The Patient Semester 2 Flashcards
How are the chromosomes in prokaryotes presented?
All genetic information is stored on one circular chromosome. There is no nucleosome structure. There is only one copy of each gene (haploid).
How are the chromosomes in eukaryotes presented?
Genetic information is split between several linear chromosomes which are built from nucleosomes. They tend to be diploid.
Why do eukaryotic genes tend to be so much larger?
Because they contain introns.
How many chromosomes are present in human DNA?
46, two of each type.
What is the diameter of the nucleus? Where the chromosomes are contained.
6um
What are chromosomes made of?
Chromatin- dark material in the nucleus.
What are the main chromosomal proteins?
Histones- H1, H2A, H2B, H3, H4.
What do chromosomes look like in their non condensed form?
Beads on a string- the beads are the nucleosomes.
How wide is chromatin?
They are 30nm dark fibres.
What is a nucleosome?
It contains 8 peptide chains packed together to form the central core of a chromosome.
What structure does a nucleosome have?
Octameric, two of each histone type.
What is the size of the cylindrical protein core of a nucleosome?
11nm wide
5.5nm deep
Which histone is responsible for nucleosome packing?
H1
What are the letters given to the arms of a chromosome?
Short arm- P
Long arm- Q
What is a chromosome made up of?
Two sister chromatids.
What is the name of the position where chromatids join?
Centromere
How are chromosomes classified?
By the position of the centromere.
What structures are at the ends of chromosomes?
Telomeres
What is a chromosome classified as if the centromere is…
Central?
Off centre?
At the end?
Central- metacentric
Off centre- sub metacentric
At the end- Acrocentric
What is aneuploidy?
Abnormal number of chromosomes i.e. causation of downs syndrome
What is amniocentesis?
Taking a sample of amniotic fluid during pregnancy to test for chromosomal abnormalities.
What are the two stages of eukaryotic cell division?
Nuclear division
Cytokinesis
How many cells are formed when a diploid cell divides by mitosis?
Two new diploid cells
What are the 5 stages of mitotic nuclear division?
Prophase Pro-metaphase Metaphase Anaphase Telophase
What is the part of the cell cycle between divisions?
Interphase
What separates chromosomes during nuclear division?
Kinetochore microtubules
What are the 3 types of microtubules in the spindle apparatus of mitosis?
Kinetochore microtubules- pull chromosomes
Astral microtubules- star formation
Polar microtubules- grow towards centre of the cell
What is the role of a centrosome in the spindle apparatus?
It is the microtubule organising centre.
What occurs at interphase?
Chromosomes and centrosomes replicated
What occurs at prophase?
Chromosomes begin to condense
Sister chromatids become visible
Mitotic spindle starts to form outside the nucleus
Nuclear envelope starts to disappear
What occurs at pro-metaphase?
Nuclear envelope has broken down into small vesicles
Spindle microtubules enter nuclear region
Microtubules attach to kinetochores
What occurs at metaphase?
Chromosomes held in tension at the metaphase plate- half way between poles
Chromosomes attached to kinetochore microtubules
What occurs at anaphase?
Sudden separation of sister kinetochores
Polar microtubules lengthen
Kinetochore microtubules shorten
Chromosomes move to opposite poles
What occurs at telophase?
Nuclear envelope starts to reform
Chromosomes expand and decondense
Cytoplasm restricts
What is the name given to the splitting of the cytoplasm?
Cytokinesis
What are the three types of microtubules?
Astral
Kinetochore
Polar
What does meiosis produce?
4 haploid cells (gametes)
What occurs at meiosis I?
Mitosis phases occur however prophase is elongated to allow for recombination.
How many chromosomes are there in a gamete?
23
What occurs at meiosis II?
Involves the separation of sister chromatids
In meiosis, what occurs at prophase I?
Chromosomes must find their pair, crossing over occurs.
What are chiasmata?
Junctions that form to form crossing over points for recombination in prophase I.
What does bivalent mean?
The chromosomes lining up side by side in prophase I of meiosis.
What are the difference between monozygotic and dizygotic twins?
Monozygotic- from the same zygote
Dizygotic- from two separately fertilised eggs
Where does genetic variability come from in meiosis?
Recombination
Independent assortment
How many rounds of DNA replication and nuclear division occur?
1 round of replication
2 successive nuclear divisions
What is nondisjunction?
Abnormal separation during meiosis II resulting in gametes with the wrong number of chromosomes.
What is Klinefelter Syndrome?
Gives males an extra X chromosome (XXY)
What is Turner Syndrome?
Gives females only one X chromosome.
What is oogenesis?
Female gamete production
What cells are involved in female gamete production?
Precursor cells are known as oogonia and divide to form oocytes.
What are oocytes?
Gametes that have stopped at the early stage of meiosis I and remain dormant in the ovaries until fertilisation protected by a thin layer of somatic cells called the follicle. When menstruation occurs follicles produce mature oocytes. These arrest at meiosis II until fertilisation.
What are spermatogonia?
Stem cells in males in which meiosis occurs.
What are spermatozoa?
Male gametes formed from spermatogonia.
What effect does smoking have on women’s fertility?
Ages a woman’s body clock by 10 years
Reducing chance of conceiving by 10-40%
Define genetics.
The science of genes, heredity and variation in living organisms.
Define heredity.
The passing of traits from parents to offspring.
What is a trait?
A distinct variant of an observed characteristic.
What is a genotype?
Genetic make up that determines the trait.
What is a phenotype?
Physical appearance of an organism’s trait.
What are alleles?
Variations of a gene.
What are homozygous genes?
A pair of identical alleles for a characteristic.
What are heterozygous genes?
Two different alleles for the same characteristic.
What is true/pure breeding?
Whereby particular characteristics always stay the same, throughout generations.
What is pleiotropy?
An allele which has more than one effect on the phenotype- multiple symptoms can be traced back to one defective allele.
What is a dihybrid cross?
Two separate traits in a single cross such as RR YY.
What is polygenic inheritance?
Multiple genes involved in controlling the phenotype of a trait.
What is co-dominance?
A heterozygote shows some aspects of multiple alleles.
What is a locus?
The specific location of a gene or DNA sequence on a chromosome.
What does each part of this represent in terms of a gene locus?
22q12.2
22- chromosome number
Q- Long arm of chromosome (P being short arm)
12.2- position on the sub-arm: region, band, sub-band (bands are numbered from centromere outwards)
What is pharmacogenomics?
Describes the broader application of genomic technologies to drug discovery and development processes.
What is pharmacogenetics?
The study or clinical testing of individual genes and determining genetic variations in a patient (polymorphisms) that give rise to different drug responses.
Give examples of environmental factors that cause variability in drug metabolism and response.
Chemical/drug exposure Cigarettes Alcohol Drug abuse Concomitant medication Age Pathology Adherence
Give examples of genetic factors that cause variability in drug metabolism and response.
Variability in pharmacokinetics (ADME)
Variability in pharmacodynamics (receptors and drug targets)
What is the Human Genome project?
10 year project to sequence the entire human genome- 20,000-25,000 genes.
