Renal Flashcards

1
Q

Name major kidney functions

A
  1. Regulation of systemic blood pressure and extracellular fluid volume
  2. Excretion of metabolic waste and foreign substances
  3. Regulation of RBC production
  4. Regulation of acid-base balance
  5. Regulation of Vit. D production and Ca2+/Ph balance
  6. Gluconeogenesis
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2
Q

In which 2 major ways do kidneys regulate systemic blood pressure?

A

1) Determining blood volume -> controls cardiac output
2) Making hormones that regulate the vascular resistance

SBP = CO x VR

CO = heart rate x stroke volume

Stroke volume = end diastolic volume - end systolic volume

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3
Q

What are uremic retention solutes or uremic toxins

A

Urea (from proteins)
Uric acid (from nucleic acids)
Creatinine (from muscle creatine)
Urobilin (end product of hemoglobin)

If they are not excreted and plasma levels increase -> uremia

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4
Q

Where is erythropoietin produced during embryological development? and in the adults?

A

Liver
Kidneys

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5
Q

Stimulus to secrete erythropoietin

A

Reduction in partial pressure of oxygen in the local environment of the secreting cells.

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6
Q

Conditions that stimulate EPO secretion

A

Anemia
Blood loss
Arterial hypoxia
Inadequate renal blood flow

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7
Q

Why does anemia of chronic renal disease happens

A

1) Renal metabolism falls -> lower oxygen consumption -> higher local tissue oxygenation.

2) This “fools” the EPO-secreting cells into diminished EPO secretion.

3) Decrease in bone marrow activity - one important causal factor of the anemia.

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8
Q

T/F - Most gluconeogenesis occurs in the liver, but a substantial fraction occurs in the kidneys, particularly during a prolonged fast

A

TRUE

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9
Q

What does penetrate the renal hilum

A

Blood vessels
Nerves
Ureters

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10
Q

Describe the major structural components of the kidney

A
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11
Q

T/F - Pyramids collectively constitute the medulla

A

TRUE

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12
Q

What are cortex and medulla constructed off?

A

Almost entirely of tubules (nephrons and collecting tubules) and blood vessels.

Between the tubules and blood vessels -> interstitium, <10% of renal volume.

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13
Q

What does the renal interstitium contains?

A

Interstitial fluid
Interstitial cells -> fibroblasts and immune cells -> synthesize a matrix of collagen, proteoglycans, glycoproteins and cytokines.
Some of these cells synthesize EPO.
Lymphatics.

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14
Q

Types of nephrons

A

85% of nephrons - cortical -> glomeruli located in the outer cortex. Short LOH, only penetrates into the outer renal medulla. Reduced vasa recta.

15% of nephrons -> juxtamedullary -> glomeruli near the corticomedullary border. LOH extents deep into the renal medulla. Large network of vasa recta. Provides blood flow to renal medulla.

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15
Q

Where are the renal corpuscules located

A

Renal cortex

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16
Q

T/F - The cortex contains renal corpuscles, coiled blood vessels and coiled tubules. The medulla contains straight blood vessels and straight tubules.

A

TRUE

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17
Q

Draw / describe a nephron

A
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18
Q

Components of renal corpuscule

A

Bowman’s capsule - epithelial cells
Renal glomerulus - tuft of capillary loops

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19
Q

Draw / describe the structure of the renal corpuscle

A
  • Bowman’s capsule - epithelium
  • Glomerulus -> tuft of capillaries -> afferent arteriole brings blood in, efferent drains blood out.
  • Mesangial cells and podocytes -> in close association with the capillary loops of the glomerulus.
  • Mesangial cells -> act as phagocytes, remove trapped material from the basement membrane of the capillaries.
  • Podocytes -> support structure, important role in glomerular filtration.
  • Bowman’s space -> where fluid filters from the glomerular capillaries before flowing into the first portion of the tubule.
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20
Q

T/F - Throughout the whole length, the renal tubule is made up of a single layer of epithelial cells resting on a basement membrane.

A

TRUE.

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21
Q

How are the epithelial cells linked together in the renal tubules?

A

Via tight junctions

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22
Q

Name the renal tubular segments

A
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23
Q

Describe the structure of the nephron and where each part falls in relationship with cortex / medulla structure

A
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24
Q

Is the urine altered once it enters a calyx?

A

No

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25
Q

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

A

TRUE

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26
Q

T/F - Thick ascending limbs of LOH do not begin at the same level

A

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

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27
Q

What marks the end of the thick ascending limb of the LOH and beginning of distal convoluted tubule?

A

The macula densa

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28
Q

What is different in the epithelial cells of the distal convoluted tubule?

A
  • Up to the DCT, the epithelial cells forming the wall of a nephron in any given segment are homogeneous and distinct for that segment.
  • In the DCT -> the epithelium contains 2 types of cells:
    • Principal cells -> majority
    • Intercalated cells -> intercalated between principal cells.
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29
Q

Role of JGA

A

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

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30
Q

Type of cells in the JGA

A

1) Granular cells -> differentiated smooth muscle cells in the walls of the afferent arterioles. They contain secretory vesicles with renin inside.

2) Extraglomerular mesangial cells - a continuum with the glomerular mesangial cells but outside the Bowman’s capsule (BC).

3) Macula densa cells - detect flow rate and composition of fluid within the nephron at the very end of the thick ascending limb -> control renin secretion.

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31
Q

Basic renal processes

A

Filtration
Secretion
Reabsorption
Excretion

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32
Q

Filtration

A

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

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33
Q

Composition of glomerular filtrate (within bowman’s capsule)

A
  • Very much like blood plasma
  • Contains very little proteins -> large proteins are not filtrated.
  • Inorganic ions and LMW organic solutes in same concentration as plasma.
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34
Q

What is the glomerular filtration rate. Normal values in healthy adult young male?

A

The volume of filtrate formed per unit of time.
125mL/min (180L/day -> all other capillaries of the body, approx. 4L/day).

Average total volume of plasma in humans: 3L -> entire plasma volume is filtered 60 times / day.

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35
Q

Secretion

A

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

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36
Q

Reabsorption

A

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

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37
Q

T/F Most of the tubular transport consists on reabsorption rather than secretion

A

TRUE

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38
Q

T/F - Reabsorption of waste products is partial, so that large fractions of the filtered amounts can be excreted in urine.

A

TRUE

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39
Q

T/F - Reabsoprtion of most “useful” plasma components is either complete or nearly so, so that very little is excreted in urine

A

TRUE

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40
Q

Amount filtered per day, amount excreted and % reabsorbed of water, Na, Glucose and urea

A
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41
Q

What are the main metabolic processes performed by tubular cells?

A
  • They extract nutrients and metabolize them as dictated by the cell’s own nutrient requirements.
  • They also do other metabolic transformations directed toward altering the composition of urine/plasma.
  • Most important:
    • Gluconeogenesis
    • Synthesis of ammonium from glutamine
    • Production of bicarbonate
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42
Q

What are the main mechanisms to regulate renal processes

A
  • Neuronal signals -> originate in the sympathetic celiac plexus.
  • Hormonal signals -> from adrenal gland, pituitary, parathyroid and heart.
  • Intrarenal chemical messengers - originate in one part of the kidney and act in another part -> NO, superoxide, eicosanoids… also influence basic renal processes.
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43
Q

How much % of the CO kidneys receive?

A

About 20% of the resting CO

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44
Q

Where is the blood flow to the kidneys delivered?

A

To the cortex.

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

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45
Q

Describe the renal blood flow

A
  • Blood enters each kidney at the hilum via a renal artery
  • After several divisions into smaller arteries blood reaches arcuate arteries that course across the tops of the pyramids between the medulla and cortex.
  • From these, interlobular arteries (also called cortical radial arteries) project upward toward the kidney surface.
  • These arteries give off numerous arterioles, each of which leads to an individual Bowman’s capsule and the glomerulus within.
  • These arteries and glomeruli are found only in the cortex, never in the medulla.
  • The arterioles leading to glomeruli are called afferent arterioles and have important functional characteristics discussed later.
  • In most organs, capillaries recombine to form the beginnings of the venous system, but the glomerular capillaries instead recombine to form another set of arterioles, the efferent arterioles.
  • The vast majority of the efferent arterioles soon subdivide into a second set of capillaries called peritubular capillaries / vasa recta.
  • These capillaries are widely distributed throughout the cortex in close proximity to the tubular segments.
  • The peritubular capillaries then rejoin to form the veins by which blood ultimately leaves the kidney.
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46
Q

The resistance of any single vessel is a function of

A
  • Blood viscosity
  • Vessel length
  • Vessel RADIUS -> see formulas, Poiseuille’s law
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47
Q

Why is Poiseuille’s law important?

A

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

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48
Q

T/F Most of the times, resistance of afferent and efferent arterioles are about equal and account for most of the total renal vascular resistance

A

TRUE

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49
Q

Where is hydrostatic pressure higher, in the glomerular capillaries or in the peritubular capillaries?

A

In the glomerular capillaries.

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

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50
Q

How can changes in resistance of the afferent / efferent arterioles affect GFR?

A
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51
Q

T/F The sites with higher vascular resistance is where larger blood pressure drops occur

A

TRUE

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52
Q

Describe structure of the glomerular filtration barrier

A

1) Endothelial cells of the capillaries, is perforated by many large fenestrae, which occupy about 10% of the endothelial surface area. They are freely permeable to everything in the blood except red blood cells and platelets. 60-80nm.

2) The middle layer, the capillary basement membrane, is a gel-like acellular meshwork of glycoproteins and proteoglycans, with a structure like a kitchen sponge. It has negative charges, repelling negatively charged molecules (like albumin).

3) The third layer consists of epithelial cells (podocytes) that surround the capillaries and rest on the capillary basement membrane. The podocytes have an unusual octopus-like structure. Arms extend from the soma and wrap around several nearby glomerular capillaries. Small “fingers,” called pedicels (or foot processes), extend from each arm and are embedded in the basement membrane. The spaces between the pedicels, called slits, are the passageway through which the glomerular filtrate passes. The pedicels are coated by a thick layer of extracellular material, which partially occludes the slits. 30-40nm.

4) Finally, extremely thin processes called slit diaphragms bridge the slits between the pedicels.

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53
Q

What is the selectivity of the filtration barrier based on?

A

Molecular size
Electrical charge

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54
Q

Substances with molecular weight less than ________ can move easily through the filtration barrier

A

7000Da

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55
Q

The filtration barrier excludes molecules bigger than ________

A

70,000 Da

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56
Q

T/F For any given size, negatively charged macromolecules are filtered to a greater extent, and positively charged macromolecules to a lesser extent, than neutral molecules

A

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

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57
Q

T/F The negative charges in the filtration membrane it is a hindrance only to macromolecules, not to mineral anions or LMW organic anions -> chloride and bicarbonate are freely filtered despite their negative charge

A

TRUE

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58
Q

The glomerular basement membrane is extremely negatively charged due to

A

Heparin sulfate on the lamina rara interna and externa

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59
Q

Examples of substances that can filtrate through the glomerular filtration barrier

A

1) Electrolytes: HCO3–, Na+, K+, Cl–, Ca2+, Mg2+, H2O
* Despite the negative charge on some of these electrolytes, they’re very small; hence, they will get freely filtered

2) Non-negatively charged low-molecular weight molecules: glucose, amino acids, lipids, urea, creatinine, vitamins.

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60
Q

What is the main component of the slit diaphragm?

A

Nephrin

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61
Q

Components of the net filtration pressure

A
  • Glomerular hydrostatic pressure GHP
  • Colloid osmotic pressure COP
  • Capsular hydrostatic pressure CHP
  • Capsular oncotic pressure CoP

These are known as the Starling forces

NFP = (forces that want to push out) - (forces that want to push in)
NFP = (GHP + CoP) - (COP + CHP)
NFP = (55 + 0) - (30 + 15) = 10mmHg

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62
Q

Glomerular hydrostatic pressure

A

1) Force that pushes plasma out of the glomerular capsule into the bowman’s space

2) Directly dependent on systolic blood pressure
High BP = High GHP
Low BP = Low GHP

3) Average value: 55 mmHg

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63
Q

Colloid osmotic pressure

A
  • Exerted by plasma proteins like albumin
  • Keeps water in the blood
  • Average value: 30 mmHg

Clinical Correlates:
• Multiple myeloma: increases amount of proteins in blood -> holds on to more water in the blood -> increases COP.

• Hypoproteinemia -> loses substances/proteins -> can’t hold on to water as much -> decreases COP.

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64
Q

Capsular hydrostatic pressure

A

As fluid is being filtered out, the pressure will push things back into the capillary bed
* By the pressure build-up in the Bowman’s capsule
* Average value: 15 mmHg

Clinical Correlate:
• Renal calculi
o Kidney stone stuck in nephron
o > 5mm in diameter
o Pressure backs up and starts increasing -> increases CHP

• Hydronephrosis
o Due to renal ptosis
o Rapid weight loss
o Increased CHP -> more fluid being pushed back into the glomeruli and not much glomerular filtration.

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65
Q

Capsular osmotic pressure

A

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

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66
Q

Glomerular filtration rate

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

GFR = NFP x Kf

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67
Q

T/F The hydrostatic pressure is nearly constant within the glomeruli but the oncotic pressure in the glomerular capillaries does change substantially along the length of the glomeruli

A

TRUE

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68
Q

Explain why the oncotic pressure in the glomeruli changes

A

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

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69
Q

An increase in afferent arteriole resistance will increase or decrease glomerular pressure?

A

Decrease

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70
Q

An increase in efferent arteriolar resistance will increase or decrease glomerular pressure?

A

Increase

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71
Q

Dilation of the afferent arteriole

A

Raises glomerular pressure and hence GFR

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72
Q

Dilation of the efferent arteriole

A

Decreases glomerular pressure and GFR

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73
Q

T/F Kidneys can regulate glomerular pressure and hence GFR, independently of renal blood flow

A

TRUE

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74
Q

Anything that increases glomerular oncotic pressure tends to ___________ net filtration pressure and hence GFR

A

Decrease

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75
Q

If renal blood flow is low, what will happen to the oncotic pressure? And in high renal blood flow conditions?

A

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

2) With high renal blood flow -> glomerular oncotic pressure will increase less than normal -> higher NFP -> higher GFR

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76
Q

Renal plasma flow and filtration fraction

A

RPF = the flow of plasma through the glomeruli

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

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77
Q

T/F The increase in glomerular oncotic pressure along the glomerular capillaries is directly proportional to the filtration fraction

A

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

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78
Q

What causes most often changes in the filtration coeficient? (Kf)

A

Glomerular diseases

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79
Q

Major cause of decreased GFR in aging / renal disease

A

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

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80
Q

What is filtered load?

A

The amount of substance filtered per unit of time.

For freely filtered substances, that is the product of GFR x plasma concentration of that substance.

Na+ for example:
Plasma: 140mEq/L = 0.14mEq/mL
Normal GFR = 125mL/min
Na+ filtered load = 0.14 x 125 = 17.5mEq/min.

What is presented to the rest of the nephron to handle!

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81
Q

Why are glomerular capillaries more sensitives to hypertension than capillaries in other parts of the body?

A

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

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82
Q

What is the most important of the factors that tends to change GFR?

A

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

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83
Q

T/F - Autoregulation prevents large changes in GFR in the face of changes in arterial pressure

A

TRUE

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84
Q

Via which mechanism can the kidney modify the renal blood flow and urine output?

A

Intrinsic mechanisms:
* Myogenic mechanism
* Tubuloglomerular feedback

Extrisinc mechanisms:
* Sympathetic NS
* RAAS - Renin - angiotensin - aldosterone - ADH system

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85
Q

Intrinsic myogenic mechanism when blood pressure increases

A

↑BP → ↑GHP → ↑GFR -> higher glomerular filtration rate (GFR), more urine.

Kidneys modulate the GFR so that it is not too excessive making too much urine, or the blood pressure does not remain too high causing injury on the glomerular capillaries.

Myogenic response -> blood flows through the afferent arteriole (AA) then to the efferent arteriole (EA) -> ↑BP = more blood to the AA -> Na channels in the smooth muscle of the afferent arteriole are sensitive to stretch -> AA vasoconstricts → ↓glomerular blood flow (GBF) → ↓filtered plasma and other substance (↓GFR)

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86
Q

Intrinsic myogenic mechanism when blood pressure decreases

A

↓BP → ↓GHP → ↓GFR
↓BP = ↓urine = can cause kidney injury -> how does the kidney prevent it?

Mechanism:
↓BP => ↓blood to the AA -> ↓stretch on the AA -> ↓stretch therefore less Na+ enter in the smooth muscle cell → less positive charge → ↓Ca2+ released by the sarcoplasmic reticulum → less contraction => relaxation.

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87
Q

Summary of intrinsic myogenic mechanism

A

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

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

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88
Q

Tubuloglomerular feedback with increased BP

A

This mechanism is sensitive to NaCl -> NaCl gets reabsorbed in the proximal convoluted tubule (PCT).

