Week of March 9th Flashcards
1
Q
What is the urachus?
A
Remnant of the ALLANTOIS that connects the bladder with the yolk sac during fetal development. Should obliterate by birth.
2
Q
Failure of urachus to obliterate before birth results in what abnormalities?
A
- 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
3
Q
Describe 21-hydroxylase deficiency
A
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)
*930 *
4
Q
Describe the course of the IVC
A
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.
1538
5
Q
Why is acyclovir and related drugs more effective agaisnt HSV and VSV than CMV and EBV?
A
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*
6
Q
Describe the acid-base physiology of high altitude
A
- 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
7
Q
Describe cricothyrotomy incision
A
Skin –> superficial cervical fascia (including subcutaneous fat and platysma muscle) –> investing and pretracheal layers of deep cervical fascia –> cricothyroid membrane.
8
Q
Direct inguinal hernias are associated with what?
A
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.
8669
9
Q
Describe hyperacute, acute, and chronic rejection of lung transplant
A
- 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).
10
Q
What meds should be avoided with benzodiazepines (e.g. diazepam)
A
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)
11
Q
Whats the difference between heterochromatin adn euchromatin?
A
- 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
12
Q
When might you see migratory superficial thrombophlebitis?
A
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.
13
Q
What is niacin (vitamin B3) endogenously synthesized from?
A
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.
14
Q
What is Cheyne-Stokes respiration and when is it seen?
A
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).
8262
15
Q
Describe the fantasy defense mechanism
A
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).
16
Q
The gene translocated in lymphoid cells of Burkitt lymphoma performs which function?
A
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.
17
Q
A pregnant women states she is eating a lot of ice. What should you assess this patient for?
A
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.
18
Q
What is not transcribed from the DNA template?
A
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.
19
Q
Glutamate residues of some proteins synthesized in pre-mature infants liver fail to be carboxylated. What nutrient deficiency is responsible?
A
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.
20
Q
What is the drug of choice for myoclonic seizures and what is the MOA
A
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.
21
Q
What is the cause and treatment of Conn’s syndrome
A
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.
22
Q
What has the Haemophilus influenzae type b conjugate vaccine reduced incidence of?
A
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.
23
Q
How do beta blockers work and what is the downside of nonspecific blockade
A
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. **
24
Q
Describe the murmur of aortic stenosis
A
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.
25
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.
26
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
27
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).
28
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.
29
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.
30
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.
*660*
31
Describe the factors that influence the rate of transfer of anestheic through the compartments and determine the onset of action.
1. _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**.
2. _Lungs_: *pulmonary ventilation rate*. The **rate of rise of gas tension in alveoli is directly proportional to both the rate and depth of respiration**.
3. _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.
4. _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**.
## Footnote
*660*
32
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.
33
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.**
34
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**.
35
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.
36
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**.
*1337*
37
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.
## Footnote
*1272*
38
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.
## Footnote
*1126*
39
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*
40
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.
41
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**.
## Footnote
*785*
42
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.
## Footnote
*2107 with media*
43
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**.
44
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.
45
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. **
## Footnote
*1313*
46
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 **
*1371*
47
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.
48
Describe the MOA of the 4 commonly used clinical disinfectants
1. _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.
2. _Chlorhexidine_: disruption of cell membranes, coagulation of cytoplasm
3. _Hydrogen peroxide_: produces destructive free radicals that oxidize cellular components (SPORICIDAL)
4. _Iodine_: halogenation of proteins and nucleic acids (SPORICIDAL)
49
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**.
## Footnote
*1308*
50
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_.
## Footnote
*1056*
51
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.
*1810*
52
Describe Bruton's agammaglobulinemia
* **X-linked immunodeficiency** resulting in **abscence of B cells and all forms of immunoglobulin** due to a defect in a B cell maturation. Due to abscence of B cells, **germinal centers and primary lymphoid follicles will not form within cortex of lymph nodes**.
* Germinal centers contained within lymphoid follicles are where B lymphocytes normally go to proliferate and undergo somatic hypermutation after exposure to antigen.
* Predisposed to **recurrent pneumonias which begin when child is \<1 y/o.**
* **T cell numbers and function are intact** (indicated by positive reaction to Candida antigen; i.e. development of indurated nodule within 48h of intradermal Candida extract injection).
* Remember that T lymphocytes and dendritic cells are housed in the paracortical zone.
## Footnote
*1134*
53
What is a Mallory-Weiss tear and what acid-base abnormality is it associated with?
Tear in gastric mucosa near the gastroesophageal junction that is typically the result of repetitive, forecful vomitting, which can lead to **metabolic alkalosis** due to net loss of acidic gastric secretions.
54
What is the preferred treatment for patients with a combination of both tonic-clonic and abscence seizures?
**Valproate** is the drug of choice, becuase while Ethosuximide is effective against abscence seizures it does not supress tonic-clonic seizures.
55
What is the most common cause of acute pancreatitis?
