Renal & Urology Flashcards

Question

Regulation of Na and H20 transport

Answer 1

-Na (along w/ HCO2 and Cl) and H20 reabsorption are increased by renal nerve activity and angiotensin II-ATII stimulates more NHE, and renal nerves stimulate more NHE and Na/K ATPase-Increasing GFR also increases H20 reabsorption by increasing the oncotic pressure in the capillaries-Na/H20 reabsorption are decreased by DA, (produced in PT during high salt intake and high BP) by reducing NHE and Na/K ATPase

Answer 2

-Phenomenon when solute concentration in tubular fluid exceeds the reabsorptive capacity (Tmax)-This leads to an elevated tubular oncotic pressure, leading to a decreased GFR and small percentage of glomerular filtrate reabsorbed-Most common culprit is glc (diabetes)-Glc remains in PT and increases its oncotic pressure leading to less fluid reabsorption-This increases urine flow, but decreases ECF volume leading to thrust and polydipsia

Answer 3

-Bladder formed from allantois (endoderm of hind gut)

Answer 4

-Mesodermal component of urogenital (UG) septum is derived from intermediate mesoderm-Mesonephros (nesonephric ducts, tubules, and glomeruli) is derived from the mesoderm (not endoderm)-Mesonephros regresses eventually, but before this there is budding of the metanephros which will be the mature kidneys

Answer 5

-From their original sacral position they ascend to their final lumbar position to reside in their retroperitoneal position-Adrenal glands do not ascend with kidneys but form once kidneys are ascended-Fetal urine elimination: the UG membrane breaks down and allows continuity btwn the amniotic fluid and urinary system-Waste is transported to the amniotic fluid and then taken up by placenta

Answer 6

-Paramesonephric ducts are parallel to mesonephric ducts-In males: paramesonephric ducts regress entirely and the gonads are formed from the mesonephros (the rest of the mesonephros regresses)-In females: the paramesonephric ducts are maintained and become the fallopian tubes-The mesonephric ducts regress, but before this part of them become the ovaries

Answer 7

-Males: phallus extends to form pernis, UG folds fuse along the ventral midline to enclose the penile urethra-Labiosacral swellings fuse to form scrotum-Females: phallus becomes clitoris, UG folds remain unfused and become labia minora, labiosacral swelling remain unfused to be the labia majora

Answer 8

-Na is the primary determinant of ECF-Plasma volume increases with no change in osmolality when Na levels increase since H20 is reabsorbed accordingly-Excess dietary salt: increase in ECF, plasma volume, BP, and leads to HTN-Interstitial loss of NaCl and H20 from ECF leads to decreased plasma volume, BP, and leads to shock

Answer 9

-As Na from diet is raised there is a 3 day lag in which Na output t expand b/c it can store Na non osmotically on negatively charged matrix molecules in skin and/or move it into muscle in exchange for K

Answer 10

-Decreased ECF volume: decreased CV stretch (in great veins and atria) increases SNS output to kidneys and causes renin release activating RAAS-Decreased ECF volume also leads to diminished renal perfusion pressure stimulating infrarenal arterial baroreceptoors in the afferent arteriole (myogenic), which stimulates RAAS-Last thing to stimulate RAAS: macula densa (MD) sensing low NaCl transport-Increasing ECF volume increases atria stretch and ANP release to vasodilate and cause diuresis

Answer 11

-Is activates when Na and/or volume is low, and responds by increasing Na reabsorption (all along the nephron) to increase ECF-RAAS also increases vascular contractility thru ATII to increase BP

Answer 12

-Consists of MD (late TAL cells), and juxtaglomerular cells (specialized afferent arteriolar SMCs that make and store renin in granules)-Renin is released in response to increased cAMP (set off by input from MD or SNS) or decrease in cell Ca (set off by less volume/stretch)-Ca inhibits release of renin

Answer 13

-Myogenic: decrease mean arterial pressure sensed by baroreceptors in afferent arteriole leads to a decrease in Ca and thus causes renin release-When there is increased BP/stretch in the afferent arteriole there is an increase in Ca and renin release is inhibited-Decrease in NaCl transport by NKCC in macula densa: chemical signals are transmitted from MD to afferent arteriole (signals: PGs and NO) to stimulate AC, increase cAMP and release renin

Answer 14

-Neurogenic: decrease in extrarenal baroreceptor firing leads to increase SNS to afferent arteriole to stimulate cAMP production and renin release-Metabolic: high levels of glc sensed in MD cells leads to increase in renin release-Hormonal: ATII via AT1 raises Ca levels and inhibits renin release (negative feedback)-Likewise: ANP activates GC to raise cGMP inhibits renin release

Answer 15

-Very rapid effects via AC stimulation or phosphatidylinositol (PI) turnover-Renal Na and H20 retention: increases Na transporter abundance and activity along the nephron (NHE, NKCC, NCC, ENaC)-Increases aldosterone production/release-Aldosterone increases NaCl reabsorption and K/H+ secretion in distal tubule (NCC) and collecting duct (ENaC)

Answer 16

-ATII causes systemic vasoconstriction of arterioles-Regulates GFR by preferentially constricting efferent arterioles and mesangial cells to keep GFR up despite low RBF-Central role: stimulates thirst, ADH release, NaCl appetite

Answer 17

-Can occur to only affect Na reabsorption in one part of the nephron (i.e. proximal tubule)-Will not effect systemic vasoconstriction-Activated during renal injury-Good target to Rx HTN (ACEIs)

Answer 18

-Release stimulated by AGII, high plasma [K], ACTH, and inhibited by ANP-Released from (and synthesized in) adrenal gland (zona glomerulosa)-Is a steroid (mineralcorticoid), thus binds to mineralcorticoid receptor (MR), which moves to nucleus to affect gene expression-It rapidly stimulates synthesis of a S/T kinase Sgk, which increases apical ENaC by decreasing their degradation and increasing their activity, increases Na/K ATPase activity, and increases NCC activity (all rapid)

Answer 19

-Aldosterone also stimulates production of proteins which have delayed effects: increases ENaC and Na/K ATPase-These effects occur in distal tubule and collecting duct (thus increase Na reabsorption in these location)-Note: anything that increases Na reabsorption thru ENaC increases the driving force for K and H+ secretion in the collecting duct, thus aldosterone causes K and H+ secretion

Answer 20

-The mineralcorticoid receptor, MR, can be bound to by other mineralcorticoids and glucocorticoids (cortisol)-Since glucocorticoids are 1000X higher levels than mineral corticoids, there must be a mechanism to inactive the glucocorticoids so the MR is not saturated by them-The nz 11-B hydroxysteroid dehydrogenase (11BOHSD) metabolizes glucocorticoids (cortisol) into inactive forms (cortisone) to prevent saturation and ensure aldosterone can bind

Answer 21

-Stimulates thirst (ATII) and Na hunger (same nucleus)-Renin->ATII also increases NaCl reabsorption in proximal tubule, distal tubule and collecting duct, and stimulates aldosterone release-Aldosterone increases NaCl reabsorption in distal tubule and collecting duct-ATII stimulates ADH, which also increase NaCl reabsorption-Decreased ANP leads to inhibition of ANP effects-SNS activity increases leading to NaCl reabsorption all along the nephron and increases renin release-Overal there is decreased NaCl excretion

Answer 22

-Released when there is excess ECF, made in atria and stored in granules-Release in response to increased atrial stretch, which increases Ca and leads to fusion of granules w/ cytoplasm (ANP released into blood)-When ANP binds to inner medullary collecting duct (IMCD) cells it increases cGMP and inhibits NaCl reabsorption-It also decreases renin release (which decreases ATII, ADH, and aldo)-It increases GFR by dilating the afferent arteriole-Causes systemic vasodilation (increased cGMP leads to decreased cellular Ca) to decrease BP

Answer 23

-Locally produced analog of ANP synthesized in distal tubule-Acts locally via cGMP to inhibit NaCl reabsorption locally in the IMCD-Will not have extra renal effects

Answer 24

-Sensor is increased atrial pressure-Leads to decreased SNS activity to kidneys, decreased renin (thus lower ADH, aldo, ATII), and increased ANP-Overall there is decreased NaCl reabsorption in PT, DT, and collecting ducts-Elevated ANP increases GFR-Leads to increased NaCl excretion

Answer 25

-Occurs in HF, b/c there is lower renal perfusion leading to increased Na retention (from ATII, ADH, aldo, SNS)-Na/H20 retention causes edema, increased atrial stretch and increased ECF-Leads to ANP release to correct the problem-But ANP can't do this b/c ANP mostly works in IMCD, where as the other compounds (ATII, aldo) work at more proximal parts of the nephron so their effects predominate over ANP-This is b/c the Na/H20 is reabsorbed before the IMCD, so ANP can't prevent its reabsorption in the IMCD-Constitutively high levels of ANP lead to desensitization of ANP and ANP resistance (will have high levels of ANP in HF)

Answer 26

-Filtrate should be RBC free and protein free-Plasma proteins are negatively charged, and the glomerular barrier (endothelial cell surface and basement membrane) are both negatively charged-This, along w/ size selectivity from BM and podocytes leads to exclusion of proteins from the ultra filtrate-GFR should be 120ml/min, which is 20% of plasma (80% continues in blood thru peritubular capillaries)

Answer 27

-Size selectivity from BM and podocytes -Charge selectivity from endothelial surface, BM, and podocyte surface-There is greatly reduced filtration of large negatively charged particles (plasma proteins)-Cationic and neutral particles are completely dependent on size, smaller ones are preferentially filtered

Answer 28

-Glomerulus resides btwn two arterioles (afferent and efferent), thus the pressure difference btwn these arterioles is negligible -This keeps hydrostatic pressure high in the glomerulus to drive filtration-Filtration pressure is the sum of hydrostatic pressure of capillaries (constant throughout capillary bed) and bowman's space (constant), and bowman's space oncotic pressure and capillary oncotic pressure (lower near afferent side, higher near efferent side)

Answer 29

-This means that the only factor changing is the capillary oncotic pressure, which increases as you move from afferent -> efferent since there is a higher concentration of albumin (losing fluid but maintaining protein)-This pressure antagonizes filtration, thus more filtration occurs early in the capillary bed than later

Answer 30

-The pressure is relatively constant in these capillaries, to allow for somewhat constant blood flow and adequate reabsorption-2/3 of filtrate reabsorbed in PT

Answer 31

-Glomerular capillary pressure (function of afferent and efferent arteriole resistance): constricting afferent arterioles lead to decrease in RBF and GFR-Constricting efferent arterioles leads to increase/maintains GFR but reduces RBF-Glomerular capillary filtration coefficient (Kf): represents the area and permeability of the glomerulus, can be changed by contraction of mesangial cells (SNS or ATII)-Capillary oncotic pressure can change from changes in protein synthesis

Answer 32

-SNS activity and ATII have the same effects -They both increase Ra and Re (constrict both arterioles), and decrease Kf (contraction of mesangial cells)-ATII constricts both but favors constriction of the efferent arteriole

Answer 33

-Ra is factor under most control, it will determine RBF and GFR-Myogenic mechanisms and tubuloglomerular feedback (TGF) are the primary control mechanisms

Answer 34

-Intrinsic property of SMCs to contract when stretched-When there is increased perfusion pressure of the afferent arteriole (increased stretch) the arteriole will constrict to normalize flow rate and maintain GFR-When perfusion pressure drops the arteriole will relax to maintain GFR

Answer 35

-Juxtaglomerular apparatus (JGA) links the distal TAL w/ the glomerular vascular pole-Macula densa cells (MDCs) located at the JGA sense the transport of NaCl by NKCC and NHE from the filtrate to the ISF-The overall goal is to keep NaCl and volume delivery to the distal nephron relatively constant for fine tuning in the collecting ducts-If NaCl delivery is above normal the JGA will send signals (adenosine) to constrict the afferent arteriole to reduce GFR and normalize NaCl flow to MDCs (also contracts mesangial cells)

Answer 36

-If NaCl transport is below normal (as in decreased ECF) TGF will dilate the afferent arteriole to allow for more GFR and NaCl to MDCs -This is usually over-rode by ATII which will constrict the afferent arteriole, but mostly constricts efferent arteriole-Additionally, when NaCl transport is low, MDCs will send signals to the afferent arteriole cells to increase production and release of renin-RAAS is activated which will try to correct the ECF volume/BP (elevate it) by increasing Na reabsorption along the nephron-TGF only affects afferent arteriole-Overall: high NaCl leads to afferent and mesangial contraction to normalize GFR-Low NaCl leads to afferent and mesangial relaxation and renin release (ATII constricts mostly efferent)

Answer 37

-Increasing arterial BP leads to a decrease of NaCl reabsorption in PT leading to more NaCl in MCDs and TGF to stimulate reduction in RBF and GFR (bad for long term HTN when you want to have higher GFR to clear more fluid from the body)-Increased GFR leads to more NaCl (more filtration) at MDCs, TGF will decrease GFR-Anything that decreases NaCl reabsorption in PT or TAL will increase NaCl deliver to MDCs and leads to TGF reducing GFR-Exception: loop diuretics will prevent NaCl reabsorption but will not stimulate TGF b/c they block the NKCC so the MDCs cannot sense the increase in Na

Answer 38

-Besides detecting NaCl thru NKCC/NHE, the MDCs may also sense volume flow thru deflecting of cilia on apical surface-Cell swelling can also be detected, since NaCl entry is faster than NaCl exit-Communication w/ MDCs and afferent arterioles is thru ATP and adenosine release, which causes SMC contraction to decrease RBF and normalize GFR

Answer 39

-RAAS: stimulated due to baroreceptors, myogenic, and TGF -Constricts arterioles everywhere to keep BP up-ATII will preferentially constrict efferent arteriole to maintain GFR while RBF is reduced (but will also constrict afferent arteriole)-Stimulates thirst, salt appetite, vasopressin release to restore ECF volume-ATII and aldosterone stimulates NaCl reabsorption along nephron to increase ECF volume

Answer 40

-Stimulated by baroreceptors, leads to constriction of arterioles everywhere and increase HR to keep BP up-Increases renin release (RAAS effects)

Answer 41

-Intrarenal baroreceptors sense the low BP and promotes relaxation of the afferent arterioles to increase RBF and GFR (afferent arteriole relaxation may be overruled by ATII vasoconstriction effect)-There is a decrease in Ca to cause the relaxation, and this decrease in Ca causes renin release to activate RAAS

Answer 42

-Decreased NaCl delivery to MDCs turns off the TGF effect, but this is unlikely to matter since ATII will constrict the afferent arteriole

Answer 43

-Glomerulus and proximal tubule are both in the cortex-Loop of henle (descending, thin ascending and thick ascending) in medulla-Macula densa, distal tubule and cortical collecting tubule in the cortex-Medullary connecting tubule and collecting duct in medulla

Answer 44

-Bowman's capsule + glomerulus, glomerulus supplied by capillaries that are btwn afferent and efferent arteriole-Proximal convoluted tubule extends from glomerulus to eventually become LOH-LOH terminates at the MD and then tubule becomes distal tubule, which turns into collecting system

Answer 45

-Renal arteries-> interlobar arteries (btwn pyramids)-> arcuate arteries (perpendicular to pyramids)-Arcuate arteries give off cortico-radial arteries which travel parallel to a pyramid on both sides to feed the two pyramids adjacent to it-Cortico-radial arteries give off afferent arterioles which form capillary beds in the glom and blood exits thru efferent arterioles-Efferent arterioles become peritubular capillaries of the cortex and the vasa recta

Answer 46

-Glomerular capillaries only for filtration, O2 and nutrients supplied by cortico-radial arteries and vasa recta-90% of nephrons are mostly in the cortex, so they are supplied by cortico-radial arteries for nutrients-But juxtamedullary nephrons (those w/ glomeruli near the medullar/cortical junction) are supplied by vasa recta-Some of the LOH and collecting systems in normal nephrons are also supplied by vasa recta

Answer 47

-Glomerular capillaries is high pressure (btwn two arterioles) and vasa recta is low pressure-Ascending vasa recta has fenestrated capillaries, descending vasa recta is continuous capillaries-Vasa recta helps establish counter current exchange system

Answer 48

-Proximal tubule: reabsorption-LOH: thin segment permeable to Na and H2O, thick (TAL) pumps Na but impermeable to H2O (counter current system)-Distal tubule: pumps Na, responds to aldo-Collecting tubules: H20 permeable (responds to ADH), Na pumps (respond to aldo)

Answer 49

-3 layers, from in to out (direction of fluid flow):-Endothelial layer, not continuous, excludes based on charge-Basal lamina layer, continuous, excludes based on charge and size-Podocyte spaces/slit diaphragm: spaces btwn the feet of podocytes (visceral layer of bowman's capsule) filled in w/ protein nephrin-Nephrin over laps w/ other nephrin molecules to create a sieve, filters based on size

Answer 50

-Located in cortex-Afferent arteriole most important for controlling resistance-3 layers to filtration/glomerulus, the last being the podocyte/slit diaphragm

Answer 51

-Longest part of nephron, contains a brush border and microvilli for endocytotic mechanisms-Tight junctions present btwn epithelial cells that can be changed to alter permeability-Basal surface infoldings, baso-lateral membrane w/ abundant Na/K ATPase activity (lots of mito)-Capillaries (fenestrated) very close to epithelia-Capillary hydrostatic pressure low, oncotic pressure high (albumin) to facilitate reabsorption

Answer 52

-Establishes and maintains counter current system: Na reabsorbed from TAL (thick ascending) enters ISF btwn the two limbs (ascending and descending)-The Na gradient in the ISF stimulates H2O reabsorption from the descending limb-Na also reabsorbed in descending limb, but mainly TAL-TAL is impermeable to H2O to maintain this system-Descending limb: no active transport (freely permeable to H20 and Na)-TAL: not permeable, but does actively transport Na across membrane-TAL is "diluting segment" since the osmolality is lowest form pumping out Na and keeping H2O

Answer 53

-Structurally identical to LOH, but different in that it is permeable to H2O (still actively pumps Na)-Main action site of aldo and ADH-Aldosterone will stimulate Na reabsorption-ADH will stimulate H2O reabsorption (by increasing AQP)

