

Signals to neighbouring cells to undergo apoptosis, destroy RNA and reduce protein synthesis and activate immune cells

Question 128

How is HLA1 involved in immune recognition

Answer 128

HLA I expression is lowered in some virally infected cells so natural killer cells can recognise it as abnormal and needs killing

Question 129

Killer cells kill cells via ...., .... and .....

Answer 129

Perforins (osmotic lysis), granzymes and the Fas ligand (apoptosis via caspase and endonucleases)

Question 130

On which side of the neuronal membrane are Na+ ions more abundant?

Answer 130

: The neuronal membrane potential depends on the ionic concentrations on either side of the membrane. K + is more concentrated on the inside of the neuronal membrane, whereas Na+ and Ca2+ are more concentrated on the outside

Question 131

There is a much greater potassium K+ concentration inside the cell than outside. Why, then, is the resting membrane potential negative?

Answer 131

The resting membrane potential is negative because the neuron is filled with negatively charged molecules, such as proteins, that do not traverse the cell membrane through channels the way ions do.

Question 132

Which ions carry the early inward and late outward currents during the action potential?

Answer 132

During the early part of the action potential, the influx of sodium ions across the membrane briefly depolarizes the membrane. The brief inward sodium current is a consequence of opening the voltage-gated sodium channels for only 1 msec. Membrane repolarization is the result of potassium efflux, which is the outward potassium current because of opening voltage-gated potassium channels after a delay of 1 msec.

Question 133

How does the conduction velocity of action potential vary with axonal diameter? Why?

Answer 133

The speed of action potential depends on how far depolarization spreads ahead of action potential. This, in turn, depends on the physical characteristics of axons. The two paths that a positive charge can take are inside an axon and across the axonal membrane. When the axon is narrow with many open pores, more of the current flows across the axonal membrane and is lost. When the axon is wide with a few open pores, the current flows inside the axon. The farther down the axon the current flows, the farther ahead of the action potential the membrane will be depolarized and the faster the action potential will propagate. As a result, the conduction velocity of axons increases with the diameter of axons.

Question 134

Voltage-gated Na+ channels can be in 4 states

Answer 134

Resting (inactivated) Open (activated) Inactivated Closed and inactivated - absolute refractory period

Question 135

Absolute vs relative refractory period

Answer 135

Absolute is all gates inactivated, prevents refiring. Relative is a few are inactivated so a big stimulus could produce an action potential.

Question 136

Multiple sclerosis

Answer 136

Autoimmune, attacks and hardens myelin sheath > slows nerve conduction > weakness, coordination, vision and speech issues.

Question 137

Name the 3 main glial cells

Answer 137

Microglia - Remove debris from dead or degenerating glia Astrocytes - Regulate the chemical content of the extracellular space. e.g. neurotransmitter removal Oligodendrocytes (Scwann cells in the PNS)

Question 138

4 lobes of the brain

Answer 138

From front to back and around Frontal - cognition and motor control Parietal - Sensory Occipital - vision Temporal - auditory and memory

Question 139

How many cranial nerves are there?

Answer 139

12

Question 140

How many pairs of spinal nerves are there?

Answer 140

31: 8 cervical (C) 12 thoracic (T) 5 lumbar (L) 5 sacral (S) 1 coccygeal (Co)

Question 141

When looking at a thoracic X-Ray, what is ABCDE

Answer 141

Airways Bones Cardiac region Diaphragm Everything else

Question 142

What are the colours on X-Rays of Bone, Fat, Soft tissue, Air and Man made items

Answer 142

Bone = White Soft tissue = Grey Fat = Dark grey Air = Black Manmade = Bright White

Question 143

Is posterior anterior or AP preferred?

Answer 143

PA is preferred - less magnification

Question 144

Weak acid drug - stomach and intestine absorption?

Answer 144

A- + H+ -> AH Stomach At low pH, [H+] is high, equilibrium goes towards HA Very little ionised > lots absorbed Intestine At high pH, [H+] is low, More ionised > little absorbed Less absorbed

Question 145

Weak base - stomach and intestine absorption

Answer 145

B + H+ -> BH+ Stomach At low pH, [H+] is high, Equilibrium goes towards BH+ Lots ionised Little absorbed Intestine At high pH, [H+] is low, Less ionised More absorbed

Question 146

Bioavailability

Answer 146

Amount of drug that reaches systemic circulation with respect to the amount administered

Question 147

What is first pass metabolism

Answer 147

Many drugs are metabolised by enzymes in the gut wall or the liver.

Question 148

Name two routes of administration that avoid first pass metabolism

Answer 148

Mouth - Sub-lingual, Buccal Rectal

Question 149

Routes of administration and advantages

Answer 149

Sub-lingual – glyceryl trinitrate Undergoes first pass metabolism Need quick response Sub-cutaneous – local anaesthetics Acting locally Can be given with vasoconstrictor to delay systemic absorption Intra-muscular depot preparations – contraceptives Gradual release  sustained concentrations Convenience Rectal – anti-epileptic drugs Diazepam for epilepsy when patient is fitting continuously Topical – anti-inflammatories Ibuprofen, avoids irritation to stomach Corticosteroids, to avoid systemic side effects Inhalation – asthma COPD drugs Direct to target, minimises side effects Intra-articular – anti-inflammatories Corticosteroids, direct to target, avoids systemic side effects

Question 150

Factors that affect absorption from the gut

Answer 150

Gastric emptying Gastrointestinal motility Blood flow Particle size and formulation Extended-release formulations Enteric coatings Physicochemical factors e.g. solubility, molecular weight, binding to calcium (esp. in milk) or fat in food Metabolism (enzyme-catalysed reactions)

Question 151

Volume of distribution

Answer 151

volume of plasma that would contain the total body content of the drug at a concentration equal to that in the plasma.

