Leuprolide
GnRH Agonist (Pulsatile Use) GnRH Antagonist (Continuous Use) Upregulates FSH And LH Downregulates FSH And LH Infertility Prostate Cancer Precocious Puberty Uterine Fibroids Endometriosis Anti-androgenic Effects Pyruvate dehydrogenase complex
Mitochondrial enzyme complex linking glycolysis and TCA cycle Differentially regulated in fed/fasting states (active in fed state) Reaction: pyruvate + NAD + CoA to acetylCoA + CO2 + NADH Complex is similar to the α-ketoglutarate dehydrogenase complex (same cofactors, similar substrate and action), which converts α-ketoglutarate to succinyl-CoA (TCA cycle) Arsenic inhibits lipoic acid. Findings: vomiting, rice-water stools, garlic breath Thiamine pyrophosphate (B1 ) Lipoic acid Lipoamide carries acyl groups CoA (B5, pantothenic acid) FAD (B2, riboflavin) NAD (B3, niacin) High NAD+/NADH ratio, ADP, Ca2+ Lenticulostriate Artery (Turned to Lacunar stroke I believe, double check)
Affecred areas: Striatum, internal capsule Contralateral paralysis and/or sensory loss—face and body. Absence of cortical signs (eg, neglect, aphasia, visual field loss). Common location of lacunar infarcts, 2° to unmanaged hypertension and diabetes Hypertension causes lipohyalinosis (hyaline deposition in arteries followed by foamy macrophages) Microarethomas (atherosclerotic accumulation of foamy macrophages) Both lipohyalinosis and microarethomas causes infarction leading to fluid filled cavities May affect the subthalamic nucleus and cause hemibalism If internal capsule involved --> pure motor stroke If thalamus involved --> pure sensory stroke Acute hemorrhage appears hyperdense on noncontrast head CT scan Can cause Dysarthria-clumsy hand Can affect the corona radiata, Pons, basal ganglia Herniation Syndromes
Can compress anterior cerebral artery Caudal displacement of brain stem causes rupture of paramedian basilar artery branches casuing Duret hemorrhages; Usually fatal Hemorrhages occur in the pons and midbrain Uncus = medial temporal lobe. Compresses ipsilateral CN III (blown pupil, “down-andout” gaze), ipsilateral PCA (contralateral homonymous hemianopia with macular sparing) Ipsilateral hemiparesis (due to contralateral corticospinal tract damage) Contralateral crus cerebri at the Kernohan notch (ipsilateral paresis; a “false localization sign" Displacement of the temporal lobe uncus under the tentorium cerebeli Change In LOC (Altered Mental Status) Coma and death result when these herniations compress the brain stem Cardiopulmonary arrest Psychiatric Treatments
Specific phobia - systematic desensitization Postpartum depression - CBT and SSRIs are first line Adjustment disorder - CBT, SSRIs Postpartum psychosis - hospitalization and initiation of atypical antipsychotic; if insufficient, ECT may be used U: antidepressants and mood stabilizer; don't leave alone with baby! Panic disorder - CBT, SSRIs, and venlafaxine are first line. Benzodiazepines occasionally used in acute setting #1 treatment is an SSRI (better than CBT but combination is best) Social anxiety disorder - CBT, SSRIs, venlafaxine. For only occasional anxiety-inducing situations, benzodiazepine or β-blocker Agoraphobia - CBT, SSRIs, MAO inhibitors Generalized anxiety disorder - CBT, SSRIs, SNRIs are first line. Buspirone, TCAs, benzodiazepines are second line Starting doses should be low to minimize initial activating side effects (for SSRI/SNRI) #1 treatment is CBT (better than SSRIs but combo is best) Obsessive-compulsive disorder - CBT, SSRIs, and clomipramine are first line #1 treatment is CBT (better than SSRIs but combo is best) Body dysmorphic disorder and acute stress disorder - CBT, SSRI Post-traumatic stress disorder - CBT (trauma focused), SSRIs, and venlafaxine are first line; prazosin for PTSD nightmares Edit PTSD Bipolar disorder - Lithium, valproic acid, atypical antipsychotics Aliskiren
Direct renin inhibitor Blocks conversion of angiotensinogen to angiotensin I Hypertension Hyperkalemia Decreased GFR Hypotension Relatively contraindicated in patients already taking ACE inhibitors or ARBs Hydronephrosis
