Renal Pathophysiology Flashcards
Kidneys receive ___% total CO
15-25%
95% directed to the renal cortex (glomerulus)
5% to the medulla
Renal Autoregulation
INTRINSIC - intact even in denervated kidneys
Tubuloglomerular feedback
Renal Blood Flow
Afferent arteriole → glomerular capillary → Bowman’s capsule → proximal tubule → loop of Henle descending → ascending → macula densa → distal tube collecting duct
Glomerulus
Separates the afferent from efferent arterioles
Resistance in efferent arterioles creates hydrostatic pressure w/in glomerulus
Capillaries lined w/ podocytes
GFR
Glomerular filtration rate
Rate blood filtered through all glomeruli
Measures overall kidney function
SNS Activation
↓RBF
Blood shunted to skeletal muscle during exercise
Surgical stimulation ↑vascular resistance
Stimulates adrenal medulla → catecholamine release
↓BP → RAAS activation
ADH
Vasopressin
Antidiuretic hormone Released in response to ↓stretch receptors in atrial/arterial wall & ↑plasma osmolality Synthesized in hypothalamus Released from posterior pituitary Half-life 16-24 minutes Constrict efferent arteriole H2O reabsorption
ADH Primary Functions
- ↑renal H2O reabsorption (osmolality)
2. Vasoconstriction ↑SVR ↑BP
Periop Release ADH Causes
Hemorrhage PPV + Upright position Nausea Medications
Renin
Enzyme secreted by kidneys Hydrolyzes angiotensin → angiotensin I Released from JG cells near afferent arterioles - ↓arterial BP - ↓Na+ load delivered to distal tubules - SNS β1 receptors
Angiotensin
Angiotensin I converted in the lungs by ACE into angiotensin II
Angiotensin II potent vasoconstrictor & stimulates hypothalamus to secrete ADH
Aldosterone
Mineralocorticoid hormone released from the adrenal gland
Plasma half-life 20 minutes
Stimulates epithelial cells in distal tubule & collecting ducts to reabsorb Na+ & H2O (exchanges K+ to maintain electroneutrality)
Spironolactone
K+ sparing diuretic that blocks the aldosterone receptors
Acute Renal Failure
AKI
Sudden inability to produce urine
Develops rapidly but may resolve
50% mortality rate
Pre-Renal
Hemodynamic or endocrine factors impair perfusion
Causes - hypotension, shock, hypovolemia, hemorrhage, burns (fluid shift), vascular occlusion (thrombosis or clamping), ↓RBF (heart failure or renal artery stenosis), hepato-renal syndrome
Activate RAAS → ADH
Low urine Na+ ↑osmolality
Possible to progress to permanent parenchymal damage
Intra-Renal
Acute Tubular Necrosis
Direct kidney tissue damage
Causes - inflammation/infection, reduced blood supply, prolonged ischemia, nephrotic injury (antibiotics, chemo, contrast dye), glomerulonephritis
Parenchymal disease difficult to concentrate urine
↑urine Na+ ↓osmolality
Post-Renal
Urinary outflow obstruction
Causes - kidney stones (calculi), stricture, blood clots, neoplasm, bladder/pelvic tumor, prostate enlargement, or injury
Less common in OR setting
Anuria
<100mL/day
Oliguria
<400mL/day
<0.5mL/kg/hr
OR oliguria indicates inadequate systemic perfusion
Polyuria
> 2.5L/day
Non-concentrated urine
Acute Renal Failure
AKI Risk Factors
↓renal reserve w/ age
Each year after 50 creatinine clearance ↓1.5mL & renal plasma flow ↓8mL
Pre-existing renal dysfunction
Surgical procedures
- Cardiac bypass >2 hours
- Aortic aneurysms (supra-renal aortic clamping)
- Ventricular dysfunctions
Sepsis - hypovolemia, hemolysis, DIC, infections, acidosis
Nephrotoxic agents
Diabetes
Hypertension
AKI Prevention
Prevention renal insult more successful than management
Hydration
Maintain blood pressure
Euvolemia
Contrast-Induced Nephropathy
3rd most common cause hospital acquired AKI
Results from iodinated contrast media admin
Transient & reversible acute renal failure
1° supportive treatment
- Fluid & electrolyte management
- Dialysis
Low incidence in normal renal function patients 0-5%
Pre-existing renal impairment 12-27%
Diabetic neuropathy up to 50%
CIN Risk Factors
Pre-existing renal disease Diabetes Hypertension Volume-status (dehydration) Obesity Hepato-renal injury
CIN Pathology
Unclear
Hypoxia & hypo-perfusion exacerbate injury
Direct contrast media toxicity r/t harmful effects free radicals & oxidative stress
Excreted contrast in renal tubules generates osmotic force causing ↑Na+/H2O excretion
Diuresis ↑intratubular pressure ↓GFR → acute renal failure
CIN Treatment
Supportive
Prevention = key
Contrast media diagnostic studies or interventional procedures weigh risk against benefit
