Renal Review Flashcards
Major Functions of the Kidney
- Fluid and ion balance
- Removal of metabolic waste and chemicals from the circulation
- Gluconeogenesis
- Endocrine function and hormone secretion (renin, prostaglandins, kinins, erythropoietin creation, Vit D activation, etc)
Release of erythropoietin is stimulated by
low pO2 sensed in the renal interstitial causes specialized cells to release it (may be due to anemia, chronic hypoxia, or low RBF)
Why does kidney failure lead to osteoporosis
Lack of vitamin D activation leads to decreased absorption of calcium from the GI tract.
Kidney pain is sensed through these fibers
SNS fibers from T10-L1
SNS innervation to the kidneys is provided by these fibers and causes this
Supplied by pre-ganglionic fibers from T8-L1. These terminate on B1 receptors. NE release onto the B1 receptors results in release of renin.
Ultimately this results in increased angiotensin II creation and increase in BP. Thus, BBs have antihypertensive qualities through this link of decrease in angiotensin II creation.
PSNS innervation to the kidneys is from
The vagus nerve, which terminates on the ureters
Kidneys represent __% of body weight but receive __% of the CO
0.4% body weight
25% of CO
Which layer of the kidney receives the most blood flow?
The cortex (outer layer) receives more than the medulla (inner layer). Cortex = 85% RBF Medulla = 15% RBF
Only 6% of RBF goes to the medulla, despite it being very metabolically active at the thick ascending limb d/t all that active transport going on. Average O2 tension here is 8mmHg.
Describe cortical vs. juxtamedullary nephrons
Cortical
- Receive 85% RBF
- Found in the outer/middle cortex
- Have SHORT loops
- Efferent arterioles drain into peritubular capillaries
Jextumedullary
- Found in the inner renal cortex
- Long loops
- Efferrent arterioles drain into the vasa recta (concentration system / counter current mechanism –> vasa recta rectify the concentration gradient. Remember that long loops = better concentrating ability)
Describe the pathway of blood within the kidney
Renal artery - interlobar artery - arcuate - cortical radial - afferent arteriole - glomerular cappillaries - efferent arteriole - peritubular arteries or vasa recta (depending on nephron type) - venous system (cortical veins)
Percentage of blood that filters into the bowman’s capsule
25% gets filtered into the capsule.
The remaining 75% moves on to the efferent arteriole
What are mesangial cells?
Smooth muscle cells that surround BVs in the kidney and function to regular blood flow through the capillaries.
Filtration based on size in the gomerulus
3.6nm or >60-70kDa get excluded from the filtrate (Hgb and albumin) –> these are not filtered unless the glomerulus gets fucked up d/t glomerulonephritis
These tubules have a high amount of metabolic activity (active transport) and are at risk for ischemia
Proximal convoluted tubules and the thick ascending limb
Where does reabsorption of water take place?
Proximal tubules = 65% (no drugs target this area)
Loop of Henle = 15% (powerful diuretics like Lasix work here)
Distal tubules = 10%
Collecting ducts = 10%
Things that happen in the proximal convoluted tubule
- 65% of filtered Na, K, Cl, and H2O gets reabsorbed via the Na/K/ATP pump. The active movement of sodium is very important here, because it results in the movement of most other things with it.
- Almost 100% of glucose and amino acids are actively reabsorbed
- H+ ions are secreted into the tubule in exchange for bicarb
- Ca++ gets reabsorbed under the influence of parathyroid hormone
- Waste products get actively secreted into this tubule (bile salts, rate, creatinine, dopamine, and drugs)
- High peritubular pressure will result in less reabsorption
Things that happen at the loop of Henle
- Formation of hypertonic fluid via the counter current mechanism
- Descending loop -> tubule is permeable to water and it freely exits the tubule as the peritubular concentration increases
- TAL –> metabolically active. Na/K/Cl/Bicarb are all pumped out of the tubule. High O2 consumption in this area.
What is the JG apparatus?
The distal TAL/initial portion of the distal tubule meets with the macula dense and efferent and afferent arterioles
The macula dense is made of these two types of cells
Mesangial cells (SM cells that contract in response to angiotensin II and other vasoconstrictive substances to decrease GFR)
Granular cells.
- These secrete renin in response to
1) Direct B1 stimulation
2) Decreased RBF. Decreased stretch of the granular cells (renal baroreceptors) causes renin release. Also decreased Na and Cl concentration releases prostaglandins on juxtaglomerular cells, resulting in renin release.
