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+**
What does the external branch of the superior laryngeal nerve (off the vagus) do? What artery runs w/ the external branch of superior laryngeal nerve?
Innervates the cricothyroid (only tensor muscle of larynx aiding with phonation, adduct/tighten cords)
Superior thyroid artery
The recurrent laryngeal nerves innervate all the intrinsic muscles of the larynx responsible for sound, except for the cricothyroid. What muscles does the recurrent nerve innervate?
Posterior/Lateral cricoarytenoids, oblique and transverse arytenoids, thyroarytenoid
What does the interal branch of the superior laryngeal nerve do?
Provides sensation over the SUPRAglottic area
All RNA viruses except for 2 replicate in the cytoplasm. What are the 2
Orthomyxo, retroviruses
What is implied by saying an RNA virus is negatively sensed
Must provide their own RNA-dependent RNA polymerase because a negative-sense RNA cant be used as a translation template.
What pathogen infects people in the San Joaquin valley, southern arizona, NM, Texas, South America, when they inhale arthroconidia from the soil?
Coccidioides immitis
Coccidiomycoses infection is normally asymptomatic or mild pneumonia w/ a pleural effusion. Rash and symmetric arthralgias can also occur.
-what is a more rare side effect that manifests in respiratory system?
thin-walled cavitity (singular) in the lung, patient may have hemoptysis in addition to fever and cough
Diffuse, intense lymphocytic infiltration of the thyroid gland by B and T cells specific for thyroid antigens.
-lymphoid germinal centers, Hurthle cells also present
Chronic autoimmune (Hashimoto) thyroiditis. Note that hurthle cells are metaplastic, enlarged epithelial cells w/ proment nucleoli and abundant eosinophilic cytoplasm.
Widely split and fixed S2
Atrial septal defect
In an X-linked recessive disorder with a non-carrier mother and an effected Father (XdY), what will the findings be in daughters vs sons
All daughters are carriers, they get Xd from dad and one healthy X from mom
All sons are normal. Get healthy X from mom, Y from dad
In an Xlinked recessive disorder in which the father is not a carrier, but the mother is a carrier (XXd) what are the findings in daughters and sons?
Daughters have 50% chance of becoming carriers
Sons have 50% chance of being AFFECTED
If sex is unknown, there would be 25% chance of having an affected child ([50% chance of having boy] X [50% chance of inheriting mutant dystrophin gene])
What are the histological findings of achalasia?
- inflammatory infiltrate of lymphocytes and eosinophils develops around NO producing neurons in the Myenteric (Auerbach) plexus.
- esophageal smooth muscle relaxation neurons are preferentially destroyed, whereas excitatory are spared
Where is broca’s area and what type of aphasia
Inferior frontal gyrus dominant (often left) hemisphere. Expressive (motor) aphasia
- characterized by slow speech consisting primarily of nouns and verbs, known as agrammatism
- preserved speech comprehension
How do you calculate Mean Arterial Pressure?
(SABP+2DABP)/3
Do postganglionic autonomic nervous system axons have myelin?
No. referred to as group C nerve fibers
What is standard error? What is its relationship to sample size?
SE is a measure of variability about the mean.
SE=standard deviation/sq. root of n(sample size)
Therefore, larger the sample size, the smaller the standard error of the mean
What are the viral characteristics of the Picornoviridae family
+sense, ssRNA virus
Naked, icosahedral, replicates in cytoplasm
What virus causes Lymphocytic Choriomeningitis Virus? What are its characteristics
Arenavirus
-sense, ssRNA, enveloped, ambisense, helical capsid, 2 segments
What region of HLA codes for MHC class II?
HLA-D
HLA-DP, HLA-DQ, HLA-DR
Which MHC has beta2 microglobulin?
MHC I
What is dermatitis herpetiformis associated with?
What is the histology?
Celiac; extremely pruitic lesions caused by cross-reactivity of anti-gliadin IgA antibodies w/ transglutaminase at the dermal basement membrane. Biopsy shows microabscesses at dermal papillary tips, which coalesce to form subepidermal blisters
What are the five layers of the EPIdermis from deep to superficial?
Basale, spinosum, granulosum, lucidum, corneum
What is the hyperinsulinemia and/or insulin resistance hypothesis of PCOS?
Hyperinsulinemia and/or insulin resistance is hypothesized to alter hypothalamic feedback, patients have increased LH:FSH ratio, which causes increased testosterone from theca interna cells. This decreases rate of follicular maturation, resulting in unruptured follicles (cysts) + anovulation.
Mature fibroblasts are injected with a retrovirus w/ genes encoding for human proteins. Modified fibroblasts then cultured and now are found to have pluripotent stem cells. What were the genes transferred from the retrovirus?
Transcription factors can induce cell differentiation, or de-differentiation as in this vignet
What would you use to constrict a pupil in a denervated eye:
Physostigmine, or Pilocarpine? Why?
You would use pilocarpine because it is a direct cholinergic muscarinig AGONIST.
Phystigmine is an indirect cholinergic agonist that works by inhibition of anticholinesterase by increasing ACh. (Note it is a tertiary amine so it can cross the BBB)
Fatigue, peripheral neurpathy, atrophic glossitis. Blood smear shows macrocytosis and hypersegmented neutrophil.