**Alcohol abuse** is one of the two most common causes (gallstones are the other). **Macrocytosis**, an **AST:ALT ratio \>2,** and **elevated GGT** are indirect indicators of chronic alcohol consumption. Macrocytosis may occur secondary to poor nutrition (folate or vitamin B12/cobalamin deficiency), but may also result from direct toxicity of alcohol on the marrow.
56
In a susceptible child, a febrile maculopapulr rash that begins on face and spareads to trunks and extremities is suggestive of what?
**Rubeola** (measles; *Paramyxovirus*) or **Rubella** (German measles; caused by *Togavirus*). The additional finding of **postauricular and occipital LAD** indicates that rubella is a more likely etiology. Also compared to rubeola, the rash of rubella typically spreads faster and does not darken or coalesce.
57
During an attempt to retrieve food that become lodged in the left piriform recess, a nerve was injured. What is the nerve and what would be S/Sx?
**Internal laryngeal nerve** (branch of the superior laryngeal nerve of CN X) mediates afferent limb of cough reflex above the vocal folds. Foreign bodies (eg chicken or fish bones) can become lodged here and can cause damage to the nerve, impairing the cough reflex.
58
Which cells demonstrate a high activity of an enzyme that has reverse transcriptase activity, which adds TTAGGG repeats to the 3' end of chromsomes?
**Telomerase** is a reverse transcriptase enzyme (RNA-dependent DNA polymerase) that adds TTAGGG repeats to the 3' end of DNA strands at the terminal end of chromsomes, the telomere region. It is simmilar to other reverse transcriptase enzymes in that it synthesizes single-stranded DNA using single-stranded RNA as template. It is noramlly expressed in **stem cells** as well as **cancer cells**. However, cancer cells are immortal becuase these cells continue to divide wtihout aging and shortening of their telomeres.
59
Describe the process of T cell maturation
* Pro-T cells arrive at the thymus as "double negative" cells indicating that they lack both CD4/8 and begin their diferentation in the **subcapsular zone. **
* _Positive selection_ - only T cells expressing a TCR that is able to bind self MHC are allowed to survive, and occurs after TCR DNA rearrangement. Occurs in thymic cortex and involves interaction of T cells with **thymic cortical epithelial cells expressing self MHC. **
* _Negative selection_ - after positive selection, T cells possessing TCR that bind with high affinity to self antigen or self MHC are eliminated by apoptosis. Occurs in thymic medulla and involves interaction fo the devloping T cells with **thymic medullary epithelial and dendritic cells**.
60
A 75 y/o F brought to your office because of worsening forgetfulness over past few years. Disorietnated to time and can only recall 1/3 items on short term memory test. MRI shows diffuse cortical atrophy. Whats your treatment?
Chronically progressive dementia + cortical atrophy --\> **Alzheimer's Disease**.
* Enhanced cholinergic neurotransmission with **donepezil (cholinesterase inhibitor)** which improves cognition, bheavior, and functioning.
* Neuroprotection via antioxidants including **vitamin E (alpha-tocopherol)**
* NMDA receptor antagnoism with **Memantine**, as CNS NMDA-receptor overstimulation by glutamate may contribute to AD Sx.
61
Describe mutation causing Huntington Disease
* Increase in number of **CAG trinucleotide repeats** in the gene that codes for the **huntingtin protein**. Expansion of the protein's polyglutamine region results in a **gain-of-function** that leads to pathological interaction with other proteins, including various transcription factors.
* **Transcriptional repression (silencing)** is one mechanism by which mutated huntingtin is though to cause disease - abnormal huntingtin causes **increased histone deacetylation**, silencing the genes necessary for neuronal survival.
62
How do combination OCP prevent pregnancy?
Inhibit ovulation by decreasing synthesis of FSH adn LH in AP. Their effects on cervical mucus and endometrium play a minor role.
63
On examination, pt leans to right side when walking. When asked to stand on right light, pts left hip tilts downard. Which nerve is injured?
* *Superior gluteal nerve injury** results in weakness and paralysis of the gluteus medius, gluteus minimus, and tensor fasciae latae muscles. These muscles fxn to stablize pelvis and abduct thigh. Weakness of gluteus medius and minimus cause pelvis to sag toward **unaffected (contralateral) side **when patient stands on affected leg (**+ Trendelenburg**). When walking, the patient will lean toward the **affected (ipsilateral)** sid eto compensate for hip drop (**gluteus medius lurch**)
* 1639*
64
Describe S/Sx of femoral nerve damage
Can occur d/t trauma (e.g. pelvic fx), compression from a hematoma or abscess, strength injury, or ischema.
Sx: difficulty with stairs and frequent falling secondary to "knee buckling." Patellar refelx is generally diminished. Sensory loss over anterior and medial thigh and medial leg. Acute, severe pain in groin, lower abdomen, or back may also occur if neuropathy is cuased by retroperitoneal hematoma.