What is a UTR on a gene?
Untranslated region- non coding.
What is the most common type of genetic polymorphism?
Single nucleotide polymorphism- SNP.
What are the most common SNPs?
Allelic variants
How often do SNPs occur on average?
Every 250-500 base pairs.
Why are exonic SNPs the most important?
They are able to change the amino acid sequence of a protein.
What occurs in individuals with higher than expected rates of metabolism of a drug?
Lack of efficacy
What occurs in individuals with lower than expected rates of metabolism of a drug?
Adverse drug reactions and potential toxicity.
What is signal transduction?
The process whereby information is transmitted to the inside of the cell.
How does signal transduction occur?
Receptor proteins bind signals, conformational changes in the structure of the receptor occur, this converts the chemical signal into one or more intra-cellular signals.
What are the stages of signal transduction?
Signal- Reception- Amplification- Transduction- Response(s)
What are endogenous messenger molecules?
Molecules within a cell that have an internal effect.
Give examples of naturally occurring chemical messenger groups.
Hormones
Neurotransmitters
Local chemical mediators
What is an agonist drug?
A type of drug that binds to and exerts an effect on a receptor (partial or full).
What is an antagonist drug?
A type of drug which binds to a receptor but doesn’t alter the activity of the receptor it simply prevents an agonist from binding/working (competitive or non-competitive).
What are the two main groups of receptor proteins?
Plasma membrane/transmembrane receptors (extracellular)
Cytosolic/nuclear receptors (intracellular)
On average, how many receptor proteins are there in/on cells?
500-100,000 per cell
What sort of molecule is most likely to bind to plasma membrane receptors?
Water soluble/polar molecules
What sort of molecule is most likely to bind to cytosolic receptors?
Lipid soluble/hydrophobic molecules as they can pass through lipid bilayers.
What are the three families of plasma membrane receptors?
Ligand gated ion cells (ion channel function)
G-protein coupled receptors (GTP binding proteins)
Tyrosine kinase receptors (catalytic domain- for phosphorylation)
What are the general structural points of plasma membrane receptors?
Extra-cellular domain for ligand binding
Trans-membrane domain with at least one alpha helices
Intra-cellular domain rich in basic amino acids, can be for catalytic activity
What do GPC receptors contain?
Have a membrane spanning domain consisting of seven trans membrane helices.
How do tyrosine kinase receptors work?
The activated cytosolic region of the receptor can phosphorylate Tyrosine molecules on other proteins.
How do GPC receptors work?
Receptor is activated which in turn activates the G protein. This activates adenylate cyclase which converts ATP to AMP (a cyclic compound).
How are cytosolic receptors characterised?
The have a ligand binding domain and a DNA binding domain.
How do cytosolic receptors work?
Binding to DNA acting as a transcriptional regulator.
What kind of molecules in particular cannot move through the lipid bilayer?
Polar molecules
How do ions move through the lipid bilayer?
Facilitated diffusion down a concentration gradient through water filled ion channels.
Active transport pumps often against concentration gradients.
Approximately how quickly do water filled pores allow ions to pass through?
~ 10^6-10^7 s^-1
How do ligand gated ion channels work?
Binding of the relevant ligand to the receptor part of the ion channel causing it to open or close.
What are Cationic channels?
Allow positive ions through. Generally excitatory and often lead to depolarisation of the cells. E.g. Acetyl choline receptors
What are anionic channels?
Allow negative ions through. Generally exert inhibitory effects once opened- hyperpolarisation.
What are Nicotinic acetyl choline receptors?
Found at neuromuscular junctions, responsible for transporting Na+ and are lined with negative charges.
What is a Gamma-amino butyric acid receptor?
Selectively conducts Cl- ions resulting in hyper polarisation of the neuron.
What are the subunits of an acetyl choline receptor?
5 in total: Alpha (2), beta, gamma and sigma.
What is the width of an acetyl choline receptor?
9nm in diameter total.
2nm diameter in the centre.
What are the two subtypes of nicotinic receptors?
Muscle-type
Neuronal-type
What is tubocurarine?
A plant extract that acts as a poison by inhibiting the nicotinic acetylcholine receptor. Can be used therapeutically as a muscle relaxant.
How do local anaesthetics work?
They block ion channels and prevent the passage of Na+ ions, therefore reducing pain perception.
How do sedatives work?
Increase the ability of GABA receptors to conduct Cl- ions across membranes, driving the membrane potential away from its threshold for activation, reducing communication between neurones.
Give examples of diseases caused by dysfunction of ion channels.
Cystic Fibrosis (genetic) Hypertension Multiple Sclerosis Epilepsy (genetic) Migraine
Give two examples of ligand gated ion channels.
GABA receptor
Acetylcholine receptor
What is a G-protein?
Guanine nucleotide binding protein.
What is an effector system?
Outside trigger causes conformational change in receptor, this sends a message to a molecule which triggers the formation of an intracellular message.
What is the signal transduction process?
Conformational changes in the structure of a receptor protein convert an extra-cellular chemical signal into one or more intracellular signals.
What roles do G protein coupled receptors have?
Mainly physiological- visual sense, smell, behavioural and mood regulation, immune system regulation, autonomic nervous system transmission.
How are GPCRs activated?
Normally activated by hormones or neurotransmitters such as serotonin receptors, muscarinic acetylcholine receptors, adrenergic receptors.
How do beta adrenergic receptors work?
Switched on by adrenaline/noradrenaline
Generally works to relax smooth muscle.
Treatment for things such as asthma generally involves adrenergic agonists.
Treatment for things such as angina generally involves adrenergic antagonists.
What is the basic structure of a Tyrosine Kinase receptor?
Act as receptors and enzymes.
Single extracellular region with N terminal and binding site for chemical messenger.
Single hydrophobic region that traverses the membrane as an alpha helix of 7 turns.
A C terminal chain inside the cell membrane acting as a catalytic binding site.
What happens when the ligand binds to a TK receptor?
In the resting state, the active site is hidden. Upon binding the receptor changes shape revealing the active site on the C terminal chain which now allows phosphorylation to occur on specific tyrosine residues.
How does the EGF tyrosine kinase receptor work?
EGF is a bivalent ligand so can bind to two receptors at the same time resulting in receptor dimerisation and the activation of enzyme activity allowing phosphorylation to occur.
How do insulin receptors work?
Exist as dimers or tetramers so require only the binding of a ligand to activate the TK receptor.
How do growth hormone receptors work?
They are tyrosine kinase linked receptors so do not have catalytic activity but once dimerised they can bind to activate a TK enzyme in the cytoplasm.
How do protein kinase receptors interact with signalling proteins?
Once phosphorylated, the phosphor-tyrosine groups from a TK receptor act as binding sites for signalling proteins.
What are signalling results?
They depend on which proteins bind to kinase receptors. Generally they are the starting point of phosphorylation cascades.
Example: growth factors activating phospholipase C leading to calcium release.
What is the importance of TK receptors in the kidneys?
Some TK receptors catalyse the formation of cGMP from GTP. They act as both receptor and enzyme (guanylate cyclase).
cGMP opens sodium channels in the kidneys so the excretion of Na+ is promoted.
