Principles of Disease Overview Flashcards
What micro-organisms cause disease?
Bacteria Viruses Fungi Parasites Prions
For UTI’s what specimen is collected for culture?
Mid-stream urine sample
In chest infections what specimen is collected for culture?
Sputum
In Tonsillitis what specimen is collected for culture?
Throat swab
In diarrhoea what specimen is collected for culture?
Stool Sample
In bacteraemia what specimen is collected for culture?
Blood culture
In meningitis what specimen is collected for culture?
CSF sample
What does microscopy allow?
The staining and quick detection of bacteria
Can microscopy determine identify the type of bacteria?
No
What do cultures allow?
Bacteria to be grown and identified by looking at their visible appearances and their growth pattern
What is a sterile site?
A site that should not contain any micro-organisms
Give examples of sterile sites
Blood
CSF
Bladder
Lungs
What is a non-sterile site?
A site that can contain commensal microbes that may not harm the body but will show up in microscopy or culture
Give examples of non-sterile sites
Urethra
Gut
Skin
What type of microscopy detects viruses?
Electron Microscopy
What colour do gram negative bacteria appear?
Red
What colour do gram positive bacteria appear?
Purple
What shape are cocci bacteria?
Spherical
What shape are bacilli bacteria?
Rod shaped
What is the function of the flagellum?
Motility
What is the function of fimbriae?
Adherence
What is the lipopolysaccharide a component of?
The cell wall
What do PBP’s synthesise?
Peptidoglycans
What is the name of a bacteria based on?
The genus and species
Do strains of a species have similar or different characteristics?
Similar
What technique is used to identify strains of bacteria?
Typing
What are viruses classified according to?
Host range
Virion Structure and morphology
Structure and replication of virus genome nucleic acid
Why must cell cultures for viruses take place in cell lines, tissues or animals?
Because viruses require living cells to live
What percentage CO2 are viruses grown within?
2%
Give examples of viruses that can cause tumour?
HPV
Retrovirus
Hepatitis B
Give examples of viruses that can affect the respiratory tract?
Influenza
Rhinovirus
Give examples of viruses that can affect the GI tract?
Rota virus
Give example of viruses that can affect the neurological system/
Enterovirus
Herpes simplex virus
What brings about active immunity?
Brought about by a foreign antigen triggering an immune response
Does active immunity create immunological memory?
Yes
What is an attenuated vaccine?
One where the live organism is used
Give examples of attenuated vaccines?
MMR, BCG
What are inactivated vaccines?
One where the killed micro-organism is used
What is an acellular vaccine?
One where only the antigenic part of the vaccine is used
What is a toxoid vaccine?
One where a bacterial toxin is used
What is used to inactive the bacterial toxins in toxoid vaccines?
Formalin
What is a conjugate vaccine?
Links the antigens or toxoids of the microbe so that it can recognise the polysaccharide layer of certain bacteria
Wha does passive immunity involve?
Inoculating the patient with antibodies specific to the pathogen
Does passive immunity provide immunological memory?
No
What is human normal immunoglobulin?
Contains all antibodies from an unselected pool of random blood donors
What is human specific immunoglobulin?
Blood donors selected have a high antibody level against the target organism
What is an advantage of passive immunity?
It gives immediate protection
What are the 2 broad classes of gram positive cocci?
Streptococci
Staphylococci
What appearance do staphylococci have?
Clusters
What appearance do streptococci have?
Chains
What test is used on gram positive staphylococci?
Coagulase test
What bacteria is staphylococci coagulase positive?
Staph. aureus
What bacteria is staphylococci coagulase negative?
Staph. epidermis
What are the 3 classes of streptococci?
Alpha haemolytic
Beta haemolytic
Non-haemolytic
What bacteria are usually non-haemolytic?
Enterococci
What are the 3 classes of streptococci beta haemolytic?
Group A B and C
What are the 3 gram positive anaerobic bacilli?
