Buzzwords Flashcards
In the parasympathetic nervous system - the neurotransmitter of concern is ______ and it binds with ____ receptors
acethylcholine binds to nicotinic receptors on post ganglionic neurons and allows and influx of positive ions to go through
Acetylcholine binds to muscuranic receptors on the target organs which activates “G proteins”
Deficiency in C1 inhibitor leads to increases in ______.
Increased bradykinin and thus angiodema
SERPING1 gene is associated with _________
C1 inhibitor disease
Sensory and motor neuropathy, ataxia, retinal degeneration and haemolytic anaemia is associated with Vitamin __ deficiency?
Vitamin E deficiency
How do you calculate Stool Osmolarity?
Stool osmotic gap = Stool osmolality - 2(Stool Na + K)
Normally 50-100 = secretory
Osmotic diarrhea >100
Melanosis coli is pathognomonic for ______
Laxative abuse
Causes for osmotic diarrhea?
High osmotic gap (>100 mOsm/kg) causes of osmotic diarrhea include celiac sprue, chronic pancreatitis, lactase deficiency, lactulose, osmotic laxative use/abuse, and Whipple’s disease.
3 non-genetic causes for nephrogenic diabetes insipidus?
Obstructive uropathy, hypercalcaemia and lithium
Which phase of study evaluates efficacy, safety and dosing?
Phase II
What is the first phase of a study that looks at safety in a group less than 100?
Phase I
What are the anomalies seen in PHACES?
Posterior fossa malformation Haemangiomas - typically facial Arterial anomalies Coarctation + other cardiac defects Eye abnormalities
What eye anomalies are seen in PHACES?
Morning glory disc anomaly, glaucoma, cataracts, microphthalmia, optic nerve hypoplasia
Which syndrome?
An activating missense mutation in the GNAS1 gene encoding the α-subunit of GS, the G protein that stimulates cyclic adenosine monophosphate (cAMP) formation…
Mc-Cune Albright syndrome
In Mc-Cune Albright there is variability of clinical expression and the limited reliability of genetic testing from leukocyte DNA and unaffected tissues… why?
Because the mutation is postzygotic rather than genomic, it is expressed differently in different tissues (somatic mosaicism)
What are four extragonadal manifestations of Mc-Cune Albright syndrome?
- Thyroid: Hyperthyroid
- Adrenals: Cushing syndrome (excess cortisol)
- Growth hormone: gigantism or acromegaly
- Bones: Fibrous dysplasia of (usually) multiple bones
The main reason for rickets in Epidermal naevus syndrome, Raine syndrome, NF1, and McCune Albright - is due to excess secretion of FGF-23. What is the role of FGF-23?
FGF-23 is secreted by bones -> it decreases the reabsorption of phosphate and also suppress 1-alpha-hydroxylase, reducing its ability to activate vitamin D and subsequently impairing calcium absorption
_________ is is an X-linked proximal tubulopathy with characteristic abnormalities that include low-molecular-weight proteinuria, hypercalciuria, and other features of Fanconi syndrome.
They develop nephrocalcinosis, nephrolithiasis, progressive renal failure, and hypophosphatemic rickets
Dent Disease - CLCN5 gene
-> which encodes a renal Cl−/H+ antiporter
How do you differentiate a ‘dominant Bartter syndrome–like picture’ (also known as Bartter syndrome type V) vs classic Bartter syndrome
Mutations in an extracellular basolateral calcium-sensing receptor normally present in the loop of Henle.
Thus they present with suppressed parathyroid hormone function with hypocalcaemia, which differentiates them from patients with Bartter syndrome.
Which cytokines help turn a naive T cell into a TH2 helper cell?
IL-4, IL-5, IL-10
Also IL-13
Which interleukin helps switch B cells from IgM making to IgE making?
IL-4
TH2 cells also release ____ which stimulates production and activation of Eosinophils
IL-5
Give example of guanasine analogue?
Acyclovi
Examples of viral DNA polymerase inhibitors?
Cidofivir and Foscarnet
________ is a finding in the macula of the eye in a variety of lipid storage disorders and in central retinal artery occlusion
Cherry red spot
The cherry red spot is seen in central retinal artery occlusion, appearing several hours after the blockage of the retinal artery occurs. The cherry red spot is seen because the macula receives its blood supply from the choroid, supplied by the long and short posterior ciliary arteries
3 antipsychotic medication most related to weight gain?
Clozapine, Olanzapine, Quetipaine
Name the 2 most common gene defects seen in MODY?
1) Hepatocyte nuclear factor 1-alpha
2) Glucokinase gene defect
MODY Type 1 with HNF4α abnormality presents with ecreased levels of triglycerides, apolipoproteins AII and CIII (5–10% of MODY), neonatal hypoglycemia, very sensitive to _________
Sulfonyureas
MODY type 4 (HNF1a) - also responds to Sulfonyureas
Which MODY?