65
Describe characteristics that distinguish between *Strep. pneumoniae* and *Viridans group strep*.
All streptococci are **catalase-negative**. The bile solubility and optochin tests used to differentiate partial (green) hemolytic species (alpha hemolysis). Autolysin produced by S. pneumo is activated by bile, resulting in cell lysis.
Strep pneumo: lancet shaped gram + diplococci, alpha hemolytic, optochin-sensitive, bile-soluble diplococci.
Viridans: gram +, alpha hemolytic, optochin-resistant, bile insoluble.
66
Dsecribe the diagnosis of Cushing syndrome using the dexamethasone suppression test
* Cushing syndrome secondary to adrenal adenoma/carcinoma or exogenous glucocorticoid intake will present with LOW ACTH levels.
* Cushing syndrome caused by pituitary adenoma will present with HIGH ACTH levels that are suppressed by high-dose, but not low-dose dexamethasone.
* Serum ACTH levesl are markedly elevated when there is ectopic ACTCH production by malignatn tumors; even high-dose dexamethasone does not cause suppresion.
67
Describe the function of the HMP shunt and the steps involved
Functions: 1) production of NADPH as a reducing equvalent and 2) synthesis of ribose 5-phosphate for nucleotide synthesis.
Consists of oxidative (irreversible) and non-oxidative (reversible) reactions with all occuring in the cytoplasm.
Oxidative: G6P converted to 6-phosphogluconolactone via G6P dehydrogenase, producing one molecule NADPH (rate-limiting step). Then 6 phosphogluconolactone is hydrolyzed to ribulose 5 phosphate producing a second molecule of NADPH.
68
How do erythrocytes utilize reactions of HMP shunt?
To generate NADPH to maintain glutathione in a reduced state by action of glutathione reductase. **Reduced glutathione** is important in protecting RBCs from oxidative damage.
Oxidative damge to red cells causes denatured hemoglobin to form insoluble **Heinz bodies** resulting in RBC destruction in spleen.
_G6PD deficiency_ is an X-linked disorder that results in episodes of hemolysis during oxidative and infective stress. TMP-SMX has oxidant properties and can precipitate hemolysis in patietns with this disease.
69
Describe the effects of DKA on intra- and extracellular potassium
Lose significant amount of K+ in urine, primarily via glycosuria-induced osmotic diuresis and hypovolemia-mediated increase in aldosterone secretion --\> total body K+ deficit that is reflected by **decreased intracellular K+ stores **
Despite low intracellular K+, **extracellular K+ concentrations are normal or increased** becuase
* loss of intracellular free water caused by increased plasma osmolality leads to extracellular movement of K+ secondary to increasing intracellular [K+]
* lack of insulin causes extracellular shifting of K+ as insulin normally promotes cellular uptake of K+
70
What is the most common presentation of Cryptococcus neoformans infection?
**Meningitis**, whih occurs in immunosupressed patietns and can be diagnosed by **India ink staining** of CSF showing peripheral clearings or "halos" d/t thier thick polysacchardie capsules.
Cryptococcal pneumonia is diagnosed by **mucicarmine staining** (appears red) of lung tissue and bronchoalveolar washings. However, meningitis is more common.
71
Describe the cause and clinical manifestations of Fabry Disease
Inherited deficeincy of **alpha-galactosidase A**, where **globoside cereamide trihexoside** accumulates in tissues.
_Sx_: **hypohidrosis**, **acroparesthesia** (episodic, burning neuropathic pain in extremities), **angiokeratomas** (punctuate, dark red, non-blanching macules and papules that classically occur between umbilicus and knees).
_Prognosis_: without enzyme replacement, progressive renal insufficiency leading to **renal failure and death**.
*1989*
72
What are the two types of vaccines available for S. pneumoniae
* _Pneumococcal polysaccharide vaccine (PPSV23_): capsular material from 23 serotyes. Becuase polysaccharides alone cannot be presented to T cells, the vaccine induces a relatively T-cell-independent B-cell response that is less effective.
* _Pneumococcal conjugate vaccine (PCV13)_: capsular polysaccharides from 13 serotypes that have been covalently attached to recombinant, inactivated diphtheria toxin. Induces active immunity via a T-cell-dependent B-cell response, resulting in improved imunogeniticty d/t formation fo higher affinity antibodies and memory cells.
_Other capsular vaccines_: N. meningitidis, H. influenzae
73
Describe presentation of 11B-hydroxylase deficeincy?
11B-hydroxylase converts 11-deoxycorticosterone to corticosterone and 11-deoxycortisol to cortisol. Deficeincy **prevents synthesis of cortisol and aldosterone** and causes increased production of adrenal adrogens d/t cortisol and aldosterone precursors being diverted toward adreanl androgen biosynthesis.
* Resulting low cortisol stimulate pitutary ACTH production, which further increases adrenal androgens --\> **females with ambiguous genitalia**
* 11-deoxycorticosterone (weak mineralocorticoid) accumulates leading to development of **low-renin HTN and hypokalemia**.
