Case 5 B7

what are the five major renal tubular defects and what part of the nephron do they affect

"Fanconi is First," the rest are in alphabetical order -Fanconi: proximal convoluted tubule -Bartter: thick ascending limb in loop of Henle -Gitelman: distal convoluted tubule -Liddle: collecting duct -SAME: collecting duct

describe the physiologic function of the proximal tubule of the nephron

-100% glucose & amino acids -67% water, bicarb, NaCl, K+, phosphate (PTH inhibits Na+/phos cotransport here > ↑ phos excretion) basolateral Na+/K+ ATP-ase (energy source): -keeps low Na+ inside cell to drive transporters -SGLT-2: Na+/glucose symporter -site of action of SGLT-2 inhibitors -glucose into blood via GLUT1/2 (not pictured) Basolateral K+/Cl- symporter: -pulls out the K+ that was pumped in by the ATPase -driving force for Cl- to be reabsorbed -this powers the Cl-/Anion exchanger via charge so we excrete OH-, formate, oxalate, sulfate Na+/amino acid transporters: -reabsorb all AAs (not shown) -clinical: Hartnup disease = no tryptophan transporter here biccarb: Carbonic Anhydrase -bicarb in lumen combines with H+ > H2CO3 > CO2 + H2O via CA > simple diffusion into cell > back to H2CO3 via CA > HCO3- + H+ -H+ recycled using Na+ antiporter to perform same process -HCO3- absorbed into interstitium using Na+/HCO3- symporter. -final result: Na+ and HCO3- get into the blood -site of acetazolamide action -AT II stimulates Na/H+ exchange > increases Na+, H2O, and HCO3- reabsorption -clinical: type II RTA = inability to absorb bicarb via this mechanism > metabolic acidosis -water reabsorbed paracellularly (not pictured): driving force is high Na+ and Cl- in the interstitium/blood -clinical: Fanconi syndrome (overall dysfunction of PCT)

describe renal blood flow & mechanisms that control it

-25% of cardiac output reaches the kidneys what signals mediate renal blood flow: -sympathetic nervous system signaling: decrease RBF, alpha 1 receptors induce afferent arteriolar vasoconstriction (hypovolemic shock induced acute kidney injury) -angiotensin 2: decrease RBF; at low concentrations preferentially efferent, at higher concentrations it constricts both -ANP: dilates both afferent and efferent -prostaglandins: dilate both afferent and efferent arterioles, good at antagonizing sns and ang 2 in acute hemorrhage > unopposed constriction is bad (NSAIDS block protective prostaglandins effect) -dopamine: dilate renal arterioles

describe acute poststreptococcal glomerulonephritis

-AKA postinfectious glomerulonephritis (newer name) -NOTE: different than infection-related glomerulonephritis -Type III hypersensitivity reaction (deposition of Ab-Ag complexes) -hematuria (tea/cola colored urine), oliguria, periorbital edema, HTN -presents ~2-4 weeks after GAS (S. pyogenes) infection of the skin (impetigo) OR pharynx (pharyngitis) -only if a nephritogenic strain—aka, has M protein virulence factor (but caused by abs against SpeB) -What postinfectious sequelae can GAS skin infections NOT cause? Rheumatic fever! -can be caused by non-streptococcal organisms too -more commonly seen in children; sometimes adults -labs: + strep titers/serologies, ↓ complement (C3) d/t consumption -Type II RPGN (along with lupus nephritis) - granular IF -light: enlarged, hypercellular glomeruli; mono and neutrophilic infiltration, mesangial and endothelial proliferation -IF: "starry sky" granular BM deposits of IgG, IgM, C3 (lumpy, bumpy) - diffuse and global -EM: subepithelial "humps" (immune complexes) -treatment: supportive -children rarely progress to RF, (1%) up to 25% of adults develop RPGN

list causes of proximal RTA

-Fanconi syndrome -multiple myeloma -carbonic anhydrase inhibitors

describe Hep C

-Flavivirus (mostly mosquito illnesses) -enveloped, (+) ssRNA, linear, icosahedral -high degree of antigenic variation envelope glycoproteins: -contain a "hypervariable region" -high mutation rate in genome -lack of proofreading by viral RNA polymerase -result: prone to frequent mutations -difficult for immune system to eradicate effectively -high rate of chronic disease -mostly acquired through IVDA or transfusion (transfusion illness now rare due to screening) -rare cases from needle sticks, sexual contact acute illness: -usually asymptomatic & usually leads to chronic disease chronic infection: -usually asymptomatic or mild, nonspecific symptoms -often incidental discovery of abnormal LFTs -screening done for high risk patients (IVDA)

list factors that control GFR

-GFR = Kf (Pglom cap - Pbow space) - oncotic pressure -afferent arteriolar constriction > lowers GFR by lowering hydrostatic pressure (sympathetic nervous system activity) -efferent arteriolar constriction > raises GFR by raising hydrostatic pressure > angiotensin 2 -pressure in Bowman's capsule also affect GFR > if the hydrostatic pressure in Bowman's space is high than plasma won't diffuse across -low plasma protein content > raises GFR as there if high fluid concentration in the capillary flowing outward

describe the relationship between GFR & inulin clearance

-GFR is a marker of glomerular function > how is the kidney parenchyma function -inulin is the ideal marker for assessing GFR -inulin is a fructose polymer that is freely filtered and is neither absorbed or secreted -GFR = [U inulin] * V/[P inulin] = Cl inulin -since inulin is neither absorbed or secreted GFR is equal to inulin clearance

what stains may be used to evaluate a kidney biopsy via light microscopy

-H&E -PAS -silver -trichrome

how is Hep C diagnosed

-HCV RNA by PCR: elevated soon after exposure -anti-HCV: elevated by 12 weeks after exposure -both elevated in chronic disease (common)

describe hepatitis B presentation

-Hepadnavirus family (DNA virus) -enveloped, circular, icosahedral capsid -#1 (partially double stranded DNA virus): genome enters hepatocytes > nucleus > DNA becomes fully double stranded > mRNA synthesized > cytoplasm -#2 (reverse transcriptase synthesized): viral mRNA > viral DNA > packaged in capsid -#3: envelope from endoplasmic reticulum -sexual contact -IV (drug use, transfusion, needle stick) -maternal-fetal: especially if mother gets acute disease 3rd trimester, babies usually have minimal symptoms, lots of viral replication in baby (immature immune system); babies at HIGH risk of progression to chronic disease -incubation of 1 to 4 months -acute infection: 70% have subclinical or mild hepatitis (anicteric), 30% icteric hepatitis

describe hepatitis E

-Hepevirus -non-enveloped, (+) ssRNA, linear, icosahedral -outbreaks worldwide in resource-limited areas -infection from fecal contamination of water -self-limited acute infection - no chronic infection -diagnosis: HEV genome in in serum or feces (PCR); IgM antibodies to HEV -pregnancy: hepatic failure more frequent during pregnancy (high mortality rate, 15 to 25%)

what markers might we be looking for if examining a kidney biopsy using immunofluorescence

