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Heterophile ab NEGATIVE Mono-like syndromes
*CMV
HHV-6
HIV
Toxoplasmosis
Wernicke's Aphasia
-word salad: well-articulated, nonsensical speech paired with lack of lang comprehension
-aud association cortex: post part of sup temporal gyrus
- supplied by MCA
Congenital Deficiency of Propionyl CoA Carboxylase
-prevents conversion of propionyl CoA to methylmalonyl CoA
-propionyl CoA derived from= val, ile, met, thr, odd # FA, cholesterol side chains
-Propionic Acidemia: poor feeding, vomiting, hypotonia, lethargy, dehydration, anion gap acidosis
Down Synd Comorbidities
Neuro: MR, early onset Alzheimer's
Cardio: complete AV septal defect, VSD, ASD
GI: duodenal atresia, hirschprung disease
Endo: hypothyroid, DM1, obesity
Heme: ALL (> 5 yo) and AML (<5 yo)
Rheumatology: atlantoaxial stability
MCC of Hypoglycemia in EtOH-ics
Thiamine def= suppression of GNG (pyruvate DH) and TCA cyle (alpha-KG DH)
MCC of Hypoglycemia in advanced renal insuff
impaired clearance of insulin
Avoid Nitrates in Hypertrophic Cardiomyopathy bc...
Nitrates decrease preload, which will increase the LV outflow tract... BUT since the ventricle is abnormally shaped, there is an outflow obstruction
Mets through BM
Clonal proliferation of cells can invade/ metastasize*
1. malignant cells to lose their cell-to-cell adhesion molecules (cadherins)
2. cell receptors to attach to laminin (a glycoprotein) in the basement membrane and to release metalloproteinases (e.g., collagenases, stromelysins, gelatinases) to degrade the basement membrane and other enzymes to degrade the interstitial connective tissue- tissue inhibitors of metalloproteinases neutralize these tumor-produced enzymes and limit the degree of invasion
3. cell receptors to attach to bronectin and other proteins in the extracellular matrix (ECM) and to break it down
4. malignant cells to produce cytokines that stimulate locomotion, so that they can move through basement membranes and the intracellular and extracellular matrices
Bicuspid Aortic Valve
Commonly presents in young, asymptomatic patient with soft systolic ejection at right 2nd ICS
-can cause aortic regurg
MCC of Vaginal Candidiasis
1. Abx use= reduces lactobacilli pop
2. High estrogen levels- preg
3. System corticosteroid therapy
4. Uncontrolled DM
5. Immunosuppression, including HIV
Drug causes of SIADH
-Carbamazepine
-Cyclophosphamide
-SSRI
MC Ankle Sprain due to inversion of plantar-flexed foot
-Ant Talofibular Lig dmg
-ecchymosis at the ant-lat aspect of the ankle
Upper Brachial Plexus Injury
- Musculocutaneous and Suprascapular N.
- dystocia mc in neonates; severe trauma mc in adults
- should adduction, elbow extension, and forearm pronation
Patent foramen ovale
-failure of septum primum and septum secundum to fuse after birth
-can lead to paradoxical emboli
Ventricular Septal Defect
-MC occurs in membranous septum
-Acyanotic at birth bc of L to R shunt
Coronary Blood Flow Peak
-at Early Diastole
-coronary perfusion driven by diastolic pressure
-tachycardia will decrease coronary perfusion
Right Dom Heart
majority of people
-PDA comes off RCA
-SA and AV nodes supplied by RCA
Left Dom Heart
-PDA comes off of LCX
- SA and AV node supplied by LCX
Increased Pulse Pressure
hyperthyroidism, aortic regurgitation, aortic stiffening (isolated systolic hypertension in elderly), obstructive sleep apnea ( sympathetic tone), exercise (transient)
Decreased Pulse Pressure
aortic stenosis, cardiogenic shock, cardiac tamponade, advanced heart failure (HF)
Causes of Spontaneous Depol causing Tachyarrhythmias
Hypokalemia, Hypermagnesemia, or prolonged QT interval
= all cause spontaneous depol of ventricles in phase 3 or 4 and it will cause an extra AP in heart
Direct alpha 1 agonist mediated effects
- vasc smooth muscle contraction= increased afterload and venous return= increased DBP + SBP causes reflexive increase in vagal tone= dec HR and slowed AV conduction
- mydriasis
- increased internal urethral sphincter tone and prostate contraction
Direct alpha 2 agonist mediated effects
- CNS med decrease in BP
- decreased intraocular pressure
- decreased lipolysis
- decreased presyn NE release
- increased platelet aggregation
S. epidermidis
- coag neg
-novobiocin sens
- infective endocarditis and infective arthritis in prosthetic pts
Asymptomatic heart defect in turner's synd
-nonstenotic bicuspid aortic valve
-early systolic , high frequency click over right second IC space
Cardiac Changes w/ Normal Aging
- decreased left ventricular chamber size
- shortened base- to- apex dimension
- ventricular septum becomes sigmoid and shape, with basilar portion bulging into LV outflow tract
- atrophy of myocardium causes increased interstitial connective tissue, often with concomitant extracellular amyloid deposition
- lipofucin pigment accumulation within cardiomyocytes
ARDS
Characterized by the development of hypoxemia and bilateral pulmonary infiltrates in the absence of heart failure
-begins with initial injury of pul alveoli (smoke inhal) or pul endothelium (sepsis) which leads to the recruitment of neutrophils- this worsens the situation and leads to intraalveolar accumulation and hyaline membrane formation

-decreased lung compliance, increased work of breathing, worsened V/Q mismatch, and normal PCWP
Renal Artery Stenosis (histo)
medial fibroplasia, absent internal elastic lamina in areas of aneurysmal dilation
Paget's Disease associate Bone Tm
OSTEOSARCOMA! arising from tibia, femur, humerus, and other bones
-pain doesnt resolve with OTC analgesics
DNA Laddering (Gel Electrophoresis)
- DNA fragments in multiples of 180 bp each
- sensitive indicator of APOPTOSIS
- laddering done by specific endonucleases during haryorrhexis, cleaving DNA at interucleosomal linker regions
- this is not seen in cancer cells, since they evade apoptosis
Warburg Effect
malignant cells undergo high rates of glycolysis to produce macromolecules necessary to sustain rapid cellular growth
Risk Factors of Endometritis
-C-section delivery
-chorioamnionitis
-group B strep colonization
-intrauterine instrumentation
-preterm delivery
-prolonged labor
-prolonged ruptured membranes
-retained products of conception

