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pom last minute stuff > molecular biology > Flashcards

molecular biology Flashcards

1
Q

redox reaction

A

electron transfer

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2
Q

ligation requiring atp cleavage

A

covalent bond formation

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3
Q

enzyme order in glycolysis

A

hexokinase
phosphoglucose isomerase
phosphofructokinase
aldolase
TPI

glyceraldehyde 3 phosphate dehydrogenase
phophoglycerate kinase
phosphoglycerate mutase
enolase
pyruvate kinase

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4
Q

fermentation

A

pyruvate => acetoacetate => ethanol

H+ > Co2 , NADH + H+ > NAD

pyruvate decarboxylase + alcohol dehydrogenase

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5
Q

lactase generation

A

pyruvate => lactate

NADH + H+ > NAD

lactate dehydrogenase

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6
Q

A-CoA formation

A

pyruvate + HS-CoA => ACoA + CO2

NAD+ > NADH

PDH comple

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7
Q

thioester bond

A

in acetyl co A
high energy linkage - readily hydrolysed
gives molecules acetate

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8
Q

beri-beri disease

A

thiamine deficiency (vitB)

NS damage, weakness, dec cardiac output

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9
Q

creatine phosphate

A

buffer for ATP

CP <=> C + ATP

creatine kinase + ADP used

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10
Q

TCA

A

(acetyl CoA)

citrate
isocitrate
akg
succinyl CoA
succinate
fumerate
malate
oxaloacetate

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11
Q

TCA products

A

NADH x3
FADH2 x1
GTP x1

CO2 x2

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12
Q

aa degradation

A

amino group removed - cytoskeleton => glucose production or TCA

pyruvate, ACoA, acetoacetyl CoA, akg, succinyl CoA, fumerate, oxaloacetate

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13
Q

transamination

A

amine group from aa transferred to keto acid => new pair

alanine + akg => pyruvate + oxaloacetate

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14
Q

components of glycerol phosphate shuttle + where

A

DHAP, Glycerol 3P

cytosolic + mito G3P dehydrogenase

NADH + H+ => NAD+
FAD+ => FADH2
Q2 => QH2

in skm + brain

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15
Q

components of malate aspartate shuttle

A

aspartate - oxaloacetate - malate

akg <=> glutamate, NADH <=> NAD+

aspartate-glutamate antiporter
malate-akg antiporter

aspartate transaminase
malate dehydrogenase

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16
Q

TCA cancer defects

A

mutations in: isocitrate dehydrogenase, fumerase, succinate dehydrogenase

decreased TCA but increased aerobic Glyc (Warburg effect)

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17
Q

warburg effect

A

preferential generation of lactate even when O2 present

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18
Q

carnitine shuttle components

A

carnitine => acyl carnitine => translocase => carnitine

acyl-CoA => CoA

carnitine acyl transferase 1&2

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19
Q

primary carnitine deficiency

A

mutation in SLC22A5 = carnitine transporter disfunction = cells cant take up carnitine

encephelopathy, cardiomyopathy, muscle weakness + hypoglycaemia

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20
Q

beta oxidation steps

A

Acyl-CoA made from FA

carnitine shuttle => transports acyl coA into matrix

oxidation
hydration
oxidation
thiolysis

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21
Q

16C palmitoyl b-ox

A

P + 7FAD + 7NAD+ + 7H20 + 7CoA =>

8A-CoA + 7FADH2 + 7NADH

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22
Q

ketone bodies

A

made when not enough carbs = increased fat breakdown = energy for brain

(TCA in brain => A-CoA made from KB)

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23
Q

why KB not made in liver in starvation

A

gluconeogenesis = uses oxaloacetate
no oxaloacetate for TCA
no point of making A-CoA via KB as TCA cant go on anyway

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24
Q

KBs

A

acetoacetate
acetone
D3 hydroxy-butyrate

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25
Q

fatty acid biosynthesis

A

sequential decarboxylative condensation which elongates acyl CoA by 2C

ELONGATION => REDUCTION => DEHYDRATION => REDUCTION

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26
Q

b-ox vs FA synthesis

A

carrier = CoA vs ACP

reducing power = FAD/NAD+ vs NADPH

location = mito vs cyto

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27
Q

FA desaturation

A

fatty acyl-coA desaturases

add double bonds

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28
Q

MCADD

A

medium chain (6-12) acyl CoA dehydrogenase deficiency

(first enz of B-ox)

auto rec, heel prick test, no fasting over 10-12 hours (IV glucose if necessary)

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29
Q

epithelial functions

A

transport, absorption, secretion, protection

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30
Q

simple squamous epithelium + 3 examples

A

thin => exchange

e.g
lung alveolar (air sac) epithelium
mesothelium (lining major body cavities)
endothelium lining blood vessels and other blood spaces

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31
Q

simple columnar epithelium + 1 example

A

absorption/secretion

e.g enterocytes lining the gut

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32
Q

keritinizing stratified squamous epithelium + 1 example

A

produce keratin + die = thicker, stronger + protective
lose cellular organelles and nuclei
not visible under light microscopy

e.g epidermis

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33
Q

non-keritinizing stratified squamous epithelium + 5 examples

A

do not undergo keratinisation
retain nuclei + organelles

e.g. epithelium lining the mouth, oesophagus, anus, cervix and vagina

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34
Q

pseudo-stratified epithelium + 2 examples

A

appears to be multi-layered but surface cells all have contact with basal lamina

e.g.
airway (trachea and bronchi) epithelium
various ducts in the urinary and reproductive tracts

