Week 5 Renal Pathophysiology Flashcards
What percent do the kidneys receive of total cardiac output?
15-25%
How much is directed to renal cortex?
95%
How much is directed to medulla?
5%
How much blood flows through the renal arteries?
1-1.25L/min
What is more vulnerable to ischemic insults?
renal medullary papillae
what mean arterial pressures does the kidney successful autoregulate their blood flow?
60-160mmHg
What causes vasodilation and vasoconstriction of renal afferent arterioles and regulates the autoregulation of RBF?
intrinsic mechanism
innervation intact even in denervated kidneys
What is the purpose of the glomerulus?
separates the afferent arterioles from the efferent arterioles
What does the resistance in the efferent arterioles create?
hydrostatic pressure within the glomerulus to provide force for ultrafiltration
What are the capillaries lined with endothelial cells called?
podocytes
Glomerular filtration rate is
the rate at which blood is filtered through all of the glomeruli measure overall kidney function
SNS activation does what to renal blood flow?
reduces renal blood flow
Example of SNS activation and RBF:
shunt to skeletal muscle during exercise
surgical stimulation can increase vascular resistance
stimulates the adrenal medulla-> catecholamine release
if BP decreases SNS will also stimulate RASS
Antidiuretic hormone is released in response to
DECREASED stretch receptors in the atrial and arterial wall
Increased osmolality of the plasma (monitored by hypothalamus)
Where is ADH synthesized?
hypothalamus and is released from the posterior pituitary
what is the half life of ADH
16-24 minutes
What are the two primary functions of ADH
increases reabsorption of water in the kidneys
causes vasoconstriction and PVR to increase blood pressure
Perioperative causes of ADH release include:
hemorrhage positive pressure ventilation upright position nausea medications
Renin is
enzyme secreted by the kidneys that hydrolyzes angiotensin to angiotensin 1
Where is renin released?
juxtaglomerular cells located near the afferent arterioles
What is renin released in response to?
a decrease in arterial blood pressure
a decreased in sodium load delivered to the distal tubules
SNS beta 1 receptors
Angiotension 1 is converted to angiotension 2 where?
the lungs
Angiotensin 2 is
a potent vasoconstrictor and stimulates the hypothalamus to secrete ADH
Aldosterone is a
mineralocorticoid hormone release from the adrenal gland
What is the plasma half-life of aldosterone?
20 minutes
What does aldosterone do?
stimulates epithelial cells in the distal tubule and collecting ducts to reabsorb sodium and water
exchanges potassium to maintain electroneutrality
What does aldosterone the opposite of?
atrial natriuretic hormone function
Acute kidney injury is defined as
sudden inability of the kidneys to vary urine volume and content appropriately
Causes of AKI
pre-renal
intrinsic renal
post renal
Characteristics of AKI
develops rapidly but may resolve
has a 50% mortality rate
Spiralactone is what diuretic?
potassium sparing diuretic that blocks aldosterone receptors
Pre-renal is caused by
hemodynamic or endocrine factors that impair perfusion
hypoperfusion or hypovolemia
activates mechanism to conserve salt and water
can progress to permanent parenchymal damage
Examples of hypoperfusion or hypovolemia (pre-renal)
skin loss fluid loss hemorrhage sequestration vascular occlusion (thrombosis, aortic or renal artery clamping)
Renal or Acute Tubular Necrosis (ATN)
tissue damage from prolonged ischemia or nephrotic injury, glomerulonephritis
Patients with parenchymal disease will have trouble
concentrating urine
high urine sodium and low osmolality
Post-renal d/t
obstruction (calculi, blood clots, neoplasm)
surgical ligation
edema
Oliguric
<0.5ml/kg/hr
Polyuric
> 2.5L/day of non-concentrated urine
Risk factors for AKI/AKF
renal reserve decreases with age pre-existing renal dysfunction cardiac bypass, aortic aneurysms (supra-renal aortic clamping), ventricular dysfunctions sepsis use of nephrotoxic agents diabetes, HTN
Contrast Induced Nephropathy
results from administration of iodinated contrast media
transient and reversible form of acute renal failure
What is the treatment of CIN?
mainly supportive, consisting of careful fluid and electrolyte management although dialysis may be required in some cases
What is the suggested pathology of CIN?
direct toxicity of CM which could be related to harmful effects of free radicals and oxidative stress
while in renal tubules, excreted CM generates osmotic force causing marked increase in sodium and water excretion
diuresis will increase intratubular pressure which will reduce the GFR contributing to the pathogenesis of acute renal failure
Treatment of CIN
only supportive
prevention key
risk vs benefit should be considered
Oliguria is a sign of
inadequate systemic perfusion
What monitors can assess fluid status intraoperatively
urinary catheter TEE CVP blood pressure SVV
How do you treat oliguria?
assume prerenal oliguria is related to fluid until proved otherwise
selective dopamine DA1 receptor agonist can cause renal arteriolar vasodilation
-fenoldopam, low dose dopamine
What do you not give in the setting in intravascular hypovolemia?
diuretics
furosemide
mannitol
What population has a 1.5 greater risk of developing kidney failure?
hispanic americans
ESRD rates are how many time higher among African americans in comparison to whites?
