Renal Flashcards

Question

T/F - The border between outer and inner stripe of the outer medula is determined by where all the descending limbs of all nephrons begin (all at the same level)

Answer 1

FALSE - they do begin at the same level, which marks the inner and outer medulla border.

Answer 2

The macula densa

Answer 3

- Up to the DCT, the epithelial cells forming the wall of a nephron in any given segment are homogeneous and distinct for that segment. - In the DCT -> the epithelium contains 2 types of cells: * Principal cells -> majority * Intercalated cells -> intercalated between principal cells.

Answer 4

Regulates nephron's blood flow and kidney's ability to regulate SBP.

Answer 5

1) Granular cells -> differentiated smooth muscle cells in the walls of the afferent arterioles. They contain secretory vesicles with renin inside. 2) Extraglomerular mesangial cells - a continuum with the glomerular mesangial cells but outside the Bowman's capsule (BC). 3) Macula densa cells - detect flow rate and composition of fluid within the nephron at the very end of the thick ascending limb -> control renin secretion.

Answer 6

Filtration Secretion Reabsorption Excretion

Answer 7

Process by which water and solutes in the blood leave the vascular system through the filtration barrier and enter Bowman's space.

Answer 8

- Very much like blood plasma - Contains very little proteins -> large proteins are not filtrated. - Inorganic ions and LMW organic solutes in same concentration as plasma.

Answer 9

The volume of filtrate formed per unit of time. 125mL/min (180L/day -> all other capillaries of the body, approx. 4L/day). Average total volume of plasma in humans: 3L -> entire plasma volume is filtered 60 times / day.

Answer 10

Process of transporting substances into the tubular lumen from the cytosol of epithelial cells that form the wall of the nephron (either synthesized there, or coming from the blood).

Answer 11

Process of moving substances from the lumen across the epithelial layer into the surrounding interstitium and then into the blood.

Answer 12

- They extract nutrients and metabolize them as dictated by the cell's own nutrient requirements. - They also do other metabolic transformations directed toward altering the composition of urine/plasma. - Most important: * Gluconeogenesis * Synthesis of ammonium from glutamine * Production of bicarbonate

Answer 13

- Neuronal signals -> originate in the sympathetic celiac plexus. - Hormonal signals -> from adrenal gland, pituitary, parathyroid and heart. - Intrarenal chemical messengers - originate in one part of the kidney and act in another part -> NO, superoxide, eicosanoids... also influence basic renal processes.

Answer 14

About 20% of the resting CO

Answer 15

To the cortex. Then 5-10% of that cortical blood flow is directed to the medulla before returning to the systemic circulation.

Answer 16

* Blood enters each kidney at the hilum via a renal artery * After several divisions into smaller arteries blood reaches arcuate arteries that course across the tops of the pyramids between the medulla and cortex. * From these, interlobular arteries (also called cortical radial arteries) project upward toward the kidney surface. * These arteries give off numerous arterioles, each of which leads to an individual Bowman’s capsule and the glomerulus within. * These arteries and glomeruli are found only in the cortex, never in the medulla. * The arterioles leading to glomeruli are called afferent arterioles and have important functional characteristics discussed later. * In most organs, capillaries recombine to form the beginnings of the venous system, but the glomerular capillaries instead recombine to form another set of arterioles, the efferent arterioles. * The vast majority of the efferent arterioles soon subdivide into a second set of capillaries called peritubular capillaries / vasa recta. * These capillaries are widely distributed throughout the cortex in close proximity to the tubular segments. * The peritubular capillaries then rejoin to form the veins by which blood ultimately leaves the kidney.

Answer 17

- Blood viscosity - Vessel length - Vessel RADIUS -> see formulas, Poiseuille's law

Answer 18

Because it describes the relationship between radius and resistance -> resistance can be controlled physiologically via small changes in vessel radius, mediated by arteriole smooth muscle.

Answer 19

In the glomerular capillaries. This difference is crucial for function -> leads to net filtration in glomerulus and reabsorption in peritubular capillaries.

Answer 20

1) Endothelial cells of the capillaries, is perforated by many large fenestrae, which occupy about 10% of the endothelial surface area. They are freely permeable to everything in the blood except red blood cells and platelets. 60-80nm. 2) The middle layer, the capillary basement membrane, is a gel-like acellular meshwork of glycoproteins and proteoglycans, with a structure like a kitchen sponge. It has negative charges, repelling negatively charged molecules (like albumin). 3) The third layer consists of epithelial cells (podocytes) that surround the capillaries and rest on the capillary basement membrane. The podocytes have an unusual octopus-like structure. Arms extend from the soma and wrap around several nearby glomerular capillaries. Small “fingers,” called pedicels (or foot processes), extend from each arm and are embedded in the basement membrane. The spaces between the pedicels, called slits, are the passageway through which the glomerular filtrate passes. The pedicels are coated by a thick layer of extracellular material, which partially occludes the slits. 30-40nm. 4) Finally, extremely thin processes called slit diaphragms bridge the slits between the pedicels.

Answer 21

Molecular size Electrical charge

Answer 22

FALSE - negative filtered to a LESSER extent, positive to a GREATER extent

Answer 23

Heparin sulfate on the lamina rara interna and externa

Answer 24

1) Electrolytes: HCO3–, Na+, K+, Cl–, Ca2+, Mg2+, H2O * Despite the negative charge on some of these electrolytes, they’re very small; hence, they will get freely filtered 2) Non-negatively charged low-molecular weight molecules: glucose, amino acids, lipids, urea, creatinine, vitamins.

Answer 25

- Glomerular hydrostatic pressure GHP - Colloid osmotic pressure COP - Capsular hydrostatic pressure CHP - Capsular oncotic pressure CoP These are known as the Starling forces NFP = (forces that want to push out) - (forces that want to push in) NFP = (GHP + CoP) - (COP + CHP) NFP = (55 + 0) - (30 + 15) = 10mmHg

Answer 26

1) Force that pushes plasma out of the glomerular capsule into the bowman’s space 2) Directly dependent on systolic blood pressure High BP = High GHP Low BP = Low GHP 3) Average value: 55 mmHg

Answer 27

* Exerted by plasma proteins like albumin * Keeps water in the blood * Average value: 30 mmHg Clinical Correlates: • Multiple myeloma: increases amount of proteins in blood -> holds on to more water in the blood -> increases COP. • Hypoproteinemia -> loses substances/proteins -> can’t hold on to water as much -> decreases COP.

Answer 28

As fluid is being filtered out, the pressure will push things back into the capillary bed * By the pressure build-up in the Bowman’s capsule * Average value: 15 mmHg Clinical Correlate: • Renal calculi o Kidney stone stuck in nephron o > 5mm in diameter o Pressure backs up and starts increasing -> increases CHP • Hydronephrosis o Due to renal ptosis o Rapid weight loss o Increased CHP -> more fluid being pushed back into the glomeruli and not much glomerular filtration.

Answer 29

As long as the filtration membrane is intact, there should be no proteins in the Bowman’s capsule -> average value: 0 mmHg

Answer 30

* Plasma volume being filtered out of the glomerulus into the bowman’s capsule every minute * On average, 125 mL/min * Per min., 1.2L goes to AA -> 625mL used in filtration process -> only 20% (125mL) is filtered. GFR = NFP x Kf

Answer 31

As water is filtered out of the vascular space, it leaves most of the proteins behind, thereby increasing protein concentration and hence, the oncotic pressure of the unfiltered plasma remaining in the glomerular capillaries -> NFP decreases from the beginning to the end of the glomerulus.

Answer 32

Raises glomerular pressure and hence GFR

Answer 33

Decreases glomerular pressure and GFR

Answer 34

1) In conditions with low renal blood flow -> oncotic pressure at the end of the capillaries is higher than normal -> will lower NFP and hence, GFR 2) With high renal blood flow -> glomerular oncotic pressure will increase less than normal -> higher NFP -> higher GFR

Answer 35

RPF = the flow of plasma through the glomeruli Filtration fraction: ratio GFR / RPF, normally about 20% -> about 20% of the plasma entering the kidneys is removed from the blood.

Answer 36

TRUE - if relatively more of the plasma is filtered, the increase in oncotic pressure is greater

Answer 37

Glomerular diseases

Answer 38

Is not a change on the Kf within individual glomeruli, rather a decrease in the number of functioning nephrons and this reduces whole kidney Kf

Answer 39

The amount of substance filtered per unit of time. For freely filtered substances, that is the product of GFR x plasma concentration of that substance. Na+ for example: Plasma: 140mEq/L = 0.14mEq/mL Normal GFR = 125mL/min Na+ filtered load = 0.14 x 125 = 17.5mEq/min. What is presented to the rest of the nephron to handle!

Answer 40

Because vascular pressure in the thin-walled glomerular capillaries is higher than in other capillary beds, and hypertensive damage ensues if pressures are too high.

Answer 41

Renal artery pressure -> in a healthy kidney is the same as systemic arterial pressure -> variations on SBP has potential effects on GFR.

Answer 42

Intrinsic mechanisms: * Myogenic mechanism * Tubuloglomerular feedback Extrisinc mechanisms: * Sympathetic NS * RAAS - Renin - angiotensin - aldosterone - ADH system

Answer 43

↑BP → ↑GHP → ↑GFR -> higher glomerular filtration rate (GFR), more urine. Kidneys modulate the GFR so that it is not too excessive making too much urine, or the blood pressure does not remain too high causing injury on the glomerular capillaries. Myogenic response -> blood flows through the afferent arteriole (AA) then to the efferent arteriole (EA) -> ↑BP = more blood to the AA -> Na channels in the smooth muscle of the afferent arteriole are sensitive to stretch -> AA vasoconstricts → ↓glomerular blood flow (GBF) → ↓filtered plasma and other substance (↓GFR)

Answer 44

↓BP → ↓GHP → ↓GFR ↓BP = ↓urine = can cause kidney injury -> how does the kidney prevent it? Mechanism: ↓BP => ↓blood to the AA -> ↓stretch on the AA -> ↓stretch therefore less Na+ enter in the smooth muscle cell → less positive charge → ↓Ca2+ released by the sarcoplasmic reticulum → less contraction => relaxation.

Answer 45

↑BP = ↑GFR o Counteracted by vasoconstriction of AA → ↓GFR ↓BP = ↓GFR o Counteracted by vasodilation of AA → ↑GFR

Answer 46

This mechanism is sensitive to NaCl -> NaCl gets reabsorbed in the proximal convoluted tubule (PCT). 1) ↑BP = ↑GFR = ↑NaCl excretion into the kidney tubules 2) When NaCl transporters in the PCT are saturated, NaCl can escape and move to the LH and then to the DCT where macula densa cells are found o Special NaCl sensors o Release adenosine when it detects ↑NaCl 3) Adenosine functions to: o Vasoconstrict AA → ↓GBF → ↓GFR → ↓NaCl being filtered o Inhibit juxtaglomerular (JG) cells → ↓renin → ↓blood pressure

Answer 47

↓BP = ↓GFR = ↓NaCl excretion into the kidney tubules When macula densa cells detect ↓NaCl in DCT, they release PGI2 and nitric oxide (NO) PGI2 and NO function: o Vasodilate the AA → ↑GBF → ↑GFR → ↑NaCl filtered o Stimulates juxtaglomerular (JG) cells → increases renin release → increases blood pressure

Answer 48

↑BP = ↑GFR = ↑NaCl filtered o ↑NaCl detected by MD cells → release adenosine → vasoconstricts AA and inhibits JG cells to release renin. ↓BP = ↓GFR = ↓NaCl filtered o ↓NaCl detected by MD cells → release PGI2 and NO → vasodilates AA and stimulates JG cells to release renin.

Answer 49

1) Stimulus: ↓↓↓SBP → MAP < 65 mmHg o MAP (mean arterial pressure): measure of perfusion o When MAP < 65 mmHg, kidney is not perfused; blood flow is redirected to other “more important” organs such as the heart, brain and muscles. ↓BP → ↓GFR → ↓urine output o ↓blood flow can cause kidney injury o SNS do its best to increase blood flow MECHANISM: 1) ↓BP triggers baroreceptors → CN IX and CN X send less signals to the medulla oblongata (vasomotor center) 2) Vasomotor center activates sympathetic nerve fibers in the thoracic part causing release of NE and epinephrine, that will act in different systems: a) Heart NE and epi stimulate the β1 receptors in the nodal system and contractile fibers → ↑HR and ↑SV (due to ↑contractility) respectively → ↑CO → ↑BP -> to increase blood flow in the kidneys to avoid injury. Chronotropic: change in heart rate / Ionotropic: change in contractility b) Renal afferent and efferent arterioles -> NE and EPI will act on the α1 receptors of the AA and EA → vasoconstriction → ↓GBF → ↓GFR YES, the goal is to increase the blood flow towards the kidney BUT in sympathetic crisis, the SNS DOES NOT respect the kidneys c) Systemic vessels -> NE and EPI act on the α1 receptors on the systemic vessels → vasoconstriction of multiple vessels → ↑systemic vascular resistance (SVR) → ↑BP d) Juxtoglomerular Cells -> NE and EPI stimulate the β1 receptors on the JG cells → ↑renin → activates angiotensin II →→→ ↑BP

Answer 50

Increase HR and SV Vasoconstriction of the renal afferent and efferent arterioles Vasoconstriction of the systemic vessels → ↑SVR Triggers release of renin from the JGA The effects are the exact opposite when the blood pressure is HIGH.

