Keeping People Healthy: Week Two Flashcards
What are the three main types of single gene mutations?
- Autosomal dominant
- Autosomal recessive
- X-linked recessive
There is a vertical pattern with many generation affected. Is the condition dominant or recessive?
Dominant
There is a horizontal pattern. Is the condition dominant or recessive?
Recessive
When there are both females and males affected, is this autosomal or x-linked?
Autosomal
When there is male to male transmission, s this autosomal or x-linked?
Autosomal
What is the knights-move inheritance?
This is when two males are affected through an uninfected female. There are only males affected and this is X-linked recessive.
What are some symptoms of Down Syndrome?
- upward slanting of eyes
- small nose
- low set ears
- learning difficulties
- higher incidence of conditions like heart problems
What is triploidly?
Three sets of chromosomes
What is XXY?
Klinefelter syndrome
What is the chromosome arrangement in Klinefelter syndrome?
XXY
What is triple X syndrome?
XXX
What is the definition of malformation?
This is a structural abnormality causes by an abnormal process that is intrinsic to development.
Give an example of a malformation
Spina Bifia
What is the definition of Disruption?
This is a defect in the body causes by a process that interferes with the normal development.
Give an example of a disruptive disease
Thalidomide induced
What is the definition of Deformation?
This is a structural deformity caused by mechanical forces
What is an example of deformation?
Amniotic band constriction
What does thalidomide affect during pregnancy?
Limb development
What does tetracycline affect during pregnancy?
Tooth enamel
What does streptomycin affect during pregnancy?
Inner ears
What does methotrexate affect during pregnancy?
Craniofacial development
What kind of drug is methotrexate?
DMARD
What condition is caused when a pregnant women is dependent on alcohol?
Fetal alcohol syndrome
Why is screening done?
This is done to identify individuals who are more likely to be helped rather then a harmed by further tests or treatment. Screening uses a defined population.
What group of people get AAA screening?
Men aged 65
What group of people get diabetic retinopathy screening?
Diabetics over 12
What is the best method for monitoring the effectiveness of a screening programme?
Randomised controlled trials
What are some pitfalls in studying screening effects?
- healthy volunteer bias
- Lead time bias
- Length time bias
What is Lead time bias?
Survival period is perceived to be a lot longer
What is length time bias?
The tests are more likely to diagnose slow-growing tumours and these have a longer survival rate
What is sensitivity?
The test identifying people with the condition
What is specificity?
The test identifying people without the condition
What is positive predicted result?
How likely the positive result is true
What is negative predicted result?
How likely the negative result is true
What are some potential harms of screening programmes?
- false positive and false negatives
- over diagnosis and treatment
- resource allocation and opportunity costs
- exacerbating inequalities
What is the meaning of malnutrition?
This is a condition that results from eating a diet in which nutrients are either too much or not enough
What is food insecurity?
A state of being without reliable access to a sufficient quality of nutritious food
What are some factors contributing to under-nutrition in the elderly?
Physiological: illness
Social: difficulties accessing foods, affording foods, inability to prepare food, social isolation
What is the definition of severe acute malnutrition?
Below 3 stranded deviation of median weight for height, visible severe wasting or nutritional oedema
What is the definition of moderate malnutrition?
Weight loss and 2-3 standard deviations for median weight of height
What is the definition of mild malnutrition?
Weight loss and 1-2 standard deviations below median weight for height
Name the determinants of heath and well-being
- people
- lifestyle
- community
- local economy
- activities
- built environment
- natural environment
- global ecosystem
What factor is vWF bound to and what is the function of this?
vWF is bound to factor 8 and this allows factor VIII to be inactive. Factor VIII released by thrombin action.
Are mutations in the germ line inherited or non-inherited?
Inherited
Are mutations in the somatic cells inherited or non-inherited?
Non-inherited
What is the disposable soma aging theory?
DNA repair activity is much higher in the germ line and higher in terms of energy. Soma is less important and mutations rates are higher, therefore, cells will accumulate DNA damage and die.
What are two consequences of DNA damage?
Cancer and Aging.
What carries out DNA unwinding during replication?
DNA helicase
What enzyme mediates DNA replication and what ends does it travel from?
DNA polymerase mediates DNA replication and goes from the 3’ - 5’ end.
