High Yield to Review - AS

++++++++++++ Be Sure to Know This ++++++++++++ When it says "WBC count is ..." and there's no WBC count in the labs, what do you look at? What is the normal WBC count?

LEUKOCYTE count - Leuko = White - Cyte = Cell 4,500 - 11,000 / mm3

Name the encapsulated organisms (Even Serial Killers Have Some Pretty Nice Capsules)

(Even Serial Killers Have Some Pretty Nice Capsules): E. coli Streptococcus pneumoniae Klebsiella pneumoniae H. influenzae Salmonella Pseudomonas aeruginosa Neisseria meningitidis Cryptococcus neoformans (also Group B Strep) or (Please SHiNE SKiS) - First Aid Pseudomonas aeruginosa Streptococcus pneumoniae H. influenzae Neisseria meningitidis E. coli Salmonella Klebsiella pneumoniae Group B Streptococci (neonates) Increased Risk with: Splenectomy Lack of B-cells (also inc. risk for viruses: Enteroviral encephalitis, poliovirus - vaccine c/i)

++++++++++++++++++++++++++++++ ​​​​​​​A 20-year-old woman is brought to the emergency department due to intractable vomiting and abdominal pain. She has a several-week history of anorexia and weight loss. The patient has well-controlled primary hypothyroidism treated with levothyroxine but has not taken her medication for 2 days because of vomiting. Temperature is 37.6 C (99.7 F), blood pressure is 80/40 mm Hg, pulse is 120/min, and respirations are 18/min. On physical examination, she is mildly lethargic but oriented. Generalized hyperpigmentation is present and is most conspicuous over the face, neck, and dorsal surface of the hands. Urinalysis and chest x-ray are within normal limits. Finger-stick blood glucose is 60 mg/dL. A 1-L bolus of normal saline is rapidly infused, and high-flow intravenous fluids are continued. 1. Name the underlying and current diagnosis. 2. This patient also requires immediate treatment with what type of medication? (Note -- like a fifth level question)

- Addison's Disease (currently) and Hashimoto Thyroiditis (hypothyroidism; chronically) - Corticosteroids (Dexmethasone) NEED TO KNOW that a patient with an autoimmune disease is likely to develop or have other autoimmune diseases. - This patient has hypothyroidism. The most common cause of hypothyroidism is Hashimoto's which is an autoimmune disease. This patient most likely has acute adrenal crisis. Her history of hypothyroidism puts her at increased risk for other autoimmune endocrinopathies (eg, autoimmune adrenalitis), and her weight loss and hyperpigmentation are suggestive of chronic primary adrenal insufficiency (Addison disease). In normal individuals, the adrenal glands respond to acute stress (eg, illness, surgery) with a compensatory increase in glucocorticoid production, but patients with adrenal insufficiency cannot mount such a response. Adrenal crisis is characterized by severe hypotension and refractory shock. Associated symptoms include abdominal pain, vomiting, weakness, and fever. In addition to aggressive fluid resuscitation, treatment of adrenal crisis requires immediate glucocorticoid supplementation with hydrocortisone or dexamethasone. Treatment should begin immediately without waiting for results of diagnostic studies, and the response is usually rapid. ^ One of our professors said that if a person has Addison's, dive them steroids RIGHT AWAY or they might die on your table. From previous question: PAI most commonly results from autoimmune destruction of the bilateral adrenal cortex and often occurs in patients with a preexisting history of autoimmune disease (eg, hypothyroidism, type 1 diabetes mellitus). Acute adrenal insufficiency (adrenal crisis) Etiology Adrenal hemorrhage or infarction Illness/injury/surgery in patient with chronic AI Pituitary apoplexy Clinical features Hypotension & shock Nausea, vomiting, abdominal pain Fever, generalized weakness Treatment Hydrocortisone or dexamethasone Rapid intravenous volume repletion AI = adrenal insufficiency.dddddddd

Embryological cause of: - Cleft Lip - Cleft Palate

- Cleft Lip: Failure of the maxillary prominence and the intermaxillary segment to fuse during weeks 5-6. - Cleft Palate: Failure of the palates to fuse during weeks 7-8.

Celiac Disease: - Main two risks / complications (i.e., these pts are most likely to develop ___ or ___) - HIGH YIELD: What part of the bowel is affected most by celiac disease?

- Main 2 risks: Small Intestines Cancer and T-cell Lymphoma (both unique) - DUODENUM is affected most > In tropical sprue, ileum (B12) and jejunum (Folate) are affected most.

What is secreted by: - Zona glomerulosa - Zona fasciculata - Zona reticularis (MNEMs - one with my initials)

- Zona glomerulosa: Mineralocorticoids (aldosterone) - Zona fasciculata: Glucocorticoids (Cortisol) - Zona reticularis: ​​​​​​​Sex Hormones (Androgens) MNEM: Go Find Rex, Make Good Sex: G - glomerulosa, F - fasciculata, R - reticularis M - mineralcorticoids, G - glucocorticoids, S - sex hormones. Or ACS for GFR Aldosterone Cortisol Sex hormones And the medulla produces Epi / NE

++++ "Shows Up All The Time on STEP1" ++++ From YouTube NBME 20 Walkthrough Episiotomies (cutting the vagina during childbirth): BOTH 1 & 2 are the high yield topics related to this. 3 is also fair game. 1. A woman has had fecal incontinence since giving birth. Which of the following is the most likely cause of the fecal incontinence in this patient? A. Achalasia of the internal anal sphincter B. Damage to the anal sphincter C. Increased pressure of the anal sphincter D. Spastic contraction of the puborectalis muscle E. Spastic external anal sphincter 2. An episiotomy is performed to expedite delivery. A vertical, midline incision is made at the posterior vaginal opening through the vaginal and subvaginal mucosa. Which structure was most likely involved in this incision? (i.e., What specific structure is supposed to be cut during an episiotomy?) 3. What nerve is often involved in this process / area and can be anesthesized during procedures?

1) B. Damage to the anal sphincter AMBOSS explains that fecal incontinence is a common complication of episiotomies when the incision goes too far down to the anal sphincter. - NOT increased pressure (C) or spastic contraction (D & E). That's not caused by childbirth, though it could cause fecal incontinence. You have to choose what would fit with BOTH childbirth and fecal incontinence, which is (surgical) damage to the anal sphincter. 2) Perineal Body (see IMAGE) is cut in an episiotomy. Located between the vagina and the anus. EASY: The perineal body is the perineum (taint). This is cut during an episiotomy. If it goes too far down, it'll knick the anal sphincter, leading to fecal incontinence. 3) The Pudendal Nerve (S2-S4) is in this area. It can be anesthesized for procedures. It can also probably be knicked and injured, but just keep this in mind. Overall Associations: Episiotomies — Fecal Incontinence — Anal Sphincter Damage — Perineal Body — Pudendal Nerve IMAGE: • Perineal body: circled in pink, top blue line pointing at it. It's between the vagina and the anal sphincter. This is cut during an episiotomy. • Anal Sphincter: Bottom blue line is pointing at it. Often accidentally damaged during an episiotomy, causing fecal incontinence. • Episiotomy Cut: Yellow vertical line

Antiphospholipid Antibody Syndrome (APLAS): 1. Associated with what disease? 2. Anti-___ and Anti-___ 3. Causes false positive for what disease? 4. Causes a false elevation of what blood lab? 5. Leads to two main clinical findings -- One hematologic and one reproductive.

1. Associated with SLE (30% have APLAS) 2. Characterized by autoantibodies against proteins bound to membrane phospholipids: • Anti-β2 glycoprotein • Anti-Cardiolipin: • Lupus anticoagulant 3. Causes false positive SYPHILLIS test • e.g., positive on one syphillis test but negative on another. • Due to anti-cardiolipin antibody • On a UWorld Q! 4. Falsely elevated PTT lab, but normal PT. • Due to lupus anticoagulant antibody. • On a UWorld Q! 5. Leads to: • Arterial/Venous thrombosis including DVTs, hepatic vein thrombosis • Recurrent unexplained pregnancy loss (miscarriages) due to placental thrombosis.

1. Why do UMN lesions cause hyperreflexia, increased muscle tone, etc.? 2. Why do LMN lesions cause (a) Fasciculations? (b) Hypotonia?

1. Because of the loss of inhibitory modulation from descending pathways, reflex is exaggerated in upper motor neuron disorders. 2. (a) Damaged alpha (lower) motor neurons can produce spontaneous action potentials. These spikes cause the muscle fibers that are part of that neuron's motor unit to fire, resulting in a visible twitch (called a fasciculation) of the affected muscle. (b) Because alpha (lower) motor neurons are the only way to stimulate extrafusal muscle fibers, the loss of these neurons causes a decrease in muscle tone. Reflexes are weak or absent with lower motor neuron disorders, because the alpha motor neurons that cause muscle contraction are damaged. - Some of the likely causes of lower motor neuron lesions are motor neuron disease, peripheral neuropathy, poliomyelitis, and spinal cord injury with nerve root compression. Lower motor neurons control movement in the arms, legs, chest, face, throat, and tongue. Extra Info about UMN lesions from UWorld: Upper motor neurons (UMNs) originate in the cerebral cortex and are responsible for the initiation of voluntary movement. UMN fibers travel through the brainstem and spinal cord to reach lower motor neurons (eg, cranial nerves, spinal nerves), which then innervate muscle fibers. UMN injury can occur anywhere proximal to the anterior horn; common etiologies include stroke (which likely occurred in this patient with multiple risk factors), multiple sclerosis, or spinal cord transection.

Most common cause of intussusception in: - Children - Adults

Children: Enlarged lymph nodes (usually from a virus, such as Rotavirus) Adults: Tumors

Celiac Disease: 1. Sensitive to ___ 2. What type of autoimmune disease? 3. VITAMIN DEFICIENCIES 4. What alleles? 5. What happens to intestines? 6. What happens to skin? What is it called? 7. Commonly deficient in what immunoglobulin?

1. Gluten 2. Immune comlexes when gluten consumed, so Type III. 3. ADEK deficiencies: - Vit D deficiency can lead to low calcium and high PTH. - Leads to anemia too 4. HLA-DQ2 or HLA-DQ8 alleles 5. Loss of villi due to immune complexes that trigger CD8 T-cell destruction of intestinal tissue. 6. Dermatitis Herpetiformis -- itchy red papulo-vesicular lesions on elbows, shoulders, and knees. 7. Lots are deficient in IgA, leading to repeated infections. Due to anti-IgA.

+++++++++++++++++++++++ Glycogen Storage Diseases (impairments in glycogenolysis) - Name the deficient enzyme for each presentation: 1. Exercise intolerance and weakness, muscle cramps, rhabdomyolysis (dark urine). Symptoms improve if patient drinks glucose before exercising. 2. Hepatomegaly, steatosis, fasting hypoglycemia (low blood sugar if not eating), Lactic acidosis, Hyperuricemia (high uric acid) and Hyperlipidemia (high lipids). 3. Hepatomegaly, ketotic hypoglycemia (high ketone bodies and low serum glucose), poor muscle tone, weakness, abnormal glycogen with ver short outer chains. 4. Normal serum glucose level, large heart (severe cardiomegaly), accumulation of glycogen in lysosomes.

1. Glycogen phosphorylase in the muscle; i.e., Myophosphorylase. Can't break down muscle glycogen. McArdle Disease (Type V GSD). - e.g., A 15-year-old boy is being evaluated for poor exercise endurance. He recently started weightlifting with some of his friends and is disappointed that he is "the weakest one by far." He says he tries as hard as possible, but his "arms feel like jelly after just a few repetitions." The patient also says he sometimes experiences severe muscle cramping and urine discoloration after periods of intense straining. Further evaluation reveals that his exercise tolerance can be greatly improved by drinking an oral glucose solution before beginning a strenuous activity. 2. Von Gierke Disease (Type I GSD). Missing Glucose 6 phosphatase. - Unable to convert glucose-6-phosphate to glucose 3. Debranching enzymes are missing. Cori disease (Type III GSD) - e.g., An infant boy has repeatedly experienced hypoglycemia and seizures. On exam, you note decreased muscle tone, growth retardation, and hepatomegaly. The patient has normal serum lactate. Further biochemical testing reveals abundant glycogen with abnormally short outer chains 4. Acid α-glucosidase is missing. Pompe disease (Type II GSD)

++++++++++ HIGH YIELD ++++++++++ +++++++ Several UWorld Qs +++++++ Diagnosing the CAUSE of Cushing Syndrome (high cortisol and cushing sxs): 1. If ACTH level is low to begin with, high cortisol is due to ___ or ___. 2. If ACTH is normal or elevated despite elevated cortisol, you do a high dose dexmethasone test (potent glucocorticoid). Diagnosis if high dose dexmethosone: a) Suppresses ACTH and Cortisol levels b) Does not affect ACTH and Cortisol levels

1. If ACTH level is low to begin with, high cortisol is due to either an adrenal tumor or exogenous glucocorticoid use (e.g., immunosuppression, inhaled corticosteroids for asthma, etc.) 2. If ACTH is normal or elevated despite elevated cortisol, you do a high dose dexmethasone test (potent glucocorticoid). Diagnosis if high dose dexmethosone: a) Suppresses ACTH and Cortisol levels: Pituitary Adenoma b) Does not affect ACTH and Cortisol levels: Ectopic ACTH secretion (e.g., small cell lung cancer) A Cushing's patient has high cortisol and features such as weight gain, proximal muscle weakness, hypertension, and hyperglycemia. Screening tests for endogenous Cushing syndrome include low-dose dexamethasone suppression testing. In normal individuals, low doses of dexamethasone (a potent glucocorticoid) suppress ACTH and cortisol levels through negative feedback. However, in endogenous Cushing syndrome, ACTH and cortisol levels are not suppressed. The most common causes of Cushing syndrome are shown in the flowchart and can be categorized on the basis of serum ACTH levels as either ACTH dependent (ACTH is high or inappropriately normal) or ACTH independent (ACTH is suppressed). In ACTH-dependent Cushing syndrome, if high-dose dexamethasone suppresses ACTH and cortisol secretion, a pituitary source of ACTH (ie, ACTH-secreting pituitary adenoma) is likely. In contrast, ectopic ACTH production (eg, from malignant tumors such as small cell lung cancer) is not suppressed by high-dose dexamethasone.

++++++++++++ Very High Yield ++++++++++++++++ 3 steps of granuloma formation, including immune mediators: - First ___ presents antigen to CD4+ helper T-cell - Involves IL-__ which turns CD4+ T-cell into which subtype? - Then ___ converts macrophages into epithelioid histiocytes and giant cells MedBullets A 48-year-old immigrant from Vietnam presents with fever, weight loss, a persistent cough, and malaise. His symptoms began three months ago and have worsened over time. A sample of the patient's sputum reveals acid-fast bacilli and chest radiograph is shows a density in the right upper lobe. Which cell type is responsible for the formation of the granuloma? A. Neutrophils B. Th2 lymphocyte C. CD8 T cell D. Th1 lymphocyte E. Natural killer cells

1. Macrophages present antigen to CD4+ T cells using MHC II 2. Macrophages secrete IL-12 to induce CD4+ T cells to become Th1 subtypes 3. Th1 secretes IFN-Gamma, which converts macrophages to epeithelioid histiocytes and giant cells - TNF also involved Simplified: 1. Macrophages find antigens and use MHC Class II to show them to CD4+ helper T-cells. 2. Macrophages dump IL-12 into CD4+ helper T-cells which turns them into the Th1 subtype 3. Th1 cells secrete Interferon gamma, which then converts macrophages to epeithelioid histiocytes and giant cells IL-12 from macrophages - HIGH YIELD - in both caseating and noncaseating granulomas IFN-gamma from Th1 helper T-cells (Th1 always secretes IFN-gamma. IFN-gamma always activates macrophages in some way) MedBullets Question: D. Th1 lymphocyte Th1 lymphocytes are the only option involved in granuloma formation.

