chapter 32 diuretics, kidney diseases Flashcards
What do diuretics generally do in terms of
1) urinary output
2) solutes
3) renal tubular absorption
4) water
1) increase the rate of urine output
2) increase urinary excretion of solutes (na and cl)
3) decrease renal tubular absorption (increased na output=naturesis)
4) water loss in urine secondary to inhibition of tubular reabsorption of na (other solutes may be lost as well)
what is most common use of diuretics
reduce extracellular fluid volume, especially in diseases such as edema and HTN
name 5 compensatory responses to chronic diuretic usage
*when do these compensatory mechanisms occur?
1) decreased ECF volume2) reduces arterial pressure and the 3)GFR leading to 4)increased renin and 5)angiotensin II
* these compensatory mechanisms generally occur only after decreases in BP and ECF volume have occured
What is mechanism of action of osmotic diuretics
decrease water reabsorption by increasing the osmotic pressure of the tubular fluid
name 3 major ingredients of osmotic diuretics, and how do they exert their effects
1)mannitol 2)urea 3)sucrose
exert increased osmotic pressure in tubules, which reduces water reabsorption, pulling water into urine via osmosis, as mannitol, urea, and sucrose are generally not reabsorbed
1) In diabetes, what sugar level in the plasma acts to cause osmotic diuresis of excess urine?
2) what are hallmark symptoms of DM?
1) 250mg/dl exceeds tubular reabsorption of glucose, resulting in excess glucose in filtrate(urine) which pulls water into filtrate (urine) via osmosis
2) polyuria, polydypsia
How do Loop Diuretics exert their effects?
decrease active 1na-2cl-1k cotransporter that normally causes reabsorption in the luminal membrane of the epithelial cells in the thick ascending loop of henle. Blocking the na, cl, k, cotransporter results in increased output of na, cl, and k in filtrate (urine) which pulls water via osmosis, and this causes disruption of countercurrent multiplication system by decreasing osmolarity of renal interstitium (normally salty), so kidneys cannot dilute or concentrate urine.
Name 3 examples of loop diuretics
1)furosimide 2)ethacynic acid 3)bumetanide
with loop diuretics, why is urinary 1)dilution and 2) concentration impaired
1) decreased solutes in medullary interstitum causes more solutes to be excreted than reabsorbed in LOH, and water follows the osmotic gradient of the solutes
2) reabsorption of water in collecting ducts is impaired
how much of GFR is delivered to urine after administration of loop diuretics
20-30% of GFR, causes UOP to be increased by 25% for at least a few minutes
1) How do thiazide diuretics work
2) name a common thiazide diuretic
3) how much of GFR can pass into urine
1) inhibit na/cl cotransporter, stoping reabsorption in the lumenal membrane (urine side) of early distal convoluted tubule
2) chlorothiazide
3) 5-10% of GFR passes into urine (which is same amount of Na normally reabsorbed in DCT)
1) How do carbonic anhydrase inhibitors work?
2) name an example
3) by decreasing HCO3 reabsorption and H secretion, what happens to na reabsorption
4) what do carbonic anhydrase inhibitors cause
inhibits carbonic anhydrase enzyme, which is necessary for reabsopriton of HCO3 PCT(primary effect) and intercalated cells of collecting tubule (minimal)
2) acetazolamide
3) na reabsorption decreases because in PCT na/H countertransport is coupled to HCO3 reabsorption and H secretion, resulting in more Na in urine that exerts osmotic diuretic effects by pulling water into urine
4) cause acidosis because of loss of HCO3 in urine
1) how do mineral corticoid receptor antagonists work
2) what happens to potassium with this type of diuretic
3) name 2 examples of this type of diuretic
1) compete with aldosterone for receptor binding sites in collecting tubule epithelial cells causing decrease na reabsorption in collecting tubules, and potassium secretion into collecting tubules, resulting in na remaining in tubules (urine side) pulling more water and na into urine
2) because aldosterone is blocked, K secretion does not happen, and K moves into ECF
3) sprinolactone, eplerenone
1) How do Na channel blockers work as diuretics
2) are Na channel blockers K sparing?
