Week 3 Flashcards
(162 cards)
1
Q
What are the superficial and deep inguinal rings?
A
They are physiological openings in the external abdominal oblique aponeurosis (superficial) and transversalis fascia (deep).
Surgical repair of an undescended testicle lodged in the inguinal canal involves reducing the testis through the superficial inguinal ring and fixting it in the scrotum (orchiopexy).
Internal spermatic fascia, Cremasteric muscle and fascia, External spermatic fascia (ICE)
Transversalis fascia, Internal oblique, External oblique (TIE)
2
Q
What is multiple myeloma?
A
Presentation: fatigability, constipation, bone pain due to osteolysis, elevated serum protein, renal failure (azotemia - high serum creatinine and BUN)
Pathogenesis: Myeloma cast nephropathy due to excess excretion of free light chains (Bence Jones proteins). Light chains precipitate with Tamm Horsfall protein and form casts that cause tubular obstruction and epithelial injury.
Microscopy: glassy casts stain intensely eosinophilic, composed of bence jones proteins
3
Q
What vitamins are inadequate in breastmilk?
A
Vitamins D and K.
Vitamin K is given parenterally to all newborns at birth to prevent hemorrhagic disease of the newborn.
Exclusively breastfed infants require vitamin D supplementation due to lack of sunlight exposure and to prevent rickets.
4
Q
What is temporomandibular disorder (TMD)?
A
Presentation: unilateral facial pain that worsens with jaw movement, HA, and ear discomfort;
Mandibular nerve of trigeminal nerve: supplies sensation to the temporomandibular joint, motor fibers to muscles of mastication, tensor veli palatini and tensor tympani in middle ear
5
Q
What are the effects of aging on lung volumes?
A
Decreases in chest wall compliance; decrease in forced vital capacity, inspiratory reserve volume, vital capacity, expiratory reserve volume
Increases in lung compliance due to loss of elastic recoil; increase in residual volume (due to air trapping), functional residual capacity
Unchanged: total lung capacity
6
Q
What is dermatomyositis?
A
Pathogenesis: systemic autoimmune disease; affects the muscles and skin
Presentation: proximal muscle weakness resembling polymyositis, but with additional inflammatory features involving the skin (heliotrope rash in peri-orbital area and cheeks), Gottron’s papules (raised erythematous plaques over the joints and bony prominences of the hands); shawl and face rash; darkening and thickening of fingertips/sides (appear “dirty”)
Muscle biopsy dx: mononuclear perimysial infiltrates (CD4), perifascicular atrophy, patchy necrosis
Labs: anti ANA, anti Jo1 (histidyl tRNA synthetase), anti SRP, anti Mi2; increased CK
Strong association with non-hodgkin lymphoma, lung, ovarian, and colorectal cancer (adenocarcinomas)
Tx: steroids, followed by long-term immunosuppressant therapy (e.g., methotrexate)
7
Q
What is the S4 heart sound?
A
Low frequency sound heard at the end of diastole just before S1.
Pathogenesis: due to decreased LV compliance, often associated with restrictive cardiomyopathy and LVH; the louder the sound, more likely due to pathologically stiff LV
Benign in older adults, always pathologic in younger patients.
8
Q
What is the process of wallerian degeneration in the CNS?
A
Wallerian degeneration refers to the process of axonal degeneration and breakdown of the myelin sheath that occurs distal to a site of injury.
CNS: macrophages recruited slowly due to BBB; oligodendrocytes become inactive/apoptose and do not assist with phagocytosis; slow removal of myelin debris which can persist for years and suppresses axonal growth via myelin assoc. inhibitory factors
Axonal reaction = changes seen in neuronal body after axon is severed; cell body shows signs of cellular edema; becomes swollen and rounded w/ nucleus displaced to periphery; Nissl substance becomes fine, granular and dispersed throughout cytoplasm (central chromatolysis); changes reflect an increased synthesis of protein by cells in order to regenerate severed axon
PNS: Schwans cells degrade myelin, secrete cytokines and chemokines rthat recruit macrophages; effective clearance of myelin debris, facilitates nerve regeneration
[Irreversible injury: shrinkage of neuronal body, deep eosinophilia of cytoplasm, pyknosis of nucleus and loss of Nissl substance.]
9
Q
What is blastomyces dermatiditis?
A
Epidemiology: OH and MS River valleys, Great lakes region; found in soil
Presentation: pulmonary (pneumonia); disseminated form is common and severe
Lab dx: culture at 25C: branching hyphae
Biopsy: large, round yeasts with doubly refractile wall and single broad-based bud
10
Q
What is paracoccidiodes brasiliensis?
A
Epidemiology: Central and South America
Presentation: Mucocutaneous - chronic mucocutaneous or cutaneous ulcers, can progress to lymph nodes and lungs
Lab dx: culture at 25C - multiple blastoconidia;
Biopsy: cells covered in budding blastoconidia
11
Q
What is the MOA of nitrates?
A
They dilate the veins >> arteries, reduce preload; decreases LV end-diastolic volume and wall stress resulting in decreased myocardial oxygen demand and relief of angina symptoms.
Sublingual nitroglycerin is used for rapid symptom relief in patients with stable angina.
12
Q
What are the effects of a 21 hydroxylase deficiency?
A
Decrease in cortisol and aldosterone
Increase in testosterone and 17 hydroxyprogesterone
Sx: ambiguous genitalia in girls; salt wasting (vomiting, hypotension, decrease in Na, increase in K)
13
Q
What are the effects of an 11Beta hydroxylase deficiency?
A
Decrease in cortisol and aldosterone
Increase in testosterone, 11-deoxycorticosterone (weak mineralocorticoid) and 11-deoxycortisol
Sx: ambiguous genitalia in girls, fluid and salt retention, hypertension
14
Q
What are the effects of a 17alpha hydroxylase deficiency?
A
Decrease in cortisol and testosterone
Increase in mineralocorticoids and corticosterone (weak glucocorticoid)
Sx: all patients phenotypically female, fluid and salt retention, hypertension
15
Q
What is a complete mole?
A
A complete hydatidiform mole results when an empty ovum is fertilized by a haploid sperm. Susequent duplicationi of the paternal genetic complement (23x) results in 46,XX genotype (90% of the time).
16
Q
What happens due to blockage of the splenic artery?
A
The splenic artery originates from the celiac artery and gives off branches to the stomach and pancreas (pancreatic, short gastric, left gastroepiploic arteries) before reaching the spleen.
Due to poor anastomoses, the gastric tissue supplied by the short gastric arteries is vulnerable to ischemic injury following splenic artery blockage.
17
Q
What is the #1 recommended lifestyle modification for patients with diabetes?
A
Smoking cessation is the most effective prevention intervention in almost all patients, especially those with diabetes.
18
Q
What is depersonalizaton/derealization disorder?
A
Persistent or recurrent experiences of 1 or both:
Depersonalization: feelings of detachment from, or being an outside observer of, one’s self)
Derealization: experiencing surroundings as unreal; sense of detachment or unreality
[Intact reality testing.]
19
Q
What is dissociative amnesia?
A
Inability to recall important personal information, usually of a traumatic or stressful nature
Not explained by another disorder (e.g., substance use, post-traumatic stress disorder)
20
Q
What is dissociative identity disorder?
A
Marked discontinuity in identity and loss of personal agency with fragmentation into > or equal to 2 distinct personality states.
Associated with severe trauma/abuse.
21
Q
What is lateral medullary (Wallenberg) syndrome?
A
Ischemia of the posterior inferior cerebellar artery (PICA; a branch of the vertebral artery)
Presentation:
Bulbar weakness (dysphagia, dysphonia); decrease gag reflex, hiccups due to injury of nucleus ambiguus (CN 9, 10, 11)
8: vomiting, vertigo/nystagmus due to damage of the vestibular nucleus
5/STT: Loss of pain/temp sensation in ipsilateral face and contralateral body (spinal trigeminal nucleus and spinothalamic tract)
Ipsilateral cerebellar signs (ataxia w/ tendency to fall toward side of lesion) due to injury to inferior cerebellar peduncle
Ipsilateral Horner syndrome due to damage of sympathetic fibers innervating head
22
Q
What is acute compartment syndrome?
A
Pathogenesis: caused by increased pressure w/in fascial compartments of limbs leading to impaired perfusion.
Presentation: severe pain, myonecrosis, nerve injury
Anterior compartment of leg: anterior tibial artery; deep peroneal (fibular) nerve; most common site of ACS; leads to decreased sensation between first and second toes, decreased dorsiflexion of foot, foot drop, and claw foot
Lateral compartment: superficial peroneal nerve
Deep posterior compartment: tibial nerve
23
Q
What is cystinuria?
