Renal urinary Flashcards

Question

Describe the glomerular capillary endothelial membrane (of the filtrate barrier) structure and function?

Answer 1

Layer 1; Dense endothelial layer with fenestrations (pores of ~70nm) which allow free passage of water, solutes and proteins. Cells cannot pass and are trapped in the vasculature.

Answer 2

Comprised of 3 layers (inner->outer) 1) lamina rara interna 2) lamina densa 3) lamina rara externa The lamina rara externa if fused to podocytes. The basement membrane has a net negative chare that repels proteins (also carry a negative charge) and reflects them back into the vasculature.

Answer 3

Layer 3 of the filtration barrier. Glomerular capillaries are ensheathed in tentacle like processes from the podocytes. The podocyte tentacles, and "toes" that come off them form gaps in which a gelatinous filtration slit diaphragm lives. This filtration slit diaphram prevents proteins entering the bowmans space

Answer 4

πgc is ~25mmHg when it enters the glomerulus. This is the same as in the rest of the circulation. As water and solutes pass through into the bowmans space, protein is left behind. Blood looses 15-20% of its total volume to filtrate during passage through the capillary netweork increasing the colloid oncotic pressure to the point that this ~35mmHg when it enters the efferent arteriole

Answer 5

πbs In healthy individuals it should be 0 as proteins are prevented from entering the BS by the basement membrane and filtration diaphragm

Answer 6

Pbs, is ~15mmHg due to the large veolume of fluid that enters this space from the higher driving hydrostatic pressure in the capillaries of the glomerulus (~60mmHg)

Answer 7

No, it is higher. Glomerullar Pgc is ~60mmHg, which is ~25mmHg higher than other capillary beds.

Answer 8

Through changes in glomerular capillary surface area, which affects K f. The role of mesangial cells is minor com- pared with that of glomerular arterioles, however

Answer 9

Pgc, which is determined by the aortic pressure, renal arterial pressure and by changes in afferent and efferent vascular resistance

Answer 10

It reduces GFR and Puf. This is because contriction decreases glomerular blood flow. Dilation is the opposite

Answer 11

Constriction increaseds vascular resistance and increases pressure of the glomerular blood increasing GFR and Puf. Dilation reduces pressure and allows blood to flow out of the network faster reducing GFR and Puf.

Answer 12

1) Local vascular autoregulation; maintain RBF and optimise GFR 2) Central homeostatic control; Occurs through the atonomic nervous system can overide the local control and it will do so to adjust vlood volume and blood pressure.

Answer 13

1) Autoregulation; 2) Myogenic response 3) Tubuloglomerular 4) Paracrine 5) Central

Answer 14

Glomerular disease damages the filtration barrier and increases Kf, thereby allowing cells and proteins to pass into the tubule.

Answer 15

Glomerular disease can be divided into two broad and overlapping syndromes based on the characteristics of proteins and cellular debris contained within urine (urine sediments) and the associated symptoms: nephritic syndrome and nephrotic syndrome Nephrotic syndrome is characterized by severe proteinuria (loss of protein in the urine), hypoalbuminemia (low levels of albumin in the blood), and edema (swelling), while nephritic syndrome is marked by hematuria (blood in the urine), hypertension, and moderate proteinuria. | Nephritic rhyme with haemolytic -> aka blood

Answer 16

associated with diseases that cause inflammation of the glomerular capillaries, mesangial cells, or podocytes (glomerulonephritis). Inflammation creates localized breaches in the filtration barrier and allows cells and modest amounts of protein to escape into the tubule and appear in urine (proteinuria). Red cells typically collect and aggregate in the distal convoluted tubule and then appear in urine as tubular red cell casts

Answer 17

Nephrotic syndrome refers to a set of clinical findings that include heavy proteinuria (>3.5 g/day), ipiduria, edema, and hyperlipidemia. Cell casts, which are characteristic of an inflammatory process, are absent

Answer 18

Nephrotic syndrome reflects a general deterioration of the renal tubule (nephrosis) that includes degradation of glomerular barrier function and is a frequent cause of mortality in patients with diabetes mellitus. Loss of plasma proteins in urine causes plasma oncotic pressure to fall and accounts for the generalized edema associated with nephrotic syndrome. Hyperlipidemia reflects increased lipid synthesis that helps compensate for loss of lipids in urine.

Answer 19

The loop of Henle comes into direct contact with the afferent and efferent arterioles after returning from the medulla. The TAL wall is modified at the contact site to form a specialized sensory region called the macula densa. The macula densa monitors Na and Cl concentrations within the tubule lumen, which, in turn, reflect RBF and GFR. Na and Cl permeate macula densa cells via a Na-K-2Cl cotransporter located in the apical membrane. Cl immediately exitsvia a basolateral Cl channel, causing a membrane depolarization whose magnitude is a direct reflection of tubule fluid NaCl concentration.

Answer 20

Mesangial cells provide a physical pathway for communication between the sensory (macula densa) and effector (arteriole) arms of the TGF system. All cells in the JGA are interconnected via gap junctions , which allows for direct chemical communication between the system components.

Answer 21

The afferent arteriole is notable for its adenosine receptor and for renin-producing granular cells within its walls. A) Adenosine receptor; A1 receptors are bound to a downregulatory G protein–coupled receptor -> reduces cAMP pathway. cAMP normally inhibits smooth muslce contractily via PKA. Thus when the afferent arteriole binds adenosine it constricts B) Granular cells; secrotory cells which contain renin granules. Release rening -> RAAS increase -> increase ANGII whuc is vasoactive

Answer 22

These have A2 (adenosine 2 receptors) which bind adenosine -> Gprot -> increase cAMP -> efferent arteriolar dilation

Answer 23

- Stabilises RBF and GFR during mean arterial pressure (MAP) changes. - GFR remains stable with MAPS between ~80-180mmHg)

Answer 24

Myogenic response - MEchanoreceptors in the smooth muscle of afferent arterioles cause a calcium release during vascular stretching causing vascular constriction - this myogenic response stabilises GFR and RBF during chnages in posture

Answer 25

- autoregulatory mechanism mediated by the juxtaglomerular apparatus (JGA) - Complex involves the renal tubule, mesangial cells and afferent/efferent arteioled. - Adjusts RBF and GFR flow through th etubules

Answer 26

several hormoes are involved - Prostaglanding and NOX; dilate glomerular arterioles and increase RBF and GFR. May be released in response to ANGII vasocostriction in shock - Endothelins; local vasocostrictions released in responde to ANGII or when glomerular flow rates are damagingly high -ANGII; RAAS is the primary autoregulation system which regulates RPF and GFR. ANGII is the hormonal link between GFR and blood pressure

Answer 27

kidney governs total body water and Na content, which, in turn, determines blood volume and MAP. The kidney also receives 10% of cardiac output at rest, a significant blood volume that might be used to sustain more critical circulations (e.g., cerebral and coronary circulations) in the event of circulatory shock Renal blood flow is, thus, subject to control by the ANS, acting through neural and neuroal and/or endocrine pathways.

Answer 28

1) Neural 2) endocrine

Answer 29

Glomerular arterioles are innervated by noradrenergic sympathetic terminals that activate when MAP falls. Sympathetic activation raises systemic vascular resistance by restrict ing blood flow to all vascular beds, including the kidneys. Mild sympathetic stimulation preferentially constricts the efferent arteriole, which reduces RBF while simultaneously maintaining GFR at sufficiently high levels to ensure continued kidney function. Intense sympathetic stimulation severely curtails blood flow through both glomerular arterioles, and urine formation ceases. In cases of severe hemorrhage, prolonged occlusion of arteriolar supply vessels can cause renal ischemia, infarction, and failure

Answer 30

Hormonal regulation of RBF is mediated principally by epinephrine and atrial natriuretic peptide (ANP). Epinephrine is released into the circulation following sympathetic activation and stimulates the same pathways as does norepinephrine released from sympathetic nerve terminals. ANP is released from cardiac atria when they are stressed by high blood volumes. The ANP receptor has intrinsic guanylyl cyclase activity that dilates the afferent arteriole and increases RBF. It also relaxes mesan gial cells to increase filtration barrier surface area. The net result is an increase in RBF and GFR and salt and water excretion

Answer 31

ICF 66% (2/3) ECF 33% (1/3)

Answer 32

Plasma 1/4th (25%) Interstitial fluid 3/4th (75%

Answer 33

Cations; K, Mg Anions; protein and organic phosphates (ATP, ADP, AMP)

Answer 34

Cations; Na Anions; HCO3 and Cl

Answer 35

The interstitial fluid has the same composition just with a lot less protein. Thus ICF is an ultrafiltrate of plasma

Answer 36

Total body water; 60% ICF; 40% of body weight ECF: 20% of body weight

Answer 37

Osmolarity = concentration of solute particles Normal between 275-297mOsm/Kg Pos= 2xNa + (glucose/18) + (BUN/2.8)

Answer 38

1) osmolarity does not change even if ECF goes up as the solution is isotonic (i.e solutes do not shift between ECF and ICF) 2) PCV drops, due to the addition of diluting volume. TS drops too, because protein is diluted 3) BP increases due to the addition of intravascular volume

Answer 39

1) ECF decreases due to volume loss, but osmolarity stays the same due to osmosis between the ECF and ICF 2) haemocrit haemoconcentrates, and TS becomes more concentrate (ie PCV increases, and TS increases) 3) BP drops due to loss of ECF

Answer 40

1) ECF colume increases because osmoles (NaCl) have been added to the ECF drawig fluid from ICF - ICF volume decreases as a result 2) PCV and TS decrease due to volume expansion of ECF 3) BP increases due to volume expansion of the ECF

Answer 41

hyposmotic volume expansion 1) ECF osmolarity decreases because water is retained 2) PCV does not change because water shifts into the RBC, making them swell, offsetting the dilution 3) Plasma protein concentration decreases due to increased ECF 4) ICF osmolarity decreases as osmosis is trying to equilibrate this with the ECF

Answer 42

Hyposmotic volume contraction 1) osmolarity of ECF decreases; lack of aldosterone results in lack of NaCl reabsorbtion and kidneys excrete more NaCl than water 2) ECF volume decreases, while ICF increases, as water is not lost as much as NaCl, so by osmosis it entercs the cells to equilibrate ICF and ECF. 3) water entering the cells causes volume expansion 4) haematocrit increases because of decrease ECF volume and because RBC swell as a result of water entry 5) arterial BP decreases due to decrease ECF

Answer 43

C=UV/P C= clearance ml/min or ml/24h U= urine concentration (mg/ml) V= urine volume/time (ml/min) P= plasma concentration (mg/ml)

Answer 44

renal blood flow is proportional to the pressure difference between the renal artery and renal vein. It is inversely proportional to the vascular resistance in the renal vasculature

Answer 45

Decreases renal blood flow. Occurs due to sympathetic activation and angiotensin II. Costriction increases glomerular pressure increasing GFR - this is called the protective effec