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35
Q

how solutes cross membranes

A

gases + hydrophobic molecules = diffuse across the lipid bilayer

most molecules = passive/active using proteins

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36
Q

cell polarisation

A

when cell organelles + membrane proteins are organised to give the cell directionality

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37
Q

absorptive epithelium

A

apical:
brush border + cells arranged as villi = more SA
BB = active transporters and channels = more uptake
many mitochondria

baso:
passive transport
(absorb things into bloodstream e.g intestinal brush border absorbs nutrients)

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38
Q

exocrine vs endocrine secretory epithelium

A

exocrine = secretion into duct or lumen => organelles arranged for secretion from apical membrane

endocrine = into blood so organelles arranges towards basolateral membrane

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39
Q

too little proliferation e.g

A

inhibition of stem cell proliferation in intestinal crypts due to chemotherapy leading to gastro-intestinal disturbances

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40
Q

too much proliferation

A

overproduction of tissue as rate of cell loss isn’t sufficient to maintain normal tissue volume

e.g tumours

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41
Q

proliferation at epidermis

A

cells of basal layer of stratified squamous epithelia divide + migrate up to replace cells lost from surface

undergo differentiation => flattening + keratinising

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42
Q

cell turnover summary

A

cell loss = cell production ==> steady state

cell loss > cell production ==> reduction in tissue mass

cell loss < cell production ==> increased tissue mass

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43
Q

where is CK found

A

in all cells at low levels
high levels in metabolically active tissues

only in cells - if in blood => cell death has occurred

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44
Q

CK types

A

skm = MM
brain = BB
cardiac muscle = MB

all = same weight (43Dka) but different charges

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45
Q

why most atp in mito

A

where most A-CoA made

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46
Q

methods of obtaining fat

A

denovosynthesis by liver
diet
adipose

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47
Q

bile salts

A

emulsify fats + fat soluble vits ADEK

made in liver => stores in GB

have hydrophobic + hydrophillic sides

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48
Q

orlistat

A

inhibits pancreatic + gastric lipases = decreased fat absorption
lipstatin derivative

abd pain, urgency to defacate, increased flatus + steatorrhoea

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49
Q

lipoprotein

A

lipid transport in plasma

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50
Q

chylomicron formation

A

after enterocytes absorb digestion products in small intestine brush border, triglycerides are resynthesised in golgi and form CMs

need apoproteins from HDL in bloodstream

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51
Q

chylomicron function

A

dietary fat transport

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52
Q

lipoprotein lipase

A

breaks down triglycerides carried by CMs, allowing fatty acids + glycerol to enter tissues

FA = b-ox, Gly = gluconeogenesis in liver

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53
Q

main stages of cholesterol formation

A

synthesis of isopententyl pyrophosphate

condensation of IPP to form squalene

cyclisation and demethylation of squalene to form cholesterol

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54
Q

cholesterol function

A

steroid precursor

increases and decreases membrane fluidity

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55
Q

how are bile salts synthesised
(+ name 2 primary bile salts)

A

cholesterol is broken down by series of reactions

glycholate + taurocholate

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56
Q

structure, function + types of lipoproteins

A

phospholipid monolayer with apoproteins surrounding cholesterol esters and triglycerides

transports hydrophobic lipids in aqueous environment

VLDL, LDL, IDL, HDL

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57
Q

formation of cholesterol esters
(where, substrates, enzyme, by-product)

A

made in plasma

substrates: cholesterol + acyl chain of phosphatidyl-choline

enzyme: lecithin-cholesterol acyl transferase

by product: lysophosphatidyl choline

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58
Q

HDL

A

‘good’

cholesterol from tissue to liver for use/disposal (reverse cholesterol transport)

reduces blood cholesterol levels

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59
Q

LDL

A

‘bad’

cholesterol from liver to tissue

increases tissue cholesterol

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60
Q

familial hypercholesterolaemia

A

monogenic dominant => serum cholesterol increased

single mutation = 2-3x = atherosclerosis in middle age

double = 5x = severe atherosclerosis + coronary infarcts in adolesence

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61
Q

xanthomas

A

bumps on skin due to deposition of plasma LDL derived cholesterol to macrophages of skin (familial hypercholesterolaemia)

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62
Q

statin function

A

inhibit HMG-CoA reductase in step 3 of cholesterol formation

e.g lovastatin

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63
Q

resins

A

binds/sequesters bile acid-cholesterol complexes - prevent reabsorption in intestine

lowers LDL + increases HDL

e.g cholestryamine

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64
Q

metabolic features of brain

A

need continuous supply of glucose
cannot metabolise fatty acids
can sometimes use ketone bodies e.g β-hydroxybutyrate (not ideal)

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65
Q

hypoglycaemia vs hyperglycaemia on brain

A

hypo = faintness and coma
hyper = irreversible organ damage

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66
Q

metabolic features of skeletal muscle

A

ATP requirement varies depending on exercise

light = OxPhos
vigorous = O2 limiting factor = glycogenolysis = lactate formation

