ESA1 Mock Exam Qs Flashcards
Describe the metaplastic change that occurs in the airway epithelium of long term smokers
Mucus secreting pseudostratified ciliated columnar respiratory epithelial cells
To stratified squamous epithelium
What is the function of the mucociliary escalator
Waft/move mucus up airway via cilia to throat, in order to be swallowed
Works as a barrier to infection
What is the most likely gram positive organism to cause chest infection
Streptococcus pneumonia
Describe the process of gram staining
Cells stained with crystal violet dye
Iodine added & forms large molecular complex with crystal violet
Acetone or methanol added; acts as a decolorizer
Crystal violet trapped by thick peptidoglycan layer of gram +ve bacteria
Acetone/methanol degrades thinner peptidoglycan layer of gram -ve bacteria, so decolourizes it
Red dye (safranin) used to stain bacteria (unstained gram -ve cell) red
A 27 year old female with appendicitis is placed under general anaesthetic. Her heart rate & temperature begin to increase, as does her pO2
What do you suspect has happened?
Her muscles also become rigid. What drug would you administer to correct this & what is the mechanism of action
Malignant hyperthermia
Dantrolene: a muscle relaxant preventing calcium release
What enzyme is inhibited by the action of penicillin
Transpeptidase
Involved in formation of peptidoglycan cross-links in bacterial cell wall. No cross linking means bacterial cell dies
Explain the pathophysiology of rigor mortis
No respiration results in no ATP being produced
Actin-myosin complex remains unbroken
Muscles remain contracted
What are the layers of the meninges, starting from outermost layer
Dura mater
Arachnoid mater
Pia mater
Name the cells responsible for myelination in the CNS
Oligodendrocytes
Explain how anti-pyretic drugs work
Inhibit cyclo-oxegenase enzyme
Reduce levels of prostaglandins (PGE2) within the hypothalamus
How do you work out incidence rate
How do you work out incidence rate per X number of people
No of new events / no of people x time (yrs)
IR x no of years
Outline the process of fracture (long bone) healing
Haematoma formation
Fibrocartilage callus formation
Bony callus formation: calcified to secondary bone
Bone remodelling
Explain how the body keeps calcium levels constant, with respect to bone
Parathyroid gland senses low free calcium
This stimulates PTH secretion
PTH increases serum calcium by stimulating oesteoclast activity
(PTH also increases activity of enzyme creating active form of Vit D)
What is a keloid?
Excessive scarring on the skin caused by abnormal amounts of collagen
Usually occurs at sites of surgical incision or trauma
What types of immune cells would you expect to see at the site of a wound and what are their respective functions?
Neutrophil: phagocytosis
Monocyte/macrophage: phagocytosis, remove cell debris
Basophils: mediate acute inflammatory reactions, using heparin & histamine
B lymphocytes: make antibodies against antigens
T lymphocytes: assist other WBCs (helper) / destroy virus-infected cells (killer)
What are the functions of the skin
Barrier to infection Psychosexual communication Sensory Thermoregulation Produce Vit D Control of evaporation Barrier against mechanical/thermal/physical injury
Outline the process of renewal of the epidermis
Keratinocytes multiply (mitosis) in stratum basale & move up to stratum spinosu
Keratinocytes undergo apoptosis in stratum granulosum & loose nucleus
Keratinocytes terminally differentiated by time stratum corneum
Dead cells shed from stratum corneum
Outline the steps of collagen synthesis
Synthesis & entry of chain into RER
cleavage of signal peptide (by signal peptidase)
Hydroxylation of selected proline & lysine residues (by prolyl hydroxylase, which requires Vit C + Fe2+)
Addition of N linked oligosaccharides + galactose to hydroxylysine residues
Chain alignment, formation of disulphide bonds (by disulphide isomerase)
Formation of triple helical procollagen from C to N terminus
Completion of O linked oligosaccharide chains by addition of glucose
Transported in vesicle & released by exocytosis
Removal of N & C terminal peptidase (by procollagen peptidase)
Forms tropocollagen
Covalent cross linking & aggregation of fibrils by lysyl hydroxylase
Describe the structure of myoglobin & haemoglobin
Mb:
Single subunit protein that contains one Harm grp for binding & transport of oxygen
Can bind one molecule of oxygen
Hyperbolic O2 binding: no cooperativity
Hb:
Tetrameric protein (2 alpha, 2 beta subunits), containing 4 Haem grps
Can bind 4 molecules of oxygen
Sigmoidal O2 binding. Cooperative binding
Describe the effects of 2,3 BPG on binding of oxygen on Hb & the physiological significance of this
Decreases affinity of Hb for O2
Curve shifts to the right
BPG conc increases at high altitudes, promoting O2 release at tissues
BOG also produced during metabolism, so O2 released more readily in areas performing high amts of metabolism
Describe the structural differences between oxygen & deoxygenated Hb
Oxygenated:
Binding of O2 promotes stabilisation of R state, which allows for cooperativity
Deoxygenated:
Can exist in low affinity T state
Describe the pathophysiology of sickle cell anaemia
In deoxygenated state, rbc’s take up sickle shape & polymerise
When oxygenated, rbc’s return to normal biconcave shape
Repeated cycle of deoxygenation & oxygenation = rbc looses elasticity
Stays in sickled state
Unable to pass thru narrow capillaries, causing occlusion & Ischaemia
Shape also predisposes cell to early destruction by haemolysis (30 days rather than 120)
Causes anaemia
Why can cole weather, being ill & being dehydrated make sickle cell disease worse?