1) ↑BP = ↑GFR = ↑NaCl excretion into the kidney tubules

2) When NaCl transporters in the PCT are saturated, NaCl can escape and move to the LH and then to the DCT where macula densa cells are found
o Special NaCl sensors
o Release adenosine when it detects ↑NaCl

3) Adenosine functions to:
o Vasoconstrict AA → ↓GBF → ↓GFR → ↓NaCl being filtered
o Inhibit juxtaglomerular (JG) cells → ↓renin → ↓blood pressure

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89
Q

Tubuloglomerular feedback with decreased BP

A

↓BP = ↓GFR = ↓NaCl excretion into the kidney tubules
When macula densa cells detect ↓NaCl in DCT, they release PGI2 and nitric oxide (NO)

PGI2 and NO function:
o Vasodilate the AA → ↑GBF → ↑GFR → ↑NaCl filtered
o Stimulates juxtaglomerular (JG) cells → increases renin release → increases blood pressure

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90
Q

Summary of tubuloglomerular feedback

A

↑BP = ↑GFR = ↑NaCl filtered
o ↑NaCl detected by MD cells → release adenosine → vasoconstricts AA and inhibits JG cells to release renin.

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

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91
Q

Extrinsic mechanism - sympathetic nervous system

A

1) Stimulus: ↓↓↓SBP → MAP < 65 mmHg
o MAP (mean arterial pressure): measure of perfusion
o When MAP < 65 mmHg, kidney is not perfused; blood flow is redirected to other “more important” organs such as the heart, brain and muscles.

↓BP → ↓GFR → ↓urine output
o ↓blood flow can cause kidney injury
o SNS do its best to increase blood flow

MECHANISM:
1) ↓BP triggers baroreceptors → CN IX and CN X send less signals to the medulla oblongata (vasomotor center)

2) Vasomotor center activates sympathetic nerve fibers in the thoracic part causing release of NE and epinephrine, that will act in different systems:

a) Heart

NE and epi stimulate the β1 receptors in the nodal system and contractile fibers → ↑HR and ↑SV (due to ↑contractility) respectively → ↑CO → ↑BP -> to increase blood flow in the kidneys to avoid injury.

Chronotropic: change in heart rate / Ionotropic: change in contractility

b) Renal afferent and efferent arterioles -> NE and EPI will act on the α1 receptors of the AA and EA → vasoconstriction → ↓GBF → ↓GFR

YES, the goal is to increase the blood flow towards the kidney BUT in sympathetic crisis, the SNS DOES NOT respect the kidneys

c) Systemic vessels -> NE and EPI act on the α1 receptors on the systemic vessels → vasoconstriction of multiple vessels → ↑systemic vascular resistance (SVR) → ↑BP

d) Juxtoglomerular Cells -> NE and EPI stimulate the β1 receptors on the JG cells → ↑renin → activates angiotensin II →→→ ↑BP

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92
Q

Summary of SNS effects when BP is low

A

Increase HR and SV
Vasoconstriction of the renal afferent and efferent arterioles
Vasoconstriction of the systemic vessels → ↑SVR
Triggers release of renin from the JGA

The effects are the exact opposite when the blood pressure is HIGH.

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93
Q

Extrinsic mechanism - Initiation of RAAS to produce ATII

A

1) ↓BP → ↓GFR

2) Juxtoglomerular cells are sensitive to changes in blood pressure -> when BP is low, JG cells release renin.

3) Renin cleaves angiotensinogen to produce angiotensin I

4) Angiotensin I move to the capillaries in the lungs and get converted to angiotensin II by angiotensin converting enzyme (ACE).

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94
Q

Extrinsic mechanism - ATII functions - RAAS

A

1) ADH Release -> stimulates the hypothalamus that trigger release of ADH from the pituitary gland.

ADH (aka vasopressin or antidiuretic hormone) -> acts on the aquaporin in the collecting duct to reabsorb water -> ↑H2O in blood → ↑blood volume → ↑BP

2) ↑Thirst -> makes you thirsty → ↑water intake → ↑blood volume → ↑BP

3) Aldosterone release -> stimulates release of aldosterone from the zona glomerulosa in the adrenal gland. Aldosterone -> acts on the DCT to make them permeable water and Na+ -> ↑Na+ and H2O reabsorption → ↑BV → ↑BP

4) Vasoconstriction of efferent arteriole and ↑GFR

Angiotensin II binds on the receptor on the EA → vasoconstriction of EA -> less blood can escape from the glomerulus, more blood stays in the glomerulus → more blood filtered out → ↑GFR

NOTE: Some books say that it also affects the AA; but the effect is much greater in EA (EA&raquo_space;> AA)

5) Angiotensin II also act on the PCT to cause increased reabsorption of Na+ and H2O -> ↑Na+ and H2O → ↑BV → ↑BP

6) Vasoconstriction of systemic vessels -> acts on systemic vessels → potent vasoconstriction → ↑SVR → ↑BP → ↑GFR

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95
Q

What happens when BP is increased?

A

In cases of HIGH BP, JG cells do NOT release renin. Therefore the RAAS does not occur.

Atrial natriuretic peptide -> released from the heart in cases of ↑BP and it can block any function of the angiotensin II:

a. Blocks ADH release = no water and Na+ reabsorption = urinate water and Na+ = ↓blood volume.

b. Blocks aldosterone release = no water and Na+ reabsorption = urinate water and Na+ = ↓blood volume

c. Prevents vasoconstriction of EA = ↓GFR

d. Causes vasodilation of blood vessels = ↓SVR = ↓BP

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96
Q

Summary of autoregulatory mechanisms

A
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97
Q

What is clearance

A

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

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98
Q

How can rate of removal be expressed?

A

2 ways:

Plasma half-life -> time it takes for the concentration of a substance in plasma to be reduced by 50%

Clearance -> measures the volume of plasma from which all of a substance is removed in a given time.

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99
Q

Renal clearance

A

The substance is removed from the plasma ONLY by the kidneys and is either excreted in urine or catabolized by the renal tubules.

The volume of plasma that needs to pass through the kidneys in a given amount of time in order to excrete a given quantity of a substance in the urine

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100
Q

T/F Assessing the renal clearance of certain substances that are not reabsorbed nor secreted by the nephron is very useful as it is an indicator of renal function

A

TRUE

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101
Q

T/F The utility on measuring renal clearance is to measure GFR

A

TRUE

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102
Q

Why is measuring GFR important?

A
  • Because the most commonly used marker of kidney disease (plasma creatinine concentrations) is not sensitive
  • Plasma creatinine concentrations do not increase until 75% of the nephrons are non functional.
  • Therefore GFR is much more sensitive.
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103
Q

Renal clearance equation

A
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104
Q

T/F If the clearance of a substance is higher than the GFR, there must have been net secretion

A

TRUE

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105
Q

T/F If the clearance of a substance is less than the GFR, there must have been net reabsorption

A

TRUE

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106
Q

What are the 3 approaches to quantify GFR using renal clearance?

A

1) Clearance of exogenous markers - inulin, radioactive markers, iohexol.

2) Clearance of endogenous markers - creatinine, cystatin C, urea.

3) Imaging of the kidneys -> renal scintigraphy, CT.

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107
Q

Gold standard of measuring GFR

A

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

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108
Q

Creatinine clearance

A

Practical and common
Low cost & convenient
Easier than inulin
Less invasive

Cr clearance is slightly higher than GFR (by 10% to 20%)

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109
Q

Cystatin C

A
  • Produced by all nucleated cells at a constant rate.
  • Only eliminated by kidneys.
  • All filtered cystatin is removed from the body (no reabsorption)
  • Production increases with large doses of corticoids.
  • Production affected by thyroid dysfunction and cancer.
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110
Q

Urea clearance

A
  • Less accurate indicator of GFR
  • Range of normal plasma urea concentrations varies widely depending on protein intake and changes in tissue catabolism.
  • Urea excretion is under partial hormonal regulation.
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111
Q

Urea clearance

A
  • Less accurate indicator of GFR
  • Range of normal plasma urea concentrations varies widely depending on protein intake and changes in tissue catabolism.
  • Urea excretion is under partial hormonal regulation.
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112
Q

Renal scintigraphy

A
  • Assesses function of each kidney separately
  • Inject a radiotracer in blood
  • Measure rise and fall of radioactive counts in each kidney separately
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113
Q

What are the differences in endothelium and interstitium between renal cortex and renal medulla?

A

Renal cortex:
Fenestrated vascular endothelium—noresistance to passive movement of water and small solutes.
Cortical interstitium (between basal membrane and endothelial cells)—similar osmolality and concentration of small solutes to plasma.

Renal medulla:
Only some fenestrated capillaries.
Medullary interstitium is not plasma-like.

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114
Q

How can substances cross the tubular epithelium?

A

Paracellular
Transcellular

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115
Q

Transcellular vs paracellular transport

A

Transcellular -> through cells -> in on one side, out at the other side

Paracelluar -> around cells through tight junctions

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116
Q

Mechanisms for substances to cross barriers

A
  • Diffusion - concentration gradient
  • Channels - pores that allow specific solutes to pass through
  • Transporters - allow passage of otherwise impermeable substances.
    • Simporters: 2 substances, same direction
    • Antiporter: 2 substances, opposite direction
    • Primary active transporters: require ATP, agains electrochemical gradient.
  • Receptor mediated endocytosis and transcytosis.
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117
Q

T/F - Blood flow and transport mechanisms are faster in the medulla compared to cortex

A

FALSE - faster in the renal cortex

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118
Q

What is selectivity

A

The ability to choose which substance is permitted to move

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119
Q

Its it only the cell membrane that is selective or also the tight junctions?

A

Both are selective

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120
Q

Family of proteins that are key for the tight junctions

A

Claudin

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121
Q

How is the permeability / expression of channels/transporters regulated?

A

1) Gated channels:
- Ligand - gated -> reversible binding of small molecules
- Voltage-gated -> changes in membrane potential
- Mechanical distorsion -> stretch gated.

2) Phosphorylation sites -> it can either open or close the channel

3) Some can be moved back and forth between the surface membrane and intracellular vesicles

4) Transcription and expression of channels regulated

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122
Q

Difference between a channel and a uniporter

A

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

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123
Q

How is normally called movement through an uniporter

A

Facilitated diffusion

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124
Q

T/F Symporters are also called cotransporters and antiporters, exchangers

A

TRUE

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125
Q

Key symporters (cotransporters) in the kidneys

A

Na-Glu
Na-K-2Cl

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126
Q

Key antiporters (exchangers) in the kidneys

A

Na+ / H+
Cl- / HCO3

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127
Q

Primary active transporters

A

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

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128
Q

Which transport mechanism is important in the host defense mechanisms of the kidney and in prevention of UTIs?

A

Transcytosis

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129
Q

Osmolarity

A

Volume of particles per liter of solvent (mol/L).

Generally, in the glomerulus, the blood is 300 mOsm/L

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130
Q

Proximal convoluted tubule I - tubular reabsorption (glucose, aa and lactate)

A

1) Sodium-Potassium ATPase -> 3 Na+ out and 2 K+ ions in.

  • Na+ and K+ move against their concentration gradient -> primary active transport -> requires ATP (97% of K in our bodies is inside the cell).

What does it do to the inside of the cell -> decreases Na and increases K.

2) Secondary active transport - passive diffusion of one substance helps facilitate the active transport of another substance (can transport two things at once inside the cell - cotransporter)

a) Sodium-glucose cotransporter -> since there’s low Na inside the cell, it’s moving passively along its concentration gradient. Glucose is high inside the cell -> Na+ helps glucose move against its concentration gradient. When it gets into the cell, there are specific transporters on the basolateral membrane that transports glucose out of the cell and into the bloodstream.

b) Sodium / amino acids Cotransporter -> transports Na+ inside the cell along with amino acids -> high concentration of amino acids inside the cell. Inside the cell, amino acids have specific transporters that facilitate their diffusion out of the tubular cell and into the blood.

c) Sodium-lactate Cotransporter -> passive diffusion of sodium facilitates transport of lactate

Assuming normal physiological conditions, 100% of the glucose, amino acids, and lactate get reabsorbed from the kidney tubules into the blood.

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131
Q

Proximal convoluted tubule - II - tubular reabsorption - bicarbonate.

A

How does bicarbonate (HCO3–) gets into the cell?

Via CO2 + H2O -> H2CO3 -> H+ + HCO3–

o CO2 -> can be found in our blood and can move into the cell (through the basolateral membrane) and react with water to form carbonic acid.

o Carbonic acid (H2CO3) -> unstable; dissociates into a proton (H+) and bicarbonate (HCO3–)

o What happens to the proton (H+) -> Sodium-hydrogen exchanger -> secondary active transport -> as Na+ moves through the channel to go in the cell, it helps push H+ out -> H+ combines with HCO3– outside of the cell -> H2CO3 is converted by carbonic anhydrase into CO2 and H2O in the lumen of the PCT.

o What happens to the bicarbonate (HCO3–)? -> approximately 90% of HCO3– gets pushed into the blood.

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132
Q

Proximal convoluted tubule - III - tubular reabsorption - bicarbonate reabsorption regulation

A

Regulation of reabsorption of filtered HCO3-

1) Filtered load -> increases in the filtered load of HC03- result in increased rates of HC03- reabsorption. However, if the plasma HC03- concentration becomes very high (e.g., metabolic alkalosis), the filtered load will exceed the reabsorptive capacity, and HC03- will be excreted in the urine.

2) PCO2
* Increases in PCO2 result in increased rates of HC03- reabsorption because the supply of intracellular H+ for secretion is increased. This mechanism is the basis for the renal compensation for respiratory acidosis.

  • Decreases in PCO2 result in decreased rates of HC03- reabsorption because the supply of intracellular H+ for secretion is decreased . This mechanism is the basis for the renal compensation for respiratory alkalosis.

3) ECF volume
ECF volume expansion results in decreased HC03 reabsorption.
ECF volume contraction results in increased HC03- reabsorption (contraction alkalosis).

4) Angiotensin II -> stimulates Na+-H+ exchange and thus increases HC03- reabsorption, contributing to the contraction alkalosis that occurs secondary to ECF volume contraction

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133
Q

Proximal convoluted tubule - IV - tubular reabsorption - water

A
  • Sodium is very critical in the process of OBLIGATORY WATER REABSORPTION -> when water is obliged to follow sodium (solutes) and move back into the blood.
  • For example, in the sodium-glucose channel -> when sodium is coming in with the glucose, water feels obliged to follow sodium -> water moves by the process of osmosis, from the kidney tubules into the blood.
  • About 65% of sodium is being reabsorbed, hence, 65% of water is also being reabsorbed.
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134
Q

Proximal convoluted tubule - V - tubular reabsorption - paracellular transport

A

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

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135
Q

Proximal convoluted tubule - VI - tubular reabsorption - Na/Cl cotransport

A

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

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136
Q

Proximal convoluted tubule - VII - tubular reabsorption - lipids

A

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

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137
Q

Proximal convoluted tubule - VIII - tubular reabsorption - small proteins (insulin, hemoglobin)

A
  • There are specific protein receptors on the membrane.
  • If these small proteins are filtered (normally they are not), they can get caught on these receptors
  • Proteins are endocytosed and taken into the cell, then combined inside the cell with lysozymes (hydrolytic enzymes that break down the proteins into their constituent amino acids). The vesicle then fuses with the cell membrane and amino acids are released into the blood
  • Receptors are recycled.
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138
Q

Proximal convoluted tubule - IX - sodium-phosphate cotransport

A
  • Cotransporter normally brings both Na+ and HPO42– into the cell.
  • There’s a receptor for the PTH on the basolateral membrane of the cells in the PCT.
  • PTH binds with the receptor and activates the G-stimulatory protein.
  • G-stimulatory protein activates adenylate cyclase, activating protein kinase A.
  • pkA phosphorylates the Na/phosphate cotransporter, inhibiting it.
  • Phosphates don’t get reabsorbed -> they get excreted.
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139
Q

Proximal convoluted tubule - summary of tubular reabsorption

A
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140
Q

Proximal convoluted tubule - compensation for metabolic acidosis

A

Glutamine is a specific type of amino acid -> it can undergo deamination, resulting into 2 ammonium ions (NH4+), and the acidified glutamine will be oxidized into 2 bicarbonate ions.

Normal blood pH is 7.35-7.45 -> in metabolic acidosis blood pH is low ( < 7.35), and the body has to compensate for that.

Bicarbonate resulting from the glutamine metabolism will be taken into the blood to bring the pH back up. In exchange, chloride ion will need to go out of the blood into the cell to maintain electroneutrality.

The ammonium ions also produced from the glutamine metabolism will be pushed out of the cell and into the kidney tubule -> it will dissociate into ammonia (NH3) and H+

  • REMEMBER - the other mechanism to reabsorb HCO3 and increase blood pH is via CO2 present in the blood and taken into the cells to be converted into H+ and HCO3 and the H+ secreted in the lumen in exchange for Na.
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141
Q

Proximal convoluted tubule - secretion

A

In the blood, there are certain things that we either reabsorb too much or we can’t get rid of - organic bases and acids, like certain drugs (penicillin, cephalosporins, methotrexate), and similar with uric acid, bile salts, morphine, those substances have to be secreted.