Answer 51

1) ↓BP → ↓GFR 2) Juxtoglomerular cells are sensitive to changes in blood pressure -> when BP is low, JG cells release renin. 3) Renin cleaves angiotensinogen to produce angiotensin I 4) Angiotensin I move to the capillaries in the lungs and get converted to angiotensin II by angiotensin converting enzyme (ACE).

Answer 52

1) ADH Release -> stimulates the hypothalamus that trigger release of ADH from the pituitary gland. ADH (aka vasopressin or antidiuretic hormone) -> acts on the aquaporin in the collecting duct to reabsorb water -> ↑H2O in blood → ↑blood volume → ↑BP 2) ↑Thirst -> makes you thirsty → ↑water intake → ↑blood volume → ↑BP 3) Aldosterone release -> stimulates release of aldosterone from the zona glomerulosa in the adrenal gland. Aldosterone -> acts on the DCT to make them permeable water and Na+ -> ↑Na+ and H2O reabsorption → ↑BV → ↑BP 4) Vasoconstriction of efferent arteriole and ↑GFR Angiotensin II binds on the receptor on the EA → vasoconstriction of EA -> less blood can escape from the glomerulus, more blood stays in the glomerulus → more blood filtered out → ↑GFR NOTE: Some books say that it also affects the AA; but the effect is much greater in EA (EA >>> AA) 5) Angiotensin II also act on the PCT to cause increased reabsorption of Na+ and H2O -> ↑Na+ and H2O → ↑BV → ↑BP 6) Vasoconstriction of systemic vessels -> acts on systemic vessels → potent vasoconstriction → ↑SVR → ↑BP → ↑GFR

Answer 53

In cases of HIGH BP, JG cells do NOT release renin. Therefore the RAAS does not occur. Atrial natriuretic peptide -> released from the heart in cases of ↑BP and it can block any function of the angiotensin II: a. Blocks ADH release = no water and Na+ reabsorption = urinate water and Na+ = ↓blood volume. b. Blocks aldosterone release = no water and Na+ reabsorption = urinate water and Na+ = ↓blood volume c. Prevents vasoconstriction of EA = ↓GFR d. Causes vasodilation of blood vessels = ↓SVR = ↓BP

Answer 54

Removal of metabolic waste products, ingested substances and excess salts and waters via urine, feces, biochemical transformations in the liver and for volatile substances, exhalation.

Answer 55

2 ways: Plasma half-life -> time it takes for the concentration of a substance in plasma to be reduced by 50% Clearance -> measures the volume of plasma from which all of a substance is removed in a given time.

Answer 56

The substance is removed from the plasma ONLY by the kidneys and is either excreted in urine or catabolized by the renal tubules. The volume of plasma that needs to pass through the kidneys in a given amount of time in order to excrete a given quantity of a substance in the urine

Answer 57

* Because the most commonly used marker of kidney disease (plasma creatinine concentrations) is not sensitive * Plasma creatinine concentrations do not increase until 75% of the nephrons are non functional. * Therefore GFR is much more sensitive.

Answer 58

1) Clearance of exogenous markers - inulin, radioactive markers, iohexol. 2) Clearance of endogenous markers - creatinine, cystatin C, urea. 3) Imaging of the kidneys -> renal scintigraphy, CT.

Answer 59

Inulin clearance - one of the few substances that satisfies the requirement of an ideal marker of GFR.

Answer 60

Practical and common Low cost & convenient Easier than inulin Less invasive Cr clearance is slightly higher than GFR (by 10% to 20%)

Answer 61

- Produced by all nucleated cells at a constant rate. - Only eliminated by kidneys. - All filtered cystatin is removed from the body (no reabsorption) - Production increases with large doses of corticoids. - Production affected by thyroid dysfunction and cancer.

Answer 62

- Less accurate indicator of GFR - Range of normal plasma urea concentrations varies widely depending on protein intake and changes in tissue catabolism. - Urea excretion is under partial hormonal regulation.

Answer 63

- Less accurate indicator of GFR - Range of normal plasma urea concentrations varies widely depending on protein intake and changes in tissue catabolism. - Urea excretion is under partial hormonal regulation.

Answer 64

- Assesses function of each kidney separately - Inject a radiotracer in blood - Measure rise and fall of radioactive counts in each kidney separately

Answer 65

Renal cortex: Fenestrated vascular endothelium—no resistance to passive movement of water and small solutes. Cortical interstitium (between basal membrane and endothelial cells)—similar osmolality and concentration of small solutes to plasma. Renal medulla: Only some fenestrated capillaries. Medullary interstitium is not plasma-like.

Answer 66

Paracellular Transcellular

Answer 67

Transcellular -> through cells -> in on one side, out at the other side Paracelluar -> around cells through tight junctions

Answer 68

- Diffusion - concentration gradient - Channels - pores that allow specific solutes to pass through - Transporters - allow passage of otherwise impermeable substances. * Simporters: 2 substances, same direction * Antiporter: 2 substances, opposite direction * Primary active transporters: require ATP, agains electrochemical gradient. - Receptor mediated endocytosis and transcytosis.

Answer 69

FALSE - faster in the renal cortex

Answer 70

The ability to choose which substance is permitted to move

Answer 71

Both are selective

Answer 72

1) Gated channels: - Ligand - gated -> reversible binding of small molecules - Voltage-gated -> changes in membrane potential - Mechanical distorsion -> stretch gated. 2) Phosphorylation sites -> it can either open or close the channel 3) Some can be moved back and forth between the surface membrane and intracellular vesicles 4) Transcription and expression of channels regulated

Answer 73

A channel is a tiny hole, whereas an uniporter requires that the solute binds to a site that is alternatively available to one side and then the other side of the membrane

Answer 74

Facilitated diffusion

Answer 75

Na-Glu Na-K-2Cl

Answer 76

Na+ / H+ Cl- / HCO3

Answer 77

Move one or more solutes agains concentration gradient, using ATP Na/K ATPase H-ATPase (H out of the cell) CA-ATPase (Ca out of the cell) Multidrug resistance proteins

Answer 78

Transcytosis

Answer 79

Volume of particles per liter of solvent (mol/L). Generally, in the glomerulus, the blood is 300 mOsm/L

Answer 80

1) Sodium-Potassium ATPase -> 3 Na+ out and 2 K+ ions in. * Na+ and K+ move against their concentration gradient -> primary active transport -> requires ATP (97% of K in our bodies is inside the cell). What does it do to the inside of the cell -> decreases Na and increases K. 2) Secondary active transport - passive diffusion of one substance helps facilitate the active transport of another substance (can transport two things at once inside the cell - cotransporter) a) Sodium-glucose cotransporter -> since there’s low Na inside the cell, it’s moving passively along its concentration gradient. Glucose is high inside the cell -> Na+ helps glucose move against its concentration gradient. When it gets into the cell, there are specific transporters on the basolateral membrane that transports glucose out of the cell and into the bloodstream. b) Sodium / amino acids Cotransporter -> transports Na+ inside the cell along with amino acids -> high concentration of amino acids inside the cell. Inside the cell, amino acids have specific transporters that facilitate their diffusion out of the tubular cell and into the blood. c) Sodium-lactate Cotransporter -> passive diffusion of sodium facilitates transport of lactate Assuming normal physiological conditions, 100% of the glucose, amino acids, and lactate get reabsorbed from the kidney tubules into the blood.

Answer 81

How does bicarbonate (HCO3–) gets into the cell? Via CO2 + H2O -> H2CO3 -> H+ + HCO3– o CO2 -> can be found in our blood and can move into the cell (through the basolateral membrane) and react with water to form carbonic acid. o Carbonic acid (H2CO3) -> unstable; dissociates into a proton (H+) and bicarbonate (HCO3–) o What happens to the proton (H+) -> Sodium-hydrogen exchanger -> secondary active transport -> as Na+ moves through the channel to go in the cell, it helps push H+ out -> H+ combines with HCO3– outside of the cell -> H2CO3 is converted by carbonic anhydrase into CO2 and H2O in the lumen of the PCT. o What happens to the bicarbonate (HCO3–)? -> approximately 90% of HCO3– gets pushed into the blood.

Answer 82

Regulation of reabsorption of filtered HCO3- 1) Filtered load -> increases in the filtered load of HC03- result in increased rates of HC03- reabsorption. However, if the plasma HC03- concentration becomes very high (e.g., metabolic alkalosis), the filtered load will exceed the reabsorptive capacity, and HC03- will be excreted in the urine. 2) PCO2 * Increases in PCO2 result in increased rates of HC03- reabsorption because the supply of intracellular H+ for secretion is increased. This mechanism is the basis for the renal compensation for respiratory acidosis. * Decreases in PCO2 result in decreased rates of HC03- reabsorption because the supply of intracellular H+ for secretion is decreased . This mechanism is the basis for the renal compensation for respiratory alkalosis. 3) ECF volume ECF volume expansion results in decreased HC03 reabsorption. ECF volume contraction results in increased HC03- reabsorption (contraction alkalosis). 4) Angiotensin II -> stimulates Na+-H+ exchange and thus increases HC03- reabsorption, contributing to the contraction alkalosis that occurs secondary to ECF volume contraction

Answer 83

* Sodium is very critical in the process of OBLIGATORY WATER REABSORPTION -> when water is obliged to follow sodium (solutes) and move back into the blood. * For example, in the sodium-glucose channel -> when sodium is coming in with the glucose, water feels obliged to follow sodium -> water moves by the process of osmosis, from the kidney tubules into the blood. * About 65% of sodium is being reabsorbed, hence, 65% of water is also being reabsorbed.

Answer 84

About 50% of Cl– and 55% of K+ are reabsorbed via paracellular transport. Very little Ca2+ and Mg2+ are reabsorbed in this area.

Answer 85

Sodium-chloride cotransport -> moves sodium and chloride ions into the cell (in the late proximal tubule) and they are then pushed into the blood.

Answer 86

Lipid-soluble substances can pass through the phospholipid bilayer, like urea. Can pass through the membrane and into the blood. Not all of it gets reabsorbed -> about 50%.

Answer 87

* There are specific protein receptors on the membrane. * If these small proteins are filtered (normally they are not), they can get caught on these receptors * Proteins are endocytosed and taken into the cell, then combined inside the cell with lysozymes (hydrolytic enzymes that break down the proteins into their constituent amino acids). The vesicle then fuses with the cell membrane and amino acids are released into the blood * Receptors are recycled.

Answer 88

* Cotransporter normally brings both Na+ and HPO42– into the cell. * There’s a receptor for the PTH on the basolateral membrane of the cells in the PCT. * PTH binds with the receptor and activates the G-stimulatory protein. * G-stimulatory protein activates adenylate cyclase, activating protein kinase A. * pkA phosphorylates the Na/phosphate cotransporter, inhibiting it. * Phosphates don’t get reabsorbed -> they get excreted.

Answer 89

Glutamine is a specific type of amino acid -> it can undergo deamination, resulting into 2 ammonium ions (NH4+), and the acidified glutamine will be oxidized into 2 bicarbonate ions. Normal blood pH is 7.35-7.45 -> in metabolic acidosis blood pH is low ( < 7.35), and the body has to compensate for that. Bicarbonate resulting from the glutamine metabolism will be taken into the blood to bring the pH back up. In exchange, chloride ion will need to go out of the blood into the cell to maintain electroneutrality. The ammonium ions also produced from the glutamine metabolism will be pushed out of the cell and into the kidney tubule -> it will dissociate into ammonia (NH3) and H+ * REMEMBER - the other mechanism to reabsorb HCO3 and increase blood pH is via CO2 present in the blood and taken into the cells to be converted into H+ and HCO3 and the H+ secreted in the lumen in exchange for Na.

Answer 90

In the blood, there are certain things that we either reabsorb too much or we can’t get rid of - organic bases and acids, like certain drugs (penicillin, cephalosporins, methotrexate), and similar with uric acid, bile salts, morphine, those substances have to be secreted. The process of getting these excreted into the kidney tubules is an active process -> requires ATP.

Answer 91

Two. Ascending limb and descending limb.

Answer 92

* Inside the glomerulus: ~300 mosm -> is the blood plasma * In Bowman’s capsule: ~300 mosm -> sotonic with the blood plasma * When fluid leaves the PCT -> is still at 300 mosm -> it didn’t change because equal amounts of solutes and water were being reabsorbed (due to obligatory water reabsorption). * Medullary interstitial osmolality gets saltier or more hypertonic as we go down the renal medulla -> 300 mosm -> 500 mosm -> 700 mosm -> 900 mosm -> 1200 mosm

Answer 93

Na+/K+/2Cl– cotransporter: * Transports sodium, chloride, and potassium from lumen of filtrate into epithelial cell of ascending limb. * There are specific channels for each ion in the cell -> Na+ and Cl– will be pushed out (towards the medullary interstitium), increasing osmolality. * Only some of the K+ will pass to the interstitium, some of the K+ gets pushed back in the lumen. Creates depolarization of the inner side of the membrane of the ascending limb -> causes Mg2+ and Ca2+ to undergo paracellular transport. IMPORTANT: * The descending limb of loop of Henle is completely impermeable to solutes and permeable to water. * Exact opposite of the ascending limb which is only permeable to solutes, but impermeable to water.