Cold: causes vasoconstriction, passage of already distorted rbc’s more difficult & ore prone to lysis
Dehydration: contraction of extracellular vol, increases blood viscosity, increases likelihood of vaso-occlusive crisis
Ill: increases no of WBCs, which increases viscosity of blood. Makes it difficult for rbc’s to pass thru capillaries
Sickle cell disease = functionally asplenic
Less able to fight off bacteria & risk of being overwhelmed by infection
What is a sickle cell crisis?
Lack of perfusion to an area causing ischaemic injury & subsequent pain
Describe the process of DNA replication
Initiation:
Recognition of / binding to an ‘origin of replication’
DNA helicase unravels DNA double helix
RNA primase lays down primers
Elongation:
Replication from 5’ to 3’ in both leading & lagging strands
Lagging strand replaced discontinuously (Okazaki fragments)
Termination:
RNA primers removed
Discontinuous fragments joined up by DNA ligase
Semi conservative replication:
2 daughter helices have 1 strand comprised of parental DNA from original & one newly synthesised strand
Describe DNA gel electrophoresis
Used to separate diff sized DNA fragments:
Agarose gel submersed in tank of buffer solution (conducts electricity)
DNA fragments added to agarose gel
Dye added for better visualisation of DNA
DNA negatively charged & moves to positive electrode when electric current present
Larger fragments move slower
Fragments of known size used as a reference
Explain PCR & describe its uses
Amplified DNA segments by repeated copying of target DNA using thermo-stable DNA polymerase & pair of primers that uniquely define region to be copied
Denaturation: high temp (94-96)
Double stranded DNA becomes single stranded
Annealing: lower temp (50-65)
Primers bind to strands
Renaturation/DNA synthesis: medium temp (75-80)
DNA Taq polymerase synthesises complementary DNA strand
Used to:
Amplify specific DNA fragment
Investigate single base mutations
State the 3 layers of the adrenal cortex & their respective secretions
Zona reticularis: androgens, cortisol
Zona fasciculata: glucocorticoids
Zona glomerulosa: mineralocorticoids
Why is a patient with Addisons hypotensive?
Aldosterone stimulates reabsorption of sodium and hence water
Therefore no aldosterone = less water retention by kidneys = hypovolemia, hypotension
Why is an Addisonian patient’s skin pigmented?
Adrenal gland dysfunction = low cortisol
Negative feedback = more ACTH released from pituitary gland
ACTH & MSH both derived from POMC
MSH stimulates melanocytes to produce melanin, therefore skin pigmentation
If a patient is suffering with Addisons, what would the Synacthen test show & why
Low cortisol/doesnt rise above 540 nmol/l
Despite admin of synthetic ACTH
suggesting primary adrenal insufficiency
What would the blood test of a patient with Graves disease show & why
High T3 & T4: autoantibodies stimulate TSH receptors
Low TSH: negative feedback from high T3/T4, to reduce TSH production
Describe the steps involved in synthesis of T3 & T4
Stimulated by TSH
thyroglobulin synthesis in thyroid epithelial cells
Exocytosis of thyroglobulin into colloid
Iodination of tyrosine residues on thyroglobulin
Coupling of 2 x DIT to make T4 & MIT + DIT to make T3
Endocytosis of iodinated thyroglobulin into follicular cell
Proteolytic Cleavage to make free T3/T4
Diffuse from epithelial cells & Exocytosis into bloodstream
Explain the mechanism of action of Carbimazole & what it is used for
To treat hyperthyroidism
Metabolised to methionine
Inhibits thyroid peroxidase
Prevents iodination of tyrosine residues
Explain the mechanism by which alcohol causes:
Jaindice
Ascites
Hepatomegaly
Jaundice:
Mixed myoerbilirubinaemia from mixture of hepatocellular injury & cholestasis
Ascites:
Reduced protein synthesis e.g. Albumin in damaged liver = reduced oncotic pressure in blood vessels. Hydrostatic pressure greater than oncotic pressure which favours mvmt of fluid out into intestinal space
Also Liver cirrhosis = portal htn
Hepatomegaly:
Lipid deposition in liver (alcoholic fatty liver disease) = hepatomegaly
What is the mechanism of Disulfiram
Inhibitor of aldehyde dehydrogenase
Causes build up of acetaldehyde
This is a toxic metabolite causing unpleasant hangover-type symptoms
Why would a patient with alcoholic liver disease display extensive bruising & bleeding
Clotting factors are synthesised by liver
Liver damage = reduced synthesis of clotting factors
Malnutrition also common in alcoholics, may = vit K deficiency
What causes the sweet smelling breath of someone in Diabetic kKetoacidosis
Absolute lack of insulin
Causes production & build up of ketones in blood
Acetone is one type of ketone & causes acetone smell on breath
State the features of an alpha helix & beta sheet
Alpha helix:
Right handed helix
3.6 aa per turn
0.54nm pitch
Beta sheet:
Extended conformation
Parallel or antiparallel
Multiple inter-strand H bonds
What are apolipoproteins & describe their role in lipid transport
They bind to lipids to form lipoproteins
Lipids are insoluble in water
Lipoprotein molecules allow for molecule to be transported in aqueous env
Interact with receptors & enzymes so that lipids can be taken up by cells
What is the underlying genetic defect in familial hypercholesterolaemia & explain what the blood test results would be
What conditions would a patient be at risk of
Defective LDL receptors
Reduced LDLs uptake by hepatocytes
= increased levels of circulation LDLs
CAD/MI
stroke
Peripheral vascular disease
Explain the following:
95% CI for age & deprivation adjusted IRR for female south asians compared with female non-south asians for all cancers is 0.49-0.79
Why might incidence increase over time amongst SAs?
