Miscelaneous Wisdom

Question 0

When deciding whether to anticoagulate someone on A-fib, what is the most important consideration?

Answer 0

Evaluating the tradeoff between the risk of stroke vs. the risk of major bleeding.

The risk of stroke can be assessed with the CHADS2 risk score, the CHA2DS-VASc score, and the ATRIA score.

The risk of major bleeding can be assessed using the HAS BLED score. Also, whether or not the patient might need to go to surgery.

Question 1

When you have a patient on A-fib, which two management priorities must you consider?

Answer 1

0. Electric/medical cardioversion
1. Rate control or rhythm control
2. Anticoagulation for thromboembolism/stroke prophylaxis

Question 2

When should you use CHA2DS2-VASc as oppose to CHADS2?

Answer 2

When the CHADS2 score is 0, so as to further stratify the risk of people who are considered low risk on CHADS2.

CHA2DS2-VASc uses all of the criteria in CHADS2, but also stratifies patients in to 3 age groups with different point weights, and uses hx of other vascular disease and gender (female) as criteria.

Question 3

Which form of afib control confers lower risk of tromboembolism, rate- or rhythm-control?

Answer 3

NEITHER! The risk is the same.

Question 4

How is the ATRIA risk score for evaluating anticoagulation for afib different from CHADS2, CHA2DS2-VASc?

Answer 4

It divides patients into 4 age categories, and has a separate set of point values for age groups based on whether the patient has or has not had a prior stroke/TIA.

Like CHA2DS2-VASc, includes gender and vascular disease (?) as factors. Also, ATRIA is one of the only risk scoring systems that includes factors related to CKD, which has been found to be correlated with risk of thromboembolism in afib (although mech not quite clear).

Question 5

What is the mechanism of thrombus formation in afib?

Answer 5

Think of Virchow’s triad:

• Stasis: the irregularly irregular contraction of the atria (not concerted) leads to areas of decreased flow (has been confirmed using echo/doppler), particularly in the left atrial appendage(LAA).
• Endothelial abnormalities/damage: the shape and nature of atrial endothelium of patients with afib may be abnormal, which may contribute to thrombus formation.
• Hypercoagulability: it has been suggested that afib confers a transient hypercoagulable state. Moreover, it has also been suggested that cardioversion (electric v. medical?) might cause a hypercoagulable state.

Bottom line, the mechanism is not 100% nailed down, but we know that it is related to multiple, interacting factors.

Question 6

What is azotemia?

HINT: sounds nothing like what it represents. Go figure.

Answer 6

It means elevation of BUN + creatinine that characterizes kidney failure.

Question 7

When do you see an elevated BUN for reasons OTHER than for kidney injury/failure?

Answer 7

• Catabolic drugs (ex. steroids)
• GI/soft tissue bleeding
• Dietary protein intake

Question 8

When do you see an elevated serum creatinine for reasons OTHER than for kidney injury/failure?

Answer 8

• Increased muscle breakdown
• Various drugs

Also, baseline creatinine levels vary with muscle mass.

Question 9

Which drugs can lead to elevated CREATININE without true reduction in GFR? What is a good way to tell that the GFR is not affected in the setting of high creatinine?

Answer 9

• The antibiotic trimethoprim-sulfamethoxazole and the H2-blocker cimetidine are 2 commonly used drugs that decrease the secretion of creatinine. This can result in a self-limited and reversible increase in the serum creatinine level of as much as 0.4 to 0.5 mg/dL (depending on baseline serum creatinine level).
• Famotidine and ranitidine can likewise cause an increase but to a lesser degree.
• The antibiotic CEFOXTIN can spuriously increase the serum creatinine level by interfering with the colorimetric assay used to measure serum creatinine levels.

In both instances, the blood urea nitrogen (BUN) typically does not change. As such, an increase in creatinine level suggests a true decrease in GFR only if accompanied by a corresponding increase in BUN levels.

Question 10

Which patient characteristics will affect their baseline creatinine?

Answer 10

Age, sex, height, muscle mass, and limb amputation (this latter leads to significant reduction in muscle mass and thus lower baseline creatinine).

Question 11

Which values can you obtain from ordering a urine chemistry?

Answer 11

FENa, urine osmolality, urine Na+, urine Cr

Question 12

What is the etiology of prerenal acute renal failure?

Answer 12

Decrease in systemic arterial blood volume or renal perfusion, enough to lower the GFR, which leads to decreased clearance of metabolites.