Decreased renal absorption of glucose and consequent glycosuria; most common type of MODY
MODY 3 - HNF1α anomaly
Which MODY?
Hyperglycemia of early onset (often neonatal diabetes) but mild and non-progressive; common
MODY 2 - glucokinase anomaly
Which MODY?
Renal malformations; associated with uterine abnormalities, hypospadias, joint laxity, and learning difficulties, pancreatic atrophy, pancreatic exocrine insufficiency; 5–10% of MODY
MODY5 - HNF1β
Which MODY?
Homozygous mutation causes pancreatic agenesis
MODY 4 - IPF1
__________ 1 is characterized by diabetes insipidus, DM, optic atrophy, and deafness—thus, the acronym DIDMOAD
Wolfram syndrome
Which syndrome?
The features include extreme insulin resistance, acanthosis nigricans, abnormalities of the teeth and nails, and pineal hyperplasia
Rabson-Mendenhall Syndrome
When do you use a fisher test versus chi squared test?
The type of test (formula) used for a hypothesis test depends on whether the data is dichotomous or continuous. For dichotomous data, use either a Fisher’s exact test or chi-squared test, with the former being used if there is a value <5 in one or more of cells in the data table.
When do you use a T-test vs Wilcoxon test?
For continuous data, when you compare two groups, either a t-test or a Wilcoxon signed rank test can be used, with the former used for normally distributed (parametric) data and the latter used for non-parametric data.
What is the half life of adenosine?
10 seconds
What is the recommended interval between IVIG (for Kawasaki) and immunisations?
11mo
Which anti-epileptic is contraindicated in juvenile myoclonic epilepsy?
Carbamazepine
PRRT2 gene is associated with …
Self-limiting and familial infantile seizures
SCN1A is associated with
Dravet syyndrome
GABRA1 is associated with —
Juvenile myoclonic epilepsy
Which syndrome?
1) Defective degranulation of neutrophils
2) Mild bleeding diathesis
3) Partial oculocutaneous albinism - light skin, silvery hair, photophobia
4) Progressive peripheral neuropathy
And tendency to cause HLH
Chediak Higashi Syndrome
Which syndrome?
Loss of function of LYST (for lysosomal traffic regulator), the gene mutated in CHS, is located at chromosome 1q2-q44.
Lead to indiscriminate interactions with lysosomal surface proteins, yielding giant granules through uncontrolled fusion of lysosomes with each other.
Chédiak-Higashi Syndrome
Which syndrome?
The diagnosis of this syndrome is established by finding large inclusions in all nucleated blood cells. These can be seen on Wright-stained blood films and are accentuated by a peroxidase stain. Because of impaired egress from the bone marrow, cells containing the large inclusions may be missed on peripheral blood smear but readily identified on bone marrow examination.
Chédiak-Higashi Syndrome
What sort of haematological anomaly is found in Chediak-Higashi syndrome?
Abnormal platelets? Raised PT? neutropenia?
Prolonged bleeding time
How can you treat Chédiak-Higashi Syndrome?
High-dose ascorbic acid may improve clinical status.
HSCT is the only treatment
Inverted T waves in lead V1 and VL are suggestive of….
Inferior MI
Which syndrome?
Autosomal dominant disorder
• Features can include: microcephaly, limb malformations, oesophageal and duodenal
atresias, and learning disability/mental retardation
• Hand and foot abnormalities may include hypoplastic thumbs, clinodactyly of second and
fifth fingers, syndactyly
toes), and shortened or absent middle phalanges
Feingold syndrome
How does Omalizumab work?
is a humanized monoclonal antibody (mAb) that binds IgE and prevents its binding to the high-affinity IgE receptor
How does Mepolizumab work?
An anti–IL-5 antibody that blocks IL-5-mediated eosinophilopoiesis, reduces severe asthma exacerbations and lowers sputum and blood eosinophils
Reduces need for OCS dose for adults
How does Dupilumab work?
An anti–IL-4 receptor antibody that inhibits both IL-4 and IL-13 production (both cytokines share the same IL-4 receptor) and atopic immune responses
Clinical studies do not support the routine use of allergen immunotherapy for…
food hypersensitivity, chronic urticaria and/or angioedema, latex allergy, or drug allergies
An inactivating mutation of the calcium sensing receptor produces…
hypercalcaemia or hypocalcaemia?
Hypercalcaemia
DRESS (Drug related Eosinophillic skin syndrome) It is classically seen ______ after initial exposure to an anticonvulsant (carbamazepine, phenobarbital, phenytoin, lamotrigine) or other drugs (allopurinol, minocycline, sulfonamides [dapsone, sulfasalazine.
When is DRESS seen?
What is the common triad?