Clostridium difficile
Clostridium Perfinges
Clostridium Tatani
Where are exotoxins released?
Extracellularly by the micro-organism
What are enterotoxins?
Exotoxins which act on the GI tract
What are endotoxins structurally part of?
The gram negative cell wall
What are the 3 virus pathogenic mechanisms?
Cell destruction following virus infection
Virus-induced changes to cellular gene expression
Immunopathogenic disease
Give an example of cell destruction following viral infection?
T4+ cells death by HIV
Give an example of virus0induced changes to cellular gene expression
Cellular transformation by tumour viruses
Give an example of an immunopathogenic disease?
Influenza A
What is MIC?
The minimal inhibitory concentration - min conc. of antimicrobial needed to inhibit visible growth of a given organism
What is MBC?
The minimal bactericidal concentration - min conc. needed to kill the given organism
What is sensitive?
When the organism is killed or inhibited by given levels of the antimicrobial
What is resistant?
When the given organism is not killed or inhibited by the levels of antimicrobial
What is a bactericidal?
An antimicrobial that kills bacteria
What is a bacteriostatic?
An antimicrobial that inhibits the growth of a bacteria
What are the three mechanism that antibiotic use to combat bacteria?
Inhibit the synthesis of the cell wall
Inhibit the synthesis of nucleic acid
Inhibit protein synthesis
What are the two groups of B lactams?
Penicillin
Cephalosporin
What are the 2 groups of antibiotics that inhibit the synthesis of the cell wall?
B lactams
Glycopeptides
What was the original penicillin?
Benzyl penicillin
Give 2 examples of glycopeptides?
vancomycin
teicoplanin
What is vancomycin best for treating?
Gram negative bacteria
Who is vancomycin not suitable for?
Children
What are potential causes of acute inflammation?
Micro-organisms Mechanical trauma Chemical changes Extreme physical conditions Dead tissue - necrosis Hypersensitivity
What happens to the blood vessels in inflammation?
Initially the vessels constrict - for protective reasons
Then the vessels dilate
What does vasodilation cause?
An increase in blood flow to the area
What is the triple response?
Flush, Flare Wheal
What cells are involved in acute inflammation?
Neutrophils
What happens to vessel permeability in acute inflammation?
There is an increase in vessel permeability
What is exudation?
When there is movement from plasma into the ECM of plasma and proteins
Give examples of proteins that are in the exudate
Fibrinogen
Immunoglobulin
What is fibrin?
A clotting factor
A polymer of fibrinogen
What oedema?
The accumulation of exudate in the ECM
What does oedema cause?
Swelling reducing function and causing pain
What is margination?
Neutrophils move to the endothelial aspect of the lumen
What is Pavementing?
When neutrophils adhere to the endothelia
What is emigration?
When the neutrophils squeeze between endothelia to the outside tissue
What are the systemic effects of acute inflammation?
Pyrexia
Malaise
Neutrophilia (increased WBC)
Septic shock
What is angiogenesis?
When blood vessels form at the site
Why do capillaries grow into the inflammatory mass?
To allow the access of plasma proteins, macrophages and fibroblasts
What does granulation tissue eventually form?
A scar
What is bacteriamia?
When there is bacteria in the blood
What is septicaemia?
When there is the growth of bacteria in the blood
What is toxaemia?
When there are toxins in the blood
What cell types are involved in chronic inflammation?
Lymphocytes
Macrophages
Plasma Cells
Fibroblasts
What are the 2 major causes of chronic inflammation?
Progressing from acute inflammation
Arising as a primary lesion
How does chronic inflammation arise from acute inflammation?
When there is a large volume of damage
There is the inability to remove the debris
Their is failure of the acute inflammation to resolve
When chronic inflammation arises from a primary lesion is there any acute phase?
No
What can primary chronic inflammation occur as a result of?
Autoimmunal disorder
Material resistant to cellular digestion
Exogenous substances
Endogenous substances
What factors can promote the healing and repair of chronic inflammation?