Answer 46

These dilate the afferent arteriole increasing renal blood flow but decreasing glomerular pressure. Decreasing glomerular pressure decreases GFR (hyperfiltration is increased with increased glomerular pressure)

Answer 47

They increase renal blood flow decreasing GFR. these are Prostaglandin E2 and I2, Bradykinin, NO, dopamine,

Answer 48

Dilates afferent renal arteriole, and to a lesser extent constricts efferent arteriole, increasing renal blood flow, and GFR

Answer 49

Accomplished by changing renal vascular resistance. Two mechanisms; 1) myogenic - renal afferent arteriole contracts in response to stretch. This increased rena arterial pressure stretches the arterioles, which contract to increase resistance to maintain constant flow 2) tubuloglomerular feedback; increased renal arterial pressure increases the delivery of fluid to the macula densa. Macula densa senses an increased load and causes constriction of nearby afferent arteriole, increasing resistance Less Cl-> macula sense signals to juxtaglomerual cells -> produce renin -> produce angiotensin II -> vasocostriction of efferent arteriole -> decrease RBF but increase GFR

Answer 50

Increases GFR. High protein diet results in Na and Cl reabsorption (trying to bring in more water to maintain concentration). Increased Na and Cl delivery to the macula densa results in increasing GFR via the tubuloglomerular feedback

Answer 51

Clearance of inulin test; GFR =[Uinulin]V/[Pinulin] V= urine flow rate (ml/min)

Answer 52

Both serum BUN and CREA increase with decreased GFR. BUN increases more than serum creatinine resulting in an increase in BUN:Crea ration (>20:1)

Answer 53

Hypovolemia increases UREA reabsorption in the proximal tubule. Vasopressin is activated with hypovolemia, increasing H2O reabsorption in the collecting ducts. This concentrates BUN, resulting in increased passive reabsorption.

Answer 54

The fraction of renal plasma flow accross the glomerular capillaries; Filtration fraction =GFR/RPF

Answer 55

0.20 This means 20% of renal plasma flow is filtered. The remaining 80% leaves the glomerular capillaries by the efferent arterioles.

Answer 56

the net ultrafiltration pressure accross the glomerular capillaries

Answer 57

Glucose=GFRx[P]glucose It is determined by the plasma concentration of glucose

Answer 58

The Na-glucose cotransporter in the proximal tubule. The limiting factor is the limited number of these transporters

Answer 59

80-120mg/dl However, stressed cats can go up to 300

Answer 60

It is the point at which the glucose transporters are saturated.

Answer 61

At 250mg/dl all glucose can be re-absorbed (in the normal kidney) as there are enough Na-Glucose transporters in the proximal tubule. Tm (full saturation) is ~350mg/dl

Answer 62

The threshold is 250mg/dl. at <250mg/dl, the proximal tubule has enough Na-Glucose transporters to re-absorb all the glucose.

Answer 63

Tm, is the maximum saturation point of the Na-Glucose transporters and is reached at Bg 350mg/dl. All glucose after this point is excreted in the urine

Answer 64

Tm = transport maxiumum. aka the maximum amount of glucose that can be reabsorbed

Answer 65

PAH filtration increases in direct proportion to PAH plasma concentration.

Answer 66

Protein (not usually excreted), Na, Glucose, Amino acids, HCO3 and Cl

Answer 67

Those that are freely filtered, but not reabsorbed or secreted - e.g. Inulin

Answer 68

PAH>K (high -K diet)> unulin>urea> Na>glucose >amino acids and HCO3

Answer 69

a polysacharide commonly found as a plant fiber

Answer 70

Nonionic diffusion occurs for weak bases and weak acids

Answer 71

HA is an uncharged and lipid soluble weak acid, which can back diffuse from urine to blood A- is a charged lipid insoluble weak acid which cannot back diffuse from urine to blood

Answer 72

BH+ and B. B form is uncharged and lipid soluble and can back diffuse from urine to blood BH is a charged and lipid-insoluble substance which cannot back diffuse from urine to blood

Answer 73

In acidic urine; The HA form predominates - there is more back diffusion and secretion of weak acid A The BH form predominates - there is less back diffusion, and there is increased excretion of weak base (e..g morphine can be increased in acidifying urine )

Answer 74

A- predominates; there is less back diffusion and there is increased excretion of weak acid - e.g. salicilyc acid can be increased in alakalanizing urine B form predominates as there is more back diffusion and there is decreased excretion of a weak base

Answer 75

along the whole nephron

Answer 76

This compares the concentration of a substance in the tubular flud at any point along the nephron with the concentration of plasma

Answer 77

TF/P=1 ; [Na] in the plasma and tubular fluid is identical TF/P<1; [Na] reabsorbtion has been greater than the absorbtion of water TF/<1; [Na] absorption has been less than H2O, OR the excretion of Na has occurred.

Answer 78

[Na] in the tubular fluid is 80% of [Na] in the plasma

Answer 79

Inulin is used as a marker of water reabsorption along the nephron. Inulin is increased as water is reabsorbed. As inulin moves freely (not absorbed or secreted), the concentration of this in the tubule solely depends on how much water is diluted it

Answer 80

1.0 Na is freely filtered accross the glomerular capillaries, so the [Na] in the bowmans is the same as the plasma. Na is also reabsorbed along the whole nephrons and very little is excreted

Answer 81

=1 - (1)/([TF/P]inulin

Answer 82

This is the proximal convoluted tubule, as it is the site which absorbs the most Na compared to the rest (67%)

Answer 83

Isosmotic, as Na and H2O reabsortion in the proximal tubule are exactly proportional. Therefore, TF/Pna=1 and TF/Posm=1

Answer 84

1) Reabsorbs Na, H2O, HCO3, glucose, AA, phosphate and lactate 2) Na is reabsorbed by cotransport with Glucose, AA, phosphate and lactate 3) Na is reabsorbed by countertransport via Na-H exchanger, whih is linked directly to the reabsorption of filterd HCO3 4) Carbonic anyhydrase inhibitors (e.g. acetazolamide) are diuretics that act o the proximal tubule by inhibiting reabsorbtion of filtered HCO3

Answer 85

Carbonic anyhydrase inhibitors (e.g. acetazolamide) are diuretics that act on the proximal tubule by inhibiting reabsorption of filtered HCO3

Answer 86

Na is reabsorbed with Cl-

Answer 87

Maintains a constant fractional reabsorbtion (2/3rd -67%) of the filtered Na and H2O e.g. if GFR inceases, filtered Na load also increases. However, the glomerulotubular balance functions such tha Na reabsorbtion will also be increased, otherwise, more Na would be lost

Answer 88

Starling forces in the peritubular capillareis, which alter reabsorbtion of Na and H2O in in proximal tubule

Answer 89

Increases fluid reabsorption; volume contraction increases peritubular capillary protein concentration (πc) and decreases Pc of the peritubular capillary blood. These two result in increased proximal tubular reabsorption

Answer 90

πc - protein oncotic pressure High πc -fluid reabsorbtion Low πc - fluid excretion This is done to maintain homeostasis as high πc is consistent with protein concentration and hypovolemia

Answer 91

Capillary hydrostatic pressure

Answer 92

It will decrease πc and increase Pc resulting DECREASED peritubular reabsorption

Answer 93

Na reabsorption is always proportional to H2O (i.e. TF/P =1), so it is a level line. Inulin is not absorbed, so its concentration grows steadily. Most glucose and amino acids are absorbed in the early portion of the proximal tubule so it drop off fast. In the proximal tubule, Cl is proportionally abdorbed less than H2O and mostly occurs in the late tubule so its concentration initially increases

Answer 94

- reabsorbs 25% of filtered Na - contains the Na-K-2Cl cotransporter in the luminal membrane - site of loop diuretic action -> inhibit Na-K-2Cl - impermeable to water, thus NaCl is reabsorbed without water - lumen has a positive potential difference. although Na-K-2Cl appears electronicaly neutral, some K diffuses back into the lumen making it electronically positive

Answer 95

impermeable to water thus, NaCl is reabsorbed without water. As a result, tubular osmolarity decreases to less than their concentrations in the plasma (TF/PNa and TF/Posm <1.0)

Answer 96

Reabsorb 8% of filtered Na together Early; - Reabsorbs NaCl by Na-Cl cotransporter - site of action of thiazides - impermeable to water (also diluting segment like thick ascending) - called the corticula diluting segment Late +collecting duct - Principal cells; - reabsorb Na and H2O and secrete K - alpha intercalated; - secrete H+ by H-ATPase (stimulated by aldosterone) - Reabsorb K by an H,K ATPase

Answer 97

Aldosterone; increases Na reabsorbtion and K secretion Antidiuretic hormone; Increases H2O permeability by depositing aquaporins 2 (AQP2) H2O channels in the luminal membrane K-sparing diuretics (spironolactone) --> decrease K secretion

Answer 98

When Antidiuretic hormone is upregulated (or vasopressin is given), we have deposition of aquaporin in two channels in the luminal side of the distal tubule and collecting duct. Without this, this region is not able to reabsorb water

Answer 99

- spironolactone - Tramterene - Amiloride

Answer 100

- torsemide - furosemide - bumetanide - ethacrynic acid

Answer 101

NaCl transporter in the early distal tubule

Answer 102

Shift out causes hyperkalaemia Shift into causes hypokalaemia (or loss)

Answer 103

When urinary excretion of K exactly equals intake of K in the diet

Answer 104

- Diet intake (appropriate or excessive) - Aldosterone levels - insulin levels (hyperglycaemia sequesters this into the cell from the ECF) - Acid: base status

Answer 105

Filtration occurs freely accross the bowman space TF/Pk=1

Answer 106

- proximal tubule 67% (along with Na and H2O) - Thick ascending 20% (involves the Na:K:Cl cotransporter) - Distal tubule and collecting duct (ether absorb the rest or excrete depending on dietary intake) - H; KATPase in alpha-intercalated cells

Answer 107

- passive filtration accross the bowmans capsule, but if TF/P>1 with this then, H:K ATPase in the late part of the distal convoluted tubule activate, and the principal cells of the early distal convoluted tubule also activate

Answer 108

Takes several hours. This is a hormone which needs to synthesise new Na channels (ENaC)

Answer 109

- basolateral membrane Na-K pump actively pump K into the principal cell of the distal tubule (this allows for high intracellular K concentrations ) - luminal membrane K passively secreted into the lumen through K channels. The magnitude of this is driven by the chemical and electrical driving force of K accross the luminal membrane

Answer 110

1) Dietary intake 2) Aldosterone 3) Acid-base 4) loop diuretic /thiazide diuretics 5) K sparing diuretics 6) luminal anions

Answer 111

Diet high in K increases the driving force of K into the cells and thus secretion from the late distal tubule cells and vice versa

Answer 112

Increases K secretion Increased Na entry (through ENaC) through the luminal membrane and increased pumping of Na out of the cell through Na-K pump which increases K uptake into the principal cells. this increased K in the principal cells increases the driving force for secretion of K. Aldosterone also increases the number of luminal K channles

Answer 113

Hypokalaemia Increased aldosterone drives more Na into the principal cells whcih is then excreted into the blood through the Na:K exchanger. More K though is brought into the cell , increasing its driving force to be secreted. Aldosterone also increses the numebr of K transporters in the luminal membrane resulting in more K entering the lumen of the tubule

Answer 114

Hyperkalaemia Decreased Na reabsorbtion into the pricincipal cells means less Na:K cotransporter activity, thus more K is keps in the blood and not absorbed intracellularly

Answer 115

H and K exchange for each other across the basolateral cell membrane Acidosis decreases K secretion; Blood contains excess H; therefore, H pumped into the tubule across the basolateral membrane and K is contransported intp the cell. Thus hyperkalaemia Alkalosis increases K secretion; too little H+ in the blood, therefore H+ leaves the cell across the basolateral membrane, and K enters the cell, increasing the driving force

Answer 116

Diuretics increase flow rate trhough the late distal tubule diluting K concentrations. This increases driving force for K secretion Diuretics also increase Na secretion and delivery to the late distal tubule and collecting ducts, leading to increased Na entry across the luminal membrane of principal cells, which results in increased Na pumping out of the cells by the Na: K pump, increasing intracellular K this increasing the secretion driving force

Answer 117

spironolactone is an aldosterone receptor blocker. By blocking aldosterone, we have decreased Na entry into the cell and thus less function by the Na: K pump trying to pump the Na out. This means less K is pumped in from the blood, and thus, the driving force of K is lower, and we do not have a loss of K

Answer 118

Excess anions (e.g. HCO3) in the lumen cause an increase in K secretion by increasing the negatiity of the lumen and increasing the driving force for K excretion.

