1
Q
What is the EPOR model (4 phases of human sexual response)?
A
- EXCITEMENT: sexual arousal
- PLATEAU: intensification of arousal
- ORGASM: involuntary muscular contractions in both sexes
- RESOLUTION: detumescence & re-arousal is impossible (may not be true of women)
2
Q
What phases in women cycle are varied/fixed in time?
A
- Luteal phase FIXED at approx 14days
- Follicular phase VARIES
- Menstrual phase VARIES
3
Q
How long is sperm viable for?
A
24-72hrs
4
Q
How long is oocytes viable for?
A
12-24hrs
5
Q
When must coitus occur for fertilisation to occur?
A
No more than 3 days before ovulation & no more than 1 day after
6
Q
What is coitus?
A
Sexual intercourse
7
Q
How long are sperm capable of fertilising an egg?
A
4-6days
8
Q
How long does an ovulated egg remain viable for?
A
Approx 24-48hrs
9
Q
Describe the trimesters of pregnancy?
A
- 1ST (weeks 1-12): most miscarriages occur
- 2ND (weeks 13-28): at 24weeks 50% survival rate for early prematurity
- 3RD (weeks 29-40): parturition at ~40weeks from LMP
10
Q
How likely are women to conceive (study of women <35yrs in china & europe)?
A
- 50% pregnant after 2 cycles
- 85% pregnant after 6 months
- 1/2 remaining were pregnant after 1yr
- ~5% subfertile
11
Q
What % of pregnancies miscarry?
A
10-15%
12
Q
What is a spontaneous abortion?
A
Pre-implantation & post-implantation failure occurring frequently
13
Q
What % of unprotected intercourse will result in blastocyst stage?
A
20%
14
Q
What % of blastocysts fail to implant?
A
8-20%
15
Q
What % of clinically detected pregnancies will fail in the 1st 12 weeks?
A
15-20%
16
Q
What is the cause of abnormalities?
A
Chromosomal caused by non-disjunction (aneuploidy), sperm DNA shows high rates of mutation because they lack DNA repair system
17
Q
What are the 3 stages of the embryonic period (8weeks)?
A
- Preimplantation embryo
- Implantation
- Differentiation & development of organ systems
18
Q
What are the 2 stages of the foetal period (8-40weeks)?
A
- Differentiation continues
2. Growth
19
Q
What 2 things happen at ovulation?
A
- Egg extruded onto surface of ovary
2. Smooth muscle of fimbriae cause them to pass over ovary while cilia beat in waves towards interior of duct
20
Q
What is the purpose of Cumulus cells?
A
- Aid transport from surface of the ovary
- Sticky cells cling to claimed surface of fimbriae
- Transported by ciliary current (& perhaps peristalsis) to ampulla
21
Q
Describe intercourse & sperm transport?
A
- Ejaculation deposits semen into vagina
- Passage into cervical mucus dependent on oestrogen-induced changes in mucus consistency
- Movement through uterus & fallopian tubes via sperm’s own propulsions & uterine contractions
22
Q
Why do several 100 million to 100-200 sperm die when travelling from vagina to fallopian tubes?
A
- Vaginal environment is acidic
- Length & energy requirements of trip are large
23
Q
What does capacitation of sperm cause?
A
- Change from wavelike beats of tail to whip-like action to propel sperm
- Sperm’s plasma membrane altered so its capable of fusing with surface membrane of egg (acrosome reaction)
24
Q
How does capacitation destabilise sperm’s surface membrane to enhance fusion with oocyte?
A
- Increase in Ca2+ permeability (rise in intracellular Ca2+)
- Removal of membrane proteins (glycoproteins)
- Change in surface charge
- Depletion of cholesterol
25
When does fertilisation usually occur?
Few hrs after ovulation & within 24-48hrs of ovulation
26
What are the 8 processes which occur in fertilisation?
1. Sperm cell weaves past follicular cells & binds to zone pellucida
2. Rise in [Ca2+]i triggers exocytosis of acrosome
3. Hydrolytic enzymes released, dissolving zona pellucida
4. Head of sperm lying sideways, microvilli on oocyte surround sperm head, membranes fuse
5. Rise [Ca2]i occyte triggers cortical reaction
6. Rise [Ca2+]i ooctye induces completion of oocytes 2nd meiotic division & formation of 2nd polar body
7. Sperm head enlarges to become male pronucleus
8. Male & female pronuclei fuse
27
Describe the Acrosome reaction which occurs during the 2nd step of fertilisation?
- Fusion of acrosome plasma membranes
- Releases contents of acrosome (hydrolytic enzymes in acrosomal cap)
- Causes more Ca2+ entry
- Sperm digests a path through zona pellucida (proteolytic enzymes)
28
What induces the acrosome reaction?
Sperm head contacting the zona pellucida & binding to glycoproteins ZP2 & ZP3
29
Describe the Cortical reaction which occurs during the 5th step of fertilisation?
- Exocytosis of granules that previously lay immediately beneath the plasma membrane
- Enzymes released lead to changes in zona pellucida proteins = harden, preventing entry of other sperm
30
Describe the male & female pronuclei fusion which occurs during the 8th step of fertilisation?
- Sperm contributes its nuclear material & centrioles
- All other organelles are present in oocyte cytoplasm
- Mitochondrial DNA inherited exclusively via maternal route
31
What happens 2-4 days after LH peak?
Cell division to ~32 cells in fallopian tube
32
What happens 5 days after LH peak?
Blastocyst enters uterine cavity
33
What happens 6-7 days after LH peak?
Implantation at the uterus
34
What happens 9-10 days after LH peak?
Human chorionic gonadotropin (hCG) from implanted blastocyst (trophoblast cells) rescues corpus luteum, located at trophoblast --> maternal ovary
35
How is conceptus "held" in fallopian tube?
Oestrogen maintains contraction of smooth muscle near where fallopian tube enters wall of uterus
36
Describe the process of cell division to ~32 cells?
- Conceptus undergoes number of mitotic cell divisions ie. cleavage & morula formed
- Unusual as no cell growth occurs before each division, therefore conceptus reaching uterus is same size as original fertilised egg
- Cells are totipotent
37
What are totipotent cells?
- Can form all the cell types in a body, plus the extraembryonic, or placental, cells.
- Embryonic cells within the 1st couple of cell divisions after fertilisation are the only cells that are totipotent
38
What are pluripotent cells?
Can give rise to all of the cell types that make up the body (embryonic stem cells)
39
What are multipotent cells?
Can develop into more than 1 cell type, but are more limited than pluripotent cells (adult stem cells & cord blood stem cells)
40
Why are blastocyst removed for screening?
They are pluripotent so a cell can be removed for testing without damage to the embryo
41
Describe how the conceptus/blastocyst enters the uterine cavity?