74
Describe the concept of "use dependence" with class 1 antiarrhythmics
These drugs bind to and **block activated and inactivated voltage-gated Na+ channels.** Dissociation of drug from channel occurs during resting state. Use dependence is when tissues undergoing frequent depolarization become more susceptible to blockage (i.e. Na+ channels in rapidly depolarizing tissue spend more time in activated and inactivated states, thus allowing more bindign time for the drug).
Na+ channel binding strength is **1C \> 1A \> 1B**. Use depnedence is much more pronounced with 1C becuase of their slow dissociation from the Na+ channel, which allows their blocking effects to acumulate.
75
How do you calculate Renal Blood Flow (RBF)?
_RBF_ is the volume of blood that flows through the kidney per unit time and is dependent upon the pressure difference between the renal artery and vein, as well as the resistance in renal vasculature.
_RPF_ is the plasma volume that flows through the kidney per unit time.
**RPF = PAH clearence** = (urine [PAH] X urine flow rate) / plasma [PAH]
**RBF** = PAH clearence / (1 - hematocrit)
76
How do NTD occur and how do you test for them?
NTD occur when neural tube fails to fuse in the region of the anterior or posterior neuropores. This leads to persistent communcation between spinal canal and amniotic cavity. Leakage of **alpha-fetoprotein **and **acetylcholinesterase** occurs, which allows for prenatal diagnosis of NTDs.
77
What is the treatment of hyperpyrexia?
Body temperature greater than 40C is called hyperpyrexia and may lead to permanent brain damage if left untreated. Emergent treatment should consist of increasing body heat loss (cooling) and decreasing the hypothalamic set point (antipyretics). **Facilitating body heat loss takes precedence becuase it is effective immediately.**
78
What is the MOA of Zidovudine (AZT)
**Nucleoside reverse transcriptase inhibitor** used in treatment of HIV. Competitively binds to reverse transcriptase and is incorporated into viral genome as a thymidine analog. AZT does not have a 3'-OH group, which is required for new nucleotides to be added to replicating DNA, thus making **3'-5' phosphodiester bond formation impossible**.
79
Describe the histological apperance of psoriasis
* hyperparakeratosis, acanthosis, elongation of rete ridges, mitotic activity above epidermal basal cel layer, and reduced or absent stratum granulosum
* epidermal cel layer superior to dermal papillae may be thinned and contain dilated blood vssels (**Auspitz sign**: pinpoint bleeding when scale is removed from plaque)
* **neutrophils** may form spongiotic clusters in superficial dermis and parakeratotic stratm corneum (**Munro microabscesses**)
80
Whats the cause: facial pain, HA, black necrotic eschar in nasal cavity in a patient with DKA
Highly suggestive of **mucormycosis**, which proliferate in blodo vessels and cause necrosis of downstream tissue. **Histological examination** of the affected tissue is necessary to confirm the diagnosis. These fungi show broad nonseptate hypae with **right angle branching** (helps to distinguish from Aspergillus which can also affect paranasal sinuses of immunosuppressed but are septate hyphae with V-shaped/45 degree branching). Treatment is srugical deridement and **amphotericin B**.
81
Whats the cause, Sx, and histological apperance of abetalipoproteinemia
* AR, LOF mutation in **microsomal triglyceride transfer protein (MTP)**
* Manifests during 1st year of life with Sx of **malabsorption** (abd distention, foul-smelling stool).
* _Lab_: very low TG and cholesterol levels, and chylomicrons, VLDL and apoB are entirely absent.
* Poor lipid absorption causes deficeincy of fat-solbule vitamins (esp. Vit E) and essential FAs resulting in RBC with abnormal membranes and thorny projections (**acanthocytes**) as well as **multiple neurologic abnormalties** (progressive ataxia, retinitis pigmentosa)
* **Enterocytes contain clear or foamy cytoplasm** which is **more prominent at the tips of villi**
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82
Where do anal fissures most commonly occur
**Posterior midline distal to the dentate line**. NOTE that the posterior anal canal is relatively poorly perfused, making its mucosa sensitva to trauma by hard fecal masses.
83
Which region of the bone is affected by hematogenous osteomyelitis?
MC in children and affects **metaphysis** of long bones due to slower blood flow and capillary fenestrae in this region that is conductive to microbial passage. NOTE the vertebral body is the MC location in adults.
Without treatment can progress to **chronic suppurative osteomyelitis**, in which necrotic bone (sequestrum) serves as a reservoir for infection adn becomes covered by a poorly constructed shell of new bone (involucrum).
84
What type of collagen is found in mature scars
The final stage of MI healing process begins 2 weeks after infarction and involves increased type I collagen deposition. Fibrosis continues until about 2m after infaction, resulting in a **dense collagenous scar** composd of **type I collagen**
85
Describe the difference between ischemic preconditioning, myocardial stunning, hibernating myocardium and ventricular remodeling
* A persistent or repetitive low flow state causes **myocardial hibernation** that can be reversed by reperfusion. **Myocardial stunning** ia less severe form of ischemic-induced reversible loss of contractile function.