A
Autosomal recessive disorder; caused by defective transportation of cystine, ornithine, arginine, and lysine (COLA) across the intestinal (absorption) and renal tubular epithelium (reabsorption).
Presentation: recurrent nephrolithiasis is the only clinical manifestation
Urinalysis shows pathognomic flat yellow, hexagonal cystine crystals.
24
Q
What is pertussis?
A
Whooping cough; highly contagious; transmitted via respiratory droplets
Dx should be considered in any adult with acute tracheobronchitis who has not had vaccination boosters.
Pathogenesis: caused by gram-negative coccobacillus, Bordetella pertussis.
Presentation: paroxysmal cough lasting >2w that is assoc. with post-tussive emesis or inspiratory whoop after a severe coughing episode.
25
What is the mechanism of antibiotic resistance against cephalosporins?
A change in the **structure** of penicillin-binding proteins that prevents cephalosporin binding.
26
What is succinylcholine?
A fast acting, depolarizing neuromuscular blocking agent used for rapid sequence intubation that causes equal reduction of all 4 twitches during train of four stimulation (flaccid paralysis; phase I blockade).
Prolonged administration of succinylcholine or use in patients with abnormal plasma cholinesterase activity causes transition to a phase II (nondepolarizing) block, seen as a progressive reduction in each of the 4 twitches. Continuous depolarization gives way to gradual repolarization as nAchR becomes desensitized to effects of succinylcholine.
nAchR is nonselective cation channel: allows Na influx and K efflux.
Adverse effecs of succ: malignant hyperthermia; severe hyperkalemia in pts with burns, myopathies, crush injuries, and denervation, bradycardia from parasympathethic stimulation or tachycardia from sympathetic effects
27
What are migraines headaches?
Presentation: unilateral, pulsating or throbbing; associated with photophobia, phonophobia and nausea
Pathogenesis: activation of trigeminal afferents that innervate the meninges; causes release of vasoactive peptides (substance P and calcitonin gene related peptide) which results in neurogenic inflammation due to vasodilation and plasma protein extravasation
Tx: triptans; serotonin **5HT1B** (inhibits release of SE) **and 5HT1D** (vasoconstricts) **agonists** are used as abortive therapy; they **inhibit release of vasoactive peptides**, promote **vasoconstriction**, and block pain pathways in brainstem
Prophylaxis: Beta blockers, antidepressants (e.g., amitriptyline and venlafaxine) and anticonvulsants (e.g., valproate and topiramate)
28
What is the granulosa cell tumor of the ovary?
Pathogenesis: tumor derived from ovarian stroma; sex cord stromal tumor; contains granulosa cells and some theca cells
Presentation: unilateral and large tumor; **secretes estrogen** and can present with **endometrial hyperplasia**; increase in inhibin
Histology: **Call-Exner bodies** - cells grow in cords or cuboidal sheets, and form microfollicular or rosette like structures that have a **gland-like** appearance with a pink eosinophilic/acidophilic center and coffee bean nuclei
Gross: **theca cells** are plump with **lipid contents**, which give the **mass a yellow color**
29
Where are the parietal cells and chief cells located in the stomach?
Parietal cells: oxyntic (pale pink); found predominantly in the upper glandular layer of gastric body and fundus
Chief cells: basophilic, granular; found in the deeper region of the gastric glands
30
What is cytokeratin? Vimentin? Chromogranin A? Synaptophysin?
**Keratin**: Immunohistochemical marker of epithelial cell carcinomas.
Proteins that help form the keratin-containing intermediate filaments that make up cytoskeleton of almost all epithelial cells.
**Vimentin**: intermediate filament present in **mesenchymal tissue**; used to detect sarcomas
**Chromogranin A and synaptophysin**: used for **neuroendocrine** tumors
31
What is Brown Séquard syndrome?
Pathogenesis: hemisection of the spinal cord
Presentation:
Anterior horn injury (lower motor neuron) - **ipsilateral** flaccid paralysis at the level of the lesion
Lateral corticospinal tract (upper motor neuron) - **ipsilateral** loss of touch, vibratory sensation, and propioception below level of the lesion
Damage to lateral spinothalamic tract - **contralateral** loss of pain and temperature sensation 1-2 levels below the lesion
Spinal cord injury above T1 can also cause ipsilateral Horner syndrome (ptosis, miosis, anhidrosis) if there is concurrent damage to oculosympathetic pathway.
32
What are reticulocytes?
Immature RBC that are slightly larger and bluer than a mature RBC.
Lack a cell nucleus but retains a **basophilic**, reticular (mesh-like) network of **residual ribosomal RNA**. The ribosomal RNA appears blue microscopically after application of Wright-Giemsa stain.
33
What is surfactant?
**Phosphatidylcholine (lecithin; L)** and phosphatidylglycerol are major components of pulmonary surfactant and **sphingomyelin (S)** is a common membrane phospholipid.
Lecithin production increases sharply after 30w gestation; phosphatidylglycerol production increases at 36w. Sphingomyelin levels remain constant during the 3rd trimester.
An **L/S ratio \> or equal to 2** indicates adequate surfactant production to avoid neonatal hyaline membrane disease.
34
What are the symptoms of hypoglycemia?
**Neurogenic** (autonomic): sx caused by sympathoadrenal activation; mediated via NE/E and Ach released by sympathetic postganglion;
NE/E sx - tremulousness, palpitation, anxiety/arousal;
Ach sx - sweating, hunger, paresthesias
**Neuroglycopenic:** sx include visual disturbances, seizures, confusion, stupor, behavioral changes
Non-selective Beta-blockers (propanolol, timolol, nadolol) inhibit NE/E mediated compensatory reaction to hypoglycemia (cholinergic sx are unaffected); inhibit hepatic gluconeogenesis and peripheral glycogenolysis and lipolysis; can increase risk of hypoglycemia, **masks the adrenergic sx mediated by NE and E**; pts are unaware of hypoglycemia
Selective B1 and B blockers w/ instrinsic sympathomimetic activty (pindolol, acebutolol) are preferred for diabetics; have minimal effect on glucose metabolism and adrenergic sx
35
What is a septic abortion?
Any type of abortion resulting in infected retained products of conception in uterine cavity.
Pathogenesis: gram-negative bacilli (**e. coli**); **s. aureus** (very common); group b strep due to seeding of uterine cavity during instrumentation
Presentation: fever, abdominal pain, uterine tenderness, foul-smelling vaginal discharge after pregnancy termination
Long term complication: sepsis, multiorgan failure, synechiae (adhesions) in uterine cavity that lead to secondary amenorrhea and infertiity (Asherman syndrome)
Tx: broad-spectrum antibiotics; prompt surgical evacuation
36
What are the different types of collagen?
**Type 1:** dermis, bone, tendons, ligaments, dentin, cornea, blood vessels, and mature **scar tissue**; assoc. disease - osteogenesis imperfecta
**Type 2**: cartilage, vitreous humor and nucleus pulposis
**Type 3:** skin, lungs, intestines, blood vessels, bone marrow, lymphatics, and **granulation tissue**; assoc. disease - Ehlers Danlos syndrome (Types 3 and 4)
**Type 4:** basement membranes; assoc. disease - Alport Syndrome
37
How is calcium regulated in a cardiac muscle cell? Smooth muscle cell?
Cardiac: L type Ca2+ channels permit influx of Ca
**Ryanodine receptor** releases Ca via calcium induced calcium release
**Na-Ca exchanger** and sarcoplasmic reticulum Ca2+ ATPase (SERCA2) pump remove Ca from cells prior to relaxation;
Smooth muscle: lack troponin so **calmodulin** is important for excitation-contraction coupling;
38
What is giant cell (temporal) arteritis?
Pathogenesis: cell-mediated immunity is the primary mechanism underlying giant cell arteritis in medium to smaller branches of carotic artery; production of **IL6 is important driver**
Presentation: \>50yo; jaw claudication, headaches, visual and muscular symptoms (polymyalgia rheumatica); confers high risk of thoracic aortic aneurysms
Histology: granulomatous inflammation centered on media w/ intimal thickening, elastic lamina fragmentation, and giant cell formation
Labs: increased **ESR or C-reactive protein**
DX: temporal artery biopsy, intimal thickening, elastic lamina fragmentation, multinucleated giant cells
Tx: monoclonal antibody against IL6 (tocilizumab); **glucocorticoids**
39
What is osteogenesis imperfecta?
Pathogenesis: Autosomal dominant; impaired synthesis of **osteoid** (organic portion of bone matrix which is made of type 1 collagen) by osteoblasts
Presentation: brittle bones prone to fracture with minimal trauma; blue sclerae due to deficient connective tissue; small, malformed teeth; joint laxity; susceptibility to bruising and hearing loss
40
What is the effect of estrogen on thyroid hormones?