Question 152

Describe drug solubility in Blood > interstitial > inside cells with respect to Vd

Answer 152

Hydrophilic > very lipid soluble 3.5 L/70kg > 14 > 40 > 40<

Question 153

Phases of drug metabolism

Answer 153

Phase 1 reactions often catalysed by cytochrome P450 enzymes (CYP). Important for non-polar drugs e.g. CYP1A2 - caffeine, paracetamol Phase 2: Conjugation - Increases solubility in water and therefore excretion in the kidney

Question 154

Drug metabolism in the liver depdnds on

Answer 154

Perfusion Plasma protein binding Secretion into bile Presence and activity of transporters and enzymes

Question 155

Clearance (drug)

Answer 155

the volume of plasma from which all the drug molecules would need to be removed per unit time to achieve the overall rate of elimination of drug from the body

Question 156

Name the stages of cell growth

Answer 156

GO – No cellular activities regarding cell growth G1 – Cell grows to full size S – DNA synthesis for doubling genome (chromosome) G2 – Rapid cell contents production. Final Check for errors Mitosis – Cell divides Cytokinesis – Cell separates into daughter cells

Question 157

Describe a regulatory pathway regarding the cell cycle

Answer 157

E2F – S phase gene transcription factor - normally bound by retinoblastoma protein (Rb) rendering E2F inactive Under favourable conditions, Cyclins will be produced and bind to CDK Cyclin / CDK complex phosphorylates Rb Phosphorylated Rb changes conformation and uncouples from E2F E2F is free to act as transcription factor for S phase gene transcription

Question 158

Name example enzymes involved in S phase initiation in the cell cycle

Answer 158

Critical initiation of S phase by retinoblastoma protein phosphorylation regulated by Cyclin D / CDK4/6 and Cyclin E / CDK2 complexes

Question 159

What are the stages of mitosis?

Answer 159

Prophase – Chromosomes start condensing and organised. Spindle fibres formed. Nuclear membrane resolves Prometaphase – Chromosomes attached to spindle fibres. Chromosomes further condense Metaphase – Chromosomes start aligning in centre. Sister chromatids facing opposite poles Anaphase - Separation of sister chromatids then migrate to opposite poles Telophase - Chromatids in positions and start decondensing, Formation of nuclear membrane, Spindle fibres resolve Cytokinesis - Cytoplasm divides Completion of cell division Two identical cells formed

Question 160

Two types of microtubules projecting from the microtubule organising centres

Answer 160

Polar microtubules and the kinetochore microtubules (K fibres)

Question 161

Cell cycle checkpoints

Answer 161

Each stage of cell cycle cannot progress without checking for: DNA damage DNA replication error Spindle fibre assembly and chromosome alignment

Question 162

Affinity

Answer 162

Affinity: how tightly the drug binds its receptor. the concentration required to occupy the receptor

Question 163

Efficacy

Answer 163

maximum response

Question 164

Potency

Answer 164

Concentration required to give half the maximum response (EC50).

Question 165

Allosteric antagonists are as good as competitive antagonisits. T/F?

Answer 165

False, may not be able to reduce response totally.

Question 166

Ligand gated ion channel example

Answer 166

Nicotinic Acetylcholine, GABA, Glutamate Small molecules Fast neurotransmission e.g. nerve to muscle (nicotinic), nerve to nerve. Movement of ions through channel  electrical activity

Question 167

GPCR Example

Answer 167

Muscarinic ACh, dopamine, adrenaline, noradrenaline, serotonin, opiods, Small molecules and peptides Neurotransmission, modulation of neurotransmission, Activation of enzymes and modulation of ion channels  signalling cascades

Question 168

Tyrosine Kinase example

Answer 168

EGF, VEGF, PDGF, TNFa, Interleukins, Interferons Peptides and proteins Regulate cell growth, proliferation, death Activation of protein signalling cascades leading to change in gene transcription

Question 169

Nuclear receptor example

Answer 169

Corticosteroids (e.g. cortisol) Sex steroids (e.g. oestrogen and testosterone) Thyroid hormone Steroids and thyroid hormone Regulate gene transcription Gene transcription  synthesis of mRNA and protein

Question 170

Consequentialism

Answer 170

Judge action by its outcome e.g. move carriage to kill1 instead of 5 is good.

Question 171

Deontology

Answer 171

Moral of the action itself - independent of the outcome e.g. dont move the carriage as you will actively be killing the 1 person

Question 172

Virtue ethics

Answer 172

What would a good person do

Question 173

Autonomy

Answer 173

Patient has ultimate decision making responsibility.