* Repetitive stunning can result in hibernation. **Ischemic preconditioning** is the development of resistance to infarction by cardiac myocytes previously exposed to repetivie non-lethal ischemia.
* **Ventricular remodeling** involves chronic changes in mass, volume, shape, and myocyte compoistion of the heart, to compensate for increased hemodynamic load.
43
86
What is defined by intermittent muscle pain reproducibly caused by excercise and relieved by a brief period of rest
**Claudication**: result of **atherosclerosis** of larger, named arteries. The obstruction of blood flow d/t fixed stenotic lesions produced by atheromas, which are **lipid-filled intimal plaques** that bulge into the arterial lumen. The stenoses prevent sufficent increases in blood flow to excercising muscle, resulting in inschemic muscle pain.
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87
Describe C. neoformans: morphology, virulence factors, epidemiology, infection, diagnosis, treatment
* _Morphology_: yeast form only; round or oval encapsulated cells with narrow-based buds (**budding yeast**)
* _Virulence factor_: thick polysacchride capsule
* _Epidemiology_: present in soil and pigeon droppings. Opportunistic infectin. Respiratory transmission.
* _Infection_: primary is lung, MC is meningoencephalitis
* _Diagnosis_: India ink stain of CSF, Latex agglutination of CSF, Culture (Sabouraud's agar), Methenamine (GMS), mucicarmine stains of tissue
* _Treatment_: Amphotericin B and flucytosine (acute meningitis). Fluconazole for lifelong prophylaxis
88
How do you calculate absolute risk reductions (ARR)
**ARR** = Event rate in control group - Event rate in treatment group
**ER (treatment group)** = Number of events in treatment arm / Number of subjects in treatment arm
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What are the major adaptive immune mechanisms that prevent reinfection with influenza?
**anti-hemagglutinin IgG antibodies in circulation** and **mucosal anti-hemagglutinin IgA antibodies **in the nasopharynx
90
Describe the manifestation of selective IgA deficiency
**Recurrent sinopulmonary and GI tract infections** due to the abscence of secretory IgA. It is also associated with **anaphylactic response to transfused blood products** due to an immune response against transfused IgA which the patient's body recognizes as foreing.
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What is the most common presentation of Meckel diverticulum?
* **Lower GI bleeding**! The diverticulum often contains **ectopic gastric mucosa** which produces acid causing possible ulceration and bleeding. **99mmTc-pertechnetate scan** identifies ectopic gastric epithelium and helps in diagnosis.
* In addition to melena, can cause **RLQ pain** (challenging to differentiate from acute appendicitis). Can predispose to **intussusception**.
* Occurs due to failure of obliteration of the **omphalomesenteric duct.**
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45 y/o man unable to void and complains of full bladder sensation. Resistance and pain encountered upon trying to place Foley catheter. CT shows pelvic fracture. Pt most likely has injury involving which portions of urogenital tract?
* The **presence of pelvic fx** and **inability to void despite sensation of a full bladder** is suggestive of urethral injury. Additional signs of urethral injury include **presence of blood at urethral meatus** and **high-riding, boggy prostate** (d/t hematoma formation below the gland).
* If urethral injury suspected, **placement of Foley cath is CI**.
* _Posterior urethra_: located above bulb of penis; divided into prostatic and membranous segments. **Membranous segment i**s relatively unsppoorted by adjacent tissue and is weakest point of posterior urethra. **Pelvis fx often results in disruption of posterior urethra at bulbomembranous jxn. **
* _Anterior urethra_: located within bulb and remainder of corpus spongiosum; divided into bulbous (straddle injury such as falling on crossbar of a bicycle) and penile (penetrating trauma or instrumentation) segments
## Footnote
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Describe the consequences of pyruvate dehydrogenase deficeincy and the diet that is recommended for these patients
By preventing the conversion of pyruvate to acetyl CoA, pyruvate is shunted to lactic acid resulting in **lactic acidosis** in these patients.
AA catabolism results in formation of intermediates that are either **glucogenic** (producing intermediates of CAC or pyruvate) or **ketogenic** (producing acetoacetate or its precursors).
* **Ketogenic diet is recommended**. **Lysine** (essential AA) and **leucine** are exclusively ketogenic and would not lead to increased formation of lactic acid.
* Phenylalanine, isoleucine, and tryptophan are both glucogenic and ketogenic.
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A patient has **anemia, an elevated LDH, and an indirect billirubinemia**. There is also **lysing of blood cells when incubated in hypotonic saline**. Whats the diagnosis and what does this patient have the highest risk of developing?
**Hereditary spherocytosis**
* AD condition that results from RBC cytoskeleton abnormalities; MC spectrin and ankyrin defects.
