IMMS Flashcards
1
Q
Where in the cell is DNA located?
A
Nucleus and Mitochondria
2
Q
Describe the structure of DNA
A
DNA is a filamentous, helical structure formed by two antiparallel polynucleotidic chains joined by pairing between their bases
Adenine –> Thymine (2 bonds)
Guanine –> Cytosine (3 Bonds)
DNA coils around histone proteins to form nucleosomes, then coils again into supercoils (solenoid) forms chromatin and then again into chromosomes
3
Q
How many chromosomes do humans have?
A
46 - 22 autosome pairs and the sex chromosomes (XY)
4
Q
Describe the structure of a chromosome
A
Long Q arm and a short P arm separated by a central centromere
5
Q
What dyes can be used In chromosome identification?
A
Giesma = G banding Quinacrine = Q banding
6
Q
What is the purpose of mitosis?
A
Replace dead cells
Growth
Produce 2 daughter cells genetically identical to the parent cell
7
Q
What happens in the S phase of the cell cycle?
A
DNA replication
Centrosome Replication
8
Q
What happens in Prophase?
A
Chromatin condenses into chromosomes
Centrosomes nucleate microtubules and move to opposite poles of the cell
9
Q
What happens in Prometaphase?
A
Nuclear membrane breaks down and the microtubules invade the nuclear space and attach to chromatids
10
Q
What happens in metaphase?
A
Chromatids attached to microtubules line up along the equatorial plate (Metaphase plate)
11
Q
What happens in Anaphase?
A
Sister chromatids separate and are pulled to opposite poles of the cell as microtubules shrink
12
Q
What happens in telophase?
A
Nuclear membrane reforms and the chromosomes unfold into chromatid
Cytokinesis begins
13
Q
What is the clinical relevance of mitosis histology
A
Is cancer malignant or benign
Grade malignant tumour
Detect chromosomal abnormalities
Drugs to slow mitosis
14
Q
What drugs can be used to affect mitosis?
A
Stop spindle formation (Taxol and Vinca alkaloids (Vinblastine and Vincristine))
Stop spindle pole formation (Ispinesib)
Prevent Anaphase (Colchinine)
15
Q
How does meiosis differ from mitosis (4 things)
A
- Only occurs in gametes
- Recombination of genetic material causing diversity
- 2 divisions
- produces 4 haploid daughter cells
16
Q
Describe what happens in Meiosis
A
Start with parent cell that is 2M. DNA replicates and recombinates to produce a 4M cell which divides to produce to daughter 2M cells. These then divide further to produce 4 daughter cells that are M and are genetically different
17
Q
What is crossing over and when does it occur?
A
Produces recombinant chromosomes which carry genes from different parents - this occurs in prophase I
18
Q
Describe sperm production
A
Primordial cells are converted into spermatogonia via lots of mitoses in a process that takes 60-65 days
Cytoplasm divides equally
19
Q
Describe the production of egg cells
A
Primordial cell –> 30 mitoses –> Oogonia
The meiotic process begins in utero but is suspended part way through Meiosis I. Meiosis I is completed at ovulation and Meiosis II is completed at fertilisation.
Cytoplasm divides unequally into one 1 egg with all the cytoplasm and 3 polar bodies with no cytoplasm that apoptose
20
Q
What is non-dysjunction?
A
Failure of chromosomes pairs to separate in meiosis 1 and failure of sister chromatids to separate in meiosis 2
21
Q
Describe what happens to cause downs syndrome
A
Abnormality of trisomy 21 - non dysjunction causes one cell to have no chromosome 21 and one cell to have 2 chromosome 21
22
Q
What is gonadal mosaicism?
A
mutation arose in one of the stem cells which ultimately generates eggs or sperm then more that one egg or more than one sperm could contain the new mutation incidence
increases with increasing paternal age - most common in linked and autosomal dominant conditions
23
Q
Define genotype
A
Genetic constitution of an individual
24
Q
Define phenotype
A
Appearance of an individual (physical, biochemical and physiological) which results from interaction of environment and genotype
Characteristic that can be described or measured
25
Define allele
One of several alternative forms of a gene at a specific locus
26
Define polymorphism
Frequent hereditary variations at a specific locus
27
Define Homozygous
Both alleles at a locus are the same
28
Define Heterozygous
Alleles at a locus are different
29
Define Hemizygous
Only one allele refers to the locus on an x-chromosome in a male
30
Describe autosomal dominant inheritance and draw a diagram
Manifests in the heterozygous state with only one pathogenic variant required
31
Describe autosomal recessive and draw a diagram
Manifests in the homozygous state with the normal functioning gene compensating for the pathogenic variant - 1in4 chance of having disease and 2in4 chance of being carrier
32
Describe X-linked recessive and draw a diagram
Caused by pathogenic variants on the x-chromosome
33
What does tRNA do
Carries amino acids to ribosomes and ensures they are in the correct position - each tRNA only carries one AA at its 3' end so there are 20 types
34
How is DNA made accessible to transcription factors to enable replication?