-IgA, IgG, IgM, C3, C1q -fibrinogen, albumin, kappa and lambda

describe hepatitis A

-Picornavirus -non-enveloped, (+) ssRNA, linear, icosahedral -synthesize a large polypeptide -cleavage → viral proteins -transmitted through personal contact, drinking contaminated water, consumption of raw sea food -common in underdeveloped countries (poor hygiene and sanitation) -classic case: traveler to Mexico, Central/South America -incubation period ~30 days -diagnosis of acute disease: anti-HAV IgM antibodies plus symptoms -diagnosis of prior disease: anti-HAV IgG antibodies -self-limited; no specific therapy -acute disease only - no chronic infection -often asymptomatic (antibody tests done later may show anti-HAV IgG) -inactivated virus vaccine available (IM) -part of US routine childhood vaccination schedule

describe rapidly progressive (crescentic) glomerulonephritis

-a clinical term: different etiologies can cause it -nephritic syndrome w/ acute renal failure -oliguria, rapid increase in Cr, etc (w/o treatment complete failure in weeks-months; FA: days-weeks) -biopsy: crescents in Bowman's space comprised of fibrin, plasma proteins (C3b), glomerular parietal cells (they proliferate), monocytes, macrophages) > filtration blocked -etiologies divided into 3 types; distinguished by immunofluorescence pattern Type I: anti-GBM (linear) -w/ alveolar hemorrhage = Goodpasture -w/o alveolar hemorrhage = anti-GBM GN Type II: Immune complex GN (granular) -lupus nephritis: diffuse proliferative glomerulonephritis (can also be secondary to HSP or Cryo) -PSGN (post-streptococcal) -IgA nephropathy (rare to cause acute GN though) -idiopathic -complicating primary GN Type III: Pauci-immune GNs (ANCAs) - no IF -Wegener granulomatosis (c-ANCA) -microscopic polyangiitis (p-ANCA) -Churg-Strauss syndrome (eosinophilic polyangitis) w/ p-ANCA -renal limited vasculitis

what is Tanner staging

-a sexual maturity rating (SMR) scale used to assess the development of secondary sexual characteristics (e.g., breast, genital, pubic hair development) in both males and females -breast development (girls) -genital development (boys) -pubic hair development (boys and girls) note: testes descend by 6 months of age

what ddx should be considered when cirrhosis is suspected

-acute fatty liver of pregnancy -Amanita phalloides mushroom poisoning -acetaminophen poisoning -bacillus cereus toxin -fructose intolerance -galactosemia -HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome of pregnancy -hemorrhage viruses (Ebola, Lassa, Marburg) -idiopathic drug reaction -neonatal iron storage diseases -tyrosinemia

list common undesired side effects of antibiotics

-allergic reactions -nausea -vomiting -diarrhea -black hairy tongue -CNS effects -increased BMI in children

list causes of distal RTA

-amphotericin B toxicity -analgesics -obstructive urinary congenital anomalies -autoimmune diseases (SLE)

describe Goodpasture syndrome

-antibodies against alpha 3 portion of type IV collage in basement membrane of alveoli and glomeruli -hematuria, hemoptysis -Type II hypersensitivity reaction: associated with exposure to hydrocarbon solvents, viruses, drugs, cancer -classically in young adult males -HLA-DRB1 predisposition -Type I RPGN: linear IF biopsy: -LF: hypercellularity, crescents -IF: linear BM staining with IgG and C3 -EM: BM disruption, no immune complex deposition -treatment: plasmapheresis (but poor prognosis)

describe arteriole:venule ratios

-arteriole narrowing is associated with high BP & age -normal A:V ratio = 2:3 - 3:4 (artery diameter < 66-75% of vein diameter) - ratio < 66% can indicate hypertensive changes

what gene mutation is responsible for Liddle syndrome

-autosomal dominant -ENaC subunit gene: SCNN1A/1B/1G/1D -rare -gain of function mutation

which gene is mutated in SAME (Syndrome of Apparent Mineralocorticoid Excess) and what does it code for

-autosomal recessive -loss of function in HSD11B2 gene -codes for 11β-HSD, which normally converts cortisol to cortisone (increased cortisol:cortisone ratio characterizes the condition) -extremely rare

what is the difference between diffuse & focal glomerular diseases

-based on number of affected glomeruli (in the kidney) -diffuse: >50% glomeruli affected -focal: <50% glomeruli affected

describe the window period during hep B infection

-brief period where: (1) HbsAg undetectable (2) anti-HBsAg not yet detectable -can give false appearance of no infection -SOLE marker of infection is anti-HBc (IgM)

what complications can result from otitis externa

-canal stenosis -hearing loss -periauricular cellulitis -osteomyelitis of temporal bone

what are the potential sequelae of chronic Hep C infection

-cirrhosis -liver failure (common indication for transplant) -hepatocellular carcinoma

how is otitis externa treated

-clean ear canal: remove cerumen and exudate w suction or hook, rinse w/ NS > to be done by doc, ideally otorhinolaryngologist (not pt/parents) -topical antiseptic + antimicrobial treatment + steroid drops (common: polymyxin B + neomycin + hydrocortisone drops) -adequate analgesia: ibuprofen or acetaminophen -systemic abx only needed if: infection spreads beyond ear canal, poorly controlled DM, immunosuppression, topical treatment not possible

list the causes of otitis media

-coinfection with both bacterial and viral pathogens is common (∼ 66% of cases) -less commonly (27% of cases): solely a bacterial infection -purely viral AOM is rare (< 5%); cases are usually mild and self-limiting bacteria: -Streptococcus pneumoniae -Hemophilus influenzae -Moraxella catarrhalis viruses: -respiratory syncytial virus -parainfluenza virus -influenza virus -rhinovirus -adenovirus

describe the clinical presentation of cirrhosis

-compensated: asymptomatic for long periods (compensated) -insidious or abrupt (less common) onset (decompensated) elevation in: -ALT (alanine aminotransferase) -AST (aspartate aminotransaminase) -GGT (gamma-glutamyl transferase) -ALP (alkaline phosphatase): in cholestatic disorders -PT: coagulation factor defects/deficiency -immunoglobulins: impaired clearance by liver -low albumin (decreased synthesis in liver) -edema -infections -hepatocellular carcinoma -liver nodules on US/CT/MRI/liver biopsy