Answer 94

Counter-Current Multiplier Mechanism: * Water will flow out TO the area where the salt is -> from the descending limb to the ascending limb (due to obligatory water reabsorption). * Via Aquaporin-I -> always open in the descending limb of Loop of Henle * Since the medullary interstitial space is saltier as we go down, more water will leave as we go down the descending limb -> by the time the loop of Henle takes a turn to go up, its osmolality will be 1200 mosm -> becomes hypertonic as we move down. * When it goes up, however, the osmolality starts to go down because the ascending limb is losing salt -> by the time it reaches the Distal Convoluted Tubule (DCT) -> the osmolality will be around 120-200 mosm -> hypotonic compared to the plasma.

Answer 95

* Peritubular capillary in the medulla, branching from the Efferent Arteriole * Known as the “Counter-Current Exchanger” * Plasma Osmolality Gradient in medullary interstitium -> 300 -> 500 -> 700 -> 900 -> 1200 * Blood flow to vasa recta is really slow -> function: prevents rapid removal of sodium chloride * Does not develop the medullary interstitial gradient or the counter-current multiplier mechanism -> it’s maintaining the gradient; not generating it. * Vasa recta also delivers oxygen and nutrients.

Answer 96

Descending Limb o H2O permeable o Solute impermeable o Aquaporin-I - allows water to move out to the medullary interstitium Ascending Limb o H2O impermeable o Solute permeable o Na+/K+/2Cl– cotransporter -> pushes these solutes out into the medullary interstitium (salty; high osmolality) -> some K+ gets pushed back in the lumen, creating a depolarization on the inner side of the membrane of the ascending limb -> causes Mg2+ and Ca2+ to undergo paracellular transport. Counter-Current Multiplier Mechanism o Maintained by the vasa recta (vasa recta is the counter-current exchanger).

Answer 97

1) Na-K Pump -> in basolateral membrane, requires ATP -> 3 Na+ ions out and 2 K+ ions in 2) Sodium-chloride symporter -> specialized transporters on the luminal membrane -> sodium and chloride both go into the cell. * Since Na+ ions are going out via the Na-K pump, it means that DCT has high [Na+] compared to inside the cell (going against concentration gradient) * Only 5-6% of Na+ is being reabsorbed here -> 4-5% is left * Cl– will move in together with Na -> Cl- has a special channels in the basolateral mechanism that pumps it into the blood. * THIAZIDE * -> diuretic that inhibits sodium-chloride symporter -> it will affect both the salt and water reabsorption -> instead of reabsorbing the 5-6% back, you’ll lose them to the urine together with a bit of the blood volume

Answer 98

* When there are low blood calcium levels -> stimulate parathyroid gland to secrete PTH * PTH has a receptor on the cell of the distal convoluted tubule -> PTH binds and stimulates the receptor -> G stimulatory protein -> cAMP -> activates protein kinase A * pkA stimulates calcium modulated channels (very sensitive to PTH levels) via phosphorylation -> causes channels to pull in Ca2+ into the cell -> calcium can be bound to protein called calbindin inside the cell, but it will be a low percentage. * Even if blood calcium level is low, there’s still less calcium inside the cell compared to blood -> calcium will be moving against its concentration gradient. Two mechanisms to get calcium out a) Ca2+/Na+ Transporter • Proteins on the basolateral membrane • Pumps calcium out and brings sodium in -> secondary active transport as Na goes down concentration gradient. b) Ca2+/H+ transporter -> uses ATP -> calcium out, H+ in.

Answer 99

* Generally impermeable to water. * Has specialized cells responsible for responding to aldosterone: principal cells -> responsible for mineral and water balance. * Aldosterone -> steroid hormone produced in the globular cells of the adrenal gland * Stimulus for aldosterone secretion: angiotensin-II (wants to increase pressure), hyponatremia and hyperkalemia. Small amounts of CRH can also stimulate its secretion. * Aldosterone passes through the cell’s lipid bilayer because it’s a steroid hormone -> it will activate specific transcription factors to produces different proteins: 1) ) Na channel -> protein embedded in the luminal membrane -> Na is allowed to go inside the cell due to the effects of the Na+/K+ Transporter (low intracellular Na) 2) Na+/K+ transporter in the basolateral membrane -> active transport, uses ATP. Puts 3 Na+ out of the cell, brings 2 K+ in. Na+ would want to go from high concentration to low concentration -> Na+ goes inside the cell via the sodium channel K+ enters the cell -> higher concentration in the cell 3) Potassium channel -> embedded in the luminal membrane -> since there’s high K+ inside the cell, the channel will move it out of the cell where it will eventually be excreted into the urine.

Answer 100

* Can act on the principal cells, together with aldosterone * Presence of ADH will open up the aquaporins-II * Water will have to follow the salt and go into the cell and into the bloodstream -> increases blood pressure.

Answer 101

o Maintain acid-base balance -> keep body within homeostatic range. o Found in the late distal tubule and collecting duct. o Intercalated A cells: acidic conditions. o Intercalated B cells: basic conditions. There are also other cells that could be secreting drugs: toxins, creatinine... and via the intercalated cells we will be secreting H+, HCO3-, ammonium...

Answer 102

They respond to ACIDOSIS (metabolic or respiratory) Scenario: there’s increased CO2 in the blood: o In an acidosis, there is low pH = many protons. o Very little bases to counteract the protons. CO2 + H2O -> H2CO3 -> H+ + HCO3- o Circulating carbon dioxide -> moves into the intercalate A cell, and combines with water to form carbonic acid (catalyzed by CA) o Carbonic acid (H2CO3) -> unstable; dissociates into protons and HCO3– o Protons (H+) -> there is an H+ / K+ ATPase in the luminal membrane -> K+ goes into the cell and H+ goes out, both against concentration gradient. o Bicarbonate (HCO3–) -> will be pumped out of the cell into the blood via the HCO3–/Cl– transporter in the basolateral membrane. o The body needs to secrete substances it doesn’t want, like ammonia (NH3) -> it can be excreted out into the urine where it will combine with the protons secreted to produce ammonium (NH4+).

Answer 103

Responds to ALKALOSIS (respiratory or metabolic) The same pathway as intercalated-A cell, but flipped. o Get rid of bicarbonate instead of the protons o Reabsorb proton into the blood instead of bicarbonate o Increased blood pH -> low H+ and high HCO3- o CO2 + H2O -> H2CO3 -> H+ + HCO3- o CO2 -> found in our blood -> moves into the intercalated B cell, and combines with water to form carbonic acid via CA -> carbonic acid -> unstable -> dissociates into protons and HCO3– o HCO3– goes out of the cell -> pumped out of the cell into the urine via HCO3- / Cl- cotransporter -> Cl- goes into the cell in the luminal membrane via cotransporter and will exit the cell via the chloride channels on the basolateral membrane. o Protons (H+) -> will be reabsorbed via H+ / K+ ATPase in the basolateral membrane (both ions are moving against their concentration gradients) -> K+ goes into the cell, H+ goes out of the cell into the bloodstream.

Answer 104

Cells that maintain mineral and water balance o Hypothalamus has a collection of neurons from the supraoptic nucleus o Their axons move through from the hypothalamus to the posterior pituitary o When stimulated, it will release ADH o ADH will be released whenever the plasma osmolality is changing and can work in the late distal tubule and collecting duct. Second strong stimulus will be low blood volume (will cause the release of ATII -> will stimulate ADH release).

Answer 105

o ADH binds to the vasopressin receptor on the principal cell in the collecting duct of the kidneys -> adenylate cyclase -> activates pkA o Phosphorylates the proteins on intracellular vesicles -> presynthesized vesicles with proteins and channels (aquaporins) o Activates aquaporin-II -> vesicles fuses with the cell membrane o There are aquaporin-III and aquaporin-IV in the basolateral membrane o Water goes into the cell via aquaporin-II, then passes through aquaporins III & IV and goes into the blood -> increases blood volume, and increases blood pressure o Also reaches normal plasma osmolality -> isotonic.

Answer 106

o A lot of urea still gets lost in the urine, but some is recycled -> gets reabsorbed in the last part of the collecting duct. o After all the water has been reabsorbed, urea starts increasing in the tubular lumen o It then moves out of the collecting duct and into the medullary interstitium via facilitated diffusion (lipid soluble). o It gets reabsorbed in the ascending limb of Loop of Henle and it also accumulates outside in the medullary interstitium.

Answer 107

1. Intracellular fluid is two-thirds of TBW. The major cations of ICF are K+ and Mg. The major anions of ICF are protein and organic phosphates (ATP, ADP and AMP). 2. Extracellular fluid is one-third of TBW and is composed of interstitial fluid + plasma. The major cation of ECF is Na+. The major anions of ECF are Cl- and HC03- . a. Plasma is 25% (1/4) of the ECF. The major plasma proteins are albumin and globulins. b. Interstitial fluid is 75% (3/4) of the ECF. The composition of interstitial fluid is the same as that of plasma except that it has little protein. Thus, interstitial fluid is an ultrafiltrate of plasma. 3. 60-40-20 rule TBW is 60% of body weight. ICF is 40% of body weight. ECF is 20% of body weight.

Answer 108

a. Osmolarity is concentration of solute particles. b. Plasma osmolarity is estimated as: Posm= 2 x Na + Glucose/18 + BUN/2.8 => mOsm/L Na+ =plasma Na+ concentration (mEq/L) Glucose = plasma glucose concentration (mg/dL) BUN= blood urea nitrogen concentration (mg/dL) c. At steady state, ECF osmolarity and ICF osmolarity are equal. d. To achieve this equality, water shifts between the ECF and ICF compartments. e. It is assumed that solutes such as NaCl and mannitol do not cross cell membranes and are confined to ECF.

Answer 109

Is also called isosmotic volume expansion. 1) ECF volume increases, but no change occurs in the osmolarity of ECF or ICF. Because osmolarity is unchanged, water does not shift between the ECF and ICF compartments. 2) Plasma protein concentration and hematocrit decrease because the addition of fluid to the ECF dilutes the protein and red blood cells (RBCs). Because ECF osmolarity is unchanged, the RBCs will not shrink or swell. 3) Arterial blood pressure increases because ECF volume increases.

Answer 110

For example, diarrhea. Is also called isosmotic volume contraction. 1) ECF volume decreases, but no change occurs in the osmolarity of ECF or ICF. Because osmolarity is unchanged, water does not shift between the ECF and ICF compartments. 2) Plasma protein concentration and hematocrit increase because the loss of ECF concentrates the protein and RBCs. Because ECF osmolarity is unchanged, the RBCs will not shrink or swell. 3) Arterial blood pressure decreases because ECF volume decreases.

Answer 111

SIADH - gain of water. Also called hypoosmotic volume expansion 1) The osmolarity of ECF decreases because excess water is retained. 2) ECF volume increases because of the water retention. Water shifts into the cells; as a result of this shift, ICF osmolarity decreases until it equals ECF osmolarity, and ICF volume increases. 3) Plasma protein concentration decreases because of the increase in ECF volume. Although hematocrit might also be expected to decrease, it remains unchanged because water shifts into the RBCs, increasing their volume and offsetting the dilut- ing effect of the gain of ECF volume.

Answer 112

Excessive sweat - also called hypertonic volume contraction 1) The osmolarity of ECF increases because sweat is hyposmotic (relatively more water than salt is lost). 2) ECF volume decreases because of the loss of volume in the sweat. Water shifts out of ICF; as a result of the shift, ICF osmolarity increases until it is equal to ECF osmolarity, and ICF volume decreases. 3) Plasma protein concentration increases because of the decrease in ECF volume. Although hematocrit might also be expected to increase, it remains unchanged because water shifts out of the RBCs, decreasing their volume and offsetting the concentrating effect of the decreased ECF volume.

Answer 113

For example, excessive NaCl intake. Also called hypertonic volume expansion 1) The osmolarity of ECF increases because osmoles (NaCl) have been added to the ECF. 2) Water shifts from ICF to ECF. As a result of this shift, ICF osmolarity increases until it equals that of ECF. 3) As a result of the shift of water out of the cells, ECF volume increases (volume expansion) and ICF volume decreases. 4) Plasma protein concentration and hematocrit decrease because of the increase in ECF volume.

Answer 114

Adrenocortical insufficiency. Loss of NaCI. Is also called hyposmotic volume contraction. 1) The osmolarity of ECF decreases. As a result of the lack of aldosterone in adrenocortical insufficiency, there is decreased NaCl reabsorption, and the kidneys excrete more NaCl than water. 2) ECF volume decreases. Water shifts into the cells because ECF osmolarity decreases; as a result of this shift, ICF osmolarity decreases until it equals ECF osmolarity, and ICF volume increases. 3) Plasma protein concentration increases because of the decrease in ECF volume. Hematocrit increases because of the decreased ECF volume and because the RBCs swell as a result of water entry. 4) Arterial blood pressure decreases because of the decrease in ECF volume.

Answer 115

* Produced by activation of the sympathetic nervous system and angiotensin II. * At low concentrations, angiotensin II preferentially constricts efferent arterioles, thereby "protecting" (increasing) the GFR. * Angiotensin-converting enzyme inhibitors dilate efferent arterioles and produce a decrease in GFR; these drugs reduce hyperfiltration and the occurrence of diabetic nephropathy in diabetes mellitus.

Answer 116

Leads to an increase in RBF. Is produced by prostaglandins E2 and I2, bradykinin, nitric oxide, and dopamine.

Answer 117

Causes vasodilation of afferent arterioles and, to a lesser extent, vasoconstriction of efferent arterioles. Overall increases RBF and GFR.

