Week of March 9th Flashcards
What is the urachus?
Remnant of the ALLANTOIS that connects the bladder with the yolk sac during fetal development. Should obliterate by birth.
Failure of urachus to obliterate before birth results in what abnormalities?
- Patent Urachus: connects umbilicus and bladder. Urine discharge from umbilicus exacerbated by crying, straining, voiding and prone position.
- Vesicourachal Diverticulum: fail to close proximal part of urachus adjacent to bladder. Asymptomatic outpouching of bladder apex.
- Urachal Sinus: fail to close distal part of urachus adjacent to umbilicus. Periumbilical tenderness and purulent discharge from umbilicus d/t persistent/recurrent infections.
- Urachal Cyst: fail to obliterate central portion of urachus; asymptomatic fluid filled structure.
**652
Describe 21-hydroxylase deficiency
Most common cause of congential adrenal hyperplasia. Salt-wasting. Deficient cortisol (increased ACTH)** and aldosterone synthesis** combined with adrenal androgen overproduction. Also increased 17-hydroxyprogesterone as its conversion to 11-deoxycortisol is impaired.
- Male: normal genitalial and present 1-2w after birth with **vomit, hypotension, hyponatremia, hyperkalemia **
- Female: at birth with ambiguous genitalia (virilization)
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Describe the course of the IVC
Courses through abdomen anterior to right half of the vertebral bodies. Renal veins join IVC at L1/L2, and common iliac veins merge to become the IVC at L4.
An IVC filter can prevent travel of DVTs from legs to lung vasculature and is used to prevent pulmonary embolism in patients with CI to anticoagulation.
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Why is acyclovir and related drugs more effective agaisnt HSV and VSV than CMV and EBV?
EBV and CMV do not produce the same thymidine kinase that HSV/VSV do and thus cannot easily convert acyclovir into its pharmacologiclaly active triphosphate form.
- Monophosphorylation of acyclovir by viral TK is the first (and rate-limiting) step in the conversion of acyclovir to its active triphosphate form, which impairs viral DNA polymerase-mediated replication of virus.
- 1645*
Describe the acid-base physiology of high altitude
- Reduction in barometric pressure causes concomitant reduction in inspired partial pressure of oxygen, which causes **decreased PaO2 **
- Resulting hypoxemia stimulates carotid/aortic body chemoreceptors to increase ventilation
- Hyperventilation and respiratory alkalosis cause increase blood pH and **reduced PaCO2. **
- To partially compensate for respiratory alkalosis, kidneys begin to excrete HCO3- in the urine, thereby causing a mild metabolic acidosis through decreased serum bicarb. Renal compensation begins within 48 hours after onset of hyperventilation.
- Within a few hours of being at high elevation, hypoxia begins to stimulate renal production of erythropoietin which results in increased RBC production wtih concomitant increase in hemoglobin levels begining at 10-14 days.
- Additional compensatory changes - increase in capillary density, [myoglobin], and cellular mitochodnria counts
1980
Describe cricothyrotomy incision
Skin –> superficial cervical fascia (including subcutaneous fat and platysma muscle) –> investing and pretracheal layers of deep cervical fascia –> cricothyroid membrane.
Direct inguinal hernias are associated with what?
Protrude through Hesselbach’s triangle, which is formed by the inguinal ligament inferiorly, the inferior epigastric vessels laterally, and the rectus abdominus muscle medially. The transversalis fascia forms the floor, and defects/weakness can lead to protrusion of abdominal contents through triangle into inguinal canal.
- Do not pass through deep inguinal ring but pass only through superficial inguinal ring.
- Covered only by external spermatic fascia.
- MC in elderly men.
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Describe hyperacute, acute, and chronic rejection of lung transplant
- Hyperacute - within minutes; preformed antibodies against ABO or HLA
- Acute - 1-2 weeks post-transplant; rxn to HLA of graft; CD8 T cell response causing vascular damage with preivascular and peribronchial lymphocytic infiltrates.
- Chronic - months-years post-transplant. Inflammation of small bronchioles/aka small airways (i.e. bronchiolitis obliterans).