Intraop Monitors
Rapid recognition & treatment to prevent renal insult Foley Transesophageal echocardiogram CVP (less accurate) Blood pressure Stroke volume variation
Oliguria Treatment
Assume pre-renal oliguria r/t fluid until proven otherwise
Blood
Selective dopamine receptor agonists cause renal arteriolar vasodilation - Fenoldopam & low-dose dopamine <3mcg/kg
Diuretics - Furosemide or Mannitol (do not admin in patient w/ intravascular hypovolemia)
Chronic Renal Failure
Slow, progressive, & irreversible
↓nephron function ↓RBF ↓GFR
Causes - glomerulonephritis, pyelonephritis, diabetes, vascular or hypertensive insults, or congenital defects
Renal Insufficiency
↓renal reserve asymptomatic until <40% normal nephron remain
Insufficiency when 10-40% functioning nephrons remain
Compensated w/ minimal renal reserve
ESRD
End-stage renal disease/failure
>95% nephrons non-functioning
GFR <5-10% normal
Severely compromised electrolyte, hematologic, & acid-base balance
Uremia - urine in the blood eventually lethal
Dialysis dependent
Chronic Renal Failure S/S
Hypervolemia Acidemia Hyperkalemia Cardiorespiratory dysfunction Anemia Bleeding disturbances
Chronic Renal Failure Treatment
Hemodialysis HD
Peritoneal dialysis PD
Kidney transplant
Urine Specific Gravity
Measure solutes present in urine
Indicates kidneys ability to excrete concentrated urine
Reflects tubular function
Urine Osmolality
Number moles solute per kilogram solvent
More specific than specific gravity
Ability to excrete concentrated urine indicates adequate tubular function
Proteinuria
> 150mg excreted per day
750mg (3+ or 4+) indicates severe glomerular damage
Failure renal tubules to reabsorb protein
Urinary pH
Inability to excrete an acid urine in presence acidosis
Indicates renal insufficiency
Glucose
Freely filtered at glomerulus
Reabsorbed in proximal tubule
Glycosuria indicates renal tubules ability to reabsorb glucose exceeded by abnormally heavy glucose load
Indicates diabetes mellitus
BUN
Blood urea nitrogen
Not direct renal function
Influenced by exercise, bleeding, steroids, & tissue breakdown
Elevated in kidney disease when GFR reduced to 75%
Serum Creatinine
Muscle tissue turnover & dietary protein intake
Creatinine freely filtered at glomerulus & neither reabsorbed nor secreted
Creatinine clearance measures GFR
↑Creatinine
Ketoacidosis
Cephalothin/Cefoxitin
Flucytosin
Other drugs - ASA, cimetidine, probenecid, trimethoprim (inhibit tubular creatinine secretion)
↓Creatinine
Advanced age (elderly) physiologic ↓muscle mass
Cachexia pathologic ↓muscle mass
Liver disease ↓hepatic creatinine synthesis
GFR
Glomerular filtration rate
Best measure glomerular function
Normal 125mL/min
ASYMPTOMATIC until GFR decreases to <30-50% normal
Hyperkalemia
Peaked T waves
Small or indiscernible P waves
PRBCs
Blood storage → constant potassium leak
Potassium ↑0.5-1mmol/L per day refrigerator storage
Blood stored in blood bank up to 42 days
Minimize Transfusion Hyperkalemia Risk
Select blood collected <5 days prior to transfusion
Wash blood immediately before infusion to remove extracellular potassium
K+ absorption filters during transfusion to decrease K+ loading
Rate & volume contribute to K+ levels as well as patient pre-transfusion circulating blood volume
General Anesthesia
PPV ↓CO
↓RBF, GFR, urinary flow, & electrolyte secretion
Regional Anesthesia
Parallels w/ SNS blockade degree
↓VR ↓BP
Direct & Indirect Effects
Direct: - Medications that target renal cellular function Indirect: - Circulatory - Endocrine - SNS - Patient positioning
Surgery Impact on Renal Disease
Stress & catecholamine release
Fluid shifts
Vasopressin & angiotensin secretion
Opioids
Morphine - active metabolites depend on renal clearance
Meperidine - normeperidine active metabolite
Fentanyl ↓plasma protein binding ↑free fraction available
CKD ↓opioid dosages
Ketamine
Hepatic metabolism
Norketamine metabolite hydroxylated into water-soluble
Renal excretion
Gabapentinoids
Gabapentin (Neurontin) & Pregabalin (Lyrica)
Solely renal excretion
↓dose 50% each 50% ↓GFR
↑time interval b/w doses
Inhalational Agents
Hypotension → compensatory ↑renal vascular resistance ↓RBF
Isoflurane ↓BP (dose-dependent)
Desflurane ↓BP ↑HR maintain CO & renal perfusion
Sevoflurane - free fluoride ion metabolite
Compound A
CO2 absorbents containing soda lime (KOH, NaOH, H2O, CA(OH)2) degrade Sevoflurane resulting in production vinyl ether
