UWSA1 Non Advanced Editor Flashcards
What does CFTR do in eccrine sweat glands? What happens when it is defective?
Normally acts to reabsorb Cl- from sweat and also enhances sodium reabsorption by epithelial sodium channel (ENaC).
-mutated CFTR diminishes salt reabsorption and increases sweat tonicity due to higher levels of sodium and chloride.
What is the normal effect of CFTR channel in the respiratory epithelium? What happens when it is mutated?
Normally secretes Cl- into the lumen and has an inhibitory effect on the ENaC, decreasing luminal sodium absorption.
-mutated CFTR reduces luminal Cl- secrtion and increases luminal sodium absorption, depleting the water content of the surface fluid layer overlying the mucosal cells. This contributes to the production of thick, viscid secretions that are low in both sodium and chloride
Three patients have mutations in 3 different exons of the same genetic locus, but all have Beta-Thalassemia; what is this?
Allelic heterogeneity
-note that duchenne and becker are also examples of allelic heterogeneity. Both caused by mutations in the dystrophin gene, but their presentations are slightly different.
What is variable expressivity?
Refers to the degree of variation in phenotype between different individuals w/ the same gene mutation. Good example would be CF patients homozygous for delta508 CFTR muation
What are the cysteinyl-containing leukotrienes and what role do they play in asthma?
Leukotriene C4, D4, and E4
They are synthesized and released by eosinophils and mast cells. Play a role by inducing bronchospasm, bronchial mucus secretion, and bronchial edema.
What are the likely endocrine manifestations of hereditary hemochromatosis?
Diabetes mellitus, secondary hypogonadism, and hypothyroidism
-DM is secondary to pancreatic islet destruction
Which infections is someone w/ hereditary hemochromatosis especially susceptible to?
Listeria, Vibrio vulnificus, and Yersinia entercolitica
This is because these organisms need iron to grow and thus have increased virulence with increased iron
Why can portal hypertension cause retrograde flow into splenic vein causing congestion of splenic red pulp/splenomegaly?
Portal venous system is valveless
If the minimal inhibitory concentration of ciprofloxacin is reduced with a high pH agar, what does that indicate as the source of antibiotic resistance?
MDR efflux pump
COL1A1 gene mutation
Osteogenesis imperfecta
Fragile-X is caused by a trinucleotide repeat expansion in which gene? What is the repeat? Inheritance pattern?
CGG repeat in FMR1 gene, X-linked DOMINANT meaning mothers transmit to 50% of both genders of kids, and fathers transmit to all daughters but NO sons
Patient has recurrent infections, abnormal gene that codes for a cytoplasmic tyrosine kinase. Normally, this tyrosine kinase is activated in CD-19 positve cells by antigen exposure, resulting in cell maturation. What is disease and inheritance pattern
Bruton agammaglobulinemia (X-linked agammaglobulinemia). Bruton’s tyrosine kinase is important to maturation of B cells; without it they cant leave the bone marrow
Proteins destined for the endoplasmic reticulum possess what signal sequence? What happens to their interaction with SRPs if there is a mutation? Where would they build up?
N-terminal peptide signal sequences are translated in cytosol and recognized by Signal Recognition Particles, which halt translation and target the ribosome to protein pores in rough ER. If the N-terminal peptide signal is messed up, then SRP wont bind, and peptides will be stuck in cytosol
Maple syrup urine disease is characterized by a defect in alpha-ketoacid dehydrogenase. What is the cofactor for this enzyme?
Thiamine
What would the peripheral smear of someone with alpha-thalassemia minor (loss of 2 alpha chains) look like?
Hypochromic and microcytic as a result of imbalaned globin chain production resulting in decreased total hemoglobin in red cells
What is the purpose of androgen binding protein, and what cells make them?
- high concentrations of testosterone relative to circulation must be maintained in seminiferous tubules and epididymis for spermatogenesis to occur.
- done by ABP, which is made by Sertoli cells in response to FSH. ABP makes hormones less lipophilic, reducing diffusion out of luminal fluid
How does Glucagon interact with hepatocytes?
Binds to GPCRs, activating Gs, which stimulates adenylate cyclase to ^ cAMP. cAMP activates protein kinase A, which activates key enzymes in:
- glycogenolysis (glycogen phosphorylase, phosphorylase kinase)
- gluconeogenesis (pyruvate carboxylase, phosphoenolpyruvate carboxykinase)
Sweating is mediated by cholinergic POSTganglionic fibers of the SYMPATHETIC nervous system. How is refractory axillary hyperhydrosis treated?