What meds should be avoided with benzodiazepines (e.g. diazepam)
SE - sedation (MC), impaired coordination/balance, decrease memory/concentration, confusion. These effects are amplified by co-administration of other CNS depressants. CI with alcohol, barbs, neuroleptics, or 1st generation antihistamines (e.g. chlorpheniramine, diphenhydramine, promethazine, and hyroxyzine)
Whats the difference between heterochromatin adn euchromatin?
- Herterochromatin: condensed and methylated DNA that has low level of transcriptional activity. Once X-chromsome in female is normally randomly deactivated by this process to form Barr body.
- Euchromtin: loosely aranged chromatin formed by histone acetyltation that has high transcriptional activity
When might you see migratory superficial thrombophlebitis?
AKA “Trousseau’s syndrome” (superficial venous thromboses appearing in one site and then recurring in another) is an indication of visceral cancer. A paraneoplastic syndrome of hypercoaguability may be seen in some patients wtih cancer, especially adenocarcinomas of pancreas, colon, or lung.
What is niacin (vitamin B3) endogenously synthesized from?
Tryptophan. Deficiency of niacin results in pellagra, characterized by the 3 D’s: dermatitis (rough, thick, scaly skin on sun-exposed areas), diarrhea (d/t columinar atrophy), dementia.
What is Cheyne-Stokes respiration and when is it seen?
Describes cyclic breathing in which apnea is followed by gradually increased tidal volumes, and then gradually decreasing tidal volumes until the next apneic period. D/t slow respiratory feedback loop with enhanced respiratory response to PaCO2 levels - slowed feedback delays the respiratory response allowing PaCO2 to rise higher than it normally would.
Commonly seen in cardiac disease (advanced CHF) and neurologic disease (stroke, brain tumors, traumatic brain injury).
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Describe the fantasy defense mechanism
Immature defense mechanism that substitutes an imaginary, less distrubing view of the world to avoid awareness of painful feelings (e.g. mother’s fantasy of her son playing major league baseball adn livign a long life offering an escape from anxiety about his illness).
The gene translocated in lymphoid cells of Burkitt lymphoma performs which function?
Characterized by aggressive, rapid growth and a “starry-sky” microscopic apperance.
Demonstrate a translocation of the c-myc oncogene on long arm of ch. 8 with Ig heavy chain region on ch. 14 [t(8;14)]. The product of c-myc is a nuclear phosphoprotein that functions as a transcription activator controlling cell proliferation, differentiation, and apoptosis.
A pregnant women states she is eating a lot of ice. What should you assess this patient for?
Pica - compulsive consumption of nonfood and/or non-staple food. It is common in pregnancy. Ice is the most common ingested substance. Pregnant patients shoudl be assesed throughout pregnancy, especially if there is unexplained weight loss. It is often seen in association wtih iron deficiency anemia.
What is not transcribed from the DNA template?
The polyadenylation signal sequence at the 3’ end of the mRNA transcript is responsible for the addition of the poly-A tail, which is not transcribed from DNA but rather added as a posttranscriptional modification downstream of a consensensus sequence (usually “AAUAAA”). This tail protects mRNA from degradation within the cytoplasm after it exits the nucleus.
- Remember RNA pol II forms pre-mRNA from DNA template which undergoes posttranscriptional processing (i.e. 5’ cap, polyadenylation, and splicing) to form mature mRNA, which exports nucleus and is translated.
Glutamate residues of some proteins synthesized in pre-mature infants liver fail to be carboxylated. What nutrient deficiency is responsible?
Vitamin K is essential cofactor for hepatic microscomal carboxylase that converts glutamyl residues into y-carboxyglutamates, which is critical for functionality of clotting factors 7, 9, 10, protein C and S. Deficiency can be found in 1) malabsorption syndromes, 2) long-term broad-spectrum ABX that destroy intestinal flora, as endogenous colonic bacterial flora generate vitamin 3) neonates and 4) those with liver disease.
What is the drug of choice for myoclonic seizures and what is the MOA
Valproic acid - supresses abnormal electric activity in the cortex by affecting GABA and NMDA receptors, as well as Na+ and K+ channels.
Myoclonic syndromes characterized by repeptivie seizures of brief, often symmetric, muscular contractiosn with loss of body tone cuasing patient to fall or slump forward. Usually occur in morning and are precipitated by stress and sleep deprivation.