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67
Q

metabolic features of heart

A

completely aerobic metabolism - rich in mitochondria
uses tca substrates e.g. free fatty acids, ketone bodies

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68
Q

what happens to acetyl coA during fasting

A

rather than enter the TCA => produce ketone bodies

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69
Q

nucelotide production from glucose metabolism

A

pyruvate + other TCA cycle intermediates = source of amino acids => backbone used to make nucleotides

e.g
glucose-6-phosphate via pentose phosphate pathway = nucleotide source => generates bulk of NADPH needed for anabolic pathways

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70
Q

how does body avoid hypoglycaemia in the short term [3]

A

breakdown of liver glycogen = maintains plasma glucose

free fatty acid release from adipose tissue

convert Acetyl CoA into ketone bodies via liver

(fatty acids + KBs used by muscle = more plasma glucose available for brain)

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71
Q

lactate in gluconeogenesis

A

made by skeletal muscle during strenuous exercise - when rate of glycolysis exceeds rate of TCA + ETC

taken up by liver + used to regenerate pyruvate by lactate dehydrogenase (LDH) = Cori cycle

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72
Q

amino acids in gluconeogenesis

A

derived from diet or break down of skm during times of starvation

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73
Q

triglycerides in gluconeogenesis

A

hydrolysed = fatty acids and glycerol
glycerol backbone = used to generate dihydroxyacetone phosphate

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74
Q

irreversible reactions in glycolysis enzymes

A

hexokinase, phosphofructokinase and pyruvate kinase

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75
Q

why are bypass reactions required

A

ΔG for straight reversal of glycolysis = +90 kJ/mol = energetically unfavourable

ΔG for gluconeogenesis = -38 kJ/mol

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76
Q

bypass enzymes

A

pyruvate carboxylase
phosphoenolpyruvate carboxykinase
fructose 1,6 biphosphatase
glucose 6 phosphatase

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77
Q

glucogenic vs ketogenic amino acids

A

g: skeletons give rise to glucose via gluconeogenesis

k: skeletons cant enter gluconeogenesis - used to synthesise fatty acids + ketone bodies

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78
Q

why cant fatty acids be converted into glucose by gluconeogenesis

A

fatty acids converted by beta oxidation into acetyl coa

TCA cycle: acetyl CoA + oxaloacetate = citrate etc
two carbon atoms = sequentially lost as CO2
oxaloacetate regenerated
no net synthesis of oxaloacetate or pyruvate to enter gluconeogenesis

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79
Q

light contraction - aerobic respiration [4]

A

OxPhos

glucose from blood to muscle => glycolysis + TCA => ATP from cofactor re-oxidation

demand for atp increase due to increased req for muscle actomyosin ATPase + cation balance

more glucose needed => more glucose transporters on muscle cell membrane

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80
Q

adrenalin in aerobic respiration

A

increases:

rate of glycolysis in muscle
rate of gluconeogensis by liver
increases release of fatty acids from adipocytes

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81
Q

anaerobic resp

A

atp demand not met by O2 delivery
transport cant keep up with demand for glucose

muscle glycogen breakdown
lactate increased

in recovery: liver uses lactate to form glucose

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82
Q

2 methods of controlling metabolic pathways

A

product inhibition

signalling molecules such as hormones

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83
Q

Michaelis constant (KM)

A

used to compare relative activities of enzymes

concentration of substrate at which an enzyme functions at a half-maximal rate (Vmax)

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84
Q

muscle hexokinase (1)

A

low Km so active at low concentrations of glucose => operating at maximal velocity at all times

sensitive to inhibition G6P
anaerobic conditions = rate of TCA cycle drops + glycolysis slows as Hk I = inhibited by accumulating levels of G6P

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85
Q

liver hexokinase (4)

A

high Km so less sensitive to blood glucose concentrations (need higher concentration to work)

also less sensitive to inhibitory effects of G-6-P

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86
Q

glucose 6-phosphatase

A

liver, but not all muscle

catalyses reverse reaction of hexokinase
generates glucose from glucose-6-phosphate

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87
Q

complications of diabetes [4]

A

hyperglycaemia with progressive tissue damage (e.g. retina, kidney, peripheral nerves)

increased plasma FAs + lipoprotein = cardiovascular complications

increased KB => ketoacidosis

hypoglycaemia = coma if insulin dosage imperfectly controlled

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88
Q

substrate-level phosphorylation

A

production of ATP by direct transfer of a high-energy phosphate group from intermediate substrate to ADP

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89
Q

oxidative phosphorylation

A

ATP produced using energy derived from the transfer of electrons in an electron transport system

inner mito memb

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90
Q

membrane proteins + mobile carriers in electron transport chain

A

complex I (a.k.a NADH dehydrogenase)
complex II (a.k.a. Succinate dehydrogenase)

carrier => co-enzyme Q (a.k.a. ubiquinone)

complex III (a.k.a. Q-cytochrome C oxidoreductase)

carrier => cytochrome C (not shown)

complex IV (a.k.a. cytochrome c oxidase)