Answer 54

-Dominant cell is principal/light cells-These cells have a single motile cilium on luminal surface and are responsible for NaCl reabsorption and adjustments of H2O reabsorption-Dark cells/intercalated cells are also found and specialize in acid-base balance by using H+ transporters-Main jobs of collecting tubules: conducts urine into calyces, modifies urine to final adjustments in Na and H2O retention

Answer 55

-The central cilium is present on the luminal surface of all cells lining the nephron (except intercalated cells)-They have a sensory role detecting tubular fluid flow-Defects are associated w/ cystic kidney disease

Answer 56

-ADH will stimulate H2O reabsorption, but it needs an osmotic gradient to do this-The Na osmotic gradient in the medullar interstitium established by the LOH is the osmotic force behind H2O retention-Since this gradient is always present, the amount of H2O reabsorption depends on the permeability of the collecting tubule to H2O-ADH increase AQPII on the membranes of principal cells thus making the collecting tubules more permeable to water and increasing H2O reabsorption-Aldosterone acts mostly on cortical collecting tubules to stimulate Na pumping and Na reabsorption

Answer 57

-Juxtaglomerular cells are modified SMCs within the media of the afferent arteriole that secrete renin (store in granules)-Macula densa: cell plaque at the end of the TAL associated w/ the JG cells (final portion of TAL located btwn afferent and efferent arterioles)-MDCs detect NaCl movement thru the apical membrane (using NKCC) to modify renin release from JG cells-When NKCC activity is low (not enough NaCl making it to the MD- indicating a low NaCl in plasma and low ECF) the MD stimulates JG cells to release renin to increase NaCl/H2O reabsorption and increase ECF

Answer 58

-MD has very thin or absent BM and these cells face toward the JG cells to facilitate communication-JG apparatus: JG cells + MD cells + lacis cells-Mesangial cells are present within the corpuscle and the arterioles before and after it (lacis cells)-Lacis cells are mesangial cells in the arterioles just outside the glomerulus-They are important b/c they form gap junctions w/ JG cells and allow communication btwn MD and JG cells

Answer 59

-Mesangial cells (those w/in the glomerulus) can be derived from monocytes and can clear debris and turn over matrix w/in the renal barrier-Mesangial cells can also be derived from SMCs (abundant at vascular pole) and provide structural support for glomerular capillaries-Mesangial cells can contract to decrease or maintain GFR (usually coupled w/ contraction of afferent arteriole), and this is usually in response to high NaCl thru the MDCs-Their contraction reduces the surface area of the glomerulus thus lowering GFR (coupled to constriction of afferent arteriole)

Answer 60

-After being absorbed in GI, K is sequestered into muscle to prevent plasma [K] from going up too much-Muscle will release k when levels are low-There is a narrow range of [k] for ECF (3.5-5 mM)-When there is hypokalemia the membranes hyper polarize (larger K gradient-> more leaves the cell)-When there is hyperkalemia the membranes depolarize (less gradient -> more K is retained in cell)

Answer 61

-Na/K ATPase allows for K accumulation in the cell-K channels continuously leak K into ECF-Insulin stimulate K uptake into cells (mostly muscle) by increasing the ATPase activity (this is preserved even in T2 diabetes)-Catecholamines: during exercise there can be transient hyperkalemia as the K effluxes from muscle, so the muscles must reuptake the ECF K. Catecholamines increase ATPase activity to do this (muscles also eventually lose less K with exercise training)-Tissue breakdown releases K into ECF which will need to be cleared by muscle or kidney

Answer 62

-During hypokalemia there is a shift in K from ICF to ECF, by decreasing the ATPase activity (same amount leaving, but less coming in) and by reducing K secretion in the distal nephron (reduced number of ROMK)-Also during hypokalemia the colon reduces fecal K by absorbing more and the nephron reabsorbs more K by increasing H/K ATPase activity-During hyperkalemia (tissue breakdown, injury), the kidneys secrete more and reabsorb less K-Colon increases fecal K by absorbing less, and the muscle will increase the ATPase activity to sequester more

Answer 63

-Since both are positive ions they will compete for negative charges within the cell and displace each other-This means at high levels of one the other will be displaced and its levels will subsequently rise-Acidosis and hyperkalemia are often seen simultaneously (but it depends on acute or chronic acidosis, as chronic can lead to hypokalemia), and alkalosis and hypokalemia are often simultaneous

Answer 64

-In PT: there is reabsorption of 2/3rds of filtered K (mech not clear), but reabsorption of K is proportional to reabsorption of Na in PT (opposite is true in cortical collecting duct)-LOH: 20% of filtered K is reabsorbed by NKCC-CCD (and DT) is where K regulation occurs, as it can change K excretion via either reabsorbing K in CCD or secreting K in CCD (usually secretion unless hypokalemic)

Answer 65

-On a normal K diet, 20% of the filtered load is excreted thus there is net secretion in CCD-On a K rich diet up to 80% of filtered load is excreted, thus there is an increase in net secretion in CCD-On a low K diet only 1% of filtered load is excreted, so there is net reabsorption in CCD

Answer 66

-Primary site of secretion, via ROMK channels-The K secretion is driven by ENaC sodium reabsorption in multiple ways, and this is influenced by how much Na is reabsorbed before the CCD-The K gradient favors secretion (high [K] inside cell, low [K] in lumen) and the apical membrane is more permeable to K than the basolateral membrane so most of it is secreted-The electrical gradient will help facilitate more K secretion when Na reabsorption increases

Answer 67

-When Na amount in CCD lumen increases more is brought in by ENaC, this depolarizes the cell and increases the electrical gradient favoring K secretion to repolarize the cell-Even when Na levels in lumen are not elevated, the overall electrochemical gradient favors K secretion-During K depletion ROMK channels retract from the apical membrane to decrease K secretion (are not degraded and are ready to be re-inserted)-During high K diet more ROMK channels are inserted to increase K secretion

Answer 68

-Primary site of K reabsorption in CCD-Since the electrochemical gradient favors secretion there must be active reabsorption-Apical H/K ATPase facilitates reabsorption of K for secretion of H -There are flow sensitive channels that are activated to secrete K when Na levels are high in CCD lumen (less Na reabsorbed before CCD)

Answer 69

-During hypokalemia there is a decrease in apical K channels and an increase in H/K ATPase activity leading to increased reabsorption-During hyperkalemia there is increased flow sensitive K channel abundance leading to more secretion-Also during hyperkalemia there is tissue kallekrein secreted from connecting tubule cells to deactivate H/K ATPase

Answer 70

-Increased K in ICF (can be from alkalosis) or decreased K in tubule fluid (TF) increased gradient for secretion-Increased Na in TF increases ENaC activity and thus increases electrochemical (EC) gradient favoring K secretionIncreasing Na delivery to CCD by increasing flow does the same as above

Answer 71

-Increased HCO3- (poorly reabsorbed anion) in TF means a larger EC gradient for K secretion (cell gets depolarized so wants to secrete K to repolarize)-Decreased Cl- in the TF of CCD means there are more poorly reabsorbed anions in the TF and has the same affect as above-All of these factors can lead to hypokalemia due to excess K excretion

Answer 72

-Decreased Na reabsorption by ENaC decreases EC gradient driving K secretion-Therefore ENaC inhibitors can cause hyperkalemia-ENaC inhibitors = K sparing diuretics

Answer 73

-Diuretics that act before collecting ducts (LOH and PT) will increase volume flow to CCD (increases Na delivery)-This leads to more activity of ENaC and increased K/H+ secretion-Therefore these diuretics can cause alkalosis and hypokalemia-Genetic diseases: LOF mutations of NKCC (bartters syndrome) or LOF mutations in NCC of DT (gitelmans) both increase volume flow to CCD and cause hypokalemia and alkalosis by activating ROMK and H ATPase (from ENaC activity, same as above)

Answer 74

-Aldosterone: increases Na/K ATPase and Na transport by ENaC thus leading to hypokalemia and alkalosis-Contraction alkalosis: chronic decrease in ECFV stimulate chronicly high aldo levels causing hypokalemia and alkalosis-K rich meal: high plasma K leads to dephosphorylation of NKCC and decreases Na reabsorption in LOH and increases ENaC activity-This leads to increased secretion of K and there is also net secretion of Na

Answer 75

-During alkalosis H+ leaves ICF as K enters ICF (displaces H+), and since there is an increase in ICF K there is a larger gradient for K secretion and excretion-Therefore alkalosis leads to hypokalemia-During acute acidosis H+ enters ICF as K leaves ICF (H+ displaces K) so there is less gradient for K secretion-Therefore acute acidosis leads to hyperkalemia-During chronic acidosis there is an increase in GFR and thus flow to the distal nephron, leading to increased K excretion-Therefore chronic acidosis leads to hypokalemia

Answer 76

-Insulin and B2 adrenergic receptors induce K uptake by stimulating Na/K ATPase-Exercise can result in hyperkalemia by A1 adrenergic receptor activation leading to increased K efflux (this is offset by the B2 activation)-Aldo: lowers serum K by stimulating K uptake into cells and by stimulating kidneys to excrete K -Increases plasma osmolality causes water to move to ECF, resulting in increase in ICF [K]-The resultant feedback response is an inhibition of Na/K ATPase and this shifts net K movement to efflux, leading to hyperkalemia and normalizing the ICF [K]

Answer 77

-Can be due to acidosis (H+ displaces K in cells)-Diabetic ketoacidosis and BBs lead to inhibition of Na/K ATPase and increases net K efflux-Hemolysis, rhabdomyolysis, tumor lysis all can lead to hyperkalemia

Answer 78

-Alkalosis (H+ leaves the cell, K moves in to take its place)-Insulin and B2 increase Na/K ATPase-Aldosterone also increases Na/K ATPase

Answer 79

-Regulated at the collecting duct (principal cells secrete, intercalated cells reabsorb)-Secretion accounts for most of the K excretion (80% of what is filtered is reabsorbed)-K secretion based on the activity of CCD ENaC (K secretion directly proportional to ENaC reabsorption)-Intercalated cells actively reabsorb K thru apical H/K ATPase (antiporter)

Answer 80

-In order of importance:-Luminal flow rate-Distal Na delivery-Aldo-Extracellular K-Extracellular pH

Answer 81

-Increasing luminal flow rate increases K secretion b/c it decreases the extracellular K and leads to a larger gradient for secretion-Osmotic diuresis, increased GFR, decreased Na reabsorption before CCD, diuretics, bartter/gitelmans syndrome all will increase flow rate and can cause hypokalemia-Decreasing flow rate (low GFR, increased PT Na/H2O reabsorption, obstruction) can decrease K secretion and lead to hyperkalemia

Answer 82

-Block ENaC activity and thus reduce K secretion (and H+ secretion)-Can cause hyperkalemia, possibly acidosis-Amiloride is ex

Answer 83

-Loop and thiazide diuretics cause K wasting and alkalosis-Decreasing Na reabsorption before CCD leads to both increased Na delivery to CCD and increased flow-The increased flow washes out K leading to increased secretion-The increased Na increases ENaC activity and thus more K secretion and H+ secretion

Answer 84

-Aldo increases Na/K ATPase activity and ENaC expression-Both of these together lead to increase in K secretion

Answer 85

-Hemolyzed blood, leukocytosis and thrombocyosis-Due to ischemia from prolonged tourniquet time or exercise of the limb w/ tourniquet-Leads to abnormally increased K

Answer 86

-Increased K intake-Decreased urinary K excretion-K shift from ICF to ECF-Excessive K ingestion will not lead to hyperkalemia unless other contributing factors are present-Chronic hyperkalemia cannot occur unless there is decreased K excretion

Answer 87

-Things that move K from inside the cell to outside-Metabolic acidosis-Hyperglycemia (osmolarity effect)-BBs-Digitalis-Hyperkalemic periodic paralysis (recurrent attacks of muscle weakness lasting over 1 hr)

Answer 88

-Blood transfusions-Overdose of IV KCl-Dietary supplements plus renal failure

Answer 89

-Decreased tubular flow either due to renal failure or low ECFV-Decrease in CCD K secretion rate either due to ENaC block or hypoaldosteronism-ENaC block causes: amiloride, other K sprain diuretics-Hypoaldosteronism: type 4 RTA, NSAIDs, ACEI/ARB, heparin, spironolactone-Type 4 RTA: hyperkalemia that is disproportionate to level of GFR, there is mild CKD, acidosis (but normal urine acidifying ability) and hyporeninemic, hypoaldosteronism-Underlying diseases: DM, SLE, obstruction, etc

Answer 90

-Usually ASx-Muscle weakness-Cardiac arrhythmias-ECG changes: wide QRS, peaked T waves, loss of P waves, short ST int, "sine wave" idioventricular rhythm

Answer 91

-Stabilize membrane excitability: CaCl-Increase K entry to cells (rapid and transient): glc + insulin, B2 agonist (albuterol), NaHCO3-Removal of excess K (slow but definitive): cation exchange resin (kayexylate), diuretics, dialysis-Dietary K restriction

Answer 92

-Do not give in bicarb-containing solutions, chance of precipitation-Administer only when ECG changes (loss of P waves or widening of QRS) in pts taking digitalis (can induce digitalis toxicity)-Can cause tissue necrosis if injected SQ-Can precipitate CaPi in tissue in pts w/ renal failure and hyperphsophatemia

Answer 93

-Can cause intestinal necrosis and severe pain-Most likely when given w/ sorbitol

Answer 94

-Serum K artificially decreases after phlebotomy-Usually due to acute myeloblastic leukemia (blast cells take up the K in the tube)

Answer 95

-Can 3 possible causes-Cellular shift-GI loss-Urinary K wasting

Answer 96

-Alkalosis-Insulin-B2 agonist-Hypokalemic periodic paralysis:-Familial: precipitated by meal or exercise, repetitive episodes of acute profound hypokalemia and paralysis lasting hrs-days-Thyrotoxic: predominantly asians, 20-40yo, mostly male, only w/ thyrotoxicosis which may be ASx

Answer 97

-Due to increased K secretion-2 possibilities: increased tubular flow or increased CCD K secretion-Osmotic diuresis increases tubular flow and thus increases K secretion-Decreased PT, TAL, DT Na reabsorption leads to increased K secretion -Increased delivery of Na w/ nonreabsorbable anion to CCD increases K secretion-Hyperaldosteronism leads to increased K secretion-Increased membrane permeability-All of these can cause metabolic alkalosis

Answer 98

-Due to inactivating mutations in transporters of the TAL-Mostly NKCC, but also K channels and Cl channels-Leads to increased Na delivery/flow to CCD and thus hypokalemia/alkalosis

Answer 99

-Due to inactivating mutation in the NaCl cotransporter (NCC) in DT-Leads to increased Na delivery/flow to CCD and thus hypokalemia/alkalosis

Answer 100

-HCO3-, ketoanions delivery to CCD will increase K secretion (associated w/ decreased Cl delivery to CCD)-May be due to vomiting, loss of H+-Amphotericin can increase membrane permeability to K

Answer 101

-Can be due to activating mutations of ENaC (liddle's)-Can be due to high levels of transcribed/translated Aldo (GRA: glucocorticoid remediable aldosteronism)-Can be due to LOF mutation of B-hydroxysteroid dehydrogenase, leading to excessive stimulation of Aldo receptor by cortisol, cushings-Can also be due to high renin: renal artery stenosis, reninoma

Answer 102

-Usually ASx, muscle weakness, polyuria/polydipsia-Rhabdomyolysis-ECG changes: depressed ST segment, flat T wave, prolonged QT, apparent U wave-Arrhythmias

Answer 103

-Oral KCl supplements-IV KCl-concaminant hypomagnesemia must be corrected-Amiloride or spironolactone useful in pts w/ hyperaldosteronism

Answer 104

-Abnormal total body water generates hyponatremia (too much water) or hypernatremia (too little water)-Regulated by ADH-D/o of Na balance leads to volume contraction (too little Na) or volume expansion (too much Na) and is regulated by RAAS-Hypernatremia almost always due to too little TBW (too much water loss, or not enough water consumption)

Answer 105

-TBW is 60% of body mass for men and 50% body mass for women-2/3rds of TBW in cells-1/3rd of TBW in ECF (25% of this in plasma, 75% in ISF)

Answer 106

-RAAS regulates Na reabsorption in distal tubule (increases it)-RAAS activated due to low ECFV, low renal perfusion-ADH regulates amount of total body water (increases H2O reabsorption), and is activated by small increases in serum osmolality and large decreases in blood volume-Other factors can activate ADH release: emotion, CHF, liver disease, drugs, nausea/vomiting, pain/stress, ATII

Answer 107

-Produced and released by paraventricular and supra ventricular nuclei of the hypothalamus (incl. supraoptic nucleus)-Enters the hypothalamus capillaries to be moved to post pituitary, then enters systemic circulation-ADH uses the osmotic Na gradient set up by TAL to increase H2O reabsorption by increasing AQP expression in CD

Answer 108

-Urine output >3L/day and excess loss of free water-Causes: osmotic (uncontrolled DM, hyperosmolar contrast, osmotic diuretics like manitol, excess electrolytes) and water-genic (psychogenic polydipsia, central diabetes insipidus, nephrogenic diabetes indipidus)

Answer 109

-Very low Na content in urine, lots of excess water excreted-Urine Na is low, but serum Na can be normal or high-Causes can be central or nephrogenic

Answer 110

-Decreased ADH production due to hypothalamic or post pituitary lesion -Will have low ADH levels-Possible causes: surgery, trauma, tumors, CVA, infection, mutations

Answer 111

-Inability of kidney to respond to ADH-Will have high ADH levels-Causes: electrolyte d/o (hypokalemia, hypercalcemia), tubulointerstitial nephropaties (SCD, myeloma, obstructions, Li Rx, acute kidney injury)-Familial mutations can cause it (V2 receptor, AQP2)

Answer 112

-To distinguish btwn causes of water diuresis, deprive pt of water then administer ADH -If psychogenic there is no point in giving ADH, since the body is already overloaded with water that ADH levels are near zero as they should be, leading to a very dilute urine-The body is working fine (i.e. getting rid of the excess water normally since ADH response is appropriately turned off), but the pt is drinking too much water-Psychogenic polydipsia does not cause hypernatremia, but does cause hyponatremia (too much water)

