STEP 1

What is derived from neural crest cells?

"MAGIC COPS" Melanocytes, Aorticopulmonary septum, Ganglia, Iris (stroma), Chromaffin cells, Cranial nn, Ossicles/Odontocytes, Parafollicular cells (of thyroid; secrete calcitonin), Sclera

What are the drugs that act on microtubules?

- "Microtubules Get Constructed Very Poorly" - Mebendazole (antihelminthic) - Griseofulvin (antifungal) - Colchicine (antigout) - Vincristine/Vinblastine (anticancer) - Paclitaxel (anticancer)

Damage to the corpus callosum

- "split brain" syndrome: pt may appear normal in social situations, but further evaluation will demonstrate lack of interhemispheric transfer of information - Unable to retrieve with one hand an object palpated with another

Chlorpheniramine

- 1st gen antihistamine that acts by blocking both central and peripheral H1 receptors - Can be sedating as it penetrates the BBB and can accumulate in the CNS - don't take with other sedating meds like diazepam

Loratadine

- 2nd gen antihistamine blocks peripheral H1 receptors - Does not enter CNS and does not cause drowsiness like 1st gen does

What are 3 drugs that affect purine synthesis? How?

- 6-mercaptopurine: inhibit de novo purine synthesis - Mycophenolate, Ribavirin: inhibit inosine monophosphate dehydrogenase

Minimal change disease

- 90% of cases of nephrotic syndrome in children - LM: normal; no immunoglobins on immunoflourescence - Usually triggered by respiratory infection, allergic reaction, insect sting, immunization (several weeks later) - Albumin loss due to loss of (-) charged basement membrane - specific protein loss (albumin) - Tx: corticosteroids

Entacapone

- A COMT Inhibitor that increases the bioavailability of Levodopa by inhibiting its peripheral methylation - Currently used to tx Parkinson's pts with motor fluctuations who are experiencing end-of-dose "wearing off" periods with levodopa/carbidopa therapy

Risedronate

- A biphosphonate medication used to tx osteoporosis by inhibiting mature osteoclast-mediated bone resorption - Biphosphonates have a chemical structure similar to pyrophosphate and attach to hydroxyapatite binding sites on bony surfaces; osteoclasts that resorb the bone take up the biphosphate and are ubable to adhere to more bony surfaces to continue resorption - Decrease osteoclast activity, induce osteoclast apoptosis, and decrease development/recruitment of osteoclast precursor cells --> increased bone mineral density

Trehalose dimycolate

- A cell wall component and major virulence factor of Myco TB - protects from being killed by macrophages and stimulates granuloma formation

Denosumab

- A human monoclonal Ab to the receptor activator of NF-kB ligand (RANKL), which is part of the TNF family and is required for osteoclast function

What would cause an abnormal increase in oxygen saturation from the right atrium to the right ventricle? What type of murmur would you hear?

- A left-to-right shunt, typically due to a ventricular septal defect - Murmur: holosystolic murmur over the left sternal border

Neprilysin

- A metalloprotease that inactivates several peptide hormones including bradykinin, glucagon, enkaphalins, and natriuretic peptides

What is Dynein? What is its role in HSV?

- A microtubular motor protein that participates in retrograde axonal transport - Important in establishing latent HSV infection as it transports viral particles to the neural sensory ganglia (not involved in recurrence)

Follicular lymphoma - what is the chromosomal translocation? What is the abnormal gene expression?

- A non-Hodgkin lymphoma of the cleaved and noncleaved B-lymphocytes of the follicular center - Classic cytogenic abnormality is the t(14;18) translocation --> moves Bcl-2 protooncogene from chromosome 18 to chromosome 14, near the site of the immunoglobulin heavy chain enhancer element

Lambert-Eaton myasthenic syndrome

- A paraneoplastic disorder commonly associated with small cell lung cancer that clinically resembles myasthenia gravis - associated with a preexisting malignancy - Weakness of the proximal mm that improves during the day and with exercise - Antibodies against pre-synaptic calcium channels - Incremental response with nerve stimulation studies and no improvement with the Tensilon test

Amphotericin B - What is it? Mechanism of action? Side effects?

- A polyene macrolide antifungal medication that binds ergosterol (a sterol uniwue to fungi) - It creates pores in the fungal cell membrane allowing electrolytes to escape and disrupting cellular homeostasis - Adverse effects: nephrotox, hypokalemia, hypomagnesemia, and renal tubular acidosis

Molluscum contagiosum - What is it? What does it look like on LM? Exam?

- A poxvirus - Causes eosinophilic cytoplasmic inclusions (molluscum bodies) in infected cells - Exam: Dome-shaped, umbilicated papules

Medulloblastoma

- A primary brain tumor seen in kids - Cerebellar tumor that can compress the 4th ventricle --> non-communicating hydrocephalus - Homer-Wright rosette: circumferential pattern of cells

Craniopharyngioma

- A primary brain tumor seen in kids - From Rathke's pouch - May compress the optic chiasm

Ependymoma

- A primary brain tumor seen in kids - Perivascular rosette: seen around a blood vessel

Biliary atresia

- A progressive, complete or partial obstruction of extrahepatic bile ducts - the biliary tree is normal at birth and subsequently undergoes destruction that is thought to be immune-related or viral-induced - Infants may appear healthy at birth, but then present with jaundice within the first two months of life, along with dark urine and acholic (pale or clay-colored) stools due to excessive renal excretion of bilirubin and lack of intestinal bile, respectively - Phys Exam: hepatomegaly due to inflammation - Lab findings: elevated direct bilirubin and gamma-glutamyl transferase - Dx: liver biopsy - reveals intrahepatic bile duct proliferation, portal tract edema, and fibrosis - Tx: urgent surgical intervention required - lack of intervention can lead to death due to cirrhosis within 2 years

Calcineurin - why is it important? what meds inhibit it?

- A protein phosphatase that is activated upon stimulation of the appropriate cells receptor - once activated, calcineurin dephosphorylates nuclear factor of activated T cells (NFAT), which allows NFAT to enter the nucleus and bind to an interleukin-2 (IL-2) promoter - IL-2 stimulates the growth and differentiation of T cells and is an important component of the immune response - Inhibited by cyclosporine and tacrolimus

Clozapine

- A second-generation antipsychotic that is reserved for pts with tx-refractory schizophrenia

Trazodone

- A sedating antidepressant most often used as a hypnotic to treat insomnia associated with depression or antidepressant tx - Associated with the rare, but serious, side effect of priapism - persistent erection of the penis for >4 hours and not associated with sexual excitement - if left untreated can result in damage to penile tissue and permanent erectile dysfunction -- Use with caution in pts with conditions that predispose them to priapism: sickle cell disease, multiple myeloma - Mechanism: antagonizes postsynaptic serotonin receptors and inhibits serotonin reuptake - has minimal effects on norepi and dopamine

Ubiquitin

- A small protein present in the cytoplasm and nucleus of all eukaryotes - Covalently attaches to various intracellular proteins to signal for their degradation by the proteosome

What is the foam stability test?

- A test used to measure fetal lung maturity - Amniotic fluid is added to several wells containing ethanol and then shaken. The foam stability index is the highest value well that contains a ring of stable foam

Doxepin

- A tricyclic antidepressant - Has anticholinergic effects (may worsen delirium) - May be used for the tx of insomnia in other settings

IgA nephropathy

- A type of nephritic syndrome - Berger disease - IgA deposits in the mesangium - Usually after respiratory or GI infection - Presents as gross hematuria that lasts several days - may be episodic, reoccurring every couple of months - LM: proliferation of mesangium - seen in most nephritic syndromes - IF: granular pattern in mesangium - Tx: corticosteroids

What attaches to the anterior intercondylar area of the tibia?

- ACL - Injury: typically results from sudden deceleration and direction change that involves valgus stress on the knee

Familial Hypercholesterolemia

- AD - Absent or defective LDL receptors - Increased LDL and cholesterol in the blood - Heterozygotes have cholesterol around 300mg/dL; homozygotes (very rare) have around 700+ mg/dL - Accelerated atherosclerosis (may have MI before age 20), tendon (Achilles) xanthomas, and corneal arcus

Myotonic type 1 muscular dystrophy

- AD - CTG trinucleotide repeat expansion in the DMPK gene --> abnormal expression of myotonin protein kinase --> myotonia, muscle wasting, cataracts, testicular atrophy, frontal balding, arrhythmia

Hypertriglyceridemia

- AD - Hepatic overproduction of VLDL - Increased VLDL and TGs in blood - Hypertriglyceridemia (> 1000 mg/dL) can cause acute pancreatitis

Factor V Leiden gene mutation - what is the mutation? what is a sign?

- AD - Inherited thrombophilia that leads to the inability of activated Protein C to cleave and degrade factor V (a procoagulant) - Signs: family hx of early thrombosis

Von Hippel-Lindau disease

- AD - Mutation in the VHL tumor suppressor gene on chromosome 3 - Characteristics: hemangioblastomas in the cerebellum, cysts in the kidneys and pancreas, pheochromocytoma, and renal cell carcinoma (clear cell) - Also possible: polycythemia resulting from erythropoietin production by renal tumors

Peutz-Jeghers Syndrome - what is the classic sign? what is the mutation? What are these pts at increased risk for?

- AD - Mutations in serine/threonine kinase 11 (STK 11) gene on Ch 19 - Signs: pigmented mucocutaneous macules and numerous hamartomatous polyps in the GI tract --> abdominal pain and GU bleeding resulting from intussusception, obstruction or malignant transformation - Skin lesions are not present at birth - commonly appear on lips, buccal mucosa, hands and feet - Typically benign; associated with increased risk of breast and GI cancers

Hypertrophic cardiomyopathy - What is presentation? Mutation? What problems does it cause to the heart? What do coronary aa look like? What murmur is heard?

- AD - Sudden death in adolescents and young adults following severe exertional activity - Mutation: beta-myosin heavy chain protein as well as other defects in myofilament proteins - Inappropriate hypertrophy of LV myocardium and disordered arrangement of cardiac myofibrils - Causes diastolic dysfunction due to LV wall rigidity and decreased LV volume; as well as LV outflow obstruction --> increased afterload - Coronary arteries are unaffected - Murmur: systolic crescendo-decrescendo murmur heard between apex and left sternal border, radiating to the suprasternal notch - result of the LV outflow obstruction - becomes quieter with increases in preload or afterload and louder with decreases in preload or afterload (made louder by standing)

What mutation is associated with hypertrophic cardiomyopathy?

- AD - beta-Myosin heavy chain mutation

Adenosine deaminase deficiency

- ADA is required for degradation of adenosine and deoxyadenosine - In ADA def, there is increased dATP --> toxicity in lymphocytes - A major cause of SCID

Homocystinuria - What is the mutation? What are signs? What other disease does it look like? How do you distinguish the two diseases?

- AR - Cystathionine-beta-synthase gene mutation (CBS) - essential for the degradation of the amino acid methionine; deficiency --> inability to form cystein from homocysteine and a buildup of both methionine and homocysteine - Signs: marfanoid features - tall, thin, arachnodactyly, joint and skin hyperlaxity - Distinguishes from Marfan's syndrome: intellectual disability (marfan's does not have ID), hypercoagulability, downward dislocated lens (lens is upwardly dislocated in Marfan's)

Hartnup Disease

- AR - Def of neutral amino acid (ex. tryptophan) transporters in proximal renal tubular cells and on enterocytes --> neutral aminoaciduria and decreased absorption from the gut --> decreased tryptophan for conversion to niacin --> pallagra like symptoms - Tx: high protein diet and nicotinic acid

I-cell disease

- AR - Defects in protein targeting - mannose residues are not phosphorylated and are not able to be directed toward the lysosomes - Features: failure to thrive, cognitive defects in first year of life, coarse facial features, corneal clouding - Typically fatal in childhood

Hyperchylomicronemia

- AR - Lipoprotein lipase or C-11 deficiency - Increased chylomicrons, TG, and cholesterol in the blood - Findings: pancreatitis, hepatosplenomegaly, and eruptive/pruritic xanthomas (no increased risk for atherosclerosis) - Creamy layer in supernatant

Neimann-Pick Disease

- AR - Sphingomyelinase deficiency (responsible for the breakdown of sphingomyelin) --> sphingomyelin accumulation within the lysosomes - Cell appear enlarged, foamy, and vacuolated on EM (Lipid laden foam cells) --> accumulate in the spleen and liver --> hepatosplenomegaly - Hypotonia and neuro degeneration - Cherry red spot on macula

Friedreich Ataxia: what are some features? What is most common cause of death?

- AR - Typically presents during childhood/adolescence with progressive gait ataxia (due to degeneration of the spinocerebellar tracts) and impaired joint and vibration sense (due to degeneration of the posterior columns and dorsal root ganglia) - lateral corticospinal tract involvement may results in spastic mm weakness and a positive Babinski sign - Other features: hypertrophic cardiomyopathy, skeletal abnormalities, and diabetes mellitus - Most common cause of death: complications from cardiomyopathy (cardiac arrhythmias, congestive heart failure)

Medium-chain acyl CoA dehydrogenase deficiency

- AR disorder of fatty acid oxidation - Decreased ability to break down fatty acids into acetyl-CoA --> accumulation of 8- to 10-carbon fatty acyl carnitines in the blood and hypoketotic hypoglycemia - May present in infancy or early childhood with vomiting, lethargy, seizures, coma, and liver dysfunction - Minor illness can lead to suden death - Tx: avoid fasting

What is the mutation in Friedreich ataxia?

- AR trinucleotide repeat (GAA) on Ch9 in gene that encodes frataxin (iron binding protein) --> impairment of mitochondrial functioning

Spinal stenosis

- Abnormal narrowing of the spinal canal, most commonly in the lumber region - Lower extremity pain, numbness/paresthesia, and weakness - Symptoms are postural dependent** (worse with extension of the spine, better with leaning forward) - Most common cause: degenerative arthritis of the spine --> formation of facet joint osteophytes and hypertrophy of the ligamentum flavum

What is the underlying defect in Cystic Fibrosis?

- Abnormal post-translational processing of a transmembrane protein - Most common CFTR mutation is a 3-base pair deletion of phenylalanine at amino acid position 508 --> impaired post-translational processing of CFTR, which is detected by the endoplasmic reticulum --> the protein is targeted for proteosomal degradation - Characterized by recurrent sinopulmonary infections, pancreatic insufficiency, and malabsorption

myotonic dystrophy

- Abnormally slow relaxation of muscles - difficulty loosening one's grip after a handshake or inability to release the doorknob - AD; due to abnormal trinucleotide repeat (CTG) of the gene that codes for the myotonia-protein kinase - Displays anticipation - Cataracts, frontal balding and gonadal atrophy are common

Classic Galactosemia

- Absence of galactose-1-phosphate uridyltransferase - AR - Damage is caused by accumulation of toxic substances (including galactitol, which accumulates in the lens of the eye) - Symptoms: failure to thrive, jaundice, hepatomegaly, infantile cataracts, ID - Can lead to E Coli sepsis in neonates - Tx: exclude galactose and lactose (galactose + glucose) from diet

Pemphigus Vulgaris - what is it? What does it look like on IF? What is the immune target?

- Acantholysis forming suprabasal blisters - IF: deposition of IgG-containing deposits in a reticular pattern around keratinocytes - Immune target: desmosome protein desmoglein

How do you treat an OD of an acidic drug? Basic drug?

- Acidic drug: tx with NaHCO3 --> alkalizes urine (increases pH) which then traps acidic drugs in the urine - Basic drug: tx with NH4Cl --> acidifies the urine (decreases pH) which then traps basic drugs in the urine

Fibrates

- Activates PPAR-alpha and decreases VLDL synthesis - Decreases triglycerides and increases HDL - Side effects: muscle toxicity, gallstones

IFN-gamma

- Activates macrophages, increases MHC expression, and promotes Th1 differentiation - Produced by T cells and NK cells - Critical in immunity against viral and intracellular bacterial infections

What type of receptor does IGF-1 act on? What does it do?

- Acts on tyrosine kinase receptors - stimulates cell growth and proliferation in bone, cartilage, skeletal mm, and other soft tissues

Excess Vit A: Acute tox, chronic tox

- Acute Tox: nausea, vomiting, vertigo, blurred vision - Chronic tox: alopecia, dry skin (scaliness), hepatotoxicity and enlargement, arthralgias, pseudotumor cerebri

Erythema multiforme - What is it? What causes it? Pathophysiology?

- Acute inflammatory disorder that can involve skin of the extremities, face, trunk, and neck - severe cases may also affect oral mucous membranes and the tongue - A cell-mediated immune process with an inflammatory infiltrate predominated by cytotoxic CD8+ lymphocytes - Usually associated with infections, such as herpes simplex virus and mycoplasma, and may be an immune response against antigens deposited in the skin - Can also be seen with certain medications (sulfonamides), malignancy, and collagen vascular disease

What biochemical changes occurs in the CNS due to alcohol use?

- Acutely: potentiates the effects of GABA via GABA-A receptors - Chronically: causes downregulation of GABA receptors - Weakly inhibits excitatory NMDA receptors in the brain - chronic use upregulates these receptors

What is the most common enzymatic defect that leads to hypoketonic hypoglycemia after a period of fasting?

- Acyl-CoA Dehydrogenase deficiency --> impaired fatty acid beta-oxidation in the mitochondria - Carnitine def: prevents fatty acids from being transported into the mitochondria for beta-oxidation and causes similar features - Usually asymptomatic in both until the pt experiences a significant fast

What diseases are HLA-B8 associated with?

- Addison's disease, Myasthenia gravis

What maintains blood glucose levels after 3 days of starvation?

- Adipose stores (ketone bodies become the main source of energy for the brain) - after these are depleted, vital protein degradation accelerates leading to organ failure and death - Amount of excess stores determines survival at the time

What patient characteristic is most likely to indicate a poor long-term prognosis for pts with post-strep glomerulonephritis?

- Adult onset: only 60% recover completely (95% children recover), and the rest develop chronic hypertension, recurrent proteinuria, chronic renal insufficiency, or rapidly progressive GN - Pre-existing kidney disease is another poor prognostic factor

How do you prevent nephrotoxicity when giving a pt Acyclovir?

- Aggressive IV hydration and dosage adjustment, which includes slowing the rate of IV infusion

Fabry disease

- Alpha-galactosidase A deficiency - Globotriaosylceramide (ceramide trihexoside) accumulation - Clinical manifestations begin in childhood with neuropathic pain and dermatologic pathology (telangiectasias, angiokeratomas)

What is the classic triad of IgA-mediated vasculitis?

- Also known as Henoch-Schonlein Purpura - Triad: Palpable purpura on buttocks/legs, Arthralgias, Abdominal pain

Signs of increased intracranial pressure in newborn

- Altered mental status - Enlarging head circumference - Bulging fontanel - Downward driven eyes - May be due to Vit K def --> intracranial hemorrhage

Primary ovarian insufficiency - what is it? causes?

- Amenorrhea in women <40yo with elevated gonadotropins (FSH) and low estrogen - Pathophysiology: inadequate supply of ovarian follicles or premature depletion of these follicles

What medications are used to treat Cryptococcal meningitis?

- Amphotericin B: most effective even though it has low CSF penetration - Flucytosine: Used during initial induction period - Fluconazole: Used for long-term maintenance therapy

What mutations are associated with Alzheimer disease?

- Amyloid precursor protein (APP) gene on Ch 21 - Presenilin 1 gene on Ch 14 - Presenilin 2 gene on Ch 1 - ApoE4: thought to be involved in the formation of senile plaques

Pancoast tumor - What is it? What does it cause? How does it cause that?

- An Apical bronchogenic carcinoma that invades the brachial plexus - the most common cause of Horner syndrome - Horner syndrome: sympathietic nerve supply to the head, eyes and neck is interrupted - effected by pancoast tumor due to compression of the superior cervical ganglion

What is the initial drug of choice for treating status epilepticus?

- An IV Benzodiazepine (such as Lorazepam): effective and rapid onset of action - Enhance the effect of GABA at the GABA-A receptor --> increased influx of chloride ions in response to GABA binding

L-selectin

- An adhesion molecule that aids entry of lymphocytes from the blood into lymphoid tissue and margination of neutrophils during the inflammatory process

Sorbitol

- An alternative method of trapping glucose is to convert it to its alcohol counterpart, sorbitol, via aldose reductase - Some tissues convert sorbitol --> fructose using sorbitol dehydrogenase --- Tissues with insufficient amounts of this enzyme are at risk for intracellular sorbitol accumulation --> osmotic damage (cataracts, retinopathy, and peripheral neuropathy seen with chronic hyperglycemia in DM)

Clomiphene citrate

- An anti-estrogen med that stimulates ovulation by blocking the feedback inhibition of estrogen on the hypothalamus --> increases release of pituitary gonadotropins - Used to achieve fertility in women with ovulatory failure who are normogonadotropic, normoprolactinemic, and euthyroid

Mebendazole

- An anti-helminthic drug that acts on the microtubules of roundworms like Ancylostoma, Ascaris, and Enterobius

Buproprion

- An antidepressant that inhibits the reuptake of norepinephrine and dopamine - Does not cause weight gain or sexual side effects - SEIZURES are the potential side effect - especially in pts with a pre-existing seizure or eating disorder

G6PD

- An enzymes of the pentose phosphate pathway that in erythrocytes is essential for maintaining adequate concentrations of NADPH

Pulsus paradoxus

- An exaggerated drop (>10mmHg) in systolic blood pressure during inspiration - Korotkoff sounds: the difference between the systolic pressure in which these sounds first become audible during expiration and the pressure at which they are audible throughout all phases of respiration quantifies pulsus paradoxus (see pic) - Caused by conditions that impair expansion into the pericardial space (acute cardiac tamponade, pericardial disease)

McCune-Albright syndrome

- An example of mosaicism - Due to mutation affecting G protein signaling - Presents with unilateral cafe-au-lait spots, polyostotic fibrous dysplasia, precocious puberty, multiple endocrine abnormalities - Lethal mutation if occurs before fertilization (affects all cells) but survival occurs in pts with mosaicism

Gilbert Syndrome

- An inherited, benign condition of reduced production of glucuronyl transferase, a hepatic enzyme responsible for glucuronidation - Pts usually asymptomatic except at times of stress (fasting, illness) during which mild, indirect hyperbilirubinemia and jaundice are present

Osgood-Schlatter Disease

- An overuse injury of the secondary ossification center (apophysis) of the tibial tubercle - Presentation: pain and swelling of the tibial tubercle, the insertion point of the patellar ligament, which is connected to the quad mm (involved in knee extension) - Repetitive quad contraction (jumping) and chronic avulsion cause the proximal patellar tendon to separate from the tibial tubercle - During the healing process, callous formation causes the tubercle to become elevated and prominent

What is the best lab method to determine if a gene is being expressed?

- Analyze for the presence of its mRNA using the Northern blot method

What are anaplastic tumors? What are the 5 features they typically demonstrate?

- Anaplastic tumors: demonstrate complete lack of differentiation - Features: 1) Loss of cell polarity with complete disruption of normal tissue architechture; cells coalesce into sheets of islands in a disorganized, infiltrative fashion 2) Significant variation in the shape and size of cells (cellular pleomorphism) and nuclei 3) Disproportionately large nuclei that are often deep staining with abundant, coarsely-clumped chromatin and large nucleoli 4) Numerous, often abnormal, mitotic figures 5) Giant, multinucleated tumor cells

Anatomic vs alveolar dead space

- Anatomic dead space: dead space of the conducting airways (normally ~150mL) - Alveolar dead space: due to well-ventilated but poorly perfused alveoli - Physiologic dead space: anatomic dead space + alveolar dead space

What causes Weber syndrome? What are the symptoms?

- Anterior midbrain infarction resulting from the occlusion of the paramedian branches of the posterior cerebral artery - Cerebral peduncle lesion: dysphagia, dysphonia, dysarthria (corticobulbar tract damage); Contralateral spastic hemiparesis (corticospinal tract damage) - Oculomotor nerve palsy --> ipsilateral ptosis, pupillary dilation, and lateral strabismus (eye looks down and out)

What direction do HSV particles move on the axon during reactivation? What motor protein mediates this movement?

- Anterograde axonal transport - Mediated by Kinesin - moves things away from the nucleus, down the axon, towards the nerve terminal

What is tx for post-strep GN?

- Anti-hypertensives, salt/water restriction and diuretics for edema

Thymus-dependent antigens

- Antigens containing a protein component (ex. diphtheria vaccine) - Class switching and immunologic memory occur as a result of direct contact of B cells with Th Cells (CD40-CD40L interaction)

Thymus-independent antigens

- Antigens lacking a peptide component (lipopolysaccharides from gram - bacteria); cannot be presented by MHC to T cells - Weak immunogenic; vaccines often require boosters and adjuvants (ex. pneumococcal polysaccharide vaccine)

Function of Vit A

- Antioxidant, constituent of visual pigments, essential for normal differentiation of epithelial cells into specialized tissue (pancreatic cells, mucus-secreting cells); prevents squamous metaplasia - Used to tx measels and AML subtype M3 - Used to tx acne 0 Found in liver and leafy vegetables

Where is CSF absorbed and returned back to venous circulation?

- Arachnoid villi - Absorption is decreased in communicating hydrocephalus and normal pressure hydrocephalus

What are the basic amino acids?

- Arginine (Arg), Lysine (Lys), Histidine (His) - Arg is most basic - Has no charge at body pH

Craniopharyngiomas

- Arise from remnants of Rathke's pouch - Typically located in the suprasellar region - Presentation: hypothalamic or pituitary dysfunction and changes in vision due to disruption of optic chiasm

Lateral femoral cutaneous n

- Arises from L2-L3 n root - Provides sensation to skin on the lateral thigh

Obturator n

- Arises from L2-L4 n roots - Innervates skin of the medial thigh - Provides motor function for the adductor mm of the lower extremity

Femoral n

- Arises from L2-L4 n roots - Provides sensation to the upper thigh and inner leg - Innervates mm that extend the knee

Iliohypogastric n - What root does it arise from? What branch is at risk of being damaged during surgery? What surgery? What would be the symptoms?

