memory Flashcards
Where is stuff absorbed in gut?
- stomach
- duodenum
- jejunum
- ileum
- colon
Stomach:
- secretes: Gastric juices, Intrinsic factor
- absorb: Alcohol
Duodenum
- secretes: Pancreatic enzymes, bile salts
- absorbs: Amino acids, iron, calcium
Jejenum
- absorbs most things: sugars, amino acids, FFAs, calcium, vitamins (except B12)
Ileum
- absorbs: B12, IF, bile salts, water and electrolytes
Colon
- absorbs: Water, electrolytes and bile salts (small amounts)
NF-1 Clinical Manifestations and diagnosis
(diagnosed when any two of the following present) (incidence=1 in 4000)
1- Six or more cafe au lait macules. (Hall mark of NF and present in 100% of cases). Present at birth but increase in size, number and pigmentation especially during the first two years of life.
2- Axillary or inguinal freckling, multiple hyperpigmented areas 2-3mm in diameter
3- Two or more Lisch nodules which are hamartoma located within the iris. Present in 75% of NF-1, not a component of NF-2. Presenc increases with age
4- Two or more neurofibromas or one plexiform neurofibroma. Typically involve the skin, however can be situated along peripheral nerves and blood vessels. Small rubbery lesions with slight purplish discoloration of the overlying skin. Characteristicall appear during adolescence or pregnancy.
5- Distinctive osseous lesion such as a sphenoid dysplasia (which may cause pulsating exophthalmos) or cortical thinning of long bones
6- Opitc gliomas are present in 15% of patients.
7- First degree relative with NF-1. The majority of mutations in NF-1 occur in the paternal germ line.
Grades of VUR
VUR
• Grade I – reflux into non-dilated ureter
• Grade II – reflux into the renal pelvis and calyces without dilatation
• Grade III – mild/moderate dilatation of the ureter, renal pelvis and calyces with minimal blunting of the fornices
• Grade IV – dilation of the renal pelvis and calyces with moderate ureteral tortuosity
• Grade V – gross dilatation of the ureter, pelvis and calyces; ureteral tortuosity; loss of papillary impressions
Di George
- classic presentation
DiGeorge syndrome (DGS) is a constellation of signs and symptoms associated with defective development of the pharyngeal pouch system. The classical presentation for DGS is the triad of conotruncal cardiac anomalies, hypoplastic thymus (results in a range of T cell deficits), and hypocalcemia (resulting from parathyroid hypoplasia). Possible facial abnormalities include low set and posteriorly rotated ears, ocular hypertelorism, palatal anomalies, and tapered fingers. Approximately 90 percent of patients with DGS have heterozygous deletions in chromosome 22q11.2 (designated the DGSI locus), which occur spontaneously in most cases.
The most common cardiac defects account for two-thirds of cases and include the following:
• Interrupted aortic arch
• Tetralogy of Fallot
• Truncus arteriosus
• Atrial or ventricular septal defects
• Vascular rings
Smith-Lemli-Opitz Syndrome (SLOS)
- Multiple congenital anomalies and developmental delay caused by low plasma cholesterol and accumulated precursors
- AR
- Mutations 7-dehydrocholesterol-Δ7 reductase gene result in deficiency of the microsomal enzyme DHCR7, which is necessary to complete the final step in cholesterol synthesis.
- It is not known why defects in cholesterol synthesis result in congenital malformations, but as cholesterol is a major component of myelin and a contributor to signal transduction in the developing nervous system, neurodevelopment is severely impaired.
- The incidence of SLOS is estimated to be 1/20,000-60,000 births among whites
- Anomalies include: microcephaly, anteverted nares, retromicrognathia, low set ears, cleft palate, cataracts, syndactyly of toes 2-3, post-axial polydactyly, equinovarus deformity, genital anomalies including ambiguous genitalia, pre- and post-natal growth retardation, MR, cardiac defects (ASD, PDA, VSD), renal tract anomalies, adrenal insufficiency
- Spontaneous abortion of SLOS fetuses may occur.
- Type II SLOS often leads to death by the end of the neonatal period. Survival is unlikely when the plasma cholesterol level is <20 mg/dL
- Laboratory measurement should be performed by gas chromatography, as standard techniques for lipoprotein assay include measurement of cholesterol precursors, which may yield a false positive result
- Milder cases may not present until late childhood. Phenotypic variance ranges from microcephaly, cardiac and brain malformation, and multiple organ-system failure to only subtle dysmorphic features and mild developmental delay
- Treatment includes supplemental dietary cholesterol (egg yolk) and HMG CoA reductase inhibition to prevent the synthesis of toxic precursors proximal to the enzymatic block.