Answer 113

-In central DI, administration of DDAVP will increase urine osm since the kidneys can respond to the DDAVP normally, but the brain is not producing its own ADH (ADH levels are inappropriately low- whats causing the polyuria)-Thus administration of DDAVP will cause water retention as expected and increase Uosm-If nephrogenic DI, the DDAVP will not affect urine osm, since the kidneys cannot respond to the DDAVP properly and will not reabsorb the water (urine remains dilute)-Since kidneys cannot respond to ADH must find alternative way to reabsorb water (thiazides)

Answer 114

-Psychogenic: decrease water consumption-Central DI: give DDAVP plus adequate H2O intake-Nephrogenic: increase proximal water reabsorption by low Na diet and thiazide diuretic plus adequate H2O intake-If osmotic diuresis: remove osmolar load

Answer 115

-Thiazides reduce free water excretion in two ways-They cause mild volume contraction by increasing excretion of Na, which increases H2O reabsorption in PT-They impair urinary dilution by increasing expression of AQP2 in CD

Answer 116

-Serum Na > 145mEq/L-Pathogenesis is water intake less than water excretion: net water loss-Decreased water intake plus water loss stimulates osmoreceptors (increases serum osmolality), results in posterior pituitary ADH release-ADH binds to CD V2 receptors and leads to insertion of AQP2 to increase water reabsorption-This increases urine osm and decreases free water excretion

Answer 117

-This process can be interfered w/ at various stages to cause hypernatremia, it could be renal (osmotic diuresis, DI), or extra renal (GI/sweat)-Central DI prevents ADH release-Nephrogenic DI prevents ADH from binding to V2 and/or inserting AQP2

Answer 118

-As ADH is released due to small increases in serum osm, there is stimulation of thirst-Hypothalamic lesions can prevent the thirst response-Even if thirsty, there may be no access to water which will prevent correcting hypernatremia

Answer 119

-They may be receiving IV hypertonic solutions containing Na w/o adequate H2O administration-This increases Sosm and leads to shift of H2O from ICF to ECF

Answer 120

-As high [Na] in ECF pulls H2O from ICF, cells in the brain begin to shrink b/c they are losing water-There can be rupture of cerebral veins and intracranial hemorrhage leading to neuro damage-There can be lethargy, weakness, seizures, coma, and death

Answer 121

-As the brain shrinks the cells begin to increase intracellular organic osmoles, which increase ICosm -This shifts the water back to ICF to normalize brain volume

Answer 122

-Hx: Sx of thirst, decreased access to water, polyuria/polydipsia, diarrhea, diuretics-Break down Dx based on Urine osm-Either the Uosm is 800 (H2O loss from elsewhere- extra renal problem) + decreased water intake

Answer 123

-Either central or nephrogenic DI, use water restriction + DDAVP to Dx (also ADH levels ?)-Can also be osmotic diuresis (due to glc, urea, mannitol, contrast)

Answer 124

-First calculate TBW: 60% or 50% (man vs women) of Kg body weight-then TBW x (Na - 140)/140-Ex: 42 x (172 - 140)/140 = 9.6 L water deficit-Replace 1/2 free water deficit every 24 hrs plus ongoing losses-Do not decrease Sna more than .5 mEq/L per hour or 8-10 per day to avoid cerebral edema-Ongoing losses: all insensible losses, all vomiting and suction, and 1/2 diarrhea and 1/2 urine output

Answer 125

-Rx underlying cause (water intake less than water loss)-CDI: demopressin-NDI: Na restriction, thiazides, amiloride, desmopressin

Answer 126

-Always intake < output-Decreased water intake secondary to impaired thirst or limited access to water-DI does not normal cause hypernatremia unless water intake is limited-Rapid correction of hypernatremia may induce cerebral edema

Answer 127

-Syndrome of inap. ADH secretion (SI ADH) cause serum osm to be low and Uosm to be high (reabsorbs water, concentrates urine)-DI is opposite, the serum osm is high (or normal) and the Uosm is low (can't reabsorb water- either central or nephrogenic deficit)-Hyponatremia in part due to excess free water intake-Hypernatremia in part due to no free water intake

Answer 128

-Sosm: (2Na) + (BUN/3) + (glc/20)-If it goes above 285 the osmoreceptors will stimulate ADH secretion

Answer 129

-3 different types depending on Sosm-Hyperosmolar (>290 Sosm)-Normal Sosm (pseudohyponatremia)-Hypoosmolar (<275 Sosm)

Answer 130

-Due to serum dilution, Na is not actually low, but there is less of it since the % of water in the serum is low-This occurs when there is hyperproteinemia or hyperlipidemia, which increases the protein or lipid phase of plasma and reduces the amount of water in plasma-Since there is less water there is less Na dissolved in a given volume and the lab reads hyponatremic-But within the portion of water present the concentration of Na is normal

Answer 131

-Sosm is high due to presence of osmotically active solutes (glc, mannitol, ionic contrast) which shifts water from ICF to ECF and dilutes out the Na-With hyperglycemia, water is pulled out of the cell into the ECF and thus serum Na shows a low value-However, the Na amount is not actually low, it is just diluted (still hyponatremia since concentration is low)

Answer 132

-We correct for this by calculating a corrected Sna value (the value that Sna would be if the glc were corrected and the water went back into the cell)This is done by adding 1.6mEq/L to the Sna for every 100mg glc over 100mg/dL

Answer 133

-ADH levels will be high, since the body is trying to reabsorb water and bring down the Sosm

Answer 134

-Water intake is greater than water excretion-Normally this will decrease ADH levels to near zero, but some pts will have abnormally elevated ADH levels, which are contributing to the low Sosm-Psychogenic polydipsia can cause hypoosmolar hyponatremia b/c there is excess water intake-There is low ADH since the body has so much water it doesn't want to reabsorb anymore (appropriately dilute urine)

Answer 135

-Can also be due to inability to excrete free water (inappropriate water retention)-Inappropriately high ADH levels due to:-Decreased effective circulating volume (arterial blood) from CHF or liver failure-Hypovolemia (bleeding, diuresis, vomiting, diarrhea)-Drugs (narcotics)-Pain, nausea, and vomiting

Answer 136

-SIADH (Dx of exclusion) often caused by lung and CNS lesions/tumors can lead to euvolemic hypoosmolar hyponatremia-Impaired urinary diluting ability (renal failure) and nephrotic syndrome-Multifactorial, including hormonal mechanisms

Answer 137

-3 different subset of hypoosmolat hyponatremia: hypovolemic, euvolemic, and hypervolemic-Hypovolemic pts will have dry mucous membranes, skin turgor, other hypovolemia findings-Euvolemic pts will have no findings (no edema, dryness)-Hypervolemic pts will have edema-Within each one there are various causes, but for hypovolemia they can be either extra renal or renal

Answer 138

-There will be elevated ADH levels since there is low ECFV (pt is dehydrated)-Can be due to sweating, vomiting, blood loss, renal causes-If Una is low (kidneys reabsorbing Na like they should be) the problem is extra renal-If Una is high (kidneys excreting Na) the problem is renal, as in diuretics

Answer 139

-Can be due to a number of things:-Polydipsia (will have low ADH, low Uosm)-Hormone problems: pituitary, thryroid, or adrenal insufficiency (leads to high Una, high Uosm)-Or SIADH (requires euvolemic hypoosmolar hyponatremia plus high Una plus high Uosm)-Important note: main factor in determining Uosm is not Na, but is urea

Answer 140

-Durgs-Post op: pain, nausea, narcotics-Ectopic production by tumors (small cell CA of lung)-Pulm disease (pneumonia or TB)-Neuropsychiatric d/o: CVA, neoplasm, psychosis

Answer 141

-There is Na and H2O retention, but more H2O retention than Na retention-This causes dilution of Na so much so to cause hyponatremia-Can either be due to CHF, liver failure, or nephrotic syndrome (proteins being filtered by glom)-These causes will result in a low Una (kidney is reabsorbing Na since it thinks it has low volume due to the underlying disease)-The other cause is renal failure, which presents as a high Una, since the kidney cannot reabsorb Na

Answer 142

-Severe Sx when Sna falls below 120-125-Lethargy-Seizures-Coma/death-Due to decrease in Sosm thus shift of H2O from ECF to ICF and resulting cerebral edema

Answer 143

-Exact same as calculating free water deficit (just switch the numerator) -TBW x (140-Sna/140)

Answer 144

-Rx underlying causes-Water restriction-Hypertonic saline for serious CNS Sx-Furosemide: inhibits urinary concentrating ability, and add NaCl-More specific Rx: based on isotonic, hypertonic, or hypotonic

Answer 145

-Isotonic hyponatremia: no Rx-Hypertonic: Rx cause such as hyperglycemia -Hypovolemic hypoosmolar hyponatremia: give volume (saline, blood)-Hypervolemic hypoosmolarhyponatremia: Rx the liver failure/CHF and limit Na/H2O intake and use furosemide-Euvolemic hyponatremia: Rx underlying cause, restrict free water, and furosemide-No survival benefit for V2 receptor blockers

Answer 146

-Acute and Sx hyponatremia: do not exceed 10mEq/L increase in 1st day to avoid brain shrinkage (H2O moves from inside to outside the cells when serum Na is replenished)-This can lead to osmotic demyelination syndrome-Chronic and ASx: increase by .5 mEq/L per hour-Acuity more important than severity

Answer 147

-Central and extrapontine myelinolysis-Risk factors: excessive rate of correction of serum Na after being hyponatremic-Also: malnutrition, and alcoholism, severe liver disease, hypoxia-Presentation: dysphagia, quadriparesis, locked in syndrome-Can be permanent or fatal

Answer 148

-Hyponatremia is caused by water excess, likely due to increase in ADH and/or water intake-Rate of decrease in serum Na best predictor of Sx-Rapid correction of hyponatremia may induce osmotic demyelination

Answer 149

-Osmolality is regulated by water intave vs excretion (ADH)-ECFV is regulated by varying Na reabsorption (RAAS)-These two are usually active at the same time (decreased Posm increases ADH, and decreased ECFV increases RAAS)-Ex: CHF leads to low perfusion (effective circulating volume) which leads to release of RAAS and ADH (RAAS also stimulates ADH release)-This causes reabsorption of Na and H2O, leading to concentrated urine (increased Uosm) and a reduced urine volume-Also leads to expanded ECF and hyponatremia

Answer 150

-Reflect problems with water intake or ADH regulation-Too much water leads to hyponatremia-> cerebral edema (cells swell)-Too little water leads to hypernatremia-> cerebral constriction (cells shrink)-When plasma ADH is high (fluid restricted) there will be small amounts of concentrated urine-When plasma ADH is low (fluid excess) there will be large amounts of dilute urine

Answer 151

-Usual stimulus is increased Posm (as little as 3 mOsm), which causes osmoreceptors in hypothalamus to send signals to PVN/SON to tell post pituitary to release ADH-ADH release is very sensitive to Posm, but can also be due to changes in blood volume (or effective circulating volume)-When blood volume decreases by 10% the stretch receptors in atria and arterial baroreceptors also trigger ADH release-This can be stimulated by low effective circulating volume (CHF, cirrhosis) even if there isn't a real volume depletion-Important to note that while ADH is more sensitive to Posm, higher levels of ADH are achieved when it is released due to low blood volume-Other factors can stimulate ADH release: pain, stress, etc

Answer 152

-Often ADH and RAAS are regulated in concert to restore lost salt and volume (hemorrhage, sweating, fasting)-ADH stimulates thirst so you drink water, which is critical in order to rectify the osmolality/volume status-ADH binds to 2 different receptors in the kidneys-V2 receptor has high affinity for ADH thus will bind at low ADH levels-This receptor increase cAMP which increases H2O and urea permeability in the CD and Na transport in TAL and DCT

Answer 153

-The gradients of urea and Na in the ISF lead to retention of water to concentrate the urine and dilute the plasma-V1 receptors have low affinity and thus only bind ADH when its levels are high-They are located in arterioles and cause vasoconstriction, since the only times when ADH are high enough to activate them are during blood loss, dehydration, and thus hypotension

Answer 154

-Only high levels of ADH will cause V1 and V2 activation-This usually happens when there is large change in blood volume, w/o a change in osmolality (hemorrhage, cholera)-ADH then causes retention of water via V2 and prevents fall of BP via V1-Small changes of osmolality will not cause ADH release to the degree that is required to activate V1

Answer 155

-In TAL and DCT ADH increases Na reabsorption thru NKCC (TAL) and NCC (DCT), as well as increasing K channels and basolateral Cl channels-ADH activates COX for PG synthesis to counteract and buffer the ADH response-Activates AC to generate cAMP for protein kinases-In the CD epithelia there is an increase in AQP2 channels in the apical membrane-This is b/c the activation of protein kinase which phosphorylate AQP2 in their recycling vesicles, and this phosphorylation allows the channels to interact w/ tropomyosin to destabilize the actin barrier than normally prevents their insertion

Answer 156

-Therefore AQP2 is unregulated in the apical membrane and water reabsorption capacity is increased-Water leaves the basolateral membrane via AQP3/4 which are constitutively expressed -Note: AQP1 (in PT) is not expressed in CD and thus not regulated by ADH-ADH also increases the activity of type 1 urea transporters (UT1) in the IMCD cells by phosphorylating UT1, which allows for more urea transport/recycling increasing the ISF gradient for more water reabsorption and urinary concentration

Answer 157

-When ADH levels are high (blood loss, volume depletion), the V1 receptors in VSMCs stimulate a rise in IC Ca and lead to vasoconstriction-This prevents a fall in BP and preserves perfusion pressure

Answer 158

-Increases in Posm is a strong stimulus for water intake-Profound volume contraction can provoke thirst (ATII acting on SFO- no BBB in this region)-Increased BP can inhibit thirst-Gastric Na loading can stimulate thirst before and increase in Posm-ADH released correlated with (but may not cause) thirst

Answer 159

-Urine can be as concentrated as 1200mOsm or as dilute as 50mOsm-This is done by osmolality gradient established by Na reabsorption in LOH and urea recycling along the nephron-Couple this w/ the AQP profile and there can be great variability in H2O reabsorption -All of this is regulated by ADH-Important to realize that the LOH and CDs share a ISF, so changing the osmolality in the ISF by altering Na reabsorption in LOH will affect H2O reabsorption in the CD

Answer 160

-This is the diluting segment, since Na is pumped out of TAL into the ISF but this segment is impermeable to H2O (and urea)-Therefore the fluid in the tubule after the TAL will be dilute since Na has been removed from it-At the same time as the luminal fluid is diluted, the ISF is concentrated -TAL uses NKCC to do this, thus there are many apical K channels to allow for K recycling-ADH increases NKCC and thus increases the gradient

Answer 161

-W/o ADH H2O and urea permeability in distal nephron (DT, CCD, IMCD are low due to retraction of AQP2 and UT1 from the apical membrane-These regions can continue to reabsorb Na w/o H2O to further dilute the urine-Even though there is an osmotic gradient favoring water reabsorption, no reabsorption occurs if the cells aren't permeable to water-Cannot extract all of the salt from the urine (need to excrete some salt to excrete water)

Answer 162

-ADH increases water and urea permeability in distal nephron (up regulates AQP2 and UT1)-Normally the distal neprhon is not permeable to these two-But when upregulated by ADH, the increased permeability for H2O allows the osmotic gradient of the ISF around the distal nephron to pull water back out of the lumen and into the blood-Urea recycling helps this, because reabsorbing urea form the IMCD will increase the ISF osmolality and help pull water from the distal nephron (urea is recycled to LOH)

Answer 163

-When ADH is stimulated and H2O/urea permeability in distal nephron are increased, H2O is allowed to leave the lumen more proximal than urea (H2O can leave after TAL, urea not until IMCD)-As the H2O leaves the luminal fluids [urea] increases, so that once the fluid reaches the IMCD there is a large gradient favoring reabsorption of urea-Urea enters the ISF and then is secreted into the thin ascending (mostly) and descending limbs of LOH, as well as some being carried away by vasa recta (all down the concentration gradient)

Answer 164

-In descending limb there is progressive increase in [NaCl] since there is reabsorption of H2O via AQP1 into the surrounding hypertonic ISF, low permeability to NaCl (concentrating segment)-A little bit of urea secretion-In thin ascending limb: there is passive NaCl reabsorption and secretion of urea all the time-In TAL: active reabsorption of NaCl w/o water reabsorption or urea secretion (diluting segment)-The LOH (specifically the descending and TAL) maintains the osm gradient within the nephron that goes from 285 (cortex)-> 1200 (papilla)

Answer 165

-Slow flow and loop arrangement allow equilibration of ISF and blood and prevents medullary osmotic gradient washout-Increasing flow rate dissipates the medullary gradient (reduces ISF osm), and decreasing the rate limits O2 delivery and thus active transport

Answer 166

-In descending loops of vasa recta there is efflux of water (high ISF osm) and influx of solute (reabsorbing salt)-In the ascending vasa recta there is influx of water as the distal tubule begins to reabsorb water and the ISF gradient falls-Simultaneously there is a decrease in solute reabsorption into the vasa recta in the ascending regions-Net effect: more control over vasa recta osmolality

Answer 167

-IMCD cells are in a unique environment where ECF and ICF osmolalities are both high-They have proteins that can increase expression of osmolytes (like sorbitol) to prevent shrinkage of the cell in the hypertonic environment -The cells also have transporters that can bring in other osmotically active molecules to help hold onto the water so the cells do not shrink in the hypertonic ECF-The transporters and sorbitol are synthesized in response to hypertonicity of the ECF

Answer 168

-Urine is isoosmotic when Uosm is equal to Posm-If urine is dilute, plasma becomes more concentrated (Uosms ability to concentrate urine and dilute ECF)-CH2O: clearance of free water, reciprocal to Cosm (ability of kidney to dilute urine and concentrate ECF)-Cosm = (Uosm x V)/Posm-CH2O = V - Cosm (positive if urine is dilute, negative if its concentrated)