Question 174

Beneficence

Answer 174

Best interest of the patient

Question 175

Non-malifecence

Answer 175

Do not harm

Question 176

Justice

Answer 176

Act on Legality, rights, and distributive care

Question 177

Describe serous membranes

Answer 177

line the inside of the body wall and cover many organs Formed from embryonic mesoderm Mesothelium: simple squamous epithelium + thin layer of connective tissue with blood vessels Inner visceral layer, outer parietal layer

Question 178

What is superficial fascia

Answer 178

Deep to skin: loose connective tissue and fat (adipose) Variable thickness Contains collagen, fat cells & elastic tissue

Question 179

What is deep fascia

Answer 179

Surrounds muscles Fibrous, strong and tough sheet Forms routes for infection spread Forms compartments: can have consequences during a bleed

Question 180

What is fascia

Answer 180

Connective tissue layers which can be thin, thick, fatty or loose

Question 181

Name examples of anatomical variation

Answer 181

Differences in build and shape (body habitus) Palmaris longus muscle Situs inversus and dextrocardia Renal agenesis: one kidney at birth instead of two

Question 182

What are the vertebral levels

Answer 182

7 Cervical 12 Thoracic 5 Lumbar Sacrum (5 fused) Coccyx (3/4 fused)

Question 183

Distinguishing features of the vertebrae

Answer 183

Spinous processes point inferiorly Heart-shaped vertebral bodies Vertebral bodies have costal facets for articulating with head of rib T1 – T10 transverse processes have transverse costal facets for articulating with tubercle of the corresponding rib

Question 184

How many ribs and which are true, false or floating

Answer 184

12 Ribs 1-7 = true ribs Articulate with the sternum via their own costal cartilage Ribs 8-10 = false ribs Articulate with the sternum via shared costal cartilage Ribs 11 & 12 = floating ribs Do not articulate with sternum

Question 185

Describe the anatomy of a typical rib

Answer 185

Ribs 3-9 Head: articulates with vertebral body at same level plus the vertebral body above Neck Tubercle: articulates with transverse process of vertebra at same level Costal angle Body or shaft with costal groove running inferiorly

Question 186

Describe the 1st rib

Answer 186

Flat, sickle-shaped appearance Single facet on head for articulation with T1 vertebral body only Subclavian grooves Scalene tubercle (anterior scalene muscle)

Question 187

Describe the 2nd rib

Answer 187

Longer than first rib Has two facets on head – articulates with T1 and T2 vertebral bodies Tuberosity for serratus anterior muscle

Question 188

Describe the 10th-12th ribs

Answer 188

10th – 12th ribs Single facet on head for articulation with one vertebral body e.g. T10 for 10th rib

Question 189

What are real spaces?

Answer 189

keep their structure when empty e.g. trachea (airway)

Question 190

What are potential spaces?

Answer 190

small, flattened spaces that have the potential to become much larger: Serous membrane cavities e.g. pleural cavity Fascial planes

Question 191

Name the 3 structures of the sternum

Answer 191

Manubrium, body and xiphoid process

Question 192

Describe features of the sternum and where they lie in relation to the rest of the body

Answer 192

Manubrium has attachments for the clavicles and first costal cartilages (for first ribs) Suprasternal (jugular) notch is at T2 vertebral level Sternal angle (manubriosternal joint) is at the level of the intervertebral disc between the T4 and T5 vertebrae Attachments for second costal cartilages Body of the sternum is between T5-T9 vertebral levels Xiphoid process is at T10 vertebral level

Question 193

What does the thoracic plane at the sternal angle signify in the mediastinum

Answer 193

The start and end of the arch of the aorta The site where the superior vena cava enters the heart The pulmonary trunk The bifurcation of the trachea into the left and right main bronchi

Question 194

Describe the formation of the morula

Answer 194

After 3 days of cell division, 12-16 cells are evident. The embryo is now called a morula, because it looks like a mulberry. The inner cells of the morula are called the inner cell mass, and the surrounding cells are referred to as the outer cell mass.

Question 195

Describe the formation of the blastocyst

Answer 195

Blastocyst forms an inner fluid filled cavity called the blastocele. Inner cells form the embryoblast at one pole, outer cell mass flattens and forms the trophoblast as a sphere around the whole thing.

Question 196

What is a teratogen?

Answer 196

An agent or factor which causes malformation of an embryo or disruption to a normal developmental process or deformation of a part of the body or dysplasia/abnormal organisation of cells in tissues resulting in a congenital abnormality/birth defect:

Question 197

What can prevent neural tube defects?

Answer 197

by taking 0.4 milligrams of folic acid daily

Question 198

Name different types of teratogens with examples

Answer 198

Infections Sexually transmitted e.g. chlamydia – premature rupture of membranes, preterm labour Non-sexual infections e.g. rubella (German measles) – heart defects Zika virus infection - microcephaly Maternal diet Lack of folic acid – neural tube defects (e.g. spina bifida) Maternal drugs Methotrexate (immunosuppressant used in rheumatoid arthritis): skeletal defects involving the face, cranium, limbs and vertebral column Environment Ionising radiation e.g. X-rays: microcephaly, mental deficiency, skeletal anomalies, delayed growth, cataracts Maternal health Alcohol: fetal alcohol syndrome: IUGR, mental deficiency, microcephaly, ocular anomalies, joint abnormalities, short palpebral fissures

Question 199

When are teratogens most likely to cause defects?

Answer 199

Embryonic weeks 3 to 8 are when teratogens are most likely to cause defects, as this is when organogenesis

Question 200

When are teratogens most likely to affect organ size?

Answer 200

After week 9

Question 201

Describe implantation of the blastocyst into the endometrium.

Question 202

Describe bilaminar embryonic disc formation

Answer 202

Embryoblast forms two layers; epiblast and the hypoblast.