SIGNS AND SX OF POSTPARTUM ENDOMETRITIS
-fever
-leukocytosis
-uterine tenderness
-foul smelling vaginal discharge
Metabolic derangements assoc with DKA
metabolic acidosis, ketonemia, hyperglycemia, hyperkalemia, hyponatremia
-hyperammonemia can be observed due to muscle degradation
Pulmonary Embolism
V/Q Mismatch, causes hypoxemia that increases ventilation and HR via a chemoreceptor reflex
-hypocapnia b/c hypervent, but unable to compensate for hypoxemia
-resp alkylosis= increased ph and decreased PaCO2
Acanthosis Nigracans
-Obesity/ insulin resistance
-Malignancy of GI or Lungs
Congenital Pyloric Stenosis
-thickening of stomach wall, hypertrophy of smooth muscle pyloric stenosis
-palpable olive mass- epigastric region
-nonbilious projectile vomiting at 2-6 weeks of age
-assoc w/ Macrolides
-hypokalemia, hypochloremic, metab alkalosis
Vomiting
powerfully stimulates metabolic alkalosis through direct loss of Hþ, loss of Cl , and volume depletion
Chronic diarrhea
may cause a metabolic alkalosis because of volume contraction
Respiratory compensation for metabolic alkalosis
hypoventilatory capacity limited owing to resulting hypoxemia
Mineralocorticoid excess
think volume expansion, hypertension, hypokalemia, hypernatremia, metabolic alkalosis
Essential tremor
-worsens when maintaining particular postures
-improve/ subside with etoh
-tx: propranolol
-AD inheritance= Familial tremor
Serotonin Synd
confusion, agitation,tremor, tachycardia, htn, clonus, hyperreflexia, hyperthermia, diaphoresis
TX: Cyproheptadine= 1st gen histamine antag, nonspec 5-HT1 and 5-HT2 rec antag
Tensilon Test
-Cholinergic Crisis: muscles stop responding to the bombardment of ACh, leading to flaccid paralysis, respiratory failure, and other signs and symptoms reminiscent of organophosphate poisoning. Other symptoms include increased sweating, salivation, bronchial secretions along with miosis.-- Flaccid paralysis resulting from cholinergic crisis can be distinguished from myasthenia gravis by the use of the drug edrophonium (Tensilon), which worsens the paralysis caused by cholinergic crisis, but strengthens the muscle in the case of myasthenia gravis. (Edrophonium is an cholinesterase inhibitor hence increases the concentration of acetylcholine present).


under-tx'd MG pt presents with exaggerated MG sx, and when infused with edrophonium the sx subside it indicates that the MG treatment (AChE inhib) need to increase in dose
Opioid action on mu rec
-g-protein coupled activation of K+ efflux= hyperpol and pain transmission termination
-inhib adenylyl cyclase
-inhib Ca2+ conductance
-inhib transmitter release
neonatal intravascular hemorrhage
-mc in fragile germinal matrix
-inc freq with decreased age and birth wt
-mc complication would be long term neurodev impairment (alt consciousness, hypotonia, dec spont mvmnt)
-s/sx of bleed: bulging ant frontanelle, hypotension, decerebrate posturing, tonic-clonic seizures, irreg respirations, coma
Acute Rheumatic fever
-endemic in dev countries
-molecular mimicry: anti group a strep ab attack host antigens on cardiac and neuronal tissue approx 2-4 weeks post acute pharyngitis (aka cross reactivity of ab against bacterial and host antigens)
-acute/subacute: migratory arthritis, pancarditis, Sydenham chorea
-Chr: mitral regurg/ stenosis
-tx: PCN
Spironolactone + HF
improve survival of CHF pts with low LV ejection fraction
-block aldosterone's effect on heart and decrease fibrosis and ventricular remodeling
-used with ace-inhib and beta-blockers
Common S/E of Thiazide Diuretics
acute kidney injury, decreased Na+ and K+, hyperuricemia/ acute gout, elevated glu and cholesterol levels
Common S/E of ACE-Inhib
cough, angioedema, inc K+
CCB (diphenhydropine) S/E
periph edema, dizziness/ lightheadedness
Beta Blocker S/E
bronchospasm, bradycardia, fatigue, sexual dysfunction
HTN and at risk for Osteoporosis
THIAZIDES! increased bone mineral density b/c increase in Ca2+ abs in DCT
Methylmalonyl-CoA mutase Def
-AR
-increased urine: methylmalonic acid and propionic acid
-hyperammonemia, ketotic hypoglycemia, and metab acidosis
-newborns present with lethargy, vomiting, and tachypnea
TCA Effect on Cardiac Na+ Channel
BLOCKS cardiac fast Na+ channels= QT and QRS prolongation and arrhythmias
-treated with Sodium Bicarb
MC Complication post Subarachnoid Hemorrhage
SAH sx: thunderclap ha, confusion, fever, nuchal rigidity
MC Compl: VASOSPASM!
-vessels surrounding ruptured aneurysm
-cerebral ischemia and new onset confusion and/or focal neuro deficits (paresthesia, weakness, etc) 4-12 days post SAH
-mech of vasospasm is related to impaired brain autoreg
-not seen on CT, need transcranial color doppler
-Nimodipine prescribed to prevent vasospasm post-SAH
Most Serious Compl of SAH
REBLEED!
-sudden dev of severe confusion, HA, N/V, decreased consciousness, focal neuro deficits
-seen on CT
t(8;14)
Burkitt lymphoma (c-myc activation)
-cmyc is an oncogene
-very aggressive, rapid proliferation of cell growth
t(9;22) aka Philadelphia chromosome
CML (BCR-ABL hybrid), rarely ALL
-constitutive expression of tyrosine kinase
-poor prognosis when expressed in ALL
t(11;14)
Mantle cell lymphoma (cyclin D1 activation)
-cyclin D1 is a cell cycle regulator
-this translocation continuously allows cells to go on in cell cycle without stopping/ apoptosis
t(14;18)
Follicular lymphoma (BCL-2 activation)
[Diffuse Large B-Cell Lymphoma]
-bcl-2 inhibits apoptosis normally
-in this CA, there is constant anti-apoptotic activity
t(15;17)
APL (M3 type of AML)
-translocation of retinoic acid rec (chr 15) onto chr 17, blocks maturation and abnormal pro-myelocytes/ blasts increase which can lead to an increase in DIC
t(12;21)
Acute lymphoblastic leukemia/lymphoma
*better prog
Inc RBC, WBC and Platelets
polycythemia= increase hematocrit
Decreased EPO
-Polycythemia Vera (neg feedback)
-Anemia of Chr Disease
-Chr Kidney Disease
Corticosteroids cause ...
-Neutrophilia, despite causing eosinopenia and lymphopenia
-Corticosteroids activation of neutrophil adhesion molecules, impairing migration out of the vasculature to sites of in ammation
- BUT, sequester eosinophils in lymph nodes and cause apoptosis of lymphocytes
Neutropenia
Sepsis/postinfection, drugs (including chemotherapy), aplastic anemia, SLE, radiation
Lymphopenia
HIV, DiGeorge syndrome, SCID, SLE, corticosteroids, radiation, sepsis, postoperative
Eosinopenia
Cushing syndrome, corticosteroids
MM
- Inc susceptibility to infection
- Primary amyloidosis (AL)
- Punched-out lytic bone lesions on x-ray = activated RANK-L increased osteoclast activity
- M spike on serum protein electrophoresis
- Ig light chains in urine (Bence Jones protein)
- Activated IgG prod by plasma cells by IL-6, may lead to proteasome inhib
- Rouleaux formation (RBCs stacked like poker chips in blood smear)
CO Poisoning
Normal PO2 (dissolved O2)
Decreased %sat of Hb
Decreased total O2 content