Ablation of the thoracic sympathetic trunk at the T2 segment
What is hyaline cartilage made out of?
Histologically characterized by dispersed chorndrocytes in a matrix of type II collagen and proteoglycans. Blood vessels are absent, and articular cartilage lacks a perichondrium.
What are some findings of advanced osteoarthritis?
Apoptosis of chondrocytes can lead to fragility of the articular cartilage, resulting in fragmentation of the cartilage and formation of *loose bodies and *subchondral cysts in underlying bone
What is the female remnant of the inferior portion of the gubernaculum? What is its course?
The inferior portion becomes round ligament of the uterus (ligamentum teres uteri), which passes through the inguinal canal and attaches to the labia majora.
What is the female remnant of the superior portion of the gubernaculum? What does it connect
Proper ovarian ligament, which connects the uterus to the ovary
Episodic acute headaches, palpitations, flushing. Mass found in para-aortic region at level of aortic bifurcation.
Paraganglioma arising from chromaffin cells at the organ of Zuckerkandl. Similar to a pheochromocytoma, which would be in adrenal medulla.
In a Pulmonary Embolism patient, what is the mechanism for respiratory alklalosis?
Example pH 7.51, PaCO2 31, PaO2 66
CO2 is carried in blood as HCO3 and is not protein bound, CO2 removal is more directly dependent on ventialtion and there is large capacity for high V/Q regions to exhale additional CO2. Therefore, the result of hyperventilation is hypocapnia with respiratory alkalosis and persistent hypoxemia
BMPR2 mutation causes what pathology
-histology
Hereditary pulmonary arterial HTN—> progressive intimal fibrosis in concentric onion skin form w/ eventual development of plexiform lesions (capillary tufts)
What is the most common fibroid (leiomyoma) symptom?
Heavy menstrual bleeding
Which types of leiomyoma (fibroid) are most associated w/ anemia?
Submucosal/intracavitary
What is an endometrial polyp? Are they associated w/ uterine enlargement?
Benign overgrowth of the endometrial stroma. On histology they show numerous glands/vessels but not nuclear atypia or crowding. Do not cause uterine enlargement, but can cause intermenstrual bleeding
Crypt abscesses and multiple pseudopolyps
Ulcertaitve colitis
macrophages with accumulated PAS-positive granules
Whipple’s disease
Mucosal hemorrhage and patchy areas of necrosis in the bowels
Ischemic colitis
Patient presents at 2 years old with n/v, seizure, liver dysfunction, and hypoketotic hypoglycemia after prolonged fasting
MCAD deficiency: medium-chain acyl-CoA dehydrogenase deficiency, which is most common defect in beta-oxidation
How to remember the oncogenes
- ALK the Bs
- The Myc/kit
- The Rs
- The 2s
- ALK the Bs: ALK, bcr, bcl, braf
- The Myc/kit: myc, kit
- The Rs: kRas, Ret
- The 2s: Her2, Jak2
What enzyme will rifampin increase within hepatocytes? What effect does this have on warfarin metabolism in regards to kinetics? (Y-intercept, X-intercept changes in LB plot)
CYP29 is induced by rifampin, meaning concentration of that enzyme will increase in hepatocytes.
- this increases warfarin metabolism and corresponds to a rise in Vmax, which would lower the Y-intercept on a Lineweaver plott.
- enzyme induction increases the expression of an enzyme, but does NOT change its affinity for substrate. X-intercept remains the same
Nests or trabeculae of well-differentiated polygonal cells with eosinophilic cytoplasm and fine, granular chromatin. IH staining reveals presence of neuropeptides (chromogranin, synaptophysin)
Carcinoid tumor
-note that pheochromocytomas are also polygonal and stain for neuropeptides, but they are BASOphilic.
What method do apoptotic cells use that allows translation (usually in 5’ UTR) to begin in the middle of mRNA?
Internal Ribsome Entry
What are two important proteins that are upregulated by Thiazolidinediones (glitazone)?
- Glucose Transporter 4: insulin-responsive, transmembrane glucose transporter expressed in adipocytes and skeletal myocytes that increases uptake by target cells
- Adiponectin: cytokine secreted by fat tissue that lowers triglyceride levels by inducing differentiation of preadipocytes into insulin-responsive adipocytes and stimulating fatty acid oxidation
What is the MOA of lactulose in tx of hepatic encephalopathy?
Degraded by colonic bacteria to lactic acid and acetic acid; contents of the gi tract become *acidified, and NH3 is converted to NH4+**