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Physiology > Intro to diuretics and renal disease > Flashcards

Intro to diuretics and renal disease Flashcards

1
Q

What are the 3 common uses of diuretics?

A
  • control ECF volume
  • increase urine volume output
  • lower ECF volume
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2
Q

What conditions would result in needing to control ECF volume?

A
  • hypertension: non-renal failure induced elevations in ECF

- edema: trauma, congestive heart failure

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3
Q

What do most diuretics target?

A

Na excretion/resorption

- since Na stays in the lumen, so does water

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4
Q

Why does decreased resorption of other electrolytes occur with diuretic use?

A

Since water remains in the tubules, there is an increased flow rate through the tubules which leads to diminished resorption of electrolytes (Ca, Mg, etc) that rely on a concentration gradient for passive reabsorption
- do not see an increase in the concentration of other electrolytes that would normally occur with reabsorption of Na and water (so, no increase in concentration = no concentration gradient established)

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5
Q

Diuretics are considered to be potassium ______

A

Wasting
- increased Na, water, and flow rate prevents an increase in K concentration at the level of the distal tubule and collecting duct, promoting more rapid excretion of K+

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6
Q

What diuretics are not K+ wasting?

A

Those that target Na resorption by the principle cells of the distal tubules and collecting ducts

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7
Q

Osmotic diuretics

A

Increase tubular osmolarity

  • use with excess glucose or urea
  • ex: mannitol
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8
Q

Loop blocker diuretics

A

Inhibit Na-K-Cl cotransport

  • blocks concentrating and diluting ability
  • increase urine output of Na, Cl, K, etc
  • increase quantities of solutes delivered to distal parts of nephrons, which act as osmotic agents
  • disrupt countercurrent multiplier system by decreasing absorption of ions from Henle into the medullary interstitium
  • ex: furosemide
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9
Q

Thiazide diuretics

A

Inhibit Na Cl cotransport by targeting the Na-Cl co transporter on the apical membrane of early distal tubules
- ex: hydrochlorothiazide

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10
Q

Carbonic anhydrase inhibitors

A

Inhibit H secretion and HCO3 reabsorption = blocking Na reabsorption

  • disadvantage: can cause acidosis due to loss of bicarb
  • used to manage HYPP
  • ex: acetazolamide
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11
Q

Aldosterone antagonist

A

Blocks aldosterone receptor in the cortical collecting tubule principle cells = decreased reabsorption of Na and secretion of K (leading to a decrease in excretion of K)
- ex: spironolactone

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12
Q

Na channel blocker

A

Blocks Na entry into the Na channels of the apical membrane of the collecting tubule cells that were inserted under the influence of aldosterone

  • leads to decreased activity of Na K ATPase pump, reducing secretion of K
  • ex: amiloride
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13
Q

Kidney is the primary organ responsible for long term maintenance of ___

A

pH

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14
Q

What are the 6 main functions of the kidney?

A
  • excretion of metabolic waste products
  • regulation of acid-base balance
  • control of arterial pressure
  • regulation of water and electrolyte excretion
  • secretion, metabolism, and excretion of hormones
  • excretion of foreign chemicals
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15
Q

Uremia

A

Accumulation of nitrogenous waste products

- urea, creatinine, ammonia

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16
Q

Hyperkalemia causes ______

A

Arrhythmias, neuromuscular dysfunction

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17
Q

Acidosis

A

Affects CNS function and all cell processes

- retention of H and organic acids, loss of bicarb

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18
Q

Hypertension or hypotension

A

Failure to excrete or conserve sodium and water

  • failure to produce renin = no angiotensin
  • edema or dehydration
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19
Q

What 2 hormones are produced by the kidney?

A
  • renal erythropoietic factor: absence leads to anemia

- 1,25 dihydroxycholecaliferol (Vit D): absence leads to osteomalacia

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20
Q

Does renal disease have subclinical signs?

A

NO

- kidney can be deteriorating for a while without clinical signs appearing

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21
Q

Renal disease clinical signs

A

Often vague

  • general malaise
  • inappetence
  • polyuria/polydipsia
  • weight loss
  • weak/lethargy
  • hypertension
  • edema
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22
Q

Prerenal disease will typically result in _______

A

Diminished renal blood flow

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23
Q

What are the 3 main causes for diminished RBF?