The process of getting these excreted into the kidney tubules is an active process -> requires ATP.

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142
Q

Loop of Henle - I how many parts does it have?

A

Two. Ascending limb and descending limb.

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143
Q

Loop of Henle - II - Osmolality values through the LOH

A
  • Inside the glomerulus: ~300 mosm -> is the blood plasma
  • In Bowman’s capsule: ~300 mosm -> sotonic with the blood plasma
  • When fluid leaves the PCT -> is still at 300 mosm -> it didn’t change because equal amounts of solutes and water were being reabsorbed (due to obligatory water reabsorption).
  • Medullary interstitial osmolality gets saltier or more hypertonic as we go down the renal medulla -> 300 mosm -> 500 mosm -> 700 mosm -> 900 mosm -> 1200 mosm
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144
Q

Loop of Henle - III - LOH - how does the medullary interstitium gets more hypertonic?

A

Na+/K+/2Cl– cotransporter:

  • Transports sodium, chloride, and potassium from lumen of filtrate into epithelial cell of ascending limb.
  • There are specific channels for each ion in the cell -> Na+ and Cl– will be pushed out (towards the medullary interstitium), increasing osmolality.
  • Only some of the K+ will pass to the interstitium, some of the K+ gets pushed back in the lumen. Creates depolarization of the inner side of the membrane of the ascending limb -> causes Mg2+ and Ca2+ to undergo paracellular transport.

IMPORTANT:
* The descending limb of loop of Henle is completely impermeable to solutes and permeable to water.

  • Exact opposite of the ascending limb which is only permeable to solutes, but impermeable to water.
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145
Q

Loop of Henle - IV - LOH - what happens due to the salty medullary interstitial space?

A

Counter-Current Multiplier Mechanism:

  • Water will flow out TO the area where the salt is -> from the descending limb to the ascending limb (due to obligatory water reabsorption).
  • Via Aquaporin-I -> always open in the descending limb of Loop of Henle
  • Since the medullary interstitial space is saltier as we go down, more water will leave as we go down the descending limb -> by the time the loop of Henle takes a turn to go up, its osmolality will be 1200 mosm -> becomes hypertonic as we move down.
  • When it goes up, however, the osmolality starts to go down because the ascending limb is losing salt -> by the time it reaches the Distal Convoluted Tubule (DCT) -> the osmolality will be around 120-200 mosm -> hypotonic compared to the plasma.
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146
Q

Loop of Henle - V - LOH - vasa recta

A
  • Peritubular capillary in the medulla, branching from the Efferent Arteriole
  • Known as the “Counter-Current Exchanger”
  • Plasma Osmolality Gradient in medullary interstitium -> 300 -> 500 -> 700 -> 900 -> 1200
  • Blood flow to vasa recta is really slow -> function: prevents rapid removal of sodium chloride
  • Does not develop the medullary interstitial gradient or the counter-current multiplier mechanism -> it’s maintaining the gradient; not generating it.
  • Vasa recta also delivers oxygen and nutrients.
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147
Q

Loop of Henle - summary

A

Descending Limb
o H2O permeable
o Solute impermeable
o Aquaporin-I - allows water to move out to the medullary interstitium

Ascending Limb
o H2O impermeable
o Solute permeable
o Na+/K+/2Cl– cotransporter -> pushes these solutes out into the medullary interstitium (salty; high osmolality) -> some K+ gets pushed back in the lumen, creating a depolarization on the inner side of the membrane of the ascending limb -> causes Mg2+ and Ca2+ to undergo paracellular transport.

Counter-Current Multiplier Mechanism
o Maintained by the vasa recta (vasa recta is the counter-current exchanger).

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148
Q

Distal convoluted tubule - I - early DCT - Na and Cl

A

1) Na-K Pump -> in basolateral membrane, requires ATP -> 3 Na+ ions out and 2 K+ ions in

2) Sodium-chloride symporter -> specialized transporters on the luminal membrane -> sodium and chloride both go into the cell.

* Since Na+ ions are going out via the Na-K pump, it means that DCT has high [Na+] compared to inside the cell (going against concentration gradient)
* Only 5-6% of Na+ is being reabsorbed here -> 4-5% is left
* Cl– will move in together with Na -> Cl- has a special channels in the basolateral mechanism that pumps it into the blood.
  • THIAZIDE * -> diuretic that inhibits sodium-chloride symporter -> it will affect both the salt and water reabsorption -> instead of reabsorbing the 5-6% back, you’ll lose them to the urine together with a bit of the blood volume
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149
Q

Distal convoluted tubule - II - early DCT - calcium reabsorption

A
  • When there are low blood calcium levels -> stimulate parathyroid gland to secrete PTH
  • PTH has a receptor on the cell of the distal convoluted tubule -> PTH binds and stimulates the receptor -> G stimulatory protein -> cAMP -> activates protein kinase A
  • pkA stimulates calcium modulated channels (very sensitive to PTH levels) via phosphorylation -> causes channels to pull in Ca2+ into the cell -> calcium can be bound to protein called calbindin inside the cell, but it will be a low percentage.
  • Even if blood calcium level is low, there’s still less calcium inside the cell compared to blood -> calcium will be moving against its concentration gradient. Two mechanisms to get calcium out

a) Ca2+/Na+ Transporter
• Proteins on the basolateral membrane
• Pumps calcium out and brings sodium in -> secondary active transport as Na goes down concentration gradient.

b) Ca2+/H+ transporter -> uses ATP -> calcium out, H+ in.

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150
Q

Distal convoluted tubule - III - late DCT - aldosterone

A
  • Generally impermeable to water.
  • Has specialized cells responsible for responding to aldosterone: principal cells -> responsible for mineral and water balance.
  • Aldosterone -> steroid hormone produced in the globular cells of the adrenal gland
  • Stimulus for aldosterone secretion: angiotensin-II (wants to increase pressure), hyponatremia and hyperkalemia. Small amounts of CRH can also stimulate its secretion.
  • Aldosterone passes through the cell’s lipid bilayer because it’s a steroid hormone -> it will activate specific transcription factors to produces different proteins:

1) ) Na channel -> protein embedded in the luminal membrane -> Na is allowed to go inside the cell due to the effects of the Na+/K+ Transporter (low intracellular Na)

2) Na+/K+ transporter in the basolateral membrane -> active transport, uses ATP. Puts 3 Na+ out of the cell, brings 2 K+ in.
Na+ would want to go from high concentration to low concentration -> Na+ goes inside the cell via the sodium channel
K+ enters the cell -> higher concentration in the cell

3) Potassium channel -> embedded in the luminal membrane -> since there’s high K+ inside the cell, the channel will move it out of the cell where it will eventually be excreted into the urine.

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151
Q

Distal convoluted tubule - IV - late DCT - ADH

A
  • Can act on the principal cells, together with aldosterone
  • Presence of ADH will open up the aquaporins-II
  • Water will have to follow the salt and go into the cell and into the bloodstream -> increases blood pressure.
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152
Q

Late DCT / Collecting duct - I - intercalated cells

A

o Maintain acid-base balance -> keep body within homeostatic range.

o Found in the late distal tubule and collecting duct.

o Intercalated A cells: acidic conditions.

o Intercalated B cells: basic conditions.

There are also other cells that could be secreting drugs: toxins, creatinine… and via the intercalated cells we will be secreting H+, HCO3-, ammonium…

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153
Q

Late DCT / Collecting duct - II - Intercalated A cells - acidosis

A

They respond to ACIDOSIS (metabolic or respiratory)

Scenario: there’s increased CO2 in the blood:
o In an acidosis, there is low pH = many protons.
o Very little bases to counteract the protons.

CO2 + H2O -> H2CO3 -> H+ + HCO3-

o Circulating carbon dioxide -> moves into the intercalate A cell, and combines with water to form carbonic acid (catalyzed by CA)

o Carbonic acid (H2CO3) -> unstable; dissociates into protons and HCO3–

o Protons (H+) -> there is an H+ / K+ ATPase in the luminal membrane -> K+ goes into the cell and H+ goes out, both against concentration gradient.

o Bicarbonate (HCO3–) -> will be pumped out of the cell into the blood via the HCO3–/Cl– transporter in the basolateral membrane.

o The body needs to secrete substances it doesn’t want, like ammonia (NH3) -> it can be excreted out into the urine where it will combine with the protons secreted to produce ammonium (NH4+).

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154
Q

Late DCT / Collecting duct - III - Intercalated B cells - alkalosis

A

Responds to ALKALOSIS (respiratory or metabolic)

The same pathway as intercalated-A cell, but flipped.
o Get rid of bicarbonate instead of the protons
o Reabsorb proton into the blood instead of bicarbonate

o Increased blood pH -> low H+ and high HCO3-

o CO2 + H2O -> H2CO3 -> H+ + HCO3-

o CO2 -> found in our blood -> moves into the intercalated B cell, and combines with water to form carbonic acid via CA -> carbonic acid -> unstable -> dissociates into protons and HCO3–

o HCO3– goes out of the cell -> pumped out of the cell into the urine via HCO3- / Cl- cotransporter -> Cl- goes into the cell in the luminal membrane via cotransporter and will exit the cell via the chloride channels on the basolateral membrane.

o Protons (H+) -> will be reabsorbed via H+ / K+ ATPase in the basolateral membrane (both ions are moving against their concentration gradients) -> K+ goes into the cell, H+ goes out of the cell into the bloodstream.

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155
Q

Late DCT / Collecting duct - IV - principal cells - ADH

A

Cells that maintain mineral and water balance

o Hypothalamus has a collection of neurons from the supraoptic nucleus
o Their axons move through from the hypothalamus to the posterior pituitary
o When stimulated, it will release ADH

o ADH will be released whenever the plasma osmolality is changing and can work in the late distal tubule and collecting duct. Second strong stimulus will be low blood volume (will cause the release of ATII -> will stimulate ADH release).

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156
Q

Collecting duct - V - principal cells - ADH

A

o ADH binds to the vasopressin receptor on the principal cell in the collecting duct of the kidneys -> adenylate cyclase -> activates pkA

o Phosphorylates the proteins on intracellular vesicles -> presynthesized vesicles with proteins and channels (aquaporins)

o Activates aquaporin-II -> vesicles fuses with the cell membrane

o There are aquaporin-III and aquaporin-IV in the basolateral membrane

o Water goes into the cell via aquaporin-II, then passes through aquaporins III & IV and goes into the blood -> increases blood volume, and increases blood pressure

o Also reaches normal plasma osmolality -> isotonic.

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157
Q

Urea recycling and medullary interstitium

A

o A lot of urea still gets lost in the urine, but some is recycled -> gets reabsorbed in the last part of the collecting duct.

o After all the water has been reabsorbed, urea starts increasing in the tubular lumen

o It then moves out of the collecting duct and into the medullary interstitium via facilitated diffusion (lipid soluble).

o It gets reabsorbed in the ascending limb of Loop of Henle and it also accumulates outside in the medullary interstitium.

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158
Q

Renal processess SUMMARY ALL

A
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159
Q

Total body water

A

60%

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160
Q

Distribution of body water and composition

A
  1. Intracellular fluid is two-thirds of TBW.
    The major cations of ICF are K+ and Mg.
    The major anions of ICF are protein and organic phosphates (ATP, ADP and AMP).
  2. Extracellular fluid is one-third of TBW and is composed of interstitial fluid + plasma.
    The major cation of ECF is Na+.
    The major anions of ECF are Cl- and HC03- .

a. Plasma is 25% (1/4) of the ECF. The major plasma proteins are albumin and globulins.

b. Interstitial fluid is 75% (3/4) of the ECF.
The composition of interstitial fluid is the same as that of plasma except that it has
little protein. Thus, interstitial fluid is an ultrafiltrate of plasma.

  1. 60-40-20 rule
    TBW is 60% of body weight.
    ICF is 40% of body weight.
    ECF is 20% of body weight.
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161
Q

Osmolarity

A

a. Osmolarity is concentration of solute particles.

b. Plasma osmolarity is estimated as:
Posm= 2 x Na + Glucose/18 + BUN/2.8 => mOsm/L

Na+ =plasma Na+ concentration (mEq/L)
Glucose = plasma glucose concentration (mg/dL)
BUN= blood urea nitrogen concentration (mg/dL)

c. At steady state, ECF osmolarity and ICF osmolarity are equal.

d. To achieve this equality, water shifts between the ECF and ICF compartments.

e. It is assumed that solutes such as NaCl and mannitol do not cross cell membranes and are confined to ECF.

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162
Q

Shift of water within compartments - adding isotonic fluid

A

Is also called isosmotic volume expansion.

1) ECF volume increases, but no change occurs in the osmolarity of ECF or ICF. Because osmolarity is unchanged, water does not shift between the ECF and ICF compartments.

2) Plasma protein concentration and hematocrit decrease because the addition of fluid to the ECF dilutes the protein and red blood cells (RBCs). Because ECF osmolarity is unchanged, the RBCs will not shrink or swell.

3) Arterial blood pressure increases because ECF volume increases.

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163
Q

Shift of water within compartments - loss of isotonic fluid

A

For example, diarrhea. Is also called isosmotic volume contraction.

1) ECF volume decreases, but no change occurs in the osmolarity of ECF or ICF. Because osmolarity is unchanged, water does not shift between the ECF and ICF compartments.

2) Plasma protein concentration and hematocrit increase because the loss of ECF concentrates the protein and RBCs. Because ECF osmolarity is unchanged, the RBCs will not shrink or swell.

3) Arterial blood pressure decreases because ECF volume decreases.

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164
Q

Shift of water within compartments - adding hypotonic fluid

A

SIADH - gain of water. Also called hypoosmotic volume expansion

1) The osmolarity of ECF decreases because excess water is retained.

2) ECF volume increases because of the water retention. Water shifts into the cells; as a result of this shift, ICF osmolarity decreases until it equals ECF osmolarity, and ICF volume increases.

3) Plasma protein concentration decreases because of the increase in ECF volume. Although hematocrit might also be expected to decrease, it remains unchanged because water shifts into the RBCs, increasing their volume and offsetting the dilut- ing effect of the gain of ECF volume.

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165
Q

Shift of water within compartments - loss of hypotonic fluid

A

Excessive sweat - also called hypertonic volume contraction

1) The osmolarity of ECF increases because sweat is hyposmotic (relatively more water than salt is lost).

2) ECF volume decreases because of the loss of volume in the sweat. Water shifts out of ICF; as a result of the shift, ICF osmolarity increases until it is equal to ECF osmolarity, and ICF volume decreases.

3) Plasma protein concentration increases because of the decrease in ECF volume. Although hematocrit might also be expected to increase, it remains unchanged because water shifts out of the RBCs, decreasing their volume and offsetting the concentrating effect of the decreased ECF volume.

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166
Q

Shift of water within compartments - adding hypertonic fluid

A

For example, excessive NaCl intake. Also called hypertonic volume expansion

1) The osmolarity of ECF increases because osmoles (NaCl) have been added to the ECF.

2) Water shifts from ICF to ECF. As a result of this shift, ICF osmolarity increases until it equals that of ECF.

3) As a result of the shift of water out of the cells, ECF volume increases (volume expansion) and ICF volume decreases.

4) Plasma protein concentration and hematocrit decrease because of the increase in ECF volume.

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167
Q

Shift of water within compartments - loss of hypertonic fluid

A

Adrenocortical insufficiency. Loss of NaCI. Is also called hyposmotic volume contraction.

1) The osmolarity of ECF decreases. As a result of the lack of aldosterone in adrenocortical insufficiency, there is decreased NaCl reabsorption, and the kidneys excrete more NaCl than water.

2) ECF volume decreases. Water shifts into the cells because ECF osmolarity decreases; as a result of this shift, ICF osmolarity decreases until it equals ECF osmolarity, and ICF volume increases.

3) Plasma protein concentration increases because of the decrease in ECF volume. Hematocrit increases because of the decreased ECF volume and because the RBCs swell as a result of water entry.

4) Arterial blood pressure decreases because of the decrease in ECF volume.

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168
Q

Clearance exercise - If the plasma [Na+] is 140 mEq/L, the urine [Na+] is 700 mEq/L, and the urine flow rate is 1 mL/min, what is the clearance of Na+?

A
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169
Q

T/F - RBF is directly proportional to the pressure difference between the renal artery and the renal vein and is inversely proportional to the resistance of the renal vasculature.

A

TRUE

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170
Q

T/F - Vasoconstriction of renal arterioles leads to a decrease in RBF

A

TRUE

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171
Q

Causes of vasoconstriction of renal arterioles

A
  • Produced by activation of the sympathetic nervous system and angiotensin II.
  • At low concentrations, angiotensin II preferentially constricts efferent arterioles, thereby “protecting” (increasing) the GFR.
  • Angiotensin-converting enzyme inhibitors dilate efferent arterioles and produce a decrease in GFR; these drugs reduce hyperfiltration and the occurrence of diabetic nephropathy in diabetes mellitus.
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172
Q

Causes of vasodilation of renal arterioles

A

Leads to an increase in RBF.