Answer 119

5% of total fluid volume, which is ~50ml/Kg

Answer 120

~20ml/kg (dog) ~10-15ml/Kg (cat)

Answer 121

the number of osmoles (ie solutes) per Kg of solvent (e.g. fluid). Normal ECF osmolarity is ~300mOsm/kg Na is the major extracellular cation, and it equates to; ECF osmolarity =2x([Na]) +[K]) +([glucose] /18) + ([BUN]/18)

Answer 122

Na is the major extracellular osmole, and K is the intracellular (hence, they are x2). BUN is an ineffective osmole, so it does not cause fluid shifts in and out of cells. Glucose if it gets high enough it will start causing fluid shifts and effecting the osmolality. K is not really relevant to the calculation as we now know that large shifts of K will not cause fluid shifts and therefore shifts in osmolarity

Answer 123

water loss/increase intake and increase intake or loss. If you have large increases in other solutes (like glucose) then Na will be diluted due to the fluid shift following the glucose

Answer 124

This occurs when a patient was hypovolemic for whatever reason (and would have had a high [Na]). However, they have then gone and replaced their fluid defecit with pure water which has reduced the Na and corrected the volume status.

Answer 125

Salt increase would result in hypervolemia If you have water loss you will be hypovolemic or normal

Answer 126

You have to look at volume status. This is because you can be hypervolemic with hypernatremia and and hyponatremic with hypovolemia (both should be the opposite). For example, the puppy with psychogenic polydipsia will be hyponatremic but with increased volume from the polydipsia, while the cat that has been vomiting a lot, and then drinking pure water will be hyponatremic with hypovolemia

Answer 127

99% Proximal tubule By osmosis following Na and other solutes

Answer 128

They are isosmotic. Both filtrate and blood have the same osmolarity as plasma, and nether changes with the re-absorption of water. This is because you are absorbing a bunch of solutes but also water, so the osmolarity does not change

Answer 129

20%, by osmosis

Answer 130

There is a progressive increase in osmolality from the cortex to the medulla along the proximal tubule, then the osmolarity starts to drp as the loop of henle is impermeable to water and re-absorbs solutes. by the time it reaches the proximal tubule the urine will be hyposmolar. Descending 300->1200-> 100 and volume drops

Answer 131

The ascending is permeable to water but not solutes, so we see concentration of the urine, so the osmolality of the filtrate goes up. However, the ascending limb is impermeable to water, so here we have re-absorbtion of solutes so osmolality will drop

Answer 132

This is also impermeable to water and it re-absorbed solutes so the osmolality drops to lower than the initial filtrate (<260mmOsm). This is becuase solutes are taken out and only water is left so osmolality drops

Answer 133

The final 15% of water is re-absorbed here and the final urine concentration is regulated here

Answer 134

this is upregulated or downregulated by vasopressing, aka antidiuretic hormone, which controls aquaporin molecules

Answer 135

BOTH osmoreceptors in the hypothalamus and baroreceptors (atrial wall, aortic arch and carotid body)

Answer 136

ADH is NOT excreted so what you see is the production of dilute urine as the collecting duct is impermeable to urine

Answer 137

The baroreceptors and osmoreceptors detect this, upregulate ADH from the neurohypophysis which increases aquaporin synthesis. This increases the channels in the luminal wall of the collecting duct resulting in H20 uptake concentrating urine

Answer 138

75-80% of phosphate 65-70% of Na and Cl- 65% of K 65% of Ca 25% of Mg (most in loop of henle)

Answer 139

the descending is pretty much impermeable to solutes so it does not really contribute The ascending; 15-25% of Na and Cl 25-30% of P 25% of Ca 65% of Mg (rule breaker)

Answer 140

Not much. Mostly K excretion with aldosterone

Answer 141

The Na-KATPase and this is energy-dependent. 3Na move for every 2K. This creates a gradient for Na absorbtion These are found; 1) proximal tubule 2) Thick ascending limb of the LOH 3) Distal convoluted tubule 4) collecting duct

Answer 142

There are different transporters for different segments which allow Na to move down the concentration gradient they created from Na:KATPase on lumuminal surface; - Proximal tubule part of proximal tubule Na:KATPase - Mid proximal tubule SGLT - Distal proximal tubule NHE3 - Thick ascending loop Na:K:2Cl - Distal convoluted NCC - Proximal collecting duct ENaC

Answer 143

Glucose, amino acid etc : Na cotransporter (concentration of each) Na: NH4 Na-H -> exchanger (AngII) Increases Na and H2O

Answer 144

Increases the osmolality of the tubular fluid, DECREASING the drive for Na and H2O reabsorption in the proximal tubule,

Answer 145

Uses the; - Na:K:2CL co-transporter - Na-H antiporter

Answer 146

Inhibits the Na-K-2Cl cotransported -> decrease reabsorbition of Na and H2O This also increases K excretion by blocking NaKCC exchanger, as the luminal Na:KATPase continues to work increase driving force of potassium intracellularly) Ascending limb of henle

Answer 147

Furosemide inhibits paracellular reabsorption of calcium (Ca) and magnesium (Mg) in the thick ascending limb of the loop of Henle (TAL) by diminishing the lumen-positive transepithelial voltage. This is because furosemide blocks the Na+/K+/2Cl- cotransporter (NKCC2), reducing sodium and chloride reabsorption, reducing the positive electrical potential within the lumen of the TAL. This positive potential is crucial for the paracellular movement of Ca and Mg, and its reduction by furosemide leads to decreased reabsorption and increased excretion of these ions.

Answer 148

Genetic mutation in the Na-K-2Cl co-transporter which causes hypercalcinuria and increased risk of Ca oxalate stones. It is one of the major causes of Ca oxalate stones in bulldogs, bassets and beagles

Answer 149

Na-Cl co-transporter

Answer 150

They act on the the Na-Cl cotransporter decreasing Na and H2O re-absorbtion in the distal convaluted tubule

Answer 151

Despite thiazides preventing re-absorbtion of Na and, therefore, H2O, this diuretic also increased water re-absorbtion in the proximal tubule therefore cancelling out the diuretic effect

Answer 152

Thiazides increase proximal tubule Na and H20 re-absorbtion. This increase in Na re-absorption means there is a positive electrical shift into the cell, which results in increased Ca reabsorption, too. This prevents the calcium being excreted in the urine where it can form Ca oxalate stones

Answer 153

By Na channels Aldosterone -> increased aldosterone, increased Na channels (ENaK) and therefore Na and H20 reabsorbtion

Answer 154

blocks aldosterone receptors, which downregulates the Na channels. The drug is a weak duretic (prevents H20 following the Na). However, it also prevents K excretion. There is a Na:KATPase on the vascular aspect. This normally pumps 3Na out and 2K in when the Na is active. This increase in intracellular K flows through K ion channels (ROMK) into the urine causing hypokalaemia. By blocking aldosterone, we reduce Na reabsorbtion (and H20) and therefore K loss

Answer 155

Most of it is paracellular re-absorption whcih is tightly linked to Na reabsorption so most of it occurs in the proximal tubule, followed by the thick ascending limb of the loop of henle. There is also some co-transport too, such as the Na:K:2Cl cotransporter in the loop of henle and the Na:Cl transporter in the distal convoluted tubule

Answer 156

This is based on the acid base status and the Cl is co-exchanged with HCO3 beta intercalated cells have Cl:HCO3 co-exchangers, so in acidosis more HCO3 is re-absorbed resulting in secretion of CL

Answer 157

mainly proximal convoluted tubule followed by thick ascending limb of the loop of henle and then the intercalated cells of the collecting duct

Answer 158

Proximal tubule; Paracellular re-absorbtion HEnle Na:K:Cl2 cotansport

Answer 159

the principal cells of the collecting duct. The Na:KATPase creates a Na gradient (lower in the cell) so that the ENaC Na channel can re-absorb Na from the collecting duct. This causes an increase in intracel K that then flows down a concentration gradient through the ROMK channels in the collecting duct Intercalated cells of the collecting duct; There is an energy dependent Na:KATPase which brings 2K into the cell and pumps out 3Na (this is how the urine is diluted as Na follows Na). As K builds in teh cell, the K exits via a H:K ATPase (H used to make bicarb which can then be secreted in the urine) and by diffusion down an electrockemical gradient

Answer 160

By paracellular re-absorbtion down an electrochemical gradient caused by Na in both the proximal (Na uses NHE3) and thick ascending limb of henle (NKCC2 Na pump). In the distal convoluted tubule, Ca is actively re-absorbed by the TRPV5 (via signlaing from TRMP1 bound to PTH. This then exits the cell via Na:Ca NCX1 receptor and the Ca pump PMCA4

Answer 161

This is the Na-K-2Cl transported in the thick ascending limb of henle which furosemide acts on

Answer 162

Parathyroid hormone is released increasing Calcitriol production and renal absorbtion of Ca. The PTH and calcitriol binds to PTHR1 Gprot recepors on the distal convoluted tubule (blood Side). This receptor upregulates NCX1(Na:K channel) and PMCA1b (Ca pump) pumping Ca out of the cell into the blood. The PTHR1 also, upregulates TRPV5 which re-absorbes Ca from the urine into the cell, which can then exit via NCX1 and PMCA1b

Answer 163

Int he distal convoluted tubule, Ca in the blood binds to CASR Gprotein which downregulates TRPV5

Answer 164

proximal tubule; cotransported with Na. There are several different types of Na:P cotransporters (eg. NaPi-IIa, NaPi-IIc, PiT-2). These are then trnasported out of the cell hydroxylated (HPO4 /H2PO4) by XPR1 receptors

Answer 165

PTH - it binds to PTHR receptors which then via PKA inhibit phosphorous co-transporters

Answer 166

they are made of microvilli to increase surface area as this is the site where most is re-absorbed

Answer 167

all Sodium-Glucose co transporter (SGLT1 & SGLT2) are used to move glucose against its concentration gradient. About 90% of the glucose is re-absorbed via SGLT2 receptors in the early part of the proximal convoluted tubule and the reminders is re-absorbed via SGLT1 receptor. On the basolateral side of the cell glucose diffuse through GLUT receptors via passive transport.