Marfan Syndrome Dx Criteria
Older criteria — Although there is variable phenotypic expression of MFS, aortic root dilatation and ectopia lentis are cardinal features of the disease and various systemic features support the diagnosis. Other symptoms and signs of MFS, such as joint hypermobility, are much more commonly seen in patients without the disease. Previous reliance on less specific features led to a tendency to over diagnose MFS in index cases or family members. As a result, stringent criteria for the diagnosis of MFS (Ghent nosology) were proposed in 1996. These criteria relied on the recognition of both “major” and “minor” clinical manifestations involving the skeletal, cardiovascular, and ocular systems, and the dura. Major criteria included: ectopia lentis, aortic root dilatation involving the sinuses of Valsalva or aortic dissection, and lumbosacral dural ectasia by CT or MRI, family or genetic history, and four of eight typical skeletal manifestations.
Limitations of some of the 1996 Ghent criteria included insufficient validation, inapplicability to children, and requirement of expensive and specialized evaluation [14].
Revised Ghent nosology — The 2010 revised Ghent nosology puts greater weight on aortic root aneurysm/dissection and ectopia lentis as the cardinal clinical features of MFS and on testing for mutations in FBN1 and other relevant genes [14]:
In the absence of family history of MFS, the presence of one of any of the following criteria is diagnostic for MFS:
• Aortic criterion (aortic diameter Z≥2 or aortic root dissection) and ectopia lentis*
• Aortic criterion (aortic diameter Z≥2 or aortic root dissection) and a causal FBN1 mutation as defined above
• Aortic criterion (aortic diameter Z≥2 or aortic root dissection) and a systemic score ≥7
• Ectopia lentis and a causal FBN1 mutation as defined above that has been identified in an individual with aortic aneurysm
In the presence of family history of MFS (as defined by the above criteria), the presence of one of any of the following criteria is diagnostic for MFS:
• Ectopia lentis
• Systemic score ≥7 points*
• Aortic criterion (aortic diameter Z≥2 above 20 years old, Z≥3 below 20 years, or aortic root dissection)*
Systemic score — The revised Ghent nosology includes the following scoring system for systemic features:
• Wrist AND thumb sign: 3 points (wrist OR thumb sign: 1 point)
• Pectus carinatum deformity: 2 (pectus excavatum or chest asymmetry: 1 point)
• Hindfoot deformity: 2 points (plain pes planus:1 point)
• Pneumothorax: 2 points
• Dural ectasia: 2 points
• Protrusio acetabuli: 2 points
• Reduced upper segment/lower segment ratio (US/LS) AND increased arm span/height AND no severe scoliosis: 1 point
• Scoliosis or thoracolumbar kyphosis: 1 point
• Reduced elbow extension (≤170 degrees with full extension): 1 point
• Facial features (at least 3 of the following 5 features: dolichocephaly [reduced cephalic index or head width/length ratio], enophthalmos, downslanting palpebral fissures, malar hypoplasia, retrognathia): 1 point
• Skin striae: 1 point
• Myopia >3 diopters: 1 point
• Mitral valve prolapse (all types): 1 point
A systemic score ≥7 indicates systemic involvement.
Calculation of serum osmolality and what is the normal range.
- Serum osmolality = 2 x (Na + K) + urea + glucose
- Normal serum osmolality is 275 – 295 mosm/L
Causes of DI and how to differentiate
- Central DI - ADH deficiency ie no ADH released from the hypothalamus. May be primary (eg septooptic dysplasia) or secondary (tumours eg cranipharyngioma, head injury, post-op, HIE, meningitis)
- Nephrogenic DI - ADH insensitivity at the kidney tubular cells. May be primary (genetic defect in ADH receptor/aquaporin gene) or secondary (PCKD, obstruction, lithium, hypokalemia/hypercalcemia)
Diagnosis:
- Urine osmolality of <700 mosm/L ( ie low urine osmolality = poorly concentrated urine = ADH would normally concentrate urine) in the presence of osmolality > 295 mosm/L
- water deprivation test:
1. have patient empty their bladder and then weigh accurately
2. record 96% of weight – this is as low as patient allowed to go
3. make sure patient has no access to water
4. weigh every 2 hours
5. measure serum electrolytres and osmolality and collect urine for osmolality - Urine osmolality < 700 mosm = DI - To differentiate between central and nephrogenic DI: give ADH (DDAVP) at this point and again fluid restrict – if the urine osmolality remains low then it is nephrogenic DI, if it rises it is central DI
Treatment
- Central DI: cornerstone is DDAVP IN. Effect lasts 8 – 10 hours (endogenous ADH lasts 1-3 hours). Allow child to return to mild polyuria before next dose (thus bd dosage)
- Nephrogenic DI: Ensure sufficient water intake to allow for large urine losses. Restrict sodium intake (this is because the kidney needs more water for greater solute loads – see above). Diuretics to reduce polyuria – eg thiazides, spironolactone + chlorothiazide
XLA
X-linked aggamaglobulinaemia (Brutons Tyrosine Kinase 80-90% of aggamaglobulinaemia)
Diagnosis