Is produced by prostaglandins E2 and I2, bradykinin, nitric oxide, and dopamine.

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173
Q

Effects of ANP on renal arterioles

A

Causes vasodilation of afferent arterioles and, to a lesser extent, vasoconstriction of efferent arterioles.

Overall increases RBF and GFR.

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174
Q

T/F Measurement of renal plasma flow (RPF) can be done with the clearance of PAH

A

TRUE

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175
Q

Formula RBF

A

RBF = RPF / (1-Ht)

Note that the denominator in this equation, 1 - hematocrit, is the fraction of blood
volume occupied by plasma.

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176
Q

Effect of changes in Starling forces on GFR, RPF and Filtration Fraction

A
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177
Q

T/F - Na+-glucose cotransport in the early proximal tubule reabsorbs glucose from tubular
fluid into the blood. There are a limited number of Na+-glucose transporters and they can get saturated.

A

TRUE

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178
Q

cAt plasma glucose concentrations greater than ______ mg/dL, the carriers are saturated

A

350mg/dL

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179
Q

Substances with the ________ (highest/lowest) clearances are those that are both filtered across the glomerular capillaries and secreted from the peritubular capillaries into urine (e.g., PAH).

A

Highest

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180
Q

Substances with the _______ (highest/lowest) clearances are those that either are not filtered (e.g., protein) or are filtered and subsequently reabsorbed into peritubular capillary blood (e.g., Na+, glucose, amino acids, HC03- , CI-).

A

Lowest

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181
Q

T/F - Substances with clearance equal to GFR are glomerular markers

A

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

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182
Q

Explain what happens with weak acids in urine

A

o weak acids have an HA form and an A- form.

o The HA form, which is uncharged and lipid soluble, can “back-diffuse” from urine to blood.

o The A- form, which is charged and not lipid soluble, cannot back-diffuse.

o At acidic urine pH, the HA form predominates, there is more back-diffusion, and there is decreased excretion of the weak acid.

o At alkaline urine pH, the A- form predominates, there is less back-diffusion, and there is increased excretion of the weak acid. For example, the excretion of salicylic acid (a weak acid) can be increased by alkalinizing the urine.

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183
Q

Explain what happens with weak bases in urine

A

o Weak bases have a BH+ form and a B form .

o The B form, which is uncharged and lipid soluble, can “back-diffuse” from urine to blood.

o The BH+ form, which is charged and not lipid soluble, cannot back-diffuse.

o At acidic urine pH, the BH+ form predominates, there is less back-diffusion, and there is increased excretion of the weak base. For example, the excretion of morphine (a weak base) can be increased by acidifying the urine.

o At alkaline urine pH, the B form predominates, there is more back-diffusion, and there is decreased excretion of the weak base.

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184
Q

TF/Px ratio - explain and examples

A
  • Tubular fluid (TF) is urine at any point along the nephron.
  • Plasma (P) is systemic plasma. It is considered to be constant.

TF/Px ratio compares the concentration of a substance in tubular fluid at any point along the
nephron with the concentration in plasma.

a. If TF/P= 1.0, then either there has been no reabsorption of the substance or reabsorption of the substance has been exactly proportional to the reabsorption of water.

For example, if TF/PN/ = 1.0, the [Na+] in tubular fluid is identical to the [Na+] in plasma.
For any freely filtered substance, TF/P = 1.0 in Bowman space (before any reabsorption or secretion has taken place to modify the tubular fluid).

b. If TF/P < 1.0, then reabsorption of the substance has been greater than the reabsorption of water and the concentration in tubular fluid is less than that in plasma.
For example, if TF/PNa+ = 8.0, then the [Na+] in tubular fluid is 80% of the [Na+] in plasma.

c. If TF/P >1.0, then either reabsorption of the substance has been less than the reabsorption of water or there has been secretion of the substance.

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185
Q

Na+ reabsorbption along the nephron

A
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186
Q

Explain the glomerulotubular balance in the proximal tubule

A

o Maintains constant fractional reabsorption (two-thirds, or 67%) of the filtered Na+
and H20.

1) For example, if GFR spontaneously increases, the filtered load of Na+ also increases. Without a change in reabsorption, this increase in GFR would lead to increased Na+ excretion.

2) However, glomerulotubular balance functions such that Na+ reabsorption also will increase, ensuring that a constant fraction is reabsorbed.

3) The mechanism of glomerulotubular balance is based on Starling forces in the peritubular capillaries, which alter the reabsorption of Na+ and H20 in the proximal tubule.

4) The route of isosmotic fluid reabsorption is from the lumen, to the proximal tubule cell, to the lateral intercellular space, and then to the peritubular capillary blood.

5) Starling forces in the peritubular capillary blood govern how much of this isosmotic fluid will be reabsorbed.

6) Fluid reabsorption is increased by increases in oncotic pressure of the peritubular capillary blood and decreased by decreases in oncotic pressure.

7) Increases in GFR and filtration fraction cause the protein concentration and oncotic pressure of peritubular capillary blood to increase. This increase, in turn, produces an increase in fluid reabsorption. Thus, there is matching of filtration and reabsorption, or glomerulotubular balance.

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187
Q

Effects of ECF volume on proximal tubular reabsorption

A

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

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

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188
Q

Renal regulation of K

A

o K+ is filtered, reabsorbed, and secreted by the nephron.

o K+ balance is achieved when urinary excretion of r exactly equals intake of K in the diet.

o K+ excretion can vary widely from 1% to 110% of the filtered load, depending on dietary K+ intake, aldosterone levels, and acid-base status.

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189
Q

Summary of K processes across renal neprhon

A

1) Glomerular capillaries -filtration occurs freely across the glomerular capillaries. Therefore, TF/P of K in Bowman space is 1.0.

2) Proximal tubule reabsorbs 67% of the filtered K+ along with Na+ and H20.

3) Thick ascending limb of the loop of Henle reabsorbs 20% of the filtered K+.
Reabsorption involves the Na+-K+-2cl- cotransporter in the luminal membrane of cells in the thick ascending limb.

4) Distal tubule and collecting duct either reabsorb or secrete K+, depending on dietary K+ intake.

o Reabsorption of K involves an H+ / K+ -ATPase in the luminal membrane of the intercalated A cells. Occurs only on a low-K+ diet (K+ depletion). Under these conditions, K+ excretion can be as low as 1% of the filtered load because the kidney conserves as much K+ as possible.

o Secretion of K+ occurs in the principal cells. Is variable and accounts for the wide range of urinary K+ excretion. Depends on factors such as dietary K+, aldosterone levels, acid-base status, and urine flow rate.
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190
Q

Causes of changes in K+ distal secretion

A
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191
Q

T/F Hyperaldosteronism causes hyperkalemia

A

FALSE - causes HYPOkalemia

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192
Q

What is the effect of loop and thiazide diuretics on K secretion?

A

o They increase K+ secretion.

o Loop and thiazide diuretics that increase flow rate through the late distal tubule and collecting ducts cause dilution of the luminal K+ concentration, increasing the driving force for K+ secretion.

o Loop and thiazide diuretics also increase Na+ delivery to the late distal tubule and collecting ducts, which leads to increased Na+ entry across the luminal membrane of principle cells, increased Na+ pumping out of the cells by the Na+-K+ pump, increased intracellular K+ concentration, and increased driving force for K+ secretion.

o Also, as a result of increased K+ secretion, these diuretics cause hypokalemia.

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193
Q

K+ sparing diuretics

A

o Decrease K+ secretion. If used alone, they cause hyperkalemia.

o Spironolactone is an antagonist of aldosterone; triamterene and amiloride act directly on the principal cells.

o The most important use of the K-sparing diuretics is in combination with thiazide or loop diuretics to offset (reduce) urinary K losses.

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194
Q

T/F - Excess anions (e.g., HC03-) in the lumen cause an increase in K+ secretion by increasing the negativity of the lumen and increasing the driving force for K+ secretion.

A

TRUE

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195
Q

Regulation of urea excretion

A

o Urea is reabsorbed and secreted in the nephron by diffusion, either simple or facilitated, depending on the segment of the nephron.

o Fifty percent of the filtered urea is reabsorbed in the proximal tubule by simple diffusion.

o Urea is secreted into the thin descending limb of the loop of Henle by simple diffusion (from the high concentration of urea in the medullary interstitial fluid).

o The distal tubule, cortical collecting ducts, and outer medullary collecting ducts are impermeable to urea; thus, no urea is reabsorbed by these segments.

o ADH stimulates a facilitated diffusion transporter for urea in the inner medullary collecting ducts. In the presence of ADH, urea reabsorption from inner medullary collecting ducts contributes to urea recycling in the inner medulla and to the addition of urea to the corticopapillary osmotic gradient.

o Urea excretion varies with urine flow rate. At high levels of water reabsorption (low urine flow rate), there is greater urea reabsorption and decreased urea excretion. At low levels of water reabsorption (high urine flow rate), there is less urea reabsorption and increased urea excretion.

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196
Q

Regulation of phosphate

A

o Eighty-five percent of the filtered phosphate is reabsorbed in the proximal tubule by Na+- phosphate cotransport. Because distal segments of the nephron do not reabsorb phosphate, 15% of the filtered load is excreted in urine.

o Parathyroid hormone (PTH) inhibits phosphate reabsorption in the early proximal tubule by activating adenylate cyclase, generating cAMP, and inhibiting Na+-phosphate cotransport. Therefore, PTH causes phosphaturia and increased urinary cAMP.

o Phosphate is a urinary buffer for H+; excretion of H2P04- is called titratable acid.

o Fibroblast growth factor (FGF23), which is secreted by bone, inhibits Na+-phosphate cotransport in the early proximal tubule.

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197
Q

Regulation of Ca2+

A

o 60% of the plasma Ca2+ is filtered across the glomerular capillaries.

o Together, the proximal tubule and thick ascending limb reabsorb more than 90% of the filtered Ca2+by passive processes that are coupled to Na+ reabsorption.

o Loop diuretics (e.g., furosemide) cause increased urinary Ca2+ excretion. Because Ca2+ reabsorption is driven by the lumen-positive potential difference in the loop of Henle, inhibiting the Na+-zCI–K+ cotransporter reabsorption with a loop diuretic inhibits the lumen-positive potential difference and thereby inhibits Ca2+reabsorption. If volume is replaced, loop diuretics can be used in the treatment of hypercalcemia.

o Together, the distal tubule and collecting duct reabsorb 8% of the filtered Ca2 + by an active process, based on hormonal signals -> PTH increases Ca2+reabsorption by activating adenylate cyclase in the distal tubule.

o Thiazide diuretics increase Ca2+ reabsorption in the early distal tubule and therefore decrease Ca2+excretion. For this reason, thiazides are used in the treatment of idiopathic hypercalciuria.

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198
Q

Regulation of Mg2+

A

o It is reabsorbed in the proximal tubule, thick ascending limb of the loop of Henle, and distal tubule.

o In the thick ascending limb, Mg2+ and Ca2+compete for reabsorption; therefore, hypercal- cemia causes an increase in Mg2+ excretion (by inhibiting Mg2+ reabsorption).

o Likewise, hypermagnesemia causes an increase in Ca2+ excretion (by inhibiting Ca2+ reabsorption).

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199
Q

What is a concentrated urine?

A

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

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200
Q

When do we produce a concentrated urine?

A

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

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201
Q

Explain what is the corticopapillary osmotic gradient

A

o Is the gradient of osmolarity from the cortex (300 mOsm/L) to the papilla (1200 mOsm/L) and is composed primarily of NaCl and urea.

o Is established by countercurrent multiplication in the loops of Henle and urea recycling in the inner medullary collecting ducts.

o Is maintained by countercurrent exchange in the vasa recta.

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202
Q

Corticopapillary osmotic gradient -> countercurrent multiplier in the LOH

A

o Depends on NaCI reabsorption in the thick ascending limb and countercurrent flow in the descending and ascending limbs of the loop of Henle.

o Is augmented by ADH, which stimulates NaCl reabsorption in the thick ascending limb. Therefore, the presence of ADH increases the size of the corticopapillary osmotic gradient.

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203
Q

Corticopapillary osmotic gradient -> urea recycling and vasa recta

A

o Urea recycling from the inner medullary collecting ducts into the medullary interstitial fluid also is augmented byADH (by stimulating the UT1 transporter).

o Vasa recta are the capillaries that supply the loop of Henle. They maintain the corti- copapillary gradient by serving as osmotic exchangers. Vasa recta blood equilibrates osmotically with the interstitial fluid of the medulla and papilla.

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204
Q

Osmolarity of proximal tubule

A

o The osmolarityof the glomerular filtrate is identical to that of plasma (300 mOsm/L).

o Two-thirds of the filtered H20 is reabsorbed isosmotically (with Na+, a-, HC03-, glucose, amino acids, and so forth) in the proximal tubule.

o TF/Posm = 1.0 throughout the proximal tubule because H20 is reabsorbed isosmotically with solute.

205
Q

Osmolarity of thick ascending limb of LOH

A

o It is also called the diluting segment.

o Reabsorbs NaCl by the Na+/K+/2CI- cotransporter

o Is impermeable to H20. Therefore, H20 is not reabsorbed with NaCl, and the tubular fluid becomes dilute.

o The fluid that leaves the thick ascending limb has an osmolarity of 100 mOsm/L and TF/Posm <1.0 as a result of the dilution process.

206
Q

Osmolarity of early DT

A

o It is called the cortical diluting segment.

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

207
Q

Osmolarity of late DT

A

o ADH increases the H2O permeability of the principal cells of the distal tubule.

o H2O is reabsorbed from the tubule until the osmolarity of distal tubular fluid equals that of the surrounding interstitial fluid in the renal cortex (300mOsm/L)

o TF/Posm = 1.0 at the end of the distal tubule because osmotic equilibration occurs in the presence of ADH.

208
Q

Osmolarity of collecting ducts

A

o As in the late DT, ADH increases H2O permeability of the principal cells of the collecting ducts.

o As tubular fluid flows through the collecting ducts, it passes through the corticopapillary gradient (regions of increasingly higher osmolarity), which was previously established by countercurrent multiplication and urea recycling.

o H20 is reabsorbed from the collecting ducts until the osmolarity of tubular fluid equals that of the surrounding interstitial fluid.

o The osmolarity of the final urine equals that at the bend of the loop of Henle and the tip of the papilla (1200 mOsm/L).

o TF/Posm >1.0 because osmotic equilibration occurs with the corticopapillary gradient in the presence of ADH.

209
Q

When do we produce diluted urine?

A

o Is called hyposmotic urine, in which urine osmolarity < blood osmolarity.

o Is produced when circulating levels of ADH are low (e.g., water intake, central diabetes insipidus) or when ADH is ineffective (nephrogenic DI).

210
Q

Summary of osmolarities on nephrons when producing diluted urine

A

1) Corticopapillary osmotic gradient -> no ADH. Is smaller than in the presence of ADH because ADH stimulates both countercurrent multiplication and urea recycling.

2) Proximal tubule–no ADH. As in the presence of ADH, two-thirds of the filtered water is reabsorbed isosmotically. TF/Posm =1.0 throughout the proximal tubule.

3) Thick ascending limb of the LOH - no ADH. As in the presence of ADH, NaCl is reabsorbed without water, and the tubular fluid becomes dilute (although not quite as dilute as in the presence of ADH). TF/Posm< 1.0.

4) Early DT -> no ADH. As in the presence of ADH, NaCl is reabsorbed without H20 and the tubular fluid is further diluted. TF/Posm < 1.0.

5) Late distal tubule and collecting ducts -> no ADH. In the absence ofADH, the cells of the late distal tubule and collecting ducts are impermeable to H20. Thus, even though the tubular fluid flows through the corticopapillary osmotic gradient, osmotic equilibration does not occur.

6) The osmolarity of the final urine will be dilute with an osmolarity as low as 50m0sm/L.
TF/Posm< 1.0.

211
Q

What is the free-water clearance?

A

o It is used to estimate the ability to concentrate or dilute the urine.

o Free water, or solute-free water, is produced in the diluting segments of the kidney {i.e., thick ascending limb and early distal tubule), where NaCl is reabsorbed and free water is left behind in the tubular fluid.

o In the absence of ADH, this solute-free water is excreted and CH20 is positive.

o In the presence of ADH, this solute-free water is not excreted but is reabsorbed by the late distal tubule and collecting ducts and CH2O is negative.

212
Q

How do we calculate free-water clearance?

A
213
Q

Example of free-water clearance calculation - if the urine flow rate is 10 mL/min, urine osmolarity is 100 mOsm/L, and plasma osmolarity is 300 mOsm/L, what is the free-water clearance?

A
214
Q

T/F - Urine that is isosmotic to plasma (isosthenuric), CH2O is zero

A

TRUE

215
Q

T/F Urine that is hyposmotic to plasma, CH2O is negative

A

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

216
Q

ADH pathology - changes in serum osmolarity (serum Na) and urine osmolarity

A
217
Q

Summary of hormones that act on the kidney

A
218
Q

What types of acids are produced in the body?