Diagnose each thyroid condition: 1. Characterized by branching papillary structures with interspersed concentric calcifications (psammoma bodies). Thyroid palpation shows nodular enlargement that is nontender. 2. Follicular hyperplasia with tall cells forming intrafollicular papillary projections. Iodine uptake is decreased. Thyroid palpation shows nodular enlargement that is nontender. 3. Tall cells with follicular hyperplasia, but radioiodine uptake is increased due to excessive TSH receptor stimulation. 4. From parafollicular "C cells"; produces calcitonin, sheets of polygonal cells in an amyloid stroma (stains with Congo red). Associated with MEN 2A and 2B (RET mutations).

1. Papillary thyroid cancer - IMAGE - Psammoma bodies. - UW: Papillary thyroid cancer is characterized by branching papillary structures with concentric calcifications (psammoma bodies). 2. Tall cell variant of papillary thyroid cancer - UW: The tall-cell variant of papillary thyroid cancer is characterized by follicular hyperplasia lined by tall epithelial cells. 3. Grave's Disease - UW: Graves disease can also cause tall cells with follicular hyperplasia, but radioiodine uptake is increased due to excessive TSH receptor stimulation. 4. Medullary thyroid cancer - FA: From parafollicular "C cells"; produces calcitonin, sheets of polygonal cells in an amyloid stroma (stains with Congo red). Associated with MEN 2A and 2B (RET mutations).

Diagnose each important type of thyroiditis: 1. Onset following a viral illness. Painful / Tender thyroid enlargement. Transient hyperthyroid symptoms. ↑ ESR & CRP. ↓ Radioiodine uptake. Histology: Mixed cellular inflammatory infiltrate with macrophages & giant cells. 2. Painless / Nontender thyroid enlargement. Predominant hypothyroid features. Positive TPO antibody. Variable radioiodine uptake. Histology: Mononuclear, parenchymal, ymphocytic infiltrate with well-developed germinal centers and Hürthle cells (eosinophilic epithelial cells). 3. Characterized by extensive fibrosis of the thyroid gland that extends beyond the thyroid capsule into surrounding tissues. The thyroid gland is hard (as a rock) and nontender.

1. Subacute granulomatous thyroiditis (SGT), also called de Quervain thyroiditis. SGT typically follows an acute viral illness and is thought to be due to a cross-reacting immune response against viral proteins or tissue antigens released during cellular injury. Patients may experience a transient hyperthyroid phase (elevated thyroxine [T4], suppressed TSH) due to release of stored thyroid hormone. Radioiodine uptake is decreased in SGT as the low TSH levels suppress synthesis of new thyroid hormone. Resolves in 6 weeks and patients may have a brief hypothyroid phase before returning to a euthyroid state (thyroid used up). Histology BUZZword: multinucleated giant cells. 2. Chronic lymphocytic (Hashimoto) thyroiditis is characterized by diffuse, painless thyroid enlargement, often with symptoms of hypothyroidism (eg, fatigue, cold intolerance). Biopsy reveals diffuse lymphocytic infiltration with formation of germinal centers. It is autoimmune. 3. Riedel thyroiditis - Hard as a rock.

Meckel Diverticulum: - Definition. True or False diverticulum? - Caused by failure of the ___ to ___. Also by failure of the ___ duct to be obliterated. - Presentation and appearance - Rule of 2's (helps you remember features)

A common congenital condition in which there is an outpouching of all 3 layer (TRUE diverticulum) of the small intestines wall / mucosa. HIGHEST YIELD: Causes: 1. Failure of the VITILLINE DUCT to involute. BUZZword. 2. Failure of obliteration of the paramesonephric duct. IMAGE: From Pathoma. Top part is normal S.I. going from right to left. The meckel diverticulum is the outpouching below that involving ALL 3 layers of the mucosa. Outpouching goes towards the umbilicus. Presents in first 2 years of life with NO VOMITING, but bleeding, volvulus, intussusception, or obstruction. - Passing of meconium (first poop) through the umbilicus. Rule of 2's: - Presents in first 2 years of life - 2% of the population has one - 2 inches long and located w/in 2 feet of the ileocecal valve. A/w development of ulcers. MedBullets: A mother brings her 2-year-old son to the pediatrician due to intermittent abdominal pain, vomiting, and one episode of dark red stools. The child has otherwise been healthy and growing normally. On physical exam, the patient is irritable with guarding of the right lower quadrant of the abdomen. Based on clinical suspicion, pertechnetate scintigraphy demonstrates increased uptake in the right lower abdomen. He undergoes laparoscopic surgery. An outpouching of tissue is excised from the ileum and sent to the laboratory for evaluation. The pathologist notes inflammation and the presence of mucosa, submucosa, and muscle in the walls of the specimen. Which of the following is associated with this patient's condition? - Answer: Abnormal closure of the vitilline duct

+++++ Never Provided but Usually Important +++++ A normal LV ejection fraction is at least ___% A LV ejection fraction below ___% = Heart Failure

A normal heart's ejection fraction is at least 55% -- between 50 and 70 percent is fine. So a little over half is normal. Ejection fraction <50% = Heart Failure - not even ejecting half of the LV blood

+++++++++ IMPORTANT CONCEPT, UWORLD +++++++++ A 44-year-old man comes to the hospital due to acute onset of central chest pain radiating to the left arm. He used cocaine a few hours ago. Blood pressure is 160/100 mm Hg, pulse is 98/min, and respirations are 18/min. On examination, the patient appears anxious and diaphoretic. Electrocardiogram shows ST-segment elevation in the anterior leads. Laboratory studies reveal an elevated cardiac troponin level and a serum potassium concentration of 3.1 mEq/L. Which of the following is the most likely cause of this patient's hypokalemia? A. Increased inctracellular shift of potassium B. Increased urinary loss of potassium

A. Increased inctracellular shift of potassium This patient with a cocaine-induced myocardial infarction most likely developed acute hypokalemia due to stress-related beta-adrenergic hyperactivity, which causes potassium to shift intracellularly. Epinephrine activates the beta-2 receptor, leading to increased activity of the sodium-potassium ATPase pump and the sodium-potassium-2-chloride cotransporter, both of which transport potassium intracellularly. Adrenergic activity also stimulates the release of insulin, which further promotes intracellular potassium shifting. See IMAGE: Most of the time, hypokalemia will be due to intracellular shift. This includes insulin, increased SNS activity, and alkalosis. Similar intracellular shifts can be seen with beta-agonist medications (eg, albuterol, dobutamine) and sympathomimetics (eg, pseudoephedrine). Patients with other sources of potassium loss (eg, diuretics, diarrhea) are at increased risk. NOT Increased urinary potassium loss - that can occur with diuretic use and in the setting of elevated aldosterone levels (eg, renovascular disease, primary aldosteronism). Although hyperaldosteronism is associated with hypertension, this patient's elevated blood pressure is likely from cocaine use, not the MI.

+++++++++++++++++++++ +++++++ UWorld ++++++ A 47-year-old man comes to the office due to worsening shortness of breath for several months. The patient has no fever, weight loss, or cough. He has no other medical conditions and takes no medications. The patient does not use tobacco, alcohol, or illicit drugs. Vital signs are normal. Pulmonary examination demonstrates wheezing and poor air movement. Laboratory results are as follows: Platelets 160,000/mm3 Leukocytes 6,500/mm3 Creatinine 0.8 mg/dL Total bilirubin 1.3 mg/dL Aspartate aminotransferase (SGOT) 112 U/L Alanine aminotransferase (SGPT) 124 U/L A liver biopsy is subsequently performed. Light microscopy of the tissue specimen after treatment with diastase and periodic acid-Schiff staining shows intracellular granules within the periportal hepatocytes. Given these findings, what is the most likely cause of this patient's shortness of breath?

A1AT deficiency - interalveolar septa destruction Look for Liver + Lung problems -- A!AT is in both This patient has alpha-1 antitrypsin (AAT) deficiency, an autosomal codominant disorder that can affect the lungs and liver. Produced primarily in the liver, AAT is a serum protein that inhibits several different proteolytic enzymes (in particular, neutrophil elastase), thereby reducing tissue damage caused by inflammation. Most individuals with AAT deficiency eventually develop severe panacinar emphysema due to unchecked destruction of the interalveolar septa (which contain large amounts of elastin). Smoking plays a synergistic role in the disease process by inducing lung inflammation and permanently inactivating AAT through oxidation of a crucial methionine residue. Therefore, smokers with AAT deficiency tend to develop dyspnea at a median age of 36 versus a median age of 51 in nonsmokers. Some patients with AAT deficiency develop liver disease due to intrahepatocyte accumulation of polymerized AAT molecules; the liver disease can progress to cirrhosis (the second most common cause of death behind emphysema in this population) and hepatocellular carcinoma. - Histologically, intracellular granules of unsecreted AAT are seen within the periportal hepatocytes.

++++++++ Remarkably High Yield!!! ++++++++ What does Cytochrome C do?

Activates APOPTOSIS Lack of Bcl2 allows cytochrome c to leak from inner mitochondrial matrix into cytoplasm to activate caspases, which do the dirty work. - Bcl2 inhibits apoptosis until there's DNA damage or cell injury (i.e., signs of a bad cell), and then Bcl-2 is inactivated to allow apoptosis to occur. Caspases cause apoptosis by (a) activating proteases which degrade the cytoskeleton of the cell membrane and (b) activating endonucleases that break down DNA. NOTE: Don't confuse this with cytochrome c oxidase, which transfers electrons to oxygen in the last step of oxidative phosphorylation.

+++++++ HIGH YIELD, MULTIPLE Q's +++++++ Classic presentation: A patient with PANCREATITIS is likely to develop what respiratory condition?

Acute Respiratory Distress Syndrome - answer to one Q was hyaline membranes are likely to be found on autopsy - answer to another Q was that PCWP would be normal in this pt, but capillary permeability, lung compliance, V/Q matching, and work of breathing would all be abnormal

+++++++++++++++++++++ +++++++ UWorld ++++++ What is the effect of an aspirin overdose​​​​​​​ on respiratory rate, blood pH, PCO2, bicarb, and other respiratory parameters?

Acute salicylate intoxication typically presents with nausea/vomiting, dizziness, confusion, tinnitus (eg, ringing/buzzing sound), fever, and tachypnea within several hours after ingestion. Two different acid-base abnormalities are characteristic: • Respiratory alkalosis - occurs because salicylates directly stimulate the medullary respiratory center, resulting in increased ventilation and loss of CO2 in the expired air. • Anion gap metabolic acidosis - HCO3- and PCO2 change in the same direction -- both DECREASE! This develops because toxic salicylate levels increase lipolysis, uncouple oxidative phosphorylation, and inhibit the citric acid cycle. This results in the accumulation of unmeasured organic acids in the blood (eg, ketoacids, lactate), increasing the anion gap. Therefore, salicylate toxicity classically presents with a mixed acid-base disturbance, with arterial blood gas sometimes showing a pH within the normal range as the 2 primary disturbances shift the pH in opposite directions. There is LOW serum HCO3- due to primary metabolic acidosis and low PaCO2 due to both respiratory compensation for the metabolic acidosis and the primary respiratory alkalosis. Because of the mixed disturbance, the PaCO2 is lower than expected for respiratory compensation alone (ie, per Winters' formula the expected PaCO2 due to respiratory compensation is ~23 mm Hg, but the primary increase in central respiratory drive pushes PaCO2 even lower).

Official list of drugs associated with adverse renal effects

Adverse effects of drugs on the renal and urinary system: ACE inhibitors aminoglycosides amphotericin B cisplatin furosemide gadolinium (nephrogenic systemic fibrosis) iodinated contrast dye lithium NSAIDs penicillins sulfa drugs tenofovir drug -induced urinary retention - usually a cholinergic

+++++++++++++++++++++ Angiotensin II has what effect on which glomerular arteriole? How does this affect net filtration pressure?

Angiotensin II constricts the efferent arteriole, resulting in an increased hydrostatic pressure gradient and an increased net filtration pressure. - Ang II increases GFR, which increases the amount that is filtered and the pressure in the capillaries. The net filtration pressure is a result of pressure gradients formed by Starling forces and is calculated by subtracting the oncotic pressure gradient from the hydrostatic pressure gradient: net filtration pressure = [Pc − Pi] − [πc − πi] MNEM: H-O, C-I -- HO CI or HOCI ("hochi")

A patient with asthma (and taking inhaled corticosteroids) or cystic fibrosis with eosinophilia and bronchiectasis most likely has recurrent pulmonary infections from what pathogen?

Aspergillus! Allergic Bronchopulmonary Aspergillosis (ABPA) Asthmatics are specifically predisposed to Aspergillus pneumonia and BRONCHIECTASIS is a specific finding. Aspergillus fumigatus is a low virulence fungus that generally does not cause significant infections except in immunocompromised or debilitated patients. It may, however, colonize the bronchial mucosa. Patients with asthma or cystic fibrosis in particular may develop an allergic hypersensitivity reaction to the fungus. The result is allergic bronchopulmonary aspergillosis (ABPA), which occurs in 5%-10% of corticosteroid-dependentasthmatics. Patients with ABPA have very high serum IgE levels, eosinophilia, and IgE plus IgG serum antibodies to Aspergillus. There is intense airway inflammation and mucus plugging with exacerbations and remissions. Repeated exacerbations may produce transient pulmonary infiltrates and proximal bronchiectasis. UWorld Q: A 34-year-old woman comes to the office for evaluation of recurrent transient pulmonary infiltrates. The patient has a history of bronchial asthma and has had several exacerbations over the past few years, particularly during the winter months. She is currently asymptomatic. She has no other medical problems and has never traveled outside the United States. Her medications include albuterol as needed and medium-dose inhaled glucocorticoids. Temperature is 37.1 C (98.8 F). Physical examination is unremarkable. Complete blood count shows eosinophilia. A chest CT scan reveals proximal bronchiectasis. This patient's condition is most likely related to colonization with which of the following? - Answer: Aspergillus

​​​​​​​+++++++++++++++++++++++++++ Name the gene mutation associated with each set of cancers: 1. Colon, Endometrial, Ovarian 2. Colon, Osteomas (bone), Brain tumors 3. Hemangioblastomas (brain), Clear cell renal carcinoma, Pheochromocytoma 4. Sarcomas, Breast cancer, Brain tumors, Adrenal tumors, Leukemia 5. Parathyroid, Pituitary, and Pancreatic adenomas 6. Medullary thyroid cancer, pheochromocytoma, parathyroid hyperplasia

Autosomal Dominant, Inactivation of a tumor supressor gene: 1. MSH2, MLH1, MSH6, PMS2 (Lynch Syndrome) - Colon, Endometrial, Ovarian 2. APC (Familial Adenomatous Polyposis) - Colon, Osteomas (bone), Brain tumors 3. VHL (von Hippel-Lindau syndrome) - Hemangioblastomas (brain), Clear cell renal carcinoma, Pheochromocytoma 4. TP53 (Li-Fraumeni Syndrome) - Sarcomas (bone), Breast cancer, Brain tumors, Adrenal tumors, Leukemia 5. MEN1 (Multiple Endocrine Neoplasia 1) - Parathyroid, Pituitary, and Pancreatic adenomas Autosomal Dominant, Activation of an oncogene: 6. RET (Multiple Endocrine Neoplasia 2) - Medullary thyroid cancer, pheochromocytoma, parathyroid hyperplasia

++++++++++++++++++ In general, most enzyme deficiencies have what inheritance pattern?

