Total Topics :40

ENDOMETRIOSIS

The proliferation and functioning of endometrial tissue outside of the uterine cavity

Incidence: - 15-30% of all premenopausal women, -mean age at presentation: 25-30 years
 
Etiology - unknown

theories

- retrograde menstruation theory of Sampson
- Mullerian metaplasia theory of Meyer
- endometriosis results from the metaplastic transformation of peritoneal mesothelium under the influence of certain unidentified stimuli
- lymphatic spread theory of Halban
- surgical transplantation
- deficiency of immune surveillance


Predisposing Factors

- nulliparity
- age > 25 years
- family history
- obstructive anomalies of genital tract

Sites of Occurrence

ovaries  most common location, 60% of patients have ovarian involvement
broad ligament
peritoneal surface of the cul-de-sac (uterosacral ligaments)
rectosigmoid colon
appendix


Symptoms

there may be little correlation between the extent of disease and symptomatology

pelvic pain - due to swelling and bleeding of ectopic endometrium, unilateral if due to endometrioma

dysmenorrhea (secondary) - worsens with age, suprapubic and back pain often precede menstrual flow (24-48 hours) and continue throughout and after flow

infertility - 30-40% of patients with endometriosis will be infertile, 15-30% of those who are infertile will have endometriosis

dyspareunia  on deep penetration

premenstrual and postmenstrual spotting
bladder symptoms - frequency, dysuria, hematuria

bowel symptoms - direct and indirect involvement diarrhea, constipation, pain and hematochezia

Diagnosis

truly a surgical diagnosis

history - cyclic symptoms - pelvic pain, dysmenorrhea, dyschezia

physical examination

- tender nodularity of uterine ligaments and cul-de-sac
- fixed retroversion of uterus
- firm, fixed adnexal mass (endometrioma)

laparoscopy

- dark blue or brownish-black implants (mulberry spots) on the uterosacral ligaments, cul-de-sac, or anywhere in the pelvis
- chocolate cysts in the ovaries (endometrioma)
- powder-burn lesions
- early white lesions and blebs


Treatment

pseudopregnancy - cyclic estrogen-progesterone (OCP) or medroxyprogesterone (Provera)

pseudomenopause - danazol (Danocrine) = weak androgen, s/e:  weight gain, fluid retention, acne, or hirsutism, leuprolide (Lupron) = GnRH agonist (suppresses pituitary GnRH)

s/e: hot flashes, vaginal dryness, reduced libido, and osteoporosis with prolonged use .these can only be used short term because of osteoporotic potential

surgical

- laparoscopic resection and lasering of implants
- lysis of adhesions
- use of electrocautery
- unilateral salpingo-oophorectomy
- uterine suspension
- rarely total pelvic clean-out
- follow-up with 3 months of medical treatment

Alport’s Sd (most cases): "hereditary nephritis", type IV collagen deficit, mutation of COL4A5 ("colaas" - alpha-5 chain, type 4 collagen), hearing loss, ocular abnormalities (lens & cornea), hematuria since childhood (gross, micro)

Charcot Marie Tooth: loss of motor & sensory innervation, distal weakness & sensory loss, wasting in the legs, decreased deep tendon reflexes, tremor, foot deformity with a high arch is common (pes cavus), legs look like inverted champagne bottles. Most accurate test: electromyography. No tx.

Focal Dermal Hypoplasia: skin abnormalities and a wide variety of defects in eyes; teeth; and skeletal, urinary, gastrointestinal, cardiovascular, and central nervous systems.

Fragile X Syndrome: CGG trinucleotid repeat, FMR 1 gene mutation, mental retardation, large ears and jaw, post-pubertal macro-orchidism (males), attention deficit disorder (females)

Hypophosphatemic rickets: infants may show growth retardation, widened joint spaces and flaring at the knees at age 1 (> boys), bowing of the weight-bearing long bones, young children-dentition absent or delayed, older children-multiple dental abscesses.

Incontinentia pigmenti: skin abnormalities (blister--> warts--> hyperpigmentation--> hypopigmentation), alopecia, hypodontia, cerebral atrophy, slow motor development, mental retardation, seizures, skeletal & structural anomalies. Letal >males.

Orofaciodigital Sd: OFD1 gene mutation, malformations of face, oral cavity, digits with polycystic kidney disease and variable involvement of the central nervous system.

RETT’s Sd: sporadic mutation of MECP2 gene, onset 2yo, acquired microcephaly, stopped development, motor & speech regression, autism-like behavior, self-mutilating behavior, inconsolable crying/screaming fits, emotional inversion, hypotonia, dystonia, chorea, bruxism, scholiosis, long QT

Alport’s Sd: "hereditary nephritis", type IV collagen deficiency, alternating thickening & thinning of GBM, COL4A5 mutation, hearing loss, ocular abnormalities (lens & cornea), hematuria (gross or micro) since childhood.