Answer 168

One of the amino acid transporters in the proximal tubule is counter tranpsorter that secretes cysteine into the urine

Answer 169

proximal tubule by the SLC family of transporters

Answer 170

Dalmations, black Russian terriers and English bulldogs. they have a mutation in the SCLA9 transporter which is normally involved in re-absorbing uric acid. This is both on the luminal aspect and plasma memembrane -> causing hyperuriaciduria

Answer 171

It is a major anti-oxidant in the plasma

Answer 172

Pelvic nerve – arise from the sacral plexus (S2-S3) - Possess both sensory and motor fibers (parasympathetic) Function: - Sensory fibers detect the degree of stretch of the detrusor muscle and bladder filling - Detrusor muscle contraction – via parasympathetic fibers (muscarinic cholinergic receptor) Pudendal nerve – - Possess somatic motor fibers Function: - Somatic motor control of the external urethral sphincter Involve in voluntary control of micturition Hypogastric nerve – arises from the L2 spinal cord segment Possess motor fibres (sympathetic) Function: - Detrusor muscle relaxation (β receptor) Internal urethral sphincter (α receptor)

Answer 173

It reduces due to the ureterorenal reflex The ureters are extensively innervated by pain receptors. If a ureter becomes obstructed It produces intense pain which triggers sympathetic system to cause constriction of the afferent and efferent arterioles thereby reducing urine output from this kidney.

Answer 174

Bladder fills -> dilates and sensory response relayed by pelvic nerve. Pelvic nerve -> parasympathetic motor input -> contraction of dextrusor. The bladder contracts and relaxes continuously. As it becomes more full, the contractions become stronger. If the bladder does not empty in 1-2 min, the reflex abates. As the bladder fills thour, the contractions become more frequent and stronger. Once the micturition reflex is powerful enough, the pudendal nerve becomes inhibited which causes relaxation of the external urethral sphincter. While the previous description of the micturition reflex is an autonomic reflex. It is usually inhibited or facilitated by the brain. These centers are located into the brain stem and cerebral cortex. These higher centers will exert final control of micturition as follow: 1) The higher center keeps the micturition reflex inhibited unless urination is desired 2) The higher center can prevent micturition by voluntary control of the external urethral sphincter 3) When urination is desired, the micturition reflex can be initiated and external urethral sphincter relaxed.

Answer 175

Atonic bladder and incontinence cause by destruction of sensory nerve fibers (Pelvic n). When this happens, the bladder will passively fill to capacity and overflow a few drops into the urethra. e.g. crush to sacral portion of spinal cord -> pelvic nerve damage. Overstretching of the bladder

Answer 176

caused by spinal cord damage above the sacral region. the micturition segments are still intact and can occurs but they no longer can be inhibited by the brain. Periodic, unannounced bladder emptying can occur. Causes; Damage to the spinal cord above the sacral segments

Answer 177

Urinary excretion rate= Filtration rate-reabsorption rate+Secretion rate

Answer 178

Endothelium of the capillary – the endothelial is perforated by thousands of small holes called fenestrae. The endothelial cells are strongly negatively charged which prevent proteins from filtering across the membrane. Glomerular basement membrane – surrounds the endothelium and made up of a meshwork of collagen, laminim, and proteoglycans. The latter are strongly negatively charged which prevent proteins from filtering across the membrane Podocytes – podocyte surrounds the capillaries, they are not continuous. These have finger-like projection called pedicels and spaces between the pedicels are referred to as slit pores.

Answer 179

thicker than normal capillaries membrane; however, it is much more porous. The membrane is selective in determine which molecules filter through based on their size and electrical charges.

Answer 180

It is smaller than the fenestrae of the capillaries so can pass, but, because it is negatively charged it gets repelled by the negative charge of the capillary endothelium and basement membrane

Answer 181

there is increased glomerular permeability to plasma proteins. On light microscopy, the glomeruli appear essentially intact; however, on electron microscopy, the podocytes and pedicles are seen to be detached from the basement membrane –> referred to as podocyte effacement. Suspected pathogenesis: T-cell secretion of cytokines and subsequent injury to podocyte. Eventually, this leads to proteinuria and hypoalbuminemia.

Answer 182

Glomerular capillary filtration coeficient (Kf) x Net filtration pressure 1) increase GFR 2) decrease GFR 3) decrease GFR 4) increase GFR 5) Increase GFR 6) decrease GFR

Answer 183

glomerular capillary membrane thickens which reduces Kf

Answer 184

obstruction of the ureter. The backpressure flow eventually increasing the hydrostatic pressure in Bowman’s capsule. Eventually this can lead to hydronephrosis

Answer 185

Two factors will influence the glomerular capillary colloid oncotic pressure: - Arterial plasma colloid osmotic pressure - The fraction of plasma filtered by the glomeruli (filtration fraction)

Answer 186

glomerular capillary hydrostatic pressure is the primary physiological means of regulating GFR.

Answer 187

(1) arterial pressure (2) afferent arteriolar resistance (3) efferent arteriolar resistance

Answer 188

- Constriction of afferent decreases glomerular filtration rate (less blood to kidney) The effect of constriction of the efferent depends on the severity of the constriction: - Modest constriction leads to an increase in hydrostatic pressure and an increase in glomerular filtration - Severe constriction (>3 x normal tone) tends to decrease GFR

Answer 189

It is high; however, the 25% of CO provided is more than is needed to meet the O2 requirements (this much is needed for filtration). The kidney consumes 2x more O2 than the brain but receives 7x more blood. High O2 utilization is due to the rate of active sodium re-absorbtion (Na:K ATPase is found in most cells and energy-dependent). IF GFR falls to 0m the the O2 consumption of the kidney falls to 1/4

Answer 190

They exist so that afferent/efferent vascular dilation/contraction can change the local renal blood pressure, in perspective of systemic BP, to modify GFR. Mechanisms are; - Sympathetic nervous system - Hormones - Internal renal control mechanism

Answer 191

Norepinephrine = reduction (contract vessels) Epinephrine =reduction (contract vessels) Endothelin = reduction (decrease capillary hydrostatic pressure) Angiotensin II = prevent reduction (several ways) Endothelial-derived nitric oxide= increase (increase blood flow to the kidney by dilating afferent) Prostaglandins= Increase (decrease SVR and increase flow to the glomerulus)

Answer 192

will preferably constrict efferent arterioles in most physiological conditions. ITs role is to maintain GFR In the presence of decreased blood flow as its secreted during hypovolemia / hyperosmolar conditions When it binds to its receptor it causes localize vasoconstriction. However, the afferent arterioles are protected from the effect due to the release of nitric oxide and prostaglandins. On the other hand, the efferent arterioles preferentially binds angiotensin II. In most physiological conditions, angiotensin II will increase glomerular filtration rate while decreasing blood flow to the kidneys.

Answer 193

NDAIDs inhibit prostaglandin synthesis. Prostaglandins normally cause renal afferent vasodilation and maintain GFR; thus, inhibiting them will result in decreased flow to the kidney as vasoconstriction occurs in their (and NO) absence.

Answer 194

1) Maintenance of delivery of oxygen and nutrients to tissue with normal level of waste removal 2) Maintenance of constant GFR and allow for precise control of excretion of water and solute In summary the role is to prevent extreme variations in renal excretion

Answer 195

macula densa measures CL - to determine renal arteriolar resistance and GFR. This system is designed to provide a constant delivery of NaCl in the distal tubule and prevent fluctuation in renal excretion that would otherwise occur. In parallel this system provides regulation of GFR. Two main components that work together: 1) afferent arteriolar feedback mechanism 2) efferent arteriolar feedback mechanism Both rely on the juxtaglomerular complex. This is made up of the macula densa cells and the juxtaglomerular cells in the walls of the afferent and efferent arterioles Decrease NaCl at the macula densa -> dilation of afferent arterioles and increased renin release (renin -> ang II which increases efferent vasocostriction) When there is ↓ GFR due to ↓ arterial pressure -> increased absorption of NaCl which is detected as ↓ NaCl by the cells of the macula densa. This has two effects: 1) Decrease vascular resistance of the afferent arterioles 2) Release of renin -> Ang II -> increase SVR of the affected arterioles -> restoring GFR

Answer 196

When arterial pressure increases, the glomerular afferent arterioles react by contracting their smooth muscle to increase resistance and prevent an increase in glomerular blood flow

Answer 197

lead to increased renal blood flow and glomerular filtration rate. Meals high in proteins –> high amino acid re-absorbtion with Na+ in the proximal convoluted tubules -> detected as decreased NaCl by the macula densa (AA contransports with Na) -> causes dilation of the afferent arterioles.

Answer 198

Na+ - K+ ATPase Hydrogen ATPase Hydrogen-Potassium ATPase Calcium ATPase Primary active transport through the tubular membrane is linked to hydrolysis of adenosine triphosphatase

Answer 199

- Na+/K+ ATPase pump - presence of a brush border - carrier proteins that bind Na+ on the luminal side and improve passive diffusion.

Answer 200

Luminal sider; SGLT1 and SGL2 co-transporters (use Na). 90% of the glucose is re-absorbed via SGLT2 receptors in the early part of the proximal convoluted tubule Basolateral passive diffusion down GLUT2 transporters. If the glucose needs to be re-absorbed into the cells, then it will use GLUT transporters which counter-exchange Na for the glucose (Na concentration gradient created by the Na:KATPase).

Answer 201

If there is a lot of substances that need to be reabsorbed (e.g. Glucose in a diabetic) not all of it will be able to be re-absorbed due to saturation of the receptors (this is the tubular load) Transport maximum is just the maximal transport rate at which a substance can be re-absorbed

Answer 202

(1) there is an electrochemical gradient for diffusion across the membrane (2) the permeability of the membrane for a substance (3) The time that the fluid containing the substance spend in the tubule This type of transport is referred to as gradient-time transport. Na+/K+ ATPase pumps will follow a gradient-time transport rather than a transport maximum.

Answer 203

It is coupled with Na movement. Water reabsorption by osmosis depends on tight junction and membrane permeability to water. Also; Aquaporin 1 -> proximal convoluted tubule (high permeability to water – due to great number of water channel). Found in the tight junctions and renal interstitium. Aquaporin 2 -> These are up and downregulated in the descending loop of henle and collecting ducts based on ADH concentration. This is what gives this region a variable permeability

Answer 204

There is no Aquaporin 1 in the tight junctions (and these become impermeable), and ADH does not regulate Aquaporin 2 in this area.