Autosomal Recessive e.g., Galactosemia

+++++++++++++++++++++++++++ Leukemia: Tdt+ indicates ... CD 10 and CD 19 = ___ CD 1, CD 2, and CD 5 = ___ Peroxidase positive indicates ___

B-ALL and T-ALL are Tdt+ - So Tdt+ just tells you it's a lymphoblastic leukemia. Could be B-ALL or T-ALL. B-ALL has CD's above 8 (CD10, CD19) - Typically in younger children T-ALL has CD's below 8 (CD1, CD2, CD5) - Typically in Teenagers with a Thymic / mediastinal mass. Peroxidase + = AML/APML - Peroxidase = Auer rods

+++++++ NBME 20 Question - YouTube +++++++ A study is conducted to assess the effect of a new screening test on the mortality rate of prostate cancer. Prior to implementation of screening, the overall 5-year survival rate was 70%. After initiating the screening in the randomly selected study population, the 5-year survival rate increases to 85%. During this time, there were no changes in the treatment of prostate cancer. The apparent decrease in mortality could be due to which of the following types of bias? A. Compliance B. Lead-time C. Recall D. Selection

B. Lead-time Lead-time bias is caused by earlier detection being confused with an increased survival. Here, survival was not impacted at all since it was a SCREENING test. Patients should have been compared by their disease severity. Lead time bias refers to the phenomenon where early diagnosis of a disease falsely makes it look like people are surviving longer. This occurs most frequently in the context of screening. Just because I got diagnosed 10 years ago by screening and another person got diagnosed yesterday but we both died on the same day doesn't mean that I survived 10 years longer or that the screening helped me survive.

++++++++++++ UWorld +++++++++++++ A former alcoholic suddenly develops shortness of breath and dies. Autopsy examination is performed, and histopathology of the lungs reveals engorged pulmonary capillaries and intraalveolar, acellular, pink material that is more prominent at the bases. This patient most likely had which of the following conditions? A. Centriacinar emphysema B. Pulmonary Edema C. Pulmonary arterial hypertension D. Pulmonary infarction E. Aspiration pneumonia And for the other options, what would histology and presentation reveal?

B. Pulmonary Edema Engorged alveolar capillaries reflect increased pulmonary venous pressure. Pink, acellular material within the alveoli results from transudation of fluid plasma (BLOOD) across the alveolar-capillary membrane. These histopathologic findings are most consistent with acute pulmonary edema caused by increased alveolar capillary hydrostatic pressure from left-sided heart failure. This patient likely had dilated cardiomyopathy due to chronic alcohol abuse and had an acute exacerbation of heart failure, resulting in cardiogenic shock with pulmonary edema and acute respiratory failure. Dilated CM => Heart Failure => Pulmonary Edema - that's how dilated CM can cause pulmonary edema Summary: Acute cardiogenic pulmonary edema results from increased pulmonary venous pressure. The alveolar capillaries become engorged with blood and there is a transudation of fluid plasma across the alveolar-capillary membrane, appearing as pink, acellular material within the alveoli. Wrong answers: - Aspiration pneumonia may be chemical (eg, aspiration of gastric contents) or bacterial (eg, aspiration of oral flora). Histopathology shows neutrophil-rich, inflammatory exudates within the bronchioles and alveolar spaces. - Centriacinar emphysema most commonly results from heavy smoking. Enlarged airspaces with macrophage-predominant infiltrates are expected. ​​​​​​​- Histopathology in pulmonary arterial hypertension shows hypertrophy of the pulmonary vascular smooth muscle. - Pulmonary infarction yields hemorrhagic, ischemic necrosis of the lung parenchyma. Histopathology shows a well-demarcated area of alveolar and vascular wall necrosis with cells that lack nuclei, and the alveolar spaces may contain red blood cells.

Chromogranin A positive is a BUZZword for a ___ tumor

Carcinoid tumor

+++++++++ UWorld ++++++++++ Common Q / Answer Choice A 35-year-old man comes to the clinic for evaluation of exertional dyspnea and dry cough for 8 months. Oxygen saturation on room air while lying down is 96% and drops to 88% after 6 minutes of walking. Examination shows fine crackles in both lower lungs. Chest x-ray reveals reticular densities in both lung fields. Lung biopsy shows an infiltration of inflammatory cells, predominantly lymphocytes, as well as poorly formed noncaseating granulomas and moderate alveolar septal fibrosis. Which of the following is the most likely diagnosis? A. Bronchial asthma B. Chronic bronchitis C. Hypersensitivity pneumonitis D. Idiopathic pulmonary fibrosis E. Pulmonary tuberculosis

C. Hypersensitivity pneumonitis See IMAGE for all details. Summary: Hypersensitivity pneumonitis involves an exaggerated immunologic response to an inhaled antigen and can have an acute or chronic presentation. Chronic disease presents with gradually progressive cough, dyspnea, fatigue, and weight loss, and lung biopsy reveals lymphocytic infiltrate, poorly formed noncaseating granulomas, and septal fibrosis. Details: This patient with chronic dyspnea and cough accompanied by characteristic lung biopsy findings most likely has hypersensitivity pneumonitis (HP). HP is an exaggerated immunologic response to an inhaled antigen; common offending agents include mold, bacteria, animal protein, and chemicals. The condition has variable presentation that is largely dependent on the dose and chronicity of antigen exposure: 1. Acute HP involves abrupt-onset and often recurring episodes of fever, chills, cough, dyspnea, and fatigue that coincide with intermittent high-dose antigen exposure. Leukocytosis is often present. Chest x-ray may be normal or show scattered micronodular opacification. 2. Chronic HP involves persistent and gradually progressive symptoms (as in this patient) resulting from long-term, moderate-dose antigen exposure. Patients usually have symptoms of cough, dyspnea, fatigue, and weight loss for several months or more. Lung auscultation usually reveals fine crackles, and chest x-ray shows interstitial reticular opacities consistent with the development of pulmonary fibrosis.

+++++++++++++++++++++++++ UWorld A 52-year-old woman comes to the emergency department due to increasing dyspnea and chest tightness over the past 2 weeks. She has a history of stage 4 chronic kidney disease due to chronic glomerulonephritis. Temperature is 36.6 C (97.8 F), blood pressure is 106/82 mm Hg, and pulse is 98/min. Systolic blood pressure decreases by 12 mm Hg during inspiration. Physical examination shows distant heart sounds and clear lungs. Diagnose

Cardiac Tamponade

What does CAN stand for in the Whipple Disease mnemonic PAS the foamy whipped cream CAN?

Cardiac sxs Arthralgias Neuro sxs Affects the lamina propria of the S.I. -- that's where the foamy macrophages are.

++++++++ UWorld +++++++++ Diagnose: A 43-year-old woman says she cannot sleep due to pain and tingling affecting the first three digits of both hands. She has no problems with her legs. The patient suffers from chronic renal failure due to uncontrolled hypertension and receives hemodialysis. On examination, she has bilaterally diminished sensation over the thumb, index and middle fingers, and the radial half of her ring finger.

Carpal Tunnel Syndrome - UW answer: nerve compression within an anatomic compartment - it was in her hands only - hence, compartment Carpal tunnel syndrome (CTS) is a peripheral mononeuropathy caused by compression of the median nerve in the carpal tunnel. The carpal tunnel is an area located on the palmar surface of the wrist (between the carpal bones and transverse carpal ligament) in which the median nerve and tendons of the long flexors of the digits pass through. There is little room for expansion in this anatomical compartment. CTS is associated with conditions that reduce carpal tunnel space, including pregnancy (fluid accumulation), hypothyroidism (glycosaminoglycan buildup), diabetes mellitus (connective tissue thickening), and rheumatoid arthritis (tendon inflammation). Patients with a long history of hemodialysis can also develop median nerve compression through deposition of β2-microglobulin (dialysis-associated amyloidosis) in the carpal tunnel. Symptoms and signs of CTS often occur bilaterally and include: 1) Sensory impairment, pain, and/or paresthesias in the median nerve distribution (palmar surface of the first 3 digits and radial half of the 4th digit). Symptoms are usually worse at night. 2) Motor weakness during thumb abduction/opposition and thenar atrophy. 3) Tinel sign (tapping over the flexor surface of the wrist reproduces symptoms) and Phalen sign (flexion of the wrist reproduces symptoms).

++++++++ UWorld +++++++++ CENTRIACINAR emphysema: - usually results from ___ - what will you see on lung biopsy? PANACINAR emphysema results from what?

Centriacinar emphysema most commonly results from heavy smoking. Histology will show enlarged airspaces with macrophage-predominant infiltrates -- IMAGE Panacinar emphysema results from A1AT deficiency.

Polymyositis: - Clinical presentation (muscle weakness pattern) - What muscle enzymes are usually elevated? - What are the 2 main antibodies associated with this condition? - Muscle biopsy shows infiltration of what type of cells? - 2 conditions associated with this (comorbidities)

Clinical presentation: - Symmetrical proximal muscle weakness - Increasing difficulty climbing stairs, getting up from a chair, carrying heavy objects. Starts with weakness in shoulders / hips / etc. and progresses to difficulty standing and combing hair. Pathologic features: 1. Elevated muscle enzymes (Creatine Kinase, aldolase) 2. Autoantibodies: ANA (antinuclear antibodies), anti-Jo-1 3. Muscle Biopsy: Endomysial mononuclear infiltrate, patchy necrosis. "MHC class I molecule overexpression on the sarcolemma with CD8+ lymphocyte infiltration" -- hence polymyositis -- inflammation w/ infiltration of CD8+ T-cells. Associated complications: Lungs and Heart - Interstitial lung disease - Myocarditis

+++++++++ HIGH YIELD, Multiple UWorld Qs +++++++++ Cramping in lower extremity muscles in a kid or young adult plus different blood pressures in the brachial and femoral arteries (diminished or delayed pulses in the femoral arteries) is in every stem for what heart disformity? What congenital condition is HIGHLY associated with this congenital heart condition?

Coarctation of the aorta in a child/young adult presents with lower-extremity claudication (eg, pain and cramping with exercise), blood pressure discrepancy between the upper and lower extremities, and delayed or diminished femoral pulses. - Just remember: Aorta has a narrowing in this condition, so it's harder to get enough blood to reach inferior limbs. HIGHLY and CLASSICALLY associated with Turner syndrome (45,XO) (girl) is associated with coarctation of the aorta in 1/10 cases. Sample UWorld stem (QID 30): A 12-year-old girl is brought to the physician by her parents, who are concerned about her loss of interest in playing sports at school. During a recent competition, she walked off the field in the middle of the game, complaining about the pain in her legs. The patient has no other medical conditions and takes no medications. Her vaccination schedule is up-to-date. Physical examination shows pulsatile vessels within the intercostal spaces and diminished femoral pulses relative to brachial pulses. This patient's symptoms are most likely associated with which of the following conditions?

++++++++ UWorld Q ++++++++++ A patient has mental deterioration after a subarachnoid hemorrhage and a CT finds enlargement of ventricles. By what mechanism can a subarachnoid hemorrhage cause hydrocephalus?

Communicating hydrocephalus is a common complication of subarachnoid hemorrhage that presents with deteriorating mental status. It typically results from blood-induced impairment of absorption of cerebrospinal fluid by the arachnoid granulations. A lot of CSF is absorbed in the subarachnoid space, so if there's blood there, CSF will build up and cause hydrocephalus.

Tracheoesophageal fistula (TEF) • Presentation • CXR shows ... • ___draminos in the mother

Congenital defect resulting in a connection between the esophagus and trachea • Neonate who vomits undigested food, drools, and chokes • CXR shows air bubbles in the stomach because TEF lets air into esophagus from trachea. • Polyhydraminos in the mother because fetus can't swallow as much amniotic fluid.

++++++++++++++++ ​​​​​​​A 22-year-old woman comes to the office due to palpitations, weight loss, and insomnia. She has lost 7 kg (15.4 lb) in the past 3 months. The patient has no other medical problems and takes no medication. She does not use tobacco, alcohol, or illicit drugs. Blood pressure is 130/80 mm Hg and pulse is 104/min and regular. The thyroid gland is diffusely enlarged and nontender on palpation. Laboratory studies show markedly decreased serum TSH and elevated thyroxine levels. Methimazole monotherapy is initiated. Two months later, her symptoms had resolved. Methimazole and Propothiouracil decrease thyroid hormone production by directly inhibiting what process by what enzyme?

Coupling of iodotyrosinases Thyroid peroxidase Thioamides (eg, methimazole, propylthiouracil) decrease the formation of thyroid hormones via inhibition of thyroid peroxidase, the enzyme responsible for both iodine organification and coupling of iodotyrosines. Propylthiouracil also decreases the peripheral conversion of T4 to T3. IMAGE: Thyroid follicular cells take up inorganic iodide (iodide trapping) against a concentration gradient using a sodium-iodide symporter. Iodide is then released into the thyroid follicular lumen, where it is oxidized to iodine radical by thyroid peroxidase. Iodine then binds to tyrosine residues (organification) in thyroglobulin to form monoiodotyrosine (MIT) and diiodotyrosine (DIT). Coupling of MIT and DIT produces triiodothyronine (T3; MIT coupled with DIT) and thyroxine (T4; two DITs coupled). The thyroid follicular cells then engulf thyroglobulin, which contains the iodinated tyrosine compounds, via pinocytosis. In the thyroid cytoplasm, T3 and T4 (collectively, thyroid hormones) are removed from the rest of the thyroglobulin and secreted from the basolateral border.

+++++++++++++ ALWAYS ON EXAM ++++++++++++++++ A 29-year-old farmer is brought into the emergency department by his friends because he passed out while working in the field and was not able to be aroused. His friends state they thought he had a stomach bug as he was sweating profusely and had diarrhea and vomiting prior to losing consciousness. On exam, the patient's vitals are: T: 36 deg C, HR: 60 bpm, BP: 100/60 mmHg, RR: 12, SaO2: 99%. Diaphoresis, lacrimation, and increased salivation are appreciated. The patient's pupils are constricted. Which of the following medication(s) should be administered to this patient? A. Pyridostigmine only B. Atropine only C. Pyridostigmine and Physostigmine D. Atropine and Pralidoxime E. Sodium Bicarbonate and Pralidoxime

D. Atropine and Pralidoxime - These are anticholinergics that reverse cholinergic poisoning. Use both Atropine (for muscarinic receptors) and Pralidoxime (for nicotinic receptors) This patient is a FARMER -- CLASSIC BUZZwords are farmers that present with DUMBBELLS sxs. Likely exposed to organophosphates in insecticide.