- Immunoglobulins very low or absent with no or very few circulating B-cells
- Pre-B cells present in bone marrow
- High percentage of T-cells, normal CD4:8 ratio
- Intestinal biopsy- absence of plasma cells
Clinical manifestation
- Otitis media, pneumonia, sinusitis, conjunctivitis, septic arthritis, osteomyelitis, septicaemia, meningitis,
- Pyogenic encapsulated organisms
- Onset 3-6 months when maternal IgG wanes
- Susceptibility to chronic enteroviral infection- encephalitis or dermatomyositis-like syndrome
- Absent lymph nodes/tonsils
Associated conditions
- Rheumatoid arthritis ~ 20%
- Lymphoreticular malignancy ~55%
- Sarcoid
Treatment- lifelong monthly IVIG (doesn’t prevent enterovirus) along with antibiotics
Transient hypogammaglobulinaemia
- Low IgG with recurrent viral/bacterial infections especially respiratory
- Delay of normal synthesis of immunoglobulins until after maternal IgG catabolised
- Resolution spontaneously by 4 years of age
- Specific antibody production normal
- Serious infections not significant problem
- Seen in relatives of patients with SCID
- Males 60%
- Associated with atopy
- Management- antibiotic prophylaxis, rarely IVIG
Peutz-Jeger Syndrome
Peutz Jeghers polyps – mostly as part of Peutz-Jegher’s syndrome…
Characteristics – Mucocutaneous pigmentation, intestinal polyposis and increased risk of GIT malignancy
Genetics – AD with high penetrance however 50% have no FHx – suggesting a high spontaneous mutation rate
Clinical features
Pigmentation - Blue-grey/brownish spots on the lips, buccal mucosa and perioral region, also sometimes seen on the fingers and toes, appear in infancy and early childhood and then fade as an adult, may become CLUBBED
Polyposis – hamartomas, usually multiple, stomach, small bowel (proximal>distal), colon, in themselves are NOT premalignant, increased risk of intussusception (lead-point), often lead to iron deficiency anaemia
Malignancy
- GIT tumours (15%) – Adenomas, adenocarcinomas
- Extra GIT tumours (35%) – lung, thyroid, gall bladder and biliary tree, breast, pancreas, cervix, ovary and sertoli testicular tumours
Management
- Careful surveillance
- Counseling and surveillance of siblings and children
Neonatal lupus
Transplacental transfer of maternal IgG antibodies.
Tranisent skin rash (pink macules & papules) – anti-La antibodies
Permanent complete heart block – antiRo antibodies
Periodic Fever syndromes
• Disorders of immune excess resulting in failure of regulation of immune cells.
• Hereditary periodic fever syndromes - a group of hereditary disorders with similar clinical features of recurrent short episodes of fever associated with inflammatory manifestations
o Usually self-limited in nature and occur in the absence of infection or autoimmune reaction
o Each of the disorders has a distinct genetic defect
o Most of these proteins are members of the Death Domain superfamily and are involved in inflammation and apoptosis. These proteins mediate the regulation of nuclear factor-kB (NF-kB), cell apoptosis, and interleukin 1β secretion through cross-regulated and common signaling pathways.
• The most common hereditary disorder is familial Mediterranean fever (FMF), followed by tumor necrosis factor (TNF)–receptor-associated periodic syndrome (TRAPS), and hyperimmunoglobulinemia D syndrome (HIDS).
• Secondary amyloidosis (AA) was reported as a complication in all of these disorders. FMF and HIDS are autosomal recessive diseases, whereas TRAPS and MWS/FCU/CINCA are autosomal dominant diseases.
• PFAPA is another periodic fever syndrome : periodic fever, adenopathy, and pharyngitis with aphthous ulcerations.
Familial Mediterranean Fever
- Most common of periodic fever syndromes
- Autosomal recessive
- Characterized by brief, acute, self-limited episodes of fever and polyserositis recurring at irregular intervals, as well as development of amyloidosis
- Mutation in the MEFV gene encoding the protein pyrin, one function of which is regulation of the production of interleukin-1 beta
Periodic fever with aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome
• Characterized by febrile episodes beginning in early childhood that recur approximately every three to four weeks and are associated with typical clinical features in the absence of other cause.
• Episodes are abrupt in onset, last three to five days, and are accompanied by one or more of the following:
o Pharyngitis (exudative or nonexudative)
o Mild aphthous ulcerations
o Lymphadenopathy
o Chills (rigors) / Fatigue / Headache /Mild abdominal pain
• Leukocytosis and elevation of inflammatory markers occur acutely during episodes and return to normal between episodes, when patients are vigorous and grow normally. Most patients with PFAPA outgrow the febrile episodes with time, and no long-term consequences have been identified.
• The majority of patients respond dramatically to a single dose of prednisone/ bethamethasone with prompt resolution of symptoms within 24 hr
• Complete resolution has also been reported after tonsillectomy.
• Affected children grow normally and have spontaneous resolution within 4–8 yr with no long-term sequelae.