What enzyme follows DNA polymerase and functions to detect any DNA damage?
DNA mismatch repair complex.
What happens with DNA mismatch repair complex detects DNA damage?
The DNA mismatch repair complex will send signals to DNA polymerase to stop activity. DNA exonuclease will be recruited and this cuts the new daughter strand until the damage has been removed.
What cancer is common from a mutation in the DNA mismatch repair complex?
Non-polyposis colon cancer
Give four examples of DNA damage
- base modification
- base loss
- single stranded break
- double stranded break
Give an example of endogenous mutagens
Hydrogen peroxide
What mutations do x-rays cause?
Double-stranded breaks
What mutation does UV radiation cause?
Thymidine dimerization
Explain the function of Nucleotide excision complex
This complex detect DNA damage. This complex is made up of many different subunits and each part is specialised for a certain damage. They will bind to damage and recruit DNA endonuclease.
DNA endonuclease will make a single-stranded cut and remove the DNA damage. DNA polymerase will then be recruited to replace the bases.
Name two conditions where there is defective nucleotide excision repair complex
- xeroderma pigmentosum
- cockayne syndrome
What are some symptoms of xeroderma pigmentosum?
There is a high risk of skin caner. There is accelerated aging and dwarfism.,
What are some symptoms of cockayne syndrome?
There is accelerated aging and dwarfism.
What are the two methods for repairing double-stranded breaks?
- homology dependent
- non-homology end-joining
Explain the method of homology dependent method of repairing double stranded breaks
An endonuclease is recruited and this exposes the DNA damage. The sister chromatid is recruited and replication occurs. This process requires energy but is very reliable as no information is lost. This occurs in germ-line cells.
Explain non-homology end-joining
This occurs more in somatic cells. DNA that is damaged is removed and two ends, where the DNA has been removed, join together. This means that information is lost.
What chromosomes are involved in the Philadelphia chromosome translocation?
9 and 22
What condition does the Philadelphia chromosome translocation cause?
Chronic Myelogenous Leukaemia
What chromosome is ABL located on?
Chromosome 9
What chromosome is BCR on?
Chromosome 22
Explain the pathology of Philadelphia chromosome translocation?
A trigger causes a translocation mutation where ABL, located on chromosome 9, is switched to chromosome 22. This crates the fusion-gene, BCR-ABL. This causes uncontrolled growth of the myeloid cells.
What is Nijmegen breakage syndrome?
This is an autosomal recessive condition where there is defective homologous dependent repair system.
What genes are mutated in inherited breast and ovarian cancer?
BRCA1 and BRCA2 (these are involved in homology dependant repair.
Describe the two pathways that damaged DNA can go through
- Little DNA damage allows repair
- High DNA damage causes apoptosis
What is the difference between vaccine and immunization?
Vaccine: induced immunity through vaccine
Immunization: vaccine induced immunity and antibody transfer
What are some aims of immunization?
- to protect those at risk
- eradicate or contain a disease
What is the definition of eradication?
Disease and causative agent removed worldwide
What is the definition of Elimination?
Disease removed from WHO region
What is the definition of Containment?
Disease no longer gives significant health problems
What is the function of Th1 cells?
Macrophage recruitment
What pathogens do antibodies deal with?
Extra-cellular
What pathogens do T cell deal with?
Intra-cellular
What happens to adverse effects of live vaccines when the dose increases?
Frequency falls
What happens to adverse effects of inactivated vaccines when the dose increases?
Frequency increases
What are live vaccines?
These are attenuated stains which replicated in the host. They induce long lasting immunity and has a strong immune response. There is poor stability and it can revert to virulence.
What are inactivated vaccines?
These are stable vaccines that has either the whole organism, acellular component of the organism or a recombinant version. They can’t cause disease but give a shorter-lasting immunity.
Name six components of vaccines
- active components
- stabilizers
- trace components
- antibiotics
- preservatives
- adjuvants
What is the active component of a vaccine?
This is a modified antigen that produces an immune response but no disease.
What is the adjuvant component of a vaccine?
These enhance a body’s immune response by keeping the antigen to one area.
What is the antibiotic component of a vaccine?
These are used in the manufacturing process to prevent contamination.
What is the stabilizer component of a vaccine?