An increase in E increases the level of thyroxine-binding globulin.
This leads to an increases in total TH levels, but feedback control maintains normal levels of free (biologically active) TH.
Level of free TH remains normal, patients remain euthryoid, and TSH levels return to the normal range.
41
What is etoposide?
It targets **topoisomerase II.**
Irinotecan and topotecan inhibit topoisomerase I.
Topo I: single-stranded nicks to relieve negative supercoiling
Topo II: breaks in both DNA strands to relieve positive and negative supercoiling
42
What is primary hyperaldosternonism?
Pathogenesis: unilateral adrenal adenoma (**Conn** **syndrome**) and bilateral adrenal hyperplasia; aldosterone-producing adenoma
Presentation: hypertension, hypokalemic alkalosis (_**muscle** **weakness**, **paresthesias**_);
Histology: adrenocortical adenomas appear as well-defined **yellowish** tumors of adrenal cortex on gross examination, regardless of functional status
Labs: increased Na reabsorption, increased excretion of K and H leading to hypokalemia and metabolic alkalosis; **plasma renin is suppressed** due to hypertension/high blood volume; elevated plamsa aldosterone, aldosterone **remains elevated** following oral saline load
Aldosterone escape: increased intravascular volume causes increasd renal blood flow (w/ resulting pressure natriuresis) and release of ANP; limits net Na retention; so Na is normal
43
What is sarcoidosis?
Epidemiology: young adults; African American females
Pathology: biopsy showing n**on-caseasting granulomas** that stain negative for fungi and acid fast bacilli; granulomas produce _ACE and 1,25 Vitamin D_ (1-alpha hydroxylase in macrogphages); accumulation of **CD4 T cells** drive granuloma formation; high **CD4/CD8** ratio in bronchoalveolar lavage fluid
Presentation: cough, dyspnea; chest pain; erythema nodosum (subcutaneous nodules), arthralgia; **scattered granulomas** are common liver pathology finding
Assoc. w/: bell palsy, uveitis, lupus pernio
Imaging: **_bilateral hilar adenopathy_;** _pulmonary reticular infiltrates_
Labs: hypercalcemia/hypercalciuria; **_elevated serum ACE_**
Tx: steroids if symptomatic
44
What does the suffix of a biological agent indicate?
Mab: monoclonal antibody
Cept: receptor molecule
Nib: kinase inhibitor
45
What is vitamin K deficiency?
Vit. K is a cofactor for gamma glutamyl carboxylase, which carboxylates Factors 2, 7, 9, and 10.
Pathogenesis: low vitamin K in breast milk, refusal of vit K prophylaxis at birth; patients with CF are at risk for deficiency due to malabsorption of fat soluble vitamins
Presentation: life-threatning bleeding diathesis (intracranial hemorrhage, profuse bleeding from GI tract, umbilicus, and surgical sites)
Presentation in neonates: intracranial hemorrhage is a complication presenting with signs of increased intracranial pressure (altered mental status, **enlarged** **head** **circumference**, **bulging** **fontanel**, **downward**-**driven**"**sunset**" eyes)
Tx: Intramuscular supplementation at birth
46
What is renal ammoniagenesis?
Metabolic acidosis stimulates renal ammoniagenesis, a process by which renal epithelial cells metabolize glutamine to glutamate, generating ammonium and bicarbonate.
Ammonium ions are transported into tubular flluid and excreted in the urine as NH4+.
Peritubular capillaries absorb bicarbonate, which functions to buffer acids in the blood.
47
What are the paramesonephric ducts?
In females, they fuse to form the fallopian tubes, uterus, cervix, and upper vagina.
Disruptions lead to mullerian tract anomalies: incomplete lateral fusion can result in bicornate uterus characterized by indentation in the center of fundus; renal anomalies are common comorbidity
48
What are the adverse side effects of psychostimulants (methylphenidate and amphetamines)?
Decreased appetite, weight loss, and insomnia.
49
How doe the cephalic, gastric, and intestinal phases influence gastric acid secretion?
Cephalic: mediated by cholinergic and vagal mechanisms (triggered by thought, sight, smell, and taste of food)
Gastric: mediated by presence of gastrin (which stimulates histamine secretion and therefore acid secretion); triggered by chemical stimulus of food and distension of stomach
Intestinal phase: initiated when protein-containing food enters duodenum (minimal role in stimulating gastric acid secretion); more effective in down-regulating gastric acid secretion after meal - ileum and colon release **peptide YY** inhibiting gastrin-stimulated histamine release from enterochromaffin cells
Other inhibitors of acid secretion: somatostatin and prostaglandins
50
What are the 3rd and 4th heart sounds?
**S3**: ventricular gallop sound (after S2); heard during **forceful** **rapid passive filling** of ventricles in diastole (exceeds expansion capacity) and leads to sudden cessation of filling as ventricle reaches elastic limit; associated with **systolic HF/volume overload**; **MR**, **high-output states**; i**ncreased LVEDV**; normal in \<40yo, pregnancy; heard in settings causing high **ventricular filling pressures** and/or vol. overload **(AR, MR, dilated cardiomypathy)**
**S4**: atrial gallop sound (before S1); heard immediately after atrial contraction as blood is forced into a **stiff ventricle**; assoc. w/ younger adults/children, **diastolic dysfunction** (e.g., LVH); normal in older adults
Left ventricular gallops (S3 and S4) are best heard with the bell of the stethoschop over the **cardiac apex** while the patient is in the **left lateral decubitus position** at the **end of expiration** (lung volume decreases and brings the heart closer to the chest wall).
51
What kinds of cells does HPV infect?
Human papilloma virus (HPV) is a small dsDNA virus with a tropism for **stratified squamous epithelium**, which protectively lines areas that undergo frequent friction and abrasion (**true vocal cords** - only area in respiratory tract covered with it, cervix, and anus).
Infants can acquire respiratory papillomatosis via passage through an HPV infected birth canal.
52
What is vitamin A toxicity?
Presentation: intracranial hypertension, skin changes (dry skin), hepatosplenomegaly.
53
What is vitamin B12 deficiency?
Pathogenesis: associated with pernicious anemia
Presentation: older, mentally slow woman of northern European descent who is "lemon colored" (anemic and icteric); smooth, shiny tongue indicative of atrophic glossitis; shuffling broad based gait
54
What impacts the power of a study?
Power = 1-Beta; the probability of a type II (beta) error is related to how much power a study has to detect a difference when a difference actually exists.
A study's power increases as its sample size increases. The larger the sample, the greater the ability of a study to detect a difference when one truly exists.
55
What is synovitis?
Presentation: pain, erythema, swelling, reduced range of motion in a joint
Acute synovitis may represent serious pathology (e.g., septic arthris) especially if accompanied by **fever or leukocytosis**;
It should be evaluated with **synovial analysis** for crystal analysis, cell count, gram stain, and culture.
56
What is the position of the ureter with respect to the gonadal vessels, the internal iliac artery and uterine artery?
The ureter passes under the gonadal vessels (retroperitoneum) and uterine arter (water under the bridge).
The ureter passes over the internal iliac artery and medial to ovarian vessels, in the true pelvis.
57
What is polycystronic mRNA?
One mRNA codes for several proteins.
Ex: the bacterial lac operon, which codes for proteins for lactose metabolism by e. coli;
The transcription and translation of the bacterial proteins is regulated by a single promoter, operator, and set of regulatory elements.
58
What is paraneoplastic cerebellar degeneration?
Pathogenesis: autoimmune; immune response against tumor cells that cross reacts with Purkinje neuron antigens, leading to acute onset rapid degeneration of cerebellum
Presentation: progressively worsening **dizziness, limb and truncal ataxia**, **dysarthria, and visual disturbances**; assoc. with **small cell lung cancer**, as well as breast, ovarian, and uterine cancers
Serum: anti-yo, anti-P/Q, and anti-Hu antibodies
59
What are the antibodies in the serum of the different blood groups?
A: Anti B (IgM)
B: Anti A (IgM)
AB: none
O: Anti A and Anti B (IgG); can cross the placenta to cause fetal hemolysis
60
What is a zenker diverticulum?
Pharyngoesophageal false diverticulum, herniation through zone of muscle weakness in posterior hypopharynx
Pathogenesis; abnormal spasm or diminished relaxation/herniation of the mucosal tissue at Killian triangle between thryopharyngeal and cricopharyngeal parts of inferior pharyngeal constrictor
Presentation: elderly; males; oropharyngeal dysphagia (feeling of food obstruction at level of neck); esophageal dysmotility/dysphagia, halitosis, regurgitation, recurrent aspiration, neck mass
61
What is an arcuate scotoma?
Occur due to damage to a particular region of the **optic nerve head**.
