Demo Study

Interleukin 10

• Helper T lymphocytes can be Th1 and Th2.
• Th1 is suppressed in pregnancy. Th2 increases
• Th1 produces cytokines TNF-alpha, IFN-y and IL-2
• Th2 produce cytokines IL-4, IL-5, IL-9, IL-10 and IL-13

In mouse studies IL-3 and IL-10 enhanced fetal survival and promote intrauterine growth while TNF-alpha, IFN-y and IL-2 had damaging effects in some cases resulting in fetal death

Reproductive Immunology

Immune Tolerance in Pregnancy

The fetus can be considered an allograft with antigenically different material to the mother. A number of mechanisms therefore need to be in place to prevent 'graft rejection' in the form of the mother mounting an immune response against the foetus. The placenta plays a key role here

Placenta
Immunological barrier between the mother and the fetus, creating an immunologically privileged site i.e. able to tolerate foreign antigens without provocation of immune response. A number of mechanisms help achieve this:

1. MHC (HLA complex) Antigen Expression

• It has been shown that differences between class 1 and class II Major Histocompatibility Complex (MHC) antigens are the basis for transplant rejection. In Trophoblast cells MHC class II antigens are not presented.
• HLA genes can be classes as 1a (HLA-A, -B, and -C) or 1b (HLA-E, -F, and -G)
• In trophoblast cells only HLA-C is expressed from the 1a group along with all three types of 1b genes.
• It has been shown that HLA-G in particular has several roles in immune suppression such as reduction of NK cell killing activity, reduction of IFN-y production, regulation of cytokine production and suppression of cytotoxic T lymphocyte killing activity and T-helper activity.

2. Complement Protein Inhibition

• DAF, MCP and CD59 are proteins expressed by the placenta that inhibit complement proteins. Complement is an important part of the immune system in graft rejections.

3.T-cells/T-helper cells

• Changes to both the cell populations occur during pregnancy. Increased T regulatory cell (TREG cell) populations occur in pregnancy. These cells can both up and down regulate various immune responses.
• Th2 levels increase during pregnancy
• Th1 levels decrease during pregnancy

4. Phosphocholination

• The addition of the phosphocholine molecule to glycoproteins inhibits T and B lymphocyte responses. It is a mechanism used by some parasites

5. PDL1

• Cell signalling molecule that down regulates T-cell response

6. Progesterone

• Thought to play a role in immune suppression by stimulating lymphocytes to produce a blocking factor that mediates cytokine production.

Other mechanisms

• Placental exosomes, retroviral envelope proteins and CRH may all play a role in maternal immune tolerance but this level of detail is unlikely to be required by the MRCOG

Absence of enteric neurons within the myenteric and submucosal plexus of the rectum and/or colon.

Oxybutynin

Drugs acting on the bladder

Anti-cholinergic agents

Oxybutynin, Tolterodine, Propiverine, Solifenacin, darifenacin, fesoterodine, flavoxate, trospium chloride Reduce involuntary bladder contractions with direct relaxant effect on the detrusor

Result in improvement in 57-71% of women with detrusor over-activity

Have significant placebo effect.

Side-effects, especially dry mouth appear to be less common with newer agents like tolterodine and solifenacin.

Oxybutynin - Side-effects include:

• Dry mouth (88%)

• Nausea, constipation, diarrhoea and abdominal discomfort

• Blurred vision

• Voiding difficulties

• Headache, dizziness, drowsiness, restlessness and disorientation

• Rash, dry skin, photosensitivity

• Arrhythmia  

• Angioedema

May precipitate angle closure glaucoma

Modified release preparation of oxybutynin has fewer side-effects and a trans-dermal patch is also available The efficacy and side-effects of tolterodine are similar to those of modified-release oxybutynin Flavoxate is less effective but has fewer side-effects

Contra-indications

• Myasthenia gravis

• Urinary retention / bladder outflow obstruction

• Severe ulcerative colitis, GI obstruction or intestinal atony

200 degrees

Transvaginal ultrasound scan

Normal morphology: 2%

Normal morphology should be 4% or more

Semen Analysis

The NICE quality standard [QS73] sets out reference ranges for semen analysis using the WHO guideline. They are as below:

• Semen volume: Greater than or equal to 1.5 ml
• pH: Greater than or equal to 7.2
• Sperm concentration: Greater than or equal to 15 million spermatozoa per ml
• Total sperm number: 39 million spermatozoa per ejaculate or more
• total motility (% of progressive motility and nonprogressive motility): 40% or more motile or 32% or more with progressive motility
• Vitality: 58% or more live spermatozoa
• Sperm morphology (percentage of normal forms): 4% or more

Other points from NICE guidance:

• Do not screen for antisperm antibodies
• If sperm count abnormal repeat in 3 months (or asap if azoospermia or severe oligozoospermia i.e. <5 million sperm/mL detected)

(A/A+C) ÷ (1 - (D/B+D))

Two types of likelihood ratios exist - positive (LR+) and negative (LR-).
Positive likelihood ratios tell us how likely a disease is if the test is positive, while the negative likelihood ratio tells us how unlikely a disease is if the test is negative.