Renin also stimulates the release of
ADH from the posterior pituitary and aldosterone from the adrenal medulla
Things that happen in the distal convoluted tubule
- Na/Cl/H2O are reabsorbed here under the influence of ADH and aldosterone
- H+ and K+ are secreted into the tubule here
- ADH = movement of aquaporins to increase H2O reabsorption
- Aldosterone = Na and water reabsorption and K secretion
Things that happen in the collecting duct
- Water is reabsorbed under the influence of ADH
- H+ may be secreted
- Principle Cells = Reabsorb Na and water in exchange for K (principle cells are principally a Na/K pump)
- Intercalated cells = Secrete H+ and reabsorb bicarb (H-ATP pump)
Overall, the late distal tubule and collecting duct play an important role in acid-base regulation.
ADH release from the posterior pituitary is stimulated
high Na concentration, high osmolarity, arterial/atrial baroreceptor activation, and by stimulation of angiotensin II.
__% of the glomerular filtrate is reabsorbed into the vascular system
99% gets reabsorbed.
Therefore, only 1% of the filtrate ends up becoming urine.
Things that happen in response to hypovolemia
- SNS activation and release of angiotensin II results in vasoconstriction and decreased GFR, and increased Na reabsorption
- Aldosterone = Increased Na absorption and K secretion
- Vasopressin (ADH) - increased H2O absorption in the collecting duct
Things that happen in response to hypervolemia
- ANP release (d/t stretch in the atria, results in vasodilation and increase in GFR)
- Decreased SNS and angio II release (results in more dilation and higher GFR, and less Na reabsorption)
- Increased capillary hydrostatic pressure discourages Na reabsorption
- Decreased aldosterone decreases Na reabsorption in the distal tubule and collecting duct
- Decreased vasopressin (ADH) = less water reabsorbed in the collecting duct
Main two mechanisms of how unwanted substances are removed from the body
1) Filtration –> gets filtered in the glomerulus and is not reabsorbed
2) Secretion –> gets directly secreted from the plasma, through the epithelial cells, and into the tubular fluid.
Urine is made mostly of filtered substances, and a few secreted substances
What is normal GFR?
125mL/min
What is the lower limit of auto regulation for the kidney?
MAP of 80-85.
Below this, RBF is pressure dependent. This is a higher limit than the brain!
GFR is considered a measure of ____
glomerular function
What are the major determinants of filtration pressure?
Glomerular capillary pressure (from tone of afferent and efferent arterioles) and glomerular oncotic pressure
Degree of SNS tone and RAAS stimulation effects on GFR
Mild to moderate SNS tone = mainly efferent tone, resulting in increased GFR
High SNS tone = mainly afferent tone, resulting in decreased GFR.
In SNS, you need all the fluid you can get to maintain BP and perfuse things! When you’re relaxed, that’s when you have the time to increase your GFR and make pee.
Why is it important for GFR to be regulated?
Too slow = too much reabsorbed, resulting in no urine output
Too fast = too fast to be effectively reabsorbed substances that our bodies need
Auto regulation of RBF is possible between these MAPs
80-200.
Modulation of GFR is done mainly though ___ tone
afferent
Mechanisms of renal autoregulation
1) Myogenic
- Inherent property of muscle that causes it to constrict in response to increased stretch. Relaxation occurs in response to decreased stretch.
2) Tuboglomerular feedback via the JG apparatus.
- THIS IS THE MAIN MECHANISM!!!!**
- Feedback is based on the amount of NaCl delivery to the macular densa from the distal TAL
- Too much NaCl delivery (from dehydration, HTN, or failed concentration mechanisms in ARF) results in the release of renin and adenosine, resulting in afferent constriction.
- Too little NaCl delivery (d/t hypotension) means that catecholamine and renin levels are low, resulting in afferent dilation and efferent constriction to increase GFR
Importance of prostaglandins
- Protect against renal ischemia
- Produced by the actions of phospholipase A2 and COX
- Prostaglandins are released by the kidneys in response to renal ischemia, renal hypotension, and physiologic stress.
- Prostaglandins increased urine output and oppose the actions of angiotensin II, SNS stimulation, and ADH, which all try to decrease RBF.
What common anesthesia drug should be avoided because it blocks prostaglandin production and puts the kidneys at risk for ischemia?
TORODOL!
It’s an NSAID, and thus a COX inhibitor.
Note that NSAIDs are only nephrotoxic in the ischemic kidney, not to the normal kidney. NSAIDs like Toradol are bad for renal patients because they are usually dependent on their renal prostaglandins to maintain flow
What does ANP do?