Resulting visual field defect follows the arcuate shape of the nerve fiber pattern.
62
What is gestational choriocarcinoma?
Pathogenesis: malignant tumor that arises from trophoblast
Presentation: abnormal vaginal bleeding, uterine enlargement; dyspnea/hemoptysis due to **pulmonary metastasis** from hematogenous spread; **lungs are most common site of distals mets**
Microscopy: Bulky mass; soft yellow-white, areas of necrosis and hemorrhage; no villi are present
Histology: abnormal proliferation of anaplastic mononuclear cytotrophoblasts and mutlinuclear synctiotrophoblasts
Labs: increased Beta hCG
63
What is the MOA of ribavirin?
Causing defective 5'cap formation on viral mRNA transcripts --\>inefficient viral translation
Inhibiting viral RNA polymerase and inosine monophosphate dehydrogenase (depleting GTP)
Lethal hypermutation --\>defective HCV virions
Enhances Th1 cell mediated immunity, inhibits Th2 cytokine production to modulate more effective immune response
64
What is derived from each branchial and aortic arch (vessels)?
1: CN 5.3; maxillary artery (bones: maxilla, mandible, malleus, incus, zygoma, sphenomandibular ligament; muscles of mastication, anterior belly of digastric, tensor tympani, tensor veli palatini)
2: CN 7; hyoid artery, stapedial artery (regresses) (bones: styloid process of temporal bone, lesser horn of hyoid, stapes, stylohyoid ligament; muscles of facial expression, stapedius, stylohyoid, platysma, posterior belly of digastric)
3: CN 9; common carotid artery, proximal internal carotid artery (bones: greater horn of hyoid; stylopharyngeus)
4: Superior laryngeal branch of CN X; true aortic arch on the L, proximal subclavian arteries on the R (bones: arytenoids, cricoid, corniculate, cuneiform, thyroid; muscles - pharyngeal constrictors, cricothyroid, levator veli palatini)
5: obliterated for both
6: Recurrent/inferior laryngeal branch of CN X; pulmonary arteries, ductus arteriosus (bones: arytenoids, cricoid, corniculate, cuneiform, thyroid; muscles - all intrinsic muscles of larynx except cricothyroid)
65
What is rheumatic fever?
Pathogenesis: immune-mediated complication of untreated group A strep pharyngeal infection
Presentation: fever, fatigue, anorexia; mitral regurgitation (holosystolic murmur)
Histology: interstitial myocardial granuloma (Aschoff body), which contains Anitschkow cells (macrophages with abundant cytoplasm and central, slender chromatin fibers)
Incidence reduced with prompt treatment of streptococcal pharyngitis with penicillin (penicillin will not reduce risk of PSGN)
66
How is coronary blood flow dominance determined?
Coronary dominance is determined by the coronary artery supplying the posterior descending artery (PDA), which also supplies blood to the AV node via the AV nodal artery. The AV nodal artery arises from the dominant coronary artery.
70% of PDA: comes from RCA, right dominant
20% of PDA: both the rCA and LCX
10% of PDA: LCX, left dominant circulation
67
What is the impact of vasopressin on urea transporters?
Vasopressin activates urea transporters in the medullary collecting duct, increasing urea reabsorption and decreasing renal urea clearance. This enhances the medullary osmotic gradient, allowing the production of maximally concentrated urine.
68
What is conversion disorder?
A somatic symptom disorder characterized by symptoms or deficits of **voluntary motor and/or sensory function** that are **incompatible** with any recognized neurological condition and **cannot** be explained by another medical or mental disorder. Often follows an acute stressor.
Patient has incongruous laack of concern about symptoms - should not be used to make dx.
69
What are the classification of Multiple Endocrine Neoplasia?
Type 1: Pituitary tumors (prolactin); Primary hyperparathyroidism (hypercalcemia); Pancreatic tumors (gastrinomas)
Type 2A: Medullary thyroid cancer (calcitonin); Pheochromocytoma; Parathyroid hyperplasia
Type 2B: Medullary thyroid cancer; Pheochromocytoma; oral and intestinal mucosal neuromas/marfanoid habitus; inherited mutation in RET proto-oncogene
70
What are the different types of mosaicism?
Somatic mosaicism affects the cells forming the body, causing disease manifestations to develop in affect individuals
Germline mosaicism: affects the cells that give rise to gametes, allowing affected genes to pass to offspring; chance of child beign affected depends on proportion of gametes that carry mutation; when mutation is limited to germline, the affected parent does not develop clinical manifestations
71
What are nontypeable strains of Haemophilus influenzae?
Nontypeable strains of H flu are part of the normal URT flora and are a common cause of acute otitis media, sinusitis, and bronchitis.
Because nontypeable strains do not form a polysaccharide capsule, immunity is not conferred by vaccination with the H flu type b vaccine.
Vaccine stimulates a helper T cell response to help activate B cell antibody formation. A cell-mediated cytotoxic T cell response is not induced.
72
What is zolpidem?
A short-acting hypnotic agent structurally unrelated to benzodiazepines.
MOA: binds to GABAa receptor and enhances inhibitory action of GABA on CNS
Indication: short-term treatment of insomnia
Properties: less potential for tolerance and addiction; no anticonvulsant properties; no muscle relaxing effects and not used for anesthesia
73
Where are Beta1 adrenergic receptors found?
Beta1 adrenergic receptors are found in **cardiac tissue** and on **renal juxtaglomerular cells**, but not in vascular smooth muscle.
Selective blockage of the Beta1 receptor (e.g, with atenolol) leads to decreased cAMP levels in cardiac and renal tissue w/o significantly affecting cAMP levels in vascular smooth muscle.
74
What is aspiration pneumonia?
Predisposing condition: altered consciousness impairing cough reflex/glottic closure; **dysphagia** due to neurologic deficits; upper GI disoreders; mechanical compromise of aspiration defenses; protracted vomiting; large volume feedings in recumbent position
Pathogenesis: anaerobic bacteria from oral cavity
Presentation: posterior regions of upper lobes and superior region of lower lobes have infiltrate (while supine); basilar (lower) segments while upright
75
What are signs of low serum ca? high serum calcium?
**Low**: tetany, seizures, QT prolongation, twitching (Chvostek sign), spasm (Trousseu sign);
**High**: stones (renal), bones (pain), groans (abdominal pain), thrones (increase urinary frequency), psychiatric overtones (anxiety, altered mental status)
76
What muscles are responsible for motion at the hip?
Flexion: **iliopsoas\*** (psoas major, minor, and iliacus), rectus femoris, tensor fascia lata
Extension: biceps femoris-long head, gluteus maximus, semimembranosus, semitendinosus
Abduction: gluteus medius, gluteus minimus
Adduction: adductor brevis, longus, magnus
77
What is halothane hepatitis?
Acute hepatitis due to exposure to halogenated inhaled anesthetics during surgery.
Halothanes = halothan, enflurane, isoflurane, sevoflurane, desflurane
Pathogenesis: Metabolism by cyp450 converts halothans to reactive intermediates that directly injure the liver or lead to immune-mediated hepatocellular damage.
Presentation: 2-3 weeks after medicationi exposure; fever, nausea, jaundice (scleral icterus), tender hepatomegaly, elevated AST, ALT, and bilirubin
Gross: centrilobular hepatic necrosis
Tx: supportive; no specific beneficial therapies
78
What is hyperestrinism?
Pathogenesis: due to increased adrenal productioni of androstenedione with aromatization to estrone and eventual conversion to estradiol; Impaired estrogen metabolism by liver;
estradiol induces sex hormone binding globulin production (primarily in liver, but also in uterus and testes), which results in increased T binding and decreased free T/E ratio; leads to gynecomastia, testicular atrophy, decreased body hair, and spider angiomata
79
What is hemoglobin c disease?
Pathogenesis: caused by missense mutation that results in glutamate residue being substituted by **lysine** in the beta globin chain.
Results in overall decrease in negative charge for hemoglobin molecule.
Presentation: typically asymptomatic and often have mild hemolytic anemia and splenomegaly
Speed of hemoglobin movement during gel electrophoresis: HbA\>HbS\>HbC.
80
What is RNA interference?
A mechanism by which short (20-30 base pair) non-coding RNA sequences induce postranscriptional gene silencing by base-pairing with complementary sequences w/in target mRNA molecules; includes microRNA and small interfering RNA
Can cleave mRNA or repress translation
81
What are the different types of ribosomes?
Free ribosomes: remain floating in cytosol throughout protein synthesis; translate proteins found in cytosol, nucleosol, peroxisome matrix, and nuclear-encoded mitochondrial proteins
Attached ribosomes: bind to RER after protein translation begins; synthesize most secretory proteins, the integral membrane proteins of nucleus and cell membrane, and proteins within the ER, golgi network and lysosomes
Smooth ER lacks surface ribosomes: functions in lipid synthesis, carbohydrate metabolism, and detoxification of harmful substances
82
What is hemosiderin?
