8/10/2007

Objectives
Emergencies in nephrology: hyperkalemia
What you really need to know to hyponatremia
survive a night of call! acute renal failure
rapidly
idl progressive
i glomerulonephritis
l l h iti
malignant hypertension
Dr. Sandra Cockfield
University of Alberta

Hyperkalemia Clinical features of hyperkalemia

serum K+ > 5.0 mmol/L
normal renal response to hyperkalemia should be to
stimulate secretion of aldosterone which in turn should
stimulate urinary K excretion
urinary K+ excretion should be high, ideally > 100
mmol/d
trans-tubular potassium gradient should be > 7
skeletal muscle weakness, paralysis, respiratory
failure
EKG abnormalities (progress from peaked T waves
prolonged PR interval and ST depression wide
QRS with sine wave pattern (intraventricular block)
ventricular fibrillation

Potassium Questions to ask in hyperkalemia

1. Is there a reason for K to have shifted from the
ICFV?
ICF ECF
3 Na+ 2. Did the K shift occur after the blood was collected?
Na = 10 mmol/L Na = 150 mmol/L
3 Are the kidneys excreting K appropriately?
3.
K = 140 mmol/L 2 K+ K = 4 mmol/L
4. If the kidneys are not excreting K, why not?
5. Is dietary K intake excessive, contributing to the
problem?
K+ flux across the cell membrane is a major determinant
of the membrane potential. Patients with abnormalities
of serum K+ present with disorders of neuromuscular
function.

1
 8/10/2007

K+ shifts between fluid compartments Questions to ask in hyperkalemia

ECF 1. Is there a reason for K to have shifted from the
beta2 adrenergics ICFV?
insulin
K+ 2. Did the K shift occur after the blood was collected?
alkalosis (H+ K+)
anabolism 3 Are the kidneys excreting K appropriately?
3.
ICF 4. If the kidneys are not excreting K, why not?
alpha adrenergics
5. Is dietary K intake excessive, contributing to the
K+ acidosis (K+ H +) problem?
cellular necrosis
catabolism

cell necrosis HYPERKALEMIA

burns
rhabdomyolysis before after collection Questions to ask in hyperkalemia
insulin lack ?K shift out of cells
acidosis collection
hemolysis (during collection) 1. Is there a reason for K to have shifted from the
B blocker
no
thrombocytosis (>106) ICFV?
leukocytosis (>105)
2. Did the K shift occur after the blood was collected?

hi h
high l
low 3 Are the kidneys excreting K appropriately?
3.
dietary excess ?urine K excretion
cell necrosis 4. If the kidneys are not excreting K, why not?
renal failure 5. Is dietary K intake excessive, contributing to the
severe ECFV contraction
problem?
aldosterone deficiency
aldosterone resistance
K sparing diuretics
ACE inhibitors
ARBs

Questions to ask in hyperkalemia

+ hyperkalemia
1. Is there a reason for K to have shifted from the
ICFV?
2. Did the K shift occur after the blood was collected?
3 Are the kidneys excreting K appropriately?
3.
4. If the kidneys are not excreting K, why not?
5. Is dietary K intake excessive, contributing to the
problem?

Kidney failure is
the leading
cause of severe
hyperkalemia

Palmer B. N Engl J Med 2004;351:585-592

2
 8/10/2007

Treatment of hyperkalemia
severe hyperkalemia with EKG changes is life-
threatening due to the risk of ventricular arrhythmias
do an urgent EKG and a repeat serum K+
if the EKG shows evidence of hyperkalemia,
yp , start
treatment immediately without waiting for laboratory
confirmation of hyperkalemia

Gennari F. N Engl J Med 1998;339:451-458

The effect of disorders of [K+] on cell

membrane potential
Treatment of hyperkalemia
stop K+ intake (iv, po, meds)
antagonize the effects of hyperkalemia on the mV
myocardium with 10 ml of 10% calcium gluconate over 1
minute. Will not lower [K+] but will stabilize the heart
calcium
administration