The 95% CI doesnt contain 1 The null hyp can be rejected (p<0.05) Unlikely to be due to chance Stat sig finding IR of cancers in FSA less than IR of cancer in FNSA
Lifestyle factors e.g. Changes in diet
At which stage if the cell cycle do chromosomes replicate?
Synthesis (S)
What study would you use to investigate:
Incidence of rare chronic granulamatous disease in people vaccinated against measles as a baby
Case control
Good for rare diseases
Likelihood of dev condition is low, so cant use cohort
What would be seen on an endocrine test for Addisons
Hyponatremia ( from lack of aldosterone ) hyperkalaemia (from lack of aldosterone), hypoglycaemia (from lack of cortisol)
Which classification do salivary glands belong?
Compound tubuloalveloar
What is the pattern of inheritance of Becker’s Muscular Dystrophy
X linked recessive
What is the diagnostic value for diabetes in HBA1C
> 10 % (normal 4-6%)
What antigen is found in hyperthyroidism (Grave’s disease)
Anti-thyroid peroxidase antibodies (anti-TPO)
Thyrotrophin receptor antibodies (TRA bs)
Thyroglobulin antibodies
What is the lifespan of a red blood cell
110-120 days
Outline the mechanisms of erythropoeisis
Controlled by partial pressure of O2
pO2 stimulates erythropoietin
Feedback system:
Increased production of erythropoietin from peritubular endothelial cells (kidney) in response to hypoxia
Erythropoietin increases rate of rbc production & release from bone marrow
Increased oxygen carrying capacity of blood
Describe the affect of Hb dissociation curve at high altitudes
HB increases at high altitudes Reduced affinity of Hb for O2 Curve shifts to the right Tense state Less taken up by lungs More released at tissues
Similar to increased 2,3 BPG
Describe coeliac disease
Explain why patients have a higher risk of fractures
Mainly affects small intestine: inflammation
Reaction to gluten
Autoimmune
Destroys villi
Vitamin D deficiency = orsteomalacia
Oesteoporosis
What are the chemical bonds found in glucogen
Alpha 1,4 glycosidic bonds: link main stem glucose molecules
Alpha 1,6 glycosidic bonds: link stem & branch
Cellulose:
Describe its function in the GIT
describe its chemical structure
Hydrophilic bulking agent for faeces: dietary fibre
Beta 1,4 linked glucose units
Straight chain polymer
Humans don’t have enzymes to digest these bonds
Describe the allosteric regulation of enzymes
Regulation of a protein (multisubunit enzyme) by binding effector molecule at a site other than protein’s (enzyme’s) active site
More than one active site for substrate
In the endocrine pancreas:
what 3 types of cells are found
What do they secrete
Where are they found
In the exocrine pancreas:
What types of cells are found
What do they secrete
What are they stimulated by
Endocrine:
In islets of langerhans
Alpha cells: glucagon (increase blood glucose)
Beta cells: insulin (decrease blood glucose)
Delta cells: somatostatin (regulates/stops alpha & beta cells)
Gamma cells: pancreatic polypeptide
Exocrine:
Ducts containing acini
Proteases (trypsinogen, chymotrypsinogen), lipases, amylases, bicarbonate ions
Secretin, gastrin, CCK
Describe Nissel body/substance
Where it is found
What it contains
large granular body found in neurons
granules are RER with rosettes of free ribosomes
are the site of protein synthesis
What are the classifications of muscle & describe their features
Skeletal: Striated Multinucleated; at periphery Cells cant divide: regenerate by mitotic activity of satellite cells; increases musc mass Gross damaged repaired by CT (scar) T tubules in line with A/I band
Cardiac:
Striated
1-2 nuclei per cell; central
Branched
Incapable of regeneration: fibroblasts invade & lay down scar tissue
T tubules in line with Z bands
Intercalated discs: Gap junctions (electrical coupling), adherens type junctions (anchor cells) desmosomes
purkinje fibres (modified monocytes with extensive gap junctions: rapid direction of AP so ventricles contract in synch)
Smooth: Not striated Single nucleus; central Spindle shaped (fusiform) Cells retain mitotic activity; can form new smooth musc
Define connective tissue
Tissues of mesodermal origin containing:
Cells
Ground substance
Extracellular fibres
Support organs
Fill spaces between organs
Form tendons & ligaments
Outline the types of connective tissue
Loose: e.g. Blood, adipose tissue, areolar tissue, reticular tissue
Dense regular: e.g. Tendons, ligaments, aponeuroses
Regular irregular: e.g. Dermis, periosteum, perichondrium, dura mater
Outline the types of cartilage & where they are found
Type of collagen contained in each
Hyaline (type 2 collagen): e.g. Articulating surfaces of long bones, anterior ends of ribs, respiratory passageways, foetal skeleton
Elastic (type 2 collagen): e.g. Pinna, eustachian tube, epiglottis
Fibrocartilage (bundles of type 1 collagen): e.g. Intervertebral discs, knee menisci, pubic symphysis, temperomandibular joint
Describe portal systemic anastamoses
specific type of anastomosis that occurs between the veins of portal circulation and those of systemic circulation.
