HD Flashcards
Anterior and posterior divisions of the Internal iliac
Anterior division.
- Obturator artery.
- Uterine Artery:
• Goes into a circuit with the ovarian artery (comes directly from the abdominal aorta).
• Gives off the vaginal branch (1/3 of vagina and cervix) and ascending branch (supplies uterus).
- Vaginal Artery (supplies lower 2/3 of vagina).
• Can also be branch of the uterine a.
Posterior Division
- Superior Gluteal
- Inferior Pudendal
- Inferior Gluteal
Lumbar Plexis important branches
Femoral: anterior compartment of thigh (L2, 3, 4)
Obturator: medial compartment of thigh (L2, 3, 4)
Genitofemoral: skin of scrotum/cremaster muscle/labium majorum (L1, 2)
Lumbosacral Trunk
fibres from L4 and L5 join = lumbosacral trunk, which emerges medial to the psoas, runs inferiorly over the pelvic brim and joins the sacral plexus
Pudendal Nerve to pelvic floor
(S2, 3, 4): leaves the pelvis through the greater sciatic foramen and then enters the perineum through the lesser sciatic foramen (goes around the sacrospinous ligament)
Travels through the pudendal canal - also, contains the pudendal artery/vein (IIA).
Pelvic parasympathetic to pelvic floor
(S2, S3, S4) to pelvic viscera.
Micturition, defecation, genital erection (point and shoot).
Sympathetic supply to pelvic floor
Allows filling of bladder and contraction of internal urethral sphincter (hypogastric), simulates contraction of the seminal vesicles and vas deferens.
Obstetric Anaesthetic Options
Spinal Aesthesia: subarachnoid space (L4-L5) - Complete anaesthesia below waist monitoring of uterine contractions
Pudendal Nerve Block:
Peripheral nerve block S2-S4: perineum and lower ¼ vagina - Mother can feel/assist contractions.
Caudal Epidural Block:
Administered to catheter in sacral canal (S1-S5) - Limbs unaffected.
Penis and Ovarian/testes Lymphatic drainage
Penis = drained by deeper Inguinal lymph nodes
Ovarian/testes = drained by Preaortic lymph nodes.
Infertility Definition
The failure to achieve a clinical pregnancy within 12 months of unprotected sex.
Primary infertility
Unable to ever bear a child
Secondary infertility
Unable to bear/ability to carry a child following a previous pregnancy
Spermatic Cord contents
Contains the vas deferens, testicular artery, genital branch (of the genitofemoral nerve), Pampiniform plexus, lymphatic vessels, tunica vaginalis.
Testes Blood supply and drainage
Supply:
Abdominal artery branches to form the gonadal testicular artery
Venous Drainage:
Right testicle = drained by to the inferior vena cava (also lies on the right side)
Left testicle = drained to the left renal vein (a lot longer).
Ovarian Cycle
Follicular phase: days 1 to 10
• 5-12 primordial follicles stimulated each month: one grows and matures.
• GnRH secreted from hypothalamus: stimulates anterior pituitary to secrete LH and FSH.
o These stimulates follicle to grow.
• Mature follicle secretes oestrogen.
o Inhibits further LH and FSH secretion by anterior pituitary (negative feedback).
o Stimulates growth of endometrium.
Ovulatory phase: days 11 to 14
• Negative feedback is temporary: oestrogen stimulates HPA resulting in burst of LH and FSH.
o Completion of meiosis I, onset of meiosis II in the oocyte.
Luteal phase: days 15 to 18
• Granulosa cells of mature follicle divide and form the corpus luteum
• Secretes progesterone and oestrogen. Prepares uterine endometrium for implantation
Menstrual Cycle
Menstrual phase (day 1-5): • Due to withdrawal of steroid support (oestrogen/progesterone) the endometrium collapses. • Endometrium is shed with blood from ruptured arteries (blood loss: 50-150ml).
Proliferative phase (day 6-14): • Oestrogen from mature follicle stimulates thickening of the endometrium. • Glands/spinal arteries form. • Oestrogen also causes the growth of progesterone receptors on endometrial cells.
Secretory phase (day 15-28): • Progesterone from corpus luteum: acts on endometrium. Enlargement of glands --> secret mucus and glycogen in preparation for implantation of fertilised oocyte. • No fertilisation = corpus luteum degenerates --> corpus albicans. Progesterone levels fall.
Conception Advice
Intercourse throughout the cycle (not just at certain parts)
No smoking, alcohol.
Reduce weight, stress, drugs.
Take folic acid (400mg).
Causes of Infertility
Ovulatory Causes (25%)
Tubal and Uterine Causes of Infertility (30%)
Unexplained Fertility
Ovulatory Causes of Infertility
Type 1: Hypopituitary failure (anorexia).
Management:
- Increase weight, decrease exercise.
- Consider pulsatile GnRH
Type 2: Hypopituitary dysfunction (e.g. PCOS, hyperprolactinaemia)
Management for HP: bromocriptine
Type 3: Ovarian Failure (premature ovarian failure if under 40 years).
- Involves persistent FSH raised.
Management: donor eggs, alternative parenting.
Polycystic Ovarian Syndrome
Diagnostic Criteria:
Clinical hyperandrogenaemia (excessive testosterone)
Oligomenorrhoea (infrequent periods)
Polycystic ovaries on ultrasound.
Menstrual disturbance, acne.