Answer 118

RBF = RPF / (1-Ht) Note that the denominator in this equation, 1 - hematocrit, is the fraction of blood volume occupied by plasma.

Answer 119

TRUE- Those that are freely filtered but not secreted nor reabsorbed (inulin).

Answer 120

o weak acids have an HA form and an A- form. o The HA form, which is uncharged and lipid soluble, can "back-diffuse" from urine to blood. o The A- form, which is charged and not lipid soluble, cannot back-diffuse. o At acidic urine pH, the HA form predominates, there is more back-diffusion, and there is decreased excretion of the weak acid. o At alkaline urine pH, the A- form predominates, there is less back-diffusion, and there is increased excretion of the weak acid. For example, the excretion of salicylic acid (a weak acid) can be increased by alkalinizing the urine.

Answer 121

o Weak bases have a BH+ form and a B form . o The B form, which is uncharged and lipid soluble, can "back-diffuse" from urine to blood. o The BH+ form, which is charged and not lipid soluble, cannot back-diffuse. o At acidic urine pH, the BH+ form predominates, there is less back-diffusion, and there is increased excretion of the weak base. For example, the excretion of morphine (a weak base) can be increased by acidifying the urine. o At alkaline urine pH, the B form predominates, there is more back-diffusion, and there is decreased excretion of the weak base.

Answer 122

- Tubular fluid (TF) is urine at any point along the nephron. - Plasma (P) is systemic plasma. It is considered to be constant. TF/Px ratio compares the concentration of a substance in tubular fluid at any point along the nephron with the concentration in plasma. a. If TF/P= 1.0, then either there has been no reabsorption of the substance or reabsorption of the substance has been exactly proportional to the reabsorption of water. For example, if TF/PN/ = 1.0, the [Na+] in tubular fluid is identical to the [Na+] in plasma. For any freely filtered substance, TF/P = 1.0 in Bowman space (before any reabsorption or secretion has taken place to modify the tubular fluid). b. If TF/P < 1.0, then reabsorption of the substance has been greater than the reabsorption of water and the concentration in tubular fluid is less than that in plasma. For example, if TF/PNa+ = 8.0, then the [Na+] in tubular fluid is 80% of the [Na+] in plasma. c. If TF/P >1.0, then either reabsorption of the substance has been less than the reabsorption of water or there has been secretion of the substance.

Answer 123

o Maintains constant fractional reabsorption (two-thirds, or 67%) of the filtered Na+ and H20. 1) For example, if GFR spontaneously increases, the filtered load of Na+ also increases. Without a change in reabsorption, this increase in GFR would lead to increased Na+ excretion. 2) However, glomerulotubular balance functions such that Na+ reabsorption also will increase, ensuring that a constant fraction is reabsorbed. 3) The mechanism of glomerulotubular balance is based on Starling forces in the peritubular capillaries, which alter the reabsorption of Na+ and H20 in the proximal tubule. 4) The route of isosmotic fluid reabsorption is from the lumen, to the proximal tubule cell, to the lateral intercellular space, and then to the peritubular capillary blood. 5) Starling forces in the peritubular capillary blood govern how much of this isosmotic fluid will be reabsorbed. 6) Fluid reabsorption is increased by increases in oncotic pressure of the peritubular capillary blood and decreased by decreases in oncotic pressure. 7) Increases in GFR and filtration fraction cause the protein concentration and oncotic pressure of peritubular capillary blood to increase. This increase, in turn, produces an increase in fluid reabsorption. Thus, there is matching of filtration and reabsorption, or glomerulotubular balance.

Answer 124

1) ECF volume contraction increases reabsorption. Volume contraction increases peritubular capillary protein concentration and oncotic pressure, and decreases peritubular capillary hydrostatic pressure. Together, these changes in Starling forces in peritubular capillary blood cause an increase in proximal tubular reabsorption. 2) ECF volume expansion decreases reabsorption. Volume expansion decreases peritubular capillary protein concentration and oncotic pressure and increases hydrostatic pressure Together, these changes in Starling forces in peritubular capillary blood cause a decrease in proximal tubular reabsorption.

Answer 125

o K+ is filtered, reabsorbed, and secreted by the nephron. o K+ balance is achieved when urinary excretion of r exactly equals intake of K in the diet. o K+ excretion can vary widely from 1% to 110% of the filtered load, depending on dietary K+ intake, aldosterone levels, and acid-base status.

Answer 126

1) Glomerular capillaries -filtration occurs freely across the glomerular capillaries. Therefore, TF/P of K in Bowman space is 1.0. 2) Proximal tubule reabsorbs 67% of the filtered K+ along with Na+ and H20. 3) Thick ascending limb of the loop of Henle reabsorbs 20% of the filtered K+. Reabsorption involves the Na+-K+-2cl- cotransporter in the luminal membrane of cells in the thick ascending limb. 4) Distal tubule and collecting duct either reabsorb or secrete K+, depending on dietary K+ intake. o Reabsorption of K involves an H+ / K+ -ATPase in the luminal membrane of the intercalated A cells. Occurs only on a low-K+ diet (K+ depletion). Under these conditions, K+ excretion can be as low as 1% of the filtered load because the kidney conserves as much K+ as possible. o Secretion of K+ occurs in the principal cells. Is variable and accounts for the wide range of urinary K+ excretion. Depends on factors such as dietary K+, aldosterone levels, acid-base status, and urine flow rate.

Answer 127

FALSE - causes HYPOkalemia

Answer 128

o They increase K+ secretion. o Loop and thiazide diuretics that increase flow rate through the late distal tubule and collecting ducts cause dilution of the luminal K+ concentration, increasing the driving force for K+ secretion. o Loop and thiazide diuretics also increase Na+ delivery to the late distal tubule and collecting ducts, which leads to increased Na+ entry across the luminal membrane of principle cells, increased Na+ pumping out of the cells by the Na+-K+ pump, increased intracellular K+ concentration, and increased driving force for K+ secretion. o Also, as a result of increased K+ secretion, these diuretics cause hypokalemia.

Answer 129

o Decrease K+ secretion. If used alone, they cause hyperkalemia. o Spironolactone is an antagonist of aldosterone; triamterene and amiloride act directly on the principal cells. o The most important use of the K-sparing diuretics is in combination with thiazide or loop diuretics to offset (reduce) urinary K losses.

Answer 130

o Urea is reabsorbed and secreted in the nephron by diffusion, either simple or facilitated, depending on the segment of the nephron. o Fifty percent of the filtered urea is reabsorbed in the proximal tubule by simple diffusion. o Urea is secreted into the thin descending limb of the loop of Henle by simple diffusion (from the high concentration of urea in the medullary interstitial fluid). o The distal tubule, cortical collecting ducts, and outer medullary collecting ducts are impermeable to urea; thus, no urea is reabsorbed by these segments. o ADH stimulates a facilitated diffusion transporter for urea in the inner medullary collecting ducts. In the presence of ADH, urea reabsorption from inner medullary collecting ducts contributes to urea recycling in the inner medulla and to the addition of urea to the corticopapillary osmotic gradient. o Urea excretion varies with urine flow rate. At high levels of water reabsorption (low urine flow rate), there is greater urea reabsorption and decreased urea excretion. At low levels of water reabsorption (high urine flow rate), there is less urea reabsorption and increased urea excretion.

Answer 131

o Eighty-five percent of the filtered phosphate is reabsorbed in the proximal tubule by Na+- phosphate cotransport. Because distal segments of the nephron do not reabsorb phosphate, 15% of the filtered load is excreted in urine. o Parathyroid hormone (PTH) inhibits phosphate reabsorption in the early proximal tubule by activating adenylate cyclase, generating cAMP, and inhibiting Na+-phosphate cotransport. Therefore, PTH causes phosphaturia and increased urinary cAMP. o Phosphate is a urinary buffer for H+; excretion of H2P04- is called titratable acid. o Fibroblast growth factor (FGF23), which is secreted by bone, inhibits Na+-phosphate cotransport in the early proximal tubule.

Answer 132

o 60% of the plasma Ca2+ is filtered across the glomerular capillaries. o Together, the proximal tubule and thick ascending limb reabsorb more than 90% of the filtered Ca2+by passive processes that are coupled to Na+ reabsorption. o Loop diuretics (e.g., furosemide) cause increased urinary Ca2+ excretion. Because Ca2+ reabsorption is driven by the lumen-positive potential difference in the loop of Henle, inhibiting the Na+-zCI--K+ cotransporter reabsorption with a loop diuretic inhibits the lumen-positive potential difference and thereby inhibits Ca2+reabsorption. If volume is replaced, loop diuretics can be used in the treatment of hypercalcemia. o Together, the distal tubule and collecting duct reabsorb 8% of the filtered Ca2 + by an active process, based on hormonal signals -> PTH increases Ca2+reabsorption by activating adenylate cyclase in the distal tubule. o Thiazide diuretics increase Ca2+ reabsorption in the early distal tubule and therefore decrease Ca2+excretion. For this reason, thiazides are used in the treatment of idiopathic hypercalciuria.

Answer 133

o It is reabsorbed in the proximal tubule, thick ascending limb of the loop of Henle, and distal tubule. o In the thick ascending limb, Mg2+ and Ca2+compete for reabsorption; therefore, hypercal- cemia causes an increase in Mg2+ excretion (by inhibiting Mg2+ reabsorption). o Likewise, hypermagnesemia causes an increase in Ca2+ excretion (by inhibiting Ca2+ reabsorption).

Answer 134

It is also called hyperosmotic urine, in which urine osmolarity > blood osmolarity.

Answer 135

When circulating ADH levels are high (e.g., water deprivation, volume depletion, SIADH)

Answer 136

o Is the gradient of osmolarity from the cortex (300 mOsm/L) to the papilla (1200 mOsm/L) and is composed primarily of NaCl and urea. o Is established by countercurrent multiplication in the loops of Henle and urea recycling in the inner medullary collecting ducts. o Is maintained by countercurrent exchange in the vasa recta.

Answer 137

o Depends on NaCI reabsorption in the thick ascending limb and countercurrent flow in the descending and ascending limbs of the loop of Henle. o Is augmented by ADH, which stimulates NaCl reabsorption in the thick ascending limb. Therefore, the presence of ADH increases the size of the corticopapillary osmotic gradient.

Answer 138

o Urea recycling from the inner medullary collecting ducts into the medullary interstitial fluid also is augmented byADH (by stimulating the UT1 transporter). o Vasa recta are the capillaries that supply the loop of Henle. They maintain the corti- copapillary gradient by serving as osmotic exchangers. Vasa recta blood equilibrates osmotically with the interstitial fluid of the medulla and papilla.

Answer 139

o The osmolarityof the glomerular filtrate is identical to that of plasma (300 mOsm/L). o Two-thirds of the filtered H20 is reabsorbed isosmotically (with Na+, a-, HC03-, glucose, amino acids, and so forth) in the proximal tubule. o TF/Posm = 1.0 throughout the proximal tubule because H20 is reabsorbed isosmotically with solute.

Answer 140

o It is also called the diluting segment. o Reabsorbs NaCl by the Na+/K+/2CI- cotransporter o Is impermeable to H20. Therefore, H20 is not reabsorbed with NaCl, and the tubular fluid becomes dilute. o The fluid that leaves the thick ascending limb has an osmolarity of 100 mOsm/L and TF/Posm <1.0 as a result of the dilution process.

Answer 141

o It is called the cortical diluting segment. o Like the thick ascending limb, the early distal tubule reabsorbs Na Cl but is impermeable to water. Consequently, tubular fluid is further diluted.

Answer 142

o ADH increases the H2O permeability of the principal cells of the distal tubule. o H2O is reabsorbed from the tubule until the osmolarity of distal tubular fluid equals that of the surrounding interstitial fluid in the renal cortex (300mOsm/L) o TF/Posm = 1.0 at the end of the distal tubule because osmotic equilibration occurs in the presence of ADH.

Answer 143

o As in the late DT, ADH increases H2O permeability of the principal cells of the collecting ducts. o As tubular fluid flows through the collecting ducts, it passes through the corticopapillary gradient (regions of increasingly higher osmolarity), which was previously established by countercurrent multiplication and urea recycling. o H20 is reabsorbed from the collecting ducts until the osmolarity of tubular fluid equals that of the surrounding interstitial fluid. o The osmolarity of the final urine equals that at the bend of the loop of Henle and the tip of the papilla (1200 mOsm/L). o TF/Posm >1.0 because osmotic equilibration occurs with the corticopapillary gradient in the presence of ADH.

Answer 144

o Is called hyposmotic urine, in which urine osmolarity < blood osmolarity. o Is produced when circulating levels of ADH are low (e.g., water intake, central diabetes insipidus) or when ADH is ineffective (nephrogenic DI).

Answer 145

1) Corticopapillary osmotic gradient -> no ADH. Is smaller than in the presence of ADH because ADH stimulates both countercurrent multiplication and urea recycling. 2) Proximal tubule--no ADH. As in the presence of ADH, two-thirds of the filtered water is reabsorbed isosmotically. TF/Posm =1.0 throughout the proximal tubule. 3) Thick ascending limb of the LOH - no ADH. As in the presence of ADH, NaCl is reabsorbed without water, and the tubular fluid becomes dilute (although not quite as dilute as in the presence of ADH). TF/Posm< 1.0. 4) Early DT -> no ADH. As in the presence of ADH, NaCl is reabsorbed without H20 and the tubular fluid is further diluted. TF/Posm < 1.0. 5) Late distal tubule and collecting ducts -> no ADH. In the absence ofADH, the cells of the late distal tubule and collecting ducts are impermeable to H20. Thus, even though the tubular fluid flows through the corticopapillary osmotic gradient, osmotic equilibration does not occur. 6) The osmolarity of the final urine will be dilute with an osmolarity as low as 50m0sm/L. TF/Posm< 1.0.