Iron binds to apoferritin to form ferritin micelles, these accumulate in macrophages of the reticuloendothial system creating hemosiderin. Appears as **brown or yellowish-brown pigment**.
Hemosiderin accumulation is cardinal histologic finding in iron overload (hemosiderosois), a common and serious complication of chronic hemolytic anemia and frequent blood transfusions.
83
What is systemic lupus erythematosus?
Pathogenesis: **autoantibody production** due to loss of self-tolerance; autoantibodies against nuclear components (anti-nuclear antibodies)
Presentation: SOAP BRAIN MD
Serositis (pleuritis, pericarditis), Oral ulcers, Arthritis (symmetric, migratory), Photosensitivity, Blood (all are low - anemia, leukopenia, thrombocytopenia, complement; **type II** **hypersensitivity**); Renal (Lupus nephritis = nephrotic/nephritic syndrome - **type III hypersensitivity**); Antibodies, Immunologic (anti dsDNA), Neurologic (psychosis, seizures), Malar rash, Discoid rash
Labs: anemia, leukopenia, thrombocytopenia;
Positive ANA, anti-dsDNA, anti-smith (specific); **low complement levels, increased immune complexes**
84
What is Marfan syndrome?
Pathogenesis: inherited defect in **fibrillin-1-gene;** fibrilin 1 is major component of microfibrils that form a sheath around elastin fibers, acts as a scaffold for elastin; microfibrils are abundant in blood vessels (aortic media), periosteum and suspensory ligaments/zonular fibers of the lens
Presenation:
skeletal - arachnodactyly
ocular - ectopia lentis
cardiovascular - aortic dilation, AR, dissection, MVP
pulm - spontaneous pneumothorax from apical blebs
skin - recurrent or incisional hernia, skin striae
85
What is lead poisoning?
Pathogenesis: lead binds to sulfydryl groups on proteins, replaces Ca in Ca-dependent cellular functions, and directly inhibits enzymes in heme synthesis (ferrochelatase and ALA dehydratase); exposure risk increased in old homes w/ chipped paint
Presentation:
Neurologic: **language** regression; loss of milestones/cognitive impairment, **behavioral** **problems** (tantrums); encephalopathy
GI: constipation, abdominal pain, decreased vitamind D metabolism; lead lines on gingiva; lead lines on metaphyses of long bones
Renal: interstitial nephritis
Hematologic: anemia
Wrist and foot drop
Risk factors: sibling with prior elevated lead levels, living in older homes with recent renovation
Histology: basophilic stippling due to inhibition of rRNA degradation
Dx: measuring blood lead level; increased urine delta-aminolevulinic acid
Tx: dimercaprol and EDTA; succimer for chelation in children
86
What is a lung hamartoma?
The most common **benign** lung tumor (pulmonary chondroma); lung is the most common location for hamartoma
Histology: islands of mature **hyaline cartilage**, fat, smooth muscles and clefts lined by respiratory epithelium; fibrous and adipose tissue
CXR: asymptomatic; appear as peripherally located well-defined coin lesion with "popcorn calcifications"; patients 50-60yo
Hamartoma: excessive growth of tissue type native to organ
87
What is the primary route for copper excretion?
Senescent ceruloplasmin and unabsorbed copper are **secreted into bile and excreted in stool**.
88
What is the minimum alveolar concentration (MAC)?
It is a measure of **potency** of an inhaled anesthetic.
It is the concentration of the anesthetic in the alveoli tha renders 50% of pts **unresponsive to painful stimuli** (ED50).
Potency is **inversely proportional** to mac: the lower the MAC, the more potent the anesthetic.
89
What is the blood/gass partition coefficient?
It corresponds to the **solubility** of anesthetic in the blood.
Anesthetics with a **high blood/gas partition** coefficient are absorbed to a **greater** extent by the blood and have a **slower onset of action**.
90
What is thoracic outlet syndrome?
It is due to compression of the lower trunk of the brachial plexus in the scalene triangle, the space bordered by the anterior and middle scalene muscles and the first rib.; can be due to an **anomalous cervical rib**
Sx: upper extremity numbness, tingling, and weakness.
Compression of subclavian vein: upper extremity swelling
Compression of subclavian artery: exertional arm pain
91
What are the roles of DNA pol I and III in bacteria?
DNA pol I: removes **RNA primers** (via 5' to 3' exonuclease activity) and replaces them with DNA (via 5' to 3' polymerase activity).
DNA pol I is the only bacterial DNA pol that possesses **5 to 3 exonuclease activity**.
DNA pol III: has 5 to 3 polymerase and **3 to 5 exonuclease (proofreading: removes mismatched nucleotides**) activity; however, it cannot remove RNA primers b/c it lacks 5 to 3 exonuclease activity.
92
What are two peroxisomal disorders?
Peroxisomes: oxidize very long chain and branched chain fatty acids (e.g., phytanic acid)
**Zellweger syndrome**: defective peroxisomal biogenesis
Presentation: craniofacial abnormalities, hepatomegaly, neurologic defects
**X-linked adrenoleukodystrophy:** defective transport of VLCFAs into peroxisomes
Presentation: neurologic deterioration and adrenal insufficiency due to accumulation in CNS and adrenal glands
93
What is somatic symptom disorder?
Patient preoccupation with unexplained medical symptoms and excessive health care use.
Tx: schedule regular visits taht focus on goal of functional improvement; avoid unnecessary diagnostic testing and specialist referrals
94
What is diphenoxylate?
An opioid antidiarrheal drug that binds mu opiate receptors in the gut to **slow motility**.
Overuse can lead to euphoria and physical dependence.
To discourage abuse, diphenoxylate is combined with atropine which induces adverse effects if taken in high doses.
95
What is haptoglobin?
A serum protein that binds to free hemoglobin and promotes its uptake by the reticuloendothelial system.
Haptoglobin levels decrease when significant quantities of hemoglobin are released into circulation, as occurs with intravascular hemolysis.
96
How does a lesion in the optic tract affect the afferent pupillary light reflex?
A lesion in the optic tract can produce contralateral homonymous hemianopia and a relative afferent pupillary defect (Marcus Gunn pupil) in the pupil **contralateral to the tract lesion**.
Nasal portion of the retina contributs more input to the pretectal nucleus.
97
What is gastroesophageal reflux disease?
Pathogenesis: gastroesophageal junction incompetence; can be associated with extraesophageal symptoms (e.g., nocturnal cought) in absence of heartburn; acidic gastric contents irrate esophageal mucosa
Histology: basal zone hyperplasia, elongation of lamina propria papillae, scattered eosinophils and neutrophils
98
How does ether impact enveloped viruses?
Ether and other organic solvents can **inactivate enveloped viruses** by dissolving the lipid bilayer that makes up the outer viral envelope. Loss of infectivity after ether exposure is a characteristic feature of enveloped viruses.
Non-enveloped viruses are resistant to the action of ether.
99
What are the different types of transplant rejection?
**Hyperacute:** occurs w/in minutes of transplantation; preformed antibodies against ABO or HLA; widespread thrombosis of the graft vessels --\>ischemia/necrosis
**Acute:** 1-2w later; cell-mediated **(CD8s)**; antibodies develop after transplant; cuases vascular damage with dense interstitial lymphocytic infiltrate
**Chronic**: months to years later: CD4s respond to recipient APCs presenting donor peptides, including allogenic MHC; proliferation of vascular smooth msucle, parenchymal atrophy, interstitial fibrosis; dominated by atherosclerosis
Lungs: inflammation of **small bronchioles** (**bronchiolitis obliterans**); sx - dyspnea, wheezing, nonproductive cough
Graft versus host disease
100
What is rheumatoid arthritis?
Presentation: pain, swelling and **morning stiffness** in multiple joints; **small joints** (PIP, MCP, MTP), spares DIP; wrists, elbows, knees; **_cervical spine_** involvement, which causes jt destruction w/ vertebral malalignment (**subluxation**) affecting atlantoaxial joint; joint destruction; pts can develop **interstial** **lung** **diseases** (from pulmonary manifestations of disease itself and drugs - methotrexate, cyclophosphamide, and sulfasalazine)
Chronic sx of cervical subluxation: neck pain, stiffness, sensory loss, muscle weakness; extension of neck during endotracheal intubation can worsen subluxation and cause compression of spine/vertebral arteries; leads to **spinal shock** (flaccid paralysis, decreased/absent reflexes)
Labs/imaging: positive rheumatoid factor and **anti-CCP antibodies**; c-reactive protein and ESR correlate with disease activity
X-ray: soft tissue sweling, joint space narrowing, bony erosions
Tx: NSAIDs or systemic steroids provide temporary relief; **DMARDS** are recommended to avoid progressive joint destruction
101
What are the different eating disorders?