A
  • volume loss: diminished renal perfusion (diarrhea, hemorrhage, etc)
  • volume redistribution: endotoxemia, septicemia, 3rd space sequestration
  • cardiovascular failure: diminished renal perfusion (myocardia, valve disease, etc)
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24
Q

Dehydration is typically a ______ issue

A

Prerenal

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25
Q

SpGr should be ____ in dehydration

A

High

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26
Q

How does the macula densa react during states of mild dehydration?

A

Induces afferent arteriolar dilation and release of renin from juxtaglomerular cells results in efferent arteriolar constriction
- both work to preserve GFR and glomerular hydrostatic pressure, ensuring filtration/elimination of Cr

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27
Q

Why does BUN increase during dehydration?

A

Low flow states cause increased time for reabsorption of urea
- ADH induced carrier proteins facilitate urea reabsorption from medullary collecting tubules

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28
Q

High urine SpGr with a high BUN and Cr indicates ____

A

Pre-renal azotemia

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29
Q

High BUN and Cr with a lower urine SpGr indicates _____

A

Renal failure

30
Q

Glomerulonephritis, vasculitis, and chronic hypertension are all forms of _____

A

Renal disease

31
Q

Changes in the _______ only occurs in disease states

A

Filtration coefficient

32
Q

Chronic hypertension causes a thickening of the _____

A

Glomerular basement membrane = thicker diffusion barrier opposing fluid flow

33
Q

Acute glomerulonephritis

A

Accumulation of percipitated antigen-antibody complexes in the glomerular membrane, secondary to infection
- causes infammation, leading to prostaglandin synthesis = increased permeability of glomerular filtration barrier allowing proteins, RBCs to leak thru

34
Q

Chronic glomerulonephritis

A

Retention of albumin and antigen/antibody complexes within the basement membrane

  • leads to progressive thickening of BM, mesangial cell proliferation, and infiltration of glomeruli by fibrous tissue
  • filtration coefficient becomes greatly reduced
35
Q

Hypertension is more commonly _____ to renal disease

A

Secondary

- failure to control hypertension leads to worsening of renal function due to progressive glomerulosclerosis

36
Q

What is the name of the carrier molecule found in the brush border membrane of the proximal tubules that facilitates Ca transport?

A

Phosphotidyl inositides

37
Q

PI will also bind to ______

A

Aminoglycoside antibiotics

- ex: genamicin

38
Q

What negative impact does aminoglycoside have on the cell?

A

Impacts mitochondrial function resulting in a decrease in ATP formation
- Na K ATPase pump fails = glucosuria, proteinuria, increased fractional excretion of electrolytes

39
Q

PTH secretion is determined by the state of _______

A

Calcium repletion or depletion

40
Q

Decreased Ca intake leads to ___ PTH synthesis

A

Increased

  • stimulates PI synthesis and incorporation into the brush border membrane = increased aminoglycoside uptake, increasing toxicity risk
  • opposite is true for increased Ca synthesis/supplementation
41
Q

Why is additional calcium given to horses undergoing gentamicin treatment?

A

Ca competitively inhibits aminoglycoside binding to PI receptors and can also displace already bound gentamicin from the BBM vesicles, leading to decreased uptake and diminished toxicity

42
Q

What are the first clinical signs of aminoglycoside toxicity?

A
  • proteinuria

- glucosuria

43
Q

What does PGE do in low flow states?

A

Maintains RBF by dilating afferent arterioles

44
Q

In severe low flow states, efferent arteriolar constriction is ameliorated by production of _______

A 
Vasodilatory prostaglandins (PGE, PGI)
- ensures oxygen delivery to renal medulla
45
Q

What is the cause of poor tubular perfusion and hypoxia?