A

Two: volatile and nonvolatile acids

219
Q

What is a volatile acid?

A

o C02, produced from the aerobic metabolism of cells.

o C02 combines with H20 to form the weak acid H2C03, which dissociates into H+ and HC03- by the following reactions:

C02 + H20 <–> H2C03 <–> H+ + HCO3-

o Carbonic anhydrase, which is present in most cells, catalyzes the reversible reaction between C02 and H20.

220
Q

What is a nonvolatile acid?

A

o They are also called fixed acids

o Include sulfuric acid (a product of protein catabolism) and phosphoric acid (a product of phospholipid catabolism).

o They are normally produced at a rate of 40 to 60mmoles/d.

o Other fixed acids that may be overproduced in disease include ketoacids and lactic acid., or may be ingested including salicylic acid, formic acid (methanol poisoning), and oxalic and glycolic acids (ethylene glycol poisoning).

221
Q

What is a buffer

A

o Substance that can prevent a change in pH when H+ ions are added or removed to/from a solution.

o Normally it consist of a weak acid and its conjugate base, or a weak base and its conjugated acid.

o Are most effective within 1.0pH unit of the pK of the buffer.

222
Q

Where can buffers be found?

A

Extracellular buffers and intracellular buffers

223
Q

Extracellular buffers

A

o The major extracellular buffer is HCO3- which is produced from C02 and H20. The pK of the C02/HC03- buffer pair is6.1.

o Phosphate is a minor extracellular buffer. The pK of the H2P04- / HPO4-2 buffer pair is 6.8. Phosphate is most important as a urinary buffer; excretion of H+ as H2P04- is called titratable acid.

224
Q

Intracellular buffers

A

o Organic phosphates (e.g., AMP, ADP, ATP, 2,3-DPG)

o Proteins
* Imidazole and alpha-amino groups on proteins have pKs that are within the physiologic pH range.
* Hemoglobin is a major intracellular buffer.
* In a physiologic pH range, deoxyhemoglobin is a better buffer than oxyhemoglobin.

225
Q

What are the 2 most widely accepted schemes in human medicine for acute kidney injury?

A
  • RIFLE -> Risk Injury Failure End Stage Kidney Disease
  • AKIN -> Acute Kidney Injury Network
226
Q

In which patients is the estimation of GFR reliable?

A

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

227
Q

What is KDIGO

A

Kidney Disease Improving Global Outcomes initiative

228
Q

According to KDIGO, what are the 3 main ways to recognize AKI?

A

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

229
Q

What are the issues with creatinine as a marker?

A

o It is a functional marker, not a biomarker

o Patients with either pre-renal or intrinsic AKI, they will have larges decreases in GFR but creatinine will change very little -> can lose more than 50-60% of the functional renal capacity and still be non azotemic -> prevents early recognition if we only rely on creatinine.

o Once the patient becomes azotemic, then there will be probably very little changes in GFR and creatinine changes are larger (can be very large and GFR not change that much on late phases of AKI)

230
Q

What is the ideal biomarker?

A

o Easy and simple to measure

o Consistent repetitive measurement

o Threshold values well documented and validated

o Correlate with the presence of illness and its severity

o Reasonable cost

o Measurable in biological fluids

231
Q

T/F - SDMA is a helpful marker that allows clinicians to differentiate between AKI and CKD

A

FALSE - it has been looked at in AKI and CKD patients.

o It is based on function and not ongoing damage -> both AKI and CKD have decreased renal function.

o As seen in the graph, no difference between levels of SDMA in patients with AKI compared to CKD.

o Then SDMA does not seem very useful in the critical care setting -> first, in an azotemic patient, SDMA will be elevated but not give an answer on the pathology or etiology. Second, studies show that patients with AKI and azotemic, SDMA remains normal.

o It is important in stable patients when trying to recognize early CKD - prep, geriatric.

232
Q

Urinary GGT

A

o Based on function, not on tubular cell damage.

o Useful, but like many other functional markers (like SDMA), once patient is azotemic then they are not useful.

o In nonazotemic or in hospital AKI it has not been validated.

233
Q

Plasma NGAL in dogs with AKI

A

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

234
Q

Urine NGAL in dogs with gentamicin- induced nephrotoxicity

A

o Urine NGAL to creatinine ration (UNCR) increases around day 11 or so and peaks around day 17-18

o Plasma creatinine has a delay of 4-5 days in becoming elevated, and the peak is also delayed compared to NGAL.

o Also important during recovery - identifying patients that are responding to therapy or not

235
Q

Damage biomarkers vs functional biomarkers

A
236
Q

Urinary biomarkers in hospital-acquired AKI

A

o Urinary microscopy is important!!! -> presence of epithelial cells, casts

o Other biomarkers might not be available and when we have a patient with a urinary catheter, we do not have to forget to assess urine microscopy as it can be very valuable.

237
Q

Etiology of AKI

A
238
Q

Based upon the results of a study by J. Martinez et al. published in JVECC 2020, what perfusion parameters were associated with the development of AKI in dogs with pit viper envenomation?

A

Tachycardia, hypotension and shock index

Also, number of vials of antivenom, vials of antivenom/kg and receiving pRBCs.

239
Q

What happens when a patient is in shock and reaches the critical DO2?

A

Blood flow redistribution
Capillary recruitment
Ischemia: GI, kidneys, lungs

Dysoxia - abnormal tissue oxygen metabolism
* Lactate production
* Metabolic acidosis
* Na/K ATPase pump dysfunction
* Cytotoxic edema
* Increased Ca2+
* Cell death

240
Q

Causes of renal tubular injury

A
241
Q

In relation to the pathophysiology of AKI secondary to ethylene glycol toxicosis, which enzyme is the rate limiting factor in the metabolism of ethylene glycol?

A

o Alcohol dehydrogenase

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

242
Q

Coral snake bite -> phospholipase A leads to?

A

RBCs destruction -> hemolysis -> hemoglobinuria

243
Q

Renal etiology - interstitial nephritis

A

o One of the most common causes of AKI

o Probably community acquired AKI - patients will come with azotemia already.

o Some causes: pyelonephritis, leptospirosis, granulomatous disease (systemic aspergillosis), neoplasia (lymphoma)

244
Q

Does a negative urine culture rule out pyelonephritis?

A

No

245
Q

Based upon the results of a study by Lizer et al.published in JVIM in 2018, which serological test demonstrated the best performance in detecting Leptospirosis early in the course of the infection?

A

o Witness leptospirosis test (remember PCR is not a serologic test!!)

o Based in IgM levels that raise early in acute phase compared to IgG levels measured by common micro agglutination tests.

o Superior in recognizing clinical disease in the first 14 days of the infection

o After those 14 days, IgM tend to decrease and IgG starts to increase.

246
Q

Causes of post-renal AKI

A

o Obstructive diseases: urolithiasis, neoplasia, prostatic disease, FLUTD

o Uroabdomen

o Vital early intervention, surgical disease.

247
Q

Based upon the results of a study performed by Kulendra et al. published in JSAP 2020, what was the approximate median survival time in cats managed with SUB placement based on IRIS AKI stage?

A

IRIS stage I-III -> more than 900 days
IRIS stage IV-V -> less than 600 days

o Early treatment has a great MST!

248
Q

Other causes of AKI in CI patients

A

o Nephrotoxic medications
o Uncorrected cardiovascular shock
o Fluid overload

249
Q
A
250
Q

Why Cl rich solutions can be detrimental for kidney function?

A

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

251
Q
A
252
Q

Composition of isotonic (replacement fluids) - table

A
253
Q
A
254
Q

Based upon results of a study by Schmid et al. published in JVECC 2019, which postmortem renal pathology was associated with the use of hetastarch in critically-ill dogs?

A

Renal tubular vacuolization

255
Q

T/F SQ edema develop before visceral edema

A

FALSE - it develops after visceral edema

256
Q

How can we assess renal recovery?

A
257
Q

Summary of findings from “Glomerular Filtration Rate, Urine Production, and Fractional Clearance of Electrolytes in Acute Kidney Injury in Dogs and Their Association with Survival” JVIM 2015

A
258
Q

Summary of “Controversies in the management of feline urethral obstruction” JVECC 2015

A
259
Q

Summary of “Acute Azotemia as a Predictor of Mortality in Dogs and Cats” JVIM 2012

A

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

260
Q

AKIN criteria

A
261
Q

RIFLE criteria

A
262
Q

Summary of “Acute kidney injury in severe sepsis: Pathophysiology, diagnosis, and treatment recommendations” JVECC 2015

A
263
Q

Summary of “Effects of Hydroxyethyl Starch 130/0.4 on Serum Creatinine Concentration and Development of Acute Kidney Injury in Nonazotemic Cats” JVIM 2017

A
264
Q

Summary of “Associations among Albuminuria, C-Reactive Protein Concentrations, Survival Predictor Index Scores, and Survival in 78 Critically Ill Dogs” JVIM 2011

A
265
Q

What are the goals of fluid resuscitation in AKI?

A
266
Q

ISCAID guidelines - summary of recommendations for diagnosis of uncomplicated UTI’s

A

o Simple uncomplicated UTI is a sporadic bacterial infection of the bladder in an otherwise healthy individual with normal urinary tract anatomy and function.

o Clinical signs are nonspecific and should not be used alone for diagnosis of UTI.

o Aerobic bacterial culture and susceptibility testing should be performed in all cases, to confirm the presence of infection, identify the presence of resistant bacteria, to help differentiate reinfection from relapse, and to provide the clinician with guidance.

o Cystocentesis should be used for sample collection. Catheterized samples can be evaluated for culture but cystocentesis samples are preferred. Free-catch (midstream voiding or manual expression) samples should not be used.

o It is imperative that a quantitative culture be performed.

o Urine samples for culture and susceptibility testing should be refrigerated immediately after collection and submitted to the laboratory asap. Results of samples that take 24 hours or more to reach the laboratory should be interpreted with caution because of the potential for both false positive and false negative results

o For samples collected by cystocentesis, any level of bacterial growth may be significant, although samples from a UTI typically contain ≥10^3 colony forming units (CFU)/mL

o For samples collected via catheter, bacterial counts ≥10^4 CFU/mL in males and ≥10^5 in females are typically considered significant.

267
Q

ISCAID guidelines - summary of recommendations for treatment and monitoring of uncomplicated UTI’s

A

o Antimicrobial therapy is indicated in most cases while awaiting culture and susceptibility results to relieve patient discomfort.

o In most situations, initial therapy should consist of amoxicillin (11– 15 mg/kg PO q8h) or trimethoprim-sulfonamide (15 mg/kg PO q12h).

o Amoxicillin/clavulanic acid (12.5–25mg/kg PO q8h) is an acceptable option but is not recommended initially because of the lack of evidence regarding the need for clavulanic acid and the desire to use the narrowest spectrum that is possible while maintaining optimal efficacy.

o If culture and susceptibility testing indicates the presence of an isolate that is resistant in vitro but there has been apparent clinical response, maintaining the current treatment is acceptable provided a follow-up urinalysis, including culture, is performed after treatment has been completed to ensure resolution of infection.

o If culture and susceptibility data indicate that the isolate is not susceptible to the chosen antimicrobial and there is a lack of clinical response, then therapy with the original drug should be discontinued and treatment with an alter- native drug begun.

o Adequate evidence regarding duration of treatment is lacking, precluding the ability to make a specific recom- mendation for treatment duration. Typically, uncomplicated UTIs are treated for 7–14 days. Shorter treatment time (≤7 days) may be effective.

o There is no indication for measures beyond monitoring of clinical signs.

268
Q

ISCAID guidelines - complicated UTI’s

A

o A complicated UTI is an infection that occurs in the presence of an anatomic or functional abnormality or a comorbidity that predisposes the patient to persistent infection, recurrent infection, or treatment failure.

o In humans, the concurrent presence of prostatitis, urinary calculi, a neurogenic bladder, pregnancy, diabetes mellitus, or immunocompromising disorders also defines a complicated UTI. it is reasonable to apply this to companion animals.

o Recurrent UTIs, as defined by the presence of 3 or more episodes of UTI during a 12-month period also indicate complicated infection.

o Reinfection is recurrence of a UTI within 6 months of cessation of previous, apparently successful treatment and isolation of a different microorganism.

o Relapse is recurrence of a UTI within 6 months of cessation of previous, apparently successful treatment and isolation of an indistinguishable organism from the one that was present previously, which is presumably because of failure to completely eliminate the pathogen.

o A refractory infection is similar to a relapse except that it is characterized by persistently positive results using culture during treatment (despite in vitro susceptibility to the antimicrobial), with no period of eliminated of bacteriuria during or after treatment.

269
Q

ISCAID guidelines - summary of recommendations for diagnosis of complicated UTI’s

A

o General principles of diagnosis for simple uncomplicated UTI, apply for complicated UTIs.

o A diagnosis of recurrent UTI should never be based on clinical signs or urine sediment examination alone. Bacterial culture and susceptibility testing should be performed in all instances to confirm recurrent UTI.

o Determine any underlying factors that could be associated with recurrence or relapse. A CBC/chem, UA, imaging and, if deemed appropriate, endocrine testing should be performed. A complete PE, including rectal palpation and examination of the vulva is required.

o If cystotomy is being performed, culture of a bladder wall biopsy as well as any uroliths that might be present is recommended.

270
Q

ISCAID guidelines - summary of recommendations for treatment of complicated UTI’s - I

A

o If the clinical condition of the patient permits, consideration should be given to waiting for culture results before starting therapy.

o If treatment must be initiated immediately, a drug should be selected from those recommended for initial treatment of simple uncomplicated UTI.

o Where possible, the drug class used should be different from that used to treat the prior UTI(s) (i.e., if amoxicillin was used initially, start treatment with trimethoprim-sulfadiazine).

o After treatment has been initiated, continued treatment should be based on the results of culture and susceptibility testing. Preference should be given to drugs that are excreted in urine predominantly in an active form.

o If more than one bacterial species is identified on initial culture, the relevance of the each organism should be considered, based on the bacterial counts and the pathogenicity of the organisms.

o When present in a mixed infection, anecdotal evidence suggests that infection by Enterococcus spp. will often resolve when the other organism is successfully treated.

o Ideally, antimicrobial therapy should be directed against both organisms. In some instances, an antimicrobial effective against both organisms will not be available. Combination therapy that would be potentially effective against both organisms should be considered

271
Q

ISCAID guidelines - summary of recommendations for treatment of complicated UTI’s - II

A

o There is no supporting evidence for administration of other drugs (e.g., clarithromycin) for the purpose of breaking down bacterial biofilm.

o There is no supporting evidence that direct instillation of antimicrobials, antiseptics, or DMSO directly into the bladder via a urinary catheter is effective for treatment of recurrent UTIs. These compounds are quickly flushed out of the bladder when the animal urinates and may be locally irritating.

o Any underlying causes should be managed appropriately, whenever possible.

o Evidence supporting the duration of therapy for complicated UTI does not exist. Typically, 4 weeks of treatment has been recommended.

272
Q

ISCAID guidelines - summary of recommendations for monitoring of complicated UTI’s - III

A

o Urine culture should be considered 5–7 days after initiation of therapy, particularly in patients with a history of relapsing or refractory infection, or those considered at high risk for ascending or systemic infection.

o Any bacterial growth during treatment indicates potential treatment failure and should prompt immediate reevaluation.

o Urine culture is recommended 7 days after cessation of therapy in all cases.

o Although there is some evidence for a benefit of nutritional supplements (e.g., cranberry juice extract) for this indication in humans, the evidence is not strong and some studies have shown no effect in dogs and cats.

273
Q

ISCAID guidelines - subclinical bacteriuria

A

o Subclinical bacteriuria is the presence of bacteria in the urine as determined by positive bacterial culture, in the absence of clinical and cytological evidence of UTI.

o Treatment may not be necessary in animals that have no clinical signs of UTI and no evidence of UTI based on examination of urine sediment.

o Treatment may be considered if there is concern that there is a particularly high risk of ascending or systemic infection (e.g., immunocompromised patients, patients with underlying renal disease).

o The presence of multidrug-resistant bacterium does not represent, by itself, an indication for treatment.

o Anecdotal information suggests that multidrug-resistant organisms will sometimes be replaced with susceptible organisms if treatment is withheld -> then treatment with routine antimicrobials may be more practical if decolonization is desired or if clinical disease develops.