- Plasma progesterone rise 3-4days after fertilisation, smooth muscle relax
- 4-5days after fertilisation, cavities develop
- ~3days, conceptus/blastocyst lies free in uterine cavity supported by uterine secretions
42
What does trophoblast of the blastocyst give rise to?
Placenta
43
What does inner cell mass of the blastocyst give rise to?
Form embryo
44
What happens to blastocyst at day 6?
Attaches to endometrium adjacent to inner cell mass (embryonic pole)
45
What does the trophoblast differentiate into?
- Inner cytotrophoblast
| - Outer syncytiotrophoblast (loses cell boundaries)
46
Where are the different sites which metabolism occurs?
- Gut lumen
- Gut wall
- Plasma
- Lungs
- Kidneys
- Nerves
- Liver
47
What are the 2 phases of metabolism which mainly occur in the liver?
- PHASE I: oxidation, reduction or hydrolysis. Reveal/introduce reactive group "functionalisation", produces more reactive
- PHASE II: synthetic, conjugative reactions. Hydrophilic, inactive compounds generated
48
What happens to hydrophilic drug molecules during metabolism?
Hydrophilic molecules --> kidney --> urine
49
What happens to hydrophobic drug molecules during metabolism?
Hydrophobic molecules --> hydrophilic metabolite --> kidney --> urine
OR...
Hydrophobic molecules --> conjugate --> bile --> intestines --> faeces
50
What 6 reactions occur during Phase I (functionalisation) metabolism?
- Oxidation
- Reduction
- Hydrolysis
- Hydration
- Dethioacetylation
- Isomerisation
51
What 8 reactions occur during Phase II (conjugative) metabolism?
- Glucuronidation/glucosidation
- Sulfation
- Methylation
- Acetylation
- Amino acid conjugation
- Glutathione conjugation
- Fatty acid conjugation
- Condensation
52
Give examples of oxidation reactions in Phase I metabolism?
- Mixed-function oxidase system (cytochrome P450)
- Alcohol dehydrogenase
- Xanthine oxidase
53
Give examples of reduction reactions in Phase I metabolism?
- Ketone reduction
| - Anaerobic cytochrome P450 metabolism
54
Give examples of Hydrolysis reactions in Phase I metabolism?
- Ester hydrolysis (ie. cholinesterases)
| - Amide hydrolysis
55
Describe Mixed-function oxidase systems (CYP450s)?
- Microsomal (ER) enzymes
- Consists of cytochrome P450, NAPDH-CYP450 reductase, lipid
- Requires molecular oxygen, NADPH
56
What does Phase II metabolism usually produce?
Detoxified, water-soluble, easily secreted products suitable for excretion in bile or urine
57
What are the 3 causes of variation in drug metabolism?
1. Many enzymes capable of metabolising drugs
2. Potential for competition & saturation
3. Issues of variation/induction/inhibition
58
In what 2 ways are drugs eliminated?
1. Unchanged
| 2. As metabolites
59
In general, hydrophilic drugs are eliminated _____ than lipophilic drugs?
MORE
60
Give examples of the possible sources of excretion for drugs?
- Urine
- Faeces
- Breath
- Milk
- Saliva
- Perspiration
- Hair
- Bile
61
What is the most important organ involve in elimination of drugs & their metabolites?
Kidneys
62
What 3 things transfer drugs from plasma to bile?
1. Organic cation transporters (OCTs)
2. Organic anion transporters (OATs)
3. P-glycoproteins (P-GP)
63
What can happen to the drug concentrated in bile once delivered to the intestines?
- Hydrophilic drug conjugates (ie. glucuronides)
- Hydrolysis of conjugate can occur
- Reabsorption of liberated drug
- Enterohepatic circulation
64
Describe the Enterohepatic circulation?
Conjugate in liver --> conjugate in bile --> conjugate in intestines (excretion in feces) --> drug in intestine --> drug in blood (renal excretion)
65
Describe glomerular filtration of drug?
- Filters drugs below 20kDa mol. weight
| - Not filtered if drug bound to plasma albumin
66
Describe Tubular secretion of drug?
- OATs & OCTs
- OATs transport against electrochemical gradient
- Cleared even if bunch to plasma albumin
67
How much of the drug is reabsorbed if the renal tubule is freely permeable?
99%
68
What happens to lipophilic & polar drugs in the renal tubule?
- Lipophilic excreted poorly
| - Polar remain in lumen
69
What causes weak acids to be more rapidly excreted?
Alkaline urine
| oposite for weak bases
70
Describe Zero order kinetics?
- Few drugs
- Rate of metabolism is constant
- Does NOT vary with amount of drug present
- Enzyme saturation (alcohol dehydrogenase)
71
Describe 1st order kinetics?
- Most drugs
- Constant fraction metabolised/unit time
- Increases proportionately to drug
- More drug, faster metabolism
72
Describe the metabolism of Salicylic acid (hydrolysis of aspirin)?
- Non-linear kinetics
| - High doses saturate
73
What is the Apparent volume of distribution (Vd)?
Total amount of drug in body/ Blood plasma conc. of drug
| L or L/kg
74
What is the clearance of a drug (CL)?
Sum of all routes of elimination (ie. metabolism + excretion)
(L/h)
75
Describe the relationship between t1/2 (half-life), Vd & CL of a drug?
t1/2 depends on Vd & inversely on CL of drug from the body
76
What are the 4 different factors that can affect metabolism?
1. Age: decreases as age increases
2. Genetic variation: wide range of CYP phenotypes, race
3. Disease: need proper liver function, adequate essential amino acid, severe burns
4. Other Medication: induction of metabolic enzymes, inhibition of metabolic enzymes
77
What 3 phases develops an anatomical link between the mother & foetus?
1. Invasion
2. Decidualisation
3. Placentation
78
What makes the maternal portion of placenta?
Endomertium underlying the chorion
79
How is the endometrium around villi changed?
Changed by enzymes & paracrine agents so each villi is surrounded by a pool/sinus of maternal blood
80
Describe the maternal blood supplying the placenta?
- Enters placental sinuses/pools via uterine artery
- Flows through sinuses
- Exits via uterine veins
81
Describe the foetus blood supplying the placenta?
Flows into capillaries of choronic villi via umbilical arteries & back to foetus via umbilical vein
82
What connects the foetus to placenta?
Umbilical cord
83
What happens to the blastocyst at day 6/7 (end of week 1)?
- Leaves zona pelucida & is bathed by uterine secretions for 2 days
- Progesterone prepares supportive uterine environment increasing glandular tissue
- Oestrodiol is required to release glandular secretion
84
Describe the Attachment & Implantation of Blastocyst which occurs at the end of week 1?
