Stuff I've Missed :) Flashcards
(46 cards)
Arsenic Poisoning
MoA: Binds to sulfhydryl groups and disrupts cellular respiration & gluconeogenesis
inhibits pyruvate dehydrogenase
Sources: pesticides, insecticides
contaminated water (wells)
pressure-treated wood
Manifestations: garlic breath, vomiting, watery diarrhea, QTc prolongation ACUTE
hypo/hyperpigmentation, hyperkeratosis, stocking-glove neuropathy CHRONIC
Tx: DIMERCAPROL or DMSA
Parvovirus B19 and Erythema Infectiosum
single-stranded DNA virus
causes: malaise, congestion, headache, fever that is followed by an erythmatous rash on the cheeks (“slapped cheek”)
A lacy reticular rash follows, spreading over trunk and extremities
Parvovirus B19 replicates in erythrocyte precursors in bone marrow
Clonidine
Used in Tx of severe or refractory HTN
MoA: exerts effects on HR and BP by stimulating presynaptic alpha-2 adrenergic receptors in rostral ventrolateral medulla
-> results in decrease in presynaptic release of NE and decreased sympathetic outflow causing both BRADYcardia and a decrease in PVC
HER2 (ERBB2)
overexpressed in 20%-30% of breast cancers
HER2 is a transmembrane glycoprotein with TYROSINE KINASE activity that active to INCREASE cell proliferation
in breast cancer, HER2 overepxression is associated with poorly differentiated rapidly growing tumors
HPV and SCC
HPV produces oncoproteins E6 and E7
E6 –> binds to p53, tumor supressor that normally inhibits proliferation of cells with genetic abnormalities
–> causes ubiquination of p53 which induces its degradation
E7 –> binds to RB protein which results in displacement of E2F – promoting unregulated DNA replication and cyclin-mediated cell cycling
Alternative RNA Splicing
Process where exons of a gene are reconnected in multiple ways during post-transcriptional processing
Creates different mRNA sequences and different protein forms –> normal phenomenon in eukaryotes that greatly increases the biodiversity of proteins encoded by the genome
Rett Syndrome
X-linked recessive
Affects females (males die in utero)
presents in early childhood with progressive neurodegeneration and stereotypical hand movements
Alkaptonuria
Autosomal Recessive
Deficiency of homogentisic Acid Dioxygenase – enzyme involved in tyrosine metabolsim
Excess homogentisic acid causes diffuse blue-black deposits in connective tissues
Adults – sclerae and ear cartilage hyperpigmentation along with osteoarthropathy of the spine and large joints
Homocystinuria
Due to autosomal recessive mutation causing cystathionine synthase deficiency
Clinically: optic lens dislocation, intellectual disability, marfanoid habitus, thromboembolic complications
Dx: INCREASED plasma and urinary homocystine levels
Tx: Pyridoxine (B6) administration
dietary methionine restriction and cysteine supplementation
Homeobox Genes
highly conserved DNA sequence that is usually about 180 nucleotides long
These genes typically code for TRANSCRIPTION FACTORS that bind to regulatory regions on DNA – alter expression of genes involved in the segmental organization of the embryo
encode DNA-binding transcription factors that play an important role in segmental organization of the embryo along the cranio-caudal axis
Thoracic Outlet Syndrome
most commonly occurs due to compression of the brachial plexus within the scalene triangle which is formed by the anterior and middle scalenes and first rib
Shiga and Shiga-like toxin
inactivate the 60s ribosomal subunit in human cells, leading to an inhibition of protein synthesis and eventual cell death
RB protein
regulator of the G1/S checkpoint
active form (dephosphorylated) and inactive (phosphorylated) forms
when phosphorylated, it is inactive and will allow cells to progress from G1/S to S