274
Q

ISCAID guidelines - urinary catheters + no UTI signs

A

o UTI and subclinical bacterial colonization of the bladder are commonly identified in dogs with indwelling urinary catheters.

o Animals with u-caths and no clinical sx of infection -> culture for diagnosis of the presence of bacteria in urine is not recommended in the absence of clinical signs consistent with an active infection.

o It is not necessary to treat catheterized animals with bacteriuria in the absence of clinical or cytological evidence supporting the presence of an infection.

o Prophylactic antimicrobial therapy for prevention of UTI in catheterized animals is never indicated.

o When u-cath is being removed -> no evidence supporting the need to culture the catheter tip at time of catheter removal since catheter tip culture results are not predictive of development of catheter-associated UTI.

o No evidence supporting routine culture of urine after catheter removal. However, culture of the urine (ideally collected by cystocentesis after catheter removal) may be reasonable in patients in which the risk and implications of UTI are high (e.g., recently obstructed male cat with at high risk for reobstruction).

o Clinical monitoring and cytological examination to detect a potential UTI are preferred to urine culture in a patient with no signs of UTI.

o There is no indication for routine (prophylactic) antimicrobial treatment following urinary catheter removal in an animal with no clinical or cytological evidence of active UTI

275
Q

ISCAID guidelines - urinary catheters + UTI signs

A

o Suspect UTI if u-cath + clinical signs.

o Infection should be suspected in all cases of fever of unknown origin or bacteremia with an unknown focus. Infection should also be suspected when there are gross or cytological (i.e., hematuria, pyuria) abnormalities.

o Urine culture should always be performed if infection is suspected.

o If a catheter must remain in place and signs of UTI are present, the catheter should be replaced and a urine sample collected through the new catheter for culture. Several mL of urine should be withdrawn to clear the catheter and discarded prior to obtaining the sample for culture.

o When possible, catheters should be removed and urine sampled by cystocentesis after an appropriate period of time has passed for the bladder to fill with urine.

o Urine culture should never be performed from the collection bag.

o Treatment is more likely to be successful if the catheter can be removed.

276
Q

ISCAID guidelines - pyelonephritis treatment

A

o Treatment should be initiated immediately, while awaiting culture and susceptibility results.

o Initial treatment should involve antimicrobial drugs known to have local or regional efficacy against Gram-negative Enterobacteriaceae, based on the predominance of those organisms in pyelonephritis.

o If regional data are supportive, treatment with a fluoroquinolone excreted in urine in the active form is a reasonable first choice.

o If ascending infection is suspected, urine culture results obtained for diagnosis of lower UTI might be the basis of initial therapy.

o If the upper UTI results from hematogenous spread, initial therapy should be based on cultures of blood or the infected site, whenever available.

o Treatment of 4–6 weeks is often recommended. A shorter duration might be effective; however there is currently inadequate evidence to provide objective recommendations.

o UA and culture should be performed 1 week from the start of treatment because of potential severity of disease and long treatment duration. If the same organism is isolated, one should consider adding an antimicrobial to which the organism is susceptible in vitro, if possible.

o Culture is recommended 1 week after cessation of therapy to ensure elimination of infection.

277
Q

ISCAID guidelines - MDR infections

A

o Multidrug-resistant pathogens, including various Enterobacteriaceae, staphylococci, and enterococci, are becoming increasingly problematic.

The use of drugs such as vancomycin, carbapenems, and linezolid is not justified unless the following criteria are met:

1) Infection must be documented based on clinical, culture, and cytological abnormalities. The use of these drugs for the treatment of subclinical infection is not supported.

2) Resistance to all other reasonable options and susceptibility to the chosen antimicrobial must be documented.

3) The infection must be potentially treatable. The use of critical drugs in situations where there is little realistic chance of elimination of infection (e.g., failure to remove the underlying cause) is not supported.

4) Consultation with someone with expertise in infectious diseases and antimicrobial therapy must be obtained to determine whether there are any other viable options and whether treatment is reasonable.

278
Q

Extracorporeal therapies include

A

o Renal replacement
o Therapeutic plasma exchange
o Hemoperfusion

279
Q

Name methods of clearance of the ECT

A

Diffusion
Convection
Ultrafiltration
Adsorption

  • Metabolism of the substance -> provided by the patient.
280
Q

What is diffusion?

A

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

281
Q

T/F - The lower the concentration gradient between the 2 sides of a semipermeable membrane, the faster the rate of diffusion

A

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

282
Q

What are the 2 solutions in dialytic therapies?

A

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

283
Q

T/F - by constant replenishment of the dialysate, a large concentration gradient is maintained -> equilibrium is never reached so diffusive clearance continues

A

TRUE

284
Q

Rates of dialysate flow in intermittent hemodialysis?

A

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

285
Q

Describe peritoneal dialysis

A

o Involves installation of a discrete volume of dialysate that is periodically removed and replaced with fresh dialysate.

o During the dwell time, diffusion occurs -> short dwell times (1-2h) used in AKI do not allow complete equilibrium - frequent exchanges increase the overall uremic toxin removal.

286
Q

In oliguric renal failure patients they might need fluid to be removed, and diuretics can become ineffective. What would be the best method to removing the fluid?

A

Ultrafiltration

287
Q

What principle uses ultrafiltration?

A

o It involves a hydrostatic pressure gradient to cause water movement.

o By creating negative pressure on the side opposite to the blood compartment, water is “pulled” out of the blood.

288
Q

Explain the coefficient of ultrafiltration (KUF)

A

o Number of mL of fluid transferred across the membrane per hour when 1mmHg of transmembrane pressure is applied.

o With a higher KUF, less of a pressure gradient is needed to remove fluid.

289
Q

What is convective clearance?

A

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

290
Q

T/F - Compounds with a MW 500-5000Da are more efficiently cleared with convection compared to diffusion

A

TRUE

291
Q

T/F - Diffusion is very efficient for small molecules, like urea, creatinine or sodium

A

TRUE

292
Q

T/F Hemofiltration indicates using convective clearance for uremic toxin removal

A

TRUE

293
Q

T/F - Hemodialysis indicates using diffusive clearance

A

TRUE

294
Q

What is RRT?

A

RRT = Renal Replacement Therapy

Extracorporeal form of therapy that replaces the non-endocrine function of the kidneys

• Excretion of uremic waste products
• Restoration of acid-base balance
• Restoration of body water balance

295
Q

T/F Therapeutic plasma exchange is a convective therapy

A

TRUE

296
Q

Explain TPE

A

o The semipermeable membrane has larger pores that allow plasma proteins (immunoglobulins) to be removed, leaving behind the cellular component.

o Since plasma is being removed, part of the replacement fluid is typically FFP, although part may be other colloids or crystalloid fluids.

297
Q

Absorption

A

o Certain substances, like cytokines, will bind to the dialyzer membrane and therefore, they can be removed from the circulation.

o The adsorptive capacity of the dialysis membrane is limited -> ineffective method of removal.

o Charcoal and other hemoperfusion techniques are better suited for significant adsorption.

298
Q

When are charcoal or carbon cartridges helpful?

A

o In removing substances that have significant protein binding.

o The unbound portion of the substance will bind to the carbon, and a small amount of the substance will dissociate from protein, making it available to bind to the carbon.

o Carbon cartridges become saturated with the substance within several hours -> the exact time will depend on the concentration of the substance and the amount of charcoal.

299
Q

Define extraction ratio

A

o The % of a substance removed in a single pass through the dialyzer or divide.

o Measured by sampling the blood entering and the blood exiting the device

o Formula => (Con in - Con ou) / Con in

Con = concentration

300
Q

Clearance of a dialyzer

A

o Volume of blood completely cleared of a certain solute during a single pass through the device (same concept as renal clearance).

o Clearance = Qb x ((Con in - Con out)/Con in)
Qb => flow rate

o Units: mL/min

301
Q

T/F - Increasing the surface area for diffusion increases the clearance, but at the cost of requiring a larger volume of blood to fill the dialyzer

A

TRUE

302
Q

T/F - In IHD the dialysate flor rate (around 500mL/min) is much faster than the blood flow rate (10-300mL/min)

A

TRUE

303
Q

Explain why the dialysate flow rate is higher than the blood flow rate

A

o At slower blood flow rates, the blood may be completely cleared of small solutes such as urea in one pass through the dialyzer (100% extraction), in which case the blood flow rate approximates clearance.

o At fast blood flow rates relative to the dialysate rate, the blood may not reach equilibrium and the extraction rate will be lower.

304
Q

Equation that determines convective clearance

A

Clearance = Jf x Cs x S

Jf = amount of ultrafiltration

Cs = concentration of solute

S = sieving coeficient.

305
Q

T/F - A sieving coeficient of 1 means the soulte does not get filtered at all

A

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

306
Q

What is the most commonly used measure of clearance in veterinary mehodialysis?

A

Urea reduction ratio (URR)

307
Q

Urea reduction ratio (URR)

A

URR = (BUNpre - BUNpost) / BUNpre

308
Q

If a substance is >95% protein bound, what may be the most effective treatment to remove it?

A

TPE.

309
Q

What is typically TPE used for?

A

To remove immunoglobulins.

310
Q

If by TPE we remove a volume of plasma equal to the patient’s plasma volume, which % of immunoglobulins are we removing?

A

o 63%

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

311
Q

Normal plasma osmolality of dog and cat

A

Dog - 290-310mOsm/kg

Cat - 308-335mOsmo/kg

312
Q

What is prioritized, maintenance of effective circulating volume or plasma osmolality?

A

Maintenance of effective circulating volume

313
Q

What happens when V2 receptors in the renal collecting duct are activated?

A

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

314
Q

How do most diuretics work?

A

o Increase urine production by altering solute reabsorption throughout the nephron.

o Water movement is passive -> water will follow the solutes -> increased tubular water content, increased urine volume and decreased ECF volume.

315
Q

Factors that affect diuretic potency

A
  • Dose administered.
  • The effect of the site of action
  • The ability of more distal segments to alter the filtrate
316
Q

T/F A diuretic that prevents Na reabsorption in the LOH will induce more natriuresis that one that acts proximally

A

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

317
Q

How do diuretics reach their site of action?

A

By filtration or secretion, except spironolactone.

318
Q

Carbonic anhydrase inhibitors MOA

A

o Will block the enzyme CA, decreasing the secretion of H+, increasing Na and HCO3- losses.

o Acetozolamide

o Limited effect due to increased distal reabsorption - not used to treat edematous conditions.

o Frequently used to decrease aqueous humor production in glaucoma patients.

319
Q

Why are sodium dependent glucose con transporters (SGLT) significant?

A

o Found within the PT and allow for the reabsorption across the apical membrane of 1 or 2 Na for each glucose.

o SGLT2 are responsible for 80-90% of the glucose reabsorption that occurs in the PT.

o In human medicine, SGLT2 inhibitors -> initially used as anti-diabetic drugs to prevent glucose reabsorption. They also induced transient natriuresis and osmotic diuresis.

o They have been shown to improve outcome in heart failure patients, regardless of diabetic status.

320
Q

SGLT2 inhibitors in veterinary medicine

A

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

o Examples: bexagliflozin, empagliflozin

321
Q

Site of action and MOA of loop diuretics

A

o NKCC cotransporter in the ascending LOH and macula densa

o Compete with chloride for its biding site on the carrier.

o When bound by a loop diuretic, the NKCC contransporter is inactive -> urinary loss of Na, K, Cl, Ca, Mg and Ph.

o Blockade of the MD carrier may impar normal tubuloglomerular feedback.

o Furosemide -> thought to have additional benefits: protection agains ischemic injury, vasodilatory effects and bronchial antispasmodic properties.

322
Q

Furosemide metabolism

A

o 90-95% protein bound and a weak organic acid -> minimally filtered at the glomerulus.

o Secreted via organic acid transporters (OAT) in the proximal tubule.

o Only unbound furosemide is available to bind NKCC carrier.

o Due to variations in bioavailability -> oral dose up to 5 times higher than IV dose to achieve similar diuresis.

o Patients with decreased GFR, kidney dysfunction or hypoalbuminemia -> higher dose might be necessary to reach therapeutic levels due to diminished drug excretion.

323
Q

T/F - Water reabsorption in the PT and LOH occurs via paracellular movement down it concentration gradient

A

TRUE

324
Q

Mannitol MOA

A

o Osmotic diuretic

o Non-reabsorbable polysaccharide

o After IV injection -> increase in intravascular osmolality -> water will move from intracellular space to intravascular space.

o Freely filtered in the glomerulus and prevents reabsorption of water in the PT and LOH.

o In patients with increased ICP -> thought to reduce pressure by different mechanisms:
* Decreased intracellular water content
* Rheologic properties
* Acts as free radical scavenger.

325
Q

Effects of mannitol in AKI patients?

A

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

326
Q

Which is the site of action of the thiazide diuretics?

A

o Na/Cl cotransporter in the distal tubule

o These cotransporters are responsible for 3-8% of Na reabsorption -> less potent than other diuretics.

o Secreted via organic acid transporters in the proximal tubule and compete for the chloride binding site on the cotransporter.

o Promote Na and Cl loss

o In contrast to loop diuretics, they result in Ca retention.

o More frequently used in a sequential nephron blockade strategy than as only med.

o May decrease urine output in patient with diabetes inspidus -> induce volume depletion -> promote proximal tubular Na reabsorption.

327
Q

Aldosterone antagonists MOA

A

o Release of aldosterone results in increased expression of Na channels on the apical membrane and Na/K ATPase channels on the basolateral membrane of the principal cells, to increase Na reabsorption.

o Aldosterone antagonists will competitively antagonize aldosterone receptor in the late distal tubule and collecting duct principal cells, decreasing Na reabsorption.

o Can be used in combination with other diuretic drugs or can be the only therapy for hyperaldosteronism.

o Associated with minimal potassium wasting and may reduce myocardial remodeling.

328
Q

What are aquatics?

A

o New class of drugs that directly antagonize V2 receptors.

o Promote excretion of free water by preventing the insertion of aquaporins in the luminal membrane of principal cells.

o In people used in hyponatremic edematous states like CHF or cirrhosis.

o Only one case report in vetted in a dog with SIADH.

329
Q

Summary of common used diuretics - example, nephron segment and site of action (table)

A
330
Q

What type of fluid loss is caused by adrenocortical insufficiency?

A

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

331
Q

If the plasma [Na+] is 140 mEq/L, the urine [Na+] is 700 mEq/L, and the urine flow rate is 1 mL/min, what is the clearance of Na+?

A

5mL/min

332
Q

T/F Angiotensin-converting enzyme (ACE) inhibitors dilate efferent arterioles and produce a decrease in GFR; these drugs reduce hyperfiltration

A

TRUE

333
Q

Vasodilation of renal arterioles, which leads to an increase in RBF, is produced by

A

Prostaglandins
Bradykinin
Nitric oxide
Dopamine.

334
Q

What’s the effect of ANP in RBF and GFR?

A

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

335
Q

RBF remains constant over the range of arterial pressures from ________mm Hg (autoregulation).

A

80 to 180mmHg

336
Q

What are the two mechanism of renal autoregulation

A

o Myogenic mechanism, in which the renal afferent arterioles contract in response to stretch. Thus, increased renal arterial pressure stretches the arterioles, which contract and increase resistance to maintain constant blood flow.

o Tubuloglomerular feedback, in which increased renal arterial pressure leads to increased delivery of fluid to the macula densa. The macula densa senses the increased load and causes constriction of the nearby afferent arteriole, increasing resistance to maintain constant blood flow.

337
Q

Inulin is infused in a patient to achieve a steady-state plasma concentration of 1 mg/mL. A urine sample collected during 1 hour has a volume of 60 mL and an inulin concentration of 120 mg/mL. What is the patient’s GFR?

A

120mL/min

338
Q

Why BUN increases more than creatinine in pre-renal azotemia?

A

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

339
Q

How does the filtration fraction affect the reabsorption in the proximal tubule?

A

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

Decreases in the filtration fraction produce decreases in the protein concentration of peritubular capillary blood and decreased reabsorption in the proximal tubule.

340
Q

What are the components (layers) of the glomerular filtration barrier?

A

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

341
Q

At the afferent arteriolar end of a glomerular capillary, PGC is 45 mm Hg, PBs is 10 mm Hg, and 1tGC is 27 mm Hg. What are the value and direction of the net ultrafiltration pressure?

A

8 mm Hg (favoring filtration)

342
Q

Describe how glucose is reabsorbed in the kidneys?

A

Na+-glucose cotransport in the early proximal tubule reabsorbs glucose from tubular fluid into the blood. There are a limited number of Na+ -glucose transporters.

At plasma glucose concentrations less than ~250 mg/ dL, all of the filtered glucose can be reabsorbed because plenty of carriers are available; in this range, the line for reabsorption is the same as that for filtration.

343
Q

T/F Threshold is defined as the plasma concentration at which glucose first appears in the urine. It is approximately 250 mg/dL

A

TRUE

344
Q

The reabsorptive rate at which the Na/Glu carriers are saturated in the proximal tubule is the_____________

A

Transport Maximum (Tm)

dogs: 180mg/dL
cats: 240-290mg/dL

345
Q

Why excretion of salicylic acid is increased alaklinzing the urine?

A

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

346
Q

T/F the excretion of morphine (a weak base) can be increased by acidifying the urine

A

TRUE

347
Q

T/F Na+ is freely filtered across the glomerular capillaries; therefore, the [Na+] in the tubular fluid of Bowman space equals that in plasma

A

TRUE

348
Q

T/F The reabsorption of Na+ and H20 in the proximal tubule is exactly proportional.