Heterochromatin inaccessible to transcription factors --> Recruit histone acetyltransferases --> Recruit chromatin remodelling complexes --> Recruit DNA demethylases --> Euchromatin = accessible to transcription factors
35
Define an out of frame deletion variant
Deletion of one or two bases causes reading frame to shift so Amino acids change and so does protein sequence
36
Define an in frame deletion variant
Loss of 3 bases resulting in loss of an amino acid and formation of a truncated protein ie. dystrophin truncation in milder Becker muscular dystrophy = less severe than out of frame
37
Define a splice site variant
Affects accuracy of intron removal - normal splice acceptor site is 4 base pairs ie. CCAT - however if A changed to C then enzyme doesn't recognise so no cut made and abnormal protein is translated
38
Define a non-sense mutation
Out of frame deletion of a single base pair causes the codon to change to a stop codon at the deletion site or further along
39
Define a mis-sense mutation
Single base substitution changes amino acid in the protein sequence - may or may not be pathogenic
40
Give three examples of try-nucleotide repeat disorders
Huntington's - CAG
Myotonic Dystrophy - CTG
Fragile X - CGG
41
Define allelic heterogeneity
Lots of different variants of one gene ie. cystic fibrosis
42
Define locus heterogeneity
Variants of different genes give the same clinical condition ie. hypertonic cardiomyopathy
43
Define autosome
Any chromosome other than the sex chromosomes that occurs in pairs in diploid cells
44
What are the characteristics of an autosomal recessive disorder
```
Manifests in the homozygous state
Males and females affected equally
Affects individuals in only one generations
If both parents are carriers
1/4 has disease
2/4 are carriers
1/4 unaffected but if one parent affected...
all 4 children will be carriers
```
45
What is the carrier frequency of cystic fibrosis and where does the mutation occur?
1/25 with mutations occurring in the CFTR gene located on gene 7q31.2
46
Define Consanguinity
Reproductive union between two relatives
47
Define Autozygosity
Homozygosity by descent - inheritance of the same altered allele through two branches of the same family
48
What are the characteristics of autosomal dominant inheritance?
Manifest in heterozygous state
Male and female equally affected
Passed from both sexes to both sexes
Penetrance and variability
49
Define Penetrance
Percentage of individuals with. specific genotype showing the expected phenotype
50
What are the characteristics of X-linked inheritance
Gene carried on the x-chromosome
Usually transmitted through unaffected females
Usually only males affected
No male to male transmission
51
What are the 3 types of numerical chromosome abnormality?
Trisomy - gain of 1 chromosome
Monosomy - loss of 1 chromosome
Polyploidy - Gain of a whole chromosome set
52
What are the 4 types of structural chromosome abnormality?
1. Translocation - exchange of material between chromosomes
2. Inversion - part of a chromosome is chopped out, inverted and reinserted into itself or another chromosome
3. Duplication - part of a chromosome is duplicated and reinserted
4. Deletion
53
What is triploid karyotype?
3 of each chromosome = incompatible with life
if extra chromosome comes from mother = intrauterine malformation - if comes from paternal side = placenta becomes malignant
54
What disease is associated with deletion at the Q arm of chromosome 15?
If paternal = Prader Willi
| if maternal = Angelman Syndrome
55
Define multifactorial disease
Disease that are the result of a combination of genetic and environmental factors
56
What studies can be used to determine if a disease has a genetic component?
Family
Twin
Adoption
57
Describe a family study
Compare the incidence of a disease amongst the relative of an affected individual with the general population
58
Describe twin study
Compare monozygotic (identical) and dizygotic (non identical twins - if disease has a genetic component the concordance rate should be higher in monozygous
59
Define heritability
Proportion of the aetiology that can be attributed to genetic factors as opposed to environmental factor
60
List environmental factors that may act on embryogenesis
Drugs and chemicals
Maternal infections
Physical agents (radiation)
Maternal illness (Diabetes)
61
List environmental factors that may act post natally
Obesity
Hormonal factors (pill)
Smoking
Recreational drugs
62
What are the 4 pathways of metabolism in the body
Storage - anabolic
Biosynthetic - anabolic
Oxidation - catabolic
Waste disposal - either
63
What are the dietary components?
Fuels, Essential Fatty Acids,
| Essential amino acids, Vitamins, minerals, water, xenobiotics
64
What are the dietary fuels
Carbohydrates
Lipids
Proteins
Alcohol
65
Where are dietary fuels stored?
1. Fat as triglycerides in adipose tissue (15kg)
2. Carbohydrate as glycogen in the liver (200g) and the muscles (150g)
3. Protein as muscle (6kg)
66
How much energy per gram is there from carbohydrates/protein/alcohol and lipids
```
Carb = 4kcal/g
Protein = 4kcal/g
Alcohol = 7kcal/g
Lipid = 9kcal/g
```
67
What is the main source of ATP during rest and low intensity exercise
Oxidative system primarily using carbohydrates and Fats - during high intensity exercise almost 100% derived from carbohydrates
68
When is protein used as an energy source?
During prolonged exercise (>90mins) and during periods of starvation
69
Define basal metabolic rate
Every required to maintain non exercise bodily functions ie. respiration, heart muscle contraction, biosynthetic processes, repair and regeneration of tissues and ion gradients
BMR = approx 1kcal/kg body mass/ hour
70
What factors decrease basal metabolic rate?
```
Age
Hypothyroidism
Gender
Diet and starvation
Decreased muscle mass
```
71
What factors increase basal metabolic rate?
```
Exercise
Hyperthyroidism
Low ambient temperature
Caffeine/stimulant intake
Body Weight
Pregnancy and Lactation
Fever/Chronic disease/Infection
```
72
What are the sources for gluconeogenesis?
Lactate
Amino Acids (Intestine, Muscle + Skin)
Glycerol (Fat breakdown)
Liver --> Ketone from fatty acids
73
Define malnutrition
State of nutrition with a deficiency, excess or imbalance of energy, protein or other nutrient that causes measurable adverse effects
74
What are the two essential fatty acids?
