IMMS Flashcards
1
Q
Mitosis
A
Produces two genetically identical daughter cells
Prophase, prometaphase, metaphase, anaphase, telophase
2
Q
Prophase
A
Nuclear membrane starts to disintegrate
Chromatin condenses into chromosomes
Chromosome microtubules move to poles
3
Q
Prometaphase
A
Nuclear membrane dissolves
Spindle fibres form (microtubules) and attach to centromere
4
Q
Metaphase
A
Homologous chromosomes line up down midline
5
Q
Anaphase
A
Chromatids pulled to opposite piles as spindle fibres contract
6
Q
Telophase
A
Nuclear membrane reforms
Chromosomes condense into chromatin
Spindle fibres disintegrate
7
Q
Cytokinesis
A
Cytoplasm divides
8
Q
Telomere
A
Region of receptive nucleotide sequences at end of chromosome for protection
Get shorter with each division
Built back with telomerase - enables unlimited cell division in cancer
9
Q
Centrosome
A
2 centrioles, each made of microtubules - cell structure and separate chromatids
10
Q
Meiosis
A
Produces 4 haploid cells haploid cells from two divisions ( only occurs in gametes )
Prophase 1 - crossing over
Metaphase 1&2 - independent segregation
PMAT -> PMAT ( NO INTERPHASE - not a cycle)
11
Q
Interphase
A
G1 - 2 x organelles
S - 2 x DNA & histones
G2 - chromosomes condense
Mitosis
12
Q
Karyotyping
A
Full set of metaphase chromosomes
13
Q
Heritability
A
% of an aetiology due to genetics - concordance of MZ twins
14
Q
Allelic polymorphism
A
> allele for gene in population, most common is SNP
15
Q
Locus heterogeneity
A
Variants in different genes
16
Q
Allelic heterogeneity
A
Variants in same genes
17
Q
Allelic homogeneity
A
Same variant in same gene
18
Q
Acquired
A
1 malignant tissue in life, not heritable
19
Q
Constitutional
A
All body cells including gonads - heritable :
De novo in gametogenesis or inherited
20
Q
Haploinsufficiency
A
Single wt allele not sufficient to produce wt phenotype
21
Q
Variable expressivity
A
1 genotype -> range of phenotypes ( severity)
22
Q
What percentage of our DNA is coding
A
1.5%
23
Q
Longest and shortest chromosomes
A
;
N1 = longest
N22 = shortest
24
Q
Robertsonian chromosomes
A
13,14,15,21&22
They lack a short arm (p arm)
Can be involved in specific types of translocation
25
The human genome
All of the genes and non coding DNA in the human body
26
Nucleosome
Eight his tone proteins around which DNA wraps 1.65 times
27
Chromatosome
A nucleosome plus the H1 histone
28
Genomes in the body
Germline - in sperm and eggs
Somatic - found in every other tissue
Mitochondrial- only found within the mitochondria
Only changes in the germline or mitochondrial genome can be passed from patent to child
29
Chromosome translocation
Part of one chromosome on another
Balanced - no loss of genetic material so person is healthy
Unbalanced - loss or gain of genetic material which can cause a human disease
30
Mutagenesis ( mutagen)
Alteration to the genomic code by exposure to a substance
Can be in the womb or post-natal ( e.g. in carcinogenesis)
31
Teratogenesis ( teratogen)
A damaging effect on embryonic/foetal development by an exposure to a substance
Different mechanisms : virus causing cell death, toxin interrupting blood supply
Some teratogens are also mutagens
32
Monogenic (Mendelian)
Mutation in a single gene is sufficient to cause disease
33
Somatic disease
Disease causing mutations are found in the affected tissue ( cancer)
34
Mitochondrial
Disease is caused by mutations in the mitochondrial membrane
35
Malformation
Intrinsic issue with development of an organ/tissue - commonly genetic
Minor - more than 2 then you should consider an underlying genetic condition
Major - should consider an underlying genetic condition
36
Deformation
Extrinsic factors impinge upon development of an organ (e.g.compression) - less commonly genetic
37
Autosomal dominant inheritance
Disease occurs in the heterozygous state ( one gene abnormal variant and one gene is normal)
38
Recurrence risk file autosomal dominant inheritance
Affected person has a 1/2 chance of having an affected child
39
Variable expressivity
People with the same gene variant can have a wide range of symptoms or physical features
40
Autosomal recessing inheritance
Disease occurs in homozygous state ( genetic variant in both copies of a gene )
Tends to be loss of function
41
Cystic fibrosis
Commonest recessive condition affecting Northern Europe population
Incidence - 1 in 2500
Carrier frequency - 1/25
CFTR gene on chromosome 7
42
Carrier frequency of sickle cell
1/10
43
Carrier frequency of Tay-sachs disease
1/30
44
Carrier frequency of congenital adrenal hyperplasia
1/35
45
Carrier frequency of Connie in-26 (deafness)
1/30-40
46
Penetrance
Percentage of individuals who have a variant in a certain gene who develop a medical condition because of it
Not everyone with a gene variant will develop the medical condition
47
Age related penetrance
The percentage of individuals who have a variant in a certain gene who develop a medical condition at a given age
48
Anticipation
A genetic condition manifests in successive I. Generations earlier with more severe symptoms
49
De novo mutations
The disease causing genetic variant occurs in either the spermicide or the egg
An u affected parent has a child with an autosomal dominant condition
50
X-linked recessive
Females are uaffected carriers, only males are affected
51
X-linked recessive
Females are unaffected carriers, only males are affected
52
X-linked dominant
Both males and females are affected
53
Male-male transmission
An affected man having an affected son.