- Gets released in response to atrial stretch (hypervolemia)
- Blocks the reabsorption of Na in the distal tubule and collecting duct (resulting in natriuresis!)
- Results in an overall increase in GFR d/t natriuresis, decreased renin release, and causes systemic vasodilation (overall reducing BP).
What does nitric oxide do?
- Opposes the vasoconstrictive effects of the SNS and RAAS
- Promotes excretion of Na and H2O
- Influences tubuloglomerular feedback
- No drugs target the effect on NO on the kidneys
Low dose dopamine
1-2mcg/kg/min
Does increase GFR and UO, but does not decrease the incidence of ARF, dialysis, or mortality.
BUT, remember that it’s very hard to control dopamine levels in the body, so even if you’re giving low doses, sometimes people will still end up in the alpha range of dopamine concentrations, which promotes renal vasoconstriction.
Renal auto regulation can be severely reduced in these cases:
- Sepsis
- ARF
- CPB
In these cases, vasoconstrictors may be necessary to restore normal renal perfusion pressures.
Medications that may offer renal protection
Fenoldopam
- DA1 agonist (has NO DA2 or alpha activity), MAY help preserve post-op renal dysfunction in high risk patients. Several small studies are promising, but larger studies have conflicting results)
PGE-1
- Synthetic prostaglandin that may be protective against ischemia –> benefit still being investigated
CCBs
- Pros –> Can reduce reflow vasoconstriction and Ca influx after ischemic injury, inhibits angiotensin, reduces free O2 radicals, and is protective in the presence of certain nephrotoxins like contrast, cyclosporin, and cisplatin. Remember that high intracellular Ca is a signal for apoptosis, so it is protective in this regard.
- Cons –> May reduce BP and disrupt renal auto regulation
NE
- Used in auto regulation dysfunction in septic shock. Can be renal protective if it increases MAP > 60, therefore increasing GFR and UO.
Arginine Vasopressin
- Increases renal perfusion pressure and preferentially constricts the efferent arteriole.
- Septic patients have reduced levels of AVP, so they benefit from low doses of it. This therapy may be beneficial in certain sub-categories of patients.
Effects of spinals and epidurals on renal function
- Sympathectomy from T4-10 will cause a decrease in release of catecholamines, renin, and vasopressin. This is good for maintaining RBF.
This is the most critical factor in maintaining renal perfusion pressure
Proper fluid balance
General effect of most anesthetic agents on renal function
- Usually they decrease GFR and UO. These changes usually reverse after emergence. This is usually d/t VC depression (more prevalent with iso than high opioid technique)
- Pre-hydration and attenuation of the stress response is protective against ischemia
- Renal autoregulation and hormone function is usually intact.
- The physiologic stressors of surgery usually have more of an impact than the anesthesia (CPB, hypovolemia, and aortic cross clamping)
Usually deleterious changes in renal function are transient, unless the pt had decreased renal function in the first place.
This anesthetic agent can help preserve RBF during hemorrhagic hypovolemia despite the fact that it does decrease UO
Ketamine
What is the concern with VAs and renal function?
Main concern is the production of free fluoride ions that result in tubular injury and decreased ability to concentrate urine.
Sevo and fluoride levels
Fluoride levels may rise close to levels associate with risk, but clinical evidence of injury does not exist.
PPV and renal function
The higher the PIPs and PEEP results in a decrease in RBF, GFR, and UO.
This is due to a decrease in preload and CO. This also results in SNS activation, RAAS, and release of vasopressin.
Hydration can help overcome these changes
Common causes of CRF
1 = DM
CRF is caused by a decrease in the number of functioning nephrons, caused by:
#2 = HTN
- Chronic glomerulonephritis
- Traumatic loss of kidney tissue
- Congenital absence of kidney tissue
- Polycystic kidney disease (cysts destroy the nephrons)
- Urinary tract obstruction, like stones (causes back-up and high pressure system that destroy nephrons)
- Pyelonephritis (infection of the renal pelvis)
- Diseases of the renal vasculature
CRF is diagnosed with a GFR
25mL/min
Normal is 90-125mL/min
These are the reasons for continued deterioration of renal function in diabetics and hypertensive patients
Glomerular HTN, hyperfiltration, and glomerulosclerosis.
These are the only drugs proven to slow the progression of renal dysfunction
ACE-Is and ARBs
You can have normal renal function with only __% of normal functioning nephrons
30%
Below this, you start seeing problems
Why may you see an increase in UO as kidneys start to fail?