Give examples of diseases connected to protein kinases.
Cancer, rheumatoid arthritis, asthma, psoriasis.
How can protein kinases be used as drug targets?
Inhibition of phosphorylation activity by blocking ATP binding.
Disruption of protein-protein interactions.
Down-regulation of kinase gene expression.
What are the main features of intracellular receptors?
Not membrane bound, found within cells.
Important in directly regulating gene expression.
Also known as nuclear hormone receptors.
What is the basic structure of intracellular receptors?
Single protein containing a ligand binding site at the C terminal.
Binding region for DNA near the centre with 9 cysteine residues, 8 of which bind zinc ions for stabilising the DNA binding region.
What do intracellular receptors affect?
Homeostasis, embryonic and sexual development, reproductive function, metabolism, bone and muscle maintenance.
How do intracellular receptors work?
A ligand binds to the reduced by the induced fit model, this leads to dimerisation. The dimer binds to a co-activator protein and then the entire complex binds to a specific region of the cells DNA. Two receptors and two binding regions mean that the complex recognises two identical sequences of nucleotides.
Give examples of specific intracellular receptors.
Glucocorticoid
Oestrogen
Progesterone
What are the two major families of transporters in humans?
ATP binding cassettes
Solute carriers
Where are the membrane transporters most relevant in drug development?
Epithelia of the intestine, liver and kidney
Endothelium of the blood-brain barrier
What are the roles of transporters in the liver?
Uptake of drugs from blood into hepatocyte
Excretion of drugs into the bile (efflux)
What are the Organic Anion Transporting Polypeptides?
11 different OATPs
Mediate uptake of substrates in electro-neutral manner- dependent on Na+ and ATP
E.g. OATP1B1- 12 putative transmembrane domains and large extracellular loop
Where are OATPs found?
B1 expressed throughout the liver
B3 mainly in the perivenous areas of the liver
What drug is OATP1B1 mainly responsible for?
Involved in active uptake of statins
How do statins work?
Inhibit HMG-CoA reductase, reducing cholesterol synthesis in the liver.
Give an example of therapeutic consequences of polymorphisms of OATP1B1.
Inter-individual variability in pharmacokinetics of certain drugs
Increased risk of adverse effects (myopathy in statins)
What is rhabdomyolysis?
The breakdown of damaged skeletal muscle, causing the release of myoglobin into the bloodstream. If you have too much myoglobin in your blood, it can cause kidney damage.
Give examples of drugs that inhibit OATP1B1.
Ritonavir
Cyclosporin
What is the consequence of OATP1B1 inhibition?
Increased plasma concentrations of the drug, increased risk of adverse effects.
What do uptake transporters do?
Transport substrates into cells
What do efflux transporters do?
Pump substrates out of cells
What are ABC transporters?
ATP Binding Casettes
What mechanism do efflux transporters use?
Primary active transport using ATP as an energy source
What is P-glycoprotein?
An efflux transporter
A multidrug resistance transporter- MDR1
12 membrane spanning helices
2 nucleotide binding domains (NBDs, bind and hydrolyse ATP)
What is BCRP?
Breast cancer resistant protein, transports methotrexate
What are MRPs?
Multidrug resistance associated proteins, efflux transporters
What are the features of MRP1?
MRP1 – 17 membrane spanning helices and 2 NBDs
What are efflux transporters used for?
Protecting the body from exposure to dietary and environmental xenobiotics e.g. benzo[a]pyrene
Metabolise xenobiotics and then the metabolites excreted.
How can efflux transporters effect drugs?
Absorption
Distribution in tissues/organisms
Metabolism
Excretion
Give examples of P-glycoprotein substrates.
Doxorubicin Daunorubicin Amprenavir Indinavir Atrovastatin Erythromycin
Give examples of BCRP substrates.
EE-O-sulphate
Benzo[a]pyrene-3-sulphate
Where are P-gp and BCRP expressed?
Apical membrane of the intestinal epithelial cells.
What is the main substrate for MRP2 and MRP3?
EE-O-glucoronide (Ethinylestradiol-contraceptive pill)
Give examples of drugs that P-gp reduces the absorption of.
Digoxin
Cyclosporin
What are the two major excretion routes for drugs?
Liver -> bile -> intestine
Kidney -> urine
How does excretion of drugs via the liver occur?
P-gp expressed on hepatocyte canicular membrane
Drugs are pumped into the bile
How does excretion of drugs via the kidney occur?
P-gp expressed in kidney cell membranes, pumped out into the tubular fluid then into the membrane.
What is the Blood-Brain barrier formed by?
Brain capillaries
How to P-gp and BCRPs work in the brain capillaries?
Protect the brain from toxins, however they only allow daily small drug concentrations into the CNS making drug delivery more difficult.
How do efflux transporters work in the placenta?
Protect the developing foetus from drugs and xenobiotics that they are susceptible too.
Example- thalidomide as a teratogen
How do efflux transporters affect cancer cells?
P-gp, BCRP, MRPs expressed in some cancers, pump chemotherapeutic drugs out of malignant cancer cells. Reduces intracellular drug accumulation allowing cells to survive and proliferate.
What are MDRs?
Multi drug resistant cells, do not respond to chemotherapy making them more likely to be fatal
What is pharmacokinetics?
What the body does to the drug.
What is pharmacodynamics?
What the drug does to the body.
What is ADME?
Absorption- GI tract
Distribution- circulation
Metabolism- liver
Excretion- kidneys
What are the three main functions of the GI system?
Digestion of food
Absorption of nutrients (and drugs)
Elimination
What are the 4 regions of the GI tract?
Mouth
Oesophagus
Stomach
Small Intestine
What are the 4 accessory organs of the GI tract?
Salivary glands
Liver
Gall bladder
Pancreas
What occurs in the mouth during digestion?
Breaks up food particles
What occurs in the oesophagus during digestion?
Transport of food to the stomach via sphincter
What occurs in the stomach during digestion?
Secretion of gastric juices for chemical digestion, mixing of food and gastric juices, mechanical break down of food
What is peristalsis?
A series of wave-like muscle contractions that moves food to different processing stations in the digestive tract beginning at the oesophagus.
What role does the stomach play in absorption?
Release of gastric juices (HCl) is controlled by the vagus nerve and the hormone gastrin.
Digestion of proteins (pepsin) is initiated.
What is the role of the mucus coating of the stomach?
Lubricates and protects the epithelial surface against pepsin.
What is chyme?
The acidic fluid which passes from the stomach to the small intestine, consisting of gastric juices and partly digested food.
What affects gastric emptying?
Volume of meal Kcal content Fat content Protein content Liquid/solid state
What are the three regions of the small intestine?
Duodenum
Jejenum
Ileum
What occurs in the small intestine?
Completes digestion of nutrients in chyme
Major site of absorption of nutrients and orally administered drugs
Site of 1st pass metabolism
Movement of food residues to large intestine
How is the small intestine adapted for absorption?