Raised LH with normal FSH, raised testosterone
Management:
First line: Clomiphene or metformin
Second line: combined clomiphene and metformin, laparoscopic ovarian drilling and Gn theraphy.
Tubal and Uterine Causes of Infertility
Pelvic Inflammatory Disease:
- Symptoms (NOTE: may be asymptomatic):
o Pelvic pain
o dyspareunia (painful sexual intercourse)
o fever.
(Investigate with full blood count and raised ESR).
Caused bacteria and STIs (chlamydia and gonorrhoea).
- Management: antibiotics, rest and abstinence.
Endometriosis
Symptoms:
o Pain
o Dysmenorrhoea (painful menstruation).
o Menorrhagia (abnormally heavy bleeding)
o Dyspareunia (difficult/painful sexual intercourse).
Management
• NSAIDs, COCP, GnRH agonists, surgery
Fibroids
• Benign tumours of smooth muscle of the myometrium (uterine leiomyoma).
o Complain of heavy, regular periods.
• Treated with (COCP), LARCs, surgical.
Male Factors of Infertility
- Testicular (infection, cancer, surgical, congenital and trauma)
- Azoospermia (absence of motile sperm).
- Reversal of vasectomy.
- Ejaculatory problems (retrograde and premature).
- Hypogonadism.
Assisted Conception
Intrauterine Insemination (IUI): Sperm is separated in lab, removal of slower speed sperm before partner is inseminated - tried 12 cycles before IVF
In-Vitro Fertilisation (IVF): o Women under 40 who have not conceived after 2 years of unprotected intercourse o Women 40-42 offered one cycle if: Never had IVF. 6 or more UII cycles. No evidence of low ovarian reserve.
Intracytoplasmic Sperm Injection (ICSI):
• Single sperm injected directly into egg.
• Is offered to:
o Severe deficits in semen quality
o Obstructive and non-obstructive azoospermia.
o Failure of IVF treatment.
Function of the Prostate
Makes about 30% of alkaline seminal fluid that contains an anticoagulant (PSA) to that sperm can swim and survive in the female vaginas acidic environment.
Regions of the Prostate
Peripheral Zone (PROSTATE CANCER) Central Zone Transition Zone (BENIGN PROSTATE ENLARGEMENT)
Testosterone Proliferation and Apoptosis in Benign Prostatic Hyperplasia
Stromal cells: converted to estradiol
• Causes stromal cell proliferation (binds to ER alpha).
Epithelial cells: converted to DHT and prevents apoptosis.
Signs and Symptoms of Benign Prostatic Hyperplasia
• Weak/interrupted flow of urine. • Frequent urination (nocturia). • Trouble urinating. • Pain/burning during urination. o Blood in urine/semen
SHITE = slow stream, hesitancy, intermittent flow, terminal dribbling, emptying incomplete. FUN = frequency, urgency, nocturia.
Diagnosis of Benign Prostatic Hyperplasia
Diagnosis:
• History
• Digital Rectal Exam (DRE)
• Ultrasound (biopsy) = allows an estimate of the width/height/length of prostate.
• Blood test = PSA (gamma-seminoprotein or kalikrein-3)
Treatment of Benign Prostatic Hyperplasia
Pharmacotherapy.
o Alpha-1 adrenergic blockers - Relaxes smooth muscle in bladder and prostate (Tamulosin).
o 5-Alpha-reductase inhibitors - Tries to block conversion of testosterone to its active form (dihydrotestosterone). DHT normally binds to androgen receptor causing cell proliferation.
Two types: dutasteride and finasteride
Surgery
o Transurethral resection of the prostate - Cuts out transitional zone but leaves PZ
Done when:
• Urinary tract infection.
• Recurrent gross haematuria.
• Failed voiding trials.
• Renal insufficiency secondary to obstruction
Open Prostatectomy
o For very large prostates (>75g)
Laser Ablation/Transurethral Microwave/High Energy US Therapy
• Going through urethra with laser (will cook TZ cells and kill them so you can increase size).
Urolift: opening of urethra
Prostate Cancer
Symptoms of BHP may be like prostate cancer - PSA tends to be much higher than in BPH
Mechanism of Smooth Muscle Relaxation in Erection
- Non-adrenergic non-cholinergic parasympathetic neuron releases nitric oxide.
a. Diffuses across to smooth muscle - NO binds to soluble guanylyl cyclase and produces cGMP
- This causes smooth muscle relaxation (decreases calcium inflow).
a. Signals from the sympathetic neuron does the opposite.
Treatment of Erectile Dysfunction
Can target cGMP and stop its breakdown to cause relaxation. E.g. • Phosphodiesterase type 5 inhibitor: o Sildenafil (Viagra) o Vardenafil (Levitra) o Taladafil (Cialis)
Peyronie’s Disease (Bent Penis)
Scar tissue forms on shaft of penis
Where do varioceles in the testes usually develop
ALWAYS in the left testis.
Types of Miscarriage
Threatened: light/painless bleeding from vagina (PV)
• Fetus is alive - cervical os is closed
Inevitable: bleeding heavier vs threatened.
• Fetus may be alive at this point - cervical os is open.
o Miscarriage about to occur.
Incomplete: only some of the fetal parts have passed.
• Cervical os is open.
• PV bleeding continues.
Complete: All fetal tissues have been passed.
• Bleeding has diminished stopped.
• Uterus no longer enlarged - cervical os is closed
Septic: contents of uterus infected = endometritis.
• Tender uterus, fever may be absent.
• May progress to pelvic infection.