- Arises from the L1 nerve root --> lateral border of the upper psoas major --> passes behind the kidney anterior to the quadratus lumborum - Provides motor function to the anterolateral abdominal wall muscles - The anterior branch emerges above the superficial inguinal ring to innervate the skin above the pubic region - may be injured during APPENDECTOMY --> decreased sensation at the suprapubic region - The lateral branch descends over the iliac crest to innervate the gluteal region

Function of Vit C

- Ascorbic acid - Antioxidant - Facilitates iron absorption by reducing it to Fe2+ state - Necessary for hydroxylation of proline and lysine for collagen synthesis - Necessary for dopamine beta-hydrozylase which convert dopamine to NE - Found in fruits and veggies

What are the acidic amino acids?

- Aspartic acid (Asp), Glutamic acid (Glu) - Negatively charged at body pH

Small cell lung carcinoma

- Associated with smoking and is usually centrally located - Arises from primitive cells of the basal layer of the bronchial epithelium - Light microscopy: round or oval cells with scant cytoplasm and large hyperchromatic nuclei; cells can forms sheets or clusters and abundant mitoses are usually seen - Can display varying degrees of neuroendocrine differentiation - Stains: positive for neuroendocrine markers, such as neuron-specific enolase, chromogranin, and synaptophysin - Electron microscopy: some of the cells are found to have secretory granules in the cytoplasm

Where does blunt aortic injury most likely occur?

- At the aortic isthmus, which is tethered by the ligamentum arteriosum and is relatively fixed compared to the adjacent aorta - Most pts die quickly, if survive symptoms include chest pain, back pain, and shortness of breath - Widened mediastinum may be seen on CXR - The aortic isthmus is the area labeled C in the picture

Eczema

- Atopic eczematous dermatitis - Intraepidermal vasicles, superficial epidermal hyperkeratosis producing scales, epidermal hyperplasia (acanthosis) and/or chronic inflammatory infiltrate within the dermis - In successful tx, might see these findings on histo: atrophy of the dermis with loss of dermal collagen, drying, cracking, and/or tightening of the skin, telangiectasias, ecchymoses from mild trauma, and atrophic striae

What is seen on imaging in pts with Huntington Disease?

- Atrophy of the caudate - Metabolic imagining studies, such as PET scan, show decreased metabolic activity in the striatum, which is composed of the caudate and the putamen

What is the treatment of choice for organophosphate poisoning?

- Atropine

Autoimmune gastritis

- Autoantibodies against gastric parietal cells --> inflammation of the gastric mucosa, parietal cell destruction and achlorhydria - Leads to Vit B12 deficiency

Antiphospholipid antibody syndrome

- Autoimmune disorder (commonly secondary to SLE; but can be primary) - Dx: history of thrombosis or spontaneous abortion, lab findings of SLE anticoagulant, anticardiolipin, anti-beta2 glycoprotein antibodies - Tx: systemic anticoagulation - ****Prolonged PTT and false-positive VDLR/RPR - Prolonged coagulation times in vitro but coagulation in vivo

What's the most important prognostic factor in early-stage breast cancer?

- Axillary lymph node involvement

What structures can be damaged in an anterior shoulder dislocation?

- Axillary nerve (sensation to the deltoid area) and posterior circumflex artery - Supraspinatus tendon - Anterior glenohumeral ligaments and glenoid labrum separation from the articular surface of the anterior glenoid neck (AKA Bankart lesion) - Posterolateral humoral head defect due to forceful impact against the anterior rim of the glenoid (AKA Hills-Sachs lesion)

Describe the intrinsic pathway of apoptosis

- Bcl-2 is the major anti-apoptotic regulator of mitochondrial permeability - DNA damage or apoptotic signal activates BAX (pro-apoptotic) - BAX creates channels in the mitochondrial membrane - Cytochrome C moves from the mitochondria into the cytosol and activates caspases - Caspases are the primary initiator of apoptosis

Why is Heparin safer to use in pregnancy than warfarin?

- Because it has a high water solubility - can't cross the placenta

Common medications to avoid in older adults (chart)

- Beers criteria: IDs drugs that should be used with caution in geriatric pts

Describe the process of bacterial killing by neutrophils

- Begins with extravasation into the infected tissues in response to increased expression of cell adhesion molecules on the inflamed endothelium - Next, the neutrophils migrate toward the bacteria, guided by chemotactic factors such as IL-8, C5a, and bacterially produced formyl peptides - On contact with offending organisms, receptors on the neutrophils bind bacterial antigens and host opsonins (Abs, C3b), triggering phagocytosis - NADPH OXIDASE, a membrane protein on the phagosome, becomes activated once the bacteria have been engulfed - this enzyme catalyzes the first step of the oxidative burst pathway, transferring an electron from NADPH to molecular O2 and forming the reactive oxygen species SUPEROXIDE --> directly damages the bacterial membrane through lipid peroxidation or it may spontaneously react with water to form hydrogen peroxide - In addition, fusion of azurophilic granules with the phagosome introduces proteases, defensins, and myeloperoxidase that aid in microbial killing - Myeloperoxidase: combines hydrogen peroxide and chloride ions to produce hypochlorous acid (bleach), which is many times more potent a destructive agent than hydrogen peroxide

What neurological event is associated with adult polycystic kidney disease?

- Berry aneurysm

What is polycystic kidney disease associated with?

- Berry aneurysms

What is usually used to tx acute obstructive pulmonary exacerbations (COPD/asthma exacerbations)?

- Beta-2 agonists - Works via Gs protein-coupled receptor that activates adenylyl cyclase and increases intracellular cAMP concentrations - Corticosteroids may be used but do not provide immediate relief - take several hours to a few days to take effect - impair eosinophil degranulation

Gaucher disease

- Beta-glucocerebrosidease deficiency - Glucocerebroside accumulation - Hepatosplenomegaly, pancytopenia, and skeletal problems

Tay-Sachs disease

- Beta-hexosaminidase A deficiency - Accumulation of GM2 in neurons --> neurologic regression and cherry-red macula - **NO hepatosplenomegaly**

Why are the peroxisomes important?

- Beta-oxidation of very long chain fatty acids and branched chain fatty acids - Synthesis of plasmalogens - important phospholipids found in myelin (neural tissue) - Oxidases and catalase for metabolizing ethanol and other toxic substances

Neurofibromatosis type 2

- Bilateral acoustic schwannomas, juvenile cataracts, meningiomas and ependymomas - Mutation in NF2 gene on Ch 22

AD Polycystic Kidney Disease

- Bilateral massive enlargement of kidneys due to multiple large cysts - Mutation in PKD1 on Ch 16 - Few due to mutation in PKD2 on Ch 4

Cyclosporin - What is the mechanism of action? What is it used for?

- Binds intracellularly to cyclophilin, forming a complex that inhibits calcineurin --> inhibits IL-2 gene transcription (does not directly affect the IL-2 receptor) - Used as an immunosuppressant, as needed with translantation pts

What does Protein A on Staph Aureus do?

- Binds with the Fc portion of IgG Abs at the complement-binding site - preventing complement activation --> decreased production of C3b --> impaired opsonization and phagocytosis

Vit B7 def

- Biotin - Rare - Dermatitis, alopecia, enteritis - Caused by antibiotic use or excessive ingestions of raw egg whites

Maple syrup urine disease

- Blocked degradation of branched amino acids (Isoleucine, Leucine, Valine) due to decreased branched-chain alpha-ketoacids in blood, especially those of leucine - Severe CNS defects, ID, and death - Tx: restriction of isoleucine, leucine, valine in diet, and thiamine supplementation - Autosomal Recessive - Presentation: vomiting, poor feeding, urine smells like maple syrup/burnt sugar

Phenytoin

- Blocks presynaptic voltage-gated sodium channels and can be used to prevent recurrence of status epilepticus dur to its long duration of action - Has a slow onset of action and should not be used as initial tx

Gabapentin

- Blocks voltage-gated calcium channels --> attenuating excitatory neurotransmitter release

Epidural hematoma

- Blood between skull and dura mater - Usually associated with fracture of the temporal bone and subsequent rupture of the middle meningeal artery - Pt loses consciousness at time of impact --> regains consciousness for a lucid interval --> quick decline in mental function --> coma/death - Dx: CT without contrast - lens shaped

What does C3a do? C3b?

- Both are components of complement and are split from C3 - C3a: helps recruit phagocytic cells and induce inflammation - C3b: acts as opsonin, and can bind reversibly to C3b convertase and form C5 convertase, ultimately triggering the membrane attack complex

What's important about Arginine (Arg) and Histidine (His)?

- Both are required during periods of growth - Arg and Lys are increased in histones, which bind negatively charged DNA

Hereditary hemorrhagic telangiectasia

- Branching skin lesions, recurrent epistaxis, skin discolorations, arteriovenous malformations, GI bleeding, hematuria - Also known as Osler-Weber-Rendu syndrome

Entrapment of nerves from fascia closure during surgery causes what symptom?

- Burning/sharp pain due to continuous stimulation of pain fibers

How does Digoxin improve systolic heart failure symptoms?

- By increasing ventricular contractility: Digoxin inhibits the Na/K pump --> increased intracellular Na+ --> increased intracellular Ca2+ which enhances excitation-contraction coupling and allows maximal cross-linking of actin and myosin for greater contractility

How do CDKs and Cyclins work?

- CDKs: constitutive and inactive (activated by cyclins) - Cyclins: regulatory proteins that control cell cycle events; phase specific; activate CDKs - Complexes: phosphorylate other proteins to coordinate cell cycle progression; must be activated and inactivated at the appropriate times for the cell cycle to progress

Fragile X syndrome

- CGG repeat on FMR1 gene --> methylation --> decreased expression - X-linked dominant - Second most genetic cause of ID - Post-pubertal macroorchidism (enlarged testes), long face with a large jaw, large everted ears, autism, mitral valve prolapse

What meds may cause Steven-Johnsons syndrome as a side effect?

- CLAPPPERS - Carbamazepine, Lamotrigine, Allopurinol, Phenytoin, Phenobarb, Penicillin, Ethosuximide, RASH, Sulfa drugs

COP1 vs COP2 vs Clathrin

- COP1: Golgi --> Golgi (retrograde movement); cis-Golgi --> ER - COP2: ER --> cis-Golgi (anterograde movement) - Clathrin: trans-Golgi --> lysosomes; plasma membrane --> endosomes (receptor mediated endocytosis)

What substances are P450 inhibitors?

- CRACK AMIGOS - Ciprofloxacin, Ritonavir (protease inhibitor), Amiodarone, Cimetidine, Ketoconazole, Acute alcohol use, Macrolides, Isoniazid, Grapefruit juice, Omeprazole, Sulfonamides

What effects do inhaled anesthetics have on the CV system? Respiratory system? Brain? Kidneys? Hepatic blood flow?

- CV system: myocardial depression that leads to decreased cardiac output and an increase in atrial and venous pressures, hypotension also results - Respiratory system: depresses the respiratory system, decreases tidal volume and minute ventilation and cause hypercapnia, suppresses mucociliary clearance; Halothane and secoflurane have bronchodilation properties and are preferred in asthma pts - Brain: decrease vascular resistance --> increased cerebral blood flow --> increased intracranial pressure (undesirable) - Kidneys: decrease GFR, increase renal vascular resistance and decrease renal plasma flow - Hepatic blood flow: decrease

Neurofibromatosis type 1

- Cafe-au-lait spots, cutaneous neurofibromas, optic gliomas, pheochromocytomas, Lisch nodules (pigmented iris hamartomas) - 100% penetrance, variable expression - Mutations in NF1 gene on Ch 17

S3 heart sound - What does it mean? When is it best heard? When does it occur?

- Can be a normal finding in healthy children and young adults - In pts over 40 it is considered abnormal and suggests ventricular enlargement - May be heard in pts with chronic severe mitral regurgitation, chronic aortic regurgitation, and heart failure associated with dilated or ischemic cardiomyopathy - Occurs during diastole shortly after the second heart sound - Heard best while pt is lying in the left lateral decubitus position at the end of expiration - due to decreasing lung volume and bringing the heart closer to the chest wall

Hyperammonemia

- Can be acquired (liver disease) or hereditary (urea cycle enzyme deficiencies) - Results in excess NH3, which depletes alpha-ketoglutarate, leading to inhibition of TCA cycle - Tx: limit protein in the diet - May be given to decrease ammonia levels: --- Lactulose to acidify the GI tract and trap NH4+ for excretion --- Rifaximin to decrease colonic ammoniagenic bacteria --- Bezoate, phenylacetate, or phenylbutyrate to bind NH4+ and lead to excretion

Pathology of emphysema

- Can be caused by alpha1-antitrypsin deficiency --> excess elastase activity

What does complement C5a do?

- Can enhance phagocytosis by macrophages by binding to receptors on the phagocytes and stimulating them directly - Potent chemotactic agent: draws more neutrophils and monocytes to the site of inflammation

Cardiac sarcoidosis

- Can present with restrictive or dilated cardiomyopathy along with conduction defects and atrial or ventricular arrhythmias - Sudden death can occur - Microscopy: presence of noncaseating granulomas containing giant cells

Pulsatile GnRH infusion - when is it used? What must be working for this method to work?

- Can stimulate ovulation in women who have disordered hypothalamic GnRH secretion resulting in hypogonadotropic, hypogonadal anovulation - Pituitary and ovarian function must be intact for this method to work

Pts receiving parenteral nutrition (through a central venous catheter) are at high risk for what?

- Candidemia: Candida inthe bloodstream - Morphology: branching pseudohyphae with blastoconidia

What are the 3 layers of the blood brain barrier?

- Capillary endothelial layer with tight junctions - Basement membrane - Astrocyte foot processes

What is the rate limiting enzyme of the urea cycle? What does deficiency of this enzyme look like?

- Carbamoyl phosphate synthase 1 (CPS1) - Def: severe hyperammonemia and neurological damage

Myocardial Infarction Complications

- Cardiac arrhythmia: First few days after MI; important cause of death before reaching hospital within first 24 hours - Postinfarction fibrinous pericarditis: 1-3 days after MI; Friction rub - Papillary m rupture: 2-7 days after MI; Can result in severe mitral regurgitation - Interventricular septal rupture: 3-5 days after MI; Macrophage mediated degradation --> VSD - Ventricular pseudoaneurysm formation: 3-14 days after MI; Contained free wall rupture; decreased cardiac output, risk of arrhythmia, embolus from mural thrombus - Ventricular free wall rupture: 5-14 days after MI; free wall rupture --> cardiac tamponade - True ventricular aneurysm: 2 weeks - several months after MI; outward bulge with contraction (dyskinesia) associated with fibrosis - Dressler syndrome: several weeks after MI; autoimmune phenomenon resulting in fibrinous pericarditis - LV failure and pulmonary edema: Can occur secondary to LV infarction, VSD, free wall rupture, papillary mm rupture with mitral regurgitation

Chronic granulomatous disease

- Catalase-positive organisms such as Staph aureus are phagocytosed but cannot be killed effectively - Pts experience recurrent suppurative infections (abscesses)

Desmolase

- Catalyzes the conversion of cholesterol to pregnenolone, which is the first step in the synthesis of steroid hormones

What are the phases of pertussis?

- Catarrhal phase: similar to many routine upper respiratory infections - malaise, mild fever, rhinorrhea - Paroxysmal phase: marked by severe coughing spells with the classic inspiratory whoop or post-tussive emesis (vomiting) - Convalescent phase: cough improves

Proprionic acidemia

- Caused by a congenital deficiency of propionyl-CoA carboxylase: catalyzes the conversion of propionyl-CoA --> methylmalonyl-CoA - Excess proprionic acid accumulates in the bloodstream --> severe metabolic acidosis - Hypoglycemia and ketosis frequently develop secondary to the acidosis - Present 1-2 weeks after birth with lethargy, poor feeding, vomiting and hypotonia - Tx: low-protein diet containing minimal amounts of valine, isoleucine, methionine and threonine

What are some of the defects that can cause gout?

- Caused by tissue deposition of monosodium urate crystals - Increased purine metabolism may lead to hyperuricemia, which is a risk factor for gout - Phosphoribosyl pyrophosphate (PRPP) synthetase is the enzyme responsible for the production of the activated ribose necessary for de novo synthesis of purine and pyrimidine nucleotides

Pyruvate dehydrogenase def

- Causes a buildup of pyruvate that gets shunted to lactate (via LDH) and alanine (via ALT) - X linked - Neurological defects, lactic acidosis, increased serum alanine starting at infancy - Tx: increase intake of ketogenic nutrients (high fat content or increased lycine and leucine)

Breast milk jaundice

- Causes indirect hyperbilirubinemia that peaks at age 2 weeks - Pathogenesis: usually involves the enzyme beta-glucuronidase which is in breast milk that deconjugates bilirubin --> increased absorption and, therefore, increased enterohepatic circulation of bilirubin - Urine and stool appearance are unaffected

Cardiac amyloidosis - what is it? What does biopsy look like? LM?

- Causes restrictive cardiomyopathy - Results from abnormal extracellular deposition of insoluble proteins such as monoclonal light chains (AL amyloidosis), mutated transthyretin (familial ATTR amyloidosis), or wild-type transthyretin (senile systemic amyloidosis) in myocardial tissue - Biopsy: Reveals cross-sections of normal myocardial cells with other areas of myocardium infiltrated by an amorphous and acellular pink material - LM: Congo red stain shows apple-green birefringence under polarized light

What disease is HLA-DQ2/DQ8 associated with?

- Celiac disease

Central vs. Nephrogenic Diabetes Insipidus

- Central: Inadequate production or release of Vasopressin at the hypothalamus-pituitary level - Nephrogenic: Impaired response to vasopressin reduces translocation of aquaporin-2 to the apical cell membrane --> reduced water resorption in the collecting ducts, even in states of water deprivation ---- Can be caused by Lithium use

Reassortment

- Changes in genomic composition that occur when host cells are coinfected with 2 segmented viruses that exchange whole genome segments - Causes sudden alterations of the viral progeny, as observed with the highly mutagenic influenza virus - **Viruses must be segmented**

Aortic regurgitation

- Characterized by an early diastolic murmur - Some may be asymptomatic; symptoms include palpitations or atypical chest pain, exertional dyspnea and fatigue (signs of left sided heart failure)

Hyaline arterioloscerosis

- Characterized by deposition of eosinophilic hyaline material in the intima and media of small arteries and arterioles - widespread narrowing of the renal arterioles with deposition of homogenous, glassy material in the subendothelial space that stains pink with PAS stain - Typically seen in pts with untreated or poorly controlled hypertension or diabetes mellitus - Chronic/repetitive endothelial injury from HTN or hyperglycemia causes leakage of plasma constituents across the vascular endothelium and stimulates smooth m cell proliferation and excessive extracellular matrix production

Dandy-Walker malformation

- Characterized by hypoplasia/absence of the cerebellar vermis and cystic dilation of the 4th ventricle with posterior fossa enlargement - Presentation: during infancy with developmental delay and progressive skull enlargement - Cerebellar dysfunction --> unsteadiness and impaired muscular coordination - May lead to non-communicating hydrocephalus due to atresia of the foramina of Luschka and Magendie --> elevated intracranial pressure --> irritability, vomiting - Other associated features: agenesis of the corpus callosum and malformations involving the face, heart or limbs

Acute eczematous dermatitis

- Characterized histologically by spongiosis, an accumulation of edema fluid in the intercellular spaces of the epidermis - the intercellular bridges becomes more distinctive and are described as spongy - A group of conditions characterized by erythematous, papulovascular, weeping lesions

Vit B2 Def

- Cheilosis (inflammation of the lips, scaling and fissures at the corners of the mouth), Corneal vascularization

Tx of Wilson disease

- Chelators (D-penicillamine, trientine) - Zinc: interferes with copper absorption

What part of the brain is responsible for the vomiting that occurs after chemotherapy?

- Chemoreceptor trigger zone: located on the dorsal surface of the medulla at the caudal end of the fourth ventricle in a region known as the AREA POSTREMA - The Area postrema received blood from fenestrated vessels (absent blood brain barrier), which allows it to sample chemicals circulating in the blood

Leukotriene B4

- Chemotactic agent - increases ability of leukocytes to cross from the serum into the tissues as part of the inflammation process

Cholesterol synthesis

- Cholesterol needed to maintain cell membrane integrity and to synthesize bile acid, steriods, and Vit D - Rate limiting step: catalyzed by HMG-CoA Reductase (inhibited by statins; induced by insulin) - converts HMG-CoA --> mevalonate - 2/3 of plasma cholesterol is esterified by lecithin-cholesterol acyltransferase (LCAT)

Amiodarone

- Class 3 antiarrhythmic drug (K+ channel blocker) - inhibit outward potassium currents during phase 3 of the cardiac action potential, prolonging repolarization and total action potential direction - Very little risk of Torsades

Gonococcal cervicitis

- Clinical features: purulent or mucopurulent discharge, friable cervix with easy bleeding (intermenstrual or postcoital bleeding) - Dx: Nucleic acid amplification testing - Tx: 3rd gen cephalosporin PLUS Azithromycin or doxycycline

What medications may be given to a PCOS pt who wishes to get pregnant?

- Clomiphene (or letrozole): Selective Estrogen Receptor Modulator that prevents negative feedback inhibition on the hypothalamus and pituitary by circulating estrogen --> increased LH and FSH --> ovulation

Structure of tRNA

- Cloverleaf form - Have CCA at the 3' end along with a high percentage of chemically modified bases - the amino acid is covalently bound to the 3' end of the tRNA - Acceptor stem: the 5'-CCA-3' is the amino acid acceptor site

Vit K function

- Cofactor for gamma-carboxylation of glutamic acid residues on various proteins required for blood clotting - Synthesized by intestinal flora - Needed for maturations of the clotting factors 2, 7, 9, 10, Protein C, and Protein S

Function for VIt B12

- Cofactor for methionine synthase (transfers methyl groups as methylcobalamin) and methylmalonyl-CoA mutase - Found in animal products - Def can be found in those with probs with absorption or vegans

In what virus are cryoglobulins seen?

- Cold-precipitable serum proteins that contain Igs -Seen in Hep C

Familial adenomatous polyposis

- Colon becomes covered with adenomatous polyps after puberty - Mutations in Ch 5q (APC gene)

Rotavirus

- Common cause of gastroenteritis in young children - Osmotic diarrhea by infecting and destroying small intestinal enterocytes --> loss of digestive enzymes (maltase, sucrase, lactase) --> malabsorption of complex sugars --> profuse watery diarrhea - Healing: new intestinal epithelial cells differentiate from stem cells that reside in the deepest portions of the Crypts of Lieberkuhn

Cheyne-Stokes breathing

- Commonly seen in pts with advanced CHF - Cyclic breathing pattern in which apnea is followed by gradualy increasing then decreasing tidal volumes until the next apneic period

What is glial fibrillary acid proteins a component of and why is it stained?

- Component of astrocytes, schwann cells, and other neuroglia - Stained to identify glioblastoma

What are neurofilaments a component of and why are they stained?

- Component of axons within neurons - Stained to ID neuroblastoma

What is Vimentin a component of and what is it stained to identify?

- Component of connective tissue (fibroblasts, leukocytes, endothelium) - Stained to ID sarcoma

Pigment Gallstones

- Composed of calcium salts of unconjugated bilirubin - Soft, dark brown/black - Typically arise secondary to bacterial infection of the biliary tract (E Coli) which results in the release of BETA-GLUCURONIDASE by injured hepatocytes and bacteria ---- This enzyme hydrolyzes bilirubin glucuronides and increases the amount of unconjugated bilirubin

Lipoprotein functions

- Composed of varying proportions of cholesterol, TGs, and phospholipids - LDL and HDL carry the most cholesterol - LDL transports cholesterol from liver to tissue - HDL transports cholesterol from periphery to liver

Dysplastic nevus - What is it? What does it increase a pt's risk for? What is the mutation in dysplastic nevus syndrome?

- Compound nevus that demonstrates architectural and cytologic atypia on histo - Histo features: nests of nevomelanocytes with angulated, hyperchromatic nuclei and bridging nests in neighboring rete pegs - Increased risk for melanoma - Dysplastic nevus syndrome: associated with melanoma susceptibility locus designated CDKN2A on chromosome 9p21 - encodes cyclin-dependent kinase inhibitor 2A, which negatively regulates cell cycle progression at the checkpoint between G1 and S by binding to and inhibiting the cyclin-dependent kinase CDK4 - p16 mutations interfere with its inhibition of CDK4 allowing the cell to inappropriately advance in the cell cycle

Pica

- Compulsive consumption of a nonfood and/or non-staple food source for at least 1 month - most commonly in pregnant women and schoolchildren - Ingested substance is not a culturally accepted food source and consumption is not appropriate to the person's developmental level - 3 main substances consumed: earth/soil-rich substances, raw starch such as flour or cornstarch, and ice

Alkaptonuria

- Congenital def of homogentisate oxidase (homogentisic acid dioxygenase) in the degradative pathway of tyrosine to fumarate --> pigment-forming homogentisic acid accumulates in tissues - Can't metabolize homogentisic acid --> maleylacetoacetate - AR; usually benign - Benign childhood disorder that is marked by severe arthritis in adult life - Findings: bluish-black connective tissue and sclera, urine turns black to prolonged air exposure (due to oxidization of homogentisic acid), may have debilitating arthralgias (homogentisic acid is toxic to cartilage)

Williams syndrome

- Congenital microdeletion of long arm of Ch 7 (deletion region includes elastin gene) - Distinctive "elfin" face, ID, hypercalcemia (increased sensitivity to Vit D), well-developed verbal skills, extreme friendliness with strnagers, CV probs

Cri-du-chat syndrome

- Congenital microdeletion of short arm of Ch 5 - Microcephaly, moderate to severe ID, high-pitched crying/mewing, epicanthal folds, cardiac abnormalities (VSD)

Dystrophin

- Connects the intracellular cytoskeleton (actin) to the transmembrane proteins alpha- and beta-dystroglycan, which are connected to the extracellular matrix - Loss of dystrophin results in myonecrosis

Medulla of the lymph node

- Consists of medullary cords (closely packed lymphocytes and plasma cells) and medullary sinuses - Medullary sinuses communicate with efferent lymphatics and contain reticular cells and macrophages

Fab region of antibody

- Contains the variable and hypervariable regions and consists of light and heavy chains; recognizes antigen - Antigen binding - Determines idiotype: unique antigen-binding pocket; only 1 antigenic specificity expressed per B cell

What are the symptoms of medial pontine syndrome?