Large surface area
High perfusion
Exposure to enzymes and solubilisers
Receives secretion from liver and pancreas
What makes the surface area of the small intestine so large?
Mucosa- epithelium and connective tissue with blood and lymphatic vessels.
Villi- extend from the luminal surface of the small intestine
Microvilli brush border
Why is the large surface area of the small intestine so relevant in drug absorption?
Dissolved drugs are absorbed across the gut wall by passive diffusion usually- can be paracellular or transport-facilitated.
Enterocytes contain metabolic enzymes for 1st pass metabolism.
Blood perfusing intestine goes into liver via hepatic portal vein then not systemic circulation.
What is coeliac disease?
A chronic autoimmune disorder of the small intestine where inflammation is triggered by consumption of gluten. It causes atrophy of villi in the small intestine.
What occurs in carbohydrate digestion?
Starch is broken down by amylase into disaccharides.
Disaccharides are broken down by enzymes in the small intestine into monosaccharides which is transported across the membrane into the blood.
What occurs in protein digestion?
Peptides are broken down in the stomach by pepsin, the fragments are then broken down in the small intestine by trypsin and chymotrypsin from the pancreas into amino acids which are transported to epithelial cells by active transport.
What occurs in lipid digestion?
Emulsification by bile salts to form small lipid droplets followed by formation of fatty acids by pancreatic lipase. Transport occurs by micelle formation.
What occurs in the large intestine during digestion?
Reabsorption of water and salts from chyme.
Mixing and propulsion of contents.
Indigestible residue and liquid eliminated as faecal waste.
What is the relevance of bacteria present in the distal intestine?
Contribute to normal digestion.
Ferment carbohydrates and proteins escaping digestion.
Able to metabolise some drugs and xenobiotics.
What is the gut-brain axis?
The biochemical signaling that takes place between the gastrointestinal tract and the central nervous system.
Define intravascular.
Placement of drug directly into the blood.
Give examples of extravascular routes of administration.
Oral, sublingual, subcutaneous, rectal, intramuscular etc.
How is absolute bioavailability usually measured?
Usually assessed with reference to an intravenous dose.
What is relative bioavailability?
Comparison of bioavailability between formulations of a drug given either by the same or different routes of administration.
What is BCS?
Biopharmaceutics classification system.
Class I- most soluble and permeable drugs
Class II- permeable but low solubility
Class III- soluble but low permeability
Class IV- low solubility and permeability
What is gastric emptying?
Controls the delivery of drug (and food) to small intestine
What is the difference between fasted and fed gastric emptying?
Gastric emptying occurs more quickly when fasted, therefore drug delivery to the upper small intestine is rapid.
How can gastric emptying benefit poorly soluble drugs?
Poorly soluble drugs should be taken with food- delayed gastric emptying so increased absorption.
What are the effects of gastric bypass surgery on drug absorption?
Reduction in surface area of stomach, alterations in pH, bypass of main areas of drug absorption (duodenum and jejunum).
What are the roles of the circulatory system?
Allow cells to exchange substances with each other and the environment
Regulation of blood flow and blood pressure
Produces immune cells
Distribution of drugs around the body
What are the four determinants of blood pressure?
Blood volume- higher volume puts more strain on system
Overall compliance- expansion/retraction of vessels
Cardiac output- increase in output gives higher arterial blood pressure
Peripheral resistance- higher resistance, higher arterial blood pressure
What are the features of arteries?
Carry oxygenated blood from the heart to the organs
Thick pulsating muscular wall
Branch into arterioles and capillaries
What are the features of veins?
Carry deoxygenated blood back to the heart
Capillaries join and widen into venules
Lower pressure, thinner muscle layer compared to arteries
Valves prevent backward flow of blood
How does distribution of blood flow vary?
Highly perfused- lungs, kidneys, liver, brain
Poorly perfused- adipose, skin
What is vasoconstriction?
Vessel diameter reduces, more blood available for other sites
What is vasodilation?
Vessel diameter increases, decrease in vascular resistance and blood pressure
What are the main roles of the Renin-angiotensin-aldosterone system?
Response to threats that compromise blood pressure stability, such as hypotension, blood loss and excessive loss of sodium and water.
What is cardiac output?
Volume of blood pumped by the heart- around 5-6L/min
What is the function of the right heart?
Collects deoxygenated blood from the body and pumps it to the lungs.
What is the function of the left heart?
Collects oxygenated blood from the lungs and pumps it to the rest of the body.
What are the 6 steps of heart function?
1- Collection of venous blood
2- Moves from right atrium to right ventricle
3- Exits right ventricle through pulmonary valve, into pulmonary artery
4- Blood rich in O2 and low in
CO2 leaves lung via
pulmonary vein to left atrium
5- Enters left ventricle via mitral valve
6- Pumped out of left ventricle
to main aorta and systemic
circulation
What occurs at atrial systole?
Atrial blood pressure , forces blood into the ventricles.
What occurs at ventricular systole?
Ventricular blood pressure, forces blood out of the ventricles into arteries.
What occurs at cardiac diastole?
Relaxation of ventricles and atria, refilling of blood
What occurs at ventricular diastole?
Valves open when pressure in the ventricles is lower compared to atrium.
What is atrial fibrillation?
Abnormal electrical impulses giving irregular pulse- the most common type of arrhythmia.
What are the treatment options for Atrial Fibrillation?
Reduce risk of stroke- warfarin
Control AF heart rate- beta-blockers, digoxin
Cardioversion- electric shock
Catheter ablation- destroying abnormal tissue
Pacemaker
What are the roles of the blood?
Transport of oxygen, nutrients, hormones Removal of waste such as carbon dioxide, lactic acid, urea pH and temperature regulation Defence- immune cells Coagulation
What are the main components of the blood?
Plasma- 55% of volume
White blood cells- <1% of volume
Platelets- 1:10 or 1:20 ratio with red blood cells
Red blood cells- 40-45% of volume
What are the features of blood plasma?
Straw-yellow colour
Dissolves substances
Contains proteins- mainly albumin
Transport medium
What are the three types of white blood cells?
Neutrophils- phagocytosis, destruction of bacteria
Monocytes/macrophages- phagocytosis
Lymphocytes- immune response
What are the features of white blood cells?
Produced in the bone marrow
Life span of around 5 days
Neutrophils make up 50-70% of all white blood cells
What is neutropenia?
Low neutrophil count, common side effect of many chemotherapeutic drugs
What are the features of platelets?
Important for clotting
No nucleus
What is thrombocytopenia?
Low platelet count, leads to excessive bleeding
What is thrombocytosis?
High platelet count, leads to increased formation of clots and risk of stroke/myocardial infarction
What are the features of red blood cells?
Represents 1/3 of total cell count in the body
Maintenance of blood flow
Transport of oxygen and carbon dioxide
What is the lymphatic system?
Network of lymph nodes, ducts and vessels returning excess fluid to the blood circulation under low pressure.
What roles does the lymphatic system have?
Produces immune cells
Lymph nodes/glands- filter lymph for bacterial infection
Role in absorption of monoclonal antibodies
What is the normal blood pressure value?