- Limited time window
- Syncytiotrophoblast cells "flow" into endometrium
- Causing oedema, glycogen synthesis & increased vascularisation (decidualisation)
- Pregnant endometrium is now termed the decidua
85
Describe the implantation which occurs at day 13 (time woman expects her next period)?
- Syncytiotrophoblast erode through the walls of maternal capillaries, bleed into the spaces (primitive placental circulation).
- Nutrition depends on uterine secretion & tissues
- Breakthrough bleeding may occur
86
What resides in the core of the villus?
Fetal capillary loop, dilated at the tip (slow flow rate)
87
What eventually happens to the chorionic villi?
Become localised at embryonic pole & present a huge surface area for exchange of O2, nutrients & waste products
88
When does the maternal side of the placental circulation begin to function?
10-12 weeks
89
What separates maternal & fetal circulations?
Placental membrane, no mixing!
90
What are syncytiotrophoblasts bathed in?
Maternal blood
91
How thick should the endometrium be for successful implantation?
Atleast 8mm
92
How is the trophoblastic lacunae formed?
- Syncytiotrophoblast forms a network of interconnected cords invading endometrium & eroding the maternal capillaries
- Expanded uterine spiral arteries connect with trophoblastic lacunae
93
What 2 things make up the primary villus?
Core of cytotrophoblast covered by multinucleated syncytiotrophoblast
94
What 3 things make up the secondary villus?
1. Inner core of extra embryonic mesoderm
2. Middle cytotrophoblast layer
3. Outer syncytiotrophoblast layer
95
How long does LH support the steroid secretion of the corpus luteum?
10-12days
96
What is the function of hCG (human chorionic gonadotropin)?
Mimics action of LH & supports steroid synthesis (progesterone) of corpus luteum & therefore prevent menstruation & any further follicular development
97
What secretes hCG?
Syncytiotrophoblasts soon after implantation (peaks ~8-10 weeks)
98
When can hCG be detected in maternal blood by immunoassay?
From day 6-7
99
When can commercial kits detect hCG in urine?
After ~14days
100
What are the placental functions in the 1st 3 months?
- 1st month: villus formaiton
- 2nd month: increasing surface area & circulation
- 3rd month: growing, becoming increasingly efficient
101
What are the 4 "organ-like" functions of the placenta?
1. "Gut": supplying nutrients
2. "Lung": exchanging O2 & CO2
3. "Kidney": regulates fluid volumes & disposing of waste metabolites
4. "Endocrine": synthesises steroids & proteins that affect maternal & foetal metabolism
102
Why must be have progesterone for the maintenance of pregnancy?
- Suppresses follicular growth & ovulation
- Suppresses immune response
- Maintenance of endometrium
103
When does the placenta secrete all steroid hormones required for pregnancy?
4-5weeks
104
what is the substrate for progesterone production?
Cholesterol from the maternal circulation
105
What is the main oestrogen in pregnancy?
Oestriol
106
What are the 4 functions of oestrogen in pregnancy?
1. Stimulates growth of uterine myometrium
2. Stimulates growth of ductal tissue of breast
3. Along with relaxin, relaxes & softens maternal pelvic ligaments & symphysis pubis allowing expansion of uterus
4. Stimulate LDL cholesterol uptake & P450 enzyme activity
107
What does oestrogen levels measure?
Foetal well being & placental function
108
Describe the nutrient exchange across the placenta?
- Rapid, increases as pregnancy advances
- H20 & electrolytes diffuse freely
- Glucose via facilitated diffusion
- Amino acids actively transported
- Lipids cross as free fatty acids
- Vitamins
109
What can be stored for postnatal requirements?
Glycogen in liver
110
Babies from what type of mothers are typically heavier than normal range?
Diabetic mothers
111
Describe gas exchange across the placenta?
- Simple diffusion of gases close to efficiency of lungs
- Concentration gradients influenced by blood flow rates
- Quantity of O2 reaching foetus flow limited
- End of pregnancy exchange capacity decreases & placenta less able to meet demands
112
What has a greater affinity for O2- adult or fetal haemoglobin?
Fetal haemoglobin
113
Where are 95-97% of ectopic pregnancies found?
Ampulla/isthmus of the tube
114
What can rupture of the fallopian tube cause?
Blood loss that may be lifer threatening to mother & fatal for embryo
115
What can symptoms of ectopic pregnancy be confused with?
Appendicitis
116
What is the definition of "Genetic counselling" according to the Task Force of National Society of Genetic Counsellors (2006)?
- Process of helping people understand & adapt to the medical, psychological & familial implications of genetic contributions to disease
- Families get a "crash course" in medicine"
117
What 3 things does the process of Genetic counselling integrate?
1. Interpretation of family & medical histories to assess chance of disease occurrence/recurrence
2. Eduction of inheritance, testing, management, prevention, resources & research
3. Promote informed choices & adaptation to the risk or condition
118
Describe the newborn screening programme for Cystic fibrosis?
- Heel-prick immunoreactive trysinogen (IRT) level = stressed pancreas
- Raised IRT test using CF mutation kit
119
When is cystic fibrosis suspected in newborn testing?
Raised IRT & 1 pathogenic mutation found
120
When is cystic fibrosis confirmed in newborn testing?
2 pathogenic mutations found
121
Describe the "mild" mutation R117H?
- 2nd mutation in 1.85% of Scottish CF patients
- 9% of CF mutations identified on postnatal screen
- Majority do NOT present with CF in childhood
- Effect varies to Intro 8 splice site efficiency
122
What CFTR Intron 8 variant is the most common in population?
7T
123
Describe the 5T CFTR Intron 8 variant?
Poor splicing resulting in exon 9 skipping, its not producing much full length protein (10% of normal CRTR)
124
What new drug artificially opens the chloride channel in G551D mutation?
Ivacaftor
125
What is R117H associated with?
Male Infertility
126
What is the risk of Spinal Muscular Atropy if a couple has already had an affected child?
1 in 4 recurrence risk
127
Describe cleavage stage biopsy?
- Need lots of embryos
- Remove 1 cell day 5
- Whole genome amplification
128
Why not look directly for mutation?
- Single cell, very low copy number DNA
- Problem with contamination (false +)
- Allele drop out (false - from failure to amplify)
- Expensive
129
What tests would be done for a mother who has had recurrent previous miscarriages?
Ultrasound at week 8 (earlier than normal, usually bad news if abnormalities detected at 13 weeks)
130
What is Trisomy 13 also known as?
Patau syndrome (associated with renal defects)
131
What is the pre-symptomatic testing protocol?
- Full information on test & limitations (non-directive)
- Opportunity for facilitated decision making
- Meet 2-3x before test to ensure understanding
132
What are the 3 issues with pre-symptomatic testing?