Distention/dilation of renal pelvis and calyces (Pictured) Usually caused by urinary tract obstruction (eg, renal stones, BPH, cervical cancer, injury to ureter ie surgery for histerectomy) U. Ureter damage during pelvic surgery Other causes include retroperitoneal fibrosis, vesicoureteral reflux Dilation occurs proximal to site of pathology Serum creatinine becomes elevated only if obstruction is bilateral or if patient has only one kidney Leads to compression and possible pressure atrophy of renal cortex and medulla Associated with increasted EPO, horseshoe kidney, In neonate the ureteropelvic junction is a site of narrowing/kinking of the ureter that can cause hydronephrosis Presents with palpable abdominal mass which is due to an enlarged kidney S haematobium U. Can lead to hypertension and sepsis; symptoms: pain, lower extremity edema, palpable kidneys or bladder Squamous Cell Carcinoma of the Bladder and Adenocarcinoma
Chronic irritation of urinary bladder causes squamous metaplasia leading to dysplasia and squamous cell carcinoma Risk factors include Schistosoma haematobium infection (Middle East), chronic cystitis (older women), smoking, chronic nephrolithiasis Presents with painless hematuria Malignant gland proliferation usually within the bladder Can arise from urachal remnant (at the dome of the bladder), cystitis glandularis or exstrophy of the bladder Urinary Tract Infection (Acute Bacterial Cystitis)
Inflammation of urinary bladder Presents as suprapubic pain/pressure, dysuria, urinary frequency, urgency. Systemic signs (eg, high fever, chills) are usually absent Risk factors include female gender (short urethra), sexual intercourse (“honeymoon cystitis”), indwelling catheter, diabetes mellitus, impaired bladder emptying Benign prostatic hyperplasia E coli (most common) Staphylococcus saprophyticus—seen in sexually active young women (E coli is still more common in this group), second most common Klebsiella (third most common) Proteus mirabilis (urine has ammonia scent) Enterococcus faecalis Pseudomonas Citrobacter (gram negative rod, slow lactose fermenter) Lab findings: ⊕ leukocyte esterase. ⊕ nitrites (indicate gram ⊝ organisms, especially E coli). Sterile pyuria and ⊝ urine cultures suggest urethritis by Neisseria gonorrhoeae or Chlamydia trachomatis Gonorrhea and chlamydia can present with urethritis Urinalysis - cloudy urine with > 10 WBCs/High power field (HPF) alt naming pyuria of urine Culture - Greater than 100,000 colony forming units (gold standard) Leukocyte esterase = significant pyuria, nitrites = presence of Enterobacteriaceae (converts urinary nitrates to nitrites) Acute Pyelonephritis
Neutrophils infiltrate renal interstitium (Pictured, A) Affects cortex with relative sparing of glomeruli/vessels Presents with fevers, flank pain, nausea/vomiting, chills Causes include ascending UTI (E coli is most common), vesicoureteral reflux, hematogenous spread to kidney Other risk factors include indwelling urinary catheter, urinary tract obstruction, diabetes mellitus, pregnancy Kidney stones BPH (Benign Prostatic Hyperplasia) Enterococcus faecalis and Klebsiella Presents with WBCs in urine +/− WBC casts (WBCs precipitate with Tamm-Horsfall protein); leukocytosis CT would show striated parenchymal enhancement (Pictured, B) Complications include chronic pyelonephritis, renal papillary necrosis, perinephric abscess, urosepsis Treatment: antibiotics S haematobium Dysuria, frequency, urgency, bacturia, costovertebral tenderness Can be sterile pyuria in the case of Chlamydia or ureaplasma Perinephric fat stranding Most common pathogen is Escherichia coli (80%), but Proteus mirabilis , Klebsiella pneumoniae , and Staphylococcus saprophyticus as well Urine culture is required for definitive identification Progression to renal corticomedullary abscess , perinephric abscess , emphysematous pyelonephr itis, or papillary necrosis Patients can develop sepsis with multiorgan failure, shock ,and renal failure Risk factors: diabetes, kidney stones, immunosuppression, or other anatomic abnormalities of the urinary tract These patients usually require imaging to evaluate for these complications, urological evaluat ion, and prompt therapy (medical/surgical) Imaging is typically reserved for patients with persistent clinical symptoms despite 48-72 hours of therapy History of nephrolithias is, or unusual urinary findings (eg, gross hematuria, suspicion for urinary obstruction). Emphysematious (gas producing) pyelonephritis is much more common in diabetics and can be slow onset or abrupt (same symptoms as pyelo +/- abd pain) Chronic Pyelonephritis