Missed
• Fetus has not developed and died in utero.
o Cervical os is closed
Causes of Recurrent Miscarriage
Causes: • Autoimmune disease (e.g. anti-phospholipid syndrome): 25%. • Chromosomal defects (4%). • Hormonal factors • Anatomic factors. • Infection. • Others
Presentation of Ectopic Pregnancy
Clinical Presentation
• Women of reproductive age with PV bleeding.
• Lower abdominal pain.
• Collapse (shoulder tip pain).
• Amenorrhoea for 4-10 weeks (absence of menstruation)
Molar Pregnancy/Gestational Trophoblastic Disease
When trophoblastic tissue that forms part of blastocyst proliferates more aggressively than normal
Hydatidiform mole: no fetus, only the placenta forms
Partial Hydatiform: some evidence of embryonic development can be found
Examination
• Large uterus
• Early pre-eclampsia and hyperthyroidism may occur.
Investigations
• Ultrasound: snowstorm appearance.
Infections in Pregnancy
TORCH
Toxoplasmosis Other (influenza, parvovirus B19) Rubella Cytomegalovirus (CMV) Herpes Simplex Virus, HIV, Hepatitis.
Congenital Cytomegalovirus Symptoms
Wide Range Symptoms
• Severe: intra uterine growth retardation (IUGR) –> very non-specific.
o Hepatosplenomegaly, microcephaly.
o Sensorineural deafness (commonest congenital cause)
Treatment: • IV Ganciclovir OR • Valganiclovir (pro-drug of Ganciclovir) o Inhibits DNA synthesis. o Oral medication.
Congenital Varicella Syndrome Symptoms
Symptoms:
• Skin lesions (73%): limb hypoplasia
• CNS (62%): microcephaly, hydrocephaly, neurodevelopmental delay.
• Cataracts/other eye problems.
• GI, Genitourinary and cardiac abnormalities
Neonatal HSV Infection treatment
Acquire infection while passing through birth canal (and kissing the child)
Management
• Mortality (untreated) 65% reduced to 25% with aciclovir treatment
Congenital Rubella
The risk is greater the earlier there is contraction. Risks involve: o Microcephaly o Heart disease o Petechiae and purpura.
Congenital Toxoplasmosis
Mother infection due to parasite toxoplasma gondii ( Natural host is cat)
Clinical Features: IUGR (intrauterine growth restriction), hydrocephalus, cerebral calcification, microcephaly, hepatosplenomegaly.
Syphilis
Sexually transmitted infection due to spirochete Treponema pallidum.
Treatment: penicillin
Congenital Syphilis: Early 0 to 2 years • Rash • Rhinorrhoea (thin clear nasal discharge) • Osteochondritis • Perioral fissures • Lymphadenopathy
Late i.e. >2 years • Hutchinson’s teeth • Clutton’s joints • High arched palate • Deafness • Saddle nose deformity • Frontal bossing
Stages of Labour
1st Stage of Labour Latent Phase: 0-3cm cervical dilatation. Active Phase: 3-10cm cervical dilatation. • Primigravida: 1-3cm/hr. • Multigravida: 3-6cm/hr.
2nd Stage of Labour
Primigravida: 40 minutes
Multigravida: 20 minutes.
• Propulsive phase: from full dilation to present part reaching pelvic floor.
• Expulsive Phase: from reaching the pelvic floor to delivery of the baby
3rd Stage of Labour
• From delivery of the baby to expulsion of the placenta (30 mins)
Macrosomia causes
- Maternal diabetes (common).
- Maternal Obesity
- Previous large babies
- Prolonged pregnancy
Management of Failure to Progress in pregnancy
Powers: Uterine Inertia (absence of effective contractions).
o Give syntocinon (oxytocin)
Passenger: Malpresentation or malposition.
o Consider ECG/rotation forceps/C-section
Passages: contracted pelvis/rigid cervix.
o C-section.
Signs of Foetal Distress in Labour:
• Meconium (faeces in abdomen due to distress)
• Fetal heart rate abnormalities
o Bradycardia <110/mt, tachycardia >160/mt
• Decelerations.
Closure of Foetal circulatory vessels
Closure of ductus arteriosus (increased oxygen levels).
o In utero ductus is kept open under influence of PG E1
• Closure of foramen ovale.
o Due to drop in pressure in pulmonary circulation/right side of heart.
Shunting is reversed and valve closes
• Closure of ductus venosus.
o Due to decrease in blood flow in inferior vena cava.
What causes the blue look in cyanosis
Amounts of deoxygenated Hb
Deoxygenated Hb >50g/l in capillaries OR >34/l in arterial blood
Eisenmenger shunt
Pulmonary oedema impairs gas exchange (increased PAP from left –> right shunts)
Pulmonary hypertension causes right to left shunting as there is higher pressure on right side
Neural Tube Defects
Spina Bifida Occulta = failure of one or more vertebrae in spine to form properly
o Myelomengocoele is the most serious form (neural tissue exposed on babies back)
Meningocoele = meninges protruding from spinal column.
Encephalocoele = protrusion of neural tissue (brain) from head.
Anencephaly = absence of major portion of brain, skull, and scalp.
Treatment and consequences of Myelomeningocele
Closure reduces risk of infection but does not restore normal neural function.
Also: closure may lead to hydrocephalus (build-up of CSF).
o Treated with a plastic catheter that is put through the valve and runs under the skin into the peritoneal cavity to be rapidly absorbed into the circulation
Consequences:
Mixed sensory, motor and autonomic problems.
o Dependent on level of lesions and degree of neural disruption.