120/80 mmHg
What is drug distribution?
Reversible transfer of the drug between the blood and other tissues within the body.
What does drug distribution depend on?
Perfusion of each organ Permeability of tissue membranes Physiochemical properties of the drug Binding of the drug to plasma and tissue components Partitioning of the drug
What is first pass metabolism?
Loss of a drug as it passes through the intestine and liver during absorption.
What are the main functions of the liver?
Secretion of bile
Synthesis and storage of many nutrients (e.g. vitamins and lipids)
Breakdown of old red blood cells
Synthesis of plasma proteins (e.g. albumin)
What metabolic elimination occurs in the liver?
Nitrogenous waste
Alcohol
Xenobiotics (e.g. drugs, additives, pollutants)
What controls the blood supply of the liver?
Portal vein- 1.1L/min bringing venous blood from the GI tract
Hepatic artery- 0.4L/min carrying oxygenated blood
Highly perfused organ
What are the hepatic sinusoids?
On entry to the liver, blood drains into hepatic sinusoids which are lined up by fenestrated epithelium.
What are hepatocytes?
Major liver cells- representing 70-80% of the liver mass.
What is the space of Disse?
Separates the hepatocytes and sinusoids.
What are Kupffer cells?
Specialised macrophages found in the liver.
Describe the processes of metabolism in the body.
Main mechanism of drug elimination with the liver and intestine being major sites.
Metabolites are more polar and hydrophilic than the parent drug and really excreted.
Describe the processes of excretion in the body.
Renal excretion- via the kidneys
Hepatic excretion- billiard excretion of drugs
What is drug clearance?
CL= the volume that is cleared of a drug per unit time e.g. L/h
What is the role of the liver in metabolism and elimination of drugs?
Hepatocytes contain a large number of metabolic enzymes e.g. cytochrome P450 and glucuronidation enzymes
What is the CYP3A4 enzyme?
Found in the liver and metabolises over 50% of drugs currently available
What are the key features of metabolic elimination?
A dominant elimination route for many therapeutic drugs.
Inhibition of metabolic enzymes is the most common form of drug-drug interaction.
What are the roles of transporters in the liver?
Mediate uptake of drugs into the hepatocyte e.g. atorvastatin uptake via OATP1B1
Excretion of drugs into the bile via efflux transporters e.g. excretion of rosuvastatin by BCRP
What is enterohepatic recirculation?
The circulation of biliary acids, bilirubin, drugs, or other substances from the liver to the bile, followed by entry into the small intestine, absorption by the enterocyte and transport back to the liver.
What is liver cirrhosis?
Commonly caused by excessive alcohol intake, Hepatitis B and C
Decreased liver volume and blood flow
Altered liver function, reduced activity of some metabolic enzymes and reduced albumin synthesis
Renal function generally impaired
Rarely reversible
What are the main structures in the urinary system?
2 kidneys
2 ureters
Urinary bladder
Urethra
What roles do the kidneys have?
Elimination of nitrogen containing metabolic waste
Maintaining water, ionic and pH balance in body fluids
Central role in filtering blood and forming urine
Production of hormones
Elimination of drugs and metabolites
What is urea?
Formed during the breakdown of amino acids
What is uric acid?
Formed during the breakdown of nucleic acids
What is a nephron?
The functional unit of the kidney
What is the renal corpuscle?
Consists of Bowman’s capsule (spherical structure) and Glomerulus (cluster of capillaries)
Filters the blood
Remaining blood leaves the glomerulus via efferent arteriole
2 arterioles in series with capillaries
What is GFR?
Glomerular filtration rate measures kidney function.
How is the GFR determined?
Using insulin or creatinine not bound to plasma proteins and not secreted or reabsorbed.
What are the standard values for GFR?
20 yr old male- 120ml/min
20 yr old female- 110 ml/min
Decreases by 1% yearly from 20
How does glomerular filtration work?
Filtration from glomerular capillaries to the Bowman’s capsule
Non-selective, passive process
Filters: water, urea, uric acid, Na, K, Cl, small molecules, drug molecules unbound to plasma proteins
What is tubular secretion?
Selective transport from the peritubular fluid to the lumen of renal tubules for excretion.
Occurs in proximal and distal tubes via numerous transporter proteins
H, K and NH4 actively secreted to maintain blood pH
What transporters are present in the basolateral membrane of renal epithelia?
Organic anion transporter- OAT1
Organic cation transporter- OCT2
What is the role of OAT1?
Transport of small organic anionic molecules
Elimination of aciclovir, zidovudine, methrotraxate
What is the role of OCT2?
Transport of small organic cations
Excretion of metformin, amaliplatin and pindolol
What is tubular reabsorption?
Selective transport of molecules from the lumen of the renal tubules back to the plasma.
Involves either transporters of passive diffusion.
Which molecules are reabsorbed in tubular reabsorption?
Na, nutrients (sugars, amino acids)
85% water, countercurrent mechanism to maintain osmolarity
Lipophillic, unionised drugs.
How is the loop Henle involved in tubular reabsorption?
Descending loop of Henle is not permeable to Na
Ascending loop of Henle is not permeable to water, active reabsorption of Na
What affects the passive reabsorption of drugs?
Drug lipophilicity and degree of ionisation.
Unionised from must be lipophilic enough to pass back through the membrane
What is the average urine flow?
1-2ml/minute at a pH of 5-7.8
Describe the efficiency of nephron units.
Remove waste but conserve basic requirements such as water, glucose and mineral ions.
180L filtered per day with only 1.5L of urine lost
How does diabetes mellitus affect nephron units and urination?
Glucose in urine, osmotic pressure in renal tubule, reduced water reabsorption and increase urination.
In what cases of renal impairment should dose adjustment occur?
Fraction of drug excreted via the kidneys is >50%
Drugs with narrow therapeutic index
Impaired metabolism
What is a pharmacokinetic drug-drug interaction?
An interaction affecting absorption, protein binding, transporters, renal secretion or most commonly metabolism.
What is a pharmacodynamic drug-drug interaction?
An interaction acting on the pharmacological effect of the drug.
What percentage of hospital admissions are due to drug-drug interactions?
7%
In what cases are the risks of drug-drug interactions increased?
Narrow therapeutic index Renal/hepatic impairment Elderly Anticoagulants Antihypertensives Antidiabetics
What is a therapeutic index/window?
The window in which the pharmacological effect is at its highest without the toxicological effect being noticeable.
What are the main form of metabolic drug-drug interactions?
Inhibiton interactions- whereby co-administration of the inhibitor leads to increased plasma concentrations of the ‘victim’ drug as it is not metabolised.
What is internal/cell respiration?
Metabolic processes at which cells breakdown carbohydrates, amino acids and fats to produce ATP energy.
What is the role of mitochondria in respiration?
Production of energy through oxidative phosphorylation requires energy source and oxygen. By products include water and carbon dioxide.
What is external respiration?
Exchange of gases between body and environment- inhalation and exhalation cycle
What is the role of external respiration?