Answer 205

Re-absorb: Na+, Cl-, HCO3-, K+, glucose, and amino acids Secrete: H+, acids, base, toxins, etc.

Answer 206

furosemide, toresemined, ethacrinyb acid, Bumetadine

Answer 207

Found in the late distal tubule and cortical collecting duct. Majore role in acid:base secretion (control 30-40% of this) Type A; ecrete H+ by an hydrogen-ATPase pump and an hydrogen-K+ co-transporter. The H+ is generated by the action of carbonic anhydrase and water and carbon dioxide to form carbonic acid. For each H+ re-absorbed a bicarbonate ions (HCO3-) is created and made available for re-absorption. Key point: The Type A intercalated cells re-absorb HCO3- and secrete H+. cells secrete HCO3- and reabsorb H+ ions from the tubular lumen (opposite function of Type A cells) The bicarbonate Cl- cotransporter present on the tubular lumen of B cells has referred to as pendrin receptors.

Answer 208

Glomerular 1) re-absorb sodium (Na+) and secrete potassium (K+). The rate of absorption is highly dependent on hormones (esp. ADH) 2) Type A intercalated cells secrete [H+] via a hydrogen ATPase pump and H+-K cotransporter 3) Type B intercalated cells secretes large [HCO3-] 4) Water reabsorption (aka urine concentrating ability) - ADH dependent. Without ADH this area is virtually impermeable to H20 Medulla The final site to modify the urine 1) Water reabsorption - ADH dependent - only responsible for ~5% of H2O reabsorption though 2) permeable to urea 3) capable of secreting large volumes of H+ through H-ATPase

Answer 209

Inulin is fully filtered and not re-absorbed or secreted by the tubules. The tubular fluid/plasma tubular concentration can assess water re-absorption.

Answer 210

Filtration = Kf x (Pc – Pif - πc +πif) - Hydrostatic pressure inside the tubular capillaries (Pc) - Hydrostatic pressure in the interstitial fluid (Pif) - Colloid Osmotic Pressure in the Tubular Capillaries (πc) - Colloid Osmotic pressure in the interstitial fluid (πif) This is opposite to the forces allowing filtration across the glomerulus. Ie high capillary pressure, less re-absorbtion and vice versa. High colloid oncotic pressure in the tubules -> decrease filtration

Answer 211

peritubular capillary hydrostatic pressure - Increase in arterial pressure tend to raise peritubular capillary hydrostatic pressure - Increase in resistance of the afferent or efferent arterioles reduces peritubular capillary hydrostatic pressure (increases in the glomerulus but not the plasma oncotic osmotic pressure nfluenced by the systemic plasma oncotic osmotic pressure and the filtration fraction across the glomerulus. The higher the filtration fraction, meaning the more concentrated the remainder of the plasma remains the strongest the plasma oncotic pressure

Answer 212

This is the same as natriuresis. I.e. a small increase in arterial blood pressure will increase urinary excretion of Na and water. However, it only mildly increases GFR; it mainly raises urine output through increased tubular fluid load, where the increase in interstitial hydrostatic pressure increases the back look of Na into the tubular lumen. Additionally, increased BP results in a decrease in angiotensin II formation and therefore aldosterone production and Na conservation (this is because the macula dense detects NaCl in the urine and therefore downregulates renin)

Answer 213

Aldosterone -> principal cells of collecting ducts where it upregulates Na:KATPase, ROMK and ENaC AngII 1) Increases aldostereone 2) constricts efferent arteriole decreasing hydrostatic pressure in the peritubular capillaries promoting NaCl reabsorbtion 3) ANGII stimulates the Na/K ATPase, H:Na and H:HCO3 channels in the proximal tubule, loop of henle, distal tubules and collecting ducts Antidiuretic Hormone (vasopressin) 1) increased AQP-2 gene expression -> increased aquaporin II receptors -> increase H2O absorbtion Atrial natriuretic peptide Cardiac stretch -> release of granules containing ANP -> ANP downregulates renin and directly inhibit Na reabsorbtion PTH and calcitonin Binds to PTH and calcitonin receptors bind PTHR1 receptors increasing Ca reabsorbtion and decreasing phosphorous reabsorbtion

Answer 214

ADH. When osmolarity of the plasma increase above normal (e.g., dehydration) – the posterior pituitary gland secretes more ADH which will increase the permeability of the distal tubule and collecting duct to water. This mechanism increases water re-absorption and concentrate urine When osmolarity of the plasma decrease below normal (e.g., overhydration) – the posterior pituitary gland inhibits ADH secretion which will decrease the permeability of the distal tubule and collecting duct to water. This mechanism decreases water reabsorption and dilute urine. This is key as it allows the kidneys to secrete more water without changing the amount of solutes excreted (osmolarity will change obv as more fluid is ecreted)

Answer 215

proximal tubules (ISOSMOTIC)– water and solutes are reabsorbed proportionally. As fluid flow into the descending loop of Henle water is reabsorbed by osmosis until the osmolarity of the interstitial medulla and tubular space equilibrate. Ascending loop of Henle (HYPOSMOLAR) – in the thick segment of the ascending loop of Henle solutes are avidly reabsorbed. However, the cells of the thick ascending loop of Henle are impermeable to water (even in the presence of ADH). This causes the tubular fluid to become more dilute: the distal tubular segment become hypo-osmotic. Distal and colleting duct (VARIABLE) – in the absence of ADH the distal tubule and collecting duct are impermeable to water. Further NaCl is reabsorbed which dilute water further. Large amount of urine is excreted

Answer 216

for urine concentration you need high ADH, and you need hyperosmotic adrenal medulla. The countercurrent multiplier mechanism is what keeps the medulla hyperosmotic. This is due to the anatomical arrangement of the loop of the henle and vasa recta (specialised peritubular capillaries that are found in the medulla). Additionally, the juxtaglomerular nephrons have deep loops of henle that dive deep into the medulla and are intertwined with the vasa recta

Answer 217

much higher than other part of the body: 1,200 -1,400 mOsm/L compared to (300 mOsm/L corrected to 283 mOsm/L). this is due to; 1) Active transport of sodium ions and co-transport of potassium, chloride and other ions out of the thick portion of the ascending loop of Henle 2) Active transport of ions from the collecting duct into the medullary interstitium 3) Facilitated diffusion of urea from the inner medullary collecting duct in the medullary interstitium 4) Diffusion of only small amounts of water from the medullary tubules into the medullary interstitium-far less than the reabsorption of solutes into the medullary interstitium

Answer 218

This is due to the countercurrent mechanism, partially caused by the the medulla which has been made very hypersmolar by the thick ascending loop which is not permeable to water and actively pumps solutes out of the urnine.

Answer 219

When tubular fluid reaches distal convoluted tubules, it has an osmolarity of only 100-140 mOsm/L. There is further re-absorption of NaCl which will further dilute the fluid. In the presence of ADH, the distal tubule and collecting duct become permeable to water which causes rapid reabsorption of water into the intersitium which is quickly taken up by the capillaries of the vasa recta. Most of the reabsorption occurs in the cortical collecting duct which helps preserve the high medullary interstitial fluid osmolarity.

Answer 220

Urea contributes 40-50% of the osmolarity of the renal medullary interstitium. It is passively re-absorbed from the tubules. As water flow into the ascending loop of Henle, distal convoluted tubules and cortical collecting duct, there is little reabsorption of urea because these segments are impermeable to urea. In the presence of ADH, water is reabsorbed which increases urea concentration further. When urea reaches the medullary collecting tubules it diffuses into the interstitium down it’s concentration gradient through UT-A1 and UT-A3 transporters. These receptors are activated by ADH meaning that under increased water reabsorption there is increased urea reabsorption preventing decrease of osmolarity in the medulla.

Answer 221

AT-A1 and AT-A3, found in the medullary collecting tubules. These are bound by ADH which increases urea re-absorbtion which leads to water re-absorbtion. AT-A2 receptors secrete urea, and are found in the thin loop henle. These help urine uptake H20

Answer 222

Proximal tubules - Osmolarity similar to plasma (isosmotic to plasma) - Re-absorb 65% of solutes present in tubular fluids. - Membrane is highly permeable to water due to presence of aquaporin -1 channels (AQP-1) Descending loop of Henle - Osmolarity is higher than plasma (hypertonic to plasma) - Permeable to water due to AQP-1 channels and semi-permeable to solutes which means that the osmolarity progressively increase as the descending arm dives deeper and deeper into the medulla. - Osmolarity can be lowered indirectly by ADH due to decrease urea absorption from the collecting duct. Thin ascending loop of Henle - Osmolarity is higher than plasma (hypertonic to plasma) - Virtually impermeable to water. - Passive diffusion of solutes into the interstitium will lower osmolarity Thick ascending loop of Henle - Osmolarity is lower than plasma (hypotonic to plasma) - Virtually impermeable to water. - Active transport of solutes (Na+, Cl- and K+) into the interstitium which markedly decrease the osmolarity of the tubular fluid Early distal convoluted tubules – similar property to thick ascending loop of Henle - Osmolarity is lower than plasma (hypotonic to plasma) - Virtually impermeable to water. - Active transport of solutes (Na+, Cl- and K+) into the interstitium which markedly decrease the osmolarity of the tubular fluid Late distal tubule and cortical collecting duct {ADH dependent} - In high ADH concentration: Highly permeable to water. Water is reabsorbed into the interstitium. - Semi-impermeable to Urea allowing it to reach the medullary collecting duct -In Low ADH concentration: Impermeable to water Hypotonic to plasma Inner medullar collecting duct {ADH dependent} - In High ADH concentration: Highly permeable to water. Water flows into the interstitium until equilibrium has been reached which produce small amount of highly concentrated urine. - `The medulla becomes highly permeable to urea due to activation of UT-A1 and UT-A3 transporters.