Question 203

Describe amniotic cavity formation

Answer 203

Cells from the epiblast layer form the lining (amnion) of the amniotic cavity

Question 204

Describe primary and secondary umbilical vesicle formation

Answer 204

Blastocele becomes the primary umbilical vesicle upon implantation. Splits into the primary remnant and the secondary by the extra embryonic coelom

Question 205

Describe trilaminar embryonic disc formation

Answer 205

The process begins with formation of the primitive streak on the surface of the epiblast Cells of the epiblast migrate toward the primitive streak They then slip beneath it in a process called invagination Some invaginating cells displace the hypoblast, creating the endoderm. Other cells come to lie between the epiblast and newly created endoderm to form mesoderm Cells remaining in the epiblast form ectoderm

Question 206

What does the endo, meso and ectoderm give rise to?

Answer 206

The ectoderm gives rise to the nervous system (neuroectoderm) and the epidermis of the skin (surface ectoderm). The mesoderm gives rise to the muscle cells and connective tissue in the body, the dermis of the skin and linings of the body cavities (serous membranes e.g. pleura, pericardium, peritoneum). The endoderm gives rise to the epithelial lining of the digestive and respiratory systems and many internal organs (eg liver, pancreas, thyroid gland).

Question 207

Describe embryo neuralation

Answer 207

The notochord induces the overlying ectoderm to thicken and form the neural plate. The neural plate lengthens and the lateral edges elevate to form the neural folds with the neural groove lying in the midline. The neural folds approach each other in the midline and begin to fuse. The folds fuse in a cranial and caudal direction from the cervical (neck) region The neural tube is formed. The two ends of the neural tube eventually close The rudimentary central nervous system (brain and spinal cord) is formed

Question 208

What do neural crest cells give rise to?

Answer 208

Neural crest cells from the trunk region migrate to form melanocytes in the skin, sympathetic neurons and ganglia of the autonomic and enteric nervous system, Schwann cells and cells of the adrenal medulla. Neural crest cells from the cranial end form glial nerve cells, parts of the connective tissues of the face and skull and neurons of cranial ganglia.

Question 209

Describe the changes that the mesodermal layer undergoes after gastrulation.

Answer 209

The mesodermal germ layer comes to form either side of the developing notochord (day 17) The mesoderm begins to thicken to form the paraxial mesoderm. Laterally, the mesoderm remains thinner and forms the lateral plate mesoderm The lateral plate mesoderm begins to break down and divide into two layers (20 days) The 2 layers are called the somatic or parietal mesoderm and the visceral or splanchnic mesoderm : The splitting of the lateral plate mesoderm (together with folding of the embryo) will eventually create the intraembryonic coelom or cavity

Question 210

What do the somites form?

Answer 210

The sclerotome – which forms the vertebrae and ribs The myotome – which forms the skeletal muscles of the back and limbs The dermatome – which ultimately forms the dermis for the skin of the back and body wall

Question 211

Describe embryo lateral folding.

Answer 211

The lateral body walls come together anteriorly in the midline and pinch the yolk sac as they do so. Eventually the lateral body walls close completely: The only area of the embryo where the lateral walls don’t completely close is at the umbilical cord Part of the endoderm is incorporated into the body of the embryo and forms the primitive gut tube The intraembryonic coelom/cavity has been formed) – this single cavity will eventually divide to form the pericardial, pleural and peritoneal cavities.

Question 212

What mesoderm covers the intraembryonic cavity wall and the gut tube

Answer 212

The intraembryonic cavity wall is lined with parietal mesoderm and the gut tube (and eventually other organs) is lined with visceral mesoderm.

Question 213

Describe longitudinal folding

Answer 213

At the same time as lateral folding, lengthening of the neural tube causes the embryo to curve into the foetal position as the head and tail regions move ventrally and longitudinal folding of the embryo occurs As the head and tail longitudinal folding occurs, the amnion is pulled down to surround the embryo which then comes to lie within the amniotic cavity: As folding continues the heart and the oropharyngeal membrane (where the mouth will form) turn under onto the ventral surface of the embryo As longitudinal folding continues, the yolk sac is ‘pinched’ until the connection with the gut tube is narrowed to form the omphaloenteric (or vitelline) duct

Question 214

Outline organogenesis in weeks

Answer 214

4 - the neural tube continues to close; somites continue to develop (21-29 by now); 1-3rd pharyngeal arches have developed (form the head and neck); the heart, liver and early limb buds have begun to form, the tongue has begun to form, the heart tubes have looped (and beats); the early lung buds develop. Week 5: 30 somites are present; the developing eye and ear are visible; the early nose and face has started to form; the stomodeum (the future mouth) is evident, the early heart chambers are forming; the liver is expanding; paddle-shaped limb buds are evident. Week 6: further development of the limbs showing hand buds and digital rays; the elbow joint forms; parts of the face have developed (oral and nasal cavities); the early inner and middle ear structures are forming; the gut tube is elongating and looping (normal herniation of the gut is evident due to the rapidly growing intestines). Week 7: the eyelids have formed; the external ear is evident; partial separation of the digital rays is evident but the hand plates are still webbed; the foot plate is present; the trunk has straightened; further genital development is evident; palate formation has started. Week 8: the head is more rounded, the hands and feet come closer together and touch each other; coordinated limb movements are seen; gut herniation is still evident (they return to the abdominal cavity during the 10th week); accurate sex identification is not possible yet.