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91
Q

what happens along electron transport chain

A

complexes 1/2, 3 + 4 accept electrons + energy released moves H+ from matrix to intermembrane space

forms concentration gradient for H+

electrons in 4 used to convert O2 => H2O

H+ down conc grad through ATP back into matrix => ATP made

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92
Q

why does IV pump 2 H+ across

A

cytochrome c moves 2e- one at a time from III to IV so it pumps 2H+ (once every time it receives an electron)

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93
Q

why does fadh2 make less atp than nadh

A

membrane protein II = part of TCA - doesn’t pump H+ across

as I is bypassed - fewer protons pumped across so less ATP made

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94
Q

redox couple

A

substrate that can exist in reduced or oxidised form

e.g:
NAD+/ NADH
FAD / FADH2
Fe3+/Fe2+
½ O2/H2O

95
Q

redox potential

A

ability of redox couple to accept or donate electrons

96
Q

standard redox potential

A

measured using hydrogen electrode as reference = E0

97
Q

negative vs positive E0

A

-ive: redox couple has a tendency to DONATE electrons and therefore has more REDUCING power than hydrogen

+ive: redox couple has a tendency to ACCEPT electrons and therefore has more OXIDISING power than hydrogen

98
Q

how is the ETC energetically favourable

A

along chain - channels + carriers = more +ive E0 = have more affinity for electrons

as electrons progress along the chain, they lose energy

99
Q

ATP synthase structure

A

2 subunits:
F0 = membrane bound = a,b,c subunits
F1 = projects into matric = a,b,g subunits

H+ passes through F0 - F1 rotates, generating energy for ADP => ATP
rotating opposite way = ATP hydrolysis

100
Q

oxygen electrode

A

platinum cathode: O2 + 4H+ + 4e- => 2 H2O
silver anode: 4 Ag0 + 4Cl- → AgCl + 4e

current produced = proportional to O2 conc in chamber => used to see what substances affect Ox-Phox

101
Q

cyanide (CN) + azide (N3-)

A

bind with high affinity to ferric (Fe3+) haem group in complex IV
blocks flow of electrons through chain = no ATP made

HALTS ETC + ATP PRODUCTION

102
Q

malonate

A

resembles succinate - competitive inhibitor (II)

SLOWS FLOW OF ETC - only inhibits use of FADH2 - NADH can still be used

103
Q

dinitrophenol

A

weightloss

increases metabolic activity as it bypasses ATP synthase + moves H+ back into matrix

results in higher metabolic activity = more O2 consumption

104
Q

non-shivering thermogenesis

A

UCP-1 activated in response to drop in core body temperature
H+ flow back into matrix

ATP synthase = bypassed + energy from H+ gradient = dissipated as heat

105
Q

rotenone

A

inhibits e- movement from 1 => Q

SLOWS ETC FLOW (fadh can still be used)

106
Q

oligomycin

A

AB made by streptomyces
binds ATP synthase stalk so H+ cant move through

STOPS ATP SYNTHESIS

107
Q

cell cycle

A

orderly sequence in which cell duplicates + divides in two

involves: duplication, division and co-ordination

108
Q

G0

A

quiescent phase
where cells go in absence of stimulus
dormant phase

109
Q

non-dormant but non-div cells

A

neurons, skm, hepatocytes

110
Q

what 2 things can happen at each checkpoint

A

cell is fine/repaired = move onto next stage
apoptosis

111
Q

why do cells leave G0 [4]

A

growth factors (stimulus) => growth factor receptors

trigger intracellular signalling pathways

protein synthesis increased + degradation decreased

promotes movement into G1 - leads to signal amplification + integration/modulation into other pathways

112
Q

c-Myc [4]

A

transcription factor induced by growth factor

stimulates expression of cell cycle genes

promotes G0 => G1

oncogene - over expressed in many tumours

113
Q

cdk

A

cyclin dependant kinase

in all proliferating cells but only active when cyclin bound (levels of cyclin fluctuate within cell)

cyclin:cdk complex only active during mitosis

114
Q

function of cdk

A

phosphorylate + dephosphorylate proteins to control key signalling events

(only at hydroxyl groups = serine/threonine/tyrosine)

115
Q

complex is required for entry into cell cycle

A

cdk 4/6 : cyclin D complex

116
Q

cdk examples and properties

A

Cdk 1,2,4,6
present in all proliferating cells throughout life
activity regulated by cyclin interaction + phosphorylation

117
Q

what enzyme dephosphorylates at inhibitory site

A

activating protein phosphatase

118
Q

how are cyclins turned off

A

by ubiquitination (ubiquinone added) => destruction

119
Q

retinoblastoma

A

tumor suppressor in all nucleated cells

molecular brake - sequesters transcription factor in inactive form = cant turn on genes for cell cycle (dna polymerase + thymidine kinase)