Answer 146

o It is used to estimate the ability to concentrate or dilute the urine. o Free water, or solute-free water, is produced in the diluting segments of the kidney {i.e., thick ascending limb and early distal tubule), where NaCl is reabsorbed and free water is left behind in the tubular fluid. o In the absence of ADH, this solute-free water is excreted and CH20 is positive. o In the presence of ADH, this solute-free water is not excreted but is reabsorbed by the late distal tubule and collecting ducts and CH2O is negative.

Answer 147

FALSE - it is positive. CH2O will be positive with hyperosmotic urine.

Answer 148

Two: volatile and nonvolatile acids

Answer 149

o C02, produced from the aerobic metabolism of cells. o C02 combines with H20 to form the weak acid H2C03, which dissociates into H+ and HC03- by the following reactions: C02 + H20 <--> H2C03 <--> H+ + HCO3- o Carbonic anhydrase, which is present in most cells, catalyzes the reversible reaction between C02 and H20.

Answer 150

o They are also called fixed acids o Include sulfuric acid (a product of protein catabolism) and phosphoric acid (a product of phospholipid catabolism). o They are normally produced at a rate of 40 to 60mmoles/d. o Other fixed acids that may be overproduced in disease include ketoacids and lactic acid., or may be ingested including salicylic acid, formic acid (methanol poisoning), and oxalic and glycolic acids (ethylene glycol poisoning).

Answer 151

o Substance that can prevent a change in pH when H+ ions are added or removed to/from a solution. o Normally it consist of a weak acid and its conjugate base, or a weak base and its conjugated acid. o Are most effective within 1.0pH unit of the pK of the buffer.

Answer 152

Extracellular buffers and intracellular buffers

Answer 153

o The major extracellular buffer is HCO3- which is produced from C02 and H20. The pK of the C02/HC03- buffer pair is6.1. o Phosphate is a minor extracellular buffer. The pK of the H2P04- / HPO4-2 buffer pair is 6.8. Phosphate is most important as a urinary buffer; excretion of H+ as H2P04- is called titratable acid.

Answer 154

o Organic phosphates (e.g., AMP, ADP, ATP, 2,3-DPG) o Proteins * Imidazole and alpha-amino groups on proteins have pKs that are within the physiologic pH range. * Hemoglobin is a major intracellular buffer. * In a physiologic pH range, deoxyhemoglobin is a better buffer than oxyhemoglobin.

Answer 155

- RIFLE -> Risk Injury Failure End Stage Kidney Disease - AKIN -> Acute Kidney Injury Network

Answer 156

In stable patients - in steady state conditions, not in hypotensive or unstable patients.

Answer 157

Kidney Disease Improving Global Outcomes initiative

Answer 158

o Increase in serum creatinine by >0.3mg/dL within 48h OR o Increase in serum creatinine > 1.5 x baseline OR o Urine production < 0.5mL/kg/h (6h)

Answer 159

o It is a functional marker, not a biomarker o Patients with either pre-renal or intrinsic AKI, they will have larges decreases in GFR but creatinine will change very little -> can lose more than 50-60% of the functional renal capacity and still be non azotemic -> prevents early recognition if we only rely on creatinine. o Once the patient becomes azotemic, then there will be probably very little changes in GFR and creatinine changes are larger (can be very large and GFR not change that much on late phases of AKI)

Answer 160

o Easy and simple to measure o Consistent repetitive measurement o Threshold values well documented and validated o Correlate with the presence of illness and its severity o Reasonable cost o Measurable in biological fluids

Answer 161

FALSE - it has been looked at in AKI and CKD patients. o It is based on function and not ongoing damage -> both AKI and CKD have decreased renal function. o As seen in the graph, no difference between levels of SDMA in patients with AKI compared to CKD. o Then SDMA does not seem very useful in the critical care setting -> first, in an azotemic patient, SDMA will be elevated but not give an answer on the pathology or etiology. Second, studies show that patients with AKI and azotemic, SDMA remains normal. o It is important in stable patients when trying to recognize early CKD - prep, geriatric.

Answer 162

o Based on function, not on tubular cell damage. o Useful, but like many other functional markers (like SDMA), once patient is azotemic then they are not useful. o In nonazotemic or in hospital AKI it has not been validated.

Answer 163

o There is a significant difference in plasma NGAL in dogs with AKI compared with CKD dogs

Answer 164

o Urine NGAL to creatinine ration (UNCR) increases around day 11 or so and peaks around day 17-18 o Plasma creatinine has a delay of 4-5 days in becoming elevated, and the peak is also delayed compared to NGAL. o Also important during recovery - identifying patients that are responding to therapy or not

Answer 165

o Urinary microscopy is important!!! -> presence of epithelial cells, casts o Other biomarkers might not be available and when we have a patient with a urinary catheter, we do not have to forget to assess urine microscopy as it can be very valuable.

Answer 166

Tachycardia, hypotension and shock index Also, number of vials of antivenom, vials of antivenom/kg and receiving pRBCs.

Answer 167

Blood flow redistribution Capillary recruitment Ischemia: GI, kidneys, lungs Dysoxia - abnormal tissue oxygen metabolism * Lactate production * Metabolic acidosis * Na/K ATPase pump dysfunction * Cytotoxic edema * Increased Ca2+ * Cell death

Answer 168

o Alcohol dehydrogenase o The therapeutic options to prevent AKI are directed toward blocking that enzyme - ethanol, fomepizole -> will be changing the rate of conversion of ethylene glycol to glycoaldehyde

Answer 169

RBCs destruction -> hemolysis -> hemoglobinuria

Answer 170

o One of the most common causes of AKI o Probably community acquired AKI - patients will come with azotemia already. o Some causes: pyelonephritis, leptospirosis, granulomatous disease (systemic aspergillosis), neoplasia (lymphoma)

Answer 171

o Witness leptospirosis test (remember PCR is not a serologic test!!) o Based in IgM levels that raise early in acute phase compared to IgG levels measured by common micro agglutination tests. o Superior in recognizing clinical disease in the first 14 days of the infection o After those 14 days, IgM tend to decrease and IgG starts to increase.

Answer 172

o Obstructive diseases: urolithiasis, neoplasia, prostatic disease, FLUTD o Uroabdomen o Vital early intervention, surgical disease.

Answer 173

IRIS stage I-III -> more than 900 days IRIS stage IV-V -> less than 600 days o Early treatment has a great MST!

Answer 174

o Nephrotoxic medications o Uncorrected cardiovascular shock o Fluid overload

Answer 175

Because of the tubuloglomerular feedback -> high concentrations of Cl will reach the macula densa -> vasoconstriction -> decreases GFR

Answer 176

Renal tubular vacuolization

Answer 177

FALSE - it develops after visceral edema

Answer 178

o Level 0: <1.6mg/dL and change <0.3mg/dL o Level 1: <1.6mg/dL and change >0.3mg/dL o Level 2: >1.6mg/dL and change >0.3mg/dL

Answer 179

o Simple uncomplicated UTI is a sporadic bacterial infection of the bladder in an otherwise healthy individual with normal urinary tract anatomy and function. o Clinical signs are nonspecific and should not be used alone for diagnosis of UTI. o Aerobic bacterial culture and susceptibility testing should be performed in all cases, to confirm the presence of infection, identify the presence of resistant bacteria, to help differentiate reinfection from relapse, and to provide the clinician with guidance. o Cystocentesis should be used for sample collection. Catheterized samples can be evaluated for culture but cystocentesis samples are preferred. Free-catch (midstream voiding or manual expression) samples should not be used. o It is imperative that a quantitative culture be performed. o Urine samples for culture and susceptibility testing should be refrigerated immediately after collection and submitted to the laboratory asap. Results of samples that take 24 hours or more to reach the laboratory should be interpreted with caution because of the potential for both false positive and false negative results o For samples collected by cystocentesis, any level of bacterial growth may be significant, although samples from a UTI typically contain ≥10^3 colony forming units (CFU)/mL o For samples collected via catheter, bacterial counts ≥10^4 CFU/mL in males and ≥10^5 in females are typically considered significant.

Answer 180

o Antimicrobial therapy is indicated in most cases while awaiting culture and susceptibility results to relieve patient discomfort. o In most situations, initial therapy should consist of amoxicillin (11– 15 mg/kg PO q8h) or trimethoprim-sulfonamide (15 mg/kg PO q12h). o Amoxicillin/clavulanic acid (12.5–25mg/kg PO q8h) is an acceptable option but is not recommended initially because of the lack of evidence regarding the need for clavulanic acid and the desire to use the narrowest spectrum that is possible while maintaining optimal efficacy. o If culture and susceptibility testing indicates the presence of an isolate that is resistant in vitro but there has been apparent clinical response, maintaining the current treatment is acceptable provided a follow-up urinalysis, including culture, is performed after treatment has been completed to ensure resolution of infection. o If culture and susceptibility data indicate that the isolate is not susceptible to the chosen antimicrobial and there is a lack of clinical response, then therapy with the original drug should be discontinued and treatment with an alter- native drug begun. o Adequate evidence regarding duration of treatment is lacking, precluding the ability to make a specific recom- mendation for treatment duration. Typically, uncomplicated UTIs are treated for 7–14 days. Shorter treatment time (≤7 days) may be effective. o There is no indication for measures beyond monitoring of clinical signs.

Answer 181

o A complicated UTI is an infection that occurs in the presence of an anatomic or functional abnormality or a comorbidity that predisposes the patient to persistent infection, recurrent infection, or treatment failure. o In humans, the concurrent presence of prostatitis, urinary calculi, a neurogenic bladder, pregnancy, diabetes mellitus, or immunocompromising disorders also defines a complicated UTI. it is reasonable to apply this to companion animals. o Recurrent UTIs, as defined by the presence of 3 or more episodes of UTI during a 12-month period also indicate complicated infection. o Reinfection is recurrence of a UTI within 6 months of cessation of previous, apparently successful treatment and isolation of a different microorganism. o Relapse is recurrence of a UTI within 6 months of cessation of previous, apparently successful treatment and isolation of an indistinguishable organism from the one that was present previously, which is presumably because of failure to completely eliminate the pathogen. o A refractory infection is similar to a relapse except that it is characterized by persistently positive results using culture during treatment (despite in vitro susceptibility to the antimicrobial), with no period of eliminated of bacteriuria during or after treatment.

Answer 182

o General principles of diagnosis for simple uncomplicated UTI, apply for complicated UTIs. o A diagnosis of recurrent UTI should never be based on clinical signs or urine sediment examination alone. Bacterial culture and susceptibility testing should be performed in all instances to confirm recurrent UTI. o Determine any underlying factors that could be associated with recurrence or relapse. A CBC/chem, UA, imaging and, if deemed appropriate, endocrine testing should be performed. A complete PE, including rectal palpation and examination of the vulva is required. o If cystotomy is being performed, culture of a bladder wall biopsy as well as any uroliths that might be present is recommended.

Answer 183

o If the clinical condition of the patient permits, consideration should be given to waiting for culture results before starting therapy. o If treatment must be initiated immediately, a drug should be selected from those recommended for initial treatment of simple uncomplicated UTI. o Where possible, the drug class used should be different from that used to treat the prior UTI(s) (i.e., if amoxicillin was used initially, start treatment with trimethoprim-sulfadiazine). o After treatment has been initiated, continued treatment should be based on the results of culture and susceptibility testing. Preference should be given to drugs that are excreted in urine predominantly in an active form. o If more than one bacterial species is identified on initial culture, the relevance of the each organism should be considered, based on the bacterial counts and the pathogenicity of the organisms. o When present in a mixed infection, anecdotal evidence suggests that infection by Enterococcus spp. will often resolve when the other organism is successfully treated. o Ideally, antimicrobial therapy should be directed against both organisms. In some instances, an antimicrobial effective against both organisms will not be available. Combination therapy that would be potentially effective against both organisms should be considered

Answer 184

o There is no supporting evidence for administration of other drugs (e.g., clarithromycin) for the purpose of breaking down bacterial biofilm. o There is no supporting evidence that direct instillation of antimicrobials, antiseptics, or DMSO directly into the bladder via a urinary catheter is effective for treatment of recurrent UTIs. These compounds are quickly flushed out of the bladder when the animal urinates and may be locally irritating. o Any underlying causes should be managed appropriately, whenever possible. o Evidence supporting the duration of therapy for complicated UTI does not exist. Typically, 4 weeks of treatment has been recommended.

Answer 185

o Urine culture should be considered 5–7 days after initiation of therapy, particularly in patients with a history of relapsing or refractory infection, or those considered at high risk for ascending or systemic infection. o Any bacterial growth during treatment indicates potential treatment failure and should prompt immediate reevaluation. o Urine culture is recommended 7 days after cessation of therapy in all cases. o Although there is some evidence for a benefit of nutritional supplements (e.g., cranberry juice extract) for this indication in humans, the evidence is not strong and some studies have shown no effect in dogs and cats.