Question 215

Describe the location of parasympathetic ganglia

Answer 215

Preganglionic neurones are in grey matter of brainstem ( midbrain, pons, medulla) OR lateral horn of spinal cord grey matter from S2-4 (hence craniosacral) Long, synapse with postganglionic neurones at or near organ Cell bodies are in distinct ganglia near or on their final target organ Short, synapse on target organ

Question 216

Describe the location of sympathetic ganglia

Answer 216

Pre-ganglionic cell bodies are in the lateral horn of spinal grey matter from T1-L2 (hence thoracolumbar) Short, synapse with postganglionic neurones near spinal cord Cell bodies are in the sympathetic chain or other named ganglia Long, synapse on the target organ

Question 217

Which part of para and sympathetic neurones are myelinated?

Answer 217

preganglionic neurones

Question 218

Describe nerve routes in the sympathetic chain

Answer 218

Pre-ganglionic fibres pass into the chain via the white ramus communicans (white because fibres are myelinated) Fibres concerned with head and thorax terminate with post-synaptic cell bodies in sympathetic chain. These return to spinal nerve via grey ramus communicans (grey because unmyelinated) Pre-ganglionic fibres concerned with pelvic and abdominal viscera pass uninterrupted through chain to the plexuses - to the corresponding post-ganglionic neurones

Question 219

Name the midbrain ps nuclei

Answer 219

Edinger-Westphal nucleus of the oculomotor nerve (CN III) Provides parasympathetic innervation to iris & muscles of ciliary body (constricts pupils and change shape of lense)

Question 220

Name the PS nuclei of the Pons

Answer 220

Superior salivatory nucleus of the facial nerve (CN VII) Provides parasympathetic innervation to lacrimal glands (to produce tears) and sublingual and submandibular salivary glands (to produce saliva)

Question 221

Name the medulla nuclei

Answer 221

Inferior salivatory nucleus of glossopharyngeal nerve (CN IX) Provides parasympathetic innervation to parotid salivary gland (to produce saliva) Nucleus ambiguus (axons travel in CN X) Provides parasympathetic innervation to larynx, pharynx & heart Dorsal motor nucleus of vagus nerve (CN X) Provides parasympathetic innervation to lungs, pancreas, GI tract & heart

Question 222

What brain structure regulates the ANS?

Answer 222

Hypothalamus via the Dorsal Longitudinal Fasciculus being the principle tract.

Question 223

Name two disorders of the ANS

Answer 223

Postural hypotension - Dizziness, damage to sympathetic nerves supplying blood vessels due to diabetes or syphilis e.g.. Horners syndrome - Drooping of upper eyelid, miosis, anhidrosis, interuption of s nerve to eye. CAUSED BY BRAIN LESIONS OR LUNG cancer (affects ganglia)

Question 224

Diagnostic test specificity

Answer 224

the ability of the test to correctly identify people without the disease; i.e., the percentage of individuals without the disease who have negative test results. True Negative/ (True Negative+ False Positive)

Question 225

Diagnostic test sensitivity

Answer 225

the ability of the test to correctly identify people with the disease; i.e., the percentage of individuals with the disease who have positive test results. True Positive/ (True Positive+ False negative)

Question 226

When is high sensitivity good and when is high specificity

Answer 226

High sensitivity useful (e.g., screening breast cancer, HIV) Life-threatening diseases (if untreated) Improvement in survival rate with early treatment Is ok to “over diagnose” (more false positives) as all positives will have further testing – screening High specificity useful (e.g. Down syndrome during pregnancy) Not life-threatening if untreated Subsequent tests/treatments are too invasive or have serious side effects High cost of treatment Low pre-test probability (prevalence)

Question 227

Positive predictive value

Answer 227

True positive/(True Positive + False Positive)

Question 228

Prevalance =

Answer 228

(TP + FN)/ (TP + FN + FP + TN)

Question 229

What is the kappa ratio

Answer 229

Measuring the extent to which agreement exceeds that expected by chance requires a measurement statistic called the kappa.

Question 230

Apoptosis as a physiological event

Answer 230

Embryological development (GI lumen, digits) Involution of hormone dependant tissues (breast/uterus) Maintenance of cell number in tissues with high cell turnover (intestinal epithelium) Elimination of unwanted individual cells (neutrophils /lymphocytes after inflammation/immune response)

Question 231

Apoptosis as a pathological event

Answer 231

DNA damage (eg radiation, cytotoxicity, viral infection. p53) Misfolded proteins: due to intrinsic or extrinsic mechanisms accumulate in RER and cause stress (eg death of nerve cells in neurodegenerative conditions) Growth factor deprivation

Question 232

Morphology of apoptosis

Answer 232

Degradation of cytoskeletal framework Fragmentation of DNA Loss of mitochondrial function Nucleus shrinks (pyknosis) and fragments (karyorrhexis) Cell shrinks Cell fragments: apoptotic bodies Membrane intact but attracts phagocytes – secondary necrosis

Question 233

Intrinsic pathway of apoptosis

Answer 233

Cell injury detected by Bcl-2 sensors. The Bcl-2 family - apoptotic regulators B-cell lymphoma gene 2 (Bcl-2) – controls the permeability of mitochondria Anti-apoptotic members e.g. Bcl-2, Bcl-XL Pro-apoptotic members e.g. Bax, Bak, Bok Balance of pro- and anti- apoptosis proteins determine mitochondrial membrane permeability Increased permeability = cytochrome C release Cytochrome C activates caspases > endonucleases >cytoskeleton breakdown

Question 234

Extrinisic pathway of apoptosis

Answer 234

The Fas family - cell death receptors Part of the Tumour Necrosis Factor (TNF) and Neuronal Growth Factor (NGF) receptor family Cell death receptors differ from the rest of the family by the presence of the intracellular Death Domain (DD): Fas, TNFR1 Fas Ligand (FasL) - membrane protein expressed on activated T lymphocytes. Ligands bind to Fas or TNF receptor. Cluster and activate caspases via adapter proteins.