A

TRUE

349
Q

List causes of shift of K out and inside the cells

A
350
Q

Regarding K sparing diuretics: _________ is an antagonist of aldosterone and ____________act directly on the principal cells.

A

Spironolactone
Triamterene and amiloride

351
Q

T/F Excess anions (e.g., HC03-) in the lumen cause an increase inK+ secretion by increasing the negativity of the lumen and increasing the driving force for K+ secretion

A

TRUE

352
Q

What is the effect of PTH in phosphate reabsorption in the kidneys?

A

PTH causes phosphaturia and increased urinary cAMP

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

353
Q

T/F Fibroblast growth factor (FGF23), which is secreted by bone, stimulates Na+-phosphate cotransport in the early proximal tubule.

A

False - stimulates, it inhibits

354
Q

What is the corticopapillary osmotic gradient? How is it stablished and maintained?

A

Is the gradient of osmolarity from the cortex (300 mOsm/L) to the papilla (1200 mOsm/L) and is composed primarily of NaCl and urea.

*established by the countercurrent multiplication in the loops of henle (brings electrolytes into the interstitium) and urea recycling in the innner medullary collecting ducts
*maintained by countercurrent exchange in the vasa recta

355
Q

T/F the presence of ADH increases the size of the corticopapillary osmotic gradient

A

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

356
Q

Which are the diluting segments of the kidney

A

thick ascendinc limb of henle
early distal convoluted tubule

357
Q

What’s the normal GFR for dogs and cats

A

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

358
Q

How is the distribution of renal blood flow?

A

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

359
Q

Where are the macula densa cells located?

A

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

360
Q
A
361
Q
A
362
Q
A
363
Q

What is the glomerulotubular balance mechanism?

A
364
Q

What is the difference between the glomerulotubular balance vs the tubuloglomerular feedback?

A
365
Q

Most potent Na retaining hormone

A

ATII

366
Q

T/F AGII directly stimulates Na reabsorption in proximal tubules, loops of henle, distal tubules and collecting tubules. It stimulates Na/K ATPase pump, Na/H exchange and Na-bicarbonate co-transport

A

TRUE

367
Q
A
368
Q

What are renal mechanism for excreting a concentrated urine?

A

Presence of ADH
Hyperosmotic renal medullary interstitium

369
Q

What are the two most widely accepted human staging schemes for AKI?

A

In human medicine, 2 classification systems recently have been validated that use evidence of AKI to predict outcome in patients in the critical care setting.

*RIFLE (R-risk, I-injury, F-failure, L-loss, and E-end stage kidney disease)
* AKIN (Acute Kidney Injury Network)

They have been compared in human literature and show no statistical difference in
predicting mortality.

370
Q

Describe the 4 phases of AKI

A
  1. The initiation phase
    * The initiation phase occurs when renal blood flow decreases, resulting in cellular ATP depletion and subsequent tubular epithelial cell injury. These changes alter the ability of
    tubular epithelial cells and vascular endothelial cells to maintain normal renal function (reabsorption and secretion), as well as up-regulate a variety of chemokines and cytokines to initiate an inflammatory cascade. Intervention at this phase may prevent progression to more severe injury, but injury at this stage occurs on a subcellular level and may not be biochemically evident.
  2. Extension phase - continued hypoxia following the initial ischemic event and an inflammatory response, most prominent in the outer medullary region of the kidney. During this phase, vascular endothelial damage likely plays a key role in the continued ischemia of the tubular epithelium, as well as the inflammatory response. Cells in the outer medullary region undergo injury and death via necrosis and apoptosis. The cellular injury in this region leads to the continual reduction in GFR, whereas cells of the proximal tubule in the outer cortex, where blood flow has returned, undergo cellular repair and improve morphologically
    • biochemical derangements and clinical manifestations of disease manifest
  3. Maintenance phase -cell death and regeneration occur simultaneously –> consists of cells undergoing repair, migration, apoptosis, and proliferation to reestablish and maintain cellular and tubular integrity. The GFR usually remains stable at the level determined by the severity of the initial event. Cellular repair and reorganization results in slowly improving cellular function, setting the stage for improvement in organ function. Blood flow returns toward normal and epithelial cells establish intracellular and intercellular homeostasis. Removal of the initiating cause at this stage does not alter the existing damage but may allow for the balance to shift in favor of parenchymal regeneration
  4. The recovery phase. Improvement in GFR and tubular function; this final phase may last weeks to months
    * cellular differentiation continues, epithelial polarity is re-established, and normal cellular and organ function returns. Alternatively, renal repair can be maladaptive with inflammation, fibrosis, and vascular rarefaction leading to persistent cell and tissue malfunction and eventually CKD
371
Q

Describe the Veterinary AKI staging scheme for dogs that is a modified version of the human AKIN

A
372
Q

T/F The urine specific gravity is frequently isosthenuric (1.007 to 1.015) in cases of intrinsic failure.

A

TRUE

373
Q

Which of the phases of kidney injury is the preventable injury?

A

Between initiation and the extension phase

374
Q

IRIS AKI grading criteria

A
375
Q

What is the difference between biomarkers and functional markers/ List examples of each

A

• Functional markers (indicates decrease global kidney function mass due to kidney cell damage): creat, urea, SDMA, UO

• Biomarkers (Active Injury Markers - more useful for ongoing active injury without loss of functional kidney mass), but also helpful to localize where the injury is coming from.: NGAL, Cystatin C, Kim-1; Clusterin, NAG, IL-18 alfa-1/beta2, microglobulins”

376
Q

What is the most common pathology on necropsy of the kidneys related with use of synthetic colloids

A

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

377
Q

According to the KDIGO initiative, what are the 3 main ways to recognize AKI?

A
378
Q

How does creatinine levels behave acording to the cronicity of AKI

A
379
Q

T/F Visceral edema develops before subcutaneous edema in a patient with fluid overload

A

TRUE

380
Q

What are The traditional and most accurate assessments of renal function?

A

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

381
Q

T/F The solute excretion ratio (ER) is the mathematical equivalent of the FC for a solute and can be calculated using spot urine and plasma samples as a predictor of renal excretory function.. The ER is more clinically applicable because it eliminates the need for urinary catheter placement and timed urine collection

A

TRUE

382
Q

T/F according to a JVIM review: anuria or oliguria that persists beyond 7 days should be considered a more negative prognostic indicator than the presence of anuria or oliguria at initial presentation

A

TRUE

383
Q

Main findings on this paper

A

*Increased GFR, urine production, and decreased FC of Na were markers of renal recovery.
* The changes in FCNa and ERNa occurred in surviving dogs before any evidence of resolution of their azotemia or dialysis dependency

The FC of Na is a simple, noninvasive, and cost-effective method that can be used to evaluate recovery of renal function

384
Q

What is Cystatin C?

A

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

385
Q

T/F - mild increases in CysC may indicate early renal failure not evidenced by sCr, which suggests that CysCmay detect probable subclinical AKI

A

TRUE –> Based on this paper:

386
Q

what is the mechanism of HES-induced AKI? What were the results of a JVECC prospective randomized trial evaluating biomarkers of AKI following 6% HES or Hartmann’s solution in dogs?

A

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

387
Q

What are potential mortality predictor in cats with Acute on chronic kidney disease? (JVIM papet)

A

“In the multivariable analysis, serum phosphorous concentration remained the only significant outcome predictor.

Median sCr, urea, and phosphorous concentrations were significantly higher, and the venous blood pH was significantly lower in non- survivors compared with survivors “

388
Q

T/ FUO, presumptive pyelonephritis, and ischemic events are commonly identified etiologies for ACKD. The short-term outcome for ACKD in cats is comparable to AKI; however, long-term prognosis is guarded. Serum phosphorus is a prognostic factor for survival to discharge while sCr at discharge predicates long-term prognosis

A

TRUE

389
Q

In general, renal damage can be divided into four major structural groupings: give examples of each

A

The tubules, glomeruli, interstitium, and intra-renal blood vessels.

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

390
Q

Lack of complete recovery in the first ___ days after AKI is defined as CKD

A

90 days

391
Q

T/F A normochloremic high anion gap metabolic acidosis is common in AKI patients

A

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

392
Q

The SMART and SALT-ED trials are the largest randomized controlled trials comparing _________and _____________. Both found a _______________, in the group treated with ______________

A

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

393
Q

Justify against the use of HES for critically ill patients

A

Administration of synthetic colloids has been linked with the development of acute kidney injury
(AKI) and the need for renal replacement therapy (RRT) in ICU patients, especially those with sepsis (27, 36). Findings from meta-analyses suggest this may depend on patient cohort, but did confirm a higher risk of AKI and conflicting reports on mortality

In veterinary medicine, there is inconclusive evidence on the development of AKI in dogs and cats treated with hydroxyethyl starches (HES). The majority of the studies are retrospective, with inconsistent definitions of AKI (38–41). Extrapolating from human medicine, in most clinical situations, the risks outweigh the benefits and alternative volume replacement therapies should be used in place of HES.

394
Q

Design a fluid adminstration plan based on the ROSE concept for a patient with AKI

A

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

395
Q

T/F Furosemide is a loop diuretic with ideal pharmacokinetic properties to assess tubular function. It is not effectively filtered by the glomerulus but is bound to serum proteins and gains access to the tubular lumen via active secretion in the proximal tubule.

A

TRUE

396
Q

What is a furosemide stress test, how would you apply this clinically?

A

A furosemide stress test (1–1.5 mg/kg IV bolus) can be administered to oliguric patients that are assessed to be euvolemic or fluid overloaded to accurately determine AKI progression and need for renal replacement therapy.

*has not been studied in veterinary medicine, but extrapolating from humans, a response of 1.5ml/kg/h roughly equates to the 200 mL over the 2 h time interval.

Repeated administration of furosemide in a non-responsive patient can lead to adverse effects such as ototoxicity, which has been reported in humans.

397
Q

What are advantages of use of diuretics on AKI patients

A

“If renal replacement therapy is not available, diuretics may help control hyperkalemia by increasing
distal tubular flow and allow more liberal administration of nutrition and medications with less risk of volume overload.

The use of diuretics to increase urine output does not improve renal function. “

398
Q

Bicarbonate therapy should be considered in dogs and cats with AKI and severe metabolic acidosis (i.e., pH < ___or serum bicarbonate <___mEq/L)

A

7.1
12

399
Q

List the effects of fluid overload in the different body systems

A
400
Q

MOA of fenoldopam

A

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

401
Q

List medications that can be used to convert oligoanuria to polyuria in an AKI patient

A

Mannitol
* Good –> osmotic diuretic that decreases cellular swelling and may help to wash out obstructive casts and debris from the tubules. It may also serve as a free radi- cal scavenger
*Bad –> contraidicated in DH, overhydration, and may worsen pulmonary edema (consensus guidelines in people suggest that mannitol not be used in patients with AKI, no studies in VM)

Furosemide
*Good –> decreased renal oxygen consumption and less ischemic damage. Might help mainly for management of fluid balance, hyperkalemia, and hypercalcemia, but any putative role in amelioration of the AKI course is unproven
* Bad –> Anuric patients with minimal to no tubular flow are unlikely to have furosemide reach the site of activity, and therefore this drug is often ineffective in increasing UOP in these patients.

Fenoldopam
*A retrospective study of fenoldopam use for both dogs and cats with AKI demonstrated no improvement in survival or length of hospitalization in patients who were administered fenoldopam compared to those who were not

Diltiazem
* Good –> may improve renal blood flow through afferent arteriolar vasodilation, which may increase GFR and UOP. It may also be renoprotective by preventing the intracellular accumulation of calcium, which can trigger cellular necrosis.
*Bad –> A retrospective study evaluating the effect of diltiazem in dogs with AKI secondary to leptospirosis did not identify significant improvements in rate of reduction of serum creatinine, recovery of renal function, or survival.

402
Q

How does furosemide enters the tubular filtrate?

A

“Furosemide enters the tubular filtrate via active secretion within the proximal tubule as well as filtration of non-protein-bound furosemide across the glomerular filtration barrier

Anuric patients with minimal to no tubular flow are unlikely to have furosem- ide reach the site of activity, and therefore this drug is often ineffective in increasing UOP in these patients.”

403
Q

T/F in people, consensus guidelines suggest that furosemide only be used in early or established AKI for management of fluid balance, hyperkalemia, and hypercalcemia, but any putative role in amelioration of the AKI course is unproven

A

TRUE

404
Q

Would you recommend the use of Dopamine in an oliguric patient with AKI? Explain

A

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

405
Q

Define complicated UTI

A

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

406
Q

T/F Although UTIs can comprise mixed bacterial infections, most involve a single bacterial species

A

TRUE

407
Q

A patient with periodic UTIs with Candida spp can indicate:

A

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

408
Q

High urea concentration in the urine of dogs and cats inhibits bacterial growth, however, these microorganisms possess high urease activity

A

Staphylococcus spp, Proteus spp and Corynebacterium spp,

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

409
Q

Alkaline urine in association with UTI suggests infection with :

A

a urease-producing agent such as Proteus and Staphylococcus spp

410
Q

T/F Pyuria (>5 neutrophils/high-power field) is documented in all patients with UTI

A

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

411
Q

T/F the presence of > 104 cfu/mL bacteria in a urine sample obtained by cystocentesis from an asymptomatic patient may signify transient colonization or subclinical bacteriuria

A

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

412
Q

List suggested first line agents for simple cystitis in dogs

A

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

413
Q

____________ are resistant to all cephalosporins and TMP/S

A

Enterococci

414
Q

T/F Cephalosporins are not effective for renal or prostatic infections

A

TRUE

415
Q

List side effects of TMP/S

A

o hypersensitivity reactions that include blood dyscrasias, hepatotoxicity, polyarthropathy and skin eruptions, as well as idiosyncratic events, such as keratoconjunctivi- tis sicca (KCS).
o hypersalivation and anorexia are frequently observed following oral administration in cats

Sulfonamide hypersensitivity reactions occur > 5 days after beginning therapy, and short courses of TMP/S may be effective and safe in some dogs with simple cystitis

416
Q

TMP/S should not be used in ________________, due to increased incidence of adverse reactions in these breeds

A

Doberman Pinschers

417
Q

Urinary staphylococci (ex. Staphylococcus pseudointermedius) are becoming increasingly resistant to ___________, and initial therapy with a ___________________ should be chosen

A

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

418
Q

T/F Concurrent use of antimicrobials in a patient with an indwelling urinary catheter is discouraged, and promotes infection or colonization with multi- drug-resistant organisms”

A

TRUE

419
Q

Chloramphenicol is occasionally prescribed for prostatic infections caused by _____________. ____________________are the most commonly reported adverse events

A

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

420
Q

T/F In patients with sporadic bacterial cystitis –> If amoxicillin without clavulanic acid is not readily available, use of amoxicillin/ clavulanic acid is reasonable

A

TRUE

421
Q

For patients with recurrent bacterial cystitis –> Short (______days) durations of treatment should be considered for re-infection. Longer courses (___________ days duration) may be reasonable in persistent, and potentially relapsing infections, if factors that inhibit response to antimicrobials, such as bladder wall invasion, are suspected to be present

A

3–5 days
7– 14 days

422
Q

T/F Positive cultures indicate the need for evaluation of compliance and further diagnostic testing, to determine why the bacterium has not been eliminated, not simply a change in antimicrobial, particularly if clinical cure has been documented. Negative results could be used to help determine when to stop therapy if a long course of treatment is being used, but are not a guarantee of microbiological cure.

A

TRUE

423
Q

Which microorganism causes most of the cases of pyelonephritis?

A

Enterobacteriaceae

424
Q

In patients with pyelonephritis, what is important to consider when submitting culture specimens?

A

It is important that culture specimen submissions indicate that pyelonephritis is suspected to ensure that urine breakpoints are not applied

*Interpretation of susceptibility data should be based on antimicrobial breakpoints for serum rather than urine drug concentrations.

425
Q

T/F Evaluation for leptospirosis should be considered in culture- negative dogs suspected to have pyelonephritis by use of serological testing and PCR

A

TRUE

426
Q

What would be your antibiotic choice in patients with suspected pyelonephritis while waiting for culture and susceptibility results?

A

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

427
Q

what is the recommended treatment duration for a patient with pyelonephritis according to the ISCAID consensus

A

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

428
Q

T/F water soluble antimicrobials that are weakly alkaline with a high pKa are most likely to adequately cross the blood-prostate barrier

A

FALSE - lipid soluble

429
Q

Which antimicrobials are NOT recommended as first line therapy in bacterial prostatitis?

A

o Clindamycin and macrolides (erythromycin, azithromycin) can effectively penetrate the blood-prostate barrier, but should only be used based on culture and susceptibility test results, and not for empiric therapy because of lack of efficacy against Gram-negative bacteria (they not active against the Enterobacteriaceae

o Chloramphenicol reaches prostate fluid concentrations that are only 60% of the plasma concentrations in dogs and it is doubtful that it can reach therapeutic levels in dogs.

o The blood-prostate barrier reduces the penetration of many drugs, such as penicillins, cephalosporins, aminoglycosides and tetracyclines. This barrier is typically considered to be less intact in acute prostatitis; however, these drugs should be avoided, regardless of in vitro susceptibility data, particularly in cases of chronic prostatitis.

o Ciprofloxacin should not be used because of the unpredictable bioavailability in dogs and relatively poor prostate penetration compared to enrofloxacin”

430
Q

What is the duration of treatment recommended for bacterial prostatitis?