Added to ensure various components remain stable and effective.
What is the preservative component of a vaccine?
Prevent contamination
What are the trace components of a vaccine?
These are left-over form the manufacturing process and there is a very low concentration in it.
What is herd immunity?
This is where there is a certain level of immunity in a population that can protect the entire community. Herd immunity provides indirect protection of unvaccinated individuals.
What is the effective reproductive number?
The effective reproductive rate (R) estimates the average number of secondary cases per infectious case in a population made up of both susceptible and non-susceptible hosts.
What is the basic effective number?
The basic reproduction rate (R0) is used to measure the transmission potential of a disease.
What does it mean when R0 is >1 and <1?
R0<1 = no sustained transmission R0>1 = epidemic possible
What is the causative agent of Pertussis?
Bordetella pertussis
What is whopping cough?
Pertussis (whooping cough) is caused by Bordetella pertussis, a small Gram-negative coccobacillus that infects the mucosal layers of the human respiratory tract. It is transmitted from infected to susceptible individuals through respiratory droplets. After an incubation phase of 7-10 days patients develop nose and throat inflammation and cough, and in the course of 1-2 weeks coughing spasms ending in the classical ‘whoop’ may occur. Bronchopneumonia, causing relatively high mortality, is the most prominent problem associated with pertussis
What are the two types of vaccines offered for Pertussis (whooping cough) ?
Two forms of vaccine are in use, the whole-cell vaccine (wP), and the acellular vaccine (aP).
What are the characteristics of the whole-cell vaccine for pertussis?
Whole-cell pertussis vaccines were developed first and are suspensions of the entire B. pertussis organism that has been inactivated, usually with formalin. Most wP vaccines are available in combination with diphtheria (D) and tetanus (T) vaccines, contain aluminum salts as an adjuvant and, thiomersal as a preservative. Immunization with wP vaccines is effective and the vaccine is relatively inexpensive, but immunization has been frequently associated with minor adverse reactions such as redness and swelling at the site of injection, along with fever and agitation. Local reactions tend to increase with age and the number of injections; wP vaccines are therefore not recommended for immunization of adolescents and adults.
What are the characteristics of the acellular vaccine for pertussis?
To address the adverse reactions observed with the whole-cell vaccines, aP vaccines were developed that contain purified components of B. pertussis such as inactivated pertussis toxin either alone or in combination with other B. pertussis components such as filamentous haemagglutinin, fimbrial antigens and pertactin.
What is passive Immunity?
This is where someone gets someone else’s antibodies.
What are the characteristics of passive immunity?
They provide immediate but temporary protection.
What are some sources of antibodies for passive immunity?
- human pooled blood
- monoclonal
- animal sources
What are some global immunization challenges?
- funding
- surveillance
- different priorities
- multiple agencies
- mistrust and suspicion
- violence and crime
What happens to the positive predicated value when a condition becomes less problematic?
It decreases
Which sample would be give the preferred type (i.e. gives the highest sensitivity for the lowest risk) for screening programme for Down Syndrome?
First trimester blood test
Name two examples of protein energy malnutrition
Marasmus and Kwashiorkor
Is albinism dominant or recessive?
Recessive
IS cystic fibrosis dominant or recessive?
Recessive
What are the pedigree characteristics of Duchenne muscular hypertrophy?
Childhood onset
Only males affected
Knight-move
Where does the neural plate form?
Cranial end from the ectoderm
Which direction does the neural plate lengthen?
Cranial to Caudal
How do the neural folds and neural grove form?
By the end of the third week, the lateral edges of the plate will become elevated. The resulting depression in the middle is called the neural groove.
How does the neural tube form and what is this a precursor to?
The neural folds will eventually fuse and this forms the tube. This is precursor to the CNS.
What cell population forms the PNS?
Neural crest
What are the two planes that embryonic folding occurs in?
Horizontal and Median
What folds are the result of the Horizontal plane?
Two lateral folds
What folds are the result of the Median plane?
Cranial and Caudal fold
How does the primitive gut tube form?
This is where the endoderm fuses. The endoderm will incorporate the dorsal yolk sac to create the primitive gut tube.
How does the vitelline duct form?
This is where the mid-gut forms a connection with the yolk sac and as folding increases, the connection will become narrower and form the vitelline duct.