• Hypovolemia (dehydration, excessive diuretic use, poor fluid intake, vomiting, diarrhea, burns hemorrhage)
• CHF (due to low CO)
• Hypotension (systolic < 90) from sepsis, anti-HTN meds, etc.
• Renal artery obstruction (kidney is hypoperfused despite elevated blood pressure)
• Cirrhosis, hepatorenal syndrome
• ALSO, in patients with decreased renal perfusion, NSAIDs (constrict afferent arteriole), ACE-Is (cause efferent arteriole vasodilation), and cyclosporin can precipitate prerenal failure.

Question 13

How does the kidney react in prerenal acute kidney injury?

Answer 13

APPRORIATELY! Since the renal parenchyma is unchanged, tubular function (and therefore concentrating ability) is prserved.

Theefore, the kidney thinks the body is hypovolemic and conserves as much Na+ and water as possible, AVIDLY!

This is why in prerenal causes of AKI, the FENa is <1% (low) - because we reabsorb Na+ to keep the water in, so Na+ excretion is low.

Question 14

In prerenal kidney failure, why is the BUN:Cr ration elevated (> 20:1)?

Answer 14

Since the renal parenchyma is unchanged, tubular function (and therefore reabsorption ability) is preserved. Therefore, the kidney can reabsorb urea (but Cr is never reabsorbed).

This leads to more BUN in serum than Cr.

Question 15

What does the serum creatinine and the urine creatinine do in prerenal AKI?

Answer 15

They both increase!

The serum [Cr] increases because filtration is decreased.

Urine [Cr] is incased because much of the filtrate (but not the creatinine) is avidly reabsorbed.

Question 16

Prerenal AKI =

Answer 16

Decrease in reenal blood flow

Question 17

Intrinsic AKI =

Answer 17

Damage to renal parenchyma

Question 18

Postrenal AKI =

Answer 18

Due to urinary tract obstruction of varying etiology

Question 20

Why is Na+ important for assessing the cause of acute kidney injury?

Answer 20

If the cause is PRERENAL, the kidney is being hypoperfused, but the renal parenchyma is still functional in its ability to reabsorb (i.e. Filtration is flow limited). Therefore the kidney avidly reabsorbs Na+ in order to to retain water and corrects what it perceives to be systemic hypovolemia (which may or may not be the case).
This makes FENa low ( 40 mEq/L).

Question 20

Which are the 4 main types of causes of intrinsic renal failure in acute kidney injury?

HINT: think of the major regions of the kidney/nephron

Answer 20

Think of the components/regions of the kidney and nephrons.

• Tubular disease (ATN) - caused by ischemia, nephrotoxins
• Glomerular disease (Acute glomerulonephritis) - Goodpasture’s, Wegener’s granulomatosis, post-streptococcal GN, lupus
• Vascular disease - renal artery occlusion (causes severe ischemia/ATN, but has a direct vascular cause), TTP, HUS (thrombosis and occlusion of renal vasculature)
• Interstitial disease - ex. allergic interstitial nephritis

Question 21

What is FENa? What two disease states does the value of FENa help you differentiate between?

Answer 21

Fractional excretion of sodium.

It is calculated based on the following formula:
FENa = (UrineNa / SerumNa) / (UrineCr / SerumCr) * 100

The FENa helps differentiate acute tubular necrosis from a prerenal state. FENa > 2 % usually indicates ATN (because Na+ reabsorption is poor), whereas FENa < 1% usually indicates a prerenal state such as dehydration or other forms of prerenal azotemia (because Na+ is avidly reabsorbed to conserve water).

FENa’s between 1% and 2% may be seen with either ATN or prerenal state.

Question 22

Which clinical feature is very different in prerenal vs. intrinsic AKI?

Answer 22

In PRERENAL, usually signs of volume depletion (dry mucous membranes, hypoTN, tachycardia, decreased tissue turgor/tenting, oliguria/anuria), whereas in INTRINSIC, edema is usually present.

Question 23

Rhabdomyolysis leads to elevated Cr, CPK. Does it cause prerenal or intrinsic renal failure?

Answer 23

INTRINSIC renal failure, because myoglobin is nephrotoxic and can lead to AKI and ATN.

Recall, rhabdomyolysis is skeletal muscle breakdown caused by: trauma, crush injuries, prolonged immobility, seizures, snake bites.

Lab findings: markedly elevated creatine phosphokinase (CPK) and creatinine, hyperkalemia, hypocalcemia, and hyperuricemia. THINK: serum elevation of the levels of classically intracelluar ions because when the muscle cells break down they lyse and release their contents.