Areas (& vessels involved):
Oesophageal (oesophageal branches of azygous vein)
Rectal (middle & inferior rectal veins)
Paraumbilical (superficial epigastric vein)
Retroperitoneal (renal, suprarenal, paravertebral, gonadal vein)
Intra hepatic (inferior vena cava)
Describe portal hypertension
Causes
Symptoms
high blood pressure in the portal vein system, which is composed of the portal vein, and its branches and tributaries.
Consequences of portal hypertension are caused by blood being forced down alternate channels by the increased resistance to flow through the systemic venous system rather than the portal system.
Prehepatic causes: portal vein thrombosis or congenital atresia.
Intrahepatic causes: liver cirrhosis, hepatic fibrosis
Posthepatic obstruction: at any level between liver and right heart, including hepatic vein thrombosis, inferior vena cava thrombosis, inferior vena cava congenital malformation, and constrictive pericarditis.
Ascites
Hepatic encephalopathy.
Increased risk of spontaneous bacterial peritonitis.
Increased risk of hepatorenal syndrome.
Splenomegaly
Portal systemic anastomoses: Esophageal varices, gastric varices, anorectal varices (not to be confused with hemorrhoids), and caput medusae. Esophageal and gastric varices pose an ongoing risk of life-threatening hemorrhage, with hematemesis or melena.
Describe how glycogen enters the main glycolysis pathway
Glycogenolysis occurs in liver & skeletal muscles
Glycogen broken down by glycogen phosphorylase & debranching emzyme
Produces glucose 1 P
This is acted on by phosphoglucomutase to produce glucose 6 P
This is acted on by glucose 6 phosphatase in the liver to produce glucose
What is the result of chronic persistent hyperglycaemia in the plasma?
Aldose reductase converts glucose to sorbitol
Depletes NADPH
Non-enzymatic glycosylation = loss of structure & function of plasma protein
Outline the formation of a mature insulin molecule
Synthesised as inactive single polypeptide chain = preproinsulin
Removal of signal peptide (signal peptidase)
3 disulphide bonds formed = proinsulin
Removal of C peptide (endopeptidase) = mature insulin molecule
How are the disaccharides & dextrins digested?
Name 3’enzymes that digest here
Digestion occurs in duodenum & jejunum
Releases monosaccharides: glucose, fructose, galactose
Glycosidase enzymes: large glycoprotein compkexes attached to brush border of membranes of epithelial cells
E.g. Lacatse, glycoamylase, sucrase
Why would someone with lactose intolerance suffer from cataracts if they have a high lactose diet?
Accumulation of galactose in tissues Reduction to galactitol Depletes tissues of NADPH Free SH grps cant be maintained Lens proteins in eye cross linked by disulphide bonds = cataracts
How can NADPH be used as a first defence mechanism in cells?