Omega-3
| Omega-6
75
What are the essential amino acids and how much do we need?
Need 0.8g/kg/day
| Lysine, isoleucine, leucine, threonine, valine, tryptophan, phenylalanine, methionine and histidine
76
What does vitamin B1 (Thiamine)?
Helps with energy production in the body
77
What does vitamin C do?
Helps to prevent cell damage and reduce certain cancers, heart disease and other diseases, collagen synthesis, protects from infections and increases the amount of iron the body absorbs
78
What does vitamin D do?
Increases the amount of calcium and phosphorus the body absorbs from foods and deposits calcium and phosphorus in bones, teeth making them stronger and healthier
79
What is the equation for the hydrolysis of ATP in ADP?
ATP + Water --> ADP + Pi + H+ +Heat
80
Where does glycolysis occur?
In the cytosol of the cell
81
What is the rate limiting factor in glycolysis?
Phosphofructokinase Enzyme
82
What enzyme catalyses the conversion of glucose to Glucose-6-phosphate? Where is it located?
Hexokinase (Form of glucokinase) found in the liver that acts when bloodstream glucose levels are high
83
What happens to the ADP produced in the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate?
ADP is converted to ATP and AMP by the action of Adenylate Kinase
84
What are the allosteric activators of phosphofructokinase?
AMP
| Fructose-2,6-Bisphosphate
85
What are the allosteric inhibitors of phosphofructokinase?
ATP
| Citrate
86
How does Fructose-2,6-bisphosphate allosterically activate PFK
Increase in glycolysis increases fructose-1,6-bisphosphate production which activates pyruvate kinase in the liver - increased insulin levels cause increased fructose-2,6-bisphophate levels and high glucagon levels reduce production
87
What is the fate of pyruvate in anaerobic and aerobic conditions?
```
Aerobic = enters Krebs cycle
Anaerobic = Lactate
```
88
Write an equation for the conversion of glucose to lactate in anaerobic conditions
Glucose + 2ADP + 2Pi --> 2 Lactate + 2ATP + 2H2O + 2H+
89
How many molecules of pyruvate are produced from one molecule of glucose-6-phosphate?
2
90
Aerobic oxidation of glucose to CO2 produces how many molecules of ATP?
30-32 mol of ATP per mol of glucose
91
What happens in anaerobic glycolysis and what is the ATP yield?
Lactate dehydrogenase oxidises NADH from glycolysis by converting pyruvate into lactate - produces 2 mol ATP per mole of glucose
92
What inhibits hexokinase?
Glucose-6P inhibits glucokinase action so glucose is not taken up and phosphorylated by cells unless glucose-6P enters a metabolic pathway
93
What is the function of glycolysis?
ATP production
Generates pyruvate as precursor for fatty acid biosynthesis
Provides precursors for synthesis of Amino acids and five carbon sugar phosphates
94
What can glucose-6P be used for?
Glycolysis
Other pathways
Pentose Phosphate Pathway
Glycogen Synthesis
95
Fructose-1,6-bisphosphate is cleaved into dihydroxyactone phosphate and glyceraldehyde phosphate by which enzyme
Aldolase
96
Which enzyme is responsible for the oxidation of glyceraldehyde 3-phosphate into 1,3-bisphosphate and what else is produced
glyceraldehyde-3-phosphate dehydrogenase and NADH
97
Which enzyme is responsible for the conversion of 1,3-bisphosphoglycerate into 3-phosphoglycerate
phosphoglycerate kinase
98
Which enzyme is responsible for the conversion of glucose 6P into fructose 6P
Phosphoglucose isomerase
99
Which enzyme is responsible for the conversion of 3-phosphoglycerate into 2-phosphoglycerate
Phosphoglycerol mutase
100
Which enzyme is responsible for the conversion of 2-phosphoglycerate into phosphenolpyruvate and what biproduct is produced?
Enolase and water
101
Which enzyme is responsible for the conversion of Phosphenolpyruvate to pyruvate
Pyruvate kinase
102
Write an overall equation for glycolysis
Glucose + 2ADP + 2Pi + 2NAD+ --> 2 Pyruvate + 2NADH + 2ATP + 2H20 + 4H+
103
How does AMP allosterically activate PFK-1?
Binding of AMP increases the affinity of PFK for fructose 6P
104
Write an overall equation for the TCA cycle
Acetyl CoA + GDP + 3NAD+ + 2H2O +FAD + Pi --> CoASH + GTP + 3NADH + 3H+ + GTP + FAD (2H)
105
Which enzyme catalyses the conversion of oxaloacetate to citrate
Citrate dehydrogenase
106
Which enzyme catalyses the conversion of citrate to isocitrate
Aconitase
107
Which enzyme catalyses the conversion of isocitrate to alpha-ketoglutarate
Isocitrate dehydrogenase
108
Which enzyme catalyses the conversion of alpha-ketoglutarate into succinyl CoA
Alpha-ketoglutarate dehydrogenase
109
Which enzyme catalyses the conversion of succinyl CoA into succinate?
Succinate thiokinase
110
Which enzyme catalyses the conversion of succinate into fumarate
Succinate dehydrogenase
111
Which enzyme catalyses the conversion of fumarate into malate
Fumarase
112
Which enzyme catalyses the conversion of malate into oxaloacetate?