explain the pathophysiology of SAME

-cortisol can bind mineralocorticoid receptors, basically stealing aldosterone's job ("cortisol tries to be the SAME as aldosterone") -to prevent this, target cells for aldosterone express 11β-HSD -11β-hydroxysteroid dehydrogenase (11β-HSD) converts cortisol > cortisone (which cannot bind mineralocorticoid receptors) -also caused by glycyrrhetinic acid in licorice > blocks 11β-HSD -end effect: increased mineralocorticoid effects NOTE: -aldosterone binds other receptors that cortisol can't, so pathophys is not as simple as MR hyperfunction

describe the relationship between creatinine, inulin, & GFR

-creatinine is the closest product we have to inulin -all filtered creatinine is excreted > a small amount is secreted thus it is a slight over estimation of GFR and people produce different amounts of creatinine based on weight age, and sex -Crockoft Gault equation to normalize: CrCl = (140 - age)*(Wt in kg)*(.85 if the patient is female)/72*Cr -since the amount of creatinine produced is equal to the amount in the urine we can assume that [U Cr] * V is a constant -so plasma Cr is a good marker of GFR -normal 0.8 mg/dL -CKD 2.0 mg/dL -ESRD 4.0 mg/dL

describe the management of cirrhosis

-damage is permanent (in general) prevent further damage to liver: -address underlying etiology: may need antiviral medications, steroids, immunosuppressants, copper/iron chelation -avoid alcohol -HBV/HCV vaccination -good nutrition -weight reduction -early treatment of precipitating factors like dehydration, hypotension, infections

explain the defect in proximal RTA

-defect in PCT HCO3- reabsorption > increased excretion of HCO3- in urine > metabolic acidosis -urine pH < 5.5 when plasma HCO3- is below resorption threshold, & > 5.5 when filtered HCO3- exceeds resorptive threshold -↓ serum K+ (decreased HCO3 reabsorption causing increased flow rate to distal tubule and causing increased K excretion)

describe the metanephros

-develops from the uretic bud, an outgrowth of the mesonephric duct -the uteric bud caudal growth of the nephrogenic cord -merges with the metanephric blastema around week 6 -the distal portion of the bud branches and differentiates into the collecting tubules: the first portion forms major calicies & the later portions form minor calicies (this occurs weeks 7 and 8)

describe the mesonephros

-develops prior to the pronephros regressing and develops caudally to the pronephros -the mesonephric kidney contains glomeruli which are connected to mesonephric tubules > the mesonephric tubules open onto the mesonephric duct -they will function for about 4 weeks while the metanephros (primordial kidney) develops

explain the significance of plasma 18-oxocortisol and 18-hydroxycortisol

-differentiate aldosteronoma from bilateral hyperaldosteronism in pts w/ primary hyperaldo -levels are notably elevated in aldosteronomas vs bilateral -hybrid steroids; urinary excretion is (slightly) increased in primary hyperaldosteronism -source of precursors not clear > chemically complicated synthesis

list the causes of MN (from lecture)

-drugs: penicillamine, captopril, gold, NSAIDS -cancers: lung, colon, melanoma -SLE: 10-15% of lupus glomerulonephritis -infections: chronic Hep B/ Hep C, syphilis, schistomiasis, malaria -other autoimmune disorders: such as thyroiditis

describe cirrhosis epidemiology

-end-stage liver damage -characterized by fibrosis and regenerative nodules -unknown prevalence worldwide -US prevalence: 0.15-0.27% -11th leading cause of death globally -8th leading cause of death in US

glomerulus structure

-epithelium (parietal) -urinary space -epithelium (visceral) with podocytes (foot processes) -basement membrane (GBM) w/ filtration across this membrane -endothelium (vascular); blood is here

describe thin basement membrane disease

-fairly common hereditary nephritis: mutation in alpha 3 and 4 gene of type IV collagen -recurrent asymptomatic hematuria (think of as on a spectrum w/ Alport's) -NO hearing loss or ocular abnormalities -EM: diffuse thinning of GBM

what is renal tubular acidosis

-fefers to renal disorders that occur due to removal of HCO3- or acid handling in the presence of preserved GFR -c-auses normal anion gap metabolic acidosis -anion gap (8-12 mEq/L is normal) = Na+ - (Cl- + HCO3-) -4 subtypes

describe basic renal anatomy

-fiborous Capsule -cortex: PCT, DCT, glomerulus -medulla: collecting duct, loops of Henle, Vasa recta -renal blood flow: abdominal aorta > renal a > segmental a > interlobular a > cortical radial a > afferent arterioles > glomerular capillaries > efferent arterioles > vase recta capillaries > venous circulation

describe the clinical presentation of Fanconi syndrome

-generalized reabsorption defect in PCT → ↑ excretion of amino acids, glucose, HCO3-, and PO43- effects: metabolic acidosis (proximal RTA), hypophosphatemia (growth retardation, rickets/osteopenia), hypokalemia, volume depletion

what is glucocorticoid remedial aldosteronism

-genetic cause of pseudo-hyperaldosteronism -autosomal dominant -<1% of cases of primary aldosteronism -aldosterone synthesis is under control of ACTH -testing: low-dose dexamethasone ACTH suppression test -treat w either long-term dexamethasone OR aldosterone antagonists (spironolactone)

describe the hepatitis B antigen (HBsAg)

-hallmark of infection -glycoprotein that forms spheres and tubules (EM) -from surface of envelope -detectable weeks after exposure, prior to symptoms -recovery from acute hepatitis > HBsAg becomes undetectable after four to six months -chronic infection > persistence of HBsAg for more than six months -prior infection or vaccination > presence of anti-HBsAg antibodies without HBsAg -generally, when anti-HBsAg levels rise, HBsAg levels fall and infection clears note on the hep B vaccine: -contains recombinant HBsAg -vaccinated individuals will be + for anti-HBsAg -all other antibodies (HBc, HBe) should be negative

list causes of Fanconi syndrome

-hereditary defects: Wilson's disease, tyrosinemia, glycogen storage diseases -ischemia -multiple myeloma -drugs: cisplatin, tenofovir, expired tetracyclines, ifosfamide -lead poisoning

describe this biopsy (top image is normal); does it indicate a nephrotic or a nephritic syndrome