E threshold

E resting
hyperK
hypoK

Treatment of hyperkalemia Shifting potassium

stop K+ intake (iv, po, meds)
antagonize the effects of hyperkalemia on the
myocardium with 10 ml of 10% calcium gluconate over 1
minute. Will not lower [K+] but will stabilize the heart
shift K+ into the cell
10 U iv insulin + 1 amp 50% dextrose (15 mins)
high dose beta agonist (30 minutes)
serum bicarbonate (weakest, 3-4 hours to work;
of most utility in acidotic patients)

3
 8/10/2007

Treatment of hyperkalemia
stop K+ intake (iv, po, meds)
antagonize the effects of hyperkalemia on the
myocardium with 10 ml of 10% calcium gluconate over 1
minute. Will not lower [K+] but will stabilize the heart
shift K+ into the cell
remove K+
-loop diuretics (only if good kidney function)
-kayexalate (exchange resin binds K in the gut;
30-50 g po q 2-4 hours; oral superior to rectal;
consider risk of ischemic gut with high doses)
-hemodialysis (for patients with renal failure)
Alfonso et al, Resuscitation
2006; 70:10-25

Hyponatremia

serum sodium < 135 mmol/L

usually associated with decreased serum osmolality
usually due to relative water excess diluting Na+
appropriate response should be to inhibit the
secretion of ADH, reducing H2O reabsorption in the
collecting duct H2O loss from the body
all patients with hyponatremia should excrete a
maximally dilute urine (urine osmolality of 50-100
mosm/kg, SG < 1.005)
failure to do so suggests that ADH is still acting

Exceptions:
Serum osmolality = 2(Na+ + K+) + [urea] + [glucose]
1. Hyperosmolar hyponatremia:
= 2(140 + 4) + 6 + 6
hyponatremia associated with hyperglycemia
= 300 mosm/kg
if glucose can not enter the cell due to insulin
deficiency, glucose becomes an effective osmole in the
deficiency
The majority of cases of hyponatremia are ECFV H2O moves from the ICFV to dilute the ECFV
associated with a low serum osmolality due to the [Na+]
dominant effect of serum [Na+] on this equation. for every 10 mmol/L rise in serum glucose above 10
mmol/L, the serum [Na+] will fall by ~3 mmol/L
Rx of the hyperglycemia allows H2O to shift back to the
ICFV

ICFV = intracellular fluid volume; ECFV = extracellular fluid volume

4
 8/10/2007

ECFV or effective
Exceptions: The ADH axis circulating volume

2. Factitious hyponatremia: ECFV hypothalmus - pain, nausea

osmolality posterior pituitary
hyponatremia associated with normal serum drugs
osmolality
due to a laboratory artifact created when the solid CNS disease
fraction of plasma rises above the normal 7% due
to hyperlipidemia or hyperproteinemia
ADH secretion
of historical interest only as newer laboratory
techniques avoid this problem exogenous ADH

H2O reabsorption potentiated ADH action

in collecting duct

hyponatremia

high N
Syndrome of inappropriate ADH
hyperglycemia plasma osmolality? factitious
low
low
not low diagnosis of exclusion
volume (Na+) loss ECFV? effective circulating
gut volume? rule out ECFV contraction, renal failure, thiazides,
skin low
hypothyroidism, and hypoadrenalism
not low
kidneys water ingestion CHF 1 CNS source: CNS disease (#
1. (#, subdural
subdural,CVA,
CVA infection)
thiazides (diluting ability) cirrhosis drugs (narcotics, vincristine)
SIADH nephrosis metabolic disorders (porphyria)
hypoalbuminemia
2. Exogenous: pulmonary (TB, sarcoid, abscess)
hypothyroidism
neoplastic (oat cell CA, pancreatic CA)
hypoadrenalism
administered (ADH, oxytocin)
> serum
<100 osmolality 3. Drugs potentiating ADH action (chlorpropamide,
water ingestion urine osmolality? SIADH
aminophylline)

Questions to ask in a case of hyponatremia Symptoms of hyponatremia

1. What is the serum osmolality?

depends on rapidity of fall in [Na+] and severity of
hyponatremia
2. What is the ECFV? the effective circulating volume?
nausea, anorexia, malaise, headache, lethargy
3. What is the renal response to the hyponatremia?
seizures,
seizures coma
coma, and death (cerebral edema)
4. If the urine is not maximally dilute, why not? Is there
a physiologic reason that ADH may be present? H2O