If this happens in a family tree it means that the condition is not x-linked
54
Duchenne muscular dystrophy can
Mutation in the dystrophin gene on the x-chromosome
Absence if dystrophin protein in skeletal muscle
Limb weakness in males
Eventual use of a wheelchair
55
Skewed x-inactivation
80% of cells show preferential inactivation of one x-chromosomes ( should be around 50:50)
Can do on blood or affected tissue ( e.g. muscle)
56
Non-Mendelian inheritance
A disease is not explained by a dominant, recessive or x-linked mode of inheritance
57
Multifactorial inheritance
More than one factors causes trait Combination of genetic and environmental. Main cause of disease in developed countries. E.g. spina bifilar cleft palate, diabetes, schizophrenia
Risk of condition in relatives ( greatest for first degree relatives) of an affected individuals is dramatically higher than the general population
58
Somatic mosaicism
The accumulation of genetic variants in somatic cells after fertilisation. It may develop at any point after fertilisation, including adult life.
59
Germline mosaicism
Also known as gonadal mosaicism, this is the presence of two populations of cells within the gonad that differ genetically. (some gametes have a genetic variant and some do not )
60
Mosaic
Not every cell in a organism has the same genetic code
61
Mitochondrial disease
Symptoms occur because of a lack of energy (ATP) to drive cellular functions). All of our mitochondria are derived from our mother. A male with a mitochondrial disorder cannot have an affected child. Only ova are large enough to contain significant numbers of mitochondria.
The greater proportion of mutant mitochondria the more likely disease.
62
Homoplasmy
All mitochondria in call have same genetic code
63
Heteroplasmy
Certain proportion of mitochondria in a cell has a genetic variant
64
Imprinting disorders
All have two copies of each autosomal gene. For certain genes either the maternal or paternal copy is “switched off” these are printed genes.
Disease can be caused when imprinting is altered and genes are “switched on “ or “switched off“ inappropriately.
65
Inframe change of nucleotides
Multiples of three. Lose or gain single amino acid
66
Out of frame nucleotide insertion or deletion
Leads to formation of premature stop codon. Nonsense mediated decay
67
Single nucleotide variants
Change of one nucleotide ( wild-type) to another nucleotide (mutant)
Synonymous ( no alteration to protein)
Non-synonymous ( alters protein)
68
What suggests a variant is pathogenic?
The variant is found in several people in the family who have the disease ( segregation)
69
What suggests a variant is benign ?
The variant is found in an unaffected parent.
The variant is found commonly in healthy populations
computational tools predict the variant has no effect on gene function
70
Predictive genetic testing
Individual without symptoms requests test for highly penetrant genetic variant causing a disease
71
Predictive genetic testing
Individual without symptoms requests tests for highly penetrant genetic variant causing a disease.
In mentally competent adults this can be seen to promote their autonomy.