How does the notochord form?
This is where mesenchyme cells will migrate to from the primitive node and they form the notochordal process. This grows cranially until it reaches the prechordal plate.
Which two membranes have the endoderm and ectoderm directly in contact?
Oropharyngeal (prechordal plate) and the Cloacal membrane.
What type of relationship does the notochord have with the ectoderm?
Inductive
Where is noggin and chordin released?
Notochord
What do chordin and noggin inactivate?
BMP4: this allows patterning of the neural tube
What induces the ectoderm to form the neural plate and what cells make up the neural plate?
The notochord induces the ectoderm to thicken and produce the neural plate. The cells are called neuroectoderm cells.
What are the two hinge point of the neural tube?
Median and Dorsolateral
Where does fusion of the neural tube begin?
Cervical region
What does the neural tube form when it get exposed to sonic hedgehog?
The floorplate. This will then make its own SHH and form motor neurons.
What are the signalling levels in the upper spine?
There is no dorso-lateral hinge points as they are inhibited by BMP2. There is a lot of SHH and this causes the inactivation of noggin. There is only the median hinge point.
What are the signalling levels in the lower spine?
SHH is reduced and this means that Noggin is activated. This inactivates BMP-2 and this allows Dorsolateral hinge points to form.
What are the two transmembrane proteins that SHH requires and what transcription factors are involved?
Transmembrane protien: smoothened and patched
Transcription factors: Gli family
How does the roof plate form?
BMPS from the ectoderm upregulate PAX-3 and PAX-7, allowing the roofplate to form. Since it is in the dorsal aspect, sensory neurones form.
What are some cardiovascular changes during pregnancy?
- cardiac output increases
- maternal heart rate increases
- stroke volume increases
- mild hypertrophy due to increase demand
- functional murmurs
Cardiac output may increase towards the end of pregnancy due to the uterine obstructing the inferior vena cava and reducing venous return.
What are some changes in the volume and composition of blood during pregnancy?
- plasma volume increases 50%
- haemoglobin increase 30%
Due to larger increase in plasma compared to RBC, dilutional anaemia is common. - there is an increase in fibrogen and clotting factors and this can give a risk to clotting factors
What are the changes in blood pressure during pregnancy?
Due to the decreased vascular resistance, blood pressure will decrease.
What are the changes in respiraoty during pregnancy?
- due to uterus obstruction, the total lung capacity and residual volume will decrease
- tidal volume will increase
- diaphragmatic breathing occurs because of he uterus increasing abdominal pressure
- progesterone will cause oedema in the respiraoty tissues and this may lead to nasal stuffiness and voice changes
What are the changes of renal function and body fluid during pregnancy?
Due to cardiac output increasing, renal blood flow will increase and this will decrease the amount of urea and creatinine in the blood.
The increased pressure on the inferior vena cava will and increased function of the kidney will increase urination.
What hormone causes oesophageal relaxation and may cause nausea?
Progesterone.
This may cause heart burn and belching.
What factors contribute to constipation during pregnancy?
Increased pressure, progesterone relaxing effects and increased water reabsorption.
Where is human chorionic gonadotropin secreted and what is the function?
This is secreted by syncytiotrophoblasts cells. This is a luteophilic hormone that prolongs the life of the corpus lutuem. The prolonging of this means that progesterone can be continually secreted and this prevent shedding of the endometrium.
Absence of luteal progestogen would cause a miscarriage.
Progestogen is then secreted by the placenta and when this occurs, hCG decreases rapidly.
hCG inhibits the secretion of FSH and LH and this suppressed ovulation.
What is Oestriol?
Oestriol is one of three oestrogens naturally produced by women. Normally, levels in the body are very low, but during pregnancy, it is made in much higher amounts by the placenta. Oestriol levels increase throughout pregnancy and are highest just before birth. It is an indicator of the health of the unborn fetus because the chemical from which it is made in the placenta, comes from another chemical which is first made in the baby’s adrenal glands and then gets altered in the liver of the baby before being finally converted to oestriol in the placenta. It causes growth of the uterus and increases its sensitivity to other pregnancy-related hormones, thus causing a gradual preparation for birth. Oestriol levels start to increase from week eight of pregnancy and scientists now think that labour begins when oestriol becomes the dominant hormone.