Loss of bladder control, faecal incontinence and loss of sensation in legs.
Abdominal Wall Defects
Gastroschisis (abdominal cavity open)
Exomphalos (Herniation through umbilical cord)
Causes of Primary Post-Partum Haemorrhage (PPH)
Are traditionally the 4Ts:
T: Tone = uterus not contracting (70%)
T: Tissue = placenta/membranes left behind (20%)
T: Trauma = episiotomy/tear which keeps bleeding (9%)
T: Thrombin = clotting disorders that need to be corrected (1%).
Management of Primary PPH
Uterotonics • Syntometrine (oxytocin and Ergemetrine). o Syntocinon (synthetic oxytocin). o Ergemetrine (vasoconstriction). • Misoprostol (prostaglandin E1) • Carboprost (prostaglandin F2alpha).
Surgery
• Bakri Balloon: device used for the temporary control and reduction of PHH (inflates: keeps uterus contracted and stops bleeding).
• B-Lynch: mechanical compression of atonic uterus using sutures.
Uterine Artery Embolization (catheter to deliver small particles that block the blood supply to uterine body).
(!) Resort to hysterectomy (removal of uterus) sooner rather than later
• Especially in cases of placenta accreta (vessels grow too deeply into uterine wall)/uterine rupture.
Causes of Secondary PPH
Infection: endometritis (Commonest cause of postnatal morbidity)
Tissue: Retained products of conception (RPOC).
Psychiatric Disorders in pregnancy
Postpartum Blues
Postpartum/Perinatal depression
Postpartum/Puerperal psychosis
Pregnancy-Induced Hypertension (PIH)
Gestational hypertension: late onset hypertension, without proteinuria.
Pre-eclampsia: hypertension with proteinuria and after 20 weeks of pregnancy.
Eclampsia: pre-eclampsia and convulsions (one or more).
Control of Fits treatment in eclampsia
Loading Dose: MgSO4 (8mls + 12mls saline) over 20 minutes
Maintenance Dose: 1-2g MgSO4/hr (20 + 30)
o Maintain for 24 hours post-delivery
Therapeutic Levels: 2-4mmol/litre.
Apgars Scoring
o Appearance o Pulse o Grimace o Activity o Respiration o Skin Colour
Perinatal Asphyxia/Hypoxic-Ischaemic Encephalopathy
Medical condition result from deprivation of O2 to a newborn infant (usually harm to brain)
Clinical Presentation:
•Infant needs resuscitation at birth. Presents with
o Absent heart rate, infant not breathing
o May require airway, respiratory and haemodynamic support
o Infant subsequently encephalopathic.
Abnormal neurological function.
Abnormalities of tone and reflexes
Autonomic dysfunction
Seizures.
Prevention of Secondary Energy Failure after Perinatal Asphyxia
Decrease energy depletion. Glutamate (inhibition of release). Inhibition of leukocyte/microglial/cytokine effects. Blockage of downstream cellular events. o Free radical synthesis inhibitors o Free radical scavengers etc…
Infection of the Newborn
Major cause of mortality and morbidity
GBS (group B streptococcus) and E. Coli.
Early-Onset GBS: • Apnea (stop breathing in sleep) • Severe hypoxia • Cardio-respiratory failure • Hypotension • Metabolic Acidosis • Tachycardia • Poor perfusion
Treatment
• Amikacin and gentamicin.
Low birthweight classes
Low Birthweight (LBW) = <2500g
Very Low Birthweight (VLBW) = <1500g
Extremely Low Birthweight (ELBW) = <1000g.
Edwards syndrome affects which chromosome
Trisomy 18
Presents with:
Decreased muscle tone, low set ears, overlapping fingers or clubfeet
Neonatal Problems with SGA Baby
Temperature control:
Increase SA to volume ratio
Reduced adipose tissue insulation
Reduced capacity for thermogenesis.
Polycythaemia (increased RBCs) - Due to being hypoxic in utero –> thickened blood
Poor nutritional status = URGENT: treated with:
- Feeds
- Bolus of dextrose + IV infusion.
Respiratory distress syndrome (RDS)
Surfactant deficiency
Signs of respiratory distress: tachypnoea, expiratory grunting, recession.
- Within 4 hours of birth.
Presentation
o X-Ray = ground glass appearance
Air bronchogram (air in villus not in lung).
Acute Complications of HMD
o Air leaks to increased pressure to inflate lungs.
o Pneumothorax if air leaks through pleura.
o Pulmonary intestinal emphysema.
Air in interstitium (increased respiratory distress).
Prevention: Ante-natal steroids. Avoidance of intrauterine hypoxia. Prophylactic surfactant treatment. Keep warm, avoid acidosis.
Treatment:
Surfactant and respiratory support.
Cardiovascular problems with premature
PPHN (Persistent Pulmonary Hypertension of the Newborn) - Lung vessels do not relax and are constricted: blood flow is suboptimal
Failure to maintain blood pressure
Patent Ductus Arteriosus - Connects the pulmonary artery and the aorta.
• Can cause excessive pulmonary blood.
What can excess feeding in the premature cause
may precipitate necrotising enterocolitis (NEC)
Necrotising Enterocolitis
Acute bacterial invasion/ inflammation/necrosis of bowel gas formation in bowel wall (pneumotosis)
Clinical Presentation
o Abdominal distension, tenderness, discolouration.
o Blood in stools.
o Generalised collapse
Hospital Acquired Infections in premature
Coagulase negative staphylococci.