The result of recurrent episodes of acute pyelonephritis Typically requires predisposition to infection such as vesicoureteral reflux or chronically obstructing kidney stones, BPH or cervical carcinoma Coarse, asymmetric corticomedullary scarring, blunted calyces Tubules can contain eosinophilic casts resembling thyroid tissue (thyroidization of kidney) (Pictured) Vesicoureteral reflux causes upper and lower pole scarring Waxy casts may be seen in urine (Only according to Pathoma, not even google) Interstitial fibrosis and atrophy of the tubules U. has the appearance of dilated calyces Rare Characterized by widespread kidney damage due to granulomatous tissue containing foamy macrophages Grossly orange nodules that can mimic tumor nodules Renal Osteodystrophy
Hypocalcemia, hyperphosphatemia, and failure of vitamin D hydroxylation associated with chronic renal disease 2° hyperparathyroidism Hyperphosphatemia independently decreases serum Ca2+ by causing tissue calcifications Decreased 1,25-(OH)2 D3 causing decreased intestinal Ca2+ absorption 1-alpha hydroxylation usually occurs in the proximal convoluted tubule Causes subperiosteal thinning of bones Can cause osteopenia, osteomalacia or undergo a similar process to primary hyperparathyroidism (osteitis fibrosa cystica) Acute Kidney Injury (Acute Renal Failure)
Acute kidney injury is defined as an abrupt decline in renal function as measured by increased creatinine and BUN; oliguria is common Decreased RBF (eg, hypotension or HF) decreases GFR Na+/H2O and BUN retained by kidney in an attempt to conserve volume Increased BUN/creatinine ratio (BUN is reabsorbed, creatinine is not) and decreased FENa Acute tubular necrosis or ischemia/toxin cause; less common acute glomerulonephritis (eg, RPGN, HUS) or acute interstitial nephritis In ATN, patchy necrosis causing debris obstructing tubule and fluid backflow across necrotic tubule decreasing GFR Urine has epithelial/brown granular casts BUN reabsorption is impaired decreasing BUN/creatinine ratio Aminoglycosides, lead, myoglobinuria (muscle crush injury), ethylene glycol (oxalate crystals in urine), radiocontrast dye, urate (tumor lysis syndrome) Hyperkalemia and metabolic acidosis Persistent oliguria for 2-3 weeks due to tubular cells being stable cells that take time to reenter the cell cycle Due to outflow obstruction (stones, BPH, neoplasia, congenital anomalies) Develops only with bilateral obstruction Consequences of Renal Failure
Inability to make urine and excrete nitrogenous wastes Can be caused by acute renal failure or chronic (eg, hypertension, diabetes mellitus, congenital anomalies, glomerular disease) Treatment: Dialysis (can cause shrunken cystic kidneys with increased renal cell carcinoma risk) Metabolic Acidosis Dyslipidemia (especially increased triglycerides) Hyperkalemia Uremia - clinical syndrome marked by increase in BUN Nausea, anorexia, pericarditis, asterixis, encephalopathy, platelet dysfunction Increased bleeding time (urea impairs aggregation), normal platelet count, PT and PTT Urea crystals deposited in skin Na+/H2O retention (HF, pulmonary edema, hypertension) Growth retardation and developmental delay Erythropoietin failure (anemia) which is usually produced by renal peritubular interstitial cells Renal osteodystrophy (due to secondary hyperparathyroidism), osteomalacia, osteoporsis, bone pain, fractures Can cause osteitis fibrosa cystica from secondary hyperparathyroidism Hypocalcemia and hyperphosphatemia - decrease 1-alpha-hydroxylation of vitamin D by proximal renal tubule cells Increased prolactin due to decreased prolactin excretion Myoclonus Osteomalacia Elevated Anion gap metabolic acidosis Uworld Step 2 says dialysis does not increase cancer risk Anemia: keep Hgb > 10 EPO, Iron Secondary Hyperparathyroidism: use Cinacalcet (a calcimimetic) and phosphate binders ie sevelamer Osteoporosis: Dexa > -2.5, use Ca, 1,25VitD Volume Overload: Use loops then when that fails use loops + metolazone and if that fails --> Hemodialysis Metabolic Acidosis: Keep Bicarb > 20, use NaBicarb From best to worst for bleeding: correct anemia, desmopressin, dialysis, estrogen, cryoprecipitate Acute Interstitial Nephritis (Tubulointerstitial Nephritis)