How is oestriol controlled?
Oestriol is made by the placenta from a chemical that comes from the fetus. The fetal adrenal glands first make a hormone called dehydroepiandrosterone sulphate (DHEAS). DHEAS is then transported to the fetal liver and made into 16a-hydroxy-DHEAS. The 16a-hydroxy-DHEAS is in turn transported to the placenta where it is then made into oestriol. For most of pregnancy, most of the oestriol made is bound to other chemicals thereby preventing the oestriol from exerting any biological effects.
What is Human Placental lactogen and what is the function?
This increases as levels of hGR decrease, around 8 weeks. It is secreted by syncytiotrophoblasts and it is mainly in maternal blood.
The principle action is to increase proliferation of breast tissue.
Why is there an increased amount of urination during the early stages of pregnancy?
Human chorionic gonadotrophin can be detected in the urine as early as 7-9 days after fertilisation and is used as an indicator of pregnancy in most over-the-counter pregnancy tests. It is partly responsible for the frequent urination often experienced by pregnant women during the first trimester. This is because rising levels of human chorionic gonadotrophin causes more blood to flow to the pelvic area and kidneys, which causes the kidneys to eliminate waste quicker than before pregnancy.
What affect does hPL have on insulin sensitivity?
This increases the sensitivity to insulin and this means that glucose may decrease.
What is the function of Relaxin?
This is produced by the corpus luteum and by the cytotrophoblast cells. Thus softens the cervs and relaxes the ligaments in preparation for delivery.
What function does progesterone have during he first early stages of pregnancy?
Increasing blood flow to the womb by stimulating the growth of existing blood vessels
Stimulating glands in the lining of the womb (the endometrium) to produce nutrients that sustain the early embryo
Stimulating the endometrium to grow and become thickened, producing the decidua, a unique organ that supports the attachment of the placenta and allowing implantation of the embryo
Helping to establish the placenta
How does the placenta make progesterone?
Converts mother’s cholesterol into progesterone. Production is stimulated by oestrogen.
What are the functions of progesterone during mid to late pregnancy?
Being important for correct fetal development
Preventing the muscles of the womb contracting until the onset of labour
Preventing lactation until after pregnancy
Strengthening the muscles of the pelvic wall in preparation for labour
Explain the process of making oestrogens
Oestrogen and in fact, progesterone production from the placenta is stimulated by oestrogen. Oestrogen is made and released by the corpus luteum of the ovaries and then later, the fetal-placental unit, where the fetal liver and adrenal glands produce the hormone oestriol (an oestrogen often used to determine fetal wellbeing in pregnancy), that is passed to the placenta where it is converted into other oestrogens
What are some functions of oestrogen?
Maintaining, controlling and stimulating the production of other pregnancy hormones
Needed for correct development of many fetal organs including the lungs, liver and kidneys
Stimulating the growth and correct function of the placenta
Promoting growth of maternal breast tissue (along with progesterone) and preparing the mother for lactation (breastfeeding)
What is the function of oxytocin during pregnancy?
Oxytocin levels rise at the onset of labour, causing regular contractions of the womb and abdominal muscles. Oxytocin-induced contractions become stronger and more frequentwithout the influence of progesterone and oestrogen, which at high levels prevent labour.
What is the function of Corticotrophin-releasing hormone, in relation to the immune system and late pregnancy?
in the first days of pregnancy, corticotrophin-releasing hormone suppresses the mother’s immune system, preventing the mother’s body from attacking the fetus. Later in pregnancy, it improves the blood flow between the placenta and fetus. In the last weeks of pregnancy corticotrophin-releasing hormone levels climb even higher – a rise which coincides with a major spike in cortisol levels. The rise in corticotrophin-releasing hormone and cortisol may help the fetal organs mature just before labour begins, and influence the timing of birth, through production of a ‘late-term cortisol surge’.
When does the heart start to pump?
Week four
When does the heart conduction system form?
Week 6
When does the physiological umbilical hernia form?
Week 5: out
Week 10: back in
When do the major and minor calyces appear?
Week 6
What week shows the first sign of sex differentiation?
Week 6
Why is folic acid essential during pregnancy?