+++++++ NBME 20 Question - YouTube +++++++ A 31-year-old man has a large, yellow, soft mass deeply infiltrating the gluteus maximus muscle. Microscopic examination of the excised mass shows irregular vacuolated cells and clear cells with frequent mitoses. Which of the following is the most likely diagnosis? A. Fibroma B. Fibrosarcoma C. Lipoma D. Liposarcoma E. Rhabdomyoma F. Rhabdomyosarcoma

D. Liposarcoma Lipomas and Liposarcomas are the most common fat tumors. Lipomas are benign while Liposarcomas are malignant. From the histological description (e.g., frequent mitotic figures), this seems malignant. From the gross description (yellow and soft), it sounds like fat. So go with the only malignant fat tumor listed -- Liposarcoma.

EPO is secreted by which part of the kidney? A. Efferent arteriolar smooth muscle B. Glomerular podocytes C. Juxtaglomerular cells D. Peritubular interstitial cells E. Proximal tubule epithelium

D. Peritubular interstitial cells​​​​​​​ NOT Juxtaglomerular cells: These sense solute delivery in the DCT and, if there's decreased renal perfusion or decreased GFR, there will be less solute in the tubules, and the JGA will secrete RENIN

++++++++ UWorld +++++++++ A 43-year-old woman comes to the office due to episodic confusion, blurred vision, tremors, and sweating. The episodes have increased in intensity in the past few months and seem to occur any time during the day. Her symptoms are relieved by drinking orange juice. During a recent episode, the patient's blood glucose level was 32 mg/dL as measured by her husband's home glucose meter. Medical history includes major depression and irritable bowel syndrome. Laboratory studies performed during the next episode of symptoms show the following results: Glucose: 35 mg/dL Insulin: 18 µU/mL (normal: <3 µU/mL) C-peptide: 4.01 ng/mL (normal: <0.6ng/mL) Which of the following is the most likely cause of this patient's symptoms? A. Alpha cell tumor B. Insulin administration C. Somatostatinoma D. Sulfonurea use E. VIP-secreting tumor Essentially know the relationship between insulin and C-peptide.

D. Sulfonurea use Essentially: In this pt, both c-peptide and insulin are low, which makes sense. Those two naturally have a direct correlation. Since her insulin and c-peptide are so high, it's either an insulinoma or she's taking a drug that increases production of real insulin (sulfonurea). If the pt was injecting insulin, C-peptide would be LOW because exogenous insulin has no c-peptide. People with factitious disorder can inject insulin or take oral diabetes medications, such as sulfonureas, which promote the natural production of insulin. (Choice B) Hypoglycemia due to exogenous insulin injection, which does not contain C-peptide, is associated with an elevated serum insulin level but an undetectable C-peptide level. Insulin is initially synthesized as preproinsulin, after which the signal peptide is removed, yielding proinsulin. In the secretory granules, proinsulin is cleaved into insulin and C-peptide, which are then released together in equimolar amounts. Normally, as blood glucose falls, endogenous insulin secretion is suppressed, and serum levels of both insulin and C-peptide drop. Hypoglycemia due to excessive endogenous insulin production (NOT injection) is associated with elevated levels of C-peptide. This can occur due to autonomous insulin-producing tumors (insulinomas) or intake of insulin secretagogues (eg, sulfonylureas). Self-induced hypoglycemia via oral hypoglycemics is often a manifestation of a factitious disorder and is typically seen in health care workers and family members of patients with diabetes using these medications (which is likely in this patient whose husband has home glucose-testing supplies). Sulfonylurea abuse can be confirmed by testing the urine or blood for specific hypoglycemic agents. Other wrong answers: A: Glucagonoma is a rare tumor of pancreatic alpha cells that secretes excessive amounts of glucagon. This results in hyperglycemia, weight loss, anemia, and necrolytic migratory erythema (a raised, erythematous rash affecting the face, groin, and extremities). C: Somatostatinoma is a rare tumor of pancreatic delta cells that is associated with hyperglycemia, weight loss, abdominal pain, steatorrhea, cholelithiasis, and hypochlorhydria. These manifestations are due to somatostatin-induced inhibition of insulin, gastrin, secretin, and cholecystokinin secretion, as well as decreased gastrointestinal motility. E: VIPomas secrete VIP and cause watery diarrhea, hypokalemia, and impaired gastric acid secretion.

+++++++++++++ HIGH YEILD ASSOCIATIONS +++++++++ Name the congenital condition that CLASSICALLY involves each of these cardiac abnormalities: 1. Ostium primum, atrial septal defects, regurgitant atrioventricular valves (Mitral Regurg and Tricuspid Regurg) 2. Tetralogy of Fallot and Interrupted aortic arch 3. Hypertrophic cardiomyopathy (S4 gallop) 4. Cystic medial necrosis (eg, aortic dissection & aneurysm) and Mitral valve prolapse 5. Valvular obstruction due to cardiac rhabdomyomas (i.e., tumor in cardiac muscle) Congenital conditions often affect the heart. These are UWorld's highest yield examples

Down syndrome • Endocardial cushion defects - ostium primum, atrial septal defects, regurgitant atrioventricular valves (Mitral Regurg and Tricuspid Regurg) DiGeorge syndrome • Tetralogy of Fallot • Interrupted aortic arch Friedreich ataxia • Hypertrophic cardiomyopathy Marfan syndrome • Cystic medial necrosis (eg, aortic dissection & aneurysm) • Mitral valve prolapse Tuberous sclerosis • Valvular obstruction due to cardiac rhabdomyomas (i.e., tumor in cardiac muscle)

2 Types of Peptic Ulcer Disease: Gastric Ulcers and Duodenal Ulcers: 1. Food/meals causes increased pain with which kind and decreased pain with which kind? Thus, weight gain vs. weight loss. 2. Most duodenal ulcers are due to ___, but if it says that there is a high level of gastrin, what is the cause? 3. Main 3 causes of gastric ulcers 4. Main risks a/w with each type

Duodenal Ulcers: • Pain Decreases with meals => Weight Gain (food causes neutralizing pancreatic enzymes to be released into the duodenum) • 95% of cases are due to H. pylori (decreased defense against acid). If it says there's a high gastrin level, there's a TUMOR that secretes gastrin and thus increases acid production -- called Zollinger-Ellison Syndrome -- HIGH YIELD / Multiple UWorld Q's! • UNLIKELY to be cancer • Risks are rupture with bleeding and acute pancreatitis. Gastric Ulcers: • Pain is Greater with meals => Weight Loss (makes sense: food in stomach irritates ulcer due to acid release). • Caused by H. pylori, NSAIDs, or Bile Reflux. • Can be cancer or turn into cancer. • Risk of bleeding from Left Gastric a.

+++++++++++ HIGH YIELD, KNOW THIS +++++++++++ ++++++++++++++++++ UWorld Q +++++++++++++++++ (Atherosclerotic Plaque Formation Process) A 68-year-old man has a heart attack. Cardiac enzymes are elevated. Emergent coronary angiography is performed, which demonstrates significant atherosclerotic involvement of the left anterior descending and circumflex arteries. Development of these vascular lesions most likely involved growth factors released from which of the following sources? A. B lymphocytes B. Mastcells C. Erythrocytes D. Neutrophils E. Platelets

E. Platelets - referring to platelet-derived growth factor (PDGF), which is released from platelets, activated macrophages, and endothelial cells NOT neutrophils -- they don't release growth factors. The development of atherosclerotic plaque, or atheroma, involves a multistep process: 1. Initially, factors including hyperlipidemia, hypertension, hyperglycemia, and smoking trigger endothelial injury and/or dysfunction. This leads to increased vascular permeability, enhanced leukocyte adhesion, and a higher propensity for thrombosis. 2. Lipoproteins (ie, LDL and oxidized LDL) enter the arterial wall intima and begin to accumulate. 3. Monocytes adhere to the endothelial wall and enter into the intima as well; turn into macrophages and engulf lipid particles to become foam cells. 4. Platelets adhere to the abnormal endothelium and become activated. 5. Growth factors, namely platelet-derived growth factor (PDGF), are released from platelets, macrophages, and endothelial cells. 6. This triggers smooth muscle cell recruitment from the media and proliferation in the intima. 7. Over time, progressive SMC proliferation and accumulation of necrotic debris (due to macrophage/foam cell and SMC death) lead to growth of the atheroma. SMCs encourage plaque stability by synthesizing collagen, whereas activated inflammatory cells break down collagen and contribute to plaque instability. HDL helps it heal by extracting lipids from the intima back into the bloodstream and to slow atheroma development.

+++++++ NBME Ethics Question +++++++ A 17-year-old girl comes to the emergency department because of a swollen tender ankle. An x-ray of the ankle is strongly suggestive of osteosarcoma. Which of the following next steps is most appropriate? A. Request that an oncologist discuss the findings with them immediately B. Request the presence of the hospital chaplain, then discuss the findings C. Speak with the parents alone about the findings D. Speak with the patient alone about the findings E. Speak with the patient and her parents about the findings

E. Speak with the patient and her parents about the findings "Physicians should always encourage healthy minor-guardian communication." "Also, you're going to do some serious things to treat this girl, possibly amputation, so a minor and her guardians need to be aware." "A really important thing to remember is that people are extremely sensitive and this is a serious matter. Once you start separating people, they know you're hiding something from somebody, which can create a lot of anxiety" - You don't want the patient or the parents to think "Ohhh my gosh, what are they talking about?! What's going on?!" -- unless it's protected information. Just imagine a 10 year old (effectively the same rules here) getting this diagnosis and a doctor talking to the 10 y/o alone. That'd be weird. This is not a private health matter that can be kept from guardians.

++++++++ UWorld +++++++++ A 64-year-old man comes to the emergency department due to chest discomfort and shortness of breath. Medical history includes hypertension, type 2 diabetes mellitus, and severe osteoarthritis of the left knee. The patient is an active smoker with a 20-pack-year smoking history. He undergoes dobutamine infusion with simultaneous cardiac imaging. The following is seen: Before infusion: normal left ventricular contractility, ejection fraction 60% During infusion: decreased contractility, ejection fraction 45% Five minutes after infusion: normal left ventricular contractility, ejection fraction 60% Which of the following best explains the observed findings? A. Coronary artery occlusion due to plaque thrombosis B. Coronary artery vasospasm C. Focal myocardial fibrosis D. Normal myocardial contractile response E. Supply-demand mismatch due to fixed coronary stenosis

E. Supply-demand mismatch due to fixed coronary stenosis Nutshell: Stable angina results from fixed coronary artery stenosis that limits blood flow to downstream myocardium, preventing the myocardial oxygen supply from increasing during exertion. Dobutamine mimics the effects of exercise (SNS agonist) and increases myocardial oxygen demand; it can be used during stress testing to provoke areas of ischemic myocardium, which can be recognized on imaging by a localized and transient decrease in contractility (ie, wall motion defect). This patient with a transient wall motion defect localized to the LV most likely has a fixed atherosclerotic lesion that limits blood flow to that area of myocardium. Stable angina results from fixed coronary artery stenosis in the setting of atherosclerotic coronary artery disease (CAD). Such a stenosis limits blood supply to the downstream myocardium, which, during periods of increased myocardial oxygen demand (eg, exercise or SNS stimulation by Dobutamine), can cause a mismatch of oxygen supply and demand that manifests as anginal symptoms (eg, chest pain, shortness of breath). Pharmacologic stress testing can be useful in diagnosing atherosclerotic CAD. Dobutamine, a beta-1 agonist (SNS stimulator), increases heart rate and contractility to mimic the increase in myocardial oxygen demand that occurs with exercise. Myocardium that is unable to obtain sufficient blood flow to meet this increased oxygen demand typically demonstrates a transient decrease in contractility (ie, wall motion defect), often leading to reduced ejection fraction. This patient with a transient wall motion defect localized to the cardiac apex most likely has a fixed atherosclerotic lesion that limits blood flow to that area of myocardium.

+++++++++++++++++++++++++++++ The main effect of alcohol use is high levels of ___, which causes multiple problems such as hypoglycemia, ketogenesis, and fatty liver

Excess NADH (and low NAD+) Both alcohol breakdown reactions involve NAD+ → NADH, reducing available NAD+. ALWAYS look for an answer involving high NADH. Multiple questions asked about it. LACTATE will be high because high NADH shunts pyruvate to Lactate. This will lead to high anion gap metabolic acidosis.

+++++++++ HIGH YIELD EQUATIONS +++++++++ Equation to calculate GFR from Creatinine Clearance What is the equation for Clearance (particularly of Cr)? How to calculate Renal Plasma Flow (RPF) from PAH clearance +++++++++ UWORLD +++++++++ A longitudinal study is conducted to assess changes in renal function over time in patients with recently diagnosed type 2 diabetes mellitus. An initial set of laboratory tests is obtained in newly enrolled patients to establish baseline renal function parameters. The following measurements are taken from a 42-year-old male volunteer. Creatinine: Urine: 110.0 mg/dL Serum: 1.1 mg/dL Para-aminohippuric acid: Urine: 100 mg/mL Serum: 0.2 mg/mL What is the best estimate of the filtration fraction in this patient assuming a urine flow of 0.1 dL/min?

FF = GFR/RPF C = UV/P GFR = clearance of Creatinine RPF = clearance of PAH So: GFR = Ccr = UV/P RPF = Cpah = UV/P U = Urine Cr V = Urine flow rate (mL/min) P = Plasma Cr Here, creatinine and PAH clearances can be calculated as: Ccr = (110 mg/dl x 0.1 dL/min) / 1.1 mg/dL = 10 dL/min Cpah = (100 mg/ml x 0.1 dL/min) / 0.2 mg/dL = 50 dL/min From these values, FF can then be calculated as: (10 dL/min) / (50 dL/min) = 0.2 or 20%, which is the typical filtration fraction for a healthy individual.

+++++ HIGH YIELD, MULTIPLE UW Q's +++++ Equation for Filtration Fraction If given Renal Blood Flow (RBF) and Hematocrit (as a %), as well as GFR, how do you get to Filtration Fraction? +++++++ UWORLD +++++++ Physiologists are investigating renal autoregulatory mechanisms in an animal species that closely mimics human physiology. During one of their experiments, renal blood flow and glomerular filtration rate are measured in an anesthetized animal in response to changes in mean arterial pressure. Assuming a hematocrit of 0.50, a RBF (Flow Rate) of 1 L/min, what is the best estimate of the filtration fraction?