How do you manage? Tx with IV fluids, mannitol (osmotic diuretic)” and bicarb (to drive K+ back into cells - deviations in serum K+ are BAD, can cause deadly arrhythmias either way)

Question 24

Mechanism of ischemic AKI causing ATN

Answer 24

Secondary to severe decline in renal blood flow, as in shock, hemorrhage, sepsis, DIC, and heart failure.

Ischemia results in DEATH of tubular cells. RIP.

Question 25

Mechanism of nephrotoxic AKI causing ATN.

Who are major offendors?

Answer 25

Tubular injury secondary to substances that directly injure the rernal parenchyma and result in cell death.

Major offendors? Think CHIP MAN (as in death)

Chemotherapeutic agents (cisplatin) AND (radio)Contrast
Hemoglobinuria (from hemolysis)
Immunoglobulins (kappa and gamma light chains, mult myeloma)
Poisons

Myoglobinuria (muscle breakdown, rhabdo, cross-fit)
Antibiotics (aminoglycosides, VANCO)
NSAIDs (esp. in the setting of CHF)

Question 26

What symptoms does the patient with AKI usually exhibit?

Answer 26

None! The diagnosis of AKI is usually made by finding elevated BUN + Cr levels. The patient is usually asymptomatic.

Think of how this might be a common incidental findings in inpatients who are getting routine labs because they are likely to suffer hypovolemia/severe hypoperfusion, they get contrast, vanco, and NSAIDs, etc. They are very sick, and we may also injure their kidneys iatrogenically.

Question 27

What are three basic ways to test for post-renal acute kidney failure?

Answer 27

Physical examination - palpate the bladder
US - look for obstuction, hydronephrosis
Catheter- look for large volume of urine upon insertion

See, nothing too fancy!

Question 28

Which is the most common cause of acute kidney injury?

Answer 28

Prerenal (60-70%) > Intrinsic (25-40%) > Postrenal (less common, 5-10%)

Question 29

What happens to BUN in intrinsic renal failure?

Answer 29

There is decreased BUN/serum creatinine ration (t get me wrong, BOTH BUN and serum creatinine are still elevated in both prerenal and intrinsic renal failure. However, in the later, less urea is absorbed, so the increase in BUN does not outstrip that of Cr by as much.
At

Question 30

Laboratory signs of INTRINSIC renal failure all display a common theme, inability to reabsorb ions/solutes and poor concentrating ability of the tubule. Therefore, what do you typically see?

Answer 30

Decreased BUN-serum creatinine ratio (40mEq/L)
Increased FENa (>2-3%>)
Decreased urine osmolality (<20:1) because the filtrate cannot be reabsorbed.

Question 31

What is the common theme behind postrenal AKI?

Answer 31

OBSTRUCTION! Of any segment of the urinary tract with intact kidney.

This causes increased tubular pressur because the urine produced cannot be excreted, leading to decreased GFR.

Renal function is restored if the obstruction is relieved before the kidneys are damaged. If untreated, can lead to ATN (intrinsic AKI ).

Question 32

What is the most common cause of postrenal AKI?

Answer 32

Urethral obstruction due to BPH.

Other: nephrolithiasis, obstructing neoplasm, retroperitoneal fibrosis.

Question 33

Urine osmolality (measure of urine concentration) is HIGH in volume deplete states (when ADH stimulates H2O reabsorption) and LOW in ATN, where tubule cells cannot reabsorb water (or sodium) and concentrating ability is lost.

Answer 33

‘Nuff said.

Question 34

What is the most important thing in medical school and residency?

Answer 34

Always maintain a positive outlook (and an avidity for learning!).

Question 35

Which labs should you order in a patient with AKI? Give rationale.

Answer 35

• Urinalysis - protein + dipstick is sign of glomerular insult, microscopic examination is useful.
• Serum electrolytes - look for elevation in serum Cr and BUN, as well as Na+ and K+ levels
• CBC
• Urine chemistry - gives you urine Na+, Cr, and osmolality, allows you to distinguish between forms of AKI (however, recall that urine Na+ depends on dietary intake)
• Urine cultures and sensitivity, if infection suspected (esp. based on urine dip)
• Bladder catheterization (rule out obstruction, Dx and Rx)
• Renal ultrasound to look for obstruction (unless cause is obvious and not postrenal)

If you collect urine and plasma electrolytes at the same time, can get FENa! This is usually most useful if oliguria is present.

