Clinical vignettes Flashcards
common manifestations of von Hippel-Lindau disease
Hemangioblastoma (CNS or retinal andiomas), Renal cell carcinoma, Pheochromocytoma (catecholamine secreting tumors from adrenals), multiple tumors often seen in a single organ
VHL and Hif 1-alpha
protein VHL is part of a multi-protein complex targeting select proteins such as Hypoxiainducible factor (Hif)-alpha for degradation via ubiquitylation. Usually it is regulated by oxygen levels (degraded with normoxia, not with hypoxia). Dysfunctional VHL = increased Hif-alpha triggering production of vascular promoting factors (ie vascular endothelial growth factor VEGF and platelet derived growth factor PDGF)
VHL sporatically mutated in many renal cel carcinoma
60-70% of sporadic clear-cell kidner cancer have inactivation of both VHL alleles, may be by mutation or hyper-methylation of promoter (ie not inherited)
renal cell carcinoma treatment
Sunitinib and Sorafenic are VEGFR tyrosine kinase inhibitors. VEGFR (key in developing new blood vessels). Developed based on pathophysiology of VHL
Li-Fraumeni Syndrome
autosomally dominant hereditary cancer associate with mutation of p53 (~70%). Typical LFS cancers include sarcoma, breast cancer, brain tumor, adrenal cortical tumor, or leukemia
classifying hereditary cancer syndrome as Li-Fraumeni
proband with sarcoma dianosed before age 45, first-degree relative with any cancer under age 45, and first- or second-degree relative with any cancer under age 45 or a sarcoma at any age
classifying Li-Fraumeni like syndrom
proband with any childhood cancer or sarcoma, brain tumor or adrenal cortical tumor dianosed before age 45, first or second degree relative with a typical LFS cancer at any age, and a first or second degree relative with any cancer under age 60
testing for LFS and LFL
check p53 hotspots for mutations (exons 5-9), sequence entire p53 mRNA, if no detectable mutation move on to other genes such as hChk2 or PTEN
Multiple Sclerosis
Common CNS disease causes by inflammitory demyelination of nerves, leading to decreased conduction speed and sultiple lesions on the CNS. Symptoms include fatigue, walking impairment, spasticity, cognitive impairment, bladder dysfuntion, pain, mood instability, and sexual dysfunction.
mechanism of nerve conduction
Electrical conduction along nerve fibers via action potentials. Cells depolarize causing the next ion channels in the chain to open up, neurotransmitters are released and message reaches its destination. Improved by myelination of nerves
consequences of demyelination
Neuronal damage, slower conduction of action potentials, proliferation of sodium channels along axon, and symptoms of MS.
therapies improving nerve function
Na channel blockers phenytoin and flecainide preserve axons, K channel blockade enhances conduction of action potentials in demyelinated axons through inhibition of K channels
Straight forward DKA
Polyuria, Polysipsia, and weight loss (suspicious of diabetes) check glucose. Rapid deep breathing, nausea and vomiting (suspicious for ketoacidosis, check pH and HCO3-)
metabolic disturbances of DKA
dehydration due to hyperglycemia, high blood glucose (normal 70-120, DKA can be around 580), venous pH is low (below 7.28. close to ~7.0), bicarbonate is low due to rapid breathing (below 18, can be close to 5), K+ is high in blood and low in cells due to retention of Na+ to combat dehydration(above 4.5, maybe 5.8)
stimulus for insulin release
regulated by glucose sensing system with the beta cells of the pancreas. Insulin stimulates uptake of glucose and triglycerides while promoting synthesis of fats, proteins, and glycogen and inhibiting the reverse processes