FF = GFR/RPF If given RBF, RPF = RBF x (1 - Hct) Summary The filtration fraction is the fraction of plasma flowing through the glomeruli that is filtered across the glomerular capillaries into Bowman's space (FF = GFR/RPF). Renal plasma flow can be determined from renal blood flow by multiplying the renal blood flow by (1 - Hematocrit). The filtration fraction (FF) is the fraction of plasma flowing through the glomeruli that is filtered across the glomerular capillaries into Bowman's space. It can be thought of as the ratio between the glomerular filtration rate (GFR) and renal plasma flow (RPF): FF = GFR/RPF RPF is used to calculate FF rather than renal blood flow (RBF) because RBF includes the volume of the blood that is occupied by erythrocytes, a volume unavailable for filtration across the glomerular capillaries. The RPF quantifies the volume of plasma that is able to pass through the glomerular capillaries more accurately and can be calculated from the RBF using the following equation: RPF = RBF x (1 - Hematocrit) Thus, RPF = (1.0 L/min) x (1 - 0.5) = 0.5 L/min Therefore, FF = (0.1 L/min) / (0.5 L/min) = 0.2.

Duodenal Atresia - Definition / Etiology - CLASSIC CXR finding - Highly associated with what congenital condition? (HIGH YIELD) - ___draminos in the mother - Presents with bilious or nonbilious vomiting? Why?

Failure of canalization of the duodenum resulting in polyhydramnios, bile-containing vomitus, and a distended stomach CXR: DOUBLE BUBBLE -- there's a closed portion of the duodenum, so there's a bubble before that (stomach) and after that (duodenum). There's distension of the stomach and a blind loop of the duodenum (duodenum closed off early). Highly a/w DOWN SYNDROME -- HIGH YIELD Polyhydraminos in the mother due to decreased amniotic fluid consumptions. Since the problem is in the duodenum, bile will be in the food, so there will be BILIOUS vomiting

+++++ "Frequently Tested" +++++ A common consequence of Preeclampsia is ___ necrosis of the placenta Pathoma Chapter 1 (Cells)

Fibrinoid necrosis Fibrinoid necrosis is necrosis of a blood vessel wall. Caused by leakage of proteins (including fibrin) into the vessel wall. IMAGE: Fibrinoid necrosis features a hot pink border around the affected blood vessel.

+++++++ High Yield, Keep Getting Wrong +++++++ Name the type of incontinence caused by: 1. Either (a) ↓ urethral sphincter tone, or (b) urethral hypermobility 2. Detrusor muscle hyperactivity 3. Either (a) impaired detrusor contractility, or (b) bladder outlet obstruction Name the type of incontinence that has each of the following symptom descriptions: 1. Leakage with coughing, lifting, sneezing 2. Sudden, overwhelming need to urinate; difficulty holding urine and passing small amounts of urine on the way to the bathroom. A/w early multiple sclerosis. 3. Incomplete bladder emptying (increased post void residual volume) and persistent dribbling. A/w late multiple sclerosis.

For both: 1. Stress incontinence - all about the urethra 2. Urge incontinence - OVERactive detrusor muscle; SNS / PNS innervation problems. 3. Overflow incontinence - UNDERactivity of the detrusor muscle; obstruction of bladder outlet See IMAGE for details Urge incontinence: - Due to detrusor overactivity causing a sudden and/or frequent urge to urinate and empty the bladder. - The micturition reflex is an autonomic spinal reflex mediated by both sensory and motor fibers from nerve centers at the S2-S4 levels. - Parasympathetic stimulation causes detrusor muscle contraction and internal urethral sphincter relaxation. Sympathetic fibers cause internal sphincter contraction and also help with sensing a full bladder. Patients with multiple sclerosis most commonly develop urge incontinence due to loss of central nervous system inhibition of detrusor contraction in the bladder. But as the disease progresses, the bladder can become atonic and dilated, leading to overflow incontinence.

++++++++++++++++++++++++++++++++ High Yield, Always Miss It ​​​​​​​A 15-year-old boy is brought to the office by his mother due to difficulty with movement. The patient enjoys playing high school basketball but had to leave the team this year due to his progressively worsening symptoms. On examination, he is found to have significant kyphoscoliosis and a high plantar arch. His older brother suffered from a neurologic disorder and died of heart failure at age 25. 1. Diagnose 2. Which spinal tracts are degenerated in this disease? 3. What heart condition often develops in this disease? 4. What metabolic condition often develops in this disease? 5. What is the trinucleotide repeat associated with this disease?

Friedreich ataxia is an autosomal recessive disorder caused by mutation of the frataxin (FXN) gene. This gene codes for an essential mitochondrial protein involved in the assembly of iron-sulfur enzymes. An increased number of trinucleotide repeats (GAA) is present in the mutated gene, causing decreased FXN expression. This leads to decreased mitochondrial energy production and increased oxidative stress, resulting in degeneration of neural tracts and peripheral nerves. The following sites of involvement are characteristic: 1. Spinocerebellar and lateral corticospinal tract degeneration causes gait ataxia and spastic muscle weakness, respectively. 2. Degeneration of the dorsal columns and dorsal root ganglia causes loss of position and vibration sensation. 3. Kyphoscoliosis and foot abnormalities (pes cavus = high plantar arch) are characteristic skeletal deformities. 4. Heart involvement includes hypertrophic cardiomyopathy and congestive heart failure. 5. Diabetes mellitus develops in about 10% of patients with Friedreich ataxia.

What is the difference between GLUT-2 and GLUT-4​​​​​​​? Which one is sensitive to / responds to insulin? Where is Glucokinase? Where is Hexokinase? Which one uses a GLUT and which GLUT is used?

GLUT2 facilitates export of glucose from the liver, small intestine, and kidneys into the circulation and also helps to control insulin secretion in the pancreas. GLUT4 is the insulin-sensitive transporter found in skeletal muscle cells and adipocytes. In these cells, the GLUT4 protein is stored in cytoplasmic vesicles. Under the influence of insulin, the transporter protein is incorporated into the cell membrane. An increased number of transporters in the membrane leads to an increased rate of glucose uptake by the cells. GLUT2 has a high Km that allows for glucose sensing; rate of glucose entry is proportional to blood glucose levels. GLUT4 transporters are insulin sensitive, and are found in muscle and adipose tissue to store glucose in muscle and fat. Glucokinase is present only in hepatocytes (liver) and beta cells of pancreas, tissues that need to quickly respond to changes in glucose levels. It uses GLUT2. So it responds to glucose levels, not insulin. It has a high Km, meaning that it does not bind tightly to glucose. Hexokinase is found in most tissues. It does NOT use a GLUT. Compared to glucokinase, hexokinase has a lower Km (binds glucose tightly) and lower Vmax (lower glucose-binding capacity). Notably, the enzyme is not induced by insulin, but does undergo negative feedback inhibition by glucose-6-phosphate. General: Transmembrane carrier proteins that belong to the GLUT family transport glucose by facilitated diffusion (uses a carrier protein but DOES NOT REQUIRE ATP -- that would be counterproductive). These proteins are stereoselective and preferentially catalyze the entrance of D-glucose rather than L-glucose into cells.

++++++++ UWorld +++++++++ What 2 GI hormones stimulate insulin release once a sugary meal is consumed or after oral glucose administration? (This is not activated if glucose is administered IV)

Glucagon-like peptide-1 (GLP-1) and Gastric inhibitory peptide (glucose-dependent insulinotropic peptide, GIP) IMAGE: Oral glucose caused a huge spike in insulin due to GLP-1. (Answer on UWorld) Oral sugar => GLP-1 => Insulin release Incretins are gastrointestinal hormones produced by the gut mucosa that stimulate pancreatic insulin secretion in response to sugar-containing meals. This response is independent of blood glucose levels, and typically occurs prior to any elevation in blood glucose level following a meal. Two hormones with incretin effects are glucagon-like peptide-1 (GLP-1) and gastric inhibitory peptide (glucose-dependent insulinotropic peptide, GIP). Insulin levels will also increase following intravenous administration of glucose due to the sensitivity of the pancreatic beta-cells to increases to blood glucose, but this increase will not be as marked as that seen following oral glucose administration because the effect of incretin is absent.

What metabolic process is clasically inhibited by alcohol, leading to hypoglycemia with excessive drinking? What does it do to the NADH/NAD+ ratio and what effects does this have?

Gluconeogenesis ​​​​​​​Ethanol inhibits gluconeogenesis and can cause hypoglycemia once hepatic glycogen stores are depleted. The metabolism of ethanol by alcohol dehydrogenase and aldehyde dehydrogenase reduces NAD+ to NADH and increases the NADH/NAD+ ratio. This inhibits all other pathways requiring NAD+, including reactions required for gluconeogenesis. In particular, lactate cannot be converted to pyruvate, and instead the reaction is driven from pyruvate toward lactate. In addition, excess NADH inhibits the conversion of malate to oxaloacetate. Malate to Oxaloacetate (gluconeogenesis precursor) requires NAD+. Pyruvate and oxaloacetate are intermediates in gluconeogenesis; therefore, conversion of these molecules to lactate and malate inhibits gluconeogenesis. Sample UWorld Q: A 27-year-old man is brought to the emergency department due to confusion. His roommate says that he has been binge drinking for the last 5 days and probably has had very little to eat. The patient's medical history is significant for alcohol-related seizures 1 year ago. He had been sober until 2 weeks ago, when he started drinking again. The patient's past medical history is otherwise unremarkable. On examination, he responds to voice but does not follow commands. Fingerstick glucose is 35 mg/dL and urine is strongly positive for ketones. Suppression of which of the following is the primary cause of this patient's hypoglycemia? > Gluconeogenesis Alcohol has NO EFFECT on glycogen!

+++++++ High Yield, Always Miss It +++++++ A 5-year-old boy is brought to the emergency department due to 2 days of dark, low-volume urine and decreased energy. The parents say that the boy had abdominal pain, fever, and bloody diarrhea for 4 days, which resolved about 3 days ago without treatment. The day before the onset of symptoms, the patient swam in a lake and ate hamburgers at a family picnic. His vital signs are within normal limits. Physical examination shows pallor but is otherwise normal. He has no peripheral edema or rashes. Laboratory evaluation shows anemia, thrombocytopenia, and elevated blood urea nitrogen and serum creatinine. What is this condition?

Hemolytic Uremic Syndrome!!! - Due to E. coli from the hamburger. Bloody diarrhea. Summary: Hemolytic uremic syndrome (HUS) manifests with acute kidney injury, microangiopathic hemolytic anemia, and thrombocytopenia. Characteristic laboratory abnormalities include decreased hemoglobin and platelet count and increased bleeding time, lactate dehydrogenase, bilirubin, blood urea nitrogen, and creatinine. Most often caused by infection with shiga toxin-producing organisms such as Escherichia coli O157:H7 or Shigella. Hence the hamburger. Shiga toxin enters the circulation from the bowel and induces capillary endothelial damage, resulting in platelet activation with the formation of microthrombi. Platelet consumption causes thrombocytopenia whereas the microthrombi lead to erythrocyte damage (forming schistocytes) and the resultant hemolytic anemia (eg, pallor, weakness, tachycardia). Damage to glomerular endothelial cells also causes acute kidney injury (eg, oliguria/anuria, increased creatinine) in approximately 50% of cases.

++++++++ UWorld +++++++++ Pulmonary Arterial Hypertension: histological appearance and description

Histopathology in pulmonary arterial hypertension typically shows hypertrophy of the pulmonary vascular smooth muscle.

+++++++++++++++++++++++++++++++++++++ What substance (hormone) is responsible for Gestational Diabetes? Why is this a normal thing to develop? Under what conditions does gestational diabetes (abnormal) occur? What energy sources are used by the fetus vs. the mother? What is used for fetal energy if the mother is malnourished?

Human Placental Lactogen (hPL) • Normal: Insulin resistance during pregnancy. • Abnormal: Gestational Diabetes (see paragraph 3 below) hPL essentially blocks the effects of glucose, so w/o insulin, you get: ✔ High blood glucose (for fetus) ✔ Protein degradation to provide AAs (for fetus) ✔ Release of fat stores to increase available FAs (for mother) ✔ Release of ketones if needed (for mother) Fetus is the priority and gets the best energy sources (Glucose and AAs) and insulin resistance occurs so that the fetus gets enough glucose -- no need for mother to store glucose. Summary: Human placental lactogen causes insulin resistance during the 2nd and 3rd trimesters. This elevates serum glucose, which provides adequate nutrition to the growing fetus. Gestational diabetes occurs when the pancreas can't secrete enough compensatory insulin to balance resistance to insulin and serum glucose levels get way too high. i.e., mothers become somewhat resistant to insulin (diabetic-ish) so that glucose stays high enough to support fetus. If it goes too far, it's gestational diabetes. Energy sources during pregnancy: • Mother gets energy from FAs & Ketones • Baby gets best energy: Glucose & Amino Acids hPL mainly stimulates pancreatic beta cell insulin production, but also more (see below and see IMAGE). A physiologic increase in maternal insulin resistance occurs during the second and third trimesters to ensure a readily available supply of glucose and amino acids to the fetus. This increase in insulin resistance is primarily due to the action of human placental lactogen (hPL), a peptide hormone secreted by the syncytiotrophoblast. The rise in insulin resistance leads to increased glucose levels in the maternal circulation. Glucose freely crosses the placenta and is continuously consumed by the fetus for energy. hPL also increases lipolysis in the mother to provide free fatty acids and ketones as energy for the mother (preserving glucose and amino acids for the fetus). Gestational diabetes results when pancreatic function is not sufficient to overcome the pregnancy-related insulin resistance. The average levels of hPL rise with increasing gestational age, reflecting the increasing energy requirements of the growing fetus. Screening for gestational diabetes is therefore more accurate in the third trimester and can be done with an oral glucose challenge and subsequent measurement of serum glucose levels. In cases of maternal malnutrition, the increased ketones can also provide the fetus with energy.

MNEMONIC for the spinal levels of: - Inferior Vena Cava - Esophagus - Aorta Mnem: how many eggs did you eat, and at what time?

I ate 10 eggs at 12 IVC at T8 Esophagus at T10 Aorta at T12

+++++++++++++++++++++++++ What interleukin mediates ASTHMA? (or other atopic / allergic conditions)

IL-5 Classic sputum findings include eosinophils and Charcot-Leyden crystals. Eosinophils are recruited and activated by IL-5 secreted by TH2 type T cells.