A

Four weeks is typically recommended for acute prostatitis

431
Q

_____________ is an option for treatment of prostatitis caused by multidrug resistant Gram-negative organisms in people (Grayson et al., 2015), and while veterinary data are lacking, this drug (dosed every 8 h) could be considered for treatment of resistant Gram-negative infections

A

Fosfomycin

432
Q

T/F Culture of urine from animals with no evidence of urinary tract disease should not be performed when there would be no indication to treat based on a positive culture result. This includes patients with comordibities, particularly those with disease such as hyperadrenocorticism and diabetes mellitus, where subclinical bacteriuria is often reported.

A

TRUE

433
Q

The isolation of a multidrug resistant bacterial species should not affect the decision whether to treat subclinical bacteriuria. Antimicrobial resistance genes are not virulence factors and resistant organisms are not more likely to cause disease than their susceptible counterparts.

A

TRUE

434
Q

List situations where urine culture may be considered in dogs and cats that do not have lower UTI signs

A
435
Q

T/F Treatment of subclinical bacteriuria caused by plaque- forming (Corynebacterium urealyticum) and urease-produc- ing (e.g. staphylococci) organisms could be considered because of their associations with encrusting cystitis and struvite urolith formation, respectively.

A

TRUE

436
Q

How would you approach a patient that develops bacterial cystitis after catheterization and requires continued catheterization

A

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

437
Q

In dogs, unlike cats, almost all struvite calculi are infection-induced, usually by :

A

Staphylococcus pseudintermedius or, less commonly, by Proteus mirabilis.

438
Q

According to the 2010 ACVIM consensus, Infection with these serovars primarily causes disease in dogs:
a. Leptospira icterohaemorrhagiae and Leptospira pomona
b. Leptospira canicola and Leptospira hardjo
c. Leptospira grippotyphosa and Leptospira Bratislava
d. Leptospira interrogans and Leptospira kirschneri

A

Leptospira interrogans and Leptospira kirschneri

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

439
Q

veterinarians should suspect leptospirosis in dogs with signs of

A

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

440
Q

T/F Polyuria and polydipsia can develop in dogs with leptospirosis in the absence of azotemia

A

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

441
Q

T/F - Leptospires replicate outside of the host and may remain viable for weeks to months in soil saturated with urine.

A

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

442
Q

T/F - MAT has good ability to predict infectious serogroups of Leptorpira

A

FALSE

443
Q

What Clinicopathologic Abnormalities Are Expected in Dogs with Leptospirosis?

A

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

444
Q

Thrombocytopenia is present in up to ___% of leptospira affected dogs

A

58%

445
Q

Are MAT recommended to predict serogroups circulating in the dog population?

A

The results of the MAT are not recommended to predict serogroups circulating in the dog population. Instead, studies involving isolation of lepto- spires from dogs are recommended for epidemiological purposes, aswellasfor selectionofantigensfor diagnostic assay development and vaccine design

The MAT is a serogroup- rather than a serovarspecific test, because antibodies to serovars within the same serogroup cross-react extensively.

446
Q

In leptospirosis, in the 1st week of illness, dogs frequently have negative MAT results, and consequently acute and convalescent phase antibody testing is recommended. Traditionally, convalescent titers for acute infectious disease diagnosis are performed _________weeks after the acute titer, although seroconversion can occur as early as ________days after dogs are brought to a veterinarian. Practitioners should wait _______days between successive titers to demonstrate seroconversion. A ___fold change in titer supports recent infection, although an increase in titer may be blunted by antimicrobial therapy

A

2–4 weeks
3–5 days
7–14 days
4-fold

447
Q

How Should Polymerase Chain Reaction (PCR) and Culture Be Used to Diagnose Canine Leptospirosis?

A
  • potential utility early in the course of untreated infection when antibody assays are frequently negative and antimicrobials have not yet been administered
  • They also can confirm active infection in animals with positive antibody test results that have a history of vaccination with leptospiral vaccines
448
Q

In the first 10 days of leptospira infection, organism numbers are highest in _________, After that time, organisms are present in highest concentration in ______

A

Blood
Urine

449
Q

Wat is the benefit of using rapid, broadly reactive antibody assays as screening tests for leptospirosis?

A

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

450
Q

What Antibiotics Should Be Used for Treatment of Canine Leptospirosis?

A
  • the consensus panel recommends treatment of canine leptospirosis with doxycycline, 5mg/ kg PO or IV q12h for 2 weeks
  • If vomiting or other adverse reactions preclude doxycycline administration, dogs with leptospirosis should be treated with ampicillin, 20mg/kg IV q6h, with dose reduction for azotemic dogs. –> Ampicillin should not be administered orally be- cause it is not reliably absorbed from the gastrointestinal tract.
  • Penicillin G (25,000–40,000U/kg IV q12h) also could be used.
  • Azithromycin also may be effective. (CONSENSUS DOES NOT COMMENT TOO MUCH ON IT THOUGH..)
451
Q

What Antibiotics Should NOT Be Used for Treatment of Canine Leptospirosis?

A
  • First generation cephalosporins appear less effective
  • leptospires are resistant to chloramphenicol.
  • Fluoroquinolones use is controversial –> Concurrent fluoroquinolone use is not recommended in dogs with leptospirosis because it contributes to antimicrobial resistance in other bacteria.
452
Q

Recovery of adequate renal function usually occurs within ____weeks of starting dialysis in leptospira patients. Sometimes ____ treatments are required before polyuria ensues and renal function begins to recover

A

2–4 weeks
only 1–3 treatments

453
Q

T/F - Treatment of humans and dogs with respiratory complications secondary to leptospirosis (ex. LPHS) with dexamethasone and desmopressin has shown some improved outcomes

A

FALSE

454
Q

What is the prognosis of dogs treated for leptospirosis?

A
  • Provided severe respiratory complications are absent, the prognosis for dogs treated early and aggressively in the course of leptospirosis with appropriate antimicrobi- al drugs and IV fluids, with or without diuretics, is good, especially when intermittent hemodialysis is available.
  • Survival rates of approximately 80% have been reported, both among dogs treated conservatively and those treated with dialysis
  • The prognosis for dogs developing se- vere respiratory complications is poorer.
455
Q

What is the expected recovery if treatment is being succesful in a patient with leptospirosis?

A
  • Successful treatment is associated with gradual return of serum urea and creatinine concentrations to reference ranges within 10–14 days (although regeneration of damaged renal tissue may continue for over 4 weeks after treatment)
  • The bilirubin concentration may decline more slowly than the activities of serum ALT and ALP.
  • Platelet counts often improve within 1 week of initiating antimicrobial treatment.
456
Q

T/F - In general, animals developing acute leptospirosis are incidental hosts and do not develop a chronic carrier state.

A

TRUE

457
Q

T/F - Positive PCR results detected in animals receiving antimicrobial therapy may reflect non- viable organisms, which would not be a zoonotic risk

A

TRUE

458
Q

T/F - Patient with confirmed leptospirosis should be treated in isolation areas

A

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

459
Q

Based on rodent model studies, when are viable organisms most likely to be present in blood or urine?

A

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

460
Q

How can urine collected from dogs with leptospirosis be inactivated?

A

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

461
Q

What vaccines currently are available for canine leptospirosis?

A

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

462
Q

How Effective Are Vaccines Against Canine Leptospirosis?

A

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

463
Q

What Is the Duration of Immunity after Vaccination?

A

They also protect for at least 12 months.

464
Q

What Adverse Effects Might Be Associated with Vaccination for Canine Leptospirosis?

A

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

465
Q

When Should Vaccination Be Recommended for Prevention of Canine Leptospirosis?

A

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

466
Q

Can Dogs That Have Recovered from Leptospirosis Be Reinfected? Is vaccination recommended after recovery?

A

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

467
Q

• Calcium oxalate, purines, and cystine uroliths form in urine with a pH _____
• struvite calculi form typically in urine with a pH _____

A

< 7
> 7

468
Q

Average dissolution time of infection-induced struvite uroliths is approximately

A

8-12 weeks

469
Q

what is d,l-methionine used for

A

urinary acidifier

470
Q

Average dissolution time of sterile struvite uroliths is approximately

A

36.2 ± 26.6 days

471
Q

Dissolution of _____________uroliths in dogs is accomplished by feeding a purine-restricted, alkalinizing diet that induces a diuresis and administering the xanthine oxidase inhibitor allopurinol (15 mg/kg PO q12h). However, ___________ uroliths may occur with allopurinol administration to dogs, especially when dietary purines are not restricted

A

Urate
Xanthine

472
Q

T/F Removal or minimally invasive procedures remain the treatment of choice for urate uroliths in cats (not medical dissolution).

A

TRUE

473
Q

Which uroliths have medical management in dogs but not in cats

A

Urate and cystine

474
Q

____________ occurs when there is a proximal renal tubular defect in reabsorption and is often present with other amino acids. Protein restricted diets and administration of ______________ is the recommended medical management in dogs

A

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

475
Q

T/F - Cats do not tolerate 2-MPG well and it is associated with GI signs, liver disease, and anemia

A

TRUE

476
Q

List minimally invasive techniques that can be considered in cases or urolithiasis in dogs and cats

A

Catheter retrieval

voiding urohydropropulsion (not successful if patient presents with urethral obstruction)
* Sizes of uroliths that may be retrieved with this technique are
o ~ 1 mm in male cats, up to 5 mm in female cats
o ~ 1–3 mm in male dogs, and up to 10 mm in female dogs

Transurethral cystoscopic stone removal (with or without use of laser lithotripsy) - (not recommended in male cats)

Mini-laparotomy-assisted cystoscopic stone removal/percutaneous cystolithotomy (PCCL) - (minimally invasive procedure of choice for male dogs and cats because the diameter of the male urethra limits insertion of a cystoscope with operating channel)

477
Q

List minimally invasive techniques that can be considered in cases or ureteral obstruction in dogs and cats

A

Nephrostomy tube
Ureteral stent
SUB

478
Q

> 90% of feline upper tract stones are

A

calcium oxalate

479
Q

T/F After 7 days of an ureteral obstruction the GFR is permanently diminished by 35%, and after 2 weeks by 54%

A

TRUE

480
Q

Describe medical management of an ureteral obstruction

A

Fluid diuresis, a ureteral muscle relaxer (alpha-adrenergic blockade), and mannitol (0.25 g/kg bolus IV then 1 mg/kg/min CRI for 24 hours)

As long as the patient is not overhydrated, hyperkalemic, oliguric, or showing evidence of progressive renal pelvic dilation on daily imaging

success 8–13% of cases, stones move into different positions to allow urine to pass, but the stone itself not actually moving out of the ureter - high risk of re-obstruction

If medical management fails to encourage stone passage after 24–48 hours  consider: nephrostomy tube placement, ureteral stenting, and the placement of a subcutaneous ureteral bypass (SUB) devices

481
Q

This procedure could be indicated to quickly relieve an ureteral obstruction and determine whether adequate renal function remains before prolonged anesthesia for ureteral surgery, ureteral stent or SUB device placement can be performed. It can also be considered if stent placement is not successful, because the ureter can experience severe edema and spasm and will be acutely obstructed, requiring another mechanism of drainage

A

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

482
Q

Explain the patogenesis of Feline Lower Urinary obstruction

A

Cause: physical obstruction (calculus, urethral plug, stricture, neoplasia) vs functional obstruction (idiopathic 50% of cases)

Idiopathic (FIC)–> Appears to be a sterile inflammatory process–> maybe a sympathetic and hypothalamic-pituitary-adrenal imbalance brought about by stressful situations. Results in impaired blood flow and release of inflammatory mediators which cause edema, smooth muscle spasm, and pain within the LUT.

In general –> Pressure necrosis and mucosal injury will occur -> subsequent reduction of GFR.
Within 24–48 hours of obstruction, the kidney’s excretory ability ceases, resulting in an accumulation of BUN, creatinine, phosphorus, potassium, and H in the blood.
Uremia -> depression, nausea, vomiting, and anorexia.
Decreased intake + potential GI losses -> dehydration -> hypovolemia
Metabolic acidosis -> denaturing of proteins, enzymatic dysfunction, and catecholamine hyposensitivity.

483
Q

T/F - A study suggest that use of a 3.5 Fr urinary catheter may be associated with less risk of immediate reobstruction when compared to 5 Fr

A

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

484
Q

What is the definition of postobstructive diuresis and the proposed mechanisms

A

> 2ml/kg/h

Accumulation of osmotically active substances in the blood (osmotic diuresis)
tubular epithelial dysfunction
medullary washout
antidiuretic hormone resistance
increases in natriuretic factors brought about during the obstructive process

Proposed incidence –> 37% when corrected for rate of fluid administration

485
Q

What is the reported recurrence rate of feline urethral obstruction and the potential factor affecting it?

A

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

486
Q

T/F it appears that fluid type does not have a clinically relevant impact on resolution of metabolic derangements or patient outcome in cats with UO

A

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

487
Q

What’s the material of each of the following

A

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

A»»D reactivity

488
Q

Why polyvinyl catheters are not ideal for the initial unblocking process?

A

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

489
Q

T/F - polytetrafluoroethylene and polyurethane catheters carry the benefit of being firmer at room temperature to facilitate initial unblocking efforts, but then soften when warmed to body temperature (meaning they can be left in place).

A

TRUE

490
Q

Medications often used for the purpose of providing urethral relaxation include _______________________, which all function as alpha-1 antagonists to cause smooth muscle relaxation

A

phenoxybenzamine, acepromazine, and prazosin

491
Q

What is the disadvantage of using phenoxybenzamine to provide urethral relaxation?

A

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

492
Q

T/F Acepromazine and prazosin only seems to affect the preprostatic and prostatic urethra, and don’t appear to have a discernable effect on postprostatic or the penile urethra in cats

A

TRUE

493
Q

T/F - only the proximal 1/4–1/3 of the feline urethra is smooth muscle, with the remainder as skeletal muscle. As such, alpha-1 antagonists will have minimal effects on the distal (especially penile) urethra where the majority of obstructions are believed to occur

A

TRUE

494
Q

What is the outside diameter of a 12Fr urinary catheter?

A

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

495
Q

T/F The use of hydrophilic urinary catheters with silver or chlorhexidine coating may help to prevent biofilm formation in urinary catheters

A

TRUE

496
Q

Decreased sodium chloride delivery to the macula densa will cause ___________(↑↓) afferent arteriole resistance

A

Decrease

497
Q

Renin is released from the JGA in response to changes in:

A

AA pressure
Decreased NaCl delivery to the macula densa

498
Q

T/F - A diuretic that prevents Na reabsorption in the LOH will induce more natriuresis than one that acts more proximally

A

TRUE

499
Q

All diuretics, except ______________ are active at the tubular lumen and must reach their site of action via filtration or secretion

A

Spironolactone

500
Q

_____________ transporters are responsible for 80 to 90% of the glucose reabsorption in the PT

A

SGLT2

501
Q

Loop diuretics act in the NKCC pump competing with ____ for its binding site on the carrier.

A

Chloride

502
Q

Furosemide is ___% protein bound and a weak organic acid. It is therefore minimally filtered at the level of the glomerulus, but instead secreted through the ________ transporter in the _____.

A

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

503
Q

List the mechanisms of mannitol to reduce increased intracraneal pressure

A

Decreased IC water
Rheologic properties
free radical scavenger

504
Q

List properties of mannitol that could help a patient with AKI

A

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

505
Q

These two diuretics are secreted thorugh the OAT in the proximal tubule and compete for a Cl binding site in a cotransporter.

A

Loop diuretics
Thiazides

506
Q

T/F - Thiazides can result in Ca retention

A

TRUE

507
Q

This diuretic is associated with minimal potassium wasting and may reduce myocardial remodeling

A

Spironolactone

508
Q

What are the types of renal tubular acidosis?

A

1) Distal tubular acidosis (Classic or type 1)
* Defective acid excretion in the presence of normal GFR
* alpha intercalated cells are unable to excrete H ions to the tubular lumen
* K is excreted instead, dragged by the negative lumen (can cause hypokalemia)
* Since urine pH>6ish -> prompt to nephrolithiasis and nephrocalcinosis

2) Proximal tubular acidosis (type 2)
* PT fails to reabsorb HCO3-
* However, distal nephron functions normally and urine can still be acidified
* characterized by hyperchloremic metabolic acidosis
* can be accompanied by other abnormalities of the proximal tubular function (Fanconi syndrome)

3) Combined (Type 3)
*Combined type 1 and 2 - rare

4) Hyperkalemic (type 4)
* caused by decreased aldosterone release or activity (hypoaldosteronism)
* decreases excretion of H and K –> then hyperkalemia and acidosis

509
Q

What is the hallmark of distal renal tubular acidosis

A

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