Other, more advanced testing in includes: CT abdomen/pelvis, renal biopsy, and renal arteriography (perform only if specific therapy will make a difference, consider that it involves contrast which is nephrotoxic).

Question 36

What should be your approach to evaluating a patient with AKI?

Answer 36

First, exclude prerenal and post-renal causes, and them, if necessary, investigate intrinsic renal causes if necessary.

Exclude postrenal with Foley, US.

If urinalysis is benign, consider prerenal causes. Although may be intrinsic.

If urinalysis not benign, you’re probably stuck with intrinsic causes such as ATN, glomerular disee, and pyeloneprhitis or acute interstitial nephritis.

Question 37

What the hell does UREMIA stand for? What are the symptoms of uremia?

Answer 37

Refers to the signs and symptoms associated with accumulation of toxic end products in the serum (especially those from protein metabolism), particularly UREA and other nitrogrenous waste, due to impaired renal function.

It is difficult to predict when uremic symptoms will apppear, but it rarely occurs unless BUN >60mg.

When enough of these waste products accumulate, the uremia becomes symptomatic. Early symptoms include anorexia and lethargy, and late symptoms can include decreased mental acuity and coma. Other symptoms include fatigue, nausea, vomiting, cold, bone pain, itch, shortness of breath, and seizures

Symptoms can be broken down into categories:

• Neural and muscular: Decreased mental acuity, seizures, anorexia, weakness, decreased taste and smell, cramps, restless legs, sleep disturbance, coma, encephalopathy
• Endocrine and metabolic: reduced body temp, altered AA levels, bone disease (due to hypoposphatemia, hyperparathyroidism, or vitD deficiency), reduced basal metabolic rate, insulin resistance, increased muscle protein catabolism.
• Other: sclerositis (including pericarditis), itching/pruritus, hiccups. oxidative stress, granylocyte ad lymphocyte dysfunction, platelet dysfunction, excretion of retained urea through the skin with subsequent crystalization leading to characteristic “uremic frost”.

Question 38

How do you manage AKI?

Answer 38

1. Avoid medications that decrease renal blood flow (NSAIDS) and/or are nephrotoxic (aminoglycosides, contrast).
2. Adjust meds for level of renal func.
3. Correct fluid imbalance: may involve IV fluid administration or diuresis. The goal is to strike the balance between correcting volume deficits and preventing volume overload while mainaining an adequate urine output. Must monitor fld balance with daily weights (most accurate) as well as I/O records. Make sure to take cardiac history (i.e. CHF!) into account when making fluid decisions .
4. Correct electrolyte disturbances if present
5. Optimize cardiac output (BP should be approx 120-140/80)
6. Order dialysis if symptomatic IF symptomatic uremia, intractable acidemia, hyperkalemia, or volume overload develop.

Question 39

When would you order dialysis for a patient with acute kidney injury/renal failure?

Answer 39

In the setting of:

• symptomatic uremia
• intractable acidemia
• hyperkalemia
• volume overload

Question 40

How can radiographic contrast cause ATN?

Answer 40

By causing a spasm of the afferent arteriole. Can be prevented with saline hydration.

(This happens typically very rapidly)

Question 41

Which clinical, laboratory, and imaging features favor chronic kidney disease (as opposed to acute)?

Answer 41

• History of kidney disease, HTN, abnormal urinalysis, edema.
• Small kidney size on US
• HyperK, acidemia, hyperphosphatemia (kidney not excreting these well, so they accumulate in serum)
• Anemia (recal, kidneys produce EPO!)
• Urinalysis with broad casts (ex. > 2-3 WBCs in diameter.

Question 42

Which clinical and laboratory features favor acute kidney disease (as opposed to chronic)?

Answer 42

Return of renal function to normal with time
Hyperkalemia, acidemia, hyperphosphatemia, anemia
UOP <500mL/day without uremic symptoms

Question 43

What is the first thing you do when a person has elevated Cr levels?

Answer 43

Determine what their BASELINE creatinine is, if possible. This helps determine whether the patient has AKI, CKD, or chronic renal insufficiency/failure with SUPERIMPOSED AKI (i.e. “acute on chronic” renal failure.

Question 44

How do you define ESRD? What are the most common causes of ESRD?

Answer 44

ESRD is defined as a loss of kidney function that lead to clinical and laboratory findings of uremia. It is NOT defined by any particular BUN/creatinine levels (as compared to other electrolyte imbalances syndromes like the -natremias, which are defined by certain levels).