++++++++++++++++++++++++++++ Nice table with some MNEMonics for Lysosomal / Glycogen Storage DIseases: • Status of glycogen • Clinical features / hallmarks Lysosomal Storage DIsease Type: I: Von-Gierke (Glucose-6-phosphatase deficiency) II: Pompe (Lysosomal α-1,4-glucosidase deficiency) III: Cori (Debranching enzyme deficiency) IV: Anderson (Branching enzyme deficiency) V: McArdle (Muscle glycogen phosphorylase deficiency) VI: Hers (Hepatic glycogen phosphorylase deficiency)

IMAGE

CREST syndrome stands for: C: R: E: S: T: Due to anti-___ antibody

IMAGE Calcium deposits in skin / anti-Centrometere antibody Raynaud's Esophageal dysmotility Sclerodactyly Telangiectasis anti-Centromere antibody A centromere is what holds sister chromatids together in the middle (at the crossover point of paired chromatids)

++++++++++++++++ KNOW THESE ++++++++++++++++ UWorld diagram -- so everything you need to know! Diabetes drugs: MoA and Side Effects of each: 1. Sulfonureas and Meglitinides 2. Metformin (Biguanides) 3. Pioglitazone (Thiazolidinediones) 4. Exenatide & Liraglutide 5. Sitagliptin & Saxagliptin 6. Acarbose & Migitol 7. Canagliflozin & Dapagliflozin

IMAGE - UWorld

Diagram connecting metabolic pathways: - pyruvate fates and 2 sources - acetyl-coa fates and 2 sources - oxaloacetate fates - role of PEPCK

IMAGE -- be able to draw or visualize how one could jump from one pathway to another via intermediates - Note: "PPS" = ?? -- pyruvate kinase converts PEP to Pyruvate. Pyruvate fates: - can convert to oxalo and enter TCA cycle - can convert to acetyl-coa and enter TCA or FA synthesis - can be produced from glycolysis - can be produced from malate in the TCA cycle Acetyl-CoA: - can enter TCA cycle - can enter FA synthesis - can be produced from FA synthesis intermediates - can be produced from pyruvate Oxaloacetate: - can convert to citrate to continue TCA cycle - can convert to PEP via PEP Carboxykinase (PEPCK) to enter gluconeogenesis PEPCK (Pyruvate Carboxykinase): - converts oxalo to PEP to produce glucose when needed

Function of: 1. Inhibin B 2. DHEA 3. Aromatase 4. 5α-Reductase

Inhibin B • Supresses FSH release • Produced by granulosa cells in the ovary to slow down estrogen production. • Produced by sertoli cells in males to slow sperm production. DHEA - IMAGE • Intermediate in steroid synthesis pathway that produces androgens. • Converted from 17-hydroxypregnenolone. • Turns into Testosterone, which has several fates. Aromatase - IMAGE • Converts testosterone to estradiol / estrogen. • Important for FEMALES. 5α-Reductase - IMAGE • Activates testosterone into DHT. • Important for MALES.

+++++ Saw it a few times in UWorld +++++ What is Kallman Syndrome?

Kallmann syndrome (KS) is a condition that causes hypogonadotropic hypogonadism (HH) and an impaired sense of smell. HH affects the production of the hormones needed for sexual development. It is present from birth and is due to deficiency of gonadotropin-releasing hormone (GnRH).

Klinefelter Syndrome: - Chromosomal abnormality - Testes - Testosterone level / production - Secondary sex characteristics

Klinefelter syndrome (XXY seminiferous tubule dysgenesis) is a common cause of male hypogonadism. Small, firm testes and a decreased serum testosterone level are characteristic. - So small testes and low testosterone Patients may exhibit diminished secondary sexual characteristics. Often have gynecomastia.

+++++++++++++++++++ What is the normal role of Bcl2 and when/why is it inactivated? When it's inactivated, it allows ___ to perform its function of activating ___ for ___.

Lack of Bcl2 allows cytochrome c to leak from inner mitochondrial matrix into cytoplasm to activate caspases. **** Bcl2 inhibits apoptosis until there's DNA damage or cell injury (i.e., signs of a bad cell), and then Bcl-2 is inactivated to allow apoptosis to occur.

+++++ HIGH YIELD, VERY IMPORTANT - RENAL +++++ +++++++++++++++++++ UWorld ++++++++++++++++++++ Know which line on a tubular concentration vs. length along the proximal tubule each of these looks like: • Bicarbonate (HCO3-) • Creatinine • Sodium and Potassium (Na+ and K+) • Glucose and Amino Acids • Urea (nitrogen) Memorize where each is reabsorbed or excreted Also, what is the relevance of urea in the kidneys and its relation to Blood Urea Nitrogen (BUN)

Line 1 represents creatinine, which is freely filtered in the glomerulus, as well as actively secreted and not reabsorbed along the proximal tubule, resulting in a rapidly increasing concentration in the tubular fluid. Line 2 represents urea, which is freely filtered from the glomerular capillaries and is poorly reabsorbed from the proximal tubule, resulting in increasing concentrations along the proximal tubule but less so than with creatinine. It is ultimately secreted in very high concentrations because it is a waste product of metabolism. - Urea is a waste product of protein metabolism (urea cycle in the liver) that should be eliminated by the kidneys. If BUN is high, it means there's a lot of urea in your blood, thus it isn't being excreted by hte kidneys, indicating kidney dysfunction. Line 3 represents sodium or potassium, which is reabsorbed in concentrations approximately equal with water in the proximal tubule, resulting in no concentration change along the proximal tubule. Line 4 represents bicarbonate, which is actively reabsorbed in the proximal tubule due to the activity of carbonic anhydrase along the brush border. This reabsorption causes the concentration of bicarbonate to decrease as fluid runs along the proximal tubule. Line 5 represents glucose or amino acids, which are avidly reabsorbed in the proximal tubule.

3 classic examples of liquefactive necrosis Pathoma Chapter 1 (Cells)

Liquefactive necrosis is when proteolytic enzymes degrade infarcted tissue and turn it into liquid. 1. BRAIN: proteolytic enzymes from microglial cells liquefy the brain. 2. PANCREATITIS: proteolytic enzymes from the pancreas (pancreatic enzymes) liquefy pancreatic tissue. 3. Abscesses: proteolytic enzymes from neutrophils liquefy the affected tissue. Ex: Liver abscess. NOTE: Liquefactive necrosis is the ONLY type of necrosis that affects the BRAIN.

The hallmark of cellular death is ___ Define: - Pyknosis - Karyorrhexis - Karyolysis Pathoma Chapter 1 (Cells)

Loss of nucleus = cell death. If a cell has no nucleus, it is no longer alive (can't make DNA, proteins, etc.) Nuclear loss occurs via 3 steps: 1. Pyknosis: condensation of chromatin (i.e., chromaatin condenses) in the nucleus of a cell undergoing necrosis or apoptosis. 2. Karyorrhexis: fragmentation of the nucleus of a dying cell whereby its chromatin is distributed irregularly throughout the cytoplasm. 3. Karyolysis: dissolution of nucleus (i.e., nucleus dissolves).

Thyroid nodule in a patient with history of pheochromocytoma and a family history of thyroid cancer = which type of thyroid cancer? Histology?

MEDULLARY thyroid cancer MEN2 mutation: - Medullary thyroid cancer - Pheochomocytoma - Parathyroid cancer (2A) or Marfinoid habitus with mucosal neuromas (2B) Histology: Nests of polygonal cells with Congo red-positive deposits Approximately 20% of medullary thyroid cancers are familial, occurring as part of MEN2 or familial medullary thyroid cancer syndrome due to germ-line mutations of the RET proto-oncogene. Medullary thyroid cancer is a neuroendocrine tumor that arises from parafollicular calcitonin-secreting C cells. Nests or sheets of polygonal or spindle-shaped cells with extracellular amyloid deposits are seen microscopically. These amyloid deposits (black arrow in the image above) are derived from calcitonin secreted by the neoplastic C cells and stain with Congo red. Despite overproduction of calcitonin, hypocalcemia is not a prominent feature.

++++++++++++++++++++++++++++ ​​​​​​​If a patient has any type of aphasia -- wernicke's or broca's -- there was a stroke in which cerebral artery?

MIDDLE cerebral artery

++++++ From YouTube NBME 20 Walkthrough +++++ If there are a bunch of random symptoms, but it mentions that the patient's female relatives (mother, grandmother, sister, etc.) are also affected, look for what in the answer choices?

MITOCHONDRIA -- anything to do with that. MNEM: Mitochondrial = Maternal Mitochondrial inheritance is transmitted ONLY from the Mother. All offspring (males or females) of the affected female can show signs of the disease. So look for a female as the original source (e.g., in IMAGE it was the maternal grandmother). e.g., (IMAGE) MELAS syndrome (Mitochondrial Encephalopathy, Lactic Acidosis, Stroke-like episodes) So in that sample problem, you didn't even have to know what the disease was. Just notice the inheritance pattern!

++++++++++++ High Yield ++++++++++++++ Chediak-Higashi Syndrome: Typical presentation (PATHOMA - very good explanation) 1- Pathophysiology: The underlying problem is defective ___, which causes impaired formation of ___. 2- Increased risk of ___ infections 3- What's the state of neutrophils (% neutrophils on leukocyte differential)? What happens to them? 4- What happens to the granules inside of neutrophils? (granules are the pods in neutrophils that hold the hydrolytic stuff) 5- What happens to platelets? i.e., What is the hematological abnormality of these patients? 6- What sensory/nerve issue is common? 7- Hair 8- Inheritance pattern

MedBullets Stem: A 3-year-old boy is brought to his pediatrician after he slipped and scraped his knees on asphalt. His knees are severely infected, with visible pus. He has a history of bleeding gums and easy bruising. On physical exam, he is febrile, his retina is pale, and his hair is very blonde, and some hair is noted to be silver. 1- Due to a defect in microtubules, cell contents are unable to move around the cell. This leads to impaired phagolysosome formation - phagocytes can't move towards lysosomes to fuse in the neutrophils, so there is reduced phagocytosis. Neutrophils eat pathogens, but they can;t be destroyed by lysosome's hydrolytic enzymes. - Microtubule (cell trafficking protein) defect is the underlying cause of ALL the problems in this disease, as described below. Microtubules act like railroads inside cells, moving cell contents around. All symptoms of this disease are related to something not being able to move to its target location within cells. 2- Increased risk of pyogenic infections -- form lots of PUS. Particularly common are Staph / Strep. 3- Neutropenia (low % neutrophils on leuk differential). Due to intramedullary destruction of neutrophils (i.e., neutrophils die inside the bone marrow). Microtubule defect means DNA can't move around and neutrophils can't divide to produce more. 4- GIANT granules in neutrophils because they fuse after leaving the golgi apparatus due to defect in microtubules (can't move around cell after leaving golgi, so they fuse). See IMAGE - you can see the granules. 5- Abnormal dense granules in platelets causes defective primary hemostasis -- increased bleeding time, etc. Platelet problem, 6- Peripheral neuropathy is common -- sensory issues in peripheral limbs. Again, due to microtubule dysfunction. Peripheral nerves are one long cell. Without microtubules, important nutrients can't reach the ends of these nerves, so you get peripheral neuropathy. 7- Albinism. Hair is very blonde and often silver. Again, due to microtubule dysfunction - melanin can't leave melanocytes to go into epidermal keratinocytes if microtubules aren't there. 8- Autosomal Recessive

Which glomerular disease is seen in patients with LUPUS? What will be seen on: - Light microscopy - Immunofluorescence - Electron microscopy

Membranous Glomerulopathy Immune complex deposition MG is caused by immune-complex deposition in the subepithelial portion of the glomerular capillary wall. Light microscopy shows diffuse thickening of the glomerular basement membrane (GBM) without an increase in glomerular cellularity. - vs. membranoproliferative glomerulonephritis, which has GBM thickening and increased number of cells (tightly packed). Immunofluorescence reveals granular deposits of IgG and C3 along the GBM Electron microscopy demonstrates irregular, electron-dense immune deposits located between the GBM and epithelial cells. Protrusion of the GBM through the deposits resemble spikes and domes when stained with a silver stain:

++++++++ High Yield, Often Missed in UWorld ++++++++ Diagnosis if a patient has these symptoms: - Normocytic anemia - Back pain - Renal failure - Hypercalcemia (constipation, muscle weakness) - Constitutional symptoms: fatigue, weight loss State what causes each of those features. UWorld Example: A 64-year-old man comes to the office due to persistent back pain, constipation, and easy fatigability for the last several months. Blood pressure is 115/75 mm Hg and pulse is 88/min. The patient has dry mucous membranes. Laboratory results are as follows: - Hemoglobin: 8.6 g/dL - Mean corpuscular volume: 92 fL - Blood urea nitrogen: 68 mg/dL - Creatinine: 3.8 mg/dL - Total protein: 8.9 g/dL - Albumin: 3.5 g/dL Renal biopsy is performed and light microscopy shows atrophic tubules, many of which contain large, obstructing, waxy casts that stain intensely with eosin.

Multiple Myeloma It should be suspected in elderly patients with any combination of hypercalcemia (causes constipation), normocytic anemia (causes fatigue), bone pain (often in the back and ribs due to lytic lesions), elevated gamma gap (due to the presence of large amounts of monoclonal proteins), or renal failure. Hypercalcemia is due to bone degradation due to cytokine production that activates RANK receptor on osteoclasts (thus, osteoclasts are activated and degrade bone). Renal failure in MM is often caused by light chain cast nephropathy (MM produces IgG or IgA that deposit). Free light chains (Bence Jones proteins) are filtered by the glomerulus in small amounts and then reabsorbed in the tubules. When levels exceed reabsorptive capacity, light chains precipitate with Tamm-Horsfall protein and form casts that cause tubular obstruction and epithelial injury, leading to impaired renal function. On light microscopy, numerous large, glassy eosinophilic casts are seen.

Myasthenia Gravis vs. Lambert-Eaton Myasthenic Syndrome

Myasthenia gravis is caused by postsynaptic anti-Ach receptor autoantibodies and is characterized by episodic weakness (WORSE with use) that initially affects the ocular/bulbar (facial) musculature. Lambert-Eaton myasthenic syndrome is a paraneoplastic condition causing weakness (BETTER with use) in the extremities. It is caused by autoantibodies to presynaptic calcium channels. Light microscopy of muscle biopsy specimens is normal in these conditions, as opposed to polymyositis and dermatomyositis (which have CD8+ infiltration into muscles).

+++++++++++++++++++ If an HIV patient really sounds like they have tuberculosis, including granulomas on histology, but have a negative TB test, what is the classic pathogen?

Mycobacterium Avium IMAGE: Epithelioid / foamy histiocyte Subacute systemic symptoms (eg, fever, night sweats, weight loss, weakness), lymphadenopathy, hepatosplenomegaly, elevated alkaline phosphatase, and intracellular acid-fast bacteria raise strong suspicion for disseAC is an infection caused by the nontuberculous mycobacteria M avium and Mycobacterium intracellulare. Although these infections can occur in both immunocompetent and immunosuppressed hosts, most cases arise in patients with untreated AIDS who have CD4 counts <50/mm3. MAC organisms are acquired by ingestion or inhalation. They are phagocytosed by macrophages but initially evade destruction due to microbial virulence factors that prevent phagolysosome formation. In healthy individuals, the infection is controlled with the cell-mediated immune response. However, in patients with advanced AIDS, the body is unable to generate sufficient CD4-mediated cytokines (eg, interferon-gamma) to activate macrophages, which allows the pathogen to spread through the bloodstream and reticuloendothelial system.

++++++++++++++++++++++++++++++++++++++++++++++ +++++ RENAL EXCRETION vs REABSORPTION +++++ ++++++++++++++++++++++++++++++++++++++++++++++ (On a graph of Tubules:Plasma concentration ratio vs. Length along the collecting ducts) For each substance, know: (a) Whether it is reabsorbed or excreted (b) WHERE in the tubules it is most / fastest reabsorbed or excreted (c) Where in the tubules the concentration in the urine/filtrate is the highest (d) Where in the tubules the concentration in the urine/filtrate is the lowest 1. PAH (para-aminohippuric acid) 2. Creatinine 3. Inulin & Mannitol 4. Urea (BUN) (Nitrogen) 5. Sodium & Chloride 6. Glucose 7. Potassium Where is water reabsorbed the most?