Answer 169

-Increased Posm leads to increased ADH release and thus increase in H2O reabsorption-There is excretion of small amount of concentrated urine, and return of free water to plasma leading to decrease in Posm-When Posm is low there is reduced ADH release, leading to decreased H2O reabsorption and excretion of large amounts of dilute urine-This is excreting lots of free water thus Posm goes up

Answer 170

-Diuretics: causes increase in urine output-Natriuretic: increases Na and water excretion-Aquaretic: increases free water excretion-Most diuretics are natriuretics

Answer 171

-Reduces ECFV (edematous states, HTN)-Adjust ECF K, pH, or Ca

Answer 172

-PT: osmotic diuretics, carbonic anhydrase inhibitors (CAIs)-TAL: loop diuretics-DT: thiazide diuretics-CCD: K-sparing diuretics

Answer 173

-Work at the PT where HCO3 is reabsorbed-Ex: acetazolamide-If CA is blocked there is less CO2 being brought into the cell and thus less H+ formation-As the H+ gradient is depleted there is reduced Na reabsorption thru NHE

Answer 174

-This causes natriuresis, but can also cause bicarbonaturia and metabolic acidosis-Since there is more Na moved to the CCD there is increased K secretion and thus can lead to hypokalemia-There is TGF and distal compensation which limits their effectiveness

Answer 175

-All of these inhibit Na reabsorption proximal to the CCD-Increasing Na deliver to CCD increases K and H+ secretion by increasing Na reabsorption in the CCD (ENaC)-Therefore its possible to see hypokalemia and metabolic alkalosis with these diuretics-However its more common to see metabolic acidosis w/ CAIs

Answer 176

-Since there is more NaCl flowing to MD there will be TGF-Vasoconstriction of the afferent arteriole will decrease GFR-There is RAAS activation-ATII will further constrict the efferent arteriole preferentially to maintain GFR but decrease RBF-This limits the effectiveness of CAI diuresis

Answer 177

-Inhibits NKCC in the TAL and MD-This is also the region where Ca and Mg reabsorption occurs (based on activity of NKCC and ROMK in setting up electrical gradient)-Thus inhibiting NKCC will decrease Ca and Mg reabsorption-Inhibiting Na reabsorption here also increases reabsorption of Na in CCD thru ENaC, and can lead to metabolic alkalosis and hypokalemia-There is no TGF response since the NKCC channels are blocked

Answer 178

-There is impaired urinary diluting and concentrating ability since the TAL is responsible for the Na reabsorption that establishes the gradient allowing for adjusting how concentrated or dilute the urine is-They are such a potent diuretic that there is a fall in ECFV and the body responds by activating RAAS and SNS to keep BP/GFR up and increase Na reabsorption in other parts of the nephron-Na reabsorption mostly increased in PT, by activating NHE-Leads to more bicarb reabsorption and furthers metabolic alkalosis

Answer 179

-Almost all diuretics must be secreted into the lumen to have an effect (90% not filtered)-The exception is an osmotic agent (they are filtered straight into the lumen)-All other diuretics use organic acid secretion to enter the lumen and have an effect (most PT)-Spironolactone works from peritubular circulation

Answer 180

-Work in the DT by blocking NCC (Na Cl cotransporter)-The DT is a urine diluting site (Na permeable but H2O impermeable)-B/c of this, reducing Na reabsorption here can cause a drop in serum [Na] (won't happen in areas where H2O reabsorption occur concomitantly b/c as Na reabsorption falls so will H2O) and cause hyponatremia

Answer 181

-These are weak diuretics but are synergistic w/ loop diuretics-Can cause hypokalemia and metabolic acidosis (increased Na to CCD)-There is decreased Ca excretion but increased Mg excretion-Impairs diluting ability, but not concentrating ability (concentrating ability relies on TAL)

Answer 182

-Inhibit ENaC activity in the CCD and thus reduce K and H+ secretion-Spironolactone works by blocking the aldosterone receptor (not on ENaC directly- only ones that act intracellularly)-Weak natriuresis, and can cause hyperkalemia and mild metabolic acidosis

Answer 183

-Endogenous: urea, glucose-Exogenous: mannitol, urea-These agents are not reabsorbed but stay in the lumen and thus create an osmotic gradient that pulls water (and Na via drag) back into the lumen-Primarily active in PT, since they inhibit free H2O reabsorption they can cause hypernatremia (lose more H2O than Na)-This is impairing urinary concentrating ability (but not urinary diluting ability)

Answer 184

-A failure of renal compensation, based on hereditary and environmental factors -BP is a function of ECFV and RAAS/SNS-Kidneys have a physiologic role in maintaining pressure natriuresis-Kidneys set the BP for the body by adjusting Na and ECFV

Answer 185

-High arterial pressure signals for NaCl excretion-Increased arterial pressure means less NaCl reabsorption in the PT (as a % of NaCl in PT- there is more of it)-Leads to more NaCl delivery to MD which leads to TGF-TGF will maintain a steady GFR despite this rise in arterial pressure, to bring Na filtration back to normal

Answer 186

-On top of this there is a natriuretic response, which is decreasing Na reabsorption in PT to increase Na and volume excretion -This is done by removing Na channels from the apical membrane of PT cells-This decreases Na reabsorption and normalizes BP by decreasing effective circulating volume

Answer 187

-The long term regulation of BP is to control ECFV above that which is needed to maintain CO/perfusion but below that which will cause damage to CVS/kidneys-Kidneys will control baseline BP by regulating ECFV, which is based on dietary Na intake-A higher level of Na would cause an increase in ECFV, but the kidneys promote Na and H2O excretion to normalize ECFV-However this is at the expense of BP, since the BP baseline will increase as dietary Na increases even though ISF isn't increases-Thus the BP set point is increased w/ increase in Na intake

Answer 188

-HTN is less likely to affect those w/ a low Na/K ratio-HTN depends on low K, not just those w/ high Na intake

Answer 189

-Usually due to a problem w/ increased aldosterone secretion (tumor)-With this example, the increased aldo leads to increased Na reabsorption in the CCD-This will increase the ECFV and BP, so pressure natriuresis will go into effect-The Na reabsorption in PT will decrease and since this is proximal to the site of action of aldo there will be a reduction in the ECFV, leading to a slightly normalized BP-The BP will stay elevated since the baseline Na has been raised (changes BP set point at which Na intake = Na output)-The problem gets corrected everywhere (not just PT, also TAL and DT) except the site of the problem (CCD)

Answer 190

-Na wasting d/o-Gitelmans: LOF mutation in NCC in DT leads to hypotension and accompanying hypokalemia and alkalosis-Bartters: LOF mutations in NKCC, apical K, or basolateral Cl (anything that decreases Na reabsorption in TAL), also leads to hypotension, hypokalemia, and alkalosis-Pseudohypoaldosteronism (PHA): either due to LOF mutation of mineralcorticoid receptor or LOF mutation of ENaC (both lead to hypotension w/ hyperkalemia and acidosis)

Answer 191

-Hyperaldosteronism or pseudohyperaldosteronism (mutations leading to activation of NCC)-LOF mutations of 11BOHSD can lead to pseudohyperaldo (excess licorice consumption will do the same)-Liddles: mutation in ENaC causes prolonged/excessive channel retention and Na reabsorption in CC-MR mutations that allow binding of progesterone (appears during pregnancy)

Answer 192

-Renovascular HTN: renal artery stenosis of a kidney causes RAAS activation from that kidney but leads to unregulated Na reabsorption from both kidneys and increases BP (goldbatt HTN)-Renin-secreting tumor or elevated levels of angiotensinogen-Gordons: mutations in WNK/SPAK leads to constitutive activation of NCC-Calcineurin inhibitors prevent inactivation of NCC

Answer 193

-Increases Na reabsorption thru ENaC in CCD, leads to increase in ECFV and BP-This is detected by increased atrial stretch which decreases SNS activity to kidney and increases ANP synthesis and release-ANP will decrease IMCD Na reabsorption, and decrease RAAS/ADH release-Increased MAP leads to increased renal perfusion pressure and thus decrease in RAAS and stimulation of pressure natriuresis-Together these work by correcting the situation by reducing Na reabsorption everywhere in the nephron except in the CCD (where the problem lies)-BP stays elevated since baseline Na has gone up, but new equilibrium established for Na in = Na out

Answer 194

-Body produces metabolic acidic waste, must excrete about 60mEq/day thru kidneys-2 different functions of tubule acid secretion (same as HCO3- retention)-Reabsorb filtered HCO3- to the blood to buffer -Form new HCO3- in kidney to buffer the blood-Limitation: transporters responsible for acid secretion (NHE and H ATPase) stop working when tubular lumen pH falls below 4.4 (b/c of steep uphill gradient)

Answer 195

-In PT and TAL HCO3- is reabsorbed by being converted to CO2 in lumen by CA (requires a secreted H+), crossing the apical membrane and being converted back into HCO3- by CA inside the cell-The HCO3- is transported across the basolateral membrane by Na-bicarb cotransporter (NBC) which uses the bicarb gradient-In the CD, there is no CA in the lumen (HCO3- to CO2 rxn is much slower), and the transporter that brings HCO3- into the blood on the basolateral membrane is a HCO3-/Cl- anti porter

Answer 196

-For all of this to happen there must be H+ secretion via NHE and H+ ATPase (PT/TAL) or H+ ATPase and H/K ATPase (distal nephron)-Net effect: filtered HCO3- is reabsorbed and returned to circulation but the molecule that is brought over the basolateral membrane is not necessarily the same molecule that is reabsorbed-Inhibiting CA (acetazolamide) or Na/H exchanger (amioride) will inhibit reabsorption of NaHCO3 which reduces isoosmotic H2O reabsorption and leads to diuresis and loss of NaHCO3

Answer 197

-Filtered buffers in the tubular fluid can trap secreted H+ and buffer the fall in lumen pH-Phosphates, sulfates, urate, creatinine can do this-This helps to maximize the amount of new HCO3- formed, by helping to prevent the lumen pH fall below 4.4 when the secretion of H+ is largely halted-This capacity is based on the amount of filtered buffers-More filtered buffers means more bicarb formation (want H+ secretion b/c its required for HCO3- reabsorption and helps facilitate making new bicarb, but too much means pH falls below 4.4 and then H+ secretion stops)

Answer 198

-As blood H+ rises the blood HCO3- falls (becomes CO2), therefore the kidneys try to replenish HCO3- (in two ways)-To do this the lumen must not fall below 4.4 pH (otherwise H+ secretion and thus HCO3- reabsorption and some HCO3- formation stops), which is done in part by filtered buffers to maximize HCO3- reabsorption/formation-Tubular epithelial cells (in PT and DT) will make new bicarb from the excess CO2 in them, this ability is limited by the lumen [buffer] -The CO2 (made in the cell or diffused in from blood) is converted to HCO3- by CA and the HCO3- is brought back over the basolateral membrane to the blood-New HCO3- can also be formed from glutamine (not dependent on filtered [buffer])

Answer 199

-In the mito of PT epithelial cells, glutaminases (activated by fall in pH) metabolize glutamine into NH4+ and aKG-The NH4+ will be secreted NH3 + H+ or NH4+-The aKG is further metabolized to glucose and HCO3- (which is reabsorbed)-This newly formed HCO3- will buffer the fall in blood pH by replacing the lost HCO3-, and its formation is not limited by filtered [buffers] (doesn't form an H+ so doesn't need buffer in lumen)-However, the effective amount of HCO3- created by ammonia genesis corresponds to the amount of NH4+ secreted/excreted

Answer 200

-Formaiton of new HCO3- generated by ammoniagenesis can be consumed in the process of urea production (in liver) if a molecule of NH4+ is reabsorbed with the HCO3-, instead of excreted-In normal individual, 50% of the NH4+ is reabsorbed and 50% excreted-This is good b/c its keeps the formation of HCO3- in balance so alkalosis doesn't occur (half of the created HCO3- is eliminated thru urea production)-But during acidosis we want to minimize this so the HCO3- formation is maximized-This is achieved by increasing the amount of NH4+ excreted

Answer 201

-Important: NH4+ can use any channel/transporter that K can use-NH4+ produced in PT by ammoniagenesis is secreted into the lumen via NHE and K channels-It is reabsorbed in the TAL via NKCC -In the ISF it can either be in the form of NH4+ or NH3 (depends on pH)-The [NH4+] in ISF is high in the distal nephron due to the reabsorption at the LOH

Answer 202

-NH4+ is thus secreted back into distal nephron lumen thru an NH4+ transporter-Chronic acidosis increases this transporter activity and abundance in the apical membrane to maximize NH4+ excretion and thus HCO3- formation-There will be some NH3 in the ISF in the region of the CD, and this must be excreted in order to maximize HCO3- formation

Answer 203

-To excrete NH3, it must first be secreted (passive diffusion down gradient) into the lumen of the CD, where is must be trapped (converted to NH4+) to remain there and be excreted-This process of trapping NH3 depends on the amount of H+ secreted by the CD intercalated cells (H+ ATPase)-During metabolic acidosis H+ secretion increases which traps more NH3 and thus increases NH4+ excretion-In the end, urinary NH4+ is a measure of new HCO3- formation during metabolic acidosis

Answer 204

-Durin chronic metabolic alkalosis, the kidneys produce an alkaline urine to acidify the bodily fluids-This is done by intercalated cells in CD which flip their polarity-Meaning, the H+ ATPase is on the basolateral membrane (instead of apical) and the Cl/HCO3- anti porter (pendrin) is on the apical (instead of basolateral) membrane-This results in a cell that secretes HCO3- and reabsorbs H+, both actions bring the pH down to normal

Answer 205

-RAAS activation stimulates aldo activity-Aldo increases Na reabsorption (in part) thru ENaC, which increases H+ and K+ secretion-Thus RAAS can lead to hypokalemia and alkalosis

Answer 206

-Reciprocal relationship btwn cell [H+] and [K+]-During hyperkalemia the H+ is displaced from the cell so less is secreted, also meaning less HCO3- is reabsorbed-Hyperkalemia also decreases NH4+ excretion (leads to acidosis) in 2 ways-K+ competes w/ NH4+ for transporters, thus more K+ secreted and less NH4+ secreted-And since K+ displaces H+ from ICF, a reduction of H+ secretion means less NH3 is trapped, more NH3 reabsorbed and less HCO3- formed to buffer pH drop-Thus hyperkalemia can cause metabolic acidosis

Answer 207

-But metabolic acidosis can cause hyperkalemia by displacing K+ from cells and reducing its secretion (also opposite of the above happening), thus leading to hyperkalemia-Hypokalemia can lead to alkalosis (more H+ enters cells as K+ levels fall and thus more H+ secreted)-Similarly, alkalosis can lead to hypokalemia because as H+ levels drop more K+ enters cell and is secreted (less H+ being secreted b/c want to bring pH up, meaning there is less NH4+ competing w/ K for transporters thus more K secretion)

Answer 208

-As GFR increases more HCO3- is reabsorbed in PT since the [HCO3-] at end of PT must be constant (deliver more = reabsorb more)-As ECFV decreases there is release of ATII (RAAS) leading to increased NHE in PT (increases H+ secretion and thus HCO3- reabsorption)-There is also more ENaC activity in CCD (aldo) leading to increased H+ and K+ secretion-PCO2 determines [HCO3-] in all cells, so when CO2 increases during respiratory acidosis, the kidneys compensate by increasing H+ secretion and HCO3- reabsorption

Answer 209

-Must note: H+ secretion is based on HCO3- reabsorption (85% of H+ secretion due to HCO3- reabsorption)-Thus when there is less HCO3- reabsorbed there is less H+ secreted-HCO3- reabsorption goes down in metabolic acidosis since there is less HCO3- in blood and thus less filtered-Therefore, during metabolic acidosis H+ secretion actually goes down (due to less HCO3- reabsorption)-But this drop in H+ secretion is partly countered by all of the mechanisms above (the body wants to secrete more H+ so it tries to do so)-The opposite is true for alkalosis: H+ secretion goes up (b/c of high HCO3- filtration/reabsorption) even though the body wants to decrease H+ secretion-Therefore the body implements the mechanisms above to increase H+ secretion

Answer 210

-Decrease in HCO3- is metabolic acidosis-Increase in PCO2 is respiratory acidosis-Increase in HCO3- is metabolic alkalosis-Decrease in PCO2 is respiratory alkalosis

Answer 211

-Metabolic acidosis (decrease in HCO3-) is compensated by respiratory alkalosis (decrease in PCO2 means increasing RR, so you get hyperventilated in met acidosis)-Likewise, respiratory alkalosis is compensated by metabolic acidosis-Metabolic alkalosis (increase in HCO3-) is compensated by respiratory acidosis (increase in PCO2 means reducing RR, so you get hypoventilation in met alkalosis)-Likewise, respiratory acidosis is compensated by metabolic alkalosis

Answer 212

-Compensation is never complete-Respiratory compensation rapid, renal is slow-Compensation may or may not be appropriate degree-Degree is based on how much compensatory change there is per 1 unit change of the primary d/o-If there is appropriate compensation it is a simple d/o-If the compensation is not appropriate the d/o is mixed-Important note: hypoxia will also override a compensation (thus respiratory compensation for metabolic alkalosis is variable b/c can't hypo ventilate too much)

Answer 213

-pH: 7.35-7.45-PO2: 75-105mmHg-PCO2: 33-44mmHg-HCO3-: 22-28 mEq/L

Answer 214

-First look at pH to determine if its acidosis or alkalosis-Then look at bicarb to see if its a compensation of primary disturbance-Then look at PCO2 to see if its compensation or primary disturbance-If pH is low and bicarb is low its metabolic acidosis (PCO2 will be low- compensation)-If pH is high and bicarb is low (compensation) its respiratory alkalosis (PCO2 will be low)

Answer 215

-If pH is high and bicarb is high its metabolic alkalosis (PCO2 will be high-compensation)-If pH is low and bicarb is high (compensation) its respiratory acidosis (PCO2 will be high)-Whatever the compensation is (either changing PCO2 or HCO3-), it is always in the same direction as the primary d/o but the other component is changing