3) name 2 examples of Na channel blockers
1) inhibit na reabsorption and K excretion in collecting tubules, blocking na channels of lumenal membrane (urine side) and blocking na/k/atpase pump on basolateral side (blood side)=reduced K into cells, and decreased K into urine
2) na channel blockers are K sparing
3) amiloride and trianterene
Describe acute kidney disease
abrupt loss of kidney function within a few days-can be reversible.
describe acute renal failure
severe acute kidney injury where the kidneys may stop working necessitating dialysis
describe chronic kidney disease
progressive loss of function of nephrons that gradually decreases renal function
describe pre renal acute kidney injury, give some examples
prerenal=decreased blood supply to kidney, with issue originating in area before kidneys-heart failure with low CO and BP, severe hemorrhage
describe intrarenal acute kidney injury, give some examples
abnormalities inside of kidney such as blood vessels, glomeruli, and/or tubules
1) describe post renal acute kidney injury
2) give examples
1) obstruction of urinary collecting system anywhere from the calyces to outflow from bladder
2) examples-stones (urate, calcium, cystine)
How much blood supply do kidneys normally receive
1100ml/min or 20-25% of CO
why do kidneys receive such high blood flow volumes
provide enough plasma for the high rates of GFR needed for effective regulation of body fluid volumes and solute concentrations
what happens with decreased renal blood flow
1)decreased GFR 2)decreased urine output of solutes and water, which accumulate in the body
As long as blood flow does not fall to ____% of normal, AKI can usually be _____ if the cause of ischemia is corrected before damage to renal cells has occurred
20-25%, reversed
what are protective mechanisms in kidneys during times of reduced blood flow
GFR and filtered nacl, water and other electrolytes is reduced which decreases the amount of reabsorption (reabsorption requires the most energy), and thereby reduces the amount of O2 consumption
in times of no blood flow to kidney, what happens to renal cells and tubular epithelial cells
- below 20-25% of blood flow, renal cells become hypoxic causing damage and death of renal cells and tubular epithelial cells.
- ischemia >a few hours causes prerenal failure to evolve into intrarenal failure
name some examples of pre renal failure 4 categories
- intravascular volume depletion (hemorrhage, diarrhea, vomiting, burns)
- cardiac failure (MI, valvular damage)
- Peripheral vasodilation/hypotension (anaphylactic shock, anesthesia, sepsis)
- Renal artery stenosis, embolism, thrombosis of renal artery or vein
name some examples of intrarenal acute kidney injury
- small vessel and/or glomerular injury (polyarteritis nodosa), cholesterol emboli, malignant hypertension, acute glomerular nephritis
- tubular epithelial injury (tubular necrosis) ischemia, toxin ingestion
- renal interstitial injry (acute polynephritis, acute allergic interstitial nephritis)
intrarenal acute kidney injury-what is it
abnormalities that originiate in kidney and abruptly diminish urine output
describe acute glomerulonephritis
damage to glomeruli resulting from infective process occurring outside of kidney, usually from group A beta strep. Antibody antigen complexes from insoluble immune complex that are entrapped in glomerulus in basement membrane of glomeruli, either blocking the glomeruli or increasing glomeruli permeability beyond normal causing protein and RBCs to leak from blood into urine. Can be self limiting, or progress to CRF
Describe acute tubular necrosis-what is damaged and what are 2 major reasons
destruction of epithelial cells in the tubules, caused by 1)severe ischemia and inadequate supply of O2 and nutrients to tubular epithelials, and 2)poisons
In renal ischemia that causes acute tubular necrosis, describe pathology, and what is most common cause
damaged tubular epithelial cells slough off, and plug nephrons, and nephrons that are plugged fail to excrete urine even when renal blood flow is restored to urine, even after blood flow is restored to normal-most common-circulatory shock
Describe acute tubular necrosis caused by toxins-what are common toxins
tubular epithelium on basement membrane are damaged and slough off and plug tubules, sometimes basement membrane is destoryed, can repair itself in some cases in 10-20 days
-carbon tetrachloride, heavy metals (mecury and lead) ethylene glycol (antifreeze), insecticides, tetracyclines, cis-platinum (cancer med)
Describe post renal AKI-what happens if only one kidney is effected, how long before irreversible damage occurs, and what are 3 causes
blockage or partial blockage of urine flow even if blood supply and kidney function is initially normal.