Pernicious anemia due to autoimmune destruction of gastric mucosa
Why would you see increased gastrin levels in someone with pernicious anemia?
Autoimmune destruction of gastric mucosa leads to atrophic gastritis, causing profound HYPOchlorhydria, leading to a compensatory increase in serum gastrin levels (antral G cell gastrin section is normally inhibited by HCL)
How does leuprolide work?
GnRH agonist; when used continuously suppresses pituitary LH release, and leads to reduced production of testosterone by Leydig cells.
CATCH-22 mnemonic for DiGeorge
22q11.2 deletion Conotruncal cardiac defects Abnormal facies Thymic aplasia/hypoplasia Cleft palate Hypocalcemia (absent parathyroid)
-3rd, 4th pharyngeal pouches
What is a diagnostic finding for hyper-IgM syndrome?
Inheritance pattern of hyper-IgM
Absence of CD40L (cd40 ligand) on T cells.
X-linked recessive
What drug would you give for CML and why?
Imatinib; inhibits Bcr-Abl tyrosine kinase product.
Is the COX-2 enzyme found within platelets?
No, only COX-1
What is the action of aspirin on platelets?
Irreversibly inhibit COX-1 in platelets, which prevents synthesis of TXA2, a potent stimulator of platelet aggregation and vasoconstriction.
What is the adult remnant of the umbilical arteries?
Medial umbilical ligament
What is the adult remnant of the umbilical vein?
Ligamentum teres
What is the adult remnant of the Ductus venosus?
Ligamentum venosum
What does the ductus venosus do?
Blood flows from placenta into fetus via umbilical vein. Then flows to fetal liver, where it may be diverted into the IVC via the ductus venosus
What can sometimes be used for central vascular access and resuscitation of a critically ill neonate?
Umbilical vessels. Complete closure of ductus venosus does not occur until about 1 week after birth, although the structure is functionally closed within hours of birth. The catheter would pass through the umbilical vein and ductus venosus until the tip reaches the IVC at the junction of the right atrium
Describe the azygos vein system
On left upper thorax, accessory hemiazygos vein, inferiorly you have hemiazygos vein. Both of those cross over to the right side of the vertebral column where they drain into the azygos vein proper, which dumps into the SVC
What changes occur after birth that force the thin septum primum against the thick septum secundum, closing off the foramen ovale?
Increase in left atrial pressure, decrease in right heart pressure, and decrease in pulmonary vascular resistance. (high LA pressure pushes against left-lateral side of septum primum, pushing it against septum secundum)
What fungus has asexual fruiting structures known as conidiophores when stained with methenamine silver?
Aspergillus
What mechanism of bacterial gene transfer is characterized as: Direct uptake of naked DNA from the environment?
Transformation
Which method of bacterial gene transfer is a one-way transfer of chromosomal or plasmid DNA?
Conjugation
Donor cell F factor DNA codes for sex pilus, bacteria that lack F factor serve as recipient cells.
What is generalized transduction of DNA by a bacteriophage?
Packaging of random bacterial genes into virion during lytic infection
What is specialized transfuction of DNA by bacteriophage?
Packaging of specific bacterial genes near the viral insertion site during lysogenic infection
What four bacteria are well known to take up foreign DNA and incorporate it into their own genome (referred to as competent)?
This is transformation Haemophilus Streptococcus Bacillus Neisseria
Why does DNase inhibit the process of transformation?
When bacteria are lysed, the DNA is exposed in the culture medium where DNase can get to it
Which nephrotic syndrome is associated with HIV infection, heroin addiction, and sickle cell disease?
Focal Segmental Glomerulosclerosis FSGS
What is a defining characteristic of the FSGS seen in HIV patients?
Collapsing glomerulopathy, which is a poor prognostic indicator
If pleural pressure exceeds atmospheric pressure
Tension pneumothorax
HOXA13 mutation causes which syndrome? Findings?
Hand-foot-genital syndrome
-malformation of the distal limbs such as hypoplastic first digits, and Mullerian fusion abnormalities (uterus didelphys).
PAX6 mutations
Ocular defects such as absent iris (aniridia)
In regards to skeletal muscle, decreasing which force would increase contraction velocity?
Decreasing afterload; the force against which the muscle fiber must contract.
The triad of sudden-onset flank pain, gross hematuria, and oliguria in a patient w/ a high anion gap metabolic acidosis suggests poisioning with what?
Ethylene glycol
What are the toxic metabolites that cause pathology in a patient who has OD’ed on ethylene glycol?
- glycolate is cytotoxic to renal tubules and causes acute tubular necrosis
- glycolate is further metabolized to oxalate, which contributes to oliguric renal failure by precipitating in the kidneys and causing tubular obstruction.
What type of crystals would you see in urine microscopy of someone who has overdosed with ethylene glycol?
Dumbell-shaped or envelope shaped calcium oxalate crystals
What and where is the drainage of the maxillary sinus?
Semilunar hiatus in the middle nasal meatus. Located superior to the floor of the sinus, so drainage is impaired while upright.
What is the region of the sarcomere containing the Z line and only those sections of the thin (actin) filaments that do not overlap with thick (myosin) filaments?
I band
What happends to the width of the I band during muscle relaxation and contraction?
I band lenghthens during muscle relaxation, shortens during contraction