Cleanliness
Apposition of edges
Sound nutrition
Normal inflammatory and coagulation mechanisms
What factors can impair the healing and repair of inflammation?
Dirty gaping wounds
Poor nourishment (of vitamins ect)
Inhibition of angiogenesis
What Ab does type I hypersensitivity involve?
IgE
What is Type I Hypersensitivity commonly known as?
Allergy
What cells respond in type I hypersensitivity?
Mast cells
What happens during sensitisation in type I hypersensitivity?
The allergen is shown to T helper cell by an APC
This causes B cells to differentiate to produce IgE against the antigen
What happens onwards from sensitisation in Type I hypersensitivity?
The bodies exposure t the antigen will cause the release of cytokines from mast cells causing an allergic response
Which antibodies are involved with type II hypersensitivity?
IgG and IgM
What is type II hypersensitivity hard to distinguish from?
Autoimmunity
Why is type II hypersensitivity hard to distinguish from autoimmunity?
Because the bodies antibodies bind to the antigens on its own cel surfaces
What are formed in type III hypersensitivity?
Immune complexes
What are immune complexes?
Clumps of antibodies that have stuck together
Where do the immune complexes go in type III hypersensitivty?
They are deposited in tissues
What is the effect of deposited immune complexes in the tissue?
Inflammation
What recognises the antigens in type IV hypersensitivity and what do they produce when recognised?
CD4 helper T cells
Produce cytokines
What is the substance with the low m.w in type IV hypersensitivity known as?
Hapten
What is the hapten combined with?
Carrier protein
Why is the hapten combined with a carrier protein?
To produce sufficient antigenic bulk
What is an early phase response?
A response that occurs within minutes
What mechanism is used in early phase response?
The chemicals used are preformed in mast cells (histamine, heparin, chemotactic factors)
What mechanism is used in late phase response?
Newly synthesis mediators are involved
What is the effect of localised immune complex formation in type III hypersensitivity?
Local inflammation
What happens when there is systemic immune complex formation in type III hypersensitivity?
Complexes are deposited in tissues and organs such as the skin, joints, blood vessels and kidneys
What is an autoimmune disease?
A large group of clinical disorders by tissue organ damage mediated by incorrect immune mechanism targeted at self antigens
What factors are involved in the aetiology of autoimmune diseases?
Genetic factors
Hormonal factors
Environmental factors
Immune regulatory factors (the immune system is not working correctly)
What are the pathogenic mechanisms involved in autoimmune disease?
Cell mediated Antibody mediated Antibody + complement Immune-complex mediated Recruitment of innate compounds
Give an example of an autoimmune disease of joints
Rheumatoid Arthritis
What are the 3 main types of parasites?
Protozoa
Helminths
Arthropods
Give examples of arthropods
Ticks
Lice
Mites
What is the vector of malaria?
Female mosquito
Gives three examples of protozoa parasites
Malaria
Amoebic Dysentery
Leishmaniasis
Give an example of helminths
Tape worm
Nematodes
In malaria what are injected under the skin?
Sprozoites
Where do sprozoites travel to and mature (malaria)?
Travel through the blood to the liver where they mature
When sprozoites have matured what do they re-enter the blood stream as?
Merozoites
What do merozoites in malaria go?
Re-enter circulation
Invade and destroy RBC
Is there any cure for malaria?
No
What is the side effect of amoebic dysentery?
Diarrhoea with blood and pus
How many species of leishmaniasis are there?
Several
What do leishmaniasis causes?
Skin and mucosal ulceration
What does visceral leishmaniasis cause?
Fever, weight loss
What is leishmaniasis spread by?
Spread by sandfly bites
What occurs in late disease amoebic dysentery?
Liver abscesses
How do trophoziote ingest red cells?
By pseudopodia
Give an example of a trematode worm?
Schistosomiasis
Where are the eggs secreted in schistosomiasis?