Inhalation provides oxygen
Exhalation eliminates carbon dioxide
Blood transports oxygen and carbon dioxide between lungs and tissues
Exchange of oxygen and carbon dioxide between blood and tissues by diffusion.
What is the process of inhalation?
Contraction of the diaphragm, expansion of intrapleural space and increase in negative pressure to draw air in.
What is the process of exhalation?
Relaxation of the diaphragm, decrease in volume of intrapleural space and increase in positive pressure to force air out.
What organs are involved in the respiratory system?
Lungs- inside pleural sac in ribcage
Diaphragm- muscle responsible for inhalation and exhalation
What is the role of the conducting airways?
Allow air to enter/exit
Filterm warm and humidify inhaled air
Epithelium composed of several cell types
What particular feature does the trachea have?
Cartilage rings on the outside protect it and keep it open.
What are the features of bronchi?
Branches to form bronchioles
Produce mucus to trap dirt particles and microorganisms (goblet cells)
Continuously cleared by cilia to pharynx and then swallowed
How do the cilia in smokers differ?
They are non-functional.
What is pulmonary circulation?
Pulmonary artery and vein
What is bronchial circulation?
Provides oxygenated blood to larger airways
What are the features of alveoli?
~500 million with a total surface area of 70m^2
Radius of 0.1nm and thickness of 0.2µm
Primary site of gaseous exchange and passive diffusion
What is the respiratory membrane?
Alveolar wall- single layer of epithelium cells
Capillary wall- single layer of endothelial cells
What concentrations of oxygen and carbon dioxide are present in the air?
Oxygen- 20%
Carbon dioxide- <1%
What are erythrocytes?
Red blood cells containing haemoglobin and carbonic anhydrase.
What are the features of haemoglobin?
Iron containing protein involved in oxygen transport
Each subunit is globular with an embedded haem
Oxyhaemoglobin- red
Deoxyhaemoglobin- blue
What is the role of carbonic anhydrase?
Fast enzyme known, important for eliminating carbon dioxide.
Mostly transported dissolved in plasma as HCO3-
What are the eight stages in gas exchange?
1- inhalation
2- diffusion of oxygen into capillary
3- binding of oxygen to haemoglobin
4- oxygen leave haemoglobin and diffuses into tissue
5- carbon dioxide diffuses into capillaries and is converted to HCO3-
6- Travels to the lungs and is converted back to carbon dioxide
7- diffusion of carbon dioxide into alveoli
8- exhalation
What are the features of alveolar macrophages?
Derived from circulating blood monocytes 12-14 AMs in the body Phagocytic cells- defence again pathogens and inhaled drugs Secretion of cytokines0 interleukin 1a Efficiency reduced in COPD and smoking
How do lysosomes trap drugs in AMs?
Basic drugs and macrocodes accumulate in AMs and become trapped in acidic lysosomes due to reduced ability of the protonated form to diffuse back into the cytosol.
What is phospholipidosis in the lungs?
Excess accumulation of phospholipids, can be due to continuous drug accumulation and lead to foamy alveolar macrophages.
What is asthma?
Chronic inflammation of airways causing contractibility of smooth muscles, reversible narrowing of airways.
What can cause asthma?
Family history Eczema and allergy Broncholitis Premature birth Secondhand smoking Exposure to substances Hormones
What long term treatment options are available for asthma?
Inhaled corticosteroids (anti-inflammatory) e.g. beclomethasone, fluticasone Leukotriene modifiers (relieve symptoms for 24h) e.g. montelukast Long acting beta agonists (open airways) e.g. salmeterol, formeterol
What quick relief medications can be used for asthma?
Short acting beta agonists e.g. albuterol
Bronchodilators e.g. ipratropium
Corticosteroids
What is COPD?
One or more of the following conditions mainly caused by smoking.
Inflamed airways, damaged alveoli, narrowing of airways, difficulty breathing
What is emphysema?
Breakdown of alveolar membranes reducing surface area often found in COPD sufferers.
What is chronic bronchitis?
Inflammation of the bronchi and excess mucus production causing narrowing of the airways, often found in COPD sufferers.
What treatment can help COPD?
Stop smoking, eating well to prevent weight loss and infections, exercise. Pulmonary rehabilitation Oxygen therapy Breathing machine Bronchodilator or steroid inhalers
What are the benefits of direct drug delivery into the lungs?
Rapid access to systemic circulation
Avoids first pass metabolism- site of action
What does the multicellular state lead to?
Specialisation and division of labour- giving rise to specific tissues and organs
What is the unique feature of vertebrates?
They have several systems to coordinate and regulate activities of cells
What occurs is there is a breakdown in cell communications?
Malfunction
Disease
What are the three methods of animal cell communication?
Secretion
Contact
Inter-cellular
What is secretion?
Remote communication by secreting chemical messengers
What is contact cell communication?
Communication by membrane bound molecules such as a processed antigen
What is inter-cellular communication?
Communication via gap junctions
What is the easiest method to send a message a long distance in the body?
Via the bloodstream
What is responsible for long distance chemical signalling?
The endocrine system and hormone secretion e.g. an infection on the toe
What is responsible for medium distance chemical signalling?
Paracine cells which secrete local chemical mediators e.g. a cut on the knee
What is responsible for short distance chemical signalling?
Synaptic signalling- involving the production of neurotransmitters. Although the electrical messages may travel a long distance in this case, the chemical signals travel only across the synapse
What do endocrine cells do?
Secrete hormones into the bloodstream e.g. thyroid
What do exocrine cells do?
Secrete non hormonal substances into ducts e.g. bile duct in the liver
What do paracrine cells do?
Release local chemical mediators to neighbouring cells
What are neuroendocrine cells?
Dual function nerve cells with endocrine functions e.g. hypothalamus
What do neurotransmitters do?
Pass chemical across the synapse to trigger electrical impulse e.g. acetyl choline
What are neurocrine cells?
Nerve cells with paracrine function
Give examples of hormones from different areas of the body?
Insulin in the pancreas
Adrenaline in the adrenal glands
Endorphines in the brain
What are primary endocrine organs?
Organs whose primary function is the secretion of hormones
What are secondary endocrine organs?
Organs with a non endocrine primary function
What is the pineal gland?
Controls circadian rhythm and produces melatonin
What is the hypothalamus?
Regulation of body functions, produces stimulatory and inhibitory hormones
What is the pituitary gland?
Produces hormones that tend to regulate other primary glands and controlled by the hypothalamus
What is the thyroid gland?
Produces thyroxine which is very important in metabolic regulation
What are the parathyroid glands?
Four small glands attached to the back of the thyroid gland
What is the thymus gland?
Important in neonates for the development of the immune system
What is the adrenal gland?
Triangular shaped glands on top of the kidneys that produce adrenaline.
How is the pancreas involved in the endocrine system?
Regulates blood glucose levels and produces insulin
How are the testis involved in the endocrine system?
Important for producing testosterone in males
How are the ovaries involved in the endocrine system?
Produce oestrogen and progesterone in females
What sort of chemicals are hormones?
Modified amino acids e.g. adrenaline
Small peptides/proteins e.g. insulin
Steroids e.g. sex hormones
What sort of chemicals are local chemical mediators?