4 fold
How many more times are native americans likely to be diagnosed with kidney failure?
1.8
What is the leading cause of kidney failure among american indians
diabetes
What is most prevalent among african american and major cause of ESRD in this population?
hypertension
what increased the risk of developing kidney disease and limit access to preventive measure and treatment in communities with socioeconomic and cultural differences?
language barriers education and literacy levels low income unemployment lack of adequate health insurance certain culture-specific health belieds and practices
Chronic renal failure is
slow progressive irreversible
decreased functioning nephrons
decreased RBF
decreased GFR, tubular function, and reabsorptive capacity
Common causes of chronic renal failure
glomerulonephritis pyelonephritis diabetes vascular or hypertensive insults congenital defects
Stages of Chronic renal failure
decreased renal reserve
renal insufficiency
end stage renal failure or uremia
Decreased renal reserve is asymptommatic until
<40% of normal nephron remain
Define renal insufficiency
10-40% of functioning nephrons remain
compensated, little renal reserve
Define end stage renal failure or uremia
> 95% of nephrons are nonfunctioning
GFR is <5-10% of normal
Severely compromised electrolyte, hematologic, and acid-base balances
Dialysis dependent
In ESRF, what is eventually lethal?
uremia
What are the six manifestations of chronic renal failure?
hypervolemia acidemia hyperkalemia cardiorespiratory dysfunction anemia bleeding disturbances
What are the three treatments of chronic kidney failure?
hemodialysis
peritoneal dialysis
kidney transplant
What are the four components of a urinalysis?
specific gravity
urine osmolality
proteinuria
urinary pH
Define specific gravity
measurement of solutes in the urine, indicates kidneys ability to excrete concentrated urine. It reflect tubular function
CHF, Liver Failure can lead to
hypovolemia, decreased CO and decreased effective circulating volume
NSAIDs, ACE inhibitors and cyclosporine can lead to
impaired kidney autoregulation
hypovolemia, decreased CO and decreased effective circulating volume and impaired kidney autoregulation can cause
pre-renal AKI
Two causes of Post- renal AKI are
bilateral uretotrophic obstruction
bladder outlet obstruction
ischemia, sepsis and nephrotoxins can lead to
acute glomerulophritis, tubular damage
Vascularitis, TTP/HUS and Malignant hypertension can lead to
vascular damage
vascular damage and acute glomerulophritis, tubular damage can lead to
Intrinsic renal AKI
GFR criteria and UOP criteria for renal failure risk
increased Cr x1.5 or GFR decrease <25%
UO <0.5ml/kg/hr x 6h
GFR criteria and UOP criteria for Renal Injury
Increased creatinine x2 or GFR decrease >50%
UO <0.5ml/kg/hr x 12 hrs
GFR criteria and UOP criteria for Renal failure
increased creatinine x3 or GFR decrease > 75% or creatinine >4mg/ 100ml (acute rise of >0.5mg per 100ml/dl)
OU <0.3ml/kg/hr x 24 hour or anuria x 12 hr
What does selective dopamine DA1 receptor agonist do?
causes renal arteriolar vasodilation
Fenoldopam
Low dose dopamine
3-10mcg of dopamine effects
increases contractility,
minimal change in HR and SVR
increase Renal BF
increase splanchnic BF
> 10 mcg dopamine effects
increase HR, vasoconstriction, decrease/increase renal BF, increase decrease splanchnic BF
> 10 mcg dopamine effects
increase HR, vasoconstriction, decrease/increase renal BF, increase decrease splanchnic BF
Three causes of pre-renal failure
absolute decrease in ECF volume
decreased RBF
altered intra-renal hemodynamics
Examples of absolute decrease in ECF volume for pre-renal failure
GI losses
hemorrhages
Examples of decreased RBF for pre-renal failure
heart failure
renal artery stenosis
Examples of altered intra-renal hemodynamics for pre-renal failure
Drug induced- NSAIDs/COX 2 inhibitors calcineurin inhibitors ACE inhibitors Angiotensin 2 receptor blockers sepsis hypercalcemia cirrhosis, Hepatorenal syndrome abdominal compartment syndrome
Two causes of intra-renal failure
tubulo-interstitial disorders
glomerular disorders
Types of tubulo-intestitial disorders for intra-renal failure
tubular injury (ischemic, nephrotic) Interstitial nephritis (allergic type or NSAID type)
Types of glomerular disorders for intra-renal failure
glomerulonephritis
thrombotic microanglopathies
atheroembolic disease
Two causes of post-renal failure
anatomic obstruction
tubular obstruction
Types of anatomic obstruction for post-renal failure
bladder outlet (prostate, pelvic tumor) ureteral (tumor, stones, strictures)
Types of tubular obstructution causing post-renal failure
crystals (Calcium oxalate
Drugs: indinavir, methotraxate
proteins (myeloma cast neuropathy)
Define urine osmolality
the number of moles per solute per kilogram of solvent
more specific than specific gravity
ability to excrete concentrated urine indicates good tubular function
Define proteinuria
when >150mg is excreted per day
when >750mg (3+ or 4+) is indicative of severe glomerular famage
failure of renal tubules to reabsorb protein
Define urinary pH
inability to excrete an an acid urine in the presence of acidosis is indicative of renal insufficiency
Glucose is freely filtered where?