Answer 223

Increased osmolarity, less blood volume -> osmoreceptors in the anterior hypothalamus shrink -> fire action potentials when they shrinking -> AP travels down to posterior pituitary -> ADH released -> travels to distal tubule +cortical collecting duct + medullary collecting duct -> increase AQP2 transcription -> increase Aquaporin 2 receptors -> water re-absorbtion

Answer 224

Osmoreceptors of the anterior hypothalamus -> neurohypophysis supraoptic neurons (large volume) ->neurohypophysis Paraventricular neurons (minor volume) -> neurohypophysis

Answer 225

1) arterial baroreceptor reflex 2) cardiopulmonary reflex These relay signals to the hypothalamus in response to decreased arterial blood pressure and/or decreased blood volume (atria, aortic arch and carotid sinus)

Answer 226

Osmoreceptors - 1% molarity change will result in ADH upregulation Blood volume/Bp require a 10% decrease in blood volume for an ADH release response

Answer 227

↑ plasma osmolarity ↓ blood volume ↓ blood pressure Nausea Hypoxia Drugs (e.g., morphine, nicotine, cyclophosphamide)

Answer 228

↓ plasma osmolarity ↑ blood volume ↑ blood pressure Drugs (e.g., alcohol, etc…)

Answer 229

Many mechanisms which increase ADH will also stimulate thirst. The supraoptic nuclei has a thirst center which induces stimuli via; 1) increase plasma osmolality -> causes intracellular dehydration activating thirst center (2mEg/L increase in [Na] is enough to trigger this) 2) Decrease in blood volume and arterial blood pressure 3) angiotensin II secretion 4) dryness of the mouth, mucous membrane and oesophagous 5) gastrointestinal and pahryngeal stimuli

Answer 230

They do not, as they use Na to upregulate water absorption. This, as a result does not increase the overall Na concentration as the water is "diluting this out"

Answer 231

All cells are a store. After a meal, K is rapidly uptaken to prevent the K from causing side effects. The kidneys are the major secretors w

Answer 232

- Insulin (lets Glucose into the cell which will then let K surge in) - Aldosterone - ß-adrenergic stimulation - alkalosis

Answer 233

- K deficiency - Aldosterone deficiency (addisons) - ß blockade - Acidosis - Cell lysis - Strenous exercise

Answer 234

Insulin stimulates the Na:KATPase, increasing Na retention and insulin excretion. In people with diabetes we can see a rise in K after each meal because the Na:KATPase pumps are not activated due to the lack of or the insulin resistance.

Answer 235

Because there is a lack of aldosterone (mineralocorticoid) production which means there is no stimulus for the collecting ducts to increase ROMK and Na:KATPase mediated secretion of K

Answer 236

Increased epinepherine release stimulates ß2 receptors. These increase Na:KATPase function (drawing K into the cells). It does this via adenylate cyclase. ß-blockers may cause hypokalaemia becasuse of this

Answer 237

Usually; - Acidosis = increase K extracellular - Alkylosis = decrease K extracellular We do not know for sure why, but we suspect its due to the fact that H+ downregulates Na:KATPase

Answer 238

65% proximal tubule 25-30% loop of Henle.

Answer 239

Principal cells of the collecting duct - Na:KATPase activity increased which brings more K into the principal cell - ROMK (renal outer medullary potassium channels) - BK (Big potassium channel) Potassium can also be reabsorbed by type A intercalated cells in the distal tubule and collecting duct

Answer 240

causes hypokalaemia

Answer 241

The flow rate in the tubule can be high enough that the K level is not detected as elevated as it "flows away too quickly". This can occur after a meal, in the presence of fluid volume expansion, Na intake increase (e.g. food), or certain diuretics

Answer 242

Ca is not secreted! Only filtered. Only the ionized form (non ionized secreted into the faeces) can be filtered, and under normal circumstances the majority is re-absorbed -65% proximal tubule - 35% loop of henle - 10% collecting duct

Answer 243

Proximal tubule - 80% paracellular - 20% transcellular via CaATPase, Ca:Na counter current chanel Loop of henle - Paracellular 50% - Trancellular 50% - regulated by PTH binding PTHR1R -> urpregulats TRPV5

Answer 244

↓ PTH ↑ Extracellular volume ↑ Blood pressure ↓ Plasma phosphate concentration Metabolic acidosis

Answer 245

↑ PTH ↓ Extracellular fluid volume ↓ Blood pressure ↑ Plasma phosphate concentration Metabolic alkalosis 1,25 Vitamin D3

Answer 246

Mainly due to overflow mechanism; renal tubules can reabsorb phosphate at around 0.1 mmol/minute. When Pi glomerular filtrate is above threshold there is net secretion of Pi and virtually all is re-absorbed When glomerular Pi secretion is above threshold then virtually all is secreted. 75-80% of Pi is reabsorbed in the proximal tubule . PTH increases doenregulates Pi re-absorbtion

Answer 247

↓ dietary phosphate 1,25- vitamin D3 Metabolic alkalosis Thyroid hormone

Answer 248

Thyroid hormones, esp T3, increases the expression of sodium-phosphate cotransporters (NaPi-IIa and NaPi-IIc) in the proximal tubule of the kidney.

Answer 249

↑ Dietary phosphate Parathyroid phosphate Metabolic acidosis Hypertension

Answer 250

Macula densa feedback in which increased NaCl delivery cause afferent arteriolar constriction and return to normal GFR. This works in conjunction with Pressure natriuresis and pressure diuresis maintain body sodium and fluid balance

Answer 251

- Constriction in the renal arterioles, which decrease GFR - Increase in tubular re-absorption of Na+ and water - Release of renin, which activates the RAAS system

Answer 252

heart disease Preganancy Volume overload (chronic

Answer 253

Liver cirrhosis -> leads to accumulation of fluid through both decrease oncotic pressure and portal hypertension Nephrotic syndrome-> loss of proteins, cause interstitial oedema and can cause hypovolemia leading to RAAS and sympathetic nervous activation

Answer 254

Upregulates 1) Reduced Na to the convoluted tubule at the level of the macula densa 2) Reduced systemic BP - baroreceptors 3) Sympathetic stimulation Inhibits 1) Atrial natriuretic peptide

Answer 255

Cardiovascular - AG2 bind AT1 increasing SVR Neuroal; - hypothalamus -> stimulat thirst - Posterior pituitary gland -> produces ADH stimulating body to concerve water and concentrate urine - Sympathetic nn; AG2 increases CO, vasocostriction of arterioles, release of renin Adrenal stimulates increased expression of CYP11B2 in the glomerulosa to produce Aldosterone.

Answer 256

7.4 (technically 7.4 for arterial and 7.35 for venous due to the extra CO2)

Answer 257

1) Chemical acid-base buffer systems of body fluids; which immediately combine H+ with a base to prevent change in pH Acts in seconds 2) The respiratory center (lungs); control the removal rate of CO2 (H2CO3) from the body Acts in minutes 3) The kidneys which can secrete either alkaline or acidic urine depending on the body’s need. Take several hours but more powerful

Answer 258

Bicarbonate consists of a watery solution, a weak acid H2CO3, and a bicarbonate salt such as NaHCO3. H2CO3 can be formed spontaneously in the body; however, the reaction is slow, a special enzyme: carbonic anhydrase drives the following reaction: H2O + CO2 ⇔ H2CO3. This enzyme exists in large concentration in the lung alveoli and in the renal tubular epithelium. H2CO3 will ionize weakly: H2CO3⇔ H+ + HCO3- 3 main roles are; - Secretion of H+ - Re-absorption of HCO3- - Generation of New HCO3-

Answer 259

It is not an important extracellular fluid buffer but does play a role in buffering tubular fluid and intracellular fluid. The main elements of the phosphate buffer system are H2PO4- and HPO42- If a strong acid is added to the system: HCl + HPO42- ⇔ H2PO4- ⇔ NaH2PO4 + NaCl. The net outcome is the generation of a weak acid and the decrease in pH is essentially minimized. If a strong base is added to the system: NaOH + H2PO4- ⇔ HPO42- + H20 ⇔ 2NaHPO4 + H2O the strong base was traded for a weak base Na2HPO4 which only raises the pH slightly.

Answer 260

xtremely important in the tubular fluid of the kidney for two reasons: 1. Phosphate become highly concentrated in the tubule thereby increasing the buffering power of this system 2. The tubular fluid usually has considerably lower pH to the extracellular fluid The phosphate buffer system is important intracellularly for similar reasons as described above

Answer 261

Proteins are plentiful buffer in the body and represent around 60-70% of the body total buffering capacity; however, H+ and HCO3- diffuse slowly across cell membranes which means that it may take hour for this system to reach equilibrium. Red blood cells are the exception as they equilibriate instantaneously with their environment and use hemoglobin as a strong buffering agent.

Answer 262

control of the respiration which effectively control CO2 concentration in the extracellular fluid. By increasing ventilation, CO2 is eliminated from extracellular fluid, which by mass action, reduces concentration of H+. The pulmonary expiration of CO2 will balance the metabolic formation of CO2 H2O + CO2 ⇔ H2CO3⇔ H+ + HCO3- + Na

Answer 263

Note that impaired lung function can cause respiratory acidosis. If the lung function is impaired, the CO2 cannot be eliminated from the body, which drives the following equation toward the right: H2O + CO2 ⇔ H2CO3⇔ H+ + HCO3- + Na+ causing respiratory acidosis. If this happens, the kidney will be the only organ system in the body that can control acid-base balance

Answer 264

80-90% of HCO3- reabsorption and H+ secretion-> proximal tubules. Minor re-absorption in the thick ascending loop of Henle, distal tubule and collecting duct. HCO3- to be re-absorbed, a proton (H+) must be secreted through the tubular space

Answer 265

PRoximal tubule; Na+/H+ exchanger (lumen) pumps H out -> reabsorbs 95% of HCO3. This can only reduce urine pH to 6.7. HCO3- re-absorption through the collecting tubules and duct which allows the urine pH to drop as low as 4.2. H+ will react with HCO3- in the tubular lumen to form H2CO3 which will then dissociate to CO2 and H2O to be re-absorbed into the tubular cells. There a carbonic anhydrase recreates H2CO3 to be dissociated again to form HCO3. This then uses the Na/HCO3 symporter distal and collecting tubules and through the rest of the tract use primary active transport to remove H+. This occurs in the type A intercalated cells - H+ / ATPase pump - H+/K+ ATPase pump

Answer 266

When there is excess H+ secreted in the tubular lumen, the phosphate buffer system will use ammonia to generate new HCO3-. H+ is secreted into the tubular lumen; however, once HCO3- from the tubular lumen is depleted, the H+ will combine with HPO4- and another tubular buffer to be excreted as a sodium salt NaH2PO4 carrying the excess H

Answer 267

Ammonium ions are generated from glutamine which arise from the metabolism of amino acids in the liver and transported into the tubular epithelium. Then each molecule of glutamine is transform into 2 ammonium ions (NH4+) and two bicarbonate (HCO3-). The ammonium is secreted into the tubular lumen for Na+ via a counter current mechanism. amonia passively diffuse into the tubular lumen in which it combine with H+ and becomes NH4+ which can no longer cross back in the tubular cells.