Gram negative organisms (colonise the intestine).
Neurological problems in the premature
Susceptibility to periventricular haemorrhage (PVH)
• Poor control of brain perfusion.
• If sudden increase (release of pneumothorax) increased flow.
o On the walls of the third ventricle: germinal matrix.
Lots of neurons that migrate to the cortex.
Susceptibility to bleeding (no scaffolding).
Risk of Periventricular Leucomalacia (PVL).
• Ischaemia of periventricular white matter.
o Area where ACA and MCA meet: very susceptible.
IVH Classification
Stage I: haemorrhage in the matrix.
Stage II: IVH without ventricular dilatation.
Stage III: IVH with enlarged ventricles.
Stage IV: IVH with parenchymal haemorrhage.
Fanconi anaemia
failure of DNA to repair itself properly.
o Genetic cause; FANC as well as FANCA.
Work together to ubiquitinate two proteins.
Aetiology of Gestational Diabetes
Pregnancy, intrinsically, is a state of insulin resistance and glucose intolerance.
o Due to placental secretion of anti-insulin hormones (HPL, cortisol and glucagon)
Gestational diabetes: exaggeration of this.
o Often due to increased genetic and environmental risk.
When to screen for Gestational Diabetes
26-28 weeks - Don’t screen earlier: physiological drivers that are diabetogenic not yet present.
Gestational Diabetes effect on the baby
Mother has higher blood sugar levels
Glucose is small –> crosses placenta into fetus
Macrosomic Baby: fetus will get fat as it stores glucose.
o Also, large for gestational age
Polyhydramnios: because baby is bigger it will urinate more
(Unexplained Stillbirth): because baby is too big it will not have enough nutrients.
Gestational Diabetes Fetal Complications
- Macrosomia (birth asphyxia and traumatic birth injury).
- Respiratory Distress Syndrome (low surfactant)
- Hypoglycaemia (baby loses flood of glucose supply).
- Hyperbilirubinemia (jaundice).
Drug used for Gestational Diabetes treatment
Metformin (only one not teratogenetic)
Urinary Tract Infections in pregnancy
More common in pregnancy (pressure of fetus on tubes (ureter and urethra) and bladder causes stasis)
Treatment matters (even if asymptomatic) because of risk of complications: o Maternal: pyelonephritis (infection of one or both kidneys) o Fetal: growth restriction, preterm labour.
Treatment:
• Penicillin’s
• Cephalosporins
• Nitrofurantoin.
Listeriosis
Rare but can be fatal.
Often asymptomatic or just “virus” symptoms.
Criteria for Further Assessment for Growth in the child
Weight/height or BMI is below the or 0.4th centile.
Unless already investigated
Height centile is more than 3 centile spaces below mid-parental centile
Drop in Height Centile Position of more than 2 centile spaces.
Phase of Growth and driving factors
Infancy: rapid growth (nutritionally determined, up to two years)
Childhood: relatively steady (primarily regulated by GH and T4)
Puberty: acceleration and then cessation (GH, sex steroids, T4).
Turner’s Syndrome
Missing whole/part of X syndrome.
Benefit from growth hormone (early diagnosis is key).
o Therefore, all short stature girls need karyotype analysis
Short stature Webbed neck Widely-spaced shield nipples Cubitus valgus (angulation of forearm) Lymphedema of hands Knock knees Shortening of 4th/5th metcarpal
Management of Idiopathic Short Stature in Children
Administration of GH
Oxandrolone
o Very little change in most cases.
Do not recommend growth hormone therapy unless immense psychological effects.
Tests for Systemic Disorders in Children
Complete blood count, Na/K+/Cl/Bicarbonate.
Kidney function tests (blood urea nitrogen)
Insulin-like growth factor -1
Immunoglobulin A (IgA), tissue transglutaminase (CD).
Action of Somatostatin on Growth Hormone
Inhibitory –> determines peak pulses of GH (every 3-4 hrs)
Most Common cancer in:
0-14 Year Olds
15-19 Year Olds
0-14:
• Leukaemia (31.1%),
• CNS (25.4%),
• Lymphomas (10%).
15-19: • Lymphomas (20.7%), • Carcinomas and Melanoma (19.6%) • CNS (18.7%) • Leukaemia (13.8%).
Oncogenes activation
DOMININANT (One allele activation) A gain of function. Activated by: o Mutation o Chromosome Translocation o Gene Amplification o Retroviral Insertion.
Tumour Suppressor Inactivation
RECESSIVE (both allele dysfunction - no functional gene) Inactivated by o Mutations o Deletions o DNA Methylation (epigenetic)
Wilms Tumour
Aggressive tumour of the kidney (known as Nephroblastoma) consisting of pluripotent embryonic renal precursors (Blasterma, Epithelia, Stroma)
Asymptomatic abdominal mass without metastasis.
o Spreads by growth or via lymphatics/blood stream
Somatic genetic alterations:
• Inactivated WT1, WTX, TP53 genes.
• Activated CTNNB1 (beta catenin) gene (oncogene).
• Epigenetic alterations at IGF2/H19 locus.
(!) WT1 has a key role in ureteric branching.
• WT1/WNT (activated by beta catenin): key roles in epithelial induction of metanephric mesenchyme.
Retinoblastoma
Tumour of the retina (Loss of RB1)
Symptoms: leukocoria (white pupil when light shone into it), eye pain or redness, vision problems.