A reducing agent
Converts glutathione disulphide (GSSG) back to glutathione (GSH) in cells
Glutathione acts as reducing agent to neutralise ROS in cells
What is the purpose of phase 1 & phase 2 drug metabolism
Phase 1: add/expose a reactive group on a drug
Phase 2: conjugation - add sulphate, glucuronic acid, glutathione
Explain why an overdose of paracetamol can be deadly & give ghe treatment of an overdose
Saturates both glucoronic & sulphate pathways of usual phase 2 metabolism
Phase 1 metabolism produces toxic compound NAPQI
NAPQI undergoes phase 2 metabolism, conjugating with glutathione
Removes liver cell’s primary antioxidant, leaving them prone to oxidative stress by ROS: can cause liver damage
N-acetyl cysteine
Describe how the healthy worker effect leads to bias
Use of workers in studies as a representative of the entire population may lead to bias as workers are generally in good health as they are able to work
Why does vitamin C result in weakened structures that contain collagen
Is a cofactor needed by enzyme prolyl hydroxylase for hydroxylation of proline residues
Lack of vitamin C = weakened tropocollagen helixes
Outline elongation of mRNA translation
Met-tRNA occupies P site on ribosome
Empty A site allows binding of other amino-acyl-tRNA (An energy requiring reaction)
Complementary anti-codon for codon on mRNA
Peptide bond forms between 2 amino acids via peptidyl transferase
tRNA at P site now uncharged & leaves
Ribosome undergoes translocation (requires energy)
Moves towards mRNA 3’ end, exposing another empty a site
Collagen is a main component of connective tissue.
What are the differences in arrangement of collagen fibres in dense regular & dense irregular connective tissue?
How does the difference in arrangement explain the difference in function of the two?
Dense regular: collagen packed tightly in parallel, unidirectionally
Max tensile strength, for unidirectional forces
Dense irregular: interwoven bundles packed multidimentionally
Can withstand multidirectional forces, to prevent tearing
What is the role of mast cells?
Found near blood vessels
Involved in allergic & hypersensitivity reactions
Contain granules of:
Histamine (increase permeability of blood vessel walls)
Heparin (coagulation)
What are the products of POMC cleavage?
ACTH
Alpha-MSH
Beta-endorphin
What does the Barker Hypothesis state?
Experience of the foetus in utero during development determines future health if the individual
How are zymogens activated
Removal of part of the polypeptide chain (proteolytic cleavage)
How is cortisol secretion controlled?
Negative feedback by levels of cortisol in the blood
Hypothalamus secretes CRH
Pituitary stimulated & secreted ACTH
ACTH stimulates adrenal glands to produce cortisol
Outline the process of endochondral ossification from the embryo to the mature adult
Mineralisation if hyaline cartilage:
Embryonic:
collar if periosteal bone forms
Central cartilage in the diaphysis calcifies
Primary ossification centre forms in diaphysis
Postnatal:
Medulla becomes cancellous bone
Cartilage forms epiphyseal growth plates
Secondary ossification centres from in epiphyses
Prepubertal:
Growth of bond by interstitial & appositional growth at the epiphyseal growth plates - ossification of epiphyses
Mature adult:
Ossification if epiphyseal growth plate - stop growth
Hyaline cartilage remains at articulating surfaces
(Periosteum only at non-articulating surfaces)
What conditions cause normal long bone development to be impaired & why?
Pituitary dwarfism:
Lack of growth hormone affects epiphyseal growth plates
Gigantism:
Excess growth hormone (before calcification of epiphyseal growth plates) = extensive endochondral ossification
Acromegaly:
Excess growth hormone (after calcification of epiphyseal growth plate) = excessive intramembranous ossification = large face/jaw, broad features
Achondroplasia:
Failure if proliferation of column formation of epiphyseal cartilage = impaired long bone growth = short limbs (normal trunk)
Rickets:
Lack of calcium/Vitamin D = poor calcification of bone = sift, malformed (epiphyseal plates distorted by body weight)
Oesteogenesis imperfecta:
Defect in collagen = weak bones prone to fracture = deformed bones
Describe if & how each muscle type regenerates
Skeletal: regenerates vis satellite cells
Cardiac: cant regenerate
Smooth: can regenerate
What is the difference in function between myoepithelial cells & myofibrils?
Myoepithelia:
Assist secretion of some exocrine glands
Myofibrils:
Secrete collagen at sites of wound healing/contract to bring edges together
Damage to a piece of DNA has occurred via deamination of a base.
How is this repaired?
Base excision repair
Faulty base removed by enzymes & replaced by correct one
Why is build up of phenylpyruvate in PKU a problem?
Inhibits uptake of pyruvate into mitochondria
Glucose isn’t metabolised as effectively
Can lead to brain damage
(brain highly dependent on glucose metabolism to function)
What is the function of hormone sensitive lipase & how is it regulated
Controls release of fatty acids from adipose tissue
Phosphorylated = activated by glucagon & adrenaline
Dephosphorylated = inhibited by insulin
How is erythropoiesis controlled?
Interstitial peri tubular cells of kidney detect low pO2 (hypoxia)
Increase production of erythropoietin
Stimulates production of rbc’s, increasing tissue oxygenation
Kidney detects tissue oxygenation & reduced production of erythropoietin
Around what day does compaction occur & what does it produce?
Day 4
Trophoblast & inner cell mass (embryoblast)
What is the difference between pharmacodynamics & pharmacokinetics
Dynamics = what drug does to the body
Kinetics = what body does to the drug
Why might someone with type 1 diabetes get blurred vision?