The most common causes are diabetes (30%) and HTN (25%), aka the root of all evil. Less common causes include chronic GN, interstitial nephritis, polycystic kidney disease, obstructive uropathy, and any of the causes of AKI if prolonged and/or treatment is delayed.

Question 45

When a patient’s renal function is irreversibly compromised but NOT failed, the term CHRONIC RENAL INSUFFICIENCY is used. Who does this classification generally apply to?

Answer 45

Those with chronic elevation of serum creatinine to 1.5 to 3.0 mg/dL.

Question 46

In patients with CKD, what are the two most common complications that require urgent intervention?

Answer 46

Symptomatic volume overload (including lulmonary edema)
Severe hyperkalemia

(Also, infection)

Question 47

Management of CKD includes…

Answer 47

1. Diet
2. ACE inhibitors (dilate efferent artery of glomerulus) - if used early on, may slow the progression of proteinuria (although CAUTION, may cause hyperK)
3. BP control -strict control decreases the rate of disease progression. ACE-Is are preferred agents, but multiple agents may be necessary.
4. Glycemic control (if diabetic)
5. Smoking cessation
6. Correction of electrolyte abnormalities
7. Anemia - treat with erythropoietin
8. Pulmonary edema - arrange for dialysis if unresponsive to diuresis
9. Pruritus - try capsaicin cream or choletyramine, and UV light
10. Dialysis
11. Transplantation is the only cure

Question 48

Absolute indications for dialysis = AEIOU

Answer 48

Acidosis - significant, intractable metabolic acidosis
Electrolytes - severe, persistent hyperK
Intoxications - with methanol, ethylene glycol, lithium, aspirin
Overload - hypervolemia not managed by other means
Uremia (severe) - basrd on clinical presentation, not lab values

Question 49

How do you reverse someone on Coumadin?

Answer 49

Give IV Vitamin K. Usually, small doses repeated if necessary are best ( if you give a very high dose from the outset, you may then find it hard to return to therapeutic anticoagulant effect when restarting Coumadin)

FFP may also be given in persons at risk of serious bleeding (replaces the vitK dependent clotting factors that cannot get produced on Coumadin)

Question 50

What is the pharmacological mechanism of action of Coumadin/warfarin?

Answer 50

Inhibit vitamin K epoxide reductase, the enzyme that recycles oxidized vitK to it’s reduced form after it has participated in the carboxylation of several blood coagulation proteins, mainly prothrombin and factor VII.

Despite being labeled a vitK antagonist, warfarin does NOT antagonize the action of vitamin K1. RATHER, it antagonizes vitamin K1 recycling, this depleting active vitamin K1.

This is why the pharmacologic action of warfarin may always be reversed by fresh VitK.

Question 51

What is vasovagal syncope (aka reflex syncope, aka neurocardiogenic syncope)?

Answer 51

Vasovagal (neurocardiogenic) syncope (also known as the “common faint”) refers to a variety of clinical scenarios in which a neural reflex results in usually self-limited systemic HYPOTENSION characterized by BRADYCADRIA and/or peripheral VASODILATION. The hypotension can lead to cerebral HYPOPERFUSION, and sudden/transient LOC.

Vasovagal syncope is often associated with a PRODROME and persistence of nausea, pallor, and diaphoresis, consistent with increased VAGAL tone. Syncope is typically of short duration and occurs in the sitting or standing position. The SUPINE position restores adequate blood flow to the brain. However, full recovery may be delayed as the patient may feel depressed or fatigued. This course may help distinguish vasovagal syncope from syncope associated with arrhythmia, which is typically of abrupt onset and of short duration. Loss of consciousness may be prolonged with some other causes of syncope, such as seizures and aortic stenosis, but rarely with vasovagal syncope.

Question 52

Describe the neuronal patway that mediates vasovagal/neurocardiogenic syncope?

Answer 52

It may be mediated by a CARDIOINHIBITORY and/or VASODEPRESSOR response. In it, the nucleus tractus solitarii (nucleus of the solitary tract) of the brainstem is activated directly or indirectly by the triggering stimulus, resulting in simultaneous enhancement of parasympathetic nervous system (VAGAL) tone and withdrawal of sympathetic nervous system tone.

Cardioinhibitory response: results from increased PARASYMPATHETIC activation and may be manifested by any or all of the following: sinus bradycardia, asystole, PR prolongation, and advanced atrioventricular block.

Vasodepressor response: due to inhibition of (decreased) SYMPATHETIC activity and can lead to hypotension. Reduced cardiopulmonary baroreceptor sensitivity may be a contributing factor