Cancer Cells without RB1: if you don’t have RB1: E2F is free to induce G1-S transition.
Activation of MYCN: proliferation.
Neuroblastoma
Tumour of the SymNS in adrenal gland/sympathetic ganglia
Derived from sympatho-adrenal linage of the neural crest during development.
o Originates from incompletely committed precursor cell.
Key genes: MYCN, ALK.
Treatment:
Surgery, chemotherapy, radiation theraphy.
Targeted Theraphy
• Crizotinib against ALK mutations
Immunotherapy
Acute Lymphoblastic Leukaemia
MOST COMMON MALIGNANCY in children
Symptoms
• Bruising/bleeding.
• Pallor or fatigue due to anaemia.
• Infection due to neutropenia (few white blood cells)
Pro-B: CD19+ on the cell surface.
Pre-B: CD19+ and CD10+.
These have very specific genetic changes that cause different types of leukaemia’s.
• ALL: MLL translocation (19) (most common)
• TEL-AML1 translocation (19 and 10)
Standard Treatment Phases • Induction • Consolidation • Maintenance • Bone marrow transplantation.
Chlamydia Trachomatis
Serovars D-K
• Males: urethritis, epididymitis, prostatitis
• Females: cervicitis, PID (pelvic inflammatory disease), Fitz-Hugh Curtis (inflammation of stomach and liver lining)
• Neonate: conjunctivitis (pink eye) and pneumonia.
Serovars L1-3
• Lymphogranuloma Venereum (chronic infection of the lymphatic system) (LGV).
o Buboes = swollen inflamed lymph node
o Proctitis = inflammation of the rectum/anus
Complications
• Reactive arthritis
• Infertility
Treatment
• Azithromycin
• Doxycycline
Genital Warts
Human Papilloma Virus (DNA)
Some are associated with carcinoma (16, 18, 31, 33)
Management.
o Topical Podophyllotoxin
o Imiquimod
o Cryotherapy
Neisseria Gonorrhoea
Symptoms:
• Males: urethritis, prostatitis, sore throat, epididymitis, prostatitis
• Females: cervicitis, PID, peri-hepatitis, septic abortion (infected while pregnant)
• Neonates: conjunctivitis
Complications: septic arthritis (bacteria spreads through the joints), blindness, infertility, septicaemia (blood poisoning by bacteria) –> meningitis, endocarditis.
Management:
Ceftriaxone: antibiotic.
Herpes Simplex Virus 1 and 2
HSV-1 = Oral HSV-2 = Genital.
Blisters that scab over
Two main presentations: Disseminated HSV • Sepsis-like syndrome • Hepatitis, coagulopathy • High mortality • IV aciclovir
HSV Encephalitis
• Fever, seizures
• Haemorrhagic infarction of white matter/cortex
o Particularly in temporal lobes.
Management (Not curable)
• Aciclovir
• Famciclovir
• Valaciclovir.
Treponema Pallidum (Syphilis)
Primary:
Chancre (genital ulcer disease - painless so unnoticed)
o Highly infectious ++
Secondary:
Condyloma Lata (wart-like lesions on genitals)
o Highly infectious ++
Latent, Tertiary, Congenital.
o Often asymptomatic in early stages.
Diagnosis depends on serology.
Treatment (Curable)
• Penicillin.
• Doxycycline.
HIV
HIV infects CD4+ T cells (T-helper cells), macrophages and dendritic cells. o Acute (primary) HIV infection leads to massive loss of CD4+ cells. o Chronic HIV infection leads to on-going loss of CD4+ cells, decline in immune function and progressive immunosuppression
HIV-associated disease incorporates:
o Direct effect of HIV: wasting, diarrhoea, neurological problems
o Opportunistic Infections: viral, fungal, bacterial, mycobacterial and parasitic infections
o Malignancies: lymphoma, cervix carcinoma.
Retroviral Theraphy
• HAART: highly active antiretroviral theraphy.
o 6 classes of antiretroviral drugs.
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
NNRTIs (Non-NRTIs)
PIs (Protease Inhibitors).
Fusion Inhibitors.
Integrase Inhibitors.
Co-receptor antagonists.
o Always combine at least 3 from 2 classes.
• Act during viral replication cycle.
Problems with HAART therapy (against HIV)
Side Effects
Short-Term:
• Nausea/vomiting/headache.
• Sleep disturbance.
Long-Term • Lipodystrophy (lose fat in some parts and gain in others) • Renal dysfunction. • Peripheral neuropathy. • Lactic acidosis.
Wheezing in intra and extra-thoracic airways
Anything related to obstruction of intrathoracic airways = wheeze of expiration
Wheezing is fluttering between slight and greater narrowing:
• Can be caused by airway swelling
Anything related to obstruction of extrathoracic airways = wheeze of inspiration
• Often related to croup. – upper airway infection, characteristic barking cough
Preschool Wheeze
Episodes of wheeze usually triggered by cold
Treatment:
1) Short-acting beat 2 agonist
2) Inhaled steroid or Leukotriene receptor agonist (LTRA)
3) Inhaled steroid and LTRA
4) Paediatrician
Asthmatic cellular effects
- Goblet cell hyperplasia.
- Thick subbasement membrane.
- Cellular infiltrate.
Bacteria with exotoxins
o Exotoxins: bacterial toxins secreted by the host.
Cholera: opening of CL- channels that lead to water into gut.