Notes • Excreted = going into urine • Reabsorbed = going into blood to stay in body • 1/2/3 - PAH (para-aminohippuric acid), Creatinine, Inulin, and Mannitol should all be completely excreted. PAH is not made by the body, but injected in studies to measure GFR because it should completely be peed / filtered out. 1. PAH • Excreted fastest in the proximal tubule and continues to go into the urine throughout the nephron. • As you can see, PAH is excreted faster than anything -- even faster than inulin. It is the perfect measure of GFR. 2. Creatinine • Same pattern as PAH: excreted fastest in the proximal tubule and continue to be excreted into urine throughout the nephron. 3. Inulin & Mannitol • Same pattern as PAH and especially Cr: excreted fastest in the proximal tubule and continue to be excreted into urine throughout the nephron. 4. Urea - BUN - Nitrogen • Excreted fastest in the LOOP and continues to be excreted less rapidly in the DCT and CD 5 Na+ & Cl- • Excreted a little in the descending loop (hypertonicity of medulla) • Reabsorbed rapidly into the blood in the ascending loop • Continues to slowly increase in the urine throughout the rest of the nephron. 6. Glucose • Rapidly reabsorbed right away in the proximal tubule. Body wants it back right away. 7. Potassium • Most leaves urine in the proximal tubule • More leaves urine in the thick ascending limb • In the DCT and CD (Aldo receptor), a ton of K+ is dumped back into the urine. • UW: K+ is freely filtered by the glomeruli and is mostly reabsorbed in the proximal tubule and loop of Henle. As such, the late distal and cortical collecting tubules are the primary sites for regulation of K+ excretion in the urine. K+ depletion stimulates α-intercalated cells to reabsorb extra potassium; principal cells secrete K+ under conditions of increased K+ load. Water is reabsorbed mostly in the proximal tubule, and continues to be reabsorbed in the descending limb to establish high osmolality inside the tubules in the medulla. AQP2 channels are present in the collecting duct and reabsorb water.

+++++ "Very, Very High Yield +++++ How does CCL4 (carbon tetrachloride, free radical) lead to fatty liver disease? Pathoma Chapter 1 (Cells)

Nutshell: Blocks protein synthesis in the liver, including apolipoproteins, and without apolipoproteins, fat builds up in the liver. CCl4 is a solvent used in dry cleaning CCl4 is converted to CCl3• (free radical) by P450 in the liver, resulting in cellular injury of hepatocytes including RER swelling. Swollen RER can't produce apolipoproteins, so fat builds up in the liver, causing fatty liver disease. IMAGE: Fatty liver change

In a Patent Ductus Arteriosus, what is the primary blood flow abnormality?

OXYGENATED blood flows from the aorta to the pulmonary artery, so the pulmonary artery will have a higher-than-normal O2 content. In patients with patent ductus arteriosus, left-to-right shunting of oxygenated blood from the aorta into the pulmonary artery results in a higher-than-expected oxygen concentration in the pulmonary artery. Oxygen saturation in the left and right heart chambers is unchanged.

FAS ligand does what? It binds to CD__ What's the classic (and most commonly tested) way that the FAS ligand pathway is used? Pathoma Chapter 1 (Cells)

One of the pathways to apoptosis -- extrinsic receptor-ligand pathway. FAS ligand binds to CD95 (FAS death receptor) on the surface of target cells, activating caspases. - Caspases cause apoptosis by (a) activating proteases which degrade the cytoskeleton of the cell membrane and (b) activating endonucleases that break down DNA. This is the mechanism of negative selection of pre-T-cells (aka thymocytes) in the thymus. If a T-cell binds self-antigen too strongly, the FAS ligand pathway is activated to kill that T-cell. ^ "Very high yield way to test you on FAS ligand

If a bacteria (G-) produces extended-spectrum beta-lactamase (ESBL), what is the most likely mechanism by which it developed this? What is the antibiotic of choice for these species?

PLASMIDS coding for ESBL; conjugated between G- bacteria. Carbapenems -- nothing else will work; ESBL even kills cephalosporins. Extended-spectrum beta-lactamases can be produced by gram-negative bacteria, rendering cephalosporins and other beta-lactam antibiotics inactive. These genes can be transmitted between organisms through plasmid conjugation. ESBL enzymes can inactivate extended-spectrum penicillins and cephalosporins (including third- and fourth-generation cephalosporins) and monobactams (aztreonam). Genes encoding these enzymes are often located on plasmids and therefore can be transferred between organisms and between different species through conjugation. Some have been incorporated into bacterial chromosomes. Carbapenems (eg, imipenem) are the treatment of choice for ESBL-producing organisms (although unfortunately, organisms with carbapenem resistance have emerged). NOT: - Porin mutations -- porin mutations can confer penicillin and aminoglycoside resistance and are particularly important in gram-negative organisms such as Pseudomonas. - Penicillin-binding protein alterations -- that's the mechanism that leads to methicillin resistance in Staphylococcus aureus.

High yield antibiotic resistance mechanisms - name how bacteria can beceome resistant to: - Penicillins (penicillin, aminopenicillins, cephalosporins, etc.) - Vancomycin - Quinolones / FQs - Aminoglycosides - Tetracycline - Rifamycins

Penicillins Beta-lactamase, ESBL (plasmids coding for extended spectrum beta lactamase) Mutated Penicillin Binding Protein Mutated porin protein Vancomycin Mutated peptidoglycan cell wall Impaired influx/increased efflux Quinolones Mutated DNA gyrase Impaired influx/increased efflux Aminoglycosides Aminoglycoside-modifying enzymes Mutated ribosomal subunit protein Mutated porin protein Tetracyclines Impaired influx/increased efflux Inactivated enzyme Rifamycins Mutated RNA polymerase ESBL = extended-spectrum beta-lactamase; PBP = penicillin-binding protein.

What is the most common cause of Budd-Chiari Syndrome? Budd-Chiari Syndrome involves hypoxia due to ... Pathoma Chapter 1 (Cells)

Polycythemia Vera is the most common cause. - Lupus is another common cause. It's due to decreased venous drainage from the liver (as opposed to decreased blood delivery). New oxygenated blood can't perfuse congested liver very well.

+++++++++++++++ UWorld +++++++++++++++ A 44-year-old man comes to the clinic due to increasing fatigue, trouble sleeping, and palpitations. He has lost 9 kg (20 lb) over the last year despite eating well. The patient says he is under a lot of pressure at work but cannot think of any other precipitating factors for his insomnia. He has no other medical problems and takes no medications. The patient does not use tobacco, alcohol, or illicit drugs. His mother has a history of a thyroid problem. Blood pressure is 140/80 mm Hg and pulse is 108/min. On physical examination, the thyroid is diffusely enlarged. His serum free thyroxine level is elevated and TSH level is decreased. He is found to have a positive assay for thyrotropin receptor antibodies. If present, which of the following additional findings would be most specific to the underlying cause of this patient's hyperthyroidism? A. Atrial fibrillation B. Decreased bone mineral density C. Heat intolerance D. Skin thickening and induration E. Tremor of the outstretched hands

QID: 623 D. Skin thickening and induration It's referring to pretibial myxedema, a skin condition characterized by red, swollen skin, usually on the shins and tops of the feet. The texture of the affected skin may be similar to that of an orange peel -- see IMAGE It's specific to Grave's Disease. The stimulating antibody directly causes thickening of that skin as well as the opthalmopathy. Summary: Pretibial myxedema and Graves ophthalmopathy are specific features of Graves disease. They are caused by an autoimmune response directed against the TSH receptor that results in the accumulation of glycosaminoglycans within the affected tissues. This patient's positive serum assay for thyrotropin receptor antibodies (TRAb) confirms the diagnosis of Graves disease. TRAb bind and activate the TSH receptor, causing increased release of thyroid hormone by the thyroid gland, which is responsible for the general symptoms of hyperthyroidism (eg, fatigue, palpitations, weight loss, and insomnia). In addition to the thyroid, the TSH receptor antigen is present on fibroblasts, adipocytes, and other tissues. Thyroid dermopathy is caused by stimulation of fibroblasts by TRAb and activated T-cells, leading to excess production of glycosaminoglycans and adipogenesis. This leads to induration and thickening of the skin over the shins (pretibial myxedema, as shown above). Graves ophthalmopathy occurs in a similar manner, with expansion of the retro-orbital tissues displacing the eyes forward. Because these processes are directly related to TRAb, they have a high specificity for Graves disease.

++++++++++++++++++ What are the states of PTH, Calcium, and Phosphate in osteoporosis?

QID: 982 NormalIn primary osteoporosis (ie, osteoporosis that is not due to an underlying medical disorder), serum calcium, phosphorus, and parathyroid hormone (PTH) levels are typically in the normal range. That means it's possible to have normal blood calcium levels and still be losing bone. However, other bone diseases may show elevated results. Osteoporosis is characterized by decreased bone strength resulting from low bone mass and microarchitectural deterioration of bone tissue, but calcium levels are normal. See IMAGE: A 68-year-old Caucasian woman comes to the emergency department due to several hours of severe upper back pain. The patient developed the pain after experiencing a sudden jolt while driving over a pothole. She has no previous history of back pain or major trauma and has not seen a doctor in many years. The patient is retired and lives a sedentary lifestyle. She drinks a glass of wine daily and eats a healthy, balanced diet. BMI is 18.4 kg/m2. On examination, there is point tenderness over the T10 vertebra. Neurologic examination is unremarkable. X-ray of the spine reveals a T10 compression fracture. On the graph, area C represent the normal serum concentrations of calcium and parathyroid hormone. Which of the following areas most likely corresponds to this patient's current metabolic state? Answer: area C​​​​​​​ in IMAGE

++++++++++++++++ VERY IMPORTANT ++++++++++++++++ For nerves and neurons: 1. Which side is negative during the resting state (RMP) and what ion maintains this? 2. What ion flows into the nerve / neuron to cause depolarization so the nerve / neuron can fire? 3. After firing, what ion flows out of the nerve / neuron to restore the RMP (gradient)?

Resting State: Inside is NEGATIVE relative to outside, which is the RMP. This is maintained only by the flow of potassium. Summary: - Depolarization: Sodium flows INTO the nerve to depolarize it for an action potential. - Repolarization: Potassium flows OUT of the nerve to restore the membrane potential for the next firing. 1. Depolarization: During depolarization, sodium flows IN (via voltage gated sodium channels) due to an electrical stimulus. As sodium rushes into the cell, the positive sodium ions raise the charge inside the cell from negative to positive. 2. Return to Normal: Once the cell has been depolarized, the sodium channels close. The high intracellular positive charge causes potassium channels to open, K+ ions now move down their electrochemical gradient out of the cell. As the K+ moves out of the cell the membrane potential falls and starts to approach the resting potential. Typically, repolarization overshoots the resting membrane potential, making the membrane potential too negative. This is known as hyperpolarization. Pufferfish toxin (parasthesias after eating fish, esp. at a Japanese restaurant) prevents depolarization as it blocks sodium channels.

+++++ Very Very High Yield +++++ The hallmark of irreversible cellular injury is ___ ___. How does this occur and what are the high yield consequences? "Easy Exam Questions" Pathoma Chapter 1 (Cells)

Reversible cell injury eventually progresses to irreversible cell injury. The hallmark of irreversible cellular injury is MEMBRANE DAMAGE. There's no going back if the membrane is lost. +++ Easy Test Q's +++: Plasma membrane damage results in: 1. Cytosolic enzymes leaking into the serum (e.g., cardiac troponin) - when you get a troponin level, you're really asking "is there irreversible damage to the cardiac cells?" 2. Additional calcium entering the cell (Ca2+ is a major enzyme activator; don't want too much of it inside the cell). Mitochondrial membrane damage results in: 1. Loss of electron transport chain => Loss of ATP production => dead cell 2. Cytochrome c leakage into cytosol (Cyt c activates apoptosis) Lysosome membrane damage results in hydrolytic enzymes leaking into the cytosol, which are then activated by the high intracellular calcium. Cause significant damage to the cell.

+++++++++ HAVE THIS DOWN +++++++++ Lupus / SLE: Clinical Symptoms: - Constitutional - Joints - Skin - Serosal surfaces (lung pleura, pericardium, and peritoneum) - Hemostasis -- increased risk of... - Neurologic Labs - Blood: RBCs, Plts, Leukocytes - Complement: C_ & C_ deficiencies - Antibodies: 1 sensitive, 2 specific - Renal effects: elevated ___ in urine and elevated ___

See IMAGE

+++++++++++++++++++++ +++++++ UWorld ++++++ Cardiac Tampnade: 1. 2 Etiologies / definition 2. Classic BUZZword clinical signs (Beck's Triad​​​​​​​) 3. What phenomenon will ECG show? (BUZZ) 4. What will happen with their blood pressure? (BUZZ) 5. Classic description of heart auscultation (BUZZ) 6. CXR will show what heart abnormality? (BUZZ) 7. How does it physically affect the heart? 8. Therefore, what changes will occur in the: • Central venous pressure • RA cavity size • Left atrial pressure • Stroke volume

See IMAGE Central venous pressure: Increased RA cavity size: Decreased (compressed) Left atrial pressure: Increased Stroke volume: Decreased Cardiac tamponade results from an accumulation of fluid within the relatively noncompliant pericardium, leading to an increase in pericardial pressure. The increased pericardial pressure compresses the relatively low-pressure, right-sided heart chambers and restricts diastolic filling of the right side of the heart to cause obstructive shock. In addition to Beck's triad (ie, hypotension, distant heart sounds, jugular venous distension), other common signs of tamponade include an absent point of maximum impulse and pulsus paradoxus (ie, >10 mm Hg drop in systolic blood pressure with inspiration). UWorld question stem: (asked about cardiac parameters) A 64-year-old man comes to the emergency department due to worsening dizziness and shortness of breath for the past several days. Blood pressure is 85/45 mm Hg, pulse is 122/min and regular, and respirations are 22/min. Pulse oximetry is 94% on room air. There are undulations (changes) in blood pressure at different phases of respiration. On physical examination, the point of maximal impulse is not palpable, and heart sounds are distant. Chest x-ray reveals diffuse pulmonary metastatic disease and new enlargement of the cardiac silhouette.

Lung Apex vs. Base: - Where is ventillation highest? - Where is perfusion highest? - Where is V/Q the highest / lowest? - Where is PO2 highest? - Where is PCO2 highest?

See Uworld card about it. Both V and Q are highest in the base of the lungs, where most exchange occurs. V/Q drops in the base because perfusion (Q) increases way more than ventillation (V) in the base of the lungs. Ventilation (V) refers to the flow of inhaled air into and out of the alveoli, while Perfusion (Q) refers to the flow of blood to alveolar capillaries. Individual alveoli have variable degrees of ventilation and perfusion in different regions of the lungs.