- Contralateral spastic hemiparesis (corticospinal tract damage) - Contralateral loss of light touch/vibratory/proprioceptive sensation (medial lemniscus damage) - Ipsilateral internuclear opthalmoplegia (damage to MLF) - Gaze away from side of lesion (damage to pontine gaze center: PPRF) - Ipsilateral paralysis of lateral rectus muscle (damage to abducens nucleus) - Note that pain and temp are preserved

What are the symptoms of medial medullary syndrome?

- Contralateral spastic hemiparesis (pyramid/corticospinal tract damage) - Contralateral tactile and kinesthetic defects (medial lemniscus damage) - Tongue deviates to the side of the lesion (hypoglossal nucleus/nerve damage) - Pain and temp are generally preserved

Function of Vit B6

- Converted to pyridoxal phosphate (PLP), a cofactor used in transamination (eg. ALT and AST) decarboxylation reactions, glycogen phosphorylase. - Synthesis of cystathionine, heme, niacin, histamine, and neurotransmitters including serotonin, epinephrine, norepi, dopamine, and GABA

Phenylethanolamine-N-methyltransferase (PNMT)

- Converts norepinephrine --> epinephrine - Upregulated in the adrenal medulla by cortisol

Vit B6 Def

- Convulsions, hyperirritability, peripheral neuropathy (deficiency inducible by isoniazid-used to tx TB and oral contraceptives), sideroblastic anemias due to impaired hemoglobin and iron excess

What is derived from the fourth and sixth pharyngeal arch?

- Cricoid cartilage, thyroid cartilage, cartilage of larynx - Cricothyroid m, pharyngeal mm (swallow), rest of laryngeal m (speech) - Vagus n, superior laryngeal n, recurrent laryngeal n

What cyclins/CDKs are required for the transition from G2 to M phase of the cell cycle?

- Cyclin A/CDK2 --> mitotic prophase - Cyclin B/CDK1 is activated by cdc25 and leads to the breakdown of nuclear lamins and initiation of mitosis

What cyclins/CDKs are required for transition from G1 to S phase of the cell cycle?

- Cyclin D/CDK4: phosphorylates Rb which is then released from transcription factor EF2 which is then free to transcribe/synthesize components needed for the transition - Cyclin E/CDK2: allows the cell to progress

What is the med tx for serotonin syndrome?

- Cyproheptadine: first generation histamine antagonist with nonspecific 5-HT1 and 5-HT2 receptor antagonist properties - As well as other serotonin antagonists

Topoisomerase II

- DNA Gyrase - During prokaryotic DNA replication, this relieves the tension created during DNA strand unwinding by introducing negative supercoils into the DNA

How is deamination of DNA bases repaired? What causes it?

- Deamination: Conversion of cytosine to uracil or adenine to hypoxanthine - can occur spontaneously or secondary to chemical exposure - Base excision repair: Abnormal bases are recognized and removed by specific glycosylases without disruption of the phosphodiester backbone. The apurinic and apyrimidinic residues are then removed by specific endonucleases and replaced with the correct base by DNA polymerase

What are the 2 extrinsic pathways of apoptosis?

- Death receptor: TNF receptor and Fas receptor are located on the cell membrane; TNF-alpha and Fas ligand activate with receptors; Activated receptors will lead to activation of caspases - Cytotoxic T lymphocyte pathway: Cytotoxic T cells recognize foreign or infected cells; CTLs release perforin and granzyme B; Perforin punches holes in membrane; Garnzyme B enters and activates caspases

Dx of Wilson disease

- Decreased Ceruloplasmin and increased urinary copper excretion - Kayser-Fleischer rings - Increased copper content in liver biopsy

What abnormalities are found in the quad screen in a fetus with fetal growth restriction or in placental insufficiency?

- Decreased estriol levels (AFP is normal)

What are the serum markers of metabolic acidosis?

- Decreased serum pH and HCO3-, compensatory decrease in pCO2

Horner Syndrome

- Decreased sympathetic innervation to the face - Ptosis, miosis, anhydrosis - Could be from compression in the lung

Fish oil/omega-3 fatty acids

- Decreases VLDL synthesis and Apo B synthesis - Decreases triglycerides and increases HDL - Side effect: fishy taste

Niacin

- Decreases fatty acid release, decreases VLDL synthesis, decreases HDL clearance - Decreases LDL and increase HDL - Side effects: flushing and pruritus, hepatotoxicity, hyperuricemia and gout

Ezetimibe

- Decreases intestinal cholesterol absorption - Decreases LDL - Increases hepatotoxicity if given with statins

Kussmaul breathing

- Deep and labored breathing pattern often associated with severe metabolic acidosis (DKA)

I cell disease

- Def in mannose phosphorylation - no mannose-6-phosphate tag so lysosomal enzymes do not enter the lysosome (they get secreted out of the cell instead) - Death by age 8 - Corneal clouding, course facies, hepatosplenomegaly, skeletal abnorms, restricted joint movement - May have ID

Common variable immunodeficiency

- Defect in B cell differentiation - Low or absent levels of IgG, IgE, IgM and IgA

X-linked agammaglobulinemia

- Defect in BTK, a tyrosine kinase gene - Severe immunodeficiency that results from inability to form mature B cells - B cells concentrations are low or absent --> decreased immunoglobulin levels - Absence of lymphoid tissue (tonsils) on exam

Essential fructosuria

- Defect in Fructokinase - AR - Benign, asymptomatic condition, since fructose is not trapped in cells - Symptoms: fructose appears in blood and urine

What is the problem in Chediak-Higashi syndrome? What is the presentation? Histo/Lab findings?

- Defect in lysosomal trafficking regulator gene (LYST) - Microtubule dysfunction in phagosome-lysosome fusion - AR - Recurrent infections by staph and strep, partial albinism, peripheral neuropathy, progressive neurodegeneration, infiltrative lymphohistiocytosis - histo: giant granules in granulocytes (neutrophils) and platelets - Pancytopenia, mild coagulation defects

Lesch-Nyhan Syndrome

- Defective purine salvage due to absent HGPRT which converts hypoxanthine to IMP and guanine to GMP --> excess uric acid production and de novo purine synthesis - X-linked recessive - Findings: ID, self-mutilation, aggression, hyperuricemia (orange "sand" in diaper), gout, dystonia - Tx: allopurinol; 2nd line is febuxostat - HGPRT: Hyperuricemia, Gout, Pissed off, Retardation, dysTonia

Fructose Intolerance

- Deficiency in Aldolase B - AR - Fructose-1-phosphate accumulates --> decrease in available phosphate --> inhibition of glycogenolysis and gluconeogenesis - Symptoms: present following consumption of fruit, juice, or honey; hypoglycemia, jaundice, cirrhosis, vomiting - Urine dipstick will be neg (tests for glucose only); reducing sugar may be detected in urine - Tx: decrease intake of both fructose and sucrose (glucose + fructose)

Metachromatic Leukodystrophy

- Deficiency in Arylsulfatase A - CNS accumulation of cerebroside sulfate - Central and peripheral demyelination --> peripheral neuropathy and ataxia

Hunter syndrome

- Deficiency in Iduronate sulfatase - Accumulate heparan sulfate, dermatan sulfate - Mild Hurler + aggressive behavior; no corneal clouding

Hurler syndrome

- Deficiency in alpha-L-iduronidase - Accumulate Heparan sulfate, dermatan sulfate - Developmental delay, garloylism, airway obstruction, corneal clouding, hepatosplenomegaly

Galactokinase def

- Deficiency of galactokinase - Galactitol accumulates if galactose is present in diet - AR; relatively mild condition - Symptoms: develop when infant begins feeding (due to lactose consumption); galactose appears in blood and urine, infantile cataracts - May present as failure to track objects or to develop a social smile

Hyperimmunoglobulin M Syndrome

- Deficient CD40L-CD40 interaction --> failure of antibody class switching in B cells - X-linked Recessive - Recurrent sinopulmonary and GI infections, infections with opportunistic pathogens, failure to thrive - Increased IgM, decreased IgG, IgA, IgE - Flow cytometry shows absent CD40L on CD4+ T cells

Zinc def

- Delayed wound healing, hypogonadism, decreased adult hair (in axilla, face, and pubic areas), dysgeusia, anosmia, acrodermatitis enteropathica - May predispose to alcoholic cirrhosis

Chylomicron

- Delivers dietary TGs to peripheral tissue; delivers cholesterol to liver in form of chylomicron remnants, which are mostly depleted of their TGs - secreted by intestinal epithelial cells

LDL

- Delivers hepatic cholesterol to the peripheral tissues - FOrmed by hepatic lipase modification of IDL in the liver and peripheral tissue - Taken up by target cells via receptor-mediated endocytosis

Huntington Disease

- Depression, progressive dementia, choreiform movements, and caudate atrophy - Increased dopamine, decreased GABA, decreased ACh CAG repeat on Ch 4 - Demonstrates anticipation

Vit B5 def

- Dermatitis, enteritis, alopecia, adrenal insufficiency

Case Series Study

- Descriptive study that tracks pts with a known condition to document the natural history or response to treatment

IVC filters

- Designs to prevent the propagation of DVT from the legs to the lung vasculature and are used in pts who have contraindication to anticoagulation (such as those with recurrent GI hemorrhages)

What is the tx for von Willebrand disease? How does it help?

- Desmopressin: increases vWF release from epithelial cells - Can also raise factor 8 levels and is used to tx mild hemophilia A

What test is used to diagnose EBV?

- Detecting a heterogenous group of heterophile IgM antibodies that react with antigens on horse erythrocytes - Paul Bunnell test

von Hippel-Lindau disease

- Development of numerous tumors, both benign and malignant - Associated with deletion of VHL gene (tumor suppressor) on Ch 3p

Brain arteriovenous malformations

- Developmental vascular lesions that usually present at age 10-30 - Intracranial hemorrhage, seizure, headache, or focal neurologic deficits

What diseases are associated with HLA-DR3?

- Diabetes Mellitis type 1, SLE, Graves Disease, Hashimoto thyroiditis, Addison disease

What is the murmur heard in mitral stenosis? When is it best heard? What are the symptoms? What is the most common cause of mitral stenosis?

- Diastolic thrill palpable over the cardiac apex and a low-pitched, rumbling, mid-diastolic murmur heard best over the apex when the patient is lying in the left lateral decubitus position - Symptoms: usually asympatomatic; somtimes have symptoms of left heart failure - exertional dyspnea, orthopnea, and paroxysmal nocturnal dyspnea - Most common cause: Rheumatic fever

Allelic heterogeneity

- Different mutations in the same locus can produce the same phenotype - Ex. beta-thalassemia

Right-sided vs Left-sided parietal lobe lesions

- Difficulties with spatial and visual perception - Right-sided: nondominant; hemi-neglect, constructional apraxia and denial of problem - Left-sided: dominant; Gerstmann syndrome - right-left confusion and difficulty with writing and mathematics

How do cardiac glycosides work?

- Digoxin and Digitoxin - Directly inhibit the Na+-K+ ATPase, which indirectly inhibits Na+/Ca2+ exchange --> increased [Ca2+] --> increased cardiac contractility

What explains the HR lowering effects of Digoxin?

- Digoxin slows the ventricular rate during atrial fibrillation primarily by increasing parasympathetic tone which leads to inhibition of AV nodal conduction - Inhibition of the Na-K ATPase pump in vagal afferent finbers sensitizes arterial baroreceptors and cardiac receptors, augmenting afferent input from the cardiovascular system to the brain - Digoxin also enhances efferent parasympathetic ganglionic transmission and potentiated end-organ resopnses to Ach --> increased vagal output

How do the nondihydropyridine Ca2+ channel blockers work?

- Diltiazem and Verapamil - They block the L-type calcium channels --> decrease phase 0 depolarization and conduction velocity in the sinoatrial and AV nodes --> slowing of the sinus rate and conduction through the AV node --> could lead to bradycardia and AV block - Constipation is a major side effect

ATP synthase inhibitors

- Directly inhibit mitochondrial ATP synthase (in the ETC) --> increased proton gradient - no ATP is produced because ETC stops - Oligomycin

Ebstein anomaly

- Displacement of tricuspid valve leaflets downward into the RV --> artificially atrializing the ventricle - Associated with tricuspid regurgitation and right heart failure - Can be caused by lithium exposure in utero

Right-sided vs. Left-sided temporal lobe injury

- Disturbances in language, sensory interpretation, and impaired memory, behavioral changes (hyperorality and hypersexuality - Kluver-Bucy Syndrome) - Right-sided: affects nonverbal memory, including music ability - Left-sided: affects verbal memory, such as word recognition

What is cinchonism? What meds may cause it as a side effect?

- Dizziness, headache, vision changes, tinnitus - Quinidine, Quinine

Bromocriptine

- Dopamine receptor agonist: inhibits pituitary prolactin secretion - Can be used to restore fertility in a woman with hyperprolactinemia

Arnold-Chiari malformation

- Downward displacement of the cerebellar vermis and tonsils below the foramen magnum - Pts frequently have spinal myelomeningocele

Parinaud syndrome

- Due to a pineal gland tumor that damages the dorsal midbrain in the superior colliculus region due to mass effect - Upward gaze palsy, absent pupillary light reflex, impaired convergence

Phenylketonuria

- Due to decreased phenylalanine hydroxylase or tetrahydrobiopterin cofactor (Malignant PKU) - Tyrosine becomes essential - Increased phenylalanine --> excess phenylketones in urine - Tx: decrease phenylalanine and increase tyrosine in diet, tetrahydrobiopterin supplementation - Autosomal recessive - Musty body odor - Must avoid artificial sweetener

Overflow urinary incontinence

- Due to either impaired detrusor contractility or bladder outlet obstruction - Incomplete emptying and persistent involuntary dribbling

Subclavian Steal Syndrome

- Due to hemodynamically significant stenosis of the subclavian artery proximal to the origin of the vertebral a - Subclavian stenosis is typically caused by atherosclerosis, although can also be caused by Takayasu arteritis and complications from heart surgery (aortic coarctation repair) - The lowered distal subclavian arterial pressure leads to reversal in blood flow from the contralateral vertebral artery to the ipsilateral vertebral artery, away from the bloodstream - Presentation: usually asymptomatic; arm ischemia in the affected extremity (exercise-induced fatigue, pain, paresthesias) or vertebrobasilar insufficiency (dizziness, vertigo, drop attacks) - Physical exam: significant difference (>15mmHg) in brachial systolic BP between the affected arm and normal arm - Dx: doppler ultrasound of the cerebrovascular and upper extremity arterial circulation

Why do myocardial cells increase in size after transient myocardial ischemia?

- Due to intracellular Ca2+ accumulation

Lymphedema

- Due to obstruction of the lymphoid capillaries - Marked swelling of the dorsum of the distal limb that may extend proximally - Initially soft and pitting but eventually becomes firm and nonpitting due to progressive fibrosis and thickening of the overlying skin

What are the characteristics of Korsakoff psychosis?

- Due to the chronic effects of thiamine deficiency - Anterograde and retrograde amnesia, apathy, lack of insight, confabulation

Jugular foramen syndrome

- Dysfunction of CNs 9, 10, 11: dysphagia, hoarseness, loss of gag reflex on ipsilateral side, deviation of uvula toward the normal side

What medications are effective in Lyme disease?

- Easily tx with Doxycycline or Penicillin-like antibiotics - If pt does not receive initial tx and goes on to produce facial palsy, Ceftriaxone can be given to prevent the progression into late Lyme disease

What virus causes immortalization of B cells? How?

- Ebola - EBV-encoded oncogenes activate proliferative and anti-apoptotic signaling pathways within the effected B cell. The immortalized B cell is able to secrete immunoglobulins and B-cell activation products (like CD23) with very few of them releasing virus particles at any one time

Nephrotic syndrome

- Effacement of podocytes and loss of negative charge on basement membrane --> proteinuria (>3.5 in urine), loss of antithrombin III, fat deposits, and immunoglobin in the urine --> generalized edema and hypercoaguable state - Thrombosis of renal vein, vericocele

Familial hypercholesterolemia

- Elevated LDL due to defective or absent LDL receptor --> severe atherosclerotic disease early in life, corneal arcus, tendon xanthomas (classically in the achilles tendon) - AD

What type of bacteria are you most susceptible to if you don't have a spleen?

- Encapsulated bacteria: should be vaccinated against Strep Pneumo, H flu, and Neisseria meningitidis

What causes the anion-gap metabolic acidosis in septic shock?

- End organ hypoperfusion in septic shock impairs tissue oxygenation and decreases oxidative phosphorylation --> buildup of NADH and shunting of pyruvate to lactate following glycolysis - Hepatic hypoperfusion during sepsis also contributes to the accumulation of lactic acid as the liver is the primary site of lactate clearance (via conversion back to glucose)

Causes of lactic acidosis

- Enhanced metabolic rate: seizures, exercise - Reduced O2 delivery: Cardiac or pulm failure, tissue ischemia/infarction - Diminished lactate catabolism: hepatic failure or hypoperfusion - Decreased O2 utilization: cyanide poisoning - Enzymatic defects: glycogen storage diseases (con Gierke), mitochondrial myopathies

Sporotrichosis

- Enters body through breaks in skin via thorn prick and spreads via lymphatics - Initial lesion: reddish nodule that later ulcerates that appears at site of prick - Biopsy of lesion: reveals a granuloma consisting of histiocytes, multinucleated giant cells, and neutrophils, surrounded by plasma cells - After spread, forms subcutaneous nosdules and ulcers

What is pathognomic findings for rabies?

- Eosinophilic cytoplasmic inclusions (Negri bodies) in the hippocampal neurons - The Negri bodies consist of nucleocapsid material from the rabies virus

What does the histo look like in Parkinson's disease?

- Eosinophilic inclusions composed of alpha-synuclein filaments (Lewy bodies) are found in the cytoplasm of the remaining neurons - dopaminergic neurons degenerate

How do eosinophils work in parasitic defense?

- Eosinophilic proliferation and activation during parasitic infection is stimulated by IL-5 produced by TH2 and mast cells - When a parasite invades the mucosa or enters the bloodstream, it is coated by IgG and IgE antibodies that bind the Fc receptors located on the eosinophil cell surface --> triggers eosinophil degranulation and release of cytotoxic proteins (such as major basic protein) and reactive oxygen intermediates, substances that damage and destroy antibody-bound parasites - This is an example of ANTIBODY-DEPENDENT CELL-MEDIATED CYTOTOXICITY, which is also used by macrophages, neutrophils, and natural killer cells

What does IF look like in Pemphigous Vulgaris?

- Epidermal, intercellular IgG and C3 deposits in a netlike or "chicken wire" pattern

What is cytokeratin stained to detect?

- Epithelial cells - IDs: Epithelial tumors (squamous cell carcinoma)

What is cytokeratin a component of and what is it stained to identify?

- Epithelial cells: keratin is in desmosomes and hemidesmosomes - Stained to identify carcinoma in epithelial tissue

Lichtenberg figures

- Erythematous cutaneous marks in a fern-leaf pattern usually due to lightening strike

Zinc deficiency

- Erythematous skin lesions (mainly around body orifices) that are vesicular and pustular - Hypogonadism, impaired taste and smell, night blindness, and impaired wound healing

ESR

- Erythrocyte sedimentation rate: how many erythrocytes sediment in one hour - a mark of inflammation if increased

What type of cell/tissue cannot use ketone bodies as energy? Explain.

- Erythrocytes - Ketone bodies are generated in the liver from fatty acids and yield energy when converted to acetyl CoA in the mitochondria of target cells - RBCs do not have mitochondria - The liver is also unable to use ketone bodies for energy because it lacks the enzyme succinyl CoA-acetoacetate CoA transferase, which is required to convert acetoacetate to acetoacetyl CoA

Explain the synthesis and release of estradiol

- Estradiol is the prominent estrogen in the human body - Primarily derived from androgens - synthesized from cholesterol in the theca interna cells - under influence of LH - The androgens then migrate to the granulosa cells, which contain aromatase --> converts the androgens to estradiol - stimulated by FSH

Lithium toxicity

- Etiology: overdose, volume depletion (decreased GFR), Drug interactions (Thiazide diuretics, NSAIDs, ACE inhibitors, Tetracyclines, Metronidazole) - Features: -- Acute: nausea, vomiting, diarrhea, late neurologic sequelae -- Chronic: Confusion, agitation, ataxia, tremors/fasciculations - Tx: hemodialysis for severe cases

Cryptogenic stroke - how is it dx? What is it associated with?

- Evaluated with ACG with a "bubble study": injecting normal saline IV and observing for microbubbles in the left heart - Associated with atrial septal abnorms such as patent foramen ovale and atrial septal defect - 25% of normal appearing adults have a patent foramen ovale

Therapeutic ionizing radiation

- Ex. gamma rays, X-rays - Commonly used to treat or palliate several types of cancer and can cause cell death through 2 major mechanisms: -- DNA double-strand breaks: double breaks are required as single breaks are readily repaired by polymerases -- Free radical formation: Reactive oxygen species are formed by ionization of water; oxygen free radicals are then able to cause cellular and DNA damage - Effect greatest on malignant cells as they are rapidly dividing and consequently less able to repair DNA damage - Epithelial cells are also severely affected because they are rapidly dividing

Recombination

- Exchange of genes between 2 chromosomes via crossing over with homologous regions--> progeny has traits from both parents - Passing of resistance traits between 2 similar viruses is an example

Exons vs Introns

- Exons: actual genetic information coding for a protein - Introns: intervening noncoding segments of DNA

What are the virulence factors of Pseudomonas?

- Exotoxin A: inhibits protein synthesis - Elastase: degrades elastin - important for blood vessel destruction - Phospholipase C: degrades cellular membranes - Pyocyanin: generates reactive oxygen species

When do you hear the S4 heart sound? What is it associated with?

- Extra low frequency heart sounds heard at the end of diastole just before S1 - Often heard in older adults due to an age-related decrease in left ventricular compliance - benign finding - The louder the sound, the more likely it is due to a pathologically stiff ventricle - occurs in restrictive cardiomyopathy and left ventricular hypertrophy following prolonged HTN - S4 in younger pts is always pathologic

Malignant hypertension - What is it? What 2 things does it cause?

- Extreme or rapidly developing hypertension - Fibrinoid necrosis: localized destruction of the vascular wall with a circumferential ring of pink, amorphous material surrounding the lumen - Hyperplastic arteriolosclerosis: onion-like, concentric thickening of the walls of arterioles due to laminated layers of smooth m cells with intervening basement membrane reduplicaiton (onion skinning)

Marfan syndrome mutation

- FBN1 gene mutation on Ch 15 --> defective fibrillin (scaffold for elastin)

Excess Vit B3

- Facial flushing (induced by prostaglandin, NOT histamine, and can be avoided by taking aspirin with niacin), hyperglycemia, hyperuricemia

Second pharyngeal arch

- Facial nerve (CN7) - Styloid process of the temporal bone, lesser horn of the hyoid, and stapes

Mucormycosis

- Facial pain, headache, and nasal eschar (characteristic) in a pt with diabetic ketoacidosis - Caused by Mucor or Rhizopus - The infection is acquired through spore inhalation, ascends from the nasal passage to the sinuses/orbits and then sometimes to the brain --> confusion, neuro defects, and death - Histo: broad ribbon-like nonseptate hyphae with right angle branching - Dx: must be done via mucosal biopsy to see histo - Tx: amphotericin B and surgical debridement

GLUT2

- Facilitates export of glucose from the liver, small intestine, and kidneys into the circulation - Also helps control insulin secretion in the pancreas

Cryptorchidism

- Failure of the fetal testis to descend into the scrotum

Fatty acid metabolism (pic)

- Fatty acid synthesis requires transport of citrate from mitochondria to cytosol; predominately occurs in liver, lactating mammary glands, and adipose tissue - Long chain fatty acid degradation requires carnitine-dependent transport into the mitochondrial matrix

DRESS Syndrome

- Fever, generalized lymphadenopathy, facial edema, and diffuse morbilliform skin rash that can progress to a confluent erythema with follicular accentuation - may also affect liver, kidney, and lung - Presents 2-8 weeks after drug exposure - Associated drugs include anticonvulsants, allopurinol, sulfonamides, and antibiotics - Lab studies: eosinophilia, atypical lymphocytes, and elevated serum alanine transaminase - Symptoms improve after withdrawal from the drug

Primary genital herpes

- Fever, myalgia, inguinal lymphadenopathy, and itchy, painful, vascular genital rash (vesicles --> ulcers --> crusting) - HSV-2 - Lies dormant in the sacral dorsal root ganglia and can be reactivated to cause recurrent genital lesions

What is the most likely adherence site of strep viridans on heart valves?

- Fibrin-platelet aggregates: they are deopsited at sites of endothelial trauma and provide a site for bacterial adherence and colonization during bacteremia - Side note: staph aureus is more aggressive and can adhere to intact valves

Erythema Infectiosum: What causes it? What is the timeline of symptoms? In what type of cell does the causal organism replicate?