Urine or faeces
What is the intermediate host in schistosomiasis?
Snail
In schistosomiasis what emerges from the snail 4-6 weeks later?
Cercaria
What is the definitive host in schistosomiasis?
Humans
Where does schistosomiasis migrate in humans?
Lungs to liver
Give examples of organ specific autoimmune diseases
Thyroid - thyrotoxicosis
Stomach - pernicious anaemia
Adrenal - addisons disease
Give examples of non-organ specific autoimmune diseases
Muscles - dermatomyositis
Skin - scleorderma
Kidneys - SLE
Joints- rheumatoid arthritis
Do drugs have to be lipophobic or lipophilic to cross the membrane?
Lipophilic
Why do drugs have to resemble the naturally occurring substance in active transport?
So they fit through the pumps by having a similar conformation to the naturally occurring molecule
Do highly lipid soluble drugs diffuse through the membrane?
Yes - readily
What do small changes in pH affect in drugs?
The ionisation and solubility
Do ionised drugs cross the membrane?
No
What happens to un-ionised drugs at the membrane?
They distribute across the membrane until equilibrium is reached
What factors affect the absorption of a drug in the GI tract?
Motility
Food
Illness
What is the effect of food on the absorption of a drug from the GI tract?
Can impair or enhance the action of the drug
What is the effect of motility on the absorption of a drug in the GI tract?
Will affect the speed at which the drug will reach the site of absorption
How do migraines affect the absorption of a drug from the GI tract?
Reduces the rate of stomach emptying
What is first pass metabolism?
The metabolism of the drug prior to it reaching the site of absorption
Where does first pass metabolism mainly occur?
Gut Lumen
Gut Wall
Liver
What is the bioavailability of a drug administered IV?
100%
Does IV have first pass metabolism?
No
Where are inhaled drugs mainly metabolised?
Lungs
Are small or large doses used in inhalation drugs?
Small doses
Is there much systemic absorption of drugs administered by inhalation?
Little systemic absorption
Does topical administration achieve local or systemic effects?
Both
Does topical administration go through first pass metabolism?
Yes
What is the bioavailability of a drug?
The amount of drug which reaches the circulation and is available for action
What affects a drug ability to cross the membrane?
Particle size
Lipid solubility
pH and ionisation
What factors determine the bioavailability of a drug?
Formulation
Drugs ability to pass physiological barriers
Gastrointestinal effects
First pass metabolism
Give an example of a plasma protein that a drug binds to?
Albumin
If a drug is bound to protein is it active?
No
Is plasma protein binding of a drug reversible?
Yes
For plasma protein binding to be important what percentage of the drug must be bound?
90%
What affects drug distribution?
Plasma Protein Binding Tissue Perfusion Membrane Characteristics Transport Mechanisms Diseases/Other Drugs Elimination
What 3 reactions are involved in phase 1 metabolism?
Hydrolysis
Oxidation
Reduction
What does phase 1 metabolism increase?
The polarity of the compound
What does phase 1 metabolism provide for phase 2 metabolism?
An active site
What family of enzymes carry out phase 1 metabolism?
P-450
What are the 3 P-450 enzymes involved in phase 1 metabolism?
CYP3A4
CYP2D6
CYP1A2
Where is CYP3A4 found?
In the human layer
Give examples of drugs that are metabolised by CYP3A$
Diazepam
Methadone
Simvastatin
What does CYP2D6 metabolise?
Antidepressants, antipsychotics
What does CYP2D6 convert codeine to?
Morphine
In what percentage of the population does CYP2D6 have reduced expression?
5-10%
What is CYP1A2 induced by?
By smoking
What does phase 2 involve?
Conjugation
What does conjugation do?
Increases the water solubility of a compound
Why is increasing water solubility in conjugation important?
Makes secretion easier
What does phase 2 involve the attachment of to the metabolite from phase 1?