Insulin deficiency = high plasma conc of glucose
Uptake of glucose by eyes dependent on surrounding conc of glucose (not insulin)
Therefore lots of glucose taken up by eyes, giving blurred vision
What are 2 functions of platelets
Prevent blood loss
Adhere to damaged cell walls by aggregating together
Name the types of white blood cells & what they do
& shape of nucleus
Basophils
Neutrophils: phagocytosis, migrate to site of infection (multilobed)
Monocytes: become macrophages, phagocytosis (kidney shaped)
Eosinophils: phagocytosis, release cytotoxic particles (bilobed)
T lymphocytes: helper/killer - express CD4 receptor (deep staining)
B lymphocytes: humoral immunity, secrete Ig, stimulated by antigens
Describe the histology of the thyroid gland
Follicular cells contain thyroglobulin colloid
Follicle surrounded by simple cuboidal or columnar epithelia
C cells darkly stained & found in epithelia
What parts of the cell does haematoxylin stain purple
What part of the cell does Eiosin stain pink
Acidic components (e.g. Nucleus, chromatin)
Basic components (e.g. Cytoplasmic proteins, extracellular fibres)
Outline the synthesis of T3 & T4
Transport of iodine into epithelia (against conc gradient)
Thyroglobulin (tyrosine rich protein) secreted by exocytosis into lumen
Iodination of tyrosine side groups forms MIT or DIT
DIT + MIT = T3
DIT + DIT = T4
Explain the process of DNA sequencing using the Sanger method
Radioactively stained ddNTPs added to template strand with DNA polymerase
Depending on which ddNTP used, strand will terminate at diff places
Produces lots of DNA fragments if diff lengths that can be denatured with heat & separated with gel electrophoresis
How is Myasthenia Gravis treated?
Acetylcholinesterase inhibitors (e.g. Neostigmine)
What is non-disjunction between chromosomes
Failure of homologous pairs to split in meiosis
can lead to extra chromosome (e.g. Trisomy 21)
Distinguish between these different types of microscopy: Phase contrast Dark field Fluorescence Confocal
What are they?
What are the useful for?
PC:
Interference of 2 combining light waves
Enhancing image of unstained cells
DF:
Exclude unscattered beam from image
Live/unstained samples
Fl:
Molecule targeted with Fluorescent antibodies
Multiple fluorescent stains for one sample
Con:
Tissue labelled with fluorescent probes
Eliminates out of focus flare/produce 3D image/ living specimens
Why is blood considered to be a connective tissue?
Has fluid/semi fluid matrix
Contains fibres (soluble, un-clotted blood)
Derived from mesoderm
What two properties of heamoglobins enable them to be separated by electrophoresis
Net charge
Size
What possible molecular explanations are there for the presence of abnormal heamoglobins in the patients blood
Production of structurally abnormal Hb molecules due to mutation in globin structural gene
Presence of abnormal ration of subunits due to over or under production of globin subunits
Change in post-translational modification of globin sub-units
What is anaemia?
Why would is patient suffering from anaemia likely to feel tired?
Lower than normal conc of Hb in the blood
Low Hb associated with reduced ability to carry oxygen to tissues
Reduced aerobic metabolism
Inadequate ATP level yo maintain cell function
What does a crude mortality rate ratio of 2 indicate for A compared to B
A has twice the rate of deaths than B
If a crude mortality rate ratio is found to be 2 for A compared to B:
What characteristics of the populations would you like to know before accepting A is more deadly than B?
How would this explain the mortality rate ratio?
Age distribution of the populations
Age distribution may be acting ad a confounder
If A has more elderly population than B, & elderly people more likely to die, then A may have a higher mortality rate than B because of its more elderly population
What visualisation techniques may be used to investigate rectal bleeding from suspected cancer
Endoscopy/ sigmoidoscopy/ colonoscopy with poss biopsy
Barium enema
What macroscopic features of rectal cancer leads to bleeding
Ulceration
Raised/ stenotic/ fungating/ invading wall
State the epithelia of the large intestine & anal canal
Large intestine = simple columnar (non-ciliated)
Anal canal = stratified squamous, keratinized
From which embryonic tissue does the mucosa of the gut arise?
Endoderm
What components, other than epithelium, are included in the intestinal mucosa
Lamina propria
Smooth muscle / muscularis mucosa
Describe TNM staging for cancer
Describe Duke’s staging for bowel cance
TNM:
T = tumour. size of the original (primary) tumor & whether invaded nearby tissue,
N =node. nearby (regional) lymph nodes involved,
M =metastasis (spread of cancer from one part of the body to another).
Duke's: A = confined to bowel wall B = thru muscle wall, lymph nodes clear C = lymph node involvement C1/C2 = highest node clear/involved
What enzyme is usually measured in the blood in order to establish diagnosis of acute pancreatitis
Serum amylase
What are the common precipitating (causes/triggers onset) factors to the development of acute pancreatitis
Galls stones
Alcohol
Hypothermia
Various drugs
Why might blood glucose be elevated in someone with pancreatitis
Destruction of Islets of Langerhans leading to diabetes
What are the strengths & weaknesses of a case control study
Strengths: Quick Inexpensive Good for rare diseases Range of exposures can be studied for one disease No concerns with loss to follow up
Weaknesses:
More prone to information bias (e.g. Recall bias)
More prone to selection bias (therefore choice of controls crucial)
Nt good for rare exposures
Cant necessarily establish exposure preceded onset of disease
Cant directly measure incidence
What happens to carbohydrate eaten in excess lf the body’s immediate requirement for energy?