-hypercellular -inflamed glomeruli this is a nephritic syndrome

explain the defect in hyperkalemic RTA

-hyperkalemia caused by hypoaldosteronism or aldosterone resistance > decreased NH3 synthesis in the PCT > decreased NH4 excretion -urine pH < 5.5 (but can vary)

what glomerular features might we be looking for on a kidney biopsy using EM

-immune-complex deposits -foot processes -basement membrane thickness -amyloidosis

describe the physiologic function of the thin descending loop of Henle

-impermeable to NaCl -concentrates urine: water leaves urine; drawn out by hypertonicity in medulla -high osmolarity in interstitium to draw out water is created by Na, Cl, and urea: urea resorption in the collecting duct is *essential* to maintain these gradients for water resorption -urine eventually equilibrates with interstitium at transition from descending to ascending limb (~1200 mOsm)

describe the physiologic function of the thick ascending loop of Henle

-impermeable to Water -Na+/K+ ATPase still present •Na+/K+/2Cl- symporter -site of loop diuretic action -K+ leak channel present > K+ back into lumen > pos charge repels other pos ions > Mg2+ and Ca2+ resorption via paracellular route -overall resorption of Na+, K+, and Cl- > urine becomes dilute again -10-20% Na+ absorbed here

explain the defect in distal RTA

-inability of alpha-intercalated cells to secrete H+ > no new HCO3- is generated > metabolic acidosis -urine pH > 5.5 -decreased serum K+ d/t failure of H/K ATPase

what happens when aldosterone binds it's receptor (AR for aldosterone receptor or MR for mineralocorticoid receptor)

-increased ENaC & Na+/K+ ATPase expression -electrogenic gradients change: Na+ in, K+ & H+ out

list symptoms of acute otitis media

-inflammation of the middle of the ear -otalgia (present in approx. 80% of patients) -otorrhea -fever (present in 30-60% of patients, rarely >104ºF) -can also have non-specific symptoms such as headache, nausea, vomiting, diarrhea -antecedent/concurrent URI symptoms present in many patients

what mutation causes mixed RTA

-inherited mutations in carbonic anhydrase II -very rare combination of types 1 and 2

what are the treatment options for Hep C

-interferon -ribavirin -others

what do square/circle & black/white mean on a pedigree

-male = square -female = circle -solid/black = has trait -open/white = does not have trait

list symptoms of acute hepatitis

-many acute infections asymptomatic -fever, malaise, nausea, vomiting, anorexia -RUQ pain -jaundice (yellow skin from bilirubin) -itching (bile salts in skin) -dark urine (bilirubin) -clay-colored stools (lack of bilirubin excretion)

list physical exam findings that indicate otitis media

-middle ear effusion: fullness/bulging of tympanic membrane (best indicator), and/or reduced/absent tympanic membrane mobility on insufflation -erythematous or cloudy tympanic membrane -pus behind tympanic membrane -tympanic membrane perforation

list the five high-yield nephrotic syndromes for this block

-minimal change disease -focal segmental glomerulosclerosis (FSGS) -membranous glomerulonephritis -diabetic nephropathy -amyloidosis

describe IgA nephropathy (Berger disease)

-most common cause of GN in the world -IgA immune complex deposition in mesangium of glomerulus (predominantly nephritic with recurrent hematuria) -presents during childhood as episodic gross or microscopic hematuria with RBC casts, usually following mucosal infections > IgA production is increased during infection (also associated with celiac disease) -renal pathology of IgA vasculitis (Henoch-Schonlein purpura) Type II RPGN (although rare to cause this!) - granular IF -light: mesangial proliferation; can also look normal; can also present with crescents -IF: IgA based immune complex deposits and C3 deposition in mesangium - granular -EM: mesangial immune complex deposits -prognosis: may progress to renal failure in 25 years

describe diffuse proliferative glomerulonephritis

-most common type of SLE renal disease (lupus nephritis) -often both nephritic AND nephrotic (along with MPGN) -Type II RPGN - granular IF biopsy: -light: varied; "wire loop" capillaries ("wire loopus") -IF: granular (IgG, IgA, IgM, C3, C1q staining); PSGN is more common cause of granular IF -EM: immune complex deposition (IgG based) in mesangial subendothelial, and subepithelial regions often with C3 deposition

describe the epidemiology of acute otitis media

-most commonly occurs in ages 6-18 months: 60-80% of patients had AOM by 1 year, 80-90% of patients had AOM by 3 years -most common reason for antibiotic use in children -responsible for 16 million office visits in 2000 > 80% of these visits led to antibiotic prescription

when and how should otitis media be treated

-most important treatment in children is symptomatic (severe) -treat fever > acetaminophen or ibuprofen -treat otalgia > acetaminophen or ibuprofen -intra-otic therapy > antipyrine-benzocaine drops -amoxicillin is the first-line antibiotic

describe coarctation of the aorta

-narrowing of aorta -preductal (infantile): most common, narrowing is proximal to ligamentum arteriosum/ductus arteriosus -postductal (adult): narrowing is distal to ligamentum arteriosum -most often occurs distal to the left subclavian artery branch -causes increased upper extremity BP -can also see R arm BP > L arm if origin of left subclavian artery is involved -higher risk of essential HTN even after surgery (HTN management key in post-surgical pts)

disruption of mainly what structure characterizes nephrotic & nephritic syndromes respectively

-nephrotic = podocyte disruption (podocyte damage → no charge barrier → proteins leak through → proteinuria) -nephritic = GBM disruption (GBM inflammation/damage → RBCs leak through → hematuria) some pathologies can cause both!

what conditions are associated with mixed RTA

-osteopetrosis-cerebral calcifications-mental retardation -bone fractures -growth failures

describe the physiologic function of the collecting tubule

-overall: (1) resorbs H2O, Na+ (aldosterone and ADH) (2) secretes K+ and H+ (aldosterone) (3) urea absorption -the more Na+ you deliver here, the more K+ you will excrete (why hypokalemia in loops/thiazides) -3-5% Na+ absorbed here principal cells -Na+/K+ ATPase ultimately causes Na+ to be drawn in, K+ to be pushed into the lumen -promoted by aldosterone (blocked by MRAs spironolactone/eplerenone) -aldosterone > ↑ Na+/K+ pumps, ↑ ENaC activity > ↑ lumen negativity > K+ secretion •ENaC site of Amiloride, triamterene action in principle cells, aquaporin 2 channels reabsorb water -ADH binds V2 receptors (cAMP) to increase #s of AP2s in the membrane > ↑ permeability of cells to water -ADH also increases the #s of urea transporters alpha-intercalated cells -H+ secreted into lumen (how we can eliminate acid from the body) -promoted by dldosterone (blocked by MRAs spironolactone/eplerenone) -lumen negativity > H+ ATPase activity > H+ secretion > HCO3−/Cl− exchanger activity B-intercalated cells -HCO3- /Cl- exchanger

describe the physiologic function of the early distal convoluted tubule

-overall: resorbs Na+, Cl- -impermeable to H20 > makes urine fully dilute (5-10% Na+ reabsorbed here) Na+/K+ ATPase stil here Na+/Cl- symporter: -site of action of thiazide diuretics -Ca2+, Mg2+ can also diffuse into the cell -Ca2+ then transported into the interstitium in exchange for Na+ -PTH can act here to increase the resorption of Ca2+ (↑ Ca2+/Na+ exchange) -also a Cl- diffusion channel > Cl- into interstitium

describe membranoproliferative glomerulonephritis

-pathoma calls this a nephrotic syndrome; FA and lecture call it nephritic (overall, can be nephritic, nephrotic, or both!); generally Type I can be either, but type II is more nephritic -thickened glomerular basement membrane due to immune complex deposition (mesangial ingrowth > GBM splitting > tram tracking) -2 types based on location of deposits Type I: subendothelial -classical complement pathway; will have ↓ serum C3 -can be primary or secondary (HBV, HCV, HIV, cancer, SLE, endocarditis) Type II: intramembranous -aka dense deposit disease -alternative complement pathway -assoc. with C3 nephritic factor, an autoantibody that stabilizes C3 convertase, leading to overactivation of complement, inflammation, and ↓ circulating C3 -poor response to steroids, progresses to chronic renal failure -high recurrence in transplants

describe systemic amyloidosis (amyloid nephropathy)