When dephosphorylated, it is active and will stop the cell from dividing – allows cell to enter a quiescent phase (G0)
Fibular neck injury
The common peroneal nerve is the most frequently injured nerve in the leg due to its superficial location as it courses laterally around the neck of the fibula
Injury to common peroneal nerve –> loss of dorsal foot sensation as well as impaired dorsiflexion and eversion resulting in foot drop
Heteroplasmy
Responsible for the variability in presentation of mitochondrial diseases
some cells will contain mitochondria w/ mostly damaged mtDNA
some cells will contain mitochondria with mostly normal mtDNA
Hereditary Nonpolyposis Colon Cancer (HNPCC) or Lynch Syndrome
autosomal dominant
colon cancer at a young age (<50) – family history reveals high incidence of colon cancer and extraintestinal (e.g. endometrial) cancers in first-degree relatives
Inherited mutation in genes responsible for DNA mismatch repair – MSH2 and MLH1 primarily
Pyruvate Dehydrogenase Complex
Mitochondrial enzyme complex linking glycolysis and TCA cycle
Contains 3 enzymes requiring 5 cofactors:
1) Thiamine (B1)
2) Lipoic Acid
3) CoA (B5, pantothenic acid)
4) FAD (B2, riboflavin)
5) NAD+ (B3, Niacin)
Activated by: INCREASED NAD+/NADH ratio, INCREASED ADP, INCREASED Ca2+
cofactor mnemonic: The Lovely Coenzyme For Nerds
Pyruvate Dehydrogenase Complex Deficiency
Causes buildup of pyruvate that gets shunted to lactate (via LDH) and alanine (via ALT), X-linked
Findings: neurologic defects, lactic acidosis, increased serum alanine starting in infancy
Tx: increased intake of ketogenic nutrients (eg, high fat content or increased lysine and leucine)
Ornithine Transcarbamylase Deficiency
Most common urea cycle disorder
X-linked Recessive
interferes with body’s ability to eliminate ammonia – often evident in first few days of life
Excess carbamoyl phosphate is converted to orotic acid (part of pyrimidine synthesis pathway)
Findings: increased orotic acid in blood and urine, decreased BUN, symptoms of hyperammonemia
NO megaloblastic anemia
Abetalipoproteinemia
Autosomal Recessive
Mutation in gene that encodes microsomal transfer protein (MTP) –> Chylomicrons, VLDL, LDL absent
Deficiency in ApoB-48, ApoB-100
Affected infants: present with severe fat malabsorption, steatorrhea, failure to thrive
Later manifestations include retinitis pigmentosa, spinocerebellar degeneration due to vitamin E deficiency, progressive ataxia, acanthocytosis
Intestinal biopsy shows lipid-laden enterocytes
Tx: restriction of long-chain fatty acids, large doses of oral Vitamin E
Alcohol-based Disinfectants
Kill vegetative bacteria (not spores), fungus, and envoloped viruses by dissolving their lipid bilayer membranes and subsequently denaturing their proteins
(nonenveloped viruses such as: adenovirus, rhinovirus, enterovirus, and poliovirus are less susceptible)
Benign Prostatic Hyperplasia Tx
5-alpha reductase inhibitors (eg, finasterid, dutasteride) block the conversion of testosterone to dihydrotestosterone in the prostate
these drugs reduce the prostate volume in pt’s with BPH and relieve the fixed component of bladder outlet obstruction
PDE5 Inhibitors
Sildenafil, tadalafil
first-line agents for treatment of erectile dysfunction – PDE5 inhibitors increases activity of cGMP leading to greater and more prolonged tumescence in men with ED
Can also inhibit PDE6 in retina – pt’s experience a bluish discoloration to vision
Trisomy 18 (Edward’s Syndrome)
features: micrognathia, low-set ears, prominent occiput, rocker bottom feet
- significant hypertonia: clenched hands and overlapping fingers
- cardiac anomalies (VSD, PDA), genitourinary (horseshoe kidney), and GI (meckel’s diverticulum, malrotation)
prenatal US in utero shows fetal growth restriction