if only one kidney is effected, other kidney will compensate and no huge changes in body fluid composition
-if issue is corrected in a few hours, no major issues
-chronic blockage of urinary tract lasting several days or weeks can cause irreversible kidney damage
-common causes-blood clots or stones obstructing ureters or renal pelvises, 2)bladder obstruction 3)obstruction of urethra
Name 4 major physiological effects of acute renal injury
retention of water
accumulation of waste products
accumulation of electrolytes in blood and ECF (especially K)
metabolic acidosis(can further cause hyperkalemia)
how long after AKI will a patient die if anuric
8-14 days unless dialysis is initiated
what defines CKD, when is CKD clincally apparent
- kidney damage/decreased kidney function that persists at least 3 months
- functional nephrons 70-75 percent of normal-no clinical symptoms
- ECF and electrolytes until functional nephrons drop below 20-25 percent
Name two adaptions to loss of functioning nephrons
what happens over time
what is best medication to use to prevent this
1) hypertrophy of remaining nephrons
2) decrease in vascular resistance and tubular reabsorption in surviving neprhons-functional vasodilation and increased pressure to glomerulus
* this adaption leads to further injury of surviving nephrons over time however due to sclerosis of glomeruli and arteroiles from increased pressure-use ace inhibitor to slow this process (lower glomerular hydrostatic pressure and arterial pressure)
What are the most common causes of ESRD (5)
what is an important risk factor seen with two of these
1) DM 2)HTN 3)glomerulonephritis 4)Polycystic kidney disease 5)other/unknown
* excessive weight gain as seen with DM and HTN most important main risk factor for ESRD with HTN and DM
Describe the vicious circle with primary kidney disease
primary kidney disease–>decreased nephrons–>hypertrophy and vasodilation of surviving neprhons–>increase in arterial pressure–>increase in glomerular pressure and filtration rate–>glomerular sclerosis–>leading to further decrease in nephron number
Describe 3 causes of injury to the renal vasculature
1) atherosclerosis of larger renal arteries
2) fibromuscular hyperplasia of one or more of large arteries which occludes vessels
3) nephrosclerosis-sclerotic lesions of smaller arteries, arterioles, and glomeruli
Describe atherosclerosis or hyperplastic lesions of large arteries
usually effect one kidney more than other, unilateral diminished kidney function, causes hypertension to kidneys
describe the most frequent form of kidney disease
benign nephrosclerosis/glomerulosclerosis-begins with leakage of plasma through the intimal membrane of the smaller interlobular arteries and in afferent arterioles, resulting in fibrinoid deposits to develop in medial layers of these vessels, followed by progressive thickening of the vessel walls which can constrict/occlude them-no collateral circulation among smaller renal arteries, occusion of one or more causes destruction of many nephrons, replacing kidney tissue with fibrosis
HTN, DM worsens
in healthy people how much does renal plasma flow and GFR decrease
40-50% by age 80
Describe chronic glomerulonephritis
slowly progressive disease leading to irreversible renal failure, may be following acute episode, or accompanied by SLE. Antibody/antigen complexes precipitated accumulate in glomerular membrane, causing inflammation, decreasing capillary tufts due to thickened glomerular membranes, healthy kidney tissue replaced by fibrosis which cannot filter fluid
Describe interstitial nephritis
results from vascular glomerular, or tubular damage that destroys nephrons, or it can result from damage to renal interstitum from bacteria, toxins, or drugs
bacterial=pyelonephritis (e.coli common culprit)-inability of bladder to empty, or obstruction of outflow
describe cystitis
proliferation of bacteria within the bladder resulting in inflammation within bladder
what is vasicoureteral reflux
urine going up ureter into kidney during urination due to failure of sphincter to close, can result in bacteria going up into renal pelvis
describe pyelonephritis-where does pyelonephritis usually effect in kidney
renal medulla, can spread to cortex, impairs ability of countercurrent multiplication and ability to concentrate urine. Pyelonephritis effects renal medulla interstitium, tubules, glomeruli, and other structures, may lead to CKD
Describe nephrotic syndrome 3 types
loss of large amounts of plasma proteins in urine because of increased glomerular permeability, can be due to chronic glomerularnephritis, amyloidosis (depositing of abnormal proteins or basement membrane of glomeruli 3)minimal change nephrotic syndrome
may be associated with CKD
in chronic kidney disease describe waste product accumulation in proportion to functioning nephrons
accumulation is proportional to number of functioning nephrons that have been destroyed, because urea and creatinine depend largely on glomerular filtration to be excreted, and they are not reabsorbed as readily as electrolytes
describe minimal change nephrotic syndrome
loss of negative charge in basement membrane of capillary can be due to antibodies, often occurs in kids b/t agens of 2 and 6-colloid osmotic pressure falls from 28-10 and plasma protein to less than 2
describe solutes phosphate, urea, and hydrogen in CKD
maintained near normal range until GFR falls below 20-30 percent of normal
this is maintained by decreasing tubular reabsorption of increasing tubular secretion
How are na and cl plasma concentrations maintained in CKD
decreasing tubular absorption of these electrolytes
with a 75% loss in functional nephrons, each surviving nephron must secrete 4 times as much na and 4 times as much volume
adaption from increased BF and increased GFR (hypertrophy of nephrons, dilation of blood vessels and glomeruli)
With decreased GFR how are normal rates of excretion accomplished?