= makes Fe2+ into Fe3+(ferric), leading to the formation of methemoglobin which cannot bind to O2- this causes a left shift on the saturation curve- methemoglobin will present with cyanosis

causes dusky discoloration in skin
Pure Red Cell Aplasia (PRCA)
-Inhib of erythroid precursors and progenitors by IgG autoantibodies or cytotoxic T cells
- Marrow failure characterized by hypoplasia of erythroid elements but normal granulopoiesis and thrombopoiesis
- Assoc with thyoma, lymphocytic leukemias, and parvovirus B19 infection
Asthma
Dec FEV1/ FVC
Exp wheeze
Caused by env and genetics
Chr Eosinophil Bronch: IL-5 by TH2 cells
MPB= bronch epith dmg- mc in exercise induced asthma
Cause of LVHF shortness of breath
Impaired diastolic return of Pul v. because high end diastolic pressure causes an increase in hydrostatic pressure and transudate leaks out into the interstitium--> causes affected tissue to swell and increased resistance of movement due to decreased lung compliance
= the neg pressure generated normally from inspiration isnt enough to distend the lungs, causing poor gas exchange and sob
Reduced pulmonary compliance
-LV Heart Failure + Pul Congestion
-Pul Fibrosis
-Insuff Surfactant

decreased compliance= decreased FRC
Surfactant
-cortisol/ thyroxine ↑synthesis
-insulin ↓ synthesis
Pulmonary infarction
-Pulmonary infarction: MC site lower lobes
-Saddle embolus: sudden death
-dyspnea/tachypnea MC symptom/sign
-respiratory alkalosis; hypoxemia; ↑D-dimers
Caplan syndrome
pneumoconiosis + cavitating rheumatoid nodules
Perfusion-limited gas exchange
-diffusion can increase only if blood flow increases
-examples: N2O and O2 under normal conditions
Diffusion-limited gas exchange
-diffusion continues as long as pressure gradient exists across pulmonary membrane
-examples: O2 during vigorous exercise at high altitude and CO
pathophysiologic mechanisms that reduce diffusing capacity
(1) increased thickness of the pulmonary membrane in restrictive diseases (the primary factor in silicosis and idiopathic pulmonary fibrosis)
(2) collapse of alveoli and lung segments (atelectasis), which contributes to a decreased surface area available for gas exchange (e.g., with bed rest after surgery)
(3) poor lung compliance, resulting in insufficient ventilation (e.g., silicosis)
(4) destruction of alveolar units, which also decreases surface area (e.g., emphysema)
Physiologic shunt
-This occurs when blood is appropriately directed to the lungs but is not involved in gas exchange
-EX bronchial arterial circulation= The bronchial arteries supply the bronchi and supporting lung parenchyma but
are not involved in gas exchange at the level of the alveoli
Physiological Shunts in Pathological Cases (Disease states)
-pneumonia or pulmonary edema
-impaired ventilation may result in perfusion of unventilated alveoli
Anatomic Shunt
-Blood flow bypasses lungs
-Increased perfusion of bronchial arteries in chronic inflammatory lung disease
Left-to-Right Shunt
-Bypasses systemic circulation
-May cause pulmonary hypertension and
eventual right-to-left shunt
-Patent ductus arteriosus, ventricular septal defect
Right-to-left Shunt
-Bypasses pulmonary circulation
-Tetralogy of Fallot, truncus arteriosus, transposition of great vessels, atrial septal defect
Compromised airways in Obstructive Airway Diseases
-Residual volume increases because inspiratory volumes are always slightly greater than expiratory volumes, leading to an increase in the AP diameter or the chest
-This explains the "barrel-chested" appearance of patients with emphysema
-Dynamic air trapping during exercise is a major limitation to rigorous activity in patients with chronic obstructive pulmonary disease (COPD)
-Air trapping results in an elevated FRC at which tidal breaths occur--> airways are more patent, which reduces airflow resistance particularly during expiration; this decreases the work of breathing
Restrictive Lung Disease
-do not have difficulty emptying their lungs, FVC typically decreases because they are unable to adequately fill their lungs during inspiration
-inspiration is limited by noncompliance of the lungs, which limits expiratory volumes
-elastic recoil of the lungs is largely preserved (if not increased), the FVC is typically reduced more than is the FEV1, resulting in an FEV1/FVC ratio that is normal or increased
-decreased TLC
Obstructive Lung Capacity
-expiratory volumes are reduced because of airway narrowing and sometimes a loss of elastic recoil in the lungs
-Total expiratory volumes are largely preserved, but the ability to exhale rapidly is substantially reduced
-FEV1 is reduced more than is FVC, and the FEV1/FVC ratio is reduced
-increased TLC
Mechanically Ventilated Patients
-The amount of anatomic dead space increases considerably b/c the volume of space occupied by the respiratory apparatus from the patient's mouth to the ventilator must be considered to be anatomic dead space
-Alveolar ventilation is altered, and care must be taken to ensure adequate oxygenation
Decreased Alv Ventilation
-falls to a level too low to provide sufficient oxygen to the tissue, patients must compensate by increasing the rate of breathing (tachypnea) or by taking larger-volume tidal breaths
-taking larger tidal breaths would be better because it minimizes the effect of dead space on alveolar ventilation
Elevated Alveolar-Arterial Gradient: V/Q Mismatch
-Pulmonary embolism
-Airway obstruction
-Interstitial lung disease
Elevated Alveolar-Arterial Gradient: Shunt
- Intracardiac Shunt (VSD)
- Intrapulmonary Shunt (pulmonary AVM, pneumonia, CHF)
- Atelectasis
Elevated Alveolar-Arterial Gradient: Diffusion defects
-Pulmonary fibrosis
-Emphysema
-Asbestosis
Ureteric Bud
-caudal end of mesonephric duct
-gives rise of ureter, pelvises, calyces, and collecting ducts
-canalized by 10th week
Metanephric Mesenchyme
- interacts with ureteric bud that induces differentiation and formation of glomerulus through the distal convoluted tubules
Renal Artery Stenosis
-MCC: atherosclerosis or fibromuscular hyperplasia. In unilateral renal artery stenosis, hypertension may occur because decreased perfusion of the affected kidney is incorrectly "interpreted" as intravascular volume depletion, which triggers a neurohormonal cascade response (the RAAS and ADH)--> causing fluid retention and vasoconstriction resulting in hypertension
-When both renal arteries are affected (bilateral renal artery stenosis), renal blood flow may become so compromised that the kidneys are unable to perform their normal recycling functions, resulting in the toxic accumulation of metabolic byproducts
Loop Diuretic effect on Tubuloglomerular Feedback
-The juxtaglomerular apparatus is informed of NaCl in the tubular lumen by virtue of its transport into the cells of the macula densa by the same Na+-K+-2Cl- cotransporter that is inhibited by loop diuretics
-One reason for the potency of loop diuretics is their ability to blunt tubuloglomerular feedback and thereby maintain GFR (and urine production) despite increased NaCl traffic past the macula densa
Acute Tubular Necrosis
-MCC: acute renal failure-- which results when hypotension (ischemia, hypoxemia) or tubular toxins damage renal tubular epithelial cells
-Dysfunction of these cells--> sodium and water reabsorption in the proximal tubule is impaired
-Large amounts of NaCl and water are therefore presented to the macula densa-- via tubuloglomerular feedback, this decreases renal blood flow and GFR by stimulating vasoconstriction of the afferent arteriole
-The subsequent decrease in GFR may play a role in limiting potentially life- threatening losses of sodium and water that might otherwise occur in ATN
PCT: Isosmotic reabsorption
reabsorption of fluid along the proximal tubule in which there is no change in tubular osmolality
Glomerulotubular balance
balance among GFR, peritubular oncotic pressure, and proximal tubular reabsorption
Response to volume- depleted state
Decreased RPF --> Increased filtration fraction to maintain GFR --> Increased peritubular oncotic pressure --> Increased proximal tubular reabsorption --> Increased ECF volume
Response to volume- expanded state
Increased RPF --> Decreased filtration fraction to maintain GFR--> Decreased peritubular oncotic pressure --> Decreased proximal tubular reabsorption --> Increased urinary losses--> Decreased ECF volume
Probenecid
-Probenecid and penicillin use organic anion transporters for elimination into the urine
-Probenecid can be used clinically to reduce elimination of penicillin because it competes for the anion transporter, thereby increasing plasma penicillin levels
Diuretics become less effective in individuals with renal failure
-With the exception of spironolactone, an aldosterone receptor antagonist, diuretics must gain access to the tubular lumen to reach their site of action
-Because they are highly protein bound, they are not filtered through the glomerulus-- Instead, they are transported into the tubular lumen through the organic ion transporters located in the basolateral membrane of the proximal tubular epithelial cells
-Renal Failure= This diminished efficacy occurs in part because other organic ions accumulate in renal failure and compete with diuretics for transport into the tubular lumen
-Large doses of diuretics, particularly loop diuretics, are given in renal failure to overcome this competition for tubular secretion
Increased tubular flow rate in LOH
-slow flow rate is required for a countercurrent system to work effectively
-increased flow rate: its ability to function as a countercurrent system and maintain a hyperosmolar interstitium will become compromised
-dilute urine will then be produced in large amounts
***This is one mechanism by which loop diuretics function in promoting diuresis—by increasing the tubular flow rate and compromising the ability of the loop of Henle to function as a countercurrent system
The inner medullary collecting tubules are variably permeable to urea
-permeability Increases in presence of ADH
-ADH Increases urea permeability of inner medullary collecting duct --> urea exits tubular lumen to create more hypertonic interstitium --> Increases [urine]
Acute kidney injury
Often results in hyperkalemia
Regulation of the extracellular potassium pool
***Extremely important, because modest changes in plasma levels can precipitate neuromuscular symptoms and lethal cardiac arrhythmias