Answer 268

An increase in H+ will upregulate glutamine generation by the liver which will increase excretion of NH4+ and generation of additional HCO3- by the kidneys. In chronic acidosis this system becomes the primary means to get rid of excess H+ and produce new HCO3-

Answer 269

In Alkalosis: the tubular excretion of H+ is so low that not all the HCO3- flowing through the tubule is reabsorbed leading to a net excretion of HCO3- n this state, there is no titrable acid and ammonia (NH4) excreted as there is not enough H+ however In Acidosis: the tubular excretion of H+ is high enough that all of the HCO3- filtered is re-absorbed. In addition, the excess H+ are excreted as titratable acid and NH4 which lead to the production of additional HCO3-

Answer 270

Tubular injury reduced alpha-1-hydroxylase, so the synthesis of vitamin D is reduced = less calcium absorbtion from the gut Less GFR means less phosphorous excretion and therefore more in the blood. This binds to free calcium reducing availability. Both these result in hypocalcaemia leading to hyperparathyroidism

Answer 271

Damage to tubular cells reduces EPO production, and therefore, stimulus to produce RBC. It also produces inflammatory interlinking (IL-6 and IL-1) you get increased hepsidin acute inflammatory protein from the liver. Increased hepsidin controls ferroprotein in the GIT and release of iron from the macrophages. When this is high it shuts down iron release from the macrophages and absolution from the GIT so you get low iron anemia too

Answer 272

increase in ventilation causes a decrease in Pc02, which lead to decrease H+ in the system and HCO3-; As a result there is decreased H+ flowing through the tubular system which prevent re-absorption of filtered HCO3- and leads to net excretion of HCO3

Answer 273

There is a rise in plasma HCO3- and rise in pH. The compensatory mechanisms include a respiratory acidosis and an increase HCO3- excretion by the kidneys

Answer 274

(1) failure of the kidneys to excrete normally formed H+, (2) formation of excess quantities of metabolic acid by the body, (3) addition of metabolic acid to the body by ingestion, (4) loss of base from body fluids which has the same effect as adding H+ to the body.

Answer 275

Renal tubular acidosis - Mechanism (1): defect in H+ secretion - Mechanism (2): defect in HCO3- reabsorption Caused by underlying tubular disease (e.g., chronic renal failure, insufficient aldosterone secretion, or Fanconi syndrome) Diarrhea - Loss of large amount of HCO3 in the feces Vomiting of intestinal contents (not gastric content will result in a loss of bicarbonate). Diabetes mellitus - The reliance on free fatty acid metabolism leads to accumulation of highly acidic ketone bodies. Ingestion of acids Chronic renal failure

Answer 276

Administration of diuretics - All diuretics have the net effects of increasing tubular flow which leads to increase Na+ re-absorption which is coupled to H+ secretion, which leads to net H+ excretion Excess aldosterone – as we discussed aldosterone will trigger the intercalated cells of the distal tubules to secrete additional H+ Vomiting of gastric contents - vomiting of gastric content will lead to the loss of vast amounts of HCl. (Remember foreign body obstruction: metabolic alkalosis with hyponatremia and hypochloremia)

Answer 277

compensated respiratory acidosis includes decreased pH, increased PC02, and slightly above-normal HCO3- compensated metabolic acidosis includes a decreased pH, decreased PC02, and decreased HCO3-

Answer 278

when there is decreased bicarb, high PCO2 and low pH

Answer 279

Plasma anions gap = [Na+] – [HCO3-] – [Cl-] The concentration of anions and cations in the plasma must be equal to maintain electrical neutrality. There is no real ions gap in the plasma; however, only certain ions can be measured on routine chemistry: Na+ , Cl- and HCO3-. The ion gap will arise if unmeasured anions rise or unmeasured cations fall. The ion gap will be used as a diagnostic tool to differentiate different causes of metabolic acidosis

Answer 280

If there is a metabolic acidosis, HCO3- is decreased and there is no change in Cl- concentration, there must be an increase in the unmeasured ions (increased anion gap) which is normochloremic metabolic acidosis Diabetes mellitus (DKA) Lactic Acidosis Chronic renal failure Aspirin poisoning Methanol poisoning Ethylene glycol poisoning Starvation

Answer 281

If there is a metabolic acidosis, HCO3- is reduced, therefore if the plasma concentration Na+ remains constant Cl- and unmeasured anions increase to maintain electrical neutrality. This is referred to as a normal anion gap (hyperchloremic metabolic acidosis) Diarrhea Renal tubular acidosis Carbonic anhydrase inhibitors Addison disease

Answer 282

Mechanism of action: inhibit sodium reabsorption and potassium excretion These are also potassium sparing diuretics. Site of action: collecting tubules

Answer 283

Conditions that damage the glomeruli capillaries or other small vessels E.g; vasculitis, malignant hypertension, cholesterol emboli, acute glomerulonephritis Conditions that damage the renal tubular epithelium e.g. acute tubular necrosis due to ischemia, acute tubular necrosis due to toxins (e.g heavy metal tox, ethylene glycol, aminoglycosides) Conditions that damage renal interstitium e.g. acute pyelonephritis

Answer 284

type of intra-renal cause of AKI caused by abnormal immune complex deposition in the glomerulus. It is a classical type III hypersensitivity reaction occuring somewhere in the body. Antibodies and white blood cells become entrapped in the glomerulus causing inflammation and damage

Answer 285

destruction of the epithelial cells in the tubules. Common cause of tubular necrosis include: severe ischemia with inadequate supply of oxygen to the tubular cells and poisons (toxins or medications) which destroy the tubular cells. -> Severe renal ischemia can result from shocks, sepsis or any disturbances that prevent oxygen delivery to the kidney. If this happens the necrotic tubular cells will essentially “plug” the nephrons, which means they will fail to secrete urine. Usually, the most common causes of tubular necrosis through ischemia are pre-renal causes of AKI -> Toxic injury to the tubules – there are a long list of poisons that may cause injury to the tubular cells

Answer 286

Retention of water, waste product of metabolism, and electrolytes. - Hyperkalemia - Metabolic acidosis

Answer 287

Chronic kidney disease is defined as the presence of kidney damage or decreased kidney function that persist for at least 3 months. CKD is often associated with progressive and loss of large numbers of functioning nephrons. The clinical signs (azotemia) do not begin to appear until 70-75% of nephrons have been lost.

Answer 288

Interstitial nephritis After an initial damage, the remaining nephrons will undergo adaptive changes to ↑ GFR & urine output of surviving nephrons. These changes are poorly understood but involve: - Hypertrophy - Vasodilation Eventually these compensatory change leads to glomerular sclerosis which leads to further decrease in the nephron number, more adaptive changes, and lead to a vicious cycle. Eventually, the cycle leads to end-stage renal disease where the remaining nephrons can no longer maintain renal homeostasis.

Answer 289

1. Hypoalbuminemia 2. Proteinuria 3.Hypercholesterolemia 4. Ascites or fluid accumulation This is feature is pathognomonic for glomerular disease. The cause of this syndrome will be increase in permeability of the glomerular membrane. Common glomerular disease which can give rise to nephrotic syndrome include: Chronic glomerulonephritis Renal amyloidosis Glomerular sclerosis

Answer 290

Phosphate and hydrogen ions do not start to rise in the plasma until GFR has fallen below 20-30 % of normal. Maintenance of this solutes in the plasma at relatively constant rate is due to to the remaining nephrons decreasing the rate or re-absorption or, in some cases, increasing the rate of secretion.

Answer 291

n the case of Sodium and Chloride, the value remains constant even with severe impairment to GFR as the surviving nephrons will increase their excretion and re-absorption of these solutes.

Answer 292

As more and more nephrons are lost, the kidneys loose the ability to concentrate or dilute urine; this is because the increase hypertrophy and blood flow to the remaining nephrons leads to the following: Rapid flow of tubular fluid through the remaining collecting duct prevents adequate water re-absorption Rapid flow of fluid through the loop of henle prevents the counter current mechanism to concentrate the medulla necessary for fluid re-absorption

Answer 293

Renal lesions that decrease kidney ability to excrete sodium and water will promote hypertension. - Increase renal vascular resistance, which reduce renal blood flow and GFR (e.g., renal arterial sclerosis) - Decrease glomerular filtration coefficient (glomerular sclerosis) - Excessive tubular sodium reabsorption; excessive aldosterone secretion

Answer 294

blood glucose concentration may be normal; however, there is a defect in the tubular mechanism for glucose re-absorption which leads to failure of the kidneys to reabsorb glucose. - e.g. Fanconi

Answer 295

this condition the kidneys fail to re-absorb amino acids General aminoaciduria; is a rare condition where the kidneys fail to re-absorb all amino acids More frequently, the kidneys can present with deficiencies in specific amino acids reabsorption - Essential cystinuria; excretion of cystine amino acids which eventually leads to the formation of crystals (breed predisposition: Newfound land) - Simple glycinuria - Beta- aminoisobutyricaciduria

Answer 296

failure of the kidney to respond to anti-diuretic hormones. In veterinary medicine, esp. in pyometra enterotoxic e.coli will bind to the receptor causing a transient DI.

Answer 297

Strenuous exercise, seizures, fever, exposure to extreme heat or cold, and stress. Excessive consumption can also cause a transient spike

Answer 298

involve the production of low-molecular-weight proteins (dysproteinemias) that are filtered by the glomeruli and subsequently overwhelm the reabsorptive capacity of the proximal tubule e.g. Bence Jones proteins secodnary to myeloma, or proteins from inflammation of the urinary tract such as cystitis etc

Answer 299

Changes observed in the urine sediment usually are compatible with the underlying inflammation (e.g., pyuria, hematuria, bacteriuria, and increased numbers of transitional epithelial cells).

Answer 300

cysto (remove the risk of downstream inflammation contaminating sample). Spin down the sample and look for casts, cellular debris, WBC, etc. Proteinuria is truly diagnosed when present on 3 separate sample taken two or more weeks apart

Answer 301

UPC and immunoassay for albuminuria that are expressed either as albumin/creatinine ratios or in mg/dl. Most studies have shown that normal urine protein excretion in dogs and cats is 10 mg/kg or less per 24 hours and that normal UP/C ratios are 0.2 or less. UP/C values between 0.2 and 0.5 in dogs and between 0.2 and 0.4 in cats are considered borderline. Persistent proteinuria that results in a UP/C ratio of more than 0.4 and 0.5 in cats and dogs, respectively, for which prerenal and postrenal proteinuria. have been ruled out, is consistent with either glomerular or tubulointerstitial CKD. UP/C ratios above 2.0 are strongly suggestive of glomerular disease

Answer 302

depends on whether there is azotemia or not. Nonazotemic, persistently proteinuric patients, further investigation and appropriate treatment of potential concurrent infectious, inflammatory disorders, or neoplastic diseases is warranted. Persistent proteinuria/albuminuria with no identifiable underlying cause and no azotemia treat UP/C ratios of more than 1.0 to 2.0 In azotemic dogs and cats, treat UP/C ratio is 0.5 and 0.4 or higher, respectively. Recomendations; - reduce dietary protein - omega 3 faty acid - ACEi

Answer 303

Usually specific clinical signs. Proteinuria (i.e., a urine protein/creatinine [UP/C] ratio >0.5, however, these usaully have greater protein loss. UPC >2 is consistent with glomerular DZ. Identification of a cuasue is helpful as several inflammatory, neoplastic and auto-immune conditions can cause this. Renal biopsy is required to determine the specific histologic subtype of glomerular disease. Note; If injury to renal tubules develops at a slower rate than does the glomerular injury, some renal concentrating ability may persist despite development of azotemia

Answer 304

In a subset of dogs and cats with glomerular disease, hypoalbuminemia and proteinuria are accompanied by hypercholesterolemia and extravascular fluid accumulation, referred to as nephrotic syndrome.