Answer 216

-For each 1 mEq/L drop in HCO3-, there should be a 1.2mmHg drop in PCO2-To do it quickly, compare the PCO2 to the last 2 digits of the pH-These two numbers should be close to each other (≤3)-If they are not then the response is not appropriate-If, for example, the pH is high but both PCO2 and HCO3 are shifted toward alkalemia (PCO2 down and HCO3 up- going in opposite directions) there is no compensation, or it is not appropriate, thus the problem is mixed

Answer 217

-Ingestion of acid: breakdown products of ethylene glycol, methanol, toluene, salicylic acid-Endogenous generation of acid: lactic acidosis, ketoacidosis (from DM or etoh), rhabdomyolysis-Defective acid excretion: renal failure, distal renal tubular acidosis-Loss of alkali: diarrhea, proximal renal tubular acidosis (RTA)

Answer 218

-Represents unmeasured anions - cations difference (mainly due to albumin normally)-Formula: [Na] - ([Cl] + [HCO3])-Normal gap is 8-12-Causes of high anion gap metabolic acidosis: MUDPILES plus rhabdo and toluene-Workup to differentiate btwn DDxs: serum urea, Cr, glc, CK, ketones, lactate, etoh, salicylate, urine microscopy (crystals = toluene)

Answer 219

-DDx for high anion gap-Methanol-Uremia-Diabetic Ketoacidosis-Paraldehyde-Iron and isoniazid-Lactic acidosis-Ethylene glycol and etoh-Salicylates-Also: toluene and rhabdo

Answer 220

-Calculated osmolality: 2[Na] + [BUN]/2.8 + [glc]/18-If this is >10mOsm/kg different from the measured Sosm there is a high osmolal gap-DDx for high anion and osmolal gap metabolic acidosis: ethanol, ethylene glycol, propylene glycol, methanol-High osmolal gap but no anion gap: isopropanol-High anion gap but no osmolal gap: salicylates

Answer 221

-Diarrhea or renal tubular acidosis-Hyperchloremic state b/c lose HCO3- and gain Cl- at equal rate so no gap forms

Answer 222

-Failure of kidneys to excrete acids-RTA is selective defect in tubule acid/bicarb handling-Renal failure is decrease in # of functioning nephrons-3 types of RTA: proximal and (type 2) distal (distal further broken into type 1 and type 4)

Answer 223

-Type 2: can't reabsorb HCO3 in PT, can be due to MM, heavy metals (wilson's) Rx with high levels of NaHCO3-Type 1: distal tubule can't secrete H+ thus can't form NH4+, can be due to autoimmune (SLE, sjogrens), cirrhosis, amphotericin Rx w/ low NaHCO3-Type 4: not enough NH4+ excretion due to hypoaldosteronism-> hyperkalemia (also hyporeninemic), can be from DM, SCD, obstruction Rx w/ low K diet and diuretics

Answer 224

-Urine NH4+ and HCO3- are both high in type 2 and both low in type 1 and 4-Urine pH is >5.5 in type 2 and type 1 (type 1 pH should be higher than type 2) and <5.5 in type 4-Serum K is low in type 2 and 1 and high in type 4

Answer 225

-Ingestion of alkali (antacids, citrated blood)-Loss of acid, GI (vomiting, suction) or renal (diuretics, barter/gitelman, hyperaldo)-Cellular shift: hypokalemia causes increased [H+] in the cell thus more secretion-Increasing NaCl delivery to CCD can cause alkalosis due to increased H+ secretion (diuretics, barter/gitelman)

Answer 226

-If Sx seem to be hyperaldo (hypokalemia, met alkalosis, HTN), but aldo levels are low its cushing's (high cortisol)-If hyperaldo Sx (hypokalemia, met alkalosis, HTN) and aldo levels are high then its either due to renin (renin high) or primary hyperaldo (renin low)-High renin: renal artery stenosis-Low renin: primary hyperaldosteronism (tumor)

Answer 227

-Requires impairment of renal excretion of excess bicarb even if origin of alkalosis was not renal -Reduce renal blood flow can be due to decreased effective circulating volume (vomiting)-Can also be due to renal failure-Failure to excrete HCO3-: either due to proximal tubule increasing Na and HCO3- reabsorption (ATII) or distal tubule is secreting large amounts of H+ (secondary hyperaldo)

Answer 228

-Hyperaldo: volume status is increased, urine Cl is increased (NaCl does not correct alkalosis)-Vomiting: volume status is normal or decreased, urine Cl is decreased (NaCl does not correct alkalosis)-Diuretics abuse/bartters: volume status is normal or decreased, urine Cl is increased (NaCl does correct alkalosis)

Answer 229

-Decline in renal function over hrs to days, mostly by rise in serum Cr and BUN (drop in GFR)-May or may not be associated w/ drop in urine output (oliguira= <100ml per day)-May or may not be associated w/ uremic Sx: anorexia, nausea, vomiting, cramps, restless legs, sleep d/o, mental status change, seizures, fluid/electrolyte disturbances, anemia, platelet dysfxn and pericarditis-Etiologies are pre renal (functional AKI), renal (structural AKI), or postrenal (obstructive AKI)

Answer 230

-Increase in Cr from baseline of at least .3-50% increase of Cr-Urine output <80 for Cr to rise much-AKI can be stage 1, 2, or 3 depending on severity

Answer 231

-Azotemia (high nitrogen): increased BUN and Cr are markers-Hyperkalemia-Metabolic acidosis-Volume overload-Hyperphosphatemia-AKI is reversible but CKD is irreversible

Answer 232

-Prerenal: sudden and severe drop in BP or interruption of RBF-Intrarenal: direct damage to kidneys from inflammation, toxins, drugs, infection, reduced blood supply-Post renal: sudden obstruction of urine flow due to enlarged prostate, kidney stones, tumor, or injury

Answer 233

-Intravascular depletion: diarrhea, vomiting, diuretics, hemorrhage, dehydration-Decreased effective intravascular volume: HF, cirrhosis, sepsis-Renal hypoperfusion: renovascular disease, NSAIDs, ACEIs, hepatorenal syndrome

Answer 234

-Kidneys perceive decreased RBF as depletion of ECFV, thus respond by the following-RAAS/SNS stimulation leading to Na reabsorption and ADH release leading to concentrated urine that is low Na (Una 20)-Usually have oliguria-May show normal urinalysis if caught quick enough (no epithelial cell sluffed off to form casts, just hyaline casts)-Normalization of renal function upon correction of the hypo fusion

Answer 235

-Orthostatic Sx/hypovolemia signs-Tachycardia-Fat neck veins-Volume loss Hx (diarrhea, vomiting, diuretics, hemorrhage)-HF-Liver disease-Hypervolemia signs (edema, JVP, ascites)-Thirst

Answer 236

-Volume repletion-Discontinue the problem (NSAIDs, diuretics, etc)-Cardiac support from inotropes

Answer 237

-Upper tract obstruction (ureter): intrinsic or extrinsic-Intrinsic: kidney stone, transitional cell CA-Extrinsic: retroperitoneal adenopathy, AAA-Lower tract obstruction (bladder neck): BPH (!!! most common), prostate CA, urethral stricture, neurogenic bladder

Answer 238

-Hx: flank pain, hematuria, pelvic malignancy, Sx of bladder outlet obstruction (nocturia, urgency, frequency, decreased stream, incomplete voiding)-PE: distended bladder, enlarged prostate, ab/pelvic mass-Diagnostic studies: ultrasound, CT scan (hydronephrosis from back-up of urine)

Answer 239

-Relief of obstruction-Recovery of renal function is dependent on the duration of the obstruction

Answer 240

-Vascular: atheroembolic (will have systemic emboli w/ petechiae or purpura), malignant HTN-Glomerular: glomerulonephritis (GN)-Tubular: acute tubular injury (ATI)-Interstitial: acute interstitial nephritis (AIN)

Answer 241

-Etiologies: post-strep GN, lupus nephritis, membranoproliferative GN, antiGBM/goodpasture's disease-Presentation: nephritic syndrome-Nephritic syndrome consists of: hematuria (dysmorphic RBCs in urine), RBC casts, proteinura-Dx requires biopsy

Answer 242

-Presentation of ATN: nephrotoxic meds (antibios, IV contrast, NSAIDs), muscle trauma (rhabdo), episodes of hypotension, cardiac arrest, cardiac bypass, sepsis-Urinalysis: Una>40, FeNa >1%, +/- oliguria-Urine sediment shows granular casts (muddy brown granular casts) and tubular epithelial cells-Rx: discontinue drug, supportive Rx

Answer 243

-Triad of: fever, rash, eosinophilia-Urinary findings: pyuria, WBC casts, eosinophiluria, hematuria-Rx: discontinue offending drug, possible steroids

Answer 244

-Severe volume overload (refractory to diuretics)-Severe hyperkalemia-severe met acidosis-Signs and Sx of uremia

Answer 245

-DM-Amyloid-PCKD-HIV-All other CKDs show w/ small kidneys-CKD = kidney damage for over 3 mo

Answer 246

-Only the smallest plasma proteins can get thru the GBM (most are immunoglobins)-Plasma proteins account for 50% of protein excretion in urine, the other 50% are non-plasma proteins such as Tamm-horsfall glycoproteins (constituent of matrix in casts)-Microalbuminuria is urinary albumin btwn 30-300mg/24hrs-The filtered proteins are small (less than 60kD), linear (or round) and flexible, and most are positively charged-Normally, most of the protein that is filtered is reabsorbed

Answer 247

-Luminal membrane of endothelial cells is negatively charged-The GBM contains type 4 collagen (target of Abs in anti-GBM/goodpasture's and mutation target in Alport's syndrome) and other negative charges: heparin sulfate, proteoglycans-Slit diaphragm and podocyte membrane covered by sialoglycoproteins (gives podocytes negative charge)-Loss of sialoglycoproteins (and resulting loss of negative charge of podocytes) can lead to increased protein excretion

Answer 248

-Spaces btwn foot processes that create the slit diaphragm are normally maintained by the repulsion of negative charges-When the charges are lost the foot processes tend to collapse and foot processes are fused together-Loss of negative charges also facilitate the accumulation of immune-complexes in glomerular mesangium (contributes to glomerulosclerosis)

Answer 249

-Due to increased glomerular permeability from loss of negative charges along the GBM or alteration of normal GBM structure-In this proteinuria, albumin is usually the dominant protein in urine (selective proteinuria)-Less frequently there is proteins of higher molecular weight (non-selective proteinuria) -Minimal change disease is more associated w/ selective whereas focal and segmental glomerulosclerosis tends to be non-selective

Answer 250

-Renal cells in PT have a prominent lysosomal system responsible for reabsorption of proteins that pass thru the GBM-Thus diseases that affect tubular functions (falcon syndrome, analgesic nephropathy) may result in decreased reabsorption and proteinuria-Characterized by increased excretion of low MW proteins

Answer 251

-Due to excessive production and filtration of proteins across the GBM-Increased urinary excretion of proteins of low MW and size-Ex: hemoglobinuria, myoglobinuria, monoclonal light chains (MM pts)

Answer 252

-Constant: occurs both during day and night-Orthostatic: occurs only during the day but not at rest-Transient: typically concurrent with an acute illness and will resolve upon resolution of the illness

Answer 253

-Sx of the syndrome: proteinuria >3.5gm/day, hypoalbuminemia, edema-Other possible Sx: hyperlipidemia, Ca disturbances, hypercoagulability, thyroid dysfxn-Hypoalbuminemia is due to the loss of negative charges in the GBM (selective proteinuria)-There is renal loss of protein, along w/ tubular degradation leading to further protein loss-Hepatic synthesis of albumin increases to compensate for hypoalbuminemia-Occasionally other larger proteins (IgG) can be lost too (non-selective)

Answer 254

-2 hypothesis: underfilling and overfilling-Hypoalbuminemia may cause a decrease in effective arterial blood volume which stimulate neural hormonal factors to reabsorb Na and H2O (for the 1/3rd of pts that have hypovolemia)-In overfilling (2/3rds of pts have hypervolemia), the cause of renal Na retention is unknown (thought to be due to proteinuria), but its not due to RAAS b/c renin and aldo levels are normal and ACEIs do not prevent the Na reabsorption

Answer 255

-Metabolic derangements: alteration of Ca and vit D, reduced IgA and IgG (increased IgM), increased susceptibility to infection, malnutrition-Hyperlipidemia: increase in all non-HDL lipoproteins (HDL normal), with increase in LDL/HDL ratio (increased LDL synthesis, reduced catabolism)-Hypercoagulability can often cause renal vein thrombosis or PR-Hypercoagulability usually due to decreased AT/APC/APS or factor 5 leiden mutation

Answer 256

-Most are idiopathic, but many are secondary to diabetic nephropathy, amyloidosis, SLE, neoplasia, drugs, infection-Idiopathic forms based on histology: minimal change disease, membranous glomerulonephritis, focal and segmental glomerulosclerosis, membranoproliferative glomerulonephritis, IgA nephropathy

Answer 257

-Nephrotic syndrome has a larger degree of protein urea (usually >3.5g/day), little if any hematuria, and show oval fat bodies (Maltese cross)-Nephritic syndrome has less proteinuria if any (usually <3.5g/day), more hematuria, and RBC casts-For nephritic syndrome, check if there is normal or low complement levels

Answer 258

-A count of >3 RBC/HPF (high power field) is positive for hematuria-Looks brown-red, coffee colored-Transient hematuria is common and in younger pts is usually benign-In older pts transient hematuria may indicate malignancy-Hematuria may occur after physical activity-Could be from contamination by menstrual blood-Not all red urine is hematuria, first check dipstick to see if RBCs are present

Answer 259

-Neoplasms of bladder, ureter, or prostate-Stones anywhere-UTI, prostatitis-BPH -Hemorrhagic cystitis (cyclophosphamide) or radiation cystitis-Catheter-Anticoag

Answer 260

-Can be glomerular or non-glomerular-Non-glomerular: tumors, SCD, renal vein thrombosis, hypercalcemia, renal malformations (PCKD, medullary sponge kidney), infection, drugs, trauma-Glomerular: isolated or nephritic syndrome-Isolated causes are either IgA or inherited diseases (thin basement membrane for women, Alport's syndrome in men-X linked)-Nephritic syndrome consists of: hematuria, proteinuria not nephrotic range), reduced renal function, HTN-Causes of nephritic syndrome include SLE nephritis, post-infectious GN, IgA, anti-GBM/goodpasture's, membranoproliferative GN

Answer 261

-Benign familial hematuria mostly affecting women-Mutations in type 4 collagen alpha chain 4-Only Sx is hematuria

Answer 262

-X linked thus mostly affecting males-Mutations in type 4 collagen alpha chains 3, 4, and 5-Associated w/ deafness, proteinuria and HTN-Progresses to ESRD

Answer 263

-Low serum complement (complement depleted): SLE, post-infectious GN, membranoproliferative GN (MPGN)-Normal serum complement: IgA, anti-GBM/goodpasture's

Answer 264

-May be glomerular or extra-glomerular-Glomerular hematuria usually presents w/ brown/red urine and often a more severe proteinuria (>500 mg/day)-There are dysmorphic RBCs (bleb and RBC casts-In extraglomerular hematuria the urine is red or pink, proteinuria is less severe (<500 mg/day)-There are usually no dysmorphic RBCs or RBC casts

Answer 265

-Smoking, exposure to chemicals/dyes-Hx of gross hematuria-Old age (>40)-Analgesic abuse-Pelvic radiation-Cyclophosphamide use

Answer 266

-Intravenous pyelogram (IVP), ultrasound, CT scan-Renal biopsy indicated if findings suggest intrinsic renal disease (positive urine sediment, proteinuria) and factors associated w/ poor prognosis (proteinuria >1g/day, elevated Cr)

Answer 267

-Focal: 50% of glom involved-Segmental: lesions affecting just a portion of the glom-Global: lesions affecting the entire glom-Sclerosis: increased amounts of basement membrane (GBM), mesangial matrix and collagen (leads to obliteration of glom)-Crescent: macs, fibroblasts, epithelial cells aggregated in bowman's space

Answer 268

-Collection of signs/Sx including edema, hypoalbuminemia, hypercholesterolemia, proteinuria (usual >3.5g/day)-There is structural and/or charge barrier loss of GBM (fusion of podocyte foot processes)-Pathologic features: obliteration and fusion of podocyte foot processes, changes in microvilli swelling of epithelial cells, protein reabsorption (hyaline) droplets in PT epithelial cells-Lipid w/in tubular epithelial cells and peritubular macrophages, these are sloughed off as oval fat bodies seen in urine sed (Maltese cross- tells you its nephrotic syndrome but not what kind)-Primary: issue is in the glom-Secondary: glomerular injury is a feature of multi-organ disease

Answer 269

-Primary nephrotic syndrome w/ few or no glom abnormalities by light microscope but epithelial foot process obliteration by EM (only abnormality)-Most common in children, incidence usually 2-3, but can occur in young adults-MCD is primary (problem is in the glom), but it can be secondary to drugs (NSAIDs, penicillin), toxins (metals), infection, tumors (hodgkin lymphoma)-Acute onset, usually after viral URTI, usually w/ heavy proteinuria, edema, and oval fat bodies (OFBs)-GFR often normal, steroids should correct the problem (if not-> FSGS)

Answer 270

-Thought that dysfxn of T cell immunity leads to production of a cytokine that induces podocyte damage, loss of foot processes and sialoproteins (loss of - charge)-Under LM there is no abnormal findings-EM shows loss of foot processes-Lipid droplets intracellular and interstitium of PT epithelia (desquamate as OFBs) and protein reabsorption droplets in PT lumen (granular hyaline appearance)

Answer 271

-Primary nephrotic syndrome that is rare in kids and most common in black adults-Sclerosis of some glomeruli (focal) in which a portion of the glom (segmental) is affected-Pts have heavy non-selective proteinuria and can be associated w/ microscopic hematuria, reduced GFR and HTN-May be idiopathic or secondary to: HIV, heroin, SCD, unilateral renal agenesis, obesity, HTN, reflux nephropathy-Often will progress to ESRD, will recur in Tx pts, may or may not respond to steroids