1. Insurance company cannot use results to increase premium
2. Employment
3. Relationships
133
What are the 4 key points for genetic counselling?
1. Good family history (atleast 3 generations)
2. Genetic diseases can be associated with different phenotypes
3. Diagnosis in 1 family member will often have implications for other family members
4. Lab tests should be interpreted in light of clinical features
134
What is Cascade testing?
- Rest of extended family may be worried, can test them all.
- Not as necessary for autosomal recessive disorders, unless very worried
- Other sibling may be a carrier
135
What should you remember regarding sequencing?
Reveals the sequence of total DNA, so both chromosomes are mixed together not each chromosome separately
136
What is Haplotyping?
- Group of genes within an organism that was inherited together from a single parent
- Look at inheritance of chromosome markers around site of disease associated mutation
137
What is the mutation for early onset of Alzheimers disease?
- Substitution mutation in exon 7 of PSEN-1 gene changing codon 214 from CAC to TAC
- Replaces histidine with tyrosine in the PSEN-1 protein (missense)
138
When is the fundus of the uterus palpable abdominally?
From 13 weeks gestation
139
Where does the uterus reach at term?
Xyphoid process (thorax widens as ribs flare to accommodate organs)
140
What anatomical changes does the mother experience during pregnancy?
- Changes centre of gravity causing accentuated lumbar lordosis (backache)
- Relaxin causes softening of ligaments (sacroiliac & symphysis pubis pain)
141
Describe the average weight gain a pregnant woman has?
- ~7-14kg total
- 6kg uterus, foetus & breast
- 3kg fat reserves for lactation
- Remainder is fluid
142
Why are pregnant woman prone to varicose veins & ankle oedema?
Pressure on IVC esp when lying down will impede venous return fro lower limbs & may impair function of valves
143
Describe physiological anaemia of pregnancy?
- Haematopoiesis is increased (up 30%)
| - Plasma volume increase (up 50%) means haematocrit, red cell count & haemoglobin concentration decrease
144
What are the other circulatory adaptations (blood volume & composition) during pregnancy?
- Small increase in WBC
- Unchanged platelet count, but more reactive
- Increase in clotting factors with thromboembolism risk
145
Describe the uteroplacental circulation?
High volume, low resistance flow as uterine spiral arteries & arterioles lose capacity to vasoconstrict
146
What do pregnancy hormones do to the woman sensitivity to pressor agents?
Reduce sensitivity (ie. angiotensin), hence peripheral vasodilatation (heat-intolerance)
147
What does reduced TPR trigger in pregnancy?
Renin-angiotensin-aldosterone system increasing blood volume
148
What additional factors favour vasodilation, maintaining normal (low) blood pressure?
- Oestrogen increases vascular endothelial growth factor (VEGF) & nitric oxide (NO)
- Endothelial cells release prostacyclin (prostaglandin I2 or PGI2)
149
What happens to the woman's cardiac output (CO) during pregnancy?
- Increases by 30-50% between weeks 6-28 (~6L)
| - In late pregnancy, CO sensitive to posture (hypotension/fainting when lying flat)
150
What happens to Heart Rate (HR) & Stroke Volume (SV) during pregnancy?
- HR: increases 70/min to 80-90/min
| - SV: increases ~10%
151
When does the woman's Cardiac Output (CO) return back to pre-pregnancy condition?
6 weeks post-partum
152
How is the pregnant woman's blood pressure (BP) measured?
Semi-recumbent using Korotkoff phase 5 for diastolic
153
Describe a pregnant woman's blood pressure?
- Although CO increases, BP normally falls in 2nd trimester
- Systolic falls ~5-10mmHg
- Diastolic falls ~10-15mmHg
154
Describe Pre-eclampsia?
- Placental problem involving increase in BP, proteinuria & oedema
- May involve failure of 2nd wave of trophoblast invasion that normally impairs capacity of material spiral arterioles to constrict (12-16weeks)
155
How common is pre-elcampsia?
~2-8% of pregnancies, more common in 1st pregnancy
156
What 3 things does increased vascular resistance in placenta during pre-elclampsia cause?
- Decrease blood to placenta
- Hypertension in mother
- Renal arteriolar endothelial damage causes oedema, glomerular damage & proteinuria (acute atherosis)
157
Describe Eclampsia?
- Potentially fatal, Extreme hypertension (ie. 180/120)
- Increased intracranial pressure, seizures, coma
- Significant risk of cerebral haemorrhage
158
What % of maternal mortality does eclampsia cause?
~8-36%
159
What are 4 interventions for eclampsia?
1. Magnesium sulphate
2. Antihypertensives
3. Rapid delivery
4. Careful fluid balance
160
What happens to the woman's respiratory system during pregnancy?
- Progesterone increases sensitivity of central CO2 receptors
- Deep ventilation
- Increase tidal vol by ~40%
- Rate unchanged
161
What happens to the woman's renal system during pregnancy?
- Increased glomerular filtration rate (GFR), due to increase CO
- Decreased plasma urea, creatinine & uric acid
- Ureters dilated, predisposing to infection
162
What is the most useful renal marker in pregnancy & why?
Uric acid as it rises before creatinine in response to renal impairment (ie. pre-eclampsia)
163
Why do pregnant women urinate frequently & urgently?
Bladder is compressed
164
What happens to the total body water (TBW) in pregnant women?
- Increases by ~6-8L
| - ECF increases by ~3L, split between plasma & interstitial fluid (ISF)
165
What happens to the osmolality in pregnant women?
- Falls by ~10mOsm/kg
| - Decreased urea & creatinine
166
What 3 GI system problems do pregnant woman commonly suffer with & why?
1. Morning sickness esp 12-14weeks: parallels HCG levels
2. Constipation: pressure on rectum & lower colon, decreased motility (progestognenic effect)
3. Gastric acid reflux, heartburn: relaxation of lower oesophageal sphincter, pressure of uterus, worse lying down, aspiration risk
167
How much should a woman's daily calorie intake increase when pregnant?
~15%, so 200-300kcal/day extra
168
Describe the physiological changes that occur in early pregnancy?
- ~3kg fat laid down for energy source in final trimester when growth is rapid
- Maternal tissues more sensitive to insulin
- increased protein synthesis
169
When does the growth of foetus peak?
30-36 weeks
170
Describe the physiological changes that occur in later pregnancy?
- Relative insulin resistance, predisposing to "high-normal" glucose
- Increase lipolysis
- Increase circulating triglycerides stored in mammary tissue
- Increased requirement for protein
171
What were the findings for Gestational weight gain (GWG)?
- Median 13.7kg
| - Different variations can all lead to a healthy outcome, weight gain doesn't matter
172
Describe gestational diabetes?