-These occur because the resting membrane potentials of nerves and muscle are directly related to the ratio of intracellular and extracellular potassium concentrations
Drugs that cause hyperkalemia
= inability of potassium to be moved intracellularly
-digitalis
-insulin
-abuterol
Patient with HTN and Hypokalemia = increased renin and increased aldosterone
SECONDARY HYPERALDOSTERONISM
-renovasc htn ( renal a. stenosis)
-malignant HTN
-renin secreting tm (JG cell tm)
- diuretic use
Patient with HTN and Hypokalemia = decreased renin and increased aldosterone
PRIMARY HYPERALDOSTERONISM
-Aldosterone prod Tm
-Bilateral adrenal hyperplasia
Patient with HTN and Hypokalemia = decreased renin and decreased aldosterone
-CAH
-Adrenal tumor
-Cushing Synd
-Exogenous mineralocorticoid
MM Symptoms
-fatigue= d/t anemia
-constipation= d/t hypercalcemia
-bone pain, mostly in the back and ribs= d/t osteoclast activating factor prod by myeloma cells
-elevated serum protein= monoclonal protein
-renal failure
-"myeloma kidney"= excess excretion of free light chains (bj proteins), and when the levels exceed the reabs capacity they will precipitate with Tamm Horsfall protein and form casts that cause tubular obstruction and epithelial injury --> tubular dysfxn
-glassy casts stain eosinophillic
Leukocyte adhesion defciency (LAD)
-due to selectin or CD11a/ CD18 deficiency aka and integrin defect
- Delayed separation of the umbilical cord (usually separates and sloughs by the end of the second postnatal week)-- Neutrophil enzymes are important in cord separation; therefore in a histologic section of the surgically removed umbilical cord, no neutrophils would be seen adhering to venular endothelium or be seen in the interstitial tissue
- Additional clinical findings include severe gingivitis, poor wound healing, and peripheral blood neutrophilic leukocytosis (loss of the marginating pool)
- Recurrent bact infections without pus
Lupus related thrombosis
-DVT
-hepatic v. thrombosis
-placental thrombosis (recurrent preg loss)
-stroke