- Fifth disease caused by Parvovirus B19 (ssDNA virus) - 1-2 week incubation period, followed by a nonspecific prodrome period (malaise, congestion, headache, fever), and then a erythematous rash on the cheeks, followed by a lacy, reticular rash over the trunk and extremities (probably caused by immune complex deposition) - Parvovirus B19 replicates in erythrocyte precursors in the bone marrow - express blood group P antigen (aka globoside) which is the cell receptor for parvovirus

Hepatic abscess

- Fluid-filled cavity in the liver in conjunction with fevers, chills, and right upper abdominal pain - Underdeveloped countries: usually caused by parasitic infections (Entamoeba histolytica, achinococcal) - Developed countries: rare; usually caused by bact. infection

What is considered the drug of choice to treat Bulemia?

- Fluoxetine (best when combined with nutritional rehab and CBT)

Function of Vit B9 and where is it found?

- Folate - Converted to tetrahydrofolic acid (THF), a coenzyme for 1-carbon transfer/methylation reactions - Important for synthesis of nitrogenous bases in DNA and RNA - Important in pregnancy!! - Found in leafy green veggies, absorbed in jejunum - Small reserve pool stored primarily in the liver

Describe movement of particles through the Na+/K+ pump

- For each ATP consumed, 3Na+ go out of the cell (pump phosphorylated) and 2K+ come into the cells (pump dephosphorylated)

Membranous glomerulonephropathy

- Form of nephrotic syndrome - LM: thickened basement membrane - Caused by auto-Abs against phospholipase A2 on podocytes --> subendothelial Ab deposits - EM: spike and dome appearance - Secondary to solid tumor, viral infection, drug rxn, SLE - IF: granular deposits of Ig and complement along basement membrane - Tx: corticosteroids

Cholesterol gallstones

- Form when the ability of bile salts to solubilize cholesterol is overwhelmed by high concentrations of cholesterol in bile - Yellow-pal gray and hard

IDL

- Formed in the degradation of VLDL - delivers TGs and cholesterol to the liver

alpha-Amanitin

- Found in Amanita phalloides (death cap mushrooms) - Inhibits RNA poly 2 - Causes severe hepatotoxicity

P Bodies

- Found in the cell cytoplasm - Distinct foci within eukaryotic cells that are involved in mRNA regulation and turnover - Play a fundamental role in translation repression and mRNA decay - Contain numerous proteins including RNA exonucleases, mRNA decapping enzymes, and constituents involved in mRNA quality control and microRNA-induced mRNA silencing - Also function as a form of mRNA storage: certain mRNAs are incorporated into P bodies only to be later released and utilized for protein translation

Protein A

- Found in the cell wall of staph aureus - helps prevent opsonization by binding the Fc region of immunoglobulins

M protein

- Found on the cell wall of Strep species - Binds factor H to prevent opsonization and destruction of streptococci by the alternative complement pathway

Para-aminohippuric acid (PAH) - where is concentration the lowest?

- Freely filtered by the glomerulus into the Bowman's space, but the majority is secreted by the proximal tubule via carrier-mediated active transport - Not reabsorbed - Lowest PAH concentration is in the Bowman's space (similar to that in the plasma)

Lung adenocarcinoma

- Frequently affects smokers and can present with cough, hemoptysis, and pulmonary consolidation with air bronchograms - Histo: cuboidal to low columnar hyperchromatic cells with pleomorphism, prominent nucleoli, and intracellular mucin

Metabolism of non-glucose monosaccharides (pic)

- Fructose: bypasses phosphofructokinase (the major rate-limiting enzyme in glycolysis) --> metabolized by the liver faster than the other monosaccharides and is rapidly cleared from the bloodstream following dietary absorption

Mucor

- Fungus usually found in soil and decaying material - Mucormycosis: results when the fungus in inhaled, causing sinopulmonary and sometimes angioinvasive disease, often in pts with DKA - Histo: broad, ribbon-like, nonseptate hyphae with right-angle branching

Krabbe Disease

- Galactocerebrosidase deficiency - Accumulation of galactocerebroside and psychosine - Infants may have developmental delay and/or regression, hypotonia, optic atrophy, and seizures

Other than alkaline phosphatase, what can be measured to check liver/biliary function?

- Gamma-glutamyl transferase

What does DNA polymerase I do in prokaryotes that DNA poly III doesn't? What can they both do?

- Generally they do the same thing - 5' --> 3' DNA synthesis and 3' --> 5' exonuclease ("proofreading") activity - DNA poly I: also removes RNA primer (5'-->3' exonuclease activity) and replaces it with DNA

Treacher-Collins syndrome

- Genetic disorder resulting in the abnormal development of the first and second pharyngeal arches - The craniofacial abnormalities (mandibular, maxillary, and zygomatic bone hypoplasia) --> airway compromise and feeding difficulties - Absent or abnormal ossicles (incus, malleus, stapes) --> profound conductive hearing loss - Associated with neural crest dysfunction

Nephritic syndrome

- Glomerular damage due to immune complex deposition --> IF shows granular pattern due to IC and complement deposition - low C3 in serum - Hematuria (tea, cola-colored urine), RBC and WBC casts, less proteinuria than nephrotic syndrome - Decreased GFR: decreased urine output, increased BUN, HTN, edema (mild/periorbital - not generalized as in nephrotic syndrome)

Vit B3 def

- Glossitis - Severe def can lead to pallegra, which might be caused by Hartnup Disease, malignant carcinoid syndrome (increased tryptophan metabolism), and isoniazid (decreases Vit B6)

G6PD def presents the same as a deficiency in what other enzyme?

- Glutathione reductase

What are the 2 major processes that maintain plasma glucose levels between meals?

- Glycogenolysis: primary source of glucose for the first 12-18 hours of fasting - Gluconeogenesis: Major process once hepatic glycogen stores have been depleted

What fuels body in the fed state?

- Glycolysis and aerobic respiration - Insulin stimulates storage of lipids, proteins, and glycogen

What causes bulging eyes and eye grittiness in Grave's disease?

- Glycosaminoglycan synthesis by fibroblasts

What post-translational modifications occurs in the Golgi Apparatus?

- Glycosylation of core proteins to form proteoglycans - Sulfation of proteoglycans and selected tyrosine residues - Add O-oligosaccharides to serine and threonine - Adds mannose-6-phosphate to asparagine residues located on lysosomal enzymes and tags them to be sent to the lysosome

Chronic renal allograft rejection

- Gradual deterioration in graft function that occurs at least 3 months post-transplant in the absence of other precipitating events - Features: worsening hypertension, progressive rise in serum creatinine, proteinuria with normal urinary sediment - Begins with graft endothelial damage mediated by low-grade cellular and humoral immune responses directed against alloantigens --> obliterative fibrous intimal thickening and scattered mononuclear infiltration of the surrounding tissues - Renal ischemia and chronic inflammation cause shrinking of the renal parenchyma with tubular atrophy and interstitial fibrosis

Actinomyces

- Gram + anaerobic bacteria - Typically colonize mouth, colon, and vagina and can be found in dental caries as well as margins of gums in those with porr dental hygiene - Infection --> cervicofacial abscesses but systemic infection may develop anywhere in the body when the mucosa is disrupted

Allergic Asthma

- Granule containing cells seen in sputum are usually eosinophils and the crystalloid bodies are Charcot-Leyden crystals (contain eosinophil membrane protein) - Largely due to IL-5 released by allergen-activated Th2 cells

What are the side effects of statins? How do they work and what are they used for?

- HMG-CoA reductase inhibitors are the first line tx for pts with hypercholesterolemia --> reduce risk of cardiac events - Myopathy and hepatitis - **Perform liver function tests before beginning statin therapy**

Where and when is a wide split S2 heart sound heard? What causes this sound?

- Heard at the upper sternal border - Occurs due to lengthening of right ventricular ejection time with delayed closure of the pulmonary valve - may be heard with complete right bundle branch block, pulmonary stenosis, and pulmonary arterial hypertension

What is the main function of brown fat in babies? How is it different than white fat found in adults?

- Heat production - if fat is removed, it could lead to hypothermia - Possesses several small intracytoplasmic fat vacuoles and considerably more mitochondria than white fat seen in adults - also has higher O2 requirement and contains more capillaries than white fat

Regulatory T cells

- Help maintain specific immune tolerance by suppressing CD4 and CD8 T-cell effector functions - Identified by expression of CD3, CD4, CD25, and FOXP3 - Activated regulatory T cells produce anti-inflammatory cytokines (such as IL-10, TGF-beta)

What does hemaglutinin on the Influenza virus do? Neuroaminidase?

- Hemaglutinin: promotes viral entry into cells - Neuroaminidase: promotes progeny virion release from infected cells

What is Polycythemia (erythrocytosis) and what tests can be used to help determine the cause?

- Hematocrit > 52% in men and >48% in women - may be result of true increase in RBC mass (absolute) or decrease in plasma volume (relative) - Tests: -- Absolute vs. Relative: direct measurement of RBC mass is needed - an increase in RBC mass = absolute; if no increase in mass = relative due to aggressive diuretic therapy for CHF exacerbation -- Primary vs. Secondary: Primary is associated with low erythropoietin levels and is caused by myeloproliferative disorders such as polycythemia vera; secondary is characterized by increased erythropoietin levels due to chronic hypoxia from high altitudes, smoking, or COPD -- Hypoxic vs. other secondary causes: measurement of arterial O2 saturation is important to exclude hypoxemia - if SaO2 <92% (PaO2 <65mmHg) --> secondary polycythemia due to hypoxemia

What disease is HLA-A3 associated with?

- Hemochromatosis

Vit E Def

- Hemolytic anemia, acanthocytosis, mm weakness, posterior column and spinocerebellar tract demyelination - Neuro symptoms may resemble those of B12 def, but without megaloblastic anemia, hypersegmented PMNs, or increased methylmalonic acid levels

What fuels body in the fasting state (between meals)?

- Hepatic glycogenolysis (major), hepatic gluconeogenesis, adipose release of FFA (minor) - Glucagon and epinephrine stimulate use of feul reserves

How are blood glucose levels maintained in starvation state from days 1-3?

- Hepatic glycogenolysis, adipose release of FFA, muscle and liver which shift fuel use from glucose to FFA, Hepatic gluconeogenesis from peripheral tissue lactate and alanine, and from adipose tissue glycerol and propionyl-CoA (from odd-chain FFA - the only triglyceride components that contribute to gluconeogenesis) - glycogen reserves depleted after day 1 - RBCs lack mitochondria and therefore cannot use ketones

Kupffer cells

- Hepatic macrophages that line the walls of sinusoids and participate in RBC breakdown - May see hemosiderin in these cells - seen with Prussian-blue stain

Clinical findings of Wilson disease

- Hepatic: acute liver failure, chronic hepatitis, cirrhosis - Neurologic: parkinsonism, gait disturbance, dysarthria - Psychiatric: depression, personality changes

Cystinuria

- Hereditary defect of renal PCT and intestinal amino acid transporter that prevents reabsorption of Cystine, Ornithine, Lysine, and Arginine (COLA) - Excess cystine in urine can lead to recurrent precipitation of hexagonal cystine stones - AR - Dx: urinary cyanide-nitroprusside test - Tx: Urinary alkalinization (ex. potassium citrate, acetazolamide), and chelating agents (penicillamine) increase solubility of cystine stones, good hydration

Lynch syndrome

- Hereditary nonpolyposis colon cancer - AD - Defective DNA mismatch repair - typically due to mutations of the MSH2 and MLH1 genes, which code for components of the human MutS and MutL homologs

What would be the ABG findings in Heroin overdose?

- Heroin overdose is an acute event and it suppresses respiratory centers and causes hypoventilation with retention of CO2 - Uncompensated respiratory acidosis: low pH, high CO2, normal bicarb

What are the TSH, T3 and T4 levels in Hashimoto's Thyroiditis?

- High TSH - Low T4 - Normal T3 - T4 is the hormone that is released directly from the thyroid - T3 is the more active form the is produced primarily by deiodination of T4 in the peripheral tissues - T3 has a short half-life and conversion in the peripheral tissues can be variable and T3 levels may fluctuate significantly --> usually remain normal until late stage thyroiditis

What properties are present in drugs that are primarily metabolized by the liver?

- High lipophilicity, high volume of distribution

What can be used for acute tx of delirium?

- High-potency first-generation antipsychotics (such as Haloperidol) and some second-generation antipsychotics can be used to tx the agitation and psychosis associated with delirium - The best tx for delirium overall is to tx the underlying cause (UTI, etc)

Heterochromatin

- Highly condensed DNA that is statically inaccessible and is transcriptionally inactive - Barr bodies inactive X chromosomes that are heterochromatin

What is increased in the urine of pts with Alkaptonuria? What are the signs of alkaptonuria?

- Homogentisic acid levels - turns urine black - Will also see blue-black pigment deposition in eyes, ears and nose as well as ochronotic osteoarthropathy (pigment deposition in the spine and large joints)

Cholecystokinin

- Hormone responsible for gallbladder contraction - Produced by the I cells of the duodenum and jejunum when fat-protein-rich chyme enters the duodenum - Functions: increase pancreatic enzyme secretion (by acinar cells) and gallbladder contraction, decrease gastric emptying

Paracortex of the lymph node

- Houses T cells - Region of cortex between the follicles and the medulla - Contains high endothelial venules through which T and B cells enter from blood - Not well developed in pts with DiGeorge syndrome - Enlarges in an extreme cellular immune response (viral infection)

What do you see on histo after a splenectomy?

- Howell-Jolly bodies (nuclear remnants) - pic - Target cells - Thrombocytosis (loss of sequestration and removal) - Lymphocytosis (loss of sequestration)

What is Menotropin? It's use mimics what physiological effect?

- Human menopausal gonadotropin - Mimics FSH: triggers the formation of a dominant ovarian follicle - Used in infertile women - hCG can the be given to induce ovulation

Collagen synthesis

- Hydroxylation of the proline and lysine residues are required for appropriate triple helix formation

What drug inhibits both purine and pyrimidine synthesis? How?

- Hydroxyurea: inhibits ribonucleotide reductase

CD40 ligand deficiency

- Hyper IgM-syndrome - Inability of T cells to activate B cell immunoglobulin class switching - only IgM is produced - Serum: markedly elevated IgM levels and low or absent levels of other Igs

Job syndrome

- Hyper-IgE syndrome - Causes recurrent skin and lung infections - High levels of IgE with all others normal - Deficiency of Th17 cells due to STAT3 mutation --> impaired recruitment of neutrophils to sites of infection - "FATED": coarse Facies, cold staph Abscesses, retained primary Teeth, increased IgE, Derm probs (eczema)

Homocystinuria

- Hypercoagulability and thromboembolic occlusion; premature acute coronary syndrome - Other clinical features: ectopia lentis and ID - Usually a defect in cystathionine synthase: pts cannot form cysteine from homocysteine --> cysteine becomes essential - Homocysteine buildup --> hypermethioninemia

Gastrinoma

- Hypersecretion of gastric acid and resultant gastrointestinal ulceration - Peptic ulcers are in unusual areas - such as the jejunum - May have diarrhea and abdominal pain

Characteristics of legionella (chart)

- Hyponatremia is the most common lab abnormality

What results when the urethral folds do not fully fuse in males?

- Hypospadias

What is the disease when you have hemoptysis, hypertension, and hematuria with a picture of IF of neutrophils? Explain.

- IF of neutrophils: c-ANCA - an autoantibody reaction directed against lysosomal enzymes of human neutrophils and macrophages - If c-ANCA present: granulomatosis with polyangiitis (Wegener's) - Usual symptoms include hemoptysis, chronic sinusitis or mucosal ulceration of the nasopharynx from the development of mucosal granulomas that later ulcerate, and RPGN (hematuria)

What cytokines enhance the activity of natural killer cells?

- IL-2, IL-12, IFN-alpha, IFN-beta

What method is used to achieve fertility in a pt with Turner's syndrome? What should be tested before this is carried out? What problems might arise if pt gets pregnant on her own?

- IVF: usually pts with Turner's syndrome are infertile due to ovarian failure - with estrogen and progesterone supplements they can develop a thick endometrial lining that is substantial enough to support pregnancy - A thorough renal, cardiac, and thyroid examination should be carried out before pregnancy is attempted to reduce potential for complications - If pregnancy occurs spontaneously: pts are at risk for spontaneous abortion, Down syndrome, and Turner syndrome

Causes of restrictive cardiomyopathy

- Idiopathic, infiltrative diseases (amyloidosis, sarcoidosis, hemochromatosis) - associated with ventricular hypertrophy, radiation fibrosis, or and myocardial fibrosis

Loss of heterozygosity

- If a pt inherits a mutation in a tumor suppressor gene, the complementary allele must be deleted/mutated before cancer develops - not true of oncogenes - Ex: Retinoblastoma and the "two-hit hypothesis", Lynch syndrome, Li-Fraumeni syndrome

What are 6 types/causes of nephritic syndrome?

- IgA nephropathy, post-strep glomerulonephritis, diffuse proliferative glomerulonephritis, membranoproliferative glomerulonephritis, dense deposit disease, rapidly progressive glomerulonephritis

What do mature naive B cells prior to activation express on their surfaces?

- IgM and IgD

What is the most specific marker for dx of acute Hep B?

- IgM anti-HBc - present in the window period and is present when HBsAg is clears and anti-HBs is not yet detectable - IgG signals the recovery from the disease - is detectable for life

Meckel Diverticulum

- Ileal outgrowth from failed obliteration of the vitelline (omphalomesenteric) duct - If symptomatic: spontaneous but painless lower GI bleeding - May lead to intussusception - colicky abdominal pain and currant jelly stools - Ectopic gastric mucosa in the meckel diverticulum secretes acid and causes local ulceration and bleeding - Radioisotope 99mTc-pertechnetate has an affinity for pariental cells of the gastric mucosa (including ectopic sites) - increased uptake in the periumbilical/right lower quadrant is characteristic of Meckel diverticulum

What specifically is defective in Kartagener syndrome?

- Immotile cilia due to dynein arm defect - Increases risk of ectopic pregnancy, can cause bronchiectasis, recurrent sinusitis and situs inversus

Vitamin B1 deficiency

- Impaired glucose breakdown --> ATP deletion worsened by glucose infusion - Highly aerobic tissues are affected first: brain and heart - Wernicke-Korsakoff and Beriberi are seen in malnutrition and alcoholism - Dx: increase in RBC transketolase activity following Vit B1 administration - Def --> increased serum lactate and decreased pH as pyruvate is shunted to lactate

What can mutations involving Fas or FasL lead to?

- Impairs the process of T-lymphocyte activation-stimulated cell death --> accumulation of autoreactive T-cells and the development of autoimmune diseases, such as SLE

Truncus arteriosus

- Incomplete development of the aorticopulmonary septum - Causes cyanosis in newborns and required early surgical repair

What are the 3 mechanisms by which the kidneys try to correct metabolic acidosis in DKA?

- Increase HCO3- reabsorption - Increase H+ secretion: proximal nephron and in the alpha-intercalated cells of the distal tubular segment - Increased acid buffer excretion: the two most important buffers in the urine are HPO42- and NH3

What changes in amniotic fluid are associated with neural tube defects?

- Increased acetylcholinesterase levels - Open neural tube defects: increased alpha-fetoprotein

Findings of homocysteinuria

- Increased homocysteine in urine, ID, osteoporosis, marfanoid habitus, kyphosis, lens sublexation (downward and inward), thrombosis, and atherosclerosis (stroke and MI)

Open-angle glaucoma

- Increased intraocular pressure due to increased secretion or decreased outflow of aqueous humor - Causes progressive loss of ganglion cell axons, which may be visualized as a pale optic disc and enlarged optic cup - Progressive loss of peripheral visual fields

What is a characteristic test of Meckel diverticulum?

- Increased uptake of 99mTc-pertechnetate in the RLQ - this is a sign of ectopic parietal cells (gastric mucosa) in this area

What defects are associated with increased maternal serum AFP? Decreased AFP?

- Increased: open neural tube defects, ventral wall defects (omphalocele, gastroschisis), multiple gestation - Decreased: aneuploidies (trisomy 18 & 21)

How does chronic anemia affect cardiac output and venous return?

- Increases cardiac output in an effort to meet the metabolic demands of the tissues - Venous return is somewhat increased due to decreased blood viscosity

Vit D function

- Increases intestinal absorption of calcium and phosphate, increases bone mineralization at low levels, increases bone resorption at higher levels

Uncoupling agents (in the ETC)

- Increases permeability if membrane --> a decreased proton gradient and increased O2 consumption - ATP synthesis stops but ETC continues --> produces heat - 2,4-Dinitrophenol, aspirin (fever occurs after aspirin OD), thermogenin in brown fat

What does ethanol metabolism do to the NADH/NAD+ ratio? What effect does that cause?

- Increases the ratio in the liver - Pyruvate --> lactate (lactic acidosis) - Oxaloacetate --> malate (prevents gluconeogenesis --> fasting hypoglycemia) - Dihydroxyacetone phosphate --> glycerol-3-phosphate (combines with fatty acids to make triglycerides --> hepatosteatosis) - Disfavors TCA production of NADH --> increased utilization of acetyl-CoA for ketogenesis (--> ketoacidosis) and lipogenesis (--> hepatosteatosis)

Indirect vs Direct hernias

- Indirect: tend to appear on the right side; occur due to failure of the processus vaginalis to obliterate, allowing abdominal contents to protrude through the deep inguinal ring - abdominal contents follow the path of the inguinal canal and may exit through the external inguinal ring - Direct: protrude through Hesselbach's triangle, a weak spot in the anterior abdominal wall - less prone to incarceration due to their wide neck, and do not descend into the scrotum - Hesselbach's triangle: bounded by the rectus abdominis m medially, inferior epigastric vessels laterally, and inguinal ligament inferiorly

How does the inactivated Influenza vaccine work?

- Induces neutralizing Abs against the hemagglutinin antigen in selected viral strains - upon viral exposure through natural infection, these Abs inhibit binding of hemagglutinin to sialylated receptors on the host cell membrane --> prevents the live virus from entering cells via endocytosis

Fat necrosis of the breast

- Inflammatory response to trauma (seatbelt injury) or invasive breast procedures - Presentation: irregular, firm mass that may be accompanied by ecchymosis (bleeding under skin)

Systemic primary carnitine deficiency

- Inherited defect in transport of long chain fatty acids into the mitochondria --> toxic accumulation - Weakness, hypotonia, and hypoketotic hypoglycemia

ETC inhibitors

- Inhibit ETC --> decreased proton gradient and block of ATP synthesis - Rotenone: complex 1 inhibitor - Antimycin: complex 3 inhibitor - CO/CN: complex 4 inhibitors

Disulfiram

- Inhibits acetaldehyde dehydrogenase (acetaldehyde accumulates --> hangover symptoms)

Probenecid

- Inhibits organic anion transporters in the kidney - may give with Penicillin to increase serum Penicillin concentrations - May also increase uric acid excretion (helpful in gout pts)

Pudendal nerve injury

- Innervates the external urethral and anal sphincters - Injury: fecal incontinence, decreased penile sensation, or external urethral sphincter paralysis

GLUT4

- Insulin-sensitive glucose transporter found in skeletal muscle cells and adipocytes - The GLUT4 protein is stored in cytoplasmic vesicles - under the influence of insulin, the transporter protein is incorporated into the cell membrane --> glucose uptake by the cells

Orlistat

- Intestinal lipase inhibitor that reduces absorption of dietary fat - first-line medication due to favorable safety profile - GI side effects: diarrhea, fecal incontinence, oily spotting

What are the symptoms of lateral inferior pontine syndrome?

- Ipsilateral facial nerve paralysis (facial nucleus and nerve fiber damage) - Ipsilateral limb and gait ataxia (damage to middle cerebellar peduncle) - Ipsilateral loss of pain and temp sensation from the face (spinal trigeminal nucleus and nerve fiber damage) - Contralateral loss of pain and temp sensation (damage to the spinothalamic tract) - Ipsilateral Horner syndrome (damage to the descending sympathetic tract) - No contralateral body paralysis or loss of light touch/vibratory/proprioceptive sensation

Pontine hemorrhages - signs

- Ipsilateral facial weakness or sensory loss, ataxia, gaze paresis, miosis, decreased consciousness - Strength in extremities is usually preserved and limb posturing is not observed

What kind of vaccine is the tetanus vaccine? How does it work?

- It is a tetanus toxoid vaccination (formaldehyde-inactivated toxin) - Elicits humoral immunity specific for the tetanus toxin

What is lactulose used to tx?

- It is an osmotic laxative that can be used to treat constipation - It can also tx hepatic encephalopathy since gut flora degrade it into metabolites (lactic acid and acetic acid) that promote nitrogen excretion (NH4+)

What is desmin a component of and what is it stained to identify?

- It is in all types of mm cells - Stained to identify Rhabdomyosarcoma and leiomyosarcoma

Why is early penicillin treatment of Group A strep pharyngitis important?

- It prevents acute rheumatic fever - Does not affect the occurrence of Post-strep glomerulonephritis

Xerosis

- Itchy rash and dry, cracked skin, usually in the winter ("winter itch") - most common in elderly pts

Classical type of Ehlers-Danlos syndrome

- Joint and skin symptoms - Due to mutation in type V collagen

Alport syndrome

- Kidney disease (nephritis) + deafness + eye probs (cataracts) - Defect of type 4 collagen

Cytotoxic T cells

- Kill virus-infected, neoplastic, and donor graft cells by inducing apoptosis - Release cytotoxic granules containing preformed proteins (perforin, granzyme B) - Have CD8, which binds MHC I on virus-infected cells

The use of hCG therapy in infertile women primarily mimics what physiologic event?

- LH surge: causes the rupture of the dominant follicle --> ovulation

What does LM look like for shingles? Skin biopsy?