Higher risk w/ closed-circuit anesthesia
Dependent on duration exposure, FGF, & concentration
Propofol
Does not adversely affect renal tubular function
Prolonged infusion → green urine d/t presence phenolic metabolites
Discoloration does not affect renal function
PRIS - renal failure 2° rhabdomyolysis, myoglobinuria, hypotension, metabolic acidosis
Succinylcholine
Careful admin
Rapid transient ↑K+0.5mEq/L
Metabolism pseudocholinesterase → succinic acid & choline
Metabolic precursor succinylmonocholine renal excretion
Preop & postop dialysis w/in 24 hours
NDMRs
Prolonged elimination 1/2 life
Vecuronium 0.9 → 1.4hr 30% renal excretion
Atracurium 0.3 → 0.4hr (Hoffman elimination)
Pancuronium 1.7 → 8.2hr
Rocuronium 0.7 → 1hr
Mivacurium 0.03 → 0.06hr
Sugammadex
Cyclodextrin molecules inactivate aminosteroidal NMBs
Renal excretion
Cyclodextrin complexes accumulate in severe renal impairment
Insufficient data concerning long-term exposure
Sodium Nitroprusside
Nitroprusside → cyanide → thiocyanate
Thiocyanate 1/2 life >4 days (prolonged in renal failure)
Thiocyanate Toxicity
Levels >10mg/100mL
Associated w/ long-term infusions >6 days
Hypoxia, nausea, tinnitus, muscle spasm, disorientation, & psychosis
Albumin
Protective
Maintains renal perfusion, binds endogenous toxins, nephrotoxic drugs, & prevents oxidative damage
Hetastarch/Dextran
Associated w/ AKI 2° breakdown synthetic carbohydrates to degradation products that cause direct tubular injury & tubules plugging
Worsened w/ ↓renal perfusion
Dopaminergics
Fenoldopam selective D1 agonist
Low-dose dopamine
Dilate afferent & efferent arterioles
↑renal perfusion
Anti-Dopaminergics
Metoclopramide, Droperidol, & phenothiazines
Impair renal response to dopamine
Renal Cell Carcinoma
Most common renal malignancy 80% all solid renal masses Originates in proximal tubules lining Refractory to chemotherapy or radiation Classic triad presentation Surgical resection often curative
Classic Triad Presentation
Hematuria
Flank pain
Renal mass
Renal Dysplasia
Renal tubules malformation during fetal development
Irregular cysts
Utero diagnosis via ultrasound
Bilateral incompatible w/ survival
90% patients have contralateral hypertrophy as adults (healthy kidney compensation)
→ CKD, dialysis, transplant
Polycystic Kidney Disease
Inherited (dominant or recessive) renal enlargement w/ compromised function
Non-functioning fluid filled cysts microscopic to mass-effect size
Cysts present on other organs (liver, pancreas, spleen)
Painful d/t cyst distension & fascia stretching
- Hemorrhage, rupture, or infection exacerbate pain
PKD Complications
HTN d/t RAAS activation
Cyst infections
Bleeding
Decline in renal function
PKD Treatment
Symptom management
Dialysis
Transplant
Wilm’s Tumor
Nephroblastoma
Unilateral painless, palpable abdominal mass
Associated w/ congenital/genetic malformations
Most common pediatric malignant renal tumor
1/3 occur under 1yo
Resection & possible chemo
RAPID growth
Metastasis → lungs
Wilm’s Tumor
Stage 1
43%
Limited to kidney
Completely excised
Wilm’s Tumor
Stage 2
23%
Tumor extends beyond kidney but completely excised
Wilm’s Tumor
Stage 3
20%
Inoperable primary tumor or lymph node metastasis
Wilm’s Tumor
Stage 4
Lymph node metastases outside abdominopelvic region
Wilm’s Tumor
Stage 5
Bilateral renal involvement
Total Nephrectomy
Renal artery & vein ligated
Remove kidney, ipsilateral adrenal gland, perinephric fat, & surrounding fascia
Other kidney needs to be functional
Partial Nephrectomy
Nephron sparing surgery
Patients w/ solitary functional kidney, small lesions <4cm, or bilateral tumors
↑risk patients d/t other comorbidities diabetes or HTN
Open, laparoscopic, and/or robotic
Nephrectomy
Anesthetic Considerations
Type + cross CBC & electrolytes Regional anesthesia nerve roots T8-L3 ERAS Opioid sparing
Parathyroid Hormone
↑Ca2+ reabsorption
Exchange phosphate
Erythropoietin
Released from kidney in response to anemia or hypoxemia
ANP
Atrial natriuretic peptide
Fluid overload → atrial distension
Stimulates Na+ & H2O excretion
Dopamine
DA1 receptor
Located in renal vasculature
Vasodilation & Na+ excretion
Nephrons
Each kidney has 1 million nephrons
2 kidney nephrons end-to-end 10 miles
Kidneys filter blood _____ times per day
20-25x per day
Renal Agenesis
Born w/ one kidney or kidney removed
Body only loses 25% kidney function d/t hypertrophy to sustain the body