the glomerulus
Where is glucose reabsorbed?
proximal tubule
Glycosuria is a sign
that the ability of the renal tubules to reabsorb glucose has been exceeded by an abnormally heavy glucose load
usual indicative of diabetes
What are the 4 laboratory tests for renal function
BUN
serum creatinine
Creatinine clearance
glomerular filtration rate
Define BUN
blood urea nitrogen
not a direct measure of renal function
influenced by exercise, steroids, and tissue breakdown
When is BUN elevated?
when kidney disease is reduced to about 75%
Define serum creatinine
muscle tissue turnover and dietary intake of protein
How is creatinine treated at the glomerulus?
freely filtered and neither reabsorbed or secreted
What is a good measure of GFR?
creatinine clearance
What is the best measure of glomerular function?
glomerular filtration rate
What is a normal GFR?
125ml/min
What is an symptomatic GFR?
<30-50% of normal GFR
What can be seen in an electrocardiogram in patients with renal disease?
peaked T waves
small or indiscernible P waves
What clinical situations contribute to increased K in renal failure patients?
LR Succinylcholine acidosis, electrolytes missed dialysis Vomiting diarrhea rhabomylasis
During blood storage what consistently leaks from cells?
potassium
How long are RBCs stored in blood bank?
42 days
How can potassium overload from transfusion be avoided?
using blood less then 5 days old
washing any unit of blood immediately before infusion to remove extracellular potassium
What does US describe in renal disease?
kidney size, hydronephrosis, vasculature, obstructions and masses
What does CT describe in renal disease?
detects stones of all kinds, masses may be evaluated using contrast
What does MRI describe in renal disease?
detailed tissue characterization, nice alternative to a contrast CT, reduced radiation exposure
What is gadolinium?
paramagnetic intravenous contrast agent
commonly used in MRA
What effects does GA have on renal function?
Pulse pressure variation and CO decrease
causing depression of renal BF, GFR, urinary flow and electrolyte secretion
What effect does regional anesthesia have on renal function?
parallels with degree of SNS blockade
decreased venous return
decrease in blood pressure
What are the peri-operative indirect effects of anesthesia on renal function?
circulatory and endocrine, SNS and patient positioning
What are the direct peri-operative effects of anesthesia on renal function?
medications that target renal cellular function
What is the effect of surgery on renal function?
stress and catecholamine release
fluid shifts
secretion of vasopressin and angiotensin
What are the three opioids effected by renal function?
morphine, meperidine, fentanyl
Why is morphine important in renal function?
active metabolite that depend on renal clearance mechanisms for elimination
principally metabolized by conjugation in the liver, and water soluble glucuronides (morphine 3 and morphine-6 glucoronide) are excreted via the kidney
Why is meperidine important to note with renal function?
active metabolite, normeperidine, depended on renal excretion
accumulation can lead to seizures and CNS toxicity
Why is fentanyl important to note with renal function?
not grossly altered by renal failure, but a decrease in plasma protein binding may result in higher free fractions
Ie decrease dose
Is ketamine dosing increased or decreased in CKD? Why?
not needed despite being metabolized in liver into active metabolite then metabolite being excreted in kidney
Name two gabapentinoids
gabapentin (neurtonin) and pregabalin (lyrica)
How are gabapentinoids effected in CKD?
liberal administration can increase risk of over sedation and coma
Agents do not undergo hepatic metabolism and are excreted solely by kidneys
reduction of 50% of the dose for each 50% decline in GFR or CCr and increasing time interval between dose recommended
What physiological renal responses occur with VA?
decrease in BP and kidneys increase renal vascular resistance causing decrease in renal blood flow
Isoflurane and renal physiological response
decrease BP in dose dependent fashion
Desflurane and renal physiological response
with increase HR, may maintain a greater degree of cardiac output and therefore renal perfusion
Sevoflurane and renal physiological response
free fluoride ion metabolite
compound A
When can compound A occur?