- LM: Intranuclear inclusions in keratinocytes and multinucleated giant cells (positive Tzanck smear) - Skin biopsy: acantholysis (loss of intercellular connections) of keratinocytes and intraepidermal vesicles

Maternal PKU

- Lack of proper dietary therapy during pregnancy - Findings in infant: microcephaly, ID, growth retardation, congenital heart defects

Lactase deficiency

- Lactose intolerance - Lactase functions at the brush border to digest lactose --> glucose and galactose - Primary: age-dependent decline after childhood (absence of lactase-persistent allele), common in people of Asian, African, or Native American descent - Secondary: loss of brush border due to gastroenteritis (rotavirus), autoimmune disease, etc. - Congenital: rare; due to defective gene - Stool demonstrates decreased pH and breath shows increased hydrogen content with lactose hydrogen breath test - Intestinal biopsy: normal mucosa in pts with hereditary lactose intolerance

What is a symptom of occlusion of the Posterior Cerebral Artery (PCA)?

- Leads to ischemic injury to the ipsilateral striate cortex --> contralateral homonymous hemianopia with macular sparing -- Macula is supplied by the MCA

What ratio in the amniotic fluid is used to measure fetal lung maturity?

- Lecithin (Phosphatidylcholine)/Sphingomyelin ratio - In the third trimester, the fetal lungs begin to make surfactant - the [lecithin] increases while sphingomyelin remains the same - by 35 weeks the ratio is 2:1 or higher

What are 3 meds that affect pyrimidine synthesis? What effect does each have?

- Leflunomide: inhibits dihydroorotate dehydrogenase - Methotrexate, Trimethoprim, Pyrimethamine: inhibit dihydrofoloate reductase (decreases dTMP) in humans, bacteria, and protozoa respectively - 5-fluorouracil: forms 5-f-dUMP, which inhibits thymidylate synthase (decreases dTMP)

What causes a left shift in the oxygen-hemoglobin dissociation curve? What does this mean? Right shift?

- Left shift: Hb has a higher affinity for O2 - fetal Hb, Decreased H+ (alkalotic), decreased 2,3-BPG, decreased temp - Right shift: Increased H+ (acidotic), increased 2,3-BPG, increased temp

Occlusion of what artery would lead to the retrograde (caudal) flow of blood through the left vertebral artery instead of normal antegrade flow?

- Left subclavian A

Left-sided vs right-sided frontal lobe lesions

- Left-sided: associated with apathy and depression - right sided: associated with disinhibition behavior

Gerstmann syndrome

- Lesion of the dominant angular gyrus (usually left parietal lobe) - posterior and superior to Wernicke's area - Agraphia, acalculia, finger agnosia

Hemispatial neglect syndrome

- Lesion of the nondominant angular gyrus

Euchromatin

- Less condensed, transcriptionally active

What mm are you exercising when doing Kegel exercises? What happens when these mm are injured?

- Levator ani mm: iliococcygeus m, pubococcygeus m, puborectalis m; which hold the bladder and the urethra in the appropriate anatomic position - Injury to these mm --> urethral hypermobility and/or pelvic organ prolapse --> stress urinary incontinence

What syndrome is associated with an inherited mutation in p53?

- Li-Fraumeni syndrome: autosomal dominant cancer syndrome

What nerve mediates the cremaster reflex?

- Lightly stroking the medial thigh causes contraction of the cremaster mm to pull up the ipsilateral testis - Mediated by the genitofemoral n: originates from the L1-L2 spinal nn - Loss of this reflex is commonly seen with testicular torsion or L1-L2 spinal injury

What type of vaccines elicit a cell-mediated immune response?

- Live attenuated vaccines: strongly stimulate the MHC class I antigen-processing pathway and can generate cytotoxic CD8+ T cells that kill infected cells - Inactivated viral vaccines do not infect host cells and therefore do not enter the MHC class I antigen-processing pathway

Where does copper accumulate in Wilson's disease?

- Liver, brain, kidney, and Descemet's membrane of the cornea of the eye - Kayser-Fleischer rings - Presentation: at age 30s-40s with hepatitis, splenomegaly, an hemolytic anemia - Neuro signs: dystonia, tremor, dysarthria, dysphagia - May also have behavioral changes

Suprapatellar bursitis

- Located anteriorly between the distal femur and quadriceps - Most often caused by a direct blow to the distal thigh or prolonged/repetitive quadrideps activity (running)

Subdural hemotoma

- Located between dura mater and arachnoid mater - Damage to the Bridging Cortical Vv - Symptoms: gradual onset of headache and confusion - Crescent shaped

Subarachnoid hemorrhage

- Located between the arachnoid and pia mater - Due to aneurysm or AV malformation of anterior and posterior communicating arteries - Symptoms: severe headache ("the worst headache of my life"), fever, nuchal rigidity - On CT: blood in the basal cisterns

Anterior nucleus of the hypothalamus

- Located in anterior hypothalamus - Thermoregulation (cooling) - Damage causes hyperthermia

Mammillary bodies

- Located in posterior hypothalamus - Important in memory - Damage causes Wernicke-Korsacoff syndrome

Arcuate nucleus of the hypothalamus

- Located in the Tuberal hypothalamus - Secretes GHRH, dopamine, pulsatile GnRH secretion (important for normal ovulation) - Regulates appetite

Suprachiasmic nucleus

- Located in the anterior hypothalamus - Circadian rhythms - gets input from the retina

Preoptic nucleus

- Located in the anterior hypothalamus - Secretes GnRH (--> LH, FSH)

Paraventricular nucleus

- Located in the anterior hypothalamus - Secretes Oxytocin (posterior pit), CRH and TRH

Supraoptic Nucleus

- Located in the anterior hypothalamus - Used for H2O balance - Secretes ADH (from the posterior pit) - Damage causes central DI --> can't concentrate your pee

Thymus

- Located in the anterosuperior mediastinum - Site of T cell differentiation and maturation - Derived from 3rd pharyngeal arch - Lymphocytes of mesenchymal origin - Cortex: dense with immature T cells - Medulla: pale with mature T cells and Hassall corpuscles containing reticular cells

Posterior nucleus of the hypothalamus

- Located in the posterior hypothalamus - Thermoregulation (warming) - shivering, piloerection - Damage causes hypothermia

Lateral nucleus of the hypothalamus

- Located in the tuberal hypothalamus - Regulates hunger - Inhibited by Leptin - Damage leads to anorexia and weight loss

Ventromedial nucleus of the hypothalamus

- Located in the tuberal hypothalamus - Regulates satiety - Stimulated by Leptin - Damage leads to obesity and savage behavior

H1 Histone

- Located outside of the histone core (the other histones are inside the core) - Bind linker segments of DNA that lie between nucleosomes and facilitate packaging of nucleosomes into more compact structures - DNA associated with histones has the appearance of beads on a string - This structure undergoes further rounds of coiling and associates with other proteins (like nuclear scaffold protein), ultimately forming chromosomes

MHC 1

- Loci: HLA-A, HLA-B, HLA-C - Binding: TCR and CD8 - Expressed on all nucleated cells; NOT expressed on RBCs - Function: present ENDOGENOUSLY synthesized antigens (viral or cytosolic proteins) to CD8+ cytotoxic T cells - Antigen loading: Antigen peptides loaded onto MHC 1 in RER after delivery via TAP (transporter associated with antigen processing) - Associated proteins: beta2-microglobulin

MHC 2

- Loci: HLA-DP, HLA-DQ, HLA-DR - Binding: TCR and CD4 - Expressed on APCs - Function: present EXOGENOUSLY synthesized antigens (bacterial proteins) to CD4+ helper T cells - Antigen loading: Antigen loading following release of invariant chain in an acidified endosome - Associated proteins: invariant chain

Why do pts on long-term antipsychotic meds get Tardive Dyskinesia?

- Long-term blockade of dopamine receptors in the nigrostriatal dopamine pathway cause upregulation and compensatory supersensitivity of postsynaptic dopamine receptors

What are the symptoms of Lateral Medullary Syndrome (Wallenberg Syndrome)?

- Loss of pain and temp over contralateral body (spinothalamic tract damage) - Loss of pain and temp over ipsilateral face (spinal trigeminal nucleus damage) - Hoarseness, difficulty swallowing, loss of gag reflex (Nucleus ambiguus: CN 9 and 10) - Ipsilateral Horner Syndrome (descending sympathetic tract) - Vertigo, nystagmus, nausea/vomiting (Vestibular nuclei damage) - Ipsilateral cerebellar deficits (ataxia, past pointing); (inferior cerebellar peduncle damage)

Neonatal Vitamin K Deficiency

- Low vit K stores (poor placental transfer, sterile gut, low content in breast milk); Inefficient vit K utillization by immature liver - Presentation: Intracranial, GI, cutaneous, umbilical, and surgical site bleeding - Prevention: IM vit K at birth

What is derived from the first pharyngeal arch?

- M&T - Meckel's cartilage: Mandible, mandibular ligament, malleus and incus - Muscles of mastication: masseter, medial pterygoid, lateral pterygoid, temporalis; myohyoid, tensor tympani, tensor veli palatini, anterior 2/3 of tongue - Mandibular and maxillary branches of the trigeminal n

Abciximab

- MAB that inhibits platelet aggregation by targeting the platelet IIb/IIIa receptor

Vit B9 def

- Macrocytic, megaloblastic anemia; hypersegmented PMNs - Glossitis, no neurological symptoms (as opposed to B12 def) - Labs: increased homocysteine, normal methylmalonic acid levels - Most common Vit def in the US - seen in alcoholism and pregnancy - Def can be caused by several drugs (phenytoin, sulfonamides, methotrexate)

Vit B12 Def

- Macrocytic, megaloblastic anemia; hypersegmented PMNs - Paresthesias and subacute combined degeneration (degen of dorsal columns, lateral corticospinal tracts, and spinocerebellar tracts) due to abnormal myelin - Assoc with increased serum homocysteine and methylmalonic acid levels - Prolonged def --> irreversible nerve damage

Macrophage-lymphocyte interaction

- Macrophages and other APCs release IL-12, which stimulates T cells to differentiate into Th1 cells - Th1 cells release IFN-gamma to stimulate macrophages - Helper T cells have CD4, which binds to MHC II on APCs

How does chronic glucocorticoid use affect the bones?

- Major risk factor for osteoporosis - Decrease GI absorption of calcium, inhibit collagen synthesis by osteoblasts, decrease GnRH (leading to hypogonadism), and increase urinary calcium loss

Epithelial ovarian cancer

- Manifestations: abdominal distension, ascites, pleural effusion, bowel obstruction, decreased appetite, weight loss, and ovarian mass - Marker: Cancer antigen 125 (CA-125) - neither sensitive nor specific and can be found in normal tissue and other cancers

Prader-Willi syndrome

- Maternal imprinting: gene from mom is normally silent and paternal gene is deleted/mutated --> hyperplagia, obesity, intellectual disability, hypogonadism, and hypotonia

Superior vena cava syndrome - What is typically the cause? What are the signs?

- May be due to pancoast tumor of the lung (extensive smoking history, right-sided shoulder pain) - Signs: face and neck swelling, engorged neck veins, dyspnea and cough (due to laryngeal edema), arm and chest edema

Carotid sinus hypersensitivity

- May be triggered by pressure on the carotid sinus by a tight shirt collar - Leads to lightheadness, low blood pressure and low HR - Carotid sinus pressure or massage stimulates the baroreceptors and increases the firing rate from the carotid sinus --> increased parasympathetic output and withdrawal of sympathetic output to hear and vasculature --> low BP, low cardiac output, syncope

What are some physical manifestations of hyper-estrogenemia?

- May occur in pt with liver failure - Spider angiomas, palmar erythema, gynecomastia, testicular atrophy, decreased body hair and Dupuytren's contractures (1+ fingers become permanently stuck in bent position)

Case-fatality rate

- Measure of the severity of a disease - Proportion of reported cases of a specific disease that are fatal within the population affected by the disease over a specified time

HDL

- Mediates reverse cholesterol transport from the periphery to the liver - Acts as a repository for apolipoproteins C and E (which are needed for chylomicron and VLDL metabolism) - Secreted from both the liver and the intestine - Alcohol increases synthesis

What is vimentin stained to detect?

- Mesenchymal tissue (fibroblasts, endothelial cells, macrophages) - IDs: mesenchymal tumors (ex. sarcoma), but also endometrial carcinoma, renal cell carcinoma, and meningiomas

Nitroglycerin (Nitrates) - what is the physiology behind how they work?

- Metabolized within vascular smooth mm cells to nitric oxide --> activates guanylate cyclase and promotes conversion of cGTP to cGMP --> decreased intracellular calcium (reduced the activity of myosin light-chain kinase) and activation of myosin light chain phosphatase --> promotes myosin light-chain dephosphorylation and vascular smooth muscle relaxation

Name 5 types/causes of nephrotic syndrome

- Minimal change disease, focal segmental glomerular sclerosis, membranous glomerulopathy, diabetic nephropathy, amyloidosis

Minute ventilation vs. alveolar ventilation

- Minute ventilation: total volume of new air that enters the respiratory pathways per minute = tidal volume (L) X breaths/min - Alveolar ventilation: the volume of new air reaching the gas exchange areas per minute - does not include dead space volume = (tidal volume - dead space) X breaths/min

What is hypertrophic cardiomyopathy associated with?

- Mitral regurg secondary to impaired mitral valve closure --> systolic murmur

MAO

- Monoamine oxidase: responsible for degradation of monoamine neurotransmitters within the presynaptic nerve terminal

What does Burkitt lymphoma look like on LM?

- Monomorphic, intermediate-sized lymphocytes with round nuclei, multiple prominent nucleoli, and vacuolated basophilic cytoplasm - Typically see high mitotic index and high cell death rate - Benign macrophages that phagocytize the resulting celular debris ("tingible body macrophages") are diffucely distributed throughout the malignant tissue and clear spaces surround these macrophages --> "starry sky" appearance

IgG

- Most abundant isotype in serum - Fixes complement, crosses placenta (provides infants with passive immunity), opsonizes bacteria, neutralizes bacterial toxins and viruses

Fibroadenoma - what is it? What are some characteristics? Presentation? How does it change in size?

- Most common benign breast tumor and most frequently occurs in adolescent girls and young women - Tumor characterized by proliferation of stromal and ductal elements and is typically encapsulated by fibrous tissue - Gross path: tan-white and sharply demarcated from breast tissue - Presentation: solitary, well-demarcated, nontender, firm, spherical, and mobile nodule; its epithelial component is estrogen-sensitive, resulting in a size increase in pregnancy or luteal phase of menstrual cycle - decreases in size postpartum and after menopause

Hamartoma

- Most common benign lung tumor - Usually present as an incidental finding on chest x-ray with the appearance of a well-defined coin lesion with "popcorn calficiations" - An excessive growth of a tissue type native to the organ of involvement - Lung is most common location: usually contain islands of mature hyaline cartilage, fat, smooth m and clefts lined by respiratory epithelium

Posterior urethral valves

- Most common cause of bilateral fetal hydronephrosis in boys - Caused by an obstructive, persistent urogenital membrane at the junction of the bladder and urethra

Focal segmental glomerulosclerosis

- Most common cause of nephrotic syndrome in adults - LM: obliterated capillaries with hyalin deposition (sclerosis) - sclerosis is focal (only certain glomeruli affected) and segmental (only portions of the glomeruli are affected) - EM: podocyte effacement and fusion - Does not respond well to tx - causes end stage renal disease - Caused by: heroin abuse, diabetes, HTN, vasculitis, sickle cell, HIV, hepatitis

Fibrocystic changes of the breast

- Most common cause of palpable nodular masses in the breast - Fibrocystic disease presentation: poorly defined, diffuse increase in cysts and fibrotic tissue throughout the breasts - lesions are often numerous and painful with maximal tenderness during the premenstrual phase of the cycle

Diffuse Proliferative Glomerulonephritis

- Most common presentation of nephritic syndrome in SLE pts - Subendothelial deposits of anti-DNA Abs - Capillary wall thickening - "wire loop" - IF: granular staining pattern - Tx: corticosteroids

Glioblastoma

- Most common primary brain tumor in adults - From astrocytes; life is 6mo-1yr, usually in the cerebral hemispheres - Pseudopalisading pattern (snake-like)

Pilocystic astrocytoma

- Most common primary brain tumor in children - Usually in posterior fossa, increased GFAP - Rosenthal fibers: eosinophilic cork screw

Cardiac myxomas: What are they? What does it look like on biopsy?

- Most common primary cardiac neoplasms - usually originating in the left atrium - Left atrial myxomas can obstruct blood flow across the mitral valve --> syncope and symptoms of heart failure - Biopsy: numerous bland stellate cells in a background of myxoid ground substance

Myxoma

- Most common primary heart tumor in adults - 90% occur in the left atrium - associated with multiple syncopal episodes - Usually described as a "ball valve" obstruction in the left atrium - May hear early diastolic "tumor plop" sound

Ornithine transcarbamylase deficiency

- Most common urea cycle disorder; X-linked Rec - Interferes with body's ability to eliminate ammonia - Often evident in the first few days of life, but may present later - Excess carbamoyl phosphate is converted to orotic acid (part of the pyrimidine synthesis pathway) - Findings: increased orotic acid in blood and urine, decreased BUN, symptoms of hyperammonia - No megaloblastic anemia (vs. orotic acid)

Alcoholic cerebellar degeneration - What is the most likely cause? What is the pathophysiology? Symptoms?

- Most likely due to Thiamine def - Pathophysiology: loss of Purkinje cells in the anterior lobes and cerebellar vermis - Symptoms: atazia that progresses over weeks to months before eventually stabilizing - wide-based gait ataxia; truncal instability, intention tremor of the hands and fingers, and a rhythmic, postural "Parkinsonian" tremor of the fingers and hands

Nephropathy of multiple myeloma

- Most often due to excess excretion of free light chains (Bence Jones proteins) that precipitate with Tamm-Horsfall protein to form obstructing tubular casts (cast nephropathy) - these casts are seen as amorphous hyaline material in the tubular lumen

What diseases are HLA-DR2 associated with?

- Multiple sclerosis, hay fever, SLE, Goodpasture syndrome

What is desmin stained to detect?

- Muscle - IDs: Muscle tumors (rhabdomyosarcoma)

What are the essential amino acids?

- Must be supplied in the diet - Glucogenic: methionine (Met), Valine (Val), Histidine (His) - Glucogenic/Ketogenic: Isoleucine (Ile), Phenylalamine (Phe), Threonine (Thr), Tryptophan (Trp) - Ketogenic: Leucine (Leu), Lysine (Lys)

Hereditary hemochromatosis - What is the mutation? What is it? Triad? Labs?

- Mutation: Hfe gene on Ch6 - Hemosiderin (iron) deposition and organ damage in the liver, pancreas, and myocardium as well as melanin deposition in the skin - Triad: micronodular cirrhosis, diabetes mellitus, skin pigmentation (bronze diabetes) - Labs: marked elevated serum transferrin saturation because of combination of increased serum iron and decreased total iron binding capacity (TIBC)

Locus heterogeneity

- Mutations at different loci can produce a similar phenotype - Ex: albinism

McArdle disease

- Myophosphorylase deficiency - Myopathy due to improper breakdown and subsequent accumulation of glycogen in skeletal muscle - Presentation: mm cramps, fatigue, myoglobinuria (red urine) after short bursts of strenuous exercise

Ethanol metabolism (pic)

- NAD+ is the limiting reagent

Glucose-6-phosphate dehydrogenase def (physiology)

- NADPH is required to keep glutathione reduced, which detoxifies free radicals and peroxides - Decrease in NADPH in RBCs --> hemolytic anemia due to poor RBC defense against oxidizing agents (ex. fava beans, sulfonamides, primaquine, anti-TB drugs) - Infection can also precipitate hemolysis - inflammatory response --> free radicals that diffuse into RBCs --> oxidative damage

Vit C excess

- Nausea, vomiting, diarrhea, fatigue, calcium oxalate nephrolitiasis - Can increase risk of iron toxicity in predisposed individuals (ex. those with transfusions, hereditary hemochromatosis)

Vit K def

- Neonatal hemorrhage with increased PT and aPTT but normal bleeding time (Neonates have sterile intestines and are unable to make Vit K) - typically give Vit K injection at birth - Can also occur after prolonged use of antibiotics

Post-strep glomerulonephritis

- Nephritic syndrome - After group A strep pharyngitis or skin infection - EM: immune complex deposition in mesangium - can see subendothelial and subepithelial humps - LM: hypercellular glomerulus and neutrophil infiltrate into glomerulus - IF: granular patterns - Dx: won't be able to culture bacteria (already gone); measure serum anti-streptolysin O and anti-DNAse B titers

Dense Deposit Disease

- Nephritic syndrome - LM similar to membranoproliferative glomerulonephritis - with tram-track appearance - Deposits of unknown material in BM - NOT immune complex deposition - Looks like a black line outlining the capillaries - Assoc with C3 nephritic factor --> very low C3 levels in serum, C4 is normal

Membranoproliferative Glomerulonephritis

- Nephritic syndrome - LM: hypercellularity and lobular appearance - GBM thickening due to mesangial cell proliferation - Tram-track appearance - Causes: viral (Hep B or C), bacterial (endocarditis, shunt nephritis), autoimmune (IC formation) - IF: ICs in subendothelial space, granular pattern

Rapidly Progressive Glomerulonephritis

- Nephritic syndrome - Rapid decrease in kidney function --> death in weeks-months - Crescents in glomeruli 3 Types: - Immune-mediated: segmental necrosis and breaks in BM - plasma and fibrin break through; granular pattern on IF - Pauci-immune Anti-GN: no IC deposition - may be associated with c-ANCA or p-ANCA - Goodpasture's disease: Auto-Abs against collagen IV in BM - renal and pulmonary problems - LINEAR pattern on IF

Rett Syndrome - What is presentation? What is the most common mutation that causes this?

- Neurodevelopment disorder that is mainly in girls - Normal development until age 5-18 months then loss of motor and language skills and the development of stereotypic hand movements - Deceleration of head growth: classic feature and can be an early sign - Can also get: seizures, ID, autistic features, and breathing abnormalities - Most cases due to de novo mutations in the X-linked MECP2 gene

What is GFAP stained to detect?

- Neuroglia (astrocytes, Schwann cells, oligodendroglia) - IDs: astrocytoma, glioblastoma

What are the major adverse effects of Ganciclovir?

- Neutropenia, anemia, thrombocytopenia, and impaired renal function - Used to tx CMV

What are the primary cell lines that are increased in stable COPD?

- Neutrophils, macrophages, and CD8+ T lymphocytes - release enzymes and proteases such as neutrophil elastase that cause alveolar damage, reduced ciliary motion, and increased mucus secretion by goblet cells - The inflammatory cells show impaired ability to phagocytize bacterial pathogens, possibly contributing to increased risk of respiratory infections such as community acquired pneumonia

Function of Vit B3

- Niacin - Constituent of NAD+ and NADP+ (used in redox reactions) - Derived from tryptophan - Synthesis required Vit B2 and B6 - Used to tx dyslipidemia: lowers VLDL and raises HDL

Nicotinic acid: uses, side effects (what are they mediated by?)

- Niacin - Used in the tx of hyperlipidemia - effective in raising HDL as well as lowering triglycerides and LDL levels - Side effects: cutaneous flushing, warmth, itching - mediated by release of prostaglandins - aspirin can reduce these side effects if given 30-60 mins before niacin administration

Vit A Deficiency

- Night blindness, dry, scaly skin, corneal degeneration, bitot spots on conjunctiva, immunosuppression

What medication can be given to improve morbidity and mortality in a pt with a subarachnoid hemorrhage?

- Nimodipine: a Ca2+ channel blocker

Isolated systolic hypertension

- Normal diastolic BP with systolic BP over 140 - Often seen in pts over the age of 60 due to increased arterial stiffness caused by endothelial dysfunction and a change in extracellular matrix composition (decreased elastin, increased collagen deposition) - Can also result from an increase in cardiac output due to severe aortic regurg or systemic causes (anemia, hyperthyroidism)

When might you hear splitting of the S2 heart sound?

- Normal during inspiration - Pulmonary stenosis, right bundle branch block

Activation of NF-kB

- Normally in an inactive state bound to its inhibitor IkB - Classical activation pathway: an extracellular signal, such as binding of bacterial antigens to a toll-like receptor, causes activation of IkB kinase --> ubiquination and subsequent destruction of IkB with the release of free NF-kB --> enters the nucleus and promotes the synthesis of a number of inflammatory proteins such as cytokines, acute phase reactants, cell adhesion molecules, and leukocyte-related growth factors - This cascade is self-limiting: NF-kB stimulates the transcription of more IkB which rebinds to the freed NF-kB

Where is growth hormone normally secreted from? Its growth promoting effects are primarily mediated by what enzyme?

- Normally secreted from the anterior pituitary - Growth-promoting effects: mediated by insulin-like growth factor-1 (IGF-1) secreted from the liver following stimulation of hepatic GH receptors and subsequent activation of the JAK-STAT signaling pathway

What is the pathogenesis behind keloid formation?

- Normally, TGF-beta promotes differentiation of fibroblasts into myofibroblasts which should diminish on wound repair. - In keloids: TGF-beta is produced excessively without regulation --> keloid extends beyond the border of the original wound, do not regress, and often recur after resection

What does secretin do normally? What about in the presence of gastrinomas?

- Normally: released from duodenum in response to acid and fat in the small intestine --> increased pancreatic bicarbonate secretion and inhibits the release of gastrin from normal gastric G cells - Gastrinoma: paradoxically stimulates gastrin release due to abnormal adenylate cyclase activation - Secretin administration can be used to differentiate ZES from other causes of hypergastinemia (atrophic gastritis)

What part of the cell cycle does nucleotide excision repair occur? In what disease is it defective? Mismatch repair?

- Nucleotide Excision Repair: G1; Xeroderma Pigmentosum - prevents repair of pyrimidine dimers because of UV light exposure - Mismatch Repair: G2; Lynch syndrome

How are pyrimidine dimers removed after UV damage?

