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Tryptase can be used as a marker for?
Mast cell degranulation
What produces calcitonin?
C cells of the thyroid gland
What type of hypersenstitivity is Anaphylaxis and describe its presentation.
- Type 1 hypersensitivity- mast cell degranulation and histamine release
- ⇩blood pressure
- ⇧ Heart rate
- Shortness of breath
- Skin rash e.g uticaria/hives
Degranulation of mast cells is accomplished by what?
CROSS-LINKING of multiple membrane-bound IgE antibodies by a specific antigen, resulting in IgE-Fc receptor aggregation on the cell surface.
How do you calculate Filtration fraction?
FF= GFR/ RPF
What are the effects of vasoconstriction of the efferent arteriole on GFR, RPF and FF? Explain the mechanism behind it.
As RPF decreases, the slower capillary flow allows more time for filtraton of plasma= ⇧FF
- GFR: ↑
- FF: ↑
- Efferent arteriole constriction causes ⇧ pressure in glomerular capillaries due to decreased outflow= ⇧GFR
- Constriction causes ⇩RPF
Where is the superior gluteal nerve derived from?
Where is a safest site for intraglueal injections?
- Anterolateral gluteal region Von Hochstetter triangle
Where is the sciatic nerve derived from?
Which nerves does the sciatic nerve split into?
Common peroneal and Tibial nerves
What does the sciatic nerve innervate?
Posterior thigh, knee flexors (hamstrings), all leg and foot muscles.
What can cause injury to the sciatic nerve?
Injections into the posterior thigh
What is positive predictive value?
Probability that person actually has the disease given a positive test result.
The probability that person actually has the disease given a positive test result is known as?
Positive predictive value
What is the relationship between prevalence and positive predictive value?
As disease prevalence increases, the PPV will also increase due to a high proportion of true positives.
What is positive likelihood ratio? How do we calculate?
- A ratio representing the likelihood of having the disease given a positive result.
- = Sensitivity/ 1- Specificity
A ratio representing the likelihood of having the disease given a positive result is known as?
Positive likelihood ratio
What is negative likelihood ratio? How do we calculate?
- A ratio representing the likelihood of having the disease given a negative result.
- = 1- Sensitivity/ Specificity
A ratio representing the likelihood of having the disease given a negative result.
Negative likelihood ratio
Describe the levels of these hormones (estrogen, LH, FSH) in Turner syndrome.
Which cardiovascular malformations are associated with Turner's syndrome?
- PREDUCTAL coartation of the aorta
- BICUSPID AORTIC VALVE
- Aortic dissection
Lymphedema in a neonate is suggestive of?
Describe the physical presentation of Turner's syndrome.
- Short stature
- Shield chest: broad, with widely spaced nipples
- Cystic hygroma/ Webbed neck: broad neck with low hairline
What is vaginal adenosis and who are at risk of developing it?
- Replacement of the vaginal squamous epithelium with glandular columnar epithelium.
- It occurs in female children of women exposed to Diethylstillbestrol during pregnancy.
- Vaginal adenosis is a precursor of clear cell adenocarcinoma of the vagina.
What abnormality is seen in female children of women exposed to diethylstillbestrol (DES) during pregnancy?
- Vaginal clear cell adenocarcinoma
- Congenital Mullerian anomalities
Congenital mullerian anomalities is associated with the use of which teratogen?
Small, underdeveloped ovaries that consist of connective tissue with no follicles present are characteristic of?
- Turner's syndrome
- Streak ovaries
The cytogenic defect t(15;17) is associated with?
Acute promyelocytic leukemia (AML type M3)
Describe the translocation abnormality assocated with Acute promyelocytic leukemia (AML type M3).
- t (15; 17)
- The gene for retinoic acid receptor alpha from chromosome 17 is transferred to chromosome 15 in a location adjactent to the PML (promyelocytic leukemia) gene.
- ⇛ Coding for an abnormal retinoic acid receptor
In this disease, there is an abnormal retinoic acid receptor.
Acute promyelocytic leukemia (AML type M3)
Mutations of the genes that code for the epidermal growth factor receptors are associated with?
- erbB1- Non-small cell lung carcinoma
- erbB2/ HER2/neu- Breast cancer, ovary gastric carcinomas
erb1B1 is associated with which tumor?
non-small cell lung carcinoma
erbB2 is associated with which tumor?
Breast, ovarian, gastric carcinoma
Defective platelet derived growth factor receptor plays a role in the pathogenesis of?
Chronic myelomonocytic leukemia (CMML)
What is the best way to prevent neonatal tetanus?
Vaccinate pregnant women with the tetanus toxoid, to allow transfer of protective IgG antitoxin antibodies across the placenta to the fetus.
What is Hepcidin? What is its function?
An acute phase reactant synthesized by the liver that promotes intracellular storage of iron
Acetylcholine release from the presynaptic terminal vesicles at the neuromuscular junction depends on?
The influx of extracellular calcium into the presynaptic terminal.
What are the effects of muscarinic agonists on blood vessels?
- Binding of muscarinic receptors on endothelial cells promote release of nitric oxide, also called endothelium-derived relaxing factor.
- NO activates cGMP which causes calcium efflux from the cells.
What is the function of ferroportin?
Transfers intracellular iron into the circulation (blood) from macrophages and enterocytes.
How does Hepcidin influence body iron storage?
- Hepcidin interacts with FERROPORTIN - a transmembrane protein located on enterocytes and macrophages.