5. What are the clinical consequences of the

hyponatremia in this patient? ICFV ICFV

acute
hyponatremia
SYMPTOMS

5
 8/10/2007

Acute hyponatremia:
Symptoms of hyponatremia
- rare situation; always occurs within 24hrs of surgery
- potentially lethal (most dangerous!) depends on rapidity of fall in [Na+] and severity of
- correct quickly and fully with hypertonic saline lasix hyponatremia
nausea, anorexia, malaise, headache, lethargy
seizures,
seizures coma
coma, and death (cerebral edema)
osmoles
H2O and
H2O

ICFV ICFV ICFV

acute chronic
hyponatremia hyponatremia
SYMPTOMS

The treatment of hyponatremia: insufficient too aggressive

correction correction
symptomatic hyponatremia is a medical emergency
consider both the severity and rapidity of the
hyponatremia cerebral edema osmotic demyelinating
y
syndrome
hyponatremia which arose over > 24 hours should be
treated slowly; acute hyponatremia developing over < 24
hours must be corrected quickly and fully
DO NOT OVER-CORRECT

Osmotic demyelination syndrome The treatment of hyponatremia:

aka central pontine myelinolysis STOP WATER INTAKE; fluid restrict to 1 L/day
best described in setting of rapid correction of chronic treat the underlying cause (CHF, volume contraction,
hyponatremia nausea, pain, hormone deficiencies, drugs)
increased risk if hypokalemic
hypokalemic, malnourished
malnourished, or hypertonic saline (3% saline = [Na+] of 513 mmol/L)
alcoholic loop diuretic to encourage excretion of the Na+ (and
typically present days later with spastic H2O) as the large Na+ load with this iv solution can
quadraparesis, pseudobulbar palsies, decreasing level result in pulmonary edema
of consciousness SIADH - antagonize ADH using demeclocycline or
permanent CNS deficits, possible death lithium to induce nephrogenic diabetes insipidus

6
 8/10/2007

Acute hyponatremia:
- rare situation; always occurs within 24hrs of surgery
- potentially lethal (most dangerous!)
- correct quickly and fully with hypertonic saline lasix
Asymptomatic hyponatremia (usually chronic):
- fluid restrict
restrict, treat underlying cause
- correct over days
Symptomatic chronic hyponatremia:
- correct with fluid restriction and hypertonic saline
- aim for correction rate of 0.5 - 1.0 mmol/L/hr
- correct no more than 12-15 mmol/L in 24 hours
- monitor serum [Na+] q2-4 hours and adjust therapy
- DO NOT OVERCORRECT!

What is your differential diagnosis?

Acute renal failure Urgent issues in acute renal failure
Pre-renal Post-renal need to treat life threatening complications
risk factors lower urinary tract 9 volume overload
symptoms/signs or
small volume of abdominal pain 9 hyperkalemia
concentrated urine
(uNa<20 mM, FENa<1%) obstruction may reversibility with volume resuscitation (prevent pre-
Renal respond to insertion of a
no structural damage catheter renal from becoming ATN)
responds quickly to R/O pre and post-renal
correction of underlying glomerular (RPGN)
abdominal US shows catheterize if oligoanuric
hydronephrosis
problem (CVP and BP)
tubulointerstitial (ATN, re-establish urine output with volume accelerating
AIN, myeloma kidney)
vascular (malignant doses of furosemide (40, 80, 160 mg iv)
HTN, HUS/TTP,
vasculitis, thrombosis) diagnostic urgency
9 rapidly progressive glomerulonephritis (RPGN)
9 thrombotic microangiopathy (HUS/TTP)
FENa = [urine Na]/[plasma Na] x 100
[urine creatinine]/plasma creatinine]
9 malignant hypertension