DRESS is seen 2-6 weeks after initial exposure
Common triad: Rash, fever and hepatitis
DRESS syndrome is often distinguished from other medication reactions by its later onset following drug exposure and more persistent course.
Can get very sick with shock.
Late-onset thyroiditis and hypothyroidism may occur months later as a result of antimicrosomal antibodies directed against thyroid peroxidases involved in drug metabolism.
Malignant Hyperthermia-susceptible (MHS) individuals have skeletal muscle receptor abnormalities, most often in _______________, which allow excessive intracellular
calcium to accumulate in response to triggering agents
Ryanodine receptors (RYR1)
What are the immunodeficiencies seen with Ataxia Telengectasia?
The most frequent humoral immunologic abnormality is the selective absence of IgA, which occurs in 50–80% .
IgG2 or total IgG levels may be decreased, and specific antibody titers may be decreased or normal
What are characteristic features of Omenn syndrome?
Symptoms of GVHD
Other symptoms include eosinophilia, failure to thrive, swollen lymph nodes, swollen spleen, diarrhea, enlarged liver, low immunoglobulin levels
Causes of Madelung deformity can be remembered with the pneumonic:
HITDOC.
What is it?
Hurler syndrome Infection Trauma Dyschondrosteosis Osteochondroma Congenital e.g. Turner's syndrome
Heterozygous SHOX mutations cause _________________, a rare skeletal dysplasia that involves bilateral bowing of the forearms with dislocations of the ulna at the wrist and generalized short stature. Homozygous SHOX mutations cause the much more _____________
Heterozygous mutation - Leri-Weil dyschondrosteosis
Severe Langer mesomelic dwarfism.
(Autosomal dominant)
What is the pathological abnormality in achondroplasias?
Heterozygous mutations of genes encoding FGFR3 (fibroblast growth factor receptor 3) and PTHR1 (parathyroid hormone-1 receptor) result in disorders involving transmembrane receptors.
The mutations cause the receptors to become activated in the absence of physiologic ligands, which accentuates normal receptor function of negatively regulating bone growth. The mutations act by gain of negative function.
What is the inheritance pattern for achondroplasia?
Achondroplasia behaves as an autosomal dominant trait; most cases arise from a new mutation to average stature parents
Gene mutations in COMP results in …
Pseudoachondroplasia
Severe congenital neutropenia (SCN), also often known as _______ , is a group of rare disorders that affect myelopoiesis, causing a congenital form of neutropenia, usually without other physical malformations. SCN manifests in infancy with life-threatening bacterial infections
Kostmann syndrome
Presents in first few months of life
ELANE and HAX1 gene mutations
Pyoderma gangreonosum is associated with? (which IBD)
Ulcerative colitis
Erythema nodosum is associated with? (which IBD)
Crohns disease
Name some extraintestinal manifestations more common with Crohns disease?
Aphthous ulcers, peripheral arthritis, erythema nodosum, digital clubbing, episcleritis, renal stones (uric acid, oxalate), and gallstones
Note: Arthritis and episcleritis correlate well with disease activity
Name 5 extraintestinal manifestations more common with Ulcerative colitis?
1) Pyoderma gangrenosum
2) sclerosing cholangitis,
3) chronic active hepatitis,
4) and ankylosing spondylitis
Female with need to incontinence 5 minutes after urinating - what is this?
How do you manage?
Vaginal voiding due to labial adhesion
Sit on the toilet backwards and spread legs apart widely
Viral myositis commonly caused by which virus?
Influenzae B
Which syndrome with ptosis increases risk of JMML?
Noonan syndrome
Waardenburg syndrome is a syndrome with failure to have melanocyte migration. What are the four most common features?
Specific features for Type 3?
Specific features of Type 4?
1) Depigmented skin.
2) Deafness occurs in 9–37%
3) Heterochromia irides in 20%,
4) unibrow (synophrys)
Type 3 - + limb anomalies
Type 4 - + Hirschsprung disease
Where is erythropoetin produced?
Erythropoietin is produced by interstitial fibroblasts in the kidney in close association with the peritubular capillary and proximal convoluted tubule. It is also produced in perisinusoidal cells in the liver.
HLA B1502 is associated with….
Carbamazepine and TENS
HLA DR3 and DR7 associated with…
Graves disease
HLA DR4 and DR3 associated with…
Hashimoto
HLA DR3, DR8 and DR15 associated with…
SLE
Bone marrow with wrinkled tissue paper.
macrophages classic
Gaucher disease
Cherry red spot, no hepatosplenomegaly, vacuolated lymphocytes, severe neurodevelopmental delay in infancy, HEXA gene.
Tay Sachs
X- linked. Purine metabolism. Problems with motor function, growth, self injury, hyperuricaemia, cognitive impairment.
Lesch Nyan