Answer 272

-Renal biopsy is required for Dx, but since it is focal and segmental the sample size is very important-Lesions initially affect the juxtamedullary glomeruli-Thought that a permeability factor produced by a rogue lymphocyte clone damages the podocytes leading to injury and depletion-Genetic mutations (APOL1 gene) in podocyte structural proteins can causes FSGS

Answer 273

-HTN or loss of renal mass can produce glomerular hyper filtration and podocyte stress, leading to damage-In LM, there is segmental collapse of the glom w/ exudative lesions (hyalinosis) and foam cells w/in the sclerosis from entrapment of large molecules in the scarred areas-These lesions are positive for IgM and C3-EM shows capillary collapse, sub endothelial and mesangial e- dense deposits and loss of foot processes

Answer 274

-Severe proteinuria, rapid loss of renal function and not responsive to steroids (most blacks), does recur after Tx-Segmental or global glom collapse w/ proliferation and hypertrophy of podocytes-Can be primary or secondary to viral infection (HIV, parvo, CMV)-Podocytes are infected by the virus or are damaged from cytokines released due to infection-Podocytes become dedifferentiated and dysregulated-APOL1 allelic variants (blacks) have increased resistance to infection but a greater risk of developing FSGS

Answer 275

-Primary nephrotic syndrome characterized by diffuse thickening of capillary walls of glom, produced by sub epithelial (btwn podocyte and GBM) immune deposits and associated GBM rxn-Most frequent cause of nephrotic syndrome world-wide, can be idiopathic or secondary to systemic disease (MG signs/Sx may proceed manifestation of disease by months)

Answer 276

-Diseases that can cause MG: immunologic d/o (SLE, RA), neoplasms (non-hodgkin lymphoma), infections (hep B/C), drugs (NSAIDs) -Clinical findings: nephrotic syndrome, mostly normal urine function, HTN uncommon, +/- renal vein thrombosis-Can respond to steroids

Answer 277

-Diffuse uniformly thickened basement membranes (subepithelial deposits under BM) with thickening of capillary walls-Silver stains show spikes protruding from the external surface of capillary walls w/ domes btwn spikes (spike dome appearance)-Granular deposits of IgG and C3, w/ primary MG displaying mostly IgG4/IgG3 and secondary MG has all IgG subsets-EM shows e- dense deposits (immune complexes) in the subepithelial area-Thickening of GBM due to deposits and from podocytes over producing BM material (forms the spikes)-These changes also result in loss of podocyte foot processes and microvillous changes

Answer 278

-The in situ immune complexes can be due to 2 mechanisms-A local (intrinsic) Ag is released from podocytes in primary MG (Ag is PLAR) and is deposited in the GBM on the sub epithelial side-IgG and C3 then pass thru the GBM (IgM can't pass thru GBM) and bind to the PLAR resulting in immune complex deposition-In secondary MG there is an extrinsic Ag that is planted in the subepithelial GBM location, based on its charge and size-Then circulating IgG penetrate the GBM and complex w/ it (Ag is often from hep B)

Answer 279

-A secondary nephrotic syndrome of sclerosed gloms/tubules secondary to thickened mesangial matrix and GBM, and arteriolar narrowing (hyaline arteriolosclerosis due to non enzymatic glycosylation of vascular BM)-Process scars tubules b/c the BM gets so thick it cuts off blood supply to tubules, also increasing efferent artery pressure (selectively thickens efferent artery) will increase GFR and thus cause hyperfiltration and damage (ACEIs help prevent this)-Clinical features: proteinuria, HTN, retinopathy-Most frequent cause of ESRD in US

Answer 280

-Biochemical abnormalities of BM: increased glc, galactose, glycosylations, increased collagen, fibronectin-Hemodynamic factors: early in course there is increased GFR (hyperglycemia-> reduced mesangial contraction) leading to glomerular sclerosis and protein deposits-Looks like MG but no immune depositions, often shows kimmelstiel wilson nodules from sclerosis of mesangium-Early changes show mild thickening of GBM w/ increase in mesangial matrix 2-8 yrs after onset of diabetes-Pathognomonic: hyaline deposits in both afferent and efferent arterioles (!)-Generalized tubular BM thickening, lamina densa can be 6-10x thicker than normal

Answer 281

-Proteinuira, HTN and renal insufficiency-Nodular mesangial matrix accumulations (kimmelstiel-wilson nodules) result from repeated damage to mesangial cells and augmented synthesis of mesangial matrix in response-Is seen in diabetic pts and diabetic glomerulosclerosis

Answer 282

-Secondary nephrotic syndrome, often w/ HTN, +/- renal vein thrombosis -Often adults 40-50, Dx by rectal, fat pad, or renal biopsy (renal biopsy not done usually b/c there can be bleeding since amyloid prevents contraction of arterioles)-Theres glom, vascular, and interstitial amyloid deposition-Mesangial cells (only phagocytic cell) consumes the amyloid (first accumulates in the mesangial cell)-After saturating mesangial cells, the amyloid extends into sub endothelial space and BM where it may disrupt the charge and structural barrier

Answer 283

-There are mesangial and sub endothelial fibrils measuring 8-10nm (small) and form a meshwork-Dx by congo red stain w/ apple-green birefringence-Usually from polymerized Ig light chains (AL: amyloid light chain) but can also be from serum protein (AA: amyloid associated) which is an acute phase protein in response to infection (TB) or inflammation (RA, osteomyelitis)-Dialysis associated amyloid: B2 microglobulin

Answer 284

FSGSAssociated w/ APOL1 allelic variants

Answer 285

-Inflammatory d/o involving the glom primarily and affecting other renal structures secondarily-There are either circulating immune complexes or in situ immune complex formation/deposition-Immune complexes cause glomerular damage mainly by activating complement and enlisting inflammatory cells-Some nephritic syndromes do not activate complement and therefore have normal complement levels (not complement depleted)

Answer 286

-Normal complement nephritic syndromes: IgA, anti-GBM/goodpasture's-Low complement (depleted): post-infectious GN, SLE GN, membranoproliferative GN-The mesangium attempt to eradicate the immune complexes by phagocytosing them, leading to mesangial cell hyperplasia and increased ECM

Answer 287

-The sub endothelial area (btwn endothelium and GBM, continuous w/ mesangium) begins to acquire deposits and extracts inflammatory cells from the blood-The sub epithelial area sees accumulation of deposits since Ags released from epithelial cells (podocytes) are trapped by the GBM and held until circulating Abs complex with it-Ags of LMW (and cationic) can also work their way thru the BM to be planted in the subepithelial area where circulating Abs complex with the Ags

Answer 288

-Pathognomonic findings: dysmorphic RBCs, RBC casts, hematuria-Other findings: acute onset, poor renal function (AKI), proteinuria (may or may not be nephrotic range), HTN, complement may be low or normal

Answer 289

-Most common in kids (5-15), usually due to URTI of strep (may be staph, other bacterial, viruses, parasites)-Important to know onset of renal Sx after infection, b/c thats how to differentiate it from IgA-Onset of renal Sx about 2 weeks after infection (IgA is a few days), Sx include hematuria, HTN, oliguria, edema-Urine sediment shows RBCs, red cell casts, leukocyte casts, and proteinuria (usually <2g)

Answer 290

-Serum complement (C3) is low, usually positive anti-step O (ASO)-Sx usually self-limiting w/in a few weeks and usually no substantial sequelae in children-In adults the progression is more variable and may continue to ESRD, particularly if there are abundant crescents (structures in bowman's space due to break in GBM, glomerulus is done)

Answer 291

-Gloms show diffuse hypercellularity caused by influx of PMNs and macs into capillary lumens w/ swelling of endothelial cells-Crescents may occur in Bowman's space (worse prognosis)-EM shows sub epithelial humps along GBM: dome-shaped e- dense deposits that protrude from the outer surface of the BM into the urinary space-There are less conspicuous mesangial and sub endothelial deposits-The deposits are positive for IgG and C3 and present a lumpy-bumpy or granular pattern (granular = immune complex deposits), later in the disease C3 is the dominant deposit

Answer 292

-PSGN is an immune-complex disease of bacterial Ags and host Abs complexes (both circulating and in situ- at both sub epithelial and sub endothelial levels) that activate complement-The Strep Ag is usually an exotoxin (SPEB), which is cationic and can cross the GBM-Important to note that it is the sub endothelial, not sub epithelial, complexes that stimulate the immune response (sub epithelial complexes are sequestered behind the GBM and thus do not attract inflammatory cells- as seen in MGN)

Answer 293

-Glomerular nephritis due to circulating (and some in situ) immune complexes secondary to SLE-Pts often have concomitant SLE findings: malar rash, photosensitivity, arthralgias, serositis, chronic fatigue-Other Sx include hematuria and/or proteinuria (often nephrotic range), pts may have elevated ANA and/or anti-dsDNA and show low complement levels

Answer 294

-Process of immune complex findings, first in mesangial cells then in sub endothelial area then in sub epithelial area (starts as focal- class 3- then progresses to diffuse- class 4)-There are Igs of all types (IgG, IgA, IgM) and many complement components -e- dense deposits spread out from mesangium to sub endo to sub epithelial-Tubulo-reticular structures (TRS) can be seen, which represent proliferation of SER in endothelial cells and lymphocytes, secondary to a high interferon level

Answer 295

-The circulating immune complexes penetrate the fenestrated endothelium but cannot get past the GBM-They are shunted to the periphery where mesangial cells phagocytose them (also other leukocytes that influx to the region) producing hypercellularity-Once this system is overwhelmed the complexes are deposited in the sub endothelial area of the GBM and complement readily binds and attracts PMNs causing the GN (initially affects some glomeruli-focal- but eventually affects most glomeruli- diffuse)

Answer 296

-Glomerular staining of IgA in the absence of SLE-Disease is similar to SLE in pathology by much more chronic and low-grade-Onset is important, as the nephropathy is either syngenic w/ the URTI or just a few (2-3) days after the infection-Males affected more than females-Pt presents w/ hematuria and a URTI (or GI infection) still ongoing or recent

Answer 297

-There is often mild proteinuria (nephrotic syndrome uncommon), serum IgA elevated and IgA deposits can also be seen in dermal vessels-Normal complement levels b/c the disease is so chronic and slow that complement is not depleted-Progression is chronic and variable, and it infrequently causes loss of Tx kidney (takes too long for damage to occur)-Associated w/ henoch-schonlein purpura

Answer 298

-HSP is characterized by skin purpura (LE and butt), arthralgias, ab pain (vasculitis or GN)-Is a more systemic and severe IgA disease-Same lesions as IgAN but more severe GN-Usually presents in young children and is often transient

Answer 299

-LM findings range from little change to mesangial matrix and cell expansion either diffusely or locally (similar to SLE)-Predominant IgA (+/- IgM/IgG) and C3-EM shows mesangial deposits w/ or w/o sub endothelial e- deposits (immune complexes)-Progression of deposition: mesangial regions-> hypercellularity/matrix-> sub endothelial regions (focal-> diffuse)

Answer 300

-Pts can present w/ nephrotic and/or nephritic syndromes-MPGN I is a morphologic pattern resulted from immune complex deposition in which all or nearly all glomeruli show mesangial cell proliferation and thickening of the BM-This usually affects older children and young adults (7-30) and is usually preceded by an URTI (or hep C/B)-Most pts have low C3 levels, and half of pts will develop CKD

Answer 301

-Thickened capillary walls and hyper cellular glomeruli-There is peripheral extension of the mesangial cytoplasm inter positioning onto the BM (mesangial cytoplasm btwn endothelium and BM)-New BM is made internal to the old BM, leading a tram-track (double contour, causes a lobulated look of the glom-reduplicated) look (silver stain)-E- dense deposits (C3 and IgG) are present as granular patters in mesangial cells and sub endothelial areas-The Ag that stimulates the immune complexes is unknown, but autoimmune disease and chronic infection are known to cause complex formation

Answer 302

-Capillary wall thickening and mesangial cell proliferation associated w/ presence of worm-like dense deposits in BM-Rare compared to MPGN I, same age range but differs in that most pts have persistent hypocomplementemia (low C3-C9 but normal C1q, C4 as opposed to type I which C1q/C4 are low when there is low complement)

Answer 303

-There is thickening of BM and hyper cellular glomeruli-BM are thickened by ribbon-like eosinophilic bands-Pathognomonic findings: elongated, sausage-like e- deposits w/in the lamina dense of GBM and BM of bowman's capsule/tubules (+/- in mesangial cells)-NO staining for Igs or C1q/C4-Thought to be due to systemic dysregulaiton of alternative complement pathway resulting in persistent complement activation and glomerular deposition of C3

Answer 304

-May be due to unregulated activation of C3 convertase causing rampant activation of alternative pathway-Will have C3NeF, which is an autoAb that stabilizes C3 convertase-Could also be due to deficiencies in Factor H and I, which promote decay of C3 convertase thus lacking H and I would cause activation of alternative pathway

Answer 305

-Most aggressive nephritis, characterized by pulmonary hemorrhage and crescentic GN due to circulating anti-GBM Ab (goodpastures is anti-GBM disease w/ lung involvement)-Incidence mostly 30-50 range, young men and older women-1/3rd of pts have isolated renal crescentic GN, flu like syndrome may be a prodrome

Answer 306

-Classic syndrome: pulmonary hemorrhage (manifested by alveolar infiltrates, hemoptysis, and anemia), rapid onset of oliguria, increasing serum BUN/Cr and rapidly progressing renal failure-Some have proteinuria, nephrosis is unusual-Pts have nephritic sediment, serum complement is normal-IgG deposited along the glomeruli (and sometimes tubule) BMs

Answer 307

-A form of GN in which the majority of glomeruli contain accumulations of cells w/in bowman's space-These are monocytes from blood, epithelial cells, and fibroblasts-Crescentic GN is always associated w/ fibrin in Bowman's space and usually w/ breaks in the GBM-It is the pathologic finding in pts w/ "rapidly progressive GN" (RPGN) which is rapid renal failure

Answer 308

-Macs derived from blood and proliferated podocytes seen w/in bowman's capsule-There may be segmental fibrinoid necrosis there and some PMNs, but no endocapillary proliferation or mesangial hypertrophy-There is staining of the BM (glomerular and +/- tubular) for IgG and sometimes C3-The fibrin in the bowman's capsule acts as an irritant causing an influx of macrophages and creating the crescent

Answer 309

-There is a very fine linear pattern of Ig deposition w/in the basement membrane-Pathogenesis is an autoimmune disease in which an Ab to alpha-3 chain of type IV collagen develops and binds to BMs, fixing complement and causing the inflammatory response-Environmental factors (smoking, viral infections) have been linked to is, as have some genetic factors (HLA DR, DQ Ags)

Answer 310

-AIN is an autoimmune inflammatory reaction characterized by interstitial edema and infiltration of inflammatory cells (T cells, plasma cells, eos)-Manifestations range from ASx to AKI, most common features seen are fever, rash, arthralgias, eosinophils in urine-The "classic triad" is fever, rash, urine eos-This is a hypersensitivity reaction (usually to penicillins/cephalosporins/sulfonamides/NSAIDs), but it leaves the glomeruli and renal vasculature normal-Signs of AIN include oliguria -Una >20 and FeNa >2% (renal cause; can't reabsorb Na)-Urinalysis: RBCs, WBCs, WBC casts, urine eos, some protein

Answer 311

-Can cause a variety of AKIs, including AIN (w/ or w/o nephrotic syndrome)-AKI due to NSAIDs blocking COX and leading to a decease in PGE causing vasoconstriction-While this can cause an AIN, it is not the same as typical hypersensitivity AIN (not the same Sx/signs)-These pts may have nephrotic syndrome most likely due to minimal change from T cell dysfxn-Most forms of drug-induced AIN are self-limiting once the offending drug is discontinued

Answer 312

-Caused by many things, mostly aminoglycosides (gentamycin), IV contrast, ampotericin-Characterized by tubular epithelial cell necrosis showing RBC, muddy brown granular casts and tubular epithelial cell casts in urine sed-Pts present w/ uremic Sx: weakness/fatigue, nausea/vomiting, metabolic acidosis, mental changes

Answer 313

-One of the most common forms of ATN, usually occurs 7-10 days after Rx and produces AKI w/ normal urine output-Rx is supportive w/ discontinuation of the aminoglycoside-Prophylaxis: adequate fluids, avoid simultaneous use of other nephrotoxins, use lowest dose, monitor, adjust according to renal function

Answer 314

-In part tubular injury is due to fee radical generation and fall in renal perfusion (due to endothelia release)-Incidence is negligible in pts w/ normal renal function but increases for those w/ impaired renal function-Risk factors: old age, renal problems, DM, CHF, cirrhosis, high dose-ATN will usually appear 24-48 hrs after the administration of contrast (normal urine output)-Recovery is one week-Prevention: .9% NS will expand plasma volume to prevent this

Answer 315

-In amphotericin ATN there is a dose-dependent decline in GFR w/ oliguria or anuria-Can lead to hypokalemia and hypomagnesemia-Can be prevented by NS-Nephrogenic systemic fibrosis (NSF): pts develop large areas of hardened skin w/ fibrotic nodules and plaques-NSF due to someone w/ renal failure is given gadolinium contrast-Analgesic abuse nephritis (AAN): main culprit is phenacetin (maybe aspirin, acetaminophen) and causes a chronic interstitial nephritis due to decreased renal bloodflow

Answer 316

-Decreased RBF leads to: decreased GFR, azotemia (elevated Cr, BUN), and oliguria (typical AKI findings)-There's reabsorption of fluid (RAAS active) since there is decreased kidney blood flow-BUN will always follow the direction of bulk flow, thus BUN reabsorption is also increased-This leads to a serum BUN:Cr >15 (normal is 15)-Since tubular function is intact the FeNa will be low (500)