Stored as glycogen in the liver & skeletal muscle
Converted to fatty acids & stored as TAGs in adipose tissue
What are the histological features of an adipocyte from white adipose tissue
Large lipid droplet (TAG) filling the cell
Nucleus pushed to one side
Small amount of cytoplasm pushed to one side
Small number of mitochondria
How are fatty acids transported in the blood?
Why does the conc of FAs in the blood never increase much above 3mM
Hydrophobic & can only be transported bound to albumin
Albumin only has limited capacity to bind FAs as binding specific & is a limit to amount of fatty acids that can be in circulation in any one time
Describe some limitations of the cognitive models such as the health belief model
Social & env influences reduced to cognitions
Don’t account for how beliefs/attitudes may change over time
Dont incl emotional components involved
Assume people define risk on rational manner
People may not act rationally
Act out of habit, & not as result of decision
Outcomes may be perceived/valued differently; what is rational to one person may not be for another
Which of the following statements best describes the mechanism of action of the antibiotic chloramphenicol?
A Inhibits bacterial protein synthesis B Inhibits bacterial RNA polymerase C Inhibits DNA polymerase D Inhibits mammalian protein synthesis E Inhibits mammalian RNA polymerase
A
Which of the following intermediates of collagen biosynthesis will signal peptidase act upon?
A Collagen fibre B Collagen fibril C Preprocollagen D Procollagen E Tropocollagen
C
A mutation is found to have occurred in the last intron-exon boundary of a gene. What is likely to be the first process to be affected by this mutation?
A Polyadenylation B RNA capping C Splicing D Transcription initiation E Transcription termination
C
Which of the following are cells of the innate and adaptive immune system, respectively, responsible for the destruction of virally infected cells?
A B lymphocytes and eosinophils
B Cytotoxic T lymphocytes and neutrophils
C Helper T lymphocytes and eosinophils
D Natural killer cells and cytotoxic T lymphocytes
E Macrophages and helper T lymphocytes
D
When a study is double-blinded, the potential for which types of bias is reduced?
A. Healthy worker effect and selection bias
B. Placebo effect and observer bias
C. Placebo effect and measurement bias
D. Selection bias and observer bias
E. Observer bias and differential misclassification
B
What is pK
What is the equation for pK
Extent to which acid dissociates (strength of an acid)
pK = -log [Ka]
What is the Henderson Hasselbach equation
What is it useful for
pH = pKa + log ([A][HA])
A = conjugate base HA = acid
Estimating buffer solution
Equilibrium of pH in acid-base reactions
(pI of some proteins)
Describe the key features of amino acid metabolism
Constant turnover of proteins (making/breaking) makes free aa’s
Can be used to make other proteins
Rich diet = excess aa’s
Liver disposes of excess aa’s
Prob: amine group potentially toxic (transamination or deamination)
Enzymes remove NH2 grp leaving C skeleton, with 2 poss pathways:
Ketogenic aa’s (e.g. Leucine, lysine):
used to make ketone bodies from acetyl CoA
Glucogenic aa’s (e.g. Glutamate, glutamine):
can make glucose (glucoenogenesis)
Some aa’s are both ketogenic & glucogenic:
(e.g. Isoleucine, penylalanine, tyrosine)
Describe transamination
Transfer of amino group to a keto-acid
Uses alpha ketoglutarate or oxaloacetate (TCA intermediates)
Converts range of aa’s to glutamate or aspartate: useful products
(Can feed into urea cycle)
aa + alpha-ketoglutarate -> glutamate + keto acid
aa + oxaloacetate > aspartate + keto acid
Process is reversible
Describe deamination
Disposal of amine group (NH2)
Removed from amino acid to form ammonia (NH3)
Converted to ammonium ion (NH4+)
These are very toxic (esp to neurones) & must be removed/converted to non-toxic products:
Glutamate -> aspartate -> urea cycle -> urea (water soluble)
(Ammonia + aspartate -> urea)
(Urea cycle can be up/down regulated)
Glutamate -> glutamine (good store / transport for ammonia)
Describe the process of ammonia detoxification
Initially NH3 used to synthesise glutamine
Then NH3 (released from glutamine) either excreted directly or converted to urea
Describe the synthesis of glutamine
Made from Glutamate + ammonia in cells (requires ATP)
Used to Synthesise N compounds (e.g. Purines, pyrimidines)
Excess released from cells, transported in blood to liver & kidney, where broken down to release ammonia (glutaminase)
Kidney: ammonia excreted directly in urine
Liver: ammonia used to make urea
Describe visceral vs parietal pain
Peritoneal cavity made of visceral & parietal peritoneum
But these dev from diff embryological pathways:
Viscera (e.g surrounding intraperitoneal structures) don’t have somatic nerve supply
When viscera stretched/irritated chemically etc, pain will be referred according to whether that structured belonged to foregut (epigastric) midgut (periumbilical), or hindgut (suprapubic)