RNA and DNA synthesis
Protein synthesis
Red blood cell formation
Folate is needed to carry one carbon group for methylation and nucleic acid synthesis
Why is folate deficiency a problem with neural tube formation?
During folate formation, there is a rapid cell dividing and this requires a lot of DNA synthesis. Therefore, it there is not enough, then DNA synthesis can not meet the demand.
What is anencephaly?
This is where the head of the neural tube fails to close. The brain initially protrudes through a defect in a cranial vault and then becomes damaged. There is a part of the brain missing.
What is Encephalocele?
Encephalocele, sometimes known as cranium bifidum, is a neural tube defect characterized by sac-like protrusions of the brain and the membranes that cover it through openings in the skull.
What is hydrocephalus?
Accumulation of CSF
What is spina bifida occulta?
This is mild and very common. Many people have it but don’t become aware of it until a back x-ray. The spinal cord and the meninges remain undamaged. The skin may have more hair, birthmark or dimple.
What is spina bifida cystica and what are the two types?
Spina bifida cystica occurs when the lining (membranes) of the spinal cord and sometimes the spinal cord push out through the defect in the spine. The two main types of spina bifida cystica are called meningocele and myelomeningocele:
What is Meningocele spina bifida?
Spina bifida meningocele is the rarest type of spina bifida. The protective membranes (the meninges) surrounding the spinal cord are pushed out between openings in the vertebrae. The meningocele is sometimes covered by a layer of skin. There are no spinal cord nerves in the protruding sac. The membranes can usually be removed by surgery.
What is Myelomeningocele spina bifida?
This is the most serious type of spina bifida. About one pregnancy in every 1,000 pregnancies is affected in the UK. The spinal column remains open along the bones making up the spine. The membranes and spinal cord push out to make a sac on the baby’s back. This sometimes leaves the nervous system at risk of infections that may be life-threatening.
In most cases of myelomeningocele, surgery can be carried out to close the defect. However, damage to the nervous system will usually already have taken place. The nerve damage can cause a range of symptoms, including weakness (paralysis) of the legs and loss of feeling in the skin of the legs. There may also be problems with passing wee (urine) and poo (faeces, stools or motions).
What are the causes of Neural tube defects?
- lack of folic acid
- gene-environmental interaction: methotrexate, obesity, radiation
- family history
- medication: valproate, carbamazepine
What is the difference between open and closed NTDs?
Open: this occurs when the brain and/or spinal cord is exposed through a defect in the skull of vertebrae
Closed: this is where the spinal defect is covered by skin
How is a neural tube defect diagnosed?
This is diagnosed with alpha-fetoprotein (AFP) and acetylcholinesterase.
AFP, a circulating fetal protein produced by liver, peaks at 12-14 weeks and then declines. AFP leaks into the amniotic fluids trough exposed capillaries of NTD. This causes high amounts of AFP in the blood and fluid.
Acetylcholinesterase is also able to lead into the fluid from exposed neural tissue.
When do facial features develop?
Weeks 6-9
What are thee pitfalls of studying screening effects?
- healthy volunteer bias
- lead-time bias
- length-time bias
What enzyme follows DNA polymerase?
DNA mismatch repair complex
What is mutated in nonpolyposis colon cancer?
DNA mismatch repair complex
What type of mutation does UV radiation cause?
Thymidine dimerization
What is the function of nucleotide excision repair?
Recognizes DNA damage
When does anterior neuropore close?
Day 25
When does posterior neuropore close?
Day 27
What is the function of folate in metabolic pathways?
Maintenance of red blood cells
What defect is associated with the failure of the anterior neural tube?
Anencephaly
When is amniocentesis carried out?
14-16 weeks
When is chorionic villi sampling carried out?
10-14 weeks
When is the first trimester combined test carried out?
11-14 weeks
What is the risk of miscarriage in amniocentesis?
1%
What is the risk of miscarriage in chorionic villi sampling?
2%
What does chorionic villi sampling and amniocentesis check for?
Karyotype: to see it there is trisomy 21 or Robertsonain translocation
What are the levels of PAPP-A, hCG, oestradiol, Inhibin A, AFP in Down syndrome?
PAPPA: decreases hCG: increases Inhibin A: increases AFP: decreases Oestradiol: decreases