Question 235

Morphology and mechanism of reversible injury

Answer 235

Swelling - hydropic change Earliest manifestation of almost all forms of cell injury As a result of sodium and water influx into cell Membrane damage rendering it more permeable to sodium Membrane sodium pump damaged Membrane sodium pump deprived of ATP Fatty change Organs actively involved in lipid metabolism e.g. liver (steatosis) Accumulation of triglyceride-filled vacuoles due to disruption of metabolic pathways – toxic injury e.g. alcoholism

Question 236

Pathological apoptosis examples

Answer 236

Bcl-2 overexpressed in many cancers: lymphomas, small lung cell carcinoma, chronic lymphocytic leukaemia, melanoma Apoptosis deregulated: prostate, ovarian, cervical, bladder, breast, colorectal, pancreatic and gastric cancers Too little apoptosis: autoimmune diseases, cancer, chronic inflammatory diseases Too much apoptosis: immunodeficiency (e.g. AIDS), neurodegenerative diseases

Question 237

What is necrosis

Answer 237

Continuation of reversible injury: severe swelling of mitochondria, lysosomes and membrane damage Lysosomal enzymes are released and the organelles are destroyed (autolysis) Necrosis is followed by inflammation

Question 238

Coagulative necrosis

Answer 238

Most common Due to interruption of vascular supply (ischaemia) - infarction Common in solid organs e.g. heart and kidney Denaturation of protein Gross appearance: firm, dry and slightly swollen (cooked) Histology appearance: pale staining with loss of nuclei and cellular components but retention of tissue architecture

Question 239

Liquefactive/colliquative necrosis

Answer 239

Seen in the brain (primary event) and in infections (secondary to infection of necrotic tissue with pyogenic organisms: abscess) Due to hydrolytic lysosomal enzymes. Neutrophils contributing to the liquefaction (from hydrolases) Gross appearance: local accumulation of protein-rich, semifluid material. Histology: No architecture, proteins and phagocytes

Question 240

Caseous necrosis

Answer 240

Seen in tuberculosis Combination of coagulative and liquefactive necrosis Gross appearance: yellow-white cheese-like Histology: amorphous proteinaceous mass, lysed cells with no cell outlines/architecture. Surrounded by a granulomatous inflammation

Question 241

Gummatous necrosis

Answer 241

Gross: Firm and rubbery dead tissue Histology: no architecture, amorphous proteinaceous mass-like caseous Only referred to in the context of syphilis infection

Question 242

Gangrene

Answer 242

Necrosis of all tissue in an area Wet gangrene-coagulative necrosis from lost blood supply + liquefactive from infection (often bacterial) Dry gangrene- coagulative necrosis from anoxia (diabetes mellitus/atherosclerosis)

Question 243

Fibrinoid necrosis

Answer 243

Seen in blood vessels in the case of immune reactions e.g. arteries in the case of vasculitis/malignant hypertension Necrotic area of smooth muscle layer in the artery is filled with fibrin leaked from vessels Histological only

Question 244

Fat necrosis

Answer 244

Necrosis of adipose tissue Due to trauma (breast) or lipolytic enzymes (pancreas). Gross: foci of hard, yellow material Histology: Necrotic fat cells and inflammation

Question 245

Haemorrhagic necrosis

Answer 245

Blockage of venous drainage - leads to congestion and failure of arterial perfusion. Gross: dead tissues infiltrated by large numbers of extravasated red cells. Histology: congested tissues with abundant RBCs

Question 246

What is ischaemia?

Answer 246

Impaired vascular perfusion, depriving the affected tissue of vital nutrients, especially oxygen Tissue effects can be reversible, but is dependent on: duration of the ischaemic period-brief ischaemic episodes may be recoverable metabolic demands of the tissue-cardiac myocytes and cerebral neurones are the most vulnerable

Question 247

What is infarction?

Answer 247

Death (necrosis) of tissue as a result of ischaemia

Question 248

Cellular events in ischaemia

Answer 248

Reduction or loss of O2 - ATP production reduced - failure of energy-dependent processes Membrane pumps fail (require energy) - Na+ and H2O influx – swelling Anaerobic glycolysis – increased lactic acid – decreased pH – compromised enzyme environment ER swelling – ribosome detachment – decreased protein synthesis Organelle membrane damage: Increased cytosolic Ca2+ (from mitochondria and ER) Lysosomal breakdown releases enzymes (proteases etc.) - digestion of cell components

Question 249

Reperfusion injury

Answer 249

Further effects of ischaemia when perfusion is re-established Oxygen free radicals built up Depletion of scavengers (antioxidants e.g. vitamin E) Excess generation (e.g. mitochondria, neutrophils) Build-up of metabolic by-products (ATP use) – O2 influx – conversion to reactive oxidants DNA, protein and lipid damage Additional tissue damage due to increased numbers of inflammatory cells – increased secondary inflammation

Question 250

Tissue susceptibility to infarction

Answer 250

Availability of blood supply Anastomosis – collateral blood supply Watershed area – vulnerable in hypotension Infarct shape dependent on perfusion territory of the occluded blood supply e.g. wedge-shaped Metabolic activity of tissue Neurones and cardiac myocytes are most vulnerable to ischaemia - high metabolic demand Regenerative ability Tissues which can regenerate (labile, stable) can recover, non-dividing tissue (permanent) will have scar tissue

Question 251

What are the main energy sources for the heart when: 1 Immediately after a meal? 2 Between meals in a steady state? 3 During starvation or prolonged exercising?