Provided there is no evidence of coercion by a third party etc
72
Mitochondrial matrix
Site of the kerbs cycle
73
Mitochondrial crista
Site of electron transport chain and chemiosmosis
74
Mitochondrial inner membrane
ATP synthesis embedded allows flow of H+ from ETC for ATP synthesis
75
Mitochondria
Site of respiration and ATP formation
76
Site of protein synthesis
Ribosomes
77
Rough ER
Synthesis and processing of proteins
78
Smooth ER
Contains enzymes for lipid synthesis
79
Golgi apparatus
Processing and packing proteins
80
Cytoskeleton
Structural support and movement of materials
81
Nucleus
Contains genetic information and assembles ribosome subunits
82
Lysosomes
Contains acid hydrolyses for digestion and recycling
83
Peroxisomes
Fatty acid and ethanol oxidation, contains catalase
84
Phospholipid
Hydrophilic polar head
Hydrophobic non-polar fatty acid tail
85
What are the contents of a phospholipid belayer with a fluid mosaic model
Cholesterol - binds together phospholipids
Proteins - transporters
Glycolipids and glycoproteins - cell signalling
86
Functions of a phospholipid belayer with a fluid mosaic model
Partially permeable membrane
Site of membrane receptors
Regulates what enters and exits cell
Barrier to separate intracellular contents from extra cellular contents
87
Protein types in a cell membrane
Consists of around 60% protein
Integral proteins - a-helix (recognition,receptors ), helical bundle ( enzymes, transporters, receptors ) and b-barrel ( transporters (channel proteins))
Peripheral proteins - ( enzymes, anchorage, transporters (carriers))
88
Autocrine communication
Messenger molecules bond with receptors in the cell where they are produced
E.g. chemical/secondary messages
89
Paracrine communication
Messengers in ECF
E.g clotting factors, prostaglandins in childbirth, inflammatory mediators
90
Endocrine communication
Secretions into blood
E.g. insulin
91
Positive feedback
Amplification of signal
E.g. clotting cascade, oxytocin and labour
92
Negative feedback
The basis of homeostasis
E.g. the majority of endocrine hormones
93
3 types of hormones
Peptide, steroid, amino-acid derivative
94
Peptide hormones
Made from short chain amino acids
Stored in cell and releases when needed/signalled
Binds to receptor on membrane
Produces a quick response via a secondary messenger cascade
E.g. insulin, growth hormone, TSH, and ADH
95
Steroid hormones
Synthesised from cholesterol,
Different enzymes modify molecules to produce a variety of hormones.
Can’t dissolve in water
Can dissolve in lipids
Produce a slow response as directly affects dna
96
Amino acid derives hormones
Synthesised from tyrosine, acts in same way to peptide
E.g. adrenaline, thyroid hormones
97
Metabolism
The sum of the chemical reactions that take place within each cell
Chemical reactions occur in sequence
98
Via what pathways are diary components metabolised
Biosynthetic
Fuel storage
Oxidative processes
Waste disposal
99
Anabolic
Synthesis larger molecules from smaller components
100
Catabolic
Break down larger molecules into smaller components
101
Catabolism
Provides energy from fuel molecules via the ATP cycle
102
BMR rough estimate
= 1 kcal / kg body mass / hour
103
What factors lower bmr
Age
Sex
Dieting/ starvation
Hypothyroidism
Decreased muscle mass
104
What factors raise bmr
BMI
Hyperthyroidism
Low ambient temp
Fever/infection/ chronic disease
105
Basal metabolic rate
Energy needed to stay alive at rest
Energy used for :
Respiration
Cardia contraction
Biosynthetic processes
Tissue repair and regeneration
Io gradients across cell membranes
106
Malnutrition
Sate of nutrition with a deficiency, excess or imbalance of energy, protein or other nutrients causing measurable adverse effects ( on tissue, body shape / size / composition, body function and clinical outcome.