120
Q

Rb in proliferating cell

A

GF => intracellular signalling pathway

G1-cdk + G1/S-cdk complex production

complexes phosphorylate Rb = inactivation => release TF

121
Q

p53 action

A

(tumour suppressor - arrests cells with damaged dna in G1)

dna damage => activation of protein kinases that activate p53

activate + stabilise it

active p53 binds regulatory region of p21 gene

p21 gene transcribed = p21 mRNA

p21 = cdk inhibitor protein = inactivate cyclin-cdk complexes

no dna damage => degraded in proteasomes

122
Q

signalling between membrane attached proteins

A

plasma membrane proteins on adjacent cells interacting

123
Q

ionotropic receptors

A

ligand binds receptor on channel protein

conformation change of channel protein => opens pore

pore allows ions in + out of cell according to conc grads

124
Q

G-protein coupled receptors

A

7-TM receptor + heterotrimeric G-protein = inactive

ligand binding => conformation change of receptor

unassociated G-protein binds receptor => GDP is exchanged for GTP

G-protein dissociates into two active components: a-subunit + bg subunit

subunits bind their target proteins

internal GTPase activity on a-subunit dephosphorylates GTP to GDP => a dissociates from target protein = inactive

(receptor = active as long as ligand bound + can activate further heterotrimeric G-proteins)

125
Q

enzyme linked receptor

A

ligand binding => receptors clustering

activates enzyme activity within cytoplasmic domain

enzymes phosphorylate receptor

phosphorylation => binding of signalling proteins to cytoplasmic domain

signalling proteins => recruit other signalling proteins = signal is generated within cell

126
Q

intracellular receptors (cytoplasmic)

A

in cytosolic compartment
associated with chaperone molecules (heat shock proteins, hsp)

hormone binds receptor => hsp dissociates

2 hormone bound receptors form a homodimer

homodimer translocates to nucleus => binds to DNA

127
Q

intracellular receptors (nuclear)

A

within nucleus

binding of hormone ligand => transcriptional regulation

128
Q

why do cells need to communicate

A

process information (e.g sensory)
self preservation
voluntary movement
homeostasis

129
Q

collagen types

A

type I, II, III (fibrillar)
type IV (basement membrane)

130
Q

multi-adhesive glycoproteins

A

fibronectin, fibrinogen
laminins (basement membrane)

131
Q

proteoglycans

A

aggrecan, versican, decorin
perlecan (basement membrane)

132
Q

what matrix protein gene mutation causes osteogenesis imperfecta

A

type 1 collagen

133
Q

what matrix protein gene mutation causes marfan’s syndrome

A

fibrillin 1

134
Q

what matrix protein gene mutation causes alport’s syndrome

A

type IV collagen (alpha 5 chain)

135
Q

what matrix protein gene mutation causes epidermolysis bullosa

A

laminin 5 (all 3 chains)

136
Q

what matrix protein gene mutation causes congenital muscular dystrophy

A

laminin 2 (alpha 2 chain)

137
Q

what gene mutation affects ECM catabolism and therefore causes hurler’s syndrome

A

L-alpha-iduronidase

138
Q

which fibrotic disorders are caused due to excessive ECM deposition

A

liver fibrosis = cirrhosis
kidney fibrosis = diabetic nephropathy
lung fibrosis = idiopathic pulmonary fibrosis

139
Q

arrangement of collagen fibrils

A

succesive layers at right angles to each other
allows resistance to tensile force in all directions

140
Q

collagen triple helix

A

3 alpha chains = stiff structure
each chain = gly-x-y repeat

glycine = every third position = small enough to occupy interior (smallest aa - H-side chain)

x = proline, y = hydroxyproline (often)

141
Q

how does procollagen become collagen (fibrillar)

A

newily synthesised procollagen has non collagenous domains at N and C-termini

removed after secretion in fibrillar collagens (remain for other types)

142
Q

crosslinking in collagen

A

provides tensile strength and stability
involves lysine and hydroxy-lysine

type + amount changes with age

143
Q

how does vitamin C deficiency cause scurvy

A

vit-c def = under-hydroxylated collagens = poor tissue stability = scurvy

144
Q

ehlers-danlos syndrome

A

affect: collagen production, collagen structure, collagen processing

stretchy skin + loose joints

145
Q

what do fibril associated collagens do (e.g 9/12)

A

don’t form fibrils themselves, instead associate with fibrillar collagens + regulate the organisation of collagen fibrils

146
Q

type IV collagen
(what, structure, where)

A

network-forming collagen

N+C terminal propeptides not cleaved => interact to form sheet => dimer > tetramer

in all basement membranes - changes depending on tissue type

147
Q

what is the basement membrane made of

A

laminin + collagen 4

148
Q

laminins
(structure, 3 functions)

A

large heterortrimeric multi-adhesive proteins = α chain + β chain + γ chain (cross)

interact with many cell surface receptors (e.g. integrins + dystroglycan)

can self-associate as part of basement membrane matrix

can also interact with other matrix components (e.g. type IV collagen, nidogen and proteoglycans)

149
Q

laminin arms

A

short => maintain basement membrane stability => self associate => interact with integrins and nidogen

long => cell to cell interactions/cell adhesion => bind cell surface receptors like integrins, dystroglycans or perlecan