Large quantities of urea, phosphates, sulfates, uric acid, and creatinine accumulate in the ECF. Only a small portion of this shit reabsorbed, so they act as an osmotic diuretic within the tubules.
Long term dialysis is required when Cr > ___ or when GFR
Cr > 3
GFR
Physiologic effects of CRF
- Excess fluid results in generalized edema
- Accumulation of nitrogenous waste products like creatinine and uric acid
- High concentrations of phenols, sulfates, phosphates, and K+
- Osteomalacia (kidneys not activating Vit D –> results in low calcium levels and hyperparathyroidism). Calcium also low d/t accumulation of phosphates.
- Pruritis (itchy skin d/t histamine release –> probs from all that shit building up in the body)
Anemia in CRF
- Hgb may be as low as 5-8g/dL d/t decreased production of erythropoietin
- EPO therapy is useful in this population, however, it can cause HTN and worsens existing HTN
H/H goals for CRF patients
Hgb > 12g/dL in females and >13g/dL
Hct 36-40%
How do renal patients compensate for their anemia?
Increase production of 2,3-DPG
Why do we want to avoid blood transfusions in CRF patients?
To avoid exposure to HLA antigens, which can decrease the potential success of a future transplant.
Coagulopathies in CRF
- You will see an increase bleeding time despite a normal PT, PTT, INR, and platelet count
- This is mostly due to release of defective von Willebrand factor
- This places patients at risk for GI bleeds, hemorrhagic pericarditis, and SDH
How can coagulopathies be treated in CRF patients?
Desmopressin (DDAVP)
- Onset
Altered electrolyte balances in CRF
- Unpredictable intravascular fluid volume
- Hyperkalemia (peaked T waves, prolonged PR and QRS, heart blocks, and V-fib)
- Hypocalcemia secondary to hyperphosphatemia
- Hypermagnesemia (can cause CNS depression and coma)
- Metabolic acidosis (d/t inability to excrete H+ ions)
Treatment for hyperkalemia
Insulin 10 units + amp D50
Reason for HTN in CRF
- Increased intravascular volume and activation of the RAAS
- -> Places the pt at risk for CHF, MI, and stroke
Treatment for HTN in CRF patients
1) ACE-Is and ARBs are first line drugs!!
2) BBs (cardioprotective)
3) CCBs
Therapy is aimed at BP
Uremic pericarditis, which is associated with CRF, can lead to
Tamponade and necessitate a pericardial window
CRF and the nervous system
- Uremic neuropathies
- Uremic encephalopathy (can range from mild irritability to coma)
- Distal symmetric mixed motor and sensory polyneuropathies (median and common perennial nerves affected most frequently)
- In ESRD, may begin to see paresthesias, hyperesthesias in feet, and BLE weakness
Infection and CRF
- Most common cause of death!!!***
- Usually d/t pulmonary infection
- Associated with uremia
- Important to utilize aseptic technique!!
Of the pts on dialysis who die, half is from infections, and the other half is from CV disease
What is ARF?
A sudden deterioration in renal function with no time to compensate!
Defined as an increase in Cr by 0.5 or a decrease in Cr clearance by 50%
May be oliguric (400mL/day)
3 Categories of ARF
Pre-renal
- Decreased blood supply to kidneys from CHF, low CO/BP, low circulating blood volume – shock syndromes
Intra-renal
- D/t some abnormality WITHIN the kidney
- Destruction of tubular epithelial cells. Cells slough off, and block nephrons, leading to no urine output. This is also called acute tubular necrosis.
Post-Renal
- Obstruction somewhere within the collecting system (blood clot, bladder obstruction, urethral obstruction)
Why is the mortality rate so high in ARF?
Because there is no time for the body to compensate! The body isn’t used to high K+ or severe anemia. Mortality is >50% once the pt needs dialysis, of if they develop MODS, resp failure, or hypotension.
Remember that the cells in the TAL are the most vulnerable to ischemia d/t high metabolic demand. Damage is reversible if RBF remains within 20% of baseline.
As long as the basement membrane remains intact, new epithelial cells can form in 10-20 days.
Patients who are at risk for ARF following anesthesia
- Those with pre-op renal insufficiency****
- Those with CHF or CAD
- Cardiac events that occur per-op (causes inadequate BP and CO)
- Sepsis, emergency surgery, or trauma
- The elderly
- ESLD
- Hypovolemia
- Nephrotoxic exposure (NSAIDs, antibiotics, chemo, immunosuppressants, contrast, etc)
- CPB
- Aortic clamping
- Liver or kidney transplant procedures
- Nephrectomies
The most important factor to prevent ARF in these patients is to maintain normovolemia through the use of invasive monitoring!!