Glucuronic acid
Gluthianone
Sulphate
Acetate
Are all drugs inactivated by conjugation?
No but most are inactivated
What is enzyme induction in drug metabolism?
Many of the metabolising enzymes can be induced by other substances
What is the effect of enzyme induction?
More metabolising enzymes
Decreased drug effect
What are the most common inducers of metabolising enzymes?
Alcohol
Smoking
What does ethnicity affect in terms of drug?
Rarely they affect drug metabolism
How does genetics affect drug metabolism?
Drug metabolising enzymes are often expressed in different forms so differences in individual gene expression is common
Describe metabolising enzymes in foetuses and premature infants
The metabolising enzymes are often or reduced
Describe the renal function in premature infants and foetuses and its effect on drug metabolism
Renal function is deficient - which can lead to a build up of the drug - toxicity
By the age of 2 describe drug metabolism/
Drugs are metabolised faster than in adults
Describe enzyme inhibition in drug absorption
many commonly used drugs can inhibit the metabolising enzymes
Where are enteric tablets broken down?
In the small instetine
Why are tablets coated with enteric coating?
To protect the tablet from the stomach acid
To prevent the stomach from the drug
What are the benefits of tablets and capsules?
They are convenient
They have an accurate dose
They have an ease of mass production
Are solutions/suspensions absorbed rapidly?
Yes
What does the absorption of solutions and suspensions depend on?
Gastric emptying
What drugs are suspensions good for?
Insoluble and unpalatable drugs
What percentage of inpatients suffer ADR’s?
10-20%
What percentage of hospital deaths are due to ADR’s?
0.25-3%
How many deaths per year are caused by drug ADR’s?
5000-10000
What percentage of hospital admissions are due to ADR’s?
6.5%
What do A ADR’s stand for?
Augmented
Describe type A ADR’s
Predictable
Dose dependent
Resolve when the drug is stopped
They ADR have been recognised before the drug is available
What does type B ADR’s stand for?
Bizarre
Describe type B ADR’s
Unpredictable
Rare
Can cause serious illness or death
It is unrelated to dose
What does type C ADR’s stand for?
Chronic
Describe type C ADR’s
They are related to dose
They are related to the length of treatment
It is semi-predictable
What does type D ADR’s stand for?
Delayed
Describe type D ADR’s
They occur years after treatment or in the children of the patient
What does type E ADR’s stand for?
End of treatment
Describe type E ADR’s
The effects causes when the dug treatment is stopped - especially suddenly (like withdrawal symptoms)
What does type F ADR’s stand for?
Failure of treatment
Describe type F ADR’s
They are common
Frequently caused by drug interactions
What factor may predispose a patient towards drug-drug interactions?
Number of drugs on
The patients age
Wether the patient has a critical illness
Wether the patient is undergoing surgery
Whether the patient already has a chronic underlying condition
What is a drug interaction?
Defined as the modification of a drugs effect by prior or concomitant administration of another drug, herb, food or drink
What are the different types of drug interactions?
Drug interactions Herbal interactions Food interactions Drink interaction Pharmacogenetics interactions
What is the object drug?
The drug whose activity is effected by such an interaction
What do clinical test provide?
Evidence
What are the two reasons that drugs need to be tested?
For their efficacy (if they work)
For their safety ( are they safe)
What is the exclusion criteria in drug trials?
Pregnant women
Children
Elderly
Seriously ill
What factors have to be taken into consideration when choosing patients for clinical trials?
Age
Race
Compliance
Sex
What are the control group given in a clinical trial?
Placebo
What do you compare a drug in a clinical trial with to test its efficacy?
A placebo
With another drug
What basics have to be taken into consideration when doing a drug trial?
The time scale The end result The choice of control drug The choice of patients The exclusion criteria The drug used
What do we have to consider about the drug used in a clinical trial?
Formulation of the drug
Dose of the drug
Frequency that the drug is given
What is a double blind trial?