TX: lifelong anticoag
Bone Marrow Stem Cells
CD34
Opioids cause biliary colic
-act on mu rec to constrict sphincter of oddi=
increased pressure of common bile duct and gallbladder
-need to discontinue drug and treat pain with other NSAIDS: ketorolac and diclofenac
P-Glycoprotein
-Also known as multidrug resistance protein 1 (MDR1)--transmembrane ATP-dep efflux pump protein with broad specificity for hydrophobic compounds
-Classically seen in adrenal cell carcinoma but also expressed by other cancer cells (eg, colon, liver)
-Used to pump out toxins, including chemotherapeutic agents (one mechanism of responsiveness or resistance to chemotherapy over time)
Hereditary Orotic Aciduria
defect in UMP Synthase
physical and mental retardation
megaloblastic anemia
elev urinary orotic acid
benefit from uridine supplement
Spontaneous Intracranial Hemorrhage
MCC: AV malformations, ruptured cerebral aneurysms, and cocaine abuse
Congenital Cardiac Anomaly assoc with Ruptured Cerebral Aneurysms...
COARCATION OF THE AORTA! (also assoc with Berry aneurysms)
= ruptures d/t HTN of branches of aortic arch proximal to the coarct--> subarachnoid hemorrhage
Clozapine Treatment Guidelines
- specific for treatment-resistant schizo and schizo assoc with suicidality
- A/E: agranulocytosis, seizures, myocarditis, and metab syndrome
Patent Ductus Arteriosus
-PDA= connection b/w pul a. and aorta that should've obliterated at birth
-continuous machine like murmur= L to R shunt
- large PDA can progress to pul htn and reversal of shunt (R to L shunt)
- can lead to heart failure= SOB, fatiguability
- Eisenmenger's Synd= cyanosis and clubbing that is more pronounced in the lower extremities (in ToF it is whole body cyanosis)
Embolic Phenomena
-Simultaneous dev of stroke, intestinal/ foot ischemia, and renal infarct (wedge shaped) should raise suspicion of an embolic phenomena
-These emboli commonly arise from LA or LV clots (common with A-fib) or valvular veg
Aortic Stenosis
-Increase afterload, decrease stroke volume, pulsus parvus et tardus
-Pre-stenotic dilation and concentric LVH (pressure overload)
-Systolic ejection murmur- best at snd Rt. ICS
-Increased amplitude of PMI- closer to the sternum near the 5th ICS
-Decreased pulse and pulse pressure
-angina/ syncope with exercise- caused by increased O2 demand
-Increased velocity of flow across narrowed aortic valve
-Throughout systole + ejection click (crescendo decrescendo)
-Causes: Age related stenosis, calcification of valve (CAD RF), bicuspid aortic valve, rheumatic fever
-sx: S.A.D= syncope, angina, dyspnea
Aortic Regurg
-Decreased effective SV, *widened pulse pressure
-Increased SV (b/c increased preload) and decreased diastolic pressure --> Water Hammer pulse on exam (hyperdynamic circulation)
-Decreased CO
-LVH and dilation
-Austin Flint murmur= blood hits the anterior leaflet of of aortic valve
-Aortic valve is incompetent= high-pitched diastolic blowing murmur --early diastole; decreases in intensity throughout diastole (decrescendo)
-Turbulent flow back into left ventricle from the high-pressure aorta
-Can cause Pul HTN
-Causes: Syphillis (3) induced aortic aneurysm, CT disorders, endocarditis
-sx: fatigue, syncope, SOB, palpitations
Mitral Stenosis
-Associated with large diastolic pressure difference between left atrium and ventricle
- Increased left atrial pressures --> increased hydrostatic pressures in pulmonary circulation --> pulmonary edema --> RVH and decreased CO
-Sx of pulmonary edema: dyspnea, reduced exercise capacity
-Opening snap + diastolic rumble (diastolic murmur)
-Turbulent flow across stenotic mitral valve during ventricular filling
-LA pushes on esoph
-LA hypertrophy and dilation
Mitral Regurg
-mitral valve does not form good seal--> blood flows into left atrium during early systole
-Precise symptoms of mitral regurgitation depend on temporal course of the mitral regurgitation
-acute onset--> severe symptoms
-chronic onset--> typically asymptomatic or minor symptoms
-MVP: classically gives rise to a midsystolic "click" on auscultation
-Turbulent flow into left atrium during ventricular systole
-Murmur lasts throughout systole
Systolic heart failure
pump failure (impaired contractility, increased afterload)
Diastolic heart failure
impaired ventricular filling during diastole due to stiff ventricle or obstruction to ventricular filling (e.g., mitral stenosis)
Estrogen-containing oral contraceptives
-Inhibiting the LH surge that is responsible for ovulation
-Estrogen-containing contraceptives provide a constant level of estrogen that maintains a continual negative feedback on pituitary gonadotropin secretion, thereby stabilizing FSH and LH secretion
Progesterone-only OCPs
-50% effective in inhibiting ovulation
-work primarily by thickening the cervical mucus and altering the motility and secretions of the fallopian tubes, as well as thinning the endometrium
- All these changes make the uterus a less hospitable environment for implantation of a fertilized embryo
-Inhibits implantation and therefore pregnancy, it does not prevent fertilization
Precocious puberty
-Normal karyotype
-Premature maturation of arcuate nucleus in
hypothalamus
-Treat with GnRH agonists (e.g., leuprolide)
5a-Reductase deficiency
-Normal karyotype
-Insufficient conversion of testosterone to active dihydrotestosterone form
-Female develops internal male genitalia
-Ambiguous external then male external during puberty
Klinefelter syndrome
-47,XXY karyotype
-Meiotic nondisjunction of X chroms
-Male with eunuchoid body, gynecomastia, testicular atrophy, tall, long extremities, female hair distribution, dev delay, infertility, some psychosocial abnorm (lack of insight or judgment)
-Testicular atrophy; fibrosis seminiferous tubules/Sertoli cells; Leydig cells prominent
-Dysgenesis of seminiferous tubules --> decreased inhibin---> increased FSH
-Abnormal Leydig cell function--> decreased testosterone --> increased LH--> increased estrogen
Androgen insensitivity syndrome (male pseudohermaphroditism)
-XY karyotype
-Androgen receptor defect
-Male internal genitalia but incompletely virilized, ambiguous, or female external genitalia
-These individuals do not have male internal genitalia (no epididymis, seminal vesicles, vas deferens, prostate), and most have normal female-looking external genitalia with a blind-ending vaginal pouch
-Increased testosterone, estrogen and LH
-Primary amenorrhea
Female pseudohermaphroditism
-46,XX karyotype
-Gonads are ovaries, but virilization of external genitalia
-Congenital adrenal hyperplasia (21-hydroxylase deficiency)
True hermaphroditism
-46,XX karyotype, most common, followed by 46,XX/46,XY mosaicism
-No sertoli cells or lack of mullerian inhibitory factor
-Presence of both ovarian and testicular tissues
-Ovulation and spermatogenesis may both occur
Turner syndrome
-45,XO karyotype with absent Barr body
-Meiotic nondisjunction
-Streaked ovaries, amenorrhea, short stature, webbed neck/ cystic hygroma (lynch defects), (preductal) aortic coarctation, shield chest, bicuspid aortic valve, horseshoe kidney, cubitus valgus, menopause before menarche
- decreased estrogen leads to increased LH, FSH
Pituitary during pregnancy
-pituitary gland doubles in size during pregnancy because of prolactin synthesis
-prolactin release is inhibited by the high levels of progesterone during pregnancy
Pituitary apoplexy
-hemorrhage into preexisting adenoma → hypopituitarism
-RF: trauma, pregnancy (Sheehan postpartum necrosis, a nontumorous cause), treatment of a prolactinoma with bromocriptine
-headache, mental status dysfunction, visual disturbances
-hormone dysfunction
SCD + Pituitary
Hypopituitarism from HbSS anemia: infarction; vascular occlusion by sickled cells
Lymphocytic hypophysitis
autoimmune destruction during/after pregnancy
Empty sella syndrome
-radiologic studies show an empty sella turcica
-subarachnoid space extends into sella
-↑CSF pressure compresses gland-- increase in pressure on the pituitary gland causes it to flatten out and undergo
atrophy
-obese with hypertension
Estrogen Effects on TBG and Thyroid Hormones
Changes in TBG: alter total serum T4; no effect on FT4 and TSH

-↑TBG → ↑total serum T4 but not FT4
-↑Estrogen: pregnancy, OCPs, hormone replacement
-↓TBG: ↓total serum T4 but not FT4
-↓TBG: anabolic steroids, nephrotic syndrome
↓Serum TSH
thyrotoxicosis, hypopituitarism, hypothalamic dysfunction
123-I (radioactive) uptake
= used to evaluate synthetic activity of thyroid gland