* Dx is with **positive osmotic fragility test**
* **Pigmented gallstones** are a complication of any hemolytic anemia. In chronic hemolysis, the increased bilirubin from lysed RBC precipitates as calcium bilirubinte, forming pigmented stones in the gallbladder.
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A grap shows the SI bicarbonte concentration increasing in association with increasing serum concentrations of an uknown hormone A. The hormone studied is most likely...
**Secretin** is a hormone produced by **S endocrine cells** **in the duodenum** that **increases bicarbonate secretion** from the exocrine pancreas into the small bowel. The release of gastric HCl into the duodenum is the most potent stimulus for S cell secretin release.
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What are circumstances in which minors do not require parental consent?
* Emergency care
* Prenatal care
* Diagnosis or treatment of STDs
* Contraception
* Drug/EtOH rehabilitation
97
Budding yeast and pseudohyphae on light microscopy and a positive germ tube test (blood cultures incubated for 3 hours at 37C/98.6F) are diagnostic of what infection?
Candida albicans. Growing hyphae are called "germ tubes"
## Footnote
*109*
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38 y/o M with long hx of pain and stiffness in both shoulders and knees. Brown spots on sclerae and diffuse darkening of helix of ears. Whats diagnosis and cause?
**_ALKAPTONURIA_**: benign childhood disorder that matures to arthritis in adult life.
* AR; d/t **deficiency of enzyme homogentisic acid oxidase**, which normally breaks down the tyrosine byproduct homogentisic acid (also called alkapton) into maleylacetoacetate.
* Accumulated homogentisic acid causes** pigment deposits in CT throughout body** which become apparent on the **sclera and ear cartilage** during adulthood. Deposits also occur in large joints and spine, causing ankylosis and motion restriction.
* **Urine turns black** when exposed to room air.
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Describe the hormones that use Gs
**Protein kinase A** is primarily responsible for the intracellular effects of the G-portein/AC second messenger system. Some hormoen receptors that use this mechanism include **TSH, glucagon, PTH, and beta-adrenergic receptors. **
994
100
What are alveolar cells containing golden cytoplasmic granules that turn dark blue with Prussian blue staining.
Golden yellow or brownish cytoplasmic granules may be either lipofuscin or hemosiderin. The Prussian blue stain, which detects intracellular iron, is specific for **hemosiderin**.
Increased intravascular pressure in pulmonary capillary bed causes iron-containing proteins and erythrocytes to be extravasated into alveoli. After leaking from congested capillaries, they are phagocytosed by macrophages and converted to hemosiderin. **Hemosiderin-containing alveolar macrophages** ("siderophages" or "HF cells") indicate that epsidoes of pulmonary congestion and edema associated with **left sided heart failure** occured.
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Where are muscarinic receptors and what is the effect of binding of a muscarinic agonists
Although the walls of peripheral blood vessels do not have cholinergic innervation, muscarinic receptors are present on the **endothelial surface**. Binding of cholinomimetic agents promotes release of **NO, also called endothelium-derived relaxing factor (EDRF)**. NO activates guanylate cyclase and increases intracellular cGMP, which activates a Ca pump and causes Ca efflux form cells. A decrease in [Ca+] concentration causes vascular wall smooth muscle relaxation.
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What is the clinical traid of congenital rubella and what is the recommendation for prevention
Traid of congential cataracts (white pupils), sensory-neural deafness, and patent ductus arteriosus.
**Live attenuated rubella vaccine** is recommended for children and non-pregnant women of childbearing age who lack serum antibody.
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An infant born with oral thrush, interstital pneumonia, and severe lymphopenia during first year of life could have been prevented with what?
Consistent with vertical transmission of HIV-1 from mother to fetus. Maternal prophylaxis during pregnancy with the nucleoside analog **zidovudine** (ZDV, AZT), a retroviral reverse transcriptase inhibitor, reduces the risk of perinatal transmission by 2/3 in HIV+ women who have not previously recieved antiretroviral therapy.
104
Describe characteristics of drugs that affect volume of distribution
TBW = 41 L
EFV = 14L (1/3 TBW) with plasma volume about 3L and interstital fluid makes up rest.
Initially drug enters plasma compartment by IV route.
**If the drug has a high MW, highplasma protein binding, or is highly charged (hydrophilic), then the drug generally remains in plasma compartmetn is Vd is low (3-5L). **
If the drug has a small MW and is uncharged (hydrophilic or lipophilic) then it can cross cell membranes and reach intracellular compartment and has a high volume of distribution (41 L).
Drugs that are avidly bound in tissues exhibit the highest Vd (often higher than TBW) because they accumulate within cells and maintain low plasma concetrations.
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What drug is used in the treatment of atypical depression
Atypical depression: mood reactivity (improvement in mood in response to something positive), leaden fatigue (arms and legs feel heavy), rejection sensitivity, and reversed vegetative signs of increased sleep and appetite.
MAOIs such as **phenelzine** and **tranylcypromine** can be used in atypical depression or treatment-resistant depression.