Bruton’s Agammaglobulinemia: btk gene defect, no mature B cells or plasma cells, low lymphoid tissue, hepatitis, enterovirus infxs, first 6 months protected by maternal ab (no symptoms)

Becker’s Muscular Dystrophy: altered dystrophin gene, later onset than Duchene's, slow progression, relatively normal life span, less severe, rare cardiac involvement.

Chronic Granulomatose Disease (CGD): NAPDH oxidase deficiency, recurrent catalase (+) infxs, nitroblue tetrazolium test negative (yellow)

Congenital Aqueductus Stenosis: MCC of congenital obstructive hydrocephalus.

Color blindness (red-green): can't distinguish shades of red and green (usually blue-green)

Duchene’s muscular Dystrophy: dystrophin gene mutation (Xp21), absent dystrophyn protein, MC & severe of muscular dystrophies, normal until 5yo, short life span (<30yo), progressive muscle weakness, calf pseudohypertrophy, <3 failure, arrythmias, respiratory insufficiency and infxs (decreased mucociliary clearence). Pneumonias CC of death.

Fabry’s Disease: alpha Galactosidase A, Ceramide trihexose accumulation, angiokeratomas, renal failure, peripheral neuropathy.

Glucose 6-P Dehydrogenase (G6PD) Deficiency: chronic hemolytic anemia, MCC of enzymatic deficiency HA, Heinz bodies, bite cells. Triggers are infections, drugs (antimalarial), fava beans

Hemophilia A & B: factor VIII & IX deficiency respectively. PTT prolongation.

Hunter Disease: iduronate sulfatase deficiency, heparan sulfate accumulation, no corneal clouding, aggressive behaviour.

Inherited Nephrogenic Diabetes Insipidus: V2 receptors in collecting duct don't respond to ADH.

Lesch-Nyhan Sd: HGPRT1 deficiency, spastic cerebral palsy, self-mutilation, hyperuricemia, oral crystals in diapers, early death.

Menkes Disease: ATP7A gene mutation (copper efflux protein), Cu+ is lysil oxidase cofactor, Cu+ accumulates in intestine & kidneys; deficient in other tissues = deficient collagen cross linking; steely 'kinky' hair, MR, arterial tortuosity, hypotonia.

Ornithine Transcarbamoylase Deficiency: urea cycle, orotic aciduria + hyperammonemia (no megaloblastic anemia), orotic acid accumulation, increased glutamine . Cerebral edema, lethargy, vomiting, hyperventilation, convulsions, coma, death.

SCID: IL-receptor, Gamma chain deficiency

Wiskott Aldrich Sd: combined partial B & T immunodeficiency, IgM deficiency, thrombocytopenia, eczema.

Thalassemias are a heterogeneous group of hereditary blood disorders characterized by faulty globin chain synthesis resulting in defective hemoglobin, which can lead to anemia

Thalassemia provides partial resistance against malaria.

Beta thalassemia

- most commonly seen in people of Mediterranean descent

Etiology

usually due to point mutations in promoter sequences or splicing sites

β-globin locus - short arm of chromosome 11

In a normal cell, the β-globin chains are coded by a total of two alleles . Thus, there are two forms of the disease.

Beta thalassemia minor (trait): one defective allele

Beta thalassemia major (Cooley's anemia): two defective alleles

Pathophysiology

Inefficient erythropoiesis → anemia

Beta thalassemia minor and major: faulty β-globin chain synthesis → ↓ β-chains→ ↑ γ-,δ-chains → ↑ HbF  and ↑ HbA2

 

Alpha thalassemia

most commonly seen in people of Asian and African descent

Etiology

usually due to deletion of at least one out of the four existing alleles

Inheritance pattern: autosomal recessive

In a normal cell, the α-globin chains are coded by a total of four alleles. 

Thus, there are four forms of the disease. The severity of alpha thalassemia depends on the number of defective α-globin alleles.

- Silent carrier (minima form): one defective allele (-α/αα)

- Alpha thalassemia trait (minor form) -Two defective alleles ,Cis-deletion is common amongst Asian populations, whereas trans-deletions are more common in African populations

- Hemoglobin H disease: three defective alleles

- Hemoglobin Bart disease (major form): four defective alleles

Pathophysiology

Alpha thalassemia major (HbH disease) and Bart disease: faulty α-globin chain synthesis → ↓ α-chains → ↑ β-, γ-chains → ↑ HbH, ↑ Hb-Bart's