Neither the doctor knows which of the drugs the subjects are getting (the drug or the control drug)
What is a single blind clinical trial?
When the patient doesn’tknow if they are receiving the drug or control but the doctor does know
What is a randomised clinical trial?
When the patients are assigned to a group at random to prevent bias
What is a placebo controlled clinical trial?
When half the subjects get basically nothing and the other half get the drug
Comparisons are made at the end of the trial
How many patients does Phase III of a clinical trial involve?
1000-3000
How many subjects does Phase I of a clinical trial involve?
100
How many subjects does a type II clinical trial involve?
Up to 500
What is a pilot study?
To test the design of the study
What are the disadvantages of a randomized control clinical trial?
Subjects may not represent general patient population
Twice as many people are needed for the study
Some physicians will refuse
Some patients will refuse
What is a superiority design?
Shows that the new treatment is better than the control or standard
How long can it take to get a chemical structure to a licensed drug?
10 years
What drugs will bypass phase I of the trial?
Cytotoxics
What type of subjects does phase I of a clinical trial use?
Volunteers
What does Phase II of a clinical trial confirm?
The kinetics and dynamics in patients
What does Phase III of a clinical trial establish?
The efficacy
Evidence of safety will also be established
What does Phase IV of a clinical trial produce evidence for?
Long term safety
What does p<0.05 mean?
It means that there’s less than a 5% chance your results were obtained by random chance or error
What shape does DNA have?
Double helix
What does a DNA nucleotide consist of?
Pentose sugar
Phosphate
Base
In what direction do the strands run in DNA?
One strand runs 5’ to 3’
One strand runs 3’ to 5’
What does DNA replication issemi-conservative and bi-directional mean?
That one half of each DNA molecule is old and the other half is new
Are DNA strands created in the same or different direction?
Different
In what direction are DNA strands created?
In a 5’ to 3’ direction
Which enzyme unzips the DNA?
DNA Helicase
What enzyme adds new nucleotides in DNA replication?
DNA polymerase
Which enzyme joins the DNA fragments in the 3’ to 5’ strand?
DNA ligase
What is each set of 3 bases called?
Codon
What does each codon code for?
Amino acid
How many amino acids are there?
20
How many codon combinations are there?
64
Does one amino acid refer to one codon?
No more than one codon can refer to one amino acid
What amino acid has only one possible codon?
Methionine
What is the initiation codon of transcription?
Methionine
What codon stops transcription?
The termination codon
The process of introns being removed and exons remaining in tact is known as what?
RNA splicing
What sections of the RNA are spliced out?
Introns
What sections of the RNA are coding and so remain intact?
Exons
Once the mRNA has been produced what is added to the 5’ end?
A cap
Once the mRNA has been produced what is added to the 3’ end?
A tail
Where does translation occur?
Endoplasmic reticulum
What does tRNA stand for?
Transfer RNA
What is a germline mutation?
An inheritable mutation of gametes
What is a somatic mutation?
A mutation of the other body cells which wont be passed onto future generations
What is a silent mutation?
When one of the bases has be substituted but the codon still codes for the same amino acid meaning nothing has been changed in the sequence
What is a missense mutation?
When the correct amino acid is replaced by an incorrect amino
The polypeptide makes some sense but not the original sense 1
What is a nonsense mutation?
When the correct amino acid is replaced by a stop codon
There is premature ending of the polypeptide sequence and it makes no sense
What is a frameshift mutation?
When a base is inserted or deleted
Consequently this cause all codons to shift
The whole sequence is changed
In what sections of chromosomes is DNA expressed?
Euchromatin
In what denser sections is the DNA inactive?
Heterochromatin
What proteins is DNA wrapped around?
Histone
What charge do histone proteins carry?
Positive
The DNA wrapped around histone forms what?
Nucelosomes
What are the tips of the arms of chromosomes called?
Telomeres
What are the 6 stages of mitosis?
Interphase Prophase Metaphase Anaphase Telophase Cytokinesis
What is mitosis?