107
Starvation
Overnight fast
Drop in insulin secretion
Glycogenolysis
Brain requires approx 150 g glucose a day
After an overnight fast, liver has about 80 g glycogen
Longer fasts necessitate gluconeogenesis ( make glucose from non-CHO sources)
108
Gluconeogenesis
Drop in insulin secretion
Rise in cortisol secretion
Gluconeogenesis uses :
Lactate
Amino acids ( muscle, intestine, skin breakdown)
Glycerol ( fat breakdown)
Liver creates keystones from fatty acids
109
The prudent diet
5 + servings of fruit/ vegetables
Base meals around starchy carbohydrates
No more than 5% energy should come from free sugars
0.8g/kg/ day protein
110
Oxidative metabolism
Linked pathways for breaking down nutrients to generate energy
111
Glycolysis
Breakdown of glucose inside cells
112
Gluconeogenesis
Synthesis of new glucose molecules form non-carbohydrate precursors ( e.g. lactate) in hepatocytes
113
Glycogenolysis
Conversion of excess glucose to glycogen, it’s storage form in hepatocytes and muscle tissues
114
ATP
The currency of metabolic energy
A high energy molecule composed of adenine ( purine base), ribose and three phosphate groups
115
Where and why does glycolysis occur
Occurs in cytosol under anaerobic conditions
An emergency energy producing pathway when oxygen is limiting
- RBCs and exercising skeletal muscle
Generates precursors for biosynthesis
116
Glycolysis - overview
One molecule of glucose is broken down to produce :
2 molecules of pyruvate ( C3H4O3). 2 NADH + H+ and 2ATP
117
Nucleus
Contains dna in the form of chromatin ( tightly wound around histone proteins )
118
Heterochromatin
Tight coils, repressed
119
Euchromatin
Loose coils, expressed
120
Mitochondria
ATP synthesis
121
SER
Membrane lipid synthesis, protein storage
Phase 1 detoxification
122
RER
Increases ribosomes ( protein synthesis)
123
Golgi
Cis - receives protein/lipid vesicles
Medial - adds sugars to these
Trans - package modified molecules into vesicles, exocytosed
Perinuclear hoff = plasma cells’ golgi; otherwise hard to see in other cells
124
Lysosomes
Degrades protein and cell autolysis
Ph 5 maintained by H+/K+ ATPases
125
Perioxisomes
Beta oxidation of fatty acids
Produces (znd destroys ) h2o2
Removes H from lipid/ alcohol/ toxic substances
126
Membrane protein carriers
Uniport - single substance
Glucose via glut-1
Passive
Antiport - two substances in opposite directions
3na+/2k+ ATPase
Energy from atp hydrolysis
Symport - two or more substances in the same direction
Na+/glc nutrient transport
Indirectly from atp hydrolysis
Ion gradient used
127
G coupled receptors
Extracellular binding activates transduction pathway internally
Cascade of internal reactions
128
Membrane channel proteins
Ligand gated ( depends on ligand binding to open )
Voltage gated
Mechanical, gated ( open when stretched)
129
Tight cell junctions
No passage
Cells sealed like a sheet
E.g. in gi tract, BBB
130
Adherins
Adjacent actin ( smaller) bundles of cells joined
131
Desmosomes
Adjacent intermediate filaments ( bigger) joined
132
Gal junctions
Allow adjacent cell passage of ions ( from cell to cell )
Key in myocardium contraction ( contracts as a synctium - need all to contract at the same time)
133
Hemidesmosomes
Intermediate filament to extracellular matrix
134
Focal adhesion
Actin to extracellular matrix
135
Diffusion and osmosis
Down conc gradient
136
Fac diffusion
Down conc gradient with protein
137
Active transport
Primary - na+-k+ atpase pumps
Secondary - indirect ; cotransport
138
Exocytosis
Vesicles bud off csm ( too big / hydrophilic for diff)
139
Endocytosis
Intake of molecules in phagosome vacuole
1. Phagocytosis - eating, engulfing whole cells
2. Pinocytosis - drinking, engulfing dissolved.
3. Receptor mediated
140
Three modes of homeostasis communication
Autocrine - acts on the same cell, secretion into ecf
Paracrine - secretion into ecf, acts on neighbouring cell
Endocrine - secretion into blood, acts in distant cell ( “target”)
141
Peptide hormones
Made from several aa
Water soluble ; directly in blood e.g. adh, insulin
Binds to csm surface
Fast acting
Pre-made and stored
142
Steroid hormones
Made from lipid cholesterol
Lipid soluble ; transport proteins in the blood
Diffuses through csm
Slow acting
Not pre-made
E.g. oestrogen, testosterone
143
RAAS ( renin angiotensin aldosterone system )
Activated when there is drop in BP ( Juxtaglamerular cells in Afferent arteriole in the kidney)
Or drop in Nacl ( detected by macula dense cells of the distal convoluted tubule ) x renin release from justaglameular cells
Angiotensinogen - ( by renin) - angiotensin 1 - ( ace) - angiotensin II - ADH, aldosterone, sympathetic NS
144
Osmolarity
Conc. / litre solution
145
Osmolality
Con./ kg solution
146
Oncotic pressure
Albumin pressure on capillary wall keeping fluid in
147
Osmotic pessure
Pressure exerted by pure solvent on solution needed to prevent inward osmosis ( solvent -> solution )
148
Hydrostatic pressure
Fluid pressure wants to move out of capillary
149
Glycolysis regulation
1. Hexokinase activity controlled by ( G6P)
2. PFK allostencally
- effected by AMP ( MORE AMP = MORE PFK ACTION )
- inhibited by ATP
150
Two glycolysis steps that produce ATP
1-3 bisphosphate - 3 phosphoglycerate
Phosphoenol pyruvate - pyruvate