- Nucleotide excision repair: a specific endonuclease complex detects abnormalities in the DNA structure caused by the formation of DNA photoproducts. The endonuclease complex nicks the damaged strand on both sides of the pyrimidine dimer and the defective region is excised - DNA polymerase synthesizes new DNA in the place of damaged DNA and DNA ligase seals the final remaining nick

What is osteoprotegerin (OPG)? What is its effect on RANK-L and what does this lead to?

- OPG blocks the interaction between RANK and RANK-L by acting as a decoy receptor - By binding to RANK-L, OPG reduced differentiation and survival of osteoclasts --> decreased bone resorption and increased bone density - Bone turnover is regulated by the ratio or OPG to RANK-L (increases when OPG is low and RANK-L is high) - Estrogen induces the production of OPG by osteoblasts and stromal cells (low estrogen --> low OPG --> more bone turnover

Complete hytidiform mole - what is it? What are its characteristics? How do you distinguish from a partial mole? Presentation? Sonograph finding?

- Occurs due to abnormal proliferation of placental precursor cells (cytotrophoblasts and syncytiotrophoblasts) - Characterized by complete absence of embryonic or fetal tissue due to paternal imprinting - chromosomal component is 46, XX or 46, XY but is all from sperm - Distinguished from a partial mole because a complete mole is p57 negative - p57 protein is the product of a paternally imprinted but maternally expressed gene - Presentation: vaginal bleeding, extremely high beta-hCG levels, and "snowstorm" pattern on ultrasound - Classic sonograph finding: central heterogeneous mass with numerous discrete anechoic spaces corresponds histologically with trophoblastic hyperplasia and edematous chorionic villi

Fat embolism syndrome

- Occurs in 10% of patients with severe skeletal injuries and is characterized by pulmonary insufficiency, diffuse neuro impairment, thrombocytopenia, and anemia - Fat globules dislodged from bone marrow enter the marrow vascular sinusoids and then occlude pulmonary microvessels, impairing gas exchange - Microvascular occlusion in the cerebral white matter, brain stem, and spinal cord causes the neurological manifestations

Positive selection of T cells

- Occurs in the thymic cortex - T Cells expressing TCRs capable of binding self-MHC on cortical epithelial cells survive

Negative selection of T cells

- Occurs in the thymic medulla - T cells expressing TCRs with high affinity for self antigens undergo apoptosis - Tissue-restricted self antigens are expressed in the thymus due to the action of autoimmune regulator (AIRE); deficiency leads to autoimmune polyendocrine syndrome-1

Phenotype mixing

- Occurs when a host cell is coinfected with 2 viral strains and progeny virions contain parental genome from one strain and nucleocapsid (or envelope) proteins from the other strain - Genome is unchanged and does not pass on to progeny

Opsonization - what is it? What are the most important opsonins?

- Occurs when host proteins such as Igs or complement bind to the surface of foreign cells to promote phagocytosis - Most important opsonins: IgG and complement C3b - Mannose-binding lectin and C-reactive protein can also opsonize cells

Pleiotropy

- One gene contributes to multiple phenotypic effects - Ex: Untreated PKU manifests as light skin, intellectual disability, and musty body odor

Membranous nephropathy - What causes it? What does it look like on LM? EM?

- One of the most common causes of nephrotic syndrome in adults - Results from immune complex deposition in the subepithelial portion of glomerular capillary walls - LM: Jones methenamine silver stain - shows thickening of the glomerular basement membrane - the immune complex deposits do not take up the silver stain so they form pale areas with intervening regions of darkly-staining basement membrane that appear as irregular spikes - EM: subepithelial deposits - Often idiopathic, but can occur in the presence of a solid tumor (lung or colon), chronic infection, or autoimmune disease

Necrotizing enterocolitis - What is it? Who is most likely to get it? Why? Pathophys? What are survivors at risk of? Appearance on abdominal XRay?

- One of the most frequent GI emergencies affecting newborns - mostly in preterm infants secondary to GI and immunologic immaturity - Upon initiation of enteral feeding, bacteria are introduced into the bowel where they proliferate excessively due to compromised immune clearance - impaired mucosal barrier function allows the bacteria to invade the bowel wall, causing inflammation and ischemic necrosis of the terminal ileum and colon --> bowel becomes congested and gangrenous with the formation of intramural gas collections - Survivors are at risk for strictures and bowel obstruction secondary to fibrosis that occurs as the inflammation subsides - Abdominal Xray: thin, curvilinear areas of lucency that parallel the lumen

What is positive selection of T cells and where does it occur?

- Only T cells expressing a TCR that is able to bind self MHC are allowed to survive. Others that have a TCR the is not specific for self MHC are signaled for elimination via apoptosis - Occurs in the thymic cortex and involves interaction of T cells with thymic cortical epithelial cells expressing self MHC - Responsible for the T cell repertoire that can recognize self - Occurs before negative selection

When are benzos an appropriate tx for delirium?

- Only when the delirium is due to alcohol or benzos withdrawal

What is the heart sound heard with mitral stenosis?

- Opening snap heard shortly after S2 heart sound followed by a diastolic rumbling murmur as the result of turbulent flow through the stenotic mitral valve during left ventricular filling

Ilioinguinal n

- Originates from L1 n root - Accompanies the spermatic cord through the superficial inguinal ring - Provides sensation to the upper and medial thigh and pars of the external genetalia

What is the most common defect of the urea cycle? What are the manifestations of this defect?

- Ornithine transcarbamoylase deficiency - Typically present in the mitochondria - Pres: results in accumulation of carbamoyl phosphate which is converted to orotic acid by the pyrimidine biosynthetic pathway; also get hyperammonemia

What are 3 possible mechanisms that can lead to a lung abscess?

- Oropharyngeal Aspiration: most common cause; often contain mixed aerobic and anaerobic oral flora such as Peptostreptococcus, Prevotella, Bacteroides, and Fusobacterium species; Risk factors include loss of consciousness or dysphagia wuch as with alcoholism, drug overdose, seizure disorders, prolonged anesthesia, and severe neurologic disorders - Complication of Bacterial Pneumonia: predisposing factors include immunosuppression, old age, and chronic lung disease; necrotizing pneumonias are usually nosocomial and caused by Staph Aureus, E Coli, Klebsiella Pneumoniae, and Pseudomonas - Hematogenous Spread: in pts with septicemia or infectious endocarditis - usually Staph or Strep infections

Lactase Deficiency

- Osmotic diarrhea: similar mechnism to osmotic laxitives like polyethylene glycol and magnesium citrate - Inherited or acquired deficiency of the intestinal brush border enzyme lactase --> can't break down lactose into glucose and galactose --> lactose is a nonabsorbable osmotic substance - Presentation: abdominal pain, distension, and watery diarrhea with decreased stool pH - Abdominal pain and distention are caused by metabolism of lactose by normal gut flora through fermentation --> increased gas production - Normal appearing villi

Why is Paclitaxel given to pts that have a coronary stent placed?

- Paclitaxel: antineoplastic agent that functions by binding b-tubulin and preventing microtubule breakdown thus causing the arrest of the cell cycle in the M phase --> ultimately prevents intimal hyperplasia, which could cause restenosis of the vessel

Anserine bursitis

- Pain along the medial knee and well-defined tenderness approximately 4 cm distal to the anteromedial joint margin of the knee - Results from obesity or overuse in athletes

What are 6 key enzymes in lipid transport? What do they do and where do they function?

- Pancreatic lipase: degradation of dietary triglycerides (TGs) in the small intestine - Lipoprotein lipase: degradation of TGs circulating in chylomicrons and VLDLs. Found on vascular endothelial surface - Hepatic TG lipase: degradation of TGs remaining in IDL - Hormone-sensitive lipase: degradation of TGs stored in adipocytes - LCAT: catalyzes esterification of cholesterol - Cholesterol ester transfer protein (CETP): mediates transfer of cholesterol esters to other lipoprotein particles

Function of Vit B5

- Pantothenic acid - Essential component of CoA (a cofactor for acyl transfers) and fatty acid synthesis

Pineal tumors

- Part of the dorsal midbrain - Usually cause obstructive hydrocephalus with symptoms of increased intracranial pressure (headache, vomiting, altered mental status) and Parinaud syndrome (upward gaze palsy)

Angelman syndrome

- Paternal imprinting: gene from dad is normally silent and maternal gene is deleted/mutated --> inappropriate laughter ("happy puppet"), seizures, ataxia, and severe intellectual disability

Pathogenesis of Wilson disease

- Pathogenesis: AR mutation of ATP7B --> hepatic copper accumulation --> leak from damaged hepatocytes --> deposits in tissues (basal ganglia, cornea)

Features of chronic granulomatous disease

- Pathogenesis: inactivating mutation affecting NADPH oxidase; impaired respiratory burst inhibits phagocytic intracellular killing - Clinical manifestations: recurrent infections with catalase-positive bacteria and fungi (Staph A, Burkholderia cepacia, Serratia marcescens, Nocardia, and Aspergillus); lungs, skin, lymph nodes, and liver most commonly involved; diffuse granuloma formation - Dx: measurement of neutrophil superoxide production (DHR flow cytometry (preferred), NBT testing

Inflammatory breast cancer

- Peau d'orange rash: characterized by a generalize erythematous rash that is often itchy; skin texture is firm and coarse, similar to an orange peel - Rapidly progressive derm finding and breast edema --> inflammatory breast cancer - Findings are due to cancerous cells obstructing lymphatic drainage after spread to the dermal lymphatic spaces - May be confused with mastitis: lack of fever and long symptom duration point to a noninfectious process

HMP shunt

- Pentose Phosphate pathway - Provides a source of NADPH form the abundantly available Glucose-6-phosphate - Yields ribose for nucleotide synthesis and glycolytic intermediates - 2 distinct phases (oxidative and nonoxidative), both of which occur in the cytoplasm - No ATP is used or produced - Sites: lactating mammary glands, liver, adrenal cortex (sites of fatty acid and steroid synthesis), RBCs

What are the dominant organisms in the oral cavity that might be isolated from cultures from pts with aspiration pneumonia?

- Peptostreptococcus, Bacteroides, Prevotella, Fusobacterium

What stain is used to ID glycogen storage diseases?

- Periodic acid-Schiff stain IDs glycogen

What diseases are associated with HLA-DR5?

- Pernicious anemia --> vit B12 def; Hashimoto thyroiditis

Poison Ivy Reaction

- Poison ivy, oak, and sumac: produce urushiol - a small allergenic substance that causes an immune reaction when attached to proteins (a hapten) - Type 4 (delayed type) hypersensitivity reaction: mediated by T cells - typically CD8+ cells are the primary effector cells and directly destroy keratinocytes expressing haptenated proteins

What is the major virulence factor for H flu?

- Polysaccharide capsule: composed of the polymer polyribosylribitol phosphate (PRP) - protects the bacterium against phagocytosis and complement-mediated lysis by binding factor H, a circulating complement control protein that prevents complement deposition on host cells

What structures run through the cavernous sinus?

- Posterior communicating artery (off internal carotid) - CN nerves 3 (ptosis, mydriasis), 4, 6, V1 and V2 (loss of upper facial sensation and the afferent limb of the corneal reflex) - Pituitary gland - Optic chiasm lies above this sinus

Placental abruption

- Premature detachment of the placenta from the uterine wall prior to the delivery of the fetus - Signs: painful prolonged uterine contractions, a tense abdomen, and vaginal bleeding prior to delivery

Risks of secondhand smoke exposure to an infant

- Prematurity, low birth weight - Sudden infant death syndrome - up to 50% of all SIDS cases are due to secondhand smoke exposure - Middle ear disease (Otitis media) - Asthma - Respiratory tract infections (bronchitis, pneumonia)

Repetitive anterior knee trauma (such as kneeling all day) may result in injury to what structure?

- Prepatellar bursitis ("housemaid's knee") - The prepatellar bursa is located between the patella and the overlying skin - May also be seen in carpet layers, mechanics and plumbers

Somatostatinoma

- Presentation: abdominal pain, gallbladder stones, constipation, hyperglycemia and steatorrhea - Due to somatostatin-induced inhibition of insulin, glucagon, gastrin, secretin, and CCK as well as inhibition of GI motility

Klinefelter syndrome - What is the presentation? what is the mutation?

- Presentation: gynecomastia, sparse body hair, and primary hypogonadism, increased length of long bones, azoospermia (semen contains no sperm), and ID - Chromosomal nondisjunction: 47, XXY genotype - Typically have atrophied, hyalinized seminiferous tubules, resulting in small, firm testes and low inhibin levels - Leydig cells are abnormal --> decreased testosterone levels --> lack of feedback inhibition --> increased FSH and LH --> increased aromatase activity and elevated estrogen production

VIPoma

- Presentation: intractable diarrhea, hypokalemia, and achlorhydria - Pts usually hypotensive due to dehydration and the vasodilatory effects of VIP

Kaposi's sarcoma - Presentation? What is it associated with?

- Presentation: multiple blue-violet or brownish dermal plaques that first appear on the feet and legs before spreading proximally - can develop on the mucosal membranes of the face and genitals - Histo: spindle and endothelial cell proliferation, RBC extravasation, and inflammation - Strongly associated with both HIV and human herpes virus type 8 (HHV-8)

Dermatitis herpetiformis - What is the presentation? What does it look like on LM? What is it associate with? Tx?

- Presentation: pruritic, grouped vesicles on the extensor surfaces - LM: accumulations of neutrophils on the tips of dermal papillae (microabscesses) - Associated with: Celiac disease - Tx: Dapsone, gluten-free diet

Zollinger-Ellison syndrome

- Presents as distal duodenal ulcer and high-normal gastrin levels that rise in response to secretin - Caused by gastric-secreting tumors that are usually located in the small intestine or pancreas - Increased gastrin --> parietal cell hyperplasia and stimulates gastric acid secretion --> development of peptic ulcers, heartburn, and diarrhea - Ulcers are usually located beyond the duodenal bulb (proximal duodenal ulcers suggest H Pylori infection or NSAID use)

Bile acid sequestrants

- Prevent reabsorption of bile acids in the intestine - Decreases LDL - Side effects: nausea, bloating, cramping, impaired absorption of drug and fat soluble vitamins

What does Clavulonic acid do?

- Prevents enzymatic destruction of an antibiotic - inhibits bacterial beta-lactamase, preventing destruction of penicillin-family antibiotics

Medulloblastomas

- Primarily arise from the posterior fossa (cerebellum) - Presentation: symptoms of increased ICP and cerebellar dysfunction (dizziness, gait ataxia, nystagmus)

Oligodendroma

- Primary brain tumor - Fried egg appearance - perinuclear cytoplasmic clearing

Schwannoma

- Primary brain tumor usually in CN 8 - Hearing problems, dizziness - Associated with NF 2

What is negative selection of T cells? Where does it occur?

- Process by which T cells possesing TCRs that bind with high affinity to self antigen or self MHC class 1 or 2 are eliminated by apoptosis - Occurs in the thymic medulla and involves interaction of the developing T cells with thymic medullary epithelial cells and dendritic cells - Eliminates T cells that may be overly autoreactive against self antigens and may play a role in autoimmunity if not destroyed - Results in T cells with only an appropriately low affinity for self MHC molecules

5-Hydroxyicosatetraenoic acid (5-HETE)

- Produced by a variety of immune cells - Serves as a leukotriene and lipoxin precursor - Causes neutrophil and macrophage chemotaxis and neutrophil degranulation

IL-1

- Produced by macrophages and epithelial cells - Pro-inflammatory properties: endothelium activation, increased chemokine expression (promoting leukocyte recruitment) and induction of fever - Promotes Th0 --> Th1 and Th2

TNF-alpha

- Produced by macrophages, NK cells, and T cells - Promotes leukocyte recruitment and activates the endothelium (increased expression of adhesion molecules)

How does a prolactinoma affect GnRH, LH, and testosterone?

- Prolactin suppresses GnRH secretion --> reduces LH from the pituitary and reduces testosterone from the testicles

Kwashiorkor

- Protein malnutrition --> skin lesions, edema due to decreased plasma oncotic pressure, liver malfunction (fatty change due to decreased apolipoprotein synthesis)

What causes frothy, foamy urine?

- Proteinuria or bile salts in urine

Idiopathic Intracreanial Hypertension

- Pseudotumor cerebri - Typically present in young obese women with daily headache, bilaterally symmetric papilledema, and transient visual disturbances related to impaired cerebral venous outflow and elevated intracranial pressure - Symptoms worsen with valsalva maneuver or bending down - Build up of pressure compresses the optic nerves externally, which in turn impairs axoplasmic flow within the optic nerves, causing bilateral optic disc edema - Fundoscopic exam: high elevated of the optic disc and blurred disc margins (papilledema)

What diseases are HLA-B27 associated with?

- Psoriatic arthritis, Ankylosing spondylitis, IBD-associated arthritis, Reactive arthritis - "PAIR"

Describe Internuclear Opthalmoplegia. Where is the lesion?

- Pt can abduct eye normally, but cannot adduct eye - plus nystagmus in the abducting eye - Medial Longitudinal Fasciculus lesion

Iliopsoas test

- Pt is asked to flex at the hip against resistance applied by the examiner at the anterior knee - if pain occurs, the psoas sign is positive - Positive sign: inflammation of the psoas muscle or its overlying parietal peritoneum, psoas abscesses and appendicitis

What nerve innervates the external urethral sphincter?

- Pudendal n - Side note: the Internal urethral sphincter is controlled by the sympathetic nervous system

What are the 4 cardiac malformations in Tetralogy of Fallot? What murmur is heard?

- Pulmonary stenosis - RV hypertrophy - Overriding aorta - Ventricular septal defect - Harsh systolic ejection murmur and a systolic thrill at the left sternal border

Alcoholic cerebellar degeneration

- Purkinje cell degeneration in the cerebellar vermis - Presentation: truncal ataxia, with abnormal heel-to-shin test

Thiamine is a cofactor for what enzymes in glucose metabolism?

- Pyruvate dehydrogenase: converts pyruvate (glycolysis end product) into acetyl-CoA (enters citric acid cycle) - alpha-Ketoglutarate dehydrogenase: an enzyme of the citric acid cycle - Branched-chain alpha-ketoacid dehydrogenase: essential for catabolism of branched-chain amino acids (leucine, isoleucine, valine) - Transketolase: an enzyme of the pentose phosphate pathway that helps convert ribulose 5-P (derived from glucose) to glycolysis intermediates (ex. glyceraldehyde 3-P)

What do RNA Poly 1, 2, and 3 make?

- RNA Poly 1: rRNA - RNA Poly 2: mRNA - RNA Poly 3: tRNA

What are the defects seen in Tetralogy of Fallot?

- RV outflow obstruction - usually pulmonary valve stenosis - RV hypertrophy - Ventricular septal defect - Overriding Aorta - May see boot shaped heart on CXR

What nerve is most likely damaged from a fracture of the mid-shaft of the humerus in the region of the spinal groove? Signs of this nerve damage?

- Radial nerve - Weakness in wrist extension (wrist drop)

Glucagonoma

- Rare tumor arising from the alpha cells of the pancreatic islets - Necrolytic migratory erythema, erythematous plaques on face, perineum, and extremities, lesions enlarge and coalesce leaving a central indurated area (brown or bronze colored) with peripheral blistering and scaling - Diabetes mellitus/hyperglycemia - GI symptoms (diarrhea, anorexia, abdominal pain) - Dx: markedly elevated glucagon levels - Low levels of amino acids

Cilostazol

- Reduces platelet activation by inhibiting platelet phosphodiesterase - the enzyme responsible for breakdown of cAMP - Also acts as a direct vasodilator - Net effect: decrease in claudication symptoms and an increase in pain-free walking distance in pts with peripheral artery disease

Obstructive sleep apnea

- Reductions or cessation of airflow during sleep due to upper airway obstruction despite adequate respiratory effort - Ventilation remains nearly constant during the non-apneic periods with minimal cyclical variation in tidal volume

Fc Region of antibody

- Region of IgM and IgG that fixes complement - Heavy chain contributes to both Fc and Fab regions - The four Cs: Constant, Carboxy terminal, Complement binding, Carbohydrate side chains - Determines isotype (IgM, IgD, etc)

Dorsomedial nucleus of the hypothalamus

- Regulates hunger - Stimulation leads to obesity and savage behavior

How is the severity of chronic bronchitis measured?

- Reid index: Ratio of the thickness of hte mucous gland layer to the thickness of the wall between he epithelium and the cartilage - normal = 0.4 - As chronic bronchitis progresses, both the total bronchial wall thickness and the Reid index increase

Pulmonary actinomyces

- Relatively rare; develops most commonly by aspiration which often leads to lower lobe sonsolidation with air bronchograms (air-filled bronchi with surrounding alveolar opacification) - Pts with alcoholism are at increased risk - Dx: ID bacteria with unique filamentous, branching patterns and the characteristic sulfur granules which are formed by calcified mycelial fragments --- These sulfur granules grossly appear yellow, but on H&E stain appear purple/blue Tx: Penicillin

Somatostatin

- Released by delta cells - Inhibits gastrin release - if absent, high gastrin levels act both directly and indirectly to increase H+ ion secretion by parietal cells --> duodenal ulceration and duodenal gastric metaplasia - May be decreased by H. Pylori infection

N-acetylglutamate synthase deficiency

- Required cofactor for carbamoyl phosphate synthetase I; absence --> hyperammonia - Presents in neonates as poorly regulated respiration and body temperature, poor feeding, developmental delay, intellectual disability (identical to presentation of carbamoyl phosphate synthetase I deficiency)

Pygmalion effect

- Researcher's beliefs in the efficacy of treatment can potentially effect the outcome

Hemolytic disease of the newborn

- Results from Rh incompatibility or ABO incompatibility btwn mother and fetus - Pt develops jaundice on the first day of life due to indirect hyperbilirubinemia - Positive direct Coombs (antiglobulin) test confirms the presence of antibody-mediated hemolysis

Vesicoureteral reflux

- Results from incomplete closure at the vesicourethral junction ( where ureter meets bladder) and can lead to chronic dilation of the ureter and renal pelvis (either unilateral or bilateral) - Nonobstructive cause of fetal hydronephrosis

What diseases are associated with HLA-DR4?

- Rheumatoid arthritis, diabetes mellitus type 1, Addison disease

Function of Vit B2

- Riboflavin - Component of flavins FAD and FMN, used as cofactors in redox reactions (ex. the succinate dehydrogenase reaction in the TCA cycle)

Vit D def

- Rickets: in kids; bone pain and deformity - Osteomalacia: in adults; bone pain and mm weakness; hypocalcemic tetany - Breastfed infants should receive oral Vit D - Def is exacerbated by low sun exposure, pigmented skin, prematurity

Meningiomas

- Risk factors include: women, radiation exposure, NF type 2 - Slow growing primary brain tumor - Whorled pattern with psammoma bodies

What are risk factors and protective factors for epithelial ovarian cancer?

- Risk factors: family hx, infertility, nulliparity, PCOS, endometriosis, BRCA1 or BRCA2 mutations, Lynch syndrome, postmenopausal hormone therapy - Protective factors: combined oral contraceptives, multiparity, breastfeeding, salpingo-oophorectomy

How to test for von Willebrand factor deficiency?

- Ristocetin test: pt will have poor platelet aggregation in the presence of Ristocetin - If pt is given normal plasma, platelet aggregation will be normal in presence of Ristocetin

What are Southern blot, Northern blot, and Western blot tagging? Southwestern?

- SNoW DRoP - Southern: DNA - Northern: RNA - Western: Protein - Southwestern: DNA-binding proteins

What are the most common medications associated with impotence?

- SSRIs, sympathetic blockers (clonidine, methyldopa, beta-blockers)

Vit C def

- Scurvy: swollen gums, bruising, petechiae, hemarthrosis, anemia, poor wound healing, perifollicular and subperiosteal hemorrhages, "corkscrew" hair - Weakened immune system

What can chronic kidney disease cause? Why?

- Secondary hyperparathyroidism - Pts with chronic kidney disease are not able to make Vit D appropriately. Also, failure of glomerular and tubular function results in phosphate retention and hypocalcemia - Hypocalcemia, hperphosphatemia, and low Vit D --> compensatory increase in PTH - Secondary hyperparathyroidism signs: weakness, bone and muscle pain, abnormal bone mineralization, and increased risk of fractures

IFN-y

- Secreted by Th1 cells - Promotes pro-inflammatory pathways by activating macrophages, increasing antigen presentation, and inducing death of epithelial cells

IL-5

- Secreted by Th2 cells - Promotes the humoral response by stimulating differentiation of B cells and increasing IgA production - Promotes growth and differentiation of eosinophils - implicated in the pathogenesis of many allergic diseases (such as asthma)

Atrial natriuretic peptide

- Secreted by atrial cardiomyocytes in response to atrial stretch, which indicates systemic volume expansion - Ultimately it lowers BP through peripheral vasodilation, natriuresis, and diuresis - Works via cGMP

Why is von Willebrand factor important? What are the clinical features of von Willebrand disease?

- Secreted by endothelial cells - Increases stability of clotting factor 8 and is responsible for augmenting platelet binding at endothelial injury sites - helps in initial platelet plug formation - Pts have increased bruising and mucosal bleeding - prolonged bleeding during dental procedures and heavy menstrual periods (symptoms are typically mild)

Flow of aqueous humor in the eye

- Secreted by epithelial cells of the ciliary body into the posterior chamber of the eye --> flows through pupil into the anterior chamber to the iridocorneal angle --> diffuses through a trabecular network into Schlemm's canal (scleral venous sinus) --> drains into episcleral and conjunctival veins

IL-12

- Secreted by macrophages - Induces differentiation of Th1 cells and activation of NK cells

VLDL

- Secreted by the liver - Delivers hepatic TGs to peripheral tissues

Th1 Cell

- Secretes IFN-gamma - Activates macrophages and cytotoxic T cells - Differentiation induced by IFN-gamma and IL-12 - Inhibited by IL-4 and IL-10 (from Th2 cell)

Th2 cell

- Secretes IL-4, Il-5, IL-10, IL-13 - Recruits eosinophils for parasite defense and promotes IgE production by B cells - Differentiation induced by IL-4 - Inhibited by IFN-gamma (from Th1 cell)

C-myc Overexpression - associated with what translocations?