- It degrades ferroprotein, decreasing intestinal iron absorption and inhibiting the release of iron by macrophages.
What facilitates iron absorption from the small intestine?
Divalent metal transporter (DMT-1)
What is the function of divalent metal transporter 1?
Facilitates iron absorption from the small intestine.
What increases the synthesis of hepcidin?
High iron levels and inflammatory conditions
What decreases the synthesis of hepcidin?
Hypoxia and increased erythropoiesis
What are the effects of low hepcidin levels?
Increase intestinal iron absorption and stimulate iron release by macrophages.
What is the MOA of Celecoxib?
Reversibly inhibits specifically the cyclooxygenase (COX) isoform 2
This drug inhibits cyclooxygenase (COZ) isoform 2.
What are the side effects of COX 2 inhibition?
- COX 2 plays a role in the production of prostacyclin (PGI2), a substance that promotes anticoagulation and vascular dilation.
- Inhibiting COX 2 increases the risk of clotting and THROMBOSIS.
What is the function of PGI2?
- Anticoagulant- ⇓ platelet aggregation
- Vascular dilation
What are the effects of selective COX 2 inhibitors on platelet function?
They do not impair platelet function because platelets predominantly express COX 1.
What is GABA also known as?
How is GABA ( y-aminobutyric acid) synthesized?
GABA is synthesized from Glutamate, and this is mediated by glutamate decarboxylase with the use of B6 (pyridoxal phosphate) as a cofactor.
What breaks down /catabolize GABA?
What is the location, structure and effect of stimulation of GABAA receptors?
- Location: Brain
- Structure: Ion channel
- Effect of stimulation: Cl- influx
What is the mechanism of Benzodiazepines?
- Allosterically binds to the GABAA receptor and stimulates the influx of chloride ions into the neurons (⇧frequency of Cl- channel opening).
- Thus they facilitate the inhibitory action of GABA in the CNS.
What are the stages of Pagets disease?
- 1. Osteolytic phase - OSTEOCLAST dominate; (excessive RANK signalling and NF-kB activation)
- 2. Mixed phase- OSTEOCLASTS and OSTEOBLASTS.
- 3. Osteosclerotic phase- OSTEOBLASTS dominate
- 4. Quiescent phase- minimal osteoclastic/osteoblastic activity
Mosaic pattern of lamellar bone is diagnostic of?
PAgets disease of the bone
Patients with Pagent's disease are at increased risk of developing?
What is the initial abnormality in pagets disease of the bone?
Initially there is an increase in the number and activity of osteoclasts, followed by increased osteoblastic activity and bony overgrowth.
What is the mechanism of Amiodarone?
- Class III antiarrythmic
- Block K+ channels and inhibit the outward K+ currents during phase 3 of the cardiac action potential, prolonging repolarization and duration of the action potential.
What are the Class III antiarrythmics?
What is the risk of Amiodarone causing torsades de pointes?
Very little risk
Polymorphic ventricular tachycardia is characteristic of?
Torsades de pointes
What is the pathology seen below?
Torsades de pointes
What is nonhomologous end joining and in which disease is it mutated?
- Brings together 2 ends of DNA fragments to repair double stranded breaks.
- Mutated in Ataxia telangiectasia and Fanconi anemia
The bringing together of 2 ends of DNA fragments to repair double stranded breaks is known as?
nonhomologous end joining
What is the defect in Ataxia telangiectasia?
Defect in the ATM gene which is responsible for DNA beak repair
Describe the presentation of Ataxia telangiectasia.
- Ataxia: Unsteady gait, loss of balance
- Cerebellar ataxia: Underdeveloped language skills, eyes and head do not move in synch when looking at objects.
- Telangiectasia: Superficial blanching nests of distended capillaries.
What is bare lymphocyte syndrome?
Defect in expression of HLA class II antigens on the surface of APCs
Defect in the expression of HLA clas II antigens on the surfaces of APCs is characteristic of?
Bare lymphocyte syndrome
What are the effects of Thromboxane?
- Increases platelet aggregation
What are Kluchitsky cells?
- a.k.a Enterochromaffin cells
- Located in the gut, it synthesizes serotonin, where it plays a role in peristalsis and nausea.
Neoplasm of Kluchitsky cells are diagnostic of?
Small cell (oat cell) carcinoma
What is Hageman factor?
- Factor 12 of the clotting cascade
- It is activated by collagen exposed when the vascular basement membrane is damaged.
What is the function of Kallikrein?
Converts High molecular weigh kininogen (HMWK) to Bradykinin
Describe the path of CSF flow.
Lateral ventricles ⇒ interventricualar foramen of Monro ⇒ 3rd ventricle ⇒ cerebral aqueduct ⇒ 4th ventricle ⇒ foramina of Luschka and Magendie ⇒ Subarachnoid space.
What secretes CSF?
Choroid plexus in lateral and 4th ventricles
What reabsorbs CSF?
What causes a Communicating hydrocephalus?
⇩CSF absorption by arachnoid granulations/ villi.
Ususally due to meningeal infections or subarachnoid/ intraventricular hemorrage.
What causes a Noncommunicating hydrocephalus?
- Caused by structural blockage of CSF circulation within the ventricular system.
- E.g. Aqueduct of Sylvius, Colloid cyst blocking foramen of Monro, Arnold Chiari, Dandy walker
This disorder is caused by decreased CSF absorption by the arachnoid granulations/ villi.
This disorder is caused by a structural blockade of CSF circulation within the ventricular system.