Anorexia nervosa: **significantly low weight**; intense fear of weight gain; distorted views of body weight and shape
Bulima nervosa: Recurrent episodes of binge eating; **Compensatory behavior**: vomiting, exercise; to prevent weight gain; Excessive worry about body shape and weight; Maintains **normal body weight**; must occur at least once a week for 3mo
Binge-eating disorder: recurrent binge eating with lack of control; **no compensatory behaviors**; must occur at least once a week for 3mo
102
What is body dysmorphic disorder?
Characterized by **intense preoccupation with perceived defect** in physical appearance leading to significant functional impairment.
It is not diagnosed when weight gain is the preoccupation of an individual who meets criteria for an eating disorder.
103
What is Hartnup disease?
Pathogenesis: autosomal recessive; caused by inactivating mutations affecting neutral amino acid transporter in SI and proximal tubule of the kidney; **low tryptophan**, which is essential amino acid and precursor for **niacin, serotonin, and melatonin**
Presentation: **pellagra-like skin eruptions**; **cerebellar ataxia**
Dx: excessive amounts of neutral amino acids in urine
Tx: high protein diet with daily niacin or nicotinamid supplementation
104
Why does disseminated intravascular coagulation occur in pregnancy?
Pathogenesis: mediated by tissue factor (thromboplastin), found in high concentration in placental trophoblast; tissue factor is released from sites of placental injury, initiating the coagulation cascade
Presenation: vaginal bleeding, uterine tenderness, retroplacental hematoma, fetal demise are consistent with abruption
Labs: clotting factors and platelets are rapidly consumed, resulting in profound bleeding from incision sites, IV line sites, and mucosal surfaces (e.g., gums, vagina)
105
What is Stewart-Treves syndrome?
Cutaneous angiosarcoma
Risk factor: radical mastectomy w/ axillary lymph node dissection is a classic predisposing procedure for **chronic lymphedema**; chronic lymphedema predisposes to development of **angiosarcoma** (Stewart Treves syndrome)
Histology: infiltration of dermis w/ slit-like abnormal vascular spaces
Prognosis: poor; tumor is usually widespread by time of dx
106
What are the mood stabilizers for bipolar disorder?
Carbamazepine and Valproate: **manic features**; valproate is also an anticonvulsant (treats generalized tonic-clonic, myoclonic seizures)
Lithium: **manic and depressive** features
Lamotrigine: **depressive** features
107
What is malignant hyperthermia?
Pathogenesis: due to hypersensitivity of skeletal muscles to **inhalation anesthetics** (especially halothane) and muscle relaxant succinylcholine; autosomal dominant; defect of ryanodine receptor - releases large amounts of Ca after exposure to anesthetic; excessive consumption of ATP by SERCA generates heat
Presentation: **fever, muscle rigidity** soon after surgery under general anesthesia; tachycardia, HTN, hyperkalemia, myoglobinemia
Tx: dantrolene; muscle relaxant that acts on ryanodine recptor and prevents further release of Ca into cytoplasm of muscle fibers
108
What is malrotation?
Pathogenesis: incomplete counterclockwise rotation
Presenation: **Ladd's (fibrous) bands** connect retroperitoneum in the RLQ to the right colon/cecum, causing intestinal **obstruction and compression of duodenum**; obstruction manifests as **bilious emesis** during first days of life; b/c mesenteric base is abnormally narrowed, the mesentery is vulnerable to twisting around the superior mesenteric artery **(volvulus)** --\>compromises intestinal perfusion and leads to necrosis
109
What is spinal muscular atrophy?
SMA type 1 = Werdnig Hoffmann disease
Pathogenesis: mutations in **survival motor neuron (SMN1) gene**, which encodes a protein involved in assembly of small nuclear ribonucleoproteins **(snRNPs)** in the lower motor neurons; defective snRNP assembly results in impaired spliceosome function and degeneration of anterior horn cells in the spinal cord
Spliceosomes remove intron from pre-mRNA during processing w/in the nucleus
Presentation: "floppy baby"; **flaccid paralysis; fasciculations; generalized hypotonia, decreased deep tendon reflexes;** death occurs w/in a few years after birth
110
What is the serratus anterior?
Origin: surface of first 8 ribs
Insertion: medial border of scapula
Innervation: long thoracic nerve
Function: to stabilize and rotate the scapula upward; allows abduction of arm past horizontal
**Dissection of axillary lymph nodes** can injure the **long thoracic nerve**; results in weakness of serratus anterior w/ winging of the scapula and impaired abduction of should past horizontal
111
How does radiation therapy treat cancer?
Therapeutic/palliative ionizing radiation (e.g., gamma rays, x rays) work by:
DNA ds breakage: breakage of both strands is generally required; single strand breaks are easily repaired by polymerases
Free radical formation: reactive O2 species are formed by ionization of water; O2 free radicals are able to causes cellular and DNA damage
112
What stimulates each section of the adrenal gland?
The **zona glomerulosa** is primarily regulated by **angiotensin II**.
ACTH is the major trophic hormone of the **zona fasciculata and reticularis**.
Prolonged ACTH stimulation causes **hyperplasia** of the zona fasciculata and reticularis resulting in excessive cortisol production (Cushing syndrome).
113
What is hepatocellular cancer?
A **liver mass assoc. w/ an increased alpha fetoprotein** is a typical presentation of hepatocellular carcinoma.
Pathogenesis: the i**ntegration of viral DNA** into the cellular genome of the host is considered a trigger of neoplastic changes. HBV gene products suppress p53 in host cells.
Other risk factors: HCV, alcoholic cirrhosis, aflatoxins, and hemochromatosis
114
What is the inciting event for acute appendicitis?
Presentation: inflamed, hyperemic, edematous; RLQ abdominal pain
Pathogenesis: **obstruction of the appendicular lumen** by **fecaliths**; others - hyperplastic lymphoid follicles, foreign bodies, nematodes, carcinoids
If the appendix cannot be identified by palpitation during an appendectomy, it can be located by following the **teniae coli** to their origin at the cecal base/root of the **vermiform appendix**.
115
What is abetalipoproteinemia?
Pathogenesis: Autosomal recessive; loss of function mutation in the MTP gene; inability to synthesize apolipoprotein B, an important component of chylomicrons (apoB48) and very low density lipoprotein (apoB 100); lipids absorbed by SI cannot be transported into blood and accumulate in intestinal epithelium, resulting in enterocytes with clear or foamy cytoplasm
Presentation: abdominal distention, foul-smelling stool
Labs: low plasma TG and cholesterol levels; chylomicrons, VLDLs, and apoB are absent from blood; low vit ADEK and essential fatty acids; acanthocytes (RBCs with abnormal membrans and thorny projections; ataxia, retinitis pigmentosa)
116
What are interferons?
**Type I interferions** (**alpha and beta)** are made by most human cells in response to viral infections. They help suppress viral replication by h**alting protein synthesis and promoting apoptosis of infected cells**, limiting ability of viruses to spread. Only active in presence of **dsRNA (infected cells**).
**Type II (gamma)** produced by T cells and NK cells; promotes Th1 differentiation, increases expression of MHCII on APCs, improves intracellular killing ability of macrophages
117
What are selective COX2 inhibitors?
Celecoxib;
They have potent anti-inflammatory effects w/o the side effects of bleeding and GI ulceration associated with non-selective COX inhibitors.
Selective COX2 inhibitors do not impair platelet function because platelets predominantly express COX2.
NSAIDs reversibly inhibit COX1 and COX2.
118
What is Treacher-Collins Syndrome?
Genetic disorder resulting in abnormal development of the **1st and 2nd pharyngeal arches**.
Presentation: airway compromise and feeding difficulties (mandibular, maxillary, zygomatic bone hypoplasia); profound hearing loss (absent or abnormal ossicles)
119
What is hepatis B infection?
Most common cause of hepatic injury in US. Transmission: sex or IV drug use
Pathogenesis: causes hepatocellular cytoplasm to fill with hep B surface antigen.
Histology: accumulation of HBsAg results in finely granular, diffusely homogeneous, pale eosinophilic cytoplasm (**"ground glass" hepatocytes)**
120
What is norovirus?
Most common cause of viral gastroenteritis. Transmission: fecal-oral spread Epi: ssRNA
Presentation: diarrhea (watery w/o blood or mucus), vomiting, fever, malaise, HA; acute onset; resolves in 2-3d
**Outbreaks** (e.g., schools, cruise ships, nursing homes) are common.
121
What is liquefactive necrosis?