What is the cause and treatment of Conn’s syndrome
Aldosterone secreting tumor (adenoma) leading to hyperaldosteronism with Sx of HTN, hypokalemia, metabolic alkalosis, and decreased renin. Tx with aldosterone antagonists including spironolactone or eplerenone.
What has the Haemophilus influenzae type b conjugate vaccine reduced incidence of?
Capsular type b is the most invasive strain of H. influenzae and can cause sepsis, meningitis, and pneumonia.
- This vaccine has no effect on nontypable strains, as the Hib vaccine induces immunity specificially agaisnt the type b polysaccharide capsule, and nontypable strains do not produce capsules.
- Composed of polyribosyl-ribitol-phosphate (PRP), a component of the Hib capsule, conjugated with diphtheria or tetanus toxoid.
- Epiglottitis is almost exclusively caused by type b.
How do beta blockers work and what is the downside of nonspecific blockade
BBs reduce BP and cardiac work, which is benefical in acute MI treatment. Work by inhibiting the NT-receptor interaction in adrenergic synapses. B1 receptor blockade decreases HR while B2 adrenegic blockade casues bronchoconstriction and wheezing. An adverse effect of BBs that cause **nonspecific blockade is increased difficulty breathing in patients with asthma/COPD. **
Describe the murmur of aortic stenosis
Systolic ejection-type crescendo-decrescendo murmur that starts after the first heart sound and ends before A2 component of second heart sound. The intensity of the murmur is proportional to the magnitude of the LV to aorta pressure gradient during systole.
Asplenic sickle cell patients are at risk of what
Risk for infection with encapsulated organisms (most common is Strep pneumoniae > H. influenzae). Can develop septicemia (fever, chills, elevated WBC, neutrophilia) due to endotoxins found in gram-negative bacerial cell wall.
What is the Hawthorne effect?
Observer effect; tendency of study subjects to change their behavior as a result of their awareness that they are being studied
Mental retardation, eczema, and a “mousy” or musty body odor in a toddler are signs of what?
PKU, an AR disease caused by mutation of gene that codes for phenylalanine hydroxylase. Most infants with PKU are born to two heterozygous carrier parents (1/4 risk for disease).
Describe the metyrapone stimulation test
Indicator of HPA axis integrity. Metyrapone blocks cortisol synthesis by inhibitng 11-B-hydroxylase which converts 11-deoxycortisol to cortisol in the zona fasciculata. The reduction in cortisol causes an increase in pituitary ACTH, leading to increased prodcution of 11-deoxycortisol, which is further metabolized by liver to 17-hydroxycorticosteroids that accumulate in urine. Failure of these steroid levels to increase implies primary or secondary adrenal insufficeincy, which can be distinguished based on plasma ACTH.
What are the important risk factors and S/Sx for pancreatic cancer?
**Smoking **is the most important environmental risk factor. Age > 50 y/o, chronic pancreatitis, diabetes mellitus, and genetic predisposition (hereditary pancreatits, MEN, hereditary nonpolyposis colon cancer, and FAP) also increase the risk of this malignancy.
Palpable but nontender gallbladder (Courvoisier sign), weight loss, and obstructive jaundice (associated with pruritis, dark urine, and pale stools) are indicative of adenocarcinoma at head of pancreas compressing common bile duct.
What does the arteriovenous concentration gradient of an anesthetic reflect?
Reflects the overall tissue solubility of an anesthetic. Anesthetics with high tissue solubility are characterized by a large arteriovenous concentration gradients and slower onsets of action.
- Before gas anesthetic can reach the target organ (brain), they must move through a number of compartments (inhaled air –> lungs –> blood –> brain). The onset of anesthesia occurs when sufficient quantity of anesthetic is transferred to brain.
- AV concentration gradient is difference between concentration of gas anesthetic in arterial and venous blood. The solubility of anesthetic in peripheral tissues is a major factor in determining the size of AV gradient. If tissue solubility is high, a large amount of anesthetic is taken up from arterial blood, which results in a low venous concentration. Thus, saturation of blood requires further absorption of anestheic in order to replace that which is absorbed by peripheral tissues. Becuase blood saturation takes longer, brain saturation is also delayed and onset of action is slower.