Malate dehydrogenase
113
What is the is rate limiting step in the TCA cycle
Isocitrate dehydrogenase
114
What are the allosteric activators of isocitrate dehydrogenase
ADP
115
What are the allosteric inhibitors of isocitrate dehydrogenase
NADH
116
Describe the process of fat absorption
1. Bile salts emulsify fats forming micelles
2. Intestinal lipase break down TG's
3. FA's are taken up by intestine and converted to TG's
4. TG's combine with apolipoproteins and cholesterol to form chylomicrons
5. Chylomicrons enter bloodstream through lymphatic system
6. Lipoprotein lipase in capillary releases FA's and glycerol
7. FA enters cell and Is oxidised for use as fuel or esterified for storage
117
What are four reaction stages of B-oxidation
1. Oxidation
2. Hydration
3. Oxidation
4. Thiolysis
118
What enzyme catalyses the first oxidation stage of B-oxidation and what are the byproducts
Acyl CoA dehydrogenase
| FAD+ converted to FAD (2H)
119
What enzyme catalyses the hydration stage of B-Oxidation and what is required for this to occur?
Enolase Hydrate
| H2O
120
What enzymes catalyses the second oxidation step of B-oxidation and what are the byproducts
Hydroxyacyl CoA dehydrogenase
| NAD+ converted to NADH
121
What enzyme catalyses the thiolysis stage of B oxidation and what are the byproducts?
Thiolase
| CoA-SH converted to Acetyl CoA and Acyl CoA is produced
122
What factors affect the rate of ketogenesis?
Release of FA as more FA saturate TCA cycle so more Ketones produced
Glycerol-3-phosphate increases TG production so less ketones but decreased glycerol 3-P will increase TG production
Depends on levels of insulin and glucagon
123
What symptoms will diabetic patients with ketoacidosis present with?
Hyperventilation
| Vomiting
124
What are three effects of an insulin deficiency
1. Inhibition of glycolysis and stimulation of gluconeogenesis
2. Glycogen breakdown and inhibition of glycogen synthase
3. Increased lipolysis and FA production
These effects lead to hyperglycaemia and increased ketones production = diabetic ketoacidosis
125
Describe what happens in alcoholic acidosis?
Increased blood ethanol and depleted carbo and protein stores leads to impaired gluconeogenesis, increased glucagon and decreased insulin which increases lipolysis and FA production and increases ketone production
126
What are the physiological consequences of ketoacidosis
High O2
Low CO2
Low HCO3
Low Blood pH
127
Describe the properties of a channel membrane protein
Narrow aqueous pore
Selectivity based on size and charge
Passive process
Can be gated based on ligand or voltage
128
Describe the properties of a carrier membrane protein and describe the three different types
```
Have a specific binding site that will cause a conformational change
Can be active or passive
1. Uniport
2. Symport
3. Antiport
```
129
What are the types of membrane transport
Passive (Simple or facilitated)
| Active (Primary or secondary)
130
Describe primary active transport giving an example and a further example of when it goes wrong
Directly uses an ATP source ie. Na+/K+ATPase
ATP7B is a Cu2+ ATPase in the liver that transports copper into the bile - Wilsons disease causes copper deposits in the liver, brain and eyes
131
Describe secondary active transport giving an example and a further example of when it might go weong
Transport against a concentration gradient coupled to the movement of another ion downs its conc gradient ie. Na+/glucose cotransporter (SGLT1)
Less functional SGLT1 causes the glucose-galactose malabsorption
132
Where do steroid hormones bind?
Intracellular
133
Where do peptide hormones bind?
Cell-surface
134
Describe positive eugenics
Encouraging a group of individuals to reproduce
135
Describe negative eugenics
Discouraging a group of individuals to reproduce
136
Define homeostasis and the parameters that are controlled
```
Maintenance of a constant environment
Temp
pH
O2 Conc
Blood Pressure
Glucose
Energy production and demand
```
137
What are the three major cell communication systems
Endocrine
Nervous
Immune
138
What is autocrine signalling
Cell communicates with itself
139
What is paracrine signalling and give an example
Signal diffuses across gap between neighbouring cells and doesn't enter bloodstream
ie. AcH and Neuromuscular junctions
140
What is endocrine signalling
Cells talking to other cells elsewhere in the body
| ie. hormones entering the bloodstream
141
Describe the organisation of the endocrine system
Hypothalamus releases hormones which act on the anterior pituitary to release stimulating hormones which act on a target tissue directly or through an endocrine gland to affect a target tissue
142
What are the 6 hypothalamic hormones
```
Gonadotrophin releasing hormone
Growth hormone releasing hormone
Somatostatin
Thyrotropin releasing hormone
Corticotropin releasing hormone
Dopamine
```
143
What are the 6 main anterior pituitary stimulating hormones
```
Follicle stimulating hormone
Luteinising hormone
Growth hormone
Thyroid stimulating hormone
Prolactin
Adrenocorticotrophic hormone
```
144
What are the two main posterior pituitary hormones
Oxytocin
| Anti-diuretic hormone (Vasopressin)
145
Define what a hormone is and what the three main times are
A molecule that acts as a chemical messenger
Peptide
Steroid (from cholesterol)
Amino Acid (from tyrosine/tryptophan)
146
Give an example of a peptide hormone, amino acid hormone and steroid hormone
Peptide = insulin/growth hormone
Amino Acid = Adrenaline and thyroxine
Steroid = testosterone
147
What is the function of the smooth endoplasmic reticulum?