Diphtheria: sore throat with pseudo membrane
• Diphtheria Toxin A inhibits protein synthesis. Acts on:
o Heart: myocarditis and heart block.
o Nerves further difficulty swallowing, paralysis, diplopia (d. vision)
Septicaemia and Meningitis in children causes and symptoms
Steptococcus pneumoniae
Neisseria meningitides
Haemophilus influenza B (HiB)
Clinical Symptoms of Septicaemia • Tachycardia. • Tachypnoea. • Prolonged capillary refill. • Low BP (late sign) • Rash.
Clinical Symptoms of Meningitis • High temperature • Headaches • Vomiting • Not able to tolerate bright lights. • Drowsiness • Stiff Neck.
Meningitis official diagnosed through lumbar puncture (>3 months)
Tetanus causes
Gram-positive bacillus
Spores found in soil.
Organisms in Young Infants
- Group B streptococcus.
- E. coli.
- Listeria
Young infants = combination of Cefotaxime/Ceftriaxone AND Amoxicillin (needed for listeria cover).
• Older children just need Ceftriaxone.
Immune Defects Predisposing to Pneumococcal Infection in childhood
Absent/non-functional spleen.
o Vulnerable to encapsulated bacteria (pneumococcus, HiB, meningococcus).
Congenital asplenia
Traumatic removal
Hyposplenism
o Need vaccination and lifelong penicillin.
Hypogammaglobulinaemia. (low immunoglobulins)
HIV Infection.
Invasive and non-invasive streptococcal diseases in childhood
Non-invase: acute otitis media, sinusitis, conjunctivitis, pneumonia.
Otitis Media: normally pneumococcus sit in the nasopharynx.
o Children tube: more straight.
Invasive: pneumonia, septicaemia, meningitis, peritonitis, arthritis.
Pneumococcal Pneumonia: lobar and empyema.
o Empyema: chest drain and Urokinase.
Also, managed by VATS.
Vaccination for streptococcal diseases
Pneumococcal Polysaccharide Vaccine (PPV)
Pneumococcal Conjugate Vaccine (PCV)
Fungal Infections
Superficial Mycosis (Common): o Candidiasis: nappy rash. o Tinea Corporis: ring worm. Treat both with topical antifungal (nystatin). • Occurs in Normal Hosts
Invasive Mycosis (Rare):
o Candidaemia: extremely preterm infant, effects kidneys and brain.
o Pulmonary Aspergillosis: child with chronic granulomatous disease.
Impaired neutrophil function
• Opportunistic infections in immunocompromised hosts.
Protozoa Infections in childhood
Malaria
Four main species of Plasmodium species:
- falciparum, viva, ovale and malariae
Toxoplasma gondii (toxoplasmosis)
Cryptosporidium (diarrhoea).
What can be used in rapid diagnosis of trisomy 21
fluorescence in situ hybridization (FSH
Down Syndrome important considerations
Cardiac Assessment (echocardiogram): between 40-60% = congenital heart defect. o 30-40% are complete atrioventricular septal defects
- Hearing Tests: sensorineural hearing loss
- Ophthalmology: tenfold increase in congenital cataract/infantile glaucoma
- GI Check: 7% have GI problems
Assessed again at three months.
A1555G Mutation
Penetrance of hearing loss following aminoglycoside (antibacterial) exposure
Leads to:
• Communication difficulties
• Academic difficulties
• Social functioning difficulties.
Types of Sudden Unexplained Death in childhood
Baby is found dead in the cot:
o SIDs.
o Congenital heart disease.
Acute myocarditis.
Fibromuscular dysplasia of CAs.
o Respiratory infections.
o CNS infections
o Septicaemia
o Unsuspected liver tumour
Baby dies in parents/carers arms (instantaneous death):
o Cause of death is obvious
o Cause of death is not apparent
Rapid death due to a recognised illness:
o Respiratory infections
Severe bronchopneumonia
o CNS infections
Meningitis (see micro).
• Waterhouse-Friderichsen (group of symptoms due to adrenal dysfunction)
• DIC: disseminated intravascular coagulation
o Gastroenteritis.
o CNS Haemorrhage.
How does Petechiae in the thymus look
Starry sky pattern.
White: macrophages eating up lymphocytes (dark).
Sudden infant death syndrome (SIDS) triple risk hypothesis
Critical Developmental Period
• Developmental immaturity.
• Rapid changes between 2 and 4 months.
Vulnerable Infant • Males 60%. • Abnormality of serotonergic network. • Slower responses to changes. o Increases in heart rate/breathing. • Alterations in heart ions channels.
External Stressor • Minor URTI (upper respiratory tract infection) • Prone position • Bed-sharing • Overheating • Hyperthermia.
Enveloped and non-enveloped viruses
Enveloped Herpes virus: • Herpes simplex virus • Cytomegalovirus • Varicella Zoster • CMV • Epstein-Barr • HHV 6/7/8. Hepatitis B Poxviruses.
Non-enveloped PAP: • Papillomavirus • Adenovirus • Parvovirus.
Epstein-Barr Virus
Usually asymptomatic in early life.
o The older you are the more infectious it tends to be
Spread by saliva
Infectious mononucleosis (glandular fever)
Sub-Saharan Africa: Burkitt’s Lymphoma
HHV-6 and 7: Roseola Infantum
Also, known as exanthema subitum. Common between 6 months and 2 years of age. o Sudden onset of high fever. o Lasts few days then suddenly stops. o Followed by rash appearing.