Acute interstitial renal inflammation Pyuria (classically eosinophils) and azotemia occurring after administration of drugs that act as haptens, inducing hypersensitivity (Diuretics, penicillin derivatives (including cephalosporins), proton pump inhibitors, sulfonamides, rifampin, NSAIDs Lead Less commonly may be 2° to other processes Systemic infections (eg, mycoplasma) or autoimmune diseases (eg, Sjögren syndrome, SLE, sarcoidosis) Associated with fever, rash, hematuria, and costovertebral angle tenderness, but can be asymptomatic Results in acute renal failure (intrarenal azotemia); oliguria; may become renal papillary necrosis Increased levels of eosinophils and IgE Edema and leukocyte infiltration of the interstitium Considered both an IgE mediated hypersensitivty and IV hypersensitivity WBC casts (WBC with Tamm-horsfall protein) C. Proteinuria Most commonly seen in females (peak at age 50-55 years, due to NSAID use) +/- Arthralgias Renal biopsy: Inflammatory infiltrate, edema Less commonly, AIN may be caused by infectious agents (eg, Legionella, Mycobacteriurn tuberculosis , Streptococcus) Since it is a hypersensitivity, withdrawal of the drug will resolve it +/- Systemic glucocorticoids Pyelonenphritis and amyloidosis can be causes Acute Tubular Necrosis
Most common cause of acute kidney injury in hospitalized patients Spontaneously resolves in many cases Can be fatal, especially during initial oliguric phase Necrotic cells plug tubules causing decrease in GFR Increased FENa Granular (“muddy brown”) casts (Pictured, A) Inciting event Maintenance phase - oliguric; lasts 1–3 weeks; risk of hyperkalemia, metabolic acidosis, uremia Increased creatinine/bun, fluid overload Edema, pulmonary edema, weight gain, high anion gap metabolic acidosis Often dialysis is used Recovery phase—polyuric; BUN and serum creatinine fall; risk of hypokalemia U. Less so but still important: hypophosphatemia and hypocalcemia; stage of re-epithelization Renal colic may occur following sloughing of renal papilla 2° to decreased renal blood flow (eg, hypotension, shock, sepsis, hemorrhage, HF, acute MI, surgery etc.) Results in death of tubular cells that may slough into tubular lumen (Pictured, B) (PCT and thick ascending limb are highly susceptible to injury) For hypoxic causes not nephrotoxic causes! 2° to injury resulting from toxic substances (eg, aminoglycosides, radiocontrast agents, lead, cisplatin), crush injury (myoglobinuria), hemoglobinuria Ethylene glycol (oxalate crystals) and rate (e.g., tumor lysis syndrome) PCT is particularly susceptible to injury; the renal medulla Ischemic kidney can be a cause Treatment: IV fluid prophylaxis (when the patient is given one of the toxins ie contrast, listed) Administration of IV diuretics may be used as part of treatment Tenofovir can be a cause Bun/creatinine ratio: Typically normal (~10 -15) Fractional excretion of sodium: >2% Urine osmolality: ~300 mOsm/kg Renal Papillary Necrosis
Sloughing of necrotic renal papillae (Pictured) Gross hematuria/proteinuria; flank pain May be triggered by recent infection or immune stimulus Associated with sickle cell disease or trait, acute pyelonephritis, NSAIDs, phenacetin, aspirin, diabetes mellitus, severe acute pyelonephritis Urinary tract obstruction is also associated White/yellow necrosis of the distal 2/3rds of the renal pyramids Diffuse Proliferative Glomerulonephritis
Nephritic Most common form of renal disease in SLE Due to SLE or membranoproliferative glomerulonephritis LM—“wire looping” of capillaries EM—subendothelial and sometimes intramembranous IgG-based ICs often with C3 deposition IF—granular A common cause of death in SLE DPGN and MPGN often present as nephrotic syndrome and nephritic syndrome concurrently Proliferation/thickening (look at the name) of cells (lymphocytes and endothelium) within the capillary loops U. Crescent formation during active part of disease Lung Development
Initial development includes development of lung bud from distal end of respiratory diverticulum during week 4 Lung bud divides into two bronchial buds that branch off into bronchi Lung bud to trachea to mainstem bronchi to secondary (lobar) bronchi to tertiary (segmental) bronchi Errors at this stage can lead to TE fistula Endodermal tubules to terminal bronchioles; Surrounded by modest capillary network Respiration impossible, incompatible with life Terminal bronchioles to respiratory bronchioles to alveolar ducts. Surrounded by prominent capillary network Airways increase in diameter; Respiration capable at 25 weeks Alveolar ducts to terminal sacs. Terminal sacs separated by 1° septae. Pneumocytes develop Terminal sacs to adult alveoli (due to 2° septation) View More
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