- Seen in many malignancies - The myc oncogene is located on chromosome 8 - Translocations between ch8 and chromosomes coding for the immunoglobulin heavy chain (14), the kappa light chain (2), or the lambda light chain (22) may result in Burkitt Lymphoma

Berkson's bias

- Selection bias created by choosing hospitalized pts as the control group

Fenoldopam

- Short-acting, selective, peripheral dopamine-1 receptor agonist with little/no effect on alpha or beta receptors - D1 receptor stimulation: activates adenylyl cyclase and raises intracellular cAMP --> vasodilation of most arterial beds with decrease in systemic BP - Renal vasodilation --> increased renal perfusion, diuresis and natriuresis - Beneficial in pts with severe hypertension that have acute kidney injury

Patent ductus arteriosus: what are the signs? What keeps it open? What meds can help close it?

- Signs: continuous murmur, tachycardia, widened pulse pressure, and respiratory distress - Production of prostaglandin E2 by the placenta combined with high right-to-left blood flow across the ductus keeps it open - after delivery, separation from the placenta and the rapid drop in pulmonary vascular resistance lead to functional closure of the ductus - Commonly found in preterm infants - If left untreated: can cause pulmonary edema, heart failure, or Eisenmenger syndrome - Many will spontaneously close with time; NSAIDS (indomethacin, ibuprofen) can help close the PDA by inhibiting prostaglandin E2 synthesis

Where do you see intracellular spherical aggregates of tau protein seen on silver stain?

- Silver stain = Pick bodies - Pick's disease: frontotemporal dementia

Teriparatide

- Simulates maturation of pre-osteoblasts into bone-forming osteoblasts that lay down collagen and eventually mineralize the matrix - Increases calcium absorption and renal tubular calcium reabsorption --> decreased urinary calcium excretion

What are the different parts of the spleen and what do they house? What are macrophages function in the spleen?

- Sinusoids are long, vascular channels in red pulp with fenestrated "barrel hoop" basement membrane - T cells are found in the periarteriolar lymphatic sheath (PALS) within the white pulp - B cells are found in the follicles within the white pulp - The marginal zone: inbetween the red pulp and the white pulp contains macrophages and specialized B cells and is where antigen presenting cells capture blood-borne antigens for recognition by lymphocytes - Macrophages found nearby in spleen remove encapsulated bacteria

What structures do you cut through in order to perform a cricothyrotomy?

- Skin - Superficial cervical fascia (including subcutaneous fat and platysma muscle) - Investing and pretracheal layers of the deep cervical fascia - Cricothyroid membrane

snRNPs

- Small nuclear ribonucleoproteins that help to splice out introns from pre-mRNA, forming mature RNA

microRNA

- Small, noncoding RNA molecules that posttranscriptionally regulate protein expression (introns can contain microRNA genes) - miRNA --> degradation or inactivation of target mRNA --> decreases translation into protein

In what viruses is hemadsorption seen in?

- Some influenza and parainfluenza viruses

Hereditary spherocytosis

- Spheroid erythrocytes due to spectrin or ankyrin defect - Hemolytic anemia - Increased MCHC, RDW - Tx: splenectomy

What happens with spleen dysfunction? What organisms are the pts most at risk for?

- Splenic dysfunction (postsplenectomy, sickle cell disease): Decreased IgM --> decreased complement activation --> decreased C3b opsonization --> increased susceptibility to encapsulated organisms - Encapsulated organisms: Pseudomonas, Strep Pneumo, H Flu, Neisseria Meningitidis, E Coli, Salmonella, Klebsiella Pneumo, Group B Strep

Osmium tetroxide stain

- Stains fat black - can be used in lungs to show fat globules that are trapped in and occluding pulmonary microvessels

What is derived from the second pharyngeal arch?

- Stapes, styloid process, stylohyoid ligament, lesser horn of hyoid - M. of facial expression, stapedius, stylohyoid - Facial n

What are the start and stop codons?

- Start: AUG - codes for Methionine - Stop: UGA, UAA, UAG (U Go Away, U Are Away, U Are Gone)

Glycogen in hepatocytes

- Stored and undergoes glycogenolysis to maintain blood sugar at appropriate levels - Glycogen phosphorylase liberates glucose-1-phosphate residues off branched glycogen until 4 glucose units remain on a branch --> then 4-alpha-D-glucanotransferase (debranching enzyme) moves 3 molecules of glucose-1-phosphate from the branch to the linkage --> then alpha-1,6-glucosidase (debranching enzyme( cleaves off the last residue liberating glucose - "Limit Dextran" refers to the one to four residues remaining on a branch after glycogen phosphorylase has already shortened it

Paradoxical embolism - What is it? When does it occur?

- Stroke in the setting of a known venous thromboembolic disease is suspicious for paradoxical embolism - An emboli that originates in the systemic venous circulation and enter the systemic arterial circulation via an intracardiac or intrapulmonary shunt - Occurs in pts with patent foramen ovale, atrial septal defects, ventricular septal defects or large pulmonary arteriovenous malformations

Ecthyma gangrenosum

- Strongly associated with Pseudomonas bacteremia - Bacterial invasion of the arteries and veins in the dermis and subQ tissue with subsequent release of exotoxin --> skin patches exhibiting necrosis and ulceration as a result of insufficient blood flow

Alendronate

- Structurally similar to pyrophosphate - Bisphosphates are preferred initial tx for osteoporosis in most pts due to low cost, efficacy and long-term safety - A bisphosphonate that attaches to hydroxyapatite binding sites on bony surfaces, preferentially binding in areas of increased bone turnover - Osteoclasts that resorb bone take up the bisphosphonate and are unable to adhere to more bony surfaces to continue resorption - Also induces osteoclast apoptosis and decreases development/recruitment of osteoclast precursor cells --> decreased bone loss and stable or increased bone mineral density - Note: take on an empty stomach with plenty of water (due to poor GI absorption) and remain upright for 30 mins (due to possible esophageal erosion)

What is derived from the third pharyngeal arch?

- Stylopharyngeas m - Glossopharyngeal n

What are the 2 primary sources of alkaline secretions that helps protect the small intestinal mucosa?

- Submusocal (Brunner) glands: secrete alkaline mucus into the duodenum. They are most numerous in the pylorus but may be found intermittently up to the ampulla of Vater. The ducts of these glands pass through the muscularis mucosa and terminate in the mucosal crypts - The epithelial cells of the pancreatic ductules and ducts: produce watery secretions containing high concentration of bicarbonate ions. These secretions are then emptied into the duodenum at the ampulla

What meds may cause photosensitivity as a side effect?

- Sulfonamides, Amiodarone, Tetracycline

What are the rotator muscles and what does each one do?

- Supraspinatus M: initiation of abduction - empty can test - Infraspinatus M: lateral rotation at the shoulder - Teres Minor: lateral rotation at the shoulder - Subscapularus M: medial rotation at the shoulder

Causes and symptoms of angioedema

- Swelling of the tongue, lips, or eyelids - Laryngeal edema and difficulty breathing may also occur

What are the 2 mechanisms that a host's immune system provides to fight against Candida Infections?

- T cells: important for prevention of superficial Candida infection (oral/esophageal Candidiasis, cutaneous infections, vulvovaginal infections - Neutrophils: prevent hematogenous spread and Candida and is important in prevention of disseminated candidiasis (candidemia, endocarditis)

How do you calculate total peripheral resistance in the body? (hint: parallel circuits) How do you calculate the resistance of blood flow through an organ? (hint: circuits in series)

- TPR if parallel circuits: 1/Rt = 1/R1 + 1/R2 + 1/R3 +....1/Rn - TPR if circuits in series: Rt = R1 + R2 + ..... Rn - Total resistance in organs = Rartery + Rarteriole + Rcapillary + Rvenule + Rvein (all are in series)

Hawthorne effect

- Tendency of study subjects to change their behavior as a result of their awareness that they are being studied

Normal distribution curve follows what rule for standard deviations?

- The 68/95/99 rule

Aortic arch derivatives

- The Common Carotid A is derived from the third aortic arch

What is a landmark that will best aid a surgeon in distinguishing an indirect from a direct hernia?

- The Inferior Epigastric Vessels

What part of Vit D synthesis is impaired in chronic kidney disease?

- The conversion of 25-hydroxyvitamin D --> 1,25-dihydroxyvitamin D --> decreased levels of active Vit D

What may cause dilation of the coronary sinus?

- The coronary sinus carries most of the venous drainage from the myocardium and delivers deoxygenated blood to the right atrium - It will become dilated by any factor that causes dilation of the right atrium - Most common cause of dilation: elevated right-sided heart pressure secondary to pulmonary hypertension - Can also occur in pts with anomalous venous drainage into the CS, including persistent left superior vena cava and total anomalous pulmonary return

What nerve innervates external hemorrhoids? Internal hemorrhoids?

- The inferior rectal n, a branch of the Pudendal nerve - external - Internal: autonomic innervation from the inferior hypogastric plexus - only sensitive to stretch, not pain, temp or touch

Henoch-Schonlein purpura

- The most common systemic vasculitis in children - Caused by circulating IgA-antigen immune complexes --> deposite in walls of small vessel and renal mesangium --> recruitment of neutrophils and lymphocytes as well as activation of complement via alternate/lectin pathways --> inflammation that leads to organ dysfunction and palpable purpura - Self-limited and resolves as the circulating immune complexes clear - Tx: supportive

What is derived from the notochord?

- The notochord is a mesodermally derived structure that almost completely regresses in humans - Its only major derivative is the nucleus pulposus of the intervertebral disc

IL-10

- The only cytokine with anti-inflammatory properties - Reduces production of pro-inflammatory Th1 cytokines (IL-2 and IFN-gamma) and MHC II expression - Inhibits activated dendritic cells and macrophages - Leads to the attenuation of cellular-mediated immunity with some enhancement of the humoral response --> protective effect in Crohn's disease

After the clavicle is broken, what structure will most likely assist in producing new bone to heal the fracture?

- The periosteum

Placenta accreta

- The placenta is morbidly adherent to the myometrium - scar tissue from prior surgery (such as C Section) can result in malformed or absent decidual layer between the placenta and that myometrium allowing for direct myometrial attachment by the villous tissue and preventing normal placental separation after fetal delivery - Usually dx'ed during prenatal care and managed by C section followed by hysterectomy

What nerves lie within the fascia of the prostate and what would happen if these nerves were damaged in a prostectomy?

- The prostatic plexus: the lesser and greater cavernous nerves arise from the prostatic plexus and pass beneath the pubic arch to innervate the corpora cavernosa of the penis and urethra - carry the post-ganglionic parasympathetic fibers that facilitate penile erection - Damage can lead to erectile dysfunction

Bcr-abl hybrid

- The result of a reciprocal translocation between chromosomes 9 and 22 (Philadelphia chromosome) - Characteristic in Chronic Myelogenous Leukemia (CML)

Where are the 3 leads positioned in a biventricular pacemaker?

- The right atrium, right ventricle, and left ventricle - The left ventricular lead is most difficult to position - the preferred transvenous approach involves passing the left ventricular pacing lead from the right atrium into the coronary sinus, which resides in the atrioventricular groove on the posterior aspect of the heart --> advanced into one of the lateral venous tributaries in order to optimize left ventricular pacing

What structures are most likely to be primarily damaged by chronic rejection of a lung transplant?

- The small bronchioles (bronchiolitis obliterans): inflammation and fibrosis of the bronchiolar walls lead to narrowing and obstruction of the affected bronchioli - Presentation: dyspnea, nonproductive cough, and wheezing

What is the embryologic derivative of the spleen?

- The spleen is derived from condensed mesenchymal tissue in the dorsal mesentery during embryonic development - Mesenchymal tissue arises from the mesoderm germ layer and is characterized by loosely associated cells surrounded by extracellular matrix

How do we repair damage done to DNA due to ionizing radiation (x-rays and gamma rays)?

- These cause double-stranded DNA breaks - the fractures ends can be joined by nonhomologous end joining

How far do the neural crest cells migrate in the bowel?

- They are present in the proximal colon at the 8th week of gestation and migrate all the way to the rectum by the 12th week - Hirschsprung disease always involves the rectum

Function of Vit B1

- Thiamine - Cofactor for several dehydrogenase enzyme reactions: pyruvate dehydrogenase (links glycolysis to TCA cycle), alpha-ketoglutarate dehydrogenase (TCA cycle), Transketolase (HMP shunt), Branched-chain ketoacid dehydrogenase

Why is thiamine important? What neuro structure undergoes necrosis in thiamine deficiency?

- Thiamine is the key coenzyme for pyruvate dehydrogenase which is involved in glucose metabolism - In thiamine deficiency --> brain can't properly metabolize glucose and turn it into energy - Mammillary body - involved in control of emotion and memory

What drugs interact with Lithium that can lead to toxicity?

- Thiazide diuretics, NSAIDs, ACE inhibitors, Tetracyclines, Metronidazole

What is the most common cause of retinal artery occlusion?

- Thromboembolitic complications of atherosclerosis in the internal carotid artery --> ophthalmic artery --> retinal a

How does TNF-alpha induce insulin resistance?

- Through activation of serine kinases --> phosphorylate serine residues on the beta subunits of IR and IRS-1 --> inhibits tyrosine phosphorylation of IRS-1 by IR and subsequently hinders downstream signaling --> resistance of the normal actions of insulin - Substances that use same mechanism to induce insulin resistance: catecholamines, glucocorticoids, and glucagon - Phosphorylation of threonine residues has similar effects

Radiation exposure puts a pt at highest risk for what type of cancer?

- Thyroid cancer - The thyroid gland is one of the most radiation-sensitive parts of the body and radiation exposure is the most important risk factor for primary thyroid malignancy - usually papillary thyroid cancer

Venous stasis dermatitis

- Tissue ischemia that occurs due to incompetence of the venous valves --> allows retrograde flow into superficial veins and increases venous pressure - Extravasion of RBCs into the tissues leads to iron deposition and the characteristic brawny discoloration - Associated with poor wound healing

What is the function of T tubules in a muscle cell membrane?

- To ensure that a depolarizing signal reaches each fiber at the same time to allow for a coordinated contraction

Why would a pt be prescribed a pulsatile dose of GnRH?

- To increase LH and FSH --> ovulation - For infertility due to anovulation

What causes spider angiomas in pts with liver disease?

- Too much estrogen - due to decreased metabolism of estrogen by the failing liver, decreased production of sex hormone binding globulin by the liver, and decrease metabolism of androgens, which are converted peripherally to estrogens by aromatase

Latanoprost

- Topical prostaglandin used in the treatment of glaucoma - Applied as a prodrug and converted to the active form by esterases in the cornea - Decrease the collagen content in the uveoscleral outflow pathway and increase outflow of aqueous humor - Also known to cause increased pigmentation in the iris and eyelashes

Marasmus

- Total calorie malnutrition resulting in emaciation (tissue and mm wasting, loss of subcutaneous fat); +/- edema

Lecithinase

- Toxin A - Produced by C. Perfringens - hydrolyzes lecithin in cell membranes --> cell lysis and development of gas gangrene

What structure can be cut to improve symptoms of carpal tunnel?

- Transverse carpal ligament (flexor retinaculum)

What are the signs and symptoms of ammonia accumulation?

- Tremor (asterixis), slurring of speech, somnolence, vomiting, cerebral edema, blurring of vision

Wernicke encephalopathy

- Triad: ophthalmoplegia, ataxia, and confusion - Foci of hemorrhage and necrosis in the mammillary bodies and periaqueductal gray matter are typically found at autopsy - Due to chronic thiamine deficiency, which is common in pts with alcoholism - If you give IV dextrose in alcoholic pt without first administering thiamine --> acute drop of thiamine --> Wernicke encephalopathy

What is the Ebstein abnormality?

- Tricuspid leaflets are displaced into right ventricle, hypoplastic right ventricle, tricuspid regurgitation or stenosis - 80% have a patent foramen ovale with a right-to-left shunt - Dilated right atrium causing increased risk of SVT and WPW - Physical exam: widely split S2, tricuspid regurgitation - Associated with maternal Lithium use

First pharyngeal arch

- Trigeminal n (CN5) - Maxilla, zygoma, mandible, incus, and malleus - Mm of mastication

Patau syndrome

- Trisomy 13 - Severe ID, rocker bottom feet, microphthalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactyly, congenital heart disease, cutis aplasia - Death usually within a year - First trimester: decreased free beta-hCG, PAPP-A

Edwards Syndrome

- Trisomy 18 - Severe ID, rocker-bottom feet, microagnathia (small jaw), low-set ears, clenched hands with overlapping fingers, prominent occiput, congenital heart disease - Death usually by 1 year - PAPP-A and free beta-HCG are decreased in first trimester - Quad screen: Decreased alpha-fetoprotein, beta-hCG, estriol, decreased or normal inhibin A

Metformin - What is the mechanism of action? When should it be avoided? Why?

- Tx for type 2 diabetes - Inhibits mitochondrial glycerophosphate dehydrogenase and complex I (first electron transport chain enzyme) --> decrease in cellular energy stores causing AMPK activation --> decreased hepatic gluconeogenesis - Also increases peripheral glucose utilization - DOES NOT increase endogenous insulin secretion or cause hypoglycemia - Increases risk of lactic acidosis, especially in pts with hepatic or renal dysfunction - check serum creatinine before initiation - Also avoid in pts with congestive heart failure or alcoholism

Von Gierke Disease

- Type 1 Glycogen storage disease - Findings: severe fasting hyperglycemia, increased glycogen in liver, increased blood lactate, increased triglycerides, increased uric acid (gout), and hepatomegaly - Glucose-6-phosphotase deficiency - Tx: frequent oral glucose/cornstarch, avoidance of fructose and galactose - Impaired gluconeogenesis and glycogenolysis

What type of hypersensitivity reaction are erythroblastosis fetalis and hemolytic disease of the newborn?

- Type 2 - Caused by anti-fetal erythrocyte antibodies (IgG) that crosses placenta and leads to erythrocyte destruction

Pompe Disease

- Type 2 glycogen storage disease - Findings: cardiomegaly, hypertrophic cardiomyopathy, exercise intolerance, and systemic findings --> early death - Deficient in lysosomal alpha-1,4-glucosidase with alpha-1,6-glucosidase activity (acid maltase) - "Pompe trashes the Pump"

Cori Disease

- Type 3 glycogen storage disease - Milder form of von Gierke with normal blood lactate levels - Accumulation of limit dextran-like structures in the cytosol - Deficiency in the debranching enzyme (alpha-1,6-glucosidase) - Gluconeogenesis is in tact

McArdle Disease

- Type 4 glycogen storage disease - Increased glycogen in muscle, but muscle cannot break it down --> painful muscle cramps, myoglobinuria (red urine) with strenuous exercise, and arrythmia from electrolyte abnormalities - Second wind phenomenon noted during exercise due to increased muscular blood flow - Deficiency in skeletal mm glycogen phosphorylase (myophosphorylase) - Blood glucose levels typically unaffected - McArdle = Muscle)

Amyloidosis in the kidney

- Type of nephrotic syndrome - Amyloid obliterates the capillaries - Pink stained with Congo Red, apple-green birefringence under polarized light - Leads to end stage renal disease - reaching nephrotic syndrome is poor prognosis

Diabetic nephropathy

- Type of nephrotic syndrome - Nonenzymatic glycosylation --> thickening of basement membrane --> nodular sclerosis - LM: Kimmelsteil-Wilson nodules - pink round deposits of laminated mesangial matrix; also see sclerosis - obliterated capillaries with hyalin deposition

Lactate dehydrogenase deficiency

- Typically NAD+ is regenerated from NADH when pyruvate is converted to lactate (via lactate dehydrogenase) during anaerobic glycolysis - In LD Def: clycolysis is inhibited in strenuously exercising muscle as the muscle cells cannot regenerate NAD+ --> high-intensity physical activity leads to muscle breakdown, pain, and fatigue as insufficient amounts of energy are being produced in the exercising muscle - Pyruvate will accumulate in the cell under anaerobic conditions

Lung abscess

- Typically find bacteria that are part of the normal mouth flora - Peptostreptococcus and Fusobacterium - As the abscess evolves, it typically forms a cavitary lesion with an identifiable air-fluid level on imaging - Symptoms: fever, night sweats, weight loss, and cough production of foul-smelling sputum (indicative of anaerobes)

Atheroembolic renal disease

- Typically occurs after manipulation of the aorta (abdominal aortic aneurysm repair) in adults with widespread atherosclerosis - Atheroemboli with cholesterol clefts are seen within the arterial lumen

Eisenmenger syndrome

- Uncorrected left-to-right shunt (VSD, ASD, PDA) --> increased pulmonary blood flow --> pathologic remodeling of vasculature --> pulmonary arterial hypertension - RVH occurs to compensate --> shunt becomes right-to-left - Late cyanosis, clubbing of fingers, and polycythemia

Glycogen in skeletal mm

- Undergoes glycogenolysis --> glucose-1-phosphate --> glucose-6-phosphate which is rapidly metabolized during exercise

Hep E

- Unenveloped, single-stranded RNA virus spread through fecal-oral route - Occurs primarily in young and middle-aged adults in Asia, sub-Saharan Africa, and Mexico - Avg incubation: 6 weeks - Has a high mortality rate in infected pregnant women (about 20%)

What are the signs of an intracranial schwannoma? Where is it typically located?

- Unilateral hearing loss with facial numbness and weakness - Most commonly located at the cerebellopontine angle - between the cerebellum and the lateral pons ("acoustic schwannomas")

Transformation

- Uptake of naked DNA by a prokaryotic or eukaryotic cell - In virology, also describes the incorporation of viral DNA into a host cell chromosome - Alters the genetic composition of the host cell but typically causes no genomic change in progeny virions

How do natural killer cells induce apoptosis?

- Use perforin and granzymes to induce apoptosis of virally infected cells and tumor cells - Induced to kill when exposed to a nonspecific activation signal on target cell and/or an absence of class 1 MHC on target cell surface - Also kills via antibody-dependent cell-mediated cytotoxicity (CD16 binds Fc region of bound Ig, activating NK cell)

Risks of taking prenatal Lithium

- Used for bipolar disorder - Increased incidence of Ebstein Anomoly: atrial septal defect, atrialized right ventricle, malformed tricuspid valve

Risks of taking prenatal Valproate

- Used for bipolar disorder or epilepsy - Associated with a 10-20-fold increased risk of neural tube defects due to impaired folate metabolism - Similar risk factors include the use of folate antagonists, such as methotrexate or TMP-SMX

Methacholine

- Used for bronchoprovocation to test for asthma in pts with normal pulmonary function tests; histamine administration, exercise, or cold air inhalation may also work - Muscarinic cholinergic agonist that causes bronchoconstriction and increased airway secretions - A decreased in FEV1 after methacholine challenge indicates bronchial asthma

Pralidoxime

- Used in organophosphate poisoning - Reverses effects of both muscarinic and nicotinic overstimulation by regenerating AChE in the neuromuscular junction

Tzanck Smear

- Used to dx herpes simplex or varicella zoster virus infection - Epithelial cells are scraped from the ulcer base and are prepared with a Wright-Giemsa stain and examined for multinucleated giant cells and intranuclear inclusions

Papanicolaou test

- Used to screen cervical cytology specimens for dysplasia caused by HPV

How does Ganciclovir work?

- Used to tx CMV - Inhibits DNA chain elongation by both incorporating into viral DNA and inhibiting viral DNA polymerase

Ribavirin

- Used to tx chronic Hep C infection (antiviral) and RSV - Nucleoside antimetabolite drug that interferes with duplication of viral genetic material

Albendazole

- Used to tx tapeworm (cestode) Echinococcus granulosus - which produces cysts in the liver and body

What is the translocation in Burkitt lymphoma?

- Usually a translocation between the c-Myc oncogene on the long arm of chromosome 8 and the Ig heavy chain region on chromosome 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

Popliteal cysts

- Usually caused by swelling of the gastrocnemius or semimembranous bursa - Form due to extrusion of synovial fluid from the knee joint into the bursa in patients with osteoarthritis or inflammatory joint disease

Neonatal tetanus - Clinical features, treatment, prevention (chart)

- Usually caused by unhygienic deliveries or cord care - Prevention: vaccinate women who are pregnant or may become pregnant with the inactivated tetanus toxin - Tetanus vaccination is not given at birth because the neonatal immune system is immature and unable to mount a proper memory immune response against the toxin -- Can be given no earlier than 4-6 weeks of age

What might cause constipation, new-onset second degree AV block, and syncope in the setting of new medication use for A fib?

- Usually due to Ca2+ Channel blocker (Diltiazem and Verapamil)

Damage to the anatomical snuffbox

- Usually due to scaphoid fractures: most common carpal bone fractures - Frequently result from fall onto an outstretched hand that cause direct axial compression or wrist hyperextension - Major concern: avascular necrosis and nonunion

Fetal hydronephrosis

- Usually insignificant as the fetal renal pelvis has high compliance and can accommodate large volumes of urine - this compliance makes the fetal kidney sisceptible to dilation (hydronephrosis), particularly in the setting of obstruction - The most common cause of unilateral fetal hydronephrosis is a narrowing or kinking of the proximal ureter at the ureteropelvic junction - Newborns: may present with a palpable abdominal mass reflecting an enlarged kidney

What is the most common bacteria that causes appendicitis and abdominal abscesses?

- Usually they are polymicrobial - Bacteroides fragilis is a common anaerobic gram-negative bacillus that is frequently isolated in these infections - It expresses unique surface polysaccharides that have been shown to favor abscess formation - E Coli, enterococci, and streptococci are also common

What is the most common cause of postpartum hemorrhage?