Follow splanchnic nerves that exit at dermatome of these central areas
Visceral peritoneum therefore refers pain along the midline
Parietal peritoneum lines the body wall: has more dedicated somatic innervation and therefore is more localised
Describe the boundaries of the inguinal canal
Floor = inguinal ligament (lacunar ligament medially)
Roof = internal oblique / transverse abdominus (musc arches & aponeurosis)
Posterior wall = transversalis fascia (innermost layer; includes conjoint tendon medially)
Anterior wall = aponeurosis of external oblique
What pouched/recesses exist in the peritoneal cavity
Whats their clinical significance
Pouch of Morrison/hepatorenal recess/subphrenic recess:
Separates liver & right kidney (behind duodenum)
Pouch of Douglas/rectouterine pouch (females):
Between rectum & posterior wall of uterus
Vesico-uterine pouch (uterovesical pouch of Meiring) (females):
Between Uterus, bladder, part of intestinal surface (shallower)
Rectovesicle pouch (males): Reflects onto posterior wall of bladder
Paracolic gutters:
Between ascending/descending colon & abdominal wall on either side
Are potential spaces that can collect fluid/infection which can then travel around peritoneal cavity
(Often when lying down)
In embryological terms, whats the falciform ligament a remnant of
The Falciform ligament is a remnant of the Ventral mesogastrium of the foregut
The Liver develops in this mesentery dividing it up into the Falciform ligament (Anterior wall- Liver) Lesser Omentum (Liver-Stomach
Describe what the following tests show: ALT ALP AST Albumin Bilirubin
Alanine transaminase (ALT) is specific to hepatocytes and so if they are damaged it is released into plasma.
ALP tends to rise in biliary obstruction and bone disease.
AST is raised in liver damage but is also present in reasonable quantities in cardiac and skeletal muscle and so is not
that specific to the liver.
The healthy liver produces albumin so hepatocyte damage will not result in more albumin
Raised conjugated Bilirubin levels is seen more in Biliary obstruction that occurs after conjugation has occurred
(common bile duct blockage etc).
What differences are there in the abdominal wall above & below the arcuate line (line of Douglas)
The Rectus muscles are surrounded by the aponeurosis of the other abdominal wall muscles;
- both anterior and posterior to them above the arcuate line
- only anterior below it below the arcuate line
Explain the origin of the pmf at the inner mitochondrial membrane
Three of the enzyme complexes in the electron transport chain also
act as proton translocating complexes (pumps).
These complexes use energy from the electron transport chain to
pump protons from the inside to the outside of the membrane.
The membrane is impermeable to protons and therefore an
electrochemical gradient is established across the membrane.
How is ATP produced at the inner mitochondrial membrane
Energy from the proton motive force is used to drive the production
of ATP by ATP synthase enzyme.
Explain why the pancreas may become diseased in someone with CF
The CFTR ion channel is absent.
As a result, chloride ion transport out of the exocrine tissue is
substantially compromised.
Consequently, water does not leave the epithelium in sufficient
quantities to adequately hydrate the secretions.
The secretions therefore contain too little water and become
thickened/viscous, with resultant blocking of the ducts.
Name some general mechanisms that can be used to regulate enzyme activity
Proteolytic cleavage Vary substrate concentration. Allosteric effectors. Product inhibition. Phosphorylation/dephosphorylation. Binding to a regulatory protein. Sequester enzyme/substrate in an organelle. Proteolytic degradation (via ubiquitination). Change rate of transcription. Change rate of translation.
How is trypsin formed from trypsinogen?
Why is trypsin initially produced as trypsinogen?
How is any premature activation of trypsin in the pancreas
dealt with?
Enterokinase breaks a peptide bond between the N-terminal 6
amino acids to form mature trypsin.
Formation of an active form of trypsin in the pancreatic cells
would result in proteolytic digestion of the cell.
Specific trypsin inhibitors produced by the body that bind to the
active site and block enzyme activity.
How is the General Fertility Rate calculated?
State ONE ADVANTAGE that General Fertility Rate has with
respect to the Crude Birth Rate?
State ONE DISADVANTAGE that General Fertility Rate has
with respect to the Crude Birth Rate.
General Fertility Rate = (Number of live births [in a year]) /
(Number of 15-44 year old women).
The General Fertility Rate denominator is relevant to giving
birth, i.e. fertile women.
The General Fertility Rate requires the number of 15-44 year old
women to be known which is difficult to ascertain in some
parts of the world.
What substrates can be converted to glucose in the liver
Galactose. Glycerol. Fructose. Pyruvate. Lactate. Glucogenic amino acids.