Amino acid derivatives e.g. histamine
Fatty acid derivatives e.g. prostaglandins
Small proteins e.g. EGF
Dissolved gases e.g. nitric oxide
What sort of chemicals are neurotransmitters?
Amino acids
Amino acid derivatives e.g. GABA, serotonin
Choline derivatives e.g. acetyl choline
Small peptides e.g. enkephalins
What is the process of forming adrenaline?
Catecholamine metabolism- tyrosine forms L-dopa which forms dopamine which forms noradrenaline and finally adrenaline
What happens to cells if they are left alone?
They need chemical signals from other cells just to survive let alone divide, differentiate or carry out apoptosis
How can cells respond to chemical signals?
Organism level processes such as growth, development, tissue maintenance etc
Different cells react in different ways to the same signal
Tremendous variability in signal transduction mechanisms
How do the speeds of cellular responses vary?
Neurotransmitters act rapidly (~1ms) due to electrical impulses and local concentrations tend to be high
Hormones act at low concentrations but have lasting and widespread effects
What are the three different nervous systems within the body?
Central nervous system
Peripheral nervous system
Enteric nervous system
What is the role of the CNS?
Receives and process information
Coordinations organ function
What does the CNS consist of?
Brain
Spinal cord
What is the frontal lobe of the brain responsible for?
Reasoning Planning Speech Movement Emotions Problem solving
What is the parietal lobe responsible for?
Movement
Orientation
Recognition
Perception of stimuli
What is the occipital lobe responsible for?
Visual processing
What are the temporal lobes responsible for?
Perception/recognition of auditory stimuli
Memory
Speech
What does the peripheral nervous system do?
Sends sensory input and visceral information to the CNS
What does afferent mean?
In to
What does efferent mean?
Out of
How long does it take for a human to react to a stimulus?
At least 100 milliseconds
Give an example of an autonomic response
Vasodilation and sweating in response to increased body temperature
Give an example of a somatic response
Putting your foot on the break in response to seeing a red light
How do the somatic and autonomic nervous systems differ?
Autonomic is NOT under voluntary control
What is the longest neurone in the human body?
Runs from the lower back to the big toe.
What is the soma?
The cell body of a neurone
What is a synapse?
The gap between neurones
What is the axon terminal?
The end of the presynaptic neurone
What are dendrites?
The part of a neurone that sticks out and receives input from other neurones via synapses
What is an action potential?
The electrical impulses transmitted by neurones
What happens if there is a mutation in the SCN9A gene?
A mutation in the sodium channel gives a congenital insensitivity to pain
How does an action potential arise?
Movement of sodium and potassium ions down an electrochemical gradient via an ATPase enzyme, making the outside of the cell more positive
What is the resting potential of a neurone?
-70mV
How does an ATPase molecule alter the charge of the neurone?
Each cycle removes 3 sodium ions and transfers 2 potassium ions into the cell, making the membrane polarised.
What happens to the action potential in the presence of a stimulus?
Causes sodium channels to open, the ions rush into the cell down an electrochemical gradient, depolarising the membrane
What occurs after an action potential has been formed?
Sodium channels close so they can no longer enter, potassium channels open allowing the ions to exit down an electrochemical gradient, repolarising the membrane.
How does an action potential travel along a neurone?
Potassium channels close so potassium ions cannot exit. Adjacent sodium channels open allowing ions to enter. The same process repeats down the neurone, moving the action potential along
What happens when the action potential reaches a synapse?
Calcium channels open allowing ions to enter the cell, releasing a neurotransmitter into the synaptic cleft which binds to the adjacent neurone.
What are the three important amine neurotransmitters?
Serotonin
Dopamine
Acetylcholine
What is serotonin?
Neurotransmitter that influences mood
What is dopamine?
Neurotransmitter that is involved in coordinating movement, produced in the substantia nigra
What is acetylcholine?
Neurotransmitter found in neuromuscular junctions and broken down by acetylcholinesterase
What does the botulinum toxin do?
Blocks acetylcholine release, is the most toxic substance on earth but used in botox.
What is glutamate used for as a neurotransmitter?
Excitory neurotransmitter as it produces an action potential
What is glycine used for as a neurotransmitter?
Inhibitory neurotransmitter as it prevents an action potential
GABA is another example
What is thiopental?
Dampens down the nervous system- leading to death, used on death row
Why is drug delivery to the CNS problematic?
The blood brain barrier is highly restrictive in order to protect the brain
How prevalent are CNS diseases?
1 in 4 will suffer from a CNS disease at some point
How prevalent are strokes?
1 in 5 women
1 in 6 men
will have a stroke by the age of 75
What is an ischemic stroke?
Most common type of stroke, blood vessel occluded (e.g. clot or plaque fragment travels to the brain and the lack of oxygen and nutrients causes cell death
How can strokes be treated?
Tissue type plasminogen activators (Alteplase) should be administered as soon as possible and within 4.5 hours of symptom onset.
What is a haemorrhage stroke?
Less common but more likely to be fatal. Bleed onto the brain.
What are the risk factors of haemorrhage stroke?
High bp, smoking, obesity, poor diet, lack of exercise, diabetes
What is Parkinson’s?
Causes death of dopaminergic neurones leading to lack of control in movement
How is Parkinson’s treated?
Replenish dopamine levels with medication such Levodopa
What is Alzheimer’s?
Disease leads to physical reduction in brain size and activity. Insoluble form of amyloid-beta monomers aggregate to form oligomers which are highly toxic to neurons.
How is Alzheimer’s treated?
Only symptoms can be treated by the use of acetylcholinesterase inhibitors such as donepezil and rivastigmine.
How do selective serotonin re-uptake inhibitors work?
Prevent reuptake of serotonin into the pre synaptic neuron
Serotonin remains in the synapse longer and is therefore more likely to have an effect
What proportion of cancers affect the CNS?
Around 20%
What are athrocytes?
Star shaped cells that hold everything together in the CNS.
How can astrocytoma be treated?
Radiotherapy to slow down growth
Surgery and carmustine implants (wafers that are packed full of anticancer agent)
Surgery and temozolimide (chemotherapy)
What are oligodendrocytes?
Cells that produce the myelin that covers neurones
How is oligodendroglioma?
If fast growing (high grade)- surgery followed by radio therapy
Possibly chemotherapy- procarbazine, lomustine, vincristine
What are ependymal cells?
Produce fluid within the CNS
What is the internal milieu?
The extra cellular fluid environment
How is the stability of the internal milieu maintained?
The endocrine system maintains homeostasis by secreting hormones.
What are the three types of hormone that influence the reproductive system?
Peptides/proteins e.g. FSH, LH
Steroids e.g. oestrogen, progesterone, testosterone
Fatty acid derivatives e.g. eicosanoids
What are gonadotrophins?
Chemical complex peptide hormones involved in reproductive cycles that exert their effects by GPCRs.
What are the features of steroid hormones?
Derived from cholesterol and differ only in the ring structure and side chains attached, all lipid soluble
What are the main roles of oestrogen?