Answer 317

-Due to obstruction after kidneys, leads to back pressure which reduces GFR and causes other AKI findings-Early stages: like pre-renal AKI, there is overall reabsorption of water and thus BUN in tubules (tubules are intact)-Therefore in early stages the FeNa will be 500 and BUN:Cr >15-Late stages: like ATN, there is eventually damage to the renal tubule epithelia and therefore decreased reabsorption of H2O, BUN, Na-Leads to inability to concentrate urine (Uosm 2% and BUN:Cr <15

Answer 318

-Due to LOF of tubule epithelial cells, there is BUN:Cr 2%, and Uosm <500-Elevated BUN and Cr-Hyperkalemia (decreased K secretion) w/ anion gap metabolic acidosis (decreased H+ secretion)-Ischemic ATN is often preceded by pre renal AKI-Toxic ATN: aminoglycosides, heavy metals, myoglobinuria, ethylene glycol (also forms CaOx crystals), radiocontrast, urate (tumor lysis syndrome)

Answer 319

-Inflammation of just the interstitium-Often caused by NSAIDs, penicillins, diuretics-Presentation: oliguria w/ fever and rash-Eos in urine-Resolves w/ cessation of drug-May progress to renal papillary necrosis-Renal papillary necrosis: presents w/ gross hematuria and flank pain-Causes of RPN: NSAID abuse (phenacetin, aspirin), DM, SCD, severe acute pyelonephritis

Answer 320

-Characterized by intraparenchymal renal cysts that are lined by single layer of epithelial cells-ADPKD mutations may be in 1 of 2 places, but most of the mutations are on chrom 16p13.3 (APKD1/2)-The gene mutated (polycystin) mediates interaction btwn ECM and cells-Cysts are in medulla and cortex, kidneys are enlarged-Dx of ADPKD is usually made via ultrasound

Answer 321

-First there is local dilation of renal tubule, which expands by proliferation of a monoclonal cell w/ the PKD1 mutation -The epithelial cells then pump fluid into the space creating a cyst and loss of functional renal parenchyma-For this fluid to be pumped into the lumen the cells' polarity must be flipped (NKCC on basolateral side, CFTR and AQP on apical side allowing Cl and H2O to accumulate in the lumen)-There is increased CFTR activity from increased cAMP, which is elevated due to lack of functional PC1-> decreases IC Ca (Ca enters thru PC1)-> increase in IC cAMP-This process of forming a cyst requires 2 hits to PC1

Answer 322

-Sx start in 2nd-3rd decade and usually present w/ flank pain due to hemorrhage, pyelonephritis and hematuria, HTN or renal insufficiency, inability to concentrate urine, renal failure-HTN results from activation of RAAS due to cyst stretching and attenuation of intrarenal vessels-The kidneys are irregular, large, and palpable-Complications include UTI, perinephric abscess, infected cyst, hemorrhage of cyst, renal calculi, and obstruction-Extra renal complications: intracranial aneurysms and cerebrovascular events (berry aneurysms), liver cysts (w/ normal liver fxn but possible ascites), colon diverticular, ao regurg, cysts in pancreas and ovaries, mitral valve prolapse

Answer 323

-A deficiency in a5 (and a3/a4) collagen, X-linked (males) present with hematuria-Most will end up on dialysis/ESRD-Tx recipients may develop anti-GBM since their body is not accustomed to having an a5 antigen, thus they will make Abs against the new kidney's BM-Alport's associated w/ deafness, and blindness/lens abnormalities

Answer 324

-Thin BM is mutation in collagen a4 resulting in diffuse attenuation of GBM-Most often in females, only manifestation is hematuria-Alport's syndrome is mutations in a3, a4, a5 collagen that is almost exclusively males (X linked)-Pts present w/ hematuria and can also have deafness and eye problems

Answer 325

-More severe, cyst formation occurs in utero-Infants present w/ worsening renal failure, HTN-May present w/ potters syndrome-Associated w/ congenital hepatic fibrosis and hepatic cyst

Answer 326

-Cysts form in medulla, kidneys are shrunken (not enlarged like in PKD) w/ parenchymal fibrosis

Answer 327

-Abnormalities of renal tubules and interstitium w/ sparing of the glomeruli-May be due to injury, infection, reaction to substances, ischemia

Answer 328

-Inflammation of the kidney and its pelvis, affecting the tubules and interstitium-Pts have costovertebral tenderness-Acute pyelonephritis (APN) is usually associated w/ UTIs (usually E coli/enteric bacteria)-Most common mechanism is ascending infection from bladder, which is promoted by urine stasis (obstructive uropathy, reflux)-Pregnancy increases risk, as does immunosuppression-Diabetes predisposes for UTI: nephrogenic bladder, urine stasis, decrease WBC function, vascular problems

Answer 329

-Lab data: pyuria (pus in urine), WBC casts, organisms in blood-Pathology: grossly the kidney is enlarged w/ yellow streaks and inflamed calyces and pelvis-Microscopically there is infiltration of PMNs into the interstitium and tubules w/ micro-abscesses-There is lots of space btwn tubules, but this space is filled w/ PMNs-Complications: septicemia and shock, preterm labor, papillary necrosis (in DM pts), pyonephrosis (pus obstruction causing hydronephrosis), perinephric abscess

Answer 330

-Chronic tubulointerstitial inflammation and renal scarring w/ involvement of calyces and pelvis-Calyceal involvement (blunting of calyces) distinguishes CNP from other tubulointerstitial diseases-Combination of etiologies, most important being bacterial infection but also reflux and obstruction play a role-There is scarring of the renal parenchyma and distortion of the renal calyces and pelvis (dilation of pelvis and calyces)

Answer 331

-Grossly there is lots of fibrosis, microscopically there is patchy atrophic tubules and surviving tubules that may be hypertrophic and dilated w/ colloid casts (thyroidization- since it looks like thyroid tissue)-There is interstitial fibrosis but the glomeruli are spared initially-Calyces and pelvis develop fibrous thickening and show chronic inflammation (mononuclear cells)-Clinical manifestations: often insidious onset and is not recognized until renal failure-Pt has bacteriuria, pyuria, proteinuria, and elevated BUN/Cr-Can't progress to renal cell CA

Answer 332

-A form of CNP in which there are foamy macs mixed w/ plasma cells, lymphocytes and PMNs w/ occasional giant cells-Associated w/ proteus infections and often superimposed obstruction (calceal stag horn calculi)-Looks similar to renal cell CA, but can't progress to renal cell CA

Answer 333

-Caused by drugs, analgesics, radiation-Drugs includes penicillins, rifampin and cause a hypersensitivity rxn (1 or 4) or have a directly toxic effect -These drugs produce AIN, characterized by abundant eos, PMNs, lymphocytes, macs in interstitium but gloms are normal-Analgesic nephropathy is usually due to excessive use of phenacetin and presents as papillary changes w/ patchy/diffuse necrosis of epithelial cells w/ interstitial fibrosis-Its a chronic interstitial nephritis due to decreased RBF-Radiation nephritis is often from CA Rx and it causes glomerular hyalinization

Answer 334

-The medulla is particularly susceptible to ischemia due to its high O2 consumption-Lack of renal perfusion leads to vasoconstriction and a reduced GFR/oliguria-Most frequently seen after an episode of shock (sepsis, burns, trauma, hemolytic anemias)-If blood flow to kidneys is restored in time the tubules will regenerate (glomeruli/DT normal)-Microscopically there are short segments of focal tubular necrosis at multiple points along the nephron (different necrosis pattern than toxic-induced necrosis)-In ischemic ATN there are parts of the PT affected, but its mostly the thin ascending limb thats affected-Can see brown granular muddy casts in urine sed + Tamm Horsfall protein (granular casts)

Answer 335

-Usually due to aminoglycosides (gentamycin), amphotericin, contrast-This has a different necrosis pattern than ischemic ATN-Toxic ATN affects close to all of the PT, as well as the thin ascending limb-Necrosis in the PT is extensive and continuous (broken up and focal in ischemic ATN)

Answer 336

-Dominant form of PKD is seen in adults (less severe), whereas the recessive form is seen in infants (very severe)-In ADPKD there are expanding cysts that eventually destroy the renal parenchyma and cause renal failure-These cysts are not present at birth-Micro: variably-sized cysts lined by simple epithelium w/ normal intervening parenchyma present-Associated abnormalities: liver/pancreatic cysts, cerebral aneurysms/rupture, ao regurg/valve anomalies-Causes of death: uremia-Complications: MI, CHF, ICH, ruptured berry aneurysm

Answer 337

-Seen in infants, not normally compatible w/ life-Cysts are more uniform in size/shape than in adult form-Associated congenital abnormalities: cystic liver disease and biliary dysgenesis w/ hepatic fibrosis leading to portal HTN-Death due to rapid renal failure

Answer 338

-MSK and UMCD are identical in almost every way, except that UMCD pts have Sx and MSK pts do not have Sx-Both have kidneys w/ small cysts mostly in medulla/corticomedullary junction-Sx in UMCD: polyuria/polydipsia (due to tubular defect in concentrating ability), Na wasting and tubular acidosis-Other forms of cystic diseases: simple renal cysts (no clinical significance) and dialysis cystic disease (from chronic dialysis)

Answer 339

-Filling: unidirectional peristalsis down ureters to bring urine to bladder-Bladder stretches (high compliance) and is in a low pressure state-Normal voiding: First SNS to sphincter decreases and sphincter opens. Then PsNS increases and causes bladder to contract (low pressure)-If obstruction is btwn bladder and kidney it is upper urotract (must be bilateral to produce renal Sx but still can produce)-If obstruction is btwn bladder and end of urethra it is lower urotract (anywhere will produce Sx)

Answer 340

-Congenital: atresia of urethra, meatus stenosis, presence of valves in either ureter or urethra-Acquired: calculi (stones), infection/inflammation, hyperplasia (BPH), pathophysiological, trauma

Answer 341

-Acute: renal colic (groin/ab radiating to flank pain comes in peristalsis), often from stones-Chronic: dull pain, ache, pressure (recurrent UTI)

Answer 342

-Irritative + obstructive Sx-Irritative Sx: dysuria, urge incontinence, nocturia, increased frequency and urgency-Obstructive Sx: decreased force of stream, dribbling, hesitancy, intermittency, incomplete emptying-See an increase in post-void residual (PVR)-By far most common is BPH in a man-If its chronic bladder outlet obstruction: bladder hypertrophy and detrusor (SM part of bladder wall) dysfxn

Answer 343

-Renal insufficiency may be seen either in acute or chronic obstructions, depends on degree of obstruction, presence of bilateral kidneys, and baseline renal function-Response to obstruction: altered renal blood flow, change in GFR, loss of concentrating ability w/in collecting duct-Dilation of renal tubules, first in collecting duct then extends proximally (gloms affected last)-Can see fibrosis, mac infiltrate, hemorrhage/necrosis-Radiographic changes: bladder trabeculation, diverticuli, calculi, J hooking of ureter, hydronephrosis, thinned parenchyma

Answer 344

-Urethral obstruction: bladder dilation and hypertrophy, dilated ureter, dilated renal pelvis and calyces (hydronephrosis) all bilateral-Outflow obstruction: bladder SM hypertrophy and hyperplasia (bundles of SM form trabeculi)

Answer 345

-Can be seen in any kind of urinary tract obstruction-Hydronephrosis is characterized by dilated calyces and dilated pelvis w/ thinning of the medulla and cortex, chronically can lead to HTN-Micro: early there is dilation of tubules, followed by tubular compression and atrophy-Can also see interstitial fibrosis and normal gloms-Hydroureter (seen in hydronephrosis): dilation, hypertrophy and hyperplasia of SM due to chronic increase intraluminal pressure + chronic infl cells

Answer 346

-Nephrostomy + bladder catheter and measure pressure difference-If difference is 22cmH20 there is an obstruction-Btwn 15-22cm H2O and its undetermined

Answer 347

-Calculi: renal colix and hematuria-BPH: urinary bladder syndrome (hesitancy, straining, dribbling, frequency, dysuria)-Infection: fever, frequency, urgency, pyuria, leukocytosis, bacteriuria, dysuria, ab pain-HTN common in longstanding hydronephrosis-Renal failure (uremia): high BUN, Cr, anemia, lethargy, nausea, vomiting, mental changes

Answer 348

-Infection: stasis of urine promotes infection (urethritis, prostatitis, ureteritis)-Renal failure: due to suppression of glomerular filtration and ischemic atrophy of the kidney-Acute complete urinary tranct obstruction causes shut down of renal function and very little or no hydronephrosis-Intermittent or partial urinary tract obstruction results in hydronephrosis

Answer 349

-Hyperplasia of stroma and epithelium (usually w/in transition or periurethral zone)-Most common cause of urinary tract obstruction-Begins 5-6th decade, hormones play important role-Prostates have enlarged, nodular surface (normal is smooth)-BPH tends to affect the medial lobe of the prostate, where as prostate cancer tends to affect the lateral lobes

Answer 350

-Micro: there is a nodular appearance to the area of hyperplasia-At a higher mag, BPH is associated w/ tubuloalveolar glands that are dilated or w/in foldings of the epithelium (increased number of folds)-BPH leads to obstructive and irritative Sx, and Sx are not always related to enlargement-Signs: bladder hypertrophy, trabeculation

Answer 351

-Acute: periglandular-intraglandular infiltrate-Predominantly PMNS and usual cause is infection-Chronic prostatitis: largely an interstitial infiltrate w/ mononuclear cells and unknown cause

Answer 352

-Urinary retention-Infection-Bladder decompensation-Calculi (!)-Hematuria-Hydronephrosis-Renal failure

Answer 353

-Rx is remove the obstruction (site and cause of obstruction dictates Rx)-Post-obstructive diuresis: after relief of unilateral ureter obstruction of solitary kidney or relief of bilateral ureter obstruction-Physiologic post obstructive diuresis: self-limiting-Pathologic: impaired concentrating ability or Na reabsorption (rare)

Answer 354

-Men and women roughly equal incidence, prevalence increasing-Relapse associated w/: young age of onset, family Hx, infection stones, underlying condition (hTPH)

Answer 355

-80% are Ca oxalate-CaPO4-Struvite (infection stones for proteus)-Uric acid-Cystine

Answer 356

-Ca stone are most common and often form when there is hypercalcuria (not necessarily hypercalcemia)-Supersaturation (normal) may worsen due to an increase of solute or decrease in urine volume-At some point, spontaneous nucleation and homogenous nucleation (crystal growth) occur-Heterogenous nucleation: a crystal of one type serves as a nidus on which another compound precipitates (commonly seen as uric acid nidus precipitating CaOx stone)

Answer 357

-Citrate (! most important)-Mg-Pyrophosphates-Proteins-pH of urine-Uric acid and cystine will precipitate and form crystal in acidic urine-Ca stone will form crystals in alkaline pH urine

Answer 358

-Predisposing factors: dehydration, hypercalcemic conditions (hyperparathyroidism, cushings, sarcoidosis), bladder obstruction (stasis), congenital d/o (PKC, MSK, calyceal diverticuli)

Answer 359

-Monohydrate: very hard crystals-Dihydrate: more soft-Risk factors: hypercalcuria, dehydration, hypocitraturia-Form in alkaline urine

Answer 360

-"metabolic stones"-Can be due to hyperparathyroidism, RTA, sarcoidosis-Form in alkaline urine

Answer 361

-Mg ammonium phosphate-Forms in alkaline urine-Caused by bacteria (proteus) w/ ukase nz-soft and may conform to shape of collecting system (stag horn)-More common in women and in men w/ prostatitis

Answer 362

-Can be due to hyperuricosuria and/or gout-Risk factors: dehydration, gout, uricosuric drugs-Forms in acidic urine-Hyperuricosuric states: gout, lesch-nyhan syndrome, myeloproliferative (tumor lysis)

Answer 363

-Due to genetic inability to reabsorb cystine, ornithine, lysine, arginine in PT-Very hard stones-Forms in acidic urine-Cystine in urine reacts w/ nitroprusside-Most important for Rx: increase fluid intake

Answer 364

-First there is accumulation of crystal deposits around LOH-Then there are crystal deposition in papillary tissue-The stones form on a plaque (randall's plaque)-The plaque corresponds to urine Ca level and urine volume-Amount of plaque corresponds to number of CaOx stones

Answer 365

-Inability to excrete acid, acidosis leads to loss of Ca from bones-Hypocitraturia occurs due to acidosis of urine-Hypercalcuria + hypocitraturia + alkaline urine = Ca stones-Can lead to recurrent disease and nephrocalcinosis-Rx using Kcitrate

Answer 366

-Calcifications of renal papilla/tubules-Distal RTA and MSK can cause stones and nephrocalcinosis

Answer 367

-Sx: pain, hematuria, UTI, sepsis-Ab tenderness, on UA there is RBC, WBC, crystals-Dx best is CT (can also ultrasound-Hx/PE: family Hx, prior stone Hx, recurrent UTI, systemic disease-Rx: anlagesia, hydration, hospitalization if systemic infection-80-90% of stones pass-Alpha blockers and Ca blockers an option if stone doesn't pass-May have to be removed if: infection, solitary kidney, intractable pain, renal failure

Answer 368

-Thiazides stimulate Ca reabsorption in PT/DT and decrease Ca excretion by 30%-Decrease recurrence of stone formation-SEs: hypercalcemia, hyperuricemia, hypokalemia, hyponatremia, dehydration, hypomagnesia

Answer 369

-Fluids, alkalization of urine w/ K citrate-Allopurinol if hyperuricosuria

Answer 370

-Fluid intake >2 L /day-Decrease Na intake-Do not restric Ca-Avoid carbs/sugar-Moderate protein (esp. animal protein)-Increase citrate consumption

Answer 371

-Acetohydroxamine (urease inhibitor) to prevent recurrence

Answer 372

-Small amount of amniotic fluid, presence indicates mechanical urinary tract obstruction, bilateral renal agenesis, or severe ARPKD-If present <30 wks; highly correlated w/ pulmonary insufficiency-If present after 30 wks, there is minimal pulm insufficiency-Bilateral renal agenesis (potters syndrome): severe oligohydramnios w/ fetal death due to pulmonary hypoplasia (fetus has flat face, low ears, extremity deformities)-Renal a genesis can be due to abnormalities of development of the pronephric-mesonephric-metanephric system or from failure of development of ureteric bud