Liquefactive necrosis is characterized by complete digestion and removal of necrotic tissue with formation of cystic cavity.
**Release of lysosomal enzymes** from ischemic neurons results in degradation of tissue in the ischemic region.
Abscess formation due to bacterial or fungal infection is another ex of this type of necrosis.
122
What are the proto-oncogenes?
**1-hit GAIN of function mutation;**
ABL (nonreceptor tyrosine kinase) - chronic myelogenous leukemia
BRAF (Ras signal transduction) - hairy cell leukemia; melanoma
ERBB1 (EGFR; receptor tyrosine kinase) - lung adenocarcinoma
ERBB2 (Her2; receptor tyrosine kinase) - breast cancer
MYC (transcription factor) - Burkitt lymphoma
RAS (GTP binding protein) - cholangiocarcinoma, pancreatic adenocarcinoma
123
What are the tumor suppressor genes?
**2-hit LOSS of function;**
APC/Beta catenin (Wnt signaling pathway) - colon, gastric and pancreatic cancer; familial adenomatous polyposis
BRCA1/2 (dsDNA break repair genes) - breast and ovarian cancer
RB (G1/S transition inhibitor) - retinoblastoma; osteosarcoma
TP53 (genomic stability) - most cancers; Li-Fraumeni syndrome
VHL (ubiquitin ligase component) - renal cell carcinoma, von hippel lindau syndrome
WT1 (urogenital differentiation) - Wilms Tumor
124
What are the watershed areas of the GI system?
The **splenic flexure** (border b/n SMA and IMA supply) and **rectosigmoid junction** (border b/n sigmoid artery and super rectal artery) lie between regions of perfusion of major arteries.
These watershed areas are susceptible to ischemic damage during hypotensive states, especially in patiens with underlying arterial insufficiency.
125
What is the arteriovenous concentration?
The arteriovenous concentration gradient reflects the overall tissue solubility of an anesthetic.
**High tissue solubility**: **large arteriovenous concentration gradients**, **slower onsets of action.**
126
What is polyarteritis nodosa?
Pathogenesis: idiopathic; associated with **Hep B** infection in up to 30% of cases
Presentation: **segmental, transmural inflammation** of arterial wall with **fibrinoid necrosis**; affects small to medium arteries, can occur in any organ **EXCEPT the lung**
Renal: glomerulonephritis, HTN
CNS: peripheral neuropathy, mononeuritis multiplex
GI: mesenteric ischemia/bowel infarction, bleeding
MSK: myositis, arthritis
127
Where are the 3 parts of the duodenum in relation to arteries?
1st part: not retroperitoneal; horizontally oriented over 1st lumbar vertebra
2nd part: courses inferiorly from level of L1 to L3; in close relation to head of pancreas and contains ampulla of Vater
3rd part: courses horizontally over L3, the abdominal aorta, and the inferior vena cava; in close association with uncinate process of pancreas and posterior to the **superior mesenteric artery and vein**
4th part: courses superiorly and to left of L2 and L3; becomes jejunum past the **ligament of Treitz**
128
What is placental aromatase deficiency?
Autosomal recessive; manifests early in embryonal life with high androgen and low estrogen levels in female uterus;
Maternal virilization (e.g., hirsutism) commonly occurs during pregnancy due to transfer of excess androgens into maternal circulation
Affected newborn girls: normal internal genitalia, ambiguous or male-type external genitalia; at puberty: impaired ovarian estrogen synthesis causes primary amenorrhea, osteoporosis, and tall stature (low estrogen delays fusion of epiphyses)
Men: tall stature and osteoporosis, no gential abnormalities
Aromatise: converts androgens to estrogens in ovaries, testes, placenta, and other peripheral tissues.
129
What is cerebellar degeneration?
Pathogenesis: long-term, heavy alcohol use leads to cerebellar vermis atrophy
Presentation: gait ataxia, truncal instability, rhythmic, postural tremor of fingers and hands; diplopia
130
What is metoclopramide?
Used to treat vomiting or gastroparesis
It can exacerbate or cause de novo parkinsonian symptoms and trigger extrapyramidal reactions due to antagonistic effect on dopamine receptors.
Contraindicated in patients with parkinson's disease.
131
What is the difference between Marfan's and homocystinuria?
Overlapping features: pectus deformity, tall stature (increased arm:height, decreased upper:lower segment); arachnodactyly; joint hyperlaxity, skin hyperelasticity, scoliosis
Marfans: AD, normal intellect, aortic root dilation, UPWARD lens disloction
Homocystinuria: AR; i**ntellectual disability, thrombosis** (hypercoagulability), **DOWNWARD lens dislocation** (ectopia lentis), megaloblastic anemia, fair complexion; due to cystathionine beta synthase gene mutation
132
What is a pinealoma?
Tumors are accompanied by HA and n/v due to obstruction of cerebral aqueduct and resulting hydrocephalus. May also damage dorsal midbrain in the superior colliculus due to mass effect, which leads to Parinaud syndrome
Presentation: **upward gaze palsy**, absent pupillary light reflex, and impaired convergence
Lateral gaze palsy: results from pontine lesionis affecting CN6; frontal lobe infarct can also cause lateral gaze palsy due to damage to frontal eye field
133
What is tardive dyskinesia?
Pathogenesis: medication-induced movement disorder; due to prolonged exposure to dopamine-blocking agents causing the upregulation and supersensitivity of dopamine receptors
Presentation: abnormal involuntary movements of the mouth, tongue, trunk, and extremities (lip puckering, smacking, facial grimacing, blinking, choreiform movements of extremities); may be irreversible
134
What is contact inhibition?
When normal cells are cultured in a petri dish, they reproduce until medium is covered with single layer of cell that just touch once another; mitosis halts, mediated by cadherins and catenins = **"contact inhibition"**
Malignant cells will cover medium with single layer of cell and then continue to divide, piling up into pounds; do not show contact inhibition
135
How do dsDNA viruses infect cells?
All dsDNA viruses replicate in the nucleus (except poxvirus, which replicates in cytoplasm);
Host cell **DNA dependent DNA polymerase** facilitates replication of viral genome w/in host cell nucleus.
Transcription of viral DNA into mRNA is facilitated by DNA dependent RNA pol. Among processed proteins produced is a viral DNA dependent DNA polymerase which facilitates viral genome replication.
136
What is orlistat?
An **intestinal lipase inhibitor** that reduces absorption of dietary fat.
Uses: first line medication for obesity; produces modest weight loss
SEs: GI (diarrhea, fecal incontinence, flatulence, oily spotting)
137
What is xerosis?
Itchy rash and dry, cracked skin; common in older pts during winter
Patients have defects in stratum corneum permeability barrier --\> excessive transepidermal water loss, penetration by chemicals and irritants
Tx: bathing with lukewarm water, **moisturizing** **immediately** after bathing; emollient moisturizers
138
What is follicular lymphoma?
An indolent non-Hodgkin lymphoma
Pathogenesis: **translocation of bcl2 oncogene** from ch18 to ch14 [t(14;18)]; bcl2 protein product that inhibits tumor cell apoptosis is **overexpressed** as result (keeps cells alive)
Presentation: waxing, waning lymphadenopathy; involved lymph nodes contain tightly packed lymphoid follicles with small lymphocytes w/ cleaved nuclei and large non-cleaved lymphocytes
139
What is primary ovarian failure?
Amenorrhea in women age \<40yo.
Pathogenesis: result of follicular depletion through accelerated atresia, an apoptotic process; can occur due to chemotherapy; or inadequate development of ovarian follicles
Labs: elevated gonadotropins (FSH) and low estrogen
140
What is the result of damage to the peroneal nerve?
Common causes of injury include nerve compression at the fibular neck (e.g., due to tight fitting casts or boots) and trauma to the lateral leg just below the knee.
Presentation: **"foot drop" (inability to walk on the heels**) w/ sensory loss over the lateral leg and dorsolateral foot.
141
How does a psoas abscess form?
The psoas muscle originates at the T12-L4 vertebrae, passes below the inguinal ligament and over the wing of the ilium, and attaches to lesser trochanter of the femur.
Psoas does NOT enter true pelvis. On the R, psoas muscle lies in close proximity to the appendix, right ureter/renal pelvis, pancreatic head/uncinate process, and spine. Spread of infection of any of these structures can cause a psoas abscess to form.
Spread of pus along the psoas musle leads to abscess formation in the groin and pain referred to that region.
142
What is Wilson's Disease?
Pathogenesis: autosomal recessive
Presentation: copper accumulation in liver, brain, kidney, and eye (Descemet's membrane of cornea; brownish or gray-green rings of granular copper); hepatitis, splenomegaly, hemolytic anemia
Neuro: dystonia, tremor, dysarthria, and dysphagia
Dx: rings are identifiable on slit lamp examination
143
What is the effect of flumazenil on benzodiazepines and barbituates?