- Spectrum from normal to "impaired glucose tolerance" to actual diabetes
- Predictor of future type 2 diabetes
- Associated with foetal macrosomia (increase insulin resistance, high glucose)
173
What are the 3 risk factors for gestational diabetes?
1. Race
2. Obesity
3. Family history
174
What are the vitamin requirements for a pregnant woman?
- Folic acid needed for neural tube fusion
- Vegetarians may need increase B12 intake
- High levels of vit A may lead to foetal abnormalities
- Vit D supplementation
175
What are the mineral requirements for a pregnant woman?
- Calcium (calcification of skeleton)
- Maternal gut absorption increases (vit D3)
- Urinary loss decrease (parathyroid hormone)
- Increase in release of calcium from bone
- Active transport across placenta
176
Why do pregnant woman need Zinc?
- Important in many metabolic processes
- Protein synthesis
- Nucleic acid synthesis
- Synthesis/activity of insulin
- Increased dietary need, esp Vegans
177
When would pregnant women supplement Iron?
- If dietary iron low (maternal iron deficiency)
| - NOT when normal iron stores as it may increase oxidative stress
178
What are the endocrine secretions from the placenta during pregnancy?
- hCG: role in maintaining pregnancy
| - Other placental proteins & steroids
179
What are the endocrine secretions from the mother during pregnancy?
- Increased growth hormone
- Decrease FSH & LH
- Increased prolactin
- Increased parathyroid hormone
- Pituitary increases size
- Thyroid increases size due to hCG
180
What are the physiological post-natal changes that the woman's body undergoes?
- Uterine involution/shrink by 6 weeks
- Amenorrhoea if breast feeding
- Coagulation system changes reversed by longer than week 6
- Glucose tolerance normalises very rapidly
181
What can be the cause of 1. small babies 2. big babies?
1. Small: pre-eclampsia
| 2. Big: gestational diabetes
182
What is the Estimated Date of Delivery (EDD)?
- 40 weeks/ 280 days from the 1st day of last menstrual period (LMP)
- Actual fetal age will be 14 days less than EDD
183
What is delivery "at term"?
Between 37-42 completed weeks
184
What is delivery "pre-term"?
Before 37 completed weeks
185
What is delivery "post-term"?
Beyond 42 weeks
186
How do you estimate gestational age in 1st trimester?
- Gestation sac volume for very early gestation
| - Crown-rump length
187
How do you estimate gestational age in 2nd trimester?
- Head circumference
- Biparietal diameter
- Abdominal circumference
- Femur length
188
What is ultrasound biometry for in late pregnancy?
Growth not gestational age
189
What 3 things maintain the pregnant state?
1. Uterine quiescence: gap junction down regulated, oxytocin receptors down regulated, relaxin
2. Anatomical arrangement of the cervix: collagen fibres over smooth muscle, glycosaminoglycan
3. Amnion & chorion membranes are intact: low prostaglandin biosynthesis
190
How is labour initiated?
- Increased oestrogen encouraging uterine contractions
- Increased PG
- Increased cytosol-free calcium needed for muscular contraction
- Oxytocin
191
Describe cervical ripening during initiation of labour?
- Prostaglandin biosynthesis increases
- Increasing water content of glycosaminoglycan matrix
- Myometrial activity results "effacement" & thinning of cervix
- Relaxin upregulates matrix metalloproteinases
192
Describe uterine contractions during initiation of labour?
- Initially un co-ordinated, non painful "Braxton Hicks"
| - Progressively regular, frequent, co-ordinated & painful
193
What are the 4 stages of cervical effacement & dilation?
1. Not effaced, no dilation
2. Fully effaced, 1cm dilated
3. 5cm dilation
4. Fully dilated at 10cm
194
How long does labour take on average for Primiparous & Multiparous?
- Primiparous: 14hrs
| - Multiparous: 8hrs
195
Describe the 1st stage of labour?
- "Latent phase": painful contractions 5-10min intervals, cervical ripening & effacement, slowing dilating 3-4cm
- Active phase: cervix dilated 0.5-1cm/hr, increase in frequency & strength of contractions, cervical dilatation, descent of presenting part, membrane rupture
196
Describe the 2nd stage of labour?
- Cervix fully dilated (10cm)
- Contractions stronger 2-5mins
- Presenting part descends
- Urge to bear down
- "Ferguson reflex" of perineal stretching
- Deliver
- ~1hr long
197
Describe the 3rd stage of labour?
- Expulsion of placenta & membranes
- Separation due to forceful uterine contraction, reduces size of placental bed which reduces bleeding
- ~5mins
198
What are 2 ways of managing the 3rd stage of labour?
1. Expectantly (traditional or physiological)
| 2. Actively: oxytocic drugs (ergotamine), coupled with physically pulling umbilical cord
199
What are 5 factors influencing uterine contractions?
1. Prostagladins
2. Oxytocin
3. Relaxin
4. Stretch response
5. Positive feedback
200
Describe what prostaglandins (PGF2α & PGE2) do?
- Paracrines released from uterine decidual cells
- Stimulate uterine contractions
- Soften, thin & dilate cervix
- Potentiate contractions induced by oxytocin
- Increase gap junction numbers
201
Describe what oxytocin (posterior pituitary hormone) does?
- Triggers phospholipase C cascade & release of intracellular Ca2+ from smooth muscle SR (receptors on smooth muscle cells)
- Stimualtes PGF2α production
- Constricts uterine blood vessels at site of placenta
202
What does fetal oxytocin moving to maternal circulation do?
Onset of labour
203
What does maternal oxytocin do?
Released in bursts as a consequence of dilation of the cervix (Ferguson reflex)
204
What produces relaxin?
- Corpus luteum
- Placenta
- Decidua
205
What does relaxin do?
- Uterine quiescence
- Softens & helps cervix dilate during labour
- Affects collagen metabolism & soften ligaments
206
What are pregnant woman vulnerable to?
Ligamentous strain of relaxin
207
Describe the positive feedback influencing uterine contractions?
- Contraction stimulate prostaglandin release --> increases contraction intensity
- Contractions stretch cervix --> oxytocin release & stimulates further contractions
208
Describe engagement of the fetal head during labour & delivery?
- 2-4 weeks prior to delivery in primiparous
- May not happen in multiparous
- Presenting part descends into pelvis
209
What are the 4 stages of fetal delivery?
1. Engagement & flexion of head
2. Internal rotation
3. Delivery by extension of head, nose scrapes blanket
4. Delivery of shoulders
210
Describe the "lie" delivery presentation?
- Longitudinal (spines of mother & baby parallel)
| - Transverse would be abnormal more common in preterm & multiple pregnancies
211
Describe the "attitude" delivery presentation?