++++++++++++ HAVE THESE DOWN ++++++++++++ For each dyslipidemia, based on the deficient protein, name the elevated lipoprotein and the unique clinical findings and future risks: 1. Lipoprotein lipase (LPL) or Apo C-II deficiency 2. LDL Receptor or Apo B-100 deficiency 3. Apo E deficiency E.g., name the deficiency in which you would see each: • Acute ancreatitis • SKIN xanthomas • TENDON xanthomas & Xanthelasmas (eyes) • PALMAR xanthomas • Coronary Artery Disease (e.g., MIs) (2 of them)

See and memorize IMAGE Key distinguishing features: • Acute Pancreatitis: LPL or Apo C-II deficiency • SKIN xanthomas: LPL or Apo C-IIdeficiency • TENDON xanthomas & Xanthelasmas: LDL receptor or Apo B-100 deficiency • PALMAR xanthomas: Apo E deficiency • Coronary Artery Disease (e.g., MIs): LDL receptor, Apo B-100, or Apo E deficiencies Sample UWorld Q: A 6-year-old boy is brought to the emergency department after a traumatic fall from his bicycle. Physical examination shows a large laceration over his left leg that is irrigated and closed with sutures. While he is receiving care, a routine blood draw shows milky plasma that forms a creamy-appearing supernatant upon standing. Further testing shows that his plasma lipoprotein lipase activity measured after intravenous heparin administration is substantially lower than normal. If his condition remains untreated, this patient is most likely to develop which of the following features? - Answer: Acute Pancreatitis > because LPL is deficient > NOT Myocardial Infarction, Tendon xanthomas, or Xanthelasmas -- so really know these

+++++++++ High Yield Now +++++++++ SPIKES protocol: Rules for delivering bad news - IN ORDER: • Setting the stage • Perception • Invite • Knowledge • Empathetic Response • Summarize

Set the stage - First, you need to set the stage. Arrange a one-on-one interview with patient and/or family and make efforts for esuring privacy. - Involve significant others - Avoid interruptions - Provide information about the expected time frame of the interview to the patient (how long this will take). Patient/Family's Perception of Disease - Determine the patient/family's perception of the situation - Frame it as an open-ended question - Ask the patient to explain illness/therapy/prognosis in their own words - e.g., if a pt dies from a lupus complication, when calling the family, the correct fist step is to ask what they know about the patient's lupus: "What do you know so far about your family members' condition up to this point?" Invitation - Invite patient to talk about certain topics - e.g.,"Shall I share the results of the scan with you now?" - e.g., "Is this a good time to tell you what I believe is happening?" Knowledge - When it is time to break the news, patients and families benefit from a brief summary of what we knew (or thought we knew), what we hoped for, and finally, what we have now learned. - Warn the patient that bad news/prognosis is coming before giving knowledge and information - Avoid technical terms; use of short and precise sentences - Avoid excessive bluntness - Most patients, especially during emotionally charged times, are best served with clear, nonmedical language. Then explain what the bad news means. If you pause after relating what the findings are, the patient and family may ask what the findings mean. In this way you have allowed them to once again invite you to tell more. Emotions / Empathetic Response - Identify emotional triggers and address the patient's emotions with empathic responses (nonverbal communication) - Speak words that acknowledge that your patient is feeling something. The response may be a statement or question; go with what feels right at the time. For example: > "This must be very hard news for you to hear." "I imagine this is very disappointing." > "Is this a big surprise, or did you kind of expect this?" - And our own feelings count as well: > "I'm so sorry, and I am really disappointed, too. I was also hoping we'd have more time." - Try not to immediately shift away from the uncomfortable silence, the sadness, or the tears. This is how we process tragedy. Summarize Summarize and plan strategy (treatment options, prognosis, next consultation, offering palliative support, inquiring about patient's needs and wishes)

+++++ Very Very High Yield +++++ The hallmark of reversible cellular injury is ___ ___. How does this occur and what are the high yield consequences? Pathoma Chapter 1 (Cells)

The hallmark of reversible cellular injury is CELLULAR SWELLING. Mechanism: Hypoxia => impaired oxidative phosphorylation => inadequate ATP supply. Lack of ATP impairs: 1) Na/K Pump: Na+ gets stuck inside the cell. Water follows Na+. Water buildup in cell => cellular swelling. 2) Ca2+ Pump: Purpose is to keep Ca2+ out of cell. Without ATP, Ca2+ stays in cell and is a major enzyme activator. 3) Aerobic Glycolysis: Lactate builds up from anaerobic glycolysis and makes the cytosol to acidic, which denatures proteins and precipitates DNA. >> High Yield Features << 1. Loss of Microvilli (mainly in GI tract): cell swells so much that distinct villi on cell are lost. 2. Membrane Blebbing: Membrane is still intact, but has blebs.

++++++++++++++++++ Embryology - UWorld The metanephros (aka metanephric blastema) gives rise to what structures? The ureteric bud (aka metanephric diverticulum) gives rise to what structures?

The metanephros (metanephric blastema) gives rise to the: • Glomeruli • Bowman's space • Proximal tubules • Loop of Henle • Distal convoluted tubules The ureteric bud (metanephric diverticulum) becomes the collecting system of the kidney, including the: • Collecting tubules • Collecting duct • Major and minor calyces • Renal pelvis • Ureters Question: If a toxic insult occurs during early fetal development that selectively inhibits the renal structures formed by the metanephric blastema, which of the following adult derivatives will fail to develop? - Answer: Distal convoluted tubules - NOT collecting ducts, major/minor calyces, or renal pelvis Embryonic kidney development involves the sequential formation of 3 sets of nephric systems termed the pronephros, mesonephros, and metanephros. The urinary structures formed during these stages are derived from the nephrogenic cord which develops from the urogenital ridge (intermediate mesoderm): 1. The pronephros forms first and later completely regresses. 2. The mesonephros forms next from the midportion of the nephrogenic cord. (a) In males, it persists as the Wolffian ducts, forming the ductus deferens and epididymis. (b) In females, the mesonephros regresses and becomes vestigial Gartner's ducts. 3. The metanephros forms last from the caudal end of the nephrogenic cord.It gives rise to the glomeruli, Bowman's space, proximal tubules, the loop of Henle, and distal convoluted tubules.

+++++++++++ Need to Know +++++++++++ With any autoimmune disease, you need to consider the possibility of ...

The patient having another autoimmune disease

A 3-year-old girl is brought to the office due to 2 days of fever and rash. Her mother says the patient has also been refusing to eat or drink. She has no prior medical conditions and is up to date with recommended vaccinations. None of the family members have had recent febrile illness, but the patient recently started attending day care. Temperature is 38.3 C (101 F). Physical examination shows multiple small vesicles and ulcers with an erythematous base on the buccal mucosa and tongue. There are similar vesicular lesions on the distal extremities. What is the diagnosis and most likely underlying cause of this patient's rash?

UWorld answer: Disseminated enteroviral infection​​​​​​​ This patient's vesicular rash on the buccal mucosa, tongue, and distal extremities likely indicates hand-foot-and-mouth disease (HFMD), a common childhood illness caused by species of Enterovirus (eg, Coxsackievirus). Transmission largely occurs via the fecal-oral route, and outbreaks are common in day cares and elementary schools. The virus initially replicates in gastrointestinal lymphatic tissue and subsequently disseminates through the reticuloendothelial system (macrophages) and bloodstream to other organs (eg, heart, liver, brain, skin). Patients generally develop low-grade fever and the following mucocutaneous findings: - Oral enanthem - painful, erythematous vesicles and ulcers on the tongue and buccal mucosa, which may lead to refusal to eat or drink - Skin exanthem - maculopapular or vesicular lesions on the hands, feet, and extremities

Pseudogout: - Pain and erythema is usually in what joint? (vs gout) - Crystals have [positive/negative] birefingence under polarized light? (vs gout) - Crystals are composed of ___ (vs gout). - Crystals have what shape? (vs gout)

Usually the knee (vs. toe in gout) Rhomboid-shaped, positively birefringent crystals on joint fluid aspirate. - vs. gout: needle shaped, negative birefringence Crystals are made of CALCIUM PYROPHOSPHATE - vs. gout - urate and monosodium urate

What is the difference between Ventillation (V) and Perfusion (Q)? What is the main cause of V/Q mismatches?

Ventilation (V) refers to the flow of air into and out of the alveoli, while Perfusion (Q) refers to the flow of blood to alveolar capillaries. Individual alveoli have variable degrees of ventilation and perfusion in different regions of the lungs. Pulmonary Embolisms (DVTs) are the main cause of V/Q mismatches. They cause a perfusion defect in which some alveoli are ventilated but not perfused (which is the case for all V/Q mismatches). This is because blood stops going to parts of the lungs that aren't working, but inhaled air still goes there. V/Q mismatches are caused by anything that increases physiological dead space, including DVTs and lung tumors that obstruct blood flow in the lungs.

What kind of salivary gland tumor has germinal centers and lymphocytes on bx and is highly associated with smoking? (MNEM)

Warthin Tumor MNEM: WARiors from GERMany love SMOKING

Achalasia

absence of peristalsis of the lower esophagus resulting in difficulty swallowing, regurgitation, and sometimes pain LES doesn't relax and there's decreased esophageal motility / peristalsis. Due to damage to ganglion cells from Chagas disease (parasite) or another infection Presents with DYSPHAGIA to both Solids and Liquids. CLASSIC: Bird's Beak appearance -- dilated esophagus with stricture below it. See IMAGE. HIGH YEILD: HIGH LES Pressure

Appropriate compensatory PaCO2 or bicarbonate changes in acid-base disorders: 1. Metabolic Acidosis (acute or chronic) - expected compensatory PaCO2 formula -- Winter's formula that determines if there's appropriate respiratory compensation. - e.g., if bicarbonate is 14 and there's appropriate respiratory compensation, PCO2 will = ___ + 2. Otherwise, uncompensated, which means it's ... 2. Metabolic alkalosis (acute or chronic) - PCO2 should increase by __mmHg per every 10 mEq/L increase in Bicarbonate 3. Respiratory acidosis (chronic only) - Bicarb should increase by ___ mEq/L per every 10 mm Hg ↑ in PaCO2 - (but this happens over days) 4. Respiratory alkalosis (chronic only) - Bicarbonate should decrease by ~ __ mEq/L per every 10 mm Hg ↓ in PaCO2 - (but this happens over days)

e.g., if pH is low and Bicarb is only 14, it's metabolic acidosis. Use Winter's formula: This patient's serum HCO3− of 14 mEq/L should be compensated by a PaCO2 in the range of 27-31 mm Hg, but his PaCO2 is 40, which is higher than expected, indicating that he has a mixed acid-base disturbance consisting of metabolic and respiratory acidoses. Severe diabetic ketoacidosis can cause pulmonary edema, respiratory fatigue, and decreased mental status, which may lead to hypoventilation and subsequent hypercarbic respiratory failure.

+++++++++ Try to Memorize These +++++++++ Name the (a) Muscles (b) Cranial Nerves (c) Arteries (d) Body parts that are derived from each Pharyngeal / Branchial ARCH: (Pharyngeal = Branchial) Pharyngeal / Branchial Arch: - 1 - 2 - 3 - 4 / 5

https://www.youtube.com/watch?v=snarUr9LmJk&ab_channel=baronerocks - Only decent MNEM I found, but rough homemade video. If you can't remember them, watch it. - His MNEM: 1- Make 2- Some 3- Important 4/5: Shtuff MedBullets page on it: "Branchial Apparatus" https://step1.medbullets.com/embryology/103018/branchial-apparatus IMAGE: Simplified version Arches 4 & 5 do the SAME thing

List of common free radicals Pathological generation of free radicals from: - ionizing radiation - inflammation - metals - drugs and chemicals Which 3 vitamins are antioxidants? High Yield: What are the 3 enzymes that are important for the elimination of free radicals? Pathoma Chapter 1 (Cells)

naturally occurring, highly reactive chemicals containing an odd number of electrons that form in the presence of oxygen (e.g., some are formed during oxidative phosphorylation) Causes of free radical generation • radiation exposure • P450 metabolism of drugs (e.g., acetaminophen) generates free radicals • redox reactions • naturally as part of oxidative ATP generation • nitric oxide • metals - e.g., copper and iron -- IMPORTANT -- see section at bottom. • leukocyte oxidative burst • reperfusion after anoxia - a major cause of injury after thrombolytic therapy (i.e., reperfusion injury) • carbon tetrachloride exposure - solvent used in dry cleaning industry; leads to hepatocyte damage and resultant fatty change Pathological generation of free radicals occurs with: • Ionizing radiation: water is hydrolyzed to hydroxyl free radical (•OH-) • Inflammation: NADPH oxidase generates superoxide free radical ions during oxygen-dependent killing by neutrophils. • Metals (Fe2+ and Cu): generate hydroxyl free radicals (•OH-) via the Fenton reaction. Ex: Hemochromatosis and Wilson Disease -- free radical formation is the UNDERLYING mechanism! • Drugs and Chemicals: Cytochrome P450 in the liver metabolizes drugs (e.g., acetaminophen), generating free radicals in the process. Vitamins A, C, E are antioxidants 3 enzymes that are important for the elimination of free radicals: - Superoxide dismutase (mitochondria) - turns superoxide into hydrogen peroxide - Glutathione peroxidase (mitochondria) - 2GSH + free radical ==> GS-SG + H2O2 - Catalase (peroxisomes): H2O2 => O2 + H2O (like catalase positive bacteria)

++++++++++++++++++++++++ Guts Through The Belly-Button: Omphalocele vs Gastroschisis • Which one is covered by a layer of peritoneum? - (Good MNEM) • Which one has bare / uncovered abdominal contents? - (Okay MNEM) • Both are due to failure of the ___ folds of the anterior wall to close.

• Omphaloceles are covered by peritoneum. - MNEM: Abdominal contents are sealed. • Gastroschisis is NOT covered -- raw intestines visible. - MNEM: Abdominal contents are coming out of the G (G for gastric) - "schisis" = schism = split -- abdominal wall stays split, causing the intestines to protrude. • Both are due to failed closure of the LATERAL folds of the anterior abdominal wall. - MNEM: Picture the guts hanging out to the side (lateral) • Omphaloceles are caused by failure of those lateral folds of the abdomen to migrate to the umbilicus. Thus, umbilicus is open and intestines poke through.

Zenker Diverticulum: • Definition and classic X-ray appearance • Where do they arise? • True or False Diverticulum? • Presentation, including age

• Outpouching of pharyngeal mucosa through an acquired defect (weak spot) in the muscular wall (false diverticulum -- not all 3 layers involved) • Just above the UPPER esophageal sphincter. Where the pharynx and esophagus meet. • False diverticulum b/c it doesn't involve all layers of the esophageal mucosa. • Food gets stuck in the outpuching, causing hallitosis. Pts also have dysphagia, obstruction, aspiration problems. Usually in ELDERLY males.

Pleomorphic Adenoma: • Composed of what 2 types of tissue? • High recurrence rate due to ...

• Pleomorphic, thus 2 tissue types: Stroma (e.g., cartilage) and Epithelial tissue. • High rate due to islands of the tumor -- often not completely resected so it grows back BENIGN

Esophageal Web: • Definition / appearance • Presentation • Plummer-Vinson Syndrome has Esophageal webs + ___ + ___ (CLASSIC triad - High Yield) • High risk of developing ... of the ...

• See IMAGE. Not really webs. Just protrusion of the esophageal mucosa into the opening, blocking food passage. • Presents with dysphagia (hard to swallow) and regurgitation of poorly digested food. • Plummer-Vinson Syndrome: 1) Esophageal Webs 2) Iron Deficiency Anemia (microcytic, hypochromic, high retic) 3) Glossitis / Beefy red tongue. • High risk of developing SqCC of the esophagus.