CO2 absorbents containing soda lime (KOH, NaOH, h20, CaOH2) degrade sevo resulting in production of vinyl ether
Risk of compound A exposure is dependent on (3)
duration of exposure
fresh gas flow rate
concentration of sevoflurane
Succinylcholine causes a rapid, transient increase in serum potassium by
0.5mEq/L
In patients with renal failure, succinylcholine can
be exaggerated to >0.5mEq/L
When is succinylcholine okay (with caution) to use in renal patient?
dialysis within 24 hours and normal serum K+
Non-depolarizing muscle relaxants and renal failure
the duration of action may be prolonged with renal failure
what two NDMRs are not effected by renal failure
cisatracurium and atracurium
How is sugammadex excreted?
the resultant sugammadex neuromuscular blocker complex by the kidney
What is an intermediate in the metabolism of sodium nitroprusside?
cyanide
What is the final metabolic product of sodium nitroprusside?
thiocyanate
Is the half life of thiocyanate prolonged in renal failure?
yes, normal 4 days but longer in CKF
Describe albumin role in kidney disease
may be protective by maintaining renal perfusion, binding of endogenous toxins and nephrotic drugs and preventing oxidative damage
What fluids can be associated with acute kidney injury and should be avoided?
hetastarch/ dextran
how hetastarch cause AKI?
breakdown of the synthetic carbohydrates to degradation products that cause direct tubular injury and plugging of tubules
What drugs can impair renal doses to dopamine?
anti-dopaminergics
metoclopramide, phenothiazines, droperiodol
Dopamine and fenoldopam
dilate afferent and efferent arterioles and increase renal perfusion
selective D1 agonist
What are the four renal pathophysiologies that require surgery?
renal cell carcinoma
renal dysplasia
polycystic kidney disease
wilm’s tumor
what is the most common renal malignancy?
renal cell carcinoma
Where does renal cell carcinoma originate?
proximal tubules
What is the cure to renal cell carcinoma?
surgical resection
refractory to chemo and radiation
What is the triad of renal cell carcinoma?
hematuria
flank pain
renal mass
When may CBP be needed for renal cell carcinoma?
when the tumor extens into the renal vein and the IVC and right atrium
What is renal dysplasia?
malformation of the tubules during fetal development
consists of irregular cysts of various sizes
how is renal dysplasia diagnosed?
in utero by US
Ureteropelvic junction and vesicoureteral reflux is also seen with
renal dysplasia
What does renal dysplasia lead to?
CKD, dialysis, transplant
Polycystic kidney disease is
an inherited massive enlargement of kidneys with compromised renal funciton
cyst can also occur on other organs (liver, pancreas, spleen)
non-functioning fluid filled cysts that range in size from small to mass effect producing size
How is polycystic kidney disease painful?
due to distention of cysts and stretching of fascia
What exacerbates PKD pain?
hemorrhage, rupture or infection
How does PKD progress into adulthood?
bilateral disease
Complications of PKD
HTN due to activation of RAAS
cyst infection
bleeding
decline in renal function
Treatment of PKD
symptom management
dialysis
transplant
How does wilm’s tumor present?
unilaterally and painless, palpable mass
what is wilm’s tumor associated with?
congenital/genetic malformations
Beckwith-wiedermann and WAGR
What is the most common malignant tumor in children?
wilm’s tumor
1/3 occur in age under 1
Where does wilm’s tumor metastasize?
lungs
treatment of wilm’s tumor includes?
resection and possible chemotherapy
capacity for rapid growth
Name the 5 stages of wilm’s tumor
stage 1: limited to kidney and completely excised
stage 2: tumor extends beyond the kidney but is completely excised
stage 3: inoperable primary tumor of lymph node metastasis
Stage 4: lymph node metasases outside the abdominal pelvic region
Stage 5: bilateral renal involvement
Total nephrectomy
renal artery and vein are ligated and then it involves removal of the kidney, the ipslateral adrenal gland, perinephric fat, and the surrounding tissue
partial nephrectomy
nephron sparing
considered with patients with solitary functional kidney, small leisons (< 4cm) or bilateral tumors, or for patients with increased risk because of other diseases such as diabetes or hypertension
Anesthetic requirements for nephrectomy
standard risk assessment identify smoking and age risk factors note any pre-existing renal dysfunction many are anemic (CBC and TC) K (BMP) regional anesthesia include blockade of nerve roots T8-L3 ERAS Opioid sparing
PTH increased Ca++ reabsorption exchanges
phosphate
Erythropoietin is
released by kidney in response to anemia, hypoxia
aldosterone is secreated from
adrenal cortex and causes reabsorption of Na
ADh/Vasopressin constricts
efferent arteriole and reabsorbs water
ANP
atrial distension (fluid overload) stimulates excretion of sodium and water
Dopamine is what receptor in renal vasculature and excretes?
Da1 receptor
sodium excretion