- Baby normally lies in "fetal" position (head tucked into chest)
- Crown of head/verte presents 1st (neck extended would be abnormal)
212
What % of delivery presentations are cephalic, breech, shoulder?
- Cephalic 97%
- Breech is buttock 1st 3%
- Shoulder 1%
213
What is External cephalic version (ECV)?
Manipulation of foetus through abdomen from breech to cephalic presentation from 36 weeks nulliparous or 37 weeks multiparous
214
What is the success rate of external cephalic version (ECV)?
~50%, >5% revert to breech
215
What can you use to relax the uterus?
Tocolysis (salbutamol or terbutaline)
216
What maternal intrapartum monitoring can you do?
- Vital signs, increasing in frequency as labour progresses
| - Progress "partography"
217
What fetal intrapartum monitoring can you do?
- Auscultation of fetal heart rate & pattern with Pinard stethoscope/hand held doppler/electronic monitoring with cardiotocography (CTG)
- Inspection of liquor once membranes are ruptured
218
Describe what you look at for Partograph?
- Fetal HR
- Rate of cervical dilatation
- Descent of fetal head
- Contraction characteristics
- Membrane ruptured- colour of amniotic fluid
- Volume of maternal urine
- Record of medications
- Maternal vitals
219
Describe the 3 layers to the anatomy of the uterus?
1. Perimetrium (serosa): thin outer layer of epithelium
2. Myometrium: thick middle layer of smooth muscle
3. Endometrium: inner layer with glands, blood vessels, lymphatics & epithelial cells
220
What are uterine contractions dependent on?
Gap junctions for phasic propagation of depolarisation (connexin 43 protein)
221
Describe the gap junctions in uterine smooth muscle?
- Inducible (especially hormonally)
| - Fundal dominance during labour may arise from anatomical arrangement of expressed gap junctions
222
What are the 2 receptor types effecting sympathetic outflow of the uterus?
- alpha-adrenoceptors: contraction
- beta-adrenoceptors: relaxation
(hormones influence the ratio of these receptors)
223
What are the posterior pituitary hormones which stimulate contraction of the uterus?
- Antidiuretic hormone (ADH)
- Vasopressin
- Oxytocin
(9 amino acid peptides, 2 amino acids different)
224
What is the effect & receptor numbers of oxytocin influence by?
Sex hormone levels
225
Describe the effect of oxytocin on uterine motility?
- Smooth muscle sensitive prior to labour due to increase oxytocin receptors
- Stimulates increasingly regular, co-ordinated contractions that travel from fundus to cervix
- Uterus relaxes between contractions
226
What is the purpose of uterine stimulants (oxytocics)?
- Induce abortion
- Induce & accelerate labour
- Contract the uterus after delivery to control postpartum haemorrhage (PPH)
227
What is the purpose of uterine relaxants (tocolytics)?
- Treat menstrual cramps
- Prevent preterm labour
- Facilitate obstetric manoeuvres
- Counteract (iatrogenic) uterine hyperstimulation
228
What are 3 oxytocic drugs used to stimulate uterine contractions?
1. Oxytocin (IV infusion to induce labour, IV or IM injection after delivery to control PPH)
2. Ergometrine
3. E & F series prostaglandins
229
Describe the use of Ergometrine oxytocic drug?
- Main use in obstetric haemorrhage (PPH)
- Bleeding early pregnancy (miscarriage)
- Causes sustained powerful uterine contractions
230
What is the drug Syntometrine?
Combination of Oxytocin & Ergometrine for 3rd stage of labour
231
What 3 places in the uterus has a significant prostaglandin synthesising capacity?
1. Endometrium
2. Decidua
3. Myometrium
232
Describe the difference classes of prostaglandins?
- Prostaglandin F2a (PGF2a): large amounts
- Prostaglandin I2 (PGI2)/ Prostacyclin: occur naturally
- Prostaglandin E2 (PGE2): occur naturally
- F series: vasoconstrictor
- E series: vasodilator
233
What are the 4 prostaglandin drugs & what are the equivalent to?
1. Dinoprostone: PGE2, naturally occurring
2. Carboprost: synthetic analogue PGF2a
3. Gemeprost: synthetic analogue PGE1
4. Misoprostol: synthetic analogue PGE1
234
What is Misoprostol (PGE1 analogue) used for?
- Room temp
- Treatment/prevention of peptic ulcers
- Medical abortion
- Induction of labour
- Control of postpartum haemorrhage (PPH) secondary to uterine atony
- Oral, vaginal, sublingual or rectal route
235
What are 5 examples of uterine relaxants (tocolytics)?
1. β2-agonists
2. Calcium channel blockers
3. Nonsteroidal anti-inflammatory drugs (NSAIDS)
4. Oxytocin receptor antagonist
5. Nitrates
236
Give 3 examples of β2-agonists and describe how they are used?
- Ritodrine, Terbutaline, Salbutamol
- Increase cAMP in smooth muscle
- Adverse effects: tachycardia, hypertension, hyperglycaemia
237
Give 2 examples of calcium channel blockers and how they are used?
- Nifedipine
- Magnesium sulphate
- Prevent intracellular Ca2+ increase in smooth muscle
238
Give an example of an NSAID and how they are used?
- Indomethacin
| - Inhibit prostaglandin biosynthesis
239
Give an example of an oxytocin receptor antagonist?
Atosiban
240
Give 2 examples of nitrates used for uterine relaxants (tocolytics)?
- Nitric oxide (NO) donors
| - Nitroglycerine patch
241
What does an imbalance of Prostaglandin E vs Prostaglandin F in endometrium cause?
Dysmenorrhoea & menorrhagia (excessive blood loss)
242
Why can NSAIDS be used to treat menstrual symptoms?
- Pain relief
| - May reduce blood loss by ~10%
243
What are the consequences of pre-term birth?
- Respiratory distress
- Hypothermia
- Cerebral palsy (Intraventricular haemorrhage)
- Hypoglycaemia
- Jaundice
- Sepsis
244
Who owns your body & its parts while you are alive?
Limited property rights as we don't have ownership but a "weaker package of limited property rights"
245
What is the key issue with saying we own & have property over our own bodies?
- You can typically transfer property (car, house etc) to someone else
- We have weak property right in that we can donate an organ, but don't have strong property right to sell
246
Who owns your body & its parts once you have died?
There is NO property in a corpse, so nobody owns it
247
Describe what happened in the Alder Hey hospital organ scandal in late 1990?
- Children dying of cardiac surgery had their organs stored
- Aborted or stillborn foetuses were kept
- Parents had consented to a post-mortem, but not to retention
248
What was the doctor at the centre of the Alder Hey Hospital scandal?
Professor Dick van Velzen (specialist in cot death)
249
How did Professor Dick van Velzen back up his illegal and unethical act?