They are calculated as:

LR+ = Sensitivity / (1 - Specificity)
LR- = (1- Sensitivity) / Specificity

A ÷ (A+C) is the calculation for sensitivity
D ÷ (B+D) is the calculation for specificity
A ÷ (A+B) is the calculation for positive predictive value

NOTE It has been noted the RCOG may ask you for the likelihood ratio and doesn't specify positive or negative. They have simply used sensitivity/specificity to calculate this. I can't find any statistical resources that support using this calculation method

Statistics

A = True Positive
B = False Positive
C = False Negative
D = True Negative

Sensitivity
Sensitivity is the ability of a test to correctly identify disease.
Sensitivity = A / A+C or True Positives/Number of people with disease

Specificity
Specificity is the ability of a test to correctly exclude a disease
Specificity = D / B+D or True Negatives/Number of people without disease

Positive Predictive Value
Positive predictive value = A/A+B or True Positives/All positive test results

Negative Predictive Value
Negative predictive value = D/C+D or True Negatives/All Negative test results

Likelihood Ratios
LR+ = Sensitivity / (1 - Specificity)
LR- = (1- Sensitivity) / Specificity

CVS

13.8%
The statistics published by HSCIC show postpartum haemorrhage effects 13.8% of deliveries in the UK

Labour

Labour has three stages:

• 1st stage: dilatation of cervix to 10cm
• 2nd stage: delivery of baby
• 3rd stage: delivery of placenta

Is associated with precipitation of globin chains within red cells

THALASSAEMIAS  

Defective synthesis of one globin chain in adult Hb causing precipitation of globin chains within  red cells and ineffective erythropoiesis and haemolysis

Beta Thalassaemia  

∙ Homozygous - no normal beta chain produced (ß0) or reduced beta chain synthesis (ß+). Excess  alpha chain combines with whatever beta, gamma or delta chain is available or precipitates,  causing haemolysis and ineffective erythropoiesis  

∙ Heterozygous beta-thalassaemia - usually asymptomatic microcytosis with mild anaemia  ∙ Over 200 genetic defects - mainly point mutations  

∙ Beta-thalassaemia minor - heterozygous carrier, low MCV and MCH but normal serum ferritin.  Hb electrophoresis shows raised HbA2 and HbF  

∙ Beta-thalassaemia major - homozygous, severe anaemia from 3-6 months old when switch from  gamma to beta chain occurs.  

∙ Extra-medullary haematopoiesis causes hepato-splenomegaly & bone expansion with typical  facies  

∙ Requires regular blood transfusions and folate supplementation  

∙ Iron overload from repeated transfusion treated with chelating agent desferrioxamine  

It is associated with oligohydramnios

Activates phospholipase-C which produces IP3 which triggers intracellular Calcium ion release

Oxytocin activates phospholipase C to produce inositol 1,4,5-trisphosphate (IP3), which releases Ca2+ from intracellular stores.

There are thought to be other mechanisms by which myometrium is stimulated by Oxytocin including increased sensitisation of the myometrium and increased calcium entry into cells.

cAMP and Protein Kinase A inhibit myometrial contractility.

Oxytocin

Oxytocin is a peptide hormone and neuropeptide produced by the hypothalamus and released by the posterior pituitary. Oxytocin aids mother-babybonding and stimulates breast milk production.

More heat production than coagulation current

CUTTING Vs. COAGULATION CURRENTS OF DIATHERMY

Low chloride, low sodium

This woman is producing a diuresis, this results from renal tubular damage due to the obstruction of the collecting systems.

Damage to the renal tubules causes an inability to concentrate urine, as a result there is a spectacular loss of sodium and water following relief of obstruction.

200 mg

During pregnancy maternal calcium homeostasis adapts to meet the calcium demands of the fetus, which is 200 mg daily in the third trimester with a total calcium accumulation of 30 grams. 