A

Sympathetic tone overrides vasodilatory effects of PGE and the autoregulatory mechanism fails as afferent arteriolar constriction occurs
- causes the macula densa to contstrict afferent arterioles which further reduces GFR

46
Q

Interstitial nephritis

A

Primary or secondary disease of the renal interstitium

  • results from vascular, glomerular, or tubular damage
  • could destroy individual nephrons, or cause primary damage to renal interstitium
47
Q

NSAID toxicity is a form of ____

A

Renal disease

- usually affects distal tubules

48
Q

Pyelonephritis

A

Renal interstitial injury caused by bacterial infection

- E. coli

49
Q

What are 2 conditions that may affect the normal flushing of bacteria from the bladder?

A
  • inability of bladder to empty completely

- existence of obstruction of urine outflow

50
Q

Vesicouretal reflux

A

Condition in which urine is propelled up one or both ureters during micturition

  • due to failure of bladder wall to occlude the ureter during micturition
  • urine could carry bacteria into the renal pelvis and medulla
51
Q

Ascending pyelonephritis begins in the _____

A

Renal medulla

- affected patients have difficulty concentrating the urine

52
Q

Glomeruli are more susceptible to _____ pathogens

A

Blood borne

  • due to large CO that goes to the kidney
  • could alter GFR before affecting tubular function
53
Q

Nephrolith

A

Diminished filtration affected nephrons

  • few % decrease in nephrons and GFR
  • may not be clinically detectable
  • post renal disease
54
Q

Ureter

A

Diminished filtration affected kidney

  • 50% decrease in functional nephrons and GFR
  • post renal
55
Q

Urethra

A

Diminished filtration of both kidneys

  • 100% decrease in functional nephrons and GFR
  • quickly deadly
  • post renal
56
Q

Why does an upward drift of BUN and Cr occur over the lifetime without renal disease?

A

Because an animal can lose up to almost half of the nephrons normally

57
Q

What also decreases with age?

A

Muscle mass

- means that as you lose nephrons, you also lose the amount of Cr that needs to be excreted

58
Q

Why does urea and Cr accumulate in proportion to the number of nephrons that have been destroyed?

A

Urea and creatinine depend on glomerular filtration for excretion, with no regulation within the tubules
- excretion rate is equal to the rate at which it is filtered (Cr)

59
Q

Is RBF and GFR internally regulated based on creatinine concentrations or electrolyte concentrations?

A

Electrolyte concentrations

60
Q

The effect of nephron loss (without subsequent muscle mass loss) on creatinine

A
  • decreases filtration capacity and overall Cr clearance
  • Cr concentration doubles
  • new equilibrium is established at a higher serum creatinine, so nephron loss does not result in a continuous accumulation of serum Cr
61
Q

SpGr is a measure of _____

A

Osmolarity

  • is a refraction of the amount of dissolved solute in a solution
  • normal: 1.002-1.045
62
Q

Urine protein/creatinine

A
  • <0.5 dogs
  • <0.4 cats
  • <0.3-0.2 horses
63
Q

GGT

A

Cleaves C-terminal glutamyl groups from amino acids and transfers them to another peptide or amino acid

  • is expressed on membranes of proximal renal tubular cells where amino acids are reabsorbed
  • proximal tubular injury or aminoglycoside toxicity causes GGT to be released
64
Q

Serum GGT

A

Reflects GGT from hepatic biliary cells

65
Q

GGT/Cr ratio formula

A

(UrGGT(U/L))/(UrCr(Mg/dl) * 0.01)

66
Q

Elevated LDH/Cr ratios in the urine reflect ______

A

Distal nephron damage

67
Q

Enzyme levels are difficult to obtain, and are usually standardized to _____

A

Creatinine concentration

  • expressed as per g Cr
  • most common enzyme in the horse is GGT
68
Q

Are values of GGT up to 100 g Cr worrisome?

A

No, due to the high sensitivity this is to be expected

- anything above 100 is concerning

69
Q

Urine prot/cr ratio formula

A

Urpro/Urcr

70
Q

Sodium fractional excretion

A

Measure of proximal tubular function and ability to resorb essential solutes that are filtered

  • NaFE should be <0.8-1%
  • tubular dysfunction will increase this
71
Q

FE formula

A

(Pcr/Ucr)(Ux/Px) * 100

72
Q

Creatinine clearance formula

A

(Ucr * V) / Pcr

- is also an approximation of GFR

Physiology (33 decks)

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