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Describe the factors that influence the rate of transfer of anestheic through the compartments and determine the onset of action.
- Inhaled Air: partial pressure (tension) of anesthetic in inspired gas. Anesthetic tension throughout body will eventually equilibrate with its tension in inspired air. When this occurs, the tissues are saturated.
- Lungs: pulmonary ventilation rate. The rate of rise of gas tension in alveoli is directly proportional to both the rate and depth of respiration.
- Blood: solubility of anesthetic in blood (blood/gas partition coefficient). Higher blood solubility means that more anesthetic must be absorbed by blood before it can be effectively transferred to other tissues.
- Target Organ (Brain): solubility of anesthetic in peripehral tissues negatively affects brain saturation. Higher peripheral solubility means more anesthetic is extracted from arterial blood. This increases AV concentration gradient, meaning more anesthetic must be absorbed to saturate blood and then the brain.
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What are the stop codons and what are mutations producing abnormally placed stop codons called?
Stop codons include: UGA, UAG, UAA
Nonsense Mutations: introduction of a stop codon in the middle of a portein sequence. Result in premature termination of protein synthesis and formation of a truncated protein molecule.
How does Neisseria meningitidis gain access to the CNS?
Bean-shaped Gram negative cocci in pairs (higher risk: new military recruits, college freshmen) first colonizes the nasopharynx and subsequently invades the mucosal epithelium to gain access to bloodstream. Through the blood, it spread to choroid plexus, gains access to CNS through BBB, and initates an inflammatory process.
- In meningococcemia, there may be S/Sx of sepsis and characteristic petechial skin lesions.
- In fulminant meningococcemia (Waterhouse-Friderichsen syndrome), bilateral adrenal hemorrhage causes adrenal insufficeincy, brisk hypotension, and death.
Which organism embodies each of the following mechanisms of spread?
- Pharynx –> lymphatics –> meninges
- Middle ear –> contiguous tissues –> meninges
- Traumatic wound –> leaking CSF –> meninges
- Primary lung focus –> blood –> meninges
- Pharynx –> lymphatics –> meninges = H. influenzae; infants and children
- Middle ear –> contiguous tissues –> meninges = S. pneumoniae during acute infection of middle ear
- Traumatic wound –> leaking CSF –> meninges = S. aureus
- Primary lung focus –> blood –> meninges = M. tuberculosis (chronic meningiits, characterized by monocytes and lymphocytes in CSF, primarily affecting basal meninges) or S. pneumoniae.
On a pedigree, if each of the affected individuals has inherited the disorder from asymptomatic parents, what is the inheritance pattern? Also what diseases generally follow this inheritance pattern?
Autosomal Recessive conditions affect 25% of offspring of asymptomatic heterozygous carrier parents. Classic galactosemia is an AR disease where patients are homozygous for a defective galactose-1-phopshate uridyltransferase gene. In general, most enzyme deficiency conditions follow an AR inheritance pattern, whereas diseases due to defective non-catalytic proteins tend to follow AD pattern where affected indiviudals generally have one affected parent.
How do enzyme deficiencies of the early steps in porphyrin synthesis differ from later steps?
Porphyrias: hereditary or acquired conditions of defective heme synthesis that lead to accumulation of heme precursors.
- Enzyme deficiencies of the early steps in porphyrin synthesis cause neuropsychiatric manifestations without photosensitivity, while late step derangements (after the condensation of porphobilinogen) lead to photosensitivity (porphyria cutanea tarda most commonly).
- More specifically, defects in URO decarboxylase, COPRO oxidase, PROTO oxidase, and Ferrochetalase result in photosensitivty.
- Photosensitivty is thought to be mediated by formation of porphyrin-mediated superoxide free radicals from oxgen upon exposure to sunlight. It cause vesicle and blister formation on sun-exposed areas as well as edema, pruritus, pain, and erythema.
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What is a type I error, type II error, alpha, beta, and 1 - beta?