-pathophys: amyloid deposits in the kidney (the body's filter) -triggers are any cause of amyloidosis: multiple myeloma, AL amyloid, AA amyloid, B2-microglobulin -biopsy findings: mesangial thickening! -light: Congo red positive, apple green birefringence (polarized light) -fluorescence: AL amyloid → kappa or lambda positive -EM: randomly arranged fibrils

describe minimal change disease (MCD, lipid nephrosis)

-pathophys: idiopathic/cytokine mediated damage (triggers: infection, immunization, immune stimulus) biopsy findings: -light: normal, sometimes lipids in the PCT -fluorescence: nothing -EM: podocyte effacement -epidemiology: most common nephrotic in kids ): -treatment: excellent response to steroids [EM images showing podocyte effacement]

describe focal segmental glomerulosclerosis

-pathophys: idiopathic/poorly understood (causes: HIV, SCD, heroin, obesity, interferons) biopsy findings: -light: segmental sclerosis -fluorescence: nothing -EM: podocyte effacement, mesangial expansion -epidemiology: most common in adults (Black, Hispanic, overall) -treatment: poor prognosis, can progress to CKD

describe diabetic nephropathy

-pathophys: non-enzymatic glycosylation → mesangial deposition of extracellular matrix; hyperfiltration → sclerosis -biopsy findings: Kimmelstiel-Wilson nodular sclerosis -light: GBM and mesangial thickening -fluorescence: nothing! -EM: GBM and mesangial thickening -epidemiology: common in untreated diabetes -other: most common cause of ESRD in USA

describe membranous nephropathy (membranous glomerulonephritis)

-pathophys: primary: anti-PLA2 antibodies (other: drugs like NSAIDs, infections like HBV/HCV/syphilis, SLE, tumors) biopsy findings: -light: capillary/GBM thickening -fluorescence: granular (immune complex deposition) -EM: subepithelial deposits ("spike + dome") -epidemiology: most common nephrotic in Caucasian adults -other: poor prognosis, can progress to CKD

list the high-yield nephritic syndromes for the block

-post-infectious glomerulonephritis (First Aid specifically has "acute poststreptococcal glomerulonephritis, PSGN") -IgA nephropathy (Berger disease) /Henoch-Schönlein purpura nephritis (HSP nephritis) -lupus nephritis -anti-GBM disease (Goodpasture syndrome) -Pauci-immune glomerulonephritis (c-ANCA & p-ANCA) -membranoproliferative glomerulonephritis (MPGN) -rapidly progressive (crescentic) glomerulonephritis (RPGN) -thin basement membrane disease -Alport's syndrome First Aid has Goodpasture & Pauci listed as subcategories of RPGN

describe workup to determine the cause of hyperaldosteronism

-primary tests are plasma renin conc. (PRC) and plasma renin activity (PRA): low/undetectable in primary, high in secondary -PAC/PRA ratio is confirmatory test for primary hyperaldosteronism: PAC/PRA ratio >30 with PAC > 20 has sensitivity and specificity >90% (should also undergo imaging to rule out large masses/carcinomas) -can also use aldosterone suppression test (oral sodium loading over three days) > urine aldo should decrease, normally

what is the difference between proliferative & membranous glomerular diseases

-proliferative: hypercellularity -membranous: membrane thickening

describe the clinical presentation of Bartter syndrome

-reabsorption defect in thick ascending loop of Henle (affects Na+/K+/2 Cl- contransporter) -autosomal recessive -effects (similar to loop diuretics): metabolic alkalosis, hypokalemia, hypercalciuria

describe the clinical presentation of Gitelman syndrome

-reabsorption defect of NaCl transporter in DCT -autosomal recessive -effects (similar to thiazide diuretics): metabolic alkalosis, hypomagnesemi, hypokalemia, hypocalciuria -less severe than Bartter syndrome

describe embryological renal development

-renal development begins at 4 weeks -the developing embryo contains 3 cell types: ectoderm, mesoderm, and endoderm -the mesoderm gives rise to the what will become the urogenital system and contains three subtypes: paraxial mesoderm (vertebral column), intermediate, and lateral plate mesoderm -intermediate mesoderm develops into the nephrogenic cord, which will become urinary structures

is primary or secondary hypertension more common in children & adolescent

-secondary is more common in children -primary is more common in adolescents

describe the epidemiology & presentation of primary hyperaldosteronism

-seen in 10% of hypertensive pts presents most commonly with: -first-occurrence and resistant HTN (fatigue, headache, polyuria, polydipsia) -metabolic alkalosis, hypokalemia, mild hypernatremia -asymptomatic, depending on HTN + comorbidities

what are the symptoms of otitis externa

-severe otalgia worsened by pressure on tragus or tension on pinna -otorrhea, itch, erythema, swelling of ear canal

describe hepatitis D

-small enveloped (-) RNA virus, circular genome -"defective virus" -lacks genes for envelope proteins -uses HbsAg for envelope protein -genome encodes one protein: delta antigen (HDAg) -virus particles carry HDAg pathogenesis: invades hepatocytes > travels to nucleus to replicate > uses HBV to provide envelope > virus particle coated with HBsAg > uses host cell RNA polymerase to replicate genome transmission: -co-infected with HBV -HDV infection in setting of chronic HBV carrier state -superinfection often leads to flare of hepatitis diagnosis: -serum HDAg -HDV RNA -anti-HDV antibodies note: Hep B vaccine protects against Hep D

describe nephron development

-some metanephric mesenchymal cells undergo mesenchymal to epithelia transition and form the nephron occurs via cell signaling from the collecting tubule -renal vesicles connect to the collecting duct -the end that connects to the collecting duct will be theDCT and the other end is the glomerulus

what are the three possible locations for deposits in nephrotic syndromes

-subepithelial -intramembranous -subendothelial

explain the relationship between PAH (para-aminohippurate), the FIck principle, & RPF