normal rates of excretion can be maintained by decreasing rate of reabsorption of water and solutes by tubules
what is isosthenuria
inability of kidney to concentrate or dilute urine
why is concentrating ability of kidney impaired in isosthenuria
1) rapid flow of tubular fluid through collecting ducts prevents water reabsorption
2) rapid flow through LOH and CD prevents countercurrent mechanism, losing concentrating ability of medullary interstitium
name 2 factors that CKD has on body fluids
1) water and food intake
2) degree of impairment of renal function
describe clinical findings in uremia
generalized edema
acidosis
high concentrations of non-protein nitrogens (urea, creatinine, uric acid)
high concentration of phenols, sulfates, phosphates, K, and guanidine bases
why does fluid accumulation not occur until kidney function falls to 25% or lower
surviving nephrons excrete increased na and H2O, increased secretion of renin and angio II causing HTN
describe acidosis in kidney disease
Body produces 50-80 mmols of acid more than metabolic alkoli each day, and this accumulates in the renal patient over time. Buffers in body fluids can buffer 500-1000mmols of acid without lethal increases in ECF, and phosphate in bones can buffer an additional few thousand mmols of acid, but when these are depleted, pt pH can quickly become deadly acidic
Why do patients with renal disease develop anemia
erythropoeitin is produced in kidneys which stimulates bone marrow production of RBCs, with renal damage this is impaired
Describe Osteomalacia in CKD 2 reasons
1)bones partially reabsorbed and weakened
Vitamin D is converted by a two stage process in liver then to kidneys into 1,25-dihydroxychelecalciferol before it can promote calcium reabsorption from intestine. Damage to kidneys reduces blood concentration of active vitamin D, which decreases intestinal absorption
2)rise in serum phosphate due to decreased GFR, which increases binding of phosphate with calcium in plasma, decreasing ionized calcium which stimulates PTH secretion, causing secondary hyperparathyroidism, stimulates release of ca from bones
what type of renal lesions promote hypertension
those that reduce ability of kidneys to excrete na and water, ones that decrease GFR or increase tubular reabsorption
describe how increases in renal vascular resistance cause HTN
increases in vascular resistance reduces RBF and GFR (htn caused by renal artery stenosis)
describe how decreased glomerular capillary filtration coefficient reduces GFR
example-chronic glomerular nephritis causes inflammation and thickening of glomerular capillary membranes, thereby reducing glomerular capillary coefficient
describe how excessive tubular reabsorption of na causes HTN
example is HTN caused by excessive aldosterone secretion which increases na reabsorption in cortical collecting tubules
how can HTN be caused by patchy renal damage
if a part of kidney is damaged, renal tissue that is ischemic secretes renin which leads to angio II and increased BP (more na and water retention)
Describe pharmacological interventions to optimize kidney function in the face of HTN
block effects of nervous and hormonal signals (beta blockers, ARBs, ACE inhibitors)
vasodilate kidneys and increase GFR (ca channel blockers)
diuretics (directly inhibit renal tubular absorption of na and water)
describe renal glycosuria
failure of kidneys to reabsorb glucose
aminoaciduria
failure of kidneys to reabsorb Amino acids-essential cystinuria (renal calculi from failure to reabsorb), glycinuria (no absorption of glycine)
renal phosphatemia
failure to reabsorb phosphate, brittle bones refractory to vit D therapy
renal tubular acidosis
failure of kidneys to secrete H ions, so lots of HCO3 lost in urine, resulting in metabolic acidosis
nephrogenic diabetes insipidus
failure of kidneys to respond to ADH
fanconi’s syndrome
generalized reabsorptive syndrome of AA, gluc, phosphate, sometimes HCO3, increased secretion of K and calcium, usually effects PCT if caused by tubular injury
bartters syndrome
decreased na, cl and K reabsorption in LOH, due to impaired function of 1na, 2cl,1k transporter=hypokalemia, metabolic acidosis activates RAAS
gitelmans syndrome
decreased na cl reabsorption in DCT activates RAAS
Liddles syndrome
increased Na reabsorption, leading to HTN, metabolic alkalosis treated with amiloride
what does the rate of movement of solute across teh dialyzing membrane depend on
1) concentration gradient of the solute between the two solutions
2) permeability of the membrane to the solute
3) surface area of the membrane
4) length of the time that the blood and fluid remain in contact with the membrane
how much blood is in artifical kidney at one time
about 500 mL
total diffusion surface area is .6 to 2.5 square meters
what is bulk filtration
mass transfer of solutes and water can be produced by applying hydrostatic pressure to force the fluid and solutes across the membranes of the dialyzer
what does dialyzing fluid NOT contain
phosphate, urea, urate sulfate or creatinine, so they are readily absorbed into dialysate via concentration gradient
what is rate of clearance of urea from plasma in comparison to normal kidney
100-225ml/min compared to 70 ml/min