106
What is the cause of hepatic encephalopathy
Increased levels of ammonia and other neurotoxins in the circulation that lead to increased inhibitory neurotransmission and impaired excitatory neurotransmitter release. Frequently precipitated by a stressor that alters the ammonia balance (eg GI bleeding, increased dietary protein).
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107
Describe the EKG findings with occlusion of the RCA, proximal LAD and LCX
* _RCA_: transmural ischemia of inferior wall of LV, producing ST elevation in leads **II, III, and aVF** as well as possible **sinus node dysfunction**
* _Proximal LAD:_ anteroseptal transmural ischemia with ST elevations in **V1-V4**
* _LCX_: transmural ischemia of lateral wall of LV, with ST elevations mainly **V5 and V6,** and possibly also I and aVL
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108
What is teh adenoma to carcinoma sequence for colon adenocarcinoma?
* _Progression of normal mucosa to small polyp_: mutation in **APC** tumor suppressor gene (ch. 5) leading to uncontrolled cell proliferation
* _Increase in size of polyps_: mutation of **KRAS** protooncogene that leads to unregulted cell growth
* _Malignant transformation of adenoma into carcinoma_: mutation of **p53** and **DCC**
109
Acute obsturction of the small airways in infants is usually secondary to what?
**RSV bronchiolitis**. **Ribavirin** (nucleoside analog that inhibits synthesis of guanine nucleotides) is an antiviral drug that may be of benefit in children at risk for disease progression.
110
What is the most common cause of adrenal insufficiency
**Depression of the entire HPA axis (low CRH, low ACTH, low cortisol) by glucocorticoid therapy.** **Adrenal crises** (nonspecific signs such as n/v, abd pain, hypotension, tachycardia) can be precipitated in these patients under stressful situations (i.e. infections or surgery) if their glucocroticoid dose is not appropriately increased.
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How do schwannomas present histologically
**Biphasic pattern of cellularity** (Antoni A and B areas) and **S-100 positivity** (indicating neural crest origin; melanoma is also positive). Schwanomas can arise from peripheral nerves, nerve roots, and CN (expect CN II). Acoustic neuromas are the most common type of intracranial schwannoma and are located at cerebellopontine angle of CN VIII (tinnitus, vertigo, sensorineural hearing loss)
112
Describe where the biochemical processes for cellular metabolism occur
B-oxidation of fatty acids, ketogenesis, CAC, part of urea cycle (carbamoyl phosphate synthetase 1 adn ornithine transcarbamoylase) and pyruvate carboxylation ocur exclusively in **mitochondria**.
All reactions of the pentose phopshate pathway (e.g. enzyme transketolas which uses thiamine/vitamin B1 as cofactor) occur in **cytoplasm**.
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Sampling from which colon area is useful in making diagnosis of Hirschsprung disease
Submucosal (Meissner) and myenteric (Auerbach) autonomic plexi are absent in the affected segment of the bowel. The **submucosa of the narrowed area** is the most superficial layer where the abscence of ganglion cells can be seen.
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In early embryonic development, what are the main categories of the bodys veins and what happens to them
**Vitelline**: form veins of portal system
**Umbilical**: degenerate
**Cardal veins**: form veins of systemic circultion. Gives rise to SVC which can be identified on CT as to the right of the heart, posterolateral to ascending aorta, anterior to right pulmonary artery and just below level of carina.
All veins of developing embryo ultimately drain into **sinus venosus**, which itself drains into the primitive atrium of developing herat.
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In the respiratory tract, which regions are lined by pseudostratified columnar mucus-secreting epithelium vs. stratified squamous epithelium?
_Pseudostratified columnar mucus secreting_: nose, paranasal sinuses, nasopharynx, most of larynx, and tracehobronchial tree
_Stratified squamous_: oropharynx, laryngopharynx, anterior epiglottis, upper half of posterior epiglottis, and vocal folds (true vocal cords)
116
What is the cause and presentation of Homocystinuria?
MC inborn error of methionine metabolism d/t **cystathionine synthetase deficiency.** Sx resembling Marfan syndrome, particuarly ectopia lentis (dislocated lens), and many exeprience developmental delay. Also risk of developing thromboembolism. About 50% respond to high doses of **vitamin B6 (pyridoxine)**, which improves residual enzymatic activity and reduces plasma homocysteine levels.
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Describe linkage disequilibrium
When a pair of alleles from two loci are inherited together in the same gamete (haplotype) more or less often than woudl be expected by random chance alone given their corresponding allele frequencies. Note that this can occur even if the genes are on different chromosomes.
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Describe the train-of-four responses for nondepolarizing vs. depolarizing NMJ blocking drugs
The paralytic action of **nondepolarizing NMJ blocking drugs (pancuronium and tubocurarine**; competitive atnagonists at nicotinic ACh receptor) can be reversed by anticholinesterase agents such as neostigmine. Train-of-four responses display a **fading pattern**.