-the Fick Principle states that the amount of a given substance entering an organ is the same as the amount that leaves an organ so far as it isn't synthesized or degraded by that organ -amount of PAH entering the kidney = amount leaving -amount entering = [renal a. PAH] * RPF -amount leaving = [renal v. PAH] * RPF + [Urine PAH] * V (where V is urine flow) -RPF = [U PAH] * V/ [RA PAH] - [RV PAH] -para-aminohippuric acid is a great assessment of renal plasma flow (it is not synthesized by the kidney, it has no affect on RPF, the kidney extracts nearly all of PAH) -so, RPF = [U PAH] * V/ [P PAH]

describe the glomerulus

-the glomerular filtration structure is a multilayered system desiged to help us keep a large portion of what we want and get rid of what we need to excrete in the urine endothelial layer: -fenestrated capillaries with pores 70-100 nanometers in diameter -most plasma products can go through these pores, but erythrocytes and other blood cells cannot basement membrane -a three-layered membrane that blocks the crossing of plasma proteins due to charge-charge interactions (small solutes can bypass this) glomerular epithelium/ podocytes: -25-60 nm thin diaphragms

describe the pronephros

-the pronephros develops from the nephrogenic cord at the beginning of week 4 -two key structures develop: pronephric duct: (duct that runs down nephrogenic cord and enters the cloaca) & the nephrotome (small tissue protrusions) -does not begin producing urine until the end of week 4

describe Alport syndrome

-thinning and splitting of the glomerular basement membrane -inherited defect in type IV collagen (alpha 3, 4, 5 chains) - COL4A5 gene mutation; X-linked dominant (most commonly) -presents as isolated hematuria, sensory hearing loss, and ocular disturbances ("can't see, can't pee, can't hear a bee") -EM: basket weave appearance due to irregular thickening of GBM

explain how the kidney participates in acid-based regulation

-we need HCO3- as a buffer in our blood to maintain correct pH levels (non-volatile acids are produced as byproducts of metabolism > we can blow off CO2 but most everything else we have to neutralize) kidneys need to: #1: reabsorb/generate HCO3- -most reabsorption in PCT (carbonic anhydrase process): usually you excrete 0% of your bicarb -generation occurs in the collecting duct in a-intercalated cells > uses carbonic anhydrase again > must excrete that proton byproduct! #2: excrete H+ -really high H+ (from acidosis or bicarb generation) can damage the nephron > we need a buffer to protect against this! -however, we are using all of our HCO3- for serum buffering -for urinary buffers, we can use titratable acids (mostly phosphate) and ammonia (NH3, synthesized from glutamine)

what complication is specifically associated with distal RTA

-↑ risk for calcium phosphate kidney stones (d/t ↑ urine pH and ↑ bone turnover related to buffering)

what complication is specifically associated with proximal RTA

-↑ risk for hypophosphatemic rickets (Fanconi syndrome)

what are the components of the mnemonic "Autosomal DOMINANT Hunts Vulnerable Family"

1) Autosomal: ADPKD 2) D = dystrophia myotonica 3) O = osteogenesis imperfecta 4) M = Marfan syndrome 5) I = intermittent porphyria 6) N = neurofibromatosis type 1 7) A = achondroplasia 8) N = neurofibromatosis type 2 9) T = tuberous sclerosis 10) Hunts = Huntington's disease, hereditary spherocytosis 11) Vulnerable = vWD disease 12) Family = familial hypercholesterolemia

list potential lab findings with viral hepatitis

1) increased AST/ALT -ALT usually > AST -contrast with alcoholic hepatitis (AST>ALT) 2) increased bilirubin (direct) -liver can conjugate bilirubin in setting hepatitis -cannot transport into bile 3) false positive VDRL -viral hepatitis is common cause of false positive VDRL -don't confuse with syphilis

describe the three morphological classifications of cirrhosis

1) micronodular cirrhosis -uniform nodules less than 3 mm in diameter -caused by alcohol, hemochromatosis, hepatic venous outflow obstruction, & chronic biliary obstruction 2) macronodular cirrhosis -irregular nodules w/ a variation greater than 3 mm in diameter -caused by hep B/C, alpha-1-at deficiency, & primary biliary cholangitis 3) mixed cirrhosis -when features of both micronodular & macronodular cirrhosis are present -usually, micronodular cirrhosis progresses into macronodular cirrhosis over time

what are the extrahepatic manifestations of hepatitis B

1) polyarteritis nodosa -fevers, fatigue, arthralgias -abdominal pain, melena -neuropathy -rash 2) glomerular disease -most common is membranous nephropathy -presents as proteinuria, nephrotic syndrome

what are the stages of retinopathy

1) vasoconstrictive phase 2) sclerotic phase 3) exudative phase 4) hypertensive choroidopathy 5) hypertensive optic neuropathy

describe the prognosis associated with cirrhosis

10-year survival rate: -compensated: 47% -decompensated: 16% liver transplantation: -decompensated cirrhosis resistant to medical management - 1-year survival rate: 85% - 5-year survival rate: 72%

how much of the liver's blood supply comes from the portal vein

2/3

what organisms most commonly cause otitis externa

>90% of cases caused by Pseudomonas aeruginosa and Staphylococcus aureus

In this pedigree, none of the marriage partners from outside these two families are heterozygous for the trait. Indicate the genotype(s) of individual #3. NOTE: Some may have two possible genotypes) A) AA B) Aa C) aa

A) AA

Which of the following drugs is contraindicated in hereditary angioedema? A) ACE inhibitor B) spironolactone C) ARBs D) HCTZ

A) ACE inhibitor

Which of the following alkali mineral salts, used to treat GERD, causes constipation? A) aluminum hydroxide B) sodium hydroxide C) magnesium hydroxide D) potassium hydroxide

A) aluminum hydroxide

Which of the following mu opioid agonistss has the lower abuse potential? A) loperamide B) diphenoxylate

A) loperamide because loperamide cannot cross the BBB, but diphenoxylate can

describe Pauci-immune glomerulonephritis

ANCAs: -C-ANCA = Wegener granulomatosis -P-ANCA = microscopic polyangiitis and Churg-Strauss -Type III RPGN: no IF -typically not as fulminant as Goodpasture; patients are usually older too -light: different ages of crescents -IF: no immune deposits

In this pedigree, none of the marriage partners from outside these two families are heterozygous for the trait. What is the inheritance pattern for this trait? A) Autosomal dominant B) Autosomal recessive C) Sex linked dominant D) Sex linked recessive

B) Autosomal recessive

In this X-linked recessive trait pedigree, what is the genotype of individual #5? A) XHY B) XhY C) XhXh D) XHXh

B) XhY NOTE: this is standard format; for x linked recessive, H = normal and h = has recessive trait

Which of the following mood stabilizers causes hypothyroidism? A) valproate B) lithium C) carbamazepine D) lamotrigine