Answer 373

-Renal hypoplasia: reduction in nephron number and size of kidney w/ normal renal tissue-Renal dysplasia: misplaced ureteric bud results in abnormal nephrogenesis w/ abnormal differentiation (non-functional nephrons)-Non inherited cyst formation in renal parenchyma (cartilage cysts)-Usually unilateral, but can be bilateral (then must be distinguished from PKD)-Often clinically significant and account for majority of peds pts w/ ESRD

Answer 374

-May be secondary to ureteropelvic junction (UPJ) obstruction (UTI)-Male: consider posterior urethral valves-Female: consider ectopic ureteroceles-Will not be evident until 16-18th week of gestation

Answer 375

-Chronic obstruction leads to loss of nephrons, may have dysplasia along w/ obstruction-Signs of obstruction: ab mass or dissension, abnormal urinary stream, UTI, palpable flank or suprapubic mass-Ureteropelvic junction obstruction: muscle abnormality, aberrant blood vessels, abnormal angle of insertion-No dilated ureter (obstruction is upstream)

Answer 376

-Ureterovesico junction obstruction: ureteroceles (cyst-like enlargements of the lower end of the ureter), vesicoureteral reflux, abnormalities of ureter insertion into bladder-Dilated ureter (obstruction is downstream)-UVJ obstuction: will have dilated ureter (obstruction is distal to ureter)-UPJ obstruction: will not have dilated ureter (obstruction is proximal to ureter)-Posterior urethral valves (only in males): mucosal folds obstruct bladder outflow at the distal prostatic urethra-Pts present w/ absent urinary stream or dribbling and generally leads to renal failure

Answer 377

-Horseshoe kidney: kidneys are fused at lower pole located in lower abdomen b/c can't ascend due to IMA-Migration: disruption of ascent of kidneys (one or both)-Ectopic kidneys: both kidneys may be on the same side, or other problems w/ migration-Duplicated collecting systems: arise from abnormal branching of the ureteric bud-Early branching results in a duplicated kidney, ureter, and visicoureteral junction-Late branching results in a single kidney and 2 ureters

Answer 378

-Physical limitations-Psychological-Social-Domestic-Ocupational-Sexual

Answer 379

-Continence is learned: cognitive control over a reflex arc-Bladder is SM, internal sphincter is SM, external sphincter is striated and SM-Somatic nerves (pudendal nerves) relay to CNS bladder fullness-These nerves will also provide somatic control of the external sphincter -Before learned continence, this afferent signal causes a reflex efferent signal thru the pelvic nerves (PsNS) to relax the sphincter and initiate detrusor contraction and voiding

Answer 380

-This process is what causes normal voiding even after continence is learned-What controls continence is an SNS efferent stimulation (via hypogastric nerves) that causes constriction of the bladder neck and urethral sphincters to prevent voiding, while also inhibiting the PsNS reflex-When there is conscious desire to urinate, the SNS reflex is shut allowing the PsNS and somatic stimulation to permit voiding

Answer 381

-Brain: cortex inhibits voiding and pons facilitates voiding-Spinal cord: spinal tract and nuclei-Local: pudendal nerve somatic sensory (afferent limb of reflex arc) and pelvic nerve PsNS (efferent limb of reflex arc)-Sympathetics: increase sphincter tone, but little clinical significance-PsNS (pelvic nerve): required for detrusor contraction-Somatic sensory (pudendal nerve): sensation of bladder fullness-Cerebral cortex: required for detrusor-sphincter coordination, inhibits reflex arc

Answer 382

-Bladder fills under low pressure (high sphincter pressure), and urge to void increases as bladder is stretched-Continence allows us to inhibit the reflex arc (via suppression of PsNS efferent limb) by cortex-Pons will disinhibit the PsNS reflex to allow for voiding when acceptable-Voiding: relaxation of urethral sphincter followed by bladder contraction until empty

Answer 383

-Filling: poor compliance, overactive bladder, poor sphincter activity, disruption in communication btwn bladder and brain (injury to cortex)-Storage: overstretched detrusor (chronic obstruction, loss of sensation), injury to spinal cord or pons-Emptying: non-relaxation of outlet, obstructed outlet, poor bladder contraction (areflexia: motor, sensory, neurogenic origins)

Answer 384

-Idiopathic (non-neurogenic): must rule out other issues like BPH, UTI, bladder tumor, stones -If these are ruled out idiopathic is over active bladder (OAB)-Neurogenic: UMN or LMN -Can be from MS, spinal cord injury, transverse myelitis, CVS, parkinson's-UMN: can affect bladder (detrusor overactivity) or sphincter (dyssynergy)

Answer 385

-LMN: can affect bladder (areflexic) or sphincter (decreased response)-Lesions at or above brainstem: intact sensation and sphincter, w/ detrusor overactivity-Lesions at the spinal cord: detrusor overactivity w/ dyssynergic sphincter, sensation variable-Lesions distal to spinal cord: bladder areflexic, sensation variable, sphincter variable

Answer 386

-Failure to empty: b/c of bladder or outlet-Failure to store: b/c of bladder or outlet-Incontinence is failure to store-B/c of urethra: stress urinary incontinence-B/c of bladder: urge incontinence (OAB)

Answer 387

-Stress urinary incontinence: due to poor outlet resistance (sphincter problem)-Sx: cough, sneeze, exercise all cause voiding-Dry at night or when sedentary w/ little frequency or urgency-Often small volume-Urge incontinence: due to OAB, but may be mixed (w/ SUI)-OAB usually idiopathic/neurlogic-Sx: urgency prior to leakage or leakage w/o awareness-Wet at night w/ frequency, urgency, no relationship to activity-Often large volume, frequent urge to void, "can't make it to bathroom"

Answer 388

-Due to failure to empty-Sx: straining to void, poor sensation, frequency-Can be neurologic, BPH, prostate CA, stricture, diabetes

Answer 389

-Pads, behavior Rx, meds, neuromodulation, surgery-Behavioral Rx: diet, timed voiding, pelvic exercises, reinforcement, delayed voiding-Meds (anticholinergics): increase volume to bladder contraction, time btwn voids, does not increase warning time, decreases magnitude of bladder contraction

Answer 390

-A decrement in GFR <15

Answer 391

-Most important cause of CKD is diabetes-Proteinuria-HTN: goal for BP isnt as large of a risk factor w/o proteinuria-But w/ proteinuria HTN is a substantial negative risk factor

Answer 392

-Rx the underlying cause of the disease-This includes giving ACEIs/ARBs, statins for hyperlipidemia

Answer 393

-Metabolic derangements-CV complications-CKD mineral bone d/o-Anemia, platelet dyfxn-Metabolic complications arise as GFR declines and excretion of certain solutes declines as well-Impaired excretion of: Na, K, PO4, H+, uric acid-Also impaired urinary dilution and concentration

Answer 394

-Manifestations: fatigue, weakness, pruritus, pallor, anorexia, nausea, vomiting, insomnia, irritability, confusion, hyperreflexia, dyspnea, edema, pericarditis-Labs: metabolic acidosis, hyperphosphatemia, hypocalcemia, hyperkalemia, anemia, hyperuricemia, broad waxy casts

Answer 395

-IHD: accelerated atherosclerosis-HF: chronic volume overload, vascular calcification, cardiac ischemia-Arrhythmias: cardiac remodeling + metabolic derangements

Answer 396

-PTH levels rise in CKD due to the combination of: decreased vit D, hyperphosphatemia, hypocalcemia-Hypocalcemia (due to low levels of vit D- made in PT) leads to increase in PTH release (PTH increases bone turnover to release Ca and PO4 into blood)-W/ declining GFR excretion of PO4 decreases-High PO4 levels further stimulate PTH and increases FGF23 levels to increase renal PO4 excretion-The kidney, however, cannot excrete the PO4 appropriately so PO4 levels remain high-FGF23 also normally inhibits PTH release, however in the setting of CKD there is both high FGF23 and PTH thus the parathyroids become resistant to the FGF23

Answer 397

-Osteitis fibrosa cystica: high bone turnover w/ increased PTH-Increased osteoclast activity causes an irregular woven collagen matrix thats weak-Adynamic bone: low bone turnover, w/ low PTH-Overall little bone formation

Answer 398

-Restrict PO4 in diet-PO4 binders w/ meals-Screen for vit D deficiency and Rx-Monitor PTH, correct hypocalcemia

Answer 399

-EPO deficiency: normocytic anemia-Anemia more prevalent when GFR <30-CKD pts have impaired Fe absorption (mediated by hepcidin)-Can give EPO, but has adverse effects: HTN, stroke, thrombosis, RBC aplasia, Fe deficiency, malignancies

Answer 400

-Hemodialysis or peritoneal dialysis-Principles of Rx: solute clearance and volume removal-Primary mechanism of solute removal is diffusion-Primary mechanism of fluid removal is hydrostatic pressure-Diffusion is used to achieve desired electrolyte concentrations (i.e. can give back Ca by using a high Ca dialysate)-Peritoneal dialysis: blood is filtered indirectly (peritoneal membrane is filter-Diffusion occurs btwn blood in the capillaries of the peritoneal membrane and dialysate in the peritoneum

Answer 401

-Epithelial tumor of the kidney composed of large cells w/ small uniform nuclei and abundant eosinophilic cytoplasm-Are encapsulated, brown and uniform w/o any yellow areas, necrosis, or hemorrhage-Lesion is centrally located "star scar" (stellate shape)-Micro: uniform cells w/ small nuclei and absence of mitotic activity

Answer 402

-Occurs sporadically and in pts w/ tuberous sclerosis (TSC1/2 mutations)-Tuberous sclerosis is familial disease characterized by brain tumors, leading to epilepsy, retardation, and multiple skin lesions-Angiomyolipomas tend to be unilateral and solitary if sporadic, and multiple/bilateral if from tuberous sclerosis

Answer 403

-These tumors are well circumscribed and usually in renal cortex-3 main components under micro: mature fat, abnormal blood vessels, and spindle cell proliferation that resembles SM-There are dysmorphic blood vessels w/ SM-like cells radiating out from them-Hemorrhage is very common (due to dysmorphic blood vessels)

Answer 404

-75% of all malignant kidney neoplasms, associated w/ KO of VHL tumor suppressor gene -Carcinomas in kidneys arise from epithelial tubule cells and thus are adenocarcinomas-Risk factors for CCC: smoking, obesity, uncontrolled HTN-Clinical presentation: classic triad of hematuria, flank pain, and mass-May present w/ left sided vericocele (tumor blocks drainage of left spermatic vein into L renal vein)-Other Sx include nonspecific ab pain, GI complaints, weight loss, paraneoplastic syndrome (EPO, renin, PTHrP, ACTH)

Answer 405

-Possible comorbidities: anemia, HTN, hepatic dysfxn, fever-Presence of Sx (especially weight loss) suggests poorer prognosis-Pts w/ hypercalcemia or hepatic dysfxn must be evaluated for possible metastases (bone, brain, lung, liver)-The tumors also can grow into the lumen of the renal vein and vena cava as a tumor thrombus-CCC masses are usually solitary and unilateral, usually large, round, and usually w/ fibrous capsule-They have some yellow areas of fat, and white and grey areas of necrosis

Answer 406

-Micro: large cells w/ clear cytoplasm arranged in solid nests or alveolar structures, the nests being separated by a prominent vascular network-Gading based on nuclei and how pleomorphic they are (1 being no pleomorphism, 3 being pretty pleomorphic) -Gade 4 tumors lose their architecture and all the cells become more spindle shaped, pleomorphic and resemble a sarcoma (sarcomatous renal adenocarcinoma)

Answer 407

-95% in children under age 10 (2-10 yo typically)-A nephroblastoma that presents as a palpable mass, can cause hematuria, pain, or failure to thrive-Tumors are usually unilateral, large and globular-Micro: undifferentiated (anapestic) small ovoid cells w/ hyper chromatic nuclei and little cytoplasm (composed of blastema- primitive cells that give rise to metanephros and eventually kidney- look like a sea of small blue cells)-These tumors necrose and have a high mitotic rate (lots of mitotic figures)-The tumors show tubule-like structures, primitive gloms, and a variety of mesenchymal cells (cartilage, skeletal muscle, and bone)-Grade is most important prognostic factor (anaplasia = bad)-These can spread to lung, liver, bone, brain

Answer 408

-Tumors may arise in the urothelium of the renal pelvis, ureters, bladder, and urethra (90% occur in the bladder- AKA bladder CA, but after bladder most commonly found in renal pelvis) and are usually transitional cell CA-Transitional epithelia found from the papillae to the urethra (female) or membranous urethra (male)-Risk factors: cigarette smoking is strongest factor-Sx: almost all pts present w/ microscopic hematuria, and gross painless hematuria in pts over 40 is bladder CA until proven otherwise

Answer 409

-Papillary pathways (below): go from low grade-> high grade-> invasion-Grade I: papillary structures lined by thickened transitional epithelial cells w/ normal cytologic features -Grade II is similar to grade I but w/ more abnormal cytologic features-Grade III: either papillary or solid growth w/ marked cytologic atypia and increased mitotic activity, often w/ squamous and glandular metaplasia

Answer 410

-Flat pathway (CIS): go from high grade (CIS)-> invasive, associated w/ p53 mutations-Transitional cell carcinoma in situ (usually multifocal: flat lesion w/o obvious gross abnormalities, but the urothelium shows cytologic abnormalities of grade III transitional cell CA (probably precursor to grade III)-Low grade tumors are often multifocal, tend not to invade/metastasize, whereas high grade tumors will invade and metastasize to LN, lung, bone, liver

Answer 411

-Most often metastasizes to bone (and LNs)-Associated w/ translocation of ERG gene-Most common CA in men-Usually pts present w/ elevation of serum PSA or a nodule on rectal exam in completely ASx men (BPH can also raise PSA)-Sx occur late in course, and are usually voiding complaints, back pain, or bone pain-Usually affects the peripheral part of the prostate gland

Answer 412

-Micro: small irregular infiltrating glands lined by a single layer of malignant cells-The lack of basal cell layer distinguishes these glands from benign glands-Benign glands will have this basal cell layer (which stains for k903), but prostate CA glands will not-The glandular cells have large nuclei w/ prominent nucleolus-Usually pts present w/ grade 3 (small regular glands), grade 4 (increased glandular irregularity) or grade 5 (single cells that do not form glands)

Answer 413

-Infection of the lower urinary tract (i.e. bladder)-Almost all UTIs are due to E coli (or other gram negative enterobacteria)-Sx of cystitis: dysuria, urgency, increased frequency, suprapubic tenderness, pelvic discomfort, small volume voiding, increased number of WBCs in urine (pyuria)

Answer 414

-Ascension of the bacteria into the kidney (usually) or from hematogenous spread (rarely)-Sx similar to cystitis, but in addition: fever, flank pain, costovertebral angle (CVA tenderness, nausea, vomiting-Should always do urine culture and susceptibility test-Rx w/ fluoroquinolones or other antibios based on local resistance-Do not need to extend duration of Rx if bacteremia unless endocarditis present

Answer 415

-Mostly females, except neonates (M>F)-In adults, most male UTIs are prostatitis-Risk factors: abnormalities of the urinary tract (obstruction), catheters, DM, immunosuppressed pts, sexual intercourse, neurogenic bladder, bladder prolapse, pregnant women

Answer 416

-First there is vaginal colonization and ascent via urethra-Bacterial adhesion factors (fimbriae) allow the E coli to bind to epithelial cells-The bacterial can penetrate cells to form intracellular reservoirs w/in the mucosa and serve as a source of recurrent infection-LPS from E coli induces release of cytokines and allows for easier entry into bladder-Other type of bacteria thats not GN enterobacteria: staph saprophyticus (also maybe strep)

Answer 417

-Seen in UTIs of pts recently from middle eastern countries-Causes a macroscopic hematuria w/ dysuria and urinary frequency-Can lead to bladder CA

Answer 418

-If resistance rate is >20% then don't use that antibio (ampicillin, amoxicillin)-Fluoroquinolones are best bet (<10%)-Virulence mechanisms (fimbriae) present in 80% of pyelonephritis cultures and 60% of cystitis

Answer 419

-Cystits: dysuria, frequency, urgency, suprapubic pain and/or hematuria-Pyelonephritis: fever, chills, flank pain, nausea, vomiting, sepsis, multi-organ dysfxn, shock + cystitis Sx-Dysuria may be from vaginitis or urethritis esp if there is discharge or foul odor

Answer 420

-PE: fever, CVA tenderness, ab exam-Labs: urinalysis, urine culture-Urinalysis: pyuria present in almost all cases (absence suggests alternative Dx)-Nitrate test is sensitive, specific to enterobacteria (will not pick up strep/staph)-Urine culture only if Sx persist w/in 3 mo of antibio initiation, in women w/ negative leukocyte esterase but positive Sx, all women w/ suspected pyelonephritis, and all men w/ Sx-Sterile urine: test for atypical organisms (TB, chlamydia, ect), uroepithelial tumor, interstitial cystitis

Answer 421

-Up to 40% of elderly men and women-Only 3 groups would benefit from Rx: pregnant women, renal Tx pts, pts undergoing genitourinary tract procedures

Answer 422

-Nitrofurantoin-Trimethoprim-sulfamethoxazole (bactrim)-Fluoroquinolones

Answer 423

-Relapse: infection w/ same organism-Recurrence: infection w/ different organism-Antibio prophylaxis does not appear to prevent recurrence-Complicated UTIs: due to anatomical (enlarged prostate) or pharmacological factors that predispose pt to persistent infection, recurrent infection, or Rx failure

Answer 424

-Occurs in young and middle-aged men-Usually E coli, may also be other enterococcus, proteus-Sx: fevers, chills, malaise, dysuria, low back pain, painful ejactulation-Almost all male UTIs due to prostatitis-Always do gram stain and culture-Antibios for 4-6 wks-Fever abates and dysuria disappears w/in 2-6 days-Negative urine culture at 7 days predicts cure in 4-6 wks-Prostatic abscess should be considered when clinical abnormalities persist despite appropriate Rx