Answer 186

o Subclinical bacteriuria is the presence of bacteria in the urine as determined by positive bacterial culture, in the absence of clinical and cytological evidence of UTI. o Treatment may not be necessary in animals that have no clinical signs of UTI and no evidence of UTI based on examination of urine sediment. o Treatment may be considered if there is concern that there is a particularly high risk of ascending or systemic infection (e.g., immunocompromised patients, patients with underlying renal disease). o The presence of multidrug-resistant bacterium does not represent, by itself, an indication for treatment. o Anecdotal information suggests that multidrug-resistant organisms will sometimes be replaced with susceptible organisms if treatment is withheld -> then treatment with routine antimicrobials may be more practical if decolonization is desired or if clinical disease develops.

Answer 187

o UTI and subclinical bacterial colonization of the bladder are commonly identified in dogs with indwelling urinary catheters. o Animals with u-caths and no clinical sx of infection -> culture for diagnosis of the presence of bacteria in urine is not recommended in the absence of clinical signs consistent with an active infection. o It is not necessary to treat catheterized animals with bacteriuria in the absence of clinical or cytological evidence supporting the presence of an infection. o Prophylactic antimicrobial therapy for prevention of UTI in catheterized animals is never indicated. o When u-cath is being removed -> no evidence supporting the need to culture the catheter tip at time of catheter removal since catheter tip culture results are not predictive of development of catheter-associated UTI. o No evidence supporting routine culture of urine after catheter removal. However, culture of the urine (ideally collected by cystocentesis after catheter removal) may be reasonable in patients in which the risk and implications of UTI are high (e.g., recently obstructed male cat with at high risk for reobstruction). o Clinical monitoring and cytological examination to detect a potential UTI are preferred to urine culture in a patient with no signs of UTI. o There is no indication for routine (prophylactic) antimicrobial treatment following urinary catheter removal in an animal with no clinical or cytological evidence of active UTI

Answer 188

o Suspect UTI if u-cath + clinical signs. o Infection should be suspected in all cases of fever of unknown origin or bacteremia with an unknown focus. Infection should also be suspected when there are gross or cytological (i.e., hematuria, pyuria) abnormalities. o Urine culture should always be performed if infection is suspected. o If a catheter must remain in place and signs of UTI are present, the catheter should be replaced and a urine sample collected through the new catheter for culture. Several mL of urine should be withdrawn to clear the catheter and discarded prior to obtaining the sample for culture. o When possible, catheters should be removed and urine sampled by cystocentesis after an appropriate period of time has passed for the bladder to fill with urine. o Urine culture should never be performed from the collection bag. o Treatment is more likely to be successful if the catheter can be removed.

Answer 189

o Treatment should be initiated immediately, while awaiting culture and susceptibility results. o Initial treatment should involve antimicrobial drugs known to have local or regional efficacy against Gram-negative Enterobacteriaceae, based on the predominance of those organisms in pyelonephritis. o If regional data are supportive, treatment with a fluoroquinolone excreted in urine in the active form is a reasonable first choice. o If ascending infection is suspected, urine culture results obtained for diagnosis of lower UTI might be the basis of initial therapy. o If the upper UTI results from hematogenous spread, initial therapy should be based on cultures of blood or the infected site, whenever available. o Treatment of 4–6 weeks is often recommended. A shorter duration might be effective; however there is currently inadequate evidence to provide objective recommendations. o UA and culture should be performed 1 week from the start of treatment because of potential severity of disease and long treatment duration. If the same organism is isolated, one should consider adding an antimicrobial to which the organism is susceptible in vitro, if possible. o Culture is recommended 1 week after cessation of therapy to ensure elimination of infection.

Answer 190

o Multidrug-resistant pathogens, including various Enterobacteriaceae, staphylococci, and enterococci, are becoming increasingly problematic. The use of drugs such as vancomycin, carbapenems, and linezolid is not justified unless the following criteria are met: 1) Infection must be documented based on clinical, culture, and cytological abnormalities. The use of these drugs for the treatment of subclinical infection is not supported. 2) Resistance to all other reasonable options and susceptibility to the chosen antimicrobial must be documented. 3) The infection must be potentially treatable. The use of critical drugs in situations where there is little realistic chance of elimination of infection (e.g., failure to remove the underlying cause) is not supported. 4) Consultation with someone with expertise in infectious diseases and antimicrobial therapy must be obtained to determine whether there are any other viable options and whether treatment is reasonable.

Answer 191

o Renal replacement o Therapeutic plasma exchange o Hemoperfusion

Answer 192

Diffusion Convection Ultrafiltration Adsorption * Metabolism of the substance -> provided by the patient.

Answer 193

The movement of particles from an area of higher concentration to an area of lower concentration?

Answer 194

FALSE - the HIGHER the concentration gradient, the faster the rate of diffusion

Answer 195

In one side is blood, in the other side is dialysate.

Answer 196

300-800mL/min (average of 500mL/min)

Answer 197

o Involves installation of a discrete volume of dialysate that is periodically removed and replaced with fresh dialysate. o During the dwell time, diffusion occurs -> short dwell times (1-2h) used in AKI do not allow complete equilibrium - frequent exchanges increase the overall uremic toxin removal.

Answer 198

Ultrafiltration

Answer 199

o It involves a hydrostatic pressure gradient to cause water movement. o By creating negative pressure on the side opposite to the blood compartment, water is "pulled" out of the blood.

Answer 200

o Number of mL of fluid transferred across the membrane per hour when 1mmHg of transmembrane pressure is applied. o With a higher KUF, less of a pressure gradient is needed to remove fluid.

Answer 201

It removes solutes by removing the water in which they are dissolved - aka "solute drag"

Answer 202

RRT = Renal Replacement Therapy Extracorporeal form of therapy that replaces the non-endocrine function of the kidneys • Excretion of uremic waste products • Restoration of acid-base balance • Restoration of body water balance

Answer 203

o The semipermeable membrane has larger pores that allow plasma proteins (immunoglobulins) to be removed, leaving behind the cellular component. o Since plasma is being removed, part of the replacement fluid is typically FFP, although part may be other colloids or crystalloid fluids.

Answer 204

o Certain substances, like cytokines, will bind to the dialyzer membrane and therefore, they can be removed from the circulation. o The adsorptive capacity of the dialysis membrane is limited -> ineffective method of removal. o Charcoal and other hemoperfusion techniques are better suited for significant adsorption.

Answer 205

o In removing substances that have significant protein binding. o The unbound portion of the substance will bind to the carbon, and a small amount of the substance will dissociate from protein, making it available to bind to the carbon. o Carbon cartridges become saturated with the substance within several hours -> the exact time will depend on the concentration of the substance and the amount of charcoal.

Answer 206

o The % of a substance removed in a single pass through the dialyzer or divide. o Measured by sampling the blood entering and the blood exiting the device o Formula => (Con in - Con ou) / Con in Con = concentration

Answer 207

o Volume of blood completely cleared of a certain solute during a single pass through the device (same concept as renal clearance). o Clearance = Qb x ((Con in - Con out)/Con in) Qb => flow rate o Units: mL/min

Answer 208

o At slower blood flow rates, the blood may be completely cleared of small solutes such as urea in one pass through the dialyzer (100% extraction), in which case the blood flow rate approximates clearance. o At fast blood flow rates relative to the dialysate rate, the blood may not reach equilibrium and the extraction rate will be lower.

Answer 209

Clearance = Jf x Cs x S Jf = amount of ultrafiltration Cs = concentration of solute S = sieving coeficient.

Answer 210

FALSE - a sieving coeficient of 1 means the solute freely passes through the membrane. A sieving coeficient of 0 means the solute does not get filtered at all.

Answer 211

Urea reduction ratio (URR)

Answer 212

URR = (BUNpre - BUNpost) / BUNpre

Answer 213

To remove immunoglobulins.

Answer 214

o 63% O if we remove 1.5 x the plasma volume -> 78%

Answer 215

Dog - 290-310mOsm/kg Cat - 308-335mOsmo/kg

Answer 216

Maintenance of effective circulating volume

Answer 217

Insertion of aquaporins 2 in the luminal membrane of the principal cells.

Answer 218

o Increase urine production by altering solute reabsorption throughout the nephron. o Water movement is passive -> water will follow the solutes -> increased tubular water content, increased urine volume and decreased ECF volume.

Answer 219

- Dose administered. - The effect of the site of action - The ability of more distal segments to alter the filtrate

Answer 220

TRUE -> Filtrate reabsorption is flow dependent. A diuretic that prevents Na reabsorption in the PT will result in increased Na delivery to the LOH and increased LOH Na reabsorption.

Answer 221

By filtration or secretion, except spironolactone.

Answer 222

o Will block the enzyme CA, decreasing the secretion of H+, increasing Na and HCO3- losses. o Acetozolamide o Limited effect due to increased distal reabsorption - not used to treat edematous conditions. o Frequently used to decrease aqueous humor production in glaucoma patients.

Answer 223

o Found within the PT and allow for the reabsorption across the apical membrane of 1 or 2 Na for each glucose. o SGLT2 are responsible for 80-90% of the glucose reabsorption that occurs in the PT. o In human medicine, SGLT2 inhibitors -> initially used as anti-diabetic drugs to prevent glucose reabsorption. They also induced transient natriuresis and osmotic diuresis. o They have been shown to improve outcome in heart failure patients, regardless of diabetic status.

Answer 224

o Bexagliflozin has been shown to cause 1.5-fold increase in natriuresis in dogs and a 3.7-fold increase in urine volume in a 24h period. o Examples: bexagliflozin, empagliflozin

Answer 225

o NKCC cotransporter in the ascending LOH and macula densa o Compete with chloride for its biding site on the carrier. o When bound by a loop diuretic, the NKCC contransporter is inactive -> urinary loss of Na, K, Cl, Ca, Mg and Ph. o Blockade of the MD carrier may impar normal tubuloglomerular feedback. o Furosemide -> thought to have additional benefits: protection agains ischemic injury, vasodilatory effects and bronchial antispasmodic properties.

Answer 226

o 90-95% protein bound and a weak organic acid -> minimally filtered at the glomerulus. o Secreted via organic acid transporters (OAT) in the proximal tubule. o Only unbound furosemide is available to bind NKCC carrier. o Due to variations in bioavailability -> oral dose up to 5 times higher than IV dose to achieve similar diuresis. o Patients with decreased GFR, kidney dysfunction or hypoalbuminemia -> higher dose might be necessary to reach therapeutic levels due to diminished drug excretion.

Answer 227

o Osmotic diuretic o Non-reabsorbable polysaccharide o After IV injection -> increase in intravascular osmolality -> water will move from intracellular space to intravascular space. o Freely filtered in the glomerulus and prevents reabsorption of water in the PT and LOH. o In patients with increased ICP -> thought to reduce pressure by different mechanisms: * Decreased intracellular water content * Rheologic properties * Acts as free radical scavenger.

Answer 228

Improve GFR, blood flow to the kidneys, tubular flow and reduce absorption of urea and Na.

Answer 229

o Na/Cl cotransporter in the distal tubule o These cotransporters are responsible for 3-8% of Na reabsorption -> less potent than other diuretics. o Secreted via organic acid transporters in the proximal tubule and compete for the chloride binding site on the cotransporter. o Promote Na and Cl loss o In contrast to loop diuretics, they result in Ca retention. o More frequently used in a sequential nephron blockade strategy than as only med. o May decrease urine output in patient with diabetes inspidus -> induce volume depletion -> promote proximal tubular Na reabsorption.

Answer 230

o Release of aldosterone results in increased expression of Na channels on the apical membrane and Na/K ATPase channels on the basolateral membrane of the principal cells, to increase Na reabsorption. o Aldosterone antagonists will competitively antagonize aldosterone receptor in the late distal tubule and collecting duct principal cells, decreasing Na reabsorption. o Can be used in combination with other diuretic drugs or can be the only therapy for hyperaldosteronism. o Associated with minimal potassium wasting and may reduce myocardial remodeling.

Answer 231

o New class of drugs that directly antagonize V2 receptors. o Promote excretion of free water by preventing the insertion of aquaporins in the luminal membrane of principal cells. o In people used in hyponatremic edematous states like CHF or cirrhosis. o Only one case report in vetted in a dog with SIADH.

Answer 232

Hyposmotic volume contraction. The osmolarity of ECF decreases. As a result of the lack of aldosterone in adrenocor- tical insufficiency, there is decreased NaCl reabsorption, and the kidneys excrete more NaCl than water.

Answer 233

Prostaglandins Bradykinin Nitric oxide Dopamine.

Answer 234

Atrial natriuretic peptide (ANP) causes vasodilation of afferent arterioles and, to a lesser extent, vasoconstriction of efferent arterioles; overall, ANP increases RBF and GFR

Answer 235

80 to 180mmHg

Answer 236

o Myogenic mechanism, in which the renal afferent arterioles contract in response to stretch. Thus, increased renal arterial pressure stretches the arterioles, which contract and increase resistance to maintain constant blood flow. o Tubuloglomerular feedback, in which increased renal arterial pressure leads to increased delivery of fluid to the macula densa. The macula densa senses the increased load and causes constriction of the nearby afferent arteriole, increasing resistance to maintain constant blood flow.

Answer 237

In prerenal azotemia {hypovolemia), BUN increases more than serum creatinine (because hypovolemia increases urea reabsorption in proximal tubule) and there is an increased BUN/creatinine ratio (>20:1)

Answer 238

Increases in the filtration fraction produce increases in the protein concentration of per- itubular capillary blood, which leads to increased reabsorption in the proximal tubule. Decreases in the filtration fraction produce decreases in the protein concentration of peritubular capillary blood and decreased reabsorption in the proximal tubule.