B) lithium

describe the 5 Tanner stages of breast development in girls

B1: -prepuberetal appearance & size -occasional elevation of the nipple B2: -enlarged mammary glands form a breast bud -slight increase in areolar diameter, nipple protrusion B3: -further enlargement of mammary glands -breast bud extends beyond the areolar diameter B4: -nipple & areolar form a secondary mound which projects above the breast tissue B5: -adult breast -areola with projection of papilla only

Which part of the nephron do thiazide diuretics work on? A) PCT B) collecting duct C) DCT D) Loop of Henle

C) DCT

Which of the following drugs is NOT first-line therapy for H.pylori infection? A) clarithromycin B) amoxicillin C) cimetidine D) omeprazole

C) cimetidine (an antihistamine)

Which of the following drugs directly inhibits primary active transport? A) empagliflozin B) verapamil C) omeprazole D) nicardipine

C) omeprazole

This pedigree tracks Duchenne Muscular Dystrophy (DMD) through several generations. DMD is an X-linked recessive trait. If individuals I-1 & I-2 had another son, what is the chance that he would have DMD? A) 0% B) 25% C) 50% D) 100%

D) 100%

Which of the following side effects can be caused by spironolactone? A) hyponatremia B) metabolic acidosis C) hyperkalemia D) gynecomastia

D) gynecomastia

Which of the following drugs will NOT block the peripheral converesion of T4 to T3? A) glucocorticoids B) beta blockers C) PTU D) methimazole

D) methimazole

Which of the following drugs is most likely to be used for maintenance of anesthesia? A) etomidate B) propofol C) ketamine D) thiopental

D) propofol

good nephron function summary diagram

Emma's student objective, slide 10, Lab 13, case 5

describe the 5 Tanner stages of genital development in boys

G1: -prepuberetal appearance and size of the testes, scrotum, & penis G2: -testicular volume of 4 mL -larger scrotum -penile growth has not begun -scrotal skin darkens in color & texture G3: -continued enlargement of the testes & scrotum -penile growth begins G4: -testicular volume of 12 mL -scrotum growth -penile growth continues: longer & wider penis -development of penis glans G5: -testes, scrotum, & penis attain adult appearance & proportions

which hepatitis is the only DNA hepatitis virus

Hep B

childhood vaccination schedule: 18 months - 18 years

KNOW THIS ON PEDS ROTATION

childhood vaccination schedule: Birth - 15 months

KNOW THIS ON PEDS ROTATION

what condition, also known as pseudohyperaldosteronism, presents like hyperaldosteronism but has very decreased aldosterone

Liddle syndrome "Liddle is LIke aldosterone, but aldosterone is Low"

compare the presentation of nephrotic & nephritic syndrome

Nephrotic presentation (PODOCYTE DISRUPTION): -[severe] proteinuria (> 3.5g/day ) -hypoalbuminemia -hyperlipidemia/lipiduria -edema Nephritic presentation (GBM DISRUPTION) -hematuria (with RBC casts & dysmorphic RBCs in urine) -hypertension -azotemia/oliguria (decreased GFR) -proteinuria (< 3.5 g/day) -salt retention with periorbital edema & HTN (d/t increased renin) can be immune complex mediated or not

how is Hep B DNA detected (and what is the main purpose of doing so)

PCR (major role is for determining viral load for treatment)

describe the 6 Tanner stagees of pubic hair development in girls & boys

Ph1: -usually no pubic hair, vellus hair possible Ph2: -sparse, lightly pigmented hair (straight or curled) on the labia/base of the penis Ph3: -dark, coarse, curlyl hair spreading over the pubic symphysis Ph4: -adult pubic hair that does not extend to the inner thighs Ph5: -adult pubic hair that extends to the innere thighs with horizontal upper border Ph6: -further growth of pubic hair along linea alba in the direction of the umbilicus

how is SAME treated and why

RECALL: aldosterone > binds the mineralocorticoid reeceptor (MR) > Na+ & HCO3- resorption, K+ & Cl- excretion -K+ sparing diuretic (amiloride or triamterene, ENaC antagonists) > ↓mineralocorticoid effects -spironolactone & epleronone won't work because they are aldosterone antagonists, which will have little effect if there is low aldosterone -however, can complement the effects of amiloride or triamterene -NOTE: amiloride is safest in pregnancy -exogenous corticosteroids (cortisone, hydrocortisone, prednisone) > ↓endogenous cortisol production > ↓mineralocorticoid receptor activation

is this biopsy consistent with Type I, Type II, & Type III rapidly progressive (crescentic) glomerulonephritis

Type I

is this immunofluorescent biopsy consistent with Type I, Type II, & Type III rapidly progressive (crescentic) glomerulonephritis

Type I (linear GBM deposits of IgG & C3)

how can biopsy distinguish between Type 1 & Type II MPGN

Type I: -light: mesangial cellularity and BM duplication (tram tracking): same for both type I and II; however, type I more associated with tram tracking -IF: granular membranous staining with IgG, C3, and +/- C1q -EM: subendothelial immune deposits Type II: -light: mesangial cellularity and BM duplication (tram tracking): same for both type I and II; however, type I more associated with tram tracking -IF: granular and linear membranous staining with C3 only -EM: intramembranous dense deposits

is this biopsy consistent with Type I, Type II, & Type III rapidly progressive (crescentic) glomerulonephritis

Type II

is this immunofluorescent biopsy consistent with Type I, Type II, & Type III rapidly progressive (crescentic) glomerulonephritis

Type II ("lumpy bumpy" granular pattern of staining)

is this biopsy consistent with Type I, Type II, & Type III rapidly progressive (crescentic) glomerulonephritis

Type III

is this immunofluorescent biopsy consistent with Type I, Type II, & Type III rapidly progressive (crescentic) glomerulonephritis