Site of lipid synthesis and some drug metabolism
148
What is the function of the golgi body?
Mediates protein sorting to specific sites
149
What is the function of the rough endoplasmic reticulum?
Protein synthesis
150
What is the function of ribosomes?
Translate mRNA into protein
151
Describe the structure of a phospholipid
Fatty acid tail are non polar and hydrophobic (either saturated or non sat)
Phospholipid head is polar and hydrophilic (either serine, choline or inositol
152
What is the plasma membrane permeable to?
Water, Gases (CO2, N2, O2) and small uncharged polar molecules (urea and ethanol)
153
What is the plasma membrane impermeable to?
ions (Na+/K+/Cl- and Ca2+
Charged polar molecule molecules (ATP, Glucose-6-phosphate)
Large uncharged polar molecules (Glucose)
154
What is an integral cell membrane protein
A protein that is embedded within the bilayer
155
What Is a peripheral cell membrane protein
A protein that is associated with the membrane
156
What are the constituents of the plasma membrane
```
Receptors
ATP driven transporters
Ion channels
Transporters
Adhesion molecules
Self: Non-self
```
157
What happens when pH and temperature of plasma membrane change?
Both extremes of pH will damage protein and inhibit cell function
Too cold and the proteins slow down and membrane becomes less fluid
Too hot and the proteins denature and membrane fluidity increases
158
Describe the distribution of water in the body
```
Total body water is 42L
28L Intracellular
14L Extracellular
Of this 14 L
3L is intravascular
11L is interstitial
```
159
What ion is the main contributor to ECF osmolality and volume?
Sodium
160
What Is the predominant ion in the ICF?
Potassium
161
Describe the pathways and volumes of water gain in the body
Food and drink = 2.2L/day
| Metabolic Production = 0.3L/day
162
Describe the pathways and volumes of water loss in the body
```
Insensible loss (Skin and lungs) = 0.9L/day
Urine = 1.5L/day
Faeces = 0.1L/day
```
163
What is normal plasma osmolality
275-295
164
Describe what happens during water deprivation/dehydration
| (Increase in ECF Osmolality) = rapid change
Water moves from the ICF to the ECF
ECF osmolality increases
ADH released from posterior pituitary = renal water retention
Stimulation of thirst centre in hypothalamus = increased water intake
165
What happens when ECF volume decreases?
Decreased renal perfusion detected by juxta glom causes renin release from kidneys. Renin converts Angiotensinogen from the liver to angiotensin 1 which is converted to angiotensin II by ACE from lungs
166
What are the effects of Angiotensin II
increased sympathetic activity
Tubular Na+, Cl- reabsorption and K+ excretion = water retention
Aldosterone secretion from adrenal gland
Arteriolar vasoconstriction to increase blood pressure
ADH secretion causing increased h2 absorption at collecting duct
167
What are the causes of water depletion?
```
Vomiting
Diarrhoea
Diuresis/Diuretics
Burns
Sweating
Reduced intake
```
168
What are the symptoms of dehydration?
```
Thirst
Dry mouth
inelastic skin
Sunken eyes
Raised haematocrit
Weight loss
Confusion
Hypotension
```
169
What happens when there is water excess in the body
Water moves from ECF to the ICF
ECF osmolality decreases so no stimulation of thirst centre
ADH secretion is inhibited leading to increased urine volume
Results in risk of cerebral over hydration
170
What are the consequence of water excess in the body?
Hyponatraemia
| Cerebral over hydration which causes headaches, confusion and convulsions
171
Define Oedema
Excess accumulation of fluid in the interstitial space
172
Define hydrostatic pressure
Pressure difference between the plasma and the interstitial fluid
173
Define oncotic pressure
Pressure difference between the plasma and the interstitial fluid caused by protein concentration
174
Define serous effusion
Excess water in a body cavity
175
What is the two main pathogenesis of oedema and serous effusion?
Impaired fluid reabsorption
| Increased fluid leakage into interstitial spaces
176
What are the 4 types of oedema?
Inflammatory
Venous
Lymphatic
Hypoalbuminaemic
177
Define transudate?
Fluid pushed through the capillary due to high pressure within the capillary
178
Define Exudate
fluid that leaks around the cells of the capillaries caused by inflammation and increased permeability of pleural capillaries to proteins
179
What are the causes of hypernatraemia?
Water deficit due to poor intake, osmotic diuresis or diabetes insipidus
Sodium excess due to mineralocorticoid excess
180
What are the causes of hyponatraemia?
Artefactual
Sodium loss due to diuretics and Addison's disease
Excess water due to Iv fluids or SIADH
181
What is the general formula for carbohydrates?
Cn(H2O)n
182
What is the difference between the structure of alpha and beta glucose?
In alpha glucose the OH group is below and in beta glucose the OH group is above
183
Describe a glycosidic bond
When a hydroxyl group of a monosaccharide reacts with the OH or NH group of another monosaccharide to form a glycoside
184
What are the constituents of Maltose
2 alpha glucose molecules
185
What are the constituents of sucrose
Alpha glucose and fructose
186
What are the constituents of lactose
Galactose B and alpha glucose molecule
187
Give three examples of polysaccharides
Starch (Amylose (Glu 1-4) and amylopectin (Glu 1-6)
Proteoglycans
Glycogen
188
How are phosphoacylglycerols formed?
Derived from phosphatidic acid
| FA are esterified to glycerol and phosphorylated at C3
189
What are sphingolipids formed from?