Answer 239

The glomerular barrier consists of the capillary endothelium, basement membrane, and filtration slits of the podocytes

Answer 240

8 mm Hg (favoring filtration)

Answer 241

Na+-glucose cotransport in the early proximal tubule reabsorbs glucose from tubular fluid into the blood. There are a limited number of Na+ -glucose transporters. At plasma glucose concentrations less than ~250 mg/ dL, all of the filtered glucose can be reabsorbed because plenty of carriers are available; in this range, the line for reabsorption is the same as that for filtration.

Answer 242

Transport Maximum (Tm) dogs: 180mg/dL cats: 240-290mg/dL

Answer 243

Because is a weak acid, in which the A- form predominates at alkaline urine and there is less back-diffusion from urine to blood.

Answer 244

Spironolactone Triamterene and amiloride

Answer 245

PTH causes phosphaturia and increased urinary cAMP PTH inhibits phosphate reabsorption in the early proximal tubule by activating adenylate cyclase, generating cAMP, and inhibiting Na+ -phosphate cotransport

Answer 246

False - stimulates, it inhibits

Answer 247

Is the gradient of osmolarity from the cortex (300 mOsm/L) to the papilla (1200 mOsm/L) and is composed primarily of NaCl and urea. *established by the countercurrent multiplication in the loops of henle (brings electrolytes into the interstitium) and urea recycling in the innner medullary collecting ducts *maintained by countercurrent exchange in the vasa recta

Answer 248

TRUE - this gradient is augmented by ADH, which stimulates NaCl reabsorption in the thick ascending limb. Therefore, the presence of ADH increases the size of the corticopapillary osmotic gradient.

Answer 249

thick ascendinc limb of henle early distal convoluted tubule

Answer 250

Dogs = 3-5ml/kg/min Cats = 2.5-3.5ml/kg/min

Answer 251

90% cortex 10% outer medulla 2-3% inner medulla

Answer 252

Thick ascending limb of henle at its junction with the distal convoluted tubule

Answer 253

Presence of ADH Hyperosmotic renal medullary interstitium

Answer 254

In human medicine, 2 classification systems recently have been validated that use evidence of AKI to predict outcome in patients in the critical care setting. *RIFLE (R-risk, I-injury, F-failure, L-loss, and E-end stage kidney disease) * AKIN (Acute Kidney Injury Network) They have been compared in human literature and show no statistical difference in predicting mortality.

Answer 255

1. The initiation phase * The initiation phase occurs when renal blood flow decreases, resulting in cellular ATP depletion and subsequent tubular epithelial cell injury. These changes alter the ability of tubular epithelial cells and vascular endothelial cells to maintain normal renal function (reabsorption and secretion), as well as up-regulate a variety of chemokines and cytokines to initiate an inflammatory cascade. Intervention at this phase may prevent progression to more severe injury, but injury at this stage occurs on a subcellular level and may not be biochemically evident. 2. Extension phase - continued hypoxia following the initial ischemic event and an inflammatory response, most prominent in the outer medullary region of the kidney. During this phase, vascular endothelial damage likely plays a key role in the continued ischemia of the tubular epithelium, as well as the inflammatory response. Cells in the outer medullary region undergo injury and death via necrosis and apoptosis. The cellular injury in this region leads to the continual reduction in GFR, whereas cells of the proximal tubule in the outer cortex, where blood flow has returned, undergo cellular repair and improve morphologically • biochemical derangements and clinical manifestations of disease manifest 3. Maintenance phase -cell death and regeneration occur simultaneously --> consists of cells undergoing repair, migration, apoptosis, and proliferation to reestablish and maintain cellular and tubular integrity. The GFR usually remains stable at the level determined by the severity of the initial event. Cellular repair and reorganization results in slowly improving cellular function, setting the stage for improvement in organ function. Blood flow returns toward normal and epithelial cells establish intracellular and intercellular homeostasis. Removal of the initiating cause at this stage does not alter the existing damage but may allow for the balance to shift in favor of parenchymal regeneration 4. The recovery phase. Improvement in GFR and tubular function; this final phase may last weeks to months * cellular differentiation continues, epithelial polarity is re-established, and normal cellular and organ function returns. Alternatively, renal repair can be maladaptive with inflammation, fibrosis, and vascular rarefaction leading to persistent cell and tissue malfunction and eventually CKD

Answer 256

Between initiation and the extension phase

Answer 257

• Functional markers (indicates decrease global kidney function mass due to kidney cell damage): creat, urea, SDMA, UO • Biomarkers (Active Injury Markers - more useful for ongoing active injury without loss of functional kidney mass), but also helpful to localize where the injury is coming from.: NGAL, Cystatin C, Kim-1; Clusterin, NAG, IL-18 alfa-1/beta2, microglobulins"

Answer 258

Renal tubular vacuolization (RTV)= For every 1ml/kg increase in 6% colloids - 1.6% increased chances of having severe RTV

Answer 259

"** GFR ** Fractional clearance (FC) of solutes Which are based on timed collections of urine, but these methods are time-consuming, require placement of a urinary catheter, and are cumbersome to perform"

Answer 260

*Increased GFR, urine production, and decreased FC of Na were markers of renal recovery. * The changes in FCNa and ERNa occurred in surviving dogs before any evidence of resolution of their azotemia or dialysis dependency The FC of Na is a simple, noninvasive, and cost-effective method that can be used to evaluate recovery of renal function

Answer 261

Cystatin C is a low-molecular-weight protein produced at a constant rate in all nucleated cells and excreted exclusively by the kidneys.- its role --> inhibiting lysosomal proteases from diseased or ruptured cells, protecting the connective tissue

Answer 262

TRUE --> Based on this paper:

Answer 263

"findings of our study do not support an association between HES and AKI in dogs. This is consistent with previous experimental models of acute hemorrhage in dogs The proposed mechanism of HES-induced AKI is osmotic nephrosis, where pinocytosis and accumulation of HES molecules in renal tubular cells result in subsequent cell swelling and dysfunction. This dysfunction may lead to increased secretion of induced injury biomarkers such as NGAL, KIM, clusterin, and osteopontin, and decreased reabsorption of filtered biomarkers such as NGAL and cystatin C. The lack of greater increases in urine AKI biomarker concentrations following HES administration to dogs in our study may indicate that dogs are less susceptible to osmotic nephrosis following HES administration than other species, or that canine tubular cell function is able to be maintained despite osmotic nephrosis OR a type 2 error * the frequency of sepsis was low in our study, at 17.5%. Sepsis has been postulated to increase the risk of HES-induced AKI"

Answer 264

"In the multivariable analysis, serum phosphorous concentration remained the only significant outcome predictor. Median sCr, urea, and phosphorous concentrations were significantly higher, and the venous blood pH was significantly lower in non- survivors compared with survivors "

Answer 265

The tubules, glomeruli, interstitium, and intra-renal blood vessels. *Tubular damage can arise from either ischemic injury (decreased renal perfusion) or nephrotoxic compounds (exogenous and endogenous). *Severe acute glomerulonephritis secondary to immune-complex disease causes glomerular damage. *Interstitial damage can result from acute interstitial nephritis secondary to medications or infectious etiologies (leptospirosis, pyelonephritis, etc.). * Lastly, vascular damage can occur secondary to injury to intra-renal vessels (thrombosis, hypertension, etc.)

Answer 266

TRUE - due to inadequate excretion of organic and inorganic acids such as phosphate and sulfate

Answer 267

0.9% NaCl and buffered crystalloids significant reduction in the risk of major kidney events within 30 days buffered solutions

Answer 268

Administration of synthetic colloids has been linked with the development of acute kidney injury (AKI) and the need for renal replacement therapy (RRT) in ICU patients, especially those with sepsis (27, 36). Findings from meta-analyses suggest this may depend on patient cohort, but did confirm a higher risk of AKI and conflicting reports on mortality In veterinary medicine, there is inconclusive evidence on the development of AKI in dogs and cats treated with hydroxyethyl starches (HES). The majority of the studies are retrospective, with inconsistent definitions of AKI (38–41). Extrapolating from human medicine, in most clinical situations, the risks outweigh the benefits and alternative volume replacement therapies should be used in place of HES.

Answer 269

Fluids should be gradually tapered when hydration and urine production are restored, fluid “in” and urine “out” are matched, and the serum creatinine has plateaued (i.e., no further improvement at this stage). The authors recommend decreasing the fluid rate by 15–20% every 8 h, with the goal of discontinuing intravenous fluids in a 48 h period.

Answer 270

A furosemide stress test (1–1.5 mg/kg IV bolus) can be administered to oliguric patients that are assessed to be euvolemic or fluid overloaded to accurately determine AKI progression and need for renal replacement therapy. *has not been studied in veterinary medicine, but extrapolating from humans, a response of 1.5ml/kg/h roughly equates to the 200 mL over the 2 h time interval. Repeated administration of furosemide in a non-responsive patient can lead to adverse effects such as ototoxicity, which has been reported in humans.

Answer 271

"If renal replacement therapy is not available, diuretics may help control hyperkalemia by increasing distal tubular flow and allow more liberal administration of nutrition and medications with less risk of volume overload. The use of diuretics to increase urine output does not improve renal function. "

Answer 272

Selective postsynaptic dopamine receptor (DA-1) agonist that causes more potent renal vasodilation and natriuresis than dopamine. it can also promote hypotension by decreasing systemic vascular resistance.

Answer 273

Mannitol * Good --> osmotic diuretic that decreases cellular swelling and may help to wash out obstructive casts and debris from the tubules. It may also serve as a free radi- cal scavenger *Bad --> contraidicated in DH, overhydration, and may worsen pulmonary edema (consensus guidelines in people suggest that mannitol not be used in patients with AKI, no studies in VM) Furosemide *Good --> decreased renal oxygen consumption and less ischemic damage. Might help mainly for management of fluid balance, hyperkalemia, and hypercalcemia, but any putative role in amelioration of the AKI course is unproven * Bad --> Anuric patients with minimal to no tubular flow are unlikely to have furosemide reach the site of activity, and therefore this drug is often ineffective in increasing UOP in these patients. Fenoldopam *A retrospective study of fenoldopam use for both dogs and cats with AKI demonstrated no improvement in survival or length of hospitalization in patients who were administered fenoldopam compared to those who were not Diltiazem * Good --> may improve renal blood flow through afferent arteriolar vasodilation, which may increase GFR and UOP. It may also be renoprotective by preventing the intracellular accumulation of calcium, which can trigger cellular necrosis. *Bad --> A retrospective study evaluating the effect of diltiazem in dogs with AKI secondary to leptospirosis did not identify significant improvements in rate of reduction of serum creatinine, recovery of renal function, or survival.

Answer 274

"Furosemide enters the tubular filtrate via active secretion within the proximal tubule as well as filtration of non-protein-bound furosemide across the glomerular filtration barrier Anuric patients with minimal to no tubular flow are unlikely to have furosem- ide reach the site of activity, and therefore this drug is often ineffective in increasing UOP in these patients."

Answer 275

Human studies have shown limited to no improvement in morbidity, mortality, or need for dialysis in established AKI. Additionally, even at low doses, dopa- mine is potentially toxic in critically ill patients and can induce tachyarrhythmias and myocardial ischemia [19]. Based on these data, dopamine is not currently recom- mended for treating AKI in humans or animals

Answer 276

o associated with pyelonephritis, prostatitis, concurrent systemic diseases and either systemic or local alterations in immunity o UTIs in intact male dogs are classified as complicated infections, since most have concurrent prostatic involvement. o Recurrent UTIs (defined as three or more UTIs during a 12-month period) are classified as complicated infections o any patient with an identifiable risk factor for UTI is considered to have a complicated infection

Answer 277

Periodic infection with Candida spp is reported in animals that receive chronic antibiotics or are immunocompromised

Answer 278

Staphylococcus spp, Proteus spp and Corynebacterium spp, The resultant cleavage of urea to ammonia is not only irritating to the bladder mucosa but increases urine pH and promotes crystalluria (dogs and cats) and struvite stone formation (dogs)

Answer 279

a urease-producing agent such as Proteus and Staphylococcus spp

Answer 280

FALSE - The inflammatory response is often dampened in disorders that impair host defenses, such as diabetes mellitus, hyperadrenocorticism, and feline leukemia virus. The presence of white blood cells in any number should not be used as a criterion for the presence or absence of infection."

Answer 281

TRUE - (Whether colony counts are relevant in animals is unclear

Answer 282

Amoxicilin TMS +/- Cephalexin (mentioned in Drobatz but not in ISCAID consensus)

Answer 283

Enterococci

Answer 284

o hypersensitivity reactions that include blood dyscrasias, hepatotoxicity, polyarthropathy and skin eruptions, as well as idiosyncratic events, such as keratoconjunctivi- tis sicca (KCS). o hypersalivation and anorexia are frequently observed following oral administration in cats Sulfonamide hypersensitivity reactions occur > 5 days after beginning therapy, and short courses of TMP/S may be effective and safe in some dogs with simple cystitis

Answer 285

Doberman Pinschers

Answer 286

aminopenicillins beta-lactamase stable antimicrobial (e.g. cephalexin, amoxicillin-clavulanic acid)

Answer 287

Methicillin-resistant staphylococci GI upset, reversible bone marrow suppression, and peripheral neuropathy affecting predominantly pelvic limbs

Answer 288

3–5 days 7– 14 days

Answer 289

Enterobacteriaceae

Answer 290

It is important that culture specimen submissions indicate that pyelonephritis is suspected to ensure that urine breakpoints are not applied *Interpretation of susceptibility data should be based on antimicrobial breakpoints for serum rather than urine drug concentrations.