-↑123-I uptake: ↑ synthesis of thyroid hormone= Graves disease
-↓123-I uptake: thyroiditis, patient taking excess thyroid hormone
-Cold nodule: ↓123-I uptake
-Hot nodule: ↑123-I uptake
Acute thyroiditis
-thyrotoxicosis
-bacterial infection
-↓123-I uptake
-fever
-tender gland with painful cervical adenopathy
-initial thyrotoxicosis from gland destruction-- increased serum T4, decreased serum TSH
-permanent hypothyroidism uncommon
Subacute granulomatous thyroiditis
- MCC painful thyroid
-virus induced-- preceded by URI
-no adenopathy
-granulomatous inflammation with multi-nucleated giant cells
- initial thyrotoxicosis from gland destruction-- increased serum T4, decreased serum TSH
-permanent hypothyroidism is uncommon
-decreased 123-I uptake
-self-limited; does not require treatment
Hashimoto thyroiditis
-autoimmune thyroiditis; hypothyroidism common= human leukocyte antigen (HLA)-Dr3 and HLA-Dr5 associations
-type IV (mainly) and type II hypersensitivity
-helper T cells release cytokines attracting macrophages that damage tissue= (type IV HSR)
-antimicrosomal and antithyroglobulin antibodies destroy parenchyma (type II HSR)
-histo: lymphocytic infiltrate with prominent germinal follicles
-risk factor for primary B-cell malignant lymphoma of the thyroid
Riedel thyroiditis
-Fibrous tissue replacement of gland and surrounding tissue
-Can obstruct the trachea
-Associated with other sclerosing conditions (ex: sclerosing mediastinitis)
-tx: corticosteroids
Subacute painless lymphocytic thyroiditis
-develops postpartum; progression to hypothyroidism
-abrupt onset of thyrotoxicosis due to gland destruction
-slightly enlarged and painless gland
-progresses to primary hypothyroidism
-tx: levothyroxine in the hypothyroid stage
Toxic multinodular goiter
-one/more nodules in multinodular goiter become TSH-independent
-no exophthalmos/pretibial myxedema
Thyrotoxicosis
-weight loss
-heat intolerance
-anxiety
-diarrhea
-oligomenorrhea and lid stare
-atrial fibrillation, sinus tachycardia, systolic HTN, high output failure
- brisk reflexes, osteoporosis
-↑glucose, calcium, lymphocytes; ↓cholesterol
Graves hyperthyroidism
↑serum T4/FT4, ↑123I uptake, ↓serum TSH
tx: β-blockers, thionamides
Thyroid storm
causes:
-inadequately treated patients with Graves disease undergo surgery
-infection, trauma
-iodine, pregnancy
sx:tachyarrhythmias, hyperpyrexia, coma, shock (volume depletion from vomiting)
Tx:
(1) Inhibit hormone synthesis: Propylthiouracil or Iodide
(2) Sympathetic blockade with β-blockers
(3) Hydrocortisone
(4) Cooling blanket
Solitary Thyroid Nodules
-Solitary nodule in a woman: majority are benign--15% malignant
-Solitary nodule in a man or child: more likely to be malignant