**Succinylcholine** is a **depolarizing NMJ blocker** that is augmented by neosigmine during phase I block but reversed during phase II block. The duration of paralysis depends largely on its catablism by plasma cholinesterase. **Sustained and equal reduction of all 4 twitches during phase I**; continued administration of succinylcholine results in transition to phase II blockade with twitch responses that mimic those of nondepolarizers.
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When a TEE probe is placed within the esophagus, what can be visualized anteriorly and posteriorly
**Anterior = LA**, which forms the majority of the posterior surface of the heart and resides adjacent to the esophagus. Enlargement of the LA (e.g. Afib or mitral stenosis) can compress the esophagus and cause dysphagia.
**Posterior = Descending Thoracic Aorta**
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What is the effect of carbon monoxide on PaO2, Carboxyhemoglobin, and Methemoglobin
CO binds to hemoglobin (carboxyhemoglobin) with much higher affinity than O2, thus preventing oxygen binding to hemoglobin and decreasing the oxygen content of blood. It also reduces oxygen unloading from hemoglobin in the tissues. CO poisoning does not affect the PaO2 (typically normal) and does not precipitate methemoglobinemia.
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Describe the difference in acid base physiology between a pt wtih heroin overdose vs. COPD
Heroin overdose is an aute event; it suppresses respiratory centers and causes hypoventiltion and retention of CO2. Chronic bronchial obsturction wtih long-standing retention of CO2 allows enough time for renal compensation and an increase in serum HCO3.
* Hypoventilation causes an increase in arterial pCO2 and a decrease in serum pH (respiratory acidosis).
* **Acute respiratory acidosis** presents with low pH, high pCO2, and normal to midly increased HCO3 becuase renal compensation requires at least 24h of persistant respiratory acidosis.
* **Chronic respiratory acidosis** is characterized by a low normal pH, a high pCO2, and a high HCO3 (\>30).
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What is the MOA of Colchicine
Sometimes used to treat **acute gouty arthritis** (preferred 1st line is NSAIDs). Works by **inhibition of microtubular polymerization** by binding to the protein subunit of microtubules and preventing thier aggregation. This in turn **disrupts membrane-dependent fxns such as chemotaxis and phagocytosis.** Also **reduces formation of LTB4.** Adverse effects include nausea, abdominal pain, and diarrhea.
123
If energy-dependent organic anion transport across the hepatocellular membrane is selectively inhibited, what would result?
**Increased bilirubin excretion in the urine**
The liver takes up indirect (unconjugated) bilirubin through a passive process and secrets direct (conjugated) bilirubin through an active process. UCB is virtually insoluble in water at physiologic pH and is tightly complexed to serum albumin while in circulation; cannot be excreted in urine. CB is water-solbule, non-toxic and only loosely bound to albumin; can be excreted in urine.
124
What does LH and FSH stimulate the release of in males
LH stimultes release of testosterone from Leydig cells of the testes. FSH stimultes the release of inhibin B from Sertoli cells in the seminferous tubules, and stimulates sertoli cells to produce androgen-binding protein locally which is responsible for the high local [testosterone]. Testosterone and inhibin B induce negative feedback on LH and FSH production, respectively. **Defective FSH receptors will prevent spermatogenesis and cuase low inhibin B levels. **
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What is the most common disorder of the urea cycle and how does it present clinically
**Ornithine transcarbamoylase deficiency**. Results in **severe neuro abnormalities** due to **high blood and tissue ammonia levels.** **Increased urine orotic acid** excretion is typical, as accumulated carbamoyl phosphate is converted into orotic acid.
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What are bisphosphonates structural analogues of?
Structural analogues of **pyrophosphate**, an important component of hydroxyapatite; also decrease boen resorption by interfereing with osteoclasts. These drugs are used in treatmetn of osteoporosis, Paget's, and malignancy-induced hypercalcemia. Administered in fasting state and must stay upright for 30m to prevent reflux esophagitis.
127
What neuroendocrine compensatory mechanisms exacerbate CHF?
CHF leads to decreased CO and inadequate oxygen delivery to tissues. Decreased CO triggers a number of compensatory mechanisms. RAAS activation and increased sympathetic output **raise arterial resistance (afterload)** and exacerbate HF by making it more difficult for the failing heart to pump blood to the tissues.
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Describe how viruses use eukaryotic ribosomes for protein synthesis
Because viruses must use eukaryotic ribosomes for protein synthesis, they must convert thier polycistronic genome into monocistronic mRNA (i.e. final mRNA codes for a single protein product). Some viruses accomplish this through the **production of a polyprotein product** from a single mRNA transcript. This product is later **cleaved by a viral protease** to generate a complete set of functional, individual viral proteins.
Ex: single-stranded, positive-sense, linear, nonsegmented RNA viruses such as **echovirus** (Picornaviridae family)
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How do you calculate incidience of disease
number of cases of a disease per year divided by total population at risk