The separation of the nucleus
What is cytokinesis?
The separation of the cytoplasm
What happens in prophase?
Chromosomes condense
Nuclear membranes disappear
Spindle fibres form from centrioles
What happens in metaphase?
Chromosomes align at the equator of the cell
Attached by microfilaments to each centriole
Here there is maximum condensation of the chromosomes
What happens in anaphase?
Sister chromatids separate at the centromere
Separate longitudinally
Move to opposite ends of the cell
What happens in telophase?
New nuclear membrane form
Each cell has 46 chromosomes
What happens in cytokinesis?
The cytoplasm separates
Forming 2 new daughter cells
How many sperm cells are formed per meiotic cycle?
4
Is there a higher chance for eggs or sperm to have mutations and why?
Sperm
Because they undergo many more divisions than eggs
What is spermatogenesis?
The process of sperm production
When does spermatogenesis commence?
In puberty
What is oogenesis?
The process of egg division
When does oogenesis occur?
In early embryonic life
What is trisomy 21 more commonly known as?
Down’s syndrome
With advancing age does chances of trisomy 21 increase or decrease?
Increase
What is trisomy 13 more commonly known as?
Patau Syndrome
What is trisomy 18 more commonly known as?
Edwards syndrome
What is the disease with one X chromosome?
Turner syndrome
What is the disease with XXY sex chromosomes?
Klinefelter snydrome
What is the prognosis for Edwards syndrome?
Most die within the first year or months of life
What is the prognosis for patau syndrome (trisomy 13)?
Very few survive beyond the first year of life
What is a trisomy mutation?
When there are 3 copies of the chromosome
What is a deletion mutation?
When a part of the chromosome deletes
What are the two types of inversion mutations?
Paracentric
Pericentric
What is a paracentric mutation?
When a section of the DNA in the arm of the chromosome is inverted
What is a pericentric inversion mutation?
When a section of the DNA is inverted around the centromere of the chromosome
What is a robertsonian translocation mutation?
When one of the chromosomes ends up with 2 long arms
When the other chromosome ends up with 2 short arms
What 2 groups of antibiotics inhibit the synthesis of the cell wall?
B lactams
Glycopeptides
What are the 2 groups of B lactams?
Penicillin
Cephalasporin
What are the 2 groups of glycopeptides?
Vancomycin
Teicoplanin
What was the original penicillin?
Benzyl penicillin
What is a common problem with vancomycin?
Toxicity
Do gylcopeptides act on gram positive or negative?
Gram positive
What are the 4 groups of protein synthesising inhibitor antibiotics?
Aminoglycosides
Macrolides/Tetracyclines
Cyclic Lipopeptide
Oxazolidinones
Are aminoglycosides especially useful in the treatment of gram negative or gram positive bacterial infections?
Serious gram negative
What are macrolides a useful alternative to?
Penicillin - those with allergies
What is an autosomal condition?
One which affects any chromosome other than the sex chromosomes
How many copies of the affected gene are required to be affected in autosomal recessive conditions?
2
How many copies of the affected gene are required to be affect in autosomal dominant conditions?
1
In autosomal dominant inheritance which generations are affected?
Each generation is affected
In autosomal recessive inheritance which generations are affected?
Generations are usually skipped
What is the chance of inheriting the mutation in autosomal dominant?
50%
Why are X linked recessive conditions more prominent in men?
Because they do not have a second X chromosome to mask the affected gene
Who does Y linked inheritance affect?
Males only
Where does all mitochondrial DNA come from?
Maternal origin
Where does mitochondrial disease come from?
Maternal origin
What is P?
Dominant
What is Q?
Recessive
What are the factors assumed in an idea population of genetics?
Mutations are ignored Migration is negligible Population size is large Mating is random There are no selective pressures
In genetics why is the expected not always the same as the observed?
Because fertilisation is a random process
What does the classification of a tumour depend on?