Consequences of Chronic Hep B Infection
Cirrhosis.
Hepatocellular carcinoma.
Papillomavirus serotypes
Cause of cervical cancer.
Serotypes 16 and 18 = carcinogenic
Serotypes 6 and 11 = genital warts.
Cervarix vaccine
Gardasil quadrivalent vaccine
o For 6, 11, 16 and 18.
Adenovirus symptoms
URTI/pneumonia.
Conjunctivitis.
Diarrhoea
Parvovirus (Slapped Cheek)
Single-stranded DNA
P Antigen
• Attaches to P antigen.
o If lacking individual not susceptible.
• If P antigen: replicates in rapidly dividing cells (red cell precursors).
o Leads to aplastic crisis in people with haematological problems.
Newborns/Children
• Asymptomatic
• “Slapped cheek”
Adults
• Arthroplasty (adults)
• Fetal loss.
Important RNA Enveloped and Non-enveloped Viruses
Enveloped: MMR RSV, Influenza, Parainfluenza Hepatitis C HIV
Non-enveloped:
Rotavirus
Enteroviruses (polio)
Hepatitis A.
Measles Symptoms
1) Conjunctivitis
2) Couple of days: Koplik spots (inside the buccal mucosa).
3) 2 Days later: Rash (always starts behind the ears.
• Rare complication: Subacute Scleorising Pan-Encephalitis (SSPE)
o Present years later with neurodegenerative disease.
Rubella Symptoms
Fever, occipital lymphadenopathy
Mild rash.
Congenital Rubella - Triad of symptoms (EEH)
o Eyes: cataracts, micro-opthalmia, glaucoma
o Ears: sensineural deafness
o Heart: pulmonary artery stenosis, VSD
• Can also be more non-specific
o Low birth weight, rash, microcephaly.
Bronchiolitis
• Viral infection of infants (70% RSV, can also be Influenza, Parainfluenza).
• Inflammation of bronchioles.
• Cough, respiratory distress, wheeze.
• Can be severe in preterm
o Congenital heart disease.
o Try to prevent it with Palivizumab (monoclonal Ab) for prevention of RSV.
Rotavirus
Fever, vomiting, watery diarrhea.
Vaccines:
RotaTeq
RotaRix
Causes of Common Paediatric GI Symptoms: Abdominal Pain Chronic Vomiting/Haemetemesis: Chronic Diarrhoea: Failure to Thrive/Weight Loss Rectal Bleeding/Blood Stools
Abdominal Pain: • Constipation • Functional/RAP (recurrent abdominal pain)/IBS • Duodenal ulcers/Helicobacter Pylori • Inflammatory Bowel Disease
Chronic Vomiting/Haemetemesis:
• Gastro-oesophageal Reflux
• Intestinal Obstruction (if bile) intermittent.
• DU (rare).
Chronic Diarrhoea: • IBD o Weight loss o Abdominal pains o Tiredness o Rectal bleeding
Failure to Thrive/Weight Loss
• Coeliac
• Cystic Fibrosis
Rectal Bleeding/Blood Stools • IBD • Chron’s/UC • Fissures/haemorrhoids • Polyps/polyposis syndromes • Infection (bacterial).
Constipation Definition
Passing less than 3 stools per week OR painful bowel movements due to hard/large stools and stool retention in spite of passing >3 times per week
Organic disease causes of Constipation
- Hirschsprungs.
- Hypothyroidism.
- Neurologic.
- Anal stenosis.
Gastro-oesophageal Reflux treatment in infants
• Positioning • Thickening of feeds • Reduce acid o H2 antagonists o Proton pump inhibitors o Promotility agents (e.g. domperidone)
Eosinophillic Oesophagitis
Treatment resistant symptoms of GORD
Treatment • Dietary o Food exclusions o Pragmatic trials. • Oral budesonide • Monteleukast
Gastritis
Inflammation of the gastric mucosa
Due to infection with Helicobacter pylori.
Presentation • Vomiting • Abdominal pain • Haemetemesis • Anaemia.
Treatment:
Non-steroidal anti-inflammatories (NSAIDS)
C13 Breath Test
Used to detect H. pylori
If H. pylori is present, urea is metabolized to ammonia and C-labeled CO2
Treatment of H. pylori
2 weeks: amoxicillin, clarithromycin
+ 6/52 H2 antagonists OR PPIs
Repeat breath test/stool.
Chron’s Disease (IBD)
- Mouth to anus, patchy disease “skip lesions”
- Transmural inflammation
- Granulomas
Presentation
• Abdominal pain
• Weight loss
• Diarrhoea
• Insidious onset
• Growth failure
• Raised ESR/CRP/low albumin/Hb.
• Fever/clubbing/PR bleeding/oral ulcers/abdominal mass, other upper GI symptoms.
o Pyoderma gangrenosum - painful ulcers
Ulcerative Colitis (IBD)
Only rectum/colon
Continuous disease
Mucosal inflammation.
Presentation • Chronic bloody diarrhoea • Abdominal pain. • Weight loss. • Sclerosing Cholangitis • Arthropathy
Medical Treatment of Inflammatory Bowel Disease
Induce Remission • Exclusive enteral nutrition (Chron’s) o Reduce inflammation o Correct undernutrition o 6/52 of milk based formula • Steroids • 5-ASA • Biologicals (e.g. anti-TNF infliximab).
Maintain Remission
• 5-ASA (UC)
• Immunosuppressants
• Biologicals