Type III (no immunoglobulin or complement deposits in GBM)

how is acute & chronic Hep B treated

acute hepatitis B: -usually treated with supportive care -immunocompetent adults <5% chance chronic disease multiple treatments for chronic disease: -interferon -Lamivudine (NRTI) -other antiviral drugs

name two serious potential sequelae of viral hepatitis

cirrhosis & hepatocellular carcinoma (note: alll cause liver inflammation)

what is the most common cause of portal htn in the world (what about in Africa)

cirrhosis (schistosomiasis in Africa)

describe the hepatitis B core antigen (HBcAg) & hepatitis B e antigen (HBeAg)

core antigen: -intracellular antigen (comes from within hepatocytes) -capsid core protein -expressed by infected hepatocytes -NOT detectable in serum -anti-HBc can be detected -anti-HBc IgM rises in acute infection -anti-HBc IgG prior exposure or chronic infection e antigen: -viral protein secreted by infected cells -part of capsid core -indicates significant viral replication > correlates well with levels of HBV DNA (HBsAg indicates presence of virus, not necessarily significant) -elevated in patients who are highly infectious -seroconversion to Anti-HBeAg usually associated with fall in viral DNA production

list causes of hyperkalemic RTA

decreased aldosterone production: -diabetic hyporeninism -ACE inhibitors/ARBs -NSAIDs -heparin -cyclosporine adrenal insufficiency aldosterone resistance: -K+ sparing diuretics -obstructive nephropathy -TMP-SMX

what are the most common causes of cirrhosis

developed world: -HCV -alcoholic liver disease -nonalcoholic steatohepatitis (NASH) developing world: -HBV -HCV others: -autoimmune hepatitis -primary biliary cholangitis -primary sclerosing cholangitis -hemochromatosis -Wilson disease -alpha-1 antitrypsin deficiency -Budd-Chiari syndrome -drug induced -chronic right HF -cryptogenic (unclear etiology)

Type 1 RTA is also known as what

distal RTA

describe portal hypertension

elevated pressure in the portal venous system -pressure gradient > 6 mmHg between portal and hepatic veins -clinically significant: > 10 mmHg caused by resistance to blood flow -veins do not have valves, so rely on pressure differential to enable blood flow through liver most frequent cause of hospitalization, variceal bleed, liver transplantation, and death in patients with cirrhosis diagnosis: -Doppler US (thrombosis) -symptoms (ascites) -direct: cannulation of hepatic vein and measuring pressure -indirect: balloon occlusion of hepatic vein and measurement of wedged hepatic vein pressure

what causes primary aldosteronism

excess production of adrenal gland (zona glomerulosa): -bilateral adrenal hyperplasia (60%) -primary tumor (Conn syndrome) (30%) -rarer: unilateral adrenal hyperplasia, ectopic aldo-secreting tumors, aldo-producing adrenocortical carcinomas, familial hyperaldosteronism type 1

what causes secondary hyperaldosteronism

excessive activation of RAAS: -renin-producing tumor -renal artery stenosis -edematous disorders: LVHF, pregnancy, cor pulmonale, cirrhosis

describe cirrhosis pathophysiology

hepatic stellate cells (HSCs): -form the wall of liver sinusoids & store Vit A -activated by inflammatory cytokines > transform into myofibroblasts > deposit collagen > fibrosis (mediated by TGF-Beta) sinusoidal endothelial cells (SECs): -form endothelial lining -make fenestrations in wall to facilitate fluid and nutrient exchange between sinusoids and hepatocytes -synthesize nitric oxide (NO) and endothelin-1 (ET-1) that act on HSCs (NO > relaxation of sinusoids, ET-1 > contraction of sinusoids) -chronic alcohol use leads to defenestration and promotes fibrosis Kupffer cells (KCs): -satellite macrophages -line the sinusoidal wall -release harmful mediators when exposed to injurious agents -act as antigen-presenting cells for viruses Hepatocytes: -release reactive oxygen species and inflammatory mediators when damaged cirrhosis: -increased ET-1 production & decreased NO production > increased intrahepatic vasoconstriction & resistance > portal htn > vascular remodeling by HSCs & formation of collateral circulation

Type 4 RTA is also known as what

hyperkalemic RTA

what does presence of HBsAg & anti-HBc in serum indicate

indicates chronic infection -is HBeAg is positive = high infectivity -viral DNA may be high or low (depending on viral load)

does the image show mild, moderate, or malignant hypertensive retinopathic changes (and why)

malignant: -lots of exudate/hemorrhages -optic disc swelling

does the image show mild, moderate, or malignant hypertensive retinopathic changes (and why)

mild: -generalized/focal arterial narrowing -AV nicking

Type 3 RTA is also known as what

mixed RTA

does the image show mild, moderate, or malignant hypertensive retinopathic changes (and why)

moderate: -flame hemorrhages -cotton wool spots -exudates

how can appropriate blood pressure for a child >1 be estimated based on age

normal systolic BP = (2 x age) + 90 -90th-95th percentile = preHTN -95th-99th percentile = HTN stage 1 - >99th percentile = HTN stage 2

Liddle Syndrome vs. SAME comparison table

notes SAME: -UpToDate: SAME can present with low birth weight, FTT, early severe hypertension w/ end organ damage, hypercalciuria of unknown origin, & kidney failure -Jounal of Clinical Hypertension also adds hypernatremia for SAME, but most sources don't -couldn't find any sources that mention hypochloremia Liddle: -neither hypernatremia or hypochloremia were mentioned anywhere as metabolic findings in SAME

what does presence of (only) anti-HBsAg in serum indicate

prior vaccination

describe chronic hepatitis B presentation

progression to acute → chronic depends on age: -90% peri-natal - ~50% children - <5% adults -many chronic infections asymptomatic (carriers) -risk of progression to cirrhosis, liver failure, hepatocellular carcinoma (viral DNA integrates into host), & reactivation (acute hepatitis)

Type 2 RTA is also known as what

proximal RTA

describe the three main equations that measure renal function

renal blood flow -the quantity of blood reaches the kidneys -an important measurement based off of this is renal plasma flow -how much filterable liquid reaches the kidney -RPF = (1-Hct)*(RBF) -because you can't filter erythrocytes GFR -the amount of liquid passing through the glomerulus Renal Clearance -how much of each component is removed -filtration fraction

RAAS diagram

review

causes of hypertension in children

review

comparison of normal eye & retinopathy

review

ear anatomy

review

glomerulus structure (EM 2)

review

glomerulus structure (EM)

review

review of acid base physology

review

site of diuretics action

review

parts of the nephron

review uses active, facilitated, & simple diffusion

PCT concentration changes

review (PAH, for example, doesn't accumulate more throughout, it just gets more concentrated because none is resorbed)

An alien with blue hair (an autosomal recessive trait) marries an alien who does not have blue hair. Their first child has blue hair. What is the probability that their next alien child will also have blue hair?

see image

In corn, smooth kernels (K) are dominant to wrinkled kernels (k). A farmer crosses two corn plants that are heterozygous for kernel texture. What are the odds that the offspring will have smooth kernels?

see image

categorize the high-yield nephrotic syndromes by whether they have podocyte effacement, immune complex deposits, or are systemic diseases

see image

which two veins join to form the portal vein

superior mesenteric vein & splenic vein

describe the utility of the urine K+:Cr ratio

used to determine is hypokalemia is due to renal wasting or extra-renal losses

how is Liddle syndrome treated and why

with K+ sparing diuretics that block the ENaC channels to combat their hyperactivity (ex: amiloride or triamterene)

what is the difference between global & segmental glomerular diseases

within the individual glomerulus: -global: the whole glomerulus -segmental: part of the glomerulus