"Children are too precious to die without using every scrap of information which could help the next child"
250
Describe the John Moore’s spleen case?
- John Moore was diagnosed with hairy cell leukemia
- Attended UCLA medical centre, & was under the care of David Golde
- Moore had spleen removed & returned to UCLA from Seattle several times to have blood & samples taken
- Golde had patented cell line derived from Moore's T-cells & products & was working in collab with pharma company making ~£15million
251
What did Moore do once finding out the truth about Golde using his samples for his own research without consent?
- Took him to court
- Asserted "continuing property interest" (conversion)
- Said he did not give informed consent & Golde had breached ethical duty
252
What was the conclusion from the court case between Moore & Golde?
- No property interest (removed spleen was not his property)
- Golde did breach ethical duty by not acting for patients benefit & should have ensured Moore was fully informted (financial fain was conflict of interest)
253
What is a "Continuing property interest" (conversion)?
“Where property belonging to one person is wrongly disposed of or converted to the use of another, to the detriment of its rightful owner” (Talbot, 2012)
254
Describe the Hagahai & T-cell case?
- US researchers collected samples
| - Created T-cell line and applied for a patent
255
What is a patent?
Government authority or licence conferring a right or title for a set period, esp the right to exclude others from making, using, or selling an invention
256
What ethical issues did the Hagahai & T-cell case raise?
Raises issues of "biopiracy", need for prior consent, discussion of benefit-sharing
257
What does the Tissue Act (Scotland) 2006 legally state?
Requires authorisation for use of organs, tissues & samples from the deceased
258
What legislation regulates the use of tissues from the living in Scotland?
NHS Scotland accreditation scheme (2011), now under Healthcare Improvement Scotland
259
What legislation regulates DNA analysis?
Consent as detailed in Human Tissue Act 2004 (England, Wales & N Ireland), there is an offence known as “DNA theft”
260
Describe how the Canavan gene patent controversy arose?
- Greenberg family affected by Canavan disease, father got scientist to look into disease, allowing his childrens tissues to be used
- Canavan gene testing price increased because patented by a hospital
- US supreme court "We hold that a naturally occurring DNA segment is a product of nature & not patent-eligible merely because it has been isolated”
261
What are the 2 main gene defects identified in familial breast cancer?
- BRCA1
| - BRCA2
262
Describe BRCA1 gene defect?
- Large families with breast & ovarian cancer
- Autosomal dominant
- Lifetime risk 50-80%
- Increases ovarian risk 40-50%
263
What is the Knudson hypothesis?
Two-hit hypothesis: cancer is the result of accumulated mutations to a cell's DNA
264
What does BRCA1 do?
- Human tumor suppressor gene
- Mutations mean protein shorter than normal
- C-terminus involved in DNA repair and binds to RAD50/51
- Stabilises the double strand break for BRCA2 to repair it
265
Describe the DNA damage response?
- If damage cells, BRCA1 location changes & overlaps with other proteins known to respond to damage
- When laser passed through nucleus, only region passed through will be damaged
266
Describe BRCA2 gene defect?
- >400 mutations
- Most result in truncated protein
- Founder effect
- Increases risk of prostate cancer & breast cancer
267
What does BRCA2 do?
- Binds to RAD51 protein
| - Responds to DNA damage, cells without BRCA2 particularly sensitive to DNA damaging agents
268
Describe the steps of Homology directed repair of DNA double strand breaks?
1. dsDNA break
2. Resection by exonuclease
3. Base-pairing with unwound DNA of undamaged sister chromatid
4. Strand extension
5. Disengage and pair
6. Fill in gaps, restore wild-type helix
269
Describe the steps of BRCA2 & DNA damage response?
1. BRCA2 recruits Rad51 to sites of DNA damage
2. BRCA2 promotes nucleation of Rad51 filament
3. BRCA2 stimulates Rad51-mediated strand exchange & D-loop formation
270
What are the 6 factors to consider in referral for genetic counselling?
1. Numer of family members affected
2. What generations?
3. Age of onset
4. Ethnic background
5. Breast cancer susceptibility genes have low penetrance
6. Polygenic disease?
271
How can you reduce the risk of breast cancer?
- Genetic testing
- Refer for screening (mammography/MRI)
i) Breast cancer
- tamoxifen 53%
- mastectomy >90%
- oophorectomy up to 68%
ii) Ovarian cancer
- Oophorectomy 96%
- Oral contraceptives 60%
272
What are 3 implications for treatment in potential breast cancer?
1. DNA damaging agents
2. DNA double strand breaks
3. Replication fork stalling
273
What is synthetic lethality?
2 genetic mutations are independently compatible with life BUT together cause mortality
274
What is PARP & what does it do?
- Poly ADP-ribose polymerase
| - Repairs single-strand DNA breaks by sending a signal to recruit other proteins
275
What is resistance in breast cancer?
- Over time small number of cells became resistant to PARP inhibitor
- Normal cells start to arise from resistant cell line
- Cell line starts off truncated with BRCA2 mutation.
- Small proportion repair some DNA (faulty)
- Instead of creating truncated protein, create essentially more functioning protein then started off with
276
What 3 things make you more susceptible to sporadic breast cancer?
- Early menarche
- Late menopause
- 1st child after 30 years
277
What % of tumours are oestrogen receptor (ER) positive?
~60%
278
Describe the hormone therapy of Tamoxifen?
- Prodrug
- Antagonist of oestrogen receptor
- Prevents expression of genes which would otherwise be stimulated by oestrogen
- Prophylactic after surgery for early stage breast cancer
- Side effect: hot flushes
279
What % of tumours are epidermal growth factor receptor 2 (HER2/erbB2) positive?
20-30%
280
What does HER2/erbB2 do?
Binds to growth factor receptor found on plasma membrane & causes signal transduction cascade which results in cells division
281
Describe Trastuzumab (Herceptin) treatment?
- "Humanised" monoclonal antibody to HER2
- Prevents signalling
- Suppresses HER2+ cancer cell growth & angiogenesis
- Cell mediated cytotoxicity
282
Describe when & why you would use Dozetaxel (Taxotere) as breast cancer treatment?
- Drug stabilises microtubules (key component of spindle)
- Promotes apoptosis
- Many tumours are aneuploid, may be because mitotic checkpoint isn't working
283
What are the risk factors for STI's?
- Young age
- Failure to use barrier contraceptives
- Non-regular sexual relationships
- Homosexuality
- IV drug use
- African origin (Sub-Saharan Africa)
- Social Deprivation
- Prostitution
- Poor access to advice & treatment of STIs
284
Describe Human Papillomavirus (HPV)?