Approach to acute renal failure

Differential diagnosis of anuria
careful history: acute obstruction
9 lower urinary tract symptoms
9 change in urine output, urine appearance abnormal
RPGN
9 symptoms of uremia (acute vs. chronic) severe ATN or cortical necrosis
9 symptoms of a systemic illness
9 drug/toxin history; recent contact with physicians myeloma
l kid
kidney ((usually
ll nott anuric)
i )
physical examination emphasizing BP, JVP, arterial occlusion
assessment of fluid status and evidence of a systemic
illness (fever, wt loss, rash, arthritis, sinusitis,
pneumonia, CNS findings)
catheterize if oliguric
volume resuscitate, aim for JVP 3-4 cm > sternal angle

7
 8/10/2007

Approach to acute renal failure Renal causes of ARF

URINALYSIS; abnormal in > 90% of cases of ARF glomerular:
due to renal parenchymal disease RPGN immune complex (SLE, SBE, HSP...)
a normal urinalysis would suggest a limited pauci-immune (vasculitides)
differential (pre-renal, post-renal, hypercalcemia, anti-GBM (Goodpastures syndrome)
multiple
lti l myeloma,
l atheroembolic
th b li di
disease)) urinalysis U protein/creatinine,
urinalysis, protein/creatinine serology
serology, CXR
CXR, Bx

specific abnormalities in the urinalysis may suggest tubulointerstitial:

a specific category of disease ATN (ischemic, toxic)
acute interstitial nephritis
SERUM AND URINE ELECTROLYTES cast nephropathy (myeloma, rhabdo, drugs)
URINE PROTEIN/CREATININE RATIO metabolic (hypercalcemia, tumor lysis...)
history, urinalysis, CBC, lytes (tubular defects),
SERUM CREATININE serum calcium, SPEP, Bx
PAST LABORATORY VALUES

Rapidly progressive glomerulonephritis

acute glomerulonephritis, pulmonary-renal syndromes,
systemic diseases (ie. lupus, vasculitis)
U/A > 2+ proteinuria, U protein/creatinine ratio > 200
mg/mmol; micro- or macro-hematuria, RBC casts
if creatinine rapidly rising, this is a medical emergency
prognosis is often dependent upon when therapy is
initiated (especially true for anti-GBM disease)
usually requires a renal biopsy for specific diagnosis
treatment should be initiated once RPGN is suspected
- pulse methylprednisolone 1 g iv daily x 3 days
- do not wait for biopsy confirmation

Malignant or accelerated hypertension Malignant or accelerated hypertension

life-threatening
usually acute rise in BP to values > 180/120 mmHg
associated with retinal hemorrhages, exudates, and
papilledema
associated with headache, nausea, vomiting, CNS
findings (lacunar infarcts, intracerebral bleed, cortical
blindness), seizures, coma and death
acute renal failure due to thrombotic microangiopathy
MUST BE MANAGED IN CRITICAL CARE AREA
where intensive monitoring is available
will require initiation of parenteral anti-hypertensive
therapy
9 nitroprusside 0.25-0.5 g/kg/min titrated up to 10 g/kg/min
9 labetolol 20 mg iv, then 20-80 mg iv q10min to maximum of
300 mg or 00.5
5-2
2 mg/min continuous iv
9 other agents may be indicated in special circumstances (ie.
pre-eclampsia, coronary ischemia, aortic dissection)
dose titration to achieve BP of ~160/100 initially
switch to oral therapy once initial control established
slowly bring BP toward 140/90 mmHg over the next 2-
3 months

8
 8/10/2007

Hypertensive emergencies
Accelerated-malignant hypertension with papilloedema
Cerebrovascular
Hypertensive encephalopathy
Atherothrombotic brain infarction with severe hypertension
Intracerebral hemorrhage
Subarachnoid hemorrhage
Cardiac
Acute aortic dissection
Acute left ventricular failure
Acute or impending myocardial infarction
After coronary bypass surgery
Renal
Acute glomerulonephritis
Renal crises from collagen vascular diseases (i.e. scleroderma)
Severe hypertension after kidney transplantation
Excessive circulating catecholamines
Pheochromocytoma crisis
Food or drug interactions with monoamine-oxidase inhibitors
Sympathomimetic drug use (cocaine)
Rebound hypertension after sudden cessation of antihypertensive drugs
Eclampsia
Surgical
Severe hypertension in patients requiring immediate surgery
Postoperative hypertension
Postoperative bleeding from vascular suture lines