Intro to diuretics and renal disease Flashcards
What are the 3 common uses of diuretics?
- control ECF volume
- increase urine volume output
- lower ECF volume
What conditions would result in needing to control ECF volume?
- hypertension: non-renal failure induced elevations in ECF
- edema: trauma, congestive heart failure
What do most diuretics target?
Na excretion/resorption
- since Na stays in the lumen, so does water
Why does decreased resorption of other electrolytes occur with diuretic use?
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)
Diuretics are considered to be potassium ______
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+
What diuretics are not K+ wasting?
Those that target Na resorption by the principle cells of the distal tubules and collecting ducts
Osmotic diuretics
Increase tubular osmolarity
- use with excess glucose or urea
- ex: mannitol
Loop blocker diuretics
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
Thiazide diuretics
Inhibit Na Cl cotransport by targeting the Na-Cl co transporter on the apical membrane of early distal tubules
- ex: hydrochlorothiazide
Carbonic anhydrase inhibitors
Inhibit H secretion and HCO3 reabsorption = blocking Na reabsorption
- disadvantage: can cause acidosis due to loss of bicarb
- used to manage HYPP
- ex: acetazolamide
Aldosterone antagonist
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
Na channel blocker
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
Kidney is the primary organ responsible for long term maintenance of ___
pH
What are the 6 main functions of the kidney?
- 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
Uremia
Accumulation of nitrogenous waste products
- urea, creatinine, ammonia
Hyperkalemia causes ______
Arrhythmias, neuromuscular dysfunction
Acidosis
Affects CNS function and all cell processes
- retention of H and organic acids, loss of bicarb
Hypertension or hypotension
Failure to excrete or conserve sodium and water
- failure to produce renin = no angiotensin
- edema or dehydration
What 2 hormones are produced by the kidney?
- renal erythropoietic factor: absence leads to anemia
- 1,25 dihydroxycholecaliferol (Vit D): absence leads to osteomalacia
Does renal disease have subclinical signs?
NO
- kidney can be deteriorating for a while without clinical signs appearing
Renal disease clinical signs
Often vague
- general malaise
- inappetence
- polyuria/polydipsia
- weight loss
- weak/lethargy
- hypertension
- edema
Prerenal disease will typically result in _______
Diminished renal blood flow
What are the 3 main causes for diminished RBF?
- volume loss: diminished renal perfusion (diarrhea, hemorrhage, etc)
- volume redistribution: endotoxemia, septicemia, 3rd space sequestration
- cardiovascular failure: diminished renal perfusion (myocardia, valve disease, etc)
Dehydration is typically a ______ issue
Prerenal
SpGr should be ____ in dehydration
High
How does the macula densa react during states of mild dehydration?
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
Why does BUN increase during dehydration?
Low flow states cause increased time for reabsorption of urea
- ADH induced carrier proteins facilitate urea reabsorption from medullary collecting tubules
High urine SpGr with a high BUN and Cr indicates ____
Pre-renal azotemia
High BUN and Cr with a lower urine SpGr indicates _____
Renal failure
Glomerulonephritis, vasculitis, and chronic hypertension are all forms of _____
Renal disease
Changes in the _______ only occurs in disease states
Filtration coefficient
Chronic hypertension causes a thickening of the _____
Glomerular basement membrane = thicker diffusion barrier opposing fluid flow
Acute glomerulonephritis
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
Chronic glomerulonephritis
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
Hypertension is more commonly _____ to renal disease
Secondary
- failure to control hypertension leads to worsening of renal function due to progressive glomerulosclerosis
What is the name of the carrier molecule found in the brush border membrane of the proximal tubules that facilitates Ca transport?
Phosphotidyl inositides
PI will also bind to ______
Aminoglycoside antibiotics
- ex: genamicin
What negative impact does aminoglycoside have on the cell?
Impacts mitochondrial function resulting in a decrease in ATP formation
- Na K ATPase pump fails = glucosuria, proteinuria, increased fractional excretion of electrolytes
PTH secretion is determined by the state of _______
Calcium repletion or depletion
Decreased Ca intake leads to ___ PTH synthesis
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
Why is additional calcium given to horses undergoing gentamicin treatment?
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
What are the first clinical signs of aminoglycoside toxicity?
- proteinuria
- glucosuria
What does PGE do in low flow states?
Maintains RBF by dilating afferent arterioles
In severe low flow states, efferent arteriolar constriction is ameliorated by production of _______
Vasodilatory prostaglandins (PGE, PGI) - ensures oxygen delivery to renal medulla
What is the cause of poor tubular perfusion and hypoxia?
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
Interstitial nephritis
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
NSAID toxicity is a form of ____
Renal disease
- usually affects distal tubules
Pyelonephritis
Renal interstitial injury caused by bacterial infection
- E. coli
What are 2 conditions that may affect the normal flushing of bacteria from the bladder?
- inability of bladder to empty completely
- existence of obstruction of urine outflow
Vesicouretal reflux
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
Ascending pyelonephritis begins in the _____
Renal medulla
- affected patients have difficulty concentrating the urine
Glomeruli are more susceptible to _____ pathogens
Blood borne
- due to large CO that goes to the kidney
- could alter GFR before affecting tubular function
Nephrolith
Diminished filtration affected nephrons
- few % decrease in nephrons and GFR
- may not be clinically detectable
- post renal disease
Ureter
Diminished filtration affected kidney
- 50% decrease in functional nephrons and GFR
- post renal
Urethra
Diminished filtration of both kidneys
- 100% decrease in functional nephrons and GFR
- quickly deadly
- post renal
Why does an upward drift of BUN and Cr occur over the lifetime without renal disease?
Because an animal can lose up to almost half of the nephrons normally
What also decreases with age?
Muscle mass
- means that as you lose nephrons, you also lose the amount of Cr that needs to be excreted
Why does urea and Cr accumulate in proportion to the number of nephrons that have been destroyed?
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)
Is RBF and GFR internally regulated based on creatinine concentrations or electrolyte concentrations?
Electrolyte concentrations
The effect of nephron loss (without subsequent muscle mass loss) on creatinine
- 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
SpGr is a measure of _____
Osmolarity
- is a refraction of the amount of dissolved solute in a solution
- normal: 1.002-1.045
Urine protein/creatinine
- <0.5 dogs
- <0.4 cats
- <0.3-0.2 horses
GGT
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
Serum GGT
Reflects GGT from hepatic biliary cells
GGT/Cr ratio formula
(UrGGT(U/L))/(UrCr(Mg/dl) * 0.01)
Elevated LDH/Cr ratios in the urine reflect ______
Distal nephron damage
Enzyme levels are difficult to obtain, and are usually standardized to _____
Creatinine concentration
- expressed as per g Cr
- most common enzyme in the horse is GGT
Are values of GGT up to 100 g Cr worrisome?
No, due to the high sensitivity this is to be expected
- anything above 100 is concerning
Urine prot/cr ratio formula
Urpro/Urcr
Sodium fractional excretion
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
FE formula
(Pcr/Ucr)(Ux/Px) * 100
Creatinine clearance formula
(Ucr * V) / Pcr
- is also an approximation of GFR