Answer 291

• drugs known to have local or regional efficacy against Enterobacteriaceae. o A fluoroquinolone or cefpodoxime are reasonable first choices. o Cefotaxime and ceftazidime are options for IV administration.

Answer 292

In the absence of veterinary-specific data, the Working Group recommends 10– 14 days of treatment

Answer 293

FALSE - lipid soluble

Answer 294

o Clindamycin and macrolides (erythromycin, azithromycin) can effectively penetrate the blood-prostate barrier, but should only be used based on culture and susceptibility test results, and not for empiric therapy because of lack of efficacy against Gram-negative bacteria (they not active against the Enterobacteriaceae o Chloramphenicol reaches prostate fluid concentrations that are only 60% of the plasma concentrations in dogs and it is doubtful that it can reach therapeutic levels in dogs. o The blood-prostate barrier reduces the penetration of many drugs, such as penicillins, cephalosporins, aminoglycosides and tetracyclines. This barrier is typically considered to be less intact in acute prostatitis; however, these drugs should be avoided, regardless of in vitro susceptibility data, particularly in cases of chronic prostatitis. o Ciprofloxacin should not be used because of the unpredictable bioavailability in dogs and relatively poor prostate penetration compared to enrofloxacin"

Answer 295

Four weeks is typically recommended for acute prostatitis

Answer 296

Fosfomycin

Answer 297

If catheterization is still required and signs of bacterial cystitis are present, the recommended approach is to remove the catheter, collect urine by cystocent- esis, then place a new catheter. If this is not possible, the catheter should be removed, a new catheter placed and urine collected from the new catheter for culture. The first 3–5 mL of urine collected should be discarded before collecting the urine specimen for culture.

Answer 298

Staphylococcus pseudintermedius or, less commonly, by Proteus mirabilis.

Answer 299

Leptospira interrogans and Leptospira kirschneri *The most common serovars thought to infect dogs before the introduction of leptospirosis vaccines 30 years ago were Icterohaemorrhagiae and Canicola.

Answer 300

"renal or hepatic failure, uveitis pulmonary hemorrhage (LPHS) acute febrile illness abortion Hepatitis, hepatic fibrosis"

Answer 301

TRUE - may result from a decreased glomerular filtration rate sufficient to cause impaired renal concentrating ability. However, these patients also may be hyposthenuric.19,31 Experimentally, leptospiral infection causes decreased vasopressin responsiveness of the inner medullary collecting ducts,32 suggesting polyuria may result from acquired nephrogenic diabetes insipidus.

Answer 302

FALSE - Leptospires do not replicate outside of the host but may remain viable for weeks to months in soil saturated with urine.

Answer 303

Renal tubular infection by leptospires is associated with acute interstitial nephritis and tubular dysfunction, although acute tubular necrosis can occur in naturally infected dogs Histopathologic changes in the liver often aremild and can include mild to moderate scattered hepatic necrosis and mild neutrophilic periportal hepatitis.

Answer 304

The results of the MAT are not recommended to predict serogroups circulating in the dog population. Instead, studies involving isolation of lepto- spires from dogs are recommended for epidemiological purposes, aswellasfor selectionofantigensfor diagnostic assay development and vaccine design The MAT is a serogroup- rather than a serovarspecific test, because antibodies to serovars within the same serogroup cross-react extensively.

Answer 305

2–4 weeks 3–5 days 7–14 days 4-fold

Answer 306

* potential utility early in the course of untreated infection when antibody assays are frequently negative and antimicrobials have not yet been administered * They also can confirm active infection in animals with positive antibody test results that have a history of vaccination with leptospiral vaccines

Answer 307

Blood Urine

Answer 308

Low-cost rapid assays for IgM or leptospiral antigen that could be performed as point- of-care tests would be useful --> Use of rapid, broadly reactive antibody assays as screening tests before performing the more specific and cumbersome MAT may help decrease false negative test results relating to inadequate serovar inclusion in the MAT and negate the need for subsequent MAT testing in dogs that test nega- tive by screening assays.

Answer 309

* the consensus panel recommends treatment of canine leptospirosis with doxycycline, 5mg/ kg PO or IV q12h for 2 weeks * If vomiting or other adverse reactions preclude doxycycline administration, dogs with leptospirosis should be treated with ampicillin, 20mg/kg IV q6h, with dose reduction for azotemic dogs. --> Ampicillin should not be administered orally be- cause it is not reliably absorbed from the gastrointestinal tract. * Penicillin G (25,000–40,000U/kg IV q12h) also could be used. * Azithromycin also may be effective. (CONSENSUS DOES NOT COMMENT TOO MUCH ON IT THOUGH..)

Answer 310

* First generation cephalosporins appear less effective * leptospires are resistant to chloramphenicol. * Fluoroquinolones use is controversial --> Concurrent fluoroquinolone use is not recommended in dogs with leptospirosis because it contributes to antimicrobial resistance in other bacteria.

Answer 311

2–4 weeks only 1–3 treatments

Answer 312

* Provided severe respiratory complications are absent, the prognosis for dogs treated early and aggressively in the course of leptospirosis with appropriate antimicrobi- al drugs and IV fluids, with or without diuretics, is good, especially when intermittent hemodialysis is available. * Survival rates of approximately 80% have been reported, both among dogs treated conservatively and those treated with dialysis * The prognosis for dogs developing se- vere respiratory complications is poorer.

Answer 313

* Successful treatment is associated with gradual return of serum urea and creatinine concentrations to reference ranges within 10–14 days (although regeneration of damaged renal tissue may continue for over 4 weeks after treatment) * The bilirubin concentration may decline more slowly than the activities of serum ALT and ALP. * Platelet counts often improve within 1 week of initiating antimicrobial treatment.

Answer 314

FALSE - Because many of these dogs are critically ill and require frequent monitoring, and leptospires are not readily transmitted between dogs, housing in isolation is not necessary

Answer 315

Before initiating antimicrobial therapy, and within the first 2–3 days of treatment

Answer 316

With disinfectant solutions (eg, 1 : 1 aqueous dilution of 10% bleach solution) * Iodine-based disinfectants, accelerated hy- drogen peroxide, and quaternary ammonium solutions also are effective

Answer 317

Bivalent vaccines --> containing Icterohaemorrhagiae and Canicola are 4-serovar vaccines --> containing serovars Icterohaemor- rhagiae, Canicola, Grippotyphosa, and Pomona

Answer 318

"Naturally occurring canine leptospirosis has been reported after vaccination with bivalent serovar Icterohaemorrhagiae and Canicola vaccines. The panel is unaware of leptospirosis in dogs that have been fully vaccinated with 4-serovar vaccines"

Answer 319

They also protect for at least 12 months.

Answer 320

Anaphylactoid reactions --> There is anecdotal evi- dence from veterinarians and industry that the prevalence of these reactions is decreasing, and may be similar to the rate induced by vaccines for other pathogens

Answer 321

Annual vaccination with 4-serovar vaccines is recommended for at-risk dogs, regardless of breed

Answer 322

Evidence of recurrent leptospirosis in dogs after proper treatment is lacking. Nevertheless, annual vaccination for dogs that have recovered from leptospirosis could be considered, because such dogs are at risk of on- going exposure, and whether or not life-long immunity results from natural infection is unknown. The duration of immunity in dogs after natural infection is likely to be at least as long as that induced by vaccination, and thus initial vaccination after recovery should occur 1 year after recovery.

Answer 323

8-12 weeks

Answer 324

urinary acidifier

Answer 325

36.2 ± 26.6 days

Answer 326

Urate Xanthine

Answer 327

Urate and cystine

Answer 328

Cystinuria 2-mercaptopropionylglycine (2-MPG, Tiopronin, Thiola)

Answer 329

Catheter retrieval voiding urohydropropulsion (not successful if patient presents with urethral obstruction) * Sizes of uroliths that may be retrieved with this technique are o ~ 1 mm in male cats, up to 5 mm in female cats o ~ 1–3 mm in male dogs, and up to 10 mm in female dogs Transurethral cystoscopic stone removal (with or without use of laser lithotripsy) - (not recommended in male cats) Mini-laparotomy-assisted cystoscopic stone removal/percutaneous cystolithotomy (PCCL) - (minimally invasive procedure of choice for male dogs and cats because the diameter of the male urethra limits insertion of a cystoscope with operating channel)

Answer 330

Nephrostomy tube Ureteral stent SUB

Answer 331

calcium oxalate

Answer 332

Fluid diuresis, a ureteral muscle relaxer (alpha-adrenergic blockade), and mannitol (0.25 g/kg bolus IV then 1 mg/kg/min CRI for 24 hours) As long as the patient is not overhydrated, hyperkalemic, oliguric, or showing evidence of progressive renal pelvic dilation on daily imaging success 8–13% of cases, stones move into different positions to allow urine to pass, but the stone itself not actually moving out of the ureter - high risk of re-obstruction If medical management fails to encourage stone passage after 24–48 hours  consider: nephrostomy tube placement, ureteral stenting, and the placement of a subcutaneous ureteral bypass (SUB) devices

Answer 333

Percutaneous nephrostomy tube placement - A locking loop pigtail catheter is recommended (5 or 6 Fr) to decrease the risk of inadvertent tube removal or urine leakage

Answer 334

Cause: physical obstruction (calculus, urethral plug, stricture, neoplasia) vs functional obstruction (idiopathic 50% of cases) Idiopathic (FIC)--> Appears to be a sterile inflammatory process--> maybe a sympathetic and hypothalamic-pituitary-adrenal imbalance brought about by stressful situations. Results in impaired blood flow and release of inflammatory mediators which cause edema, smooth muscle spasm, and pain within the LUT. In general --> Pressure necrosis and mucosal injury will occur -> subsequent reduction of GFR. Within 24–48 hours of obstruction, the kidney’s excretory ability ceases, resulting in an accumulation of BUN, creatinine, phosphorus, potassium, and H in the blood. Uremia -> depression, nausea, vomiting, and anorexia. Decreased intake + potential GI losses -> dehydration -> hypovolemia Metabolic acidosis -> denaturing of proteins, enzymatic dysfunction, and catecholamine hyposensitivity.

Answer 335

TRUE - BUT, another similar study failed to find this association

Answer 336

>2ml/kg/h Accumulation of osmotically active substances in the blood (osmotic diuresis) tubular epithelial dysfunction medullary washout antidiuretic hormone resistance increases in natriuretic factors brought about during the obstructive process Proposed incidence --> 37% when corrected for rate of fluid administration

Answer 337

Reported recurrence rates of 15–40%. Potential factors affecting recurrence include size or duration of indwelling urinary catheter, use of antispasmodic agents, patient age, and indoor-outdoor lifestyle; however, different studies offer conflicting results.

Answer 338

TRUE - however, some studies found more rapid improvement of acid-base values with balanced solution

Answer 339

polypropylene (A) - (traditional “tomcat” catheter) polyvinyl (B) - (red rubber catheter) polytetrafluoroethylene (C) polyurethane (D) A>>>>D reactivity

Answer 340

Polyvinyl catheters are softer and typically only come close-end with side-holes

Answer 341

phenoxybenzamine, acepromazine, and prazosin

Answer 342

Appears to be less effective than other medications the pharmacological effects of phenoxybenzamine may be delayed for up to a week, thereby making it potentially less useful in the immediate postobstructive period.

Answer 343

The diameter is designated using the French (Fr) scale. The scale value, when divided by 3, is the outside diameter of the catheter in milli- meters; that is, a 12 Fr catheter has an outside diameter of 4 mm.

Answer 344

AA pressure Decreased NaCl delivery to the macula densa

Answer 345

Spironolactone

Answer 346

"90 - 95% Organic Acid Transporters (OAT) Proximal tubule"

Answer 347

Decreased IC water Rheologic properties free radical scavenger

Answer 348

Improves GFR Rheologic properties --> improved blood flow decreases absorption of urea and sodium better tubular flow

Answer 349

Loop diuretics Thiazides

Answer 350

Spironolactone

Answer 351

1) Distal tubular acidosis (Classic or type 1) * Defective acid excretion in the presence of normal GFR * alpha intercalated cells are unable to excrete H ions to the tubular lumen * K is excreted instead, dragged by the negative lumen (can cause hypokalemia) * Since urine pH>6ish -> prompt to nephrolithiasis and nephrocalcinosis 2) Proximal tubular acidosis (type 2) * PT fails to reabsorb HCO3- * However, distal nephron functions normally and urine can still be acidified * characterized by hyperchloremic metabolic acidosis * can be accompanied by other abnormalities of the proximal tubular function (Fanconi syndrome) 3) Combined (Type 3) *Combined type 1 and 2 - rare 4) Hyperkalemic (type 4) * caused by decreased aldosterone release or activity (hypoaldosteronism) * decreases excretion of H and K --> then hyperkalemia and acidosis

Answer 352

Increased urine pH (>6) in the presence of acidosis (HCO3- is moderately to markedly decreased) --> H ions are not effectively secreted in the collecting ducts to acidify the urine.

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