Physiologic effects of ARF
Overall, retention of water, electrolytes, and waste products
- HTN, CHF, and pulm edema
- Hemodilution (Hct may only be 20-30%)
- GI bleeds
- Hyperkalemia
- Metabolic acidosis
- Neurologic damage (uremic encephalopathy)
- Uremia induced immune suppression (infection risk)
Management of the patient in ARF and prevention of ARF in high risk patients
Will only present to the OR if it is EMERGENCY surgery
- Want to keep MAP > 65, and probably higher than that
- Fluid resuscitation (no benefit of crystalloids vs colloids, but hetastarch may be harmful)
- Mannitol - may be used in renal transplants
- N-acetylcysteine may be protective in high risk patients getting contrast dyes
- Activated Protein C and Steroid Replacements - may also help prevent ARF in high risk patients. Steroids are for those already on steroid therapy.
- Vasopressors- may be needed to support BP because renal auto regulation is lost.
Drug dosing in renal failure
- Reduce the dose of drugs cleared unchanged by the kidneys once GFR
Drugs and protein binding in renal failure
Acidic drugs will bind to protein less
Basic drugs will bind to protein more
Thus, be careful with acidic drugs, because they bind to protein less and can result in dangerously high drug levels.
Common drugs like ________ are at least partially cleared by kidneys, so it’s best to use alternatives if possible in this population
PCN, cephalosporins, pancuronium, vecuronium, barbiturates, neostigmine, glyco, atropine, hydralazine, morphine, and meperidine.
TPL consideration
Normally highly protein bound, free fraction may be 2x normal.
Considerations for propofol, ketamine, and etomidate
No clinical changes need to be made in dosing. Maybe decrease because those in renal failures are more sensitive to them.
Considerations for versed
60-80% cleared by the kidneys as an active metabolite. Benzos are also highly protein bound, so you may see a profound or prolonged clinical effect. Either skip this med or give a decreased dose.
Considerations for Precedex
Highly protein bound, and will see prolonged sedation. Also the drop in BP may not be good for these patients.
Opioids in renal failure
- Morphine - avoid d/t active morphine-6-glucuronide
- Meperidine - avoid d/t normeperidine
- Dilaudid - Avoid repeat dosing d/t hydromorphone-3-glucuronide
- Fentanyl - GOOD CHOICE!
- Alfentanil - Ok, but be careful if giving a loading dose d/t decreased protein binding. No major prolongation of clinical effect.
- Remifentanil - Good choice as well. There is a minimally active metabolite, remifentanil acid, but no major clinical implications.
- Codeine - Potential for prolonged narcosis. Not recommended for long-term use.
Avoid these muscle relaxants in renal failure
d-tubocurarine
Gallamine
Metocurine
Pancuronium
Roc and vec in renal failure
Single dose ok, but may have prolonged prolonged effect with repeat dosing. Also, vet has an active metabolite.
Sux in renal failure
Single dose ok, but check K+ first. Don’t even think about using a drip, you fucking asshole. Active metabolite = succinylmonocholine.
The increase in K+ is well tolerated in most pts with ESRD because they are used to living with high K+ values.
Normal dosing can be used for these MRs
Atracurium, cis-atracurium, and mivacurium
These tests are measures of GFR
BUN 10-20
Creatinine 0.6-1.5
Creatinin Clearance 110-150
GFR is the best reflection of renal function because it parallels nephron function, and creatinine clearance is the best indicator of GFR.
BUN depends on urea production, amount of protein in the diet, GI bleeds, and dehydration
Creatinine depends on muscle mass. High Cr in the elderly should be concerning because they have lower muscle mass.
These tests are measures of renal tubular function
Urine spec grav = 1.003-1.030
Urine osmolarity = 38-1400
Creatinine clearance
An increase in plasma creatinine won’t occur until __-__ hours after a decrease in GFR
8-17 hours
A BUN > ____ is indicative of decreased GFR
50
An AV fistula is usually composed of these two vessels
Cephalic vein and radial artery
Emergency dialysis is usually accessed through
Jugular vein or femoral vein
Dialysis patients have a ___% annual mortality rate
25%
Side effects of dialysis
- Hypotension
- Hypersensitivity (ethylene oxide or polyacrylonitrile)
- Hypokalemia - remember that most K is intracellular, so it will take a while for K+ to equilibrate out of the cells
- Anemia
- Infection
- Cramps, HA, N/V