Ceramide
190
What molecule are steroids derived from?
Cholesterol
191
What are ecosanoids derived from and give examples
Synthesised for Eicosanoic acid and include prostaglandins
192
What are the constituents of a Nucleotide
Nitrogenous Base
Sugar
Phosphate
193
Which amino acid has a cyclic structure?
Proline
194
Which amino acids contain sulphur in their side chains?
Methionine
| Cysteine
195
What are the noncharged polar Amino acids
Methionine, cysteine, glutamine, serine and threonine
196
Which amino acids are negatively charged?
Glutamate
| Aspartate
197
Which amino acids are positively charged?
Arginine
Lysine
Histidine
198
What are the aromatic amino acids
Tyrosine
Tryptophan
Phenylalanine
199
Describe Van Der Waal Forces
Weak attractive interactions between atoms due to fluctuating electrical charges - important when macromolecular surfaces fit closely in shape
200
Describe hydrogen bonds
Interaction between oppositely charged dipoles due to partial charges on oxygen, nitrogen and fluorine molecules
201
Describe ionic bonds
Occur between fully or partially charged groups
202
Describe disulphide bonds
Covalent bonding between cysteine residues
203
Define the primary sequence of an amino acid
Linear sequence of amino acids linked by peptide bonds
204
Give 4 examples of super secondary structures
Helix turn helix
Beta alpha beta unit
Leucine zipper
Zinc finger
205
What factors influence the rate of a chemical reaction
```
Temperature
Concentrations of reactants
Catalysts
Surface area of the solid reactant
Pressure of gaseous reactants or products
```
206
Describe the structure of a chromosome
Two strands of sister chromatids joined by a central centromere
207
Describe the stages of the cells cycle?
```
G1 = growth and metabolism
S = DNA replication
G2 = Preparation for cell division
M = mitosis
```
208
Which enzyme opens up the DNA double helix
Helicase
209
What is the function of topoisomerase?
Unwinds supercoiled DNA t form uncoiled DNA
210
What are the functions of the plasma membrane?
Act as a semipermeable membrane
Host cell membrane receptors
Regulates what goes in and out of the cell
Separates the intracellular and extracellular contents
211
What are the differences between DNA are RNA?
DNA in nucleus, RNA in cyto
DNA double strand, RNA single
DNA deoxyribose, RNA ribose sugar
RNA bases exchange thymine for uracil
212
Define osmolality
Concentration of solutes in plasma per kilogram solvent
213
Define osmolarity
Concentration of solutes in plasma per litre of solution
214
Define the secondary structure of proteins
Local folding of polypeptide chain into helices or sheets
215
Define the tertiary protein structure
Three dimensional folding pattern of a protein due to side chain interactions
216
Define quaternary protein structure
Protein consisting of more than one amino acid side chain
217
What does H and E stain in the cell?
Haematoxylin stains nuclei blue
Eosin stains cytoplasm pink
Extracellular fibres stain pink
GAG do not stain
218
What does PAS stain for?
Sugars - stains magenta
| useful for GAG's in intestinal border
219
What does van giesons stain for and what colour?
Elastic
Stains brown for elastic stains
Collagen stains pinkish red
Muscle stains yellow
220
What does alcian blue stain for?
Mucins secreted by epithelial cells
221
Give an example of a small cell and its size
Lymphocytes 10micrometers in diameter
222
Give an example of a large cell and its size
Motor neurones 100 micrometers in size
223
What are the 6 types of cell
```
Rounded
Polygonal
Cuboidal
Columnar
Squamous (flattened)
Fusiform
```
224
What are the differences between metabolically active and dormant cells
Dormant cells are smaller and have less cytoplasm and smaller nuclei whereas active cells are larger and have a nucleoi
225
Which cells have life span of days, months, years, nearly whole life and lifetime?
Days - cells lining gut
Months - Skin, blood and connective tissue
Years - bones and tendons
Near WL - Skeletal muscle
WL - nerves, brain, cardiac muscle and germ cells
226
What are the membrane organelles
Nucleus, mitochondria, lysosomes, peroxisomes, ER and golgi
227
What are the non membrane organelles
Ribosomes, centrosomes, centrioles and basal bodies
228
Describe the structure of the nucleus
Contains cellular DNA and nucleolus
Measures 5-10um diameter
Double membrane that contains pores
229
Describe the structure of the double membrane of the nucleus
Inner membrane contains nuclear lamins which are network of protein filaments that maintain spherical shape
Outermembrane binds perinuclear space which is continuous with lumen of ER
230
What os the size and function of the nucleolus?
1-3 microns in diameter and functions as the site of ribosomal RNA formation
231
What are the three areas of the nucleolus?
```
Pars Amorpha (Pale areas)
Pars Fibrosa (Dense stain areas)
Pars Granulosa (Granular regions)
```
232
Which forms of chromatin is light stained and is actively transcribed?
Euchromatin
233
Which form of chromatin is dense stained and highly condensed so transcriptionally inactive?
Heterochromatin
234
What processes occur in the outer mitochondrial membrane?
Lipid synthesis
| Fatty acid metabolism
235
What processes occur in the inner mitochondrial membrane?
Respiratory chain ATP production
236
What process occurs in the mitochondrial matrix?
TCA cycle
237
What process occurs in the mitochondrial inter membranous space?
Nucleotide phosphorylation (ADP --> ATP)
238
What is the function of the RER?