150
Q

laminin-alpha 2 deficiency and muscular dystrophy

A

LAMA 2 gene => laminin a2
a2 + B1 + y1 = heterotrimer (laminin 211)

congenital MD = no LAMA 2 = no a2
laminin fails to interact with α7β1 integrin + α-dystroglycan (adhesion + BM assembly)

lack of a2 = progressive muscle weakness and degeneration

151
Q

diabetic nephropathy

A

accumulation of extracellular matrix = highly thickened basement membrane

restricts renal filtration and can lead to renal failure

152
Q

alport syndrome

A

abnormally split and laminated glomerular BM = progressive loss of kidney function

153
Q

elastin
(arrangement, structures within, elastic fibre structure)

A

small protein arranged in random coil
alternating hydrophobic + hydrophilic domains

hydrophilic domains = lysine residues => cross-linked during mature elastin formation

elastic fibres = elastin core - surrounded by microfibrils rich in fibrillin

154
Q

marfan’s syndrome

A

fibrillin-1 mutation = disorganisation of elastic fibres

thickening of aorta due to fragmentation + disarray of elastic fibres => predisposition to aortic ruptures

arachnodactyly = spider-like fingers

155
Q

fibronectin
(what is it, interactions, functions)

A

disulphide linked dimer

interact with cell surface receptors + other matrix molecules

regulate cell adhesion + migration in embryogenesis + tissue repair

help promote blood clotting

156
Q

integrins + fibronectins

A

integrins = transcellular

bind cytoskeleton components e.g actin to fibronectin

fibronectin then binds ligands such as collagen

157
Q

proteoglycans

A

core proteins with attached glycosaminoglycan chains

chains = repeating disaccharides (sulfation + carboxylation can increase negative changes)

158
Q

glycosaminoglycan varieties

A

hyalaurin

deermatan sulfate (decorin)

heparan sulfate (syndecan)

keratan sulfate + chondroitin sulfate (aggrecan)

159
Q

hyaluronan

A

GAG without core protein

in highly viscous tissues e.g. vitreous humour of eye + synovial fluid of joint

protects cartilaginous surface from damage

160
Q

aggrecan (+how is it able to resist compressive forces)

A

in cartilage matrix : negative charge due to highly sulfated GAGs + -ive carboxyl groups
attract cations such as Na+ which are osmotically active
leads to water retention in -ive environment

under compressive load - water = lost, regained once load is reduced
so aggrecan = resist compressive forces.

161
Q

ECM degradation in osteoarthritis

A

aggrecan cleavage by aggrecanases and metalloproteinases

cushioning properties of cartilage over the end of bones = lost

162
Q

cell death order

A

cellular function lost before cell dies
only then are morphological changes seen

163
Q

atrophy

A

shrinkage in size of cell (or organ) by loss of cell substance

164
Q

hypertrophy
(what is it, causes, examples)

A

increase in size of cells + consequently increase in size of organ

physiological or pathological
caused either by increased functional demand or specific hormonal stimulation

phys: hypertrophy of uterus during pregnancy
path: hypertension, valve disorders, other structural analysis and hormones

165
Q

hyperplasia
(what is it, causes, examples)

A

increase in the number of cells in an organ

physiological: either hormonal or compensatory - proliferation of endometrium during menstrual cycle or when one kidney removed, other becomes larger as compensation

pathological: usually due to excessive hormonal or growth factor stimulation - cancers

166
Q

metaplasia
(what is it, causes, examples)

A

reversible change in which one adult cell type is replaced by another

phys: cervix expands in pregnancy => columnar epithelium = exposed to acid pH of vagina => squamous epithelium
when cervix shrinks back = back to columnar

path: barretts oesophagus

167
Q

dysplasia
(what is it, causes, examples)

A

precancerous cells that show genetic + cytological features of malignancy but not invading underlying tissue

intermediate phase between non-cancerous and cancerous

KEY: have increased nuclear:cytoplasmic ratio

168
Q

light microscopic changes associated with reversible injury

A

fatty change
cellular swelling

169
Q

degenerative changes

A

changes associated with cell and tissue damage

170
Q

necrosis

A

confluent cell death (whole areas of cells) giving rise to secondary inflammation

coagulative necrosis
liquefactive necrosis
caseous necrosis
fat necrosis

171
Q

coagulative necrosis

A

structure is still recognisable even though tissue is dead

occurs when blood flow to cells stops or slows (ischemia)

occurs anywhere but the brain

172
Q

coagulative necrosis

A

structure is still recognisable even though tissue is dead

occurs when blood flow to cells stops or slows (ischemia)

occurs anywhere but the brain

173
Q

liquefactive necrosis

A

cells turn to liquid when they die

only in brain due to lack of structural support

174
Q

caseous necrosis

A

cheese like appearance (particularly brie?)

most commonly in lobes of lung due to pulmonary tuberculosis

(cant see normal structure like coagulative - cant see liquid like liquefactive - just granular appearance at necrosis site)

175
Q

fat necrosis

A

mainly in pancreas but can occur when any other fat tissue is damaged

e.g acute pancreatitis = leaking enzymes (e.g lipases) in pancreas - hydrolyses fat => free fatty acids

free fatty acids combine with calcium = deposits as fat necrosis

176
Q

cell membrane in apoptosis vs necrosis

A

cell membrane remains intact in apoptosis - may split into parts + consumed by phagocytes

in necrosis - cell membrane degraded = leakage of cellular contents = inflammation