- Type I Error: reject null when null is really true. alpha is the maximum probabiliy of making a type I error that a research is willing to accept. Generally alpha is compared to the p-value, the probability of observing a given result (or more extreme) due to chance alone assuming null is true (eg, if no real difference between groups). The value of alpha is typically set at 0.05, meaning that reserachers are willing to accept up to a 5% chance of making a type 1 error. Thus if **p <0.05, the result is said to be statistically signficiant. **
- Type II Error: fail to reject null when it is truely false (e.g. aspirin does not affect platelet fxn when in fact it does). Beta is the probability of comitting a type II error.
- Stastical power (1 - beta): represents a study’s ability to detect a difference when one exists. It is the probability of rejecitng the null when it is truly false - i.e. the probability of findign a true relationship. Depends on sample size and difference in outcome betwen the groups being tested.
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In situtations in which a parent’s presence may interfere with obtaining honest answers from an adolescent patietn, whould you do?
Politely ask the parent to wait outside and interview the patient privately. This is also important when discussing drugs, EtOH, tobacco, and sexual activity with teens.
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During physical exam, you palpate several hard lymph nodes in the right inguinal area. What lymph nodes are these and what do they drain?
Superficial inguinal lymph nodes drain all of the cutaneous lymph from the umbilicus to the feet, including the external genitalia and anus (up to the beginnning of the rectum, the dentate line), but excluding the posterior calf, which drains to the popliteal lymph nodes.
- Lie in a region bounded by the inguinal ligament, sartorius muscle, and adductor longus m uscle, and overlie the femoral nerve, artery, and vein.
- 1631*
Describe the presentation and treatment of age-related macular degeneration (AMD)
- Degeneration of central retina and presents as difficulty with driving and reading.
- Classified as DRY (subretinal drusen deposists or pigment changes; presents as gradual vision loss in one or both eyes and usually progresses to wet AMD) or WET (abnormal blod vessels with subretinal fluid/hemorrhage, gray subretinal membrane, or neovascularization; more common, with acute vision loss over a period of days to weeks) VEGF is the major cause of wet AMD and causes retinal neovascularization.
- Dry and less-advanced wet AMD may be treated with antioxidant vitamins and zinc.
- Active and more-advanced wet AMD require specific treatment with anti-vascular endothelial growth factor (VEGF) inhibitors, which limit the development of choroidal neovascular membranes; include intravitreous ranibizumab (preferred recombinant humanized monoclonal antibody) and pegaptanib. Can also use laser therapy or phototherapy.
Describe the MAO and SE of Niacin, Statins, and Bile Acid Resins
- Nicotinic Acid (Niacin, vitamin B3): inhibit hepatic VLDL production and is used to increase HDL levels. SE include flushing (prevented with pre-treatment with aspirin), hepatotoxicity with high doses, and worsening hyperglycemia in diabetics.
- Statins: inhibit cholesterol synthesis (inhibit HmG-CoA reductase) and thereby **up-regulte LDL receptors **
- Bile Acid Resins (e.g. cholestyramine and colestipol): bind to bile acids in GI tract and interfere with its enterohepatic circulation. LDL is reduced as a result. SE include constipation and abdominal bloating (potentially worsening diverticulosis), hypertriglyceridemia, cholesterol gallstones, and vitamin K malabsorption.
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When do you hear the fourth heart sound and what is it associated with?
Heard at end of diastole just before S1. It is due to decreased LV compliance and is often associated with resitrictive cardiomyopathy and left ventricular hypertrophy.
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How does ectopic pregnancy present and what is the main risk factor?
Occurs when a fertilized ovum implants outside of the uterus (ampulla of fallopian tube). The main risk factor is a hx of PID. With time, ectopic pregnancy compromises the blood supply to surrounding tissues and can lead to organ rupture. A patient with ruptured ectopic pregnancy might present with abdominal pain, vaginal bleeding, and signs of hemorrhagic shock (low BP, tachycardia, cold clammy extremities, and oliguria). Although there is no embryo present inside the uterine cavity, the hormonal changes that occur are identical to those that occur during a normal pregnancy. Thus a uterine biopsy or curretage would reveal pregnancy-related endometrial changes (such as decidualization of stroma) without embryonci tissue or chorionic villi.
What does reduction in the slope of a curve depicting lung volume versus distending pressure indicate?
Decreased lung compliance (the hallmark of pulmonary fibrosis) where for any given volume, the pressure will be significantly increased. NOTE: in emphysema, the lung parenchyma has increased compliance.