First step in management solitary thyroid nodule: FNA
Follicular adenoma
- MC benign thyroid tumor
-surrounded by complete capsule
-solitary "cold" nodule
Papillary adenocarcinoma
-mc endocrine cancer
-radiation exposure***
-multifocal, papillary fronds intermixed with follicles, psammoma bodies, Orphan Annie nuclei, lymph invasion
-mets: cervical nodes, lung
Follicular carcinoma
-mc thyroid cancer presenting as solitary cold nodule
-encapsulated or invasive
-hematogenous rather than lymphatic spread
-mets: lung, bone
Medullary carcinoma
-sporadic > familial-- familial type has a better prognosis than the sporadic type
-autosomal dominant MEN IIa/IIb
-derives from C cells; calcitonin tumor marker
-calcitonin converted into amyloid
Primary B-cell lymphoma
-most often derives from Hashimoto thyroiditis
Resp Alkylosis + Ca2+ Homeostasis
-Respiratory alkalosis:increases negative charges on albumin, extra negative charges bind some of the ionized calcium, normal total serum calcium
-↓ionized calcium, ↑PTH
-tetany: due to a decreased ionized calcium level= thumb adducts into palm; facial twitching after tapping facial nerve
Hypoparathyroidism
-MCC is autoimmune hypoparathyroidism
-other causes: thyroid surgery, digeroge synd, hypomagnesemia: mc pathologic cause of hypocalcemia in hospital
-↓serum calcium, PTH; ↑serum phosphorus
-tetany, calcification of basal ganglia, cataracts, Candida infections
Hypomagnesemia
diarrhea, aminoglycosides, diuretics, alcohol
Primary hyperparathyroidism
-MC nonmalignant cause of hypercalcemia
-MEN I, IIa association
-MCC of 1° HPTH: benign adenoma
-primary hyperplasia: all four glands involved-- chief cell hyperplasia
-renal stones, nephrocalcinosis; metastatic calcification, PUD, acute pancreatitis, osteitis fibrosa cystica; subperiosteal bone resorption; osteoporosis; pseudogout, diastolic HTN, band keratopathy, psychosis, confusion, anxiety, coma
-↑serum calcium/PTH; ↓serum phosphorus/bicarbonate; chloride/phosphorus ratio >33
Addison disease
Chronic adrenal insufficiency
-diffuse hyperpigmentation; hypotension, weakness
-↓serum sodium, cortisol, bicarbonate
-↑serum potassium, ACTH
-hypoglycemia, eosinophilia, lymphocytosis, neutropenia
1° Aldosteronism
-adrenal adenoma (Conn syndrome) or idiopathic adrenal hyperplasia
-hypertension, hypernatremia, hypokalemia, metabolic alkalosis *** no edema bc of the Aldosterone escape mech = increased RBF, GFR, and ANP
- increased aldosterone, decreased renin
2° Aldosteronism
-renovascular hypertension, juxtaglomerular cell tumor
-compensates for ↓cardiac output; activates RAA system
-increased aldosterone, increased renin
Neuroblastoma
-malignant tumor of postganglionic sympathetic neurons-- adrenal medulla tm
-neural crest cells
-childhood tumor and cause of hypertension
-N-MYC oncogene (nuclear transcriber) amplification
-increased HVA and VMA (catecholamine metabolites) in urine
-Homer-Wright rosettes B characteristic of neuroblastoma and medulloblastoma
-bombesin and NSE ⊕
-Opsoclonus-myoclonus syndrome: paraneoplastic syndrome; myoclonic jerk; chaotic eye movements
Fasting Hypoglycemia when EtOH excess
↓glycogen stores
↓gluconeogenesis (pyruvate converted to lactate)
Whipple triad
(1) Symptoms occur: adrenergic and neurological sx
(2) Hypoglycemia
(3) Symptoms are relieved by glucose
Cushing disease
-Pituitary Cushing syndrome
-Due to a pituitary adenoma
-↑ACTH, ↑cortisol
-bilat adrenal hyperplasia
Adrenal Cushing syndrome
-Primary adrenal adenoma, hyperplasia, or carcinomas
-↓ACTH, ↑cortisol
-atrophy of the uninvolved adrenal gland
-can present as primary aldosteronism (Conn synd)
Ectopic Cushing syndrome
-paraneoplastic: small cell carcinoma of lung; less commonly thymus, thyroid
-↑↑ACTH, ↑cortisol
-bilat adrenal hyperplasia
Exogenous Corticosteriods
-Cushing syndrome: MCC
-Decreased ACTH
-bilateral adrenal atrophy
Pheochromocytoma
-majority benign, unilateral, arise in adrenal medulla
-neurofibromatosis; MEN IIa/IIb (RET); von Hippel- Lindau disease; Sturge-Webber Synd
-palpitations, paroxysmal hypertension, anxiety, drenching sweats, headache, orthostatic hypotension, chest pain, ileus
-Tm: brown, hemorrhagic, and o en necrotic
-Dx: plasma free metanephrines best screen
-Urine tests: 24-hour collection for metanephrine (best test), VMA
-lab: hyperglycemia, neutrophilic leukocytosis
Nelson Synd
enlarged existing ACTH-sec pituitary adenoma after bilat adrenalectomy for refractory Cushing's D (to remove the cortisol feedback)
-sx: hyperpig, HA, bitemporal hemianopia
Jod-Basedow phenomenon
-Thyrotoxicosis if a patient with iodine deficiency and partially autonomous thyroid tissue (eg, autonomous nodule) is made iodine replete
-Opposite of Wolff-Chaikoff effect
Pseudohypoparathyroidism type 1A (Albright hereditary osteodystrophy)
-Unresponsiveness of kidney to PTH hypocalcemia despite PTH levels
-Characterized by shortened 4th/5th digits, short stature
-Autosomal dominant
-Due to defective Gs protein α-subunit causing end-organ resistance to PTH
-Defect must be inherited from mother due to imprinting
Pseudopseudohypoparathyroidism
-physical exam features of Albright hereditary osteodystrophy but without end-organ PTH resistance
-Occurs when defective Gs protein α-subunit is inherited from father
MEN 1
-Pituitary tumors (prolactin or GH) Pancreatic endocrine tumors—Zollinger-Ellison syndrome, insulinomas, VIPomas,glucagonomas (rare)
-Parathyroid adenomas
-Associated with mutation of MEN1 (menin, a tumor suppressor, chromosome 11)
MEN 2a
-Parathyroid hyperplasia
-Medullary thyroid carcinoma—neoplasm of
parafollicular or C cells; secretes calcitonin;
prophylactic thyroidectomy required
-Pheochromocytoma (secretes catecholamines)
-Associated with mutation in RET (codes for
receptor tyrosine kinase) in cells of neural crest origin
MEN 2b
-Medullary thyroid carcinoma
-Pheochromocytoma
-Mucosal neuromas (oral/intestinal ganglioneuromatosis)
-Associated with marfanoid habitus; mutation in
RET gene
Mullerian Duct Abnormalities
-anatomical defects that may present as primary amenorrhea in females with fully developed secondary sexual characteristics (indicator of fxn'l ovaries)
-agenesis because of hypoplastic or absent mullerian duct system
Primary hypogonadism due to Leydig cell dysfunction'
[males]
-alcohol, renal failure, orchitis, radiation
-↓testosterone, sperm count; ↑LH; normal FSH; hypergonadotropic hypogonadism
Primary hypogonadism due to Leydig cell + seminiferous tubule dysfunction [males]
↓testosterone, sperm count; ↑LH; ↑FSH
Secondary hypogonadism [males]
-constitutional delay, Kallmann syndrome, hypopituitarism, prolactinoma; hypogonadotropic hypogonadism
-lab findings: ↓FSH, LH, testosterone, sperm count
Ovulation
-estrogen surge (increase GnRH rec on ant pit) → LH surge → ovulation (rupture of follicle)
-increased temp= progesterone induced
-between days 14 and 16
Causes of pelvic pain= E.C.T.O.P.I.C.
Ectopic (mcc), Endometriosis
Cyst rupture (corpus leutium cyst rupture)
Torsion of ovary (compromise ovarian bl flow) or cyst
Ovulation (mittelschmerz)
PID, salpingitis, tubo-ovarian abscess
Incomplete abortion
Cystitis/pyelonephritis
Increased temperature in Sertoli cells...
decrease sperm production and inhibin when temperature increases

*seen in cryptochidism and varicocele
Breast Milk
-milk letdown is stim by oxytocin
-ideal infant nutrition when <6mo, exclusive breastfed infants require vit D supplementation
-contains: IgA, macrophages, lymphocytes
-reduces infant infections and is associated with the decreased risk of child dev asthma, allergies, DM, and obesity
-breastfeeding decreases maternal risk of breast and ovarian cancer, and facilitates mother-child bonding
Physiol Adaptations during Pregnancy
-increased cardiac output= increased preload and decreased afterload
-increased heart rate= increased placental and adrenal perfusion
-anemia= increased plasma + increase RBCs--> increased viscosity
-hypercoag= decreased blood loss at delivery
-hypervent= eliminate fetal CO2
Menopause
-decreased estrogen prod d/t age linked decline in the number of ovarian follicles (exhaustion of follicles)-- avg onset is 51 yo and earlier in smokers (<35 yo: premature ovarian failure)
-increased FSH is diagnostic for menopause (d/t loss of inhibin/ neg feedback by estrogen)
-hormonal changes: decreased estrogen, increased FSH, increased LH (no surge), increased GnRH
5alpha-reductase def
-SRD5A deficiency, AR
-Sex limited to genetic males (46,XY)
-Inability to convert testosterone to DHT
-Ambiguous genitalia until puberty, when increased testosterone causes masculinization/ increased growth of external genitalia
-Testosterone/estrogen levels are normal; LH is normal or increased
-Internal genitalia are normal
Placental aromatase defciency
-Inability to synthesize estrogens from androgens
-Masculinization of female (46,XX) infants (ambiguous genitalia), increased serum testosterone and androstenedione
-Can present with maternal virilization during pregnancy (fetal androgens cross the placenta)
-males are normal phenotypically
Kallmann syndrome
-AD, maldevelopment of the olfactory bulbs and GnRH-producing cells in the hypothalamus
-↓GnRH --> ↓FSH, LH, testosterone, sperm count
- Delayed puberty, anosmia
-Low sprem count/ infertility in males/ amenorrhea in females
-Can be assoc with midline defects= cleft lip/ palate
Cryptorchidism
- incomplete or improper descent of testis into scrotal sac= seminiferous tubule dmg
-normal testosterone and when unilateral but decreased levels when bilateral
-increased FSH and, low sperm count and inhibin
-risk for seminoma + infertility of cryptorchid testis and normally descended testis
Testis descent
- transabdominal phase: descend to lower abd/ pelvic brim= Müllerian inhibitory substance (MIS) is responsible for this phase
- inguinoscrotal phase: androgen- and hCG-dependent
Chorioamnionitis
-infection in fetal membranes
-danger of neonatal sepsis/ meningitis
Placenta previa
-implantation over cervical os-- placenta attaches to lower uterine segment
-previous C-section risk factor
-painless vaginal bleeding
-dx by US; deliver by C-section
Abruptio placentae
-premature seperation (partial or complete) of placenta from uterine wall before delivery of infant
-retroplacental clot, MCC of late pregnancy bleeding
-hypertension is greatest risk factor
-triad: painful vaginal bleeding, tetanic contractions, fetal compromise
- no pelvic exam; dx with US
-possible DIC, maternal shock, fetal distress
-life threatening for mom and baby
Placenta increta/ percreta
implantation into muscle; danger of hemorrhage at delivery
-Placenta increta—placenta penetrates into myometrium
-Placenta percreta—placenta penetrates ("perforates") through myometrium and into uterine serosa (invades entire uterine wall); can result in placental attachment to rectum or bladder