Brain- maintain body temp, delay memory loss, regulate parts of the brain that prepare the body for reproductive development.
Heart/liver- regulate cholesterol production
Breasts- stimulates development and prepares glands for milk production
Uterus- stimulates maturation, prepares to nourish developing foetus
Ovaries- stimulates maturation, stimulates the start of the menstrual cycle
Vagina- stimulates maturation, maintain lubricated and thick lining
Bone- preserves bone density
What are the main roles of testosterone?
Skin- hair growth, balding, sebum production
Brain- libido, aggression
Muscle- increase in strength and volume
Liver- synthesis of serum proteins
Kidney- stimulation of erythropoietin production
Bone marrow- stimulation of stem cells
Sexual organs- penile growth, spermatogenesis, prostate growth and function
Bone- accelerated linear growth closure of epiphyses
What are eicosanoids?
Derived from polyunsaturated fatty acids. Including prostaglandins, thromboxanes, leukotrienes
Why is pulsatile hormone release important?
If GnRH is given once hourly, gonadotropin secretion and gonadal function are maintained normally. A slower frequency won’t maintain gonad function. Faster or continuous infusion inhibits gonadotropin secretion and blocks gonadal steroid production
What evidence of feedback control is there in reproductive organs?
Negative- LH from the pituitary stimulates the testis to produce testosterone which in turn feeds back to inhibit LH.
Positive- Less common, LH stimulation of oestrogen stimulates an LH surge at ovulation.
Describe the chronology of reproduction in women.
Oocytes stored, quiescent in ovaries whilst in the womb
Menarche at 12 years
Menopause at 51 years
Approx 468 reproductive cycles
What are the 4 main tissue types?
Epithelial
Connective
Sensory
Muscle
What is epithelial tissue?
One or a few layers of cells found on internal and external surfaces of organs, often lining body cavities mainly for protection e.g. columnar, squamous, stratified
What is connective tissue?
Tissue that support and bind structure together or are involved in storage/transport e.g. bone, cartilage, blood, lymph, adipose
What is sensory tissue?
Central and peripheral nervous systems e.g. nerve cells
Give examples of muscle tissues.
Striated
Smooth
Cardiac
How do connective tissues and epithelial tissues vary?
Connective tissues have sparse cells but lots of collagen, a large matrix. Epithelial tissues have the basal layer only but a large number of cells in sheets,
What are the three types of epithelial surface?
Simple columnar
Simple squamous
Transitional
What are the apical and basal surfaces of epithelia?
Apical- the external surface
Basal- internal surface, lower surface
What are the three major groups of cell junctions?
Occluding e.g. tight junctions
Anchoring e.g. actin/intermediate filament attachment sites
Communicating e.g. gap junctions
What are tight junctions?
They are present in between cells to act as a barrier to prevent leakage of unwanted molecules, sealing the membranes together. The more tight junctions, the stronger the seal.
What are the five pathways across the BBB?
Paracellular aqueous pathway Transcellular lipophilic pathway Transport proteins Receptor-mediated transcytosis Adsorptive transcytosis
What is the adhesion belt?
Actin filaments circulating around cells acting as an anchoring junction.
How are adhesion belts held together?
Cadherin proteins attach the belts together, it is an adherent protein that is dependent on calcium ions.
What is the importance of actin filaments and adhesion belt?
Development processes, neurulation. They allow epithelial sheets to change shape and form tubes.
What are desmosomes and hemi-desmosomes?
Allow intermediate (keratin) filaments to link cells with each other and with the basal lamina itself.
What is the role of gap junctions?
Gap junctions allow the free passage of molecules < 5000MWt between adjacent plasma membranes.
What are the features of a gap junction?
1.5nm in diameter, two connexons on adjacent cells line up to form a channel. Open in low calcium concentration or high pH.
What are the 6 stages of the body plan development?
Cleavage Blastula Gastrulation Neurulation Organogenesis Englargement
How do differences between cell phenotypes arise?
Precisely controlled gene expression.
What is stage 1 of the human body plan?
Cleavage- early rounds of cell division
What is stage 2 of the human body plan?
Blastula/blastocyst formation- hollow ball of cells
What is stage 3 of the human body plan?
Gastrulation- formation of the gut and GI system
What is stage 4 of the human body plan?
Neurulation- formation of the nervous system and skeletal system
What is stage 5 of the human body plan?
Organogenesis- formation of the organs, towards the end the formation of the reproductive system
What is stage 6 of the human body plan?
Enlargement, development, growth
How large is an oocyte?
1mm is diameter
Where does pigmentation occur within an oocyte?
In the cytoplasm of amphibia, especially where the cytoskeleton will form.
What is the animal pole of an oocyte?
The position where the upper organs form.
What is the vegetal pole of an oocyte?
The position where the lower organs form.
What is the dorso-ventral axis of an oocyte?
The dorsal side is the ‘back’ of the embryo- where the spinal cord will form. The ventral surface is the point of entry of the sperm and will form the front of the oocyte.
What is the proximal-distal axis?
Axis travels from the centre to periphery. Important in limb development.
When can a pregnancy test be effective?
The human chorionic gonadotrophin pregnancy test can detect the hormone 6-7 days after fertilisation.
What techniques are routinely used in IVF?
Ovarian hyperstimulation- produce multiple eggs
Ultrasound guided transvaginal oocyte retrieval
Egg and sperm preparation
Culture and selection of embryos
Transfer into the uterus around 3-5 days after fertilisation
What is the difference between the animal and vegetal poles?
Animal pole has small cells, vegetal pole has large cells
What are the three layers of the gastrula?
Outer ectoderm layer
Middle mesoderm layer
Innermost endoderm layer
How does the gastrula form?
A blastopore marks the point of invagination, causes some cells to be internalised, creating a multilayered structure.
How does neurulation occur?
The neural tube is formed by an infolding of the ectodermal layer along the dorsal surface. Microtubules cause elongation and actin filaments cause curvature
What is spina bifida?
Caused by the incomplete closing of the neural tube.
What is the role of the ectoderm in organogenesis?
Gives rise to the skin, nervous system and sensory organs.
What is the role of the mesoderm in organogenesis?
Gives rise to connective tissue such as skeleton, muscle, heart, vascular and urino-genital systems.
What is the role of the endoderm in organogenesis?
Gives rise to the gut, lungs, stomach, liver, pancreas and salivary glands.
When does sexual development occur in the foetus?
The embryonic body plan is initially female, until the genes on the Y chromosome are expressed, at around week 7.
At what stage is an embryo referred to as a foetus?
14 weeks
What is the Vas Deferens?
The tube between the testis and the seminal vesicle- location of vasectomy.
What is the Epididymis?
The joining between the testis and vas Deferens.
What is the seminal vesicle?
Adds an alkaline solution to sperm to form semen.
What happens to the prostate as males get older?
It hardens, putting pressure on the urethra, often making urine flow weaker.
Why are males less susceptible to UTIs?
They have a longer urethra, making it more difficult for E.coli to reach the bladder and their urethra is much further from the rectum due to its anatomy.