Site of protein synthesis
| Produces phospholipids and proteins of the plasma membrane
239
What is the function of SER?
Site of membrane lipid synthesis and processes synthesised proteins
240
What is the function of the Golgi apparatus?
Synthesises steroids and other lipids
Detoxifies alcohol and drugs
Processes macromolecules synthesised in the ER and stores them
241
Describe the location and function of the cis face of the Golgi apparatus
Nuclear facing
| Receives the transport vesicles from the smooth ER and phosphorylates some proteins
242
Describe the location and function of the medial golgi
central part of golgi
| Forms oligosaccharides by adding sugar to lipids and peptides
243
Describe the location and function of the trans golgi apparatus
Outer face
Proteolysis
Sorts molecules into vesicles that become lysosomes, migrate to plasma mem and fuse or become secretory vesicles that store protein for later
244
What are the 5 types of vesicles
```
Cell surface derived pinocytic and phagocytic vesicles
Golgi derived transport vesicles
ER derived vesicles
Lysosomes
Peroxisomes
```
245
What is the function of lysosomes?
Intracellular digestion
| H+ ATPase on membrane creates low internal pH
246
What are the function of peroxisomes?
Small (0.5-1 microns)
| Produced by ER and use molecular oxygen to oxidise organic molecules
247
What is the function of the cytoskeleton?
Determines the cell shape, structure, organises cell contents, directs movement of materials within the cell and contributes to cell movements as a whole
248
What are the properties of microfilaments?
Smallest (5nm)
Made of actin
Forms branching mesh on inner surface of cell membrane to maintain shape
249
What are the properties of microfilaments?
25nm diameter
Made from tubulin
Scaffold for mitosis and meiosis radiating from centrosome
250
What are the properties of intermediate filaments?
10nm diameter
6 different types of proteins
Anchored to transmembrane proteins and spread tensile forces throughout proteins
251
What are the 6 types of intermediate filament and where are they localised?
```
Cytokeratins = epithelial cells
Desmin = Myocytes
Glial Fibrially acid protein = astrocytic glial cells
Neurofilament protein = neurones
Nuclear laminin = Nuclei of all cells
Vimentin = mesodermal cells
```
252
What is lipofuscin?
membrane bound orange-brown pigment
Peroxidation o lipids in ider cells
Common in heart and liver
253
What are the constituents of the extracellular matrix?
Fibrillar proteins (Tendons - collagen and elastin)
Glycosaminoglycans
Inorganic salts as solids
254
What does a pink stained (Acidophilic) cytoplasm indicate?
accumulations of organelles usually mitochondria
255
What does a blue cytoplasm indicate?
Presence of cytoplasmic RNA in ribosomes and active protein production
256
What are the three functions of epithelia?
Protection - skin
Absorption - gut
Secretion - pancreas, liver and GIT
257
Describe the organisation of simple squamous epithelia and its function
Single layer of cells on basement membrane, parallel oval nuclei - absorption and secretion
258
Describe the organisation of stratified (compound) epithelia and where it is found?
Two or more layers of cells on basement membrane - protection
Areas of body that experience frictional and abrasive forces ie. skin, mouth, throat, oesophagus and vagina
259
Where are simple squamous epithelium found?
```
Lining of blood vessels (Endothelium)
Outside lungs (Mesothelium)
Abdominal Organs (Peritoneum)
Alveoli - form barrier between air and blood
```
260
Describe the organisation of simple cuboidal epithelium and where it is found?
Single layer of cells with same heigh and width
Central spherical nuclei
Found in ducts and glands including sweat, salivary and pancreas
ducts in exocrine glands
261
Describe the organisation of simple columnar epithelium and where it is found?
Single layer, taller than are wide, spheroidal nucleus - can be ciliated or microvilli
Lines the stomach, intestines and uterus
262
What lies at the boundary of blue/purple living cells and dead pink keratinising layers
Layer of blue keratohyaline granules
263
Describe pseuostratified epithelium and where it is found
Single layer of cells of variable height with all cells in contact with basement membrane
Lines conducting airways
264
Describe urothelium and its location
Looks stratified but there is a surface layer of umbrella cells not in contact with the basement membrane
Lines bladder, ureter and renal pelvis
265
What proteins is the basement membrane composed of?
Fibronectin and collagen IV
266
What are the three types of epithelial junction?
Occluding (tight)
Desmosomes
Gap
267
Describe an occluding junction
Band like fusions that prevent diffusion between cells
268
Describe a desmosome and its function
Plaques that form physical junctions between cells by connecting adjacent cytoskeletons
Spread mechanical forces across cells
269
What is the function of a hemidesmosome?
Connect intermediate filament network of cells to extracellular matrix
270
Describe gap junctions
Electrical junctions that permit transfer of small molecules and electrically couple adjacent cells
271
Describe the properties you would see in a protein secreting epithelial cell
Large nuclei and abundant RER - blue colouration with H and E stain
272
Describe the properties you would see in a mucin secreting epithelial cell
Expanded golgi system
273
Describe the properties you would see in a steroid producing epithelial cell
Extensive smooth ER
274
Define holocrine
Secrete by releasing cells
275
Define apocrine
Secrete by budding
276
What are the properties of amorphous material?
High molecular weight
Strongly hydrophilic
Negatively charged
Enables retention of water
277
What secretes GAGs?