Describe Leprosy or Hansen Disease
Deforming infection primarily of the skin and nerves and is caused by Mycobacterium leprae. The most severe form is “lepromatous leprosy” and occurs in patients with a weak cell-mediated (TH1) immune response such that macrophages are never given the signal to kill the mycobacterial organisms, allowing M. leprae to multiply/disseminate (invade Schwann cells). Clinically manifests as **diffuse skin thickening, cutaneous hypopigmentation in plaques (often accompanied by hair loss), leonine facies, paresis and regional anesthesia of motor and sensory nerves, and testisticular destruction and blindness. **
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Describe the pathway in the generation of ammonia
Ammonia is generated from the metabolism of alpha AAs and is normally converted to urea by the urea cycle which involves 5 steps: 2 in the mitochondrial matrix and 3 in teh cytosol. One more enzyme that indirectly participates in is N-acetylglutamate synthetase (NAGS).
- First step: CO2, ammonia, and ATP are combined to form carbamoyl phopshate via carbamoyl phopshate synthetase I (rate-limiting step).
- N-acetylglutamate (NAG) is an essential activator of CPS and is formed by the enzyme NAGS from the precursors acetyl-CoA and glutamate.
Formation of N-acetylglutamate impaired: first few feedings provide a protein load to infant that results in AA being available for metabolism, but defect in urea cycle prevents disposal of toxic ammonia from childs body –> **lethargy, vomitting, and seizures **
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Where does the majority of water reabsorption in nephron occur?
Regardless of hydration status, majority occurs in the proximal tubule (>60% of water filtered by glomeruli) passively with the reabsorption of solutes.
In dehydrated state, plasma osmolarity increases, stimulating osmoreceptors in anterior hypothalamus –> increased ADH promotes aquaproin (water channel) insertion into apical membranes of principal cells lining the late distal tubules and collecting ducts. Allows for production of maximally concentrated urine (osmolarity of 1200 mOsm/L). Up to 20% of the original filtered voluem of water can be reabsorbed here, allowing >99% of filtered water to be reabsorbed by the neprhon during dehdyration.
Describe the MOA of the 4 commonly used clinical disinfectants
- Alcohols (isopropanol, ethanol): disrupts lipid structure in membranes (causing them to be leaky), denaturation of proteins. They are bactericidal, tuberculocidal, fungicidal, and virucidal, but do not destroy bacterial spores.
- Chlorhexidine: disruption of cell membranes, coagulation of cytoplasm
- Hydrogen peroxide: produces destructive free radicals that oxidize cellular components (SPORICIDAL)
- Iodine: halogenation of proteins and nucleic acids (SPORICIDAL)
Describe one of the main neurological SE of Isoniazid treatment
Structurally similar to pyridoxine (vitamin B6). This ABX increases the urinary excretion of pyridoxine (often cuasing a frank deficiency of vitmain B6) and competes for vitamin B6-binding sites, leading to the defective synthesis of NTs like GABA. Isoniazid-induced neuropathy can usually be prevented with pyridoxine supplementation.
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Why does focal dimpling of the skin and inversion of the nipple occur with invasive breast cancer?
Nipple inversion is observed when the tumor invades the central region of the breast, and skin retraction is identified when the cancer infiltrates the suspensory Cooper ligaments. Should the lymphatic drainage become impeded by the tumor there will be** lymphadema, pitting, and thickening of the skin** such that the skin adopts the apperance of an orange peel (peau d’orange) which is particuarly common in patients with inflammatory breast cancer.
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What is the genetic cause for Turner’s Syndrome?
May have the karyotype 45,XO (complete monosomy), 45XO/46XX (mosaicism), or 46XX (“partial monosomy,” with partial deletion of one X chromosome). Monosomy appears to acount for the majority of cases.
- In the mosaic population, one genetic line contains cells with a normal number of chromosomes (46,XX), while the other genetic line contains cells that are monosomic (45,XO); both lines originate from a single zygote.
- In most cases of monosomy X, the etiology is loss of the parental X chromosome during mitosis; in the cases of other forms of aneuploidy, the tiology is meitoic nondisjunction. Mosaicism arises secondary to mitotic errors after fertilization has taken place.
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