33

The spine is divided into 33 segments, 24 of which are mobile.

Simple columnar with subnuclear vacuolation

Requires biopsy of the embryo at the 6-10 cell stage

PRE-IMPLANTATION GENETIC DIAGNOSIS (PGD) 

• This requires IVF with biopsy of the embryo at the 6-10 cell stage. The indications  are as an alternative to pre-natal diagnosis in a couple known to be at risk of  transmitting a genetic disorder.

It can also be used as a primary tool in couples  undergoing IVF treatment.

Bacillus anthracis

BACILLUS SPECIES

• B. anthracis - gram positive aerobic spore-forming bacilli; capsulated

• Grows on blood agar

• Spores may remain dormant in the environment for several years

• Infects many animals including sheep

• Causes anthrax

• Produces an exotoxin

• B. cereus contaminates food such as boiled rice, causing food poisoning

Sensitive to penicillin

Follow Fraser's Law

Sagittal

Plasminogen activator

Glucose units up to 4 residues from a branch point

GLYCOGENOLYSIS  

∙ Phosphorylase catalyses the removal of glucose units by the phosphorylysis of alpha 1,4  glycosidic bonds up to 4 residues away from a branch point with the release of glucose-1  phosphate 

∙ Glucose-1-phosphate is converted to glucose-6-phosphate by phosphoglucomutase and this  can then enter glycolysis

∙ The liver, intestines and kidneys have glucose-6-phosphatase which can release glucose from  glucose-6-phosphate. Glycogen in skeletal muscle cannot be converted into glucose as  glucose-6-phosphate cannot leave cells 

∙ The three residues leading up to a branch point on glycogen are transferred to another part of  the molecule by transferase  

∙ Alpha-1,6-glycosidic bonds at branch points are cleaved by alpha-1,6 glucosidase

3000

D/B+D

Statistics

A = True Positive
B = False Positive
C = False Negative
D = True Negative

Sensitivity
Sensitivity is the ability of a test to correctly identify disease.
Sensitivity = A / A+C or True Positives/Number of people with disease

Specificity
Specificity is the ability of a test to correctly exclude a disease
Specificity = D / B+D or True Negatives/Number of people without disease

Positive Predictive Value
Positive predictive value = A/A+B or True Positives/All positive test results

Negative Predictive Value
Negative predictive value = D/C+D or True Negatives/All Negative test results

Likelihood Ratios
LR+ = Sensitivity / (1 - Specificity)
LR- = (1- Sensitivity) / Specificity

Delivery of the placenta by maternal effort

Physiological management  

Physiological management of the third stage involves a package of care which includes all of these three  components:  

1. No routine use of uterotonic drugs  

2. No clamping of the cord until pulsation has ceased  

3. Delivery of the placenta by maternal effort.  

Early suckling or nipple stimulation can increase uterine contractility. There is no evidence that early  suckling reduces the risk of PPH or other complications of the third stage.  

Cytokeratin , Carcinoma

12 hr

B1

The IMV drains to the splenic vein as shown below

Colon & Rectum Blood Supply

SMA = Superior Mesenteric Artery
IMA = Inferior Mesenteric Artery

NOTE: venous drainage mirrors the arterial supply

Images showing arterial supply to the large intestine

1 : 3000

Growth hormone

Puberty and Hormones :

Maximum growth velocity : Growth hormone
Thelarche : Estradiol
Menarche : Estradiol
Pubarche : Androgens

GI Tract initially forms via gastrulation from the endoderm of the trilaminar embryo around week 3. It extends from the buccopharyngeal membrane to the cloacal membrane. Later in development there are contributions from all three germ cell layers.

GI Tract Embryology

Most commonly seen in first born female babies

Congenital hip dislocation (CHD) has an incidence of 1.3 per 1000 of live births in the United Kingdom in unscreened populations.

In populations screened clinically with Ortolani and Barlow tests the prevalence is higher at 1.6‐ 28.5 per 1,000 and it is higher still with ultrasound screening

Family history is an important risk factor, a sibling with CHD increases risk by 5%. in CHD, 60% are first born and 85% are female. Another risk factor is prematurity.

There is a 17‐fold increase of CHD in babies born by vaginal breech and sevenfold in breech delivered by caesarian.

CHD is seen commonly in North American Indians who keep their babies' thighs adducted and less commonly in Africans and Chinese who carry their babies around their waists.

Clinical diagnosis is by the Ortolani test and ultrasound is used to confirm the diagnosis.