Answer 251

1 = glucose (glycolysis) 2 = Fatty acids (β-oxidation) 3 = Ketone bodies and fatty acids

Question 252

What are the fates of pyruvate in both aerobic and anaerobic respiration?

Answer 252

In aerobic respiration it is converted into acetyl-CoA which enters the citric acid cycle to make NADH and ATP In anaerobic respiration it can be used to regenerate NAD+ which can be used to make small numbers of ATP. This requires the enzyme lactate dehydrogenase which produces lactate and NAD+ from pyruvate and NADH. This has the effect of lowering the pH

Question 253

What are the clinical signs of cardiac ischemia?

Answer 253

Chest pain (angina) Shortness of breath Fast heartbeat Shoulder or back pain Neck, jaw, or arm pain Sweating/clamminess Nausea/vomiting Fatigue Dizziness or light-headedness Myocardial infarction (heart attack)

Question 254

What are the main biomarkers for cardiac ischemia and why do we need more than one?

Answer 254

CK-MB (mass), Cardiac Troponins (I or T) and Myoglobin. More are in development. We need more than one marker as none of the markers we have are ideal, so a multiple approach give a more accurate picture of what is happening. Also, each of the markers are useful on different time scales allowing the diagnosis of an MI from 1 hr to 15 days

Question 255

What time frames do we see biomarkers appear after a myocardial infarction (heart attack) and how long are they a useful tool as a marker of a past cardiac event?

Answer 255

Myoglobin is released withing 1-4 hr but gone in 24hr CK-MB is released in 3-12 hr and is around for 2-3 days Troponin T is released from 4-12 hr and is around for up to 15 days

Question 256

What are free radicals? What can they do

Answer 256

Single unpaired electron in outer orbit Superoxide (O2-) hydroxyl radical (·OH) Normally generated during oxidative phosphorylation and Mopped up by antioxidants: e.g. vitamins A, C and E Or neutralised by enzymes e.g. catalase This is an increased problem when cellular homeostasis is lost (particularly when mitochondria are disrupted) Can result in lipid peroxidation and protein damage thus increasing cellular dysfunction

Question 257

Temporal aspect of cell damage

Answer 257

Ion leakage, metabolite accumulation, membrane rupture - macromolecules

Question 258

Describe the structure and function of smooth muscle

Answer 258

A single nucleus present in the central thick portion. Cytoplasm appears homogenous without striations. Fewer mitochondria as compared to the skeletal muscle. Metabolism mostly glycolytic. Actin, Myosin & Tropomyosin but NO Troponin Dense bodies serve the same purpose as the Z-discs Attached to the dense bodies are numerous numbers of Actin filaments Interspersed between the actin filaments are Myosin filaments In the walls of hollow organs, blood vessels, eye, glands, uterus, skin. Some functions: propel urine, mix food in digestive tract, dilating/constricting pupils, regulating blood flow, In some locations, autorhythmic Controlled involuntarily by endocrine and autonomic nervous systems

Question 259

Cardiac muscle structure and function

Answer 259

Striated, Actin and myosin, Epinephrine, Ca2+ from ECF and SR, Troponin as ca2+ regulatory protein, Gap junctions. Heart: major source of movement of blood Autorhythmic Controlled involuntarily by endocrine and autonomic nervous systems

Question 260

Skeletal muscle structure and function

Answer 260

Striated, Actin and myosin, No homrmonal contril, Ca2+ from SR, Troponin as ca2+ regulatory protein. Attached to bones Makes up 40% of body weight Responsible for locomotion, facial expressions, posture, respiratory movements, other types of body movement Voluntary in action; controlled by somatic motor neurons

Question 261

How is smooth muscle organised

Answer 261

Grouped into sheets in walls of hollow organs Longitudinal layer – muscle fibers run parallel to organ’s long axis Circular layer – muscle fibers run around circumference of the organ Both layers participate in peristalsis

Question 262

Single unit Smooth muscle

Answer 262

Muscles of visceral organs .e.g. GIT, uterus, ureters & some of the smaller blood vessels. Form a sheet or bundles of tissue. Cell membranes show gap junctions that allows AP to pass rapidly from cell to cell. AP spreads rapidly throughout the sheet of cells – cells contract as a single unit.

Question 263

Multi-unit smooth muscle

Answer 263

Iris & Ciliary body of the eye, large arteries, Piloerector muscles Showing discrete, individual smooth muscle fibers. Smooth muscle cells not electrically linked. Each muscle fiber innervated by a single nerve ending. NT itself can spread and lead to an AP. Selective activation of each muscle fiber that can then contract independently of each other.

Question 264

Smooth muscle contraction mechanism

Answer 264

Ca2+ binds calmodulin > Calmodulin binds myosin light chain kinase > MLCK phosphorylates light chain in myosin heads > ATPase activity increases > Actin slides along myosin to create tension.