177
Q

physiological causes of apoptosis

A

embryogenesis

deletion of auto-reactive t cells in the thymus

hormone-dependent physiological involution

cell deletion in proliferating populations

a variety of mild injurious stimuli that cause irreparable dna damage that, in turn, triggers cell suicide pathways

178
Q

apoptosis

A

programmed cell death in which a series of molecular steps in a cell lead to its death

179
Q

differences between apoptosis and necrosis

A

apoptosis may be physiological

apoptosis is an active energy dependent process

apoptosis not associated with inflammation

180
Q

necroptosis

A

programmed cell death associated with inflammation

caused by things like viral infections

181
Q

causes of cell injury [8]

A

oxygen deprivation
chemical agents
infectious agents
immunological reactions
genetic defects
nutritional imbalances
physical agents
aging

182
Q

what does cellular response to injurious stimuli depend on

A

type of injury
duration of stimulus
severity

183
Q

vulnerable intracellular systems [4]

A

cell membrane integrity
ATP generation
protein synthesis
integrity of genetic apparatus

184
Q

lethal vs sublethal

A

sublethal = produces injury not amounting to cell death - may be reversible or progress to cell death

lethal = produces cell death

185
Q

plasma vs interstitial fluid

A

plasma is like interstitial fluid (IF) except plasma has more protein

186
Q

osmolarity

A

measure of the concentration of all solute particles in a solution

187
Q

osmoles

A

number of moles of solute that contribute to the osmotic pressure of a solution

188
Q

tonicity

A

capability of solution to modify volume of cells by altering water content

determined by impermeant solutes - those that cannot cross the cell membrane

189
Q

hypertonic solutions

A

less conc outside than inside of impermeant solutes so cell swells + bursts

190
Q

why dont cells burst

A

Na+K+ ATPase
makes cell essentially impermeable to Na+ as it pumps it all out as it enters
water can’t enter cell = cant burst

191
Q

university of wisconson solution

A

flush + cool kid/liv/panc organs when taken from from donor in prep for storage, transportation + transplantation

cooling => ischaemic changes caused by loss of blood supply = slowed

192
Q

main factors that reduce cell swelling in UW-infused tissues

A

lack of Na+ or Cl- (so no influx possible)

presence of extracellular impermeant solutes (lactobionate ions, raffinose)

presence of a macromolecular colloid (starch)

193
Q

allopurinol + glutathione

A

antioxidants

helps protect organs from damage from reactive oxygen species (ROS)

194
Q

main methods of crossing endothelial layer

A

lipid soluble = through cells

small water soluble = through pores between cells

exchangeable proteins = vesicular transport

plasma proteins generally cannot pass out of BVs

195
Q

colloid osmotic pressure

A

osmotic pressure exerted by large molecules - holds water within vascular space

generated by higher concentrations of plasma proteins inside the capillary than outside

pressure draws fluid into capillary

196
Q

hydrostatic pressure

A

pressure that any fluid in a confined space exerts

e.g generated by flow of blood through a vessel

high hydrostatic pressure pushes fluid out of capillary

197
Q

oedema

A

accumulation of fluids within tissues

due to imbalance in fluid exchange in tissues causing fluid to accumulate in the interstitial spaces

commonly caused by increase in permeability of capillary walls

leaky capillary => proteins lost => reduced COP = fluids more readily pushed out from capillary

198
Q

function of lymphatic capillaries

A

combat loss of plasma fluids into tissues by collecting interstitial fluid + return to blood circulation

199
Q

inflammatory oedema

A

inflammation caused by local blood vessels becoming leaky due to things like insect bites

swelling as rate of leakage from vessels is greater than rate of drainage by lymphatics

200
Q

hydrostatic oedema

A

high BP = increased hydrostatic pressure in vessels

pushes more fluid out of vessels => accumulation of interstitial fluid

201
Q

oedema in breast cancer survivors

A

breast cancer treatment = axillary (armpit) lymph nodes removed

can remove pathway of drainage from upper limb on the affected side = accumulation of fluid

202
Q

elephantiasis

A

parasitic worms block lymphatic vessels

prevent drainage of lymph

preventing drainage of interstitial fluid from specific areas

203
Q

4 main signs of inflammation (+ 1 extra)

A

redness
swelling
heat
pain

loss of function

204
Q

inflammation definition + why does it occur

A

rapid non-specific response to cellular injury

removes cause and consequence of injury

(complex + tightly regulated)

205
Q

general flow of events leading to redness at inflammation site

A

change in local blood flow

structural changes in microvasulature

recruitment of immune cells + proteins

206
Q

stages of acute inflammation

A

steady skin
damage
immune cell recruitment
neutrophil extravasation
neutrophil function at inflammation site
resolution

207
Q

what happens when there is damage to tissue (stage 2 of acute)

A

non-apoptotic cell death or detection of foreign material = inflammatory signals

degranulation of mast cells => vasodilator release (histamine + NO)

vascular changes => dilation, increased permeability, reduced flow + plasma leakage)

208
Q

benefits of increased vascular permeability and leakage at inflammation site

A

more: antibodies, proteins, leukocyte migration

barrier formation between inflammation and healthy tissue

209
Q

exudate

A

fluid, proteins and cells that have seeped out of a blood vessel

210
Q

how are inflammatory cell recruited (stage 3 of acute inflammation)