Mainly fibroblasts but also epithelial cells, muscle, cartilage and bone
278
Describe fibrous connective tissue
Contains large numbers of fibres including collagen, elastin and reticulin
279
Describe loose irregular fibrous connective tissue
Contains few randomly orientated fibres
280
Describe dense irregular fibrous connective tissue
Contains large number of fibres with little amorphous material
281
Describe fatty connective tissue
Contains mainly fat cells with intervening blood vessels particularly capillaries
282
What is the origin of connective tissue cells
Mainly undifferentiated mesenchymal cells forming fibroblasts, adipose, chondroblasts and osteoblasts and from haemopoietic stem cells (monocytes, macrophages, lymphocytes and mast cells
283
What are the constituents of connective tissue
```
Cells (fibroblasts/cytes, adipose
Visible fibres (Collagen, elastin, reticulin)
Ground substance (Proteoglycans, glycosaminoglycans, laminin, fibronectin
```
284
Where would you find type 1 collagen?
Skin, teeth, bone and organ capsules
285
Where would you find type 2 collagen?
Cartilage
286
Where would you find type 3 collagen?
Liver, bone marrow and spleen (known as asreticulin)
287
Where would you find type 4 collagen?
Basement membrane
288
Where would you find type 5 collagen?
Placenta
289
Describe the formation of collagen fibres
Fibroblasts secrete tropocollagen subunits with are assembled extracellularly to give rise to individual fibres
290
Where is brown fat most likely to be found?
across back and shoulders of Neonates
291
Describe the structure of cartilage
Chondroblasts derived from mesenchymal stem cells become embedded in GAG matriculates contain glycosaminoglycans (Hyaluronic acid) and proteoglycans (Condroitin sulphate and keratin glycan) and mature into chondrocytes. Cartilage is surrounded by fibrous perichondrium capsule which contains undifferentiated progenitor cells
292
What are the three types of cartilage?
Hyaline
Elastic
Fibrocartilage
293
Describe hyaline cartilage and where it is found
GAG rich matrix containing collagen and elastin fibrils
| Found in synovial joints, lone bones and rings of trachea and larynx
294
Describe elastic cartilage and where it is found
Found in the pinna of the ear and the epiglottis - visible on H and E stain but more visible with Van Geisons
295
Describe fibrocartilage
Contains large amounts of collagen and organised into sheets or laminae - found in the annulus fibrosus (intervertebral discs) and pubic symphysis
296
Name three groups of cells with contractile properties
Pericytes - lie alongside small blood vessels
Myofibroblasts - involved in scar formation
Myoepithelial cells - assist in expression of milk during lactation
297
Draw the structure of an artery
See diagrams notes
298
Describe the structure of elastic arteries and give examples
Aorta and pulmonary artery
| Media contains abundant concentric sheets of elastin arranged in circumferential sheets
299
Describe the structure of muscular arteries and give examples
radial and splenic artery
| media comprises of layers of concentric sheets of Smooth muscle 7
300
Define what an arteriole is and describe their structure
Resistance vessel of the circulatory system
Has 3 or fewer muscle layers in media or up to 100um or less in diameter
Lack an external elastic laminae
301
Draw the structure of a capillary
See diagrams sheet
302
What lines capillaries?
Lined by pericytes which form discontinuous layer which becomes continuous as they get larger - where endothelium is incomplete = fenestrate capillaries
303
Draw the structure of a vein
See diagrams sheet
304
Describe the structure of a venule
Wall consists of endothelium surrounded by connective tissue - contractile pericytes wrap around endothelial cells as venules get larger - replaced by smooth muscle as change to veins
305
What are the two parts of the Nervous System?
```
CNS = brain and spinal cord
PNS = Axon processes passing to target organs and tissues
```
306
What type of neurium lies between myelinated axons
Endoneurium
307
What type of neurium surrounds groups of axons to form fascicles
Perineurium
308
What type of neurium binds fascicles together to form nerves
Epineurium
309
Where do motor neurones have their cell bodies
In the grey matter of the spinal cord
310
Where do neurones have their cell bodies
In dorsal root ganglia
311
Where do sympathetic neurones have their cell bodies?
Cell bodies in grey matter of cord and in adjacent sympathetic ganglia
312
Where do parasympathetic neurones have their cell bodies
In the brain and local ganglia
313
Which cell types produce antibodies
Plasma cells and B-lymphocytes
314
Why is glycolysis inhibited by acidosis?
Because PFK-1 is pH dependent and is inhibited by acidotic conditions
315
What stimulates the activity of hexokinase
Stimulated by glucose and insulin
316
What inhibits the activity of hexokinase
Glucose 6 phosphate and glucagon
317
What stimulates the activity of glucokinase
Glucose and insulin
318
What inhibits the activity of glucokinase
Fructose 6 phosphate and glucagon
319
What stimulates the activity of PFK-1
ADP
Fructose 2,6 bisphosphate
Insulin
320
What inhibits the activity of PFK-1
ATP
Citrate
Glucagon
321
Why does fructose 2,6 bisphosphate stimulate PFK-1
Because some fructose 6 phosphate enters the binuclear enzyme complex containing PFK-2 and Fructose 2,6 bisphosphatase. Here the F6P is converted by PFK-2 to F2,6 bisphosphate and is then converted back to F6P by fructose 2,6 bisphosphatase
322
Why does insulin stimulate PFK-1 activity
Because insulin stimulates PFK-2 which increases the conversion of F6P to F2,6bisphophate which is a stimulator of PFK-1 and also inhibits fructose 2,6 bisphosphatase which slows the conversion of fructose 2,6 bisphospho back into fructose 6P
