ILA Flashcards
What is confounding factor
-something related to the outcome (e.g disease) and the characteristic of interest (exposure)
Describe how the information on DNA is used during transcription and translation to construct polypeptides, including the role of messenger RNA (mRNA), transfer RNA (tRNA) and the ribosomes
DNA Replication
- Topoisomerase uncoils he supercoils of DNA
- DNA Helicase breaks the hydrogen bonds between both strands
- Single strand binding protein binds to each strand and prevents them from reannealing
- Primase enzyme uses parent DNA strand to make short RNA primer at the start of he replication fork
- DNA polymerase extends the RNA primer in the 5’ to 3’ direction to create a daughter DNA strand (using free floating nucleotides) - reads the parent strand in the 3’ to 5’ direction
- As replication continues, RNase H enzyme recognises RNA primer within the DNA strand and hydrolyses it
- Ligase enzyme joins the gaps (Okazaki fragments) left by DNA polymerase
Transcription
Transcription factors bind to promoter regions on DNA forming a transcription complex around the TATA box
Topoisomerase uncoils the supercoils of DNA
DNA helicase breaks hydrogen bonds
Single strand binding protein binds to the strands preventing them from reannealing
RNA polymerase through complementary base pairing joins free floating ribonucleotide to parent strand in the 5’ to 3’ direction until it reaches a stop codon
A 5’CAP head and a 3’Poly A tail is added to stop degradation of the pre-mRNA and to allow recognition of the strand by the ribosome
Splicing
Carried out by spliceosomes (small nuclear RNA protein complex)
Remove introns (non-coding) to form a continuous coding sequence of DNA
Allows exon shuffling enabling huge variants of proteins production
Mature mRNA leaves nucleus through nuclear pores
Translation
Mature mRNA binds to ribosomes
3 mRNA bases are read as one codon, the ribosome reads one codon for each aminoacid.
Each amino acid is attached to a tRNA which binds to the anticodon complementary to the codon read by the ribosome.
An enzyme detaches the amino acid from the tRNA
The adjacent amino acids form a peptide bond via a condensation reaction
The codon bases are from 5’ to 3’ in translation
When the ribosome reaches the stop codon, the protein detaches
The mRNA is broken down in the cytoplasm to prevent reproduction
Define a single nucleotide polymorphism (SNP)
A single nucleotide polymorphism is a variation in DNA sequence in which a single nucleotide has changed.
Due to degenerate nature of DNA, SNPs rarely affect functionality or only affect it to a little degree in a person (although sickle cell is an example of it having a big effect)
Affects at least 1% of the population (so fairly common), if less than 1% then it is just a mutation
Describe how a single nucleotide alteration in DNA can result in structural and functional change in its protein product, using haemoglobin S in sickle cell anaemia as an example (consider the changes that may occur in protein primary, secondary, tertiary and quaternary structure)
Missense mutation in the beta chain of adult haemoglobin
17th nucleotide changed from A to T (primary change)
Changed 6th amino acid from glutamic acid (GAG) to valine (GTG) (secondary change) absence of beta pleated sheets
Glutamic acid is charged and polar while valine is nonpolar and hydrophobic so beta chain in haemoglobin folds differently (tertiary) hae group binding site
Causes sickle haemoglobin can polymerise and form sickle shape (quaternary change)
Structural change affecting functionality:
After the oxyhemoglobin delivers oxygen, it becomes a sickle shape
Sickle blood cells do not live as long
The change of shape causes the HbA loses its affinity for oxygen
Low oxygen level can cause occlusion of blood vessels, increased viscosity and increased inflammation
Red cell adhesion to vascular endothelium causes inflammation
Describe how functional change in a protein causes external manifestations of disease
Sickle blood cells do not live as long as destroyed earlier, they only live 10 to 20 days - lower red blood cell count and hemolytic anemia
The change of shape causes the HbA loses its affinity for oxygen - low oxygen delivery to cells so hypoxia and ischaemia of muscle which causes the pain
The sickle cell adhere to the vascular endothelium causing inflammation and clot formation which can lead to blockage and sickle crisis
Sickling crisis - bone pain from reduced blood flow
Kidney, heart and lung damage from reduced blood flow
Chronic anaemia and hyperbilirubinemia - from continued destruction of sickle blood cells
Hyperbilirubinemia presents with symptoms of jaundice (yellow skin and eyes, pale stools, abdominal pain
Describe the distribution of water and sodium in the main fluid compartments.
Total body fluid in 70kg man is 42 L
Intracellular fluid is 28L
Extracellular fluid is 14L - Intravascular fluid is 3L while interstitial fluid is 11L
Intracellular = sodium is 10mmol/L potassium is 110mmol/L Extracellular = sodium is 135mmol/L potassium is 4mmol/L
Define the terms osmolality, oncotic pressure and osmosis. Be able to use these terms to explain the movement of water between the different fluid compartments.
Osmosis is the net movement of water through a semi-permeable membrane from high water potential to low water potential
Osmolality is the number of particles dissolved per Kg of fluid e.g during excess water intake, water moves from the ECF to ICF as ECF osmolality decreases
Oncotic pressure is the pressure exerted by protein pulling water towards themselves e.g albumin
Osmotic pressure is the pressure by which water is drawn into a more concentrated solution through a semi-permeable membrane
Osmotic pressure is pressure exerted by a pure solvent onto a solution to prevent inwards osmosis through a semi-permeable membrane
What are the key routes of water loss from the body? What other routes of excess water loss are there in Mr Palmer’s case?
Key routes of water loss are through urine, faces and insensible loses (sweating and water evaporation from breath)
In Mr Palmers case this would also include vomiting
In a healthy individual what is the normal homeostatic response to;
* Excess fluid (oral or IV) and dehydration. What are the potential dangers of excess water consumption?
- Water moves from the ECF to ICF as ECF osmolality decreases, hypothalamus stops thirst center and secretion of arginine vasopression is inhibited from the posterior pituitary gland
- Hyponatraemia
- Cerebral intracellular overhydration causing confusion, headache and convulsions) - this is water intoxication
- Dehydration
- Water moves from the ICF to ECF as ECF osmolality increases, hypothalamus activates thirst center so person drinks water, hypothalamus produces arginine vasopressin in the supraoptic nucleus and it is secreted by the posterior pituitary gland in the venous outflow which causes the kidneys to retain water
- Hypernatreamia
- Cerebral intracellular dehydration causing headaches, irritability and tremors
Explain water and sodium homeostasis with reference to;
* The hypothalamus and osmoreceptors
The hypothalamus and osmoreceptors
* The vascular organ of lamina terminalis (VOLT) also known as the organum vasculosum of the lamina terminalis (OVLT) and supraoptic crest is one of four circumventricular organs of the brain * The other circumventricular organs of the brain are the subfornical organ, the median eminence and the area postrema * The VOLT capillaries do not have a blood brain barrier so the neurons in the VOLT are osmoreceptors sensitve to high EFC osmolality and osmotic pressure of the blood * Osmoreceptors in the hypothalamus sense change in water potential in the blood passing through the brain, this causes the hypothalamus to produce anti-diuretic hormone which is stored in the posterior pituitary gland and released through venous outflow into the blood * * The subfornical organ also does not have a blood brain barrier and has osmoreceptors sensitive to EFC osmolality and osmotic pressure