- Uterine atony: failure of the uterus to contract adequately after delivery

Compression of the left renal vein between the aorta and the superior mesenteric artery can lead to what? Why?

- Varicocele - The left gonadal vein empties into the left renal artery - this does not occur on the right side as the right gonadal vein empties directly into the IVC

Vascular type Ehlers-Danlos syndrome

- Vascular and organ rupture - Due to deficiency in type 3 collagen

What drives angiogenesis (blood vessel formation) and is prevalent in highly vascularized tumors?

- Vascular endothelial growth factor: increases endothelial cell motility and proliferation and allows for new capillaries to sprout - Fibroblast growth factor: involved in endothelial cell proliferation, migration, and differentiation; also plays an important role in embryogenesis by stimulating angioblast production - contribute to angiogenesis, embryonic development, hematopoiesis, and wound repair

What are the 4 pharmacokinetics equations that are most important for the STEP?

- Vd = D/C (Amount of drug in IV/Concentration in the plasma) - Clearance = rate of elimination/[plasma] = (.7xVd)/t1/2 - Loading dose = [steady state]xVd - Maintenance dose = [steady state]xClearance

What are the 3 major apertures in the diaphragm and which structures pass through each?

- Vena caval foramen (T8): Inferior vena cava, terminal branches of the right phrenic nerve (left phrenic n passes through a small opening of its own) - Aortic hiatus (T12): Aorta, Thoracic duct, Azygos vein - Esophageal hiatus (T10): esophagus and anterior and posterior trunks of the vagus nerve

Describe the venous drainage from the rectum - what does this mean for cancer metastasis?

- Venous drainage of rectum above the dentate line occurs through the superior rectal vein which drains into the portal venous system via the inferior mesenteric vein - cancers of the proximal rectum often metastasize to the liver - Structures below the dentate line drain into the middle and inferior rectal veins, which drain into systemic circulation via the internal iliac vein - Cancers of the distal rectum often metastasize to the lungs

How does anaphylaxis affect cardiac output and venous return?

- Venous return is decreased as there is widespread venous and arteriolar dilation along with increased capillary permeability - Cardiac contractility increases as the body attempts to maintain blood pressure

What are the 4 main defects in Tetralogy of Fallot? What is the major determinate of the severity of the condition?

- Ventricular septal defect, overriding aorta, right ventricular outflow obstruction, and right ventricular hypertrophy - RVOT obstruction determines how much deoxygenated blood is delivered to the systemic circulation and determines severity of symptoms - is dynamic and can increase suddenly

How does E Coli acquire the ability to form pili?

- Via bacterial conjugation - genes for antibiotic resistance are also conferred via this mechanism

How does C. Diphtheriae acquire its virulence?

- Via bacteriophage-mediated "infection" with the Tox gene that codes for the diphtheria AB exotoxin

How does Strep pneumo acquire its ability to produce capsules?

- Via transformation

Wernicke-Korsakoff Syndrome - Damage is to what parts of the brain?

- Vit B1 (Thiamine) def - Confusion, opthalmoplegia, ataxia (classic triad); confabulation, personality change, memory loss (permanent) - Damage to medial dorsal nucleus of the thalamus, mammilary bodies

Dry Beriberi

- Vit B1 (thiamine) def - Polyneuritis, symmetrical mm wasting

Wet Beriberi

- Vit B1 (thiamine) def - high-output cardiac failure (dilated cardiomyopathy), edema

Pallagra

- Vit B3 (niacin) def - Diarrhea, Dementia (with hallucinations), and Dermatitis - Dermatitis: C3/C4 dermatome circumferential "broad collar" rash; hyperpigmentations of sun-exposed limbs

scurvy

- Vit C deficiency, usually seen in severely malnourished pts (homeless, alcohol, drug abusers) - Easy bruising, mucosal bleeding, and perifollicular petechial hemorrhages, periodontal disease, poor wound healing, and hyperkeratotic follicles with corkscrew hairs - Unable to hydroxylize proline and lysine residues of collagen --> cross-linking is compromised and tensile strength is decreased

Normal pressure hydrocephalus

- Wet, wobbly, wacky - Potentially reversible dementia, urinary incontinence, gait disturbance

When can an alcoholic develop Wernicke encephalopathy in the hospital?

- When an alcoholic pt with low levels of baseline thiamine is given IV dextrose without prior thiamine supplementation --> acute drop in thiamine level --> Wernicke encephalopathy - Ataxia, nystagmus, ophthalmoplegia, anterograde amnesia

When might pigment gallstones occur in the absence of infection?

- When excess bilirubin is excreted, such as with chronic hemolytic anemia - A small amount of conjugated bilirubin normally becomes deconjugated by endogenous beta-glucuronidase in the biliary tract, when large amounts of conjugated bilirubin are excreted into the bile, enough becomes deconjugated to promote black pigment stone formation

Becker muscular dystrophy

- X-linked - Due to non-frameshift insertions in the dystrophin gene (partially functional instead of truncated) - Less severe than Duchenne; onset in adolescence or early adulthood

G6PD def (clinical manifestations)

- X-linked - Most common human enzyme def - more common among African Americans - increases malarial resistance - Heinz bodies: denatured hemoglobin precipitates within RBCs due to oxidative stress - only seen with methylene blue stain - Bite cells: results from phagocytic removal of Heinz bodies by splenic macrophages

Duchenne muscular dystrophy

- X-linked disorder - Due to frameshift or nonsense mutations --> truncated dystrophin protein --> inhibited muscle regeneration - Weakness begins in pelvic muscles, pseudohypertrophy of calf muscles due to fibrofatty replacement of muscle - Gower maneuver: use arms to stand - Dilated cardiomyopathy is common cause of death - Increased CK and aldolase are seen

Menkes Disease

- X-linked recessive - Connective tissue disease caused by impaired copper absorption and transport due to defective Menkes protein (ATP7A) - Leads to decreased activity of lysyl oxidase (copper is a necessary cofactor) - Results in brittle, kinky hair, growth retardation, and hypotonia

G6PD Deficiency - inheritance pattern; Why is G6PD necessary?

- X-linked; most common in African, Asian and Mediterranean descent - G6PD is needed to maintain NADPH in RBCs - insufficient NADPH --> inability to maintain glutathione in the reduced state --> increases vulnerability of RBCs to oxidative stress and manifests with hemolysis induced by infection, drugs, and other oxidants

What hormone is most likely released from a testicular tumor that is producing symptoms of hyperthyroidism? Why?

- hCG: has same alpha unit and similar beta unit as TSH and is able to bind to the TSH receptors --> increased T3 and T4 --> paraneoplastic hyperthyroidism

Fomepizole

- inhibits alcohol dehydrogenase - Antidote for methanol or ethylene glycol poisoning

What tests are used to measure fetal lung maturity? (4)

- lecithin:sphingomyelin ratio (>2 indicates maturity), measurement of surfactant/albumin ratio, the slide agglutination test for phosphatidylglycerol, and the foam stability test

How do the tumor suppressors p53 and Rb work?

- p53 induces p21, which inhibits CDKs --> hypophosphorylation (activation) of Rb --> Rb binds to and inactivates transcription factor E2F --> inhibits cell cycle progression of G1-S phase - Mutations in above lead to unrestricted cell division - Li-Fraumeni syndrome

What is the translocation in Mantle cell lymphoma?

- t(11;14): Activation of Cyclin D1 --> very aggressive and pts typically present in late stage

What is the translocation in Follicular lymphoma? What are the symptoms?

- t(14;18): Bcl-2 activation - inhibits apoptosis - Painless waxing and waning of lymphadenopathy

What is the translocation in CML?

- t(9;22): Bcr-Abl - constitutively active tyrosine kinase - Responds to bcr-abl tyrosine kinase inhibitors (Imatinib)

Naive T cell activation

1. Dendritic cell (specialized APC) samples and processes antigen 2. Dendritic cell migrates to the draining lymph node 3. T-cell activation (signal 1): antigen is presented on MHC II and recognized by TCR on Th (CD4+) cell; endogenous antigens are presented on MHC I to Tc (CD8+) cell 4. Proliferation and survival (signal 2): costimulatory signal via interaction of B7 proteins (CD80/86) and CD28 5. Th cell activates and produces cytokines; Tc cell activates and is able to recognize and kill virus-infected cell

Tx of an acute C. diphtheriae infection (in order of importance)

1. Diphtheria antitoxin (passive immunity) 2. Penicillin or erythromycin 3. DPT vaccine

Generation of antibody diversity (antigen independent)

1. Random recombination of VJ (light-chain) or V(D)J (heavy chain) genes 2. Random addition of nucleotides to DNA during recombination by terminal deoxynucleotidyl transferase (TdT) 3. Random combination of heavy chains with light chains

B-cell activation and class switching

1. Th-cell is activated 2. B-cell receptor-mediated endocytosis; foreign antigen is presented on MHC II and recognized by TCR on Th cell 3. CD40 receptor on B cell binds CD40L on Th cell 4. Th cell secretes cytokines that determine Ig class switching of B cell. B cell activates and undergoes class switching, affinity maturation, and antibody production

Types of Homocystinuria

3 Different Types: - Cystathionine synthase def: tx - decrease methionine, increase cysteine, increase B12 and folate in diet - Decreased affinity of cystathionine synthase for pyridoxal phosphate (tx - increase B6 and cysteine in diet) - Methionine synthase (homocysteine methyltransferase) def (tx - increase methionine in diet)

Generation of antibody specificity (antigen dependent)

4. Somatic hypermutation and affinity maturation (variable region) 5. Isotype switching (constant region) - Steps 1-3 are on card "Generation of antibody diversity"

What are the nuclear localization signals?

A sequence of 4-8 amino acids rich in Proline, Arginine and Lysine, these are more positive charged (To get into the club you must be PALs with the bouncer)

What meds are used to tx CHF that improve survival rate?

ACE inhibitors, ARBs, Aldosterone antagonists, Certain beta-blockers (metoprolol, carvedilol, bisoprolol)

What meds may cause cough as a side effect? Why?

ACE inhibitors: due to increased bradykinin

When might you hear a fixed S2 split?

ASD

What cellular by-products might you detect in the serum when hepatocytes are injured?

AST, ALT, alkaline phosphatase, GGT

What sequences are prevalent in promoter regions and origins of replication?

AT rich segments (promoter - TATA and CAAT boxes)

What is the pathophysiology behind preeclampsia?

Abnormal placental vasculature --> placental hypoxia and ischemia --> release of antiangiogenic factors into maternal circulation --> endothelial injury --> increased permeability and proteinuria

What is the first line therapy for idiopathic intracranial hypertension?

Acetazolamide: slows down the formation of CSF - Retinoic acid can cause idiopathic intracranial htn

What innervates the carotid sinus? Afferent and Efferent limbs?

Afferent: Glossopharyngeal n (CN9) Efferent: Vagus n (CN10) - The vagus n acts as afferent limb for the nerve fibers originating from the aortic arch baroreceptors and efferent limb for carotid sinus

What is the most common preventable cause of congenital malformations in the US?

Alcohol use during pregnancy

What is the medical treatment for pheochromocytoma?

Alpha antagonists: Phenoxybutamine, Phantolamine

What do you see extracellular amyloid deposits in the gray matter as well as intracellular deposits of hyperphosphorylated tau protein?

Alzheimer's

What is the most common cause of dementia?

Alzheimer's

What meds may cause nephrotox and neurotox as side effects?

Aminoglycosides, Cisplatin, Polymixins

What meds may cause nephrotox and ototox as side effects?

Aminoglycosides, Vancomycin, Loop diuretics, Cisplatin

What meds may cause pulmonary fibrosis as a side effect?

Amiodarone, Bleomycin, Busulfan

What meds may cause hypothyroidism as a side effect?

Amiodarone, Lithium, Sulfonamides

What 3 substances stimulate the release of norepinephrine from the presynaptic nerve terminal?

Amphetamines, Ephedrine, Tyramine

What cellular by-products might you detect in the serum if salivary gland cells are injured?

Amylase

What cellular by-products might you detect in the serum if pancreatic exocrine cells are injured?

Amylase, lipase

Citalopram

An SSRI: first line treatments for many mental health disorders (depression, GAD, etc)

What might cause bounding pulses, head bobbing, and a diastolic murmur?

Aortic regurg

When might you hear paradoxical S2 splitting?

Aortic stenosis, left bundle branch block; improves with inspiration

What disorders have mutations in non homologous end joining?

Ataxia telangiectasia and Fanconi anemia

In what organs are each adrenergic receptors located and what are their affect? (chart)

Beta-2: peripheral vasculature (dilation), bronchi (dilation), uterus (relaxation) Alpha-1: peripheral vasculature (constriction), bladder, eye

What are the teratogenic effects of Warfarin?

Bone/cartilage defects (esp in epiphysis), nasal hypoplasia; Heparin is safe during pregnancy

What meds may cause seizures as a side effect?

Buproprion, Imipenem/cilastatin, Isonaizid, Tramadol, Metoclopramide, Benzo/alcohol withdrawal

What cellular by-products might you detect in the serum when skeletal muscles are injured?

CK, aldolase, myoglobin (toxic to kidneys --> renal failure)

How can maternal iodine def affect fetus?

Can lead to congenital hypothyroidism (cretinism)

What is the Fick Principle?

Cardiac Output = rate of O2 consumption/(arterial O2 - venous O2)

What are the teratogenic effects of Flouroquinolones?

Cartilage damage

What meds can cause aplastic anemia as a side effect?

Chloramphenicol, Benzene, NSAIDs, Propylthiouracil, Methimazole

What med causes grey baby syndrome?

Chloramphenicol: due to accumulation of metabolites

What are the teratogenic effects of Diethylstilbestrol (DES)?

Clear cell vaginal adenocarcinoma

What meds can cause agranulocytosis as a side effect?

Clozapine, Carbamazepine, Colchicine, Propylthiouracil, Methimazole, Dapsone

What causes rib notching?

Coarctation of the aorta

What meds cause coronary vasospasm as a side effect?

Cocaine, Amphetamines, Triptans, Ergotamine

What inhibits the reuptake of norepinephrine so that it lasts longer in the nerve terminal?

Cocaine, TCAs, SNRIs

What parts of the kidney are derived from the ureteric bud?

Collecting system - collecting tubules and ducts, major and minor calyces, renal pelvis, and ureters

What meds may cause osteoporosis as a side effect?

Corticosteroids, Heparin

What toxicity can nitroprusside infusion lead to? What is the presentation? What are the tx?

Cyanide toxicity - Presentation: altered mental status, seizures, cardiovascular collapse, lactic acidosis, and bright venous blood - Tx: usually metabolized by rhodanese, an enxyme that transfers a sulfur molecule to cyanide to form thiocyanate - sodium thiosulfate works as an antidote by providing additional sulfur groups for rhodanese, enhancing cyanide detox - used in conjunction with hydroxocobalamin and sodium nitrite - Sodium nitrite: promotes methemoglobin formation which combines with cyanide to form cyanmethemoglobin - Hydroxocobalamin: Cobalt moiety binds to intracellular cyanide ions and forms cyanocobalamin, which is excreted in the urine

What meds may cause hemorrhagic cystitis as a side effect?

Cyclophosphamide, Ifosfamide

What is the mechanism of most alkylating agents used in cancer treatments?

DNA cross-linking

When can you hear an S3 heart sound?

Dilated cardiomyopathy, CHF, Mitral regurg, left --> right shunt

What are the teratogenic effects of Tetracyclines?

Discolored teeth

What meds may cause gout as a side effect?

Diuretics (loop and thiazide), Niacin, Cyclosporine, Pyrazinamide

What meds are used to tx the symptoms of CHF, but do not improve survival rate?

Diuretics, Digoxin, Vasodilators

What meds cause dilated cardiomyopathy as a side effect?

Doxorubicin, Daunorubicin

What are the teratogenic effects of Lithium?

Ebstein anomaly

Dandy Walker Syndrome

Enlarged posterior fossa, cerebellar vermis fails to develop --> dilation of the 4th ventricle - Associated with hydrocephalus and spina bifida

When do you have a lucid interval following a head trauma?

Epidural hematoma

What is derived from the second pharyngeal pouch?

Epithelial lining of the tonsils

What are the teratogenic effects of Phenytoin?

Fetal hydantoin syndrome

What is the most common cause of neural tube defects?

Folate deficiency

What amino acids are required for purine synthesis?

Glycine, Aspartate, and Glutamine ("GAG")

What substances are P450 inducers?

Griseofulvin, Carbamazepine, Phenytoin, Barbiturates, Rifampin, St John's Wort, Chronic alcoholism

What 2 substances inhibit the release of norepinephrine from the presynaptic nerve terminal?

Guanethidine, Bretylium

In pregnant pt with chronic Hep B, the presence of which marker is most likely to increase the risk of vertical transmission of the virus?

HBeAg: a soluble protein that is a marker of viral replication and increased infectivity

What meds may cause hepatic necrosis as a side effect?

Halothane, Acetaminophen, Valproic acid, Amanita phalloides

What cellular by-products might you detect in the serum if RBCs are injured?

Heme --> bilirubin

What meds can cause thrombocytopenia as a side effect?

Herparin (HIT), Cimetidine (H2 blocker)

When may you hear an S4 heart sound?

High pressure stiffened LV wall, hypertrophic cardiomyopathy, aortic stenosis, chronic HTN with LV hypertrophy, post-MI

What is the tx of choice for Torsades de Pointes?

IV Magnesium

Where do you perform a Lumbar Puncture?

In the subarachnoid space between spinal segments L3 & L4 or L4 & L5

How do thiazide diuretics affect Ca2+ resorption?

Increases Ca2+ reabsorption and decreases urinary excretion (prevent calcium stones) in 2 ways: - Inhibits the Na+/Cl- cotransporter on the apical side of the distal convoluted tubule which decreases intracellular Na+ concentrations --> activates the basolateral Na+/Ca2+ antiporter which pumps Na+ into the cell in exchange for Ca2+ --> decreased intracellular Ca2+ concentration which enhances Ca2+ reabsorption across the apical membrane - Hypovolemia induced by thiazide diuretics increases Na+ and H2O reabsorption in the proximal tubule, leading to a passive increase in paracellular Ca2+ reabsorption

What are common conditions that cause left axis deviation?

Inferior wall MI, left anterior fascicular block, left ventricular hypertrophy, left bundle branch block

Vesamichol

Inhibits choline acetyltransferase which packaged choline within the presynaptic nerve cell

Ouabain

Inhibits the Na+/K+ pump by binding to the K+ site

Reserpine

Inhibits the packaging of norepinephrine

Hemicholinium

Inhibits the transport of choline back into the presynaptic nerve cell (via Na+-Choline transporter)

Metyrosine

Inhibits tyrosine hydroxylase , which normally converts tyrosine to DOPA

What are the teratogenic effects of Statins?

Interfere with cholesterol synthesis --> CNS and limb abnormalities

What are the teratogenic effects of Methotrexate?

Interferes with folate metabolism --> neural tube defects, abortion

Observer bias

Investigators misclassify data due to preconceived expectations or prior knowledge concerning the study or its participants - important when outcomes are subjective

What med may cause hapatitis as a side effect?

Isonaizid

What meds cause hemolysis in G6PD deficient pts?

Isoniazid, Sulfonamides, Primaquine, Aspirin (high dose), Ibuprofen, Nitrofurantoin, Dapsone, Fava beans, Naphthalene

What meds may cause diabetes insipidus as a side effect?

Lithium, Demeclocycline

What causes hypercalcemia in a pt with multiple myeloma?

Local IL-1 and TNF effects

What amino acids are histones rich in?

Lysine and arginine - Negatively charged DNA wraps around positively charged histones

What artery supplies the macula of the eye?

MCA

What is the pathway of the CSF?

Made by the choroid plexus --> 2 lateral ventricles --> 3rd ventricle --> cerebral aqueduct --> 4th ventricle --> foramen magenda --> subarachnoid space

Vitamin A's teratogenic effects

May cause spontaneous abortion, cleft palate, and cardiac abnormalities - a neg pregnancy test and two forms of contraception are required while taking isotretinoin

What structures can be damaged in a posterior hip dislocation?

Medial and Lateral Circumflex aa, Fenoral V, Sciatic N, Head of the femur

What meds may cause Parkinson-like syndrome as a side effect?

Metochlopimide, Antipsychotics, Reserpine

What meds may cause a disulfiram-like reaction as a side effect?

Metronidazole, Certain cephalosporins, Procarbazine, First-generation sulfonylureas, Disulfiram

What is derived from the first pharyngeal pouch?

Middle ear cavity, eustachian tubes

Anti-U1 RNP antibodies are highly associated with what disease?

Mixed connective tissue disease (MCTD)

In what condition might the thymus be enlarged?

Myasthenia Gravis

What cellular by-products might you detect in the serum when cardiac myocytes are injured?

Myoglobin, CK, CK-MB, troponin 1

What meds may cause interstitial nephritis as a side effect?

NSAIDs, Furosemide, Antibiotics

What are the teratogenic effects of Carbamazepine?

Neural tube defects

What are the teratogenic effects of Valproic acid?

Neural tube defects

What are bilateral acoustic neuromas associated with?

Neurofibromatosis type 2

Why do those with osteogenesis imperfecta have teeth problems?

Opalescent teeth that wear easily due to lack of dentin

What are the teratogenic effects of Aminoglycosides?

Ototoxicity, CN8 failure

What causes a continuous machine-like murmur?

PDA

Defects in the ubiquitin-poteasome system have been implicated in what disease?

Parkinson's disease

What is most likely cut during a midline episiotomy?

Perineal body

What meds may cause gingival hyperplasia as a side effect?

Phenytoin, Verapamil

What are the teratogenic effects of Thalidomide?

Phocomelia - hypoplasia of the arms and legs

Formula for calculating physiologic dead space

Physiologic dead space = tidal volume X ([PaCO2 - PeCO2]/PaCO2) - PaCO2: arterial partial pressure of CO2 - PeCO2: partial pressure of CO2 in the expired air

What meds may cause Torsades de Pointes?

Potassium channel blockers, Sodium channel blockers, Macrolides, Haloperidol, Chloroquine (antimalarial med), Protease inhibitors

Heteroplasmy

Presence of both normal and mutated mitochondrial DNA --> variable expression of mitochondrially inherited diseases

Histone acetylation

Relaxes DNA coiling, allowing for transcription to take place

What teratogenic effect do ACE inhibitors and ARBs have?

Renal failure, oligohydramnios

What is the most common cause of mitral stenosis?

Rheumatic carditis

What are some common conditions that cause right axis deviation?

Right ventricular hypertrophy, acute right heart strain (massive PE),

What is the most common cause of epidural hematoma?

Rupture of the Middle Meningeal A. (trauma to the side of the head - damage to temporal bone)

What is the most common cause of subdural hematoma?

Rupture of the bridging veins

What is the "Worst headache of my life"?

Ruptured berry aneurysm --> subarachnoid hemorrhage

Antibodies to spliceosomal snRNPs are highly specific for what disease?

SLE

What meds may cause gynecomastia as a side effect?

Spironolactone, Digoxin, Estrogens, Cimetidine, Alcohol (chronic use), Ketoconazole, Marijuana

When do you get bloody CSF on LP?

Subarachnoid hemorrhage

Crossover study

Subjects are randomly allocated to a sequence of 2+ treatments and treatments are switched throughout the trial - allowing pts to serve as their own controls - Must have a washout phase to reduce effects of one treatment leaking into the portion of the trial where the other treatment is being given

What kind of symptoms will you have with detruser hyperactivity?

Sudden, overwhelming urge to urinate - Urge urinary incontinence

What meds may cause a drug induced lupus as a side effect?

Sulfonamides, Hydralazine, Isonaizid, Procainamide, Phenytoin

What is derived from the fourth pharyngeal pouch?

Superior parathyroid glands

What is a selective alpha1-antagonist that is used to tx BPH?

Tamsulosin: selective for alpha1A,D which are only senn in the prostate - does not affect BP

What is the most common congenital cause of early cyanosis?

Tetralogy of Fallot

What parts of the kidney are derived from the metanephric blastema?

The glomeruli, Bowman's space, proximal tubules, the loop of Henle, and the distal convoluted tubules

Explain the development of the lip and palate

The lip and palate form during the fifth-sixth week of embryonic development through a series of fusions: - The first pharyngeal arch splits into the upper maxillary prominence and the lower mandibular prominence - Fusion of the 2 medial nasal prominences forms the midline intermaxillary segment - this will become the philtrum of the upper lip, the 4 medial maxillary teeth and the primary palate - The left and right maxillary prominences then fuse with the midline intermaxillary segment to form the upper lip and primary palate - if one of the maxillary prominences fails to fuse with the intermaxillary segment, a unilateral cleft lip results, if both fails to fuse --> bilateral cleft lip

What is derived from the third pharyngeal pouch?

Thymus and inferior parathyroid glands

What is the most common congenital cardiac anomaly?

VSD

What drugs cause flushing as a side effect?

Vancomycin (Red man syndrome), Niacin, Adenosine, Dihydropyridine calcium channel blockers

What is the second most common cause of dementia?

Vascular dementia

What pancreatic structure is derived from the ventral pancreatic bud? Dorsal bud?

Ventral: The main pancreatic duct, uncinate process, and a portion of the pancretic head Dorsal: pancreatic tail, body, most of the head, and the small accessory pancreatic duct

What are the teratogenic effects of Isoretinoin?

Vitamin A derivative - spontaneous abortions and birth defects Excess Vitamin A can cause microcephaly, cardiac defects and can interfere with neural crest cell migration or HOX gene expression

Interference

When one virus inhibits replication and/or release of a second virus that is infecting the same cell

What are the teratogenic effects of Cyclophosphamide?

ear/facial anomalies, limb hypoplasia, absence of digits