Answer 305

Animals with International Renal Interest Society (IRIS) stage 1 or 2 (and possibly stage 3) chronic kidney disease that have UP/C values in or nearing the nephrotic range suggested in people likely will benefit most

Answer 306

Angiotensin-converting enzyme (ACE) inhibitors angiotensin II type 1 receptor blockers (ARBs) aldosterone receptor antagonists inhibit the renin- angiotensin-aldosterone system (RAAS) reatment of dogs with glo- merular diseases with enalapril significantly reduces pro- teinuria and delays onset or progression of azotemia and therefore is considered a standard of care K binder (Kayexalate) maybe needed or deeding a reduced potassium diet

Answer 307

deposition of immune complexes on the subepithelial glomerular basement membrane surface (may be found in the mesangium) in patients with secondary MG. Deposition of sub- epithelial immune complexes results in podocyte injury and foot process effacement, with eventual thickening of the glomerular basement membrane. If a cause is not identified, immunosuppressive therapy may be warranted in nonazotemic. No consensus on TX - in people, response can be seen with corticosteroids combined with an alkylating agent.

Answer 308

Nephrotic syndrome resulting in fluid accumulation and edema is a consequence of severe proteinuria. - removal of free fluid -> take off what is needed to resolve symptoms otherwise more volume and protein is lost. - RAAS inhibitors/ARB inhibitors/ANGII inhibitors -> if these are only partially successfull at treating proteinuria, low dose diuretics maye needed. Use of intravenous colloids is not recommended in patients with nephrotic syndrome unless they require immediate increases in intravascular oncotic pressure to prevent or minimize life-threatening fluid accumulation (patients often get workse oedema and ascities with this)

Answer 309

Concurrent azotemia appears to be a negative prognostic indicator; median survival of nonazotemic nonnephrotic dogs with glomerular disease is 605 days, versus 45 days for azotemic nonnephrotic dogs with glo- merular disease

Answer 310

COX-2 is the isoenzyme that con- tributes to renal inflammation, COX-2 is expressed constitutively in the kidney, is important in the control of renal blood flow and glomerular filtration rate, is up-regulated in volume depletion and in both inflamma- tory and noninflammatory forms of CKD, and contrib- utes to the viability of renal tubular and interstitial cells The COX-1 isoenzyme is expressed constitutively too in the canine collecting duct cells, medullary interstitial cells, endothelial cells, and smooth muscle cells of the preglo- merular and postglomerular vessels. Critically, the COX-2 isoform has a wider constitutive distribution in the canine kidney and is present in the canine glomerulus, loop of Henle, macula densa, renal interstitial cells, and blood vessels.

Answer 311

1) intiation 2) extension 3) maintance 4) Recovery First 2 stages often last <48h and may not be associated with clinical signs or blood work changes The third stage, main- tenance, is characterized by azotemia, uremia, or both and may last for days to weeks. Oliguria. Marked polyuria may occur during 4th stage as a result of partial restoration of renal tubular function and osmotic diuresis of accumulated solutes.

Answer 312

Maintenance fluid requirements (44 to 66 ml/kg/day) must be met and estimated fluid losses from vomiting or diarrhea replaced. Urine production should be monitored during the first few hours of fluid therapy. Placement of an indwelling urinary catheter is the most accurate method for such monitoring.

Answer 313

Idea was to increase GFR and excretion of toxin, however, high fluid rates have been shown to not be associated with faster toxin clearance

Answer 314

- Assess hydration and volume status -> physical examination of hydration status, visual estimation of jugular venous pressure, measurement of packed cell volume and total solids, thoracic radiography to evaluate cardiac size and pulmonary vascular mark- ings, and ultrasonographic imaging of the cardiac cham- bers and hepatic veins - If circulating blood volume is normal or increased, the rate of fluid administration should be slowed to prevent fluid overload - An indwelling urinary catheter should be placed if not already present. - calculate urine output and include esti- mated at 22 ml/kg/day for insensible losses q4h - Specific therapy to increase urine flow, consisting of administration of one or more diuretics, should be instituted next (furosemide 2mg/kg with escalation to 4-6mg/kg boluses at hourly intervals if UOP does not increase -> CRI more effectine - Mannitol - controversial - Mannitol may have addi- tional beneficial effects in addition to its action as a diuretic. It inhibits renin release because of its hyperos- molar effect on tubular luminal filtrate. Mannitol also acts as a free-radical scavenger, blunting damaging increases in intramitochondrial calcium, and may result in a beneficial release of atrial natriuretic peptide

Answer 315

Staging is based initially on fasting blood creatinine or fasting blood SDMA concentration or (preferably) both assessed on at least two occasions in a hydrated, stable patient. The dog or cat is then substaged based on proteinuria and blood pressure

Answer 316

I; - Dog CREA - SDMA = <1.4 <18 - Cat CREA - SDMA = < 1.6 <18 Some other renal abnormality present (such as, inadequate urinary concentrating ability without identifiable non-renal cause (in cats not dogs), abnormal renal palpation or renal imaging findings, proteinuria of renal origin, abnormal renal biopsy results, increasing blood creatinine or SDMA concentrations in samples collected serially). Persistently elevated blood SDMA concentration (>14 μg/dl) may be used to diagnose early CKD II; - Dog CREA - SDMA = 1.4-2.8 18-35 - Cat CREA - SDMA = 1.6-2.8 18-25 Clinical signs usually mild or absent III; - Dog CREA - SDMA= 2.9 - 5 36-54 - Cat CREA - SDMA= 2.9 - 5 26-38 Many extrarenal signs may be present, but their extent and severity may vary. If signs are absent, the case could be considered as early Stage 3, while presence of many or marked systemic signs might justify classification as late Stage 3. IV; - Dog CREA - SDMA= >5.0 >54 - Cat CREA - SDMA= 5.0 >38 Increasing risk of systemic clinical signs and uremic crises

Answer 317

If serum or plasma SDMA is persistently >18 μg/dl in a dog whose creatinine is <1.4 mg/dl (IRIS CKD stage 1 based on creatinine), this canine patient should be staged and treated as an IRIS CKD Stage 2 patient. If serum or plasma SDMA is persistently >35 μg/dl in a dog whose creatinine is between 1.4 and 2.8 mg/dl (IRIS CKD stage 2 based on creatinine), this canine patient should be staged and treated as an IRIS CKD Stage 3 patient. If serum or plasma SDMA is persistently >54 μg/dl in a dog whose creatinine is between 2.9 and 5.0 mg/dl (IRIS CKD stage 3 based on creatinine), this canine patient should be staged and treated as an IRIS CKD Stage 4 patient. ## Footnote If crea is in a lower stage than the SDMA and the SDMA is persistently elevated in that stage thn you need to upstage the IRIS grade

Answer 318

Same as dogs. If Crea is in one stage, but SDMA is persistently high and in a stage higher than that of the creatinine then we upscale

Answer 319

Healthy Birman cats and greyhound dogs have been found to have higher serum SDMA values than other breeds. Both these breeds also have higher serum creatinine values taking some healthy individuals (up to 20% of Birman cats) outside laboratory reference intervals

Answer 320

Substaging by proteinuria and hypertension. 1) proteinuria The goal is to identify renal proteinuria having ruled out post-renal and pre-renal causes. UP/c value - Dog <0.2, Cat <0.2 = non-proteinuric - Dog 0.2-0.5, cat 0.2-0.4 = borderline proteinuric - Dog >0.5, cat >0.4 = proteinuric Canine and feline patients that are persistently borderline proteinuric should be re-evaluated within 2 months and re-classified as appropriate. 2) Hypertension (EDO = end organ damage) <140 - normotensive - minimal EOD 140-159 - prehypertensive - low EOD 160-179 - hypertensive - moderate EOD ≥180 sverely hypertensive - high EOD

Answer 321

- Standard urine dipsticks can give rise to false positives More specific available screening include; - UP/C - Species-specific albuminuria assay The UP/C should be measured in all dogs and cats with CKD, provided there is no evidence of urinary tract inflammation or hemorrhage and the routine measurement of plasma proteins has ruled out dysproteinemias. Dipstick will also have false positives from these isues. Albuminuria assey less so, butt his is also uncommonly performed.

Answer 322

U P/Cs in the non-proteinuric or borderline proteinuric range may be categorized as ‘microalbuminuric’. The significance of microalbuminuria in predicting future renal health is not completely understood at present. IRIS’ recommendation is to continue to monitor this level of proteinuria (dogs). Veterinarians might offer treatment for cats persistently in the borderline proteinuric or microalbuminuric range considering the association with proteinuria of this level and progressive kidney disease in the cat

Answer 323

Proteinuria may decline as renal dysfunction worsens and so may be less frequent in dogs and cats in Stages 3 and 4. Or Treatment for proteinuria maybe effective - this should be monitored with regular UP/c testing

Answer 324

Hypertensive – systolic blood pressure 160 to 179 mm Hg measured over 1 to 2 weeks Severely hypertensive – systolic blood pressure ≥180 mm Hg measured over 1 to 2 weeks.

Answer 325

he stage and substages assigned to the patient should be revised appropriately as changes occur. For example, a substantial increase in blood creatinine or SDMA concentration might warrant reassignment to a higher stage to reflect the new situation. Similarly, if antihypertensive (or antiproteinuric) treatment has been instituted, the patient’s classification on re-evaluation should be adjusted if necessary to reflect the new blood pressure (or UP/C) rather than the original status, with the addition of an indication that the current classification is affected by treatment.

Answer 326

Classification – IRIS CKD Stage 2, borderline proteinuric, severely hypertensive post treatment New classification – IRIS CKD Stage 2, non-proteinuric, prehypertensive (treating)

Answer 327

Discrepancies between creatinine and SDMA section, if blood SDMA is persistently >35 μg/dl in a canine patient whose blood creatinine is between 1.4 and 2.8 mg/dl (IRIS CKD stage 2 based on creatinine), this dog should be staged and treated as an IRIS CKD Stage 3 patient Post tratment RIS CKD Stage 3, borderline proteinuric (treating), prehypertensive

Answer 328

Grade I CREA <1.6 a) documented AKI -> historical, clinical lab or imaging evidence of AKI, clinical oliguria/anuria, volume responsiveness, and or; b) progressive, non azotemic increase in CREA >0.3mg/dl within 48h c) measured oliguria (<1ml/kg/h) or anuria over 6h Grade II Crea 1.7-2.5mg/dl a) mild aki and stati or progressive azotemia b) progressive azotemic: crea ≥0.3 within 48 or volume respoinsiveness c) measured oliguria (<1ml/kg/h) or anuria over 6h Grade III Crea 2.6-5.0 Grade IV Crea 5.1-10 Grade V Crea >10 With grade III, IV and V, these are moderate to severe AKI -> increasing severity associated with unctional failiure

Answer 329

Grade 1->5 with; NO = non oliguric O= oliguric And if RTT is aded theat menas requiring renal replacement therapy