Benzos: effect is **reduced** by flumazenil, which competitively inhibits benzo binding to the GABA receptor
Barbs: flumazenil has **no effect** on barbituates, which bind to a different site on the GABA receptor
144
What is a leucine zipper?
Basic-region leucine zippers are a class of eukaryotic transcription factors composed of **2 alpha-helical proteins** that combine to form a dimer; transcription factor
Each dimer has a DNA binding region composed of basic amino acids and a leucine zipper dimerization domain that contains repeated leucine residues at **every seventh position**
145
What is glucokinase?
Glucose sensor expressed in **pancreatic beta cells**; catalyzes phosphorylation of glucose to glucose-6-phosphate; also expressed in the liver and involved in glycogen synthesis; has **low affinity for glucose** and thus requires a higher concentration of glucose for activation; mutations that impair expression of glucokinase raise the glucose threshold for insulin release, leading to maturity-onset diabetes of the young, which is characterized by mild, non-progressive hyperglycemia that often worsens w/ pregnancy induced insulin resistance
**Hexokinase:** expressed in most cells, **EXCEPT liver and pancreatic beta cells**; has high affinity for glucose, allowing its utlization at low glucose levels for cellular homeostasis; deficiency characterized by hemolytic anemia
146
What is von gierke disease?
Type 1 glycogen storage disease; caused by deficiency in **glucose 6-phosphatase**
Presentation: severe fasting hypoglycemia that does not improve with fructose of galactose administration, lactic acidosis, hyperlipidemia, hyperuricema; hepatomegalyc, steatosis
Tx: frequent oral glucose loading (e.g., uncooked cornstarch); avoid foods containing fructose and galactose as these cannot be converted to free glucose
147
What is pompe disease?
Type II glycogen storage disease; deficiency in **acid alpha-glucosidase** (lysosomal enzyme)
Presentation: hypotonia, normal glucose levels; **severe cardiomegaly**, glycogen accumulation in **lysosomes**; only glycogen storage disease that presents with cardiomegaly in infancy
Histology: lysosomes accumulate glycogen and are **PAS positive**
148
What is cori disease?
Type III glycogen storage disease; deficiency in debranching enzymes (alpha 1,4 transferase and alpha 1,6-glucosidase); inability to degrade alpha 1,6 glycosidic branch points
Presentation: hepatomegaly; ketotic hypoglycemia (ketoacidosis), hypotonia and weakness, abnormal glycgoen with very short outer chains (limit dextrins)
149
What is mcardle disease?
Type 4 glycogen storage disease; deficiency in **muscle glycogen phosphorlyase**
Presentation: **weakness and fatigue w/ exercise**; **no rise** in blood lactate levels after exercise; myoglobinuria (red urine); symptoms classically improve w/ brief periods of rest (second wind phenomena)
Hypoglycemia is NOT a feature of McArdle disease, as liver glycogenolysis remains intact due to presence of separate hepatic isozyme.
150
What is Tarui disease?
**Deficiency in phosphofructokinase** (catalyzes conversion of fructose 6 phosphate to fructose 1,6 bisphosphate)
Presentation: exercise-induced muscle weakness, cramping, rhabdomyolysis
151
What are the typical lab findings in disseminated intravascular coagulation?
Feared complication of sepsis.
Presentation: bleeding and/or thrombosis; intravascular coagulationi can cause microangiopathic hemolytic anemia (MAHA);
Labs: l**ow serum fibrinogen, platelets**; **HIGH/elevated - PT, PTT, fibrin degradation products;** **schistocytes** in setting of MAHA
152
What is acute lumbosacral radiculopathy?
Pathogenesis: caused by compression of the L5 or S1 nerve roots due to vertebral disc herniation, w/ disruption of the annulus fibrosus and subsequent prolapse of the nucleus pulposus
Presentation: back pain radiating to the foot, diminished lower extremity reflexes and a positve straight leg raise test
153
What is osteomyelitis?
Pathogenesis: in children, results from hematogenous seeding during an episode of bacteremia; s. aureus is common cause of acute hematogenous osteomyelitis in children, **salmonella** common cause of osteomyeltis in pts with **sickle cell disease** due to splenic dysfunction and increased bacterial translocation from occluded intestinal segments
Salmonella is non-lactose fermenting, oxidase negative, gram neg rod, H2S positive (black), motile, encapsulated (protected from opsonization and phagocytosis)
Risk factor: sickle cell disease - slow blood flow through small metaphyseal capillary loops allows bacteria to seed the bone
Presentation: fever and bone pain; ROM and weight bearing are impaired
Presentation of hematogenous osteomyelitis: children/boys; affects the _**metaphysis** **of long bones**_ due to slower blood flow and capillary fenestrae in the region; w/o proper tx infection can progress to chronic suppurative osteomyelitis; tx: antibiotics and debridement of necrotic bone
154
What are the different types of acute intracerebral hemorrhage?
Nontraumatic intracerebral hemorrhage (ICH) in the absence of aneurysms is most commonly associated with HTN. Most commonly affected sites thalamus and putamen.
Thalamic ICH: contralateral sensory loss, aphasia, temporary homonymous hemianopia; unilateral CN6 nerve palsy, pupil asymmetry and non-reactivity, **downward gaze**
Putamen ICH: contralateral motor deficit, persistent homonymous hemianopia, aphasia; **dilated pupils**
Pontine: **pinpoint pupils**, l**oss of horizontal gaze**, **quadriperesis**, decerebrate posturing, rapily evolving coma (reticular activating system disruption) that culminates in **death w/in hours**
Lobar ICH: contralateral hemiparesis or sensory loss, contralateral conjugate gaze paresis, contralateral homonymous hemianopia, aphasia, apraxia, memory deficits
Cerebral ICH: **ipsilateral** facial weakness or sensory loss, ataxia, gaze paresis, miosis, decreased consciousness; strength in extremities is preserved, limb posturing not observed
155
What are the side effects of tacrolimus and cyclosporine?
Tacrolimus and cyclosporine are common immunosuppressive agents used to prevent rejection of transplanted solid organs, and in inflammatory disorders (e.g., severe psoriasis).
Calcineurin inhibitor **nephrotoxicity** is dose-related and manifests as a rise in serum BUN and creatinine levels as well as increased blood pressure.
156
What are the hallmarks of ischemic injury?
Tissue ischemia increases extracellular K+ concentration via reduced functionality of membrane NaKATPase and subsequent K leakage from affected cells.
Ischemia reduces extracellular Na, Ca and HCO3-.
**Cytoplasmic Ca2+** accumulation is a hallmark of ischemic injury.
157
Describe heparin vs. warfarin solubility.
**Water soluble** materials (conjugated bilirubin) do not readily cross the placenta; **heparin**
while **lipophilic** materials (unconjugated bilirubin) easily cross the placenta.
**Warfarin is lipophilic**.
158
What is acitretin?
A synthetic retinoid used systemically to treat psoriasis. All systemic retinoids are strongly teratogenic.
Promotes cellular differentiation and has immunomodulatory and anti-tumor effects.
159
What are the charges of the amino acids at physiologic pH?
Nonpolar (uncharged=**hydrophobic**): **alanine, phenylalanine, glycine, isoleucine, leucine, methionine, proline, tryptophan**; in the transmembrane domain of G protein coupled receptors
**Acidic**: **aspartate**, **glutamate**; carry **negative** charge = **hydrophilic**
**Basic**: histidine, lysine, arginine; carry **positive** charge = **hydrophilic**
160
Where do RNA viruses replicate?
All R**NA viruses** [except for influenza and HIV] replicate in the **cytoplasm.**
Inflluenza replicates in the **nucleus**.
161
What are atypical nevi?
The dysplastic nevus syndrome manifests with numerous dysplastic nevi in young person with family hx of melanoma in more than 3 first degree relatives.
Pathogenesis: mutations in the **CDKN2A** gene on chromosome **9p21**; increased chance of melanoma
Histology: dermoepidermal junction aggregates of large cells that fuse w/ adjacent nests; irregular nuclear contours, hyperchromasia, are round or spindle shaped
162
What is liver angiosarcoma?
Rare, malignant **vascular** **endothelial** cell neoplasm; Carcinogen-related neoplasm composed of cells taht express **CD31** (an enothelial cell marker), which is **PECAM1**.
PECAM1 is expresses on the surface of endothelial cells and function in leuckocyte migrationi through the endothelium. Patient's tumor cells rose from vascular endothelial cells.
Risk factors: exposure to **arsenic** (pesticides), **thorotrast** (radioactive contrast medium), **polyvinyl** (plastic used in industry)