-Defective decidual layer= abnorm attachment and separation after delivery
-No separation of placenta after delivery postpartum bleeding (can cause Sheehan syndrome)
Placenta accreta
-placenta attaches to myometrium without penetrating it
-most common type
-Defective decidual layer= abnorm attachment and separation after delivery
-No separation of placenta after delivery postpartum bleeding (can cause Sheehan syndrome)
Enlarged placenta
Rh Hemolytic Disease of Newborn, congenital syphilis, DM
Polycystic ovary syndrome (PCOS)
-↑incidence insulin-resistance, obesity, acanthosis nigricans
-LH/FSH ratio >3
-↑serum free tesosterone/ androstenedion
- ↓serum SHBG; normal to ↓serum FSH
-↑secretion LH → follicular hyperthecosis (hyperplasia ovarian thecal cells) → ↑production testosterone, androstenedione → hyperandrogenicity (e.g., hirsutism)
-chronic anovulation (less aromatization of androgens to estrogen)
-follicular arrest, subcortical cysts
-↑conversion androstenedione to estrone → ↑endometrial hyperplasia/cancer, breast cancer risk
- oligomenorrhea, hirsutism, obesity, infertility
- first line tx: OCPs= Induce regular menses, inhibits ovarian androgen production, increases sex
hormone-binding globulin (SHBG) production
Homocystinuria
-downward & inward lens dislocation (down & in)
-AR, heart rarely affected
-mental retardation
-osteoporosis, recurrent thromboembolism
-characteristic laboratory features - plasma methionine and homocystine levels are elevated, homocystine is excreted in the urine, plasma cystine levels are reduced, positive urine cyanide-nitroprusside test
-response to treatment with pyridoxine
Marfan's
-upward & outward lens dislocation (up &out)
-AD, aortic incompetence or MVP may occur
-normal intellectual dev
-flat feet, herniae, scoliosis; there is a 50% reduction in life expectancy
Ischemic area of Brain
ACA/MCA/PCA boundary areas (watershed areas*)
-Neurons most vulnerable to hypoxic-ischemic insults include Purkinje cells of the cerebellum and pyramidal cells of the hippocampus and neocortex
ischemic are of Heart
Subendocardium (LV)
ischemic area of Kidney
Straight segment of proximal tubule (medulla) + Thick ascending limb (medulla)
ischemic area of Liver
Area around central vein (zone III)
ischemia area of Colon
Splenic flexure (watershed areas), rectum (watershed areas)
Tuberous Sclerosis
-tuberin and harmartin mutations
- facial angiofibroma
- seizures
- intellectual disability
- heart defects= cardiac rhabdoyomas in ventricular walls and AV valves, cutaneous angiofibromas (adenoma sebaceum)


assoc neoplasms:
giant cell astrocytoma -- CNS hamartoma
renal angiomyolipoma-- renal cysts
cardiac rhabdomyoma
Failure of endocardial cushion fusion
-ostium primum ASD + VSD + single AV valve = sig L to R shunting and AV valve regurg leads to excessive pulmonary bl flow and sx of heart failure (tachypnea, poor feeding, etc) in a neonate
-hear an AV valve regurg on auscultation (holosystolic, best at the apex) and increased pulmonary VR (mid-systolic rumble)
Chronic Alcoholism --> Cerebellar Vermis effects
- atrophy to the ant lobes and cerebellar vermis
- resulting in gait ataxia, truncal instability, intention tremor, and rhythmic "Parkinsonism" tremor of the fingers and hands
Electrolyte Changes in Ischemia
-increases extracell K+ conc bc of non-fxn'l Na+/K+/ATPase due to lack of ATP which causes K+ to leak out of cell
-may reduce extracell Na+, Ca2+, and Bicarb concentrations
-cytoplasmic accumulation of Ca2+ ***HALLMARK OF ISCHEMIC INJURY
Lactose Intolerence
down regulation of lactase production of small enterocytes
Dopamine beta-hydroxylase deficiency
-impaired sympathetic adrenergic activity with normal PSNS and sweating
-infant sx: may dev hypotension, ptosis, and hypothermia
-adult sx: postural hypotension, exercise intolerance, nasal congestion, and ejaculatory difficulties
-impaired synth of epi and NE
Zero Order Drugs
EtOH
Salicylates
Phenytoin
Lithium
Malignant Otitis Externa
-common in elderly diabetics
-mcc: pseudomonas aeruginosa, non-lactose fermenting, oxisdase positive, G- rod
-severe ear pain and drainage
-granulation tissue seen in canal but tympanic membrane is intact
-can progress to osteomyelitis of skull and causes CN dmg
ST Elevation in leads II, II, aVF
RCA transmural ischemia of inf wall of LV
(possible sinus node dysfxn=bradycardia and hypotension)
ST Elevations in leads V1-V4
Prox LAD occlusion= anteroseptal transmural ischemia
ST Elevations in leads V1 and V2
transmural ischemia of septum
infranodal (morbitz type II) 2nd degree or 3rd degree heart block is possible result as well
ST Elevations in V5, V6, I, and aVL
transmural ischemia of interventricular septum and LV
Germline mosaicism
-involved in oocytes or spermatocytes
-genetic mutation when not present in parents but only in offspring
-prob of passing it on to further offpspring depends on the ratio of wt to mut alleles in mosaic parent

(diff than somatic mutations which can't be passed on)
Hand- Foot-Genital Syndrome
HOX13 mutation
- distal limb defects, hypoplastic first digits, and GU malform
Meigs Syndrome
ovarian fibroma, ascites, and hydrothorax
*** Fibroma= benign ovarian neoplasm
Heart Morphology of ASD
shunting of blood from LA to RA causes volume overload of RV --> RA enlarged + eccentric (dilated) RVH
Concentric LVH
= pressure overload

-chr htn
-aortic stenosis
Eccentric LVH
=volume overload

-aortic or mitral regurg
-MI
-dilated cardiomyopathy