The region where it is found
If it is benign or malignant
What is a glandular benign tumour called?
Adenoma
Does mitosis involve recombination?
It can
What are the major eukaryotic histone proteins
H2A, H2B, H3 H4
What do fibroblasts do?
Produce collagen
What does histamine promote?
The relaxation of smooth muscle
Where do neutrophil polymorphs have a major role?
In acute inflammation
What is hypoxia?
Lack of O2 to tissues
What does hypoxia impair?
The healing of tissue
What two aspects of the human skeleton are useful in identifying sex in skeletonisation?
Skull and pelvis
How is the age of the dead approximated in children?
Assessment of the epiphyses
What bones are the most useful for the calculation of height?
Lower limb
What information can be useful for personal identification?
Fingerprints
Dental records
DNA
For the terms of this what is death defined as?
The irreversible failure of the cardiovascular system
When the cardiovascular system fails what happens?
There is failure of O2 delivery resulting in tissue death
There is no blood pumping
The immune system ceases
What is the best opportunity for timing of death?
First 18 hours
What is the rule of thumb for the cooling after death?
1 degree per hour
What is rigor mortis?
The stiffening or shortening of muscle fibres leading to the rigidity of the muscles and the fixation of the joints
Is there any particular method that is good for determining time of death?
No
What does hypostasis represent?
The pooling of stagnant blood in dependant regions of the body under the influence of gravity
What is putrefaction?
Caused by the action of bacterial micro-organisms when the organism start to decay away at the body
Who is more affected in X-linked recessive inheritance?
Males more than females
Why are males more affected in X-linked recessive inheritance?
Because they only have one copy of the X chromosome
Why can males not transmit X linked recessive to sons?
Because males pass on their Y chromosome to sons
Why can males not transmit X linked dominant to sons?
Because males pass on their Y chromosomes to sons
In autosomal dominant inheritance what is the chance of inheriting the mutation?
50%
Who does Y linked inheritance affect?
Males only
Why does Y linked affect males only?
Because only males have a Y chromosome
What is mitochondrial inheritance disease a form of?
Maternal inheritance
Why is mitochondrial disease a form of maternal inheritance?
Since all mitochondrial DNA comes solely from the mother
What is anticipation?
The diseases are spotted in earlier generations and increase with severity in later ones
What is genetic penetrance?
The frequency with which a trait is manifested by individuals carrying the gene
With the gene CFTR and the disease cystic fibrosis what is the penetrance?
100%
With the gene BRCA1/2 and the disease breast cancer what is the penetrance?
70-80%
With the gene BRCA1/2 and the disease ovarian cancer what is the penetrance?
50%
What is cystic fibrosis caused by?
A mutation in CFTR
What environmental can affect the severity of disease?
Lifestyle Diet Smoke Alcohol Drugs Stress Air pollution Chemicals Infection
What is epigenetic modifications?
Heritable changes in gene function that cannot be explained by changes in DNA sequence
Why are mitochondria a mutation hotspot?
Lack of efficient DNA repair system
Lack of protective proteins such as histones
Damaged by reactive oxygen species
100-fold higher than nuclear genome
Give examples of anticipation diseases?
Huntington’s disease
Myotonic dystrophy
Fragile X syndrome
Describe myotonic dystrophy
Autosomal dominant disorder
Severe distal muscle weakness
Age of onset decreases with successive generations
Learning difficulties
What are proto-oncogenes?
Genes that code for cell growth and regulation
What are oncogenes?
They do not regulate growth and just accelerate it forming a tumour
What is a tumour suppressor gene?
Genes that act as the brakes for cell growth
How do tumour suppressor genes act as brakes for cell growth?
They can inhibit the cell cycle
Or promote apoptosis
Describe the double hit hypothesis
Both a proto-oncogene and tumour suppressor gene are hit by mutations
What are the purine bases?
Adenine
Guanine
What are the pyrimidines bases?
Thymine
Cytosine