A

recruitment and inflammation signals e.g. chemokines produced at site of damage

diffuse out to form a gradient

leukocytes expressing complementary chemokine receptors migrate toward the chemokine source

211
Q

at does the chemokine CXCL8 do (otherwise known as IL8)

A

binds CXCR 1 + CXCR 2 (g-coupled 7TM protein receptors)

stimulate recruitment of neutrophils

212
Q

neutrophil extravasation steps

(neutrophil exits capillary => enters tissue)

A

CHEMO-ATTRACTION => cytokines stimulate endothelial up-regulation of adhesion molecules (e.g selectins)

ROLLING ADHESION => carbohydrates in low affinity state on neutrophils bind selectins (integrins e.g PSGL 1)

TIGHT ADHESION => chemokines promote switch from low to high affinity integrins = enhance ligand binding e.g ICAM1/2

TRANSMIGRATION => cytoskeletal rearrangement + extension of pseudopodpia = squeeze through endothelium
=> mediated by PECAM interactions

213
Q

neutrophil functions at site of inflammation

A

pathogen recognition
pathogen clearance => phagocytosis/netosis
cytokine secretion => recruit + activate other immune cells

214
Q

recognition of gram negative bacteria by neutrophils

A

TLR4 and CD14 used to identify lipopolysaccharides (LPS) present in gram-negative bacteria

215
Q

phagocytosis process

A

large particles engulfed into membrane bound vesicles (phagosomes)

phagosome fuses with lysosome (vesicles containing enzymes e.g. elastase and lysozyme) => phagolysosome

reactive oxygen species (ROS) – phagocyte NADPH oxidase + antimicrobial peptides – e.g. defensins released

216
Q

key factors of chronic inflammation (i.e. how it differs to acute)

A

persistent inflammatory stimuli => (persistent infection/allergen/toxic stimuli, unclearable particulates, autoimmunity - self ag)

distinct immune cell infiltrate => (inflamm macrophages, T-lymphocytes, plasma cells)

vicious cycle => no clearance, bystander tissue destruction, concurrent repair process

217
Q

why are phagocytes kinda bad in chronic inflammation

A

normally => help in wound repair - deposition of collagen etc

when chronic inflammation => trying to both clear and build at same time => fibrotic scarring

218
Q

good vs bad effects of macrophages

A

good: phagocytic, cytotoxic, anti-inflammatory, wound repair

bad: cytotoxic, inflammatory, pro-fibrotic

219
Q

granulomatous inflammation

(what is it, why, trigger)

A

chronic inflammation with distinct pattern of granuloma formation

aggregation of activated macrophages => form barrier designed to stop pathogen escaping + allow clearance

triggered by strong T cell response +

220
Q

how does TB use granulomas to hide

A

infects macrophages => formation of granuloma => becomes latent => reactivated once immunocompromised => aggressive replicating

221
Q

positives of inflammation

A

clear inflammatory agent

remove damaged cells

restore normal tissue function

222
Q

negatives of inflammation

A

excess tissue damage

scarring

loss of organ function -> organ failure

223
Q

Tumour

A

Any kind of mass forming lesion
neoplastic or non-neoplastic

224
Q

neoplasm

A

autonomous (free) growth of tissue which have escaped normal constraints on cell proliferation

can be benign (localised) or malignant (invade locally or spread to other tissues)

225
Q

hamartomas

A

localised benign overgrowths of one of more mature cell types

represent architectural but not cytological abnormalities

for example: lung hamartomas = composed of cartilage + bronchial tissue

226
Q

heterotopias

A

normal tissue being found in parts of the body where they are not normally present

for example: pancreas in the wall of the large intestine

227
Q

classification of neoplasms

A

primary description = based on cell origin
secondary description = benign or malignant (diff suffixes)

228
Q

benign + malignant epithelial tumours
(oma = benign, sarcoma = malignant)

A

squamous => squamous papilloma, squamous cell carcinoma

glandular => adenoma, adenocarcinoma

transitional => transitional papilloma, transitional cell carcinoma

229
Q

benign + malignant histological neoplasms

A

benign for both = extremely uncommon

Lymphocytes => Lymphoma
Bone marrow =>

230
Q

teratomas

A

tumours derived from germ cells and can contain tissue derive from all 3 for 3 germ cell layers

may contain mature and / or mature tissue and even cancers

231
Q

differences between benign and malignant tumours

A

invasion => direct extension into adjacent connective tissue and /or other structures

metastasis => spread via blood vessels etc to other parts of body

differentiation => architecture of the tumour compared to architecture of the tissue

growth pattern

232
Q

by which routes do tumours spread

A

direct extension
haematogenous => via blood vessels
lymphatic => via lympg
transcoelomic => via seeding of body cavities
perineural => via nerves

233
Q

how do we assess tumour spread (staging)

A

tnm system

t = tumour: tumour size or extent of local invasion
n = nodes: number of lymph nodes involved
m = metastases: presence of distant metastases

234
Q

grade vs stage

A

grade = how differentiated is the tumour

stage = how far as the tumour spread

pom last minute stuff (4 decks)

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