- Induces hyperplastic epithelial lesions (genital warts)
- Types exhibit tissue/cell specificity
- Incubation period 1-6months
285
What are the different types of HPV warts which have varying potential to cause malignancy?
- Cervical carcinoma
- Urogenital warts
- Laryngeal papillomas
- Common, flat & plantar warts
286
What is the treatment for HPV?
- Podophyllum
- Cryo (freezing)
- Laser
- Surgery
287
What are the 2 killed vaccines available for HPV protection?
- Cervarix (bivalent)
| - Gardasil (quadrivalent)
288
Describe the HPV vaccine?
- Based on VLP1 (papillomavirus-like particle) a major capsid protein
- Given to girls 12-13yrs
- Protects against most cervical cancers
289
Describe Chlamydia trachomatis?
- Obligate, Intracellular, gram negative
- A,B,C serotypes: trachoma
- D-K serotypes: genital infection
- L1,L2,L3 serotypes: lymphogranuloma venereum cancer
290
What is a Trachoma?
Contagious bacterial infection of the eye, causing inflamed granulation on the inner surface of the lids, leads to fibrosis which causes the eyelids to contract & tighten causing it to be permanent (blindness)
291
What are the female & male symptoms for Chlamydia infection?
- FEMALE: discharge, abdominal & pelvic tenderness, infertility, Reiter's syndrome
- MALE: discharge, prostatitis, epididymal tenderness, Reiter's syndrome
292
What are the possible investigations you can do to test for Chlamydia?
- Urine: NAATs
- Endocervical swab: cell culture
- Antigen detection or EIAs
293
How do you treat Chlamydia infection?
Azithromycin & Tetracycline (doxycycline)
294
Describe Candida albicans?
- Vaginal discharge
- Yeast
- Normal microbiota of vagina
295
Describe thrush (UK) / Yeast infection (USA)?
- Intensely itchy vaginitis
- Present as UTI
- Diagnosed by microscopy/culture
- Recurrence common in women
- Rarely symptomatic in men
296
What is the treatment for Thrush (UK)/ Yeast infection (USA)/ Candida albicans?
Oral fluconozole & topical nystatin
297
Describe Trichomonas vaginalis?
- Anaerobic, single cell, flagellated protozoa
- Attaches to squamous epithelium
- Incubation 4d-3wk
- Infects vagina & urethra
- Causes trichomoniasis
- Yellowish vaginal discharge
- Diagnosed by dark-phase microscopy
298
How would you treat Trichomonas vaginalis infection?
Metronidazole
299
What are the 2 different types of Herpes Simplex Virus?
- HSV type 1 (HSV-1): oral region & causes cold sores
- HSV type 2 (HSV-2): genital infection (penis, anus, vagina)
CAN BOTH INFECT MOUTH &/OR GENITALS
300
Describe what happens in a person with Herpes Simplex virus?
Commonly asymptomatic but still shedding virus & infectious (responsible for most new infections)
301
What can neonatal herpes simplex virus infection cause?
Disseminated infection often involving CNS (severe neurological deficit)
302
Describe the primary infection of genital herpes (typically HSV-2)?
- Fever flu-like prodrome (5-7days)
- Tingling neuropathic pain in buttock, genitals, legs
- Bilateral crops of painful blisters/ulcers in genitals, vagina & cervix
- Tender lymph nodes
- Local oedema
- Dysuria
- Vaginal or urethral discharge
303
What do you treat genital herpes with?
Aciclovir
304
Why does recurrence of genital herpes occur?
- Following primary infection, virus becomes latent in local sensory ganglia
- Periodic reactivation
- Episodes usually shorter (<10days)
- Attacks become less frequent over time
305
What is the median recurrence rate after a symptomatic 1st episode in HSV-1 & HSV-2?
- HSV-1: ~1 attack in the subsequent 12 months
| - HSV-2: ~4 attacks in the subsequent 12 months.
306
How do you diagnose Herpes simplex virus?
- Clinical appearance
- Viral culture
- DNA detection using NAAT of swab from base of ulcer/vesicle fluid
- Serology to identify asymptomatic infection & distinguish between 2 types
307
How long may it take for HSV to become antibody positive after primary infection?
Upto 12 weeks
308
Describe Neisseria gonorrhoeae?
- Gram negative
- Intracellular diplococcus
- Infects epithelial cells of mucous membrane of GU tract/rectum
- Development of localised infection with production of pus
- Asymptomatic carriage in women
309
Describe the symptoms of Gonorrhoea in male & female?
- Acute inflammation & discharge in male
- Cervical discharge in female
- Rectal infections in male homosexuals
- Oral pharyngitis
- Disseminated infection (septic arthritis)
310
What is Ophthalmia neonatorum?
- Conjunctivitis contracted by newborns during delivery
- Mother infected with N. gonorrhoeae or C. trachomatis
- Can cause blindness without treatment
311
What lab diagnosis can you do for Gonorrhoea?
- Light microscopy of gram-stained genital specimens to look for gram-negative diplococci
- NAAT (urine)
- PMN in urethral pus
312
What are the 3 possible treatments for confirmed, uncomplicated gonococcal infection in adults?
- Ceftriaxone 250mg IM
- Cefixime 400mg oral
- Ciprofloxacin 500mg oral (if beta lactam allergy)
313
What antibiotic do most strains of gonorrhoea respond to?
Ceftriaxone
314
What may be given to treat patients with gonorrhoea & concomitant chlamydial infection?
Doxycyline
315
Describe Treponema pallidum?
- Gram negative spirochete
| - Causes syphilis
316
Describe the primary stage of syphilis?
- Hard genital or oral ulcer (chancre) at site of infection after about 3 weeks
- Asymptomatic for upto 24 weeks
317
Describe the secondary stage of syphilis?
- Red maculopapular rash (highly infectious) anywhere & pale moist papules in urogenital region & mouth (condylomas)
- Latent for 3-30 years
318
Describe the tertiary stage of syphilis?
Degeneration of nervous system, aneurysms & granulomatous lesions in liver, skin & bones (gumbos) in about 40% of patients
319
Describe congenital syphilis from mother to baby?
- Placental transfer after 10-15weeks of pregnancy
- Infection can cause death/spontaneous abortion of foetus
- Survivors develop secondary syphilis symptoms
320
How can you diagnose syphilis?
- Lesions or infected lymph nodes in early syphilis
- Dark field microscopy
- Direct fluorescent antibody (DFA) test
- NAAT
- EIA (can be for IgM in early infection, or IgG at 5 weeks or both)
321
Describe Haemophilus ducreyi?
- Causes chancroid
- Gram negative bacteria
- Painful genital ulcers
- Diagnosed by microscopy/culture
322
How do you treat Chancroid STI?
- Macrolide (ie. erythromycin)
| - Ceftriaxone
MD3002
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