Question 265

How does epinephrine work

Answer 265

Causes hyperpolarization which causes a reduced amount of cytosolic Ca2+ and thus relaxes the muscle cell

Question 266

Ach vs norepinephrine

Answer 266

ACh & norepinephrine are never secreted by the same nerve fiber ACh can be excitatory or inhibitory - determined by the type of receptor expressed by the target cell ACh and NE usually cause the opposite reaction at a target cell (If Ach is stimulatory then NE will most likely be inhibitory) Depending on the type of receptor norepinephrine and epinephrine can have different results on the smooth muscle cell Epinephrine bound to beta-adrenergic receptors on smooth muscle cells of the intestine causes them to relax Epinephrine also binds to the alpha2-adrenergic receptor found on smooth muscle cells lining the blood vessels in the intestinal tract, skin, and kidneys Epinephrine bound to alpha2 receptors causes the arteries to contract (constrict), reducing circulation to these organs

Question 267

Describe the relative nutritional value of the following nutrients: Carbohydrates, Proteins, Fats, Alcohol

Answer 267

More ATP comes from fat than alcohol than carbohydrate or protein

Question 268

Glycolysis

Answer 268

1 Glucose goes through a series of linked enzymatic reactions and is split into: 2 Pyruvate 4 ATP (but 2 were used) 2 NADH

Question 269

How is pyruvate turned into Acetyl CoA?

Answer 269

Transported into mitochondria Oxidatively decarboxylated to acetyl-CoA Pyruvate dehydrogenase (enzyme complex- 3 enzymes multiple copies) Irreversible reaction This reaction mainly takes place in tissues with high oxidative capacity- e.g. cardiac

Question 270

What is the TCA cycle?

Answer 270

For every 1 glucose (2 acetyl CoA) the cycle generates: 4 CO2 6 NADH 2 FADH2 2 ATP De na de na a fa na

Question 271

What is oxidative phosphorylation

Answer 271

The transfer of electrons from organic compounds through a series of electron carriers to O2 (or other inorganic or organic molecules (via oxidization)- keep in mind for free radicals) The transfer of electrons from one carrier to the next generates energy which is used to make ATP from ADP by chemiosmosis

Question 272

What has a higher energy yield? fat or glucose

Answer 272

Fat

Question 273

How is fat stored

Answer 273

As Triacylglycerols

Question 274

How is energy derived from fats?

Answer 274

Free Fatty acids converted to acetyl CoA for the TCA cycle. 131 ATP from whole process

Question 275

Why make glycogen?

Answer 275

Glycogen mobilized faster than fat 1% - 2% of mass in rested skeletal muscle Glycogen  Glucose-6-Phosphate G-6-P enters glycolytic pathway Glucose metabolism is both aerobic and anaerobic (in part) Fat metabolism is only aerobic Muscle lacks G-6-phosphatase Glucose cannot be exported Liver has G-6-phosphatase Glucose can be exported Liver provides body’s glucose

Question 276

What are ketone bodies?

Answer 276

During excessive fatty acid mobilisation: examples: b-oxidation, fasting, type I diabetes acetyl CoA production in liver is very high mitochondria oxidation of acetyl CoA cannot match production acetoacetate accumulates acetoacetate (~75%) is reduced to b-hydrobutyrate ketone bodies (acetoacetate, acetone & b-hydroxybutyrate) enter circulation ketone bodies can be used for energy in heart and brain (converted back to acetyl CoA)

Question 277

vDefinition of an Adverse Drug Reaction:

Answer 277

An unwanted or harmful reaction experienced following the administration of a drug or combination of drugs under normal conditions of use and which is suspected to be related to the drug

Question 278

ADRs: top five examples

Answer 278

NSAIDS (29.6%) e.g. aspirin, ibuprofen GI bleeding, CV haemorrhage, renal impairment Diuretics (27.3%) for high blood pressure Renal impairment, hypotension, electrolyte disturbance Warfarin (10.5%) To prevent clotting GI bleeding, haematuria, prolonged INR ACE-I/ARB (7.7%) for high blood pressure Renal impairment, hypotension, electrolyte disturbance Antidepressants (7.1%) Confusion, hypotension, constipation, hyponatraemia

Question 279

On target ADRs

Answer 279

Exaggeration of the drug’s normal effect E.g. excessive bleeding with warfarin Generally dose-dependent and can be reversed by lowering dose Why? Genetic factors Age Concurrent disease (esp liver or kidney disease)

Question 280

Off-target ADRs (4)

Answer 280

Idiosyncratic, not pharmacologically predictable e.g. allergic response to penicillins May be chronic - persisting for a relatively long time e.g. benzodiazepine dependence; analgesic nephropathy Delayed reactions - become apparent some time after the use of a medicine e.g. carcinogenic and teratogenic effects End of use reactions - Associated with withdrawal of a medicine e.g. insomnia, anxiety and perceptual disturbances following withdrawal of benzodiazepines such as midazolam

Question 281

Example of pharmacovigilance: (2)

Answer 281

UK Yellow Card scheme https://yellowcard.mhra.gov.uk/ Started in 1964 in response to thalidomide. Can lead to… Additional information in product leaflet Change in dosage Warnings to particular patient groups Withdrawal from market Black triangle scheme New medicines and vaccines that are under additional monitoring have an inverted black triangle symbol (▼) displayed in their package leaflet and in the British National Formulary (BNF) You should report all suspected ADRs for these products.

Question 282

Polar uncharged amino acids

Answer 282

Serine, Threonine, Cystine, Asparagine Glutamine, Tyrosine Santa’s Team Craft a giant toy Santa’s Team Crafts New Quilts Yearly

Question 283

Polar acidic amino acids

Answer 283

Aspartate, Glutamate Arctic glee Dragons Eat

Question 284

Polar basic amino acids

Answer 284

Lysine, Arginine, Histidine Lapland Arctic home Knights Riding Horses